FN Thomson Reuters Web of Science™ VR 1.0 PT J AU House, CD Annunziata, CM AF House, Carrie D. Annunziata, Christina M. TI Dissecting the role of NF-kappaB signaling in ovarian cancer tumor-initiating cells. SO CLINICAL CANCER RESEARCH LA English DT Meeting Abstract CT AACR Special Conference on Advances in Ovarian Cancer Research - Exploiting Vulnerabilities CY OCT 17-20, 2015 CL Orlando, FL SP Amer Assoc Canc Res C1 [House, Carrie D.; Annunziata, Christina M.] NCI, Bethesda, MD 20892 USA. RI Annunziata, Christina/L-3219-2016 OI Annunziata, Christina/0000-0003-2033-6532 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 JAN 15 PY 2016 VL 22 SU 2 MA A72 PG 1 WC Oncology SC Oncology GA DI2QU UT WOS:000373342300059 ER PT J AU Toriola, AT Keogan, K Morrison, L Pollack, L Gerhlert, S Park, Y Brinton, L AF Toriola, Adetunji T. Keogan, Kathleen Morrison, Leavitt Pollack, Lisa Gerhlert, Sara Park, Yikyung Brinton, Louise TI Pre-diagnosis adiposity, physical activity, and ovarian cancer survival. SO CLINICAL CANCER RESEARCH LA English DT Meeting Abstract CT AACR Special Conference on Advances in Ovarian Cancer Research - Exploiting Vulnerabilities CY OCT 17-20, 2015 CL Orlando, FL SP Amer Assoc Canc Res C1 [Toriola, Adetunji T.; Keogan, Kathleen; Morrison, Leavitt; Pollack, Lisa; Gerhlert, Sara; Park, Yikyung] Washington Univ, Sch Med, St Louis, MO USA. [Brinton, Louise] 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 JAN 15 PY 2016 VL 22 SU 2 MA PR11 PG 2 WC Oncology SC Oncology GA DI2QU UT WOS:000373342300164 ER PT J AU Kim, EH Wang, B Sastry, N Masliah, E Nelson, PT Cai, HB Liao, FF AF Kim, Eunhee Wang, Bin Sastry, Namratha Masliah, Eliezer Nelson, Peter T. Cai, Huaibin Liao, Francesca-Fang TI NEDD4-mediated HSF1 degradation underlies alpha-synucleinopathy SO HUMAN MOLECULAR GENETICS LA English DT Article ID SHOCK TRANSCRIPTION FACTOR-1; MOLECULAR CHAPERONES; UBIQUITIN LIGASE; SACCHAROMYCES-CEREVISIAE; HEAT-STRESS; CROSS-TALK; DISEASE; NEURODEGENERATION; ACETYLATION; TOXICITY AB Cellular protein homeostasis is achieved by a delicate network of molecular chaperones and various proteolytic processes such as ubiquitin-proteasome system (UPS) to avoid a build-up of misfolded protein aggregates. The latter is a common denominator of neurodegeneration. Neurons are found to be particularly vulnerable to toxic stress from aggregation-prone proteins such as alpha-synuclein. Induction of heat-shock proteins (HSPs), such as through activated heat shock transcription factor 1 (HSF1) via Hsp90 inhibition, is being investigated as a therapeutic option for proteinopathic diseases. HSF1 is a master stress-protective transcription factor which activates genes encoding protein chaperones (e.g. iHsp70) and anti-apoptotic proteins. However, whether and how HSF1 is dysregulated during neurodegeneration has not been studied. Here, we discover aberrant HSF1 degradation by aggregated alpha-synuclein (or alpha-synuclein-induced proteotoxic stress) in transfected neuroblastoma cells. HSF1 dysregulation via alpha-synucleinwas confirmed by in vivo assessment of mouse and in situ studies of human specimens with alpha-synucleinopathy. We demonstrate that elevated NEDD4 is implicated as the responsible ubiquitin E3 ligase for HSF1 degradation through UPS. Furthermore, pharmacologically induced SIRT1-mediated deacetylation can attenuate aberrant NEDD4-mediated HSF1 degradation. Indeed, we define the acetylation status of the Lys 80 residue located in the DNA-binding domain of HSF1 as a critical factor in modulating HSF1 protein stability in addition to its previously identified role in the transcriptional activity. Together with the finding that preserving HSF1 can alleviate alpha-synuclein toxicity, this study strongly suggests that aberrant HSF1 degradation is a key neurodegenerative mechanism underlying alpha-synucleinopathy. C1 [Kim, Eunhee; Wang, Bin; Liao, Francesca-Fang] Univ Tennessee, Ctr Hlth Sci, Dept Pharmacol, 874 Union Ave Crowe 401, Memphis, TN 38163 USA. [Kim, Eunhee; Wang, Bin; Liao, Francesca-Fang] Univ Tennessee, Ctr Hlth Sci, Dept Anat & Neurobiol, 874 Union Ave Crowe 401, Memphis, TN 38163 USA. [Sastry, Namratha; Cai, Huaibin] NIA, Transgen Sect, NIH, Bethesda, MD 20892 USA. [Nelson, Peter T.] Sanders Brown Ctr Aging, Dept Neurol, 800 South Limestone St, Lexington, KY 40536 USA. [Masliah, Eliezer] Univ Calif San Diego, Dept Neurosci, La Jolla, CA 92093 USA. RP Liao, FF (reprint author), UTHSC, Dept Pharmacol, 874 Union Ave,Crowe Bldg 401, Memphis, TN 38163 USA. EM fliao@uthsc.edu RI WANG, BIN/K-3986-2015 OI WANG, BIN/0000-0001-9032-5009 FU NIH [R01 AG031893, R21 AG041934, R21 NS083908, R37 AG18440, R21 NS085830, P30 AG028383, AG049772]; Alzheimer Association [IIRG-11-204040]; NIH intramural research program [AG000929] FX This work was supported by NIH grants R01 AG031893, R21 AG041934, R21 NS083908 to F.F.L, R37 AG18440 to E.M., R21 NS085830, P30 AG028383 to P.T.N., by Alzheimer Association grant IIRG-11-204040 to F.F.L. and by NIH intramural research program AG000929 to H.-B.C. Funding to pay the Open Access publication charges for this article was provided by NIH grant AG049772 to F.F.L. NR 36 TC 4 Z9 4 U1 2 U2 3 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0964-6906 EI 1460-2083 J9 HUM MOL GENET JI Hum. Mol. Genet. PD JAN 15 PY 2016 VL 25 IS 2 BP 211 EP 222 DI 10.1093/hmg/ddv445 PG 12 WC Biochemistry & Molecular Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Genetics & Heredity GA DG5VU UT WOS:000372148200001 PM 26503960 ER PT J AU de Vries, PS Chasman, DI Sabater-Lleal, M Chen, MH Huffman, JE Steri, M Tang, WH Teumer, A Marioni, RE Grossmann, V Hottenga, JJ Trompet, S Muller-Nurasyid, M Zhao, JH Brody, JA Kleber, ME Guo, XQ Wang, JJ Auer, PL Attia, JR Yanek, LR Ahluwalia, TS Lahti, J Venturini, C Tanaka, T Bielak, LF Joshi, PK Rocanin-Arjo, A Kolcic, I Navarro, P Rose, LM Oldmeadow, C Riess, H Mazur, J Basu, S Goel, A Yang, Q Ghanbari, M Willemsen, G Rumley, A Fiorillo, E de Craen, AJM Grotevendt, A Scott, R Taylor, KD Delgado, GE Yao, J Kifley, A Kooperberg, C Qayyum, R Lopez, LM Berentzen, TL Raikkonen, K Mangino, M Bandinelli, S Peyser, PA Wild, S Tregouet, DA Wright, AF Marten, J Zemunik, T Morrison, AC Sennblad, B Tofler, G de Maat, MPM de Geus, EJC Lowe, GD Zoledziewska, M Sattar, N Binder, H Volker, U Waldenberger, M Khaw, KT Mcknight, B Huang, J Jenny, NS Holliday, EG Qi, LH Mcevoy, MG Becker, DM Starr, JM Sarin, AP Hysi, PG Hernandez, DG Jhun, MA Campbell, H Hamsten, A Rivadeneira, F Mcardle, WL Slagboom, PE Zeller, T Koenig, W Psaty, BM Haritunians, T Liu, JM Palotie, A Uitterlinden, AG Stott, DJ Hofman, A Franco, OH Polasek, O Rudan, I Morange, PE Wilson, JF Kardia, SLR Ferrucci, L Spector, TD Eriksson, JG Hansen, T Deary, IJ Becker, LC Scott, RJ Mitchell, P Marz, W Wareham, NJ Peters, A Greinacher, A Wild, PS Jukema, JW Boomsma, DI Hayward, C Cucca, F Tracy, R Watkins, H Reiner, AP Folsom, AR Ridker, PM O'Donnell, CJ Smith, NL Strachan, DP Dehghan, A AF de Vries, Paul S. Chasman, Daniel I. Sabater-Lleal, Maria Chen, Ming-Huei Huffman, Jennifer E. Steri, Maristella Tang, Weihong Teumer, Alexander Marioni, Riccardo E. Grossmann, Vera Hottenga, Jouke J. Trompet, Stella Mueller-Nurasyid, Martina Zhao, Jing Hua Brody, Jennifer A. Kleber, Marcus E. Guo, Xiuqing Wang, Jie Jin Auer, Paul L. Attia, John R. Yanek, Lisa R. Ahluwalia, Tarunveer S. Lahti, Jari Venturini, Cristina Tanaka, Toshiko Bielak, Lawrence F. Joshi, Peter K. Rocanin-Arjo, Ares Kolcic, Ivana Navarro, Pau Rose, Lynda M. Oldmeadow, Christopher Riess, Helene Mazur, Johanna Basu, Saonli Goel, Anuj Yang, Qiong Ghanbari, Mohsen Willemsen, Gonneke Rumley, Ann Fiorillo, Edoardo de Craen, Anton J. M. Grotevendt, Anne Scott, Robert Taylor, Kent D. Delgado, Graciela E. Yao, Jie Kifley, Annette Kooperberg, Charles Qayyum, Rehan Lopez, Lorna M. Berentzen, Tina L. Raikkonen, Katri Mangino, Massimo Bandinelli, Stefania Peyser, Patricia A. Wild, Sarah Tregouet, David-Alexandre Wright, Alan F. Marten, Jonathan Zemunik, Tatijana Morrison, Alanna C. Sennblad, Bengt Tofler, Geoffrey de Maat, Moniek P. M. de Geus, Eco J. C. Lowe, Gordon D. Zoledziewska, Magdalena Sattar, Naveed Binder, Harald Voelker, Uwe Waldenberger, Melanie Khaw, Kay-Tee Mcknight, Barbara Huang, Jie Jenny, Nancy S. Holliday, Elizabeth G. Qi, Lihong Mcevoy, Mark G. Becker, Diane M. Starr, John M. Sarin, Antti-Pekka Hysi, Pirro G. Hernandez, Dena G. Jhun, Min A. Campbell, Harry Hamsten, Anders Rivadeneira, Fernando Mcardle, Wendy L. Slagboom, P. Eline Zeller, Tanja Koenig, Wolfgang Psaty, Bruce M. Haritunians, Talin Liu, Jingmin Palotie, Aarno Uitterlinden, Andre G. Stott, David J. Hofman, Albert Franco, Oscar H. Polasek, Ozren Rudan, Igor Morange, Pierre-Emmanuel Wilson, James F. Kardia, Sharon L. R. Ferrucci, Luigi Spector, Tim D. Eriksson, Johan G. Hansen, Torben Deary, Ian J. Becker, Lewis C. Scott, Rodney J. Mitchell, Paul Maerz, Winfried Wareham, Nick J. Peters, Annette Greinacher, Andreas Wild, Philipp S. Jukema, J. Wouter Boomsma, Dorret I. Hayward, Caroline Cucca, Francesco Tracy, Russell Watkins, Hugh Reiner, Alex P. Folsom, Aaron R. Ridker, Paul M. O'Donnell, Christopher J. Smith, Nicholas L. Strachan, David P. Dehghan, Abbas TI A meta-analysis of 120 246 individuals identifies 18 new loci for fibrinogen concentration SO HUMAN MOLECULAR GENETICS LA English DT Article ID GENOME-WIDE ASSOCIATION; C-REACTIVE PROTEIN; CARDIOVASCULAR-DISEASE; CIRCULATING FIBRINOGEN; GENETIC ARCHITECTURE; VARIANTS; DESIGN; HEMOSTASIS; RESOURCE; HEALTH AB Genome-wide association studies have previously identified 23 genetic loci associated with circulating fibrinogen concentration. These studies used HapMap imputation and did not examine the X-chromosome. 1000 Genomes imputation provides better coverage of uncommon variants, and includes indels. We conducted a genome-wide association analysis of 34 studies imputed to the 1000 Genomes Project reference panel and including similar to 120 000 participants of European ancestry (95 806 participants with data on the X-chromosome). Approximately 10.7 million single-nucleotide polymorphisms and 1.2 million indels were examined. We identified 41 genome-wide significant fibrinogen loci; of which, 18 were newly identified. There were no genome-wide significant signals on the X-chromosome. The lead variants of five significant loci were indels. We further identified six additional independent signals, including three rare variants, at two previously characterized loci: FGB and IRF1. Together the 41 loci explain 3% of the variance in plasma fibrinogen concentration. C1 [de Vries, Paul S.; Ghanbari, Mohsen; Rivadeneira, Fernando; Uitterlinden, Andre G.; Hofman, Albert; Franco, Oscar H.; Dehghan, Abbas] Erasmus MC, Dept Epidemiol, Wytemaweg 80, Rotterdam, Netherlands. [de Maat, Moniek P. M.] Erasmus MC, Dept Hematol, Wytemaweg 80, Rotterdam, Netherlands. [Rivadeneira, Fernando; Uitterlinden, Andre G.] Erasmus MC, Dept Internal Med, Wytemaweg 80, Rotterdam, Netherlands. [Chasman, Daniel I.; Rose, Lynda M.; Ridker, Paul M.] Brigham & Womens Hosp, Div Prevent Med, 75 Francis St, Boston, MA 02115 USA. [Chasman, Daniel I.; Ridker, Paul M.] Harvard Univ, Sch Med, Boston, MA 02115 USA. [Sabater-Lleal, Maria; Sennblad, Bengt; Hamsten, Anders] Karolinska Inst, Atherosclerosis Res Unit, Cardiovasc Genet & Genom Grp, Dept Med, Stockholm, Sweden. [Sennblad, Bengt] Karolinska Inst, Sci Life Lab, Stockholm, Sweden. [Chen, Ming-Huei] Boston Univ, Sch Med, Dept Neurol, Boston, MA 02215 USA. [Chen, Ming-Huei; Huffman, Jennifer E.; Yang, Qiong; O'Donnell, Christopher J.] NHLBI, Framingham Heart Study, Populat Sci Branch, Div Intramural Res,NIH, Framingham, MA USA. [Huffman, Jennifer E.; Navarro, Pau; Wright, Alan F.; Marten, Jonathan; Wilson, James F.; Hayward, Caroline] Univ Edinburgh, Inst Genet & Mol Med, MRC, Human Genet Unit, Edinburgh, Midlothian, Scotland. [Marioni, Riccardo E.; Lopez, Lorna M.; Starr, John M.; Deary, Ian J.] Univ Edinburgh, Ctr Cognit Ageing & Cognit Epidemiol, Edinburgh, Midlothian, Scotland. [Marioni, Riccardo E.] Univ Edinburgh, Ctr Genom & Expt Med, Edinburgh, Midlothian, Scotland. [Joshi, Peter K.; Wild, Sarah] Univ Edinburgh, Usher Inst Populat Hlth Sci & Informat, Ctr Populat Hlth Sci, Edinburgh, Midlothian, Scotland. [Joshi, Peter K.; Campbell, Harry; Polasek, Ozren; Rudan, Igor; Wilson, James F.] Univ Edinburgh, Usher Inst Populat Hlth Sci & Informat, Ctr Global Hlth Res, Edinburgh, Midlothian, Scotland. [Starr, John M.] Univ Edinburgh, Alzheimer Scotland Dementia Res Ctr, Edinburgh, Midlothian, Scotland. [Deary, Ian J.] Univ Edinburgh, Dept Psychol, Edinburgh, Midlothian, Scotland. [Steri, Maristella; Fiorillo, Edoardo; Zoledziewska, Magdalena; Cucca, Francesco] CNR, Ist Ric Genet & Biomed, Cagliari, Italy. [Tang, Weihong; Folsom, Aaron R.] Univ Minnesota, Div Epidemiol & Community Hlth, Minneapolis, MN USA. [Basu, Saonli] Univ Minnesota, Div Biostat, Minneapolis, MN USA. [Teumer, Alexander] Univ Med Greifswald, Inst Community Med, Greifswald, Germany. [Grotevendt, Anne] Univ Med Greifswald, Inst Clin Chem & Lab Med, Greifswald, Germany. [Voelker, Uwe] Univ Med Greifswald, Interfac Inst Genet & Funct Genom, Greifswald, Germany. [Greinacher, Andreas] Univ Med Greifswald, Inst Immunol & Transfus Med, Greifswald, Germany. [Marioni, Riccardo E.] Univ Queensland, Queensland Brain Inst, Brisbane, Qld, Australia. [Grossmann, Vera; Wild, Philipp S.] Johannes Gutenberg Univ Mainz, Univ Med Ctr, Ctr Thrombosis & Hemostasis, D-55122 Mainz, Germany. [Mazur, Johanna; Binder, Harald] Johannes Gutenberg Univ Mainz, Univ Med Ctr, Inst Med Biostat Epidemiol & Informat, D-55122 Mainz, Germany. [Wild, Philipp S.] Johannes Gutenberg Univ Mainz, Univ Med Ctr, Dept Med 2, Prevent Cardiol & Prevent Med, D-55122 Mainz, Germany. [Hottenga, Jouke J.; Willemsen, Gonneke; de Geus, Eco J. C.; Boomsma, Dorret I.] Vrije Univ Amsterdam, Netherlands Twin Register, Dept Biol Psychol, Amsterdam, Netherlands. [Trompet, Stella; Jukema, J. Wouter] Leiden Univ, Med Ctr, Dept Cardiol, Leiden, Netherlands. [Trompet, Stella; de Craen, Anton J. M.] Leiden Univ, Med Ctr, Dept Gerontol & Geriatr, Leiden, Netherlands. [Slagboom, P. Eline] Leiden Univ, Med Ctr, Dept Mol Epidemiol, Leiden, Netherlands. [Mueller-Nurasyid, Martina] German Res Ctr Environm Hlth, Helmholtz Zentrum Munchen, Inst Genet Epidemiol, Neuherberg, Germany. [Riess, Helene; Waldenberger, Melanie; Peters, Annette] German Res Ctr Environm Hlth, Helmholtz Zentrum Munchen, Inst Epidemiol 2, Neuherberg, Germany. [Waldenberger, Melanie] German Res Ctr Environm Hlth, Helmholtz Zentrum Munchen, Res Unit Mol Epidemiol, Neuherberg, Germany. [Mueller-Nurasyid, Martina] Univ Munich, Dept Med 1, Munich, Germany. [Mueller-Nurasyid, Martina; Koenig, Wolfgang; Peters, Annette] Partner Site Munich Heart Alliance, DZHK German Ctr Cardiovasc Res, Munich, Germany. [Zhao, Jing Hua; Scott, Robert; Wareham, Nick J.] Univ Cambridge, Sch Clin Med, MRC, Epidemiol Unit, Cambridge, England. [Khaw, Kay-Tee] Univ Cambridge, Sch Clin Med, Clin Gerontol Unit, Cambridge, England. [Brody, Jennifer A.] Univ Washington, Dept Med, Seattle, WA 98195 USA. [Mcknight, Barbara] Univ Washington, Dept Biostat, Seattle, WA 98195 USA. [Psaty, Bruce M.] Univ Washington, Dept Med Epidemiol & Hlth Serv, Seattle, WA 98195 USA. [Smith, Nicholas L.] Univ Washington, Dept Epidemiol, Seattle, WA 98195 USA. [Kleber, Marcus E.; Delgado, Graciela E.; Maerz, Winfried] Heidelberg Univ, Med Fac Mannheim, Dept Med 5, Mannheim, Germany. [Guo, Xiuqing; Taylor, Kent D.; Yao, Jie] Univ Calif Los Angeles, Med Ctr, Inst Translat Genom & Populat Sci, Torrance, CA 90509 USA. [Guo, Xiuqing] Univ Calif Los Angeles, Med Ctr, Los Angeles Biomed Res Inst Harbor, Dept Pediat, Torrance, CA 90509 USA. [Wang, Jie Jin; Kifley, Annette; Mitchell, Paul] Univ Sydney, Westmead Millennium Inst Med Res, Ctr Vis Res, Dept Ophthalmol, Sydney, NSW 2006, Australia. [Auer, Paul L.] Univ Wisconsin, Zilber Sch Publ Hlth, Milwaukee, WI 53201 USA. [Attia, John R.; Oldmeadow, Christopher] Hunter Med Res Inst, Publ Hlth Stream, New Lambton Hts, Australia. [Scott, Rodney J.] Hunter Med Res Inst, Informat Based Med Program, New Lambton Hts, Australia. [Attia, John R.; Oldmeadow, Christopher] Univ Newcastle, Sch Med & Publ Hlth, New Lambton Hts, Australia. [Scott, Rodney J.] Univ Newcastle, Sch Biomed Sci & Pharm, New Lambton Hts, Australia. [Yanek, Lisa R.; Qayyum, Rehan; Becker, Diane M.; Becker, Lewis C.] Johns Hopkins Univ, Sch Med, Dept Med, Baltimore, MD 21205 USA. [Ahluwalia, Tarunveer S.; Hansen, Torben] Univ Copenhagen, Fac Hlth & Med Sci, Sect Metab Genet, Novo Nordisk Fdn,Ctr Basic Metab Res, Copenhagen, Denmark. [Ahluwalia, Tarunveer S.] Univ Copenhagen, Fac Hlth & Med Sci, Copenhagen Prospect Studies Asthma Childhood, Copenhagen, Denmark. [Ahluwalia, Tarunveer S.] Gentofte Univ Hosp, Danish Pediat Asthma Ctr, Copenhagen, Denmark. [Lahti, Jari; Raikkonen, Katri] Univ Helsinki, Inst Behav Sci, Helsinki, Finland. [Sarin, Antti-Pekka; Palotie, Aarno] Univ Helsinki, Inst Mol Med Finland FIMM, Helsinki, Finland. [Eriksson, Johan G.] Univ Helsinki, Dept Gen Practice & Primary Hlth Care, Helsinki, Finland. [Lahti, Jari; Eriksson, Johan G.] Folkhalsan Res Ctr, Helsinki, Finland. [Venturini, Cristina] UCL, Inst Opthalmol, London, England. [Venturini, Cristina; Mangino, Massimo; Hysi, Pirro G.; Spector, Tim D.] Kings Coll London, Dept Twin Res & Genet Epidemiol, London WC2R 2LS, England. [Tanaka, Toshiko; Ferrucci, Luigi] NIA, Translat Gerontol Branch, Baltimore, MD 21224 USA. [Bielak, Lawrence F.; Peyser, Patricia A.; Jhun, Min A.; Kardia, Sharon L. R.] Univ Michigan, Dept Epidemiol, Ann Arbor, MI 48109 USA. [Rocanin-Arjo, Ares; Tregouet, David-Alexandre] INSERM, Unite Mixte Rech Sante UMR S 1166, F-75013 Paris, France. [Rocanin-Arjo, Ares; Tregouet, David-Alexandre] Univ Paris 06, Sorbonne Univ, UMR S 1166, Team Genom & Pathophysiol Cardiovasc Dis, F-75013 Paris, France. [Rocanin-Arjo, Ares; Tregouet, David-Alexandre] Inst Cardiometab & Nutr ICAN, F-75013 Paris, France. [Kolcic, Ivana] Univ Split, Fac Med, Dept Publ Hlth, Split, Croatia. [Zemunik, Tatijana] Univ Split, Sch Med, Dept Biol, Split, Croatia. [Polasek, Ozren] Univ Split, Ctr Global Hlth, Fac Med, Dept Publ Hlth, Split, Croatia. [Goel, Anuj; Watkins, Hugh] Univ Oxford, Wellcome Trust Ctr Human Genet, Radcliffe Dept Med, Dept Cardiovasc Med, Oxford, England. [Yang, Qiong] Boston Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02215 USA. [Ghanbari, Mohsen] Mashhad Univ Med Sci, Sch Med, Dept Genet, Mashhad, Iran. [Rumley, Ann; Lowe, Gordon D.; Stott, David J.; Smith, Nicholas L.] Univ Glasgow, Fac Med, Inst Cardiovasc & Med Sci, Glasgow, Lanark, Scotland. [Kooperberg, Charles; Liu, Jingmin; Reiner, Alex P.] Fred Hutchinson Canc Res Ctr, 1124 Columbia St, Seattle, WA 98104 USA. [Lopez, Lorna M.] Beaumont Hosp, Educ & Res Ctr, Royal Coll Surg Ireland, Dept Psychiat, Dublin 9, Ireland. [Lopez, Lorna M.] Univ Coll Dublin, Ctr Proteome Res, Conway Inst, Dublin 2, Ireland. [Berentzen, Tina L.] Bispebjerg & Frederiksberg Hosp, Inst Prevent Med, Copenhagen, Denmark. [Bandinelli, Stefania] ASF, Geriatr Unit, Florence, Italy. [Morrison, Alanna C.] Univ Texas Houston, Hlth Sci Ctr, Ctr Human Genet, Houston, TX USA. [Tofler, Geoffrey] Univ Sydney, Royal N Shore Hosp, Sydney, NSW 2006, Australia. [de Geus, Eco J. C.] Vrije Univ Amsterdam, EMGO Inst, Amsterdam, Netherlands. [de Geus, Eco J. C.] Vrije Univ Amsterdam Med Ctr, Amsterdam, Netherlands. [Sattar, Naveed] BHF Glasgow Cardiovasc Res Ctr, Fac Med, Glasgow, Lanark, Scotland. [Huang, Jie] Wellcome Trust Sanger Inst, Dept Human Genet, Cambridge, England. [Jenny, Nancy S.; Tracy, Russell] Univ Vermont, Coll Med, Ctr Clin & Translat Sci, Dept Pathol & Lab Med, Colchester, VT USA. [Holliday, Elizabeth G.] Univ Newcastle, Sch Med & Publ Hlth, Hunter Med Res Inst, Publ Hlth Stream, Newcastle, NSW 2300, Australia. [Mcevoy, Mark G.] Univ Newcastle, Sch Med & Publ Hlth, Newcastle, NSW 2300, Australia. [Qi, Lihong] Univ Calif Davis, Dept Publ Hlth Sci, Div Biostat, Davis, CA USA. [Sarin, Antti-Pekka] Natl Inst Hlth & Welf, Publ Hlth Genom Unit, Helsinki, Finland. [Hernandez, Dena G.] NIA, Neurogenet Lab, Bethesda, MD 20892 USA. [Mcardle, Wendy L.] Univ Bristol, Sch Social & Community Med, Bristol, Avon, England. [Zeller, Tanja] Univ Med Ctr Hamburg Eppendorf, Univ Heart Ctr, Dept Gen & Intervent Cardiol, Hamburg, Germany. [Zeller, Tanja] German Ctr Cardiovasc Res DZHK, Partner Site Hamburg, Hamburg, Germany. [Koenig, Wolfgang] Univ Ulm, Med Ctr, Dept Internal Med Cardiol 2, D-89069 Ulm, Germany. [Koenig, Wolfgang] Tech Univ Munich, Deutsch Herzzentrum Munchen, D-80290 Munich, Germany. [Psaty, Bruce M.] Grp Hlth Cooperat Puget Sound, Grp Hlth Res Inst, Seattle, WA USA. [Haritunians, Talin] Cedars Sinai Med Ctr, Inflammatory Bowel & Immunobiol Res Inst, Los Angeles, CA 90048 USA. [Morange, Pierre-Emmanuel] La Timone Hosp, Haematol Lab, F-13385 Marseille, France. [Morange, Pierre-Emmanuel] INSERM, UMR S 1062, Nutr Obes & Risk Thrombosis, F-13385 Marseille, France. [Morange, Pierre-Emmanuel] Aix Marseille Univ, UMR S 1062, Nutr Obes & Risk Thrombosis, F-13385 Marseille, France. [Eriksson, Johan G.] Natl Inst Hlth & Welfare, Helsinki, Finland. [Eriksson, Johan G.] Univ Helsinki, Cent Hosp, Unit Gen Practice, Helsinki, Finland. [Maerz, Winfried] Synlab Serv LLC, Synlab Acad, Mannheim, Germany. [Maerz, Winfried] Med Univ Graz, Chem Lab Diagnost, Inst Clin Med, Graz, Austria. [Wild, Philipp S.] German Ctr Cardiovasc Res DZHK, Partner Site RheinMain, Mainz, Germany. [Jukema, J. Wouter] Durrer Ctr Cardiogenet Res, Amsterdam, Netherlands. [Jukema, J. Wouter] Interuniv Cardiol Inst Netherlands, Utrecht, Netherlands. [Reiner, Alex P.] Univ Washington, Seattle, WA 98195 USA. [O'Donnell, Christopher J.] Massachusetts Gen Hosp, NHLBI, Div Intramural Res, Boston, MA 02114 USA. [O'Donnell, Christopher J.] Massachusetts Gen Hosp, Div Cardiol, Boston, MA 02114 USA. [Smith, Nicholas L.] Seattle Epidemiol Res & Informat Ctr, Off Res & Dev, Dept Vet Affairs, Seattle, WA USA. [Strachan, David P.] St Georges Univ London, Populat Hlth Res Inst, London, England. RP Dehghan, A (reprint author), Erasmus MC, Dept Epidemiol, Wytemaweg 80, Rotterdam, Netherlands. EM a.dehghan@erasmusmc.nl RI Waldenberger, Melanie/B-5355-2014; Kolcic, Ivana/E-2713-2017; Tregouet, David-Alexandre/E-3961-2016; mangino, massimo/F-5134-2011; Peters, Annette/A-6117-2011; Slagboom, P. Eline/R-4790-2016; Polasek, Ozren/B-6002-2011 OI Lahti, Jari/0000-0002-4310-5297; Raikkonen, Katri/0000-0003-3124-3470; de Geus, Eco/0000-0001-6022-2666; Dehghan, Abbas/0000-0001-6403-016X; Sabater Lleal, Maria/0000-0002-0128-379X; Peters, Annette/0000-0001-6645-0985; Waldenberger, Melanie/0000-0003-0583-5093; Kolcic, Ivana/0000-0001-7918-6052; Kleber, Marcus/0000-0003-0663-7275; mangino, massimo/0000-0002-2167-7470; Watkins, Hugh/0000-0002-5287-9016; Slagboom, P. Eline/0000-0002-2875-4723; Polasek, Ozren/0000-0002-5765-1862 FU National Heart, Lung and Blood Institute [R01HL105756, HL087660, HL100245, HL043851, HL080467]; National Heart, Lung and Blood Institute (NHLBI) [R01HL105756, R01HL087641, R01HL59367, R01HL086694, HHSN268201200036C, HHSN268200800007C, N01HC55222, N01HC85079, N01HC85080, N01HC85081, N01HC85082, N01HC85083, N01HC85086, U01HL080295, R01HL087652, R01HL103612, R01HL120393, N01-HC-65226]; National Human Genome Research Institute [U01HG004402]; National Institutes of Health [HHSN268200625226C]; National Institutes of Health and NIH Roadmap for Medical Research [UL1RR025005]; Medical Research Council [G0000934]; Wellcome Trust [068545/Z/02, 076113/B/04/Z, 075491/Z/04]; National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK); National Institute of Allergy and Infectious Diseases (NIAID); National Human Genome Research Institute (NHGRI); National Institute of Child Health and Human Development (NICHD); Juvenile Diabetes Research Foundation International (JDRF); Juvenile Diabetes Research Foundation International; National Institute for Health Research Cambridge Biomedical Research Centre; European Commission Framework Programme 6 [018996]; French Ministry of Research; Australian National Health AMP; Medical Research Council, Canberra Australia [974159, 211069, 457349, 512423, 475604, 529912, 529923]; Wellcome Trust, UK; National Institute of Neurological Disorders and Stroke (NINDS); National Institute on Aging (NIA) [R01AG023629]; National Center for Advancing Translational Sciences; CTSI grant [UL1TR000124]; National Institute of Diabetes and Digestive and Kidney Disease Diabetes Research Center [DK063491]; Medical Research Council (UK); European Commission Framework 6 project EUROSPAN [LSHG-CT-2006-018947]; Republic of Croatia Ministry of Science, Education and Sports [108-1080315-0302]; Cancer Research UK; European Union; Stroke Association; British Heart Foundation; Department of Health; Food Standards Agency; National Heart, Lung, and Blood Institute's (NHLBI'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 and Boston Medical Center; National Institute of Diabetes and Digestive and Kidney Diseases [K24 DK080140]; National Institute on Aging and National Institute for Neurological Disorders and Stroke [R01 AG033193, NS017950]; National Institutes of Health/National Heart, Lung and Blood Institute [U01 HL72518, HL097698, HL59684, HL071025-01A1]; National Institutes of Health/National Institute of Nursing Research [NR0224103]; National Institutes of Health/National Center for Research Resources [M01-RR000052]; GENDINOB project; government of Rhineland-Palatinate ('Stiftung Rheinland-Pfalz fur Innovation') [AZ 961-386261/733]; research program 'Wissen schafft Zukunft' of Johannes Gutenberg-University of Mainz; research program 'Center for Translational Vascular Biology (CTVB)' of the Johannes Gutenberg-University of Mainz; Boehringer Ingelheim; PHILIPS Medical Systems; Federal Ministry of Education and Research [BMBF 01EO1003, 01ZZ9603, 01ZZ0103, 01ZZ0403, 03ZIK012]; 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; Italian Ministry of Health [ICS110.1/RF97.71]; US National Institute on Aging [263 MD 9164, 263 MD 821336]; Intramural Research Program of the NIH, National Institute on Aging; Helmholtz Zentrum Munchen; German Research Center for Environmental Health, Neuherberg, Germany; German Federal Ministry of Education and Research (BMBF); state of Bavaria; German National Genome Research Network (NGFNPlus) [01GS0834]; University of Ulm; Munich Center of Health Sciences (MC Health) as part of LMU innovative; Biotechnology and Biological Sciences Research Council (BBSRC) [BB/F019394/1, LBC1921]; Age UK [LBC1936]; Engineering and Physical Sciences Research Council (EPSRC); Economic and Social Research Council (ESRC); Medical Research Council (MRC); sixth Framework Program (integrated project Bloodomics) [LSHM-CT-2004-503485]; seventh Framework Program (Atheroremo) of the European Union [201668]; seventh Framework Program (RiskyCAD) of the European Union [305739]; INTERREG IV Oberrhein Program [A28]; European Regional Development Fund (ERDF); Wissenschaftsoffensive TMO; Program Hospitalier de Recherche Clinique; Region Ile de France; Pierre and Marie Curie University; ICAN Institute for Cardiometabolism and Nutrition [ANR-10-IAHU-05]; Netherlands Organization for Scientific Research (NWO); MagW/ZonMW [904-61-090, 985-10-002, 904-61-193, 480-04-004, 400-05-717, addiction-31160008, middelgroot-911-09-032, Spinozapremie 56-464-14192]; Center for Medical Systems Biology (CSMB, NWO Genomics); NBIC/BioAssist/RK [2008.024]; Biobanking and Biomolecular Resources Research Infrastructure (BBMRI-NL) [184.021.007]; VU University's Institute for Health and Care Research (EMGO+); Neuroscience Campus Amsterdam (NCA); European Science Foundation (ESF) [EU/QLRT-2001-01254]; European Community's Seventh Framework Program, ENGAGE [HEALTH-F4-2007-201413]; European Science Council (ERC Advanced) [230374]; Rutgers University Cell and DNA Repository [NIMH U24 MH068457-06]; Avera Institute, Sioux Falls, South Dakota (USA); National Institutes of Health (NIH) [R01D0042157-01A, MH081802, 1RC2 MH089951]; Genetic Association Information Network (GAIN) of the Foundation for the National Institutes of Health; BiG Grid; Dutch e-Science Grid; NWO; Chief Scientist Office of the Scottish Government; Royal Society; MRC Human Genetics Unit; Arthritis Research UK; European Community Sixth Framework Program [LSHM-CT-2007-037273]; AstraZeneca; Swedish Research Council; Knut and Alice Wallenberg Foundation; Swedish Heart-Lung Foundation; Torsten and Ragnar Soderberg Foundation; Strategic Cardiovascular and Diabetes Programs of Karolinska Institutet; Stockholm County Council; Foundation for Strategic Research; BHF Centre of Research Excellence, Oxford; Swedish Heart-Lung Foundation [20130399]; Ake Wiberg and Tore Nilssons foundations; Magnus Bergvall Foundation; Foundation for Old Servants; European Union's Seventh Framework Programme [HEALTH-F2-2009-223004]; Netherlands Consortium of Healthy Aging [NGI: 05060810]; Scottish Executive Chief Scientist Office, Health Services Research Committee [CZG/4/306]; Research Institute for Diseases in the Elderly [014-93-015, RIDE2]; Netherlands Genomics Initiative (NGI)/Netherlands Organisation for Scientific Research (NWO) [050-060-810]; Erasmus Medical Center and Erasmus University, Rotterdam; Netherlands Organization for the Health Research and Development (ZonMw); 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; NWO grant (veni) [916.12.154]; EUR Fellowship; NIA [NO1-AG-1-2109]; Sardinian Autonomous Region [7/2009, cRP3-154]; FaReBio2011 'Farmaci e Reti Biotecnologiche di Qualita'; Ministry of Cultural Affairs; Social Ministry of the Federal State of Mecklenburg-West Pomerania; Siemens Healthcare, Erlangen, Germany; Federal State of Mecklenburg West Pomerania; Leibniz Supercomputing Centre of the Bavarian Academy of Sciences and Humanities (HLRB project) [h1231]; Ministry of Cultural Affairs of the Federal State of Mecklenburg-West Pomerania [03IS2061A]; National Institute for Health Research (NIHR) Clinical Research Facility at Guy's AMP; St Thomas' NHS Foundation Trust; NIHR Biomedical Research Centre based at Guy's and St Thomas' NHS Foundation Trust; Wellcome Trust Sanger Institute and National Eye Institute via NIH/CIDR; National Cancer Institute [CA047988]; Donald W. Reynolds Foundation; Fondation Leducq; Amgen; National Heart, Lung and Blood Institute, National Institutes of Health, US Department of Health and Human Services [HHSN268201100046C, HHSN268201100001C, HHSN268201100002C, HHSN268201100003C, HHSN268201100004C, HHSN271201100004C]; Women's Health Initiative Sequencing Project [NHLBI RC2 HL102924]; Genetics and Epidemiology of Colorectal Cancer Consortium [NCI CA137088]; Genomics and Randomized Trials Network [NHGRI U01-HG005152]; NCI training grant [R25CA094880]; King's College London FX Infrastructure for the CHARGE Consortium is supported in part by the National Heart, Lung and Blood Institute grant R01HL105756. ARIC is carried out as a collaborative study supported by National Heart, Lung and Blood Institute (NHLBI) contracts HHSN268201100005C, HHSN268201100006C, HHSN268201100007C, HHSN268201100008C, HHSN268201100009C, HHSN268201100010C, HHSN268201100011C and HHSN268201100012C, R01HL087641, R01HL59367 and R01HL086694; National Human Genome Research Institute contract U01HG004402 and National Institutes of Health contract HHSN268200625226C. Infrastructure was partly supported by grant number UL1RR025005, a component of the National Institutes of Health and NIH Roadmap for Medical Research. B58C acknowledges use of phenotype and genotype data from the British 1958 Birth Cohort DNA collection, funded by the Medical Research Council grant G0000934 and the Wellcome Trust grant 068545/Z/02. Genotyping for the B58C-WTCCC subset was funded by the Wellcome Trust grant 076113/B/04/Z. The B58C-T1DGC genotyping utilized resources provided by the Type 1 Diabetes Genetics Consortium, a collaborative clinical study sponsored by the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK), National Institute of Allergy and Infectious Diseases (NIAID), National Human Genome Research Institute (NHGRI), National Institute of Child Health and Human Development (NICHD), and Juvenile Diabetes Research Foundation International (JDRF) and supported by U01 DK062418. B58C-T1DGC GWAS data were deposited by the Diabetes and Inflammation Laboratory, Cambridge Institute for Medical Research (CIMR), University of Cambridge, which is funded by Juvenile Diabetes Research Foundation International, the Wellcome Trust and the National Institute for Health Research Cambridge Biomedical Research Centre; the CIMR is in receipt of a Wellcome Trust Strategic Award (079895). The B58C-GABRIEL genotyping was supported by a contract from the European Commission Framework Programme 6 (018996) and grants from the French Ministry of Research. BMES has been supported by the Australian National Health & Medical Research Council, Canberra Australia (grant numbers 974159, 211069, 457349, 512423, 475604, 529912 and the funding for Centre for Clinical Research Excellence in Translational Clinical Research in Eye Diseases, CCRE in TCR-Eye, grant ID 529923); in addition, funding by the Wellcome Trust, UK (to A. Viswanathan, P. McGuffin, P. Mitchell, F. Topouzis and P. Foster) has supported the genotyping costs of the entire BMES population. This CHS research was supported by NHLBI contracts HHSN268201200036C, HHSN268200800007C, N01HC55222, N01HC85079, N01HC85080, N01HC85081, N01HC85082, N01HC85083, N01HC85086 and NHLBI grants U01HL080295, R01HL087652, R01HL105756, R01HL103612 and R01HL120393 with additional contribution from the National Institute of Neurological Disorders and Stroke (NINDS). Additional support was provided through R01AG023629 from the National Institute on Aging (NIA). The provision of genotyping data was supported in part by the National Center for Advancing Translational Sciences, CTSI grant UL1TR000124 and the National Institute of Diabetes and Digestive and Kidney Disease Diabetes Research Center (DRC) grant DK063491 to the Southern California Diabetes Endocrinology Research Center. The CROATIA-Split study was funded by grants from the Medical Research Council (UK), European Commission Framework 6 project EUROSPAN (contract no.; r LSHG-CT-2006-018947) and Republic of Croatia Ministry of Science, Education and Sports research grants to I.R. (108-1080315-0302). The CROATIA-Korcula study was funded by grants from the Medical Research Council (UK), 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 I.R. (108-1080315-0302). The CROATIA-Vis study was funded by grants from the Medical Research Council (UK) and Republic of Croatia Ministry of Science, Education and Sports research grants to I.R. (108-1080315-0302). The EPIC Norfolk Study is funded by program grants from the Medical Research Council UK and Cancer Research UK, and by additional support from the European Union, Stroke Association, British Heart Foundation, Department of Health, Food Standards Agency, and the Wellcome Trust. FHS was partially supported by the National Heart, Lung, and Blood Institute's (NHLBI'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. Partial investigator support was provided by the National Institute of Diabetes and Digestive and Kidney Diseases K24 DK080140 (J.B. Meigs), the National Institute on Aging and National Institute for Neurological Disorders and Stroke R01 AG033193, NS017950 (S Seshadri). GeneSTAR was supported by grants from the National Institutes of Health/National Heart, Lung and Blood Institute (U01 HL72518, HL097698, HL59684 and HL071025-01A1), the National Institutes of Health/National Institute of Nursing Research (NR0224103) and the National Institutes of Health/National Center for Research Resources (M01-RR000052) to the Johns Hopkins General Clinical Research Center. The Genetic Epidemiology Network of Arteriopathy (GENOA) study is supported by the National Institutes of Health, grant numbers HL087660 and HL100245 from National Heart, Lung, Blood Institute. Tarunveer Singh Ahluwalia received his post-doctoral research funding from GENDINOB project and acknowledges the same. The Gutenberg Health Study is funded through the government of Rhineland-Palatinate ('Stiftung Rheinland-Pfalz fur Innovation', contract AZ 961-386261/733), the research programs 'Wissen schafft Zukunft' and 'Center for Translational Vascular Biology (CTVB)' of the Johannes Gutenberg-University of Mainz, and its contract with Boehringer Ingelheim and PHILIPS Medical Systems, including an unrestricted grant for the Gutenberg Health Study. V.G. and P.S.W. are funded by the Federal Ministry of Education and Research (BMBF 01EO1003). 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. The InCHIANTI study baseline (1998-2000) was supported as a 'targeted project' (ICS110.1/RF97.71) by the Italian Ministry of Health and in part by the US National Institute on Aging (contracts: 263 MD 9164 and 263 MD 821336); this research was supported in part by the Intramural Research Program of the NIH, National Institute on Aging.; r The KORA studies were financed by the Helmholtz Zentrum Munchen, German Research Center for Environmental Health, Neuherberg, Germany, and supported by grants from the German Federal Ministry of Education and Research (BMBF) and by the state of Bavaria. Part of this work was financed by the German National Genome Research Network (NGFNPlus, project number 01GS0834) and through additional funds from the University of Ulm. Furthermore, the research was supported within the Munich Center of Health Sciences (MC Health) as part of LMU innovative. The whole genome association study was funded by the Biotechnology and Biological Sciences Research Council (BBSRC; Ref. BB/F019394/1). The LBC1936 research was supported by Age UK. The LBC1921 data collection was funded by the BBSRC. 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 (BBSRC), Engineering and Physical Sciences Research Council (EPSRC), Economic and Social Research Council (ESRC) and Medical Research Council (MRC) is gratefully acknowledged. LURIC has received funding from the sixth Framework Program (integrated project Bloodomics, grant no.: LSHM-CT-2004-503485) and from the seventh Framework Program (Atheroremo, grant agreement number 201668 and RiskyCAD, grant agreement number 305739) of the European Union as well as from the INTERREG IV Oberrhein Program (Project A28, Genetic mechanisms of cardiovascular diseases) with support from the European Regional Development Fund (ERDF) and the Wissenschaftsoffensive TMO. The MARTHA project was supported by grants from the Program Hospitalier de Recherche Clinique. Statistical analyses of the MARTHA dataset were performed using the C2BIG computing cluster, funded by the Region Ile de France, Pierre and Marie Curie University, and the ICAN Institute for Cardiometabolism and Nutrition (ANR-10-IAHU-05). MESA and the MESA SHARe project are conducted and supported by the National Heart, Lung and Blood Institute (NHLBI) in collaboration with MESA investigators. Support is provided by grants and contracts N01 HC-95159, N01-HC-95160, N01-HC-95161, N01-HC-95162, N01-HC-95163, N01-HC-95164, N01-HC-95165, N01-HC-95166, N01-HC-95167, N01-HC-95168, N01-HC-95169 and RR-024156. Funding for CARe genotyping was provided by NHLBI Contract N01-HC-65226. The provision of genotyping data was supported in part by the National Center for Advancing Translational Sciences, CTSI grant UL1TR000124, and the National Institute of Diabetes and Digestive and Kidney Disease Diabetes Research Center (DRC) grant DK063491 to the Southern California Diabetes Endocrinology Research Center. NTR: funding was obtained from the Netherlands Organization for Scientific Research (NWO) and MagW/ZonMW grants 904-61-090, 985-10-002, 904-61-193,480-04-004, 400-05-717, addiction-31160008, middelgroot-911-09-032, Spinozapremie 56-464-14192, Center for Medical Systems Biology (CSMB, NWO Genomics), NBIC/BioAssist/RK(2008.024), Biobanking and Biomolecular Resources Research Infrastructure (BBMRI-NL, 184.021.007).; r VU University's Institute for Health and Care Research (EMGO+) and Neuroscience Campus Amsterdam (NCA); the European Science Foundation (ESF, EU/QLRT-2001-01254), the European Community's Seventh Framework Program (FP7/2007-2013), ENGAGE (HEALTH-F4-2007-201413); the European Science Council (ERC Advanced, 230374), Rutgers University Cell and DNA Repository (NIMH U24 MH068457-06), the Avera Institute, Sioux Falls, South Dakota (USA) and the National Institutes of Health (NIH, R01D0042157-01A, MH081802, Grand Opportunity grants 1RC2 MH089951). Part of the genotyping and analyses were funded by the Genetic Association Information Network (GAIN) of the Foundation for the National Institutes of Health. Computing was supported by BiG Grid, the Dutch e-Science Grid, which is financially supported by NWO. ORCADES was supported by the Chief Scientist Office of the Scottish Government, the Royal Society, the MRC Human Genetics Unit, Arthritis Research UK 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. PROCARDIS was supported by the European Community Sixth Framework Program (LSHM-CT-2007-037273), AstraZeneca, the British Heart Foundation, the Wellcome Trust (contract no. 075491/Z/04), the Swedish Research Council, the Knut and Alice Wallenberg Foundation, the Swedish Heart-Lung Foundation, the Torsten and Ragnar Soderberg Foundation, the Strategic Cardiovascular and Diabetes Programs of Karolinska Institutet and Stockholm County Council, the Foundation for Strategic Research and the Stockholm County Council. Jemma C. Hopewell and Robert Clarke acknowledge support from the BHF Centre of Research Excellence, Oxford. M. Sabater-Lleal is supported by the Swedish Heart-Lung Foundation (20130399), and acknowledges funding from Ake Wiberg and Tore Nilssons foundations. B. Sennblad acknowledges funding from the Magnus Bergvall Foundation and the Foundation for Old Servants. PROSPER-PHASE received funding from the European Union's Seventh Framework Programme (FP7/2007-2013) under grant agreement no. HEALTH-F2-2009-223004. For a part of the genotyping we received funding from the Netherlands Consortium of Healthy Aging (NGI: 05060810). Measurement of serum fibrinogen was supported by a grant from the Scottish Executive Chief Scientist Office, Health Services Research Committee grant number CZG/4/306. This work was performed as part of an ongoing collaboration of the PROSPER study group in the universities of Leiden, Glasgow and Cork. Professor Dr J.W.J. is an Established Clinical Investigator of the Netherlands Heart Foundation (2001 D 032). The generation and management of GWAS genotype data for the Rotterdam Study is supported by the Netherlands Organisation of Scientific Research NWO Investments (no. 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 (NGI)/Netherlands Organisation for Scientific Research (NWO) project no. 050-060-810. The Rotterdam Study is funded by Erasmus Medical Center and Erasmus University, Rotterdam, Netherlands Organization for the Health Research and Development (ZonMw), 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), and the Municipality of Rotterdam. A. D. is supported by NWO grant (veni, 916.12.154) and the EUR Fellowship.; r The SardiNIA ('ProgeNIA') team was supported by contract NO1-AG-1-2109 from the NIA. This research was supported by the Intramural Research Program of the NIH, National Institute on Aging, by Sardinian Autonomous Region (L.R. no. 7/2009) grant cRP3-154, and by grant FaReBio2011 'Farmaci e Reti Biotecnologiche di Qualita'. SHIP is part of the Community Medicine Research net of the University of Greifswald, Germany, which is funded by the Federal Ministry of Education and Research (grants no. 01ZZ9603, 01ZZ0103 and 01ZZ0403), the Ministry of Cultural Affairs as well as the Social Ministry of the Federal State of Mecklenburg-West Pomerania. Genome-wide data have been supported by the Federal Ministry of Education and Research (grant no. 03ZIK012) and a joint grant from Siemens Healthcare, Erlangen, Germany and the Federal State of Mecklenburg West Pomerania. Computing resources have been made available by the Leibniz Supercomputing Centre of the Bavarian Academy of Sciences and Humanities (HLRB project h1231). The University of Greifswald is a member of the 'Center of Knowledge Interchange' program of the Siemens AG and the Cache Campus program of the InterSystems GmbH. This work is also part of the research project Greifswald Approach to Individualized Medicine (GANI_MED). The GANI_MED consortium is funded by the Federal Ministry of Education and Research and the Ministry of Cultural Affairs of the Federal State of Mecklenburg-West Pomerania (03IS2061A). TwinsUK was funded by the Wellcome Trust; European Community's Seventh Framework Programme (FP7/2007-2013). The study also receives support from the National Institute for Health Research (NIHR) Clinical Research Facility at Guy's & St Thomas' NHS Foundation Trust and NIHR Biomedical Research Centre based at Guy's and St Thomas' NHS Foundation Trust and King's College London. Tim Spector is an NIHR senior Investigator and is holder of an ERC Advanced Principal Investigator award. SNP Genotyping was performed by The Wellcome Trust Sanger Institute and National Eye Institute via NIH/CIDR. The WGHS 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. The WHI program is funded by the National Heart, Lung and Blood Institute, National Institutes of Health, US Department of Health and Human Services through contracts HHSN268201100046C, HHSN268201100001C, HHSN268201100002C, HHSN268201100003C, HHSN268201100004C, and HHSN271201100004C. Genotyping and analysis were supported through the Women's Health Initiative Sequencing Project (NHLBI RC2 HL102924), the Genetics and Epidemiology of Colorectal Cancer Consortium (NCI CA137088), the Genomics and Randomized Trials Network (NHGRI U01-HG005152), and an NCI training grant (R25CA094880). NR 56 TC 3 Z9 3 U1 7 U2 14 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0964-6906 EI 1460-2083 J9 HUM MOL GENET JI Hum. Mol. Genet. PD JAN 15 PY 2016 VL 25 IS 2 BP 358 EP 370 DI 10.1093/hmg/ddv454 PG 13 WC Biochemistry & Molecular Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Genetics & Heredity GA DG5VU UT WOS:000372148200014 PM 26561523 ER PT J AU Nelson, MI Wentworth, DE Das, SR Sreevatsan, S Killian, ML Nolting, JM Slemons, RD Bowman, AS AF Nelson, Martha I. Wentworth, David E. Das, Suman R. Sreevatsan, Srinand Killian, Mary L. Nolting, Jacqueline M. Slemons, Richard D. Bowman, Andrew S. TI Evolutionary Dynamics of Influenza A Viruses in US Exhibition Swine SO JOURNAL OF INFECTIOUS DISEASES LA English DT Article DE influenza Avirus; swine; human-animal interface; evolution; genomics; gene flow; United States; exhibition animals ID UNITED-STATES; AGRICULTURAL FAIRS; MAXIMUM-LIKELIHOOD; A(H3N2) VIRUS; OHIO; TRANSMISSION; REASSORTMENT; HUMANS; MODELS; PIGS AB The role of exhibition swine in influenza Avirus transmission was recently demonstrated by >300 infections with influenza A(H3N2) variant viruses among individuals who attended agricultural fairs. Through active influenza A virus surveillance in US exhibition swine and whole-genome sequencing of 380 isolates, we demonstrate that exhibition swine are actively involved in the evolution of influenza A viruses, including zoonotic strains. First, frequent introduction of influenza A viruses from commercial swine populations provides new genetic diversity in exhibition pigs each year locally. Second, genomic reassortment between viruses cocirculating in exhibition swine increases viral diversity. Third, viral migration between exhibition swine in neighboring states demonstrates that movements of exhibition pigs contributes to the spread of genetic diversity. The unexpected frequency of viral exchange between commercial and exhibition swine raises questions about the understudied interface between these populations. Overall, the complexity of viral evolution in exhibition swine indicates that novel viruses are likely to continually reemerge, presenting threats to humans. C1 [Nelson, Martha I.] NIH, Fogarty Int Ctr, Bldg 10, Bethesda, MD 20892 USA. [Wentworth, David E.; Das, Suman R.] Infect Dis Grp, J Craig Venter Inst, Rockville, MD USA. [Sreevatsan, Srinand] Univ Minnesota, Dept Vet Biomed Sci, St Paul, MN USA. [Sreevatsan, Srinand] Univ Minnesota, Dept Vet Populat Med, St Paul, MN USA. [Killian, Mary L.] USDA, Natl Vet Serv Labs, Ames, IA 50010 USA. [Nolting, Jacqueline M.; Slemons, Richard D.; Bowman, Andrew S.] Ohio State Univ, Dept Vet Prevent Med, Columbus, OH 43210 USA. [Wentworth, David E.] Ctr Dis Control & Prevent, Influenza Div, Virol Surveillance & Diag Branch, Atlanta, GA USA. RP Bowman, AS (reprint author), 1920 Coffey Rd, Columbus, OH USA. EM bowman.214@osu.edu OI Wentworth, David/0000-0002-5190-980X; Sreevatsan, Srinand/0000-0002-5162-2403 FU Centers of Excellence for Influenza Research and Surveillance, National Institute of Allergy and Infectious Diseases (NIAID), National Institutes of Health (NIH), Department of Health and Human Services (DHHS) [HHSN266200700007C, HHSN272201400006C]; NIAID, NIH, DHHS [HHSN272200900007C]; Multinational Influenza Seasonal Mortality Study, an ongoing international collaborative effort to understand influenza epidemiology and evolution, led by the Fogarty International Center, NIH; Office of Global Affairs at the Department of Health and Human Services; National Veterinary Services Laboratories, Animal and Plant Health Inspection Service, US Department of Agriculture FX This work was supported by the Centers of Excellence for Influenza Research and Surveillance, National Institute of Allergy and Infectious Diseases (NIAID), National Institutes of Health (NIH), Department of Health and Human Services (DHHS; contracts HHSN266200700007C and HHSN272201400006C); the NIAID, NIH, DHHS (contract HHSN272200900007C); the Multinational Influenza Seasonal Mortality Study, an ongoing international collaborative effort to understand influenza epidemiology and evolution, led by the Fogarty International Center, NIH, with funding from the Office of Global Affairs at the Department of Health and Human Services; and the National Veterinary Services Laboratories, Animal and Plant Health Inspection Service, US Department of Agriculture. 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 0022-1899 EI 1537-6613 J9 J INFECT DIS JI J. Infect. Dis. PD JAN 15 PY 2016 VL 213 IS 2 BP 173 EP 182 DI 10.1093/infdis/jiv399 PG 10 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA DF3IQ UT WOS:000371237900003 PM 26243317 ER PT J AU Zelner, JL Murray, MB Becerra, MC Galea, J Lecca, L Calderon, R Yataco, R Contreras, C Zhang, ZB Manjourides, J Grenfell, BT Cohen, T AF Zelner, Jonathan L. Murray, Megan B. Becerra, Mercedes C. Galea, Jerome Lecca, Leonid Calderon, Roger Yataco, Rosa Contreras, Carmen Zhang, Zibiao Manjourides, Justin Grenfell, Bryan T. Cohen, Ted TI Identifying Hotspots of Multidrug-Resistant Tuberculosis Transmission Using Spatial and Molecular Genetic Data SO JOURNAL OF INFECTIOUS DISEASES LA English DT Article DE drug resistance; MDR-tuberculosis; spatial analysis; tuberculosis ID MYCOBACTERIUM-TUBERCULOSIS; IDENTIFICATION; EPIDEMICS; SETTINGS; PERU AB Background. We aimed to identify and determine the etiology of "hotspots" of concentrated multidrug-resistant tuberculosis (MDR-tuberculosis) risk in Lima, Peru. Methods. From 2009 to 2012, we conducted a prospective cohort study among households of tuberculosis cases from 106 health center (HC) areas in Lima, Peru. All notified tuberculosis cases and their household contacts were followed for 1 year. Symptomatic individuals were screened by microscopy and culture; positive cultures were tested for drug susceptibility (DST) and genotyped by 24-loci mycobacterial interspersed repetitive units-variable-number tandem repeats (MIRU-VNTR). Results. 3286 individuals with culture-confirmed disease, DST, and 24-loci MIRU-VNTR were included in our analysis. Our analysis reveals: (1) heterogeneity in annual per-capita incidence of tuberculosis and MDR-tuberculosis by HC, with a rate of MDR-tuberculosis 89 times greater (95% confidence interval [CI], 54,185) in the most-affected versus the least-affected HC; (2) high risk for MDR-tuberculosis in a region spanning several HCs (odds ratio = 3.19, 95% CI, 2.33, 4.36); and (3) spatial aggregation of MDR-tuberculosis genotypes, suggesting localized transmission. Conclusions. These findings reveal that localized transmission is an important driver of the epidemic of MDR-tuberculosis in Lima. Efforts to interrupt transmission may be most effective if targeted to this area of the city. C1 [Zelner, Jonathan L.] Columbia Univ, Robert Wood Johnson Fdn, Hlth & Soc Scholars Program, Interdisciplinary Ctr Innovat Theory & Empir INCI, New York, NY USA. [Zelner, Jonathan L.] Columbia Univ, Mailman Sch Publ Hlth, New York, NY USA. [Murray, Megan B.] Harvard Univ, Sch Publ Hlth, Sch Publ Hlth, Dept Global Hlth & Social Med,Dept Epidemiol, Boston, MA 02138 USA. [Becerra, Mercedes C.] Harvard Univ, Sch Med, Dept Global Hlth & Social Med, Boston, MA 02115 USA. [Galea, Jerome; Lecca, Leonid; Calderon, Roger; Yataco, Rosa; Contreras, Carmen] Socios En Salud, Lima, Peru. [Zhang, Zibiao] Brigham & Womens Hosp, Div Global Hlth Equ, Boston, MA 02115 USA. [Manjourides, Justin] Northeastern Univ, Bouve Coll Hlth Sci, Dept Hlth Sci, Boston, MA 02115 USA. [Grenfell, Bryan T.] Princeton Univ, Dept Ecol & Evolutionary Biol, Princeton, NJ 08544 USA. [Grenfell, Bryan T.] NIH, Fogarty Int Ctr, Bldg 10, Bethesda, MD 20892 USA. [Cohen, Ted] Yale Univ, Sch Publ Hlth, Dept Epidemiol Microbial Dis, New Haven, CT USA. RP Zelner, JL (reprint author), Columbia Univ, RWJF Hlth & Soc Scholars Program, 701A Knox Hall,Mail Code 9649, New York, NY 10027 USA. EM jlz2115@columbia.edu FU Research and Policy for Infectious Disease Dynamics program of the Science and Technology Directorate, Department of Homeland Security; Fogarty International Center, National Institutes of Health (NIH); Robert Wood Johnson Foundation Health and Society Scholars program; Bill and Melinda Gates Foundation; NIH [U19 A1076217, U01 AI057786] FX This work was supported by the Research and Policy for Infectious Disease Dynamics program of the Science and Technology Directorate, Department of Homeland Security, and the Fogarty International Center, National Institutes of Health (NIH) (J. L. Z. and B. T. G.). J. L. Z. was supported by the Robert Wood Johnson Foundation Health and Society Scholars program. B. T. G. was funded by the Bill and Melinda Gates Foundation. M. B. M., M. C. B., J. G., L. L., R. C., R. Y., C. C., Z. Z., and T. C. as well as collection of all data presented were funded by the NIH (grant U19 A1076217). M. C. B., L. L., J. G., C. C., R. Y., R. C., Z. Z., and M. B. M. were also funded by grant U01 AI057786 from the NIH. NR 23 TC 4 Z9 5 U1 0 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 JAN 15 PY 2016 VL 213 IS 2 BP 287 EP 294 DI 10.1093/infdis/jiv387 PG 8 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA DF3IQ UT WOS:000371237900016 PM 26175455 ER PT J AU Sakiani, S Koh, C Heller, T AF Sakiani, Sasan Koh, Christopher Heller, Theo TI Production of False-Positive Immunoglobulin M Antibodies to Hepatitis A Virus in Autoimmune Events Reply SO JOURNAL OF INFECTIOUS DISEASES LA English DT Letter ID LIVER C1 [Sakiani, Sasan; Koh, Christopher; Heller, Theo] NIDDK, Translat Hepatol Unit, Liver Dis Branch, Natl Inst Hlth, Bethesda, MD 20892 USA. [Sakiani, Sasan] Case Western Reserve Univ, MetroHlth Med Ctr, Div Gastroenterol & Hepatol, Cleveland, OH 44106 USA. RP Sakiani, S (reprint author), MetroHlth Med Ctr, Div Gastroenterol & Hepatol, 2500 Metrohlth Dr, Cleveland, OH 44109 USA. EM ssakiani@metrohealth.org FU Intramural NIH HHS NR 6 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 JAN 15 PY 2016 VL 213 IS 2 BP 325 EP 326 DI 10.1093/infdis/jiv418 PG 2 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA DF3IQ UT WOS:000371237900021 PM 26294797 ER PT J AU Lin, YM Kazlova, V Ramakrishnan, S Murray, MA Fast, D Chandra, A Gellenbeck, KW AF Lin, Yumei Kazlova, Valentina Ramakrishnan, Shyam Murray, Mary A. Fast, David Chandra, Amitabh Gellenbeck, Kevin W. TI Bone health nutraceuticals alter microarray mRNA gene expression: A randomized, parallel, open-label clinical study SO PHYTOMEDICINE LA English DT Article DE Botanical extracts; Microarray analysis; Receptor activator of nuclear factor kappa-B; ligand; Bone morphogenetic protein 2 ID KAPPA-B LIGAND; CIRCULATING MONOCYTES; RHEUMATOID-ARTHRITIS; RECEPTOR ACTIVATOR; MINERAL DENSITY; OSTEOPOROSIS; CELLS; DISEASE; RANKL; DIFFERENTIATION AB Background and objective: Dietary intake of fruits and vegetables has been suggested to have a role in promoting bone health. More specifically, the polyphenols they contain have been linked to physiological effects related to bone mineral density and bone metabolism. In this research, we use standard microarray analyses of peripheral whole blood from post-menopausal women treated with two fixed combinations of plant extracts standardized to polyphenol content to identify differentially expressed genes relevant to bone health. Methods: In this 28-day open-label study, healthy post-menopausal women were randomized into three groups, each receiving one of three investigational fixed combinations of plant extracts: an anti-resorptive (AR) combination of pomegranate fruit (Punica granntian L) and grape seed (Vitis vim:fern L) extracts: a bone formation (BF) combination of quercetin (Dimorphandra moths Benth) and licorice (Glycyrrhiza giabra L.) extracts: and a fixed combination of all four plant extracts (AR plus BF). Standard microarray analysis was performed on peripheral whole blood samples taken before and after each treatment. Annotated genes were analyzed for their association to bone health by comparison to a gene library. Resnhs: The AR combination down-regulated a number of genes involved in reduction of bone resorption including cathepsin G (CTSG) and tachykinin receptor 1 (TACR1). The AR combination also up-regulated genes associated with formation of extracellular matrix including heparan sulfate proteoglycan 2 (HSPG2) and hyaluronoglucosaminidase 1 (HYAL1). In contrast, treatment with the BF combination resulted in up regulation of bone morphogenetic protein 2 (BMP-2) and COL1A1 (collagen type I alpha 1) genes which are linked to bone and collagen formation while down-regulating genes linked to osteoclastogenesis. Treatment with a combination of all four plant extracts had a distinctly different effect on gene expression than the results of the AR and BF combinations individually. These results could be due to multiple feedback systems balancing activities of osteoblasts and osteoclasts. Conclusion: In summary, this ex-vivo microarray study indicated that the pomegranate, grape seed, quercetin and licorice combinations of plant extracts modulated gene expression for both osteoclastic and osteogenic processes. (C) 2015 The Authors. Published by Elsevier GmbH. This is an open access article under the CC BY-NC-ND license. C1 [Lin, Yumei; Kazlova, Valentina; Ramakrishnan, Shyam; Murray, Mary A.; Gellenbeck, Kevin W.] NIH, Amway R&D, 5600 Beach Blvd, Buena Pk, CA 90622 USA. [Fast, David; Chandra, Amitabh] Access Business Grp, 7575 East Fulton Ave, Ada, MI 49355 USA. [Ramakrishnan, Shyam] Himalaya Drug Co, Tumkur Rd, Bangalore 562123, Karnataka, India. [Lin, Yumei] Yumei Consulting Inc, POB 821, Huntington Beach, CA 92648 USA. RP Gellenbeck, KW (reprint author), NIH, Amway R&D, 5600 Beach Blvd, Buena Pk, CA 90622 USA. EM kevin.gellenbeck@amway.com FU Access Business Group, LLC FX This work was funded by Access Business Group, LLC. Employees of Access Business Group LLC had a role in the design of the experiment and the interpretation of the data. NR 30 TC 2 Z9 2 U1 2 U2 3 PU ELSEVIER GMBH, URBAN & FISCHER VERLAG PI JENA PA OFFICE JENA, P O BOX 100537, 07705 JENA, GERMANY SN 0944-7113 EI 1618-095X J9 PHYTOMEDICINE JI Phytomedicine PD JAN 15 PY 2016 VL 23 IS 1 BP 18 EP 26 DI 10.1016/j.phymed.2015.11.011 PG 9 WC Plant Sciences; Chemistry, Medicinal; Integrative & Complementary Medicine; Pharmacology & Pharmacy SC Plant Sciences; Pharmacology & Pharmacy; Integrative & Complementary Medicine GA DE1VZ UT WOS:000370415900004 PM 26902403 ER PT J AU Akkaya, M Kwong, LS Akkaya, E Hatherley, D Barclay, AN AF Akkaya, Munir Kwong, Lai-Shan Akkaya, Erdem Hatherley, Deborah Barclay, A. Neil TI Rabbit CD200R binds host CD200 but not CD200-like proteins from poxviruses SO VIROLOGY LA English DT Article DE CD200; CD200R; Myxoma virus; M141; Poxviruses ID RECEPTOR FAMILY; DOWN-REGULATION; MACROPHAGE ACTIVATION; IN-VIVO; EVOLUTION; RESPONSES; HOMOLOG AB CD200 is a widely distributed membrane protein that gives inhibitory signals through its receptor (CD200R) on myeloid cells. CD200 has been acquired by herpesviruses where it has been shown to interact with host CD200R and downmodulate the immune system. It has been hypothesized that poxviruses have acquired CD200; but the potential orthologues show less similarity to their hosts. Myxoma virus M141 protein is a potential CD200 orthologue with a potent immune modulatory function in rabbits. Here, we characterized the rabbit CD200, CD200R and tested the CD200-like sequences for binding CD200R. No binding could be detected using soluble recombinant proteins, full length protein expressed on cells or myxoma virus infected cells. Finally, using knockdown models, we showed that the inhibitory effect of M141 on RAW 264.7 cells upon myxoma virus infection is not due to CD200R. We conclude that the rabbit poxvirus CD200-like proteins cause immunomodulation without utilizing CD200R. (C) 2015 The Authors. Published by Elsevier Inc. C1 [Akkaya, Munir; Kwong, Lai-Shan; Akkaya, Erdem; Hatherley, Deborah; Barclay, A. Neil] Univ Oxford, Sir William Dunn Sch Pathol, S Parks Rd, Oxford OX1 3RE, England. [Akkaya, Munir] NIAID, Immunogenet Lab, NIH, Rockville, MD 20852 USA. [Akkaya, Erdem] Hannover Med Sch, Inst Pathol, OE 5110 Carl Neuberg Str 1, D-30625 Hannover, Germany. RP Akkaya, M (reprint author), NIAID, Immunogenet Lab, NIH, Rockville, MD 20852 USA. EM munir.akkaya@nih.gov OI AKKAYA, Munir/0000-0002-9949-9424 FU Medical Research Council [G9826026] FX This work was supported by the Medical Research Council Grant no. G9826026. We are grateful to Masmudur Rahman, Sherin Smallwood and Grant McFadden for providing the recombinant virus and advice. NR 22 TC 0 Z9 0 U1 1 U2 2 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0042-6822 J9 VIROLOGY JI Virology PD JAN 15 PY 2016 VL 488 BP 1 EP 8 DI 10.1016/j.virol.2015.10.026 PG 8 WC Virology SC Virology GA DE0KJ UT WOS:000370313500001 PM 26590792 ER PT J AU Zicari, S Arakelyan, A Fitzgerald, W Zaitseva, E Chernomordik, LV Margolis, L Grivel, JC AF Zicari, Sonia Arakelyan, Anush Fitzgerald, Wendy Zaitseva, Elena Chernomordik, Leonid V. Margolis, Leonid Grivel, Jean-Charles TI Evaluation of the maturation of individual Dengue virions with flow virometry SO VIROLOGY LA English DT Article DE Dengue; Maturation; Flow virometry; prM ID MONOCLONAL-ANTIBODIES; ANTIGENIC DETERMINANTS; ENCEPHALITIS-VIRUS; PRM PROTEIN; PARTICLES; FUSION; GLYCOPROTEIN; CLEAVAGE AB High-throughput techniques are needed to analyze individual virions to understand how viral heterogeneity translates into pathogenesis since in bulk analysis the individual characteristics of virions are lost. Individual Dengue virions (DENV) undergo a maturation that involves a proteolytic cleavage of prM precursor into virion-associated M protein. Here, using a new nanoparticle-based technology, "flow virometry", we compared the maturation of individual DENV produced by BHK-21 and LoVo cells. The latter lacks the furin-protease that mediates prM cleavage. We found that prM is present on about 50% of DENV particles produced in BHK-21 cells and about 85% of DENV virions produced in LoVo, indicating an increase in the fraction of not fully matured virions. Flow virometry allows us to quantify the number of fully mature particles in DENV preparations and proves to be a useful method for studying heterogeneity of the surface proteins of various viruses. Published by Elsevier Inc. C1 [Zicari, Sonia; Arakelyan, Anush; Fitzgerald, Wendy; Margolis, Leonid] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Sect Intercellular, NIH, Bethesda, MD USA. [Zaitseva, Elena; Chernomordik, Leonid V.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Sect Membrane Biol, NIH, Bethesda, MD USA. [Grivel, Jean-Charles] Sidra Med & Res Ctr, Doha, Qatar. RP Chernomordik, LV; Margolis, L (reprint author), 10 Ctr Dr,Bldg 10,Rm-9D58, Bethesda, MD 20895 USA. EM chernoml@mail.nih.gov; margolil@helix.nih.gov FU NICHD/NIH, United States Intramural Program FX We are grateful to Dr. S. Whitehead for providing the stock of DENY. We thank Dr. Kamran Melikov for helpful discussions and Dr. Barry Alpher for correcting the English style of the text. This work was supported by the NICHD/NIH, United States Intramural Program. NR 28 TC 2 Z9 2 U1 3 U2 3 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0042-6822 J9 VIROLOGY JI Virology PD JAN 15 PY 2016 VL 488 BP 20 EP 27 DI 10.1016/j.virol.2015.10.021 PG 8 WC Virology SC Virology GA DE0KJ UT WOS:000370313500003 PM 26590794 ER PT J AU Majerciak, V Zheng, ZM AF Majerciak, Vladimir Zheng, Zhi-Ming TI Alternative RNA splicing of KSHV ORF57 produces two different RNA isoforms SO VIROLOGY LA English DT Article DE KSHV; ORF57; Alternative splicing ID LYTIC GENE-EXPRESSION; HERPESVIRUS ORF57; EXON DEFINITION; SITE SELECTION; POLYMERASE-II; SARCOMA; PROTEIN; VIRUS; POLYADENYLATION; TRANSACTIVATOR AB In lytically infected B cells Kaposi sarcoma-associated herpesvirus (KSHV) ORF57 gene encodes two RNA isoforms by alternative splicing of its pre-mRNA, which contains a small, constitutive intron in its 5' half and a large, suboptimal intron in its 3's half. The RNA1 isoform encodes full-length ORF57 and is a major isoform derived from splicing of the constitutive small intron, but retaining the suboptimal large intron as the coding region. A small fraction (<5%) of ORF57 RNA undergoes double splicing to produce a smaller non-coding RNA2 due to lack of a translational termination codon. Both RNAs are cleaved and polyadenylated at the same cleavage site CS83636. The insertion of ORF57 RNA1 into a restriction cutting site in certain mammalian expression vectors activates splicing of the subopitmal intron and produces a truncated ORF57 protein. Published by Elsevier Inc. C1 [Majerciak, Vladimir; Zheng, Zhi-Ming] NCI, Tumor Virus RNA Biol Sect, Gene Regulat & Chromosome Biol Lab, Ctr Canc Res,NIH, Frederick, MD 21702 USA. RP Zheng, ZM (reprint author), NCI, Tumor Virus RNA Biol Sect, Gene Regulat & Chromosome Biol Lab, Ctr Canc Res,NIH, Frederick, MD 21702 USA. EM zhengt@exchange.nih.gov FU Intramural Research Programs of the Center for Cancer Research, National Cancer Institute, National Institutes of Health FX This work was supported by the Intramural Research Programs of the Center for Cancer Research, National Cancer Institute, National Institutes of Health. NR 32 TC 0 Z9 0 U1 1 U2 1 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0042-6822 J9 VIROLOGY JI Virology PD JAN 15 PY 2016 VL 488 BP 81 EP 87 DI 10.1016/j.virol.2015.10.031 PG 7 WC Virology SC Virology GA DE0KJ UT WOS:000370313500011 PM 26609938 ER PT J AU Van Dis, ES Moore, TC Lavender, KJ Messer, RJ Keppler, OT Verheyen, J Dittmer, U Hasenkrug, KJ AF Van Dis, Erik S. Moore, Tyler C. Lavender, Kerry J. Messer, Ronald J. Keppler, Oliver T. Verheyen, Jens Dittmer, Ulf Hasenkrug, Kim J. TI No SEVI-mediated enhancement of rectal HIV-1 transmission of HIV-1 in two humanized mouse cohorts SO VIROLOGY LA English DT Article DE HIV; Transmission; Semen-derived enhancer of viral infection; SEVI; Amyloid; Humanized mice ID HUMAN-IMMUNODEFICIENCY-VIRUS; SEMEN-DERIVED ENHANCER; T-CELLS; TYPE-1 INFECTION; MICE; ACTIVATION; RESISTANT; CD4(+); PLASMA; QUANTITATION AB Amyloid fibrils from semen-derived peptide (SEVI) enhance HIV-1 infectivity in vitro but the ability of SEVI to mediate enhancement of HIV infection in vivo has not been tested. In this study we used immunodeficient mice reconstituted with human immune systems to test for in vivo enhancement of HIV-1 transmission. This mouse model supports mucosal transmission of HIV-1 via the intrarectal route leading to productive infection. In separate experiments with humanized mouse cohorts reconstituted with two different donor immune systems, high dose HIV-1(JR-CSF) that had been incubated with SEVI amyloid fibrils at physiologically relevant concentrations did not show an increased incidence of infection compared to controls. In addition, SEVI failed to enhance rectal transmission with a reduced concentration of HIV-1. Although we confirmed potent SEVI-mediated enhancement of HIV infectivity in vitro, this model showed no evidence that it plays a role in the much more complex situation of in vivo transmission. Published by Elsevier Inc. C1 [Van Dis, Erik S.; Moore, Tyler C.; Lavender, Kerry J.; Messer, Ronald J.; Hasenkrug, Kim J.] NIAID, Persistent Viral Dis Lab, Rocky Mt Labs, NIH, Hamilton, MT 59840 USA. [Keppler, Oliver T.] Goethe Univ Frankfurt, Inst Med Virol, Natl Reference Ctr Retroviruses, D-60054 Frankfurt, Germany. [Verheyen, Jens; Dittmer, Ulf] Univ Duisburg Essen, Univ Hosp Essen, Inst Virol, D-45122 Essen, Germany. RP Hasenkrug, KJ (reprint author), Rocky Mt Labs, 903 S 4th St, Hamilton, MT 59875 USA. EM khasenkrug@nih.gov FU Intramural Research Program of the National Institute of Allergy and Infectious Diseases of the National Institutes of Health, USA [ZIA-A1001141]; Goethe University; Robert Koch-Institute of the National Reference Center for Retroviruses; German Research Association [Transregio 60, RTG 1949] FX This work was supported by the Intramural Research Program of the National Institute of Allergy and Infectious Diseases of the National Institutes of Health, USA (ZIA-A1001141). O.T. K. acknowledges financial support from the Goethe University and from the Robert Koch-Institute of the National Reference Center for Retroviruses. U.D. acknowledges support from the German Research Association (Transregio 60 and RTG 1949). HIV-1JR-CSF was obtained through the NIH AIDS Reagent Program, Division of AIDS, NIAID, NIH: HIV-1JR-CSF from Dr. Irvin Chen. NR 34 TC 1 Z9 1 U1 0 U2 2 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0042-6822 J9 VIROLOGY JI Virology PD JAN 15 PY 2016 VL 488 BP 88 EP 95 DI 10.1016/j.virol.2015.11.005 PG 8 WC Virology SC Virology GA DE0KJ UT WOS:000370313500012 PM 26609939 ER PT J AU Welbourn, S Strebel, K AF Welbourn, Sarah Strebel, Klaus TI Low dNTP levels are necessary but may not be sufficient for lentiviral restriction by SAMHD1 SO VIROLOGY LA English DT Article DE SAMHD1; HIV-1; SIV; dATP; dNTPase; Nuclease; Restriction ID AICARDI-GOUTIERES SYNDROME; DEOXYNUCLEOSIDE TRIPHOSPHATE TRIPHOSPHOHYDROLASE; ACID BINDING-PROTEIN; CD4(+) T-CELLS; HIV-1 RESTRICTION; ALLOSTERIC ACTIVATION; NUCLEASE ACTIVITY; STRUCTURAL BASIS; DENDRITIC CELLS; INFECTION AB SAMHD1 is a cellular dNTPase that restricts lentiviral infection presumably by lowering cellular dNTP levels to below a critical threshold required for reverse transcription; however, lowering cellular dNTP levels may not be the sole mechanism of restriction. In particular, an exonuclease activity of SAMHD1 was reported to contribute to virus restriction. We further investigated the requirements for SAMHD1 restriction activity in both differentiated U937 and cycling HeLa cells. Using hydroxyurea treatment to lower baseline dNTP levels in HeLa cells, we were able to document efficient SAMHD1 restriction without significant further reduction in dNTP levels by SAMHD1. These results argue against a requirement for additional myeloid-specific host factors for SAMHD1 function but further support the notion that SAMHD1 possesses an additional dNTP-independent function contributing to lentiviral restriction. However, our own experiments failed to associate this presumed additional SAMHD1 antiviral activity with a reported nuclease activity. Published by Elsevier Inc. C1 [Welbourn, Sarah; Strebel, Klaus] NIAID, Mol Microbiol Lab, NIH, Bldg 4,Room 310,4 Ctr Dr,MSC 0460, Bethesda, MD 20892 USA. RP Strebel, K (reprint author), NIAID, Mol Microbiol Lab, NIH, Bldg 4,Room 310,4 Ctr Dr,MSC 0460, Bethesda, MD 20892 USA. EM kstrebel@nih.gov FU Intramural Research Program of the NIH, NIAID; Canadian Institutes of Health Research (C.I.H.R); Intramural AIDS Research Fellowship from NIH [1 Z01 AI000669-23 LMM] FX We thank Sandra Kao, Eri Miyagi, Chia-Yen Chen, Haruka Yoshii-Kamiyama and Sayaka Sukegawa for helpful discussions and critical reading of the manuscript and Alisha Buckler-White and Ron Plishka for sequence analysis. This work was supported in part by the Intramural Research Program of the NIH, NIAID. SW was supported by a postdoctoral fellowship from the Canadian Institutes of Health Research (C.I.H.R) and an Intramural AIDS Research Fellowship from NIH (1 Z01 AI000669-23 LMM). NR 45 TC 7 Z9 7 U1 0 U2 2 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0042-6822 J9 VIROLOGY JI Virology PD JAN 15 PY 2016 VL 488 BP 271 EP 277 DI 10.1016/j.virol.2015.11.022 PG 7 WC Virology SC Virology GA DE0KJ UT WOS:000370313500032 PM 26655245 ER PT J AU Troche, JR Mayne, ST Freedman, ND Shebl, FM Abnet, CC AF Troche, Jose Ramon Mayne, Susan T. Freedman, Neal D. Shebl, Fatma M. Abnet, Christian C. TI The Association Between Alcohol Consumption and Lung Carcinoma by Histological Subtype SO AMERICAN JOURNAL OF EPIDEMIOLOGY LA English DT Article DE alcohol consumption; cohort studies; lung cancer ID RENAL-CELL CARCINOMA; CANCER-RISK; UNITED-STATES; NEVER-SMOKERS; METAANALYSIS; COHORT; DRINKING; PATTERNS; INDEX; DIET AB Alcohol is a carcinogen suspected of increasing lung cancer risk. Therefore, we prospectively evaluated the relationship between alcohol consumption and lung carcinoma in 492,902 persons from the National Institutes of Health-AARP Diet and Health Study. We used Cox models to calculate hazard ratios and 95% confidence intervals, adjusting for tobacco smoking and other potential confounders. Between 1995/1996 and December 31, 2006, there were 10,227 incident cases of lung carcinoma, classified as adenocarcinoma (n = 4,036), squamous cell carcinoma (n = 1,998), small cell carcinoma (n = 1,524), undifferentiated carcinoma (n = 559), and other (n = 2,110). Compared with nondrinking, alcohol consumption was associated with a modest nonlinear reduction in total lung carcinoma risk at lower levels of consumption (for 0.5-< 1 drink/day, HR = 0.89, 95% confidence interval: 0.82, 0.96) but a modest increase in risk in the highest category (for = 7 drinks/day, HR = 1.11, 95% confidence interval: 1.00, 1.24). Regarding histological type, alcohol was associated with a nonlinear reduction in squamous cell carcinoma that became attenuated as consumption increased and a modest increase in adenocarcinoma among heavier drinkers. Cubic spline models confirmed these findings. Our data suggest that the relationship between alcohol consumption and lung carcinoma differs by histological subtype. C1 [Troche, Jose Ramon; Freedman, Neal D.; Abnet, Christian C.] NCI, Div Canc Epidemiol & Genet, Rockville, MD 20892 USA. [Troche, Jose Ramon; Mayne, Susan T.; Shebl, Fatma M.] Yale Univ, Sch Publ Hlth, Dept Chron Dis Epidemiol, New Haven, CT USA. [Mayne, Susan T.; Shebl, Fatma M.] Yale Canc Ctr, New Haven, CT USA. RP Troche, JR (reprint author), NCI, Div Canc Epidemiol & Genet, 9609 Med Ctr Dr, Rockville, MD 20892 USA. EM joseramon.troche@yale.edu RI Abnet, Christian/C-4111-2015 OI Abnet, Christian/0000-0002-3008-7843 FU Intramural Research Program of the National Cancer Institute and the National Institutes of Health [T32 CA105666] FX This work was supported by the Intramural Research Program of the National Cancer Institute and the National Institutes of Health (grant T32 CA105666). NR 43 TC 2 Z9 2 U1 0 U2 4 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 JAN 15 PY 2016 VL 183 IS 2 BP 110 EP 121 DI 10.1093/aje/kwv170 PG 12 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA DD5WO UT WOS:000369995600005 PM 26672017 ER PT J AU Park, SI Park, SJ Lee, J Kim, HE Park, SJ Sohn, JW Park, YG AF Park, Serk In Park, Sung-Jun Lee, Junghan Kim, Hye Eun Park, Su Jin Sohn, Jeong-Won Park, Yun Gyu TI Inhibition of cyclic AMP response element-directed transcription by decoy oligonucleotides enhances tumor-specific radiosensitivity SO BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS LA English DT Article DE Cyclic AMP response element; gamma-Irradiation; p38 MAPK; Radiosensitization; Decoy ID HUMAN-MELANOMA CELLS; BINDING PROTEIN CREB; SIGNAL-TRANSDUCTION PATHWAYS; IONIZING-RADIATION; PROSTATE-CANCER; GENE-EXPRESSION; KINASE; GROWTH; RESISTANCE; MACROPHAGES AB The radiation stress induces cytotoxic responses of cell death as well as cytoprotective responses of cell survival. Understanding exact cellular mechanism and signal transduction pathways is important in improving cancer radiotherapy. Increasing evidence suggests that cyclic AMP response element binding protein (CREB)/activating transcription factor (ATF) family proteins act as a survival factor and a signaling molecule in response to stress. We postulated that CREB inhibition via CRE decoy oligonucleotide increases tumor cell sensitization to gamma-irradiation-induced cytotoxic stress. In the present study, we demonstrate that CREB phosphorylation and CREB DNA-protein complex formation increased in time and radiation dose-dependent manners, while there was no significant change in total protein level of CREB. In addition, CREB was phosphorylated in response to gamma-irradiation through p38 MAPK pathway. Further investigation revealed that CREB blockade by decoy oligonucleotides functionally inhibited transactivation of CREB, and significantly increased radiosensitivity of multiple human cancer cell lines including TP53- and/or RB-mutated cells with minimal effects on normal cells. We also demonstrate that tumor cells ectopically expressing dominant negative mutant CREB (KCREB) and the cells treated with p38 MAPK inhibitors were more sensitive to gamma-irradiation than wild type parental cells or control-treated cells. Taken together, we conclude that CREB protects tumor cells from gamma-irradiation, and combination of CREB inhibition plus ionizing radiation will be a promising radiotherapeutic approach. (C) 2015 Elsevier Inc. All rights reserved. C1 [Park, Serk In; Park, Sung-Jun; Lee, Junghan; Kim, Hye Eun; Park, Su Jin; Sohn, Jeong-Won; Park, Yun Gyu] Korea Univ, Coll Med, Dept Biochem & Mol Biol, Seoul 136705, South Korea. [Park, Serk In] Korea Univ, Coll Med, Plus Program Biomed Sci BK21, Seoul 136705, South Korea. [Park, Serk In] Vanderbilt Univ, Sch Med, Dept Med, Nashville, TN 37212 USA. [Park, Serk In] Vanderbilt Univ, Sch Med, Ctr Bone Biol, Nashville, TN 37212 USA. [Park, Sung-Jun] NHLBI, Lab Obes & Aging Res, NIH, Bldg 10, Bethesda, MD 20892 USA. RP Park, SI; Park, YG (reprint author), Munsuk Med Hall Room 319,73 Inchon Ro, Seoul 02841, South Korea. EM serkin@korea.edu; parkyg@korea.ac.kr OI Park, Serk In/0000-0001-8643-5096 FU Korea University Research Grant [K1512691]; National Research Foundation of the Korean Government (MSIP) [2015R1C1A1A01051508] FX This work was financially supported by the Korea University Research Grant (K1512691 to S.I.P.), and the National Research Foundation of the Korean Government (MSIP, Grant No. 2015R1C1A1A01051508 to S.I.P.). NR 33 TC 1 Z9 1 U1 0 U2 2 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0006-291X EI 1090-2104 J9 BIOCHEM BIOPH RES CO JI Biochem. Biophys. Res. Commun. PD JAN 15 PY 2016 VL 469 IS 3 BP 363 EP 369 DI 10.1016/j.bbrc.2015.11.122 PG 7 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA DC6TP UT WOS:000369352800006 PM 26655813 ER PT J AU Wei, Z Angerer, LM Angerer, RC AF Wei, Zheng Angerer, Lynne M. Angerer, Robert C. TI Neurogenic gene regulatory pathways in the sea urchin embryo SO DEVELOPMENT LA English DT Article DE Sea urchin; Strongylocentrotus purpuratus; Neurogenesis; Embryogenesis; SoxC; Brn1/2/4; Six3 ID NERVOUS-SYSTEM; FACTOR BRN-2; EXPRESSION; DOMAIN; NEURONS; SPECIFICATION; HYPOTHALAMUS; PROTEINS; PATTERNS; CELLS AB During embryogenesis the sea urchin early pluteus larva differentiates 40-50 neurons marked by expression of the panneural marker synaptotagmin B (SynB) that are distributed along the ciliary band, in the apical plate and pharyngeal endoderm, and 4-6 serotonergic neurons that are confined to the apical plate. Development of all neurons has been shown to depend on the function of Six3. Using a combination of molecular screens and tests of gene function by morpholino-mediated knockdown, we identified SoxC and Brn1/2/4, which function sequentially in the neurogenic regulatory pathway and are also required for the differentiation of all neurons. Misexpression of Brn1/2/4 at low dose caused an increase in the number of serotonin-expressing cells and at higher dose converted most of the embryo to a neurogenic epithelial sphere expressing the Hnf6 ciliary band marker. A third factor, Z167, was shown to work downstream of the Six3 and SoxC core factors and to define a branch specific for the differentiation of serotonergic neurons. These results provide a framework for building a gene regulatory network for neurogenesis in the sea urchin embryo. C1 [Wei, Zheng; Angerer, Lynne M.; Angerer, Robert C.] Natl Inst Dent & Craniofacial Res, NIH, Bethesda, MD 20892 USA. RP Angerer, RC (reprint author), Natl Inst Dent & Craniofacial Res, NIH, Bethesda, MD 20892 USA. EM rang@mail.nih.gov FU Intramural Research Program of the National Institutes of Health, NIDCR [ZO1DE000712] FX This work was supported by a grant [ZO1DE000712] from the Intramural Research Program of the National Institutes of Health, NIDCR. Deposited in PMC for release after 12 months. NR 40 TC 4 Z9 4 U1 6 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 JAN 15 PY 2016 VL 143 IS 2 BP 298 EP 305 DI 10.1242/dev.125989 PG 8 WC Developmental Biology SC Developmental Biology GA DC8WJ UT WOS:000369500200012 PM 26657764 ER PT J AU Ahmad, SM Bhattacharyya, P Jeffries, N Gisselbrecht, SS Michelson, AM AF Ahmad, Shaad M. Bhattacharyya, Pritha Jeffries, Neal Gisselbrecht, Stephen S. Michelson, Alan M. TI Two Forkhead transcription factors regulate cardiac progenitor specification by controlling the expression of receptors of the fibroblast growth factor and Wnt signaling pathways SO DEVELOPMENT LA English DT Article DE Forkhead domain transcription factors; Signaling pathway receptors; Fibroblast growth factor receptor; Wnt signaling pathway receptors; Gene regulation; Cardiac progenitor specification; Cardiac mesoderm specification; Heart development; Cardiogenesis; Organogenesis ID DROSOPHILA FGF-RECEPTOR; EMBRYONIC-DEVELOPMENT; MESODERMAL CELLS; TRANSGENIC RNAI; GENE-EXPRESSION; HEART; WINGLESS; DIVISION; GENOME; TARGET AB Cardiogenesis involves the coordinated regulation of multiple biological processes by a finite set of transcription factors (TFs). Here, we show that the Forkhead TFs Checkpoint suppressor homologue (CHES-1-like) and Jumeau (Jumu), which govern cardiac progenitor cell divisions by regulating Polo kinase activity, play an additional, mutually redundant role in specifying the cardiac mesoderm (CM) as eliminating the functions of both Forkhead genes in the same Drosophila embryo results in defective hearts with missing hemisegments. This process is mediated by the Forkhead TFs regulating the fibroblast growth factor receptor Heartless (Htl) and the Wnt receptor Frizzled (Fz): CHES-1-like and jumu exhibit synergistic genetic interactions with htl and fz in CM specification, thereby implying that they function through the same genetic pathways, and transcriptionally activate the expression of both receptor-encoding genes. Furthermore, ectopic overexpression of either htl or fz in the mesoderm partially rescues the defective CM specification phenotype in embryos lacking both Forkhead genes. Together, these data emphasize the functional redundancy that leads to robustness in the cardiac progenitor specification process, and illustrate the pleiotropic functions of Forkhead TFs in different aspects of cardiogenesis. C1 [Ahmad, Shaad M.] Indiana State Univ, Dept Biol, Terre Haute, IN 47809 USA. [Ahmad, Shaad M.] Indiana State Univ, Ctr Genom Advocacy, Terre Haute, IN 47809 USA. [Ahmad, Shaad M.; Bhattacharyya, Pritha; Michelson, Alan M.] NHLBI, Lab Dev Syst Biol, NIH, Bethesda, MD 20892 USA. [Jeffries, Neal] NHLBI, Off Biostat Res, NIH, Bethesda, MD 20892 USA. [Gisselbrecht, Stephen S.] Brigham & Womens Hosp, Dept Med, Div Genet, Boston, MA 02115 USA. [Gisselbrecht, Stephen S.] Harvard Univ, Sch Med, Boston, MA 02115 USA. RP Ahmad, SM (reprint author), Indiana State Univ, Dept Biol, Terre Haute, IN 47809 USA.; Ahmad, SM (reprint author), Indiana State Univ, Ctr Genom Advocacy, Terre Haute, IN 47809 USA.; Ahmad, SM; Michelson, AM (reprint author), NHLBI, Lab Dev Syst Biol, NIH, Bethesda, MD 20892 USA. EM Shaad.Ahmad@indstate.edu; michelsonam@nhlbi.nih.gov OI Ahmad, Shaad/0000-0001-5373-1710; Gisselbrecht, Stephen/0000-0001-8723-902X FU National Heart, Lung, and Blood Institute (NHLBI) Division of Intramural Research FX This work was supported by the National Heart, Lung, and Blood Institute (NHLBI) Division of Intramural Research (A.M.M.). Deposited in PMC for immediate release. NR 57 TC 0 Z9 0 U1 4 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 JAN 15 PY 2016 VL 143 IS 2 BP 306 EP 317 DI 10.1242/dev.122952 PG 12 WC Developmental Biology SC Developmental Biology GA DC8WJ UT WOS:000369500200013 PM 26657774 ER PT J AU Wexler, P Judson, R de Marcellus, S de Knecht, J Leinala, E AF Wexler, Philip Judson, Richard de Marcellus, Sally de Knecht, Joop Leinala, Eeva TI Health effects of toxicants: Online knowledge support SO LIFE SCIENCES LA English DT Article DE Toxicology; Computerized information; Databases; Toxicity; Environmental health; Toxicoinformatics; National Library of Medicine; US Environmental Protection Agency; OECD; Toxicology information; Chemical databases; Hazardous chemicals; Toxicology information; Toxicology databases; Environmental health database; Online toxicology information; Online toxicology resources ID COMPUTATIONAL TOXICOLOGY RESOURCE; NATIONAL-LIBRARY; ENVIRONMENTAL-HEALTH; INFORMATION; TOXICITY; DATABASE; PROGRAM; ACTOR AB Research in toxicology generates vast quantities of data which reside on the Web and are subsequently appropriated and utilized to support further research. This data includes a broad spectrum of information about chemical, biological and radiological agents which can affect health, the nature of the effects, treatment, regulatory measures, and more. Information is structured in a variety of formats, including traditional databases, portals, prediction models, and decision making support tools. Online resources are created and housed by a variety of institutions, including libraries and government agencies. This paper focuses on three such institutions and the tools they offer to the public: the National Library of Medicine (NLM) and its Toxicology and Environmental Health Information Program, the United States Environmental Protection Agency (EPA), and the Organisation for Economic Co-operation and Development (OECD). Reference is also made to other relevant organizations. Published by Elsevier Inc. C1 [Wexler, Philip] Natl Lib Med, Toxicol & Environm Hlth Informat Program, Bethesda, MD 20894 USA. [Judson, Richard] US EPA, Washington, DC USA. [de Marcellus, Sally; de Knecht, Joop; Leinala, Eeva] OECD, Environm Directorate, Environm Hlth & Safety Div, Paris, France. RP Wexler, P (reprint author), Natl Lib Med, Toxicol & Environm Hlth Informat Program, Bethesda, MD 20894 USA. OI Wexler, Philip/0000-0001-7240-7721 FU Intramural Research Program of the National Institutes of Health, National Library of Medicine FX This paper was supported by the Intramural Research Program of the National Institutes of Health, National Library of Medicine. NR 20 TC 0 Z9 0 U1 0 U2 3 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0024-3205 EI 1879-0631 J9 LIFE SCI JI Life Sci. PD JAN 15 PY 2016 VL 145 BP 284 EP 293 DI 10.1016/j.lfs.2015.10.002 PG 10 WC Medicine, Research & Experimental; Pharmacology & Pharmacy SC Research & Experimental Medicine; Pharmacology & Pharmacy GA DC7AG UT WOS:000369370100034 PM 26506572 ER PT J AU Tae, HJ Petrashevskaya, N Marshall, S Krawczyk, M Talan, M AF Tae, Hyun-Jin Petrashevskaya, Natalia Marshall, Shannon Krawczyk, Melissa Talan, Mark TI Cardiac remodeling in the mouse model of Marfan syndrome develops into two distinctive phenotypes SO AMERICAN JOURNAL OF PHYSIOLOGY-HEART AND CIRCULATORY PHYSIOLOGY LA English DT Article DE fibrillin-1; Marfan syndrome; myocardial hypertrophy; cardiac function ID LEFT-VENTRICULAR FUNCTION; AXIS SYSTOLIC FUNCTION; AORTIC-ANEURYSM; HEART-FAILURE; MICE; PATHOGENESIS; IMPAIRMENT; ACTIVATION; MUTATIONS; PRESSURE AB Marfan syndrome (MFS) is a systemic disorder of connective tissue caused by mutations in fibrillin-1. Cardiac dysfunction in MFS has not been characterized halting the development of therapies of cardiac complication in MFS. We aimed to study the age-dependent cardiac remodeling in the mouse model of MFS FbnC1039G(-/-) mouse [Marfan heterozygous (HT) mouse] and its association with valvular regurgitation. Marfan HT mice of 2-4 mo demonstrated a mild hypertrophic cardiac remodeling with predominant decline of diastolic function and increased transforming growth factor-beta canonical (p-SMAD2/3) and noncanonical (pERK1/2 and p-p38 MAPK) signaling and upregulation of hypertrophic markers natriuretic peptides atrium natriuretic peptide and brain natriuretic peptide. Among older HT mice (6-14 mo), cardiac remodeling was associated with two distinct phenotypes, manifesting either dilated or constricted left ventricular chamber. Dilatation of left ventricular chamber was accompanied by biochemical evidence of greater mechanical stress, including elevated ERK1/2 and p38 MAPK phosphorylation and higher brain natriuretic peptide expression. The aortic valve regurgitation was registered in 20% of the constricted group and 60% of the dilated group, whereas mitral insufficiency was observed in 40% of the constricted group and 100% of the dilated group. Cardiac dysfunction was not associated with the increase of interstitial fibrosis and nonmyocyte proliferation. In the mouse model fibrillin-1, haploinsufficiency results in the early onset of nonfibrotic hypertrophic cardiac remodeling and dysfunction, independently from valvular abnormalities. MFS heart is vulnerable to stress-induced cardiac dilatation in the face of valvular regurgitation, and stress-activated MAPK signals represent a potential target for cardiac management in MFS. C1 [Tae, Hyun-Jin; Petrashevskaya, Natalia; Marshall, Shannon; Krawczyk, Melissa; Talan, Mark] NIA, Cardiovasc Sci Lab, NIH, Baltimore, MD 21224 USA. RP Petrashevskaya, N (reprint author), NIA, Cardiovasc Sci Lab, Intramural Res Program, NIH,Biomed Res Ctr, 251 Bayview Blvd, Baltimore, MD 21224 USA. EM petrashevskayn@mail.nih.gov FU Intramural Research Program of the National Institute on Aging, National Institutes of Health FX This research was fully supported by the Intramural Research Program of the National Institute on Aging, National Institutes of Health. NR 41 TC 2 Z9 2 U1 1 U2 4 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0363-6135 EI 1522-1539 J9 AM J PHYSIOL-HEART C JI Am. J. Physiol.-Heart Circul. Physiol. PD JAN 15 PY 2016 VL 310 IS 2 BP H290 EP H299 DI 10.1152/ajpheart.00354.2015 PG 10 WC Cardiac & Cardiovascular Systems; Physiology; Peripheral Vascular Disease SC Cardiovascular System & Cardiology; Physiology GA DC2OS UT WOS:000369056600014 PM 26566724 ER PT J AU Awad, KS Elinoff, JM Wang, SB Gairhe, S Ferreyra, GA Cai, RM Sun, JF Solomon, MA Danner, RL AF Awad, Keytam S. Elinoff, Jason M. Wang, Shuibang Gairhe, Salina Ferreyra, Gabriela A. Cai, Rongman Sun, Junfeng Solomon, Michael A. Danner, Robert L. TI Raf/ERK drives the proliferative and invasive phenotype of BMPR2-silenced pulmonary artery endothelial cells SO AMERICAN JOURNAL OF PHYSIOLOGY-LUNG CELLULAR AND MOLECULAR PHYSIOLOGY LA English DT Article DE pulmonary arterial hypertension; BMPR2; endothelial cell dysfunction; nintedanib ID MORPHOGENETIC PROTEIN-RECEPTOR; II RECEPTOR; BMPR-II; MULTIKINASE INHIBITOR; PLEXIFORM LESIONS; HYPERTENSION; EXPRESSION; MUTATIONS; APOPTOSIS; SURVIVAL AB Awad KS, Elinoff JM, Wang S, Gairhe S, Ferreyra GA, Cai R, Sun J, Solomon MA, Danner RL. Raf/ERK drives the proliferative and invasive phenotype of BMPR2-silenced pulmonary artery endothelial cells. Am J Physiol Lung Cell Mol Physiol 310: L187-L201, 2016. First published November 20, 2015; doi:10.1152/ajplung. 00303.2015.-A proliferative endothelial cell phenotype, inflammation, and pulmonary vascular remodeling are prominent features of pulmonary arterial hypertension (PAH). Bone morphogenetic protein type II receptor (BMPR2) loss-of-function is the most common cause of heritable PAH and has been closely linked to the formation of pathological plexiform lesions. Although some BMPR2 mutations leave ligand-dependent responses intact, the disruption of ligand-independent, noncanonical functions are universal among PAH-associated BMPR2 genotypes, but incompletely understood. This study examined the noncanonical signaling consequences of BMPR2 silencing in human pulmonary artery endothelial cells to identify potential therapeutic targets. BMPR2 siRNA silencing resulted in a proliferative, promigratory pulmonary artery endothelial cell phenotype and disruption of cytoskeletal architecture. Expression profiling closely reflected these phenotypic changes. Gene set enrichment and promoter analyses, as well as the differential expression of pathway components identified Ras/Raf/ERK signaling as an important consequence of BMPR2 silencing. Raf family members and ERK1/2 were constitutively activated after BMPR2 knockdown. Two Raf inhibitors, sorafenib and AZ628, and low-dose nintedanib, a triple receptor tyrosine kinase inhibitor upstream from Ras, reversed the abnormal proliferation and hypermotility of BMPR2 deficiency. Inhibition of dysregulated Ras/Raf/ERK signaling may be useful in reversing vascular remodeling in PAH. C1 [Awad, Keytam S.; Elinoff, Jason M.; Wang, Shuibang; Gairhe, Salina; Ferreyra, Gabriela A.; Cai, Rongman; Sun, Junfeng; Solomon, Michael A.; Danner, Robert L.] NIH, Crit Care Med Dept, Ctr Clin, Bldg 10, Bethesda, MD 20892 USA. [Solomon, Michael A.] NHLBI, Cardiopulm Branch, NIH, Bldg 10, Bethesda, MD 20892 USA. RP Elinoff, JM (reprint author), NIH, Dept Crit Care Med, 10 Ctr Dr,Rm 2C145, Bethesda, MD 20892 USA. EM elinoffj@cc.nih.gov FU intramural National Institutes of Health (NIH) funds; NIH Office of Women's Health FX This study was supported through intramural National Institutes of Health (NIH) funds, including a 2011-2013 Bench to Bedside Award from the NIH Office of Women's Health. NR 64 TC 4 Z9 4 U1 0 U2 2 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 1040-0605 EI 1522-1504 J9 AM J PHYSIOL-LUNG C JI Am. J. Physiol.-Lung Cell. Mol. Physiol. PD JAN 15 PY 2016 VL 310 IS 2 BP L187 EP L201 DI 10.1152/ajplung.00303.2015 PG 15 WC Physiology; Respiratory System SC Physiology; Respiratory System GA DC2NI UT WOS:000369053000009 PM 26589479 ER PT J AU Thompson, LC Holland, NA Snyder, RJ Luo, B Becak, DP Odom, JT Harrison, BS Brown, JM Gowdy, KM Wingard, CJ AF Thompson, Leslie C. Holland, Nathan A. Snyder, Ryan J. Luo, Bin Becak, Daniel P. Odom, Jillian T. Harrison, Benjamin S. Brown, Jared M. Gowdy, Kymberly M. Wingard, Christopher J. TI Pulmonary instillation of MWCNT increases lung permeability, decreases gp130 expression in the lungs, and initiates cardiovascular IL-6 transsignaling SO AMERICAN JOURNAL OF PHYSIOLOGY-LUNG CELLULAR AND MOLECULAR PHYSIOLOGY LA English DT Article DE blood vessels; carbon nanotubes; endothelium; soluble IL-6 receptor ID WALLED CARBON NANOTUBES; NF-KAPPA-B; AIRWAY EPITHELIAL-CELLS; CARDIAC ISCHEMIA/REPERFUSION INJURY; ALVEOLAR-CAPILLARY COCULTURE; SPRAGUE-DAWLEY RATS; IN-VIVO; ADHESION MOLECULE-1; ENDOTHELIAL-CELLS; TIGHT JUNCTIONS AB Thompson LC, Holland NA, Snyder RJ, Luo B, Becak DP, Odom JT, Harrison BS, Brown JM, Gowdy KM, Wingard CJ. Pulmonary instillation of MWCNT increases lung permeability, decreases gp130 expression in the lungs, and initiates cardiovascular IL-6 transsignaling. Am J Physiol Lung Cell Mol Physiol 310: L142-L154, 2016. First published November 20, 2015; doi:10.1152/ajplung. 00384.2014.-Pulmonary instillation of multiwalled carbon nanotubes ( MWCNT) has the potential to promote cardiovascular derangements, but the mechanisms responsible are currently unclear. We hypothesized that exposure to MWCNT would result in increased epithelial barrier permeability by 24 h postexposure and initiate a signaling process involving IL-6/gp130 transsignaling in peripheral vascular tissue. To test this hypothesis we assessed the impact of 1 and 10 mu g/cm(2) MWCNT on transepithelial electrical resistance (TEER) and expression of barrier proteins and cell activation in vitro using normal human bronchial epithelial primary cells. Parallel studies using male Sprague-Dawley rats instilled with 100 mu g MWCNT measured bronchoalveolar lavage (BAL) differential cell counts, BAL fluid total protein, and lung water-to-tissue weight ratios 24 h postexposure and quantified serum concentrations of IL-6, soluble IL-6r, and soluble gp130. Aortic sections were examined immunohistochemically for gp130 expression, and gp130 mRNA/protein expression was evaluated in rat lung, heart, and aortic tissue homogenates. Our in vitro findings indicate that 10 mu g/cm(2) MWCNT decreased the development of TEER and zonula occludens-1 expression relative to the vehicle. In rats MWCNT instillation increased BAL protein, lung water, and induced pulmonary eosinophilia. Serum concentrations of soluble gp130 decreased, aortic endothelial expression of gp130 increased, and expression of gp130 in the lung was downregulated in the MWCNT-exposed group. We propose that pulmonary exposure to MWCNT can manifest as a reduced epithelial barrier and activator of vascular gp130-associated transsignaling that may promote susceptibility to cardiovascular derangements. C1 [Thompson, Leslie C.; Holland, Nathan A.; Becak, Daniel P.; Odom, Jillian T.; Wingard, Christopher J.] E Carolina Univ, Brody Sch Med, Dept Physiol, Greenville, NC 27834 USA. [Luo, Bin; Brown, Jared M.; Gowdy, Kymberly M.] E Carolina Univ, Brody Sch Med, Dept Pharmacol & Toxicol, Greenville, NC USA. [Snyder, Ryan J.] NIEHS, NanoHlth Program, NIH, POB 12233, Res Triangle Pk, NC 27709 USA. [Harrison, Benjamin S.] Wake Forest Univ, Inst Regenerat Med, Winston Salem, NC 27109 USA. RP Wingard, CJ (reprint author), E Carolina Univ, Brody Sch Med, Dept Physiol, Greenville, NC 27834 USA. EM wingardc@ecu.edu OI Wingard, Christopher/0000-0002-8251-5678 FU NIEHS NIH HHS [R01 ES016246, U19 ES019525] NR 70 TC 2 Z9 2 U1 2 U2 7 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 1040-0605 EI 1522-1504 J9 AM J PHYSIOL-LUNG C JI Am. J. Physiol.-Lung Cell. Mol. Physiol. PD JAN 15 PY 2016 VL 310 IS 2 BP L142 EP L154 DI 10.1152/ajplung.00384.2014 PG 13 WC Physiology; Respiratory System SC Physiology; Respiratory System GA DC2NI UT WOS:000369053000005 PM 26589480 ER PT J AU Adelman, K Scruggs, BS Henriques, T Burkholder, A Fargo, DC AF Adelman, Karen Scruggs, Benjamin S. Henriques, Telmo Burkholder, Adam Fargo, David C. TI Regulating transcription elongation at stimulus responsive genes SO CANCER RESEARCH LA English DT Meeting Abstract CT American-Association-for-Cancer-Research (AACR) Special Conference on Chromatin and Epigenetics in Cancer CY SEP 24-27, 2015 CL Atlanta, GA SP Amer Assoc Canc Res C1 [Adelman, Karen; Scruggs, Benjamin S.; Henriques, Telmo] 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. 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 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD JAN 15 PY 2016 VL 76 SU 2 MA IA10 DI 10.1158/1538-7445.CHROMEPI15-IA10 PG 2 WC Oncology SC Oncology GA DC0TN UT WOS:000368930800054 ER PT J AU Dickherber, T AF Dickherber, Tony TI Innovative technologies for cancer research - NCI Strategy for supporting next generation of tools needed against cancer SO CANCER RESEARCH LA English DT Meeting Abstract CT American-Association-for-Cancer-Research (AACR) Special Conference on Chromatin and Epigenetics in Cancer CY SEP 24-27, 2015 CL Atlanta, GA SP Amer Assoc Canc Res C1 [Dickherber, Tony] NCI, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 1 U2 1 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 JAN 15 PY 2016 VL 76 SU 2 MA A35 DI 10.1158/1538-7445.CHROMEPI15-A35 PG 2 WC Oncology SC Oncology GA DC0TN UT WOS:000368930800022 ER PT J AU Nickerson, M Im, KM Guo, GW Gui, YT Turan, S Costello, JC Zhou, Q Cai, ZM Wu, S Lucia, MS Moore, LE Dean, M Theodorescu, D AF Nickerson, Mike Im, Kate M. Guo, Guangwu Gui, Yaoting Turan, Sevilay Costello, James C. Zhou, Quan Cai, Zhiming Wu, Song Lucia, M. Scott Moore, Lee E. Dean, Michael Theodorescu, Dan TI Gene alterations associated with clinical characteristics of bladder cancer SO CANCER RESEARCH LA English DT Meeting Abstract CT American-Association-for-Cancer-Research (AACR) Special Conference on Chromatin and Epigenetics in Cancer CY SEP 24-27, 2015 CL Atlanta, GA SP Amer Assoc Canc Res C1 [Nickerson, Mike; Turan, Sevilay; Dean, Michael] NCI, Frederick, MD 21701 USA. [Im, Kate M.; Zhou, Quan] Data Sci Genom, Ellicott City, MD USA. [Guo, Guangwu] Beijing Genome Inst Shenzhen, Shenzhen, Peoples R China. [Gui, Yaoting] Peking Univ, Shenzhen Hosp, Shenzhen, Peoples R China. [Costello, James C.; Lucia, M. Scott; Theodorescu, Dan] Univ Colorado, Aurora, CO USA. [Cai, Zhiming; Wu, Song] Shenzhen Second Peoples Hosp, Shenzhen, Peoples R China. [Moore, Lee E.] NCI, Rockville, MD USA. NR 0 TC 0 Z9 0 U1 3 U2 7 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD JAN 15 PY 2016 VL 76 SU 2 MA A52 DI 10.1158/1538-7445.CHROMEPI15-A52 PG 3 WC Oncology SC Oncology GA DC0TN UT WOS:000368930800031 ER PT J AU Zhang, SF Zhu, I Deng, T Furusawa, T Landsman, D Bustin, M AF Zhang, Shaofei Zhu, Iris Deng, Tao Furusawa, Takashi Landsman, David Bustin, Michael TI High mobility group N proteins modulate chromatin regulatory sites and gene expression during LPS-induced B-cell activation SO CANCER RESEARCH LA English DT Meeting Abstract CT American-Association-for-Cancer-Research (AACR) Special Conference on Chromatin and Epigenetics in Cancer CY SEP 24-27, 2015 CL Atlanta, GA SP Amer Assoc Canc Res C1 [Zhang, Shaofei; Zhu, Iris; Deng, Tao; Furusawa, Takashi; Landsman, David; Bustin, Michael] NIH, Bldg 10, Bethesda, MD 20892 USA. RI Bustin, Michael/G-6155-2015 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 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD JAN 15 PY 2016 VL 76 SU 2 MA A23 DI 10.1158/1538-7445.CHROMEPI15-A23 PG 2 WC Oncology SC Oncology GA DC0TN UT WOS:000368930800014 ER PT J AU Yang, JC AF Yang, James C. TI The Immunotherapy Roadmap SO CLINICAL CANCER RESEARCH LA English DT Editorial Material ID PD-1 BLOCKADE; CANCER; MELANOMA AB As new active agents are discovered and approved, it is clear that combinations of these immunotherapies will be needed to reject most human cancers. The era of personalized patient tumor analysis has arrived just in time to guide these combinations. (C) 2015 AACR. C1 [Yang, James C.] NCI, Surg Branch, 9000 Rockville Pike,Bldg 10 CRC,Rm 3-5952, Bethesda, MD 20892 USA. RP Yang, JC (reprint author), NCI, Surg Branch, 9000 Rockville Pike,Bldg 10 CRC,Rm 3-5952, Bethesda, MD 20892 USA. EM jamesyang@mail.nih.gov FU Intramural NIH HHS [Z99 CA999999] NR 10 TC 0 Z9 0 U1 0 U2 9 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1078-0432 EI 1557-3265 J9 CLIN CANCER RES JI Clin. Cancer Res. PD JAN 15 PY 2016 VL 22 IS 2 BP 275 EP 276 DI 10.1158/1078-0432.CCR-15-2144 PG 2 WC Oncology SC Oncology GA DC2VP UT WOS:000369076500002 PM 26459176 ER PT J AU Eiden, AM Zhang, SL Gary, JM Simmons, JK Mock, BA AF Eiden, Adrian M. Zhang, Shuling Gary, Joy M. Simmons, John K. Mock, Beverly A. TI Molecular Pathways: Increased Susceptibility to Infection Is a Complication of mTOR Inhibitor Use in Cancer Therapy SO CLINICAL CANCER RESEARCH LA English DT Article ID T-CELL DIFFERENTIATION; BREAST-CANCER; IMMUNE-RESPONSES; RAPAMYCIN AY-22,989; DEPENDENT FASHION; MAMMALIAN PROTEIN; ADVERSE EVENTS; COMPLEX; EVEROLIMUS; MUTATIONS AB As one of the earliest examples of "chemical biology," the Mechanistic Target of Rapamycin (mTOR) protein and its chemical inhibitors have been extensively studied across a spectrum of physiologic and pathologic processes at the molecular, organismal, and patient population levels. There are several FDA-approved mTOR inhibitors (sirolimus, everolimus, and temsirolimus) with indications for cancer treatment and for prevention of solid organ rejection. Dozens of mTOR inhibitors are currently being evaluated in hundreds of ongoing clinical trials across a spectrum of diseases, including numerous cancer indications, autoimmune diseases, and a number of congenital disorders. As many of the approved and investigational indications for mTOR inhibitors require long-term treatment, the magnitude and incidence of particular side effects differ from those observed in shorter-term treatments. Here, we focus on the increased risk of infections in patients being treated with mTOR inhibitors. While increased infection rates might be expected from a class of drugs approved as posttransplant immunosuppressants, we review reports from clinical, mechanistic, and genetically engineered mouse model studies detailing a much more nuanced view of mTOR inhibitor drug action and target biology. (C) 2015 AACR. C1 [Eiden, Adrian M.; Zhang, Shuling; Gary, Joy M.; Simmons, John K.; Mock, Beverly A.] NCI, Lab Canc Biol & Genet, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. RP Mock, BA (reprint author), NCI, NIH, Bldg 37,Rm 3146,37 Convent Dr,MSC 4258, Bethesda, MD 20892 USA. EM mockb@mail.nih.gov FU Intramural Research Program of the NIH, NCI, Center for Cancer Research FX This work was supported by the Intramural Research Program of the NIH, NCI, Center for Cancer Research. NR 73 TC 1 Z9 1 U1 1 U2 2 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1078-0432 EI 1557-3265 J9 CLIN CANCER RES JI Clin. Cancer Res. PD JAN 15 PY 2016 VL 22 IS 2 BP 277 EP 283 DI 10.1158/1078-0432.CCR-14-3239 PG 7 WC Oncology SC Oncology GA DC2VP UT WOS:000369076500003 PM 26607598 ER PT J AU Yankeelov, TE Mankoff, DA Schwartz, LH Lieberman, FS Buatti, JM Mountz, JM Erickson, BJ Fennessy, FMM Huang, W Kalpathy-Cramer, J Wahl, RL Linden, HM Kinahan, PE Zhao, BS Hylton, NM Gillies, RJ Clarke, L Nordstrom, R Rubin, DL AF Yankeelov, Thomas E. Mankoff, David A. Schwartz, Lawrence H. Lieberman, Frank S. Buatti, John M. Mountz, James M. Erickson, Bradley J. Fennessy, Fiona M. M. Huang, Wei Kalpathy-Cramer, Jayashree Wahl, Richard L. Linden, Hannah M. Kinahan, Paul E. Zhao, Binsheng Hylton, Nola M. Gillies, Robert J. Clarke, Laurence Nordstrom, Robert Rubin, Daniel L. TI Quantitative Imaging in Cancer Clinical Trials SO CLINICAL CANCER RESEARCH LA English DT Review ID POSITRON-EMISSION-TOMOGRAPHY; TUMOR RESPONSE; APPARENT DIFFUSION; LUNG-CANCER; VOLUME; PET; INFRASTRUCTURE; WHITEPAPERS; ONCOLOGY; CRITERIA AB As anticancer therapies designed to target specific molecular pathways have been developed, it has become critical to develop methods to assess the response induced by such agents. Although traditional, anatomic CT, and MRI examinations are useful in many settings, increasing evidence suggests that these methods cannot answer the fundamental biologic and physiologic questions essential for assessment and, eventually, prediction of treatment response in the clinical trial setting, especially in the critical period soon after treatment is initiated. To optimally apply advances in quantitative imaging methods to trials of targeted cancer therapy, new infrastructure improvements are needed that incorporate these emerging techniques into the settings where they are most likely to have impact. In this review, we first elucidate the needs for therapeutic response assessment in the era of molecularly targeted therapy and describe how quantitative imaging can most effectively provide scientifically and clinically relevant data. We then describe the tools and methods required to apply quantitative imaging and provide concrete examples of work making these advances practically available for routine application in clinical trials. We conclude by proposing strategies to surmount barriers to wider incorporation of these quantitative imaging methods into clinical trials and, eventually, clinical practice. Our goal is to encourage and guide the oncology community to deploy standardized quantitative imaging techniques in clinical trials to further personalize care for cancer patients and to provide a more efficient path for the development of improved targeted therapies. (C) 2016 AACR. C1 [Yankeelov, Thomas E.] Vanderbilt Univ, Dept Radiol, Inst Imaging Sci, Nashville, TN USA. [Yankeelov, Thomas E.] Vanderbilt Univ, Dept Radiol Sci, Nashville, TN USA. [Yankeelov, Thomas E.] Vanderbilt Univ, Dept Biomed Engn, Nashville, TN 37235 USA. [Yankeelov, Thomas E.] Vanderbilt Univ, Dept Phys, Nashville, TN 37235 USA. [Yankeelov, Thomas E.] Vanderbilt Univ, Dept Canc Biol, 221 Kirkland Hall, Nashville, TN 37235 USA. [Mankoff, David A.] Univ Penn, Perelman Sch Med, Radiol Nucl Med, Philadelphia, PA 19104 USA. [Schwartz, Lawrence H.; Zhao, Binsheng] Columbia Univ, Dept Radiol, New York, NY USA. [Lieberman, Frank S.] Univ Pittsburgh, Dept Neurol, Pittsburgh, PA 15260 USA. [Lieberman, Frank S.] Univ Pittsburgh, Dept Neurosurg, Pittsburgh, PA USA. [Lieberman, Frank S.] Univ Pittsburgh, Dept Med Oncol, Pittsburgh, PA USA. [Buatti, John M.] Univ Iowa, Dept Radiat Oncol, Iowa City, IA USA. [Buatti, John M.] Univ Iowa, Dept Otolaryngol, Iowa City, IA USA. [Buatti, John M.] Univ Iowa, Dept Neurosurg, Iowa City, IA USA. [Mountz, James M.] Univ Pittsburgh, Dept Radiol, Div Nucl Med, Pittsburgh, PA 15260 USA. [Erickson, Bradley J.] Mayo Clin, Dept Radiol, Rochester, MN USA. [Fennessy, Fiona M. M.] Brigham & Womens Hosp, Dept Radiol, 75 Francis St, Boston, MA 02115 USA. [Huang, Wei] Oregon Hlth & Sci Univ, Adv Imaging Res Ctr, Portland, OR 97201 USA. [Kalpathy-Cramer, Jayashree] Harvard Univ, Massachusetts Gen Hosp, Dept Radiol, Athinoula A Martinos Ctr Biomed Imaging,Sch Med, Boston, MA USA. [Wahl, Richard L.] Johns Hopkins Univ, Sch Med, Dept Radiol, Baltimore, MD 21205 USA. [Linden, Hannah M.] Univ Washington, Dept Med, Seattle, WA USA. [Kinahan, Paul E.] Univ Washington, Dept Radiol, Seattle, WA 98195 USA. [Hylton, Nola M.] Univ Calif San Francisco, Dept Radiol, San Francisco, CA USA. [Gillies, Robert J.] H Lee Moffitt Canc Ctr & Res Inst, Dept Radiol, Tampa Bay, FL USA. [Clarke, Laurence; Nordstrom, Robert] NCI, Canc Imaging Program, Bethesda, MD 20892 USA. [Rubin, Daniel L.] Stanford Univ, Dept Radiol & Med, Palo Alto, CA 94304 USA. RP Yankeelov, TE (reprint author), Univ Texas Austin, Dept Biomed Engn, 107 W Dean Keeton St,Stop C0800, Austin, TX 78712 USA. EM thomas.yankeelov@utexas.edu FU NIH [U01CA142565, U01CA190254, U01CA140207, U01CA140230, U01CA140206, U01CA160045, U01CA151261, U01CA154602, U01CA154601, U01CA140204, U01CA148131, U01CA151235, U01CA143062, U01CA142555] FX This work was supported by the NIH under award numbers U01CA142565 (to T.E. Yankeelov), U01CA190254 (to D.A. Mankoff), U01CA140207 (to L.H. Schwartz), U01CA140230 (to F.S. Lieberman and J.M. Mountz), U01CA140206 (to J.M. Buatti), U01CA160045 (to B.J. Erickson), U01CA151261 (to F.M.M. Fennessy), U01CA154602 (to W. Huang), U01CA154601 (to J. Kalpathy-Cramer), U01CA140204 (to R.L. Wahl), U01CA148131 (to H.M. Linden and P. Kinahan), U01CA151235 (to N.M. Hylton), U01CA143062 (to R.J. Gillies), and U01CA142555 (to D.L. Rubin). NR 31 TC 7 Z9 7 U1 1 U2 7 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1078-0432 EI 1557-3265 J9 CLIN CANCER RES JI Clin. Cancer Res. PD JAN 15 PY 2016 VL 22 IS 2 BP 284 EP 290 DI 10.1158/1078-0432.CCR-14-3336 PG 7 WC Oncology SC Oncology GA DC2VP UT WOS:000369076500004 PM 26773162 ER PT J AU Kreitman, RJ Stetler-Stevenson, M Jaffe, ES Conlon, KC Steinberg, SM Wilson, W Waldmann, TA Pastan, I AF Kreitman, Robert J. Stetler-Stevenson, Maryalice Jaffe, Elaine S. Conlon, Kevin C. Steinberg, Seth M. Wilson, Wyndham Waldmann, Thomas A. Pastan, Ira TI Complete Remissions of Adult T-cell Leukemia with Anti-CD25 Recombinant Immunotoxin LMB-2 and Chemotherapy to Block Immunogenicity SO CLINICAL CANCER RESEARCH LA English DT Article ID VIRUS TYPE-I; ANTI-TAC; PSEUDOMONAS EXOTOXIN; PHASE-I; MONOCLONAL-ANTIBODY; DENILEUKIN DIFTITOX; LYMPHOMA VIRUS; LEUKEMIA/LYMPHOMA; RECEPTOR; LYMPHOCYTES AB Purpose: Adult T-cell leukemia (ATL) is usually CD25(+) and rapidly fatal. Anti-CD25 recombinant immunotoxin LMB-2 had phase I activity limited by immunogenicity and rapid growth. To prevent antidrug antibodies and leukemic progression between cycles, a phase II trial was performed with LMB-2 after cyclophosphamide and fludarabine. Experimental Design: ATL patients received cyclophosphamide and fludarabine days 1 to 3 and 2 weeks later began up to 6 cycles at 3-week intervals of cyclophosphamide and fludarabine days 1 to 3 followed by LMB-2 30-40 mg/kg i.v. days 3, 5, and 7. Three different dose levels of cyclophosphamide and fludarabine were used, 20+200 (n = 3), 25+250 (n = 12), and 30+300 mg/m(2) (n = 2). Results: Of 17 patients enrolled and treated with fludarabine and cyclophosphamide for cycle-1, 15 received subsequent cycle (s) containing LMB-2 and were therefore evaluable for response. Lack of antibody formation permitted retreatment in most patients. Of 10 evaluable leukemic patients receiving 25+250 or 30+300 mg/m(2) of fludarabine and cyclophosphamide, 6 (60%) achieved complete remission (CR) and 2 (20%) partial remission (PR), and all 5 with >25% leukemic cells achieved CR. No responses were achieved in 5 with lymphomatous ATL or lower fludarabine and cyclophosphamide doses. Median CR duration for the 6 CRs was 40 weeks. One is without detectable ATL at 47 months. Toxicity was mostly attributable to fludarabine and cyclophosphamide. Capillary leak from LMB-2 was non-dose limiting. One patient in CR died of a preexisting infection. Conclusions: LMB-2, administered with fludarabine and cyclophosphamide to prevent antidrug antibodies and rapid intercycle progression, is highly effective in achieving CR in leukemia ATL. Fludarabine and cyclophosphamide dose/schedule is important for safety and efficacy in this high-risk population. (C)2015 AACR. C1 [Kreitman, Robert J.; Pastan, Ira] NCI, Mol Biol Lab, NIH, Bldg 37, Bethesda, MD 20892 USA. [Stetler-Stevenson, Maryalice; Jaffe, Elaine S.] NCI, Pathol Lab, NIH, Bldg 10, Bethesda, MD 20892 USA. [Conlon, Kevin C.; Wilson, Wyndham; Waldmann, Thomas A.] NCI, Lymphoid Malignancies Branch, NIH, Bethesda, MD 20892 USA. [Steinberg, Seth M.] NCI, Biostat & Data Management Sect, Off Clin Director, Ctr Canc Res,NIH, Bethesda, MD 20892 USA. RP Kreitman, RJ (reprint author), NCI, NIH, 9000 Rockville Pike,Bldg 37,Room 5124b, Bethesda, MD 20892 USA. EM kreitmar@mail.nih.gov FU NIH, NCI; Cancer Therapy Evaluation Program, NCI FX This work was supported by the intramural research program, NIH, NCI. The trial was sponsored by the Cancer Therapy Evaluation Program, NCI. NR 42 TC 4 Z9 4 U1 1 U2 5 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1078-0432 EI 1557-3265 J9 CLIN CANCER RES JI Clin. Cancer Res. PD JAN 15 PY 2016 VL 22 IS 2 BP 310 EP 318 DI 10.1158/1078-0432.CCR-15-1412 PG 9 WC Oncology SC Oncology GA DC2VP UT WOS:000369076500007 PM 26350263 ER PT J AU Janovska, P Poppova, L Plevova, K Plesingerova, H Behal, M Kaucka, M Ovesna, P Hlozkova, M Borsky, M Stehlikova, O Brychtova, Y Doubek, M Machalova, M Baskar, S Kozubik, A Pospisilova, S Pavlova, S Bryja, V AF Janovska, Pavlina Poppova, Lucie Plevova, Karla Plesingerova, Hana Behal, Martin Kaucka, Marketa Ovesna, Petra Hlozkova, Michaela Borsky, Marek Stehlikova, Olga Brychtova, Yvona Doubek, Michael Machalova, Michaela Baskar, Sivasubramanian Kozubik, Alois Pospisilova, Sarka Pavlova, Sarka Bryja, Vitezslav TI Autocrine Signaling by Wnt-5a Deregulates Chemotaxis of Leukemic Cells and Predicts Clinical Outcome in Chronic Lymphocytic Leukemia SO CLINICAL CANCER RESEARCH LA English DT Article ID RECEPTOR TYROSINE KINASE; CD38 EXPRESSION; MUTATION STATUS; CLL CELLS; IN-VIVO; B-CELLS; ROR1; SURVIVAL; PATHWAY; CATENIN AB Purpose: ROR1, a receptor in the noncanonical Wnt/planar cell polarity (PCP) pathway, is upregulated in malignant B cells of chronic lymphocytic leukemia (CLL) patients. It has been shown that the Wnt/PCP pathway drives pathogenesis of CLL, but which factors activate the ROR1 and PCP pathway in CLL cells remains unclear. Experimental Design: B lymphocytes from the peripheral blood of CLL patients were negatively separated using RosetteSep (StemCell) and gradient density centrifugation. Relative expression of WNT5A, WNT5B, and ROR1 was assessed by quantitative real-time PCR. Protein levels, protein interaction, and downstream signaling were analyzed by immunoprecipitation and Western blotting. Migration capacity of primary CLL cells was analyzed by the Transwell migration assay. Results: By analyzing the expression in 137 previously untreated CLL patients, we demonstrate that WNT5A and WNT5B genes show dramatically (five orders of magnitude) varying expression in CLL cells. High WNT5A and WNT5B expression strongly associates with unmutated IGHV and shortened time to first treatment. In addition, WNT5A levels associate, independent of IGHV status, with the clinically worst CLL subgroups characterized by dysfunctional p53 and mutated SF3B1. We provide functional evidence that WNT5A-positive primary CLL cells have increased motility and attenuated chemotaxis toward CXCL12 and CCL19 that can be overcome by inhibitors of Wnt/PCP signaling. Conclusions: These observations identify Wnt-5a as the crucial regulator of ROR1 activity in CLL and suggest that the autocrine Wnt-5a signaling pathway allows CLL cells to overcome natural microenvironmental regulation. (C) 2015 AACR. C1 [Janovska, Pavlina; Behal, Martin; Kaucka, Marketa; Kozubik, Alois; Bryja, Vitezslav] Masaryk Univ, Fac Sci, Inst Expt Biol, Kotlarska 2, CS-61137 Brno, Czech Republic. [Poppova, Lucie; Plevova, Karla; Plesingerova, Hana; Borsky, Marek; Stehlikova, Olga; Brychtova, Yvona; Doubek, Michael; Pospisilova, Sarka; Pavlova, Sarka] Univ Hosp Brno, Dept Internal Med Hematol & Oncol, Ctr Mol Biol & Gene Therapy, Brno, Czech Republic. [Poppova, Lucie; Plevova, Karla; Plesingerova, Hana; Borsky, Marek; Stehlikova, Olga; Brychtova, Yvona; Doubek, Michael; Machalova, Michaela; Pospisilova, Sarka; Pavlova, Sarka] Masaryk Univ, Fac Med, Brno, Czech Republic. [Poppova, Lucie; Plevova, Karla; Plesingerova, Hana; Hlozkova, Michaela; Doubek, Michael; Pospisilova, Sarka; Pavlova, Sarka] Masaryk Univ, CEITEC Cent European Inst Technol, Brno, Czech Republic. [Ovesna, Petra] Masaryk Univ, Inst Biostat & Anal, Brno, Czech Republic. [Machalova, Michaela] Univ Hosp Brno, Dept Paediat Otorhinolaryngol, Brno, Czech Republic. [Baskar, Sivasubramanian] NCI, Genet Branch, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. [Kozubik, Alois; Bryja, Vitezslav] Acad Sci Czech Republic, Inst Biophys, Dept Cytokinet, Kralovopolska 135, CS-61265 Brno, Czech Republic. [Kaucka, Marketa] Karolinska Inst, Dept Physiol & Pharmacol, Stockholm, Sweden. RP Bryja, V (reprint author), Masaryk Univ, Fac Sci, Inst Expt Biol, Kotlarska 2, CS-61137 Brno, Czech Republic. EM bryja@sci.muni.cz RI Plesingerova, Hana/E-1076-2012; Bryja, Vit?zslav/H-1925-2014; Pavlova, Sarka/D-2139-2011; OI Plesingerova, Hana/0000-0001-6588-8707; Bryja, Vit?zslav/0000-0002-9136-5085; Kaucka, Marketa/0000-0002-8781-9769 FU Czech Science Foundation [301/11/0747]; Masaryk University Student Grant for Specific Research [MUNI/A/1180/2014, MUNI/A/1398/2014]; Ministry of Health of the Czech Republic [NT11217-5/2010, NT13493-4/2012, 15-29793A]; Ministry of Education, Youth and Sports of the Czech Republic Developmental Fund project [CZ.1.05/1.1.00/02.0068]; Faculty Hospital Brno [FNBr65269705]; Intramural Research Program of the Center for Cancer Research, National Cancer Institute, NIH FX This work was supported by grants from the Czech Science Foundation (301/11/0747), Masaryk University Student Grant for Specific Research MUNI/A/1180/2014 and MUNI/A/1398/2014, Ministry of Health of the Czech Republic (NT11217-5/2010, NT13493-4/2012, 15-29793A), Ministry of Education, Youth and Sports of the Czech Republic Developmental Fund project CZ.1.05/1.1.00/02.0068 (CEITEC), and Faculty Hospital Brno (FNBr65269705). This work was supported in part by the Intramural Research Program of the Center for Cancer Research, National Cancer Institute, NIH (SB). NR 35 TC 3 Z9 3 U1 5 U2 11 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1078-0432 EI 1557-3265 J9 CLIN CANCER RES JI Clin. Cancer Res. PD JAN 15 PY 2016 VL 22 IS 2 BP 459 EP 469 DI 10.1158/1078-0432.CCR-15-0154 PG 11 WC Oncology SC Oncology GA DC2VP UT WOS:000369076500022 PM 26240275 ER PT J AU Starnes, LM Su, D Pikkupeura, LM Weinert, BT Santos, MA Mund, A Soria, R Cho, YW Pozdnyakova, I Hojfeldt, MK Vala, A Yang, WJ Lopez-Mendez, B Lee, JE Peng, WQ Yuan, J Ge, K Montoya, G Nussenzweig, A Choudhary, C Daniel, JA AF Starnes, Linda M. Su, Dan Pikkupeura, Laura M. Weinert, Brian T. Santos, Margarida A. Mund, Andreas Soria, Rebeca Cho, Young-Wook Pozdnyakova, Irina Hojfeldt, Martina Kubec Vala, Andrea Yang, Wenjing Lopez-Mendez, Blanca Lee, Ji-Eun Peng, Weiqun Yuan, Joan Ge, Kai Montoya, Guillermo Nussenzweig, Andre Choudhary, Chunaram Daniel, Jeremy A. TI A PTIP-PA1 subcomplex promotes transcription for IgH class switching independently from the associated MLL3/MLL4 methyltransferase complex SO GENES & DEVELOPMENT LA English DT Article DE histone methylation; BRCT domains; DNA damage; antigen receptor rearrangements; 53BP1; PTIP ID DNA-DAMAGE-RESPONSE; B-CELL LYMPHOMA; BRCT-DOMAIN; RECOMBINATION; 53BP1; EXPRESSION; BINDING; REPAIR; CHROMATIN; QUANTIFICATION AB Class switch recombination (CSR) diversifies antibodies for productive immune responses while maintaining stability of the B-cell genome. Transcription at the immunoglobulin heavy chain (Igh) locus targets CSR-associated DNA damage and is promoted by the BRCT domain-containing PTIP (Pax transactivation domain-interacting protein). Although PTIP is a unique component of the mixed-lineage leukemia 3 (MLL3)/MLL4 chromatin-modifying complex, the mechanisms for how PTIP promotes transcription remain unclear. Here we dissected the minimal structural requirements of PTIP and its different protein complexes using quantitative proteomics in primary lymphocytes. We found that PTIP functions in transcription and CSR separately from its association with the MLL3/MLL4 complex and from its localization to sites of DNA damage. We identified a tandem BRCT domain of PTIP that is sufficient for CSR and identified PA1 as its main functional protein partner. Collectively, we provide genetic and biochemical evidence that a PTIP PA1 subcomplex functions independently from the MLL3/MLL4 complex to mediate transcription during CSR. These results further our understanding of how multifunctional chromatin-modifying complexes are organized by subcomplexes that harbor unique and distinct activities. C1 [Starnes, Linda M.; Su, Dan; Pikkupeura, Laura M.; Mund, Andreas; Soria, Rebeca; Hojfeldt, Martina Kubec; Daniel, Jeremy A.] Univ Copenhagen, Fac Hlth & Med Sci, Novo Nordisk Fdn, Ctr Prot Res,Chromatin Struct & Funct Grp, DK-2200 Copenhagen, Denmark. [Weinert, Brian T.; Choudhary, Chunaram] Univ Copenhagen, Fac Hlth & Med Sci, Novo Nordisk Fdn, Prote & Cell Signaling Grp,Ctr Prot Res, DK-2200 Copenhagen, Denmark. [Santos, Margarida A.; Nussenzweig, Andre] NCI, Lab Genome Integr, NIH, Bethesda, MD 20892 USA. [Cho, Young-Wook; Lee, Ji-Eun; Ge, Kai] NIDDK, Adipocyte Biol & Gene Regulat Sect, Lab Endocrinol & Receptor Biol, NIH, Bethesda, MD 20892 USA. [Pozdnyakova, Irina; Vala, Andrea; Lopez-Mendez, Blanca; Montoya, Guillermo] Univ Copenhagen, Fac Hlth & Med Sci, Novo Nordisk Fdn, Ctr Prot Res,Protein Prod & Characterizat Platfor, DK-2200 Copenhagen, Denmark. [Yang, Wenjing; Peng, Weiqun] George Washington Univ, Dept Phys, Washington, DC 20052 USA. [Yuan, Joan] Lund Univ, Fac Med, Lund Stem Cell Ctr, Dev Immunol Grp,Div Mol Hematol, S-22184 Lund, Sweden. [Montoya, Guillermo] Univ Copenhagen, Fac Hlth & Med Sci, Novo Nordisk Fdn, Ctr Prot Res,Macromol Crystallog Grp, DK-2200 Copenhagen, Denmark. RP Daniel, JA (reprint author), Univ Copenhagen, Fac Hlth & Med Sci, Novo Nordisk Fdn, Ctr Prot Res,Chromatin Struct & Funct Grp, DK-2200 Copenhagen, Denmark. EM jeremy.daniel@cpr.ku.dk RI yuan, joan/A-8185-2013; Daniel, Jeremy/S-4729-2016 OI yuan, joan/0000-0001-9129-8356; Daniel, Jeremy/0000-0002-1981-5571 FU Danish Council for Independent Research in Medical Sciences; Danish Cancer Society; Center for Protein Research from the Novo Nordisk Foundation [NNF14CC0001]; National Institute of Allergy and Infectious Diseases of the National Institutes of Health [R21AI113806]; International Masters Scholarship from the Lundbeck Foundation; Marie Curie Intra-European Fellowship for Career Development [627187] FX We thank Jutta Bulkescher for technical assistance with imaging; Gelo Dela Cruz (DanStem) for FACS sorting; Davide Robbiani for helpful advice and constructs regarding cloning of the PTIP-GFP knock-in vector; Jae W. Lee for the MLL3flox/flox mice; Gustavo Gutierrez-Cruz for technical assistance with ChIP-seq; Tobias Gustaysson, Khalid Pardes, and Mia Nielsen for recombinant protein expression and purification; and Javier Gonzalez (University of Copenhagen Core Facility for Transgenic Mice) for technical assistance with electroporation of embryonic stem cells and blastocyst injections. We also thank Jiri Lukas, Andres Lopez-Contreras, and Valentyn Oksenych for critical reading of the manuscript. This work was supported by the Danish Council for Independent Research in Medical Sciences with a Sapere Aude Starting Grant to J.A.D. and a post-doctoral Fellowship to L.M.S. The Daniel laboratory was also supported by the Danish Cancer Society and a grant to the Center for Protein Research from the Novo Nordisk Foundation (NNF14CC0001). The work in the Choudhary laboratory was supported by the Danish Council for Independent Research in Medical Sciences with a Sapere Aude Starting Grant. The work in the Peng laboratory was supported by the National Institute of Allergy and Infectious Diseases of the National Institutes of Health (award R21AI113806). L.M.P. is supported by an International Masters Scholarship from the Lundbeck Foundation. A.M. is supported by a Marie Curie Intra-European Fellowship for Career Development (project no. 627187). NR 52 TC 1 Z9 1 U1 1 U2 3 PU COLD SPRING HARBOR LAB PRESS, PUBLICATIONS DEPT PI COLD SPRING HARBOR PA 1 BUNGTOWN RD, COLD SPRING HARBOR, NY 11724 USA SN 0890-9369 EI 1549-5477 J9 GENE DEV JI Genes Dev. PD JAN 15 PY 2016 VL 30 IS 2 BP 149 EP 163 DI 10.1101/gad.268797.115 PG 15 WC Cell Biology; Developmental Biology; Genetics & Heredity SC Cell Biology; Developmental Biology; Genetics & Heredity GA DC3NA UT WOS:000369124800002 PM 26744420 ER PT J AU van Baars, R van der Marel, J Snijders, PJF Rodriquez-Manfredi, A ter Harmsel, B van den Munckhof, HAM Ordi, J del Pino, M van de Sandt, MM Wentzensen, N Meijer, CJLM Quint, WGV AF van Baars, Romy van der Marel, Jacolien Snijders, Peter J. F. Rodriquez-Manfredi, Agata ter Harmsel, Bram van den Munckhof, Henk A. M. Ordi, Jaume del Pino, Marta van de Sandt, Miekel M. Wentzensen, N. Meijer, Chris J. L. M. Quint, Wim G. V. TI CADM1 and MAL methylation status in cervical scrapes is representative of the most severe underlying lesion in women with multiple cervical biopsies SO INTERNATIONAL JOURNAL OF CANCER LA English DT Article DE DNA methylation; tumour suppressor genes; human papillomavirus; cervical intraepithelial neoplasia; cervical cancer ID HUMAN-PAPILLOMAVIRUS; INTRAEPITHELIAL NEOPLASIA; DNA METHYLATION; PROMOTER HYPERMETHYLATION; NATURAL-HISTORY; INVASIVE CANCER; PCR ASSAY; TIME; RISK; INFECTIONS AB Recent studies have shown that CADM1/MAL methylation levels in cervical scrapes increase with severity and duration of the underlying cervical intraepithelial neoplasia (CIN) lesion. Multiple lesions of different histological grades and duration are frequently present on the cervix. To gain more insight into the possible epigenetic heterogeneity and its consequences for the methylation status in cervical scrapes, we performed an exploratory study of CADM1/MAL methylation in different grades of CIN lesions present in women with multiple cervical biopsies. CADM1-M18 and MAL-M1 methylation was assessed using a standardised, multiplex, quantitative methylation specific PCR on 178 biopsies with various grades of CIN in 65 women, and in their corresponding cervical scrapes. CADM1/MAL methylation positivity increased with disease severity, from 5.5% in normal biopsies to 63.3% and 100% in biopsies with CIN3 and cervical cancer, respectively. In the majority (8/9) of women where besides a CIN2/3 lesion a biopsy from normal cervical tissue was present, the CIN2/3 biopsy was CADM1/MAL methylation positive and the normal biopsy was CADM1/MAL methylation negative. A good concordance (78%) was found between CADM1/MAL methylation results on the scrapes and the biopsy with the worst diagnosis, particularly between samples of women with CIN3 and cervical cancer (92% and 100% concordance, respectively). Thus, in women with multiple cervical biopsies, CADM1/MAL methylation increases with severity of the lesion and is lesion-specific. CADM1/MAL methylation status in cervical scrapes appears to be representative of the worst underlying lesion, particularly for CIN3 and cervical cancer. C1 [van Baars, Romy; van der Marel, Jacolien; van den Munckhof, Henk A. M.; van de Sandt, Miekel M.; Quint, Wim G. V.] DDL Diagnost Lab, Visseringlaan 25, NL-2288 ER Rijswijk, Netherlands. [Snijders, Peter J. F.; Meijer, Chris J. L. M.] Vrije Univ Amsterdam Med Ctr, Dept Pathol, Amsterdam, Netherlands. [Rodriquez-Manfredi, Agata; del Pino, Marta] Hosp Clin Barcelona, Dept Obstet & Gynaecol, Barcelona, Spain. [ter Harmsel, Bram] Roosevelt Klin, Leiden, Netherlands. [Ordi, Jaume] Univ Barcelona, Fac Med, Hosp Clin, CRESIB,Dept Pathol, Barcelona 7, Spain. [Wentzensen, N.] NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. RP Quint, WGV (reprint author), DDL Diagnost Lab, Visseringlaan 25, NL-2288 ER Rijswijk, Netherlands. EM wim.quint@ddl.nl FU Stichting Pathologie Ontwikkeling en Onderzoek (SPOO) Foundation, The Netherlands; Instituto de Salud Carlos III (ICSIII)-Fondos de Investigacion Sanitaria; ERDF "one way to Europe" [PI12/01165, PI12/01231] FX Grant sponsors: Stichting Pathologie Ontwikkeling en Onderzoek (SPOO) Foundation, The Netherlands and Instituto de Salud Carlos III (ICSIII)-Fondos de Investigacion Sanitaria, and ERDF "one way to Europe;"; Grant numbers: PI12/01165 and PI12/01231 NR 40 TC 2 Z9 2 U1 1 U2 2 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0020-7136 EI 1097-0215 J9 INT J CANCER JI Int. J. Cancer PD JAN 15 PY 2016 VL 138 IS 2 BP 463 EP 471 DI 10.1002/ijc.29706 PG 9 WC Oncology SC Oncology GA DC4AF UT WOS:000369161200021 PM 26219541 ER PT J AU Domingo-Gonzalez, R Martinez-Colon, GJ Smith, AJ Smith, CK Ballinger, MN Xia, M Murray, S Kaplan, MJ Yanik, GA Moore, BB AF Domingo-Gonzalez, Racquel Martinez-Colon, Giovanny J. Smith, Alana J. Smith, Carolyne K. Ballinger, Megan N. Xia, Meng Murray, Susan Kaplan, Mariana J. Yanik, Gregory A. Moore, Bethany B. TI Inhibition of Neutrophil Extracellular Trap Formation after Stem Cell Transplant by Prostaglandin E-2 SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Article DE granulocyte; transplant; NETosis; prostaglandin; bacteria ID BONE-MARROW-TRANSPLANTATION; PROTEIN-KINASE-A; PULMONARY COMPLICATIONS; PSEUDOMONAS-AERUGINOSA; STAPHYLOCOCCUS-AUREUS; CYCLIC-AMP; PHAGOCYTOSIS; DISEASE; AUTOPHAGY; IMMUNITY AB Rationale: Autologous and allogeneic hematopoietic stem cell transplant (HSCT) patients are susceptible to pulmonary infections, including bacterial pathogens, even after hematopoietic reconstitution. We previously reported that murine bone marrow transplant (BMT) neutrophils overexpress cydooxygenase-2, overproduce prostaglandin E-2 (PGE(2)), and exhibit defective intracellular bacterial killing. Neutrophil extracellular traps (NETs) are DNA structures that capture and kill extracellular bacteria and other pathogens. Objectives: To determine whether NETosis was defective after transplant and if so, whether this was regulated by PGE(2) signaling. Methods: Neutrophils isolated from mice and humans (both control and HSCT subjects) were analyzed for NETosis in response to various stimuli in the presence or absence of PGE(2) signaling modifiers. Measurements and Main Results: NETs were visualized by immunofluorescence or quantified by Sytox Green fluorescence. Treatment of BMT or HSCT neutrophils with phorbol 12-myristate 13-acetate or rapamycin resulted in reduced NET formation relative to control cells. NET formation after BMT was rescued both in vitro and in vivo with cydoox-ygenase inhibitors. Additionally, the EP2 receptor antagonist (PP-04418948) or the EP4 antagonist (AE3-208) restored NET formation in neutrophils isolated from BMT mice or HSCT patients. Exogenous PGE(2) treatment limited NETosis of neutrophils collected from normal human volunteers and naive mice in an exchange protein activated by cAMP- and protein kinase A-dependent manner. Conclusions: Our results suggest blockade of the PGE(2)-EP2 or EP4 signaling pathway restores NETosis after transplantation. Furthermore, these data provide the first description of a physiologic inhibitor of NETosis. C1 [Domingo-Gonzalez, Racquel; Martinez-Colon, Giovanny J.; Smith, Carolyne K.] Univ Michigan, Sch Publ Hlth, Immunol Grad Program, Ann Arbor, MI 48109 USA. [Smith, Alana J.] Univ Michigan, Sch Publ Hlth, Summer Undergrad Res Program, Ann Arbor, MI 48109 USA. [Xia, Meng; Murray, Susan] Univ Michigan, Sch Publ Hlth, Biostat Dept, Ann Arbor, MI 48109 USA. [Yanik, Gregory A.] Univ Michigan, Sch Med, Div Hematol Oncol, Dept Pediat, Ann Arbor, MI USA. [Moore, Bethany B.] Univ Michigan, Dept Internal Med, Pulm & Crit Care Med Div, Ann Arbor, MI 48109 USA. [Moore, Bethany B.] Univ Michigan, Dept Microbiol & Immunol, Ann Arbor, MI 48109 USA. [Smith, Carolyne K.; Kaplan, Mariana J.] NIAMSD, System Autoimmun Branch, NIH, Bethesda, MD 20892 USA. [Ballinger, Megan N.] Ohio State Univ, Dept Internal Med, Pulmonary Allergy Crit Care & Sleep Div, Columbus, OH 43210 USA. RP Moore, BB (reprint author), 4053 BSRB,109 Zina Pitcher Pl, Ann Arbor, MI 48103 USA. EM bmoore@umich.edu OI Murray, Susan/0000-0003-4387-7673; Moore, Bethany/0000-0003-3051-745X FU National Institutes of Health [R56AI065543, AI117229, HL115618]; Michigan CTSA [UL1TR000433, T32AI007413]; American Heart Association; Miller Fund Award for Innovative Immunology Research FX Supported by National Institutes of Health grants R56AI065543, AI117229, and HL115618 (B.B.M.); a pilot grant from the Michigan CTSA (UL1TR000433), T32AI007413 (R.D.-G. and G.J.M-.C.); an award from the American Heart Association (R.D.-G.); and the Miller Fund Award for Innovative Immunology Research (R.D.-G.). NR 53 TC 7 Z9 7 U1 4 U2 5 PU AMER THORACIC SOC PI NEW YORK PA 25 BROADWAY, 18 FL, NEW YORK, NY 10004 USA SN 1073-449X EI 1535-4970 J9 AM J RESP CRIT CARE JI Am. J. Respir. Crit. Care Med. PD JAN 15 PY 2016 VL 193 IS 2 BP 186 EP 197 DI 10.1164/rccm.201501-0161OC PG 12 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA DB3AK UT WOS:000368381700013 PM 26417909 ER PT J AU Bonesso, MF Yeh, AJ Villaruz, AE Joo, HS McCausland, J Fortaleza, CMCB Cavalcante, RS Sobrinho, MT Ronchi, CF Cheung, GYC Cunha, MLRS Otto, M AF Bonesso, Mariana F. Yeh, Anthony J. Villaruz, Amer E. Joo, Hwang-Soo McCausland, Joshua Fortaleza, Carlos M. C. B. Cavalcante, Ricardo S. Sobrinho, Moises T. Ronchi, Carlos F. Cheung, Gordon Y. C. Cunha, Maria L. R. S. Otto, Michael TI Key Role of alpha-Toxin in Fatal Pneumonia Caused by Staphylococcus aureus Sequence Type 398 SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Letter ID VIRULENCE C1 [Bonesso, Mariana F.; Yeh, Anthony J.; Villaruz, Amer E.; Joo, Hwang-Soo; McCausland, Joshua; Cheung, Gordon Y. C.; Otto, Michael] NIH, Bethesda, MD 20892 USA. [Bonesso, Mariana F.; Fortaleza, Carlos M. C. B.; Cavalcante, Ricardo S.; Sobrinho, Moises T.; Ronchi, Carlos F.; Cunha, Maria L. R. S.] Univ Estadual Paulista, Botucatu, SP, Brazil. RP Bonesso, MF (reprint author), NIH, Bldg 10, Bethesda, MD 20892 USA. RI Fortaleza, Carlos Magno/C-3807-2013 OI Fortaleza, Carlos Magno/0000-0003-4120-1258 FU Intramural NIH HHS; NIAID NIH HHS [ZIA AI000904] NR 10 TC 1 Z9 1 U1 0 U2 2 PU AMER THORACIC SOC PI NEW YORK PA 25 BROADWAY, 18 FL, NEW YORK, NY 10004 USA SN 1073-449X EI 1535-4970 J9 AM J RESP CRIT CARE JI Am. J. Respir. Crit. Care Med. PD JAN 15 PY 2016 VL 193 IS 2 BP 217 EP 220 PG 4 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA DB3AK UT WOS:000368381700020 PM 26771417 ER PT J AU Lastwika, KJ Wilson, W Li, QK Norris, J Xu, HY Ghazarian, SR Kitagawa, H Kawabata, S Taube, JM Yao, S Liu, LN Gills, JJ Dennis, PA AF Lastwika, Kristin J. Wilson, Willie, III Li, Qing Kay Norris, Jeffrey Xu, Haiying Ghazarian, Sharon R. Kitagawa, Hiroshi Kawabata, Shigeru Taube, Janis M. Yao, Sheng Liu, Linda N. Gills, Joell J. Dennis, Phillip A. TI Control of PD-L1 Expression by Oncogenic Activation of the AKT-mTOR Pathway in Non-Small Cell Lung Cancer SO CANCER RESEARCH LA English DT Article ID K-RAS; T-CELLS; ANTI-PD-L1 ANTIBODY; LIGAND-1 EXPRESSION; B7-H1 EXPRESSION; GENE-EXPRESSION; UP-REGULATION; PHASE-I; KINASE; TUMORIGENESIS AB Alterations in EGFR, KRAS, and ALK are oncogenic drivers in lung cancer, but how oncogenic signaling influences immunity in the tumor microenvironment is just beginning to be understood. Immunosuppression likely contributes to lung cancer, because drugs that inhibit immune checkpoints like PD-1 and PD-L1 have clinical benefit. Here, we show that activation of the AKT-mTOR pathway tightly regulates PD-L1 expression in vitro and in vivo. Both oncogenic and IFNg-mediated induction of PD-L1 was dependent on mTOR. In human lung adenocarcinomas and squamous cell carcinomas, membranous expression of PD-L1 was significantly associated with mTOR activation. These data suggest that oncogenic activation of the AKT-mTOR pathway promotes immune escape by driving expression of PD-L1, which was confirmed in syngeneic and genetically engineered mouse models of lung cancer where anmTOR inhibitor combined with a PD-1 antibody decreased tumor growth, increased tumor-infiltrating T cells, and decreased regulatory T cells. (C) 2015 AACR. C1 [Lastwika, Kristin J.; Norris, Jeffrey; Kitagawa, Hiroshi; Kawabata, Shigeru; Gills, Joell J.; Dennis, Phillip A.] Johns Hopkins Univ, Dept Oncol, Baltimore, MD USA. [Lastwika, Kristin J.] George Washington Univ, Inst Biomed Sci, Washington, DC USA. [Wilson, Willie, III] NIH, Canc Biol & Genet Branch, Ctr Canc Res, Bldg 10, Bethesda, MD 20892 USA. [Li, Qing Kay] Johns Hopkins Univ, Dept Pathol, Baltimore, MD USA. [Xu, Haiying; Taube, Janis M.] Johns Hopkins Univ, Dept Dermatol, Baltimore, MD 21218 USA. [Ghazarian, Sharon R.] Johns Hopkins Univ, Biostat Epidemiol & Data Management Core, Baltimore, MD USA. [Yao, Sheng; Liu, Linda N.] Amplimmune Inc, Gaithersburg, MD USA. RP Dennis, PA (reprint author), Johns Hopkins Univ, Sch Med, 4940 Eastern Ave,301 Bldg Suite 4500, Baltimore, MD 21224 USA. EM pdennis@jhmi.edu FU National Cancer Institute; George Washington University; NIH [P30 CA006973] FX This work was supported by intramural funding from the National Cancer Institute, the George Washington University, and NIH grant P30 CA006973. NR 51 TC 23 Z9 24 U1 11 U2 23 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 JAN 15 PY 2016 VL 76 IS 2 BP 227 EP 238 DI 10.1158/0008-5472.CAN-14-3362 PG 12 WC Oncology SC Oncology GA DB6MB UT WOS:000368628000008 PM 26637667 ER PT J AU Nagarsheth, N Peng, DJ Kryczek, I Wu, K Li, W Zhao, ED Zhao, LL Wei, S Frankel, T Vatan, L Szeliga, W Dou, YL Owens, S Marquez, V Tao, KX Huang, E Wang, GB Zou, WP AF Nagarsheth, Nisha Peng, Dongjun Kryczek, Ilona Wu, Ke Li, Wei Zhao, Ende Zhao, Lili Wei, Shuang Frankel, Timothy Vatan, Linda Szeliga, Wojciech Dou, Yali Owens, Scott Marquez, Victor Tao, Kaixiong Huang, Emina Wang, Guobin Zou, Weiping TI PRC2 Epigenetically Silences Th1-Type Chemokines to Suppress Effector T-Cell Trafficking in Colon Cancer SO CANCER RESEARCH LA English DT Article ID COLORECTAL-CANCER; IMMUNOTHERAPY; METASTASIS; SURVIVAL; METHYLATION; EXPRESSION; INHIBITOR; BLOCKADE; STEMNESS; IMMUNITY AB Infiltration of tumors with effector T cells is positively associated with therapeutic efficacy and patient survival. However, the mechanisms underlying effector T-cell trafficking to the tumor microenvironment remain poorly understood in patients with colon cancer. The polycomb repressive complex 2 (PRC2) is involved in cancer progression, but the regulation of tumor immunity by epigenetic mechanisms has yet to be investigated. In this study, we examined the relationship between the repressive PRC2 machinery and effector T-cell trafficking. We found that PRC2 components and demethylase JMJD3-mediated histone H3 lysine 27 trimethylation (H3K27me3) repress the expression and subsequent production of Th1-type chemokines CXCL9 and CXCL10, mediators of effector T-cell trafficking. Moreover, the expression levels of PRC2 components, including EZH2, SUZ12, and EED, were inversely associated with those of CD4, CD8, and Th1-type chemokines in human colon cancer tissue, and this expression pattern was significantly associated with patient survival. Collectively, our findings reveal that PRC2-mediated epigenetic silencing is not only a crucial oncogenic mechanism, but also a key circuit controlling tumor immunosuppression. Therefore, targeting epigenetic programs may have significant implications for improving the efficacy of current cancer immunotherapies relying on effective T-cell-mediated immunity at the tumor site. (C) 2015 AACR. C1 [Nagarsheth, Nisha; Peng, Dongjun; Kryczek, Ilona; Li, Wei; Zhao, Ende; Wei, Shuang; Frankel, Timothy; Vatan, Linda; Szeliga, Wojciech; Zou, Weiping] Univ Michigan, Sch Med, Dept Surg, 109 Zina Pitcher Pl, Ann Arbor, MI 48109 USA. [Nagarsheth, Nisha; Kryczek, Ilona; Zou, Weiping] Univ Michigan, Sch Med, Grad Program Immunol, Ann Arbor, MI USA. [Nagarsheth, Nisha; Kryczek, Ilona; Zou, Weiping] Univ Michigan, Sch Med, Grad Program Canc Biol, Ann Arbor, MI USA. [Wu, Ke; Li, Wei; Zhao, Ende; Tao, Kaixiong; Wang, Guobin] Huazhong Univ Sci & Technol, Tongji Med Coll, Union Hosp, Dept Surg, Wuhan 430074, Peoples R China. [Zhao, Lili] Univ Michigan, Dept Biostat, Sch Med, Ann Arbor, MI 48109 USA. [Dou, Yali; Owens, Scott] Univ Michigan, Sch Med, Dept Pathol, Ann Arbor, MI USA. [Marquez, Victor] NCI, Biol Chem Lab, Ctr Canc Res, Frederick, MD 21701 USA. [Huang, Emina] Case Western Reserve Univ, Dept Colorectal Surg, Cleveland, OH 44106 USA. [Huang, Emina] Case Western Reserve Univ, Dept Stem Cell Biol & Regenerat Med, Cleveland, OH 44106 USA. [Zou, Weiping] Univ Michigan, Ctr Comprehens Canc, Sch Med, Ann Arbor, MI USA. RP Zou, WP (reprint author), Univ Michigan, Sch Med, Dept Surg, 109 Zina Pitcher Pl, Ann Arbor, MI 48109 USA. EM wzou@med.umich.edu RI Zhao, Ende/B-9851-2013 FU NIH [CA123088, CA099985, CA156685, CA171306, CA142808, CA157663, F31CA189440]; Chinese Ministry of Science and Technology (973 program) [2015CB554000]; Wuhan Union Hospital Research Fund; Herman and Dorothy Miller Award for Innovative Immunology Research; Intramural Research Program of the NIH; NCI FX This work is supported (in part) by the NIH grants (CA123088, CA099985, CA156685, and CA171306 to W. Zou; CA142808 and CA157663 to E. Huang; F31CA189440 to N. Nagarsheth), the Chinese Ministry of Science and Technology (973 program, 2015CB554000), the Wuhan Union Hospital Research Fund, Herman and Dorothy Miller Award for Innovative Immunology Research, the Intramural Research Program of the NIH, and the NCI. NR 36 TC 11 Z9 11 U1 3 U2 12 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 JAN 15 PY 2016 VL 76 IS 2 BP 275 EP 282 DI 10.1158/0008-5472.CAN-15-1938 PG 8 WC Oncology SC Oncology GA DB6MB UT WOS:000368628000012 PM 26567139 ER PT J AU Racsa, LD Kraft, CS Olinger, GG Hensley, LE AF Racsa, Lori D. Kraft, Colleen S. Olinger, Gene G. Hensley, Lisa E. TI Viral Hemorrhagic Fever Diagnostics SO CLINICAL INFECTIOUS DISEASES LA English DT Article DE viral hemorrhagic fever; diagnostics; Ebola ID MEDIATED ISOTHERMAL AMPLIFICATION; RIFT-VALLEY FEVER; REVERSE TRANSCRIPTION-PCR; EBOLA-VIRUS DISEASE; REAL-TIME PCR; RAPID DETECTION; DENGUE VIRUS; CLINICAL SPECIMENS; FIELD-EVALUATION; SIERRA-LEONE AB There are 4 families of viruses that cause viral hemorrhagic fever (VHF), including Filoviridae. Ebola virus is one virus within the family Filoviridae and the cause of the current outbreak of VHF in West Africa. VHF-endemic areas are found throughout the world, yet traditional diagnosis of VHF has been performed in large reference laboratories centered in Europe and the United States. The large amount of capital needed, as well as highly trained and skilled personnel, has limited the availability of diagnostics in endemic areas except in conjunction with governmental and nongovernmental entities. However, rapid diagnosis of VHF is essential to efforts that will limit outbreaks. In addition, increased global travel suggests VHF diagnoses may be made outside of the endemic areas. Thus, understanding how to diagnose VHF is imperative for laboratories worldwide. This article reviews traditional and current diagnostic modalities for VHF. C1 [Racsa, Lori D.; Kraft, Colleen S.] Emory Univ, Dept Pathol & Lab Med, Atlanta, GA 30322 USA. [Olinger, Gene G.; Hensley, Lisa E.] NIAID, Integrated Res Facil, Div Clin Res, Frederick, MD USA. RP Kraft, CS (reprint author), Emory Univ Hosp, F145C,1364 Clifton Rd NE, Atlanta, GA 30322 USA. EM colleen.kraft@emory.edu NR 54 TC 4 Z9 4 U1 1 U2 29 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 JAN 15 PY 2016 VL 62 IS 2 BP 214 EP 219 DI 10.1093/cid/civ792 PG 6 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA DB6JW UT WOS:000368622300019 PM 26354968 ER PT J AU Korthuis, PT McGinnis, KA Kraemer, KL Gordon, AJ Skanderson, M Justice, AC Crystal, S Goetz, MB Gibert, CL Rimland, D Fiellin, LE Gaither, JR Wang, K Asch, SM McInnes, DK Ohl, ME Bryant, K Tate, JP Duggal, M Fiellin, DA AF Korthuis, Philip Todd McGinnis, Kathleen A. Kraemer, Kevin L. Gordon, Adam J. Skanderson, Melissa Justice, Amy C. Crystal, Stephen Goetz, Matthew Bidwell Gibert, Cynthia L. Rimland, David Fiellin, Lynn E. Gaither, Julie R. Wang, Karen Asch, Steven M. McInnes, Donald Keith Ohl, Michael E. Bryant, Kendall Tate, Janet P. Duggal, Mona Fiellin, David A. CA Veterans Aging Cohort Study TI Quality of HIV Care and Mortality Rates in HIV-Infected Patients SO CLINICAL INFECTIOUS DISEASES LA English DT Article DE alcohol; quality of health care; HIV; health care; opioid-related disorders ID HUMAN-IMMUNODEFICIENCY-VIRUS; VETERANS AGING COHORT; OF-CARE; PERFORMANCE-MEASURES; ANTIRETROVIRAL THERAPY; ALCOHOL-CONSUMPTION; UNHEALTHY ALCOHOL; UNITED-STATES; SYSTEM; TRANSFORMATION AB Background. The Patient Protection and Affordable Care Act encourages healthcare systems to track quality-of-care measures; little is known about their impact on mortality rates. The objective of this study was to assess associations between HIV quality of care and mortality rates. Methods. A longitudinal survival analysis of the Veterans Aging Cohort Study included 3038 human immunodeficiency virus (HIV)-infected patients enrolled between June 2002 and July 2008. The independent variable was receipt of >= 80% of 9 HIV quality indicators (QIs) abstracted from medical records in the 12 months after enrollment. Overall mortality rates through 2014 were assessed from the Veterans Health Administration, Medicare, and Social Security National Death Index records. We assessed associations between receiving >= 80% of HIV QIs and mortality rates using Kaplan-Meier survival analysis and adjusted Cox proportional hazards models. Results were stratified by unhealthy alcohol and illicit drug use. Results. The majority of participants were male (97.5%) and black (66.8%), with a mean (standard deviation) age of 49.0 (8.8) years. Overall, 25.9% reported past-year unhealthy alcohol use and 28.4% reported past-year illicit drug use. During 24 805 person-years of follow-up (mean [standard deviation], 8.2 [3.3] years), those who received >= 80% of QIs experienced lower age-adjusted mortality rates (adjusted hazard ratio, 0.75; 95% confidence interval,.65-.86). Adjustment for disease severity attenuated the association. Conclusions. Receipt of >= 80% of select HIV QIs is associated with improved survival in a sample of predominantly male, black, HIV-infected patients but was insufficient to overcome adjustment for disease severity. Interventions to ensure high-quality care and address underlying chronic illness may improve survival in HIV-infected patients. C1 [Korthuis, Philip Todd] Oregon Hlth & Sci Univ, Portland, OR 97201 USA. [Gordon, Adam J.] Univ Pittsburgh, Ctr Hlth Equity Res & Promot, Pittsburgh, PA 15260 USA. [McGinnis, Kathleen A.; Kraemer, Kevin L.; Skanderson, Melissa] Univ Pittsburgh, VA Pittsburgh Healthcare Syst, Pittsburgh, PA 15260 USA. [Gordon, Adam J.] Univ Pittsburgh, Dept Med, Ctr Res Hlth Care, Div Gen Internal Med, 930 Scaife Hall, Pittsburgh, PA 15260 USA. [Justice, Amy C.; Fiellin, Lynn E.; Wang, Karen; Tate, Janet P.; Fiellin, David A.] Yale Univ, Sch Med, Ctr Interdisciplinary Res AIDS, Div Gen Internal Med, New Haven, CT USA. [Gaither, Julie R.] Yale Univ, Sch Publ Hlth, Dept Epidemiol Microbial Dis, New Haven, CT USA. [Justice, Amy C.; Tate, Janet P.] Vet Aging Cohort Study Coordinating Ctr, West Haven, CT USA. [Duggal, Mona] VA Connecticut Care Syst, West Haven, CT USA. [Crystal, Stephen] Rutgers State Univ, Inst Hlth Hlth Care Policy & Aging Res, 30 Coll Ave, New Brunswick, NJ 08903 USA. [Goetz, Matthew Bidwell] Univ Calif Los Angeles, VA Greater Angeles Healthcare Syst & David Geffen, Los Angeles, CA 90024 USA. [Asch, Steven M.] VA Greater Palo Alto Healthcare Syst, Palo Alto, CA USA. [Asch, Steven M.] Stanford Univ, Stanford, CA 94305 USA. [Gibert, Cynthia L.] VA Med Ctr, Washington, DC USA. [Gibert, Cynthia L.] George Washington Univ, Med Ctr, Washington, DC 20037 USA. [Rimland, David] VA Med Ctr, Atlanta, GA USA. [Rimland, David] Emory Univ, Sch Med, Atlanta, GA 30322 USA. [McInnes, Donald Keith] Boston Univ, Boston, MA 02215 USA. [Ohl, Michael E.] Univ Iowa, Carver Coll Med, Iowa City, IA USA. [Bryant, Kendall] NIAAA, HIV AIDS Res, Rockville, MD 20852 USA. [Duggal, Mona] Postgrad Inst Med Educ & Res, Chandigarh, India. RP Korthuis, PT (reprint author), Oregon Hlth & Sci Univ, 3181 SW Sam Jackson Pk Rd,Mail Code L-475, Portland, OR 97239 USA. EM korthuis@ohsu.edu OI Fiellin, David/0000-0002-4006-010X; Justice, Amy/0000-0003-0139-5502 FU National Institutes of Health (NIH), National Institute on Alcohol Abuse and Alcoholism (NIAAA) [U24-AA020794, NIAAA U01-AA020790, NIAAA R01-AA022886]; NIH, National Institute on Drug Abuse [K23 DA019809] FX This work was supported by the National Institutes of Health (NIH), National Institute on Alcohol Abuse and Alcoholism (NIAAA; grants U24-AA020794, NIAAA U01-AA020790, and NIAAA R01-AA022886) and the NIH, National Institute on Drug Abuse (grant K23 DA019809). NR 38 TC 5 Z9 5 U1 3 U2 8 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 JAN 15 PY 2016 VL 62 IS 2 BP 233 EP 239 DI 10.1093/cid/civ762 PG 7 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA DB6JW UT WOS:000368622300022 PM 26338783 ER PT J AU Hsu, DC Faldetta, KF Pei, LX Sheikh, V Utay, NS Roby, G Rupert, A Fauci, AS Sereti, I AF Hsu, Denise C. Faldetta, Kimberly F. Pei, Luxin Sheikh, Virginia Utay, Netanya S. Roby, Gregg Rupert, Adam Fauci, Anthony S. Sereti, Irini TI A Paradoxical Treatment for a Paradoxical Condition: Infliximab Use in Three Cases of Mycobacterial IRIS SO CLINICAL INFECTIOUS DISEASES LA English DT Editorial Material DE immune reconstitution inflammatory syndrome; infliximab; mycobacterial infection ID RECONSTITUTION INFLAMMATORY SYNDROME; NECROSIS-FACTOR-ALPHA; IMMUNE RECONSTITUTION; TUBERCULOSIS; PATIENT AB The management of corticosteroid refractory immune reconstitution inflammatory syndrome (IRIS) is currently unclear. Infliximab administration was associated with clinical improvement without significant adverse events in 3 patients with mycobacterial IRIS. Immunologic and virologic responses to antiretroviral therapy were unaffected. Tumor necrosis factor blockade may be beneficial for IRIS and warrants further study in clinical trials. C1 [Hsu, Denise C.; Faldetta, Kimberly F.; Pei, Luxin; Sheikh, Virginia; Roby, Gregg; Fauci, Anthony S.; Sereti, Irini] NIAID, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA. [Utay, Netanya S.] Univ Texas Med Branch, Div Infect Dis, Dept Internal Med, Galveston, TX 77555 USA. [Rupert, Adam] Leidos Biomed Res Inc, Frederick, MD USA. RP Sereti, I (reprint author), Bldg 10 Rm 11B07,10 Ctr Dr, Bethesda, MD 20814 USA. EM isereti@niaid.nih.gov OI Utay, Netanya/0000-0002-6407-8670 FU CCR NIH HHS [HHSN261200800001C]; NCI NIH HHS [HHSN261200800001E]; PHS HHS [261200800001E] NR 16 TC 2 Z9 2 U1 0 U2 1 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 JAN 15 PY 2016 VL 62 IS 2 BP 258 EP 261 DI 10.1093/cid/civ841 PG 4 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA DB6JW UT WOS:000368622300026 PM 26394669 ER PT J AU Cadet, JL Bisagno, V AF Cadet, Jean Lud Bisagno, Veronica TI Neuropsychological Consequences of Chronic Drug Use: Relevance to Treatment Approaches SO FRONTIERS IN PSYCHIATRY LA English DT Review DE marijuana; cocaine; methamphetamine; frontal cortex; cognition ID ADOLESCENT MARIJUANA USERS; ABSTINENT METHAMPHETAMINE ABUSERS; COCAINE-DEPENDENT PATIENTS; ANTERIOR CINGULATE CORTEX; SUBSTANCE USE DISORDERS; SPATIAL WORKING-MEMORY; CHRONIC CANNABIS USERS; INHIBITORY CONTROL; PREFRONTAL CORTEX; BRAIN ACTIVATION AB Heavy use of drugs impacts of the daily activities of individuals in these activities. Several groups of investigators have indeed documented changes in cognitive performance by individuals who have a long history of chronic drug use. In the case of marijuana, a wealth of information suggests that heavy long-term use of the drug may have neurobehavioral consequences in some individuals. In humans, heavy cocaine use is accompanied by neuropathological changes that might serve as substrates for cognitive dysfunctions. Similarly, methamphetamine users suffer from cognitive abnormalities that may be consequent to alterations in structures and functions. Here, we detail the evidence for these neuropsychological consequences. The review suggests that improving the care of our patients will necessarily depend on the better characterization of drug-induced cognitive phenotypes because they might inform the development of better pharmacological and behavioral interventions, with the goal of improving cognitive functions in these subsets of drug users. C1 [Cadet, Jean Lud] NIDA, Intramural Program, Mol Neuropsychiat Res Branch, Baltimore, MD USA. [Bisagno, Veronica] Univ Buenos Aires, CONICET, Inst Invest Farmacol ININFA, Buenos Aires, DF, Argentina. RP Cadet, JL (reprint author), NIDA, Intramural Program, Mol Neuropsychiat Res Branch, Baltimore, MD USA.; Bisagno, V (reprint author), Univ Buenos Aires, CONICET, Inst Invest Farmacol ININFA, Buenos Aires, DF, Argentina. EM jcadet@intra.nida.nih.gov; vbisagno@ffyb.uba.ar NR 135 TC 3 Z9 3 U1 13 U2 30 PU FRONTIERS MEDIA SA PI LAUSANNE PA PO BOX 110, EPFL INNOVATION PARK, BUILDING I, LAUSANNE, 1015, SWITZERLAND SN 1664-0640 J9 FRONT PSYCHIATRY JI Front. Psychiatry PD JAN 15 PY 2016 VL 6 AR 189 DI 10.3389/fpsyt.2015.00189 PG 10 WC Psychiatry SC Psychiatry GA DB5IR UT WOS:000368548300001 ER PT J AU Parasuram, R Mills, CL Wang, ZX Somasundaram, S Beuning, PJ Ondrechen, MJ AF Parasuram, Ramya Mills, Caitlyn L. Wang, Zhouxi Somasundaram, Saroja Beuning, Penny J. Ondrechen, Mary Jo TI Local structure based method for prediction of the biochemical function of proteins: Applications to glycoside hydrolases SO METHODS LA English DT Article DE Protein function prediction; Structurally Aligned Local Sites of Activity (SALSA); Glycoside hydrolases; Six-hairpin glycosidases; Concanavalin A-like lectin/glucanase ID XYLOGLUCAN OLIGOSACCHARIDES; FUNCTION ANNOTATION; STRUCTURE ALIGNMENT; CRYSTAL-STRUCTURE; INTERACTION SITES; 3D STRUCTURES; RESIDUES; GLUCOAMYLASE; DATABASE; SERVER AB Thousands of protein structures of unknown or uncertain function have been reported as a result of high-throughput structure determination techniques developed by Structural Genomics (SG) projects. However, many of the putative functional assignments of these SG proteins in the Protein Data Bank (PDB) are incorrect. While high-throughput biochemical screening techniques have provided valuable functional information for limited sets of SG proteins, the biochemical functions for most SG proteins are still unknown or uncertain. Therefore, computational methods for the reliable prediction of protein function from structure can add tremendous value to the existing SG data. In this article, we show how computational methods may be used to predict the function of SG proteins, using examples from the six-hairpin glycosidase (6-HG) and the concanavalin A-like lectin/glucanase (CAL/G) superfamilies. Using a set of predicted functional residues, obtained from computed electrostatic and chemical properties for each protein structure, it is shown that these superfamilies may be sorted into functional families according to biochemical function. Within these superfamilies, a total of 18 SG proteins were analyzed according to their predicted, local functional sites: 13 from the 6-HG superfamily, five from the CAL/G superfamily. Within the 6-HG superfamily, an uncharacterized protein BACOVA_03626 from Bacteroides ovatus (PDB 3ON6) and a hypothetical protein BT3781 from Bacteroides thetaiotaomicron (PDB 2P0V) are shown to have very strong active site matches with exo-alpha-1,6-mannosidases, thus likely possessing this function. Also in this superfamily, it is shown that protein BH0842, a putative glycoside hydrolase from Bacillus halodurans (PDB 2RDY), has a predicted active site that matches well with a known alpha-L-galactosidase. In the CAL/G superfamily, an uncharacterized glycosyl hydrolase family 16 protein from Mycobacterium smegmatis (PDB 3RQ0) is shown to have local structural similarity at the predicted active site with the known members of the GH16 family, with the closest match to the endoglucanase subfamily. The method discussed herein can predict whether an SG protein is correctly or incorrectly annotated and can sometimes provide a reliable functional annotation. Examples of application of the method across folds, comparing active sites between two proteins of different structural folds, are also given. (C) 2015 Elsevier Inc. All rights reserved. C1 [Parasuram, Ramya; Mills, Caitlyn L.; Wang, Zhouxi; Somasundaram, Saroja; Beuning, Penny J.; Ondrechen, Mary Jo] Northeastern Univ, Dept Chem & Chem Biol, Boston, MA 02115 USA. [Ondrechen, Mary Jo] 360 Huntington Ave, Boston, MA 02115 USA. [Parasuram, Ramya] Dana Farber Canc Inst, 450 Brookline Ave, Boston, MA 02115 USA. [Wang, Zhouxi] Natl Lib Med, Natl Ctr Biotechnol Informat, NIH, Bldg 38 A,Room 5S508,8600 Rockville Pike, Bethesda, MD 20894 USA. RP Ondrechen, MJ (reprint author), 360 Huntington Ave, Boston, MA 02115 USA. EM mjo@neu.edu FU National Science Foundation [MCB-1158176, CHE-1305655]; American Cancer Society [RSG-12-161-01-DMC]; Math Works; PhRMA Foundation FX This work is supported by the National Science Foundation under grant numbers MCB-1158176 and CHE-1305655 (PJB, MJO), the American Cancer Society under Research Scholar Grant RSG-12-161-01-DMC (PJB), Math Works, and the PhRMA Foundation (fellowship to CLM). We also thank Dr. Srinivas Somarowthu and Dr. Pengcheng Yin for their kind assistance. NR 58 TC 1 Z9 1 U1 3 U2 15 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1046-2023 EI 1095-9130 J9 METHODS JI Methods PD JAN 15 PY 2016 VL 93 BP 51 EP 63 DI 10.1016/j.ymeth.2015.11.010 PG 13 WC Biochemical Research Methods; Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA DB5LI UT WOS:000368555200007 PM 26564235 ER PT J AU Yang, PY Humphrey, SJ James, DE Yang, YH Jothi, R AF Yang, Pengyi Humphrey, Sean J. James, David E. Yang, Yee Hwa Jothi, Raja TI Positive-unlabeled ensemble learning for kinase substrate prediction from dynamic phosphoproteomics data SO BIOINFORMATICS LA English DT Article ID SPECTROMETRY-BASED PROTEOMICS; PHOSPHORYLATION SITES; MASS-SPECTROMETRY; IN-VIVO; PROTEIN-PHOSPHORYLATION; SIGNALING NETWORKS; WIDE PREDICTION; REVEALS; MOTIFS; TOOL AB Motivation: Protein phosphorylation is a post-translational modification that underlines various aspects of cellular signaling. A key step to reconstructing signaling networks involves identification of the set of all kinases and their substrates. Experimental characterization of kinase substrates is both expensive and time-consuming. To expedite the discovery of novel substrates, computational approaches based on kinase recognition sequence (motifs) from known substrates, protein structure, interaction and co-localization have been proposed. However, rarely do these methods take into account the dynamic responses of signaling cascades measured from in vivo cellular systems. Given that recent advances in mass spectrometry-based technologies make it possible to quantify phosphorylation on a proteome-wide scale, computational approaches that can integrate static features with dynamic phosphoproteome data would greatly facilitate the prediction of biologically relevant kinase-specific substrates. Results: Here, we propose a positive-unlabeled ensemble learning approach that integrates dynamic phosphoproteomics data with static kinase recognition motifs to predict novel substrates for kinases of interest. We extended a positive-unlabeled learning technique for an ensemble model, which significantly improves prediction sensitivity on novel substrates of kinases while retaining high specificity. We evaluated the performance of the proposed model using simulation studies and subsequently applied it to predict novel substrates of key kinases relevant to insulin signaling. Our analyses show that static sequence motifs and dynamic phosphoproteomics data are complementary and that the proposed integrated model performs better than methods relying only on static information for accurate prediction of kinase-specific substrates. C1 [Yang, Pengyi; Jothi, Raja] NIEHS, Syst Biol Sect, NIH, Res Triangle Pk, NC 27709 USA. [Yang, Pengyi; Jothi, Raja] NIEHS, Epigenet & Stem Cell Biol Lab, NIH, Res Triangle Pk, NC 27709 USA. [Humphrey, Sean J.] Max Planck Inst Biochem, Dept Prote & Signal Transduct, D-82152 Martinsried, Germany. [James, David E.] Univ Sydney, Sydney Med Sch, Sch Mol Biosci, Charles Perkins Ctr, Sydney, NSW 2006, Australia. [Yang, Yee Hwa] Univ Sydney, Sch Math & Stat, Sydney, NSW 2006, Australia. RP Yang, PY (reprint author), NIEHS, Syst Biol Sect, NIH, Res Triangle Pk, NC 27709 USA. EM pengyi.yang@nih.gov; jothi@mail.nih.gov RI Yang, Pengyi/B-1002-2010 OI Yang, Pengyi/0000-0003-1098-3138 FU Intramural Research Program of the NIH, National Institute of Environmental Health Sciences [1ZIAES102625] FX This work was supported by the Intramural Research Program of the NIH, National Institute of Environmental Health Sciences (1ZIAES102625 to R.J.). NR 40 TC 1 Z9 1 U1 1 U2 7 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 JAN 15 PY 2016 VL 32 IS 2 BP 252 EP 259 DI 10.1093/bioinformatics/btv550 PG 8 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 DB2SS UT WOS:000368360100013 PM 26395771 ER PT J AU Sheetlin, S Park, Y Frith, MC Spouge, JL AF Sheetlin, Sergey Park, Yonil Frith, Martin C. Spouge, John L. TI ALP & FALP: C plus plus libraries for pairwise local alignment E-values SO BIOINFORMATICS LA English DT Article ID AMINO-ACID SUBSTITUTION; SCORE DISTRIBUTIONS; SIMILARITY SEARCH; MATRICES; FASTER; DNA AB Motivation: Pairwise local alignment is an indispensable tool for molecular biologists. In real time (i.e. in about 1 s), ALP (Ascending Ladder Program) calculates the E-values for protein-protein or DNA-DNA local alignments of random sequences, for arbitrary substitution score matrix, gap costs and letter abundances; and FALP (Frameshift Ascending Ladder Program) performs a similar task, although more slowly, for frameshifting DNA-protein alignments. C1 [Sheetlin, Sergey; Park, Yonil; Spouge, John L.] Natl Lib Med, Natl Ctr Biotechnol Informat, NIH, Bethesda, MD 20894 USA. [Frith, Martin C.] Natl Inst Adv Ind Sci & Technol, Computat Biol Res Ctr, Koto Ku, Tokyo 1350064, Japan. RP Spouge, JL (reprint author), Natl Lib Med, Natl Ctr Biotechnol Informat, NIH, Bethesda, MD 20894 USA. EM spouge@nih.gov FU Intramural Research Program of the National Institutes of Health, National Library of Medicine, and National Center for Biotechnology Information; KAKENHI [26700030] FX This research was supported by the Intramural Research Program of the National Institutes of Health, National Library of Medicine, and National Center for Biotechnology Information (S.S., Y.P.,and J.L.S.) and by KAKENHI Grant Number 26700030 (M.C.F.). NR 23 TC 0 Z9 0 U1 2 U2 2 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 JAN 15 PY 2016 VL 32 IS 2 BP 304 EP 305 DI 10.1093/bioinformatics/btv575 PG 2 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 DB2SS UT WOS:000368360100024 PM 26428291 ER PT J AU de Melo, CS Feng, TS van der Westhuyzen, R Gessner, RK Street, LJ Morgans, GL Warner, DF Moosa, A Naran, K Lawrence, N Boshoff, HIM Barry, CE Harris, CJ Gordon, R Chibale, K AF de Melo, Candice Soares Feng, Tzu-Shean van der Westhuyzen, Renier Gessner, Richard K. Street, Leslie J. Morgans, Garreth L. Warner, Digby F. Moosa, Atica Naran, Krupa Lawrence, Nina Boshoff, Helena I. M. Barry, Clifton E., III Harris, C. John Gordon, Richard Chibale, Kelly TI Aminopyrazolo[1,5-a]pyrimidines as potential inhibitors of Mycobacterium tuberculosis: Structure activity relationships and ADME characterization (vol 23, pg 7240, 2015) SO BIOORGANIC & MEDICINAL CHEMISTRY LA English DT Correction C1 [de Melo, Candice Soares; Feng, Tzu-Shean; van der Westhuyzen, Renier; Gessner, Richard K.; Street, Leslie J.; Chibale, Kelly] Univ Cape Town, Dept Chem, Drug Discovery & Dev Ctr H3D, ZA-7701 Rondebosch, South Africa. [Morgans, Garreth L.] iThemba Pharmaceut, ZA-1609 Modderfontein, South Africa. [Warner, Digby F.; Moosa, Atica; Naran, Krupa] Univ Cape Town, Dept Pathol, MRC NHLS UCT Mol Mycobacteriol Res Unit, ZA-7701 Rondebosch, South Africa. [Warner, Digby F.; Chibale, Kelly] Univ Cape Town, Inst Infect Dis & Mol Med, ZA-7701 Rondebosch, South Africa. [Lawrence, Nina] Univ Cape Town, Div Clin Pharmacol, ZA-7701 Rondebosch, South Africa. [Boshoff, Helena I. M.; Barry, Clifton E., III] NIAID, TB Res Sect, Lab Clin Infect Dis, NIH, Bethesda, MD 20892 USA. [Harris, C. John] Cjh Consultants Pharmaceut R&D, Eynsford DA4 0AB, Kent, England. [Gordon, Richard] S African MRC, Strateg Hlth Innovat Partnerships, Parow Valley, South Africa. [Chibale, Kelly] Univ Cape Town, S African MRC, Drug Discovery & Dev Res Unit, ZA-7701 Rondebosch, South Africa. RP Chibale, K (reprint author), Univ Cape Town, Dept Chem, Drug Discovery & Dev Ctr H3D, ZA-7701 Rondebosch, South Africa. EM kelly.chibale@uct.ac.za RI Barry, III, Clifton/H-3839-2012 NR 1 TC 0 Z9 0 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0968-0896 EI 1464-3391 J9 BIOORGAN MED CHEM JI Bioorg. Med. Chem. PD JAN 15 PY 2016 VL 24 IS 2 BP 314 EP 314 DI 10.1016/j.bmc.2015.12.015 PG 1 WC Biochemistry & Molecular Biology; Chemistry, Medicinal; Chemistry, Organic SC Biochemistry & Molecular Biology; Pharmacology & Pharmacy; Chemistry GA CZ6TQ UT WOS:000367234300027 ER PT J AU Litzelman, K Kent, EE Rowland, JH AF Litzelman, Kristin Kent, Erin E. Rowland, Julia H. TI Social factors in informal cancer caregivers: The interrelationships among social stressors, relationship quality, and family functioning in the CanCORS data set SO CANCER LA English DT Article DE cancer; Cancer Care Outcomes Research and Surveillance (CanCORS); caregivers; family functioning; family relations; humans; interpersonal relations; negative social interaction; neoplasms; relationship quality; social stress ID CARE OUTCOMES RESEARCH; BREAST-CANCER; OF-LIFE; ASSESSMENT DEVICE; PALLIATIVE CARE; OLDER-ADULTS; SUPPORT; DEPRESSION; BURDEN; SURVIVORS AB BACKGROUNDSocial and family factors can influence the health outcomes and quality of life of informal caregivers. Little is known about the distribution and correlates of such factors for caregivers of cancer patients. This study sought to fill this gap with data from the Cancer Care Outcomes Research and Surveillance consortium. METHODSLung and colorectal cancer patients nominated an informal caregiver to participate in a caregiving survey. Caregivers reported their sociodemographic and caregiving characteristics, social stress, relationship quality with the patient, and family functioning. Descriptive statistics and Pearson correlations were used to assess the distribution of caregivers' social factors. Multivariable linear regressions assessed the independent correlates of each social factor. RESULTSMost caregivers reported low to moderate levels of social stress and good relationship quality and family functioning. In multivariable analyses, older age was associated with less social stress and better family functioning but worse relationship quality, with effect sizes (Cohen's d) up to 0.40 (P<.05). Caring for a female patient was associated with less social stress and better relationship quality but worse family functioning (effect sizes0.16, P<.05). Few caregiving characteristics were associated with social stress, whereas several were significant independent correlates of relationship quality. Finally, social factors were important independent correlates of one another. CONCLUSIONSThe results indicate the importance of personal and caregiving-related characteristics and the broader family context to social factors. Future work is needed to better understand these pathways and assess whether interventions targeting social factors can improve health or quality-of-life outcomes for informal cancer caregivers. Cancer 2016;122:278-286. (c) 2015 American Cancer Society. The distribution and correlates of social and family factors among informal caregivers are assessed in a large, multisite study of lung and colorectal cancer survivors; the importance of personal and caregiving-related characteristics and the broader family context is highlighted. The findings suggest avenues for future research that may aid in the refinement of interventions to improve cancer patient and caregiver well-being. C1 [Litzelman, Kristin; Kent, Erin E.; Rowland, Julia H.] NCI, Rockville, MD USA. RP Litzelman, K (reprint author), NCI, Div Canc Control & Populat Sci, 9609 Med Ctr Dr,MSC 9761,3E-620, Bethesda, MD 20892 USA. EM kristin.litzelman@nih.gov FU National Cancer Institute [U01 CA93324, U01 CA93326, U01 CA93329, U01 CA93332, U01 CA93339, U01 CA93344, U01 CA93348]; Department of Veterans Affairs [CRS 02-164] FX The Cancer Care Outcomes Research and Surveillance consortium data were collected with funding from the National Cancer Institute (U01 CA93324, U01 CA93326, U01 CA93329, U01 CA93332, U01 CA93339, U01 CA93344, and U01 CA93348) and the Department of Veterans Affairs (CRS 02-164). The article was prepared as part of the authors' official duties as employees of the US Federal Government. NR 45 TC 0 Z9 0 U1 7 U2 12 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0008-543X EI 1097-0142 J9 CANCER-AM CANCER SOC JI Cancer PD JAN 15 PY 2016 VL 122 IS 2 BP 278 EP 286 DI 10.1002/cncr.29741 PG 9 WC Oncology SC Oncology GA DA7UK UT WOS:000368009600017 PM 26479767 ER PT J AU Tavoulari, S Margheritis, E Nagarajan, A DeWitt, DC Zhang, YW Rosado, E Ravera, S Rhoades, E Forrest, LR Rudnick, G AF Tavoulari, Sotiria Margheritis, Eleonora Nagarajan, Anu DeWitt, David C. Zhang, Yuan-Wei Rosado, Edwin Ravera, Silvia Rhoades, Elizabeth Forrest, Lucy R. Rudnick, Gary TI Two Na+ Sites Control Conformational Change in a Neurotransmitter Transporter Homolog SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID PARTICLE MESH EWALD; BINDING-SITE; SEROTONIN TRANSPORTER; ALTERNATING-ACCESS; SODIUM SYMPORTERS; MOLECULAR-DYNAMICS; BACTERIAL HOMOLOG; CRYSTAL-STRUCTURE; DOPAMINE TRANSPORTER; POTENTIAL FUNCTIONS AB In LeuT, a prokaryotic homolog of neurotransmitter transporters, Na+ stabilizes outward-open conformational states. We examined how each of the two LeuT Na+ binding sites contributes to Na+ -dependent closure of the cytoplasmic pathway using biochemical and biophysical assays of conformation. Mutating either of two residues that contribute to the Na2 site completely prevented cytoplasmic closure in response to Na+, suggesting that Na2 is essential for this conformational change, whereas Na1 mutants retained Na+ responsiveness. However, mutation of Na1 residues also influenced the Na+ -dependent conformational change in ways that varied depending on the position mutated. Computational analyses suggest those mutants influence the ability of Na1 binding to hydrate the substrate pathway and perturb an interaction network leading to the extracellular gate. Overall, the results demonstrate that occupation of Na2 stabilizes outward-facing conformations presumably through a direct interaction between Na+ and transmembrane helices 1 and 8, whereas Na+ binding at Na1 influences conformational change through a network of intermediary interactions. The results also provide evidence that N-terminal release and helix motions represent distinct steps in cytoplasmic pathway opening. C1 [Tavoulari, Sotiria; Margheritis, Eleonora; Zhang, Yuan-Wei; Rosado, Edwin; Ravera, Silvia; Rudnick, Gary] Yale Univ, Dept Pharmacol, New Haven, CT 06520 USA. [DeWitt, David C.; Rhoades, Elizabeth] Yale Univ, Dept Mol Biophys & Biochem, New Haven, CT 06520 USA. [Nagarajan, Anu; Forrest, Lucy R.] NINDS, Computat Struct Biol Sect, NIH, Rockville, MD 20852 USA. RP Rudnick, G (reprint author), Yale Univ, Dept Pharmacol, 333 Cedar St, New Haven, CT 06520 USA. EM gary.rudnick@yale.edu FU Division of Intramural Research of the National Institutes of Health, NINDS; National Institute on Drug Abuse [DA007259, DA008213]; NINDS [NS079955] FX This work was supported in part by the Division of Intramural Research of the National Institutes of Health, NINDS (to L.R.F.), National Institute on Drug Abuse Grants DA007259 and DA008213 (to G.R.), and NINDS Grant NS079955 (to E. Rhoads). The authors declare that they have no conflicts of interest with the contents of this article. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. Downloaded from http://www.jbc.org/at ISI, Thomson Scientific on January 17, 2016 NR 79 TC 8 Z9 8 U1 2 U2 14 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 EI 1083-351X J9 J BIOL CHEM JI J. Biol. Chem. PD JAN 15 PY 2016 VL 291 IS 3 BP 1456 EP 1471 PG 16 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA DA8PR UT WOS:000368068300036 PM 26582198 ER PT J AU Wan, CK He, C Sun, L Egwuagu, CE Leonard, WJ AF Wan, Chi-Keung He, Chang Sun, Lin Egwuagu, Charles E. Leonard, Warren J. TI Cutting Edge: IL-1 Receptor Signaling is Critical for the Development of Autoimmune Uveitis SO JOURNAL OF IMMUNOLOGY LA English DT Article ID T(H)17 CELLS; DISEASES; INFLAMMATION; COMPONENTS; INDUCTION; NLRP3 AB IL-1 beta is a proinflammatory cytokine important for local and systemic immunity. However, aberrant production of this cytokine is implicated in pathogenic mechanisms of a number of inflammatory diseases, including Behcet's disease and age-related macular degeneration. In this study, we report the increased secretion of IL-1 beta in the retina by neutrophils, macrophages, and dendritic cells during ocular inflammation and show that loss of IL-1R signaling confers protection from experimental autoimmune uveitis. Moreover, the amelioration of experimental autoimmune uveitis in Il1r-deficient mice was associated with reduced infiltration of inflammatory cells into the retina and decreased numbers of uveitogenic Th17 cells that mediate uveitis. These findings indicate the possible utility of IL-1R-blocking agents for the treatment of ocular inflammatory diseases. C1 [Wan, Chi-Keung; Leonard, Warren J.] NHLBI, Lab Mol Immunol, NIH, Bethesda, MD 20892 USA. [Wan, Chi-Keung; Leonard, Warren J.] NHLBI, Ctr Immunol, NIH, Bethesda, MD 20892 USA. [He, Chang; Sun, Lin; Egwuagu, Charles E.] NEI, Mol Immunol Sect, NIH, Bethesda, MD 20892 USA. RP Leonard, WJ (reprint author), NHLBI, Lab Mol Immunol, NIH, Bldg 10,Room 7B05,10 Ctr Dr, Bethesda, MD 20892 USA. EM egwuaguc@nei.nih.gov; wjl@helix.nih.gov RI Sun, Lin/I-3146-2016 FU Division of Intramural Research, National Heart, Lung, and Blood Institute; National Eye Institute FX This work was supported by the Division of Intramural Research, National Heart, Lung, and Blood Institute and by the National Eye Institute. NR 18 TC 3 Z9 3 U1 0 U2 4 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 JAN 15 PY 2016 VL 196 IS 2 BP 543 EP 546 DI 10.4049/jimmunol.1502080 PG 4 WC Immunology SC Immunology GA DA8QX UT WOS:000368072100009 PM 26643477 ER PT J AU Vural, A Al-Khodor, S Cheung, GYC Shi, CS Srinivasan, L McQuiston, TJ Hwang, IY Yeh, AJ Blumer, JB Briken, V Williamson, PR Otto, M Fraser, IDC Kehrl, JH AF Vural, Ali Al-Khodor, Souhaila Cheung, Gordon Y. C. Shi, Chong-Shan Srinivasan, Lalitha McQuiston, Travis J. Hwang, Il-Young Yeh, Anthony J. Blumer, Joe B. Briken, Volker Williamson, Peter R. Otto, Michael Fraser, Iain D. C. Kehrl, John H. TI Activator of G-Protein Signaling 3-Induced Lysosomal Biogenesis Limits Macrophage Intracellular Bacterial Infection SO JOURNAL OF IMMUNOLOGY LA English DT Article ID BURKHOLDERIA-CENOCEPACIA; MEMBRANE-PROTEINS; REGULATOR AGS3; HT-29 CELLS; BETA-GAMMA; AUTOPHAGY; DISEASE; SEEKING; MACROAUTOPHAGY; EXPRESSION AB Many intracellular pathogens cause disease by subverting macrophage innate immune defense mechanisms. Intracellular pathogens actively avoid delivery to or directly target lysosomes, the major intracellular degradative organelle. In this article, we demonstrate that activator of G-protein signaling 3 (AGS3), an LPS-inducible protein in macrophages, affects both lysosomal biogenesis and activity. AGS3 binds the Gi family of G proteins via its G-protein regulatory (GoLoco) motif, stabilizing the G alpha subunit in its GDP-bound conformation. Elevated AGS3 levels in macrophages limited the activity of the mammalian target of rapamycin pathway, a sensor of cellular nutritional status. This triggered the nuclear translocation of transcription factor EB, a known activator of lysosomal gene transcription. In contrast, AGS3-deficient macrophages had increased mammalian target of rapamycin activity, reduced transcription factor EB activity, and a lower lysosomal mass. High levels of AGS3 in macrophages enhanced their resistance to infection by Burkholderia cenocepacia J2315, Mycobacterium tuberculosis, and methicillin-resistant Staphylococcus aureus, whereas AGS3-deficient macrophages were more susceptible. We conclude that LPS priming increases AGS3 levels, which enhances lysosomal function and increases the capacity of macrophages to eliminate intracellular pathogens. C1 [Vural, Ali; Shi, Chong-Shan; Hwang, Il-Young; Kehrl, John H.] NIAID, B Cell Mol Immunol Sect, Immunoregulat Lab, NIH, Bethesda, MD 20892 USA. [Al-Khodor, Souhaila; Fraser, Iain D. C.] NIAID, Signaling Syst Unit, Lab Syst Biol, NIH, Bethesda, MD 20892 USA. [Cheung, Gordon Y. C.; Yeh, Anthony J.; Otto, Michael] NIAID, Pathogen Mol Genet Sect, Lab Human Bacterial Pathogenesis, NIH, Bethesda, MD 20892 USA. [Srinivasan, Lalitha; Briken, Volker] Univ Maryland, Dept Cell Biol & Mol Genet, College Pk, MD 20742 USA. [McQuiston, Travis J.; Williamson, Peter R.] NIAID, Translat Mycol Unit, Lab Clin Infect Dis, NIH, Bethesda, MD 20892 USA. [Blumer, Joe B.] Med Univ S Carolina, Dept Cell & Mol Pharmacol & Expt Therapeut, Charleston, SC 29425 USA. RP Kehrl, JH (reprint author), NIAID, B Cell Mol Immunol Sect, Immunoregulat Lab, NIH, 10 Ctr Dr,MSC 1876,Bldg 10,Room 11N212, Bethesda, MD 20892 USA. EM jkehrl@niaid.nih.gov RI di Ronza, Alberto/H-7674-2016; OI di Ronza, Alberto/0000-0002-9813-5143; Blumer, Joe/0000-0002-0020-3815; Otto, Michael/0000-0002-2222-4115; Al Khodor, Souhaila/0000-0003-4858-7130; Briken, Volker/0000-0001-5830-6107 FU National Institute of Allergy and Infectious Diseases FX This work was supported by the intramural program of the National Institute of Allergy and Infectious Diseases. NR 50 TC 2 Z9 2 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 EI 1550-6606 J9 J IMMUNOL JI J. Immunol. PD JAN 15 PY 2016 VL 196 IS 2 BP 846 EP 856 DI 10.4049/jimmunol.1501595 PG 11 WC Immunology SC Immunology GA DA8QX UT WOS:000368072100039 PM 26667172 ER PT J AU Popescu, I Pipeling, MR Mannem, H Shah, PD Orens, JB Connors, M Migueles, SA McDyer, JF AF Popescu, Iulia Pipeling, Matthew R. Mannem, Hannah Shah, Pali D. Orens, Jonathan B. Connors, Mark Migueles, Stephen A. McDyer, John F. TI IL-12-Dependent Cytomegalovirus-Specific CD4(+) T Cell Proliferation, T-bet Induction, and Effector Multifunction during Primary Infection Are Key Determinants for Early Immune Control SO JOURNAL OF IMMUNOLOGY LA English DT Article ID BRONCHIOLITIS-OBLITERANS-SYNDROME; I HEAVY-CHAINS; HUMAN-IMMUNODEFICIENCY-VIRUS; LUNG-TRANSPLANT RECIPIENTS; RESISTANT CYTOMEGALOVIRUS; ANTIGEN PRESENTATION; TRANSCRIPTION FACTOR; T(H)1 CELLS; LYMPHOCYTES; CMV AB CMV remains an important opportunistic pathogen in solid organ and hematopoietic cell transplantation, particularly in lung transplant recipients (LTRs). LTRs mismatched for CMV (donor(+)/recipient(-); D+R-) are at high risk for active CMVinfection and increased mortality; however, the immune correlates of viral control remain incompletely understood. We prospectively studied 27 D+R- LTRs during primary CMV infection to determine whether acute CD4(+) T cell parameters differentiated the capacity for viral control during early chronic infection. Unexpectedly, the T-box transcription factor, T-bet, was expressed at low levels in CD4(+) compared with CD8(+) T cells during acute primary infection. However, the capacity for in vitro CMV phosphoprotein 65-specific proliferation and CD4(+) T-bet(+) induction differentiated LTR controllers from early viremic relapsers, correlating with granzyme B loading and effector multifunction. Furthermore, impaired CMV-specific proliferative responses from relapsers, along with T-bet, and effector function could be significantly rescued, most effectively with phosphoprotein 65 Ag and combined exogenous IL-2 and IL-12. Acute CD4(+) T cell CMV-specific proliferative and effector responses were highly IL-12-dependent in blocking studies. In addition, we generated monocyte-derived dendritic cells using PBMC obtained during primary infection from relapsers and observed impaired monocyte-derived dendritic cell differentiation, a reduced capacity for IL-12 production, but increased IL-10 production compared with controls, suggesting an APC defect during acute CMV viremia. Taken together, these data show an important role for CMV-specific CD4(+) effector responses in differentiating the capacity of high- risk LTRs to establish durable immune control during early chronic infection and provide evidence for IL-12 as a key factor driving these responses. C1 [Popescu, Iulia; Pipeling, Matthew R.; Mannem, Hannah; McDyer, John F.] Univ Pittsburgh, Sch Med, Div Pulm Allergy & Crit Care Med, Dept Med, Pittsburgh, PA 15213 USA. [Shah, Pali D.; Orens, Jonathan B.] Johns Hopkins Univ, Sch Med, Dept Med, Div Pulm & Crit Care Med, Baltimore, MD 21205 USA. [Connors, Mark; Migueles, Stephen A.] NIAID, Immunoregulat Lab, NIH, Bethesda, MD 20892 USA. RP McDyer, JF (reprint author), Univ Pittsburgh, Sch Med, Div Pulm Allergy & Crit Care Med, 3459 Fifth Ave,NW 628, Pittsburgh, PA 15213 USA. EM mcdyerjf@upmc.edu FU National Institutes of Health [R01-AI079175] FX This work was supported by National Institutes of Health Grant R01-AI079175 ( to J.F.M.). NR 55 TC 3 Z9 3 U1 2 U2 8 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 EI 1550-6606 J9 J IMMUNOL JI J. Immunol. PD JAN 15 PY 2016 VL 196 IS 2 BP 877 EP 890 DI 10.4049/jimmunol.1501589 PG 14 WC Immunology SC Immunology GA DA8QX UT WOS:000368072100042 PM 26663780 ER PT J AU Leshner, M Devine, M Roloff, GW True, LD Misteli, T Meaburn, KJ AF Leshner, Marc Devine, Michelle Roloff, Gregory W. True, Lawrence D. Misteli, Tom Meaburn, Karen J. TI Locus-specific gene repositioning in prostate cancer SO MOLECULAR BIOLOGY OF THE CELL LA English DT Article ID NUCLEAR LAMINA INTERACTIONS; CHROMATIN DECONDENSATION; GENOME ORGANIZATION; SCHISTOSOMA-MANSONI; INTERPHASE NUCLEUS; ACTIVATED GENES; SYNDROME CELLS; CHROMOSOME; REORGANIZATION; HETEROCHROMATIN AB Genes occupy preferred spatial positions within interphase cell nuclei. However, positioning patterns are not an innate feature of a locus, and genes can alter their localization in response to physiological and pathological changes. Here we screen the radial positioning patterns of 40 genes in normal, hyperplasic, and malignant human prostate tissues. We find that the overall spatial organization of the genome in prostate tissue is largely conserved among individuals. We identify three genes whose nuclear positions are robustly altered in neoplastic prostate tissues. FLI1 and MMP9 position differently in prostate cancer than in normal tissue and prostate hyperplasia, whereas MMP2 is repositioned in both prostate cancer and hyperplasia. Our data point to locus-specific reorganization of the genome during prostate disease. C1 [Leshner, Marc; Devine, Michelle; Roloff, Gregory W.; Misteli, Tom; Meaburn, Karen J.] NCI, NIH, Bethesda, MD 20892 USA. [True, Lawrence D.] Univ Washington, Dept Pathol, Seattle, WA 98195 USA. RP Misteli, T (reprint author), NCI, NIH, Bethesda, MD 20892 USA. EM mistelit@mail.nih.gov; meaburnk@mail.nih.gov OI Meaburn, Karen/0000-0002-1327-5957 FU Department of Defense Idea Award [W81XWH-12-1-0224]; National Cancer Institute, National Institutes of Health, under Pacific Northwest Prostate Cancer SPORE Grant [P50CA097186]; Intramural Research Program of the National Institutes of Health, National Cancer Institute, Center for Cancer Research FX We thank Prabhakar Gudla and Stephen Lockett for help with image analysis; Olufunmilayo Agunloye for technical assistance; Delft University of Technology for providing the DIPImage and PRTools toolboxes; and Tatiana Karpova for microscopy support. We also thank Kathy Doan for help in identifying and obtaining tissue used for this study. Fluorescence imaging was performed at the National Cancer Institute Fluorescence Imaging Facility (Bethesda, MD). This work was supported by Department of Defense Idea Award W81XWH-12-1-0224, the National Cancer Institute, National Institutes of Health, under Pacific Northwest Prostate Cancer SPORE Grant P50CA097186, and, in part, by the Intramural Research Program of the National Institutes of Health, National Cancer Institute, Center for Cancer Research. NR 55 TC 5 Z9 5 U1 0 U2 0 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 EI 1939-4586 J9 MOL BIOL CELL JI Mol. Biol. Cell PD JAN 15 PY 2016 VL 27 IS 2 BP 236 EP 246 DI 10.1091/mbc.E15-05-0280 PG 11 WC Cell Biology SC Cell Biology GA DB0YB UT WOS:000368233300003 PM 26564800 ER PT J AU Xu, S Cherok, E Das, S Li, SA Roelofs, BA Ge, SX Polster, BM Boyman, L Lederer, WJ Wang, CX Karbowski, M AF Xu, Shan Cherok, Edward Das, Shweta Li, Sunan Roelofs, Brian A. Ge, Shealinna X. Polster, Brian M. Boyman, Liron Lederer, W. Jonathan Wang, Chunxin Karbowski, Mariusz TI Mitochondrial E3 ubiquitin ligase MARCH5 controls mitochondrial fission and cell sensitivity to stress-induced apoptosis through regulation of MiD49 protein SO MOLECULAR BIOLOGY OF THE CELL LA English DT Article ID DRP1 RECRUITMENT; DYNAMICS; FUSION; MEMBRANE; MID51; MFF; ACTIVATION; MORPHOLOGY; PROMOTES; SURVIVAL AB Ubiquitin-and proteasome-dependent outer mitochondrial membrane (OMM)associated degradation (OMMAD) is critical for mitochondrial and cellular homeostasis. However, the scope and molecular mechanisms of the OMMAD pathways are still not well understood. We report that the OMM-associated E3 ubiquitin ligase MARCH5 controls dynamin-related protein 1 (Drp1)-dependent mitochondrial fission and cell sensitivity to stress-induced apoptosis. MARCH5 knockout selectively inhibited ubiquitination and proteasomal degradation of MiD49, a mitochondrial receptor of Drp1, and consequently led to mitochondrial fragmentation. Mitochondrial fragmentation in MARCH5-/-cells was not associated with inhibition of mitochondrial fusion or bioenergetic defects, supporting the possibility that MARCH5 is a negative regulator of mitochondrial fission. Both MARCH5 re-expression and MiD49 knockout in MARCH5-/-cells reversed mitochondrial fragmentation and reduced sensitivity to stress-induced apoptosis. These findings and data showing MARCH5-dependent degradation of MiD49 upon stress support the possibility that MARCH5 regulation of MiD49 is a novel mechanism controlling mitochondrial fission and, consequently, the cellular response to stress. C1 [Xu, Shan; Cherok, Edward; Das, Shweta; Li, Sunan; Roelofs, Brian A.; Boyman, Liron; Lederer, W. Jonathan; Karbowski, Mariusz] Univ Maryland, Sch Med, Ctr Biomed Engn & Technol, Baltimore, MD 21201 USA. [Xu, Shan; Cherok, Edward; Das, Shweta; Li, Sunan; Roelofs, Brian A.; Karbowski, Mariusz] Univ Maryland, Sch Med, Dept Biochem & Mol Biol, Baltimore, MD 21201 USA. [Roelofs, Brian A.; Ge, Shealinna X.; Polster, Brian M.] Univ Maryland, Sch Med, Dept Anesthesiol, Baltimore, MD 21201 USA. [Roelofs, Brian A.; Ge, Shealinna X.; Polster, Brian M.] Univ Maryland, Sch Med, Shock Trauma & Anesthesiol Res STAR Ctr, Baltimore, MD 21201 USA. [Boyman, Liron; Lederer, W. Jonathan] Univ Maryland, Sch Med, Dept Physiol, Baltimore, MD 21201 USA. [Wang, Chunxin] NINDS, Biochem Sect, Surg Neurol Branch, NIH, Bethesda, MD 20892 USA. RP Karbowski, M (reprint author), Univ Maryland, Sch Med, Ctr Biomed Engn & Technol, Baltimore, MD 21201 USA. EM mkarbowski@umaryland.edu RI Wang, Chunxin/B-9312-2016 OI Wang, Chunxin/0000-0001-6015-6806 FU National Institutes of Health (NIH) [R01 NS085165, R01 HL105239, U01 HL116321, R01 GM083131, R01 GM102177]; American Heart Association [15SDG22100002]; Intramural Research Program of the National Institute of Neurological Disorders and Stroke, NIH FX The authors thank Alma Arnold for help with Airyscan imaging, Carl Zeiss Microscopy for access to an LSM 880/Airyscan imaging system, Ferenc Livak and other members of the Shared Flow Services Facility for help with cell sorting, Pamela Wright for insightful comments on the manuscript, and Mervyn Monteiro for anti-MYC antibody. The authors also acknowledge financial support from the National Institutes of Health (NIH): R01 NS085165 (B.M.P.), R01 HL105239 and U01 HL116321 (W.J.L.), and R01 GM083131 and R01 GM102177 (M.K.), and American Heart Association 15SDG22100002 (L.B.). C.W. is supported in part by the Intramural Research Program of the National Institute of Neurological Disorders and Stroke, NIH. NR 38 TC 5 Z9 5 U1 0 U2 1 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 EI 1939-4586 J9 MOL BIOL CELL JI Mol. Biol. Cell PD JAN 15 PY 2016 VL 27 IS 2 BP 349 EP 359 DI 10.1091/mbc.E15-09-0678 PG 11 WC Cell Biology SC Cell Biology GA DB0YB UT WOS:000368233300011 PM 26564796 ER PT J AU Byrd, AL Segre, JA AF Byrd, Allyson L. Segre, Julia A. TI Adapting Koch's postulates SO SCIENCE LA English DT Editorial Material ID COLONIZATION RESISTANCE; CLOSTRIDIUM-DIFFICILE; PATHOGENS; DISEASE C1 [Byrd, Allyson L.; Segre, Julia A.] NHGRI, Microbial Genom Sect, Translat & Funct Genom Branch, Bethesda, MD 20892 USA. [Byrd, Allyson L.] Boston Univ, Dept Bioinformat, Boston, MA 02215 USA. RP Byrd, AL (reprint author), NHGRI, Microbial Genom Sect, Translat & Funct Genom Branch, Bethesda, MD 20892 USA. EM jsegre@nhgri.nih.gov NR 14 TC 18 Z9 18 U1 9 U2 21 PU AMER ASSOC ADVANCEMENT SCIENCE PI WASHINGTON PA 1200 NEW YORK AVE, NW, WASHINGTON, DC 20005 USA SN 0036-8075 EI 1095-9203 J9 SCIENCE JI Science PD JAN 15 PY 2016 VL 351 IS 6270 BP 224 EP 226 DI 10.1126/science.aad6753 PG 3 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA DA9AM UT WOS:000368098600018 PM 26816362 ER PT J AU Yang, N AF Yang, Nora TI Orphan The Quest to Save Children with Rare Genetic Disorders SO SCIENCE LA English DT Book Review C1 [Yang, Nora] NIH, Natl Ctr Adv Translat Sci, Bethesda, MD 20892 USA. RP Yang, N (reprint author), NIH, Natl Ctr Adv Translat Sci, Bethesda, MD 20892 USA. EM nora.yang@nih.gov NR 1 TC 0 Z9 0 U1 4 U2 4 PU AMER ASSOC ADVANCEMENT SCIENCE PI WASHINGTON PA 1200 NEW YORK AVE, NW, WASHINGTON, DC 20005 USA SN 0036-8075 EI 1095-9203 J9 SCIENCE JI Science PD JAN 15 PY 2016 VL 351 IS 6270 BP 233 EP 233 DI 10.1126/science.aad7104 PG 1 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA DA9AM UT WOS:000368098600024 ER PT J AU Baker, SG Kramer, BS Lindeman, KS AF Baker, Stuart G. Kramer, Barnett S. Lindeman, Karen S. TI Latent class instrumental variables: a clinical and biostatistical perspective SO STATISTICS IN MEDICINE LA English DT Article DE all-or-none compliance; causal inference; encouragement design; observational; paired availability design; principal stratification; randomized trial ID PAIRED AVAILABILITY DESIGN; SURROGATE END-POINTS; OR-NONE COMPLIANCE; TO-TREAT ANALYSIS; RANDOMIZED-TRIAL; PRINCIPAL STRATIFICATION; CAUSAL INFERENCE; ESTIMATING EFFICACY; RECEIVING TREATMENT; BAYESIAN-APPROACH AB In some two-arm randomized trials, some participants receive the treatment assigned to the other arm as a result of technical problems, refusal of a treatment invitation, or a choice of treatment in an encouragement design. In some before-and-after studies, the availability of a new treatment changes from one time period to this next. Under assumptions that are often reasonable, the latent class instrumental variable (IV) method estimates the effect of treatment received in the aforementioned scenarios involving all-or-none compliance and all-or-none availability. Key aspects are four initial latent classes (sometimes called principal strata) based on treatment received if in each randomization group or time period, the exclusion restriction assumption (in which randomization group or time period is an instrumental variable), the monotonicity assumption (which drops an implausible latent class from the analysis), and the estimated effect of receiving treatment in one latent class (sometimes called efficacy, the local average treatment effect, or the complier average causal effect). Since its independent formulations in the biostatistics and econometrics literatures, the latent class IV method (which has no well-established name) has gained increasing popularity. We review the latent class IV method from a clinical and biostatistical perspective, focusing on underlying assumptions, methodological extensions, and applications in our fields of obstetrics and cancer research. Copyright (C) 2015 John Wiley & Sons, Ltd. C1 [Baker, Stuart G.; Kramer, Barnett S.] Natl Canc Inst, Canc Prevent Div, Bethesda, MD 20892 USA. [Lindeman, Karen S.] Johns Hopkins Med Inst, Dept Anesthesiol, Baltimore, MD 21205 USA. RP Baker, SG (reprint author), Natl Canc Inst, Canc Prevent Div, 9609 Med Ctr Dr,5E638, Bethesda, MD 20892 USA. EM sb16i@nih.gov FU National Institutes of Health FX This work was supported by the National Institutes of Health. NR 69 TC 1 Z9 1 U1 0 U2 3 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0277-6715 EI 1097-0258 J9 STAT MED JI Stat. Med. PD JAN 15 PY 2016 VL 35 IS 1 BP 147 EP 160 DI 10.1002/sim.6612 PG 14 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 DA7GF UT WOS:000367971900010 PM 26239275 ER PT J AU Preisig, M Strippoli, MPF Castelao, E Merikangas, KR Gholam-Rezaee, M Marquet, P Aubry, JM Vandeleur, CL AF Preisig, Martin Strippoli, Marie-Pierre F. Castelao, Enrique Merikangas, Kathleen Ries Gholam-Rezaee, Mehdi Marquet, Pierre Aubry, Jean-Michel Vandeleur, Caroline L. TI The specificity of the familial aggregation of early-onset bipolar disorder: A controlled 10-year follow-up study of offspring of parents with mood disorders SO JOURNAL OF AFFECTIVE DISORDERS LA English DT Article DE Mania; Age of onset; Family aggregation; High-risk study; Major depression; Substance use disorders ID INTER-INFORMANT AGREEMENT; MAJOR DEPRESSIVE DISORDER; TEST-RETEST RELIABILITY; SUBSTANCE USE DISORDERS; GENETIC-STUDIES DIGS; HISTORY METHOD; DIAGNOSTIC INTERVIEW; I DISORDER; PSYCHIATRIC-DISORDERS; UNIPOLAR DEPRESSION AB Background: Two major sources of heterogeneity of mood disorders that have been demonstrated in clinical, family and genetic studies are the mood disorder subtype (i.e. bipolar (BPD) and major depressive disorder (MDD)) and age of onset of mood episodes. Using a prospective high-risk study design, our aims were to test the specificity of the parent-child transmission of BPD and MDD and to establish the risk of psychopathology in offspring in function of the age of onset of the parental disorder. Methods: Clinical information was collected on 208 probands (n=81 with BPD, n=64 with MDD, n=63 medical controls) as well as their 202 spouses and 372 children aged 6-17 years at study entry. Parents and children were directly interviewed every 3 years (mean duration of follow-up=10.6 years). Parental age of onset was dichotomized at age 21. Results: Offspring of parents with early onset BPD entailed a higher risk of BPD HR=7.9(1.8-34.6) and substance use disorders HR=5.0(1.1-21.9) than those with later onset and controls. Depressive disorders were not significantly increased in offspring regardless of parental mood disorder subtype or age of onset. Limitations: Limited sample size, age of onset in probands was obtained retrospectively, age of onset in co-parents was not adequately documented, and a quarter of the children had no direct interview. Conclusions: Our results provide support for the independence of familial aggregation of BPD from MDD and the heterogeneity of BPD based on patterns of onset. Future studies should further investigate correlates of early versus later onset BPD. (C) 2015 Elsevier B.V. All rights reserved. C1 [Preisig, Martin; Strippoli, Marie-Pierre F.; Castelao, Enrique; Gholam-Rezaee, Mehdi; Marquet, Pierre; Vandeleur, Caroline L.] Univ Lausanne Hosp, Dept Psychiat, CH-1008 Prilly, Switzerland. [Merikangas, Kathleen Ries] NIMH, Genet Epidemiol Res Branch, Intramural Res Program, Bethesda, MD 20892 USA. [Aubry, Jean-Michel] Univ Hosp Geneva, Dept Mental Hlth & Psychiat, Geneva, Switzerland. RP Vandeleur, CL (reprint author), Univ Lausanne Hosp, Dept Psychiat, Site Cery, CH-1008 Prilly, Switzerland. EM Caroline.Vandeleur@chuv.ch RI Strippoli, Marie-Pierre/K-8164-2013; Preisig, Martin/H-3441-2016; OI Strippoli, Marie-Pierre/0000-0003-3053-484X; Castelao, Enrique/0000-0003-1966-3683 FU Swiss National Foundation (SNF) [3200-040677, 32003B-105969, 32003B-118326, 3200-049746, 3200-061974]; Swiss National Foundation [125759]; GlaxoSmithKline Clinical Genetics FX This research was supported by five grants from the Swiss National Foundation (SNF: #3200-040677, #32003B-105969, and #32003B-118326 to F. Ferrero; #3200-049746 and #3200-061974 to M. Preisig), a grant for a national research project (#125759 to P. Magistretti) financed by the Swiss National Foundation, and a grant from GlaxoSmithKline Clinical Genetics. The funders had no involvement in any aspect of this study. NR 58 TC 6 Z9 6 U1 1 U2 10 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0165-0327 EI 1573-2517 J9 J AFFECT DISORDERS JI J. Affect. Disord. PD JAN 15 PY 2016 VL 190 BP 26 EP 33 DI 10.1016/j.jad.2015.10.005 PG 8 WC Clinical Neurology; Psychiatry SC Neurosciences & Neurology; Psychiatry GA CY5QT UT WOS:000366463000006 PM 26480208 ER PT J AU Lener, MS Kundu, P Wong, E Dewilde, KE Tang, CY Balchandani, P Murrough, JW AF Lener, Marc S. Kundu, Prantik Wong, Edmund Dewilde, Kaitlin E. Tang, Cheuk Y. Balchandani, Priti Murrough, James W. TI Cortical abnormalities and association with symptom dimensions across the depressive spectrum SO JOURNAL OF AFFECTIVE DISORDERS LA English DT Article ID GRAY-MATTER VOLUME; RAPID ANTIDEPRESSANT RESPONSE; PREFRONTAL CORTEX ACTIVITY; VOXEL-BASED MORPHOMETRY; DOMAIN CRITERIA RDOC; ANALOG MOOD SCALE; MAJOR DEPRESSION; ANTERIOR CINGULATE; FUNCTIONAL CONNECTIVITY; EXCITATORY SYNAPSES AB Background: Few studies have investigated the relationship between structural brain abnormalities and dimensions of depressive symptomatology. Methods: In the current study, we examined the relationship between cortical structural abnormalities and specific behavioral dimensions relevant to depression in a sample of unmedicated patients with major depressive disorder (MDD, n=57) and demographically similar healthy control volunteers (HC, n=29). All subjects underwent diagnostic assessment with the SCID, MRI at 3T, and dimensional assessments using the visual analog scales (VAS). Cortical regions were extracted for each subject, and group comparisons of cortical volume (CV), surface area (SA), and cortical thickness (CT) were performed controlling for multiple comparisons using a bootstrapping technique. Regions demonstrating group differences were analyzed for correlation with specific dimensions assessments. Results: As compared with HC, MDD subjects exhibited reduced CV within the left supramarginal gyms, right ventrolateral prefrontal cortex (VLPFC), entorhinal cortex, parahippocampal gyms, fusiform gyrus and pericalcarine; reduced SA in the right VLPFC, cuneus, and left temporal pole; and reduced CT in the right rostral anterior cingulate cortex (rACC) (all p's < 0.05, corrected). The largest effect occurred within the right VLPFC for CV and SA (MDD < HC; effect sizes: 0.60). CV in the right VLPFC inversely correlated with sadness, fatigue and worry; CT in the right rACC inversely correlated with irritability and fatigue. Limitations: Future studies will be required to further map the anatomical changes in depression to behavioral dimensions. Conclusions: Our results indicate that specific cortical abnormalities are associated with specific behavioral components linked to depression. (C) 2015 Elsevier B.V. All rights reserved. C1 [Lener, Marc S.] NIH, Expt Therapeut & Pathophysiol Branch, Bethesda, MD 20892 USA. [Kundu, Prantik; Wong, Edmund; Tang, Cheuk Y.; Balchandani, Priti] Icahn Sch Med Mt Sinai, Dept Radiol, Translat & Mol Imaging Inst, New York, NY 10029 USA. [Dewilde, Kaitlin E.; Murrough, James W.] Icahn Sch Med Mt Sinai, Dept Psychiat, Mood & Anxiety Disorders Program, New York, NY 10029 USA. [Murrough, James W.] Icahn Sch Med Mt Sinai, Fishberg Dept Neurosci, New York, NY 10029 USA. [Murrough, James W.] Icahn Sch Med Mt Sinai, Friedman Brain Inst, New York, NY 10029 USA. RP Murrough, JW (reprint author), Icahn Sch Med Mt Sinai, Dept Psychiat, Mood & Anxiety Disorders Program, One Gustave L Levy Pl,Box 1230, New York, NY 10029 USA. EM james.murrough@mssm.edu RI Murrough, James/J-7129-2013; OI Murrough, James/0000-0001-6286-1242; Kundu, Prantik/0000-0001-9367-3068 FU National Institute of Mental Health of the National Institutes of Health [K23MH094707]; Iris & Junming Le Foundation; Brain and Behavior Research Foundation (NARSAD); NIH National Center for Advancing Translational Sciences [UL1TR000067] FX This work was supported by the National Institute of Mental Health of the National Institutes of Health under Award number K23MH094707 (Career Development Award to JWM). Support was also provided by the Iris & Junming Le Foundation (Award to Dr. Murrough), by the Brain and Behavior Research Foundation (NARSAD grant to Dr. Murrough) and by grant UL1TR000067 from the NIH National Center for Advancing Translational Sciences to Mount Sinai. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. NR 80 TC 4 Z9 4 U1 3 U2 7 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0165-0327 EI 1573-2517 J9 J AFFECT DISORDERS JI J. Affect. Disord. PD JAN 15 PY 2016 VL 190 BP 529 EP 536 DI 10.1016/j.jad.2015.10.027 PG 8 WC Clinical Neurology; Psychiatry SC Neurosciences & Neurology; Psychiatry GA CY5QT UT WOS:000366463000076 PM 26571102 ER PT J AU Rodgers, S Vandeleur, CL Ajdacic-Gross, V Aleksandrowicz, AA Strippoli, MPF Castelao, E Glaus, J Lasserre, AM Muller, M Rossler, W Angst, J Preisig, M AF Rodgers, Stephanie Vandeleur, Caroline L. Ajdacic-Gross, Vladeta Aleksandrowicz, Aleksandra A. Strippoli, Marie-Pierre F. Castelao, Enrique Glaus, Jennifer Lasserre, Aurelie M. Mueller, Mario Roessler, Wulf Angst, Jules Preisig, Martin TI Tracing the associations between sex, the atypical and the combined atypical-melancholic depression subtypes: A path analysis SO JOURNAL OF AFFECTIVE DISORDERS LA English DT Article DE Depression; Atypical and melancholic subtypes; Sex; Epidemiology ID PARENTAL BONDING INSTRUMENT; CARDIOVASCULAR RISK-FACTORS; POPULATION-BASED SAMPLE; TEST-RETEST RELIABILITY; GENETIC-STUDIES DIGS; MAJOR DEPRESSION; GENDER-DIFFERENCES; DIAGNOSTIC INTERVIEW; FOLLOW-UP; NEUROVEGETATIVE SYMPTOMS AB Background: Numerous studies have examined determinants leading to preponderance of women in major depressive disorder (MDD), which is particularly accentuated for the atypical depression subtype. It is thus of interest to explore the specific indirect effects influencing the association between sex and established depression subtypes. Methods: The data of 1624 subjects with a lifetime diagnosis of MDD derived from the population-based PsyCoLaus data were used. An atypical (n=256), a melancholic (n=422), a combined atypical and melancholic features subtype (n=198), and an unspecified MDD group (n=748) were constructed according to the DSM-IV specifiers. Path models with direct and indirect effects were applied to the data. Results: Partial mediation of the female-related atypical and combined atypical-melancholic depression subtypes was found. Early anxiety disorders and high emotion-orientated coping acted as mediating variables between sex and the atypical depression subtype. In contrast, high Body Mass Index (BMI) served as a suppression variable, also concerning the association between sex and the combined atypical-melancholic subtype. The latter association was additionally mediated by an early age of MDD onset and early/late anxiety disorders. Limitations: The use of cross-sectional data does not allow causal conclusions. Conclusions: This is the first study that provides evidence for a differentiation of the general mechanisms explaining sex differences of overall MDD by depression subtypes. Determinants affecting the pathways begin early in life. Since some of them are primarily of behavioral nature, the present findings could be a valuable target in mental health care. (C) 2015 Elsevier B.V. All rights reserved. C1 [Rodgers, Stephanie; Ajdacic-Gross, Vladeta; Aleksandrowicz, Aleksandra A.; Mueller, Mario; Roessler, Wulf; Angst, Jules] Univ Zurich, Dept Psychiat Psychotherapy & Psychosomat, Hosp Psychiat, CH-8021 Zurich, Switzerland. [Vandeleur, Caroline L.; Strippoli, Marie-Pierre F.; Castelao, Enrique; Glaus, Jennifer; Lasserre, Aurelie M.; Preisig, Martin] Univ Lausanne Hosp, Psychiat Epidemiol & Psychopathol Res Ctr, Dept Psychiat, Lausanne, Switzerland. [Glaus, Jennifer] NIMH, Genet Epidemiol Res Branch, Intramural Res Program, Bethesda, MD 20892 USA. [Roessler, Wulf] Univ Zurich, Coll Helveticum, CH-8021 Zurich, Switzerland. [Roessler, Wulf] Swiss Fed Inst Technol, Zurich, Switzerland. [Roessler, Wulf] Univ Sao Paulo, Inst Psychiat, Lab Neurosci LIM 27, BR-05508 Sao Paulo, Brazil. RP Rodgers, S (reprint author), Univ Zurich, Dept Psychiat Psychotherapy & Psychosomat, Hosp Psychiat, POB 1930, CH-8021 Zurich, Switzerland. EM stephanie.rodgers@dgsp.uzh.ch RI Strippoli, Marie-Pierre/K-8164-2013; Colaus, PsyColaus/K-6607-2013; Glaus, Jennifer/C-7887-2017; OI Strippoli, Marie-Pierre/0000-0003-3053-484X; Glaus, Jennifer/0000-0001-8883-9473; Castelao, Enrique/0000-0003-1966-3683 FU GlaxoSmithKline; Faculty of Biology and Medicine of Lausanne; Swiss National Science Foundation [3200B0-105993, 3200B0-118308, 33CSCO-122661, 33CS30-139468, 33CS30-148401] FX The CoLauslPsyCoLaus study was and is supported by research grants from GlaxoSmithKline, the Faculty of Biology and Medicine of Lausanne, and the Swiss National Science Foundation (grants 3200B0-105993, 3200B0-118308, 33CSCO-122661, 33CS30-139468 and 33CS30-148401). NR 109 TC 1 Z9 1 U1 3 U2 11 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0165-0327 EI 1573-2517 J9 J AFFECT DISORDERS JI J. Affect. Disord. PD JAN 15 PY 2016 VL 190 BP 807 EP 818 DI 10.1016/j.jad.2015.10.067 PG 12 WC Clinical Neurology; Psychiatry SC Neurosciences & Neurology; Psychiatry GA CY5QT UT WOS:000366463000109 PM 26625093 ER PT J AU Neitzel, RL Heikkinen, MSA Williams, CC Viet, SM Dellarco, M AF Neitzel, Richard L. Heikkinen, Maire S. A. Williams, Christopher C. Viet, Susan Marie Dellarco, Michael TI Pilot study of methods and equipment for in-home noise level measurements SO APPLIED ACOUSTICS LA English DT Article DE Noise; Sound level; Exposure assessment; National Children's Study; mHealth; Smartphone ID ROAD TRAFFIC NOISE; NEW-YORK-CITY; ENVIRONMENTAL NOISE; CONSTRUCTION WORKERS; MENTAL-HEALTH; URBAN NOISE; EXPOSURE; POLLUTION; AIRCRAFT; EUROPE AB Knowledge of the auditory and non-auditory effects of noise has increased dramatically over the past decade, but indoor noise exposure measurement methods have not advanced appreciably, despite the introduction of applicable new technologies. This study evaluated various conventional and smart devices for exposure assessment in the National Children's Study. Three devices were tested: a sound level meter (SLM), a dosimeter, and a smart device with a noise measurement application installed. Instrument performance was evaluated in a series of semi-controlled tests in office environments over 96-h periods, followed by measurements made continuously in two rooms (a child's bedroom and a most used room) in nine participating homes over a 7-day period with subsequent computation of a range of noise metrics. The SLMs and dosimeters yielded similar A-weighted average noise levels. Levels measured by the smart devices often differed substantially (showing both positive and negative bias, depending on the metric) from those measured via SLM and dosimeter, and demonstrated attenuation in some frequency bands in spectral analysis compared to SLM results. Virtually all measurements exceeded the Environmental Protection Agency's 45 dBA-day night limit for indoor residential exposures. The measurement protocol developed here can be employed in homes, demonstrates the possibility of measuring long-term noise exposures in homes with technologies beyond traditional SLMs, and highlights potential pitfalls associated with measurements made by smart devices. (C) 2015 Elsevier Ltd. All rights reserved. C1 [Neitzel, Richard L.] Univ Michigan, Dept Environm Hlth Sci, Ann Arbor, MI 48109 USA. [Neitzel, Richard L.] Univ Michigan, Risk Sci Ctr, Ann Arbor, MI 48109 USA. [Heikkinen, Maire S. A.; Williams, Christopher C.; Viet, Susan Marie] WESTAT Corp, Rockville, MD 20850 USA. [Dellarco, Michael] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Rockville, MD 20852 USA. RP Neitzel, RL (reprint author), Univ Michigan, Dept Environm Hlth Sci, 1415 Washington Hts,SPH 1 6611, Ann Arbor, MI 48109 USA. EM rneitzel@umich.edu OI Neitzel, Richard/0000-0001-5500-2589 FU National Institutes of Health, National Institute of Child Health [GS-23F-8144H, HHSN275201300092U] FX This work was conducted under National Institutes of Health, National Institute of Child Health Contract GS-23F-8144H, Order HHSN275201300092U. The authors wish to thank Abdisalam Khalaf, Pabitra Josse, Shelley Boyd, and Abie Reifer for their assistance in evaluating different devices for potential use in the study, Alexander Koustov and Kan Sun for their assistance with data analysis, and the families who participated in the home monitoring element of the study. NR 45 TC 1 Z9 1 U1 14 U2 36 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0003-682X EI 1872-910X J9 APPL ACOUST JI Appl. Acoust. PD JAN 15 PY 2016 VL 102 BP 1 EP 11 DI 10.1016/j.apacoust.2015.08.018 PG 11 WC Acoustics SC Acoustics GA CV9LO UT WOS:000364608900001 ER PT J AU Vichaya, EG Molkentine, JM Vermeer, DW Walker, AK Feng, R Holder, G Luu, K Mason, RM Saligan, L Heijnen, CJ Kavelaars, A Mason, KA Lee, JH Dantzer, R AF Vichaya, Elisabeth G. Molkentine, Jessica M. Vermeer, Daniel W. Walker, Adam K. Feng, Rebekah Holder, Gerard Luu, Katherine Mason, Ryan M. Saligan, Leo Heijnen, Cobi J. Kavelaars, Annemieke Mason, Kathy A. Lee, John H. Dantzer, Robert TI Sickness behavior induced by cisplatin chemotherapy and radiotherapy in a murine head and neck cancer model is associated with altered mitochondrial gene expression SO BEHAVIOURAL BRAIN RESEARCH LA English DT Article DE Cancer; Human papilloma virus; Sickness behavior; Chemoradiotherapy; Hypoxia; Mitochondria ID SQUAMOUS-CELL CARCINOMA; QUALITY-OF-LIFE; HUMAN-PAPILLOMAVIRUS; BREAST-CANCER; MOUSE MODEL; INFLAMMATORY CYTOKINES; CHEMORADIATION THERAPY; OROPHARYNGEAL CANCER; INVASIVE GROWTH; INDUCED FATIGUE AB The present study was undertaken to explore the possible mechanisms of the behavioral alterations that develop in response to cancer and to cancer therapy. For this purpose we used a syngeneic heterotopic mouse model of human papilloma virus (HPV)-related head and neck cancer in which cancer therapy is curative. Mice implanted or not with HPV+ tumor cells were exposed to sham treatment or a regimen of cisplatin and radiotherapy (chemoradiation). Sickness was measured by body weight loss and reduced food intake. Motivation was measured by burrowing, a highly prevalent species specific behavior. Tumor-bearing mice showed a gradual decrease in burrowing over time and increased brain and liver inflammatory cytokine mRNA expression by 28 days post tumor implantation. Chemoradiation administered to healthy mice resulted in a mild decrease in burrowing, body weight, and food intake. Chemoradiation in tumor-bearing mice decreased tumor growth and abrogated liver and brain inflammation, but failed to attenuate burrowing deficits. PCR array analysis of selected hypoxia and mitochondrial genes revealed that both the tumor and chemoradiation altered the expression of genes involved in mitochondrial energy metabolism within the liver and brain and increased expression of genes related to HIF-1 alpha signaling within the brain. The most prominent changes in brain mitochondrial genes were noted in tumor-bearing mice treated with chemoradiation. These findings indicate that targeting mitochondrial dysfunction following cancer and cancer therapy may be a strategy for prevention of cancer-related symptoms. (C) 2015 Elsevier B.V. All rights reserved. C1 [Vichaya, Elisabeth G.; Walker, Adam K.; Luu, Katherine; Heijnen, Cobi J.; Kavelaars, Annemieke; Dantzer, Robert] Univ Texas MD Anderson Canc Ctr, Dept Symptom Res, Houston, TX 77030 USA. [Molkentine, Jessica M.; Mason, Ryan M.; Mason, Kathy A.] Univ Texas MD Anderson Canc Ctr, Dept Expt Radiat Oncol, Houston, TX 77030 USA. [Vermeer, Daniel W.; Lee, John H.] Sanford Res, Canc Biol Res Ctr, Sioux Falls, SD 57104 USA. [Feng, Rebekah; Holder, Gerard; Saligan, Leo] NINR, Bethesda, MD 20892 USA. RP Vichaya, EG (reprint author), Univ Texas MD Anderson Canc Ctr, Dept Symptom Res, 1515 Holcombe Blvd,Unit 384, Houston, TX 77030 USA. EM egvichaya@mdanderson.org OI Vichaya, Elisabeth/0000-0001-9421-7419; Dantzer, Robert/0000-0001-9399-6107 FU National Cancer Institute of the National Institutes of Health [R01CA193522]; University of Texas MD Anderson Cancer Center; National Institutes of Health MD Anderson Cancer Center Support Grant [CA016672] FX The work reported in this publication was supported the National Cancer Institute of the National Institutes of Health (R01CA193522). Additional support came from the University of Texas MD Anderson Cancer Center and the National Institutes of Health MD Anderson Cancer Center Support Grant (CA016672). The content is solely the responsibility of the authors and does not necessarily represent the official views of the funding sources. In addition, we would like to thank Devdeep Chandra and Myrna Garcia for their assistance with data collection. NR 68 TC 2 Z9 2 U1 0 U2 6 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0166-4328 EI 1872-7549 J9 BEHAV BRAIN RES JI Behav. Brain Res. PD JAN 15 PY 2016 VL 297 BP 241 EP 250 DI 10.1016/j.bbr.2015.10.024 PG 10 WC Behavioral Sciences; Neurosciences SC Behavioral Sciences; Neurosciences & Neurology GA CZ4YB UT WOS:000367107900030 PM 26475509 ER PT J AU Eavani, H Hsieh, MK An, Y Erus, G Beason-Held, L Resnick, S Davatzikos, C AF Eavani, Harini Hsieh, Meng Kang An, Yang Erus, Guray Beason-Held, Lori Resnick, Susan Davatzikos, Christos TI Capturing heterogeneous group differences using mixture-of-experts: Application to a study of aging SO NEUROIMAGE LA English DT Article DE Heterogeneity; Mixture of experts; Support vector machines ID MILD COGNITIVE IMPAIRMENT; RESTING-STATE FMRI; FUZZY PARTITIONS; SUBJECT MOTION; OLDER-ADULTS; CLASSIFICATION; PATTERNS; DECLINE; MEMORY; NETWORKS AB In MRI studies, linear multi-variate methods are often employed to identify regions or connections that are affected due to disease or normal aging. Such linear models inherently assume that there is a single, homogeneous abnormality pattern that is present in all affected individuals. While kernel-based methods can implicitly model a non-linear effect, and therefore the heterogeneity in the affected group, extracting and interpreting information about affected regions is difficult. In this paper, we present a method that explicitly models and captures heterogeneous patterns of change in the affected group relative to a reference group of controls. For this purpose, we use the Mixture-of-Experts (MOE) framework, which combines unsupervised modeling of mixtures of distributions with supervised learning of classifiers. MOE approximates the non-linear boundary between the two groups with a piece-wise linear boundary, thus allowing discovery of multiple patterns of group differences. In the case of patient/control comparisons, each such pattern aims to capture a different dimension of a disease, and hence to identify patient subgroups. We validated our model using multiple simulation scenarios and performance measures. We applied this method to resting state functional MRI data from the Baltimore Longitudinal Study of Aging, to investigate heterogeneous effects of aging on brain function in cognitively normal older adults (>85 years) relative to a reference group of normal young to middle-aged adults (<60 years). We found strong evidence for the presence of two subgroups of older adults, with similar age distributions in each subgroup, but different connectivity patterns associated with aging. While both older subgroups showed reduced functional connectivity in the Default Mode Network (DMN), increases in functional connectivity within the pre-frontal cortex as well as the bilateral insula were observed only for one of the two subgroups. Interestingly, the subgroup showing this increased connectivity (unlike the other subgroup) was, cognitively similar at baseline to the young and middle-aged subjects in two of seven cognitive domains, and had a faster rate of cognitive decline in one of seven domains. These results suggest that older individuals whose baseline cognitive performance is comparable to that of younger individuals recruit their "cognitive reserve" later in life, to compensate for reduced connectivity in other brain regions. (C) 2015 Elsevier Inc. All rights reserved. C1 [Eavani, Harini; Hsieh, Meng Kang; Erus, Guray; Davatzikos, Christos] Univ Penn, Ctr Biomed Image Comp & Analyt, Philadelphia, PA 19104 USA. [An, Yang; Beason-Held, Lori; Resnick, Susan] NIA, Baltimore, MD 21224 USA. RP Eavani, H (reprint author), Univ Penn, Ctr Biomed Image Comp & Analyt, Philadelphia, PA 19104 USA. EM Harini.Eavani@uphs.upenn.edu FU NIH [AG014971, HHSN2712013000284P]; Intramural Research Program, National Institute on Aging; NIA FX This study was supported in part by NIH grant AG014971, the Intramural Research Program, National Institute on Aging, and NIH contract HHSN2712013000284P by the NIA to UPenn. We would also like to thank our anonymous reviewers whose helpful suggestions have greatly improved this manuscript. NR 44 TC 2 Z9 2 U1 1 U2 3 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1053-8119 EI 1095-9572 J9 NEUROIMAGE JI Neuroimage PD JAN 15 PY 2016 VL 125 BP 498 EP 514 DI 10.1016/j.neuroimage.2015.10.045 PG 17 WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA CY8GT UT WOS:000366647500045 PM 26525656 ER PT J AU Huber, L Ivanov, D Guidi, M Turner, R Uludag, K Moller, HE Poser, BA AF Huber, Laurentius Ivanov, Dimo Guidi, Maria Turner, Robert Uludag, Kamil Moeller, Harald E. Poser, Benedikt A. TI Functional cerebral blood volume mapping with simultaneous multi-slice acquisition SO NEUROIMAGE LA English DT Article DE Vascular space occupancy; SS-SI VASO; cerebral blood volume; Simultaneous multi-slice; Multi-band; 7 Tesla MRI ID VASCULAR-SPACE-OCCUPANCY; MAGNETIZATION TRANSFER CONTRAST; NEGATIVE BOLD RESPONSES; GRADIENT-ECHO FMRI; WHOLE-BRAIN; SPIN-ECHO; 7 T; RESOLUTION FMRI; MOTOR CORTEX; VENOUS-BLOOD AB The aim of this study is to overcome the current limits of brain coverage available with multi-slice echo planar imaging (EPI) for vascular space occupancy (VASO) mapping. By incorporating simultaneous multi-slice (SMS) EPI image acquisition into slice-saturation slab-inversion VASO (SS-SI VASO), many more slices can be acquired for non-invasive functional measurements of blood volume responses. Blood-volume-weighted VASO and gradient echo blood oxygenation level-dependent (GE-BOLD) data were acquired in humans at 7 T with a 32-channel head coil. SMS-VASO was applied in three scenarios: A) high-resolution acquisition of spatially distant brain areas in the visuo-motor network (V1/V5/M1/S1); B) high-resolution acquisition of an imaging slab covering the entire M1/S1 hand regions; and C) low-resolution acquisition with near whole-brain coverage. The results show that the SMS-VASO sequence provided images enabling robust detection of blood volume changes in up to 20 slices with signal readout durations shorter than 150 ms. High-resolution application of SMS-VASO revealed improved specificity of VASO to GM tissue without contamination from large draining veins compared to GE-BOLD in the visual cortex and in the sensory-motor cortex. It is concluded that VASO fMRI with SMS-EPI allows obtaining a reasonable three-dimensional coverage not achievable with standard VASO during the short time period when blood magnetization is approximately nulled. Due to the increased brain coverage and better spatial specificity to GM tissue of VASO compared to GE-BOLD signal, the proposed method may play an important role in high-resolution human fMRI at 7 T. (C) 2015 Elsevier Inc. All rights reserved. C1 [Huber, Laurentius; Guidi, Maria; Turner, Robert; Moeller, Harald E.] Max Planck Inst Human Cognit & Brain Sci, Leipzig, Germany. [Huber, Laurentius] NIMH, Sect Funct Imaging Methods, NIH, Bethesda, MD 20892 USA. [Ivanov, Dimo; Uludag, Kamil; Poser, Benedikt A.] Maastricht Univ, Maastricht Brain Imaging Ctr, NL-6200 MD Maastricht, Netherlands. RP Huber, L (reprint author), NIMH, Sect Funct Imaging Methods, NIH, Bldg 10,Room 1D80B,10 Ctr Dr,MSC 1148, Bethesda, MD 20892 USA. EM Laurentius.Huber@nih.gov RI Moller, Harald/A-1565-2008; OI Moller, Harald/0000-0002-5659-1925; Turner, Robert/0000-0001-5055-9644; Poser, Benedikt A/0000-0001-8190-4367 FU Max Planck Society; Netherlands Organization for Scientific Research NWO [VIDI 452-11-002]; Initial Training Network, HiMR - FP7 Marie Curie Actions of the European Commission [FP7-PEOPLE-2012-ITN-316716] FX We thank Domenica Wilfling and Elisabeth Wladimirow for radiographic assistance. We thank Steve Cauley at MGH for sharing the interface of their image reconstruction for use with our SMS-VASO sequence. The research was supported by the Max Planck Society and Netherlands Organization for Scientific Research NWO: VIDI 452-11-002 to Kamil Uludag. Maria Guidi was supported by the Initial Training Network, HiMR, funded by the FP7 Marie Curie Actions of the European Commission (FP7-PEOPLE-2012-ITN-316716). Preliminary accounts of this work have been presented in the Proceedings of the 23th Annual Meeting of ISMRM, Toronto, Canada, 2015 (abstract 600). NR 56 TC 2 Z9 2 U1 1 U2 7 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1053-8119 EI 1095-9572 J9 NEUROIMAGE JI Neuroimage PD JAN 15 PY 2016 VL 125 BP 1159 EP 1168 DI 10.1016/j.neuroimage.2015.10.082 PG 10 WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA CY8GT UT WOS:000366647500108 PM 26522423 ER PT J AU Guy, JR Sati, P Leibovitch, E Jacobson, S Silva, AC Reich, DS AF Guy, Joseph R. Sati, Pascal Leibovitch, Emily Jacobson, Steven Silva, Afonso C. Reich, Daniel S. TI Custom fit 3D-printed brain holders for comparison of histology with MRI in marmosets SO JOURNAL OF NEUROSCIENCE METHODS LA English DT Article DE MRI; Ex vivo; Histology; 3D printing; Marmoset; EAE ID MULTIPLE-SCLEROSIS; COMMON MARMOSET; RECONSTRUCTION; STATISTICS; ALIGNMENT; SECTIONS; LESIONS; VOLUME; MODEL; EAE AB Background: MRI has the advantage of sampling large areas of tissue and locating areas of interest in 3D space in both living and ex vivo systems, whereas histology has the ability to examine thin slices of ex vivo tissue with high detail and specificity. Although both are valuable tools, it is currently difficult to make high-precision comparisons between MRI and histology due to large differences inherent to the techniques. A method combining the advantages would be an asset to understanding the pathological correlates of MRI. New method: 3D-printed brain holders were used to maintain marmoset brains in the same orientation during acquisition of ex vivo MRI and pathologic cutting of the tissue. Results: The results of maintaining this same orientation show that sub-millimeter, discrete neuropathological features in marmoset brain consistently share size, shape, and location between histology and ex vivo MRI, which facilitates comparison with serial imaging acquired in vivo. Comparison with existing methods: Existing methods use computational approaches sensitive to data input in order to warp histologic images to match large-scale features on MRI, but the new method requires no warping of images, due to a preregistration accomplished in the technique, and is insensitive to data formatting and artifacts in both MRI and histology. Conclusions: The simple method of using 3D-printed brain holders to match brain orientation during pathologic sectioning and MRI acquisition enables rapid and precise comparison of small features seen on MRI to their underlying histology. Published by Elsevier B.V. C1 [Guy, Joseph R.; Sati, Pascal; Leibovitch, Emily; Jacobson, Steven; Reich, Daniel S.] NINDS, Div Neuroimmunol & Neurovirol, Bethesda, MD 20892 USA. [Silva, Afonso C.] NINDS, Lab Funct & Mol Imaging, Bethesda, MD 20892 USA. RP Reich, DS (reprint author), NINDS, Div Neuroimmunol & Neurovirol, 10 Ctr Dr MSC 1400,Bldg 10 Room 5C103, Bethesda, MD 20892 USA. EM joseph.guy@nih.gov; pascal.sati@nih.gov; leibovitchel@ninds.nih.gov; JacobsonS@ninds.nih.gov; SilvaA@ninds.nih.gov; reichds@ninds.nih.gov RI Reich, Daniel/E-5701-2010 OI Reich, Daniel/0000-0002-2628-4334 FU Intramural Research Program of the National Institute of Neurological Disorders and Stroke [Z01 NS003119] FX We thank the Section on Instrumentation Core Facility at the NIH for assistance with 3D printing and troubleshooting of numerous brain slicer prototypes. We also thank Dr. Alfredo Molinolo for assistance in developing the histology staining protocol to suit our needs. This research was funded by the Intramural Research Program of the National Institute of Neurological Disorders and Stroke (grant number Z01 NS003119). NR 18 TC 3 Z9 3 U1 3 U2 27 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0165-0270 EI 1872-678X J9 J NEUROSCI METH JI J. Neurosci. Methods PD JAN 15 PY 2016 VL 257 BP 55 EP 63 DI 10.1016/j.jneumeth.2015.09.002 PG 9 WC Biochemical Research Methods; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA CY2FL UT WOS:000366224100007 PM 26365332 ER PT J AU Schleicher, RI Reichenbach, F Kraft, P Kumar, A Lescan, M Todt, F Gobel, K Hilgendorf, I Geisler, T Bauer, A Olbrich, M Schaller, M Wesselborg, S O'Reilly, L Meuth, SG Schulze-Osthoff, K Gawaz, M Li, XR Kleinschnitz, C Edlich, F Langer, HF AF Schleicher, Rebecca I. Reichenbach, Frank Kraft, Peter Kumar, Anil Lescan, Mario Todt, Franziska Goebel, Kerstin Hilgendorf, Ingo Geisler, Tobias Bauer, Axel Olbrich, Marcus Schaller, Martin Wesselborg, Sebastian O'Reilly, Lorraine Meuth, Sven G. Schulze-Osthoff, Klaus Gawaz, Meinrad Li, Xuri Kleinschnitz, Christoph Edlich, Frank Langer, Harald F. TI Platelets induce apoptosis via membrane-bound FasL (vol 126, pg 1483, 2015) SO BLOOD LA English DT Correction C1 [Schleicher, Rebecca I.; Olbrich, Marcus; Langer, Harald F.] Univ Tubingen, Dept Cardiovasc Med, Sect Cardioimmunol, Tubingen, Germany. [Schleicher, Rebecca I.; Geisler, Tobias; Bauer, Axel; Olbrich, Marcus; Gawaz, Meinrad; Langer, Harald F.] Univ Tubingen, Dept Cardiovasc Med, Univ Hosp, Tubingen, Germany. [Reichenbach, Frank; Todt, Franziska; Edlich, Frank] Univ Freiburg, Inst Biochem & Mol Biol, Ctr Biochem & Mol Cell Res ZBMZ, Hugstetter Str 55, D-79106 Freiburg, Germany. [Reichenbach, Frank] Univ Freiburg, Fac Biol, Hugstetter Str 55, D-79106 Freiburg, Germany. [Reichenbach, Frank] Univ Freiburg, Spemann Grad Sch Biol & Med, Hugstetter Str 55, D-79106 Freiburg, Germany. [Kraft, Peter; Kleinschnitz, Christoph] Univ Hosp Wuerzburg, Dept Neurol, Wurzburg, Germany. [Kumar, Anil] NEI, Bethesda, MD 20892 USA. [Lescan, Mario] Eberhard Karls Univ Tubingen, Dept Cardiovasc Surg, Univ Hosp, Tubingen, Germany. [Goebel, Kerstin; Meuth, Sven G.] Univ Munster, Dept Neurol, Munster, Germany. [Goebel, Kerstin; Meuth, Sven G.] Univ Munster, Inst Physiol Neuropathophysiol, Munster, Germany. [Hilgendorf, Ingo] Univ Freiburg, Dept Cardiol & Angiol 1, Ctr Heart, Hugstetter Str 55, D-79106 Freiburg, Germany. [Schaller, Martin] Univ Tubingen, Dept Dermatol, Univ Hosp, Tubingen, Germany. [Wesselborg, Sebastian] Univ Dusseldorf, Inst Mol Med, Dusseldorf, Germany. [O'Reilly, Lorraine] Royal Melbourne Hosp, Walter & Eliza Hall Inst Med Res, Parkville, Vic 3050, Australia. [Schulze-Osthoff, Klaus] Univ Tubingen, Interfac Inst Biochem, Tubingen, Germany. [Schulze-Osthoff, Klaus] German Canc Consortium, Heidelberg, Germany. [Schulze-Osthoff, Klaus] German Canc Res Ctr, Heidelberg, Germany. [Li, Xuri] Sun Yat Sen Univ, State Key Lab Ophthalmol, Zhongshan Ophthalm Ctr, Guangzhou 510275, Guangdong, Peoples R China. [Edlich, Frank] Univ Freiburg, BIOSS Ctr Biol Signalling Studies, Hugstetter Str 55, D-79106 Freiburg, Germany. RP Schleicher, RI (reprint author), Univ Tubingen, Dept Cardiovasc Med, Sect Cardioimmunol, Tubingen, Germany. NR 1 TC 0 Z9 0 U1 2 U2 5 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 2021 L ST NW, SUITE 900, WASHINGTON, DC 20036 USA SN 0006-4971 EI 1528-0020 J9 BLOOD JI Blood PD JAN 14 PY 2016 VL 127 IS 2 BP 270 EP 270 DI 10.1182/blood-2015-11-682914 PG 1 WC Hematology SC Hematology GA DC5UG UT WOS:000369285400019 ER PT J AU Medellin, DC Zhou, Q Scott, R Hill, RM Frail, SK Dasari, R Ontiveros, SJ Pelly, SC van Otterlo, WAL Betancourt, T Shuster, CB Hamel, E Bai, RL LaBarbera, DV Rogelj, S Frolova, LV Kornienko, A AF Medellin, Derek C. Zhou, Qiong Scott, Robert Hill, R. Matthew Frail, Sarah K. Dasari, Ramesh Ontiveros, Steven J. Pelly, Stephen C. van Otterlo, Willem A. L. Betancourt, Tania Shuster, Charles B. Hamel, Ernest Bai, Ruoli LaBarbera, Daniel V. Rogelj, Snezna Frolova, Liliya V. Kornienko, Alexander TI Novel Microtubule-Targeting 7-Deazahypoxanthines Derived from Marine Alkaloid Rigidins with Potent in Vitro and in Vivo Anticancer Activities SO JOURNAL OF MEDICINAL CHEMISTRY LA English DT Article ID NATURAL-PRODUCTS; TUBULIN; COLCHICINE AB Docking studies of tubulin-targeting C2-substituted 7-deazahypoxanthine analogues of marine alkaloid rigidins led to the design and synthesis of compounds containing linear C2-substituents. The C2-alkynyl analogue was found to have double- to single-digit nanomolar antiproliferative IC50 values and showed statistically significant tumor size reduction in a colon cancer mouse model at nontoxic concentrations. These results provide impetus and further guidance for the development of these rigidin analogues as anticancer agents. C1 [Medellin, Derek C.; Scott, Robert; Hill, R. Matthew; Dasari, Ramesh; Betancourt, Tania; Kornienko, Alexander] Texas State Univ, Dept Chem & Biochem, San Marcos, TX 78666 USA. [Zhou, Qiong; LaBarbera, Daniel V.] Univ Colorado Anschutz Med Campus, Dept Pharmaceut Sci, Skaggs Sch Pharm & Pharmaceut Sci, Aurora, CO 80045 USA. [Frail, Sarah K.; Rogelj, Snezna; Frolova, Liliya V.] New Mexico Inst Min & Technol, Dept Chem, Socorro, NM 87801 USA. [Frail, Sarah K.; Rogelj, Snezna; Frolova, Liliya V.] New Mexico Inst Min & Technol, Dept Biol, Socorro, NM 87801 USA. [Ontiveros, Steven J.; Shuster, Charles B.] New Mexico State Univ, Dept Biol, Las Cruces, NM 88003 USA. [Pelly, Stephen C.; van Otterlo, Willem A. L.] Univ Stellenbosch, Dept Chem & Polymer Sci, ZA-7600 Stellenbosch, Western Cape, South Africa. [Betancourt, Tania] Texas State Univ, Mat Sci Engn & Commercializat Program, San Marcos, TX 78666 USA. [Hamel, Ernest; Bai, Ruoli] NCI, Screening Technol Branch, Dev Therapeut Program, Frederick Natl Lab Canc Res,NIH, Frederick, MD 21702 USA. RP Kornienko, A (reprint author), Texas State Univ, Dept Chem & Biochem, San Marcos, TX 78666 USA.; Frolova, LV (reprint author), New Mexico Inst Min & Technol, Dept Chem, Socorro, NM 87801 USA.; Frolova, LV (reprint author), New Mexico Inst Min & Technol, Dept Biol, Socorro, NM 87801 USA. EM lfrolova@nmt.edu; a_k76@txstate.edu FU National Cancer Institute [CA186046-01A1]; National Institute of General Medical Sciences [P20GM103451]; Welch Foundation [AI-0045]; National Science Foundation (NSF) [0946998]; Texas Emerging Technology Fund; Department of Defense Peer Review Cancer Research Program Grant [W81XWH-13-1-0344]; [5SC1HD063917] FX This project was supported by grants from the National Cancer Institute (Grant CA186046-01A1), National Institute of General Medical Sciences (Grant P20GM103451), Welch Foundation (Grant AI-0045), National Science Foundation (NSF Award 0946998), and the Texas Emerging Technology Fund. C.B.S. and S.J.O. were supported by Grant 5SC1HD063917. D.V.L. and Q.Z. were supported by Department of Defense Peer Review Cancer Research Program Grant W81XWH-13-1-0344. W.A.L.v.O. and S.C.P. thank the CHPC (Centre for High Performance Computing, South Africa) for access to Accelrys Discovery Studio. S.R. and L.V.F. acknowledge their NMT Presidential Research Support. L.V.F. acknowledges Alex Pendleton. The content of this paper is solely the responsibility of the authors and does not necessarily reflect the official views of the National Institutes of Health. NR 11 TC 2 Z9 2 U1 5 U2 16 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 JAN 14 PY 2016 VL 59 IS 1 BP 480 EP 485 DI 10.1021/acs.jmedchem.5b01426 PG 6 WC Chemistry, Medicinal SC Pharmacology & Pharmacy GA DB5OV UT WOS:000368564400034 PM 26641132 ER PT J AU Inge, TH Courcoulas, AP Jenkins, TM Michalsky, MP Helmrath, MA Brandt, ML Harmon, CM Zeller, MH Chen, MK Xanthakos, SA Horlick, M Buncher, CR AF Inge, Thomas H. Courcoulas, Anita P. Jenkins, Todd M. Michalsky, Marc P. Helmrath, Michael A. Brandt, Mary L. Harmon, Carroll M. Zeller, Meg H. Chen, Mike K. Xanthakos, Stavra A. Horlick, Mary Buncher, C. Ralph CA Teen-LABS Consortium TI Weight Loss and Health Status 3 Years after Bariatric Surgery in Adolescents SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Article ID MORBIDLY OBESE ADOLESCENTS; GASTRIC BYPASS-SURGERY; QUALITY-OF-LIFE; CHILDREN; OUTCOMES; METAANALYSIS; PREVALENCE; TRENDS; RISK AB BACKGROUND Bariatric surgery is increasingly considered for the treatment of adolescents with severe obesity, but few prospective adolescent-specific studies examining the efficacy and safety of weight-loss surgery are available to support clinical decision making. METHODS We prospectively enrolled 242 adolescents undergoing weight-loss surgery at five U.S. centers. Patients undergoing Roux-en-Y gastric bypass (161 participants) or sleeve gastrectomy (67) were included in the analysis. Changes in body weight, coexisting conditions, cardiometabolic risk factors, and weight-related quality of life and postoperative complications were evaluated through 3 years after the procedure. RESULTS The mean (+/- SD) baseline age of the participants was 17 +/- 1.6 years, and the mean body-mass index (the weight in kilograms divided by the square of the height in meters) was 53; 75% of the participants were female, and 72% were white. At 3 years after the procedure, the mean weight had decreased by 27% (95% confidence interval [CI], 25 to 29) in the total cohort, by 28% (95% CI, 25 to 30) among participants who underwent gastric bypass, and by 26% (95% CI, 22 to 30) among those who underwent sleeve gastrectomy. By 3 years after the procedure, remission of type 2 diabetes occurred in 95% (95% CI, 85 to 100) of participants who had had the condition at baseline, remission of abnormal kidney function occurred in 86% (95% CI, 72 to 100), remission of prediabetes in 76% (95% CI, 56 to 97), remission of elevated blood pressure in 74% (95% CI, 64 to 84), and remission of dyslipidemia in 66% (95% CI, 57 to 74). Weight-related quality of life also improved significantly. However, at 3 years after the bariatric procedure, hypoferritinemia was found in 57% (95% CI, 50 to 65) of the participants, and 13% (95% CI, 9 to 18) of the participants had undergone one or more additional intraabdominal procedures. CONCLUSIONS In this multicenter, prospective study of bariatric surgery in adolescents, we found significant improvements in weight, cardiometabolic health, and weight-related quality of life at 3 years after the procedure. Risks associated with surgery included specific micronutrient deficiencies and the need for additional abdominal procedures. (Funded by the National Institute of Diabetes and Digestive and Kidney Diseases and others; Teen-LABS ClinicalTrials.gov number, NCT00474318.) C1 [Inge, Thomas H.; Jenkins, Todd M.; Helmrath, Michael A.; Zeller, Meg H.; Xanthakos, Stavra A.] Cincinnati Childrens Hosp Med Ctr, Cincinnati, OH 45229 USA. [Buncher, C. Ralph] Univ Cincinnati, Cincinnati, OH 45221 USA. [Michalsky, Marc P.] Nationwide Childrens Hosp, Columbus, OH USA. [Courcoulas, Anita P.] Univ Pittsburgh, Med Ctr, Pittsburgh, PA USA. [Brandt, Mary L.] Texas Childrens Hosp, Baylor Coll Med, Houston, TX 77030 USA. [Harmon, Carroll M.] Univ Buffalo, Women & Childrens Hosp, Buffalo, NY USA. [Chen, Mike K.] Univ Alabama Birmingham, Birmingham, AL USA. [Horlick, Mary] NIDDKD, Bethesda, MD USA. RP Inge, TH (reprint author), Cincinnati Childrens Hosp Med Ctr, 3333 Burnet Ave,MLC 2023, Cincinnati, OH 45229 USA. OI michalsky, marc/0000-0002-7119-3634 FU National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health [U01DK072493, UM1DK072493, UM1DK095710, UL1TR000077-04, UL1RR025755, M01-RR00188, UL1RR024153, UL1TR000005, UL1TR000165] FX Supported by grants from the National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health (U01DK072493 and UM1DK072493 to Dr. Inge, UM1DK095710 to Dr. Buncher, UL1TR000077-04 to Cincinnati Children's Hospital Medical Center, UL1RR025755 to Nationwide Children's Hospital, M01-RR00188 to Texas Children's Hospital/Baylor College of Medicine, UL1RR024153 and UL1TR000005 to the University of Pittsburgh, and UL1TR000165 to the University of Alabama, Birmingham). NR 25 TC 50 Z9 50 U1 9 U2 16 PU MASSACHUSETTS MEDICAL SOC PI WALTHAM PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA SN 0028-4793 EI 1533-4406 J9 NEW ENGL J MED JI N. Engl. J. Med. PD JAN 14 PY 2016 VL 374 IS 2 BP 113 EP 123 DI 10.1056/NEJMoa1506699 PG 11 WC Medicine, General & Internal SC General & Internal Medicine GA DA7PQ UT WOS:000367996700006 PM 26544725 ER PT J AU Linehan, WM Spellman, PT Ricketts, CJ Creighton, CJ Fei, SS Davis, C Wheeler, DA Murray, BA Schmidt, L Vocke, CD Peto, M Al Mamun, AAM Shinbrot, E Sethi, A Brooks, S Rathmell, WK Brooks, AN Hoadley, KA Robertson, AG Brooks, D Bowlby, R Sadeghi, S Shen, H Weisenberger, DJ Bootwalla, M Baylin, SB Laird, PW Cherniack, AD Saksena, G Haake, S Li, J Liang, H Lu, YL Mills, GB Akbani, R Leiserson, MDM Raphael, BJ Anur, P Bottaro, D Albiges, L Barnabas, N Choueiri, TK Czerniak, B Godwin, AK Hakimi, AA Ho, TH Hsieh, J Ittmann, M Kim, WY Krishnan, B Merino, MJ Shaw, KRM Reuter, VE Reznik, E Shelley, CS Shuch, B Signoretti, S Srinivasan, R Tamboli, P Thomas, G Tickoo, S Burnett, K Crain, D Gardner, J Lau, K Mallery, D Morris, S Paulauskis, JD Penny, RJ Shelton, C Shelton, WT Sherman, M Thompson, E Yena, P Avedon, MT Bowen, J Gastier-Foster, JM Gerken, M Leraas, KM Lichtenberg, TM Ramirez, NC Santos, T Wise, L Zmuda, E Demchok, JA Felau, I Hutter, CM Sheth, M Sofia, HJ Tarnuzzer, R Wang, ZN Yang, LM Zenklusen, JC Zhang, JS Ayala, B Baboud, J Chudamani, S Liu, J Lolla, L Naresh, R Pihl, T Sun, Q Wan, YH Wu, Y Ally, A Balasundaram, M Balu, S Beroukhim, R Bodenheimer, T Buhay, C Butterfield, YSN Carlsen, R Carter, SL Chao, H Chuah, E Clarke, A Covington, KR Dahdouli, M Dewal, N Dhalla, N Doddapaneni, HV Drummond, JA Gabriel, SB Gibbs, RA Guin, R Hale, W Hawes, A Hayes, DN Holt, RA Hoyle, AP Jefferys, SR Jones, SJM Jones, CD Kalra, D Kovar, C Lewis, L Li, J Ma, Y Marra, MA Mayo, M Meng, SW Meyerson, M Mieczkowski, PA Moore, RA Morton, D Mose, LE Mungall, AJ Muzny, D Parker, JS Perou, CM Roach, J Schein, JE Schumacher, SE Shi, Y Simons, JV Sipahimalani, P Skelly, T Soloway, MG Sougnez, C Tam, A Tan, D Thiessen, N Veluvolu, U Wang, M Wilkerson, MD Wong, T Wu, JY Xi, L Zhou, J Bedford, J Chen, FJ Fu, Y Gerstein, M Haussler, D Kasaian, K Lai, P Ling, SY Radenbaugh, A Van Den Berg, D Weinstein, JN Zhu, JC Albert, M Alexopoulou, I Andersen, JJ Auman, JT Bartlett, J Bastacky, S Bergsten, J Blute, ML Boice, L Bollag, RJ Boyd, J Castle, E Chen, YB Cheville, JC Curley, E Davies, B DeVolk, A Dhir, R Dike, L Eckman, J Engel, J Harr, J Hrebinko, R Huang, M Huelsenbeck-Dill, L Iacocca, M Jacobs, B Lobis, M Maranchie, JK McMeekin, S Myers, J Nelson, J Parfitt, J Parwani, A Petrelli, N Rabeno, B Roy, S Salner, AL Slaton, J Stanton, M Thompson, RH Thorne, L Tucker, K Weinberger, PM Winemiller, C Zach, LA Zuna, R AF Linehan, W. Marston Spellman, Paul T. Ricketts, Christopher J. Creighton, Chad J. Fei, Suzanne S. Davis, Caleb Wheeler, David A. Murray, Bradley A. Schmidt, Laura Vocke, Cathy D. Peto, Myron Al Mamun, Abu Amar M. Shinbrot, Eve Sethi, Anurag Brooks, Samira Rathmell, W. Kimryn Brooks, Angela N. Hoadley, Katherine A. Robertson, A. Gordon Brooks, Denise Bowlby, Reanne Sadeghi, Sara Shen, Hui Weisenberger, Daniel J. Bootwalla, Moiz Baylin, Stephen B. Laird, Peter W. Cherniack, Andrew D. Saksena, Gordon Haake, Scott Li, Jun Liang, Han Lu, Yiling Mills, Gordon B. Akbani, Rehan Leiserson, Mark D. M. Raphael, Benjamin J. Anur, Pavana Bottaro, Donald Albiges, Laurence Barnabas, Nandita Choueiri, Toni K. Czerniak, Bogdan Godwin, Andrew K. Hakimi, A. Ari Ho, Thai H. Hsieh, James Ittmann, Michael Kim, William Y. Krishnan, Bhavani Merino, Maria J. Shaw, Kenna R. Mills Reuter, Victor E. Reznik, Ed Shelley, Carl S. Shuch, Brian Signoretti, Sabina Srinivasan, Ramaprasad Tamboli, Pheroze Thomas, George Tickoo, Satish Burnett, Kenneth Crain, Daniel Gardner, Johanna Lau, Kevin Mallery, David Morris, Scott Paulauskis, Joseph D. Penny, Robert J. Shelton, Candace Shelton, W. Troy Sherman, Mark Thompson, Eric Yena, Peggy Avedon, Melissa T. Bowen, Jay Gastier-Foster, Julie M. Gerken, Mark Leraas, Kristen M. Lichtenberg, Tara M. Ramirez, Nilsa C. Santos, Tracie Wise, Lisa Zmuda, Erik Demchok, John A. Felau, Ina Hutter, Carolyn M. Sheth, Margi Sofia, Heidi J. Tarnuzzer, Roy Wang, Zhining Yang, Liming Zenklusen, Jean C. Zhang, Jiashan Ayala, Brenda Baboud, Julien Chudamani, Sudha Liu, Jia Lolla, Laxmi Naresh, Rashi Pihl, Todd Sun, Qiang Wan, Yunhu Wu, Ye Ally, Adrian Balasundaram, Miruna Balu, Saianand Beroukhim, Rameen Bodenheimer, Tom Buhay, Christian Butterfield, Yaron S. N. Carlsen, Rebecca Carter, Scott L. Chao, Hsu Chuah, Eric Clarke, Amanda Covington, Kyle R. Dahdouli, Mahmoud Dewal, Ninad Dhalla, Noreen Doddapaneni, Harsha V. Drummond, Jennifer A. Gabriel, Stacey B. Gibbs, Richard A. Guin, Ranabir Hale, Walker Hawes, Alicia Hayes, D. Neil Holt, Robert A. Hoyle, Alan P. Jefferys, Stuart R. Jones, Steven J. M. Jones, Corbin D. Kalra, Divya Kovar, Christie Lewis, Lora Li, Jie Ma, Yussanne Marra, Marco A. Mayo, Michael Meng, Shaowu Meyerson, Matthew Mieczkowski, Piotr A. Moore, Richard A. Morton, Donna Mose, Lisle E. Mungall, Andrew J. Muzny, Donna Parker, Joel S. Perou, Charles M. Roach, Jeffrey Schein, Jacqueline E. Schumacher, Steven E. Shi, Yan Simons, Janae V. Sipahimalani, Payal Skelly, Tara Soloway, Matthew G. Sougnez, Carrie Tam, Angela Tan, Donghui Thiessen, Nina Veluvolu, Umadevi Wang, Min Wilkerson, Matthew D. Wong, Tina Wu, Junyuan Xi, Liu Zhou, Jane Bedford, Jason Chen, Fengju Fu, Yao Gerstein, Mark Haussler, David Kasaian, Katayoon Lai, Phillip Ling, Shiyun Radenbaugh, Amie Van Den Berg, David Weinstein, John N. Zhu, Jingchun Albert, Monique Alexopoulou, Iakovina Andersen, Jeremiah J. Auman, J. Todd Bartlett, John Bastacky, Sheldon Bergsten, Julie Blute, Michael L. Boice, Lori Bollag, Roni J. Boyd, Jeff Castle, Erik Chen, Ying-Bei Cheville, John C. Curley, Erin Davies, Benjamin DeVolk, April Dhir, Rajiv Dike, Laura Eckman, John Engel, Jay Harr, Jodi Hrebinko, Ronald Huang, Mei Huelsenbeck-Dill, Lori Iacocca, Mary Jacobs, Bruce Lobis, Michael Maranchie, Jodi K. McMeekin, Scott Myers, Jerome Nelson, Joel Parfitt, Jeremy Parwani, Anil Petrelli, Nicholas Rabeno, Brenda Roy, Somak Salner, Andrew L. Slaton, Joel Stanton, Melissa Thompson, R. Houston Thorne, Leigh Tucker, Kelinda Weinberger, Paul M. Winemiller, Cynthia Zach, Leigh Anne Zuna, Rosemary CA Canc Genome Atlas Res Network TI Comprehensive Molecular Characterization of Papillary Renal-Cell Carcinoma SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Article ID KIDNEY CANCER; MET PROTOONCOGENE; GASTRIC ADENOCARCINOMA; GENETIC-BASIS; MUTATIONS; HEREDITARY; FUMARATE; TUMORS; NRF2; EXPRESSION AB BACKGROUND Papillary renal-cell carcinoma, which accounts for 15 to 20% of renal-cell carcinomas, is a heterogeneous disease that consists of various types of renal cancer, including tumors with indolent, multifocal presentation and solitary tumors with an aggressive, highly lethal phenotype. Little is known about the genetic basis of sporadic papillary renal-cell carcinoma, and no effective forms of therapy for advanced disease exist. METHODS We performed comprehensive molecular characterization of 161 primary papillary renal-cell carcinomas, using whole-exome sequencing, copy-number analysis, messenger RNA and microRNA sequencing, DNA-methylation analysis, and proteomic analysis. RESULTS Type 1 and type 2 papillary renal-cell carcinomas were shown to be different types of renal cancer characterized by specific genetic alterations, with type 2 further classified into three individual subgroups on the basis of molecular differences associated with patient survival. Type 1 tumors were associated with MET alterations, whereas type 2 tumors were characterized by CDKN2A silencing, SETD2 mutations, TFE3 fusions, and increased expression of the NRF2 antioxidant response element (ARE) pathway. A CpG island methylator phenotype (CIMP) was observed in a distinct subgroup of type 2 papillary renal-cell carcinomas that was characterized by poor survival and mutation of the gene encoding fumarate hydratase (FH). CONCLUSIONS Type 1 and type 2 papillary renal-cell carcinomas were shown to be clinically and biologically distinct. Alterations in the MET pathway were associated with type 1, and activation of the NRF2-ARE pathway was associated with type 2; CDKN2A loss and CIMP in type 2 conveyed a poor prognosis. Furthermore, type 2 papillary renal-cell carcinoma consisted of at least three subtypes based on molecular and phenotypic features. (Funded by the National Institutes of Health.) C1 [Linehan, W. Marston] NCI, Urol Oncol Branch, Bethesda, MD 20892 USA. RP Linehan, WM (reprint author), NCI, Urol Oncol Branch, Bldg 10 CRC Rm 1-5940, Bethesda, MD 20892 USA. EM wml@nih.gov RI Hirst, Martin/B-7684-2016; Marra, Marco/B-5987-2008; Holt, Robert/C-3303-2009; OI Bottaro, Donald/0000-0002-5057-5334; Maranchie, Jodi/0000-0002-8534-9468; Chen, Ying-Bei/0000-0001-5207-3648; Perou, Charles/0000-0001-9827-2247 FU National Institutes of Health [U54 HG003273, U54 HG003067, U54 HG003079, U24 CA143799, U24 CA143835, U24 CA143840, U24 CA143843, U24 CA143845, U24 CA143848, U24 CA143858, U24 CA143866, U24 CA143867, U24 CA143882, U24 CA143883, U24 CA144025, P30 CA016672] FX Supported by grants (U54 HG003273, U54 HG003067, U54 HG003079, U24 CA143799, U24 CA143835, U24 CA143840, U24 CA143843, U24 CA143845, U24 CA143848, U24 CA143858, U24 CA143866, U24 CA143867, U24 CA143882, U24 CA143883, U24 CA144025, and P30 CA016672) from the National Institutes of Health. NR 39 TC 78 Z9 78 U1 7 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 JAN 14 PY 2016 VL 374 IS 2 BP 135 EP 145 DI 10.1056/NEJMoa1505917 PG 11 WC Medicine, General & Internal SC General & Internal Medicine GA DA7PQ UT WOS:000367996700008 ER PT J AU Compton, WM Jones, CM Baldwin, GT AF Compton, Wilson M. Jones, Christopher M. Baldwin, Grant T. TI Relationship between Nonmedical Prescription-Opioid Use and Heroin Use SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Review ID NEW-YORK-CITY; INJECTION-DRUG USERS; UNITED-STATES; OVERDOSE DEATHS; RISK BEHAVIORS; YOUNG-ADULTS; ABUSE; EPIDEMIC; MISUSE; DEPENDENCE C1 [Compton, Wilson M.] NIDA, NIH, Silver Spring, MD USA. [Jones, Christopher M.] US FDA, Silver Spring, MD USA. [Baldwin, Grant T.] Ctr Dis Control & Prevent, Div Unintent Injury Prevent, Atlanta, GA USA. RP Compton, WM (reprint author), NIDA, NIH, 6001 Execut Blvd,MSC 9581, Bethesda, MD 20892 USA. EM wcompton@nida.nih.gov NR 65 TC 74 Z9 74 U1 10 U2 39 PU MASSACHUSETTS MEDICAL SOC PI WALTHAM PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA SN 0028-4793 EI 1533-4406 J9 NEW ENGL J MED JI N. Engl. J. Med. PD JAN 14 PY 2016 VL 374 IS 2 BP 154 EP 163 DI 10.1056/NEJMra1508490 PG 10 WC Medicine, General & Internal SC General & Internal Medicine GA DA7PQ UT WOS:000367996700010 PM 26760086 ER PT J AU Vance, TM Azabdaftari, G Pop, EA Lee, SG Su, LJ Fontham, ETH Bensen, JT Steck, SE Arab, L Mohler, JL Chen, MH Koo, SI Chun, OK AF Vance, Terrence M. Azabdaftari, Gissou Pop, Elena A. Lee, Sang Gil Su, L. Joseph Fontham, Elizabeth T. H. Bensen, Jeannette T. Steck, Susan E. Arab, Lenore Mohler, James L. Chen, Ming-Hui Koo, Sung I. Chun, Ock K. TI Intake of dietary antioxidants is inversely associated with biomarkers of oxidative stress among men with prostate cancer SO BRITISH JOURNAL OF NUTRITION LA English DT Article DE Prostate cancer; Diets; Antioxidants; Oxidative stress ID PLASMA ANTIOXIDANTS; LIPID-PEROXIDATION; RISK; THIOREDOXIN; POLYMORPHISMS; CAPACITY; DISEASE; XRCC1; CELLS AB Prostate cancer is the most common non-cutaneous cancer and the second leading cause of cancer-related mortality among men in the USA. Growing evidence suggests that oxidative stress is involved in the development and progression of prostate cancer. In this study, the association between antioxidants from diet and supplements and biomarkers of oxidative stress in blood (n 278), urine (n 298) and prostate tissue (n 55) were determined among men from the North Carolina-Louisiana Prostate Cancer Project. The association between antioxidant intake and oxidative stress biomarkers in blood and urine was determined using linear regression, adjusting for age, race, prostate cancer aggressiveness and smoking status. Greater antioxidant intake was found to be associated with lower urinary 8-isoprostane concentrations, with a 10 % increase in antioxidant intake corresponding to an unadjusted 1.1 % decrease in urinary 8-isoprostane levels (95 % CI -1.7, -0.3%; P value < 0.01) and an adjusted 0.6 % decrease (95 % CI -1.4, 0.2%; P value = 0.16). In benign prostate tissue, thioredoxin 1 was inversely associated with antioxidant intake (P = 0.02). No significant associations were found for other blood or urinary biomarkers or for malignant prostate tissue. These results indicate that antioxidant intake may be associated with less oxidative stress among men diagnosed with prostate cancer. C1 [Vance, Terrence M.; Lee, Sang Gil; Koo, Sung I.; Chun, Ock K.] Univ Connecticut, Dept Nutr Sci, Storrs, CT 06269 USA. [Azabdaftari, Gissou; Pop, Elena A.; Mohler, James L.] Roswell Pk Canc Inst, Buffalo, NY 14263 USA. [Su, L. Joseph] NCI, Epidemiol & Genom Res Program, Div Canc Control & Populat Sci, Bethesda, MD 20892 USA. [Fontham, Elizabeth T. H.] Louisiana State Univ, Hlth Sci Ctr, Sch Publ Hlth, New Orleans, LA 70112 USA. [Bensen, Jeannette T.; Mohler, James L.] Univ N Carolina, Sch Publ Hlth, Chapel Hill, NC 27599 USA. [Steck, Susan E.] Univ S Carolina, Canc Prevent & Control Program, Dept Epidemiol & Biostat, Columbia, SC 29208 USA. [Arab, Lenore] Univ Calif Los Angeles, David Geffen Sch Med, Los Angeles, CA 90095 USA. [Chen, Ming-Hui] Univ Connecticut, Dept Stat, Storrs, CT 06269 USA. RP Chun, OK (reprint author), Univ Connecticut, Dept Nutr Sci, Storrs, CT 06269 USA. EM ock.chun@uconn.edu FU National Institutes of Health Cancer Epidemiology small grant [1R03CA159421-01A1]; Department of Defense [DAMD 17-03-2-0052] FX This study was supported by the National Institutes of Health Cancer Epidemiology small grant no. 1R03CA159421-01A1 and Department of Defense contract DAMD 17-03-2-0052. NR 33 TC 2 Z9 2 U1 7 U2 15 PU CAMBRIDGE UNIV PRESS PI CAMBRIDGE PA EDINBURGH BLDG, SHAFTESBURY RD, CB2 8RU CAMBRIDGE, ENGLAND SN 0007-1145 EI 1475-2662 J9 BRIT J NUTR JI Br. J. Nutr. PD JAN 14 PY 2016 VL 115 IS 1 BP 68 EP 74 DI 10.1017/S0007114515004249 PG 7 WC Nutrition & Dietetics SC Nutrition & Dietetics GA CZ6TV UT WOS:000367234800009 PM 26521663 ER PT J AU Edelman, EJ Hansen, NB Cutter, CJ Danton, C Fiellin, LE O'Connor, PG Williams, EC Maisto, SA Bryant, KJ Fiellin, DA AF Edelman, E. Jennifer Hansen, Nathan B. Cutter, Christopher J. Danton, Cheryl Fiellin, Lynn E. O'Connor, Patrick G. Williams, Emily C. Maisto, Stephen A. Bryant, Kendall J. Fiellin, David A. TI Implementation of integrated stepped care for unhealthy alcohol use in HIV clinics SO ADDICTION SCIENCE & CLINICAL PRACTICE LA English DT Article DE HIV; Alcohol-related disorders; Qualitative methods; Diffusion of innovation ID HUMAN-IMMUNODEFICIENCY-VIRUS; SUBSTANCE-ABUSE TREATMENT; QUALITATIVE CONTENT-ANALYSIS; CENTERED MEDICAL HOME; BRIEF INTERVENTION; ANTIRETROVIRAL THERAPY; INFECTED PATIENTS; USE DISORDERS; EMERGENCY-DEPARTMENT; HEPATITIS-C AB Background: Effective counseling and pharmacotherapy for unhealthy alcohol use are rarely provided in HIV treatment settings to patients. Our goal was to describe factors influencing implementation of a stepped care model to address unhealthy alcohol use in HIV clinics from the perspectives of social workers, psychologists and addiction psychiatrists. Methods: We conducted two focus groups with Social Workers (n = 4), Psychologists (n = 2), and Addiction Psychiatrists (n = 4) involved in an ongoing randomized controlled trial evaluating the effectiveness of integrated stepped care for unhealthy alcohol use in HIV-infected patients at five Veterans Health Administration (VA) HIV clinics. Data collection and analyses were guided by the Consolidated Framework for Implementation Research (CFIR) domains, with a focus on the three domains which we considered to be most relevant: intervention characteristics (i.e. motivational interviewing, pharmacotherapy), the inner setting (i.e. HIV clinics), and characteristics of individuals (i.e. the providers). A multidisciplinary team used directed content analysis to identify major themes. Results: From the providers' perspective, the major implementation themes that emerged by CFIR domain included: (1) Intervention characteristics: providers valued tools and processes for facilitating patient motivation for treatment of unhealthy alcohol use given their perceived lack of motivation, but expressed a desire for greater flexibility; (2) Inner setting: treating unhealthy alcohol use in HIV clinics was perceived by providers to be consistent with VA priorities; and (3) Characteristics of individuals: there was high self-efficacy to conduct the intervention, an expressed need for more consistent utilization to maintain skills, and consideration of alternative models for delivering the components of the intervention. Conclusions: Use of the CFIR framework reveals that implementation of integrated stepped care for unhealthy alcohol use in HIV clinics is facilitated by tools to help providers enhance patient motivation or address unhealthy alcohol use among patients perceived to be unmotivated. Implementation may be facilitated by its consistency with organizational values and existing models of care and attention to optimizing provider self-efficacy and roles (i.e. approaches to treatment integration). C1 [Edelman, E. Jennifer; Cutter, Christopher J.; Danton, Cheryl; Fiellin, Lynn E.; O'Connor, Patrick G.; Fiellin, David A.] Yale Univ, Sch Med, ESH A, 367 Cedar St, New Haven, CT 06510 USA. [Edelman, E. Jennifer; Hansen, Nathan B.; Fiellin, Lynn E.; Fiellin, David A.] Yale Univ, Sch Publ Hlth, Ctr Interdisciplinary Res AIDS, 135 Coll St, New Haven, CT 06510 USA. [Hansen, Nathan B.] Univ Georgia, Coll Publ Hlth, 131 Wright Hall,Hlth Sci Campus, Athens, GA 30602 USA. [Williams, Emily C.] VA Puget Sound Hlth Care Syst, Ctr Innovat Veteran Ctr & Value Driven Care, 1100 Olive Way,Suite 1400, Seattle, WA 98101 USA. [Williams, Emily C.] Univ Washington, Dept Hlth Serv, Magnuson Hlth Sci Ctr, 1959 NE Pacific St,Room H-664, Seattle, WA 98195 USA. [Maisto, Stephen A.] Syracuse Univ, 430 Huntington Hall, Syracuse, NY 13244 USA. [Bryant, Kendall J.] NIAAA, HIV AIDS Program, 5635 Fishers Lane, Bethesda, MD 20892 USA. RP Edelman, EJ (reprint author), Yale Univ, Sch Med, ESH A, 367 Cedar St, New Haven, CT 06510 USA. EM ejennifer.edelman@yale.edu RI Hansen, Nathan/F-2074-2016 FU NIAAA NIH HHS [K05 AA016928, 1U01AA020795, 2K05 AA16928, U01 AA020795]; NIDA NIH HHS [K12 DA033312, K12DA033312-02]; NIMH NIH HHS [R25 MH080916, R25 MH080916-01A2] NR 78 TC 3 Z9 3 U1 6 U2 6 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1940-0640 J9 ADDICT SCI CLIN PRAC JI Addict. Sci. Clin. Pract. PD JAN 13 PY 2016 VL 11 AR 1 DI 10.1186/s13722-015-0048-z PG 14 WC Substance Abuse SC Substance Abuse GA DP0AC UT WOS:000378148900001 PM 26763048 ER PT J AU Park, S Buck, MD Desai, C Zhang, X Loginicheva, E Martinez, J Freeman, ML Saitoh, T Akira, S Guan, JL He, YW Blackman, MA Handley, SA Levine, B Green, DR Reese, TA Artyomov, MN Virgin, HW AF Park, Sunmin Buck, Michael D. Desai, Chandni Zhang, Xin Loginicheva, Ekaterina Martinez, Jennifer Freeman, Michael L. Saitoh, Tatsuya Akira, Shizuo Guan, Jun-Lin He, You-Wen Blackman, Marcia A. Handley, Scott A. Levine, Beth Green, Douglas R. Reese, Tiffany A. Artyomov, Maxim N. Virgin, Herbert W. TI Autophagy Genes Enhance Murine Gammaherpesvirus 68 Reactivation from Latency by Preventing Virus-Induced Systemic Inflammation SO CELL HOST & MICROBE LA English DT Article ID GAMMA-INTERFERON; KAPOSIS-SARCOMA; IN-VIVO; DEFICIENT MICE; LYMPHOPROLIFERATIVE DISEASE; IL-1-BETA PRODUCTION; HERPESVIRUS LATENCY; DNA-SEQUENCES; T-CELLS; B-CELLS AB Host genes that regulate systemic inflammation upon chronic viral infection are incompletely understood. Murine gammaherpesvirus 68 (MHV68) infection is characterized by latency in macrophages, and reactivation is inhibited by interferon-gamma (IFN-gamma). Using a lysozyme-M-cre (LysMcre) expression system, we show that deletion of autophagy-related (Atg) genes Fip200, beclin 1, Atg14, Atg16l1, Atg7, Atg3, and Atg5, in the myeloid compartment, inhibited MHV68 reactivation in macrophages. Atg5 deficiency did not alter reactivation from B cells, and effects on reactivation from macrophages were not explained by alterations in productive viral replication or the establishment of latency. Rather, chronic MHV68 infection triggered increased systemic inflammation, increased T cell production of IFN-gamma, and an IFN-gamma-induced transcriptional signature in macrophages from Atg gene-deficient mice. The Atg5-related reactivation defect was partially reversed by neutralization of IFN-gamma. Thus Atg genes in myeloid cells dampen virus-induced systemic inflammation, creating an environment that fosters efficient MHV68 reactivation from latency. C1 [Park, Sunmin; Buck, Michael D.; Desai, Chandni; Zhang, Xin; Loginicheva, Ekaterina; Handley, Scott A.; Artyomov, Maxim N.; Virgin, Herbert W.] Washington Univ, Dept Pathol & Immunol, St Louis, MO 63110 USA. [Martinez, Jennifer] NIEHS, Immun Inflammat & Dis Lab, NIH, Res Triangle Pk, NC 27703 USA. [Freeman, Michael L.] Case Western Reserve Univ, Div Infect Dis, Cleveland, OH 44106 USA. [Saitoh, Tatsuya] Univ Tokushima, Inst Enzyme Res, Div Mol Genet, 3-8-15 Kuramoto Cho, Tokushima 7708503, Japan. [Akira, Shizuo] Osaka Univ, Microbial Dis Res Inst, Dept Host Def, 3-1 Yamada Oka, Suita, Osaka 5650871, Japan. [Guan, Jun-Lin] Univ Cincinnati, Coll Med, Dept Canc Biol, Cincinnati, OH 45267 USA. [He, You-Wen] Duke Univ, Med Ctr, Dept Immunol, Durham, NC 27710 USA. [Blackman, Marcia A.] Trudeau Inst, Saranac Lake, NY 12983 USA. [Levine, Beth] Univ Texas SW Med Ctr Dallas, Dept Internal Med, Ctr Autophagy Res, Dallas, TX 75390 USA. [Levine, Beth] Univ Texas SW Med Ctr Dallas, Howard Hughes Med Inst, Dallas, TX 75390 USA. [Green, Douglas R.] St Jude Childrens Res Hosp, Dept Immunol, 332 N Lauderdale St, Memphis, TN 38105 USA. [Reese, Tiffany A.] Univ Texas SW Med Ctr Dallas, Dept Immunol & Microbiol, Dallas, TX 75390 USA. RP Virgin, HW (reprint author), Washington Univ, Dept Pathol & Immunol, St Louis, MO 63110 USA. EM virgin@wustl.edu RI Akira, Shizuo/C-3134-2009; OI Buck, Michael/0000-0002-9611-1199 FU NIH [P30AR048335, U19AI109725]; NSF Graduate Research Fellowship [DGE-1143954]; Damon Runyon Postdoctoral Fellowship FX We acknowledge Darren Kreamalmeyer for mouse colony management, Christine Yokoyama and Megan Baldridge for editing the manuscript, Kathy Sheehan for providing anti-IFN-gamma antibody, and Wayne Yokoyama for providing anti-NK1.1. Experimental support was provided by a core funded by NIH P30AR048335. H.W.V. and B.L. were supported by NIH award U19AI109725. M.D.B. was supported by NSF Graduate Research Fellowship DGE-1143954. T.A.R. was supported by a Damon Runyon Postdoctoral Fellowship. NR 83 TC 8 Z9 8 U1 3 U2 11 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 1931-3128 EI 1934-6069 J9 CELL HOST MICROBE JI Cell Host Microbe PD JAN 13 PY 2016 VL 19 IS 1 BP 91 EP 101 DI 10.1016/j.chom.2015.12.010 PG 11 WC Microbiology; Parasitology; Virology SC Microbiology; Parasitology; Virology GA DD3RI UT WOS:000369839900013 PM 26764599 ER PT J AU Lu, Q Yokoyama, CC Williams, JW Baldridge, MT Jin, XH DesRochers, B Bricker, T Wilen, CB Bagaitkar, J Loginicheva, E Sergushichev, A Kreamalmeyer, D Keller, BC Zhao, Y Kambal, A Green, DR Martinez, J Dinauer, MC Holtzman, MJ Crouch, EC Beatty, W Boon, ACM Zhang, H Randolph, GJ Artyomov, MN Virgin, HW AF Lu, Qun Yokoyama, Christine C. Williams, Jesse W. Baldridge, Megan T. Jin, Xiaohua DesRochers, Brittany Bricker, Traci Wilen, Craig B. Bagaitkar, Juhi Loginicheva, Ekaterina Sergushichev, Alexey Kreamalmeyer, Darren Keller, Brian C. Zhao, Yan Kambal, Amal Green, Douglas R. Martinez, Jennifer Dinauer, Mary C. Holtzman, Michael J. Crouch, Erika C. Beatty, Wandy Boon, Adrianus C. M. Zhang, Hong Randolph, Gwendalyn J. Artyomov, Maxim N. Virgin, Herbert W. TI Homeostatic Control of Innate Lung Inflammation by Vici Syndrome Gene Epg5 and Additional Autophagy Genes Promotes Influenza Pathogenesis SO CELL HOST & MICROBE LA English DT Article ID RESPIRATORY VIRAL-INFECTION; CELLS REQUIRE AUTOPHAGY; VIRUS-INFECTION; PHOSPHATIDYLINOSITOL 3-KINASE; IL-1-BETA PRODUCTION; IMMUNE-RESPONSE; T-LYMPHOCYTES; BECLIN 1; GM-CSF; MICE AB Mutations in the autophagy gene EPG5 are linked to the multisystem human disease Vici syndrome, which is characterized in part by pulmonary abnormalities, including recurrent infections. We found that Epg5-deficient mice exhibited elevated baseline innate immune cellular and cytokine-based lung inflammation and were resistant to lethal influenza virus infection. Lung transcriptomics, bone marrow transplantation experiments, and analysis of cellular cytokine expression indicated that Epg5 plays a role in lung physiology through its function in macrophages. Deletion of other autophagy genes including Atg14, Fip200, Atg5, and Atg7 in myeloid cells also led to elevated basal lung inflammation and influenza resistance. This suggests that Epg5 and other Atg genes function in macrophages to limit innate immune inflammation in the lung. Disruption of this normal homeostatic dampening of lung inflammation results in increased resistance to influenza, suggesting that normal homeostatic mechanisms that limit basal tissue inflammation support some infectious diseases. C1 [Lu, Qun; Yokoyama, Christine C.; Williams, Jesse W.; Baldridge, Megan T.; Wilen, Craig B.; Bagaitkar, Juhi; Loginicheva, Ekaterina; Sergushichev, Alexey; Kreamalmeyer, Darren; Keller, Brian C.; Kambal, Amal; Dinauer, Mary C.; Crouch, Erika C.; Randolph, Gwendalyn J.; Artyomov, Maxim N.; Virgin, Herbert W.] Washington Univ, Sch Med, Dept Pathol & Immunol, St Louis, MO 63110 USA. [Jin, Xiaohua; DesRochers, Brittany; Bricker, Traci; Keller, Brian C.; Holtzman, Michael J.; Boon, Adrianus C. M.] Washington Univ, Sch Med, Dept Internal Med Pulm & Crit Care Med, St Louis, MO 63110 USA. [Beatty, Wandy] Washington Univ, Sch Med, Dept Mol Microbiol, St Louis, MO 63110 USA. [Bagaitkar, Juhi; Dinauer, Mary C.] Washington Univ, Sch Med, Dept Pediat Hematol Oncol, St Louis, MO 63110 USA. [Sergushichev, Alexey] ITMO Univ, Comp Technol Dept, St Petersburg 197101, Russia. [Zhao, Yan; Zhang, Hong] Chinese Acad Sci, Inst Biophys, State Key Lab Biomacromol, Beijing 100101, Peoples R China. [Green, Douglas R.] St Jude Childrens Res Hosp, Dept Immunol, 332 N Lauderdale St, Memphis, TN 38105 USA. [Martinez, Jennifer] NIEHS, Immun Inflammat & Dis Lab, NIH, Res Triangle Pk, NC 27703 USA. RP Virgin, HW (reprint author), Washington Univ, Sch Med, Dept Pathol & Immunol, St Louis, MO 63110 USA. EM virgin@wustl.edu RI Sergushichev, Alexey/J-8756-2015; OI Sergushichev, Alexey/0000-0003-1159-7220; Wilen, Craig/0000-0003-2495-9403; Williams, Jesse/0000-0003-3815-0891; Baldridge, Megan/0000-0002-7030-6131 FU NIH [U19AI109725, U19AI070489, RO1AI111605, RO1HL121791, AI049653, T32AI007163, T32DK7296, T32CA009547, T32HL07317]; WM Keck Fellowship from Washington University; Washington University School of Medicine; Children's Discovery Institute of Washington University and St. Louis Children's Hospital; Howard Hughes Medical Institute; National Basic Research Program of China [2013CB910100] FX We thank Xinyu Wang and Stoyan Ivanov for technical assistance. This work was supported by NIH awards U19AI109725 (H.W.V.), U19AI070489 (M.J.H.), RO1AI111605 (M.J.H.), RO1HL121791 (M.J.H.), and AI049653 (G.J.R.) and training grants T32AI007163 (C.C.Y.), T32DK7296 (J.W.W.), T32CA009547 (M.T.B.), and T32HL07317 (B.C.K.). This work was also supported by the WM Keck Fellowship from Washington University (M.T.B.), Washington University School of Medicine (A.C.M.B.), the Children's Discovery Institute of Washington University and St. Louis Children's Hospital (M.C.D., J.B.), the Howard Hughes Medical Institute (H.Z.), and grant 2013CB910100 from the National Basic Research Program of China (H.Z.). NR 76 TC 15 Z9 15 U1 3 U2 10 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 1931-3128 EI 1934-6069 J9 CELL HOST MICROBE JI Cell Host Microbe PD JAN 13 PY 2016 VL 19 IS 1 BP 102 EP 113 DI 10.1016/j.chom.2015.12.011 PG 12 WC Microbiology; Parasitology; Virology SC Microbiology; Parasitology; Virology GA DD3RI UT WOS:000369839900014 PM 26764600 ER PT J AU Ferreira, VP Vale, VF Pangburn, MK Abdeladhim, M Mendes-Sousa, AF Coutinho-Abreu, IV Rasouli, M Brandt, EA Meneses, C Lima, KF Araujo, RN Pereira, MH Kotsyfakis, M Oliveira, F Kamhawi, S Ribeiro, JMC Gontijo, NF Collin, N Valenzuela, JG AF Ferreira, Viviana P. Vale, Vladimir Fazito Pangburn, Michael K. Abdeladhim, Maha Mendes-Sousa, Antonio Ferreira Coutinho-Abreu, Iliano V. Rasouli, Manoochehr Brandt, Elizabeth A. Meneses, Claudio Lima, Kolyvan Ferreira Araujo, Ricardo Nascimento Pereira, Marcos Horacio Kotsyfakis, Michalis Oliveira, Fabiano Kamhawi, Shaden Ribeiro, Jose M. C. Gontijo, Nelder F. Collin, Nicolas Valenzuela, Jesus G. TI SALO, a novel classical pathway complement inhibitor from saliva of the sand fly Lutzomyia longipalpis SO SCIENTIFIC REPORTS LA English DT Article ID LEISHMANIA-BRAZILIENSIS; ARTHROPOD SALIVA; 2 PARTS; PROTEIN; IMMUNITY; VECTOR; SYSTEM; HOST; ACTIVATION; GLANDS AB Blood-feeding insects inject potent salivary components including complement inhibitors into their host's skin to acquire a blood meal. Sand fly saliva was shown to inhibit the classical pathway of complement; however, the molecular identity of the inhibitor remains unknown. Here, we identified SALO as the classical pathway complement inhibitor. SALO, an 11 kDa protein, has no homology to proteins of any other organism apart from New World sand flies. rSALO anti-complement activity has the same chromatographic properties as the Lu. longipalpis salivary gland homogenate (SGH) counterparts and anti-rSALO antibodies blocked the classical pathway complement activity of rSALO and SGH. Both rSALO and SGH inhibited C4b deposition and cleavage of C4. rSALO, however, did not inhibit the protease activity of C1s nor the enzymatic activity of factor Xa, uPA, thrombin, kallikrein, trypsin and plasmin. Importantly, rSALO did not inhibit the alternative or the lectin pathway of complement. In conclusion our data shows that SALO is a specific classical pathway complement inhibitor present in the saliva of Lu. longipalpis. Importantly, due to its small size and specificity, SALO may offer a therapeutic alternative for complement classical pathway-mediated pathogenic effects in human diseases. C1 [Ferreira, Viviana P.] Univ Toledo, Dept Med Microbiol & Immunol, Coll Med & Life Sci, Belo Horizonte, MG, Brazil. [Vale, Vladimir Fazito; Mendes-Sousa, Antonio Ferreira; Lima, Kolyvan Ferreira; Araujo, Ricardo Nascimento; Pereira, Marcos Horacio; Gontijo, Nelder F.] Univ Fed Minas Gerais, Dept Parasitol, Lab Fisiol Insetos Hematofagos, Belo Horizonte, MG, Brazil. [Pangburn, Michael K.] Univ Texas Hlth Sci Ctr Tyler, Tyler, TX USA. [Abdeladhim, Maha; Mendes-Sousa, Antonio Ferreira; Coutinho-Abreu, Iliano V.; Rasouli, Manoochehr; Brandt, Elizabeth A.; Meneses, Claudio; Oliveira, Fabiano; Kamhawi, Shaden; Collin, Nicolas; Valenzuela, Jesus G.] NIAID, Vector Mol Biol Sect, LMVR, NIH, Rockville, MD USA. [Kotsyfakis, Michalis] Acad Sci Czech Republic, Ctr Biol, CZ-37005 Budweis, Czech Republic. [Ribeiro, Jose M. C.] NIAID, Vector Biol Sect, LMVR, NIH, Rockville, MD USA. [Collin, Nicolas] Univ Lausanne, Dept Biochem, Vaccine Formulat Lab, CH-1015 Lausanne, Switzerland. RP Gontijo, NF (reprint author), Univ Fed Minas Gerais, Dept Parasitol, Lab Fisiol Insetos Hematofagos, Belo Horizonte, MG, Brazil.; Collin, N; Valenzuela, JG (reprint author), NIAID, Vector Mol Biol Sect, LMVR, NIH, Rockville, MD USA.; Collin, N (reprint author), Univ Lausanne, Dept Biochem, Vaccine Formulat Lab, CH-1015 Lausanne, Switzerland. EM nelder@icb.ufmg.br; nicolas.collin@unil.ch; jvalenzuela@niaid.nih.gov RI Kotsyfakis, Michail/G-9525-2014; Pereira, Marcos/A-3774-2012; OI Kotsyfakis, Michail/0000-0002-7526-1876; Ferreira, Viviana/0000-0001-8923-5671; Ribeiro, Jose/0000-0002-9107-0818 FU Intramural Research Program of the NIH, National Institute of Allergy and Infectious Diseases; National Institutes of Health [DK-35081]; University of Toledo; FAPEMIG; CAPES; Grant Agency of the Czech Republic (GACR) [P502/12/2409]; CNPq-Brasil FX We would like to thank Mr. Carl W. Rhodes and Mr. Christopher A. Robles for helping us to rear the sand flies and dissect sand fly salivary glands needed for this paper. This research was supported in part by the Intramural Research Program of the NIH, National Institute of Allergy and Infectious Diseases (JGV, JMCR, FO, SK, MA, IVC, MR, AFMS, CM and EAB); MKP, supported by National Institutes of Health Grant DK-35081; VPF, supported by University of Toledo startup funds; NFG, VFV and RNA, supported by FAPEMIG and CAPES, the Brazilian Government for the qualification of human resources, MK, supported by the Grant Agency of the Czech Republic (GACR grant P502/12/2409); AFMS was partially supported by CNPq-Brasil. NR 43 TC 4 Z9 4 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 JAN 13 PY 2016 VL 6 AR 19300 DI 10.1038/srep19300 PG 13 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA DC2RJ UT WOS:000369063700001 PM 26758086 ER PT J AU de Celles, MD Magpantay, FMG King, AA Rohani, P AF de Celles, Matthieu Domenech Magpantay, Felicia M. G. King, Aaron A. Rohani, Pejman TI The pertussis enigma: reconciling epidemiology, immunology and evolution SO PROCEEDINGS OF THE ROYAL SOCIETY B-BIOLOGICAL SCIENCES LA English DT Article DE pertussis; pertussis epidemiology; pertussis vaccines; pertussis resurgence; vaccine-derived immunity; infection-derived immunity ID BORDETELLA-PARAPERTUSSIS INFECTION; VACCINE EFFICACY; WHOLE-CELL; CHANGING EPIDEMIOLOGY; BOOSTER VACCINATION; MASS VACCINATION; ADULT PERTUSSIS; UNITED-STATES; YOUNG INFANTS; HERD-IMMUNITY AB Pertussis, a highly contagious respiratory infection, remains a public health priority despite the availability of vaccines for 70 years. Still a leading cause of mortality in developing countries, pertussis has re-emerged in several developed countries with high vaccination coverage. Resurgence of pertussis in these countries has routinely been attributed to increased awareness of the disease, imperfect vaccinal protection or high infection rates in adults. In this review, we first present 1980-2012 incidence data from 63 countries and show that pertussis resurgence is not universal. We further argue that the large geographical variation in trends probably precludes a simple explanation, such as the transition from whole-cell to acellular pertussis vaccines. Reviewing available evidence, we then propose that prevailing views on pertussis epidemiology are inconsistent with both historical and contemporary data. Indeed, we summarize epidemiological evidence showing that natural infection and vaccination both appear to provide long-term protection against transmission and disease, so that previously infected or vaccinated adults contribute little to overall transmission at a population level. Finally, we identify several promising avenues that may lead to a consistent explanation of global pertussis epidemiology and to more effective control strategies. C1 [de Celles, Matthieu Domenech; Magpantay, Felicia M. G.; King, Aaron A.] Univ Michigan, Dept Ecol & Evolutionary Biol, Ann Arbor, MI 48109 USA. [King, Aaron A.] Univ Michigan, Dept Math, Ann Arbor, MI 48109 USA. [King, Aaron A.; Rohani, Pejman] NIH, Fogarty Int Ctr, Bethesda, MD 20892 USA. [Rohani, Pejman] Univ Georgia, Odum Sch Ecol, Athens, GA 30602 USA. [Rohani, Pejman] Univ Georgia, Coll Vet Med, Athens, GA 30602 USA. RP Rohani, P (reprint author), NIH, Fogarty Int Ctr, Bethesda, MD 20892 USA.; Rohani, P (reprint author), Univ Georgia, Odum Sch Ecol, Athens, GA 30602 USA.; Rohani, P (reprint author), Univ Georgia, Coll Vet Med, Athens, GA 30602 USA. EM rohani@uga.edu FU Research and Policy in Infectious Disease Dynamics programme of the Science and Technology Directorate, Department of Homeland Security, the Fogarty International Center, National Institutes of Health; National Institutes of Health [1R01AI101155]; MIDAS, National Institute of General Medical Sciences [U54-GM111274] FX P.R. and A.A.K. are supported by the Research and Policy in Infectious Disease Dynamics programme of the Science and Technology Directorate, Department of Homeland Security, the Fogarty International Center, National Institutes of Health, by a research grant from the National Institutes of Health (1R01AI101155) and by MIDAS, National Institute of General Medical Sciences U54-GM111274. The funding sources had no role in the study design, in the collection, analysis and interpretation of data, in the writing of the report, and in the decision to submit the paper for publication. NR 94 TC 1 Z9 1 U1 0 U2 11 PU ROYAL SOC PI LONDON PA 6-9 CARLTON HOUSE TERRACE, LONDON SW1Y 5AG, ENGLAND SN 0962-8452 EI 1471-2954 J9 P ROY SOC B-BIOL SCI JI Proc. R. Soc. B-Biol. Sci. PD JAN 13 PY 2016 VL 283 IS 1822 AR 20152309 DI 10.1098/rspb.2015.2309 PG 10 WC Biology; Ecology; Evolutionary Biology SC Life Sciences & Biomedicine - Other Topics; Environmental Sciences & Ecology; Evolutionary Biology GA DB3VN UT WOS:000368441200011 ER PT J AU Ruffo, E Malacarne, V Larsen, SE Das, R Patrussi, L Wulfing, C Biskup, C Kapnick, SM Verbist, K Tedrick, P Schwartzberg, PL Baldari, CT Rubio, I Nichols, KE Snow, AL Baldanzi, G Graziani, A AF Ruffo, Elisa Malacarne, Valeria Larsen, Sasha E. Das, Rupali Patrussi, Laura Wuelfing, Christoph Biskup, Christoph Kapnick, Senta M. Verbist, Katherine Tedrick, Paige Schwartzberg, Pamela L. Baldari, Cosima T. Rubio, Ignacio Nichols, Kim E. Snow, Andrew L. Baldanzi, Gianluca Graziani, Andrea TI Inhibition of diacylglycerol kinase a restores restimulation-induced cell death and reduces immunopathology in XLP-1 SO SCIENCE TRANSLATIONAL MEDICINE LA English DT Article ID LINKED LYMPHOPROLIFERATIVE DISEASE; T-CELLS; PKC-THETA; IMMUNOLOGICAL SYNAPSE; C-THETA; SAP; ACTIVATION; APOPTOSIS; RECEPTORS; RESPONSES AB X-linked lymphoproliferative disease (XLP-1) is an often-fatal primary immunodeficiency associated with the exuberant expansion of activated CD8(+) T cells after Epstein-Barr virus (EBV) infection. XLP-1 is caused by defects in signaling lymphocytic activation molecule (SLAM)-associated protein (SAP), an adaptor protein that modulates T cell receptor (TCR)-induced signaling. SAP-deficient T cells exhibit impaired TCR restimulation-induced cell death (RICD) and diminished TCR-induced inhibition of diacylglycerol kinase alpha (DGK alpha), leading to increased diacylglycerol metabolism and decreased signaling through Ras and PKC theta (protein kinase C theta). We show that down-regulation of DGKa activity in SAP-deficient T cells restores diacylglycerol signaling at the immune synapse and rescues RICD via induction of the proapoptotic proteins NUR77 and NOR1. Pharmacological inhibition of DGK alpha prevents the excessive CD8(+) T cell expansion and interferon-gamma production that occur in SAP-deficient mice after lymphocytic choriomeningitis virus infection without impairing lytic activity. Collectively, these data highlight DGK alpha as a viable therapeutic target to reverse the life-threatening EBV-associated immunopathology that occurs in XLP-1 patients. C1 [Ruffo, Elisa; Malacarne, Valeria; Baldanzi, Gianluca; Graziani, Andrea] Univ Piemonte Orientale, Dept Translat Med, I-28100 Novara, Italy. [Ruffo, Elisa; Malacarne, Valeria; Baldanzi, Gianluca; Graziani, Andrea] Univ Piemonte Orientale, Inst Res & Cure Autoimmune Dis, I-28100 Novara, Italy. [Larsen, Sasha E.; Snow, Andrew L.] Uniformed Serv Univ Hlth Sci, Dept Pharmacol & Mol Therapeut, Bethesda, MD 20814 USA. [Das, Rupali] Michigan State Univ, Dept Physiol, E Lansing, MI 48824 USA. [Patrussi, Laura; Baldari, Cosima T.] Univ Siena, Dept Life Sci, I-53100 Siena, Italy. [Wuelfing, Christoph] Univ Bristol, Sch Cellular & Mol Med, Bristol BS8 1TH, Avon, England. [Biskup, Christoph] Jena Univ Hosp, Biomol Photon Grp, D-07740 Jena, Germany. [Kapnick, Senta M.; Schwartzberg, Pamela L.] NHGRI, Genet Dis Res Branch, NIH, Bethesda, MD 20892 USA. [Verbist, Katherine; Tedrick, Paige; Nichols, Kim E.] St Jude Childrens Res Hosp, Dept Oncol, 332 N Lauderdale, Memphis, TN 38105 USA. [Rubio, Ignacio] Jena Univ Hosp, Ctr Mol Biomed, Ctr Sepsis Control & Care, Integrated Res & Treatment Ctr, D-07745 Jena, Germany. [Rubio, Ignacio] Jena Univ Hosp, Ctr Mol Biomed, Inst Mol Cell Biol, D-07745 Jena, Germany. [Graziani, Andrea] Univ Vita Salute San Raffaele, Sch Med, I-20132 Milan, Italy. RP Graziani, A (reprint author), Univ Piemonte Orientale, Dept Translat Med, I-28100 Novara, Italy.; Graziani, A (reprint author), Univ Piemonte Orientale, Inst Res & Cure Autoimmune Dis, I-28100 Novara, Italy.; Graziani, A (reprint author), Univ Vita Salute San Raffaele, Sch Med, I-20132 Milan, Italy. EM graziani.andrea@hsr.it OI Snow, Andrew/0000-0002-8728-6691 FU XLP Research Trust; Sean Fischel Fund for HLH (hemophagocytic lymphohistiocytosis) research; NIH [1R01GM105821]; AIRC (Associazione Italiana per la Ricerca sul Cancro) [IG13524, IG5392]; University of Piemonte Orientale (Young Investigators); Compagnia di San Paolo; NIH K22 [1 K22 CA188149-01]; Fondazione Telethon FX K.N. was supported by the XLP Research Trust and the Sean Fischel Fund for HLH (hemophagocytic lymphohistiocytosis) research. A.L.S. and S.E.L. were supported by grants from the NIH (1R01GM105821), XLP Research Trust, and USUHS. A.G., E.R., and V.M. were supported by grants from Telethon (GGP10034 and GGP13254) and AIRC (Associazione Italiana per la Ricerca sul Cancro) (IG13524 and IG5392). G.B. is supported by the University of Piemonte Orientale (Young Investigators). V.M. was supported by a grant from the Compagnia di San Paolo. R.D. was supported by an NIH K22 grant (1 K22 CA188149-01). NR 41 TC 1 Z9 1 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 JAN 13 PY 2016 VL 8 IS 321 DI 10.1126/scitranslmed.aad1565 PG 14 WC Cell Biology; Medicine, Research & Experimental SC Cell Biology; Research & Experimental Medicine GA DB4VD UT WOS:000368510800005 ER PT J AU Clay, JR AF Clay, John R. TI A Novel Method for the Description of Voltage-Gated Ionic Currents Based on Action Potential Clamp Results-Application to Hippocampal Mossy Fiber Boutons SO FRONTIERS IN CELLULAR NEUROSCIENCE LA English DT Article DE rat hippocampus; action potential clamp; mathematical models; Goldman-Hodgkin-Katz; ion channels ID SQUID GIANT-AXON; SUPRACHIASMATIC NUCLEUS NEURONS; SODIUM-CHANNELS; POTASSIUM CHANNELS; CONDUCTANCE; SUBUNITS; BILAYERS; HODGKIN; BLOCK; NA+ AB Action potential clamp (AP-clamp) recordings of the delayed rectifier K+ current I-K and the fast activated Na+ current I-Na in rat hippocampal mossy fiber boutons (MFBs) are analyzed using a computational technique recently reported. The method is implemented using a digitized AP from an MFB and computationally applying that data set to published models of I-K and I-Na. These numerical results are compared with experimental AP-clamp recordings. The I-Na result is consistent with experiment; the I-K result is not. The difficulty with the I-K model concerns the fully activated current-voltage relation, which is described here by the Goldman-Hodgkin-Katz dependence on the driving force (V-E-K) rather than (V-E-K) itself, the standard model for this aspect of ion permeation. That revision leads to the second-a much steeper voltage dependent activation curve for I-K than the one obtained from normalization of a family of I-K records by (V-E-K). The revised model provides an improved description of the AP-clamp measurement of I-K in MFBs compared with the standard approach. The method described here is general. It can be used to test models of ionic currents in any excitable cell. In this way it provides a novel approach to the relationship between ionic current and membrane excitability in neurons. C1 [Clay, John R.] NINDS, Dept Physiol, NIH, Rockville, MD 20852 USA. RP Clay, JR (reprint author), NINDS, Dept Physiol, NIH, Rockville, MD 20852 USA. EM jrclay@ninds.nih.gov FU National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, Maryland USA FX This research was supported by the Intramural Research Program of the National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, Maryland USA. The author gratefully acknowledges Dr. Henrik Alle for providing a table of digitized results from Alle et al. (2009). NR 25 TC 0 Z9 0 U1 1 U2 7 PU FRONTIERS MEDIA SA PI LAUSANNE PA PO BOX 110, EPFL INNOVATION PARK, BUILDING I, LAUSANNE, 1015, SWITZERLAND SN 1662-5102 J9 FRONT CELL NEUROSCI JI Front. Cell. Neurosci. PD JAN 13 PY 2016 VL 9 DI 10.3389/fncel.2015.00514 PG 6 WC Neurosciences SC Neurosciences & Neurology GA DA8ET UT WOS:000368038600001 ER PT J AU Sukumar, M Liu, J Mehta, GU Patel, SJ Roychoudhuri, R Crompton, JG Klebanoff, CA Ji, Y Li, P Yu, ZY Whitehill, GD Clever, D Eil, RL Palmer, DC Mitra, S Rao, M Keyvanfar, K Schrump, DS Wang, E Marincola, FM Gattinoni, L Leonard, WJ Muranski, P Finkel, T Restifo, NP AF Sukumar, Madhusudhanan Liu, Jie Mehta, Gautam U. Patel, Shashank J. Roychoudhuri, Rahul Crompton, Joseph G. Klebanoff, Christopher A. Ji, Yun Li, Peng Yu, Zhiya Whitehill, Greg D. Clever, David Eil, Robert L. Palmer, Douglas C. Mitra, Suman Rao, Mahadev Keyvanfar, Keyvan Schrump, David S. Wang, Ena Marincola, Francesco M. Gattinoni, Luca Leonard, Warren J. Muranski, Pawel Finkel, Toren Restifo, Nicholas P. TI Mitochondrial Membrane Potential Identifies Cells with Enhanced Stemness for Cellular Therapy SO CELL METABOLISM LA English DT Article ID CD8(+) T-CELLS; METABOLIC-REGULATION; EFFECTOR FUNCTION; HYPOXIC NICHE; MEMORY; DIFFERENTIATION; ACTIVATION; REGULATOR; ANTIGEN; MTOR AB Long-term survival and antitumor immunity of adoptively transferred CD8(+) T cells is dependent on their metabolic fitness, but approaches to isolate therapeutic T cells based on metabolic features are not well established. Here we utilized a lipophilic cationic dye tetramethylrhodamine methyl ester (TMRM) to identify and isolate metabolically robust T cells based on their mitochondrial membrane potential (Delta psi m). Comprehensive metabolomic and gene expression profiling demonstrated global features of improved metabolic fitness in low-Delta psi m-sorted CD8(+) T cells. Transfer of these low-Delta psi m T cells was associated with superior long-term in vivo persistence and an enhanced capacity to eradicate established tumors compared with high-Delta psi m cells. Use ofDJm-based sorting to enrich for cells with superior metabolic features was observed in CD8(+), CD4(+) T cell subsets, and long-term hematopoietic stem cells. This metabolism-based approach to cell selection may be broadly applicable to therapies involving the transfer of HSC or lymphocytes for the treatment of viral-associated illnesses and cancer. C1 [Sukumar, Madhusudhanan; Mehta, Gautam U.; Patel, Shashank J.; Roychoudhuri, Rahul; Crompton, Joseph G.; Klebanoff, Christopher A.; Yu, Zhiya; Clever, David; Eil, Robert L.; Palmer, Douglas C.; Restifo, Nicholas P.] NCI, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. [Liu, Jie; Finkel, Toren] NHLBI, Ctr Mol Med, NIH, Bldg 10, Bethesda, MD 20892 USA. [Patel, Shashank J.] Georgetown Univ, Sch Med, Grad Partnership Program, NIH, Washington, DC 20007 USA. [Klebanoff, Christopher A.] NCI, Clin Investigator Dev Program, NIH, Bethesda, MD 20892 USA. [Ji, Yun; Gattinoni, Luca] NCI, Expt Transplantat & Immunol Branch, NIH, Bethesda, MD 20892 USA. [Li, Peng; Leonard, Warren J.] NHLBI, Lab Mol Immunol, NIH, Bldg 10, Bethesda, MD 20892 USA. [Li, Peng; Leonard, Warren J.] NHLBI, Ctr Immunol, NIH, Bldg 10, Bethesda, MD 20892 USA. [Whitehill, Greg D.; Keyvanfar, Keyvan; Muranski, Pawel] NHLBI, Hematol Branch, NIH, Bethesda, MD 20892 USA. [Clever, David] Ohio State Univ, Coll Med, Med Scientist Training Program, Columbus, OH 43210 USA. [Rao, Mahadev; Schrump, David S.] NCI, Thorac & GI Oncol Branch, NIH, Bethesda, MD 20892 USA. [Wang, Ena; Marincola, Francesco M.] Sidra Med & Res Ctr, Doha, Qatar. RP Sukumar, M; Restifo, NP (reprint author), NCI, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. EM sukumarm2@mail.nih.gov; restifo@nih.gov RI Gattinoni, Luca/A-2281-2008; Ji, Yun/B-7245-2009; Roychoudhuri, Rahul/A-7442-2010; OI Gattinoni, Luca/0000-0003-2239-3282; Ji, Yun/0000-0001-6340-7009; Roychoudhuri, Rahul/0000-0002-5392-1853; Mehta, Gautam/0000-0002-8009-6430 FU Intramural NIH HHS [Z99 CA999999]; Wellcome Trust [105663] NR 47 TC 15 Z9 15 U1 1 U2 8 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 JAN 12 PY 2016 VL 23 IS 1 BP 63 EP 76 DI 10.1016/j.cmet.2015.11.002 PG 14 WC Cell Biology; Endocrinology & Metabolism SC Cell Biology; Endocrinology & Metabolism GA DI6MO UT WOS:000373613400010 PM 26674251 ER PT J AU Cheng, AW Yang, Y Zhou, Y Maharana, C Lu, DY Peng, W Liu, Y Wan, RQ Marosi, K Misiak, M Bohr, VA Mattson, MP AF Cheng, Aiwu Yang, Ying Zhou, Ye Maharana, Chinmoyee Lu, Daoyuan Peng, Wei Liu, Yong Wan, Ruiqian Marosi, Krisztina Misiak, Magdalena Bohr, Vilhelm A. Mattson, Mark P. TI Mitochondrial SIRT3 Mediates Adaptive Responses of Neurons to Exercise and Metabolic and Excitatory Challenges SO CELL METABOLISM LA English DT Article ID NEURODEGENERATIVE DISORDERS; CALORIE RESTRICTION; LYSINE ACETYLATION; OXIDATIVE STRESS; SKELETAL-MUSCLE; INJURY; PGC-1-ALPHA; DEACETYLASE; EXPRESSION; PREVENTION AB The impact of mitochondrial protein acetylation status on neuronal function and vulnerability to neurological disorders is unknown. Here we show that the mitochondrial protein deacetylase SIRT3 mediates adaptive responses of neurons to bioenergetic, oxidative, and excitatory stress. Cortical neurons lacking SIRT3 exhibit heightened sensitivity to glutamate-induced calcium overload and excitotoxicity and oxidative and mitochondrial stress; AAV-mediated Sirt3 gene delivery restores neuronal stress resistance. In models relevant to Huntington's disease and epilepsy, Sirt3(-/-) mice exhibit increased vulnerability of striatal and hippocampal neurons, respectively. SIRT3 deficiency results in hyperacetylation of several mitochondrial proteins, including superoxide dismutase 2 and cyclophilin D. Running wheel exercise increases the expression of Sirt3 in hippocampal neurons, which is mediated by excitatory glutamatergic neurotransmission and is essential for mitochondrial protein acetylation homeostasis and the neuroprotective effects of running. Our findings suggest that SIRT3 plays pivotal roles in adaptive responses of neurons to physiological challenges and resistance to degeneration. C1 [Cheng, Aiwu; Yang, Ying; Zhou, Ye; Maharana, Chinmoyee; Lu, Daoyuan; Liu, Yong; Wan, Ruiqian; Marosi, Krisztina; Misiak, Magdalena; Mattson, Mark P.] Natl Inst Aging Intramural Res Program, Lab Neurosci, Baltimore, MD 21224 USA. [Yang, Ying] Wuhan Univ, Dept Neurol, Wuhan 430071, Hubei, Peoples R China. [Peng, Wei] Natl Inst Aging Intramural Res Program, Lab Genet, Baltimore, MD 21224 USA. [Marosi, Krisztina; Misiak, Magdalena] Natl Inst Aging Intramural Res Program, Lab Mol Gerontol, Baltimore, MD 21224 USA. [Mattson, Mark P.] Johns Hopkins Univ, Sch Med, Dept Neurosci, Baltimore, MD 21205 USA. RP Cheng, AW; Mattson, MP (reprint author), Natl Inst Aging Intramural Res Program, Lab Neurosci, Baltimore, MD 21224 USA.; Mattson, MP (reprint author), Johns Hopkins Univ, Sch Med, Dept Neurosci, Baltimore, MD 21205 USA. EM chengai@mail.nih.gov; mark.mattson@nih.gov OI Liu, Yong/0000-0003-1278-7114 FU Intramural Research Program of the National Institute on Aging; Glenn Foundation for Biomedical Research FX We thank Dr. David Gius (NCI) for providing breeding pairs of Sirt3-/- mice. This work was supported by the Intramural Research Program of the National Institute on Aging and the Glenn Foundation for Biomedical Research. NR 34 TC 14 Z9 15 U1 5 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 JAN 12 PY 2016 VL 23 IS 1 BP 128 EP 142 DI 10.1016/j.cmet.2015.10.013 PG 15 WC Cell Biology; Endocrinology & Metabolism SC Cell Biology; Endocrinology & Metabolism GA DI6MO UT WOS:000373613400015 PM 26698917 ER PT J AU Bao, W Tobias, DK Hu, FB Chavarro, JE Zhang, CL AF Bao, Wei Tobias, Deirdre K. Hu, Frank B. Chavarro, Jorge E. Zhang, Cuilin TI Pre-pregnancy potato consumption and risk of gestational diabetes mellitus: prospective cohort study SO BMJ-BRITISH MEDICAL JOURNAL LA English DT Article ID FRIED-FOOD-CONSUMPTION; CORONARY-HEART-DISEASE; DIETARY PATTERNS; GLYCEMIC INDEX; LIFE-STYLE; WOMEN; QUESTIONNAIRE; GLUCOSE; HEALTH; REPRODUCIBILITY AB STUDY QUESTION What is the association between potato consumption before pregnancy and the risk of gestational diabetes mellitus (GDM)? METHODS This prospective cohort study included 15 632 women from the Nurses' Health Study II (1991-2001). They had no previous GDM or chronic diseases before pregnancy. Consumption of potatoes and other foods was assessed every four years. Incident first time GDM was ascertained from self reports of a physician diagnosis of GDM, which was previously validated by medical records. STUDY ANSWER AND LIMITATIONS Over the 10 year follow-up there were 854 incident cases of GDM among 21 693 singleton pregnancies. After adjustment for age, parity, and dietary and non-dietary factors, women who consumed more potatoes before pregnancy had higher rates of developing GDM. Substitution of two servings a week of total potatoes with other vegetables, legumes, and whole grain foods was significantly associated with a 9-12% lower risk of GDM. Consumption and diabetes were self reported, and severity of diabetes was unknown. More than 90% of women were white. A causal association cannot be assumed. C1 [Bao, Wei; Zhang, Cuilin] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Epidemiol Branch, Div Intramural Populat Hlth Res, NIH, Rockville, MD 20852 USA. [Tobias, Deirdre K.] Brigham & Womens Hosp, Div Prevent Med, Boston, MA 02115 USA. [Tobias, Deirdre K.; Hu, Frank B.; Chavarro, Jorge E.] Harvard Univ, Sch Med, Boston, MA 02115 USA. [Tobias, Deirdre K.; Hu, Frank B.; Chavarro, Jorge E.] Harvard Univ, TH Chan Sch Publ Hlth, Dept Nutr, Boston, MA 02115 USA. [Hu, Frank B.; Chavarro, Jorge E.] Harvard Univ, TH Chan Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. [Hu, Frank B.; Chavarro, Jorge E.] Brigham & Womens Hosp, Dept Med, Channing Div Network Med, Boston, MA 02115 USA. RP Zhang, CL (reprint author), Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Epidemiol Branch, Div Intramural Populat Hlth Res, NIH, Rockville, MD 20852 USA. EM zhangcu@mail.nih.gov OI Bao, Wei/0000-0002-7301-5786 FU Intramural Research Program of Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health [HHSN275201000020C]; National Institutes of Health [DK58845, CA50385, P30 DK46200, UM1 CA176726]; American Diabetes Association [7-12-MN-34] FX This study was supported by the Intramural Research Program of the Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health (contract No HHSN275201000020C). The Nurses' Health Study II was funded by research grants DK58845, CA50385, P30 DK46200, and UM1 CA176726 from the National Institutes of Health. DKT and FBH were supported by a mentored fellowship from the American Diabetes Association (No 7-12-MN-34). NR 51 TC 12 Z9 12 U1 18 U2 27 PU BMJ PUBLISHING GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 1756-1833 J9 BMJ-BRIT MED J JI BMJ-British Medical Journal PD JAN 12 PY 2016 VL 352 AR h6898 DI 10.1136/bmj.h6898 PG 8 WC Medicine, General & Internal SC General & Internal Medicine GA DB2YB UT WOS:000368375500001 PM 26759275 ER PT J AU Volkow, ND AF Volkow, Nora D. TI Opioids in pregnancy SO BMJ-BRITISH MEDICAL JOURNAL LA English DT Editorial Material ID NEONATAL ABSTINENCE SYNDROME; ANALGESICS; EXPOSURE; OUTCOMES; SYSTEM; RISK C1 [Volkow, Nora D.] NIDA, NIH, Bethesda, MD 20892 USA. RP Volkow, ND (reprint author), NIDA, NIH, Bethesda, MD 20892 USA. EM nvolkow@nida.nih.gov NR 14 TC 1 Z9 1 U1 2 U2 6 PU BMJ PUBLISHING GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 1756-1833 J9 BMJ-BRIT MED J JI BMJ-British Medical Journal PD JAN 12 PY 2016 VL 352 AR i19 DI 10.1136/bmj.i19 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA DB2YB UT WOS:000368375500004 PM 26759359 ER PT J AU Gidding, SS Rana, JS Prendergast, C McGill, H Carr, JJ Liu, K Colangelo, LA Loria, CM Lima, J Terry, JG Reis, JP McMahan, CA AF Gidding, Samuel S. Rana, Jamal S. Prendergast, Christopher McGill, Henry Carr, J. Jeffery Liu, Kiang Colangelo, Laura A. Loria, Catherine M. Lima, Joao Terry, James G. Reis, Jared P. McMahan, C. Alex TI Pathobiological Determinants of Atherosclerosis in Youth (PDAY) Risk Score in Young Adults Predicts Coronary Artery and Abdominal Aorta Calcium in Middle Age The CARDIA Study SO CIRCULATION LA English DT Article DE atherosclerosis; coronary artery calcium; prevention & control; risk ID INTIMA-MEDIA THICKNESS; CARDIOVASCULAR RISK; SUBCLINICAL ATHEROSCLEROSIS; HEART-DISEASE; CALCIFICATION; CHILDHOOD; ASSOCIATION; FINNS; CT; REPRODUCIBILITY AB Background We explored whether, the Pathobiological Determinants of Atherosclerosis in Youth (PDAY) coronary and abdominal risk scores measured at 18 to 30 years of age and changes in these scores would more strongly predict coronary artery calcium (CAC) and abdominal aortic calcium (AAC) assessed 25 years later, than scores measured 25 years later. Methods and Results In the Coronary Artery Risk Development in Young Adults (CARDIA) study, 3008 participants had measurements of risk score components at 5-year intervals beginning at 18 to 30 years of age. CAC and AAC were assessed at 43 to 55 years of age. Odds ratios (ORs) for the presence and extent of CAC/AAC per/point higher score and c-statistics for predicting CAC/AAC were calculated. The prevalence of CAC was 28% and AAC was 53%. For each 1 point higher PDAY score, the odds of CAC were higher using baseline scores than year 25 scores (OR, 1.29; 95% confidence interval [CI], 1.25-1.33 versus OR, 1.12; 95% CI, 1.11-1.14). For AAC, ORs at years 0 and 25 were similar (OR, 1.29; 95% CI, 1.24-1.34 versus OR, 1.22; 95% CI, 1.19-1.26). C-statistic for CAC prediction was higher at year 0 than year 25 (0.731 versus 0.705) but similar at years 0 and 25 for AAC (0.665 versus 0.670). ORs for CAC were highest at baseline, and, for AAC, ORs were highest at year 10. Including change in PDAY scores with baseline scores improved prediction. Conclusions Atherosclerosis risk and change in risk assessed in young adulthood years before subclinical atherosclerosis imaging provide strong prediction of future subclinical atherosclerosis. CAC and AAC reflect chronic risk exposure in addition to risk measured at the time of study. C1 [Gidding, Samuel S.] Alfred I DuPont Hosp Children, Nemours Cardiac Ctr, Wilmington, DE USA. [Rana, Jamal S.] Kaiser Permanente No Calif, Div Cardiol, Oakland, CA USA. [Rana, Jamal S.] Kaiser Permanente No Calif, Div Res, Oakland, CA USA. [Rana, Jamal S.] Univ Calif San Francisco, Dept Med, San Francisco, CA 94143 USA. [Prendergast, Christopher] Vanderbilt Univ, Div Pediat Cardiol, Nashville, TN 37235 USA. [McGill, Henry; McMahan, C. Alex] Univ Texas Hlth Sci Ctr San Antonio, Dept Pathol, San Antonio, TX 78229 USA. [Carr, J. Jeffery; Terry, James G.] Vanderbilt Univ, Dept Radiol, Nashville, TN 37235 USA. [Carr, J. Jeffery; Terry, James G.] Vanderbilt Univ, Vanderbilt Translat & Clin Cardiovasc Res Ctr VTR, Nashville, TN 37235 USA. [Liu, Kiang; Colangelo, Laura A.] Northwestern Univ, Feinberg Sch Med, Dept Prevent Med, Chicago, IL 60611 USA. [Loria, Catherine M.; Reis, Jared P.] NHLBI, Div Cardiovasc Sci, Bethesda, MD 20892 USA. [Lima, Joao] Johns Hopkins Univ Hosp, Dept Internal Med, Baltimore, MD 21205 USA. RP Gidding, SS (reprint author), Nemours Cardiac Ctr, 1600 Rockland Rd, Wilmington, DE 19803 USA. EM sgidding@nemours.org FU National Heart, Lung, and Blood Institute (NHLBI) [HHSN268201300025C, HHSN268201300026C, HHSN268201300027C, HHSN268201300028C, HHSN268201300029C, HHSN268200900041C]; Intramural Research Program of the National Institute on Aging (NIA); NIA [AG0005]; NHLBI [AG0005] FX The Coronary Artery Risk Development in Young Adults Study (CARDIA) is supported by contracts HHSN268201300025C, HHSN268201300026C, HHSN268201300027C, HHSN268201300028C, HHSN268201300029C, and HHSN268200900041C from the National Heart, Lung, and Blood Institute (NHLBI), the Intramural Research Program of the National Institute on Aging (NIA), and an intra-agency agreement between NIA and NHLBI (AG0005). NR 32 TC 2 Z9 2 U1 1 U2 4 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 0009-7322 EI 1524-4539 J9 CIRCULATION JI Circulation PD JAN 12 PY 2016 VL 133 IS 2 BP 139 EP 146 DI 10.1161/CIRCULATIONAHA.115.018042 PG 8 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA DA6NV UT WOS:000367922700006 PM 27028434 ER PT J AU Tangri, N Grams, ME Levey, AS Coresh, J Appel, LJ Astor, BC Chodick, G Collins, AJ Djurdjev, O Elley, R Evans, M Garg, AX Hallan, SI Nicer, LA Ito, S Jee, SH Kovesdy, CP Kronenberg, F Heerspink, HJL Marks, A Nadkarni, GN Navaneethan, SD Nelson, RG Titze, S Sarnak, MJ Stengel, B Woodward, M Iseki, K AF Tangri, Navdeep Grams, Morgan E. Levey, Andrew S. Coresh, Josef Appel, Lawrence J. Astor, Brad C. Chodick, Gabriel Collins, Allan J. Djurdjev, Ognjenka Elley, Raina Evans, Marie Garg, Amit X. Hallan, Stein I. Nicer, Lesley A. Ito, Sadayoshi Jee, Sun Ha Kovesdy, Csaba P. Kronenberg, Florian Heerspink, Hiddo J. Lambers Marks, Angharad Nadkarni, Girish N. Navaneethan, Sankar D. Nelson, Robert G. Titze, Stephanie Sarnak, Mark J. Stengel, Benedicte Woodward, Mark Iseki, Kunitoshi CA CKD Prognosis Consortium TI Multinational Assessment of Accuracy of Equations for Predicting Risk of Kidney Failure A Meta-analysis SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Article ID GLOMERULAR-FILTRATION-RATE; STAGE RENAL-DISEASE; COLLABORATIVE METAANALYSIS; POPULATION COHORTS; HIGHER ALBUMINURIA; ESTIMATED GFR; DIABETIC-NEPHROPATHY; ALL-CAUSE; MORTALITY; ASSOCIATION AB IMPORTANCE Identifying patients at risk of chronic kidney disease (CKD) progression may facilitate more optimal nephrology care. Kidney failure risk equations were previously developed and validated in 2 Canadian cohorts. Validation in other regions and in CKD populations not under the care of a nephrologist is needed. OBJECTIVE To evaluate the accuracy of the risk equations across different geographic regions and patient populations through individual participant data meta-analysis. DATA SOURCES Thirty-one cohorts, including 721 357 participants with CKD stages 3 to 5 in more than 30 countries spanning 4 continents, were studied. These cohorts collected data from 1982 through 2014. STUDY SELECTION Cohorts participating in the CKD Prognosis Consortium with data on end-stage renal disease. DATA EXTRACTION AND SYNTHESIS Data were obtained and statistical analyses were performed between July 2012 and June 2015. Using the risk factors from the original risk equations, cohort-specific hazard ratios were estimated and combined in meta-analysis to form new pooled kidney failure risk equations. Original and pooled kidney failure risk equation performance was compared, and the need for regional calibration factors was assessed. MAIN OUTCOMES AND MEASURES Kidney failure (treatment by dialysis or kidney transplant). RESULTS During a median follow-up of 4 years, 23 829 cases of kidney failure were observed. The original risk equations achieved excellent discrimination (ability to differentiate those who developed kidney failure from those who did not) across all cohorts (overall C statistic, 0.90; 95% Cl, 0.89-0.92 at 2 years; C statistic, 0.88; 95% Cl, 0.86-0.90 at 5 years); discrimination in subgroups by age, race, and diabetes status was similar. There was no improvement with the pooled equations. Calibration (the difference between observed and predicted risk) was adequate in North American cohorts, but the original risk equations overestimated risk in some non-North American cohorts. Addition of a calibration factor that lowered the baseline risk by 32.9% at 2 years and 16.5% at 5 years improved the calibration in 12 of 15 and 10 of 13 non-North American cohorts at 2 and 5 years, respectively (P = .04 and P = .02). CONCLUSIONS AND RELEVANCE Kidney failure risk equations developed in a Canadian population showed high discrimination and adequate calibration when validated in 31 multinational cohorts. However, in some regions the addition of a calibration factor may be necessary. C1 [Tangri, Navdeep] Univ Manitoba, Dept Med, Oaks Gen Hosp 7, Winnipeg, MB, Canada. [Tangri, Navdeep] Univ Manitoba, Dept Community Hlth Sci, Oaks Gen Hosp 7, Winnipeg, MB R3T 2N2, Canada. [Grams, Morgan E.; Appel, Lawrence J.] Johns Hopkins Med Inst, Baltimore, MD 21205 USA. [Levey, Andrew S.; Sarnak, Mark J.] Tufts Med Ctr, Div Nephrol, Boston, MA USA. [Coresh, Josef; Appel, Lawrence J.; Woodward, Mark] Johns Hopkins Bloomberg Sch Publ Hlth, Baltimore, MD USA. [Astor, Brad C.] Univ Wisconsin, Dept Med, Sch Med & Publ Hlth, Madison, WI 53706 USA. [Astor, Brad C.] Univ Wisconsin, Dept Populat Hlth Sci, Sch Med & Publ Hlth, Madison, WI 53706 USA. [Chodick, Gabriel] Tel Aviv Univ, Div Med, Maccabi Healthcare Serv, IL-69978 Tel Aviv, Israel. [Chodick, Gabriel] Tel Aviv Univ, Sackler Fac Med, IL-69978 Tel Aviv, Israel. [Collins, Allan J.] Minneapolis Med Res Fdn Inc, Chron Dis Res Grp, Minneapolis, MN USA. [Collins, Allan J.] Univ Minnesota, Dept Med, Minneapolis, MN 55455 USA. [Djurdjev, Ognjenka] Prov Hlth Serv Author, Dept Measurement & Reporting, Vancouver, BC, Canada. [Elley, Raina] Univ Auckland, Sch Populat Hlth, Dept Gen Practice & Primary Hlth Care, Auckland 1, New Zealand. [Evans, Marie] Karolinska Inst, CLINTEC, Div Renal Med, Stockholm, Sweden. [Garg, Amit X.] Western Univ, Dept Med, Toronto, ON, Canada. [Garg, Amit X.] Western Univ, Dept Epidemiol & Biostat, Toronto, ON, Canada. [Garg, Amit X.] Inst Clin Evaluat Sci, Toronto, ON, Canada. [Hallan, Stein I.] Norwegian Univ Sci Technol, Fac Med, Dept Canc Res & Mol Med, Trondheim, Norway. [Hallan, Stein I.] St Olavs Univ Hosp, Div Nephrol, Dept Med, Trondheim, Norway. [Ito, Sadayoshi] Tohoku Univ, Sch Med, Dept Med, Div Nephrol Endocrinol & Vasc Med, Sendai, Miyagi 980, Japan. [Jee, Sun Ha] Yonsei Univ, Grad Sch Publ Hlth, Inst Hlth Promot, Dept Epidemiol & Hlth Promot, Seoul 120749, South Korea. [Kovesdy, Csaba P.] Memphis Vet Affairs Med Ctr, Memphis, TN USA. [Kovesdy, Csaba P.] Univ Tennessee, Ctr Hlth Sci, Memphis, TN 38163 USA. [Kronenberg, Florian] Med Univ Innsbruck, Div Genet Epidemiol, Dept Med Genet Mol & Clin Pharmacol, A-6020 Innsbruck, Austria. [Heerspink, Hiddo J. Lambers] Univ Groningen, Univ Med Ctr Groningen, Dept Clin Pharm & Pharmacol, NL-9700 AB Groningen, Netherlands. [Marks, Angharad] Univ Aberdeen, Div Appl Hlth Sci, Aberdeen, Scotland. [Marks, Angharad] NHS Grampian, Aberdeen, Scotland. [Nadkarni, Girish N.] Icahn Sch Med Mt Sinai, Div Nephrol, Dept Med, New York, NY 10029 USA. [Navaneethan, Sankar D.] Cleveland Clin, Div Nephrol & Hypertens, Cleveland, OH 44106 USA. [Nelson, Robert G.] NIDDK, NIH, Phoenix, AZ USA. [Titze, Stephanie] Univ Erlangen Nurnberg, Dept Hypertens & Nephrol, D-91054 Erlangen, Germany. [Stengel, Benedicte] INSERM, CESP, Villejuif, France. [Stengel, Benedicte] Univ Paris 11, UVSQ, Univ Paris Saclay, Villejuif, France. [Woodward, Mark] Univ Oxford, Nuffield Dept Populat Hlth, George Inst Global Hlth, Oxford, England. [Woodward, Mark] Univ Sydney, George Inst Global Hlth, Sydney, NSW 2006, Australia. [Iseki, Kunitoshi] Univ Hosp Ryukyus, Dialysis Unit, Nishihara, Okinawa, Japan. RP Coresh, J (reprint author), Consortium Data Coordinating Ctr, Chron Kidney Dis Prognosis, 2024 E Monument St, Baltimore, MD 21287 USA. EM ckdpc@jhmi.edu RI de Zeeuw, Dick/E-9080-2014; Woodward, Mark/D-8492-2015; Kronenberg, Florian/B-1736-2008; Stengel, Benedicte/G-5730-2015; OI de Zeeuw, Dick/0000-0003-3434-7777; Kronenberg, Florian/0000-0003-2229-1120; Marks, Angharad/0000-0003-1910-462X; Grams, Morgan/0000-0002-4430-6023; Kalantar-Zadeh, Kamyar/0000-0002-8666-0725 FU US National Kidney Foundation; AbbVie; Amgen; Merck; National Institute of Diabetes and Digestive and Kidney Diseases [RO1D1000446-01, K08DK092287] FX The CKD-PC Data Coordinating Center is funded in part by a program grant from the US National Kidney Foundation (NKF funding sources include AbbVie, Amgen, and Merck) and grant RO1D1000446-01 from the National Institute of Diabetes and Digestive and Kidney Diseases. Dr Grams is supported by grant K08DK092287 from the National Institute of Diabetes and Digestive and Kidney Diseases. A variety of sources have supported enrollment and data collection including laboratory measurements, and follow-up in the collaborating cohorts of the CKD-PC. These funding sources include government agencies such as national institutes of health and medical research councils as well as foundations and industry sponsors listed in eAppendix 4 in the Supplement. NR 42 TC 27 Z9 27 U1 4 U2 13 PU AMER MEDICAL ASSOC PI CHICAGO PA 330 N WABASH AVE, STE 39300, CHICAGO, IL 60611-5885 USA SN 0098-7484 EI 1538-3598 J9 JAMA-J AM MED ASSOC JI JAMA-J. Am. Med. Assoc. PD JAN 12 PY 2016 VL 315 IS 2 BP 164 EP 174 DI 10.1001/jama.2015.18202 PG 11 WC Medicine, General & Internal SC General & Internal Medicine GA DA6XO UT WOS:000367949200018 PM 26757465 ER PT J AU Jonsson, H Olafsdottir, S Sigurdardottir, S Aspelund, T Eiriksdottir, G Sigurdsson, S Harris, TB Launer, L Gudnason, V AF Jonsson, Helgi Olafsdottir, Sigurbjorg Sigurdardottir, Solveig Aspelund, Thor Eiriksdottir, Gudny Sigurdsson, Sigurdur Harris, Tamara B. Launer, Lenore Gudnason, Vilmundur TI Incidence and prevalence of total joint replacements due to osteoarthritis in the elderly: risk factors and factors associated with late life prevalence in the AGES-Reykjavik Study SO BMC MUSCULOSKELETAL DISORDERS LA English DT Article DE Osteoarthritis; Arthroplasty; Epidemiology; Risk factors ID GENE/ENVIRONMENT SUSCEPTIBILITY-REYKJAVIK; HAND OSTEOARTHRITIS; KNEE OSTEOARTHRITIS; PROSPECTIVE COHORT; HIP REPLACEMENTS; ARTHROPLASTY; PROGRESSION; DISEASE AB Background: Total joint replacements (TJRs) should be considered as one of few definite endpoints in osteoarthritis research. We analyzed factors associated with late-life prevalence and risk factors for incidence of TJRs due to osteoarthritis in a population based cohort. Methods: After exclusion of inflammatory arthritis and fractures as causes of TJR, 5170 participants in the AGES-Reykjavik Study (mean age (SD) 76.4(6), 58 % females) were included for osteoarthritis studies. Three thousand one hundred thirty-three of them had a follow-up visit 5 years later. Results: The prevalence of having at least one joint replacement operation due to OA was 13.6 % and the yearly incidence was 1.4 %/year during the five-year follow-up. Factors positively associated with late life prevalence of TJR included BMI, hand OA severity, female gender, finger length ratio and spine BMD. Risk factors for TJRs in the incidence group were symptoms at initial visit, prior TJR in the contralateral joint and BMI. Much stronger associations were seen for TKR than for THR with discriminatory analysis showing an AUC 0.71 for late life prevalence and 0.84 for the incidence. Conclusions: This study illustrates the importance of the different information expressed by late life prevalence vs. incidence on the factors associated with severe osteoarthritis of the knee and hip. The observation that prior TJR is a risk factor for subsequent TJR in the contralateral joint has not been described previously. The high power predictions for TKR suggest that a predictive model may be feasible, particularly if it can be extended by the addition of further predictive variables, perhaps through genetic, biomarker or imaging data. C1 [Jonsson, Helgi] Univ Iceland, Landspitalinn Univ Hosp, Reykjavik, Iceland. [Olafsdottir, Sigurbjorg; Sigurdardottir, Solveig; Aspelund, Thor; Gudnason, Vilmundur] Univ Iceland, Reykjavik, Iceland. [Aspelund, Thor; Eiriksdottir, Gudny; Sigurdsson, Sigurdur; Gudnason, Vilmundur] Iceland Heart Assoc, Kopavogur, Iceland. [Harris, Tamara B.; Launer, Lenore] NIA, Bethesda, MD 20892 USA. [Jonsson, Helgi] Landspitalinn Univ Hosp, Dept Rheumatol, IS-108 Reykjavik, Iceland. RP Jonsson, H (reprint author), Univ Iceland, Landspitalinn Univ Hosp, Reykjavik, Iceland. EM helgi@hi.is FU NIH [N01-AG-12100]; NIA Intramural Research Program; Hjartavernd (the Icelandic Heart Association); Althingi (the Icelandic Parliament); Icelandic Osteoarthritis Fund; University of Iceland Research Fund FX The Age, Gene/Environment Susceptibility Reykjavik Study (AGES-Reykjavik) has been funded by NIH contract N01-AG-12100, the NIA Intramural Research Program, Hjartavernd (the Icelandic Heart Association), and the Althingi (the Icelandic Parliament), the Icelandic Osteoarthritis Fund and the University of Iceland Research Fund. The researchers are indebted to the participants for their willingness to participate in the study. NR 30 TC 1 Z9 1 U1 1 U2 2 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1471-2474 J9 BMC MUSCULOSKEL DIS JI BMC Musculoskelet. Disord. PD JAN 12 PY 2016 VL 17 AR 14 DI 10.1186/s12891-016-0864-7 PG 8 WC Orthopedics; Rheumatology SC Orthopedics; Rheumatology GA DA5XD UT WOS:000367875000006 PM 26759053 ER PT J AU Li, YQ Shrestha, YB Chen, M Chanturiya, T Gavrilova, O Weinstein, LS AF Li, Yong-Qi Shrestha, Yogendra B. Chen, Min Chanturiya, Tatyana Gavrilova, Oksana Weinstein, Lee S. TI G(s)alpha deficiency in adipose tissue improves glucose metabolism and insulin sensitivity without an effect on body weight SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE G proteins; adipocyte; insulin sensitivity; lipid metabolism; brown adipose tissue ID DIET-INDUCED THERMOGENESIS; ACID-BINDING PROTEIN; BROWN ADIPOSE; INDUCED OBESITY; NEONATAL SYMPATHECTOMY; ENERGY-EXPENDITURE; WHITE FAT; MICE; RESISTANCE; ADIPOCYTES AB G(s)alpha, the G protein that transduces receptor-stimulated cAMP generation, mediates sympathetic nervous system stimulation of brown adipose tissue (BAT) thermogenesis and browning of white adipose tissue (WAT), which are both potential targets for treating obesity, as well as lipolysis. We generated a mouse line with Gsa deficiency in mature BAT and WAT adipocytes (Ad-GsKO). Ad-GsKO mice had impaired BAT function, absent browning of WAT, and reduced lipolysis, and were therefore cold-intolerant. Despite the presence of these abnormalities, Ad-GsKO mice maintained normal energy balance on both standard and high-fat diets, associated with decreases in both lipolysis and lipid synthesis. In addition, Ad-GsKO mice maintained at thermoneutrality on a standard diet also had normal energy balance. Ad-GsKO mice had improved insulin sensitivity and glucose metabolism, possibly secondary to the effects of reduced lipolysis and lower circulating fatty acid binding protein 4 levels. Gsa signaling in adipose tissues may therefore affect whole-body glucose metabolism in the absence of an effect on body weight. C1 [Li, Yong-Qi; Shrestha, Yogendra B.; Chen, Min; Weinstein, Lee S.] NIDDK, Metab Dis Branch, NIH, Bethesda, MD 20892 USA. [Chanturiya, Tatyana; Gavrilova, Oksana] NIDDK, Mouse Metab Core Lab, NIH, Bethesda, MD 20892 USA. RP Weinstein, LS (reprint author), NIDDK, Metab Dis Branch, NIH, Bethesda, MD 20892 USA. EM leew@mail.nih.gov FU National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health FX We thank M. Reitman and A. Cypess for suggestions and technical assistance. This work was supported by the Intramural Research Program of the National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health. NR 46 TC 5 Z9 5 U1 4 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 JAN 12 PY 2016 VL 113 IS 2 BP 446 EP 451 DI 10.1073/pnas.1517142113 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA DA5ZO UT WOS:000367881500060 PM 26712027 ER PT J AU Chen, JB Rahman, SA Nikolaitchik, OA Grunwald, D Sardo, L Burdick, RC Plisov, S Liang, E Tai, S Pathak, VK Hu, WS AF Chen, Jianbo Rahman, Sheikh Abdul Nikolaitchik, Olga A. Grunwald, David Sardo, Luca Burdick, Ryan C. Plisov, Sergey Liang, Edward Tai, Sheldon Pathak, Vinay K. Hu, Wei-Shau TI HIV-1 RNA genome dimerizes on the plasma membrane in the presence of Gag protein SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE retrovirus; RNA genome; Gag-RNA complex; virus assembly; RNA-binding protein ID IMMUNODEFICIENCY-VIRUS TYPE-1; SINGLE-VIRION ANALYSIS; VIRAL REPLICATION; CELL BIOLOGY; RECOMBINATION; IDENTIFICATION; PARTICLES; SIGNAL; GENE; LOOP AB Retroviruses package a dimeric genome comprising two copies of the viral RNA. Each RNA contains all of the genetic information for viral replication. Packaging a dimeric genome allows the recovery of genetic information from damaged RNA genomes during DNA synthesis and promotes frequent recombination to increase diversity in the viral population. Therefore, the strategy of packaging dimeric RNA affects viral replication and viral evolution. Although its biological importance is appreciated, very little is known about the genome dimerization process. HIV-1 RNA genomes dimerize before packaging into virions, and RNA interacts with the viral structural protein Gag in the cytoplasm. Thus, it is often hypothesized that RNAs dimerize in the cytoplasm and the RNA-Gag complex is transported to the plasma membrane for virus assembly. In this report, we tagged HIV-1 RNAs with fluorescent proteins, via interactions of RNA-binding proteins and motifs in the RNA genomes, and studied their behavior at the plasma membrane by using total internal reflection fluorescence microscopy. We showed that HIV-1 RNAs dimerize not in the cytoplasm but on the plasma membrane. Dynamic interactions occur among HIV-1 RNAs, and stabilization of the RNA dimer requires Gag protein. Dimerization often occurs at an early stage of the virus assembly process. Furthermore, the dimerization process is probably mediated by the interactions of two RNA-Gag complexes, rather than two RNAs. These findings advance the current understanding of HIV-1 assembly and reveal important insights into viral replication mechanisms. C1 [Chen, Jianbo; Rahman, Sheikh Abdul; Nikolaitchik, Olga A.; Sardo, Luca; Plisov, Sergey; Liang, Edward; Tai, Sheldon; Hu, Wei-Shau] Natl Canc Inst Frederick, Viral Recombinat Sect, HIV Dynam & Replicat Program, Frederick, MD 21702 USA. [Grunwald, David] Univ Massachusetts, Sch Med, RNA Therapeut Inst, Worcester, MA 01605 USA. [Grunwald, David] Univ Massachusetts, Sch Med, Dept Biochem & Mol Pharmacol, Worcester, MA 01605 USA. [Burdick, Ryan C.; Pathak, Vinay K.] Natl Canc Inst Frederick, HIV Dynam & Replicat Program, Viral Mutat Sect, Ft Detrick, MD 21702 USA. RP Chen, JB (reprint author), Natl Canc Inst Frederick, Viral Recombinat Sect, HIV Dynam & Replicat Program, Frederick, MD 21702 USA. EM chenjia@mail.nih.gov; wei-shau.hu@nih.gov FU National Institutes of Health, National Cancer Institute, Center for Cancer Research; Intramural AIDS Targeted Antiviral Program FX We thank Anne Arthur for expert editorial help; Eric Freed, Steve Hughes, and John Coffin for discussions and critical reading of the manuscript; and Dan Larson for the beta-globin plasmid and Localize software. This research was supported in part by the Intramural Research Program of the National Institutes of Health, National Cancer Institute, Center for Cancer Research, and by Intramural AIDS Targeted Antiviral Program grant funding (to W.-S.H. and V.K.P.). NR 31 TC 12 Z9 12 U1 3 U2 10 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD JAN 12 PY 2016 VL 113 IS 2 BP E201 EP E208 DI 10.1073/pnas.1518572113 PG 8 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA DA5ZO UT WOS:000367881500015 PM 26712001 ER PT J AU Tedbury, PR Novikova, M Ablan, SD Freed, EO AF Tedbury, Philip R. Novikova, Mariia Ablan, Sherimay D. Freed, Eric O. TI Biochemical evidence of a role for matrix trimerization in HIV-1 envelope glycoprotein incorporation SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE HIV; retrovirus; matrix; envelope; trimerization ID HUMAN-IMMUNODEFICIENCY-VIRUS; PFIZER MONKEY VIRUS; GP41 CYTOPLASMIC TAIL; TYPE-1 MATRIX; CRYSTAL-STRUCTURE; CRYOELECTRON MICROSCOPY; 3-DIMENSIONAL STRUCTURE; NUCLEOTIDE-SEQUENCE; RETROVIRAL MATRIX; ENV INCORPORATION AB The matrix (MA) domain of HIV Gag has important functions in directing the trafficking of Gag to sites of assembly and mediating the incorporation of the envelope glycoprotein (Env) into assembling particles. HIV-1 MA has been shown to form trimers in vitro; however, neither the presence nor the role of MA trimers has been documented in HIV-1 virions. We developed a cross-linking strategy to reveal MA trimers in virions of replication-competent HIV-1. By mutagenesis of trimer interface residues, we demonstrated a correlation between loss of MA trimerization and loss of Env incorporation. Additionally, we found that truncating the long cytoplasmic tail of Env restores incorporation of Env into MA trimer-defective particles, thus rescuing infectivity. We therefore propose a model whereby MA trimerization is required to form a lattice capable of accommodating the long cytoplasmic tail of HIV-1 Env; in the absence of MA trimerization, Env is sterically excluded from the assembling particle. These findings establish MA trimerization as an obligatory step in the assembly of infectious HIV-1 virions. As such, the MA trimer interface may represent a novel drug target for the development of antiretrovirals. C1 [Tedbury, Philip R.; Novikova, Mariia; Ablan, Sherimay D.; Freed, Eric O.] NCI, Virus Cell Interact Sect, HIV Dynam & Replicat Program, Ctr Canc Res, Frederick, MD 21702 USA. RP Freed, EO (reprint author), NCI, Virus Cell Interact Sect, HIV Dynam & Replicat Program, Ctr Canc Res, Frederick, MD 21702 USA. EM efreed@nih.gov OI Tedbury, Philip/0000-0001-8151-4967 FU Center for Cancer Research, National Cancer Institute, NIH; Intramural AIDS Targeted Antiviral Program FX We thank members of the E.O.F. laboratory and S. Welbourn for helpful discussion and critical review of the manuscript. The HIV-Ig was obtained through the NIH AIDS Research and Reference Reagent Program. Work in the E.O.F. laboratory is supported by the Intramural Research Program of the Center for Cancer Research, National Cancer Institute, NIH, and by the Intramural AIDS Targeted Antiviral Program. NR 51 TC 3 Z9 3 U1 3 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 JAN 12 PY 2016 VL 113 IS 2 BP E182 EP E190 DI 10.1073/pnas.1516618113 PG 9 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA DA5ZO UT WOS:000367881500013 PM 26711999 ER PT J AU Zhang, F Chen, HT Zhao, LN Liu, H Przytycka, TM Zheng, J AF Zhang, Fan Chen, Haoting Zhao, Li Na Liu, Hui Przytycka, Teresa M. Zheng, Jie TI Generalized logical model based on network topology to capture the dynamical trends of cellular signaling pathways SO BMC SYSTEMS BIOLOGY LA English DT Article; Proceedings Paper CT 14th Asia Pacific Bioinformatics Conference (APBC) CY JAN 11-13, 2016 CL San Francisco, CA DE Generalized logical model; Signaling pathways; Dynamical system; Cancer ID DEATH; CELLS AB Background: Cellular responses to extracellular perturbations require signaling pathways to capture and transmit the signals. However, the underlying molecular mechanisms of signal transduction are not yet fully understood, thus detailed and comprehensive models may not be available for all the signaling pathways. In particular, insufficient knowledge of parameters, which is a long-standing hindrance for quantitative kinetic modeling necessitates the use of parameter-free methods for modeling and simulation to capture dynamic properties of signaling pathways. Results: We present a computational model that is able to simulate the graded responses to degradations, the sigmoidal biological relationships between signaling molecules and the effects of scheduled perturbations to the cells. The simulation results are validated using experimental data of protein phosphorylation, demonstrating that the proposed model is capable of capturing the main trend of protein activities during the process of signal transduction. Compared with existing simulators, our model has better performance on predicting the state transitions of signaling networks. Conclusion: The proposed simulation tool provides a valuable resource for modeling cellular signaling pathways using a knowledge-based method. C1 [Zhang, Fan; Chen, Haoting; Liu, Hui; Zheng, Jie] Nanyang Technol Univ, Sch Comp Engn, Biomed Informat Grad Lab, Singapore 639798, Singapore. [Chen, Haoting] Columbia Univ, Dept Ind Engn & Operat Res, New York, NY 10027 USA. [Zhao, Li Na] Agcy Sci Technol & Res, Bioinformat Inst, Singapore 138671, Singapore. [Liu, Hui] Changzhou Univ, Lab Informat Management, Changzhou 213164, Jiangsu, Peoples R China. [Przytycka, Teresa M.] NIH, Natl Ctr Biotechnol Informat, Natl Lib Med, Bethesda, MD 20894 USA. [Zheng, Jie] Nanyang Technol Univ, Complex Inst, Singapore 637723, Singapore. [Zheng, Jie] Agcy Sci Technol & Res, Genome Inst Singapore, Singapore 138672, Singapore. RP Zheng, J (reprint author), Nanyang Technol Univ, Sch Comp Engn, Biomed Informat Grad Lab, Singapore 639798, Singapore.; Zheng, J (reprint author), Nanyang Technol Univ, Complex Inst, Singapore 637723, Singapore.; Zheng, J (reprint author), Agcy Sci Technol & Res, Genome Inst Singapore, Singapore 138672, Singapore. EM zhengjie@ntu.edu.sg RI Zheng, Jie/C-1356-2011 OI Zheng, Jie/0000-0001-6774-9786 FU Intramural NIH HHS NR 25 TC 2 Z9 2 U1 2 U2 7 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1752-0509 J9 BMC SYST BIOL JI BMC Syst. Biol. PD JAN 11 PY 2016 VL 10 SU 1 AR 7 DI 10.1186/s12918-015-0249-9 PG 9 WC Mathematical & Computational Biology SC Mathematical & Computational Biology GA DE6XU UT WOS:000370779000007 PM 26818802 ER PT J AU Battle, KE Bisanzio, D Gibson, HS Bhatt, S Cameron, E Weiss, DJ Mappin, B Dalrymple, U Howes, RE Hay, SI Gething, PW AF Battle, Katherine E. Bisanzio, Donal Gibson, Harry S. Bhatt, Samir Cameron, Ewan Weiss, Daniel J. Mappin, Bonnie Dalrymple, Ursula Howes, Rosalind E. Hay, Simon I. Gething, Peter W. TI Treatment-seeking rates in malaria endemic countries SO MALARIA JOURNAL LA English DT Article DE Malaria; Fever; Treatment-seeking; Care-seeking; Modelling; Plasmodium vivax; Plasmodium falciparum ID CARE-SEEKING; FEBRILE ILLNESS; HEALTH-CARE; PLASMODIUM-FALCIPARUM; EASTERN UGANDA; RURAL ETHIOPIA; BEHAVIOR; CHILDREN; HOUSEHOLD; AFRICA AB Background: The proportion of individuals who seek treatment for fever is an important quantity in understanding access to and use of health systems, as well as for interpreting data on disease incidence from routine surveillance systems. For many malaria endemic countries (MECs), treatment-seeking information is available from national household surveys. The aim of this paper was to assemble sub-national estimates of treatment-seeking behaviours and to predict national treatment-seeking measures for all MECs lacking household survey data. Methods: Data on treatment seeking for fever were obtained from Demographic and Health Surveys, Malaria Indicator Surveys and Multiple Cluster Indicator Surveys for every MEC and year that data were available. National-level social, economic and health-related variables were gathered from the World Bank as putative covariates of treatment-seeking rates. A generalized additive mixed model (GAMM) was used to estimate treatment-seeking behaviours for countries where survey data were unavailable. Two separate models were developed to predict the proportion of fever cases that would seek treatment at (1) a public health facility or (2) from any kind of treatment provider. Results: Treatment-seeking data were available for 74 MECs and modelled for the remaining 24. GAMMs found that the percentage of pregnant women receiving prenatal care, vaccination rates, education level, government health expenditure, and GDP growth were important predictors for both categories of treatment-seeking outcomes. Treatment-seeking rates, which varied both within and among regions, revealed that public facilities were not always the primary facility type used. Conclusions: Estimates of treatment-seeking rates show how health services are utilized and help correct reported malaria case numbers to obtain more accurate measures of disease burden. The assembled and modelled data demonstrated that while treatment-seeking rates have overall increased over time, access remains low in some malaria endemic regions and utilization of government services is in some areas limited. C1 [Battle, Katherine E.; Bisanzio, Donal; Gibson, Harry S.; Bhatt, Samir; Cameron, Ewan; Weiss, Daniel J.; Mappin, Bonnie; Dalrymple, Ursula; Howes, Rosalind E.; Gething, Peter W.] Univ Oxford, Dept Zool, Spatial Ecol & Epidemiol Grp, Oxford, England. [Hay, Simon I.] Univ Oxford, Wellcome Trust Ctr Human Genet, Oxford, England. [Hay, Simon I.] NIH, Fogarty Int Ctr, Bethesda, MD 20892 USA. [Hay, Simon I.] Univ Washington, Inst Hlth Metr & Evaluat, Seattle, WA 98195 USA. RP Battle, KE (reprint author), Univ Oxford, Dept Zool, Spatial Ecol & Epidemiol Grp, Tinbergen Bldg,South Parks Rd, Oxford, England. EM katherine.battle@zoo.ox.ac.uk RI Hay, Simon/F-8967-2015; OI Hay, Simon/0000-0002-0611-7272; Gething, Peter/0000-0001-6759-5449; Battle, Katherine/0000-0003-2401-2615 FU Senior Research Fellowship from the Wellcome Trust [095066]; UK Medical Research Council (MRC) [K00669X]; UK Department for International Development (DFID) [K00669X]; Bill & Melinda Gates Foundation [OPP1068048, OPP1106023] FX KEB and REH are supported by a Senior Research Fellowship from the Wellcome Trust (095066) awarded to SIH. PWG is a Career Development Fellow (#K00669X) jointly funded by the UK Medical Research Council (MRC) and the UK Department for International Development (DFID) under the MRC/DFID Concordat agreement and receives support from the Bill & Melinda Gates Foundation (#OPP1068048, #OPP1106023), which also supports SB, EC, DW, HG, BM, and UD. NR 54 TC 6 Z9 6 U1 0 U2 4 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 JAN 11 PY 2016 VL 15 AR 20 DI 10.1186/s12936-015-1048-x PG 11 WC Infectious Diseases; Parasitology; Tropical Medicine SC Infectious Diseases; Parasitology; Tropical Medicine GA DB3FZ UT WOS:000368397000001 PM 26754795 ER PT J AU Morabito, KM Erez, N Graham, BS Ruckwardt, TJ AF Morabito, Kaitlyn M. Erez, Noam Graham, Barney S. Ruckwardt, Tracy J. TI Phenotype and Hierarchy of Two Transgenic T Cell Lines Targeting the Respiratory Syncytial Virus K(d)M2(82-90) Epitope Is Transfer Dose-Dependent SO PLOS ONE LA English DT Article ID MINOR HISTOCOMPATIBILITY ANTIGENS; MOUSE MODEL; INFECTION; IMMUNOPATHOLOGY; IMMUNODOMINANCE; RESPONSES; COMPETITION; MICE AB In this study, we compared two lines of transgenic CD8+ T cells specific for the same (KM282-90)-M-d epitope of respiratory syncytial virus in the CB6F1 hybrid mouse model. Here we found that these two transgenic lines had similar in vivo abilities to control viral load after respiratory syncytial virus infection using adoptive transfer. Transfer of the TRBV13-2 line resulted in higher levels of IL-6 and MIP1-alpha in the lung than TRBV13-1 transfer. Interestingly, when large numbers of cells were co-transferred, the lines formed a hierarchy, with TRBV13-2 being immunodominant over TRBV13-1 in the mediastinal lymph node despite no identifiable difference in proliferation or apoptosis between the lines. This hierarchy was not established when lower cell numbers were transferred. The phenotype and frequency of proliferating cells were also cell transfer dose-dependent with higher percentages of CD127(lo)CD62L(lo)KLRG1(lo) and proliferating cells present when lower numbers of cells were transferred. These results illustrate the importance of cell number in adoptive transfer experiments and its influence on the phenotype and hierarchy of the subsequent T cell response. C1 [Morabito, Kaitlyn M.; Erez, Noam; Graham, Barney S.; Ruckwardt, Tracy J.] NIAID, Vaccine Res Ctr, NIH, Bethesda, MD 20892 USA. [Morabito, Kaitlyn M.] Georgetown Univ, Med Ctr, Dept Microbiol & Immunol, Washington, DC 20007 USA. [Erez, Noam] Israel Inst Biol Res, Dept Infect Dis, Ness Ziona, Israel. RP Ruckwardt, TJ (reprint author), NIAID, Vaccine Res Ctr, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA. EM truckwardt@mail.nih.gov FU National Institute of Allergy and Infectious Diseases FX This work was supported by intramural funding from the National Institute of Allergy and Infectious Diseases. NR 22 TC 0 Z9 0 U1 0 U2 0 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA SN 1932-6203 J9 PLOS ONE JI PLoS One PD JAN 11 PY 2016 VL 11 IS 1 AR e0146781 DI 10.1371/journal.pone.0146781 PG 15 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA DA6CA UT WOS:000367888100153 PM 26752171 ER PT J AU Liu, HS Shi, HL Huang, F Peterson, KE Wu, H Lan, YY Zhang, BB He, YX Woods, T Du, M Wu, XJ Wang, ZT AF Liu, Hong-Shuai Shi, Hai-Lian Huang, Fei Peterson, Karin E. Wu, Hui Lan, Yun-Yi Zhang, Bei-Bei He, Yi-Xin Woods, Tyson Du, Min Wu, Xiao-Jun Wang, Zheng-Tao TI Astragaloside IV inhibits microglia activation via glucocorticoid receptor mediated signaling pathway SO SCIENTIFIC REPORTS LA English DT Article ID EXPERIMENTAL AUTOIMMUNE ENCEPHALOMYELITIS; INDUCED DIABETIC-RATS; NITRIC-OXIDE; MOLECULAR-MECHANISMS; MULTIPLE-SCLEROSIS; ENDOTHELIAL-CELLS; RADIX-ASTRAGALI; STREPTOZOTOCIN; INFLAMMATION; MICE AB Inhibition of microglia activation may provide therapeutic treatment for many neurodegenerative diseases. Astragaloside IV (ASI) with anti-inflammatory properties has been tested as a therapeutic drug in clinical trials of China. However, the mechanism of ASI inhibiting neuroinflammation is unknown. In this study, we showed that ASI inhibited microglia activation both in vivo and in vitro. It could enhance glucocorticoid receptor (GR)-luciferase activity and facilitate GR nuclear translocation in microglial cells. Molecular docking and TR-FRET GR competitive binding experiments demonstrated that ASI could bind to GR in spite of relative low affinity. Meanwhile, ASI modulated GR-mediated signaling pathway, including dephosphorylation of PI3K, Akt, I kappa B and NF kappa B, therefore, decreased downstream production of proinflammatory mediators. Suppression of microglial BV-2 activation by ASI was abrogated by GR inhibitor, RU486 or GR siRNA. Similarly, RU486 counteracted the alleviative effect of ASI on microgliosis and neuronal injury in vivo. Our findings demonstrated that ASI inhibited microglia activation at least partially by activating the glucocorticoid pathway, suggesting its possible therapeutic potential for neuroinflammation in neurological diseases. C1 [Liu, Hong-Shuai; Shi, Hai-Lian; Huang, Fei; Wu, Hui; Lan, Yun-Yi; Zhang, Bei-Bei; He, Yi-Xin; Wu, Xiao-Jun; Wang, Zheng-Tao] Shanghai Univ Tradit Chinese Med, Inst Chinese Mat Med, Key Lab Standardizat Chinese Med, Shanghai Key Lab Complex Prescript,MOE, Shanghai 201203, Peoples R China. [Peterson, Karin E.; Woods, Tyson] NIAID, Persistent Viral Dis Lab, Rocky Mt Labs, Hamilton, MT 59840 USA. [Du, Min] Chinese Acad Sci, Inst Pasteur Shanghai, Key Lab Mol Virol & Immunol, Unit Immune Signaling & Regulat, Shanghai 200030, Peoples R China. RP Du, M (reprint author), Chinese Acad Sci, Inst Pasteur Shanghai, Key Lab Mol Virol & Immunol, Unit Immune Signaling & Regulat, Shanghai 200030, Peoples R China. EM mindu@ips.ac.cn; xiaojunwu320@126.com RI Peterson, Karin/D-1492-2016 OI Peterson, Karin/0000-0003-4177-7249 FU Key Project from Department of Education of China [20123107130002]; National Natural Science Foundation of China [31270917]; Key Research Innovation Project [13ZZ099]; Shanghai Eastern Scholar Program [2013-59]; Educational Commission of Shanghai of China [2013JW20]; Shanghai E-research Institute of Bioactive Constituent in TCM plan FX This work was financially supported by Key Project from Department of Education of China (20123107130002), National Natural Science Foundation of China (31270917), Key Research Innovation Project (13ZZ099), Shanghai Eastern Scholar Program (2013-59), Educational Commission of Shanghai of China (2013JW20), and Shanghai E-research Institute of Bioactive Constituent in TCM plan. NR 44 TC 2 Z9 2 U1 1 U2 14 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 JAN 11 PY 2016 VL 6 DI 10.1038/srep19137 PG 14 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA DA9DS UT WOS:000368108800001 PM 26750705 ER PT J AU Apolo, AB Infante, JR Hamid, O Patel, MR Wang, D Kelly, K Mega, AE Britten, CD Mita, AC Ravaud, A Cuillerot, JM von Heydebreck, A Gulley, JL AF Apolo, Andrea B. Infante, Jeffrey R. Hamid, Omid Patel, Manish R. Wang, Ding Kelly, Karen Mega, Anthony E. Britten, Carolyn D. Mita, Alain C. Ravaud, Alain Cuillerot, Jean-Marie von Heydebreck, Anja Gulley, James L. TI Safety, clinical activity, and PD-L1 expression of avelumab (MSB0010718C), an anti-PD-L1 antibody, in patients with metastatic urothelial carcinoma from the JAVELIN Solid Tumor phase Ib trial. SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT Genitourinary Cancers Symposium CY JAN 07-09, 2016 CL San Francisco, CA C1 NCI, Genitourinary Malignancies Branch, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. Tennessee Oncol PLLC, Sarah Cannon Res Inst, Nashville, TN USA. Angeles Clin & Res Inst, Los Angeles, CA USA. Florida Canc Specialists, Sarah Cannon Res Inst, Sarasota, FL USA. Henry Ford Hosp, Detroit, MI 48202 USA. Univ Calif Davis, Ctr Comprehens Canc, Sacramento, CA USA. Brown Univ, Warren Alpert Med Sch, Providence, RI 02912 USA. Med Univ S Carolina, Charleston, SC 29425 USA. Cedars Sinai Med Ctr, Samuel Oschin Comprehens Canc Inst, Los Angeles, CA 90048 USA. CHU Bordeaux, Hop St Andre, Bordeaux, France. EMD Serono, Billerica, MA USA. Merck KGaA, Darmstadt, Germany. NCI, NIH, Bethesda, MD 20892 USA. RI Gulley, James/K-4139-2016 OI Gulley, James/0000-0002-6569-2912 NR 0 TC 7 Z9 7 U1 0 U2 2 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X EI 1527-7755 J9 J CLIN ONCOL JI J. Clin. Oncol. PD JAN 10 PY 2016 VL 34 IS 2 SU S MA 367 PG 1 WC Oncology SC Oncology GA DO9LW UT WOS:000378109100364 ER PT J AU Bi, X Zhao, SM Adeniran, A Kluger, HM Xie, ZQ Nawaf, C Merino, MJ Valera, V Pantuck, AJ Said, JW Belldegrun, AS Lifton, RP Shuch, BM AF Bi, Xiao Zhao, Siming Adeniran, Adebowale Kluger, Harriet M. Xie, Zuoquan Nawaf, Cayce Merino, Maria J. Valera, Vladimir Pantuck, Allan J. Said, Jonathan W. Belldegrun, Arie S. Lifton, Richard P. Shuch, Brian M. TI Genomic characterization of sarcomatoid transformation in clear cell renal cell carcinoma. SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT Genitourinary Cancers Symposium CY JAN 07-09, 2016 CL San Francisco, CA C1 Yale Univ, Sch Med, New Haven, CT USA. Yale New Haven Med Ctr, 20 York St, New Haven, CT 06504 USA. NCI, Pathol Lab, NIH, Bldg 10, Bethesda, MD 20892 USA. New York Med Coll, Vladimir, CT USA. Univ Calif Los Angeles, David Geffen Sch Med, Inst Urol Oncol, Los Angeles, CA 90095 USA. Univ Calif Los Angeles, David Geffen Sch Med, Los Angeles, CA 90095 USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X EI 1527-7755 J9 J CLIN ONCOL JI J. Clin. Oncol. PD JAN 10 PY 2016 VL 34 IS 2 SU S MA 509 PG 1 WC Oncology SC Oncology GA DO9LW UT WOS:000378109100502 ER PT J AU Frye, TP Abboud, SF Ho, R Fascelli, M Chelluri, R George, AK Choyke, PL Turkbey, B Wood, BJ Pinto, PA AF Frye, Thomas P. Abboud, Steven F. Ho, Richard Fascelli, Michele Chelluri, Raju George, Arvin Koruthu Choyke, Peter L. Turkbey, Baris Wood, Bradford J. Pinto, Peter A. TI Expanded criteria in men on active surveillance monitored by MRI-TRUS fusion biopsy. SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT Genitourinary Cancers Symposium CY JAN 07-09, 2016 CL San Francisco, CA C1 NCI, Urol Oncol Branch, NIH, Bethesda, MD 20892 USA. NIH, Bldg 10, Bethesda, MD 20892 USA. NCI, Mol Imaging Program, NIH, Bethesda, MD 20892 USA. NCI, NIH, Bethesda, MD 20892 USA. NCI, Ctr Intervent Oncol, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X EI 1527-7755 J9 J CLIN ONCOL JI J. Clin. Oncol. PD JAN 10 PY 2016 VL 34 IS 2 SU S MA 115 PG 1 WC Oncology SC Oncology GA DO9LW UT WOS:000378109100115 ER PT J AU Harmon, S Perk, T Eickhoff, JC Staab, MJ Choyke, PL Dahut, WL Apolo, AB Humm, J Larson, SM Morris, MJ Perlman, S Liu, G Jeraj, R AF Harmon, Stephanie Perk, Tim Eickhoff, Jens C. Staab, Mary Jane Choyke, Peter L. Dahut, William L. Apolo, Andrea B. Humm, John Larson, Steven M. Morris, Michael J. Perlman, Scott Liu, Glenn Jeraj, Robert TI [F-18] NaF PET/CT imaging biomarkers of progression-free survival in metastatic prostate cancer. SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT Genitourinary Cancers Symposium CY JAN 07-09, 2016 CL San Francisco, CA C1 Univ Wisconsin, Madison, WI USA. Univ Wisconsin, Dept Biostat, Madison, WI USA. Univ Wisconsin, Carbone Canc Ctr, Madison, WI USA. NCI, Mol Imaging Program, NIH, Bethesda, MD 20892 USA. NCI, NIH, Bethesda, MD 20892 USA. NCI, Genitourinary Malignancies Branch, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. Mem Sloan Kettering Canc Ctr, 1275 York Ave, New York, NY 10021 USA. Weill Cornell Med Coll, New York, NY USA. Univ Wisconsin, Dept Radiol, Madison, WI 53706 USA. Univ Wisconsin, Dept Med Phys, 1530 Med Sci Ctr, Madison, WI 53706 USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X EI 1527-7755 J9 J CLIN ONCOL JI J. Clin. Oncol. PD JAN 10 PY 2016 VL 34 IS 2 SU S MA 277 PG 1 WC Oncology SC Oncology GA DO9LW UT WOS:000378109100276 ER PT J AU Harshman, LC Kaag, M Efstathiou, JA Apolo, AB Hoffman-Censits, JH Stadler, WM Yu, EY Bochner, BH Skinner, EC Downs, T Kiltie, AE Bajorin, DF Guru, K Shipley, WU Steinberg, GD Hahn, NM Sridhar, SS AF Harshman, Lauren Christine Kaag, Matthew Efstathiou, Jason A. Apolo, Andrea B. Hoffman-Censits, Jean H. Stadler, Walter Michael Yu, Evan Y. Bochner, Bernard H. Skinner, Eila C. Downs, Tracy Kiltie, Anne E. Bajorin, Dean F. Guru, Khurshid Shipley, William U. Steinberg, Gary D. Hahn, Noah M. Sridhar, Srikala S. TI Exploring multidisciplinary practice patterns in the management of muscle invasive bladder cancer (MIBC) across the US and Canada in 2015. SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT Genitourinary Cancers Symposium CY JAN 07-09, 2016 CL San Francisco, CA C1 Dana Farber Canc Inst, Boston, MA 02115 USA. Penn State Milton S Hershey Med Ctr, Hershey, PA USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. NCI, Genitourinary Malignancies Branch, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. Thomas Jefferson Univ, Sidney Kimmel Canc Ctr, Philadelphia, PA 19107 USA. Univ Chicago, Chicago, IL 60637 USA. Fred Hutchinson Canc Res Ctr, 1124 Columbia St, Seattle, WA 98104 USA. Mem Sloan Kettering Canc Ctr, 1275 York Ave, New York, NY 10021 USA. Stanford Univ, Sch Med, Stanford, CA 94305 USA. Univ Wisconsin, Madison, WI USA. Gray Inst Radiat Oncol & Biol, Oxford, England. Roswell Pk Canc Inst, Buffalo, NY 14263 USA. Univ Chicago, Pritzker Sch Med, Dept Surg, Urol Sect, Chicago, IL 60637 USA. Johns Hopkins Univ, Sch Med, Baltimore, MD USA. Princess Margaret Canc Ctr, Toronto, ON, Canada. NR 0 TC 0 Z9 0 U1 1 U2 1 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X EI 1527-7755 J9 J CLIN ONCOL JI J. Clin. Oncol. PD JAN 10 PY 2016 VL 34 IS 2 SU S MA 368 PG 1 WC Oncology SC Oncology GA DO9LW UT WOS:000378109100365 ER PT J AU Kadakia, M George, AK Siddiqui, M Rais-Bahraini, S Rastinehad, A Vourganti, S Fascelli, M Kongnyuy, M Muthigi, A Sidana, A Frye, TP Kilchevsky, A Nix, J Yarlagadda, VK Su, D Merino, MJ Wood, BJ Choyke, PL Turkbey, IB Pinto, PA AF Kadakia, Meet George, Arvin Koruthu Siddiqui, Minhaj Rais-Bahraini, Soroush Rastinehad, Ardeshir Vourganti, Srinivas Fascelli, Michele Kongnyuy, Michael Muthigi, Akhil Sidana, Abhinav Frye, Thomas P. Kilchevsky, Amichai Nix, Jeffrey Yarlagadda, Vidhush K. Su, Daniel Merino, Maria J. Wood, Bradford J. Choyke, Peter L. Turkbey, Ismail B. Pinto, Peter A. TI Multi-institutional evaluation of multiparametric MRI and fusion-guided prostate biopsy in a biopsy-naive population. SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT Genitourinary Cancers Symposium CY JAN 07-09, 2016 CL San Francisco, CA C1 NCI, Urol Oncol Branch, NIH, Bethesda, MD 20892 USA. NIH, Bldg 10, Bethesda, MD 20892 USA. Hofstra North Shore LIJ Sch Med, New Hyde Pk, NY USA. SUNY Syracuse, Syracuse, NY USA. Univ Hosp Cincinnati, Cincinnati, OH USA. Univ Alabama Birmingham, Birmingham, AL USA. NCI, Bethesda, MD 20892 USA. NCI, Pathol Lab, NIH, Bethesda, MD 20892 USA. NCI, Ctr Intervent Onccl, NIH, Bethesda, MD 20892 USA. NCI, Mol Imaging Program, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X EI 1527-7755 J9 J CLIN ONCOL JI J. Clin. Oncol. PD JAN 10 PY 2016 VL 34 IS 2 SU S MA 60 PG 2 WC Oncology SC Oncology GA DO9LW UT WOS:000378109100060 ER PT J AU Karzai, F Madan, RA Ning, YM Theoret, MR Arlen, PM Parnes, HL Ojemuyiwa, MA Strauss, J Dawson, NA McLeod, DG Harold, N Couvillon, A Cordes, LM Chen, C Steinberg, SM Sissung, TM Price, DK Gulley, JL Figg, WD Dahut, WL AF Karzai, Fatima Madan, Ravi Amrit Ning, Yang-Min Theoret, Marc Robert Arlen, Philip M. Parnes, Howard L. Ojemuyiwa, Michelle A. Strauss, Julius Dawson, Nancy Ann McLeod, David G. Harold, Nancy Couvillon, Anna Cordes, Lisa M. Chen, Clara Steinberg, Seth M. Sissung, Tristan M. Price, Douglas K. Gulley, James L. Figg, William Douglas Dahut, William L. TI Comparison of survival of African-American (AA) patients (pts) in docetaxel (D)-based combination therapies in metastatic castrate-resistant prostate cancer (mCRPC). SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT Genitourinary Cancers Symposium CY JAN 07-09, 2016 CL San Francisco, CA C1 NCI, NIH, Bethesda, MD 20892 USA. NCI, Genitourinary Malignancies Branch, CCR, NIH, Bethesda, MD 20892 USA. US FDA, Silver Spring, MD USA. NCI, Med Oncol Branch, NIH, Bethesda, MD 20892 USA. NCI, Canc Prevent Div, NIH, Bethesda, MD 20892 USA. Walter Reed Natl Mil Med Ctr, Rockville, MD USA. Lombardi Comprehens Canc Ctr, Washington, DC USA. Walter Reed Natl Mil Med Ctr, Bethesda, MD USA. NIH, Bldg 10, Bethesda, MD 20892 USA. NIH, Dept Nucl Med, Ctr Clin, Bethesda, MD USA. NCI, Biostat & Data Management Sect, NIH, Bethesda, MD 20892 USA. NCI, Mol Pharmacol Program, NIH, Bethesda, MD 20892 USA. NCI, Genitourinary Malignancies Branch, NIH, Bethesda, MD 20892 USA. NCI, Clin Pharmacol Program, NIH, Bethesda, MD 20892 USA. RI Gulley, James/K-4139-2016; Figg Sr, William/M-2411-2016 OI Gulley, James/0000-0002-6569-2912; NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X EI 1527-7755 J9 J CLIN ONCOL JI J. Clin. Oncol. PD JAN 10 PY 2016 VL 34 IS 2 SU S MA 272 PG 2 WC Oncology SC Oncology GA DO9LW UT WOS:000378109100271 ER PT J AU Kongnyuy, M George, AK Iyer, A Frye, TP Kilchevsky, A Sidana, A Krane, S Kadakia, M Muthigi, A Mertan, F Chelluri, R Ho, R Su, D Merino, MJ Turkbey, B Choyke, PL Wood, BJ Pinto, PA AF Kongnyuy, Michael George, Arvin Koruthu Iyer, Amogh Frye, Thomas P. Kilchevsky, Amichai Sidana, Abhinav Krane, Spencer Kadakia, Meet Muthigi, Akhil Mertan, Francesca Chelluri, Raju Ho, Richard Su, Daniel Merino, Maria J. Turkbey, Baris Choyke, Peter L. Wood, Bradford J. Pinto, Peter A. TI Tumor contact length: A novel multiparametric MRI predictor of prostate cancer outcomes. SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT Genitourinary Cancers Symposium CY JAN 07-09, 2016 CL San Francisco, CA C1 NCI, Urol Oncol Branch, NIH, Bethesda, MD 20892 USA. NCI, Mol Imaging Program, NIH, Bethesda, MD 20892 USA. NCI, Bethesda, MD 20892 USA. NCI, Pathol Lab, NIH, Bldg 10, Bethesda, MD 20892 USA. NCI, NIH, Bethesda, MD 20892 USA. NCI, Ctr Intervent Oncol, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X EI 1527-7755 J9 J CLIN ONCOL JI J. Clin. Oncol. PD JAN 10 PY 2016 VL 34 IS 2 SU S MA 61 PG 2 WC Oncology SC Oncology GA DO9LW UT WOS:000378109100061 ER PT J AU Kothari, S Gustafson, D Killian, K Costello, J Edelman, DC Walling, J Meltzer, PS Theodorescu, D Apolo, AB AF Kothari, Shalin Gustafson, Daniel Killian, Keith Costello, James Edelman, Daniel C. Walling, Jennifer Meltzer, Paul S. Theodorescu, Dan Apolo, Andrea B. TI COXEN prediction of antineoplastic drug sensitivity in bladder cancer patients SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT Genitourinary Cancers Symposium CY JAN 07-09, 2016 CL San Francisco, CA C1 SUNY Upstate Med Univ, Syracuse, NY 13210 USA. Colorado State Univ, Ft Collins, CO 80523 USA. NCI, Bethesda, MD 20892 USA. Univ Colorado Anschutz Med Campus, Aurora, CO USA. Ctr Canc Res, Bethesda, MD USA. Univ Virginia, Charlottesville, VA USA. NCI, Genitourinary Malignancies Branch, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X EI 1527-7755 J9 J CLIN ONCOL JI J. Clin. Oncol. PD JAN 10 PY 2016 VL 34 IS 2 SU S MA 365 PG 1 WC Oncology SC Oncology GA DO9LW UT WOS:000378109100363 ER PT J AU Krane, LS Railkar, R Hsu, I Vocke, C Meltzer, PS Thomas, C Ferrer, M Agarwal, PK AF Krane, Louis Spencer Railkar, Reema Hsu, Iawan Vocke, Cathy Meltzer, Paul S. Thomas, Craig Ferrer, Marc Agarwal, Piyush K. TI High throughput screening to assess urothelial cancer lines and their metastatic derivatives for assessing changes in sensitivity in therapeutics SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT Genitourinary Cancers Symposium CY JAN 07-09, 2016 CL San Francisco, CA C1 Wake Forest Baptist Hlth, Winston Salem, NC USA. NCI, Bethesda, MD 20892 USA. NCI, Urol Oncol Branch, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. Ctr Canc Res, Bethesda, MD USA. NIH, Urol Oncol Branch, NCI, Bldg 10, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X EI 1527-7755 J9 J CLIN ONCOL JI J. Clin. Oncol. PD JAN 10 PY 2016 VL 34 IS 2 SU S MA 407 PG 1 WC Oncology SC Oncology GA DO9LW UT WOS:000378109100401 ER PT J AU Madan, RA Donahue, RN Singh, H Karzai, F Theoret, MR Heery, CR Strauss, J Harold, N Couvillon, A Marte, JL Hankin, A Grenga, I Chun, G Rosner, IL McLeod, DG Cordes, LM Figg, WD Dahut, WL Schlom, J Gulley, JL AF Madan, Ravi Amrit Donahue, Renee Nicole Singh, Harpreet Karzai, Fatima Theoret, Marc Robert Heery, Christopher Ryan Strauss, Julius Harold, Nancy Couvillon, Anna Marte, Jennifer L. Hankin, Amy Grenga, Italia Chun, Guinevere Rosner, Inger L. McLeod, David G. Cordes, Lisa M. Figg, William Douglas Dahut, William L. Schlom, Jeffrey Gulley, James L. TI Clinical and immunologic impact of short course enzalutamide without androgen deprivation therapy for biochemically recurrent prostate cancer. SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT Genitourinary Cancers Symposium CY JAN 07-09, 2016 CL San Francisco, CA C1 NCI, NIH, Bethesda, MD 20892 USA. Ctr Canc Res, Lab Tumor Immunol & Biol, Bethesda, MD USA. NCI, Genitourinary Malignancies Branch, NIH, Bethesda, MD 20892 USA. NCI, Genitourinary Malignancies Branch, CCR, NIH, Bethesda, MD 20892 USA. NCI, Bethesda, MD 20892 USA. Walter Reed Natl Mil Med Ctr, Bethesda, MD USA. Walter Reed Army Med Ctr, Washington, DC 20307 USA. NIH, Bldg 10, Bethesda, MD 20892 USA. NCI, Clin Pharmacol Program, NIH, Bethesda, MD 20892 USA. NCI, Lab Tumor Immunol & Biol, NIH, Bethesda, MD 20892 USA. RI Gulley, James/K-4139-2016; Figg Sr, William/M-2411-2016 OI Gulley, James/0000-0002-6569-2912; NR 0 TC 1 Z9 1 U1 0 U2 0 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X EI 1527-7755 J9 J CLIN ONCOL JI J. Clin. Oncol. PD JAN 10 PY 2016 VL 34 IS 2 SU S MA 214 PG 1 WC Oncology SC Oncology GA DO9LW UT WOS:000378109100214 ER PT J AU Maughan, BL Suzman, DL Nadal, RM Bassi, S Antonarakis, ES AF Maughan, Benjamin Louis Suzman, Daniel L. Nadal, Rosa Maria Bassi, Sunakshi Antonarakis, Emmanuel S. TI Optimal sequencing of enzalutamide and abiraterone in men with metastatic castration-resistant prostate cancer (mCRPC) SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT Genitourinary Cancers Symposium CY JAN 07-09, 2016 CL San Francisco, CA C1 Johns Hopkins Medcl Ctr, Baltimore, MD USA. Johns Hopkins, Baltimore, MD USA. NIH, Bldg 10, Bethesda, MD 20892 USA. Johns Hopkins Univ, Baltimore, MD USA. Johns Hopkins Univ, Sch Med, Baltimore, MD USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X EI 1527-7755 J9 J CLIN ONCOL JI J. Clin. Oncol. PD JAN 10 PY 2016 VL 34 IS 2 SU S MA 308 PG 1 WC Oncology SC Oncology GA DO9LW UT WOS:000378109100306 ER PT J AU Muthigi, A George, AK Iyer, A Kongnyuy, M Kadakia, M Chelluri, R Mertan, F Frye, TP Kilchevsky, A Sidana, A Krane, S Su, D Merino, MJ Turkbey, IB Choyke, PL Wood, BJ Pinto, PA AF Muthigi, Akhil George, Arvin Koruthu Iyer, Amogh Kongnyuy, Michael Kadakia, Meet Chelluri, Raju Mertan, Francesca Frye, Thomas P. Kilchevsky, Amichai Sidana, Abhinav Krane, Spencer Su, Daniel Merino, Maria J. Turkbey, Ismail B. Choyke, Peter L. Wood, Bradford J. Pinto, Peter A. TI Missing the mark? Prostate cancer upgrading by systematic biopsy over fusion biopsy. SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT Genitourinary Cancers Symposium CY JAN 07-09, 2016 CL San Francisco, CA C1 NCI, Urol Oncol Branch, NIH, Bethesda, MD 20892 USA. NCI, Mol Imaging Program, NIH, Bethesda, MD 20892 USA. NCI, Pathol Lab, NIH, Bldg 10, Bethesda, MD 20892 USA. NCI, Ctr Intervent Onccl, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X EI 1527-7755 J9 J CLIN ONCOL JI J. Clin. Oncol. PD JAN 10 PY 2016 VL 34 IS 2 SU S MA 62 PG 2 WC Oncology SC Oncology GA DO9LW UT WOS:000378109100062 ER PT J AU Ning, YMM Chen, C Maher, VE Xu, JX Kim, G Pazdur, R AF Ning, Yangmin M. Chen, Clara Maher, Virginia Ellen Xu, James Xunhai Kim, Geoffrey Pazdur, Richard TI Tumor progression versus bone scan "flare" in new lesions detected on early bone scans in patients with chemo-naive metastatic castration resistant prostate cancer (mCRPC) treated with placebo or enzalutamide SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT Genitourinary Cancers Symposium CY JAN 07-09, 2016 CL San Francisco, CA C1 US FDA, Silver Spring, MD USA. NIH, Dept Nucl Med, Ctr Clin, Bethesda, MD USA. US FDA, Washington, DC 20204 USA. US FDA, Ellicott City, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X EI 1527-7755 J9 J CLIN ONCOL JI J. Clin. Oncol. PD JAN 10 PY 2016 VL 34 IS 2 SU S MA 305 PG 1 WC Oncology SC Oncology GA DO9LW UT WOS:000378109100303 ER PT J AU Pili, R Quinn, DI Hammers, HJ Monk, P George, S Dorff, TB Olencki, T Shen, L Hutson, A Piekarz, R Carducci, MA AF Pili, Roberto Quinn, David I. Hammers, Hans J. Monk, Paul George, Saby Dorff, Tanya B. Olencki, Thomas Shen, Li Hutson, Alan Piekarz, Richard Carducci, Michael Anthony TI Immunomodulation by HDAC inhibition: Results from a phase II study with entinostat and high-dose Interleukin 2 in renal cell carcinoma patients (CTEP#7870). SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT Genitourinary Cancers Symposium CY JAN 07-09, 2016 CL San Francisco, CA C1 Indiana Univ, Mel & Brian Simon Canc Ctr, Indianapolis, IN 46204 USA. USC Norris Comprehens Canc Ctr, Los Angeles, CA USA. Johns Hopkins, Sidney Kimmel Comprehens Canc Ctr, Baltimore, MD USA. Ohio State Univ, Columbus, OH 43210 USA. Roswell Pk Canc Inst, Buffalo, NY 14263 USA. Univ So Calif, Norris Comprehens Canc Ctr, Los Angeles, CA USA. Ohio State Univ, Med Ctr, Columbus, OH 43210 USA. NCI, Canc Therapy Evaluat Program, NIH, Bethesda, MD 20892 USA. Johns Hopkins Univ, Sidney Kimmel Comprehens Canc Ctr, Baltimore, MD USA. NR 0 TC 1 Z9 1 U1 3 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 JAN 10 PY 2016 VL 34 IS 2 SU S MA 500 PG 1 WC Oncology SC Oncology GA DO9LW UT WOS:000378109100493 ER PT J AU Schweizer, MT Wang, H Luber, B Nadal, RM Spitz, AN Rosen, DM Cao, HY Antonarakis, ES Eisenberger, MA Carducci, MA Paller, CJ Denmeade, SR AF Schweizer, Michael Thomas Wang, Hao Luber, Brandon Nadal, Rosa Maria Spitz, Avery N. Rosen, David Marc Cao, Haiyi Antonarakis, Emmanuel S. Eisenberger, Mario A. Carducci, Michael Anthony Paller, Channing Judith Denmeade, Samuel R. TI Bipolar androgen therapy (BAT) in men with hormone sensitive (HS) prostate cancer (PC). SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT Genitourinary Cancers Symposium CY JAN 07-09, 2016 CL San Francisco, CA C1 Univ Washington, Fred Hutchinson Canc Res Ctr, Seattle, WA 98195 USA. Johns Hopkins, Sidney Kimmel Comprehens Canc Ctr, Baltimore, MD USA. NIH, Bldg 10, Bethesda, MD 20892 USA. Johns Hopkins Univ, Sidney Kimmel Comprehens Canc Ctr, Baltimore, MD USA. Johns Hopkins Univ, Sch Med, Baltimore, MD USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X EI 1527-7755 J9 J CLIN ONCOL JI J. Clin. Oncol. PD JAN 10 PY 2016 VL 34 IS 2 SU S MA 236 PG 1 WC Oncology SC Oncology GA DO9LW UT WOS:000378109100236 ER PT J AU Sonpavde, G Nagy, RJ Apolo, AB Agarwal, N Pal, SK Grivas, P Vaishampayan, UN Lanman, RB Talasaz, A AF Sonpavde, Guru Nagy, Rebecca J. Apolo, Andrea B. Agarwal, Neeraj Pal, Sumanta K. Grivas, Petros Vaishampayan, Ulka N. Lanman, Richard Burnham Talasaz, AmirAli TI Circulating cell-free DNA profiling of patients with advanced urothelial carcinoma. SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT Genitourinary Cancers Symposium CY JAN 07-09, 2016 CL San Francisco, CA C1 Univ Alabama Birmingham, Ctr Comprehens Canc, Birmingham, AL 35294 USA. Guardant Hlth Inc, Redwood City, CA USA. NCI, Genitourinary Malignancies Branch, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. Univ Utah, Huntsman Canc Inst, Salt Lake City, UT USA. City Hope Natl Med Ctr, Duarte, CA USA. Cleveland Clin, Taussig Canc Inst, Cleveland, OH 44106 USA. Wayne State Univ, Karmanos Canc Inst, Detroit, MI USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X EI 1527-7755 J9 J CLIN ONCOL JI J. Clin. Oncol. PD JAN 10 PY 2016 VL 34 IS 2 SU S MA 358 PG 1 WC Oncology SC Oncology GA DO9LW UT WOS:000378109100356 ER PT J AU Strauss, J Ahlman, M Karzai, F Heery, CR Cordes, LM McMahon, S Couvillon, A Rauckhorst, M Thomas, C Theoret, MR Marte, JL Millo, C Lindenberg, ML Turkbey, IB Choyke, PL Figg, WD Schlom, J Dahut, WL Gulley, JL Madan, RA AF Strauss, Julius Ahlman, Mark Karzai, Fatima Heery, Christopher Ryan Cordes, Lisa M. McMahon, Sheri Couvillon, Anna Rauckhorst, Myrna Thomas, Chrisa Theoret, Marc Robert Marte, Jennifer L. Millo, Corina Lindenberg, Maria Liza Turkbey, Ismail B. Choyke, Peter L. Figg, William Douglas Schlom, Jeffrey Dahut, William L. Gulley, James L. Madan, Ravi Amrit TI eAn analysis of sodium (18)f-fluoride PET/CT and prostate specific antigen (PSA) changes in men with metastatic castration resistant prostate cancer (mCRPC). SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT Genitourinary Cancers Symposium CY JAN 07-09, 2016 CL San Francisco, CA C1 NCI, NIH, Bethesda, MD 20892 USA. Natl Inst Biomed Imaging & Bioengn, NIH, Bethesda, MD USA. NIH, Bldg 10, Bethesda, MD 20892 USA. NCI, Genitourinary Malignancies Branch, CCR, NIH, Bethesda, MD 20892 USA. NIH, PET Dept, Bldg 10, Bethesda, MD 20892 USA. NCI, Mol Imaging Program, NIH, Bethesda, MD 20892 USA. NCI, Clin Pharmacol Program, NIH, Bethesda, MD 20892 USA. RI Gulley, James/K-4139-2016; Figg Sr, William/M-2411-2016 OI Gulley, James/0000-0002-6569-2912; NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X EI 1527-7755 J9 J CLIN ONCOL JI J. Clin. Oncol. PD JAN 10 PY 2016 VL 34 IS 2 SU S MA 203 PG 2 WC Oncology SC Oncology GA DO9LW UT WOS:000378109100203 ER PT J AU Beumer, JH Ding, F Tawbi, H Lin, Y Viluh, D Chatterjee, I Rinker, M Chow, SL Ivy, SP AF Beumer, Jan H. Ding, Fei Tawbi, Hussein Lin, Yan Viluh, Diana Chatterjee, Indrani Rinker, Matthew Chow, Selina L. Ivy, S. Percy TI Effect of Renal Dysfunction on Toxicity in Three Decades of Cancer Therapy Evaluation Program-Sponsored Single-Agent Phase I Studies SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article ID GLOMERULAR-FILTRATION-RATE; ORGAN DYSFUNCTION; SERUM CREATININE; WORKING GROUP; CLEARANCE; DRUGS; PHARMACOLOGY; PREDICTION AB Purpose Alterations in renal clearance of anticancer drugs can affect the occurrence of toxicities related to drug exposure. The National Cancer Institute and the US Food and Drug Administration (FDA) use different criteria to classify renal dysfunction. We examined those discrepancies and their potential association with the incidence of toxicities in patients enrolled onto Cancer Therapy Evaluation Program-sponsored single-agent phase I studies over three decades (1979 to 2010). Methods Data to estimate creatinine clearance according to the Cockcroft-Gault and Jelliffe formulas were available from 10,236 patients, and data to estimate creatinine clearance according to the six-and four-variable Modification of Diet in Renal Disease formulas were available from a subset (n = 4,084). Patients were classified according to National Cancer Institute and FDA criteria, and the rates of clinically relevant toxicities were evaluated within groups and compared among groups. Results Cockcroft-Gault estimated renal function improved over time, which may be attributed to an increase in weight of patients in the same time frame. Approximately 36% of patients enrolled onto phase I trials had mild renal dysfunction by FDA criteria. Relative to normal function, mild renal dysfunction was associated with a statistically significant but small increase in grade 3 or 4 non-hematologic toxicity and any relevant toxicities. Conclusion Patients with mild renal dysfunction by FDA criteria have routinely been enrolled onto phase I studies of antineoplastics without clinically meaningful increase in the risk of toxicity. In future oncology renal dysfunction trials based on the FDA classification, the FDA mild group may only need to be activated when the moderate and normal groups differ substantially in tolerability or pharmacokinetics. (C) 2015 by American Society of Clinical Oncology C1 [Beumer, Jan H.; Ding, Fei; Tawbi, Hussein; Lin, Yan; Chow, Selina L.] Univ Pittsburgh, Inst Canc, Room G27E,Hillman Res Pavilion,5117 Ctr Ave, Pittsburgh, PA 15213 USA. [Beumer, Jan H.] Univ Pittsburgh, Sch Pharm, Room G27E,Hillman Res Pavilion,5117 Ctr Ave, Pittsburgh, PA 15213 USA. [Beumer, Jan H.; Tawbi, Hussein] Univ Pittsburgh, Sch Med, Room G27E,Hillman Res Pavilion,5117 Ctr Ave, Pittsburgh, PA 15213 USA. [Lin, Yan] Univ Pittsburgh, Grad Sch Publ Hlth, Room G27E,Hillman Res Pavilion,5117 Ctr Ave, Pittsburgh, PA 15213 USA. [Viluh, Diana; Chatterjee, Indrani; Rinker, Matthew] Theradex, Princeton, NJ USA. [Ivy, S. Percy] NCI, Canc Therapy Evaluat Program, Bethesda, MD 20892 USA. RP Beumer, JH (reprint author), Univ Pittsburgh, Inst Canc, Room G27E,Hillman Res Pavilion,5117 Ctr Ave, Pittsburgh, PA 15213 USA.; Beumer, JH (reprint author), Univ Pittsburgh, Sch Pharm, Room G27E,Hillman Res Pavilion,5117 Ctr Ave, Pittsburgh, PA 15213 USA.; Beumer, JH (reprint author), Univ Pittsburgh, Sch Med, Room G27E,Hillman Res Pavilion,5117 Ctr Ave, Pittsburgh, PA 15213 USA. EM beumerj@gmail.com OI Beumer, Jan/0000-0002-8978-9401 FU Saladax Biomedical (Inst); AbbVie (Inst); Millennium (Inst); Spectrum Pharmaceuticals (Inst); Bristol-Myers Squibb (Inst); Novartis (Inst); Taiho Pharmaceutical (Inst) FX Saladax Biomedical (Inst), AbbVie (Inst), Millennium (Inst), Spectrum Pharmaceuticals (Inst), Bristol-Myers Squibb (Inst), Novartis (Inst), Taiho Pharmaceutical (Inst) NR 31 TC 5 Z9 5 U1 1 U2 1 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X EI 1527-7755 J9 J CLIN ONCOL JI J. Clin. Oncol. PD JAN 10 PY 2016 VL 34 IS 2 BP 110 EP + DI 10.1200/JCO.2014.59.7302 PG 15 WC Oncology SC Oncology GA DJ6MH UT WOS:000374327000006 PM 26392101 ER PT J AU Pinsky, PF AF Pinsky, Paul F. TI Definition of Specificity in a Screening Trial SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Letter C1 [Pinsky, Paul F.] NCI, Bethesda, MD 20892 USA. RP Pinsky, PF (reprint author), NCI, Bethesda, MD 20892 USA. NR 3 TC 1 Z9 1 U1 0 U2 0 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X EI 1527-7755 J9 J CLIN ONCOL JI J. Clin. Oncol. PD JAN 10 PY 2016 VL 34 IS 2 BP 198 EP + DI 10.1200/JCO.2015.62.9253 PG 2 WC Oncology SC Oncology GA DJ6MH UT WOS:000374327000020 PM 26573070 ER PT J AU Ge, ZY Quek, BL Beemon, KL Hogg, JR AF Ge, Zhiyun Quek, Bao Lin Beemon, Karen L. Hogg, J. Robert TI Polypyrimidine tract binding protein 1 protects mRNAs from recognition by the nonsense-mediated mRNA decay pathway SO ELIFE LA English DT Article ID ROUS-SARCOMA-VIRUS; EXON JUNCTION COMPLEX; GENOME-WIDE ANALYSIS; 3' UTRS; STABILITY ELEMENT; HUMAN-CELLS; CAENORHABDITIS-ELEGANS; SMG5-SMG7 HETERODIMER; UPF1 PHOSPHORYLATION; SPLICING REPRESSION AB The nonsense-mediated mRNA decay (NMD) pathway degrades mRNAs containing long 3'UTRs to perform dual roles in mRNA quality control and gene expression regulation. However, expansion of vertebrate 3'UTR functions has required a physical expansion of 3'UTR lengths, complicating the process of detecting nonsense mutations. We show that the polypyrimidine tract binding protein 1 (PTBP1) shields specific retroviral and cellular transcripts from NMD. When bound near a stop codon, PTBP1 blocks the NMD protein UPF1 from binding 3'UTRs. PTBP1 can thus mark specific stop codons as genuine, preserving both the ability of NMD to accurately detect aberrant mRNAs and the capacity of long 3'UTRs to regulate gene expression. Illustrating the wide scope of this mechanism, we use RNA-seq and transcriptome-wide analysis of PTBP1 binding sites to show that many human mRNAs are protected by PTBP1 and that PTBP1 enrichment near stop codons correlates with 3'UTR length and resistance to NMD. C1 [Ge, Zhiyun; Hogg, J. Robert] NHLBI, Biochem & Biophys Ctr, NIH, Bldg 10, Bethesda, MD 20892 USA. [Quek, Bao Lin; Beemon, Karen L.] Johns Hopkins Univ, Dept Biol, Baltimore, MD 21218 USA. RP Hogg, JR (reprint author), NHLBI, Biochem & Biophys Ctr, NIH, Bldg 10, Bethesda, MD 20892 USA. EM j.hogg@nih.gov OI , /0000-0001-7306-3908 FU National Institute of General Medical Sciences [P50 GM103297]; National Cancer Institute [RO1 CA048746]; National Heart, Lung, and Blood Institute Intramural Research Program FX National Institute of General Medical Sciences P50 GM103297 Karen L Beemon; National Cancer Institute RO1 CA048746 Karen L Beemon; National Heart, Lung, and Blood Institute Intramural Research Program J Robert Hogg NR 94 TC 13 Z9 13 U1 3 U2 10 PU ELIFE SCIENCES PUBLICATIONS LTD PI CAMBRIDGE PA SHERATON HOUSE, CASTLE PARK, CAMBRIDGE, CB3 0AX, ENGLAND SN 2050-084X J9 ELIFE JI eLife PD JAN 8 PY 2016 VL 5 AR e11155 DI 10.7554/eLife.11155 PG 25 WC Biology SC Life Sciences & Biomedicine - Other Topics GA DI9AU UT WOS:000373794600001 ER PT J AU Naufer, MN Callahan, KE Cook, PR Perez-Gonzalez, CE Williams, MC Furano, AV AF Naufer, M. Nabuan Callahan, Kathryn E. Cook, Pamela R. Perez-Gonzalez, Cesar E. Williams, Mark C. Furano, Anthony V. TI L1 retrotransposition requires rapid ORF1p oligomerization, a novel coiled coil-dependent property conserved despite extensive remodeling SO NUCLEIC ACIDS RESEARCH LA English DT Article ID HUMAN TRANSPOSABLE ELEMENT; LINE-1 RETROTRANSPOSITION; CHAPERONE ACTIVITY; RIBONUCLEOPROTEIN-PARTICLES; TRIMERIC STRUCTURE; HUMAN GENOMES; RNA-BINDING; PROTEIN; EVOLUTION; CELLS AB Detailed mechanistic understanding of L1 retrotransposition is sparse, particularly with respect to ORF1p, a coiled coil-mediated homotrimeric nucleic acid chaperone that can form tightly packed oligomers on nucleic acids. Although the coiled coil motif is highly conserved, it is uniquely susceptible to evolutionary change. Here we studied three ORF1 proteins: a modern human one (111p), its resuscitated primate ancestor (555p) and a mosaic modern protein (151p) wherein 9 of the 30 coiled coil substitutions retain their ancestral state. While 111p and 555p equally supported retrotransposition, 151p was inactive. Nonetheless, they were fully active in bulk assays of nucleic acid interactions including chaperone activity. However, single molecule assays showed that 151p trimers form stably bound oligomers on ssDNA at <1/10th the rate of the active proteins, revealing that oligomerization rate is a novel critical parameter of ORF1p activity in retrotransposition conserved for at least the last 25 Myr of primate evolution. C1 [Naufer, M. Nabuan; Williams, Mark C.] Northeastern Univ, Dept Phys, Boston, MA 02115 USA. [Callahan, Kathryn E.; Cook, Pamela R.; Perez-Gonzalez, Cesar E.; Furano, Anthony V.] NIDDK, Lab Cellular & Mol Biol, NIH, Bethesda, MD 20892 USA. [Perez-Gonzalez, Cesar E.] NEI, NIH, Bethesda, MD USA. RP Williams, MC (reprint author), Northeastern Univ, Dept Phys, Boston, MA 02115 USA.; Furano, AV (reprint author), NIDDK, Lab Cellular & Mol Biol, NIH, Bethesda, MD 20892 USA. EM mark@neu.edu; avf@helix.nih.gov OI Williams, Mark C./0000-0003-3219-376X FU National Institute of Diabetes, Digestive and Kidney Diseases; National Institutes of Health [HNK6H7, R01GM072462]; National Science Foundation [MCB-1243883] FX The Intramural Program of the National Institute of Diabetes, Digestive and Kidney Diseases; National Institutes of Health [HNK6H7 to K. E. C., P. R. C., C. E. P- G., A. V. F]; National Institutes of Health [R01GM072462 to M. C. W.]; National Science Foundation [MCB-1243883 to M. C. W.]. Funding for open access charge: National Institutes of Health [R01GM072462 to M. C. W., in part]; National Science Foundation [MCB-1243883 to M. C. W., in part]; The Intramural Program of the National Institute of Diabetes, Digestive and Kidney Diseases; National Institutes of Health [HNK6H7 to A. V. F., in part]. NR 60 TC 2 Z9 2 U1 0 U2 0 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0305-1048 EI 1362-4962 J9 NUCLEIC ACIDS RES JI Nucleic Acids Res. PD JAN 8 PY 2016 VL 44 IS 1 BP 281 EP 293 DI 10.1093/nar/gkv1342 PG 13 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA DF3RM UT WOS:000371264000031 PM 26673717 ER PT J AU Shamburek, RD Bakker-Arkema, R Shamburek, AM Freeman, LA Amar, MJ Auerbach, B Krause, BR Homan, R Adelman, SJ Collins, HL Sampson, M Wolska, A Remaley, AT AF Shamburek, Robert D. Bakker-Arkema, Rebecca Shamburek, Alexandra M. Freeman, Lita A. Amar, Marcelo J. Auerbach, Bruce Krause, Brian R. Homan, Reynold Adelman, Steve J. Collins, Heidi L. Sampson, Maureen Wolska, Anna Remaley, Alan T. TI Safety and Tolerability of ACP-501, a Recombinant Human Lecithin: Cholesterol Acyltransferase, in a Phase 1 Single-Dose Escalation Study SO CIRCULATION RESEARCH LA English DT Article DE acute coronary syndrome; cardiovascular diseases; cholesterol; cholesterol; HDL; lecithin cholesterol acyltransferase deficiency; lecithin cholesterol acyltransferase ID HIGH-DENSITY-LIPOPROTEIN; RANDOMIZED CONTROLLED-TRIAL; CORONARY-HEART-DISEASE; LECITHINCHOLESTEROL ACYLTRANSFERASE; CARDIOVASCULAR-DISEASE; HDL-CHOLESTEROL; PLASMA LECITHIN; IN-VIVO; ATHEROSCLEROSIS; TRANSPORT AB Rationale: Low high-density lipoprotein-cholesterol (HDL-C) in patients with coronary heart disease (CHD) may be caused by rate-limiting amounts of lecithin:cholesterol acyltransferase (LCAT). Raising LCAT may be beneficial for CHD, as well as for familial LCAT deficiency, a rare disorder of low HDL-C. Objective: To determine safety and tolerability of recombinant human LCAT infusion in subjects with stable CHD and low HDL-C and its effect on plasma lipoproteins. Methods and Results: A phase 1b, open-label, single-dose escalation study was conducted to evaluate safety, tolerability, pharmacokinetics, and pharmacodynamics of recombinant human LCAT (ACP-501). Four cohorts with stable CHD and low HDL-C were dosed (0.9, 3.0, 9.0, and 13.5 mg/kg, single 1-hour infusions) and followed up for 28 days. ACP-501 was well tolerated, and there were no serious adverse events. Plasma LCAT concentrations were dose-proportional, increased rapidly, and declined with an apparent terminal half-life of 42 hours. The 0.9-mg/kg dose did not significantly change HDL-C; however, 6 hours after doses of 3.0, 9.0, and 13.5 mg/kg, HDL-C was elevated by 6%, 36%, and 42%, respectively, and remained above baseline 4 days. Plasma cholesteryl esters followed a similar time course as HDL-C. ACP-501 infusion rapidly decreased small- and intermediate-sized HDL, whereas large HDL increased. Pre--HDL also rapidly decreased and was undetectable 12 hours post ACP-501 infusion. Conclusions: ACP-501 has an acceptable safety profile after a single intravenous infusion. Lipid and lipoprotein changes indicate that recombinant human LCAT favorably alters HDL metabolism and support recombinant human LCAT use in future clinical trials in CHD and familial LCAT deficiency patients. Clinical Trial Registration: URL: http://www.clinicaltrials.gov. Unique identifier: NCT01554800. C1 [Shamburek, Robert D.; Shamburek, Alexandra M.; Freeman, Lita A.; Amar, Marcelo J.; Wolska, Anna; Remaley, Alan T.] NHLBI, NIH, Bethesda, MD 20892 USA. [Bakker-Arkema, Rebecca; Auerbach, Bruce; Krause, Brian R.; Homan, Reynold] AlphaCore Pharma LLC, Ann Arbor, MI USA. [Adelman, Steve J.; Collins, Heidi L.] VascularStrategies LLC, Plymouth Meeting, PA USA. [Sampson, Maureen] NIH, Dept Lab Med, Ctr Clin, Bethesda, MD 20892 USA. RP Shamburek, RD (reprint author), NIH, 10 Ctr Dr,MSC 1666 Bldg 10 Rm,8N-202, Bethesda, MD 20892 USA. EM bobs@mail.nih.gov FU National Heart, Lung, and Blood Institute; National Institutes of Health; AlphaCore Pharma FX Research was supported by research funds from the intramural National Heart, Lung, and Blood Institute program and a National Institutes of Health - Cooperative Research and Development Agreement with AlphaCore Pharma. NR 38 TC 4 Z9 4 U1 2 U2 4 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 0009-7330 EI 1524-4571 J9 CIRC RES JI Circ.Res. PD JAN 8 PY 2016 VL 118 IS 1 BP 73 EP 82 DI 10.1161/CIRCRESAHA.115.306223 PG 10 WC Cardiac & Cardiovascular Systems; Hematology; Peripheral Vascular Disease SC Cardiovascular System & Cardiology; Hematology GA DB4AN UT WOS:000368455200012 PM 26628614 ER PT J AU Li, YY Leneghan, DB Miura, K Nikolaeva, D Brian, IJ Dicks, MDJ Fyfe, AJ Zakutansky, SE de Cassan, S Long, CA Draper, SJ Hill, AVS Hill, F Biswas, S AF Li, Yuanyuan Leneghan, Darren B. Miura, Kazutoyo Nikolaeva, Daria Brian, Iona J. Dicks, Matthew D. J. Fyfe, Alex J. Zakutansky, Sarah E. de Cassan, Simone Long, Carole A. Draper, Simon J. Hill, Adrian V. S. Hill, Fergal Biswas, Sumi TI Enhancing immunogenicity and transmission-blocking activity of malaria vaccines by fusing Pfs25 to IMX313 multimerization technology SO SCIENTIFIC REPORTS LA English DT Article ID OLIGOMERIZATION DOMAIN; ANTIBODY-RESPONSES; ADJUVANT VACCINES; RHESUS MACAQUES; PROTECTS MICE; ADENOVIRUS; STAGE; CANDIDATES; ANTIGEN; NANOPARTICLE AB Transmission-blocking vaccines (TBV) target the sexual-stages of the malaria parasite in the mosquito midgut and are widely considered to be an essential tool for malaria elimination. High-titer functional antibodies are required against target antigens to achieve effective transmission-blocking activity. We have fused Pfs25, the leading malaria TBV candidate antigen to IMX313, a molecular adjuvant and expressed it both in ChAd63 and MVA viral vectors and as a secreted protein-nanoparticle. Pfs25-IMX313 expressed from viral vectors or as a protein-nanoparticle is significantly more immunogenic and gives significantly better transmission-reducing activity than monomeric Pfs25. In addition, we demonstrate that the Pfs25-IMX313 protein-nanoparticle leads to a qualitatively improved antibody response in comparison to soluble Pfs25, as well as to significantly higher germinal centre (GC) responses. These results demonstrate that antigen multimerization using IMX313 is a very promising strategy to enhance antibody responses against Pfs25, and that Pfs25-IMX313 is a highly promising TBV candidate vaccine. C1 [Li, Yuanyuan; Leneghan, Darren B.; Nikolaeva, Daria; Brian, Iona J.; Dicks, Matthew D. J.; Fyfe, Alex J.; Zakutansky, Sarah E.; de Cassan, Simone; Draper, Simon J.; Hill, Adrian V. S.; Biswas, Sumi] Univ Oxford, Jenner Inst, Oxford OX3 7DQ, England. [Miura, Kazutoyo; Nikolaeva, Daria; Long, Carole A.] NIAID, Lab Malaria & Vector Res, NIH, Rockville, MD USA. [Hill, Fergal] IMAXIO, F-69007 Lyon, France. RP Li, YY; Leneghan, DB; Biswas, S (reprint author), Univ Oxford, Jenner Inst, Oxford OX3 7DQ, England. EM lee.li@ndm.ox.ac.uk; darren.leneghan@ndm.ox.ac.uk; sumi.biswas@ndm.ox.ac.uk OI Taylor, Iona/0000-0002-2287-9488; Draper, Simon/0000-0002-9415-1357 FU UK Medical Research Council [G1000527]; UK MRC; UK Department for International Development (DFID); National Institute of Allergy and Infectious Diseases/NIH; PATH Malaria Vaccine Initiative FX SB is a NDM Leadership Fellow and Junior Research Fellow of St Catherine's College, Oxford University. SJD and AVSH are Jenner Investigators. SJD is a Lister Institute Research Prize Fellow and a UK Medical Research Council Career Development Fellow [grant number G1000527; this Fellowship is jointly funded by the UK MRC and the UK Department for International Development (DFID) under the MRC/DFID Concordat agreement]. This study was supported in part by the intramural program of the National Institute of Allergy and Infectious Diseases/NIH, and by the PATH Malaria Vaccine Initiative. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. The authors are grateful for the assistance of Julie Furze, Andrew Blagborough, Federica Cappuccini, Anna Goodman and Alexandre Douglas, as well as the Jenner Institute Adjuvant Bank, Flow Cytometry and Viral Vector Core Facilities. NR 40 TC 4 Z9 4 U1 1 U2 4 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 2045-2322 J9 SCI REP-UK JI Sci Rep PD JAN 8 PY 2016 VL 6 AR 18848 DI 10.1038/srep18848 PG 13 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA DB7EJ UT WOS:000368677200001 PM 26743316 ER PT J AU Nai, WQ Threapleton, D Lu, JB Zhang, KW Wu, HY Fu, Y Wang, YY Ou, ZJ Shan, LL Ding, Y Yu, YL Dai, M AF Nai, Wenqing Threapleton, Diane Lu, Jingbo Zhang, Kewei Wu, Hongyuan Fu, You Wang, Yuanyuan Ou, Zejin Shan, Lanlan Ding, Yan Yu, Yanlin Dai, Meng TI Identification of novel genes and pathways in carotid atheroma using integrated bioinformatic methods SO SCIENTIFIC REPORTS LA English DT Article ID SPLEEN TYROSINE KINASE; DEFICIENT MICE; ATHEROSCLEROTIC PLAQUES; MICROARRAY ANALYSIS; EXPRESSION; NETWORKS; CELLS; INFLAMMATION; HOMEOSTASIS; BIOLOGY AB Atherosclerosis is the primary cause of cardiovascular events and its molecular mechanism urgently needs to be clarified. In our study, atheromatous plaques (ATH) and macroscopically intact tissue (MIT) sampled from 32 patients were compared and an integrated series of bioinformatic microarray analyses were used to identify altered genes and pathways. Our work showed 816 genes were differentially expressed between ATH and MIT, including 443 that were up-regulated and 373 that were down-regulated in ATH tissues. GO functional-enrichment analysis for differentially expressed genes (DEGs) indicated that genes related to the "immune response" and "muscle contraction" were altered in ATHs. KEGG pathway-enrichment analysis showed that up-regulated DEGs were significantly enriched in the "FceRI-mediated signaling pathway", while down-regulated genes were significantly enriched in the "transforming growth factor-beta signaling pathway". Protein-protein interaction network and module analysis demonstrated that VAV1, SYK, LYN and PTPN6 may play critical roles in the network. Additionally, similar observations were seen in a validation study where SYK, LYN and PTPN6 were markedly elevated in ATH. All in all, identification of these genes and pathways not only provides new insights into the pathogenesis of atherosclerosis, but may also aid in the development of prognostic and therapeutic biomarkers for advanced atheroma. C1 [Nai, Wenqing; Wu, Hongyuan; Fu, You; Wang, Yuanyuan; Ou, Zejin; Shan, Lanlan; Ding, Yan; Dai, Meng] Southern Med Univ, Dept Hlth Management, Guangzhou 510515, Guangdong, Peoples R China. [Lu, Jingbo] Southern Med Univ, Nanfang Hosp, Dept Vasc Surg, Guangzhou 510515, Guangdong, Peoples R China. [Threapleton, Diane] Chinese Univ Hong Kong, Sch Publ Hlth & Primary Care, Div Epidemiol, Hong Kong, Hong Kong, Peoples R China. [Yu, Yanlin] NCI, Lab Canc Biol & Genet, NIH, Bethesda, MD 20892 USA. [Zhang, Kewei] Zhengzhou Univ, Peoples Hosp Henan Prov, Dept Vasc Surg, Zhengzhou 450003, Henan, Peoples R China. RP Dai, M (reprint author), NCI, Lab Canc Biol & Genet, NIH, 37 Convent Dr, Bethesda, MD 20892 USA. EM yuy@mail.nih.gov; dm42298@126.com FU Science and Technology Foundation of Guangzhou city [2013J4500040] FX We sincerely thank Dr. HANENE AYARI and Dr. GIAMPIERO BRICCA for our free access to the microarray data of carotid atheroma. This work was supported by Science and Technology Foundation of Guangzhou city (Project Number: 2013J4500040). NR 48 TC 3 Z9 3 U1 4 U2 9 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 2045-2322 J9 SCI REP-UK JI Sci Rep PD JAN 8 PY 2016 VL 6 AR 18764 DI 10.1038/srep18764 PG 10 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA DB7AG UT WOS:000368666200001 PM 26742467 ER PT J AU Unger, FT Lange, N Kruger, J Compton, C Moore, H Agrawal, L Juhl, H David, KA AF Unger, Florian T. Lange, Nicole Krueger, Jana Compton, Carolyn Moore, Helen Agrawal, Lokesh Juhl, Hartmut David, Kerstin A. TI Nanoproteomic analysis of ischemia-dependent changes in signaling protein phosphorylation in colorectal normal and cancer tissue SO JOURNAL OF TRANSLATIONAL MEDICINE LA English DT Article DE Clinical biospecimen; Ischemia; NanoPro1000; Isoform phosphorylation; Clinical testing ID SQUAMOUS-CELL CARCINOMA; GENE-EXPRESSION; BREAST-CANCER; MET RECEPTOR; PATHWAY; KINASE; ACTIVATION; IMPACT; PROGNOSIS; SPECIMENS AB Background: Clinical diagnostic research relies upon the collection of tissue samples, and for those samples to be representative of the in vivo situation. Tissue collection procedures, including post-operative ischemia, can impact the molecular profile of the tissue at the genetic and proteomic level. Understanding the influence of factors such as ischemia on tissue samples is imperative in order to develop both markers of tissue quality and ultimately accurate diagnostic tests. Methods: Using NanoPro1000 technology, a rapid and highly sensitive immunoassay platform, the phosphorylation status of clinically relevant cancer-related biomarkers in response to ischemia was quantified in tissue samples from 20 patients with primary colorectal cancer. Tumor tissue and adjacent normal tissue samples were collected and subjected to cold ischemia prior to nanoproteomic analysis of AKT, ERK1/2, MEK1/2, and c-MET. Ischemia-induced relative changes in overall phosphorylation and phosphorylation of individual isoforms were calculated and statistical significance determined. Any differences in baseline levels of phosphorylation between tumor tissue and normal tissue were also analyzed. Results: Changes in overall phosphorylation of the selected proteins in response to ischemia revealed minor variations in both normal and tumor tissue; however, significant changes were identified in the phosphorylation of individual isoforms. In normal tissue post-operative ischemia, phosphorylation was increased in two AKT isoforms, two ERK1/2 isoforms, and one MEK1/2 isoform and decreased in one MEK1/2 isoform and one c-MET isoform. Following ischemia in tumor tissue, one AKT isoform showed decreased phosphorylation and there was an overall increase in unphosphorylated ERK1/2, whereas an increase in the phosphorylation of two MEK1/2 isoforms was observed. There were no changes in c-MET phosphorylation in tumor tissue. Conclusion: This study provides insight into the influence of post-operative ischemia on tissue sample biology, which may inform the future development of markers of tissue quality and assist in the development of diagnostic tests. C1 [Unger, Florian T.; Lange, Nicole; Krueger, Jana; Juhl, Hartmut; David, Kerstin A.] Indivumed GmbH, D-20251 Hamburg, Germany. [Moore, Helen; Agrawal, Lokesh] NCI, Biorepositories & Biospecimen Res Branch, NIH, Bethesda, MD 20892 USA. [Compton, Carolyn] Arizona State Univ, Phoenix, AZ USA. RP David, KA (reprint author), Indivumed GmbH, Falkenried 88, D-20251 Hamburg, Germany. EM david@indivumed.com FU Indivumed FX Medical editing services were provided by Nicola Crofts on behalf of Complete Medical Communications, funded by Indivumed. NR 34 TC 2 Z9 2 U1 0 U2 0 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 JAN 8 PY 2016 VL 14 AR 6 DI 10.1186/s12967-015-0752-1 PG 15 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA DA8LO UT WOS:000368056500001 PM 26742633 ER PT J AU Binder, AK Kosak, JP Janhardhan, KS Moser, G Eling, TE Korach, KS AF Binder, April K. Kosak, Justin P. Janhardhan, Kyathanahalli S. Moser, Glenda Eling, Thomas E. Korach, Kenneth S. TI Expression of Human NSAID Activated Gene 1 in Mice Leads to Altered Mammary Gland Differentiation and Impaired Lactation SO PLOS ONE LA English DT Article ID TGF-BETA SUPERFAMILY; FAMILY-MEMBERS; BREAST-MILK; TISSUES; GROWTH; PROGESTERONE; CONSEQUENCES; SECRETION; EXPOSURES; CYTOKINE AB Transgenic mice expressing human non-steroidal anti-inflammatory drug activated gene 1 (NAG-1) have less adipose tissue, improved insulin sensitivity, lower insulin levels and are resistant to dietary induced obesity. The hNAG-1 expressing mice are more metabolically active with a higher energy expenditure. This study investigates female reproduction in the hNAG-1 transgenicmice and finds the femalemice are fertile but have reduced pup survival after birth. Examination of the mammary glands in these mice suggests that hNAG-1 expressing mice have altered mammary epithelial development during pregnancy, including reduced occupancy of the fat pad and increased apoptosis via TUNEL positive cells on lactation day 2. Pups nursing from hNAG-1 expressing dams have reduced milk spots compared to pups nursing from WT dams. When CD-1 pups were cross-fostered with hNAG-1 or WT dams; reduced milk volume was observed in pups nursing from hNAG-1 dams compared to pups nursing from WT dams in a lactation challenge study. Milk was isolated from WT and hNAG-1 dams, and the milk was found to have secreted NAG-1 protein (approximately 25 ng/mL) from hNAG-1 dams. The WT dams had no detectable hNAG-1 in the milk. A decrease in non-esterified free fatty acids in the milk of hNAG-1 dams was observed. Altered milk composition suggests that the pups were receiving inadequate nutrients during perinatal development. To examine this hypothesis serum was isolated from pups and clinical chemistry points were measured. Male and female pups nursing from hNAG-1 dams had reduced serum triglyceride concentrations. Microarray analysis revealed that genes involved in lipid metabolism are differentially expressed in hNAG-1 mammary glands. Furthermore, the expression of Cidea/CIDEA that has been shown to regulate milk lipid secretion in the mammary gland was reduced in hNAG-1 mammary glands. This study suggests that expression of hNAG-1 in mice leads to impaired lactation and reduces pup survival due to altered milk quality and quantity. C1 [Binder, April K.; Korach, Kenneth S.] NIEHS, Reprod & Dev Biol Lab, NIH, Res Triangle Pk, NC 27709 USA. [Kosak, Justin P.; Eling, Thomas E.] NIEHS, Mol Carcinogenesis Lab, NIH, Res Triangle Pk, NC 27709 USA. [Janhardhan, Kyathanahalli S.; Moser, Glenda] Integrated Lab Syst Inc, Res Triangle Pk, NC USA. RP Korach, KS (reprint author), NIEHS, Reprod & Dev Biol Lab, NIH, POB 12233, Res Triangle Pk, NC 27709 USA. EM Korach@niehs.nih.gov OI Korach, Kenneth/0000-0002-7765-418X FU NIH, NIEHS Intramural Research Program [1ZIAES070065, Z01-ES010016-14]; Integrated Laboratory Systems Incorporated FX Funding and support was provided by NIH, NIEHS Intramural Research Program: Projects 1ZIAES070065 (KSK) and Z01-ES010016-14 (TEE). Integrated Laboratory Systems Incorporated provided support in the form of salaries for authors KSJ and GM, 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 42 TC 1 Z9 1 U1 0 U2 0 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA SN 1932-6203 J9 PLOS ONE JI PLoS One PD JAN 8 PY 2016 VL 11 IS 1 AR e0146518 DI 10.1371/journal.pone.0146518 PG 16 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA DA5AX UT WOS:000367815600057 PM 26745373 ER PT J AU Danielson, KM Estanislau, J Tigges, J Toxavidis, V Camacho, V Felton, EJ Khoory, J Kreimer, S Ivanov, AR Mantel, PY Jones, J Akuthota, P Das, S Ghiran, I AF Danielson, Kirsty M. Estanislau, Jessica Tigges, John Toxavidis, Vasilis Camacho, Virginia Felton, Edward J. Khoory, Joseph Kreimer, Simion Ivanov, Alexander R. Mantel, Pierre-Yves Jones, Jennifer Akuthota, Praveen Das, Saumya Ghiran, Ionita TI Diurnal Variations of Circulating Extracellular Vesicles Measured by Nano Flow Cytometry SO PLOS ONE LA English DT Article ID MICROPARTICLES; CELLS; EXERCISE; SYSTEM AB The identification of extracellular vesicles (EVs) as intercellular conveyors of biological information has recently emerged as a novel paradigm in signaling, leading to the exploitation of EVs and their contents as biomarkers of various diseases. However, whether there are diurnal variations in the size, number, and tissue of origin of blood EVs is currently not known, and could have significant implications when using EVs as biomarkers for disease progression. Currently available technologies for the measurement of EV size and number are either time consuming, require specialized equipment, or lack sufficient accuracy across a range of EV sizes. Flow cytometry represents an attractive alternative to these methods; however, traditional flow cytometers are only capable of measuring particles down to 500 nm, which is significantly larger than the average and median sizes of plasma EVs. Utilizing a Beckman Coulter MoFlo XDP flow cytometer with NanoView module, we employed nanoscale flow cytometry (termed nanoFCM) to examine the relative number and scatter distribution of plasma EVs at three different time points during the day in 6 healthy adults. Analysis of liposomes and plasma EVs proved that nanoFCM is capable of detecting biologically-relevant vesicles down to 100 nm in size. With this high resolution configuration, we observed variations in the relative size (FSC/SSC distributions) and concentration (proportions) of EVs in healthy adult plasma across the course of a day, suggesting that there are diurnal variations in the number and size distribution of circulating EV populations. The use of nanoFCM provides a valuable tool for the study of EVs in both health and disease; however, additional refinement of nanoscale flow cytometric methods is needed for use of these instruments for quantitative particle counting and sizing. Furthermore, larger scale studies are necessary to more clearly define the diurnal variations in circulating EVs, and thus further inform their use as biomarkers for disease. C1 [Danielson, Kirsty M.; Estanislau, Jessica; Tigges, John; Toxavidis, Vasilis; Camacho, Virginia; Felton, Edward J.; Khoory, Joseph; Mantel, Pierre-Yves; Akuthota, Praveen; Das, Saumya; Ghiran, Ionita] Beth Israel Deaconess Med Ctr, Dept Med, Boston, MA 02215 USA. [Danielson, Kirsty M.; Estanislau, Jessica; Tigges, John; Toxavidis, Vasilis; Camacho, Virginia; Felton, Edward J.; Khoory, Joseph; Mantel, Pierre-Yves; Akuthota, Praveen; Das, Saumya; Ghiran, Ionita] Harvard Univ, Sch Med, Boston, MA USA. [Kreimer, Simion; Ivanov, Alexander R.] Northeastern Univ, Barnett Inst Chem & Biol Anal, Boston, MA 02115 USA. [Kreimer, Simion; Ivanov, Alexander R.] Northeastern Univ, Dept Chem & Chem Biol, Boston, MA 02115 USA. [Jones, Jennifer] NCI, Mol Immunogenet & Vaccine Res Sect, Vaccine Branch, CCR, Bethesda, MD 20892 USA. RP Ghiran, I (reprint author), Beth Israel Deaconess Med Ctr, Dept Med, Boston, MA 02215 USA. EM ighiran@bidmc.harvard.edu RI Jones, Jennifer/C-8691-2015 OI Jones, Jennifer/0000-0002-9488-7719 FU National Institutes of Health [R01 HL096795, 1U01HL126497-01, UH2TR000901]; Bill and Melinda Gates Foundation [OPP1032683] FX This work was supported by grants from the National Institutes of Health R01 HL096795 (IG), 1U01HL126497-01 (IG), UH2TR000901 (SD) and Bill and Melinda Gates Foundation award OPP1032683 (IG). NR 21 TC 0 Z9 0 U1 1 U2 4 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA SN 1932-6203 J9 PLOS ONE JI PLoS One PD JAN 8 PY 2016 VL 11 IS 1 AR e0144678 DI 10.1371/journal.pone.0144678 PG 11 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA DA5AX UT WOS:000367815600003 PM 26745887 ER PT J AU Bakelar, J Buchanan, SK Noinaj, N AF Bakelar, Jeremy Buchanan, Susan K. Noinaj, Nicholas TI The structure of the beta-barrel assembly machinery complex SO SCIENCE LA English DT Article ID MEMBRANE PROTEIN BIOGENESIS; GRAM-NEGATIVE BACTERIA; OUTER-MEMBRANE; ESCHERICHIA-COLI; CRYSTAL-STRUCTURE; BAM COMPLEX; ESSENTIAL COMPONENT; PERIPLASMIC DOMAIN; YAET COMPLEX; FLEXIBILITY AB beta-Barrel outer membrane proteins (OMPs) are found in the outer membranes of Gram-negative bacteria and are essential for nutrient import, signaling, and adhesion. A 200-kilodalton five-component complex called the beta-barrel assembly machinery (BAM) complex has been implicated in the biogenesis of OMPs. We report the structure of the BAM complex from Escherichia coli, revealing that binding of BamCDE modulates the conformation of BamA, the central component, which may serve to regulate the BAM complex. The periplasmic domain of BamA was in a closed state that prevents access to the barrel lumen, which indicates substrate OMPs may not be threaded through the barrel during biogenesis. Further, conformational shifts in the barrel domain lead to opening of the exit pore and rearrangement at the lateral gate. C1 [Bakelar, Jeremy; Noinaj, Nicholas] Purdue Univ, Dept Biol Sci, Markey Ctr Struct Biol, W Lafayette, IN 47907 USA. [Buchanan, Susan K.] NIDDK, NIH, Bethesda, MD 20892 USA. RP Noinaj, N (reprint author), Purdue Univ, Dept Biol Sci, Markey Ctr Struct Biol, W Lafayette, IN 47907 USA. EM nnoinaj@purdue.edu FU Department of Biological Sciences at Purdue University; National Institute of Allergy and Infectious Diseases [1K22AI113078-01]; Intramural Research Program of the NIH, National Institute of Diabetes and Digestive and Kidney Diseases; Office of Basic Energy Sciences, Office of Science, U.S. Department of Energy [W-31-109-Eng-38] FX We thank H. Bernstein for providing the pJH114 plasmid. J.B. and N.N. are supported by the Department of Biological Sciences at Purdue University and by the National Institute of Allergy and Infectious Diseases (1K22AI113078-01). S.K.B. is supported by the Intramural Research Program of the NIH, National Institute of Diabetes and Digestive and Kidney Diseases. We thank the staff at the Southeast Regional Collaborative Access Team (SER-CAT) beamline at the Advanced Photon Source, Argonne National Laboratory, for their assistance during data collection. Use of the Advanced Photon Source was supported by the Office of Basic Energy Sciences, Office of Science, U.S. Department of Energy, under contract no. W-31-109-Eng-38 (SER-CAT). Coordinates and structure factors for the BamACDE complex have been deposited into the PDB with PDB ID 5EKQ. NR 34 TC 18 Z9 18 U1 4 U2 31 PU AMER ASSOC ADVANCEMENT SCIENCE PI WASHINGTON PA 1200 NEW YORK AVE, NW, WASHINGTON, DC 20005 USA SN 0036-8075 EI 1095-9203 J9 SCIENCE JI Science PD JAN 8 PY 2016 VL 351 IS 6269 BP 180 EP 186 DI 10.1126/science.aad3460 PG 7 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA DA4XQ UT WOS:000367806500044 PM 26744406 ER PT J AU Romes, EM Sobhany, M Stanley, RE AF Romes, Erin M. Sobhany, Mack Stanley, Robin E. TI The Crystal Structure of the Ubiquitin-like Domain of Ribosome Assembly Factor Ytm1 and Characterization of Its Interaction with the AAA-ATPase Midasin SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID WD-REPEAT PROTEIN; NUCLEOLAR LOCALIZATION; CELL-PROLIFERATION; BIOGENESIS FACTORS; BINDING DOMAINS; ER-ALPHA; PES1; COMPLEX; MATURATION; CANCER AB The synthesis of eukaryotic ribosomes is a complex, energetically demanding process requiring the aid of numerous non-ribosomal factors, such as the PeBoW complex. The mammalian PeBoW complex, composed of Pes1, Bop1, and WDR12, is essential for the processing of the 32S preribosomal RNA. Previous work in Saccharomyces cerevisiae has shown that release of the homologous proteins in this complex (Nop7, Erb1, and Ytm1, respectively) from preribosomal particles requires Rea1 (midasin or MDN1 in humans), a large dynein-like protein. Midasin contains a C-terminal metal ion-dependent adhesion site (MIDAS) domain that interacts with the N-terminal ubiquitin- like (UBL) domain of Ytm1/WDR12 as well as the UBL domain of Rsa4/Nle1 in a later step in the ribosome maturation pathway. Here we present the crystal structure of the UBL domain of the WDR12 homologue from S. cerevisiae at 1.7 angstrom resolution and demonstrate that human midasin binds to WDR12 as well as Nle1 through their respective UBL domains. Midasin contains a well conserved extension region upstream of the MIDAS domain required for binding WDR12 and Nle1, and the interaction is dependent upon metal ion coordination because removal of the metal or mutation of residues that coordinate the metal ion diminishes the interaction. Mammalian WDR12 displays prominent nucleolar localization that is dependent upon active ribosomal RNA transcription. Based upon these results, we propose that release of the PeBoW complex and subsequent release of Nle1 by midasin is a well conserved step in the ribosome maturation pathway in both yeast and mammalian cells. C1 [Romes, Erin M.; Sobhany, Mack; Stanley, Robin E.] NIEHS, Signal Transduct Lab, NIH, Dept Hlth & Human Serv, Res Triangle Pk, NC 27709 USA. RP Stanley, RE (reprint author), NIEHS, Signal Transduct Labo, NIH, Bldg 101,Rm F378,111 TW Alexander Dr, Res Triangle Pk, NC 27709 USA. EM robin.stanley@nih.gov FU NIEHS, National Institutes of Health; United States Department of Energy, Office of Science, Office of Basic Energy Sciences [W-31-109-Eng-38] FX This work was supported in whole or in part by the Intramural Research Program of NIEHS, National Institutes of Health. 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. The authors declare that they have no conflicts of interest with the contents of this article. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. NR 56 TC 1 Z9 1 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 JAN 8 PY 2016 VL 291 IS 2 BP 882 EP 893 DI 10.1074/jbc.M115.693259 PG 12 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA DA5GF UT WOS:000367830500034 PM 26601951 ER PT J AU Graham, HK Rosenbaum, P Paneth, N Dan, B Lin, JP Damiano, DL Becher, JG Gaebler-Spira, D Colver, A Reddihough, D Crompton, KE Lieber, RL AF Graham, H. Kerr Rosenbaum, Peter Paneth, Nigel Dan, Bernard Lin, Jean-Pierre Damiano, Diane L. Becher, Jules G. Gaebler-Spira, Deborah Colver, Allan Reddihough, DinahS. Crompton, Kylie E. Lieber, Richard L. TI Cerebral palsy SO NATURE REVIEWS DISEASE PRIMERS LA English DT Article ID QUALITY-OF-LIFE; EVENT MULTILEVEL SURGERY; RANDOMIZED CONTROLLED-TRIAL; AUTOLOGOUS CORD BLOOD; GROSS MOTOR FUNCTION; FUNCTION CLASSIFICATION-SYSTEM; PREVENT HIP DISPLACEMENT; CHILD NEUROLOGY SOCIETY; BOTULINUM-TOXIN-A; NECK-SHAFT ANGLE AB Cerebral palsy is the most common cause of childhood-onset, lifelong physical disability in most countries, affecting about 1 in 500 neonates with an estimated prevalence of 17 million people worldwide. Cerebral palsy is not a disease entity in the traditional sense but a clinical description of children who share features of a non-progressive brain injury or lesion acquired during the antenatal, perinatal or early postnatal period. The clinical manifestations of cerebral palsy vary greatly in the type of movement disorder, the degree of functional ability and limitation and the affected parts of the body. There is currently no cure, but progress is being made in both the prevention and the amelioration of the brain injury. For example, administration of magnesium sulfate during premature labour and cooling of high-risk infants can reduce the rate and severity of cerebral palsy. Although the disorder affects individuals throughout their lifetime, most cerebral palsy research efforts and management strategies currently focus on the needs of children. Clinical management of children with cerebral palsy is directed towards maximizing function and participation in activities and minimizing the effects of the factors that can make the condition worse, such as epilepsy, feeding challenges, hip dislocation and scoliosis. These management strategies include enhancing neurological function during early development; managing medical co-morbidities, weakness and hypertonia; using rehabilitation technologies to enhance motor function; and preventing secondary musculoskeletal problems. Meeting the needs of people with cerebral palsy in resource-poor settings is particularly challenging. C1 [Graham, H. Kerr] Royal Childrens Hosp, Dept Orthopaed, 50 Flemington Rd, Parkville, Vic 3052, Australia. [Graham, H. Kerr] Royal Childrens Hosp, Murdoch Childrens Res Inst, Parkville, Vic, Australia. [Graham, H. Kerr] Univ Melbourne, Royal Childrens Hosp, Dept Paediat, Melbourne, Vic 3010, Australia. [Rosenbaum, Peter] McMaster Univ, CanChild Ctr, Hamilton, ON, Canada. [Paneth, Nigel] Michigan State Univ, Coll Human Med, Dept Epidemiol, E Lansing, MI 48824 USA. [Paneth, Nigel] Michigan State Univ, Coll Human Med, Dept Biostat, E Lansing, MI 48824 USA. [Paneth, Nigel] Michigan State Univ, Coll Human Med, Dept Pediat & Human Dev, E Lansing, MI 48824 USA. [Dan, Bernard] Univ Libre Bruxelles, Dept Neurol, Brussels, Belgium. [Lin, Jean-Pierre] Evelina Childrens Hosp, Complex Motor Disorders Serv, London, England. [Damiano, Diane L.] NIH, Dept Rehabil Med, Bethesda, MD 20892 USA. [Becher, Jules G.] Vrije Univ Amsterdam, Med Ctr, Dept Rehabil Med, Amsterdam, Netherlands. [Gaebler-Spira, Deborah] Rehabil Inst Chicago, Feinberg Northwestern Sch Med, Dept Phys Med & Rehabil & Pediat, Chicago, IL 60611 USA. [Colver, Allan] Newcastle Univ, Inst Hlth & Soc, Newcastle Upon Tyne, Tyne & Wear, England. [Reddihough, DinahS.; Crompton, Kylie E.] Royal Childrens Hosp, Murdoch Childrens Res Inst, Dev Disabil & Rehabil Res, Parkville, Vic, Australia. [Lieber, Richard L.] Rehabil Inst Chicago, Chicago, IL 60611 USA. RP Graham, HK (reprint author), Royal Childrens Hosp, Dept Orthopaed, 50 Flemington Rd, Parkville, Vic 3052, Australia. EM kerr.graham@rch.org.au OI Dan, Bernard/0000-0002-2051-9876 FU Allergan; Hugh Williamson Foundation; National Health and Medical Research Council of Australia, Cerebral Palsy Centre of Research Excellence (CRE); Guy's and St. Thomas Charity New Services and Innovation Grant [G060708]; Dystonia Society UK [01/2011, 07/2013]; Action Medical Research [GN2097]; Medtronic Ltd. FX H.K.G. has received unrestricted educational grants from pharmaceutical companies including Allergan. Current research support is from the Hugh Williamson Foundation and the National Health and Medical Research Council of Australia, Cerebral Palsy Centre of Research Excellence (CRE). J.-P.L. has held grants from the Guy's and St. Thomas Charity New Services and Innovation Grant G060708; the Dystonia Society UK Grants 01/2011 and 07/2013 and Action Medical Research GN2097, has acted as a consultant for Medtronic Ltd and benefited from unrestricted educational grants by Medtronic Ltd. B.D. and P.R. are senior members of the editorial board of Mac Keith Press, the publisher of the 2014 book "Cerebral Palsy: Science and Clinical Practice" (Mac Keith Press: London) and have contributed to several chapters, for which they are likely to receive modest royalties. All other authors declare no competing interests. NR 282 TC 9 Z9 9 U1 17 U2 17 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 2056-676X J9 NAT REV DIS PRIMERS JI Nat. Rev. Dis. Primers PD JAN 7 PY 2016 VL 2 AR 15082 DI 10.1038/nrdp.2015.82 PG 24 WC Medicine, General & Internal SC General & Internal Medicine GA DT3CL UT WOS:000381358000001 PM 27188686 ER PT J AU Krishnakumar, R Chen, AF Pantovich, MG Danial, M Parchem, RJ Labosky, PA Blelloch, R AF Krishnakumar, Raga Chen, Amy F. Pantovich, Marisol G. Danial, Muhammad Parchem, Ronald J. Labosky, Patricia A. Blelloch, Robert TI FOXD3 Regulates Pluripotent Stem Cell Potential by Simultaneously Initiating and Repressing Enhancer Activity SO CELL STEM CELL LA English DT Article ID CHROMATIN REMODELING COMPLEX; TISSUE-SPECIFIC ENHANCERS; FORKHEAD BOX PROTEINS; EARLY MOUSE EMBRYO; NEURAL CREST; TRANSCRIPTION FACTORS; PRIMED PLURIPOTENCY; UP-REGULATION; SELF-RENEWAL; ES CELLS AB Early development is governed by the ability of pluripotent cells to retain the full range of developmental potential and respond accurately to developmental cues. This property is achieved in large part by the temporal and contextual regulation of gene expression by enhancers. Here, we evaluated regulation of enhancer activity during differentiation of embryonic stem to epiblast cells and uncovered the forkhead transcription factor FOXD3 as a major regulator of the developmental potential of both pluripotent states. FOXD3 bound to distinct sites in the two cell types priming enhancers through a dual-functional mechanism. It recruited the SWI/SNF chromatin remodeling complex ATPase BRG1 to promote nucleosome removal while concurrently inhibiting maximal activation of the same enhancers by recruiting histone deacetylases1/2. Thus, FOXD3 prepares cognate genes for future maximal expression by establishing and simultaneously repressing enhancer activity. Through switching of target sites, FOXD3 modulates the developmental potential of pluripotent cells as they differentiate. C1 [Krishnakumar, Raga; Chen, Amy F.; Parchem, Ronald J.; Blelloch, Robert] Univ Calif San Francisco, Ctr Reprod Sci, Eli & Edythe Broad Ctr Regenerat Med & Stem Cell, San Francisco, CA 94143 USA. [Krishnakumar, Raga; Chen, Amy F.; Pantovich, Marisol G.; Danial, Muhammad; Parchem, Ronald J.; Blelloch, Robert] Univ Calif San Francisco, Dept Urol, San Francisco, CA 94143 USA. [Labosky, Patricia A.] NIH, Off Strateg Coordinat, Div Program Coordinat Planning & Strateg Initiat, Bethesda, MD 20892 USA. [Labosky, Patricia A.] NIH, Off Director, Bethesda, MD 20892 USA. RP Blelloch, R (reprint author), Univ Calif San Francisco, Ctr Reprod Sci, Eli & Edythe Broad Ctr Regenerat Med & Stem Cell, San Francisco, CA 94143 USA.; Blelloch, R (reprint author), Univ Calif San Francisco, Dept Urol, San Francisco, CA 94143 USA. EM blellochr@stemcell.ucsf.edu FU NIH [R01 GM101180, U54 HD055764]; CIRM [RN2-00906-1]; AP Gianinni Postdoctoral Award FX We thank Jennifer Plank and Scott Oakes for technical advice and Glencijoy David, Brandon Chu, Greg Bronevetsky, and Richard Lao for technical support. We acknowledge Indiana University for access to their Mason cluster of computers. We thank the following people for critical reading of the manuscript: Marco Conti, Diana Laird, Barbara Panning, Brian DeVeale, Jacob Freimer, Jennifer Plank, Archana Shenoy, Mayya Shveygert, John Vincent, and Julia Ye. This project was funded by NIH (R01 GM101180, U54 HD055764) and CIRM (RN2-00906-1) to R.B. and an AP Gianinni Postdoctoral Award to R.K. NR 68 TC 3 Z9 3 U1 4 U2 5 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 1934-5909 EI 1875-9777 J9 CELL STEM CELL JI Cell Stem Cell PD JAN 7 PY 2016 VL 18 IS 1 BP 104 EP 117 DI 10.1016/j.stem.2015.10.003 PG 14 WC Cell & Tissue Engineering; Cell Biology SC Cell Biology GA DG8GP UT WOS:000372321300016 PM 26748757 ER PT J AU Rao, VK AF Rao, V. Koneti TI Serendipity in splendid isolation: rapamycin SO BLOOD LA English DT Editorial Material ID SIROLIMUS; MECHANISM C1 [Rao, V. Koneti] NIH, Bethesda, MD 20892 USA. RP Rao, VK (reprint author), NIH, Bethesda, MD 20892 USA. NR 10 TC 1 Z9 1 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 2021 L ST NW, SUITE 900, WASHINGTON, DC 20036 USA SN 0006-4971 EI 1528-0020 J9 BLOOD JI Blood PD JAN 7 PY 2016 VL 127 IS 1 BP 5 EP 6 DI 10.1182/blood-2015-11-679829 PG 2 WC Hematology SC Hematology GA DC5SS UT WOS:000369281300003 PM 26744433 ER PT J AU Palmer, J Chai, XY Pidala, J Inamoto, Y Martin, PJ Storer, B Pusic, I Flowers, MED Arora, M Pavletic, SZ Lee, SJ AF Palmer, Jeanne Chai, Xiaoyu Pidala, Joseph Inamoto, Yoshihiro Martin, Paul J. Storer, Barry Pusic, Iskra Flowers, Mary E. D. Arora, Mukta Pavletic, Steven Z. Lee, Stephanie J. TI Predictors of survival, nonrelapse mortality, and failure-free survival in patients treated for chronic graft-versus-host disease SO BLOOD LA English DT Article ID CONSENSUS DEVELOPMENT PROJECT; WORKING GROUP-REPORT; MEASURING THERAPEUTIC RESPONSE; CHRONIC GVHD CONSORTIUM; LONG-TERM SURVIVAL; CLINICAL-TRIALS; CELL TRANSPLANTATION; SYSTEMIC TREATMENT; LATE DEATHS; CRITERIA AB Chronic graft-versus-host disease (GVHD) is a pleotropic syndrome that lacks validated methods of measuring response in clinical trials, although several end points have been proposed. To investigate the prognostic significance of these proposed end points, such as the 2005 National Institutes of Health (NIH) response measures, 2014 NIH response measures, clinician-reported response, and patient-reported response, we tested their ability to predict subsequent overall survival (OS), nonrelapse mortality (NRM), and failure-free survival (FFS). Patients (n = 575) were enrolled on a prospective chronic GVHD observational trial. At 6 months, clinician-reported response (P = .004) and 2014 NIH-calculated response (P = .001) correlated with subsequent FFS, and clinician reported response predicted OS (P = .007). Multivariate models were used to identify changes in organ involvement, laboratory values, and patient-reported outcomes that were associated with long-term outcomes. At 6 months, a change in the 2005 NIH 0 to 3 clinician-reported skin score and 0 to 10 patient-reported itching score predicted subsequent FFS. Change in the Lee skin symptom score and Functional Assessment of Cancer Therapy-Bone Marrow Transplant score predicted subsequent OS. Change in the Lee skin symptom score predicted subsequent NRM. This study provides evidence that clinician-reported response and patient-reported outcomes are predictive of long-term survival. C1 [Palmer, Jeanne] Mayo Clin, Div Hematol Oncol, Phoenix, AZ 85054 USA. [Chai, Xiaoyu; Inamoto, Yoshihiro; Martin, Paul J.; Storer, Barry; Flowers, Mary E. D.; Lee, Stephanie J.] Fred Hutchinson Canc Res Ctr, Div Clin Res, 1124 Columbia St, Seattle, WA 98104 USA. [Pidala, Joseph] Univ S Florida, H Lee Moffitt Canc Ctr, Blood & Marrow Transplantat, Tampa, FL 33682 USA. [Inamoto, Yoshihiro] Natl Canc Ctr, Div Hematopoiet Stem Cell Transplantat, 1-1 Tsukiji 5 chome, Tokyo, Japan. [Pusic, Iskra] Washington Univ, Div Hematol Oncol, St Louis, MO USA. [Arora, Mukta] Univ Minnesota, Blood & Marrow Transplant Program, Minneapolis, MN USA. [Pavletic, Steven Z.] NCI, NIH, Bethesda, MD 20892 USA. RP Palmer, J (reprint author), Mayo Clin Phoenix, 5777 East Mayo Blvd, Phoenix, AZ 85054 USA. EM palmer.jeanne@mayo.edu FU NCI NIH HHS [CA118953, R01 CA118953, U01 CA118953, U54 CA163438] NR 42 TC 2 Z9 2 U1 1 U2 1 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 2021 L ST NW, SUITE 900, WASHINGTON, DC 20036 USA SN 0006-4971 EI 1528-0020 J9 BLOOD JI Blood PD JAN 7 PY 2016 VL 127 IS 1 BP 160 EP 166 DI 10.1182/blood-2015-08-662874 PG 7 WC Hematology SC Hematology GA DC5SS UT WOS:000369281300025 PM 26527676 ER PT J AU Conomos, MP Laurie, CA Stilp, AM Gogarten, SM McHugh, CP Nelson, SC Sofer, T Fernandez-Rhodes, L Justice, AE Graff, M Young, KL Seyerle, AA Avery, CL Taylor, KD Rotter, JI Talavera, GA Daviglus, ML Wassertheil-Smoller, S Schneiderman, N Heiss, G Kaplan, RC Franceschini, N Reiner, AP Shaffer, JR Barr, RG Kerr, KF Browning, SR Browning, BL Weir, BS Aviles-Santa, ML Papanicolaou, GJ Lumley, T Szpiro, AA North, KE Rice, K Thornton, TA Laurie, CC AF Conomos, Matthew P. Laurie, Cecelia A. Stilp, Adrienne M. Gogarten, Stephanie M. McHugh, Caitlin P. Nelson, Sarah C. Sofer, Tamar Fernandez-Rhodes, Lindsay Justice, Anne E. Graff, Mariaelisa Young, Kristin L. Seyerle, Amanda A. Avery, Christy L. Taylor, Kent D. Rotter, Jerome I. Talavera, Gregory A. Daviglus, Martha L. Wassertheil-Smoller, Sylvia Schneiderman, Neil Heiss, Gerardo Kaplan, Robert C. Franceschini, Nora Reiner, Alex P. Shaffer, John R. Barr, R. Graham Kerr, Kathleen F. Browning, Sharon R. Browning, Brian L. Weir, Bruce S. Aviles-Santa, M. Larissa Papanicolaou, George J. Lumley, Thomas Szpiro, Adam A. North, Kari E. Rice, Ken Thornton, Timothy A. Laurie, Cathy C. TI Genetic Diversity and Association Studies in US Hispanic/Latino Populations: Applications in the Hispanic Community Health Study/Study of Latinos SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Article ID GENOME-WIDE ASSOCIATION; LINEAR MIXED MODELS; ADMIXED POPULATIONS; UNITED-STATES; MEXICAN-AMERICANS; ENVIRONMENT DATA; QUALITY-CONTROL; STRATIFICATION; ANCESTRY; TRAITS AB US Hispanic/Latino individuals are diverse in genetic ancestry, culture, and environmental exposures. Here, we characterized and controlled for this diversity in genome-wide association studies (GWASs) for the Hispanic Community Health Study/Study of Latinos (HCHS/SOL). We simultaneously estimated population-structure principal components (PCs) robust to familial relatedness and pairwise kinship coefficients (KCs) robust to population structure, admixture, and Hardy-Weinberg departures. The PCs revealed substantial genetic differentiation within and among six self-identified background groups (Cuban, Dominican, Puerto Rican, Mexican, and Central and South American). To control for variation among groups, we developed a multi-dimensional clustering method to define a "genetic-analysis group" variable that retains many properties of self-identified background while achieving substantially greater genetic homogeneity within groups and including participants with non-specific self-identification. In GWASs of 22 biomedical traits, we used a linear mixed model (LMM) including pairwise empirical KCs to account for familial relatedness, PCs for ancestry, and genetic-analysis groups for additional group-associated effects. Including the genetic-analysis group as a covariate accounted for significant trait variation in 8 of 22 traits, even after we fit 20 PCs. Additionally, genetic-analysis groups had significant heterogeneity of residual variance for 20 of 22 traits, and modeling this heteroscedasticity within the LMM reduced genomic inflation for 19 traits. Furthermore, fitting an LMM that utilized a genetic-analysis group rather than a self-identified background group achieved higher power to detect previously reported associations. We expect that the methods applied here will be useful in other studies with multiple ethnic groups, admixture, and relatedness. C1 [Conomos, Matthew P.; Laurie, Cecelia A.; Stilp, Adrienne M.; Gogarten, Stephanie M.; McHugh, Caitlin P.; Nelson, Sarah C.; Sofer, Tamar; Kerr, Kathleen F.; Browning, Sharon R.; Weir, Bruce S.; Szpiro, Adam A.; Rice, Ken; Thornton, Timothy A.; Laurie, Cathy C.] Univ Washington, Dept Biostat, Seattle, WA 98195 USA. [Fernandez-Rhodes, Lindsay; Justice, Anne E.; Graff, Mariaelisa; Young, Kristin L.; Seyerle, Amanda A.; Avery, Christy L.; Heiss, Gerardo; Franceschini, Nora; North, Kari E.] Univ N Carolina, Dept Epidemiol, Chapel Hill, NC 27514 USA. [Taylor, Kent D.; Rotter, Jerome I.] Harbor UCLA Med Ctr, Inst Translat Genom & Populat Sci, Los Angeles Biomed Res Inst, Torrance, CA 90502 USA. [Taylor, Kent D.; Rotter, Jerome I.] Harbor UCLA Med Ctr, Dept Pediat, Torrance, CA 90502 USA. [Talavera, Gregory A.] San Diego State Univ, Grad Sch Publ Hlth, San Diego, CA 92182 USA. [Daviglus, Martha L.] Univ Illinois, Inst Minor Hlth, Chicago, IL 60612 USA. [Wassertheil-Smoller, Sylvia; Kaplan, Robert C.] Albert Einstein Coll Med, Dept Epidemiol & Populat Hlth, Bronx, NY 10461 USA. [Schneiderman, Neil] Univ Miami, Dept Psychol & Behav Med, Miami, FL 33124 USA. [Reiner, Alex P.] Univ Washington, Dept Epidemiol, Seattle, WA 98195 USA. [Shaffer, John R.] Univ Pittsburgh, Grad Sch Publ Hlth, Dept Human Genet, Pittsburgh, PA 15261 USA. [Barr, R. Graham] Columbia Univ, Med Ctr, Dept Med, New York, NY 10032 USA. [Barr, R. Graham] Columbia Univ, Med Ctr, Dept Epidemiol, New York, NY 10032 USA. [Browning, Brian L.] Univ Washington, Dept Med, Seattle, WA 98077 USA. [Aviles-Santa, M. Larissa; Papanicolaou, George J.] NHLBI, Div Cardiovasc Sci, NIH, Bethesda, MD 20892 USA. [Lumley, Thomas] Univ Auckland, Dept Stat, Auckland 1010, New Zealand. RP Conomos, MP (reprint author), Univ Washington, Dept Biostat, Seattle, WA 98195 USA. EM mconomos@uw.edu; cclaurie@uw.edu RI Browning, Sharon/B-1530-2008; Browning, Brian/A-1178-2010; Kerr, Kathleen/A-2893-2013; OI Browning, Sharon/0000-0001-7251-9715; Browning, Brian/0000-0001-6454-6633; Nelson, Sarah/0000-0002-2109-6465; Gogarten, Stephanie/0000-0002-7231-9745; Seyerle, Amanda/0000-0001-5660-3837; Sofer, Tamar/0000-0001-8520-8860 FU NHLBI [N01-HC65233]; University of Miami [N01-HC65234]; Albert Einstein College of Medicine [N01-HC65235]; Northwestern University [N01-HC65236]; San Diego State University [N01-HC65237]; NHLBI; NIDCR [HHSN268201300005C AM03, MOD03]; NIH Department of Health and Human Services [HSN26220/20054C]; National Center for Advancing Translational Science Clinical Translational Science Institute [UL1TR000124]; NIDDK Diabetes Research Center [DK063491]; [1R01DK101855-01]; [13GRNT16490017] FX We thank the participants and staff of the Hispanic Community Health Study/Study of Latinos (HCHS/SOL) for their contributions to this study. The baseline examination of HCHS/SOL was carried out as a collaborative study supported by contracts from the NHLBI to the University of North Carolina (N01-HC65233), University of Miami (N01-HC65234), Albert Einstein College of Medicine (N01-HC65235), Northwestern University (N01-HC65236), and San Diego State University (N01-HC65237). The following institutes, centers, and offices contributed to the first phase of HCHS/SOL through a transfer of funds to the NHLBI: National Institute on Minority Health and Health Disparities, National Institute on Deafness and Other Communication Disorders, National Institute of Dental and Craniofacial Research (NIDCR), National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK), National Institute of Neurological Disorders and Stroke, and NIH Office of Dietary Supplements. The Genetic Analysis Center at the University of Washington was supported by NHLBI and NIDCR contracts (HHSN268201300005C AM03 and MOD03). Additional analysis support was provided by 1R01DK101855-01 and 13GRNT16490017. Genotyping efforts were supported by the NIH Department of Health and Human Services (HSN26220/20054C), National Center for Advancing Translational Science Clinical Translational Science Institute (UL1TR000124), and NIDDK Diabetes Research Center (DK063491). This manuscript has been reviewed by the HCHS/SOL Publications Committee for scientific content and consistency of data interpretation with previous HCHS/SOL publications. NR 79 TC 16 Z9 16 U1 4 U2 12 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 0002-9297 EI 1537-6605 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD JAN 7 PY 2016 VL 98 IS 1 BP 165 EP 184 DI 10.1016/j.ajhg.2015.12.001 PG 20 WC Genetics & Heredity SC Genetics & Heredity GA DA8JL UT WOS:000368050800012 PM 26748518 ER PT J AU Shah, SS Rockett, KA Jallow, M Sisay-Joof, F Bojang, KA Pinder, M Jeffreys, A Craik, R Hubbart, C Wellems, TE Kwiatkowski, DP AF Shah, Shivang S. Rockett, Kirk A. Jallow, Muminatou Sisay-Joof, Fatou Bojang, Kalifa A. Pinder, Margaret Jeffreys, Anna Craik, Rachel Hubbart, Christina Wellems, Thomas E. Kwiatkowski, Dominic P. CA MalariaGEN Consortium TI Heterogeneous alleles comprising G6PD deficiency trait in West Africa exert contrasting effects on two major clinical presentations of severe malaria SO MALARIA JOURNAL LA English DT Article DE G6PD deficiency; malaria ID SICKLE-CELL TRAIT; PLASMODIUM-FALCIPARUM MALARIA; GLUCOSE-6-PHOSPHATE-DEHYDROGENASE DEFICIENCY; X-CHROMOSOME; HUMAN GENOME; RESISTANCE; DEHYDROGENASE; ASSOCIATION; PROTECTION; ERYTHROCYTES AB Background: Glucose-6-phosphate dehydrogenase (G6PD) deficiency exhibits considerable allelic heterogeneity which manifests with variable biochemical and clinical penetrance. It has long been thought that G6PD deficiency confers partial protection against severe malaria, however prior genetic association studies have disagreed with regard to the strength and specificity of a protective effect, which might reflect differences in the host genetic background, environmental influences, or in the specific clinical phenotypes considered. Methods: A case-control association study of severe malaria was conducted in The Gambia, a region in West Africa where there is considerable allelic heterogeneity underlying expression of G6PD deficiency trait, evaluating the three major nonsynonymous polymorphisms known to be associated with enzyme deficiency (A968G, T542A, and C202T) in a cohort of 3836 controls and 2379 severe malaria cases. Results: Each deficiency allele exhibited a similar trend toward protection against severe malaria overall (15-26 % reduced risk); however, in stratifying severe malaria to two of its constituent clinical subphenotypes, severe malarial anaemia (SMA) and cerebral malaria (CM), the three deficiency alleles exhibited trends of opposing effect, with risk conferred to SMA and protection with respect to CM. To assess the overall effect of G6PD deficiency trait, deficiency alleles found across all three loci were pooled. G6PD deficiency trait was found to be significantly associated with protection from severe malaria overall (OR 0.83 [0.75-0.92], P = 0.0006), but this was limited to CM (OR 0.73 [0.61-0.87], P = 0.0005), with a trend toward increased risk for SMA, especially in fully-deficient individuals (OR 1.43 [0.99-2.08], P = 0.056). Sex-stratified testing largely comported with these results, with evidence suggesting that protection by G6PD deficiency trait is conferred to both males and females, though susceptibility to SMA may be restricted to fully-deficient male hemizygotes. Conclusions: In a part of Africa where multiple alleles contribute to expression of G6PD deficiency trait, these findings clarify and extend previous work done in populations where a single variant predominates, and taken together suggest a causal role for G6PD deficiency trait itself with respect to severe malaria, with opposing effects seen on two major clinical subphenotypes. C1 [Shah, Shivang S.; Rockett, Kirk A.; Jeffreys, Anna; Craik, Rachel; Hubbart, Christina; Kwiatkowski, Dominic P.] Univ Oxford, Wellcome Trust Ctr Human Genet, Oxford, England. [Jallow, Muminatou; Sisay-Joof, Fatou; Bojang, Kalifa A.; Pinder, Margaret] MRC Labs, Banjul, Fajara, Gambia. [Kwiatkowski, Dominic P.] Wellcome Trust Sanger Inst, Hinxton, England. [Shah, Shivang S.; Wellems, Thomas E.] NIAID, Lab Malaria & Vector Res, NIH, Bethesda, MD 20892 USA. RP Shah, SS (reprint author), Univ Oxford, Wellcome Trust Ctr Human Genet, Oxford, England. EM ssshah03@gmail.com OI Kwiatkowski, Dominic/0000-0002-5023-0176 FU Wellcome Trust [077383/Z/05/Z, 090770/Z/09/Z, 075491/Z/04, 090532/Z/09/Z]; Foundation for the National Institutes of Health as part of the Bill and Melinda Gates Grand Challenges in Global Health Initiative [566]; Medical Research Council [G0600718, G19/9]; Wellcome Trust Sanger Institute [077012/Z/05/Z]; Intramural Research Program of the National Institute of Allergy and Infectious Diseases at the National Institutes of Health; Medical Scientist Training Program at the NIH FX We thank the all participants and communities in The Gambia who made this study possible and the healthcare workers who assisted with this work. MalariaGEN is supported by the Wellcome Trust (077383/Z/05/Z) and by the Foundation for the National Institutes of Health (566) as part of the Bill and Melinda Gates Grand Challenges in Global Health Initiative. The Resource Centre for Genomic Epidemiology of Malaria is supported by the Wellcome Trust (090770/Z/09/Z). Support was also provided by the Medical Research Council (G0600718). Dominic Kwiatkowski receives support from the Medical Research Council (G19/9). The Wellcome Trust also provides core awards to The Wellcome Trust Centre for Human Genetics (075491/Z/04; 090532/Z/09/Z) and the Wellcome Trust Sanger Institute (077012/Z/05/Z). This study was also supported by the Intramural Research Program of the National Institute of Allergy and Infectious Diseases at the National Institutes of Health, and Shivang Shah is also supported by the Medical Scientist Training Program at the NIH. NR 54 TC 4 Z9 4 U1 0 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 JAN 7 PY 2016 VL 15 DI 10.1186/s12936-015-1045-0 PG 8 WC Infectious Diseases; Parasitology; Tropical Medicine SC Infectious Diseases; Parasitology; Tropical Medicine GA DA8MQ UT WOS:000368059400001 PM 26738565 ER PT J AU Shi, M Deroo, LA Sandler, DP Weinberg, CR AF Shi, Min Deroo, Lisa A. Sandler, Dale P. Weinberg, Clarice R. TI Migraine and possible etiologic heterogeneity for hormone-receptor-negative breast cancer (vol 5, 14943, 2016) SO SCIENTIFIC REPORTS LA English DT Correction C1 [Sandler, Dale P.] NIEHS, Epidemiol Branch, NIH, DHHS, Res Triangle Pk, NC 27709 USA. NR 1 TC 0 Z9 0 U1 1 U2 2 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 JAN 7 PY 2016 VL 6 AR 17238 DI 10.1038/srep17238 PG 1 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA DA9ZG UT WOS:000368167700001 PM 26740285 ER PT J AU Wang, NY Hoffman, EP Chen, LL Chen, L Zhang, Z Liu, CY Yu, GQ Herrington, DM Clarke, R Wang, Y AF Wang, Niya Hoffman, Eric P. Chen, Lulu Chen, Li Zhang, Zhen Liu, Chunyu Yu, Guoqiang Herrington, David M. Clarke, Robert Wang, Yue TI Mathematical modelling of transcriptional heterogeneity identifies novel markers and subpopulations in complex tissues SO SCIENTIFIC REPORTS LA English DT Article ID CYCLE-REGULATED GENES; CELL-CYCLE; EXPRESSION DECONVOLUTION; SEPARATION; PATTERNS; CANCER; BRAIN; TOOL AB Tissue heterogeneity is both a major confounding factor and an underexploited information source. While a handful of reports have demonstrated the potential of supervised computational methods to deconvolute tissue heterogeneity, these approaches require a priori information on the marker genes or composition of known subpopulations. To address the critical problem of the absence of validated marker genes for many (including novel) subpopulations, we describe convex analysis of mixtures (CAM), a fully unsupervised in silico method, for identifying subpopulation marker genes directly from the original mixed gene expressions in scatter space that can improve molecular analyses in many biological contexts. Validated with predesigned mixtures, CAM on the gene expression data from peripheral leukocytes, brain tissue, and yeast cell cycle, revealed novel marker genes that were otherwise undetectable using existing methods. Importantly, CAM requires no a priori information on the number, identity, or composition of the subpopulations present in mixed samples, and does not require the presence of pure subpopulations in sample space. This advantage is significant in that CAM can achieve all of its goals using only a small number of heterogeneous samples, and is more powerful to distinguish between phenotypically similar subpopulations. C1 [Wang, Niya; Chen, Lulu; Yu, Guoqiang; Wang, Yue] Virginia Polytech Inst & State Univ, Dept Elect & Comp Engn, Arlington, VA 22203 USA. [Hoffman, Eric P.] Childrens Natl Med Ctr, Med Genet Res Ctr, Washington, DC 20007 USA. [Chen, Li] NIH, Pediat Oncol Branch, Gaithersburg, MD 20877 USA. [Zhang, Zhen] Johns Hopkins Univ, Dept Pathol, Baltimore, MD 21231 USA. [Liu, Chunyu] Univ Illinois, Dept Psychiat, Chicago, IL 60607 USA. [Herrington, David M.] Wake Forest Univ, Dept Med, Winston Salem, NC 27157 USA. [Clarke, Robert] Georgetown Univ, Lombardi Comprehens Canc Ctr, Washington, DC 20057 USA. RP Wang, Y (reprint author), Virginia Polytech Inst & State Univ, Dept Elect & Comp Engn, Arlington, VA 22203 USA. EM yuewang@vt.edu RI Clarke, Robert/A-6485-2008 OI Clarke, Robert/0000-0002-9278-0854 FU National Institutes of Health [NS029525, CA160036, CA184902, ES024988, CA149653, HL111362] FX This work was funded in part by the National Institutes of Health under Grants NS029525, CA160036, CA184902, ES024988, CA149653, and HL111362. NR 37 TC 2 Z9 2 U1 3 U2 8 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 2045-2322 J9 SCI REP-UK JI Sci Rep PD JAN 7 PY 2016 VL 6 AR 18909 DI 10.1038/srep18909 PG 12 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA DB0IQ UT WOS:000368192200001 PM 26739359 ER PT J AU Shen, YJ Chalopin, D Garcia, T Boswell, M Boswell, W Shiryev, SA Agarwala, R Volff, JN Postlethwait, JH Schartl, M Minx, P Warren, WC Walter, RB AF Shen, Yingjia Chalopin, Domitille Garcia, Tzintzuni Boswell, Mikki Boswell, William Shiryev, Sergey A. Agarwala, Richa Volff, Jean-Nicolas Postlethwait, John H. Schartl, Manfred Minx, Patrick Warren, Wesley C. Walter, Ronald B. TI X. couchianus and X. hellerii genome models provide genomic variation insight among Xiphophorus species SO BMC GENOMICS LA English DT Article DE Xiphophorus; X. couchianus; X. hellerii; Genome assembly; Annotation; Single nucleotide change; Genome comparison; NGS ID FISH; IDENTIFICATION; TRANSCRIPTOME; EXPRESSION; RESOURCES; MACULATUS; EVOLUTION; DISCOVERY; PLATYFISH; MEXICO AB Background: Xiphophorus fishes are represented by 26 live-bearing species of tropical fish that express many attributes (e.g., viviparity, genetic and phenotypic variation, ecological adaptation, varied sexual developmental mechanisms, ability to produce fertile interspecies hybrids) that have made attractive research models for over 85 years. Use of various interspecies hybrids to investigate the genetics underlying spontaneous and induced tumorigenesis has resulted in the development and maintenance of pedigreed Xiphophorus lines specifically bred for research. The recent availability of the X. maculatus reference genome assembly now provides unprecedented opportunities for novel and exciting comparative research studies among Xiphophorus species. Results: We present sequencing, assembly and annotation of two new genomes representing Xiphophorus couchianus and Xiphophorus hellerii. The final X. couchianus and X. hellerii assemblies have total sizes of 708 Mb and 734 Mb and correspond to 98 % and 102 % of the X. maculatus Jp 163 A genome size, respectively. The rates of single nucleotide change range from 1 per 52 bp to 1 per 69 bp among the three genomes and the impact of putatively damaging variants are presented. In addition, a survey of transposable elements allowed us to deduce an ancestral TE landscape, uncovered potential active TEs and document a recent burst of TEs during evolution of this genus. Conclusions: Two new Xiphophorus genomes and their corresponding transcriptomes were efficiently assembled, the former using a novel guided assembly approach. Three assembled genome sequences within this single vertebrate order of new world live-bearing fishes will accelerate our understanding of relationship between environmental adaptation and genome evolution. In addition, these genome resources provide capability to determine allele specific gene regulation among interspecies hybrids produced by crossing any of the three species that are known to produce progeny predisposed to tumor development. C1 [Shen, Yingjia; Garcia, Tzintzuni; Boswell, Mikki; Boswell, William; Walter, Ronald B.] Texas State Univ, Dept Chem & Biochem, Xiphophorus Genet Stock Ctr, San Marcos, TX 78666 USA. [Shen, Yingjia] Minist Educ, Key Lab Coastal & Wetland Ecosyst, Xiamen 361102, Fujian, Peoples R China. [Chalopin, Domitille; Volff, Jean-Nicolas] Univ Lyon 1, Ctr Natl Rech Sci, Ecole Normale Super Lyon, Inst Genom Fonct Lyon,Unite Mixte Rech 5242, F-69365 Lyon, France. [Shiryev, Sergey A.; Agarwala, Richa] Natl Lib Med, Natl Ctr Biotechnol Informat, Bethesda, MD 20894 USA. [Postlethwait, John H.] Univ Oregon, Inst Neurosci, Eugene, OR 97403 USA. [Schartl, Manfred] Univ Wurzburg, Biozentrum, Physiol Chem 1, D-97074 Wurzburg, Germany. [Schartl, Manfred] Univ Clin Wurzburg, Comprehens Canc Ctr Mainfranken, D-97074 Wurzburg, Germany. [Minx, Patrick; Warren, Wesley C.] Washington Univ, Sch Med, Genome Sequencing Ctr, St Louis, MO 63108 USA. RP Walter, RB (reprint author), Texas State Univ, Dept Chem & Biochem, Xiphophorus Genet Stock Ctr, 419 Centennial Hall,601 Univ Dr, San Marcos, TX 78666 USA. EM RWalter@txstate.edu OI Schartl, Manfred/0000-0001-9882-5948 FU National Institutes of Health, Division of Comparative Medicine [R24 OD-011120, R24 OD-011198, R24 OD-011199, R24 OD-018555]; Natural Science Foundation of Fujian Province of China [2015J05074] FX We thank the Xiphophorus Genetic Stock Center, Texas State University, for maintaining the pedigreed fish lines, helping with dissections, and caring for the animals used in this study. This work was supported by the National Institutes of Health, Division of Comparative Medicine, R24 OD-011120 and R24 OD-011198, R24 OD-011199, R24 OD-018555 and Natural Science Foundation of Fujian Province of China (No. 2015J05074). NR 31 TC 0 Z9 0 U1 10 U2 17 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 JAN 7 PY 2016 VL 17 AR 37 DI 10.1186/s12864-015-2361-z PG 13 WC Biotechnology & Applied Microbiology; Genetics & Heredity SC Biotechnology & Applied Microbiology; Genetics & Heredity GA DA3JH UT WOS:000367692500004 PM 26742787 ER PT J AU Messina, I Cattaneo, L Venuti, P de Pisapia, N Serra, M Esposito, G Rigo, P Farneti, A Bornstein, MH AF Messina, Irene Cattaneo, Luigi Venuti, Paola de Pisapia, Nicola Serra, Mauro Esposito, Gianluca Rigo, Paola Farneti, Alessandra Bornstein, Marc H. TI Sex-Specific Automatic Responses to Infant Cries: TMS Reveals Greater Excitability in Females than Males in Motor Evoked Potentials SO FRONTIERS IN PSYCHOLOGY LA English DT Article DE parenting; baby cries; MEPS; TMS; sex differences ID TRANSCRANIAL MAGNETIC STIMULATION; MIRROR-NEURON SYSTEM; MATERNAL SENSITIVITY; AMYGDALA RESPONSE; BRAIN RESPONSES; DISTRESS VOCALIZATIONS; PARENTING EXPERIENCES; EMOTIONAL-REACTIONS; TYPICAL DEVELOPMENT; TRACT EXCITABILITY AB Neuroimaging reveals that infant cries activate parts of the premotor cortical system. To validate this effect in a more direct way, we used event related transcranial magnetic stimulation (TMS). Here, we investigated the presence and the time course of modulation of motor cortex excitability in young adults who listened to infant cries. Specifically, we recorded motor evoked potentials (MEPs) from the biceps brachii (BB) and interosseus dorsalis prirnus (ID1) muscles as produced by TMS delivered from 0 to 250 ms after sound onset in six steps of 50 ms in 10 females and 10 males. We observed an excitatory modulation of MEPs at 100 ms from the onset of infant cry specific to females and to the IDl muscle. We regard this modulation as a response to natural cry sounds because it was attenuated to stimuli increasingly different from natural cry and absent in a separate group of females who listened to non-cry stimuli physically matched to natural infant cries. Furthermore, the 100 ms latency of this response is not compatible with a voluntary reaction to the stimulus but suggests an automatic, bottom-up audiomotor association. The brains of adult females appear to be tuned to respond to infant cries with automatic motor excitation. C1 [Messina, Irene] Univ Padua, Dept Philosophy Sociol Educ & Appl Psychol, Padua, Italy. [Cattaneo, Luigi] Univ Trento, Ctr Mind Brain Sci, Trento, Italy. [Venuti, Paola; de Pisapia, Nicola; Serra, Mauro; Esposito, Gianluca; Rigo, Paola] Univ Trento, Dept Psychol & Cognit Sci, Trento, Italy. [Esposito, Gianluca] Nanyang Technol Univ, Div Psychol, Sch Humanities & Social Sci, Singapore 639798, Singapore. [Farneti, Alessandra] Free Univ Bolzano, Dept Educ, Bolzano, Italy. [Bornstein, Marc H.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Child & Family Res, Bethesda, MD USA. RP Messina, I (reprint author), Univ Padua, Dept Philosophy Sociol Educ & Appl Psychol, Padua, Italy. EM irene-messina@hotmail.com OI De Pisapia, Nicola/0000-0002-1089-8841 FU Intramural Research Program of the NIH, NICHD FX We thank Dr Olivier Collignon for the realization of scrambled sounds for the control experiment. This research was supported by the Intramural Research Program of the NIH, NICHD. NR 98 TC 2 Z9 2 U1 4 U2 11 PU FRONTIERS MEDIA SA PI LAUSANNE PA PO BOX 110, EPFL INNOVATION PARK, BUILDING I, LAUSANNE, 1015, SWITZERLAND SN 1664-1078 J9 FRONT PSYCHOL JI Front. Psychol. PD JAN 7 PY 2016 VL 6 AR 1909 DI 10.3389/fpsyg.2015.01909 PG 10 WC Psychology, Multidisciplinary SC Psychology GA DA3ZN UT WOS:000367740000001 ER PT J AU Costa, VD Rudebeck, PH AF Costa, Vincent D. Rudebeck, Peter H. TI More than Meets the Eye: the Relationship between Pupil Size and Locus Coeruleus Activity SO NEURON LA English DT Editorial Material ID AROUSAL; ACTIVATION; NEURONS; MONKEYS; BRAIN; GAIN AB Using both direct neural recordings and electrical microstimulation, Joshi et al. (2016) show that locus coeruleus (LC) activity closely matches moment-to-moment changes in pupil size. But what causes these two measures to be related is not straightforward. C1 [Costa, Vincent D.] NIMH, Bethesda, MD 20814 USA. [Rudebeck, Peter H.] Icahn Sch Med Mt Sinai, Friedman Brain Inst, New York, NY 10029 USA. RP Costa, VD (reprint author), NIMH, Bethesda, MD 20814 USA.; Rudebeck, PH (reprint author), Icahn Sch Med Mt Sinai, Friedman Brain Inst, New York, NY 10029 USA. EM vincent.costa@nih.gov; peter.rudebeck@mssm.edu OI Rudebeck, Peter/0000-0002-1411-7555; Costa, Vincent/0000-0002-5412-8945 FU Intramural NIH HHS [Z99 MH999999] NR 12 TC 3 Z9 3 U1 2 U2 7 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 0896-6273 EI 1097-4199 J9 NEURON JI Neuron PD JAN 6 PY 2016 VL 89 IS 1 BP 8 EP 10 DI 10.1016/j.neuron.2015.12.031 PG 3 WC Neurosciences SC Neurosciences & Neurology GA DI5TV UT WOS:000373564300004 PM 26748086 ER PT J AU McGill, LA Ferreira, PF Scott, AD Nielles-Vallespin, S Giannakidis, A Kilner, PJ Gatehouse, PD de Silva, R Firmin, DN Pennell, DJ AF McGill, L. A. Ferreira, P. F. Scott, A. D. Nielles-Vallespin, S. Giannakidis, A. Kilner, P. J. Gatehouse, P. D. de Silva, R. Firmin, D. N. Pennell, D. J. TI Relationship between cardiac diffusion tensor imaging parameters and anthropometrics in healthy volunteers SO JOURNAL OF CARDIOVASCULAR MAGNETIC RESONANCE LA English DT Article DE Diffusion tensor imaging; Fractional anisotropy; Mean diffusivity; Eigenvector; Helix angle; Helix angle gradient; Sheetlet ID CARDIOVASCULAR MAGNETIC-RESONANCE; CANINE LEFT-VENTRICLE; IN-VIVO; HISTOLOGICAL VALIDATION; HYPERTROPHIC CARDIOMYOPATHY; MYOCARDIAL MICROSTRUCTURE; FIBER ARCHITECTURE; DIASTOLIC FUNCTION; LAMINAR STRUCTURE; SARCOMERE-LENGTH AB Background: In vivo cardiac diffusion tensor imaging (cDTI) is uniquely capable of interrogating laminar myocardial dynamics non-invasively. A comprehensive dataset of quantative parameters and comparison with subject anthropometrics is required. Methods: cDTI was performed at 3T with a diffusion weighted STEAM sequence. Data was acquired from the mid left ventricle in 43 subjects during the systolic and diastolic pauses. Global and regional values were determined for fractional anisotropy (FA), mean diffusivity (MD), helix angle gradient (HAg, degrees/% depth) and the secondary eigenvector angulation (E2A). Regression analysis was performed between global values and subject anthropometrics. Results: All cDTI parameters displayed regional heterogeneity. The RR interval had a significant, but clinically small effect on systolic values for FA, HAg and E2A. Male sex and increasing left ventricular end diastolic volume were associated with increased systolic HAg. Diastolic HAg and systolic E2A were both directly related to left ventricular mass and body surface area. There was an inverse relationship between E2A mobility and both age and ejection fraction. Conclusions: Future interpretations of quantitative cDTI data should take into account anthropometric variations observed with patient age, body surface area and left ventricular measurements. Further work determining the impact of technical factors such as strain and SNR is required. C1 [McGill, L. A.; Ferreira, P. F.; Scott, A. D.; Nielles-Vallespin, S.; Giannakidis, A.; Kilner, P. J.; Gatehouse, P. D.; de Silva, R.; Firmin, D. N.; Pennell, D. J.] Royal Brompton Hosp, NIHR Cardiovasc Biomed Res Unit, Sydney St, London SW3 6NP, England. [McGill, L. A.; Ferreira, P. F.; Scott, A. D.; Giannakidis, A.; Kilner, P. J.; Gatehouse, P. D.; de Silva, R.; Firmin, D. N.; Pennell, D. J.] Univ London Imperial Coll Sci Technol & Med, Natl Heart & Lung Inst, London, England. [Nielles-Vallespin, S.] NHLBI, NIH, Bldg 10, Bethesda, MD 20892 USA. RP Pennell, DJ (reprint author), Royal Brompton Hosp, NIHR Cardiovasc Biomed Res Unit, Sydney St, London SW3 6NP, England.; Pennell, DJ (reprint author), Univ London Imperial Coll Sci Technol & Med, Natl Heart & Lung Inst, London, England. EM dj.pennell@rbht.nhs.uk FU National Institute for Health Research Cardiovascular Biomedical Research Unit at The Royal Brompton Hospital and Imperial College London FX This work was performed at the National Institute for Health Research Cardiovascular Biomedical Research Unit at The Royal Brompton Hospital and Imperial College London. NR 51 TC 0 Z9 1 U1 4 U2 7 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1097-6647 EI 1532-429X J9 J CARDIOVASC MAGN R JI J. Cardiov. Magn. Reson. PD JAN 6 PY 2016 VL 18 AR 2 DI 10.1186/s12968-015-0215-0 PG 10 WC Cardiac & Cardiovascular Systems; Radiology, Nuclear Medicine & Medical Imaging SC Cardiovascular System & Cardiology; Radiology, Nuclear Medicine & Medical Imaging GA DB8XD UT WOS:000368799600001 PM 26738482 ER PT J AU Cavanaugh, J Berman, RA Joiner, WM Wurtz, RH AF Cavanaugh, James Berman, Rebecca A. Joiner, Wilsaan M. Wurtz, Robert H. TI Saccadic Corollary Discharge Underlies Stable Visual Perception SO JOURNAL OF NEUROSCIENCE LA English DT Article DE corollary discharge; efference copy; FEF; macaque; MD; visual perception ID FRONTAL EYE FIELD; BRAIN-STEM TELLS; SUPERIOR COLLICULUS; SOMATOSENSORY CORTEX; POSITION INFORMATION; RECEPTIVE-FIELDS; RHESUS-MONKEY; SIGNALS SENT; TIME-COURSE; MOVEMENTS AB Saccadic eye movements direct the high-resolution foveae of our retinas toward objects of interest. With each saccade, the image jumps on the retina, causing a discontinuity in visual input. Our visual perception, however, remains stable. Philosophers and scientists over centuries have proposed that visual stability depends upon an internal neuronal signal that is a copy of the neuronal signal driving the eye movement, now referred to as a corollary discharge (CD) or efference copy. In the old world monkey, such a CD circuit for saccades has been identified extending from superior colliculus through MD thalamus to frontal cortex, but there is little evidence that this circuit actually contributes to visual perception. We tested the influence of this CD circuit on visual perception by first training macaque monkeys to report their perceived eye direction, and then reversibly inactivating the CD as it passes through the thalamus. We found that the monkey's perception changed; during CD inactivation, there was a difference between where the monkey perceived its eyes to be directed and where they were actually directed. Perception and saccade were decoupled. We established that the perceived eye direction at the end of the saccade was not derived from proprioceptive input from eye muscles, and was not altered by contextual visual information. We conclude that the CD provides internal information contributing to the brain's creation of perceived visual stability. More specifically, the CD might provide the internal saccade vector used to unite separate retinal images into a stable visual scene. C1 [Cavanaugh, James; Berman, Rebecca A.; Joiner, Wilsaan M.; Wurtz, Robert H.] NEI, Sensorimotor Res Lab, NIH, Bethesda, MD 20892 USA. RP Cavanaugh, J (reprint author), NEI, Sensorimotor Res Lab, Bldg 49,Room 2A50, Bethesda, MD 20892 USA. EM jrc@lsr.nei.nih.gov FU National Eye Institute Intramural Research Program at the National Institutes of Health FX This work was supported by the National Eye Institute Intramural Research Program at the National Institutes of Health. We thank Altah Nichols and Tom Ruffner for machine shop support, David Leopold and Frank Ye for advice on analysis of the MRIs, and two anonymous reviewers whose analysis suggestions have strengthened our findings. NR 62 TC 10 Z9 10 U1 1 U2 8 PU SOC NEUROSCIENCE PI WASHINGTON PA 11 DUPONT CIRCLE, NW, STE 500, WASHINGTON, DC 20036 USA SN 0270-6474 J9 J NEUROSCI JI J. Neurosci. PD JAN 6 PY 2016 VL 36 IS 1 BP 31 EP 42 DI 10.1523/JNEUROSCI.2054-15.2016 PG 12 WC Neurosciences SC Neurosciences & Neurology GA DB2OE UT WOS:000368348100007 PM 26740647 ER PT J AU Matsumoto, N Eldridge, MAG Saunders, RC Reoli, R Richmond, BJ AF Matsumoto, Narihisa Eldridge, Mark A. G. Saunders, Richard C. Reoli, Rachel Richmond, Barry J. TI Mild Perceptual Categorization Deficits Follow Bilateral Removal of Anterior Inferior Temporal Cortex in Rhesus Monkeys SO JOURNAL OF NEUROSCIENCE LA English DT Article DE behavior; categorization; generalization; lesion; perception ID FACE-RESPONSIVE NEURONS; MACAQUE CEREBRAL-CORTEX; VENTRAL VISUAL PATHWAY; INFEROTEMPORAL CORTEX; OBJECT RECOGNITION; PERIRHINAL CORTEX; PREFRONTAL CORTEX; AREA TE; VISION; MODEL AB In primates, visual recognition of complex objects depends on the inferior temporal lobe. By extension, categorizing visual stimuli based on similarity ought to depend on the integrity of the same area. We tested three monkeys before and after bilateral anterior inferior temporal cortex (area TE) removal. Although mildly impaired after the removals, they retained the ability to assign stimuli to previously learned categories, e.g., cats versus dogs, and human versus monkey faces, even with trial-unique exemplars. After the TE removals, they learned in one session to classify members from a new pair of categories, cars versus trucks, as quickly as they had learned the cats versus dogs before the removals. As with the dogs and cats, they generalized across trial-unique exemplars of cars and trucks. However, as seen in earlier studies, these monkeys with TE removals had difficulty learning to discriminate between two simple black and white stimuli. These results raise the possibility that TE is needed for memory of simple conjunctions of basic features, but that it plays only a small role in generalizing overall configural similarity across a large set of stimuli, such as would be needed for perceptual categorical assignment. C1 [Matsumoto, Narihisa] Natl Inst Adv Ind Sci & Technol, Human Informat Res Inst, Tsukuba, Ibaraki 3058568, Japan. [Matsumoto, Narihisa; Eldridge, Mark A. G.; Saunders, Richard C.; Reoli, Rachel; Richmond, Barry J.] NIMH, Neuropsychol Lab, NIH, Bethesda, MD 20892 USA. RP Richmond, BJ (reprint author), NIMH, Neuropsychol Lab, Bldg 49,Room 1B80,9000 Rockville Pike, Bethesda, MD 20892 USA. EM bjr@ln.nimh.nih.gov FU National Institute of Advanced Industrial Science and Technology; Intramural Research Program of the National Institute of Mental Health; Japan Society for the Promotion of Science FX This work was supported by the National Institute of Advanced Industrial Science and Technology (N.M.), the Intramural Research Program of the National Institute of Mental Health (N.M., M.A.G.E., R.C.S., R.R., B.J.R.), and Japan Society for the Promotion of Science (N.M., B.J.R.). The views expressed in this article do not necessarily represent the views of the NIMH, NIH, or the U.S. government. We thank A. Young, A. Horovitz, and M. Malloy for their technical help. We also thank Drs. S. Bouret, J. Wittig, A. Clark, W. Lercher, J. Simmons, Y. Sugase-Miyamoto, and K. Gothard for their useful discussions. We thank Dr. K. Gothard for providing photos of monkey faces. NR 46 TC 0 Z9 0 U1 2 U2 6 PU SOC NEUROSCIENCE PI WASHINGTON PA 11 DUPONT CIRCLE, NW, STE 500, WASHINGTON, DC 20036 USA SN 0270-6474 J9 J NEUROSCI JI J. Neurosci. PD JAN 6 PY 2016 VL 36 IS 1 BP 43 EP 53 DI 10.1523/JNEUROSCI.2058-15.2016 PG 11 WC Neurosciences SC Neurosciences & Neurology GA DB2OE UT WOS:000368348100008 PM 26740648 ER PT J AU Xu, Y Shugart, YY Wang, GQ Cheng, ZH Jin, CH Zhang, K Wang, J Yu, H Yue, WH Zhang, FQ Zhang, D AF Xu, Yong Shugart, Yin Yao Wang, Guoqiang Cheng, Zaohuo Jin, Chunhui Zhang, Kai Wang, Jun Yu, Hao Yue, Weihua Zhang, Fuquan Zhang, Dai TI Altered expression of mRNA profiles in blood of early-onset schizophrenia SO SCIENTIFIC REPORTS LA English DT Article ID GENE COEXPRESSION NETWORKS; SIGNALING PATHWAYS; MUTANT MICE; CTLA4 GENE; POLYMORPHISM; BRAIN; MICROARRAY; PROTEIN; ABNORMALITIES; ASSOCIATION AB To identify gene expression abnormalities in schizophrenia (SZ), we generated whole-genome gene expression profiles using microarrays on peripheral blood mononuclear cells (PBMCs) from 18 early-onset SZ cases and 12 controls. We detected 84 transcripts differentially expressed by diagnostic status, with 82 genes being upregulated and 2 downregulated. We identified two SZ associated gene coexpression modules (green and red), including 446 genes. The green module is positively correlated with SZ, encompassing predominantly up-regulated genes in SZ; while the red module was negatively correlated with disease status, involving mostly nominally down-regulated genes in SZ. The olfactory transduction pathway was the most enriched pathways for the genes within the two modules. The expression levels of several hub genes, including AKT1, BRCA1, CCDC134, UBD, and ZIC2 were validated using real-time quantitative PCR. Our findings indicate that mRNA coexpression abnormalities may serve as a promising mechanism underlying the development of SZ. C1 [Xu, Yong] Shanxi Med Univ, Clin Med Coll 1, Hosp 1, Dept Psychiat, Taiyuan, Peoples R China. [Shugart, Yin Yao] NIMH, Unit Stat Genom, Div Intramural Res Program, NIH, Bethesda, MD 20892 USA. [Wang, Guoqiang; Cheng, Zaohuo; Jin, Chunhui; Zhang, Kai; Wang, Jun; Zhang, Fuquan] Nanjing Med Univ, Wuxi Mental Hlth Ctr, Wuxi, Jiangsu, Peoples R China. [Yu, Hao; Yue, Weihua; Zhang, Dai] Peking Univ, Hosp 6, Inst Mental Hlth, Beijing 100191, Peoples R China. [Yu, Hao; Yue, Weihua; Zhang, Dai] Peking Univ, Key Lab Mental Hlth, Minist Hlth, Beijing 100191, Peoples R China. [Yu, Hao; Yue, Weihua; Zhang, Dai] Peking Univ, Natl Clin Res Ctr Mental Disorders, Beijing 100191, Peoples R China. [Zhang, Dai] Peking Univ, Peking Tsinghua Ctr Life Sci, PKU IDG McGovern Inst Brain Res, Beijing 100871, Peoples R China. RP Yue, WH (reprint author), Nanjing Med Univ, Wuxi Mental Hlth Ctr, Wuxi, Jiangsu, Peoples R China. EM dryue@bjmu.edu.cn; zhangfq@njmu.edu.cn FU National Natural Science Foundation of China [81471364, 81271482, 81571319]; Beijing Natural Science Foundation [7132182]; Program for New Century Excellent Talents in University [NCET-12-1036]; Intramural Research Program of National Institute of Mental Health, National Institutes of Health [MH002929-05] FX We sincerely thank all the subjects for their support and participation and all the medical staff involved in collecting blood samples. We thank Chunyu Liu and Simone de Jong for their help in the manuscript writing. This work was supported by the National Natural Science Foundation of China (81471364, 81271482, 81571319), Beijing Natural Science Foundation (7132182), Program for New Century Excellent Talents in University (NCET-12-1036). Shugart was supported by the Intramural Research Program of National Institute of Mental Health, National Institutes of Health (MH002929-05). NR 61 TC 2 Z9 2 U1 4 U2 24 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 JAN 6 PY 2016 VL 6 AR 16767 DI 10.1038/srep16767 PG 10 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA DB0ZY UT WOS:000368238800001 PM 26733343 ER PT J AU Kim, J Staunton, JR Tanner, K AF Kim, Jiyun Staunton, Jack Rory Tanner, Kandice TI Independent Control of Topography for 3D Patterning of the ECM Microenvironment SO ADVANCED MATERIALS LA English DT Article ID STEM-CELL FATE; PEPTIDE-AMPHIPHILE NANOFIBERS; EXTRACELLULAR-MATRIX; MECHANOTRANSDUCTION; NANOTOPOGRAPHY; MIGRATION; TISSUES; MOTION AB Biomimetic extracellular matrix (ECM) topographies driven by the magneticfield-directed self-assembly of ECM protein-coated magnetic beads are fabricated. This novel bottom-up method allows us to program isotropic, anisotropic, and diverse hybrid ECM patterns without changing other physicochemical properties of the scaffold material. It is demonstrated that this 3D anisotropic matrix is able to guide the dendritic protrusion of cells. C1 [Kim, Jiyun; Staunton, Jack Rory; Tanner, Kandice] NCI, Cell Biol Lab, Ctr Canc Res, NIH, Bethesda, MD 20852 USA. RP Tanner, K (reprint author), NCI, Cell Biol Lab, Ctr Canc Res, NIH, Bethesda, MD 20852 USA. EM kandice.tanner@nih.gov FU Intramural Research Program of the National Institutes of Health, the National Cancer Institute; Korea Health Technology R&D Project through the Korea Health Industry Development Institute (KHIDI) - Ministry of Health & Welfare, Republic of Korea [HI14C1161] FX This research was supported by the Intramural Research Program of the National Institutes of Health, the National Cancer Institute. The work was also supported by a grant of the Korea Health Technology R&D Project through the Korea Health Industry Development Institute (KHIDI), funded by the Ministry of Health & Welfare, Republic of Korea (Grant No. HI14C1161). The authors thank George Leiman for critically reading this paper. NR 36 TC 3 Z9 3 U1 12 U2 32 PU WILEY-V C H VERLAG GMBH PI WEINHEIM PA POSTFACH 101161, 69451 WEINHEIM, GERMANY SN 0935-9648 EI 1521-4095 J9 ADV MATER JI Adv. Mater. PD JAN 6 PY 2016 VL 28 IS 1 BP 132 EP + DI 10.1002/adma.201503950 PG 7 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 DA5KD UT WOS:000367841100016 PM 26551393 ER PT J AU Arolas, JL Goulas, T Pomerantsev, AP Leppla, SH Gomis-Ruth, FX AF Arolas, Joan L. Goulas, Theodoros Pomerantsev, Andrei P. Leppla, Stephen H. Xavier Gomis-Rueth, F. TI Structural Basis for Latency and Function of Immune Inhibitor A Metallopeptidase, a Modulator of the Bacillus anthracis Secretome SO STRUCTURE LA English DT Article ID AB(5) TOXINS; CRYSTAL-STRUCTURE; CATALYTIC DOMAIN; DATA QUALITY; MECHANISM; METALLOPROTEASE; PROTEINS; THURINGIENSIS; PROTEASE; CEREUS AB Immune inhibitor A(InhA)-type metallopeptidases are potential virulence factors secreted by members of the Bacillus cereus group. Two paralogs from anthrax-causing Bacillus anthracis (BaInhA1 and BaInhA2) were shown to degrade host tissue proteins with broad substrate specificity. Analysis of their activation mechanism and the crystal structure of a zymogenic BaInhA2 variant revealed a similar to 750-residue four-domain structure featuring a pro-peptide, a catalytic domain, a domain reminiscent of viral envelope glycoproteins, and a MAM domain grafted into the latter. This domain, previously found only in eukaryotes, is required for proper protein expression in B. anthracis and evinces certain flexibility. Latency is uniquely modulated by the N-terminal segment of the pro-peptide, which binds the catalytic zinc through its a-amino group and occupies the primed side of the active-site cleft. The present results further our understanding of the modus operandi of an anthrax secretome regulator. C1 [Arolas, Joan L.; Goulas, Theodoros; Xavier Gomis-Rueth, F.] Spanish Res Council CSIC, Mol Biol Inst Barcelona, Dept Biol Struct, Maria de Maeztu Unit Excellence,Proteolysis Lab, Barcelona Sci Pk,Helix Bldg,Baldiri Reixac 15-21, Barcelona 08028, Spain. [Pomerantsev, Andrei P.; Leppla, Stephen H.] NIAID, Parasit Dis Lab, NIH, Bethesda, MD 20892 USA. [Arolas, Joan L.] Univ Vienna, Dept Struct & Computat Biol, Max F Perutz Labs, Campus Vienna Bioctr 5, A-1030 Vienna, Austria. RP Gomis-Ruth, FX (reprint author), Spanish Res Council CSIC, Mol Biol Inst Barcelona, Dept Biol Struct, Maria de Maeztu Unit Excellence,Proteolysis Lab, Barcelona Sci Pk,Helix Bldg,Baldiri Reixac 15-21, Barcelona 08028, Spain. EM xgrcri@ibmb.csic.es RI Goulas, Theodoros/H-1951-2015; OI Goulas, Theodoros/0000-0002-6938-5493 FU National Institute of Allergy and Infectious Diseases, NIH; ESRF; [FP7-PEOPLE-2011-ITN-290246 "RAPID'']; [FP7-HEALTH-2012-306029-2 "TRIGGER'']; [BFU2012-32862; BFU2015-64487R]; [MDM-2014-0435]; [BIO2013-49320-EXP]; [2014SGR9] FX We thank Tibisay Guevara, Joan Pous, and Xandra Kreplin (the latter two from the IBMB/IRB Protein Crystallography Platform) for excellent technical assistance during crystallization experiments, and Mar Lopez Pelegrin and Isabel Uson for help with purification experiments and diffraction data collection, respectively. Robin Rycroft is thanked for critical reading of the manuscript. We are indebted to Euripedes de Almeida Ribeiro and Kristina Djinovic-Carugo (both at University of Vienna, Austria), as well as Pau Bernado (University of Montpellier, France) for excellent guidance on SAXS data analysis. We are also grateful to Hideaki Nagase (University of Oxford, UK), Gunnar Hansson (University of Gothenburg, Sweden), and Lars Sottrup-Jensen (Aarhus University, Denmark) for generous gifts of collagen, mucin, and alpha2M, respectively. This study was supported in part by grants from European, Spanish, and Catalan agencies (FP7-PEOPLE-2011-ITN-290246 "RAPID''; FP7-HEALTH-2012-306029-2 "TRIGGER''; BFU2012-32862; BFU2015-64487R; MDM-2014-0435; BIO2013-49320-EXP; and 2014SGR9), and by the intramural program of the National Institute of Allergy and Infectious Diseases, NIH. The Department of Structural Biology of IBMB is a "Maria de Maeztu'' Unit of Excellence of the Spanish Ministry of Economy and Competitiveness. We acknowledge the help provided by ESRF and ALBA synchrotron local contacts. Funding for traveling and synchrotron data collection was provided in part by ESRF. NR 44 TC 1 Z9 1 U1 1 U2 3 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 0969-2126 EI 1878-4186 J9 STRUCTURE JI Structure PD JAN 5 PY 2016 VL 24 IS 1 BP 25 EP 36 DI 10.1016/j.str.2015.10.015 PG 12 WC Biochemistry & Molecular Biology; Biophysics; Cell Biology SC Biochemistry & Molecular Biology; Biophysics; Cell Biology GA DI5UQ UT WOS:000373566400005 PM 26745529 ER PT J AU Grinman, DY Romorini, L Presman, DM Rocha-Viegas, L Coso, OA Davio, C Pecci, A AF Grinman, Diego Y. Romorini, Leonardo Presman, Diego M. Rocha-Viegas, Luciana Coso, Omar A. Davio, Carlos Pecci, Adali TI Role of 3 '-5 '-cyclic adenosine monophosphate on the epidermal growth factor dependent survival in mammary epithelial cells SO MOLECULAR AND CELLULAR ENDOCRINOLOGY LA English DT Article DE Mammary epithelial cells; bcl-X; Apoptosis; EGF; cAMP; CREB ID BCL-X GENE; ELEMENT-BINDING PROTEIN; FACTOR RECEPTOR; BREAST-CANCER; APOPTOSIS RESISTANCE; GLAND DEVELOPMENT; UP-REGULATION; MOUSE MILK; ACTIVATION; EXPRESSION AB Epidermal growth factor (EGF) has been suggested to play a key role in the maintenance of epithelial cell survival during lactation. Previously, we demonstrated that EGF dependent activation of PI3K pathway prevents apoptosis in confluent murine HC11 cells cultured under low nutrient conditions. The EGF protective effect is associated with increased levels of the antiapoptotic protein Bcl-XL. Here, we identify the EGF-dependent mechanism involved in cell survival that converges in the regulation of bcl-X expression by activated CREB. EGF induces Bcl-XL expression through activation of a unique bcl-X promoter, the P1; being not only the PI3K/ART signaling pathway but also the increase in cAMP levels and the concomitant PICA/CREB activation necessary for both bcl-XL upregulation and apoptosis avoidance. Results presented in this work suggest the existence of a novel connection between the EGF receptor and the adenylate cyclase that would have an impact in preventing apoptosis under low nutrient conditions. (C) 2015 Elsevier Ireland Ltd. All rights reserved. C1 [Grinman, Diego Y.; Pecci, Adali] Univ Buenos Aires, Dept Quim Biol, Intendente Guiraldes 2160,Ciudad Univ,C1428EGA, Buenos Aires, DF, Argentina. [Rocha-Viegas, Luciana; Coso, Omar A.] Univ Buenos Aires, Dept Fisiol Biol Mol & Celular, Intendente Guiraldes 2160,Ciudad Univ,C1428EGA, Buenos Aires, DF, Argentina. [Grinman, Diego Y.; Rocha-Viegas, Luciana; Coso, Omar A.; Pecci, Adali] Univ Buenos Aires, Fac Ciencias Exactas & Nat, CONICET, IFIBYNE, Intendente Guiraldes 2160,Ciudad Univ,C1428EGA, Buenos Aires, DF, Argentina. [Romorini, Leonardo] Fdn Lucha Enfermedades Neurodegenerat Infancia, CONICET, LIAN, Ruta 9,Km 52,5,B1625XAF, Escobar, Buenos Aires, Argentina. [Davio, Carlos] Univ Buenos Aires, Fac Farm & Bioquim, Dept Farmacol, Catedra Quim Med, RA-1053 Buenos Aires, DF, Argentina. [Davio, Carlos] UBA, CONICET, Inst Invest Farmacol, ININFA, Junin 954,C1113AAD, Buenos Aires, DF, Argentina. [Presman, Diego M.] NCI, Lab Receptor Biol & Gene Express, NIH, Bldg 41,B602,41 Lib Dr, Bethesda, MD 20892 USA. RP Pecci, A (reprint author), Univ Buenos Aires, Fac Ciencias Exactas & Nat, Intendente Guiraldes 2160,Ciudad Univ, Buenos Aires, DF, Argentina. EM apecci@qb.fcen.uba.ar OI Grinman, Diego/0000-0003-0086-2957; Presman, Diego/0000-0003-4515-8058 FU University of Buenos Aires [20020130100363BA]; National Agency of Scientific Promotion of Argentina [BID-2011 PICT 1321] FX This work was supported by grants from the University of Buenos Aires [20020130100363BA] and the National Agency of Scientific Promotion of Argentina [BID-2011 PICT 1321]. NR 56 TC 0 Z9 0 U1 1 U2 1 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0303-7207 J9 MOL CELL ENDOCRINOL JI Mol. Cell. Endocrinol. PD JAN 5 PY 2016 VL 419 IS C BP 259 EP 267 DI 10.1016/j.mce.2015.10.026 PG 9 WC Cell Biology; Endocrinology & Metabolism SC Cell Biology; Endocrinology & Metabolism GA DE9WX UT WOS:000370991700026 PM 26522133 ER PT J AU de Messieres, M Ng, A Duarte, CJ Remaley, AT Lee, JC AF de Messieres, Michel Ng, Abby Duarte, Cornelio J. Remaley, Alan T. Lee, Jennifer C. TI Single-Particle Tracking of Human Lipoproteins SO ANALYTICAL CHEMISTRY LA English DT Article ID CARDIOVASCULAR-DISEASE; SUBFRACTIONS; RISK; HDL AB Lipoproteins, such as high-density lipoprotein (HDL), low-density lipoprotein (LDL), and very-low density lipoprotein (VLDL), play a critical role in heart disease. Lipoproteins vary in size and shape as well as in their apolipoprotein content. Here, we developed a new experimental framework to study freely diffusing lipoproteins from human blood, allowing analysis of even the smallest HDL with a radius of 5 nm. In an easily constructed confinement chamber, individual HDL, LDL, and VLDL particles labeled with three distinct fluorophores were simultaneously tracked by wide-field fluorescence microscopy and their sizes were determined by their motion. This technique enables studies of individual lipoproteins in solution and allows characterization of the heterogeneous properties of lipoproteins which affect their biological function but are difficult to discern in bulk studies. C1 [de Messieres, Michel; Ng, Abby; Lee, Jennifer C.] NHLBI, Lab Mol Biophys, NIH, Bethesda, MD 20892 USA. [Duarte, Cornelio J.; Remaley, Alan T.] NHLBI, Lipoprot Metab Sect, NIH, Bethesda, MD 20892 USA. RP Lee, JC (reprint author), NHLBI, Lab Mol Biophys, NIH, Bldg 10, Bethesda, MD 20892 USA. EM leej4@mail.nih.gov RI Lee, Jennifer/E-9658-2015 OI Lee, Jennifer/0000-0003-0506-8349 FU Intramural Research Program at the National Institutes of Health, National Heart, Lung, and Blood Institute FX Supported by the Intramural Research Program at the National Institutes of Health, National Heart, Lung, and Blood Institute. Wide-field microscopy, TEM, and DLS were collected in the NHLBI Light Microscopy, EM, and Biophysics Core Facilities, respectively. NR 21 TC 0 Z9 0 U1 0 U2 7 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0003-2700 EI 1520-6882 J9 ANAL CHEM JI Anal. Chem. PD JAN 5 PY 2016 VL 88 IS 1 BP 596 EP 599 DI 10.1021/acs.analchem.5b03749 PG 4 WC Chemistry, Analytical SC Chemistry GA DA5TS UT WOS:000367866100031 PM 26643517 ER PT J AU Peng, YQ Kim, JM Park, HS Yang, A Islam, C Lakatta, EG Lin, L AF Peng, Yunqian Kim, Ji-Min Park, Hal-Sol Yang, Annie Islam, Celia Lakatta, Edward G. Lin, Li TI AGE-RAGE signal generates a specific NF-kappa B RelA "barcode" that directs collagen I expression SO SCIENTIFIC REPORTS LA English DT Article ID GLYCATION END-PRODUCTS; S6 KINASE; POSTTRANSLATIONAL MODIFICATIONS; TRANSCRIPTIONAL ACTIVATION; GENE-TRANSCRIPTION; HUMAN-FIBROBLASTS; IKK-EPSILON; P65; PHOSPHORYLATION; RECEPTOR AB Advanced glycation end products (AGEs) are sugar-modified biomolecules that accumulate in the body with advancing age, and are implicated in the development of multiple age-associated structural and functional abnormities and diseases. It has been well documented that AGEs signal via their receptor RAGE to activate several cellular programs including NF-kappa B, leading to inflammation. A large number of stimuli can activate NF-kappa B; yet different stimuli, or the same stimulus for NF-kappa B in different cellular settings, produce a very different transcriptional landscape and physiological outcome. The NF-kappa B barcode hypothesis posits that cellular network dynamics generate signal-specific post-translational modifications, or a "barcode" to NF-kappa B, and that a signature "barcode" mediates a specific gene expression pattern. In the current study, we established that AGE-RAGE signaling results in NF-kappa B activation that directs collagen Ia1 and Ia2 expression. We further demonstrated that AGE-RAGE signal induces phosphorylation of RelA at three specific residues, T254, S311, and S536. These modifications are required for transcription of collagen I genes and are a consequence of cellular network dynamics. The increase of collagen content is a hallmark of arterial aging, and our work provides a potential mechanistic link between RAGE signaling, NF-kappa B activation, and aging-associated arterial alterations in structure and function. C1 [Peng, Yunqian; Kim, Ji-Min; Park, Hal-Sol; Yang, Annie; Islam, Celia; Lakatta, Edward G.; Lin, Li] NIA, Lab Cardiovasc Sci, NIH, Baltimore, MD 21224 USA. RP Lin, L (reprint author), NIA, Lab Cardiovasc Sci, NIH, Baltimore, MD 21224 USA. EM linli@mail.nih.gov FU intramural research program of National Institute on Aging, NIH FX This work is supported by the intramural research program of National Institute on Aging, NIH. We thank Dr. Yosef Anrather (Weil Medical College) for RelA-null and wild-type MEFs, Dr. Amer Beg (Moffitt Cancer Center) for the permission to use RelA-null MEFs, and Dr. Angelika Bierhaus (Heidelberg University) for RAGE-null mice. We also thank NIA colleagues Dr. Mingyi Wang for monkey artery sections, Dr. Christopher Morrell for the advice on statistical analyses. NR 61 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 JAN 5 PY 2016 VL 6 AR 18822 DI 10.1038/srep18822 PG 10 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA DB2YM UT WOS:000368376600001 PM 26729520 ER PT J AU Lyman, E Sodt, AJ AF Lyman, Edward Sodt, Alexander J. TI Amphipathic Helices-Wedge? Or Nae Nae? SO BIOPHYSICAL JOURNAL LA English DT News Item ID CURVATURE INDUCTION C1 [Lyman, Edward] Univ Delaware, Dept Phys & Astron, Newark, DE 19716 USA. [Lyman, Edward] Univ Delaware, Dept Chem & Biochem, Newark, DE 19716 USA. [Sodt, Alexander J.] NHLBI, NIH, Bethesda, MD 20892 USA. RP Lyman, E (reprint author), Univ Delaware, Dept Phys & Astron, Newark, DE 19716 USA. EM elyman@udel.edu FU NIGMS NIH HHS [P20 GM104316] NR 10 TC 0 Z9 0 U1 4 U2 10 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 0006-3495 EI 1542-0086 J9 BIOPHYS J JI Biophys. J. PD JAN 5 PY 2016 VL 110 IS 1 BP 1 EP 2 DI 10.1016/j.bpj.2015.11.3513 PG 2 WC Biophysics SC Biophysics GA DA4QD UT WOS:000367783900004 PM 26745402 ER PT J AU Ma, J Zhao, HY Sandmaier, J Liddle, JA Schuck, P AF Ma, Jia Zhao, Huaying Sandmaier, Julia Liddle, J. Alexander Schuck, Peter TI Variable Field Analytical Ultracentrifugation: II. Gravitational Sweep Sedimentation Velocity SO BIOPHYSICAL JOURNAL LA English DT Article ID PARTICLE-SIZE DISTRIBUTION; LAMM EQUATION; DISTRIBUTIONS; ACCURACY; SYSTEMS; SPEED AB Sedimentation velocity (SV) analytical ultracentrifugation is a classical biophysical technique for the determination of the size-distribution of macromolecules, macromolecular complexes, and nanoparticles. SV has traditionally been carried out at a constant rotor speed, which limits the range of sedimentation coefficients that can be detected in a single experiment. Recently we have introduced methods to implement experiments with variable rotor speeds, in combination with variable field solutions to the Lamm equation, with the application to expedite the approach to sedimentation equilibrium. Here, we describe the use of variable-field sedimentation analysis to increase the size-range covered in SV experiments by similar to 100-fold with a quasi-continuous increase of rotor speed during the experiment. Such a gravitational-sweep sedimentation approach has previously been shown to be very effective in the study of nanoparticles with large size ranges. In the past, diffusion processes were not accounted for, thereby posing a lower limit of particle sizes and limiting the accuracy of the size distribution. In this work, we combine variable field solutions to the Lamm equation with diffusion-deconvoluted sedimentation coefficient distributions c(s), which further extend the macromolecular size range that can be observed in a single SV experiment while maintaining accuracy and resolution. In this way, approximately five orders of magnitude of sedimentation coefficients, or eight orders of magnitude of particle mass, can be probed in a single experiment. This can be useful, for example, in the study of proteins forming large assemblies, as in fibrillation process or capsid self-assembly, in studies of the interaction between very dissimilar-sized macromolecular species, or in the study of broadly distributed nanoparticles. C1 [Ma, Jia; Zhao, Huaying; Schuck, Peter] Natl Inst Biomed Imaging & Bioengn, Dynam Macromol Assembly Sect, Lab Cellular Imaging & Macromol Biophys, NIH, Bethesda, MD 20892 USA. [Sandmaier, Julia; Liddle, J. Alexander] NIST, Ctr Nanoscale Sci & Technol, Gaithersburg, MD 20899 USA. RP Schuck, P (reprint author), Natl Inst Biomed Imaging & Bioengn, Dynam Macromol Assembly Sect, Lab Cellular Imaging & Macromol Biophys, NIH, Bethesda, MD 20892 USA. EM schuckp@mail.nih.gov RI Liddle, James/A-4867-2013; OI Liddle, James/0000-0002-2508-7910; Schuck, Peter/0000-0002-8859-6966 FU Intramural Research Program of the National Institute of Biomedical Imaging and Bioengineering, National Institutes of Health, Bethesda, MD FX This work was supported by the Intramural Research Program of the National Institute of Biomedical Imaging and Bioengineering, National Institutes of Health, Bethesda, MD. NR 38 TC 2 Z9 2 U1 4 U2 15 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 0006-3495 EI 1542-0086 J9 BIOPHYS J JI Biophys. J. PD JAN 5 PY 2016 VL 110 IS 1 BP 103 EP 112 DI 10.1016/j.bpj.2015.11.027 PG 10 WC Biophysics SC Biophysics GA DA4QD UT WOS:000367783900002 PM 26745414 ER PT J AU Lin, YZ Golovnina, K Chen, ZX Lee, HN Negron, YLS Sultana, H Oliver, B Harbison, ST AF Lin, Yanzhu Golovnina, Kseniya Chen, Zhen-Xia Lee, Hang Noh Negron, Yazmin L. Serrano Sultana, Hina Oliver, Brian Harbison, Susan T. TI Comparison of normalization and differential expression analyses using RNA-Seq data from 726 individual Drosophila melanogaster SO BMC GENOMICS LA English DT Article DE RNA-Seq; Differential expression analysis; Drosophila melanogaster ID GENETIC REFERENCE PANEL; TRANSCRIPTOME; MICROARRAYS; VARIANCE; SEQUENCE; POWER AB Background: A generally accepted approach to the analysis of RNA-Seq read count data does not yet exist. We sequenced the mRNA of 726 individuals from the Drosophila Genetic Reference Panel in order to quantify differences in gene expression among single flies. One of our experimental goals was to identify the optimal analysis approach for the detection of differential gene expression among the factors we varied in the experiment: genotype, environment, sex, and their interactions. Here we evaluate three different filtering strategies, eight normalization methods, and two statistical approaches using our data set. We assessed differential gene expression among factors and performed a statistical power analysis using the eight biological replicates per genotype, environment, and sex in our data set. Results: We found that the most critical considerations for the analysis of RNA-Seq read count data were the normalization method, underlying data distribution assumption, and numbers of biological replicates, an observation consistent with previous RNA-Seq and microarray analysis comparisons. Some common normalization methods, such as Total Count, Quantile, and RPKM normalization, did not align the data across samples. Furthermore, analyses using the Median, Quantile, and Trimmed Mean of M-values normalization methods were sensitive to the removal of low-expressed genes from the data set. Although it is robust in many types of analysis, the normal data distribution assumption produced results vastly different than the negative binomial distribution. In addition, at least three biological replicates per condition were required in order to have sufficient statistical power to detect expression differences among the three-way interaction of genotype, environment, and sex. Conclusions: The best analysis approach to our data was to normalize the read counts using the DESeq method and apply a generalized linear model assuming a negative binomial distribution using either edgeR or DESeq software. Genes having very low read counts were removed after normalizing the data and fitting it to the negative binomial distribution. We describe the results of this evaluation and include recommended analysis strategies for RNA-Seq read count data. C1 [Lin, Yanzhu; Negron, Yazmin L. Serrano; Harbison, Susan T.] NHLBI, Lab Syst Genet, Ctr Syst Biol, Bethesda, MD 20892 USA. [Golovnina, Kseniya; Chen, Zhen-Xia; Lee, Hang Noh; Sultana, Hina; Oliver, Brian] NIDDK, Dev Genom Sect, Lab Cellular & Dev Biol, Bethesda, MD 20892 USA. RP Harbison, ST (reprint author), NHLBI, Lab Syst Genet, Ctr Syst Biol, 10 Ctr Dr,MSC 1640, Bethesda, MD 20892 USA. EM susan.harbison@nih.gov RI Harbison, Susan/P-2577-2016 OI Harbison, Susan/0000-0001-7233-0947 FU NIH, National Heart Lung and Blood Institute and National Institute of Diabetes and Digestive and Kidney Diseases FX This research was supported by the Intramural Research Program of the NIH, National Heart Lung and Blood Institute and National Institute of Diabetes and Digestive and Kidney Diseases. We thank the NIDDK and NHLBI sequencing cores for sequence data. We thank M.-A. Dillies for providing R code for normalization, and S. Anders, Y. Chen, W. Huber, M. Love, and G. K. Smyth for technical assistance. NR 54 TC 8 Z9 8 U1 7 U2 21 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 JAN 5 PY 2016 VL 17 AR 28 DI 10.1186/s12864-015-2353-z PG 20 WC Biotechnology & Applied Microbiology; Genetics & Heredity SC Biotechnology & Applied Microbiology; Genetics & Heredity GA DA1OY UT WOS:000367566300011 PM 26732976 ER PT J AU Powers, JH Guerrero, ML Leidy, NK Fairchok, MP Rosenberg, A Hernandez, A Stringer, S Schofield, C Rodriguez-Zulueta, P Kim, K Danaher, PJ Ortega-Gallegos, H Bacci, ED Stepp, N Galindo-Fraga, A St Clair, K Rajnik, M McDonough, EA Ridore, M Arnold, JC Millar, EV Ruiz-Palacios, GM AF Powers, John H. Guerrero, M. Lourdes Leidy, Nancy Kline Fairchok, Mary P. Rosenberg, Alice Hernandez, Andres Stringer, Sonja Schofield, Christina Rodriguez-Zulueta, Patricia Kim, Katherine Danaher, Patrick J. Ortega-Gallegos, Hilda Bacci, Elizabeth Dansie Stepp, Nathaniel Galindo-Fraga, Arturo St Clair, Kristina Rajnik, Michael McDonough, Erin A. Ridore, Michelande Arnold, John C. Millar, Eugene V. Ruiz-Palacios, Guillermo M. TI Development of the Flu-PRO: a patient-reported outcome (PRO) instrument to evaluate symptoms of influenza SO BMC INFECTIOUS DISEASES LA English DT Article DE Influenza; Symptoms; Patient-reported outcomes; Endpoints; Outcome assessments; Content validity ID TASK-FORCE REPORT; CONTENT VALIDITY AB Background: To develop content validity of a comprehensive patient-reported outcome (PRO) measure following current best scientific methodology to standardize assessment of influenza (flu) symptoms in clinical research. Methods: Stage I (Concept Elicitation): 1:1 telephone interviews with influenza-positive adults (>= 18 years) in the US and Mexico within 7 days of diagnosis. Participants described symptom type, character, severity, and duration. Content analysis identified themes and developed the draft Flu-PRO instrument. Stage II (Cognitive Interviewing): The Flu-PRO was administered to a unique set of influenza-positive adults within 14 days of diagnosis; telephone interviews addressed completeness, respondent interpretation of items and ease of use. Results: Samples: Stage I: N = 46 adults (16 US, 30 Mexico); mean (SD) age: 38 (19), 39 (14) years; % female: 56 %, 73 %; race: 69 % White, 97 % Mestizo. Stage II: N = 34 adults (12 US, 22 Mexico); age: 37 (14), 39 (11) years; % female: 50 %, 50 %; race: 58 % White, 100 % Mestizo. Symptoms: Symptoms identified by >50 %: coughing, weak or tired, throat symptoms, congestion, headache, weakness, sweating, chills, general discomfort, runny nose, chest (trouble breathing), difficulty sleeping, and body aches or pains. No new content was uncovered during Stage II; participants easily understood the instrument. Conclusions: Results show the 37-item Flu-PRO is a content valid measure of influenza symptoms in adults with a confirmed diagnosis of influenza. Research is underway to evaluate the suitability of the instrument for children and adolescents. This work can form the basis for future quantitative tests of reliability, validity, and responsiveness to evaluate the measurement properties of Flu-PRO for use in clinical trials and epidemiology studies. C1 [Powers, John H.; Rosenberg, Alice] Leidos Biomed Res Inc, Clin Monitoring & Res Program, Clin Res Directorate, Frederick Natl Lab Canc Res, Frederick, MD 21702 USA. [Powers, John H.; Rosenberg, Alice] NIAID, Collaborat Clin Res Branch, Div Clin Res, Bethesda, MD 20892 USA. [Guerrero, M. Lourdes; Ortega-Gallegos, Hilda; Galindo-Fraga, Arturo; Ruiz-Palacios, Guillermo M.] Inst Nacl Ciencias Med & Nutr Salvador Zubiran, Mexico City, DF, Mexico. [Leidy, Nancy Kline; Stringer, Sonja; Kim, Katherine; Bacci, Elizabeth Dansie] Evidera, Bethesda, MD USA. [Fairchok, Mary P.; Ridore, Michelande; Millar, Eugene V.] Uniformed Serv Univ Hlth Sci, Infect Dis Clin Res Program, Bethesda, MD 20814 USA. [Fairchok, Mary P.; Ridore, Michelande; Millar, Eugene V.] Henry M Jackson Fdn Adv Mil Med, Bethesda, MD USA. [Fairchok, Mary P.; Schofield, Christina] Madigan Army Med Ctr, Tacoma, WA 98431 USA. [Hernandez, Andres] Inst Nacl Enfermedades Infecciosas, Mexico City, DF, Mexico. [Rodriguez-Zulueta, Patricia] Hosp Gen Dr Manuel Gea Gonzalez, Mexico City, DF, Mexico. [Danaher, Patrick J.] San Antonio Hlth Syst, San Antonio, TX USA. [Stepp, Nathaniel] Camp Lejeune, Jacksonville, NC USA. [St Clair, Kristina] Naval Med Ctr Portsmouth, Portsmouth, VA USA. [Rajnik, Michael] Walter Reed Natl Mil Med Ctr, Bethesda, MD USA. [McDonough, Erin A.] Naval Hlth Res Ctr, San Diego, CA USA. [Arnold, John C.] Naval Med Ctr San Diego, San Diego, CA USA. RP Powers, JH (reprint author), Leidos Biomed Res Inc, Clin Monitoring & Res Program, Clin Res Directorate, Frederick Natl Lab Canc Res, Frederick, MD 21702 USA. EM john.powers@nih.gov FU National Cancer Institute, National Institutes of Health [HHSN261200800001E]; National Institutes of Allergy and Infectious Diseases FX This project has been funded in whole or in part with federal funds from the National Cancer Institute, National Institutes of Health, under Contract No. HHSN261200800001E. The content of this publication does not necessarily reflect the views or policies of the Department of Health and Human Services, nor does mention of trade names, commercial products, or organizations imply endorsement by the U.S. Government. This project was supported by the National Institutes of Allergy and Infectious Diseases. NR 13 TC 3 Z9 3 U1 2 U2 6 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1471-2334 J9 BMC INFECT DIS JI BMC Infect. Dis. PD JAN 5 PY 2016 VL 16 AR 1 DI 10.1186/s12879-015-1330-0 PG 11 WC Infectious Diseases SC Infectious Diseases GA DA1PC UT WOS:000367566700001 PM 26729246 ER PT J AU Sun, J Li, N Oh, KS Dutta, B Vayttaden, SJ Lin, B Ebert, TS De Nardo, D Davis, J Bagirzadeh, R Lounsbury, NW Pasare, C Latz, E Hornung, V Fraser, IDC AF Sun, Jing Li, Ning Oh, Kyu-Seon Dutta, Bhaskar Vayttaden, Sharat J. Lin, Bin Ebert, Thomas S. De Nardo, Dominic Davis, Joie Bagirzadeh, Rustam Lounsbury, Nicolas W. Pasare, Chandrashekhar Latz, Eicke Hornung, Veit Fraser, Iain D. C. TI Comprehensive RNAi-based screening of human and mouse TLR pathways identifies species-specific preferences in signaling protein use SO SCIENCE SIGNALING LA English DT Article ID SYSTEMIC-LUPUS-ERYTHEMATOSUS; NF-KAPPA-B; DOUBLE-STRANDED-RNA; INTERLEUKIN-1 RECEPTOR; KINASE-ACTIVITY; INNATE IMMUNITY; RHEUMATOID-ARTHRITIS; BACTERIAL-INFECTIONS; PATHOGEN RECOGNITION; NLRP3 INFLAMMASOME AB Toll-like receptors (TLRs) are a major class of pattern recognition receptors, whichmediate the responses of innate immune cells to microbial stimuli. To systematically determine the roles of proteins in canonical TLR signaling pathways, we conducted an RNA interference (RNAi)-based screen in human and mouse macrophages. We observed a pattern of conserved signaling module dependencies across species, but found notable species-specific requirements at the level of individual proteins. Among these, weidentified unexpected differences in the involvement of members of the interleukin-1 receptor-associated kinase (IRAK) family between the human andmouse TLR pathways. Whereas TLR signaling inmousemacrophages depended primarily on IRAK4 and IRAK2, with little or no role for IRAK1, TLR signaling and proinflammatory cytokine production in human macrophages depended on IRAK1, with knockdown of IRAK4 or IRAK2 having less of an effect. Consistent with species-specific roles for these kinases, IRAK4 orthologs failed to rescue signaling in IRAK4-deficient macrophages from the other species, and only mouse macrophages required the kinase activity of IRAK4 to mediate TLR responses. The identification of a critical role for IRAK1 in TLR signaling in humans could potentially explain the association of IRAK1 with several autoimmune diseases. Furthermore, this study demonstrated how systematic screening can be used to identify important characteristics of innate immune responses across species, which could optimize therapeutic targeting to manipulate human TLR-dependent outputs. C1 [Sun, Jing; Li, Ning; Oh, Kyu-Seon; Vayttaden, Sharat J.; Lin, Bin; Lounsbury, Nicolas W.; Fraser, Iain D. C.] NIAID, Signaling Syst Unit, Lab Syst Biol, NIH, Bethesda, MD 20892 USA. [Dutta, Bhaskar] NIAID, Bioinformat Team, Lab Syst Biol, NIH, Bethesda, MD 20892 USA. [Ebert, Thomas S.; Hornung, Veit] Univ Bonn, Univ Hosp, Inst Mol Med, D-53127 Bonn, Germany. [De Nardo, Dominic; Latz, Eicke] Univ Bonn, Univ Hosp, Biomed Ctr, Inst Innate Immun, D-53127 Bonn, Germany. [De Nardo, Dominic] Walter & Eliza Hall Inst Med Res, Inflammat Div, Parkville, Vic 3052, Australia. [De Nardo, Dominic] Univ Melbourne, Dept Med Biol, Parkville, Vic 3010, Australia. [Davis, Joie] NIAID, Lab Clin Infect Dis, NIH, Bethesda, MD 20892 USA. [Bagirzadeh, Rustam; Pasare, Chandrashekhar] Univ Texas SW Med Ctr Dallas, Dept Immunol, Dallas, TX 75390 USA. [Latz, Eicke] German Ctr Neurodegenerat Dis DZNE, D-53175 Bonn, Germany. [Latz, Eicke] Univ Massachusetts, Sch Med, Dept Infect Dis & Immunol, Worcester, MA 01605 USA. RP Fraser, IDC (reprint author), NIAID, Signaling Syst Unit, Lab Syst Biol, NIH, Bethesda, MD 20892 USA. EM fraseri@niaid.nih.gov OI De Nardo, Dominic/0000-0002-7045-4695 FU National Institute of Allergy and Infectious Diseases (NIAID); BONFOR research commission at the University of Bonn; German Research Foundation [SFB704, SFB670]; European Research Council [ERC-2009-StG 243046]; NIH [R01HL112661]; Deutsche Forschungsgemeinschaft [SFB670]; European Research Council (ERC InflammAct); NIAID [AI082265]; Welch Foundation [I-1820]; NIH Integrative Immunology Training program grant [5T32-AI005284-35] FX This work was supported by the Intramural Research Program of the National Institute of Allergy and Infectious Diseases (NIAID) (to J. S., N. L., K.-S. O., B. D., S. J. V., B. L., J. D., N. W. L., and I. D. C. F.) and the BONFOR research commission at the University of Bonn (to D. D. N.). V. H. and T. S. E. are supported by grants from the German Research Foundation (SFB704 and SFB670) and the European Research Council (ERC-2009-StG 243046). E. L. is supported by grants from the NIH (R01HL112661), the Deutsche Forschungsgemeinschaft (SFB670), and the European Research Council (ERC InflammAct). E. L. and V. H. are members of the ImmunoSensation cluster of excellence. C. P. is supported by grants from the NIAID (AI082265) and The Welch Foundation (I-1820). R. B. is supported by an NIH Integrative Immunology Training program grant (5T32-AI005284-35). NR 63 TC 9 Z9 9 U1 1 U2 14 PU AMER ASSOC ADVANCEMENT SCIENCE PI WASHINGTON PA 1200 NEW YORK AVE, NW, WASHINGTON, DC 20005 USA SN 1945-0877 EI 1937-9145 J9 SCI SIGNAL JI Sci. Signal. PD JAN 5 PY 2016 VL 9 IS 409 AR ra3 PG 17 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA DA3BX UT WOS:000367672000004 PM 26732763 ER PT J AU Weitzel, KW Alexander, M Bernhardt, BA Calman, N Carey, DJ Cavallari, LH Field, JR Hauser, D Junkins, HA Levin, PA Levy, K Madden, EB Manolio, TA Odgis, J Orlando, LA Pyeritz, R Wu, RR Shuldiner, AR Bottinger, EP Denny, JC Dexter, PR Flockhart, DA Horowitz, CR Johnson, JA Kimmel, SE Levy, MA Pollin, TI Ginsburg, GS AF Weitzel, Kristin Wiisanen Alexander, Madeline Bernhardt, Barbara A. Calman, Neil Carey, David J. Cavallari, Larisa H. Field, Julie R. Hauser, Diane Junkins, Heather A. Levin, Phillip A. Levy, Kenneth Madden, Ebony B. Manolio, Teri A. Odgis, Jacqueline Orlando, Lori A. Pyeritz, Reed Wu, R. Ryanne Shuldiner, Alan R. Bottinger, Erwin P. Denny, Joshua C. Dexter, Paul R. Flockhart, David A. Horowitz, Carol R. Johnson, Julie A. Kimmel, Stephen E. Levy, Mia A. Pollin, Toni I. Ginsburg, Geoffrey S. CA IGNITE Network TI The IGNITE network: a model for genomic medicine implementation and research SO BMC MEDICAL GENOMICS LA English DT Article DE Precision medicine; Pharmacogenomics; Genomics; Personalized medicine; Clinical decision support; Electronic health record; Implementation ID RISK-ASSESSMENT; CONSORTIUM; HISTORY; CANCER; CARE AB Background: Patients, clinicians, researchers and payers are seeking to understand the value of using genomic information (as reflected by genotyping, sequencing, family history or other data) to inform clinical decision-making. However, challenges exist to widespread clinical implementation of genomic medicine, a prerequisite for developing evidence of its real-world utility. Methods: To address these challenges, the National Institutes of Health-funded IGNITE (Implementing GeNomics In pracTicE; www.ignite-genomics.org) Network, comprised of six projects and a coordinating center, was established in 2013 to support the development, investigation and dissemination of genomic medicine practice models that seamlessly integrate genomic data into the electronic health record and that deploy tools for point of care decision making. IGNITE site projects are aligned in their purpose of testing these models, but individual projects vary in scope and design, including exploring genetic markers for disease risk prediction and prevention, developing tools for using family history data, incorporating pharmacogenomic data into clinical care, refining disease diagnosis using sequence-based mutation discovery, and creating novel educational approaches. Results: This paper describes the IGNITE Network and member projects, including network structure, collaborative initiatives, clinical decision support strategies, methods for return of genomic test results, and educational initiatives for patients and providers. Clinical and outcomes data from individual sites and network-wide projects are anticipated to begin being published over the next few years. Conclusions: The IGNITE Network is an innovative series of projects and pilot demonstrations aiming to enhance translation of validated actionable genomic information into clinical settings and develop and use measures of outcome in response to genome-based clinical interventions using a pragmatic framework to provide early data and proofs of concept on the utility of these interventions. Through these efforts and collaboration with other stakeholders, IGNITE is poised to have a significant impact on the acceleration of genomic information into medical practice. C1 [Weitzel, Kristin Wiisanen; Cavallari, Larisa H.; Johnson, Julie A.] Univ Florida, Coll Pharm, Dept Pharmacotherapy & Translat Res, Gainesville, FL USA. [Weitzel, Kristin Wiisanen; Cavallari, Larisa H.; Johnson, Julie A.] Univ Florida, Coll Pharm, Ctr Pharmacogen, Gainesville, FL USA. [Alexander, Madeline; Kimmel, Stephen E.] Univ Penn, Perelman Sch Med, Ctr Therapeut Effectiveness Res, Philadelphia, PA 19104 USA. [Bernhardt, Barbara A.; Pyeritz, Reed] Univ Penn, Perelman Sch Med, Div Translat Med & Human Genet, Philadelphia, PA 19104 USA. [Calman, Neil; Hauser, Diane] Inst Family Hlth, New York, NY USA. [Carey, David J.] Geisinger Hlth Syst, Weis Ctr Res, Danville, PA USA. [Field, Julie R.] Vanderbilt Univ, Sch Med, Inst Clin & Translat Res, Nashville, TN 37235 USA. [Junkins, Heather A.; Madden, Ebony B.; Manolio, Teri A.; Odgis, Jacqueline] NHGRI, NIH, Div Genom Med, Bethesda, MD 20892 USA. [Levin, Phillip A.] Bay West Endocrinol Associates & MODEL Clin Res, Baltimore, MD USA. [Levy, Kenneth; Dexter, Paul R.; Flockhart, David A.] Indiana Univ, Sch Med, Dept Med, Bloomington, IN 47405 USA. [Orlando, Lori A.; Wu, R. Ryanne] Duke Univ, Med Ctr, Div Gen Internal Med, Durham, NC 27710 USA. [Shuldiner, Alan R.; Pollin, Toni I.] Univ Maryland, Sch Med, Baltimore, MD 21201 USA. [Shuldiner, Alan R.] Regeneron Pharmaceut Inc, Tarrytown, NY USA. [Bottinger, Erwin P.] Icahn Sch Med Mt Sinai, Charles Bronfman Inst Personalized Med, New York, NY 10029 USA. [Denny, Joshua C.] Vanderbilt Univ, Sch Med, Dept Biomed Informat, Nashville, TN 37235 USA. [Denny, Joshua C.] Vanderbilt Univ, Sch Med, Dept Med, Nashville, TN 37235 USA. [Denny, Joshua C.] Vanderbilt Univ, Sch Med, Dept Med, Div Gen Internal Med, Nashville, TN 37235 USA. [Horowitz, Carol R.] Icahn Sch Med Mt Sinai, Dept Populat Hlth Sci & Policy, New York, NY 10029 USA. [Kimmel, Stephen E.] Univ Penn, Perelman Sch Med, Ctr Clin Epidemiol & Biostat, Ctr Therapeut Effectiveness Res, Philadelphia, PA 19104 USA. [Levy, Mia A.] Vanderbilt Univ, Sch Med, Div Hematol & Oncol, Dept Biomed Informat, Nashville, TN 37235 USA. [Orlando, Lori A.; Wu, R. Ryanne; Ginsburg, Geoffrey S.] Duke Univ, Med Ctr, Duke Ctr Appl Genom & Precis Med, Durham, NC 27708 USA. EM geoffrey.ginsburg@DM.DUKE.EDU FU National Institutes of Health [U01 HG007269, UL1 TR 000064, U01 HG007253, U01 HG007762, U01 HG007282, U01 HG007775, U01 HG007266, U01 HG007278] FX This work was supported by grants from the National Institutes of Health (U01 HG007269 [J.A.J.], UL1 TR 000064 [J.A.J.], U01 HG007253 [J.C.D., M.A.L.], U01 HG007762 [D.A.F., P.R.D.], U01 HG007282 [G.S.G.], U01 HG007775 [T.I.P.], U01 HG007266 [S.E.K.], U01 HG007278 [E.P.B, C.R.H.]. NR 16 TC 17 Z9 18 U1 2 U2 12 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1755-8794 J9 BMC MED GENOMICS JI BMC Med. Genomics PD JAN 5 PY 2016 VL 9 AR 1 DI 10.1186/s12920-015-0162-5 PG 13 WC Genetics & Heredity SC Genetics & Heredity GA DA1QI UT WOS:000367570000001 PM 26729011 ER PT J AU Van Driest, SL Wells, QS Stallings, S Bush, WS Gordon, A Nickerson, DA Kim, JH Crosslin, DR Jarvik, GP Carrell, DS Ralston, JD Larson, EB Bielinski, SJ Olson, JE Ye, Z Kullo, IJ Abul-Husn, NS Scott, SA Bottinger, E Almoguera, B Connolly, J Chiavacci, R Hakonarson, H Rasmussen-Torvik, LJ Pan, V Persell, SD Smith, M Chisholm, RL Kitchner, TE He, MM Brilliant, MH Wallace, JR Doheny, KF Shoemaker, B Li, RL Manolio, TA Callis, TE Macaya, D Williams, MS Carey, D Kapplinger, JD Ackerman, MJ Ritchie, MD Denny, JC Roden, DM AF Van Driest, Sara L. Wells, Quinn S. Stallings, Sarah Bush, William S. Gordon, Adam Nickerson, Deborah A. Kim, Jerry H. Crosslin, David R. Jarvik, Gail P. Carrell, David S. Ralston, James D. Larson, Eric B. Bielinski, Suzette J. Olson, Janet E. Ye, Zi Kullo, Iftikhar J. Abul-Husn, Noura S. Scott, Stuart A. Bottinger, Erwin Almoguera, Berta Connolly, John Chiavacci, Rosetta Hakonarson, Hakon Rasmussen-Torvik, Laura J. Pan, Vivian Persell, Stephen D. Smith, Maureen Chisholm, Rex L. Kitchner, Terrie E. He, Max M. Brilliant, Murray H. Wallace, John R. Doheny, Kimberly F. Shoemaker, Benjamin Li, Rongling Manolio, Teri A. Callis, Thomas E. Macaya, Daniela Williams, Marc S. Carey, David Kapplinger, Jamie D. Ackerman, Michael J. Ritchie, Marylyn D. Denny, Joshua C. Roden, Dan M. TI Association of Arrhythmia-Related Genetic Variants With Phenotypes Documented in Electronic Medical Records SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Article ID LONG-QT SYNDROME; CARDIAC SODIUM-CHANNEL; INCIDENTAL FINDINGS; SEQUENCE VARIANTS; EMERGE NETWORK; PREVALENCE; GENOMICS; RETURN; SCN5A; SUSCEPTIBILITY AB IMPORTANCE Large-scale DNA sequencing identifies incidental rare variants in established Mendelian disease genes, but the frequency of related clinical phenotypes in unselected patient populations is not well established. Phenotype data from electronic medical records (EMRs) may provide a resource to assess the clinical relevance of rare variants. OBJECTIVE To determine the clinical phenotypes from EMRs for individuals with variants designated as pathogenic by expert review in arrhythmia susceptibility genes. DESIGN, SETTING, AND PARTICIPANTS This prospective cohort study included 2022 individuals recruited for nonantiarrhythmic drug exposure phenotypes from October 5, 2012, to September 30, 2013, for the Electronic Medical Records and Genomics Network Pharmacogenomics project from 7 US academic medical centers. Variants in SCN5A and KCNH2, disease genes for long QT and Brugada syndromes, were assessed for potential pathogenicity by 3 laboratories with ion channel expertise and by comparison with the ClinVar database. Relevant phenotypes were determined from EMRs, with data available from 2002 (or earlier for some sites) through September 10, 2014. EXPOSURES One or more variants designated as pathogenic in SCN5A or KCNH2. MAIN OUTCOMES AND MEASURES Arrhythmia or electrocardiographic (ECG) phenotypes defined by International Classification of Diseases, Ninth Revision (ICD-9) codes, ECG data, and manual EMR review. RESULTS Among 2022 study participants (median age, 61 years [interquartile range, 56-65 years]; 1118 [55%] female; 1491 [74%] white), a total of 122 rare (minor allele frequency < 0.5%) nonsynonymous and splice-site variants in 2 arrhythmia susceptibility genes were identified in 223 individuals (11% of the study cohort). Forty-two variants in 63 participants were designated potentially pathogenic by at least 1 laboratory or ClinVar, with low concordance across laboratories (Cohen k = 0.26). An ICD-9 code for arrhythmia was found in 11 of 63 (17%) variant carriers vs 264 of 1959 (13%) of those without variants (difference, +4%; 95% CI, -5% to +13%; P = .35). In the 1270 (63%) with ECGs, corrected QT intervals were not different in variant carriers vs those without (median, 429 vs 439 milliseconds; difference, -10 milliseconds; 95% CI, -16 to +3 milliseconds; P = .17). After manual review, 22 of 63 participants (35%) with designated variants had any ECG or arrhythmia phenotype, and only 2 had corrected QT interval longer than 500 milliseconds. CONCLUSIONS AND RELEVANCE Among laboratories experienced in genetic testing for cardiac arrhythmia disorders, there was low concordance in designating SCN5A and KCNH2 variants as pathogenic. In an unselected population, the putatively pathogenic genetic variants were not associated with an abnormal phenotype. These findings raise questions about the implications of notifying patients of incidental genetic findings. C1 [Van Driest, Sara L.; Wells, Quinn S.; Stallings, Sarah; Bush, William S.; Shoemaker, Benjamin; Denny, Joshua C.; Roden, Dan M.] Vanderbilt Univ, Med Ctr, Nashville, TN 37232 USA. [Bush, William S.] Case Western Reserve Univ, Cleveland, OH 44106 USA. [Gordon, Adam; Nickerson, Deborah A.; Kim, Jerry H.; Crosslin, David R.; Jarvik, Gail P.] Univ Washington, Seattle, WA 98195 USA. [Carrell, David S.; Ralston, James D.; Larson, Eric B.] Grp Hlth Res Inst, Seattle, WA USA. [Bielinski, Suzette J.; Olson, Janet E.; Ye, Zi; Kullo, Iftikhar J.; Kapplinger, Jamie D.; Ackerman, Michael J.] Mayo Clin, Rochester, MN USA. [Abul-Husn, Noura S.; Scott, Stuart A.; Bottinger, Erwin] Icahn Sch Med Mt Sinai, New York, NY 10029 USA. [Almoguera, Berta; Connolly, John; Chiavacci, Rosetta; Hakonarson, Hakon] Childrens Hosp Philadelphia, Philadelphia, PA 19104 USA. [Hakonarson, Hakon] Univ Penn, Perelman Sch Med, Philadelphia, PA 19104 USA. [Rasmussen-Torvik, Laura J.; Pan, Vivian; Persell, Stephen D.; Smith, Maureen; Chisholm, Rex L.] Northwestern Univ, Feinberg Sch Med, Chicago, IL 60611 USA. [Kitchner, Terrie E.; He, Max M.; Brilliant, Murray H.] Marshfield Clin Res Fdn, Marshfield, WI USA. [Wallace, John R.; Ritchie, Marylyn D.] Penn State Univ, University Pk, PA 16802 USA. [Doheny, Kimberly F.] Johns Hopkins Sch Med, Baltimore, MD USA. [Li, Rongling; Manolio, Teri A.] NHGRI, NIH, Bethesda, MD 20892 USA. [Callis, Thomas E.] Transgenomic, New Haven, CT USA. [Macaya, Daniela] GeneDx, Gaithersburg, MD USA. [Williams, Marc S.; Carey, David; Ritchie, Marylyn D.] Geisinger Hlth Syst, Danville, PA USA. RP Roden, DM (reprint author), Vanderbilt Univ, Med Ctr, 2215B Garland Ave,Room 1285, Nashville, TN 37232 USA. EM dan.roden@vanderbilt.edu RI Bielinski, Suzette/A-2238-2009; OI Bielinski, Suzette/0000-0002-2905-5430; Bush, William/0000-0002-9729-6519 FU National Human Genome Research Institute (NHGRI) [U01HG006828, U01HG006830, U01HG006389, U01HG006382, U01HG006375, U01HG006379, U01HG006380, U01HG006388, U01HG006378, U01HG006385]; National Center for Advancing Translational Sciences (NCATS) [UL1TR000427]; National Institute on Aging [U01AG006781]; NHGRI [U01HG004438]; NCATS [UL1TR000445]; National Institute of General Medical Sciences grants [U19GM61388, R01GM28157, U01HG005137, R01CA138461, R01AG034676]; Windland Smith Rice Comprehensive Sudden Cardiac Death Program (Mayo Clinic); National Institutes of Health [U19GM61388, U19HL069757, U01GM097119] FX The eMERGE Network was initiated and funded by the National Human Genome Research Institute (NHGRI) through the following grants: U01HG006828 (Cincinnati Children's Hospital Medical Center/Boston Children's Hospital); U01HG006830 (Children's Hospital of Philadelphia); U01HG006389 (Essentia Institute of Rural Health, Marshfield Clinic Research Foundation, and Pennsylvania State University); U01HG006382 (Geisinger Clinic); U01HG006375 (Group Health Cooperative, University of Washington); U01HG006379 (Mayo Clinic); U01HG006380 (Icahn School of Medicine at Mount Sinai); U01HG006388 (Northwestern University); U01HG006378 (Vanderbilt University Medical Center); and U01HG006385 (Vanderbilt University Medical Center serving as the Coordinating Center). Additional support was provided by National Center for Advancing Translational Sciences (NCATS) grant UL1TR000427 (University of Wisconsin, Marshfield Clinic); National Institute on Aging grant U01AG006781 (Group Health Cooperative, University of Washington); NHGRI grant U01HG004438 (Johns Hopkins School of Medicine); NCATS grant UL1TR000445 (Vanderbilt University Medical Center); National Institute of General Medical Sciences grants U19GM61388, R01GM28157, U01HG005137, R01CA138461, R01AG034676; and the Windland Smith Rice Comprehensive Sudden Cardiac Death Program (Mayo Clinic). The sequencing platform was developed by the next-generation sequencing centers of the Pharmacogenomics Research Network supported by National Institutes of Health grants U19GM61388, U19HL069757, and U01GM097119. NR 35 TC 29 Z9 29 U1 1 U2 11 PU AMER MEDICAL ASSOC PI CHICAGO PA 330 N WABASH AVE, STE 39300, CHICAGO, IL 60611-5885 USA SN 0098-7484 EI 1538-3598 J9 JAMA-J AM MED ASSOC JI JAMA-J. Am. Med. Assoc. PD JAN 5 PY 2016 VL 315 IS 1 BP 47 EP 57 DI 10.1001/jama.2015.17701 PG 11 WC Medicine, General & Internal SC General & Internal Medicine GA DA0YH UT WOS:000367523000014 PM 26746457 ER PT J AU Agarwala, R Barrett, T Beck, J Benson, DA Bollin, C Bolton, E Bourexis, D Brister, JR Bryant, SH Lanese, K Charowhas, C Clark, K DiCuccio, M Dondoshansky, I Federhen, S Feolo, M Funk, K Geer, LY Gorelenkov, V Hoeppner, M Holmes, B Johnson, M Khotomlianski, V Kimchi, A Kimelman, M Kitts, P Klimke, W Krasnov, S Kuznetsov, A Landrum, MJ Landsman, D Lee, JM Lipman, DJ Lu, ZY Madden, TL Madcj, T Marchler-Bauer, A Karsch-Mizrachi, I Murphy, T Orris, R Ostell, J O'Sullivan, C Panchenko, A Phan, L Preuss, D Pruitt, KD Rodarmer, K Rubinstein, W Sayers, EW Schneider, V Schuler, GD Sherry, ST Sirotkin, K Siyan, K Slotta, D Soboleva, A Soussov, V Starchenko, G Tatusova, TA Todorov, K Trawick, BW Vakatov, D Wang, YL Ward, M Wilbur, WJ Yaschenko, E Zbicz, K AF Agarwala, Richa Barrett, Tanya Beck, Jeff Benson, Dennis A. Bollin, Colleen Bolton, Evan Bourexis, Devon Brister, J. Rodney Bryant, Stephen H. Lanese, Kathi Charowhas, Chad Clark, Karen DiCuccio, Michael Dondoshansky, Ilya Federhen, Scott Feolo, Michael Funk, Kathryn Geer, Lewis Y. Gorelenkov, Viatcheslav Hoeppner, Marilu Holmes, Brad Johnson, Mark Khotomlianski, Viatcheslav Kimchi, Avi Kimelman, Michael Kitts, Paul Klimke, William Krasnov, Sergey Kuznetsov, Anatoliy Landrum, Melissa J. Landsman, David Lee, Jennifer M. Lipman, David J. Lu, Zhiyong Madden, Thomas L. Madcj, Torn Marchler-Bauer, Aron Karsch-Mizrachi, Ilene Murphy, Terence Orris, Rebecca Ostell, James O'Sullivan, Christopher Panchenko, Anna Lon Phan Preuss, Don Pruitt, Kim D. Rodarmer, Kurt Rubinstein, Wendy Sayers, Eric W. Schneider, Valerie Schuler, Gregory D. Sherry, Stephen T. Sirotkin, Karl Siyan, Kara Slotta, Douglas Soboleva, Alexandra Soussov, Vladimir Starchenko, Grigory Tatusova, Tatiana A. Todorov, Kamen Trawick, Bart W. Vakatov, Denis Wang, Yanli Ward, Minghong Wilbur, W. John Yaschenko, Eugene Zbicz, Kerry CA NCBI Resource Coordinators TI Database resources of the National Center for Biotechnology Information SO NUCLEIC ACIDS RESEARCH LA English DT Article ID CONSERVED DOMAIN DATABASE; NCBI TAXONOMY DATABASE; BIOLOGICAL PATHWAYS; GENE ONTOLOGY; SEQUENCE; GENOMES; TOOL; ARCHIVE; VIRUS; ANNOTATION AB The National Center for Biotechnology Information (NCBI) provides a large suite of online resources for biological information and data, including the GenBank (R) nucleic acid sequence database and the PubMed database of citations and abstracts for published life science journals. Additional NCBI resources focus on literature (PubMed Central (PMC), Bookshelf and PubReader), health (ClinVar, dbGaP, dbMHC, the Genetic Testing Registry, HIV-1/Human Protein Interaction Database and MedGen), genomes (BioProject, Assembly, Genome, BioSample, dbSNP, dbVar, Epigenomics, the Map Viewer, Nucleotide, Probe, RefSeq, Sequence Read Archive, the Taxonomy Browser and the Trace Archive), genes (Gene, Gene Expression Omnibus (GEO), HomoloGene, PopSet and UniGene), proteins (Protein, the Conserved Domain Database (CDD), COBALT, Conserved Domain Architecture Retrieval Tool (CDART), the Molecular Modeling Database (MMDB) and Protein Clusters) and chemicals (Biosystems and the PubChem suite of small molecule databases). The Entrez system provides search and retrieval operations for most of these databases. Augmenting many of the web applications are custom implementations of the BLAST program optimized to search specialized datasets. All of these resources can be accessed through the NCBI home page at www.ncbi.nlm.nih.gov. C1 [Agarwala, Richa; Barrett, Tanya; Beck, Jeff; Benson, Dennis A.; Bollin, Colleen; Bolton, Evan; Bourexis, Devon; Brister, J. Rodney; Bryant, Stephen H.; Lanese, Kathi; Charowhas, Chad; Clark, Karen; DiCuccio, Michael; Dondoshansky, Ilya; Federhen, Scott; Feolo, Michael; Funk, Kathryn; Geer, Lewis Y.; Gorelenkov, Viatcheslav; Hoeppner, Marilu; Holmes, Brad; Johnson, Mark; Khotomlianski, Viatcheslav; Kimchi, Avi; Kimelman, Michael; Kitts, Paul; Klimke, William; Krasnov, Sergey; Kuznetsov, Anatoliy; Landrum, Melissa J.; Landsman, David; Lee, Jennifer M.; Lipman, David J.; Lu, Zhiyong; Madden, Thomas L.; Madcj, Torn; Marchler-Bauer, Aron; Karsch-Mizrachi, Ilene; Murphy, Terence; Orris, Rebecca; Ostell, James; O'Sullivan, Christopher; Panchenko, Anna; Lon Phan; Preuss, Don; Pruitt, Kim D.; Rodarmer, Kurt; Rubinstein, Wendy; Sayers, Eric W.; Schneider, Valerie; Schuler, Gregory D.; Sherry, Stephen T.; Sirotkin, Karl; Siyan, Kara; Slotta, Douglas; Soboleva, Alexandra; Soussov, Vladimir; Starchenko, Grigory; Tatusova, Tatiana A.; Todorov, Kamen; Trawick, Bart W.; Vakatov, Denis; Wang, Yanli; Ward, Minghong; Wilbur, W. John; Yaschenko, Eugene; Zbicz, Kerry; NCBI Resource Coordinators] NIH, Natl Ctr Biotechnol Informat, Natl Lib Med, Bldg 38A,8600 Rockville Pike, Bethesda, MD 20894 USA. RP Sayers, EW (reprint author), NIH, Natl Ctr Biotechnol Informat, Natl Lib Med, Bldg 38A,8600 Rockville Pike, Bethesda, MD 20894 USA. EM sayers@ncbi.nlm.nih.gov OI Landsman, David/0000-0002-9819-6675 FU National Institutes of Health, National Library of Medicine FX Funding for open access charge: Intramural Research Program of the National Institutes of Health, National Library of Medicine. NR 69 TC 21 Z9 21 U1 16 U2 37 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0305-1048 EI 1362-4962 J9 NUCLEIC ACIDS RES JI Nucleic Acids Res. PD JAN 4 PY 2016 VL 44 IS D1 BP D7 EP D19 DI 10.1093/nar/gkv1290 PG 13 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA DF3QY UT WOS:000371261700002 ER PT J AU Clark, K Karsch-Mizrachi, I Lipman, DJ Ostell, J Sayers, EW AF Clark, Karen Karsch-Mizrachi, Ilene Lipman, David J. Ostell, James Sayers, Eric W. TI GenBank SO NUCLEIC ACIDS RESEARCH LA English DT Article ID DATABASE; ANNOTATION; ARCHIVE AB GenBank (R) (www.ncbi.nlm.nih.gov/genbank/) is a comprehensive database that contains publicly available nucleotide sequences for over 340 000 formally described species. Recent developments include a new starting page for submitters, a shift toward using accession. version identifiers rather than GI numbers, a wizard for submitting 16S rRNA sequences, and an Identical Protein Report to address growing issues of data redundancy. GenBank organizes the sequence data received from individual laboratories and largescale sequencing projects into 18 divisions, and GenBank staff assign unique accession. version identifiers upon data receipt. Most submitters use the web-based BankIt or standalone Sequin programs. Daily data exchange with the European Nucleotide Archive (ENA) and the DNA Data Bank of Japan (DDBJ) ensures worldwide coverage. GenBank is accessible through the nuccore, nucest, and nucgss databases of the Entrez retrieval system, which integrates these records with a variety of other data including taxonomy nodes, genomes, protein structures, and biomedical journal literature in PubMed. BLAST provides sequence similarity searches of GenBank and other sequence databases. Complete bimonthly releases and daily updates of the GenBank database are available by FTP. C1 [Clark, Karen; Karsch-Mizrachi, Ilene; Lipman, David J.; Ostell, James; Sayers, Eric W.] NIH, Natl Ctr Biotechnol Informat, Natl Lib Med, Bldg 38A,8600 Rockville Pike, Bethesda, MD 20894 USA. RP Sayers, EW (reprint author), NIH, Natl Ctr Biotechnol Informat, Natl Lib Med, Bldg 38A,8600 Rockville Pike, Bethesda, MD 20894 USA. EM sayers@ncbi.nlm.nih.gov FU National Institutes of Health, National Library of Medicine FX Funding for open access charge: Intramural Research Program of the National Institutes of Health, National Library of Medicine. NR 14 TC 32 Z9 32 U1 4 U2 22 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0305-1048 EI 1362-4962 J9 NUCLEIC ACIDS RES JI Nucleic Acids Res. PD JAN 4 PY 2016 VL 44 IS D1 BP D67 EP D72 DI 10.1093/nar/gkv1276 PG 6 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA DF3QY UT WOS:000371261700009 PM 26590407 ER PT J AU Cochrane, G Karsch-Mizrachi, I Takagi, T AF Cochrane, Guy Karsch-Mizrachi, Ilene Takagi, Toshihisa CA Int Nucleotide Sequence Database TI The International Nucleotide Sequence Database Collaboration SO NUCLEIC ACIDS RESEARCH LA English DT Article AB The International Nucleotide Sequence Database Collaboration (INSDC;http://www.insdc.org) comprises three global partners committed to capturing, preserving and providing comprehensive publicdomain nucleotide sequence information. The INSDC establishes standards, formats and protocols for data and metadata to make it easier for individuals and organisations to submit their nucleotide data reliably to public archives. This work enables the continuous, global exchange of information about living things. Here we present an update of the INSDC in 2015, including data growth and diversification, new standards and requirements by publishers for authors to submit their data to the public archives. The INSDC serves as a model for data sharing in the life sciences. C1 [Cochrane, Guy] European Bioinformat Inst EMBL EBI, European Mol Biol Lab, Wellcome Genome Campus, Cambridge CB10 1SD, England. [Karsch-Mizrachi, Ilene] NIH, Natl Ctr Biotechnol Informat, Natl Lib Med, Bethesda, MD 20894 USA. [Takagi, Toshihisa] Natl Inst Genet, DDBJ Ctr, Mishima, Shizuoka 411, Japan. RP Cochrane, G (reprint author), European Bioinformat Inst EMBL EBI, European Mol Biol Lab, Wellcome Genome Campus, Cambridge CB10 1SD, England. EM cochrane@ebi.ac.uk OI Cochrane, Guy/0000-0001-7954-7057 FU Ministry of Education, Culture, Sports, Science and Technology of Japan (MEXT); European Molecular Biology Laboratory; Wellcome Trust; European Commission; Biotechnology, Biological Sciences Research Council; Oxford Nanopore Technologies; NIH, National Library of Medicine; EMBL FX Ministry of Education, Culture, Sports, Science and Technology of Japan (MEXT) (to DDBJ); the European Nucleotide Archive is funded by the European Molecular Biology Laboratory; Wellcome Trust; European Commission FP7 and Horizon 2020 Programmes; Biotechnology, Biological Sciences Research Council and Oxford Nanopore Technologies; This research was supported in part by the Intramural Research Program of the NIH, National Library of Medicine (to NCBI). Funding for open access charge: EMBL. NR 5 TC 12 Z9 12 U1 0 U2 0 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0305-1048 EI 1362-4962 J9 NUCLEIC ACIDS RES JI Nucleic Acids Res. PD JAN 4 PY 2016 VL 44 IS D1 BP D48 EP D50 DI 10.1093/nar/gkv1323 PG 3 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA DF3QY UT WOS:000371261700006 PM 26657633 ER PT J AU Kim, S Thiessen, PA Bolton, EE Chen, J Fu, G Gindulyte, A Han, LY He, JE He, SQ Shoemaker, BA Wang, JY Yu, B Zhang, J Bryant, SH AF Kim, Sunghwan Thiessen, Paul A. Bolton, Evan E. Chen, Jie Fu, Gang Gindulyte, Asta Han, Lianyi He, Jane He, Siqian Shoemaker, Benjamin A. Wang, Jiyao Yu, Bo Zhang, Jian Bryant, Stephen H. TI PubChem Substance and Compound databases SO NUCLEIC ACIDS RESEARCH LA English DT Article ID MOLECULAR SHAPE; SIMILARITY COEFFICIENTS; GAUSSIAN DESCRIPTION; INFORMATION-SYSTEM; 3-D SIMILARITY; RESOURCE; SMILES; COMPATIBILITY; GENERATION; IDENTIFIER AB PubChem (https://pubchem.ncbi.nlm.nih.gov) is a public repository for information on chemical substances and their biological activities, launched in 2004 as a component of the Molecular Libraries Roadmap Initiatives of the US National Institutes of Health (NIH). For the past 11 years, PubChem has grown to a sizable system, serving as a chemical information resource for the scientific research community. PubChem consists of three inter-linked databases, Substance, Compound and BioAssay. The Substance database contains chemical information deposited by individual data contributors to PubChem, and the Compound database stores unique chemical structures extracted from the Substance database. Biological activity data of chemical substances tested in assay experiments are contained in the BioAssay database. This paper provides an overview of the PubChem Substance and Compound databases, including data sources and contents, data organization, data submission using PubChem Upload, chemical structure standardization, web-based interfaces for textual and non-textual searches, and programmatic access. It also gives a brief description of PubChem3D, a resource derived from theoretical three-dimensional structures of compounds in PubChem, as well as PubChemRDF, Resource Description Framework (RDF)-formatted PubChem data for data sharing, analysis and integration with information contained in other databases. C1 [Kim, Sunghwan; Thiessen, Paul A.; Bolton, Evan E.; Chen, Jie; Fu, Gang; Gindulyte, Asta; Han, Lianyi; He, Jane; He, Siqian; Shoemaker, Benjamin A.; Wang, Jiyao; Yu, Bo; Zhang, Jian; Bryant, Stephen H.] NIH, Natl Ctr Biotechnol Informat, Natl Lib Med, US Dept HHS, Bethesda, MD 20894 USA. RP Bolton, EE (reprint author), NIH, Natl Ctr Biotechnol Informat, Natl Lib Med, US Dept HHS, Bethesda, MD 20894 USA. EM bolton@ncbi.nlm.nih.gov RI Kim, Sunghwan/A-6738-2008; Fu, Gang/F-8837-2016 OI Kim, Sunghwan/0000-0001-9828-2074; Fu, Gang/0000-0002-4860-8539 FU Intramural Research Program of the National Library of Medicine, National Institutes of Health FX Intramural Research Program of the National Library of Medicine, National Institutes of Health (in part). Funding for open access charge: Intramural Research Program of the National Library of Medicine, National Institutes of Health. NR 49 TC 116 Z9 116 U1 6 U2 16 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0305-1048 EI 1362-4962 J9 NUCLEIC ACIDS RES JI Nucleic Acids Res. PD JAN 4 PY 2016 VL 44 IS D1 BP D1202 EP D1213 DI 10.1093/nar/gkv951 PG 12 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA DF3QY UT WOS:000371261700170 PM 26400175 ER PT J AU Kitts, PA Church, DM Thibaud-Nissen, F Choi, J Hem, V Sapojnikov, V Smith, RG Tatusova, T Xiang, C Zherikov, A DiCuccio, M Murphy, TD Pruitt, KD Kimchi, A AF Kitts, Paul A. Church, Deanna M. Thibaud-Nissen, Francoise Choi, Jinna Hem, Vichet Sapojnikov, Victor Smith, Robert G. Tatusova, Tatiana Xiang, Charlie Zherikov, Andrey DiCuccio, Michael Murphy, Terence D. Pruitt, Kim D. Kimchi, Avi TI Assembly: a resource for assembled genomes at NCBI SO NUCLEIC ACIDS RESEARCH LA English DT Article ID READ ALIGNMENT; DRAFT GENOME; METABOLISM; SEQUENCE; METADATA; DATABASE AB The NCBI Assembly database (www.ncbi.nlm.nih.gov/assembly/) provides stable accessioning and data tracking for genome assembly data. The model underlying the database can accommodate a range of assembly structures, including sets of unordered contig or scaffold sequences, bacterial genomes consisting of a single complete chromosome, or complex structures such as a human genome with modeled allelic variation. The database provides an assembly accession and version to unambiguously identify the set of sequences that make up a particular version of an assembly, and tracks changes to updated genome assemblies. The Assembly database reports metadata such as assembly names, simple statistical reports of the assembly (number of contigs and scaffolds, contiguity metrics such as contig N50, total sequence length and total gap length) as well as the assembly update history. The Assembly database also tracks the relationship between an assembly submitted to the International Nucleotide Sequence Database Consortium (INSDC) and the assembly represented in the NCBI RefSeq project. Users can find assemblies of interest by querying the Assembly Resource directly or by browsing available assemblies for a particular organism. Links in the Assembly Resource allow users to easily download sequence and annotations for current versions of genome assemblies from the NCBI genomes FTP site. C1 [Kitts, Paul A.; Church, Deanna M.; Thibaud-Nissen, Francoise; Choi, Jinna; Hem, Vichet; Sapojnikov, Victor; Smith, Robert G.; Tatusova, Tatiana; Xiang, Charlie; Zherikov, Andrey; DiCuccio, Michael; Murphy, Terence D.; Pruitt, Kim D.; Kimchi, Avi] NIH, Natl Ctr Biotechnol Informat, Natl Lib Med, Bethesda, MD 20894 USA. [Church, Deanna M.] Personalis Inc, Menlo Pk, CA 94025 USA. RP Kitts, PA (reprint author), NIH, Natl Ctr Biotechnol Informat, Natl Lib Med, Bethesda, MD 20894 USA. EM kitts@ncbi.nlm.nih.gov FU National Library of Medicine; National Institutes of Health FX Intramural Research Program of the National Library of Medicine; National Institutes of Health. Funding for open access charge: Intramural Research Program of the National Library of Medicine; National Institutes of Health. NR 23 TC 10 Z9 10 U1 1 U2 3 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0305-1048 EI 1362-4962 J9 NUCLEIC ACIDS RES JI Nucleic Acids Res. PD JAN 4 PY 2016 VL 44 IS D1 BP D73 EP D80 DI 10.1093/nar/gkv1226 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA DF3QY UT WOS:000371261700010 PM 26578580 ER PT J AU Landrum, MJ Lee, JM Benson, M Brown, G Chao, C Chitipiralla, S Gu, B Hart, J Hoffman, D Hoover, J Jang, W Katz, K Ovetsky, M Riley, G Sethi, A Tully, R Villamarin-Salomon, R Rubinstein, W Maglott, DR AF Landrum, Melissa J. Lee, Jennifer M. Benson, Mark Brown, Garth Chao, Chen Chitipiralla, Shanmuga Gu, Baoshan Hart, Jennifer Hoffman, Douglas Hoover, Jeffrey Jang, Wonhee Katz, Kenneth Ovetsky, Michael Riley, George Sethi, Amanjeev Tully, Ray Villamarin-Salomon, Ricardo Rubinstein, Wendy Maglott, Donna R. TI ClinVar: public archive of interpretations of clinically relevant variants SO NUCLEIC ACIDS RESEARCH LA English DT Article ID HUMAN PHENOTYPE; ONTOLOGY AB ClinVar (https://www.ncbi.nlm.nih.gov/clinvar/) at the National Center for Biotechnology Information (NCBI) is a freely available archive for interpretations of clinical significance of variants for reported conditions. The database includes germline and somatic variants of any size, type or genomic location. Interpretations are submitted by clinical testing laboratories, research laboratories, locus-specific databases, OMIM (R), GeneReviews (TM), UniProt, expert panels and practice guidelines. In NCBI's Variation submission portal, submitters upload batch submissions or use the Submission Wizard for single submissions. Each submitted interpretation is assigned an accession number prefixed with SCV. ClinVar staff review validation reports with data types such as HGVS (Human Genome Variation Society) expressions; however, clinical significance is reported directly from submitters. Interpretations are aggregated by variant-condition combination and assigned an accession number prefixed with RCV. Clinical significance is calculated for the aggregate record, indicating consensus or conflict in the submitted interpretations. ClinVar uses data standards, such as HGVS nomenclature for variants and MedGen identifiers for conditions. The data are available on the web as variant-specific views; the entire data set can be downloaded via ftp. Programmatic access for ClinVar records is available through NCBI's E-utilities. Future development includes providing a variant-centric XML archive and a web page for details of SCV submissions. C1 [Landrum, Melissa J.; Lee, Jennifer M.; Benson, Mark; Brown, Garth; Chao, Chen; Chitipiralla, Shanmuga; Gu, Baoshan; Hart, Jennifer; Hoffman, Douglas; Hoover, Jeffrey; Jang, Wonhee; Katz, Kenneth; Ovetsky, Michael; Riley, George; Sethi, Amanjeev; Tully, Ray; Villamarin-Salomon, Ricardo; Rubinstein, Wendy; Maglott, Donna R.] NIH, Natl Ctr Biotechnol Informat, Natl Lib Med, Bethesda, MD 20893 USA. RP Landrum, MJ (reprint author), NIH, Natl Ctr Biotechnol Informat, Natl Lib Med, Bethesda, MD 20893 USA. EM landrum@ncbi.nlm.nih.gov FU Intramural Research Program of the National Institutes of Health, National Library of Medicine FX Funding for open access charge: Intramural Research Program of the National Institutes of Health, National Library of Medicine. NR 15 TC 78 Z9 79 U1 5 U2 6 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0305-1048 EI 1362-4962 J9 NUCLEIC ACIDS RES JI Nucleic Acids Res. PD JAN 4 PY 2016 VL 44 IS D1 BP D862 EP D868 DI 10.1093/nar/gkv1222 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA DF3QY UT WOS:000371261700122 PM 26582918 ER PT J AU Li, MJ Liu, ZP Wang, PW Wong, MP Nelson, MR Kocher, JPA Yeager, M Sham, PC Chanock, SJ Xia, ZY Wang, JW AF Li, Mulin Jun Liu, Zipeng Wang, Panwen Wong, Maria P. Nelson, Matthew R. Kocher, Jean-Pierre A. Yeager, Meredith Sham, Pak Chung Chanock, Stephen J. Xia, Zhengyuan Wang, Junwen TI GWASdb v2: an update database for human genetic variants identified by genome-wide association studies SO NUCLEIC ACIDS RESEARCH LA English DT Article ID COMPLEX TRAITS; DISEASE-ONTOLOGY; EXONIC VARIANTS; HUMAN PHENOTYPE; ANNOTATION; RESOURCE; SNPS; METAANALYSIS; INFORMATION; CHALLENGES AB Genome-wide association studies (GWASs), now as a routine approach to study single-nucleotide polymorphism (SNP)-trait association, have uncovered over ten thousand significant trait/disease associated SNPs (TASs). Here, we updated GWASdb (GWASdb v2, http://jjwanglab.org/gwasdb) which provides comprehensive data curation and knowledge integration for GWAS TASs. These updates include: (i) Up to August 2015, we collected 2479 unique publications from PubMed and other resources; (ii) We further curated moderate SNP-trait associations (P-value < 1.0x10(-3)) from each original publication, and generated a total of 252 530 unique TASs in all GWASdb v2 collected studies; (iii) We manually mapped 1610 GWAS traits to 501 Human Phenotype Ontology (HPO) terms, 435 Disease Ontology (DO) terms and 228 Disease Ontology Lite (DOLite) terms. For each ontology term, we also predicted the putative causal genes; (iv) We curated the detailed sub-populations and related sample size for each study; (v) Importantly, we performed extensive function annotation for each TAS by incorporating gene-based information, ENCODE ChIP-seq assays, eQTL, population haplotype, functional prediction across multiple biological domains, evolutionary signals and disease-related annotation; (vi) Addition-ally, we compiled a SNP-drug response association dataset for 650 pharmacogenetic studies involving 257 drugs in this update; (vii) Last, we improved the user interface of website. C1 [Li, Mulin Jun; Liu, Zipeng; Wang, Panwen; Sham, Pak Chung; Wang, Junwen] Univ Hong Kong, LKS Fac Med, Ctr Genom Sci, Hong Kong, Hong Kong, Peoples R China. [Li, Mulin Jun; Wang, Panwen; Sham, Pak Chung; Wang, Junwen] Univ Hong Kong, LKS Fac Med, Sch Biomed Sci, Hong Kong, Hong Kong, Peoples R China. [Liu, Zipeng; Xia, Zhengyuan] Univ Hong Kong, LKS Fac Med, Dept Anaesthesiol, Hong Kong, Hong Kong, Peoples R China. [Wong, Maria P.] Univ Hong Kong, LKS Fac Med, Dept Pathol, Hong Kong, Hong Kong, Peoples R China. [Nelson, Matthew R.] GlaxoSmithKline, Quantitat Sci, Res Triangle Pk, NC USA. [Kocher, Jean-Pierre A.] Mayo Clin, Coll Med, Div Biomed Stat & Informat, Rochester, MN USA. [Yeager, Meredith; Chanock, Stephen J.] NCI, Div Canc Epidemiol & Genet, NIH, Bethesda, MD 20892 USA. [Sham, Pak Chung] Univ Hong Kong, LKS Fac Med, State Key Lab Brain & Cognit Sci, Hong Kong, Hong Kong, Peoples R China. [Sham, Pak Chung] Univ Hong Kong, LKS Fac Med, Dept Psychiat, Hong Kong, Hong Kong, Peoples R China. RP Wang, JW (reprint author), Univ Hong Kong, LKS Fac Med, Ctr Genom Sci, Hong Kong, Hong Kong, Peoples R China.; Wang, JW (reprint author), Univ Hong Kong, LKS Fac Med, Sch Biomed Sci, Hong Kong, Hong Kong, Peoples R China. EM junwen@uw.edu RI Wang, Junwen/D-3700-2011 OI Wang, Junwen/0000-0002-4432-4707 FU Research Grants Council, Hong Kong SAR, China [17121414M, 17124614M]; National Natural Science Foundation of China [91229105, 81572786, 9152930007] FX Research Grants Council, Hong Kong SAR, China [17121414M, 17124614M]; National Natural Science Foundation of China [91229105, 81572786, 9152930007]. Funding for open access: National Natural Science Foundation of China [91229105]. NR 61 TC 16 Z9 16 U1 4 U2 9 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0305-1048 EI 1362-4962 J9 NUCLEIC ACIDS RES JI Nucleic Acids Res. PD JAN 4 PY 2016 VL 44 IS D1 BP D869 EP D876 DI 10.1093/nar/gkv1317 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA DF3QY UT WOS:000371261700123 PM 26615194 ER PT J AU Lichtenberg, J Heuston, EF Mishra, T Keller, CA Hardison, RC Bodine, DM AF Lichtenberg, Jens Heuston, Elisabeth F. Mishra, Tejaswini Keller, Cheryl A. Hardison, Ross C. Bodine, David M. TI SBR-Blood: systems biology repository for hematopoietic cells SO NUCLEIC ACIDS RESEARCH LA English DT Article ID GENE-EXPRESSION; RNA-SEQ; TRANSCRIPTIONAL REGULATION; VERTEBRATE ERYTHROPOIESIS; PROGENITOR CELLS; HUMAN GENOME; DATABASE; HIERARCHY; BINDING; EPODB AB Extensive research into hematopoiesis (the development of blood cells) over several decades has generated large sets of expression and epigenetic profiles in multiple human and mouse blood cell types. However, there is no single location to analyze how gene regulatory processes lead to different mature blood cells. We have developed a new database framework called hematopoietic Systems Biology Repository (SBR-Blood), available online at http://sbrblood.nhgri.nih.gov, which allows user-initiated analyses for cell type correlations or gene-specific behavior during differentiation using publicly available datasets for array-and sequencing-based platforms from mouse hematopoietic cells. SBR-Blood organizes information by both cell identity and by hematopoietic lineage. The validity and usability of SBR-Blood has been established through the reproduction of workflows relevant to expression data, DNA methylation, histone modifications and transcription factor occupancy profiles. C1 [Lichtenberg, Jens; Heuston, Elisabeth F.; Bodine, David M.] NHGRI, NIH, Bethesda, MD 20892 USA. [Mishra, Tejaswini; Keller, Cheryl A.; Hardison, Ross C.] Penn State Univ, Dept Biochem & Mol Biol, University Pk, PA USA. RP Lichtenberg, J (reprint author), NHGRI, NIH, Bethesda, MD 20892 USA. EM lichtenbergj@mail.nih.gov OI Heuston, Elisabeth/0000-0002-1603-4083 FU National Human Genome Research Institute (NHGRI) intramural funds FX National Human Genome Research Institute (NHGRI) intramural funds. Funding for open access charge: NHGRI intramural funds. NR 42 TC 0 Z9 0 U1 1 U2 3 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0305-1048 EI 1362-4962 J9 NUCLEIC ACIDS RES JI Nucleic Acids Res. PD JAN 4 PY 2016 VL 44 IS D1 BP D925 EP D931 DI 10.1093/nar/gkv1263 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA DF3QY UT WOS:000371261700131 PM 26590403 ER PT J AU Pirtskhalava, M Gabrielian, A Cruz, P Griggs, HL Squires, RB Hurt, DE Grigolava, M Chubinidze, M Gogoladze, G Vishnepolsky, B Alekseev, V Rosenthal, A Tartakovsky, M AF Pirtskhalava, Malak Gabrielian, Andrei Cruz, Phillip Griggs, Hannah L. Squires, R. Burke Hurt, Darrell E. Grigolava, Maia Chubinidze, Mindia Gogoladze, George Vishnepolsky, Boris Alekseev, Vsevolod Rosenthal, Alex Tartakovsky, Michael TI DBAASP v.2: an enhanced database of structure and antimicrobial/cytotoxic activity of natural and synthetic peptides SO NUCLEIC ACIDS RESEARCH LA English DT Article ID MANUALLY CURATED DATABASE; SEQUENCES; INFORMATION; MEMBRANES; DYNAMICS; PROGRAM AB Antimicrobial peptides (AMPs) are anti-infectives that may represent a novel and untapped class of biotherapeutics. Increasing interest in AMPs means that new peptides (natural and synthetic) are discovered faster than ever before. We describe herein a new version of the Database of Antimicrobial Activity and Structure of Peptides (DBAASPv.2, which is freely accessible at http://dbaasp.org). This iteration of the database reports chemical structures and empirically-determined activities (MICs, IC50, etc.) against more than 4200 specific target microbes for more than 2000 ribosomal, 80 non-ribosomal and 5700 synthetic peptides. Of these, the vast majority are monomeric, but nearly 200 of these peptides are found as homo-or heterodimers. More than 6100 of the peptides are linear, but about 515 are cyclic and more than 1300 have other intra-chain covalent bonds. More than half of the entries in the database were added after the resource was initially described, which reflects the recent sharp uptick of interest in AMPs. New features of DBAASPv. 2 include: (i) user-friendly utilities and reporting functions, (ii)a 'Ranking Search' function to query the database by target species and return a ranked list of peptides with activity against that target and (iii) structural descriptions of the peptides derived from empirical data or calculated by molecular dynamics (MD) simulations. The three-dimensional structural data are critical components for understanding structure-activity relationships and for design of new antimicrobial drugs. We created more than 300 high-throughput MD simulations specifically for inclusion in DBAASP. The resulting structures are described in the database by novel trajectory analysis plots and movies. Another 200+ DBAASP entries have links to the Protein DataBank. All of the structures are easily visualized directly in the web browser. C1 [Pirtskhalava, Malak; Grigolava, Maia; Chubinidze, Mindia; Gogoladze, George; Vishnepolsky, Boris] Ivane Beritashvili Ctr Expt Biomed, GA-0160 Tbilisi, Rep of Georgia. [Gabrielian, Andrei; Cruz, Phillip; Griggs, Hannah L.; Squires, R. Burke; Hurt, Darrell E.; Alekseev, Vsevolod; Rosenthal, Alex; Tartakovsky, Michael] NIAID, Office Cyber Infrastruct & Computat Biol, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA. RP Pirtskhalava, M (reprint author), Ivane Beritashvili Ctr Expt Biomed, GA-0160 Tbilisi, Rep of Georgia. EM m.pirtskhalava@lifescience.org.ge OI Squires, R Burke/0000-0001-9666-6285 FU International Science and Technology Center through National Institute of Allergy and Infectious Diseases/National Institutes of Health [G-2102]; Shota Rustaveli National Science Foundation [FR/397/7-180/14]; International Science and Technology Center [G-2102] FX International Science and Technology Center provided through National Institute of Allergy and Infectious Diseases/National Institutes of Health [G-2102 to M.P., M.G., M.C., G.G., B.V.]; Shota Rustaveli National Science Foundation [FR/397/7-180/14 to M.P., M.G., G.G., B.V.]. Funding for open access charge: International Science and Technology Center [G-2102]. NR 30 TC 5 Z9 5 U1 3 U2 11 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0305-1048 EI 1362-4962 J9 NUCLEIC ACIDS RES JI Nucleic Acids Res. PD JAN 4 PY 2016 VL 44 IS D1 BP D1104 EP D1112 DI 10.1093/nar/gkv1174 PG 9 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA DF3QY UT WOS:000371261700156 PM 26578581 ER PT J AU Rigden, DJ Fernandez-Suarez, XM Galperin, MY AF Rigden, Daniel J. Fernandez-Suarez, Xose M. Galperin, Michael Y. TI The 2016 database issue of Nucleic Acids Research and an updated molecular biology database collection SO NUCLEIC ACIDS RESEARCH LA English DT Article AB The 2016 Database Issue of Nucleic Acids Research starts with overviews of the resources provided by three major bioinformatics centers, the U.S. National Center for Biotechnology Information (NCBI), the European Bioinformatics Institute (EMBL-EBI) and Swiss Institute for Bioinformatics (SIB). Also included are descriptions of 62 new databases and updates on 95 databases that have been previously featured in NAR plus 17 previously described elsewhere. A number of papers in this issue deal with resources on nucleic acids, including various kinds of non-coding RNAs and their interactions, molecular dynamics simulations of nucleic acid structure, and two databases of super-enhancers. The protein database section features important updates on the EBI's Pfam, PDBe and PRIDE databases, as well as a variety of resources on pathways, metabolomics and metabolic modeling. This issue also includes updates on popular metagenomics resources, such as MG-RAST, EBI Metagenomics, and probeBASE, as well as a newly compiled Human Pan-Microbe Communities database. A significant fraction of the new and updated databases are dedicated to the genetic basis of disease, primarily cancer, and various aspects of drug research, including resources for patented drugs, their side effects, withdrawn drugs, and potential drug targets. A further six papers present updated databases of various antimicrobial and anticancer peptides. The entire Database Issue is freely available online on the Nucleic Acids Research website (http://nar.oxfordjournals.org/). The NAR online Molecular Biology Database Collection, http: //www.oxfordjournals.org/nar/database/c/, has been updated with the addition of 88 new resources and removal of 23 obsolete websites, which brought the current listing to 1685 databases. C1 [Rigden, Daniel J.] Univ Liverpool, Inst Integrat Biol, Crown St, Liverpool L69 7ZB, Merseyside, England. [Fernandez-Suarez, Xose M.] Thermo Fisher Sci, Inchinnan Business Pk, Paisley PA4 9RF, Renfrew, Scotland. [Galperin, Michael Y.] NIH, Natl Ctr Biotechnol Informat, Natl Lib Med, Bethesda, MD 20894 USA. RP Rigden, DJ (reprint author), Univ Liverpool, Inst Integrat Biol, Crown St, Liverpool L69 7ZB, Merseyside, England.; Galperin, MY (reprint author), NIH, Natl Ctr Biotechnol Informat, Natl Lib Med, Bethesda, MD 20894 USA. EM drigden@liv.ac.uk; nardatabase@gmail.com OI Galperin, Michael/0000-0002-2265-5572 FU NIH Intramural Research Program at the National Library of Medicine; Oxford University Press - NAR FX The NIH Intramural Research Program at the National Library of Medicine [to M.Y.G.]. The open access publication charge for this paper has been waived by Oxford University Press - NAR. NR 53 TC 8 Z9 9 U1 1 U2 7 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0305-1048 EI 1362-4962 J9 NUCLEIC ACIDS RES JI Nucleic Acids Res. PD JAN 4 PY 2016 VL 44 IS D1 BP D1 EP D6 DI 10.1093/nar/gkv1356 PG 6 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA DF3QY UT WOS:000371261700001 PM 26740669 ER PT J AU Varshney, GK Zhang, SY Pei, WH Adomako-Ankomah, A Fohtung, J Schaffer, K Carrington, B Maskeri, A Slevin, C Wolfsberg, T Ledin, J Sood, R Burgess, SM AF Varshney, Gaurav K. Zhang, Suiyuan Pei, Wuhong Adomako-Ankomah, Ashrifia Fohtung, Jacob Schaffer, Katherine Carrington, Blake Maskeri, Anoo Slevin, Claire Wolfsberg, Tyra Ledin, Johan Sood, Raman Burgess, Shawn M. TI CRISPRz: a database of zebrafish validated sgRNAs SO NUCLEIC ACIDS RESEARCH LA English DT Article ID KNOCK-IN; SYSTEM; DNA; IMMUNITY; CAS9; GENERATION; NUCLEASE; PRECISE AB CRISPRz (http://research.nhgri.nih.gov/CRISPRz/) is a database of CRISPR/Cas9 target sequences that have been experimentally validated in zebrafish. Programmable RNA-guided CRISPR/Cas9 has recently emerged as a simple and efficient genome editing method in various cell types and organisms, including zebrafish. Because the technique is so easy and efficient in zebrafish, the most valuable asset is no longer a mutated fish (which has distribution challenges), but rather a CRISPR/Cas9 target sequence to the gene confirmed to have high mutagenic efficiency. With a highly active CRISPR target, a mutant fish can be quickly replicated in any genetic background anywhere in the world. However, sgRNA's vary widely in their activity and models for predicting target activity are imperfect. Thus, it is very useful to collect in one place validated CRISPR target sequences with their relative mutagenic activities. A researcher could then select a target of interest in the database with an expected activity. Here, we report the development of CRISPRz, a database of validated zebrafish CRISPR target sites collected from published sources, as well as from our own in-house large-scale mutagenesis project. CRISPRz can be searched using multiple inputs such as ZFIN IDs, accession number, UniGene ID, or gene symbols from zebrafish, human and mouse. C1 [Varshney, Gaurav K.; Pei, Wuhong; Adomako-Ankomah, Ashrifia; Fohtung, Jacob; Schaffer, Katherine; Maskeri, Anoo; Slevin, Claire; Burgess, Shawn M.] NHGRI, Translat & Funct Genom Branch, NIH, Bethesda, MD 20892 USA. [Zhang, Suiyuan; Wolfsberg, Tyra] NHGRI, Computat & Stat Genom Branch, NIH, Bethesda, MD 20892 USA. [Carrington, Blake; Sood, Raman] NHGRI, Zebrafish Core, Translat & Funct Genom Branch, NIH, Bethesda, MD 20892 USA. [Ledin, Johan] Uppsala Univ, Sci Life Lab, Dept Organismal Biol, SE-75236 Uppsala, Sweden. RP Burgess, SM (reprint author), NHGRI, Translat & Funct Genom Branch, NIH, Bethesda, MD 20892 USA. EM burgess@mail.nih.gov OI Ledin, Johan/0000-0002-7319-7735 FU Intramural Research Program of the National Human Genome Research Institute; National Institutes of Health [1ZIAHG000183-14] FX Intramural Research Program of the National Human Genome Research Institute; National Institutes of Health [1ZIAHG000183-14]. Funding for open access charge: The Intramural Research Program of the National Human Genome Research Institute; National Institutes of Health [1ZIAHG000183-14]. NR 30 TC 7 Z9 7 U1 2 U2 9 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0305-1048 EI 1362-4962 J9 NUCLEIC ACIDS RES JI Nucleic Acids Res. PD JAN 4 PY 2016 VL 44 IS D1 BP D822 EP D826 DI 10.1093/nar/gkv998 PG 5 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA DF3QY UT WOS:000371261700116 PM 26438539 ER PT J AU Zheng, ZJ Goncearenco, A Berezovsky, IN AF Zheng, Zejun Goncearenco, Alexander Berezovsky, Igor N. TI Nucleotide binding database NBDB - a collection of sequence motifs with specific protein-ligand interactions SO NUCLEIC ACIDS RESEARCH LA English DT Article ID ELEMENTARY FUNCTIONAL LOOPS; NADP-DEPENDENT ENZYMES; STRUCTURAL CLASSIFICATION; ORGANIC COFACTORS; FOLD SPACE; EVOLUTION; SITES; COMPLEXES; COMMON; FAD AB NBDB database describes proteinmotifs, elementary functional loops (EFLs) that are involved in binding of nucleotide-containing ligands and other biologically relevant cofactors/coenzymes, including ATP, AMP, ATP, GMP, GDP, GTP, CTP, PAP, PPS, FMN, FAD(H), NAD(H), NADP, cAMP, cGMP, c-di-AMP and c-di-GMP, ThPP, THD, F-420, ACO, CoA, PLP and SAM. The database is freely available online at http://nbdb.bii.a-star.edu.sg. In total, NBDB contains data on 249 motifs that work in interactions with 24 ligands. Sequence profiles of EFL motifs were derived de novo from nonredundant Uniprot proteome sequences. Conserved amino acid residues in the profiles interact specifically with distinct chemical parts of nucleotide-containing ligands, such as nitrogenous bases, phosphate groups, ribose, nicotinamide, and flavin moieties. Each EFL profile in the database is characterized by a pattern of corresponding ligand-protein interactions found in crystallized ligand-protein complexes. NBDB database helps to explore the determinants of nucleotide and cofactor binding in different protein folds and families. NBDB can also detect fragments that match to profiles of particular EFLs in the protein sequence provided by user. Comprehensive information on sequence, structures, and interactions of EFLs with ligands provides a foundation for experimental and computational efforts on design of required protein functions. C1 [Zheng, Zejun; Berezovsky, Igor N.] ASTAR, Bioinformat Inst, 30 Biopolis St,07-01 Matrix, Singapore 138671, Singapore. [Goncearenco, Alexander] Univ Bergen, Dept Informat, Computat Biol Unit, N-5020 Bergen, Norway. [Berezovsky, Igor N.] Natl Univ Singapore, DBS, 8 Med Dr, Singapore 117579, Singapore. [Goncearenco, Alexander] Natl Lib Med, Natl Ctr Biotechnol Informat, Computat Biol Branch, Bethesda, MD 20894 USA. RP Berezovsky, IN (reprint author), ASTAR, Bioinformat Inst, 30 Biopolis St,07-01 Matrix, Singapore 138671, Singapore.; Berezovsky, IN (reprint author), Natl Univ Singapore, DBS, 8 Med Dr, Singapore 117579, Singapore. EM igorb@bii.a-star.edu.sg RI Goncearenco, Alexander/M-3946-2015 OI Goncearenco, Alexander/0000-0002-9738-7146 FU Bioinformatics Institute, A*STAR FX Funding for open access charges: Bioinformatics Institute, A*STAR. NR 36 TC 3 Z9 3 U1 3 U2 8 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0305-1048 EI 1362-4962 J9 NUCLEIC ACIDS RES JI Nucleic Acids Res. PD JAN 4 PY 2016 VL 44 IS D1 BP D301 EP D307 DI 10.1093/nar/gkv1124 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA DF3QY UT WOS:000371261700041 PM 26507856 ER PT J AU Kraus, A AF Kraus, Allison TI Proline and lysine residues provide modulatory switches in amyloid formation: Insights from prion protein SO PRION LA English DT Article DE lysine; prion protein; proline; amyloid ID PRP AMYLOIDS; IN-VITRO; SUBSTRATE; PEPTIDES; COFACTOR; FIBRILS; CLUSTER AB Amyloidogenic proteins have an increased propensity to reorganize into the highly structured, beta sheet rich structures that characterize amyloid. The probability of attaining these highly structured assemblies is influenced by multiple factors, including amino acid composition and environmental conditions. Evolutionary selection for amino acid sequences that prevent amyloid formation could further modulate amyloid-forming propensity. Indeed, we have recently identified specific proline and lysine residues, contained within a highly conserved central region of prion protein (PrP), that impede PrP amyloid formation in vitro. These prolines are mutated in certain forms of the human familial genetic disease, Gerstmann-Straussler-Schneiker (GSS) syndrome. Here, I discuss the influence of these proline and lysine residues on PrP amyloid formation and how such anti-amyloidogenic primary amino acid sequences might be modulated to influence protein amyloidogenicity. C1 [Kraus, Allison] NIAID, Lab Persistant Viral Dis, Rocky Mt Labs, NIH, Hamilton, MT USA. RP Kraus, A (reprint author), Rocky Mt Labs, 903 S 4th St, Hamilton, MT 59840 USA. EM Allison.kraus@nih.gov FU Intramural Research Program of the National Institute of Allergy and Infectious Diseases FX This work was supported by the Intramural Research Program of the National Institute of Allergy and Infectious Diseases. NR 28 TC 1 Z9 1 U1 3 U2 7 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 JAN 2 PY 2016 VL 10 IS 1 BP 57 EP 62 DI 10.1080/19336896.2015.1132138 PG 6 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA DI1WA UT WOS:000373286100007 PM 26864641 ER PT J AU Kitsantas, P Aguisanda, F AF Kitsantas, Panagiota Aguisanda, Francis TI Association of asthma with obesity among adolescents exposed to environmental tobacco smoke SO JOURNAL OF ASTHMA LA English DT Article DE environmental tobacco smoke; asthma; public health; exposure; childhood obesity; Adolescents ID BODY-MASS INDEX; UNITED-STATES; CHILDREN; PREVALENCE; CHILDHOOD; WEIGHT; HEALTH; RISK AB Objective: The purpose of this study was to examine the association between asthma diagnosis and obesity among adolescents exposed to environmental tobacco smoke (ETS). Methods: The sample included 28 807 adolescents (13-17 years old) from the National Survey of Children's Health (NSCH) (2011-2012). Study design: The NSCH is a US cross-sectional telephone survey that included at least one child between the ages of 0 and 17 years residing at a household during the time of the interview. Descriptive statistics were used to describe sample characteristics and assess the prevalence of asthma among adolescents with obesity exposed to ETS. Logistic regression models were built to assess the effect of obesity on asthma diagnosis within the context of ETS exposure. Results: The prevalence of asthma among adolescents was 10.4% and the obesity was 13.2%. Adolescents with obesity exposed to ETS within the home were significantly (p < 0.05) more likely to have an asthma diagnosis (23%) compared with non-obese (10.9%) residing in similar households. Adjusted odds ratios showed that adolescents with obesity were 2.07 (95% CI, 1.15, 3.70) times more likely to have asthma if they were exposed to ETS inside their homes. Conclusion: The findings indicate that adolescents with obesity are more likely to be diagnosed with asthma if they are exposed to ETS in the household. It is important that the association between obesity and asthma is examined within the context of environmental risk factors in future studies, as this may shed some light to underlying mechanisms between these two serious public health issues. C1 [Kitsantas, Panagiota] George Mason Univ, Dept Hlth Adm & Policy, MS 1J3,4400 Univ Dr, Fairfax, VA 22030 USA. [Aguisanda, Francis] NIH, Natl Ctr Adv Translat Sci, Rockville, MD USA. RP Kitsantas, P (reprint author), George Mason Univ, Dept Hlth Adm & Policy, MS 1J3,4400 Univ Dr, Fairfax, VA 22030 USA. EM pkitsant@gmu.edu NR 23 TC 0 Z9 0 U1 2 U2 2 PU TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXON, ENGLAND SN 0277-0903 EI 1532-4303 J9 J ASTHMA JI J. Asthma PD JAN 2 PY 2016 VL 53 IS 1 BP 25 EP 29 DI 10.3109/02770903.2015.1024322 PG 5 WC Allergy; Respiratory System SC Allergy; Respiratory System GA DG9QP UT WOS:000372419200006 PM 26365093 ER PT J AU Elahi, D Ruff, DA Carlson, OD Meneilly, GS Habener, JF Egan, JM AF Elahi, Dariush Ruff, Dennis A. Carlson, Olga D. Meneilly, Graydon S. Habener, Joel F. Egan, Josephine M. TI Does GLP-1 suppress its own basal secretion? SO ENDOCRINE RESEARCH LA English DT Article DE GLP-1; glucose clamp; insulin; negative feedback ID GLUCAGON-LIKE PEPTIDE-1; INSULIN-SECRETION; INHIBITION; HUMANS; SOMATOSTATIN; SPECIFICITY; RELEASE; OBESITY; AMIDE; STATE AB Purpose/Aim: Negative feedback controls in endocrine regulatory systems are well recognized. The incretins and their role in glucose regulation have been of major interest recently. Whether the same negative control system applies to the regulation of incretin secretion is not clear. We sought to examine the hypothesis that exogenous administration of glucagon like peptide-1, GLP-1(7-36) amide or its metabolite GLP-1(9-36) amide, reduces the endogenous basal release of this incretin. Materials and Methods: We evaluated the endogenous basal release of GLP-1 using two separate study designs. In protocol A we examined the GLP-1(7-36) amide levels during the infusion of GLP-1(9-36) amide. In protocol B, we used PYY and GLP-2 as biomarkers for the endogenous basal release of GLP-1(7-36) amide and assessed the endogenous basal release of these two hormones during the GLP-1(7-36) infusion. Twelve lean and 12 obese subjects were enrolled in protocol A and 10 obese volunteers in protocol B. Results: The plasma levels of GLP-1(7-36) amide in protocol A and PYY and GLP-2 in protocol B remained unchanged during the exogenous infusion of GLP-1(9-36) and GLP-1(7-36) amide, respectively. Conclusions: The negative feedback control system as described by inhibition of the release of endogenous hormone while infusing it exogenously was not observed for the basal secretion of GLP-1(7-36) amide. C1 [Elahi, Dariush; Ruff, Dennis A.] ICON Early Phase Serv LLC, 8307 Gault Lane, San Antonio, TX 78209 USA. [Carlson, Olga D.; Egan, Josephine M.] NIA, Diabet Sect, Baltimore, MD 21224 USA. [Meneilly, Graydon S.] Univ British Columbia, Dept Med, Sch Med, Vancouver, BC, Canada. [Habener, Joel F.] Harvard Univ, Sch Med, Dept Med, Boston, MA USA. [Habener, Joel F.] Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Elahi, D (reprint author), ICON Early Phase Serv LLC, 8307 Gault Lane, San Antonio, TX 78209 USA. EM dariush.elahi@iconplc.com FU National Institutes of Health (NIH) [AG 00599, AG 623175, DK 30834]; Intramural Research Program of NIA; Alan McGavin Geriatric Medicine Endowment of University of British Columbia FX Authors have nothing to declare. This work has been supported in part by the National Institutes of Health (NIH) Grants: AG 00599, AG 623175, DK 30834 and by the Intramural Research Program of NIA. We gratefully acknowledge the support of the Alan McGavin Geriatric Medicine Endowment of the University of British Columbia. NR 27 TC 1 Z9 1 U1 1 U2 1 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 530 WALNUT STREET, STE 850, PHILADELPHIA, PA 19106 USA SN 0743-5800 EI 1532-4206 J9 ENDOCR RES JI Endocr. Res. PD JAN 2 PY 2016 VL 41 IS 1 BP 16 EP 20 DI 10.3109/07435800.2015.1038353 PG 5 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA DG4AT UT WOS:000372013000003 PM 26186406 ER PT J AU Duncan, JL Biswas, P Kozak, I Navani, M Syed, R Soudry, S Menghini, M Caruso, RC Jeffrey, BG Heckenlively, JR Reddy, GB Lee, P Roorda, A Ayyagari, R AF Duncan, Jacque L. Biswas, Pooja Kozak, Igor Navani, Mili Syed, Reema Soudry, Shiri Menghini, Moreno Caruso, Rafael C. Jeffrey, Brett G. Heckenlively, John R. Reddy, G. Bhanuprakash Lee, Pauline Roorda, Austin Ayyagari, Radha TI Ocular Phenotype of a Family with FAM161A-associated Retinal Degeneration SO OPHTHALMIC GENETICS LA English DT Article DE Exome sequencing; FAM161A; retinal degeneration ID RECESSIVE RETINITIS-PIGMENTOSA; INDIAN FAMILY; FAM161A; GENE; IDENTIFICATION; MUTATION; DISEASE; LOCUS AB Background: Characterization of retinal degeneration (RD) using high-resolution retinal imaging and exome sequencing may identify phenotypic features that correspond with specific genetic defects.Materials and Methods: Six members from a non-consanguineous Indian family (three affected siblings, their asymptomatic parents and an asymptomatic child) were characterized clinically, using visual acuity, perimetry, full-field electroretinography (ERG), optical coherence tomography and cone structure as outcome measures. Cone photoreceptors were imaged in the proband using adaptive optics scanning laser ophthalmoscopy. The exome was captured using Nimblegen SeqCap EZ V3.0 probes and sequenced using lllumina HiSeq. Reads were mapped to reference hg19. Confirmation of variants and segregation analysis was performed using dideoxy sequencing.Results: Analysis of exome variants using exomeSuite identified five homozygous variants in four genes known to be associated with RD. Further analysis revealed a homozygous nonsense mutation, c.1105 C>T, p.Arg335Ter, in the FAM161A gene segregating with RD. Three additional variants were found to occur at high frequency. Affected members showed a range of disease severity beginning at different ages, but all developed severe visual field and outer retinal loss.Conclusions: Exome analysis revealed a nonsense homozygous mutation in FAM161A segregating with RD with severe vision loss and a range of disease onset and progression. Loss of outer retinal structures demonstrated with high-resolution retinal imaging suggests FAM161A is important for normal photoreceptor structure and survival. Exome sequencing may identify causative genetic variants in autosomal recessive RD families when other genetic test strategies fail to identify a mutation. C1 [Duncan, Jacque L.; Syed, Reema; Soudry, Shiri; Menghini, Moreno] Univ Calif San Francisco, Dept Ophthalmol, San Francisco, CA USA. [Biswas, Pooja; Kozak, Igor; Navani, Mili; Lee, Pauline; Ayyagari, Radha] Univ Calif San Diego, Shiley Eye Ctr, La Jolla, CA 92093 USA. [Caruso, Rafael C.; Jeffrey, Brett G.] NEI, NIH, Bethesda, MD 20892 USA. [Caruso, Rafael C.] Princeton Univ, Princeton Neurosci Inst, Princeton, NJ 08544 USA. [Heckenlively, John R.] Univ Michigan, Dept Ophthalmol, Ann Arbor, MI USA. [Reddy, G. Bhanuprakash] Indian Council Med Res, Natl Inst Nutr, Jamai Osmania Po, Hyderabad 500007, Andhra Pradesh, India. [Lee, Pauline] Scripps Res Inst, Dept Mol & Expt Med, 10666 N Torrey Pines Rd, La Jolla, CA 92037 USA. [Roorda, Austin] Univ Calif Berkeley, Sch Optometry, Berkeley, CA 94720 USA. [Roorda, Austin; Ayyagari, Radha] Univ Calif Berkeley, Vis Sci Grad Grp, Berkeley, CA 94720 USA. RP Ayyagari, R (reprint author), Univ Calif San Diego, Jacobs Retina Ctr, Shiley Eye Ctr, Rm 206,9415 Campus Point Dr, San Diego, CA 92093 USA. EM rayyagari@ucsd.edu FU Department of Ophthalmology, UCSD [NIH-P30EY22589]; NIH-NEI [EY002162]; Foundation Fighting Blindness; Research to Prevent Blindness; That Man May See, Inc.; Bernard A. Newcomb Macular Degeneration Research Fund; Hope for Vision; Scripps Research Institute [DK53505-12, U54 RR025204]; Beutler Foundation; [RO1EYO21237] FX This work was supported by RO1EYO21237 (RA), NIH-P30EY22589 (Department of Ophthalmology, UCSD), NIH-NEI EY002162 (JD), Foundation Fighting Blindness (RA, JD), Research to Prevent Blindness (RA, JD), That Man May See, Inc. (JD), The Bernard A. Newcomb Macular Degeneration Research Fund (JD), Hope for Vision (JD), The Scripps Research Institute (grants DK53505-12 and U54 RR025204 to PL), and The Beutler Foundation (PL). NR 16 TC 2 Z9 2 U1 1 U2 5 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 530 WALNUT STREET, STE 850, PHILADELPHIA, PA 19106 USA SN 1381-6810 EI 1744-5094 J9 OPHTHALMIC GENET JI Ophthalmic Genet. PD JAN 2 PY 2016 VL 37 IS 1 BP 44 EP 52 DI 10.3109/13816810.2014.929716 PG 9 WC Genetics & Heredity; Ophthalmology SC Genetics & Heredity; Ophthalmology GA DG2TP UT WOS:000371921400008 PM 25007332 ER PT J AU Bui, T Young, JW Frausto, RF Markello, TC Glasgow, B Aldave, AJ AF Bui, Tina Young, Jonathan W. Frausto, Ricardo F. Markello, Thomas C. Glasgow, Ben J. Aldave, Anthony J. TI Hereditary Benign Intraepithelial Dyskeratosis: Report of a Case and Re-examination of the Evidence for Locus Heterogeneity SO OPHTHALMIC GENETICS LA English DT Article DE Hereditary benign intraepithelial dyskeratosis; NLRP1; segment duplication ID INTRA-EPITHELIAL DYSKERATOSIS; CHROMOSOME 4Q35; MANIFESTATIONS; MUTATIONS; DYSTROPHY AB Background: Hereditary benign intraepithelial dyskeratosis (HBID) is a rare autosomal-dominant disorder of the conjunctiva and oral mucosa first described in and predominantly affecting descendents of Haliwa-Saponi Native Americans. We report a spontaneous case of histopathologically-confirmed HBID affecting an individual not of Native American ancestry.Materials and Methods: Report of a case with histopathologic examination of an excised conjunctival specimen as well as molecular and cytogenetic analysis.Results: A Caucasian boy with a history of oral lesions and conjunctival injection from birth developed bilateral corneal opacities at age 5 and underwent penetrating keratoplasty, with recurrence of the corneal opacification shortly after surgery. Examination of a conjunctival biopsy specimen revealed features consistent with HBID. Copy number variant (CNV) analysis revealed a de novo 4q35 duplication that overlapped the duplication previously associated with HBID, although no genes were identified in the common interval. NLRP1 gene sequencing failed to reveal a presumed pathogenic variant.Conclusions: HBID may develop de novo in individuals who are not of Native American ancestry. The absence of coding regions in a duplicated region of 4q35 common to both the individual that we report and previously associated with HBID raises questions regarding the significance of this CNV in the pathogenesis of HBID. C1 [Bui, Tina; Young, Jonathan W.; Frausto, Ricardo F.; Glasgow, Ben J.; Aldave, Anthony J.] Univ Calif Los Angeles, David Geffen Sch Med, Jules Stein Eye Inst, Los Angeles, CA 90095 USA. [Markello, Thomas C.] NIH, Undiagnosed Dis Program, Off Rare Dis, Bldg 10, Bethesda, MD 20892 USA. RP Aldave, AJ (reprint author), Univ Calif Los Angeles, Jules Stein Eye Inst, Ophthalmol, 100 Stein Plaza, Los Angeles, CA 90095 USA. EM aldave@jsei.ucla.edu FU National Eye Institute [1R01 EY022082, P30 EY000331]; Research to Prevent Blindness; NIH Interinstitute Common Fund, Office of the Director, NIH, Bethesda, Maryland FX Support provided by National Eye Institute grants 1R01 EY022082 (A.J.A.) and P30 EY000331 (core grant), and an unrestricted grant from Research to Prevent Blindness (A.J.A.). Funding for the Undiagnosed Diseases program is through the NIH Interinstitute Common Fund, Office of the Director, NIH, Bethesda, Maryland. NR 21 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 1381-6810 EI 1744-5094 J9 OPHTHALMIC GENET JI Ophthalmic Genet. PD JAN 2 PY 2016 VL 37 IS 1 BP 76 EP 80 DI 10.3109/13816810.2014.889169 PG 5 WC Genetics & Heredity; Ophthalmology SC Genetics & Heredity; Ophthalmology GA DG2TP UT WOS:000371921400012 PM 24555743 ER PT J AU Christen, WG Glynn, RJ Chew, EY Albert, CM Manson, JE AF Christen, William G. Glynn, Robert J. Chew, Emily Y. Albert, Christine M. Manson, JoAnn E. TI Folic Acid, Vitamin B-6, and Vitamin B-12 in Combination and Age-Related Cataract in a Randomized Trial of Women SO OPHTHALMIC EPIDEMIOLOGY LA English DT Article DE supplements; vitamin B-12; folic acid; Women's Antioxidant Folic Acid Cardiovascular Study; vitamin B-6; Cataract; randomized controlled trial ID NITRIC-OXIDE SYNTHASE; IMPROVES ENDOTHELIAL FUNCTION; NUCLEAR LENS OPACITIES; CHOROIDAL BLOOD-FLOW; BETA-CAROTENE; CIGARETTE-SMOKING; CLINICAL-TRIAL; CARDIOVASCULAR-DISEASE; MACULAR DEGENERATION; OXIDATIVE STRESS AB Purpose: To examine the incidence of cataract and cataract extraction in a trial of folic acid and vitamins B-6 and B-12. Methods: In a randomized, double-masked, placebo-controlled trial, 5442 female health professionals aged 40 years or older with preexisting cardiovascular disease (CVD) or three or more CVD risk factors were randomly assigned to receive a combination of folic acid (2.5 mg/day), vitamin B-6 (50 mg/day), and vitamin B-12 (1 mg/day), or placebo. A total of 3925 of these women did not have a diagnosis of cataract at baseline and were included in this analysis. The primary endpoint was age-related cataract, defined as an incident age-related lens opacity, responsible for a reduction in best-corrected visual acuity to 20/30 or worse, based on self-report confirmed by medical record review. Extraction of incident age-related cataract was a secondary endpoint of the trial. Results: During an average of 7.3 years of treatment and follow-up, 408 cataracts and 275 cataract extractions were documented. There were 215 cataracts in the combination treatment group and 193 in the placebo group (hazard ratio, HR, 1.10, 95% confidence interval, CI, 0.90-1.33; p = 0.36). For the secondary endpoint of cataract extraction, there were 155 in the combination treatment group and 120 in the placebo group (HR 1.28, 95% CI 1.01-1.63; p = 0.04). Conclusions: In this large-scale randomized trial of women at high risk of CVD, daily supplementation with a combination of folic acid, vitamin B-6, and vitamin B-12 had no significant effect on cataract, but may have increased the risk of cataract extraction. C1 [Christen, William G.; Glynn, Robert J.; Albert, Christine M.; Manson, JoAnn E.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Div Prevent Med,Dept Med, Boston, MA 02115 USA. [Glynn, Robert J.] Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA. [Chew, Emily Y.] NEI, Div Epidemiol & Clin Applicat, Bethesda, MD 20892 USA. [Albert, Christine M.] Harvard Univ, Brigham & Womens Hosp, Dept Med, Div Cardiovasc Med, Boston, MA 02115 USA. [Manson, JoAnn E.] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. RP Christen, WG (reprint author), Brigham & Womens Hosp, Dept Med, Div Prevent Med, 900 Commonwealth Ave East, Boston, MA 02215 USA. EM wchristen@rics.bwh.harvard.edu FU National Heart, Lung, and Blood Institute [HL46959]; National Eye Institute [EY06633] FX This study was supported by research grants HL46959 from the National Heart, Lung, and Blood Institute and EY06633 from the National Eye Institute. NR 62 TC 1 Z9 1 U1 0 U2 1 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 530 WALNUT STREET, STE 850, PHILADELPHIA, PA 19106 USA SN 0928-6586 EI 1744-5086 J9 OPHTHAL EPIDEMIOL JI Ophthalmic Epidemiol. PD JAN 2 PY 2016 VL 23 IS 1 BP 32 EP 39 DI 10.3109/09286586.2015.1130845 PG 8 WC Ophthalmology SC Ophthalmology GA DF3LF UT WOS:000371244800006 PM 26786311 ER PT J AU Dillman, AA Cookson, MR Galter, D AF Dillman, Allissa A. Cookson, Mark R. Galter, Dagmar TI ADAR2 affects mRNA coding sequence edits with only modest effects on gene expression or splicing in vivo SO RNA BIOLOGY LA English DT Article DE ADAR2; RNA-Seq; RNA editing ID GLOBAL REGULATION; BINDING DOMAIN; MOUSE; ENZYME; TRANSCRIPTOME; DSRNA AB Adenosine deaminases bind double stranded RNA and convert adenosine to inosine. Editing creates multiple isoforms of neurotransmitter receptors, such as with Gria2. Adar2 KO mice die of seizures shortly after birth, but if the Gria2 Q/R editing site is mutated to mimic the edited version then the animals are viable. We performed RNA-Seq on frontal cortices of Adar2(-/-) Gria2(R/R) mice and littermates. We found 56 editing sites with significantly diminished editing levels in Adar2 deficient animals with the majority in coding regions. Only two genes and 3 exons showed statistically significant differences in expression levels. This work illustrates that ADAR2 is important in site-specific changes of protein coding sequences but has relatively modest effects on gene expression and splicing in the adult mouse frontal cortex. C1 [Dillman, Allissa A.; Cookson, Mark R.] NIA, Cell Biol & Gene Express Sect, Neurogenet Lab, NIH, Bethesda, MD 20892 USA. [Dillman, Allissa A.; Galter, Dagmar] Karolinska Inst, Dept Neurosci, S-17177 Stockholm, Sweden. [Dillman, Allissa A.] NIH, Ctr Canc Res, Lab Receptor Biol & Gene Express, Bldg 10, Bethesda, MD 20892 USA. RP Galter, D (reprint author), Karolinska Inst, Dept Neurosci, S-17177 Stockholm, Sweden. EM Dagmar.Galter@ki.se FU Intramural Research Program of the NIH, National Institute on Aging [AG000947]; Swedish Research Council [2012-2353]; Swedish brain power FX This research was supported in part by the Intramural Research Program of the NIH, National Institute on Aging (Project number AG000947) and by the Swedish Research Council (Project 2012-2353) and Swedish brain power. This study used the high-performance computational capabilities of the Biowulf Linux cluster (http://biowulf.nih.gov). We are also very grateful to Dr. Peter Seeburg and Dr. Miyoko Higuchi for their kind gift of the ADAR2 knockout and control mouse brains required for this study. NR 25 TC 1 Z9 1 U1 1 U2 3 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 530 WALNUT STREET, STE 850, PHILADELPHIA, PA 19106 USA SN 1547-6286 EI 1555-8584 J9 RNA BIOL JI RNA Biol. PD JAN 2 PY 2016 VL 13 IS 1 BP 15 EP 24 DI 10.1080/15476286.2015.1110675 PG 10 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA DE9NA UT WOS:000370963300003 PM 26669816 ER PT J AU Dudekulay, DB Panda, AC Grammatikakis, I De, S Abdelmohsen, K Gorospe, M AF Dudekulay, Dawood B. Panda, Amaresh C. Grammatikakis, Ioannis De, Supriyo Abdelmohsen, Kotb Gorospe, Myriam TI CircInteractome: A web tool for exploring circular RNAs and their interacting proteins and microRNAs SO RNA BIOLOGY LA English DT Article DE CircRNA-miRNA; transcriptome; circRNA IRES; CLIP-Seq; divergent primer design; RNA-binding proteins; circRNA siRNA; sponge circRNAs ID POSTTRANSCRIPTIONAL GENE-REGULATION; BINDING PROTEINS; MESSENGER-RNA; EVOLUTIONARY CONSERVATION; TRANSLATION; EXPRESSION; DISEASE; CLIP; HUR; REVEALS AB Circular RNAs (circRNAs) are widely expressed in animal cells, but their biogenesis and functions are poorly understood. CircRNAs have been shown to act as sponges for miRNAs and may also potentially sponge RNA-binding proteins (RBPs) and are thus predicted to function as robust posttranscriptional regulators of gene expression. The joint analysis of large-scale transcriptome data coupled with computational analyses represents a powerful approach to elucidate possible biological roles of ribonucleoprotein (RNP) complexes. Here, we present a new web tool, CircInteractome (circRNA interactome), for mapping RBP- and miRNA-binding sites on human circRNAs. CircInteractome searches public circRNA, miRNA, and RBP databases to provide bioinformatic analyses of binding sites on circRNAs and additionally analyzes miRNA and RBP sites on junction and junction-flanking sequences. CircInteractome also allows the user the ability to (1) identify potential circRNAs which can act as RBP sponges, (2) design junction-spanning primers for specific detection of circRNAs of interest, (3) design siRNAs for circRNA silencing, and (4) identify potential internal ribosomal entry sites (IRES). In sum, the web tool CircInteractome, freely accessible at http://circinteractome.nia.nih.gov, facilitates the analysis of circRNAs and circRNP biology. C1 [Dudekulay, Dawood B.; Panda, Amaresh C.; Grammatikakis, Ioannis; De, Supriyo; Abdelmohsen, Kotb; Gorospe, Myriam] NIA, Genet Lab, Intramural Res Program, NIH, Baltimore, MD 21224 USA. RP Abdelmohsen, K (reprint author), NIA, Genet Lab, Intramural Res Program, NIH, Baltimore, MD 21224 USA. EM abdelmohsenk@mail.nih.gov OI Dudekula, Dawood/0000-0002-4054-1827; PANDA, AMARESH/0000-0003-3189-8995; De, Supriyo/0000-0002-2075-7655 FU National Institute on Aging Intramural Research Program of the National Institutes of Health FX This research was supported in full by the National Institute on Aging Intramural Research Program of the National Institutes of Health. NR 51 TC 12 Z9 12 U1 11 U2 27 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 530 WALNUT STREET, STE 850, PHILADELPHIA, PA 19106 USA SN 1547-6286 EI 1555-8584 J9 RNA BIOL JI RNA Biol. PD JAN 2 PY 2016 VL 13 IS 1 BP 34 EP 42 DI 10.1080/15476286.2015.1128065 PG 9 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA DE9NA UT WOS:000370963300005 PM 26669964 ER PT J AU Coghill, AE Shiels, MS Rycroft, RK Copeland, G Finch, JL Hakenewerth, AM Pawlish, KS Engels, EA AF Coghill, Anna E. Shiels, Meredith S. Rycroft, Randi K. Copeland, Glenn Finch, Jack L. Hakenewerth, Anne M. Pawlish, Karen S. Engels, Eric A. TI Rectal squamous cell carcinoma in immunosuppressed populations: is this a distinct entity from anal cancer? SO AIDS LA English DT Article DE HIV and cancer; HPV-associated cancer; rectal cancer; squamous cell carcinoma ID OF-THE-LITERATURE; HUMAN-PAPILLOMAVIRUS; UNITED-STATES; TRANSPLANT RECIPIENTS; HIV; RISK; AIDS; PEOPLE; COLON; METAANALYSIS AB Objective:Squamous cell carcinoma (SCC) of the rectum is rare, but as with anal cancer, risk may be increased among immunosuppressed individuals. We assessed risk of rectal SCC in HIV-infected people.Design:Population-based registry.Methods:We utilized the HIV/AIDS Cancer Match, a linkage of US HIV and cancer registries (1991-2010), to ascertain cases of anal SCC, rectal SCC, rectal non-SCC, and colon non-SCC. We compared risk in HIV-infected persons with the general population using standardized incidence ratios (SIRs) and evaluated risk factors using Poisson regression. We reviewed cancer registry case notes to confirm site and histology for a subset of cases.Results:HIV-infected persons had an excess risk of rectal SCC compared with the general population (SIR = 28.9; 95% CI 23.2-35.6), similar to the increase for anal SCC (SIR = 37.3). Excess rectal SCC risk was most pronounced among HIV-infected MSM (SIR = 61.2). Risk was not elevated for rectal non-SCC (SIR = 0.88) or colon non-SCC (SIR = 0.63). Individuals diagnosed with AIDS had higher rectal SCC rates than those with HIV-only (incidence rate ratio = 1.92; 95% CI 1.08-3.42). Based on available information, one-third of rectal SCCs were determined to be misclassified anal cancer.Conclusion:HIV-infected individuals, especially with advanced immunosuppression, appear to have substantially elevated risk for rectal SCC. As for anal SCC, rectal SCC risk was highest in MSM, pointing to involvement of a sexually transmitted infection such as human papillomavirus. Site misclassification was present, and detailed information on tumour location is needed to prove that rectal SCC is a distinct entity. Copyright (C) 2015 Wolters Kluwer Health, Inc. All rights reserved. C1 [Coghill, Anna E.; Shiels, Meredith S.; Engels, Eric A.] NCI, Div Canc Epidemiol & Genet, Rockville, MD 20892 USA. [Rycroft, Randi K.; Finch, Jack L.] Colorado Dept Publ Hlth & Environm, Colorado Cent Canc Registry, Denver, CO USA. [Copeland, Glenn] Michigan Stage Canc Registry, Michigan Canc Surveillance Program, Trenton, NJ USA. [Hakenewerth, Anne M.] North Carolina Div Publ Hlth, Communicable Dis Branch, Trenton, NJ USA. [Pawlish, Karen S.] New Jersey Dept Hlth, New Jersey State Canc Registry, Trenton, NJ USA. RP Coghill, AE (reprint author), NCI, 9609 Med Ctr Dr, Rockville, MD 20892 USA. EM anna.coghill@nih.gov FU Intramural Research Program of the National Cancer Institute; SEER Program of the National Cancer Institute: Connecticut [HHSN261201000024C]; SEER 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 [5U58DP003921-03]; 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; HIV Incidence and Case Surveillance Branch of the Centers for Disease Control and Prevention, National HIV Surveillance Systems: Colorado; HIV Incidence and Case Surveillance Branch of the Centers for Disease Control and Prevention, National HIV Surveillance Systems: Connecticut [5U62PS001005-05]; HIV Incidence and Case Surveillance Branch of the Centers for Disease Control and Prevention, National HIV Surveillance Systems: Michigan [U62PS004011-02]; HIV Incidence and Case Surveillance Branch of the Centers for Disease Control and Prevention, National HIV Surveillance Systems: New Jersey [U62PS0040 01-2] FX The views expressed in this article are those of the authors and should not be interpreted to reflect the views or policies of the National Cancer Institute, HIV/AIDS or cancer registries, or their contractors. This research was supported in part by the Intramural Research Program of the National Cancer Institute.; The following cancer registries were supported by the SEER 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 (5U58DP003921-03), New Jersey (5U58/ DP003931-02), and Texas (5U58DP000824-04). The New Jersey State Cancer Registry was also supported by the state of New Jersey. The following HIV registries were supported by HIV Incidence and Case Surveillance Branch of the Centers for Disease Control and Prevention, National HIV Surveillance Systems: Colorado, Connecticut (5U62PS001005-05), Michigan (U62PS004011-02), and New Jersey (U62PS0040 01-2). NR 27 TC 0 Z9 0 U1 1 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 0269-9370 EI 1473-5571 J9 AIDS JI Aids PD JAN 2 PY 2016 VL 30 IS 1 BP 105 EP 112 DI 10.1097/QAD.0000000000000873 PG 8 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA DC6EU UT WOS:000369313400001 PM 26372482 ER PT J AU Kelen, GD Hsieh, YH Rothman, RE Patel, EU Laeyendecker, OB Marzinke, MA Clarke, W Parsons, T Manucci, JL Quinn, TC AF Kelen, Gabor D. Hsieh, Yu-Hsiang Rothman, Richard E. Patel, Eshan U. Laeyendecker, Oliver B. Marzinke, Mark A. Clarke, William Parsons, Teresa Manucci, Jordyn L. Quinn, Thomas C. TI Improvements in the continuum of HIV care in an inner-city emergency department SO AIDS LA English DT Article DE cascade of care; emergency department; HIV; HIV testing program; seroprevalence studies ID HUMAN-IMMUNODEFICIENCY-VIRUS; UNITED-STATES; SCREENING-PROGRAMS; VIRAL SUPPRESSION; INFECTION; RISK; ENGAGEMENT; PREVENTION; EXPERIENCE; EXCHANGE AB Objective:The Johns Hopkins Hospital Emergency Department has served as a window on the HIV epidemic for 25 years, and as a pioneer in emergency department-based screening/linkage-to-care (LTC) programs. We document changes in the burden of HIV and HIV care metrics to the evolving HIV epidemic in inner-city Baltimore.Design/methods:We analyzed seven serosurveys conducted on 18144 adult Johns Hopkins Hospital Emergency Department patients between 1987 and 2013 as well as our HIV-screening/LTC program (2007, 2013) for trends in HIV prevalence, cross-sectional annual incidence estimates, undiagnosed HIV, LTC, antiretrovirals treatment, and viral suppression.Results:HIV prevalence in 1987 was 5.2%, peaked at more than 11% from 1992 to 2003 and declined to 5.6% in 2013. Seroprevalence was highest for black men (initial 8.0%, peak 20.0%, last 9.9%) and lowest for white women. Among HIV-positive individuals, proportion of undiagnosed infection was 77% in 1987, 28% in 1992, and 12% by 2013 (P<0.001). Cross-sectional annual HIV incidence estimates declined from 2.28% in 2001 to 0.16% in 2013. Thirty-day LTC improved from 32% (2007) to 72% (2013). In 2013, 80% of HIV-positive individuals had antiretrovirals ARVs detected in sera, markedly increased from 2007 (27%) (P<0.001). Proportion of HIV-positive individuals with viral suppression (<400copies/ml) increased from 23% (2001) to 59% (2013) (P<0.001).Conclusion:Emergency department-based HIV testing has evolved from describing the local epidemic to a strategic interventional role, serving as a model for early HIV detection and LTC. Our contribution to community-based HIV-screening and LTC program parallels declines in undiagnosed HIV infection and incidence, and increases in antiretroviral use with associated viral suppression in the community. Copyright (C) 2015 Wolters Kluwer Health, Inc. All rights reserved. C1 [Kelen, Gabor D.; Hsieh, Yu-Hsiang; Rothman, Richard E.] Johns Hopkins Univ, Sch Med, Dept Emergency Med, Suite 6-100,1830 E Monument St, Baltimore, MD 21287 USA. [Patel, Eshan U.; Laeyendecker, Oliver B.; Quinn, Thomas C.] NIAID, Div Intramural Res, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA. [Marzinke, Mark A.; Clarke, William] Johns Hopkins Univ, Sch Med, Dept Pathol, Baltimore, MD 21287 USA. [Marzinke, Mark A.; Parsons, Teresa; Manucci, Jordyn L.; Quinn, Thomas C.] Johns Hopkins Univ, Sch Med, Dept Med, Baltimore, MD 21287 USA. RP Kelen, GD (reprint author), Johns Hopkins Univ, Sch Med, Dept Emergency Med, Suite 6-100,1830 E Monument St, Baltimore, MD 21287 USA. EM gkelen@jhmi.edu OI Kelen, Gabor/0000-0002-3236-8286; Rothman, Richard/0000-0002-1017-9505; Patel, Eshan/0000-0003-2174-5004 FU Division of Intramural Research, National Institute of Allergy and Infectious Diseases at National Institutes of Health; Maryland Department of Health and Mental Hygiene; Baltimore City Health Department; Gilead Foundation HIV Focus Program; Emergency Medicine Foundation; National Institute of Allergy and Infectious Diseases at National Institutes of Health [K01AI100681] FX This work was supported by Division of Intramural Research, National Institute of Allergy and Infectious Diseases at National Institutes of Health; Maryland Department of Health and Mental Hygiene; Baltimore City Health Department; the Gilead Foundation HIV Focus Program; the Emergency Medicine Foundation; and National Institute of Allergy and Infectious Diseases at National Institutes of Health [K01AI100681 to Y-HH]. NR 48 TC 3 Z9 3 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 0269-9370 EI 1473-5571 J9 AIDS JI Aids PD JAN 2 PY 2016 VL 30 IS 1 BP 113 EP 120 DI 10.1097/QAD.0000000000000896 PG 8 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA DC6EU UT WOS:000369313400002 PM 26731757 ER PT J AU Williams, PL Hazra, R Van Dyke, RB Yildirim, C Crain, MJ Seage, GR Civitello, L Ellis, A Butler, L Rich, K AF Williams, Paige L. Hazra, Rohan Van Dyke, Russell B. Yildirim, Cenk Crain, Marilyn J. Seage, George R., III Civitello, Lucy Ellis, Angela Butler, Laurie Rich, Kenneth CA Pediat HIV AIDS Cohort Study TI Antiretroviral exposure during pregnancy and adverse outcomes in HIV-exposed uninfected infants and children using a trigger-based design SO AIDS LA English DT Article DE antiretroviral; HIV-exposed; infants; mitochondrial dysfunction; safety ID HUMAN-IMMUNODEFICIENCY-VIRUS; PERSISTENT MITOCHONDRIAL DYSFUNCTION; IN-UTERO; INFECTED WOMEN; PERINATAL EXPOSURE; UNITED-STATES; TRANSMISSION; SAFETY; TOXICITY; THERAPY AB Objective:To evaluate the safety of in-utero antiretroviral exposure in children born to mothers with HIV, using a trigger-based design.Design:The Surveillance Monitoring of ART Toxicities Study is a prospective cohort study conducted at 22 US sites to evaluate safety of in-utero antiretroviral drug exposure in HIV-uninfected children born to HIV-infected mothers. Children meeting predefined clinical or laboratory thresholds have more intensive evaluations to determine whether they meet criteria for adverse events.Methods:Adverse event cases were defined for the following domains: growth, hearing, language, neurology, neurodevelopment, metabolic, hematologic/clinical chemistry and blood lactate. We used adjusted log-binomial models to calculate relative risks (RR) of case status overall and within individual domains for various antiretroviral exposures during pregnancy.Results:Among 2680 youth enrolled between 2007 and 2012 (48% female, 66% black, 33% Hispanic), 48% met a trigger and 25% were defined as a case in at least one domain. Language (13.2%) and metabolic (11.4%) cases were most common. After adjustment for birth cohort and other factors, there was no association of any antiretroviral regimen, drug class, or individual drug with meeting overall case criteria (case in any domain). Within individual domains, zidovudine (74% exposed) was associated with increased risk of metabolic case [RR=1.69, 95%confidence interval (CI) 1.08-2.64] and didanosine plus stavudine (<1% exposed) with increased risk of both neurodevelopmental (RR=12.40, 95%CI 5.29-29.08) and language (RR=4.84, 95%CI 1.14-20.51) cases.Conclusion:Our findings support current recommendations for combination antiretroviral therapy during pregnancy, although higher risk of metabolic disorder with zidovudine exposure warrants further study. Copyright (C) 2015 Wolters Kluwer Health, Inc. All rights reserved. C1 [Williams, Paige L.; Yildirim, Cenk; Seage, George R., III] Harvard Univ, TH Chan Sch Publ Hlth, Ctr Biostat AIDS Res, Boston, MA 02115 USA. [Williams, Paige L.] Harvard Univ, TH Chan Sch Publ Hlth, Dept Biostat, 655 Huntington Ave,415 Bldg I, Boston, MA 02115 USA. [Hazra, Rohan] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Bethesda, MD USA. [Van Dyke, Russell B.] Tulane Univ, Sch Med, 1430 Tulane Ave, New Orleans, LA 70112 USA. [Crain, Marilyn J.] Univ Alabama Birmingham, Dept Pediat, Birmingham, AL USA. [Crain, Marilyn J.] Univ Alabama Birmingham, Dept Microbiol, Birmingham, AL 35294 USA. [Williams, Paige L.; Seage, George R., III] Harvard Univ, TH Chan Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. [Civitello, Lucy] Childrens Natl Med Ctr, Washington, DC 20010 USA. [Ellis, Angela; Butler, Laurie] Frontier Sci Technol & Res Fdn, Amherst, NY USA. [Rich, Kenneth] Univ Illinois, Chicago, IL USA. RP Williams, PL (reprint author), Harvard Univ, TH Chan Sch Publ Hlth, Dept Biostat, 655 Huntington Ave,415 Bldg I, Boston, MA 02115 USA. EM paige@sdac.harvard.edu FU Eunice Kennedy Shriver National Institute of Child Health and Human Development; National Institute on Drug Abuse; National Institute of Allergy and Infectious Diseases; Office of AIDS Research; National Institute of Mental Health; National Institute of Neurological Disorders and Stroke; National Institute on Deafness and Other Communication Disorders; National Heart Lung and Blood Institute; National Institute of Dental and Craniofacial Research; National Institute on Alcohol Abuse and Alcoholism; Harvard T.H. Chan School of Public Health [HD052102]; Tulane University School of Medicine [HD052104] FX The Pediatric HIV/AIDS Cohort Study (PHACS) was supported by the Eunice Kennedy Shriver National Institute of Child Health and Human Development with co-funding from the National Institute on Drug Abuse, the National Institute of Allergy and Infectious Diseases, the Office of AIDS Research, the National Institute of Mental Health, the National Institute of Neurological Disorders and Stroke, the National Institute on Deafness and Other Communication Disorders, the National Heart Lung and Blood Institute, the National Institute of Dental and Craniofacial Research, and the National Institute on Alcohol Abuse and Alcoholism, through cooperative agreements with the Harvard T.H. Chan School of Public Health(HD052102) and the Tulane University School of Medicine (HD052104). NR 39 TC 6 Z9 6 U1 2 U2 9 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 0269-9370 EI 1473-5571 J9 AIDS JI Aids PD JAN 2 PY 2016 VL 30 IS 1 BP 133 EP 144 DI 10.1097/QAD.0000000000000916 PG 12 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA DC6EU UT WOS:000369313400004 PM 26731758 ER PT J AU Miljkovic, MD Grossman, SA Ye, XB Ellsworth, S Terezakis, S AF Miljkovic, Milos D. Grossman, Stuart A. Ye, Xiaobu Ellsworth, Susannah Terezakis, Stephanie TI Patterns of Radiation-Associated Lymphopenia in Children with Cancer SO CANCER INVESTIGATION LA English DT Article DE Brain tumors; Sarcomas; Radiation therapy; Lymphopenia ID ACUTE LYMPHOBLASTIC-LEUKEMIA; EARLY LYMPHOCYTE RECOVERY; PROGNOSTIC INDICATOR; RISK; INFILTRATION; SURVIVAL; CHEMOTHERAPY; RADIOTHERAPY; IRRADIATION; INVOLUTION AB Adults with cancer commonly develop severe lymphopenia two months following chemoradiation therapy, which is an independent predictor of survival. In this retrospective study of 53 children with central nervous system tumors and sarcomas, the frequency, severity, and duration of radiation-associated lymphopenia was similar to that seen in adults. Pretreatment lymphocyte counts were 1,000 cells/mm(3) or greater in all patients, with 66% experiencing grade III-IV lymphopenia two months after chemoradiation. Lymphocyte counts remained significantly lower than baseline 12 months later. Further studies are needed to determine if this is also associated with poorer survival, as seen in adults. C1 [Miljkovic, Milos D.] NCI, Med Oncol Serv, Bethesda, MD 20892 USA. [Grossman, Stuart A.; Ye, Xiaobu] Johns Hopkins, Sidney Kimmel Comprehens Canc Ctr, Dept Med Oncol, Baltimore, MD 21231 USA. [Ellsworth, Susannah; Terezakis, Stephanie] Johns Hopkins, Sidney Kimmel Comprehens Canc Ctr, Dept Radiat Oncol, Baltimore, MD 21231 USA. RP Terezakis, S (reprint author), Johns Hopkins, Sidney Kimmel Comprehens Canc Ctr, Radiat Oncol, 401 N Broadway St, Baltimore, MD 21231 USA. EM sterezak@jhmi.edu RI Miljkovic, Milos/F-7685-2011; OI Miljkovic, Milos/0000-0001-5848-6320; Terezakis, Stephanie/0000-0003-4933-6712 FU NCI NIH HHS [P30 CA006973] NR 28 TC 0 Z9 0 U1 0 U2 1 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 530 WALNUT STREET, STE 850, PHILADELPHIA, PA 19106 USA SN 0735-7907 EI 1532-4192 J9 CANCER INVEST JI Cancer Invest. PD JAN 2 PY 2016 VL 34 IS 1 BP 32 EP 38 DI 10.3109/07357907.2015.1086366 PG 7 WC Oncology SC Oncology GA DC8XY UT WOS:000369504700005 PM 26745229 ER PT J AU Lujan, SA Williams, JS Kunkel, TA AF Lujan, Scott A. Williams, Jessica S. Kunkel, Thomas A. TI Eukaryotic genome instability in light of asymmetric DNA replication SO CRITICAL REVIEWS IN BIOCHEMISTRY AND MOLECULAR BIOLOGY LA English DT Review DE DNA mismatch repair; exonucleolytic proofreading; genomic ribonucleotide; mutation; polymerase; replication fork ID LEADING-STRAND DNA; UNIQUE ERROR SIGNATURE; MISMATCH-REPAIR; POLYMERASE-EPSILON; SACCHAROMYCES-CEREVISIAE; RIBONUCLEOTIDE INCORPORATION; ESCHERICHIA-COLI; HIGH-FIDELITY; CATALYTIC DOMAINS; TOPOISOMERASE-I AB The eukaryotic nuclear genome is replicated asymmetrically, with the leading strand replicated continuously and the lagging strand replicated as discontinuous Okazaki fragments that are subsequently joined. Both strands are replicated with high fidelity, but the processes used to achieve high fidelity are likely to differ. Here we review recent studies of similarities and differences in the fidelity with which the three major eukaryotic replicases, DNA polymerases , , and , replicate the leading and lagging strands with high nucleotide selectivity and efficient proofreading. We then relate the asymmetric fidelity at the replication fork to the efficiency of DNA mismatch repair, ribonucleotide excision repair and topoisomerase 1 activity. C1 [Lujan, Scott A.; Williams, Jessica S.; Kunkel, Thomas A.] NIEHS, Genome Integr & Struct Biol Lab, POB 12233, Res Triangle Pk, NC 27709 USA. RP Kunkel, TA (reprint author), NIEHS, Genome Integr & Struct Biol Lab, POB 12233, Res Triangle Pk, NC 27709 USA. EM kunkel@niehs.nih.gov FU Division of Intramural Research of the NIH, NIEHS [Z01 ES065070] FX This work was supported by Project Z01 ES065070 to T.A.K. from the Division of Intramural Research of the NIH, NIEHS. NR 96 TC 1 Z9 1 U1 5 U2 17 PU TAYLOR & FRANCIS LTD PI ABINGDON PA 2-4 PARK SQUARE, MILTON PARK, ABINGDON OR14 4RN, OXON, ENGLAND SN 1040-9238 EI 1549-7798 J9 CRIT REV BIOCHEM MOL JI Crit. Rev. Biochem. Mol. Biol. PD JAN 2 PY 2016 VL 51 IS 1 BP 43 EP 52 DI 10.3109/10409238.2015.1117055 PG 10 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA DD2RG UT WOS:000369769300005 PM 26822554 ER PT J AU Liang, S Bian, XM Liang, D Sivils, JC Neckers, LM Cox, MB Xie, H AF Liang, Su Bian, Xiaomei Liang, Dong Sivils, Jeffrey C. Neckers, Leonard M. Cox, Marc B. Xie, Huan TI Solution formulation development and efficacy of MJC13 in a preclinical model of castration-resistant prostate cancer SO PHARMACEUTICAL DEVELOPMENT AND TECHNOLOGY LA English DT Article DE Androgen-independent; castration-resistant prostate cancer; efficacy; formulation; MJC13; preformulation ID ANDROGEN RECEPTOR; INHIBITION; FKBP52; EXPRESSION; BINDING; CELLS AB MJC13, a novel FKBP52 targeting agent, has potential use for the treatment of castration-resistant prostate cancer. The purpose of this work was to develop a solution formulation of MJC13, and obtain its efficacy profile in a human prostate cancer xenograft mouse model. Preformulation studies were conducted to evaluate the physicochemical properties. Co-solvent systems were evaluated for aqueous solubility and tolerance. A human prostate cancer xenograft mouse model was established by growing 22Rv1 prostate cancer cells in C.B-17 SCID mice. The optimal formulation was used to study the efficacy of MJC13 in this preclinical model of castrate-resistant prostate cancer. We found that MJC13 was stable (at least for 1 month), highly lipophilic (logP=6.49), poorly soluble in water (0.28 mu g/mL), and highly plasma protein bound (>98%). The optimal formulation consisting of PEG 400 and Tween 80 (1:1, v/v) allowed us to achieve a MJC13 concentration of 7.5mg/mL, and tolerated an aqueous environment. After twice weekly intratumoral injection with 10mg/kg MJC13 in this formulation for four consecutive weeks, tumor volumes were significantly reduced compared to vehicle-treated controls. C1 [Liang, Su; Bian, Xiaomei; Liang, Dong; Xie, Huan] Texas So Univ, Coll Pharm & Hlth Sci, Dept Pharmaceut Sci, 3100 Cleburne St,Gray Hall 119, Houston, TX 77004 USA. [Sivils, Jeffrey C.; Cox, Marc B.] Univ Texas El Paso, Border Biomed Res Ctr, Dept Biol Sci, El Paso, TX 79968 USA. [Neckers, Leonard M.] NCI, Urol Oncol Branch, Bethesda, MD 20892 USA. RP Xie, H (reprint author), Texas So Univ, Coll Pharm & Hlth Sci, Dept Pharmaceut Sci, 3100 Cleburne St,Gray Hall 119, Houston, TX 77004 USA. EM xieh@tsu.edu FU NIH/RTRN [5U54RR022762]; NIH/NIGMS [1SC3GM102018-01, SC1GM084863]; NIH/NIMHD/RCMI [2G12MD007605-22A1, G12MD007592]; NIH/NCRR/RCMI [5G12RR008124]; State of Texas CPRIT [RP110444-P2] FX HX has research grant support from an NIH/RTRN grant (5U54RR022762-05), NIH/NIGMS grant (1SC3GM102018-01) and from NIH/NIMHD/RCMI grant (2G12MD007605-22A1). MBC has research grant support from NIH/NCRR/RCMI grant (5G12RR008124), NIH/NIMHD/RCMI grant (G12MD007592), NIH/NIGMS grant (SC1GM084863) and State of Texas CPRIT grant (RP110444-P2). NR 24 TC 3 Z9 3 U1 1 U2 3 PU TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXON, ENGLAND SN 1083-7450 EI 1097-9867 J9 PHARM DEV TECHNOL JI Pharm. Dev. Technol. PD JAN 2 PY 2016 VL 21 IS 1 BP 121 EP 126 DI 10.3109/10837450.2014.979946 PG 6 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA DB7LR UT WOS:000368697300015 PM 25380396 ER PT J AU Sayers, BC Walker, NJ Roycroft, JH Germolec, DR Baker, GL Clark, ML Hayden, BK DeFord, H Dill, JA Gupta, A Stout, MD AF Sayers, Brian C. Walker, Nigel J. Roycroft, Joseph H. Germolec, Dori R. Baker, Gregory L. Clark, Mark L. Hayden, Barry K. DeFord, Henry Dill, Jeffrey A. Gupta, Amit Stout, Matthew D. TI Lung deposition and clearance of microparticle and nanoparticle C-60 fullerene aggregates in B6C3F1 mice and Wistar Han rats following nose-only inhalation for 13 weeks SO TOXICOLOGY LA English DT Article DE C-60 fullerene; Nanoparticle; Inhalation; Lung deposition; Lung clearance ID INCREASED PULMONARY TOXICITY; ULTRAFINE PARTICLES; TRANSLOCATION; EXPOSURE; MECHANISMS; OVERLOAD AB C-60 fullerenes (C-60) are spherical structures consisting of 60 carbon atoms that are generated via combustion from both natural and anthropogenic sources. C-60 are also synthesized intentionally for industrial applications. Individual C-60 structures have an approximate diameter of 1 nm; however, C-60 readily forms aggregates and typically exist as larger particles that range from nanometers to micrometers in diameter. In this report, lung and extrapulmonary tissue deposition and lung clearance of C-60 nanoparticles (nano-C-60, 50 nm) and microparticles (micro-C-60, 1 mu m) were examined in Wistar Han rats and B6C3F1/N mice after nose-only inhalation for 90 days. Exposure concentrations were 0.5 and 2 mg/m(3) (nano-C-60) and 2,15, and 30 mg/m(3) (micro-C-60). For both C-60 particle sizes, the C-60 lung burden increased proportionally to exposure concentration. The C-60 lung burden was greater in both species at all time points following exposure to nano-C-60 particle exposure compared to micro-C-60 exposure at the common exposure concentration 2 mg/m(3). The calculated C-60 particle lung retention half-times were similar for both nano-C-60 and micro-C-60 exposure at 2 mg/m(3) in male mice (15-16 days). In contrast, in male rats, the half-time of C-60 particles following nano-C-60 exposure (61 days) was roughly twice as long as the half-time following micro-C-60 exposure (27 days) at the same exposure concentration (2 mg/m(3)) and was similar to the clearance following micro-C-60 exposure at higher exposure concentrations (15 and 30 mg/m(3)). C-60 was detected in bronchial lymph nodes but the burden was not quantified due to the high variability in the data. C-60 concentrations were below the experimental limit of quantitation (ELOQ) in liver, spleen, blood, brain and kidney tissues. These tissue burden data provide information for comparison between nanometer and micrometer sized C-60 particle exposure and will aid in the interpretation of toxicity data. Published by Elsevier Ireland Ltd. C1 [Sayers, Brian C.; Walker, Nigel J.; Roycroft, Joseph H.; Germolec, Dori R.; Stout, Matthew D.] NIEHS, Div Natl Toxicol Program, 111 Alexander Dr,POB 12233, Res Triangle Pk, NC 27709 USA. [Baker, Gregory L.; Clark, Mark L.; Hayden, Barry K.; DeFord, Henry; Dill, Jeffrey A.; Gupta, Amit] Battelle Toxicol Northwest, 900 Battelle Blvd, Richland, WA 99354 USA. RP Stout, MD (reprint author), NIEHS, Div Natl Toxicol Program, 111 Alexander Dr,POB 12233, Res Triangle Pk, NC 27709 USA. EM stoutm@niehs.nih.gov RI Walker, Nigel/D-6583-2012 OI Walker, Nigel/0000-0002-9111-6855 FU NIH, National Institute of Environmental Health Sciences (NIEHS); NTP [N01-ES-55538, N01-ES-5553] FX The authors also thank Drs. Suramya Waidynatha and William Gwinn for their thoughtful and critical review of this manuscript. This work was supported [in part] by the NIH, National Institute of Environmental Health Sciences (NIEHS) and by NTP Contracts N01-ES-55538 and N01-ES-5553. NR 25 TC 1 Z9 1 U1 6 U2 22 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0300-483X J9 TOXICOLOGY JI Toxicology PD JAN 2 PY 2016 VL 339 BP 87 EP 96 DI 10.1016/j.tox.2015.11.003 PG 10 WC Pharmacology & Pharmacy; Toxicology SC Pharmacology & Pharmacy; Toxicology GA DC1CG UT WOS:000368953800009 PM 26612504 ER PT J AU Vuong, C Yeh, AJ Cheung, GYC Otto, M AF Cuong Vuong Yeh, Anthony J. Cheung, Gordon Y. C. Otto, Michael TI Investigational drugs to treat methicillin-resistant Staphylococcus aureus SO EXPERT OPINION ON INVESTIGATIONAL DRUGS LA English DT Review DE antibiotics; antibiotic resistance; quorum-sensing blockers; Staphylococcus aureus; therapeutics; therapeutic antibodies; vaccine ID SURFACE DETERMINANT B; HUMAN MONOCLONAL-ANTIBODY; CLUMPING FACTOR-A; PENICILLIN-BINDING PROTEINS; PANTON-VALENTINE LEUKOCIDIN; POLY-N-ACETYLGLUCOSAMINE; ACTIVITY IN-VITRO; ALPHA-TOXIN; CAPSULAR POLYSACCHARIDE; ENTEROTOXIN-B AB Introduction:Staphylococcus aureus remains one of the leading causes of morbidity and mortality worldwide. This is to a large extent due to antibiotic-resistant strains, in particular methicillin-resistant S. aureus (MRSA). While the toll of invasive MRSA infections appears to decrease in U.S. hospitals, the rate of community-associated MRSA infections remains constant and there is a surge of MRSA in many other countries, a situation that calls for continuing if not increased efforts to find novel strategies to combat MRSA infections.Areas covered: This review provides an overview of current investigational drugs and therapeutic antibodies against S. aureus in early clinical development (up to phase II clinical development). It includes a short description of the mechanism of action and a presentation of microbiological and clinical data.Expert opinion: Increased recent antibiotic development efforts and results from pathogenesis research have led to several new antibiotics and therapies, such as anti-virulence drugs, as well as a more informed selection of targets for vaccination efforts against MRSA. This developing portfolio of novel anti-staphylococcal drugs will hopefully provide us with additional and more efficient ways to combat MRSA infections in the near future and prevent us from running out of treatment options, even if new resistances arise. C1 [Cuong Vuong] AiCuris GmbH & Co KG, D-42117 Wuppertal, Germany. [Yeh, Anthony J.] NIAID, Bacteriol Lab, NIH, Bethesda, MD 20892 USA. [Cheung, Gordon Y. C.; Otto, Michael] NIAID, NIH, Bacteriol Lab, Bethesda, MD 20892 USA. RP Otto, M (reprint author), NIAID, NIH, Bacteriol Lab, Bldg 33,1W10,9000 Rockville Pike, Bethesda, MD 20892 USA. EM motto@niaid.nih.gov OI Otto, Michael/0000-0002-2222-4115 FU Intramural Research Program of the National Institute of Allergy and Infectious Diseases (NIAID), The National Institutes of Health (NIH); NIAID FX This work was supported by the Intramural Research Program of the National Institute of Allergy and Infectious Diseases (NIAID), The National Institutes of Health (NIH). C Vuong is an employee of Aicuris GmbH & Co. KG; M. Otto and GYC Cheung are employees of the NIAID. AJ Yeh has a post baccalaureate fellowship from the NIAID. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed. NR 163 TC 3 Z9 3 U1 9 U2 45 PU TAYLOR & FRANCIS LTD PI ABINGDON PA 2-4 PARK SQUARE, MILTON PARK, ABINGDON OR14 4RN, OXON, ENGLAND SN 1354-3784 EI 1744-7658 J9 EXPERT OPIN INV DRUG JI Expert Opin. Investig. Drugs PD JAN 2 PY 2016 VL 25 IS 1 BP 73 EP 93 DI 10.1517/13543784.2016.1109077 PG 21 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA DA7ZE UT WOS:000368023300003 PM 26536498 ER PT J AU Brown, RJ Chan, JL Jaffe, ES Cochran, E DePaoli, AM Gautier, JF Goujard, C Vigouroux, C Gorden, P AF Brown, Rebecca J. Chan, Jean L. Jaffe, Elaine S. Cochran, Elaine DePaoli, Alex M. Gautier, Jean-Francois Goujard, Cecile Vigouroux, Corinne Gorden, Phillip TI Lymphoma in acquired generalized lipodystrophy SO LEUKEMIA & LYMPHOMA LA English DT Article DE Acquired generalized lipodystrophy; leptin; metreleptin; mycosis fungoides; T-cell lymphoma ID LEPTIN-REPLACEMENT THERAPY; AUTOIMMUNE; DISORDERS; EFFICACY AB Acquired generalized lipodystrophy (AGL) is a rare disease thought to result from autoimmune destruction of adipose tissue. Peripheral T-cell lymphoma (PTCL) has been reported in two AGL patients. We report five additional cases of lymphoma in AGL, and analyze the role of underlying autoimmunity and recombinant human leptin (metreleptin) replacement in lymphoma development. Three patients developed lymphoma during metreleptin treatment (two PTCL and one ALK-positive anaplastic large cell lymphoma), and two developed lymphomas (mycosis fungoides and Burkitt lymphoma) without metreleptin. AGL is associated with high risk for lymphoma, especially PTCL. Autoimmunity likely contributes to this risk. Lymphoma developed with or without metreleptin, suggesting metreleptin does not directly cause lymphoma development; a theoretical role of metreleptin in lymphoma progression remains possible. For most patients with AGL and severe metabolic complications, the proven benefits of metreleptin on metabolic disease will likely outweigh theoretical risks of metreleptin in lymphoma development or progression. C1 [Brown, Rebecca J.; Cochran, Elaine; Gorden, Phillip] NIDDK, Diabet Endocrinol & Obes Branch, NIH, Bethesda, MD 20892 USA. [Chan, Jean L.] Bristol Myers Squibb Co, San Diego, CA USA. [Jaffe, Elaine S.] NCI, Hematopathol Sect, Pathol Lab, Ctr Canc Res,NIH, Bethesda, MD 20892 USA. [DePaoli, Alex M.] William Sansum Diabet Ctr, Santa Barbara, CA USA. [Gautier, Jean-Francois] Univ Paris 07, Lariboisiere Hosp, AP HP, Dept Diabet & Endocrinol,DHU FIRE, Paris, France. [Goujard, Cecile] Hop Bicetre, AP HP, Le Kremlin Bicetre, France. [Goujard, Cecile] INSERM, CESP U1018, F-94275 Le Kremlin Bicetre, France. [Goujard, Cecile] Fac Med Paris Sud, Le Kremlin Bicetre, France. [Vigouroux, Corinne] Fac Med Pierre & Marie Curie, Ctr Rech St Antoine, INSERM, UMR S938, F-75012 Paris, France. [Vigouroux, Corinne] Univ Paris 06, Sorbonne Univ, UMR S938, F-75005 Paris, France. [Vigouroux, Corinne] ICAN, Inst Cardiometab & Nutr, F-75013 Paris, France. [Vigouroux, Corinne] Hop St Antoine, AP HP, Lab Commun Biol & Genet Mol, F-75012 Paris, France. RP Brown, RJ (reprint author), Bldg 10-CRC,Room 6-5940,10 Ctr Dr,MSC 1612, Bethesda, MD 20892 USA. EM brownrebecca@mail.nih.gov FU National Institute of Diabetes and Digestive and Kidney Diseases; National Cancer Institute; Assistance Publique-Hopitaux de Paris; Inserm FX This work was supported by the intramural research programs of the National Institute of Diabetes and Digestive and Kidney Diseases (RJB, EC, PG) and the National Cancer Institute (ESJ), and by Assistance Publique-Hopitaux de Paris and Inserm (JFG, CG and CV). NR 26 TC 3 Z9 3 U1 0 U2 3 PU TAYLOR & FRANCIS LTD PI ABINGDON PA 2-4 PARK SQUARE, MILTON PARK, ABINGDON OR14 4RN, OXON, ENGLAND SN 1042-8194 EI 1029-2403 J9 LEUKEMIA LYMPHOMA JI Leuk. Lymphoma PD JAN 2 PY 2016 VL 57 IS 1 BP 45 EP 50 DI 10.3109/10428194.2015.1040015 PG 6 WC Oncology; Hematology SC Oncology; Hematology GA DA8AC UT WOS:000368025700011 PM 25864863 ER PT J AU Bradford, D Reilly, KM Widemann, BC Sandler, A Kummar, S AF Bradford, Diana Reilly, Karlyne M. Widemann, Brigitte C. Sandler, Abby Kummar, Shivaani TI Developing therapies for rare tumors: opportunities, challenges and progress SO EXPERT OPINION ON ORPHAN DRUGS LA English DT Review DE BASKET trials; molecular subtypes; orphan drugs; umbrella trials ID MEDULLARY-THYROID CANCER; NEUROFIBROMATOSIS CLINICAL-TRIALS; GIANT-CELL ASTROCYTOMAS; PHASE-II TRIAL; PLEXIFORM NEUROFIBROMAS; YOUNG-ADULTS; TUBEROUS SCLEROSIS; PEDIATRIC-PATIENTS; INHIBITOR; CHILDREN AB Introduction: Rare tumors account for one fourth of adult tumors; in children, rare tumors represent approximately 15-20% of childhood malignancies, thus accounting for a significant burden of disease. The rarity of these individual diseases creates many challenges, from developing a thorough understanding of the disease pathophysiology, clinical characterization, to the conduct of meaningful clinical trials and eventually the development of effective therapies.Areas covered: Despite these challenges, substantial advances have been made in recent years including the development of novel clinical trial designs and endpoints including molecularly driven treatment trials that have resulted in approval of novel therapies for rare diseases. Collaboration amongst basic and clinical researchers, patient advocacy groups, industry and regulatory agencies has proven successful in select cases and holds promise for future progress in the treatment of rare tumors. In this review, we will highlight several examples of trials for rare tumors, with a focus on examples from pediatric oncology, where strong, nationwide collaborative groups have existed for many years.Expert opinion: Future progress in developing therapies for rare tumors will depend not only on continued scientific advances, but also on collaboration between investigators from various disciplines, institutions, regulatory agencies and patient advocacy groups. C1 [Bradford, Diana] Childrens Natl Med Ctr, Dept Hematol Oncol, Washington, DC 20010 USA. [Bradford, Diana; Reilly, Karlyne M.; Widemann, Brigitte C.; Sandler, Abby] NCI, NIH, Bethesda, MD 20892 USA. [Kummar, Shivaani] Stanford Univ, Sch Med, Palo Alto, CA 94304 USA. RP Kummar, S (reprint author), Stanford Univ, Sch Med, Palo Alto, CA 94304 USA. EM skummar@stanford.edu NR 60 TC 0 Z9 0 U1 3 U2 8 PU TAYLOR & FRANCIS LTD PI ABINGDON PA 2-4 PARK SQUARE, MILTON PARK, ABINGDON OR14 4RN, OXON, ENGLAND SN 2167-8707 J9 EXPERT OPIN ORPHAN D JI Exp. Opin. Orphan Drugs PD JAN 2 PY 2016 VL 4 IS 1 BP 93 EP 103 DI 10.1517/21678707.2016.1120663 PG 11 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA CZ9EM UT WOS:000367400600004 ER PT J AU Wang, H Shi, TJ Qian, WJ Liu, T Kagan, J Srivastava, S Smith, RD Rodland, KD Camp, DG AF Wang, Hui Shi, Tujin Qian, Wei-Jun Liu, Tao Kagan, Jacob Srivastava, Sudhir Smith, Richard D. Rodland, Karin D. Camp, David G. TI The clinical impact of recent advances in LC-MS for cancer biomarker discovery and verification SO EXPERT REVIEW OF PROTEOMICS LA English DT Review DE LC-MS; cancer biomarker; proteomics; targeted quantification; selected reaction monitoring; multiple reaction monitoring; isobaric labelling; label-free; PRISM ID TARGETED MASS-SPECTROMETRY; QUANTITATIVE PROTEOMIC ANALYSIS; REACTION MONITORING METHODS; LABEL-FREE QUANTIFICATION; BREAST-CANCER; LIQUID-CHROMATOGRAPHY; PROTEIN QUANTIFICATION; SHOTGUN PROTEOMICS; HIGH-RESOLUTION; ACCURATE MASS AB Mass spectrometry (MS) -based proteomics has become an indispensable tool with broad applications in systems biology and biomedical research. With recent advances in liquid chromatography (LC) and MS instrumentation, LC-MS is making increasingly significant contributions to clinical applications, especially in the area of cancer biomarker discovery and verification. To overcome challenges associated with analyses of clinical samples (for example, a wide dynamic range of protein concentrations in bodily fluids and the need to perform high throughput and accurate quantification of candidate biomarker proteins), significant efforts have been devoted to improve the overall performance of LC-MS-based clinical proteomics platforms. Reviewed here are the recent advances in LC-MS and its applications in cancer biomarker discovery and quantification, along with the potentials, limitations and future perspectives. C1 [Wang, Hui; Shi, Tujin; Qian, Wei-Jun; Liu, Tao; Smith, Richard D.; Rodland, Karin D.; Camp, David G.] Pacific NW Natl Lab, Div Biol Sci, Richland, WA 99352 USA. [Kagan, Jacob; Srivastava, Sudhir] NCI, Canc Prevent Div, Rockville, MD USA. RP Camp, DG (reprint author), Pacific NW Natl Lab, Div Biol Sci, Richland, WA 99352 USA. EM dave.camp@pnnl.gov RI Smith, Richard/J-3664-2012 OI Smith, Richard/0000-0002-2381-2349 FU National Institutes of Health [U24-CA-160019, P41GM103493, DP2OD006668, UC4 DK104167]; National Cancer Institute Early Detection Research Network [Y01-CN-05013-29] FX Parts of this work were supported by National Institutes of Health grants U24-CA-160019, P41GM103493, DP2OD006668, UC4 DK104167 and a National Cancer Institute Early Detection Research Network Interagency Agreement (No. Y01-CN-05013-29). The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed. NR 148 TC 2 Z9 2 U1 3 U2 34 PU TAYLOR & FRANCIS LTD PI ABINGDON PA 2-4 PARK SQUARE, MILTON PARK, ABINGDON OR14 4RN, OXON, ENGLAND SN 1478-9450 EI 1744-8387 J9 EXPERT REV PROTEOMIC JI Expert Rev. Proteomics PD JAN 2 PY 2016 VL 13 IS 1 BP 99 EP 114 DI 10.1586/14789450.2016.1122529 PG 16 WC Biochemical Research Methods SC Biochemistry & Molecular Biology GA CZ8LK UT WOS:000367351000002 PM 26581546 ER PT J AU Jones, TD Carter, PJ Pluckthun, A Vasquez, M Holgate, RGE Hotzel, I Popplewell, AG Parren, PWHI Enzelberger, M Rademaker, HJ Clark, MR Lowe, DC Dahiyat, BI Smith, V Lambert, JM Wu, H Reilly, M Haurum, JS Dubel, S Huston, JS Schirrmann, T Janssen, RAJ Steegmaier, M Gross, JA Bradbury, ARM Burton, DR Dimitrov, DS Chester, KA Glennie, MJ Davies, J Walker, A Martin, S McCafferty, J Baker, MP AF Jones, Tim D. Carter, Paul J. Plueckthun, Andreas Vasquez, Max Holgate, Robert G. E. Hoetzel, Isidro Popplewell, Andrew G. Parren, Paul W. H. I. Enzelberger, Markus Rademaker, Hendrik J. Clark, Michael R. Lowe, David C. Dahiyat, Bassil I. Smith, Victoria Lambert, John M. Wu, Herren Reilly, Mary Haurum, John S. Duebel, Stefan Huston, James S. Schirrmann, Thomas Janssen, Richard A. J. Steegmaier, Martin Gross, Jane A. Bradbury, Andrew R. M. Burton, Dennis R. Dimitrov, Dimiter S. Chester, Kerry A. Glennie, Martin J. Davies, Julian Walker, Adam Martin, Steve McCafferty, John Baker, Matthew P. TI The INNs and outs of antibody nonproprietary names SO MABS LA English DT Article DE antibody; chimeric; Complementarity Determining Region (CDR); definition; framework; humanized; International Nonproprietary Name (INN); International Immunogenetics Information System (IMGT); monoclonal; World Health Organization (WHO) ID MONOCLONAL-ANTIBODY; EFFICIENT GENERATION; B-CELLS; HUMANIZATION; IMMUNOGLOBULIN; MICE; FRAMEWORK; IMMUNIZATION; SEQUENCES; LIBRARIES AB An important step in drug development is the assignment of an International Nonproprietary Name (INN) by the World Health Organization (WHO) that provides healthcare professionals with a unique and universally available designated name to identify each pharmaceutical substance. Monoclonal antibody INNs comprise a -mab suffix preceded by a substem indicating the antibody type, e.g., chimeric (-xi-), humanized (-zu-), or human (-u-). The WHO publishes INN definitions that specify how new monoclonal antibody therapeutics are categorized and adapts the definitions to new technologies. However, rapid progress in antibody technologies has blurred the boundaries between existing antibody categories and created a burgeoning array of new antibody formats. Thus, revising the INN system for antibodies is akin to aiming for a rapidly moving target. The WHO recently revised INN definitions for antibodies now to be based on amino acid sequence identity. These new definitions, however, are critically flawed as they are ambiguous and go against decades of scientific literature. A key concern is the imposition of an arbitrary threshold for identity against human germline antibody variable region sequences. This leads to inconsistent classification of somatically mutated human antibodies, humanized antibodies as well as antibodies derived from semi-synthetic/synthetic libraries and transgenic animals. Such sequence-based classification implies clear functional distinction between categories (e.g., immunogenicity). However, there is no scientific evidence to support this. Dialog between the WHO INN Expert Group and key stakeholders is needed to develop a new INN system for antibodies and to avoid confusion and miscommunication between researchers and clinicians prescribing antibodies. C1 [Jones, Tim D.; Holgate, Robert G. E.; Baker, Matthew P.] Antitope Ltd, Cambridge CB22 3AT, England. [Carter, Paul J.; Hoetzel, Isidro] Genentech Inc, San Francisco, CA 94080 USA. [Plueckthun, Andreas] Univ Zurich, Dept Biochem, CH-8057 Zurich, Switzerland. [Vasquez, Max] Adimab LLC, Lebanon, NH 03766 USA. [Popplewell, Andrew G.] UCB Pharma, Slough SL1 3WE, Berks, England. [Parren, Paul W. H. I.; Rademaker, Hendrik J.] Genmab, NL-3508 AD Utrecht, Netherlands. [Parren, Paul W. H. I.] Leiden Univ, Med Ctr, Dept Immunohematol & Blood Transfus, NL-2333 ZA Leiden, Netherlands. [Enzelberger, Markus] MorphoSys AG, Martinsried, Germany. [Clark, Michael R.] Clark Antibodies Ltd, Cambridge CB1 1HW, England. [Lowe, David C.] MedImmune Ltd, Cambridge CB21 6GH, England. [Dahiyat, Bassil I.] Xencor, Monrovia, CA 91016 USA. [Smith, Victoria] Gilead Sci Inc, Foster City, CA 94404 USA. [Lambert, John M.] ImmunoGen Inc, Waltham, MA 02451 USA. [Wu, Herren] MedImmune, Gaithersburg, MD 20878 USA. [Reilly, Mary] Opsona Therapeut Ltd, Dublin 2, Ireland. [Haurum, John S.] F Star Biotechnol Ltd, Cambridge CB22 3AT, England. [Duebel, Stefan] Tech Univ Carolo Wilhelmina Braunschweig, Inst Biochem Biotechnol & Bioinformat, D-38106 Braunschweig, Germany. [Huston, James S.] Antibody Soc, Watertown, MA 02472 USA. [Huston, James S.] Huston Bioconsulting LLC, Watertown, MA 02472 USA. [Schirrmann, Thomas] Yumab GmbH, D-38106 Braunschweig, Germany. [Janssen, Richard A. J.] Galapagos NV, NL-2333 CL Leiden, Netherlands. [Steegmaier, Martin] Roche Innovat Ctr Penzberg, Large Mol Res, Roche Pharmaceut Res & Early Dev, D-82377 Penzberg, Germany. [Gross, Jane A.] Emergent BioSolut, Seattle, WA 98121 USA. [Bradbury, Andrew R. M.] Los Alamos Natl Lab, Biosci Div, Los Alamos, NM 87545 USA. [Burton, Dennis R.] Scripps Res Inst, La Jolla, CA 92037 USA. [Dimitrov, Dimiter S.] NCI, Prot Interact Sect, Canc & Inflammat Program, Ctr Canc Res, Frederick, MD 21702 USA. [Chester, Kerry A.] UCL, Inst Canc, London WC1E 6BT, England. [Glennie, Martin J.] Univ Southampton, Fac Med, Southampton Gen Hosp, Antibody & Vaccine Grp,Canc Sci Unit, Southampton SO16 6YD, Hants, England. [Davies, Julian] Lilly Biotechnol Ctr, San Diego, CA 92121 USA. [Walker, Adam] Addenbrookes Hosp, Addenbrookes Ctr Clin Invest, GSK, Cambridge CB2 2GG, England. [Martin, Steve] GSK, Med Res Ctr, Stevenage SG1 2NY, Herts, England. [McCafferty, John] Iontas Ltd, Cambridge CB22 3AT, England. RP Baker, MP (reprint author), Antitope Ltd, Babraham Res Campus, Cambridge CB22 3AT, England. EM matthew.baker@abzena.com RI Clark, Michael/D-2479-2011; OI Clark, Michael/0000-0002-5539-4997; Bradbury, Andrew/0000-0002-5567-8172; Dubel, Stefan/0000-0001-8811-7390; Pluckthun, Andreas/0000-0003-4191-5306; Parren, Paul/0000-0002-4365-3859 NR 46 TC 3 Z9 3 U1 1 U2 7 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 530 WALNUT STREET, STE 850, PHILADELPHIA, PA 19106 USA SN 1942-0862 EI 1942-0870 J9 MABS-AUSTIN JI mAbs PD JAN 2 PY 2016 VL 8 IS 1 BP 1 EP 9 DI 10.1080/19420862.2015.1114320 PG 9 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA CZ9CJ UT WOS:000367395100001 PM 26716992 ER PT J AU Zevin, JD Miller, B AF Zevin, Jason D. Miller, Brett TI Introduction to the special issue. Advancing the state-of-the-science in reading research through modeling SO SCIENTIFIC STUDIES OF READING LA English DT Editorial Material ID VISUAL WORD RECOGNITION; DUAL-ROUTE; DYSLEXIA; DISABILITY; AGREEMENT; INSIGHTS; CHINESE; ALOUD; RTI C1 [Zevin, Jason D.] Univ So Calif, Los Angeles, CA 90089 USA. [Miller, Brett] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, US Natl Inst Hlth, Bethesda, MD USA. RP Zevin, JD (reprint author), Univ So Calif, Dept Psychol, SGM 501,3620 South McClintock Ave, Los Angeles, CA 90089 USA. EM zevin@usc.edu FU Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) [P01 HD001994, P01 HD070837] FX Support for Jason Zevin is provided in part by P01 HD001994 and P01 HD070837 from the Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD). NR 21 TC 0 Z9 0 U1 5 U2 16 PU ROUTLEDGE JOURNALS, TAYLOR & FRANCIS LTD PI ABINGDON PA 2-4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXON, ENGLAND SN 1088-8438 EI 1532-799X J9 SCI STUD READ JI Sci. Stud. Read. PD JAN 2 PY 2016 VL 20 IS 1 SI SI BP 1 EP 5 DI 10.1080/10888438.2015.1118480 PG 5 WC Education & Educational Research; Psychology, Educational SC Education & Educational Research; Psychology GA DA1HM UT WOS:000367546900001 PM 26966346 ER PT J AU Odegard, JM Flynn, PA Campbell, DJ Robbins, SH Dong, LC Wang, KN ter Meulen, J Cohen, JI Koelle, DM AF Odegard, Jared M. Flynn, Patrick A. Campbell, David J. Robbins, Scott H. Dong, Lichun Wang, Kening ter Meulen, Jan Cohen, Jeffrey I. Koelle, David M. TI A novel HSV-2 subunit vaccine induces GLA-dependent CD4 and CD8 T cell responses and protective immunity in mice and guinea pigs SO VACCINE LA English DT Article DE HSV-2 vaccine; GLA adjuvant; CD8 T cells; CD4 T cells ID HERPES-SIMPLEX-VIRUS; TYPE-2 GENITAL-INFECTION; PLACEBO-CONTROLLED TRIAL; GLYCOPROTEIN-D; TEGUMENT PROTEINS; ANTIBODY-RESPONSES; DENDRITIC CELLS; TLR4 AGONIST; IFN-GAMMA; B-CELLS AB Background/objectives: There is currently no licensed prophylactic or therapeutic vaccine for HSV-2 infection. Methods: We developed a novel preclinical vaccine candidate, G103, consisting of three recombinantly expressed HSV-2 proteins (gD and the UL19 and UL25 gene products) adjuvanted with the potent synthetic TLR4 agonist glucopyranosyl lipid A (GLA) formulated in stable emulsion. The vaccine was tested for immunogenicity and efficacy in pre-clinical models for preventative and therapeutic vaccination. Results: Vaccination of mice with G103 elicited antigen-specific binding and neutralizing antibody responses, as well as robust CD4 and CD8 effector and memory T cells. The T cell responses were further boosted by subsequent challenge with live virus. Prophylactic immunization completely protected against lethal intravaginal HSV-2 infection in mice, with only transient replication of virus in the genital mucosa and sterilizing immunity in dorsal root ganglia. Supporting the use of G103 therapeutically, the vaccine expanded both CD4 and CD8 T cells induced in mice by previous infection with HSV-2. In the guinea pig model of recurrent HSV-2 infection, therapeutic immunization with G103 was approximately 50% effective in reducing the number of lesions per animal as well as the overall lesions score. Conclusions: Taken together, the data show that G103 is a viable candidate for development of a novel prophylactic and therapeutic HSV-2 vaccine. (C) 2015 Elsevier Ltd. All rights reserved. C1 [Odegard, Jared M.; Flynn, Patrick A.; Campbell, David J.; Robbins, Scott H.; ter Meulen, Jan] Immune Design, Seattle, WA 98102 USA. [Dong, Lichun; Koelle, David M.] Univ Washington, Dept Med, Seattle, WA 98195 USA. [Wang, Kening; Cohen, Jeffrey I.] NIAID, Med Virol Sect, Infect Dis Lab, NIH, Bethesda, MD 20892 USA. [Koelle, David M.] Benaroya Res Inst, Seattle, WA 98101 USA. [Koelle, David M.] Univ Washington, Dept Lab Med, Seattle, WA 98195 USA. [Koelle, David M.] Univ Washington, Dept Global Hlth, Seattle, WA 98195 USA. [Koelle, David M.] Fred Hutchinson Canc Res Ctr, Vaccine & Infect Dis Div, Seattle, WA 98109 USA. RP ter Meulen, J (reprint author), Immune Design, Seattle, WA 98102 USA. EM jan.termeulen@immunedesign.com RI Koelle, David/Q-6529-2016 OI Koelle, David/0000-0003-1255-9023 FU National Institute of Allergy and Infectious Diseases; NIAID; Immune Design FX The authors thank Dr. David Knipe, Harvard Medical School, for providing virus strain HSV-2 186, and Dr. Larry Corey and Dr. Carlos Paya for critical reading of the manuscript. K.W. and J.I.C. are supported by the intramural research program of the National Institute of Allergy and Infectious Diseases. This work was supported by a Cooperative Research and Development Agreement between NIAID and Immune Design. We thank Daniel Y. Li for assistance with the guinea pig experiments and Andrea Parsons for performing assays. NR 64 TC 7 Z9 7 U1 0 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 JAN 2 PY 2016 VL 34 IS 1 BP 101 EP 109 DI 10.1016/j.vaccine.2015.10.137 PG 9 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA DA0LV UT WOS:000367489500015 PM 26571309 ER PT J AU Lai, C Karp, JE Hourigan, CS AF Lai, Catherine Karp, Judith E. Hourigan, Christopher S. TI Precision medicine for acute myeloid leukemia SO EXPERT REVIEW OF HEMATOLOGY LA English DT Editorial Material DE AML; leukemia; measurable residual disease; minimal residual disease; MRD; personalized medicine; precision medicine; screening; sensitivity ID MINIMAL RESIDUAL DISEASE; THERAPY; PROGRESS; FUTURE AB The goal of precision medicine is to personalize therapy based on individual patient variation, to correctly select the right treatment, for the right patient, at the right time. Acute myeloid leukemia (AML) is a heterogeneous collection of myeloid malignancies with diverse genetic etiology and the potential for intra-patient clonal evolution over time. We discuss here how the precision medicine paradigm might be applied to the care of AML patients by focusing on the potential roles of targeting therapy by patient-specific somatic mutations and aberrant pathways, ex-vivo drug sensitivity and resistance testing, high sensitivity measurements of residual disease burden and biology along with potential clinical trial and regulatory constraints. C1 [Lai, Catherine; Karp, Judith E.; Hourigan, Christopher S.] NHLBI, Myeloid Malignancies Sect, Hematol Branch, NIH, Bethesda, MD 20892 USA. [Karp, Judith E.] Johns Hopkins Sch Med, Sidney Kimmel Comprehens Canc Ctr, Div Hematol Malignancies, Baltimore, MD USA. RP Hourigan, CS (reprint author), NHLBI, Myeloid Malignancies Sect, Hematol Branch, NIH, Bldg 10, Bethesda, MD 20892 USA. EM hourigan@nih.gov RI Hourigan, Christopher/S-2476-2016 OI Hourigan, Christopher/0000-0002-6189-8067 FU Intramural NIH HHS [ZIA HL006163-03] NR 22 TC 2 Z9 2 U1 3 U2 10 PU TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXON, ENGLAND SN 1747-4086 EI 1747-4094 J9 EXPERT REV HEMATOL JI Expert Rev. Hematol. PD JAN 2 PY 2016 VL 9 IS 1 BP 1 EP 3 DI 10.1586/17474086.2016.1107471 PG 3 WC Hematology SC Hematology GA CZ8ZF UT WOS:000367386900001 PM 26514194 ER PT J AU Correa-de-Araujo, R AF Correa-de-Araujo, Rosaly TI Evidence-Based Practice in the United States: Challenges, Progress, and Future Directions SO HEALTH CARE FOR WOMEN INTERNATIONAL LA English DT Article ID DECISION-MAKING; CLINICAL-TRIAL; WOMENS HEALTH; CARE; POSTPARTUM; TRANSITION; AMERICANS; SYMPTOMS; PATTERNS; MEDICINE AB Scientific literature demonstrates that advances in evidence-based nursing have improved systems of care and women's health outcomes. Experts agree that nurses worldwide can play a key role in building such evidence and working with interdisciplinary health care teams and systems to accelerate its implementation. C1 [Correa-de-Araujo, Rosaly] NIA, Div Geriatr & Clin Gerontol, NIH, US Dept Hlth & Human Serv, Bethesda, MD 20892 USA. RP Correa-de-Araujo, R (reprint author), NIA, Div Geriatr & Clin Gerontol, NIH, US Dept Hlth & Human Serv, 7201 Wisconsin Ave,Suite 3C307, Bethesda, MD 20892 USA. EM rosaly.correa-de-araujo@nih.gov FU Intramural NIH HHS [Z99 AG999999] NR 52 TC 0 Z9 0 U1 1 U2 12 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 530 WALNUT STREET, STE 850, PHILADELPHIA, PA 19106 USA SN 0739-9332 EI 1096-4665 J9 HEALTH CARE WOMEN IN JI Health Care Women Int. PD JAN 2 PY 2016 VL 37 IS 1 BP 2 EP 22 DI 10.1080/07399332.2015.1102269 PG 21 WC Public, Environmental & Occupational Health; Women's Studies SC Public, Environmental & Occupational Health; Women's Studies GA CZ3KY UT WOS:000367004200002 PM 26473771 ER PT J AU Goodyear, K Lee, MR O'Hara, M Chernyak, S Walter, H Parasuraman, R Krueger, F AF Goodyear, Kimberly Lee, Mary R. O'Hara, Martin Chernyak, Sergey Walter, Henrik Parasuraman, Raja Krueger, Frank TI Oxytocin influences intuitions about the relationship between belief in free will and moral responsibility SO SOCIAL NEUROSCIENCE LA English DT Article DE Oxytocin; Free will; Moral responsibility; Determinism; Affiliation ID HUMAN BRAIN; EXPERIMENTAL PHILOSOPHY; INTRANASAL OXYTOCIN; SOCIAL COGNITION; NEURAL CIRCUITRY; FOLK INTUITIONS; HUMANS; RESPONSES; JUDGMENT; BEHAVIOR AB Philosophers have proposed that laypeople can have deterministic or indeterministic intuitions about the relationship between free will and moral responsibility. However, the psychophysiological mechanisms that generate these extreme intuitions are still underexplored. Exogenous oxytocin offers a unique opportunity to gain a deeper understanding of these underlying mechanisms, since this neuropeptide influences a wide range of outcomes related to social cognition and prosociality. This study investigated the effects of intranasal oxytocin on intuitions about the relationship between free will and moral responsibility by applying a randomized, double-blind, placebo-controlled, between-subject design. Healthy male participants rated the moral responsibility of a hypothetical offender, who committed crimes in either a primed deterministic or an indeterministic universe. Under placebo, participants held the offender more morally responsible when acting in an indeterministic compared to a deterministic universe, which could be accredited to recognition of the offender's freely chosen action to commit the crimes. Under oxytocin, participants rated the offender's actions with greater leniency and similarly assigned lower moral responsibility in both universes. These findings strengthen the assumption that a person can have different intuitions about the relationship between free will and moral responsibility, which can be presumably dependent on motivational states associated with affiliation. C1 [Goodyear, Kimberly; Chernyak, Sergey; Krueger, Frank] George Mason Univ, Dept Mol Neurosci, Fairfax, VA 22030 USA. [Lee, Mary R.] NIAAA, Lab Clin & Translat Studies, Bethesda, MD USA. [O'Hara, Martin] Fairfax Hosp, Virginia Hosp Ctr, Arlington, VA USA. [Walter, Henrik] Charite, Div Mind & Brain Res, Dept Psychiat & Psychotherapy, D-13353 Berlin, Germany. [Parasuraman, Raja; Krueger, Frank] George Mason Univ, Dept Psychol, Fairfax, VA 22030 USA. RP Krueger, F (reprint author), George Mason Univ, Dept Psychol, Mol Neurosci Dept, 4400 Univ Dr,MSN 2A1, Fairfax, VA 22030 USA. EM fkrueger@gmu.edu RI Walter, Henrik/O-2612-2013 NR 60 TC 1 Z9 1 U1 4 U2 12 PU ROUTLEDGE JOURNALS, TAYLOR & FRANCIS LTD PI ABINGDON PA 2-4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXON, ENGLAND SN 1747-0919 EI 1747-0927 J9 SOC NEUROSCI-UK JI Soc. Neurosci. PD JAN 2 PY 2016 VL 11 IS 1 BP 88 EP 96 DI 10.1080/17470919.2015.1037463 PG 9 WC Neurosciences; Psychology SC Neurosciences & Neurology; Psychology GA CZ8FS UT WOS:000367336200007 PM 25916658 ER PT J AU Reed, SG Coler, RN Mondal, D Kamhawi, S Valenzuela, JG AF Reed, S. G. Coler, R. N. Mondal, D. Kamhawi, S. Valenzuela, J. G. TI Leishmania vaccine development: exploiting the host-vector-parasite interface SO EXPERT REVIEW OF VACCINES LA English DT Review DE Leishmania; vaccine; sand fly; saliva; adjuvant ID DELAYED-TYPE HYPERSENSITIVITY; ACTIVE VISCERAL LEISHMANIASIS; LUTZOMYIA-LONGIPALPIS SALIVA; CELL-MEDIATED-IMMUNITY; GROWTH-FACTOR-BETA; SAND FLY SALIVA; CUTANEOUS LEISHMANIASIS; DONOVANI INFECTION; RECOMBINANT K-39; CLONED ANTIGEN AB Visceral leishmaniasis (VL) is a disease transmitted by phlebotomine sand flies, fatal if untreated, and with no available human vaccine. In rodents, cellular immunity to Leishmania parasite proteins as well as salivary proteins of the sand fly is associated with protection, making them worthy targets for further exploration as vaccines. This review discusses the notion that a combination vaccine including Leishmania and vector salivary antigens may improve vaccine efficacy by targeting the parasite at its most vulnerable stage just after transmission. Furthermore, we put forward the notion that better modeling of natural transmission is needed to test efficacy of vaccines. For example, the fact that individuals living in endemic areas are exposed to sand fly bites and will mount an immune response to salivary proteins should be considered in pre-clinical and clinical evaluation of leishmaniasis vaccines. Nevertheless, despite remaining obstacles there is good reason to be optimistic that safe and effective vaccines against leishmaniasis can be developed. C1 [Reed, S. G.; Coler, R. N.] Infect Dis Res Inst, Seattle, WA 98102 USA. [Reed, S. G.; Coler, R. N.] Univ Washington, Dept Global Hlth, Seattle, WA 98195 USA. [Mondal, D.] Int Ctr Diarrhoeal Dis Res, Ctr Nutr & Food Secur, Parasitol Lab, Dhaka 1000, Bangladesh. [Kamhawi, S.; Valenzuela, J. G.] NIAID, Vector Mol Biol Sect, LMVR, NIH, Rockville, MD USA. RP Reed, SG (reprint author), Infect Dis Res Inst, Seattle, WA 98102 USA. EM Steven.Reed@idri.org; jvalenzuela@niaid.nih.gov FU National Institute of Allergy and Infectious Diseases, NIH; Bill & Melinda Gates Foundation [631, 39129, 49932]; NIAID of the National Institutes of Health [R01AI025038] FX Support for this work was provided by the Intramural Research Program at the National Institute of Allergy and Infectious Diseases, NIH (JG Valenzuela and S Kamhawi). This research was supported in part with funding from the Bill & Melinda Gates Foundation, under grants 631, 39129 and 49932 and by Grant # R01AI025038 from NIAID of the National Institutes of Health. The content is solely the responsibility of the authors and does not necessarily represent the official views of the Bill & Melinda Gates Foundation or the National Institutes of Health. SG Reed is a co-inventor on a patent of leishmaniasis vaccine development. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed. NR 78 TC 5 Z9 5 U1 1 U2 14 PU TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXON, ENGLAND SN 1476-0584 EI 1744-8395 J9 EXPERT REV VACCINES JI Expert Rev. Vaccines PD JAN 2 PY 2016 VL 15 IS 1 BP 81 EP 90 DI 10.1586/14760584.2016.1105135 PG 10 WC Immunology SC Immunology GA CY1WO UT WOS:000366199100003 PM 26595093 ER PT J AU Cho, N Kim, HW Lee, HK Jeon, BJ Sung, SH AF Cho, Namki Kim, Hyeon Woo Lee, Hee Kyoung Jeon, Byung Ju Sung, Sang Hyun TI Ameliorative effect of betulin from Betula platyphylla bark on scopolamine-induced amnesic mice SO BIOSCIENCE BIOTECHNOLOGY AND BIOCHEMISTRY LA English DT Article DE betulin; passive avoidance; Y-maze; Morris water maze; cognitive enhancement ID ALZHEIMERS-DISEASE; SCROPHULARIA-BUERGERIANA; ANTIOXIDANT ACTIVITIES; STANDARDIZED EXTRACT; MEMORY IMPAIRMENT; VAR. JAPONICA; LONG-TERM; IN-VITRO; ACID; GLUTATHIONE AB Alzheimer's disease (AD) is a neurodegenerative disease induced by cholinergic neuron damage or amyloid-beta aggregation in the basal forebrain region and resulting in cognitive disorder. We previously reported on the neuroprotective effects of Betula platyphylla bark (BPB) in an amyloid-beta-induced amnesic mouse model. In this study, we obtained a cognitive-enhancing compound by assessing results using a scopolamine-induced amnesic mouse model. Our results show that oral treatment of mice with BPB and betulin significantly ameliorated scopolamine-induced memory deficits in both passive avoidance and Y-maze tests. In the Morris water maze test, administration of BPB and betulin significantly improved memory and cognitive function indicating the formation of working and reference memories in treated mice. Moreover, betulin significantly increased glutathione content in mouse hippocampus, and the increase was greater than that from betulinic acid treatment. We conclude that BPB and its active component betulin have potential as therapeutic, cognitive enhancer in AD. C1 [Cho, Namki] NCI, Mol Targets Lab, Frederick, MD 21701 USA. [Cho, Namki; Kim, Hyeon Woo; Sung, Sang Hyun] Seoul Natl Univ, Coll Pharm, Seoul, South Korea. [Cho, Namki; Kim, Hyeon Woo; Sung, Sang Hyun] Seoul Natl Univ, Pharmaceut Sci Res Inst, Seoul, South Korea. [Lee, Hee Kyoung; Jeon, Byung Ju] Elcom Sci Co Ltd, Inst Life Sci, Seoul, South Korea. RP Sung, SH (reprint author), Seoul Natl Univ, Coll Pharm, Seoul, South Korea. EM shsung@snu.ac.kr FU Forest Science and Technology Project [S121214L120100]; Korea Forest Service FX This work was supported by the Forest Science and Technology Project [S121214L120100] with funding provided by the Korea Forest Service. NR 26 TC 0 Z9 0 U1 1 U2 8 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 JAN 2 PY 2016 VL 80 IS 1 BP 166 EP 171 DI 10.1080/09168451.2015.1072460 PG 6 WC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Chemistry, Applied; Food Science & Technology SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Chemistry; Food Science & Technology GA CX3VL UT WOS:000365627500022 ER PT J AU Meehan, CA Cochran, E Kassai, A Brown, RJ Gorden, P AF Meehan, Cristina Adelia Cochran, Elaine Kassai, Andrea Brown, Rebecca J. Gorden, Phillip TI Metreleptin for injection to treat the complications of leptin deficiency in patients with congenital or acquired generalized lipodystrophy SO EXPERT REVIEW OF CLINICAL PHARMACOLOGY LA English DT Review DE lipodystrophy; leptin; metreleptin; metabolic syndrome; insulin resistance ID REVERSES INSULIN-RESISTANCE; BASE-LINE CHARACTERISTICS; REPLACEMENT THERAPY; RECOMBINANT LEPTIN; NONALCOHOLIC STEATOHEPATITIS; OBESITY; MUTATIONS; EFFICACY; LIVER; HETEROGENEITY AB The lipodystrophies represent a class of diseases characterized by leptin deficiency. Leptin deficiency is associated with a severe form of the metabolic syndrome characterized by dyslipidemia, insulin resistance, diabetes, and ovarian dysfunction. Metreleptin is the pharmaceutical derived product that has been approved by the Food and Drug Administration (FDA) to treat the severe metabolic abnormalities of the generalized forms of lipodystrophy. Herein we describe the properties of metreleptin, its use in patients, which includes the administration of the drug and how it may be acquired by medical professionals as well as its safety, tolerability, and properties. Finally, we speculate on future uses and development of metreleptin. C1 [Meehan, Cristina Adelia; Cochran, Elaine; Kassai, Andrea; Brown, Rebecca J.; Gorden, Phillip] NIDDK, Diabet Endocrinol & Obes Branch, NIH, Bethesda, MD 20892 USA. RP Meehan, CA (reprint author), NIDDK, Diabet Endocrinol & Obes Branch, NIH, Bethesda, MD 20892 USA. EM PhillipG@intra.niddk.nih.gov FU NIH FX The authors were supported by NIH intermural support. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed. NR 51 TC 4 Z9 5 U1 2 U2 4 PU TAYLOR & FRANCIS LTD PI ABINGDON PA 2-4 PARK SQUARE, MILTON PARK, ABINGDON OR14 4RN, OXON, ENGLAND SN 1751-2433 EI 1751-2441 J9 EXPERT REV CLIN PHAR JI Expert Rev. Clin. Pharmacol. PD JAN 2 PY 2016 VL 9 IS 1 BP 59 EP 68 DI 10.1586/17512433.2016.1096772 PG 10 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA CW9WJ UT WOS:000365348600001 PM 26465174 ER PT J AU Satoh, D Furuta, T Takahashi, F Endo, A Lee, C Bolch, WE AF Satoh, Daiki Furuta, Takuya Takahashi, Fumiaki Endo, Akira Lee, Choonsik Bolch, Wesley Emmett TI Age-dependent dose conversion coefficients for external exposure to radioactive cesium in soil SO JOURNAL OF NUCLEAR SCIENCE AND TECHNOLOGY LA English DT Article DE cesium; Monte Carlo calculation; radiation dose; conversion coefficient; external exposure; Fukushima nuclear accident ID PHANTOMS; SYSTEM; RADIONUCLIDES AB To estimate effective doses for members of the public exposed to external radiation from radioactive cesium (Cs-134 and Cs-137) deposited on the ground by the Fukushima nuclear accident, we calculate the conversion coefficients for converting activity concentration to effective dose rate by using the Particle and Heavy Ion Transport Code System. The data were produced from different age groups within the public (newborns; 1-, 5-, 10-, and 15-year-old children; and adults) for the situations in which radioactive cesium is distributed uniformly in the soil over a planar area and at specific depths of 0.0, 0.5, 2.5, 5.0, 10.0, and 50.0 g/cm(2). On the basis of the results, we also derive the conversion coefficients for exponentially distributed volumetric sources. In addition, we obtain the conversion coefficients that give the effective dose accumulated over the first and second months, the first year, and over a lifetime (50 years) because of the contamination remaining on the ground. These calculations indicate that the conversion coefficients to obtain the effective dose rate are higher for the younger ages compared with adults, but do not exceed the ambient dose equivalent rate. Furthermore, we find that the difference between the calculated effective dose rates according to the International Commission on Radiological Protection 1990 and 2007 Recommendations is small (7% maximum) for a ground contamination of radioactive cesium. C1 [Satoh, Daiki; Furuta, Takuya; Takahashi, Fumiaki; Endo, Akira] Japan Atom Energy Agcy, Nucl Sci & Engn Ctr, Tokai, Ibaraki 3191195, Japan. [Lee, Choonsik] NCI, Div Canc Epidemiol & Genet, NIH, Rockville, MD 20850 USA. [Bolch, Wesley Emmett] Univ Florida, Dept Biomed Engn, Gainesville, FL 32611 USA. RP Satoh, D (reprint author), Japan Atom Energy Agcy, Nucl Sci & Engn Ctr, Tokai, Ibaraki 3191195, Japan. EM satoh.daiki@jaea.go.jp NR 27 TC 2 Z9 3 U1 1 U2 15 PU TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXON, ENGLAND SN 0022-3131 EI 1881-1248 J9 J NUCL SCI TECHNOL JI J. Nucl. Sci. Technol. PD JAN 2 PY 2016 VL 53 IS 1 BP 69 EP 81 DI 10.1080/00223131.2015.1021286 PG 13 WC Nuclear Science & Technology SC Nuclear Science & Technology GA CW8HV UT WOS:000365241000006 ER PT J AU Resnik, DB Elliott, KC AF Resnik, David B. Elliott, Kevin C. TI The Ethical Challenges of Socially Responsible Science SO ACCOUNTABILITY IN RESEARCH-POLICIES AND QUALITY ASSURANCE LA English DT Article DE Ethics; objectivity; politics; scientific research; social responsibility; values ID POLICY AB Social responsibility is an essential part of the responsible conduct of research that presents difficult ethical questions for scientists. Recognizing one's social responsibilities as a scientist is an important first step toward exercising social responsibility, but it is only the beginning, since scientists may confront difficult value questions when deciding how to act responsibly. Ethical dilemmas related to socially responsible science fall into at least three basic categories: 1) dilemmas related to problem selection, 2) dilemmas related to publication and data sharing, and 3) dilemmas related to engaging society. In responding to these dilemmas, scientists must decide how to balance their social responsibilities against other professional commitments and how to avoid compromising their objectivity. In this article, we will examine the philosophical and ethical basis of social responsibility in science, discuss some of the ethical dilemmas related to exercising social responsibility, and make five recommendations to help scientists deal with these issues. C1 [Resnik, David B.] NIEHS, NIH, Res Triangle Pk, NC 27709 USA. [Elliott, Kevin C.] Michigan State Univ, Dept Fisheries & Wildlife, Lyman Briggs Coll, E Lansing, MI 48824 USA. [Elliott, Kevin C.] Michigan State Univ, Dept Philosophy, E Lansing, MI 48824 USA. RP Resnik, DB (reprint author), NIEHS, NIH, Box 12233,CU 03, Res Triangle Pk, NC 27709 USA. EM resnikd@niehs.nih.gov FU Intramural NIH HHS [ZIA ES102646-06, Z99 ES999999] NR 56 TC 0 Z9 0 U1 5 U2 48 PU TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXON, ENGLAND SN 0898-9621 EI 1545-5815 J9 ACCOUNT RES JI Account. Res. PD JAN 2 PY 2016 VL 23 IS 1 BP 31 EP 46 DI 10.1080/08989621.2014.1002608 PG 16 WC Medical Ethics SC Medical Ethics GA CV4EB UT WOS:000364217700004 PM 26193168 ER PT J AU Abramowitz, LK Hanover, JA AF Abramowitz, L. K. Hanover, J. A. TI Balancing Cell Growth and Apoptosis by Protein O-GlcNAcylation. SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract CT Annual Meeting of the American-Society-for-Cell-Biology (ASCB) CY DEC 03-07, 2016 CL San Francisco, CA SP Amer Soc Cell Biol C1 [Abramowitz, L. K.; Hanover, J. A.] NIDDK, NIH, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 EI 1939-4586 J9 MOL BIOL CELL JI Mol. Biol. Cell PY 2016 VL 27 MA P1369 PG 2 WC Cell Biology SC Cell Biology GA EN5LN UT WOS:000396047100370 ER PT J AU Aksenova, V Arnaoutov, A Smith, A Dasso, M AF Aksenova, V. Arnaoutov, A. Smith, A. Dasso, M. TI A new strategy for studying nuclear pore proteins in mitosis. SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract CT Annual Meeting of the American-Society-for-Cell-Biology (ASCB) CY DEC 03-07, 2016 CL San Francisco, CA SP Amer Soc Cell Biol C1 [Aksenova, V.; Arnaoutov, A.; Smith, A.; Dasso, M.] NICHHD, Sect Cell Cycle Regulat, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 EI 1939-4586 J9 MOL BIOL CELL JI Mol. Biol. 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TI Cellular effects of distinct missense mutations at spastin residue 499 that result in clinically different neurologic syndromes SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract CT Annual Meeting of the American-Society-for-Cell-Biology (ASCB) CY DEC 03-07, 2016 CL San Francisco, CA SP Amer Soc Cell Biol C1 [Boucekkine, H.; Renvoise, B.; Maldonado-Baez, L.; Cole, N. B.; Blackstone, C. D.] NINDS, Neurogenet Branch, NIH, Bethesdda, MD USA. [Boucekkine, H.] NIH, Med Res Scholars Program, Bldg 10, Bethesda, MD 20892 USA. [Boucekkine, H.] Univ Miami, Miller Sch Med, Miami, FL 33136 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 EI 1939-4586 J9 MOL BIOL CELL JI Mol. Biol. Cell PY 2016 VL 27 MA P1268 PG 1 WC Cell Biology SC Cell Biology GA EN5LN UT WOS:000396047100270 ER PT J AU Cannon, K Bridges, A Garten, M Zimmerberg, J Gladfelter, AS AF Cannon, K. Bridges, A. Garten, M. 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TI Noninvasive acoustic force spectroscopy for measuring apical surface membrane tension and intercellular adhesive forces in polarized epithelium SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract CT Annual Meeting of the American-Society-for-Cell-Biology (ASCB) CY DEC 03-07, 2016 CL San Francisco, CA SP Amer Soc Cell Biol C1 [Cartagena-Rivera, A. X.; Chadwick, R. S.] Natl Inst Deafness & Other Commun Disorders, NIH, Bethesda, MD USA. [Van Itallie, C. M.; Anderson, J. M.] NHLBI, NIH, Bldg 10, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 EI 1939-4586 J9 MOL BIOL CELL JI Mol. Biol. Cell PY 2016 VL 27 MA P1458 PG 2 WC Cell Biology SC Cell Biology GA EN5LN UT WOS:000396047100459 ER PT J AU Chandris, P Gupta, S Giannouli, C Dunn, T Shroff, H Proia, R AF Chandris, P. Gupta, S. Giannouli, C. Dunn, T. Shroff, H. Proia, R. TI Dynamics and nanoscale organization of key players in the de novo sphingolipid synthesis pathway unveiled by genetically encoded fluorescent reporters and super-resolution microscopy. SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract CT Annual Meeting of the American-Society-for-Cell-Biology (ASCB) CY DEC 03-07, 2016 CL San Francisco, CA SP Amer Soc Cell Biol C1 [Chandris, P.; Shroff, H.] NIBIB, Sect High Resolut Opt Imaging, NIH, Bethesda, MD USA. [Chandris, P.; Giannouli, C.; Proia, R.] NIDDK, Genet Dev & Dis Branch, NIH, Bethesda, MD 20892 USA. [Gupta, S.; Dunn, T.] Uniformed Serv Univ Hlth Sci, Dept Pharmacol, 4301 Jones Bridge Rd, Bethesda, MD 20814 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 EI 1939-4586 J9 MOL BIOL CELL JI Mol. Biol. 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Cell PY 2016 VL 27 MA P1578 PG 1 WC Cell Biology SC Cell Biology GA EN5LN UT WOS:000396047100580 ER PT J AU Galletta, BJ Fagerstrom, CJ Schoborg, TA McLamarrah, TA Ryniawec, JM Buster, DW Slep, KC Rogers, GC Rusan, NM AF Galletta, B. J. Fagerstrom, C. J. Schoborg, T. A. McLamarrah, T. A. Ryniawec, J. M. Buster, D. W. Slep, K. C. Rogers, G. C. Rusan, N. M. TI A Detailed Centrosome Interactome Reveals A Novel Role Of Plk4 And Provides Insight Into The Mechanisms Of Human Centrosome Disease SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract CT Annual Meeting of the American-Society-for-Cell-Biology (ASCB) CY DEC 03-07, 2016 CL San Francisco, CA SP Amer Soc Cell Biol C1 [Galletta, B. J.; Fagerstrom, C. J.; Schoborg, T. A.; Rusan, N. M.] NHLBI, Cell Biol & Physiol Ctr, Bldg 10, Bethesda, MD 20892 USA. [McLamarrah, T. A.; Ryniawec, J. M.; Buster, D. W.; Rogers, G. C.] Univ Arizona, Cellular & Mol Med, Tucson, AZ USA. [Slep, K. C.] Univ N Carolina, Biol, Chapel Hill, NC USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 EI 1939-4586 J9 MOL BIOL CELL JI Mol. Biol. Cell PY 2016 VL 27 MA P1070 PG 2 WC Cell Biology SC Cell Biology GA EN5LN UT WOS:000396047100076 ER PT J AU Ganti, K Massimi, P Manzo-Merino, J Tomaic, V Pim, DC Playford, M Lizano, M Roberts, S Kranjec, C Doorbar, J Banks, L AF Ganti, K. Massimi, P. Manzo-Merino, J. Tomaic, V. Pim, D. C. Playford, M. Lizano, M. Roberts, S. Kranjec, C. Doorbar, J. Banks, L. TI Interaction of the Human Papillomavirus E6 Oncoprotein with Sorting Nexin 27 modulates Endocytic Cargo Transport Pathways SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract CT Annual Meeting of the American-Society-for-Cell-Biology (ASCB) CY DEC 03-07, 2016 CL San Francisco, CA SP Amer Soc Cell Biol C1 [Ganti, K.] NIAID, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA. [Massimi, P.; Tomaic, V.; Pim, D. 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TI Assessment of VPS18 as candidate gene in an individual with undiagnosed disease and abnormal glycosylation. SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract CT Annual Meeting of the American-Society-for-Cell-Biology (ASCB) CY DEC 03-07, 2016 CL San Francisco, CA SP Amer Soc Cell Biol C1 [Hackbarth, M. E.; Kane, M. S.; Davids, M.; Wolfe, L.; Adams, D. R.; Gahl, W. A.; Malicdan, M. V.] NHGRI, Off Clin Director, NIH, Bethesda, MD 20892 USA. [Hackbarth, M. E.; Kane, M. S.; Davids, M.; Wolfe, L.; Adams, D. R.; Gahl, W. A.; Malicdan, M. V.] NHGRI, Undiagnosed Dis Program, NIH, Bethesda, MD 20892 USA. [Kane, M. S.] Inova Fairfax Hosp, Falls Church, VA USA. [He, M.] Childrens Hosp Philadelphia, Michael J Palmiere Metab Lab, Philadelphia, PA 19104 USA. [He, M.] Univ Penn, Dept Pathol & Lab Med, Philadelphia, PA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 EI 1939-4586 J9 MOL BIOL CELL JI Mol. Biol. Cell PY 2016 VL 27 MA P1281 PG 1 WC Cell Biology SC Cell Biology GA EN5LN UT WOS:000396047100283 ER PT J AU Hu, L Vecchiarelli, AG Mizuuchi, K Neuman, KC Liu, J AF Hu, L. Vecchiarelli, A. G. Mizuuchi, K. Neuman, K. C. Liu, J. TI Brownian ratchet mechanism of plasmid segregation SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract CT Annual Meeting of the American-Society-for-Cell-Biology (ASCB) CY DEC 03-07, 2016 CL San Francisco, CA SP Amer Soc Cell Biol C1 [Hu, L.; Neuman, K. C.; Liu, J.] NHLBI, NIH, Bldg 10, Bethesda, MD 20892 USA. [Vecchiarelli, A. G.; Mizuuchi, K.] NIDDK, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 EI 1939-4586 J9 MOL BIOL CELL JI Mol. Biol. Cell PY 2016 VL 27 MA P1539 PG 1 WC Cell Biology SC Cell Biology GA EN5LN UT WOS:000396047100541 ER PT J AU Jevtic, P Schibler, AC Pegoraro, G Misteli, T Levy, DL AF Jevtic, P. Schibler, A. C. Pegoraro, G. Misteli, T. Levy, D. L. TI Systematic identification of nuclear sizing factors by high-throughput imaging-based siRNA screening. SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract CT Annual Meeting of the American-Society-for-Cell-Biology (ASCB) CY DEC 03-07, 2016 CL San Francisco, CA SP Amer Soc Cell Biol C1 [Jevtic, P.; Levy, D. L.] Univ Wyoming, Mol Biol, Laramie, WY 82071 USA. [Schibler, A. C.; Misteli, T.] NCI, NIH, Bethesda, MD 20892 USA. [Pegoraro, G.] NCI, High Throughput Imaging Facil HiTIF, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 EI 1939-4586 J9 MOL BIOL CELL JI Mol. Biol. Cell PY 2016 VL 27 MA P1217 PG 2 WC Cell Biology SC Cell Biology GA EN5LN UT WOS:000396047100220 ER PT J AU Katkere, B Markley, RL Williamson, DR Shay, AE Prabhu, KS Kirimanjeswara, GS Carlson, BA AF Katkere, B. Markley, R. L. Williamson, D. R. Shay, A. E. Prabhu, K. S. Kirimanjeswara, G. S. Carlson, B. A. TI Selenoproteins regulate B cell functions by targeting B cell receptor-mediated antigen presentation pathway. SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract CT Annual Meeting of the American-Society-for-Cell-Biology (ASCB) CY DEC 03-07, 2016 CL San Francisco, CA SP Amer Soc Cell Biol C1 [Katkere, B.; Markley, R. L.; Williamson, D. R.; Shay, A. E.; Prabhu, K. S.; Kirimanjeswara, G. S.] Penn State Univ, Vet & Biomed Sci, University Pk, PA 16802 USA. [Carlson, B. A.] NCI, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 EI 1939-4586 J9 MOL BIOL CELL JI Mol. Biol. Cell PY 2016 VL 27 MA P1640 PG 2 WC Cell Biology SC Cell Biology GA EN5LN UT WOS:000396047100642 ER PT J AU Liu, L AF Liu, L. TI An inducible ER-Golgi tether facilitates ceramide transport to alleviate lipotoxicity. SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract CT Annual Meeting of the American-Society-for-Cell-Biology (ASCB) CY DEC 03-07, 2016 CL San Francisco, CA SP Amer Soc Cell Biol C1 [Liu, L.] NIDDH, NIH, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 EI 1939-4586 J9 MOL BIOL CELL JI Mol. Biol. Cell PY 2016 VL 27 MA P1329 PG 1 WC Cell Biology SC Cell Biology GA EN5LN UT WOS:000396047100331 ER PT J AU Mehta, GD Ball, DA Salomon-Kent, R Mazza, D Morisaki, T Mueller, F McNally, JG Karpova, TS AF Mehta, G. D. Ball, D. A. Salomon-Kent, R. Mazza, D. Morisaki, T. Mueller, F. McNally, J. G. Karpova, T. S. TI Single Molecule Tracking of Ace1p In Saccharomyces cerevisiae defines a characteristic residence time for non-specific interactions of transcription factors with chromatin. SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract CT Annual Meeting of the American-Society-for-Cell-Biology (ASCB) CY DEC 03-07, 2016 CL San Francisco, CA SP Amer Soc Cell Biol C1 [Mehta, G. D.; Ball, D. A.; Salomon-Kent, R.; Karpova, T. S.] NIH, Lab Receptor Biol & Gene Express, Bldg 10, Bethesda, MD 20892 USA. [Mazza, D.] Ctr Imaging Sperimentale, Milan, Italy. [Mazza, D.] Univ Vita Salute San Raffaele, Ist Sci, Osped San Raffaele, Milan, Italy. 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TI Characterization of the role of deubiquitylating enzyme USP3 in Clathrin-independent endocytosis (CIE) cargo specific trafficking SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract CT Annual Meeting of the American-Society-for-Cell-Biology (ASCB) CY DEC 03-07, 2016 CL San Francisco, CA SP Amer Soc Cell Biol C1 [Niyogi, S.; Wayt, J. L.; Williamson, C.; Donaldson, J.; Eshun-Wilson, L.] NHLBI, NIH, Bldg 10, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 EI 1939-4586 J9 MOL BIOL CELL JI Mol. Biol. Cell PY 2016 VL 27 MA P1261 PG 2 WC Cell Biology SC Cell Biology GA EN5LN UT WOS:000396047100263 ER PT J AU Parilla, J Elshazzly, ME Vaidya, K Adelstein, RS Kawamoto, S AF Parilla, J. Elshazzly, M. E. Vaidya, K. Adelstein, R. S. Kawamoto, S. TI Isoform diversity of Rbfox family proteins. SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract CT Annual Meeting of the American-Society-for-Cell-Biology (ASCB) CY DEC 03-07, 2016 CL San Francisco, CA SP Amer Soc Cell Biol C1 [Parilla, J.; Elshazzly, M. E.; Vaidya, K.; Adelstein, R. S.; Kawamoto, S.] NHLBI, NIH, Bldg 10, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 EI 1939-4586 J9 MOL BIOL CELL JI Mol. Biol. Cell PY 2016 VL 27 MA P1193 PG 2 WC Cell Biology SC Cell Biology GA EN5LN UT WOS:000396047100196 ER PT J AU Rodriguez, J Chow, CC Larson, DR AF Rodriguez, J. Chow, C. C. Larson, D. R. TI Regulation of estrogen-responsive genes in single human cells. SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract CT Annual Meeting of the American-Society-for-Cell-Biology (ASCB) CY DEC 03-07, 2016 CL San Francisco, CA SP Amer Soc Cell Biol C1 [Rodriguez, J.; Larson, D. R.] NCI, Lab Receptor Biol Gene Express, Bethesda, MD 20892 USA. [Chow, C. C.] NIDDKD, Lab Biol Modeling, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 EI 1939-4586 J9 MOL BIOL CELL JI Mol. Biol. Cell PY 2016 VL 27 MA P1176 PG 1 WC Cell Biology SC Cell Biology GA EN5LN UT WOS:000396047100179 ER PT J AU Schoborg, TA Smith, L Fagerstrom, CJ Rusan, NM AF Schoborg, T. A. Smith, L. Fagerstrom, C. J. Rusan, N. M. TI ASP suppresses microcephaly through spindle-independent pathways SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract CT Annual Meeting of the American-Society-for-Cell-Biology (ASCB) CY DEC 03-07, 2016 CL San Francisco, CA SP Amer Soc Cell Biol C1 [Schoborg, T. A.; Smith, L.; Fagerstrom, C. J.; Rusan, N. M.] NHLBI, NIH, Bldg 10, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 EI 1939-4586 J9 MOL BIOL CELL JI Mol. Biol. Cell PY 2016 VL 27 MA P1573 PG 1 WC Cell Biology SC Cell Biology GA EN5LN UT WOS:000396047100575 ER PT J AU Shin, K Lee, Y Moon, H Park, S Seo, Y Ryu, S Suh, P AF Shin, K. Lee, Y. Moon, H. Park, S. Seo, Y. Ryu, S. Suh, P. TI NSMF mediates psychological stress-induced breast cancer progression. SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract CT Annual Meeting of the American-Society-for-Cell-Biology (ASCB) CY DEC 03-07, 2016 CL San Francisco, CA SP Amer Soc Cell Biol C1 [Shin, K.; Lee, Y.; Park, S.; Seo, Y.; Suh, P.] UNIST, Sch Life Sci, Ulsan, South Korea. [Moon, H.] NIA, Neuroplast & Behav Unit, Lab Neurosci, NIH, Baltimore, MD 21224 USA. [Ryu, S.] POSTECH, Div Mol & Life Sci, Pohang, South Korea. NR 0 TC 0 Z9 0 U1 1 U2 1 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 EI 1939-4586 J9 MOL BIOL CELL JI Mol. Biol. Cell PY 2016 VL 27 MA P1129 PG 1 WC Cell Biology SC Cell Biology GA EN5LN UT WOS:000396047100134 ER PT J AU Shitara, A Milberg, O Tora, MS Ebrahim, S Weigert, R AF Shitara, A. Milberg, O. Tora, M. S. Ebrahim, S. Weigert, R. TI Molecular mechanisms of membrane remodeling during regulated secretion in live animals SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract CT Annual Meeting of the American-Society-for-Cell-Biology (ASCB) CY DEC 03-07, 2016 CL San Francisco, CA SP Amer Soc Cell Biol C1 [Shitara, A.; Tora, M. S.; Ebrahim, S.; Weigert, R.] NCI, Cellular & Mol Biol Lab, Ctr Canc Res, Bldg 37, Bethesda, MD 20892 USA. [Milberg, O.; Tora, M. S.] Natl Inst Dent & Craniofacial Res, Intracellular Membrane Trafficking Sect, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 EI 1939-4586 J9 MOL BIOL CELL JI Mol. Biol. Cell PY 2016 VL 27 MA P1452 PG 2 WC Cell Biology SC Cell Biology GA EN5LN UT WOS:000396047100453 ER PT J AU Sohn, M Balla, T AF Sohn, M. Balla, T. TI FUNCTIONAL ANALYSIS OF THE PI4P/PS TRANSFER PROPERTIES OF ORP5 AND ORP8. SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract CT Annual Meeting of the American-Society-for-Cell-Biology (ASCB) CY DEC 03-07, 2016 CL San Francisco, CA SP Amer Soc Cell Biol C1 [Sohn, M.; Balla, T.] NICHHD, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 EI 1939-4586 J9 MOL BIOL CELL JI Mol. Biol. Cell PY 2016 VL 27 MA P1362 PG 1 WC Cell Biology SC Cell Biology GA EN5LN UT WOS:000396047100363 ER PT J AU Toth, DJ Balla, T AF Toth, D. J. Balla, T. TI Deciphering the function of the two mammalian EFR3 proteins. SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract CT Annual Meeting of the American-Society-for-Cell-Biology (ASCB) CY DEC 03-07, 2016 CL San Francisco, CA SP Amer Soc Cell Biol C1 [Toth, D. J.; Balla, T.] Eunice Kennedy Shriver NICHD, Sect Mol Signal Transduct, Program Dev Neurosci, NIH, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 EI 1939-4586 J9 MOL BIOL CELL JI Mol. Biol. Cell PY 2016 VL 27 MA P1416 PG 2 WC Cell Biology SC Cell Biology GA EN5LN UT WOS:000396047100417 ER PT J AU Wayt, JL Dutta, D Donaldson, J AF Wayt, J. L. Dutta, D. Donaldson, J. TI A membrane trafficking screen to identify Clathrin-independent endocytosis machinery SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract CT Annual Meeting of the American-Society-for-Cell-Biology (ASCB) CY DEC 03-07, 2016 CL San Francisco, CA SP Amer Soc Cell Biol C1 [Wayt, J. L.; Dutta, D.; Donaldson, J.] NHLBI, NIH, Bldg 10, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 EI 1939-4586 J9 MOL BIOL CELL JI Mol. Biol. Cell PY 2016 VL 27 MA P1260 PG 2 WC Cell Biology SC Cell Biology GA EN5LN UT WOS:000396047100262 ER PT J AU Yaffe, Y Dellibovi-Ragheb, TA Chen, Y Elkabetz, Y Altan-Bonnet, N AF Yaffe, Y. Dellibovi-Ragheb, T. A. Chen, Y. Elkabetz, Y. Altan-Bonnet, N. TI The role of centrosomes in the pathogenesis of Zika virus (ZIKV)-related microcephaly SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract CT Annual Meeting of the American-Society-for-Cell-Biology (ASCB) CY DEC 03-07, 2016 CL San Francisco, CA SP Amer Soc Cell Biol C1 [Yaffe, Y.; Dellibovi-Ragheb, T. A.; Chen, Y.; Altan-Bonnet, N.] NHLBI, NIH, Bldg 10, Bethesda, MD 20892 USA. [Elkabetz, Y.] Tel Aviv Univ, Dept Cell & Dev Biol, Tel Aviv, Israel. NR 0 TC 0 Z9 0 U1 1 U2 1 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 EI 1939-4586 J9 MOL BIOL CELL JI Mol. Biol. Cell PY 2016 VL 27 MA P1071 PG 1 WC Cell Biology SC Cell Biology GA EN5LN UT WOS:000396047100077 ER PT J AU Yu, L Blatchford, K Castro, L Gao, X Plair, J Dixon, D AF Yu, L. Blatchford, K. Castro, L. Gao, X. Plair, J. Dixon, D. TI The contribution of membrane associated G protein-coupled estrogen receptor 1 in nongenomic signaling by bisphenol A. SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract CT Annual Meeting of the American-Society-for-Cell-Biology (ASCB) CY DEC 03-07, 2016 CL San Francisco, CA SP Amer Soc Cell Biol C1 [Yu, L.; Blatchford, K.; Castro, L.; Plair, J.; Dixon, D.] NIEHS, Mol Pathogenesis Grp, NTPL, DNTP,NIH,DHHS, POB 12233, Res Triangle Pk, NC 27709 USA. [Blatchford, K.] North Carolina State Univ, Raleigh, NC USA. [Gao, X.] DS Technol Inc, Morrisville, NC USA. [Plair, J.] St Augustines Univ, Raleigh, NC USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 EI 1939-4586 J9 MOL BIOL CELL JI Mol. Biol. Cell PY 2016 VL 27 MA P1419 PG 1 WC Cell Biology SC Cell Biology GA EN5LN UT WOS:000396047100420 ER PT J AU Zhao, Z Wang, S Wu, D Mikrut, SO Viscardi, V Desai, AB Oegema, K AF Zhao, Z. Wang, S. Wu, D. Mikrut, S. Ochoa Viscardi, V. Desai, A. B. Oegema, K. TI Plk1 controls PCM assembly by phosphorylating SPD-2 and SPD-5 in C. elegans. SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract CT Annual Meeting of the American-Society-for-Cell-Biology (ASCB) CY DEC 03-07, 2016 CL San Francisco, CA SP Amer Soc Cell Biol C1 [Zhao, Z.; Wang, S.; Mikrut, S. Ochoa; Viscardi, V.; Desai, A. B.; Oegema, K.] Ludwig Inst Canc Res, La Jolla, CA USA. [Wang, S.] Natl Inst Dent & Craniofacial Res, NIH, Bethesda, MD USA. [Wu, D.] Natl Inst Diabet & Digest & Kidney Dis, NIH, Bethesda, MD USA. [Mikrut, S. Ochoa; Desai, A. B.; Oegema, K.] Univ Calif San Diego, La Jolla, CA 92093 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 EI 1939-4586 J9 MOL BIOL CELL JI Mol. Biol. Cell PY 2016 VL 27 MA P1076 PG 1 WC Cell Biology SC Cell Biology GA EN5LN UT WOS:000396047100082 ER PT J AU Mikula, JM Manion, MM Maldarelli, F Suarez, LM Norman-Wheeler, JF Ober, AG Dewar, RL Kopp, JB Lane, HC Pau, AK AF Mikula, James M. Manion, Maura M. Maldarelli, Frank Suarez, Lucila M. Norman-Wheeler, Jaha F. Ober, Alex G. Dewar, Robin L. Kopp, Jeffrey B. Lane, H. Clifford Pau, Alice K. TI Tenofovir alafenamide as part of a salvage regimen in a patient with multi-drug resistant HIV and tenofovir-DF-associated renal tubulopathy SO ANTIVIRAL THERAPY LA English DT Article ID DISOPROXIL FUMARATE; NON-INFERIORITY; INFECTION; SAFETY; ADULTS; DOLUTEGRAVIR; ELVITEGRAVIR; RALTEGRAVIR; MANAGEMENT; EFFICACY AB We describe a patient with two recent episodes of tenofovir disoproxil fumarate (TDF)-associated acute kidney injury and six-class drug-resistant HIV infection who achieved and maintained viral suppression without worsening kidney function on a regimen including tenofovir alafenamide (TAF) through 48 weeks of therapy. The safety and efficacy of TAF in patients with TDF-associated renal tubulopathy and multiple drug resistant HIV has not yet been described. TAF may represent a useful option to maximally suppress HIV in patients with these complications. C1 [Mikula, James M.] Leidos Biomed Res Inc, Frederick Natl Lab Canc Res, Clin Res Directorate, Clin Monitoring Res Program, Frederick, MD USA. [Manion, Maura M.; Suarez, Lucila M.; Ober, Alex G.; Lane, H. Clifford; Pau, Alice K.] NIAID, NIH, Bethesda, MD 20892 USA. [Maldarelli, Frank] NCI, HIV Drug Resistance Program, Bethesda, MD 20892 USA. [Norman-Wheeler, Jaha F.] NIH, Clin Ctr, Bethesda, MD 20892 USA. [Dewar, Robin L.] Leidos Biomed Res Inc, Frederick Natl Lab Canc Res, Appl & Dev Res Directorate, Frederick, MD USA. [Kopp, Jeffrey B.] NIDDK, NIH, Bethesda, MD USA. RP Pau, AK (reprint author), NIAID, NIH, Bethesda, MD 20892 USA. EM apau@niaid.nih.gov FU National Institute of Allergy and Infectious Diseases; NIDDK Intramural Research Program; National Cancer Institute, National Institutes of Health (NIH) [HHSN261200800001E] FX We would like to acknowledge Vasilios Pyrgos (Montgomery Infectious Diseases Associates, Silver Spring, MD, USA) for referring the patient to our protocol, and the patient for his participation in the study. The research was supported in part by the National Institute of Allergy and Infectious Diseases and the NIDDK Intramural Research Program. This project has also been funded in part with federal funds from the National Cancer Institute, National Institutes of Health (NIH), under Contract number HHSN261200800001E. The content of this publication does not necessarily reflect the views or policies of the Department of Health and Human Services, nor does mention of trade names, commercial products, or organizations imply endorsement by the US Government. Tenofovir alafenamide (25 mg)/emtricitabine (200 mg) combination tablet was provided by Gilead Sciences, Foster City, CA, USA. NR 21 TC 0 Z9 0 U1 1 U2 1 PU INT MEDICAL PRESS LTD PI LONDON PA 2-4 IDOL LANE, LONDON EC3R 5DD, ENGLAND SN 1359-6535 J9 ANTIVIR THER JI Antivir. Ther. PY 2016 VL 21 IS 6 BP 553 EP 558 DI 10.3851/IMP3040 PG 6 WC Infectious Diseases; Pharmacology & Pharmacy; Virology SC Infectious Diseases; Pharmacology & Pharmacy; Virology GA EN6BN UT WOS:000396089600011 PM 26954372 ER PT J AU Lin, B He, SS Yim, HJ Liang, TJ Hu, ZY AF Lin, Billy He, Shanshan Yim, Hyung Joon Liang, T. Jake Hu, Zongyi TI Evaluation of antiviral drug synergy in an infectious HCV system SO ANTIVIRAL THERAPY LA English DT Article ID HEPATITIS-C-VIRUS; INTERFERON-ALPHA; NS5A INHIBITOR; LIFE-CYCLE; RESISTANCE; REPLICATION; PROTEASE; ENTRY; COMBINATION; THERAPIES AB Background: Direct-acting antivirals (DAAs) have greatly improved the treatment of HCV infection. To improve response and prevent resistance, combination regimens have been the focus of clinical development. Regimens are often first assessed in vitro, with most combination studies to date using subgenomic replicon systems, which do not replicate the complete HCV life cycle and preclude study of entry and assembly inhibitors. Infectious full-length HCV systems have been developed and are being used to test drug efficacy. Methods: Using cell-based HCV Con1b replicon and an infectious full-length HCV (HCVcc-Luc) infection system, we systematically tested the synergy, additivity or antagonism of combinations of protease, NS5A and nucleotide NS5B inhibitor classes as well as the combination of these DAAs with host-targeting agent cyclosporin A or non-antibody entry inhibitor (S)-chlorcyclizine. Two computational software packages, MacSynergyII and CalcuSyn, were used for data analysis. Results: Combinations between different classes showed good consistency across the two viral assay systems and two software platforms. Combinations between NS5A and nucleotide NS5B inhibitors were synergistic, while combinations of protease inhibitors with the other two classes were additive to slightly antagonistic. As expected, combinations of antivirals of the same class were additive. Combination studies between these DAA classes and cyclosporin A or (S)-chlorcyclizine demonstrated additive to synergistic effects and highly synergistic effects, respectively. Combinations of these drugs did not show any added or unexpected cytotoxicity. Conclusions: Our results show that in vitro combination studies of anti-HCV DAAs in the HCVcc system may provide useful guidance for drug combination designs in clinical studies. We also demonstrate that these DAAs in combination with host-targeting agents or entry inhibitors may improve HCV treatment response. C1 [Lin, Billy; He, Shanshan; Yim, Hyung Joon; Liang, T. Jake; Hu, Zongyi] NIDDK, Liver Dis Branch, NIH, Bethesda, MD 20892 USA. RP Hu, ZY (reprint author), NIDDK, Liver Dis Branch, NIH, Bethesda, MD 20892 USA. EM zh1g@nih.gov FU National Institute of Diabetes and Digestive and Kidney Diseases FX Funding was provided by the Intramural Research Program of the National Institute of Diabetes and Digestive and Kidney Diseases. NR 35 TC 0 Z9 0 U1 0 U2 0 PU INT MEDICAL PRESS LTD PI LONDON PA 2-4 IDOL LANE, LONDON EC3R 5DD, ENGLAND SN 1359-6535 J9 ANTIVIR THER JI Antivir. Ther. PY 2016 VL 21 IS 7 BP 595 EP 603 DI 10.3851/IMP3044 PG 9 WC Infectious Diseases; Pharmacology & Pharmacy; Virology SC Infectious Diseases; Pharmacology & Pharmacy; Virology GA EN6BO UT WOS:000396089700005 PM 27035622 ER PT J AU Adams, G Logue, J Lippincott-Schwartz, J Waterman, CM AF Adams, G., Jr. Logue, J. Lippincott-Schwartz, J. Waterman, C. M. TI Characterization of organelle localization and dynamics during leader-bleb based motility of melanoma cells under non-adhesive confinement. SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract CT Annual Meeting of the American-Society-for-Cell-Biology (ASCB) CY DEC 03-07, 2016 CL San Francisco, CA SP Amer Soc Cell Biol C1 [Adams, G., Jr.; Waterman, C. M.] NHLBI, NIH, Bldg 10, Bethesda, MD 20892 USA. [Logue, J.] Albany Med Ctr, RCCB, Albany, NY USA. [Lippincott-Schwartz, J.] HHMI Janelia Res Campus, Ashburn, VA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 EI 1939-4586 J9 MOL BIOL CELL JI Mol. Biol. Cell PY 2016 VL 27 MA P2145 PG 2 WC Cell Biology SC Cell Biology GA EN5LO UT WOS:000396047200446 ER PT J AU Adikaram, PR Zhang, J Pandey, M Simonds, WF AF Adikaram, P. R. Zhang, J. Pandey, M. Simonds, W. F. TI Identification of Novel Parafibromin Protein Partners Using A Proteomic Approach. SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract CT Annual Meeting of the American-Society-for-Cell-Biology (ASCB) CY DEC 03-07, 2016 CL San Francisco, CA SP Amer Soc Cell Biol C1 [Adikaram, P. R.; Zhang, J.; Pandey, M.; Simonds, W. F.] NIDDK, NIH, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 EI 1939-4586 J9 MOL BIOL CELL JI Mol. Biol. Cell PY 2016 VL 27 MA P301 PG 2 WC Cell Biology SC Cell Biology GA EN5LM UT WOS:000396046900300 ER PT J AU Akan, I Love, D Hanover, JA AF Akan, I. Love, D. Hanover, J. A. TI Drosophila O-GlcNAcase Deletion Globally Perturbs Chromatin O-GlcNAcylation SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract CT Annual Meeting of the American-Society-for-Cell-Biology (ASCB) CY DEC 03-07, 2016 CL San Francisco, CA SP Amer Soc Cell Biol C1 [Akan, I.; Love, D.; Hanover, J. A.] NIDDK, LCMB, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 EI 1939-4586 J9 MOL BIOL CELL JI Mol. Biol. Cell PY 2016 VL 27 MA P2010 PG 2 WC Cell Biology SC Cell Biology GA EN5LO UT WOS:000396047200312 ER PT J AU Alexander, CJ Hammer, JA AF Alexander, C. J. Hammer, J. A. TI Differentiation of Mouse Embryonic Stem Cells into Purkinje Neurons. SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract CT Annual Meeting of the American-Society-for-Cell-Biology (ASCB) CY DEC 03-07, 2016 CL San Francisco, CA SP Amer Soc Cell Biol C1 [Alexander, C. J.; Hammer, J. A.] NHLBI, CBPC, Bethsda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 EI 1939-4586 J9 MOL BIOL CELL JI Mol. Biol. Cell PY 2016 VL 27 MA P481 PG 1 WC Cell Biology SC Cell Biology GA EN5LM UT WOS:000396046900480 ER PT J AU Baird, MA Billington, N Wang, A Adelstein, RS Sellers, JR Fischer, RS Waterman, CM AF Baird, M. A. Billington, N. Wang, A. Adelstein, R. S. Sellers, J. R. Fischer, R. S. Waterman, C. M. TI Local pulsatile contractions are an intrinsic property of the myosin 2A motor in the cortex of adherent cells. SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract CT Annual Meeting of the American-Society-for-Cell-Biology (ASCB) CY DEC 03-07, 2016 CL San Francisco, CA SP Amer Soc Cell Biol C1 [Baird, M. A.; Billington, N.; Wang, A.; Adelstein, R. S.; Sellers, J. R.; Fischer, R. S.; Waterman, C. M.] NHLBI, NIH, Bldg 10, Bethesda, MD 20892 USA. [Wang, A.] Hunan Agr Univ, Coll Vet Med, Changsha, Hunan, Peoples R China. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 EI 1939-4586 J9 MOL BIOL CELL JI Mol. Biol. Cell PY 2016 VL 27 MA P952 PG 1 WC Cell Biology SC Cell Biology GA EN5LM UT WOS:000396046900951 ER PT J AU Beach, JR Bruun, KS Shao, L Li, D Swider, Z Remmert, K Zhang, Y Conti, MA Adelstein, RS Rusan, NM Betzig, E Hammer, JA AF Beach, J. R. Bruun, K. S. Shao, L. Li, D. Swider, Z. Remmert, K. Zhang, Y. Conti, M. A. Adelstein, R. S. Rusan, N. M. Betzig, E. Hammer, J. A. TI Non-Muscle Myosin 2 Filament Assembly by Grouped Expansion of Myosin Later than Initial Nucleation (GrEMLIN) SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract CT Annual Meeting of the American-Society-for-Cell-Biology (ASCB) CY DEC 03-07, 2016 CL San Francisco, CA SP Amer Soc Cell Biol C1 [Beach, J. R.; Bruun, K. S.; Swider, Z.; Remmert, K.; Hammer, J. A.] NHLBI, Cell Biol & Physiol Ctr, Bldg 10, Bethesda, MD 20892 USA. [Shao, L.; Li, D.; Betzig, E.] Howard Hughes Med Inst, Janelia Res Campus, Ashburn, VA USA. [Zhang, Y.; Conti, M. A.; Adelstein, R. S.; Rusan, N. M.] NHLBI, Lab Mol Cardiol, Bldg 10, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 EI 1939-4586 J9 MOL BIOL CELL JI Mol. Biol. Cell PY 2016 VL 27 MA P1712 PG 2 WC Cell Biology SC Cell Biology GA EN5LO UT WOS:000396047200013 ER PT J AU Becker, AK Sickler, PS Jimenez, EA Walsh, S AF Becker, A. K. Sickler, P. S. Jimenez, E. A. Walsh, S. TI Assessment of a semester-long course-based undergraduate research experience examining zebrafish regeneration. SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract CT Annual Meeting of the American-Society-for-Cell-Biology (ASCB) CY DEC 03-07, 2016 CL San Francisco, CA SP Amer Soc Cell Biol C1 [Becker, A. K.; Sickler, P. S.; Walsh, S.] Rollins Coll, Biol, Winter Pk, FL 32789 USA. [Jimenez, E. A.] NIH, Natl Ctr Human Genome Res, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 EI 1939-4586 J9 MOL BIOL CELL JI Mol. Biol. Cell PY 2016 VL 27 MA P837 PG 1 WC Cell Biology SC Cell Biology GA EN5LM UT WOS:000396046900836 ER PT J AU Booth, DG Beckett, A Molina, O Samejima, I Larionov, V Kouprina, N Prior, I Earnshaw, WC AF Booth, D. G. Beckett, A. Molina, O. Samejima, I. Larionov, V. Kouprina, N. Prior, I. Earnshaw, W. C. TI 3D-CLEM reveals that a major portion of mitotic chromosomes is not chromatin SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract CT Annual Meeting of the American-Society-for-Cell-Biology (ASCB) CY DEC 03-07, 2016 CL San Francisco, CA SP Amer Soc Cell Biol C1 [Booth, D. G.] Univ Edinburgh, Ctr Regenerat Med, Edinburgh, Midlothian, Scotland. [Booth, D. G.; Molina, O.; Samejima, I.; Earnshaw, W. C.] Univ Edinburgh, Wellcome Trust Ctr Cell Biol, Edinburgh, Midlothian, Scotland. [Beckett, A.; Prior, I.] Univ Liverpool, Translat Med, Liverpool, Merseyside, England. [Larionov, V.; Kouprina, N.] NCI, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 EI 1939-4586 J9 MOL BIOL CELL JI Mol. Biol. Cell PY 2016 VL 27 MA P235 PG 1 WC Cell Biology SC Cell Biology GA EN5LM UT WOS:000396046900234 ER PT J AU Bruun, S Beach, J Hammer, JA Remmert, K AF Bruun, K. S. Beach, J. Hammer, J. A. Remmert, K. TI Re-examining the Roles of Myosin 18A and Actin in Golgi Morphology. SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract CT Annual Meeting of the American-Society-for-Cell-Biology (ASCB) CY DEC 03-07, 2016 CL San Francisco, CA SP Amer Soc Cell Biol C1 [Bruun, K. S.; Beach, J.; Hammer, J. A.; Remmert, K.] NHLBI, NIH, Bldg 10, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 EI 1939-4586 J9 MOL BIOL CELL JI Mol. Biol. Cell PY 2016 VL 27 MA P958 PG 1 WC Cell Biology SC Cell Biology GA EN5LM UT WOS:000396046900957 ER PT J AU Christensen, R Bokinsky, A Santella, A Wu, Y Marquina, J Kovacevic, I Kumar, A McCreedy, E Mohler, W Colon-Ramos, DA Bao, Z Shroff, H AF Christensen, R. Bokinsky, A. Santella, A. Wu, Y. Marquina, J. Kovacevic, I. Kumar, A. McCreedy, E. Mohler, W. Colon-Ramos, D. A. Bao, Z. Shroff, H. TI A combined imaging and software approach for analyzing C. elegans embryo development. SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract CT Annual Meeting of the American-Society-for-Cell-Biology (ASCB) CY DEC 03-07, 2016 CL San Francisco, CA SP Amer Soc Cell Biol C1 [Christensen, R.; Wu, Y.; Kumar, A.; Shroff, H.] Natl Inst Biomed Imaging & Bioengn, NIH, Bethesda, MD USA. [Bokinsky, A.; McCreedy, E.] NIH, Ctr Informat Technol, Bldg 10, Bethesda, MD 20892 USA. [Santella, A.; Kovacevic, I.; Bao, Z.] Sloan Kettering Inst, Dev Biol Program, New York, NY USA. [Marquina, J.; Colon-Ramos, D. A.] Yale Univ, Dept Cell Biol, New Haven, CT USA. [Mohler, W.] Univ Connecticut, Ctr Hlth, Dept Genet & Dev Biol, Farmington, CT USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 EI 1939-4586 J9 MOL BIOL CELL JI Mol. Biol. Cell PY 2016 VL 27 MA P44 PG 1 WC Cell Biology SC Cell Biology GA EN5LM UT WOS:000396046900045 ER PT J AU Citron, R Kelly, M Rusan, NM Huang, B Agard, DA AF Citron, R. Kelly, M. Rusan, N. M. Huang, B. Agard, D. A. TI A Conserved Motif in Centrosomin's Carboxyl Terminus, Sufficient for PCM localization, Interacts Directly with Two Binding Partners. SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract CT Annual Meeting of the American-Society-for-Cell-Biology (ASCB) CY DEC 03-07, 2016 CL San Francisco, CA SP Amer Soc Cell Biol C1 [Citron, R.; Kelly, M.; Huang, B.; Agard, D. A.] Univ Calif San Francisco, Biochem & Biophys, San Francisco, CA 94143 USA. [Rusan, N. M.] NHLBI, Physiol Ctr, Bldg 10, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 EI 1939-4586 J9 MOL BIOL CELL JI Mol. Biol. Cell PY 2016 VL 27 MA P990 PG 1 WC Cell Biology SC Cell Biology GA EN5LM UT WOS:000396046900989 ER PT J AU Dobrinskikh, E Al-Juboori, SI Lewis, L Zerfas, P Blaine, J AF Dobrinskikh, E. Al-Juboori, S. I. Lewis, L. Zerfas, P. Blaine, J. TI Intracellular Calcium Modulates Mitochondrial Shape and Activity in Podocytes SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract CT Annual Meeting of the American-Society-for-Cell-Biology (ASCB) CY DEC 03-07, 2016 CL San Francisco, CA SP Amer Soc Cell Biol C1 [Dobrinskikh, E.; Lewis, L.; Blaine, J.] Univ Colorado Denver, Dept Med, Aurora, CO USA. [Al-Juboori, S. I.] Univ Colorado Denver, Dept Elect Engn, Aurora, CO USA. [Zerfas, P.] NIH, Electron Core Microscopy Facil, Bldg 10, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 EI 1939-4586 J9 MOL BIOL CELL JI Mol. Biol. Cell PY 2016 VL 27 MA P530 PG 1 WC Cell Biology SC Cell Biology GA EN5LM UT WOS:000396046900529 ER PT J AU Duenas, BPR Allgood, SC Noll, RR Yu, X Qiu, J Machner, M LaBaer, J Neunuebel, R AF Duenas, B. P. Romero Allgood, S. C. Noll, R. R. Yu, X. Qiu, J. Machner, M. LaBaer, J. Neunuebel, R. TI Novel human targets of L pneumophila effector protein AnkX identified by NAPPA protein arrays. SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract CT Annual Meeting of the American-Society-for-Cell-Biology (ASCB) CY DEC 03-07, 2016 CL San Francisco, CA SP Amer Soc Cell Biol C1 [Duenas, B. P. Romero; Allgood, S. C.; Noll, R. R.; Neunuebel, R.] Univ Delaware, Biol Sci, Newark, DE USA. [Yu, X.] Beijing Inst Radiat Med, Natl Ctr Prot Sci Beijing, Beijing Proteome Res Ctr, Beijing, Peoples R China. [Qiu, J.; LaBaer, J.] Arizona State Univ, Biodesign Inst, Virginia G Piper Ctr Personalized Diagnost, Tempe, AZ USA. [Machner, M.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, NIH, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 EI 1939-4586 J9 MOL BIOL CELL JI Mol. Biol. Cell PY 2016 VL 27 MA P2425 PG 1 WC Cell Biology SC Cell Biology GA EN5LO UT WOS:000396047200725 ER PT J AU Feliciano, D Obara, CJ Rieckhoff, E Lee, L Rakusova, H Afonso, O Adams, G Lippincott-Schwartz, J AF Feliciano, D. Obara, C. J. Rieckhoff, E. Lee, L. Rakusova, H. Afonso, O. Adams, G. Lippincott-Schwartz, J. TI Cytoplasmic and Organelle Intermixing upon Cell-to-Cell Fusion. SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract CT Annual Meeting of the American-Society-for-Cell-Biology (ASCB) CY DEC 03-07, 2016 CL San Francisco, CA SP Amer Soc Cell Biol C1 [Feliciano, D.; Obara, C. J.; Rieckhoff, E.; Lee, L.; Rakusova, H.; Afonso, O.; Adams, G.; Lippincott-Schwartz, J.] Marine Biol Lab, Physiol Course, Woods Hole, MA 02543 USA. [Feliciano, D.; Obara, C. J.; Lippincott-Schwartz, J.] Howard Hughes Med Inst, Janelia Res Campus, Ashburn, VA USA. [Rieckhoff, E.] Max Planck Inst Phys Komplexer Syst, Mol Cell Biol & Genet, Dresden, Germany. [Lee, L.] Harvard Univ, Appl Phys Dept, Cambridge, MA 02138 USA. [Rakusova, H.] McGill Univ, Dept Plant Syst Biol, Macdonald Campus, Montreal, PQ, Canada. [Afonso, O.] Inst Mol & Cell Biol, IBMC INEB, Oporto, Portugal. [Adams, G.] NHLBI, NIH, Bldg 10, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 EI 1939-4586 J9 MOL BIOL CELL JI Mol. Biol. Cell PY 2016 VL 27 MA P2143 PG 2 WC Cell Biology SC Cell Biology GA EN5LO UT WOS:000396047200444 ER PT J AU Fischer, RS Sun, X Losert, W Fourkas, JT Waterman, CM AF Fischer, R. S. Sun, X. Losert, W. Fourkas, J. T. Waterman, C. M. TI Topology Regulates Cell Polarity via Spatial Distribution of Both Adhesions and Actomyosin Contraction. SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract CT Annual Meeting of the American-Society-for-Cell-Biology (ASCB) CY DEC 03-07, 2016 CL San Francisco, CA SP Amer Soc Cell Biol C1 [Fischer, R. S.; Waterman, C. M.] NHLBI, Cell Biol & Physiol, Bldg 10, Bethesda, MD 20892 USA. [Sun, X.; Fourkas, J. T.] Univ Maryland, Chem, College Pk, MD 20742 USA. [Losert, W.] Univ Maryland, Phys, College Pk, MD 20742 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 EI 1939-4586 J9 MOL BIOL CELL JI Mol. Biol. Cell PY 2016 VL 27 MA P2117 PG 2 WC Cell Biology SC Cell Biology GA EN5LO UT WOS:000396047200418 ER PT J AU George, A Boulanger, C Brisken, C Smith, GH AF George, A. Boulanger, C. Brisken, C. Smith, G. H. TI Amphiregulin is dispensable for redirection of non-mammary cells to a mammary stem cell fate in vivo. SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract CT Annual Meeting of the American-Society-for-Cell-Biology (ASCB) CY DEC 03-07, 2016 CL San Francisco, CA SP Amer Soc Cell Biol C1 [George, A.; Boulanger, C.; Smith, G. H.] NCI, Basic Res Lab, Bethesda, MD 20892 USA. [Brisken, C.] Swiss Inst Expt Res, Mol Oncol, Lausanne, Switzerland. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 EI 1939-4586 J9 MOL BIOL CELL JI Mol. Biol. Cell PY 2016 VL 27 MA P782 PG 1 WC Cell Biology SC Cell Biology GA EN5LM UT WOS:000396046900781 ER PT J AU Gurel, PS Kim, LY Omabegho, T Bryant, Z Alushin, GM AF Gurel, P. S. Kim, L. Y. Omabegho, T. Bryant, Z. Alushin, G. M. TI High-resolution structural characterization of the myosin VI-F-actin interface during the force generation cycle. SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract CT Annual Meeting of the American-Society-for-Cell-Biology (ASCB) CY DEC 03-07, 2016 CL San Francisco, CA SP Amer Soc Cell Biol C1 [Gurel, P. S.; Kim, L. Y.; Alushin, G. M.] NHLBI, Cell Biol & Physiol Ctr, Bldg 10, Bethesda, MD 20892 USA. [Omabegho, T.; Bryant, Z.] Stanford Univ, Sch Med, Dept Bioengn, Stanford, CA 94305 USA. [Omabegho, T.; Bryant, Z.] Stanford Univ, Sch Med, Dept Struct Biol, Stanford, CA 94305 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 EI 1939-4586 J9 MOL BIOL CELL JI Mol. Biol. Cell PY 2016 VL 27 MA P957 PG 1 WC Cell Biology SC Cell Biology GA EN5LM UT WOS:000396046900956 ER PT J AU Heimsath, EG Yim, Y Mustapha, M Hammer, JA Cheney, RE AF Heimsath, E. G., Jr. Yim, Y. Mustapha, M. Hammer, J. A. Cheney, R. E. TI Cellular and Organismal Function of Myosin-X. SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract CT Annual Meeting of the American-Society-for-Cell-Biology (ASCB) CY DEC 03-07, 2016 CL San Francisco, CA SP Amer Soc Cell Biol C1 [Heimsath, E. G., Jr.; Cheney, R. E.] UNC Sch Med, Cell Biol Physiol, Chapel Hill, NC USA. [Yim, Y.; Hammer, J. A.] NHLBI, NIH, Bldg 10, Bethesda, MD 20892 USA. [Mustapha, M.] Stanford Univ, Dept Otolaryngol Head Neck Surg, Stanford, CA 94305 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 EI 1939-4586 J9 MOL BIOL CELL JI Mol. Biol. Cell PY 2016 VL 27 MA P950 PG 2 WC Cell Biology SC Cell Biology GA EN5LM UT WOS:000396046900949 ER PT J AU Jang, S Tandon, M Riveros, PP Zheng, C Alevizos, I AF Jang, S. Tandon, M. Riveros, P. Perez Zheng, C. Alevizos, I. TI Regulation of Interferon Signaling by a Calcium-induced miRNA in Primary Human Salivary Gland Epithelial Cells. SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract CT Annual Meeting of the American-Society-for-Cell-Biology (ASCB) CY DEC 03-07, 2016 CL San Francisco, CA SP Amer Soc Cell Biol C1 [Jang, S.; Tandon, M.; Riveros, P. Perez; Zheng, C.; Alevizos, I.] NIDCR, NIH, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 EI 1939-4586 J9 MOL BIOL CELL JI Mol. Biol. Cell PY 2016 VL 27 MA P576 PG 1 WC Cell Biology SC Cell Biology GA EN5LM UT WOS:000396046900575 ER PT J AU Jaumouille, V Liu, T Betzig, E Waterman, CM AF Jaumouille, V. Liu, T. Betzig, E. Waterman, C. M. TI beta 2 integrins mediate the formation of a focal adhesion-like cytoskeleton and signaling platform during phagocytosis. SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract CT Annual Meeting of the American-Society-for-Cell-Biology (ASCB) CY DEC 03-07, 2016 CL San Francisco, CA SP Amer Soc Cell Biol C1 [Jaumouille, V.; Waterman, C. M.] NHLBI, NIH, Bldg 10, Bethesda, MD 20892 USA. [Liu, T.; Betzig, E.] Howard Hughes Med Inst, Janelia Res Campus, Ashburn, VA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 EI 1939-4586 J9 MOL BIOL CELL JI Mol. Biol. Cell PY 2016 VL 27 MA P103 PG 2 WC Cell Biology SC Cell Biology GA EN5LM UT WOS:000396046900104 ER PT J AU Jung, G Hammer, JA AF Jung, G. Hammer, J. A. TI Characterization of CARMIL-GAP, a Dictyostelium CARMIL isoform harboring a GTPase activating domain for Rac. SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract CT Annual Meeting of the American-Society-for-Cell-Biology (ASCB) CY DEC 03-07, 2016 CL San Francisco, CA SP Amer Soc Cell Biol C1 [Jung, G.; Hammer, J. A.] NHLBI, CBPC, NIH, Bldg 10, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 EI 1939-4586 J9 MOL BIOL CELL JI Mol. Biol. Cell PY 2016 VL 27 MA P80 PG 1 WC Cell Biology SC Cell Biology GA EN5LM UT WOS:000396046900081 ER PT J AU Lan, T Su, X Tseng, Y AF Lan, T. Su, X. Tseng, Y. TI Displacement correlations between a single cell and its nucleus effectively link subcellular activities and motility in cell migration analysis SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract CT Annual Meeting of the American-Society-for-Cell-Biology (ASCB) CY DEC 03-07, 2016 CL San Francisco, CA SP Amer Soc Cell Biol C1 [Lan, T.; Su, X.; Tseng, Y.] Dept Chem Engn, Gainesville, FL USA. [Tseng, Y.] Inst Cell Tissue Sci & Engn, Gainesville, FL USA. [Tseng, Y.] NCI, Phys Sci Oncol Ctr, Gainesville, FL USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 EI 1939-4586 J9 MOL BIOL CELL JI Mol. Biol. Cell PY 2016 VL 27 MA P2261 PG 1 WC Cell Biology SC Cell Biology GA EN5LO UT WOS:000396047200561 ER PT J AU Lee, HT Kim, LY Sarker, M Lu, M Alushin, GM Burridge, K Campbell, SL AF Lee, H. T. Kim, L. Y. Sarker, M. Lu, M. Alushin, G. M. Burridge, K. Campbell, S. L. TI Role of metavinculin in actin reorganization and force transmission SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract CT Annual Meeting of the American-Society-for-Cell-Biology (ASCB) CY DEC 03-07, 2016 CL San Francisco, CA SP Amer Soc Cell Biol C1 [Lee, H. T.; Sarker, M.; Lu, M.; Campbell, S. L.] Univ North Carolina Chapel Hill, Biophys & Biochem, Chapel Hill, NC USA. [Kim, L. Y.; Alushin, G. M.] NHLBI, Cell Biol & Physiol Ctr, NIH, Bldg 10, Bethesda, MD 20892 USA. [Burridge, K.] Univ North Carolina Chapel Hill, Cell Biol & Physiol, Chapel Hill, NC USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 EI 1939-4586 J9 MOL BIOL CELL JI Mol. Biol. Cell PY 2016 VL 27 MA P909 PG 1 WC Cell Biology SC Cell Biology GA EN5LM UT WOS:000396046900908 ER PT J AU Lopez, MP Shine, W Calderwood, DA Waterman, CM AF Lopez, M. Preciado Shine, W. Calderwood, D. A. Waterman, C. M. TI Filamin, migfilin and kindlin form a link between the extracellular matrix and the actin cytoskeleton at mature focal adhesions. SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract CT Annual Meeting of the American-Society-for-Cell-Biology (ASCB) CY DEC 03-07, 2016 CL San Francisco, CA SP Amer Soc Cell Biol C1 [Lopez, M. Preciado] NHLBI, NIH, Bldg 10, Bethesda, MD 20892 USA. [Shine, W.; Calderwood, D. A.; Waterman, C. M.] Yale Univ, Sch Med, New Haven, CT USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 EI 1939-4586 J9 MOL BIOL CELL JI Mol. Biol. Cell PY 2016 VL 27 MA P2249 PG 1 WC Cell Biology SC Cell Biology GA EN5LO UT WOS:000396047200549 ER PT J AU Ma, X Uchida, Y Mukoyama, Y Adelstein, RS AF Ma, X. Uchida, Y. Mukoyama, Y. Adelstein, R. S. TI The Role of Nonmuscle Myosin II in Vascular Formation. SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract CT Annual Meeting of the American-Society-for-Cell-Biology (ASCB) CY DEC 03-07, 2016 CL San Francisco, CA SP Amer Soc Cell Biol C1 [Ma, X.; Uchida, Y.; Mukoyama, Y.; Adelstein, R. S.] NHLBI, Genet Dev Biol Ctr, NIH, Bldg 10, Bethesda, MD 20892 USA. FU Division of Intramural Research, NHLBI FX This research was supported by the Division of Intramural Research, NHLBI. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 EI 1939-4586 J9 MOL BIOL CELL JI Mol. Biol. Cell PY 2016 VL 27 MA P949 PG 2 WC Cell Biology SC Cell Biology GA EN5LM UT WOS:000396046900948 ER PT J AU MacTaggart, B Bowen, C Chong, JX Bamshad, MJ Ma, X Adelstein, RS AF MacTaggart, B. Bowen, C. Chong, J. X. Bamshad, M. J. Ma, X. Adelstein, R. S. TI A role for non-muscle myosin 2B in congenital heart disease: Identifying genetic variants in Pentalogy of Cantrell using whole exome sequencing. SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract CT Annual Meeting of the American-Society-for-Cell-Biology (ASCB) CY DEC 03-07, 2016 CL San Francisco, CA SP Amer Soc Cell Biol C1 [MacTaggart, B.; Bowen, C.; Ma, X.; Adelstein, R. S.] NHLBI, Bldg 10, Bethesda, MD 20892 USA. [Chong, J. X.; Bamshad, M. J.] Univ Washington, Ctr Mendelian Genom, Seattle, WA 98195 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 EI 1939-4586 J9 MOL BIOL CELL JI Mol. Biol. Cell PY 2016 VL 27 MA P945 PG 1 WC Cell Biology SC Cell Biology GA EN5LM UT WOS:000396046900944 ER PT J AU Markley, RL Williamson, DR Katkere, B Dewan, KK Shay, AE Carlson, BA Prabhu, KS Kirimanjeswara, GS AF Markley, R. L. Williamson, D. R. Katkere, B. Dewan, K. K. Shay, A. E. Carlson, B. A. Prabhu, K. S. Kirimanjeswara, G. S. TI Macrophage selenoproteins restrict intracellular replication of Francisella tularensis SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract CT Annual Meeting of the American-Society-for-Cell-Biology (ASCB) CY DEC 03-07, 2016 CL San Francisco, CA SP Amer Soc Cell Biol C1 [Markley, R. L.; Williamson, D. R.; Katkere, B.; Dewan, K. K.; Shay, A. E.; Prabhu, K. S.; Kirimanjeswara, G. S.] Penn State Univ, Dept Vet & Biomed Sci, University Pk, PA 16802 USA. [Carlson, B. A.] NCI, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 EI 1939-4586 J9 MOL BIOL CELL JI Mol. Biol. Cell PY 2016 VL 27 MA P2418 PG 2 WC Cell Biology SC Cell Biology GA EN5LO UT WOS:000396047200718 ER PT J AU McLamarrah, TA Buster, DW Boese, C Hollingsworth, N Brian, GJ Rusan, NM Brownlee, C Rogers, GC AF McLamarrah, T. A. Buster, D. W. Boese, C. Hollingsworth, N. Brian, G. J. Rusan, N. M. Brownlee, C. Rogers, G. C. TI Plk4 phosphorylates Ana2 to block association and inhibit centriole duplication SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract CT Annual Meeting of the American-Society-for-Cell-Biology (ASCB) CY DEC 03-07, 2016 CL San Francisco, CA SP Amer Soc Cell Biol C1 [McLamarrah, T. A.; Buster, D. W.; Boese, C.; Hollingsworth, N.; Brownlee, C.; Rogers, G. C.] Univ Arizona, Canc Biol, Tucson, AZ USA. [Brian, G. J.; Rusan, N. M.] NHLBI, NIH, Bldg 10, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 EI 1939-4586 J9 MOL BIOL CELL JI Mol. Biol. Cell PY 2016 VL 27 MA P206 PG 1 WC Cell Biology SC Cell Biology GA EN5LM UT WOS:000396046900206 ER PT J AU Murugesan, S Hong, J Yi, J Li, D Beach, J Shao, L Wu, X Betzig, E Hammer, JA AF Murugesan, S. Hong, J. Yi, J. Li, D. Beach, J. Shao, L. Wu, X. Betzig, E. Hammer, J. A. TI Formin-generated actomyosin arcs propel T cell receptor microcluster movement at the immune synapse. SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract CT Annual Meeting of the American-Society-for-Cell-Biology (ASCB) CY DEC 03-07, 2016 CL San Francisco, CA SP Amer Soc Cell Biol C1 [Murugesan, S.; Hong, J.; Yi, J.; Beach, J.; Wu, X.; Hammer, J. A.] NIH, Cell Biol & Physiol Ctr, Bldg 10, Bethesda, MD 20892 USA. [Li, D.; Shao, L.; Betzig, E.] HHMI, Janelia Res Campus, Ashburn, VA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 EI 1939-4586 J9 MOL BIOL CELL JI Mol. Biol. Cell PY 2016 VL 27 MA P87 PG 2 WC Cell Biology SC Cell Biology GA EN5LM UT WOS:000396046900088 ER PT J AU Nixon-Abell, J Obara, CJ Weigel, AV Li, D Legant, WR Xu, C Pasolli, H Harvey, K Hess, HF Betzig, E Blackstone, CD Lippincott-Schwartz, J AF Nixon-Abell, J. Obara, C. J. Weigel, A. V. Li, D. Legant, W. R. Xu, C. Pasolli, H. Harvey, K. Hess, H. F. Betzig, E. Blackstone, C. D. Lippincott-Schwartz, J. TI Increased spatiotemporal resolution reveals highly dynamic dense tubular matrices in the peripheral ER. SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract CT Annual Meeting of the American-Society-for-Cell-Biology (ASCB) CY DEC 03-07, 2016 CL San Francisco, CA SP Amer Soc Cell Biol C1 [Nixon-Abell, J.; Harvey, K.] UCL, Dept Pharmacol, Sch Pharm, London, England. [Nixon-Abell, J.; Blackstone, C. D.] NINDS, Cell Biol Sect, Bldg 36,Rm 4D04, Bethesda, MD 20892 USA. [Obara, C. J.; Weigel, A. V.; Lippincott-Schwartz, J.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Sect Organelle Biol, Bethesda, MD USA. [Obara, C. J.; Weigel, A. V.; Li, D.; Legant, W. R.; Xu, C.; Pasolli, H.; Hess, H. F.; Betzig, E.; Lippincott-Schwartz, J.] Janelia Res Campus, Howard Hughes Med Inst, Ashburn, VA USA. [Li, D.] Chinese Acad Sci, Inst Biophys, Beijing, Peoples R China. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 EI 1939-4586 J9 MOL BIOL CELL JI Mol. Biol. Cell PY 2016 VL 27 MA P2139 PG 1 WC Cell Biology SC Cell Biology GA EN5LO UT WOS:000396047200440 ER PT J AU Olson, MG Sturgill, DM Wangsa, D Ried, T Quenet, D Dalal, Y AF Olson, M. G. Sturgill, D. M. Wangsa, D. Ried, T. Quenet, D. Dalal, Y. TI Investigating the role of centromeric transcription in the maintenance of human centromeres SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract CT Annual Meeting of the American-Society-for-Cell-Biology (ASCB) CY DEC 03-07, 2016 CL San Francisco, CA SP Amer Soc Cell Biol C1 [Olson, M. G.; Sturgill, D. M.; Quenet, D.; Dalal, Y.] NCI, Lab Receptor Biol & Gene Express, Bethesda, MD 20892 USA. [Wangsa, D.; Ried, T.] NCI, Genet Branch, Bethesda, MD 20892 USA. [Quenet, D.] Univ Vermont, Dept Med, Burlington, VT USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 EI 1939-4586 J9 MOL BIOL CELL JI Mol. Biol. Cell PY 2016 VL 27 MA P353 PG 1 WC Cell Biology SC Cell Biology GA EN5LM UT WOS:000396046900352 ER PT J AU Petrie, RJ Harlin, HM Yamada, KM AF Petrie, R. J. Harlin, H. M. Yamada, K. M. TI Activating the nuclear piston mechanism to generate intracellular pressure during tumor cell 3D migration. SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract CT Annual Meeting of the American-Society-for-Cell-Biology (ASCB) CY DEC 03-07, 2016 CL San Francisco, CA SP Amer Soc Cell Biol C1 [Petrie, R. J.; Harlin, H. M.] Drexel Univ, Biol, Philadelphia, PA 19104 USA. [Yamada, K. M.] Natl Inst Dent & Craniofacial Res, NIH, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 EI 1939-4586 J9 MOL BIOL CELL JI Mol. Biol. Cell PY 2016 VL 27 MA P599 PG 1 WC Cell Biology SC Cell Biology GA EN5LM UT WOS:000396046900598 ER PT J AU Pickrell, AM Sideris, DP Huang, C Wang, C Youle, RJ AF Pickrell, A. M. Sideris, D. P. Huang, C. Wang, C. Youle, R. J. TI Loss of endogenous PINK1 and Parkin affects cell growth. SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract CT Annual Meeting of the American-Society-for-Cell-Biology (ASCB) CY DEC 03-07, 2016 CL San Francisco, CA SP Amer Soc Cell Biol C1 [Pickrell, A. M.; Sideris, D. P.; Huang, C.; Wang, C.; Youle, R. J.] NINDS, NIH, Bldg 36,Rm 4D04, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 EI 1939-4586 J9 MOL BIOL CELL JI Mol. Biol. Cell PY 2016 VL 27 MA P2159 PG 1 WC Cell Biology SC Cell Biology GA EN5LO UT WOS:000396047200460 ER PT J AU Power, K Cohen-Fix, O AF Power, K. Cohen-Fix, O. TI Imbalance in phospholipid synthesis in budding yeast leads to abnormal aggregation of mitochondria. SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract CT Annual Meeting of the American-Society-for-Cell-Biology (ASCB) CY DEC 03-07, 2016 CL San Francisco, CA SP Amer Soc Cell Biol C1 [Power, K.; Cohen-Fix, O.] NIDDK, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 EI 1939-4586 J9 MOL BIOL CELL JI Mol. Biol. Cell PY 2016 VL 27 MA P2157 PG 1 WC Cell Biology SC Cell Biology GA EN5LO UT WOS:000396047200458 ER PT J AU Rahman, MM Cohen-Fix, O AF Rahman, M. M. Cohen-Fix, O. TI Metaphase chromosome alignment dictates nuclear envelope disassembly in C. elegans zygote. SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract CT Annual Meeting of the American-Society-for-Cell-Biology (ASCB) CY DEC 03-07, 2016 CL San Francisco, CA SP Amer Soc Cell Biol C1 [Rahman, M. M.; Cohen-Fix, O.] NIDDK, LCMB, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 EI 1939-4586 J9 MOL BIOL CELL JI Mol. Biol. Cell PY 2016 VL 27 MA P369 PG 2 WC Cell Biology SC Cell Biology GA EN5LM UT WOS:000396046900368 ER PT J AU Randazzo, D Khalique, U Talsness, DM Belanto, JJ Zaal, KJ Tran, MD Kenea, A Sackett, DL Ervasti, JM Ralston, E AF Randazzo, D. Khalique, U. Talsness, D. M. Belanto, J. J. Zaal, K. J. Tran, M. D. Kenea, A. Sackett, D. L. Ervasti, J. M. Ralston, E. TI Implication of tubb6, a minor beta-tubulin isotype, in muscle defects of the mdx mouse model of Duchenne muscular dystrophy. SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract CT Annual Meeting of the American-Society-for-Cell-Biology (ASCB) CY DEC 03-07, 2016 CL San Francisco, CA SP Amer Soc Cell Biol C1 [Randazzo, D.; Khalique, U.; Zaal, K. J.; Tran, M. D.; Kenea, A.; Ralston, E.] NIAMSD, Light Imaging Sect, Off Sci & Technol, NIH, Bethesda, MD 20892 USA. [Talsness, D. M.; Belanto, J. J.; Ervasti, J. M.] Univ Minnesota Twin Cities, Dept Biochem Mol Biol & Biophys, Minneapolis, MN USA. [Talsness, D. M.; Belanto, J. J.; Ervasti, J. M.] Univ Minnesota Twin Cities, Program Mol Cellular Dev Biol & Genet, Minneapolis, MN USA. [Sackett, D. L.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, NIH, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 EI 1939-4586 J9 MOL BIOL CELL JI Mol. Biol. Cell PY 2016 VL 27 MA P1798 PG 1 WC Cell Biology SC Cell Biology GA EN5LO UT WOS:000396047200099 ER PT J AU Remmert, K Beach, J Hammer, JA AF Remmert, K. Beach, J. Hammer, J. A. TI Myosin 18A localizes with myosin 2 at cell: cell junctions in epithelial cells and tissues. SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract CT Annual Meeting of the American-Society-for-Cell-Biology (ASCB) CY DEC 03-07, 2016 CL San Francisco, CA SP Amer Soc Cell Biol C1 [Remmert, K.; Beach, J.; Hammer, J. A.] NHLBI, Cell Biol & Physiol Ctr, NIH, Bldg 10, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 EI 1939-4586 J9 MOL BIOL CELL JI Mol. Biol. Cell PY 2016 VL 27 MA P955 PG 1 WC Cell Biology SC Cell Biology GA EN5LM UT WOS:000396046900954 ER PT J AU Roque, S Bui, M Pitman, M Nuccio, A Donlin-Asp, PG Nita-Lazar, A Papoian, G Dalal, Y AF Roque, S. Bui, M. Pitman, M. Nuccio, A. Donlin-Asp, P. G. Nita-Lazar, A. Papoian, G. Dalal, Y. TI Internal modifications in the CENP-A nucleosome modulate centromeric dynamics SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract CT Annual Meeting of the American-Society-for-Cell-Biology (ASCB) CY DEC 03-07, 2016 CL San Francisco, CA SP Amer Soc Cell Biol C1 [Roque, S.; Bui, M.; Dalal, Y.] NCI, CCR, Bethesda, MD 20892 USA. [Pitman, M.; Papoian, G.] Univ Maryland, UMCP, College Pk, MD 20742 USA. [Nuccio, A.; Nita-Lazar, A.] NIAID, Lab Syst Biol, 9000 Rockville Pike, Bethesda, MD 20892 USA. [Donlin-Asp, P. G.] Emory Univ, Dept Cell Biol, Atlanta, GA 30322 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 EI 1939-4586 J9 MOL BIOL CELL JI Mol. Biol. Cell PY 2016 VL 27 MA P2017 PG 2 WC Cell Biology SC Cell Biology GA EN5LO UT WOS:000396047200319 ER PT J AU Saeed, M Gil-krzewska, A Oszmiana, A Carisey, AF Mace, EM Orange, JS Krzewski, K Davis, DM AF Saeed, M. Gil-krzewska, A. Oszmiana, A. Carisey, A. F. Mace, E. M. Orange, J. S. Krzewski, K. Davis, D. M. TI Cortical Actin Remodelling for Effective Lytic Synapse Formation SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract CT Annual Meeting of the American-Society-for-Cell-Biology (ASCB) CY DEC 03-07, 2016 CL San Francisco, CA SP Amer Soc Cell Biol C1 [Saeed, M.; Oszmiana, A.; Davis, D. M.] Univ Manchester, Manchester Collaborat Ctr Inflammat Res, Manchester, Lancs, England. [Gil-krzewska, A.; Krzewski, K.] NIAID, Receptor Cell Biol Sect, Immunogenet Lab, NIH, Rockville, MD USA. [Carisey, A. F.; Mace, E. M.; Orange, J. S.] Baylor Coll Med, Ctr Human Immunobiol, Houston, TX 77030 USA. [Carisey, A. F.; Mace, E. M.; Orange, J. S.] Texas Childrens Hosp, Houston, TX 77030 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 EI 1939-4586 J9 MOL BIOL CELL JI Mol. Biol. Cell PY 2016 VL 27 MA P916 PG 1 WC Cell Biology SC Cell Biology GA EN5LM UT WOS:000396046900915 ER PT J AU Sankaralingam, P OConnell, K AF Sankaralingam, P. OConnell, K. TI Interaction and phosphorylation of SAS-5 by ZYG-1 may be important in centriole assembly SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract CT Annual Meeting of the American-Society-for-Cell-Biology (ASCB) CY DEC 03-07, 2016 CL San Francisco, CA SP Amer Soc Cell Biol C1 [Sankaralingam, P.; OConnell, K.] NIDDK, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 EI 1939-4586 J9 MOL BIOL CELL JI Mol. Biol. Cell PY 2016 VL 27 MA P205 PG 2 WC Cell Biology SC Cell Biology GA EN5LM UT WOS:000396046900205 ER PT J AU Sarraf, SA Shah, HV Wang, C Youle, RJ AF Sarraf, S. A. Shah, H. V. Wang, C. Youle, R. J. TI Loss of autophagy receptors reveals roles in the maintenance of cellular proteostasis and clearance of aggregation prone proteins SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract CT Annual Meeting of the American-Society-for-Cell-Biology (ASCB) CY DEC 03-07, 2016 CL San Francisco, CA SP Amer Soc Cell Biol C1 [Sarraf, S. A.; Shah, H. V.; Wang, C.; Youle, R. J.] NINDS, NIH, Bldg 36,Rm 4D04, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 EI 1939-4586 J9 MOL BIOL CELL JI Mol. Biol. Cell PY 2016 VL 27 MA P2315 PG 2 WC Cell Biology SC Cell Biology GA EN5LO UT WOS:000396047200615 ER PT J AU Schreiner, SM Sackett, DL Moore, JK AF Schreiner, S. M. Sackett, D. L. Moore, J. K. TI Elucidating the Role of a Human beta-tubulin, TUBB4B: Functional Analysis of a Novel Patient-Derived Mutation. SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract CT Annual Meeting of the American-Society-for-Cell-Biology (ASCB) CY DEC 03-07, 2016 CL San Francisco, CA SP Amer Soc Cell Biol C1 [Schreiner, S. M.; Moore, J. K.] Univ Colorado, Cell & Dev Biol, Anschutz Med Campus, Aurora, CO USA. [Sackett, D. L.] Eunice Kennedy Shriver NICHD, Program Phys Biol, NIH, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 EI 1939-4586 J9 MOL BIOL CELL JI Mol. Biol. Cell PY 2016 VL 27 MA P1813 PG 1 WC Cell Biology SC Cell Biology GA EN5LO UT WOS:000396047200114 ER PT J AU Shebelut, CW Rusan, NM Gavis, ER Deshpande, G Schedl, P Lerit, DA AF Shebelut, C. W. Rusan, N. M. Gavis, E. R. Deshpande, G. Schedl, P. Lerit, D. A. TI Spatial control of centrosomes is required for germline development SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract CT Annual Meeting of the American-Society-for-Cell-Biology (ASCB) CY DEC 03-07, 2016 CL San Francisco, CA SP Amer Soc Cell Biol C1 [Shebelut, C. W.] Univ Virginia, Sch Med, Charlottesville, VA 22908 USA. [Rusan, N. M.; Lerit, D. A.] NHLBI, Cell Biol & Physiol Ctr, Bldg 10, Bethesda, MD 20892 USA. [Gavis, E. R.; Deshpande, G.; Schedl, P.] Princeton Univ, Dept Mol Biol, Princeton, NJ USA. [Schedl, P.] Russian Acad Sci, Inst Gene Biol, Moscow, Russia. [Lerit, D. A.] Emory Univ, Sch Med, Dept Cell Biol, Atlanta, GA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 EI 1939-4586 J9 MOL BIOL CELL JI Mol. Biol. Cell PY 2016 VL 27 MA P213 PG 2 WC Cell Biology SC Cell Biology GA EN5LM UT WOS:000396046900213 ER PT J AU Sherry, J Elwell, C Bastidas, R Weber, M Hackstadt, T Valdivia, RH Engel, JN AF Sherry, J. Elwell, C. Bastidas, R. Weber, M. Hackstadt, T. Valdivia, R. H. Engel, J. N. TI Chlamydia trachomatis inclusion membrane protein CT192 interacts with dynactin to modulate centrosome positioning and parasitophorous vacuole fusion events. SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract CT Annual Meeting of the American-Society-for-Cell-Biology (ASCB) CY DEC 03-07, 2016 CL San Francisco, CA SP Amer Soc Cell Biol C1 [Sherry, J.; Elwell, C.; Engel, J. N.] Univ Calif San Francisco, Dept Med, San Francisco, CA USA. [Bastidas, R.; Valdivia, R. H.] Duke Univ, Dept Mol Genet & Microbiol, Durham, NC USA. [Weber, M.; Hackstadt, T.] NIAID, Host Parasite Interact Sect, Bacteriol Lab, Rocky Mt Labs,NIH, Hamilton, MT USA. [Engel, J. N.] Univ Calif San Francisco, Dept Microbiol & Immunol, San Francisco, CA 94143 USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 EI 1939-4586 J9 MOL BIOL CELL JI Mol. Biol. Cell PY 2016 VL 27 MA P2410 PG 1 WC Cell Biology SC Cell Biology GA EN5LO UT WOS:000396047200710 ER PT J AU Shorn, O Nevo-Yassaf, I Aviad, T Shepchelovich, J Perlson, E Patterson, GH Kaether, C Hirschberg, K AF Shorn, O. Nevo-Yassaf, I. Aviad, T. Shepchelovich, J. Perlson, E. Patterson, G. H. Kaether, C. Hirschberg, K. TI COPII sorts cargo into spatially distinct ER domains prior to fission of Golgi-bound transport carriers. SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract CT Annual Meeting of the American-Society-for-Cell-Biology (ASCB) CY DEC 03-07, 2016 CL San Francisco, CA SP Amer Soc Cell Biol C1 [Shorn, O.; Nevo-Yassaf, I.; Aviad, T.; Shepchelovich, J.; Hirschberg, K.] Tel Aviv Univ, Sackler Sch Med, Pathol, Tel Aviv, Israel. [Perlson, E.] Tel Aviv Univ, Sackler Sch Med, Physiol & Pharmacol, Tel Aviv, Israel. [Patterson, G. H.] NIBIB, Sect Biophoton, NIH, Rockville, MD USA. [Kaether, C.] Fritz Lipmann Inst, Leibniz Inst Age Res, Jena, Germany. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 EI 1939-4586 J9 MOL BIOL CELL JI Mol. Biol. Cell PY 2016 VL 27 MA P415 PG 1 WC Cell Biology SC Cell Biology GA EN5LM UT WOS:000396046900414 ER PT J AU Shu, S Liu, X Billington, N Williamson, CD Yu, S Brezska, HB Donaldson, J Sellers, JR Korn, ED AF Shu, S. Liu, X. Billington, N. Williamson, C. D. Yu, S. Brezska, H. B. Donaldson, J. Sellers, J. R. Korn, E. D. TI Mammalian nonmuscle myosin II binds to anionic phospholipids with concomitant dissociation of the regulatory light chain. SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract CT Annual Meeting of the American-Society-for-Cell-Biology (ASCB) CY DEC 03-07, 2016 CL San Francisco, CA SP Amer Soc Cell Biol C1 [Shu, S.; Liu, X.; Billington, N.; Williamson, C. D.; Yu, S.; Brezska, H. B.; Donaldson, J.; Sellers, J. R.; Korn, E. D.] NHLBI, NIH, Bldg 10, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 EI 1939-4586 J9 MOL BIOL CELL JI Mol. Biol. Cell PY 2016 VL 27 MA P965 PG 2 WC Cell Biology SC Cell Biology GA EN5LM UT WOS:000396046900964 ER PT J AU Sideris, DP Pickrell, AM Giagtzoglou, N Wang, C Youle, RJ AF Sideris, D. P. Pickrell, A. M. Giagtzoglou, N. Wang, C. Youle, R. J. TI Mitochondrial damage affects cell growth and cell cycle progression by PINK1/Parkin SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract CT Annual Meeting of the American-Society-for-Cell-Biology (ASCB) CY DEC 03-07, 2016 CL San Francisco, CA SP Amer Soc Cell Biol C1 [Sideris, D. P.; Pickrell, A. M.; Wang, C.; Youle, R. J.] NINDS, NIH, Bldg 36,Rm 4D04, Bethesda, MD 20892 USA. [Giagtzoglou, N.] Biogen Inc, Pathway Discovery, 14 Cambridge Ctr, Cambridge, MA 02142 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 EI 1939-4586 J9 MOL BIOL CELL JI Mol. Biol. Cell PY 2016 VL 27 MA P531 PG 2 WC Cell Biology SC Cell Biology GA EN5LM UT WOS:000396046900530 ER PT J AU Skau, CT Fischer, RS Gurel, PS Thiam, HR Tubbs, A Baird, MA Davidson, MW Piel, M Alushin, GM Nussenzweig, A Steeg, PS Waterman, CM AF Skau, C. T. Fischer, R. S. Gurel, P. S. Thiam, H. R. Tubbs, A. Baird, M. A. Davidson, M. W. Piel, M. Alushin, G. M. Nussenzweig, A. Steeg, P. S. Waterman, C. M. TI FMN2 is a melanoma metastasis- promoter that mediates formation of a perinuclear actin/adhesion system to protect nuclei and DNA from damage during confined cell migration SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract CT Annual Meeting of the American-Society-for-Cell-Biology (ASCB) CY DEC 03-07, 2016 CL San Francisco, CA SP Amer Soc Cell Biol C1 [Skau, C. T.; Fischer, R. S.; Gurel, P. S.; Thiam, H. R.; Baird, M. A.; Alushin, G. M.; Waterman, C. M.] NHLBI, Cell Biol & Physiol Ctr, NIH, Bldg 10, Bethesda, MD 20892 USA. [Thiam, H. R.; Piel, M.] Inst Curie, CNRS, UMR 144, Paris, France. [Tubbs, A.; Nussenzweig, A.] NCI, Lab Genome Integr, NIH, Bethesda, MD 20892 USA. [Baird, M. A.; Davidson, M. W.] Florida State Univ, Magnet Lab, Tallahassee, FL 32306 USA. [Steeg, P. S.] NCI, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 EI 1939-4586 J9 MOL BIOL CELL JI Mol. Biol. Cell PY 2016 VL 27 MA P917 PG 1 WC Cell Biology SC Cell Biology GA EN5LM UT WOS:000396046900916 ER PT J AU Stepicheva, NA Dumas, M Kobi, P Donaldson, JG Song, JL AF Stepicheva, N. A. Dumas, M. Kobi, P. Donaldson, J. G. Song, J. L. TI The small GTPase Arf6 regulates sea urchin morphogenesis. SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract CT Annual Meeting of the American-Society-for-Cell-Biology (ASCB) CY DEC 03-07, 2016 CL San Francisco, CA SP Amer Soc Cell Biol C1 [Stepicheva, N. A.; Dumas, M.; Kobi, P.; Song, J. L.] Univ Delaware, Biol Sci, Newark, DE USA. [Donaldson, J. G.] NHLBI, Cell Biol & Physiol Ctr, NIH, Bldg 10, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 EI 1939-4586 J9 MOL BIOL CELL JI Mol. Biol. Cell PY 2016 VL 27 MA P773 PG 1 WC Cell Biology SC Cell Biology GA EN5LM UT WOS:000396046900772 ER PT J AU Sun, X Park, JH Roll-Mecak, A Li, T AF Sun, X. Park, J. H. Roll-Mecak, A. Li, T. TI Loss of RPGR glutamylation underlies the pathogenic mechanism of retinal dystrophy caused by TTLL5 mutations. SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract CT Annual Meeting of the American-Society-for-Cell-Biology (ASCB) CY DEC 03-07, 2016 CL San Francisco, CA SP Amer Soc Cell Biol C1 [Sun, X.; Li, T.] NEI, NIH, Bethesda, MD 20892 USA. [Park, J. H.; Roll-Mecak, A.] NINDS, NIH, Bldg 36,Rm 4D04, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 EI 1939-4586 J9 MOL BIOL CELL JI Mol. Biol. Cell PY 2016 VL 27 MA P1786 PG 1 WC Cell Biology SC Cell Biology GA EN5LO UT WOS:000396047200087 ER PT J AU Swaminathan, V Mathew, JK Mehta, S Nordenfelt, P Moore, TI Nobuyasu, K Baker, D Oldenbourg, R Tani, T Mayor, S Springer, TA Waterman, CM AF Swaminathan, V. Mathew, J. K. Mehta, S. Nordenfelt, P. Moore, T. I. Nobuyasu, K. Baker, D. Oldenbourg, R. Tani, T. Mayor, S. Springer, T. A. Waterman, C. M. TI Actin retrograde flow actively aligns and orients ligand-engaged integrins in focal adhesions. SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract CT Annual Meeting of the American-Society-for-Cell-Biology (ASCB) CY DEC 03-07, 2016 CL San Francisco, CA SP Amer Soc Cell Biol C1 [Swaminathan, V.; Waterman, C. M.] NHLBI, Cell Biol & Physiol Ctr, NIH, Bldg 10, Bethesda, MD 20892 USA. [Mathew, J. K.; Mayor, S.] Natl Ctr Biol Sci, Bangalore, Karnataka, India. [Mehta, S.; Oldenbourg, R.; Tani, T.] Marine Biol Sci, Woods Hole, MA USA. [Nordenfelt, P.] Lund Univ, Div Infect Med, Lund, MD, Sweden. [Moore, T. I.; Springer, T. A.] Harvard Univ, Program Cellular & Mol Med, Boston, MA 02115 USA. [Nobuyasu, K.; Baker, D.] Univ Washington, Dept Biochem, Seattle, WA 98195 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 EI 1939-4586 J9 MOL BIOL CELL JI Mol. Biol. Cell PY 2016 VL 27 MA P646 PG 2 WC Cell Biology SC Cell Biology GA EN5LM UT WOS:000396046900645 ER PT J AU Thiam, HR Waterman, CM AF Thiam, H. R. Waterman, C. M. TI Spatiotemporal regulation of focal adhesions disassembly at the G2/M transition of the cell cycle. SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract CT Annual Meeting of the American-Society-for-Cell-Biology (ASCB) CY DEC 03-07, 2016 CL San Francisco, CA SP Amer Soc Cell Biol C1 [Thiam, H. R.; Waterman, C. M.] NHLBI, NIH, Bldg 10, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 EI 1939-4586 J9 MOL BIOL CELL JI Mol. Biol. Cell PY 2016 VL 27 MA P666 PG 2 WC Cell Biology SC Cell Biology GA EN5LM UT WOS:000396046900665 ER PT J AU Thiam, HR Wong, SL Wagner, DD Waterman, CM AF Thiam, H. R. Wong, S. L. Wagner, D. D. Waterman, C. M. TI Cellular events mediating extracellular trap formation in neutrophil-like granulocytes. SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract CT Annual Meeting of the American-Society-for-Cell-Biology (ASCB) CY DEC 03-07, 2016 CL San Francisco, CA SP Amer Soc Cell Biol C1 [Thiam, H. R.; Waterman, C. M.] NHLBI, NIH, Bldg 10, Bethesda, MD 20892 USA. [Wong, S. L.; Wagner, D. D.] Boston Childrens Hosp, Program Cellular & Mol Med, Boston, MA USA. [Wong, S. L.; Wagner, D. D.] Harvard Med Sch, Dept Pediat, Boston, MA USA. [Wagner, D. D.] Boston Childrens Hosp, Div Hematol Oncol, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 EI 1939-4586 J9 MOL BIOL CELL JI Mol. Biol. Cell PY 2016 VL 27 MA P1746 PG 2 WC Cell Biology SC Cell Biology GA EN5LO UT WOS:000396047200047 ER PT J AU Toulmay, A Murley, A Sarsam, R Yamada, J Nunnari, J Prinz, W AF Toulmay, A. Murley, A. Sarsam, R. Yamada, J. Nunnari, J. Prinz, W. TI Role of membrane contact sites in formation of lipid domains during stress SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract CT Annual Meeting of the American-Society-for-Cell-Biology (ASCB) CY DEC 03-07, 2016 CL San Francisco, CA SP Amer Soc Cell Biol C1 [Toulmay, A.; Prinz, W.] NIDDK, LCMB, NIH, Bethesda, MD 20892 USA. [Murley, A.; Sarsam, R.; Yamada, J.; Nunnari, J.] Univ Calif Davis, Dept Mol & Cellular Biol, Davis, CA 95616 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 EI 1939-4586 J9 MOL BIOL CELL JI Mol. Biol. Cell PY 2016 VL 27 MA P550 PG 1 WC Cell Biology SC Cell Biology GA EN5LM UT WOS:000396046900549 ER PT J AU Valm, AM Cohen, S Legant, WR Melunis, J Hershberg, U Wait, E Cohen, AR Davidson, MW Betzig, E Lippincott-Schwartz, J AF Valm, A. M. Cohen, S. Legant, W. R. Melunis, J. Hershberg, U. Wait, E. Cohen, A. R. Davidson, M. W. Betzig, E. Lippincott-Schwartz, J. TI Spectral imaging and computational analysis reveals the systems level organelle interactome. SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract CT Annual Meeting of the American-Society-for-Cell-Biology (ASCB) CY DEC 03-07, 2016 CL San Francisco, CA SP Amer Soc Cell Biol C1 [Valm, A. M.; Cohen, S.; Lippincott-Schwartz, J.] NICHD, NIH, Bethesda, MD USA. [Legant, W. R.; Betzig, E.; Lippincott-Schwartz, J.] HHMI, Janelia Res Campus, Ashburn, VA USA. [Melunis, J.; Hershberg, U.] Drexel Univ, Sch Biomed Engn Sci & Hlth Syst, Philadelphia, PA 19104 USA. [Hershberg, U.] Drexel Univ, Coll Med, Dept Microbiol & Immunol, Philadelphia, PA 19104 USA. [Wait, E.; Cohen, A. R.] Drexel Univ, Coll Engn, Dept Elect & Comp Engn, Philadelphia, PA 19104 USA. [Davidson, M. W.] Florida State Univ, Natl High Magnet Feild Lab, Tallahassee, FL 32306 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 EI 1939-4586 J9 MOL BIOL CELL JI Mol. Biol. Cell PY 2016 VL 27 MA P48 PG 1 WC Cell Biology SC Cell Biology GA EN5LM UT WOS:000396046900049 ER PT J AU Vecchiarelli, AG Mizuuchi, K AF Vecchiarelli, A. G. Mizuuchi, K. TI Mechanistic insights of the Min Oscillator via cell-free reconstitution and imaging. SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract CT Annual Meeting of the American-Society-for-Cell-Biology (ASCB) CY DEC 03-07, 2016 CL San Francisco, CA SP Amer Soc Cell Biol C1 [Vecchiarelli, A. G.; Mizuuchi, K.] NIH, Bldg 10, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 EI 1939-4586 J9 MOL BIOL CELL JI Mol. Biol. Cell PY 2016 VL 27 MA P797 PG 1 WC Cell Biology SC Cell Biology GA EN5LM UT WOS:000396046900796 ER PT J AU Walia, V Vetter, M Insinna, C Lu, Q Ritt, D Specht, S Stauffer, J Morrison, D Lorentzen, E Westlake, CJ AF Walia, V. Vetter, M. Insinna, C. Lu, Q. Ritt, D. Specht, S. Stauffer, J. Morrison, D. Lorentzen, E. Westlake, C. J. TI Growth factor signaling regulation of a Rab-effector switch required for ciliogenesis initiation SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract CT Annual Meeting of the American-Society-for-Cell-Biology (ASCB) CY DEC 03-07, 2016 CL San Francisco, CA SP Amer Soc Cell Biol C1 [Walia, V.; Insinna, C.; Lu, Q.; Ritt, D.; Specht, S.; Stauffer, J.; Morrison, D.; Westlake, C. J.] NCI, Ctr Canc Res, Frederick, MD 21701 USA. [Vetter, M.; Lorentzen, E.] Max Plank Inst Biochem, Martinsried, Germany. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 EI 1939-4586 J9 MOL BIOL CELL JI Mol. Biol. Cell PY 2016 VL 27 MA P1827 PG 1 WC Cell Biology SC Cell Biology GA EN5LO UT WOS:000396047200129 ER PT J AU Walters, AD Wang, R Gadal, O Cohen-Fix, O AF Walters, A. D. Wang, R. Gadal, O. Cohen-Fix, O. TI Mutations in the Sec pathway lead to altered nuclear morphology in Saccharomyces cerevisiae. SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract CT Annual Meeting of the American-Society-for-Cell-Biology (ASCB) CY DEC 03-07, 2016 CL San Francisco, CA SP Amer Soc Cell Biol C1 [Walters, A. D.; Cohen-Fix, O.] NIDDK, NIH, Bethesda, MD 20892 USA. [Wang, R.; Gadal, O.] Toulouse Univ, Toulouse, France. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 EI 1939-4586 J9 MOL BIOL CELL JI Mol. Biol. Cell PY 2016 VL 27 MA P2146 PG 1 WC Cell Biology SC Cell Biology GA EN5LO UT WOS:000396047200447 ER PT J AU Wang, C Nezich, C Youle, RJ Zhen, C AF Wang, C. Nezich, C. Youle, R. J. Zhen, C. TI Autophagy machinery genes are differentially required for autophagy and Parkin-mediated mitophagy SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract CT Annual Meeting of the American-Society-for-Cell-Biology (ASCB) CY DEC 03-07, 2016 CL San Francisco, CA SP Amer Soc Cell Biol C1 [Wang, C.; Nezich, C.; Youle, R. J.] NINDS, SNB, NIH, Bldg 36,Rm 4D04, Bethesda, MD 20892 USA. [Zhen, C.] CALTECH, Dept Biochem, Pasadena, CA 91125 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 EI 1939-4586 J9 MOL BIOL CELL JI Mol. Biol. Cell PY 2016 VL 27 MA P2331 PG 1 WC Cell Biology SC Cell Biology GA EN5LO UT WOS:000396047200631 ER PT J AU Wu, C Feng, X Udey, MC AF Wu, C. Feng, X. Udey, M. C. TI EpCAM cleavage by matriptase regulates intestinal epithelial function. SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract CT Annual Meeting of the American-Society-for-Cell-Biology (ASCB) CY DEC 03-07, 2016 CL San Francisco, CA SP Amer Soc Cell Biol C1 [Wu, C.; Feng, X.; Udey, M. C.] NCI, Dermatol Branch, Bldg 10, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 EI 1939-4586 J9 MOL BIOL CELL JI Mol. Biol. Cell PY 2016 VL 27 MA P639 PG 1 WC Cell Biology SC Cell Biology GA EN5LM UT WOS:000396046900638 ER PT J AU Wu, Z Plotnikov, SV Moalim, AY Waterman, CM Liu, J AF Wu, Z. Plotnikov, S. V. Moalim, A. Y. Waterman, C. M. Liu, J. TI Two distinct actin networks mediate traction oscillations to confer mechanosensitivity of focal adhesions. SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract CT Annual Meeting of the American-Society-for-Cell-Biology (ASCB) CY DEC 03-07, 2016 CL San Francisco, CA SP Amer Soc Cell Biol C1 [Wu, Z.; Waterman, C. M.; Liu, J.] NHLBI, NIH, Bldg 10, Bethesda, MD 20892 USA. [Plotnikov, S. V.; Moalim, A. Y.] Univ Toronto, Dept Cell Syst Biol, Toronto, ON, Canada. NR 0 TC 0 Z9 0 U1 1 U2 1 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 EI 1939-4586 J9 MOL BIOL CELL JI Mol. Biol. Cell PY 2016 VL 27 MA P2242 PG 1 WC Cell Biology SC Cell Biology GA EN5LO UT WOS:000396047200542 ER PT J AU Yan, Y Yu, L Castro, L Dixon, D AF Yan, Y. Yu, L. Castro, L. Dixon, D. TI Estrogen receptor alpha 36 is mostly localized in mitochondria in human uterine smooth muscle and leiomyoma cells SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract CT Annual Meeting of the American-Society-for-Cell-Biology (ASCB) CY DEC 03-07, 2016 CL San Francisco, CA SP Amer Soc Cell Biol C1 [Yan, Y.; Yu, L.; Castro, L.; Dixon, D.] NIEHS, Mol Pathogenesis Grp, NTPL, DNTP,NIH,DHHS, POB 12233, Res Triangle Pk, NC 27709 USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 EI 1939-4586 J9 MOL BIOL CELL JI Mol. Biol. Cell PY 2016 VL 27 MA P528 PG 2 WC Cell Biology SC Cell Biology GA EN5LM UT WOS:000396046900527 ER PT J AU Yim, Y Laakso, J Alexander, C Mustapha, M Cheney, R Hammer, J AF Yim, Y. Laakso, J. Alexander, C. Mustapha, M. Cheney, R. Hammer, J. TI Myosin 10 function in cerebellar Purkinje neurons. SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract CT Annual Meeting of the American-Society-for-Cell-Biology (ASCB) CY DEC 03-07, 2016 CL San Francisco, CA SP Amer Soc Cell Biol C1 [Yim, Y.; Alexander, C.; Hammer, J.] NIH, Lab Cell Biol, Bldg 10, Bethesda, MD 20892 USA. [Laakso, J.] Endocrine Soc, Sci Policy, Washington Dc, DC USA. [Mustapha, M.] Stanford Univ, Sch Med, Palo Alto, CA 94304 USA. [Cheney, R.] Univ North Carolina Chapel Hill, Sch Med, Chapel Hill, NC USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 EI 1939-4586 J9 MOL BIOL CELL JI Mol. Biol. Cell PY 2016 VL 27 MA P959 PG 2 WC Cell Biology SC Cell Biology GA EN5LM UT WOS:000396046900958 ER PT J AU Wang, S Lin, J Wang, TF Chen, XY Huang, P AF Wang, Sheng Lin, Jing Wang, Tianfu Chen, Xiaoyuan Huang, Peng TI Recent Advances in Photoacoustic Imaging for Deep-Tissue Biomedical Applications SO THERANOSTICS LA English DT Review DE Photoacoustic imaging ID GUIDED PHOTOTHERMAL THERAPY; REDUCED GRAPHENE OXIDE; SEMICONDUCTING POLYMER NANOPARTICLES; INFRARED FLUORESCENT-PROBE; ENHANCED RAMAN-SCATTERING; GOLD NANOROD VESICLES; AG2S QUANTUM-DOT; IN-VIVO; PHOTODYNAMIC THERAPY; CANCER-THERAPY AB Photoacoustic imaging (PAI), a novel imaging modality based on photoacoustic effect, shows great promise in biomedical applications. By converting pulsed laser excitation into ultrasonic emission, PAI combines the advantages of optical imaging and ultrasound imaging, which benefits rich contrast, high resolution and deep tissue penetration. In this paper, we introduced recent advances of contrast agents, applications, and signal enhancement strategies for PAI. The PA contrast agents were categorized by their components, mainly including inorganic and organic PA contrast agents. The applications of PAI were summarized as follows: deep tumor imaging, therapeutic responses monitoring, metabolic imaging, pH detection, enzyme detection, reactive oxygen species (ROS) detection, metal ions detection, and so on. The enhancement strategies of PA signals were highlighted. In the end, we elaborated on the challenges and provided perspectives of PAI for deep-tissue biomedical applications. C1 [Wang, Sheng; Lin, Jing; Wang, Tianfu; Huang, Peng] Shenzhen Univ, Dept Biomed Engn, Sch Med, Guangdong Key Lab Biomed Measurements & Ultrasoun, Shenzhen 518060, Peoples R China. [Wang, Sheng] Shenzhen Univ, Coll Optoelect Engn, Key Lab Optoelect Devices & Syst, Minist Educ & Guangdong Prov, Shenzhen 518060, Peoples R China. [Wang, Sheng; Chen, Xiaoyuan] Natl Inst Biomed Imaging & Bioengn, Lab Mol Imaging & Nanomed, NIH, Bethesda, MD 20892 USA. RP Huang, P (reprint author), Shenzhen Univ, Dept Biomed Engn, Sch Med, Guangdong Key Lab Biomed Measurements & Ultrasoun, Shenzhen 518060, Peoples R China.; Chen, XY (reprint author), Natl Inst Biomed Imaging & Bioengn, Lab Mol Imaging & Nanomed, NIH, Bethesda, MD 20892 USA. EM shawn.chen@nih.gov; peng.huang@szu.edu.cn FU National Science Foundation of China [81401465, 51573096]; Intramural Research Program (IRP) of the NIBIB, NIH FX This work was supported by the National Science Foundation of China (81401465, 51573096), and the Intramural Research Program (IRP) of the NIBIB, NIH. NR 150 TC 2 Z9 2 U1 4 U2 4 PU IVYSPRING INT PUBL PI LAKE HAVEN PA PO BOX 4546, LAKE HAVEN, NSW 2263, AUSTRALIA SN 1838-7640 J9 THERANOSTICS JI Theranostics PY 2016 VL 6 IS 13 BP 2394 EP 2413 DI 10.7150/thno.16715 PG 20 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA EO2UN UT WOS:000396551600010 PM 27877243 ER PT J AU Xu, MD Zhou, BHP Tao, M Liu, JY Li, W AF Xu, Mengdan Zhou, Binhua P. Tao, Min Liu, Jingyi Li, Wei TI The Role of Stromal Components in Pancreatic Cancer Progression SO ANTI-CANCER AGENTS IN MEDICINAL CHEMISTRY LA English DT Review DE Pancreatic cancer; pancreatic stellate cells; fibroblasts; mast cells; macrophages; neural components; dendritic cells ID TUMOR-ASSOCIATED MACROPHAGES; EPITHELIAL-MESENCHYMAL TRANSITION; STELLATE CELLS; DUCTAL ADENOCARCINOMA; DENDRITIC CELLS; MAST-CELLS; CARCINOMA-CELLS; IN-VITRO; NEURONAL PLASTICITY; NEURAL INVASION AB Pancreatic ductal adenocarcinoma (PDAC) is one of the most lethal human cancers, and is known for its extremely poor prognosis. Because of the location and composition of the organ, early symptoms cannot be visualized as easily as in other solid tumors. In the past decades, researchers have been mostly working on the genetic and epigenetic alterations of the cancer cells themselves, and therapies on pancreatic cancer cells alone have failed to significantly improve patient outcome. With the identification of abundant tumor stromal responses, the focus of pancreatic cancer research has begun to change. Increasing evidence has proved that the tumor stroma, especially the cell components (such as pancreatic stellate cells, tumor-associated macrophages, mast cells etc.) plays a key role in the development of PDAC. In this review, we discuss the interactions between cancer cells and several important cell components of the tumor stroma, as well their role in tumor growth, migration, invasion, angiogenesis and immune recognition. C1 [Xu, Mengdan; Tao, Min; Li, Wei] Soochow Univ, Affiliated Hosp 1, Dept Oncol, Suzhou 215006, Peoples R China. [Zhou, Binhua P.; Li, Wei] Univ Kentucky, Coll Med, Markey Canc Ctr, Lexington, KY 40506 USA. [Zhou, Binhua P.] Univ Kentucky, Coll Med, Dept Mol, Lexington, KY 40506 USA. [Zhou, Binhua P.] Univ Kentucky, Coll Med, Dept Cellular Biochem, Lexington, KY 40506 USA. [Liu, Jingyi] NCI, Frederick, MD 21702 USA. RP Li, W (reprint author), Soochow Univ, Affiliated Hosp 1, Dept Oncol, Suzhou 215006, Peoples R China.; Liu, JY (reprint author), NCI, Frederick, MD 21702 USA. EM jingyi.liu@nih.gov; liwei10@suda.edu.cn FU National Natural Science Foundation of China [81472296, 81101867, 81272542, 81200369, 81502275, 81572992]; China International Medical Foundation [CIMF-F-H001-057]; Six Major Talent Peak Project of Jiangsu Province [2015-WSN-022]; Special Foundation of Clinical Medicine of Jiangsu Provincial Bureau of Science and Technology [BL2014039]; Scientific Research Project of Jiangsu Provincial Bureau of Traditional Chinese Medicine [L213236]; Medical Scientific Research Project of Jiangsu Provincial Bureau of Health [Z201206]; Special Foundation of Wu Jieping Medical Foundation for Clinical Scientific Research [320.6753.1225, 320.6750.12242]; Science and Education for Health Foundation of Suzhou for Youth [SWKQ1003, SWKQ1011]; Science and Technology Project Foundation of Suzhou [SYS201112, SYSD2012137, SYS201335]; Soochow University [P112200315, P112200914] FX This study was supported by the National Natural Science Foundation of China (grant nos. 81472296, 81101867, 81272542, 81200369, 81502275, and 81572992), the China International Medical Foundation (grant no. CIMF-F-H001-057), the Six Major Talent Peak Project of Jiangsu Province (grant no. 2015-WSN-022), the Special Foundation of Clinical Medicine of Jiangsu Provincial Bureau of Science and Technology (grant no. BL2014039), the Scientific Research Project of Jiangsu Provincial Bureau of Traditional Chinese Medicine (grant no. L213236), the Medical Scientific Research Project of Jiangsu Provincial Bureau of Health (grant no. Z201206), the Special Foundation of Wu Jieping Medical Foundation for Clinical Scientific Research (grant nos. 320.6753.1225 and 320.6750.12242), the Science and Education for Health Foundation of Suzhou for Youth (grant nos. SWKQ1003 and SWKQ1011), the Science and Technology Project Foundation of Suzhou (grant nos. SYS201112, SYSD2012137 and SYS201335) and transverse project of Soochow University (grant nos. P112200315 and P112200914). NR 110 TC 1 Z9 1 U1 1 U2 1 PU BENTHAM SCIENCE PUBL LTD PI SHARJAH PA EXECUTIVE STE Y-2, PO BOX 7917, SAIF ZONE, 1200 BR SHARJAH, U ARAB EMIRATES SN 1871-5206 EI 1875-5992 J9 ANTI-CANCER AGENT ME JI Anti-Cancer Agents Med. Chem. PY 2016 VL 16 IS 9 BP 1117 EP 1124 DI 10.2174/1871520616666160404115532 PG 8 WC Oncology; Chemistry, Medicinal SC Oncology; Pharmacology & Pharmacy GA DU5QM UT WOS:000382266400007 PM 27039918 ER PT J AU Zhu, BZ Saleh, J Isgrig, KT Cunningham, LL Chien, WW AF Zhu, Bovey Z. Saleh, Jasmine Isgrig, Kevin T. Cunningham, Lisa L. Chien, Wade W. TI Hearing Loss after Round Window Surgery in Mice Is due to Middle Ear Effusion SO AUDIOLOGY AND NEURO-OTOLOGY LA English DT Article DE Ear surgery; Hearing loss; Inner ear; Middle ear; Round window membrane; Gene therapy ID COCHLEAR GENE-TRANSFER; OTITIS-MEDIA; MOUSE MODEL; THERAPY; INOCULATION; ADENOVIRUS; VECTOR AB Background: Delivery of therapeutic agents directly through the round window (RW) offers promise for treating sensorineural hearing loss. However, hearing loss can result from the surgical approach itself, and the reasons for this are poorly understood. We examined the hearing loss following the 3 major steps involved with the RW approach to access the mouse cochlea: bullostomy, RW puncture, and RW injection. Methods: Twenty-one adult CBA/J mice underwent bullostomy alone, 10 underwent RW puncture, and 8 underwent RW injection with PBS with 5% glycerol. Auditory brainstem responses (ABR) and otoscopy were performed preoperatively and up to 6 weeks postoperatively. Hair cells were stained, and survival was assessed using immunofluorescence. Results: One week postoperatively, mice in all groups showed significant threshold shifts. Otoscopy revealed approximately half of all mice had middle ear effusion (MEE), with a higher incidence of effusion in the RW puncture and RW injection groups. Those with MEE had significant ABR threshold shifts, whereas those without MEE had minimal hearing loss. MEE persisted through 6 weeks in a majority of cases, but in those mice with MEE resolution, there was at least partial improvement in hearing. Immunohistochemistry showed minimal loss of hair cells in all animals. Conclusion: MEE is highly correlated with hearing loss in mice undergoing RW surgery. Otoscopy is an important adjunct to consider after ear surgery in mice, as MEE may contribute to postsurgical hearing loss. (C) 2017 S. Karger AG, Basel C1 [Zhu, Bovey Z.; Saleh, Jasmine; Isgrig, Kevin T.; Chien, Wade W.] Natl Inst Deafness & Other Commun Disorders, Neurotol Program, NIH, Bethesda, MD USA. [Saleh, Jasmine; Cunningham, Lisa L.] Natl Inst Deafness & Other Commun Disorders, Sect Sensory Cell Biol, NIH, Bethesda, MD USA. [Zhu, Bovey Z.] Walter Reed Natl Mil Med Ctr, Dept Otolaryngol Head & Neck Surg, Bethesda, MD USA. [Chien, Wade W.] Johns Hopkins Sch Med, Dept Otolaryngol Head & Neck Surg, Baltimore, MD USA. RP Chien, WW (reprint author), 35 Convent Dr,Bldg 35A,Suite 1F-220, Bethesda, MD 20892 USA. EM wade.chien@nih.gov FU National Institutes of Health/ National Institute on Deafness and Other Communication Disorders, Division of Intramural Research [DC00082-02, DC00079-04] FX We thank Dr. Carmen Brewer and Dr. Carter Van Waes for their comments on the manuscript. We thank the NIDCD animal facility for providing care to the mice that underwent ear surgeries. We thank Dr. Tracy Fitzgerald for providing help with auditory testing. This work was supported by National Institutes of Health/ National Institute on Deafness and Other Communication Disorders, Division of Intramural Research DC00082-02 (to W.W.C.) and DC00079-04 (to L.L.C). NR 22 TC 0 Z9 0 U1 0 U2 0 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 1420-3030 EI 1421-9700 J9 AUDIOL NEURO-OTOL JI Audiol. Neuro-Otol. PY 2016 VL 21 IS 6 BP 356 EP 364 DI 10.1159/000449239 PG 9 WC Audiology & Speech-Language Pathology; Neurosciences; Otorhinolaryngology SC Audiology & Speech-Language Pathology; Neurosciences & Neurology; Otorhinolaryngology GA EL5WB UT WOS:000394691000002 ER PT S AU de Herrera, AGS Schaer, R Antani, S Muller, H AF Seco de Herrera, Alba Garcia Schaer, Roger Antani, Sameer Mueller, Henning BE Carneiro, G Mateus, D Peter, L Bradley, A Tavares, JMRS Belagiannis, V Papa, JP Nascimento, JC Loog, M Lu, Z Cardoso, JS Cornebise, J TI Using Crowdsourcing for Multi-label Biomedical Compound Figure Annotation SO DEEP LEARNING AND DATA LABELING FOR MEDICAL APPLICATIONS SE Lecture Notes in Computer Science LA English DT Proceedings Paper CT 2nd International Workshop on Deep Learning in Medical Image Analysis (DLMIA) / 1st International Workshop on Large-Scale Annotation of Biomedical Data and Expert Label Synthesis (LABELS) CY OCT 21, 2016 CL Athens, GREECE DE Multi-label annotation; Compound figures; Crowdsourcing AB Information analysis or retrieval for images in the biomedical literature needs to deal with a large amount of compound figures (figures containing several subfigures), as they constitute probably more than half of all images in repositories such as PubMed Central, which was the data set used for the task. The ImageCLEFmed benchmark proposed among other tasks in 2015 and 2016 a multi-label classification task, which aims at evaluating the automatic classification of figures into 30 image types. This task was based on compound figures and thus the figures were distributed to participants as compound figures but also in a separated form. Therefore, the generation of a gold standard was required, so that algorithms of participants can be evaluated and compared. This work presents the process carried out to generate the multi-labels of similar to 2650 compound figures using a crowdsourcing approach. Automatic algorithms to separate compound figures into subfigures were used and the results were then validated or corrected via crowdsourcing. The image types (MR, CT, X-ray,...) were also annotated by crowdsourcing including detailed quality control. Quality control is necessary to insure quality of the annotated data as much as possible. similar to 625 h were invested with a cost of similar to 870$. C1 [Seco de Herrera, Alba Garcia; Antani, Sameer] Natl Lib Med, Lister Hill Natl Ctr Biomed Commun, Bethesda, MD USA. [Schaer, Roger; Mueller, Henning] Univ Appl Sci Western Switzerland HES SO, Sierre, Switzerland. RP de Herrera, AGS (reprint author), Natl Lib Med, Lister Hill Natl Ctr Biomed Commun, Bethesda, MD USA. EM albagarcia@nih.gov NR 17 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER INT PUBLISHING AG PI CHAM PA GEWERBESTRASSE 11, CHAM, CH-6330, SWITZERLAND SN 0302-9743 BN 978-3-319-46976-8; 978-3-319-46975-1 J9 LECT NOTES COMPUT SC PY 2016 VL 10008 BP 228 EP 237 DI 10.1007/978-3-319-46976-8_24 PG 10 WC Computer Science, Information Systems; Computer Science, Interdisciplinary Applications; Medical Informatics; Radiology, Nuclear Medicine & Medical Imaging SC Computer Science; Medical Informatics; Radiology, Nuclear Medicine & Medical Imaging GA BG6CD UT WOS:000389936900024 ER PT S AU Gao, MC Xu, ZY Lu, L Harrison, AP Summers, RM Mollura, DJ AF Gao, Mingchen Xu, Ziyue Lu, Le Harrison, Adam P. Summers, Ronald M. Mollura, Daniel J. BE Wang, L Adeli, E Wang, Q Shi, Y Suk, HI TI Multi-label Deep Regression and Unordered Pooling for Holistic Interstitial Lung Disease Pattern Detection SO MACHINE LEARNING IN MEDICAL IMAGING, MLMI 2016 SE Lecture Notes in Computer Science LA English DT Proceedings Paper CT 7th International Workshop on Machine Learning in Medical Imaging (MLMI) CY OCT 17, 2016 CL Athens, GREECE DE Interstitial lung disease detection; Convolutional neural network; Multi-label deep regression; Unordered pooling; Fisher vector encoding ID CLASSIFICATION AB Holistically detecting interstitial lung disease (ILD) patterns from CT images is challenging yet clinically important. Unfortunately, most existing solutions rely on manually provided regions of interest, limiting their clinical usefulness. In addition, no work has yet focused on predicting more than one ILD from the same CT slice, despite the frequency of such occurrences. To address these limitations, we propose two variations of multi-label deep convolutional neural networks (CNNs). The first uses a deep CNN to detect the presence of multiple ILDs using a regression-based loss function. Our second variant further improves performance, using spatially invariant Fisher Vector encoding of the CNN feature activations. We test our algorithms on a dataset of 533 patients using five-fold cross-validation, achieving high area-under-curve (AUC) scores of 0.982, 0.972, 0.893 and 0.993 for Ground Glass, Reticular, Honeycomb and Emphysema, respectively. As such, our work represents an important step forward in providing clinically effective ILD detection. C1 [Gao, Mingchen; Xu, Ziyue; Lu, Le; Harrison, Adam P.; Summers, Ronald M.; Mollura, Daniel J.] NIH, Dept Radiol & Imaging Sci, Bldg 10, Bethesda, MD 20892 USA. RP Gao, MC (reprint author), NIH, Dept Radiol & Imaging Sci, Bldg 10, Bethesda, MD 20892 USA. EM mingchen.gao@nih.gov NR 19 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER INT PUBLISHING AG PI CHAM PA GEWERBESTRASSE 11, CHAM, CH-6330, SWITZERLAND SN 0302-9743 BN 978-3-319-47157-0; 978-3-319-47156-3 J9 LECT NOTES COMPUT SC PY 2016 VL 10019 BP 147 EP 155 DI 10.1007/978-3-319-47157-0_18 PG 9 WC Computer Science, Artificial Intelligence; Computer Science, Theory & Methods; Radiology, Nuclear Medicine & Medical Imaging SC Computer Science; Radiology, Nuclear Medicine & Medical Imaging GA BG6CJ UT WOS:000389945100018 ER PT S AU Kohanski, RA Deeks, SG Gravekamp, C Halter, JB High, K Hurria, A Fuldner, R Green, P Huebner, R Macchiarini, F Sierra, F AF Kohanski, Ronald A. Deeks, Steven G. Gravekamp, Claudia Halter, Jeffrey B. High, Kevin Hurria, Arti Fuldner, Rebecca Green, Paige Huebner, Robin Macchiarini, Francesca Sierra, Felipe GP NY Acad Sci BE Braaten, D TI Reverse geroscience: how does exposure to early diseases accelerate the age-related decline in health? SO ANNALS REPORTS, VOL 1386 SE Annals of the New York Academy of Sciences LA English DT Article; Book Chapter DE geroscience; aging; cancer; HIV; AIDS; diabetes ID QUALITY-OF-LIFE; GENOME-WIDE ASSOCIATION; RANDOMIZED CONTROLLED-TRIAL; MILD COGNITIVE IMPAIRMENT; METASTATIC BREAST-CANCER; BETA-CELL PROLIFERATION; HIV-INFECTION; INSULIN-RESISTANCE; SUPPRESSOR-CELLS; OLDER-ADULTS AB Aging is the major risk factor for both the development of chronic diseases and loss of functional capacity. Geroscience provides links among the biology of aging, the biology of disease, and the physiology of frailty, three fields where enormous progress has been made in the last few decades. While, previously, the focus was on the role of aging in susceptibility to disease and disability, the other side of this relationship, which is the contribution of disease to aging, has been less explored at the molecular/cellular level. Indeed, the role of childhood or early adulthood exposure to chronic disease and/or treatment on accelerating aging phenotypes is well known in epidemiology, but the biological basis is poorly understood. A recent summit co-organized by the National Institutes of Health GeroScience Interest Group and the New York Academy of Sciences explored these relationships, using three chronic diseases as examples: cancer, HIV/AIDS, and diabetes. The epidemiological literature clearly indicates that early exposure to any of these diseases and/or their treatments results in an acceleration of the appearance of aging phenotypes, including loss of functional capacity and accelerated appearance of clinical symptoms of aging-related diseases not obviously related to the earlier event. The discussions at the summit focused on the molecular and cellular relationships between each of these diseases and the recently defined molecular and cellular pillars of aging. Two major conclusions from the meeting include the desire to refine an operational definition of aging and to concomitantly develop biomarkers of aging, in order to move from chronological to physiological age. The discussion also opened a dialogue on the possibility of improving late-life outcomes in patients affected by chronic disease by including age-delaying modalities along with the standard care for the disease in question. C1 [Kohanski, Ronald A.; Fuldner, Rebecca; Macchiarini, Francesca; Sierra, Felipe] NIA, Div Aging Biol, NIH, Bethesda, MD 20892 USA. [Deeks, Steven G.] Univ Calif San Francisco, Dept Med, San Francisco, CA USA. [Gravekamp, Claudia] Albert Einstein Coll Med, Dept Microbiol & Immunol, Bronx, NY 10467 USA. [Halter, Jeffrey B.] Univ Michigan, Geriatr Ctr, Ann Arbor, MI 48109 USA. [Halter, Jeffrey B.] Univ Michigan, Inst Gerontol, Ann Arbor, MI 48109 USA. [High, Kevin] Wake Forest Sch Med, Infect Dis Sect, Dept Internal Med, Winston Salem, NC USA. [Hurria, Arti] City Hope Natl Med Ctr, Comprehens Canc Ctr, Duarte, CA USA. [Hurria, Arti] Beckman Res Inst, Duarte, CA USA. [Green, Paige] NCI, Biobehav & Psychol Branch, NIH, Bethesda, MD 20892 USA. [Huebner, Robin] NIAID, Div Aids, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA. RP Sierra, F (reprint author), NIA, Div Aging Biol, NIH, Bethesda, MD 20892 USA. EM sierraf@nia.nih.gov NR 138 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL SCIENCE PUBL PI OXFORD PA OSNEY MEAD, OXFORD OX2 0EL, ENGLAND SN 0077-8923 J9 ANN NY ACAD SCI JI Ann.NY Acad.Sci. PY 2016 VL 1386 BP 30 EP 44 DI 10.1111/nyas.13297 PG 15 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA BG9XT UT WOS:000394090800003 PM 27907230 ER PT S AU Hodes, RJ Sierra, F Austad, SN Epel, E Neigh, GN Erlandson, KM Schafer, MJ LeBrasseur, NK Wiley, C Campisi, J Sehl, ME Scalia, R Eguchi, S Kasinath, BS Halter, JB Cohen, HJ Demark-Wahnefried, W Ahles, TA Barzilai, N Hurria, A Hunt, PW AF Hodes, Richard J. Sierra, Felipe Austad, Steven N. Epel, Elissa Neigh, Gretchen N. Erlandson, Kristine M. Schafer, Marissa J. LeBrasseur, Nathan K. Wiley, Christopher Campisi, Judith Sehl, Mary E. Scalia, Rosario Eguchi, Satoru Kasinath, Balakuntalam S. Halter, Jeffrey B. Cohen, Harvey Jay Demark-Wahnefried, Wendy Ahles, Tim A. Barzilai, Nir Hurria, Arti Hunt, Peter W. GP NY Acad Sci BE Braaten, D TI Disease drivers of aging SO ANNALS REPORTS, VOL 1386 SE Annals of the New York Academy of Sciences LA English DT Article; Book Chapter DE disease; aging; pathology; chronic; prevention; age-related; HIV; diabetes; cancer ID QUALITY-OF-LIFE; BETA-CELL PROLIFERATION; TERM CANCER SURVIVORS; CHRONIC HIV-INFECTION; INSULIN-RESISTANCE; NITRIC-OXIDE; ENDOTHELIAL DYSFUNCTION; ISCHEMIA-REPERFUSION; HYDROGEN-SULFIDE; OXIDATIVE-STRESS AB It has long been known that aging, at both the cellular and organismal levels, contributes to the development and progression of the pathology of many chronic diseases. However, much less research has examined the inverse relationship-the contribution of chronic diseases and their treatments to the progression of aging-related phenotypes. Here, we discuss the impact of three chronic diseases (cancer, HIV/AIDS, and diabetes) and their treatments on aging, putative mechanisms by which these effects are mediated, and the open questions and future research directions required to understand the relationships between these diseases and aging. C1 [Hodes, Richard J.; Sierra, Felipe] NIA, Bethesda, MD 20892 USA. [Austad, Steven N.] Univ Alabama Birmingham, Dept Biol, Birmingham, AL 35294 USA. [Epel, Elissa] Univ Calif San Francisco, Dept Psychiat, San Francisco, CA USA. [Neigh, Gretchen N.] Virginia Commonwealth Univ, Richmond, VA USA. [Erlandson, Kristine M.] Univ Colorado, Anschutz Med Ctr, Aurora, CO USA. [Schafer, Marissa J.; LeBrasseur, Nathan K.] Mayo Clin, Coll Med, Robert & Arlene Kogod Ctr Aging, Rochester, MN USA. [Schafer, Marissa J.; LeBrasseur, Nathan K.] Mayo Clin, Coll Med, Dept Phys Med & Rehabil, Rochester, MN USA. [Wiley, Christopher; Campisi, Judith] Buck Inst Res Aging, Novato, CA USA. [Sehl, Mary E.] Univ Calif Los Angeles, David Geffen Sch Med, Los Angeles, CA 90095 USA. [Scalia, Rosario; Eguchi, Satoru] Temple Univ, Lewis Katz Sch Med, Dept Physiol, Philadelphia, PA 19122 USA. [Scalia, Rosario; Eguchi, Satoru] Temple Univ, Lewis Katz Sch Med, Cardiovasc Res Ctr, Philadelphia, PA 19122 USA. [Kasinath, Balakuntalam S.] Univ Texas Hlth Sci Ctr San Antonio, South Texas Vet Hlth Care Syst, Barshop Inst Longev & Aging Studies, San Antonio, TX 78229 USA. [Halter, Jeffrey B.] Univ Michigan, Div Geriatr & Palliat Med, Ann Arbor, MI 48109 USA. [Cohen, Harvey Jay] Duke Univ, Sch Med, Durham, NC USA. [Demark-Wahnefried, Wendy] Univ Alabama Birmingham, Ctr Comprehens Canc, Birmingham, AL 35294 USA. [Ahles, Tim A.] Mem Sloan Kettering Canc Ctr, 1275 York Ave, New York, NY 10021 USA. [Barzilai, Nir] Albert Einstein Coll Med, Inst Aging Res, New York, NY USA. [Hurria, Arti] City Hope Natl Med Ctr, Natl Med Ctr, Duarte, CA USA. [Hunt, Peter W.] Univ Calif San Francisco, Sch Med, San Francisco, CA USA. RP Hodes, RJ (reprint author), NIA, Bethesda, MD 20892 USA. EM annals@nyas.org FU NIA NIH HHS [K23 AG050260]; NIDDK NIH HHS [P30 DK079626] NR 160 TC 1 Z9 1 U1 2 U2 2 PU BLACKWELL SCIENCE PUBL PI OXFORD PA OSNEY MEAD, OXFORD OX2 0EL, ENGLAND SN 0077-8923 J9 ANN NY ACAD SCI JI Ann.NY Acad.Sci. PY 2016 VL 1386 BP 45 EP 68 DI 10.1111/nyas.13299 PG 24 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA BG9XT UT WOS:000394090800004 PM 27943360 ER PT J AU Bertocchi, C Wang, Y Ravasio, A Hara, Y Wu, Y Sailov, T Baird, MA Davidson, MW Zaidel-Bar, R Toyama, Y Ladoux, B Mege, R Kanchanawong, P AF Bertocchi, C. Wang, Y. Ravasio, A. Hara, Y. Wu, Y. Sailov, T. Baird, M. A. Davidson, M. W. Zaidel-Bar, R. Toyama, Y. Ladoux, B. Mege, R. Kanchanawong, P. TI Nanoscale architecture of cadherin-based cell adhesions. SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 [Bertocchi, C.; Wang, Y.; Ravasio, A.; Hara, Y.; Wu, Y.; Zaidel-Bar, R.; Toyama, Y.; Ladoux, B.; Kanchanawong, P.] Natl Univ Singapore, Mechanobiol Inst, Singapore, Singapore. [Sailov, T.] Nanyang Technol Univ, Singapore Ctr Environm Life Sci Engn, Singapore, Singapore. [Baird, M. A.] NHLBI, NIH, Bldg 10, Bethesda, MD 20892 USA. [Davidson, M. W.] Florida State Univ, Natl High Magnet Field Lab, Tallahassee, FL 32306 USA. [Davidson, M. W.] Florida State Univ, Dept Biol Sci, B-157, Tallahassee, FL 32306 USA. [Zaidel-Bar, R.; Kanchanawong, P.] Natl Univ Singapore, Dept Biomed Engn, Singapore, Singapore. [Toyama, Y.] Natl Univ Singapore, Dept Biol Sci, Singapore, Singapore. [Toyama, Y.] Natl Univ Singapore, Temasek Life Sci Lab, Singapore, Singapore. [Ladoux, B.; Mege, R.] Univ Paris Diderot, Inst Jacques Monod, Paris, France. [Ladoux, B.; Mege, R.] CNRS, Paris, France. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 EI 1939-4586 J9 MOL BIOL CELL JI Mol. Biol. Cell PY 2016 VL 27 MA M158 PG 2 WC Cell Biology SC Cell Biology GA EK9QR UT WOS:000394259500292 ER PT J AU Gurel, PS Kim, LY Omabegho, T Bryant, Z Alushin, GM AF Gurel, P. S. Kim, L. Y. Omabegho, T. Bryant, Z. Alushin, G. M. TI High-resolution structural characterization of the myosin VI-F-actin interface during the force generation cycle. SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 [Gurel, P. S.; Kim, L. Y.; Alushin, G. M.] NHLBI, Cell Biol & Physiol Ctr, Bethesda, MD 20892 USA. [Omabegho, T.; Bryant, Z.] Stanford Univ, Sch Med, Dept Bioengn, Stanford, CA 94305 USA. [Omabegho, T.; Bryant, Z.] Stanford Univ, Sch Med, Dept Biol Struct, Stanford, CA 94305 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 EI 1939-4586 J9 MOL BIOL CELL JI Mol. Biol. Cell PY 2016 VL 27 MA E51 PG 2 WC Cell Biology SC Cell Biology GA EK9QR UT WOS:000394259500127 ER PT J AU Iglesias-Bartolome, R AF Iglesias-Bartolome, R. TI A Galpha-s/PKA tumor suppressor pathway restraining YAP1 and GLI in epithelial stem cells. SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 [Iglesias-Bartolome, R.] NCI, LCMB, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 EI 1939-4586 J9 MOL BIOL CELL JI Mol. Biol. Cell PY 2016 VL 27 MA M225 PG 1 WC Cell Biology SC Cell Biology GA EK9QR UT WOS:000394259500416 ER PT J AU Jaumouille, V Liu, T Betzig, E Waterman, CM AF Jaumouille, V. Liu, T. Betzig, E. Waterman, C. M. TI beta 2 integrins mediate the formation of a focal adhesion-like cytoskeleton and signaling platform during phagocytosis. SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 [Jaumouille, V.; Waterman, C. M.] NHLBI, NIH, Bldg 10, Bethesda, MD 20892 USA. [Liu, T.; Betzig, E.] Howard Hughes Med Inst, Janelia Res Campus, Ashburn, VA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 EI 1939-4586 J9 MOL BIOL CELL JI Mol. Biol. Cell PY 2016 VL 27 MA E132 PG 2 WC Cell Biology SC Cell Biology GA EK9QR UT WOS:000394259500358 ER PT J AU Joshi, AS Huang, X Choudhary, V Levine, T Hu, J Prinz, W AF Joshi, A. S. Huang, X. Choudhary, V. Levine, T. Hu, J. Prinz, W. TI A family of membrane-shaping proteins generates ER subdomains that mediate pre-peroxisomal vesicle biogenesis. SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 [Joshi, A. S.; Choudhary, V.; Prinz, W.] NIDDK, NIH, Bethesda, MD 20892 USA. [Huang, X.; Hu, J.] Nankai Univ, Dept Genet & Cell Biol, Tianjin, Peoples R China. [Huang, X.; Hu, J.] Tianjin Key Lab Prot Sci, Tianjin, Peoples R China. [Levine, T.] UCL, Inst Opthalmol, London, England. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 EI 1939-4586 J9 MOL BIOL CELL JI Mol. Biol. Cell PY 2016 VL 27 MA M119 PG 1 WC Cell Biology SC Cell Biology GA EK9QR UT WOS:000394259500187 ER PT J AU Malide, D Sun, N Finkel, T AF Malide, D. Sun, N. Finkel, T. TI Illuminating mitophagy in living mt-Keima mouse tissues via STED super-resolution microscopy. SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 [Malide, D.] NHLBI, Light Microscopy Core, NIH, Bldg 10, Bethesda, MD 20892 USA. [Sun, N.; Finkel, T.] NHLBI, Ctr Mol Med, NIH, Bldg 10, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 EI 1939-4586 J9 MOL BIOL CELL JI Mol. Biol. Cell PY 2016 VL 27 MA E34 PG 2 WC Cell Biology SC Cell Biology GA EK9QR UT WOS:000394259500110 ER PT J AU Mehta, GD Ball, DA Salomon-Kent, R Mazza, D Morisaki, T Mueller, F McNally, JG Karpova, TS AF Mehta, G. D. Ball, D. A. Salomon-Kent, R. Mazza, D. Morisaki, T. Mueller, F. McNally, J. G. Karpova, T. S. TI Single Molecule Tracking of Ace1p In Saccharomyces cerevisiae defines a characteristic residence time for non-specific interactions of transcription factors with chromatin. SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 [Mehta, G. D.; Ball, D. A.; Salomon-Kent, R.; Karpova, T. S.] NIH, Lab Receptor Biol & Gene Express, Bldg 10, Bethesda, MD 20892 USA. [Mazza, D.] Ctr Imaging Sperimentale, Milan, Italy. [Mazza, D.] Univ Vita Salute San Raffaele, Ist Sci Osped San Raffaele, Milan, Italy. [Morisaki, T.] Colorado State Univ, Dept Biochem & Mol Biol, Ft Collins, CO 80523 USA. [Mueller, F.] Inst Pasteur, CNRS, Computat Imaging & Modeling Unit, Paris, France. [McNally, J. G.] Helmholtz Ctr Berlin, Inst Soft Matter & Funct Mat, Berlin, Germany. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 EI 1939-4586 J9 MOL BIOL CELL JI Mol. Biol. Cell PY 2016 VL 27 MA E16 PG 1 WC Cell Biology SC Cell Biology GA EK9QR UT WOS:000394259500092 ER PT J AU Meseroll, RA Holay, N Caridi, C Bachant, J Cohen-Fix, O AF Meseroll, R. A. Holay, N. Caridi, C. Bachant, J. Cohen-Fix, O. TI A novel role for the essential DNA topoisomerase, Top2, in nuclear morphology and chromatin organization. SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 [Meseroll, R. A.; Holay, N.; Cohen-Fix, O.] NIDDK, NIH, Bethesda, MD 20892 USA. [Caridi, C.; Bachant, J.] Univ Calif Riverside, Grad Program Cell & Mol Biol, Riverside, CA 92521 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 EI 1939-4586 J9 MOL BIOL CELL JI Mol. Biol. Cell PY 2016 VL 27 MA E39 PG 1 WC Cell Biology SC Cell Biology GA EK9QR UT WOS:000394259500115 ER PT J AU Rodriguez, J Chow, CC Larson, DR AF Rodriguez, J. Chow, C. C. Larson, D. R. TI Regulation of estrogen-responsive genes in single human cells. SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 [Rodriguez, J.; Larson, D. R.] NCI, Lab Receptor Biol Gene Express, Bethesda, MD 20892 USA. [Chow, C. C.] NIDDK, Lab Biol Modeling, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 EI 1939-4586 J9 MOL BIOL CELL JI Mol. Biol. Cell PY 2016 VL 27 MA M180 PG 1 WC Cell Biology SC Cell Biology GA EK9QR UT WOS:000394259500314 ER PT J AU Skau, CT Fischer, RS Gurel, PS Thiam, HR Tubbs, A Baird, MA Davidson, MW Piel, M Alushin, GM Nussenzweig, A Steeg, PS Waterman, CM AF Skau, C. T. Fischer, R. S. Gurel, P. S. Thiam, H. R. Tubbs, A. Baird, M. A. Davidson, M. W. Piel, M. Alushin, G. M. Nussenzweig, A. Steeg, P. S. Waterman, C. M. TI FMN2 is a melanoma metastasis-promoter that mediates formation of a perinuclear actin/adhesion system to protect nuclei and DNA from damage during confined cell migration. SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 [Skau, C. T.; Fischer, R. S.; Gurel, P. S.; Thiam, H. R.; Baird, M. A.; Alushin, G. M.; Waterman, C. M.] NHLBI, Cell Biol & Physiol Ctr, NIH, Bldg 10, Bethesda, MD 20892 USA. [Thiam, H. R.; Piel, M.] Inst Curie, CNRS, UMR 144, Paris, France. [Tubbs, A.; Nussenzweig, A.] NCI, Lab Genome Integr, NIH, Bethesda, MD 20892 USA. [Baird, M. A.; Davidson, M. W.] Florida State Univ, Magnet Lab, Tallahassee, FL 32306 USA. [Steeg, P. S.] NCI, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 EI 1939-4586 J9 MOL BIOL CELL JI Mol. Biol. Cell PY 2016 VL 27 MA M215 PG 1 WC Cell Biology SC Cell Biology GA EK9QR UT WOS:000394259500406 ER PT J AU Swaminathan, V Mathew, JK Mehta, S Nordenfelt, P Moore, TI Nobuyasu, K Baker, D Oldenbourg, R Tani, T Mayor, S Springer, TA Waterman, CM AF Swaminathan, V. Mathew, J. K. Mehta, S. Nordenfelt, P. Moore, T. I. Nobuyasu, K. Baker, D. Oldenbourg, R. Tani, T. Mayor, S. Springer, T. A. Waterman, C. M. TI Actin retrograde flow actively aligns and orients ligand-engaged integrins in focal adhesions. SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 [Swaminathan, V.; Waterman, C. M.] NHLBI, Cell Biol & Physiol Ctr, NIH, Bldg 10, Bethesda, MD 20892 USA. [Mathew, J. K.; Mayor, S.] Natl Ctr Biol Sci, Bangalore, Karnataka, India. [Mehta, S.; Oldenbourg, R.; Tani, T.] Marine Biol Sci, Woods Hole, MA USA. [Nordenfelt, P.] Lund Univ, Div Infect Med, Lund, MD USA. [Moore, T. I.; Springer, T. A.] Harvard Univ, Program Cellular & Mol Med, Boston, MA 02115 USA. [Nobuyasu, K.; Baker, D.] Univ Washington, Dept Biochem, Seattle, WA 98195 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 EI 1939-4586 J9 MOL BIOL CELL JI Mol. Biol. Cell PY 2016 VL 27 MA E58 PG 1 WC Cell Biology SC Cell Biology GA EK9QR UT WOS:000394259500202 ER PT J AU Vecchiarelli, AG Mizuuchi, K AF Vecchiarelli, A. G. Mizuuchi, K. TI Mechanistic insights of the Min Oscillator via cell-free reconstitution and imaging. SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 [Vecchiarelli, A. G.; Mizuuchi, K.] NIH, Bldg 10, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 EI 1939-4586 J9 MOL BIOL CELL JI Mol. Biol. Cell PY 2016 VL 27 MA M6 PG 1 WC Cell Biology SC Cell Biology GA EK9QR UT WOS:000394259500012 ER PT J AU Vemu, A Atherton, J Spector, JO Moores, CA Roll-Mecak, A AF Vemu, A. Atherton, J. Spector, J. O. Moores, C. A. Roll-Mecak, A. TI Tubulin isoform composition tunes microtubule dynamics SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 [Vemu, A.; Spector, J. O.; Roll-Mecak, A.] NINDS, NIH, Bldg 36,Rm 4D04, Bethesda, MD 20892 USA. [Atherton, J.; Moores, C. A.] Univ London Birkbeck Coll, Dept Biol Sci, London, England. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 EI 1939-4586 J9 MOL BIOL CELL JI Mol. Biol. Cell PY 2016 VL 27 MA M42 PG 1 WC Cell Biology SC Cell Biology GA EK9QR UT WOS:000394259500048 ER PT J AU Walia, V Vetter, M Insinna, C Lu, Q Ritt, D Specht, S Stauffer, J Morrison, D Lorentzen, E Westlake, CJ AF Walia, V. Vetter, M. Insinna, C. Lu, Q. Ritt, D. Specht, S. Stauffer, J. Morrison, D. Lorentzen, E. Westlake, C. J. TI Growth factor signaling regulation of a Rab-effector switch required for ciliogenesis initiation. SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 [Walia, V.; Insinna, C.; Lu, Q.; Ritt, D.; Specht, S.; Stauffer, J.; Morrison, D.; Westlake, C. J.] NCI, Ctr Canc Res, Frederick, MD 21701 USA. [Vetter, M.; Lorentzen, E.] Max Plank Inst Biochem, Martinsried, Germany. NR 0 TC 0 Z9 0 U1 1 U2 1 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 EI 1939-4586 J9 MOL BIOL CELL JI Mol. Biol. Cell PY 2016 VL 27 MA E104 PG 1 WC Cell Biology SC Cell Biology GA EK9QR UT WOS:000394259500247 ER PT J AU Wang, JT Hoerner, C Kong, D Loncarek, J Stearns, T AF Wang, J. T. Hoerner, C. Kong, D. Loncarek, J. Stearns, T. TI Epsilon-tubulin deletion in human cells results in loss of centrioles and a futile procentriole formation/disintegration cycle. SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 [Wang, J. T.; Hoerner, C.; Stearns, T.] Stanford Univ, Dept Biol, Stanford, CA 94305 USA. [Hoerner, C.] Stanford Sch Med, Dept Med, Div Oncol, Stanford, CA USA. [Kong, D.; Loncarek, J.] NCI, Lab Prot Dynam & Signaling, Ctr Canc Res Frederick, NIH, Frederick, MD 21701 USA. [Stearns, T.] Stanford Sch Med, Dept Genet, Stanford, CA USA. NR 6 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 EI 1939-4586 J9 MOL BIOL CELL JI Mol. Biol. Cell PY 2016 VL 27 MA M207 PG 2 WC Cell Biology SC Cell Biology GA EK9QR UT WOS:000394259500398 ER PT J AU Wu, Z Plotnikov, SV Moalim, AY Waterman, CM Liu, J AF Wu, Z. Plotnikov, S. V. Moalim, A. Y. Waterman, C. M. Liu, J. TI Two distinct actin networks mediate traction oscillations to confer mechanosensitivity of focal adhesions. SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 [Wu, Z.; Waterman, C. M.; Liu, J.] NHLBI, NIH, Bldg 10, Bethesda, MD 20892 USA. [Plotnikov, S. V.; Moalim, A. Y.] Univ Toronto, Dept Cell Syst Biol, Toronto, ON, Canada. NR 0 TC 0 Z9 0 U1 1 U2 1 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 EI 1939-4586 J9 MOL BIOL CELL JI Mol. Biol. Cell PY 2016 VL 27 MA E57 PG 1 WC Cell Biology SC Cell Biology GA EK9QR UT WOS:000394259500201 ER PT J AU Paz-Y-Mino, C Sacoto, MJG Leone, PE AF Paz-y-Mino, Cesar Sacoto, Maria J. Guillen Leone, Paola E. TI Genetics and genomic medicine in Ecuador SO MOLECULAR GENETICS & GENOMIC MEDICINE LA English DT Article ID CHRONIC MYELOGENOUS LEUKEMIA; CHRONIC MYELOID-LEUKEMIA; PATHOLOGICAL CHARACTERISTICS; CHROMOSOME-ABERRATIONS; POPULATION HISTORY; PROSTATE-CANCER; SOUTH-AMERICA; RISK-FACTOR; DNA-DAMAGE; HMSH2 GENE C1 [Paz-y-Mino, Cesar; Leone, Paola E.] Univ Las Amer, Inst Invest Biomed, Quito, Ecuador. [Sacoto, Maria J. Guillen] NHGRI, NIH, Bethesda, MD 20892 USA. RP Paz-Y-Mino, C (reprint author), Univ Las Amer, Inst Invest Biomed, Quito, Ecuador. NR 73 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 2324-9269 J9 MOL GENET GENOM MED JI Mol. Genet. Genom. Med. PD JAN PY 2016 VL 4 IS 1 BP 9 EP 17 DI 10.1002/mgg3.192 PG 9 WC Genetics & Heredity SC Genetics & Heredity GA EJ7NU UT WOS:000393409900002 PM 26788533 ER PT J AU Boone, PM Yuan, B Gu, S Ma, ZW Gambin, T Gonzaga-Jauregui, C Jain, M Murdock, TJ White, JJ Jhangiani, SN Walker, K Wang, QY Muzny, DM Gibbs, RA Hejtmancik, JF Lupski, JR Posey, JE Lewis, RA AF Boone, Philip M. Yuan, Bo Gu, Shen Ma, Zhiwei Gambin, Tomasz Gonzaga-Jauregui, Claudia Jain, Mahim Murdock, Todd J. White, Janson J. Jhangiani, Shalini N. Walker, Kimberly Wang, Qiaoyan Muzny, Donna M. Gibbs, Richard A. Hejtmancik, J. Fielding Lupski, James R. Posey, Jennifer E. Lewis, Richard A. TI Hutterite-type cataract maps to chromosome 6p21.32-p21.31, cosegregates with a homozygous mutation in LEMD2, and is associated with sudden cardiac death SO MOLECULAR GENETICS & GENOMIC MEDICINE LA English DT Article DE Cataract; Hutterite; LEM domain; LEMD2; MUC21; recessive; sudden death ID NUCLEAR-MEMBRANE PROTEIN; MAJOR HISTOCOMPATIBILITY COMPLEX; MUSCULAR-DYSTROPHY; JUVENILE CATARACT; POLYPEPTIDE 2; CELL; ENVELOPE; LAMINA; EMERIN; LENS AB Background Juvenile-onset cataracts are known among the Hutterites of North America. Despite being identified over 30 years ago, this autosomal recessive condition has not been mapped, and the disease gene is unknown. Methods We performed whole exome sequencing of three Hutterite-type cataract trios and follow-up genotyping and mapping in four extended kindreds. Results Trio exomes enabled genome-wide autozygosity mapping, which localized the disease gene to a 9.5-Mb region on chromosome 6p. This region contained two candidate variants, LEMD2 c.T38G and MUC21 c.665delC. Extended pedigrees recruited for variant genotyping revealed multiple additional relatives with juvenile-onset cataract, as well as six deceased relatives with both cataracts and sudden cardiac death. The candidate variants were genotyped in 84 family members, including 17 with cataracts; only the variant in LEMD2 cosegregated with cataracts (LOD = 9.62). SNP-based fine mapping within the 9.5 Mb linked region supported this finding by refining the cataract locus to a 0.5- to 2.9-Mb subregion (6p21.32-p21.31) containing LEMD2 but not MUC21. LEMD2 is expressed in mouse and human lenses and encodes a LEM domain-containing protein; the c.T38G missense mutation is predicted to mutate a highly conserved residue within this domain (p.Leu13Arg). Conclusion We performed a genetic and genomic study of Hutterite-type cataract and found evidence for an association of this phenotype with sudden cardiac death. Using combined genetic and genomic approaches, we mapped cataracts to a small portion of chromosome 6 and propose that they result from a homozygous missense mutation in LEMD2. C1 [Boone, Philip M.; Yuan, Bo; Gu, Shen; Gambin, Tomasz; Gonzaga-Jauregui, Claudia; Jain, Mahim; White, Janson J.; Gibbs, Richard A.; Lupski, James R.; Posey, Jennifer E.; Lewis, Richard A.] Baylor Coll Med, Dept Mol & Human Genet, Houston, TX 77030 USA. [Ma, Zhiwei; Hejtmancik, J. Fielding] NEI, Ophthalm Genet & Visual Funct Branch, Rockville, MD USA. [Murdock, Todd J.] Rocky Mt Eye Ctr, Missoula, MT USA. [Jhangiani, Shalini N.; Walker, Kimberly; Wang, Qiaoyan; Muzny, Donna M.; Gibbs, Richard A.] Baylor Coll Med, Human Genome Sequencing Ctr, Houston, TX 77030 USA. [Lupski, James R.; Lewis, Richard A.] Baylor Coll Med, Dept Pediat, Houston, TX 77030 USA. [Lupski, James R.; Lewis, Richard A.] Texas Childrens Hosp, Houston, TX USA. [Lewis, Richard A.] Baylor Coll Med, Dept Ophthalmol, Houston, TX 77030 USA. [Lewis, Richard A.] Baylor Coll Med, Dept Med, Houston, TX 77030 USA. RP Lewis, RA (reprint author), Baylor Coll Med, Neurosensory Ctr, Dept Ophthalmol Pediat, Room NC 226,MS NC205,One Baylor Plaza, Houston, TX 77030 USA.; Lewis, RA (reprint author), Baylor Coll Med, Neurosensory Ctr, Dept Mol & Human Genet, Room NC 226,MS NC205,One Baylor Plaza, Houston, TX 77030 USA. EM rlewis@bcm.edu OI Boone, Philip/0000-0001-9528-252X; Gonzaga-Jauregui, Claudia/0000-0002-4667-3679 FU Baylor College of Medicine Medical Scientist Training Program [T32GM007330]; National Eye Institute (NEI) Training Program grant from the United States National Institutes of Health (NIH) [T32EY007102]; Wintermann Foundation; Baylor Research Advocates for Student Scientists; National Institute of General Medical Sciences (NIGMS) Medical Genetics Research Fellowship Program [T32GM0752637]; Research to Prevent Blindness, New York; National Human Genome Research Institute and National Heart Lung and Blood Institute (NHGRI/NHLBI) [U54HG006542]; NHGRI [U54HG003273] FX P.M.B. received support from the Baylor College of Medicine Medical Scientist Training Program (T32GM007330), a National Eye Institute (NEI) Training Program grant (T32EY007102) from the United States National Institutes of Health (NIH), and grants from the Wintermann Foundation and the Baylor Research Advocates for Student Scientists. J.E.P. and M.J. were supported by the National Institute of General Medical Sciences (NIGMS) Medical Genetics Research Fellowship Program (T32GM0752637). R.A.L. is a Senior Scientific Investigator of Research to Prevent Blindness, New York, whose unrestricted funds supported parts of these investigations. This work was supported in part by the National Human Genome Research Institute and National Heart Lung and Blood Institute (NHGRI/NHLBI) to the Baylor-Hopkins Center for Mendelian Genomics (U54HG006542) and NHGRI (U54HG003273). NR 62 TC 1 Z9 1 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 2324-9269 J9 MOL GENET GENOM MED JI Mol. Genet. Genom. Med. PD JAN PY 2016 VL 4 IS 1 BP 77 EP 94 DI 10.1002/mgg3.181 PG 18 WC Genetics & Heredity SC Genetics & Heredity GA EJ7NU UT WOS:000393409900008 PM 26788539 ER PT J AU Marangoni, D Bush, RA Zeng, Y Wei, LSL Ziccardi, L Vijayasarathy, C Bartoe, JT Palyada, K Santos, M Hiriyanna, S Wu, ZJ Colosi, P Sieving, PA AF Marangoni, Dario Bush, Ronald A. Zeng, Yong Wei, Lisa L. Ziccardi, Lucia Vijayasarathy, Camasamudram Bartoe, Joshua T. Palyada, Kiran Santos, Maria Hiriyanna, Suja Wu, Zhijian Colosi, Peter Sieving, Paul A. TI Ocular and systemic safety of a recombinant AAV8 vector for X-linked retinoschisis gene therapy: GLP studies in rabbits and Rs1-KO mice SO MOLECULAR THERAPY-METHODS & CLINICAL DEVELOPMENT LA English DT Article ID JUVENILE RETINOSCHISIS; MOUSE MODEL; RESCUE; CELLS AB X-linked retinoschisis (XLRS) is a retinal disease caused by mutations in the gene encoding the protein retinoschisin (RS1) and is one of the most common causes of macular degeneration in young men. Our therapeutic approach for XLRS is based on the administration of AAV8-scRS/IRBPhRS, an adeno-associated viral vector coding the human RS1 protein, via the intravitreal (IVT) route. Two Good Laboratory Practice studies, a 9-month study in New Zealand White rabbits (n = 124) injected with AAV8-scRS/IRBPhRS at doses of 2E9, 2E10, 2E11, and 1.5E12 vector genomes/eye (vg/eye), and a 6-month study in Rs1-KO mice (n = 162) dosed with 2E9 and 2E10 vg/eye of the same vector were conducted to assess ocular and systemic safety. A self-resolving, dose-dependent vitreal inflammation was the main ocular finding, and except for a single rabbit dosed with 1.5E12 vg/eye, which showed a retinal detachment, no other ocular adverse event was reported. Systemic toxicity was not identified in either species. Biodistribution analysis in Rs1-KO mice detected spread of vector genome in extraocular tissues, but no evidence of organ or tissues damage was found. These studies indicate that IVT administration of AAV8-scRS/IRBPhRS is safe and well tolerated and support its advancement into a phase 1/2a clinical trial for XLRS. C1 [Marangoni, Dario; Bush, Ronald A.; Zeng, Yong; Ziccardi, Lucia; Vijayasarathy, Camasamudram; Santos, Maria; Sieving, Paul A.] NIDCD, NIH, Bethesda, MD 20892 USA. [Marangoni, Dario] Univ Aquila, Dept Biotechnol & Appl Clin Sci, Laquila, Italy. [Wei, Lisa L.; Hiriyanna, Suja; Wu, Zhijian; Colosi, Peter; Sieving, Paul A.] NEI, NIH, Bethesda, MD 20892 USA. [Ziccardi, Lucia] GB Bietti Fdn, IRCCS, Dept Neurophysiol Vis & Neurophthalmol, Rome, Italy. [Bartoe, Joshua T.; Palyada, Kiran] MPI Res, Mattawan, MI USA. [Palyada, Kiran] Merck Res Lab, Kenilworth, NJ USA. [Colosi, Peter] BioMarin Pharmaceut Inc, Novato, CA USA. RP Sieving, PA (reprint author), NIDCD, NIH, Bethesda, MD 20892 USA.; Sieving, PA (reprint author), NEI, NIH, Bethesda, MD 20892 USA. EM paulsieving@nei.nih.gov FU Intramural Research Program of the National Eye Institute; National Institute on Deafness and Other Communication Disorders FX This study was supported by the Intramural Research Program of the National Eye Institute and National Institute on Deafness and Other Communication Disorders. NR 24 TC 0 Z9 0 U1 0 U2 0 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 2329-0501 J9 MOL THER-METH CLIN D JI Mol.Ther.-Methods Clin. Dev. PY 2016 VL 3 AR UNSP 16011 DI 10.1038/mtm.2016.11 PG 13 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA EJ8DM UT WOS:000393455200022 ER PT J AU Nasimuzzaman, M Lynn, D Ernst, R Beuerlein, M Smith, RH Shrestha, A Cross, S Link, K Lutzko, C Nordling, D Russell, DW Larochelle, A Malik, P Van der Loo, JCM AF Nasimuzzaman, Md Lynn, Danielle Ernst, Rebecca Beuerlein, Michele Smith, Richard H. Shrestha, Archana Cross, Scott Link, Kevin Lutzko, Carolyn Nordling, Diana Russell, David W. Larochelle, Andre Malik, Punam Van der Loo, Johannes C. M. TI Production and purification of high-titer foamy virus vector for the treatment of leukocyte adhesion deficiency SO MOLECULAR THERAPY-METHODS & CLINICAL DEVELOPMENT LA English DT Article ID CHRONIC GRANULOMATOUS-DISEASE; LENTIVIRAL VECTORS; GENE-THERAPY; RETROVIRAL VECTORS; HEPARAN-SULFATE; VIRAL VECTOR; CELLS; POLYETHYLENIMINE; CHROMATOGRAPHY; TRANSFECTION AB Compared to other integrating viral vectors, foamy virus (FV) vectors have distinct advantages as a gene transfer tool, including their nonpathogenicity, the ability to carry larger transgene cassettes, and increased stability of virus particles due to DNA genome formation within the virions. Proof of principle of its therapeutic utility was provided with the correction of canine leukocyte adhesion deficiency using autologous CD34(+) cells transduced with FV vector carrying the canine CD18 gene, demonstrating its long-term safety and efficacy. However, infectious titers of FV-human(h) CD18 were low and not suitable for manufacturing of clinical-grade product. Herein, we developed a scalable production and purification process that resulted in 60-fold higher FV-hCD18 titers from similar to 1.7 x 10(4) to 1.0 x 10(6) infectious units (IU)/ml. Process development improvements included use of polyethylenimine-based transfection, use of a codon-optimized gag, heparin affinity chromatography, tangential flow filtration, and ultracentrifugation, which reproducibly resulted in 5,000-fold concentrated and purified virus, an overall yield of 19 +/- 3%, and final titers of 1-2 x 10(9) IU/ml. Highly concentrated vector allowed reduction of final dimethyl sulfoxide (DMSO) concentration, thereby avoiding DMSO-induced toxicity to CD34(+) cells while maintaining high transduction efficiencies. This process development results in clinically relevant, high titer FV which can be scaled up for clinical grade production. C1 [Nasimuzzaman, Md; Lynn, Danielle; Ernst, Rebecca; Beuerlein, Michele; Shrestha, Archana; Cross, Scott; Link, Kevin; Lutzko, Carolyn; Nordling, Diana; Malik, Punam; Van der Loo, Johannes C. M.] Cincinnati Childrens Hosp Med Ctr, Div Expt Hematol & Canc Biol, Cincinnati, OH 45229 USA. [Nasimuzzaman, Md; Shrestha, Archana; Lutzko, Carolyn; Malik, Punam; Van der Loo, Johannes C. M.] Univ Cincinnati, Coll Med, Cincinnati, OH 45220 USA. [Smith, Richard H.; Larochelle, Andre] NHLBI, Hematol Branch, NIH, Bethesda, MD 20892 USA. [Cross, Scott] Florida Biologix, Alachua, FL USA. [Lutzko, Carolyn] Univ Cincinnati, Hoxworth Blood Ctr, Div Regenerat Med & Cellular Therapies, Cincinnati, OH USA. [Russell, David W.] Univ Washington, Div Hematol, Seattle, WA 98195 USA. [Van der Loo, Johannes C. M.] Childrens Hosp Philadelphia, Ctr Cellular & Mol Therapeut, Philadelphia, PA 19104 USA. RP Nasimuzzaman, M (reprint author), Cincinnati Childrens Hosp Med Ctr, Div Expt Hematol & Canc Biol, Cincinnati, OH 45229 USA.; Nasimuzzaman, M (reprint author), Univ Cincinnati, Coll Med, Cincinnati, OH 45220 USA. EM md.nasimuzzaman@cchmc.org FU intramural research program of the National Heart, Lung and Blood Institute (NHLBI) of the NIH; Translational Core Laboratories in the Cincinnati Children's Hospital Research Foundation; NHLBI [HL085107] FX This work was supported in part by the intramural research program of the National Heart, Lung and Blood Institute (NHLBI) of the NIH, and intramural funds available to the Translational Core Laboratories in the Cincinnati Children's Hospital Research Foundation. D.R. was supported by grant HL085107 from NHLBI. NR 40 TC 0 Z9 0 U1 0 U2 0 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 2329-0501 J9 MOL THER-METH CLIN D JI Mol.Ther.-Methods Clin. Dev. PY 2016 VL 3 AR UNSP 16004 DI 10.1038/mtm.2016.4 PG 8 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA EJ8DM UT WOS:000393455200015 PM 27722179 ER PT J AU Uchida, N Weitzel, RP Shvygin, A Skala, LP Raines, L Bonifacino, AC Krouse, AE Metzger, ME Donahue, RE Tisdale, JF AF Uchida, Naoya Weitzel, R. Patrick Shvygin, Anna Skala, Luke P. Raines, Lydia Bonifacino, Aylin C. Krouse, Allen E. Metzger, Mark E. Donahue, Robert E. Tisdale, John F. TI Total body irradiation must be delivered at high dose for efficient engraftment and tolerance in a rhesus stem cell gene therapy model SO MOLECULAR THERAPY-METHODS & CLINICAL DEVELOPMENT LA English DT Article ID LENTIVIRAL VECTOR; IN-VIVO; IMMUNOLOGICAL-TOLERANCE; TRANSPLANTATION; IMMUNODEFICIENCY; TRANSDUCTION; ACTIVATION; DISEASE AB Reduced intensity conditioning (RIC) is desirable for hematopoietic stem cell (HSC) gene therapy applications. However, low gene marking was previously observed in gene therapy trials, suggesting that RIC might be insufficient for (i) opening niches for efficient engraftment and/or (ii) inducing immunological tolerance for transgene-encoded proteins. Therefore, we evaluated both engraftment and tolerance for gene-modified cells using our rhesus HSC gene therapy model following RIC. We investigated a dose de-escalation of total body irradiation (TBI) from our standard dose of 10Gy (10, 8, 6, and 4Gy), in which rhesus CD34(+) cells were transduced with a VSVG-pseudotyped chimeric HIV-1 vector encoding enhanced green fluorescent protein (GFP) (or enhanced yellow fluorescent protein (YFP)). At similar to 6 months after transplantation, higher-dose TBI resulted in higher gene marking with logarithmic regression in peripheral blood cells. We then evaluated immunological tolerance for gene-modified cells, and found that lower-dose TBI allowed vigorous anti-GFP antibody production with logarithmic regression, while no significant anti-VSVG antibody formation was observed among all TBI groups. These data suggest that higher-dose TBI improves both engraftment and immunological tolerance for gene-modified cells. Additional immunosuppression might be required in RIC to induce tolerance for transgene products. Our findings should be valuable for developing conditioning regimens for HSC gene therapy applications. C1 [Uchida, Naoya; Weitzel, R. Patrick; Shvygin, Anna; Skala, Luke P.; Raines, Lydia; Tisdale, John F.] NIDDK, NHLBI, Mol & Clin Hematol Branch, NIH, Bethesda, MD 20892 USA. [Bonifacino, Aylin C.; Krouse, Allen E.; Metzger, Mark E.; Donahue, Robert E.] NHLBI, Hematol Branch, NIH, Bethesda, MD 20892 USA. RP Uchida, N (reprint author), NIDDK, NHLBI, Mol & Clin Hematol Branch, NIH, Bethesda, MD 20892 USA. EM uchidan@nhlbi.nih.gov FU Intramural Research Program of the National Heart, Lung, and Blood Institute; National Institute of Diabetes, Digestive, and Kidney Diseases at the National Institutes of Health FX This work was supported by the Intramural Research Program of the National Heart, Lung, and Blood Institute and the National Institute of Diabetes, Digestive, and Kidney Diseases at the National Institutes of Health. We thank Matthew Hsieh for editing out manuscript and the animal care and technical staff and veterinarians at 5 Research Court for their support. No competing financial interests exist. NR 22 TC 0 Z9 0 U1 0 U2 0 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 2329-0501 J9 MOL THER-METH CLIN D JI Mol.Ther.-Methods Clin. Dev. PY 2016 VL 3 AR UNSP 16059 DI 10.1038/mtm.2016.59 PG 6 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA EJ8DM UT WOS:000393455200050 PM 27652288 ER PT J AU Wang, GS Evans, CH Benson, JM Hutt, JA Seagrave, J Wilder, JA Grieger, JC Samulski, RJ Terse, PS AF Wang, Gensheng Evans, Christopher H. Benson, Janet M. Hutt, Julie A. Seagrave, JeanClare Wilder, Julie A. Grieger, Joshua C. Samulski, R. Jude Terse, Pramod S. TI Safety and biodistribution assessment of sc-rAAV2.5IL-1Ra administered via intra-articular injection in a mono-iodoacetate-induced osteoarthritis rat model SO MOLECULAR THERAPY-METHODS & CLINICAL DEVELOPMENT LA English DT Article ID INTERLEUKIN-1 RECEPTOR-ANTAGONIST; GENE-TRANSFER; ADENOASSOCIATED VIRUS; ARTICULAR-CARTILAGE; EXPRESSION; ARTHRITIS; SUPPRESSION; DELIVERY; THERAPY; JOINTS AB Interleukin-1 (IL-1) plays an important role in the pathophysiology of osteoarthritis (OA), and gene transfer of IL-1 receptor antagonist (IL-1Ra) holds promise for OA treatment. A preclinical safety and biodistribution study evaluated a self-complementary adeno-associated viral vector carrying rat IL-1Ra transgene (sc-rAAV2.5rIL-1Ra) at 5 x 10(8), 5 x 10(9), or 5 x 10(10) vg/knee, or human IL-1Ra transgene (sc-rAAV2.5hIL-1Ra) at 5 x 10(10) vg/knee, in Wistar rats with mono-iodoacetate (MIA)-induced OA at days 7, 26, 91, 180, and 364 following intra-articular injection. The MIA-induced OA lesions were consistent with the published data on this model. The vector genomes persisted in the injected knees for up to a year with only limited vector leakage to systemic circulation and uptake in tissues outside the knee. Low levels of IL-1Ra expression and mitigation of OA lesions were observed in the vector-injected knees, albeit inconsistently. Neutralizing antibodies against the vector capsid developed in a dose-dependent manner, but only the human vector induced a small splenic T-cell immune response to the vector capsid. No local or systemic toxicity attributable to vector administration was identified in the rats as indicated by clinical signs, body weight, feed consumption, clinical pathology, and gross and microscopic pathology through day 364. Taken together, the gene therapy vector demonstrated a favorable safety profile. C1 [Wang, Gensheng; Benson, Janet M.; Hutt, Julie A.; Seagrave, JeanClare; Wilder, Julie A.] Lovelace Resp Res Inst, Appl Toxicol & Gene Therapy Pharmacol Toxicol Pro, Albuquerque, NM 87108 USA. [Evans, Christopher H.] Mayo Clin, Rehabil Med Res Ctr, Rochester, MN USA. [Grieger, Joshua C.; Samulski, R. Jude] Univ N Carolina, Gene Therapy Ctr, Chapel Hill, NC USA. [Terse, Pramod S.] NIH, Natl Ctr Adv Translat Sci, Div Preclin Innovat, Bethesda, MD USA. RP Wang, GS (reprint author), Lovelace Resp Res Inst, Appl Toxicol & Gene Therapy Pharmacol Toxicol Pro, Albuquerque, NM 87108 USA. EM gwang@lrri.org FU NIAMS under BrIDGs/NCATS/NIH Program; NHLBI Gene Therapy Resource Program (GTRP) [HHSN268201200003I]; UNC Gene Therapy center FX This work was supported by NIAMS under BrIDGs/NCATS/NIH Program and NHLBI Gene Therapy Resource Program (GTRP) under Contract No. HHSN268201200003I to LRRI Pharm/Tox core. G.W. contributed to study design, data acquisition and interpretation, and manuscript draft, review, and approval; C.H.E. to study design, Mankin scoring data acquisition and interpretation, and manuscript review and approval; J.M.B. to study design, data acquisition and interpretation, and manuscript review and approval; J.A.H to pathology data acquisition and interpretation and manuscript review and approval; J.S. to study design, data acquisition and interpretation (particularly IL-1Ra expression), and manuscript review and approval; J.A.W. to ELISpot data acquisition and interpretation and manuscript review and approval; R.J.S to test and control article production and characterization and manuscript review and approval; and P.S.T. to study design, review of data acquisition and interpretation, and manuscript review and approval. Self-complementary AAV vector was produced at UNC vector core facility supported by UNC Gene Therapy center. All oversight on the production, validation, and QA/QC testing were carried out by Josh Grieger (UNC Gene Therapy Center). The authors thank the LRRI technical staff, especially Andrea Gomez, Glenna Jill Chavez, Genevieve Chavez, and Cecilia Rietz (for ELISpot analysis); Steven K. Seilkop, SKS Consulting Services, for his statistical analyses of the body weight and clinical pathology data; Steven C. Ghivizzani, University of Florida, for sharing the qPCR protocol; Declan Devine, Athlone Institute of Technology, for Mankin scoring; and Roberto Calcedo de Hoyo, University of Pennsylvania, for anti-AAV NAb analysis. NR 26 TC 1 Z9 1 U1 0 U2 1 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 2329-0501 J9 MOL THER-METH CLIN D JI Mol.Ther.-Methods Clin. Dev. PY 2016 VL 3 AR UNSP 15052 DI 10.1038/mtm.2015.52 PG 10 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA EJ8DM UT WOS:000393455200004 PM 26817025 ER PT J AU Steele, VR Maurer, JM Bernat, EM Calhoun, VD Kiehl, KA AF Steele, Vaughn R. Maurer, J. Michael Bernat, Edward M. Calhoun, Vince D. Kiehl, Kent A. TI Error-Related Processing in Adult Males With Elevated Psychopathic Traits SO PERSONALITY DISORDERS-THEORY RESEARCH AND TREATMENT LA English DT Article ID EVENT-RELATED POTENTIALS; GO/NOGO TASK; ANTERIOR CINGULATE; COGNITIVE CONTROL; BRAIN POTENTIALS; NEURAL SYSTEM; INDIVIDUALS; COMPONENTS; SCALE; ERN AB Psychopathy is a serious personality disorder characterized by dysfunctional affective and behavioral symptoms. In incarcerated populations, elevated psychopathic traits have been linked to increased rates of violent recidivism. Cognitive processes related to error processing have been shown to differentiate individuals with high and low psychopathic traits and may contribute to poor decision making that increases the risk of recidivism. Error processing abnormalities related to psychopathy may be attributable to error-monitoring (error detection) or posterror processing (error evaluation). A recent 'bottleneck' theory predicts deficiencies in posterror processing in individuals with high psychopathic traits. In the current study, incarcerated males (n = 93) performed a Go/NoGo response inhibition task while event-related potentials (ERPs) were recorded. Classic time-domain windowed component and principal component analyses were used to measure error-monitoring (as measured with the error-related negativity [ERN/Ne]) and posterror processing ( as measured with the error positivity [Pe]). Psychopathic traits were assessed using Hare's Psychopathy Checklist-Revised (PCL-R). PCL-R Total score, Factor 1 (interpersonal-affective traits), and Facet 3 (lifestyle traits) scores were positively related to posterror processes (i.e., increased Pe amplitude) but unrelated to error-monitoring processes (i.e., ERN/Ne). These results support the attentional bottleneck theory and further describe deficiencies related to elevated psychopathic traits that could be beneficial for new treatment strategies for psychopathy. C1 [Steele, Vaughn R.; Maurer, J. Michael; Calhoun, Vince D.; Kiehl, Kent A.] Mind Res Network, Albuquerque, NM USA. [Steele, Vaughn R.; Maurer, J. Michael; Calhoun, Vince D.; Kiehl, Kent A.] Lovelace Biomed & Environm Res Inst, Albuquerque, NM USA. [Maurer, J. Michael; Kiehl, Kent A.] Univ New Mexico, Dept Psychol, Albuquerque, NM 87131 USA. [Bernat, Edward M.] Univ Maryland, Dept Psychol, College Pk, MD 20742 USA. [Calhoun, Vince D.] Univ New Mexico, Dept Elect & Comp Engn, Albuquerque, NM 87131 USA. [Calhoun, Vince D.] Univ New Mexico, Dept Neurosci, Albuquerque, NM 87131 USA. [Calhoun, Vince D.] Univ New Mexico, Dept Comp Sci, Albuquerque, NM 87131 USA. RP Steele, VR (reprint author), NIDA, Intramural Res Program, NIH, 251 Bayview Blvd, Baltimore, MD 21224 USA. EM vaughn.r.steele@gmail.com FU National Institute of Mental Health [R01 MH070539-01] FX This research was supported National Institute of Mental Health Grant R01 MH070539-01 (PI: KAK). We are grateful of the staff and clients at New Mexico Correction Facilities in Grants, NM, and Santa Fe, NM for their support and making this research possible. NR 59 TC 1 Z9 1 U1 0 U2 1 PU EDUCATIONAL PUBLISHING FOUNDATION-AMERICAN PSYCHOLOGICAL ASSOC PI WASHINGTON PA 750 FIRST ST, NE, WASHINGTON, DC 20002-4242 USA SN 1949-2715 EI 1949-2723 J9 PERSONAL DISORD JI Personal. Disord. PD JAN PY 2016 VL 7 IS 1 BP 80 EP 90 DI 10.1037/per0000143 PG 11 WC Psychology, Clinical SC Psychology GA EL3GH UT WOS:000394507100010 PM 26479259 ER PT J AU Li, J You, XX Bian, C Yu, H Coon, SL Shi, Q AF Li, Jia You, Xinxin Bian, Chao Yu, Hui Coon, Steven L. Shi, Qiong TI Molecular Evolution of Aralkylamine N-Acetyltransferase in Fish: A Genomic Survey SO INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES LA English DT Article DE aralkylamine N-acetyltransferase; phylogenetic analysis; synteny; molecular evolution; Whole-Genome Duplication (WGD); gene loss ID MELATONIN; PINEAL; ZEBRAFISH; AANAT; EXPRESSION; DUPLICATION; DOPAMINE; GOLDFISH; RETINA; GENES AB All living organisms synchronize biological functions with environmental changes; melatonin plays a vital role in regulating daily and seasonal variations. Due to rhythmic activity of the timezyme aralkylamine N-acetyltransferase (AANAT), the blood level of melatonin increases at night and decreases during daytime. Whereas other vertebrates have a single form of AANAT, bony fishes possess various isoforms of aanat genes, though the reasons are still unclear. Here, we have taken advantage of multiple unpublished teleost aanat sequences to explore and expand our understanding of the molecular evolution of aanat in fish. Our results confirm that two rounds of whole-genome duplication (WGD) led to the existence of three fish isoforms of aanat, i.e., aanat1a, aanat1b, and aanat2; in addition, gene loss led to the absence of some forms from certain special fish species. Furthermore, we suggest the different roles of two aanat1s in amphibious mudskippers, and speculate that the loss of aanat1a, may be related to terrestrial vision change. Several important sites of AANAT proteins and regulatory elements of aanat genes were analyzed for structural comparison and functional forecasting, respectively, which provides insights into the molecular evolution of the differences between AANAT1 and AANAT2. C1 [Li, Jia; Yu, Hui; Shi, Qiong] Univ Chinese Acad Sci, BGI Educ Ctr, Shenzhen 518083, Peoples R China. [Li, Jia; You, Xinxin; Bian, Chao; Yu, Hui; Shi, Qiong] BGI, Guangdong Prov Key Lab Mol Breeding Marine Econ A, Shenzhen Key Lab Marine Genom, Shenzhen 518083, Peoples R China. [Bian, Chao; Shi, Qiong] BGI Zhenjiang Inst Hydrobiol, Zhenjiang 212000, Peoples R China. [Coon, Steven L.] NIH, Mol Genom Lab, Bldg 10, Bethesda, MD 20892 USA. RP Shi, Q (reprint author), Univ Chinese Acad Sci, BGI Educ Ctr, Shenzhen 518083, Peoples R China.; Shi, Q (reprint author), BGI, Guangdong Prov Key Lab Mol Breeding Marine Econ A, Shenzhen Key Lab Marine Genom, Shenzhen 518083, Peoples R China.; Shi, Q (reprint author), BGI Zhenjiang Inst Hydrobiol, Zhenjiang 212000, Peoples R China.; Coon, SL (reprint author), NIH, Mol Genom Lab, Bldg 10, Bethesda, MD 20892 USA. EM lijia1@genomics.cn; youxinxin@genomics.cn; bianchao@genomics.cn; yuhui@genomics.cn; coons@mail.nih.gov; shiqiong@genomics.cn FU China 863 Project [2012AA10A407]; Special Project on the Integration of Industry, Education and Research of Guangdong Province [2013B090800017]; Shenzhen Special Program for Future Industrial Development [JSGG20141020113728803]; Shenzhen Dapeng Special Program for Industrial Development [QT20140101]; Shenzhen Scientific R D Grant [CXB201108250095A]; Intramural Research Program of the Eunice Kennedy Shriver National Institute of Child Health and Human Development at the National Institutes of Health, Bethesda, MD, USA FX The work was supported by China 863 Project (No. 2012AA10A407), Special Project on the Integration of Industry, Education and Research of Guangdong Province (No. 2013B090800017), Shenzhen Special Program for Future Industrial Development (No. JSGG20141020113728803), Shenzhen Dapeng Special Program for Industrial Development (No. QT20140101), Shenzhen Scientific R & D Grant (No. CXB201108250095A), and the Intramural Research Program of the Eunice Kennedy Shriver National Institute of Child Health and Human Development at the National Institutes of Health, Bethesda, MD, USA. NR 49 TC 2 Z9 2 U1 0 U2 0 PU MDPI AG PI BASEL PA ST ALBAN-ANLAGE 66, CH-4052 BASEL, SWITZERLAND SN 1422-0067 J9 INT J MOL SCI JI Int. J. Mol. Sci. PD JAN PY 2016 VL 17 IS 1 AR 51 DI 10.3390/ijms17010051 PG 15 WC Biochemistry & Molecular Biology; Chemistry, Multidisciplinary SC Biochemistry & Molecular Biology; Chemistry GA DK0DW UT WOS:000374583800049 ER PT J AU Nishiura, H Endo, A Saitoh, M Kinoshita, R Ueno, R Nakaoka, S Miyamatsu, Y Dong, YP Chowell, G Mizumoto, K AF Nishiura, Hiroshi Endo, Akira Saitoh, Masaya Kinoshita, Ryo Ueno, Ryo Nakaoka, Shinji Miyamatsu, Yuichiro Dong, Yueping Chowell, Gerardo Mizumoto, Kenji TI Identifying determinants of heterogeneous transmission dynamics of the Middle East respiratory syndrome (MERS) outbreak in the Republic of Korea, 2015: a retrospective epidemiological analysis SO BMJ OPEN LA English DT Article ID HONG-KONG; TIME; RISK; SARS; SPREAD; DEATH; COV AB Objectives: To investigate the heterogeneous transmission patterns of Middle East respiratory syndrome (MERS) in the Republic of Korea, with a particular focus on epidemiological characteristics of superspreaders. Design: Retrospective epidemiological analysis. Setting: Multiple healthcare facilities of secondary and tertiary care centres in an urban setting. Participants: A total of 185 laboratory-confirmed cases with partially known dates of illness onset and most likely sources of infection. Primary and secondary outcome measures: Superspreaders were identified using the transmission tree. The reproduction number, that is, the average number of secondary cases produced by a single primary case, was estimated as a function of time and according to different types of hosts. Results: A total of five superspreaders were identified. The reproduction number throughout the course of the outbreak was estimated at 1.0 due to reconstruction of the transmission tree, while the variance of secondary cases generated by a primary case was 52.1. All of the superspreaders involved in this outbreak appeared to have generated a substantial number of contacts in multiple healthcare facilities (association: p<0.01), generating on average 4.0 (0.0-8.6) and 28.6 (0.0-63.9) secondary cases among patients who visited multiple healthcare facilities and others. The time-dependent reproduction numbers declined substantially below the value of 1 on and after 13 June 2015. Conclusions: Superspreaders who visited multiple facilities drove the epidemic by generating a disproportionate number of secondary cases. Our findings underscore the need to limit the contacts in healthcare settings. Contact tracing efforts could assist early laboratory testing and diagnosis of suspected cases. C1 [Nishiura, Hiroshi; Endo, Akira; Saitoh, Masaya; Kinoshita, Ryo; Ueno, Ryo; Nakaoka, Shinji; Miyamatsu, Yuichiro; Dong, Yueping] Univ Tokyo, Grad Sch Med, Infect Dis Epidemiol Team, Tokyo, Japan. [Nishiura, Hiroshi; Saitoh, Masaya; Kinoshita, Ryo; Nakaoka, Shinji; Miyamatsu, Yuichiro; Dong, Yueping; Mizumoto, Kenji] Japan Sci & Technol Agcy, CREST, Saitama, Japan. [Nishiura, Hiroshi; Kinoshita, Ryo; Miyamatsu, Yuichiro; Mizumoto, Kenji] Hokkaido Univ, Grad Sch Med, Sapporo, Hokkaido, Japan. [Saitoh, Masaya] Inst Stat Math, Tokyo, Japan. [Chowell, Gerardo] Georgia State Univ, Sch Publ Hlth, Atlanta, GA 30303 USA. [Chowell, Gerardo] NIH, Div Int Epidemiol & Populat Studies, Fogarty Int Ctr, Bldg 10, Bethesda, MD 20892 USA. [Mizumoto, Kenji] Univ Tokyo, Grad Sch Arts & Sci, Tokyo, Japan. RP Nishiura, H (reprint author), Univ Tokyo, Grad Sch Med, Infect Dis Epidemiol Team, Tokyo, Japan.; Nishiura, H (reprint author), Japan Sci & Technol Agcy, CREST, Saitama, Japan.; Nishiura, H (reprint author), Hokkaido Univ, Grad Sch Med, Sapporo, Hokkaido, Japan. EM nishiurah@gmail.com OI Nishiura, Hiroshi/0000-0003-0941-8537 FU JSPS KAKENHI [26670308, 26700028]; Japan Agency for Medical Research and Development; Japan Science and Technology Agency (JST) CREST programme; RISTEX programme for Science, of the Science, Technology and Innovation Policy; Division of International Epidemiology and Population Studies, The Fogarty International Center, US National Institutes of Health - Office of Pandemics and Emerging Threats at the US Department of Health and Human Services; NSF [1414374]; UK Biotechnology and Biological Sciences Research Council [BB/M008894/1]; NSF-IIS [1518939] FX HN received funding support from the JSPS KAKENHI Grant, numbers 26670308 and 26700028, Japan Agency for Medical Research and Development, the Japan Science and Technology Agency (JST) CREST programme and RISTEX programme for Science, of the Science, Technology and Innovation Policy. GC acknowledges financial support from the Division of International Epidemiology and Population Studies, The Fogarty International Center, US National Institutes of Health, funded in part by the Office of Pandemics and Emerging Threats at the US Department of Health and Human Services, as well as support from NSF Grant number 1414374, as part of the joint NSF-NIH-USDA Ecology and Evolution of Infectious Diseases programme, UK Biotechnology and Biological Sciences Research Council Grant number BB/M008894/1 and NSF-IIS Grant number 1518939. The funders had no role in study design, data collection and analysis, decision to publish, nor in preparation of the manuscript. NR 32 TC 6 Z9 6 U1 0 U2 0 PU BMJ PUBLISHING GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 2044-6055 J9 BMJ OPEN JI BMJ Open PY 2016 VL 6 IS 2 AR e009936 DI 10.1136/bmjopen-2015-009936 PG 10 WC Medicine, General & Internal SC General & Internal Medicine GA DT5HX UT WOS:000381514500077 PM 26908522 ER PT S AU Liang, ZH Powell, A Ersoy, I Poostchi, M Silamut, K Palaniappan, K Guo, P Hossain, MA Sameer, A Maude, RJ Huang, JX Jaeger, S Thoma, G AF Liang, Zhaohui Powell, Andrew Ersoy, Ilker Poostchi, Mahdieh Silamut, Kamolrat Palaniappan, Kannappan Guo, Peng Hossain, Md Amir Sameer, Antani Maude, Richard James Huang, Jimmy Xiangji Jaeger, Stefan Thoma, George BE Tian, T Jiang, Q Liu, Y Burrage, K Song, J Wang, Y Hu, X Morishita, S Zhu, Q Wang, G TI CNN-Based Image Analysis for Malaria Diagnosis SO 2016 IEEE INTERNATIONAL CONFERENCE ON BIOINFORMATICS AND BIOMEDICINE (BIBM) SE IEEE International Conference on Bioinformatics and Biomedicine-BIBM LA English DT Proceedings Paper CT IEEE International Conference on Bioinformatics and Biomedicine (IEEE BIBM) CY DEC 15-18, 2016 CL Shenzhen, PEOPLES R CHINA SP IEEE, IEEE Comp Soc, Natl Sci Fdn, Harbin Inst Technol DE convolutional neural network; deep learning; malaria; computer-aided diagnosis; machine learning ID ERYTHROCYTES; RECOGNITION AB Malaria is a major global health threat. The standard way of diagnosing malaria is by visually examining blood smears for parasite-infected red blood cells under the microscope by qualified technicians. This method is inefficient and the diagnosis depends on the experience and the knowledge of the person doing the examination. Automatic image recognition technologies based on machine learning have been applied to malaria blood smears for diagnosis before. However, the practical performance has not been sufficient so far. This study proposes a new and robust machine learning model based on a convolutional neural network (CNN) to automatically classify single cells in thin blood smears on standard microscope slides as either infected or uninfected. In a ten-fold cross-validation based on 27,578 single cell images, the average accuracy of our new 16-layer CNN model is 97.37%. A transfer learning model only achieves 91.99% on the same images. The CNN model shows superiority over the transfer learning model in all performance indicators such as sensitivity (96.99% vs 89.00%), specificity (97.75% vs 94.98%), precision (97.73% vs 95.12%), F1 score (97.36% vs 90.24%), and Matthews correlation coefficient (94.75% vs 85.25%). C1 [Liang, Zhaohui; Huang, Jimmy Xiangji] York Univ, Sch Informat Technol, Toronto, ON M3J 1P3, Canada. [Powell, Andrew] Swarthmore Coll, Dept Comp Sci, Swarthmore, PA 19081 USA. [Ersoy, Ilker] Univ Missouri, Sch Med, Columbia, MO 65212 USA. [Poostchi, Mahdieh; Palaniappan, Kannappan] Univ Missouri, Dept Comp Sci, Columbia, MO 65211 USA. [Silamut, Kamolrat; Maude, Richard James] Mahidol Univ, Mahidol Oxford Trop Med Res Unit, Bangkok, Thailand. [Guo, Peng] Missouri S&T, Dept Elect & Comp Engn, Rolla, MO 65409 USA. [Hossain, Md Amir] Chittagong Med Coll Hosp, Chittagong, Bangladesh. [Sameer, Antani; Jaeger, Stefan; Thoma, George] NIH, Natl Lib Med, Bethesda, MD 20894 USA. RP Jaeger, S (reprint author), NIH, Natl Lib Med, Bethesda, MD 20894 USA. EM stefan.jaeger@nih.gov FU Wellcome Trust of Great Britain; NSERC CREATE award; ORF-RE award in BRAIN Alliance of Canada; National Natural Science Foundation of China [81573827] FX We would like to acknowledge all the patients in Bangladesh. Mahidol-Oxford Tropical Medicine Research Unit is funded by the Wellcome Trust of Great Britain. Other support includes the NSERC CREATE award, the ORF-RE award in BRAIN Alliance of Canada, and the National Natural Science Foundation of China (No. 81573827). NR 24 TC 0 Z9 0 U1 3 U2 3 PU IEEE COMPUTER SOC PI LOS ALAMITOS PA 10662 LOS VAQUEROS CIRCLE, PO BOX 3014, LOS ALAMITOS, CA 90720-1264 USA SN 2156-1125 BN 978-1-5090-1610-5 J9 IEEE INT C BIOINFORM PY 2016 BP 493 EP 496 PG 4 WC Computer Science, Interdisciplinary Applications; Medical Informatics SC Computer Science; Medical Informatics GA BG9GY UT WOS:000393191700082 ER PT S AU Liu, CL Xiao, LM Xu, R Gao, P Samuel, K Brazhnik, O AF Liu, Chunlei Xiao, Lemin Xu, Roger Gao, Pan Samuel, Ken Brazhnik, Olga BE Tian, T Jiang, Q Liu, Y Burrage, K Song, J Wang, Y Hu, X Morishita, S Zhu, Q Wang, G TI Multidimensional Visual Tool for Analysis of a Complex Program in Clinical & Translational Research SO 2016 IEEE INTERNATIONAL CONFERENCE ON BIOINFORMATICS AND BIOMEDICINE (BIBM) SE IEEE International Conference on Bioinformatics and Biomedicine-BIBM LA English DT Proceedings Paper CT IEEE International Conference on Bioinformatics and Biomedicine (IEEE BIBM) CY DEC 15-18, 2016 CL Shenzhen, PEOPLES R CHINA SP IEEE, IEEE Comp Soc, Natl Sci Fdn, Harbin Inst Technol DE CTSA; translational sciences; visual analytics; data collection; data processing; data visualization; D3 visualization AB The National Institutes of Health's (NIH) Clinical and Translational Science Award (CTSA) program is NIH's largest single investment in clinical research, and it is one of the world's largest programs in clinical and translational sciences [1]. To help stakeholders better understand, investigate, and utilize the CTSA program, we have developed an automatic and multidimensional visual analytical tool, which enables them to collect open source data as well as store, process, query, share, and visualize the data. The resulting tool is the software implementation of research we have performed during a two-year SBm Phase II project. In this paper we introduce the design and features of this software and demonstrate its functionalities through use cases. C1 [Liu, Chunlei; Xiao, Lemin; Xu, Roger; Gao, Pan; Samuel, Ken] Intelligent Automation Inc, Rockville, MD 20855 USA. [Brazhnik, Olga] Natl Inst Hlth, Natl Ctr Adv Translat Sci, Bethesda, MD USA. RP Liu, CL (reprint author), Intelligent Automation Inc, Rockville, MD 20855 USA. EM cliu@i-a-i.com; lxiao.fn@i-a-i.com; hgxu@i-a-i.com; pgao@i-a-i.com; ksamuel@i-a-i.com; brazhnik@mail.nih.gov FU National Center for Advancing Translational Sciences at the National Institutes of Health [HHSN271201400050C] FX This study is supported by contract HHSN271201400050C from the National Center for Advancing Translational Sciences at the National Institutes of Health. NR 3 TC 0 Z9 0 U1 0 U2 0 PU IEEE COMPUTER SOC PI LOS ALAMITOS PA 10662 LOS VAQUEROS CIRCLE, PO BOX 3014, LOS ALAMITOS, CA 90720-1264 USA SN 2156-1125 BN 978-1-5090-1610-5 J9 IEEE INT C BIOINFORM PY 2016 BP 1194 EP 1200 PG 7 WC Computer Science, Interdisciplinary Applications; Medical Informatics SC Computer Science; Medical Informatics GA BG9GY UT WOS:000393191700204 ER PT S AU Liu, CL Xiao, LM Xu, R Brazhnik, O AF Liu, Chunlei Xiao, Lemin Xu, Roger Brazhnik, Olga BE Tian, T Jiang, Q Liu, Y Burrage, K Song, J Wang, Y Hu, X Morishita, S Zhu, Q Wang, G TI Assessing the Public Image of the NIH Clinical and Translational Science Awards (CTSA) Program through Analysis of Publications SO 2016 IEEE INTERNATIONAL CONFERENCE ON BIOINFORMATICS AND BIOMEDICINE (BIBM) SE IEEE International Conference on Bioinformatics and Biomedicine-BIBM LA English DT Proceedings Paper CT IEEE International Conference on Bioinformatics and Biomedicine (IEEE BIBM) CY DEC 15-18, 2016 CL Shenzhen, PEOPLES R CHINA SP IEEE, IEEE Comp Soc, Natl Sci Fdn, Harbin Inst Technol DE CTSA; systematic data retrieval; data analytics; research topic extraction; collaboration study AB NIH's Clinical and Translational Science Award (CTSA) program represents the National Institutes of Health (NIH) largest single investment in clinical research, as well as one of the world's largest programs in clinical and translational sciences [1]. Although there exist multiple databases and tools to assist NIH program staffs in assessing the program, this work is focused on exploring the image of the program from publically available data sources. In this study, we address both the limitation of linking multiple data elements including CTSA awards and published scientific work, and the challenge of applying advanced data analytic methods to quantitatively evaluate complex NIH programs, considering the CTSA program as an example. We studied multiple dimensions of publications including time, journal, institute and funding; extracted prevailing research topics and productive researchers supported by the program; applied graph analytics to study collaborations of the CTSA program with other funding agencies, and collaborations within the CTSA program. C1 [Liu, Chunlei; Xiao, Lemin; Xu, Roger] Intelligent Automation Inc, Rockville, MD 20855 USA. [Brazhnik, Olga] Natl Inst Hlth, Natl Ctr Adv Translat Sci, Bethesda, MD USA. RP Liu, CL (reprint author), Intelligent Automation Inc, Rockville, MD 20855 USA. EM cliu@i-a-i.com; lxiao.fn@i-a-i.com; hgxu@i-a-i.com; brazhnik@mail.nih.gov FU National Center for Advancing Translational Sciences at National Institutes of Health [HHSN271201400050C] FX This study is supported by contract HHSN271201400050C from the National Center for Advancing Translational Sciences at National Institutes of Health. NR 8 TC 0 Z9 0 U1 0 U2 0 PU IEEE COMPUTER SOC PI LOS ALAMITOS PA 10662 LOS VAQUEROS CIRCLE, PO BOX 3014, LOS ALAMITOS, CA 90720-1264 USA SN 2156-1125 BN 978-1-5090-1610-5 J9 IEEE INT C BIOINFORM PY 2016 BP 1207 EP 1213 PG 7 WC Computer Science, Interdisciplinary Applications; Medical Informatics SC Computer Science; Medical Informatics GA BG9GY UT WOS:000393191700206 ER PT J AU Lee, JJ Vattikuti, S Chow, CC AF Lee, James J. Vattikuti, Shashaank Chow, Carson C. TI Uncovering the Genetic Architectures of Quantitative Traits SO COMPUTATIONAL AND STRUCTURAL BIOTECHNOLOGY JOURNAL LA English DT Review DE Statistical genetics; Quantitative genetics; Population genetics; Average effect of gene substitution; Heritability; GWAS; Compressed sensing; Review ID GENOME-WIDE-ASSOCIATION; BODY-MASS INDEX; HUMAN HEIGHT; HERITABILITY ESTIMATION; MISSING HERITABILITY; AVERAGE EXCESS; COMPLEX TRAIT; COMMON SNPS; VARIANTS; PROPORTION AB The aim of a genome-wide association study (GWAS) is to identify loci in the human genome affecting a phenotype of interest. This review summarizes some recent work on conceptual and methodological aspects of GWAS. The average effect of gene substitution at a given causal site in the genome is the key estimand in GWAS, and we argue for its fundamental importance. Implicit in the definition of average effect is a linear model relating genotype to phenotype. The fraction of the phenotypic variance ascribable to polymorphic sites with nonzero average effects in this linear model is called the heritability, and we describe methods for estimating this quantity from GWAS data. Finally, we show that the theory of compressed sensing can be used to provide a sharp estimate of the sample size required to identify essentially all sites contributing to the heritability of a given phenotype. Published by Elsevier B.V. on behalf of the Research Network of Computational and Structural Biotechnology. C1 [Lee, James J.] Univ Minnesota Twin Cities, Dept Psychol, Minneapolis, MN 55455 USA. [Vattikuti, Shashaank; Chow, Carson C.] NIDDK, Math Biol Sect, LBM, NIH, Bethesda, MD 20892 USA. RP Lee, JJ (reprint author), Univ Minnesota Twin Cities, Dept Psychol, Minneapolis, MN 55455 USA.; Vattikuti, S; Chow, CC (reprint author), NIDDK, Math Biol Sect, LBM, NIH, Bethesda, MD 20892 USA. EM leex2293@umn.edu; vattikutis@niddk.nih.gov; carsonc@niddk.nih.gov OI Lee, James J/0000-0001-6547-5128 NR 65 TC 1 Z9 1 U1 2 U2 2 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 2001-0370 J9 COMPUT STRUCT BIOTEC JI Comp. Struct. Biotechnol. J.. PY 2016 VL 14 BP 28 EP 34 DI 10.1016/j.csbj.2015.10.002 PG 7 WC Biotechnology & Applied Microbiology SC Biotechnology & Applied Microbiology GA EI6TO UT WOS:000392630000005 PM 27076877 ER PT J AU Livingston, CA Fabre, KM Tagle, DA AF Livingston, Christine A. Fabre, Kristin M. Tagle, Danilo A. TI Facilitating the commercialization and use of organ platforms generated by the microphysiological systems (Tissue Chip) program through public-private partnerships SO COMPUTATIONAL AND STRUCTURAL BIOTECHNOLOGY JOURNAL LA English DT Article DE Tissue Chip; Commercialization; Microphysiological systems; Organs-on-chips; Public-private partnerships; RFI: Request for information ID ON-CHIPS; DRUG DISCOVERY AB Microphysiological systems (organs-on-chips, tissue chips) are devices designed to recapitulate human physiology that could be used to better understand drug responses not easily addressed using other in vivo systems or in vitro animal models. Although still in development, initial results seem promising as tissue chips exhibit in vivo systems-like functional responses. The National Center for Advancing Translation Science (NCATS) identifies this technology as a potential tool that could improve the process of getting safer, more effective treatments to patients, and has led to the Tissue Chip Program, which aims to develop, integrate and validate major organ systems for testing. In addition to organ chip development, NCATS emphasizes disseminating the technology to researchers. Commercialization has become an important issue, reflecting the difficulty of translation from discovery to adoption and wide availability. Therefore, NCATS issued a Request for Information (RFI) targeted to existing partnerships for commercializing tissue chips. The goal was to identify successes, failures and the best practices that could provide useful guidance for future partnerships aiming to make tissue chip technology widely available. (C) 2016 Livingston et al.. Published by Elsevier B.V. on behalf of the Research Network of Computational and Structural Biotechnology. C1 [Livingston, Christine A.; Fabre, Kristin M.; Tagle, Danilo A.] NIH, Natl Ctr Adv Translat Sci, Bethesda, MD 20892 USA. RP Tagle, DA (reprint author), NIH, Natl Ctr Adv Translat Sci, Bethesda, MD 20892 USA. NR 22 TC 0 Z9 0 U1 1 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 2001-0370 J9 COMPUT STRUCT BIOTEC JI Comp. Struct. Biotechnol. J.. PY 2016 VL 14 BP 207 EP 210 DI 10.1016/j.csbj.2016.04.003 PG 4 WC Biotechnology & Applied Microbiology SC Biotechnology & Applied Microbiology GA EI6TO UT WOS:000392630000025 PM 27904714 ER PT J AU Lu, C O'Connor, GT Dupuis, J Kolaczyk, ED AF Lu, Chen O'Connor, George T. Dupuis, Josee Kolaczyk, Eric D. TI Meta-Analysis for Penalized Regression Methods with Multi-Cohort Genome-Wide Association Studies SO HUMAN HEREDITY LA English DT Article DE Meta-analysis; Multi-cohorts; Penalized regression; Data splitting ID VARIABLE SELECTION; ORACLE PROPERTIES; LASSO AB Objective: Penalized regression has been successfully applied in genome-wide association studies. While meta-analysis is often conducted to increase power and protect patients' confidentiality, methods for meta-analyzing results of penalized regression in multi-cohort setting are still under development. Methods: We propose to use a data-splitting method to obtain valid p values (or equivalently, coefficient estimates and standard errors) for meta-analysis across multiple cohorts. We examine two ways of splitting data in multicohort setting and propose three methods to conduct metaanalysis based on p values. We compare the three metaanalysis methods to mega-analysis, which consists of pooling individual level data. We also apply our proposed meta-analysis approaches to the Framingham Heart Study data, where we divide the original dataset into four parts to create a multi-cohort scenario. Results: The simulations suggest that splitting cohorts has better performance than splitting data within each cohort. The real data application also shows that this method provides results that are similar to the mega-analysis. Conclusion: After comparing the three methods that we proposed to conduct meta-analysis, we recommend splitting cohorts rather than datasets to obtain valid p values for meta-analysis of results from penalized regression in multi-cohort setting. (C) 2016 S. Karger AG, Basel C1 [Lu, Chen; Dupuis, Josee] Boston Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02118 USA. [O'Connor, George T.] Boston Univ, Sch Med, Dept Med, Ctr Pulm, Boston, MA 02118 USA. [O'Connor, George T.; Dupuis, Josee] NHLBI, Framingham Heart Study, Framingham, MA USA. [Dupuis, Josee; Kolaczyk, Eric D.] Boston Univ, Program Bioinformat, Boston, MA 02118 USA. [Kolaczyk, Eric D.] Boston Univ, Dept Math & Stat, Boston, MA 02118 USA. RP Lu, C (reprint author), Boston Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02118 USA. EM chenlu@bu.edu FU National Institute Health [DK078616, ES020827, GM078987, AG028321, N01 HC25195, P01 AI050516] FX This work was supported in part by National Institute Health grants DK078616, ES020827, GM078987, AG028321, N01 HC25195 and P01 AI050516. This research was conducted using the Linux Clusters for Genetic Analysis (LinGA) computing resources at Boston University Medical Campus. NR 23 TC 0 Z9 0 U1 1 U2 1 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 0001-5652 EI 1423-0062 J9 HUM HERED JI Hum. Hered. PY 2016 VL 81 IS 3 BP 142 EP 149 DI 10.1159/000447969 PG 8 WC Genetics & Heredity SC Genetics & Heredity GA EJ2RW UT WOS:000393059800002 PM 28002817 ER PT J AU Xu, NZ Linnoila, RI Kimura, S AF Xu Naizhen Linnoila, R. Ilona Kimura, Shioko TI Co-expression of Achaete-Scute Homologue-1 and Calcitonin Gene-Related Peptide during NNK-Induced Pulmonary Neuroendocrine Hyperplasia and Carcinogenesis in Hamsters SO JOURNAL OF CANCER LA English DT Article DE lung; ASCL1; CGRP; neuroendocrine hyperplasia; NNK ID EPITHELIAL-CELLS; MESSENGER-RNA; LUNG CANCERS; TUMORS; DIFFERENTIATION; PROLIFERATION; MICE; 4-(METHYLNITROSAMINO)-1-(3-PYRIDYL)-1-BUTANONE; TUMORIGENESIS; EXPRESSION AB Achaete-scute homologue-1 or ASCL1 (MASH1, hASH1) plays roles in neural development and pulmonary neuroendocrine (NE) differentiation, and it is expressed in certain lung cancers. This study was aimed to assess whether and/or how ASCL1 plays a role in 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK)-induced pulmonary NE hyperplasia and carcinogenesis in hamsters. Hamsters were injected 3 times weekly with either NNK or solvent alone (control) for treatment periods of 6 and 24 weeks, both without and with 6-week recovery. Immunohistochemical analysis was carried out to examine the expressions of ASCL1, CGRP (calcitonin gene-related peptide), secretoglobin SCGB1A1 (club [Clara] cell specific 10 kD protein, CC10, CCSP), synaptophysin (SYP), and PCNA (proliferating cell nuclear antigen). The number of ASCL1-expressing NE foci per airway increased from 0.8 in controls to 1.6 and 2.0 during NNK exposure for 6 and 24 weeks, respectively, and the number of cells per foci doubled after NNK exposure. Most ASCL1-expressing cells in NEBs (neuroepithelial bodies) were also CGRP immunoreactive; NNK enhanced this co-expression with CGRP, a NE marker with known proliferation-promoting properties. NNK also increased PCNA expression within NE foci. NNK-induced tumors showed no immunoreactivity for NE markers. This study confirms ASCL1 as an excellent marker for pulmonary NE cells and demonstrates CGRP co-expression in ASCL1-positive NEB cells participating in NNK-induced NE hyperplasia. C1 [Xu Naizhen; Linnoila, R. Ilona] NCI, Cell & Canc Biol Branch, NIH, Bethesda, MD 20892 USA. [Kimura, Shioko] NCI, Lab Metab, NIH, Bethesda, MD 20892 USA. RP Kimura, S (reprint author), NIH, Bldg 37,Rm 3106, Bethesda, MD 20892 USA. EM kimuras@mail.nih.gov FU Intramural Research Program of the National Cancer Institute, Center for Cancer Research [ZIA SC000167, ZIA BC010449] FX This work was supported by an Intramural Research Program of the National Cancer Institute, Center for Cancer Research (ZIA SC000167 for RIL and ZIA BC010449 for SK). We gratefully acknowledge Dr. Hanspeter Witschi (Institute of Toxicology and Environmental Health, University of California, Davis, CA) for providing the NNK hamster model, and we thank Dr. Franco J. DeMayo for SCGB1A1 antibody. NR 35 TC 0 Z9 0 U1 0 U2 0 PU IVYSPRING INT PUBL PI LAKE HAVEN PA PO BOX 4546, LAKE HAVEN, NSW 2263, AUSTRALIA SN 1837-9664 J9 J CANCER JI J. Cancer PY 2016 VL 7 IS 14 BP 2124 EP 2131 DI 10.7150/jca.16399 PG 8 WC Oncology SC Oncology GA EJ2YZ UT WOS:000393078800023 ER PT J AU Vorobyova, DA Lebedeva, AM Vagida, MS Ivanova, OI Felker, EI Gontarenko, VN Shpektor, AV Margolis, LB Vasilieva, EY AF Vorobyova, D. A. Lebedeva, A. M. Vagida, M. S. Ivanova, O. I. Felker, E. I. Gontarenko, V. N. Shpektor, A. V. Margolis, L. B. Vasilieva, E. Yu TI Immunological Analysis of Human Atherosclerotic Plaques in ex vivo Culture System SO KARDIOLOGIYA LA Russian DT Article DE atherosclerotic plaque; atherosclerosis; immunity; lymphocytes; tissue culture ID SMOOTH-MUSCLE CELLS; E-/-MICE; T-CELLS; ENDOTHELIAL-CELLS; DEFICIENT MICE; ANIMAL-MODELS; LESIONS; ATHEROGENESIS; LYMPHOCYTES AB The aim of the study: to analyze the dynamics of lymphocytic composition of human atherosclerotic plaques in ex vivo culture system. Materials and methods. The study included 15 atherosclerotic plaques obtained from patients who underwent carotid endarterectomy. Plaques were cultured as ring-shaped explants on collagen rafts in culture medium of special composition in CO2 incubator according to the previously developed technique. On day 0, and also on the 4th and 19th days of culture we extracted cells from plaque explants and analyzed B- and T-lymphocytic content of the tissue, as well as the percentage of CD16(+) natural killer (NK) cells, using multichromatic flow cytometry. For this purpose we digested the explants with an original enzymatic cocktail, which allows preservation of cell surface markers, and we stained extracted cells with fluorescence-labelled monoclonal antibodies against CD45, CD3, CD19, CD4, CD8, CD16. In addition, we estimated the amount of interleukin 2 (IL-2) and interferon-gamma (IFN-gamma)-producing T-cells by means of flow cytometry. Results. After 4 days of culture the amount of lymphocytes in plaques' explants decreased, however live lymphocytes were still preserved (2619.3 [1680.4, 3478.2] cells/100mg tissue). Viable lymphocytes' population included T cells (2123.4 [484.9; 3181.2] cells/100 mg tissue), B cells (5.6 [3.4, 27.9] cell/100 mg tissue) and CD16(+) NK cells (10.6 [1.8, 23.7] cells/100mg tissue). On the 4th day of culture T cells were presented by CD4(+)CD8(-) (797 [475.5, 1000.7] cells/100mg tissue, 37.5 [32.1; 46.3]%) and CD4(-)CD8(+) (686.2 [423.6; 1158.4] cells/100 mg tissue, 45.6 [38.1; 47.9]%) populations. The percentage of CD4(+)CD8(-) T cell population decreased compared to the 1st day of culture, and this decrease correlated with the increase in CD4-CD8- T cells' content (p < 0.05). Additionally, after 4 days of culture we found in tissue explants both CD8(+) (17.5[13.3;19.9]%) and CD8(-) (9.9 [6.4; 14]%) IFN-gamma-producing T-cells, however, their percentage, as well as the percentage of IL-2-producing T cells tended to decrease. After 19 days of culture explants of atherosclerotic plaques also contained lymphocytes (2830.1 [2350.3, 5900.2] cells/100mg tissue). Lymphocytes' population included T cells (2594.5 [2035.7, 5306.7] cells/100mg tissue), presented by CD4(+)CD8(-) (1016.8 [671.2, 2201.7] cells/100mg tissue, 42.3 [34.3; 47.8]%) and CD4(-)CD8(+) (1534.3 [813.8; 2207.2] cells/100mg tissue, 50.8 [45.6; 56.5]%) subsets, B cells (31 [18.3; 64.4] cell/100 mg tissue) and CD16(+) NK cells (44.9 [33.4; 138.9] cells/100 mg of tissue). Discussion. An ex vivo model of human atherosclerotic plaque culture that we previously developed enables to preserve viability of various lymphocyte subsets for up to 19 days. We also found that cultured tissue explants retain T cells that can maintain T-helper-1-dependent immune response, which demonstrates inflammation in atherosclerotic plaques. Our results allow to perform experiments on immunological mechanisms of atherogenesis and to develop new approaches for treatment of atherosclerosis, devoted to the suppression of local inflammatory processes in atherosclerotic plaques. Conclusions. An ex vivo model of human atherosclerotic plaque preserves CD4(+)CD8(-) and CD4(-)CD8(+) T cells, B cells, and CD16(+) NK cells for a long time. Moreover, after 4 days of culture tissue explants also retain IFN-gamma(+) + T cells. C1 [Vorobyova, D. A.; Lebedeva, A. M.; Vagida, M. S.; Ivanova, O. I.; Felker, E. I.; Shpektor, A. V.; Vasilieva, E. Yu] AI Evdokimov Moscow State Univ Med & Dent, Lab Atherothrombosis, Moscow, Russia. [Gontarenko, V. N.] AV Vishnevsky Inst Surg, Dept Vasc Surg, Moscow, Russia. [Margolis, L. B.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Sect Intercellular Interact, NIH, Bethesda, MD USA. RP Lebedeva, AM (reprint author), AI Evdokimov Moscow State Univ Med & Dent, Lab Atherothrombosis, Moscow, Russia. EM asya.lebedev@mail.ru NR 29 TC 0 Z9 0 U1 0 U2 0 PU IZDATELSTVO MEDITSINA PI MOSCOW PA PETROVERIGSKII PER 6-8, K-142 MOSCOW, RUSSIA SN 0022-9040 J9 KARDIOLOGIYA JI Kardiologiya PY 2016 VL 56 IS 11 BP 78 EP 85 DI 10.18565/cardio.2016.11.78-85 PG 8 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA EJ5LQ UT WOS:000393259900011 PM 28290822 ER PT J AU Ehsani, JP Ionides, E Klauer, SG Perlus, JG Gee, BT AF Ehsani, Johnathon P. Ionides, Edward Klauer, Sheila G. Perlus, Jessamyn G. Gee, Benjamin T. TI Effectiveness of Cell Phone Restrictions for Young Drivers Review of the Evidence SO TRANSPORTATION RESEARCH RECORD LA English DT Article ID UNITED-STATES; CRASHES; RISK; INTERVENTIONS; BEHAVIOR; IMPACT; LAWS AB This research summarized the effect of cell phone restrictions on the prevalence of cell phone use and motor vehicle crashes involving young drivers. Multiple databases were searched with the use of terms related to cell phone restrictions, the prevalence of cell phone use, crashes, and young drivers. Fifty-three abstracts were reviewed. Eleven studies met the inclusion criteria. Six studies examined changes in the prevalence of cell phone use before and after a restriction was imposed; five studies used changes in crash rates as the outcome. The majority of prevalence studies found no change in young drivers' cell phone use following the introduction of a restriction. Crash studies using multistate samples reported significant reductions in fatal crashes; single-state studies reported no change or small increases in crashes. Restrictions appeared to have no long-term effect on the prevalence of cell phone use among novice drivers. Conflicting findings from crash studies reflected differences in analytical approaches, limitations of existing data, and the challenges of quantifying the effect of young-driver restrictions in the presence of all-driver restrictions. Overall, evidence of the effectiveness of young drivers' cell phone restrictions is inconclusive. There are relatively few studies, and the methodological limitations of the existing studies revealed no clear pattern of effects. Additional studies are needed to distinguish novice drivers (16- to 17-year olds) from experienced young drivers and to use distraction-related crashes as an outcome. C1 [Ehsani, Johnathon P.; Gee, Benjamin T.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, 6100 Execut Blvd,Room 7B13, Bethesda, MD 20892 USA. [Ehsani, Johnathon P.] Johns Hopkins Univ, Bloomberg Sch Publ Hlth, Dept Hlth Policy & Management, 624 North Broadway,Room 557, Baltimore, MD 21205 USA. [Ionides, Edward] Univ Michigan, Coll Literature Sci & Arts, Dept Stat, 453 West Hall,1035 South Univ, Ann Arbor, MI 48109 USA. [Klauer, Sheila G.] Virginia Polytech Inst & State Univ, Virginia Tech Transportat Inst, 3500 Transportat Res Dr, Blacksburg, VA 24061 USA. [Perlus, Jessamyn G.] Univ Illinois, Coll Educ, 210 Educ Bldg,1310 South 6th St, Champaign, IL 61820 USA. RP Ehsani, JP (reprint author), Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, 6100 Execut Blvd,Room 7B13, Bethesda, MD 20892 USA.; Ehsani, JP (reprint author), Johns Hopkins Univ, Bloomberg Sch Publ Hlth, Dept Hlth Policy & Management, 624 North Broadway,Room 557, Baltimore, MD 21205 USA. EM johnathon.ehsani@jhu.edu NR 35 TC 0 Z9 0 U1 1 U2 1 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0361-1981 EI 2169-4052 J9 TRANSPORT RES REC JI Transp. Res. Record PY 2016 IS 2602 BP 35 EP 42 DI 10.3141/2602-05 PG 8 WC Engineering, Civil; Transportation; Transportation Science & Technology SC Engineering; Transportation GA EI8WD UT WOS:000392788000006 ER PT J AU Havas, AP Rodrigues, KB Bhakta, A Demirjian, JA Hahn, S Tran, J Scavello, M Tula-Sanchez, AA Zeng, Y Schmelz, M Smith, CL AF Havas, Aaron P. Rodrigues, Kameron B. Bhakta, Anvi Demirjian, Joseph A. Hahn, Seongmin Tran, Jack Scavello, Margarethakay Tula-Sanchez, Ana A. Zeng, Yi Schmelz, Monika Smith, Catharine L. TI Belinostat and vincristine demonstrate mutually synergistic cytotoxicity associated with mitotic arrest and inhibition of polyploidy in a preclinical model of aggressive diffuse large B cell lymphoma SO CANCER BIOLOGY & THERAPY LA English DT Article DE Cell cycle; drug resistance; histone deacetylase inhibitor; lymphoma; mitosis; microtubule; polyploidy ID HISTONE DEACETYLASE INHIBITORS; SPINDLE ASSEMBLY CHECKPOINT; CANCER-CELLS; HDAC INHIBITORS; OVARIAN-CANCER; IN-VITRO; PERICENTROMERIC HETEROCHROMATIN; ANTIMITOTIC DRUGS; GENE-EXPRESSION; LEUKEMIA-CELLS AB Diffuse Large B-cell lymphoma (DLBCL) is an aggressive malignancy that has a 60 percent 5-year survival rate, highlighting a need for new therapeutic approaches. Histone deacetylase inhibitors (HDACi) are novel therapeutics being clinically-evaluated in combination with a variety of other drugs. However, rational selection of companion therapeutics for HDACi is difficult due to their poorly-understood, cell-type specific mechanisms of action. To address this, we developed a pre-clinical model system of sensitivity and resistance to the HDACi belinostat using DLBCL cell lines. In the current study, we demonstrate that cell lines sensitive to the cytotoxic effects of HDACi undergo early mitotic arrest prior to apoptosis. In contrast, HDACi-resistant cell lines complete mitosis after a short delay and arrest in G1. To force mitotic arrest in HDACi-resistant cell lines, we used low dose vincristine or paclitaxel in combination with belinostat and observed synergistic cytotoxicity. Belinostat curtails vincristine-induced mitotic arrest and triggers a strong apoptotic response associated with downregulated MCL-1 expression and upregulated BIM expression. Resistance to microtubule targeting agents (MTAs) has been associated with their propensity to induce polyploidy and thereby increase the probability of genomic instability that enables cancer progression. Co-treatment with belinostat effectively eliminated a vincristine-induced, actively cycling polyploid cell population. Our study demonstrates that vincristine sensitizes DLBCL cells to the cytotoxic effects of belinostat and that belinostat prevents polyploidy that could cause vincristine resistance. Our findings provide a rationale for using low dose MTAs in conjunction with HDACi as a potential therapeutic strategy for treatment of aggressive DLBCL. C1 [Havas, Aaron P.; Rodrigues, Kameron B.; Bhakta, Anvi; Demirjian, Joseph A.; Scavello, Margarethakay; Tula-Sanchez, Ana A.; Smith, Catharine L.] Univ Arizona, Coll Pharm, Dept Pharmacol & Toxicol, 1703 E Mabel St, Tucson, AZ 85721 USA. [Havas, Aaron P.; Smith, Catharine L.] Univ Arizona, Canc Biol Program, Tucson, AZ USA. [Hahn, Seongmin; Zeng, Yi] Univ Arizona, Coll Med, Dept Pediat, Steele Childrens Res Ctr, Tucson, AZ USA. [Tran, Jack] Univ Arizona, Coll Med, Dept Pathol, Tucson, AZ 85721 USA. [Schmelz, Monika; Smith, Catharine L.] Univ Arizona, Coll Med, Biol Chem Program, Tucson, AZ USA. [Rodrigues, Kameron B.] NIDDK, Immune Tolerance Sect, Diabet Endocrinol & Obes Branch, NIH, Bethesda, MD 20892 USA. RP Smith, CL (reprint author), Univ Arizona, Coll Pharm, Dept Pharmacol & Toxicol, 1703 E Mabel St, Tucson, AZ 85721 USA. EM csmith@pharmacy.arizona.edu FU Arizona Biomedical Research Commission; career development award; developmental project award; cancer biology training grant [T32CA009213]; Cancer Center Support Grant [P30CA023074]; Undergraduate Research Biology Program at the University of Arizona; Hyundai Hope on Wheels Young Investigator Award; SWOG Development Award from the Hope Foundation; [1 P50 CA-130805-05] FX The authors would like to acknowledge the staff of the Flow Cytometry Shared Resource at the Arizona Cancer Center for services rendered. We are grateful to members of the Lymphoma Research Group at the UA for helpful suggestions and critique during the progress of the study. This work was initiated by an award from the Arizona Biomedical Research Commission to C.L.S., and supported through a career development award and developmental project award to C.L.S. [Lymphoma SPORE (1 P50 CA-130805-05, PtdIns - R.I. Fisher)]. A.P.H. received salary support from a cancer biology training grant (T32CA009213) and the Cancer Center Support Grant (P30CA023074). K.B.R. received support from the Undergraduate Research Biology Program at the University of Arizona. Y.Z. received support from a Hyundai Hope on Wheels Young Investigator Award. Salary support for J.T. and M.S. was provided by a SWOG Development Award from the Hope Foundation to M.S. In addition, Spectrum Pharmaceuticals donated belinostat for the study and provided funding to C.L.S. NR 73 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 1538-4047 EI 1555-8576 J9 CANCER BIOL THER JI Cancer Biol. Ther. PY 2016 VL 17 IS 12 BP 1240 EP 1252 DI 10.1080/15384047.2016.1250046 PG 13 WC Oncology SC Oncology GA EI9KR UT WOS:000392827300003 PM 27791595 ER PT J AU Bohannon, JK Honko, AN Reeder, RJ Cooper, K Byrum, R Bollinger, L Kuhn, JH Wada, J Qin, J Jahrling, PB Lackemeyer, MG AF Bohannon, J. Kyle Honko, Anna N. Reeder, Rebecca J. Cooper, Kurt Byrum, Russ Bollinger, Laura Kuhn, Jens H. Wada, Jiro Qin, Jing Jahrling, Peter B. Lackemeyer, Matthew G. TI Comparison of respiratory inductive plethysmography versus head-out plethysmography for anesthetized nonhuman primates in an animal biosafety level 4 facility SO INHALATION TOXICOLOGY LA English DT Article DE ABSL-4; BSL-4; aerobiology; aerosol; plethysmography; respiratory inductive plethysmography ID AEROSOL INHALATION; CALIBRATION; POSITION AB For inhalational studies and aerosol exposures to viruses, head-out plethysmography acquisition has been traditionally used for the determination of estimated inhaled dose in anesthetized nonhuman primates prior to or during an aerosol exposure. A pressure drop across a pneumotachograph is measured within a sealed chamber during inspiration/exhalation of the nonhuman primate, generating respiratory values and breathing frequencies. Due to the fluctuation of depth of anesthesia, pre-exposure respiratory values can be variable, leading to less precise and accurate dosing calculations downstream. Although an anesthesia infusion pump may help stabilize the depth of sedation, pumps are difficult to use within a sealed head-out plethysmography chamber. Real-time, head-out plethysmography acquisition could increase precision and accuracy of the measurements, but the bulky equipment needed for head-out plethysmography precludes real-time use inside a Class III biological safety cabinet, where most aerosol exposures occur. However, the respiratory inductive plethysmography (RIP) acquisition method measures the same respiratory parameters by detecting movement of the chest and abdomen during breathing using two elastic bands within the Class III biological safety cabinet. As respiratory values are relayed to a computer for software integration and analysis real-time, adjustment of aerosol exposure duration is based on the depth of sedation of the animal. The objective of this study was to compare values obtained using two methodologies (pre-exposure head-out plethysmography and real-time RIP). Transitioning to RIP technology with real-time acquisition provides more consistent, precise, and accurate aerosol dosing by reducing reported errors in respiratory values from anesthesia variability when using pre-exposure head-out plethysmography acquisition. C1 [Bohannon, J. Kyle; Honko, Anna N.; Reeder, Rebecca J.; Cooper, Kurt; Byrum, Russ; Bollinger, Laura; Kuhn, Jens H.; Wada, Jiro; Jahrling, Peter B.; Lackemeyer, Matthew G.] NIAID, Integrated Res Facil Ft Detrick, NIH, Frederick, MD USA. [Qin, Jing] NIAID, Biostat Res Branch, NIH, Rockville, MD USA. RP Lackemeyer, MG (reprint author), NIAID, Integrated Res Facil Ft Detrick IRF Frederick, NIH, B-8200 Res Plaza, Ft Detrick, MD 21702 USA. EM matthew.lackemeyer@nih.gov OI Honko, Anna/0000-0001-9165-148X FU Battelle Memorial Institute; US National Institute of Allergy and Infectious Diseases (NIAID) [HHSN272200700016I] FX This work was funded in part through Battelle Memorial Institute's prime contract with the US National Institute of Allergy and Infectious Diseases (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.; M. G. L., an employee of Lovelace Biomedical and Environmental Research Institute; and R. J. R., K. C., and R. B. employees of Charles River Laboratories. NR 25 TC 0 Z9 0 U1 0 U2 0 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. PY 2016 VL 28 IS 14 BP 670 EP 676 DI 10.1080/08958378.2016.1247199 PG 7 WC Toxicology SC Toxicology GA EJ1KC UT WOS:000392968000003 PM 27919178 ER PT J AU Nozadi, SS Troller-Renfree, S White, LK Frenkel, T Degnan, KA Bar-Haim, Y Pine, D Fox, NA AF Nozadi, Sara S. Troller-Renfree, Sonya White, Lauren K. Frenkel, Tahl Degnan, Kathryn A. Bar-Haim, Yair Pine, Daniel Fox, Nathan A. TI The Moderating Role of Attention Biases in understanding the link between Behavioral Inhibition and Anxiety SO Journal of Experimental Psychopathology LA English DT Article DE Attention Biases; Anxiety; Behavioral Inhibition; Temperament ID SOCIAL ANXIETY; EARLY-CHILDHOOD; DEFICIT/HYPERACTIVITY DISORDER; PSYCHOMETRIC PROPERTIES; COGNITIVE PERFORMANCE; CHILDREN; TEMPERAMENT; PSYCHOPATHOLOGY; ADOLESCENTS; WITHDRAWAL AB The current study aimed to extend the results of White et al. (2015) by examining the moderating role of attention biases at age 5 on the relations between Behavioral Inhibition (BI) during toddlerhood and anxiety symptoms at age 10. Children's BI at 2 and 3 years of age was measured using laboratory assessments, and attention bias towards threat was assessed using a dot-probe task at age 5. Latent Class Analysis (LCA) was used to identify the probability for children's membership in an anxiety class, which reflected primary anxiety at age 10 that was not comorbid with symptoms of inattention. Maternal and self-report measures of children's mental health, collected via questionnaires and semi-structured diagnostic interviews, were used as indicators for the LCA. The results revealed that threat-related attention biases moderated the relation between BI and anxiety, such that BI positively predicted the probability of being in the anxiety class only when children had an attention bias towards threat. BI was unrelated to anxiety when children had no attention bias or an attention bias away from threat. These results indicated that attention biases during preschool may differentiate between inhibited children who are at heightened risk for anxiety later in childhood from those who are not. The results are discussed in a framework detailing the role of attention biases in increasing the sensitivity for anxiety-related problems in children who display high levels of BI during early childhood. (C) Copyright 2016 Textrum Ltd. All rights reserved. C1 [Nozadi, Sara S.] Univ New Mexico, Dept Individual Family & Community Educ, Simpson Hall,MSC05 3040, Albuquerque, NM 87131 USA. [Troller-Renfree, Sonya; Fox, Nathan A.] Univ Maryland, Dept Human Dev & Quantitat Methodol, College Pk, MD 20742 USA. [White, Lauren K.; Pine, Daniel] NIMH, Emot & Dev Branch, Bethesda, MD 20892 USA. [Frenkel, Tahl] Ziama Arkin Infancy Inst, Interdisciplinary Ctr, Herzliyya, Israel. [Degnan, Kathryn A.] Catholica Univ, Dept Psychol, Washington, DC USA. [Bar-Haim, Yair] Tel Aviv Univ, Sch Psychol Sci, IL-69978 Tel Aviv, Israel. RP Nozadi, SS (reprint author), Univ New Mexico, Dept Individual Family & Community Educ, Simpson Hall,MSC05 3040, Albuquerque, NM 87131 USA. EM snozadi@unm.edu NR 71 TC 0 Z9 0 U1 2 U2 2 PU TEXTRUM PI LONDON PA 145-157 ST JOHN ST, STE 13719, 2 FL, LONDON, EC1V 4PY, ENGLAND SN 2043-8087 J9 J EXP PSYCHOPATHOL JI J. Exp. Psychopathol. PY 2016 VL 7 IS 3 SI SI BP 451 EP 465 DI 10.5127/jep.052515 PG 15 WC Psychology, Clinical; Psychiatry SC Psychology; Psychiatry GA EI9KQ UT WOS:000392827200011 ER PT J AU Pergamin-Hight, L Bitton, S Pine, DS Fox, NA Bar-Haim, Y AF Pergamin-Hight, Lee Bitton, Shani Pine, Daniel S. Fox, Nathan A. Bar-Haim, Yair TI Attention and Interpretation Biases and Attention Control in Youth with Social Anxiety Disorder SO Journal of Experimental Psychopathology LA English DT Article DE social anxiety; attention bias; interpretation bias; attention control; pediatric anxiety ID DIFFICULTY DISENGAGING ATTENTION; INFORMATION-PROCESSING BIASES; RANDOMIZED CONTROLLED-TRIAL; THREAT-RELEVANT STIMULI; EFFORTFUL CONTROL; ANGRY FACES; PSYCHOPATHOLOGICAL SYMPTOMS; COGNITIVE PERFORMANCE; NONCLINICAL CHILDREN; SELECTIVE ATTENTION AB Social anxiety disorder (SAD) is associated with threat-related attention and interpretation biases. Recent research suggests that attention control abilities moderate these associations. The current study examines threat-related attentional engagement and disengagement biases, negative interpretation bias, and attention control among youth with SAD (n=71) and non-anxious youth (n=42). We further explore interactions between cognitive biases, and between these biases and attention control, in predicting SAD. Relative to non-anxious youth, youth with SAD had poorer attention control, p=.001, greater difficulty disengaging from angry faces, p=.05, and a negative biased interpretation of ambiguous social scenarios, p=.01. However, no interactions were found among these factors in relation to SAD diagnosis or symptoms. The present results add to research on cognitive biases in anxious children, emphasizing a distinct contribution of each of these cognitive mechanisms, rather than their interactional influences. Findings are discussed in relation to cognitive developmental models of anxiety. (C) Copyright 2016 Textrum Ltd. All rights reserved. C1 [Pergamin-Hight, Lee; Bitton, Shani; Bar-Haim, Yair] Tel Aviv Univ, Sch Psychol Sci, IL-69978 Tel Aviv, Israel. [Pine, Daniel S.] NIMH, Intramural Res Program, Emot & Dev Branch, Bethesda, MD 20892 USA. [Fox, Nathan A.] Univ Maryland, Dept Human Dev & Quantitat Methodol, College Pk, MD 20742 USA. [Bar-Haim, Yair] Tel Aviv Univ, Sagol Sch Neurosci, IL-69978 Tel Aviv, Israel. RP Pergamin-Hight, L (reprint author), Tel Aviv Univ, Sch Psychol Sci, IL-69978 Tel Aviv, Israel. EM leepe@post.tau.ac.il FU United States-Israel Binational Science Foundation (BSF) [2009340] FX This work was partially supported by the United States-Israel Binational Science Foundation (BSF, Grant # 2009340). NR 85 TC 0 Z9 0 U1 2 U2 2 PU TEXTRUM PI LONDON PA 145-157 ST JOHN ST, STE 13719, 2 FL, LONDON, EC1V 4PY, ENGLAND SN 2043-8087 J9 J EXP PSYCHOPATHOL JI J. Exp. Psychopathol. PY 2016 VL 7 IS 3 SI SI BP 484 EP 498 DI 10.5127/jep.053115 PG 15 WC Psychology, Clinical; Psychiatry SC Psychology; Psychiatry GA EI9KQ UT WOS:000392827200013 ER PT J AU White, LK Suway, JG Pine, DS Field, AP Lester, KJ Muris, P Bar-Haim, Y Fox, NA AF White, Lauren K. Suway, Jenna G. Pine, Daniel S. Field, Andy P. Lester, Kathryn J. Muris, Peter Bar-Haim, Yair Fox, Nathan A. TI The Cognitive and Emotional Effects of Cognitive Bias Modification in Interpretations in Behaviorally Inhibited Youth SO Journal of Experimental Psychopathology LA English DT Article DE Anxiety; Attention Bias to Threat; Behavioral Inhibition; Cognitive Bias Modification; Negative Interpretative Bias ID GENERALIZED ANXIETY DISORDER; EXPERIMENTAL MANIPULATION; CHILDHOOD ANXIETY; THREAT PERCEPTION; ATTENTIONAL BIAS; ANIMAL FEAR; CHILDREN; VULNERABILITY; INFORMATION; REACTIVITY AB Cognitive bias modification (CBM) procedures follow from the view that interpretive biases play an important role in the development and maintenance of anxiety. As such, understanding the link between interpretive biases and anxiety in youth at risk for anxiety (e.g., behaviorally inhibited children) could elucidate the mechanisms involved in the development of pediatric anxiety. However, to date, the majority of CBM-I work only studies adult populations. The present article presents the results of a CBM study examining effects of positive interpretive bias modification on mood, stress vulnerability, and threat-related attention bias in a group of behaviorally inhibited children (n = 45). Despite successful modification of interpretive bias in the at-risk youth, minimal effects on stress vulnerability or threat-related attention bias were found. The current findings highlight the need for continued research on cognitive biases in anxiety. (C) Copyright 2016 Textrum Ltd. All rights reserved. C1 [White, Lauren K.; Pine, Daniel S.] NIMH, Emot & Dev Branch, Bethesda, MD 20892 USA. [Suway, Jenna G.] San Diego State Univ, SDSU UCSD Joint Doctoral Program Clin Psychol, San Diego, CA 92182 USA. [Field, Andy P.; Lester, Kathryn J.] Univ Sussex, Sch Psychol, Brighton BN1 9RH, E Sussex, England. [Muris, Peter] Univ Rotterdam, Inst Psychol, Rotterdam, Netherlands. [Bar-Haim, Yair] Tel Aviv Univ, Dept Psychol, IL-69978 Tel Aviv, Israel. [Fox, Nathan A.] Univ Maryland, Dept Human Dev & Quantitat Methodol, College Pk, MD 20742 USA. RP White, LK (reprint author), NIMH, Bldg 15K,MSC 2670, Bethesda, MD 20892 USA. EM lauren.white@nih.gov FU National Institute of Mental Health [1F31MH085424] FX This work was supported in part by the National Institute of Mental Health under grant 1F31MH085424 NR 46 TC 0 Z9 0 U1 0 U2 0 PU TEXTRUM PI LONDON PA 145-157 ST JOHN ST, STE 13719, 2 FL, LONDON, EC1V 4PY, ENGLAND SN 2043-8087 J9 J EXP PSYCHOPATHOL JI J. Exp. Psychopathol. PY 2016 VL 7 IS 3 SI SI BP 499 EP 510 DI 10.5127/jep.053615 PG 12 WC Psychology, Clinical; Psychiatry SC Psychology; Psychiatry GA EI9KQ UT WOS:000392827200014 ER PT J AU Waters, AM Zimmer-Gembeck, MJ Craske, MG Pine, DS Bradley, BP Mogg, K AF Waters, Allison M. Zimmer-Gembeck, Melanie J. Craske, Michelle G. Pine, Daniel S. Bradley, Brendan P. Mogg, Karin TI A Preliminary Evaluation of a Home-based, Computer-delivered Attention Training Treatment for Anxious Children Living in Regional Communities SO Journal of Experimental Psychopathology LA English DT Article DE Anxiety; children; attention; modification ID DISORDERS INTERVIEW SCHEDULE; CHILDHOOD ANXIETY DISORDERS; COGNITIVE BIAS MODIFICATION; RANDOMIZED CONTROLLED-TRIAL; MENTAL-HEALTH PROBLEMS; ASSESSMENT SCALE CGAS; GLOBAL ASSESSMENT; POSITIVE STIMULI; PARENT VERSIONS; SOCIAL PHOBIA AB Many children with anxiety disorders live in communities with limited access to treatment. Attention bias modification training, a promising computer-based treatment for anxiety disorders, may provide a readily accessible treatment. Recent evidence suggests that a form of ABMT combining visual-search for positive stimuli with features to enhance learning, memory and treatment engagement reduces anxiety in children. The present study builds upon this research by comparing parent-implemented, visual-search attention training to positive stimuli (ATP) (N = 22) with a waitlist control group (WLC) (N = 19) in children living in regional communities. Diagnostic, parent-and child-reports of anxiety and depressive symptoms and broad internalizing and externalizing behaviour problems were assessed pre-and post-condition. Children in the WLC completed visual-search ATP after the wait period and all participants completed a follow-up assessment six-months after treatment. At post-treatment/ wait period, children in the ATP condition showed greater improvements on clinician-and parent-report measures compared to children in the WLC. Similar post-treatment outcomes as those found for the ATP condition were observed at the six-month follow-up after all children had received ATP. Moreover, children who showed greater verbalization of explicit attention strategies related to positive search (assessed during treatment) achieved greater reductions in anxiety severity at post-treatment and six-month follow-up. Attention training towards positive stimuli using enhanced visual-search procedures appears to be a promising treatment for reaching anxious children living in regional communities. (C) Copyright 2016 Textrum Ltd. All rights reserved. C1 [Waters, Allison M.; Zimmer-Gembeck, Melanie J.] Griffith Univ, Sch Appl Psychol, Nathan, Qld 4111, Australia. [Craske, Michelle G.] Univ Calif Los Angeles, Dept Psychol, Los Angeles, CA USA. [Pine, Daniel S.] NIMH, Bethesda, MD 20892 USA. [Bradley, Brendan P.; Mogg, Karin] Univ Southampton, Psychol, Southampton SO9 5NH, Hants, England. RP Waters, AM (reprint author), Griffith Univ, Sch Appl Psychol, Nathan, Qld 4111, Australia. EM a.waters@griffith.edu.au FU Australian Research Council [DP120101678] FX This research was supported by funding awarded to the authors by the Australian Research Council (DP120101678). Thanks are due to Ms Emily Seager, Ms Emily Allan and Mr Xuesong Le and the team of clinicians who served as independent assessors during this project. NR 49 TC 0 Z9 0 U1 3 U2 3 PU TEXTRUM PI LONDON PA 145-157 ST JOHN ST, STE 13719, 2 FL, LONDON, EC1V 4PY, ENGLAND SN 2043-8087 J9 J EXP PSYCHOPATHOL JI J. Exp. Psychopathol. PY 2016 VL 7 IS 3 SI SI BP 511 EP 527 DI 10.5127/jep.053315 PG 17 WC Psychology, Clinical; Psychiatry SC Psychology; Psychiatry GA EI9KQ UT WOS:000392827200015 ER PT J AU Bachmann, C Kasper, S AF Bachmann, Christoph Kasper, Siegfried TI Phytotherapy and Phytopharmaceuticals: Expert Interview with Prof. Dr. Siegfried Kasper SO Schweizerische Zeitschrift fuer Ganzheitsmedizin LA German DT Editorial Material C1 [Bachmann, Christoph] Hirschmattstr 46, CH-FAX +497 Luzern, Switzerland. [Kasper, Siegfried] Med Univ Wien, Univ Klin Psychiat & Psychotherapie, Vienna, Austria. [Kasper, Siegfried] NIMH, Bethesda, MD 20892 USA. [Kasper, Siegfried] Univ Klin Bonn, Psychiat, Bonn, Germany. [Kasper, Siegfried] Univ Vienna, Psychiat, A-1010 Vienna, Austria. RP Bachmann, C (reprint author), Hirschmattstr 46, CH-FAX +497 Luzern, Switzerland. EM c.a.bachmann@bluewin.ch NR 0 TC 0 Z9 0 U1 0 U2 0 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 1015-0684 EI 1663-7607 J9 SCHWEIZ Z GANZHEITSM JI Schweiz. Z. Ganzheitsmed. PY 2016 VL 28 IS 5 BP 254 EP 257 DI 10.1159/000448678 PG 4 WC Integrative & Complementary Medicine SC Integrative & Complementary Medicine GA EI9EI UT WOS:000392809900002 ER PT J AU Halland, F Morken, NH DeRoo, LA Klungsoyr, K Wilcox, AJ Skjaerven, R AF Halland, Frode Morken, Nils-Halvdan DeRoo, Lisa A. Klungsoyr, Kari Wilcox, Allen J. Skjaerven, Rolv TI Long-term mortality in mothers with perinatal losses and risk modification by surviving children and attained education: a population-based cohort study (vol 6, e012894, 2016) SO BMJ OPEN LA English DT Correction C1 [Halland, Frode; Morken, Nils-Halvdan; DeRoo, Lisa A.; Klungsoyr, Kari; Skjaerven, Rolv] Univ Bergen, Dept Global Publ Hlth & Primary Care, Bergen, Norway. [Halland, Frode; Morken, Nils-Halvdan] Haukeland Hosp, Dept Obstet & Gynecol, Bergen, Norway. [Morken, Nils-Halvdan] Univ Bergen, Dept Clin Sci, Bergen, Norway. [DeRoo, Lisa A.; Wilcox, Allen J.] NIEHS, Epidemiol Branch, NIH, Durham, NC USA. [Klungsoyr, Kari; Skjaerven, Rolv] Norwegian Inst Publ Hlth, Med Birth Registry Norway, Bergen, Norway. RP Halland, F (reprint author), Univ Bergen, Dept Global Publ Hlth & Primary Care, Bergen, Norway.; Halland, F (reprint author), Haukeland Hosp, Dept Obstet & Gynecol, Bergen, Norway. NR 1 TC 0 Z9 0 U1 0 U2 0 PU BMJ PUBLISHING GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 2044-6055 J9 BMJ OPEN JI BMJ Open PY 2016 VL 6 IS 12 AR e012894corr1 DI 10.1136/bmjopen-2016-012894corr1 PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA EG8JS UT WOS:000391303600026 ER PT J AU Asare, P Chowdhury, MA Rajah, T Poler, SM Shah, M Guion, P Martin, J Driscoll, K Wu, QH Mannes, A Nataraj, C AF Asare, Philip Chowdhury, Mahmood Arifin Rajah, Taimoore Poler, S. Mark Shah, Mohammed Guion, Peter Martin, Jeffrey Driscoll, Kevin Wu, Qianhong Mannes, Andrew Nataraj, C. GP IEEE TI A System for Semi-Automated Management of Blood Loss during Surgery: Preliminary Results SO 2016 IEEE HEALTHCARE INNOVATION POINT-OF-CARE TECHNOLOGIES CONFERENCE (HI-POCT) LA English DT Proceedings Paper CT NIH-IEEE Strategic Conference on Healthcare Innovations and Point-of-Care (POC) Technologies CY NOV 09-11, 2016 CL Cancun, MEXICO SP IEEE, NIH ID FLUID RESUSCITATION; COLLOIDS; THERAPY; SHOCK AB This paper presents preliminary results from a pilot study for automated management of blood loss during surgery. The paper describes our approach in developing mathematical models for the cardiovascular system including blood loss and use of colloids for resuscitation. Further, adaptive models are synthesized and used for designing appropriate control algorithms. These algorithms are further integrated into a computerized platform that interfaces with medical devices such as monitors and pumps, which will be tested and validated in animal trials. The eventual development will be minimalist with an open architecture in order to enable easy adoption by others in the community. C1 [Asare, Philip] Bucknell Univ, Elect & Comp Engn, Lewisburg, PA 17837 USA. [Asare, Philip] Bucknell Univ, Sci & Engn, Lewisburg, PA 17837 USA. [Rajah, Taimoore; Driscoll, Kevin; Mannes, Andrew] NIH, Dept Perioperat Med, Bldg 10, Bethesda, MD 20892 USA. [Poler, S. Mark] Geisinger Hlth Syst, Anesthesiol, Danville, PA 17822 USA. [Chowdhury, Mahmood Arifin] Villanova Univ, Villanova, PA 19085 USA. [Wu, Qianhong] Villanova Univ, Mech Engn, Villanova, PA 19085 USA. [Shah, Mohammed; Martin, Jeffrey] NIH, Ctr Clin, Bethesda, MD 20892 USA. [Guion, Peter] Natl Canc Inst, Radiat Oncol, Bethesda, MD USA. [Nataraj, C.] Villanova Univ, Villanova Ctr Analyt Dynam Syst, Villanova, PA 19085 USA. RP Asare, P (reprint author), Bucknell Univ, Elect & Comp Engn, Lewisburg, PA 17837 USA.; Asare, P (reprint author), Bucknell Univ, Sci & Engn, Lewisburg, PA 17837 USA. EM philip.asare@bucknell.edu; mchowdh1@villanova.edu; rajahtm@cc.nih.gov; m.poler@ieee.org; mohammad.shah@nih.gov; peter.guion@nih.gov; jeffrey.martin@nih.gov; kevin.driscoll@nih.gov; qianhong.wu@villanova.edu; amannes@mail.nih.gov; nataraj@villanova.edu FU Bucknell-Geisinger Research Initiative Phase IV [GPE094] FX This research is sponsored in part by Bucknell-Geisinger Research Initiative Phase IV Grant No. GPE094. NR 22 TC 0 Z9 0 U1 0 U2 0 PU IEEE PI NEW YORK PA 345 E 47TH ST, NEW YORK, NY 10017 USA BN 978-1-5090-1166-7 PY 2016 BP 216 EP 219 PG 4 WC Engineering, Biomedical SC Engineering GA BG7XT UT WOS:000391944200051 ER PT J AU Holzinger, E Szymcak, S Malley, J Dasgupta, A Li, Q Bailey-Wilson, JE AF Holzinger, Emily Szymcak, Silke Malley, James Dasgupta, Abhijit Li, Qing Bailey-Wilson, Joan E. TI r2VIM: Variable Selection Method for Identifying Interaction Effects SO HUMAN HEREDITY LA English DT Meeting Abstract CT Symposium of Advances in Genomics, Epidemiology and Statistics (SAGES) CY MAY 29, 2015 CL Philadelphia, PA C1 [Holzinger, Emily; Szymcak, Silke; Malley, James; Dasgupta, Abhijit; Li, Qing; Bailey-Wilson, Joan E.] NHGRI, Computat & Stat Genom Branch, NIH, Baltimore, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 0001-5652 EI 1423-0062 J9 HUM HERED JI Hum. Hered. PY 2016 VL 81 IS 2 MA 11 BP 54 EP 54 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA EI5UF UT WOS:000392559600012 ER PT J AU Hua, X Hyland, PL Huang, J Zhu, B Caporaso, NE Landi, MT Chatterjee, N Shi, JX AF Hua, Xing Hyland, Paula L. Huang, Jing Zhu, Bin Caporaso, Neil E. Landi, Maria Teresa Chatterjee, Nilanjan Shi, Jianxin TI MEGSA: A Powerful and Flexible Framework for Analyzing Mutual Exclusivity of Tumor Mutations SO HUMAN HEREDITY LA English DT Meeting Abstract CT Symposium of Advances in Genomics, Epidemiology and Statistics (SAGES) CY MAY 29, 2015 CL Philadelphia, PA C1 [Hua, Xing; Zhu, Bin; Chatterjee, Nilanjan; Shi, Jianxin] NCI, Biostat Branch, Div Canc Epidemiol & Genet, NIH, Bethesda, MD 20892 USA. [Hyland, Paula L.; Caporaso, Neil E.; Landi, Maria Teresa] NCI, Genet Epidemiol Branch, Div Canc Epidemiol & Genet, NIH, Bethesda, MD 20892 USA. [Huang, Jing] NCI, Lab Canc Biol & Genet, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 0001-5652 EI 1423-0062 J9 HUM HERED JI Hum. Hered. PY 2016 VL 81 IS 2 MA 12 BP 54 EP 54 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA EI5UF UT WOS:000392559600013 ER PT J AU Li, Q Holzinger, E Bailey-Wilson, JE AF Li, Qing Holzinger, Emily Bailey-Wilson, Joan E. TI Modified Random Forest Algorithm to Identify GxG Interaction in Matched Case-Control and Case-Parent Trios Studies SO HUMAN HEREDITY LA English DT Meeting Abstract CT Symposium of Advances in Genomics, Epidemiology and Statistics (SAGES) CY MAY 29, 2015 CL Philadelphia, PA C1 [Li, Qing; Holzinger, Emily; Bailey-Wilson, Joan E.] NHGRI, Stat Genet Sect, Computat & Stat Genom Branch, NIH, Baltimore, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 0001-5652 EI 1423-0062 J9 HUM HERED JI Hum. Hered. PY 2016 VL 81 IS 2 MA 17 BP 56 EP 56 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA EI5UF UT WOS:000392559600018 ER PT J AU Mullooly, M Pfeiffer, RM Nyante, SJ Brinton, L Hoover, RN Glass, A de Gonzalez, AB Sherman, ME Gierach, GL AF Mullooly, Maeve Pfeiffer, Ruth M. Nyante, Sarah J. Brinton, Louise Hoover, Robert N. Glass, Andrew de Gonzalez, Amy Berrington Sherman, Mark E. Gierach, Gretchen L. TI Conservation of Genomic Characteristics in Primary and Contralateral Breast Tumors SO HUMAN HEREDITY LA English DT Meeting Abstract CT Symposium of Advances in Genomics, Epidemiology and Statistics (SAGES) CY MAY 29, 2015 CL Philadelphia, PA C1 [Mullooly, Maeve; Pfeiffer, Ruth M.; Brinton, Louise; Hoover, Robert N.; Gierach, Gretchen L.] NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. [Mullooly, Maeve] NCI, Canc Prevent Fellowship Program, Canc Prevent Div, Bethesda, MD 20892 USA. [Nyante, Sarah J.] Univ N Carolina, Sch Med, Dept Radiol, Chapel Hill, NC 27514 USA. [Glass, Andrew] Grp Hlth Res Inst, Seattle, WA USA. [de Gonzalez, Amy Berrington] Kaiser Permanente Northwest Ctr Hlth Res, Portland, OR USA. [Sherman, Mark E.] NCI, Breast & Gynecol Canc Res Grp, Canc Prevent Div, Bethesda, MD 20892 USA. RI Gierach, Gretchen/E-1817-2016 OI Gierach, Gretchen/0000-0002-0165-5522 NR 0 TC 0 Z9 0 U1 0 U2 0 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 0001-5652 EI 1423-0062 J9 HUM HERED JI Hum. Hered. PY 2016 VL 81 IS 2 MA 18 BP 57 EP 57 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA EI5UF UT WOS:000392559600019 ER PT J AU Simpson, CL AF Simpson, Claire L. TI Linkage Analysis of Whole Exome Sequence Data in Multiplex Autism Families Including Cholesterol Covariates SO HUMAN HEREDITY LA English DT Meeting Abstract CT Symposium of Advances in Genomics, Epidemiology and Statistics (SAGES) CY MAY 29, 2015 CL Philadelphia, PA C1 [Simpson, Claire L.] Natl Human Genome Res Inst, Stat Genet Sect, Computat & Stat Genom Branch, NIH, Baltimore, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 0001-5652 EI 1423-0062 J9 HUM HERED JI Hum. Hered. PY 2016 VL 81 IS 2 MA 22 BP 58 EP 58 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA EI5UF UT WOS:000392559600023 ER PT J AU Hua, X Goedert, JJ Landi, MT Shi, JX AF Hua, Xing Goedert, James J. Landi, Maria Teresa Shi, Jianxin TI Identifying Host Genetic Variants Associated with Microbiorne Composition by Testing Multiple Beta Diversity Matrices SO HUMAN HEREDITY LA English DT Article; Proceedings Paper CT Symposium of Advances in Genomics, Epidemiology and Statistics (SAGES) CY MAY 29, 2015 CL Philadelphia, PA DE Microbiome; Genome-wide association study; Host genetics; Tail probabilities; Skewness; Kurtosis ID GUT MICROBIOME; UNIFRAC; CANCER; COMMUNITIES AB Objectives: Host genetics have been recently reported to affect human microbiome composition. We previously developed a statistical framework, microbiomeGWAS, to identify host genetic variants associated with microbiome composition by testing a distance matrix. However, statistical power depends on the choice of a microbiome distance matrix. To achieve more robust statistical power, we aim to extend microbiomeGWAS to test the association with many distance matrices, which are defined based on multilevel taxa abundances and phylogenetic information. Methods: The main challenge is to accurately and rapidly evaluate the significance for millions of SNPs. We propose methods for approximating p values by correcting for the multiple testing introduced by testing many distance matrices and by correcting for the skewness and kurtosis of score statistics. Results: The accuracy of p value approximation was verified by simulations. We applied our method to a set of 147 lung cancer patients with 16S rRNA microbiome profiles from nonmalignant lung tissues. We show that correcting for skewness and kurtosis eliminated dramatic deviations in the quantile-quantile plot. Conclusion: We developed computationally efficient methods for identifying host genetic variants associated with microbiome composition by testing many distance matrices. The algorithms are implemented in the package microbiomeGWAS (https://github.com/IsncibbinnicrobionneGWAS). (C) 2017 S. Karger AG, Basel C1 [Hua, Xing; Goedert, James J.; Landi, Maria Teresa; Shi, Jianxin] NCI, Div Canc Epidemiol & Genet, NIH, Bethesda, MD USA. EM Jiandn.Shi@nih.gov FU NIH Intramural Research program FX This study utilized the high-performance computational capabilities of the Biowulf Linux cluster at the National Institutes of Health, Bethesda, MD (http://biowulf.nih.gov). The project was supported by the NIH Intramural Research program. The authors thank Dr. Mitchell H. Gail from the National Cancer Institute for valuable suggestions to the project. NR 34 TC 0 Z9 0 U1 0 U2 0 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 0001-5652 EI 1423-0062 J9 HUM HERED JI Hum. Hered. PY 2016 VL 81 IS 2 BP 117 EP 126 DI 10.1159/000448733 PG 10 WC Genetics & Heredity SC Genetics & Heredity GA EI5UF UT WOS:000392559600032 PM 28076867 ER PT J AU Salerno, EP Bedognetti, D Mauldin, IS Deacon, DH Shea, SM Pinczewski, J Obeid, JM Coukos, G Wang, E Gajewski, TF Marincola, FM Slingluff, CL AF Salerno, Elise P. Bedognetti, Davide Mauldin, Ileana S. Deacon, Donna H. Shea, Sofia M. Pinczewski, Joel Obeid, Joseph M. Coukos, George Wang, Ena Gajewski, Thomas F. Marincola, Francesco M. Slingluff, Craig L., Jr. TI Human melanomas and ovarian cancers overexpressing mechanical barrier molecule genes lack immune signatures and have increased patient mortality risk SO ONCOIMMUNOLOGY LA English DT Article DE Adherens junction; cancer immunology; desmosome; filaggrin; immune privilege; immunosuppression; melanoma; ovarian cancer; TIL; tumor microenvironment ID ENDOTHELIN-B RECEPTOR; METASTATIC MELANOMA; LUNG-CANCER; T-CELLS; INDUCED IMMUNOSUPPRESSION; PROGNOSTIC MARKER; EXPRESSION; MIGRATION; SURVIVAL; THERAPY AB We have identified eight genes whose expression in human melanoma metastases and ovarian cancers is associated with a lack of Th1 immune signatures. They encode molecules with mechanical barrier function in the skin and other normal tissues and include filaggrin (FLG), tumor-associated calcium signal transducer 2 (TACSTD2), and six desmosomal proteins (DST, DSC3, DSP, PPL, PKP3, and JUP). This association has been validated in an independent series of 114 melanoma metastases. In these, DST expression alone is sufficient to identify melanomas without immune signatures, while FLG and the other six putative barrier molecules are overexpressed in a different subset of melanomas lacking immune signatures. Similar associations have been identified in a set of 186 ovarian cancers. RNA-seq data from 471 melanomas and 307 ovarian cancers in the TCGA database further support these findings and also reveal that overexpression of barrier molecules is strongly associated with early patient mortality for melanoma (p = 0.0002) and for ovarian cancer (p < 0.01). Interestingly, this association persists for FLG for melanoma (p = 0.012) and ovarian cancer (p = 0.006), whereas DST overexpression is negatively associated with CD8(+) gene expression, but not with patient survival. Thus, overexpression of FLG or DST identifies two distinct patient populations with low immune cell infiltration in these cancers, but with different prognostic implications for each. These data raise the possibility that molecules with mechanical barrier function in skin and other tissues may be used by cancer cells to protect them from immune cell infiltration and immune-mediated destruction. C1 [Salerno, Elise P.; Mauldin, Ileana S.; Deacon, Donna H.; Shea, Sofia M.; Pinczewski, Joel; Obeid, Joseph M.; Slingluff, Craig L., Jr.] Univ Virginia, Dept Surg, Div Surg Oncol, POB 800709, Charlottesville, VA 22908 USA. [Bedognetti, Davide] NIH, IDIS, Dept Transfus Med, Ctr Clin, Bldg 10, Bethesda, MD 20892 USA. [Bedognetti, Davide] NIH, Trans NIH Ctr Human Immunol CHI, Bldg 10, Bethesda, MD 20892 USA. [Bedognetti, Davide; Wang, Ena; Marincola, Francesco M.] Sidra Med & Res Ctr, Doha, Qatar. [Shea, Sofia M.] Univ Virginia Hlth Syst, Dept Pathol, Charlottesville, VA USA. [Coukos, George] Univ Lausanne, Ludwig Inst Canc Res, Lausanne, Switzerland. [Gajewski, Thomas F.] Univ Chicago, Dept Med, Chicago, IL 60637 USA. [Salerno, Elise P.] Univ Alabama Birmingham, Surg, Birmingham, AL USA. [Shea, Sofia M.] Hunter Holmes McGuire Vet Adm Hosp, Dermatopathol, Richmond, VA USA. [Shea, Sofia M.] Hunter Holmes McGuire Vet Adm Hosp, Richmond, VA USA. RP Slingluff, CL (reprint author), Univ Virginia, Dept Surg, Div Surg Oncol, POB 800709, Charlottesville, VA 22908 USA. EM cls8h@virginia.edu FU National Institutes of Health Research Training Grant [T32CA163177-01]; Intramural Research Program of the National Institutes of Health; Conquer Cancer Foundation of the American Society of Clinical Oncology; University of Virginia Rebecca Clay Harris Memorial Fellowship; University of Virginia Beirne Carter Center for Immunology Research Fellowship Training Grant [T32 AI007496]; University of Virginia Cancer Center Support [NIH/NCI P30 CA44579] FX Funding support was provided by the National Institutes of Health Research Training Grant T32CA163177-01 (PI, Slingluff, Jones; ES), the Intramural Research Program of the National Institutes of Health (DB, FM), the Conquer Cancer Foundation of the American Society of Clinical Oncology (2011 Young Investigator Award to DB), the University of Virginia Rebecca Clay Harris Memorial Fellowship (SS) and the University of Virginia Beirne Carter Center for Immunology Research Fellowship Training Grant T32 AI007496 (JP). This work was also funded in part by the University of Virginia Cancer Center Support Grant NIH/NCI P30 CA44579 (Biorepository and Tissue Procurement Facility). NR 54 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 2162-402X J9 ONCOIMMUNOLOGY JI OncoImmunology PY 2016 VL 5 IS 12 AR e1240857 DI 10.1080/2162402X.2016.1240857 PG 14 WC Oncology; Immunology SC Oncology; Immunology GA EI9RI UT WOS:000392846200012 PM 28123876 ER PT S AU Anderson, A Smith, E Gandjbakhche, A AF Anderson, Afrouz Smith, Elizabeth Gandjbakhche, Amir GP IEEE TI Prefrontal cortex hemodynamics and age in children: a pilot study using functional near infrared spectroscopy SO 2016 CONFERENCE ON LASERS AND ELECTRO-OPTICS (CLEO) SE Conference on Lasers and Electro-Optics LA English DT Proceedings Paper CT Conference on Lasers and Electro-Optics (CLEO) CY JUN 05-10, 2016 CL San Jose, CA ID CEREBRAL HEMODYNAMICS; FREQUENCY; OSCILLATIONS; SIGNAL AB We introduce a novel parameter, Oxygenation Variability Index, obtained from functional near infrared spectroscopy data. The pilot study in children reveal a dynamic relationship between age and OV index in frequencies associated with cerebral autoregulation. C1 [Anderson, Afrouz; Smith, Elizabeth; Gandjbakhche, Amir] NICHHD, NIH, 9000 Rockville Pike, Bethesda, MD 20890 USA. RP Gandjbakhche, A (reprint author), NICHHD, NIH, 9000 Rockville Pike, Bethesda, MD 20890 USA. EM gandjbaa@mail.nih.gov NR 11 TC 0 Z9 0 U1 0 U2 0 PU IEEE PI NEW YORK PA 345 E 47TH ST, NEW YORK, NY 10017 USA SN 2160-9020 BN 978-1-9435-8011-8 J9 CONF LASER ELECTR PY 2016 PG 2 WC Engineering, Electrical & Electronic; Optics; Physics, Applied SC Engineering; Optics; Physics GA BG7HE UT WOS:000391286400126 ER PT S AU Borovikov, E Yershov, S AF Borovikov, Eugene Yershov, Sergey BE Samsonovich, AV Klimov, VV TI On Virtual Characters that Can See SO 7TH ANNUAL INTERNATIONAL CONFERENCE ON BIOLOGICALLY INSPIRED COGNITIVE ARCHITECTURES, (BICA 2016) SE Procedia Computer Science LA English DT Proceedings Paper CT 7th Annual International Conference on Biologically Inspired Cognitive Architectures (BICA) CY JUL 16-19, 2016 CL New York City, NY DE cognitive architecture; virtual character; computer vision ID NETWORK; ARCHITECTURE; RECOGNITION AB A virtual character (VC) acts within its virtual world boundaries, but with vision sensory capabilities, it may be expected to explore the real world and interact with the intelligent beings there. Such a VC can be equipped with algorithms to localize humans, recognize and communicate with them. These perceptual capabilities prompt a sophisticated cognitive architecture (CA), enabling our VC to learn from intelligent beings and perhaps reason like one. This CA needs to be fairly seamless, reliable and adaptive. Here we explore a vision-based human-centric approach to the VC design. C1 [Borovikov, Eugene; Yershov, Sergey] PercepReal, Ellicott City, MD 21043 USA. [Borovikov, Eugene] NIH, Bldg 10, Bethesda, MD 20892 USA. RP Borovikov, E (reprint author), PercepReal, Ellicott City, MD 21043 USA.; Borovikov, E (reprint author), NIH, Bldg 10, Bethesda, MD 20892 USA. EM Borovikov@PercepReal.com; Yershov@PercepReal.com NR 20 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA SARA BURGERHARTSTRAAT 25, PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 1877-0509 J9 PROCEDIA COMPUT SCI PY 2016 VL 88 BP 528 EP 533 DI 10.1016/j.procs.2016.07.475 PG 6 WC Computer Science, Hardware & Architecture; Computer Science, Interdisciplinary Applications; Computer Science, Software Engineering SC Computer Science GA BG7TD UT WOS:000391723200078 ER PT J AU Wankhade, UD Shen, M Yadav, H Thakali, KM AF Wankhade, Umesh D. Shen, Michael Yadav, Hariom Thakali, Keshari M. TI Novel Browning Agents, Mechanisms, and Therapeutic Potentials of Brown Adipose Tissue SO BIOMED RESEARCH INTERNATIONAL LA English DT Review ID DIET-INDUCED OBESITY; IMPROVES INSULIN SENSITIVITY; ENERGY HOMEOSTASIS; WHITE FAT; GLUCOSE-HOMEOSTASIS; GUT MICROBIOTA; ADULT HUMANS; BEIGE FAT; METABOLIC SYNDROME; COLD-EXPOSURE AB Nonshivering thermogenesis is the process of biological heat production in mammals and is primarily mediated by brown adipose tissue (BAT). Through ubiquitous expression of uncoupling protein 1 (Ucp1) on the mitochondrial inner membrane, BAT displays uncoupling of fuel combustion and ATP production in order to dissipate energy as heat. Because of its crucial role in regulating energy homeostasis, ongoing exploration of BAT has emphasized its therapeutic potential in addressing the global epidemics of obesity and diabetes. The recent appreciation that adult humans possess functional BAT strengthens this prospect. Furthermore, it has been identified that there are both classical brown adipocytes residing in dedicated BAT depots and "beige" adipocytes residing in white adipose tissue depots that can acquire BAT-like characteristics in response to environmental cues. This review aims to provide a brief overview of BAT research and summarize recent findings concerning the physiological, cellular, and developmental characteristics of brown adipocytes. In addition, some key genetic, molecular, and pharmacologic targets of BAT/Beige cells that have been reported to have therapeutic potential to combat obesity will be discussed. C1 [Wankhade, Umesh D.; Thakali, Keshari M.] Arkansas Childrens Nutr Ctr, Little Rock, AR USA. [Wankhade, Umesh D.; Thakali, Keshari M.] Univ Arkansas Med Sci, Dept Pediat, Little Rock, AR 72205 USA. [Shen, Michael] Duke Univ, Durham, NC USA. [Yadav, Hariom] NIH, Diabet Endocrinol & Obes Branch, Bldg 10, Bethesda, MD 20892 USA. RP Wankhade, UD (reprint author), Arkansas Childrens Nutr Ctr, Little Rock, AR USA.; Wankhade, UD (reprint author), Univ Arkansas Med Sci, Dept Pediat, Little Rock, AR 72205 USA. EM udvets@gmail.com OI Wankhade, Umesh/0000-0003-4810-221X; Yadav, Hariom/0000-0003-4504-1597 FU USDA-ARS Project [6026-51000-010-05S] FX The authors thank Dr. Sean Adams for helpful comments and suggestions while drafting the manuscript. Umesh D. Wankhade and Keshari M. Thakali are supported by USDA-ARS Project 6026-51000-010-05S. NR 109 TC 0 Z9 0 U1 3 U2 3 PU HINDAWI PUBLISHING CORP PI NEW YORK PA 315 MADISON AVE 3RD FLR, STE 3070, NEW YORK, NY 10017 USA SN 2314-6133 EI 2314-6141 J9 BIOMED RES INT JI Biomed Res. Int. PY 2016 AR 2365609 DI 10.1155/2016/2365609 PG 15 WC Biotechnology & Applied Microbiology; Medicine, Research & Experimental SC Biotechnology & Applied Microbiology; Research & Experimental Medicine GA EH7YV UT WOS:000391989500001 ER PT J AU Halland, F Morken, NH Deroo, LA Klungsoyr, K Wilcox, AJ Skjaerven, R AF Halland, Frode Morken, Nils-Halvdan Deroo, Lisa A. Klungsoyr, Kari Wilcox, Allen J. Skjaerven, Rolv TI Long-term mortality in mothers with perinatal losses and risk modification by surviving children and attained education: a population-based cohort study SO BMJ OPEN LA English DT Article ID ANTEPARTUM FETAL-DEATH; FOLLOW-UP; CARDIOVASCULAR MORTALITY; STILLBIRTH; PARENTS; BEREAVEMENT; COUNTRIES; ANXIETY; DISEASE; INFANT AB Objective: To assess the association between perinatal losses and mother's long-term mortality and modification by surviving children and attained education. Design: A population-based cohort study. Setting: Norwegian national registries. Participants: We followed 652 320 mothers with a first delivery from 1967 and completed reproduction before 2003, until 2010 or death. We excluded mothers with plural pregnancies, without information on education (0.3%) and women born outside Norway. Main outcome measures: Main outcome measures were age-specific (40-69 years) cardiovascular and non-cardiovascular mortality. We calculated mortality in mothers with perinatal losses, compared with mothers without, and in mothers with one loss by number of surviving children in strata of mothers' attained education (<11 years (low), >= 11 years (high)). Results: Mothers with perinatal losses had increased crude mortality compared with mothers without; total: HR 1.3 (95% CI 1.3 to 1.4), cardiovascular: HR 1.8 (1.5 to 2.1), non-cardiovascular: HR 1.3 (1.2 to 1.4). Childless mothers with one perinatal loss had increased mortality compared with mothers with one child and no loss; cardiovascular: low education HR 2.7 (1.7 to 4.3), high education HR 0.91 (0.13 to 6.5); non-cardiovascular: low education HR 1.6 (1.3 to 2.2), high education HR 1.8 (1.1 to 2.9). Mothers with one perinatal loss, surviving children and high education had no increased mortality, whereas corresponding mothers with low education had increased mortality; cardiovascular: two surviving children HR 1.7 (1.2 to 2.4), three or more surviving children HR 1.6 (1.1 to 2.4); non-cardiovascular: one surviving child HR 1.2 (1.0 to 1.5), two surviving children HR 1.2 (1.1 to 1.4). Conclusions: Irrespective of education, we find excess mortality in childless mothers with a perinatal loss. Increased mortality in mothers with one perinatal loss and surviving children was limited to mothers with low education. C1 [Halland, Frode; Morken, Nils-Halvdan] Univ Bergen, Dept Global Publ Hlth & Primary Care, Bergen, Norway. [Deroo, Lisa A.] Univ Bergen, Dept Clin Sci, Bergen, Norway. [Klungsoyr, Kari] Haukeland Hosp, Dept Obstet & Gynaecol, Bergen, Norway. [Wilcox, Allen J.] Norwegian Inst Publ Hlth, Bergen, Norway. [Skjaerven, Rolv] NIEHS, Epidemiol Branch, NIH, Durham, NC USA. RP Halland, F (reprint author), Univ Bergen, Dept Global Publ Hlth & Primary Care, Bergen, Norway. EM frode.halland@gmail.com OI Wilcox, Allen/0000-0002-3376-1311 FU Norwegian Research Council, through the University of Bergen; Intramural Program of the National Institute of Environmental Health Sciences, National Institutes of Health FX This study was supported by the Norwegian Research Council, through the University of Bergen, and in part by the Intramural Program of the National Institute of Environmental Health Sciences, National Institutes of Health. NR 27 TC 1 Z9 1 U1 2 U2 2 PU BMJ PUBLISHING GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 2044-6055 J9 BMJ OPEN JI BMJ Open PY 2016 VL 6 IS 11 AR e012894 DI 10.1136/bmjopen-2016-012894 PG 8 WC Medicine, General & Internal SC General & Internal Medicine GA EG8JQ UT WOS:000391303400069 PM 27884847 ER PT J AU Noh, JW Kim, J Park, J Oh, IH Kwon, YD AF Noh, Jin-Won Kim, Jinseok Park, Jumin Oh, In-Hwan Kwon, Young Dae TI Age and gender differential relationship between employment status and body mass index among middle-aged and elderly adults: a cross-sectional study SO BMJ OPEN LA English DT Article ID NUTRITION EXAMINATION SURVEY; KOREAN NATIONAL-HEALTH; PHYSICAL-ACTIVITY; RISK-FACTORS; ALCOHOL-CONSUMPTION; METABOLIC SYNDROME; CIGARETTE-SMOKING; CHINESE ADULTS; WEIGHT-GAIN; JOB-LOSS AB Objective: To determine the influence of age and gender, respectively, on the association between employment status and body mass index (BMI) in Korean adults using a large, nationally representative sample. Design: Cross-sectional study. Setting: South Korea. Participants: 7228 from fourth wave of the Korean Longitudinal Study of Aging (KLoSA), the survey's short form and year: 'KLoSA 2012'. Main outcome measures: BMI. Results: BMI among the employed was higher than among the unemployed for those under 60. In terms of gender, employed men reported higher BMI than their unemployed counterparts, whereas employed women reported lower BMI than did unemployed women. Conclusions: Employment status showed varying impacts on obesity by age and gender. Both unemployment at or after 60, as well as unemployment among women, is associated with increased BMI compared with unemployment among younger individuals or men, respectively. C1 [Noh, Jin-Won] Eulji Univ, Dept Healthcare Management, Seongnam, South Korea. [Noh, Jin-Won] Univ Groningen, Univ Med Ctr Groningen, Groningen, Netherlands. [Kim, Jinseok] Seoul Womens Univ, Dept Social Welf, Seoul, South Korea. [Park, Jumin] NIH, Ctr Clin, Bethesda, MD 20892 USA. [Oh, In-Hwan] Kyung Hee Univ, Sch Med, Dept Prevent Med, Seoul, South Korea. [Kwon, Young Dae] Catholic Univ Korea, Coll Med, Dept Humanities & Social Med, Seoul, South Korea. [Kwon, Young Dae] Catholic Univ Korea, Catholic Inst Healthcare Management, Seoul, South Korea. RP Kwon, YD (reprint author), Catholic Univ Korea, Coll Med, Dept Humanities & Social Med, Seoul, South Korea.; Kwon, YD (reprint author), Catholic Univ Korea, Catholic Inst Healthcare Management, Seoul, South Korea. EM snukyd1@naver.com OI Kwon, Young Dae/0000-0002-8781-6832 NR 38 TC 0 Z9 0 U1 2 U2 2 PU BMJ PUBLISHING GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 2044-6055 J9 BMJ OPEN JI BMJ Open PY 2016 VL 6 IS 11 AR e012117 DI 10.1136/bmjopen-2016-012117 PG 6 WC Medicine, General & Internal SC General & Internal Medicine GA EG8JQ UT WOS:000391303400144 PM 27852710 ER PT J AU Tollanes, MC Strandberg-Larsen, K Forthun, I Petersen, TG Moster, D Andersen, AMN Stoltenberg, C Olsen, J Wilcox, AJ AF Tollanes, Mette C. Strandberg-Larsen, Katrine Forthun, Ingeborg Petersen, Tanja Gram Moster, Dag Andersen, Anne-Marie Nybo Stoltenberg, Camilla Olsen, Jorn Wilcox, Allen J. TI Cohort profile: cerebral palsy in the Norwegian and Danish birth cohorts (MOBAND-CP) SO BMJ OPEN LA English DT Article ID CHILD COHORT; PREGNANCY; REGISTRY; MOTHER; RISK; NORWAY AB Purpose: The purpose of MOthers and BAbies in Norway and Denmark cerebral palsy (MOBAND-CP) was to study CP aetiology in a prospective design. Participants: MOBAND-CP is a cohort of more than 210 000 children, created as a collaboration between the world's two largest pregnancy cohorts-the Norwegian Mother and Child Cohort study (MoBa) and the Danish National Birth Cohort. MOBAND-CP includes maternal interview/questionnaire data collected during pregnancy and follow-up, plus linked information from national health registries. Findings to date: Initial harmonisation of data from the 2 cohorts has created 140 variables for children and their mothers. In the MOBAND-CP cohort, 438 children with CP have been identified through record linkage with validated national registries, providing by far the largest such sample with prospectively collected detailed pregnancy data. Several studies investigating various hypotheses regarding CP aetiology are currently on-going. Future plans: Additional data can be harmonised as necessary to meet requirements of new projects. Biological specimens collected during pregnancy and at delivery are potentially available for assay, as are results from assays conducted on these specimens for other projects. The study size allows consideration of CP subtypes, which is rare in aetiological studies of CP. In addition, MOBAND-CP provides a platform within the context of a merged birth cohort of exceptional size that could, after appropriate permissions have been sought, be used for cohort and case-cohort studies of other relatively rare health conditions of infants and children. C1 [Tollanes, Mette C.; Forthun, Ingeborg; Moster, Dag; Stoltenberg, Camilla] Univ Bergen, Dept Global Publ Hlth & Primary Care, Bergen, Norway. [Tollanes, Mette C.; Forthun, Ingeborg; Moster, Dag] Norwegian Inst Publ Hlth, Domain Hlth Data & Digitalizat, Bergen, Norway. [Strandberg-Larsen, Katrine; Petersen, Tanja Gram; Andersen, Anne-Marie Nybo] Univ Copenhagen, Dept Publ Hlth, Copenhagen, Denmark. [Forthun, Ingeborg; Moster, Dag] Haukeland Hosp, Dept Paediat, Bergen, Norway. [Stoltenberg, Camilla] Norwegian Inst Publ Hlth, Oslo, Norway. [Olsen, Jorn] Aarhus Univ, Inst Publ Hlth, Aarhus, Denmark. [Olsen, Jorn] Univ Calif Los Angeles, Fielding Sch Publ Hlth, Los Angeles, CA USA. [Wilcox, Allen J.] NIEHS, Durham, NC USA. RP Tollanes, MC (reprint author), Univ Bergen, Dept Global Publ Hlth & Primary Care, Bergen, Norway.; Tollanes, MC (reprint author), Norwegian Inst Publ Hlth, Domain Hlth Data & Digitalizat, Bergen, Norway. EM Mette.tollanes@uib.no OI Wilcox, Allen/0000-0002-3376-1311 FU National Institute for Environmental Health Sciences (NIEHS/NIH) FX This research has been supported in part by the Intramural Program of the National Institute for Environmental Health Sciences (NIEHS/NIH). NR 29 TC 0 Z9 0 U1 0 U2 0 PU BMJ PUBLISHING GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 2044-6055 J9 BMJ OPEN JI BMJ Open PY 2016 VL 6 IS 9 AR e012777 DI 10.1136/bmjopen-2016-012777 PG 5 WC Medicine, General & Internal SC General & Internal Medicine GA EG8JL UT WOS:000391302900181 ER PT J AU Case, LK Ceko, M Gracely, JL Richards, EA Olausson, H Bushnell, MC AF Case, Laura K. Ceko, Marta Gracely, John L. Richards, Emily A. Olausson, Hakan Bushnell, M. Catherine TI Touch Perception Altered by Chronic Pain and by Opioid Blockade SO ENEURO LA English DT Article DE affective touch; C-tactile fibers; chronic pain; fibromyalgia; opioids; somatosensation ID FIBROMYALGIA IMPACT QUESTIONNAIRE; UNMYELINATED TACTILE AFFERENTS; POSITRON-EMISSION-TOMOGRAPHY; HUMAN HAIRY SKIN; RECEPTOR-BINDING; RHEUMATOID-ARTHRITIS; NEUROPATHIC PAIN; CINGULATE GYRUS; SOCIAL-BEHAVIOR; MONKEYS AB Touch plays a significant role in human social behavior and social communication, and its rewarding nature has been suggested to involve opioids. Opioid blockade in monkeys leads to increased solicitation and receipt of grooming, suggesting heightened enjoyment of touch. We sought to study the role of endogenous opioids in perception of affective touch in healthy adults and in patients with fibromyalgia, a chronic pain condition shown to involve reduced opioid receptor availability. The pleasantness of touch has been linked to the activation of C-tactile fibers, which respond maximally to slow gentle touch and correlate with ratings of pleasantness. We administered naloxone to patients and healthy controls to directly observe the consequences of similar to -opioid blockade on the perceived pleasantness and intensity of touch. We found that at baseline chronic pain patients showed a blunted distinction between slow and fast brushing for both intensity and pleasantness, suggesting reduced C-tactile touch processing. In addition, we found a differential effect of opioid blockade on touch perception in healthy subjects and pain patients. In healthy individuals, opioid blockade showed a trend toward increased ratings of touch pleasantness, while in chronic pain patients it significantly decreased ratings of touch intensity. Further, in healthy individuals, naloxone-induced increase in touch pleasantness was associated with naloxone-induced decreased preference for slow touch, suggesting a possible effect of opioid levels on processing of C-tactile fiber input. These findings suggest a role for endogenous opioids in touch processing, and provide further evidence for altered opioid functioning in chronic pain patients. C1 [Case, Laura K.; Ceko, Marta; Gracely, John L.; Richards, Emily A.; Bushnell, M. Catherine] NIH, Natl Ctr Complementary & Integrat Hlth, Bldg 10,CRC RM 4-1730 MSC 1302, Bethesda, MD 20892 USA. [Olausson, Hakan] Linkoping Univ, Ctr Social & Affect Neurosci, Dept Clin & Expt Med, S-58183 Linkoping, Sweden. RP Case, LK (reprint author), NIH, Natl Ctr Complementary & Integrat Hlth, Bldg 10,CRC RM 4-1730 MSC 1302, Bethesda, MD 20892 USA. EM laura.case@nih.gov FU Division of Intramural Research, National Center for Complementary and Integrative Health, National Institutes of Health, Bethesda, Maryland FX This work was supported by the Division of Intramural Research, National Center for Complementary and Integrative Health, National Institutes of Health, Bethesda, Maryland. We thank Petra Schweinhardt for her invaluable comments on a previous draft of this paper. NR 50 TC 1 Z9 1 U1 2 U2 2 PU SOC NEUROSCIENCE PI WASHINGTON PA 11 DUPONT CIRCLE, NW, STE 500, WASHINGTON, DC 20036 USA SN 2373-2822 J9 ENEURO JI eNeuro PD JAN-FEB PY 2016 VL 3 IS 1 DI 10.1523/ENEURO.0138-15.2016 PG 10 WC Neurosciences SC Neurosciences & Neurology GA EH7AS UT WOS:000391925700018 ER PT J AU Liu, X Lin, YJ Cheng, Y AF Liu, Xiang Lin, Ying-Ju Cheng, Yong TI Complementary and Alternative Therapies for Inflammatory Diseases SO EVIDENCE-BASED COMPLEMENTARY AND ALTERNATIVE MEDICINE LA English DT Editorial Material C1 [Liu, Xiang; Cheng, Yong] NIH, Bethesda, MD 20892 USA. [Lin, Ying-Ju] China Med Univ, Taichung 40402, Taiwan. RP Liu, X (reprint author), NIH, Bethesda, MD 20892 USA. EM xiang.liu@nih.gov OI Cheng, Yong/0000-0002-7529-4408 NR 0 TC 0 Z9 0 U1 0 U2 0 PU HINDAWI PUBLISHING CORP PI NEW YORK PA 315 MADISON AVE 3RD FLR, STE 3070, NEW YORK, NY 10017 USA SN 1741-427X EI 1741-4288 J9 EVID-BASED COMPL ALT JI Evid.-based Complement Altern. Med. PY 2016 AR 8324815 DI 10.1155/2016/8324815 PG 2 WC Integrative & Complementary Medicine SC Integrative & Complementary Medicine GA EH8GW UT WOS:000392011000001 ER PT J AU Huang, P Ling, DS Song, JB Liu, G Xie, J AF Huang, Peng Ling, Daishun Song, Jibin Liu, Gang Xie, Jin TI Nanomaterials for Cancer Phototheranostics SO JOURNAL OF NANOMATERIALS LA English DT Editorial Material C1 [Huang, Peng] Shenzhen Univ, Sch Biomed Engn, Guangdong Key Lab Biomed Measurements & Ultrasoun, Shenzhen 518060, Peoples R China. [Ling, Daishun] Zhejiang Univ, Coll Pharmaceut Sci, Inst Pharmaceut, Hangzhou 310058, Zhejiang, Peoples R China. [Song, Jibin] NIBIB, Lab Mol Imaging & Nanomed, NIH, Bethesda, MD 20892 USA. [Liu, Gang] Xiamen Univ, Sch Publ Hlth, Ctr Mol Imaging & Translat Med, Xiamen 361102, Peoples R China. [Xie, Jin] Univ Georgia, Dept Chem, Bioimaging Res Ctr, Athens, GA 30602 USA. RP Huang, P (reprint author), Shenzhen Univ, Sch Biomed Engn, Guangdong Key Lab Biomed Measurements & Ultrasoun, Shenzhen 518060, Peoples R China. EM peng.huang@szu.edu.cn RI Ling, Daishun/J-4736-2014 OI Ling, Daishun/0000-0002-6814-7370 NR 0 TC 0 Z9 0 U1 3 U2 3 PU HINDAWI PUBLISHING CORP PI NEW YORK PA 315 MADISON AVE 3RD FLR, STE 3070, NEW YORK, NY 10017 USA SN 1687-4110 EI 1687-4129 J9 J NANOMATER JI J. Nanomater. PY 2016 AR 4053976 DI 10.1155/2016/4053976 PG 2 WC Nanoscience & Nanotechnology; Materials Science, Multidisciplinary SC Science & Technology - Other Topics; Materials Science GA EH8EH UT WOS:000392004100001 ER PT J AU Manoharan, S Guillemin, GJ Abiramasundari, RS Essa, MM Akbar, M Akbar, MD AF Manoharan, Shanmugam Guillemin, Gilles J. Abiramasundari, Rajagopal Selladurai Essa, Musthafa Mohamed Akbar, Mohammed Akbar, Mohammed D. TI The Role of Reactive Oxygen Species in the Pathogenesis of Alzheimer's Disease, Parkinson's Disease, and Huntington's Disease: A Mini Review SO OXIDATIVE MEDICINE AND CELLULAR LONGEVITY LA English DT Review ID INDUCED OXIDATIVE STRESS; AMYLOID-BETA-PEPTIDE; PROTECTS DOPAMINERGIC-NEURONS; TRANSGENIC DROSOPHILA MODEL; ANTIOXIDANT ENZYME-ACTIVITY; MILD COGNITIVE IMPAIRMENT; SOMNIFERA ROOT EXTRACT; NIGRA PARS COMPACTA; REDOX-ACTIVE IRON; SUBSTANTIA-NIGRA AB Neurodegenerative diseases affect not only the life quality of aging populations, but also their life spans. All forms of neurodegenerative diseases have a massive impact on the elderly. The major threat of these brain diseases includes progressive loss of memory, Alzheimer's disease (AD), impairments in the movement, Parkinson's disease (PD), and the inability to walk, talk, and think, Huntington's disease (HD). Oxidative stress and mitochondrial dysfunction are highlighted as a central feature of brain degenerative diseases. Oxidative stress, a condition that occurs due to imbalance in oxidant and antioxidant status, has been known to play a vital role in the pathophysiology of neurodegenerative diseases including AD, PD, and HD. A large number of studies have utilized oxidative stress biomarkers to investigate the severity of these neurodegenerative diseases and medications are available, but these only treat the symptoms. In traditional medicine, a large number of medicinal plants have been used to treat the symptoms of these neurodegenerative diseases. Extensive studies scientifically validated the beneficial effect of natural products against neurodegenerative diseases using suitable animal models. This short review focuses the role of oxidative stress in the pathogenesis of AD, PD, and HD and the protective efficacy of natural products against these diseases. C1 [Manoharan, Shanmugam; Abiramasundari, Rajagopal Selladurai] Annamalai Univ, Dept Biochem & Biotechnol, Fac Sci, Annamalainagar, Tamil Nadu, India. [Guillemin, Gilles J.] Macquarie Univ, Dept Biomed Res, Neuroinflammat Grp, Fac Med & Hlth Sci, Sydney, NSW, Australia. [Essa, Musthafa Mohamed] Sultan Qaboos Univ, Dept Food Sci & Nutr, Muscat, Oman. [Akbar, Mohammed; Akbar, Mohammed D.] NIAAA, SMPT, NIH, Rockville, MD 20852 USA. RP Guillemin, GJ (reprint author), Macquarie Univ, Dept Biomed Res, Neuroinflammat Grp, Fac Med & Hlth Sci, Sydney, NSW, Australia. EM gilles.guillemin@mq.edu.au OI Guillemin, Gilles/0000-0001-8105-4470 NR 203 TC 1 Z9 1 U1 6 U2 6 PU HINDAWI PUBLISHING CORP PI NEW YORK PA 315 MADISON AVE 3RD FLR, STE 3070, NEW YORK, NY 10017 USA SN 1942-0900 EI 1942-0994 J9 OXID MED CELL LONGEV JI Oxidative Med. Cell. Longev. PY 2016 AR 8590578 DI 10.1155/2016/8590578 PG 15 WC Cell Biology SC Cell Biology GA EH9ER UT WOS:000392075000001 ER PT J AU Ferreira, JN Rungarunlert, S Urkasemsin, G Adine, C Souza, GR AF Ferreira, Joao N. Rungarunlert, Sasitorn Urkasemsin, Ganokon Adine, Christabella Souza, Glauco R. TI Three-Dimensional Bioprinting Nanotechnologies towards Clinical Application of Stem Cells and Their Secretome in Salivary Gland Regeneration SO STEM CELLS INTERNATIONAL LA English DT Review ID AMNIOTIC EPITHELIAL-CELLS; PREVENTS RADIATION-DAMAGE; FIBROBLAST-GROWTH-FACTOR; MARROW-DERIVED CELLS; MAGNETIC-LEVITATION; BRANCHING MORPHOGENESIS; COCULTURE MODEL; TRANSIENT ACTIVATION; ACINAR-CELLS; IN-VITRO AB Salivary gland (SG) functional damage and severe dry mouth (or xerostomia) are commonly observed in a wide range of medical conditions from autoimmune tometabolic disorders as well as after radiotherapy to treat specific head and neck cancers. No effective therapy has been developed to completely restore the SG functional damage on the long-term and reverse the poor quality of life of xerostomia patients. Cell-and secretome-based strategies are currently being tested in vitro and in vivo for the repair and/or regeneration of the damaged SG using (1) epithelial SG stem/progenitor cells from salispheres or explant cultures as well as (2) nonepithelial stem cell types and/or their bioactive secretome. These strategies will be the focus of our review. Herein, innovative 3D bioprinting nanotechnologies for the generation of organotypic (-cultures and SG organoids/mini-glands will also be discussed. These bioprinting technologies will allow researchers to analyze the secretome components and extracellular matrix production, as well as their biofunctional effects in 3D mini-glands ex vivo. Improving our understanding of the SG secretome is critical to develop effective secretome-based therapies towards the regeneration and/or repair of all SG compartments for proper restoration of saliva secretion and flow into the oral cavity. C1 [Ferreira, Joao N.; Adine, Christabella] Natl Univ Singapore, Dept Oral & Maxillofacial Surg, Fac Dent, Singapore, Singapore. [Ferreira, Joao N.] Natl Inst Dent & Craniofacial Res, NIH, Bethesda, MD 20892 USA. [Rungarunlert, Sasitorn; Urkasemsin, Ganokon] Mahidol Univ, Dept Preclin & Appl Anim Sci, Fac Vet Sci, Nakhon Pathom, Thailand. [Souza, Glauco R.] Univ Texas Hlth Sci Ctr Houston, Houston, TX 77030 USA. [Souza, Glauco R.] Nano3D Biosci N3D, Houston, TX USA. RP Ferreira, JN (reprint author), Natl Univ Singapore, Dept Oral & Maxillofacial Surg, Fac Dent, Singapore, Singapore.; Ferreira, JN (reprint author), Natl Inst Dent & Craniofacial Res, NIH, Bethesda, MD 20892 USA. EM denjnarf@nus.edu.sg FU National University of Singapore ODPRT start up grant [R-221-000-072-133]; Singapore's National Medical Research Council [CNIG14NOV008]; Mahidol University FX Our research studies are currently funded by the National University of Singapore ODPRT start up grant (R-221-000-072-133), by the Singapore's National Medical Research Council grant (CNIG14NOV008), and by Mahidol University. NR 76 TC 0 Z9 0 U1 2 U2 2 PU HINDAWI PUBLISHING CORP PI NEW YORK PA 315 MADISON AVE 3RD FLR, STE 3070, NEW YORK, NY 10017 USA SN 1687-966X EI 1687-9678 J9 STEM CELLS INT JI Stem Cells Int. PY 2016 AR 7564689 DI 10.1155/2016/7564689 PG 9 WC Cell & Tissue Engineering SC Cell Biology GA EH4AV UT WOS:000391714200001 ER PT J AU Gregory, S Iles-Caven, Y Hibbeln, JR Taylor, CM Golding, J AF Gregory, Steve Iles-Caven, Yasmin Hibbeln, Joseph R. Taylor, Caroline M. Golding, Jean TI Are prenatal mercury levels associated with subsequent blood pressure in childhood and adolescence? The Avon prebirth cohort study SO BMJ OPEN LA English DT Article ID CORONARY HEART-DISEASE; CARDIOVASCULAR-DISEASE; METHYLMERCURY EXPOSURE; ICP-MS; PREGNANCY; CHILDREN; RISK; NUTRITION; OUTCOMES; PARENTS AB Objectives: There have been conflicting data suggesting that prenatal mercury exposure is associated with adverse cardiovascular measures in children. We therefore analysed a large prospective population study to investigate whether prenatal mercury exposure might influence offspring blood pressure (BP) and heart rate adversely. Design: Prospective birth cohort. Setting: The Avon Longitudinal Study of Parents and Children (ALSPAC). Participants: Maternal whole blood collected in the first half of pregnancy was assayed for mercury and selenium. The offspring were followed throughout childhood and adolescence. Outcome measures: Offspring resting BP and heart rates measured under standard conditions on six occasions between ages 7 and 17 years (numbers analysed: 1754 at 7 years to 1102 at 17). Results: Statistical analyses took account of various factors present in pregnancy, including family adversity, maternal age, parity, smoking and alcohol intake. Unadjusted and adjusted regression analyses assessed the relationship between maternal prenatal mercury levels and offspring resting systolic and diastolic BP, and heart rates. A final set of analyses took account of selenium. Each analysis was carried out for all offspring, those whose mothers had, and those that had not, consumed fish during pregnancy. Further analysis for all offspring ascertained whether there were significant interaction effects between the sexes. There was little evidence to suggest that prenatal mercury exposure resulted in a clinically important increase in offspring BP in the whole group, since no effect size for an increase of 1 SD of blood mercury level was >0.3 mm Hg. Only 1 association was significant at p<0.05 and therefore likely due to chance. Conclusions: This study reveals no evidence to support the hypothesis that prenatal mercury exposure has adverse long-term effects on offspring BP or heart rates during childhood or adolescence. C1 [Gregory, Steve; Iles-Caven, Yasmin; Taylor, Caroline M.; Golding, Jean] Univ Bristol, Sch Social & Community Med, Ctr Child & Adolescent Hlth, Bristol, Avon, England. [Hibbeln, Joseph R.] NIAAA, Dept Nutr Neurosci, LMBB, NIH, Bethesda, MD USA. RP Golding, J (reprint author), Univ Bristol, Sch Social & Community Med, Ctr Child & Adolescent Hlth, Bristol, Avon, England. EM jean.golding@bristol.ac.uk OI Golding, Jean/0000-0003-2826-3307 FU UK Medical Research Council; Wellcome Trust [102215/2/13/2]; University of Bristol; National Oceanic and Atmospheric Administration (NOAA); NOAA; Intramural Research Program of the National Institutes Alcohol Abuse & Alcoholism (NIAAA), NIH; Wellcome Trust Career Re-Entry Fellowship [104077/Z/14/Z] FX The UK Medical Research Council and the Wellcome Trust (Grant ref: 102215/2/13/2) and the University of Bristol currently provide core support for ALSPAC. The assays of the maternal blood samples were carried out at the Centers for Disease Control and Prevention with funding from National Oceanic and Atmospheric Administration (NOAA), and the statistical analyses were carried out with funding from NOAA and support from the Intramural Research Program of the National Institutes Alcohol Abuse & Alcoholism (NIAAA), NIH. CMT was supported by a Wellcome Trust Career Re-Entry Fellowship (Grant ref: 104077/Z/14/Z). This research received no specific grant from any funding agency in the public, commercial or not-for-profit sectors. NR 25 TC 0 Z9 0 U1 2 U2 2 PU BMJ PUBLISHING GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 2044-6055 J9 BMJ OPEN JI BMJ Open PY 2016 VL 6 IS 10 AR e012425 DI 10.1136/bmjopen-2016-012425 PG 8 WC Medicine, General & Internal SC General & Internal Medicine GA EG8JO UT WOS:000391303200053 PM 27742626 ER PT J AU Mbuagbaw, L Mursleen, S Irlam, JH Spaulding, AB Rutherford, GW Siegfried, N AF Mbuagbaw, Lawrence Mursleen, Sara Irlam, James H. Spaulding, Alicen B. Rutherford, George W. Siegfried, Nandi TI Efavirenz or nevirapine in three-drug combination therapy with two nucleoside or nucleotide-reverse transcriptase inhibitors for initial treatment of HIV infection in antiretroviral-naive individuals SO COCHRANE DATABASE OF SYSTEMATIC REVIEWS LA English DT Review DE Anti-HIV Agents [therapeutic use]; Benzoxazines [adverse effects; therapeutic use]; Drug Therapy,Combination [methods]; HIV Infections [drug therapy; mortality]; Nevirapine [adverse effects; therapeutic use]; Randomized Controlled Trials as Topic; Reverse Transcriptase Inhibitors [adverse effects; therapeutic use]; Adult; Humans ID ONCE-DAILY NEVIRAPINE; OPEN-LABEL; PROTEASE INHIBITOR; CONTAINING REGIMENS; LIVER TOXICITY; THAI HIV; TUBERCULOSIS; TRIAL; EFFICACY; SAFETY AB Background The advent of highly active antiretroviral therapy (ART) has reduced the morbidity and mortality due to HIV infection. The World Health Organization (WHO) ART guidelines focus on three classes of antiretroviral drugs, namely nucleoside or nucleotide reverse transcriptase inhibitors (NRTI), non-nucleoside reverse transcriptase inhibitors (NNRTI) and protease inhibitors. Two of the most common medications given as first-line treatment are the NNRTIs, efavirenz (EFV) and nevirapine (NVP). It is unclear which NNRTI is more efficacious for initial therapy. This systematic review was first published in 2010. Objectives To determine which non-nucleoside reverse transcriptase inhibitor, either EFV or NVP, is more effective in suppressing viral load when given in combination with two nucleoside reverse transcriptase inhibitors as part of initial antiretroviral therapy for HIV infection in adults and children. Search methods We attempted to identify all relevant studies, regardless of language or publication status, in electronic databases and conference proceedings up to 12 August 2016. We searched MEDLINE, Embase, the Cochrane Central Register of Controlled Trials (CENTRAL), the World Health Organization (WHO) International Clinical Trials Registry Platform (ICTRP) and ClinicalTrials.gov to 12 August 2016. We searched LILACS (Latin American and Caribbean Health Sciences Literature) and the Web of Science from 1996 to 12 August 2016. We checked the National Library of Medicine (NLM) Gateway from 1996 to 2009, as it was no longer available after 2009. Selection criteria We included all randomized controlled trials (RCTs) that compared EFV to NVP in people with HIV without prior exposure to ART, irrespective of the dosage or NRTI's given in combination. The primary outcome of interest was virological success. Other primary outcomes included mortality, clinical progression to AIDS, severe adverse events, and discontinuation of therapy for any reason. Secondary outcomes were change in CD4 count, treatment failure, development of ART drug resistance, and prevention of sexual transmission of HIV. Data collection and analysis Two review authors assessed each reference for inclusion using exclusion criteria that we had established a priori. Two review authors independently extracted data from each included trial using a standardized data extraction form. We analysed data on an intention-to-treat basis. We performed subgroup analyses for concurrent treatment for tuberculosis and dosage of NVP. We followed standard Cochrane methodological procedures. Main results Twelve RCTs, which included 3278 participants, met our inclusion criteria. None of these trials included children. The length of follow-up time, study settings, and NRTI combination drugs varied greatly. In five included trials, participants were receiving concurrent treatment for tuberculosis. There was little or no difference between EFV and NVP in virological success (RR 1.04, 95% CI 0.99 to 1.09; 10 trials, 2438 participants; high quality evidence), probably little or no difference in mortality (RR 0.84, 95% CI 0.59 to 1.19; 8 trials, 2317 participants; moderate quality evidence) and progression to AIDS (RR 1.23, 95% CI 0.72 to 2.11; 5 trials, 2005 participants; moderate quality evidence). We are uncertain whether there is a difference in all severe adverse events (RR 0.91, 95% CI 0.71 to 1.18; 8 trials, 2329 participants; very low quality evidence). There is probably little or no difference in discontinuation rate (RR 0.93, 95% CI 0.69 to 1.25; 9 trials, 2384 participants; moderate quality evidence) and change in CD4 count (MD -3.03; 95% CI -17.41 to 11.35; 9 trials, 1829 participants; moderate quality evidence). There may be little or no difference in treatment failure (RR 0.97, 95% CI 0.76 to 1.24; 5 trials, 737 participants; low quality evidence). Development of drug resistance is probably slightly less in the EFV arms (RR 0.76, 95% CI 0.60 to 0.95; 4 trials, 988 participants; moderate quality evidence). No studies were found that looked at sexual transmission of HIV. When we examined the adverse events individually, EFV probably is associated with more people with impaired mental function (7 per 1000) compared to NVP (2 per 1000; RR 4.46, 95% CI 1.65 to 12.03; 6 trials, 2049 participants; moderate quality evidence) but fewer people with elevated transaminases (RR 0.52, 95% CI 0.35 to 0.78; 3 trials, 1299 participants; high quality evidence), fewer people with neutropenia (RR 0.48, 95% CI 0.28 to 0.82; 3 trials, 1799 participants; high quality evidence), and probably fewer people with rash (229 per 100 with NVP versus 133 per 1000 with EFV; RR 0.58, 95% CI 0.34 to 1.00; 7 trials, 2277 participants; moderate quality evidence). We found that there may be little or no difference in gastrointestinal adverse events (RR 0.76, 95% CI 0.48 to 1.21; 6 trials, 2049 participants; low quality evidence), pyrexia (RR 0.65, 95% CI 0.15 to 2.73; 3 trials, 1799 participants; low quality evidence), raised alkaline phosphatase (RR 0.65, 95% CI 0.17 to 2.50; 1 trial, 1007 participants; low quality evidence), raised amylase (RR 1.40, 95% CI 0.72 to 2.73; 2 trials, 1071 participants; low quality evidence) and raised triglycerides (RR 1.10, 95% CI 0.39 to 3.13; 2 trials, 1071 participants; low quality evidence). There was probably little or no difference in serum glutamic oxaloacetic transaminase (SGOT; MD 3.3, 95% CI -2.06 to 8.66; 1 trial, 135 participants; moderate quality evidence), serum glutamic-pyruvic transaminase (SGPT; MD 5.7, 95% CI -4.23 to 15.63; 1 trial, 135 participants; moderate quality evidence) and raised cholesterol (RR 6.03, 95% CI 0.75 to 48.78; 1 trial, 64 participants; moderate quality evidence). Our subgroup analyses revealed that NVP slightly increases mortality when given once daily (RR 0.34, 95% CI 0.13 to 0.90; 3 trials, 678 participants; high quality evidence). There were little or no differences in the primary outcomes for patients who were concurrently receiving treatment for tuberculosis. Authors' conclusions Both drugs have similar benefits in initial treatment of HIV infection when combined with two NRTIs. The adverse events encountered affect different systems, with EFV more likely to cause central nervous system adverse events and NVP more likely to raise transaminases, cause neutropenia and rash. C1 [Mbuagbaw, Lawrence] Yaounde Cent Hosp, CDBPH, Henri Dunant Ave,POB 87, Yaounde, Cameroon. [Mbuagbaw, Lawrence; Mursleen, Sara] McMaster Univ, Dept Clin Epidemiol & Biostat, Hamilton, ON, Canada. [Irlam, James H.] Univ Cape Town, Primary Hlth Care Directorate, Cape Town, South Africa. [Spaulding, Alicen B.] NIAID, Lab Clin Infect Dis, 9000 Rockville Pike, Bethesda, MD 20892 USA. [Rutherford, George W.] Univ Calif San Francisco, Global Hlth Sci, San Francisco, CA 94143 USA. [Siegfried, Nandi] MRC, Alcohol Tobacco & Other Drug Res Unit, Tygerberg, South Africa. RP Mbuagbaw, L (reprint author), Yaounde Cent Hosp, CDBPH, Henri Dunant Ave,POB 87, Yaounde, Cameroon. EM mbuagblc@mcmaster.ca FU South African Cochrane Centre, Medical Research Council, South Africa; Cochrane HIV/AIDS Mentoring Programme, South Africa; Liverpool School of Tropical Medicine, UK; Centers for Disease Control and Prevention (CDC), USA [U2GPS001468]; World Health Organization (WHO), Switzerland [200106621]; Department for International Development, UK [5242] FX Internal sources; South African Cochrane Centre, Medical Research Council, South Africa.; Cochrane HIV/AIDS Mentoring Programme, South Africa.; Liverpool School of Tropical Medicine, UK.; External sources; Centers for Disease Control and Prevention (CDC), USA.; Cooperative Agreement #U2GPS001468 "Atlanta HQ UCSF Technical Assistance to Support the President's Emergency Plan for AIDS Relief " from the CDC, with funds from the National Center for HIV, Viral Hepatitis, STDs and TB Prevention (NCHSTP). Its contents are solely the responsibility of the review authors and do not necessarily represent the official views of the CDC.; World Health Organization (WHO), Switzerland.; WHO #200106621, Systematic reviews and development of GRADE profiles, based on the new WHO GRC guidelines, for the "WHO Guidelines on antiretroviral therapy for HIV infection in adults and adolescents - 2009 revision."; Department for International Development, UK.; Grant: 5242 NR 68 TC 0 Z9 0 U1 2 U2 2 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1469-493X EI 1361-6137 J9 COCHRANE DB SYST REV JI Cochrane Database Syst Rev. PY 2016 IS 12 AR CD004246 DI 10.1002/14651858.CD004246.pub4 PG 97 WC Medicine, General & Internal SC General & Internal Medicine GA EG8OU UT WOS:000391317400010 ER PT J AU Walitt, B Klose, P Fitzcharles, MA Phillips, T Hauser, W AF Walitt, Brian Klose, Petra Fitzcharles, Mary-Ann Phillips, Tudor Haeuser, Winfried TI Cannabinoids for fibromyalgia SO COCHRANE DATABASE OF SYSTEMATIC REVIEWS LA English DT Review ID INDIVIDUAL PATIENT DATA; CHRONIC PAIN; ENDOCANNABINOID SYSTEM; TREATMENT OUTCOMES; RESPONDER ANALYSIS; RANDOMIZED-TRIALS; LONGITUDINAL DATA; STRESS-DISORDER; CLINICAL-TRIALS; MARIJUANA USE AB Background This review is one of a series on drugs used to treat fibromyalgia. Fibromyalgia is a clinically well-defined chronic condition of unknown aetiology characterised by chronic widespread pain that often co-exists with sleep problems and fatigue affecting approximately 2% of the general population. People often report high disability levels and poor health-related quality of life (HRQoL). Drug therapy focuses on reducing key symptoms and disability, and improving HRQoL. Cannabis has been used for millennia to reduce pain and other somatic and psychological symptoms. Objectives To assess the efficacy, tolerability and safety of cannabinoids for fibromyalgia symptoms in adults. Search methods We searched the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE and EMBASE to April 2016, together with reference lists of retrieved papers and reviews, three clinical trial registries, and contact with trial authors. Selection criteria We selected randomised controlled trials of at least four weeks' duration of any formulation of cannabis products used for the treatment of adults with fibromyalgia. Data collection and analysis Two review authors independently extracted the data of all included studies and assessed risk of bias. We resolved discrepancies by discussion. We performed analysis using three tiers of evidence. First tier evidence was derived from data meeting current best standards and subject to minimal risk of bias (outcome equivalent to substantial pain intensity reduction, intention-to-treat analysis without imputation for drop-outs; at least 200 participants in the comparison, eight to 12 weeks' duration, parallel design), second tier evidence from data that did not meet one or more of these criteria and were considered at some risk of bias but with adequate numbers (i.e. data from at least 200 participants) in the comparison, and third tier evidence from data involving small numbers of participants that were considered very likely to be biased or used outcomes of limited clinical utility, or both. We assessed the evidence using GRADE (Grading of Recommendations Assessment, Development and Evaluation). Main results We included two studies with 72 participants. Overall, the two studies were at moderate risk of bias. The evidence was derived from group mean data and completer analysis (very low quality evidence overall). We rated the quality of all outcomes according to GRADE as very low due to indirectness, imprecision and potential reporting bias. The primary outcomes in our review were participant-reported pain relief of 50% or greater, Patient Global Impression of Change (PGIC) much or very much improved, withdrawal due to adverse events (tolerability) and serious adverse events (safety). Nabilone was compared to placebo and to amitriptyline in one study each. Study sizes were 32 and 40 participants. One study used a cross-over design and one used a parallel group design; study duration was four or six weeks. Both studies used nabilone, a synthetic cannabinoid, with a bedtime dosage of 1 mg/day. No study reported the proportion of participants experiencing at least 30% or 50% pain relief or who were very much improved. No study provided first or second tier (high to moderate quality) evidence for an outcome of efficacy, tolerability and safety. Third tier (very low quality) evidence indicated greater reduction of pain and limitations of HRQoL compared to placebo in one study. There were no significant differences to placebo noted for fatigue and depression (very low quality evidence). Third tier evidence indicated better effects of nabilone on sleep than amitriptyline (very low quality evidence). There were no significant differences between the two drugs noted for pain, mood and HRQoL (very low quality evidence). More participants dropped out due to adverse events in the nabilone groups (4/52 participants) than in the control groups (1/20 in placebo and 0/32 in amitriptyline group). The most frequent adverse events were dizziness, nausea, dry mouth and drowsiness (six participants with nabilone). Neither study reported serious adverse events during the period of both studies. We planned to create a GRADE 'Summary of findings' table, but due to the scarcity of data we were unable to do this. We found no relevant study with herbal cannabis, plant-based cannabinoids or synthetic cannabinoids other than nabilone in fibromyalgia. Authors' conclusions We found no convincing, unbiased, high quality evidence suggesting that nabilone is of value in treating people with fibromyalgia. The tolerability of nabilone was low in people with fibromyalgia. C1 [Walitt, Brian] NIH, Natl Ctr Complementary & Integrat Hlth, Bldg 10, Bethesda, MD 20892 USA. [Walitt, Brian] NINR, NIH, Bethesda, MD 20892 USA. [Klose, Petra] Univ Duisburg Essen, Kliniken Essen Mitte, Fac Med, Dept Internal & Integrat Med, Essen, Germany. [Fitzcharles, Mary-Ann] McGill Univ, Ctr Hlth, Montreal Gen Hosp, Div Rheumatol, Montreal, PQ, Canada. [Phillips, Tudor] Univ Oxford, Pain Res, Oxford, England. [Phillips, Tudor] Univ Oxford, Nuffield Dept Clin Neurosci, Nuffield Div Anaesthet, Oxford, England. [Haeuser, Winfried] Tech Univ Munich, Dept Psychosomat Med & Psychotherapy, Langerstr 3, D-81675 Munich, Germany. RP Hauser, W (reprint author), Tech Univ Munich, Dept Psychosomat Med & Psychotherapy, Langerstr 3, D-81675 Munich, Germany. EM whaeuser@klinikum-saarbruecken.de OI Klose, Petra/0000-0001-9319-2491 FU Ruth und Kurt Bahlsen Stiftung, Germany; Ruth und Kurt Bahlsen Stiftung; National Center for Complementary and Integrative Health, USA; Intramural Research Program of the National Institutes of Health, National Center for Complementary and Integrative Health FX External sources; Ruth und Kurt Bahlsen Stiftung, Germany.; Petra Klose was supported by the Ruth und Kurt Bahlsen Stiftung.; National Center for Complementary and Integrative Health, USA.; Brian Walitt has been supported (in part) by the Intramural Research Program of the National Institutes of Health, National Center for Complementary and Integrative Health. NR 83 TC 2 Z9 2 U1 3 U2 3 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1469-493X EI 1361-6137 J9 COCHRANE DB SYST REV JI Cochrane Database Syst Rev. PY 2016 IS 7 AR CD011694 DI 10.1002/14651858.CD011694.pub2 PG 28 WC Medicine, General & Internal SC General & Internal Medicine GA EG8EU UT WOS:000391289500024 ER PT J AU Shin, HC Lu, L Kim, L Seff, A Yao, JH Summers, RM AF Shin, Hoo-Chang Lu, Le Kim, Lauren Seff, Ari Yao, Jainhua Summers, Ronald M. TI Interleaved Text/Image Deep Mining on a Large-Scale Radiology Database for Automated Image Interpretation SO JOURNAL OF MACHINE LEARNING RESEARCH LA English DT Article DE Deep learning; Convolutional Neural Networks; Topic Models; Natural Language Processing; Medical Imaging ID MEDICAL LANGUAGE SYSTEM AB Despite tremendous progress in computer vision, there has not been an attempt to apply machine learning on very large-scale medical image databases. We present an interleaved text/image deep learning system to extract and mine the semantic interactions of radiology images and reports from a national research hospital's Picture Archiving and Communication System. With natural language processing, we mine a collection of similar to 216K representative two-dimensional images selected by clinicians for diagnostic reference and match the images with their descriptions in an automated manner. We then employ a weakly supervised approach using all of our available data to build models for generating approximate interpretations of patient images. Finally, we demonstrate a more strictly supervised approach to detect the presence and absence of a number of frequent disease types, providing more specific interpretations of patient scans. A relatively small amount of data is used for this part, due to the challenge in gathering quality labels from large raw text data. Our work shows the feasibility of large-scale learning and prediction in electronic patient records available in most modern clinical institutions. It also demonstrates the trade-offs to consider in designing machine learning systems for analyzing large medical data. C1 [Shin, Hoo-Chang; Lu, Le; Kim, Lauren; Seff, Ari; Yao, Jainhua; Summers, Ronald M.] NIH, Imaging Biomarkers & Comp Aided Diag Lab Radiol &, Ctr Clin, Bldg 10, Bethesda, MD 20892 USA. RP Shin, HC (reprint author), NIH, Imaging Biomarkers & Comp Aided Diag Lab Radiol &, Ctr Clin, Bldg 10, Bethesda, MD 20892 USA. EM HOOCHANG.SHIN@NIH.GOV; LE.LU@NIH.GOV; LAUREN.KIM2@NIH.GOV; ARI.SEFF@NIH.GOV; JYAO@CC.NIH.GOV; RMS@NIH.GOV FU Intramural Research Program of the National Institutes of Health Clinical Center; KRIBB Research Initiative Program (Korean Biomedical Scientist Fellowship Program), Korea Research Institute of Bioscience and Biotechnology, Republic of Korea FX This work was supported in part by the Intramural Research Program of the National Institutes of Health Clinical Center, and in part by a grant from the KRIBB Research Initiative Program (Korean Biomedical Scientist Fellowship Program), Korea Research Institute of Bioscience and Biotechnology, Republic of Korea. This study utilized the high-performance computational capabilities of the Biowulf Linux cluster at the National Institutes of Health, Bethesda, MD (http://biowulf.nih.gov). We thank NVIDIA for the K40 GPU donation. NR 59 TC 0 Z9 0 U1 1 U2 1 PU MICROTOME PUBL PI BROOKLINE PA 31 GIBBS ST, BROOKLINE, MA 02446 USA SN 1532-4435 J9 J MACH LEARN RES JI J. Mach. Learn. Res. PY 2016 VL 17 AR 107 PG 31 WC Automation & Control Systems; Computer Science, Artificial Intelligence SC Automation & Control Systems; Computer Science GA EH1SD UT WOS:000391546500001 ER PT S AU Villegas, M Muller, H de Herrera, AGS Schaer, R Bromuri, S Gilbert, A Piras, L Wang, JS Yan, F Ramisa, A Dellandrea, E Gaizauskas, R Mikolajczyk, K Puigcerver, J Toselli, AH Sanchez, JA Vidal, E AF Villegas, Mauricio Mueller, Henning Seco de Herrera, Alba Garcia Schaer, Roger Bromuri, Stefano Gilbert, Andrew Piras, Luca Wang, Josiah Yan, Fei Ramisa, Arnau Dellandrea, Emmanuel Gaizauskas, Robert Mikolajczyk, Krystian Puigcerver, Joan Toselli, Alejandro H. Sanchez, Joan-Andreu Vidal, Enrique BE Fuhr, N Quaresma, P Goncalves, T Larsen, B Balog, K Macdonald, C Cappellato, L Ferro, N TI General Overview of ImageCLEF at the CLEF 2016 Labs SO EXPERIMENTAL IR MEETS MULTILINGUALITY, MULTIMODALITY, AND INTERACTION, CLEF 2016 SE Lecture Notes in Computer Science LA English DT Proceedings Paper CT 7th International Conference of the CLEF-Association (CLEF) CY SEP 05-08, 2016 CL Univ Evora, Sch Sci & Technol, Comp Sci Dept, Evora, PORTUGAL SP CLEF Assoc HO Univ Evora, Sch Sci & Technol, Comp Sci Dept ID RETRIEVAL-SYSTEMS AB This paper presents an overview of the ImageCLEF 2016 evaluation campaign, an event that was organized as part of the CLEF (Conference and Labs of the Evaluation Forum) labs 2016. ImageCLEF is an ongoing initiative that promotes the evaluation of technologies for annotation, indexing and retrieval for providing information access to collections of images in various usage scenarios and domains. In 2016, the 14th edition of ImageCLEF, three main tasks were proposed: (1) identification, multi-label classification and separation of compound figures from biomedical literature; (2) automatic annotation of general web images; and (3) retrieval from collections of scanned handwritten documents. The handwritten retrieval task was the only completely novel task this year, although the other two tasks introduced several modifications to keep the proposed tasks challenging. C1 [Villegas, Mauricio; Puigcerver, Joan; Toselli, Alejandro H.; Sanchez, Joan-Andreu; Vidal, Enrique] Univ Politecn Valencia, Valencia, Spain. [Mueller, Henning; Schaer, Roger] Univ Appl Sci Western Switzerland HES SO, Sierre, Switzerland. [Seco de Herrera, Alba Garcia] Natl Lib Med, Bethesda, MD USA. [Bromuri, Stefano] Open Univ Netherlands, Heerlen, Netherlands. [Gilbert, Andrew; Yan, Fei] Univ Surrey, Guildford, Surrey, England. [Piras, Luca] Univ Cagliari, Cagliari, Italy. [Wang, Josiah; Gaizauskas, Robert] Univ Sheffield, Sheffield, S Yorkshire, England. [Ramisa, Arnau] UPC, CSIC, Inst Robot & Informat Ind, Barcelona, Spain. [Dellandrea, Emmanuel] Ecole Cent Lyon, Ecully, France. [Mikolajczyk, Krystian] Imperial Coll London, London, England. RP Villegas, M (reprint author), Univ Politecn Valencia, Valencia, Spain. EM mauvilsa@prhlt.upv.es OI Wang, Josiah/0000-0003-0048-3893 NR 38 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER INT PUBLISHING AG PI CHAM PA GEWERBESTRASSE 11, CHAM, CH-6330, SWITZERLAND SN 0302-9743 BN 978-3-319-44564-9; 978-3-319-44563-2 J9 LECT NOTES COMPUT SC PY 2016 VL 9822 BP 267 EP 285 DI 10.1007/978-3-319-44564-9_25 PG 19 WC Computer Science, Artificial Intelligence; Computer Science, Information Systems; Computer Science, Theory & Methods SC Computer Science GA BG5YM UT WOS:000389808200025 ER PT J AU Adjemian, J Frankland, TB Daida, YG Honda, JR Olivier, KN Zelazny, A Honda, S Prevots, DR AF Adjemian, J. Frankland, T. B. Daida, Y. G. Honda, J. R. Olivier, K. N. Zelazny, A. Honda, S. Prevots, D. R. TI Epidemiology Of Nontuberculous Mycobacterial Lung Disease In Hawaii SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Meeting Abstract CT International Conference of the American-Thoracic-Society (ATS) CY MAY 13-18, 2016 CL San Francisco, CA SP Amer Thorac Soc C1 [Adjemian, J.; Zelazny, A.; Prevots, D. R.] NIAID, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA. [Frankland, T. B.; Daida, Y. G.; Honda, S.] Kaiser Permanente, Honolulu, HI USA. [Honda, J. R.] Natl Jewish Hlth, Denver, CO USA. [Olivier, K. N.] NHLBI, Bldg 10, Bethesda, MD 20892 USA. EM jennifer.adjemian@nih.gov NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER THORACIC SOC PI NEW YORK PA 25 BROADWAY, 18 FL, NEW YORK, NY 10004 USA SN 1073-449X EI 1535-4970 J9 AM J RESP CRIT CARE JI Am. J. Respir. Crit. Care Med. PY 2016 VL 193 MA A3013 PG 2 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA EG0VE UT WOS:000390749602261 ER PT J AU Barochia, AV Kaler, M Cuento, R Gordon, EM Theard, P Figueroa, D Weir, N Sampson, M Remaley, AT Levine, SJ AF Barochia, A. V. Kaler, M. Cuento, R. Gordon, E. M. Theard, P. Figueroa, D. Weir, N. Sampson, M. Remaley, A. T. Levine, S. J. TI Serum High Density Lipoprotein (hdl) Cholesterol And Large Hdl Particles Are Negatively Correlated With Blood Eosinophils In Atopic Asthma SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Meeting Abstract CT International Conference of the American-Thoracic-Society (ATS) CY MAY 13-18, 2016 CL San Francisco, CA SP Amer Thorac Soc C1 [Barochia, A. V.; Kaler, M.; Cuento, R.; Gordon, E. M.; Theard, P.; Figueroa, D.; Weir, N.; Sampson, M.; Remaley, A. T.; Levine, S. J.] NIH, Bldg 10, Bethesda, MD 20892 USA. EM barochiaav@mail.nih.gov NR 0 TC 1 Z9 1 U1 0 U2 0 PU AMER THORACIC SOC PI NEW YORK PA 25 BROADWAY, 18 FL, NEW YORK, NY 10004 USA SN 1073-449X EI 1535-4970 J9 AM J RESP CRIT CARE JI Am. J. Respir. Crit. Care Med. PY 2016 VL 193 MA A1451 PG 1 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA EG0VE UT WOS:000390749600450 ER PT J AU Berdyshev, E Bronova, I Erdelyi, K Makriyannis, A Pacher, P AF Berdyshev, E. Bronova, I. Erdelyi, K. Makriyannis, A. Pacher, P. TI The Role Of Endocannabinoid System In Regulation Of Radiation-Induced Pulmonary Fibrogenesis SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Meeting Abstract CT International Conference of the American-Thoracic-Society (ATS) CY MAY 13-18, 2016 CL San Francisco, CA SP Amer Thorac Soc C1 [Berdyshev, E.; Bronova, I.] Natl Jewish Hlth, Denver, CO USA. [Erdelyi, K.; Pacher, P.] NIAAA, NIH, Bethesda, MD USA. [Makriyannis, A.] Northeastern Univ, Boston, MA 02115 USA. EM BerdyshevE@NJHealth.org NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER THORACIC SOC PI NEW YORK PA 25 BROADWAY, 18 FL, NEW YORK, NY 10004 USA SN 1073-449X EI 1535-4970 J9 AM J RESP CRIT CARE JI Am. J. Respir. Crit. Care Med. PY 2016 VL 193 MA A7839 PG 1 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA EG0VE UT WOS:000390749607772 ER PT J AU Bishai, W Ahidjo, BA Maiga, M Maiga, M Ordonez, AA Cheung, LS Beck, S Andrade, B Klunk, M Jain, S AF Bishai, W. Ahidjo, B. A. Maiga, M. Maiga, M. Ordonez, A. A. Cheung, L. S. Beck, S. Andrade, B. Klunk, M. Jain, S. TI Pirfenidone Exacerbates Granulomatous Inflammation And Disease Progression In Tuberculosis SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Meeting Abstract CT International Conference of the American-Thoracic-Society (ATS) CY MAY 13-18, 2016 CL San Francisco, CA SP Amer Thorac Soc C1 [Bishai, W.; Ahidjo, B. A.; Maiga, M.; Maiga, M.; Ordonez, A. A.; Cheung, L. S.; Beck, S.; Klunk, M.; Jain, S.] Johns Hopkins Sch Med, Baltimore, MD USA. [Andrade, B.] NIAID, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA. EM wbishai@jhmi.edu NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER THORACIC SOC PI NEW YORK PA 25 BROADWAY, 18 FL, NEW YORK, NY 10004 USA SN 1073-449X EI 1535-4970 J9 AM J RESP CRIT CARE JI Am. J. Respir. Crit. Care Med. PY 2016 VL 193 MA A2640 PG 1 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA EG0VE UT WOS:000390749601780 ER PT J AU Brass, DM Gwinn, WM Valente, A Kelly, FL Brinkley, C Nagler, A Moseley, A Morgan, DL Palmer, SM Foster, MW AF Brass, D. M. Gwinn, W. M. Valente, A. Kelly, F. L. Brinkley, C. Nagler, A. Moseley, A. Morgan, D. L. Palmer, S. M. Foster, M. W. TI Artificial Butter Flavoring Exposure Causes An Extracellular Matrix Reorganizing Proteomic Signature In Primary Human Airway Epithelial Cells SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Meeting Abstract CT International Conference of the American-Thoracic-Society (ATS) CY MAY 13-18, 2016 CL San Francisco, CA SP Amer Thorac Soc C1 [Brass, D. M.; Valente, A.; Kelly, F. L.; Brinkley, C.; Nagler, A.; Moseley, A.; Palmer, S. M.; Foster, M. W.] Duke Univ, Med Ctr, Durham, NC USA. [Gwinn, W. M.; Morgan, D. L.] NIEHS, Durham, NC USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU AMER THORACIC SOC PI NEW YORK PA 25 BROADWAY, 18 FL, NEW YORK, NY 10004 USA SN 1073-449X EI 1535-4970 J9 AM J RESP CRIT CARE JI Am. J. Respir. Crit. Care Med. PY 2016 VL 193 MA A5901 PG 1 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA EG0VE UT WOS:000390749605562 ER PT J AU Brass, DM Kelly, FL Gwinn, WM Brinkley, C Nagler, A Morgan, DL Foster, MW Palmer, SM AF Brass, D. M. Kelly, F. L. Gwinn, W. M. Brinkley, C. Nagler, A. Morgan, D. L. Foster, M. W. Palmer, S. M. TI Synthesis Of A Cross-Linked Hyaluronan Matrix By The Airway Epithelium In Experimental Bronchiolitis Obliterans SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Meeting Abstract CT International Conference of the American-Thoracic-Society (ATS) CY MAY 13-18, 2016 CL San Francisco, CA SP Amer Thorac Soc C1 [Brass, D. M.; Kelly, F. L.; Brinkley, C.; Nagler, A.; Foster, M. W.; Palmer, S. M.] Duke Univ, Med Ctr, Durham, NC USA. [Gwinn, W. M.; Morgan, D. L.] NIEHS, Durham, NC USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU AMER THORACIC SOC PI NEW YORK PA 25 BROADWAY, 18 FL, NEW YORK, NY 10004 USA SN 1073-449X EI 1535-4970 J9 AM J RESP CRIT CARE JI Am. J. Respir. Crit. Care Med. PY 2016 VL 193 MA A4117 PG 1 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA EG0VE UT WOS:000390749603500 ER PT J AU Carson, SS Cox, CE Wallenstein, S Hanson, L Danis, M Tulsky, JA Chai, E Nelson, J AF Carson, S. S. Cox, C. E. Wallenstein, S. Hanson, L. Danis, M. Tulsky, J. A. Chai, E. Nelson, J. TI A Multicenter Randomized Controlled Trial Of Palliative Care-Led Informational/emotional Support Meetings For Family Decision Makers Of Patients With Chronic Critical Illness SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Meeting Abstract CT International Conference of the American-Thoracic-Society (ATS) CY MAY 13-18, 2016 CL San Francisco, CA SP Amer Thorac Soc C1 [Carson, S. S.; Hanson, L.] Univ N Carolina, Chapel Hill, NC USA. [Cox, C. E.] Duke Univ, Med Ctr, Durham, NC USA. [Wallenstein, S.; Chai, E.] Mt Sinai Sch Med, New York, NY USA. [Danis, M.] NIH, Bldg 10, Bethesda, MD 20892 USA. [Tulsky, J. A.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Nelson, J.] Mem Sloan Kettering Canc Ctr, 1275 York Ave, New York, NY 10021 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER THORACIC SOC PI NEW YORK PA 25 BROADWAY, 18 FL, NEW YORK, NY 10004 USA SN 1073-449X EI 1535-4970 J9 AM J RESP CRIT CARE JI Am. J. Respir. Crit. Care Med. PY 2016 VL 193 MA A4296 PG 2 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA EG0VE UT WOS:000390749603679 ER PT J AU Cloonan, SM Glass, K Laucho-Contreras, M Bhashyam, AR Cervo, M Pabon, M Konrad, C Polverino, F Siempos, II Perez, E Mizumura, K Ghosh, M Parameswaran, H Williams, N Rooney, KT Chen, ZH Goldklang, MP Yuan, GC Moore, S DeMeo, DL Rouault, TA D'Armiento, JM Schon, E Manfredi, G Quackenbush, J Mahmood, A Silverman, EK Owen, CA Choi, AMK AF Cloonan, S. M. Glass, K. Laucho-Contreras, M. Bhashyam, A. R. Cervo, M. Pabon, M. Konrad, C. Polverino, F. Siempos, I. I. Perez, E. Mizumura, K. Ghosh, M. Parameswaran, H. Williams, N. Rooney, K. T. Chen, Z-H. Goldklang, M. P. Yuan, G-C. Moore, S. DeMeo, D. L. Rouault, T. A. D'Armiento, J. M. Schon, E. Manfredi, G. Quackenbush, J. Mahmood, A. Silverman, E. K. Owen, C. A. Choi, A. M. K. TI Linking The COPD Susceptibility Gene Iron-Responsive Element Binding Protein 2 (irp2) With Pathological Outcomes In Experimental COPD SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Meeting Abstract CT International Conference of the American-Thoracic-Society (ATS) CY MAY 13-18, 2016 CL San Francisco, CA SP Amer Thorac Soc C1 [Cloonan, S. M.; Pabon, M.; Konrad, C.; Siempos, I. I.; Perez, E.; Mizumura, K.; Williams, N.; Rooney, K. T.; Manfredi, G.; Choi, A. M. K.] Weill Cornell Med Coll, New York, NY USA. [Glass, K.; Laucho-Contreras, M.; Bhashyam, A. R.; Chen, Z-H.; Silverman, E. K.] Brigham & Womens Hosp, 75 Francis St, Boston, MA 02115 USA. [Laucho-Contreras, M.; Bhashyam, A. R.; Chen, Z-H.] Harvard Med Sch, Boston, MA USA. [Cervo, M.; Polverino, F.; Moore, S.; Mahmood, A.; Owen, C. A.] Harvard Med Sch, Brigham & Womens Hosp, Boston, MA USA. [Ghosh, M.; Rouault, T. A.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Bethesda, MD USA. [Parameswaran, H.] Boston Univ, Boston, MA 02215 USA. [Goldklang, M. P.] Columbia Univ, New York, NY USA. [Yuan, G-C.] Dana Farber Canc Inst, Dept Biostat & Computat Biol, Boston, MA 02115 USA. [DeMeo, D. L.] Brigham & Womens Hosp, Channing Lab, Boston, MA 02115 USA. [D'Armiento, J. M.] Columbia Univ, Dept Anesthesiol, New York, NY USA. [D'Armiento, J. M.] Columbia Univ, Dept Physiol & Cellular Biophys, New York, NY USA. [D'Armiento, J. M.] Columbia Univ, Dept Med, New York, NY USA. [Schon, E.] Columbia Univ, Med Ctr, Dept Neurol, New York, NY USA. [Schon, E.] Columbia Univ, Med Ctr, Dept Genet & Dev, New York, NY USA. [Quackenbush, J.] Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU AMER THORACIC SOC PI NEW YORK PA 25 BROADWAY, 18 FL, NEW YORK, NY 10004 USA SN 1073-449X EI 1535-4970 J9 AM J RESP CRIT CARE JI Am. J. Respir. Crit. Care Med. PY 2016 VL 193 MA A4083 PG 2 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA EG0VE UT WOS:000390749603466 ER PT J AU Conlon, TM Merthan, L Gailus-Durner, V Fuchs, H De Angelis, MH Furusawa, T Bustin, M Eickelberg, O Yildirim, A AF Conlon, T. M. Merthan, L. Gailus-Durner, V. Fuchs, H. De Angelis, M. Hrabe Furusawa, T. Bustin, M. Eickelberg, O. Yildirim, A. TI Reduced Expression Of The Epigenetic Regulator Hmgn5 Enhances Susceptibility To Emphysema SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Meeting Abstract CT International Conference of the American-Thoracic-Society (ATS) CY MAY 13-18, 2016 CL San Francisco, CA SP Amer Thorac Soc C1 [Conlon, T. M.; Merthan, L.; Eickelberg, O.; Yildirim, A.] Helmholtz Zentrum Munchen, CPC, ILBD, Munich, Germany. [Gailus-Durner, V.; Fuchs, H.; De Angelis, M. Hrabe] Helmholtz Zentrum Munchen, Inst Expt Genet, German Mouse Clin, Munich, Germany. [Furusawa, T.; Bustin, M.] NCI, Prot Sect, Lab Metab, Ctr Canc Res,NIH, Bathesda, MD USA. RI Gailus-Durner, Valerie/M-7337-2014 NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER THORACIC SOC PI NEW YORK PA 25 BROADWAY, 18 FL, NEW YORK, NY 10004 USA SN 1073-449X EI 1535-4970 J9 AM J RESP CRIT CARE JI Am. J. Respir. Crit. Care Med. PY 2016 VL 193 MA A4087 PG 1 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA EG0VE UT WOS:000390749603470 ER PT J AU Fennelly, KP Brantly, M AF Fennelly, K. P. Brantly, M. TI Resolution Of Sequential Mycobacterial Infections Associated With Alpha-1-Antiprotease Therapy SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Meeting Abstract CT International Conference of the American-Thoracic-Society (ATS) CY MAY 13-18, 2016 CL San Francisco, CA SP Amer Thorac Soc C1 [Fennelly, K. P.] NHLBI, NIH, Rockville, MD USA. [Brantly, M.] Univ Florida, Gainesville, FL USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER THORACIC SOC PI NEW YORK PA 25 BROADWAY, 18 FL, NEW YORK, NY 10004 USA SN 1073-449X EI 1535-4970 J9 AM J RESP CRIT CARE JI Am. J. Respir. Crit. Care Med. PY 2016 VL 193 MA A3742 PG 1 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA EG0VE UT WOS:000390749603126 ER PT J AU Ferrada, M Sufredini, D Mazer, AJ Katz, J AF Ferrada, M. Sufredini, D. Mazer, A. J. Katz, J. TI A Rheumatologic Disorder Mimicking Asthma SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Meeting Abstract CT International Conference of the American-Thoracic-Society (ATS) CY MAY 13-18, 2016 CL San Francisco, CA SP Amer Thorac Soc C1 [Ferrada, M.; Sufredini, D.; Mazer, A. J.; Katz, J.] NIH, Bldg 10, Bethesda, MD 20892 USA. EM marcela.ferrada@nih.gov NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER THORACIC SOC PI NEW YORK PA 25 BROADWAY, 18 FL, NEW YORK, NY 10004 USA SN 1073-449X EI 1535-4970 J9 AM J RESP CRIT CARE JI Am. J. Respir. Crit. Care Med. PY 2016 VL 193 MA A3586 PG 1 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA EG0VE UT WOS:000390749602833 ER PT J AU Foster, MW Thompson, JW Brass, DM Moseley, MA Morgan, DL Palmer, SM AF Foster, M. W. Thompson, J. W. Brass, D. M. Moseley, M. A. Morgan, D. L. Palmer, S. M. TI Plasma Metabolomics Analysis Identifies Candidate Biomarkers Of Flavoring-Induced Bronchiolitis Obliterans SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Meeting Abstract CT International Conference of the American-Thoracic-Society (ATS) CY MAY 13-18, 2016 CL San Francisco, CA SP Amer Thorac Soc C1 [Foster, M. W.; Thompson, J. W.; Brass, D. M.; Moseley, M. A.; Palmer, S. M.] Duke Univ, Med Ctr, Durham, NC USA. [Morgan, D. L.] NIEHS, Durham, NC USA. EM mwfoster@duke.edu NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER THORACIC SOC PI NEW YORK PA 25 BROADWAY, 18 FL, NEW YORK, NY 10004 USA SN 1073-449X EI 1535-4970 J9 AM J RESP CRIT CARE JI Am. J. Respir. Crit. Care Med. PY 2016 VL 193 MA A6452 PG 1 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA EG0VE UT WOS:000390749606223 ER PT J AU Foster, MW Gwinn, WM Kelly, FL Brass, DM Thompson, JW Moseley, MA Morgan, DL Palmer, SM AF Foster, M. W. Gwinn, W. M. Kelly, F. L. Brass, D. M. Thompson, J. W. Moseley, M. A. Morgan, D. L. Palmer, S. M. TI Proteomic Analysis Reveals Significant Epithelial Remodeling After In Vitro Exposure To Diacetyl Vapor SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Meeting Abstract CT International Conference of the American-Thoracic-Society (ATS) CY MAY 13-18, 2016 CL San Francisco, CA SP Amer Thorac Soc C1 [Foster, M. W.; Kelly, F. L.; Brass, D. M.; Thompson, J. W.; Moseley, M. A.; Palmer, S. M.] Duke Univ, Med Ctr, Durham, NC USA. [Gwinn, W. M.; Morgan, D. L.] NIEHS, Durham, NC USA. EM mwfoster@duke.edu NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER THORACIC SOC PI NEW YORK PA 25 BROADWAY, 18 FL, NEW YORK, NY 10004 USA SN 1073-449X EI 1535-4970 J9 AM J RESP CRIT CARE JI Am. J. Respir. Crit. Care Med. PY 2016 VL 193 MA A4080 PG 1 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA EG0VE UT WOS:000390749603463 ER PT J AU Galiatsatos, P Dababneh, D Friedlander, T Feller-Kopman, DJ Kelly, D Finucane, T Bellantoni, M Pearse, DB Greenough, W AF Galiatsatos, P. Dababneh, D. Friedlander, T. Feller-Kopman, D. J. Kelly, D. Finucane, T. Bellantoni, M. Pearse, D. B. Greenough, W. TI Long Term Outcomes From A Single Chronic Ventilator Unit: A 5-Year Assessment SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Meeting Abstract CT International Conference of the American-Thoracic-Society (ATS) CY MAY 13-18, 2016 CL San Francisco, CA SP Amer Thorac Soc C1 [Galiatsatos, P.] NIH, Bldg 10, Bethesda, MD 20892 USA. [Dababneh, D.; Friedlander, T.; Kelly, D.; Finucane, T.; Bellantoni, M.; Pearse, D. B.; Greenough, W.] Johns Hopkins Med, Baltimore, MD USA. [Feller-Kopman, D. J.] Johns Hopkins Univ, Baltimore, MD USA. EM panagis.galiatsatos@nih.gov NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER THORACIC SOC PI NEW YORK PA 25 BROADWAY, 18 FL, NEW YORK, NY 10004 USA SN 1073-449X EI 1535-4970 J9 AM J RESP CRIT CARE JI Am. J. Respir. Crit. Care Med. PY 2016 VL 193 MA A3654 PG 1 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA EG0VE UT WOS:000390749603038 ER PT J AU Gesthalter, YB Lenburg, M Limburg, PJ Mandrekar, SJ Lam, S Fursa, K Kaufman, SF Seisler, D Szabo, E Spira, A Beane, J AF Gesthalter, Y. B. Lenburg, M. Limburg, P. J. Mandrekar, S. J. Lam, S. Fursa, K. Kaufman, S. F. Seisler, D. Szabo, E. Spira, A. Beane, J. TI Chemoprevention With Myo-INOSitol Alters Gene-Expression In The Airway Epithelium Of Smokers With Dysplasia SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Meeting Abstract CT International Conference of the American-Thoracic-Society (ATS) CY MAY 13-18, 2016 CL San Francisco, CA SP Amer Thorac Soc C1 [Gesthalter, Y. B.; Lenburg, M.; Spira, A.; Beane, J.] Boston Univ, Sch Med, Boston, MA 02118 USA. [Limburg, P. J.; Mandrekar, S. J.; Fursa, K.; Kaufman, S. F.; Seisler, D.] Mayo Clin, Rochester, MN USA. [Lam, S.] Univ British Columbia, Vancouver, BC, Canada. [Szabo, E.] NCI, Bethesda, MD 20892 USA. EM ygesty@gmail.com NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER THORACIC SOC PI NEW YORK PA 25 BROADWAY, 18 FL, NEW YORK, NY 10004 USA SN 1073-449X EI 1535-4970 J9 AM J RESP CRIT CARE JI Am. J. Respir. Crit. Care Med. PY 2016 VL 193 MA A7536 PG 1 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA EG0VE UT WOS:000390749607471 ER PT J AU Glasgow, CG Pacheco-Rodriguez, G Steagall, WK Julien-Williams, P Stylianou, M Moss, J AF Glasgow, C. G. Pacheco-Rodriguez, G. Steagall, W. K. Julien-Williams, P. Stylianou, M. Moss, J. TI Ca-125 In Lymphangioleiomyomatosis Correlates With Disease Progression And Sirolimus Therapy SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Meeting Abstract CT International Conference of the American-Thoracic-Society (ATS) CY MAY 13-18, 2016 CL San Francisco, CA SP Amer Thorac Soc C1 [Glasgow, C. G.; Pacheco-Rodriguez, G.; Steagall, W. K.; Julien-Williams, P.; Stylianou, M.; Moss, J.] NIH, Bldg 10, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER THORACIC SOC PI NEW YORK PA 25 BROADWAY, 18 FL, NEW YORK, NY 10004 USA SN 1073-449X EI 1535-4970 J9 AM J RESP CRIT CARE JI Am. J. Respir. Crit. Care Med. PY 2016 VL 193 MA A6278 PG 1 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA EG0VE UT WOS:000390749606050 ER PT J AU Gowdy, KM McPeek, M Yaeger, MJ Luo, B Malur, A Thomassen, M Fessler, MB AF Gowdy, K. M. McPeek, M. Yaeger, M. J. Luo, B. Malur, A. Thomassen, M. Fessler, M. B. TI Scavenger Receptor B-I Protects The Lung From Influenza Induced Inflammation SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Meeting Abstract CT International Conference of the American-Thoracic-Society (ATS) CY MAY 13-18, 2016 CL San Francisco, CA SP Amer Thorac Soc C1 [Gowdy, K. M.; McPeek, M.; Yaeger, M. J.; Luo, B.; Malur, A.; Thomassen, M.] East Carolina Univ, Greenville, NC USA. [Fessler, M. B.] NIEHS, NIH, POB 12233, Res Triangle Pk, NC 27709 USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU AMER THORACIC SOC PI NEW YORK PA 25 BROADWAY, 18 FL, NEW YORK, NY 10004 USA SN 1073-449X EI 1535-4970 J9 AM J RESP CRIT CARE JI Am. J. Respir. Crit. Care Med. PY 2016 VL 193 MA A6724 PG 1 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA EG0VE UT WOS:000390749606495 ER PT J AU Gudmundsson, G Putman, RK Araki, T Gudmundsson, EF Nishino, M Sigurdsson, S Eiriksdottir, G Aspelund, T Launer, LJ Harris, TB Rosas, IO Schwartz, DA Hatabu, H Gudnason, V Hunninghake, GM AF Gudmundsson, G. Putman, R. K. Araki, T. Gudmundsson, E. F. Nishino, M. Sigurdsson, S. Eiriksdottir, G. Aspelund, T. Launer, L. J. Harris, T. B. Rosas, I. O. Schwartz, D. A. Hatabu, H. Gudnason, V. Hunninghake, G. M. TI Muc5b And Radiologic Subtypes Of Interstitial Lung Abnormalities In The Ages-Reykjavik Study SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Meeting Abstract CT International Conference of the American-Thoracic-Society (ATS) CY MAY 13-18, 2016 CL San Francisco, CA SP Amer Thorac Soc C1 [Gudmundsson, G.] Landspital Univ Hosp, Reykjavik, Iceland. [Putman, R. K.; Araki, T.; Nishino, M.; Rosas, I. O.; Hatabu, H.; Hunninghake, G. M.] Brigham & Womens Hosp, 75 Francis St, Boston, MA 02115 USA. [Gudmundsson, E. F.; Sigurdsson, S.; Eiriksdottir, G.; Aspelund, T.; Gudnason, V.] Iceland Heart Assoc, Kopavogur, Iceland. [Launer, L. J.] NIA, Bethesda, MD 20892 USA. [Harris, T. B.] NIA, NIH, Baltimore, MD 21224 USA. [Schwartz, D. A.] Univ Colorado, Aurora, CO USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER THORACIC SOC PI NEW YORK PA 25 BROADWAY, 18 FL, NEW YORK, NY 10004 USA SN 1073-449X EI 1535-4970 J9 AM J RESP CRIT CARE JI Am. J. Respir. Crit. Care Med. PY 2016 VL 193 MA A6219 PG 1 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA EG0VE UT WOS:000390749605879 ER PT J AU Gulleman, PM White, CS Han, W Plosa, EJ Gochuico, B Gahl, W Blackwell, TS Young, LR AF Gulleman, P. M. White, C. S. Han, W. Plosa, E. J. Gochuico, B. Gahl, W. Blackwell, T. S. Young, L. R. TI Epithelial Nox4 Contributes To Fibrotic Susceptibility In Hermansky-Pudlak Syndrome Mice SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Meeting Abstract CT International Conference of the American-Thoracic-Society (ATS) CY MAY 13-18, 2016 CL San Francisco, CA SP Amer Thorac Soc C1 [Gulleman, P. M.; White, C. S.; Han, W.; Plosa, E. J.; Blackwell, T. S.; Young, L. R.] Vanderbilt Univ, 221 Kirkland Hall, Nashville, TN 37235 USA. [Gochuico, B.; Gahl, W.] NHGRI, NIH, Bethesda, MD 20892 USA. EM lisa.young@vanderbilt.edu NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER THORACIC SOC PI NEW YORK PA 25 BROADWAY, 18 FL, NEW YORK, NY 10004 USA SN 1073-449X EI 1535-4970 J9 AM J RESP CRIT CARE JI Am. J. Respir. Crit. Care Med. PY 2016 VL 193 MA A2393 PG 1 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA EG0VE UT WOS:000390749601533 ER PT J AU Hasday, JD Scheraga, RG Thompson, C Tulapurkar, M Cowan, MJ Sun, J Cai, R Logun, C Todd, NW Shelhamer, J Atamas, SP Luzina, IG AF Hasday, J. D. Scheraga, R. G. Thompson, C. Tulapurkar, M. Cowan, M. J. Sun, J. Cai, R. Logun, C. Todd, N. W. Shelhamer, J. Atamas, S. P. Luzina, I. G. TI Heat-Shock Accelerates Human Lung Epithelial Wound Healing By Activating Expression Of Fibroblast Growth Factor (fgf)-1: Implications For Idiopathic Pulmonary Fibrosis (ipf) SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Meeting Abstract CT International Conference of the American-Thoracic-Society (ATS) CY MAY 13-18, 2016 CL San Francisco, CA SP Amer Thorac Soc C1 [Hasday, J. D.; Tulapurkar, M.; Todd, N. W.] Univ Maryland, Med Ctr, Baltimore, MD 21201 USA. [Scheraga, R. G.] Cleveland Clin, Cleveland, OH 44106 USA. [Thompson, C.] Loyola Univ Maryland, Baltimore, MD USA. [Cowan, M. J.; Atamas, S. P.; Luzina, I. G.] Univ Maryland, Baltimore, MD 21201 USA. [Sun, J.; Cai, R.; Logun, C.; Shelhamer, J.] NIH, Bldg 10, Bethesda, MD 20892 USA. EM Jhasday@medicine.umaryland.edu NR 0 TC 0 Z9 0 U1 1 U2 1 PU AMER THORACIC SOC PI NEW YORK PA 25 BROADWAY, 18 FL, NEW YORK, NY 10004 USA SN 1073-449X EI 1535-4970 J9 AM J RESP CRIT CARE JI Am. J. Respir. Crit. Care Med. PY 2016 VL 193 MA A1461 PG 1 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA EG0VE UT WOS:000390749600460 ER PT J AU Hooper, LG Young, MT Keller, JP Szpiro, A O'Brien, KM Sandler, DP Vedal, S Kaufman, J London, S AF Hooper, L. G. Young, M. T. Keller, J. P. Szpiro, A. O'Brien, K. M. Sandler, D. P. Vedal, S. Kaufman, J. London, S. TI Ambient Air Pollution Exposure And Chronic Bronchitis In A Cohort Of U. S. Women SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Meeting Abstract CT International Conference of the American-Thoracic-Society (ATS) CY MAY 13-18, 2016 CL San Francisco, CA SP Amer Thorac Soc C1 [Hooper, L. G.; Young, M. T.; Keller, J. P.; Szpiro, A.; Vedal, S.; Kaufman, J.] Univ Washington, Seattle, WA 98195 USA. [O'Brien, K. M.; Sandler, D. P.; London, S.] Natl Inst Environm Hlth Sci, Res Triangle Pk, NC USA. EM lghooper@uw.edu NR 0 TC 0 Z9 0 U1 1 U2 1 PU AMER THORACIC SOC PI NEW YORK PA 25 BROADWAY, 18 FL, NEW YORK, NY 10004 USA SN 1073-449X EI 1535-4970 J9 AM J RESP CRIT CARE JI Am. J. Respir. Crit. Care Med. PY 2016 VL 193 MA A2991 PG 1 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA EG0VE UT WOS:000390749602239 ER PT J AU House, JS Wyss, AB Hoppin, JA Umbach, DM London, S AF House, J. S. Wyss, A. B. Hoppin, J. A. Umbach, D. M. London, S. CA Agr Lung Hlth Study TI Early-Life Farming Exposures And Adult Atopy: The Agricultural Lung Health Study SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Meeting Abstract CT International Conference of the American-Thoracic-Society (ATS) CY MAY 13-18, 2016 CL San Francisco, CA SP Amer Thorac Soc C1 [House, J. S.; Wyss, A. B.; Umbach, D. M.; London, S.] NIEHS, Res Triangle Pk, NC USA. [Hoppin, J. A.] North Carolina State Univ, Raleigh, NC USA. EM john.house@nih.gov NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER THORACIC SOC PI NEW YORK PA 25 BROADWAY, 18 FL, NEW YORK, NY 10004 USA SN 1073-449X EI 1535-4970 J9 AM J RESP CRIT CARE JI Am. J. Respir. Crit. Care Med. PY 2016 VL 193 MA A6695 PG 1 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA EG0VE UT WOS:000390749606466 ER PT J AU Johnson, CG Sciurba, J Rice, A Aloor, J Cyphert, J Bulek, K Li, X Fessler, MB Garantziotis, S AF Johnson, C. G. Sciurba, J. Rice, A. Aloor, J. Cyphert, J. Bulek, K. Li, X. Fessler, M. B. Garantziotis, S. TI Toll-Like Receptor 5 Modulates Myd88-Dependent Toll-Like Receptor 4 Signaling SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Meeting Abstract CT International Conference of the American-Thoracic-Society (ATS) CY MAY 13-18, 2016 CL San Francisco, CA SP Amer Thorac Soc C1 [Johnson, C. G.; Sciurba, J.; Rice, A.; Aloor, J.; Cyphert, J.; Fessler, M. B.; Garantziotis, S.] NIEHS, NIH, POB 12233, Res Triangle Pk, NC 27709 USA. [Bulek, K.; Li, X.] Cleveland Clin, Lerner Res Inst, Cleveland, OH 44106 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER THORACIC SOC PI NEW YORK PA 25 BROADWAY, 18 FL, NEW YORK, NY 10004 USA SN 1073-449X EI 1535-4970 J9 AM J RESP CRIT CARE JI Am. J. Respir. Crit. Care Med. PY 2016 VL 193 MA A2643 PG 1 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA EG0VE UT WOS:000390749601783 ER PT J AU Kadri, SS Spaulding, AB Lai, Y Adjemian, J Prevots, DR Palmore, T Masur, H Rhee, C Klompas, M Dekker, J Suffredini, A Hooper, DC Fridkin, S Danner, RL AF Kadri, S. S. Spaulding, A. B. Lai, Y. Adjemian, J. Prevots, D. R. Palmore, T. Masur, H. Rhee, C. Klompas, M. Dekker, J. Suffredini, A. Hooper, D. C. Fridkin, S. Danner, R. L. CA NIH Antimicrobial Resistance TI Five-Year Trends In Difficult To Treat Antimicrobial-Resistant Gram-Negative Bloodstream Infections Among Inpatients At 180 Us Hospitals SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Meeting Abstract CT International Conference of the American-Thoracic-Society (ATS) CY MAY 13-18, 2016 CL San Francisco, CA SP Amer Thorac Soc C1 [Kadri, S. S.; Palmore, T.; Masur, H.; Dekker, J.; Suffredini, A.; Danner, R. L.] NIH, Ctr Clin, Bethesda, MD 20892 USA. [Spaulding, A. B.; Lai, Y.; Adjemian, J.; Prevots, D. R.] NIAID, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA. [Rhee, C.; Klompas, M.] Harvard Med Sch, Harvard Pilgrim Hlth Care Inst, Boston, MA USA. [Hooper, D. C.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Fridkin, S.] US Ctr Dis Control & Prevent, Atlanta, GA USA. EM sameer.kadri@nih.gov NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER THORACIC SOC PI NEW YORK PA 25 BROADWAY, 18 FL, NEW YORK, NY 10004 USA SN 1073-449X EI 1535-4970 J9 AM J RESP CRIT CARE JI Am. J. Respir. Crit. Care Med. PY 2016 VL 193 MA A6911 PG 2 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA EG0VE UT WOS:000390749606682 ER PT J AU Kanth, SM Baker, ES Van Dyke, AL Donahoe, M AF Kanth, S. M. Baker, E. S. Van Dyke, A. L. Donahoe, M. TI A Rare Case Of Pleural Effusion In A 92-Year-Old Man SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Meeting Abstract CT International Conference of the American-Thoracic-Society (ATS) CY MAY 13-18, 2016 CL San Francisco, CA SP Amer Thorac Soc C1 [Kanth, S. M.] Univ Pittsburgh, Med Ctr, Pittsburgh, PA USA. [Van Dyke, A. L.] NCI, Bethesda, MD 20892 USA. EM kanthsm@upmc.edu NR 3 TC 0 Z9 0 U1 0 U2 0 PU AMER THORACIC SOC PI NEW YORK PA 25 BROADWAY, 18 FL, NEW YORK, NY 10004 USA SN 1073-449X EI 1535-4970 J9 AM J RESP CRIT CARE JI Am. J. Respir. Crit. Care Med. PY 2016 VL 193 MA A3322 PG 2 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA EG0VE UT WOS:000390749602570 ER PT J AU KleinJan, A Koekoek, E Lukkes, M De Bruijn, M Van Nimwegen, M Beute, J Manganiello, V Hendriks, R AF KleinJan, A. Koekoek, E. Lukkes, M. De Bruijn, M. Van Nimwegen, M. Beute, J. Manganiello, V. Hendriks, R. TI Phosphodiesterase Iii Plays A Crucial Role In The Pathophysiology Of Asthma SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Meeting Abstract CT International Conference of the American-Thoracic-Society (ATS) CY MAY 13-18, 2016 CL San Francisco, CA SP Amer Thorac Soc C1 [KleinJan, A.; Koekoek, E.; Lukkes, M.; De Bruijn, M.; Van Nimwegen, M.; Beute, J.; Hendriks, R.] Erasmus MC, Rotterdam, Netherlands. [Manganiello, V.] NIH, Bldg 10, Bethesda, MD 20892 USA. EM a.kleinjan@erasmusmc.nl NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER THORACIC SOC PI NEW YORK PA 25 BROADWAY, 18 FL, NEW YORK, NY 10004 USA SN 1073-449X EI 1535-4970 J9 AM J RESP CRIT CARE JI Am. J. Respir. Crit. Care Med. PY 2016 VL 193 MA A6704 PG 1 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA EG0VE UT WOS:000390749606475 ER PT J AU London, S Hoppin, JA Wyss, A House, JS Henneberger, PK Umbach, DM Thorne, PS Carnes, MU AF London, S. Hoppin, J. A. Wyss, A. House, J. S. Henneberger, P. K. Umbach, D. M. Thorne, P. S. Carnes, M. U. TI House Dust Endotoxin Levels Are Associated With Adult Asthma In The Agricultural Lung Health Study SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Meeting Abstract CT International Conference of the American-Thoracic-Society (ATS) CY MAY 13-18, 2016 CL San Francisco, CA SP Amer Thorac Soc C1 [London, S.; Wyss, A.; House, J. S.; Umbach, D. M.; Carnes, M. U.] NIEHS, POB 12233, Res Triangle Pk, NC 27709 USA. [Hoppin, J. A.] North Carolina State Univ, Raleigh, NC USA. [Henneberger, P. K.] CDC Natl Inst Occupat Safety & Hlth NIOSH, Morgantown, WV USA. [Thorne, P. S.] Univ Iowa, Iowa City, IA USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU AMER THORACIC SOC PI NEW YORK PA 25 BROADWAY, 18 FL, NEW YORK, NY 10004 USA SN 1073-449X EI 1535-4970 J9 AM J RESP CRIT CARE JI Am. J. Respir. Crit. Care Med. PY 2016 VL 193 MA A2781 PG 1 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA EG0VE UT WOS:000390749602030 ER PT J AU Mazer, AJ Cai, R Sun, J Graninger, G Harper, B Ferreyra, G Danner, RL Solomon, MA Elinoff, JM AF Mazer, A. J. Cai, R. Sun, J. Graninger, G. Harper, B. Ferreyra, G. Danner, R. L. Solomon, M. A. Elinoff, J. M. TI Meta-Analysis Of Peripheral Blood Mononuclear Cell Genome-Wide Expression Profiling In Pulmonary Arterial Hypertension SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Meeting Abstract CT International Conference of the American-Thoracic-Society (ATS) CY MAY 13-18, 2016 CL San Francisco, CA SP Amer Thorac Soc C1 [Mazer, A. J.; Cai, R.; Sun, J.; Graninger, G.; Harper, B.; Ferreyra, G.; Danner, R. L.; Elinoff, J. M.] NIH, Crit Care Med Dept, Ctr Clin, Bldg 10, Bethesda, MD 20892 USA. [Solomon, M. A.] NHLBI, Crit Care Med Dept, NIH, Bldg 10, Bethesda, MD 20892 USA. [Solomon, M. A.] NHLBI, Cardiovasc & Pulm Branch, NIH, Bldg 10, Bethesda, MD 20892 USA. EM adrien.mazer@nih.gov NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER THORACIC SOC PI NEW YORK PA 25 BROADWAY, 18 FL, NEW YORK, NY 10004 USA SN 1073-449X EI 1535-4970 J9 AM J RESP CRIT CARE JI Am. J. Respir. Crit. Care Med. PY 2016 VL 193 MA A4619 PG 2 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA EG0VE UT WOS:000390749604135 ER PT J AU Nardell, EA Williams, CM Bell, AJ Malinga, L Ramsheh, MY Bakir, A Garton, NJ Stoltz, A DeKock, E Waddell, S Hinton, J Fennelly, K Barer, M AF Nardell, E. A. Williams, C. M. Bell, A. J. Malinga, L. Ramsheh, M. Y. Bakir, A. Garton, N. J. Stoltz, A. DeKock, E. Waddell, S. Hinton, J. Fennelly, K. Barer, M. TI Tb Airborne Transmission: First Gene Expression Signatures Of Captured, Uncultured M. Tuberculosis From Human Source Aerosol SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Meeting Abstract CT International Conference of the American-Thoracic-Society (ATS) CY MAY 13-18, 2016 CL San Francisco, CA SP Amer Thorac Soc C1 [Nardell, E. A.] Brigham & Womens Hosp, 75 Francis St, Boston, MA 02115 USA. [Williams, C. M.; Bell, A. J.; Ramsheh, M. Y.; Bakir, A.; Garton, N. J.; Barer, M.] Univ Leicester, Leicester, Leics, England. [Malinga, L.; Stoltz, A.; DeKock, E.] Univ Pretoria, Pretoria, South Africa. [Waddell, S.] Univ Sussex, Brighton, E Sussex, England. [Hinton, J.] Univ Liverpool, Liverpool, Merseyside, England. [Fennelly, K.] NHLBI, Bldg 10, Bethesda, MD 20892 USA. EM enardell@gmail.com NR 0 TC 0 Z9 0 U1 2 U2 2 PU AMER THORACIC SOC PI NEW YORK PA 25 BROADWAY, 18 FL, NEW YORK, NY 10004 USA SN 1073-449X EI 1535-4970 J9 AM J RESP CRIT CARE JI Am. J. Respir. Crit. Care Med. PY 2016 VL 193 MA A7934 PG 1 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA EG0VE UT WOS:000390749608023 ER PT J AU Narute, P Cai, R Sun, J Suffredini, A AF Narute, P. Cai, R. Sun, J. Suffredini, A. TI Microrna Found In Human Airway Secretions Modulate The Nfkb Pathway SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Meeting Abstract CT International Conference of the American-Thoracic-Society (ATS) CY MAY 13-18, 2016 CL San Francisco, CA SP Amer Thorac Soc C1 [Narute, P.; Cai, R.; Sun, J.] NIH, Bldg 10, Bethesda, MD 20892 USA. [Suffredini, A.] NIH, Ctr Clin, Bethesda, MD 20892 USA. EM asuffredini@cc.nih.gov NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER THORACIC SOC PI NEW YORK PA 25 BROADWAY, 18 FL, NEW YORK, NY 10004 USA SN 1073-449X EI 1535-4970 J9 AM J RESP CRIT CARE JI Am. J. Respir. Crit. Care Med. PY 2016 VL 193 MA A6279 PG 1 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA EG0VE UT WOS:000390749606051 ER PT J AU Nguyen, JA Prevots, DR Adjemian, J Strollo, SE Daniels, M Daley, CL Knowles, M Olivier, KN AF Nguyen, J. A. Prevots, D. R. Adjemian, J. Strollo, S. E. Daniels, M. Daley, C. L. Knowles, M. Olivier, K. N. TI Characterization Of Idiopathic Bronchiectasis In Patients With And Without Pulmonary Nontuberculous Mycobacterial Disease SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Meeting Abstract CT International Conference of the American-Thoracic-Society (ATS) CY MAY 13-18, 2016 CL San Francisco, CA SP Amer Thorac Soc C1 [Nguyen, J. A.; Olivier, K. N.] NHLBI, Bldg 10, Bethesda, MD 20892 USA. [Prevots, D. R.; Adjemian, J.; Strollo, S. E.] NIAID, NIH, Bethesda, MD 20892 USA. [Daniels, M.; Knowles, M.] Univ North Carolina Chapel Hill, Chapel Hill, NC USA. [Daley, C. L.] Natl Jewish Hlth, Denver, CO USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER THORACIC SOC PI NEW YORK PA 25 BROADWAY, 18 FL, NEW YORK, NY 10004 USA SN 1073-449X EI 1535-4970 J9 AM J RESP CRIT CARE JI Am. J. Respir. Crit. Care Med. PY 2016 VL 193 MA A1758 PG 1 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA EG0VE UT WOS:000390749600757 ER PT J AU Olivier, KN Maas-Moreno, R Whatley, M Cheng, K Lee, JH Fiorentino, C Shaffer, R Macdonald, S Gupta, R Corcoran, TE Malinin, VS Eagle, G Perkins, W Paik, C Chen, C AF Olivier, K. N. Maas-Moreno, R. Whatley, M. Cheng, K. Lee, J. -H. Fiorentino, C. Shaffer, R. Macdonald, S. Gupta, R. Corcoran, T. E. Malinin, V. S. Eagle, G. Perkins, W. Paik, C. Chen, C. TI Airway Deposition And Retention Of Liposomal Amikacin For Inhalation In Patients With Pulmonary Nontuberculous Mycobacterial Disease SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Meeting Abstract CT International Conference of the American-Thoracic-Society (ATS) CY MAY 13-18, 2016 CL San Francisco, CA SP Amer Thorac Soc C1 [Olivier, K. N.; Maas-Moreno, R.; Whatley, M.; Cheng, K.; Lee, J. -H.; Macdonald, S.; Paik, C.; Chen, C.] NHLBI, Bldg 10, Bethesda, MD 20892 USA. [Fiorentino, C.; Shaffer, R.] NIAID, 9000 Rockville Pike, Bethesda, MD 20892 USA. [Gupta, R.] Contravir Pharmaceut, Edison, NJ USA. [Corcoran, T. E.] Univ Pittsburgh, Pittsburgh, PA USA. [Malinin, V. S.; Eagle, G.; Perkins, W.] Insmed Inc, Bridgewater, NJ USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU AMER THORACIC SOC PI NEW YORK PA 25 BROADWAY, 18 FL, NEW YORK, NY 10004 USA SN 1073-449X EI 1535-4970 J9 AM J RESP CRIT CARE JI Am. J. Respir. Crit. Care Med. PY 2016 VL 193 MA A3732 PG 1 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA EG0VE UT WOS:000390749603116 ER PT J AU Olivier, KN Griffith, DE Winthrop, KL Brown-Elliott, BA Eagle, G McGinnis, J Wallace, RJ AF Olivier, K. N. Griffith, D. E. Winthrop, K. L. Brown-Elliott, B. A. Eagle, G. McGinnis, J. Wallace, R. J. TI 12-Month Follow-Up Data From A Phase 2 Trial Of Liposomal Amikacin For Inhalation (lai) In Patients With Refractory Nontuberculous Mycobacterial (ntm) Lung Infection SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Meeting Abstract CT International Conference of the American-Thoracic-Society (ATS) CY MAY 13-18, 2016 CL San Francisco, CA SP Amer Thorac Soc C1 [Olivier, K. N.] NHLBI, Bldg 10, Bethesda, MD 20892 USA. [Griffith, D. E.; Brown-Elliott, B. A.; Wallace, R. J.] Univ Texas Hlth Sci Ctr Tyler, Tyler, TX USA. [Winthrop, K. L.] Oregon Hlth & Sci Univ, Portland, OR USA. [Eagle, G.; McGinnis, J.] Insmed Inc, Bridgewater, NJ USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU AMER THORACIC SOC PI NEW YORK PA 25 BROADWAY, 18 FL, NEW YORK, NY 10004 USA SN 1073-449X EI 1535-4970 J9 AM J RESP CRIT CARE JI Am. J. Respir. Crit. Care Med. PY 2016 VL 193 MA A3722 PG 1 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA EG0VE UT WOS:000390749603106 ER PT J AU Patel, V Sampat, V Espey, MG Sitapara, R Wang, H Yang, X Ashby, CR Thomas, DD Mantell, LL AF Patel, V. Sampat, V. Espey, M. G. Sitapara, R. Wang, H. Yang, X. Ashby, C. R. Thomas, D. D. Mantell, L. L. TI Ascorbic Acid Attenuates Hyperoxia-Compromised Host Defense Against Pulmonary Bacterial Infection SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Meeting Abstract CT International Conference of the American-Thoracic-Society (ATS) CY MAY 13-18, 2016 CL San Francisco, CA SP Amer Thorac Soc C1 [Patel, V.; Sampat, V.; Sitapara, R.; Yang, X.; Ashby, C. R.; Mantell, L. L.] St Johns Univ, Jamaica, NY 11439 USA. [Espey, M. G.] NCI, Bethesda, MD 20892 USA. [Wang, H.] North Shore LIJ Hlth Sci, Feinstein Inst Med Res, Manhasset, NY USA. [Thomas, D. D.] Univ Illinois, Chicago, IL USA. EM patelvivek85@gmail.com NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER THORACIC SOC PI NEW YORK PA 25 BROADWAY, 18 FL, NEW YORK, NY 10004 USA SN 1073-449X EI 1535-4970 J9 AM J RESP CRIT CARE JI Am. J. Respir. Crit. Care Med. PY 2016 VL 193 MA A6897 PG 1 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA EG0VE UT WOS:000390749606668 ER PT J AU Paulin-Prado, P Nishimura, K Freimanis-Hance, L Hunsberger, S Beigel, J Galindo-Fraga, A Ortiz-Hernandez, AA Llamosas-Gallardo, B Moreno-Espinosa, S Valdez-Vazquez, R Magana-Aquino, M Ruiz-Palacios, GM Ramirez-Venegas, A AF Paulin-Prado, P. Nishimura, K. Freimanis-Hance, L. Hunsberger, S. Beigel, J. Galindo-Fraga, A. Ortiz-Hernandez, A. A. Llamosas-Gallardo, B. Moreno-Espinosa, S. Valdez-Vazquez, R. Magana-Aquino, M. Ruiz-Palacios, G. M. Ramirez-Venegas, A. TI Clinical Characteristics Of Asthmatic Patients With Influenza-Like Illness And Risk For Severe Exacerbations In Mexico SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Meeting Abstract CT International Conference of the American-Thoracic-Society (ATS) CY MAY 13-18, 2016 CL San Francisco, CA SP Amer Thorac Soc C1 [Paulin-Prado, P.; Ramirez-Venegas, A.] Inst Nacl Enfermedades Resp, Mexico City, DF, Mexico. [Nishimura, K.; Hunsberger, S.] NIAID, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA. [Freimanis-Hance, L.] Westat Corp, Rockville, MD USA. [Beigel, J.] Leidos Biomed, Bethesda, MD USA. [Galindo-Fraga, A.; Ruiz-Palacios, G. M.] Inst Nacl Ciencias Med & Nutr Salvador Zubiran, Mexico City, DF, Mexico. [Ortiz-Hernandez, A. A.; Llamosas-Gallardo, B.] Inst Nacl Pediat, Mexico City, DF, Mexico. [Moreno-Espinosa, S.] Hosp Infantil Mexico Dr Federico Gomez, Mexico City, DF, Mexico. [Valdez-Vazquez, R.] Hosp Gen & Alta Especialidad Dr Manuel Gea Gonzal, Mexico City, DF, Mexico. [Magana-Aquino, M.] Univ Autonoma San Luis Potosi, Hosp Cent Dr Ignacio Morones Prieto, San Luis Potosi, Mexico. EM paulinapaulin@yahoo.com.mx NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER THORACIC SOC PI NEW YORK PA 25 BROADWAY, 18 FL, NEW YORK, NY 10004 USA SN 1073-449X EI 1535-4970 J9 AM J RESP CRIT CARE JI Am. J. Respir. Crit. Care Med. PY 2016 VL 193 MA A4971 PG 1 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA EG0VE UT WOS:000390749604485 ER PT J AU Pepper, DJ Sun, J Welsh, J Cui, X Suffredini, A Eichacker, P AF Pepper, D. J. Sun, J. Welsh, J. Cui, X. Suffredini, A. Eichacker, P. TI The Adjusted Effect Of Increased Body Mass Index On Mortality In Patients Requiring Icu Admission For Severe Sepsis And Septic Shock Or Influenza: A Systematic Review And Meta-Analysis SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Meeting Abstract CT International Conference of the American-Thoracic-Society (ATS) CY MAY 13-18, 2016 CL San Francisco, CA SP Amer Thorac Soc C1 [Pepper, D. J.; Sun, J.; Welsh, J.; Cui, X.; Suffredini, A.; Eichacker, P.] NIH, Bldg 10, Bethesda, MD 20892 USA. EM dominiquepepper@gmail.com NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER THORACIC SOC PI NEW YORK PA 25 BROADWAY, 18 FL, NEW YORK, NY 10004 USA SN 1073-449X EI 1535-4970 J9 AM J RESP CRIT CARE JI Am. J. Respir. Crit. Care Med. PY 2016 VL 193 MA A3687 PG 2 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA EG0VE UT WOS:000390749603071 ER PT J AU Pepper, DJ Delbecq, E Ioffe, O White, C Britt, E AF Pepper, D. J. Delbecq, E. Ioffe, O. White, C. Britt, E. TI Pleural Extramedullary Hematopoiesis: A Rare Cause Of Bloody Pleural Effusion SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Meeting Abstract CT International Conference of the American-Thoracic-Society (ATS) CY MAY 13-18, 2016 CL San Francisco, CA SP Amer Thorac Soc C1 [Pepper, D. J.] NIH, Bldg 10, Bethesda, MD 20892 USA. [Delbecq, E.; Ioffe, O.; White, C.; Britt, E.] Univ Maryland Med Syst, Baltimore, MD USA. EM dominiquepepper@gmail.com NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER THORACIC SOC PI NEW YORK PA 25 BROADWAY, 18 FL, NEW YORK, NY 10004 USA SN 1073-449X EI 1535-4970 J9 AM J RESP CRIT CARE JI Am. J. Respir. Crit. Care Med. PY 2016 VL 193 MA A3315 PG 1 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA EG0VE UT WOS:000390749602563 ER PT J AU Pepper, DJ Delbecq, E Burke, AP White, C Britt, E AF Pepper, D. J. Delbecq, E. Burke, A. P. White, C. Britt, E. TI Concomitant Daptomycin And Ceftaroline-Induced Eosinophilic Pneumonia: A Case Report SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Meeting Abstract CT International Conference of the American-Thoracic-Society (ATS) CY MAY 13-18, 2016 CL San Francisco, CA SP Amer Thorac Soc C1 [Pepper, D. J.] NIH, Bldg 10, Bethesda, MD 20892 USA. [Delbecq, E.; Burke, A. P.; White, C.; Britt, E.] Univ Maryland Med Syst, Baltimore, MD USA. EM dominiquepepper@gmail.com NR 1 TC 0 Z9 0 U1 0 U2 0 PU AMER THORACIC SOC PI NEW YORK PA 25 BROADWAY, 18 FL, NEW YORK, NY 10004 USA SN 1073-449X EI 1535-4970 J9 AM J RESP CRIT CARE JI Am. J. Respir. Crit. Care Med. PY 2016 VL 193 MA A1654 PG 1 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA EG0VE UT WOS:000390749600653 ER PT J AU Podolanczuk, A Oelsner, EC Barr, RG Hoffman, EA Armstrong, HF Austin, JHM Basner, RC Bartels, MN Christie, JD Enright, PL Gochuico, B Stukovsky, KH Kaufman, J Nath, H Newell, JD Palmer, SM Rabinowitz, D Raghu, G Sell, J Sieren, JP Sonavane, SK Tracy, RP Watts, JR Williams, K Kawut, SM Lederer, DJ AF Podolanczuk, A. Oelsner, E. C. Barr, R. G. Hoffman, E. A. Armstrong, H. F. Austin, J. H. M. Basner, R. C. Bartels, M. N. Christie, J. D. Enright, P. L. Gochuico, B. Stukovsky, K. Hinckley Kaufman, J. Nath, H. Newell, J. D. Palmer, S. M. Rabinowitz, D. Raghu, G. Sell, J. Sieren, J. P. Sonavane, S. K. Tracy, R. P. Watts, J. R. Williams, K. Kawut, S. M. Lederer, D. J. TI High Attenuation Areas On Computed Tomography, Subclinical Interstitial Lung Disease, And Mortality In Community Dwelling Adults SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Meeting Abstract CT International Conference of the American-Thoracic-Society (ATS) CY MAY 13-18, 2016 CL San Francisco, CA SP Amer Thorac Soc C1 [Podolanczuk, A.; Oelsner, E. C.; Barr, R. G.; Armstrong, H. F.; Austin, J. H. M.; Basner, R. C.; Rabinowitz, D.; Sell, J.; Lederer, D. J.] Columbia Univ, Med Ctr, New York, NY USA. [Hoffman, E. A.; Newell, J. D.] Univ Iowa, Iowa City, IA USA. [Bartels, M. N.] Montefiore Med Ctr, Albert Einstein Coll Med, Bronx, NY 10467 USA. [Christie, J. D.; Kawut, S. M.] Univ Penn, Sch Med, Philadelphia, PA 19104 USA. [Enright, P. L.] Univ Arizona, Tucson, AZ USA. [Gochuico, B.] NHGRI, Bethesda, MD 20892 USA. [Stukovsky, K. Hinckley; Kaufman, J.; Raghu, G.; Williams, K.] Univ Washington, Seattle, WA 98195 USA. [Nath, H.; Sonavane, S. K.; Watts, J. R.] Univ Alabama Birmingham, Birmingham, AL USA. [Palmer, S. M.] Duke Univ, Sch Med, Durham, NC USA. [Sieren, J. P.] Vida Diagnost Inc, Coralville, IA USA. [Tracy, R. P.] Univ Vermont, Colchester, VT USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER THORACIC SOC PI NEW YORK PA 25 BROADWAY, 18 FL, NEW YORK, NY 10004 USA SN 1073-449X EI 1535-4970 J9 AM J RESP CRIT CARE JI Am. J. Respir. Crit. Care Med. PY 2016 VL 193 MA A4287 PG 2 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA EG0VE UT WOS:000390749603670 ER PT J AU Putman, RK Hatabu, H Araki, T Gudmundsson, G Gao, W Nishino, M Okajima, Y Dupuis, J Latourelle, J Cho, MH El-Chemaly, S Coxson, H Celli, BR Fernandez, IE Zazueta, OE Ross, JC Harmouche, R Estepar, RS Diaz, AA Sigurdsson, S Gudmundsson, E Eiriksdottir, G Aspelund, T Budoff, MJ Kinney, GL Hokanson, J Williams, MC Murchison, JT MacNee, W Hoffmann, U O'Donnell, CJ Launer, LJ Harris, TB Gudnason, V Silverman, EK O'Connor, GT Washko, G Rosas, IO Hunninghake, GM AF Putman, R. K. Hatabu, H. Araki, T. Gudmundsson, G. Gao, W. Nishino, M. Okajima, Y. Dupuis, J. Latourelle, J. Cho, M. H. El-Chemaly, S. Coxson, H. Celli, B. R. Fernandez, I. E. Zazueta, O. E. Ross, J. C. Harmouche, R. Estepar, R. San Jose Diaz, A. A. Sigurdsson, S. Gudmundsson, E. Eiriksdottir, G. Aspelund, T. Budoff, M. J. Kinney, G. L. Hokanson, J. Williams, M. C. Murchison, J. T. MacNee, W. Hoffmann, U. O'Donnell, C. J. Launer, L. J. Harris, T. B. Gudnason, V. Silverman, E. K. O'Connor, G. T. Washko, G. Rosas, I. O. Hunninghake, G. M. CA COPDGene ECLIPSE TI Mortality And Undiagnosed Interstitial Lung Abnormalities SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Meeting Abstract CT International Conference of the American-Thoracic-Society (ATS) CY MAY 13-18, 2016 CL San Francisco, CA SP Amer Thorac Soc C1 [Putman, R. K.; Hatabu, H.; Araki, T.; Nishino, M.; Okajima, Y.; Cho, M. H.; El-Chemaly, S.; Celli, B. R.; Fernandez, I. E.; Zazueta, O. E.; Ross, J. C.; Harmouche, R.; Estepar, R. San Jose; Diaz, A. A.; Silverman, E. K.; Washko, G.; Rosas, I. O.; Hunninghake, G. M.] Brigham & Womens Hosp, 75 Francis St, Boston, MA 02115 USA. [Gudmundsson, G.] Landspital Univ Hosp, Reykjavik, Iceland. [Gao, W.; Dupuis, J.; Latourelle, J.] Boston Univ, Sch Publ Hlth, Boston, MA USA. [Coxson, H.] Univ British Columbia, Vancouver, BC, Canada. [Sigurdsson, S.; Gudmundsson, E.; Eiriksdottir, G.; Aspelund, T.; Gudnason, V.] Iceland Heart Assoc, Kopavogur, Iceland. [Budoff, M. J.] Harbor UCLA, Los Angeles Biomed Res Inst, Torrance, CA USA. [Kinney, G. L.; Hokanson, J.] Univ Colorado, Colorado Sch Publ Hlth, Aurora, CO USA. [Williams, M. C.] Univ Edinburgh, British Heart Fdn, Edinburgh, Midlothian, Scotland. [Murchison, J. T.] Royal Infirm Edinburgh NHS Trust, Edinburgh, Midlothian, Scotland. [MacNee, W.] Univ Edinburgh, Edinburgh, Midlothian, Scotland. [Hoffmann, U.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [O'Donnell, C. J.] NHLBI, Bldg 10, Bethesda, MD 20892 USA. [Launer, L. J.; Harris, T. B.] NIA, NIH, Baltimore, MD 21224 USA. [O'Connor, G. T.] Boston Univ, Sch Med, Boston, MA 02118 USA. EM rputman@partners.org NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER THORACIC SOC PI NEW YORK PA 25 BROADWAY, 18 FL, NEW YORK, NY 10004 USA SN 1073-449X EI 1535-4970 J9 AM J RESP CRIT CARE JI Am. J. Respir. Crit. Care Med. PY 2016 VL 193 MA A4284 PG 2 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA EG0VE UT WOS:000390749603667 ER PT J AU Rhee, C Kadri, SS Danner, R Suffredini, A Massaro, A Kitch, BT Lee, G Kleinman, K Platt, R Klompas, M AF Rhee, C. Kadri, S. S. Danner, R. Suffredini, A. Massaro, A. Kitch, B. T. Lee, G. Kleinman, K. Platt, R. Klompas, M. TI Diagnosing Sepsis Is Subjective And Highly Variable: results From A Survey Of Intensivists Using Case Vignettes SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Meeting Abstract CT International Conference of the American-Thoracic-Society (ATS) CY MAY 13-18, 2016 CL San Francisco, CA SP Amer Thorac Soc C1 [Rhee, C.; Lee, G.; Kleinman, K.; Platt, R.; Klompas, M.] Harvard Med Sch, Harvard Pilgrim Hlth Care Inst, Boston, MA USA. [Kadri, S. S.; Danner, R.; Suffredini, A.] NIH, Ctr Clin, Bethesda, MD 20892 USA. [Massaro, A.] Brigham & Womens Hosp, 75 Francis St, Boston, MA 02115 USA. [Kitch, B. T.] North Shore Med Ctr, Salem, MA USA. EM chanu.rhee@gmail.com NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER THORACIC SOC PI NEW YORK PA 25 BROADWAY, 18 FL, NEW YORK, NY 10004 USA SN 1073-449X EI 1535-4970 J9 AM J RESP CRIT CARE JI Am. J. Respir. Crit. Care Med. PY 2016 VL 193 MA A2739 PG 1 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA EG0VE UT WOS:000390749601879 ER PT J AU Sakoda, L Minowada, G Mogel, G Lee, V Gordon, N Doria-Rose, P Kushi, L Habel, L AF Sakoda, L. Minowada, G. Mogel, G. Lee, V. Gordon, N. Doria-Rose, P. Kushi, L. Habel, L. TI Using Electronic Health Records To Assess Eligibility For Lung Cancer Screening: An Examination Of Capture And Reliability Of Smoking History Data SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Meeting Abstract CT International Conference of the American-Thoracic-Society (ATS) CY MAY 13-18, 2016 CL San Francisco, CA SP Amer Thorac Soc C1 [Sakoda, L.; Lee, V.; Gordon, N.; Habel, L.] Kaiser Permanente Northern Calif, Oakland, CA USA. [Minowada, G.] Kaiser Permanente Northern Calif, Vallejo, CA USA. [Mogel, G.] Kaiser Permanente Northern Calif, Modesto, CA USA. [Doria-Rose, P.] NCI, Rockville, MD USA. EM lori.sakoda@kp.org NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER THORACIC SOC PI NEW YORK PA 25 BROADWAY, 18 FL, NEW YORK, NY 10004 USA SN 1073-449X EI 1535-4970 J9 AM J RESP CRIT CARE JI Am. J. Respir. Crit. Care Med. PY 2016 VL 193 MA A6177 PG 1 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA EG0VE UT WOS:000390749605837 ER PT J AU Salo, PM Wilkerson, J Cohn, RD Zeldin, DC AF Salo, P. M. Wilkerson, J. Cohn, R. D. Zeldin, D. C. TI Atopy In Relation To Endotoxin And Fungal Exposures In Early Life: Results From The National Health And Nutrition Examination Survey 2005-2006 SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Meeting Abstract CT International Conference of the American-Thoracic-Society (ATS) CY MAY 13-18, 2016 CL San Francisco, CA SP Amer Thorac Soc C1 [Salo, P. M.; Zeldin, D. C.] NIEHS, NIH, POB 12233, Res Triangle Pk, NC 27709 USA. [Wilkerson, J.; Cohn, R. D.] Social & Sci Syst Inc, Durham, NC USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU AMER THORACIC SOC PI NEW YORK PA 25 BROADWAY, 18 FL, NEW YORK, NY 10004 USA SN 1073-449X EI 1535-4970 J9 AM J RESP CRIT CARE JI Am. J. Respir. Crit. Care Med. PY 2016 VL 193 MA A7933 PG 1 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA EG0VE UT WOS:000390749608022 ER PT J AU Sato, T Nakashima, K Shibata, Y Ushio, R Ikeda, M Watanabe, H Nagai, K Tashiro, K Nagakura, H Horita, N Yamamoto, M Shinkai, M Kudo, M Klinman, D Kaneko, T AF Sato, T. Nakashima, K. Shibata, Y. Ushio, R. Ikeda, M. Watanabe, H. Nagai, K. Tashiro, K. Nagakura, H. Horita, N. Yamamoto, M. Shinkai, M. Kudo, M. Klinman, D. Kaneko, T. TI Toll-Like Receptor 9, A Key To Attenuation Of Disease Progression In A Mouse Model Of Chronic Obstructive Pulmonary Disease SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Meeting Abstract CT International Conference of the American-Thoracic-Society (ATS) CY MAY 13-18, 2016 CL San Francisco, CA SP Amer Thorac Soc C1 [Sato, T.; Nakashima, K.; Shibata, Y.; Ushio, R.; Ikeda, M.; Watanabe, H.; Nagai, K.; Tashiro, K.; Nagakura, H.; Horita, N.; Yamamoto, M.; Kaneko, T.] Yokohama City Univ, Grad Sch Med, Yokohama, Kanagawa, Japan. [Shinkai, M.; Kudo, M.] Yokohama City Univ, Med Ctr, Yokohama, Kanagawa, Japan. [Klinman, D.] NIH, Frederick, MD USA. EM satotak@yokohama-cu.ac.jp NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER THORACIC SOC PI NEW YORK PA 25 BROADWAY, 18 FL, NEW YORK, NY 10004 USA SN 1073-449X EI 1535-4970 J9 AM J RESP CRIT CARE JI Am. J. Respir. Crit. Care Med. PY 2016 VL 193 MA A6324 PG 1 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA EG0VE UT WOS:000390749606096 ER PT J AU Spaulding, AB Lai, Y Olivier, KN Zelazny, A Kadri, SS Prevots, DR Adjemian, J AF Spaulding, A. B. Lai, Y. Olivier, K. N. Zelazny, A. Kadri, S. S. Prevots, D. R. Adjemian, J. TI Prevalence Of Nontuberculous Mycobacterial Infections Among Patients At 151 Us Hospitals, 2009-2013 SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Meeting Abstract CT International Conference of the American-Thoracic-Society (ATS) CY MAY 13-18, 2016 CL San Francisco, CA SP Amer Thorac Soc C1 [Spaulding, A. B.; Lai, Y.; Zelazny, A.; Prevots, D. R.; Adjemian, J.] NIAID, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA. [Olivier, K. N.] NHLBI, Bldg 10, Bethesda, MD 20892 USA. [Kadri, S. S.] NIH, Ctr Clin, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER THORACIC SOC PI NEW YORK PA 25 BROADWAY, 18 FL, NEW YORK, NY 10004 USA SN 1073-449X EI 1535-4970 J9 AM J RESP CRIT CARE JI Am. J. Respir. Crit. Care Med. PY 2016 VL 193 MA A3014 PG 1 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA EG0VE UT WOS:000390749602262 ER PT J AU Suffredini, DA Cui, X Li, Y Fitz, Y Eichacker, P AF Suffredini, D. A. Cui, X. Li, Y. Fitz, Y. Eichacker, P. TI Hydrocortisone Treatment Decreases Nitric Oxide Levels And Increases Blood Pressure And Survival Following B. Anthracis Cell Wall Peptidoglycan Challenge In Rats SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Meeting Abstract CT International Conference of the American-Thoracic-Society (ATS) CY MAY 13-18, 2016 CL San Francisco, CA SP Amer Thorac Soc C1 [Suffredini, D. A.; Cui, X.; Li, Y.; Fitz, Y.; Eichacker, P.] NIH, Bldg 10, Bethesda, MD 20892 USA. EM dante.suffredini@nih.gov NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER THORACIC SOC PI NEW YORK PA 25 BROADWAY, 18 FL, NEW YORK, NY 10004 USA SN 1073-449X EI 1535-4970 J9 AM J RESP CRIT CARE JI Am. J. Respir. Crit. Care Med. PY 2016 VL 193 MA A2728 PG 1 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA EG0VE UT WOS:000390749601868 ER PT J AU Sullivan, KM Daniels, M Atkinson, JJ Ferkol, TW Hall, D Lee, HS Metjian, H Olivier, KN Rosenfeld, M Milla, CE Zariwala, M Sagel, SD Carson, J Krischer, J Hazucha, M Knowles, M Leigh, M AF Sullivan, K. M. Daniels, M. Atkinson, J. J. Ferkol, T. W. Hall, D. Lee, H. -S. Metjian, H. Olivier, K. N. Rosenfeld, M. Milla, C. E. Zariwala, M. Sagel, S. D. Carson, J. Krischer, J. Hazucha, M. Knowles, M. Leigh, M. CA GDMCC TI Clinical Features And Associated Likelihood Of Primary Ciliary Dyskinesia In Adults SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Meeting Abstract CT International Conference of the American-Thoracic-Society (ATS) CY MAY 13-18, 2016 CL San Francisco, CA SP Amer Thorac Soc C1 [Sullivan, K. M.; Daniels, M.; Metjian, H.; Zariwala, M.; Carson, J.; Hazucha, M.; Knowles, M.; Leigh, M.; GDMCC] Univ N Carolina, Chapel Hill, NC USA. [Atkinson, J. J.; Ferkol, T. W.] Washington Univ, Sch Med, St Louis, MO USA. [Hall, D.] St Michaels Univ, Toronto, ON, Canada. [Lee, H. -S.; Krischer, J.] Univ S Florida, Tampa, FL USA. [Olivier, K. N.] NHLBI, Bldg 10, Bethesda, MD 20892 USA. [Rosenfeld, M.] Seattle Childrens Hosp, Seattle, WA USA. [Milla, C. E.] Stanford Univ, Sch Med, Packard Childrens Hosp Stanford, Palo Alto, CA 94304 USA. [Sagel, S. D.] Univ Colorado, Aurora, CO USA. EM kelli_sullivan@med.unc.edu NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER THORACIC SOC PI NEW YORK PA 25 BROADWAY, 18 FL, NEW YORK, NY 10004 USA SN 1073-449X EI 1535-4970 J9 AM J RESP CRIT CARE JI Am. J. Respir. Crit. Care Med. PY 2016 VL 193 MA A1765 PG 1 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA EG0VE UT WOS:000390749600764 ER PT J AU Taveira-DaSilva, AM Julien-Williams, P Jones, AM Haughey, M Stylianou, M Moss, J AF Taveira-DaSilva, A. M. Julien-Williams, P. Jones, A. M. Haughey, M. Stylianou, M. Moss, J. TI Reproducibility Of Fev1 Measurements In Patients With Lymphangioleiomyomatosis SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Meeting Abstract CT International Conference of the American-Thoracic-Society (ATS) CY MAY 13-18, 2016 CL San Francisco, CA SP Amer Thorac Soc C1 [Taveira-DaSilva, A. M.; Julien-Williams, P.; Jones, A. M.; Haughey, M.; Moss, J.] NIH, Bldg 10, Bethesda, MD 20892 USA. [Stylianou, M.] NHLBI, NIH, Bldg 10, Bethesda, MD 20892 USA. EM dasilvaa@nhlbi.nih.gov NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER THORACIC SOC PI NEW YORK PA 25 BROADWAY, 18 FL, NEW YORK, NY 10004 USA SN 1073-449X EI 1535-4970 J9 AM J RESP CRIT CARE JI Am. J. Respir. Crit. Care Med. PY 2016 VL 193 MA A6257 PG 1 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA EG0VE UT WOS:000390749606029 ER PT J AU Taveira-DaSilva, AM Jones, AM Julien-Williams, P Yao, J Moss, J AF Taveira-DaSilva, A. M. Jones, A. M. Julien-Williams, P. Yao, J. Moss, J. TI Tracheobronchomegaly In Mounier-Kuhn Syndrome Mimicking The Cystic Lung Disease Seen In Lymphangioleiomyomatosis SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Meeting Abstract CT International Conference of the American-Thoracic-Society (ATS) CY MAY 13-18, 2016 CL San Francisco, CA SP Amer Thorac Soc C1 [Taveira-DaSilva, A. M.; Jones, A. M.; Julien-Williams, P.; Yao, J.; Moss, J.] NIH, Bldg 10, Bethesda, MD 20892 USA. EM dasilvaa@nhlbi.nih.gov NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER THORACIC SOC PI NEW YORK PA 25 BROADWAY, 18 FL, NEW YORK, NY 10004 USA SN 1073-449X EI 1535-4970 J9 AM J RESP CRIT CARE JI Am. J. Respir. Crit. Care Med. PY 2016 VL 193 MA A5085 PG 1 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA EG0VE UT WOS:000390749604599 ER PT J AU Vayntrub, Y Seam, N Avila, NA Mobarek, D AF Vayntrub, Y. Seam, N. Avila, N. A. Mobarek, D. TI Appropriate Ordering Of Computed Tomography Pulmonary Angiograms To Evaluate For Pulmonary Embolism SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Meeting Abstract CT International Conference of the American-Thoracic-Society (ATS) CY MAY 13-18, 2016 CL San Francisco, CA SP Amer Thorac Soc C1 [Vayntrub, Y.] George Washington Univ, Washington, DC USA. [Seam, N.] NIH, Bldg 10, Bethesda, MD 20892 USA. [Avila, N. A.; Mobarek, D.] Washington DC Vet Affairs Med Ctr, Washington, DC USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER THORACIC SOC PI NEW YORK PA 25 BROADWAY, 18 FL, NEW YORK, NY 10004 USA SN 1073-449X EI 1535-4970 J9 AM J RESP CRIT CARE JI Am. J. Respir. Crit. Care Med. PY 2016 VL 193 MA A5717 PG 1 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA EG0VE UT WOS:000390749605379 ER PT J AU Wills, AB Fontana, JR Steiner, CA Ackerman, HC Ruhl, AP Olivier, KN Prevots, DR AF Wills, A. B. Fontana, J. R. Steiner, C. A. Ackerman, H. C. Ruhl, A. P. Olivier, K. N. Prevots, D. R. TI Sarcoidosis-Associated Hospitalizations In The United States, 2002-2012 SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Meeting Abstract CT International Conference of the American-Thoracic-Society (ATS) CY MAY 13-18, 2016 CL San Francisco, CA SP Amer Thorac Soc C1 [Wills, A. B.; Prevots, D. R.] NIAID, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA. [Fontana, J. R.; Ackerman, H. C.; Ruhl, A. P.; Olivier, K. N.] NHLBI, NIH, Bldg 10, Bethesda, MD 20892 USA. [Steiner, C. A.] Agcy Healthcare Qual & Res, Rockville, MD USA. EM aprielle.wills@nih.gov NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER THORACIC SOC PI NEW YORK PA 25 BROADWAY, 18 FL, NEW YORK, NY 10004 USA SN 1073-449X EI 1535-4970 J9 AM J RESP CRIT CARE JI Am. J. Respir. Crit. Care Med. PY 2016 VL 193 MA A2952 PG 2 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA EG0VE UT WOS:000390749602200 ER PT J AU Xu, J Bartz, TM Chittoor, G Eiriksdottir, G Frazier-Wood, AC Lahousse, L Latourelle, J Manichaikul, AW Sun, F Terzikhan, N Barr, RG Brusselle, GG Dupuis, J Gharib, SA London, S North, KE Psaty, B Smith, A Hancock, DB Cassano, PA AF Xu, J. Bartz, T. M. Chittoor, G. Eiriksdottir, G. Frazier-Wood, A. C. Lahousse, L. Latourelle, J. Manichaikul, A. W. Sun, F. Terzikhan, N. Barr, R. G. Brusselle, G. G. Dupuis, J. Gharib, S. A. London, S. North, K. E. Psaty, B. Smith, A. Hancock, D. B. Cassano, P. A. TI Meta-Analysis Of The Association Of Serum Vitamin D With Pulmonary Function SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Meeting Abstract CT International Conference of the American-Thoracic-Society (ATS) CY MAY 13-18, 2016 CL San Francisco, CA SP Amer Thorac Soc C1 [Bartz, T. M.; Gharib, S. A.; Psaty, B.] Univ Washington, Seattle, WA 98195 USA. [Chittoor, G.; North, K. E.] Univ N Carolina, Chapel Hill, NC USA. [Eiriksdottir, G.; Smith, A.] Iceland Heart Assoc, Kopavogur, Iceland. [Frazier-Wood, A. C.] Baylor Coll Med, Houston, TX 77030 USA. [Lahousse, L.; Terzikhan, N.; Brusselle, G. G.] Univ Ghent, Ghent, Belgium. [Lahousse, L.] Boston Univ, Sch Med, Boston, MA 02118 USA. [Manichaikul, A. W.] Univ Virginia, Sch Med, Charlottesville, VA 22908 USA. [Sun, F.; Dupuis, J.] Boston Univ, Boston, MA 02215 USA. [Barr, R. G.] Columbia Univ, New York, NY USA. [London, S.] NIEHS, NIH, DHHS, POB 12233, Res Triangle Pk, NC 27709 USA. [Hancock, D. B.] RTI Int, Res Triangle Pk, NC USA. EM jx99@cornell.edu NR 0 TC 0 Z9 0 U1 1 U2 1 PU AMER THORACIC SOC PI NEW YORK PA 25 BROADWAY, 18 FL, NEW YORK, NY 10004 USA SN 1073-449X EI 1535-4970 J9 AM J RESP CRIT CARE JI Am. J. Respir. Crit. Care Med. PY 2016 VL 193 MA A2776 PG 1 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA EG0VE UT WOS:000390749602025 ER PT J AU Yoon, J Bertero, T Cottrill, KA Annis, S Bhat, B Gochuico, B Osorio, JC Rosas, IO Haley, KJ Chau, B Chan, SY AF Yoon, J. Bertero, T. Cottrill, K. A. Annis, S. Bhat, B. Gochuico, B. Osorio, J. C. Rosas, I. O. Haley, K. J. Chau, B. Chan, S. Y. TI A Systems-Biology Approach To Identify A Yap/taz-Mir-130/301 Molecular Circuit Controlling Pulmonary Fibrosis SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Meeting Abstract CT International Conference of the American-Thoracic-Society (ATS) CY MAY 13-18, 2016 CL San Francisco, CA SP Amer Thorac Soc C1 [Yoon, J.; Chan, S. Y.] Univ Pittsburgh, Pittsburgh, PA USA. [Bertero, T.] Univ Nice Sophia Antipolis, Nice, France. [Cottrill, K. A.; Annis, S.; Rosas, I. O.; Haley, K. J.] Brigham & Womens Hosp, 75 Francis St, Boston, MA 02115 USA. [Bhat, B.; Chau, B.] Regulus Therapeut, San Diego, CA USA. [Gochuico, B.] NHGRI, Bethesda, MD 20892 USA. [Osorio, J. C.] NewYork Presbyterian Hosp, Weill Cornell Med Coll, New York, NY USA. EM yoonjh@upmc.edu NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER THORACIC SOC PI NEW YORK PA 25 BROADWAY, 18 FL, NEW YORK, NY 10004 USA SN 1073-449X EI 1535-4970 J9 AM J RESP CRIT CARE JI Am. J. Respir. Crit. Care Med. PY 2016 VL 193 MA A4614 PG 1 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA EG0VE UT WOS:000390749604130 ER PT J AU Zamanian, RT Rhee, R Pinckney, A Goldmuntz, E Welch, B D'Aveta, C Badesch, D Nicolls, M Kawut, SM Spychala, M AF Zamanian, R. T. Rhee, R. Pinckney, A. Goldmuntz, E. Welch, B. D'Aveta, C. Badesch, D. Nicolls, M. Kawut, S. M. Spychala, M. CA Autoimmunity Ctr Excellence ASC01 TI Limitations Of Pulmonary Vascular Resistance As A Primary Endpoint For Therapeutic Trials Of Systemic Sclerosis Associated Pulmonary Arterial Hypertension SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Meeting Abstract CT International Conference of the American-Thoracic-Society (ATS) CY MAY 13-18, 2016 CL San Francisco, CA SP Amer Thorac Soc C1 [Zamanian, R. T.; Nicolls, M.] Stanford Univ, Stanford, CA 94305 USA. [Rhee, R.] Univ Penn, Philadelphia, PA 19104 USA. [Pinckney, A.; D'Aveta, C.; Spychala, M.] Rho, Chapel Hill, NC USA. [Goldmuntz, E.; Welch, B.] NIAID, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA. [Badesch, D.] Univ Colorado, Denver, CO 80202 USA. [Kawut, S. M.] Univ Penn, Sch Med, Philadelphia, PA 19104 USA. EM roham.zamanian@stanford.edu NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER THORACIC SOC PI NEW YORK PA 25 BROADWAY, 18 FL, NEW YORK, NY 10004 USA SN 1073-449X EI 1535-4970 J9 AM J RESP CRIT CARE JI Am. J. Respir. Crit. Care Med. PY 2016 VL 193 MA A7366 PG 2 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA EG0VE UT WOS:000390749607302 ER PT J AU Zhou, Y He, CH Herzog, E Peng, X Lee, CM Nguyen, T Gulati, M Gochuico, B Gahl, W Slade, M Lee, CG Elias, JA AF Zhou, Y. He, C. H. Herzog, E. Peng, X. Lee, C. -M. Nguyen, T. Gulati, M. Gochuico, B. Gahl, W. Slade, M. Lee, C. G. Elias, J. A. TI Chitinase 3-Like-1 And Its Receptors In Hermansky-Pudlak Syndrome-Associated Lung Disease SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Meeting Abstract CT International Conference of the American-Thoracic-Society (ATS) CY MAY 13-18, 2016 CL San Francisco, CA SP Amer Thorac Soc C1 [Zhou, Y.; He, C. H.; Lee, C. -M.; Nguyen, T.; Lee, C. G.; Elias, J. A.] Brown Univ, Providence, RI 02912 USA. [Herzog, E.; Peng, X.; Gulati, M.] Yale Univ, New Haven, CT USA. [Gochuico, B.; Gahl, W.] NHGRI, Bethesda, MD 20892 USA. [Slade, M.] Yale Univ, Sch Med, New Haven, CT USA. EM yang_zhou@brown.edu NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER THORACIC SOC PI NEW YORK PA 25 BROADWAY, 18 FL, NEW YORK, NY 10004 USA SN 1073-449X EI 1535-4970 J9 AM J RESP CRIT CARE JI Am. J. Respir. Crit. Care Med. PY 2016 VL 193 MA A2396 PG 1 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA EG0VE UT WOS:000390749601536 ER PT J AU Jin, X Kruth, HS AF Jin, X. Kruth, H. S. BE Lewis, BS Borer, JS Halon, DA TI Function of ABCA1 and ABCG1 in extracellular cholesterol deposition by macrophages SO CORONARY ARTERY DISEASE 2015 LA English DT Proceedings Paper CT 11th International Congress on Coronary Artery Disease (ICCAD) CY NOV 29-DEC 02, 2015 CL Florence, ITALY SP Assoc Nazl Med Cardiologi Ospedalieri, Int Acad Cardiovascular Sci DE reverse cholesterol transport; HDL; atherosclerosis; ABCA1; ABCG1; LXR; probucol ID HIGH-DENSITY-LIPOPROTEIN; MEMBRANE-LIPID DOMAINS; CELLULAR CHOLESTEROL; PLASMA-MEMBRANE; UNESTERIFIED CHOLESTEROL; ATHEROSCLEROTIC LESIONS; ANTIBODY RECOGNITION; FOAM CELLS; EFFLUX; TRANSPORT AB Atherosclerotic plaques contain cholesterol in both intracellular and extracellular forms. However, the origin and fate of extracellular cholesterol in plaques is far less understood compared with intracellular cholesterol. ABCA1 and ABCG1 are two proteins that mediate cholesterol efflux from macrophages. The aim of our study was to determine whether these proteins also function in macrophage deposition of cholesterol into the extracellular matrix. Deposition of cholesterol into the extracellular matrix by cholesterol-loaded macrophages was detected using a unique monoclonal antibody, which labels lipid particles enriched with unesterified cholesterol. LXR is a transcription factor that upregulates gene expression of ABCA1 and ABCG1, and probucol is an inhibitor of ABCA1. The LXR agonist, TO901317 increased and probucol inhibited macrophage deposition of cholesterol into the extracellular matrix, consistent with ABCA1 functioning in extracellular cholesterol deposition. Studies of macrophage extracellular cholesterol deposition by ABCG1 and ABCA1-deficient mouse macrophages showed that both ABCA1 and ABCG1 mediate macrophage deposition of cholesterol into the extracellular matrix. The extracellular cholesterol deposits can be mobilized by cholesterol acceptors such as HDL, thus linking these extracellular cholesterol deposits with the reverse cholesterol transport pathway. Macrophages not only clear their excess unesterified cholesterol by cholesterol esterification and storage within lipid droplets, but also by depositing this excess cholesterol within the extracellular matrix, a process that depends on ABCA1 and ABCG1. Because buildup of excess unesterified cholesterol within cells can be cytotoxic, extracellular deposition of cholesterol represents another means by which macrophages maintain cholesterol homeostasis. C1 [Jin, X.; Kruth, H. S.] NHLBI, Sect Expt Atherosclerosis, NIH, Bldg 10, Bethesda, MD 20892 USA. RP Jin, X (reprint author), NHLBI, Sect Expt Atherosclerosis, NIH, Bldg 10, Bethesda, MD 20892 USA. EM tina.jin@nih.gov; kruthh@nhlbi.nih.gov NR 44 TC 0 Z9 0 U1 0 U2 0 PU MEDIMOND S R L PI 40128 BOLOGNA PA VIA MASERATI 5, 40128 BOLOGNA, 00000, ITALY BN 978-88-7587-729-3 PY 2016 BP 7 EP 11 PG 5 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA BG7DH UT WOS:000391237200002 ER PT J AU Richards, MN Calvert, SL AF Richards, Melissa N. Calvert, Sandra L. TI Parent versus child report of young children's parasocial relationships in the United States SO JOURNAL OF CHILDREN AND MEDIA LA English DT Article DE Parasocial relationships; media characters; parent survey; child interview; young children ID PARA-SOCIAL INTERACTION; TELEVISION CHARACTERS; VIDEO; IDENTIFICATION; ATTACHMENT; REALITY AB This study examines parent perceptions of their young children's one-sided, emotionally tinged relationships with media characters, also known as parasocial relationships (PSR). Prior research has collected data on young children's PSR by surveying parents, while other studies have relied directly on child interview. The current study is the first to compare children's answers to those of their parents. Factor analyses revealed that parents and children both reported three components of children's PSR: social realism, attachment and character personification (parents) or attachment and friendship (for their children), and humanlike needs. Both parent and child reports accounted for approximately 60% of the variance in children's PSR. Nonetheless, only approximately one-third of parents and children reported on the same favorite character. The implications for research on children's PSR using both parent and child reports are discussed. C1 [Richards, Melissa N.; Calvert, Sandra L.] Georgetown Univ, Childrens Digital Media Ctr, Washington, DC 20057 USA. [Richards, Melissa N.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, NIH, Bethesda, MD 20892 USA. RP Richards, MN (reprint author), Georgetown Univ, Childrens Digital Media Ctr, Washington, DC 20057 USA.; Richards, MN (reprint author), Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, NIH, Bethesda, MD 20892 USA. EM melissa.richards@nih.gov FU National Science Foundation [0623871, 1251745]; Georgetown University FX This work was supported by the National Science Foundation [grant number NSF #0623871], [grant number NSF# 1251745] as well as an internal faculty research grant from Georgetown University to Dr. Sandra L. Calvert. NR 44 TC 0 Z9 0 U1 0 U2 0 PU ROUTLEDGE JOURNALS, TAYLOR & FRANCIS LTD PI ABINGDON PA 2-4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXON, ENGLAND SN 1748-2798 EI 1748-2801 J9 J CHILD MEDIA JI J. Child. Media PY 2016 VL 10 IS 4 BP 462 EP 480 DI 10.1080/17482798.2016.1157502 PG 19 WC Communication SC Communication GA EG4UB UT WOS:000391038100005 ER PT S AU Nguyen, C Havlicek, J Duong, Q Vesely, S Gress, R Lindenberg, L Choyke, P Chakrabarty, JH Williams, K AF Chuong Nguyen Havlicek, Joseph Duong, Quyen Vesely, Sara Gress, Ronald Lindenberg, Liza Choyke, Peter Chakrabarty, Jennifer Holter Williams, Kirsten GP IEEE TI AN AUTOMATIC 3D CT/PET SEGMENTATION FRAMEWORK FOR BONE MARROW PROLIFERATION ASSESSMENT SO 2016 IEEE INTERNATIONAL CONFERENCE ON IMAGE PROCESSING (ICIP) SE IEEE International Conference on Image Processing ICIP LA English DT Proceedings Paper CT 23rd IEEE International Conference on Image Processing (ICIP) CY SEP 25-28, 2016 CL Phoenix, AZ SP Inst Elect & Elect Engineers, Inst Elect & Elect Engineers, Signal Proc Soc DE bone segmentation; bone marrow extraction; CT/PET imaging ID IN-VIVO; PET AB Clinical assessment of bone marrow is limited by an inability to evaluate the marrow space comprehensively and dynamically and there is no current method for automatically assessing hematopoietic activity within the medullary space. Evaluating the hematopoietic space in its entirety could be applicable in blood disorders, malignancies, infections, and medication toxicity. In this paper, we introduce a CT/PET 3D automatic framework for measurement of the hematopoietic compartment proliferation within osseous sites. We first perform a full-body bone structure segmentation using 3D graph-cut on the CT volume. The vertebrae are segmented by detecting the discs between adjacent vertebrae. Finally, we register the bone marrow CT volume with its corresponding PET volume and capture the spinal bone marrow volume. The proposed framework was tested on 17 patients, achieving an average accuracy of 86.37% and a worst case accuracy of 82.3% in automatically extracting the aggregate volume of the spinal marrow cavities. C1 [Chuong Nguyen; Havlicek, Joseph] Univ Oklahoma, Sch Elect & Comp Engn, Norman, OK 73019 USA. [Duong, Quyen; Vesely, Sara] Univ Oklahoma, Hlth Sci Ctr, Dept Biostat & Epidemiol, Norman, OK 73019 USA. [Gress, Ronald; Williams, Kirsten] Natl Canc Inst, Expt Transplantat & Immunol Branch, NIH, Bethesda, MD USA. [Lindenberg, Liza; Choyke, Peter] NIH, Mol Imaging Branch, Bethesda, MD USA. [Chakrabarty, Jennifer Holter] Univ Oklahoma, Hlth Sci Ctr, Dept Med Hematol Oncol, Norman, OK 73019 USA. [Williams, Kirsten] Childrens Natl Hlth Syst, Childrens Res Inst, Washington, DC USA. RP Nguyen, C (reprint author), Univ Oklahoma, Sch Elect & Comp Engn, Norman, OK 73019 USA. NR 18 TC 0 Z9 0 U1 0 U2 0 PU IEEE PI NEW YORK PA 345 E 47TH ST, NEW YORK, NY 10017 USA SN 1522-4880 BN 978-1-4673-9961-6 J9 IEEE IMAGE PROC PY 2016 BP 4126 EP 4130 PG 5 WC Engineering, Electrical & Electronic; Imaging Science & Photographic Technology SC Engineering; Imaging Science & Photographic Technology GA BG6QD UT WOS:000390782004025 ER PT J AU Xiang, Y Yao, XH Chen, KQ Wang, XF Zhou, JM Gong, WH Yoshimura, T Huang, JQ Wang, RQ Wu, YZ Shi, GC Bian, XW Wang, JM AF Xiang, Yi Yao, Xiaohong Chen, Keqiang Wang, Xiafei Zhou, Jiamin Gong, Wanghua Yoshimura, Teizo Huang, Jiaqiang Wang, Rongquan Wu, Yuzhang Shi, Guochao Bian, Xiuwu Wang, Jiming TI The G-protein coupled chemoattractant receptor FPR2 promotes malignant phenotype of human colon cancer cells SO AMERICAN JOURNAL OF CANCER RESEARCH LA English DT Article DE Colon; cancer; FPR2; tumorigenesis; prognosis ID FORMYL PEPTIDE RECEPTOR; HUMAN GLIOBLASTOMA CELLS; FORMYLPEPTIDE RECEPTOR; CHEMOTACTIC AGONIST; HOST-DEFENSE; ACTIVATION; GROWTH; IDENTIFICATION; RESTITUTION; PATHWAY AB The G-protein coupled chemoattractant receptor formylpeptide receptor-2 (FPR2 in human, Fpr2 in mice) is expressed by mouse colon epithelial cells and plays a critical role in mediating mucosal homeostasis and inflammatory responses. However, the biological role of FPR2 in human colon is unclear. Our investigation revealed that a considerable number of human colon cancer cell lines expressed FPR2 and its ligands promoted cell migration and proliferation. Human colon cancer cell lines expressing high levels of FPR2 also formed more rapidly growing tumors in immunocompromised mice as compared with cell lines expressing lower levels of FPR2. Knocking down of FPR2 from colon cancer cell lines highly expressing FPR2 reduced their tumorigenicity. Clinically, FPR2 is more highly expressed in progressive colon cancer, associated with poorer patient prognosis. These results suggest that FPR2 can be high-jacked by colon cancer cells for their growth advantage, thus becoming a potential target for therapeutic development. C1 [Xiang, Yi; Wang, Xiafei; Shi, Guochao] Shanghai Jiao Tong Univ, Sch Med, Rui Jin Hosp, Dept Pulm Med, Shanghai 200025, Peoples R China. [Xiang, Yi; Chen, Keqiang; Wang, Xiafei; Zhou, Jiamin; Yoshimura, Teizo; Wang, Jiming] NCI, Canc & Inflammat Program, Ctr Canc Res, Frederick, MD 21702 USA. [Yao, Xiaohong; Bian, Xiuwu] Third Mil Med Univ, Inst Pathol, Chongqing 400038, Peoples R China. [Yao, Xiaohong; Bian, Xiuwu] Third Mil Med Univ, Southwest Canc Ctr, Chongqing 400038, Peoples R China. [Zhou, Jiamin] Fudan Univ, Shanghai Canc Ctr, Dept Liver Surg, Shanghai 200032, Peoples R China. [Gong, Wanghua] Leidos Biomed Res Inc, Basic Res Program, Frederick, MD 21702 USA. [Huang, Jiaqiang] Beijing Jiaotong Univ, Sch Sci, Coll Life Sci & Bioengn, Beijing 100044, Peoples R China. [Wang, Rongquan] Third Mil Med Univ, Southwest Hosp, Dept Gastroenterol, Chongqing 400038, Peoples R China. [Wu, Yuzhang] Third Mil Med Univ, Inst Immunol, Chongqing 400038, Peoples R China. RP Wang, JM (reprint author), NCI, Canc & Inflammat Program, Ctr Canc Res, Frederick, MD 21702 USA.; Bian, XW (reprint author), Third Mil Med Univ, Inst Pathol, Chongqing 400038, Peoples R China.; Bian, XW (reprint author), Third Mil Med Univ, Southwest Canc Ctr, Chongqing 400038, Peoples R China. EM bianxiuwu@263.net; wangji@mail.nih.gov RI Bian, Xiu-wu/D-4736-2017 OI Bian, Xiu-wu/0000-0003-4383-0197 FU National Cancer Institute, National Institutes of Health [HHSN261200800-001E]; Intramural Research Program of the NCI, NIH FX The authors thank Dr. A. Tominaga of the Department of Molecule and Cellular Biology, Kochi University, Kochi, Japan for providing FPCK-1-1, a normal human colon epithelial cell line; Dr. J. J. Oppenheim for critically reviewing the manuscript; Ms. C. Lamb and Ms. S. Livingstone for secretarial assistance. This project was funded in part by federal funds from the National Cancer Institute, National Institutes of Health, under Contract No. HHSN261200800-001E and was supported in part by the Intramural Research Program of the NCI, NIH. NR 28 TC 0 Z9 0 U1 0 U2 0 PU E-CENTURY PUBLISHING CORP PI MADISON PA 40 WHITE OAKS LN, MADISON, WI 53711 USA SN 2156-6976 J9 AM J CANCER RES JI Am. J. Cancer Res. PY 2016 VL 6 IS 11 BP 2599 EP + PG 14 WC Oncology SC Oncology GA EF8PO UT WOS:000390591500015 PM 27904774 ER PT J AU Wang, L Hu, G AF Wang, Li Hu, Guang TI Remodeling super-enhancers and oncogenic transcription SO CELL CYCLE LA English DT Editorial Material DE chromatin remodeling; INO80; melanoma; oncogenic transcription; signal integration; super-enhancer ID MELANOMA C1 [Wang, Li] Chinese Acad Med Sci, Natl Ctr Cardiovasc Dis, Fuwai Hosp, State Key Lab Cardiovasc Dis, Beijing, Peoples R China. [Wang, Li] Peking Union Med Coll, Beijing, Peoples R China. [Hu, Guang] Natl Inst Environm Hlth Sci, Epigenet & Stem Cell Biol Lab, Res Triangle Pk, NC 27709 USA. RP Wang, L (reprint author), Chinese Acad Med Sci, Natl Ctr Cardiovasc Dis, Fuwai Hosp, State Key Lab Cardiovasc Dis, Beijing, Peoples R China.; Wang, L (reprint author), Peking Union Med Coll, Beijing, Peoples R China.; Hu, G (reprint author), Natl Inst Environm Hlth Sci, Epigenet & Stem Cell Biol Lab, Res Triangle Pk, NC 27709 USA. EM wangl@pumc.edu.cn; hug4@niehs.nih.gov NR 6 TC 0 Z9 0 U1 1 U2 1 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 PY 2016 VL 15 IS 23 BP 3157 EP 3158 DI 10.1080/15384101.2016.1220715 PG 2 WC Cell Biology SC Cell Biology GA EF9RG UT WOS:000390666700006 PM 27579716 ER PT J AU de Moraes, MC Cardoso, CL Seidl, C Moaddel, R Cass, QB AF de Moraes, Marcela Cristina Cardoso, Carmen Lucia Seidl, Claudia Moaddel, Ruin Cass, Quezia Bezerra TI Targeting Anti-Cancer Active Compounds: Affinity-Based Chromatographic Assays SO CURRENT PHARMACEUTICAL DESIGN LA English DT Review DE Anti-cancer active compounds; screening method; affinity-based chromatography assays ID PERFORMANCE LIQUID-CHROMATOGRAPHY; COATED MAGNETIC BEADS; PURINE NUCLEOSIDE PHOSPHORYLASE; CELL-MEMBRANE CHROMATOGRAPHY; STATIONARY-PHASE CHROMATOGRAPHY; SCREENING ANTITUMOR COMPONENTS; TRADITIONAL CHINESE MEDICINE; FACTOR RECEPTOR ANTAGONISTS; TYROSINE KINASE RECEPTOR; LIGAND-BINDING DOMAIN AB Affinity-based chromatography assays encompass the use of solid supports containing immobilized biological targets to monitor binding events in the isolation, identification and/or characterization of bioactive compounds. This powerful bioanalytical technique allows the screening of potential binders through fast analyses that can be directly performed using isolated substances or complex matrices. An overview of the recent researches in frontal and zonal affinity-based chromatography screening assays, which has been used as a tool in the identification and characterization of new anti-cancer agents, is discussed. In addition, a critical evaluation of the recently emerged ligands fishing assays in complex mixtures is also discussed. C1 [de Moraes, Marcela Cristina] Univ Fed Fluminense, Inst Quim, Dept Quim Organ, BR-24020141 Niteroi, RJ, Brazil. [Cardoso, Carmen Lucia; Seidl, Claudia] Univ Sao Paulo, Fac Filosofia Ciencias & Letras Ribeirao Preto, BR-14040901 Ribeirao Preto, SP, Brazil. [Moaddel, Ruin] NIA, Lab Clin Invest, Div Intramural Res Programs, NIH, Baltimore, MD 21224 USA. [Cass, Quezia Bezerra] Univ Fed Sao Carlos, Dept Quim, Cx Postal 676, BR-13565905 Sao Carlos, SP, Brazil. RP de Moraes, MC (reprint author), Univ Fed Fluminense, Inst Quim, Dept Quim Organ, BR-24020141 Niteroi, RJ, Brazil. EM mcmoraes@id.uff.br RI Cass, Quezia/B-8188-2012; OI Cass, Quezia/0000-0002-6550-1194; Cardoso, Carmen Lucia/0000-0001-6239-6651 FU National Council for Scientific and Technological Development (CNPq); Sao Paulo State Research Foundation (FAPESP) [201301710-1]; Carlos Chagas Filho Foundation for Research Support in the State of Rio de Janeiro (FAPERJ); National Instiute on Aging, NIH FX We would like to thank the National Council for Scientific and Technological Development (CNPq), the Sao Paulo State Research Foundation (FAPESP - Grant 201301710-1) and the Carlos Chagas Filho Foundation for Research Support in the State of Rio de Janeiro (FAPERJ) for the financial support. This work was supported in part by the Intramural Research Progam National Instiute on Aging, NIH (RM). NR 105 TC 1 Z9 1 U1 6 U2 6 PU BENTHAM SCIENCE PUBL LTD PI SHARJAH PA EXECUTIVE STE Y-2, PO BOX 7917, SAIF ZONE, 1200 BR SHARJAH, U ARAB EMIRATES SN 1381-6128 EI 1873-4286 J9 CURR PHARM DESIGN JI Curr. Pharm. Design PY 2016 VL 22 IS 39 BP 5976 EP 5987 DI 10.2174/1381612822666160614080506 PG 12 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA EF9KZ UT WOS:000390650400009 PM 27306095 ER PT J AU Slyepchenko, A Maes, M Machado-Vieira, R Anderson, G Solmi, M Sanz, Y Berk, M Kohler, CA Carvalho, AF AF Slyepchenko, Anastasiya Maes, Michael Machado-Vieira, Rodrigo Anderson, George Solmi, Marco Sanz, Yolanda Berk, Michael Kohler, Cristiano A. Carvalho, Andre F. TI Intestinal Dysbiosis, Gut Hyperpermeability and Bacterial Translocation: Missing Links Between Depression, Obesity and Type 2 Diabetes? SO CURRENT PHARMACEUTICAL DESIGN LA English DT Review DE Microbiome; gut; probiotics; type 2 diabetes mellitus; obesity; metabolic syndrome; major depressive disorder; psychiatry ID NECROSIS-FACTOR-ALPHA; INCREASED OXIDATIVE STRESS; ANXIETY-LIKE BEHAVIOR; C-REACTIVE PROTEIN; CHAIN FATTY-ACIDS; GERM-FREE MICE; IMMUNO-INFLAMMATORY PATHWAYS; NUTRITION EXAMINATION SURVEY; COMMON MENTAL-DISORDERS; GASTRIC BYPASS-SURGERY AB The comorbid prevalence of major depressive disorder (MDD) with obesity and type II diabetes mellitus reflects the existence of a subset of individuals with a complex common pathophysiology and overlapping risk factors. Such comorbid disease presentations imply a number of difficulties, including: decreased treatment responsivity and adherence; altered glycemic control and increased risk of wider medical complications. A number of factors link MDD to metabolic-associated disorders, including: higher rates of shared risk factors such as poor diet and physical inactivity and biological elements including increased inflammation; insulin resistance; oxidative and nitrosative stress; and mitochondrial dysfunction. All of these biological factors have been extensively investigated in the pathophysiology of obesity and type 2 diabetes mellitus as well as MDD. In this review, we aim to: (1) overview the epidemiological links between MDD, obesity and type 2 diabetes mellitus; (2) discuss the role of synergistic neurotoxic effects in MDD comorbid with obesity, and type 2 diabetes mellitus; (3) review evidence of intestinal dysbiosis, leaky gut and increased bacterial translocation, in the pathophysiology of MDD, obesity and type 2 diabetes mellitus; and (4) propose a model in which the gut-brain axis could play a pivotal role in the comorbidity of these disorders. C1 [Slyepchenko, Anastasiya] McMaster Univ, MiNDS, McMaster Integrat Neurosci Discovery & Study, Hamilton, ON, Canada. [Slyepchenko, Anastasiya] St Josephs Healthcare Hamilton, Womens Hlth Concerns Clin, Hamilton, ON, Canada. [Maes, Michael] Chulalongkorn Univ, Dept Psychiat, Fac Med, Bangkok, Thailand. [Maes, Michael; Berk, Michael] Deakin Univ, IMPACT Res Ctr, Geelong, Vic, Australia. [Maes, Michael] Univ Estadual Londrina, Fac Med, Dept Psychiat, Londrina, Brazil. [Maes, Michael] Med Univ Plovdiv, Dept Psychiat, Plovdiv, Bulgaria. [Maes, Michael] Revitalis, Waalre, Netherlands. [Machado-Vieira, Rodrigo] Univ Sao Paulo, Lab Neurosci LIM 27, Dept & Inst Psychiat, Fac Med, BR-05508 Sao Paulo, Brazil. [Machado-Vieira, Rodrigo] NIMH, Expt Therapeut & Pathophysiol Branch, NIH, Bethesda, MD 20892 USA. [Anderson, George] CRC Scotland & London, Eccleston Sq, London, England. [Solmi, Marco] Univ Padua, Dept Neurosci, Padua, Italy. [Solmi, Marco] Mental Hlth Dept, Local Hlth Unit 17, Padua, Italy. [Solmi, Marco] IREM, Inst Clin Res & Educ Med, Padua, Italy. [Sanz, Yolanda] Natl Res Council IATA CSIC, Microbial Ecol Nutr & Hlth Res Unit, Inst Agrochem & Food Technol, Av Agustin Escardino 7, Paterna Valencia 46980, Spain. [Berk, Michael] Univ Melbourne, Dept Psychiat, Florey Inst Neurosci & Mental Hlth, Ctr Youth Mental Hlth, Parkville, Vic, Australia. [Berk, Michael] Univ Melbourne, Orygen Natl Ctr Excellence Youth Mental Hlth, Ctr Youth Mental Hlth, Parkville, Vic, Australia. [Kohler, Cristiano A.; Carvalho, Andre F.] Univ Fed Ceara, Dept Clin Med, Fac Med, Rua Prof Costa Mendes 1608,4 Andar, BR-60430040 Fortaleza, Ceara, Brazil. [Kohler, Cristiano A.; Carvalho, Andre F.] Univ Fed Ceara, Translat Psychiat Res Grp, Fac Med, Fortaleza, Ceara, Brazil. RP Carvalho, AF (reprint author), Univ Fed Ceara, Dept Clin Med, Fac Med, Rua Prof Costa Mendes 1608,4 Andar, BR-60430040 Fortaleza, Ceara, Brazil. EM andrefc7@terra.com.br FU European Union [613979]; Spanish Ministry of Economy and Competitiveness (MINECO, Spain) [AGL2014-52101-P]; NHMRC [1059660]; Conselho Nacional de Desenvolvimento Cientifico e Tecnologico (CNPq; Brazil) FX YS contribution is supported by the European Union's Seventh Framework Program under the grant agreement no 613979 (MyNewGut) and the Spanish Ministry of Economy and Competitiveness (MINECO, Spain) grant AGL2014-52101-P. MB is supported by a NHMRC Senior Principal Research Fellowship 1059660. AFC is supported by a research fellowship award from Conselho Nacional de Desenvolvimento Cientifico e Tecnologico (CNPq; Brazil). NR 329 TC 1 Z9 1 U1 16 U2 16 PU BENTHAM SCIENCE PUBL LTD PI SHARJAH PA EXECUTIVE STE Y-2, PO BOX 7917, SAIF ZONE, 1200 BR SHARJAH, U ARAB EMIRATES SN 1381-6128 EI 1873-4286 J9 CURR PHARM DESIGN JI Curr. Pharm. Design PY 2016 VL 22 IS 40 BP 6087 EP 6106 DI 10.2174/1381612822666160922165706 PG 20 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA EF9LE UT WOS:000390650900004 PM 27669970 ER PT J AU Renner, M Saligan, LN AF Renner, Michael Saligan, Leorey N. TI Understanding cancer-related fatigue: advancing the science SO FATIGUE-BIOMEDICINE HEALTH AND BEHAVIOR LA English DT Editorial Material ID BREAST-CANCER; CHEMOTHERAPY; ASSOCIATION; DEPRESSION; MECHANISMS; THERAPY C1 [Renner, Michael; Saligan, Leorey N.] NINR, NIH, Bethesda, MD 20892 USA. RP Saligan, LN (reprint author), NINR, NIH, Bethesda, MD 20892 USA. EM saliganl@mail.nih.gov FU Division of Intramural Research, National Institute of Nursing Research, National Institutes of Health FX This activity is supported by the Division of Intramural Research, National Institute of Nursing Research, National Institutes of Health. NR 21 TC 0 Z9 0 U1 1 U2 1 PU ROUTLEDGE JOURNALS, TAYLOR & FRANCIS LTD PI ABINGDON PA 2-4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXON, ENGLAND EI 2164-1862 J9 FATIGUE JI FATIGUE PY 2016 VL 4 IS 4 BP 189 EP 192 DI 10.1080/21641846.2016.1246513 PG 4 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA EF9QS UT WOS:000390665300001 ER PT J AU Bah, CSF Bekhit, AEA Fang, EF Ng, TB McConnell, MA Bekhit, AA Morton, JD AF Bah, Clara Shui Fern Bekhit, Alaa El-Din Ahmed Fang, Evandro Fei Ng, Tzi Bun McConnell, Michelle A. Bekhit, Adnan A. Morton, James D. TI Physicochemical Properties and Bioactivity of Extracts from the Roe of New Zealand Hoki and Southern Blue Whiting SO JOURNAL OF AQUATIC FOOD PRODUCT TECHNOLOGY LA English DT Article DE Fish roe; hoki; southern blue whiting; physicochemical; bioactivity ID CYSTEINE PROTEASE INHIBITOR; MERLANGUS-EUXINUS NORDMANN; GALACTOSE-SPECIFIC LECTIN; RHAMNOSE-BINDING LECTIN; PROCESSING BY-PRODUCTS; FRESH FRUITING BODIES; CHINOOK SALMON ROE; ANTIPROLIFERATIVE ACTIVITY; BIOCHEMICAL-PROPERTIES; CHEMICAL-COMPOSITION AB Various physicochemical properties of New Zealand hoki and southern blue whiting (SBW) roes and the biological activities of their extracts were investigated. Protein, moisture, and ash contents in both roes were similar; however, the lipid content of hoki roe was higher (p < 0.05) than SBW roe (11.0 +/- 0.9 and 2.5 +/- 0.1, respectively). Both fish roe extracts contained active protease inhibitors toward trypsin and papain. Neither of the roe extracts agglutinated erythrocytes, indicating the absence of lectins. Both fish roe extracts at 5 mg/mL concentration exhibited slight inhibitory effects on the proliferation of breast cancer cells, but neither of the roe extracts exhibited RNase or antifungal activity. C1 [Bah, Clara Shui Fern; Bekhit, Alaa El-Din Ahmed] Univ Otago, Dept Food Sci, POB 56, Dunedin 9016, New Zealand. [Fang, Evandro Fei] NIA, Lab Mol Gerontol, NIH, Baltimore, MD 21224 USA. [Ng, Tzi Bun] Chinese Univ Hong Kong, Sch Biomed Sci, Fac Med, Shatin, Hong Kong, Peoples R China. [McConnell, Michelle A.] Univ Otago, Dept Microbiol & Immunol, Dunedin, New Zealand. [Bekhit, Adnan A.] Univ Alexandria, Dept Pharmaceut Chem, Fac Pharm, Alexandria, Egypt. [Morton, James D.] Lincoln Univ, Dept Wine Food & Mol Biosci, Canterbury, New Zealand. RP Bekhit, AEA (reprint author), Univ Otago, Dept Food Sci, POB 56, Dunedin 9016, New Zealand. EM aladin.bekhit@otago.ac.nz FU University of Otago Postgraduate Publishing Bursary FX The writing of this article was supported by a University of Otago Postgraduate Publishing Bursary. NR 70 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 1049-8850 EI 1547-0636 J9 J AQUAT FOOD PROD T JI J. Aquat. Food Prod. Technol. PY 2016 VL 25 IS 8 BP 1234 EP 1248 DI 10.1080/10498850.2015.1052604 PG 15 WC Food Science & Technology SC Food Science & Technology GA EF8PF UT WOS:000390590500007 ER PT J AU Phummarin, N Boshoff, HI Tsang, PS Dalton, J Wiles, S Barry, CE Copp, BR AF Phummarin, Narisa Boshoff, Helena I. Tsang, Patricia S. Dalton, James Wiles, Siouxsie Barry, Clifton E., III Copp, Brent R. TI SAR and identification of 2-(quinolin-4yloxy)acetamides as Mycobacterium tuberculosis cytochrome bc(1) inhibitors SO MEDCHEMCOMM LA English DT Article ID DRUG DISCOVERY; SCREEN; LEADS; TB AB A previous phenotypic screen by GSK identified 2-(quinolin-4-yloxy) acetamides as potent growth inhibitors of Mycobacterium tuberculosis (Mtb). We report the results of a preliminary structure-activity relationship (SAR) study of the compound class which has yielded more potent inhibitors. An Mtb cytochrome bd oxidase deletion mutant (cydKO) was found to be hypersensitive to most members of the compound library, while strains carrying single-nucleotide polymorphisms of the qcrB gene, which encodes a subunit of the menaquinol cytochrome c oxidoreductase (bc(1)) complex, were resistant to the library. These results identify that the 2-(quinolin-4-yloxy) acetamide class of Mtb growth inhibitors can be added to the growing number of scaffolds that target the M. tuberculosis bc(1) complex. C1 [Phummarin, Narisa; Copp, Brent R.] Univ Auckland, Sch Chem Sci, Private Bag 92019, Auckland 1142, New Zealand. [Boshoff, Helena I.; Tsang, Patricia S.; Barry, Clifton E., III] NIAID, TB Res Sect, Lab Clin Infect Dis, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA. [Dalton, James; Wiles, Siouxsie] Univ Auckland, Dept Mol Med & Pathol, Bioluminescent Superbugs Lab, Private Bag 92019, Auckland 1142, New Zealand. [Wiles, Siouxsie] Univ Auckland, Te Punaha Matatini, Private Bag 92019, Auckland 1142, New Zealand. RP Copp, BR (reprint author), Univ Auckland, Sch Chem Sci, Private Bag 92019, Auckland 1142, New Zealand. EM b.copp@auckland.ac.nz FU University of Auckland [23563]; Intramural Research Program of NIAID, NIH FX We acknowledge funding from the University of Auckland (including in part from the Vice Chancellors Strategic Development Fund [23563]) and, in part, by the Intramural Research Program of NIAID, NIH. We thank Dr M. Schmitz for assistance with NMR data acquisition, Mr Tony Chen for MS data and V. de Guzman for preliminary studies. NR 19 TC 1 Z9 1 U1 2 U2 2 PU ROYAL SOC CHEMISTRY PI CAMBRIDGE PA THOMAS GRAHAM HOUSE, SCIENCE PARK, MILTON RD, CAMBRIDGE CB4 0WF, CAMBS, ENGLAND SN 2040-2503 EI 2040-2511 J9 MEDCHEMCOMM JI MedChemComm PY 2016 VL 7 IS 11 BP 2122 EP 2127 DI 10.1039/c6md00236f PG 6 WC Biochemistry & Molecular Biology; Chemistry, Medicinal SC Biochemistry & Molecular Biology; Pharmacology & Pharmacy GA EF8AY UT WOS:000390551700008 PM 28337336 ER PT J AU Herdman, CA Strecker, TE Tanpure, RP Chen, Z Winters, A Gerberich, J Liu, L Hamel, E Mason, RP Chaplin, DJ Trawick, ML Pinney, KG AF Herdman, Christine A. Strecker, Tracy E. Tanpure, Rajendra P. Chen, Zhi Winters, Alex Gerberich, Jeni Liu, Li Hamel, Ernest Mason, Ralph P. Chaplin, David J. Trawick, Mary Lynn Pinney, Kevin G. TI Synthesis and biological evaluation of benzocyclooctene-based and indene-based anticancer agents that function as inhibitors of tubulin polymerization SO MEDCHEMCOMM LA English DT Article ID VASCULAR-DISRUPTING AGENTS; COMBRETASTATIN A4 PHOSPHATE; HYPOXIA-ACTIVATED PRODRUG; PHASE-I TRIAL; TUMOR VASCULATURE; ANTINEOPLASTIC AGENTS; BENZOSUBERENE ANALOGS; CELL-PROLIFERATION; TARGETING AGENT; SITE INHIBITORS AB The natural products colchicine and combretastatin A-4 (CA4) have been inspirational for the design and synthesis of structurally related analogues and spin-off compounds as inhibitors of tubulin polymerization. The discovery that a water-soluble phosphate prodrug salt of CA4 (referred to as CA4P) is capable of imparting profound and selective damage to tumor-associated blood vessels paved the way for the development of a new therapeutic approach for cancer treatment utilizing small-molecule inhibitors of tubulin polymerization that also act as vascular disrupting agents (VDAs). Combination of salient structural features associated with colchicine and CA4 led to the design and synthesis of a variety of fused aryl-cycloalkyl and aryl-heterocyclic compounds that function as inhibitors of tubulin polymerization. Prominent among these compounds is a benzosuberene analogue (referred to as KGP18), which demonstrates sub-nM cytotoxicity against human cancer cell lines and functions (when administered as a water-soluble prodrug salt) as a VDA in mouse models. Structure activity relationship considerations led to the evaluation of benzocyclooctyl [6,8 fused] and indene [6,5 fused] ring systems. Four benzocyclooctene and four indene analogues were prepared and evaluated biologically. Three of the benzocyclooctene analogues were active as inhibitors of tubulin polymerization (IC50 < 5 mu M), and benzocyclooctene phenol 23 was comparable to KGP18 in terms of potency. The analogous indene-based compound 31 also functioned as an inhibitor of tubulin polymerization (IC50 = 11 mu M) with reduced potency. The most potent inhibitor of tubulin polymerization from this group was benzocyclooctene analogue 23, and it was converted to its water-soluble prodrug salt 24 to assess its potential as a VDA. Preliminary in vivo studies, which utilized the MCF7-luc-GFP-mCherry breast tumor in a SCID mouse model, demonstrated that treatment with 24 (120 mg kg(-1)) resulted in significant vascular shutdown, as evidenced by bioluminescence imaging at 4 h post administration, and that the effect continued at both 24 and 48 h. Contemporaneous studies with CA4P, a clinically relevant VDA, were carried out as a positive control. C1 [Herdman, Christine A.; Strecker, Tracy E.; Tanpure, Rajendra P.; Chen, Zhi; Chaplin, David J.; Trawick, Mary Lynn; Pinney, Kevin G.] Baylor Univ, Dept Chem & Biochem, One Bear Pl 97348, Waco, TX 76798 USA. [Winters, Alex; Gerberich, Jeni; Liu, Li; Mason, Ralph P.] Univ Texas Southwestern Med Ctr Dallas, Dept Radiol, Prognost Imaging Res Lab, 5323 Harry Hines Blvd, Dallas, TX 75390 USA. [Hamel, Ernest] NCI, Screening Technol Branch, Dev Therapeut Program,NIH, Div Canc Treatment & Diag,Frederick Natl Lab Canc, Frederick, MD 21702 USA. [Chaplin, David J.] Mateon Therapeut Inc, 701 Gateway Blvd,Suite 210, San Francisco, CA 94080 USA. RP Pinney, KG (reprint author), Baylor Univ, Dept Chem & Biochem, One Bear Pl 97348, Waco, TX 76798 USA. EM Kevin_Pinney@baylor.edu FU National Cancer Institute of the National Institutes of Health [5R01CA140674]; Cancer Prevention and Research Institute of Texas (CPRIT) [RP140399]; Mateon Therapeutics, Inc.; National Institutes of Health National Cancer Institute Cancer Center Support Grant [1P30 CA142543]; [1S10RR024757] FX The authors are grateful to the National Cancer Institute of the National Institutes of Health (Grant No. 5R01CA140674 to K. G. P, M. L. T, and R. P. M), the Cancer Prevention and Research Institute of Texas (CPRIT, Grant No. RP140399 to K. G. P., M. L. T., and R. P. M.), and Mateon Therapeutics, Inc. (grant to K. G. P. and M. L. T.) for their financial support of this project. The content is solely the responsibility of the authors and does not necessarily reflect the official views of the National Institutes of Health. The authors would also thank Dr. Craig Moehnke and Dr. Michelle Nemec (Director) for the use of the shared Molecular Biosciences Center at Baylor University, Dr. Alejandro Ramirez (Mass Spectrometry Core Facility, Baylor University) and Dr. Kevin Klausmeyer and Dr. Marissa Penney (X-ray analysis). The authors are grateful to Mr. Jack Littlejohn and Mr. Jake Lofman (Baylor University) for their contributions to the synthesis of certain analogues. John Shelton (JAR Molecular Pathology core, UTSW) prepared the H&E stained sections. Imaging was facilitated with the assistance of resources of the Harold C. Simmons Cancer Center supported through a National Institutes of Health National Cancer Institute Cancer Center Support Grant [Grant 1P30 CA142543], specifically, the Southwestern Small Animal Imaging Resource, and Live Cell Imaging Resource. The IVIS Spectrum was purchased with support of 1S10RR024757. NR 77 TC 0 Z9 0 U1 2 U2 2 PU ROYAL SOC CHEMISTRY PI CAMBRIDGE PA THOMAS GRAHAM HOUSE, SCIENCE PARK, MILTON RD, CAMBRIDGE CB4 0WF, CAMBS, ENGLAND SN 2040-2503 EI 2040-2511 J9 MEDCHEMCOMM JI MedChemComm PY 2016 VL 7 IS 12 BP 2418 EP 2427 DI 10.1039/c6md00459h PG 10 WC Biochemistry & Molecular Biology; Chemistry, Medicinal SC Biochemistry & Molecular Biology; Pharmacology & Pharmacy GA EF8BE UT WOS:000390552300019 PM 28217276 ER PT J AU Kastrin, A Rindflesch, TC Hristovski, D AF Kastrin, Andrej Rindflesch, Thomas C. Hristovski, Dimitar BE Kumar, R Caverlee, J Tong, H TI Evolution of MEDLINE bibliographic database: Preliminary Results SO PROCEEDINGS OF THE 2016 IEEE/ACM INTERNATIONAL CONFERENCE ON ADVANCES IN SOCIAL NETWORKS ANALYSIS AND MINING ASONAM 2016 LA English DT Proceedings Paper CT 8th IEEE/ACM International Conference on Advances in Social Networks Analysis and Mining (ASONAM) CY AUG 18-21, 2016 CL San Francisco, CA SP IEEE, Assoc Comp Machinery, ACM SIGMOD, IEEE Comp Soc, IEEE TCDE, Springer, VEEPIO DE Network analysis; Community evolution; Network evolution; MEDLINE AB In this preliminary work we propose an approach to tracking network communities in time. We describe a methodology to study the dynamics and evolution of the MEDLINE bibliographic database using network-based analysis. We explore how the temporal characteristics of the network can be used to provide insight into the historical evolution of the broad field of biomedicine. C1 [Kastrin, Andrej] Fac Informat Studies, Novo Mesto, Slovenia. [Rindflesch, Thomas C.] Natl Lib Med, Bethesda, MD USA. [Hristovski, Dimitar] Fac Med, Ljubljana, Slovenia. RP Kastrin, A (reprint author), Fac Informat Studies, Novo Mesto, Slovenia. EM andrej.kastrin@guest.arnes.si; trindflesch@mail.nih.gov; dimitar.hristovski@gmail.com NR 6 TC 0 Z9 0 U1 0 U2 0 PU IEEE PI NEW YORK PA 345 E 47TH ST, NEW YORK, NY 10017 USA BN 978-1-5090-2846-7 PY 2016 BP 644 EP 646 PG 3 WC Computer Science, Information Systems; Communication; Computer Science, Interdisciplinary Applications; Social Sciences, Interdisciplinary SC Computer Science; Communication; Social Sciences - Other Topics GA BG6PQ UT WOS:000390760100100 ER PT S AU Tanawongsuwan, P AF Tanawongsuwan, Patrawadee BE Shanmugapriya, B Sengar, JS Weller, K TI Adjective Roles in Estimating a Product Rating in a Product Review SO PROCEEDINGS OF THE 2016 INTERNATIONAL CONFERENCE ON COMMUNICATIONS, INFORMATION MANAGEMENT AND NETWORK SECURITY SE ACSR-Advances in Comptuer Science Research LA English DT Proceedings Paper CT International Conference on Communications, Information Management and Network Security (CIMNS) CY SEP 25-26, 2016 CL Shanghai, PEOPLES R CHINA DE adjectives; text mining; sentiment analysis; natural language processing AB This research work explores consumers' sentiments through written product reviews. Given a piece of product review, a person likely can tell how much the reviewer likes or dislikes the associated product. This likeness can translate into a numeric scale. For example, reading a product review, one can probably guess how many stars (which is a rating, such as, from 1 through 5) are given by the reviewer to the product. Out of hundreds of words in a particular product review, there might be only few key words that are the key estimators of the reviewer's likeness. This research work explores those estimator type of words, particularly adjectives and other non-adjectives acting as an adjective in its context. By nature, adjectives are words that describe, qualify, modify and give more information about other words. This fact hints an idea of using adjectives in a product review as an estimator for reviewer's likeness. Besides those words defined as adjectives by linguistic definition, this work is also interested in other words that might not strictly be adjectives by linguistic definition but play adjective's role in its corresponding context. This paper reports findings from exploration of the relation between adjectives in a product review and its likeness rating. Experiments are performed on a number of product reviews, book reviews to be specific, from an online bookstore. C1 [Tanawongsuwan, Patrawadee] NIDA, Grad Sch Appl Stat, Bangkok, Thailand. RP Tanawongsuwan, P (reprint author), NIDA, Grad Sch Appl Stat, Bangkok, Thailand. NR 25 TC 0 Z9 0 U1 0 U2 0 PU ATLANTIS PRESS PI PARIS PA 29 AVENUE LAVMIERE, PARIS, 75019, FRANCE SN 2352-538X BN 978-94-6252-247-3 J9 ACSR ADV COMPUT PY 2016 VL 47 BP 217 EP 220 PG 4 WC Computer Science, Information Systems; Computer Science, Interdisciplinary Applications; Computer Science, Theory & Methods SC Computer Science GA BG6WI UT WOS:000390854400054 ER PT J AU Weber, KA Heaphy, CM Rohrmann, S Gonzalez, B Bienstock, JL Agurs-Collins, T Platz, EA Meeker, AK AF Weber, Kari A. Heaphy, Christopher M. Rohrmann, Sabine Gonzalez, Beverly Bienstock, Jessica L. Agurs-Collins, Tanya Platz, Elizabeth A. Meeker, Alan K. TI Influence of In Utero Maternal and Neonate Factors on Cord Blood Leukocyte Telomere Length: Clues to the Racial Disparity in Prostate Cancer? SO PROSTATE CANCER LA English DT Article ID BIRTH-WEIGHT; HEALTH-PROFESSIONALS; FETAL ORIGINS; HORMONE CONCENTRATIONS; RISK; DISEASE; MARKERS; GROWTH; SIZE; MEN AB Background. Modifiable factors in adulthood that explain the racial disparity in prostate cancer have not been identified. Because racial differences in utero that may account for this disparity are understudied, we investigated the association of maternal and neonate factors with cord blood telomere length, as a cumulative marker of cell proliferation and oxidative damage, by race. Further, we evaluated whether cord blood telomere length differs by race. Methods. We measured venous umbilical cord blood leukocyte relative telomere length by qPCR in 38 black and 38 white full-termmale neonates. Using linear regression, we estimated geometric mean relative telomere length and tested for differences by race. Results. Black mothers were younger and had higher parity and black neonates had lower birth and placental weights. These factors were not associated with relative telomere length, even after adjusting for or stratifying by race. Relative telomere length in black (2.72) and white (2.73) neonates did not differ, even after adjusting for maternal or neonate factors (all p > 0.9). Conclusions. Maternal and neonate factors were not associated with cord blood telomere length, and telomere length did not differ by race. These findings suggest that telomere length at birth does not explain the prostate cancer racial disparity. C1 [Weber, Kari A.; Gonzalez, Beverly; Platz, Elizabeth A.] Johns Hopkins Bloomberg Sch Publ Hlth, Dept Epidemiol, 615 N Wolfe St, Baltimore, MD 21205 USA. [Heaphy, Christopher M.; Meeker, Alan K.] Johns Hopkins Univ, Dept Pathol, Sch Med, 600 N Wolfe St, Baltimore, MD 21287 USA. [Heaphy, Christopher M.; Platz, Elizabeth A.; Meeker, Alan K.] Sidney Kimmel Comprehens Canc Ctr Johns Hopkins, 401 N Broadway, Baltimore, MD 21287 USA. [Rohrmann, Sabine] Univ Zurich, Inst Social & Prevent Med, Dept Canc Epidemiol & Prevent, Hirschengraben 84, CH-8001 Zurich, Switzerland. [Bienstock, Jessica L.] Johns Hopkins Univ, Dept Gynecol & Obstet, Sch Med, 600 N Wolfe St, Baltimore, MD 21287 USA. [Agurs-Collins, Tanya] NCI, Div Canc Control & Populat Sci, 9609 Med Ctr Dr, Bethesda, MD 20892 USA. [Platz, Elizabeth A.; Meeker, Alan K.] Johns Hopkins Univ, Sch Med, Dept Urol, 600 N Wolfe St, Baltimore, MD 21287 USA. [Platz, Elizabeth A.; Meeker, Alan K.] Johns Hopkins Univ, Sch Med, James Buchanan Brady Urol Inst, 600 N Wolfe St, Baltimore, MD 21287 USA. RP Meeker, AK (reprint author), Johns Hopkins Univ, Dept Pathol, Sch Med, 600 N Wolfe St, Baltimore, MD 21287 USA.; Meeker, AK (reprint author), Sidney Kimmel Comprehens Canc Ctr Johns Hopkins, 401 N Broadway, Baltimore, MD 21287 USA.; Meeker, AK (reprint author), Johns Hopkins Univ, Sch Med, Dept Urol, 600 N Wolfe St, Baltimore, MD 21287 USA.; Meeker, AK (reprint author), Johns Hopkins Univ, Sch Med, James Buchanan Brady Urol Inst, 600 N Wolfe St, Baltimore, MD 21287 USA. EM alan.meeker@gmail.com OI Meeker, Alan/0000-0003-4601-6481 FU Department of Defense [W81XWH-06-1-0052]; National Cancer Institute Comprehensive Minority Institution/Cancer Center [Hopkins U54 CA091409, Howard U54 CA091431]; National Cancer Institute Cancer Center [P30 CA006973]; National Cancer Institute Institutional National Cancer Research Service Award [T32 CA0093140] FX The authors thank Stacey Cayetano, laboratory manager, at the Johns Hopkins Bloomberg School of Public Health, for her assistance in the conduct of this study. This work was supported by a Department of Defense Prostate Cancer Research Program grant (W81XWH-06-1-0052), a National Cancer Institute Comprehensive Minority Institution/Cancer Center Partnership grant (Hopkins U54 CA091409; Howard U54 CA091431), and a National Cancer Institute Cancer Center Support grant (P30 CA006973). Vitamin D measurements were supported by ISFE (Internationale Stiftung zur Foerderung der Ernaehrungsforschung und Ernaehrungsaufklaerung). Dr. Weber was supported by a National Cancer Institute Institutional National Cancer Research Service Award (T32 CA0093140). NR 49 TC 0 Z9 0 U1 0 U2 0 PU HINDAWI PUBLISHING CORP PI NEW YORK PA 315 MADISON AVE 3RD FLR, STE 3070, NEW YORK, NY 10017 USA SN 2090-3111 EI 2090-312X J9 PROSTATE CANCER JI Prostate Cancer PY 2016 AR 3691650 DI 10.1155/2016/3691650 PG 8 WC Oncology SC Oncology GA EF9WE UT WOS:000390680900001 ER PT J AU Yamaoka, S Ebihara, H AF Yamaoka, Satoko Ebihara, Hideki TI The two faces of Rift Valley fever virus virulence factor NSs: The development of a vaccine and the elucidation of pathogenesis SO VIRULENCE LA English DT Editorial Material DE differentiate infected from vaccinated animals (DIVA); interferon antagonism; live-attenuated vaccine; nonstructural protein NSs; Rift Valley fever ID DEPENDENT PROTEIN-KINASE; MP-12 VACCINE; SHEEP; LACKING; TRANSCRIPTION; BUNYAVIRIDAE; PHLEBOVIRUS; CHALLENGE; EFFICACY; IMMUNITY C1 [Yamaoka, Satoko; Ebihara, Hideki] NIAID, Mol Virol & Host Pathogen Interact Unit, Virol Lab, Div Intramural Res,NIH, Hamilton, MT USA. [Ebihara, Hideki] Mayo Clin, Dept Mol Med, Rochester, MN USA. RP Ebihara, H (reprint author), Mayo Clin, Guggenheim 18,200 First St SW, Rochester, MN 55905 USA. EM Ebihara.Hideki@mayo.edu NR 30 TC 0 Z9 0 U1 1 U2 1 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 530 WALNUT STREET, STE 850, PHILADELPHIA, PA 19106 USA SN 2150-5594 EI 2150-5608 J9 VIRULENCE JI Virulence PY 2016 VL 7 IS 8 BP 856 EP 859 DI 10.1080/21505594.2016.1213938 PG 4 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA EF6HK UT WOS:000390431500002 PM 27432532 ER PT J AU Plentz, RR Bitzer, M Greten, T Nadalin, S Vogel, A AF Plentz, Ruben R. Bitzer, Michael Greten, Tim Nadalin, Silvio Vogel, Arndt TI Future Therapy of Cholangiocarcinoma SO VISCERAL MEDICINE LA English DT Editorial Material C1 [Plentz, Ruben R.; Bitzer, Michael] Univ Hosp Tubingen, Dept Internal Med 1, Otfried Muller Str 10, D-72076 Tubingen, Germany. [Greten, Tim] NCI, Ctr Canc Res, Bldg 10,Room 3B43, Bethesda, MD 20892 USA. [Nadalin, Silvio] Univ Hosp Tubingen, Dept Visceral & Transplantat Surg, Hoppe Seyler Str 3, D-72076 Tubingen, Germany. [Vogel, Arndt] Hannover Med Sch, Dept Gastroenterol Hepatol & Endocrinol, Carl Neuberg Str 1, D-30625 Hannover, Germany. RP Plentz, RR (reprint author), Univ Hosp Tubingen, Dept Internal Med 1, Otfried Muller Str 10, D-72076 Tubingen, Germany. EM Ruben.Plentz@med.uni-tuebingen.de; Michael.Bitzer@med.uni-tuebingen.de; gretentf@mail.nih.gov; Silvio.Nadalin@med.uni-tuebingen.de; Vogel.Arndt@mh-hannover.de RI Vogel, Arndt/A-8437-2012 NR 2 TC 0 Z9 0 U1 0 U2 0 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 2297-4725 EI 2297-475X J9 VISC MED JI Visc. Med. PY 2016 VL 32 IS 6 BP 431 EP 433 DI 10.1159/000450720 PG 3 WC Surgery SC Surgery GA EF9YF UT WOS:000390686700008 PM 28229079 ER PT S AU Alambeigi, F Seifabadi, R Armand, M AF Alambeigi, Farshid Seifabadi, Reza Armand, Mehran BE Okamura, A Menciassi, A Ude, A Burschka, D Lee, D Arrichiello, F Liu, H Moon, H Neira, J Sycara, K Yokoi, K Martinet, P Oh, P Valdastri, P Krovi, V TI A Continuum Manipulator with Phase Changing Alloy SO 2016 IEEE INTERNATIONAL CONFERENCE ON ROBOTICS AND AUTOMATION (ICRA) SE IEEE International Conference on Robotics and Automation ICRA LA English DT Proceedings Paper CT IEEE International Conference on Robotics and Automation (ICRA) CY MAY 16-21, 2016 CL Royal Inst Technol, Ctr Autonomous Syst, Stockholm, SWEDEN SP IEEE, IEEE Robot & Automat Soc, ABB, DJI, KUKA, Husqvarna, iRobot, Khalifa Univ, Kinova Univ, MOOG, PAL Robot, UBER, Amazon HO Royal Inst Technol, Ctr Autonomous Syst ID DESIGN; CAPABILITY; COMPOSITE; RIGIDITY AB A new type of cable-driven continuum manipulator (CM) is presented, in which the stiffness of the device along its body length can be controlled using the thermomechanical properties of a phase changing alloy. The liquid phase of the alloy is used for achieving high dexterity and the solid phase for high stiffness. Joule heating and water cooling is used for transitioning the phase changing alloy between stiff and compliant states. Single-segment and two-segment working prototypes of the CM are demonstrated. The mechanical and thermodynamic features of these prototypes are discussed and their physical performance is investigated. Advantages of the presented design with phase changing alloy include: significantly improved dexterity, high payload to weight ratio, controllable stiffness, energy efficiency, and a large lumen. C1 [Alambeigi, Farshid; Armand, Mehran] Johns Hopkins Univ, Dept Mech Engn, Baltimore, MD 21218 USA. [Alambeigi, Farshid; Armand, Mehran] Johns Hopkins Univ, Lab Computat Sensing & Robot, Baltimore, MD 21218 USA. [Armand, Mehran] Johns Hopkins Univ, Appl Phys Lab, Laurel, MD USA. [Seifabadi, Reza] US Natl Inst Hlth NIH, Radiol & Imaging Sci, Bethesda, MD USA. RP Alambeigi, F (reprint author), Johns Hopkins Univ, Dept Mech Engn, Baltimore, MD 21218 USA.; Alambeigi, F (reprint author), Johns Hopkins Univ, Lab Computat Sensing & Robot, Baltimore, MD 21218 USA. EM falambe1@jhu.edu; mehran.armand@jhuapl.edu; rezaseifabadi@gmail.com NR 20 TC 0 Z9 0 U1 2 U2 2 PU IEEE PI NEW YORK PA 345 E 47TH ST, NEW YORK, NY 10017 USA SN 1050-4729 BN 978-1-4673-8026-3 J9 IEEE INT CONF ROBOT PY 2016 BP 758 EP 764 PG 7 WC Automation & Control Systems; Robotics SC Automation & Control Systems; Robotics GA BG5KH UT WOS:000389516200095 ER PT J AU Novick, T Liu, Y Alvanzo, A Zonderman, AB Evans, MK Crews, DC AF Novick, Tessa Liu, Yang Alvanzo, Anika Zonderman, Alan B. Evans, Michele K. Crews, Deidra C. TI Lifetime Cocaine and Opiate Use and Chronic Kidney Disease SO AMERICAN JOURNAL OF NEPHROLOGY LA English DT Article DE Chronic kidney disease; Substance abuse; Epidemiology; Cocaine; Opiates ID MESANGIAL CELL-PROLIFERATION; STAGE RENAL-DISEASE; ILLICIT DRUG-USE; FUNCTION DECLINE; MATRIX SYNTHESIS; MORPHINE; HYPERTENSION; NEPHROPATHY; MACROPHAGES; AMYLOIDOSIS AB Background: More than 50% of American adolescents and adults report having used illicit drugs in their lifetime. We examined the association of lifetime opiate and cocaine use with reduced kidney function, albuminuria and rapid kidney function decline among urban-dwelling adults. Methods: Our prospective cohort included 2,286 Healthy Aging in Neighborhoods of Diversity across the Life Span study participants who were community-dwelling adults residing in Baltimore, MD. The predictive variables were lifetime opiate and cocaine use, defined as use of opiates or crack/cocaine >= 5 times. Outcomes included prevalent reduced estimated glomerular filtration rate (eGFR; <60 ml/min/1.73 m(2) by Chronic Kidney Disease (CKD)-Epidemiology Collaboration), albuminuria (albumin-to-creatinine ratio >30 mg/g, n = 1,652) and rapid kidney function decline (>3 ml/min/1.73 m(2) per year over a median of 4.7 years, n = 1,660). Results: Participants' mean age was 48 years, 15% reported opiate use, and 22% reported cocaine use. A total of 115 (5.0%) participants had reduced eGFR, 190 (11.5%) had albuminuria and 230 (13.8%) experienced rapid decline in kidney function. In adjusted logistic regression analyses, both substances were associated with greater odds of reduced eGFR (OR 2.71, 95% CI 1.50-4.89 for opiates; OR 1.40, 95% CI 0.87-2.24 for cocaine). Both substances were associated with greater odds of albuminuria (OR 1.20, 95% CI 0.83-1.73 for opiates; OR 1.80, 95% CI 1.29-2.51 for cocaine). Neither substance was associated with the rapid decline of kidney function. Conclusions: Lifetime opiate and cocaine use was associated with prevalent reduced eGFR and albuminuria, yet not with rapid kidney function decline. The use of opiate and cocaine may be an important risk factor for CKD in urban populations. (C) 2016 S. Karger AG, Basel C1 [Novick, Tessa; Liu, Yang; Alvanzo, Anika; Crews, Deidra C.] Johns Hopkins Univ, Sch Med, Dept Med, 4940 Eastern Ave,301 Bldg,Suite 3400, Baltimore, MD 21224 USA. [Zonderman, Alan B.; Evans, Michele K.; Crews, Deidra C.] NIA, NIH, Baltimore, MD 21224 USA. Johns Hopkins Med Inst, Welch Ctr Prevent Epidemiol & Clin Res, Baltimore, MD 21205 USA. RP Novick, T (reprint author), Johns Hopkins Univ, Sch Med, Dept Med, 4940 Eastern Ave,301 Bldg,Suite 3400, Baltimore, MD 21224 USA. EM tnovick1@jhmi.edu OI Zonderman, Alan B/0000-0002-6523-4778 FU Intramural Research Program of the National Institute on Aging, National Institutes of Health (NIH); National Institute of Diabetes and Digestive and Kidney Diseases, NIH [K23DK097184] FX This work was supported by the Intramural Research Program of the National Institute on Aging, National Institutes of Health (NIH). Dr. Deidra C. Crews was supported by grant K23DK097184 from the National Institute of Diabetes and Digestive and Kidney Diseases, NIH. NR 36 TC 1 Z9 1 U1 2 U2 2 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 0250-8095 EI 1421-9670 J9 AM J NEPHROL JI Am. J. Nephrol. PY 2016 VL 44 IS 6 BP 447 EP 453 DI 10.1159/000452348 PG 7 WC Urology & Nephrology SC Urology & Nephrology GA EF1KA UT WOS:000390082500006 PM 27788520 ER PT J AU Dong, KZ Song, YZ Li, XD Ding, J Gao, ZY Lu, DP Zhu, YM AF Dong, Kezhou Song, Yanzhi Li, Xiaodong Ding, Jie Gao, Zhiyong Lu, Daopei Zhu, Yimin TI Pentasaccharides for the prevention of venous thromboembolism SO COCHRANE DATABASE OF SYSTEMATIC REVIEWS LA English DT Review ID DEEP-VEIN THROMBOSIS; MOLECULAR-WEIGHT HEPARIN; TOTAL HIP-REPLACEMENT; VITAMIN-K ANTAGONISTS; FACTOR XA INHIBITOR; BELOW-KNEE INJURY; POSTOPERATIVE FONDAPARINUX; ORTHOPEDIC-SURGERY; FRACTURE SURGERY; ELECTIVE HIP AB Background Venous thromboembolism (VTE) is a common condition with potentially serious and life-threatening consequences. The standard method of thromboprophylaxis uses an anticoagulant such as low molecular weight heparin (LMWH) or warfarin. In recent years, another type of anticoagulant, pentasaccharide, an indirect factor Xa inhibitor, has shown good anticoagulative effect in clinical trials. Three types of pentasaccharides are available: short-acting fondaparinux, long-acting idraparinux and idrabiotaparinux. Pentasaccharides cause little heparin-induced thrombocytopenia and are better tolerated than unfractionated heparin, LMWH and warfarin. However, no consensus has been reached on whether pentasaccharides are superior or inferior to other anticoagulative methods. Objectives To assess effects of pentasaccharides versus other methods of thromboembolic prevention (thromboprophylaxis) in people who require anticoagulant treatment to prevent venous thromboembolism. Search methods The Cochrane Vascular Information Specialist (CIS) searched the Specialised Register (last searched March 2016) and the Cochrane Central Register of ControlledTrials (CENTRAL; 2016, Issue 2). The CIS searched trial databases for details of ongoing and unpublished studies. Review authors searched LILACS (Latin American and Caribbean Health Sciences) and the reference lists of relevant studies and reviews identified by electronic searches. Selection criteria We included randomised controlled trials on any type of pentasaccharide versus other anticoagulation methods (pharmaceutical or mechanical) for VTE prevention. Data collection and analysis Two review authors independently selected trials, assessed methodological quality and extracted data in predesigned tables. Main results We included in this review 25 studies with a total of 21,004 participants. All investigated fondaparinux for VTE prevention; none investigated idraparinux or idrabiotaparinux. Studies included participants undergoing abdominal surgery, thoracic surgery, bariatric surgery or coronary bypass surgery; acutely ill hospitalised medical patients; people requiring rigid or semirigid immobilisation; and those with superficial venous thrombosis. Most studies focused on orthopaedic patients. We lowered the quality of the evidence because of heterogeneity between studies and a small number of events causing imprecision. When comparing fondaparinux with placebo, we found less total VTE (risk ratio (RR) 0.24, 95% confidence interval (CI) 0.15 to 0.38; 5717 participants; 8 studies; I-2 = 64%; P < 0.00001), less symptomatic VTE (RR 0.15, 95% CI 0.06 to 0.36; 6503 participants; 8 studies; I-2 = 0%; P < 0.0001), less total DVT (RR 0.25, 95% CI 0.15 to 0.40; 5715 participants; 8 studies; I-2 = 67%; P < 0.00001), less proximal DVT (RR 0.12, 95% CI 0.04 to 0.39; 2746 participants; 7 studies; I-2 = 64%; P = 0.0004) and less total pulmonary embolism (PE) (RR 0.16, 95% CI 0.04 to 0.62; 6412 participants; 8 studies; I-2 = 0%; P = 0.008) in the fondaparinux group. The quality of the evidence was moderate for total VTE, total DVT and proximal DVT, and high for symptomatic VTE and total PE. When fondaparinux was compared with LMWH, analyses indicated that fondaparinux reduced total VTE and DVT (RR 0.55, 95% CI 0.42 to 0.73; 9339 participants; 11 studies; I-2 = 64%; P < 0.0001; and RR 0.54, 95% CI 0.40 to 0.71; 9356 participants; 10 studies; I-2 = 67%; P < 0.0001, respectively), and showed a trend toward reduced proximal DVT (RR 0.58, 95% CI 0.33 to 1.02; 8361 participants; 9 studies; I-2 = 53%; P = 0.06). Symptomatic VTE (RR 1.03, 95% CI 0.65 to 1.63; 12240 participants; 9 studies; I-2 = 35%; P = 0.90) and total PE (RR 1.24, 95% CI 0.65 to 2.34; 12350 participants; 10 studies; I-2 = 0%; P = 0.51) indicated no difference between fondaparinux and LMWH. The quality of the evidence was moderate for total VTE, symptomatic VTE, total DVT and total PE, and low for proximal DVT. We showed that fondaparinux increased major bleeding compared with both placebo and LWMH (RR 2.56, 95% CI 1.48 to 4.44; 6659 participants; 8 studies; I-2 = 0%; P = 0.0008; moderate-quality evidence; and RR 1.38, 95% CI 1.09 to 1.75; 12,501 participants; 11 studies; I-2 = 24%; P = 0.008; high-quality evidence, respectively). All-cause mortality was not different between fondaparinux and placebo or LMWH (RR 0.76, 95% CI 0.48 to 1.22; 6674 participants; 8 studies; I-2 = 14%; P = 0.26; moderate-quality evidence; and RR 0.88, 95% CI 0.63 to 1.22; 12,400 participants; 11 studies; I-2 = 0%; P = 0.44; moderate-quality evidence, respectively). One study compared fondaparinux with variable and fixed (1 mg per day) doses of warfarin after elective hip or knee replacement surgery and showed no difference in primary and secondary outcomes between fondaparinux and both variable and fixed doses of warfarin. The quality of the evidence was very low. One small study compared fondaparinux with edoxaban in patients with severe renal impairment undergoing lower-limb orthopaedic surgery and reported no thromboembolic events, major bleeding events or deaths in either group. The quality of the evidence was very low. One small study compared fondaparinux with mechanical thromboprophylaxis. Results showed no difference in total VTE and total DVT between fondaparinux and mechanical thromboprophylaxis. This study reported no cases pertaining to the other outcomes of this review. The quality of the evidence was low. There were insufficient studies to permit meaningful conclusions for subgroups of clinical conditions other than orthopaedic surgery. Authors' conclusions Moderate to high quality evidence shows that fondaparinux is effective for short-termprevention of VTE when compared with placebo. It can reduce total VTE, DVT, total PE and symptomatic VTE, and does not demonstrate a reduction in deaths compared with placebo. Low to moderate quality evidence shows that fondaparinux is more effective for short-term VTE prevention when compared with LMWH. It can reduce total VTE and total DVT and does not demonstrate a reduction in deaths when compared with LMWH. However, at the same time, moderate to high quality evidence shows that fondaparinux increases major bleeding when compared with placebo and LMWH. Therefore, when fondaparinux is chosen for the prevention of VTE, attention should be paid to the person's bleeding and thrombosis risks. Most data were derived from patients undergoing orthopaedic surgery. Therefore, the conclusion predominantly pertains to these patients. Data on fondaparinux for other clinical conditions are sparse. C1 [Dong, Kezhou; Zhu, Yimin] Nanjing Univ Chinese Med, Jiangsu Prov Hosp TCM 2, Dept Respirat, Nanjing, Jiangsu, Peoples R China. [Song, Yanzhi; Gao, Zhiyong; Lu, Daopei] Fudan Univ, Shanghai Daopei Hosp, Shanghai, Peoples R China. [Li, Xiaodong] Nanjing Med Univ, Dept Radiotherapy, BenQ Med Ctr, Nanjing, Jiangsu, Peoples R China. [Ding, Jie] NIA, Lab Epidemiol & Populat Sci, NIH, Bethesda, MD 20892 USA. RP Song, YZ (reprint author), Fudan Univ, Shanghai Daopei Hosp, Shanghai, Peoples R China. EM yandgics@126.com FU Chief Scientist Office, Scottish Government Health Directorates, The Scottish Government, UK; Chief Scientist Office FX External sources; Chief Scientist Office, Scottish Government Health Directorates, The Scottish Government, UK.; The Cochrane Vascular editorial base is supported by the Chief Scientist Office NR 121 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1469-493X EI 1361-6137 J9 COCHRANE DB SYST REV JI Cochrane Database Syst Rev. PY 2016 IS 10 AR CD005134 DI 10.1002/14651858.CD005134.pub3 PG 223 WC Medicine, General & Internal SC General & Internal Medicine GA EE4UC UT WOS:000389599800016 ER PT J AU Wang, LQ Xu, M Southall, N Zheng, W Wang, SS AF Wang, Liqin Xu, Miao Southall, Noel Zheng, Wei Wang, Shuishu TI A High-Throughput Assay for Developing Inhibitors of PhoP, a Virulence Factor of Mycobacterium tuberculosis SO COMBINATORIAL CHEMISTRY & HIGH THROUGHPUT SCREENING LA English DT Article DE High-throughput screening; PhoP inhibitors; tuberculosis; FRET; protein-DNA complex; TB drugs ID RESPONSE REGULATOR PHOP; STREPTOMYCIN RESISTANCE; PROTECTIVE IMMUNITY; ENERGY-TRANSFER; VACCINE; STRAIN; TARGET; DOMAIN; GENE; BCG AB Background: Tuberculosis (TB) kills over 1.5 million people per year despite the available anti-TB drugs. The long duration needed to treat TB by the current TB drugs, which target the essential cellular activities, inevitably leads to the emergence of drug-resistance. The emergence of drug-resistant TB prompts for an urgent need for new and more effective drugs. Objective: The response regulator PhoP, an essential virulence factor of Mycobacterium tuberculosis (MTB), is an attractive target for developing novel anti-TB drugs. This study aims to develop a robust high-throughput screening assay to identify PhoP inhibitors that disrupt the PhoP-DNA binding. Method: Guided by the crystal structure of the PhoP-DNA complex, we designed and developed an assay based on Foster resonance energy transfer (FRET) by labeling Cy3 on the DNA and Cy5 on PhoP. We screened compound libraries for inhibitors that dissociated the PhoP-DNA complex by detection of the FRET signal. Hits were confirmed for their direct binding to PhoP by thermal shift assays. Results: From a test screening of similar to 6,000 bioactive compounds and approved drugs, three active compounds were identified that directly bound to PhoP and inhibited the PhoP-DNA interactions. These three PhoP inhibitors can be further developed to improve potency and are useful to study the mechanism of inhibition. Conclusion: Our results demonstrated that this FRET-based PhoP-DNA binding assay is valid for additional compound library screening to identify new leads for developing novel TB drugs that target the virulence of MTB. C1 [Wang, Liqin; Wang, Shuishu] Uniformed Serv Univ Hlth Sci, Dept Biochem & Mol Biol, 4301 Jones Bridge Rd, Bethesda, MD 20814 USA. [Xu, Miao; Southall, Noel; Zheng, Wei] NIH, Natl Ctr Adv Translat Sci, Bldg 10, Bethesda, MD 20892 USA. RP Wang, SS (reprint author), Uniformed Serv Univ Hlth Sci, Dept Biochem & Mol Biol, 4301 Jones Bridge Rd, Bethesda, MD 20814 USA. EM shuishu.wang@usuhs.edu FU National Institutes of Health [R01GM079185]; Uniformed Services University of the Health Sciences [R071IR, R0713018]; Intramural Research Program of the National Center for Advancing Translational Sciences (NCATS), National Institutes of Health FX The authors declare that they have no conflict of interest. This work was supported by the National Institutes of Health grant R01GM079185 and the Uniformed Services University of the Health Sciences intramural grants R071IR and R0713018 to S.W., and by the Intramural Research Program of the National Center for Advancing Translational Sciences (NCATS), National Institutes of Health to W.Z. The opinions or assertions contained herein are the private ones of the authors and are not to be construed as official or reflecting the views of the Department of Defense, Uniformed Services University of the Health Sciences, or National Institute of Health. NR 56 TC 0 Z9 0 U1 0 U2 0 PU BENTHAM SCIENCE PUBL LTD PI SHARJAH PA EXECUTIVE STE Y-2, PO BOX 7917, SAIF ZONE, 1200 BR SHARJAH, U ARAB EMIRATES SN 1386-2073 EI 1875-5402 J9 COMB CHEM HIGH T SCR JI Comb. Chem. High Throughput Screen PY 2016 VL 19 IS 10 BP 855 EP 864 DI 10.2174/1386207319666161010163249 PG 10 WC Biochemical Research Methods; Chemistry, Applied; Pharmacology & Pharmacy SC Biochemistry & Molecular Biology; Chemistry; Pharmacology & Pharmacy GA EF4XA UT WOS:000390334100008 ER PT J AU Li, CL Miao, Y Wang, YW Feng, J Wang, YB AF Li, Cai-Li Miao, Yan Wang, Ying-Wei Feng, Jing Wang, Yu-Bao TI Muscularization of pulmonary artery and RhoA/ROCK levels in rats exposed to intermittent hypoxia SO INTERNATIONAL JOURNAL OF CLINICAL AND EXPERIMENTAL PATHOLOGY LA English DT Article DE Intermittent hypoxemia; pulmonary hypertension; muscularization; RhoA/ROCK ID MUSCLE-CELL DIFFERENTIATION; POSITIVE AIRWAY PRESSURE; OBSTRUCTIVE SLEEP-APNEA; RHO-KINASE; CARDIOVASCULAR-DISEASE; VASCULAR-DISEASES; ANIMAL-MODELS; HYPERTENSION; INHIBITION; GROWTH AB Objective: Intermittent hypoxia (IH), as the most important pathophysiologic characteristic of obstructive sleep apnea (OSA) and a recognized risk factor for cardiovascular disorders, may lead to proliferation of smooth muscle cells (SMCs) and then pulmonary arterial remodeling through the RhoA/ROCK signaling pathway. In this preliminary study, an IH animal model was developed, and the muscularization of small pulmonary arteries and RhoA/ROCK levels in these rats exposed to IH were studied. Methods: Model rats were exposed to IH [cycles of hypoxia (30 s of 5% O-2) and normoxia (90 s of 21% O-2)] or intermittent normoxia [cycles of normoxia (30 s of 21% O-2) and normoxia (90 s of 21% O-2)] for 4 weeks, 9 AM to 5 PM in every day. Immunohistochemistry of a-smooth muscle actin (alpha-SMA) and proliferating cell nuclear antigen (PCNA) were used to measure muscularization and status of cell proliferation in small pulmonary arteries. Real-time polymerase chain reaction (RT-PCR) and Western blot analyses were used to assess levels of RhoA and ROCK expression. Results: A significantly increased ratio of alpha-SMA positive muscularized vessels and higher proliferative rate were observed in IH group compared with Control group (P < 0.05). Levels of RhoA/ROCK mRNA and protein in IH group were significantly higher than those in Control group (P < 0.05). Conclusion: Our preliminary data implicated that IH may induce proliferation of SMCs and then pulmonary arterial remodeling through the RhoA/ROCK signaling pathway, which may involve the development of PH. C1 [Li, Cai-Li; Feng, Jing] Tianjin Med Univ, Gen Hosp, Dept Resp, Tianjin 300052, Peoples R China. [Miao, Yan] Tianjin Med Univ, Tianjin, Peoples R China. [Wang, Ying-Wei] First Cent Hosp, Blood Transfus Dept, Tianjin, Peoples R China. [Feng, Jing] NIEHS, Neuropharacol Sect, Lab Toxicol & Pharmacol, NIH, POB 12233, Res Triangle Pk, NC 27709 USA. [Wang, Yu-Bao] Tianjin Med Univ, Affiliated Hosp 2, Infect Dis Inst, Tianjin, Peoples R China. RP Feng, J (reprint author), Tianjin Med Univ, Gen Hosp, Dept Resp, Tianjin 300052, Peoples R China. EM zyyhxkfengjing@126.com FU National Natural Science Foundation of China [81570084, 81270144, 30800507]; Natural Science Foundation of Tianjin City [13JCYBJC22400, 13JC-YBJC40000]; Tianjin Municipal Science and Technology Commission [09ZCZDSF04500] FX We are grateful to the information and correction from Jau-Shyong HONG Ph.D. of Neuropharmacology Section, Laboratory of Toxicology & Pharmacology, National Institute of Environmental Health Sciences, National Institutes of Health, Research Triangle Park, NC 27709, USA. This study was supported by grants from the National Natural Science Foundation of China (81570084, 81270144, and 30800507); by grants from the Natural Science Foundation of Tianjin City (13JCYBJC22400 and 13JC-YBJC40000); and by grant from the Tianjin Municipal Science and Technology Commission (09ZCZDSF04500). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 45 TC 0 Z9 0 U1 2 U2 2 PU E-CENTURY PUBLISHING CORP PI MADISON PA 40 WHITE OAKS LN, MADISON, WI 53711 USA SN 1936-2625 J9 INT J CLIN EXP PATHO JI Int. J. Clin. Exp. Pathol. PY 2016 VL 9 IS 10 BP 10139 EP 10148 PG 10 WC Oncology; Pathology SC Oncology; Pathology GA EF5WJ UT WOS:000390400000042 ER PT J AU Saylor, KW AF Saylor, Katherine Witte TI Multiple approaches to understanding and preventing elder abuse: Introduction to the cross-disciplinary National Institutes of Health workshop SO JOURNAL OF ELDER ABUSE & NEGLECT LA English DT Editorial Material DE Child abuse; cross-disciplinary; elder abuse research; intimate partner violence; National Institutes of Health; workshop AB On October 30, 2015, the National Institutes of Health (NIH) convened a workshop, "Multiple Approaches to Understanding and Preventing Elder Abuse," in Bethesda, Maryland. The workshop brought together experts from across disciplines to discuss research challenges, opportunities, and lessons learned from other fields. Participants included experts in elder abuse, child abuse, intimate partner violence (IPV), emergency medicine, and neuroscience. In this special issue of the Journal of Elder Abuse and Neglect, participants address topics explored before, during, and after the day-long workshop. C1 [Saylor, Katherine Witte] NIH, Off Sci Policy, Bldg 10, Bethesda, MD 20892 USA. RP Saylor, KW (reprint author), Univ N Carolina, Dept Publ Policy, Abernethy Hall, Chapel Hill, NC 27599 USA. EM kwsaylor@live.unc.edu NR 1 TC 1 Z9 1 U1 1 U2 1 PU ROUTLEDGE JOURNALS, TAYLOR & FRANCIS LTD PI ABINGDON PA 2-4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXON, ENGLAND SN 0894-6566 EI 1540-4129 J9 J ELDER ABUSE NEGL JI J. Elder Abuse Negl. PY 2016 VL 28 IS 4-5 BP 179 EP 184 DI 10.1080/08946566.2016.1235998 PG 6 WC Gerontology SC Geriatrics & Gerontology GA EF3PD UT WOS:000390235700001 PM 27636385 ER PT J AU Jervis, LL Hamby, S Beach, SR Williams, ML Maholmes, V Castille, DM AF Jervis, Lori L. Hamby, Sherry Beach, Scott R. Williams, Mary L. Maholmes, Valerie Castille, Dorothy M. TI Elder mistreatment in underserved populations: Opportunities and challenges to developing a contemporary program of research SO JOURNAL OF ELDER ABUSE & NEGLECT LA English DT Article DE Elder mistreatment; ethnic/racial minorities; poverty; rural; underserved ID AFRICAN-AMERICANS; FINANCIAL EXPLOITATION; PARTICIPATORY RESEARCH; UNITED-STATES; OLDER-ADULTS; RISK-FACTORS; ABUSE; PREVALENCE; HEALTH; COMMUNITY AB This article provides an overview of the status of research on elder mistreatment among underserved populations in the United States, including gaps in our current knowledge base and scientific and structural barriers to growing research on the exploitation, neglect, and abuse of older people from diverse and disadvantaged ethnic/racial, geographic, sexual identity, and socioeconomic groups. High-priority areas in need of new elder mistreatment research with underserved populations are identified, and suggestions are given for how this research can be facilitated by researchers, university institutional review boards, and funding agencies. C1 [Jervis, Lori L.; Williams, Mary L.] Univ Oklahoma, Dept Anthropol, Norman, OK 73019 USA. [Jervis, Lori L.] Univ Oklahoma, Ctr Appl Social Res, 201 Stephenson Pkwy 4100, Norman, OK 73019 USA. [Hamby, Sherry] Life Paths Appalachian Res Ctr, Monteagle, TN USA. [Hamby, Sherry] Univ South, Dept Psychol, Sewanee, TN USA. [Beach, Scott R.] Univ Pittsburgh, UCSUR, Pittsburgh, PA USA. [Maholmes, Valerie] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Pediat Trauma & Crit Illness Branch, NIH, Bethesda, MD USA. [Castille, Dorothy M.] Natl Inst Minor Hlth & Hlth Dispar, NIH, Bethesda, MD USA. RP Jervis, LL (reprint author), Univ Oklahoma, Ctr Appl Social Res, 201 Stephenson Pkwy 4100, Norman, OK 73019 USA. EM lori.jervis@ou.edu NR 95 TC 0 Z9 0 U1 0 U2 0 PU ROUTLEDGE JOURNALS, TAYLOR & FRANCIS LTD PI ABINGDON PA 2-4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXON, ENGLAND SN 0894-6566 EI 1540-4129 J9 J ELDER ABUSE NEGL JI J. Elder Abuse Negl. PY 2016 VL 28 IS 4-5 BP 301 EP 319 DI 10.1080/08946566.2016.1245644 PG 19 WC Gerontology SC Geriatrics & Gerontology GA EF3PD UT WOS:000390235700006 PM 27739929 ER PT J AU Sheridan, MJ AF Sheridan, Michael J. TI Social Justice Counseling: The Next Steps Beyond Multiculturalism SO JOURNAL OF RELIGION AND SPIRITUALITY IN SOCIAL WORK LA English DT Book Review C1 [Sheridan, Michael J.] NIH, Divers & Wellness Programs, Bldg 10, Bethesda, MD 20892 USA. RP Sheridan, MJ (reprint author), NIH, Divers & Wellness Programs, Bldg 10, Bethesda, MD 20892 USA. EM michael.sheridan@nih.gov NR 1 TC 0 Z9 0 U1 0 U2 0 PU ROUTLEDGE JOURNALS, TAYLOR & FRANCIS LTD PI ABINGDON PA 2-4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXON, ENGLAND SN 1542-6432 EI 1542-6440 J9 J RELIG SPIRITUAL SO JI J. Relig. Spiritual. Soc. Work PY 2016 VL 35 IS 4 BP 412 EP 413 DI 10.1080/15426432.2016.1220691 PG 2 WC Social Work SC Social Work GA EF2ZN UT WOS:000390194200009 ER PT J AU Cousin, SF Charlier, C Kaderavek, P Marquardsen, T Tyburn, JM Bovier, PA Ulzega, S Speck, T Wilhelm, D Engelke, F Maas, W Sakellariou, D Bodenhausen, G Pelupessy, P Ferrage, F AF Cousin, Samuel F. Charlier, Cyril Kaderavek, Pavel Marquardsen, Thorsten Tyburn, Jean-Max Bovier, Pierre-Alain Ulzega, Simone Speck, Thomas Wilhelm, Dirk Engelke, Frank Maas, Werner Sakellariou, Dimitrios Bodenhausen, Geoffrey Pelupessy, Philippe Ferrage, Fabien TI High-resolution two-field nuclear magnetic resonance spectroscopy SO PHYSICAL CHEMISTRY CHEMICAL PHYSICS LA English DT Article ID FIELD-CYCLING DEVICE; NMR-SPECTROSCOPY; BIOMOLECULAR NMR; CONTRAST AGENTS; STATE NMR; DYNAMICS; PROTEIN; RELAXOMETRY; RELAXATION; DESIGN AB Nuclear magnetic resonance (NMR) is a ubiquitous branch of spectroscopy that can explore matter at the scale of an atom. Significant improvements in sensitivity and resolution have been driven by a steady increase of static magnetic field strengths. However, some properties of nuclei may be more favourable at low magnetic fields. For example, transverse relaxation due to chemical shift anisotropy increases sharply at higher magnetic fields leading to line-broadening and inefficient coherence transfers. Here, we present a two-field NMR spectrometer that permits the application of rf-pulses and acquisition of NMR signals in two magnetic centres. Our prototype operates at 14.1 T and 0.33 T. The main features of this system are demonstrated by novel NMR experiments, in particular a proof-of-concept correlation between zero-quantum coherences at low magnetic field and single quantum coherences at high magnetic field, so that high resolution can be achieved in both dimensions, despite a ca. 10 ppm inhomogeneity of the low-field centre. Two-field NMR spectroscopy offers the possibility to circumvent the limits of high magnetic fields, while benefiting from their exceptional sensitivity and resolution. This approach opens new avenues for NMR above 1 GHz. C1 [Cousin, Samuel F.; Charlier, Cyril; Kaderavek, Pavel; Bodenhausen, Geoffrey; Pelupessy, Philippe; Ferrage, Fabien] UPMC Univ Paris 06, PSL Res Univ, Ecole Normale Super, Dept Chim,CNRS,Lab Biomol LBM, 24 Rue Lhomond, F-75005 Paris, France. [Cousin, Samuel F.; Charlier, Cyril; Kaderavek, Pavel; Bodenhausen, Geoffrey; Pelupessy, Philippe; Ferrage, Fabien] UPMC Univ Paris 06, Sorbonne Univ, Ecole Normale Super, CNRS,Lab Biomol LBM, Paris, France. [Marquardsen, Thorsten; Engelke, Frank] Bruker BioSpin GmbH, Silberstreifen 4, D-76287 Rheinstetten, Germany. [Tyburn, Jean-Max] Bruker BioSpin, 34 Rue Ind BP 10002, F-67166 Wissembourg, France. [Bovier, Pierre-Alain; Ulzega, Simone; Speck, Thomas; Wilhelm, Dirk] Bruker BioSpin AG, Ind Str 26, CH-8117 Fallanden, Switzerland. [Maas, Werner] Bruker BioSpin, Billerica, MA 01821 USA. [Sakellariou, Dimitrios] Univ Paris Saclay, CEA Saclay, CEA CNRS, NIMBE, F-91191 Gif Sur Yvette, France. [Charlier, Cyril] NIDDK, Chem Phys Lab, NIH, Bethesda, MD 20892 USA. [Ulzega, Simone] Swiss Fed Inst Aquat Sci & Technol, Eawag, CH-8600 Dubendorf, Switzerland. [Wilhelm, Dirk] Zurich Univ Appl Sci, ZHAW, Inst Appl Math & Phys, Technikumstr 9, CH-8400 Winterthur, Switzerland. RP Ferrage, F (reprint author), UPMC Univ Paris 06, PSL Res Univ, Ecole Normale Super, Dept Chim,CNRS,Lab Biomol LBM, 24 Rue Lhomond, F-75005 Paris, France.; Ferrage, F (reprint author), UPMC Univ Paris 06, Sorbonne Univ, Ecole Normale Super, CNRS,Lab Biomol LBM, Paris, France. EM Fabien.Ferrage@ens.fr FU European Research Council (ERC) under the European Community Seventh Framework Program (FP7), ERC [279519 (2F4BIODYN)]; Agence Nationale de la Recherche [ANR-11-BS07-031-01] FX This work was funded by the European Research Council (ERC) under the European Community Seventh Framework Program (FP7/2007-2013), ERC Grant Agreement 279519 (2F4BIODYN), as well as the Agence Nationale de la Recherche (ANR-11-BS07-031-01). NR 57 TC 0 Z9 0 U1 12 U2 12 PU ROYAL SOC CHEMISTRY PI CAMBRIDGE PA THOMAS GRAHAM HOUSE, SCIENCE PARK, MILTON RD, CAMBRIDGE CB4 0WF, CAMBS, ENGLAND SN 1463-9076 EI 1463-9084 J9 PHYS CHEM CHEM PHYS JI Phys. Chem. Chem. Phys. PY 2016 VL 18 IS 48 BP 33187 EP 33194 DI 10.1039/c6cp05422f PG 8 WC Chemistry, Physical; Physics, Atomic, Molecular & Chemical SC Chemistry; Physics GA EF6IY UT WOS:000390435800063 PM 27892567 ER PT J AU Evans, SR Follmann, D AF Evans, Scott R. Follmann, Dean TI Using Outcomes to Analyze Patients Rather than Patients to Analyze Outcomes: A Step Toward Pragmatism in Benefit:Risk Evaluation SO STATISTICS IN BIOPHARMACEUTICAL RESEARCH LA English DT Article DE Benefit:risk; Clinical trials; DOOR; Partial credit strategy; Pragmatism ID COMPOSITE END-POINTS; CLINICAL-TRIALS; RISK ANALYSIS; COLISTIN; INNOVATION; SELECTION; FAILURE; DISEASE; ISSUES AB In the future, clinical trials will have an increased emphasis on pragmatism, providing a practical description of the effects of new treatments in realistic clinical settings. Accomplishing pragmatism requires better summaries of the totality of the evidence in ways that clinical trials consumerspatients, physicians, insurersfind transparent and allow for informed benefit:risk decision-making.The current approach to the analysis of clinical trials is to analyze efficacy and safety separately and then combine these analyses into a benefit:risk assessment. Many assume that this will effectively describe the impact on patients. But this approach is suboptimal for evaluating the totality of effects on patients.We discuss methods for benefit:risk assessment that have greater pragmatism than methods that separately analyze efficacy and safety. These include the concepts of within-patient analyses and composite benefit:risk endpoints with a goal of understanding how to analyze one patient before trying to figure out how to analyze many. We discuss the desirability of outcome ranking (DOOR) and introduce the partial credit strategy using an example in a clinical trial evaluating the effects of a new antibiotic. As part of the example, we introduce a strategy to engage patients as a resource to inform benefit:risk analyses consistent with the goal of measuring and weighing outcomes that are most important from the patient's perspective.We describe a broad vision for the future of clinical trials consistent with increased pragmatism. Greater focus on using endpoints to analyze patients rather than patients to analyze endpoints particularly in late-phase/stage clinical trials is an important part of this vision. C1 [Evans, Scott R.] Harvard Univ, Dept Biostat, Boston, MA 02115 USA. [Evans, Scott R.] Harvard Univ, Ctr Biostat AIDS Res, Boston, MA 02115 USA. [Follmann, Dean] NIAID, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA. RP Evans, SR (reprint author), Harvard Univ, Dept Biostat, Boston, MA 02115 USA. EM evans@sdac.harvard.edu FU National Institute of Allergy and Infectious Diseases of the NIH [UM1AI104681] FX This work was supported by the National Institute of Allergy and Infectious Diseases of the NIH (award number UM1AI104681). NR 30 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 1946-6315 J9 STAT BIOPHARM RES JI Stat. Biopharm. Res. PY 2016 VL 8 IS 4 BP 386 EP 393 DI 10.1080/19466315.2016.1207561 PG 8 WC Mathematical & Computational Biology; Statistics & Probability SC Mathematical & Computational Biology; Mathematics GA EF5XN UT WOS:000390403300005 ER PT S AU Xue, ZY Rahman, MM Antani, S Long, LR Denmer-Fushman, D Thoma, GR AF Xue, Zhiyun Rahman, Md Mahmudur Antani, Sameer Long, L. Rodney Denmer-Fushman, Dina Thoma, George R. GP IEEE TI Modality Classification for Searching Figures in Biomedical Literature SO 2016 IEEE 29TH INTERNATIONAL SYMPOSIUM ON COMPUTER-BASED MEDICAL SYSTEMS (CBMS) SE IEEE International Symposium on Computer-Based Medical Systems LA English DT Proceedings Paper CT 29th IEEE International Symposium on Computer-Based Medical Systems (CBMS) CY JUN 20-23, 2016 CL NORTH IRELAND SP IEEE, IEEE Comp Soc, IEEE Comp Soc Tech Comm Computat Life Sci, Queens Univ, Karlstads Univ, Royal Acad Med Ireland, Univ Dublin, Trinity Coll Dublin, No Ireland Connected Hlth Innovat Ctr, Failte Ireland, Assoc Comp Machinery, IEEE Life Sci DE Modality classification; figure searching; concept feature; support vector machine; deep learning; convolutional neural networks ID RETRIEVAL AB Image modality classification categorizes images according to their type. It is an important module in the Open-i(SM) multimodal (text+image) search engine that retrieves figures from biomedical articles. It is a hierarchical classification where on the top level the input figures are classified into two general categories: regular images (X-ray, CT, MRI, photographs, etc.) vs. illustration images (cartoon sketch, charts, graphs, etc.). This binary classification task is challenged by the vast diversity of visual material (image type), and the way it is organized (simple or compound figures). We present two methods for this binary classification: (i) Support Vector Machines (SVM) with manually-selected features, including a feature based on semantic concepts; and, (ii) Deep Learning method which avoids the process of feature handcrafting. Both methods were tested and compared on a dataset of 16400 figures. Both methods achieved good performance (above 95% accuracy). The slightly better performance of the feature-based method demonstrates the effectiveness of the features we chose. C1 [Xue, Zhiyun; Antani, Sameer; Long, L. Rodney; Denmer-Fushman, Dina; Thoma, George R.] Natl Lib Med, Lister Hill Natl Ctr Biomed Commun, Bethesda, MD 20894 USA. [Rahman, Md Mahmudur] Morgan State Univ, Dept Comp Sci, Baltimore, MD 21239 USA. RP Xue, ZY (reprint author), Natl Lib Med, Lister Hill Natl Ctr Biomed Commun, Bethesda, MD 20894 USA. EM xuez@mail.nih.gov; md.rahman@morgan.edu; santani@mail.nih.gov; rlong@mail.nih.gov; ddemner@mail.nih.gov; gthoma@mail.nih.gov NR 16 TC 0 Z9 0 U1 0 U2 0 PU IEEE PI NEW YORK PA 345 E 47TH ST, NEW YORK, NY 10017 USA SN 2372-9198 BN 978-1-4673-9036-1 J9 COMP MED SY PY 2016 BP 152 EP 157 DI 10.1109/CBMS.2016.29 PG 6 WC Computer Science, Information Systems; Computer Science, Interdisciplinary Applications; Engineering, Biomedical SC Computer Science; Engineering GA BG5OP UT WOS:000389611300029 ER PT S AU Kim, J Thoma, GR LoBuglio, P AF Kim, Jongwoo Thoma, George R. LoBuglio, Paul GP IEEE TI Visualization of Statistics from MEDLINE (R) SO 2016 IEEE 29TH INTERNATIONAL SYMPOSIUM ON COMPUTER-BASED MEDICAL SYSTEMS (CBMS) SE IEEE International Symposium on Computer-Based Medical Systems LA English DT Proceedings Paper CT 29th IEEE International Symposium on Computer-Based Medical Systems (CBMS) CY JUN 20-23, 2016 CL NORTH IRELAND SP IEEE, IEEE Comp Soc, IEEE Comp Soc Tech Comm Computat Life Sci, Queens Univ, Karlstads Univ, Royal Acad Med Ireland, Univ Dublin, Trinity Coll Dublin, No Ireland Connected Hlth Innovat Ctr, Failte Ireland, Assoc Comp Machinery, IEEE Life Sci DE MEDLINE; statistics; affiliation; visualization AB We propose a system to visualize statistics collected from NLM's MEDLINE (R) database that contains citations related to biomedical journal articles. The system extracts information from author affiliations in the articles such as organization, city, state, country, etc., categorizes the articles into several groups using the information, collects statistics such as the number of articles published per country each year, etc., and displays the statistics through a Web site using tables and choropleth maps. Hidden Markov Model (HMM) and statistics are used to extract the information from the affiliations, and Google Map API, JSON, JavaScript and other APIs are used for the development of the site. C1 [Kim, Jongwoo; Thoma, George R.] Natl Lib Med, Lister Hill Natl Ctr Biomed Commun, Bethesda, MD 20894 USA. [LoBuglio, Paul] Univ Toronto, Dept Comp Sci, Toronto, ON, Canada. RP Kim, J (reprint author), Natl Lib Med, Lister Hill Natl Ctr Biomed Commun, Bethesda, MD 20894 USA. EM jongkim@mail.nih.gov NR 2 TC 0 Z9 0 U1 0 U2 0 PU IEEE PI NEW YORK PA 345 E 47TH ST, NEW YORK, NY 10017 USA SN 2372-9198 BN 978-1-4673-9036-1 J9 COMP MED SY PY 2016 BP 290 EP 291 DI 10.1109/CBMS.2016.61 PG 2 WC Computer Science, Information Systems; Computer Science, Interdisciplinary Applications; Engineering, Biomedical SC Computer Science; Engineering GA BG5OP UT WOS:000389611300058 ER PT S AU Raben, N Puertollano, R AF Raben, Nina Puertollano, Rosa BE Schekman, R TI TFEB and TFE3: Linking Lysosomes to Cellular Adaptation to Stress SO ANNUAL REVIEW OF CELL AND DEVELOPMENTAL BIOLOGY, VOL 32 SE Annual Review of Cell and Developmental Biology LA English DT Review; Book Chapter DE autophagy; lysosomes; mTOR; TFE3; TFEB; stress ID TRANSCRIPTION FACTOR EB; HOGG-DUBE-SYNDROME; AMYLOID PLAQUE PATHOGENESIS; AMINO-ACID LEVELS; TRANSGENIC MICE; ALPHA-SYNUCLEIN; RAG GTPASES; REGULATES AUTOPHAGY; PARKINSONS-DISEASE; MOUSE MODEL AB In recent years, our vision of lysosomes has drastically changed. Formerly considered to be mere degradative compartments, they are now recognized as key players in many cellular processes. The ability of lysosomes to respond to different stimuli revealed a complex and coordinated regulation of lysosomal gene expression. This review discusses the participation of the transcription factors TFEB and TFE3 in the regulation of lysosomal function and biogenesis, as well as the role of the lysosomal pathway in cellular adaptation to a variety of stress conditions, including nutrient deprivation, mitochondrial dysfunction, protein misfolding, and pathogen infection. We also describe how cancer cells make use of TFEB and TFE3 to promote their own survival and highlight the potential of these transcription factors as therapeutic targets for the treatment of neurological and lysosomal diseases. C1 [Raben, Nina] NIAMSD, Lab Muscle Stem Cells & Gene Regulat, NIH, Bethesda, MD 20892 USA. [Puertollano, Rosa] NHLBI, Cell Biol & Physiol Ctr, NIH, Bldg 10, Bethesda, MD 20892 USA. RP Raben, N (reprint author), NIAMSD, Lab Muscle Stem Cells & Gene Regulat, NIH, Bethesda, MD 20892 USA. EM rabenn@mail.nih.gov; puertolr@mail.nih.gov NR 138 TC 2 Z9 2 U1 11 U2 11 PU ANNUAL REVIEWS PI PALO ALTO PA 4139 EL CAMINO WAY, PO BOX 10139, PALO ALTO, CA 94303-0897 USA SN 1081-0706 BN 978-0-8243-3132-0 J9 ANNU REV CELL DEV BI JI Annu. Rev. Cell Dev.Biol. PY 2016 VL 32 BP 255 EP 278 DI 10.1146/annurev-cellbio-111315-125407 PG 24 WC Cell Biology; Developmental Biology SC Cell Biology; Developmental Biology GA BG5NA UT WOS:000389576900010 PM 27298091 ER PT S AU Molina-Cruz, A Zilversmit, MM Neafsey, DE Hartl, DL Barillas-Mury, C AF Molina-Cruz, Alvaro Zilversmit, Martine M. Neafsey, Daniel E. Hartl, Daniel L. Barillas-Mury, Carolina BE Bonini, NM TI Mosquito Vectors and the Globalization of Plasmodium falciparum Malaria SO ANNUAL REVIEW OF GENETICS, VOL 50 SE Annual Review of Genetics LA English DT Review; Book Chapter DE malaria globalization; Plasmodium falciparum; Anopheles mosquito; antiplasmodial immunity; immune evasion ID ANOPHELES-GAMBIAE; MIDGUT CELLS; RECENT ORIGIN; POPULATION-STRUCTURE; OOKINETE INVASION; NATURAL-SELECTION; SURFACE PROTEIN; SOUTH-AMERICA; CYTOCHROME-B; VAR GENES AB Plasmodium falciparum malaria remains a devastating public health problem. Recent discoveries have shed light on the origin and evolution of Plasmodium parasites and their interactions with their vertebrate and mosquito hosts. P. falciparum malaria originated in Africa from a single horizontal transfer between an infected gorilla and a human, and became global as the result of human migration. Today, P. falciparum malaria is transmitted worldwide by more than 70 different anopheline mosquito species. Recent studies indicate that the mosquito immune system can be a barrier to malaria transmission and that the P. falciparum Pfs47 gene allows the parasite to evade mosquito immune detection. Here, we review the origin and globalization of P. falciparum and integrate this history with analysis of the biology, evolution, and dispersal of the main mosquito vectors. This new perspective broadens our understanding of P. falciparum population structure and the dispersal of important parasite genetic traits. C1 [Molina-Cruz, Alvaro; Barillas-Mury, Carolina] NIAID, Lab Malaria & Vector Res, NIH, Rockville, MD 20852 USA. [Zilversmit, Martine M.] Amer Museum Nat Hist, Richard Guilder Grad Sch, New York, NY 10024 USA. [Zilversmit, Martine M.] Amer Museum Nat Hist, Sackler Inst Comparat Genom, New York, NY 10024 USA. [Neafsey, Daniel E.] Broad Inst MIT & Harvard, Genome Sequencing & Anal Program, Cambridge, MA 02142 USA. [Hartl, Daniel L.] Harvard Univ, Dept Organism & Evolutionary Biol, Cambridge, MA 02138 USA. RP Barillas-Mury, C (reprint author), NIAID, Lab Malaria & Vector Res, NIH, Rockville, MD 20852 USA. EM cbarillas@niaid.nih.gov FU NIAID NIH HHS [R01 AI099105, R01 AI106734] NR 111 TC 3 Z9 3 U1 3 U2 3 PU ANNUAL REVIEWS PI PALO ALTO PA 4139 EL CAMINO WAY, PO BOX 10139, PALO ALTO, CA 94303-0897 USA SN 0066-4197 BN 978-0-8243-1250-3 J9 ANNU REV GENET JI Annu. Rev. Genet. PY 2016 VL 50 BP 447 EP 465 DI 10.1146/annurev-genet-120215-035211 PG 19 WC Genetics & Heredity SC Genetics & Heredity GA BG5NP UT WOS:000389584800020 PM 27732796 ER PT S AU Lakdawala, SS Fodor, E Subbarao, K AF Lakdawala, Seema S. Fodor, Ervin Subbarao, Kanta BE Enquist, LW TI Moving On Out: Transport and Packaging of Influenza Viral RNA into Virions SO ANNUAL REVIEW OF VIROLOGY, VOL 3 SE Annual Review of Virology LA English DT Review; Book Chapter DE influenza; nuclear export; cytoplasmic transport; packaging; assembly; viral RNA ID EFFICIENT VIRUS-REPLICATION; PROTEIN CYTOPLASMIC TAIL; A VIRUS; NUCLEAR EXPORT; RIBONUCLEOPROTEIN COMPLEXES; M1 PROTEIN; ACTIN CYTOSKELETON; GENE SEGMENTS; GENOME; POLYMERASE AB Influenza A viruses bear an eight-segmented single-stranded negative-sense RNA genome that is replicated in the nucleus. Newly synthesized viral RNA (vRNA) segments are exported from the nucleus and transported to the plasma membrane for packaging into progeny virions. Influenza viruses exploit many host proteins during these events, and this is the portion of the viral life cycle when genetic reassortment among influenza viruses occurs. Reassortment among influenza A viruses allows viruses to expand their host range, virulence, and pandemic potential. This review covers recent studies on the export of vRNAs from the nucleus and their transport through the cytoplasm, progressive assembly, and packaging into progeny virus particles. Understanding these events and the constraints on genetic reassortment has implications for assessment of the pandemic potential of newly emerged influenza viruses, for vaccine production, for determination of viral fitness, and for identification of novel therapeutic targets. C1 [Lakdawala, Seema S.] Univ Pittsburgh, Sch Med, Dept Microbiol & Mol Genet, Pittsburgh, PA 15219 USA. [Fodor, Ervin] Univ Oxford, Sir William Dunn Sch Pathol, Oxford OX1 3RE, England. [Subbarao, Kanta] NIAID, Infect Dis Lab, NIH, Bethesda, MD 20892 USA. RP Subbarao, K (reprint author), NIAID, Infect Dis Lab, NIH, Bethesda, MD 20892 USA. EM ksubbarao@niaid.nih.gov NR 74 TC 0 Z9 0 U1 1 U2 1 PU ANNUAL REVIEWS PI PALO ALTO PA 4139 EL CAMINO WAY, PO BOX 10139, PALO ALTO, CA 94303-0897 USA SN 2327-056X BN 978-0-8243-3403-1 J9 ANNU REV VIROL PY 2016 VL 3 BP 411 EP 427 DI 10.1146/annurev-virology-110615-042345 PG 17 WC Virology SC Virology GA BG5NR UT WOS:000389586100019 PM 27741407 ER PT J AU Hadigan, C Howard, L Sheehan, J Morse, CG Ahmed, C Thomas, A Silk, R Rosenthal, ES Kattakuzhy, S Kleiner, DE Kottilil, S AF Hadigan, C. Howard, L. Sheehan, J. Morse, C. G. Ahmed, C. Thomas, A. Silk, R. Rosenthal, E. S. Kattakuzhy, S. Kleiner, D. E. Kottilil, S. TI Persistent aminotransferase elevations following HCV clearance in adults with and without HIV SO ANTIVIRAL THERAPY LA English DT Meeting Abstract CT 18th International Workshop on Co-Morbidities and Adverse Drug Reactions in HIV CY SEP 12-13, 2016 CL New York, NY C1 [Hadigan, C.; Howard, L.; Sheehan, J.; Ahmed, C.; Thomas, A.; Kottilil, S.] NIAID, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA. [Morse, C. G.] NIH, CCMD, Bldg 10, Bethesda, MD 20892 USA. [Silk, R.; Rosenthal, E. S.; Kattakuzhy, S.; Kottilil, S.] Univ Maryland, Inst Human Virol, Baltimore, MD 21201 USA. [Kleiner, D. E.] NCI, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU INT MEDICAL PRESS LTD PI LONDON PA 2-4 IDOL LANE, LONDON EC3R 5DD, ENGLAND SN 1359-6535 J9 ANTIVIR THER JI Antivir. Ther. PY 2016 VL 21 SU 1 MA O24 BP A27 EP A27 PG 1 WC Infectious Diseases; Pharmacology & Pharmacy; Virology SC Infectious Diseases; Pharmacology & Pharmacy; Virology GA EE6UF UT WOS:000389747500025 ER PT J AU Jones, SE Mattingly, AS Unsal, AB Purdy, JB Kopp, JB Hazra, R Hadigan, C AF Jones, S. E. Mattingly, A. S. Unsal, A. B. Purdy, J. B. Kopp, J. B. Hazra, R. Hadigan, C. TI Evaluation of renal function in young adults who acquired HIV infection in early life SO ANTIVIRAL THERAPY LA English DT Meeting Abstract CT 18th International Workshop on Co-Morbidities and Adverse Drug Reactions in HIV CY SEP 12-13, 2016 CL New York, NY C1 [Jones, S. E.] Leidos Biomed Res Inc, Clin Monitoring Res Program, Clin Res Directorate, NCI Campus Frederick, Frederick, MD USA. [Mattingly, A. S.; Unsal, A. B.; Hadigan, C.] NIAID, Immunoregulat Lab, Bldg 10, Bethesda, MD 20892 USA. [Purdy, J. B.] NIH, Dept Crit Care Med, Ctr Clin, Bethesda, MD 20892 USA. [Kopp, J. B.] NIDDK, Kidney Dis Branch, Bethesda, MD 20892 USA. [Hazra, R.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Maternal & Pediat Infect Dis Branch, NIH, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU INT MEDICAL PRESS LTD PI LONDON PA 2-4 IDOL LANE, LONDON EC3R 5DD, ENGLAND SN 1359-6535 J9 ANTIVIR THER JI Antivir. Ther. PY 2016 VL 21 SU 1 MA O23 BP A26 EP A26 PG 1 WC Infectious Diseases; Pharmacology & Pharmacy; Virology SC Infectious Diseases; Pharmacology & Pharmacy; Virology GA EE6UF UT WOS:000389747500024 ER PT J AU Mattingly, AS Jones, SE Unsal, AB Purdy, JB Reynolds, J Hazra, R Hadigan, C AF Mattingly, A. S. Jones, S. E. Unsal, A. B. Purdy, J. B. Reynolds, J. Hazra, R. Hadigan, C. TI Decreased bone density among perinatally infected HIV plus adults is related to thymidine analogue exposure: longitudinal evaluation suggests bone density improves over time SO ANTIVIRAL THERAPY LA English DT Meeting Abstract CT 18th International Workshop on Co-Morbidities and Adverse Drug Reactions in HIV CY SEP 12-13, 2016 CL New York, NY C1 [Mattingly, A. S.; Unsal, A. B.; Hadigan, C.] NIAID, Immunoregulat Lab, Bethesda, MD USA. [Jones, S. E.] Leidos Biomed Res Inc, Res Directorate, Clin Monitoring Res Program, Frederick, MD 21702 USA. [Purdy, J. B.] NIH, Crit Care Med Dept, Ctr Clin, Bethesda, MD USA. [Reynolds, J.] NIH, Radiol & Imaging Sci, Div Nucl Med, Ctr Clin, Bethesda, MD USA. [Hazra, R.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU INT MEDICAL PRESS LTD PI LONDON PA 2-4 IDOL LANE, LONDON EC3R 5DD, ENGLAND SN 1359-6535 J9 ANTIVIR THER JI Antivir. Ther. PY 2016 VL 21 SU 1 MA O03 BP A5 EP A5 PG 1 WC Infectious Diseases; Pharmacology & Pharmacy; Virology SC Infectious Diseases; Pharmacology & Pharmacy; Virology GA EE6UF UT WOS:000389747500004 ER PT J AU Mulligan, K Hosek, S Kapogiannis, BG Landovitz, RJ Liu, N Cofield, SS Perumean-Chaney, SE Rutledge, B Havens, PL Wilson, CM AF Mulligan, K. Hosek, S. Kapogiannis, B. G. Landovitz, R. J. Liu, N. Cofield, S. S. Perumean-Chaney, S. E. Rutledge, B. Havens, P. L. Wilson, C. M. CA ATN HIV AIDS Interventions Protocol 11 TI Changes in bone mass after discontinuation of pre-exposure prophylaxis (PrEP) with tenofovir disoproxil fumarate/emtricitabine in young men who have sex with men who lost bone while using PrEP: extension phase results of Adolescent Trials Network Protocol 110 SO ANTIVIRAL THERAPY LA English DT Meeting Abstract CT 18th International Workshop on Co-Morbidities and Adverse Drug Reactions in HIV CY SEP 12-13, 2016 CL New York, NY C1 [Mulligan, K.] Univ Calif San Francisco, San Francisco, CA 94143 USA. [Hosek, S.] John H Stroger Jr Hosp Cook Cty, Chicago, IL USA. [Kapogiannis, B. G.] NICHHD, NIH, Bethesda, MD 20892 USA. [Landovitz, R. J.] Univ Calif Los Angeles, Los Angeles, CA USA. [Liu, N.; Rutledge, B.] Westat Corp, Rockville, MD USA. [Cofield, S. S.; Perumean-Chaney, S. E.; Wilson, C. M.] Univ Alabama Birmingham, Birmingham, AL USA. [Havens, P. L.] Med Coll Wisconsin, Milwaukee, WI 53226 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU INT MEDICAL PRESS LTD PI LONDON PA 2-4 IDOL LANE, LONDON EC3R 5DD, ENGLAND SN 1359-6535 J9 ANTIVIR THER JI Antivir. Ther. PY 2016 VL 21 SU 1 MA O01 BP A3 EP A3 PG 1 WC Infectious Diseases; Pharmacology & Pharmacy; Virology SC Infectious Diseases; Pharmacology & Pharmacy; Virology GA EE6UF UT WOS:000389747500002 ER PT J AU Han, YX He, XM AF Han, Yixing He, Ximiao TI Integrating Epigenomics into the Understanding of Biomedical Insight SO BIOINFORMATICS AND BIOLOGY INSIGHTS LA English DT Article DE epigenetics; computational epigenomics; chromatin; DNA methylation; histone modification; ncRNAs; NGS; integrative analysis ID DIFFERENTIALLY METHYLATED REGIONS; BISULFITE SEQUENCING DATA; LONG NONCODING RNA; CHIP-SEQ DATA; GENOME-WIDE IDENTIFICATION; CHROMATIN-REMODELING COMPLEXES; TRANSCRIPTION FACTOR-BINDING; STEM-CELL DIFFERENTIATION; SMALL-MOLECULE ACTIVATORS; PROTEIN-DNA INTERACTIONS AB Epigenetics is one of the most rapidly expanding fields in biomedical research, and the popularity of the high-throughput next-generation sequencing (NGS) highlights the accelerating speed of epigenomics discovery over the past decade. Epigenetics studies the heritable phenotypes resulting from chromatin changes but without alteration on DNA sequence. Epigenetic factors and their interactive network regulate almost all of the fundamental biological procedures, and incorrect epigenetic information may lead to complex diseases. A comprehensive understanding of epigenetic mechanisms, their interactions, and alterations in health and diseases genome widely has become a priority in biological research. Bioinformatics is expected to make a remarkable contribution for this purpose, especially in processing and interpreting the large-scale NGS datasets. In this review, we introduce the epigenetics pioneering achievements in health status and complex diseases; next, we give a systematic review of the epigenomics data generation, summarize public resources and integrative analysis approaches, and finally outline the challenges and future directions in computational epigenomics. C1 [Han, Yixing] NCI, Mouse Canc Genet Program, Ctr Canc Res, NIH, Frederick, MD 21701 USA. [Han, Yixing] NIDDK, Genet & Biochem Branch, NIH, Bethesda, MD 20892 USA. [He, Ximiao] NCI, Lab Metab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. [He, Ximiao] Huazhong Univ Sci & Technol, Dept Med Genet, Sch Basic Med, Tongji Med Coll, Wuhan, Hubei, Peoples R China. RP Han, YX (reprint author), NCI, Mouse Canc Genet Program, Ctr Canc Res, NIH, Frederick, MD 21701 USA.; Han, YX (reprint author), NIDDK, Genet & Biochem Branch, NIH, Bethesda, MD 20892 USA. EM yi-xing.han@nih.gov NR 354 TC 0 Z9 0 U1 2 U2 2 PU LIBERTAS ACAD PI AUCKLAND PA PO BOX 300-874, ALBANY 0752, AUCKLAND, 00000, NEW ZEALAND SN 1177-9322 J9 BIOINFORM BIOL INSIG JI Bioinform. Biol. Insights PY 2016 VL 10 BP 267 EP 289 DI 10.4137/BBI.S38427 PG 23 WC Biochemical Research Methods SC Biochemistry & Molecular Biology GA EE2AB UT WOS:000389384700001 PM 27980397 ER PT J AU Journy, NM Mchugh, K Harbron, RW Pearce, MS De Gonzalez, AB AF Journy, Neige M. Mchugh, Kieran Harbron, Richard W. Pearce, Mark S. De Gonzalez, Amy Berrington TI Medical conditions associated with the use of CT in children and young adults, Great Britain, 1995-2008 SO BRITISH JOURNAL OF RADIOLOGY LA English DT Article ID COMPUTED-TOMOGRAPHY; SUBSEQUENT RISK; BRAIN-TUMORS; CANCER-RISK; SCANS; COHORT; CHILDHOOD; RADIATION; LEUKEMIA; EXPOSURE AB Objective: To describe the medical conditions associated with the use of CT in children or young adults with no previous cancer diagnosis. Methods: Radiologist reports for scans performed in 1995-2008 in non-cancer patients less than 22 years of age were collected from the radiology information system in 44 hospitals of Great Britain. By semantic search, an automated procedure identified 185 medical conditions within the radiologist reports. Manual validation of a subsample by a paediatric radiologist showed a satisfactory performance of the automatic coding procedure. Results: Medical information was extracted for 37,807 scans; 19.5% scans were performed in children less than 5 years old; 52.0% scans were performed in 2000 or after. Trauma, diseases of the nervous (mainly hydrocephalus) or the circulatory system were each mentioned in 25-30% of scans. Hydrocephalus was mentioned in 19% of all scans, 59% of scans repeated >= 5 times in a year, and was the most frequent condition in children less than 5 years of age. Congenital diseases/malformations, disorders of the musculoskeletal system/connective tissues and infectious or respiratory diseases were each mentioned in 5-10% of scans. Suspicionor diagnosis of benign or malignant tumour was identified in 5% of scans. Conclusion: This study describes the medical conditions that likely underlie the use of CT in children in Great Britain. It shows that patients with hydrocephalus may receive high cumulative radiation exposures from CT in early life, i.e. at ages when they are most sensitive to radiation. Advances in knowledge: The majority of scans were unrelated to cancer suspicion. Repeated scans over time were mainly associated with the management of hydrocephalus. C1 [Journy, Neige M.; De Gonzalez, Amy Berrington] NCI, Radiat Epidemiol Branch, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. [Mchugh, Kieran] Great Ormond St Hosp Sick Children, London, England. [Harbron, Richard W.; Pearce, Mark S.] Newcastle Univ, Royal Victoria Infirm, Sir James Spence Inst, Inst Hlth & Soc, Newcastle Upon Tyne, Tyne & Wear, England. [Harbron, Richard W.; Pearce, Mark S.] Newcastle Univ, NIHR Hlth Protect Res Unit Chem & Radiat Threats, Newcastle Upon Tyne, Tyne & Wear, England. RP Journy, NM (reprint author), NCI, Radiat Epidemiol Branch, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. EM neige.journy@nih.gov FU US National Cancer Institute intramural research program (National Institutes of Health, Bethesda); UK Department of Health; Cancer Research UK FX This study was supported by the US National Cancer Institute intramural research program (National Institutes of Health, Bethesda) and the UK Department of Health and Cancer Research UK. MSP and RWH are affiliated with the National Institute for Health Research (NIHR), Health Protection Research Unit in Chemical and Radiation Threats and Hazards at Newcastle University, in partnership with Public Health England (PHE). The views expressed are those of the authors and not necessarily those of the National Health Service, the NIHR, the UK Department of Health or PHE. NR 28 TC 0 Z9 0 U1 0 U2 0 PU BRITISH INST RADIOLOGY PI LONDON PA 36 PORTLAND PLACE, LONDON W1N 4AT, ENGLAND SN 0007-1285 EI 1748-880X J9 BRIT J RADIOL JI Br. J. Radiol. PY 2016 VL 89 IS 1068 AR 20160532 DI 10.1259/bjr.20160532 PG 41 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA EE1MK UT WOS:000389345900030 PM 27767331 ER PT J AU Conde-Agudelo, A Diaz-Rossello, JL AF Conde-Agudelo, Agustin Diaz-Rossello, Jose L. TI Kangaroo mother care to reduce morbidity and mortality in low birthweight infants SO COCHRANE DATABASE OF SYSTEMATIC REVIEWS LA English DT Review DE Infant Mortality; Infant, Low Birth Weight [growth & development]; Infant, Premature, Diseases [mortality; prevention & control]; Kangaroo-Mother Care Method [methods]; Length of Stay; Physical Stimulation [methods]; Randomized Controlled Trials as Topic; Weight Gain; Humans; Infant, Newborn ID SKIN-TO-SKIN; RANDOMIZED-CONTROLLED-TRIAL; CONVENTIONAL INCUBATOR CARE; PRETERM INFANTS; TRADITIONAL CARE; UTTAR-PRADESH; CONTACT; GROWTH; OUTCOMES; STRESS AB Background Kangaroo mother care (KMC), originally defined as skin-to-skin contact between a mother and her newborn, frequent and exclusive or nearly exclusive breastfeeding, and early discharge from hospital, has been proposed as an alternative to conventional neonatal care for low birthweight (LBW) infants. Objectives To determine whether evidence is available to support the use of KMC in LBW infants as an alternative to conventional neonatal care before or after the initial period of stabilization with conventional care, and to assess beneficial and adverse effects. Search methods We used the standard search strategy of the Cochrane Neonatal Review Group. This included searches in CENTRAL (Cochrane Central Register of Controlled Trials; 2016, Issue 6), MEDLINE, Embase, CINAHL (Cumulative Index to Nursing and Allied Health Literature), LILACS (Latin American and Caribbean Health Science Information database), and POPLINE (Population Information Online) databases (all from inception to June 30, 2016), as well as the WHO (World Health Organization) Trial Registration Data Set (up to June 30, 2016). In addition, we searched the web page of the Kangaroo Foundation, conference and symposia proceedings on KMC, and Google Scholar. Selection criteria Randomized controlled trials comparing KMC versus conventional neonatal care, or early-onset KMC versus late-onset KMC, in LBW infants. Data collection and analysis Data collection and analysis were performed according to the methods of the Cochrane Neonatal Review Group. Main results Twenty-one studies, including 3042 infants, fulfilled inclusion criteria. Nineteen studies evaluated KMC in LBW infants after stabilization, one evaluated KMC in LBW infants before stabilization, and one compared early-onset KMC with late-onset KMC in relatively stable LBW infants. Sixteen studies evaluated intermittent KMC, and five evaluated continuous KMC. KMC versus conventional neonatal care: At discharge or 40 to 41 weeks' postmenstrual age, KMC was associated with a statistically significant reduction in the risk of mortality (risk ratio [RR] 0.60, 95% confidence interval [CI] 0.39 to 0.92; eight trials, 1736 infants), nosocomial infection/sepsis (RR 0.35, 95% CI 0.22 to 0.54; five trials, 1239 infants), and hypothermia (RR 0.28, 95% CI 0.16 to 0.49; nine trials, 989 infants; moderate-quality evidence). At latest follow-up, KMC was associated with a significantly decreased risk of mortality (RR 0.67, 95% CI 0.48 to 0.95; 12 trials, 2293 infants; moderate-quality evidence) and severe infection/sepsis (RR 0.50, 95% CI 0.36 to 0.69; eight trials, 1463 infants; moderate-quality evidence). Moreover, KMC was found to increase weight gain (mean difference [MD] 4.1 g/d, 95% CI 2.3 to 5.9; 11 trials, 1198 infants; moderate-quality evidence), length gain (MD 0.21 cm/week, 95% CI 0.03 to 0.38; three trials, 377 infants) and head circumference gain (MD 0.14 cm/week, 95% CI 0.06 to 0.22; four trials, 495 infants) at latest follow-up, exclusive breastfeeding at discharge or 40 to 41 weeks' postmenstrual age (RR 1.16, 95% CI 1.07 to 1.25; six studies, 1453 mothers) and at one to three months' follow-up (RR 1.20, 95% CI 1.01 to 1.43; five studies, 600 mothers), any (exclusive or partial) breastfeeding at discharge or at 40 to 41 weeks' postmenstrual age (RR 1.20, 95% CI 1.07 to 1.34; 10 studies, 1696 mothers; moderate-quality evidence) and at one to three months' follow-up (RR 1.17, 95% CI 1.05 to 1.31; nine studies, 1394 mothers; low-quality evidence), and some measures of mother-infant attachment and home environment. No statistically significant differences were found between KMC infants and controls in Griffith quotients for psychomotor development at 12 months' corrected age (low-quality evidence). Sensitivity analysis suggested that inclusion of studies with high risk of bias did not affect the general direction of findings nor the size of the treatment effect for main outcomes. Early-onset KMC versus late-onset KMC in relatively stable infants: One trial compared early-onset continuous KMC (within 24 hours post birth) versus late-onset continuous KMC (after 24 hours post birth) in 73 relatively stable LBW infants. Investigators reported no significant differences between the two study groups in mortality, morbidity, severe infection, hypothermia, breastfeeding, and nutritional indicators. Early-onset KMC was associated with a statistically significant reduction in length of hospital stay (MD 0.9 days, 95% CI 0.6 to 1.2). Authors' conclusions Evidence from this updated review supports the use of KMC in LBW infants as an alternative to conventional neonatal care, mainly in resource-limited settings. Further information is required concerning the effectiveness and safety of early-onset continuous KMC in unstabilized or relatively stabilized LBW infants, as well as long-term neurodevelopmental outcomes and costs of care. C1 [Conde-Agudelo, Agustin] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Perinatol Res Branch, NIH, US Dept HHS, Bethesda, MD 20892 USA. [Conde-Agudelo, Agustin] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Perinatol Res Branch, NIH, Detroit, MI 48202 USA. [Conde-Agudelo, Agustin] Wayne State Univ, Dept Obstet & Gynecol, Detroit, MI 48202 USA. [Diaz-Rossello, Jose L.] Hosp Clin Montevideo, Dept Neonatol, Montevideo, Uruguay. RP Conde-Agudelo, A (reprint author), Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Perinatol Res Branch, NIH, US Dept HHS, Bethesda, MD 20892 USA.; Conde-Agudelo, A (reprint author), Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Perinatol Res Branch, NIH, Detroit, MI 48202 USA.; Conde-Agudelo, A (reprint author), Wayne State Univ, Dept Obstet & Gynecol, Detroit, MI 48202 USA. EM condeagu@hotmail.com FU Perinatology Research Branch, Eunice Kennedy Shriver National Institute of Child Health and Human Development/National Institutes of Health/Department of Health and Human Services, Bethesda, MD, and Detroit, MI; Department of Obstetrics and Gynecology, Wayne State University, Detroit, MI, USA; Departamento de Neonatologia del Hospital de Clinicas, Universidad de la Republica, Montevideo, Uruguay FX Internal sources; (AC-A) Perinatology Research Branch, Eunice Kennedy Shriver National Institute of Child Health and Human Development/National Institutes of Health/Department of Health and Human Services, Bethesda, MD, and Detroit, MI, and Department of Obstetrics and Gynecology, Wayne State University, Detroit, MI, USA.; (JLD-R) Departamento de Neonatologia del Hospital de Clinicas, Universidad de la Republica, Montevideo, Uruguay. NR 107 TC 1 Z9 1 U1 4 U2 4 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1469-493X EI 1361-6137 J9 COCHRANE DB SYST REV JI Cochrane Database Syst Rev. PY 2016 IS 8 AR CD002771 DI 10.1002/14651858.CD002771.pub4 PG 153 WC Medicine, General & Internal SC General & Internal Medicine GA EE4TK UT WOS:000389598000007 PM 27552521 ER PT J AU Turan, I Hutchins, BI Hacihamdioglu, B Ozbek, MN Kotan, LD Ozkan, Y Stoner, H Cheng, PJ Gurbuz, F Mengen, E Yuksel, B Wray, S Topaloglu, K AF Turan, Ihsan Hutchins, B. Ian Hacihamdioglu, Bulent Ozbek, Mehmet Nuri Kotan, Leman Damla Ozkan, Yusuf Stoner, Hudson Cheng, Paul J. Gurbuz, Fatih Mengen, Eda Yuksel, Bilgin Wray, Susan Topaloglu, Kemal TI Inactivating Mutations in CCDC141 Causing Idiopathic Hypogonadotrophic Hypogonadism/Kallmann Syndrome SO HORMONE RESEARCH IN PAEDIATRICS LA English DT Meeting Abstract C1 [Turan, Ihsan; Kotan, Leman Damla; Gurbuz, Fatih; Mengen, Eda; Yuksel, Bilgin; Topaloglu, Kemal] Cukurova Univ, Div Pediat Endocrinol, Adana, Turkey. [Hutchins, B. Ian; Stoner, Hudson; Cheng, Paul J.; Wray, Susan] NINDS, Cellular & Dev Neurobiol Sect, Bldg 36,Rm 4D04, Bethesda, MD 20892 USA. [Hacihamdioglu, Bulent] GATA Med Fac, Dept Pediat Endocrinol, Istanbul, Turkey. [Ozbek, Mehmet Nuri] Diyarbakir Childrens State Hosp, Dept Pediat Endocrinol, Diyarbakir, Turkey. [Ozkan, Yusuf] Firat Univ, Dept Endocrinol, Elazig, Turkey. NR 0 TC 0 Z9 0 U1 0 U2 0 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 1663-2818 EI 1663-2826 J9 HORM RES PAEDIAT JI Horm. Res. Paediatr. PY 2016 VL 86 SU 1 MA FC12.3 BP 58 EP 58 PG 1 WC Endocrinology & Metabolism; Pediatrics SC Endocrinology & Metabolism; Pediatrics GA DX1ZQ UT WOS:000384166800138 ER PT J AU Gkourogianni, A Andrew, M Crocker, M Dunbar, N Jorge, A Lafranchi, S Lalani, S Lebl, J Lin, L Los, E Newbern, D Nowak, C Olson, M Popovic, J Pruhova, S Quintos, JB Sentchordi, L Baron, J Nilsson, O Dauber, A AF Gkourogianni, Alexandra Andrew, Melissa Crocker, Melissa Dunbar, Nancy Jorge, Alexander Lafranchi, Stephen Lalani, Seema Lebl, Jan Lin, Lynda Los, Evan Newbern, Dorothee Nowak, Catherine Olson, Micah Popovic, Jadranka Pruhova, Stepanka Quintos, Jose Bernardo Sentchordi, Lucia Baron, Jeffrey Nilsson, Ola Dauber, Andrew TI Clinical Characterization of Children with Autosomal Dominant Short Stature due to Aggrecan Mutations Broadens the Phenotypic Spectrum SO HORMONE RESEARCH IN PAEDIATRICS LA English DT Meeting Abstract C1 [Gkourogianni, Alexandra; Nilsson, Ola] Karolinska Inst, Stockholm, Sweden. [Andrew, Melissa; Dauber, Andrew] Cincinnati Childrens Hosp Med Ctr, Cincinnati, OH 45229 USA. [Crocker, Melissa; Nowak, Catherine] Boston Childrens Hosp, Boston, MA USA. [Dunbar, Nancy] Connecticut Childrens Hosp, Hartford, CT USA. [Sentchordi, Lucia] Hosp Univ La Paz, Madrid, Spain. [Jorge, Alexander] Univ Sao Paulo, Sao Paulo, Brazil. [Lafranchi, Stephen; Los, Evan] Oregon Hlth & Sci Univ, Portland, OR 97201 USA. [Lalani, Seema; Lin, Lynda] Texas Childrens Hosp, Houston, TX 77030 USA. [Lebl, Jan] Charles Univ Prague, Prague, Czech Republic. [Newbern, Dorothee; Olson, Micah] Phoenix Childrens Hosp, Phoenix, AZ USA. [Popovic, Jadranka] Childrens Hosp Pittsburgh, Pittsburgh, PA 15213 USA. [Pruhova, Stepanka; Quintos, Jose Bernardo] Hasbro Childrens Hosp, Providence, RI USA. [Baron, Jeffrey] NICHHD, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 1663-2818 EI 1663-2826 J9 HORM RES PAEDIAT JI Horm. Res. Paediatr. PY 2016 VL 86 SU 1 MA FC14.1 BP 63 EP 63 PG 1 WC Endocrinology & Metabolism; Pediatrics SC Endocrinology & Metabolism; Pediatrics GA DX1ZQ UT WOS:000384166800148 ER PT J AU Gaughan, T Buckley, A Hommer, R Grant, P Williams, K Leckman, JF Swedo, SE AF Gaughan, Thomas Buckley, Ashura Hommer, Rebecca Grant, Paul Williams, Kyle Leckman, James F. Swedo, Susan E. TI Rapid Eye Movement Sleep Abnormalities in Children with Pediatric Acute-Onset Neuropsychiatric Syndrome (PANS) SO JOURNAL OF CLINICAL SLEEP MEDICINE LA English DT Article DE obsessive compulsive disorder; PANS; polysomnography; REM sleep behavior disorder ID ATTENTION-DEFICIT/HYPERACTIVITY DISORDER; BEHAVIOR DISORDER; REM-SLEEP; METAANALYSIS; CHILDHOOD AB Study Objectives: Polysomnographic investigation of sleep architecture in children presenting with pediatric acute-onset neuropsychiatric syndrome (PANS). Methods: Fifteen consecutive subjects meeting criteria for PANS (mean age = 7.2 y; range 3-10 y) underwent single-night full polysomnography (PSG) read by a pediatric neurologist. Results: Thirteen of 15 subjects (87%) had abnormalities detected with PSG. Twelve of 15 had evidence of rapid eye movement (REM) sleep motor disinhibition, as characterized by excessive movement, laughing, hand stereotypies, moaning, or the continuation of periodic limb movements during sleep (PLMS) into REM sleep. Conclusions: This study shows various forms of REM sleep motor disinhibition present in a population of children with PANS. C1 [Gaughan, Thomas; Buckley, Ashura; Hommer, Rebecca; Grant, Paul; Swedo, Susan E.] NIMH, Dept Pediat & Dev Neurosci, Bethesda, MD 20892 USA. [Williams, Kyle] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Pediat Neuropsychiat & Immunol Program, Boston, MA USA. [Leckman, James F.] Yale Univ, Sch Med, Ctr Child Study, New Haven, CT 06510 USA. RP Buckley, A (reprint author), NIMH, Dept Pediat & Dev Neurosci, Bethesda, MD 20892 USA. EM shu.buckley@nih.gov FU Intramural Research Program of the National Institute of Mental Health [MH002666, NCT01281969, 11-M-0058, NCT01778504, 13-M-0028]; NIH; Tourette Syndrome Association; Grifols LLC; Klingenstein Third Generation Foundation FX This was not an industry supported study. Support for this project was provided by the Intramural Research Program of the National Institute of Mental Health MH002666 (NCT01281969, protocol 11-M-0058 and NCT01778504, protocol 13-M-0028). Dr. Leckman has received support from the NIH (salary and research funding), Tourette Syndrome Association (research funding), Grifols LLC (research funding) and Klingenstein Third Generation Foundation (medical student fellowship program); he receives book royalties from John Wiley and Sons, McGraw-Hill, and Oxford University Press. The other authors have indicated no financial conflicts of interest. The remaining authors indicate no financial conflicts of interest. NR 33 TC 1 Z9 1 U1 4 U2 4 PU AMER ACAD SLEEP MEDICINE PI DARIEN PA 2510 N FRONTAGE RD, DARIEN, IL 60561 USA SN 1550-9389 EI 1550-9397 J9 J CLIN SLEEP MED JI J. Clin. Sleep Med. PY 2016 VL 12 IS 7 BP 1027 EP 1032 DI 10.5664/jcsm.5942 PG 6 WC Clinical Neurology SC Neurosciences & Neurology GA EF0AQ UT WOS:000389988200014 PM 27166296 ER PT J AU Nahin, RL AF Nahin, Richard L. TI Categorizing the severity of pain using questions from the 2012 National Health Interview Survey SO JOURNAL OF PAIN RESEARCH LA English DT Article DE cross-sectional study; pain frequency; pain severity; MANOVA ID LOW-BACK-PAIN; CUT-POINTS; OLDER-PEOPLE; NECK PAIN; DISABILITY; CARE; POPULATION; PREVALENCE; COMMUNITY; MODERATE AB Background: Based on qualitative and mixed-method approaches, Miller and Loeb have proposed a coding system that combines questions on pain persistence and bothersomeness to create discrete categories of increasing pain severity for use in large population-based surveys. In the current analyses, using data from the 2012 National Health Interview Survey, we quantitatively assess the pain category definitions proposed by Miller and Loeb and compare this original definition to ten alternative definitions. Methods: Using multivariate analysis of variance, each definition was related simultaneously to four dependent measures-the Kessler 6 score for measuring psychological distress, the number of health-related bed-disability days, the number of visits to a health professional, and the number of emergency room visits. Following the protocol of Serlin et al, the definition yielding the largest F score was considered the optimal definition. Results: The Miller and Loeb definition produced the largest F value (185.87), followed consecutively by several alternative definitions #5 (184.17), #10 (180.95), and #9 (179.5). A nearly identical ordering was found when looking at the mean F value generated from 100 random samples. We also examined the frequencies with which each alternative definition achieved the optimal F value over the 100 random samples. Only two definitions had achieved the optimal F value > 5% of the time: the Miller and Loeb definition was optimal 46% of the time, while alternative definition #5 was optimal 41% of the time. Similar results were seen in subpopulations with back pain and joint pain. Conclusion: Additional support was provided for the Miller and Loeb coding of pain persistence and bothersomeness to produce discrete categories of increasing pain severity. This two-question coding scheme may prove to be a viable option for assessing pain severity in clinical settings where clinician time and patient burden are limiting factors. C1 [Nahin, Richard L.] Natl Inst Hlth, Natl Ctr Complementary & Integrat Hlth, 6707 Democracy Blvd,Suite 401, Bethesda, MD 20892 USA. RP Nahin, RL (reprint author), Natl Inst Hlth, Natl Ctr Complementary & Integrat Hlth, 6707 Democracy Blvd,Suite 401, Bethesda, MD 20892 USA. EM nahinr@mail.nih.gov NR 20 TC 1 Z9 1 U1 1 U2 2 PU DOVE MEDICAL PRESS LTD PI ALBANY PA PO BOX 300-008, ALBANY, AUCKLAND 0752, NEW ZEALAND SN 1178-7090 J9 J PAIN RES JI J. Pain Res. PY 2016 VL 9 BP 105 EP 113 DI 10.2147/JPR.S99548 PG 9 WC Clinical Neurology SC Neurosciences & Neurology GA EE7CG UT WOS:000389771600002 PM 27042138 ER PT J AU Wilsey, BL Deutsch, R Samara, E Marcotte, TD Barnes, AJ Huestis, MA Le, D AF Wilsey, Barth L. Deutsch, Reena Samara, Emil Marcotte, Thomas D. Barnes, Allan J. Huestis, Marilyn A. Le, Danny TI A preliminary evaluation of the relationship of cannabinoid blood concentrations with the analgesic response to vaporized cannabis SO JOURNAL OF PAIN RESEARCH LA English DT Article ID NEUROPATHIC PAIN SCALE; MAJOR PHYTOCANNABINOIDS; CONTROLLED-TRIAL; MARIJUANA SMOKE; CLINICAL-TRIALS; DELTA-9-TETRAHYDROCANNABINOL; PHARMACOKINETICS; HUMANS; TETRAHYDROCANNABINOL; DISPOSITION C1 [Wilsey, Barth L.; Le, Danny] VA Northern Calif Hlth Care Syst, Mather, CA USA. [Wilsey, Barth L.; Le, Danny] Univ Calif Sacramento, Dept Phys Med & Rehabil, Sacramento, CA USA. [Deutsch, Reena; Marcotte, Thomas D.] Univ Calif San Diego, Dept Psychiat, La Jolla, CA 92093 USA. [Samara, Emil] PharmaPolaris Int, Davis, CA USA. [Barnes, Allan J.; Huestis, Marilyn A.] NIDA, Chem & Drug Metab, IRP, Baltimore, MD USA. [Huestis, Marilyn A.] Univ Maryland, Sch Med, Baltimore, MD 21201 USA. RP Wilsey, BL (reprint author), Univ Calif San Diego, UC Ctr Med Cannabis Res, 220 Dickinson St,Suite B, San Diego, CA 92103 USA. EM bwilsey@ucsd.edu FU UC Center for Medicinal Cannabis Research; NIDA of the National Institutes of Health [R01DA030424] FX Research reported in this publication was supported by the UC Center for Medicinal Cannabis Research and the NIDA of the National Institutes of Health under award number R01DA030424. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health or the Department of Veterans Affairs. NR 56 TC 0 Z9 0 U1 0 U2 0 PU DOVE MEDICAL PRESS LTD PI ALBANY PA PO BOX 300-008, ALBANY, AUCKLAND 0752, NEW ZEALAND SN 1178-7090 J9 J PAIN RES JI J. Pain Res. PY 2016 VL 9 BP 587 EP 598 PG 12 WC Clinical Neurology SC Neurosciences & Neurology GA EE7VL UT WOS:000389832800001 PM 27621666 ER PT J AU Artym, VV AF Artym, Vira V. TI Dense fibrillar collagen is a master activator of invadopodia SO MOLECULAR & CELLULAR ONCOLOGY LA English DT Article DE Cell-matrix interactions; dense fibrillar collagen; desmoplasia; extracellular matrix; invadopodia; invadosomes; integrin; metastasis AB Tumor stroma is characterized by abnormal accumulation of dense fibrillar collagen, which promotes tumor progression and metastasis. However, the effect of desmoplastic collagen on cells has been unclear. Our recent findings demonstrate that dense fibrillar collagen activates a novel phosphosignaling mechanism for robust induction of invadopodia in tumor cells and normal fibroblasts. C1 [Artym, Vira V.] Natl Inst Dent & Craniofacial Res, Lab Cell & Dev Biol, NIH, Bethesda, MD 20892 USA. RP Artym, VV (reprint author), Natl Inst Dent & Craniofacial Res, Lab Cell & Dev Biol, NIH, Bethesda, MD 20892 USA. EM vartym@mail.nih.gov NR 10 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 2372-3556 EI 2372-3548 J9 MOL CELL ONCOL JI MOL. CELL ONCOL. PY 2016 VL 3 IS 3 AR UNSP e1035476 DI 10.1080/23723556.2015.1035476 PG 3 WC Oncology SC Oncology GA ED9GJ UT WOS:000389177900009 PM 27314068 ER PT J AU Alger, JR Ellingson, BM Ashe-McNalley, C Woodworth, DC Labus, JS Farmer, M Huang, L Apkarian, AV Johnson, KA Mackey, SC Ness, TJ Deutsch, G Harris, RE Clauw, DJ Glover, GH Parrish, TB den Hollander, J Kusek, JW Mullins, C Mayer, EA AF Alger, Jeffry R. Ellingson, Benjamin M. Ashe-McNalley, Cody Woodworth, Davis C. Labus, Jennifer S. Farmer, Melissa Huang, Lejian Apkarian, A. Vania Johnson, Kevin A. Mackey, Sean C. Ness, Timothy J. Deutsch, Georg Harris, Richard E. Clauw, Daniel J. Glover, Gary H. Parrish, Todd B. den Hollander, Jan Kusek, John W. Mullins, Chris Mayer, Emeran A. CA MAPP Res Network Investigators TI Multisite, multimodal neuroimaging of chronic urological pelvic pain: Methodology of the MAPP Research Network SO NEUROIMAGE-CLINICAL LA English DT Article DE Urologic chronic pelvic pain syndromes; Brain; Magnetic resonance imaging; Functional magnetic resonance imaging; Diffusion tensor imaging; DTI; TransMAPP ID CYSTITIS/PAINFUL BLADDER SYNDROME; ALZHEIMERS-DISEASE; MULTICENTER FMRI; RESTING-STATE; HUMAN BRAIN; MRI; REGISTRATION; VARIABILITY; RELIABILITY; ACTIVATION AB The Multidisciplinary Approach to the Study of Chronic Pelvic Pain (MAPP) Research Network is an ongoing multi-center collaborative research group established to conduct integrated studies in participants with urologic chronic pelvic pain syndrome (UCPPS). The goal of these investigations is to provide new insights into the etiology, natural history, clinical, demographic and behavioral characteristics, search for new and evaluate candidate biomarkers, systematically test for contributions of infectious agents to symptoms, and conduct animal studies to understand underlying mechanisms for UCPPS. Study participants were enrolled in a one-year observational study and evaluated through a multisite, collaborative neuroimaging study to evaluate the association between UCPPS and brain structure and function. 3D T1-weighted structural images, resting-state fMRI, and high angular resolution diffusion MRI were acquired in five participating MAPP Network sites using 8 separate MRI hardware and software configurations. We describe the neuroimaging methods and procedures used to scan participants, the challenges encountered in obtaining data from multiple sites with different equipment/software, and our efforts to minimize site-to-site variation. Published by Elsevier Inc. C1 [Alger, Jeffry R.] Univ Calif Los Angeles, David Geffen Sch Med, Dept Neurol, Los Angeles, CA 90095 USA. [Alger, Jeffry R.; Ellingson, Benjamin M.; Woodworth, Davis C.] Univ Calif Los Angeles, David Geffen Sch Med, Dept Radiol Sci, Los Angeles, CA 90095 USA. [Alger, Jeffry R.; Ellingson, Benjamin M.; Woodworth, Davis C.] Univ Calif Los Angeles, David Geffen Sch Med, Dept Biomed Phys, Los Angeles, CA 90095 USA. [Alger, Jeffry R.; Ellingson, Benjamin M.; Labus, Jennifer S.; Mayer, Emeran A.] Univ Calif Los Angeles, David Geffen Sch Med, UCLA Brain Res Inst, Los Angeles, CA 90095 USA. [Alger, Jeffry R.; Mayer, Emeran A.] Univ Calif Los Angeles, David Geffen Sch Med, UCLA Ahmanson Lovelace Brain Mapping Ctr, Los Angeles, CA 90095 USA. [Alger, Jeffry R.] NeuroSpectroScopics LLC, Sherman, CA USA. [Ashe-McNalley, Cody; Labus, Jennifer S.; Mayer, Emeran A.] Univ Calif Los Angeles, David Geffen Sch Med, Dept Internal Med, Los Angeles, CA 90095 USA. [Ellingson, Benjamin M.; Ashe-McNalley, Cody; Woodworth, Davis C.; Labus, Jennifer S.; Mayer, Emeran A.] Univ Calif Los Angeles, David Geffen Sch Med, Oppenheimer Ctr Neurobiol Stress, 10833 Le Conte Ave,CHS 42-210 MC 737818, Los Angeles, CA 90095 USA. [Ellingson, Benjamin M.] Univ Calif Los Angeles, Henry Samueli Sch Engn & Appl Sci, Dept Bioengn, Los Angeles, CA 90024 USA. [Ellingson, Benjamin M.; Mayer, Emeran A.] Univ Calif Los Angeles, David Geffen Sch Med, Dept Psychiat & Biobehav Sci, Los Angeles, CA 90095 USA. [Farmer, Melissa; Huang, Lejian; Apkarian, A. Vania] Northwestern Univ, Feinberg Sch Med, Dept Physiol, 300 E Super St, Chicago, IL 60611 USA. [Apkarian, A. Vania] Northwestern Univ, Feinberg Sch Med, Dept Anesthesia, 300 E Super St, Chicago, IL 60611 USA. [Apkarian, A. Vania] Northwestern Univ, Feinberg Sch Med, Dept Surg, 300 E Super St, Chicago, IL 60611 USA. [Johnson, Kevin A.; Mackey, Sean C.] Stanford Univ, Dept Neurol, Palo Alto, CA 94304 USA. [Ness, Timothy J.] Univ Alabama Birmingham, Dept Anesthesiol, Birmingham, AL USA. [Deutsch, Georg] Univ Alabama Birmingham, Dept Radiol, Birmingham, AL USA. [Harris, Richard E.; Clauw, Daniel J.] Univ Michigan, Dept Anesthesiol, Ann Arbor, MI 48109 USA. [Glover, Gary H.] Stanford Univ, Dept Radiol, Palo Alto, CA 94304 USA. [Parrish, Todd B.] Northwestern Univ, Dept Radiol, Chicago, IL 60611 USA. [den Hollander, Jan] Univ Alabama Birmingham, Dept Radiol, Birmingham, AL USA. [Kusek, John W.; Mullins, Chris] NIDDK, Div Kidney Urol & Hematol Dis, NIH, Bethesda, MD 20892 USA. RP Mayer, EA (reprint author), Univ Calif Los Angeles, David Geffen Sch Med, Oppenheimer Ctr Neurobiol Stress, 10833 Le Conte Ave,CHS 42-210 MC 737818, Los Angeles, CA 90095 USA. EM emayer@ucla.edu FU National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK), National Institutes of Health (NIH) [DK82370, DK82342, DK82315, DK82344, DK82325, DK82345, DK82333, DK82316]; [R01 DK048351] FX Funding for the MAPP Research Network was obtained under cooperative agreements from the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK), National Institutes of Health (NIH) DK82370, DK82342, DK82315, DK82344, DK82325, DK82345, DK82333, and DK82316, and in part from R01 DK048351 (EAM). NR 46 TC 1 Z9 1 U1 1 U2 1 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 2213-1582 J9 NEUROIMAGE-CLIN JI NeuroImage-Clin. PY 2016 VL 12 BP 65 EP 77 DI 10.1016/j.nicl.2015.12.009 PG 13 WC Neuroimaging SC Neurosciences & Neurology GA EF3AI UT WOS:000390196400009 PM 27408791 ER PT J AU Dworkin, JD Sweeney, EM Schindler, MK Chahin, S Reich, DS Shinohara, RT AF Dworkin, Jordan D. Sweeney, Elizabeth M. Schindler, Matthew K. Chahin, Salim Reich, Daniel S. Shinohara, Russell T. TI PREVAIL: Predicting Recovery through Estimation and Visualization of Active and Incident Lesions SO NEUROIMAGE-CLINICAL LA English DT Article DE Multiple sclerosis; Prediction; Lesion; Neuroimaging; MRI ID MULTIPLE-SCLEROSIS LESIONS; MAGNETIZATION-TRANSFER MR; WHITE-MATTER; BRAIN; REMYELINATION; DEMYELINATION; SEGMENTATION; DISABILITY; PATTERNS; INSIGHTS AB Objective: The goal of this studywas to develop amodel that integrates imaging and clinical information observed at lesion incidence for predicting the recovery of white matter lesions in multiple sclerosis (MS) patients. Methods: Demographic, clinical, and magnetic resonance imaging (MRI) data were obtained from 60 subjects with MS as part of a natural history study at the National Institute of Neurological Disorders and Stroke. A total of 401 lesions met the inclusion criteria and were used in the study. Imaging features were extracted from the intensity-normalized T1-weighted (T1w) and T2-weighted sequences as well as magnetization transfer ratio (MTR) sequence acquired at lesion incidence. T1wand MTR signatureswere also extracted fromimages acquired one-year post-incidence. Imaging featureswere integratedwith clinical and demographic data observed at lesion incidence to create statistical prediction models for long-term damage within the lesion. Validation: The performance of the T1w and MTR predictions was assessed in two ways: first, the predictive accuracy was measured quantitatively using leave-one-lesion-out cross-validated (CV) mean-squared predictive error. Then, to assess the prediction performance from the perspective of expert clinicians, three board-certified MS clinicians were asked to individually score how similar the CV model-predicted one-year appearance was to the true one-year appearance for a random sample of 100 lesions. Results: The cross-validated root-mean-square predictive error was 0.95 for normalized T1w and 0.064 for MTR, compared to the estimated measurement errors of 0.48 and 0.078 respectively. The three expert raters agreed that T1w and MTR predictions closely resembled the true one-year follow-up appearance of the lesions in both degree and pattern of recovery within lesions. Conclusion: This study demonstrates that by using only information from a single visit at incidence, we can predict how a new lesion will recover using relatively simple statistical techniques. The potential to visualize the likely course of recovery has implications for clinical decision-making, as well as trial enrichment. (C) 2016 The Authors. Published by Elsevier Inc. This is an open access article under the CC BY-NC-ND license. C1 [Dworkin, Jordan D.; Shinohara, Russell T.] Univ Penn, Dept Biostat & Epidemiol, Perelman Sch Med, Philadelphia, PA 19104 USA. [Sweeney, Elizabeth M.; Reich, Daniel S.] Johns Hopkins Univ, Dept Biostat, Bloomberg Sch Publ Hlth, Baltimore, MD 21205 USA. [Schindler, Matthew K.; Reich, Daniel S.] Natl Inst Neurol Dis & Stroke, Translat Neuroradiol Unit, Div Neuroimmunol & Neurovirol, NIH, Bethesda, MD 20892 USA. [Chahin, Salim] Univ Penn, Dept Neurol, Multiple Sclerosis Div, Perelman Sch Med, Philadelphia, PA 19104 USA. RP Dworkin, JD (reprint author), Univ Penn, Dept Biostat & Epidemiol, Perelman Sch Med, Philadelphia, PA 19104 USA. EM jdwor@mail.med.upenn.edu OI Dworkin, Jordan/0000-0002-5720-1298 FU NIH from the National Institute of Neurological Disorders and Stroke (NINDS) [RO1 NS085211, R21 NS093349]; Intramural Research Program of NINDS FX The authors would like to thank Blake Dewey, the Neuroimmunology Branch clinical group and the technicians at the NIH who were instrumental in helping to collect and process the study data. The project described is supported in part by the NIH grants RO1 NS085211 and R21 NS093349 from the National Institute of Neurological Disorders and Stroke (NINDS). The research is also supported by the Intramural Research Program of NINDS. The content is solely the responsibility of the authors and does not necessarily represent the official views of the funding agencies. NR 31 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 2213-1582 J9 NEUROIMAGE-CLIN JI NeuroImage-Clin. PY 2016 VL 12 BP 293 EP 299 DI 10.1016/j.nicl.2016.07.015 PG 7 WC Neuroimaging SC Neurosciences & Neurology GA EF3AI UT WOS:000390196400034 PM 27551666 ER PT J AU Suttner, LH Mejia, A Dewey, B Sati, P Reich, DS Shinohara, RT AF Suttner, Leah H. Mejia, Amanda Dewey, Blake Sati, Pascal Reich, Daniel S. Shinohara, Russell T. TI Statistical estimation of white matter microstructure from conventional MRI SO NEUROIMAGE-CLINICAL LA English DT Article DE Image synthesis ID DEEP GRAY-MATTER; MULTIPLE-SCLEROSIS; DIFFUSION TENSOR; ALZHEIMERS-DISEASE; T2 HYPOINTENSITY; COGNITIVE IMPAIRMENT; BRAIN; MULTICENTER; DISABILITY; DEGENERATION AB Diffusion tensor imaging (DTI) has become the predominant modality for studying white matter integrity in multiple sclerosis (MS) and other neurological disorders. Unfortunately, the use of DTI-based biomarkers in large multi-center studies is hindered by systematic biases that confound the study of disease-related changes. Furthermore, the site-to-site variability in multi-center studies is significantly higher for DTI than that for conventional MRI-based markers. In our study, we apply the Quantitative MR Estimation Employing Normalization (QuEEN) model to estimate the four DTI measures: MD, FA, RD, and AD. QuEEN uses a voxel-wise generalized additive regression model to relate the normalized intensities of one or more conventional MRI modalities to a quantitative modality, such as DTI. We assess the accuracy of the models by comparing the prediction error of estimated DTI images to the scan-rescan error in subjects with two sets of scans. Across the four DTI measures, the performance of the models is not consistent: Both MD and RD estimations appear to be quite accurate, while AD estimation is less accurate than MD and RD; the accuracy of FA estimation is poor. Thus, in some cases when assessing white matter integrity, it may be sufficient to acquire conventional MRI sequences alone. (C) 2016 The Authors. Published by Elsevier Inc. C1 [Suttner, Leah H.; Shinohara, Russell T.] Univ Penn, Perelman Sch Med, Dept Biostat & Epidemiol, Philadelphia, PA 19104 USA. [Mejia, Amanda; Reich, Daniel S.] Johns Hopkins Univ, Dept Biostat, Baltimore, MD 21205 USA. [Dewey, Blake; Sati, Pascal; Reich, Daniel S.] NINDS, Translat Neuroradiol Unit, Div Neuroimmunol & Neurovirol, NIH, Bldg 36,Rm 4D04, Bethesda, MD 20892 USA. RP Suttner, LH (reprint author), Univ Penn, Perelman Sch Med, Dept Biostat & Epidemiol, Philadelphia, PA 19104 USA. EM lsutt@mail.med.upenn.edu FU NIH from the National Institute of Neurological Disorders and Stroke (NINDS) [RO1 NS085211, Z01-NS003119]; Intramural Research Program of NINDS; [R21 NS093349] FX We thank Dr. Govind Nair for his insightful comments and discussions about this work. We acknowledge the contribution of the NINDS Neuroimmunology Clinic, which recruited the patients and performed clinical evaluations, and the NIH Functional MRI Facility, where scanning took place. Suttner, Mejia, and Shinohara are partially funded by the NIH grant RO1 NS085211 from the National Institute of Neurological Disorders and Stroke (NINDS) (Z01-NS003119). Shinohara was also partially funded by R21 NS093349. The study was supported in part by the Intramural Research Program of NINDS. This work represents the opinions of the researchers and not necessarily that of the granting organizations. NR 43 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 2213-1582 J9 NEUROIMAGE-CLIN JI NeuroImage-Clin. PY 2016 VL 12 BP 615 EP 623 DI 10.1016/j.nicl.2016.09.010 PG 9 WC Neuroimaging SC Neurosciences & Neurology GA EF3AI UT WOS:000390196400070 PM 27722085 ER PT J AU Floeter, MK Bageac, D Danielian, LE Braun, LE Traynor, BJ Kwan, JY AF Floeter, Mary Kay Bageac, Devin Danielian, Laura E. Braun, Laura E. Traynor, Bryan J. Kwan, Justin Y. TI Longitudinal imaging in C9orf72 mutation carriers: Relationship to phenotype SO NEUROIMAGE-CLINICAL LA English DT Article DE C9orf72; Amyotrophic lateral sclerosis; Frontotemporal dementia; Diffusion tensor imaging; Cortical thickness; Ventricular volume ID AMYOTROPHIC-LATERAL-SCLEROSIS; GENETIC FRONTOTEMPORAL DEMENTIA; HUMAN CEREBRAL-CORTEX; HEXANUCLEOTIDE REPEAT EXPANSION; MAGNETIC-RESONANCE IMAGES; SURFACE-BASED ANALYSIS; RATING-SCALE; ALS; BRAIN; MRI AB Expansion mutations in the C9orf72 gene may cause amyotrophic lateral sclerosis (ALS), frontotemporal dementia (FTD), or mixtures of the two clinical phenotypes. Different imaging findings have been described for C9orf72-associated diseases in comparison with sporadic patients with the same phenotypes, but it is uncertain whether different phenotypes have a common genotype-associated imaging signature. To address this question, 27 unrelated C9orf72 expansion mutation carriers (C9+) with varied phenotypes, 28 age-matched healthy controls and 22 patients with sporadic ALS (sALS) underwent 3T MRI scanning and clinical phenotyping. Measures of brain volumes and cortical thickness were extracted from T1 images. Compared to healthy controls and sALS patients, symptomatic C9+ subjects had greater ventricular volume loss and thalamic atrophy for age, with diffuse, patchy cortical thinning. Asymptomatic carriers did not differ from controls. C9+ ALS and ALS-FTD patients had less thinning of the motor cortex than sALS patients, but more thinning in extramotor regions, particularly in frontal and temporal lobes. C9+ ALS patients differed from sporadic ALS patients in the thickness of the superior frontal gyrus and lateral orbitofrontal cortex. Thickness of the precentral gyrus was weakly correlated with the revised ALS functional rating scale. Thickness of many cortical regions, including several frontal and temporal regions, was moderately correlated with letter fluency scores. Letter fluency scores were weakly correlated with ventricular and thalamic volume. To better understand how imaging findings are related to disease progression, nineteen C9+ subjects and 23 healthy controls were scanned approximately 6 months later. Ventricular volume increased in C9+ patients with FTD and ALS-FTD phenotypes and remained stable in asymptomatic C9+ subjects. We conclude that diffuse atrophy is a common underlying feature of disease associated with C9orf72 mutations across its clinical phenotypes. Ventricular enlargement can be measured over a 6-month time frame, and appears to be faster in patients with cognitive impairment. Published by Elsevier Inc. C1 [Floeter, Mary Kay; Bageac, Devin; Danielian, Laura E.; Braun, Laura E.] NINDS, Motor Neuron Disorders Unit, OCD, NIH, 10 Ctr Dr Room 7-5680, Bethesda, MD 20892 USA. [Traynor, Bryan J.] NIA, Neuromuscular Dis Res Sect LNG, NIH, 35 Convent Dr Room 1A213, Bethesda, MD 20892 USA. [Kwan, Justin Y.] Univ Maryland, Dept Neurol, 110 S Paca St, Baltimore, MD 21201 USA. RP Floeter, MK (reprint author), NINDS, Motor Neuron Disorders Unit, OCD, NIH, 10 Ctr Dr Room 7-5680, Bethesda, MD 20892 USA. EM floeterm@ninds.nih.gov; devin.bageac@nih.gov; danielil@ninds.nih.gov; laura.braun@nih.gov; traynorb@mail.nih.gov; JKwan@som.umaryland.edu FU National Institutes of Health, National Institute of Neurological Disorders and Stroke [Z01 NS003146]; National Institute on Aging [Z01 AG000933] FX The study was supported by the intramural programs of the National Institutes of Health, National Institute of Neurological Disorders and Stroke (Z01 NS003146) and the National Institute on Aging, (Z01 AG000933). We gratefully acknowledge Jennifer Farren, R.N. and Carol Hoffmann for study coordination, the neurologists who referred patients, and the patients and caregivers whose participation was invaluable. This work utilized the computational resources of the NIH HPC Biowulf cluster (http://hpc.nih.gov). Recruitment was made possible in part by ATSDR's National ALS Registry Research Notification Mechanism (http://wwwn.cdc.gov/ALS/ALSClinicalResearch.aspx). NR 64 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 2213-1582 J9 NEUROIMAGE-CLIN JI NeuroImage-Clin. PY 2016 VL 12 BP 1035 EP 1043 DI 10.1016/j.nicl.2016.10.014 PG 9 WC Neuroimaging SC Neurosciences & Neurology GA EF3AI UT WOS:000390196400116 PM 27995069 ER PT J AU Forson, JA Baah-Ennumh, TY Buracom, P Chen, GJ Peng, Z AF Forson, Joseph Ato Baah-Ennumh, Theresa Yaaba Buracom, Ponlapat Chen, Guojin Peng, Zhen TI CAUSES OF CORRUPTION: EVIDENCE FROM SUB-SAHARAN AFRICA SO SOUTH AFRICAN JOURNAL OF ECONOMIC AND MANAGEMENT SCIENCES LA English DT Article DE corruption; sustainable development (SD); institutional quality; sub-Saharan Africa (SSA); governance ID FOREIGN-AID; DEMOCRACY; GROWTH; ACCOUNTABILITY; GOVERNMENT; EDUCATION; FREEDOM; SYSTEMS; TRUST AB This study explores the causes of corruption in 22 countries in sub-Saharan Africa from 1996 to 2013. The sources of corruption are grouped into three main thematic areas - historical roots, contemporary causes and institutional causes to make way for subjective and objective measures. The subjective measures allow for assessment of the effectiveness of anticorruption policies. Using pooled OLS, fixed-effect and instrumental-variable approaches, and focusing on the perceived level of corruption as the dependent variable, we find that ethnic diversity, resource abundance and educational attainment are markedly less associated with corruption. In contrast, wage levels of bureaucrats and anticorruption measures based on government effectiveness and regulatory quality breed substantial corruption. Press freedom is found to be variedly associated with corruption. On the basis of these findings, we recommend that the fight against corruption on the continent needs to be reinvented through qualitative and assertive institutional reforms. Anticorruption policy decisions should focus on existing educational systems as a conduit for intensifying awareness of the devastating effect of corruption on sustainable national development. C1 [Forson, Joseph Ato; Buracom, Ponlapat] NIDA, Grad Sch Publ Adm, 118 M003,Seri Thai Rd, Bangkok 10240, Thailand. [Baah-Ennumh, Theresa Yaaba] Kwame Nkrumah Univ Sci & Technol, Dept Planning, Kumasi, Ghana. [Chen, Guojin] Xiamen Univ, Wang Yanan Inst Studies Econ, Xiamen Shi, Fujian Sheng, Peoples R China. [Peng, Zhen] Guangdong Univ Technol, Sch Management, Guangzhou, Guangdong, Peoples R China. RP Forson, JA (reprint author), NIDA, Grad Sch Publ Adm, 118 M003,Seri Thai Rd, Bangkok 10240, Thailand. EM datoeagle@yahoo.com OI forson, joseph/0000-0002-5997-5713 NR 63 TC 0 Z9 0 U1 2 U2 2 PU UNIV PRETORIA, DEPT ECONOMICS PI PRETORIA PA TUKKIEWERF 1-11, PRETORIA, 0002, SOUTH AFRICA SN 2222-3436 J9 S AFR J ECON MANAG S JI S. Afr. J. Econ. Manag. Sci. PY 2016 VL 19 IS 4 BP 562 EP 578 DI 10.17159/2222-3436/2016/v19n4a7 PG 17 WC Economics; Management SC Business & Economics GA EE5LA UT WOS:000389647800007 ER PT J AU Deng, YP Wang, HW Hamamoto, R Duan, SW Pirooznia, M Bai, YS AF Deng, Youping Wang, Hongwei Hamamoto, Ryuji Duan, Shiwei Pirooznia, Mehdi Bai, Yongsheng TI Functional Genomics, Genetics, and Bioinformatics 2016 SO Biomed Research International LA English DT Article ID BIOMARKERS; DISEASE; CANCER C1 [Deng, Youping] Univ Hawaii, John A Burns Sch Med, Dept Trop Med Med Microbiol & Pharmacol, Bioinformat Core,Off Biostat & Quantitat Hlth Sci, Honolulu, HI 96813 USA. [Wang, Hongwei] Univ Chicago, Dept Med, 5841 S Maryland Ave, Chicago, IL 60637 USA. [Hamamoto, Ryuji] Natl Canc Ctr, Div Mol Modificat & Canc Biol, Tokyo, Japan. [Duan, Shiwei] Ningbo Univ, Sch Med, Ningbo 315211, Zhejiang, Peoples R China. [Pirooznia, Mehdi] NHLBI, Bioinformat & Computat Biol Core Facil, Off Sci Director, NIH, Bethesda, MD 20814 USA. [Bai, Yongsheng] Indiana State Univ, Dept Biol, Terre Haute, IN 47809 USA. RP Deng, YP (reprint author), Univ Hawaii, John A Burns Sch Med, Dept Trop Med Med Microbiol & Pharmacol, Bioinformat Core,Off Biostat & Quantitat Hlth Sci, Honolulu, HI 96813 USA. EM dengy@hawaii.edu OI Bai, Yongsheng/0000-0002-9944-5426 FU NIH [5P30GM114737, P20GM103466] FX The work edition was supported by the Grant NIH 5P30GM114737 and the Grant NIH P20GM103466. NR 16 TC 0 Z9 0 U1 1 U2 1 PU HINDAWI PUBLISHING CORP PI NEW YORK PA 315 MADISON AVE 3RD FLR, STE 3070, NEW YORK, NY 10017 USA SN 2314-6133 EI 2314-6141 J9 BIOMED RES INT JI Biomed Res. Int. PY 2016 AR 2625831 DI 10.1155/2016/2625831 PG 3 WC Biotechnology & Applied Microbiology; Medicine, Research & Experimental SC Biotechnology & Applied Microbiology; Research & Experimental Medicine GA EE1XD UT WOS:000389376200001 ER PT S AU de Herrera, AGS Long, LR Antani, S AF de Herrera, Alba G. Seco Long, L. Rodney Antani, Sameer BE Ascoli, GA Hawrylycz, M Ali, H Khazanchi, D Shi, Y TI Content-Based fMRI Brain Maps Retrieval SO Brain Informatics and Health SE Lecture Notes in Artificial Intelligence LA English DT Proceedings Paper CT International Conference on Brain Informatics and Health (BIH) CY OCT 13-16, 2016 CL Omaha, NE SP Univ Nebraska, Coll Informat Sci & Technol, Web Intelligence Consortium, IEEE Computat Intelligence Soc Task Force Brain Informat DE fMRI retrieval; PICA; Brain activation map ID CLASSIFICATION AB The statistical analysis of functional magnetic resonance imaging (fMRI) is used to extract functional data of cerebral activation during a given experimental task. It allows for assessing changes in cerebral function related to cerebral activities. This methodology has been widely used and a few initiatives aim to develop shared data resources. Searching these data resources for a specific research goal remains a challenging problem. In particular, work is needed to create a global content-based (CB) fMRI retrieval capability. This work presents a CB fMRI retrieval approach based on the brain activation maps extracted using Probabilistic Independent Component Analysis (PICA). We obtained promising results on data from a variety of experiments which highlight the potential of the system as a tool that provides support for finding hidden similarities between brain activation maps. C1 [de Herrera, Alba G. Seco; Long, L. Rodney; Antani, Sameer] Natl Lib Med, Lister Hill Natl Ctr Biomed Commun, Bethesda, MD 20209 USA. RP de Herrera, AGS (reprint author), Natl Lib Med, Lister Hill Natl Ctr Biomed Commun, Bethesda, MD 20209 USA. EM albagarcia@nih.gov; l.long@nih.gov; sameer.antani@nih.gov NR 20 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER-VERLAG BERLIN PI BERLIN PA HEIDELBERGER PLATZ 3, D-14197 BERLIN, GERMANY SN 0302-9743 BN 978-3-319-47103-7; 978-3-319-47102-0 J9 LECT NOTES ARTIF INT PY 2016 VL 9919 BP 173 EP 180 DI 10.1007/978-3-319-47103-7_17 PG 8 WC Computer Science, Artificial Intelligence; Computer Science, Interdisciplinary Applications; Neurosciences SC Computer Science; Neurosciences & Neurology GA BG5HC UT WOS:000389498800017 ER PT J AU Fan, WP Huang, P Chen, XY AF Fan, Wenpei Huang, Peng Chen, Xiaoyuan TI Overcoming the Achilles' heel of photodynamic therapy SO CHEMICAL SOCIETY REVIEWS LA English DT Review ID UP-CONVERSION NANOPARTICLES; MESOPOROUS SILICA NANOPARTICLES; NEAR-INFRARED LIGHT; SINGLET OXYGEN GENERATION; RESONANCE ENERGY-TRANSFER; PHOTOTHERMAL/PHOTODYNAMIC CANCER-THERAPY; INTRANUCLEAR DRUG-DELIVERY; POSSESSING DISULFIDE BOND; IN-VITRO DEMONSTRATION; X-RAY LUMINESCENCE AB Photodynamic therapy (PDT) has been applied to treat a wide range of medical conditions, including wet age-related macular degeneration psoriasis, atherosclerosis, viral infection and malignant cancers. However, the tissue penetration limitation of excitation light hinders the widespread clinical use of PDT. To overcome this "Achilles'heel'', deep PDT, a novel type of phototherapy, has been developed for the efficient treatment of deep-seated diseases. Based on the different excitation sources, including near-infrared (NIR) light, X-ray radiation, and internal self-luminescence, a series of deep PDT techniques have been explored to demonstrate the advantages of deep cancer therapy over conventional PDT excited by ultraviolet-visible (UV-Vis) light. In particular, the featured applications of deep PDT, such as organelle-targeted deep PDT, hypoxic deep PDT and deep PDT-involved multimodal synergistic therapy are discussed. Finally, the future development and potential challenges of deep PDT are also elucidated for clinical translation. It is highly expected that deep PDT will be developed as a versatile, depth/oxygen-independent and minimally invasive strategy for treating a variety of malignant tumours at deep locations. C1 [Fan, Wenpei; Huang, Peng] Shenzhen Univ, Sch Med, Dept Biomed Engn, Guangdong Key Lab Biomed Measurements & Ultrasoun, Shenzhen 518060, Peoples R China. [Fan, Wenpei] Shenzhen Univ, Coll Optoelect Engn, Key Lab Optoelect Devices & Syst, Minist Educ & Guangdong Prov, Shenzhen 518060, Peoples R China. [Fan, Wenpei; Chen, Xiaoyuan] Natl Inst Biomed Imaging & Bioengn, Lab Mol Imaging & Nanomed, NIH, Bethesda, MD 20892 USA. RP Huang, P (reprint author), Shenzhen Univ, Sch Med, Dept Biomed Engn, Guangdong Key Lab Biomed Measurements & Ultrasoun, Shenzhen 518060, Peoples R China.; Chen, XY (reprint author), Natl Inst Biomed Imaging & Bioengn, Lab Mol Imaging & Nanomed, NIH, Bethesda, MD 20892 USA. EM peng.huang@szu.edu.cn; shawn.chen@nih.gov RI Huang, Peng/R-2480-2016 OI Huang, Peng/0000-0003-3651-7813 FU Shenzhen University; National Science Foundation of China [81401465, 51573096, 51602203]; Postdoctoral Science Foundation of China [2016M590808]; Intramural Research Program (IRP) of the NIBIB, NIH FX This project is financially supported by the startup fund from the Shenzhen University, the National Science Foundation of China (81401465, 51573096, 51602203), the Postdoctoral Science Foundation of China (2016M590808), and the Intramural Research Program (IRP) of the NIBIB, NIH. NR 316 TC 2 Z9 2 U1 42 U2 42 PU ROYAL SOC CHEMISTRY PI CAMBRIDGE PA THOMAS GRAHAM HOUSE, SCIENCE PARK, MILTON RD, CAMBRIDGE CB4 0WF, CAMBS, ENGLAND SN 0306-0012 EI 1460-4744 J9 CHEM SOC REV JI Chem. Soc. Rev. PY 2016 VL 45 IS 23 BP 6488 EP 6519 DI 10.1039/c6cs00616g PG 32 WC Chemistry, Multidisciplinary SC Chemistry GA EE1CJ UT WOS:000389318100006 PM 27722560 ER PT J AU Zhou, ZJ Song, JB Nie, LM Chen, XY AF Zhou, Zijian Song, Jibin Nie, Liming Chen, Xiaoyuan TI Reactive oxygen species generating systems meeting challenges of photodynamic cancer therapy SO CHEMICAL SOCIETY REVIEWS LA English DT Review ID UP-CONVERSION NANOPARTICLES; RESONANCE ENERGY-TRANSFER; WALLED CARBON NANOTUBES; NEAR-INFRARED LIGHT; GENETICALLY ENCODED PHOTOSENSITIZER; 2-PHOTON EXCITATION FLUORESCENCE; ACUTE PROMYELOCYTIC LEUKEMIA; METAL-ORGANIC FRAMEWORKS; HYPOXIC TUMOR-CELLS; SINGLET-OXYGEN AB The reactive oxygen species (ROS)-mediated mechanism is the major cause underlying the efficacy of photodynamic therapy (PDT). The PDT procedure is based on the cascade of synergistic effects between light, a photosensitizer (PS) and oxygen, which greatly favors the spatiotemporal control of the treatment. This procedure has also evoked several unresolved challenges at different levels including (i) the limited penetration depth of light, which restricts traditional PDT to superficial tumours; (ii) oxygen reliance does not allow PDT treatment of hypoxic tumours; (iii) light can complicate the phototherapeutic outcomes because of the concurrent heat generation; (iv) specific delivery of PSs to sub-cellular organelles for exerting effective toxicity remains an issue; and (v) side effects from undesirable white-light activation and self-catalysation of traditional PSs. Recent advances in nanotechnology and nanomedicine have provided new opportunities to develop ROS-generating systems through photodynamic or non-photodynamic procedures while tackling the challenges of the current PDT approaches. In this review, we summarize the current status and discuss the possible opportunities for ROS generation for cancer therapy. We hope this review will spur pre-clinical research and clinical practice for ROS-mediated tumour treatments. C1 [Zhou, Zijian; Nie, Liming] Xiamen Univ, Sch Publ Hlth, Ctr Mol Imaging & Translat Med, State Key Lab Mol Vaccinol & Mol Diagnost, Xiamen 361102, Peoples R China. [Zhou, Zijian; Song, Jibin; Chen, Xiaoyuan] Natl Inst Biomed Imaging & Bioengn, Lab Mol Imaging & Nanomed, NIH, Bethesda, MD 20892 USA. RP Nie, LM (reprint author), Xiamen Univ, Sch Publ Hlth, Ctr Mol Imaging & Translat Med, State Key Lab Mol Vaccinol & Mol Diagnost, Xiamen 361102, Peoples R China.; Chen, XY (reprint author), Natl Inst Biomed Imaging & Bioengn, Lab Mol Imaging & Nanomed, NIH, Bethesda, MD 20892 USA. EM nielm@xmu.edu.cn; shawn.chen@nih.gov FU National Basic Research Program of China (863 Program) [2015AA020502]; National Science Foundation of China [81571744, 81301257, 81601489]; Science Foundation of Fujian Province [2014Y2004]; Intramural Research Program (IRP), National Institute of Biomedical Imaging and Bioengineering (NIBIB), National Institutes of Health (NIH) FX This work was supported by National Basic Research Program of China (863 Program 2015AA020502), the National Science Foundation of China (81571744, 81301257, and 81601489), Science Foundation of Fujian Province (No. 2014Y2004), and by the Intramural Research Program (IRP), National Institute of Biomedical Imaging and Bioengineering (NIBIB), National Institutes of Health (NIH). We thank Dr Iqbal Ali for proofreading the manuscript. NR 329 TC 2 Z9 2 U1 91 U2 91 PU ROYAL SOC CHEMISTRY PI CAMBRIDGE PA THOMAS GRAHAM HOUSE, SCIENCE PARK, MILTON RD, CAMBRIDGE CB4 0WF, CAMBS, ENGLAND SN 0306-0012 EI 1460-4744 J9 CHEM SOC REV JI Chem. Soc. Rev. PY 2016 VL 45 IS 23 BP 6597 EP 6626 DI 10.1039/c6cs00271d PG 30 WC Chemistry, Multidisciplinary SC Chemistry GA EE1CJ UT WOS:000389318100009 PM 27722328 ER PT S AU Wang, YO Yao, JH Roth, HR Burns, JE Summers, RM AF Wang, Yinong Yao, Jianhua Roth, Holger R. Burns, Joseph E. Summers, Ronald M. BE Vrtovec, T Yao, J Glocker, B Klinder, T Frangi, A Zheng, G Li, S TI Multi-atlas Segmentation with Joint Label Fusion of Osteoporotic Vertebral Compression Fractures on CT SO Computational Methods and Clinical Applications for Spine Imaging, CSI 2015 SE Lecture Notes in Computer Science LA English DT Proceedings Paper CT 3rd International Workshop and Challenge on Computational Methods and Clinical Applications for Spine Imaging (CSI) CY OCT 05, 2015 CL Munich, GERMANY SP Brainlab AG AB The precise and accurate segmentation of the vertebral column is essential in the diagnosis and treatment of various orthopedic, neurological, and oncological traumas and pathologies. Segmentation is especially challenging in the presence of pathology such as vertebral compression fractures. In this paper, we propose a method to produce segmentations for osteoporotic compression fractured vertebrae by applying a multi-atlas joint label fusion technique for clinical computed tomography (CT) images. A total of 170 thoracic and lumbar vertebrae were evaluated using atlases from five patients with varying degrees of spinal degeneration. In an osteoporotic cohort of bundled atlases, registration provided an average Dice coefficient and mean absolute surface distance of 92.7 +/- 4.5% and 0.32 +/- 0.13 mm for osteoporotic vertebrae, respectively, and 90.9 +/- 3.0% and 0.36 +/- 0.11 mm for compression fractured vertebrae. C1 [Wang, Yinong; Yao, Jianhua; Roth, Holger R.; Summers, Ronald M.] NIH, Ctr Clin, Dept Radiol & Imaging Sci, Imaging Biomarkers & Computer Aided Diag Lab, Bldg 10, Bethesda, MD 20892 USA. [Burns, Joseph E.] Univ Calif Irvine, Sch Med, Dept Radiol Sci, Irvine, CA 92717 USA. RP Yao, JH (reprint author), NIH, Ctr Clin, Dept Radiol & Imaging Sci, Imaging Biomarkers & Computer Aided Diag Lab, Bldg 10, Bethesda, MD 20892 USA. EM yinong.wang@nih.gov; jyao@cc.nih.gov; holger.roth@nih.gov; jburns@uci.edu; rsummers@cc.nih.gov NR 14 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER INT PUBLISHING AG PI CHAM PA GEWERBESTRASSE 11, CHAM, CH-6330, SWITZERLAND SN 0302-9743 BN 978-3-319-41827-8; 978-3-319-41826-1 J9 LECT NOTES COMPUT SC PY 2016 VL 9402 BP 74 EP 84 DI 10.1007/978-3-319-41827-8_7 PG 11 WC Computer Science, Interdisciplinary Applications; Computer Science, Theory & Methods; Radiology, Nuclear Medicine & Medical Imaging SC Computer Science; Radiology, Nuclear Medicine & Medical Imaging GA BG5IF UT WOS:000389504400007 ER PT J AU Alves, VM Capuzzi, SJ Muratov, EN Braga, RC Thornton, TE Fourches, D Strickland, J Kleinstreuer, N Andrade, CH Tropsha, A AF Alves, Vinicius M. Capuzzi, Stephen J. Muratov, Eugene N. Braga, Rodolpho C. Thornton, Thomas E. Fourches, Denis Strickland, Judy Kleinstreuer, Nicole Andrade, Carolina H. Tropsha, Alexander TI QSAR models of human data can enrich or replace LLNA testing for human skin sensitization SO GREEN CHEMISTRY LA English DT Article ID LYMPH-NODE ASSAY; DIVERSE ORGANIC-CHEMICALS; ALLERGIC CONTACT-DERMATITIS; INSULT PATCH TEST; RISK-ASSESSMENT; HAZARD IDENTIFICATION; GREEN CHEMISTRY; APPLICABILITY DOMAIN; CHEMOGENOMICS DATA; MAXIMIZATION TEST AB Skin sensitization is a major environmental and occupational health hazard. Although many chemicals have been evaluated in humans, there have been no efforts to model these data to date. We have compiled, curated, analyzed, and compared the available human and LLNA data. Using these data, we have developed reliable computational models and applied them for the virtual screening of chemical libraries to identify putative skin sensitizers. The overall concordance between murine LLNA and human skin sensitization responses for a set of 135 unique chemicals was low (R = 28-43%), although several chemical classes had high concordance. We have succeeded to develop predictive QSAR models of all available human data with the external correct classification rate of 71%. A consensus model integrating concordant QSAR predictions and LLNA results afforded a higher CCR of 82% but at the expense of the reduced external dataset coverage (52%). We used the developed QSAR models for the virtual screening of the CosIng database and identified 1061 putative skin sensitizers; for seventeen of these compounds, we found published evidence of their skin sensitization effects. Models reported herein provide more accurate alternatives to LLNA testing for human skin sensitization assessment across diverse chemical data. In addition, they can also be used to guide the structural optimization of toxic compounds to reduce their skin sensitization potential. C1 [Alves, Vinicius M.; Capuzzi, Stephen J.; Muratov, Eugene N.; Thornton, Thomas E.; Tropsha, Alexander] Univ N Carolina, UNC Eshelman Sch Pharm, Div Chem Biol & Med Chem, Lab Mol Modeling, Chapel Hill, NC 27599 USA. [Alves, Vinicius M.; Braga, Rodolpho C.; Andrade, Carolina H.] Univ Fed Goias, Lab Mol Modeling & Design, Fac Pharm, BR-74605170 Goiania, Go, Brazil. [Muratov, Eugene N.] Odessa Natl Polytech Univ, Dept Chem Technol, UA-65000 Odessa, Ukraine. [Fourches, Denis] North Carolina State Univ, Bioinformat Res Ctr, Dept Chem, Raleigh, NC 27695 USA. [Strickland, Judy] Integrated Lab Syst Inc, POB 13501, Res Triangle Pk, NC 27709 USA. [Kleinstreuer, Nicole] Natl Inst Environm Hlth Sci, Res Triangle Pk, NC 27709 USA. [Tropsha, Alexander] Kazan Fed Univ, AM Butlerov Inst Chem, 18 Kremlyovskaya Str, Kazan 420008, Russia. RP Tropsha, A (reprint author), Univ N Carolina, UNC Eshelman Sch Pharm, Div Chem Biol & Med Chem, Lab Mol Modeling, Chapel Hill, NC 27599 USA.; Tropsha, A (reprint author), Kazan Fed Univ, AM Butlerov Inst Chem, 18 Kremlyovskaya Str, Kazan 420008, Russia. EM alex_tropsha@unc.edu FU NIH [GM096967]; FAPEG [201310267001095]; CNPq [400760/2014-2]; Russian Scientific Foundation [14-43-00024]; Russian Government Program for Competitive Growth of the Kazan Federal University; NIEHS, NIH [HHSN273201500010C] FX This study was supported in part by NIH (GM096967), FAPEG (grant 201310267001095), CNPq (grant 400760/2014-2), Russian Scientific Foundation (Agreement No. 14-43-00024 from October 1, 2014) and Russian Government Program for Competitive Growth of the Kazan Federal University. J. S. is supported by the NIEHS, NIH under Contract No. HHSN273201500010C to ILS in support of NICEATM. ILS staff provide technical support for NICEATM, but do not represent NIEHS, NTP, or the official positions of any federal agency. This article may be the work product of an employee or a group of employees of the NIEHS, NIH, or other organizations; however, the statements, opinions, or conclusions contained therein do not necessarily represent the statements, opinions, or conclusions of NIEHS, NIH, the United States government, or other organizations. The use of commercial product names is for comparative purposes only and does not constitute endorsement by any of the authors, organizations, or agencies. The authors express sincere gratitude to Drs Vladimir Poroikov, Dmitri Filimonov, and Alexey Zakharov for providing the GUSAR software. NR 115 TC 1 Z9 1 U1 1 U2 1 PU ROYAL SOC CHEMISTRY PI CAMBRIDGE PA THOMAS GRAHAM HOUSE, SCIENCE PARK, MILTON RD, CAMBRIDGE CB4 0WF, CAMBS, ENGLAND SN 1463-9262 EI 1463-9270 J9 GREEN CHEM JI Green Chem. PY 2016 VL 18 IS 24 BP 6501 EP 6515 DI 10.1039/c6gc01836j PG 15 WC Chemistry, Multidisciplinary; GREEN & SUSTAINABLE SCIENCE & TECHNOLOGY SC Chemistry; Science & Technology - Other Topics GA EE1LA UT WOS:000389341800011 ER PT J AU Cuburu, N Schiller, JT AF Cuburu, Nicolas Schiller, John T. TI Moving forward with human papillomavirus immunotherapies SO HUMAN VACCINES & IMMUNOTHERAPEUTICS LA English DT Article DE Human papillomavirus; cancer; immunotherapy; therapeutic vaccines; mucosal immunity ID CERVICAL INTRAEPITHELIAL NEOPLASIA; RANDOMIZED-CONTROLLED-TRIAL; CD8(+) T-CELLS; MHC CLASS-I; THERAPEUTIC VACCINATION; PROTECTIVE IMMUNITY; FUSION PROTEIN; HPV INFECTION; GENITAL-TRACT; CIN3 PATIENTS AB Persistent human papillomavirus (HPV) is the primary etiologic agent of cervical cancer and causes a significant number of vulvar, penile, anal and oropharyngeal cancers. The development of highly effective HPV therapeutic vaccines is a reasonable goal given the recent advances in basic and applied immunology. A number of vaccine strategies designed to induce systemic T cell responses have been tested in clinical trials against high grade cervical or vulvar high grade neoplasia and cancers, but with limited success. In line with the emerging trend to focus more on the epithelial context of HPV infection and premalignant disease, it might be advantageous to develop vaccination strategies that promote trafficking of HPV-specific T cells into lesions and overcome the local immunosuppressive environment. The development of more biologically relevant animal models would improve the preclinical evaluation of therapeutic vaccine candidates. Finally, persistent infection and low grade lesions may prove to be easier targets for therapeutic vaccines, and these vaccines would likely be commercially viable in high income countries and valuable components in screen and treat programs in low resource settings. C1 [Cuburu, Nicolas; Schiller, John T.] NCI, Cellular Oncol Lab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. RP Cuburu, N (reprint author), 37 Convent Dr,Rm 4106, Bethesda, MD 20892 USA. EM cuburun@mail.nih.gov NR 58 TC 0 Z9 0 U1 1 U2 1 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 530 WALNUT STREET, STE 850, PHILADELPHIA, PA 19106 USA SN 2164-5515 EI 2164-554X J9 HUM VACC IMMUNOTHER JI Human Vaccines Immunother. PY 2016 VL 12 IS 11 BP 2875 EP 2880 DI 10.1080/21645515.2016.1199302 PG 6 WC Biotechnology & Applied Microbiology; Immunology SC Biotechnology & Applied Microbiology; Immunology GA ED3GF UT WOS:000388736900032 PM 27388123 ER PT S AU Altman, BM Rasch, EK AF Altman, Barbara M. Rasch, Elizabeth K. BE Altman, BM TI Purpose of an International Comparable Census Disability Measure SO International Measurement of Disability: Purpose, Method and Application: The Work of the Washington Group SE Social Indicators Research Series LA English DT Article; Book Chapter C1 [Altman, Barbara M.] Natl Ctr Hlth Stat, Washington Grp Secretariat, Hyattsville, MD 20782 USA. [Rasch, Elizabeth K.] NIH, Dept Rehabil Med, Epidemiol & Biostat Sect, Bethesda, MD 20892 USA. RP Altman, BM (reprint author), Natl Ctr Hlth Stat, Washington Grp Secretariat, Hyattsville, MD 20782 USA. EM b.altman@verizon.net NR 8 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER INT PUBLISHING AG PI CHAM PA GEWERBESTRASSE 11, CHAM, CH-6330, SWITZERLAND SN 1387-6570 BN 978-3-319-28498-9; 978-3-319-28496-5 J9 SOC INDIC RES SER PY 2016 VL 61 BP 55 EP 68 DI 10.1007/978-3-319-28498-9_4 D2 10.1007/978-3-319-28498-9 PG 14 WC Health Policy & Services; Social Issues SC Health Care Sciences & Services; Social Issues GA BG4RP UT WOS:000389058800005 ER PT J AU Yeo, D Huynh, N Beutler, JA Baldwin, GS He, H Nikfarjam, M AF Yeo, Dannel Nhi Huynh Beutler, John A. Baldwin, Graham S. He, Hong Nikfarjam, Mehrdad TI Glaucarubinone Combined with Gemcitabine Improves Pancreatic Cancer Survival in an Immunocompetent Orthotopic Murine Model SO JOURNAL OF INVESTIGATIVE SURGERY LA English DT Article DE glaucarubinone; gemcitabine; pancreatic cancer; survival ID INDUCIBLE FACTOR 1-ALPHA; P21-ACTIVATED KINASES; BETA-CATENIN; PATHWAY; GROWTH; ADENOCARCINOMA; COMBINATION; ACTIVATION; MALARIA; GENES AB Background: Pancreatic cancer continues to have a poor survival rate with an urgent need for improved treatments. Glaucarubinone, a natural product first isolated from the seeds of the tree Simarouba glauca, has recently been recognized as having anti-cancer properties that may be particularly applicable to pancreatic cancer. Methods: The effect of glaucarubinone on the growth and migration of murine pancreatic cancer cells was assessed by H-3-thymidine incorporation assay. The survival impact of glaucarubinone alone and in combination with gemcitabine chemotherapy was assessed using an immunocompetent orthotopic murine model of pancreatic cancer. Results: Glaucarubinone inhibited the growth of the murine pancreatic cancer cell lines LM-P and PAN02. Treatment with either glaucarubinone or gemcitabine reduced proliferation in vitro and the combination was synergistic. The combination treatment improved survival two-fold compared to gemcitabine treatment alone (p = 0.046) in PAN02 cells. Conclusions: The synergistic inhibition by glaucarubinone and gemcitabine observed in vitro and the improved survival in vivo suggest that glaucarubinone may be a useful adjunct to current chemotherapy regimens. C1 [Yeo, Dannel; Nhi Huynh; Baldwin, Graham S.; He, Hong; Nikfarjam, Mehrdad] Univ Melbourne, Dept Surg, Austin Hlth, Melbourne, Vic, Australia. [Beutler, John A.] NCI, Mol Targets Lab, Frederick, MD 21701 USA. RP Nikfarjam, M (reprint author), Austin Hlth, Univ Dept Surg, Studley Rd, Melbourne, Vic 3084, Australia. EM m.nikfarjam@unimelb.edu.au FU Austin Hospital Medical Research Foundation; Sir Edward Dunlop Foundation; National Health of Medical Research Council (NHMRC) of Australia [1020983, 508908]; Australian Rotary Health (The Ian Loxton Pancreatic Cancer Research PhD Scholarship); Pancare Foundation FX This work was supported by grants from the Austin Hospital Medical Research Foundation, the Sir Edward Dunlop Foundation, and the National Health of Medical Research Council (NHMRC) of Australia (1020983, GSB; 508908, HH). Dannel Yeo is supported by Australian Rotary Health (The Ian Loxton Pancreatic Cancer Research PhD Scholarship). We also acknowledge the funding support of the Pancare Foundation (www.pancare.org.au) provided to develop novel therapies for the treatment of pancreatic cancer. NR 27 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 0894-1939 EI 1521-0553 J9 J INVEST SURG JI J. Invest. Surg. PY 2016 VL 29 IS 6 BP 366 EP 372 DI 10.3109/08941939.2016.1160167 PG 7 WC Surgery SC Surgery GA ED3JI UT WOS:000388745000007 PM 27027695 ER PT J AU Hu, GW McQuiston, T Bernard, A Park, YD Qiu, J Vural, A Zhang, NN Waterman, SR Blewett, NH Myers, TG Kehrl, JH Uzel, G Klionsky, DJ Williamson, PR AF Hu, Guowu McQuiston, Travis Bernard, Amelie Park, Yoon-Dong Qiu, Jin Vural, Ali Zhang, Nannan Waterman, Scott R. Blewett, Nathan H. Myers, Timothy G. Kehrl, John H. Uzel, Gulbu Klionsky, Daniel J. Williamson, Peter R. TI Tor-dependent post-transcriptional regulation of autophagy: Implications for cancer therapeutics SO Molecular & Cellular Oncology LA English DT Article DE Autoimmunity; autophagy; oncology; pharmacology; phosphorylation; Tor; tumor immunology ID DEGRADATION; NEOFORMANS; VIRULENCE AB Paradoxically, both anticancer immunosurveillance and tumor progression have been associated with intact autophagy, which is regulated by the target of rapamycin (Tor1). Here, we describe the potential impact on the design of cancer therapeutics of a newly described highly conserved post-transcriptional mechanism whereby Tor regulates autophagy. C1 [Hu, Guowu; McQuiston, Travis; Park, Yoon-Dong; Qiu, Jin; Zhang, Nannan; Waterman, Scott R.; Uzel, Gulbu; Williamson, Peter R.] NIAID, Lab Clin Infect Dis, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA. [Bernard, Amelie; Klionsky, Daniel J.] Univ Michigan, Inst Life Sci, Ann Arbor, MI 48109 USA. [Vural, Ali; Kehrl, John H.] NIAID, Immunoregulat Lab, NIH, Bldg 10, Bethesda, MD 20892 USA. [Blewett, Nathan H.] NICHHD, Intramural Res Program Genom Differentiat, NIH, Bethesda, MD 20892 USA. [Myers, Timothy G.] NIAID, Genom Technol Sect, Res Technol Branch, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA. RP Williamson, PR (reprint author), NIAID, Lab Clin Infect Dis, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA. EM williamsonpr@mail.nih.gov FU Intramural Research Program of the NIH; NIAID; NICHD; National Institutes of Health [GM053396] FX This work was funded, in part, by the Intramural Research Program of the NIH, NIAID, and NICHD and by National Institutes of Health grant GM053396 (to D.J.K.). NR 10 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 2372-3556 EI 2372-3548 J9 MOL CELL ONCOL JI MOL. CELL ONCOL. PY 2016 VL 3 IS 5 DI 10.1080/23723556.2015.1078923 PG 3 WC Oncology SC Oncology GA ED9HT UT WOS:000389181500002 ER PT J AU Deng, WW Mao, L Yu, GT Bu, LL Ma, SR Liu, B Gutkind, JS Kulkarni, AB Zhang, WF Sun, ZJ AF Deng, Wei-Wei Mao, Liang Yu, Guang-Tao Bu, Lin-Lin Ma, Si-Rui Liu, Bing Gutkind, J. Silvio Kulkarni, Ashok B. Zhang, Wen-Feng Sun, Zhi-Jun TI LAG-3 confers poor prognosis and its blockade reshapes antitumor response in head and neck squamous cell carcinoma SO OncoImmunology LA English DT Article DE Antitumor response; head and neck squamous cell carcinoma; immunosuppressive cells; LAG-3; prognosis ID REGULATORY T-CELLS; IMMUNE CHECKPOINTS; COLORECTAL-CANCER; SUPPRESSOR-CELLS; OVARIAN-CANCER; MYELOID CELLS; MOUSE MODEL; ACTIVATION; GENE; PD-1 AB Immunotherapy with immune checkpoint molecule-specific monoclonal antibody have obtained encouraging results from preclinical studies and clinical trials, which promoted us to explore whether this kind of immunotherapy could be applicable to head and neck squamous cell carcinoma (HNSCC). Lymphocyte activation gene-3 (LAG-3) is an immune checkpoint control protein that negatively regulates T cells and immune response. Here, using the human tissue samples, we report these findings that LAG-3 is overexpressed on tumor-infiltrating lymphocytes (TILs; p < 0.001) and its overexpression correlates with the high pathological grades, lager tumor size and positive lymph node status in human primary HNSCC. Survival analysis identifies LAG-3 as a prognostic factor independent of tumor size and pathological grades for primary HNSCC patients with negative lymph node status ( p = 0.014). Study in immunocompetent genetically defined HNSCC mouse model reports that LAG-3 is upregulated on CD4(+) T cells, CD8(+) T cells and CD4(+)Foxp3(+) regulatory T cells (Tregs). In vivo study, administration of LAG-3-specific antibody retards tumor growth in a way associated with enhanced systemic antitumor response by potentiating the antitumor response of CD8(+) T cells and decreasing the population of immunosuppressive cells. Taken together, our results offer a preclinical proof supporting the immunomodulatory effects of LAG-3 and suggest a potential therapeutic target of immunotherapy for HNSCC. C1 [Deng, Wei-Wei; Mao, Liang; Yu, Guang-Tao; Bu, Lin-Lin; Ma, Si-Rui; Liu, Bing; Zhang, Wen-Feng; Sun, Zhi-Jun] Wuhan Univ, State Key Lab Breeding Base Basic Sci Stomatol Hu, Wuhan, Peoples R China. [Deng, Wei-Wei; Mao, Liang; Yu, Guang-Tao; Bu, Lin-Lin; Ma, Si-Rui; Liu, Bing; Zhang, Wen-Feng; Sun, Zhi-Jun] Wuhan Univ, Key Lab Oral Biomed, Minist Educ, Sch & Hosp Stomatol, Wuhan, Peoples R China. [Liu, Bing; Zhang, Wen-Feng; Sun, Zhi-Jun] Wuhan Univ, Sch & Hosp Stomatol, Dept Oral Maxillofacial Head Neck Oncol, Wuhan, Peoples R China. [Gutkind, J. Silvio] Univ Calif San Diego, Dept Pharmacol, San Diego, CA 92103 USA. [Kulkarni, Ashok B.; Sun, Zhi-Jun] Natl Inst Dent & Craniofacial Res, Funct Genom Sect, Lab Cell & Dev Biol, NIH, Bethesda, MD USA. RP Sun, ZJ (reprint author), Wuhan Univ, Sch & Hosp Stomatol, 237 Luoyu Rd, Wuhan 430079, Peoples R China. EM sunzj@whu.edu.cn FU National Natural Science Foundation of China [81272963, 81472528, 81672668, 81272964, 81472529]; Division of Intramural Research, NIDCR, NIH, USA; program for New Century Excellent Talents in University, Ministry of Education of China [NCET-13-0439] FX This work was supported by National Natural Science Foundation of China 81272963, 81472528, 81672668 (Z.J. Sun), 81272964, 81472529 (W.F. Zhang), and the Division of Intramural Research, NIDCR, NIH, USA (A.B. Kulkarni). Z.J. Sun was supported by program for New Century Excellent Talents in University (NCET-13-0439), Ministry of Education of China. NR 54 TC 0 Z9 0 U1 3 U2 3 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 530 WALNUT STREET, STE 850, PHILADELPHIA, PA 19106 USA SN 2162-402X J9 ONCOIMMUNOLOGY JI OncoImmunology PY 2016 VL 5 IS 11 AR e1239005 DI 10.1080/2162402X.2016.1239005 PG 14 WC Oncology; Immunology SC Oncology; Immunology GA ED8UG UT WOS:000389145800025 PM 27999760 ER PT J AU Tomita, Y Lee, MJ Lee, S Tomita, S Chumsri, S Cruickshank, S Ordentlich, P Trepel, JB AF Tomita, Yusuke Lee, Min-Jung Lee, Sunmin Tomita, Saori Chumsri, Saranya Cruickshank, Scott Ordentlich, Peter Trepel, Jane B. TI The interplay of epigenetic therapy and immunity in locally recurrent or metastatic estrogen receptor-positive breast cancer: Correlative analysis of ENCORE 301, a randomized, placebo-controlled phase II trial of exemestane with or without entinostat SO OncoImmunology LA English DT Article DE Breast cancer; entinostat; exemestane; histone deacetylase inhibitors; HLA-DR; immune checkpoint receptor; immune subsets; monocyte; myeloid-derived suppressor cell; regulatory T cell ID HISTONE DEACETYLASE INHIBITORS; THYMIC EPITHELIAL TUMORS; RENAL-CELL CARCINOMA; REGULATORY T-CELLS; MHC CLASS-I; SUPPRESSOR-CELLS; CHECKPOINT BLOCKADE; HDAC INHIBITORS; BLADDER-CANCER; OPEN-LABEL AB Entinostat, a class I-selective histone deacetylase inhibitor, has shown promising activity in ENCORE 301, a randomized, placebo-controlled, phase II trial of exemestane with or without entinostat in women with locally recurrent or metastatic estrogen receptor-positive breast cancer progressing on a nonsteroidal aromatase inhibitor. ENCORE 301 showed an 8.3-mo improvement in median overall survival among patients who received entinostat. We investigated the impact of entinostat on immune subsets with CD40, HLA-DR, and immune checkpoint receptor expression analyses in 34 patient blood samples from ENCORE 301. We found that entinostat significantly decreased granulocytic and monocytic MDSCs at cycle 1 day 15. MDSC CD40 was significantly downregulated by entinostat. A significant increase in HLA-DR expression on CD14(+) monocytes by entinostat was observed. Entinostat did not impact T-cell subsets or T-cell immune checkpoint receptor expression. Our findings suggest that a significant interplay between this epigenetic regimen and host immune homeostatic mechanisms may impact therapeutic outcome. C1 [Tomita, Yusuke; Lee, Min-Jung; Lee, Sunmin; Tomita, Saori; Trepel, Jane B.] NCI, Dev Therapeut Branch, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. [Chumsri, Saranya] Mayo Clin, Jacksonville, FL 32224 USA. [Cruickshank, Scott; Ordentlich, Peter] Syndax Pharmaceut Inc, Waltham, MA USA. RP Trepel, JB (reprint author), NCI, Dev Therapeut Branch, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. EM trepel@helix.nih.gov FU Intramural Research Program, Center for Cancer Research, National Cancer Institute, National Institutes of Health; Syndax Pharmaceuticals FX This work was supported by the Intramural Research Program, Center for Cancer Research, National Cancer Institute, National Institutes of Health and by research funding and clinical trial support from Syndax Pharmaceuticals. NR 50 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 2162-402X J9 ONCOIMMUNOLOGY JI OncoImmunology PY 2016 VL 5 IS 11 AR e1219008 DI 10.1080/2162402X.2016.1219008 PG 12 WC Oncology; Immunology SC Oncology; Immunology GA ED8UG UT WOS:000389145800004 PM 27999738 ER PT J AU Lee, CT Boeshore, KL Wu, C Becker, KG Errico, SL Mash, DC Freed, WJ AF Lee, Chun-Ting Boeshore, Kristen L. Wu, Chun Becker, Kevin G. Errico, Stacie L. Mash, Deborah C. Freed, William J. TI Cocaine promotes primary human astrocyte proliferation via JNK-dependent up-regulation of cyclin A2 SO RESTORATIVE NEUROLOGY AND NEUROSCIENCE LA English DT Article DE Astrocytes; cocaine; reactive astrogliosis; addiction; JNK; cyclin A ID CELL-PROLIFERATION; NUCLEUS-ACCUMBENS; STRUCTURAL PLASTICITY; SIGNALING PATHWAYS; DENDRITIC SPINES; REACTIVE GLIOSIS; GENE ONTOLOGY; IN-VIVO; EXPRESSION; ACTIVATION AB Purpose: Astrocytes perform a plethora of important functions in the central nervous system (CNS) and are involved in cocaine-evoked synaptic plasticity. Previously, we showed that while cocaine decreased cyclin A2 expression in primary human neural progenitor cells, it increased cyclin A2 expression in human astrocytes. Since cyclin A2 is an essential regulator of the cell cycle, the aim of the present study is to clarify the effect of cocaine on proliferation of human astrocytes and elucidate the underlying molecular mechanisms. Methods: Primary human astrocytes were treated with either 1, 10, or 100 mu M cocaine for 48 hr, and cell proliferation was measured using the CyQUANT cell proliferation assay. To elucidate the molecular mechanisms through which cocaine affects the proliferation of astrocytes, we analyzed gene expression profiles in cocaine-treated primary human astrocytes using a human focused cDNA array. Gene ontology/pathway enrichment analysis, STRING protein-protein interaction analysis, RT-qPCR, and western blotting were used to identify signal transduction pathways that are involved in cocaine-induced astrocyte dysfunction. Results: Cocaine at 10 and 100 mu M significantly increased human astrocyte proliferation. Gene expression profiling revealed the JNK MAP kinase pathway as a driver of cell proliferation affected by cocaine in human astrocytes. Further experiments showed that cocaine-induced JNK activation induced up-regulation of cyclin A2, leading to enhanced proliferation of human astrocytes. Conclusion: Cocaine-induced abnormal increases in the number of astrocytes may cause disruption in neuron-glia signaling and contribute to synaptic impairment in the CNS. Understanding the mechanisms of cocaine's effects on human astrocytes may help to reveal the involvement of glial cells in addictive behaviors. C1 [Lee, Chun-Ting; Errico, Stacie L.; Freed, William J.] NIDA, Sect Dev & Plast, Cellular Neurobiol Res Branch, Intramural Res Program,NIH, Baltimore, MD USA. [Lee, Chun-Ting; Mash, Deborah C.] Univ Miami, Miller Sch Med, Dept Neurol, Miami, FL 33136 USA. [Boeshore, Kristen L.; Freed, William J.] Lebanon Valley Coll, Dept Biol, Annville, PA USA. [Wu, Chun; Mash, Deborah C.] Univ Miami, Miller Sch Med, Dept Mol & Cellular Pharmacol, Miami, FL 33136 USA. [Becker, Kevin G.] NIA, Gene Express & Genom Unit, Res Resources Branch, IRP,NIH, Baltimore, MD 21224 USA. RP Lee, CT (reprint author), US FDA, Ctr Biol Evaluat & Res, Bldg 52,Rm 1121,10903 New Hampshire Ave, Silver Spring, MD 20993 USA. EM Chun-Ting.Lee@fda.hhs.gov FU Intramural Research Programs of the National Institute on Drug Abuse; National Institute on Aging FX This work was supported by the Intramural Research Programs of the National Institute on Drug Abuse and the National Institute on Aging. NR 77 TC 0 Z9 0 U1 3 U2 3 PU IOS PRESS PI AMSTERDAM PA NIEUWE HEMWEG 6B, 1013 BG AMSTERDAM, NETHERLANDS SN 0922-6028 EI 1878-3627 J9 RESTOR NEUROL NEUROS JI Restor. Neurol. Neurosci. PY 2016 VL 34 IS 6 BP 965 EP 976 DI 10.3233/RNN-160676 PG 12 WC Neurosciences SC Neurosciences & Neurology GA EE0DG UT WOS:000389243100008 PM 27834787 ER PT J AU Kim, SY Assawachananont, J AF Kim, Soo-Young Assawachananont, Juthaporn TI A New Method to Visualize the Intact Subretina From Retinal Pigment Epithelium to Retinal Tissue in Whole Mount of Pigmented Mouse Eyes SO TRANSLATIONAL VISION SCIENCE & TECHNOLOGY LA English DT Article DE RPE/retina whole mount; melanin bleaching; subretina ID CLARITY AB Purpose: The subretinal layer between apical retinal pigment epithelium (RPE) and the apices of the photoreceptor outer segments is important to aging and degenerative pathogenesis, but current protocols do not provide intact horizontal images of this retinal space. Thus, an RPE/retina whole mount staining protocol was developed to observe integral subretinal regions. Methods: RPE/retina whole mounts were stained instead of separated retina or RPE wholemounts. Hydrogen peroxide (H2O2) treatment was applied in different conditions of concentration, time, and temperature for the bleaching of RPE and choroidal melanocyte pigmentation in the pigmented RPE/retina whole mounts before antibody staining. Results: An RPE/retina whole mount staining protocol provided better morphology of the photoreceptor outer segment than current retina whole mount. For the pigmented eyes, 10% H2O2 pretreatment effectively bleached melanin at 55 degrees C less than 2 hours, or at 4 degrees C within 7 days, without significant effect on immunolabeling efficacy of most antibodies tested. Actually, 55 degrees C bleaching improved immunolabeling intensities compared to the nonbleaching control. This melanin bleaching RPE/retina protocol was applied further to observe macrophage/microglia extending from the sclera to outer plexiform layer in the CX3CR1+/GFP retina. Conclusions: The pigment bleaching RPE/retina whole mount allowed integral horizontal imaging between choroid to photoreceptor layers, which could not be accomplished with existing methods of separated retina or RPE whole mount. Under these procedures, antigenicity of most antibodies also was well preserved. Translational Relevance: This efficient protocol provides a tool to observe an integral view of subretinal structures including macrophage/microglia and transplanted cells, and further allows study of the interrelationship between the choroid and photoreceptor in models of aging, disease, and retinal degeneration. C1 [Kim, Soo-Young; Assawachananont, Juthaporn] NEI, Neurobiol Neurodegenerat & Repair Lab, NIH, Bethesda, MD 20892 USA. RP Kim, SY (reprint author), Johns Hopkins Sch Med, Ctr Nanomed, Dept Ophthalmol, Baltimore, MD 21231 USA. EM skim370@jh.edu FU Intramural Research Program of the National Eye Institute FX Supported by the Intramural Research Program of the National Eye Institute. NR 8 TC 0 Z9 0 U1 0 U2 0 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI ROCKVILLE PA 12300 TWINBROOK PARKWAY, ROCKVILLE, MD 20852-1606 USA SN 2164-2591 J9 TRANSL VIS SCI TECHN JI Transl. Vis. Sci. Technol. PD JAN PY 2016 VL 5 IS 1 AR 6 DI 10.1167/tvst.5.1.6 PG 8 WC Ophthalmology SC Ophthalmology GA ED2IZ UT WOS:000388668800006 ER PT S AU Iakovidis, DK Dimas, G Ciuti, G Bianchi, F Karargyris, A Koulaouzidis, A Toth, E AF Iakovidis, Dimitris K. Dimas, George Ciuti, Gastone Bianchi, Federico Karargyris, Alexandros Koulaouzidis, Anastasios Toth, Ervin GP IEEE Instrumentat & Measurement Soc TI Robotic Validation of Visual Odometry for Wireless Capsule Endoscopy SO 2016 IEEE INTERNATIONAL CONFERENCE ON IMAGING SYSTEMS AND TECHNIQUES (IST) SE IEEE International Conference on Imaging Systems and Techniques LA English DT Proceedings Paper CT IEEE International Conference on Imaging Systems and Techniques (IST) / IEEE International School on Imaging CY OCT 04-06, 2016 CL Chania, GREECE SP IEEE, IEEE Instrumentat & Measurement Soc DE wireless capsule endoscopy; visual odometry; camera calibration; test benches for measurements ID DIAGNOSIS; MODEL AB Wireless capsule endoscopy (WCE) is the prime diagnostic modality for the small-bowel. It consists in a swallowable color camera that enables the visual detection and assessment of abnormalities, without patient discomfort. The localization of the capsule is currently performed in the 3D abdominal space using radiofrequency (RF) triangulation. However, this approach does not provide sufficient information for the localization of the capsule, and therefore for the localization of the detected abnormalities, within the gastrointestinal (GI) lumen. To cope with this problem, we have recently proposed a method for visual tracking of the capsule endoscope (CE). It is based solely on visual features extracted from the captured images during the journey of the CE in the GI tract, enabling therefore visual odometry. Due to lack of ex-vivo or in-vivo ground truth data, the feasibility of that method was assessed using relative measurements in an image-based simulation experiment. In this paper, we make one step forward towards the assessment of the absolute localization capabilities of visual odometry using a calibrated in-vitro experimental setup. The obtained results validate the feasibility of the proposed approach, highlight the difficulty of this complex problem, and reveal the challenges ahead. C1 [Iakovidis, Dimitris K.; Dimas, George] Univ Thessaly, Dept Comp Sci & Biomed Informat, Lamia, Greece. [Ciuti, Gastone; Bianchi, Federico] St Anna Sch Adv Studies, BioRobot Inst, Pisa, Italy. [Karargyris, Alexandros] NIH, US Natl Lib Med, Bldg 10, Bethesda, MD 20892 USA. [Koulaouzidis, Anastasios] Royal Infirm Edinburgh NHS Trust, Endoscopy Unit, Edinburgh, Midlothian, Scotland. [Toth, Ervin] Lund Univ, Skane Univ Hosp, Dept Gastroenterol, Malmo, Sweden. RP Iakovidis, DK (reprint author), Univ Thessaly, Dept Comp Sci & Biomed Informat, Lamia, Greece. NR 23 TC 0 Z9 0 U1 0 U2 0 PU IEEE PI NEW YORK PA 345 E 47TH ST, NEW YORK, NY 10017 USA SN 2471-6162 BN 978-1-5090-1817-8 J9 IEEE CONF IMAGING SY PY 2016 BP 83 EP 87 PG 5 WC Computer Science, Artificial Intelligence; Engineering, Electrical & Electronic; Imaging Science & Photographic Technology SC Computer Science; Engineering; Imaging Science & Photographic Technology GA BG4GC UT WOS:000388735200014 ER PT S AU Kong, LJ Tang, JY Cui, M AF Kong, Lingjie Tang, Jianyong Cui, Meng BE Bifano, TG Kubby, J Gigan, S TI Volumetric imaging of fast biological dynamics in deep tissue via wavefront engineering SO ADAPTIVE OPTICS AND WAVEFRONT CONTROL FOR BIOLOGICAL SYSTEMS II SE Proceedings of SPIE LA English DT Proceedings Paper CT Conference on Adaptive Optics and Wavefront Control for Biological Systems II CY FEB 13-15, 2016 CL San Francisco, CA SP SPIE DE volumetric imaging; adaptive optics; biomedical optics; multiphoton microscopy; biological dynamics; three-dimensional microscopy; two-photon microscopy ID ADAPTIVE COMPENSATION TECHNIQUE; NEURONAL-ACTIVITY; FLUORESCENCE MICROSCOPY; OPTICAL MICROSCOPY; MOUSE-BRAIN; LIGHT; SYSTEM AB To reveal fast biological dynamics in deep tissue, we combine two wavefront engineering methods that were developed in our laboratory, namely optical phase-locked ultrasound lens (OPLUL) based volumetric imaging and iterative multiphoton adaptive compensation technique (IMPACT). OPLUL is used to generate oscillating defocusing wavefront for fast axial scanning, and IMPACT is used to compensate the wavefront distortions for deep tissue imaging. We show its promising applications in neuroscience and immunology. C1 [Kong, Lingjie; Cui, Meng] Purdue Univ, Sch Elect & Comp Engn, W Lafayette, IN 47907 USA. [Tang, Jianyong] NIAID, Lab Syst Biol, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA. [Cui, Meng] Purdue Univ, Dept Biol Sci, W Lafayette, IN 47907 USA. [Cui, Meng] Purdue Univ, Integrated Imaging Cluster, W Lafayette, IN 47907 USA. [Cui, Meng] Purdue Univ, Bindley Biosci Ctr, W Lafayette, IN 47907 USA. RP Kong, LJ (reprint author), Purdue Univ, Sch Elect & Comp Engn, W Lafayette, IN 47907 USA. EM kong52@purdue.edu RI kong, lingjie/G-5822-2012 OI kong, lingjie/0000-0003-1974-3245 NR 31 TC 0 Z9 0 U1 2 U2 2 PU SPIE-INT SOC OPTICAL ENGINEERING PI BELLINGHAM PA 1000 20TH ST, PO BOX 10, BELLINGHAM, WA 98227-0010 USA SN 0277-786X BN 978-1-62841-951-1 J9 PROC SPIE PY 2016 VL 9717 AR UNSP 97170J DI 10.1117/12.2211417 PG 7 WC Microscopy; Optics; Imaging Science & Photographic Technology SC Microscopy; Optics; Imaging Science & Photographic Technology GA BG4TI UT WOS:000389085900016 ER PT S AU Eldridge, MAG Chandra, S Richmond, BJ AF Eldridge, Mark A. G. Chandra, Samarth Richmond, Barry J. BE Wang, R Pan, X TI Is Visual Processing in Primates Strictly Hierarchical? SO ADVANCES IN COGNITIVE NEURODYNAMICS (V) SE Advances in Cognitive Neurodynamics LA English DT Proceedings Paper CT 5th International Conference on Cognitive Neurodynamics (ICCN) CY JUN 03-07, 2015 CL Sanya, PEOPLES R CHINA SP East China Univ Sci & Technol, Inst Cognit Neurodynam, Chinese Soc Theoret & Appl Mech, Brain Engn Soc Korea, Tamagawa Univ, Brain Sci Ctr, KAIST, Brain Sci Res Ctr, Int Neural Network Soc, Japan Soc Neural Network, Shanghai Soc Nonlinear Sci, Natl Nat Sci Fdn China ID MONKEY; CORTEX AB Over the past four decades, the dominant view of visual processing in primates is that the complexity of feature analysis increases as information flows from primary visual cortex rostrally through regions of the temporal lobe, into area TE, where whole complex objects are represented. This view is consistent with observations that TE neurons are selective for complex objects such as hands and faces. We test a major prediction: bilateral removal of area TE will damage high-level visual object categorization, such as distinguishing cats from dogs. After removal of TE, this type of categorical classification is only mildly impaired in old-world monkeys. However, when the images are degraded by a small amount of visual noise, the monkeys are virtually unable to correctly classify morphs of cats versus dogs. This raises the possibility that area TE makes it possible to identify partially obscured objects, that is, it is critical for pattern completion. C1 [Eldridge, Mark A. G.; Chandra, Samarth; Richmond, Barry J.] NIMH, Neuropsychol Lab, NIH, Bldg 49,Rm 1B80, Bethesda, MD 20892 USA. RP Richmond, BJ (reprint author), NIMH, Neuropsychol Lab, NIH, Bldg 49,Rm 1B80, Bethesda, MD 20892 USA. EM bjr@ln.nimh.nih.gov NR 8 TC 0 Z9 0 U1 2 U2 2 PU SPRINGER-VERLAG SINGAPORE PTE LTD PI SINGAPORE PA SINGAPORE, SINGAPORE SN 2213-3569 BN 978-981-10-0207-6; 978-981-10-0205-2 J9 ADV COGN NEURODYN PY 2016 BP 9 EP 12 DI 10.1007/978-981-10-0207-6_2 PG 4 WC Neurosciences SC Neurosciences & Neurology GA BG3JN UT WOS:000387956200002 ER PT J AU Lejbman, N Olivera, A Heinzelmann, M Feng, R Yun, S Kim, HS Gill, J AF Lejbman, Natasha Olivera, Anlys Heinzelmann, Morgan Feng, Rebekah Yun, Sijung Kim, Hyung-Suk Gill, Jessica TI Active duty service members who sustain a traumatic brain injury have chronically elevated peripheral concentrations of A40 and lower ratios of A42/40 SO BRAIN INJURY LA English DT Article DE Traumatic brain injury; military; amyloid; tauopathies ID AMYLOID PRECURSOR PROTEIN; ALZHEIMERS-DISEASE; HEAD-INJURY; NEUROLOGICAL STATUS; MILITARY PERSONNEL; BETA DYNAMICS; ENCEPHALOPATHY; ASSOCIATION; POPULATION; DEPOSITION AB Primary objective: Excessive accumulation of amyloid beta (A) and tau have been observed in older individuals with chronic neurological symptoms related to a traumatic brain injury (TBI), yet little is known about the possible role of A in younger active duty service members following a TBI. The purpose of the study was to determine if A 40 or 42 related to sustaining a TBI or to chronic neurological symptoms in a young cohort of military personnel.Research design: This was a cross-sectional study of active duty service members who reported sustaining a TBI and provided self-report of neurological and psychological symptoms and provided blood.Methods and procedures: An ultrasensitive single-molecule enzyme-linked immunosorbent assay was used to compare concentrations of A in active duty service members with (TBI+; n = 53) and without (TBI-; n = 18) a history of TBI. Self-report and medical history were used to measure TBI occurrence and approximate the number of total TBIs and the severity of TBIs sustained during deployment.Main outcomes and results: This study reports that TBI is associated with higher concentrations of A40 (F-1,F-68 = 6.948, p = 0.009) and a lower ratio of A42/A40 (F-1,F-62 = 5.671, p = 0.020). These differences remained significant after controlling for co-morbid symptoms of post-traumatic stress disorder and depression.Conclusions: These findings suggest that alterations in A relate to TBIs and may contribute to chronic neurological symptoms. C1 [Lejbman, Natasha; Olivera, Anlys; Heinzelmann, Morgan; Feng, Rebekah; Yun, Sijung; Kim, Hyung-Suk; Gill, Jessica] NIH, NINR, Bldg 10, Bethesda, MD 20892 USA. [Yun, Sijung] LLC, Yotta Biomed, Bethesda, MD USA. RP Gill, J (reprint author), 1 Cloister Court,Rm 256, Bethesda, MD 20814 USA. EM gillj@mail.nih.gov FU Center for Neuroscience and Regenerative Medicine [60855]; National Institutes of Nursing Research FX This study was funded, in part, by the Center for Neuroscience and Regenerative Medicine (Grant 60855). This study was funded by the intramural research program of the National Institutes of Nursing Research. The authors report no conflicts of interest. The opinions and assertions in this manuscript are those of the authors and do not necessarily represent those of the Department of the Army, Department of Defense, US Government, or the Center for Neuroscience and Regenerative Medicine. NR 37 TC 0 Z9 0 U1 1 U2 1 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 530 WALNUT STREET, STE 850, PHILADELPHIA, PA 19106 USA SN 0269-9052 EI 1362-301X J9 BRAIN INJURY JI Brain Inj. PY 2016 VL 30 IS 12 BP 1436 EP 1441 DI 10.1080/02699052.2016.1219054 PG 6 WC Neurosciences; Rehabilitation SC Neurosciences & Neurology; Rehabilitation GA ED1IO UT WOS:000388599100005 PM 27834544 ER PT J AU Li, GH Henderson, L Nath, A AF Li, Guan-Han Henderson, Lisa Nath, Avindra TI Astrocytes as an HIV Reservoir: Mechanism of HIV Infection SO CURRENT HIV RESEARCH LA English DT Review DE Astrocyte; CXCR4; endocytosis; HIV; latency; reservoir ID HUMAN-IMMUNODEFICIENCY-VIRUS; CENTRAL-NERVOUS-SYSTEM; HUMAN FETAL ASTROCYTES; NECROSIS-FACTOR-ALPHA; CHEMOKINE RECEPTOR CCR5; SRC-ASSOCIATED PROTEIN; IN-SITU HYBRIDIZATION; HUMAN GLIAL-CELLS; TYPE-1 INFECTION; CEREBROSPINAL-FLUID AB If we have any hope of achieving a cure for HIV infection, close attention to the cell types capable of getting infected with HIV is necessary. Of these cell types, astrocytes are the most ideal cell type for the formation of such a reservoir. These are long-lived cells with a very low turnover rate and are found in the brain and the gastrointestinal tract. Although astrocytes are evidently resistant to infection of cell-free HIV in vitro, these cells are efficiently infected via cell-tocell contact by which immature HIV virions bud off lymphocytes and have the ability to directly bind to CXCR4, triggering the process of fusion in the absence of CD4. In this review, we closely examine the evidence for HIV infection of astrocytes in the brain and the mechanisms for viral entry and regulation in this cell type, and discuss an approach for controlling this viral reservoir. C1 [Li, Guan-Han; Henderson, Lisa; Nath, Avindra] NINDS, Sect Infect Nervous Syst, NIH, 10 Ctr Dr,7C120, Bethesda, MD 20814 USA. RP Li, GH (reprint author), NINDS, Sect Infect Nervous Syst, NIH, 10 Ctr Dr,7C120, Bethesda, MD 20814 USA. EM guanhan.li@nih.gov NR 141 TC 0 Z9 0 U1 0 U2 0 PU BENTHAM SCIENCE PUBL LTD PI SHARJAH PA EXECUTIVE STE Y-2, PO BOX 7917, SAIF ZONE, 1200 BR SHARJAH, U ARAB EMIRATES SN 1570-162X EI 1873-4251 J9 CURR HIV RES JI Curr. HIV Res. PY 2016 VL 14 IS 5 BP 373 EP 381 DI 10.2174/1570162X14666161006121455 PG 9 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA ED6SE UT WOS:000388985500002 PM 27719663 ER PT J AU Joseph, J Colosi, DA Rao, VR AF Joseph, Jeymohan Colosi, Deborah A. Rao, Vasudev R. TI HIV-1 Induced CNS Dysfunction: Current Overview and Research Priorities SO CURRENT HIV RESEARCH LA English DT Review DE NeuroAIDS; HIV; dementia; HIV associated neurocognitive disorders; NIMH; research priorities; HAND; CNS reservoirs; HIV cure; neuronal dysfunction; AIDS ID HUMAN-IMMUNODEFICIENCY-VIRUS; CENTRAL-NERVOUS-SYSTEM; BLOOD-BRAIN-BARRIER; NEUROCOGNITIVE DISORDERS; ANTIRETROVIRAL THERAPY; CEREBROSPINAL-FLUID; COGNITIVE IMPAIRMENT; AIDS DEMENTIA; EXTRACELLULAR VESICLES; INCREASED FREQUENCY AB Background: Over the past three decades, the clinical presentation of HIV infection of the Central Nervous System (CNS) has evolved. Prior to wide spread use of effective antiretroviral therapy (ART), more than a third of infected individuals exhibited a range of neurocognitive and motor deficits that frequently progressed to severe dementia and paralysis. However, the use of ART has significantly decreased the prevalence of severe forms of HIV-1 associated neurocognitive disorders (HAND). Studies of neurocognitive dysfunction have reported variable prevalence, ranging from 21% to 77.6%, defined primarily by mild to moderate neurocognitive impairment. HIV-associated chronic inflammation and associated neurotoxicity of long term ART, as well as the aging of the HIV-infected population, likely influence the pathogenesis of HAND. Despite significant research efforts directed towards a better understanding of the mechanisms underlying HIV neuropathogenesis, definitive causal pathophysiology of HAND and thus effective prevention or treatment remain elusive. Furthermore, HIV therapeutic research now includes efforts to effect a cure, by eliminating or silencing HIV within infected cells, which must include efforts to target the latently infected cells within the CNS. Conclusion: Prevention and treatment of the neurological complications of HIV, and eradication of persistent virus from the CNS compartment are major priorities for the HIV-CNS research. Here we give an overview of the progress of research on HIV-CNS disease, define new challenges and research areas, and highlight domestic and global priorities. C1 [Joseph, Jeymohan; Colosi, Deborah A.; Rao, Vasudev R.] NIMH, HIV Neuropathogenesis Genet & Therapeut Branch, Div AIDS Res, Bethesda, MD 20892 USA. RP Joseph, J (reprint author), NIMH, HIV Neuropathogenesis Genet & Therapeut Branch, Div AIDS Res, Bethesda, MD 20892 USA. EM jjeymoha@mail.nih.gov NR 124 TC 1 Z9 1 U1 0 U2 0 PU BENTHAM SCIENCE PUBL LTD PI SHARJAH PA EXECUTIVE STE Y-2, PO BOX 7917, SAIF ZONE, 1200 BR SHARJAH, U ARAB EMIRATES SN 1570-162X EI 1873-4251 J9 CURR HIV RES JI Curr. HIV Res. PY 2016 VL 14 IS 5 BP 389 EP 399 DI 10.2174/1570162X14666160324124940 PG 11 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA ED6SE UT WOS:000388985500004 PM 27009096 ER PT J AU Mashimo, M Moss, J AF Mashimo, Masato Moss, Joel TI Functional Role of ADP-Ribosyl-Acceptor Hydrolase 3 in poly(ADP-Ribose) Polymerase-1 Response to Oxidative Stress SO CURRENT PROTEIN & PEPTIDE SCIENCE LA English DT Review DE Poly(ADP-ribose); Poly(ADP-ribose) polymerase 1; ADP-ribose-acceptor hydrolase 3; Parthanatos; Poly(ADP-ribose) glycohydrolase; Apoptosis-inducing factor ID APOPTOSIS-INDUCING FACTOR; CELL-DEATH; DNA-DAMAGE; RIBOSYLARGININE HYDROLASES; MITOCHONDRIAL MATRIX; TURKEY ERYTHROCYTES; PARG ACTIVITY; IN-VIVO; GLYCOHYDROLASE; IDENTIFICATION AB Poly-ADP-ribosylation has been proposed to be a reversible protein modification, participating in diverse cellular functions including DNA repair, chromatin remodeling, genetic stability, mitosis, and cell death. Poly-ADP-ribosylation is initiated by the transfer of the ADP-ribose moiety of NAD(+) primarily to the carboxyl groups of glutamate and aspartate and amino group of lysine residues in target proteins, followed by elongation of poly(ADP-ribose) (PAR) chains via alpha-O-glycosidicc (C-1 ''-C-2') ribose-ribose bonds. PAR consists of polymers of ADP-ribose (up to 200 units) with branching via alpha-O-glycosidic (C-1"'-C-2 '') ribose-ribose bonds. Further, the pyrophosphate group of each ADP-ribose has two negative charges. Therefore, in proteins modified by PAR, a complex structure with negative charges may lead to dynamic changes of functions. PAR formation is catalyzed by poly(ADP-ribose) polymerases (PARPs) and terminated by several types of enzymes with PAR-degrading activities; poly(ADP-ribose) glycohydrolase (PARG), ADP-ribosylacceptor hydrolase (ARH) 3, ARH1, and macrodomain-containing proteins. PARG has been thought to be primarily responsible for PAR degradation. In 2006, ARH3 was cloned and identified as another type of PAR-degrading protein. Although PAR-degrading activity of ARH3 is less than that of PARG, different mechanisms of PAR recognition and the cellular localization of ARH3 appear to be responsible for unique cellular roles of ARH3 involving PAR. In the present review, we focused on our findings regarding structure, biological properties, and cellular functions of ARH3. In addition, we describe the current knowledge of poly-ADP-ribosylation and cell death pathways regulated PARP1, PARG, and ARH3. C1 [Mashimo, Masato] Doshisha Womens Coll Liberal Arts, Fac Pharmaceut Sci, Dept Pharmacol, Kyotanabe, Kyoto 6100395, Japan. [Moss, Joel] NHLBI, Cardiovasc & Pulm Branch, NIH, Bethesda, MD 20892 USA. RP Mashimo, M (reprint author), NIH, Rm 6D05,Bldg 10,MSC 1590, Bethesda, MD 20892 USA. EM mossj@nhlbi.nih.gov FU Intramural Research Program, National Institutes of Health, National Heart, Lung, and Blood Institute; Ministry of Education, Science, Sports and Culture of Japan [15K18871] FX This study was supported by the Intramural Research Program, National Institutes of Health, National Heart, Lung, and Blood Institute and a Grant-in-Aid for Scientific Research (15K18871) from the Ministry of Education, Science, Sports and Culture of Japan. NR 78 TC 0 Z9 0 U1 0 U2 0 PU BENTHAM SCIENCE PUBL LTD PI SHARJAH PA EXECUTIVE STE Y-2, PO BOX 7917, SAIF ZONE, 1200 BR SHARJAH, U ARAB EMIRATES SN 1389-2037 EI 1875-5550 J9 CURR PROTEIN PEPT SC JI Curr. Protein Pept. Sci. PY 2016 VL 17 IS 7 BP 633 EP 640 DI 10.2174/1389203717666160419144603 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA ED1AN UT WOS:000388576000002 PM 27090906 ER PT S AU Pluta, RM Bacher, J Skopets, B Hoffmann, V AF Pluta, Ryszard M. Bacher, John Skopets, Boris Hoffmann, Victoria BE Janowski, M TI A Nonhuman Primate Model of Delayed Cerebral Vasospasm After Aneurismal Subarachnoid Hemorrhage SO EXPERIMENTAL NEUROSURGERY IN ANIMAL MODELS SE Neuromethods LA English DT Article; Book Chapter DE Animal modeling; Human disease; Stroke research; Nonprimate model ID NITRIC-OXIDE METABOLITES; CEREBROSPINAL-FLUID; DOUBLE-BLIND; BLOOD-FLOW; RECEPTOR ANTAGONIST; ANEURYSM-TRIAL; SPINAL-FLUID; BRAIN-INJURY; CLAZOSENTAN; ISCHEMIA AB Animal modeling of human disease has a long history but remains controversial especially when using a sensitive species. Despite these controversies, in a stroke research, a nonprimate model has been recognized as a most successful and useful for developing new treatments. Among stroke models, a nonhuman primate model of delayed cerebral vasospasm after subarachnoid blood clot placement has a very unique position as it revealed important pathomechanisms and led to development of several crucial clinical trials. In 1989, we adopted this model to study pathophysiology and develop a treatment against delayed cerebral vasospasm after intracranial aneurysm rupture (aSAH). In this chapter, we presented detailed descriptions of the animal treatment according to the National Institutes of Health guidance, techniques of anesthesia, cerebral arteriography, suboccipital puncture for cerebrospinal fluid collection, a surgical clot placement along the middle cerebral artery as well as postoperative care, euthanasia, and autopsy. Moreover, to accommodate the recent clinical findings, strongly suggesting a limited role of delayed cerebral vasospasm on the outcome of aSAH, we proposed a modification of the model, which addressed some mechanisms of ultra and early damage to the brain evoked by an intracranial aneurysm rupture. C1 [Pluta, Ryszard M.] NINDS, Surg Neurol Branch, NIH, Bldg 36,Rm 4D04, Bethesda, MD 20892 USA. [Pluta, Ryszard M.] JAMA, Chicago, IL 60611 USA. [Bacher, John; Skopets, Boris; Hoffmann, Victoria] NIH, Div Vet Resources, Off Res Serv, Bldg 10, Bethesda, MD 20892 USA. RP Pluta, RM (reprint author), NINDS, Surg Neurol Branch, NIH, Bldg 36,Rm 4D04, Bethesda, MD 20892 USA.; Pluta, RM (reprint author), JAMA, Chicago, IL 60611 USA. NR 61 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013, UNITED STATES SN 0893-2336 BN 978-1-4939-3730-1; 978-1-4939-3728-8 J9 NEUROMETHODS JI Neuromethods PY 2016 VL 116 BP 227 EP 250 DI 10.1007/978-1-4939-3730-1_16 D2 10.1007/978-1-4939-3730-1 PG 24 WC Clinical Neurology; Surgery SC Neurosciences & Neurology; Surgery GA BG4LP UT WOS:000388975500018 ER PT B AU Meaburn, KJ Burman, B Misteli, T AF Meaburn, Karen J. Burman, Bharat Misteli, Tom BE BazettJones, DP Dellaire, G TI Spatial Genome Organization and Disease SO FUNCTIONAL NUCLEUS LA English DT Article; Book Chapter DE Genome organization; Chromosome territories; Nuclear architecture; Spatial positioning; Gene positioning; Disease; Cancer; Translocations; Chromatin structure ID NUCLEAR LAMINA INTERACTIONS; GILFORD-PROGERIA-SYNDROME; DOUBLE-STRAND BREAKS; RECURRENT CHROMOSOMAL TRANSLOCATIONS; GENE DENSITY; LIVING CELLS; DNA-DAMAGE; INTERPHASE CHROMOSOMES; DOMAIN ORGANIZATION; SEQUENCING REVEALS AB The nucleus is a complex organelle that performs a wide array of critical functions. Within the nucleus the genome is highly organized. Individual chromosomes form discrete chromosome territories. The organization of the genome is correlated with function, for example gene expression. Each chromosome and gene has a preferential spatial location, which can vary by cell type, differentiation stage and during disease. Active and inactive chromatin tends to be spatially separated both within the 3D nuclear space and within a chromosome territory. The molecular mechanisms that determine genome organization are currently poorly understood. However, it is known that the proximity of gene loci can contribute to translocation partner choice. The recent development of a plethora of new molecular techniques and imaging strategies, combined with fluorescent in situ hybridization, is being applied to both normal and diseased cells. Such studies will bring us closer to understanding the implications of genome organization and the molecules and mechanisms that determine it. C1 [Meaburn, Karen J.; Burman, Bharat; Misteli, Tom] NCI, NIH, Bethesda, MD 20892 USA. [Burman, Bharat] Tufts Univ, Sackler Sch Biomed Sci, Program Cell Mol & Dev Biol, Boston, MA 02111 USA. RP Meaburn, KJ; Misteli, T (reprint author), NCI, NIH, Bethesda, MD 20892 USA. EM meaburnk@mail.nih.gov; burmanb@mail.nih.gov; mistelit@mail.nih.gov NR 128 TC 0 Z9 0 U1 1 U2 1 PU SPRINGER INT PUBLISHING AG PI CHAM PA GEWERBESTRASSE 11, CHAM, CH-6330, SWITZERLAND BN 978-3-319-38882-3; 978-3-319-38880-9 PY 2016 BP 101 EP 125 DI 10.1007/978-3-319-38882-3_5 D2 10.1007/978-3-319-38882-3 PG 25 WC Biochemistry & Molecular Biology; Cell Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Cell Biology; Genetics & Heredity GA BG4HC UT WOS:000388824400005 ER PT S AU Yasgar, A Jadhav, A Simeonov, A Coussens, NP AF Yasgar, Adam Jadhav, Ajit Simeonov, Anton Coussens, Nathan P. BE Janzen, WP TI AlphaScreen-Based Assays: Ultra-High-Throughput Screening for Small-Molecule Inhibitors of Challenging Enzymes and Protein-Protein Interactions SO HIGH THROUGHPUT SCREENING: METHODS AND PROTOCOLS, 3RD EDITION SE Methods in Molecular Biology LA English DT Article; Book Chapter DE AlphaLISA; AlphaScreen; High-throughput screening; Assay; ELISA; HTS; Enzyme; Protein-protein interaction ID HUMAN SALIVA; IMMUNOASSAY; IDENTIFICATION; VALIDATION AB AlphaScreen technology has been routinely utilized in high-throughput screening assays to quantify analyte accumulation or depletion, bimolecular interactions, and post-translational modifications. The high signal-to-background, dynamic range, and sensitivity associated with AlphaScreens as well as the homogenous assay format and reagent stability make the technology particularly well suited for high-throughput screening applications. Here, we describe the development of AlphaScreen assays to identify small-molecule inhibitors of enzymes and protein-protein interactions using the highly miniaturized 1536-well format. The subsequent implementation of counter assays to identify false-positive compounds is also discussed. C1 [Yasgar, Adam; Jadhav, Ajit; Simeonov, Anton] NIH, NCATS, Rockville, MD 20892 USA. [Coussens, Nathan P.] NIH, Div Preclin Innovat, NCATS, Rockville, MD USA. RP Yasgar, A (reprint author), NIH, NCATS, Rockville, MD 20892 USA. NR 24 TC 1 Z9 1 U1 2 U2 2 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013, UNITED STATES SN 1064-3745 BN 978-1-4939-3673-1; 978-1-4939-3671-7 J9 METHODS MOL BIOL JI Methods Mol. Biol. PY 2016 VL 1439 BP 77 EP 98 DI 10.1007/978-1-4939-3673-1_5 D2 10.1007/978-1-4939-3673-1 PG 22 WC Biochemical Research Methods; Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA BG4LS UT WOS:000388978300006 PM 27316989 ER PT S AU Fogel, AI Martin, SE Hasson, SA AF Fogel, Adam I. Martin, Scott E. Hasson, Samuel A. BE Janzen, WP TI Application of Imaging-Based Assays in Microplate Formats for High-Content Screening SO HIGH THROUGHPUT SCREENING: METHODS AND PROTOCOLS, 3RD EDITION SE Methods in Molecular Biology LA English DT Article; Book Chapter DE High-content screening; High-content analysis; Automated microscopy; RNAi; siRNA; Functional genomics; Imaging assay; Assay development; Image analysis ID SMALL-MOLECULE INHIBITORS; SCALE RNAI SCREENS; ACTIVATE PARKIN; PINK1; UBIQUITIN; DISEASE; ZEBRAFISH; MUTATIONS; AUTOPHAGY; ETIOLOGY AB The use of multiparametric microscopy-based screens with automated analysis has enabled the large-scale study of biological phenomena that are currently not measurable by any other method. Collectively referred to as high-content screening (HCS), or high-content analysis (HCA), these methods rely on an expanding array of imaging hardware and software automation. Coupled with an ever-growing amount of diverse chemical matter and functional genomic tools, HCS has helped open the door to a new frontier of understanding cell biology through phenotype-driven screening. With the ability to interrogate biology on a cell-by-cell basis in highly parallel microplate-based platforms, the utility of HCS continues to grow as advancements are made in acquisition speed, model system complexity, data management, and analysis systems. This chapter uses an example of screening for genetic factors regulating mitochondrial quality control to exemplify the practical considerations in developing and executing high-content campaigns. C1 [Fogel, Adam I.] Biogen, Cambridge, MA 02142 USA. [Martin, Scott E.] Genentech Inc, Dept Discovery Oncol, San Francisco, CA 94080 USA. [Hasson, Samuel A.] NIH, Natl Ctr Adv Translat Sci, Rockville, MD USA. [Hasson, Samuel A.] Pfizer Inc, Cambridge, MA USA. RP Fogel, AI (reprint author), Biogen, Cambridge, MA 02142 USA. NR 33 TC 1 Z9 1 U1 0 U2 1 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013, UNITED STATES SN 1064-3745 BN 978-1-4939-3673-1; 978-1-4939-3671-7 J9 METHODS MOL BIOL JI Methods Mol. Biol. PY 2016 VL 1439 BP 273 EP 304 DI 10.1007/978-1-4939-3673-1_18 D2 10.1007/978-1-4939-3673-1 PG 32 WC Biochemical Research Methods; Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA BG4LS UT WOS:000388978300019 PM 27317002 ER PT S AU Rahnasto-Rilla, M Lahtela-Kakkonen, M Moaddel, R AF Rahnasto-Rilla, Minna Lahtela-Kakkonen, Maija Moaddel, Ruin BE Sarkar, S TI Sirtuin 6 (SIRT6) Activity Assays SO HISTONE DEACETYLASES: METHODS AND PROTOCOLS SE Methods in Molecular Biology LA English DT Article; Book Chapter DE Deacetylation assays; Activation assays; Inhibition assays; Bioaffinity chromatography; In silico screening ID MAMMALIAN SIRTUINS; INHIBITORS; PROTEIN; DEACETYLASE; MODULATORS; PEPTIDES; MICE AB SIRT6 has been shown to possess weak deacetylation, mono-ADP-ribosyltransferase activity, and deacylation activity in vitro. SIRT6 selectively deacetylates H3K9Ac and H3K56Ac. Several SIRT6 assays have been developed including HPLC assays, fluorogenic assays, FRET, magnetic beads, in silico, and bioaffinity chromatography assays. Herein, we describe detailed protocols for the HPLC based activity/inhibition assays, magnetic beads deacetylation assays, bioaffinity chromatographic assays as well as fluorogenic and in silico assays. C1 [Rahnasto-Rilla, Minna; Moaddel, Ruin] NIA, Bioanalyt & Drug Dev Unit, NIH, Baltimore, MD 21224 USA. [Rahnasto-Rilla, Minna; Lahtela-Kakkonen, Maija] Univ Eastern Finland, Sch Pharm, Kuopio, Finland. RP Rahnasto-Rilla, M (reprint author), NIA, Bioanalyt & Drug Dev Unit, NIH, Baltimore, MD 21224 USA.; Rahnasto-Rilla, M (reprint author), Univ Eastern Finland, Sch Pharm, Kuopio, Finland. FU Intramural NIH HHS [Z99 AG999999, ZIA AG000295-14] NR 17 TC 0 Z9 0 U1 0 U2 2 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013, UNITED STATES SN 1064-3745 BN 978-1-4939-3667-0; 978-1-4939-3665-6 J9 METHODS MOL BIOL JI Methods Mol. Biol. PY 2016 VL 1436 BP 259 EP 269 DI 10.1007/978-1-4939-3667-0_17 D2 10.1007/978-1-4939-3667-0 PG 11 WC Biochemical Research Methods; Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA BG4LT UT WOS:000388979200018 PM 27246220 ER PT S AU Malide, D AF Malide, Daniela BE Bai, M TI In Vivo Cell Tracking Using Two-Photon Microscopy SO IN VIVO FLUORESCENCE IMAGING: METHODS AND PROTOCOLS SE Methods in Molecular Biology LA English DT Article; Book Chapter DE Fluorescent proteins; Multiphoton microscopy; Adipose tissue; Lymph node; Cell tracking; Second harmonic generation; Third harmonic generation ID RED FLUORESCENT PROTEINS; BONE-MARROW FAILURE; MOUSE MODEL; INFUSION; STRATEGIES; TISSUES; STEM AB Recently we have explored and developed approaches imaging using confocal/two-photon microscopy, which enables simultaneous high-resolution assessment of specifically fluorescently marked cells in conjunction with structural components of the tissues visualized via harmonic generated signals. This approach uses commercially available confocal and two-photon laser microscope and automated user-interactive image analysis methods based on commercially available software packages allowing easy implementation in usual microscopy facilities. C1 [Malide, Daniela] NHLBI, Light Microscopy Core Facil, NIH, Bldg 10, Bethesda, MD 20892 USA. RP Malide, D (reprint author), NHLBI, Light Microscopy Core Facil, NIH, Bldg 10, Bethesda, MD 20892 USA. NR 17 TC 1 Z9 1 U1 0 U2 1 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013, UNITED STATES SN 1064-3745 BN 978-1-4939-3721-9; 978-1-4939-3719-6 J9 METHODS MOL BIOL JI Methods Mol. Biol. PY 2016 VL 1444 BP 109 EP 122 DI 10.1007/978-1-4939-3721-9_11 D2 10.1007/978-1-4939-3721-9 PG 14 WC Biochemical Research Methods; Radiology, Nuclear Medicine & Medical Imaging SC Biochemistry & Molecular Biology; Radiology, Nuclear Medicine & Medical Imaging GA BG4LR UT WOS:000388977600012 PM 27283422 ER PT J AU Sung, H Sabourin, JA Sorant, AJM Wilson, AF AF Sung, Heejong Sabourin, Jeremy A. Sorant, Alexa J. M. Wilson, Alexander F. TI The effect of different sets of critical values on type I error rates in tiled regression for genome-wide association studies SO INTERNATIONAL JOURNAL OF DATA MINING AND BIOINFORMATICS LA English DT Article DE multicollinearity; linkage disequilibrium; test of association; GWAS AB The effects of different sets of critical values on type I error rates in tiled regression were investigated using genome-wide association data from the Trinity Student Study. 200 simulated null traits from the standard normal distribution were analysed using four different sets of critical values for stepwise regression within tiled regression. We observed that (1) the multicollinearity among SNPs considered and the aggregate type I error rates decreased through three levels of tiled regression; (2) the region-specific type I error rates were slightly lower than the 'nominal' critical values at the tile level; and (3) the critical value at the tile level is between the two aggregate type I error rates defined under two different assumptions about the number of tests (the number of SNPs and the number of tiles). The choice of critical value at each stage of tiled regression affects the overall type I error rate. C1 [Sung, Heejong; Sabourin, Jeremy A.; Sorant, Alexa J. M.; Wilson, Alexander F.] NHGRI, Genometr Sect, Computat & Stat Genom Branch, NIH, 333 Cassell Dr,Suite 1200, Baltimore, MD 21224 USA. RP Wilson, AF (reprint author), NHGRI, Genometr Sect, Computat & Stat Genom Branch, NIH, 333 Cassell Dr,Suite 1200, Baltimore, MD 21224 USA. EM sunghe@mail.nih.gov; sabourinja@mail.nih.gov; ajms@mail.nih.gov; afw@mail.nih.gov FU Intramural Research Program of the National Human Genome Research Institute, National Institutes of Health FX This project was supported in part by the Intramural Research Program of the National Human Genome Research Institute, National Institutes of Health. We thank Lawrence C. Brody, James L. Mills and Anne M. Molloy for providing the Trinity Student Study data. Heejong Sung and Jeremy A. Sabourin contributed equally to this work. NR 10 TC 0 Z9 0 U1 0 U2 0 PU INDERSCIENCE ENTERPRISES LTD PI GENEVA PA WORLD TRADE CENTER BLDG, 29 ROUTE DE PRE-BOIS, CASE POSTALE 856, CH-1215 GENEVA, SWITZERLAND SN 1748-5673 EI 1748-5681 J9 INT J DATA MIN BIOIN JI Int. J. Data Min. Bioinform. PY 2016 VL 16 IS 2 BP 111 EP 120 DI 10.1504/IJDMB.2016.10000871 PG 10 WC Mathematical & Computational Biology SC Mathematical & Computational Biology GA ED3HD UT WOS:000388739300002 ER PT J AU Abola, MV Prasad, V AF Abola, Matthew V. Prasad, Vinay TI The Use of Superlatives in Cancer Research SO JAMA ONCOLOGY LA English DT Letter C1 [Abola, Matthew V.] Case Western Reserve Univ, Sch Med, Cleveland, OH USA. [Prasad, Vinay] NCI, Med Oncol Serv, NIH, Bethesda, MD 20892 USA. [Prasad, Vinay] Oregon Hlth & Sci Univ, Knight Canc Inst, Div Hematol & Med Oncol, 3181 SW Sam Jackson Pk Rd, Portland, OR 97239 USA. RP Prasad, V (reprint author), Oregon Hlth & Sci Univ, Knight Canc Inst, Div Hematol & Med Oncol, 3181 SW Sam Jackson Pk Rd, Portland, OR 97239 USA. EM prasad@ohsu.edu NR 4 TC 6 Z9 6 U1 0 U2 2 PU AMER MEDICAL ASSOC PI CHICAGO PA 330 N WABASH AVE, STE 39300, CHICAGO, IL 60611-5885 USA SN 2374-2445 J9 JAMA ONCOL JI JAMA Oncol. PD JAN PY 2016 VL 2 IS 1 BP 139 EP 141 DI 10.1001/jamaoncol.2015.3931 PG 4 WC Oncology SC Oncology GA DW5JE UT WOS:000383679300032 PM 26512913 ER PT J AU Freedman, DM Pfeiffer, RM AF Freedman, D. Michal Pfeiffer, Ruth M. TI Factors in Association Between Parkinson Disease and Risk of Cancer in Taiwan SO JAMA ONCOLOGY LA English DT Letter C1 [Freedman, D. Michal; Pfeiffer, Ruth M.] NCI, Div Canc Epidemiol & Genet, 9609 Med Ctr Dr, Rockville, MD 20850 USA. RP Freedman, DM (reprint author), NCI, Div Canc Epidemiol & Genet, 9609 Med Ctr Dr, Rockville, MD 20850 USA. EM freedmam@mail.nih.gov NR 3 TC 2 Z9 2 U1 0 U2 0 PU AMER MEDICAL ASSOC PI CHICAGO PA 330 N WABASH AVE, STE 39300, CHICAGO, IL 60611-5885 USA SN 2374-2445 J9 JAMA ONCOL JI JAMA Oncol. PD JAN PY 2016 VL 2 IS 1 BP 144 EP 145 PG 3 WC Oncology SC Oncology GA DW5JE UT WOS:000383679300039 PM 26767558 ER PT J AU Liu, AY Yue, LQ AF Liu, Aiyi Yue, Lilly Q. TI A conversation with Dr. Greg Campbell SO JOURNAL OF BIOPHARMACEUTICAL STATISTICS LA English DT Editorial Material C1 [Liu, Aiyi] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, NIH, Biostat & Bioinformat Branch, Div Intramural Populat Hlth Res, Bethesda, MD USA. [Yue, Lilly Q.] US FDA, Div Biostat, Ctr Devices & Radiol Hlth, 10903 New Hampshire, Silver Spring, MD 20993 USA. RP Yue, LQ (reprint author), US FDA, Div Biostat, Ctr Devices & Radiol Hlth, 10903 New Hampshire, Silver Spring, MD 20993 USA. EM lilly.yue@fda.hhs.gov OI Liu, Aiyi/0000-0002-6618-5082 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 1054-3406 EI 1520-5711 J9 J BIOPHARM STAT JI J. Biopharm. Stat. PY 2016 VL 26 IS 6 SI SI BP 1007 EP 1019 DI 10.1080/10543406.2016.1226331 PG 13 WC Pharmacology & Pharmacy; Statistics & Probability SC Pharmacology & Pharmacy; Mathematics GA ED1HS UT WOS:000388596600001 PM 27548092 ER PT J AU Collins, J Albert, PS AF Collins, John Albert, Paul S. TI Estimating diagnostic accuracy without a gold standard: A continued controversy SO JOURNAL OF BIOPHARMACEUTICAL STATISTICS LA English DT Article DE Accuracy without gold standard; diagnostic accuracy; latent class model ID LATENT CLASS ANALYSIS; TEST PERFORMANCE; CLASS MODELS; TESTS; ERROR AB There is a wide body of literature in biostatistics and epidemiology literature about estimating diagnostic accuracy, such as sensitivity and specificity of a binary test, without a gold standard. This methodology is very attractive since obtaining gold standard information is impossible, difficult, or very expensive in some situations. Although there are many proponents of these approaches, there have also been some serious criticisms. We review important methodological developments as well as discuss problems with the approaches. We propose alternative designs that may be less controversial and present ideas for future research. Lastly, we provide recommendations about how these methods should be used in practice. C1 [Collins, John] George Mason Univ, Dept Rehabil Sci, Fairfax, VA USA. [Albert, Paul S.] Natl Canc Inst, Div Canc Epidemiol & Genet, Biostat Branch, 9609 Med Ctr Dr,Room E146, Rockville, MD 20850 USA. RP Albert, PS (reprint author), Natl Canc Inst, Div Canc Epidemiol & Genet, Biostat Branch, 9609 Med Ctr Dr,Room E146, Rockville, MD 20850 USA. EM albertp@mail.nih.gov FU Intramural program of the Eunice Kennedy Shriver National Institute of Child Health and Human Development FX Paul Albert's work was supported by the Intramural program of the Eunice Kennedy Shriver National Institute of Child Health and Human Development. NR 13 TC 0 Z9 0 U1 2 U2 2 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 530 WALNUT STREET, STE 850, PHILADELPHIA, PA 19106 USA SN 1054-3406 EI 1520-5711 J9 J BIOPHARM STAT JI J. Biopharm. Stat. PY 2016 VL 26 IS 6 SI SI BP 1078 EP 1082 DI 10.1080/10543406.2016.1226334 PG 5 WC Pharmacology & Pharmacy; Statistics & Probability SC Pharmacology & Pharmacy; Mathematics GA ED1HS UT WOS:000388596600007 PM 27548004 ER PT J AU Sachs, MC McShane, LM AF Sachs, Michael C. McShane, Lisa M. TI Issues in developing multivariable molecular signatures for guiding clinical care decisions SO JOURNAL OF BIOPHARMACEUTICAL STATISTICS LA English DT Article DE Biomarkers; biomarker signatures; personalized medicine ID GENE-EXPRESSION; RISK PREDICTION; LUNG-CANCER; CLASSIFIERS; VALIDATION AB Omics technologies that generate a large amount of molecular data characterizing biospecimens have the potential to provide information about patients' disease characteristics above and beyond standard clinical features. By combining information from a large number of features into a multivariable model, called a biomarker signature, there is the opportunity to identify distinct subgroups of patients for whom treatment decisions can be personalized. The key challenge is to derive a signature with good performance and appropriately characterize its performance. We summarize the key statistical issues and methods for developing and validating biomarker signatures, using examples from the literature for illustration. C1 [Sachs, Michael C.; McShane, Lisa M.] NCI, Biostat Branch, Biomet Res Program, 9609 Med Ctr Dr,MSC 9735, Bethesda, MD 20892 USA. RP Sachs, MC (reprint author), NCI, Biostat Branch, Biomet Res Program, 9609 Med Ctr Dr,MSC 9735, Bethesda, MD 20892 USA. EM michael.sachs@nih.gov NR 18 TC 0 Z9 0 U1 2 U2 2 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 530 WALNUT STREET, STE 850, PHILADELPHIA, PA 19106 USA SN 1054-3406 EI 1520-5711 J9 J BIOPHARM STAT JI J. Biopharm. Stat. PY 2016 VL 26 IS 6 SI SI BP 1098 EP 1110 DI 10.1080/10543406.2016.1226329 PG 13 WC Pharmacology & Pharmacy; Statistics & Probability SC Pharmacology & Pharmacy; Mathematics GA ED1HS UT WOS:000388596600009 PM 27561083 ER PT J AU Wu, MX Zhang, DC Liu, AY AF Wu, Mixia Zhang, Dianchen Liu, Aiyi TI Estimation of an accuracy index of a diagnostic biomarker when the reference biomarker is continuous and measured with error SO JOURNAL OF BIOPHARMACEUTICAL STATISTICS LA English DT Article DE Bias; diagnostic accuracy; Kendall's tau; measurement error; reliability coefficient ID GOLD STANDARD AB New biomarkers continue to be developed for the purpose of diagnosis, and their diagnostic performances are typically compared with an existing reference biomarker used for the same purpose. Considerable amounts of research have focused on receiver operating characteristic curves analysis when the reference biomarker is dichotomous. In the situation where the reference biomarker is measured on a continuous scale and dichotomization is not practically appealing, an index was proposed in the literature to measure the accuracy of a continuous biomarker, which is essentially a linear function of the popular Kendall's tau. We consider the issue of estimating such an accuracy index when the continuous reference biomarker is measured with errors. We first investigate the impact of measurement errors on the accuracy index, and then propose methods to correct for the bias due to measurement errors. Simulation results show the effectiveness of the proposed estimator in reducing biases. The methods are exemplified with hemoglobin A1c measurements obtained from both the central lab and a local lab to evaluate the accuracy of the mean data obtained from the metered blood glucose monitoring against the centrally measured hemoglobin A1c from a behavioral intervention study for families of youth with type 1 diabetes. C1 [Wu, Mixia] Beijing Univ Technol, Coll Appl Sci, Beijing, Peoples R China. [Zhang, Dianchen; Liu, Aiyi] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Biostat & Bioinformat Branch, Bethesda, MD USA. RP Liu, AY (reprint author), Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Biostat & Bioinformat Branch, Bethesda, MD USA.; Liu, AY (reprint author), Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, NIH, Biostat & Bioinformat Branch, 6710B Rockledge Dr,Room 3230, Bethesda, MD 20817 USA. EM Liua@mail.nih.gov OI Liu, Aiyi/0000-0002-6618-5082 FU Intramural Research Program of the National Institute of Child Health and Human Development, National Institutes of Health; General Program of Science and Technology Development Project of Beijing Municipal Education Commission [km201410005011] FX Research of Aiyi Liu was fully supported by the Intramural Research Program of the National Institute of Child Health and Human Development, National Institutes of Health. Research of Mixia Wu was partially supported by the General Program of Science and Technology Development Project of Beijing Municipal Education Commission (km201410005011). NR 9 TC 0 Z9 0 U1 1 U2 1 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 530 WALNUT STREET, STE 850, PHILADELPHIA, PA 19106 USA SN 1054-3406 EI 1520-5711 J9 J BIOPHARM STAT JI J. Biopharm. Stat. PY 2016 VL 26 IS 6 SI SI BP 1111 EP 1117 DI 10.1080/10543406.2016.1226330 PG 7 WC Pharmacology & Pharmacy; Statistics & Probability SC Pharmacology & Pharmacy; Mathematics GA ED1HS UT WOS:000388596600010 PM 27548574 ER PT J AU Ervin, AM Mkocha, H Munoz, B Dreger, K Dize, L Gaydos, C Quinn, TC West, SK AF Ervin, Ann-Margret Mkocha, Harran Munoz, Beatriz Dreger, Kurt Dize, Laura Gaydos, Charlotte Quinn, Thomas C. West, Sheila K. TI Surveillance and Azithromycin Treatment for Newcomers and Travelers Evaluation (ASANTE) Trial: Design and Baseline Characteristics SO OPHTHALMIC EPIDEMIOLOGY LA English DT Article DE Chlamydia trachomatis; community-based; randomized controlled trial; surveillance; Tanzania; trachoma ID CHLAMYDIA-TRACHOMATIS; MASS TREATMENT; RISK-FACTORS; TANZANIA; INFECTION; ELIMINATION; GAMBIA AB Purpose: Immigrants and travelers may be sources of re-emergent infection in trachoma-endemic communities close to trachoma elimination. The primary objective of the A Surveillance and Azithromycin Treatment for Newcomers and Travelers Evaluation (ASANTE) trial was to determine whether a newcomer and traveler surveillance and treatment program in addition to annual mass drug administration (MDA) would reduce Chlamydia trachomatis infection when compared to MDA alone. Methods: ASANTE was a randomized controlled trial in 52 communities in Kongwa, Tanzania. In 26 intervention communities, monitors treated everyone in new households, in-coming children and guardians in existing households, and all persons in households who had traveled between annual MDA events. A total of 26 usual practice communities received MDA only. Surveys of 100 1-9-year-olds from each community were conducted at baseline and every 6 months up to 2 years to assess clinical trachoma and C. trachomatis infection. Data on demographics and environmental factors were also collected. Results: Mean prevalences of trachomatous inflammation - follicular (TF) and C. trachomatis were equivalent between the two arms (5.2% and 3.7% in intervention, and 4.9% and 3.6% in usual practice communities, respectively). Of 318 children with TF, 36.5% tested positive for C. trachomatis. TF prevalence was higher among households without a bicycle (p = 0.03) and lower with increasing child's age (p < 0.001). Infection prevalence was higher among households >30 minutes from water (p = 0.015). TF and infection prevalence decreased with increasing years of education (p = 0.004 and p = 0.002, respectively). Conclusion: The ASANTE trial will inform guidance on the surveillance and treatment of persons traveling or newly arriving to communities hypo-endemic for trachoma. C1 [Ervin, Ann-Margret; Munoz, Beatriz; Dreger, Kurt; West, Sheila K.] Johns Hopkins Univ, Wilmer Eye Inst, Dana Ctr Prevent Ophthalmol, Baltimore, MD 21218 USA. [Ervin, Ann-Margret] Johns Hopkins Bloomberg Sch Publ Hlth, Dept Epidemiol, 615 N Wolfe St,E6146, Baltimore, MD 21205 USA. [Mkocha, Harran] Kongwa Trachoma Project, Kongwa, Tanzania. [Dize, Laura; Gaydos, Charlotte; Quinn, Thomas C.] Johns Hopkins Univ, Dept Med, Int Chlamydia Lab, Baltimore, MD USA. [Quinn, Thomas C.] NIAID, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA. RP Ervin, AM (reprint author), Johns Hopkins Bloomberg Sch Publ Hlth, Dept Epidemiol, 615 N Wolfe St,E6146, Baltimore, MD 21205 USA. EM aervin@jhu.edu FU National Eye Institute, National Institutes of Health [U10EY022584]; Division of Intramural Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health FX Financial support for this study was received from: the National Eye Institute, National Institutes of Health, U10EY022584 and the Division of Intramural Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health. NR 14 TC 1 Z9 1 U1 0 U2 0 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 530 WALNUT STREET, STE 850, PHILADELPHIA, PA 19106 USA SN 0928-6586 EI 1744-5086 J9 OPHTHAL EPIDEMIOL JI Ophthalmic Epidemiol. PY 2016 VL 23 IS 6 BP 347 EP 353 DI 10.1080/09286586.2016.1238947 PG 7 WC Ophthalmology SC Ophthalmology GA ED1EU UT WOS:000388588300002 PM 27820670 ER PT B AU Palomo, J Marquez, J Laguna, P AF Palomo, Jesus Marquez, Jeronimo Laguna, Pilar BE Savona, EU Riccardi, M Berlusconi, G TI From drug trafficking to wholesale trade business Organised crime infiltration in Spain SO ORGANISED CRIME IN EUROPEAN BUSINESSES SE Routledge Studies in Crime and Society LA English DT Article; Book Chapter C1 [Palomo, Jesus; Laguna, Pilar] Rey Juan Carlos Univ, Dept Business Adm, Madrid, Spain. [Palomo, Jesus] Georgetown Univ, Washington, DC 20057 USA. [Palomo, Jesus] NATO Def Coll, Rome, Italy. [Palomo, Jesus] CNR, I-00185 Rome, Italy. [Palomo, Jesus] Duke Univ, Durham, NC 27706 USA. [Palomo, Jesus] Univ Calif Santa Cruz, Santa Cruz, CA 95064 USA. [Palomo, Jesus] NIEHS, POB 12233, Res Triangle Pk, NC 27709 USA. [Palomo, Jesus] Danish Inst Social Res, Copenhagen, Denmark. [Marquez, Jeronimo] Rey Juan Carlos Univ, Madrid, Spain. [Laguna, Pilar] Rey Juan Carlos Univ, Law & Social Sci Sch, Madrid, Spain. [Laguna, Pilar] Assoc Grad Natl Def Higher Studies, Madrid, Spain. RP Palomo, J (reprint author), Rey Juan Carlos Univ, Dept Business Adm, Madrid, Spain. NR 79 TC 0 Z9 0 U1 2 U2 2 PU ROUTLEDGE PI ABINGDON PA 2 PARK SQ, MILTON PARK, ABINGDON OX14 4RN, OXFORD, ENGLAND BN 978-1-315-64061-7; 978-1-138-19109-9 J9 ROUT STUD CRIM SOC PY 2016 BP 64 EP 83 PG 20 WC Business; Criminology & Penology SC Business & Economics; Criminology & Penology GA BG4DN UT WOS:000388676800006 ER PT B AU Sood, A AF Sood, Anubha BE Luhrmann, TM Marrow, J TI Madness Experienced as Faith Temple Healing in North India SO OUR MOST TROUBLING MADNESS: CASE STUDIES IN SCHIZOPHRENIA ACROSS CULTURES SE Ethnographic Studies in Subjectivity LA English DT Article; Book Chapter C1 [Sood, Anubha] Southern Methodist Univ, Anthropol, Dallas, TX 75275 USA. [Sood, Anubha] NIMH, Bethesda, MD 20814 USA. RP Sood, A (reprint author), Southern Methodist Univ, Anthropol, Dallas, TX 75275 USA.; Sood, A (reprint author), NIMH, Bethesda, MD 20814 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU UNIV CALIFORNIA PRESS PI OAKLAND PA 155 GRAND AVE, SUITE 400, OAKLAND, CA 94612-3758 USA BN 978-0-520-29109-6; 978-0-520-96494-5; 978-0-520-29108-9 J9 ETHNOG STUD SUBJ PY 2016 VL 11 BP 127 EP 138 PG 12 WC Anthropology; Social Sciences, Biomedical SC Anthropology; Biomedical Social Sciences GA BG3UA UT WOS:000388299600010 ER PT S AU Roy, S Chou, YY Jog, A Butman, JA Pham, DL AF Roy, Snehashis Chou, Yi-Yu Jog, Amod Butman, John A. Pham, Dzung L. BE Tsaftaris, SA Gooya, A Frangi, AF Prince, JL TI Patch Based Synthesis of Whole Head MR Images: Application To EPI Distortion Correction SO SIMULATION AND SYNTHESIS IN MEDICAL IMAGING, SASHIMI 2016 SE Lecture Notes in Computer Science LA English DT Proceedings Paper CT 1st International Workshop on Simulation and Synthesis in Medical Imaging (SASHIMI) CY OCT 21, 2016 CL Athens, GREECE DE Image synthesis; Patches; Distortion correction; EPI ID REGISTRATION; BRAIN; SEGMENTATION; DIFFUSION; CT AB Different magnetic resonance imaging pulse sequences are used to generate image contrasts based on physical properties of tissues, which provide different and often complementary information about them. Therefore multiple image contrasts are useful for multimodal analysis of medical images. Often, medical image processing algorithms are optimized for particular image contrasts. If a desirable contrast is unavailable, contrast synthesis (or modality synthesis) methods try to "synthesize" the unavailable constrasts from the available ones. Most of the recent image synthesis methods generate synthetic brain images, while whole head magnetic resonance (MR) images can also be useful for many applications. We propose an atlas based patch matching algorithm to synthesize T-2-w whole head (including brain, skull, eyes etc.) images from T-1-w images for the purpose of distortion correction of diffusion weighted MR images. The geometric distortion in diffusion MR images due to inhomogeneous B-0 magnetic field are often corrected by non-linearly registering the corresponding b = 0 image with zero diffusion gradient to an undistorted T-2-w image. We show that our synthetic T-2-w images can be used as a template in absence of a real T-2-w image. Our patch based method requires multiple atlases with T-1 and T-2 to be registered to a given target T1. Then for every patch on the target, multiple similar looking matching patches are found on the atlas T-1 images and corresponding patches on the atlas T-2 images are combined to generate a synthetic T-2 of the target. We experimented on image data obtained from 44 patients with traumatic brain injury (TBI), and showed that our synthesized T-2 images produce more accurate distortion correction than a state-of-the-art registration based image synthesis method. C1 [Roy, Snehashis; Chou, Yi-Yu; Pham, Dzung L.] Henry Jackson Fdn, Ctr Neurosci & Regenerat Med, Bethesda, MD 20817 USA. [Jog, Amod] Johns Hopkins Univ, Dept Comp Sci, Baltimore, MD 21218 USA. [Butman, John A.] NIH, Dept Diagnost Radiol, Bldg 10, Bethesda, MD 20892 USA. RP Roy, S (reprint author), Henry Jackson Fdn, Ctr Neurosci & Regenerat Med, Bethesda, MD 20817 USA. EM snehashis.roy@nih.gov NR 23 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER INT PUBLISHING AG PI CHAM PA GEWERBESTRASSE 11, CHAM, CH-6330, SWITZERLAND SN 0302-9743 BN 978-3-319-46630-9; 978-3-319-46629-3 J9 LECT NOTES COMPUT SC PY 2016 VL 9968 BP 146 EP 156 DI 10.1007/978-3-319-46630-9_15 PG 11 WC Computer Science, Artificial Intelligence; Computer Science, Theory & Methods; Radiology, Nuclear Medicine & Medical Imaging SC Computer Science; Radiology, Nuclear Medicine & Medical Imaging GA BG4OG UT WOS:000389020600015 ER PT J AU Perreault, JR Geigle, PR Gorman, PH Scott, WH AF Perreault, J. R. Geigle, P. R. Gorman, P. H. Scott, W. H. TI Improvement in weight loss and ambulation outcomes after gastric sleeve surgery for a person with chronic motor-incomplete tetraplegia: clinical case report SO SPINAL CORD LA English DT Article ID SPINAL-CORD-INJURY; OBESITY; PEOPLE; ADULTS AB Objective: To measure body mass index (BMI) and ambulation changes for a morbidly obese, 47-year-old man with chronic motor-incomplete tetraplegia after gastric sleeve surgery. Design/Method: A morbidly obese man, BMI = 44 kg m(-2), with chronic C5 AIS D tetraplegia underwent elective gastric sleeve surgery. Assessment of BMI and function via the 6-minute walk test (6MWT), 10-meter walk test (10MWT) and ambulation parameters (CIR Systems/GAITRite, Franklin, NJ, USA) was performed preoperatively and at 12, 24, 36 and 52 weeks postoperatively, and additionally after 3 weeks of both a prescribed coached (3x /week facility based) and a non-coached (3 x /week home based) walking program initiated at 52 weeks. A step activity monitor assessed daily ambulation preoperatively, prior to and during the third and sixth week of the walking program. Results: Results included a 34.3% peak BMI decrease at 52 weeks post surgery and a peak increase in 6MWT distance of 58% at 52 weeks post surgery, 10MWT preferred speed of 56% at 55 weeks and step activity monitor of 82% at 58 weeks post surgery. At 58 weeks, gait data demonstrated a decrease in double limb stance of 38% and decrease in base of support of 72%. Conclusion/Clinical Relevance: This empirical case assessment of BMI and functional mobility before and after gastric sleeve surgery may encourage further investigation into mobility and general health effects post gastric procedures for people with chronic motor-incomplete spinal cord injury. C1 [Perreault, J. R.] NIH, Bldg 10, Bethesda, MD 20892 USA. [Geigle, P. R.; Gorman, P. H.; Scott, W. H.] Univ Maryland, Sch Med, Baltimore, MD 21201 USA. [Geigle, P. R.; Gorman, P. H.] Univ Maryland, Rehabil & Orthopaed Inst, Baltimore, MD 21201 USA. [Gorman, P. H.] VA Maryland Healthcare Syst, Baltimore, MD USA. RP Geigle, PR (reprint author), Univ Maryland Rehabil & Orthopaed, 2200 Kernan Dr, Baltimore, MD 21207 USA. EM pgeigle@umm.edu NR 16 TC 1 Z9 1 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1362-4393 EI 1476-5624 J9 SPINAL CORD JI Spinal Cord PY 2016 VL 54 IS 9 BP 750 EP 753 DI 10.1038/sc.2016.22 PG 4 WC Clinical Neurology; Rehabilitation SC Neurosciences & Neurology; Rehabilitation GA DW3ZK UT WOS:000383581400021 PM 26927296 ER PT J AU Sarker, H Tyburski, M Rahman, MM Hovsepian, K Sharmin, M Epstein, DH Preston, KL Furr-Holden, CD Milam, A Nahum-Shani, I al'Absi, M Kumar, S AF Sarker, Hillol Tyburski, Matthew Rahman, Md. Mahbubur Hovsepian, Karen Sharmin, Moushumi Epstein, David H. Preston, Kenzie L. Furr-Holden, C. Debra Milam, Adam Nahum-Shani, Inbal al'Absi, Mustafa Kumar, Santosh GP ACM TI Finding Significant Stress Episodes in a Discontinuous Time Series of Rapidly Varying Mobile Sensor Data SO 34TH ANNUAL CHI CONFERENCE ON HUMAN FACTORS IN COMPUTING SYSTEMS, CHI 2016 LA English DT Proceedings Paper CT 34th Annual CHI Conference on Human Factors in Computing Systems (CHI4GOOD) CY MAY 07-12, 2016 CL San Jose, CA SP Assoc Comp Machinery, SIG CHI DE Mobile Health (mHealth); Intervention; Stress Management ID CONSERVATION; DISORDERS; RESOURCES; RECOVERY; SYSTEM; MOOD AB Management of daily stress can be greatly improved by delivering sensor-triggered just-in-time interventions (JITIs) on mobile devices. The success of such JITIs critically depends on being able to mine the time series of noisy sensor data to find the most opportune moments. In this paper, we propose a time series pattern mining method to detect significant stress episodes in a time series of discontinuous and rapidly varying stress data. We apply our model to 4 weeks of physiological, GPS, and activity data collected from 38 users in their natural environment to discover patterns of stress in real-life. We find that the duration of a prior stress episode predicts the duration of the next stress episode and stress in mornings and evenings is lower than during the day. We then analyze the relationship between stress and objectively rated disorder in the surrounding neighborhood and develop a model to predict stressful episodes. C1 [Sarker, Hillol; Rahman, Md. Mahbubur; Kumar, Santosh] Univ Memphis, Memphis, TN 38152 USA. [Tyburski, Matthew; Epstein, David H.; Preston, Kenzie L.] NIDA, Intramural Res Program, Bethesda, MD USA. [Hovsepian, Karen] Troy Univ, Troy, NY USA. [Sharmin, Moushumi] Western Washington Univ, Bellingham, WA 98225 USA. [Furr-Holden, C. Debra; Milam, Adam] Johns Hopkins Bloomberg Sch Publ Hlth, Baltimore, MD USA. [Nahum-Shani, Inbal] Univ Michigan, Ann Arbor, MI 48109 USA. [al'Absi, Mustafa] Univ Minnesota, Sch Med, Minneapolis, MN 55455 USA. RP Sarker, H (reprint author), Univ Memphis, Memphis, TN 38152 USA. EM hsarker@memphis.edu; matthew.tyburski@nih.gov; mmrahman@memphis.edu; khovsepian@troy.edu; moushumi.sharmin@wwu.edu; depstein@intra.nida.nih.gov; kpreston@intra.nida.nih.gov; dholden@jhsph.edu; amilam@jhsph.edu; inbal@umich.edu; malabsi@umn.edu; santosh.kumar@memphis.edu NR 64 TC 2 Z9 2 U1 0 U2 0 PU ASSOC COMPUTING MACHINERY PI NEW YORK PA 1515 BROADWAY, NEW YORK, NY 10036-9998 USA BN 978-1-4503-3362-7 PY 2016 BP 4489 EP 4501 DI 10.1145/2858036.2858218 PG 13 WC Computer Science, Artificial Intelligence; Computer Science, Software Engineering; Computer Science, Theory & Methods SC Computer Science GA BF3EQ UT WOS:000380532904044 ER PT J AU Baljevic, M Dumitriu, B Lee, JW Paietta, EM Wiernik, PH Racevskis, J Chen, C Stein, EM Gallagher, RE Rowe, JM Appelbaum, FR Powell, BL Larson, RA Coutre, SE Lancet, J Litzow, MR Luger, SM Young, NS Tallman, MS AF Baljevic, Muhamed Dumitriu, Bogdan Lee, Ju-Whei Paietta, Elisabeth M. Wiernik, Peter H. Racevskis, Janis Chen, Christina Stein, Eytan M. Gallagher, Robert E. Rowe, Jacob M. Appelbaum, Frederick R. Powell, Bayard L. Larson, Richard A. Coutre, Steven E. Lancet, Jeffrey Litzow, Mark R. Luger, Selina M. Young, Neal S. Tallman, Martin S. TI Telomere Length Recovery: A Strong Predictor of Overall Survival in Acute Promyelocytic Leukemia SO ACTA HAEMATOLOGICA LA English DT Article DE Acute promyelocytic leukemia; Disease risk factors; Telomere length ID TRANS-RETINOIC ACID; BONE-MARROW FAILURE; ARSENIC TRIOXIDE; DYSKERATOSIS-CONGENITA; REVERSE-TRANSCRIPTASE; APLASTIC-ANEMIA; CELL-DEATH; MUTATIONS; CANCER; GENE AB Telomeres are the capping ends of chromosomes that protect the loss of genetic material and prevent chromosomal instability. In human tissue-specific stem/progenitor cells, telomere length (TL) is maintained by the telomerase complex, which consists of a reverse transcriptase catalytic subunit (TERT) and an RNA template (TERC). Very short telomeres and loss-of-function mutations in the TERT and TERC genes have been reported in acute myeloid leukemia, but the role of telomeres in acute promyelocytic leukemia (APL) has not been well established. We report the results for a large cohort of 187 PML/RAR alpha-positive APL patients. No germline mutations in the TERT or TERC genes were identified. Codon 279 and 1062 TERT polymorphisms were present at a frequency similar to that in the general population. TL measured in blood or marrow mononuclear cells at diagnosis was significantly shorter in the APL patients than in healthy volunteers, and shorter telomeres at diagnosis were significantly associated with high-risk disease. For patients who achieved complete remission, the median increase in TL from diagnosis to remission (delta TL) was 2.0 kilobase (kb), and we found delta TL to be the most powerful predictor of overall survival when compared with well-established risk factors for poor outcomes in APL. (C) 2016 S. Karger AG, Basel C1 [Baljevic, Muhamed] Univ Nebraska, Med Ctr, Div Hematol Oncol, Omaha, NE USA. [Dumitriu, Bogdan; Chen, Christina; Young, Neal S.] NHLBI, NIH, Bethesda, MD USA. [Lee, Ju-Whei] Dana Farber Canc Inst, ECOG ACRIN Biostat Ctr, Boston, MA 02115 USA. [Paietta, Elisabeth M.; Racevskis, Janis; Gallagher, Robert E.] Montefiore Med Ctr, 111 E 210th St, Bronx, NY 10467 USA. [Wiernik, Peter H.] Beth Israel Deaconess Med Ctr, New York, NY 10003 USA. [Stein, Eytan M.; Tallman, Martin S.] Mem Sloan Kettering Canc Ctr, 1275 York Ave, New York, NY 10021 USA. [Rowe, Jacob M.] Northwestern Univ, Rambam Med Ctr, Chicago, IL 60611 USA. [Larson, Richard A.] Univ Chicago, Chicago, IL 60637 USA. [Appelbaum, Frederick R.] Fred Hutchinson Canc Res Ctr, 1124 Columbia St, Seattle, WA 98104 USA. [Powell, Bayard L.] Wake Forest Baptist Comprehens Canc Ctr, Winston Salem, NC USA. [Coutre, Steven E.] Stanford Univ, Stanford, CA 94305 USA. [Lancet, Jeffrey] H Lee Moffitt Canc Ctr & Res Inst, Tampa, FL USA. [Litzow, Mark R.] Mayo Clin, Rochester, MN USA. [Luger, Selina M.] Univ Penn, Philadelphia, PA 19104 USA. RP Tallman, MS (reprint author), Weill Cornell Med Coll, Mem Sloan Kettering Canc Ctr, Dept Med, Leukemia Serv, 1275 York Ave, New York, NY 10065 USA. EM TallmanM@mskcc.org OI Larson, Richard/0000-0001-9168-3203 FU Public Health Service Grants [CA180820, CA180794, CA189859, CA180791, CA180816, CA180819, CA180821, CA180790]; National Cancer Institute, National Institutes of Health and the Department of Health and Human Services FX This study was conducted by the ECOG-ACRIN Cancer Research Group (Robert L. Comis, MD, and Mitchell D. Schnall, MD, PhD, Group Co-Chairs) and supported in part by Public Health Service Grants CA180820, CA180794, CA189859, CA180791, CA180816, CA180819, CA180821 and CA180790 and the National Cancer Institute, National Institutes of Health and the Department of Health and Human Services. Its content is solely the responsibility of the authors and does not necessarily represent the official views of the National Cancer Institute. NR 25 TC 0 Z9 0 U1 1 U2 1 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 0001-5792 EI 1421-9662 J9 ACTA HAEMATOL-BASEL JI Acta Haematol. PY 2016 VL 136 IS 4 BP 210 EP 218 DI 10.1159/000448160 PG 9 WC Hematology SC Hematology GA EC5FJ UT WOS:000388158200003 PM 27632567 ER EF