FN Thomson Reuters Web of Science™ VR 1.0 PT B AU Xie, J Gao, JH Michalski, M Chen, XY AF Xie, Jin Gao, Jinhao Michalski, Mark Chen, Xiaoyuan BE Chen, X TI Nanoparticle Surface Modification and Bioconjugation SO NANOPLATFORM-BASED MOLECULAR IMAGING LA English DT Article; Book Chapter ID WALLED CARBON NANOTUBES; SEMICONDUCTOR QUANTUM DOTS; IRON-OXIDE NANOPARTICLES; RESONANCE ENERGY-TRANSFER; NONCOVALENT SIDEWALL-FUNCTIONALIZATION; MESOPOROUS SILICA NANOPARTICLES; DIIMIDE-ACTIVATED AMIDATION; MAGNETIC NANOPARTICLES; IN-VIVO; BIOMEDICAL APPLICATIONS C1 [Xie, Jin; Gao, Jinhao; Michalski, Mark; Chen, Xiaoyuan] Stanford Univ, Sch Med, Dept Radiol, Mol Imaging Program Stanford, Stanford, CA 94305 USA. [Xie, Jin; Gao, Jinhao; Michalski, Mark; Chen, Xiaoyuan] Stanford Univ, Sch Med, Dept Radiol, Bio X Program, Stanford, CA 94305 USA. [Xie, Jin; Chen, Xiaoyuan] Natl Inst Biomed Imaging & Bioengn, Lab Mol Imaging & Nanomed, NIH, Bethesda, MD USA. RP Xie, J (reprint author), Stanford Univ, Sch Med, Dept Radiol, Mol Imaging Program Stanford, Stanford, CA 94305 USA. NR 149 TC 1 Z9 1 U1 1 U2 2 PU BLACKWELL SCIENCE PUBL PI OXFORD PA OSNEY MEAD, OXFORD OX2 0EL, ENGLAND BN 978-0-470-76703-0; 978-0-470-52115-1 PY 2011 BP 47 EP 73 D2 10.1002/9780470767047 PG 27 WC Nanoscience & Nanotechnology; Radiology, Nuclear Medicine & Medical Imaging SC Science & Technology - Other Topics; Radiology, Nuclear Medicine & Medical Imaging GA BA5SW UT WOS:000336989900004 ER PT B AU Zabow, G Koretsky, A AF Zabow, Gary Koretsky, Alan BE Chen, X TI Microfabricated Multispectral MRI Contrast Agents SO NANOPLATFORM-BASED MOLECULAR IMAGING LA English DT Article; Book Chapter ID SUPERPARAMAGNETIC IRON-OXIDE; RESONANCE-IMAGING MEMRI; SINGLE MAMMALIAN-CELLS; MAGNETIC-RESONANCE; IN-VIVO; CELLULAR MRI; STEM-CELLS; PROTON-EXCHANGE; PARACEST AGENTS; RODENT BRAIN C1 [Zabow, Gary; Koretsky, Alan] NINCDS, Lab Funct & Mol Imaging, NIH, Bethesda, MD 20892 USA. RP Zabow, G (reprint author), NINCDS, Lab Funct & Mol Imaging, NIH, Bethesda, MD 20892 USA. RI Koretsky, Alan/C-7940-2015 OI Koretsky, Alan/0000-0002-8085-4756 NR 82 TC 0 Z9 0 U1 0 U2 1 PU BLACKWELL SCIENCE PUBL PI OXFORD PA OSNEY MEAD, OXFORD OX2 0EL, ENGLAND BN 978-0-470-76703-0; 978-0-470-52115-1 PY 2011 BP 375 EP 397 D2 10.1002/9780470767047 PG 23 WC Nanoscience & Nanotechnology; Radiology, Nuclear Medicine & Medical Imaging SC Science & Technology - Other Topics; Radiology, Nuclear Medicine & Medical Imaging GA BA5SW UT WOS:000336989900017 ER PT J AU Bhirde, A Xie, J Swierczewska, M Chen, XY AF Bhirde, Ashwinkumar Xie, Jin Swierczewska, Maggie Chen, Xiaoyuan TI Nanoparticles for cell labeling SO NANOSCALE LA English DT Article ID IRON-OXIDE NANOPARTICLES; MESENCHYMAL STEM-CELLS; REPORTER GENE-EXPRESSION; MRI CONTRAST AGENTS; IN-VIVO TRACKING; QUANTUM DOTS; MAGNETIC-RESONANCE; TRANSPLANTED CELLS; LIVE CELL; INORGANIC NANOPARTICLES AB Cell based therapeutics are emerging as powerful regimens. To better understand the migration and proliferation mechanisms of implanted cells, a means to track cells in living subjects is essential, and to achieve that, a number of cell labeling techniques have been developed. Nanoparticles, with their superior physical properties, have become the materials of choice in many investigations along this line. Owing to inherent magnetic, optical or acoustic attributes, these nanoparticles can be detected by corresponding imaging modalities in living subjects at a high spatial and temporal resolution. These features allow implanted cells to be separated from host cells; and have advantages over traditional histological methods, as they permit non-invasive, real-time tracking in vivo. This review attempts to give a summary of progress in using nanotechnology to monitor cell trafficking. We will focus on direct cell labeling techniques, in which cells ingest nanoparticles that bear traceable signals, such as iron oxide or quantum dots. Ferritin and MagA reporter genes that can package endogenous iron or iron supplement into iron oxide nanoparticles will also be discussed. C1 [Bhirde, Ashwinkumar; Xie, Jin; Swierczewska, Maggie; Chen, Xiaoyuan] NIBIB, LOMIN, NIH, Bethesda, MD 20892 USA. RP Chen, XY (reprint author), NIBIB, LOMIN, NIH, Bethesda, MD 20892 USA. EM shawn.chen@nih.gov RI Xie, Jin/E-8193-2010 FU NIH, National Institute of Biomedical Imaging and Bioengineering FX This research was supported by the Intramural Research Program of the NIH, including the National Institute of Biomedical Imaging and Bioengineering. NR 155 TC 115 Z9 117 U1 5 U2 52 PU ROYAL SOC CHEMISTRY PI CAMBRIDGE PA THOMAS GRAHAM HOUSE, SCIENCE PARK, MILTON RD, CAMBRIDGE CB4 0WF, CAMBS, ENGLAND SN 2040-3364 J9 NANOSCALE JI Nanoscale PY 2011 VL 3 IS 1 BP 142 EP 153 DI 10.1039/c0nr00493f PG 12 WC Chemistry, Multidisciplinary; Nanoscience & Nanotechnology; Materials Science, Multidisciplinary; Physics, Applied SC Chemistry; Science & Technology - Other Topics; Materials Science; Physics GA 706FY UT WOS:000286204600011 PM 20938522 ER PT J AU Xing, RJ Zhang, F Xie, J Aronova, M Zhang, GF Guo, N Huang, XL Sun, XL Liu, G Bryant, LH Bhirde, A Liang, A Hou, YL Leapman, RD Sun, SH Chen, XY AF Xing, Ruijun Zhang, Fan Xie, Jin Aronova, Maria Zhang, Guofeng Guo, Ning Huang, Xinglu Sun, Xiaolian Liu, Gang Bryant, L. Henry Bhirde, Ashwinkumar Liang, Amy Hou, Yanglong Leapman, Richard D. Sun, Shouheng Chen, Xiaoyuan TI Polyaspartic acid coated manganese oxide nanoparticles for efficient liver MRI SO NANOSCALE LA English DT Article ID MAGNETIC NANOPARTICLES; MNO NANOPARTICLES; FUNCTIONALIZATION; DELIVERY; CONTRAST; CANCER AB We report in this communication a simple, facile surface modification strategy to transfer hydrophobic manganese oxide nanoparticles (MONPs) into water by using polyaspartic acid (PASP). We systematically investigated the effect of the size of PASP-MONPs on MRI of normal liver and found that the particles with a core size of 10 nm exhibited greater enhancement than those with larger core sizes. C1 [Xing, Ruijun; Zhang, Fan; Xie, Jin; Guo, Ning; Huang, Xinglu; Liu, Gang; Liang, Amy; Chen, Xiaoyuan] NIBIB, Lab Mol Imaging & Nanomed LOMIN, NIH, Bethesda, MD 20892 USA. [Xing, Ruijun; Bhirde, Ashwinkumar; Hou, Yanglong] Peking Univ, Coll Engn, Dept Mat Sci & Engn, Beijing 100871, Peoples R China. [Aronova, Maria; Zhang, Guofeng; Leapman, Richard D.] NIBIB, Lab Cellular Imaging & Macromol Biophys, NIH, Bethesda, MD 20892 USA. [Sun, Xiaolian; Sun, Shouheng] Brown Univ, Dept Chem, Providence, RI 02912 USA. [Bryant, L. Henry] NIH, Lab Diagnost Radiol Res CC, Bethesda, MD 20892 USA. RP Chen, XY (reprint author), NIBIB, Lab Mol Imaging & Nanomed LOMIN, NIH, Bethesda, MD 20892 USA. EM shawn.chen@nih.gov RI Hou, Yanglong/B-8241-2012; Hou, Yanglong/B-8688-2012 FU National Institute of Biomedical Imaging and Bioengineering (NIBIB), NCI R00 [CA153772]; National Nature Science of Foundation of China (NSFC) [51172005, 81028009]; National Basic Research Program of China [2010CB934602]; China Scholarship Council FX This research was supported in part by the Intramural Research Program of the National Institute of Biomedical Imaging and Bioengineering (NIBIB), an NCI R00 grant CA153772 (to J.X.), the National Nature Science of Foundation of China (NSFC) (51172005 and 81028009), and the National Basic Research Program of China (2010CB934602). R.X. is partially supported by the China Scholarship Council. NR 14 TC 22 Z9 24 U1 3 U2 37 PU ROYAL SOC CHEMISTRY PI CAMBRIDGE PA THOMAS GRAHAM HOUSE, SCIENCE PARK, MILTON RD, CAMBRIDGE CB4 0WF, CAMBS, ENGLAND SN 2040-3364 J9 NANOSCALE JI Nanoscale PY 2011 VL 3 IS 12 BP 4943 EP 4945 DI 10.1039/c1nr11242b PG 3 WC Chemistry, Multidisciplinary; Nanoscience & Nanotechnology; Materials Science, Multidisciplinary; Physics, Applied SC Chemistry; Science & Technology - Other Topics; Materials Science; Physics GA 855ST UT WOS:000297585500006 PM 22064945 ER PT B AU Kobayashi, H AF Kobayashi, H. BE Laudon, M Romanowicz, B TI Pharmacokinetics and clearance properties of nano-sized particles and molecules as multi-modality imaging agents: Considerations and caveats SO NANOTECHNOLOGY 2011: BIO SENSORS, INSTRUMENTS, MEDICAL, ENVIRONMENT AND ENERGY, NSTI-NANOTECH 2011, VOL 3 LA English DT Proceedings Paper CT NSTI Nanotechnology Conference and Expo CY JUN 13-16, 2011 CL Boston, MA SP Clean Technol & Sustainable Ind Org, European Patent Off, Greenberg Traurig, Innovat & Mat Sci Inst, Jackson Walker LLP, Linde Nanomaterials, Lockheed Martin, Nano Sci & Technol Inst, Nano Tech Japan, NanoEurope Fair & Conf, Nanpolis Suzhou, Suzhou Nanotech Co Ltd, Natl Inst Standards & Technol, Ctr Nanoscale Sci & Technol, Fraunhofer, Res Germany, TechConnect, Technol Innovat Program, Canadian Trade Commiss Serv, Italian Trade Commiss DE nanomaterials; imaging; clearance; nano-toxicology; dendrimer ID MRI CONTRAST AGENTS; QUANTUM DOTS; CORES; FV AB Nano-sized particles and molecules possess enormous potential as diagnostic imaging agents and hold promise for the development of multimodality agents with both imaging and therapeutic capabilities. Yet, some of the most promising nano-materials currently under investigation demonstrate prolonged tissue retention and contain heavy metals. This presents serious concerns for toxicity and additionally, prolonged particle retention may interfere with diagnostic imaging and testing modalities. The creation of nano-sized particles and molecules with optimal pharmacokinetics and clearance characteristics will minimize toxicity risks by reducing the duration of exposure to these agents. Given that many types of nano materials possess easily modifiable surface chemistry, if nanoparticle characteristics associated with optimal pharmacokinetics and clearance from the body were well established, it would be feasible to design and create agents with more favorable clearance properties. In this talk, based on our experiences of dendrimer-based nano-sized MRI/Optical/Nuclear multimodality imaging agents, I will discuss the physiologic clearance of nano-sized particle and molecule, especially focusing on renal mechanisms, as well as provides an extended view of current research investigating clearance of other types of nano-sized particles and molecules, including dendrimers, quantum dots, and carbon, gold, and silica-based nanoparticles. C1 [Kobayashi, H.] NCI, Mol Imaging Program, NIH, Bldg 10,Rm B3B69,10 Ctr Dr, Bethesda, MD 20892 USA. RP Kobayashi, H (reprint author), NCI, Mol Imaging Program, NIH, Bldg 10,Rm B3B69,10 Ctr Dr, Bethesda, MD 20892 USA. EM kobayash@mail.nih.gov NR 19 TC 0 Z9 0 U1 0 U2 0 PU CRC PRESS-TAYLOR & FRANCIS GROUP PI BOCA RATON PA 6000 BROKEN SOUND PARKWAY NW, STE 300, BOCA RATON, FL 33487-2742 USA BN 978-1-4398-7138-6 PY 2011 BP 125 EP 128 PG 4 WC Energy & Fuels; Engineering, Environmental; Nanoscience & Nanotechnology; Medicine, Research & Experimental; Materials Science, Biomaterials SC Energy & Fuels; Engineering; Science & Technology - Other Topics; Research & Experimental Medicine; Materials Science GA BG9XC UT WOS:000394061000034 ER PT J AU Ahmed, SB Sghaier, RM Guesmi, F Kaabi, B Mejri, M Attia, H Laouini, D Smaali, I AF Ahmed, S. Ben Hadj Sghaier, R. M. Guesmi, F. Kaabi, B. Mejri, M. Attia, H. Laouini, D. Smaali, I. TI Evaluation of antileishmanial, cytotoxic and antioxidant activities of essential oils extracted from plants issued from the leishmaniasis-endemic region of Sned (Tunisia) SO NATURAL PRODUCT RESEARCH LA English DT Article DE leishmaniasis; essential oils; antiparasitic; antioxidant; cytotoxicity; GC-MS ID CHEMICAL-COMPOSITION; VOLATILE COMPONENTS; CUTANEOUS LEISHMANIASIS; RUTA-CHALEPENSIS; IN-VITRO; L.; CONSTITUENTS; ANTIBACTERIAL; GROWTH AB In this study, we tested 10 essential oils (EOs) extracted from 10 plants issued from Sned region (Tunisia) to evaluate both their leishmanicidal effects against Leishmania major and L. infantum, and their cytotoxicity against murine macrophage cell line RAW 264.7 (ATCC, TIB-71). The antioxidant activity was also monitored by the DDPH method, while the chemical composition of active EO was assessed by GC-MS analysis. The results showed that the EOs obtained from Thymus hirtus sp. algeriensis (rich on monoterpenoids, especially linalool at 17.62% and camphor at 13.82%) is significantly active against both L. major and L. infantum, whereas Ruta chalepensis EO (rich on 2-undecanone at 84.28%) is only active against L. infantum. Both oil extracts showed low cytotoxicity towards murine macrophages. The characteristic ratios (IC80 Raw264.7 cells/IC50 L. infantum and IC80 Raw264.7 cells/IC50 L. major) were, respectively, 2.7 and 1.57 for T. hirtus sp. algeriensis, and 1.34 and 0.19 for R. chalepensis. However, when measuring the antioxidant effects (DDPH method), the two latter EOs presented a moderate 2,2-diphenyl-2-picrylhydrazyl hydrate scavenging effects compared to EOs from Eucaliptus globulus, Pinus halepensis, Pituranthos tortuosus, Rosmarinus officinalis, Tetraclinis articulata or to BHT. C1 [Ahmed, S. Ben Hadj; Guesmi, F.] Fac Sci Gafsa, Dept Biol, Gafsa, Tunisia. [Sghaier, R. M.; Attia, H.; Laouini, D.] Inst Pasteur Tunis, Tunis 1002, Tunisia. [Sghaier, R. M.; Attia, H.; Laouini, D.] NIAID, TMRC, NIH, Bethesda, MD USA. [Sghaier, R. M.; Attia, H.; Laouini, D.] CNRS France, Lab Int Associe Ingn Biomol, Paris, France. [Sghaier, R. M.; Attia, H.; Laouini, D.] WHO Collaborating Ctr Leishmaniais, Lab Immunopathol Vaccinol & Genet Mol, Madrid, Spain. [Guesmi, F.] INSAT, Unite Genie Biol, Tunis 1080, Tunisia. [Kaabi, B.] Inst Pasteur Tunis, Lab Epidemiol & Ecol Parasites, Tunis 1002, Tunisia. [Mejri, M.] Inst Super Etud Technol Zaghouan, Mograne 1121, Tunisia. RP Ahmed, SB (reprint author), Fac Sci Gafsa, Dept Biol, Campus Univ Zarroug Gafsa 2112, Gafsa, Tunisia. EM s_benhadj@yahoo.fr; issam.smaali@insat.rnu.tn RI Ahmed, Sofia/J-7876-2015 FU Ministere de l'Enseignement Superieur, de la Recherche Scientifique et de la Technologie (Tunisia); TMRC NIAID/NIH [15P50A1074178] FX This study was supported by a grant from the Ministere de l'Enseignement Superieur, de la Recherche Scientifique et de la Technologie (Tunisia). RMS and DL were partly supported by a TMRC NIAID/NIH grant (Grant #15P50A1074178). We thank Mr Hamdi Lazhar, Engineer and Director of Bouhedma Natural Park for the identification of the harvested plants used in this study, Dr Chokri Messaoud (INSAT) for his help in the GC-MS analyses and Dr Ghrabi-Gammar Zeineb for the management of specimens, their identification and their deposit in the herbarium of the Laboratory of Medicinal Plants (INAT). NR 32 TC 18 Z9 19 U1 1 U2 14 PU TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXON, ENGLAND SN 1478-6419 J9 NAT PROD RES JI Nat. Prod. Res. PY 2011 VL 25 IS 12 BP 1195 EP 1201 DI 10.1080/14786419.2010.534097 PG 7 WC Chemistry, Applied; Chemistry, Medicinal SC Chemistry; Pharmacology & Pharmacy GA 884EM UT WOS:000299687700010 PM 21740286 ER PT J AU Wagner, W Brenowitz, SD Hammer, JA AF Wagner, Wolfgang Brenowitz, Stephan D. Hammer, John A., III TI Myosin-Va transports the endoplasmic reticulum into the dendritic spines of Purkinje neurons SO NATURE CELL BIOLOGY LA English DT Article ID INOSITOL 1,4,5-TRISPHOSPHATE RECEPTOR; HOMER FAMILY PROTEINS; MELANOSOME TRANSPORT; HIPPOCAMPAL-NEURONS; GLUTAMATE-RECEPTOR; CALCIUM-RELEASE; CEREBELLAR LTD; DILUTE LOCUS; NECK LENGTH; LEVER ARM AB Extension of the endoplasmic reticulum (ER) into dendritic spines of Purkinje neurons is required for cerebellar synaptic plasticity and is disrupted in animals with null mutations in Myo5a, the gene encoding myosin-Va. We show here that myosin-Va acts as a point-to-point organelle transporter to pull ER as cargo into Purkinje neuron spines. Specifically, myosin-Va accumulates at the ER tip as the organelle moves into spines, and hydrolysis of ATP by myosin-Va is required for spine ER targeting. Moreover, myosin-Va is responsible for almost all of the spine ER insertion events. Finally, attenuation of the ability of myosin-Va to move along actin filaments reduces the maximum velocity of ER movement into spines, providing direct evidence that myosin-Va drives ER motility. Thus, we have established that an actin-based motor moves ER within animal cells, and have uncovered the mechanism for ER localization to Purkinje neuron spines, a prerequisite for synaptic plasticity. C1 [Wagner, Wolfgang; Hammer, John A., III] NHLBI, Cell Biol Lab, NIH, Bethesda, MD 20892 USA. [Brenowitz, Stephan D.] Natl Inst Deafness & Other Commun Disorders, Sect Synapt Transmiss, NIH, Bethesda, MD 20892 USA. RP Hammer, JA (reprint author), NHLBI, Cell Biol Lab, NIH, Bethesda, MD 20892 USA. EM hammerj@nhlbi.nih.gov FU Intramural NIH HHS [Z01 DC000072-01] NR 63 TC 77 Z9 78 U1 1 U2 17 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1465-7392 J9 NAT CELL BIOL JI Nat. Cell Biol. PD JAN PY 2011 VL 13 IS 1 BP 40 EP U101 DI 10.1038/ncb2132 PG 19 WC Cell Biology SC Cell Biology GA 697GV UT WOS:000285502200009 PM 21151132 ER PT J AU Purdue, MP Johansson, M Zelenika, D Toro, JR Scelo, G Moore, LE Prokhortchouk, E Wu, XF Kiemeney, LA Gaborieau, V Jacobs, KB Chow, WH Zaridze, D Matveev, V Lubinski, J Trubicka, J Szeszenia-Dabrowska, N Lissowska, J Rudnai, P Fabianova, E Bucur, A Bencko, V Foretova, L Janout, V Boffetta, P Colt, JS Davis, FG Schwartz, KL Banks, RE Selby, PJ Harnden, P Berg, CD Hsing, AW Grubb, RL Boeing, H Vineis, P Clavel-Chapelon, F Palli, D Tumino, R Krogh, V Panico, S Duell, EJ Quiros, JR Sanchez, MJ Navarro, C Ardanaz, E Dorronsoro, M Khaw, KT Allen, NE Bueno-De-Mesquita, HB Peeters, PHM Trichopoulos, D Linseisen, J Ljungberg, B Overvad, K Tjonneland, A Romieu, I Riboli, E Mukeria, A Shangina, O Stevens, VL Thun, MJ Diver, WR Gapstur, SM Pharoah, PD Easton, DF Albanes, D Weinstein, SJ Virtamo, J Vatten, L Hveem, K Njolstad, I Tell, GS Stoltenberg, C Kumar, R Koppova, K Cussenot, O Benhamou, S Oosterwijk, E Vermeulen, SH Aben, KKH van der Marel, SL Ye, YQ Wood, CG Pu, X Mazur, AM Boulygina, ES Chekanov, NN Foglio, M Lechner, D Gut, I Heath, S Blanche, H Hutchinson, A Thomas, G Wang, ZM Yeager, M Fraumeni, JF Skryabin, KG McKay, JD Rothman, N Chanock, SJ Lathrop, M Brennan, P AF Purdue, Mark P. Johansson, Mattias Zelenika, Diana Toro, Jorge R. Scelo, Ghislaine Moore, Lee E. Prokhortchouk, Egor Wu, Xifeng Kiemeney, Lambertus A. Gaborieau, Valerie Jacobs, Kevin B. Chow, Wong-Ho Zaridze, David Matveev, Vsevolod Lubinski, Jan Trubicka, Joanna Szeszenia-Dabrowska, Neonila Lissowska, Jolanta Rudnai, Peter Fabianova, Eleonora Bucur, Alexandru Bencko, Vladimir Foretova, Lenka Janout, Vladimir Boffetta, Paolo Colt, Joanne S. Davis, Faith G. Schwartz, Kendra L. Banks, Rosamonde E. Selby, Peter J. Harnden, Patricia Berg, Christine D. Hsing, Ann W. Grubb, Robert L., III Boeing, Heiner Vineis, Paolo Clavel-Chapelon, Francoise Palli, Domenico Tumino, Rosario Krogh, Vittorio Panico, Salvatore Duell, Eric J. Quiros, Jose Ramon Sanchez, Maria-Jose Navarro, Carmen Ardanaz, Eva Dorronsoro, Miren Khaw, Kay-Tee Allen, Naomi E. Bueno-de-Mesquita, H. Bas Peeters, Petra H. M. Trichopoulos, Dimitrios Linseisen, Jakob Ljungberg, Borje Overvad, Kim Tjonneland, Anne Romieu, Isabelle Riboli, Elio Mukeria, Anush Shangina, Oxana Stevens, Victoria L. Thun, Michael J. Diver, W. Ryan Gapstur, Susan M. Pharoah, Paul D. Easton, Douglas F. Albanes, Demetrius Weinstein, Stephanie J. Virtamo, Jarmo Vatten, Lars Hveem, Kristian Njolstad, Inger Tell, Grethe S. Stoltenberg, Camilla Kumar, Rajiv Koppova, Kvetoslava Cussenot, Olivier Benhamou, Simone Oosterwijk, Egbert Vermeulen, Sita H. Aben, Katja K. H. van der Marel, Saskia L. Ye, Yuanqing Wood, Christopher G. Pu, Xia Mazur, Alexander M. Boulygina, Eugenia S. Chekanov, Nikolai N. Foglio, Mario Lechner, Doris Gut, Ivo Heath, Simon Blanche, Helene Hutchinson, Amy Thomas, Gilles Wang, Zhaoming Yeager, Meredith Fraumeni, Joseph F., Jr. Skryabin, Konstantin G. McKay, James D. Rothman, Nathaniel Chanock, Stephen J. Lathrop, Mark Brennan, Paul TI Genome-wide association study of renal cell carcinoma identifies two susceptibility loci on 2p21 and 11q13.3 SO NATURE GENETICS LA English DT Article ID DENSITY-LIPOPROTEIN HDL; KIDNEY CANCER; PROSTATE-CANCER; FAMILY-HISTORY; PANCREATIC-CANCER; BREAST-CANCER; RISK; TRANSCRIPTION; EPIDEMIOLOGY; CHOLESTEROL AB We conducted a two-stage genome-wide association study of renal cell carcinoma (RCC) in 3,772 affected individuals (cases) and 8,505 controls of European background from 11 studies and followed up 6 SNPs in 3 replication studies of 2,198 cases and 4,918 controls. Two loci on the regions of 2p21 and 11q13.3 were associated with RCC susceptibility below genome-wide significance. Two correlated variants (r(2) = 0.99 in controls), rs11894252 (P = 1.8 x 10(-8)) and rs7579899 (P = 2.3 x 10(-9)), map to EPAS1 on 2p21, which encodes hypoxia-inducible-factor-2 alpha, a transcription factor previously implicated in RCC. The second locus, rs7105934, at 11q13.3, contains no characterized genes (P = 7.8 x 10(-14)). In addition, we observed a promising association on 12q24.31 for rs4765623, which maps to SCARB1, the scavenger receptor class B, member 1 gene (P = 2.6 x 10(-8)). Our study reports previously unidentified genomic regions associated with RCC risk that may lead to new etiological insights. C1 [Purdue, Mark P.; Toro, Jorge R.; Moore, Lee E.; Jacobs, Kevin B.; Chow, Wong-Ho; Colt, Joanne S.; Hsing, Ann W.; Albanes, Demetrius; Weinstein, Stephanie J.; Hutchinson, Amy; Thomas, Gilles; Wang, Zhaoming; Yeager, Meredith; Fraumeni, Joseph F., Jr.; Rothman, Nathaniel; Chanock, Stephen J.] NCI, Div Canc Epidemiol & Genet, NIH, US Dept HHS, Bethesda, MD 20892 USA. [Johansson, Mattias; Scelo, Ghislaine; Gaborieau, Valerie; Romieu, Isabelle; McKay, James D.; Brennan, Paul] Int Agcy Res Canc, F-69372 Lyon, France. [Zelenika, Diana; Foglio, Mario; Lechner, Doris; Gut, Ivo; Heath, Simon; Lathrop, Mark] Ctr Natl Genotypage, Inst Genom, CEA, Evry, France. [Prokhortchouk, Egor; Mazur, Alexander M.; Chekanov, Nikolai N.; Skryabin, Konstantin G.] Russian Acad Sci, Ctr Bioengn, Moscow, Russia. [Prokhortchouk, Egor; Mazur, Alexander M.; Boulygina, Eugenia S.; Skryabin, Konstantin G.] Kurchatov Sci Ctr, Moscow, Russia. [Wu, Xifeng; Ye, Yuanqing; Pu, Xia] Univ Texas MD Anderson Canc Ctr, Dept Epidemiol, Div Canc Prevent & Populat Sci, Houston, TX 77030 USA. [Kiemeney, Lambertus A.; Vermeulen, Sita H.; Aben, Katja K. H.] Radboud Univ Nijmegen, Med Ctr, Dept Epidemiol Biostat & Hlth Technol Assessment, NL-6525 ED Nijmegen, Netherlands. [Kiemeney, Lambertus A.; Oosterwijk, Egbert] Radboud Univ Nijmegen, Med Ctr, Dept Urol, NL-6525 ED Nijmegen, Netherlands. [Jacobs, Kevin B.; Hutchinson, Amy; Thomas, Gilles; Wang, Zhaoming; Yeager, Meredith] NCI, Core Genotyping Facil, SAIC Frederick Inc, Frederick, MD 21701 USA. [Zaridze, David; Matveev, Vsevolod; Mukeria, Anush; Shangina, Oxana] Russian NN Blokhin Canc Res Ctr, Moscow, Russia. [Lubinski, Jan; Trubicka, Joanna] Pomeranian Med Univ, Dept Genet & Pathomorphol, Int Hereditary Canc Ctr, Szczecin, Poland. [Szeszenia-Dabrowska, Neonila] Inst Occupat Med, Dept Epidemiol, Lodz, Poland. [Lissowska, Jolanta] Maria Sklodowska Curie Mem Canc Ctr, Warsaw, Poland. [Lissowska, Jolanta] Inst Oncol, Warsaw, Poland. [Rudnai, Peter] Natl Inst Environm Hlth, Dept Environm Epidemiol, Budapest, Hungary. [Fabianova, Eleonora] Reg Author Publ Hlth, Banska Bystrica, Slovakia. [Bucur, Alexandru] Inst Publ Hlth, Bucharest, Romania. [Bencko, Vladimir] Charles Univ Prague, Fac Med 1, Inst Hyg & Epidemiol, Prague, Czech Republic. [Foretova, Lenka] Masaryk Mem Canc Inst, Dept Canc Epidemiol & Genet, Brno, Czech Republic. [Janout, Vladimir] Palacky Univ, CR-77147 Olomouc, Czech Republic. [Boffetta, Paolo] Mt Sinai Sch Med, Tisch Canc Inst, New York, NY USA. [Davis, Faith G.] Univ Illinois, Sch Publ Hlth, Div Epidemiol & Biostat, Chicago, IL USA. [Schwartz, Kendra L.] Wayne State Univ, Karmanos Canc Inst, Detroit, MI USA. [Schwartz, Kendra L.] Wayne State Univ, Dept Family Med, Detroit, MI USA. [Banks, Rosamonde E.; Selby, Peter J.] St James Univ Hosp, Leeds Inst Mol Med, Canc Res UK Ctr, Leeds, W Yorkshire, England. [Harnden, Patricia] St James Univ Hosp, Dept Pathol, Leeds, W Yorkshire, England. [Berg, Christine D.] NCI, Canc Prevent Div, NIH, US Dept HHS, Bethesda, MD 20892 USA. [Grubb, Robert L., III] Washington Univ, Sch Med, Div Urol Surg, St Louis, MO 63110 USA. [Boeing, Heiner] German Inst Human Nutr, Dept Epidemiol, Potsdam, Nuthetal, Germany. [Vineis, Paolo; Peeters, Petra H. M.; Riboli, Elio] Univ London Imperial Coll Sci Technol & Med, Sch Publ Hlth, London, England. [Vineis, Paolo] Univ London Imperial Coll Sci Technol & Med, Ctr Environm & Hlth, MRC HPA, London, England. [Vineis, Paolo] Human Genet Fdn HuGeF, Turin, Italy. [Clavel-Chapelon, Francoise] Inst Gustave Roussy, Ctr Res Epidemiol & Populat Hlth, INSERM, Villejuif, France. [Clavel-Chapelon, Francoise] Paris S Univ, UMRS 1018, Villejuif, France. [Palli, Domenico] Canc Res & Prevent Inst ISPO, Mol & Nutr Epidemiol Unit, Florence, Italy. [Tumino, Rosario] Azienda Osped Civile MP Arezzo, Canc Registry, Ragusa, Italy. [Krogh, Vittorio] Ist Nazl Tumori, Fdn Ist Ricovero & Cura Carattere Sci IRCCS, Nutr Epidemiol Unit, I-20133 Milan, Italy. [Panico, Salvatore] Univ Naples Federico 2, Dept Clin & Expt Med, Naples, Italy. [Duell, Eric J.] Catalan Inst Oncol ICO IDIBELL, Canc Epidemiol Res Program, Unit Nutr Environm & Canc, Barcelona, Spain. [Quiros, Jose Ramon] Consejeria Serv Sociales, Jefe Secc Informac Sanitaria, Oviedo, Spain. [Sanchez, Maria-Jose] Andalusian Sch Publ Hlth, Granada, Spain. [Sanchez, Maria-Jose; Navarro, Carmen; Ardanaz, Eva; Dorronsoro, Miren] CIBER Epidemiol & Salud Publ CIBERESP, Barcelona, Spain. [Navarro, Carmen] Reg Council Hlth & Consumer Affairs, Dept Epidemiol, Murcia, Spain. [Ardanaz, Eva] Publ Hlth Inst Navarra, Pamplona, Spain. [Dorronsoro, Miren] Basque Reg Hlth Dept, Publ Hlth Div Gipuzkoa, San Sebastian, Spain. [Khaw, Kay-Tee] Univ Cambridge, Dept Publ Hlth & Primary Care, Dept Gerontol, Cambridge, England. [Allen, Naomi E.] Univ Oxford, Nuffield Dept Clin Med, Canc Epidemiol Unit, Oxford, England. [Bueno-de-Mesquita, H. Bas] Natl Inst Publ Hlth & Environm RIVM, Bilthoven, Netherlands. [Peeters, Petra H. M.] Univ Med Ctr, Julius Ctr Hlth Sci & Primary Care, Utrecht, Netherlands. [Trichopoulos, Dimitrios] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. [Trichopoulos, Dimitrios] Acad Athens, Bur Epidemiol Res, Athens, Greece. [Linseisen, Jakob] German Canc Res Ctr, Div Canc Epidemiol, D-6900 Heidelberg, Germany. [Linseisen, Jakob] Helmholtz Ctr Munich, Inst Epidemiol, Munich, Germany. [Ljungberg, Borje] Umea Univ, Dept Surg & Perioperat Sci Urol & Androl, Umea, Sweden. [Overvad, Kim; Stevens, Victoria L.; Diver, W. Ryan] Aarhus Univ, Sch Publ Hlth, Dept Epidemiol, Aarhus, Denmark. [Tjonneland, Anne] Inst Canc Epidemiol, Danish Canc Soc, Copenhagen, Denmark. [Thun, Michael J.; Gapstur, Susan M.] Amer Canc Soc, Epidemiol Res Program, Atlanta, GA 30329 USA. [Pharoah, Paul D.; Easton, Douglas F.] Univ Cambridge, Dept Oncol, Cambridge, England. [Pharoah, Paul D.; Easton, Douglas F.] Univ Cambridge, Dept Publ Hlth & Primary Care, Cambridge, England. [Virtamo, Jarmo] Natl Inst Hlth & Welf, Dept Chron Dis Prevent, Helsinki, Finland. [Vatten, Lars; Hveem, Kristian] Norwegian Univ Sci & Technol, Fac Med, Dept Publ Hlth, N-7034 Trondheim, Norway. [Njolstad, Inger] Univ Tromso, Dept Community Med, Tromso, Norway. [Tell, Grethe S.] Univ Bergen, Dept Publ Hlth & Primary Hlth Care, Bergen, Norway. [Stoltenberg, Camilla] Norwegian Inst Publ Hlth, Div Epidemiol, Oslo, Norway. [Kumar, Rajiv] German Canc Res Ctr, Div Mol Genet Epidemiol, D-6900 Heidelberg, Germany. [Koppova, Kvetoslava] Reg Author Publ Hlth, Dept Environm Hyg, Banska Bystrica, Slovakia. [Cussenot, Olivier] Univ Paris 06, Tenon Hosp, APHP, CeRePP,ER2, Paris, France. [Benhamou, Simone] Fdn Jean Dausset, Ctr Etud Polymorphisme Humain, INSERM, U946, Paris, France. [Benhamou, Simone] Inst Gustave Roussy, CNRS, UMR8200, Villejuif, France. [Vermeulen, Sita H.; van der Marel, Saskia L.] Radboud Univ Nijmegen, Med Ctr, Dept Human Genet, NL-6525 ED Nijmegen, Netherlands. [Aben, Katja K. H.] Comprehens Canc Ctr E, Dept Canc Registry & Res, Nijmegen, Netherlands. [Wood, Christopher G.] Univ Texas MD Anderson Canc Ctr, Dept Urol, Houston, TX 77030 USA. RP Chanock, SJ (reprint author), NCI, Div Canc Epidemiol & Genet, NIH, US Dept HHS, Bethesda, MD 20892 USA. EM chanocks@mail.nih.gov; brennan@iarc.fr RI Tell, Grethe/G-5639-2015; Purdue, Mark/C-9228-2016; Vermeulen, H.H.M./L-4716-2015; Aben, Katja/G-9686-2016; Prokhortchouk, Egor/I-9108-2014; Benhamou, Simone/K-6554-2015; Krogh, Vittorio/K-2628-2016; Panico, Salvatore/K-6506-2016; Kiemeney, Lambertus/D-3357-2009; Clavel-Chapelon, Francoise/G-6733-2014; Berg , Christine/K-1047-2014; Janout, Vladimir/M-5133-2014; Oosterwijk, Egbert/P-5466-2014; SANCHEZ-PEREZ, MARIA JOSE/D-1087-2011; Szeszenia-Dabrowska, Neonila/F-7190-2010; Pu, Xia/H-2670-2012; Heath, Simon/J-4138-2012; Zaridze, David/K-5605-2013; Linseisen, Jakob/B-5353-2014; Albanes, Demetrius/B-9749-2015; OI Tell, Grethe/0000-0003-1386-1638; Purdue, Mark/0000-0003-1177-3108; Aben, Katja/0000-0002-0214-2147; Krogh, Vittorio/0000-0003-0122-8624; Panico, Salvatore/0000-0002-5498-8312; Chekanov, Nikolay/0000-0003-1131-3195; Kumar, Rajiv/0000-0002-6093-0395; Duell, Eric J/0000-0001-5256-0163; Kiemeney, Lambertus/0000-0002-2368-1326; SANCHEZ-PEREZ, MARIA JOSE/0000-0003-4817-0757; Linseisen, Jakob/0000-0002-9386-382X; Lissowska, Jolanta/0000-0003-2695-5799; Banks, Rosamonde/0000-0002-0042-8715; PALLI, Domenico/0000-0002-5558-2437 FU French Institut National du Cancer (INCa); National Cancer Institute (NCI), US National Institutes of Health (NIH) FX The authors thank all of the participants who took part in this research and the funders and support staff who made this study possible. Funding for the genome-wide genotyping was provided by the French Institut National du Cancer (INCa) for those studies coordinated by IARC/CNG, and by the intramural research program of the National Cancer Institute (NCI), US National Institutes of Health (NIH) for those studies coordinated by the NCI. Additional acknowledgments can be found in the Supplementary Note. NR 37 TC 112 Z9 117 U1 3 U2 32 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1061-4036 J9 NAT GENET JI Nature Genet. PD JAN PY 2011 VL 43 IS 1 BP 60 EP U83 DI 10.1038/ng.723 PG 8 WC Genetics & Heredity SC Genetics & Heredity GA 699SQ UT WOS:000285683500017 PM 21131975 ER PT J AU Yamane, A Resch, W Kuo, N Kuchen, S Li, ZY Sun, HW Robbiani, DF McBride, K Nussenzweig, MC Casellas, R AF Yamane, Arito Resch, Wolfgang Kuo, Nan Kuchen, Stefan Li, Zhiyu Sun, Hong-wei Robbiani, Davide F. McBride, Kevin Nussenzweig, Michel C. Casellas, Rafael TI Deep-sequencing identification of the genomic targets of the cytidine deaminase AID and its cofactor RPA in B lymphocytes SO NATURE IMMUNOLOGY LA English DT Article ID CLASS-SWITCH RECOMBINATION; RNA-POLYMERASE-II; ACTIVATION-INDUCED DEAMINASE; REPLICATION PROTEIN-A; SOMATIC HYPERMUTATION; C-MYC; IMMUNOGLOBULIN GENES; CELL LYMPHOMAS; KINASE-A; IG GENES AB The cytidine deaminase AID hypermutates immunoglobulin genes but can also target oncogenes, leading to tumorigenesis. The extent of AID's promiscuity and its predilection for immunoglobulin genes are unknown. We report here that AID interacted broadly with promoter-proximal sequences associated with stalled polymerases and chromatin-activating marks. In contrast, genomic occupancy of replication protein A (RPA), an AID cofactor, was restricted to immunoglobulin genes. The recruitment of RPA to the immunoglobulin loci was facilitated by phosphorylation of AID at Ser38 and Thr140. We propose that stalled polymerases recruit AID, thereby resulting in low frequencies of hypermutation across the B cell genome. Efficient hypermutation and switch recombination required AID phosphorylation and correlated with recruitment of RPA. Our findings provide a rationale for the oncogenic role of AID in B cell malignancy. C1 [Robbiani, Davide F.; McBride, Kevin; Nussenzweig, Michel C.] Rockefeller Univ, Howard Hughes Med Inst, Lab Mol Immunol, New York, NY 10021 USA. [Yamane, Arito; Resch, Wolfgang; Kuo, Nan; Kuchen, Stefan; Li, Zhiyu; Sun, Hong-wei; Casellas, Rafael] NIAMSD, NIH, Bethesda, MD 20892 USA. [Casellas, Rafael] NCI, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. RP Nussenzweig, MC (reprint author), Rockefeller Univ, Howard Hughes Med Inst, Lab Mol Immunol, New York, NY 10021 USA. EM nussen@mail.rockefeller.edu; casellar@mail.nih.gov RI mcbride, kevin/E-8230-2011; Yamane, Arito/A-2959-2013; OI Kuchen, Stefan/0000-0003-4899-8132 FU National Institutes of Health (National Institute of Arthritis and Musculoskeletal and Skin Diseases) [AI037526]; Howard Hughes Medical Institute FX We thank D. Schatz for comments on the manuscript; J. Chaudhuri (Memorial Sloan-Kettering Cancer Center) and F. Alt (Harvard University) for antibodies to AID; J. Simone for cell sorting; G. Gutierrez for technical assistance with the genome analyzer; and C. Ansarah-Sobrinho and S. Nelson for help with sequencing. Supported by the National Institutes of Health (Intramural Research Program of the National Institute of Arthritis and Musculoskeletal and Skin Diseases; and AI037526 to M.C.N.) and the Howard Hughes Medical Institute (M.C.N.). NR 50 TC 147 Z9 150 U1 0 U2 8 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1529-2908 J9 NAT IMMUNOL JI Nat. Immunol. PD JAN PY 2011 VL 12 IS 1 BP 62 EP U85 DI 10.1038/ni.1964 PG 9 WC Immunology SC Immunology GA 696TU UT WOS:000285465100014 PM 21113164 ER PT J AU Maul, RW Saribasak, H Martomo, SA McClure, RL Yang, W Vaisman, A Gramlich, HS Schatz, DG Woodgate, R Wilson, DM Gearhart, PJ AF Maul, Robert W. Saribasak, Huseyin Martomo, Stella A. McClure, Rhonda L. Yang, William Vaisman, Alexandra Gramlich, Hillary S. Schatz, David G. Woodgate, Roger Wilson, David M., III Gearhart, Patricia J. TI Uracil residues dependent on the deaminase AID in immunoglobulin gene variable and switch regions SO NATURE IMMUNOLOGY LA English DT Article ID INDUCED CYTIDINE DEAMINASE; SINGLE-STRANDED-DNA; LIGHT-CHAIN GENE; SOMATIC HYPERMUTATION; B-CELLS; ANTIBODY DIVERSIFICATION; GLYCOSYLASE ACTIVITY; R-LOOPS; RECOMBINATION; MICE AB Activation-induced deaminase (AID) initiates diversity of immunoglobulin genes through deamination of cytosine to uracil. Two opposing models have been proposed for the deamination of DNA or RNA by AID. Although most data support DNA deamination, there is no physical evidence of uracil residues in immunoglobulin genes. Here we demonstrate their presence by determining the sensitivity of DNA to digestion with uracil DNA glycosylase (UNG) and abasic endonuclease. Using several methods of detection, we identified uracil residues in the variable and switch regions. Uracil residues were generated within 24 h of B cell stimulation, were present on both DNA strands and were found to replace mainly cytosine bases. Our data provide direct evidence for the model that AID functions by deaminating cytosine residues in DNA. C1 [Maul, Robert W.; Saribasak, Huseyin; Martomo, Stella A.; McClure, Rhonda L.; Yang, William; Wilson, David M., III; Gearhart, Patricia J.] NIA, Lab Mol Gerontol, NIH, Baltimore, MD 21224 USA. [Vaisman, Alexandra; Woodgate, Roger] NICHHD, Lab Genom Integr, NIH, Bethesda, MD 20892 USA. [Gramlich, Hillary S.] Yale Univ, Sch Med, Howard Hughes Med Inst, Dept Cell Biol, New Haven, CT 06510 USA. [Schatz, David G.] Yale Univ, Sch Med, Howard Hughes Med Inst, Dept Immunol, New Haven, CT 06510 USA. RP Gearhart, PJ (reprint author), NIA, Lab Mol Gerontol, NIH, Baltimore, MD 21224 USA. EM gearhartp@mail.nih.gov RI Saribasak, Huseyin/C-9331-2012; Schatz, David/A-6748-2013; Vaisman, Alexandra/C-3766-2013; OI Saribasak, Huseyin/0000-0003-0055-062X; Schatz, David/0000-0002-5669-1176; Vaisman, Alexandra/0000-0002-2521-1467; Maul, Robert/0000-0002-6958-8514 FU Howard Hughes Medical Institute; National Institute on Aging; National Institute of Child Health and Human Development of the National Institutes of Health FX We thank J. Stivers (John Hopkins University) for UNG; S. Wilson (National Institute of Environmental Health Sciences, National Institutes of Health) for polymerase beta-lyase; R. Kohli (University of Pennsylvania), J. Buerstedde and H. Arakawa (Max Planck Institute of Biochemistry) for reagents and advice; S. Fugmann and R. Sen for discussions; T. Wolf, C. Nguyen and R. Wersto for assistance in flow cytometry; and the Comparative Medicine Section for mouse maintenance. Supported by the National Institute on Aging and the National Institute of Child Health and Human Development of the National Institutes of Health (Intramural Research Program) and Howard Hughes Medical Institute (D.G.S.). NR 55 TC 65 Z9 65 U1 2 U2 3 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1529-2908 J9 NAT IMMUNOL JI Nat. Immunol. PD JAN PY 2011 VL 12 IS 1 BP 70 EP U93 DI 10.1038/ni.1970 PG 8 WC Immunology SC Immunology GA 696TU UT WOS:000285465100015 PM 21151102 ER PT J AU Maruyama, T Li, J Vaque, JP Konkel, JE Wang, WF Zhang, BJ Zhang, P Zamarron, BF Yu, DY Wu, YT Zhuang, YA Gutkind, JS Chen, WJ AF Maruyama, Takashi Li, Jun Vaque, Jose P. Konkel, Joanne E. Wang, Weifeng Zhang, Baojun Zhang, Pin Zamarron, Brian F. Yu, Dongyang Wu, Yuntao Zhuang, Yuan Gutkind, J. Silvio Chen, WanJun TI Control of the differentiation of regulatory T cells and T(H)17 cells by the DNA-binding inhibitor Id3 SO NATURE IMMUNOLOGY LA English DT Article ID TRANSCRIPTION FACTOR FOXP3; ROR-GAMMA-T; GROWTH-FACTOR-BETA; TGF-BETA; CD3-SPECIFIC ANTIBODY; GENE-EXPRESSION; TOLERANCE; PROTEINS; RECEPTOR; LINEAGE AB The molecular mechanisms that direct transcription of the gene encoding the transcription factor Foxp3 in CD4(+) T cells remain ill-defined. We show here that deletion of the DNA-binding inhibitor Id3 resulted in the defective generation of Foxp3(+) regulatory T cells (T-reg cells). We identify two transforming growth factor-beta 1 (TGF-beta 1)-dependent mechanisms that were vital for activation of Foxp3 transcription and were defective in Id3(-/-) CD4(+) T cells. Enhanced binding of the transcription factor E2A to the Foxp3 promoter promoted Foxp3 transcription. Id3 was required for relief of inhibition by the transcription factor GATA-3 at the Foxp3 promoter. Furthermore, Id3(-/-) T cells showed greater differentiation into the T(H)17 subset of helper T cells in vitro and in a mouse asthma model. Therefore, a network of factors acts in a TGF-beta-dependent manner to control Foxp3 expression and inhibit the development of T(H)17 cells. C1 [Maruyama, Takashi; Li, Jun; Konkel, Joanne E.; Zhang, Pin; Zamarron, Brian F.; Chen, WanJun] Natl Inst Dent & Craniofacial Res, Mucosal Immunol Unit, Oral Infect & Immun Branch, NIH, Bethesda, MD USA. [Vaque, Jose P.; Gutkind, J. Silvio] Natl Inst Dent & Craniofacial Res, Oral Pharyngeal Canc Branch, NIH, Bethesda, MD USA. [Wang, Weifeng; Yu, Dongyang; Wu, Yuntao] George Mason Univ, Dept Microbiol & Mol Biol, Manassas, VA USA. [Zhang, Baojun; Zhuang, Yuan] Duke Univ, Dept Immunol, Durham, NC USA. RP Chen, WJ (reprint author), Natl Inst Dent & Craniofacial Res, Mucosal Immunol Unit, Oral Infect & Immun Branch, NIH, Bethesda, MD USA. EM wchen@dir.nidcr.nih.gov RI Gutkind, J. Silvio/A-1053-2009; wang, weifeng/N-4140-2013; ZHANG, BAOJUN/N-3863-2014; MaruYama, Takashi/N-5994-2014; Li, Jun/N-6267-2015; Vaque, Jose/H-8413-2015; OI ZHANG, BAOJUN/0000-0002-7786-4304; Vaque, Jose/0000-0002-3913-2495; Zamarron, Brian/0000-0001-6549-4230 FU National Institute of Dental and Craniofacial Research (US National Institutes of Health) FX We thank Y.H. Chen, Q. Ruan and M. Tone (University of Pennsylvania) for Foxp3 constructs and EL4 LAF cells. Supported by the Intramural Research Program of the National Institute of Dental and Craniofacial Research (US National Institutes of Health). NR 49 TC 71 Z9 74 U1 2 U2 11 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1529-2908 J9 NAT IMMUNOL JI Nat. Immunol. PD JAN PY 2011 VL 12 IS 1 BP 86 EP U114 DI 10.1038/ni.1965 PG 11 WC Immunology SC Immunology GA 696TU UT WOS:000285465100017 PM 21131965 ER PT J AU Vaegter, CB Jansen, P Fjorback, AW Glerup, S Skeldal, S Kjolby, M Richner, M Erdmann, B Nyengaard, JR Tessarollo, L Lewin, GR Willnow, TE Chao, MV Nykjaer, A AF Vaegter, Christian B. Jansen, Pernille Fjorback, Anja W. Glerup, Simon Skeldal, Sune Kjolby, Mads Richner, Mette Erdmann, Bettina Nyengaard, Jens R. Tessarollo, Lino Lewin, Gary R. Willnow, Thomas E. Chao, Moses V. Nykjaer, Anders TI Sortilin associates with Trk receptors to enhance anterograde transport and neurotrophin signaling SO NATURE NEUROSCIENCE LA English DT Article ID DORSAL-ROOT GANGLION; SENSORY NEURONS; NERVOUS-SYSTEM; BIOCHEMICAL-CHARACTERIZATION; TARGETED DISRUPTION; AXONAL-TRANSPORT; MICE LACKING; GENE; PROTEIN; BRAIN AB Binding of target-derived neurotrophins to Trk receptors at nerve terminals is required to stimulate neuronal survival, differentiation, innervation and synaptic plasticity. The distance between the soma and nerve terminal is great, making efficient anterograde Trk transport critical for Trk synaptic translocation and signaling. The mechanism responsible for this trafficking remains poorly understood. Here we show that the sorting receptor sortilin interacts with TrkA, TrkB and TrkC and enables their anterograde axonal transport, thereby enhancing neurotrophin signaling. Cultured DRG neurons lacking sortilin showed blunted MAP kinase signaling and reduced neurite outgrowth upon stimulation with NGF. Moreover, deficiency for sortilin markedly aggravated TrkA, TrkB and TrkC phenotypes present in p75(NTR) knockouts, and resulted in increased embryonic lethality and sympathetic neuropathy in mice heterozygous for TrkA. Our findings demonstrate a role for sortilin as an anterograde trafficking receptor for Trk and a positive modulator of neurotrophin-induced neuronal survival. C1 [Vaegter, Christian B.; Jansen, Pernille; Glerup, Simon; Skeldal, Sune; Kjolby, Mads; Richner, Mette; Nykjaer, Anders] Aarhus Univ, Dept Med Biochem, Lundbeck Fdn, Res Ctr MIND, Aarhus, Denmark. [Fjorback, Anja W.; Nyengaard, Jens R.] Aarhus Univ, Stereol & Electron Microscopy Lab, Lundbeck Fdn, Res Ctr MIND, Aarhus, Denmark. [Erdmann, Bettina; Lewin, Gary R.; Willnow, Thomas E.] Max Delbruck Ctr Mol Med, Berlin, Germany. [Tessarollo, Lino] NCI, Ctr Canc Res, Frederick, MD 21701 USA. [Chao, Moses V.] NYU, Sch Med, Skirball Inst Biomol Med, Kimmel Ctr, New York, NY USA. RP Nykjaer, A (reprint author), Aarhus Univ, Dept Med Biochem, Lundbeck Fdn, Res Ctr MIND, Aarhus, Denmark. EM cv@biokemi.au.dk; an@biokemi.au.dk RI Vaegter, Christian/A-7909-2008; Kjolby, Mads/F-3672-2011; OI Vaegter, Christian/0000-0001-6573-146X; Nykjaer, Anders/0000-0001-6422-6736; Kjolby, Mads/0000-0002-1043-6137; Chao, Moses/0000-0002-6969-3744; Lewin, Gary/0000-0002-2890-6352 FU Lundbeck Foundation; Danish Medical Research Council; Elvira and Rasmus Rissforts Foundation; MEMORIES (European Union); US National Institutes of Health [NS21072, AG025970, HD23315]; Deutsche Forschungsgemeinschaft; Danish Council for Strategic Research; Center for Stochastic Geometry and Advanced Bioimaging (Villum Foundation) FX We thank L. Reichardt (University of California, San Francisco) for the TrkA antibody. The ImageJ KymoToolBox plug-in was kindly provided by F. Cordelieres (Universite Paris-Sud Orsay), and the NeuriteTracer plug-in by M. Pool (Rue University). This work was supported by the Lundbeck Foundation, The Danish Medical Research Council, Elvira and Rasmus Rissforts Foundation, MEMORIES (European Union, Framework Programme 6), US National Institutes of Health (NS21072, AG025970 and HD23315), the Deutsche Forschungsgemeinschaft, Danish Council for Strategic Research, and Center for Stochastic Geometry and Advanced Bioimaging (Villum Foundation). NR 50 TC 73 Z9 77 U1 4 U2 15 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1097-6256 J9 NAT NEUROSCI JI Nat. Neurosci. PD JAN PY 2011 VL 14 IS 1 BP 54 EP U78 DI 10.1038/nn.2689 PG 10 WC Neurosciences SC Neurosciences & Neurology GA 699TE UT WOS:000285684900014 PM 21102451 ER PT J AU Noskov, VN Chuang, RY Gibson, DG Leem, SH Larionov, V Kouprina, N AF Noskov, Vladimir N. Chuang, Ray-Yuan Gibson, Daniel G. Leem, Sun-Hee Larionov, Vladimir Kouprina, Natalay TI Isolation of circular yeast artificial chromosomes for synthetic biology and functional genomics studies SO NATURE PROTOCOLS LA English DT Article ID TRANSFORMATION-ASSOCIATED RECOMBINATION; MYCOPLASMA-GENITALIUM GENOME; HUMAN DNA; CLONING; GENE; FRAGMENTS; VECTOR; EXPRESSION; CENTROMERE; EVOLUTION AB Circular yeast artificial chromosomes (YACs) provide significant advantages for cloning and manipulating large segments of genomic DNA in Saccharomyces cerevisiae. However, it has been difficult to exploit these advantages, because circular YACs are difficult to isolate and purify. Here we describe a method for purification of large circular YACs that is more reliable compared with previously described protocols. This method has been used to purify YACs up to 600 kb in size. The purified YAC DNA is suitable for restriction enzyme digestion, DNA sequencing and functional studies. For example, YACs carrying full-size genes can be purified from yeast and used for transfection into mammalian cells or for the construction of a synthetic genome that can be used to produce a synthetic cell. This method for isolating high-quality YAC DNA in microgram quantities should be valuable for functional and synthetic genomic studies. The entire protocol takes similar to 3 d to complete. C1 [Leem, Sun-Hee; Larionov, Vladimir; Kouprina, Natalay] NCI, Mol Pharmacol Lab, NIH, Bethesda, MD 20892 USA. [Noskov, Vladimir N.; Chuang, Ray-Yuan; Gibson, Daniel G.] J Craig Venter Inst, Rockville, MD USA. [Leem, Sun-Hee] Dong A Univ, Dept Biol Sci, Pusan, South Korea. RP Kouprina, N (reprint author), NCI, Mol Pharmacol Lab, NIH, Bethesda, MD 20892 USA. EM kouprinn@mail.nih.gov FU Synthetic Genomics (SGI); National Institutes of Health National Cancer Institute, Center for Cancer Research FX The research reported in this article was supported by Synthetic Genomics (SGI) (V.N.N., R.-Y.C. and D.G.G.) and by the intramural research program of the National Institutes of Health National Cancer Institute, Center for Cancer Research (V.L. and N.K.). NR 24 TC 11 Z9 11 U1 2 U2 12 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1754-2189 J9 NAT PROTOC JI Nat. Protoc. PD JAN PY 2011 VL 6 IS 1 BP 89 EP 96 DI 10.1038/nprot.2010.174 PG 8 WC Biochemical Research Methods SC Biochemistry & Molecular Biology GA 703FY UT WOS:000285965000009 PM 21212778 ER PT J AU Fleg, JL Aronow, WS Frishman, WH AF Fleg, Jerome L. Aronow, Wilbert S. Frishman, William H. TI Cardiovascular drug therapy in the elderly: benefits and challenges SO NATURE REVIEWS CARDIOLOGY LA English DT Review ID ACUTE CORONARY SYNDROMES; RANDOMIZED CONTROLLED-TRIAL; CONGESTIVE-HEART-FAILURE; ISOLATED SYSTOLIC HYPERTENSION; LEFT-VENTRICULAR DYSFUNCTION; CONVERTING-ENZYME INHIBITORS; ACUTE MYOCARDIAL-INFARCTION; TYPE-2 DIABETES-MELLITUS; ST-SEGMENT-ELEVATION; END-POINT REDUCTION AB Increasing life expectancy in industrialized societies has resulted in a huge population of older adults with cardiovascular disease. Despite advances in device therapy and surgery, the mainstay of treatment for these disorders remains pharmacological. Hypertension affects two-thirds of older adults and remains a potent risk factor for coronary artery disease, chronic heart failure, atrial fibrillation, and stroke in this age group. Numerous trials have demonstrated reduction in these adverse outcomes with antihypertensive drugs. After acute myocardial infarction, beta-adrenergic blockers reduce mortality regardless of patient age. Statins and antiplatelet drugs have proven beneficial in both primary and, especially, secondary prevention of coronary events in older adults. In elders with chronic heart failure, loop diuretics must be used cautiously, owing to their higher potential for adverse effects, whereas angiotensin-converting-enzyme inhibitors and beta-blockers reduce symptoms and prolong survival. The high risk of stroke in elderly patients with atrial fibrillation is markedly reduced with warfarin, although bleeding risk is increased. The high prevalence of polypharmacy among older adults with cardiovascular disease, coupled with age-associated physiological changes and comorbidities, provides major challenges in adherence and avoidance of drug-related adverse events. C1 [Fleg, Jerome L.] NHLBI, Div Cardiovasc Sci, Bethesda, MD 20892 USA. [Aronow, Wilbert S.; Frishman, William H.] New York Med Coll, Dept Med, Valhalla, NY 10595 USA. RP Fleg, JL (reprint author), NHLBI, Div Cardiovasc Sci, 6701 Rockledge Dr, Bethesda, MD 20892 USA. EM flegj@nhlbi.nih.gov NR 144 TC 44 Z9 45 U1 3 U2 14 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1759-5002 J9 NAT REV CARDIOL JI Nat. Rev. Cardiol. PD JAN PY 2011 VL 8 IS 1 BP 13 EP 28 DI 10.1038/nrcardio.2010.162 PG 16 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 696PI UT WOS:000285453400004 PM 20978470 ER PT J AU Saleh, M Trinchieri, G AF Saleh, Maya Trinchieri, Giorgio TI Innate immune mechanisms of colitis and colitis-associated colorectal cancer SO NATURE REVIEWS IMMUNOLOGY LA English DT Review ID INFLAMMATORY-BOWEL-DISEASE; GENOME-WIDE ASSOCIATION; DEXTRAN SODIUM-SULFATE; INTESTINAL EPITHELIAL-CELLS; DIET-INDUCED OBESITY; T-BET DEFICIENCY; CROHNS-DISEASE; COLON CARCINOGENESIS; ULCERATIVE-COLITIS; DENDRITIC CELLS AB The innate immune system provides first-line defences in response to invading microorganisms and endogenous danger signals by triggering robust inflammatory and antimicrobial responses. However, innate immune sensing of commensal microorganisms in the intestinal tract does not lead to chronic intestinal inflammation in healthy individuals, reflecting the intricacy of the regulatory mechanisms that tame the inflammatory response in the gut. Recent findings suggest that innate immune responses to commensal microorganisms, although once considered to be harmful, are necessary for intestinal homeostasis and immune tolerance. This Review discusses recent findings that identify a crucial role for innate immune effector molecules in protection against colitis and colitis-associated colorectal cancer and the therapeutic implications that ensue. C1 [Saleh, Maya] McGill Univ, Dept Med, Montreal, PQ H3G 0B1, Canada. [Trinchieri, Giorgio] NCI, Canc & Inflammat Program, Ctr Canc Res, Frederick, MD 21702 USA. RP Saleh, M (reprint author), McGill Univ, Dept Med, Montreal, PQ H3G 0B1, Canada. EM maya.saleh@mcgill.ca; trinchig@mail.nih.gov FU Canadian Institutes for Health Research [MOP-79410, MOP-82801, MOP-86546, CTP-87520]; Burroughs Wellcome Fund; US National Institutes of Health, National Cancer Institute, Center for Cancer Research, USA FX M.S. thanks the students and colleagues in her laboratory for reading and commenting on this manuscript. Work in M.S.'s laboratory is supported by the Canadian Institutes for Health Research (MOP-79410, MOP-82801, MOP-86546, CTP-87520) and the Burroughs Wellcome Fund. Work in G.T.'s laboratory is supported by the Intramural Research Program of the US National Institutes of Health, National Cancer Institute, Center for Cancer Research, USA. NR 130 TC 148 Z9 156 U1 8 U2 33 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1474-1733 J9 NAT REV IMMUNOL JI Nat. Rev. Immunol. PD JAN PY 2011 VL 11 IS 1 BP 9 EP 20 DI 10.1038/nri2891 PG 12 WC Immunology SC Immunology GA 698DR UT WOS:000285572600010 PM 21151034 ER PT J AU Balagopalan, L Sherman, E Barr, VA Samelson, LE AF Balagopalan, Lakshmi Sherman, Eilon Barr, Valarie A. Samelson, Lawrence E. TI Imaging techniques for assaying lymphocyte activation in action SO NATURE REVIEWS IMMUNOLOGY LA English DT Review ID T-CELL-RECEPTOR; RESONANCE ENERGY-TRANSFER; IMMUNOLOGICAL SYNAPSE FORMATION; FC-EPSILON-RI; MICROTUBULE-ORGANIZING CENTER; PLASMA-MEMBRANE MICRODOMAINS; NODE B-CELLS; ANTIGEN RECEPTOR; LIPID RAFTS; 2-PHOTON MICROSCOPY AB Imaging techniques have greatly improved our understanding of lymphocyte activation. Technical advances in spatial and temporal resolution and new labelling tools have enabled researchers to directly observe the activation process. Consequently, research using imaging approaches to study lymphocyte activation has expanded, providing an unprecedented level of cellular and molecular detail in the field. As a result, certain models of lymphocyte activation have been verified, others have been revised and yet others have been replaced with new concepts. In this article, we review the current imaging techniques that are used to assess lymphocyte activation in different contexts, from whole animals to single molecules, and discuss the advantages and potential limitations of these methods. C1 [Balagopalan, Lakshmi; Sherman, Eilon; Barr, Valarie A.; Samelson, Lawrence E.] NCI, Lab Cellular & Mol Biol, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. RP Samelson, LE (reprint author), NCI, Lab Cellular & Mol Biol, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. EM samelson@helix.nih.gov RI Sherman, Eilon /B-3688-2014 OI Sherman, Eilon /0000-0002-7403-6036 FU National Institutes of Health (NIH), National Cancer Institute (NCI), Center for Cancer Research (CCR) FX We thank R. Kortum for critically reading the manuscript. This research was supported by the Intramural Research Program of the National Institutes of Health (NIH), National Cancer Institute (NCI), Center for Cancer Research (CCR). NR 129 TC 36 Z9 36 U1 1 U2 17 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1474-1733 J9 NAT REV IMMUNOL JI Nat. Rev. Immunol. PD JAN PY 2011 VL 11 IS 1 BP 21 EP 33 DI 10.1038/nri2903 PG 13 WC Immunology SC Immunology GA 698DR UT WOS:000285572600011 PM 21179118 ER PT J AU Koup, RA Graham, BS Douek, DC AF Koup, Richard A. Graham, Barney S. Douek, Daniel C. TI The quest for a T cell-based immune correlate of protection against HIV: a story of trials and errors SO NATURE REVIEWS IMMUNOLOGY LA English DT Article ID IMMUNODEFICIENCY-VIRUS TYPE-1; VACCINE-INDUCED IMMUNITY; VIRAL SET-POINT; ESCAPE MUTATIONS; CLASS-I; DISEASE PROGRESSION; EPITOPE VARIANTS; CLINICAL-TRIALS; RHESUS MACAQUES; DOUBLE-BLIND AB Even before the partial success of a preventive HIV vaccine in a recent Phase III clinical trial, there had been an active research effort to determine one or more immune correlates of protection for HIV infection. This effort has been hampered by the lack of natural protective immunity against HIV. As a result, most of the studies have focused on long-term non-progressive infection or other clinical situations, none of which fully recapitulates protective immunity against HIV. Although this effort has been successful in defining characteristics of T cells in acute and non-progressive HIV infection, and has therefore greatly expanded our knowledge of the immunopathogenesis of AIDS, its success in defining immune correlates of protection is less clear. In this Opinion article we offer a perspective on how successful this effort has been in defining immune correlates of protection that have been, or will be, of use in the development of an HIV vaccine. Our view is that investing in an iterative approach to human vaccine efficacy trials of sufficient size and sampling frequency will improve the likelihood that an immune correlate of vaccine protection will be defined. C1 [Koup, Richard A.; Graham, Barney S.; Douek, Daniel C.] NIAID, Vaccine Res Ctr, NIH, Bethesda, MD 20892 USA. RP Douek, DC (reprint author), NIAID, Vaccine Res Ctr, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA. EM ddouek@mail.nih.gov NR 70 TC 26 Z9 26 U1 1 U2 8 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1474-1733 J9 NAT REV IMMUNOL JI Nat. Rev. Immunol. PD JAN PY 2011 VL 11 IS 1 BP 65 EP 70 DI 10.1038/nri2890 PG 6 WC Immunology SC Immunology GA 698DR UT WOS:000285572600015 PM 21164527 ER PT J AU Youle, RJ Narendra, DP AF Youle, Richard J. Narendra, Derek P. TI Mechanisms of mitophagy SO NATURE REVIEWS MOLECULAR CELL BIOLOGY LA English DT Review ID MITOCHONDRIAL-DNA DELETIONS; RECESSIVE JUVENILE PARKINSONISM; SUBSTANTIA-NIGRA NEURONS; RETICULOCYTE MATURATION; PINK1/PARKIN-MEDIATED MITOPHAGY; AUTOPHAGOSOME BIOGENESIS; ERYTHROID-CELLS; PINK1; DISEASE; MUTATIONS AB Autophagy not only recycles intracellular components to compensate for nutrient deprivation but also selectively eliminates organelles to regulate their number and maintain quality control. Mitophagy, the specific autophagic elimination of mitochondria, has been identified in yeast, mediated by autophagy-related 32 (Atg32), and in mammals during red blood cell differentiation, mediated by NIP3-like protein X (NIX; also known as BNIP3L). Moreover, mitophagy is regulated in many metazoan cell types by parkin and PTEN-induced putative kinase protein 1 (PINK1), and mutations in the genes encoding these proteins have been linked to forms of Parkinson's disease. C1 [Youle, Richard J.; Narendra, Derek P.] NINDS, Biochem Sect, Surg Neurol Branch, NIH, Bethesda, MD 20892 USA. [Narendra, Derek P.] Med Res Council Mitochondrial Biol Unit, Cambridge CB2 2XY, England. RP Youle, RJ (reprint author), NINDS, Biochem Sect, Surg Neurol Branch, NIH, 35 Convent Dr,2C-917, Bethesda, MD 20892 USA. EM youler@ninds.nih.gov FU Intramural NIH HHS [Z99 NS999999] NR 72 TC 845 Z9 867 U1 51 U2 295 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1471-0072 J9 NAT REV MOL CELL BIO JI Nat. Rev. Mol. Cell Biol. PD JAN PY 2011 VL 12 IS 1 BP 9 EP 14 DI 10.1038/nrm3028 PG 6 WC Cell Biology SC Cell Biology GA 697UJ UT WOS:000285544000009 PM 21179058 ER PT J AU Skinner, M AF Skinner, Mhairi TI PROTEIN SYNTHESIS An expressive couple SO NATURE REVIEWS MOLECULAR CELL BIOLOGY LA English DT Editorial Material ID TRANSLATION C1 NCI, Nat Pathway Interact Database, Bethesda, MD 20892 USA. RP Skinner, M (reprint author), NCI, Nat Pathway Interact Database, Bethesda, MD 20892 USA. NR 2 TC 0 Z9 0 U1 1 U2 1 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1471-0072 J9 NAT REV MOL CELL BIO JI Nat. Rev. Mol. Cell Biol. PD JAN PY 2011 VL 12 IS 1 DI 10.1038/nrm3037 PG 1 WC Cell Biology SC Cell Biology GA 697UJ UT WOS:000285544000008 PM 21179057 ER PT J AU Kaler, SG AF Kaler, Stephen G. TI ATP7A-related copper transport diseases-emerging concepts and future trends SO NATURE REVIEWS NEUROLOGY LA English DT Review ID OCCIPITAL-HORN-SYNDROME; MARIE-TOOTH-DISEASE; P-TYPE ATPASE; HEREDITARY MOTOR NEUROPATHY; SPINAL MUSCULAR-ATROPHY; MOTTLED BRINDLED MOUSE; MENKES-DISEASE; ATP7A GENE; WILSON-DISEASE; CHOROID-PLEXUS AB This Review summarizes recent advances in understanding copper-transporting ATPase 1 (ATP7A), and examines the neurological phenotypes associated with dysfunction of this protein. Involvement of ATP7A in axonal outgrowth, synapse integrity and neuronal activation underscores the fundamental importance of copper metabolism to neurological function. Defects in ATP7A cause Menkes disease, an infantile-onset, lethal condition. Neonatal diagnosis and early treatment with copper injections enhance survival in patients with this disease, and can normalize clinical outcomes if mutant ATP7A molecules retain small amounts of residual activity. Gene replacement rescues a mouse model of Menkes disease, suggesting a potential therapeutic approach for patients with complete loss-of-function ATP7A mutations. Remarkably, a newly discovered ATP7A disorder-isolated distal motor neuropathy-has none of the characteristic clinical or biochemical abnormalities of Menkes disease or its milder allelic variant occipital horn syndrome (OHS), instead resembling Charcot-Marie-Tooth disease type 2. These findings indicate that ATP7A has a crucial but previously unappreciated role in motor neuron maintenance, and that the mechanism underlying ATP7A-related distal motor neuropathy is distinct from Menkes disease and OHS pathophysiology. Collectively, these insights refine our knowledge of the neurology of ATP7A-related copper transport diseases and pave the way for further progress in understanding ATP7A function. C1 Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Unit Human Copper Metab, Program Mol Med, NIH, Bethesda, MD 20892 USA. RP Kaler, SG (reprint author), Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Unit Human Copper Metab, Program Mol Med, NIH, Bldg 10 Room 10N313,10 Ctr Dr MSC 1853, Bethesda, MD 20892 USA. EM kalers@mail.nih.gov FU Eunice Kennedy Shriver National Institute of Child Health and Human Development (NIH) FX Written consent was obtained for publication of Figure 2a from the patient's mother. The author is supported by the Intramural Program of the Eunice Kennedy Shriver National Institute of Child Health and Human Development (NIH). The author apologizes to any colleagues whose work was not cited in this Review as a result of length constraints. NR 164 TC 156 Z9 157 U1 2 U2 27 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1759-4758 J9 NAT REV NEUROL JI Nat. Rev. Neurol. PD JAN PY 2011 VL 7 IS 1 BP 15 EP 29 DI 10.1038/nrneurol.2010.180 PG 15 WC Clinical Neurology SC Neurosciences & Neurology GA 705AG UT WOS:000286099300008 PM 21221114 ER PT J AU Blackstone, C O'Kane, CJ Reid, E AF Blackstone, Craig O'Kane, Cahir J. Reid, Evan TI Hereditary spastic paraplegias: membrane traffic and the motor pathway SO NATURE REVIEWS NEUROSCIENCE LA English DT Review ID AMYOTROPHIC-LATERAL-SCLEROSIS; REGULATES SYNAPTIC GROWTH; HEAVY-CHAIN KIF5A; ENDOPLASMIC-RETICULUM; AXONAL-TRANSPORT; ESCRT MACHINERY; PROTEIN SPASTIN; RECEPTOR TRAFFICKING; ALS2-DEFICIENT MICE; NUCLEOTIDE EXCHANGE AB Voluntary movement is a fundamental way in which animals respond to, and interact with, their environment. In mammals, the main CNS pathway controlling voluntary movement is the corticospinal tract, which encompasses connections between the cerebral motor cortex and the spinal cord. Hereditary spastic paraplegias (HSPs) are a group of genetic disorders that lead to a length-dependent, distal axonopathy of fibres of the corticospinal tract, causing lower limb spasticity and weakness. Recent work aimed at elucidating the molecular cell biology underlying the HSPs has revealed the importance of basic cellular processes-especially membrane trafficking and organelle morphogenesis and distribution-in axonal maintenance and degeneration. C1 [Reid, Evan] Univ Cambridge, Dept Med Genet, Cambridge Inst Med Res, Addenbrookes Hosp, Cambridge CB2 0XY, England. [O'Kane, Cahir J.] Univ Cambridge, Dept Genet, Cambridge CB2 3EH, England. [Blackstone, Craig] NINDS, Neurogenet Branch, NIH, Bethesda, MD 20892 USA. RP Reid, E (reprint author), Univ Cambridge, Dept Med Genet, Cambridge Inst Med Res, Addenbrookes Hosp, Wellcome Trust MRC Bldg, Cambridge CB2 0XY, England. EM ealr4@cam.ac.uk RI O'Kane, Cahir/C-4413-2011; Reid, Evan/F-3250-2010; OI Reid, Evan/0000-0003-1623-7304; O'Kane, Cahir/0000-0002-3488-2078 FU Wellcome Trust [082381, WT081386]; UK Medical Research Council; Tom Wahlig Stiftung; UK HSP Support Group; National Institute of Neurological Disorders and Stroke, US National Institutes of Health FX We are grateful to the members of our laboratories who have contributed to HSP-related work, and to the many HSP family members who have helped with our research. We thank T. Wahlig and H. Wahlig for their tireless work in promoting interactions among HSP researchers, clinicians and families. E. R. is a Wellcome Trust Senior Research Fellow in Clinical Science (grant 082381) and is also supported by the UK Medical Research Council, the Tom Wahlig Stiftung and the UK HSP Support Group. The work of C.J.O'K. on HSP is funded by Wellcome Trust (grant WT081386). C. B. is supported by the Intramural Research Program of the National Institute of Neurological Disorders and Stroke, US National Institutes of Health. NR 119 TC 128 Z9 130 U1 5 U2 25 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1471-0048 J9 NAT REV NEUROSCI JI Nat. Rev. Neurosci. PD JAN PY 2011 VL 12 IS 1 BP 31 EP 42 DI 10.1038/nrn2946 PG 12 WC Neurosciences SC Neurosciences & Neurology GA 696PN UT WOS:000285453900004 PM 21139634 ER PT J AU Morimoto, RI Driessen, AJM Hegde, RS Langer, T AF Morimoto, Richard I. Driessen, Arnold J. M. Hegde, Ramanujan S. Langer, Thomas TI The life of proteins: the good, the mostly good and the ugly SO NATURE STRUCTURAL & MOLECULAR BIOLOGY LA English DT Editorial Material C1 [Morimoto, Richard I.] Northwestern Univ, Dept Mol Biosci, Evanston, IL 60208 USA. [Morimoto, Richard I.] Rice Inst Biomed Res, Evanston, IL USA. [Driessen, Arnold J. M.] Univ Groningen, Dept Mol Microbiol, Groningen Biomol Sci, Groningen, Netherlands. [Driessen, Arnold J. M.] Univ Groningen, Zernike Inst Adv Mat, Inst Biotechnol, Groningen, Netherlands. [Hegde, Ramanujan S.] NICHHD, US Natl Inst Hlth, Bethesda, MD 20892 USA. [Langer, Thomas] Univ Cologne, Inst Genet, D-5000 Cologne, Germany. RP Morimoto, RI (reprint author), Northwestern Univ, Dept Mol Biosci, Evanston, IL 60208 USA. EM r-morimoto@northwestern.edu RI Driessen, Arnold/D-1876-2012; OI Driessen, Arnold J.M./0000-0001-9258-9104; Hegde, Ramanujan/0000-0001-8338-852X; Langer, Thomas/0000-0003-1250-1462 NR 0 TC 6 Z9 8 U1 0 U2 3 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1545-9985 J9 NAT STRUCT MOL BIOL JI Nat. Struct. Mol. Biol. PD JAN PY 2011 VL 18 IS 1 BP 1 EP 4 DI 10.1038/nsmb0111-1 PG 4 WC Biochemistry & Molecular Biology; Biophysics; Cell Biology SC Biochemistry & Molecular Biology; Biophysics; Cell Biology GA 703GQ UT WOS:000285966800001 PM 21209622 ER PT J AU Mears, JA Lackner, LL Fang, SM Ingerman, E Nunnari, J Hinshaw, JE AF Mears, Jason A. Lackner, Laura L. Fang, Shunming Ingerman, Elena Nunnari, Jodi Hinshaw, Jenny E. TI Conformational changes in Dnm1 support a contractile mechanism for mitochondrial fission SO NATURE STRUCTURAL & MOLECULAR BIOLOGY LA English DT Article ID CLATHRIN-MEDIATED ENDOCYTOSIS; DYNAMIN-RELATED GTPASE; IN-VIVO; MEMBRANE FISSION; STRUCTURAL BASIS; STALK REGION; PROTEIN; DOMAIN; CONSTRICTION; VISUALIZATION AB Mitochondria are dynamic organelles that undergo cycles of fission and fusion. The yeast dynamin-related protein Dnm1 has been localized to sites of mitochondrial division. Using cryo-EM, we have determined the three-dimensional (3D) structure of Dnm1 in a GTP-bound state. The 3D map showed that Dnm1 adopted a unique helical assembly when compared with dynamin, which is involved in vesicle scission during endocytosis. Upon GTP hydrolysis, Dnm1 constricted liposomes and subsequently dissociated from the lipid bilayer. The magnitude of Dnm1 constriction was substantially larger than the decrease in diameter previously reported for dynamin. We postulate that the larger conformational change is mediated by a flexible Dnm1 structure that has limited interaction with the underlying bilayer. Our structural studies support the idea that Dnm1 has a mechanochemical role during mitochondrial division. C1 [Mears, Jason A.; Fang, Shunming; Hinshaw, Jenny E.] NIDDKD, Lab Cell Biochem & Biol, NIH, Bethesda, MD 20892 USA. [Lackner, Laura L.; Ingerman, Elena; Nunnari, Jodi] Univ Calif Davis, Ctr Genet & Dev, Dept Mol & Cellular Biol, Davis, CA 95616 USA. RP Hinshaw, JE (reprint author), NIDDKD, Lab Cell Biochem & Biol, NIH, Bethesda, MD 20892 USA. EM jennyh@helix.nih.gov FU US National Institutes of Health (NIH), National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK); NIH [R01GM062942, 1F32GM078749] FX We thank D. Winkler and A. Steven for technical assistance in acquiring tomograms and P. Flicker, J. Hanover, W. Prinz, J. Evans and J. Heymann for critical discussions and reading of the manuscript. This work was supported by the Intramural Research Program of the US National Institutes of Health (NIH), National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) (J.E.H.) and the Nancy Nossal Fellowship of the NIH, NIDDK (J.A.M.). J.N. is supported by NIH grant R01GM062942, and L.L.L. is supported by NIH postdoctoral fellowship 1F32GM078749. NR 56 TC 130 Z9 134 U1 2 U2 14 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1545-9985 J9 NAT STRUCT MOL BIOL JI Nat. Struct. Mol. Biol. PD JAN PY 2011 VL 18 IS 1 BP 20 EP + DI 10.1038/nsmb.1949 PG 8 WC Biochemistry & Molecular Biology; Biophysics; Cell Biology SC Biochemistry & Molecular Biology; Biophysics; Cell Biology GA 703GQ UT WOS:000285966800004 PM 21170049 ER PT J AU Bugreev, DV Pezza, RJ Mazina, OM Voloshin, ON Camerini-Otero, RD Mazin, AV AF Bugreev, Dmitry V. Pezza, Roberto J. Mazina, Olga M. Voloshin, Oleg N. Camerini-Otero, R. Daniel Mazin, Alexander V. TI The resistance of DMC1 D-loops to dissociation may account for the DMC1 requirement in meiosis SO NATURE STRUCTURAL & MOLECULAR BIOLOGY LA English DT Article ID DOUBLE-STRAND-BREAK; SYNAPTONEMAL COMPLEX-FORMATION; PROMOTES BRANCH MIGRATION; BLOOMS-SYNDROME HELICASE; MEIOTIC RECOMBINATION; HOMOLOGOUS RECOMBINATION; HOLLIDAY JUNCTIONS; SACCHAROMYCES-CEREVISIAE; CHROMOSOME SYNAPSIS; RAD51 RECOMBINASE AB The ubiquitously expressed Rad51 recombinase and the meiosis-specific Dmc1 recombinase promote the formation of strand-invasion products (D-loops) between homologous molecules. Strand-invasion products are processed by either the double-strand break repair (DSBR) or synthesis-dependent strand annealing (SDSA) pathway. D-loops destined to be processed by SDSA need to dissociate, producing non-crossovers, and those destined for DSBR should resist dissociation to generate crossovers. The mechanism that channels recombination intermediates into different homologous-recombination pathways is unknown. Here we show that D-loops in a human DMC1-driven reaction are substantially more resistant to dissociation by branch-migration proteins such as RAD54 than those formed by RAD51. We propose that the intrinsic resistance to dissociation of DMC1 strand-invasion intermediates may account for why DMC1 is essential to ensure the proper segregation of chromosomes in meiosis. C1 [Pezza, Roberto J.; Voloshin, Oleg N.; Camerini-Otero, R. Daniel] NIDDKD, Genet & Biochem Branch, US Natl Inst Hlth, Bethesda, MD 20892 USA. [Bugreev, Dmitry V.; Mazina, Olga M.; Mazin, Alexander V.] Drexel Univ, Coll Med, Dept Biochem & Mol Biol, Philadelphia, PA 19104 USA. [Mazin, Alexander V.] Russian Acad Sci, Inst Cytol & Genet, Siberian Branch, Novosibirsk 630090, Russia. RP Camerini-Otero, RD (reprint author), NIDDKD, Genet & Biochem Branch, US Natl Inst Hlth, Bethesda, MD 20892 USA. EM rdcamerini@mail.nih.gov; amazin@drexelmed.edu FU US National Institutes of Health [CA100839, MH084119]; Leukemia and Lymphoma Society Scholar Award [1054-09]; US National Institute of Diabetes and Digestive and Kidney Diseases FX We thank P. Sung (Yale University) and W. Holloman (Cornell University) for RAD51 and BLM expression vectors, members of the Camerini-Otero and Mazin labs for comments and discussion, and M. Lichten and P. Hsieh for critical reading of this manuscript. This work was supported by US National Institutes of Health grants CA100839 and MH084119, the Leukemia and Lymphoma Society Scholar Award 1054-09 (to A.V.M.) and the Intramural Research Program of the US National Institute of Diabetes and Digestive and Kidney Diseases (to R.D.C.-O.). NR 60 TC 24 Z9 24 U1 1 U2 7 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1545-9985 J9 NAT STRUCT MOL BIOL JI Nat. Struct. Mol. Biol. PD JAN PY 2011 VL 18 IS 1 BP 56 EP + DI 10.1038/nsmb.1946 PG 6 WC Biochemistry & Molecular Biology; Biophysics; Cell Biology SC Biochemistry & Molecular Biology; Biophysics; Cell Biology GA 703GQ UT WOS:000285966800009 PM 21151113 ER PT J AU Jia, L Yi, XF Zhang, ZB Zhuang, ZP Li, J Chambers, SK Kong, BH Zheng, W AF Jia, L. Yi, X. F. Zhang, Z. B. Zhuang, Z. P. Li, J. Chambers, S. K. Kong, B. H. Zheng, W. TI Prohibitin as a novel target protein of luteinizing hormone in ovarian epithelial carcinogenesis SO NEOPLASMA LA English DT Article DE Gonadotropin; Luteinizing hormone; Prohibitin; Ovarian cancer ID CANCER CELLS; EXPRESSION; PROLIFERATION; RISK; FIBROBLASTS; APOPTOSIS; SUBTYPES; NUCLEUS; REGION; TUMORS AB The exact role of follicle-stimulating hormone (FSH) and luteinizing hormone (LH) in ovarian epithelial carcinoma (OEC) development has not been yet characterized. This prompted us to identify particular proteins to better understand the underlying mechanism. Total proteins from ovarian epithelial tumor (OET) cells treated with gonadotropins were analyzed by proteomics. Western blot and immunohistochemistry were used to validate the target protein (prohibitin) and to detect its expression in human ovarian tissue of serous tumors. As the results, prohibitin was found to be significantly up-regulated by LH, with a maximum of 2.5-fold increase at the concentration of 200 mIU/mL. The expression of prohibitin was steadily decreased from benign serous cystadenomas to borderline tumors and serous carcinomas (P < 0.0001). The difference between any two groups was significant (P < 0.001). Collectively, data from this study indicate that prohibitin is one LH-associated protein and it may be protective of ovarian cancer development and progression, supporting that LH may play an inhibitory role in ovarian tumorigenesis. C1 [Jia, L.; Kong, B. H.; Zheng, W.] Shandong Univ, Qilu Hosp, Dept Obstet & Gynecol, Jinan 250012, Peoples R China. [Yi, X. F.] Fudan Univ, Hosp Obstet & Gynecol, Shanghai 200433, Peoples R China. [Zhang, Z. B.] Jiao Tong Univ, Shanghai Municipal Hosp 1, Dept Obstet & Gynecol, Shanghai, Peoples R China. [Zhuang, Z. P.; Li, J.] Natl Inst Neurol Disorders & Stroke, Mol Pathogenesis Unit, Surg Neurol Branch, NIH, Bethesda, MD 20892 USA. [Jia, L.; Chambers, S. K.; Zheng, W.] Univ Arizona, Arizona Canc Ctr, Tucson, AZ USA. [Zheng, W.] Univ Arizona, Coll Med, Dept Pathol, Tucson, AZ 85721 USA. [Zheng, W.] Univ Arizona, Coll Med, Dept Obstet & Gynecol, Tucson, AZ 85721 USA. RP Jia, L (reprint author), Shandong Univ, Qilu Hosp, Dept Obstet & Gynecol, Jinan 250012, Peoples R China. EM kongbeihua@sdu.edu.cn; zhengw@email.arizona.edu FU National Natural Science Foundation of China [30901590]; Arizona Cancer Center [P30 CA23074]; University of Arizona Department of Pathology FX Dr. Lin Jia was a co-trained PhD candidate of Shandong University, China. The work was supported partly by the National Natural Science Foundation of China (No. 30901590) to LJ, Arizona Cancer Center Core Grant (P30 CA23074), Arizona Cancer Center Better Than Ever Grant, and University of Arizona Department of Pathology start up fund to WZ. We thank Dr. Jun Wang at Tufts University (Boston, Massachusetts) for her excellent statistical data analysis for this project. NR 30 TC 9 Z9 11 U1 0 U2 3 PU VEDA, SLOVAK ACAD SCIENCES PI BRASTISLAVA PA DUBRAVSKA CESTA 9, 842 34 BRASTISLAVA, SLOVAKIA SN 0028-2685 J9 NEOPLASMA JI Neoplasma PY 2011 VL 58 IS 2 BP 104 EP 109 DI 10.4149/neo_2011_02_104 PG 6 WC Oncology SC Oncology GA 765HI UT WOS:000290695700002 PM 21275458 ER PT J AU O'Seaghdha, CM Fox, CS AF O'Seaghdha, Conall M. Fox, Caroline S. TI Genetics of Chronic Kidney Disease SO NEPHRON CLINICAL PRACTICE LA English DT Article DE Chronic kidney disease; Genetic variation; Genome-wide association studies; Diabetic nephropathy; End-stage renal disease ID STAGE RENAL-DISEASE; MANGANESE SUPEROXIDE-DISMUTASE; TYPE-2 DIABETIC-PATIENTS; GENOME-WIDE ASSOCIATION; INCIDENT DIALYSIS PATIENTS; URINARY ALBUMIN EXCRETION; AFRICAN-AMERICANS; FECHTNER-SYNDROME; IGA NEPHROPATHY; FAMILIAL PREDISPOSITION AB The current review collates what is already known of the genetics of chronic kidney disease (CKD), and focuses on new trends in genome-wide assessment of the inherited component of susceptibility to this condition. Early efforts to identify kidney disease susceptibility genetic loci using linkage and candidate gene strategies proved disappointing. More recently, genome-wide association studies have yielded highly promising results suggesting a number of potential candidate genes and genomic regions that may contribute to the pathogenesis of CKD. Renal failure susceptibility genes identified by these methods, such as MYH9, have yielded novel insights into the pathogenesis of CKD. Genome-wide association studies of CKD are beginning to define the genomic architecture of kidney disease and will impact our understanding of how genetic variation influences susceptibility to this condition. Copyright (C) 2010 S. Karger AG, Basel C1 [O'Seaghdha, Conall M.; Fox, Caroline S.] NHLBI, Framingham Heart Study, Framingham, MA 01702 USA. [O'Seaghdha, Conall M.] Massachusetts Gen Hosp, Brigham & Womens Hosp, Div Renal, Boston, MA 02114 USA. [O'Seaghdha, Conall M.; Fox, Caroline S.] Harvard Univ, Sch Med, Boston, MA USA. [Fox, Caroline S.] Brigham & Womens Hosp, Div Endocrinol, Boston, MA 02115 USA. RP Fox, CS (reprint author), NHLBI, Framingham Heart Study, 73 Mt Wayte Ave,Suite 2, Framingham, MA 01702 USA. EM foxca@nhlbi.nih.gov NR 88 TC 8 Z9 8 U1 0 U2 4 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 1660-2110 J9 NEPHRON CLIN PRACT JI Nephron. Clin. Pract. PY 2011 VL 118 IS 1 BP C55 EP C63 DI 10.1159/000320905 PG 9 WC Urology & Nephrology SC Urology & Nephrology GA 679JD UT WOS:000284156800009 PM 21071974 ER PT J AU Basselin, M Ramadan, E Chen, M Rapoport, SI AF Basselin, Mireille Ramadan, Epolia Chen, Mei Rapoport, Stanley I. TI Anti-Inflammatory Effects of Chronic Aspirin on Brain Arachidonic Acid Metabolites (Retracted article. See vol. 40, pg. 1094, 2015) SO NEUROCHEMICAL RESEARCH LA English DT Article; Retracted Publication DE Aspirin; Neuroinflammation; Eicosanoids; Arachidonic acid; Lipoxin A(4); 15-epi-lipoxin A(4) ID LOW-DOSE ASPIRIN; FACTOR-KAPPA-B; LIPOXIN A(4); RAT-BRAIN; TRIGGERED 15-EPI-LIPOXINS; CYCLOOXYGENASE ISOZYMES; ALZHEIMERS-DISEASE; GENE-EXPRESSION; LEUKOTRIENE B-4; EICOSANOIDS AB Pro-inflammatory and anti-inflammatory mediators derived from arachidonic acid (AA) modulate peripheral inflammation and its resolution. Aspirin (ASA) is a unique non-steroidal anti-inflammatory drug, which switches AA metabolism from prostaglandin E-2 (PGE(2)) and thromboxane B-2 (TXB2) to lipoxin A(4) (LXA(4)) and 15-epi-LXA(4). However, it is unknown whether chronic therapeutic doses of ASA are anti-inflammatory in the brain. We hypothesized that ASA would dampen increases in brain concentrations of AA metabolites in a rat model of neuroinflammation, produced by a 6-day intracerebroventricular infusion of bacterial lipopolysaccharide (LPS). In rats infused with LPS (0.5 ng/h) and given ASA-free water to drink, concentrations in high-energy microwaved brain of PGE(2), TXB2 and leukotriene B-4 (LTB4) were elevated. In rats infused with artificial cerebrospinal fluid, 6 weeks of treatment with a low (10 mg/kg/day) or high (100 mg/kg/day) ASA dose in drinking water decreased brain PGE(2), but increased LTB4, LXA(4) and 15-epi-LXA(4) concentrations. Both doses attenuated the LPS effects on PGE(2), and TXB2. The increments in LXA(4) and 15-epi-LXA(4) caused by high-dose ASA were significantly greater in LPS-infused rats. The ability of ASA to increase anti-inflammatory LXA(4) and 15-epi-LXA(4) and reduce pro-inflammatory PGE(2) and TXB2 suggests considering aspirin further for treating clinical neuroinflammation. C1 [Basselin, Mireille; Ramadan, Epolia; Chen, Mei; Rapoport, Stanley I.] NIA, Brain Physiol & Metab Sect, NIH, Bethesda, MD 20892 USA. RP Ramadan, E (reprint author), NIA, Brain Physiol & Metab Sect, NIH, Bldg 9,Room 1S126,9000 Rockville Pike, Bethesda, MD 20892 USA. EM ramadanir@mail.nih.gov FU National Institute on Aging, NIH FX This work was supported entirely by the Intramural Research Program of the National Institute on Aging, NIH. None of the authors has a financial or other conflict of interest related to this work. NR 63 TC 17 Z9 18 U1 1 U2 8 PU SPRINGER/PLENUM PUBLISHERS PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0364-3190 EI 1573-6903 J9 NEUROCHEM RES JI Neurochem. Res. PD JAN PY 2011 VL 36 IS 1 BP 139 EP 145 DI 10.1007/s11064-010-0282-4 PG 7 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA 711KA UT WOS:000286589000017 PM 20981485 ER PT J AU Kaminski, RM Nunez-Taltavull, JF Budziszewska, B Lason, W Gasior, M Zapata, A Shippenberg, TS Witkin, JM AF Kaminski, Rafal M. Nunez-Taltavull, Juan F. Budziszewska, Boguslawa Lason, Wladyslaw Gasior, Maciej Zapata, Agustin Shippenberg, Toni S. Witkin, Jeffrey M. TI Effects of Cocaine-Kindling on the Expression of NMDA Receptors and Glutamate Levels in Mouse Brain SO NEUROCHEMICAL RESEARCH LA English DT Article DE Cocaine; Seizure; Kindling; Glutamate; Microdialysis; NMDA receptor ID METHYL-D-ASPARTATE; EXCITATORY AMINO-ACIDS; IN-VIVO MICRODIALYSIS; EXTRACELLULAR GLUTAMATE; INDUCED CONVULSIONS; REVERSE TOLERANCE; RAT; HIPPOCAMPUS; ANTAGONISTS; MICE AB In the present study we examined the effects of cocaine seizure kindling on the expression of NMDA receptors and levels of extracellular glutamate in mouse brain. Quantitative autoradiography did not reveal any changes in binding of [(3)H] MK-801 to NMDA receptors in several brain regions. Likewise, in situ hybridization and Western blotting revealed no alteration in expression of the NMDA receptor subunits, NR1 and NR2B. Basal overflow of glutamate in the ventral hippocampus determined by microdialysis in freely moving animals also did not differ between cocaine-kindled and control groups. Perfusion with the selective excitatory amino acid transporter inhibitor, pyrrolidine-2,4-dicarboxylic acid (tPDC, 0.6 mM), increased glutamate overflow confirming transport inhibition. Importantly, KCl-evoked glutamate overflow under tPDC perfusion was significantly higher in cocaine-kindled mice than in control mice. These data suggest that enhancement of depolarization stimulated glutamate release may be one of the mechanisms underlying the development of increased seizure susceptibility after cocaine kindling. C1 [Kaminski, Rafal M.] UCB Pharma SA, CNS Res, Epilepsy Pharmacol, B-1420 Braine I Alleud, Belgium. [Kaminski, Rafal M.; Gasior, Maciej; Witkin, Jeffrey M.] Natl Inst Drug Abuse, Drug Dev Grp, Behav Neurosci Branch, NIH, Baltimore, MD 21224 USA. [Kaminski, Rafal M.; Nunez-Taltavull, Juan F.; Zapata, Agustin; Shippenberg, Toni S.] Natl Inst Drug Abuse, Integrat Neurosci Sect, Behav Neurosci Branch, NIH, Baltimore, MD 21224 USA. [Budziszewska, Boguslawa; Lason, Wladyslaw] Polish Acad Sci, Inst Pharmacol, Dept Expt Neuroendocrinol, Krakow, Poland. RP Kaminski, RM (reprint author), UCB Pharma SA, CNS Res, Epilepsy Pharmacol, Chemin Foriest,R9, B-1420 Braine I Alleud, Belgium. EM rafal.kaminski@ucb.com FU NIDA, NIH FX This research was supported by NIDA Intramural Research Program of NIH. NR 37 TC 8 Z9 8 U1 1 U2 5 PU SPRINGER/PLENUM PUBLISHERS PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0364-3190 J9 NEUROCHEM RES JI Neurochem. Res. PD JAN PY 2011 VL 36 IS 1 BP 146 EP 152 DI 10.1007/s11064-010-0284-2 PG 7 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA 711KA UT WOS:000286589000018 PM 20927585 ER PT J AU Holl, AK Ille, R Wilkinson, L Otti, DV Hodl, E Herranhof, B Reisinger, KM Muller, N Painold, A Holl, EM Letmaier, M Bonelli, RM AF Holl, Anna K. Ille, Rottraut Wilkinson, Leonora Otti, Daniela V. Hoedl, Elfriede Herranhof, Brigitte Reisinger, Karin M. Mueller, Nicole Painold, Annamaria Holl, Etienne M. Letmaier, Martin Bonelli, Raphael M. TI Impaired Ideomotor Limb Apraxia in Cortical and Subcortical Dementia: A Comparison of Alzheimer's and Huntington's Disease SO NEURODEGENERATIVE DISEASES LA English DT Article DE Huntington's disease; Alzheimer's disease; Apraxia; Neuropsychological assessment ID PROGRESSIVE SUPRANUCLEAR PALSY; PARKINSONS-DISEASE; IMITATING GESTURES; BASAL GANGLIA; MOTOR; CORTEX; PATHOPHYSIOLOGY; MOVEMENTS; PRAXIS; SCALE AB Background: Although ideomotor limb apraxia is often considered to occur only in dementia with cortical involvement like Alzheimer's disease (AD), it is also frequently seen in dementia with subcortical degeneration like Huntington's disease (HD). Methods: To assess the occurrence of ideomotor limb apraxia, 46 patients with HD (27 men) and 37 patients with AD (16 men), matched for cognitive performance, were assessed with an apraxia test battery containing tests of the imitation of meaningless hand and finger gestures, the performance of meaningful gestures and of pantomimic movements. Results: There was a high frequency of ideomotor limb apraxia in both AD and HD patients. For the assessment of hands' imitation 13.5% of the AD patients and 41.3% of the HD patients were apraxic, for fingers' imitation 21.6% (AD) and 41.3% (HD) were apraxic, for gestures 27.0% (AD) and 32.6% (HD), and for the assessment of pantomimic movements 24.3% (AD) and 52.2% (HD) showed apraxia. In the AD patients, disease severity was related to the occurrence of apraxia. Conclusions: Ideomotor limb apraxia is a common sign in both groups of patients, occurring in a high percentage. For particular neuropsychological deficits, including ideomotor limb apraxia, a division of dementia in a subcortical and cortical subtype seems to be clinically not meaningful. Copyright (C) 2011 S. Karger AG, Basel C1 [Holl, Anna K.; Otti, Daniela V.; Herranhof, Brigitte; Reisinger, Karin M.; Mueller, Nicole; Painold, Annamaria; Letmaier, Martin] Graz Med Univ, Univ Clin Psychiat, Dept Psychiat, AT-8036 Graz, Austria. [Holl, Etienne M.] Graz Med Univ, Dept Neurosurg, AT-8036 Graz, Austria. [Ille, Rottraut] Karl Franzens Univ Graz, Inst Psychol, Graz, Austria. [Hoedl, Elfriede] Krankenhaus Barmherzigen Bruder Graz Eggenberg, Dept Neurol & Psychiat, Graz, Austria. [Bonelli, Raphael M.] Paracelsus Med Univ, Dept Neurol, Salzburg, Austria. [Wilkinson, Leonora] Natl Inst Neurol Disorders & Stroke, Brain Stimulat Unit, Bethesda, MD USA. RP Holl, AK (reprint author), Graz Med Univ, Univ Clin Psychiat, Dept Psychiat, Auenbruggerpl 31, AT-8036 Graz, Austria. EM anna.holl@klinikum-graz.at FU Parkinson's UK [F-0608] NR 45 TC 5 Z9 6 U1 1 U2 4 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 1660-2854 J9 NEURODEGENER DIS JI Neurodegener. Dis. PY 2011 VL 8 IS 4 BP 208 EP 215 DI 10.1159/000322230 PG 8 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 763LT UT WOS:000290559000007 PM 21212634 ER PT J AU Gao, JJ Xu, H Weinberg, C Huang, XM Park, Y Hollenbeck, A Blair, A Schatzkin, A Burch, L Chen, HL AF Gao, Jianjun Xu, Hong Weinberg, Clarice Huang, Xuemei Park, Yikyung Hollenbeck, Albert Blair, Aaron Schatzkin, Arthur Burch, Lauranell Chen, Honglei TI An Exploratory Study on the CHRNA3-CHRNA5-CHRNB4 Cluster, Smoking, and Parkinson's Disease SO NEURODEGENERATIVE DISEASES LA English DT Article DE Parkinson's disease; Smoking; CHRNA3-CHRNA5-CHRNB4 cluster; Nicotine dependence ID LUNG-CANCER; SUSCEPTIBILITY LOCUS; NICOTINIC RECEPTORS; TARGETS; RISK AB Background: Smokers have a lower risk of Parkinson's disease (PD). Recent genome-wide association studies (GWAS) have consistently linked several single nucleotide polymorphisms (SNPs) in the CHRNA3-CHRNA5-CHRNB4 cluster on chromosome 15.q25 to smoking behaviors and nicotine dependence. Investigations into these SNPs may help explain the nature and mechanisms of the smoking-PD relationship. Objective: To examine whether the genetic variations that were consistently associated with smoking or nicotine dependence in recent GWAS also predict the risk of PD. Methods: This is a population-based case-control study of 788 physician-diagnosed PD patients and 911 controls, all non-Hispanic Whites. Seven SNPs were selected based on findings from recent GWAS on smoking and nicotine dependence, all from the nicotinic acetylcholine receptor subunits (CHRN) A3-A5-B4. Odds ratios (ORs) and 95% confidence intervals were derived from logistic regression models under the assumption of logit-additive allelic effects. Results: Four SNPs in linkage disequilibrium from the CHRNA3-CHRNA5-CHRNB4 cluster were associated with smoking duration (OR >1.3, p < 0.05). However, none of the SNPs from this cluster was associated with PD risk in the overall analysis or after stratifying on smoking status. Conclusion: This preliminary analysis does not support a relationship between these smoking-related GWAS SNPs and PD. Copyright (C) 2011 S. Karger AG, Basel C1 [Gao, Jianjun; Chen, Honglei] NIEHS, Epidemiol Branch, Res Triangle Pk, NC 27709 USA. [Xu, Hong; Burch, Lauranell] NIEHS, Mol Genet Core Facil, Res Triangle Pk, NC 27709 USA. [Weinberg, Clarice] NIEHS, Biostat Branch, Res Triangle Pk, NC 27709 USA. [Huang, Xuemei] Penn State Univ, Milton S Hershey Med Ctr, Dept Neurol, Hershey, PA 17033 USA. [Park, Yikyung; Schatzkin, Arthur] NCI, Nutr Epidemiol Branch, Rockville, MD USA. [Blair, Aaron] NCI, Occupat & Environm Epidemiol Branch, Rockville, MD USA. [Hollenbeck, Albert] AARP, Washington, DC USA. RP Chen, HL (reprint author), NIEHS, Epidemiol Branch, 111 TW Alexander Dr,POB 12233,Mail Drop A3-05, Res Triangle Pk, NC 27709 USA. EM chenh2@niehs.nih.gov OI Xu, Hong/0000-0003-1995-4675; Chen, Honglei/0000-0003-3446-7779; Park, Yikyung/0000-0002-6281-489X FU NIH [R01 NS060722]; National Institute of Environmental Health Sciences [Z01-ES-101986]; National Cancer Institute [Z01 CP010196-02] FX The authors are grateful to the continuous contribution of the NIH-AARP Diet and Health Study participants. We also thank Drs. Dana Hancock and Min Shi for their comments on the manuscript. This study was supported by the intramural research program of the NIH, the National Institute of Environmental Health Sciences (Z01-ES-101986), the National Cancer Institute (Z01 CP010196-02), and an NIH extramural grant (R01 NS060722) to Dr. Huang. NR 11 TC 3 Z9 3 U1 0 U2 3 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 1660-2854 J9 NEURODEGENER DIS JI Neurodegener. Dis. PY 2011 VL 8 IS 5 BP 296 EP 299 DI 10.1159/000323190 PG 4 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 776MH UT WOS:000291538700004 PM 21228559 ER PT J AU Li, XR Kumar, A Lee, C Tang, ZS Li, Y Arjunan, P Hou, X Zhang, F AF Li, Xuri Kumar, Anil Lee, Chunsik Tang, Zhongshu Li, Yang Arjunan, Pachiappan Hou, Xu Zhang, Fan BE Chang, RCC TI Can VEGF-B Be Used to Treat Neurodegenerative Diseases? SO NEURODEGENERATIVE DISEASES - PROCESSES, PREVENTION, PROTECTION AND MONITORING LA English DT Article; Book Chapter ID ENDOTHELIAL GROWTH-FACTOR; MODERATE ALZHEIMERS-DISEASE; PARKINSONS-DISEASE; HUNTINGTONS-DISEASE; IN-VIVO; MACULAR DEGENERATION; TRANSGENIC MICE; DOPAMINERGIC-NEURONS; DIABETIC-RETINOPATHY; FAMILY-MEMBERS C1 [Li, Xuri; Kumar, Anil; Lee, Chunsik; Tang, Zhongshu; Li, Yang; Arjunan, Pachiappan; Hou, Xu; Zhang, Fan] NEI, NIH, Rockville, MD 20892 USA. RP Li, XR (reprint author), NEI, NIH, Rockville, MD 20892 USA. NR 117 TC 0 Z9 0 U1 0 U2 0 PU INTECH EUROPE PI RIJEKA PA JANEZA TRDINE9, RIJEKA, 51000, CROATIA BN 978-953-307-485-6 PY 2011 BP 387 EP 406 D2 10.5772/1252 PG 20 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA BG1KI UT WOS:000386854400017 ER PT J AU Stranahan, AM Arumugam, TV Mattson, MP AF Stranahan, Alexis M. Arumugam, Thiruma V. Mattson, Mark P. TI Lowering Corticosterone Levels Reinstates Hippocampal Brain-Derived Neurotropic Factor and Trkb Expression without Influencing Deficits in Hypothalamic Brain-Derived Neurotropic Factor Expression in Leptin Receptor-Deficient Mice SO NEUROENDOCRINOLOGY LA English DT Article DE Diabetes; Glucocorticoid; Neurotropic factor; Hippocampus; Hypothalamus ID SYNAPTIC PLASTICITY; DIABETIC MICE; OBESITY; BDNF; METABOLISM; NEURONS; MOUSE AB Background/Aims: Changes in the glucocorticoid milieu contribute to alterations in neurotropic factor expression across multiple brain regions. Insulin-resistant diabetes is often accompanied by dysregulation of adrenal steroid production in humans and animal models. Leptin receptor-deficient mice (db/db) show reduced expression of brain-derived neurotropic factor (BDNF) in the hippocampus and increases in circulating corticosterone levels, but the extent to which elevated corticosterone levels mediate deficits in BDNF expression has not been determined. Methods: Using in situ hybridization, we measured the expression of BDNF, its receptor TrkB, and neurotropin-3 (NT-3) in the hippocampus and hypothalamus of db/db mice and wild-type controls following adrenalectomy and low-dose corticosterone replacement (ADX+CORT) or sham operation. Results: Lowering corticosterone levels restored BDNF and TrkB expression in the hippocampus of db/db mice. However, deficits in hypothalamic BDNF expression were not reversed following ADX+CORT. There was no effect of genotype or adrenalectomy on NT-3 expression in any brain region examined. Conclusion: Leptin receptor-deficient mice exhibit reduced BDNF expression in the hippocampus and hypothalamus. In the db/db mouse hippocampus, suppression of BDNF occurs in a glucocorticoid-dependent fashion, while hypothalamic BDNF expression is reduced via glucocorticoid-independent mechanisms. Region-specific signals therefore play a role in the interaction between corticosteroids and neurotropic factor expression. Copyright (C) 2010 S. Karger AG, Basel C1 [Stranahan, Alexis M.] Johns Hopkins Univ, Dept Psychol & Brain Sci, Baltimore, MD 21218 USA. [Stranahan, Alexis M.; Arumugam, Thiruma V.; Mattson, Mark P.] NIA, Cellular & Mol Neurosci Sect, Lab Neurosci, Baltimore, MD 21224 USA. RP Stranahan, AM (reprint author), Johns Hopkins Univ, Dept Psychol & Brain Sci, 3400 N Charles St, Baltimore, MD 21218 USA. EM astrana1@jhu.edu RI Arumugam, Thiruma/B-4898-2011; Mattson, Mark/F-6038-2012 FU Ford Foundation; National Institute on Aging FX This work was supported by a Ford Foundation Fellowship to A.M.S., and by the National Institute on Aging Intramural Research Program. We are grateful to Rebecca Haberman for insightful suggestions and Michela Gallagher for use of resources for the in situ hybridization experiments. NR 21 TC 17 Z9 17 U1 1 U2 6 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 0028-3835 J9 NEUROENDOCRINOLOGY JI Neuroendocrinology PY 2011 VL 93 IS 1 BP 58 EP 64 DI 10.1159/000322808 PG 7 WC Endocrinology & Metabolism; Neurosciences SC Endocrinology & Metabolism; Neurosciences & Neurology GA 721IX UT WOS:000287347900007 PM 21160171 ER PT J AU Schraml, FV Goslar, PW Baxter, L Beason-Held, LL AF Schraml, Frank V. Goslar, Pamela W. Baxter, Leslie Beason-Held, Lori L. TI Thyroid stimulating hormone and cognition during severe, transient hypothyroidism SO NEUROENDOCRINOLOGY LETTERS LA English DT Article DE thyroid stimulating hormone; cognition; hypothyroidism; depression; working memory ID CEREBRAL-BLOOD-FLOW; RAT-BRAIN; MOOD DISORDERS; TRIIODOTHYRONINE; DEPRESSION; MEMORY AB OBJECTIVE: The purpose of our pilot study was to explore the relationship between serum thyroid stimulating hormone (TSH) levels during overt hypothyroidism (OH) and hypothyroid-related neuropsychological symptoms. We hypothesized that TSH level may reflect the degree of 'brain hypothyroidism' such that an inverse correlation may exist between serum TSH and cognitive function in patients experiencing overt hypothyroidism (OH), and sought to explore this hypothesis. METHODS: Eleven thyroidectomized patients underwent neuropsychological and thyroid function testing while overtly hypothyroid, and again following thyroid hormone replacement. Their test performance was compared with that of eleven healthy controls at a similarly separated two points in time, and the change over time for the patient group and the controls was likewise assessed and compared. The patients' neuropsychological test scores were then correlated with their serum TSH levels while hypothyroid. RESULTS: The patients' performance while hypothyroid was worse than that of the controls in only one neurocognitive measure - Working Memory Index. The subjects improved similarly or to a greater degree than the controls, when the subjects were thyroid hormone replaced, on all but one neurocognitive measure - Thurstone Word Fluency. TSH level during hypothyroidism was inversely proportional to the patients' performance on these same two measures, but no others. CONCLUSION: Serum TSH level during hypothyroidism was inversely proportional to performance on the only two neurocognitive measures evidencing an adverse effect from hypothyroidism in our cohort. This suggests thatserum TSH level may reflect the severity of 'brain hypothyroidism' during the overt stage of this condition. C1 [Schraml, Frank V.] St Josephs Hosp, Barrow Neurol Inst, Dept Radiol, Phoenix, AZ 85013 USA. [Schraml, Frank V.] St Josephs Hosp, Barrow Neurol Inst, Dept Psychiat, Phoenix, AZ 85013 USA. [Beason-Held, Lori L.] NIA, Lab Personal & Cognit, NIH, Baltimore, MD 21224 USA. RP Schraml, FV (reprint author), St Josephs Hosp, Barrow Neurol Inst, Dept Radiol, 350 W Thomas Rd, Phoenix, AZ 85013 USA. EM fvschraml@yahoo.com FU NIH, National Institute on Aging FX Dr. Beason-Held's work was supported by the Intramural Research Program of the NIH, National Institute on Aging. The opinions expressed in this work are those of the authors, and do not reflect the official policy or the position of the U.S. Department of the Navy, U.S. Department of Defense, or the U.S. government. NR 31 TC 7 Z9 7 U1 0 U2 2 PU MAGHIRA & MAAS PUBLICATIONS PI STOCKHOLM PA PO BOX 26132, S-100 41 STOCKHOLM, SWEDEN SN 0172-780X J9 NEUROENDOCRINOL LETT JI Neuroendocrinol. Lett. PY 2011 VL 32 IS 3 BP 279 EP 285 PG 7 WC Endocrinology & Metabolism; Neurosciences SC Endocrinology & Metabolism; Neurosciences & Neurology GA 809XJ UT WOS:000294089700011 PM 21712772 ER PT J AU Jefferson, AL Massaro, JM Beiser, AS Seshadri, S Larson, MG Wolf, PA Au, R Benjamin, EJ AF Jefferson, Angela L. Massaro, Joseph M. Beiser, Alexa S. Seshadri, Sudha Larson, Martin G. Wolf, Philip A. Au, Rhoda Benjamin, Emelia J. TI Inflammatory Markers and Neuropsychological Functioning: The Framingham Heart Study SO NEUROEPIDEMIOLOGY LA English DT Article DE Memory; Executive functioning; Inflammation; Cognition; WRAT-3 reading ID C-REACTIVE PROTEIN; STROKE RISK PROFILE; ALZHEIMERS-DISEASE; COGNITIVE DECLINE; AFRICAN-AMERICAN; TEST-PERFORMANCE; CARDIOVASCULAR-DISEASE; READING LEVEL; WHITE ELDERS; BRAIN VOLUME AB Background/Aims: We hypothesized that inflammatory markers are cross-sectionally and longitudinally associated with neuropsychological indicators of early ischemia and Alzheimer's disease. Methods: Framingham Offspring Study participants, free of clinical stroke or dementia (n = 1,878; 60 +/- 9 years; 54% women), underwent neuropsychological assessment and ascertainment of 11 inflammatory markers. Follow-up neuropsychological assessments (6.3 +/- 1.0 years) were conducted on 1,352 of the original 1,878 participants. Results: Multivariable linear regression related the inflammatory markers to cross-sectional performance and longitudinal change in neuropsychological performances. Secondary models included a twelfth factor, tumor necrosis factor-alpha (TNF-alpha), available on a subset of the sample (n = 1,393 cross-sectional; n = 1,213 longitudinal). Results suggest a few modest cross-sectional inflammatory and neuropsychological associations, particularly for tests assessing visual organization (C-reactive protein, p = 0.007), and a few modest relations between inflammatory markers and neuropsychological change, particularly for executive functioning (TNF-alpha, p = 0.004). Secondary analyses suggested that inflammatory markers were cross-sectionally (TNF-alpha, p = 0.004) related to reading performance. Conclusions: Our findings are largely negative, but suggest that specific inflammatory markers may have limited associations with poorer cognition and reading performance among community-dwelling adults. Because of multiple testing concerns, our limited positive findings are offered as hypothesis generating and require replication in other studies. Copyright (C) 2011 S. Karger AG, Basel C1 [Jefferson, Angela L.] Boston Univ, Sch Med, Alzheimers Dis Ctr, Boston, MA 02118 USA. [Massaro, Joseph M.; Beiser, Alexa S.; Larson, Martin G.; Benjamin, Emelia J.] Boston Univ, Sch Publ Hlth, Boston, MA USA. [Massaro, Joseph M.; Beiser, Alexa S.; Seshadri, Sudha; Larson, Martin G.; Wolf, Philip A.; Au, Rhoda; Benjamin, Emelia J.] NHLBI, Framingham Heart Study, Framingham, MA USA. RP Jefferson, AL (reprint author), Boston Univ, Sch Med, Alzheimers Dis Ctr, 72 E Concord St,B-7800, Boston, MA 02118 USA. EM angelaj@bu.edu OI Massaro, Joseph/0000-0002-2682-4812; Larson, Martin/0000-0002-9631-1254; Seshadri, Sudha/0000-0001-6135-2622; Au, Rhoda/0000-0001-7742-4491; Benjamin, Emelia/0000-0003-4076-2336; Beiser, Alexa/0000-0001-8551-7778 NR 49 TC 18 Z9 18 U1 0 U2 4 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 0251-5350 J9 NEUROEPIDEMIOLOGY JI Neuroepidemiology PY 2011 VL 37 IS 1 BP 21 EP 30 DI 10.1159/000328864 PG 10 WC Public, Environmental & Occupational Health; Clinical Neurology SC Public, Environmental & Occupational Health; Neurosciences & Neurology GA 811NF UT WOS:000294217300004 PM 21757961 ER PT J AU Granert, O Peller, M Gaser, C Groppa, S Hallett, M Knutzen, A Deuschl, G Zeuner, KE Siebner, HR AF Granert, Oliver Peller, Martin Gaser, Christian Groppa, Sergiu Hallett, Mark Knutzen, Arne Deuschl, Guenther Zeuner, Kirsten E. Siebner, Hartwig R. TI Manual activity shapes structure and function in contralateral human motor hand area SO NEUROIMAGE LA English DT Article DE Cortical plasticity; Focal dystonia; Human motor cortex; Immobilization; Magnetic resonance imaging; Motor training; Transcranial magnetic stimulation; Voxel based morphometry ID TRANSCRANIAL MAGNETIC STIMULATION; VOXEL-BASED MORPHOMETRY; WRITERS CRAMP; WHITE-MATTER; LIMB IMMOBILIZATION; CORTEX EXCITABILITY; HUNTINGTONS-DISEASE; ADULT CORTEX; BRAIN; PLASTICITY AB From longitudinal voxel-based morphometry (VBM) studies we know that relatively short periods of training can increase regional grey matter volume in trained cortical areas. In 14 right-handed patients with writer's cramp, we employed VBM to test whether suppression (i.e., immobilization) or enhancement (i.e., training) of manual activity lead to opposing changes in grey matter in the contralateral primary motor hand area (M1(HAND)). We additionally used transcranial magnetic stimulation (TMS) to evaluate concurrent changes in regional excitability. Patients were recruited from a clinical trial which was designed to improve handwriting-associated dystonia. Initially the dystonic hand was immobilized for 4 weeks with the intention to reverse faulty plasticity. After immobilization, patients accomplished a motor re-training for 8 weeks. T1-weighted MRIs of the whole brain and single-pulse TMS measurements of the resting motor threshold (RMT) were performed every 4 weeks. Immobilization of the right hand resulted in a relative grey matter decrease in the contralateral left M1(HAND) along with a decrease in corticomotor excitability as indexed by an increase in RMT. Subsequent training reversed the effects of immobilization, causing an increase in regional grey matter density and excitability of left M1(HAND). The relative changes in grey matter correlated with the relative shifts in RMT. This prospective within-subject VBM study in task-specific hand dystonia shows that the grey matter density of M1(HAND) is dynamically shaped by the level of manual activity. This bi-directional structural plasticity is functionally relevant as local grey matter changes are mirrored by changes in regional excitability. (C) 2010 Elsevier Inc. All rights reserved. C1 [Granert, Oliver; Peller, Martin; Groppa, Sergiu; Knutzen, Arne; Deuschl, Guenther; Zeuner, Kirsten E.; Siebner, Hartwig R.] Univ Kiel, Dept Neurol, D-24105 Kiel, Germany. [Gaser, Christian] Univ Jena, Dept Psychiat, Jena, Germany. [Hallett, Mark] Natl Inst Neurol Disorders & Stroke, Human Motor Control Sect, Med Neurol Branch, NIH, Bethesda, MD USA. [Siebner, Hartwig R.] NeuroImageNord, Hamburg, Germany. [Siebner, Hartwig R.] Univ Copenhagen, Hvidovre Hosp, Danish Res Ctr Magnet Resonance, DK-2650 Hvidovre, Denmark. [Siebner, Hartwig R.] Univ Copenhagen, Dept Neurol Psychiat & Senses, Fac Med, Copenhagen, Denmark. RP Granert, O (reprint author), Univ Kiel, Dept Neurol, Arnold Heller Str 3,Haus 41, D-24105 Kiel, Germany. EM o.granert@neurologie.uni-kiel.de RI Gaser, Christian/F-5103-2010; Groppa, Sergiu/G-4606-2014; Deuschl, Gunther/A-7986-2010; Siebner, Hartwig/G-4052-2016; OI Gaser, Christian/0000-0002-9940-099X; Granert, Oliver/0000-0002-0656-1023 FU Deutsche Forschungsgemeinschaft [DE 438/7, 7-2]; BMBF [01GO 0511] FX This study was supported by a project grant from the Deutsche Forschungsgemeinschaft (DE 438/7 and 7-2). H.S. was funded by a structural grant of the BMBF to Neuroimage Nord (grant nr. 01GO 0511). We greatly appreciate the patients for participating in this study. We would like to thank Dirk Dressler, Department of Neurology at the Hannover Medical School, Alexander Munchau, Department of Neurology at the University of Hamburg, Lars Timmermann, Department of Neurology, University of Cologne and Markus Butz, Department of Neurology, University of Dusseldorf for referring patients to us. NR 64 TC 51 Z9 51 U1 2 U2 9 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1053-8119 J9 NEUROIMAGE JI Neuroimage PD JAN 1 PY 2011 VL 54 IS 1 BP 32 EP 41 DI 10.1016/j.neuroimage.2010.08.013 PG 10 WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA 675IY UT WOS:000283825000006 PM 20708692 ER PT J AU Zhang, XC Salmeron, BJ Ross, TJ Geng, XJ Yang, YH Stein, EA AF Zhang, Xiaochu Salmeron, Betty Jo Ross, Thomas J. Geng, Xiujuan Yang, Yihong Stein, Elliot A. TI Factors underlying prefrontal and insula structural alterations in smokers SO NEUROIMAGE LA English DT Article ID WHITE-MATTER INTEGRITY; NICOTINE DEPENDENCE; CIGARETTE-SMOKING; SPATIAL STATISTICS; COCAINE DEPENDENCE; GRAY-MATTER; MIDDLE-AGE; MR-IMAGES; IN-VIVO; DIFFUSION AB Based upon previous reports of alterations in white matter integrity and gray matter density in smokers, we examined these markers in a large, well-matched sample of smokers and non-smokers. We further investigated the effect of heavy cigarette exposure by using pack-years and the effects of two relatively stable, highly heritable traits in smokers (Fagerstrom Test of Nicotine Dependence (FIND), a measure of severity of nicotine dependence and Toronto Alexithymia Scale (TAS-20), a stable personality trait related to smoking). Forty-eight nicotine-dependent subjects and 48 matched controls were included in the analyses, with smokers also subdivided into high/low dependence and high/low pack-years smokers. White matter integrity (fractional anisotropy (FA)) and gray matter density (voxel-based morphometry (VBM)) were measured and compared across groups. Gray matter density was lower in left prefrontal cortex (PFC) in high pack-years smokers and was inversely related to pack-years. In contrast, left insular cortex gray matter density was higher in smokers and associated with TAS-20 total score and with difficulty-identifying-feelings factor. Further, the most highly dependent smokers showed lower prefrontal FA, which was negatively correlated with FEND. There was no correlation between pack-years and FIND in our smoker population. These data suggest chronic tobacco use is correlated with prefrontal gray matter damage, while differences in insula gray matter and PFC white matter appear to reflect stable and heritable differences between smokers and non-smokers. Published by Elsevier Inc. C1 [Zhang, Xiaochu; Salmeron, Betty Jo; Ross, Thomas J.; Geng, Xiujuan; Yang, Yihong; Stein, Elliot A.] Natl Inst Drug Abuse, Neuroimaging Res Branch, Intramural Res Program, NIH, Baltimore, MD 21224 USA. RP Stein, EA (reprint author), Natl Inst Drug Abuse, Neuroimaging Res Branch, Intramural Res Program, NIH, Baltimore, MD 21224 USA. EM estein@mail.nih.gov RI Ross, Thomas/B-7469-2008; Geng, Xiujuan/I-3852-2012; Zhang, Xiaochu/O-9592-2014; Salmeron, Betty Jo/M-1793-2016 OI Ross, Thomas/0000-0002-7745-3572; Zhang, Xiaochu/0000-0002-7541-0130; Salmeron, Betty Jo/0000-0003-1699-9333 FU National Institute on Drug Abuse, NIH FX This research was supported by the Intramural Research Program of the National Institute on Drug Abuse, NIH. We thank Kimberly Modo and Loretta Spurgeon for their assistance in the conduct of the study and Mary Pfeiffer for editing assistance. NR 63 TC 82 Z9 85 U1 2 U2 13 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1053-8119 J9 NEUROIMAGE JI Neuroimage PD JAN 1 PY 2011 VL 54 IS 1 BP 42 EP 48 DI 10.1016/j.neuroimage.2010.08.008 PG 7 WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA 675IY UT WOS:000283825000007 PM 20699124 ER PT J AU Zhang, XC Salmeron, BJ Ross, TJ Gu, H Geng, XJ Yang, YH Stein, EA AF Zhang, Xiaochu Salmeron, Betty Jo Ross, Thomas J. Gu, Hong Geng, Xiujuan Yang, Yihong Stein, Elliot A. TI Anatomical differences and network characteristics underlying smoking cue reactivity SO NEUROIMAGE LA English DT Article DE Smoking cue; Anatomical; ASL; DTI; VBM; Resting state functional connectivity ID CEREBRAL-BLOOD-FLOW; STRIATUM/NUCLEUS ACCUMBENS ACTIVATION; STATE FUNCTIONAL CONNECTIVITY; COGNITIVE CONTROL; NICOTINE DEPENDENCE; CIGARETTE-SMOKING; PROCESSING MODEL; NEURAL ACTIVITY; BRAIN ACTIVITY; COCAINE AB A distributed network of brain regions is linked to drug-related cue responding. However, the relationships between smoking cue-induced phasic activity and possible underlying differences in brain structure, tonic neuronal activity and connectivity between these brain areas are as yet unclear. Twenty-two smokers and 22 controls viewed smoking-related and neutral pictures during a functional arterial spin labeling scanning session. T1, resting functional, and diffusion tensor imaging data were also collected. Six brain areas, dorsal lateral prefrontal cortex (dIPFC), dorsal medial prefrontal cortex (dmPFC), dorsal anterior cingulate cortex/cingulate cortex, rostral anterior cingulate cortex (rACC), occipital cortex, and insula/operculum, showed significant smoking cue-elicited activity in smokers when compared with controls and were subjected to secondary analysis for resting state functional connectivity (rsFC). structural, and tonic neuronal activity. rsFC strength between rACC and dIPFC was positively correlated with the cue-elicited activity in dIPFC. Similarly, rsFC strength between dIPFC and dmPFC was positively correlated with the cue-elicited activity in dmPFC while rsFC strength between dmPFC and insula/operculum was negatively correlated with the cue-elicited activity in both dmPFC and insula/operculum, suggesting these brain circuits may facilitate the response to the salient smoking cues. Further, the gray matter density in dIPFC was decreased in smokers and correlated with cue-elicited activity in the same brain area, suggesting a neurobiological mechanism for the impaired cognitive control associated with drug use. Taken together, these results begin to address the underlying neurobiology of smoking cue salience, and may speak to novel treatment strategies and targets for therapeutic interventions. Published by Elsevier Inc. C1 [Zhang, Xiaochu; Salmeron, Betty Jo; Ross, Thomas J.; Gu, Hong; Geng, Xiujuan; Yang, Yihong; Stein, Elliot A.] Natl Inst Drug Abuse, Neuroimaging Res Branch, Intramural Res Program, NIH, Baltimore, MD 21224 USA. RP Stein, EA (reprint author), Natl Inst Drug Abuse, Neuroimaging Res Branch, Intramural Res Program, NIH, Baltimore, MD 21224 USA. EM estein@mail.nih.gov RI Ross, Thomas/B-7469-2008; Geng, Xiujuan/I-3852-2012; Zhang, Xiaochu/O-9592-2014; Salmeron, Betty Jo/M-1793-2016 OI Ross, Thomas/0000-0002-7745-3572; Zhang, Xiaochu/0000-0002-7541-0130; Salmeron, Betty Jo/0000-0003-1699-9333 FU National Institute on Drug Abuse, NIH FX This research was supported by the Intramural Research Program of the National Institute on Drug Abuse, NIH. We thank Kimberly Modo and Loretta Spurgeon for their assistance in the conduct of some of the studies reported herein and Mary Pfeiffer for editing assistance. The authors reported no financial interests or potential conflicts of interest. NR 74 TC 43 Z9 48 U1 0 U2 10 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1053-8119 J9 NEUROIMAGE JI Neuroimage PD JAN 1 PY 2011 VL 54 IS 1 BP 131 EP 141 DI 10.1016/j.neuroimage.2010.07.063 PG 11 WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA 675IY UT WOS:000283825000016 PM 20688176 ER PT J AU Strobel, A Zimmermann, J Schmitz, A Reuter, M Lis, S Windmann, S Kirsch, P AF Strobel, Alexander Zimmermann, Jan Schmitz, Anja Reuter, Martin Lis, Stefanie Windmann, Sabine Kirsch, Peter TI Beyond revenge: Neural and genetic bases of altruistic punishment SO NEUROIMAGE LA English DT Article DE Altruistic punishment; Functional magnetic resonance imaging; Nucleus accumbens; Nucleus caudatus; Catechol-O-methyltransferase; Polymorphism ID ECONOMIC DECISION-MAKING; PREFRONTAL CORTEX; ULTIMATUM GAME; REWARD; DOPAMINE; BRAIN; NEUROBIOLOGY; POLYMORPHISM; SENSITIVITY; RECIPROCITY AB It is still debated how altruistic punishment as one form of strong reciprocity has established during evolution and which motives may underlie such behavior. Recent neuroscientific evidence on the activation of brain reward regions during altruistic punishment in two-person one-shot exchange games suggests satisfaction through the punishment of norm violations as one underlying motive. In order to address this issue in more detail, we used fMRI during a one-shot economic exchange game that warrants strong reciprocity by introducing a third party punishment condition wherein revenge is unlikely to play a role. We report here that indeed, reward regions such as the nucleus accumbens showed punishment-related activation. Moreover, we provide preliminary evidence that genetic variation of dopamine turnover impacts similarly on punishment-related nucleus accumbens activation during both first person and third party punishment. The overall pattern of results suggests a common cognitive-affective-motivational network as the driving force for altruistic punishment, with only quantitative differences between first person and third party perspectives. (C) 2010 Elsevier Inc. All rights reserved. C1 [Strobel, Alexander] Tech Univ Dresden, Dept Psychol, D-01062 Dresden, Germany. [Strobel, Alexander; Zimmermann, Jan; Windmann, Sabine] Goethe Univ Frankfurt, Inst Psychol, D-6000 Frankfurt, Germany. [Zimmermann, Jan] Maastricht Univ, Dept Cognit Neurosci, Maastricht, Netherlands. [Schmitz, Anja] Univ Giessen, Inst Psychol, D-35390 Giessen, Germany. [Schmitz, Anja] NIMH, NIH, Bethesda, MD 20892 USA. [Reuter, Martin] Univ Bonn, Inst Psychol, D-5300 Bonn, Germany. [Lis, Stefanie; Kirsch, Peter] Univ Giessen, Ctr Psychiat, D-35390 Giessen, Germany. [Kirsch, Peter] Cent Inst Mental Hlth, Dept Clin Psychol, D-68159 Mannheim, Germany. RP Strobel, A (reprint author), Tech Univ Dresden, Dept Psychol, Mommsenstr 13, D-01062 Dresden, Germany. EM alex.strobel@gmx.de; peter.kirsch@zi-mannheim.de RI Strobel, Alexander/I-5026-2015; OI Strobel, Alexander/0000-0002-9426-5397; Zimmermann, Jan/0000-0003-3345-6074; Kirsch, Peter/0000-0002-0817-1248; Lis, Stefanie/0000-0002-8051-2756 NR 42 TC 56 Z9 57 U1 11 U2 73 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1053-8119 J9 NEUROIMAGE JI Neuroimage PD JAN 1 PY 2011 VL 54 IS 1 BP 671 EP 680 DI 10.1016/j.neuroimage.2010.07.051 PG 10 WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA 675IY UT WOS:000283825000069 PM 20673803 ER PT J AU Kateb, B Chiu, K Black, KL Yamamoto, V Khalsa, B Ljubimova, JY Ding, H Patil, R Portilla-Arias, JA Modo, M Moore, DF Farahani, K Okun, MS Prakash, N Neman, J Ahdoot, D Grundfest, W Nikzad, S Heiss, JD AF Kateb, Babak Chiu, Katherine Black, Keith L. Yamamoto, Vicky Khalsa, Bhavraj Ljubimova, Julia Y. Ding, Hui Patil, Rameshwar Portilla-Arias, Jose Antonio Modo, Mike Moore, David F. Farahani, Keyvan Okun, Michael S. Prakash, Neal Neman, Josh Ahdoot, Daniel Grundfest, Warren Nikzad, Shouleh Heiss, John D. TI Nanoplatforms for constructing new approaches to cancer treatment, imaging, and drug delivery: What should be the policy? SO NEUROIMAGE LA English DT Article DE Nanoplatforms; Nanotechnology; Image-guided therapy; Nanomedicine; Nanoneurosurgery; Nanostructures; Contrast agents; Nanoparticles; Nanotechnology policy; Nano-radiology; Nano-neuroscience; Nano-neurology ID NEPHROGENIC SYSTEMIC FIBROSIS; IRON-OXIDE NANOPARTICLES; FUNCTIONALIZED CARBON NANOTUBES; MAGNETIC-RESONANCE TRACKING; BLOOD-BRAIN-BARRIER; MRI CONTRAST AGENTS; PLURONIC((R)) BLOCK-COPOLYMERS; SEMICONDUCTOR QUANTUM DOTS; VX-2 RABBIT TUMORS; SIALYL-LEWIS-X AB Nanotechnology is the design and assembly of submicroscopic devices called nanoparticles, which are 1-100 nm in diameter. Nanomedicine is the application of nanotechnology for the diagnosis and treatment of human disease. Disease-specific receptors on the surface of cells provide useful targets for nanoparticles. Because nanoparticles can be engineered from components that (1) recognize disease at the cellular level, (2) are visible on imaging studies, and (3) deliver therapeutic compounds, nanotechnology is well suited for the diagnosis and treatment of a variety of diseases. Nanotechnology will enable earlier detection and treatment of diseases that are best treated in their initial stages, such as cancer. Advances in nanotechnology will also spur the discovery of new methods for delivery of therapeutic compounds, including genes and proteins, to diseased tissue. A myriad of nanostructured drugs with effective site-targeting can be developed by combining a diverse selection of targeting, diagnostic, and therapeutic components. Incorporating immune target specificity with nanostructures introduces a new type of treatment modality, nano-immunochemotherapy, for patients with cancer. In this review, we will discuss the development and potential applications of nanoscale platforms in medical diagnosis and treatment. To impact the care of patients with neurological diseases, advances in nanotechnology will require accelerated translation to the fields of brain mapping, CNS imaging, and nanoneurosurgery. Advances in nanoplatform, nano-imaging, and nano-drug delivery will drive the future development of nanomedicine, personalized medicine, and targeted therapy. We believe that the formation of a science, technology, medicine law-healthcare policy (STML) hub/center, which encourages collaboration among universities, medical centers, US government, industry, patient advocacy groups, charitable foundations, and philanthropists, could significantly facilitate such advancements and contribute to the translation of nanotechnology across medical disciplines. (C) 2010 Elsevier Inc. All rights reserved. C1 [Kateb, Babak; Moore, David F.; Okun, Michael S.; Prakash, Neal; Grundfest, Warren; Nikzad, Shouleh; Heiss, John D.] IBMISPS, W Hollywood, CA 90046 USA. [Kateb, Babak; Ahdoot, Daniel; Grundfest, Warren; Nikzad, Shouleh] Brain Mapping Fdn, W Hollywood, CA 90046 USA. [Kateb, Babak] Univ So Calif, Viterbi Sch Engn, Los Angeles, CA 90089 USA. [Kateb, Babak; Yamamoto, Vicky; Nikzad, Shouleh] Univ So Calif, Keck Sch Med, Los Angeles, CA 90033 USA. [Kateb, Babak; Black, Keith L.; Ljubimova, Julia Y.; Ding, Hui; Patil, Rameshwar; Portilla-Arias, Jose Antonio] Cedars Sinai Med Ctr, Maxine Dunitz Neurosurg Inst, Los Angeles, CA 90048 USA. [Chiu, Katherine; Khalsa, Bhavraj] Univ Calif Irvine, Sch Med, Irvine, CA 92697 USA. [Moore, David F.] Walter Reed Army Med Ctr, DVBIC, Washington, DC 20307 USA. [Modo, Mike] Kings Coll London, London WC2R 2LS, England. [Neman, Josh; Grundfest, Warren] Univ Calif Los Angeles, David Geffen Sch Med, Los Angeles, CA 90095 USA. [Okun, Michael S.] Univ Florida, Movement Disorders Ctr, Dept Neurol, Gainesville, FL 32610 USA. [Okun, Michael S.] Univ Florida, Movement Disorders Ctr, Dept Neurosurg, Gainesville, FL 32610 USA. [Prakash, Neal] Univ Hawaii, John A Burns Sch Med, Manoa, HI 96813 USA. [Farahani, Keyvan] NCI, Bethesda, MD 20892 USA. [Heiss, John D.] NINDS, Bethesda, MD 20824 USA. [Nikzad, Shouleh] CALTECH, Jet Prop Lab, Pasadena, CA 91109 USA. RP Kateb, B (reprint author), IBMISPS, 8159 Santa Monica Blvd,Suite 200, W Hollywood, CA 90046 USA. EM Bkateb@ibmisps.org RI Modo, Michel/E-5170-2012; Farahani, Keyvan/G-9069-2012; PORTILLA-ARIAS, JOSE/C-3223-2008; OI PORTILLA-ARIAS, JOSE/0000-0003-1105-1842; Khalsa, Bhavraj/0000-0003-0915-931X; Okun, Michael/0000-0002-6247-9358; Heiss, John/0000-0002-3890-0165; Modo, Michel/0000-0003-4436-735X FU NIH/NCI [R01 CA123495]; NIBIB [1 P20 EB007076-01] FX We would like to specially thank Dr. Eggehard Holler for his contribution to the paper. Our thanks and appreciation to Dr. Nakissa Sadrieh for her permission to include the table on FDA-approved drugs in the nanometer scale. We would also like to acknowledge Julia Ljubimova and Mike Modo's grant support from the NIH/NCI R01 CA123495 grant and NIBIB (Quantum Grant-1 P20 EB007076-01), respectively. Dr. Modo's NIBIB Quantum Grant is directed towards tissue engineering and brain research (PEG-based hydrogels, etc.). We acknowledge Dr. Behnam Badie for his editorial contributions and Rohit Majumdar and Adrian Au for their time and help in conducting the literature search. This work is also made possible through a generous contribution of the Brain Mapping Foundation. The contents of this paper are solely the responsibility of the authors and represent the official position of the IBMISP Society. The contents do not represent the official views of NINDS/NIH and NCI/NIH. NR 237 TC 65 Z9 67 U1 10 U2 77 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 PY 2011 VL 54 SU 1 BP S106 EP S124 DI 10.1016/j.neuroimage.2010.01.105 PG 19 WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA 813ZF UT WOS:000294408600016 PM 20149882 ER PT J AU Mays, J Butts, CL AF Mays, Jacqueline Butts, Cherie L. TI Intercommunication between the Neuroendocrine and Immune Systems: Focus on Myasthenia Gravis SO NEUROIMMUNOMODULATION LA English DT Article DE Autoimmunity; Thymoma; Acetylcholine receptor; Steroid hormones; Immune system ID RECEPTOR ALPHA-SUBUNIT; ACETYLCHOLINE-RECEPTOR; NEUROMUSCULAR-JUNCTION; CLASS-II; T-CELLS; ANTIBODIES; ESTROGEN; EXPRESSION; PREGNANCY; THYMOMA AB Crosstalk exists between the nervous, endocrine, and immune systems, and perturbations in these interactions have been associated with disease. This includes production of neuroendocrine factors that alter immune system activity and increase susceptibility to or severity of immune-related conditions, such as myasthenia gravis (MG) - a T-cell-dependent, B-cell-mediated autoimmune disorder. MG results from impairment of transmission to the neuromuscular junction and involves the thymus - especially in early-onset disease, but the exact mechanism by which the thymus impacts disease is unclear. MG afflicts millions of individuals worldwide each year, and both men and women can develop symptoms. However, prevalence and age of onset differs between men and women. Women exhibit higher incidence and earlier age of onset compared to men, and disease fluctuates during pregnancy. This suggests that sex hormones play a role in influencing disease outcome. In this review, we will consider what is known about the manifestation of MG, theories on how different forms of MG are influenced or alleviated by steroid hormones, current treatment options, and what measures could be important to consider in the future. Copyright (C) 2011 S. Karger AG, Basel C1 [Butts, Cherie L.] US FDA, Immunol Lab, Div Therapeut Prot, Off Biotechnol Prod,Ctr Drug Evaluat & Res, Bethesda, MD 20892 USA. [Mays, Jacqueline] NIAID, Viral Dis Lab, NIH, Bethesda, MD 20892 USA. RP Butts, CL (reprint author), US FDA, Immunol Lab, Div Therapeut Prot, Off Biotechnol Prod,Ctr Drug Evaluat & Res, 8800 Rockville Pike,HFD 122,Bldg 29A,Room 3B19, Bethesda, MD 20892 USA. EM cherie.butts@fda.hhs.gov NR 57 TC 3 Z9 3 U1 0 U2 1 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 1021-7401 J9 NEUROIMMUNOMODULAT JI Neuroimmunomodulation PY 2011 VL 18 IS 5 BP 320 EP 327 DI 10.1159/000329491 PG 8 WC Endocrinology & Metabolism; Immunology; Neurosciences SC Endocrinology & Metabolism; Immunology; Neurosciences & Neurology GA 823XT UT WOS:000295162000008 PM 21952684 ER PT B AU Montes, J Kaufmann, P AF Montes, Jacqueline Kaufmann, Petra BE Tawil, RN Venance, S TI Spinal Muscular Atrophy SO NEUROMUSCULAR DISORDERS SE Neurology in Practice LA English DT Article; Book Chapter ID CONSENSUS STATEMENT; CLASSIFICATION; SMA; SURVIVAL; STANDARD; TYPE-1; MOUSE; CARE C1 [Montes, Jacqueline] Columbia Univ, Dept Neurol, SMA Clin Res Ctr, New York, NY 10027 USA. [Kaufmann, Petra] NINDS, NIH, Bethesda, MD 20892 USA. RP Montes, J (reprint author), Columbia Univ, Dept Neurol, SMA Clin Res Ctr, New York, NY 10027 USA. NR 15 TC 0 Z9 0 U1 0 U2 1 PU WILEY-BLACKWELL PI CHICHESTER PA THE ATRIUM, SOUTHERN GATE, CHICHESTER, WEST SUSSEX PO19 8SQ, ENGLAND BN 978-1-119-97330-0; 978-0-470-65456-9 J9 NEUROL PRACT PY 2011 BP 229 EP 235 D2 10.1002/9781119973331 PG 7 WC Clinical Neurology SC Neurosciences & Neurology GA BA7AV UT WOS:000337348200032 ER PT J AU Alushin, GM Jane, D Mayer, ML AF Alushin, Gregory M. Jane, David Mayer, Mark L. TI Binding site and ligand flexibility revealed by high resolution crystal structures of GluK1 competitive antagonists SO NEUROPHARMACOLOGY LA English DT Article DE Glutamate receptors; Crystal structure; Conformational flexibility; Halogen bond ID KAINATE RECEPTOR ANTAGONIST; PARTIAL AGONIST ACTION; GLUR2 AMPA RECEPTOR; GLUTAMATE-RECEPTOR; PHARMACOLOGICAL CHARACTERIZATION; NMDA RECEPTORS; HALOGEN BONDS; DOMOIC ACID; CORE DIMER; IN-VIVO AB The availability of crystal structures for the ligand binding domains of ionotropic glutamate receptors, combined with their key role in synaptic function in the normal and diseased brain, offers a unique selection of targets for pharmaceutical research compared to other drug targets for which the atomic structure of the ligand binding site is not known. Currently only a few antagonist structures have been solved, and these reveal ligand specific conformational changes that hinder rational drug design. Here we report high resolution crystal structures for three kainate receptor GluK1 antagonist complexes which reveal new and unexpected modes of binding, highlighting the continued need for experimentally determined receptor-ligand complexes. Published by Elsevier Ltd. C1 [Alushin, Gregory M.; Mayer, Mark L.] NICHD, Lab Cellular & Mol Neurophysiol, Porter Neurosci Res Ctr, NIH,DHHS, Bethesda, MD 20892 USA. [Jane, David] Univ Bristol, Dept Pharmacol, MRC Ctr Synapt Plast, Bristol BS8 1TD, Avon, England. RP Mayer, ML (reprint author), NICHD, Lab Cellular & Mol Neurophysiol, Porter Neurosci Res Ctr, NIH,DHHS, Bldg 35,Room 3B 1002,35 Lincoln Dr, Bethesda, MD 20892 USA. EM mlm@helix.nih.gov RI Mayer, Mark/H-5500-2013 FU U.S. Department of Energy, Office of Science, Office of Basic Energy Sciences [W-31-109-Eng-38]; NICHD, NIH, DHHS; BBSRC FX GMA was a postbac IRTA fellow of the NIH. Synchrotron diffraction data was collected at Southeast Regional Collaborative Access Team (SER-CAT) 22-ID beamline at the Advanced Photon Source, Argonne National Laboratory. Supporting institutions may be found at www.ser-cat.org/members.html. Use of the Advanced Photon Source was supported by the U.S. Department of Energy, Office of Science, Office of Basic Energy Sciences, under Contract No. W-31-109-Eng-38. This work was supported by the intramural research program of NICHD, NIH, DHHS. Work leading to the synthesis of UBP315 and UBP318 was supported by the BBSRC. We thank Dr. David Bleakman for the gift of LY466195 and Dr. Jinjin Zhang for comments on the manuscript. NR 52 TC 14 Z9 14 U1 2 U2 5 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0028-3908 J9 NEUROPHARMACOLOGY JI Neuropharmacology PD JAN PY 2011 VL 60 IS 1 BP 126 EP 134 DI 10.1016/j.neuropharm.2010.06.002 PG 9 WC Neurosciences; Pharmacology & Pharmacy SC Neurosciences & Neurology; Pharmacology & Pharmacy GA 703PA UT WOS:000285989500015 PM 20558186 ER PT J AU Bisgaard, H Larsen, MAB Mazier, S Beuming, T Newman, AH Weinstein, H Shi, L Loland, CJ Gether, U AF Bisgaard, Heidi Larsen, M. Andreas B. Mazier, Sonia Beuming, Thijs Newman, Amy Hauck Weinstein, Hare Shi, Lei Loland, Claus J. Gether, Ulrik TI The binding sites for benztropines and dopamine in the dopamine transporter overlap SO NEUROPHARMACOLOGY LA English DT Article DE Neurotransmitter:sodium symporters; Monoamine transporters; Dopamine transporter; Cocaine; Molecular modeling; Mutagenesis ID HUMAN SEROTONIN TRANSPORTER; NEUROTRANSMITTER TRANSPORTERS; UPTAKE INHIBITORS; POPULATION PHARMACOKINETICS; MONOAMINE TRANSPORTERS; CONFORMATIONAL-CHANGES; BRAIN DISTRIBUTION; BACTERIAL HOMOLOG; COCAINE BINDING; ANALOGS AB Analogs of benztropines (BZTs) are potent inhibitors of the dopamine transporter (DAT) but are less effective than cocaine as behavioral stimulants. As a result, there have been efforts to evaluate these compounds as leads for potential medication for cocaine addiction. Here we use computational modeling together with site-directed mutagenesis to characterize the binding site for BZTs in DAT. Docking into molecular models based on the structure of the bacterial homolog LeuT supported a BZT binding site that overlaps with the substrate-binding pocket. In agreement, mutations of residues within the pocket, including(2) Val152(3.46) to Ala or Ile, Ser422(8.60) to Ala and Asn157(3.51) to Cys or Ala, resulted in decreased affinity for BZT and the analog JHW007, as assessed in [(3)H]dopamine uptake inhibition assays and/or [(3)H] CFT competition binding assay. A putative polar interaction of one of the phenyl ring fluorine substituents in JHW007 with Asn157(3.51) was used as a criterion for determining likely binding poses and establish a structural context for the mutagenesis findings. The analysis positioned the other fluorine-substituted phenyl ring of JHW007 in close proximity to Ala479(10.51)/Ala480(10.52) in transmembrane segment (TM) 10. The lack of such an interaction for BZT led to a more tilted orientation, as compared to JHW007, bringing one of the phenyl rings even closer to Ala479(10.51)/Ala480(10.52). Mutation of Ala479(10.51) and Ala480(10.52) to valines supported these predictions with a larger decrease in the affinity for Bit than for JHW007. Summarized, our data suggest that BZTs display a classical competitive binding mode with binding sites overlapping those of cocaine and dopamine. (C) 2010 Elsevier Ltd. All rights reserved. C1 [Gether, Ulrik] Univ Copenhagen, Panum Inst, Dept Neurosci & Pharmacol,Mol Neuropharmacol Lab, Mol Neuropharmacol Grp,Fac Hlth Sci, DK-2200 Copenhagen N, Denmark. [Mazier, Sonia; Weinstein, Hare; Shi, Lei] Cornell Univ, Weill Cornell Med Coll, Dept Physiol & Biophys, New York, NY 10065 USA. [Beuming, Thijs] Schrodinger Inc, New York, NY 10036 USA. [Weinstein, Hare; Shi, Lei] Cornell Univ, Weill Cornell Med Coll, HRH Prince Alwaleed Bin Talal Bin Abdulaziz Alsau, New York, NY 10065 USA. [Newman, Amy Hauck] NIDA, Med Chem Sect, Medicat Discovery Res Branch, Intramural Res Program,Dept Hlth & Human Serv,NIH, Baltimore, MD 21224 USA. RP Gether, U (reprint author), Univ Copenhagen, Panum Inst, Dept Neurosci & Pharmacol,Mol Neuropharmacol Lab, Mol Neuropharmacol Grp,Fac Hlth Sci, Bldg 18-6,Blegdamsvej 3, DK-2200 Copenhagen N, Denmark. EM gether@sund.ku.dk RI Loland, Claus/E-5975-2014; Bisgaard, Hans/N-4761-2016; OI Loland, Claus/0000-0002-1773-1446; Bisgaard, Hans/0000-0003-4131-7592; Gether, Ulrik/0000-0002-0020-3807 FU National Institute of Health [P01 DA12408, R00 DA023694]; NIDA; Danish Health Science Research Council; Lundbeck Foundation; Novo Nordisk Foundation; Maersk Foundation FX We thank Pia Elsman for technical assistance and Jianjing Cao for synthesizing the BZT analogs used in this study. The work was supported in part by the National Institute of Health Grants P01 DA12408 (HW and UG), R00 DA023694 (LS), the NIDA-Intramural Research Program (A.H.N), the Danish Health Science Research Council (CJL and UG), the Lundbeck Foundation (CJL and UG), the Novo Nordisk Foundation (CJL and UG), and the Maersk Foundation (CJL). NR 49 TC 27 Z9 27 U1 0 U2 5 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0028-3908 J9 NEUROPHARMACOLOGY JI Neuropharmacology PD JAN PY 2011 VL 60 IS 1 BP 182 EP 190 DI 10.1016/j.neuropharm.2010.08.021 PG 9 WC Neurosciences; Pharmacology & Pharmacy SC Neurosciences & Neurology; Pharmacology & Pharmacy GA 703PA UT WOS:000285989500020 PM 20816875 ER PT J AU Petrides, G Tobias, KG Kellner, CH Rudorfer, MV AF Petrides, Georgios Tobias, Kristen G. Kellner, Charles H. Rudorfer, Matthew V. TI Continuation and Maintenance Electroconvulsive Therapy for Mood Disorders: Review of the Literature SO NEUROPSYCHOBIOLOGY LA English DT Review DE Electroconvulsive therapy; Continuation electroconvulsive therapy; Maintenance electroconvulsive therapy; Mood disorders; Review ID RANDOMIZED CONTROLLED-TRIAL; RESISTANT BIPOLAR DISORDER; LIFE PSYCHOTIC DEPRESSION; RELAPSE PREVENTION; CATATONIC SCHIZOPHRENIA; PARKINSONS-DISEASE; CONVULSIVE THERAPY; MAJOR DEPRESSION; REFRACTORY MANIA; ELDERLY-PATIENTS AB Background: Electroconvulsive therapy (ECT) is a highly effective treatment for mood disorders. Continuation ECT (C-ECT) and maintenance ECT (M-ECT) are required for many patients suffering from severe and recurrent forms of mood disorders. This is a review of the literature regarding C- and M-ECT. Methods: We conducted a computerized search using the words continuation ECT, maintenance ECT, depression, mania, bipolar disorder and mood disorders. We report on all articles published in the English language from 1998 to 2009. Results: We identified 32 reports. There were 24 case reports and retrospective reviews on 284 patients. Two of these reports included comparison groups, and 1 had a prospective follow-up in a subset of subjects. There were 6 prospective naturalistic studies and 2 randomized controlled trials. Conclusions: C-ECT and M-ECT are valuable treatment modalities to prevent relapse and recurrence of mood disorders in patients who have responded to an index course of ECT. C-ECT and M-ECT are underused and insufficiently studied despite positive clinical experience of more than 70 years. Studies which are currently under way should allow more definitive recommendations regarding the choice, frequency and duration of C-ECT and M-ECT following acute ECT. Copyright (C) 2011 S. Karger AG, Basel C1 [Petrides, Georgios] N Shore LIJ Hlth Syst, Div Res, Zucker Hillside Hosp, Glen Oaks, NY 11004 USA. [Tobias, Kristen G.; Kellner, Charles H.] Mt Sinai Sch Med, New York, NY USA. [Rudorfer, Matthew V.] NIMH, Bethesda, MD 20892 USA. RP Petrides, G (reprint author), N Shore LIJ Hlth Syst, Div Res, Zucker Hillside Hosp, 7559 263rd St, Glen Oaks, NY 11004 USA. EM petrides@lij.edu OI Kellner, Charles/0000-0001-9663-3571 NR 76 TC 30 Z9 31 U1 3 U2 12 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 0302-282X EI 1423-0224 J9 NEUROPSYCHOBIOLOGY JI Neuropsychobiology PY 2011 VL 64 IS 3 BP 129 EP 140 DI 10.1159/000328943 PG 12 WC Neurosciences; Psychiatry; Psychology SC Neurosciences & Neurology; Psychiatry; Psychology GA 815UM UT WOS:000294555300002 PM 21811083 ER PT J AU Djamshidian, A O'Sullivan, SS Doherty, K Lees, AJ Averbeck, BB AF Djamshidian, Atbin O'Sullivan, Sean S. Doherty, Karen Lees, Andrew J. Averbeck, Bruno B. TI Altruistic punishment in patients with Parkinson's disease with and without impulsive behaviour SO NEUROPSYCHOLOGIA LA English DT Article DE Parkinson's disease; Altruistic punishment; Impulsive compulsive behaviour; Dopaminergic medication ID DOPAMINE DYSREGULATION SYNDROME; CONTROL DISORDERS; COMPULSIVE USE; NEURAL BASIS; REWARD; PERSONALITY; ASSOCIATION; PREVALENCE; MEDICATION; MECHANISMS AB Punishing violators of social norms when there is personal cost is known as altruistic punishment. We tested patients with Parkinson's disease (PD) with and without impulsive-compulsive behaviours (ICBs) and matched control subjects, on and off their regular dopamine replacement therapy on a task, in which the patients decided whether or not to invest a sum of money with a trustee. The sum was then quadrupled and the trustee could decide whether or not to return a portion of the investment. Participants could punish the trustee after they were informed of the trustee's decision. We found that PD patients without ICBs on or off medication punished more often than controls, whereas PD patients with ICBs punished more than controls on medication, but similar to controls off medication. These results suggest a role for dopamine in altruistic punishment decisions in PD patients with impulsive compulsive behaviour. Published by Elsevier Ltd. C1 [Averbeck, Bruno B.] NIMH, Neuropsychol Lab, NIH, Bethesda, MD 20892 USA. [Averbeck, Bruno B.] UCL, Inst Neurol, Sobell Dept Motor Neurosci & Movement Disorders, London WC1N 3BG, England. [Djamshidian, Atbin; O'Sullivan, Sean S.; Doherty, Karen; Lees, Andrew J.] Univ London, Dept Mol Neurosci, London, England. [Djamshidian, Atbin; O'Sullivan, Sean S.; Doherty, Karen; Lees, Andrew J.] Univ London, Reta Lila Weston Inst Neurol Studies, London, England. RP Averbeck, BB (reprint author), NIMH, Neuropsychol Lab, NIH, Bldg 49 Room 1B80,49 Convent Dr,MSC 4415, Bethesda, MD 20892 USA. EM bruno.averbeck@nih.gov RI O'Sullivan, Sean/C-9333-2012; Lees, Andrew/A-6605-2009; OI O'Sullivan, Sean/0000-0002-0583-7956; Djamshidian, Atbin/0000-0001-7174-6000 FU PSP Association; Weston Trust-The Reta Lila Howard Foundation; Wellcome; National Institute of Mental Health; Department of Health's NIHR Biomedical Research Centres FX All authors reported no conflict of interest in the content of this paper. AJL receives honoraria from Novartis, Teva, Meda, Boehringer Ingelheim, GSK, Ipsen, Lundbeck, Allergan, Orion, grants from the PSP Association, Weston Trust-The Reta Lila Howard Foundation and consultancies from Genus. SOS has received honoraria from Britannia Pharmaceuticals. BBA receives research support from Wellcome, and the Intramural research program of the National Institute of Mental Health.; We are grateful to Prof. Peter Brown for critically reading our manuscript and to Dr. Constantinos Kallis for his statistical advice. We like to thank all patients and their partners who participated on this study. This work was undertaken at UCLH/UCL who received a proportion of funding from the Department of Health's NIHR Biomedical Research Centres funding scheme. NR 37 TC 8 Z9 8 U1 1 U2 8 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0028-3932 J9 NEUROPSYCHOLOGIA JI Neuropsychologia PD JAN PY 2011 VL 49 IS 1 BP 103 EP 107 DI 10.1016/j.neuropsychologia.2010.10.012 PG 5 WC Behavioral Sciences; Neurosciences; Psychology, Experimental SC Behavioral Sciences; Neurosciences & Neurology; Psychology GA 712WS UT WOS:000286697600011 PM 20965203 ER PT J AU Tanaka, S Sandrini, M Cohen, LG AF Tanaka, Satoshi Sandrini, Marco Cohen, Leonardo G. TI Modulation of motor learning and memory formation by non-invasive cortical stimulation of the primary motor cortex SO NEUROPSYCHOLOGICAL REHABILITATION LA English DT Article DE Motor learning; Memory; Adaptation; TMS; tDCS; Rehabilitation; Stroke ID TRANSCRANIAL MAGNETIC STIMULATION; USE-DEPENDENT PLASTICITY; INDUCED MOVEMENT THERAPY; CHRONIC STROKE PATIENTS; PARADOXICAL FUNCTIONAL FACILITATION; ALTERNATING-CURRENT STIMULATION; CONSTRAINT-INDUCED THERAPY; PLACEBO-CONTROLLED TRIAL; UPPER EXTREMITY FUNCTION; THETA-BURST STIMULATION AB Transcranial magnetic (TMS) and direct current (tDCS) stimulation are non-invasive brain stimulation techniques that allow researchers to purposefully modulate cortical excitability in focal areas of the brain. Recent work has provided preclinical evidence indicating that TMS and tDCS can facilitate motor performance, motor memory formation, and motor skill learning in healthy subjects and possibly in patients with brain lesions. Although the optimal stimulation parameters to accomplish these goals remain to be determined, and controlled multicentre clinical studies are lacking, these findings suggest that cortical stimulation techniques could become in the future adjuvant strategies in the rehabilitation of motor deficits. The aim of this article is to critically review these findings and to discuss future directions regarding the possibility of combining these techniques with other interventions in neurorehabilitation. C1 [Sandrini, Marco; Cohen, Leonardo G.] NINDS, Human Cort Physiol & Stroke Neurorehabil Sect, NIH, Bethesda, MD 20892 USA. [Tanaka, Satoshi] Natl Inst Physiol Sci, Div Cerebral Integrat, Okazaki, Aichi 444, Japan. [Sandrini, Marco] Uniformed Serv Univ Hlth Sci, Ctr Neurosci & Regenerat Med, Bethesda, MD 20814 USA. RP Cohen, LG (reprint author), NINDS, Human Cort Physiol & Stroke Neurorehabil Sect, NIH, 10 Ctr Dr Bethesda, Bethesda, MD 20892 USA. EM cohenl@ninds.nih.gov RI Sandrini, Marco/J-2276-2014 OI Sandrini, Marco/0000-0002-1664-5722 FU NINDS, NIH; KAKENHI [22700442]; Department of Defense in the Center for Neuroscience and Regenerative Medicine FX This work was supported by the Intramural Research Program of the NINDS, NIH and grants from the Grants-in-Aid for Scientific Research (KAKENHI) to ST (22700442) and by funding from Department of Defense in the Center for Neuroscience and Regenerative Medicine to MS. Satoshi Tanaka and Marco Sandrini contributed equally to this work. NR 198 TC 23 Z9 23 U1 4 U2 24 PU PSYCHOLOGY PRESS PI HOVE PA 27 CHURCH RD, HOVE BN3 2FA, EAST SUSSEX, ENGLAND SN 0960-2011 J9 NEUROPSYCHOL REHABIL JI Neuropsychol. Rehabil. PY 2011 VL 21 IS 5 SI SI BP 650 EP 675 DI 10.1080/09602011.2011.605589 PG 26 WC Neurosciences; Psychology SC Neurosciences & Neurology; Psychology GA 885OS UT WOS:000299789100006 PM 21942897 ER PT J AU Hohman, TJ Beason-Held, LL Lamar, M Resnick, SM AF Hohman, Timothy J. Beason-Held, Lori L. Lamar, Melissa Resnick, Susan M. TI Subjective Cognitive Complaints and Longitudinal Changes in Memory and Brain Function SO NEUROPSYCHOLOGY LA English DT Article DE aging; cerebral blood flow; memory; cognitive failures ID ALZHEIMERS-DISEASE; OLDER-PEOPLE; TEST-PERFORMANCE; VERBAL MEMORY; SELF-REPORT; IMPAIRMENT; DEMENTIA; DECLINE; AGE; ADULTS AB Objective: Subjective cognitive complaints are often used in the diagnosis of memory and other cognitive impairment. This study examined whether cognitive complaints are associated with longitudinal changes in cognition and cross-sectional differences in regional brain function during memory performance in 98 participants with a mean age of 75. Method: The Cognitive Failures Questionnaire (CFQ) assessed cognitive complaints and mixed effects regression models were used to determine whether mean CFQ scores predicted rates of change in cognitive function over a period of 11.5 years. Results: Higher CFQ scores, reflecting increased subjective complaints, were associated with steeper rates of decline in immediate and delayed recall on the California Verbal Learning Test. Voxel-based regression analysis was used to determine the cross-sectional relationship between CFQ scores and regional cerebral blood flow measured by PET during a resting condition and during verbal and figural memory tasks. Higher levels of cognitive complaints were associated with increased activity in insular, lingual and cerebellar areas during memory tasks. Conclusions: These findings offer some support for the validity of subjective cognitive complaints as markers of age related changes in memory and brain activity. C1 [Hohman, Timothy J.] NIA, LPC, Biomed Res Ctr, Baltimore, MD 21224 USA. [Hohman, Timothy J.] American Univ, Dept Psychol, Washington, DC 20016 USA. [Lamar, Melissa] Univ Illinois, Dept Psychiat, Chicago, IL 60612 USA. RP Hohman, TJ (reprint author), NIA, LPC, Biomed Res Ctr, 251 Bayview Blvd,Suite 100, Baltimore, MD 21224 USA. EM hohmantj@mail.nih.gov OI Hohman, Timothy/0000-0002-3377-7014 FU NIH, National Institute on Aging FX This research was supported in part by the Intramural Research Program of the NIH, National Institute on Aging. We are grateful to the BLSA participants and neuroimaging staff for their dedication to these studies and the staff of the Johns Hopkins PET facility for their assistance. NR 39 TC 48 Z9 49 U1 2 U2 13 PU AMER PSYCHOLOGICAL ASSOC PI WASHINGTON PA 750 FIRST ST NE, WASHINGTON, DC 20002-4242 USA SN 0894-4105 J9 NEUROPSYCHOLOGY JI Neuropsychology PD JAN PY 2011 VL 25 IS 1 BP 125 EP 130 DI 10.1037/a0020859 PG 6 WC Psychology, Clinical; Neurosciences; Psychology SC Psychology; Neurosciences & Neurology GA 711AQ UT WOS:000286558500013 PM 20919769 ER PT J AU Swanson, J Baler, RD Volkow, ND AF Swanson, James Baler, Ruben D. Volkow, Nora D. TI Understanding the Effects of Stimulant Medications on Cognition in Individuals with Attention-Deficit Hyperactivity Disorder: A Decade of Progress SO NEUROPSYCHOPHARMACOLOGY LA English DT Review DE methylphenidate; amphetamine; dopamine; prefrontal cortex; executive function; cognitive enhancement ID FUNCTIONAL MAGNETIC-RESONANCE; STRIATAL DOPAMINE TRANSPORTERS; PERFORMANCE-TEST PERFORMANCE; MEDIAL PREFRONTAL CORTEX; BOLD SIGNAL FLUCTUATIONS; SPATIAL WORKING-MEMORY; PARENT-CHILD DYADS; LONG-TERM OUTCOMES; EVENT-RELATED FMRI; DRUG-NAIVE BOYS AB The use of stimulant drugs for the treatment of children with attention-deficit hyperactivity disorder (ADHD) is one of the most widespread pharmacological interventions in child psychiatry and behavioral pediatrics. This treatment is well grounded on controlled studies showing efficacy of low oral doses of methylphenidate and amphetamine in reducing the behavioral symptoms of the disorder as reported by parents and teachers, both for the cognitive (inattention and impulsivity) and noncognitive (hyperactivity) domains. Our main aim is to review the objectively measured cognitive effects that accompany the subjectively assessed clinical responses to stimulant medications. Recently, methods from the cognitive neurosciences have been used to provide information about brain processes that underlie the cognitive deficits of ADHD and the cognitive effects of stimulant medications. We will review some key findings from the recent literature, and then offer interpretations of the progress that has been made over the past decade in understanding the cognitive effects of stimulant medication on individuals with ADHD. Neuropsychopharmacology Reviews (2011) 36, 207-226; doi: 10.1038/npp.2010.160; published online 29 September 2010 C1 [Baler, Ruben D.; Volkow, Nora D.] NIDA, NIH, Bethesda, MD 20892 USA. [Swanson, James] Univ Calif Irvine, Dept Pediat, Irvine, CA 92717 USA. RP Volkow, ND (reprint author), NIDA, NIH, Bethesda, MD 20892 USA. EM nvolkow@nida.nih.gov NR 189 TC 101 Z9 103 U1 12 U2 65 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0893-133X J9 NEUROPSYCHOPHARMACOL JI Neuropsychopharmacology PD JAN PY 2011 VL 36 IS 1 BP 207 EP 226 DI 10.1038/npp.2010.160 PG 20 WC Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA 688TR UT WOS:000284877300011 PM 20881946 ER PT J AU Goldstein, RZ Volkow, ND AF Goldstein, Rita Z. Volkow, Nora D. TI Oral Methylphenidate Normalizes Cingulate Activity and Decreases Impulsivity in Cocaine Addiction During an Emotionally Salient Cognitive Task SO NEUROPSYCHOPHARMACOLOGY LA English DT Editorial Material ID ANTERIOR CINGULATE; CORTEX C1 [Goldstein, Rita Z.] Brookhaven Natl Lab, Ctr Translat Neuroimaging, Dept Med Res, Upton, NY 11973 USA. [Volkow, Nora D.] NIAAA, Rockville, MD 20852 USA. [Volkow, Nora D.] Natl Inst Drug Abuse, Bethesda, MD USA. RP Goldstein, RZ (reprint author), Brookhaven Natl Lab, Ctr Translat Neuroimaging, Dept Med Res, Upton, NY 11973 USA. EM rgoldstein@bnl.gov FU NCRR NIH HHS [5-M01-RR-10710, M01 RR010710]; NIDA NIH HHS [R01DA023579, R01 DA023579] NR 6 TC 15 Z9 15 U1 0 U2 1 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0893-133X J9 NEUROPSYCHOPHARMACOL JI Neuropsychopharmacology PD JAN PY 2011 VL 36 IS 1 BP 366 EP 367 DI 10.1038/npp.2010.145 PG 3 WC Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA 688TR UT WOS:000284877300030 PM 21116260 ER PT J AU Nair, SG Navarre, BM Cifani, C Pickens, CL Bossert, JM Shaham, Y AF Nair, Sunila G. Navarre, Brittany M. Cifani, Carlo Pickens, Charles L. Bossert, Jennifer M. Shaham, Yavin TI Role of Dorsal Medial Prefrontal Cortex Dopamine D1-Family Receptors in Relapse to High-Fat Food Seeking Induced by the Anxiogenic Drug Yohimbine SO NEUROPSYCHOPHARMACOLOGY LA English DT Article DE diet; medial prefrontal cortex; reinstatement; relapse; stress; yohimbine ID CORTICOTROPIN-RELEASING-FACTOR; CUE-INDUCED REINSTATEMENT; COCAINE-INDUCED REINSTATEMENT; CONDITIONED PLACE PREFERENCE; NUCLEUS-ACCUMBENS CORE; EXCESSIVE SUGAR INTAKE; STRESS-INDUCED RELAPSE; C-FOS; 5-HT2C RECEPTORS; HEROIN-SEEKING AB In humans, relapse to maladaptive eating habits during dieting is often provoked by stress. In rats, the anxiogenic drug yohimbine, which causes stress-like responses in both humans and nonhumans, reinstates food seeking in a relapse model. In this study, we examined the role of medial prefrontal cortex (mPFC) dopamine D1-family receptors, previously implicated in stress-induced reinstatement of drug seeking, in yohimbine-induced reinstatement of food seeking. We trained food-restricted rats to lever press for 35% high-fat pellets every other day (9-15 sessions, 3 h each); pellet delivery was accompanied by a discrete tone-light cue. We then extinguished operant responding for 10-16 days by removing the pellets. Subsequently, we examined the effect of yohimbine (2 mg/kg, i.p.) on reinstatement of food seeking and Fos (a neuronal activity marker) induction in mPFC. We then examined the effect of systemic injections of the D1-family receptor antagonist SCH23390 (10 mu g/kg, s.c.) on yohimbine-induced reinstatement and Fos induction, and that of mPFC SCH23390 (0.5 and 1.0 mu g/side) injections on this reinstatement. Yohimbine-induced reinstatement was associated with strong Fos induction in the dorsal mPFC and with weaker Fos induction in the ventral mPFC. Systemic SCH23390 injections blocked both yohimbine-induced reinstatement and mPFC Fos induction. Dorsal, but not ventral, mPFC injections of SCH23390 decreased yohimbine-induced reinstatement of food seeking. In addition, dorsal mPFC SCH23390 injections decreased pellet-priming-induced reinstatement, but had no effect on ongoing high-fat pellet self-administration or discrete-cue-induced reinstatement. Results indicate a critical role of dorsal mPFC dopamine D1-family receptors in stress-induced relapse to palatable food seeking, as well as relapse induced by acute re-exposure to food taste, texture, and smell. Neuropsychopharmacology (2011) 36, 497-510; doi:10.1038/npp.2010.181; published online 20 October 2010 C1 [Nair, Sunila G.; Navarre, Brittany M.; Cifani, Carlo; Pickens, Charles L.; Bossert, Jennifer M.; Shaham, Yavin] NIDA, Behav Neurosci Branch, IRP, NIH,DHHS, Baltimore, MD 21224 USA. RP Shaham, Y (reprint author), NIDA, Behav Neurosci Branch, IRP, NIH,DHHS, 251 Bayview Blvd,Suite 200, Baltimore, MD 21224 USA. EM Yshaham@intra.nida.nih.gov RI shaham, yavin/G-1306-2014; OI Cifani, Carlo/0000-0001-6180-828X FU National Institute on Drug Abuse FX The work was supported by the Intramural Research Program of the National Institute on Drug Abuse. We thank Drs Bruce Hope and Eisuke Koya for their help with the immunohistochemical assays and image analyses, and Dr Kenner Rice for synthesizing M100907 for experiment 4. NR 109 TC 45 Z9 46 U1 0 U2 5 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0893-133X J9 NEUROPSYCHOPHARMACOL JI Neuropsychopharmacology PD JAN PY 2011 VL 36 IS 2 BP 497 EP 510 DI 10.1038/npp.2010.181 PG 14 WC Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA 694JE UT WOS:000285292200011 PM 20962767 ER PT J AU Sandrini, M Umilta, C Rusconi, E AF Sandrini, Marco Umilta, Carlo Rusconi, Elena TI The use of transcranial magnetic stimulation in cognitive neuroscience: A new synthesis of methodological issues SO NEUROSCIENCE AND BIOBEHAVIORAL REVIEWS LA English DT Review DE TMS; rTMS; Theta burst; State-dependency; fMRI; EEG; Safety; Number processing ID HUMAN MOTOR CORTEX; POSTERIOR PARIETAL CORTEX; CONCURRENT TMS-FMRI; MENTAL NUMBER LINE; DORSOLATERAL PREFRONTAL CORTEX; VENTRAL PREMOTOR CORTEX; PARADOXICAL FUNCTIONAL FACILITATION; VISUAL CORTICAL EXCITABILITY; THETA-BURST STIMULATION; ANTERIOR TEMPORAL-LOBES AB Transcranial magnetic stimulation (TMS) has become a mainstay of cognitive neuroscience, thus facing new challenges due to its widespread application on behaviorally silent areas. In this review we will summarize the main technical and methodological considerations that are necessary when using TMS in cognitive neuroscience, based on a corpus of studies and technical improvements that has become available in most recent years. Although TMS has been applied only relatively recently on a large scale to the study of higher functions, a range of protocols that elucidate how this technique can be used to investigate a variety of issues is already available, such as single pulse, paired pulse, dual-site, repetitive and theta burst TMS. Finally, we will touch on recent promising approaches that provide powerful new insights about causal interactions among brain regions (i.e., TMS with other neuroimaging techniques) and will enable researchers to enhance the functional resolution of TMS (i.e., state-dependent TMS). We will end by briefly summarizing and discussing the implications of the newest safety guidelines. (C) 2010 Elsevier Ltd. All rights reserved. C1 [Sandrini, Marco] NINDS, Human Cort Physiol & Stroke Neurorehabil Sect, NIH, Bethesda, MD 20892 USA. [Sandrini, Marco] Uniformed Serv Univ Hlth Sci, Ctr Neurosci & Regenerat Med, Henry M Jackson Fdn, Rockville, MD 20852 USA. [Umilta, Carlo] Univ Padua, Dept Gen Psychol, I-35131 Padua, Italy. [Rusconi, Elena] UCL, Dept Secur & Crime Sci, London WC1E 7HN, England. [Rusconi, Elena] Univ Trent, Ctr Mind Brain Sci CIMeC, Funct Neuroimaging Labs, I-38060 Mattarello, TN, Italy. RP Sandrini, M (reprint author), NINDS, Human Cort Physiol & Stroke Neurorehabil Sect, NIH, 10 Ctr Dr, Bethesda, MD 20892 USA. EM marco.sandrini@nih.gov RI Sandrini, Marco/J-2276-2014 OI Sandrini, Marco/0000-0002-1664-5722 NR 252 TC 93 Z9 93 U1 8 U2 63 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0149-7634 J9 NEUROSCI BIOBEHAV R JI Neurosci. Biobehav. Rev. PD JAN PY 2011 VL 35 IS 3 BP 516 EP 536 DI 10.1016/j.neubiorev.2010.06.005 PG 21 WC Behavioral Sciences; Neurosciences SC Behavioral Sciences; Neurosciences & Neurology GA 712CJ UT WOS:000286639900013 PM 20599555 ER PT J AU Crawley, JN AF Crawley, Jacqueline N. TI Behavioral phenotyping strategies for genetic mouse models of autism SO NEUROSCIENCE RESEARCH LA English DT Meeting Abstract C1 [Crawley, Jacqueline N.] NIMH, LBN, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0168-0102 J9 NEUROSCI RES JI Neurosci. Res. PY 2011 VL 71 SU S BP E38 EP E38 DI 10.1016/j.neures.2011.07.167 PG 1 WC Neurosciences SC Neurosciences & Neurology GA 998DT UT WOS:000308218100164 ER PT J AU Hayashi, T AF Hayashi, Teruo TI The molecular function of the novel chaperone sigma-1 receptor SO NEUROSCIENCE RESEARCH LA English DT Meeting Abstract C1 [Hayashi, Teruo] NIDA, Cellular Stress Signaling Unit, Cellular Pathobiol Sect, IRP,NIH, Baltimore, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0168-0102 J9 NEUROSCI RES JI Neurosci. Res. PY 2011 VL 71 SU S BP E34 EP E34 DI 10.1016/j.neures.2011.07.146 PG 1 WC Neurosciences SC Neurosciences & Neurology GA 998DT UT WOS:000308218100143 ER PT J AU Mishra, S Hoon, M AF Mishra, Santosh Hoon, Mark TI TRPV1 lineage neurons and their functional role in thermal nociception SO NEUROSCIENCE RESEARCH LA English DT Meeting Abstract C1 [Mishra, Santosh; Hoon, Mark] Natl Inst Dent & Craniofacial Res, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0168-0102 J9 NEUROSCI RES JI Neurosci. Res. PY 2011 VL 71 SU S BP E80 EP E80 DI 10.1016/j.neures.2011.07.341 PG 1 WC Neurosciences SC Neurosciences & Neurology GA 998DT UT WOS:000308218100339 ER PT J AU Shukla, V Pant, HC AF Shukla, Varsha Pant, Harish C. TI Hyperphosphorylation of tau by deregulated Cdk5 (Cdk5/p25) activity is inhibited by its truncated activator (p35) SO NEUROSCIENCE RESEARCH LA English DT Meeting Abstract C1 [Shukla, Varsha; Pant, Harish C.] NINDS, Neurochem Lab, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0168-0102 J9 NEUROSCI RES JI Neurosci. Res. PY 2011 VL 71 SU S BP E186 EP E186 DI 10.1016/j.neures.2011.07.804 PG 1 WC Neurosciences SC Neurosciences & Neurology GA 998DT UT WOS:000308218101049 ER PT J AU Masdeu, JC AF Masdeu, Joseph C. TI Neuroimaging in Psychiatric Disorders SO NEUROTHERAPEUTICS LA English DT Article DE Magnetic resonance imaging; Positron emission tomography; Single photon emission tomography; Depression; Schizophrenia; Drug development ID POSITRON-EMISSION-TOMOGRAPHY; EXTRASTRIATAL DOPAMINE-D-2 RECEPTORS; SEROTONIN TRANSPORTER OCCUPANCY; MAJOR DEPRESSIVE DISORDER; ALZHEIMERS-DISEASE; FRONTOTEMPORAL DEMENTIA; SCHIZOPHRENIC SUBJECTS; PREFRONTAL CORTEX; DRUG DISCOVERY; BASE-LINE AB In psychiatry, neuroimaging facilitates the diagnosis of psychiatric disorders and the development of new medications. It is used to detect structural lesions causing psychosis and to differentiate depression from neurodegenerative disorders or brain tumors. Functional neuroimaging, mostly in the form of molecular neuroimaging with positron emission tomography or single photon emission tomography, facilitates the identification of therapeutic targets, the determination of the dose of a new drug needed to occupy its target in the brain, and the selection of patients for clinical trials. C1 NIMH, Sect Integrat Neuroimaging, Intramural Res Program, NIH,CBDS, Bethesda, MD 20892 USA. RP Masdeu, JC (reprint author), NIMH, Sect Integrat Neuroimaging, Intramural Res Program, NIH,CBDS, 9000 Rockville Pike,Bldg 10,Room 3C111, Bethesda, MD 20892 USA. EM masdeu@nih.gov FU National Institute of Mental Health, National Institutes of Health, USA FX This work was supported by the Intramural Research Program of the National Institute of Mental Health, National Institutes of Health, USA. NR 58 TC 7 Z9 8 U1 2 U2 6 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1933-7213 EI 1878-7479 J9 NEUROTHERAPEUTICS JI Neurotherapeutics PD JAN PY 2011 VL 8 IS 1 BP 93 EP 102 DI 10.1007/s13311-010-0006-0 PG 10 WC Clinical Neurology; Neurosciences; Pharmacology & Pharmacy SC Neurosciences & Neurology; Pharmacology & Pharmacy GA 750RU UT WOS:000289566500011 PM 21274689 ER PT J AU Zhang, W Phillips, K Wielgus, AR Liu, J Albertini, A Zucca, FA Faust, R Qian, SY Miller, DS Chignell, CF Wilson, B Jackson-Lewis, V Przedborski, S Joset, D Loike, J Hong, JS Sulzer, D Zecca, L AF Zhang, Wei Phillips, Kester Wielgus, Albert R. Liu, Jie Albertini, Alberto Zucca, Fabio A. Faust, Rudolph Qian, Steven Y. Miller, David S. Chignell, Colin F. Wilson, Belinda Jackson-Lewis, Vernice Przedborski, Serge Joset, Danielle Loike, John Hong, Jau-Shyong Sulzer, David Zecca, Luigi TI Neuromelanin Activates Microglia and Induces Degeneration of Dopaminergic Neurons: Implications for Progression of Parkinson's Disease SO NEUROTOXICITY RESEARCH LA English DT Article DE Substantia nigra; Neuroinflammation; Microglia; Neurodegenerative diseases ID SUBSTANTIA-NIGRA; ALZHEIMERS-DISEASE; NEUROTOXICITY; MODEL; NEURODEGENERATION; MECHANISMS; FEATURES; BRAIN; IRON AB In Parkinson's disease (PD), there is a progressive loss of neuromelanin (NM)-containing dopamine neurons in substantia nigra (SN) which is associated with microgliosis and presence of extracellular NM. Herein, we have investigated the interplay between microglia and human NM on the degeneration of SN dopaminergic neurons. Although NM particles are phagocytized and degraded by microglia within minutes in vitro, extracellular NM particles induce microglial activation and ensuing production of superoxide, nitric oxide, hydrogen peroxide (H(2)O(2)), and pro-inflammatory factors. Furthermore, NM produces, in a microglia-depended manner, neurodegeneration in primary ventral midbrain cultures. Neurodegeneration was effectively attenuated with microglia derived from mice deficient in macrophage antigen complex-1, a microglial integrin receptor involved in the initiation of phagocytosis. Neuronal loss was also attenuated with microglia derived from mice deficient in phagocytic oxidase, a subunit of NADPH oxidase, that is responsible for superoxide and H(2)O(2) production, or apocynin, an NADPH oxidase inhibitor. In vivo, NM injected into rat SN produces microgliosis and a loss of tyrosine hydroxylase neurons. Thus, these results show that extracellular NM can activate microglia, which in turn may induce dopaminergic neurodegeneration in PD. Our study may have far-reaching implications, both pathogenic and therapeutic. C1 [Albertini, Alberto; Zucca, Fabio A.; Zecca, Luigi] Italian Natl Res Council, Inst Biomed Technol, I-20090 Milan, Italy. [Jackson-Lewis, Vernice] Columbia Univ, Dept Neurol, New York, NY 10032 USA. [Przedborski, Serge] Columbia Univ, Dept Neurol Pathol & Cell Biol, New York, NY 10032 USA. [Joset, Danielle; Loike, John] Columbia Univ, Dept Physiol & Cellular Biophys, New York, NY 10032 USA. [Zhang, Wei] Beijing Tiantan Hosp, Dept Neurol, Beijing 100050, Peoples R China. [Phillips, Kester; Faust, Rudolph; Sulzer, David] Columbia Univ, Dept Psychiat Neurol & Pharmacol, New York, NY 10032 USA. [Wielgus, Albert R.; Qian, Steven Y.; Miller, David S.; Chignell, Colin F.; Wilson, Belinda; Hong, Jau-Shyong] NIEHS, Neuropharmacol Sect, Lab Pharmacol & Chem, NIH, Res Triangle Pk, NC 27709 USA. [Liu, Jie] NIEHS, Inorgan Carcinogenesis Sect, Comparat Carcinogenesis Lab, NCI,NIH, Res Triangle Pk, NC 27709 USA. RP Zecca, L (reprint author), Italian Natl Res Council, Inst Biomed Technol, Via Cervi 93, I-20090 Milan, Italy. EM luigi.zecca@itb.cnr.it RI Zucca, Fabio/O-4368-2015; OI Zucca, Fabio/0000-0003-1230-1129; albertini, alberto/0000-0002-7989-649X FU Michael J. Fox Foundation (New York, NY, USA); MIUR-FIRB (Italy) [RBNE03PX83_002]; National Parkinson Foundation-Parkinson Disease's Foundation (Miami, FL; and New York, NY, USA); NINDS [NS062180, NS11766-27A1, NS38370-09]; NIA [AG21617-01A1]; US DoD [DAMD 17-03-1-02]; Parkinson's Disease Foundation (NY, USA); MDA/WOW; Hartman Foundation; NIH/NIEHS FX The authors thank the Legal Medicine Section, Department of Human Morphology and Biomedical Sciences, University of Milano, and the authors also thank Ms. Chiara Bellei for skilful assistance. K.P., A.A., F.A.Z., R.F., D.S., and L.Z. were supported with the grant of Michael J. Fox Foundation (New York, NY, USA), MIUR-FIRB Project RBNE03PX83_002 on Protein Folding and Aggregation: Metal and Biomolecules in Protein Conformational Diseases (Italy) and Joint Research Grant of National Parkinson Foundation-Parkinson Disease's Foundation (Miami, FL; and New York, NY, USA). S.P. is supported by the NINDS Grants NS062180, NS11766-27A1, and NS38370-09, the NIA Grant AG21617-01A1, the US DoD Contract DAMD 17-03-1-02, as well as the Parkinson's Disease Foundation (NY, USA), the MDA/WOW, and the Hartman Foundation. This research was supported in part by the Intramural Research Program of the NIH/NIEHS. NR 31 TC 69 Z9 73 U1 1 U2 22 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1029-8428 J9 NEUROTOX RES JI Neurotox. Res. PD JAN PY 2011 VL 19 IS 1 BP 63 EP 72 DI 10.1007/s12640-009-9140-z PG 10 WC Neurosciences SC Neurosciences & Neurology GA 721QB UT WOS:000287368600007 PM 19957214 ER PT J AU Eugenin, EA King, JE Hazleton, JE Major, EO Bennett, MVL Zukin, RS Berman, JW AF Eugenin, E. A. King, J. E. Hazleton, J. E. Major, E. O. Bennett, M. V. L. Zukin, R. S. Berman, Joan W. TI Differences in NMDA Receptor Expression During Human Development Determine the Response of Neurons to HIV-Tat-mediated Neurotoxicity SO NEUROTOXICITY RESEARCH LA English DT Article DE HIV-1; NeuroAIDS; Glutamate; NMDA; Dementia; HAND ID IMMUNODEFICIENCY-VIRUS TYPE-1; HUMAN-FETAL BRAIN; CENTRAL-NERVOUS-SYSTEM; AMINO-ACID RECEPTORS; D-ASPARTATE RECEPTOR; NF-KAPPA-B; NEUROLOGICAL DISEASE; PROGENITOR CELLS; PROTEINS TAT; JC VIRUS AB HIV infection of the CNS can result in neurologic dysfunction in a significant number of infected individuals. NeuroAIDS is characterized by neuronal injury and loss, yet there is no evidence of HIV infection in neurons. Thus, neuronal damage and dropout are likely due to indirect effects of HIV infection of other CNS cells, through elaboration of inflammatory factors and neurotoxic viral proteins, including the viral transactivating protein tat. We and others demonstrated that tat induces apoptosis in differentiated mature human neurons. We now demonstrate that the high level of tat toxicity observed in human neurons involves specific developmental stages that correlate with N-Methyl-D-Aspartate receptor (NMDAR) expression, and that tat toxicity is also dependent upon the species being analyzed. Our results indicate that tat treatment of primary cultures of differentiated human neurons with significant amounts of NMDAR expression induces extensive apoptosis. In contrast, tat treatment induces only low levels of apoptosis in primary cultures of immature human neurons with low or minimal expression of NMDAR. In addition, tat treatment has minimal effect on rat hippocampal neurons in culture, despite their high expression of NMDAR. We propose that this difference may be due to low expression of the NR2A subunit. These findings are important for an understanding of the many differences among tissue culture systems and species used to study HIV-tat-mediated toxicity. C1 [Eugenin, E. A.; King, J. E.; Hazleton, J. E.; Berman, Joan W.] Albert Einstein Coll Med, Dept Pathol, Bronx, NY 10461 USA. [Berman, Joan W.] Albert Einstein Coll Med, Dept Microbiol Immunol, Bronx, NY 10461 USA. [Bennett, M. V. L.; Zukin, R. S.] Albert Einstein Coll Med, Dept Neurosci, Bronx, NY 10461 USA. [Major, E. O.] NINDS, NIH, Mol Med & Virol Sect, Bethesda, MD 20892 USA. RP Berman, JW (reprint author), Albert Einstein Coll Med, Dept Pathol, Forchheimer 727,1300 Morris Pk Ave, Bronx, NY 10461 USA. EM joan.berman@einstein.yu.edu FU National Institutes of Mental Health [MH070297, MH075679, MH083497, MH076679]; National Institute of Neurological Disorders and Stroke [NS055363, NS045287, NS020752]; MSTP [5 T32 GM007288]; HIV AIDS and Opportunistic Infection Institutional Training Grant [T32 AI-007501]; NIH Centers for AIDS Research at the Albert Einstein College of Medicine [(CFAR) AI-051519] FX We are grateful to Dr. Brad Poulos and The Human Fetal Tissue Repository at the AECOM. This work was supported by the National Institutes of Mental Health Grants MH070297, MH075679, and MH083497 to J. W. B. and by a RO1 grant from the National Institute of Mental Health (MH076679) to E.A.E., National Institute of Neurological Disorders and Stroke (NS055363 and NS045287 to M.V.L.B. and NS020752 to R.S.Z.), MSTP Training Grant, 5 T32 GM007288 (to JEK and JEH), and from the HIV AIDS and Opportunistic Infection Institutional Training Grant, T32 AI-007501 (to JEH). We thank the NIH Centers for AIDS Research Grant (CFAR) AI-051519 at the Albert Einstein College of Medicine. NR 48 TC 13 Z9 13 U1 0 U2 4 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1029-8428 J9 NEUROTOX RES JI Neurotox. Res. PD JAN PY 2011 VL 19 IS 1 BP 138 EP 148 DI 10.1007/s12640-010-9150-x PG 11 WC Neurosciences SC Neurosciences & Neurology GA 721QB UT WOS:000287368600015 PM 20094923 ER PT J AU Khalsa, JH AF Khalsa, Jag H. TI Preface to understanding developmental consequences of prenatal drug exposure: Biological and environmental effects and their interactions SO NEUROTOXICOLOGY AND TERATOLOGY LA English DT Editorial Material DE Drug abuse; Pregnancy C1 Natl Inst Drug Abuse, Med Consequences Branch, Div Pharmacotherapies & Med Consequences Drug Abu, NIH, Bethesda, MD 20892 USA. RP Khalsa, JH (reprint author), Natl Inst Drug Abuse, Med Consequences Branch, Div Pharmacotherapies & Med Consequences Drug Abu, NIH, 6001 Execut Blvd,Room 4137,MSC 9551, Bethesda, MD 20892 USA. EM jkhalsa@nida.nih.gov FU Intramural NIH HHS [Z99 DA999999] NR 8 TC 0 Z9 0 U1 1 U2 2 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0892-0362 J9 NEUROTOXICOL TERATOL JI Neurotoxicol. Teratol. PD JAN-FEB PY 2011 VL 33 IS 1 SI SI BP 3 EP 4 DI 10.1016/j.ntt.2010.10.009 PG 2 WC Neurosciences; Toxicology SC Neurosciences & Neurology; Toxicology GA 724XN UT WOS:000287609800001 PM 21056101 ER PT J AU Bada, HS Bann, CM Bauer, CR Shankaran, S Lester, B LaGasse, L Hammond, J Whitaker, T Das, A Tan, S Higgins, R AF Bada, Henrietta S. Bann, Carla M. Bauer, Charles R. Shankaran, Seetha Lester, Barry LaGasse, Linda Hammond, Jane Whitaker, Toni Das, Abhik Tan, Sylvia Higgins, Rosemary TI Preadolescent behavior problems after prenatal cocaine exposure: Relationship between teacher and caretaker ratings (Maternal Lifestyle Study) SO NEUROTOXICOLOGY AND TERATOLOGY LA English DT Article DE Prenatal cocaine; Externalizing behavior; Attention problems; Prenatal opiate; Caretaker depression; Community violence; School behavior ID SCHOOL-AGE-CHILDREN; IN-UTERO; COMMUNITY VIOLENCE; DRUG EXPOSURE; INFANTS; OUTCOMES; MOTHERS; MODEL; BRAIN; RISK AB Background: We previously reported an association between prenatal cocaine exposure (PCE) and childhood behavior problems as observed by the parent or caretaker. However, these behavior problems may not manifest in a structured environment, such as a school setting. Objective: We determined whether there is an association between PCE and school behavior problems and whether ratings of behavior problems from the teacher differ from those noted by the parent or caretaker. Methods: The Maternal Lifestyle Study, a multicenter study, enrolled 1388 children with and without PCE at one month of age for longitudinal assessment Teachers masked to prenatal drug exposure status completed the Teacher Report Form (TRF/6-18) when children were 7, 9, and 11 years old. We also administered the Child Behavior Checklist-parent report (CBCL) to the parent/caretaker at same ages and then at 13 years. We performed latent growth curve modeling to determine whether high PCE will predict externalizing, internalizing, total behavior, and attention problems at 7 years of age and whether changes in problems' scores over time differ between those exposed and non-exposed from both teacher and parent report. Besides levels of PCE as predictors, we controlled for the following covariates, namely: site, child characteristics (gender and other prenatal drug exposures), family level influences (maternal age, depression and psychological symptomatology, continuing drug use, exposure to domestic violence, home environment and socioeconomic status), and community level factors (neighborhood and community violence). Results: The mean behavior problem T scores from the teacher report were significantly higher than ratings by the parent or caretaker. Latent growth curve modeling revealed a significant relationship between intercepts of problem T scores from teacher and parent ratings; i.e., children that were rated poorly by teachers were also rated poorly by their parent/caretaker or vice versa. After controlling for covariates, we found high PCE to be a significant predictor of higher externalizing behavior problem T scores from both parent and teacher report at 7 years (p = 0.034 and p = 0.021, respectively) in comparison to non-PCE children. These differences in scores from either teacher or caregiver were stable through subsequent years or did not change significantly over time. Boys had higher T scores than girls on internalizing and total problems by caretaker report; they also had significantly higher T scores for internalizing, total, and attention problems by teacher ratings; the difference was marginally significant for externalizing behavior (p = 0.070). Caretaker postnatal use of tobacco, depression, and community violence were significant predictors of all behavior problems rated by parent/caretaker, while lower scores on the home environment predicted all behavior outcomes by the teacher report. Conclusions: Children with high PCE are likely to manifest externalizing behavior problems; their behavior problem scores at 7 years from either report of teacher or parent remained higher than scores of non-exposed children on subsequent years. Screening and identification of behavior problems at earlier ages could make possible initiation of intervention, while considering the likely effects of other confounders. (C) 2010 Elsevier Inc. All rights reserved. C1 [Bada, Henrietta S.] Univ Kentucky, Albert B Chandler Med Ctr, Dept Pediat, Lexington, KY 40536 USA. [Bann, Carla M.; Hammond, Jane; Das, Abhik; Tan, Sylvia] RTI Int, Res Triangle Pk, NC 27709 USA. [Bauer, Charles R.] Univ Miami, Sch Med, Dept Pediat, Miami, FL 33136 USA. [Shankaran, Seetha] Wayne State Univ, Sch Med, Dept Pediat, Detroit, MI 48201 USA. [Lester, Barry; LaGasse, Linda] Brown Univ, Sch Med, Dept Pediat, Providence, RI 02905 USA. [Whitaker, Toni] Univ Tennessee HSC, Dept Pediat, Memphis, TN 38163 USA. [Higgins, Rosemary] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Rockville, MD 20847 USA. RP Bada, HS (reprint author), Univ Kentucky, Albert B Chandler Med Ctr, Dept Pediat, 800 Rose St,Room MS 477, Lexington, KY 40536 USA. EM hbada2@uky.edu FU National Institutes of Health; Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD); National Institute on Drug Abuse (NIDA); Administration on Children, Youth, and Families; Center for Substance Abuse and Treatment; NICHD FX The National Institutes of Health, the Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD), the National Institute on Drug Abuse (NIDA), the Administration on Children, Youth, and Families, and the Center for Substance Abuse and Treatment provided grant support for recruiting subjects into the Maternal Lifestyle Study in 1993-1995. NIDA and NICHD provided funding to conduct follow-up examinations in five phases: at 1, 4, 8, 10, 12, 18, 24, and 36 months corrected age (Phase 1 and Phase II); at 31/2, 4, 41/2, 5, 51/2, 6, and 7 years of age (Phase III); and at 8, 9, 10, and 11 years of age (Phase IV). NICHD, NIDA, and NIMH provided continuing funding for ages 12, 13, 14, 15, and 16 years (Phase V). The funding agencies provided overall oversight of study conduct, but all data analyses and interpretation were completed independent of the funding agencies. We are indebted to our medical and nursing colleagues and the infants and their parents who agreed to take part in this study. NR 69 TC 29 Z9 29 U1 1 U2 4 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0892-0362 J9 NEUROTOXICOL TERATOL JI Neurotoxicol. Teratol. PD JAN-FEB PY 2011 VL 33 IS 1 SI SI BP 78 EP 87 DI 10.1016/j.ntt.2010.06.005 PG 10 WC Neurosciences; Toxicology SC Neurosciences & Neurology; Toxicology GA 724XN UT WOS:000287609800010 PM 20600844 ER PT J AU Delaney-Black, V Chiodo, LM Hannigan, JH Greenwald, MK Janisse, J Patterson, G Huestis, MA Partridge, RT Ager, J Sokol, RJ AF Delaney-Black, Virginia Chiodo, Lisa M. Hannigan, John H. Greenwald, Mark K. Janisse, James Patterson, Grace Huestis, Marilyn A. Partridge, Robert T. Ager, Joel Sokol, Robert J. TI Prenatal and postnatal cocaine exposure predict teen cocaine use SO NEUROTOXICOLOGY AND TERATOLOGY LA English DT Article DE Cocaine; Opiates; Marijuana; Self-report; Biologic sample ID SUBSTANCE-USE INITIATION; ATTENTION-DEFICIT/HYPERACTIVITY DISORDER; DRUG-USE; ADULT RATS; BEHAVIOR PROBLEMS; CHILD-BEHAVIOR; RECEPTOR-BINDING; YOUNG ADULTHOOD; MENTAL-HEALTH; CANNABIS USE AB Preclinical studies have identified alterations in cocaine and alcohol self-administration and behavioral responses to pharmacological challenges in adolescent offspring following prenatal exposure. To date, no published human studies have evaluated the relation between prenatal cocaine exposure and postnatal adolescent cocaine use. Human studies of prenatal cocaine-exposed children have also noted an increase in behaviors previously associated with substance use/abuse in teens and young adults, specifically childhood and teen externalizing behaviors, impulsivity, and attention problems. Despite these findings, human research has not addressed prior prenatal exposure as a potential predictor of teen drug use behavior. The purpose of this study was to evaluate the relations between prenatal cocaine exposure and teen cocaine use in a prospective longitudinal cohort (n = 316) that permitted extensive control for child, parent and community risk factors. Logistic regression analyses and Structural Equation Modeling revealed that both prenatal exposure and postnatal parent/caregiver cocaine use were uniquely related to teen use of cocaine at age 14 years. Teen cocaine use was also directly predicted by teen community violence exposure and caregiver negativity, and was indirectly related to teen community drug exposure. These data provide further evidence of the importance of prenatal exposure, family and community factors in the intergenerational transmission of teen/young adult substance abuse/use. (C) 2010 Elsevier Inc. All rights reserved. C1 [Delaney-Black, Virginia; Patterson, Grace] Wayne State Univ, Carman & Ann Adams Dept Pediat, Detroit, MI 48201 USA. [Chiodo, Lisa M.] Wayne State Univ, Coll Nursing, Detroit, MI 48201 USA. [Hannigan, John H.; Sokol, Robert J.] Wayne State Univ, Dept Obstet & Gynecol, Detroit, MI 48201 USA. [Hannigan, John H.; Partridge, Robert T.] Wayne State Univ, Dept Psychol, Detroit, MI 48201 USA. [Hannigan, John H.; Sokol, Robert J.] Wayne State Univ, CS Mott Ctr Human Growth & Dev, Detroit, MI 48201 USA. [Hannigan, John H.] Wayne State Univ, Merrill Palmer Skillman Inst, Detroit, MI 48201 USA. [Greenwald, Mark K.] Wayne State Univ, Dept Psychiat & Behav Neurosci, Detroit, MI 48201 USA. [Janisse, James; Ager, Joel] Wayne State Univ, Dept Family Med & Publ Hlth Sci, Detroit, MI 48201 USA. [Huestis, Marilyn A.] Natl Inst Drug Abuse, Intramural Res Program, Baltimore, MD 21224 USA. RP Delaney-Black, V (reprint author), Childrens Hosp Michigan, Carmen & Ann Adams Dept Pediat, 3901 Beaubien, Detroit, MI 48201 USA. EM vdelaney@med.wayne.edu RI Chiodo, Lisa/G-1427-2015 OI Chiodo, Lisa/0000-0001-7052-3569 FU National Institute of Health [R01-DA08524, R01-DA016373]; National Institute on Drug Abuse FX This study was funded in part by grants from the National Institute of Health (R01-DA08524 and R01-DA016373) to V. Delaney-Black. MA. Huestis was supported by the National Institute on Drug Abuse Intramural Research Program. Preliminary reports of some of these findings were presented to the annual meetings of PAS and ISDP in 2009. NR 102 TC 35 Z9 37 U1 3 U2 17 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0892-0362 J9 NEUROTOXICOL TERATOL JI Neurotoxicol. Teratol. PD JAN-FEB PY 2011 VL 33 IS 1 SI SI BP 110 EP 119 DI 10.1016/j.ntt.2010.06.011 PG 10 WC Neurosciences; Toxicology SC Neurosciences & Neurology; Toxicology GA 724XN UT WOS:000287609800013 PM 20609384 ER PT J AU Wakschlag, LS Henry, DB Blair, RJR Dukic, V Burns, J Pickett, KE AF Wakschlag, Lauren S. Henry, David B. Blair, R. James R. Dukic, Vanja Burns, James Pickett, Kate E. TI Unpacking the association: Individual differences in the relation of prenatal exposure to cigarettes and disruptive behavior phenotypes SO NEUROTOXICOLOGY AND TERATOLOGY LA English DT Article DE Prenatal exposure to cigarettes; Disruptive behavior; Parental responsiveness; Sex differences; Developmental pathways; Maternal smoking ID CHILDHOOD PHYSICAL AGGRESSION; SELF-REPORTED MEASURES; MATERNAL SMOKING; ANTISOCIAL-BEHAVIOR; CONDUCT PROBLEMS; DEVELOPMENTAL PSYCHOPATHOLOGY; EXTERNALIZING PROBLEMS; PREGNANCY SMOKING; LATE ADOLESCENCE; BIRTH-WEIGHT AB Prenatal exposure to cigarettes has been robustly associated with disruptive behavior in diverse samples and across developmental periods. In this paper we aim to elucidate exposure related behavioral phenotypes and developmental pathways by testing: (a) differential associations of exposure and four disruptive behavior dimensional phenotypes: Aggression, Noncompliance, Temper Loss and Low Concern for Others; and (b) moderation of these pathways including sex differences and moderation by parental responsive engagement. Participants were 211 teens and their parents from the East Boston Family Study (EBFS), an adolescent follow-up of a pregnancy cohort over-sampled for exposure. A best estimate serum cotinine corrected score was used to characterize exposure. In multivariate models controlling for parental antisocial behavior, family adversity and secondhand exposure, exposure uniquely predicted Aggression and Noncompliance. Paternal responsiveness moderated exposure effects on disruptive behavior. There were no sex differences in these patterns. Phenotypic findings suggest the possibility of specific neural mechanisms. In conjunction with prior research, protective effects of parental responsiveness occurring as late as adolescence point to the potential benefit of parenting-based prevention efforts to reduce risk to exposed offspring. (C) 2010 Elsevier Inc. All rights reserved. C1 [Wakschlag, Lauren S.; Burns, James] Northwestern Univ, Feinberg Sch Med, Dept Med Social Sci, Chicago, IL 60611 USA. [Henry, David B.] Univ Illinois, Sch Publ Hlth, Inst Hlth Res & Policy, Chicago, IL USA. [Blair, R. James R.] NIMH, Mood & Anxiety Program, Bethesda, MD 20892 USA. [Dukic, Vanja] Univ Chicago, Sch Med, Dept Hlth Studies, Chicago, IL 60637 USA. [Pickett, Kate E.] Univ York, Dept Hlth Sci, York YO10 5DD, N Yorkshire, England. [Pickett, Kate E.] Univ York, Hull York Med Sch, York YO10 5DD, N Yorkshire, England. RP Wakschlag, LS (reprint author), Northwestern Univ, Feinberg Sch Med, Dept Med Social Sci, Abbott Hall,Suite 729,710 N Lake Shore Dr, Chicago, IL 60611 USA. EM lauriew@northwestern.edu OI Dukic, Vanja/0000-0002-0348-0834 FU Department of Health [CSA/03/07/014]; NIDA NIH HHS [R01 DA023653, R01 DA015223, R01 DA015223-01A1, R01 DA015223-02, R01 DA015223-03, R01 DA015223-04, R01 DA015223-05, R01 DA015223-06, R01 DA023653-01A2, R01 DA023653-02, R01 DA023653-03] NR 75 TC 12 Z9 13 U1 5 U2 11 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0892-0362 J9 NEUROTOXICOL TERATOL JI Neurotoxicol. Teratol. PD JAN-FEB PY 2011 VL 33 IS 1 SI SI BP 145 EP 154 DI 10.1016/j.ntt.2010.07.002 PG 10 WC Neurosciences; Toxicology SC Neurosciences & Neurology; Toxicology GA 724XN UT WOS:000287609800017 PM 21256429 ER PT J AU LaGasse, LL Wouldes, T Newman, E Smith, LM Shah, RZ Derauf, C Huestis, MA Arria, AM Della Grotta, S Wilcox, T Lester, BM AF LaGasse, Linda L. Wouldes, Trecia Newman, Elana Smith, Lynne M. Shah, Rizwan Z. Derauf, Chris Huestis, Marilyn A. Arria, Amelia M. Della Grotta, Sheri Wilcox, Tara Lester, Barry M. TI Prenatal methamphetamine exposure and neonatal neurobehavioral outcome in the USA and New Zealand SO NEUROTOXICOLOGY AND TERATOLOGY LA English DT Article DE Prenatal exposure; Methamphetamine; Neurodevelopment; Meconium ID UTERO COCAINE EXPOSURE; MATERNAL LIFE-STYLE; IN-UTERO; NEWBORN NEUROBEHAVIOR; SUBSTANCE EXPOSURE; INFANT DEVELOPMENT; DEVELOPING BRAIN; PREGNANT-WOMEN; CHILDREN; DOPAMINE AB Background: Methamphetamine (MA) use among pregnant women is a world-wide problem, but little is known of its impact on exposed infants. Design: The prospective, controlled longitudinal Infant Development, Environment and Lifestyle (IDEAL) study of prenatal MA exposure from birth to 36 months was conducted in the US and NZ. The US cohort has 183 exposed and 196 comparison infants; the NZ cohort has 85 exposed and 95 comparison infants. Exposure was determined by self-report and meconium assay with alcohol, marijuana, and tobacco exposures present in both groups. The NICU Neurobehavior Scale (NNNS) was administered within 5 days of life. NNNS summary scores were analyzed for exposure including heavy exposure and frequency of use by trimester and dose-response relationship with the amphetamine analyte. Results: MA exposure was associated with poorer quality of movement, more total stress/abstinence, physiological stress, and CNS stress with more nonoptimal reflexes in NZ but not in the USA. Heavy MA exposure was associated with lower arousal and excitability. First trimester MA use predicted more stress and third trimester use more lethargy and hypotonicity. Dose-response effects were observed between amphetamine concentration in meconium and CNS stress. Conclusion: Across cultures, prenatal MA exposure was associated with a similar neurobehavioral pattern of under arousal, low tone, poorer quality of movement and increased stress. (C) 2010 Elsevier Inc. All rights reserved. C1 [LaGasse, Linda L.; Della Grotta, Sheri; Wilcox, Tara; Lester, Barry M.] Brown Univ, Women & Infants Hosp, Warren Alpert Med Sch, Ctr Study Children Risk, Providence, RI USA. [Wouldes, Trecia] Univ Auckland, Dept Psychol Med, Auckland 1, New Zealand. [Newman, Elana] Univ Tulsa, Dept Psychol, Tulsa, OK 74104 USA. [Smith, Lynne M.] Univ Calif Los Angeles, David Geffen Sch Med, Los Angeles, CA 90095 USA. [Smith, Lynne M.] Harbor UCLA Med Ctr, Los Angeles Biomed Inst, Los Angeles, CA USA. [Shah, Rizwan Z.] Blank Hosp Reg Child Protect Ctr Iowa Hlth, Des Moines, IA USA. [Derauf, Chris] Univ Hawaii, John A Burns Sch Med, Honolulu, HI 96822 USA. [Huestis, Marilyn A.] NIDA, Intramural Res Program, NIH, Baltimore, MD USA. [Arria, Amelia M.] Univ Maryland, Ctr Subst Abuse Res CESAR, College Pk, MD 20742 USA. RP LaGasse, LL (reprint author), Brown Ctr Study Children Risk, 101 Dudley St, Providence, RI 02905 USA. EM Linda_Lagasse@brown.edu OI Arria, Amelia/0000-0002-6360-9265; Wouldes, Trecia/0000-0002-6609-8464 FU National Institute on Drug Abuse [R01DA021757, R01DA014948]; Auckland Medical Research Foundation; National Center on Research Resources [M01RR00426, P20RR11091]; National Institutes of Health FX This study was supported from the National Institute on Drug Abuse (LLL: R01DA021757; BML: R01DA014948) and in part from the Auckland Medical Research Foundation (TW), the National Center on Research Resources (M01RR00426; P20RR11091) and the National Institutes of Health Intramural Research Program (MAH). We thank Carolyn Ho, Jennie Rodgers, Jo Cliffe, and Heather Stewart in NZ and Matt Hinckley, Jean Twomey, Darlene Decesare, Fatima Guerra and Hai Lin in the US for their assistance on this international collaboration as well as the staff at the IDEAL US sites. NR 58 TC 36 Z9 36 U1 3 U2 19 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0892-0362 J9 NEUROTOXICOL TERATOL JI Neurotoxicol. Teratol. PD JAN-FEB PY 2011 VL 33 IS 1 SI SI BP 166 EP 175 DI 10.1016/j.ntt.2010.06.009 PG 10 WC Neurosciences; Toxicology SC Neurosciences & Neurology; Toxicology GA 724XN UT WOS:000287609800019 PM 20615464 ER PT J AU Smith, LM LaGasse, LL Derauf, C Newman, E Shah, R Haning, W Arria, A Huestis, M Strauss, A Della Grotta, S Dansereau, LM Lin, H Lester, BM AF Smith, Lynne M. LaGasse, Linda L. Derauf, Chris Newman, Elana Shah, Rizwan Haning, William Arria, Amelia Huestis, Marilyn Strauss, Arthur Della Grotta, Sheri Dansereau, Lynne M. Lin, Hai Lester, Barry M. TI Motor and cognitive outcomes through three years of age in children exposed to prenatal methamphetamine SO NEUROTOXICOLOGY AND TERATOLOGY LA English DT Article DE Prenatal exposure; Neurodevelopment; Bayley; Peabody ID MATERNAL LIFE-STYLE; COCAINE EXPOSURE; IN-UTERO; INFANT DEVELOPMENT; INTRAUTERINE GROWTH; RAT PUPS; PREGNANCY; AMPHETAMINE; ENVIRONMENT; TERM AB Background: Methamphetamine (MA) use among pregnant women is an increasing problem in the United States. The impact of prenatal MA exposure on development in childhood is unknown. Objective: To examine the effects of prenatal MA exposure on motor and cognitive development in children at 1, 2, and 3 years of age. Design/methods: IDEAL enrolled 412 mother-infant pairs at four sites (Tulsa OK, Des Moines IA, Los Angeles CA, and Honolulu HI). MA subjects (n = 204) were identified by self report or GC/MS confirmation of amphetamine and metabolites in infant meconium. Comparison subjects (n = 208) were matched (race, birth weight, maternal education, and type of insurance), denied amphetamine use, and had a negative meconium screen. Both groups included prenatal alcohol, tobacco and marijuana use, but excluded use of opiates, lysergic acid diethylamide, phencyclidine or cocaine only. The Peabody Developmental Motor Scales (PDMS-2) were administered to the infants at the 1 and 3 year visits. This analysis includes a subsample (n = 350) of the IDEAL study with completed 1 and/or 3 year visits (n = 330 and 281, respectively). At each annual visit we also conducted the Bayley Scales of Infant Development (BSID-II) as a general evaluation of mental and motor development. The BSID-II analysis includes a subsample (n = 356) of the IDEAL study with completed 1, 2, and/or 3 year visits (n = 331, 288, and 278 respectively). GLM analysis conducted on the PDMS-2 and BSID-II examined the effects of MA exposure and heavy MA exposure (>= 3 days of use/week), with and without covariates. Longitudinal analyses were used to examine the effects of MA exposure on changes in motor and cognitive performance over time. Results: Heavy MA exposure was associated with significantly lower grasping scores than some and no use at 1 year (P = 0.018). In longitudinal analysis, lower grasping scores associated with any MA exposure and heavy exposure persisted to 3 years. There were no effects of MA exposure, including heavy exposure, on the Bayley Mental Development Index (MDI) or Psychomotor Development Index (PDI) at any or across age. Conclusions: There were no differences in cognition as assessed by the BSID-II between the groups. There was a subtle MA exposure effect on fine motor performance at 1 year with the poorest performance observed in the most heavily exposed children. By 3 years, no differences in fine motor performance were observed. These findings suggest MA exposure has modest motor effects at 1 year that are mostly resolved by 3 years. (C) 2010 Elsevier Inc. All rights reserved. C1 [Smith, Lynne M.] Harbor UCLA Med Ctr, Los Angeles Biomed Inst, Torrance, CA 90502 USA. [Smith, Lynne M.] Univ Calif Los Angeles, David Geffen Sch Med, Los Angeles, CA 90095 USA. [LaGasse, Linda L.; Della Grotta, Sheri; Dansereau, Lynne M.; Lin, Hai; Lester, Barry M.] Brown Univ, Women & Infants Hosp, Warren Alpert Med Sch, Ctr Study Children Risk, Providence, RI USA. [Derauf, Chris; Haning, William] Univ Hawaii, John A Burns Sch Med, Honolulu, HI 96822 USA. [Newman, Elana] Univ Tulsa, Dept Psychol, Tulsa, OK 74104 USA. [Shah, Rizwan] Blank Hosp Reg Child Protect Ctr Iowa Hlth, Des Moines, IA USA. [Arria, Amelia] Univ Maryland, Ctr Subst Abuse Res CESAR, College Pk, MD 20742 USA. [Huestis, Marilyn] NIDA, Intramural Res Program, NIH, Baltimore, MD USA. [Strauss, Arthur] Long Beach Mem Med Ctr, Long Beach, CA USA. RP Smith, LM (reprint author), Harbor UCLA Med Ctr, Los Angeles Biomed Inst, 1124 W Carson St,Box 446, Torrance, CA 90502 USA. EM smith@labiomed.org OI Arria, Amelia/0000-0002-6360-9265 FU National Institute on Drug Abuse (NIDA) [R01DA021757, R01DA014948]; National Center on Research Resources [3 M01 RR00425, P20 RR11091] FX This study is part of the Infant Development, Environment and Lifestyle (IDEAL) Study, which was conducted with support from the National Institute on Drug Abuse (NIDA), R01DA021757 (Linda LaGasse, Ph.D.) and R01DA014948 (Barry Lester, Ph.D.) and in part by the National Center on Research Resources, Grant # 3 M01 RR00425 and P20 RR11091. NR 56 TC 23 Z9 24 U1 4 U2 15 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0892-0362 J9 NEUROTOXICOL TERATOL JI Neurotoxicol. Teratol. PD JAN-FEB PY 2011 VL 33 IS 1 SI SI BP 176 EP 184 DI 10.1016/j.ntt.2010.10.004 PG 9 WC Neurosciences; Toxicology SC Neurosciences & Neurology; Toxicology GA 724XN UT WOS:000287609800020 PM 21256431 ER PT J AU Kirby, AC Nager, CW Litman, HJ FitzGerald, MP Kraus, S Norton, P Sirls, L Rickey, L Wilson, T Dandreo, KJ Shepherd, J Zimmern, P AF Kirby, Anna C. Nager, Charles W. Litman, Heather J. FitzGerald, Mary P. Kraus, Stephen Norton, Peggy Sirls, Larry Rickey, Leslie Wilson, Tracey Dandreo, Kimberly J. Shepherd, Jonathan Zimmern, Philippe CA Urinary Incontinence Treatment TI Perineal Surface Electromyography Does Not Typically Demonstrate Expected Relaxation During Normal Voiding SO NEUROUROLOGY AND URODYNAMICS LA English DT Article DE electromyography; pelvic floor; stress urinary incontinence; urethra; urodynamics; voiding dysfunction ID PRESSURE-FLOW; STRESS-INCONTINENCE; MUSCLES; WOMEN; OBSTRUCTION; ELECTRODES; CYSTOMETRY AB Aims: To describe perineal surface patch electromyography (EMG) activity during urodynamics (UDS) and compare activity between filling and voiding phases and to assess for a relationship between preoperative EMG activity and postoperative voiding symptoms. Methods: 655 women underwent standardized preoperative UDS that included perineal surface EMG prior to undergoing surgery for stress urinary incontinence. Pressure-flow studies were evaluated for abdominal straining and interrupted flow. Quantitative EMG values were extracted from 10 predetermined time-points and compared between fill and void. Qualitative EMG activity was assessed for the percent of time EMG was active during fill and void and for the average amplitude of EMG during fill compared to void. Postoperative voiding dysfunction was defined as surgical revision or catheterization more than 6 weeks after surgery. Fisher's exact test with a 5% two-sided significance level was used to assess differences in EMG activity and postoperative voiding dysfunction. Results: 321 UDS had interpretable EMG studies, of which 131 (41%) had EMG values at all 10 predetermined and annotated time-points. Quantitative and qualitative EMG signals during flow were usually greater than during fill. The prevalence of postoperative voiding dysfunction in subjects with higher preoperative EMG activity during void was not significantly different. Results were similar in the 42 subjects who had neither abdominal straining during void nor interrupted flow. Conclusions: Perineal surface patch EMG did not measure expected pelvic floor and urethral sphincter relaxation during voiding. Preoperative EMG did not predict patients at risk for postoperative voiding dysfunction. Neurourol. Urodynam. 30:1591-1596, 2011. (C) 2011 Wiley Periodicals, Inc. C1 [Kirby, Anna C.; Nager, Charles W.] Univ Calif San Diego, Dept Reprod Med, San Diego, CA 92103 USA. [Litman, Heather J.; Dandreo, Kimberly J.] New England Res Inst, Watertown, MA 02172 USA. [FitzGerald, Mary P.] Loyola Univ, Med Ctr, Dept Obstet & Gynecol, Maywood, IL 60153 USA. [Kraus, Stephen] Univ Texas Hlth Sci Ctr San Antonio, Dept Urol, San Antonio, TX 78229 USA. [Norton, Peggy] Univ Utah, Dept Obstet & Gynecol, Salt Lake City, UT USA. [Sirls, Larry] William Beaumont Hosp, Dept Urol, Royal Oak, MI 48072 USA. [Rickey, Leslie] Univ Maryland, Dept Urol, Baltimore, MD 21201 USA. [Wilson, Tracey] Univ Alabama, Dept Urol, Birmingham, AL USA. [Shepherd, Jonathan] Univ Pittsburgh, Magee Womens Hosp, Dept Obstet Gynecol & Reprod Sci, Pittsburgh, PA 15213 USA. [Zimmern, Philippe] Univ Texas SW, Dept Urol, Dallas, TX USA. [Urinary Incontinence Treatment] NIDDK, NIH, Bethesda, MD USA. RP Nager, CW (reprint author), 9350 Campus Point Dr,Suite 2A,Mail Code 0974, La Jolla, CA 92037 USA. EM cnager@ucsd.edu FU National Institute of Diabetes and Digestive and Kidney Diseases [U01 DK58225, U01 DK58229, U01 DK58234, U01 DK58231, U01 DK60379, U01 DK60380, U01 DK60393, U01 DK60395, U01 DK60397, U01 DK60401]; National Institute of Child Health and Human Development; Office of Research in Women's Health of the National Institutes of Health FX Grant sponsor: National Institute of Diabetes and Digestive and Kidney Diseases; Grant numbers: U01 DK58225; U01 DK58229; U01 DK58234; U01 DK58231; U01 DK60379; U01 DK60380; U01 DK60393; U01 DK60395; U01 DK60397; U01 DK60401; Grant sponsor: National Institute of Child Health and Human Development; Grant sponsor: Office of Research in Women's Health of the National Institutes of Health. NR 20 TC 1 Z9 1 U1 1 U2 2 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0733-2467 J9 NEUROUROL URODYNAM JI Neurourol. Urodyn. PY 2011 VL 30 IS 8 BP 1591 EP 1596 DI 10.1002/nau.21080 PG 6 WC Urology & Nephrology SC Urology & Nephrology GA 840FT UT WOS:000296425200040 PM 21560157 ER PT J AU Warnick, JE LaPorte, JL Kalueff, AV AF Warnick, Jason E. LaPorte, Justin L. Kalueff, Allan V. TI Domain interplay in mice and men: New possibilities for the "natural kinds" theory of emotion SO NEW IDEAS IN PSYCHOLOGY LA English DT Article DE Domain interplay; Behavioral phenotype; Emotion; Natural kind; Animal model ID ANXIETY-DEPRESSION CONTINUUM; ANIMAL-MODELS; NEUROPHENOTYPING RESEARCH; ENVIRONMENT INTERACTIONS; MOUSE; DISORDERS; AUTISM; BEHAVIORS; RELEVANT; GENETICS AB The recent challenge to the long-held assumption that emotions are natural kinds (i.e., discreet naturally-distinguishable phenomena) has raised the necessity for a closer look into the nature of affective research. If emotions are not natural kinds, there will be widespread consequences for the theoretical foundations of behavioral neuroscience and grave implications for the validity of animal models of emotion and affective disorders. This paper presents the evidence against the hypothesis of emotions as natural kinds, and offers the "domain-interplay" concept as a novel and effective experimental method for establishing the theoretical rationale of non-human animal research in the neurosciences. (C) 2010 Elsevier Ltd. All rights reserved. C1 [Warnick, Jason E.] Arkansas Tech Univ, Dept Behav Sci, Russellville, AR 72801 USA. [LaPorte, Justin L.] NIMH, Clin Sci Lab, Bethesda, MD 20892 USA. [Kalueff, Allan V.] Tulane Univ, Sch Med, Dept Pharmacol, New Orleans, LA 70112 USA. RP Warnick, JE (reprint author), Arkansas Tech Univ, Dept Behav Sci, Russellville, AR 72801 USA. EM jwarnick@atu.edu RI Warnick, Jason/C-5305-2015 OI Warnick, Jason/0000-0002-9632-0505 NR 44 TC 3 Z9 3 U1 0 U2 2 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0732-118X J9 NEW IDEAS PSYCHOL JI New Ideas Psychol. PD JAN-APR PY 2011 VL 29 IS 1 BP 49 EP 56 DI 10.1016/j.newideapsych.2010.01.001 PG 8 WC Psychology, Multidisciplinary; Psychology, Experimental SC Psychology GA 682XS UT WOS:000284436900005 ER PT S AU Nagababu, E Rifkind, JM AF Nagababu, Enika Rifkind, Joseph M. BE McCarthy, HO Coulter, JA TI Determination of S-Nitrosothiols in Biological Fluids by Chemiluminescence SO NITRIC OXIDE: METHODS AND PROTOCOLS SE Methods in Molecular Biology LA English DT Article; Book Chapter DE S-nitrosothiols; nitric oxide; ozone-based chemiluminescence assay; plasma; red blood cells ID NITRIC-OXIDE; N-NITROSO; PLASMA; REDUCTION; PROTEINS AB S-nitrosothiols present in nanomolar concentrations in cells and body fluids play an important role in vasodilation, in preventing platelet aggregation, leukocyte adhesion, and for cellular signaling. However, because of the low levels of s-nitrosothiols and interference with other nitric oxide species, reliable assays that measure both high molecular weight and low molecular weight s-nitrosothiols in plasma and red blood cells have been difficult to develop. We have previously developed a sensitive method using Cu(II)-ascorbic acid at a neutral pH, which was specific for s-nitrosothiols without interference of nitrite or other NOx species. However, due to neutral pH foaming, this method was not suitable for determinations in plasma or red blood cells with high protein content. This method has now been modified by using copper (II) chloride (CuCl2) and ascorbic acid in glacial acetic acid. The low pH solves the foaming problem. However, protonation of nitrite under acidic conditions facilitates the formation of s-nitrosothiols. For this method to specifically measure s-nitrosothiols in the sample, the unreacted thiols are blocked by reacting with N-ethylmaleimide and nitrite is blocked by reacting with acidified sulfanilamide before being analyzed by chemiluminescence. Using this method, s-nitrosothiols have been determined in the range of 2 nM to 26 nM (mean +/- SE = 10.18 +/- 2.1) in plasma and up to 88.1 nM (mean +/- SE = 51.27 +/- 10.5) in red blood cells. C1 [Nagababu, Enika; Rifkind, Joseph M.] NIA, Mol Dynam Sect, NIH, Baltimore, MD 21224 USA. RP Nagababu, E (reprint author), NIA, Mol Dynam Sect, NIH, Baltimore, MD 21224 USA. NR 15 TC 12 Z9 15 U1 0 U2 9 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DR, STE 208, TOTOWA, NJ 07512-1165 USA SN 1064-3745 BN 978-1-61737-963-5 J9 METHODS MOL BIOL JI Methods Mol. Biol. PY 2011 VL 704 BP 27 EP 37 DI 10.1007/978-1-61737-964-2_3 D2 10.1007/978-1-61737-964-2 PG 11 WC Biochemical Research Methods; Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA BSV21 UT WOS:000285893500003 PM 21161627 ER PT S AU Piknova, B Schechter, AN AF Piknova, Barbora Schechter, Alan N. BE McCarthy, HO Coulter, JA TI Measurement of Nitrite in Blood Samples Using the Ferricyanide-Based Hemoglobin Oxidation Assay SO NITRIC OXIDE: METHODS AND PROTOCOLS SE Methods in Molecular Biology LA English DT Article; Book Chapter DE Nitrite; hemoglobin; red blood cell; chemiluminescence ID BIOLOGICAL SAMPLES; S-NITROSOTHIOLS; PLASMA NITRITE; CHEMILUMINESCENCE; OXIDE; METABOLITES; NITRATE; NO AB Nitrite is currently recognized as a biomarker of the state of nitric oxide metabolism. Therefore, assessing nitrite levels in various organs and compartments is an important issue. As nitrite levels in most organs and tissues ate low (in high nanomolar or low micromolar range) several new sensitive methods for quantifying nitrite in various biological samples have been developed. Chemiluminescence, combined with triiodide reducing solution, is currently considered the most sensitive method, allowing quantification in the low nanomolar range of nitrite concentrations. Here, we present an overview of chemiluminescence-based determination of nitrite in blood and blood compartments red blood cells and plasma. We also explain how to preserve the original physiological nitrite concentration in nitrite-hostile environments, such as an excess of hemoglobin in blood. C1 [Piknova, Barbora; Schechter, Alan N.] NIDDK, Mol Med Branch, NIH, Bethesda, MD 20892 USA. RP Piknova, B (reprint author), NIDDK, Mol Med Branch, NIH, Bethesda, MD 20892 USA. OI Schechter, Alan N/0000-0002-5235-9408 FU Intramural NIH HHS [ZIA DK025093-14, ZIA DK025104-06] NR 13 TC 7 Z9 7 U1 2 U2 3 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DR, STE 208, TOTOWA, NJ 07512-1165 USA SN 1064-3745 BN 978-1-61737-963-5 J9 METHODS MOL BIOL JI Methods Mol. Biol. PY 2011 VL 704 BP 39 EP 56 DI 10.1007/978-1-61737-964-2_4 D2 10.1007/978-1-61737-964-2 PG 18 WC Biochemical Research Methods; Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA BSV21 UT WOS:000285893500004 PM 21161628 ER PT S AU O'Carroll, IP Dos Santos, PC AF O'Carroll, Ina P. Dos Santos, Patricia C. BE Ribbe, MW TI Genomic Analysis of Nitrogen Fixation SO NITROGEN FIXATION: METHODS AND PROTOCOLS SE Methods in Molecular Biology LA English DT Article; Book Chapter DE Genome sequencing; genome scanning; genomics; Azotobacter vinelandii; nitrogen fixation ID IRON-MOLYBDENUM COFACTOR; AZOTOBACTER-VINELANDII; MUTATIONAL ANALYSIS; STRUCTURAL GENES; MOFE PROTEIN; PSEUDOMONAS-STUTZERI; NUCLEOTIDE-SEQUENCE; INDEPENDENT NITROGENASES; RESPIRATORY PROTECTION; CONTROLLED EXPRESSION AB Advances in sequencing technology in the past decade have enabled the sequencing of genomes of thousands of organisms including diazotrophs. Genomics have enabled thorough analysis of the gene organization of nitrogen-fixing species, the identification of new genes involved in nitrogen fixation, and the identification of new diazotrophic species. This chapter reviews key characteristics of nitrogen-fixing genomes and methods to identify and analyze genomes of new diazotrophs using genome scanning. This chapter refers to Azotobacter vinelandii, a well-studied nitrogen-fixing organism, as a model for studying nitrogen-fixing genomes. We discuss the main nitrogen fixation genes as well as accessory genes that contribute to diazotrophy. We also review approaches that can be used to modify genomes in order to study nitrogen fixation at the genetic, biochemical, and biophysical level. C1 [O'Carroll, Ina P.] NCI, HIV Drug Resistance Program, Frederick, MD 21701 USA. [Dos Santos, Patricia C.] Wake Forest Univ, Dept Chem, Wiston Salem, NC USA. RP O'Carroll, IP (reprint author), NCI, HIV Drug Resistance Program, Frederick, MD 21701 USA. OI Dos Santos, Patricia/0000-0002-3364-0931 NR 71 TC 4 Z9 4 U1 2 U2 7 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DR, STE 208, TOTOWA, NJ 07512-1165 USA SN 1064-3745 BN 978-1-61779-193-2 J9 METHODS MOL BIOL JI Methods Mol. Biol. PY 2011 VL 766 BP 49 EP 65 DI 10.1007/978-1-61779-194-9_4 D2 10.1007/978-1-61779-194-9 PG 17 WC Biochemical Research Methods; Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA BWP54 UT WOS:000294445200004 PM 21833860 ER PT J AU Hu, TCC Chuang, KH Yanasak, N Koretsky, A AF Hu, Tom C. -C. Chuang, Kai-Hsiang Yanasak, Nathan Koretsky, Alan TI Relationship between blood and myocardium manganese levels during manganese-enhanced MRI (MEMRI) with T-1 mapping in rats SO NMR IN BIOMEDICINE LA English DT Article DE T-1 mapping; cardiac MRI; rat; heart; manganese; imaging ID TRISODIUM MNDPDP INJECTION; RESONANCE-IMAGING MEMRI; III CLINICAL-TRIALS; INFARCTED MYOCARDIUM; CALCIUM-CHANNEL; CONTRAST AGENTS; MURINE MODEL; HEPATIC MRI; HEART; VIABILITY AB Manganese ions (Mn2+) enter viable myocardial cells via voltage-gated calcium channels. Because of its shortening of T-1 and its relatively long half-life in cells, Mn2+ can serve as an intracellular molecular contrast agent to study indirect calcium influx into the myocardium. One major concern in using Mn2+ is its sensitivity over a limited range of concentrations employing T-1-weighted images for visualization, which limits its potential in quantitative techniques. Therefore, this study assessed the implementation of a T-1 mapping method for cardiac manganese-enhanced MRI to enable a quantitative estimate of the influx of Mn2+ over a wide range of concentrations in male Sprague-Dawley rats. This MRI method was used to compare the relationship between T-1 changes in the heart as a function of myocardium and blood Mn2+ levels. Results showed a biphasic relationship between Delta R-1 and the total Mn2+ infusion dose. Nonlinear relationships were observed between the total Mn2+ infusion dose versus blood levels and left ventricular free wall Delta R-1. At low blood levels of Mn2+, there was proportionally less cardiac enhancement seen than at higher levels of blood Mn2+. We hypothesize that Mn2+ blood levels increase as a result of rate-limiting excretion by the liver and kidneys at these higher Mn2+ doses. Copyright (C) 2010 John Wiley & Sons, Ltd. C1 [Hu, Tom C. -C.; Yanasak, Nathan] Med Coll Georgia, Dept Radiol, Augusta, GA 30912 USA. [Hu, Tom C. -C.; Chuang, Kai-Hsiang; Koretsky, Alan] NINDS, Lab Funct & Mol Imaging, NIH, Bethesda, MD 20892 USA. RP Hu, TCC (reprint author), Med Coll Georgia, Dept Radiol, 1410 Laney Walker Blvd,CN-3155, Augusta, GA 30912 USA. EM thu@mail.mcg.edu RI Koretsky, Alan/C-7940-2015; OI Koretsky, Alan/0000-0002-8085-4756; Chuang, Kai-Hsiang/0000-0002-8356-0657 FU National Institutes of Health (NIH); National Institute of Neurological Disorders and Stroke (NINDS) FX This research was supported (in part) by the Intramural Research Program of the National Institutes of Health (NIH) and the National Institute of Neurological Disorders and Stroke (NINDS). The authors thank N. Bouraoud, D. Straus, D. Despres, G. A. MacGowan, C. Du, K. Hendrich, M.-T. Li and A. Schumacher for stimulating discussions, inputs and technical assistance. The authors would also like to thank Mrs Mary Barbier for editorial assistance with this paper. NR 34 TC 7 Z9 7 U1 0 U2 2 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0952-3480 J9 NMR BIOMED JI NMR Biomed. PD JAN PY 2011 VL 24 IS 1 BP 46 EP 53 DI 10.1002/nbm.1554 PG 8 WC Biophysics; Radiology, Nuclear Medicine & Medical Imaging; Spectroscopy SC Biophysics; Radiology, Nuclear Medicine & Medical Imaging; Spectroscopy GA 718GY UT WOS:000287110300005 PM 20665900 ER PT J AU Bandele, OJ Wang, XT Campbell, MR Pittman, GS Bell, DA AF Bandele, Omari J. Wang, Xuting Campbell, Michelle R. Pittman, Gary S. Bell, Douglas A. TI Human single-nucleotide polymorphisms alter p53 sequence-specific binding at gene regulatory elements SO NUCLEIC ACIDS RESEARCH LA English DT Article ID BREAST-CANCER CELLS; TRANSCRIPTION-FACTOR; DNA-DAMAGE; HUMAN GENOME; RESPONSE-ELEMENTS; PROMOTER; SITES; EXPRESSION; NETWORK; TARGETS AB p53 coordinates the expression of an intricate network of genes in response to stress signals. Sequence-specific DNA binding is essential for p53-mediated tumor suppression. We evaluated the impact of single-nucleotide polymorphisms (SNPs) in p53 response elements (p53RE) on DNA binding and gene expression in response to DNA damage. Using a bioinformatics approach based on incorporating p53 binding strength into a position weight matrix, we selected 32 SNPs in putative and validated p53REs. The microsphere assay for protein-DNA binding (MAPD) and allele-specific expression analysis was employed to assess the impact of SNPs on p53-DNA binding and gene expression, respectively. Comparing activated p53 binding in nuclear extracts from doxorubicin- or ionizing radiation (IR)-treated human cells, we observed little difference in binding profiles. Significant p53 binding was observed for most polymorphic REs and several displayed binding comparable to the p21 RE. SNP alleles predicted to lower p53 binding indeed reduced binding in 25 of the 32 sequences. Chromatin immunoprecipitation-sequencing in lymphoblastoid cells confirmed p53 binding to seven polymorphic p53 REs in response to doxorubicin. In addition, five polymorphisms were associated with altered gene expression following doxorubicin treatment. Our findings demonstrate an effective strategy to identify and evaluate SNPs that may alter p53-mediated stress responses. C1 [Bandele, Omari J.; Wang, Xuting; Campbell, Michelle R.; Pittman, Gary S.; Bell, Douglas A.] Natl Inst Environm Hlth Sci, Environm Genom Grp, Mol Genet Lab, NIH, Res Triangle Pk, NC 27709 USA. RP Bell, DA (reprint author), Natl Inst Environm Hlth Sci, Environm Genom Grp, Mol Genet Lab, NIH, Res Triangle Pk, NC 27709 USA. EM bell1@niehs.nih.gov OI Wang, Xuting/0000-0001-6781-8008 FU National Institute of Environmental Health Sciences, National Institutes of Health [ZO1-ES-100475-M-0001, ZO1-ES065079-15]; National Institute of Environmental Health Sciences FX The Intramural Research Program of the National Institute of Environmental Health Sciences, National Institutes of Health (ZO1-ES-100475-M-0001 and ZO1-ES065079-15). Funding for open access charge: The Intramural Research Program, National Institute of Environmental Health Sciences. NR 54 TC 16 Z9 17 U1 0 U2 5 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0305-1048 J9 NUCLEIC ACIDS RES JI Nucleic Acids Res. PD JAN PY 2011 VL 39 IS 1 BP 178 EP 189 DI 10.1093/nar/gkq764 PG 12 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 703VD UT WOS:000286008500019 PM 20817676 ER PT J AU Midon, M Schafer, P Pingoud, A Ghosh, M Moon, AF Cuneo, MJ London, RE Meiss, G AF Midon, Marika Schaefer, Patrick Pingoud, Alfred Ghosh, Mahua Moon, Andrea F. Cuneo, Matthew J. London, Robert E. Meiss, Gregor TI Mutational and biochemical analysis of the DNA-entry nuclease EndA from Streptococcus pneumoniae SO NUCLEIC ACIDS RESEARCH LA English DT Article ID GROUP-A STREPTOCOCCUS; NEUTROPHIL EXTRACELLULAR TRAPS; SERRATIA-MARCESCENS NUCLEASE; SUGAR-NONSPECIFIC NUCLEASE; RAY SOLUTION SCATTERING; GENETIC TRANSFORMATION; BACILLUS-SUBTILIS; ESCHERICHIA-COLI; MECHANISM; ANABAENA AB EndA is a membrane-attached surface-exposed DNA-entry nuclease previously known to be required for genetic transformation of Streptococcus pneumoniae. More recent studies have shown that the enzyme also plays an important role during the establishment of invasive infections by degrading extracellular chromatin in the form of neutrophil extracellular traps (NETs), enabling streptococci to overcome the innate immune system in mammals. As a virulence factor, EndA has become an interesting target for future drug design. Here we present the first mutational and biochemical analysis of recombinant forms of EndA produced either in a cell-free expression system or in Escherichia coli. We identify His160 and Asn191 to be essential for catalysis and Asn182 to be required for stability of EndA. The role of His160 as the putative general base in the catalytic mechanism is supported by chemical rescue of the H160A variant of EndA with imidazole added in excess. Our study paves the way for the identification and development of protein or low-molecular-weight inhibitors for EndA in future high-throughput screening assays. C1 [Midon, Marika; Schaefer, Patrick; Pingoud, Alfred; Meiss, Gregor] Univ Giessen, Inst Biochem, D-35392 Giessen, Germany. [Ghosh, Mahua] Indian Inst Sci Educ & Res, Mohanpur 741252, W Bengal, India. [Moon, Andrea F.; Cuneo, Matthew J.; London, Robert E.] NIEHS, Struct Biol Lab, NIH, Res Triangle Pk, NC 27709 USA. RP Meiss, G (reprint author), Univ Giessen, Inst Biochem, Heinrich Buff Ring 58, D-35392 Giessen, Germany. EM gregor.meiss@chemie.bio.uni-giessen.de RI ID, BioCAT/D-2459-2012; OI Cuneo, Matthew/0000-0002-1475-6656 FU United States Department of Energy, Office of Science, Office of Basic Energy Sciences [DE-AC02-98CH10886, W-31-109-Eng-38]; German Research Foundation (DFG); 'Excellence Cluster Cardio-Pulmonary System' (ECCPS); Dr -Herbert-Stolzenberg-Stiftung of the Justus-Liebig-University Giessen FX The authors would like to thank the laboratory of Dr Lin Yang of the X9 beamline, at the National Synchrotron Light Source at Brookhaven National Laboratory and Dr Liang Guo of the 18-ID BioCat Beamline, at the Advanced Photon Source at the Argonne National Laboratory, for assistance with data collection. Use of the X9 beamline is supported by the United States Department of Energy, Office of Science, Office of Basic Energy Sciences, under Contract DE-AC02-98CH10886. Use of the Advanced Photon Source was supported by the U. S. Department of Energy, Office of Science, Office of Basic Energy Sciences, under Contract No W-31-109-Eng-38.; German Research Foundation (DFG); the 'Excellence Cluster Cardio-Pulmonary System' (ECCPS), and the Dr -Herbert-Stolzenberg-Stiftung of the Justus-Liebig-University Giessen. Funding for open access charge: German Research Foundation. NR 43 TC 13 Z9 15 U1 0 U2 2 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0305-1048 J9 NUCLEIC ACIDS RES JI Nucleic Acids Res. PD JAN PY 2011 VL 39 IS 2 BP 623 EP 634 DI 10.1093/nar/gkq802 PG 12 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 712OE UT WOS:000286675300027 PM 20846957 ER PT J AU Barrett, T Troup, DB Wilhite, SE Ledoux, P Evangelista, C Kim, IF Tomashevsky, M Marshall, KA Phillippy, KH Sherman, PM Muertter, RN Holko, M Ayanbule, O Yefanov, A Soboleva, A AF Barrett, Tanya Troup, Dennis B. Wilhite, Stephen E. Ledoux, Pierre Evangelista, Carlos Kim, Irene F. Tomashevsky, Maxim Marshall, Kimberly A. Phillippy, Katherine H. Sherman, Patti M. Muertter, Rolf N. Holko, Michelle Ayanbule, Oluwabukunmi Yefanov, Andrey Soboleva, Alexandra TI NCBI GEO: archive for functional genomics data sets-10 years on SO NUCLEIC ACIDS RESEARCH LA English DT Article ID GENE-EXPRESSION; INFORMATION AB A decade ago, the Gene Expression Omnibus (GEO) database was established at the National Center for Biotechnology Information (NCBI). The original objective of GEO was to serve as a public repository for high-throughput gene expression data generated mostly by microarray technology. However, the research community quickly applied microarrays to non-gene-expression studies, including examination of genome copy number variation and genome-wide profiling of DNA-binding proteins. Because the GEO database was designed with a flexible structure, it was possible to quickly adapt the repository to store these data types. More recently, as the microarray community switches to next-generation sequencing technologies, GEO has again adapted to host these data sets. Today, GEO stores over 20 000 microarray- and sequence-based functional genomics studies, and continues to handle the majority of direct high-throughput data submissions from the research community. Multiple mechanisms are provided to help users effectively search, browse, download and visualize the data at the level of individual genes or entire studies. This paper describes recent database enhancements, including new search and data representation tools, as well as a brief review of how the community uses GEO data. GEO is freely accessible at http://www.ncbi.nlm.nih.gov/geo/. C1 [Barrett, Tanya; Troup, Dennis B.; Wilhite, Stephen E.; Ledoux, Pierre; Evangelista, Carlos; Kim, Irene F.; Tomashevsky, Maxim; Marshall, Kimberly A.; Phillippy, Katherine H.; Sherman, Patti M.; Muertter, Rolf N.; Holko, Michelle; Ayanbule, Oluwabukunmi; Yefanov, Andrey; Soboleva, Alexandra] NIH, Natl Ctr Biotechnol Informat, Natl Lib Med, Bethesda, MD 20892 USA. RP Barrett, T (reprint author), NIH, Natl Ctr Biotechnol Informat, Natl Lib Med, 45 Ctr Dr, Bethesda, MD 20892 USA. EM barrett@ncbi.nlm.nih.gov FU National Institutes of Health, National Library of Medicine FX Funding for open access charge: The Intramural Research Program of the National Institutes of Health, National Library of Medicine. NR 22 TC 208 Z9 211 U1 1 U2 14 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0305-1048 J9 NUCLEIC ACIDS RES JI Nucleic Acids Res. PD JAN PY 2011 VL 39 SU 1 BP D1005 EP D1010 DI 10.1093/nar/gkq1184 PG 6 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 701PA UT WOS:000285831700158 ER PT J AU Benson, DA Karsch-Mizrachi, I Lipman, DJ Ostell, J Sayers, EW AF Benson, Dennis A. Karsch-Mizrachi, Ilene Lipman, David J. Ostell, James Sayers, Eric W. TI GenBank SO NUCLEIC ACIDS RESEARCH LA English DT Article ID DATABASE; GENERATION; ARCHIVE AB GenBank (R) is a comprehensive database that contains publicly available nucleotide sequences for more than 380 000 organisms named at the genus level or lower, obtained primarily through submissions from individual laboratories and batch submissions from large-scale sequencing projects, including whole genome shotgun (WGS) and environmental sampling projects. Most submissions are made using the web-based BankIt or standalone Sequin programs, and accession numbers are assigned by GenBank staff upon receipt. 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 NCBI Entrez retrieval system that integrates data from the major DNA and protein sequence databases along with taxonomy, genome, mapping, protein structure and domain information, and the biomedical journal literature via PubMed. BLAST provides sequence similarity searches of GenBank and other sequence databases. Complete bimonthly releases and daily updates of the GenBank database are available by FTP. To access GenBank and its related retrieval and analysis services, begin at the NCBI Homepage: www.ncbi.nlm.nih.gov. C1 [Benson, Dennis A.; Karsch-Mizrachi, Ilene; Lipman, David J.; Ostell, James; Sayers, Eric W.] Natl Lib Med, Natl Ctr Biotechnol Informat, NIH, Bethesda, MD 20894 USA. RP Sayers, EW (reprint author), Natl Lib Med, Natl Ctr Biotechnol Informat, NIH, 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 10 TC 392 Z9 404 U1 5 U2 19 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0305-1048 J9 NUCLEIC ACIDS RES JI Nucleic Acids Res. PD JAN PY 2011 VL 39 SU 1 BP D32 EP D37 DI 10.1093/nar/gkq1079 PG 6 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 701PA UT WOS:000285831700008 PM 21071399 ER PT J AU Cer, RZ Bruce, KH Mudunuri, US Yi, M Volfovsky, N Luke, BT Bacolla, A Collins, JR Stephens, RM AF Cer, Regina Z. Bruce, Kevin H. Mudunuri, Uma S. Yi, Ming Volfovsky, Natalia Luke, Brian T. Bacolla, Albino Collins, Jack R. Stephens, Robert M. TI Non-B DB: a database of predicted non-B DNA-forming motifs in mammalian genomes SO NUCLEIC ACIDS RESEARCH LA English DT Article ID SUPERCOILING IN-VIVO; CRUCIFORM FORMATION; HUMAN GENES; SEQUENCES; REARRANGEMENTS; COMPLEX; CONFORMATIONS; RECOMBINATION; REPEATS; BINDING AB Although the capability of DNA to form a variety of non-canonical (non-B) structures has long been recognized, the overall significance of these alternate conformations in biology has only recently become accepted en masse. In order to provide access to genome-wide locations of these classes of predicted structures, we have developed non-B DB, a database integrating annotations and analysis of non-B DNA-forming sequence motifs. The database provides the most complete list of alternative DNA structure predictions available, including Z-DNA motifs, quadruplex-forming motifs, inverted repeats, mirror repeats and direct repeats and their associated subsets of cruciforms, triplex and slipped structures, respectively. The database also contains motifs predicted to form static DNA bends, short tandem repeats and homo(purine center dot pyrimidine) tracts that have been associated with disease. The database has been built using the latest releases of the human, chimp, dog, macaque and mouse genomes, so that the results can be compared directly with other data sources. In order to make the data interpretable in a genomic context, features such as genes, single-nucleotide polymorphisms and repetitive elements (SINE, LINE, etc.) have also been incorporated. The database is accessed through query pages that produce results with links to the UCSC browser and a GBrowse-based genomic viewer. It is freely accessible at http://nonb.abcc.ncifcrf.gov. C1 [Cer, Regina Z.; Bruce, Kevin H.; Mudunuri, Uma S.; Yi, Ming; Volfovsky, Natalia; Luke, Brian T.; Bacolla, Albino; Collins, Jack R.; Stephens, Robert M.] NCI, Adv Biomed Comp Ctr, Informat Syst Program, SAIC Frederick Inc, Frederick, MD 21702 USA. [Bacolla, Albino] Univ Texas MD Anderson Canc Ctr, Dept Carcinogenesis, Div Sci Pk Res, Smithville, TX 78957 USA. RP Stephens, RM (reprint author), NCI, Adv Biomed Comp Ctr, Informat Syst Program, SAIC Frederick Inc, Frederick, MD 21702 USA. EM stephensr@mail.nih.gov RI Bacolla, Albino/N-3877-2013 OI Bacolla, Albino/0000-0003-0206-8423 FU Center for Biomedical Informatics and Information Technology (CBIIT)/Cancer Biomedical Informatics Grid (caBIG) ISRCE [09-260]; National Cancer Institute/National Institutes of Health [HHSN261200800001E] FX Center for Biomedical Informatics and Information Technology (CBIIT)/Cancer Biomedical Informatics Grid (caBIG) ISRCE yellow task #09-260 to NCI-Frederick and National Cancer Institute/National Institutes of Health contract HHSN261200800001E (to A. B.). Funding for open access charge: National Cancer Institute/National Institutes of Health contract HHSN261200800001E. NR 57 TC 30 Z9 30 U1 1 U2 12 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0305-1048 J9 NUCLEIC ACIDS RES JI Nucleic Acids Res. PD JAN PY 2011 VL 39 SU 1 BP D383 EP D391 DI 10.1093/nar/gkq1170 PG 9 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 701PA UT WOS:000285831700064 PM 21097885 ER PT J AU Fingerman, IM McDaniel, L Zhang, XA Ratzat, W Hassan, T Jiang, ZF Cohen, RF Schuler, GD AF Fingerman, Ian M. McDaniel, Lee Zhang, Xuan Ratzat, Walter Hassan, Tarek Jiang, Zhifang Cohen, Robert F. Schuler, Gregory D. TI NCBI Epigenomics: a new public resource for exploring epigenomic data sets SO NUCLEIC ACIDS RESEARCH LA English DT Article ID EPIGENETIC INHERITANCE; CANCER; CHROMATIN; GENOME AB The Epigenomics database at the National Center for Biotechnology Information (NCBI) is a new resource that has been created to serve as a comprehensive public resource for whole-genome epigenetic data sets Epigenetics is the study of stable and heritable changes in gene expression that occur independently of the primary DNA sequence. Epigenetic mechanisms include post-translational modifications of histones, DNA methylation, chromatin conformation and non-coding RNAs. It has been observed that misregulation of epigenetic processes has been associated with human disease. We have constructed the new resource by selecting the subset of epigenetics-specific data from general-purpose archives, such as the Gene Expression Omnibus, and Sequence Read Archives, and then subjecting them to further review, annotation and reorganization. Raw data is processed and mapped to genomic coordinates to generate 'tracks' that are a visual representation of the data. These data tracks can be viewed using popular genome browsers or downloaded for local analysis. The Epigenomics resource also provides the user with a unique interface that allows for intuitive browsing and searching of data sets based on biological attributes. Currently, there are 69 studies, 337 samples and over 1100 data tracks from five well-studied species that are viewable and downloadable in Epigenomics. C1 [Fingerman, Ian M.; McDaniel, Lee; Zhang, Xuan; Ratzat, Walter; Hassan, Tarek; Jiang, Zhifang; Cohen, Robert F.; Schuler, Gregory D.] NIH, Natl Ctr Biotechnol Informat, Natl Lib Med, Bethesda, MD 20892 USA. RP Schuler, GD (reprint author), NIH, Natl Ctr Biotechnol Informat, Natl Lib Med, 45 Ctr Dr, Bethesda, MD 20892 USA. EM schuler@ncbi.nlm.nih.gov FU National Institutes of Health, National Library of Medicine FX Funding for open access charge: The Intramural Research Program of the National Institutes of Health, National Library of Medicine. NR 18 TC 30 Z9 30 U1 0 U2 2 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0305-1048 EI 1362-4962 J9 NUCLEIC ACIDS RES JI Nucleic Acids Res. PD JAN PY 2011 VL 39 SU 1 BP D908 EP D912 DI 10.1093/nar/gkq1146 PG 5 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 701PA UT WOS:000285831700142 PM 21075792 ER PT J AU Galperin, MY Cochrane, GR AF Galperin, Michael Y. Cochrane, Guy R. TI The 2011 Nucleic Acids Research Database Issue and the online Molecular Biology Database Collection SO NUCLEIC ACIDS RESEARCH LA English DT Article ID RNA MODIFICATION DATABASE; PROTEIN DATA-BANK; COMPREHENSIVE DATABASE; UPDATE; CANCER; GENES; INFORMATION; KNOWLEDGE; SEQUENCE AB The current 18th Database Issue of Nucleic Acids Research features descriptions of 96 new and 83 updated online databases covering various areas of molecular biology. It includes two editorials, one that discusses COMBREX, a new exciting project aimed at figuring out the functions of the 'conserved hypothetical' proteins, and one concerning BioDBcore, a proposed description of the 'minimal information about a biological database'. Papers from the members of the International Nucleotide Sequence Database collaboration (INSDC) describe each of the participating databases, DDBJ, ENA and GenBank, principles of data exchange within the collaboration, and the recently established Sequence Read Archive. A testament to the longevity of databases, this issue includes updates on the RNA modification database, Definition of Secondary Structure of Proteins (DSSP) and Homology-derived Secondary Structure of Proteins (HSSP) databases, which have not been featured here in > 12 years. There is also a block of papers describing recent progress in protein structure databases, such as Protein DataBank (PDB), PDB in Europe (PDBe), CATH, SUPERFAMILY and others, as well as databases on protein structure modeling, protein-protein interactions and the organization of inter-protein contact sites. Other highlights include updates of the popular gene expression databases, GEO and ArrayExpress, several cancer gene databases and a detailed description of the UK PubMed Central project. The Nucleic Acids Research online Database Collection, available at: http://www.oxfordjournals.org/nar/database/a, now lists 1330 carefully selected molecular biology databases. The full content of the Database Issue is freely available online at the Nucleic Acids Research web site http://nar.oxfordjournals.org/). C1 [Galperin, Michael Y.] Natl Lib Med, Natl Ctr Biotechnol Informat, NIH, Bethesda, MD 20894 USA. [Cochrane, Guy R.] EMBL European Bioinformat Inst, Cambridge CB10 1SD, England. RP Galperin, MY (reprint author), Natl Lib Med, Natl Ctr Biotechnol Informat, NIH, Bethesda, MD 20894 USA. EM galperin@ncbi.nlm.nih.gov RI Galperin, Michael/B-5859-2013; OI Galperin, Michael/0000-0002-2265-5572; Cochrane, Guy/0000-0001-7954-7057 FU US National Institutes of Health; European Molecular Biology Laboratory; Oxford University Press FX Intramural Research Program of the US National Institutes of Health (to M.Y.G.); European Molecular Biology Laboratory (to G. R. C.). Funding for open access charge: Waived by Oxford University Press. NR 61 TC 40 Z9 40 U1 0 U2 7 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0305-1048 J9 NUCLEIC ACIDS RES JI Nucleic Acids Res. PD JAN PY 2011 VL 39 SU 1 BP D1 EP D6 DI 10.1093/nar/gkq1243 PG 6 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 701PA UT WOS:000285831700001 PM 21177655 ER PT J AU Gaudet, P Bairoch, A Field, D Sansone, SA Taylor, C Attwood, TK Bateman, A Blake, JA Bult, CJ Cherry, JM Chisholm, RL Cochrane, G Cook, CE Eppig, JT Galperin, MY Gentleman, R Goble, CA Gojobori, T Hancock, JM Howe, DG Imanishi, T Kelso, J Landsman, D Lewis, SE Karsch-Mizrachi, I Orchard, S Ouellette, BFF Ranganathan, S Richardson, L Rocca-Serra, P Schofield, PN Smedley, D Southan, C Tan, TW Tatusova, T Whetzel, PL White, O Yamasaki, C AF Gaudet, Pascale Bairoch, Amos Field, Dawn Sansone, Susanna-Assunta Taylor, Chris Attwood, Teresa K. Bateman, Alex Blake, Judith A. Bult, Carol J. Cherry, J. Michael Chisholm, Rex L. Cochrane, Guy Cook, Charles E. Eppig, Janan T. Galperin, Michael Y. Gentleman, Robert Goble, Carole A. Gojobori, Takashi Hancock, John M. Howe, Douglas G. Imanishi, Tadashi Kelso, Janet Landsman, David Lewis, Suzanna E. Karsch-Mizrachi, Ilene Orchard, Sandra Ouellette, B. F. Francis Ranganathan, Shoba Richardson, Lorna Rocca-Serra, Philippe Schofield, Paul N. Smedley, Damian Southan, Christopher Tan, Tin Wee Tatusova, Tatiana Whetzel, Patricia L. White, Owen Yamasaki, Chisato CA BioDBCore Working Grp TI Towards BioDBcore: a community-defined information specification for biological databases SO NUCLEIC ACIDS RESEARCH LA English DT Article ID BIOINFORMATICS; RESOURCES AB The present article proposes the adoption of a community-defined, uniform, generic description of the core attributes of biological databases, BioDBCore. The goals of these attributes are to provide a general overview of the database landscape, to encourage consistency and interoperability between resources and to promote the use of semantic and syntactic standards. BioDBCore will make it easier for users to evaluate the scope and relevance of available resources. This new resource will increase the collective impact of the information present in biological databases. C1 [Gaudet, Pascale; Bairoch, Amos] CMU, Swiss Inst Bioinformat, CH-1211 Geneva 4, Switzerland. [Gaudet, Pascale; Chisholm, Rex L.] Northwestern Univ, Feinberg Sch Med, Chicago, IL 60611 USA. [Field, Dawn] NERC, Ctr Ecol & Hydrol, Oxford OX1 3SR, England. [Sansone, Susanna-Assunta; Cook, Charles E.; Rocca-Serra, Philippe] Univ Oxford, Oxford E Res Ctr, Oxford OX1 3QG, England. [Taylor, Chris; Cochrane, Guy; Orchard, Sandra; Smedley, Damian] European Bioinformat Inst, European Mol Biol Lab EMBL Outstn, Cambridge CB10 1SD, England. [Attwood, Teresa K.] Univ Manchester, Fac Life Sci, Manchester M13 9PT, Lancs, England. [Attwood, Teresa K.; Goble, Carole A.] Univ Manchester, Sch Comp Sci, Manchester M13 9PT, Lancs, England. [Bateman, Alex] Wellcome Trust Sanger Inst, Cambridge CB10 1SA, England. [Blake, Judith A.; Bult, Carol J.; Eppig, Janan T.] Jackson Lab, Bar Harbor, ME 04609 USA. [Cherry, J. Michael] Stanford Univ, Dept Genet, Stanford, CA 94305 USA. [Galperin, Michael Y.; Karsch-Mizrachi, Ilene; Tatusova, Tatiana] Natl Lib Med, Natl Ctr Biotechnol Informat, NIH, Bethesda, MD 20894 USA. [Gentleman, Robert] Genentech Inc, San Francisco, CA 94080 USA. [Gentleman, Robert; Kelso, Janet; Landsman, David; Ouellette, B. F. Francis] Oxford Univ Press, DATABASE, Journal Biol Databases & Curat, Oxford OX2 6DP, England. [Gojobori, Takashi; Imanishi, Tadashi; Yamasaki, Chisato] Natl Inst Adv Ind Sci & Technol, Biomed Informat Res Ctr, Koto Ku, Tokyo 1350064, Japan. [Gojobori, Takashi] Natl Inst Genet, Ctr Informat Biol, Mishima, Shizuoka 4118540, Japan. [Gojobori, Takashi] Natl Inst Genet, DNA Data Bank Japan, Mishima, Shizuoka 4118540, Japan. [Hancock, John M.] MRC Harwell, Mammalian Genet Unit, Didcot OX11 0RD, Oxon, England. [Howe, Douglas G.] 5291 Univ Oregon, Zebrafish Model Organism Database, Eugene, OR 97401 USA. [Kelso, Janet] Max Planck Inst Evolutionary Anthropol, Dept Evolutionary Genet, Leipzig, Germany. [Lewis, Suzanna E.] Univ Calif Berkeley, Lawrence Berkeley Lab, Genom Div, Berkeley, CA 94720 USA. [Ouellette, B. F. Francis] Ontario Inst Canc Res, Toronto, ON M5G 0A3, Canada. [Ranganathan, Shoba] Macquarie Univ, Dept Chem & Biomol Sci, Sydney, NSW 2109, Australia. [Ranganathan, Shoba; Tan, Tin Wee] Natl Univ Singapore, Dept Biochem, Yong Loo Lin Sch Med, Singapore 117548, Singapore. [Richardson, Lorna] Western Gen Hosp, MRC Human Genet Unit, Inst Genet & Mol Med, Edinburgh EH4 2XU, Midlothian, Scotland. [Schofield, Paul N.] Univ Cambridge, Dept Physiol Dev & Neurosci, Cambridge CB2 3EG, England. [Southan, Christopher] ChrisDS Consulting, Gothenburg, Sweden. [Whetzel, Patricia L.] Stanford Univ, Stanford Ctr Biomed Informat Res, Natl Ctr Biomed Ontol, Stanford, CA 94305 USA. [White, Owen] Univ Maryland, Inst Genome Sci, Sch Med, Baltimore, MD 21201 USA. RP Gaudet, P (reprint author), CMU, Swiss Inst Bioinformat, 1 Rue Michel Servet, CH-1211 Geneva 4, Switzerland. EM pascale.gaudet@isb-sib.ch RI Field, Dawn/C-1653-2010; Bateman, Alex/E-6518-2011; Hancock, John/A-2442-2009; Galperin, Michael/B-5859-2013; Tan, Tin Wee/B-8963-2009; OI Bairoch, Amos/0000-0003-2826-6444; Landsman, David/0000-0002-9819-6675; Orchard, Sandra/0000-0002-8878-3972; Blake, Judith/0000-0001-8522-334X; Southan, Christopher/0000-0001-9580-0446; Hancock, John/0000-0003-2991-2217; Galperin, Michael/0000-0002-2265-5572; Tan, Tin Wee/0000-0002-4062-2854; Cherry, J. Michael/0000-0001-9163-5180; Ranganathan, Shoba/0000-0002-8290-813X; Bateman, Alex/0000-0002-6982-4660; Lewis, Suzanna/0000-0002-8343-612X; Goble, Carole/0000-0003-1219-2137; Richardson, Lorna/0000-0002-3655-5660; Cochrane, Guy/0000-0001-7954-7057 FU Biotechnology and Biological Sciences Research Council [BB/E025080/1, BB/F01046X/1, BB/I000771/1]; Intramural NIH HHS [Z99 LM999999]; Medical Research Council [MC_U127527203, MC_U142684171]; NHGRI NIH HHS [U41 HG000330]; NIGMS NIH HHS [R01 GM087371, R01 GM064426, R01 GM064426-10, R01 GM087371-03] NR 12 TC 23 Z9 23 U1 1 U2 4 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0305-1048 EI 1362-4962 J9 NUCLEIC ACIDS RES JI Nucleic Acids Res. PD JAN PY 2011 VL 39 SU 1 BP D7 EP D10 DI 10.1093/nar/gkq1173 PG 4 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 701PA UT WOS:000285831700002 PM 21097465 ER PT J AU Leinonen, R Sugawara, H Shumway, M AF Leinonen, Rasko Sugawara, Hideaki Shumway, Martin CA Int Nucleotide Sequence Database C TI The Sequence Read Archive SO NUCLEIC ACIDS RESEARCH LA English DT Article AB The combination of significantly lower cost and increased speed of sequencing has resulted in an explosive growth of data submitted into the primary next-generation sequence data archive, the Sequence Read Archive (SRA). The preservation of experimental data is an important part of the scientific record, and increasing numbers of journals and funding agencies require that next-generation sequence data are deposited into the SRA. The SRA was established as a public repository for the next-generation sequence data and is operated by the International Nucleotide Sequence Database Collaboration (INSDC). INSDC partners include the National Center for Biotechnology Information (NCBI), the European Bioinformatics Institute (EBI) and the DNA Data Bank of Japan (DDBJ). The SRA is accessible at http://www.ncbi.nlm.nih.gov/Traces/sra from NCBI, at http://www.ebi.ac.uk/ena from EBI and at http://trace.ddbj.nig.ac.jp from DDBJ. In this article, we present the content and structure of the SRA, detail our support for sequencing platforms and provide recommended data submission levels and formats. We also briefly outline our response to the challenge of data growth. C1 [Leinonen, Rasko] European Bioinformat Inst, Cambridge CB10 1SD, England. [Sugawara, Hideaki] Res Org Informat & Syst, Ctr Informat Biol, Mishima, Shizuoka 4118540, Japan. [Sugawara, Hideaki] Res Org Informat & Syst, DNA Data Bank Japan, Natl Inst Genet, Mishima, Shizuoka 4118540, Japan. [Shumway, Martin] Natl Lib Med, Natl Ctr Biotechnol Informat, NIH, Bethesda, MD 20894 USA. RP Leinonen, R (reprint author), European Bioinformat Inst, Wellcome Trust Genome Campus, Cambridge CB10 1SD, England. EM rasko@ebi.ac.uk OI Cochrane, Guy/0000-0001-7954-7057; Leinonen, Rasko/0000-0002-2639-7187 FU European Molecular Biology Laboratory; European Commission; Wellcome Trust; Ministry of Education, Culture, Sports, Science and Technology of Japan; NIH, National Library of Medicine FX European Molecular Biology Laboratory, European Commission and the Wellcome Trust; Ministry of Education, Culture, Sports, Science and Technology of Japan (to D.D.B.J.'s work on SRA and Trace Archive); Intramural Research Program of the NIH, National Library of Medicine (to NCBI's SRA work). Funding for open access charge: European Molecular Biology Laboratory. NR 9 TC 208 Z9 210 U1 3 U2 25 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0305-1048 J9 NUCLEIC ACIDS RES JI Nucleic Acids Res. PD JAN PY 2011 VL 39 SU 1 BP D19 EP D21 DI 10.1093/nar/gkq1019 PG 3 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 701PA UT WOS:000285831700005 PM 21062823 ER PT J AU Maglott, D Ostell, J Pruitt, KD Tatusova, T AF Maglott, Donna Ostell, Jim Pruitt, Kim D. Tatusova, Tatiana TI Entrez Gene: gene-centered information at NCBI SO NUCLEIC ACIDS RESEARCH LA English DT Article AB Entrez Gene (http://www.ncbi.nlm.nih.gov/gene) is National Center for Biotechnology Information (NCBI)'s database for gene-specific information. Entrez Gene maintains records from genomes which have been completely sequenced, which have an active research community to submit gene-specific information, or which are scheduled for intense sequence analysis. The content represents the integration of curation and automated processing from NCBI's Reference Sequence project (RefSeq), collaborating model organism databases, consortia such as Gene Ontology and other databases within NCBI. Records in Entrez Gene are assigned unique, stable and tracked integers as identifiers. The content (nomenclature, genomic location, gene products and their attributes, markers, phenotypes and links to citations, sequences, variation details, maps, expression, homologs, protein domains and external databases) is available via interactive browsing through NCBI's Entrez system, via NCBI's Entrez programming utilities (E-Utilities) and for bulk transfer by FTP. C1 [Maglott, Donna; Ostell, Jim; Pruitt, Kim D.; Tatusova, Tatiana] Natl Lib Med, Natl Ctr Biotechnol Informat, NIH, Rockville, MD 20852 USA. RP Maglott, D (reprint author), Natl Lib Med, Natl Ctr Biotechnol Informat, NIH, Rockville, MD 20852 USA. EM maglott@ncbi.nlm.nih.gov FU National Institutes of Health; National Library of Medicine FX Funding for open access charge: The Intramural Research Program of the National Institutes of Health; National Library of Medicine. NR 9 TC 290 Z9 295 U1 0 U2 21 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0305-1048 J9 NUCLEIC ACIDS RES JI Nucleic Acids Res. PD JAN PY 2011 VL 39 SU 1 BP D52 EP D57 DI 10.1093/nar/gkq1237 PG 6 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 701PA UT WOS:000285831700010 PM 21115458 ER PT J AU Marchler-Bauer, A Lu, SN Anderson, JB Chitsaz, F Derbyshire, MK DeWeese-Scott, C Fong, JH Geer, LY Geer, RC Gonzales, NR Gwadz, M Hurwitz, DI Jackson, JD Ke, ZX Lanczycki, CJ Lu, F Marchler, GH Mullokandov, M Omelchenko, MV Robertson, CL Song, JS Thanki, N Yamashita, RA Zhang, DC Zhang, NG Zheng, CJ Bryant, SH AF Marchler-Bauer, Aron Lu, Shennan Anderson, John B. Chitsaz, Farideh Derbyshire, Myra K. DeWeese-Scott, Carol Fong, Jessica H. Geer, Lewis Y. Geer, Renata C. Gonzales, Noreen R. Gwadz, Marc Hurwitz, David I. Jackson, John D. Ke, Zhaoxi Lanczycki, Christopher J. Lu, Fu Marchler, Gabriele H. Mullokandov, Mikhail Omelchenko, Marina V. Robertson, Cynthia L. Song, James S. Thanki, Narmada Yamashita, Roxanne A. Zhang, Dachuan Zhang, Naigong Zheng, Chanjuan Bryant, Stephen H. TI CDD: a Conserved Domain Database for the functional annotation of proteins SO NUCLEIC ACIDS RESEARCH LA English DT Article ID GENOMES; SEARCH AB NCBI's Conserved Domain Database (CDD) is a resource for the annotation of protein sequences with the location of conserved domain footprints, and functional sites inferred from these footprints. CDD includes manually curated domain models that make use of protein 3D structure to refine domain models and provide insights into sequence/structure/function relationships. Manually curated models are organized hierarchically if they describe domain families that are clearly related by common descent. As CDD also imports domain family models from a variety of external sources, it is a partially redundant collection. To simplify protein annotation, redundant models and models describing homologous families are clustered into superfamilies. By default, domain footprints are annotated with the corresponding superfamily designation, on top of which specific annotation may indicate high-confidence assignment of family membership. Pre-computed domain annotation is available for proteins in the Entrez/Protein dataset, and a novel interface, Batch CD-Search, allows the computation and download of annotation for large sets of protein queries. CDD can be accessed via http://www.ncbi.nlm.nih.gov/Structure/cdd/cdd.shtml. C1 [Marchler-Bauer, Aron; Lu, Shennan; Anderson, John B.; Chitsaz, Farideh; Derbyshire, Myra K.; DeWeese-Scott, Carol; Fong, Jessica H.; Geer, Lewis Y.; Geer, Renata C.; Gonzales, Noreen R.; Gwadz, Marc; Hurwitz, David I.; Jackson, John D.; Ke, Zhaoxi; Lanczycki, Christopher J.; Lu, Fu; Marchler, Gabriele H.; Mullokandov, Mikhail; Omelchenko, Marina V.; Robertson, Cynthia L.; Song, James S.; Thanki, Narmada; Yamashita, Roxanne A.; Zhang, Dachuan; Zhang, Naigong; Zheng, Chanjuan; Bryant, Stephen H.] NIH, Natl Ctr Biotechnol Informat, Natl Lib Med, Bethesda, MD 20894 USA. RP Marchler-Bauer, A (reprint author), NIH, Natl Ctr Biotechnol Informat, Natl Lib Med, Bldg 38 A,Room 8N805,8600 Rockville Pike, Bethesda, MD 20894 USA. EM bauer@ncbi.nlm.nih.gov RI Sincan, Murat /A-3794-2010; Geer, Lewis/H-2714-2014; OI Marchler-Bauer, Aron/0000-0003-1516-0712 FU National Library of Medicine at the National Institutes of Health/DHHS FX Funding for open access charge: Intramural Research Program of the National Library of Medicine at the National Institutes of Health/DHHS. NR 10 TC 1280 Z9 1312 U1 12 U2 124 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0305-1048 J9 NUCLEIC ACIDS RES JI Nucleic Acids Res. PD JAN PY 2011 VL 39 SU 1 BP D225 EP D229 DI 10.1093/nar/gkq1189 PG 5 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 701PA UT WOS:000285831700038 PM 21109532 ER PT J AU Sayers, EW Barrett, T Benson, DA Bolton, E Bryant, SH Canese, K Chetvernin, V Church, DM DiCuccio, M Federhen, S Feolo, M Fingerman, IM Geer, LY Helmberg, W Kapustin, Y Landsman, D Lipman, DJ Lu, ZY Madden, TL Madej, T Maglott, DR Marchler-Bauer, A Miller, V Mizrachi, I Ostell, J Panchenko, A Phan, L Pruitt, KD Schuler, GD Sequeira, E Sherry, ST Shumway, M Sirotkin, K Slotta, D Souvorov, A Starchenko, G Tatusova, TA Wagner, L Wang, YL Wilbur, WJ Yaschenko, E Ye, JA AF Sayers, Eric W. Barrett, Tanya Benson, Dennis A. Bolton, Evan Bryant, Stephen H. Canese, Kathi Chetvernin, Vyacheslav Church, Deanna M. DiCuccio, Michael Federhen, Scott Feolo, Michael Fingerman, Ian M. Geer, Lewis Y. Helmberg, Wolfgang Kapustin, Yuri Landsman, David Lipman, David J. Lu, Zhiyong Madden, Thomas L. Madej, Tom Maglott, Donna R. Marchler-Bauer, Aron Miller, Vadim Mizrachi, Ilene Ostell, James Panchenko, Anna Phan, Lon Pruitt, Kim D. Schuler, Gregory D. Sequeira, Edwin Sherry, Stephen T. Shumway, Martin Sirotkin, Karl Slotta, Douglas Souvorov, Alexandre Starchenko, Grigory Tatusova, Tatiana A. Wagner, Lukas Wang, Yanli Wilbur, W. John Yaschenko, Eugene Ye, Jian TI Database resources of the National Center for Biotechnology Information SO NUCLEIC ACIDS RESEARCH LA English DT Article ID ONLINE MENDELIAN INHERITANCE; PROTEIN SEQUENCES; NCBI; SEARCH; ENTREZ; GENE; GENOMES; SYSTEM; KEGG; TOOL AB In addition to maintaining the GenBank (R) nucleic acid sequence database, the National Center for Biotechnology Information (NCBI) provides analysis and retrieval resources for the data in GenBank and other biological data made available through the NCBI Web site. NCBI resources include Entrez, the Entrez Programming Utilities, MyNCBI, PubMed, PubMed Central (PMC), Entrez Gene, the NCBI Taxonomy Browser, BLAST, BLAST Link (BLink), Primer-BLAST, COBALT, Electronic PCR, OrfFinder, Splign, ProSplign, RefSeq, UniGene, HomoloGene, ProtEST, dbMHC, dbSNP, dbVar, Epigenomics, Cancer Chromosomes, Entrez Genomes and related tools, the Map Viewer, Model Maker, Evidence Viewer, Trace Archive, Sequence Read Archive, Retroviral Genotyping Tools, HIV-1/Human Protein Interaction Database, Gene Expression Omnibus (GEO), Entrez Probe, GENSAT, Online Mendelian Inheritance in Man (OMIM), Online Mendelian Inheritance in Animals (OMIA), the Molecular Modeling Database (MMDB), the Conserved Domain Database (CDD), the Conserved Domain Architecture Retrieval Tool (CDART), IBIS, Biosystems, Peptidome, OMSSA, Protein Clusters and the PubChem suite of small molecule databases. Augmenting many of the Web applications are custom implementations of the BLAST program optimized to search specialized data sets. All of these resources can be accessed through the NCBI home page at www.ncbi.nlm.nih.gov. C1 [Sayers, Eric W.; Barrett, Tanya; Benson, Dennis A.; Bolton, Evan; Bryant, Stephen H.; Canese, Kathi; Chetvernin, Vyacheslav; Church, Deanna M.; DiCuccio, Michael; Federhen, Scott; Feolo, Michael; Fingerman, Ian M.; Geer, Lewis Y.; Kapustin, Yuri; Landsman, David; Lipman, David J.; Lu, Zhiyong; Madden, Thomas L.; Madej, Tom; Maglott, Donna R.; Marchler-Bauer, Aron; Miller, Vadim; Mizrachi, Ilene; Ostell, James; Panchenko, Anna; Phan, Lon; Pruitt, Kim D.; Schuler, Gregory D.; Sequeira, Edwin; Sherry, Stephen T.; Shumway, Martin; Sirotkin, Karl; Slotta, Douglas; Souvorov, Alexandre; Starchenko, Grigory; Tatusova, Tatiana A.; Wagner, Lukas; Wang, Yanli; Wilbur, W. John; Yaschenko, Eugene; Ye, Jian] Natl Lib Med, Natl Ctr Biotechnol Informat, NIH, Bethesda, MD 20894 USA. [Helmberg, Wolfgang] Med Univ Graz, Univ Clin Blood Grp Serol & Transfus Med, A-8036 Graz, Austria. RP Sayers, EW (reprint author), Natl Lib Med, Natl Ctr Biotechnol Informat, NIH, Bldg 38A,8600 Rockville Pike, Bethesda, MD 20894 USA. EM sayers@ncbi.nlm.nih.gov RI Geer, Lewis/H-2714-2014; OI Marchler-Bauer, Aron/0000-0003-1516-0712; Landsman, David/0000-0002-9819-6675 FU National Institutes of Health, National Library of Medicine FX Funding for open access charge: the Intramural Research Program of the National Institutes of Health, National Library of Medicine. NR 65 TC 316 Z9 325 U1 2 U2 39 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0305-1048 J9 NUCLEIC ACIDS RES JI Nucleic Acids Res. PD JAN PY 2011 VL 39 SU 1 BP D38 EP D51 DI 10.1093/nar/gkq1172 PG 14 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 701PA UT WOS:000285831700009 PM 21097890 ER PT J AU Yellaboina, S Tasneem, A Zaykin, DV Raghavachari, B Jothi, R AF Yellaboina, Sailu Tasneem, Asba Zaykin, Dmitri V. Raghavachari, Balaji Jothi, Raja TI DOMINE: a comprehensive collection of known and predicted domain-domain interactions SO NUCLEIC ACIDS RESEARCH LA English DT Article ID PROTEIN-PROTEIN INTERACTIONS AB DOMINE is a comprehensive collection of known and predicted domain-domain interactions (DDIs) compiled from 15 different sources. The updated DOMINE includes 2285 new domain-domain interactions (DDIs) inferred from experimentally characterized high-resolution three-dimensional structures, and about 3500 novel predictions by five computational approaches published over the last 3 years. These additions bring the total number of unique DDIs in the updated version to 26 219 among 5140 unique Pfam domains, a 23% increase compared to 20 513 unique DDIs among 4346 unique domains in the previous version. The updated version now contains 6634 known DDIs, and features a new classification scheme to assign confidence levels to predicted DDIs. DOMINE will serve as a valuable resource to those studying protein and domain interactions. Most importantly, DOMINE will not only serve as an excellent reference to bench scientists testing for new interactions but also to bioinformaticans seeking to predict novel protein-protein interactions based on the DDIs. The contents of the DOMINE are available at http://domine.utdallas.edu. C1 [Yellaboina, Sailu; Zaykin, Dmitri V.; Jothi, Raja] NIEHS, Biostat Branch, NIH, Res Triangle Pk, NC 27709 USA. [Tasneem, Asba] Duke Univ, Duke Clin Res Inst, Durham, NC 27705 USA. [Raghavachari, Balaji] Univ Texas Dallas, Dept Comp Sci, Richardson, TX 75083 USA. RP Jothi, R (reprint author), NIEHS, Biostat Branch, NIH, POB 12233, Res Triangle Pk, NC 27709 USA. EM jothi@mail.nih.gov RI Jothi, Raja/G-3780-2015 FU National Institute of Environmental Health Sciences, National Institute of Health [Z01ES102625-02] FX This work was supported by the Intramural Research Program of the National Institute of Environmental Health Sciences, National Institute of Health (Project number Z01ES102625-02 to R.J.). NR 23 TC 83 Z9 83 U1 1 U2 7 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0305-1048 J9 NUCLEIC ACIDS RES JI Nucleic Acids Res. PD JAN PY 2011 VL 39 SU 1 BP D730 EP D735 DI 10.1093/nar/gkq1229 PG 6 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 701PA UT WOS:000285831700116 PM 21113022 ER PT J AU Dorjsuren, D Kim, D Maloney, DJ Wilson, DM Simeonov, A AF Dorjsuren, Dorjbal Kim, Daemyung Maloney, David J. Wilson, David M., III Simeonov, Anton TI Complementary non-radioactive assays for investigation of human flap endonuclease 1 activity SO NUCLEIC ACIDS RESEARCH LA English DT Article ID GENE-EXPRESSION; DNA-REPAIR; PROSTATE-CANCER; AURINTRICARBOXYLIC ACID; METHYLATING AGENTS; FEN-1; INHIBITORS; CELLS; IDENTIFICATION; REPLICATION AB FEN1, a key participant in DNA replication and repair, is the major human flap endonuclease that recognizes and cleaves flap DNA structures. Deficiencies in FEN1 function or deletion of the fen1 gene have profound biological effects, including the suppression of repair of DNA damage incurred from the action of various genotoxic agents. Given the importance of FEN1 in resolving abnormal DNA structures, inhibitors of the enzyme carry a potential as enhancers of DNA-interactive anticancer drugs. To facilitate the studies of FEN1 activity and the search for novel inhibitors, we developed a pair of complementary-readout homogeneous assays utilizing fluorogenic donor/quencher and AlphaScreen chemiluminescence strategies. A previously reported FEN1 inhibitor 3-hydroxy-5-methyl-1-phenylthieno[2,3-d]pyrimidine-2,4(1H,3H)-dione displayed equal potency in the new assays, in agreement with its published IC(50). The assays were optimized to a low 4 mu l volume and used to investigate a set of small molecules, leading to the identification of previously-unreported FEN1 inhibitors, among which aurintricarboxylic acid and NSC-13755 (an arylstibonic derivative) displayed submicromolar potency (average IC(50) of 0.59 and 0.93 mu M, respectively). The availability of these simple complementary assays obviates the need for undesirable radiotracer-based assays and should facilitate efforts to develop novel inhibitors for this key biological target. C1 [Dorjsuren, Dorjbal; Maloney, David J.; Simeonov, Anton] NHGRI, NIH Chem Genom Ctr, NIH, Bethesda, MD 20892 USA. [Kim, Daemyung] Cheongju Univ, Dept Genet Engn, Cheongju 360764, South Korea. [Wilson, David M., III] NIA, Lab Mol Gerontol, NIH, Baltimore, MD 21224 USA. RP Simeonov, A (reprint author), NHGRI, NIH Chem Genom Ctr, NIH, Bethesda, MD 20892 USA. EM asimeono@mail.nih.gov FU Molecular Libraries Initiative of the National Institutes of Health Roadmap for Medical Research [1 R03 MH092154-01, U54MH084681]; National Institute on Aging; National Human Genome Research Institute, National Institutes of Health; National Institutes of Health FX Molecular Libraries Initiative of the National Institutes of Health Roadmap for Medical Research [grants 1 R03 MH092154-01 (D.M.W.III) and U54MH084681 (to A. S.)]; Intramural Research Programs of National Institute on Aging and National Human Genome Research Institute, National Institutes of Health. Funding for open access charge: National Institutes of Health Intramural funding. NR 53 TC 17 Z9 18 U1 0 U2 5 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0305-1048 J9 NUCLEIC ACIDS RES JI Nucleic Acids Res. PD JAN PY 2011 VL 39 IS 2 AR e11 DI 10.1093/nar/gkq1082 PG 11 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 712OE UT WOS:000286675300006 PM 21062821 ER PT J AU Cunnane, S Nugent, S Roy, M Courchesne-Loyer, A Croteau, E Tremblay, S Castellano, A Pifferi, F Bocti, C Paquet, N Begdouri, H Bentourkia, M Turcotte, E Allard, M Barberger-Gateau, P Fulop, T Rapoport, SI AF Cunnane, Stephen Nugent, Scott Roy, Maggie Courchesne-Loyer, Alexandre Croteau, Etienne Tremblay, Sebastien Castellano, Alex Pifferi, Fabien Bocti, Christian Paquet, Nancy Begdouri, Hadi Bentourkia, M'hamed Turcotte, Eric Allard, Michele Barberger-Gateau, Pascale Fulop, Tamas Rapoport, Stanley I. TI Brain fuel metabolism, aging, and Alzheimer's disease SO NUTRITION LA English DT Review DE Glucose; Ketones; Brain; Aging; Alzheimer's disease; PET; Insulin; Cognition; Mitochondria ID POSITRON-EMISSION-TOMOGRAPHY; MILD COGNITIVE IMPAIRMENT; CEREBRAL-BLOOD-FLOW; POLYUNSATURATED FATTY-ACIDS; KETONE-BODY METABOLISM; ALTERED GLUCOSE-METABOLISM; CENTRAL-NERVOUS-SYSTEM; SHORT-TERM STARVATION; FDG LUMPED CONSTANT; INSULIN-RESISTANCE AB Lower brain glucose metabolism is present before the onset of clinically measurable cognitive decline in two groups of people at risk of Alzheimer's disease-carriers of apolipoprotein E4, and in those with a maternal family history of AD. Supported by emerging evidence from in vitro and animal studies, these reports suggest that brain hypometabolism may precede and therefore contribute to the neuropathologic cascade leading to cognitive decline in AD. The reason brain hypometabolism develops is unclear but may include defects in brain glucose transport, disrupted glycolysis, and/or impaired mitochondrial function. Methodologic issues presently preclude knowing with certainty whether or not aging in the absence of cognitive impairment is necessarily associated with lower brain glucose metabolism. Nevertheless, aging appears to increase the risk of deteriorating systemic control of glucose utilization, which, in turn, may increase the risk of declining brain glucose uptake, at least in some brain regions. A contributing role of deteriorating glucose availability to or metabolism by the brain in AD does not exclude the opposite effect, i.e., that neurodegenerative processes in AD further decrease brain glucose metabolism because of reduced synaptic functionality and hence reduced energy needs, thereby completing a vicious cycle. Strategies to reduce the risk of AD by breaking this cycle should aim to (1) improve insulin sensitivity by improving systemic glucose utilization, or (2) bypass deteriorating brain glucose metabolism using approaches that safely induce mild, sustainable ketonemia. (C) 2011 Elsevier Inc. All rights reserved. C1 [Cunnane, Stephen; Nugent, Scott; Roy, Maggie; Courchesne-Loyer, Alexandre; Tremblay, Sebastien; Castellano, Alex; Bocti, Christian; Fulop, Tamas] Univ Sherbrooke, Geriatr Inst, Res Ctr Aging, Hlth & Social Serv Ctr, Sherbrooke, PQ J1K 2R1, Canada. [Cunnane, Stephen; Bocti, Christian; Fulop, Tamas] Univ Sherbrooke, Dept Med, Sherbrooke, PQ J1K 2R1, Canada. [Cunnane, Stephen; Nugent, Scott; Roy, Maggie; Courchesne-Loyer, Alexandre] Univ Sherbrooke, Dept Physiol & Biophys, Sherbrooke, PQ J1K 2R1, Canada. [Croteau, Etienne; Tremblay, Sebastien; Paquet, Nancy; Begdouri, Hadi; Bentourkia, M'hamed; Turcotte, Eric] Univ Sherbrooke, Dept Radiobiol & Nucl Med, Sherbrooke, PQ J1K 2R1, Canada. [Barberger-Gateau, Pascale] Univ Victor Segalen Bordeaux 2, F-33076 Bordeaux, France. [Barberger-Gateau, Pascale] INSERM, U897, F-33076 Bordeaux, France. [Rapoport, Stanley I.] NIA, Brain Physiol & Metab Sect, Bethesda, MD 20892 USA. [Pifferi, Fabien] UMR CNRS MNHN 7179, Brunoy, France. [Allard, Michele] Ecole Prat Hautes Etud, F-75013 Paris, France. [Allard, Michele] UMR CNRS 5231, Paris, France. RP Cunnane, S (reprint author), Univ Sherbrooke, Geriatr Inst, Res Ctr Aging, Hlth & Social Serv Ctr, Sherbrooke, PQ J1K 2R1, Canada. EM stephen.cunnane@usherbrooke.ca RI ALLARD, Michele/D-8538-2014 FU Canada Research Chairs secretariat (SCC); CIHR; NSERC; CFI; AFMNet; Universite de Sherbrooke (Faculty of Medicine and Health Sciences and the Department of Medicine); Sherbrooke Molecular Imaging Center; Etienne-Le Bel Clinical Research Centre; Research Center on Aging; FQRNT; Intramural Program of the National Institute on Aging, National Institutes of Health, USA FX The authors declare no conflicts. Financial support for the research described here that was done by our group came from the Canada Research Chairs secretariat (SCC), CIHR, NSERC, CFI, AFMNet, Universite de Sherbrooke (Faculty of Medicine and Health Sciences and the Department of Medicine), the Sherbrooke Molecular Imaging Center, the Etienne-Le Bel Clinical Research Centre, and the Research Center on Aging (both FRSQ funded), and FQRNT (CFQCU program). The contribution of S.I. Rapoport was entirely supported by the Intramural Program of the National Institute on Aging, National Institutes of Health, USA. Excellent assistance was provided by Jennifer Mercier-Tremblay, Melanie Fortier, Julie Desgagne, Conrad Filteau, Chantal Langevin, Dr. Otman Sarrhini, and Esteban O Espinosa. NR 218 TC 150 Z9 153 U1 4 U2 43 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0899-9007 J9 NUTRITION JI Nutrition PD JAN PY 2011 VL 27 IS 1 BP 3 EP 20 DI 10.1016/j.nut.2010.07.021 PG 18 WC Nutrition & Dietetics SC Nutrition & Dietetics GA 699JM UT WOS:000285659700002 PM 21035308 ER PT J AU John, EM Stern, MC Sinha, R Koo, J AF John, Esther M. Stern, Mariana C. Sinha, Rashmi Koo, Jocelyn TI Meat Consumption, Cooking Practices, Meat Mutagens, and Risk of Prostate Cancer SO NUTRITION AND CANCER-AN INTERNATIONAL JOURNAL LA English DT Article ID HETEROCYCLIC AMINE CONTENT; FOOD FREQUENCY QUESTIONNAIRE; MULTIETHNIC COHORT; AFRICAN-AMERICANS; ANIMAL PRODUCTS; VARYING DEGREES; PROCESSED MEAT; UNITED-STATES; COOKED FOODS; DIETARY-FAT AB Consumption of red meat, particularly well-done meat, has been associated with increased prostate cancer risk. High-temperature cooking methods such as grilling and barbecuing may produce heterocyclic amines (HCAs) and polycyclic aromatic hydrocarbons (PAHs), which are known carcinogens. We assessed the association with meat consumption and estimated HCA and PAH exposure in a population-based case-control study of prostate cancer. Newly diagnosed cases aged 40-79 years (531 advanced cases, 195 localized cases) and 527 controls were asked about dietary intake, including usual meat cooking methods and doneness levels. Odds ratios (OR) and 95% confidence intervals (CI) were calculated using multivariate logistic regression. For advanced prostate cancer, but not localized disease, increased risks were associated with higher consumption of hamburgers (OR = 1.79, CI = 1.10-2.92), processed meat (OR = 1.57, CI = 1.04-2.36), grilled red meat (OR = 1.63, CI = 0.99-2.68), and well-done red meat (OR = 1.52, CI = 0.93-2.46), and intermediate intake of 2-amino-1-methyl1-6-phenylimidazo[4,5-b]pyridine (PhIP) (Quartile 2 vs. 1: OR = 1.41, CI = 0.98-2.01; Quartile 3 vs. 1: OR = 1.42, CI = 0.98-2.04), but not for higher intake. White meat consumption was not associated with prostate cancer. These findings provide further evidence that consumption of processed meat and red meat cooked at high temperature is associated with increased risk of advanced, but not localized, prostate cancer. C1 [John, Esther M.; Koo, Jocelyn] Canc Prevent Inst Calif, Fremont, CA 94538 USA. [John, Esther M.] Stanford Univ, Div Epidemiol, Dept Hlth Res & Policy, Sch Med, Stanford, CA 94305 USA. [John, Esther M.] Stanford Canc Ctr, Stanford, CA USA. [Stern, Mariana C.] Univ So Calif, Keck Sch Med, Dept Prevent Med, Kenneth Norris Jr Comprehens Canc Ctr, Los Angeles, CA 90033 USA. [Sinha, Rashmi] NCI, Div Canc Epidemiol & Genet, Rockville, MD USA. RP John, EM (reprint author), Canc Prevent Inst Calif, 2201 Walnut Ave,Suite 300, Fremont, CA 94538 USA. EM es-ther.john@CPIC.org RI Sinha, Rashmi/G-7446-2015 OI Sinha, Rashmi/0000-0002-2466-7462 FU California Cancer Research Program [864A-8702-S3514, 99-00527V-10182]; National Cancer Institute, National Institutes of Health [N01-PC-35136]; California Cancer Registry; Public Health Institute [1006128]; Prostate Cancer Foundation; National Institute of Environmental Health Sciences [5P30 ES07048] FX This research was supported by Grants 864A-8702-S3514 and 99-00527V-10182 (to Esther M. John) from the California Cancer Research Program. Cancer incidence data used in this article have been collected by the Greater Bay Area Cancer Registry of the Cancer Prevention Institute of California (formerly the Northern California Cancer Center), under contract N01-PC-35136 with the National Cancer Institute, National Institutes of Health, and with support of the California Cancer Registry, a project of the Cancer Surveillance Section, California Department of Health Services, under subcontract 1006128 with the Public Health Institute. Mention of trade names, commercial products, specific equipment, or organizations does not constitute endorsement, guarantee, or warranty by the State of California Department of Health Services or the U.S. Government, nor does it imply approval to the exclusion of other products. The views expressed in this article represent those of the authors and do not necessarily reflect the position or policies of the Cancer Prevention Institute of California, the California Public Health Institute, the State of California Department of Health Services, or the U. S. Department of Health and Human Services. Mariana C. Stern received support from the Prostate Cancer Foundation and Grant 5P30 ES07048 from the National Institute of Environmental Health Sciences. NR 54 TC 31 Z9 32 U1 2 U2 21 PU LAWRENCE ERLBAUM ASSOC INC-TAYLOR & FRANCIS PI PHILADELPHIA PA 325 CHESTNUT STREET, STE 800, PHILADELPHIA, PA 19106 USA SN 0163-5581 J9 NUTR CANCER JI Nutr. Cancer PY 2011 VL 63 IS 4 BP 525 EP 537 AR PII 936900387 DI 10.1080/01635581.2011.539311 PG 13 WC Oncology; Nutrition & Dietetics SC Oncology; Nutrition & Dietetics GA 768WT UT WOS:000290970100005 PM 21526454 ER PT S AU Baik, M Yu, JH Hennighausen, L AF Baik, Myunggi Yu, Ji Hoon Hennighausen, Lothar BE Surh, YJ Song, YS Han, JY Jun, TW Na, HK TI Growth hormone-STAT5 regulation of growth, hepatocellular carcinoma, and liver metabolism SO NUTRITION AND PHYSICAL ACTIVITY IN AGING, OBESITY, AND CANCER SE Annals of the New York Academy of Sciences LA English DT Article; Proceedings Paper CT 2nd International Conference on Nutrition and Physical Activity in Aging, Obesity, and Cancer (NAPA 2011) CY FEB 16-19, 2010-2011 CL Gyeongju, SOUTH KOREA DE growth hormone; STAT5; liver function ID I GENE-TRANSCRIPTION; LITHOCHOLIC ACID 6-BETA-HYDROXYLASE; SIGNAL TRANSDUCER; MOUSE-LIVER; MICROARRAY ANALYSIS; CELL-PROLIFERATION; SKELETAL-MUSCLE; EXPRESSION; STAT5B; ACTIVATION AB The liver is a primary target of growth hormone (GH). GH signals arc mediated by the transcription factor signal transducer and activator of transcription 5 (STAT5). Here, we focus on recent discoveries about the role of GH-STAT5 signaling in hepatic physiology and pathophysiology. We discuss roles of the GH-STAT5 axis in body growth, lipid metabolism, and the cell cycle pertaining to hepatosteatosis, fibrosis, and hepatocellular carcinoma. Finally, we discuss recent discoveries about the role of GH-STAT5 in sex-specific gene expression and bile acid, steroid, and drug metabolism. C1 [Yu, Ji Hoon; Hennighausen, Lothar] NIH, Lab Genet & Physiol, Bethesda, MD 20892 USA. [Baik, Myunggi; Hennighausen, Lothar] Chonnam Natl Univ, WCU RNNM, Dept Mol Biotechnol, Kwangju, South Korea. RP Hennighausen, L (reprint author), NIH, Lab Genet & Physiol, Bldg 10, Bethesda, MD 20892 USA. EM lotharh@mail.nih.gov FU NIH; NRF [R33-10059]; Rural Development Administration, Republic of Korea [PJ008191032011] FX This work was funded in part through the Intramural program of the NIH and through a grant from WCU Project (R33-10059) through the NRF and by a grant from the Next-Generation BioGreen 21 Program (No. PJ008191032011), Rural Development Administration, Republic of Korea. NR 54 TC 33 Z9 34 U1 1 U2 6 PU BLACKWELL SCIENCE PUBL PI OXFORD PA OSNEY MEAD, OXFORD OX2 0EL, ENGLAND SN 0077-8923 BN 978-1-57331-842-6 J9 ANN NY ACAD SCI JI Ann.NY Acad.Sci. PY 2011 VL 1229 BP 29 EP 37 DI 10.1111/j.1749-6632.2011.06100.x PG 9 WC Endocrinology & Metabolism; Multidisciplinary Sciences; Nutrition & Dietetics SC Endocrinology & Metabolism; Science & Technology - Other Topics; Nutrition & Dietetics GA BWJ49 UT WOS:000294027800006 PM 21793836 ER PT J AU Boyce, JA Assa'ad, A Burks, AW Jones, SM Sampson, HA Wood, RA Plaut, M Cooper, SF Fenton, MJ Arshad, SH Bahna, SL Beck, LA Byrd-Bredbenner, C Camargo, CA Eichenfield, L Furuta, GT Hanifin, JM Jones, C Kraft, M Levy, BD Lieberman, P Luccioli, S McCall, KM Schneider, LC Simon, RA Simons, FER Teach, SJ Yawn, BP Schwaninger, JM AF Boyce, Joshua A. Assa'ad, Amal Burks, A. Wesley Jones, Stacie M. Sampson, Hugh A. Wood, Robert A. Plaut, Marshall Cooper, Susan F. Fenton, Matthew J. Arshad, S. Hasan Bahna, Sami L. Beck, Lisa A. Byrd-Bredbenner, Carol Camargo, Carlos A., Jr. Eichenfield, Lawrence Furuta, Glenn T. Hanifin, Jon M. Jones, Carol Kraft, Monica Levy, Bruce D. Lieberman, Phil Luccioli, Stefano McCall, Kathleen M. Schneider, Lynda C. Simon, Ronald A. Simons, F. Estelle R. Teach, Stephen J. Yawn, Barbara P. Schwaninger, Julie M. TI Guidelines for the Diagnosis and Management of Food Allergy in the United States: Summary of the NIAID-Sponsored Expert Panel Report SO NUTRITION RESEARCH LA English DT Article C1 [Plaut, Marshall; Cooper, Susan F.; Fenton, Matthew J.; Schwaninger, Julie M.] NIAID, Div Allergy Immunol & Transplantat, NIH, Bethesda, MD 20892 USA. [Boyce, Joshua A.] Harvard Univ, Brigham & Womens Hosp, Massachusetts Gen Hosp, Dept Med,Sch Med,Div Rheumatol Immunol & Allergy, Boston, MA 02115 USA. [Camargo, Carlos A., Jr.] Harvard Univ, Dept Emergency Med, Massachusetts Gen Hosp, Dept Med,Div Rheumatol Allergy & Immunol,Sch Med, Boston, MA 02115 USA. [Levy, Bruce D.] Brigham & Womens Hosp, Pulm & Crit Med Div, Partners Asthma Ctr, Boston, MA 02115 USA. [Assa'ad, Amal] Univ Cincinnati, Cincinnati Childrens Hosp Med Ctr, Div Allergy & Immunol, Cincinnati, OH USA. [Burks, A. Wesley] Duke Univ, Med Ctr, Dept Pediat, Div Allergy & Immunol, Durham, NC 27710 USA. [Kraft, Monica] Duke Univ, Med Ctr, Dept Med, Div Pulm Allergy & Crit Care Med, Durham, NC 27710 USA. [Jones, Stacie M.] Univ Arkansas Med Sci, Arkansas Childrens Hosp, Dept Pediat, Div Allergy & Immunol, Little Rock, AR 72205 USA. [Sampson, Hugh A.] Mt Sinai Sch Med, Dept Pediat, Div Allergy & Immunol, Elliot & Roslyn Jaffe Food Allergy Inst, New York, NY USA. [Wood, Robert A.] Johns Hopkins Univ, Sch Med, Dept Pediat, Div Allergy & Immunol, Baltimore, MD 21205 USA. [Arshad, S. Hasan] Univ Southampton, Sch Med, Southampton, Hants, England. [Arshad, S. Hasan] St Marys Hosp, David Hide Asthma & Allergy Res Ctr, Newport, Wight, England. [Arshad, S. Hasan] Southampton Univ Hosp NHS Trust, Southampton, Hants, England. [Bahna, Sami L.] Louisiana State Univ, Hlth Sci Ctr, Dept Pediat, Allergy & Immunol Sect, Shreveport, LA 71105 USA. [Beck, Lisa A.] Univ Rochester, Dept Dermatol, Med Ctr, Rochester, NY 14627 USA. [Byrd-Bredbenner, Carol] Rutgers State Univ, Dept Nutr Sci, New Brunswick, NJ 08903 USA. [Eichenfield, Lawrence] Rady Childrens Hosp, Div Pediat & Adolescent Dermatol, San Diego, CA USA. [Eichenfield, Lawrence] Univ Calif San Diego, Dept Pediat, San Diego, CA 92103 USA. [Eichenfield, Lawrence] Univ Calif San Diego, Dept Med, San Diego, CA 92103 USA. [Furuta, Glenn T.] Childrens Hosp Denver, Digest Hlth Inst, Sect Pediat Gastroenterol Hepatol & Nutr, Aurora, CO USA. [Furuta, Glenn T.] Natl Jewish Hlth, Dept Pediat, Denver, CO USA. [Furuta, Glenn T.] Univ Colorado Denver, Sch Med, Dept Pediat, Aurora, CO USA. [Hanifin, Jon M.] Oregon Hlth & Sci Univ, Dept Dermatol, Portland, OR 97201 USA. [Jones, Carol] Allergy & Asthma Network Mothers Asthmat, Mclean, VA USA. [Lieberman, Phil] Univ Tennessee, Dept Med, Coll Med, Div Allergy & Immunol, Memphis, TN 38104 USA. [Luccioli, Stefano] US FDA, Off Food Addit Safety, College Pk, MD USA. [McCall, Kathleen M.] Childrens Hosp Orange Cty, Orange, CA 92668 USA. [Schneider, Lynda C.] Childrens Hosp Boston, Div Immunol, Boston, MA USA. [Simon, Ronald A.] Scripps Clin, Div Allergy Asthma & Immunol, San Diego, CA USA. [Simons, F. Estelle R.] Univ Manitoba, Fac Med, Dept Pediat, Winnipeg, MB, Canada. [Simons, F. Estelle R.] Univ Manitoba, Fac Med, Dept Child Hlth & Immunol, Winnipeg, MB, Canada. [Teach, Stephen J.] Childrens Natl Med Ctr, Div Emergency Med, Washington, DC 20010 USA. [Yawn, Barbara P.] Olmsted Med Ctr, Dept Res, Rochester, MN USA. [Yawn, Barbara P.] Univ Minnesota, Sch Med, Dept Family & Community Hlth, Minneapolis, MN 55455 USA. RP Fenton, MJ (reprint author), NIAID, Div Allergy Immunol & Transplantat, NIH, 6610 Rockledge Dr,Room 3105, Bethesda, MD 20892 USA. EM fentonm@niaid.nih.gov RI Byrd-Bredbenner, Carol/F-8064-2015 OI Byrd-Bredbenner, Carol/0000-0002-8010-3987 FU National Institutes of Health; GlaxoSmithKline; Food Allergy and Anaphylaxis Network; Gerber; Mead Johnson; Dyax Corp; National Peanut Board; Food Allergy Initiative; National Institutes of Health (Division of Receipt and Referral, National Institute of Allergy and Infectious Diseases, National Center for Complementary and Alternative Medicine); Phadia AB; Genentech; National Institutes of Health (National Institute of Allergy and Infectious Diseases); National Institute of Health Research, UK; American Academy of Allergy, Asthma, and Immunology; National Eczema Association; US Department of Agriculture; Canned Food Alliance; New Jersey Department of Health and Senior Services; variety of government agencies; Dey; Novartis; Astellas; Ferndale; Johnson Johnson; Sinclair; Stiefel; Therapeutics Inc FX J. A. Boyce has served on the Advisory Board of GlaxoStmithKline. He has served as a consultant and/or speaker for Altana, GlaxoSmithKline, and Merck. He has received funding/grant support from the National Institutes of Health.; A. Assa'ad holds, or is listed as an inventor on, US patent application #10/566903, entitled "Genetic markers of food allergy." She has served as a consultant for GlaxoStmithKline and as a speaker for the American College of Allergy, Asthma, and Immunology, the North East Allergy Society, the Virginia Allergy Society, the New England Allergy Society, and the American Academy of Pediatrics. Dr Assa'ad has received funding/grant support from GlaxoSmithKline.; A. W. Burks holds, or is listed as an inventor on, multiple US patents related to food allergy. He owns stock in Allertein and MastCell, Inc, and is a minority stockholder in Daimon Co Probiotics. He has served as a consultant for ActoGeniX NV, McNeil Nutritionals, Mead Johnson, and Novartis. He has served on the speaker's bureau for EpiPen/Dey, LP, and has served on the data monitoring committee for Genentech. He has served on an expert panel for Nutricia. Dr Burks has received funding/grant support from the Food Allergy and Anaphylaxis Network, Gerber, Mead Johnson, and the National Institutes of Health.; S. M. Jones has served as a speaker and grant reviewer and has served on the medical advisory committee for the Food Allergy and Anaphylaxis Network. She has received funding/grant support from Dyax Corp, the Food Allergy and Anaphylaxis Network, Mead Johnson, the National Peanut Board, and the National Institutes of Health.; H. A. Sampson holds, or is listed as an inventor on, multiple US patents related to food allergy. He owns stock in Allertein Therapeutics. He is the immediate past president of the American Academy of Allergy, Asthma, and Immunology. He has served as a consultant for Allertein Therapeutics, the American Academy of Allergy, Asthma, and Immunology, the Food Allergy Initiative, and Schering Plough. He has received funding/grant support for research projects from the Food Allergy Initiative, the National Institutes of Health (Division of Receipt and Referral, National Institute of Allergy and Infectious Diseases, National Center for Complementary and Alternative Medicine), and Phadia AB. He is a co-owner of Herbal Spring, LLC.; R. A. Wood has served as a speaker/advisory board member for GlaxoSmithKline, Merck, and Dey. He has received funding/grant support from Genentech and the National Institutes of Health (National Institute of Allergy and Infectious Diseases).; S. H. Arshad has received funding/grant support from the National Institutes of Health and the National Institute of Health Research, UK.; S. L. Bahna has received funding/grant support from Genentech.; L. A. Beck has received funding/grant support from the American Academy of Allergy, Asthma, and Immunology, the National Eczema Association, and the National Institutes of Health.; C. Byrd-Bredbenner owns stock in Johnson & Johnson. She has received funding/grant support from the US Department of Agriculture, the Canned Food Alliance, and the New Jersey Department of Health and Senior Services.; C. A. Camargo Jr has consulted for Dey and Novartis. He has received funding/grant support from a variety of government agencies and not-for-profit research foundations, as well as Dey and Novartis.; L. Eichenfield has received funding/grant support from a variety of not-for-profit foundations, as well as Astellas, Ferndale, Johnson & Johnson, Novartis, Sinclair, Stiefel, and Therapeutics Inc. NR 1 TC 33 Z9 39 U1 0 U2 8 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0271-5317 J9 NUTR RES JI Nutr. Res. PD JAN PY 2011 VL 31 IS 1 BP 61 EP 75 DI 10.1016/j.nutres.2011.01.001 PG 15 WC Nutrition & Dietetics SC Nutrition & Dietetics GA 724ZB UT WOS:000287613900010 PM 21310308 ER PT S AU Heindel, JJ AF Heindel, Jerrold J. BE Lustig, RH TI The Obesogen Hypothesis of Obesity: Overview and Human Evidence SO OBESITY BEFORE BIRTH: MATERNAL AND PRENATAL INFLUENCES ON THE OFFSPRING SE Endocrine Updates LA English DT Article; Book Chapter ID MATERNAL SMOKING; INTRAUTERINE EXPOSURE; DEVELOPMENTAL ORIGINS; METABOLIC SYNDROME; CHILD OVERWEIGHT; PREGNANCY; HEALTH; FETAL; FRUCTOSE; DISEASE C1 Natl Inst Environm Hlth Sci, Div Extramural Res & Training, Res Triangle Pk, NC USA. RP Heindel, JJ (reprint author), Natl Inst Environm Hlth Sci, Div Extramural Res & Training, Res Triangle Pk, NC USA. EM heindelj@niehs.nih.gov NR 46 TC 7 Z9 8 U1 0 U2 5 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013, UNITED STATES SN 1566-0729 BN 978-1-4419-7033-6 J9 ENDOCR UPDAT PY 2011 BP 355 EP 365 DI 10.1007/978-1-4419-7034-3_17 D2 10.1007/978-1-4419-7034-3 PG 11 WC Endocrinology & Metabolism; Obstetrics & Gynecology SC Endocrinology & Metabolism; Obstetrics & Gynecology GA BRK21 UT WOS:000282900300017 ER PT J AU Harper, M Zheng, SL Thom, E Klebanoff, MA Thorp, J Sorokin, Y Varner, MW Iams, JD Dinsmoor, M Mercer, BM Rouse, DJ Ramin, SM Anderson, GD AF Harper, Margaret Zheng, S. Lilly Thom, Elizabeth Klebanoff, Mark A. Thorp, John, Jr. Sorokin, Yoram Varner, Michael W. Iams, Jay D. Dinsmoor, Mara Mercer, Brian M. Rouse, Dwight J. Ramin, Susan M. Anderson, Garland D. CA Eunice Kennedy Shriver Natl Inst TI Cytokine Gene Polymorphisms and Length of Gestation SO OBSTETRICS AND GYNECOLOGY LA English DT Article ID NECROSIS-FACTOR-ALPHA; SPONTANEOUS PRETERM DELIVERY; PROMOTER POLYMORPHISM; INTRAUTERINE INFECTION; BIRTH; ASSOCIATION; DISEASE; CHORIOAMNIONITIS; PARTURITION; RECEPTOR AB OBJECTIVE: To estimate whether there is an association between length of gestation and gene polymorphisms that effect transcription of tumor necrosis factor-alpha (TNF-alpha), interleukin-6 (IL-6), or interleukin-1 beta (IL-1 beta). METHODS: Blood for DNA analysis was collected from 834 women at high risk enrolled in a randomized, clinical trial of omega-3 fatty acid supplementation for the prevention of recurrent preterm birth. Genotyping was performed for three single nucleotide polymorphisms (SNPs), TNF-alpha -308, IL-6 -174, and IL-1 beta +3954. Women with the homozygous minor genotype were compared with women with either the heterozygous or the homozygous major genotype. Kaplan-Meier curves of gestational age at delivery and odds ratios for extreme preterm delivery were adjusted for African-American race and treatment group. RESULTS: Women who were homozygous for the minor allele at the -308 position in the promoter region of the TNF-alpha gene had significantly shorter length of gestation than women who were either heterozygous or homozygous for the major allele (adjusted hazard ratio 1.74, 95% confidence interval [CI] 1.04-2.90, P=.03). Among women with this genotype, 20% (3/15) experienced extreme spontaneous preterm delivery (less than 28 weeks of gestation; adjusted odds ratio 7.51, 95% CI 1.84-30.72, P=.005). There was no difference in length of gestation or risk of extreme spontaneous preterm delivery by genotype for the IL-6 -174 or the IL-1 beta +3954 SNP. CONCLUSION: Polymorphism at the -308 position in the TNF-alpha promoter region is associated with shorter gestation and an increased risk of spontaneous extreme preterm delivery. C1 Wake Forest Univ Hlth Sci, Dept Obstet & Gynecol, Winston Salem, NC USA. Wake Forest Univ Hlth Sci, Ctr Human Genom, Winston Salem, NC USA. Univ N Carolina, Dept Obstet & Gynecol, Chapel Hill, NC USA. Wayne State Univ, Detroit, MI USA. Univ Utah, Hlth Sci Ctr, Salt Lake City, UT USA. Ohio State Univ, Columbus, OH 43210 USA. Northwestern Univ, Chicago, IL 60611 USA. Case Western Reserve Univ, Metrohlth Med Ctr, Cleveland, OH USA. Univ Alabama, Birmingham, AL USA. Univ Texas Hlth Sci Ctr Houston, Houston, TX USA. Univ Texas Med Branch, Galveston, TX USA. George Washington Univ, Ctr Biostat, Washington, DC USA. Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Bethesda, MD USA. RP Harper, M (reprint author), Mt Area Hlth Educ Ctr, 900 Hendersonville Rd,Suite 206, Asheville, NC 28803 USA. EM harper.margaret@gmail.com RI Varner, Michael/K-9890-2013 OI Varner, Michael/0000-0001-9455-3973 FU Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) [HD27860, HD27917, HD40560, HD34208, HD40485, HD21410, HD27915, HD40500, HD40512, HD40544, MO1-relative risk-000080, HD34136, HD27869, HD40545, HD36801, HD19897] FX Supported by grants from the Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) (HD27860, HD27917, HD40560, HD34208, HD40485, HD21410, HD27915, HD40500, HD40512, HD40544, MO1-relative risk-000080, HD34136, HD27869, HD40545, HD36801, HD19897). The views in this article do not necessarily represent the official views of the NICHD or the National Institutes of Health. NR 37 TC 9 Z9 10 U1 0 U2 4 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0029-7844 J9 OBSTET GYNECOL JI Obstet. Gynecol. PD JAN PY 2011 VL 117 IS 1 BP 125 EP 130 DI 10.1097/AOG.0b013e318202b2ef PG 6 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 697GI UT WOS:000285500800018 PM 21173653 ER PT J AU Bhatti, P Stewart, PA Linet, MS Blair, A Inskip, PD Rajaraman, P AF Bhatti, Parveen Stewart, Patricia A. Linet, Martha S. Blair, Aaron Inskip, Peter D. Rajaraman, Preetha TI Comparison of occupational exposure assessment methods in a case-control study of lead, genetic susceptibility and risk of adult brain tumours SO OCCUPATIONAL AND ENVIRONMENTAL MEDICINE LA English DT Article ID ENVIRONMENT INTERACTION; RETROSPECTIVE EVALUATION; SAMPLE-SIZE; MATRIX; INFORMATION; POPULATION; HISTORIES; CANCER; MODEL AB Objectives There is great interest in evaluating gene-environment interactions with chemical exposures, but exposure assessment poses a unique challenge in case-control studies. Expert assessment of detailed work history data is usually considered the best approach, but it is a laborious and time-consuming process. We set out to determine if a less intensive method of exposure assessment (a job exposure matrix (JEM)) would produce similar results to a previous analysis that found evidence of effect modification of the association between expert-assessed lead exposure and risk of brain tumours by a single nucleotide polymorphism in the ALAD gene (rs1800435). Methods We used data from a study of 355 patients with glioma, 151 patients with meningioma and 505 controls. Logistic regression models were used to examine associations between brain tumour risk and lead exposure and effect modification by genotype. We evaluated Cohen's kappa, sensitivity and specificity for the JEM compared to the expert-assessed exposure metrics. Results Although effect estimates were imprecise and driven by a small number of cases, we found evidence of effect modification between lead exposure and ALAD genotype when using expert-but not JEM-derived lead exposure estimates. kappa Values indicated only modest agreement (<0.5) for the exposure metrics, with the JEM indicating high specificity (similar to 0.9) but poor sensitivity (similar to 0.5). Disagreement between the two methods was generally due to having additional information in the detailed work history. Conclusion These results provide preliminary evidence suggesting that high quality exposure data are likely to improve the ability to detect genetic effect modification. C1 [Bhatti, Parveen] Fred Hutchinson Canc Res Ctr, Program Epidemiol, Div Publ Hlth Sci, Seattle, WA 98109 USA. [Stewart, Patricia A.] Stewart Exposure Assessments LLC, Arlington, VA USA. [Linet, Martha S.; Blair, Aaron; Inskip, Peter D.; Rajaraman, Preetha] NCI, Div Canc Epidemiol & Genet, NIH, DHHS, Bethesda, MD 20892 USA. RP Bhatti, P (reprint author), Fred Hutchinson Canc Res Ctr, Program Epidemiol, Div Publ Hlth Sci, POB 19024,M4-B874, Seattle, WA 98109 USA. EM pbhatti@fhcrc.org FU National Cancer Institute, National Institutes of Health, Department of Health and Human Services [N01-CO-12400] FX This study was funded under contract N01-CO-12400 from the Intramural Research Program of the National Cancer Institute, National Institutes of Health, Department of Health and Human Services. NR 29 TC 9 Z9 10 U1 1 U2 4 PU B M J PUBLISHING GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 1351-0711 J9 OCCUP ENVIRON MED JI Occup. Environ. Med. PD JAN PY 2011 VL 68 IS 1 BP 4 EP 9 DI 10.1136/oem.2009.048132 PG 6 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 692VE UT WOS:000285182900003 PM 20798009 ER PT J AU Dwyer, J Le Guelte, A Moya, EMG Sumbal, M Carlotti, A Douguet, L Gutkind, JS Grange, PA Dupin, N Gavard, J AF Dwyer, J. Le Guelte, A. Moya, E. M. Galan Sumbal, M. Carlotti, A. Douguet, L. Gutkind, J. S. Grange, P. A. Dupin, N. Gavard, J. TI Remodeling of VE-cadherin junctions by the human herpes virus 8 G-protein coupled receptor SO ONCOGENE LA English DT Article DE cell junctions; permeability; rac; PI(3)K; VE-cadherin; kaposi sarcoma ID SARCOMA-ASSOCIATED-HERPESVIRUS; KAPOSIS-SARCOMA; ENDOTHELIAL PERMEABILITY; VASCULAR-PERMEABILITY; PARACRINE NEOPLASIA; ADHERENS JUNCTIONS; GENE-EXPRESSION; GROWTH-FACTOR; CELL; VGPCR AB Kaposi Sarcoma (KS) are opportunistic tumors, associated with human herpes virus 8 (HHV8) infection. KS development is highly favored by immune-depression and remains the second most frequent tumor in acquired immune deficiency syndrome patients. Although it has been shown that experimental expression of the HHV8 G-protein-coupled receptor (vGPCR) in the endothelial compartment is alone sufficient to recapitulate the formation and progression of KS-like lesions, its functional effects on endothelial homeostasis are not fully understood. Here we show that vGPCR expression in endothelial cells induces an increase in paracellular permeability both in vivo and in vitro. By using pharmacological inhibitors and small interference RNA-based knockdown, we demonstrate an essential role for the PI(3)Kinase-gamma/Rac nexus in vGPCR-mediated permeability. This was further accompanied by dramatic remodeling of VE-cadherin-dependent cell-cell junctions. Importantly, this in vitro vGPCR-initiated signaling signature was observed in a large panel of human KS. Altogether, our results support the hypothesis that endothelial vGPCR signaling is co-opted in KS, and unveil new key cellular targets for therapeutic intervention. Oncogene (2011) 30, 190-200; doi: 10.1038/onc.2010.411; published online 6 September 2010 C1 [Dwyer, J.; Le Guelte, A.; Moya, E. M. Galan; Sumbal, M.; Douguet, L.; Gavard, J.] Univ Paris 05, Inst Cochin, CNRS UMR 8104, INSERM,U1016, F-75014 Paris, France. [Carlotti, A.] Univ Paris 05, Grp Hosp Cochin Port Royal, AP HP, Serv Anat & Cytol Pathol,Fac Med, F-75014 Paris, France. [Gutkind, J. S.] Natl Inst Dent & Craniofacial Res, Oral & Pharyngeal Canc Branch, NIH, Bethesda, MD USA. [Grange, P. A.; Dupin, N.] Univ Paris 05, Lab Rech Dermatol, EA 1833, Fac Med, F-75014 Paris, France. [Dupin, N.] Univ Paris 05, Grp Hosp Cochin Port Royal Pavillon Tarnier, AP HP, Serv Dermatol,Fac Med, F-75014 Paris, France. RP Gavard, J (reprint author), Univ Paris 05, Inst Cochin, CNRS UMR 8104, INSERM,U1016, 22 Rue Mechain,Rm 306, F-75014 Paris, France. EM julie.gavard@inserm.fr RI Gutkind, J. Silvio/A-1053-2009; Gavard, Julie/I-5487-2012; OI Gavard, Julie/0000-0002-7985-9007; Galan-Moya, Eva M/0000-0001-5758-7592 FU Ligue Nationale contre le Cancer, comite de Paris; European Community [PIRG04-GA-2008-239126]; Fondation pour la Recherche Medicale; Association pour la Recherche sur le Cancer FX We would like to thank N. Bidere (Inserm U1014, Universite Paris-Sud, Hopital Paul Brousse, Villejuif, France) for helpful discussions and comments, A Schmitt (Institut Cochin, Paris, France) for technical help on electron microscopy experiments, Anne Audebourg and Brigitte Radenen (Service d'Anatomie et de Cytologie Pathologique, Hopital Cochin, Paris, France) for technical help on histological staining, and Nina Feinberg (OPCB, NIDCR, NIH, Bethesda, MD, USA) for technical help on the initial project. This research was funded by Ligue Nationale contre le Cancer, comite de Paris and by a Marie Curie International Reintegration Grant within the 7th European Community Framework Programme (PIRG04-GA-2008-239126). JD is supported by a post-doctoral fellowship from Fondation pour la Recherche Medicale, ALG by the PhD program from Universite Paris 5 and EMGM by a post-doctoral fellowship from Association pour la Recherche sur le Cancer. NR 38 TC 19 Z9 19 U1 0 U2 2 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0950-9232 J9 ONCOGENE JI Oncogene PD JAN PY 2011 VL 30 IS 2 BP 190 EP 200 DI 10.1038/onc.2010.411 PG 11 WC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity GA 709LG UT WOS:000286438900007 PM 20818438 ER PT J AU Park, HD Lee, Y Oh, YK Jung, JG Park, YW Myung, K Kim, KH Koh, SS Lim, DS AF Park, H. D. Lee, Y. Oh, Y. K. Jung, J. G. Park, Y. W. Myung, K. Kim, K-H Koh, S. S. Lim, D-S TI Pancreatic adenocarcinoma upregulated factor promotes metastasis by regulating TLR/CXCR4 activation SO ONCOGENE LA English DT Article DE PAUF; TLR; CXCR4; TPL2; ERK; NF-kappa B ID TOLL-LIKE RECEPTORS; TUMOR-GROWTH; CARBOHYDRATE SPECIFICITIES; STRUCTURAL BASIS; BINDING LECTINS; CANCER-CELLS; ANGIOGENESIS; LIPOPOLYSACCHARIDE; INFLAMMATION; PROGRESSION AB Pancreatic adenocarcinoma upregulated factor (PAUF) is overproduced in certain types of cancer. However, little is known of the tumorigenic function of PAUF. In this study, we report the X-ray crystal structure of PAUF and reveal that PAUF is a mammalian lectin normally found in plant lectins. We also identify PAUF as an endogenous ligand of Toll-like receptor 2 (TLR2) and TLR4 by screening extracellular domain receptor pools. We further confirmed the specificity of the PAUF-TLR2 interaction. PAUF induces extracellular signal-regulated kinase (ERK) phosphorylation and activates the IKK-beta-mediated TPL2/MEK/ERK signaling pathway through TLR2. In agreement with the result of TLR2-mediated ERK activation by PAUF, PAUF induces increased expression of the protumorigenic cytokines RANTES and MIF in THP-1 cells. However, PAUF does not fully activate I kappa-B-alpha signaling pathways in THP-1 cells, and fails to translocate the p65 subunit of the nuclear factor-kappa B (NF-kappa B) complex into the nucleus, resulting in no NF-kappa B activation. Surprisingly, we found that PAUF also associated with the CXC chemokine receptor (CXCR4)-TLR2 complex and inhibited CXCR4-dependent, TLR2-mediated NF-kappa B activation. Together, these findings suggest that the new cancer-associated ligand, PAUF, may activate TLR-mediated ERK signaling to produce the protumorigenic cytokines, but inhibits TLR-mediated NF-kappa B signaling, thereby facilitating tumor growth and escape from innate immune surveillance. Oncogene (2011) 30, 201-211; doi:10.1038/onc.2010.401; published online 30 August 2010 C1 [Lee, Y.; Jung, J. G.; Park, Y. W.; Kim, K-H; Koh, S. S.] Korea Res Inst Biosci & Biotechnol, Therapeut Antibody Res Ctr, Taejon, South Korea. [Park, H. D.; Lee, Y.; Lim, D-S] Natl Creat Res Initiat Ctr Cell Div & Differentia, Dept Biol Sci, Taejon, South Korea. [Park, H. D.; Oh, Y. K.] LG Life Sci, Dept Pharmacol, Taejon, South Korea. [Myung, K.] NHGRI, NIH, Bethesda, MD 20892 USA. RP Koh, SS (reprint author), Korea Res Inst Biosci & Biotechnol, Therapeut Antibody Res Ctr, Taejon, South Korea. EM sskoh@kribb.re.kr; daesiklim@kaist.ac.kr RI Lim, Dae-Sik/C-1599-2011 OI Lim, Dae-Sik/0000-0003-2356-7555 FU National Creative Research Initiative Center; World Class University (WCU); Ministry of Education, Science and Technology in Korea FX This study was supported by grants from the National Creative Research Initiative Center Program, World Class University (WCU) program and the 21st Century Frontier Functional Human Genome Project of the Ministry of Education, Science and Technology in Korea. We thank Sang Yong Hong for technical support with the cloning work. We thank the staff of Beamline 4A at the Pohang Accelerator Laboratory, Korea, for assistance in data collection and Dr Hyun Kyu Song of Korea University for help with MAD data analysis. NR 34 TC 46 Z9 47 U1 1 U2 10 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0950-9232 J9 ONCOGENE JI Oncogene PD JAN PY 2011 VL 30 IS 2 BP 201 EP 211 DI 10.1038/onc.2010.401 PG 11 WC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity GA 709LG UT WOS:000286438900008 PM 20802527 ER PT J AU DeCicco-Skinner, KL Trovato, EL Simmons, JK Lepage, PK Wiest, JS AF DeCicco-Skinner, K. L. Trovato, E. L. Simmons, J. K. Lepage, P. K. Wiest, J. S. TI Loss of tumor progression locus 2 (tpl2) enhances tumorigenesis and inflammation in two-stage skin carcinogenesis SO ONCOGENE LA English DT Article DE Tpl2; skin cancer; inflammation; MAP3K8; NF-kappa B ID NF-KAPPA-B; PROTEIN-KINASE-C; NF-KAPPA-B1 P105; MOUSE SKIN; SIGNALING PATHWAYS; CANCER DEVELOPMENT; TRANSGENIC MICE; T-CELLS; IN-VIVO; ACTIVATION AB Tumor progression locus 2 (Tpl2) is a serine/threonine kinase in the mitogen-activated protein kinase signal transduction cascade known to regulate inflammatory pathways. Previously identified as an oncogene, its mutation or overexpression is reported in a variety of human cancers. To address its role in skin carcinogenesis, Tpl2(-/-) or wild-type (WT) C57BL/6 mice were subjected to a two-stage dimethylbenzanthracene/12-O-tetradecanoylphorbol- 13-acetate (TPA) mouse skin carcinogenesis model. Tpl2(-/-) mice developed a significantly higher incidence of tumors (80%) than WT mice (17%), as well as a reduced tumor latency and a significantly higher number of total tumors (113 vs 6). Moreover, Tpl2(-/-) mice treated with TPA experienced significantly higher nuclear factor kappaB (NF-kappa B) activation, edema, infiltrating neutrophils and production of proinflammatory cytokines than did WT mice. We investigated the role of the p38, JNK, MEK and NF-kappa B signaling pathways both in vitro and in vivo in WT and Tpl2(-/-) mice by using inhibitors for each of these pathways. We confirmed that the proinflammatory effect in Tpl2(-/-) mice was due to heightened activity of the NF-kappa B pathway. These studies indicate that Tpl2 may serve more as a tumor suppressor than as an oncogene in chemically induced skin carcinogenesis, with its absence contributing to both tumorigenesis and inflammation. Oncogene (2011) 30, 389-397; doi: 10.1038/onc.2010.447; published online 11 October 2010 C1 [DeCicco-Skinner, K. L.; Trovato, E. L.] NCI, Lab Canc Biol & Genet, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. [Trovato, E. L.; Simmons, J. K.; Lepage, P. K.; Wiest, J. S.] American Univ, Dept Biol, Washington, DC 20016 USA. RP Wiest, JS (reprint author), NCI, Lab Canc Biol & Genet, Ctr Canc Res, NIH, 37 Convent Dr, Bethesda, MD 20892 USA. EM wiestj@mail.nih.gov FU NCI/NIH FX We thank Dr Jyotsna Pandey for her assistance with confocal microscopy. This work was supported by the NCI/NIH Intramural Research Program. NR 44 TC 11 Z9 11 U1 2 U2 3 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0950-9232 J9 ONCOGENE JI Oncogene PD JAN PY 2011 VL 30 IS 4 BP 389 EP 397 DI 10.1038/onc.2010.447 PG 9 WC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity GA 711WH UT WOS:000286621600002 PM 20935675 ER PT J AU Schug, TT AF Schug, Thaddeus T. TI Targeting Transcription Through Inhibition of TBP SO ONCOTARGET LA English DT Editorial Material ID RNA-POLYMERASE-II C1 NIEHS, Div Extramural Res & Training, Cellular Organ & Syst Pathobiol Branch, Res Triangle Pk, NC 27709 USA. RP Schug, TT (reprint author), NIEHS, Div Extramural Res & Training, Cellular Organ & Syst Pathobiol Branch, POB 12233, Res Triangle Pk, NC 27709 USA. EM Schugt@niehs.nih.gov NR 9 TC 1 Z9 1 U1 0 U2 0 PU IMPACT JOURNALS LLC PI ALBANY PA 6211 TIPTON HOUSE, STE 6, ALBANY, NY 12203 USA SN 1949-2553 J9 ONCOTARGET JI Oncotarget PD JAN-FEB PY 2011 VL 2 IS 1-2 BP 5 EP 7 PG 3 WC Oncology; Cell Biology SC Oncology; Cell Biology GA 802JT UT WOS:000293507100002 PM 21378415 ER PT J AU Charles, BA Conley, YP Chen, GJ Miller, RG Dorman, JS Gorin, MB Ferrell, RE Sereika, SM Rotimi, CN Orchard, TJ AF Charles, Bashira A. Conley, Yvette P. Chen, Guanjie Miller, Rachel G. Dorman, Janice S. Gorin, Michael B. Ferrell, Robert E. Sereika, Susan M. Rotimi, Charles N. Orchard, Trevor J. TI Variants of the Adenosine A(2A) Receptor Gene Are Protective against Proliferative Diabetic Retinopathy in Patients with Type 1 Diabetes SO OPHTHALMIC RESEARCH LA English DT Article DE Diabetes; Diabetic retinopathy; Single nucleotide polymorphism; Adenosine receptor ID ENDOTHELIAL GROWTH-FACTOR; NON-HISPANIC WHITES; PITTSBURGH EPIDEMIOLOGY; ADVANCED GLYCATION; FACTOR EXPRESSION; COMPLICATIONS; ACTIVATION; CELLS; MELLITUS; RISK AB Aims: The adenosine A(2A) receptor (ADORA(2A)) may ameliorate deleterious physiologic effects associated with tissue injury in individuals with diabetes. We explored associations between variants of the ADORA(2A) gene and proliferative diabetic retinopathy (PDR) in a cohort of patients with type 1 diabetes (T1D). Methods: The participants were from the Pittsburgh Epidemiology of Diabetes Complications prospective study of childhood-onset T1D. Stereoscopic photographs of the retinal fundus taken at baseline, then biennially, for 10 years were used to define PDR according to the modified Airlie House system. Two tagging single nucleotide polymorphisms (tSNPs; rs2236624-C/T and rs4822489-G/T) in the ADORA(2A) gene were selected using the HapMap (haplotype map) reference database. Results: A significant association was observed between SNP rs2236624 and PDR in the recessive genetic model. Participants homozygous for the T allele displayed a decreased risk of developing prevalent PDR (odds ratio, OR = 0.36; p = 0.04) and incident PDR (hazard ratio = 0.156; p = 0.009), and for all cases of PDR combined (OR = 0.23; p = 0.001). The protective effect of T allele homozygosity remained after adjusting for covariates. Similarly, for SNP rs4822489, an association between PDR and T allele homozygosity was observed following covariate adjustment (OR = 0.55; 95% CI: 0.31-0.92; p = 0.04). Conclusion: Genetic variants of ADORA(2A) offer statistically significant protection against PDR development in patients with T1D. Copyright (C) 2010 S. Karger AG, Basel C1 [Charles, Bashira A.; Chen, Guanjie; Rotimi, Charles N.] Natl Human Genome Res Inst, Ctr Res Genom & Global Hlth, NIH, Bethesda, MD 20892 USA. [Charles, Bashira A.] NINR, NIH, Bethesda, MD 20892 USA. [Charles, Bashira A.; Conley, Yvette P.; Miller, Rachel G.; Dorman, Janice S.; Ferrell, Robert E.; Sereika, Susan M.; Orchard, Trevor J.] Univ Pittsburgh, Pittsburgh, PA USA. [Gorin, Michael B.] Jules Stein Eye Inst, Los Angeles, CA 90024 USA. [Gorin, Michael B.] Univ Calif Los Angeles, Los Angeles, CA USA. RP Charles, BA (reprint author), Natl Human Genome Res Inst, Ctr Res Genom & Global Hlth, NIH, Bldg 12A,Room 4047,12 S Dr,MSC 5635, Bethesda, MD 20892 USA. EM charlesba@mail.nih.gov OI orchard, trevor/0000-0001-9552-3215 FU NIH/National Institute of Nursing Research [1F31NR008970-01A2]; American Nurses Foundation; NIH/National Institute of Diabetes and Digestive and Kidney Diseases [R01 DK034818-21]; National Human Genome Research Institute, NIH, in the Center for Research in Genomics and Global Health [Z01HG200362] FX We would like to thank/acknowledge Dr. Adebowale Adeyemo, Deputy Director, of the Center for Research on Genomics and Global Health, National Human Genome Research Institute, National Institutes of Health (NIH), for his contributions to the manuscript. This research was conducted at the University of Pittsburgh and supported by grants NIH/National Institute of Nursing Research 1F31NR008970-01A2 'Genetic Basis of Diabetic Retinopathy', Charles B. (PI), American Nurses Foundation 'Genes Implicated in Time to Onset and Severity of Diabetic Retinopathy', Charles B. (PI), and NIH/National Institute of Diabetes and Digestive and Kidney Diseases R01 DK034818-21 'Epidemiology of Diabetes Complications, Phase II', Orchard (PI). This research was also supported in part by the Intramural Research Program of the National Human Genome Research Institute, NIH, in the Center for Research in Genomics and Global Health (Z01HG200362). NR 52 TC 4 Z9 4 U1 0 U2 4 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 0030-3747 J9 OPHTHALMIC RES JI Ophthalmic Res. PY 2011 VL 46 IS 1 BP 1 EP 8 DI 10.1159/000317057 PG 8 WC Ophthalmology SC Ophthalmology GA 782TW UT WOS:000292035800001 PM 21088442 ER PT J AU Zheng, C Shinomiya, T Goldsmith, CM Di Pasquale, G Baum, BJ AF Zheng, C. Shinomiya, T. Goldsmith, C. M. Di Pasquale, G. Baum, B. J. TI Convenient and reproducible in vivo gene transfer to mouse parotid glands SO ORAL DISEASES LA English DT Article DE parotid; gene transfer; adenoviral vector; mouse ID ACID-ALPHA-GLUCOSIDASE; DISEASE TYPE-II; SALIVARY-GLANDS; ADENOVIRAL VECTOR; KNOCKOUT MICE; EXPRESSION; THERAPEUTICS; SECRETION; RESPONSES; DELIVERY AB Objectives: Published studies of gene transfer to mouse salivary glands have not employed the parotid glands. Parotid glands are the likely target tissue for most clinical applications of salivary gene transfer. The purpose of the present study was to develop a convenient and reproducible method of retroductal gene transfer to mouse parotid glands. Methods: The volume for vector delivery was assessed by infusion of Toluidine Blue into Stensen's ducts of Balb/c mice after direct intraoral cannulation. Recombinant, serotype 5 adenoviral vectors, encoding either firefly luciferase or human erythropoietin (hEpo), were constructed and then administered to parotid glands (107 vector particles/gland). Transgene expression in vivo was measured by enzyme activity (luciferase) or an enzyme-linked immunosorbent assay (hEpo). Vector biodistribution was measured by real-time quantitative (Q) PCR. Results: The chosen volume for mouse parotid vector delivery was 20 mu L. Little vector was detected outside of the targeted glands, with both QPCR and luciferase assays. Transgene expression was readily detected in glands (luciferase, hEpo), and serum and saliva (hEpo). Most secreted hEpo was detected in saliva. Conclusion: These studies show that mouse parotid glands can be conveniently and reproducibly targeted for gene transfer, and should be useful for pre-clinical studies with many murine disease models. C1 [Zheng, C.; Shinomiya, T.; Goldsmith, C. M.; Di Pasquale, G.; Baum, B. J.] NIDCR, MPTB, NIH, Bethesda, MD 20892 USA. RP Baum, BJ (reprint author), NIDCR, MPTB, NIH, Bldg 10,Room 1N113,MSC-1190,10 Ctr Dr, Bethesda, MD 20892 USA. EM bbaum@dir.nidcr.nih.gov FU National Institute of Dental and Craniofacial Research FX This research was supported by the Intramural Research Program of the National Institute of Dental and Craniofacial Research. NR 31 TC 5 Z9 5 U1 0 U2 0 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1354-523X J9 ORAL DIS JI Oral Dis. PD JAN PY 2011 VL 17 IS 1 BP 77 EP 82 DI 10.1111/j.1601-0825.2010.01707.x PG 6 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA 693UK UT WOS:000285250700011 PM 20646229 ER PT J AU Telu, S Chun, JH Simeon, FG Lu, SY Pike, VW AF Telu, Sanjay Chun, Joong-Hyun Simeon, Fabrice G. Lu, Shuiyu Pike, Victor W. TI Syntheses of mGluR5 PET radioligands through the radiofluorination of diaryliodonium tosylates SO ORGANIC & BIOMOLECULAR CHEMISTRY LA English DT Article ID POSITRON-EMISSION-TOMOGRAPHY; GLUTAMATE SUBTYPE-5 RECEPTORS; NEAR-UV PHOTOINITIATOR; PAIR ELECTRON-TRANSFER; SENSITIZED PHOTOLYSIS; DIPHENYLIODONIUM; SALTS; F-18; ION; CHEMISTRY AB 3-Fluoro-1-((thiazol-4-yl) ethynyl) benzenes constitute an important class of high-affinity metabotropic glutamate subtype 5 receptor (mGluR5) ligands, some of which have been labeled with fluorine-18 (t(1/2) = 109.7 min), to provide radioligands for molecular imaging of brain mGluR5 in living animal and human subjects with positron emission tomography (PET). Labeling in the 3-fluoro position of such ligands can be achieved through aromatic nucleophilic substitution of a halide leaving group with [(18)F] fluoride ion when a weakly activating m-nitrile group is present, but is generally very low yielding (< 8%). Here we used a microfluidic reaction platform to show that greatly enhanced (up to 6-fold) radiochemical yields can be achieved from suitably synthesized diaryliodonium tosylate precursors. The presence of a m-nitrile or other activating group is not required. Similar conditions were adopted in a more conventional automated radiochemistry platform having a single-pot reactor, to produce mGluR5 radioligands with useful radioactivities for PET imaging. C1 [Telu, Sanjay; Chun, Joong-Hyun; Simeon, Fabrice G.; Lu, Shuiyu; Pike, Victor W.] NIMH, Mol Imaging Branch, NIH, Bethesda, MD 20892 USA. RP Pike, VW (reprint author), NIMH, Mol Imaging Branch, NIH, Rm B3C346A,10 Ctr Dr, Bethesda, MD 20892 USA. EM pikev@mail.nih.gov OI Lu, Shuiyu/0000-0003-0310-4318 FU National Institutes of Health (NIMH) FX This research was supported by the Intramural Research Program of the National Institutes of Health (NIMH). The authors are grateful to the NIH Clinical Center PET Department (Chief, Dr Peter Herscovitch) for the cyclotron production of fluorine-18. NR 41 TC 27 Z9 27 U1 0 U2 20 PU ROYAL SOC CHEMISTRY PI CAMBRIDGE PA THOMAS GRAHAM HOUSE, SCIENCE PARK, MILTON RD, CAMBRIDGE CB4 0WF, CAMBS, ENGLAND SN 1477-0520 J9 ORG BIOMOL CHEM JI Org. Biomol. Chem. PY 2011 VL 9 IS 19 BP 6629 EP 6638 DI 10.1039/c1ob05555k PG 10 WC Chemistry, Organic SC Chemistry GA 818AL UT WOS:000294720600028 PM 21845279 ER PT J AU Choi, MJ Chandra, G Lee, HW Hou, X Choi, WJ Phan, K Jacobson, KA Jeong, LS AF Choi, Mun Ju Chandra, Girish Lee, Hyuk Woo Hou, Xiyan Choi, Won Jun Khai Phan Jacobson, Kenneth A. Jeong, Lak Shin TI Regio- and stereoselective synthesis of truncated 3 '-aminocarbanucleosides and their binding affinity at the A(3) adenosine receptor SO ORGANIC & BIOMOLECULAR CHEMISTRY LA English DT Article ID L-CYCLOPENTENONE DERIVATIVES; CELL-CYCLE ARREST; CL-IB-MECA; CARBOCYCLIC NUCLEOSIDES; AGONIST; INHIBITION; SULFITES; RADIOLIGAND; APOPTOSIS; SULFATES AB The stereoselective synthesis of truncated 3'-aminocarbanucleosides 4a-d via a stereo- and regioselective conversion of a diol 9 to bromoacetate 11a and their binding affinity towards the human A(3) adenosine receptor are described. C1 [Choi, Mun Ju; Chandra, Girish; Lee, Hyuk Woo; Hou, Xiyan; Choi, Won Jun; Jeong, Lak Shin] Ewha Womans Univ, Coll Pharm, Med Chem Lab, Seoul 120750, South Korea. [Choi, Mun Ju; Chandra, Girish; Lee, Hyuk Woo; Hou, Xiyan; Choi, Won Jun; Jeong, Lak Shin] Ewha Womans Univ, Dept Bioinspired Sci, Seoul 120750, South Korea. [Choi, Won Jun] Dongguk Univ, Coll Pharm, Kyonggi Do 410774, South Korea. [Khai Phan; Jacobson, Kenneth A.] NIDDK, Mol Recognit Sect, Bioorgan Chem Lab, NIH, Bethesda, MD 20892 USA. RP Jeong, LS (reprint author), Ewha Womans Univ, Coll Pharm, Med Chem Lab, Seoul 120750, South Korea. EM lakjeong@ewha.ac.kr RI Jacobson, Kenneth/A-1530-2009 OI Jacobson, Kenneth/0000-0001-8104-1493 FU Korea Research Foundation [NRF-2008-314-E00304, R31-2008-000-10010-0, R15-2006-020]; NIDDK FX This work was supported by the grant from the Korea Research Foundation (NRF-2008-314-E00304, R31-2008-000-10010-0, and R15-2006-020) and the NIDDK Intramural Research program. NR 34 TC 4 Z9 4 U1 0 U2 1 PU ROYAL SOC CHEMISTRY PI CAMBRIDGE PA THOMAS GRAHAM HOUSE, SCIENCE PARK, MILTON RD, CAMBRIDGE CB4 0WF, CAMBS, ENGLAND SN 1477-0520 J9 ORG BIOMOL CHEM JI Org. Biomol. Chem. PY 2011 VL 9 IS 20 BP 6955 EP 6962 DI 10.1039/c1ob05853c PG 8 WC Chemistry, Organic SC Chemistry GA 833MP UT WOS:000295889900016 PM 21860878 ER PT J AU Cappola, AR Hawkes, WG Blocher, N Yu-Yahiro, J Orwig, D Fredman, L Miller, RR Guralnik, JM Magaziner, J AF Cappola, A. R. Hawkes, W. G. Blocher, N. Yu-Yahiro, J. Orwig, D. Fredman, L. Miller, R. R. Guralnik, J. M. Magaziner, J. TI The hormonal profile of hip fracture female patients differs from community-dwelling peers over a 1-year follow-up period SO OSTEOPOROSIS INTERNATIONAL LA English DT Article DE 1,25; Dihydroxyvitamin D; Elderly; Hip fracture; Hormones; IGF-1; Osteocalcin; PTH; Women ID VITAMIN-D-DEFICIENCY; FEMORAL-NECK OSTEOPOROSIS; BONE-MINERAL DENSITY; IGF-I LEVELS; ELDERLY-WOMEN; POSTMENOPAUSAL WOMEN; OLDER WOMEN; CALCIOTROPIC HORMONES; BIOCHEMICAL MARKERS; BINDING-PROTEIN AB Hormone levels were compared over a 1-year period between elderly women who had sustained a hip fracture and women of similar age and functional ability. Our study suggests progressive hormonal changes that may contribute to severe bone loss during the year following hip fracture. Alterations in hormones affecting the musculoskeletal system may increase risk of hip fracture or poor post-fracture recovery in postmenopausal women. Most studies lack appropriate reference groups, and thus cannot assess the extent to which these alterations are attributable to hip fracture. Women aged a parts per thousand yen65 years hospitalized for an acute hip fracture (Baltimore Hip Studies, BHS-3; n = 162) were age-matched to 324 women enrolled in the Women's Health and Aging Study I, a Baltimore-based cohort with similar functional status to the pre-fracture status of BHS-3 women. Both studies enrolled participants from 1992 to 1995. Insulin-like growth hormone-1 (IGF-1), parathyroid hormone (PTH), 1,25 dihydroxyvitamin D [1,25(OH)2D], and osteocalcin were evaluated at baseline and 2, 6, and 12 months post-fracture, and at baseline and 12 months in the comparison group. Between-group differences in trajectories of each hormone were examined. Baseline mean IGF-1 levels were significantly lower in hip fracture patients than the comparison group (75.0 vs. 110.5 mu g/dL; p < 0.001). Levels increased by 2 months post-fracture, but remained significantly lower than those in the comparison group throughout the 12-month follow-up (p < 0.01). Levels of PTH and osteocalcin were similar between groups at baseline, but rose during the year post-fracture to significantly differ from the comparison women (p < 0.001). 1,25(OH)2D levels did not differ between the hip fracture and comparison women at any time. Older women who have sustained a hip fracture have progressive changes in hormonal milieu that exceed those of women of similar health status during the year following fracture. C1 [Cappola, A. R.] Univ Penn Sch Med, Div Endocrinol Diabet & Metab, Philadelphia, PA 19104 USA. [Hawkes, W. G.; Orwig, D.; Miller, R. R.; Magaziner, J.] Univ Maryland, Dept Epidemiol & Prevent Med, Div Gerontol, Baltimore, MD 21201 USA. [Blocher, N.] Albert Einstein Med Ctr, Div Endocrinol, Philadelphia, PA 19141 USA. [Yu-Yahiro, J.] Union Mem Hosp, Dept Orthopaed Surg, Baltimore, MD USA. [Fredman, L.] Boston Univ Sch Publ Hlth, Dept Epidemiol, Boston, MA USA. [Guralnik, J. M.] NIA, Lab Epidemiol Demog & Biometry, Bethesda, MD 20892 USA. RP Cappola, AR (reprint author), Univ Penn Sch Med, Div Endocrinol Diabet & Metab, 764 CRB,415 Curie Blvd, Philadelphia, PA 19104 USA. EM acappola@mail.med.upenn.edu FU National Institute on Aging [K23 AG19161, R37 AG009901, P30 AG028747, N01-AG-1-2112, R37-AG19905]; National Institute on Aging, National Institutes of Health FX This work was supported by the National Institute on Aging K23 AG19161, R37 AG009901, P30 AG028747, contract N01-AG-1-2112, R37-AG19905, and in part by the Intramural Research Program, National Institute on Aging, National Institutes of Health. NR 28 TC 1 Z9 1 U1 0 U2 2 PU SPRINGER LONDON LTD PI LONDON PA 236 GRAYS INN RD, 6TH FLOOR, LONDON WC1X 8HL, ENGLAND SN 0937-941X J9 OSTEOPOROSIS INT JI Osteoporosis Int. PD JAN PY 2011 VL 22 IS 1 BP 339 EP 344 DI 10.1007/s00198-010-1187-4 PG 6 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 703TC UT WOS:000286003200040 PM 20204599 ER PT S AU Aid, S Choi, SH Toscano, CD Bosetti, F AF Aid, Saba Choi, Sang-Ho Toscano, Christopher D. Bosetti, Francesca BE Gadoth, N Gobel, HH TI Distinct Roles of Cyclooxygenase-1 and Cyclooxygenase-2 in Inflammatory and Excitotoxic Brain Injury SO OXIDATIVE STRESS AND FREE RADICAL DAMAGE IN NEUROLOGY SE Oxidative Stress in Applied Basic Research and Clinical Practice LA English DT Article; Book Chapter DE Cyclooxygenase; Arachidonic acid; Inflammation; Excitotoxicity; Nonsteroidal antiinflammatory drugs; Alzheimer's disease; Prostaglandins ID NONSTEROIDAL ANTIINFLAMMATORY DRUGS; INDUCED OXIDATIVE DAMAGE; PASSIVE-AVOIDANCE TASK; CENTRAL-NERVOUS-SYSTEM; NEURONAL CELL-DEATH; BARRIER IN-VITRO; ALZHEIMERS-DISEASE; PARKINSONS-DISEASE; RAT HIPPOCAMPUS; INDUCIBLE CYCLOOXYGENASE AB The cyclooxygenases COX-1 and COX-2 metabolize arachidonic acid to prostaglandins (PGs) and thromboxanes and are thought to play a role in neuroinflammation and excitotoxicity, which are important components in the progression of neurodegenerative diseases. However, the exact role of each isoform in these processes remains unclear. This chapter reviews preclinical and clinical data on COX-1 and COX-2 inhibition in the neuroinflammatory and excitotoxic processes. Potential implications for clinical use in patients suffering from neurodegenerative disorders with a marked inflammatory component, such as Alzheimer's disease, are discussed. C1 [Bosetti, Francesca] NIA, Brain Physiol & Metab Sect, NIH, Bethesda, MD 20892 USA. RP Bosetti, F (reprint author), NIA, Brain Physiol & Metab Sect, NIH, Bethesda, MD 20892 USA. EM frances@mail.nih.gov NR 121 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013, UNITED STATES SN 2197-7224 BN 978-1-60327-513-2 J9 OXID STRESS APPL BAS JI Oxid. Stress Appl. Basic Res. Clin. Pract. PY 2011 BP 119 EP 136 DI 10.1007/978-1-60327-514-9_8 D2 10.1007/978-1-60327-514-9 PG 18 WC Biochemical Research Methods; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA BSM94 UT WOS:000284978600008 ER PT J AU Grobman, WA Lai, YL Landon, MB Spong, CY Rouse, DJ Varner, MW Caritis, SN Harper, M Wapner, RJ Sorokin, Y AF Grobman, William A. Lai, Yinglei Landon, Mark B. Spong, Catherine Y. Rouse, Dwight J. Varner, Michael W. Caritis, Steve N. Harper, Margaret Wapner, Ronald J. Sorokin, Yoram CA Eunice Kennedy Shriver Natl Inst C TI The change in the rate of vaginal birth after caesarean section SO PAEDIATRIC AND PERINATAL EPIDEMIOLOGY LA English DT Article DE prior caesarean section; trial of birth; time trend; vaginal birth after caesarean ID DELIVERY; TRIAL; LABOR; TRENDS; RISK AB P>Grobman WA, Lai Y, Landon MB, Spong CY, Rouse DJ, Varner MW, Caritis SN, Harper M, Wapner RJ, Sorokin Y. The change in the rate of vaginal birth after caesarean section. Paediatric and Perinatal Epidemiology 2010. The objective of this study was to determine whether, and to what degree, the change in the vaginal birth after caesarean section (VBAC) rate is due to a change in the characteristics of the obstetric population, the undertaking of a trial of labour (TOL), or the tendency to abandon a TOL once it has been initiated. All women with one prior low transverse caesarean section (CS) and a vertex singleton gestation at term were identified in a registry of CS deliveries occurring at eight academic centres during a 4-year period (1999-2002). Women were classified by their predicted chance of VBAC and year-to-year differences were analysed. Of the 9643 women who met criteria for analysis, 5334 (55.3%) underwent a TOL. From 1999 to 2002, the VBAC rate underwent a steady decline: 51.8% to 45.1% to 37.4% to 29.8% (P < 0.001). Although there were some changes in the characteristics of the population that predispose to successful VBAC, as well as some reduction in the chance that a VBAC is successful once a TOL is undertaken, the most pervasive reason for this decline was that women became increasingly likely to forego a TOL, regardless of their likelihood of vaginal delivery. Based on these results, it appears that the change over time in the VBAC rate is multifactorial, although the greatest change has been a decrease in the frequency with which women undertake a TOL, and this change is observed in all categories of the chance of a successful TOL. C1 [Grobman, William A.] Northwestern Univ, Dept Obstet, Chicago, IL 60611 USA. [Grobman, William A.] Northwestern Univ, Dept Gynecol, Chicago, IL 60611 USA. [Landon, Mark B.] Ohio State Univ, Columbus, OH 43210 USA. [Rouse, Dwight J.] Univ Alabama, Birmingham, AL USA. [Varner, Michael W.] Univ Utah, Salt Lake City, UT USA. [Caritis, Steve N.] Univ Pittsburgh, Pittsburgh, PA USA. [Harper, Margaret] Wake Forest Univ Hlth Sci, Winston Salem, NC USA. [Wapner, Ronald J.] Thomas Jefferson Univ, Philadelphia, PA 19107 USA. [Sorokin, Yoram] Wayne State Univ, Detroit, MI USA. [Spong, Catherine Y.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Bethesda, MD USA. [Lai, Yinglei] George Washington Univ, Ctr Biostat, Washington, DC USA. RP Grobman, WA (reprint author), 250 E Super St,Suite 05-2175, Chicago, IL 60611 USA. EM w-grobman@northwestern.edu RI Varner, Michael/K-9890-2013 OI caritis, steve/0000-0002-2169-0712; Varner, Michael/0000-0001-9455-3973 FU Eunice Kennedy Shriver National Institute of Child Health and Human Development [HD21410, HD27860, HD27869, HD27915, HD27917, HD34116, HD34136, HD34208, HD40512, HD36801] FX Supported by grants from the Eunice Kennedy Shriver National Institute of Child Health and Human Development (HD21410, HD27860, HD27869, HD27915, HD27917, HD34116, HD34136, HD34208, HD40512 and HD36801). NR 13 TC 14 Z9 15 U1 0 U2 4 PU WILEY-BLACKWELL PUBLISHING, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0269-5022 J9 PAEDIATR PERINAT EP JI Paediatr. Perinat. Epidemiol. PD JAN PY 2011 VL 25 IS 1 BP 37 EP 43 DI 10.1111/j.1365-3016.2010.01169.x PG 7 WC Public, Environmental & Occupational Health; Obstetrics & Gynecology; Pediatrics SC Public, Environmental & Occupational Health; Obstetrics & Gynecology; Pediatrics GA 691FO UT WOS:000285065900005 PM 21133967 ER PT J AU Yang, PF Chen, DY Hu, JW Chen, JH Yen, CT AF Yang, Pai-Feng Chen, Der-Yow Hu, James W. Chen, Jyh-Horng Yen, Chen-Tung TI Functional tracing of medial nociceptive pathways using activity-dependent manganese-enhanced MRI SO PAIN LA English DT Article DE Cingulate cortex; Intralaminar nuclei; Medial dorsal nucleus; Pain; Rat; Thalamus ID ANTERIOR CINGULATE CORTEX; RESONANCE-IMAGING MEMRI; POSITRON-EMISSION-TOMOGRAPHY; MEDULLARY DORSAL-HORN; CIRCUITS IN-VIVO; THALAMIC NUCLEI; BASAL GANGLIA; CENTRAL SENSITIZATION; RESPONSE PROPERTIES; NEURONAL RESPONSES AB Manganese ion (Mn(2+)) was used as a paramagnetic contrast agent in T1-weighted magnetic resonance imaging (MRI) images. They enter neural cells though voltage-gated calcium channels and are activity-dependently transported along axons and across synapses. The aim of the present study was to investigate the nociceptive medial thalamus projection in rats by activity-dependent manganese-enhanced magnetic resonance imaging (MEMRI). Rats under urethane and a-chloralose anesthesia were microinjected with manganese chloride (MnCl(2), 120 mmol/L, iontophoretically with a 5-mu A current for 15 min) into the right medial thalamus. Innocuous (at a 50-mu A intensity for 0.2 ms) or noxious (at a 5-mA intensity for 2 ms) electrical stimuli were applied through a pair of needles in the left forepaw pads once every 6 s for 5 h. Enhanced transport of Mn(2+) were found in the anterior cingulate cortex, midcingulate cortex, retrosplenial cortex, ventral medial caudate-putamen, nucleus accumbens, and amygdala in the noxious-stimulated group. Enhancements in the anterior cingulate cortex, midcingulate cortex, ventral medial caudate-putamen, nucleus accumbens, and amygdala, but not the retrosplenial cortex, were attenuated by an intraperitoneal injection of morphine (5 mg/kg and 1 mg/kg/h, intraperitoneal). These results indicate that a combination of MEMRI with activity-induced manganese-dependent contrast is useful for delineating functional connections in the pain pathway. (C) 2010 International Association for the Study of Pain. Published by Elsevier B. V. All rights reserved. C1 [Hu, James W.; Chen, Jyh-Horng; Yen, Chen-Tung] Natl Taiwan Univ, Inst Zool, Taipei 10617, Taiwan. [Chen, Der-Yow] Natl Inst Neurol Disorders & Stroke, Lab Funct & Mol Imaging, NIH, Bethesda, MD 20892 USA. [Yang, Pai-Feng; Chen, Jyh-Horng] Natl Taiwan Univ, Interdisciplinary MRI MRI Lab, Dept Elect Engn, Taipei 10617, Taiwan. [Hu, James W.] Univ Toronto, Fac Dent, Toronto, ON M5G 1G6, Canada. [Chen, Jyh-Horng; Yen, Chen-Tung] Natl Taiwan Univ, Neurobiol & Cognit Sci Ctr, Taipei 10617, Taiwan. RP Chen, JH (reprint author), Natl Taiwan Univ, Inst Zool, 1 Roosevelt Rd,Sec 4, Taipei 10617, Taiwan. EM jhchen@ntu.edu.tw; ctyen@ntu.edu.tw RI Yen, Chen-Tung/F-5302-2011 OI Yen, Chen-Tung/0000-0002-0076-4487 FU National Science Council of Taiwan [NSC95-2311-B002-017-MY3] FX We thank the interdisciplinary MRI/MRS laboratory and C. H. Hsieh of Instrumentation Center, National Taiwan University, for MRI experiments. This study was supported by the National Science Council of Taiwan (NSC95-2311-B002-017-MY3). NR 72 TC 18 Z9 19 U1 0 U2 6 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0304-3959 J9 PAIN JI Pain PD JAN PY 2011 VL 152 IS 1 BP 194 EP 203 DI 10.1016/j.pain.2010.10.027 PG 10 WC Anesthesiology; Clinical Neurology; Neurosciences SC Anesthesiology; Neurosciences & Neurology GA 695ZD UT WOS:000285410800031 PM 21122994 ER PT J AU Kerlikowske, G Jones, CM LaBelle, RM Condon, TP AF Kerlikowske, Gil Jones, Christopher M. LaBelle, Regina M. Condon, Timothy P. TI Prescription Drug Monitoring Programs-Lack of Effectiveness or a Call to Action? SO PAIN MEDICINE LA English DT Editorial Material ID NONMEDICAL USE C1 [Jones, Christopher M.] US Dept HHS, US FDA, Washington, DC 20201 USA. [Condon, Timothy P.] US Dept HHS, NIDA, Washington, DC 20201 USA. NR 13 TC 4 Z9 4 U1 0 U2 1 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1526-2375 J9 PAIN MED JI Pain Med. PY 2011 VL 12 IS 5 BP 687 EP 689 DI 10.1111/j.1526-4637.2011.01108.x PG 3 WC Medicine, General & Internal SC General & Internal Medicine GA 762OM UT WOS:000290489300001 PM 21481174 ER PT J AU Smith, WR Ballas, SK McCarthy, WF Bauserman, RL Swerdlow, PS Steinberg, MH Waclawiw, MA AF Smith, Wally R. Ballas, Samir K. McCarthy, William F. Bauserman, Robert L. Swerdlow, Paul S. Steinberg, Martin H. Waclawiw, Myron A. CA Investigators Multictr Study Hydro TI The Association Between Hydroxyurea Treatment and Pain Intensity, Analgesic Use, and Utilization in Ambulatory Sickle Cell Anemia Patients SO PAIN MEDICINE LA English DT Article DE Analgesic; Chronic Pain; Pain Management; Outcome Assessment; Randomized Controlled Trial ID FETAL HEMOGLOBIN; BABY HUG; HOME MANAGEMENT; RISK-FACTORS; DAILY DIARY; DISEASE; CHILDREN; ADOLESCENTS; TRIAL; MULTICENTER AB Background. We compared daily pain, home analgesic use, and utilization among ambulatory adults in the randomized Multicenter Study of Hydroxyurea in Sickle Cell Anemia (MSH). We related the fetal hemoglobin (HbF) hydroxyurea response to these response variables. Methods. Patients rated their sickle cell pain intensity (0-9), use of analgesics, and visits for pain daily. Diaries were collected biweekly, and intensity was collapsed into single interval ratings. The interval proportions of days of analgesic use and medical visits for pain were also calculated. Group comparisons were made by intention to treat as well as by HbF change levels from baseline to 2 years of treatment (placebo and low, medium, high, or very high response). Results. A total of 134 (44.8%) enrollees completed 2 years of follow-up. Pain intensity correlated with analgesic use (r = 0.83, P > 0.0001) and utilization (r = 0.50, P < 0.0001). Pain intensity was lower for patients on hydroxyurea (2.51 +/- 0.062 vs 2.82 +/- 0.063 placebo, F(1,270) = 11.65, P = 0.0007). The difference, though small, appeared early and was sustained. Analgesic use and utilization were also slightly lower (analgesic use: F(1,270) = 11.97, P = 0.0006; utilization: F(1,270) = 32.0, P < 0.0001). Each was statistically significantly lower among hydroxyurea patients with higher HbF treatment responses to hydroxyurea. Conclusions. Hydroxyurea usage led to a small, statistically significant reduction in daily pain, analgesic use, and utilization in adults in MSH, corroborating previously shown larger reductions in crises and mortality. The degree of daily symptomatic reduction was related to the size of the HbF treatment response, further confirming HbF response as a useful laboratory correlate. C1 [Smith, Wally R.] Virginia Commonwealth Univ, Div Qual Hlth Care, Richmond, VA 23060 USA. [Ballas, Samir K.] Thomas Jefferson Univ, Dept Med, Cardeza Fdn, Philadelphia, PA 19107 USA. [McCarthy, William F.] Maryland Med Res Inst, Baltimore, MD USA. [Swerdlow, Paul S.] Karmanos Canc Inst, Div Hematol Oncol, Detroit, MI USA. [Steinberg, Martin H.] Boston Univ, Ctr Excellence Sickle Cell Dis, Boston, MA 02215 USA. [Waclawiw, Myron A.] NHLBI, Bethesda, MD USA. RP Smith, WR (reprint author), Virginia Commonwealth Univ, Div Qual Hlth Care, Box 980306, Richmond, VA 23060 USA. EM wrsmith@vcu.edu OI Steinberg, Martin/0000-0001-8800-8020 FU National Heart, Lung, and Blood Institute [NO1-HB-67129] FX This study was supported by National Heart, Lung, and Blood Institute contract NO1-HB-67129. NR 38 TC 7 Z9 7 U1 1 U2 2 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1526-2375 J9 PAIN MED JI Pain Med. PY 2011 VL 12 IS 5 BP 697 EP 705 DI 10.1111/j.1526-4637.2011.01096.x PG 9 WC Medicine, General & Internal SC General & Internal Medicine GA 762OM UT WOS:000290489300005 PM 21481164 ER PT J AU Murphy, PM Murphy, CA AF Murphy, Philip M. Murphy, Carolyn A. TI Hyperventilation as a Simple Cure for Severe Exercise-Associated Muscle Cramping SO PAIN MEDICINE LA English DT Letter C1 [Murphy, Philip M.] NIAID, NIH, Lab Mol Immunol, Mol Signaling Sect, Bethesda, MD 20892 USA. [Murphy, Carolyn A.] Harvard Univ, Sch Med, Brookline, MA USA. RP Murphy, PM (reprint author), NIAID, NIH, Lab Mol Immunol, Mol Signaling Sect, 9000 Rockville Pike, Bethesda, MD 20892 USA. FU Intramural NIH HHS NR 4 TC 2 Z9 2 U1 0 U2 2 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1526-2375 J9 PAIN MED JI Pain Med. PY 2011 VL 12 IS 6 BP 987 EP 987 DI 10.1111/j.1526-4637.2011.01112.x PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA 791GO UT WOS:000292653300017 PM 21539699 ER PT J AU Reid, MC Bennett, DA Chen, WG Eldadah, BA Farrar, JT Ferrell, B Gallagher, RM Hanlon, JT Herr, K Horn, SD Inturrisi, CE Lemtouni, S Lin, YW Michaud, K Morrison, RS Neogi, T Porter, LL Solomon, DH Von Korff, M Weiss, K Witter, J Zacharoff, KL AF Reid, M. Cary Bennett, David A. Chen, Wen G. Eldadah, Basil A. Farrar, John T. Ferrell, Bruce Gallagher, Rollin M. Hanlon, Joseph T. Herr, Keela Horn, Susan D. Inturrisi, Charles E. Lemtouni, Salma Lin, Yu Woody Michaud, Kaleb Morrison, R. Sean Neogi, Tuhina Porter, Linda L. Solomon, Daniel H. Von Korff, Michael Weiss, Karen Witter, James Zacharoff, Kevin L. TI Improving the Pharmacologic Management of Pain in Older Adults: Identifying the Research Gaps and Methods to Address Them SO PAIN MEDICINE LA English DT Review DE Analgesic Use; Chronic Noncancer Pain; Older Adults ID CHRONIC NONCANCER PAIN; NONSTEROIDAL ANTIINFLAMMATORY DRUGS; OBSTRUCTIVE PULMONARY-DISEASE; PERSISTENT NONMALIGNANT PAIN; NURSING-HOME RESIDENTS; NATIONAL-DATA-BANK; MUSCULOSKELETAL PAIN; UNITED-STATES; COGNITIVE IMPAIRMENT; RHEUMATIC-DISEASES AB Objective. There has been a growing recognition of the need for better pharmacologic management of chronic pain among older adults. To address this need, the National Institutes of Health Pain Consortium sponsored an "Expert Panel Discussion on the Pharmacological Management of Chronic Pain in Older Adults" conference in September 2010 to identify research gaps and strategies to address them. Specific emphasis was placed on ascertaining gaps regarding use of opioid and nonsteroidal anti-inflammatory medications because of continued uncertainties regarding their risks and benefits. Design. Eighteen panel members provided oral presentations; each was followed by a multidisciplinary panel discussion. Meeting transcripts and panelists' slide presentations were reviewed to identify the gaps and the types of studies and research methods panelists suggested could best address them. Results. Fifteen gaps were identified in the areas of treatment (e.g., uncertainty regarding the long-term safety and efficacy of commonly prescribed analgesics), epidemiology (e.g., lack of knowledge regarding the course of common pain syndromes), and implementation (e.g., limited understanding of optimal strategies to translate evidence-based pain treatments into practice). Analyses of data from electronic health care databases, observational cohort studies, and ongoing cohort studies (augmented with pain and other relevant outcomes measures) were felt to be practical methods for building an age-appropriate evidence base to improve the pharmacologic management of pain in later life. Conclusion. Addressing the gaps presented in the current report was judged by the panel to have substantial potential to improve the health and wellbeing of older adults with chronic pain. C1 [Reid, M. Cary] Weill Cornell Med Ctr, Div Geriatr & Gerontol, New York, NY 10065 USA. [Bennett, David A.] Rush Univ, Med Ctr, Dept Neurol Sci, Rush Alzheimers Dis Ctr, Chicago, IL 60612 USA. [Chen, Wen G.] NIA, Behav & Syst Neurosci Branch, Div Neurosci, Bethesda, MD 20892 USA. [Eldadah, Basil A.] NIA, Div Geriatr & Clin Gerontol, Bethesda, MD 20892 USA. [Farrar, John T.] Univ Penn, Dept Epidemiol, Philadelphia, PA 19104 USA. [Farrar, John T.] Univ Penn, Dept Neurol, Philadelphia, PA 19104 USA. [Ferrell, Bruce] UCLA Sch Med, Div Geriatr, Los Angeles, CA USA. Univ Penn, Sch Med, Philadelphia VA Med Ctr, Penn Pain Med Ctr, Philadelphia, PA 19104 USA. Univ Penn, Sch Med, Dept Psychiat, Philadelphia, PA 19104 USA. Univ Penn, Sch Med, Dept Anesthesiol & Crit Care, Philadelphia, PA 19104 USA. [Gallagher, Rollin M.] Univ Pittsburgh, Dept Geriatr Med, Pittsburgh, PA USA. [Hanlon, Joseph T.] VA Pittsburgh Hlth Syst, Geriatr Res Educ & Clin Ctr, Pittsburgh, PA USA. [Herr, Keela] Univ Iowa, Coll Nursing, John A Hartford Ctr Geriatr Nursing Excellence, Iowa City, IA 52242 USA. [Horn, Susan D.] Inst Clin Outcomes Res, Salt Lake City, UT USA. [Inturrisi, Charles E.] Weill Cornell Med Coll, Dept Pharmacol, New York, NY USA. [Lemtouni, Salma; Weiss, Karen] US FDA, Ctr Drug Evaluat & Res, Washington, DC 20204 USA. [Lin, Yu Woody] Natl Inst Drug Abuse, Div Clin Neurosci & Behav Res, Bethesda, MD USA. [Michaud, Kaleb] Univ Nebraska Med Ctr, Omaha, NE USA. [Michaud, Kaleb] Natl Data Bank Rheumat Dis, Wichita, KS USA. [Morrison, R. Sean] Mt Sinai Sch Med, Brookdale Dept Geriatr & Palliat Med, New York, NY USA. [Neogi, Tuhina] Boston Univ, Sch Med, Sect Clin Epidemiol Res & Training Unit, Boston, MA 02118 USA. [Neogi, Tuhina] Boston Univ, Sch Med, Rheumatol Sect, Boston, MA 02118 USA. [Porter, Linda L.] Natl Inst Neurol Disorders & Stroke, Bethesda, MD USA. [Solomon, Daniel H.] Harvard Univ, Brigham & Womens Hosp, Div Pharmacoepidemiol & Pharmacoecon, Sch Med, Boston, MA 02115 USA. [Solomon, Daniel H.] Brigham & Womens Hosp, Div Rheumatol, Boston, MA 02115 USA. [Von Korff, Michael] Ctr Hlth Studies Grp Hlth Cooperat, Seattle, WA USA. [Witter, James] NIAMSD, Div Skin & Rheumat Dis, Bethesda, MD 20892 USA. [Zacharoff, Kevin L.] Inflexxion Inc, Newton, MA USA. RP Reid, MC (reprint author), Weill Cornell Med Ctr, Div Geriatr & Gerontol, 525 E 68th St,Box 39, New York, NY 10065 USA. EM mcr2004@med.cornell.edu RI Inturrisi, Charles/E-7365-2013; OI Reid, Cary/0000-0001-8117-662X; Neogi, Tuhina/0000-0002-9515-1711 FU Edward R. Roybal Center for Translational Research on Aging, NIA [P30 AG22845]; NIA [P30AG10161, R01AG15819, R01AG17917, P30AG028741, K24AG022345, R01AG030141, R01AG034181]; National Center for Research Resources [UL1RR024134]; National Institute of Aging [P30AG024827, T32AG021885, K07AG033174, R01AG034056, R56AG027017, U01AG012553]; National Institute of Mental Health [R34MH082682]; National Institute of Nursing [R01NR010135]; AHRQ [R01HS017695, R01HS018721, K12HS019461]; VA Health Services [IIR-06-062]; National Cancer Institute [R01CA115363]; National Institute of Nursing Research [T32NR011147]; NIDA [RC2DA028928, R01DA022557]; National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS) [RC1AR058601, K23AR055127, K24AR055989] FX The authors would like to acknowledge the participation of all the conference attendees, who are listed in Appendix A. Dr. Reid was supported by an Edward R. Roybal Center for Translational Research on Aging Award (P30 AG22845) provided by the NIA. Dr. Bennett was supported by NIA grants P30AG10161, R01AG15819, and R01AG17917. Dr. Farrar was supported by a grant from the National Center for Research Resources (UL1RR024134). Dr. Hanlon was supported by National Institute of Aging grants (P30AG024827, T32AG021885, K07AG033174, R01AG034056, R56AG027017, U01AG012553), a National Institute of Mental Health grant (R34MH082682), a National Institute of Nursing Research grant (R01NR010135), AHRQ grants (R01HS017695, R01HS018721, K12HS019461), and a VA Health Services Research grant (IIR-06-062). Dr. Herr was supported by grants from the National Cancer Institute (R01CA115363) and National Institute of Nursing Research (T32NR011147). Drs. Horn and Inturrisi were supported by American Recovery and Reinvestment Act (ARRA) grant RC2DA028928 from NIDA. Dr. Michaud was supported by an ARRA grant from the National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS) (RC1AR058601). Dr. Neogi was supported by a grant from the NIAMS (K23AR055127). Dr. Morrison was supported by grants from the NIA (P30AG028741, K24AG022345, and R01AG030141). Dr. Solomon was supported by a grant from the NIAMS (K24AR055989). Dr. Von Korff was supported by grants from the NIDA (R01DA022557) and the NIA (R01AG034181). NR 106 TC 37 Z9 38 U1 7 U2 19 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1526-2375 J9 PAIN MED JI Pain Med. PY 2011 VL 12 IS 9 BP 1336 EP 1357 DI 10.1111/j.1526-4637.2011.01211.x PG 22 WC Medicine, General & Internal SC General & Internal Medicine GA 822MJ UT WOS:000295051500009 PM 21834914 ER PT J AU Marcum, ZA Perera, S Donohue, JM Boudreau, RM Newman, AB Ruby, CM Studenski, SA Kwoh, CK Simonsick, EM Bauer, DC Satterfield, S Hanlon, JT AF Marcum, Zachary A. Perera, Subashan Donohue, Julie M. Boudreau, Robert M. Newman, Anne B. Ruby, Christine M. Studenski, Stephanie A. Kwoh, C. Kent Simonsick, Eleanor M. Bauer, Doug C. Satterfield, Suzanne Hanlon, Joseph T. CA Hlth Aging & Body Composition Stud TI Analgesic Use for Knee and Hip Osteoarthritis in Community-Dwelling Elders SO PAIN MEDICINE LA English DT Article DE Aged; Analgesic; Osteoarthritis ID CARDIOVASCULAR-DISEASE INDICATORS; OLDER-ADULTS; BODY-COMPOSITION; HEALTH ABC; PAIN; CARE; RECOMMENDATIONS; MANAGEMENT; PERFORMANCE; ARTHRITIS AB Objective. To examine the prevalence and correlates of non-opioid and opioid analgesic use and descriptively evaluate potential undertreatment in a sample of community-dwelling elders with symptomatic knee and/or hip osteoarthritis (OA). Design. Cross-sectional. Setting. Health, Aging, and Body Composition Study. Patients. Six hundred and fifty-two participants attending the year 6 visit (2002-03) with symptomatic knee and/or hip OA. Outcome Measures. Analgesic use was defined as taking >= 1 non-opioid and/or >= 1 opioid receptor agonist. Non-opioid and opioid doses were standardized across all agents by dividing the daily dose used by the minimum effective analgesic daily dose. Inadequate pain control was defined as severe/extreme OA pain in the past 30 days from a modified Western Ontario and McMaster Universities Osteoarthritis Index. Results. Just over half (51.4%) reported taking at least one non-opioid analgesic and approximately 10% was taking an opioid, most (88.5%) of whom also took a non-opioid. One in five participants (19.3%) had inadequate pain control, 39% of whom were using <1 standardized daily dose of either a non-opioid or opioid analgesic. In adjusted analyses, severe/extreme OA pain was significantly associated with both non-opioid (adjusted odds ratio [AOR] = 2.44; 95% confidence interval [95% CI] = 1.49-3.99) and opioid (AOR = 2.64; 95% CI = 1.26-5.53) use. Conclusions. Although older adults with severe/extreme knee and/or hip OA pain are more likely to take analgesics than those with less severe pain, a sizable proportion takes less than therapeutic doses and thus may be undertreated. Further research is needed to examine barriers to optimal analgesic use. C1 [Marcum, Zachary A.] Univ Pittsburgh, Sch Med, Dept Med Geriatr, Pittsburgh, PA 15213 USA. [Kwoh, C. Kent] Univ Pittsburgh, Sch Med, Dept Med Rheumatol & Clin Immunol, Pittsburgh, PA 15213 USA. [Perera, Subashan] Univ Pittsburgh, Grad Sch Publ Hlth, Dept Biostat, Pittsburgh, PA 15213 USA. [Donohue, Julie M.] Univ Pittsburgh, Grad Sch Publ Hlth, Dept Hlth Policy & Management, Pittsburgh, PA 15213 USA. [Boudreau, Robert M.; Newman, Anne B.; Hanlon, Joseph T.] Univ Pittsburgh, Grad Sch Publ Hlth, Dept Epidemiol, Pittsburgh, PA 15213 USA. [Ruby, Christine M.; Hanlon, Joseph T.] Univ Pittsburgh, Sch Pharm, Dept Pharm & Therapeut, Pittsburgh, PA 15213 USA. [Studenski, Stephanie A.; Kwoh, C. Kent; Hanlon, Joseph T.] Vet Affairs Pittsburgh Healthcare Syst, Ctr Hlth Equ Res, Pittsburgh, PA USA. [Studenski, Stephanie A.; Kwoh, C. Kent; Hanlon, Joseph T.] Vet Affairs Pittsburgh Healthcare Syst, Geriatr Res Educ & Clin Ctr, Pittsburgh, PA USA. [Simonsick, Eleanor M.] NIA, Intramural Res Program, Baltimore, MD 21224 USA. [Bauer, Doug C.] Univ Calif San Francisco, Sch Med, Dept Med Gen Internal Med, San Francisco, CA USA. [Satterfield, Suzanne] Univ Tennessee, Ctr Hlth Sci, Dept Prevent Med, Memphis, TN 38163 USA. RP Marcum, ZA (reprint author), Univ Pittsburgh, Sch Med, Dept Med Geriatr, Kaufmann Med Bldg,Suite 500,3471 5th Ave, Pittsburgh, PA 15213 USA. EM zam12@pitt.edu RI Perera, Subashan/D-7603-2014; Newman, Anne/C-6408-2013; OI Newman, Anne/0000-0002-0106-1150; Boudreau, Robert/0000-0003-0162-5187; Donohue, Julie/0000-0003-2418-6017 FU National Institute on Aging [R01AG027017, P30AG024827, T32 AG021885, K07AG033174, R01AG034056, N01-AG-6-2101, N01-AG-6-2103, N01-AG-6-2106]; National Institute of Mental Health [R34 MH082682]; National Institute of Nursing Research [R01 NR010135]; Agency for Healthcare Research and Quality [R01 HS017695]; VA Health Services [IIR-06-062]; NIH, National Institute on Aging FX This study was primarily supported by National Institute on Aging grants and contracts (R01AG027017, P30AG024827, T32 AG021885, K07AG033174, R01AG034056, N01-AG-6-2101, N01-AG-6-2103, and N01-AG-6-2106), a National Institute of Mental Health grant (R34 MH082682), a National Institute of Nursing Research grant (R01 NR010135), an Agency for Healthcare Research and Quality grant (R01 HS017695), and a VA Health Services Research grant (IIR-06-062). This research was also supported in part by the Intramural Research program of the NIH, National Institute on Aging. The authors would like to thank Yihuang Kang and Yan Zheng for their assistance with data programming. NR 35 TC 12 Z9 12 U1 1 U2 1 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1526-2375 J9 PAIN MED JI Pain Med. PY 2011 VL 12 IS 11 BP 1628 EP 1636 DI 10.1111/j.1526-4637.2011.01249.x PG 9 WC Medicine, General & Internal SC General & Internal Medicine GA 854PO UT WOS:000297506900009 PM 21992521 ER PT J AU Lansford, JE Bornstein, MH AF Lansford, Jennifer E. Bornstein, Marc H. TI Parenting Attributions and Attitudes in Diverse Cultural Contexts: Introduction to the Special Issue SO PARENTING-SCIENCE AND PRACTICE LA English DT Article ID CHILD-REARING ORIENTATIONS; FAMILY; MOTHERS; SELF; BEHAVIOR; BELIEFS; INDIVIDUALISM; COLLECTIVISM; INSTRUMENTS; PERSONALITY AB This Introduction describes the conceptual rationale, the general methods of the Parenting Across Cultures Project, and the analytic plan adopted in the articles in this special issue. Each article that follows this Introduction describes the parenting context and mothers' and fathers' attributions for successes and failures in caregiving and progressive versus authoritarian childrearing attitudes in each of nine countries: China, Colombia, Italy, Jordan, Kenya, the Philippines, Sweden, Thailand, and the United States. Results in each article address questions of similarities and differences in mothers' and fathers' attributions and attitudes and how highly mothers' attributions and attitudes are correlated with fathers' attributions and attitudes within a national group. The special issue concludes with an article that draws connections among the findings across the nine countries and outlines implications of similarities and differences between mothers' and fathers' parenting attributions and attitudes. C1 [Lansford, Jennifer E.] Duke Univ, Ctr Child & Family Policy, Durham, NC 27708 USA. [Bornstein, Marc H.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Rockville, MD USA. RP Lansford, JE (reprint author), Duke Univ, Ctr Child & Family Policy, Box 90545, Durham, NC 27708 USA. EM lansford@duke.edu NR 85 TC 14 Z9 14 U1 2 U2 19 PU LAWRENCE ERLBAUM ASSOC INC-TAYLOR & FRANCIS PI PHILADELPHIA PA 325 CHESTNUT STREET, STE 800, PHILADELPHIA, PA 19106 USA SN 1529-5192 J9 PARENT-SCI PRACT JI Parent.-Sci. Pract. PY 2011 VL 11 IS 2-3 SI SI BP 87 EP 101 DI 10.1080/15295192.2011.585552 PG 15 WC Family Studies; Psychology, Developmental SC Family Studies; Psychology GA 885KE UT WOS:000299777100001 ER PT J AU Lansford, JE Bornstein, MH Dodge, KA Skinner, AT Putnick, DL Deater-Deckard, K AF Lansford, Jennifer E. Bornstein, Marc H. Dodge, Kenneth A. Skinner, Ann T. Putnick, Diane L. Deater-Deckard, Kirby TI Attributions and Attitudes of Mothers and Fathers in the United States SO PARENTING-SCIENCE AND PRACTICE LA English DT Article ID AFRICAN-AMERICAN; IMMIGRANT FAMILIES; BEHAVIOR PROBLEMS; ACHIEVEMENT; CHILDREN; METAANALYSIS; PERCEPTIONS; ENVIRONMENT; PATTERNS; PARENTS AB Objective. The present study examined mean level similarities and differences as well as correlations between U. S. mothers' and fathers' attributions regarding successes and failures in caregiving situations and progressive versus authoritarian attitudes. Design. Interviews were conducted with mothers and fathers in 139 European American, Latin American, and African American families. Results. Interactions between parent gender and ethnicity emerged for adult-controlled failure and perceived control over failure. Fathers reported higher adult-controlled failure and child-controlled failure attributions than did mothers, whereas mothers reported attitudes that were more progressive and modern than did fathers; these differences remained significant after controlling for parents' age, education, and possible social desirability bias. Ethnic differences emerged for 5 of the 7 attributions and attitudes examined; 4 remained significant after controlling for parents' age, education, and possible social desirability bias. Medium effect sizes were found for concordance between parents in the same family for attributions regarding uncontrollable success, child-controlled failure, progressive attitudes, authoritarian attitudes, and modernity of attitudes after controlling for parents' age, education, and possible social desirability bias. Conclusions. This work elucidates ways that parent gender and ethnicity relate to attributions regarding U. S. parents' successes and failures in caregiving situations and to their progressive versus authoritarian parenting attitudes. C1 [Lansford, Jennifer E.] Duke Univ, Ctr Child & Family Policy, Durham, NC 27708 USA. [Bornstein, Marc H.; Putnick, Diane L.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Rockville, MD USA. [Deater-Deckard, Kirby] Virginia Tech, Blacksburg, VA 24060 USA. RP Lansford, JE (reprint author), Duke Univ, Ctr Child & Family Policy, Box 90545, Durham, NC 27708 USA. EM lansford@duke.edu OI Putnick, Diane/0000-0002-6323-749X FU FIC NIH HHS [R03 TW008141-01, R03 TW008141]; NICHD NIH HHS [R01 HD054805, R01 HD054805-01A1]; NIDA NIH HHS [K05 DA015226-01, K05 DA015226] NR 57 TC 18 Z9 18 U1 0 U2 10 PU LAWRENCE ERLBAUM ASSOC INC-TAYLOR & FRANCIS PI PHILADELPHIA PA 325 CHESTNUT STREET, STE 800, PHILADELPHIA, PA 19106 USA SN 1529-5192 J9 PARENT-SCI PRACT JI Parent.-Sci. Pract. PY 2011 VL 11 IS 2-3 SI SI BP 199 EP 213 DI 10.1080/15295192.2011.585567 PG 15 WC Family Studies; Psychology, Developmental SC Family Studies; Psychology GA 885KE UT WOS:000299777100010 PM 21822402 ER PT J AU Bornstein, MH Putnick, DL Lansford, JE AF Bornstein, Marc H. Putnick, Diane L. Lansford, Jennifer E. TI Parenting Attributions and Attitudes in Cross-Cultural Perspective SO PARENTING-SCIENCE AND PRACTICE LA English DT Article ID CHILD-REARING ORIENTATIONS; YOUNG-CHILDREN; BEHAVIOR; SELF; ACHIEVEMENT; AGREEMENT; MOTHERS; FAMILY; STYLE; METAANALYSIS AB Objective. This article used the Parenting Across Cultures Project to evaluate similarities and differences in mean levels and relative agreement between mothers' and fathers' attributions and attitudes in parenting in 9 countries. Design. Mothers and fathers reported their perceptions of causes of successes and failures in caregiving and their progressive versus authoritarian childrearing attitudes. Gender and cultural similarities and differences in parents' attributions and attitudes in 9 countries were analyzed: China, Colombia, Italy, Jordan, Kenya, the Philippines, Sweden, Thailand, and the United States. Results. Although mothers and fathers did not differ in any attribution, mothers reported more progressive parenting attitudes and modernity of childrearing attitudes than did fathers, and fathers reported more authoritarian attitudes than did mothers. Country differences also emerged in all attributions and attitudes that were examined. Mothers' and fathers' attributions and their attitudes were moderately correlated, but parenting attitudes were more highly correlated in parents than were attributions. Conclusions. We draw connections among the findings across the 9 countries and outline implications for understanding similarities and differences in mothers' and fathers' parenting attributions and attitudes. C1 [Bornstein, Marc H.; Putnick, Diane L.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Bethesda, MD 20892 USA. [Lansford, Jennifer E.] Duke Univ, Durham, NC 27706 USA. RP Bornstein, MH (reprint author), Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Suite 8030,6705 Rockledge Dr, Bethesda, MD 20892 USA. EM marc_h_bornstein@nih.gov OI Putnick, Diane/0000-0002-6323-749X FU FIC NIH HHS [R03 TW008141, R03 TW008141-01]; NICHD NIH HHS [R01 HD054805, R01 HD054805-01A1] NR 85 TC 14 Z9 14 U1 4 U2 27 PU LAWRENCE ERLBAUM ASSOC INC-TAYLOR & FRANCIS PI PHILADELPHIA PA 325 CHESTNUT STREET, STE 800, PHILADELPHIA, PA 19106 USA SN 1529-5192 J9 PARENT-SCI PRACT JI Parent.-Sci. Pract. PY 2011 VL 11 IS 2-3 SI SI BP 214 EP 237 DI 10.1080/15295192.2011.585568 PG 24 WC Family Studies; Psychology, Developmental SC Family Studies; Psychology GA 885KE UT WOS:000299777100011 PM 21927591 ER PT J AU Flood, PM Qian, L Peterson, LJ Zhang, F Shi, JS Gao, HM Hong, JS AF Flood, Patrick M. Qian, Li Peterson, Lynda J. Zhang, Feng Shi, Jing-Shan Gao, Hui-Ming Hong, Jau-Shyong TI Transcriptional Factor NF-kappa B as a Target for Therapy in Parkinson's Disease SO PARKINSONS DISEASE LA English DT Review AB Parkinson's disease (PD) is a neurodegenerative condition characterized by chronic inflammation. Nuclear factor kappa B (NF-kappa B) is a family of inducible transcription factors that are expressed in a wide variety of cells and tissues, including microglia, astrocytes, and neurons, and the classical NF-kappa B pathway plays a key role in the activation and regulation of inflammatory mediator production during inflammation. Activation of the classical NF-kappa B pathway is mediated through the activity of the IKK kinase complex, which consists of a heterotrimer of IKK alpha, IKK beta, and IKK gamma subunits. Targeting NF-kappa B has been proposed as an approach to the treatment of acute and chronic inflammatory conditions, and the use of inhibitors specific for either IKK beta or IKK gamma has now been found to inhibit neurodegeneration of TH+ DA-producing neurons in murine and primate models of Parkinson's disease. These studies suggest that targeting the classical pathway of NF-kappa B through the inhibition of the IKK complex can serve as a useful therapeutic approach to the treatment of PD. C1 [Flood, Patrick M.; Qian, Li; Peterson, Lynda J.] Univ N Carolina, Dept Periodontol & Comprehens Ctr Inflammatory Di, Chapel Hill, NC 27599 USA. [Zhang, Feng; Shi, Jing-Shan] Zunji Med Coll, Dept Pharmacol, Zunji, Peoples R China. [Zhang, Feng; Shi, Jing-Shan] Zunji Med Coll, Key Lab Pharmacol Guizhou, Zunji, Peoples R China. [Zhang, Feng; Gao, Hui-Ming; Hong, Jau-Shyong] NIEHS, Neuropharmacol Sect, Lab Toxicol & Pharmacol, NIH, Res Triangle Pk, NC 27709 USA. RP Flood, PM (reprint author), Univ N Carolina, Dept Periodontol & Comprehens Ctr Inflammatory Di, Chapel Hill, NC 27599 USA. EM pat_flood@dentistry.unc.edu NR 104 TC 6 Z9 6 U1 0 U2 2 PU HINDAWI PUBLISHING CORPORATION PI NEW YORK PA 410 PARK AVENUE, 15TH FLOOR, #287 PMB, NEW YORK, NY 10022 USA SN 2090-8083 J9 PARKINSONS DIS-US JI Parkinsons Dis. PY 2011 AR UNSP 216298 DI 10.4061/2011/216298 PG 8 WC Clinical Neurology SC Neurosciences & Neurology GA V29RN UT WOS:000208765600014 ER PT J AU Imai, Y Venderova, K Park, DS Cai, HB Schmidt, E AF Imai, Yuzuru Venderova, Katerina Park, David S. Cai, Huaibin Schmidt, Enrico TI Animal Models of Parkinson's Disease SO PARKINSONS DISEASE LA English DT Editorial Material C1 [Imai, Yuzuru] Juntendo Univ, Grad Sch Med, Dept Neurosci Neurodegenerat Disorders, Tokyo 1138421, Japan. [Venderova, Katerina] Univ Pacific, Dept Physiol & Pharmacol, Thomas J Long Sch Pharm & Hlth Sci, Stockton, CA 95211 USA. [Park, David S.] Ottawa Hlth Res Inst, Neurosci Res Inst, Ottawa, ON K1H 8M5, Canada. [Cai, Huaibin] NIA, Neurogenet Lab, NIH, Bethesda, MD 20892 USA. [Schmidt, Enrico] Univ Freiburg, Dept Bioinformat & Mol Genet, D-79104 Freiburg, Germany. [Schmidt, Enrico] Univ Freiburg, Ctr Biol Syst Anal, D-79104 Freiburg, Germany. RP Imai, Y (reprint author), Juntendo Univ, Grad Sch Med, Dept Neurosci Neurodegenerat Disorders, Tokyo 1138421, Japan. EM yzimai@juntendo.ac.jp NR 0 TC 1 Z9 1 U1 0 U2 0 PU HINDAWI PUBLISHING CORPORATION PI NEW YORK PA 410 PARK AVENUE, 15TH FLOOR, #287 PMB, NEW YORK, NY 10022 USA SN 2090-8083 J9 PARKINSONS DIS-US JI Parkinsons Dis. PY 2011 AR UNSP 364328 DI 10.4061/2011/364328 PG 2 WC Clinical Neurology SC Neurosciences & Neurology GA V29RN UT WOS:000208765600029 ER PT J AU Leong, ASY Zhuang, ZP AF Leong, Anthony S. -Y. Zhuang, Zhengping TI The Changing Role of Pathology in Breast Cancer Diagnosis and Treatment SO PATHOBIOLOGY LA English DT Article DE Breast cancer; Immunohistochemistry; Molecular technology; Biomarkers; Prognosis; Predictive markers; Proteomics; Drug discovery; Stem cells ID COMPARATIVE GENOMIC HYBRIDIZATION; CARCINOMA IN-SITU; ESTROGEN-RECEPTOR STATUS; COPY-NUMBER CHANGES; GENE-EXPRESSION DATA; QUANTITATIVE RT-PCR; BASAL-LIKE SUBTYPE; DUCTAL CARCINOMA; STEM-CELLS; PROTEIN EXPRESSION AB Pathological examination has been the gold standard for diagnosis in cancer and its role has also included the elucidation of etiology, pathogenesis, clinicopathological correlation, and prognostication. The advent of newer technologies and the realization that breast cancer is heterogeneous has shifted the focus to prognostication, with increased attention being paid to the identification of morphological features and immunohistochemical markers of prognostic relevance. However, despite the massive efforts invested in the identification of immunohistochemical biomarkers in breast cancer the majority have not proven to be of value in multivariate analyses and only estrogen receptor, progesterone receptor, and Her2/neu expression have remained essential components of pathological examination. These 3 markers were initially employed for prognostication but their role in treatment also rendered them of predictive value. Newer molecular methods, especially high-throughput technologies, have shown that even morphologically similar subtypes of breast cancer can show molecular heterogeneity; moreover, infiltrating ductal carcinoma can be separated into at least 4 molecular subtypes designated luminal (ER+, PR+, and Her2/neu-), Her2 overexpressing (ER-, PR-, and Her2/neu+), basal-like (ER-, PR-, Her2/neu-, and CK5/6+, EGFR+), and normal breast-like (ER-, PR-, and Her2/neu-), each with different clinical outcomes. The importance of proliferative gene expression in these subtypes has been demonstrated and surrogate immunohistochemical markers include ER, PR, Her2/neu, and Ki67 for the more expensive molecular tests. Molecular technologies, importantly, have not only provided further insights into the heterogeneity of breast cancer but have also opened new avenues for treatment through the identification of signaling molecules important in the proliferation and survival of the neoplastic cells. The treatment of cancer thus shifts from the conventional approach of 'one size fits all' to one of personalized treatment tailored to the specific characteristics of the tumor. Pathologists continue to play their traditional role in diagnosis but, as purveyors of the excised tissue, pathologists now have the additional role of identifying biomarkers responsive to therapeutic manipulation, thus playing an inextricable role as diagnostic oncologists in the management of breast cancer. Copyright (C) 2011 S. Karger AG, Basel C1 [Leong, Anthony S. -Y.] Univ Newcastle, Hunter Area Pathol Serv, HRMC, Newcastle, NSW 2310, Australia. [Zhuang, Zhengping] NIH, Mol Pathogenesis Unit, Bethesda, MD 20892 USA. RP Leong, ASY (reprint author), Univ Newcastle, Hunter Area Pathol Serv, HRMC, Locked Bag 1, Newcastle, NSW 2310, Australia. EM aleong@mail.newcastle.edu.au NR 169 TC 32 Z9 36 U1 1 U2 9 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 1015-2008 J9 PATHOBIOLOGY JI Pathobiology PY 2011 VL 78 IS 2 BP 99 EP 114 DI 10.1159/000292644 PG 16 WC Cell Biology; Pathology SC Cell Biology; Pathology GA 778TR UT WOS:000291729700005 PM 21677473 ER PT S AU Kino, T Chrousos, GP AF Kino, Tomoshige Chrousos, George P. BE Ghizzoni, L Cappa, M Chrousos, G Loche, S Maghnie, M TI Circadian CLOCK-Mediated Regulation of Target-Tissue Sensitivity to Glucocorticoids: Implications for Cardiometabolic Diseases SO PEDIATRIC ADRENAL DISEASES SE Endocrine Development LA English DT Proceedings Paper CT Pediatric Adrenal Diseases Workshop CT 2nd International Shallow-Water Acoustics Conference CY MAY 16-18, 2010 CY SEP 16-20, 2009 CL Turin, ITALY CL Shanghai, PEOPLES R CHINA SP Off Naval Res, Chinese Acad Sci, Acoust Soc China, Acoust Soc Amer, Natl Nat Sci Fdn China ID PITUITARY-ADRENAL AXIS; METABOLIC SYNDROME; SOMATIC DISORDERS; DNA-BINDING; RECEPTOR; TRANSCRIPTION; COMPLEX; STRESS; EXPRESSION; CROSSTALK AB Glucocorticoids, the end-products of the hypothalamic-pituitary-adrenal (HPA) axis, influence the functions of virtually all organs and tissues through the nuclear glucocorticoid receptor (GR). Circulating levels of glucocorticoids fluctuate naturally in a circadian fashion under the strong influence of the hypothalamic suprachiasmatic nucleus (SCN) circadian CLOCK system, and regulate the transcriptional activity of the GR in the brain and peripheral target tissues. We recently reported that the basic helix-loop-helix transcription factor Clock, which is a histone acetyltransferase and a central component of the self-oscillating transcription factor loop that generates circadian rhythms, represses GR transcriptional activity by acetylating lysine residues within the lysine cluster' located in the hinge region of the receptor. This Clock-mediated repression of GR transcriptional activity oscillates in inverse phase to the HPA axis, acting as a target tissue counter-regulatory mechanism to the diurnally fluctuating circulating glucocorticoids. Interestingly, mild evening elevations of cortisol, as occurs in chronic stress situations, and frequent uncoupling of the SCN CLOCK-directed HPA axis from the daily oscillation of target tissue sensitivity to glucocorticoids, as happens in trans-time zone travel and night shift work, produce functional hypercortisolism and, hence, multiple components of the metabolic syndrome with resultant cardiovascular complications. Copyright (C) 2011 S. Karger AG, Basel C1 [Kino, Tomoshige] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Unit Mol Hormone Act, Program Reprod & Adult Endocrinol, NIH, Bethesda, MD USA. RP Chrousos, GP (reprint author), Univ Athens, Sch Med, Aghia Sohia Childrens Hosp, Dept Pediat 1, GR-11527 Athens, Greece. EM chrousge@med.uoa.gr FU Intramural NIH HHS [ZIA HD008732-09] NR 46 TC 24 Z9 24 U1 0 U2 5 PU KARGER PI BASEL PA POSTFACH, CH-4009 BASEL, SWITZERLAND SN 1421-7082 BN 978-3-8055-9643-5 J9 ENDOCR DEV JI Endocr. Dev. PY 2011 VL 20 BP 116 EP 126 PG 11 WC Endocrinology & Metabolism; Pediatrics SC Endocrinology & Metabolism; Pediatrics GA BTJ75 UT WOS:000287122700012 PM 21164265 ER PT S AU Lui, JC Baron, J AF Lui, Julian C. Baron, Jeffrey BE Ghizzoni, L Cappa, M Chrousos, G Loche, S Maghnie, M TI Effects of Glucocorticoids on the Growth Plate SO PEDIATRIC ADRENAL DISEASES SE Endocrine Development LA English DT Proceedings Paper CT Pediatric Adrenal Diseases Workshop CT 2nd International Shallow-Water Acoustics Conference CY MAY 16-18, 2010 CY SEP 16-20, 2009 CL Turin, ITALY CL Shanghai, PEOPLES R CHINA SP Off Naval Res, Chinese Acad Sci, Acoust Soc China, Acoust Soc Amer, Natl Nat Sci Fdn China ID CATCH-UP GROWTH; LONGITUDINAL BONE-GROWTH; EPIPHYSEAL FUSION; RESTING ZONE; DEXAMETHASONE; CHONDROCYTES; SENESCENCE; RETARDATION; EXPRESSION; RECEPTOR AB Glucocorticoids have a direct, inhibitory effect on the growth plate, as demonstrated by in vivo and organ culture studies. Glucocorticoids slow longitudinal bone growth by inhibiting chondrocyte proliferation, hypertrophy, and cartilage matrix synthesis. The molecular mediators of these effects are poorly understood. Glucocorticoids also delay growth plate senescence. The decreased rate of senescence appears to be a consequence of the growth inhibition and, in particular, may occur because glucocorticoids slow proliferation of stem-like cells in the resting zone and therefore conserve the limited proliferative capacity of these cells. This slowing of senescence appears to explain the phenomenon of catch-up growth following transient glucocorticoid exposure. After the exposure, the growth plate is less senescent, and therefore grows more rapidly than is normal for age. Glucocorticoids cause growth inhibition and subsequent catch-up growth not only in terms of longitudinal bone growth at the growth plate but also in terms of cross-sectional bone growth at the periosteum. Whether the underlying mechanisms are analogous to those at the growth plate is not known. Copyright (C) 2011 S. Karger AG, Basel C1 [Baron, Jeffrey] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Dev Endocrinol Branch, Program Dev Endocrinol & Genet, NIH,CRC, Bethesda, MD 20892 USA. RP Baron, J (reprint author), Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Dev Endocrinol Branch, Program Dev Endocrinol & Genet, NIH,CRC, Room 1-3330,10 Ctr Dr,MSC-1103, Bethesda, MD 20892 USA. EM jeffrey.baron@nih.gov RI Lui, Chun Kin Julian/E-2253-2012 FU Intramural NIH HHS [ZIA HD000640-16] NR 26 TC 11 Z9 11 U1 0 U2 4 PU KARGER PI BASEL PA POSTFACH, CH-4009 BASEL, SWITZERLAND SN 1421-7082 BN 978-3-8055-9643-5 J9 ENDOCR DEV JI Endocr. Dev. PY 2011 VL 20 BP 187 EP 193 PG 7 WC Endocrinology & Metabolism; Pediatrics SC Endocrinology & Metabolism; Pediatrics GA BTJ75 UT WOS:000287122700019 PM 21164272 ER PT J AU Meier, ER Byrnes, C Weissman, M Noel, P Luban, NLC Miller, JL AF Meier, Emily Riehm Byrnes, Colleen Weissman, Maxine Noel, Pierre Luban, Naomi L. C. Miller, Jeffery L. TI Expression Patterns of Fetal Hemoglobin in Sickle Cell Erythrocytes Are Both Patient- and Treatment-Specific During Childhood SO PEDIATRIC BLOOD & CANCER LA English DT Article DE F cells; fetal hemoglobin; sickle cell disease ID DISEASE; CHILDREN; HYDROXYUREA; MANAGEMENT; ANEMIA AB Background Treatment associated fetal hemoglobin (HbF) expression patterns in children with sickle cell disease (SCD) have not been fully described The objective of this study was to corn pare HbF expression profiles (HbF and F cells) in the peripheral blood of pediatric SCD patients receiving hydroxyurea (HU) chronic transfusions (Tx) or no chronic therapy (Ctrl) Procedure Peripheral blood samples were collected from SCD patients between 1 month and 21 years of age and immunostained with anti HbF and anti HbA antibodies Erythrocytes containing HbF (F cells) were enumerated with this dual staining method HbF was measured using chromatography (HPLC) Results Blood from 44 Ctrl patients <= 4 years of age was compared with that from older children (50 Ctrl 17 HU 17 Tx) Among the older children, the percentage of both HbF and F ails in the Tx group was significantly decreased compared to the control (HbF 5 4 +/- 4 2% vs 11 0 +/- 7 2%, P=0 003 F cells 302 +/- 16 3% vs 43 8 +/- 20 4%, P = 0 0071) While the distribution of F cells was significantly increased in the HU group (56 3 +/- 17 1% vs 43 8 20 4%, P=0 016), the increase in HbF was less robust (14 7 +/- 6 4% vs 11 0 +/- 7 2% P = 0 051) Positive correlations of HbF and F cell distributions were noted in all groups (P <0 0001 for all groups) In serial samples from individual patients relatively static patterns of HbF and F cell distribution were noted Conclusion Pediatric SCD patients possess distinct patterns of HbF switching and silencing in peripheral blood erythrocytes Thereafter, erythrocyte HbF expression level and distribution are maintained with both patient and treatment specific patterns that may be useful for predicing the need or response to HbF modulating therapy Pediatr Blood Cancer 2011,56 103-109 (C) 2010 Wiley Liss Inc C1 [Meier, Emily Riehm; Byrnes, Colleen; Miller, Jeffery L.] NIDDK, Mol Med Branch, NIH, Bethesda, MD 20892 USA. [Meier, Emily Riehm; Luban, Naomi L. C.] Childrens Natl Med Ctr, Ctr Canc & Blood Disorders, Washington, DC 20010 USA. [Weissman, Maxine; Noel, Pierre] NIH, Dept Lab Med, Hematol Serv, Bethesda, MD 20892 USA. [Luban, Naomi L. C.] George Washington Univ, Dept Pediat, Med Ctr, Washington, DC 20052 USA. RP Miller, JL (reprint author), NIDDK, Mol Med Branch, NIH, 10 Ctr Dr,Bldg 10,Room 9N311, Bethesda, MD 20892 USA. FU NIH; NIDDK NIH; Children's National Medical Center FX Grant sponsor NIH; This research was supported by the Intramural Research Program of the NIDDK NIH Dr Meier is a scholar in the DC Clinical Research Training Consortium a K30 funded clinical research training program and the recipient of the Tucker Foundation Fellowship at Children's National Medical Center NR 23 TC 7 Z9 7 U1 0 U2 1 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 1545-5009 J9 PEDIATR BLOOD CANCER JI Pediatr. Blood Cancer PD JAN PY 2011 VL 56 IS 1 BP 103 EP 109 DI 10.1002/pbc.22643 PG 7 WC Oncology; Hematology; Pediatrics SC Oncology; Hematology; Pediatrics GA 687PM UT WOS:000284790400020 PM 21108444 ER PT J AU Hull, JJ Teel, EN Kerin, TK Freeman, MM Esona, MD Gentsch, JR Cortese, MM Parashar, UD Glass, RI Bowen, MD AF Hull, Jennifer J. Teel, Elizabeth N. Kerin, Tara K. Freeman, Molly M. Esona, Mathew D. Gentsch, Jon R. Cortese, Margaret M. Parashar, Umesh D. Glass, Roger I. Bowen, Michael D. CA National Rotavirus Strain Surveill TI United States Rotavirus Strain Surveillance From 2005 to 2008 Genotype Prevalence Before and After Vaccine Introduction SO PEDIATRIC INFECTIOUS DISEASE JOURNAL LA English DT Article DE RotaTeq; rotavirus; strain; surveillance; US ID POLYMERASE CHAIN-REACTION; VP4 GENE; POPULATION; GASTROENTERITIS; IDENTIFICATION; DIVERSITY; CHILDREN; PREVENTION; REDUCTION; ROTARIX AB Background: A live, attenuated rotavirus vaccine, RotaTeq (R), was approved in 2006 for immunization of infants in the United States. To monitor the distribution of rotavirus genotypes before and after vaccine introduction, the Centers for Disease Control and Prevention conducted strain surveillance with the National Rotavirus Strain Surveillance System. Methods: Over 3 rotavirus seasons, 2005-2006, 2006-2007, and 2007-2008, National Rotavirus Strain Surveillance System laboratories collected rotavirus-positive stool specimens and submitted them to the Centers for Disease Control and Prevention. Rotavirus strains were G- and P-genotyped by multiplex reverse transcription-polymerase chain reaction or nucleotide sequencing. Results: During 2005-2006 and 2006-2007 seasons, G I was the dominant G-type but in the 2007-2008 season, G3 replaced GI as the most frequently detected strain. Four genotypes, G1P[8], G2P[4], G3P[8], and G9P[8] were detected in every season. Uncommon strains observed during the study period were G2P[8], G1P[6], G2P[6], G4P[6], G1P[4], G3P[9], G12P [6], and G12P[8]. The mean age of rotavirus cases in the 2007-2008 season increased significantly in patients less than 3 years old compared with the 2 previous seasons. Conclusions: The increased overall prevalence of G3P [8] strains in 2007-2008, the first rotavirus season with reasonable rotavirus vaccine coverage, was consistent with Australian reports of G3 dominance following RotaTeq introduction. However, these strain changes in both countries have occurred in the context of large declines in severe rotavirus disease and we cannot rule out that they are simply the result of naturally occurring changes in rotavirus strain prevalence. These findings underscore the need for careful monitoring of strains to assess possible vaccine pressure-induced changes and vaccine effectiveness against various rotavirus genotypes. C1 [Hull, Jennifer J.; Teel, Elizabeth N.; Kerin, Tara K.; Freeman, Molly M.; Esona, Mathew D.; Gentsch, Jon R.; Glass, Roger I.; Bowen, Michael D.] Ctr Dis Control & Prevent, Gastroenteritis & Resp Viruses Lab Branch, Div Viral Dis, Natl Ctr Immunizat & Resp Dis, Atlanta, GA 30333 USA. [Cortese, Margaret M.; Parashar, Umesh D.] Ctr Dis Control & Prevent, Epidemiol Branch, Div Viral Dis, Natl Ctr Immunizat & Resp Dis, Atlanta, GA 30333 USA. [Glass, Roger I.] NIH, Fogarty Int Ctr, Bethesda, MD 20892 USA. RP Bowen, MD (reprint author), Ctr Dis Control & Prevent, Gastroenteritis & Resp Viruses Lab Branch, Div Viral Dis, Natl Ctr Immunizat & Resp Dis, Roybal Campus,Mailstop G04,1600 Clifton Rd NE, Atlanta, GA 30333 USA. EM MKB6@CDC.GOV NR 33 TC 89 Z9 90 U1 0 U2 5 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0891-3668 J9 PEDIATR INFECT DIS J JI Pediatr. Infect. Dis. J. PD JAN PY 2011 VL 30 IS 1 SU S BP S42 EP S47 DI 10.1097/INF.0b013e3181fefd78 PG 6 WC Immunology; Infectious Diseases; Pediatrics SC Immunology; Infectious Diseases; Pediatrics GA 701EA UT WOS:000285795900009 PM 21183839 ER PT J AU Hintz, SR Kendrick, DE Wilson-Costello, DE Das, A Bell, EF Vohr, BR Higgins, RD AF Hintz, Susan R. Kendrick, Douglas E. Wilson-Costello, Deanne E. Das, Abhik Bell, Edward F. Vohr, Betty R. Higgins, Rosemary D. CA NICHD Neonatal Res Network TI Early-Childhood Neurodevelopmental Outcomes Are Not Improving for Infants Born at < 25 Weeks' Gestational Age SO PEDIATRICS LA English DT Article DE extremely preterm; neurodevelopmental; outcome; cerebral palsy; Bayley Scales of Infant Development II ID BIRTH-WEIGHT INFANTS; EXTREMELY PRETERM BIRTH; PERINATAL MANAGEMENT; COGNITIVE FUNCTION; CHILDREN; MOTOR; LESS; CARE AB OBJECTIVE: We compared neurodevelopmental outcomes at 18 to 22 months' corrected age of infants born with extremely low birth weight at an estimated gestational age of <25 weeks during 2 periods: 1999-2001 (epoch 1) and 2002-2004 (epoch 2). PATIENTS AND METHODS: We conducted a multicenter, retrospective analysis of the Eunice Kennedy Shriver National Institute of Child Health and Human Development Neonatal Research Network. Perinatal and neonatal variables and outcomes were compared between epochs. Neurodevelopmental outcomes at 18 to 22 months' corrected age were evaluated with neurologic exams and Bayley Scales of Infant Development II. Logistic regression analyses determined the independent risk of epoch for adverse outcomes. RESULTS: Infant survival was similar between epochs (epoch 1, 35.4%, vs epoch 2, 32.3%; P = .09). A total of 411 of 452 surviving infants in epoch 1 and 405 of 438 surviving infants in epoch 2 were evaluated at 18 to 22 months' corrected age. Cesarean delivery (P = .03), surgery for patent ductus arteriosus (P = .004), and late sepsis (P = .01) were more common in epoch 2, but postnatal steroid use was dramatically reduced (63.5% vs 32.8%; P < .0001). Adverse outcomes at 18 to 22 months' corrected age were common in both epochs. Moderate-to-severe cerebral palsy was diagnosed in 11.1% of surviving infants in epoch 1 and 14.9% in epoch 2 (adjusted odds ratio [OR]: 1.52 [95% confidence interval (CI): 0.86-2.71]; P = .15), the Mental Developmental Index was <70 in 44.9% in epoch 1 and 51% in epoch 2 (OR: 1.30 [95% CI: 0.91-1.87]; P = .15), and neurodevelopmental impairment was diagnosed in 50.1% of surviving infants in epoch 1 and 58.7% in epoch 2 (OR: 1.4 [95% CI: 0.98-2.04]; P = .07). CONCLUSIONS: Early-childhood outcomes for infants born at <25 weeks' estimated gestational age were unchanged between the 2 periods. Pediatrics 2011;127:62-70 C1 [Hintz, Susan R.] Stanford Univ, Sch Med, Div Neonatol, Dept Pediat, Palo Alto, CA 94304 USA. [Kendrick, Douglas E.] RTI Int, Stat & Epidemiol Unit, Res Triangle Pk, NC USA. [Wilson-Costello, Deanne E.] Case Western Reserve Univ, Rainbow Babies & Childrens Hosp, Dept Pediat, Cleveland, OH 44106 USA. [Das, Abhik] RTI Int, Stat & Epidemiol Unit, Rockville, MD USA. [Bell, Edward F.] Univ Iowa, Dept Pediat, Iowa City, IA 52242 USA. [Vohr, Betty R.] Brown Univ, Women & Infants Hosp, Dept Pediat, Providence, RI 02908 USA. [Higgins, Rosemary D.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, NIH, Bethesda, MD USA. RP Hintz, SR (reprint author), Stanford Univ, Sch Med, Div Neonatal & Dev Med, Dept Pediat, 750 Welch Rd,Suite 315, Palo Alto, CA 94304 USA. EM srhintz@stanford.edu FU National Institutes of Health; NICHD FX The National Institutes of Health and the NICHD provided grant support for the NRN's generic database and follow-up studies. Data collected at participating sites of the NICHD NRN were transmitted to RTI International, the data coordinating center (DCC) for the network, which stored, managed, and analyzed the data for this study. On behalf of the NRN, Dr Abhik Das (DCC Principal Investigator) and Mr Douglas Kendrick (DCC Statistician) had full access to all the data in the study and take responsibility for the integrity of the data and accuracy of the data analysis. NR 29 TC 69 Z9 70 U1 2 U2 2 PU AMER ACAD PEDIATRICS PI ELK GROVE VILLAGE PA 141 NORTH-WEST POINT BLVD,, ELK GROVE VILLAGE, IL 60007-1098 USA SN 0031-4005 J9 PEDIATRICS JI Pediatrics PD JAN PY 2011 VL 127 IS 1 BP 62 EP 70 DI 10.1542/peds.2010-1150 PG 9 WC Pediatrics SC Pediatrics GA 700YT UT WOS:000285782200046 PM 21187312 ER PT J AU Ambalavanan, N Walsh, M Bobashev, G Das, A Levine, B Carlo, WA Higgins, RD AF Ambalavanan, Namasivayam Walsh, Michele Bobashev, Georgiy Das, Abhik Levine, Burton Carlo, Waldemar A. Higgins, Rosemary D. TI Intercenter Differences in Bronchopulmonary Dysplasia or Death Among Very Low Birth Weight Infants SO PEDIATRICS LA English DT Article DE logistic models; infant; premature; predictive value of tests; clustering ID NEONATAL INTENSIVE-CARE; QUALITY IMPROVEMENT; PRETERM INFANTS; OUTCOMES; RATES AB OBJECTIVES: To determine (1) the magnitude of clustering of bronchopulmonary dysplasia (36 weeks) or death (the outcome) across centers of the Eunice Kennedy Shriver National Institute of Child and Human Development National Research Network, (2) the infant-level variables associated with the outcome and estimate their clustering, and (3) the center-specific practices associated with the differences and build predictive models. METHODS: Data on neonates with a birth weight of <1250 g from the cluster-randomized benchmarking trial were used to determine the magnitude of clustering of the outcome according to alternating logistic regression by using pairwise odds ratio and predictive modeling. Clinical variables associated with the outcome were identified by using multivariate analysis. The magnitude of clustering was then evaluated after correction for infant-level variables. Predictive models were developed by using center-specific and infant-level variables for data from 2001 2004 and projected to 2006. RESULTS: In 2001-2004, clustering of bronchopulmonary dysplasia/death was significant (pairwise odds ratio: 1.3; P < .001) and increased in 2006 (pairwise odds ratio: 1.6; overall incidence: 52%; range across centers: 32%-74%); center rates were relatively stable over time. Variables that varied according to center and were associated with increased risk of outcome included lower body temperature at NICU admission, use of prophylactic indomethacin, specific drug therapy on day 1, and lack of endotracheal intubation. Center differences remained significant even after correction for clustered variables. CONCLUSION: Bronchopulmonary dysplasia/death rates demonstrated moderate clustering according to center. Clinical variables associated with the outcome were also clustered. Center differences after correction of clustered variables indicate presence of as-yet unmeasured center variables. Pediatrics 2011;127:e106-e116 C1 [Ambalavanan, Namasivayam; Carlo, Waldemar A.] Univ Alabama, Dept Pediat, Birmingham, AL 35249 USA. [Walsh, Michele] Case Western Reserve Univ, Dept Pediat, Cleveland, OH 44106 USA. [Bobashev, Georgiy; Das, Abhik; Levine, Burton] RTI Int, Res Triangle Pk, NC USA. [Higgins, Rosemary D.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Bethesda, MD USA. [Higgins, Rosemary D.] Dev Neonatal Res Network, Bethesda, MD USA. RP Ambalavanan, N (reprint author), Univ Alabama, Dept Pediat, 176F Suite 9380,619 S 20th St, Birmingham, AL 35249 USA. EM ambal@uab.edu OI Ambalavanan, Namasivayam/0000-0003-0731-9092 FU National Institutes of Health; Eunice Kennedy Shriver National Institute of Child Health and Human Health and Development; Department of Health and Human Services [U10 HD21385, U10 HD40689, U10 HD27871, U10 HD21373, U01 HD36790, U10 HD40498, U10 HD40461, U10 HD34216, U10 HD21397, U10 HD27904, U10 HD40492, U10 HD27856, U10 HD40521, U10 HD27853, U10 HD27880, U10 HD27851]; National Institutes of Health [GCRC M01 RR 08084, M01 RR 00125, M01 RR 00750, M01 RR 00070, M01 RR 0039-43, M01 RR 00039, 5 M01 RR00044] FX The National Institutes of Health and the Eunice Kennedy Shriver National Institute of Child Health and Human Health and Development provided grant support for the NRN's benchmarking study (recruitment March 1, 2001, to April 30, 2004) and generic database study (recruitment January to December 2006). This work was supported by grants from the Eunice Kennedy Shriver National Institute of Child Health and Human Health and Development and the Department of Health and Human Services (U10 HD21385, U10 HD40689, U10 HD27871, U10 HD21373, U01 HD36790, U10 HD40498, U10 HD40461, U10 HD34216, U10 HD21397, U10 HD27904, U10 HD40492, U10 HD27856, U10 HD40521, U10 HD27853, U10 HD27880, U10 HD27851) and from the National Institutes of Health (GCRC M01 RR 08084, M01 RR 00125, M01 RR 00750, M01 RR 00070, M01 RR 0039-43, M01 RR 00039, and 5 M01 RR00044). Data collected at participating sites of the Eunice Kennedy Shriver National Institute of Child Health and Human Health and Development NRN were transmitted to RTI International, the data coordinating center for the network, which stored, managed and analyzed the data for this study. On behalf of the NRN, Drs Abhik Das (data coordinating center principal investigator) and Georgiy Bobashev (data coordinating center statistician) had full access to all the data in the study and take responsibility for the integrity of the data and accuracy of the data analysis.; The following investigators, in addition to those listed as authors, participated in this study (National Institutes of Health grant numbers are listed also): NRN chair: Alan Jobe, MD PhD, University of Cincinnati; Cincinnati Children's Hospital Medical Center, University of Cincinnati Hospital and Good Samaritan Hospital (GCRC M01 RR8084, U10 HD27853): Edward F. Donovan, MD, Kurt Schibler, MD, Kathleen Bridges, MD, Barbara Alexander, RN, Cathy Grisby, BSN, CCRC, Jody Hessling, RN, Holly L. Mincey, RN, BSN, and Marcia Worley Mersmann, RN, CCRC; Duke University School of Medicine University Hospital, Alamance Regional Medical Center, and Durham Regional Hospital (GCRC M01 RR30, U10 HD40492): Ronald N. Goldberg, MD, C. Michael Cotten, MD, MHS, and Kathy Auten, MSHS; Emory University Children's Health Care of Atlanta, Grady Memorial Hospital, and Emory Crawford Long Hospital (GCRC M01 RR39, U10 HD27851): Barbara J. Stoll, MD, Susie Buchter, MD, Ellen C. Hale, R, RN, BS, CCRC; Eunice Kennedy Shriver National Institute of Child Health and Human Development: Linda L. Wright, MD, Rosemary D. Higgins, MD, Elizabeth M. McClure, Med; Indiana University Indiana University Hospital, Methodist Hospital, Riley Hospital for Children, and Wishard Health Services (GCRC M01 RR750, U10 HD27856): James A. Lemons, MD, Brenda B. Poindexter, MD, MS, William A. Engle, MD, Diana D. Appel, RN, BSN, Dianne Herron, RN, Lucy Miller, RN, BSN, CCRC, Richard Hooper, RRT; Rainbow Babies & Children's Hospital (GCRC M01 RR80, U10 HD21364): Avroy A. Fanaroff, MD, Nancy S. Newman, RN; RTI International (U01 HD36790): W. Kenneth Poole, PhD, Betty Hastings, Elizabeth McClure, Med, Qing Yao, PhD, Jeanette O'Donnell Auman, BS, Carolyn Petrie Huitema, MS, Scott E. Schaefer, MS, Kristin M. Zaterka-Baxter, RN; Stanford University Lucile Packard Children's Hospital (GCRC M01 RR70, U10 HD27880): David K. Stevenson, MD, Krisa P. Van Meurs, MD, William D. Rhine, MD, M. Bethany Ball, BS, CCRC, Carol Kibler, RN, Jeffrey R. Parker, RRT; Tufts Medical Center Floating Hospital for Children (GCRC M01 RR54, U10 HD53119): Ivan D. Frantz, III, MS, Brenda L. MacKinnon, RNC, Ellen Nylen, RN, University of Alabama at Birmingham Health System and Children's Hospital of Alabama (GCRC M01 RR32, U10 HD34216): Monica V. Collins, RN, BSN, MaEd, Shirley S. Cosby, RN, BSN; University of California, San Diego Medical Center and Sharp Mary Birch Hospital for Women (U10 HD40461): Neil N. Finer, MD, Maynard R. Rasmussen, MD, Paul R. Wozniak, MD, Greg Heldt, MD, Kathy Arnell, RNC, Clarence Demetrio, RN, Chris Henderson, RCP, CRTT, Wade Rich, BSHS, RRT, Mindy Grabarczyk, BSN, Christina Joseph, RRT, Renee Bridge, RN, Jim Goodmar, RRT; University of Iowa Children's Hospital (GCRC M01 RR59, U10 HD53109): Edward F. Bell, MD, Karen J. Johnson, RN, BSN; University of Miami Holtz Children's Hospital (GCRC M01 RR16587, U10 HD21397): Shahnaz Duara, MD, Ruth Everett-Thomas, RN, MSN; University of New Mexico Health Sciences Center (GCRC M01 RR997, U10 HD53089): Kristi L. Watterberg, MD, Conra Backstrom Lacy, RN; University of Rochester Golisano Children's Hospital at Strong (GCRC M01 RR44, U10 HD40521): Dale L. Phelps, MD, Robert A. Sinkin, MD, Linda Reubens, RN; University of Texas Southwestern Medical Center at Dallas Parkland Health & Hospital System and Children's Medical Center Dallas (GCRC M01 RR633, U10 HD40689): Abbot R. Laptook, MD, Walid A. Salhab, MD, Charles R. Rosenfeld, MD, Pablo J. Sanchez, MD, James Allen, RRT, Alicia Guzman, Gay Hensley, RN, Susie Madison, RN, Melissa Martin, RN, Nancy A.; Miller, RN; niversity of Texas Health Science Center at Houston, Medical School, Children's Memorial Hermann Hospital, and Lydon Baines Johnson General Hospital (U10 HD21373): Jon E. Tyson, MD, MPH, Kathleen A. Kennedy, MD, MPH, Esther G. Akpa, RN, BSN, Patty A. Cluff, RN, Claudia I. Franco, RNC, MSN, Anna E. Lis, RN, BSN, Georgia E. McDavid, RN, Nora I. Alaniz, BS, Patti Pierce Tate, RCP, University of Utah University Hospital, LDS Hospital, and Primary Children's Medical Center (GCRC M01 RR64, U10 HD53124): Roger G. Faix, MD, Bradley A. Yoder, MD, Karen A. Osborne, RN, BSN, Jennifer J. Jensen, RN, BSN, Wake Forest University Baptist Medical Center, Brenner Children's Hospital, and Forsyth Medical Center (GCRC M01 RR7122, U10 HD40498): T. Michael O'Shea, MD, MPH, Nancy J. Peters, RN, CCRP; Wayne State University Hutzel Women's Hospital and Children's Hospital of Michigan (U10 HD21385): Seetha Shankaran, MD, Rebecca Bara, RN, BSN, Geraldine Muran, RN, BSN, S. Nadya Kazzi, MD, MPH, Kimberly Hayes-Hart, RN, MSN, NNP-BC, Maria Batts, RRT; Women & Infants Hospital of Rhode Island (U10 HD27904): William Oh, MD, Abbot R. Laptook, MD, Angelita Hensman, BSN, RNC; Yale University Yale-New Haven Children's Hospital (GCRC M01 RR125, GCRC M01 RR6022, U10 HD27871): Richard A. Ehren-kranz, MD, Patricia Gettner, RN, Monica Konstantino, RN, BSN, JoAnn Poulsen, RN. NR 18 TC 34 Z9 34 U1 2 U2 4 PU AMER ACAD PEDIATRICS PI ELK GROVE VILLAGE PA 141 NORTH-WEST POINT BLVD,, ELK GROVE VILLAGE, IL 60007-1098 USA SN 0031-4005 J9 PEDIATRICS JI Pediatrics PD JAN PY 2011 VL 127 IS 1 BP E106 EP E116 DI 10.1542/peds.2010-0648 PG 11 WC Pediatrics SC Pediatrics GA 700YT UT WOS:000285782200014 PM 21149431 ER PT B AU Franquelim, HG Matos, PM Veiga, AS AF Franquelim, Henri G. Matos, Pedro M. Salome Veiga, A. BE Castanho, M Santos, NC TI HIV vs. HIV: Turning HIV-Derived Peptides into Drugs SO PEPTIDE DRUG DISCOVERY AND DEVELOPMENT: TRANSLATIONAL RESEARCH IN ACADEMIA AND INDUSTRY LA English DT Article; Book Chapter ID IMMUNODEFICIENCY-VIRUS TYPE-1; FUSION INHIBITOR PEPTIDES; HEPTAD REPEAT REGION; IN-VITRO SYNERGY; CELL-CELL FUSION; MEMBRANE-FUSION; ENTRY INHIBITORS; ENVELOPE GLYCOPROTEIN; ANTIRETROVIRAL ACTIVITY; POTENT INHIBITORS C1 [Franquelim, Henri G.; Matos, Pedro M.; Salome Veiga, A.] Univ Lisbon, Inst Med Mol, Fac Med, P-1649028 Lisbon, Portugal. [Salome Veiga, A.] NCI, Biol Chem Lab, Frederick, MD 21702 USA. RP Franquelim, HG (reprint author), Univ Lisbon, Inst Med Mol, Fac Med, Av Prof Egas Moniz, P-1649028 Lisbon, Portugal. OI Veiga, Ana Salome/0000-0002-9892-2243 NR 91 TC 1 Z9 1 U1 1 U2 1 PU WILEY-V C H VERLAG GMBH PI WEINHEIM PA PAPPELALLEE 3, W-69469 WEINHEIM, GERMANY BN 978-3-527-63675-4; 978-3-527-32891-8 PY 2011 BP 209 EP 229 D2 10.1002/9783527636730 PG 21 WC Biochemistry & Molecular Biology; Chemistry, Medicinal; Pharmacology & Pharmacy SC Biochemistry & Molecular Biology; Pharmacology & Pharmacy GA BA9PZ UT WOS:000339712000011 ER PT J AU Nasr, S Ungerleider, L Tootell, R AF Nasr, S. Ungerleider, L. Tootell, R. TI Parallel streams recognition of face versus non-face objects in human temporal lobe SO PERCEPTION LA English DT Meeting Abstract C1 [Ungerleider, L.] NIH, Bethesda, MD 20892 USA. EM shahin@nmr.mgh.harvard.edu NR 0 TC 0 Z9 0 U1 0 U2 1 PU PION LTD PI LONDON PA 207 BRONDESBURY PARK, LONDON NW2 5JN, ENGLAND SN 0301-0066 J9 PERCEPTION JI Perception PY 2011 VL 40 SU S BP 25 EP 25 PG 1 WC Ophthalmology; Psychology; Psychology, Experimental SC Ophthalmology; Psychology GA V27PI UT WOS:000208624700079 ER PT J AU Arizpe, J Kravitz, D Yovel, G Baker, C AF Arizpe, J. Kravitz, D. Yovel, G. Baker, C. TI Differences in looking at own-race and other-race faces SO PERCEPTION LA English DT Meeting Abstract C1 [Arizpe, J.; Kravitz, D.; Baker, C.] NIMH, Bethesda, MD USA. [Yovel, G.] Tel Aviv Univ, Tel Aviv, Israel. EM bakerchris@mail.nih.gov NR 0 TC 0 Z9 0 U1 0 U2 0 PU PION LTD PI LONDON PA 207 BRONDESBURY PARK, LONDON NW2 5JN, ENGLAND SN 0301-0066 J9 PERCEPTION JI Perception PY 2011 VL 40 SU S BP 155 EP 155 PG 1 WC Ophthalmology; Psychology; Psychology, Experimental SC Ophthalmology; Psychology GA V27PI UT WOS:000208624700495 ER PT J AU Finkelstein, FO Juergensen, P Wang, SX Santacroce, S Levine, M Kotanko, P Levin, NW Handelman, GJ AF Finkelstein, Fredric O. Juergensen, Peter Wang, Suxin Santacroce, Sally Levine, Mark Kotanko, Peter Levin, Nathan W. Handelman, Garry J. TI HEMOGLOBIN AND PLASMA VITAMIN C LEVELS IN PATIENTS ON PERITONEAL DIALYSIS SO PERITONEAL DIALYSIS INTERNATIONAL LA English DT Article DE Vitamin C; hemoglobin; anemia ID CHRONIC-HEMODIALYSIS PATIENTS; INTRAVENOUS ASCORBIC-ACID; DEHYDROASCORBIC ACID; IRON-ABSORPTION; DEFICIENCY; ERYTHROPOIETIN; INFLAMMATION; FERRITIN; WOMEN; SUPPLEMENTATION AB Objective: To determine the contribution of vitamin C (Vit C) status in relation to hemoglobin (Hb) levels in patients on long-term peritoneal dialysis (PD). Methods: 56 stable PD patients were evaluated in a cross-sectional survey. Plasma samples were collected for Vit C (analyzed by HPLC with electrochemical detection) and high-sensitivity C-reactive protein (hs-CRP) determinations. Clinical records were reviewed for Hb, transferrin saturation (TSAT), ferritin, erythropoietin (EPO) dose, and other clinical parameters. Dietary Vit C intake was evaluated by patient survey and from patient records. Total Vit C removed during PD treatment was measured in 24-hour dialysate collections. Results: Patients showed a highly skewed distribution of plasma Vit C levels, with 40% of patients below normal plasma Vit C levels (<30 mu mol/L) and 9% at higher than normal levels (>80 mu mol/L). Higher plasma Vit C levels were associated with higher Hb levels (Pearson r = 0.33, p < 0.004). No direct connection between Vit C levels and reported dietary intake could be established. In stepwise multiple regression, plasma Vit C remained significantly associated with Hb (p = 0.017) but there was no significant association with other variables (dialysis vintage, age, ferritin, TSAT, hs-CRP, residual renal function, and EPO dose). In 9 patients that were evaluated for Vit C in dialysate, plasma Vit C was positively associated (Spearman r = 0.85, p = 0.01) with the amount of Vit C removed during dialysis treatment. Conclusions: These data indicate that plasma Vit C is positively associated with higher Hb level. Vit C status could play a major role in helping PD patients to utilize iron for erythropoiesis and achieve a better Hb response during anemia management. C1 [Handelman, Garry J.] Univ Massachusetts, Clin Lab Sci & Nutr, Lowell, MA 01854 USA. [Finkelstein, Fredric O.; Juergensen, Peter; Santacroce, Sally] New Haven CAPD, New Haven, CT USA. [Finkelstein, Fredric O.] Hosp St Raphael, New Haven, CT 06511 USA. [Finkelstein, Fredric O.] Yale Univ, New Haven, CT USA. [Levine, Mark] NIDDK, NIH, Bethesda, MD USA. [Kotanko, Peter; Levin, Nathan W.; Handelman, Garry J.] Renal Res Inst, New York, NY USA. RP Handelman, GJ (reprint author), Univ Massachusetts, Clin Lab Sci & Nutr, 3 Solomont Way, Lowell, MA 01854 USA. EM garry_handelman@uml.edu FU Renal Research Institute FX Financial support was provided by a gift from the Renal Research Institute. NR 38 TC 8 Z9 9 U1 1 U2 3 PU MULTIMED INC PI TORONTO PA 66 MARTIN ST, TORONTO, ON L9T 2R2, CANADA SN 0896-8608 J9 PERITON DIALYSIS INT JI Perit. Dial. Int. PD JAN-FEB PY 2011 VL 31 IS 1 BP 74 EP 79 DI 10.3747/pdi.2009.00154 PG 6 WC Urology & Nephrology SC Urology & Nephrology GA 713HN UT WOS:000286726800014 PM 20558814 ER PT J AU DeBono, A Shmueli, D Muraven, M AF DeBono, Amber Shmueli, Dikla Muraven, Mark TI Rude and Inappropriate: The Role of Self-Control in Following Social Norms SO PERSONALITY AND SOCIAL PSYCHOLOGY BULLETIN LA English DT Article DE norms; self-regulation; self-control; self; morality; individual differences ID HIRSCHIS GENERAL-THEORY; LIMITED RESOURCES; CONTROL STRENGTH; EMPIRICAL-TEST; CRIME; DEPLETION; GOTTFREDSON; EMOTIONALITY; DETERRENCE; MANAGEMENT AB Following social norms to avoid deviant or socially inappropriate behavior may require self-control. This was tested in two experiments that experimentally manipulated individuals' level of self-control strength. In the first experiment, individuals whose self-control capacity was depleted were more likely to misrepresent how many problems they solved and work after being told to stop while working on a timed test. These same results were found in individuals low in trait self-control. This was especially true when the certainty of getting caught was low. In the second experiment, depleted individuals were ruder to the experimenter than nondepleted participants. The results have implications for understanding how self-control contributes to normative behavior. C1 [DeBono, Amber; Muraven, Mark] SUNY Albany, Albany, NY 12065 USA. [Shmueli, Dikla] NCI, Bathesda, MD USA. RP DeBono, A (reprint author), SUNY Albany, 1400 Washington Ave, Albany, NY 12065 USA. EM amberdebono@yahoo.com RI Muraven, Mark/A-5725-2009 OI Muraven, Mark/0000-0003-3057-4323 FU NIAAA NIH HHS [AA12770]; NIDA NIH HHS [DA015131] NR 41 TC 14 Z9 16 U1 3 U2 24 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 0146-1672 J9 PERS SOC PSYCHOL B JI Pers. Soc. Psychol. Bull. PD JAN PY 2011 VL 37 IS 1 BP 136 EP 146 DI 10.1177/0146167210391478 PG 11 WC Psychology, Social SC Psychology GA 697UP UT WOS:000285544600011 PM 21177879 ER PT S AU Barchi, JJ AF Barchi, Joseph J., Jr. BE Huang, X Barchi, JJ TI Glyco-Nanoparticles as Platforms for Antitumor Therapeutic Strategies SO PETITE AND SWEET: GLYCO-NANOTECHNOLOGY AS A BRIDGE TO NEW MEDICINES SE ACS Symposium Series LA English DT Proceedings Paper CT Symposium on Petite and Sweet: Glyco-Nanotechnology as a Bridge to New Medicines CY AUG 22-26, 2010 CL Boston, MA SP GP BioSciences, Omicron, ACS, Div Carbohydrate Chem ID THOMSEN-FRIEDENREICH DISACCHARIDE; CARBOHYDRATE-CARBOHYDRATE INTERACTIONS; ENTRAPPED GOLD NANOPARTICLES; VACCINE DELIVERY-SYSTEMS; CANCER-THERAPY; IMMUNE-RESPONSES; BIOMEDICAL APPLICATIONS; DENDRITIC CELLS; IN-VITRO; MAGNETIC GLYCONANOPARTICLES AB There has been an explosion of progress in the development of novel nanotechnology-based platforms for a variety of applications. One reason for this development is that the properties of nanomaterials (optical, scattering, physical) can be dramatically different than those of macro-based technologies. Many of these unique properties can be exploited to develop novel imaging agents and delivery systems. A host of biologically relevant molecules can be conjugated to nanoparticles to functionalize these platforms. Cellular glycans are one family of biomolecules that have been coated on different nanoparticle platforms and some of these tools are being successfully employed for specific biomedical applications. To date however, the application of these so-called glyconanoparticles for antitumor therapeutics has been sparse. Fortunately, some initial results with glyconanoparticles have been very encouraging for possible translation to clinically relevant anti-tumor therapies. This chapter will examine the most recent work reported on the synthesis, development and application of the most promising platforms. C1 NCI, Biol Chem Lab, Mol Discovery Program, Ctr Canc Res, Frederick, MD 21702 USA. RP Barchi, JJ (reprint author), NCI, Biol Chem Lab, Mol Discovery Program, Ctr Canc Res, Frederick, MD 21702 USA. EM barchi@helix.nih.gov RI Barchi Jr., Joseph/N-3784-2014 NR 128 TC 4 Z9 4 U1 3 U2 14 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 SIXTEENTH ST NW, WASHINGTON, DC 20036 USA SN 0097-6156 BN 978-0-8412-2688-3 J9 ACS SYM SER JI ACS Symp. Ser. PY 2011 VL 1091 BP 161 EP 179 PG 19 WC Biotechnology & Applied Microbiology; Nanoscience & Nanotechnology SC Biotechnology & Applied Microbiology; Science & Technology - Other Topics GA BDF52 UT WOS:000313021800010 ER PT J AU Frohlich, H Boini, KM Seebohm, G Strutz-Seebohm, N Ureche, ON Foller, M Eichenmuller, M Shumilina, E Pathare, G Singh, AK Seidler, U Pfeifer, KE Lang, F AF Froehlich, Henning Boini, Krishna M. Seebohm, Guiscard Strutz-Seebohm, Nathalie Ureche, Oana N. Foeller, Michael Eichenmueller, Melanie Shumilina, Ekaterina Pathare, Ganesh Singh, Anurag Kumar Seidler, Ursula Pfeifer, Karl E. Lang, Florian TI Hypothyroidism of gene-targeted mice lacking Kcnq1 SO PFLUGERS ARCHIV-EUROPEAN JOURNAL OF PHYSIOLOGY LA English DT Article DE K(+) channels; Body temperature; Thyroid hormones; T3/T4; TSH; KCNE; Chromanol ID POTASSIUM CHANNEL; PARIETAL-CELLS; ION CHANNELS; K+ CHANNELS; MEMBRANE; KVLQT1; VOLUME; EXPRESSION; PROTEIN; RAT AB Thyroid hormones T3/T4 participate in the fine tuning of development and performance. The formation of thyroid hormones requires the accumulation of I(-) by the electrogenic Na(+)/I(-) symporter, which depends on the electrochemical gradient across the cell membrane and thus on K(+) channel activity. The present paper explored whether Kcnq1, a widely expressed voltage-gated K(+) channel, participates in the regulation of thyroid function. To this end, Kcnq1 expression was determined by RT-PCR, confocal microscopy, and thyroid function analyzed in Kcnq1 deficient mice (Kcnq1(-/-)) and their wild-type littermates (Kcnq1(+/+)). Moreover, Kcnq1 abundance and current were determined in the thyroid FRTL-5 cell line. Furthermore, mRNA encoding KCNQ1 and the subunits KCNE1-5 were discovered in human thyroid tissue. According to patch-clamp TSH (10 mUnits/ml) induced a voltage-gated K(+) current in FRTL-5 cells, which was inhibited by the Kcnq inhibitor chromanol (10 mu M). Despite a tendency of TSH plasma concentrations to be higher in Kcnq1(-/-) than in Kcnq1(+/+) mice, the T3 and T4 plasma concentrations were significantly smaller in Kcnq1(-/-) than in Kcnq1(+/+) mice. Moreover, body temperature was significantly lower in Kcnq1(-/-) than in Kcnq1(+/+) mice. In conclusion, Kcnq1 is required for proper function of thyroid glands. C1 [Froehlich, Henning; Boini, Krishna M.; Ureche, Oana N.; Foeller, Michael; Eichenmueller, Melanie; Shumilina, Ekaterina; Pathare, Ganesh; Lang, Florian] Univ Tubingen, Dept Physiol, D-72076 Tubingen, Germany. [Seebohm, Guiscard; Strutz-Seebohm, Nathalie] Ruhr Univ Bochum, Dept Biochem 1, D-44780 Bochum, Germany. [Ureche, Oana N.] Univ Tubingen, Dept Mol Pathol, D-72076 Tubingen, Germany. [Singh, Anurag Kumar; Seidler, Ursula] Hannover Med Sch, Dept Gastroenterol Hepatol & Endocrinol, D-30625 Hannover, Germany. [Pfeifer, Karl E.] NICHD, Lab Mammalian Genes & Dev, NIH, Bethesda, MD USA. RP Lang, F (reprint author), Univ Tubingen, Dept Physiol, Gmelinstr 5, D-72076 Tubingen, Germany. EM florian.lang@uni-tuebingen.de RI Boini, Krishna/H-3548-2011; OI Pfeifer, Karl/0000-0002-0254-682X FU Deutsche Forschungsgemeinschaft [GK 1302, Se460/9-6] FX The authors acknowledge the technical assistance of E. Faber, R. Engelhardt, B. Rausch, and Dr. B. Riederer for breeding and genotyping kcnq1-/- and kcnq1+/+ mice. The manuscript was meticulously prepared by T. Loch and L. Subasic. This study was supported by the Deutsche Forschungsgemeinschaft (GK 1302) and Se460/9-6 (to U.S.). NR 43 TC 14 Z9 14 U1 0 U2 1 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0031-6768 J9 PFLUG ARCH EUR J PHY JI Pflugers Arch. PD JAN PY 2011 VL 461 IS 1 BP 45 EP 52 DI 10.1007/s00424-010-0890-5 PG 8 WC Physiology SC Physiology GA 710KX UT WOS:000286511600004 PM 20978783 ER PT J AU Yao, MY Roberts, DD Isenberg, JS AF Yao, Mingyi Roberts, David D. Isenberg, Jeff S. TI Thrombospondin-1 inhibition of vascular smooth muscle cell responses occurs via modulation of both cAMP and cGMP SO PHARMACOLOGICAL RESEARCH LA English DT Article DE cAMP; cGMP; Thrombospondin-1; Vascular smooth muscle cells ID ISCHEMIC TISSUE SURVIVAL; NITRIC-OXIDE; CARDIOVASCULAR-SYSTEM; SIGNAL-TRANSDUCTION; CYCLIC-GMP; MYOSIN PHOSPHORYLATION; ADENYLATE-CYCLASE; CHEMOTAXIS; RELAXATION; PHOSPHODIESTERASE-3 AB Nitric oxide (NO) drives pro-survival responses in vascular cells and limits platelet adhesion, enhancing blood flow and minimizing thrombosis. The matricellular protein thrombospondin-1 (TSP1), through interaction with its receptor CD47, inhibits soluble guanylyl cyclase (sGC) activation by NO in vascular cells. In vascular smooth muscle cells (VSMCs) both intracellular cGMP and cAMP regulate adhesion, contractility, proliferation, and migration. cGMP can regulate cAMP through feedback control of hydrolysis. Inhibition of the cAMP phosphodiesterase-4 selectively interfered with the ability of exogenous TSP1 to block NO-driven VSMC adhesion but not cGMP accumulation, suggesting that cAMP also contributes to VSMC regulation by TSP1. Inhibition of phosphodiesterase-4 was sufficient to elevate cAMP levels, and inhibiting guanylyl cyclase or phosphodiesterase-3, or adding exogenous TSP1 reversed this increase in cAMP. Thus, TSP1 regulates VSMC cAMP levels in part via cGMP-dependent inhibition of phosphodiesterase-3. Additionally basal cAMP levels were consistently elevated in both VSMCs and skeletal muscle from TSP1 null mice, and treating null cells with exogenous TSP1 suppressed cAMP levels to those of wild type cells. TSP1 inhibited both forskolin and isoproterenol stimulated increases in cAMP in VSMCs. TSP1 also abrogated forskolin and isoproterenol stimulated vasodilation. Consistent with its ability to directly limit adenylyl cyclase-activated vasodilation, TSP1 also limited cAMP-induced dephosphorylation of myosin light chain-2. These findings demonstrate that TSP1 limits both cGMP and cAMP signaling pathways and functional responses in VSMCs and arteries, by both phosphodiesterase-dependent cross talk between these second messengers and by inhibition of adenylyl cyclase activation. (C) 2010 Elsevier Ltd. All rights reserved. C1 [Yao, Mingyi; Isenberg, Jeff S.] Univ Pittsburgh, Vasc Med Inst, Pittsburgh, PA 15261 USA. [Isenberg, Jeff S.] Univ Pittsburgh, Div Pulm Allergy & Crit Care Med, Sch Med, Pittsburgh, PA 15261 USA. [Roberts, David D.] NCI, Pathol Lab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. RP Isenberg, JS (reprint author), Univ Pittsburgh, Vasc Med Inst, 10048 Biomed Sci Tower 3,3501 5th Ave, Pittsburgh, PA 15261 USA. EM jsi5@pitt.edu RI Roberts, David/A-9699-2008 OI Roberts, David/0000-0002-2481-2981 FU NIH [K22 CA128616]; NIH, National Cancer Institute, Center for Cancer Research FX This research was supported by the following funding: NIH grant K22 CA128616 (JSI) and the Intramural Research Program of the NIH, National Cancer Institute, Center for Cancer Research (DDR). NR 56 TC 20 Z9 20 U1 0 U2 4 PU ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD PI LONDON PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND SN 1043-6618 J9 PHARMACOL RES JI Pharmacol. Res. PD JAN PY 2011 VL 63 IS 1 BP 13 EP 22 DI 10.1016/j.phrs.2010.10.014 PG 10 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 722HH UT WOS:000287422800003 PM 20971192 ER PT J AU Laskin, J Yang, ZB Woods, AS AF Laskin, Julia Yang, Zhibo Woods, Amina S. TI Competition between covalent and noncovalent bond cleavages in dissociation of phosphopeptide-amine complexes SO PHYSICAL CHEMISTRY CHEMICAL PHYSICS LA English DT Article ID SURFACE-INDUCED DISSOCIATION; NEGATIVE-ION FRAGMENTATIONS; RESONANCE MASS-SPECTROMETRY; PROTEIN-LIGAND COMPLEXES; CLUSTER-PHASE REACTIONS; GAS-PHASE; PEPTIDE IONS; VANCOMYCIN ANTIBIOTICS; DEPROTONATED PEPTIDES; AMAZING STABILITY AB Interactions between quaternary amino or guanidino groups with anions are ubiquitous in nature and have been extensively studied phenomenologically. However, little is known about the binding energies in non-covalent complexes containing these functional groups. Here, we present a first study focused on quantifying such interactions using complexes of phosphorylated A(3)pXA(3)-NH2 (X = S, T, Y) peptides with decamethonium (DCM) or diaguanidinodecane (DGD) ligands as model systems. Time-and collision energy-resolved surface-induced dissociation (SID) of the singly charged complexes was examined using a specially configured Fourier transform ion cyclotron resonance mass spectrometer (FTICR-MS). Dissociation thresholds and activation energies were obtained from RRKM modeling of the experimental data that has been described and carefully characterized in our previous studies. For systems examined in this study, covalent bond cleavages resulting in phosphate abstraction by the cationic ligand are characterized by low dissociation thresholds and relatively tight transition states. In contrast, high dissociation barriers and large positive activation entropies were obtained for cleavages of non-covalent bonds. Dissociation parameters obtained from the modeling of the experimental data are in excellent agreement with the results of density functional theory (DFT) calculations. Comparison between the experimental data and theoretical calculations indicate that phosphate abstraction by the ligand is rather localized and mainly affected by the identity of the phosphorylated side chain. The hydrogen bonding in the peptide and ligand properties play a minor role in determining the energetics and dynamics of the phosphate abstraction channel. C1 [Laskin, Julia; Yang, Zhibo] Pacific NW Natl Lab, Chem & Mat Sci Div, Richland, WA 99352 USA. [Woods, Amina S.] NIDA IRP, Struct Biol Unit, Cellular Neurobiol Branch, NIH, Baltimore, MD 21224 USA. RP Laskin, J (reprint author), Pacific NW Natl Lab, Chem & Mat Sci Div, POB 999,K8-88, Richland, WA 99352 USA. EM Julia.Laskin@pnl.gov RI Laskin, Julia/H-9974-2012 OI Laskin, Julia/0000-0002-4533-9644 FU W. R. Wiley Environmental Molecular Sciences Laboratory (EMSL); Division of Chemical Sciences, Geosciences, and Biosciences, Office of Basic Energy Sciences of the U. S. Department of Energy (DOE); National Institute on Drug Abuse, NIH; DOE's Office of Biological and Environmental Research; U. S. Department of Energy [DE-AC05-76RL01830] FX This study was partially supported by the W. R. Wiley Environmental Molecular Sciences Laboratory (EMSL) user program, by a grant from the Division of Chemical Sciences, Geosciences, and Biosciences, Office of Basic Energy Sciences of the U. S. Department of Energy (DOE), and by the Intramural Research Program of the National Institute on Drug Abuse, NIH. The research described in this manuscript was performed using EMSL, a national scientific user facility sponsored by the DOE's Office of Biological and Environmental Research and located at Pacific Northwest National Laboratory (PNNL). PNNL is operated by Battelle for the U. S. Department of Energy under contract DE-AC05-76RL01830. NR 57 TC 7 Z9 7 U1 0 U2 16 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 2011 VL 13 IS 15 BP 6936 EP 6946 DI 10.1039/c1cp00029b PG 11 WC Chemistry, Physical; Physics, Atomic, Molecular & Chemical SC Chemistry; Physics GA 742NL UT WOS:000288951000020 PM 21387029 ER PT J AU Lu, C Chen, Z Yu, P AF Lu, Chi Chen, Zhi Yu, Ping TI A novel reaction model for the electrical conductivity of ultra-thin TiO2 films in H-2 SO PHYSICAL CHEMISTRY CHEMICAL PHYSICS LA English DT Article ID METAL-SUPPORT INTERACTIONS; HYDROGEN SPILLOVER; ALUMINUM-OXIDE; CATALYSTS; TITANIA; OXIDATION AB Two ultra-thin TiO2 films with platinum electrodes were prepared on a porous anodic aluminium oxide thick layer and a ceramic plate, respectively. It was found that in both TiO2 films the conductance was almost proportional to the fourth root of the H-2 concentration in N-2 ambient at 500 degrees C. A quantitative model based on the spill-over mechanism is established to describe this novel correlation. C1 [Lu, Chi; Chen, Zhi] Univ Kentucky, Dept Elect & Comp Engn, Lexington, KY 40506 USA. [Lu, Chi; Chen, Zhi] Univ Kentucky, Ctr Nanoscale Sci & Engn, Lexington, KY 40506 USA. [Yu, Ping] NCI, Metab Branch, NIH, Bethesda, MD 20892 USA. RP Lu, C (reprint author), Univ Kentucky, Dept Elect & Comp Engn, Lexington, KY 40506 USA. EM chi_lu_uky@yahoo.com OI Chen, Zhi/0000-0002-4451-5626 FU Department of Energy [DE-FG26-04NT42171]; National Science Foundation of the USA [ECS-0609064] FX This work was supported in part by the Department of Energy (DE-FG26-04NT42171) and National Science Foundation (ECS-0609064) of the USA. We appreciate the editorial assistance of the NIH Fellows Editorial Board. NR 22 TC 4 Z9 4 U1 0 U2 7 PU ROYAL SOC CHEMISTRY PI CAMBRIDGE PA THOMAS GRAHAM HOUSE, SCIENCE PARK, MILTON RD, CAMBRIDGE CB4 0WF, CAMBS, ENGLAND SN 1463-9076 J9 PHYS CHEM CHEM PHYS JI Phys. Chem. Chem. Phys. PY 2011 VL 13 IS 20 BP 9131 EP 9133 DI 10.1039/c1cp20180h PG 3 WC Chemistry, Physical; Physics, Atomic, Molecular & Chemical SC Chemistry; Physics GA 759FA UT WOS:000290224900006 PM 21503315 ER PT J AU Swierczewska, M Lee, S Chen, XY AF Swierczewska, Magdalena Lee, Seulki Chen, Xiaoyuan TI The design and application of fluorophore-gold nanoparticle activatable probes SO PHYSICAL CHEMISTRY CHEMICAL PHYSICS LA English DT Article ID RESONANCE ENERGY-TRANSFER; IN-VIVO; QUANTUM DOTS; ENHANCED FLUORESCENCE; RHEUMATOID-ARTHRITIS; METALLIC NANOCAVITY; CONJUGATED POLYMERS; MOLECULAR BEACONS; CELLS; DECAY AB Fluorescence-based assays and detection techniques are among the most highly sensitive and popular biological tests for researchers. To match the needs of research and the clinic, detection limits and specificities need to improve, however. One mechanism is to decrease non-specific background signals, which is most efficiently done by increasing fluorescence quenching abilities. Reports in the literature of theoretical and experimental work have shown that metallic gold surfaces and nanoparticles are ultra-efficient fluorescence quenchers. Based on these findings, subsequent reports have described gold nanoparticle fluorescence-based activatable probes that were designed to increase fluorescence intensity based on a range of stimuli. In this way, these probes can detect and signify assorted biomarkers and changes in environmental conditions. In this review, we explore the various factors and theoretical models that affect gold nanoparticle fluorescence quenching, explore current uses of activatable probes, and propose an engineering approach for future development of fluorescence based gold nanoparticle activatable probes. C1 [Swierczewska, Magdalena; Lee, Seulki; Chen, Xiaoyuan] NIBIB, NIH, LOMIN, Bethesda, MD 20892 USA. [Swierczewska, Magdalena] SUNY Stony Brook, Dept Biomed Engn, Stony Brook, NY 11794 USA. RP Lee, S (reprint author), NIBIB, NIH, LOMIN, Bethesda, MD 20892 USA. EM Seulki.Lee@nih.gov; Shawn.Chen@nih.gov FU National Institute of Biomedical Imaging and Bioengineering (NIBIB); NIH; National Science Foundation of China (NSFC) [81028009] FX This work was supported in part by the Intramural Research Program (IRP) of the National Institute of Biomedical Imaging and Bioengineering (NIBIB), NIH and the International Cooperative Program of the National Science Foundation of China (NSFC) (81028009). We thank Dr Henry S. Eden for proofreading the manuscript. NR 74 TC 72 Z9 72 U1 8 U2 60 PU ROYAL SOC CHEMISTRY PI CAMBRIDGE PA THOMAS GRAHAM HOUSE, SCIENCE PARK, MILTON RD, CAMBRIDGE CB4 0WF, CAMBS, ENGLAND SN 1463-9076 J9 PHYS CHEM CHEM PHYS JI Phys. Chem. Chem. Phys. PY 2011 VL 13 IS 21 BP 9929 EP 9941 DI 10.1039/c0cp02967j PG 13 WC Chemistry, Physical; Physics, Atomic, Molecular & Chemical SC Chemistry; Physics GA 765TR UT WOS:000290732000003 PM 21380462 ER PT J AU Revilla-Lopez, G Torras, J Nussinov, R Aleman, C Zanuy, D AF Revilla-Lopez, Guillem Torras, Juan Nussinov, Ruth Aleman, Carlos Zanuy, David TI Exploring the energy landscape of a molecular engineered analog of a tumor-homing peptide SO PHYSICAL CHEMISTRY CHEMICAL PHYSICS LA English DT Article ID CONFORMATIONAL PREFERENCES; AMINO-ACIDS; SOLVATION MODEL; SIDE-CHAIN; DYNAMICS; PROTEINS; DESIGN; PENTAPEPTIDE; SIMULATIONS; PACLITAXEL AB Recently a new non-coded amino acid was designed as a replacement for Arg, to protect the tumor-homing pentapeptide CREKA (Cys-Arg-Glu-Lys-Ala) from proteases. This constrained Arg analog, denoted c(5)Arg, was engineered to also promote the stability of the CREKA bioactive conformation. The conformational profile of the CREKA analog obtained by replacing Arg by c(5)Arg has been extensively investigated in this work. Two molecular dynamics simulations-based strategies have been employed: a modified simulated annealing and replica exchange. Results obtained using both techniques show that the conformational features of the new analog fulfill the purpose of its design. The new CREKA analog not only preserves the main structural attributes found for the bioactive conformation of the parent peptide but also shows lower flexibility. Moreover, the conformational profile of the mutated peptide narrows towards the most stable structures previously observed for the parent CREKA peptide. C1 [Revilla-Lopez, Guillem; Aleman, Carlos; Zanuy, David] Univ Politecn Cataluna, Dept Engn Quim, ETS Engn Ind Barcelona, E-08028 Barcelona, Spain. [Torras, Juan] Univ Politecn Cataluna, EEI, Dept Engn Quim, Igualada 08700, Spain. [Nussinov, Ruth] NCI, Ctr Canc Res, Nanobiol Program, Basic Sci Program,SAIC Frederick Inc, Frederick, MD 21702 USA. [Nussinov, Ruth] Tel Aviv Univ, Sch Med, Dept Human Genet Sackler, IL-69978 Tel Aviv, Israel. [Aleman, Carlos] Univ Politecn Cataluna, Ctr Res Nanoengn, E-08028 Barcelona, Spain. RP Zanuy, D (reprint author), Univ Politecn Cataluna, Dept Engn Quim, ETS Engn Ind Barcelona, Diagonal 647, E-08028 Barcelona, Spain. EM joan.torras@upc.edu; david.zanuy@upc.edu RI Revilla-Lopez, Guillem/G-8552-2011; Zanuy, David/G-3930-2014; Torras, Juan/F-5622-2015 OI Zanuy, David/0000-0001-7704-2178; Torras, Juan/0000-0001-8737-7609 FU Generalitat de Catalunya [SGR 925]; National Cancer Institute, National Institutes of Health [HHSN261200800001E]; NIH, National Cancer Institute, Center for Cancer Research FX Computer resources were generously provided by the Centre de Supercomputacio de Catalunya (CESCA), the National Cancer Institute for partial allocation of computing time and staff support at the Advanced Biomedical Computing Center of the Frederick Cancer Research and Development Center and the high-performance computational capabilities of the Biowulf PC/Linux cluster at the National Institutes of Health, Bethesda, MD (http://biowulf.nih.gov). Financial support from Generalitat de Catalunya (research group 2009 SGR 925; XRQTC; ICREA Academia prize for excellence in research to C. A.) is gratefully acknowledged. This project has been funded in part with Federal funds from the National Cancer Institute, National Institutes of Health, under contract number HHSN261200800001E. The content of this publication does not necessarily reflect the view of the policies of the Department of Health and Human Services, nor does mention of trade names, commercial products, or organization imply endorsement by the U.S. Government. This research was supported [in part] by the Intramural Research Program of the NIH, National Cancer Institute, Center for Cancer Research. NR 40 TC 4 Z9 4 U1 1 U2 7 PU ROYAL SOC CHEMISTRY PI CAMBRIDGE PA THOMAS GRAHAM HOUSE, SCIENCE PARK, MILTON RD, CAMBRIDGE CB4 0WF, CAMBS, ENGLAND SN 1463-9076 J9 PHYS CHEM CHEM PHYS JI Phys. Chem. Chem. Phys. PY 2011 VL 13 IS 21 BP 9986 EP 9994 DI 10.1039/c0cp02572k PG 9 WC Chemistry, Physical; Physics, Atomic, Molecular & Chemical SC Chemistry; Physics GA 765TR UT WOS:000290732000009 PM 21258721 ER PT J AU Kaila, VRI Hummer, G AF Kaila, Ville R. I. Hummer, Gerhard TI Energetics and dynamics of proton transfer reactions along short water wires SO PHYSICAL CHEMISTRY CHEMICAL PHYSICS LA English DT Article ID CYTOCHROME-C-OXIDASE; COUPLED ELECTRON-TRANSFER; PARACOCCUS-DENITRIFICANS; MOLECULAR-DYNAMICS; RATE CONSTANTS; STRUCTURAL DETERMINANTS; CORRELATION-ENERGY; CARBON NANOTUBES; EXCESS PROTON; LIQUID WATER AB Proton transfer (pT) reactions in biochemical processes are often mediated by chains of hydrogen-bonded water molecules. We use hybrid density functional calculations to study pT along quasi one-dimensional water arrays that connect an imidazolium-imidazole proton donor-acceptor pair. We characterize the structures of intermediates and transition states, the energetics, and the dynamics of the pT reactions, including vibrational contributions to kinetic isotope effects. In molecular dynamics simulations of pT transition paths, we find that for short water chains with four water molecules, the pT reactions are semi-concerted. The formation of a high-energy hydronium intermediate next to the proton-donating group is avoided by a simultaneous transfer of a proton from the donor to the first water molecule, and from the first water molecule into the water chain. Lowering the dielectric constant of the environment and increasing the water chain length both reduce the barrier for pT. We study the effect of the driving force on the energetics of the pT reaction by changing the proton affinity of the donor and acceptor groups through halogen and methyl substitutions. We find that the barrier of the pT reaction depends linearly on the proton affinity of the donor but is nearly independent of the proton affinity of the acceptor, corresponding to Bronsted slopes of one and zero, respectively. C1 [Kaila, Ville R. I.; Hummer, Gerhard] NIDDK, Chem Phys Lab, NIH, Bethesda, MD 20892 USA. RP Kaila, VRI (reprint author), NIDDK, Chem Phys Lab, NIH, 5 Mem Dr, Bethesda, MD 20892 USA. EM ville.kaila@nih.gov; gerhard.hummer@nih.gov RI Hummer, Gerhard/A-2546-2013 OI Hummer, Gerhard/0000-0001-7768-746X FU National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health; European Molecular Biology Organization (EMBO) FX We thank Dr. Jurgen Kofinger and Prof. Marten Wikstrom for insightful discussions. This research was supported by the Intramural Research Program of the National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health. V. R. I. K. also acknowledges the European Molecular Biology Organization (EMBO) for a Long-Term Fellowship. CSC, the Finnish IT Center for Science, and Biowulf cluster at NIH are acknowledged for computer time. NR 88 TC 20 Z9 21 U1 0 U2 31 PU ROYAL SOC CHEMISTRY PI CAMBRIDGE PA THOMAS GRAHAM HOUSE, SCIENCE PARK, MILTON RD, CAMBRIDGE CB4 0WF, CAMBS, ENGLAND SN 1463-9076 J9 PHYS CHEM CHEM PHYS JI Phys. Chem. Chem. Phys. PY 2011 VL 13 IS 29 BP 13207 EP 13215 DI 10.1039/c1cp21112a PG 9 WC Chemistry, Physical; Physics, Atomic, Molecular & Chemical SC Chemistry; Physics GA 795NT UT WOS:000292981600010 PM 21701719 ER PT J AU Kofinger, J Hummer, G Dellago, C AF Koefinger, Juergen Hummer, Gerhard Dellago, Christoph TI Single-file water in nanopores SO PHYSICAL CHEMISTRY CHEMICAL PHYSICS LA English DT Article ID BORON-NITRIDE NANOTUBES; MOLECULAR-DYNAMICS SIMULATIONS; SOLID-STATE NANOPORES; CARBON NANOTUBES; PROTON TRANSPORT; LIQUID WATER; ORIENTATIONAL DEFECTS; GRAMICIDIN CHANNEL; HYDRATED PROTON; MASS-TRANSPORT AB Water molecules confined to pores with sub-nanometre diameters form single-file hydrogen-bonded chains. In such nanoscale confinement, water has unusual physical properties that are exploited in biology and hold promise for a wide range of biomimetic and nanotechnological applications. The latter can be realized by carbon and boron nitride nanotubes which confine water in a relatively non-specific way and lend themselves to the study of intrinsic properties of single-file water. As a consequence of strong water-water hydrogen bonds, many characteristics of single-file water are conserved in biological and synthetic pores despite differences in their atomistic structures. Charge transport and orientational order in water chains depend sensitively on and are mainly determined by electrostatic effects. Thus, mimicking functions of biological pores with apolar pores and corresponding external fields gives insight into the structure-function relation of biological pores and allows the development of technical applications beyond the molecular devices found in living systems. In this Perspective, we revisit results for single-file water in apolar pores, and examine the similarities and the differences between these simple systems and water in more complex pores. C1 [Dellago, Christoph] Univ Vienna, Fac Phys, A-1090 Vienna, Austria. [Dellago, Christoph] Univ Vienna, Ctr Computat Mat Sci, A-1090 Vienna, Austria. [Koefinger, Juergen; Hummer, Gerhard] NIDDKD, Chem Phys Lab, NIH, Bethesda, MD 20892 USA. RP Dellago, C (reprint author), Univ Vienna, Fac Phys, Boltzmanngasse 5, A-1090 Vienna, Austria. RI Hummer, Gerhard/A-2546-2013 OI Hummer, Gerhard/0000-0001-7768-746X FU National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health; Austrian Science Foundation (FWF) [SFB ViCoM (F 41)] FX J.K. and G.H. were supported by the Intramural Research Program of the National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health. C.D. gratefully acknowledges financial support by the Austrian Science Foundation (FWF) within the SFB ViCoM (F 41). NR 160 TC 43 Z9 44 U1 7 U2 71 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 2011 VL 13 IS 34 BP 15403 EP 15417 DI 10.1039/c1cp21086f PG 15 WC Chemistry, Physical; Physics, Atomic, Molecular & Chemical SC Chemistry; Physics GA 807LT UT WOS:000293900400003 PM 21779552 ER PT J AU Best, RB Hummer, G AF Best, Robert B. Hummer, Gerhard TI Diffusion models of protein folding SO PHYSICAL CHEMISTRY CHEMICAL PHYSICS LA English DT Article ID BETA-HAIRPIN FORMATION; SINGLE-MOLECULE FRET; FREE-ENERGY; SPEED LIMIT; NONNATIVE INTERACTIONS; DEPENDENT DIFFUSION; REACTION COORDINATE; TRANSITION-STATES; REACTION DYNAMICS; EXPLICIT-SOLVENT AB In theory and in the analysis of experiments, protein folding is often described as diffusion along a single coordinate. We explore here the application of a one-dimensional diffusion model to interpret simulations of protein folding, where the parameters of a model that "best" describes the simulation trajectories are determined using a Bayesian analysis. We discuss the requirements for such a model to be a good approximation to the global dynamics, and several methods for testing its accuracy. For example, one test considers the effect of an added bias potential on the fitted free energies and diffusion coefficients. Such a bias may also be used to extend our approach to determining parameters for the model to systems that would not normally explore the full coordinate range on accessible time scales. Alternatively, the propagators predicted from the model at different "lag" times may be compared with observations from simulation. We then present some applications of the model to protein folding, including Kramers-like turnover in folding rates of coarse-grained models, the effect of non-native interactions on folding, and the effect of the chosen coordinate on the observed position-dependence of the diffusion coefficients. Lastly, we consider how our results are useful for the interpretation of experiments, and how this type of Bayesian analysis may eventually be applied directly to analyse experimental data. C1 [Best, Robert B.] Univ Cambridge, Dept Chem, Cambridge CB2 1EW, England. [Hummer, Gerhard] NIDDK, Chem Phys Lab, NIH, Bethesda, MD 20892 USA. RP Best, RB (reprint author), Univ Cambridge, Dept Chem, Lensfield Rd, Cambridge CB2 1EW, England. EM rbb24@cam.ac.uk; gerhard.hummer@nih.gov RI Hummer, Gerhard/A-2546-2013; Best, Robert/H-7588-2016 OI Hummer, Gerhard/0000-0001-7768-746X; Best, Robert/0000-0002-7893-3543 FU Royal Society; National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health FX R.B. is supported by a Royal Society University Research Fellowship. G.H. is supported by the Intramural Research Program of the National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health. NR 64 TC 29 Z9 29 U1 3 U2 38 PU ROYAL SOC CHEMISTRY PI CAMBRIDGE PA THOMAS GRAHAM HOUSE, SCIENCE PARK, MILTON RD, CAMBRIDGE CB4 0WF, CAMBS, ENGLAND SN 1463-9076 J9 PHYS CHEM CHEM PHYS JI Phys. Chem. Chem. Phys. PY 2011 VL 13 IS 38 BP 16902 EP 16911 DI 10.1039/c1cp21541h PG 10 WC Chemistry, Physical; Physics, Atomic, Molecular & Chemical SC Chemistry; Physics GA 823NC UT WOS:000295128000002 PM 21842082 ER PT J AU McGlinchey, RP Yap, TL Lee, JC AF McGlinchey, Ryan P. Thai Leong Yap Lee, Jennifer C. TI The yin and yang of amyloid: insights from alpha-synuclein and repeat domain of Pmel17 SO PHYSICAL CHEMISTRY CHEMICAL PHYSICS LA English DT Article ID MATRIX PROTEIN PMEL17/GP100; PINK-EYED DILUTION; SOLID-STATE NMR; PARKINSONS-DISEASE; LEWY-BODY; IN-VITRO; TRYPTOPHAN FLUORESCENCE; ELECTRON-TRANSFER; CONTACT DYNAMICS; FIBRIL STRUCTURE AB Amyloid has been traditionally viewed in the context of disease. However, the emerging concept of 'functional amyloid' has taken a new direction into how we view amyloid. Recent studies have identified amyloid fibrils ranging from bacteria to humans that have a beneficial role, instead of being associated with a misfolded state that has been implicated in diseases such as Alzheimer's, Parkinson's and prion diseases. Here, we review our work on two human amyloidogenic polypeptides, one associated with Parkinson's disease, alpha-synuclein (alpha-syn), and the other important for melanin synthesis, the repeat domain (RPT) from Pmel17. Particularly, we focused our attention on spectroscopic studies of protein conformation and dynamics and their impact on alpha-syn amyloid formation and for RPT, we discussed the strict pH dependence of amyloid formation and its role in melanin biosynthesis. C1 [McGlinchey, Ryan P.; Thai Leong Yap; Lee, Jennifer C.] NHLBI, Lab Mol Biophys, 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 National Institutes of Health, National Heart, Lung, and Blood Institute FX This work was supported by the Intramural Research Program at the National Institutes of Health, National Heart, Lung, and Blood Institute. We thank Rob Tycko in providing the A beta amyloid structure and Candace Pfefferkorn for discussion. NR 103 TC 12 Z9 12 U1 1 U2 10 PU ROYAL SOC CHEMISTRY PI CAMBRIDGE PA THOMAS GRAHAM HOUSE, SCIENCE PARK, MILTON RD, CAMBRIDGE CB4 0WF, CAMBS, ENGLAND SN 1463-9076 J9 PHYS CHEM CHEM PHYS JI Phys. Chem. Chem. Phys. PY 2011 VL 13 IS 45 BP 20066 EP 20075 DI 10.1039/c1cp21376h PG 10 WC Chemistry, Physical; Physics, Atomic, Molecular & Chemical SC Chemistry; Physics GA 846BF UT WOS:000296871500003 PM 21993592 ER PT J AU Cintas, HL Parks, R Don, S Gerber, L AF Cintas, Holly Lea Parks, Rebecca Don, Sarah Gerber, Lynn TI Brief Assessment of Motor Function: Content Validity and Reliability of the Upper Extremity Gross Motor Scale SO PHYSICAL & OCCUPATIONAL THERAPY IN PEDIATRICS LA English DT Article DE Evidence-based practice; knowledge translation; mobility; motor development ID SUPINE POSITION; ERECT STANCE; MOVEMENT; INFANT; RISE AB Content validity and reliability of the Brief Assessment of Motor Function (BAMF) Upper Extremity Gross Motor Scale (UEGMS) were evaluated in this prospective, descriptive study. The UEGMS is one of five BAMF ordinal scales designed for quick documentation of gross, fine, and oral motor skill levels. Designed to be independent of age and diagnosis, it is intended for use for infants through young adults. An expert panel of 17 physical therapists and 13 occupational therapists refined the content by responding to a standard questionnaire comprised of questions, which asked whether each item should be included, is clearly worded, should be reordered higher or lower, is functionally relevant, and is easily discriminated. Ratings of content validity exceeded the criterion except for two items, which may represent different perspectives of physical and occupational therapists. The UEGMS was modified using the quantitative and qualitative feedback from the questionnaires. For reliability, five raters scored videotaped motor performances of 10 children. Coefficients for inter-rater (0.94) and intra-rater (0.95) reliability were high. The results provide evidence of content validity and reliability of the UEGMS for the assessment of UEGM skill. C1 [Cintas, Holly Lea] NIH, Phys Therapy Sect, Dept Rehabil Med, Mark O Hatfield Clin Res Ctr, Bethesda, MD 20892 USA. [Don, Sarah] Envoy Rehabil Ctr, Occupat Therapy Dept, Pikesville, MD USA. [Gerber, Lynn] George Mason Univ, Ctr Chron Illness & Disabil, Fairfax, VA 22030 USA. RP Cintas, HL (reprint author), NIH, Phys Therapy Sect, Dept Rehabil Med, Mark O Hatfield Clin Res Ctr, Bldg 10 CRC,Room 1-1469 NE, Bethesda, MD 20892 USA. EM holly_cintas@nih.gov FU NIH FX We would like to acknowledge the valuable advice and direction provided by Gloria Furst, OTR/L, MPH, Consultant, Rehabilitation Medicine Department, NIH. We also would like to thank the parents and their children who participated in the reliability study, and the physical therapists, occupational therapists, and the physical and occupational therapy students who shared their time and expertise to complete the content validity and reliability studies. The NIH Intramural Research Program funded this study. NR 24 TC 1 Z9 1 U1 0 U2 1 PU INFORMA HEALTHCARE PI LONDON PA TELEPHONE HOUSE, 69-77 PAUL STREET, LONDON EC2A 4LQ, ENGLAND SN 0194-2638 J9 PHYS OCCUP THER PEDI JI Phys. Occup. Ther. Pediatr. PY 2011 VL 31 IS 4 BP 440 EP 450 DI 10.3109/01942638.2011.572148 PG 11 WC Pediatrics; Rehabilitation SC Pediatrics; Rehabilitation GA 833NT UT WOS:000295892900008 PM 21599568 ER PT J AU Andjus, PR Stojilkovic, SS Cvijic, G AF Andjus, P. R. Stojilkovic, S. S. Cvijic, G. TI Ivan Djaja (Jean Giaja) and the Belgrade School of Physiology SO PHYSIOLOGICAL RESEARCH LA English DT Article DE History of physiology; Sorbonne; University of Belgrade; Bioenergetics; Thermoregulation; Neuroendocrine regulation ID SQUIRREL CITELLUS-CITELLUS; DEVELOPMENTAL PATTERN; MALE-RAT; PROFONDE HYPOTHERMIE; BODY TEMPERATURES; LH LEVELS; ANDROGEN; REANIMATION AB The founder of physiology studies in the Balkans and the pioneer of research on hypothermia, Ivan Djaja (Jean Giaja) was born 1884 in L'Havre. Giaja gained his PhD at the Sorbonne in 1909. In 1910 he established the first Chair of Physiology in the Balkans and organized the first Serbian Institute for Physiology at the School of Philosophy of the University of Belgrade. He led this Institute for more than 40 subsequent years. His most notable papers were in the field of thermoregulation and bioenergetics. Djaja became member of the Serbian and Croatian academies of science and doctor honoris causa of Sorbonne. In 1952 for the seminal work on the behavior of deep cooled warm blooded animals he became associate member of the National Medical Academy in Paris. In 1955 the French Academy of Sciences elected him as associate member in place of deceased Sir Alexander Fleming. Djaja died in 1957 during a congress held in his honor. He left more than 200 scientific and other papers and the golden DaVincian credo "Nulla dies sine experimento". His legacy was continued by several generations of researchers, the most prominent among them being Stefan Gelineo, Radoslav Andjus and Vojislav Petrovic. C1 [Andjus, P. R.; Cvijic, G.] Univ Belgrade, Inst Physiol & Biochem, Fac Biol, Belgrade 11000, Serbia. [Stojilkovic, S. S.] NICHHD, Sect Cellular Signaling, Program Dev Neurosci, NIH, Bethesda, MD 20892 USA. RP Andjus, PR (reprint author), Univ Belgrade, Inst Physiol & Biochem, Fac Biol, Belgrade 11000, Serbia. EM pandjus@bio.bg.ac.rs FU Intramural NIH HHS [Z01 HD000195-15] NR 40 TC 1 Z9 1 U1 0 U2 2 PU ACAD SCIENCES CZECH REPUBLIC, INST PHYSIOLOGY PI PRAGUE 4 PA VIDENSKA 1083, PRAGUE 4 142 20, CZECH REPUBLIC SN 0862-8408 J9 PHYSIOL RES JI Physiol. Res. PY 2011 VL 60 SU 1 BP S1 EP S13 PG 13 WC Physiology SC Physiology GA 838ZT UT WOS:000296334200001 PM 21777022 ER PT J AU Mansky, PJ Wallerstedt, DB Sannes, T Stagl, J Johnson, LL Blackman, MR Grem, JL Swain, SM Schlodder, D Monahan, BP AF Mansky, P. J. Wallerstedt, D. B. Sannes, T. Stagl, J. Johnson, L. L. Blackman, M. R. Grem, J. L. Swain, S. M. Schlodder, D. Monahan, B. P. TI NCCAM/NCI phase 1 study of mistletoe extract and Gemcitabine in patients with advanced solid tumors SO PHYTOMEDICINE LA English DT Meeting Abstract DE Mistletoe; Safety and toxicity; Phase I trial C1 [Mansky, P. J.] Bellin Hlth, Green Bay, WI USA. [Mansky, P. J.; Wallerstedt, D. B.; Sannes, T.; Stagl, J.; Johnson, L. L.] Natl Ctr Complementary & Alternat Med, NIH, Bethesda, MD USA. [Blackman, M. R.] Vet Affairs Med Ctr, Res Serv, Washington, DC 20422 USA. [Grem, J. L.] Univ Nebraska Medcl Ctr, Omaha, NE USA. [Swain, S. M.] Washington Hosp Ctr, Washington, DC 20010 USA. [Schlodder, D.] Helixor Heilmittel GmbH & Co KG, Rosenfeld, Germany. [Monahan, B. P.] Congress US, Washington, DC USA. EM manpaj@bellin.org NR 0 TC 0 Z9 0 U1 0 U2 1 PU ELSEVIER GMBH, URBAN & FISCHER VERLAG PI JENA PA OFFICE JENA, P O BOX 100537, 07705 JENA, GERMANY SN 0944-7113 J9 PHYTOMEDICINE JI Phytomedicine PY 2011 VL 18 SU 8 BP S12 EP S12 DI 10.1016/j.phymed.2011.09.029 PG 1 WC Plant Sciences; Chemistry, Medicinal; Integrative & Complementary Medicine; Pharmacology & Pharmacy SC Plant Sciences; Pharmacology & Pharmacy; Integrative & Complementary Medicine GA 850ID UT WOS:000297187400023 ER PT J AU White, JG Gunay-Aygun, M AF White, James G. Gunay-Aygun, Meral TI The York Platelet Syndrome: A third case SO PLATELETS LA English DT Article ID ELECTRON-DENSE CHAINS; INHERITED THROMBOCYTOPENIC DISORDER; MEGAKARYOCYTES; CLUSTERS; GRANULES; BODIES AB Our present study has described a third patient with the York Platelet Syndrome (YPS). The condition consists of a mitochondrial myopathy associated with unique platelet pathology. Their mitochondrial myopathy has not been completely delineated and will be the subject of further study. Platelet pathology in the new patient is essentially identical to that described in the first two patients. Thin sections of her thrombocytes reveal a normal complement of alpha alpha and delta delta granules (dense bodies) in some, a decreased number in others and complete absence in a few. The unique pathological feature is the presence of giant organelles, including an intensely electron dense, huge body, the opaque organelle (OO) and a multilayered large body, the target organelle. In addition platelets from the new patient contain large masses and coils of smooth endoplasmic reticulum present infrequently in platelets of the first two patients. The giant opaque and target organelles appear to develop in rough and smooth endoplasmic reticulum of the parent megakaryocyte and mature in the dense tubular system of circulating platelets. The relationship of the unique platelet pathology and mitochondrial myopathy has not been defined.= 3 g/dL and/or >= 10% clonal bone marrow plasma cells, in the absence of end-organ damage. Based on clinical observations, the natural history of SMM varies greatly, from stable, monoclonal gammopathy of undetermined significance (MGUS)-like disease to highly progressive disease. Using conventional clinical markers, SMM patients can be stratified into clinical risk groups. However, due to considerable molecular heterogeneity, we currently lack reliable markers to predict prognosis for individual SMM patients. Based on the International Myeloma Working Group 2010 guidelines, patients diagnosed with MGUS and SMM should not be treated outside of clinical trials. Overall, treatment trials for MGUS patients are complicated, as these individuals are relatively healthy and the majority has a low life-time risk of progression, especially when other causes of death are taken into account. In contrast to MGUS, early treatment strategies for SMM are particularly attractive, as the rate of progression to multiple myeloma is substantially higher. Until recently, potent drugs with reasonable toxicity profiles have not been available for the development of early multiple myeloma treatment strategies. This review discusses how the integration of novel biological markers and clinical monitoring of SMM could facilitate the development of early treatment strategies for high-risk SMM patients in the future. Semin Hematol 48:66-72. 2011 Published by Elsevier Inc. C1 [Landgren, Ola] NCI, NIH, Ctr Canc Res, Med Oncol Branch, Bethesda, MD 20892 USA. [Rajkumar, S. Vincent] Mayo Clin, Div Hematol, Rochester, MN USA. RP Landgren, O (reprint author), NCI, NIH, Ctr Canc Res, Med Oncol Branch, 9000 Rockville Pike,Bldg 10,Room 13N240, Bethesda, MD 20892 USA. EM landgreo@mail.nih.gov OI Rajkumar, S. Vincent/0000-0002-5862-1833 FU National Cancer Institute of the National Institutes of Health; National Cancer Institute [CA 62242, CA 107-476-03]; Division of Hematology at the Mayo Clinic, Rochester, MN; Division of Biostatistics at the Mayo Clinic, Rochester, MN; Division of Clinical Biochemistry at the Mayo Clinic, Rochester, MN; Division of Immunology at the Mayo Clinic, Rochester, MN FX This work was supported by the Intramural Research Program of the National Cancer Institute of the National Institutes of Health; grants no. CA 62242 and CA 107-476-03 from the National Cancer Institute; and the facilities and resources of the Divisions of Hematology, Biostatistics, Clinical Biochemistry and Immunology, and Epidemiology at the Mayo Clinic, Rochester, MN. NR 43 TC 4 Z9 4 U1 0 U2 1 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0037-1963 EI 1532-8686 J9 SEMIN HEMATOL JI Semin. Hematol. PD JAN PY 2011 VL 48 IS 1 BP 66 EP 72 DI 10.1053/j.seminhematol.2010.11.009 PG 7 WC Hematology SC Hematology GA 709AA UT WOS:000286406100009 PM 21232660 ER PT J AU Bouchelouche, K Tagawa, ST Goldsmith, SJ Turkbey, B Capala, J Choyke, P AF Bouchelouche, Kirsten Tagawa, Scott T. Goldsmith, Stanley J. Turkbey, Bans Capala, Jacek Choyke, Peter TI PET/CT Imaging and Radioimmunotherapy of Prostate Cancer SO SEMINARS IN NUCLEAR MEDICINE LA English DT Article; Proceedings Paper CT 14th International Symposium on Radionuclides in Nephrourology CY MAY 11-14, 2010 CL Mikulov, CZECH REPUBLIC ID POSITRON-EMISSION-TOMOGRAPHY; TOSITUMOMAB/IODINE I-131 TOSITUMOMAB; COMBINED-MODALITY RADIOIMMUNOTHERAPY; MITOXANTRONE PLUS PREDNISONE; MONOCLONAL-ANTIBODY J591; LYMPH-NODE METASTASES; NON-HODGKIN-LYMPHOMA; GROUP PROTOCOL S9911; PHASE-I TRIAL; RADICAL PROSTATECTOMY AB Prostate cancer is a common cancer in men and continues to be a major health problem. Imaging plays an important role in the clinical management of patients with prostate cancer. An important goal for prostate cancer imaging is more accurate disease characterization through the synthesis of anatomic, functional, and molecular imaging information. Positron emission tomography (PET)/computed tomography (CT) in oncology is emerging as an important imaging tool. The most common radiotracer for PET/CT in oncology, F-18-fluorodeoxyglucose (FDG), is not very useful in the imaging of prostate cancer. However, in recent years other PET tracers have improved the accuracy of PET/CT imaging of prostate cancer. Among these, choline labeled with F-18 or C-11, C-11-acetate, and F-18-fluoride has demonstrated promising results, and other new radiopharmaceuticals are under development and evaluation in preclinical and clinical studies. Large prospective clinical PET/CT trials are needed to establish the role of PET/CT in prostate cancer patients. Because there are only limited available therapeutic options for patients with advanced metastatic prostate cancer, there is an urgent need for the development of more effective treatment modalities that could improve outcome. Prostate cancer represents an attractive target for radioimmunotherapy (RIT) for several reasons, including pattern of metastatic spread (lymph nodes and bone marrow, sites with good access to circulating antibodies) and small volume disease (ideal for antigen access and antibody delivery). Furthermore, prostate cancer is also radiation sensitive. Prostate-specific membrane antigen is expressed by virtually all prostate cancers, and represents an attractive target for RIT. Antiprostate-specific membrane antigen RIT demonstrates antitumor activity and is well tolerated. Clinical trials are underway to further improve upon treatment efficacy and patient selection. This review focuses on the recent advances of clinical PET/CT imaging and RIT of prostate cancer. Semin Nucl Med 41:29-44 (C) 2011 Elsevier Inc. All rights reserved. C1 [Bouchelouche, Kirsten] Univ Copenhagen, Rigshosp, PET 3982, PET & Cyclotron Unit, DK-2100 Copenhagen, Denmark. [Tagawa, Scott T.] Weill Cornell Med Coll, Div Hematol & Med Oncol, New York, NY USA. [Goldsmith, Stanley J.] New York Presbyterian Hosp, Weill Cornell Med Ctr, Dept Radiol, Div Nucl Med & Mol Imaging, New York, NY USA. [Turkbey, Bans; Choyke, Peter] NCI, Mol Imaging Program, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. [Capala, Jacek] NCI, Mol Targeting Sect, Radiat Oncol Branch, Ctr Canc Res,NIH, Bethesda, MD 20892 USA. RP Bouchelouche, K (reprint author), Univ Copenhagen, Rigshosp, PET 3982, PET & Cyclotron Unit, Blegdamsvej 9, DK-2100 Copenhagen, Denmark. EM bouchelouche@mail.tele.dk FU Intramural NIH HHS [ZIA BC010727-04] NR 159 TC 38 Z9 41 U1 1 U2 10 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0001-2998 EI 1558-4623 J9 SEMIN NUCL MED JI Semin. Nucl. Med. PD JAN PY 2011 VL 41 IS 1 BP 29 EP 44 DI 10.1053/j.semnuclmed.2010.08.005 PG 16 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 694GT UT WOS:000285283700005 PM 21111858 ER PT J AU Raghuveer, K Senthilkumaran, B Sudhakumari, CC Sridevi, P Rajakumar, A Singh, R Murugananthkumar, R Majumdar, KC AF Raghuveer, K. Senthilkumaran, B. Sudhakumari, C. C. Sridevi, P. Rajakumar, A. Singh, R. Murugananthkumar, R. Majumdar, K. C. TI Dimorphic Expression of Various Transcription Factor and Steroidogenic Enzyme Genes during Gonadal Ontogeny in the Air-Breathing Catfish, Clarias gariepinus SO SEXUAL DEVELOPMENT LA English DT Article DE Catfish; Dimorphic expression; Gonadal development; Ovary; Sex differentiation; Teleosts; Testis ID TILAPIA OREOCHROMIS-NILOTICUS; SEX-DIFFERENTIATION; TELEOST FISH; NILE TILAPIA; DMRT1 EXPRESSION; ORYZIAS-LATIPES; MEDAKA; SOX9; REVERSAL; DEHYDROGENASE AB In the present study the expression of 13 genes known to be involved in sex differentiation and steroidogenesis in catfish was analyzed during gonadal ontogeny by quantitative real-time RT-PCR. Dmrt1 and sox9a showed exclusive expression in male gonads while ovarian aromatase (cyp19a1) and foxl2 were abundant in differentiating female gonads. Most of the genes related to steroidogenesis were expressed only after gonadal differentiation. However, genes coding for 3 beta-hydroxysteroid dehydrogenase (3 beta-hsd), 17 alpha-hydroxylase/C17-20 lyase type 1 (cyp17) and steroidogenic acute regulatory protein (star) were barely detectable during gonadal differentiation. Ovarian aromatase, cyp19a1, which is responsible for estradiol-17 beta biosynthesis in females, was expressed very early in the undifferentiated gonads of catfish, around 30-40 days post hatch (dph). The steroidogenic enzyme, 11 beta-hydroxylase (cyp11b1) required for the production of 11-ketotestosterone (11-KT) was expressed only after differentiation of testis. These results suggest that estradiol-17 beta has a critical role in ovarian differentiation, while the role of 11-KT in testicular differentiation is doubtful. In conclusion, dimorphic expression of dmrt1 and sox9a in gonads during early development is required for testicular differentiation, and sex-specific expression of cyp19a1 and foxl2 in females plays a critical role in ovarian development. Our study reveals that the critical period of gonadal differentiation in catfish starts around 30-40 dph when sex-specific genes showed differential expression. Copyright (C) 2011 S. Karger AG, Basel C1 [Raghuveer, K.; Senthilkumaran, B.; Sudhakumari, C. C.; Sridevi, P.; Rajakumar, A.; Singh, R.; Murugananthkumar, R.] Univ Hyderabad, Dept Anim Sci, Sch Life Sci, Ctr Adv Studies, Hyderabad 500046, Andhra Pradesh, India. [Majumdar, K. C.] Ctr Cellular & Mol Biol, Hyderabad 500007, Andhra Pradesh, India. [Raghuveer, K.] NICHD, NIH, Bethesda, MD USA. RP Senthilkumaran, B (reprint author), Univ Hyderabad, Dept Anim Sci, Sch Life Sci, Ctr Adv Studies, PO Cent Univ, Hyderabad 500046, Andhra Pradesh, India. EM bsksl@uohyd.ernet.in RI Perez , Claudio Alejandro/F-8310-2010 OI Perez , Claudio Alejandro/0000-0001-9688-184X FU University Grants Commission [34-412/2008]; University of Hyderabad (UH), India; Council of Scientific and Industrial Research/University Grant Commission; DBT-CREBB, India FX A Grant-in-Aid from the University Grants Commission (F. No. 34-412/2008) awarded to B. S. and a DST-PURSE grant from the University of Hyderabad (UH), India supported this work. K. R., P. S., R. S. and R. M. thank the Council of Scientific and Industrial Research/University Grant Commission for junior/senior research fellowship. We thank our Vice-Chancellor, Prof. Seyed E. Hasnain, and the Dean, Prof. M. Ramanadham, for allowing us to use the Genomics and Microarray facility of the School of Life Sciences, UH, partially sponsored by DBT-CREBB, India. All authors thank Prof. Yoshitaka Nagahama from the National Institute of Basic Biology, Okazaki, Japan for his generous gift of Cyp19a1 antiserum for our research. NR 43 TC 34 Z9 36 U1 1 U2 8 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 1661-5425 J9 SEX DEV JI Sex. Dev. PY 2011 VL 5 IS 4 BP 213 EP 223 DI 10.1159/000328823 PG 11 WC Developmental Biology SC Developmental Biology GA 800BO UT WOS:000293332400006 PM 21720151 ER PT J AU Falade-Nwulia, O Thio, CL AF Falade-Nwulia, Oluwaseun Thio, Chloe L. TI Liver disease, HIV and aging SO SEXUAL HEALTH LA English DT Article DE cirrhosis; hepatitis; highly active antiretroviral therapy ID HEPATITIS-C-VIRUS; HUMAN-IMMUNODEFICIENCY-VIRUS; ALPHA-2A PLUS RIBAVIRIN; ACTIVE ANTIRETROVIRAL THERAPY; INFECTED PATIENTS; B-VIRUS; HEPATOCELLULAR-CARCINOMA; UNITED-STATES; ELDERLY-PATIENTS; NATURAL-HISTORY AB The life expectancy of HIV-infected patients has increased due to the efficacy of highly active antiretroviral therapy (HAART) in controlling HIV replication; thus, the population living with HIV infection is steadily aging. Liver-related morbidity and mortality has emerged as a leading problem in HIV-infected patients. Since aging, HIV infection and HAART all affect the liver, understanding the impact of the combination of these factors on liver disease is crucial for optimisation of care in the aging HIV-infected population. This review will focus on the current understanding of liver disease in older (>50 years old) HIV-negative individuals and in HIV-infected individuals. Areas for future research in the area of HIV, liver disease and aging will also be discussed. C1 [Falade-Nwulia, Oluwaseun; Thio, Chloe L.] Johns Hopkins Univ, Sch Med, Div Infect Dis, Baltimore, MD 21231 USA. [Falade-Nwulia, Oluwaseun] NIH, Crit Care Med Dept, Bethesda, MD 20892 USA. RP Falade-Nwulia, O (reprint author), Johns Hopkins Univ, Sch Med, Div Infect Dis, 855 N Wolfe St,Suite 520, Baltimore, MD 21231 USA. EM faladeoo@cc.nih.gov FU NIH [AI060449, AI017820] FX CLT is supported by NIH grants AI060449 and AI017820. NR 89 TC 5 Z9 5 U1 0 U2 0 PU CSIRO PUBLISHING PI COLLINGWOOD PA 150 OXFORD ST, PO BOX 1139, COLLINGWOOD, VICTORIA 3066, AUSTRALIA SN 1448-5028 J9 SEX HEALTH JI Sex Health PY 2011 VL 8 IS 4 SI SI BP 512 EP 520 DI 10.1071/SH10163 PG 9 WC Public, Environmental & Occupational Health; Infectious Diseases SC Public, Environmental & Occupational Health; Infectious Diseases GA 844UM UT WOS:000296774000010 PM 22127037 ER PT B AU Farci, P AF Farci, Patrizia BE Dooley, JS Lok, AF Burroughs, AK Heathcote, EJ TI Hepatitis D SO SHERLOCK'S DISEASES OF THE LIVER AND BILIARY SYSTEM, 12TH EDITION LA English DT Article; Book Chapter ID CHRONIC DELTA-HEPATITIS; B SURFACE-ANTIGEN; INTERFERON-ALPHA TREATMENT; IMMUNODEFICIENCY-VIRUS-INFECTION; NORTHERN SOUTH-AMERICA; C-VIRUS; LIVER-DISEASE; PEGYLATED INTERFERON-ALPHA-2B; MAJOR CLADES; GENOTYPE-II C1 NIAID, Hepat Pathogenesis Sect, Infect Dis Lab, NIH, Bethesda, MD 20892 USA. RP Farci, P (reprint author), NIAID, Hepat Pathogenesis Sect, Infect Dis Lab, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA. NR 76 TC 1 Z9 1 U1 0 U2 0 PU BLACKWELL SCIENCE PUBL PI OXFORD PA OSNEY MEAD, OXFORD OX2 0EL, ENGLAND BN 978-1-4443-4126-3; 978-1-4051-3489-7 PY 2011 BP 393 EP 405 D2 10.1002/9781444341294 PG 13 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA BB8MA UT WOS:000346850500021 ER PT B AU Seeff, LB Fontana, RJ AF Seeff, Leonard B. Fontana, Robert J. BE Dooley, JS Lok, AF Burroughs, AK Heathcote, EJ TI Drug-Induced Liver Injury SO SHERLOCK'S DISEASES OF THE LIVER AND BILIARY SYSTEM, 12TH EDITION LA English DT Article; Book Chapter ID NONSTEROIDAL ANTIINFLAMMATORY DRUGS; INDUCED HEPATIC-INJURY; CHRONIC ACTIVE HEPATITIS; ENDOPLASMIC-RETICULUM AUTOANTIBODIES; DIHYDRALAZINE-INDUCED HEPATITIS; DICLOFENAC-INDUCED HEPATITIS; CAUSALITY ASSESSMENT METHOD; OF-THE-LITERATURE; SALT EXPORT PUMP; INDUCED HEPATOTOXICITY C1 [Seeff, Leonard B.] NIDDK, NIH, Bethesda, MD 20892 USA. [Fontana, Robert J.] Univ Michigan, Sch Med, Dept Internal Med, Div Gastroenterol, Ann Arbor, MI USA. NR 285 TC 0 Z9 0 U1 0 U2 1 PU BLACKWELL SCIENCE PUBL PI OXFORD PA OSNEY MEAD, OXFORD OX2 0EL, ENGLAND BN 978-1-4443-4126-3; 978-1-4051-3489-7 PY 2011 BP 478 EP 506 D2 10.1002/9781444341294 PG 29 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA BB8MA UT WOS:000346850500026 ER PT B AU Chen, Z AF Chen, Zhong BE Glick, AB VanWaes, C TI Aberrant Activation of HGF/c-MET Signaling and Targeted Therapy in Squamous Cancer SO SIGNALING PATHWAYS IN SQUAMOUS CANCER LA English DT Article; Book Chapter ID HEPATOCYTE GROWTH-FACTOR; RECEPTOR TYROSINE KINASE; COMPARATIVE GENOMIC HYBRIDIZATION; PAPILLARY RENAL-CARCINOMAS; TUMOR-STROMAL INTERACTIONS; CELLS IN-VITRO; FACTOR-KAPPA-B; C-MET; FACTOR/SCATTER FACTOR; SCATTER-FACTOR AB Aberrant activation of the c-MET signaling pathway has been identified in multiple carcinomas, including bladder, renal, cervical, colon, breast, ovary, lung, esophagus, gastric, and head and neck cancers The underlying genetic and functional abnormalities include gene amplification of c-MET/hepatocyte growth factor (HGF) gene loci, c-MET mutation, overexpression of c-MET and HGF due to transcriptional dysregulation or promoter polymorphisms, and autocrine or paracrine activation mediated by cytokines and growth factors HGF/c-MET signaling promotes an aggressive malignant phenotype, including increased cell proliferation and survival, epithelial-mesenchymal transition (EMT), invasion, angiogenesis and inflammation, and metastasis HGF and its coregulated proinflammatory and proangiogenic growth factors in serum, as well as c-MET mutation, amplification and phosphorylation in tumor specimens, have been identified as important indicators for patient prognosis and responses to therapies targeting HGF/c MET Targeting HGF/c-MET and related signaling pathways are important strategies in the development of anticancer drugs, and a panel of small molecule inhibitors and biological antagonists have been tested in clinical trials C1 Natl Inst Deafness & Other Commun Disorders, Head & Neck Surg Branch, NIH, Bethesda, MD 20892 USA. RP Chen, Z (reprint author), Natl Inst Deafness & Other Commun Disorders, Head & Neck Surg Branch, NIH, 10 Ctr Dr,Bldg 10,5D55, Bethesda, MD 20892 USA. NR 115 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013, UNITED STATES BN 978-1-4419-7202-6 PY 2011 BP 91 EP 111 DI 10.1007/978-1-4419-7203-3_4 D2 10.1007/978-1-4419-7203-3 PG 21 WC Oncology SC Oncology GA BSQ66 UT WOS:000285483600004 ER PT B AU Cataisson, C Yuspa, SH AF Cataisson, Christophe Yuspa, Stuart H. BE Glick, AB VanWaes, C TI Interacting Signaling Pathways in Mouse Skin Tumor Initiation and Progression SO SIGNALING PATHWAYS IN SQUAMOUS CANCER LA English DT Article; Book Chapter ID PROTEIN-KINASE-C; GROWTH-FACTOR RECEPTOR; NF-KAPPA-B; SQUAMOUS-CELL CARCINOMAS; NECROSIS-FACTOR-ALPHA; TRANSGENIC MICE; ONCOGENIC RAS; CHEMOKINE EXPRESSION; EPIDERMAL NEOPLASIA; HA-RAS AB The multistage induction of squamous cell cancer (SCC) on mouse skin as a consequence of chemical exposures has remarkable phenotypic and genotypic homology to human SCC development Genetically altered mouse models have been instrumental in defining the respective contribution of signaling pathways on the development of SCC in vivo Central to the skin carcinogenesis process is the activation of the EGFR Ras-MAPK pathway While hyperactivation of the pathway can often be attributed to activating mutations in ras genes, it appears that for the majority of cases the pathway is activated by alterations in upstream modulators as well as downstream effectors that are integral to the altered phenotype of the initiated keratinocytes This chapter will review data from experimental inductions of cutaneous SCC with a special emphasis on mouse models Particularly, the role of the EGFR-Ras-MAPK pathway, protein kinase C, nuclear factor kappa B and the expression of proinflammatory factors by transformed keratinocyte will be covered in more detail C1 [Cataisson, Christophe; Yuspa, Stuart H.] NCI, Lab Canc Biol & Genet, NIH, Bethesda, MD 20892 USA. RP Yuspa, SH (reprint author), NCI, Lab Canc Biol & Genet, NIH, Bethesda, MD 20892 USA. NR 96 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013, UNITED STATES BN 978-1-4419-7202-6 PY 2011 BP 149 EP 164 DI 10.1007/978-1-4419-7203-3_7 D2 10.1007/978-1-4419-7203-3 PG 16 WC Oncology SC Oncology GA BSQ66 UT WOS:000285483600007 ER PT B AU Peters, JM Gonzalez, FJ AF Peters, Jeffrey M. Gonzalez, Frank J. BE Glick, AB VanWaes, C TI Regulation of Squamous Cell Carcinoma Carcinogenesis by Peroxisome Proliferator-Activated Receptors SO SIGNALING PATHWAYS IN SQUAMOUS CANCER LA English DT Article; Book Chapter ID BETA/DELTA PPAR-BETA/DELTA; SMOOTH-MUSCLE-CELLS; NF-KAPPA-B; LIGAND ACTIVATION; DELTA AGONIST; MOUSE SKIN; KERATINOCYTE DIFFERENTIATION; GENE-EXPRESSION; INFLAMMATORY RESPONSE; COLON CARCINOGENESIS AB Peroxisome proliferator-activated receptors (PPARs) are nuclear receptors that respond to endogenous and exogenous signaling molecules and modulate cellular functions PPARs regulate many target genes that in turn influence cell growth, differentiation, and inflammatory signaling These changes can occur through direct transcriptional up-regulation of target genes, through secondary changes subsequent to direct transcriptional up regulation of target genes, and through protein-protein interactions The focus of this chapter is to summarize PPAR-dependent regulation of cellular signaling in squamous epithelium, and how these changes influence cancer C1 [Peters, Jeffrey M.] Penn State Univ, Ctr Mol Toxicol & Carcinogenesis, Dept Vet & Biomed Sci, University Pk, PA 16802 USA. [Gonzalez, Frank J.] NCI, Lab Metab, Bethesda, MD 20892 USA. RP Peters, JM (reprint author), Penn State Univ, Ctr Mol Toxicol & Carcinogenesis, Dept Vet & Biomed Sci, University Pk, PA 16802 USA. NR 105 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013, UNITED STATES BN 978-1-4419-7202-6 PY 2011 BP 223 EP 240 DI 10.1007/978-1-4419-7203-3_11 D2 10.1007/978-1-4419-7203-3 PG 18 WC Oncology SC Oncology GA BSQ66 UT WOS:000285483600011 ER PT B AU Amornphimoltham, P Patel, V Molinolo, A Gutkind, JS AF Amornphimoltham, Panomwat Patel, Vyomesh Molinolo, Alfredo Gutkind, J. Silvio BE Glick, AB VanWaes, C TI Head and Neck Cancer and the PI3K/Akt/mTOR Signaling Network: Novel Molecular Targeted Therapies SO SIGNALING PATHWAYS IN SQUAMOUS CANCER LA English DT Article; Book Chapter ID SQUAMOUS-CELL CARCINOMA; RICTOR-MTOR COMPLEX; MAMMALIAN TARGET; ORAL CARCINOGENESIS; HUMAN-DISEASE; PHASE-II; KINASE-B; RAPAMYCIN; PATHWAY; PHOSPHORYLATION AB Head and neck squamous cell carcinoma (HNSCC) represents the sixth most common cancer among men worldwide Despite significant advances in conventional therapies for other prevalent cancer types, the survival rate of HNSCC patients has barely improved over the past 3 decades, emphasizing the urgent need for the development of more effective treatment strategies A better understanding of the mechanisms of tumorigenesis has led to novel molecular targeted options for cancer treatment In this regard, we have observed that the persistent activation of the v-akt murine thymoma viral oncogene homolog 1Akt pathway is a frequent event in HNSCC Akt promotes cell proliferation by coordinating mitogenic signaling with energy and nutrient sensing pathways that control protein synthesis through the mammalian target of rapamycin (mTOR) This kinase, in turn, phosphorylates and activates key regulatory circuitries involved in mRNA translation, cell metabolism, and cell cycle control Indeed, the activation of mTOR was found to be a widespread event in HNSCC, as judged by the detection of phospho-S6 (pS6), one of the most downstream targets of mTOR, in more than 80% of human HNSCCs The promising development of mTOR inhibitors, including rapamycin (sirolimus) and its derivatives known as rapalogs, such as CCI-779 (temsilorimus), RAD001 (everolimus), and AP23573 (deterolimus), as antitumor agents prompted us to investigate the effects of rapamycin in HNSCC Indeed rapamycin treatment rapidly reduced the enhanced level of pS6 in vitro and in xenograft models Furthermore, rapamycin displays a potent antitumor effect in vivo, as it Induces apoptosis in HNSCC xenografts, and promotes the regression of chemically induced SCC lesions in skin and oral cancer models and in newly developed oral-specific, genetically defined mouse cancer models In this chapter, we will describe a series of research efforts aimed at addressing dysregulated molecular mechanisms in HNSCC, focusing on the PI3K-Akt-mTOR signaling axis We will also discuss recent and ongoing studies on the molecular targets of mTOR in HNSCC, and emerging experimental information supporting the effectiveness of mTOR inhibitors for the prevention and treatment of HNSCC C1 [Amornphimoltham, Panomwat; Patel, Vyomesh; Molinolo, Alfredo; Gutkind, J. Silvio] Natl Inst Craniofacial & Dent Res, Oral & Pharyngeal Canc Branch, NIH, Bethesda, MD 20892 USA. RP Gutkind, JS (reprint author), Natl Inst Craniofacial & Dent Res, Oral & Pharyngeal Canc Branch, NIH, 30 Convent Dr,Bldg 30,Room 212, Bethesda, MD 20892 USA. NR 80 TC 1 Z9 1 U1 0 U2 6 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013, UNITED STATES BN 978-1-4419-7202-6 PY 2011 BP 407 EP 429 DI 10.1007/978-1-4419-7203-3_19 D2 10.1007/978-1-4419-7203-3 PG 23 WC Oncology SC Oncology GA BSQ66 UT WOS:000285483600019 ER PT S AU Seol, Y Neuman, KC AF Seol, Yeonee Neuman, Keir C. BE Mashanov, GI Batters, C TI Single-Molecule Measurements of Topoisomerase Activity with Magnetic Tweezers SO SINGLE MOLECULE ENZYMOLOGY: METHODS AND PROTOCOLS SE Methods in Molecular Biology LA English DT Article; Book Chapter DE Magnetic tweezers; Single molecule; DNA topology; DNA topoisomerase ID DNA TOPOISOMERASES; TOPOLOGY; FORCE; MICROMANIPULATION; LEVEL AB Magnetic tweezers provide a versatile tool enabling the precise application of force and torque on individual biomolecules. These properties make magnetic tweezers uniquely suited for the study of DNA topology and topoisomerases at the single-molecule level. Single-molecule approaches, which are complementary to ensemble biochemical and structural approaches, have provided remarkable insights into the mechanisms of topoisomerase activity and interactions with DNA. Here, we describe how to make single-molecule measurements of topoisomerase activity with a magnetic tweezers instrument. We provide detailed instructions for preparing and characterizing DNA substrates, flow cells, and supercoilable DNA tethers. We then describe magnetic tweezers measurements of supercoil relaxation by single topoisomerases. C1 [Seol, Yeonee; Neuman, Keir C.] NHLBI, Lab Mol Biophys, NIH, Bethesda, MD 20892 USA. RP Seol, Y (reprint author), NHLBI, Lab Mol Biophys, NIH, Bldg 10, Bethesda, MD 20892 USA. RI Neuman, Keir/F-7400-2011 OI Neuman, Keir/0000-0002-0863-5671 FU Intramural NIH HHS NR 18 TC 10 Z9 10 U1 2 U2 3 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DR, STE 208, TOTOWA, NJ 07512-1165 USA SN 1064-3745 BN 978-1-61779-260-1 J9 METHODS MOL BIOL JI Methods Mol. Biol. PY 2011 VL 778 BP 229 EP 241 DI 10.1007/978-1-61779-261-8_15 D2 10.1007/978-1-61779-261-8 PG 13 WC Biochemical Research Methods; Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA BWO08 UT WOS:000294369000015 PM 21809210 ER PT B AU Alevizos, I Chiorini, JA Nikolov, NP AF Alevizos, Ilias Chiorini, John A. Nikolov, Nikolay P. BE Fox, RI Fox, CM TI Into the Future: Autonomic Neuropathy, MicroRNAs, and Gene Therapy SO SJOGREN'S SYNDROME: PRACTICAL GUIDELINES TO DIAGNOSIS AND THERAPY LA English DT Article; Book Chapter DE Autonomic nervous system; Dysautonomia; microRNA; Gene therapy ID PRIMARY SJOGRENS-SYNDROME; CAENORHABDITIS-ELEGANS; MURINE MODEL; CANCER; EXPRESSION; RNAS; BIOMARKERS; IDENTIFICATION; PROGNOSIS; DIAGNOSIS AB Understanding the pathogenesis of Sjogren's syndrome (SS) has proved to be challenging. Both immune-mediated and non-immune-mediated mechanisms have been implicated, which adds to the complexity of the problem. However, recent developments in science and technology have given researchers new opportunities for exploring this fascinating disease. In this chapter we provide a synopsis of the progress in our understanding of the role of the autonomic nervous system in SS pathogenesis, the role of microRNAs as novel tools in advancing research in this field, and gene therapy as potential therapeutic avenue. C1 [Alevizos, Ilias; Nikolov, Nikolay P.] Natl Inst Dent & Craniofacial Res, Sjogrens Syndrome Clin, Bethesda, MD USA. [Chiorini, John A.] Natl Inst Dent & Craniofacial Res, Dept Mol Physiol, Bethesda, MD USA. [Chiorini, John A.] Natl Inst Dent & Craniofacial Res, Therapeut Branch, Bethesda, MD USA. RP Nikolov, NP (reprint author), Natl Inst Dent & Craniofacial Res, Sjogrens Syndrome Clin, Bethesda, MD USA. EM alvizosi@nidcr.nih.gov; jchiorin@mail.nih.gov; nikolovn@mail.nih.gov NR 36 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013, UNITED STATES BN 978-1-60327-956-7 PY 2011 BP 483 EP 488 DI 10.1007/978-1-60327-957-4_34 D2 10.1007/978-1-60327-957-4 PG 6 WC Rheumatology SC Rheumatology GA BZP36 UT WOS:000302322600034 ER PT J AU Wu, CW Liu, P Wu, Y Chen, C Yang, Y Lin, C AF Wu, C. W. Liu, P. Wu, Y. Chen, C. Yang, Y. Lin, C. TI DESYNCHRONIZATION OF SENSORIMOTOR AND DEFAULT-MODE NETWORKS DURING FIRST SLEEP CYCLE SO SLEEP LA English DT Meeting Abstract CT 25th Anniversary Meeting of the Associated-Professional-Sleep-Societies (APSS) CY JUN 11-15, 2011 CL Minneapolis, MN SP Associated Profess Sleep Soc (APSS) C1 [Wu, C. W.; Yang, Y.] NIDA, Neuroimaging Res Branch, Baltimore, MD USA. [Lin, C.] Natl Yang Ming Univ, Inst Neurosci, Taipei 112, Taiwan. [Chen, C.] Kaohsiung Med Univ, Kaohsiung, Taiwan. [Wu, Y.] Cheng Hsin Gen Hosp, Med Imaging Dept, Taipei, Taiwan. [Wu, Y.] Natl Tsing Hua Univ, Inst Nucl Engn & Sci, Hsinchu, Taiwan. NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER ACAD SLEEP MEDICINE PI WESTCHESTER PA ONE WESTBROOK CORPORATE CTR, STE 920, WESTCHESTER, IL 60154 USA SN 0161-8105 J9 SLEEP JI Sleep PY 2011 VL 34 SU S MA 0103 BP A38 EP A39 PG 2 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 886EG UT WOS:000299834400105 ER PT S AU Duyn, J AF Duyn, Jeff BE VanSomeren, EJW VanDerWerf, YD Roelfsema, PR Mansvelder, HD DaSilva, FHL TI Spontaneous fMRI activity during resting wakefulness and sleep SO SLOW BRAIN OSCILLATIONS OF SLEEP, RESTING STATE AND VIGILANCE SE Progress in Brain Research LA English DT Review CT 26th International Summer School of Brain Research CY JUN 29-JUL 02, 2010 CL Royal Netherlands Acad Arts & Sci (KNAW), Amsterdam, NETHERLANDS SP UCB Pharma, BIAL Fdn, Jonge Academie, Easycap, Elect Geodes Inc (EGI), Grad Sch Neurosci Amsterdam Rotterdam (ONWAR), Leiden Univ Med Ctr (LUMC), MedCaT, Netherlands Inst Neurosci (NIN), Netherlands Soc Sleep-Wake Res (NSWO), Philips Hlth Care, Philips Consumer Lifestyle, Zorg Onderzoek Nederland-Maatschappij Wetenschappen (ZONMW), VU Univ Amsterdam, Univ Amsterdam, VU Univ Med Ctr HO Royal Netherlands Acad Arts & Sci (KNAW) DE sleep; brain function; fmri; spontaneous activity; connectivity; fluctuations ID CEREBRAL-BLOOD-FLOW; INTRINSIC FUNCTIONAL CONNECTIVITY; POSITRON-EMISSION-TOMOGRAPHY; FREQUENCY BOLD FLUCTUATIONS; SPONTANEOUS BRAIN ACTIVITY; HUMAN VISUAL-CORTEX; SLOW OSCILLATIONS; STATE NETWORKS; DEFAULT MODE; ALPHA-RHYTHM AB Functional magnetic resonance imaging (fMRI) studies performed during both waking rest and sleep show that the brain is continually active in distinct patterns that appear to reflect its underlying functional connectivity. In this review, potential sources that contribute to spontaneous fMRI activity will be discussed. C1 NINDS, Sect Adv MRI, LFMI, NIH, Bethesda, MD 20892 USA. RP Duyn, J (reprint author), NINDS, Sect Adv MRI, LFMI, NIH, Bldg 36,Rm 4D04, Bethesda, MD 20892 USA. EM jhd@helix.nih.gov FU Intramural NIH HHS [Z01 NS002990-09] NR 108 TC 7 Z9 7 U1 1 U2 4 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA SARA BURGERHARTSTRAAT 25, PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0079-6123 BN 978-0-44-453838-3 J9 PROG BRAIN RES JI Prog. Brain Res. PY 2011 VL 193 BP 295 EP 305 DI 10.1016/B978-0-444-53839-0.00019-3 PG 11 WC Neurosciences SC Neurosciences & Neurology GA BDA93 UT WOS:000312400500020 PM 21854970 ER PT J AU Strenziok, M Krueger, F Heinecke, A Lenroot, RK Knutson, KM van der Meer, E Grafman, J AF Strenziok, Maren Krueger, Frank Heinecke, Armin Lenroot, Rhoshel K. Knutson, Kristine M. van der Meer, Elke Grafman, Jordan TI Developmental effects of aggressive behavior in male adolescents assessed with structural and functional brain imaging SO SOCIAL COGNITIVE AND AFFECTIVE NEUROSCIENCE LA English DT Article DE ventromedial prefrontal cortex; frontopolar cortex; fMRI; cortical thickness; neurodevelopment; trait anger ID MEDIAL PREFRONTAL CORTEX; POSITRON-EMISSION-TOMOGRAPHY; PERSONALITY-DISORDER; CORTICAL THICKNESS; MOTOR IMAGERY; SOCIAL BRAIN; FMRI; ACTIVATION; ANGER; CHILDREN AB Aggressive behavior is common during adolescence. Although aggression-related functional changes in the ventromedial prefrontal cortex (vmPFC) and frontopolar cortex (FPC) have been reported in adults, the neural correlates of aggressive behavior in adolescents, particularly in the context of structural neurodevelopment, are obscure. We used functional and structural magnetic resonance imaging (MRI) to measure the blood oxygenation level-depended signal and cortical thickness. In a block-designed experiment, 14-17-year old adolescents imagined aggressive and non-aggressive interactions with a peer. We show reduced vmPFC activation associated with imagined aggressive behavior as well as enhanced aggression-related activation and cortical thinning in the FPC with increasing age. Changes in FPC activation were also associated with judgments of the severity of aggressive acts. Reduced vmPFC activation was associated with greater aggression indicating its normal function is to exert inhibitory control over aggressive impulses. Concurrent FPC activation likely reflects foresight of harmful consequences that result from aggressive acts. The correlation of age-dependent activation changes and cortical thinning demonstrates ongoing maturation of the FPC during adolescence towards a refinement of social and cognitive information processing that can potentially facilitate mature social behavior in aggressive contexts. C1 [Grafman, Jordan] NINDS, Cognit Neurosci Sect, NIH, Bethesda, MD 20892 USA. [Strenziok, Maren; van der Meer, Elke] Humboldt Univ, Dept Cognit Psychol, Inst Psychol, D-12489 Berlin, Germany. [Heinecke, Armin] Brain Innovat, NL-6201 BC Maastricht, Netherlands. [Lenroot, Rhoshel K.] NIMH, Child Psychiat Branch, Bethesda, MD 20892 USA. RP Grafman, J (reprint author), NINDS, Cognit Neurosci Sect, NIH, 10 Ctr Dr,Bldg 10,Room 7D43, Bethesda, MD 20892 USA. EM grafmanj@ninds.nih.gov OI Grafman, Jordan H./0000-0001-8645-4457; Knutson, Kristine/0000-0003-4626-4514 FU National Institutes of Health, National Institute of Neurological Disorders and Stroke FX This work was funded by the intramural research program of the National Institutes of Health, National Institute of Neurological Disorders and Stroke. We thank Dr Eric Wassermann, Dr Dimitrios Kapogiannis and Dr Edward Huey for performing the neurological examinations in our participants. NR 68 TC 9 Z9 10 U1 4 U2 21 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 1749-5016 J9 SOC COGN AFFECT NEUR JI Soc. Cogn. Affect. Neurosci. PD JAN PY 2011 VL 6 IS 1 BP 2 EP 11 DI 10.1093/scan/nsp036 PG 10 WC Neurosciences; Psychology; Psychology, Experimental SC Neurosciences & Neurology; Psychology GA 752XT UT WOS:000289729500002 PM 19770220 ER PT S AU Mabry, PL Hammond, R Huang, TTK Ip, EHS AF Mabry, Patricia L. Hammond, Ross Huang, Terry T-K Ip, Edward Hak-Sing BE Salerno, J Yang, SJ Nau, D Chai, SK TI Computational and Statistical Models: A Comparison for Policy Modeling of Childhood Obesity SO SOCIAL COMPUTING, BEHAVIORAL-CULTURAL MODELING AND PREDICTION SE Lecture Notes in Computer Science LA English DT Proceedings Paper CT 4th International Conference on Social Computing, Behavioral-Cultural Modeling and Prediction CY MAR 29-31, 2011 CL Coll Pk, MD C1 [Mabry, Patricia L.] NIH, Off Director, Off Behav & Social Sci Res, Bethesda, MD 20892 USA. [Hammond, Ross] Ctr Social Dynam & Policy, Brookings Inst, Econ Studies, Washington, DC 20036 USA. [Huang, Terry T-K] Univ Nebraska, Med Ctr, Coll Publ Hlth, Dept Hlth Promot & Social Behavioral Hlth, Lincoln, NE 68583 USA. [Ip, Edward Hak-Sing] Wake Forest Univ Hlth Sci, Res & Fac Dev, Div Publ Hlth Sci, Winston Salem, NC 27109 USA. RP Mabry, PL (reprint author), NIH, Off Director, Off Behav & Social Sci Res, Bethesda, MD 20892 USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU SPRINGER-VERLAG BERLIN PI BERLIN PA HEIDELBERGER PLATZ 3, D-14197 BERLIN, GERMANY SN 0302-9743 BN 978-3-642-19655-3 J9 LECT NOTES COMPUT SC PY 2011 VL 6589 BP 87 EP + PG 2 WC Computer Science, Information Systems; Computer Science, Software Engineering; Computer Science, Theory & Methods SC Computer Science GA BXT86 UT WOS:000297039300014 ER PT J AU Laugeson, EA Frankel, F AF Laugeson, Elizabeth A. Frankel, Fred BA Laugeson, EA Frankel, F BF Laugeson, EA Frankel, F TI Social Skills for Teenagers With Developmental and Autism Spectrum Disorders THE PEERS TREATMENT MANUAL Introduction SO SOCIAL SKILLS FOR TEENAGERS WITH DEVELOPMENTAL AND AUTISM SPECTRUM DISORDERS LA English DT Article; Book Chapter C1 [Frankel, Fred] NIMH, Bethesda, MD USA. [Frankel, Fred] Ctr Dis Control & Prevent CDC, Atlanta, GA USA. [Frankel, Fred] NIH, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 4 PU ROUTLEDGE PI LONDON PA 11 NEW FETTER LANE, LONDON EC4P 4EE, ENGLAND BN 978-0-415-87203-4 PY 2011 BP 3 EP + PG 15 WC Education, Special; Psychology, Developmental; Pediatrics; Psychiatry; Psychology; Psychology, Social SC Education & Educational Research; Psychology; Pediatrics; Psychiatry GA BUZ15 UT WOS:000290759100001 ER PT J AU Laugeson, EA Frankel, F AF Laugeson, Elizabeth A. Frankel, Fred BA Laugeson, EA Frankel, F BF Laugeson, EA Frankel, F TI Preparing for Treatment SO SOCIAL SKILLS FOR TEENAGERS WITH DEVELOPMENTAL AND AUTISM SPECTRUM DISORDERS LA English DT Article; Book Chapter C1 [Frankel, Fred] NIMH, Bethesda, MD USA. [Frankel, Fred] Ctr Dis Control & Prevent CDC, Atlanta, GA USA. [Frankel, Fred] NIH, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ROUTLEDGE PI LONDON PA 11 NEW FETTER LANE, LONDON EC4P 4EE, ENGLAND BN 978-0-415-87203-4 PY 2011 BP 17 EP 34 PG 18 WC Education, Special; Psychology, Developmental; Pediatrics; Psychiatry; Psychology; Psychology, Social SC Education & Educational Research; Psychology; Pediatrics; Psychiatry GA BUZ15 UT WOS:000290759100002 ER PT J AU Laugeson, EA Frankel, F AF Laugeson, Elizabeth A. Frankel, Fred BA Laugeson, EA Frankel, F BF Laugeson, EA Frankel, F TI Session 1 Introduction and Conversational Skills I-Trading Information SO SOCIAL SKILLS FOR TEENAGERS WITH DEVELOPMENTAL AND AUTISM SPECTRUM DISORDERS LA English DT Article; Book Chapter C1 [Frankel, Fred] NIMH, Bethesda, MD USA. [Frankel, Fred] Ctr Dis Control & Prevent CDC, Atlanta, GA USA. [Frankel, Fred] NIH, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ROUTLEDGE PI LONDON PA 11 NEW FETTER LANE, LONDON EC4P 4EE, ENGLAND BN 978-0-415-87203-4 PY 2011 BP 37 EP 65 PG 29 WC Education, Special; Psychology, Developmental; Pediatrics; Psychiatry; Psychology; Psychology, Social SC Education & Educational Research; Psychology; Pediatrics; Psychiatry GA BUZ15 UT WOS:000290759100003 ER PT J AU Laugeson, EA Frankel, F AF Laugeson, Elizabeth A. Frankel, Fred BA Laugeson, EA Frankel, F BF Laugeson, EA Frankel, F TI Session 2 Conversational Skills II-Two-Way Conversations SO SOCIAL SKILLS FOR TEENAGERS WITH DEVELOPMENTAL AND AUTISM SPECTRUM DISORDERS LA English DT Article; Book Chapter C1 [Frankel, Fred] NIMH, Bethesda, MD USA. [Frankel, Fred] Ctr Dis Control & Prevent CDC, Atlanta, GA USA. [Frankel, Fred] NIH, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ROUTLEDGE PI LONDON PA 11 NEW FETTER LANE, LONDON EC4P 4EE, ENGLAND BN 978-0-415-87203-4 PY 2011 BP 67 EP 93 PG 27 WC Education, Special; Psychology, Developmental; Pediatrics; Psychiatry; Psychology; Psychology, Social SC Education & Educational Research; Psychology; Pediatrics; Psychiatry GA BUZ15 UT WOS:000290759100004 ER PT J AU Laugeson, EA Frankel, F AF Laugeson, Elizabeth A. Frankel, Fred BA Laugeson, EA Frankel, F BF Laugeson, EA Frankel, F TI Session 3 Conversational Skills III-Electronic Communication SO SOCIAL SKILLS FOR TEENAGERS WITH DEVELOPMENTAL AND AUTISM SPECTRUM DISORDERS LA English DT Article; Book Chapter C1 [Frankel, Fred] NIMH, Bethesda, MD USA. [Frankel, Fred] Ctr Dis Control & Prevent CDC, Atlanta, GA USA. [Frankel, Fred] NIH, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ROUTLEDGE PI LONDON PA 11 NEW FETTER LANE, LONDON EC4P 4EE, ENGLAND BN 978-0-415-87203-4 PY 2011 BP 95 EP 123 PG 29 WC Education, Special; Psychology, Developmental; Pediatrics; Psychiatry; Psychology; Psychology, Social SC Education & Educational Research; Psychology; Pediatrics; Psychiatry GA BUZ15 UT WOS:000290759100005 ER PT J AU Laugeson, EA Frankel, F AF Laugeson, Elizabeth A. Frankel, Fred BA Laugeson, EA Frankel, F BF Laugeson, EA Frankel, F TI Session 4 Choosing Appropriate Friends SO SOCIAL SKILLS FOR TEENAGERS WITH DEVELOPMENTAL AND AUTISM SPECTRUM DISORDERS LA English DT Article; Book Chapter C1 [Frankel, Fred] NIMH, Bethesda, MD USA. [Frankel, Fred] Ctr Dis Control & Prevent CDC, Atlanta, GA USA. [Frankel, Fred] NIH, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ROUTLEDGE PI LONDON PA 11 NEW FETTER LANE, LONDON EC4P 4EE, ENGLAND BN 978-0-415-87203-4 PY 2011 BP 125 EP 145 PG 21 WC Education, Special; Psychology, Developmental; Pediatrics; Psychiatry; Psychology; Psychology, Social SC Education & Educational Research; Psychology; Pediatrics; Psychiatry GA BUZ15 UT WOS:000290759100006 ER PT J AU Laugeson, EA Frankel, F AF Laugeson, Elizabeth A. Frankel, Fred BA Laugeson, EA Frankel, F BF Laugeson, EA Frankel, F TI Session 5 Appropriate Use of Humor SO SOCIAL SKILLS FOR TEENAGERS WITH DEVELOPMENTAL AND AUTISM SPECTRUM DISORDERS LA English DT Article; Book Chapter C1 [Frankel, Fred] NIMH, Bethesda, MD USA. [Frankel, Fred] Ctr Dis Control & Prevent CDC, Atlanta, GA USA. [Frankel, Fred] NIH, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ROUTLEDGE PI LONDON PA 11 NEW FETTER LANE, LONDON EC4P 4EE, ENGLAND BN 978-0-415-87203-4 PY 2011 BP 147 EP 170 PG 24 WC Education, Special; Psychology, Developmental; Pediatrics; Psychiatry; Psychology; Psychology, Social SC Education & Educational Research; Psychology; Pediatrics; Psychiatry GA BUZ15 UT WOS:000290759100007 ER PT J AU Laugeson, EA Frankel, F AF Laugeson, Elizabeth A. Frankel, Fred BA Laugeson, EA Frankel, F BF Laugeson, EA Frankel, F TI Session 6 Peer Entry I-Entering a Conversation SO SOCIAL SKILLS FOR TEENAGERS WITH DEVELOPMENTAL AND AUTISM SPECTRUM DISORDERS LA English DT Article; Book Chapter C1 [Frankel, Fred] NIMH, Bethesda, MD USA. [Frankel, Fred] Ctr Dis Control & Prevent CDC, Atlanta, GA USA. [Frankel, Fred] NIH, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ROUTLEDGE PI LONDON PA 11 NEW FETTER LANE, LONDON EC4P 4EE, ENGLAND BN 978-0-415-87203-4 PY 2011 BP 171 EP 197 PG 27 WC Education, Special; Psychology, Developmental; Pediatrics; Psychiatry; Psychology; Psychology, Social SC Education & Educational Research; Psychology; Pediatrics; Psychiatry GA BUZ15 UT WOS:000290759100008 ER PT J AU Laugeson, EA Frankel, F AF Laugeson, Elizabeth A. Frankel, Fred BA Laugeson, EA Frankel, F BF Laugeson, EA Frankel, F TI Session 7 Peer Entry II-Exiting a Conversation SO SOCIAL SKILLS FOR TEENAGERS WITH DEVELOPMENTAL AND AUTISM SPECTRUM DISORDERS LA English DT Article; Book Chapter C1 [Frankel, Fred] NIMH, Bethesda, MD USA. [Frankel, Fred] Ctr Dis Control & Prevent CDC, Atlanta, GA USA. [Frankel, Fred] NIH, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ROUTLEDGE PI LONDON PA 11 NEW FETTER LANE, LONDON EC4P 4EE, ENGLAND BN 978-0-415-87203-4 PY 2011 BP 199 EP 222 PG 24 WC Education, Special; Psychology, Developmental; Pediatrics; Psychiatry; Psychology; Psychology, Social SC Education & Educational Research; Psychology; Pediatrics; Psychiatry GA BUZ15 UT WOS:000290759100009 ER PT J AU Laugeson, EA Frankel, F AF Laugeson, Elizabeth A. Frankel, Fred BA Laugeson, EA Frankel, F BF Laugeson, EA Frankel, F TI Session 8 Get-Togethers SO SOCIAL SKILLS FOR TEENAGERS WITH DEVELOPMENTAL AND AUTISM SPECTRUM DISORDERS LA English DT Article; Book Chapter C1 [Frankel, Fred] NIMH, Bethesda, MD USA. [Frankel, Fred] Ctr Dis Control & Prevent CDC, Atlanta, GA USA. [Frankel, Fred] NIH, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ROUTLEDGE PI LONDON PA 11 NEW FETTER LANE, LONDON EC4P 4EE, ENGLAND BN 978-0-415-87203-4 PY 2011 BP 223 EP 250 PG 28 WC Education, Special; Psychology, Developmental; Pediatrics; Psychiatry; Psychology; Psychology, Social SC Education & Educational Research; Psychology; Pediatrics; Psychiatry GA BUZ15 UT WOS:000290759100010 ER PT J AU Laugeson, EA Frankel, F AF Laugeson, Elizabeth A. Frankel, Fred BA Laugeson, EA Frankel, F BF Laugeson, EA Frankel, F TI Session 9 Good Sportsmanship SO SOCIAL SKILLS FOR TEENAGERS WITH DEVELOPMENTAL AND AUTISM SPECTRUM DISORDERS LA English DT Article; Book Chapter C1 [Frankel, Fred] NIMH, Bethesda, MD USA. [Frankel, Fred] Ctr Dis Control & Prevent CDC, Atlanta, GA USA. [Frankel, Fred] NIH, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU ROUTLEDGE PI LONDON PA 11 NEW FETTER LANE, LONDON EC4P 4EE, ENGLAND BN 978-0-415-87203-4 PY 2011 BP 251 EP 266 PG 16 WC Education, Special; Psychology, Developmental; Pediatrics; Psychiatry; Psychology; Psychology, Social SC Education & Educational Research; Psychology; Pediatrics; Psychiatry GA BUZ15 UT WOS:000290759100011 ER PT J AU Laugeson, EA Frankel, F AF Laugeson, Elizabeth A. Frankel, Fred BA Laugeson, EA Frankel, F BF Laugeson, EA Frankel, F TI Session 10 Rejection I-Teasing and Embarrassing Feedback SO SOCIAL SKILLS FOR TEENAGERS WITH DEVELOPMENTAL AND AUTISM SPECTRUM DISORDERS LA English DT Article; Book Chapter C1 [Frankel, Fred] NIMH, Bethesda, MD USA. [Frankel, Fred] Ctr Dis Control & Prevent CDC, Atlanta, GA USA. [Frankel, Fred] NIH, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ROUTLEDGE PI LONDON PA 11 NEW FETTER LANE, LONDON EC4P 4EE, ENGLAND BN 978-0-415-87203-4 PY 2011 BP 267 EP 291 PG 25 WC Education, Special; Psychology, Developmental; Pediatrics; Psychiatry; Psychology; Psychology, Social SC Education & Educational Research; Psychology; Pediatrics; Psychiatry GA BUZ15 UT WOS:000290759100012 ER PT J AU Laugeson, EA Frankel, F AF Laugeson, Elizabeth A. Frankel, Fred BA Laugeson, EA Frankel, F BF Laugeson, EA Frankel, F TI Session 11 Rejection II-Bullying and Bad Reputations SO SOCIAL SKILLS FOR TEENAGERS WITH DEVELOPMENTAL AND AUTISM SPECTRUM DISORDERS LA English DT Article; Book Chapter C1 [Frankel, Fred] NIMH, Bethesda, MD USA. [Frankel, Fred] Ctr Dis Control & Prevent CDC, Atlanta, GA USA. [Frankel, Fred] NIH, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ROUTLEDGE PI LONDON PA 11 NEW FETTER LANE, LONDON EC4P 4EE, ENGLAND BN 978-0-415-87203-4 PY 2011 BP 293 EP 312 PG 20 WC Education, Special; Psychology, Developmental; Pediatrics; Psychiatry; Psychology; Psychology, Social SC Education & Educational Research; Psychology; Pediatrics; Psychiatry GA BUZ15 UT WOS:000290759100013 ER PT J AU Laugeson, EA Frankel, F AF Laugeson, Elizabeth A. Frankel, Fred BA Laugeson, EA Frankel, F BF Laugeson, EA Frankel, F TI Session 12 Handling Disagreements SO SOCIAL SKILLS FOR TEENAGERS WITH DEVELOPMENTAL AND AUTISM SPECTRUM DISORDERS LA English DT Article; Book Chapter C1 [Frankel, Fred] NIMH, Bethesda, MD USA. [Frankel, Fred] Ctr Dis Control & Prevent CDC, Atlanta, GA USA. [Frankel, Fred] NIH, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ROUTLEDGE PI LONDON PA 11 NEW FETTER LANE, LONDON EC4P 4EE, ENGLAND BN 978-0-415-87203-4 PY 2011 BP 313 EP 335 PG 23 WC Education, Special; Psychology, Developmental; Pediatrics; Psychiatry; Psychology; Psychology, Social SC Education & Educational Research; Psychology; Pediatrics; Psychiatry GA BUZ15 UT WOS:000290759100014 ER PT J AU Laugeson, EA Frankel, F AF Laugeson, Elizabeth A. Frankel, Fred BA Laugeson, EA Frankel, F BF Laugeson, EA Frankel, F TI Session 13 Rumors and Gossip SO SOCIAL SKILLS FOR TEENAGERS WITH DEVELOPMENTAL AND AUTISM SPECTRUM DISORDERS LA English DT Article; Book Chapter C1 [Frankel, Fred] NIMH, Bethesda, MD USA. [Frankel, Fred] Ctr Dis Control & Prevent CDC, Atlanta, GA USA. [Frankel, Fred] NIH, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ROUTLEDGE PI LONDON PA 11 NEW FETTER LANE, LONDON EC4P 4EE, ENGLAND BN 978-0-415-87203-4 PY 2011 BP 337 EP 358 PG 22 WC Education, Special; Psychology, Developmental; Pediatrics; Psychiatry; Psychology; Psychology, Social SC Education & Educational Research; Psychology; Pediatrics; Psychiatry GA BUZ15 UT WOS:000290759100015 ER PT J AU Laugeson, EA Frankel, F AF Laugeson, Elizabeth A. Frankel, Fred BA Laugeson, EA Frankel, F BF Laugeson, EA Frankel, F TI Session 14 Graduation and Termination SO SOCIAL SKILLS FOR TEENAGERS WITH DEVELOPMENTAL AND AUTISM SPECTRUM DISORDERS LA English DT Article; Book Chapter C1 [Frankel, Fred] NIMH, Bethesda, MD USA. [Frankel, Fred] Ctr Dis Control & Prevent CDC, Atlanta, GA USA. [Frankel, Fred] NIH, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ROUTLEDGE PI LONDON PA 11 NEW FETTER LANE, LONDON EC4P 4EE, ENGLAND BN 978-0-415-87203-4 PY 2011 BP 359 EP 372 PG 14 WC Education, Special; Psychology, Developmental; Pediatrics; Psychiatry; Psychology; Psychology, Social SC Education & Educational Research; Psychology; Pediatrics; Psychiatry GA BUZ15 UT WOS:000290759100016 ER PT J AU Laugeson, EA Frankel, F AF Laugeson, Elizabeth A. Frankel, Fred BA Laugeson, EA Frankel, F BF Laugeson, EA Frankel, F TI Case Examples SO SOCIAL SKILLS FOR TEENAGERS WITH DEVELOPMENTAL AND AUTISM SPECTRUM DISORDERS LA English DT Article; Book Chapter C1 [Frankel, Fred] NIMH, Bethesda, MD USA. [Frankel, Fred] Ctr Dis Control & Prevent CDC, Atlanta, GA USA. [Frankel, Fred] NIH, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ROUTLEDGE PI LONDON PA 11 NEW FETTER LANE, LONDON EC4P 4EE, ENGLAND BN 978-0-415-87203-4 PY 2011 BP 373 EP 377 PG 5 WC Education, Special; Psychology, Developmental; Pediatrics; Psychiatry; Psychology; Psychology, Social SC Education & Educational Research; Psychology; Pediatrics; Psychiatry GA BUZ15 UT WOS:000290759100017 ER PT J AU Arce, FT Jang, HB Ramachandran, S Landon, PB Nussinov, R Lal, R AF Arce, Fernando Teran Jang, Hyunbum Ramachandran, Srinivasan Landon, Preston B. Nussinov, Ruth Lal, Ratnesh TI Polymorphism of amyloid beta peptide in different environments: implications for membrane insertion and pore formation SO SOFT MATTER LA English DT Article ID ATOMIC-FORCE MICROSCOPY; ION CHANNELS; ALZHEIMERS-DISEASE; MOLECULAR-DYNAMICS; CARBON INTERACTION; 3D STRUCTURE; PROTEIN; FIBRILS; OLIGOMERS; ENERGY AB Amyloid-beta (A beta) peptides are thought to be involved in neurodegenerative diseases such as Alzheimer's disease and Down's syndrome. They form a large number of polymorphic structures, including heterogeneous ionic pores in membranes as well as different types of fibrillar and globular structures on surfaces and in solution. Understanding the origin of these structures and the factors that influence their occurrence is of great biomedical interest because of the possible relationship between structure and pathogenicity. Here, we use atomic force microscopy (AFM) and molecular dynamics (MD) simulations to demonstrate that at room temperature a truncated A beta peptide which is generated in vivo and shown to be toxic in vitro forms fibrillar structures on hydrophobic graphite surfaces, but not on hydrophilic mica or lipid bilayers. Our results suggest that the toxic pores and fibrillar polymorphic organizations can be explained in terms of the U-shaped beta-strand-turn-beta-strand structural motif observed for full length A beta and other amyloids, as well as the physicochemical properties at the interfaces. The interactions of the hydrophobic, truncated A beta with its environment illustrate that the universal amyloid motif can provide a link between the pore and fibrillar structures and indicate that surfaces with different physicochemical properties can shift the polymorphic landscape toward other conformational states. C1 [Jang, Hyunbum; Nussinov, Ruth] SAIC Frederick Inc, Ctr Canc Res, Nanobiol Program, NCI Frederick, Frederick, MD 21702 USA. [Arce, Fernando Teran; Ramachandran, Srinivasan; Landon, Preston B.; Lal, Ratnesh] Univ Calif San Diego, Dept Bioengn, La Jolla, CA 92093 USA. [Arce, Fernando Teran; Ramachandran, Srinivasan; Landon, Preston B.; Lal, Ratnesh] Univ Calif San Diego, Dept Mech & Aerosp Engn, La Jolla, CA 92093 USA. [Nussinov, Ruth] Tel Aviv Univ, Sackler Inst Mol Med, Dept Human Genet & Mol Med, Sackler Sch Med, IL-69978 Tel Aviv, Israel. RP Nussinov, R (reprint author), SAIC Frederick Inc, Ctr Canc Res, Nanobiol Program, NCI Frederick, Frederick, MD 21702 USA. EM ruthnu@helix.nih.gov; rlal@ucsd.edu FU National Institutes of Health (National Institute on Aging) [AG028709]; National Cancer Institute, National Institutes of Health [HHSN261200800001E]; NIH, National Cancer Institute, Center for Cancer Research FX This research was supported by the National Institutes of Health (National Institute on Aging AG028709 to RL). This project has been funded in whole or in part with Federal funds from the National Cancer Institute, National Institutes of Health, under contract number HHSN261200800001E. This research was supported (in part) by the Intramural Research Program of the NIH, National Cancer Institute, Center for Cancer Research. All simulations had been performed using the high-performance computational facilities of the Biowulf PC/Linux cluster at the National Institutes of Health, Bethesda, MD (http://biowulf.nih.gov). NR 52 TC 33 Z9 33 U1 2 U2 24 PU ROYAL SOC CHEMISTRY PI CAMBRIDGE PA THOMAS GRAHAM HOUSE, SCIENCE PARK, MILTON RD, CAMBRIDGE CB4 0WF, CAMBS, ENGLAND SN 1744-683X EI 1744-6848 J9 SOFT MATTER JI Soft Matter PY 2011 VL 7 IS 11 BP 5267 EP 5273 DI 10.1039/c1sm05162h PG 7 WC Chemistry, Physical; Materials Science, Multidisciplinary; Physics, Multidisciplinary; Polymer Science SC Chemistry; Materials Science; Physics; Polymer Science GA 768LX UT WOS:000290937300026 PM 21918653 ER PT J AU Biering-Sorensen, F Charlifue, S DeVivo, MJ Grinnon, ST Kleitman, N Lu, Y Odenkirchen, J AF Biering-Sorensen, F. Charlifue, S. DeVivo, M. J. Grinnon, S. T. Kleitman, N. Lu, Y. Odenkirchen, J. TI Incorporation of the International Spinal Cord Injury Data Set elements into the National Institute of Neurological Disorders and Stroke Common Data Elements SO SPINAL CORD LA English DT Article DE spinal cord injury; International; Data Set; variable names; database specifications; common data element ID BASIC DATA SET AB Objectives: To develop consistent variable names and a common database structure for the data elements in the International Spinal Cord Injury (SCI) Data Sets. Setting: National Institute of Neurological Disorders and Stroke (NINDS) Common Data Elements (CDE) Project and The Executive Committee of the International SCI Standards and Data Sets committees (ECSCI). Methods: The NINDS CDE team creates a variable name for each defined data element in the various International SCI Data Sets. Members of the ECSCI review these in an iterative process to make the variable names logical and consistent across the data sets. Following this process, the working group for the particular data set reviews the variable names, and further revisions and adjustments may be made. In addition, a database structure for each data set is developed allowing data to be stored in a uniform way in databases to promote sharing data from different studies. Results: The International SCI Data Sets variable names and database specifications will be available through the web sites of the International Spinal Cord Society (http://www.iscos.org.uk), the American Spinal Injury Association (http://www.asia-spinalinjury.org) and the NINDS CDE project web site (http://www.CommonDataElements.ninds.nih.gov). Conclusion: This process will continue as additional International SCI Data Sets fulfill the requirements of the development and approval process and are ready for implementation. Spinal Cord (2011) 49, 60-64; doi: 10.1038/sc.2010.90; published online 24 August 2010 C1 [Biering-Sorensen, F.] Rigshosp, Ctr Neurosci, Clin Spinal Cord Injuries, DK-2100 Copenhagen, Denmark. [Biering-Sorensen, F.] Univ Copenhagen, Copenhagen, Denmark. [Charlifue, S.] Craig Hosp, Englewood, CO USA. [DeVivo, M. J.] Univ Alabama, Dept Phys Med & Rehabil, Birmingham, AL USA. [Grinnon, S. T.; Lu, Y.] KAI Res Inc, Rockville, MD USA. [Kleitman, N.; Odenkirchen, J.] NINDS, NIH, Bethesda, MD 20892 USA. RP Biering-Sorensen, F (reprint author), Rigshosp, Ctr Neurosci, Clin Spinal Cord Injuries, TH2091,Blegdamsvej 9, DK-2100 Copenhagen, Denmark. EM finbs@rh.regionh.dk OI Kleitman, Naomi/0000-0003-1089-0257 FU Intramural NIH HHS [Z99 NS999999] NR 12 TC 18 Z9 20 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1362-4393 J9 SPINAL CORD JI Spinal Cord PD JAN PY 2011 VL 49 IS 1 BP 60 EP 64 DI 10.1038/sc.2010.90 PG 5 WC Clinical Neurology; Rehabilitation SC Neurosciences & Neurology; Rehabilitation GA 703QU UT WOS:000285996800010 PM 20733589 ER PT J AU Huestis, MA Mazzoni, I Rabin, O AF Huestis, Marilyn A. Mazzoni, Irene Rabin, Olivier TI Cannabis in Sport Anti-Doping Perspective SO SPORTS MEDICINE LA English DT Review ID PASSIVE INHALATION; DELTA-9-TETRAHYDROCANNABINOL THC; ENDOCANNABINOID SYSTEM; URINARY-EXCRETION; MARIJUANA USE; BRAIN REWARD; CIGARETTE-SMOKE; GC-MS; PERFORMANCE; DRUGS AB Since 2004, when the World Anti-Doping Agency assumed the responsibility for establishing and maintaining the list of prohibited substances and methods in sport (i.e. the Prohibited List), cannabinoids have been prohibited in all sports during competition. The basis for this prohibition can be found in the World Anti-Doping Code, which defines the three criteria used to consider banning a substance. In this context, we discuss the potential of cannabis to enhance sports performance, the risk it poses to the athlete's health and its violation of the spirit of sport. Although these compounds are prohibited in-competition only, we explain why the pharmacokinetics of their main psychoactive compound, Delta(9)-tetrahydrocannabinol, may complicate the results management of adverse analytical findings. Passive inhalation does not appear to be a plausible explanation for a positive test. Although the prohibition of cannabinoids in sports is one of the most controversial issues in anti-doping, in this review we stress the reasons behind this prohibition, with strong emphasis on the evolving knowledge of cannabinoid pharmacology. C1 [Huestis, Marilyn A.] NIDA, Intramural Res Program, NIH, Baltimore, MD 21224 USA. [Mazzoni, Irene; Rabin, Olivier] World Antidoping Agcy, Montreal, PQ, Canada. RP Huestis, MA (reprint author), NIDA, Intramural Res Program, NIH, 251 Bayview Blvd,Suite 05-721, Baltimore, MD 21224 USA. EM mhuestis@intra.nida.nih.gov FU Intramural NIH HHS [Z01 DA000413-11, ZIA DA000413-12] NR 135 TC 14 Z9 14 U1 2 U2 17 PU ADIS INT LTD PI AUCKLAND PA 41 CENTORIAN DR, PRIVATE BAG 65901, MAIRANGI BAY, AUCKLAND 1311, NEW ZEALAND SN 0112-1642 J9 SPORTS MED JI Sports Med. PY 2011 VL 41 IS 11 BP 949 EP 966 PG 18 WC Sport Sciences SC Sport Sciences GA 845KU UT WOS:000296822400004 PM 21985215 ER PT J AU Klimke, W O'Donovan, C White, O Brister, JR Clark, K Fedorov, B Mizrachi, I Pruitt, KD Tatusova, T AF Klimke, William O'Donovan, Claire White, Owen Brister, J. Rodney Clark, Karen Fedorov, Boris Mizrachi, Ilene Pruitt, Kim D. Tatusova, Tatiana TI Solving the Problem: Genome Annotation Standards before the data deluge SO STANDARDS IN GENOMIC SCIENCES LA English DT Article ID ESCHERICHIA-COLI K-12; MINIMUM INFORMATION; MICROBIAL GENOMES; GENETIC ELEMENTS; RNA GENES; SEQUENCE; RESOURCE; UPDATE; BACTERIA; ARCHIVE AB The promise of genome sequencing was that the vast undiscovered country would be mapped out by comparison of the multitude of sequences available and would aid researchers in deciphering the role of each gene in every organism. Researchers recognize that there is a need for high quality data. However, different annotation procedures, numerous databases, and a diminishing percentage of experimentally determined gene functions have resulted in a spectrum of annotation quality. NCBI in collaboration with sequencing centers, archival databases, and researchers, has developed the first international annotation standards, a fundamental step in ensuring that high quality complete prokaryotic genomes are available as gold standard references. Highlights include the development of annotation assessment tools, community acceptance of protein naming standards, comparison of annotation resources to provide consistent annotation, and improved tracking of the evidence used to generate a particular annotation. The development of a set of minimal standards, including the requirement for annotated complete prokaryotic genomes to contain a full set of ribosomal RNAs, transfer RNAs, and proteins encoding core conserved functions, is an historic milestone. The use of these standards in existing genomes and future submissions will increase the quality of databases, enabling researchers to make accurate biological discoveries. C1 [Klimke, William; Brister, J. Rodney; Clark, Karen; Fedorov, Boris; Mizrachi, Ilene; Pruitt, Kim D.; Tatusova, Tatiana] NIH, Natl Ctr Biotechnol Informat, Natl Lib Med, Bethesda, MD 20894 USA. [O'Donovan, Claire] European Bioinformat Inst, UniProt, EMBL Outstn, Cambridge CB10 1SD, England. [White, Owen] Univ Maryland, Sch Med, Inst Genome Sci, Baltimore, MD 21201 USA. RP Klimke, W (reprint author), NIH, Natl Ctr Biotechnol Informat, Natl Lib Med, Bldg 45, Bethesda, MD 20894 USA. OI O'Donovan, Claire/0000-0001-8051-7429 FU National Institutes of Health; National Library of Medicine FX The authors would like to thank the J. Craig Venter Institute for hosting the workshop and especially Tanja Davidsen and Ramana Madupu for help in the organization before, during, and after the workshop. Funding for the open access charge was provided by the Intramural Research Program of the National Institutes of Health; National Library of Medicine. NR 81 TC 21 Z9 22 U1 1 U2 8 PU GENOMIC STAND CONSORT PI EAST LANSING PA MICHIGAN STATE UNIV, GEEO GARRITY, DEPT MICROBIOL, 6162 BIOMED & PHYS SCI BLDG, EAST LANSING, MI 48824 USA SN 1944-3277 J9 STAND GENOMIC SCI JI Stand. Genomic Sci. PY 2011 VL 5 IS 1 BP 168 EP 193 DI 10.4056/sigs.2084864 PG 26 WC Genetics & Heredity; Microbiology SC Genetics & Heredity; Microbiology GA 874GU UT WOS:000298944200016 PM 22180819 ER PT J AU Buckle, AM Bate, MA Androulakis, S Cinquanta, M Basquin, J Bonneau, F Chatterjee, DK Cittaro, D Graslund, S Gruszka, A Page, R Suppmann, S Wheeler, JX Agostini, D Taussig, M Taylor, CF Bottomley, SP Villaverde, A de Marco, A AF Buckle, Ashley M. Bate, Mark A. Androulakis, Steve Cinquanta, Mario Basquin, Jerome Bonneau, Fabien Chatterjee, Deb K. Cittaro, Davide Graslund, Susanne Gruszka, Alicja Page, Rebecca Suppmann, Sabine Wheeler, Jun X. Agostini, Deborah Taussig, Mike Taylor, Chris F. Bottomley, Stephen P. Villaverde, Antonio de Marco, Ario TI Recombinant protein quality evaluation: proposal for a minimal information standard SO STANDARDS IN GENOMIC SCIENCES LA English DT Editorial Material ID GUIDELINES C1 [de Marco, Ario] UNG, Dept Environm Sci, Rozna Dolina, Nova Gorica, Slovenia. [Buckle, Ashley M.; Bate, Mark A.; Bottomley, Stephen P.] Monash Univ, Dept Biochem & Mol Biol, Sch Biomed Sci, Fac Med Nursing & Hlth Sci, Clayton, Vic 3800, Australia. [Androulakis, Steve] Monash Univ, Monash ERes Ctr, Clayton, Vic, Australia. [Cinquanta, Mario; Cittaro, Davide; Agostini, Deborah] Cogentech, Prot Chem Unit, Milan, Italy. [Basquin, Jerome; Bonneau, Fabien] Max Planck Inst Biochem, Dept Struct Cell Biol, D-82152 Martinsried, Germany. [Chatterjee, Deb K.] NCI, Prot Express Lab, SAIC Frederick Inc, Frederick, MD 21701 USA. [Graslund, Susanne] Karolinska Inst, Struct Genom Consortium, Dept Med Biophys & Biochem, Stockholm, Sweden. [Gruszka, Alicja] IEO, Milan, Italy. [Page, Rebecca] Brown Univ, Dept Mol Biol Cell Biol & Biochem, Providence, RI 02912 USA. [Suppmann, Sabine] Max Planck Inst Biochem, Microchem Core Facil, D-82152 Martinsried, Germany. [Taussig, Mike] Babraham Biosci Technol, Prot Technol Grp, Cambridge, England. [Taylor, Chris F.] European Bioinformat Inst, Hinxton, Cambs, England. [Villaverde, Antonio] Univ Autonoma Barcelona, Inst Biotechnol & Biomed, E-08193 Barcelona, Spain. [Villaverde, Antonio] Univ Autonoma Barcelona, Dept Genet & Microbiol, E-08193 Barcelona, Spain. [Villaverde, Antonio] CIBER Bioingn Biomat & Nanomed CIBER BBN, Barcelona, Spain. RP de Marco, A (reprint author), UNG, Dept Environm Sci, Rozna Dolina, Nova Gorica, Slovenia. EM ario.demarco@ung.si RI Buckle, Ashley/P-8366-2016; OI Buckle, Ashley/0000-0003-2943-9044; Gruszka, Alicja M/0000-0002-5359-0281; Cittaro, Davide/0000-0003-0384-3700; Villaverde, Antonio/0000-0002-2615-4521 FU Biotechnology and Biological Sciences Research Council [BBS/E/B/0000S178] NR 21 TC 3 Z9 3 U1 0 U2 10 PU GENOMIC STAND CONSORT PI EAST LANSING PA MICHIGAN STATE UNIV, GEEO GARRITY, DEPT MICROBIOL, 6162 BIOMED & PHYS SCI BLDG, EAST LANSING, MI 48824 USA SN 1944-3277 J9 STAND GENOMIC SCI JI Stand. Genomic Sci. PY 2011 VL 5 IS 2 BP 195 EP 197 DI 10.4056/sigs.1834511 PG 3 WC Genetics & Heredity; Microbiology SC Genetics & Heredity; Microbiology GA 874GV UT WOS:000298944300002 PM 22180821 ER PT J AU Bobb, JF Scharfstein, DO Daniels, MJ Collins, FS Kelada, S AF Bobb, Jennifer F. Scharfstein, Daniel O. Daniels, Michael J. Collins, Francis S. Kelada, Samir TI Multiple Imputation of Missing Phenotype Data for QTL Mapping SO STATISTICAL APPLICATIONS IN GENETICS AND MOLECULAR BIOLOGY LA English DT Article DE multiple imputation; missing data; quantitative trait loci ID QUANTITATIVE TRAIT LOCI; AIRWAY RESPONSIVENESS; COLLABORATIVE CROSS; SYSTEMS GENETICS; INCOMPLETE DATA; MOUSE; MICE; PLETHYSMOGRAPHY; FRAMEWORK; RESOURCE AB Missing phenotype data can be a major hurdle to mapping quantitative trait loci (QTL). Though in many cases experiments may be designed to minimize the occurrence of missing data, it is often unavoidable in practice; thus, statistical methods to account for missing data are needed. In this paper we describe an approach for conjoining multiple imputation and QTL mapping. Methods are applied to map genes associated with increased breathing effort in mice after lung inflammation due to allergen challenge in developing lines of the Collaborative Cross, a new mouse genetics resource. Missing data poses a particular challenge in this study because the desired phenotype summary to be mapped is a function of incompletely observed dose-response curves. Comparison of the multiple imputation approach to two naive approaches for handling missing data suggest that these simpler methods may yield poor results: ignoring missing data through a complete case analysis may lead to incorrect conclusions, while using a last observation carried forward procedure, which does not account for uncertainty in the imputed values, may lead to anti-conservative inference. The proposed approach is widely applicable to other studies with missing phenotype data. C1 [Bobb, Jennifer F.; Scharfstein, Daniel O.] Johns Hopkins Bloomberg Sch Publ Hlth, Baltimore, MD 21205 USA. [Daniels, Michael J.] Univ Florida, Gainesville, FL 32611 USA. [Collins, Francis S.; Kelada, Samir] NHGRI, NIH, Bethesda, MD USA. RP Bobb, JF (reprint author), Johns Hopkins Bloomberg Sch Publ Hlth, Baltimore, MD 21205 USA. FU National Institutes of Health [R01 CA85295]; National Institute of Environmental Health Sciences [T32ES012871]; National Human Genome Research Institute FX We thank our collaborators Fernando Pardo Manuel de Villena, Elissa Chesler, Darla Miller, and Ginger Shaw for use of the preCC mice; Gary Churchill, David Aylor and Will Valdar for advice regarding analysis approaches; and David Schwartz for input on the allergen model. This work is supported in part by Award Numbers R01 CA85295 of the National Institutes of Health, T32ES012871 from the National Institute of Environmental Health Sciences, and the Intramural Research Program at the National Human Genome Research Institute. NR 35 TC 4 Z9 4 U1 0 U2 1 PU BERKELEY ELECTRONIC PRESS PI BERKELEY PA 2809 TELEGRAPH AVENUE, STE 202, BERKELEY, CA 94705 USA SN 1544-6115 J9 STAT APPL GENET MOL JI Stat. Appl. Genet. Mol. Biol. PY 2011 VL 10 IS 1 AR 29 DI 10.2202/1544-6115.1676 PG 29 WC Biochemistry & Molecular Biology; Mathematical & Computational Biology; Statistics & Probability SC Biochemistry & Molecular Biology; Mathematical & Computational Biology; Mathematics GA 787KQ UT WOS:000292375400001 ER PT J AU Yan, LK Liu, AY Li, ZH Zheng, G AF Yan, Lihan K. Liu, Aiyi Li, Zhaohai Zheng, Gang TI Optimal two-stage sequential robust design for gene-intervention studies SO STATISTICS AND ITS INTERFACE LA English DT Article DE Optimal two-stage design; MAX; Group sequential; Gene-intervention ID GENOME-WIDE ASSOCIATION; CLINICAL-TRIALS; SAMPLE-SIZE; TREND TESTS; PROPORTIONS; STATISTICS; MAXIMUM; MARKERS; POWER AB Gene-intervention studies investigate the responsiveness to therapies according to individuals' genetic profiles. We propose a two-stage sequential design for these studies and investigate the cost of the sample size versus the statistical power. In a typical sequential design, a single normally distributed test statistic is used. For a genetic study, the robust test is used because of the uncertainty of the underlying genetic model (e. g. the recessive, additive or dominant models). The robust test statistic that we consider in the two-stage sequential design is the maximum of three correlated normally distributed statistics, each which is optimal under the corresponding genetic model. We study various factors that affect minimizing the average sample number (ASN) or maximizing the power of a gene-intervention study under the two-stage sequential design and make recommendations for the optimal solutions under different scenarios. C1 [Yan, Lihan K.] US FDA, Off Biostat & Epidemiol, Ctr Biol Evaluat & Res, Rockville, MD 20857 USA. [Liu, Aiyi] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Biostat & Bioinformat Branch, Rockville, MD USA. [Li, Zhaohai] George Washington Univ, Dept Stat, Washington, DC 20052 USA. [Zheng, Gang] NHLBI, Off Biostat Res, Bethesda, MD 20892 USA. RP Yan, LK (reprint author), US FDA, Off Biostat & Epidemiol, Ctr Biol Evaluat & Res, Rockville, MD 20857 USA. EM lihan.yan@fda.hhs.gov; liua@mail.nih.gov; zli@gwu.edu; zhengg@nhlbi.nih.gov OI Liu, Aiyi/0000-0002-6618-5082 FU Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health FX We would like to thank the reviewers for their helpful comments which strengthened the presentation of this paper. We would also like to thank Ms. Heather Liu for her editorial help. Research of A. Liu is supported by the Intramural Research Program of the Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health. The opinions expressed in the article are those of the authors, not necessarily of the National Institutes of Health, nor the Food and Drug Administration. NR 36 TC 0 Z9 0 U1 0 U2 0 PU INT PRESS BOSTON, INC PI SOMERVILLE PA PO BOX 43502, SOMERVILLE, MA 02143 USA SN 1938-7989 EI 1938-7997 J9 STAT INTERFACE JI Stat. Interface PY 2011 VL 4 IS 4 BP 431 EP 441 PG 11 WC Mathematical & Computational Biology; Mathematics, Interdisciplinary Applications SC Mathematical & Computational Biology; Mathematics GA 861DY UT WOS:000298000500002 ER PT J AU Chen, BE Graubard, BI Flegal, KM Gail, MH AF Chen, Bingshu E. Graubard, Barry I. Flegal, Katherine M. Gail, Mitchell H. TI Comparing strategies to estimate the association of obesity with mortality via a Markov model SO STATISTICS AND ITS INTERFACE LA English DT Article DE Causation; Markov chain; Mortality; Obesity; Reverse causation ID BODY-MASS INDEX; DEATHS; UNDERWEIGHT; OVERWEIGHT; WEIGHT AB We used a first order discrete Markov model to investigate strategies to obtain unbiased estimates of the relative mortality hazard for comparing obese with non-obese participants. This hazard ratio is confounded by the fact that obese participants can be either sick or well, as can non-obese participants, and participants can migrate over time from their initial classification on obesity and health status. The parameters of the model were estimated from national survey data and used to illustrate different analytic approaches. The purpose was to compare analytic approaches and not to provide an analysis of a particular data set. Under this model, short term health-stratum-specific estimates are unbiased for estimating the health-stratum-specific instantaneous mortality hazard ratios from obesity, and updating information on body mass index and disease status during long term follow-up reduces bias. For follow-up over 10 or 20 years, exclusion of participants with preexisting disease, excluding the first five years of follow-up, and methods of analysis that ignore health status yield biased estimates of the instantaneous mortality hazard ratios. However, over 10 or 20 year time periods, long-term average mortality hazard ratios or cumulative mortality relative risks are a better reflection of the total impact of obesity, including its tendency to accelerate transitions to sickness under this model, than are instantaneous mortality hazard ratios. Over these longer time periods, average relative hazard estimates or cumulative mortality relative risks based on initially well participants, on initially sick participants, and on the combined initial population each provide valuable descriptions of associations of obesity with mortality. C1 [Chen, Bingshu E.] Queens Univ, NCIC Clin Trials Grp, Kingston, ON, Canada. [Chen, Bingshu E.] Queens Univ, Dept Community Hlth & Epidemiol, Kingston, ON, Canada. [Graubard, Barry I.; Gail, Mitchell H.] NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. [Flegal, Katherine M.] Ctr Dis Control & Prevent, Natl Ctr Hlth Stat, Hyattsville, MD 20782 USA. RP Chen, BE (reprint author), Queens Univ, NCIC Clin Trials Grp, Kingston, ON, Canada. EM bechen@ctg.queensu.ca RI Flegal, Katherine/A-4608-2013; OI Chen, Bingshu/0000-0001-6139-0696; Flegal, Katherine/0000-0002-0838-469X FU Natural Sciences and Engineering Research Council of Canada (NSERC); National Cancer Institute FX This work was supported in part by the the Natural Sciences and Engineering Research Council of Canada (NSERC).; This work was supported in part by the Intramural Research Program of the National Cancer Institute. NR 18 TC 0 Z9 0 U1 0 U2 3 PU INT PRESS BOSTON, INC PI SOMERVILLE PA PO BOX 43502, SOMERVILLE, MA 02143 USA SN 1938-7989 J9 STAT INTERFACE JI Stat. Interface PY 2011 VL 4 IS 4 BP 451 EP 461 PG 11 WC Mathematical & Computational Biology; Mathematics, Interdisciplinary Applications SC Mathematical & Computational Biology; Mathematics GA 861DY UT WOS:000298000500004 ER PT J AU Hasebe, T Buchholz, DR Shi, YB Ishizuya-Oka, A AF Hasebe, Takashi Buchholz, Daniel R. Shi, Yun-Bo Ishizuya-Oka, Atsuko TI Epithelial-Connective Tissue Interactions Induced by Thyroid Hormone Receptor Are Essential for Adult Stem Cell Development in the Xenopus laevis Intestine SO STEM CELLS LA English DT Article DE Thyroid hormone receptor; Transgenic frog; Organ culture; Tissue interaction; Intestinal remodeling ID MATRIX-METALLOPROTEINASE STROMELYSIN-3; ACID-BINDING PROTEIN; EXTRACELLULAR-MATRIX; GENE-EXPRESSION; SONIC HEDGEHOG; AMPHIBIAN METAMORPHOSIS; SIGNALING PATHWAY; TADPOLE INTESTINE; PROGENITOR CELLS; APOPTOSIS AB In the amphibian intestine during metamorphosis, stem cells appear and generate the adult absorptive epithelium, analogous to the mammalian one, under the control of thyroid hormone (TH). We have previously shown that the adult stem cells originate from differentiated larval epithelial cells in the Xenopus laevis intestine. To clarify whether TH signaling in the epithelium alone is sufficient for inducing the stem cells, we have now performed tissue recombinant culture experiments using transgenic X. laevis tadpoles that express a dominant-positive TH receptor (dpTR) under a control of heat shock promoter. Wild-type (Wt) or dpTR transgenic (Tg) larval epithelium (Ep) was isolated from the tadpole intestine, recombined with homologous or heterologous nonepithelial tissues (non-Ep), and then cultivated in the absence of TH with daily heat shocks to induce transgenic dpTR expression. Adult epithelial progenitor cells expressing sonic hedgehog became detectable on day 5 in both the recombinant intestine of Tg Ep and Tg non-Ep (Tg/Tg) and that of Tg Ep and Wt non-Ep (Tg/Wt). However, in Tg/Wt intestine, they did not express other stem cell markers such as Musashi-1 and never generated the adult epithelium expressing a marker for absorptive epithelial cells. Our results indicate that, while it is unclear why some larval epithelial cells dedifferentiate into adult progenitor/stem cells, TR-mediated gene expression in the surrounding tissues other than the epithelium is required for them to develop into adult stem cells, suggesting the importance of TH-inducible epithelial-connective tissue interactions in establishment of the stem cell niche in the amphibian intestine. STEM CELLS 2011;29:154-161 C1 [Ishizuya-Oka, Atsuko] Nippon Med Sch, Dept Biol, Nakahara Ku, Kanagawa 2110063, Japan. [Buchholz, Daniel R.] Univ Cincinnati, Dept Biol Sci, Cincinnati, OH 45221 USA. [Shi, Yun-Bo] NICHHD, Lab Gene Regulat & Dev, NIH, Bethesda, MD 20892 USA. RP Ishizuya-Oka, A (reprint author), Nippon Med Sch, Dept Biol, Nakahara Ku, 2-297-2 Kosugi Cho, Kanagawa 2110063, Japan. EM a-oka@nms.ac.jp FU JSPS [20570060]; NICHD, NIH FX We thank Dr. Kosuke Kawamura for his kind care to Tg tadpoles and Mitsuko Kajita for her technical help. This work was supported in part by the JSPS Grants-in-Aid for Scientific Research (C) (Grant number 20570060 to A.I.-O.) and in part by the Intramural Research Program of NICHD, NIH (to Y.-B.S.). NR 52 TC 25 Z9 25 U1 0 U2 3 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1066-5099 J9 STEM CELLS JI Stem Cells PD JAN PY 2011 VL 29 IS 1 BP 154 EP 161 DI 10.1002/stem.560 PG 8 WC Cell & Tissue Engineering; Biotechnology & Applied Microbiology; Oncology; Cell Biology; Hematology SC Cell Biology; Biotechnology & Applied Microbiology; Oncology; Hematology GA 712IF UT WOS:000286659300017 PM 21280164 ER PT J AU Boheler, KR Joodi, RN Qiao, H Juhasz, O Urick, AL Chuppa, SL Gundry, RL Wersto, RP Zhou, R AF Boheler, Kenneth R. Joodi, Robert N. Qiao, Hui Juhasz, Ondrej Urick, Amanda L. Chuppa, Sandra L. Gundry, Rebekah L. Wersto, Robert P. Zhou, Rong TI Embryonic Stem Cell-Derived Cardiomyocyte Heterogeneity and the Isolation of Immature and Committed Cells for Cardiac Remodeling and Regeneration SO STEM CELLS INTERNATIONAL LA English DT Article AB Pluripotent stem cells represent one promising source for cell replacement therapy in heart, but differentiating embryonic stem cell-derived cardiomyocytes (ESC-CMs) are highly heterogeneous and show a variety of maturation states. In this study, we employed an ESC clonal line that contains a cardiac-restricted ncx1 promoter-driven puromycin resistance cassette together with a mass culture system to isolate ESC-CMs that display traits characteristic of very immature CMs. The cells display properties of proliferation, CM-restricted markers, reduced mitochondrial mass, and hypoxia-resistance. Following transplantation into rodent hearts, bioluminescence imaging revealed that immature cells, but not more mature CMs, survived for at least one month following injection. These data and comparisons with more mature cells lead us to conclude that immature hypoxia resistant ESC-CMs can be isolated in mass in vitro and, following injection into heart, form grafts that may mediate long-term recovery of global and regional myocardial contractile function following infarction. C1 [Boheler, Kenneth R.; Juhasz, Ondrej] NIA, Mol Cardiol & Stem Cell Unit, Cardiovasc Sci Lab, NIH, Baltimore, MD 21224 USA. [Joodi, Robert N.] Univ Med & Dent New Jersey, Robert Wood Johnson Med Sch, Camden, NJ 08103 USA. [Joodi, Robert N.; Qiao, Hui; Zhou, Rong] Univ Penn, Dept Radiol, Labs Mol Imaging, Philadelphia, PA 19104 USA. [Urick, Amanda L.; Chuppa, Sandra L.; Gundry, Rebekah L.] Med Coll Wisconsin, Dept Biochem, Milwaukee, WI 53226 USA. [Urick, Amanda L.; Chuppa, Sandra L.; Gundry, Rebekah L.] Med Coll Wisconsin, Biotechnol & Bioengn Ctr, Milwaukee, WI 53226 USA. [Wersto, Robert P.] NIA, Resource Res Branch, NIH, Baltimore, MD 21224 USA. [Zhou, Rong] Univ Penn, Dept Bioengn, Philadelphia, PA 19104 USA. [Zhou, Rong] Univ Penn, Cardiovasc Inst, Philadelphia, PA 19104 USA. RP Boheler, KR (reprint author), NIA, Mol Cardiol & Stem Cell Unit, Cardiovasc Sci Lab, NIH, Baltimore, MD 21224 USA. EM bohelerk@grc.nia.nih.gov FU NIH [R21EB-2473, 4R00HL094798-03, R01-HL081185, R01-HL081185S1]; Innovation Center at the Medical College of Wisconsin; NIH, National Institute on Aging FX The research was supported by NIH Grants R21EB-2473 (RZ), 4R00HL094798-03 (RLG), R01-HL081185 (RZ), R01-HL081185S1 (RZ) the Innovation Center at the Medical College of Wisconsin (RLG), and the Intramural Research Program (IRP) of the NIH, National Institute on Aging (KRB, RPW). The authors also thank Dr. M. Celeste Simon for helping with hypoxic studies. NR 46 TC 3 Z9 3 U1 0 U2 1 PU HINDAWI PUBLISHING CORPORATION PI NEW YORK PA 410 PARK AVENUE, 15TH FLOOR, #287 PMB, NEW YORK, NY 10022 USA SN 1687-966X J9 STEM CELLS INT JI Stem Cells Int. PY 2011 AR UNSP 214203 DI 10.4061/2011/214203 PG 10 WC Cell & Tissue Engineering SC Cell Biology GA V29PM UT WOS:000208760300008 ER PT J AU Kania, G Boheler, KR Landmesser, U Wojakowski, W AF Kania, Gabriela Boheler, Kenneth R. Landmesser, Ulf Wojakowski, Wojciech TI Stem Cells in Heart Failure SO STEM CELLS INTERNATIONAL LA English DT Editorial Material C1 [Kania, Gabriela] Univ Zurich, Inst Physiol, CH-8057 Zurich, Switzerland. [Boheler, Kenneth R.] NIA, NIH, GRC, LCS, Baltimore, MD 21224 USA. [Landmesser, Ulf] Univ Zurich Hosp, Dept Cardiol, CH-8091 Zurich, Switzerland. [Wojakowski, Wojciech] Med Univ Silesia, Div Cardiol, PL-40583 Katowice, Poland. RP Kania, G (reprint author), Univ Zurich, Inst Physiol, Winterthurerstr 190, CH-8057 Zurich, Switzerland. EM gabriela.kania@uzh.ch NR 19 TC 0 Z9 0 U1 0 U2 0 PU HINDAWI PUBLISHING CORPORATION PI NEW YORK PA 410 PARK AVENUE, 15TH FLOOR, #287 PMB, NEW YORK, NY 10022 USA SN 1687-966X J9 STEM CELLS INT JI Stem Cells Int. PY 2011 AR UNSP 193918 DI 10.4061/2011/193918 PG 3 WC Cell & Tissue Engineering SC Cell Biology GA V29PM UT WOS:000208760300003 ER PT B AU Reddy, UM Willinger, M AF Reddy, Uma M. Willinger, Marian BE Spong, CY TI Classification of Stillbirths SO STILLBIRTH: PREDICTION, PREVENTION AND MANAGEMENT LA English DT Article; Book Chapter ID CLASSIFYING PERINATAL DEATH; RELEVANT CONDITION; MORTALITY; SYSTEM C1 [Reddy, Uma M.; Willinger, Marian] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, NIH, Bethesda, MD 20892 USA. RP Reddy, UM (reprint author), Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, NIH, Bethesda, MD 20892 USA. NR 16 TC 1 Z9 1 U1 0 U2 0 PU BLACKWELL SCIENCE PUBL PI OXFORD PA OSNEY MEAD, OXFORD OX2 0EL, ENGLAND BN 978-1-4443-9801-4; 978-1-4443-3706-8 PY 2011 BP 42 EP 54 D2 10.1002/9781444398038 PG 13 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA BA6JA UT WOS:000337156200004 ER PT S AU Oh, J Nislow, C AF Oh, Julia Nislow, Corey BE Williams, JA TI Signature-tagged Mutagenesis to Characterize Genes Through Competitive Selection of Bar-coded Genome Libraries SO STRAIN ENGINEERING: METHODS AND PROTOCOLS SE Methods in Molecular Biology LA English DT Article; Book Chapter DE Bar coding; Signature-tagged mutagenesis; Transposon mutagenesis; TagModules; Deletion collection ID YEAST DELETION MUTANTS; CANDIDA-ALBICANS; LARGE-SCALE; STREPTOCOCCUS-PNEUMONIAE; INSERTIONAL MUTAGENESIS; VIRULENCE GENES; FISSION YEAST; WIDE SCREEN; IDENTIFICATION; DISRUPTION AB The availability of collections of genome-wide deletion mutants greatly accelerates systematic analyses of gene function. However, each of the thousands of genes that comprise a genome must be phenotyped individually unless they can be assayed in parallel and subsequently deconvolved. To this end, unique molecular identifiers have been developed for a variety of microbes. Specifically, the addition of DNA "tags," or "bar codes," to each mutant allows all mutants in a collection to be pooled and phenotyped in parallel, greatly increasing experimental throughput. In this chapter, we provide an overview of current methodologies used to create such tagged mutant collections and outline how they can be applied to understand gene function, gene-gene interactions, and drug-gene interactions. Finally, we present a methodology that uses universal TagModules, capable of bar coding a wide range of microorganisms, and demonstrate its reduction to practice by creating tagged mutant collections in the pathogenic yeast Candida albicans. C1 [Oh, Julia] NHGRI, Genet & Mol Biol Branch, NIH, Bethesda, MD 20892 USA. [Nislow, Corey] Donnelly Ctr, Donnelly Sequencing Ctr, Toronto, ON, Canada. RP Oh, J (reprint author), NHGRI, Genet & Mol Biol Branch, NIH, Bethesda, MD 20892 USA. OI Nislow, Corey/0000-0002-4016-8874 FU CGH CDC HHS [P01 GH000205]; Canadian Institutes of Health Research [MOP-84305]; NHGRI NIH HHS [HG000205, R01 HG003317, T32 HG00044] NR 40 TC 2 Z9 2 U1 0 U2 4 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DR, STE 208, TOTOWA, NJ 07512-1165 USA SN 1064-3745 BN 978-1-61779-196-3 J9 METHODS MOL BIOL JI Methods Mol. Biol. PY 2011 VL 765 BP 225 EP 252 DI 10.1007/978-1-61779-197-0_14 D2 10.1007/978-1-61779-197-0 PG 28 WC Biochemical Research Methods; Biochemistry & Molecular Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Genetics & Heredity GA BWE71 UT WOS:000293772200014 PM 21815096 ER PT S AU Bhagwat, M Bhagwat, AA AF Bhagwat, Medha Bhagwat, Arvind A. BE Williams, JA TI Microbial Genome Analysis and Comparisons: Web-Based Protocols and Resources SO STRAIN ENGINEERING: METHODS AND PROTOCOLS SE Methods in Molecular Biology LA English DT Article; Book Chapter DE Pairwise genome comparisons; Bioinformatics tools; Microbial genome resources ID ACID RESISTANCE; DATABASE AB Fully annotated genome sequences of many microorganisms are publicly available as a resource. However, in-depth analysis of these genomes using specialized tools is required to derive meaningful information. We describe here the utility of three powerful publicly available genome databases and analysis tools. Protocols outlined here are particularly useful for performing pairwise genome comparisons between closely related microorganisms to identify similarities and unique features, for example to identify genes specific to a pathogenic strain of Escherichia coli compared to a nonpathogenic strain. C1 [Bhagwat, Medha] NIH, NIH Lib, Off Res Serv, Bethesda, MD 20892 USA. [Bhagwat, Arvind A.] USDA, Environm Microbial & Food Safety Lab, Beltsville, MD 20705 USA. [Bhagwat, Arvind A.] Org USDA ARS, Div Environm Microbial & Food Safety Lab, Beltsville, MD USA. RP Bhagwat, M (reprint author), NIH, NIH Lib, Off Res Serv, Bldg 10, Bethesda, MD 20892 USA. NR 14 TC 0 Z9 0 U1 0 U2 0 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DR, STE 208, TOTOWA, NJ 07512-1165 USA SN 1064-3745 BN 978-1-61779-196-3 J9 METHODS MOL BIOL JI Methods Mol. Biol. PY 2011 VL 765 BP 297 EP 307 DI 10.1007/978-1-61779-197-0_17 D2 10.1007/978-1-61779-197-0 PG 11 WC Biochemical Research Methods; Biochemistry & Molecular Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Genetics & Heredity GA BWE71 UT WOS:000293772200017 PM 21815099 ER PT J AU Roper, JA O'Carroll, AM Young, WS Lolait, SJ AF Roper, J. A. O'Carroll, A-M Young, W. S., III Lolait, S. J. TI The vasopressin Avpr1b receptor: Molecular and pharmacological studies SO STRESS-THE INTERNATIONAL JOURNAL ON THE BIOLOGY OF STRESS LA English DT Review DE Aggression; hypothalamic-pituitary-adrenal axis; stress; Avpr1b receptor; Avpr1b antagonist; vasopressin ID PITUITARY-ADRENAL AXIS; CORTICOTROPIN-RELEASING HORMONE; INSULIN-INDUCED HYPOGLYCEMIA; DEFICIENT BRATTLEBORO RATS; MESSENGER-RIBONUCLEIC-ACID; STRESS-RELATED DISORDERS; CENTRAL-NERVOUS-SYSTEM; ARGININE-VASOPRESSIN; V-1B RECEPTOR; V1B RECEPTOR AB The distribution, pharmacology and function of the arginine vasopressin (Avp) 1b receptor subtype (Avpr1b) has proved more challenging to investigate compared to other members of the Avp receptor family. Avp is increasingly recognised as an important modulator of the hypothalamic-pituitary-adrenal (HPA) axis, an action mediated by the Avpr1b present on anterior pituitary corticotrophs. The Avpr1b is also expressed in some peripheral tissues including pancreas and adrenal, and in the hippocampus (HIP), paraventricular nucleus and olfactory bulb of the rodent brain where its function is unknown. The central distribution of Avpr1bs is far more restricted than that of the Avpr1a, the main Avp receptor subtype found in the brain. Whether Avpr1b expression in rodent tissues is dependent on differences in the length of microsatellite dinucleotide repeats present in the 5' promoter region of the Avpr1b gene remains to be determined. One difficulty of functional studies on the Avpr1b, especially its involvement in the HPA axis response to stress, which prompted the generation of Avpr1b knockout (KO) mouse models, was the shortage of commercially available Avpr1b ligands, particularly antagonists. Research on mice lacking functional Avpr1bs has highlighted behavioural deficits in social memory and aggression. The Avpr1b KO also appears to be an excellent model to study the contribution of the Avpr1b in the HPA axis response to acute and perhaps some chronic (repeated) stressors where corticotrophin-releasing hormone and other genes involved in the HPA axis response to stress do not appear to compensate for the loss of the Avpr1b. C1 [Roper, J. A.; O'Carroll, A-M; Lolait, S. J.] Univ Bristol, Henry Wellcome LINE, Bristol BS1 3NY, Avon, England. [Young, W. S., III] NIMH, Sect Neural Gene Express, Dept Hlth & Human Serv, NIH, Bethesda, MD 20892 USA. RP Lolait, SJ (reprint author), Univ Bristol, Henry Wellcome LINE, Dorothy Hodgkin Bldg,Whitson St, Bristol BS1 3NY, Avon, England. EM s.j.lolait@bristol.ac.uk RI Young, W Scott/A-9333-2009 OI Young, W Scott/0000-0001-6614-5112 FU Neuroendocrinology Charitable Trust (UK); Schering-Plough Corporation; Wellcome Trust; BBSRC; NIMH [Z01-MH-002498-21] FX J.A.R received funding from the Neuroendocrinology Charitable Trust (UK) and the Schering-Plough Corporation; A.M.O'C received funding from the Wellcome Trust and BBSRC. This research was supported by the NIMH Intramural Research Program (Z01-MH-002498-21). S.J.L received funding from the Wellcome Trust. NR 136 TC 34 Z9 35 U1 1 U2 10 PU INFORMA HEALTHCARE PI LONDON PA TELEPHONE HOUSE, 69-77 PAUL STREET, LONDON EC2A 4LQ, ENGLAND SN 1025-3890 J9 STRESS JI Stress PD JAN PY 2011 VL 14 IS 1 BP 98 EP 115 DI 10.3109/10253890.2010.512376 PG 18 WC Behavioral Sciences; Endocrinology & Metabolism; Neurosciences SC Behavioral Sciences; Endocrinology & Metabolism; Neurosciences & Neurology GA 696DP UT WOS:000285422400013 PM 20828336 ER PT J AU Ginsberg, MD Palesch, YY Martin, RH Hill, MD Moy, CS Waldman, BD Yeatts, SD Tamariz, D Ryckborst, K AF Ginsberg, Myron D. Palesch, Yuko Y. Martin, Renee H. Hill, Michael D. Moy, Claudia S. Waldman, Bonnie D. Yeatts, Sharon D. Tamariz, Diego Ryckborst, Karla CA ALIAS Investigators TI The Albumin in Acute Stroke (ALIAS) Multicenter Clinical Trial Safety Analysis of Part 1 and Rationale and Design of Part 2 SO STROKE LA English DT Article DE albumin; ischemic stroke; neuroprotectant; randomized controlled trial ID FOCAL CEREBRAL-ISCHEMIA; MARKED NEUROPROTECTIVE EFFICACY; LOCAL VASCULAR DYNAMICS; DOSE-ESCALATION; BRAIN-INJURY; PILOT TRIAL; RAT MODEL; THERAPY; RESPONSES; THROMBOSIS AB Background and Purpose-Enrollment in the Albumin in Acute Stroke (ALIAS) Trial was suspended in late 2007 due to a safety concern. We present the safety data of that Trial ("Part 1") and the rationale for the design of Part 2. Methods-ALIAS Part 1 was designed to assess whether 25% albumin (ALB) started within 5 hours of stroke onset would confer neuroprotection in subjects with acute ischemic stroke and baseline National Institutes of Health Stroke Scale of >= 6. Exclusion criteria included recent or current congestive heart failure, myocardial infarction, or cardiac surgery. The study comprised 2 cohorts: subjects who received thrombolysis and those who did not, each with 1:1 randomization to ALB or placebo. The primary outcome was the National Institutes of Health Stroke Scale and modified Rankin Scales at 90 days. The intended sample size was 1800. Results-Four hundred thirty-four subjects were enrolled, and 424 were used in the safety analysis (ALB 207, saline 217). There were 36 deaths within the first 30 days in the ALB group and 21 in the saline group. In contrast, death rates after 30 days were similar by treatment. Large strokes were the predominant cause of early death in both groups. In subjects >83 years of age, 90-day death rates were 2.3-fold higher with ALB than with saline (95% CI, 1.04 to 5.12). Similarly, 90-day deaths in subjects receiving excessive fluids were 2.10-fold greater with ALB than with saline (CI, 1.10 to 3.98). Conclusions-The ALIAS Part 2 Trial, which started in early 2009, was modified as follows to enhance safety: upper age limit of 83 years; requirement for normal baseline serum troponin level; restriction of total intravenous fluids in the first 48 hours to <= 4200 mL; mandatory diuretic at 12 to 24 hours; and detailed site retraining. Because of insufficient nonthrombolysed subjects (22%) in Part 1, the 2-cohort design was eliminated. The Data Safety Monitoring Board has reviewed the safety data of Part 2 3 times and has approved continuation of the trial. (Stroke. 2011;42:119-127.) C1 [Ginsberg, Myron D.; Tamariz, Diego] Univ Miami, Miller Sch Med, Dept Neurol, Miami, FL 33101 USA. [Hill, Michael D.; Ryckborst, Karla] Univ Calgary, Foothills Med Ctr, Calgary, AB, Canada. [Hill, Michael D.] Univ Calgary, Dept Clin Neurosci, Calgary, AB, Canada. [Palesch, Yuko Y.; Martin, Renee H.; Waldman, Bonnie D.; Yeatts, Sharon D.] Med Univ S Carolina, Dept Med, Div Biostat & Epidemiol, Charleston, SC 29425 USA. [Moy, Claudia S.] NINDS Off Clin Res, Bethesda, MD USA. RP Ginsberg, MD (reprint author), Univ Miami, Miller Sch Med, Dept Neurol D4 5, POB 016960, Miami, FL 33101 USA. EM mginsberg@med.miami.edu OI Hill, Michael/0000-0002-6269-1543 FU National Institutes of Health [U01 NS040406, U01 NS054630] FX Supported by National Institutes of Health grants U01 NS040406 (to M.D.G.) and U01 NS054630 (to Y.Y.P.). NR 33 TC 38 Z9 41 U1 0 U2 5 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0039-2499 J9 STROKE JI Stroke PD JAN PY 2011 VL 42 IS 1 BP 119 EP 127 DI 10.1161/STROKEAHA.110.596072 PG 9 WC Clinical Neurology; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA 699AN UT WOS:000285636400027 PM 21164127 ER PT B AU Fabre, K DeGraff, W Cook, JA Krishna, MC Mitchell, JB AF Fabre, Kristin DeGraff, William Cook, John A. Krishna, Murali C. Mitchell, James B. BE Basu, S Wiklund, L TI Experimental Models for Ionizing Radiation Research SO STUDIES ON EXPERIMENTAL MODELS SE Oxidative Stress in Applied Basic Research and Clinical Practice LA English DT Article; Book Chapter DE Cell killing; DNA damage; DNA repair; IR protectors; Radiation; Radiosensitizers; ROS ID DOUBLE-STRAND BREAKS; INDUCED GENOMIC INSTABILITY; SOMATIC MAMMALIAN-CELLS; CHINESE-HAMSTER-CELLS; DNA-REPAIR; ALPHA-PARTICLES; LUNG-CANCER; INTRACELLULAR SUPEROXIDE; DEINOCOCCUS-RADIODURANS; GEL-ELECTROPHORESIS AB Ionizing radiation is a valuable tool used for cancer treatment as well as for basic molecular research. More recent interest stems from a need to provide countermeasures against accidental or intentional exposure to radiation through nuclear devices. This chapter provides an overview of the biological effects of radiation and highlights models used to study radiation-induced damage and repair. In vitro and in vivo endpoints including DNA damage, cell survival, apoptosis, cytogenetic aberrations, oxidative stress, tumor response, and genomic instability are discussed. Appropriate use of these models will facilitate the advancement of radiation research as novel molecular mechanisms are elucidated. C1 [Fabre, Kristin; DeGraff, William; Cook, John A.; Krishna, Murali C.; Mitchell, James B.] NCI, Radiat Biol Branch, Ctr Canc Res, Bethesda, MD 20892 USA. RP Krishna, MC (reprint author), NCI, Radiat Biol Branch, Ctr Canc Res, Bethesda, MD 20892 USA. EM murali@helix.nih.gov NR 127 TC 0 Z9 0 U1 0 U2 2 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013, UNITED STATES BN 978-1-60761-955-0 J9 OXID STRESS APPL BAS JI Oxid. Stress Appl. Basic Res. Clin. Pract. PY 2011 BP 371 EP 397 DI 10.1007/978-1-60761-956-7_17 D2 10.1007/978-1-60761-956-7 PG 27 WC Biochemistry & Molecular Biology; Medicine, General & Internal SC Biochemistry & Molecular Biology; General & Internal Medicine GA BVJ58 UT WOS:000291666700017 ER PT J AU Dell, CA Gust, SW MacLean, S AF Dell, Colleen Anne Gust, Steven W. MacLean, Sarah TI Global Issues in Volatile Substance Misuse INTRODUCTION SO SUBSTANCE USE & MISUSE LA English DT Editorial Material DE volatile substance misuse; inhalants; sociocultural epidemiology; neuroscience; interventions; context-specific knowledge; huffing; cuffing; chroming; bagging ID INHALANT USE; ABUSE; ADOLESCENTS AB This special issue of Substance Use & Misuse addresses the public health issue of volatile substance misuse (VSM), the inhalation of gases or vapors for psychoactive effects, assessing the similarities and differences in the products misused, patterns, prevalence, etiologies, and impacts of VSM by examining it through sociocultural epidemiology, neuroscience, and interventions research. The Canadian, US, and Australian guest editors contend that, when compared with other drugs used at a similar prevalence, VSM has attracted relatively little research effort. The authors and editors call for further research to develop evidence-based policies and comprehensive interventions that respect culture and context-specific knowledge.0.35 and >2.0 ng/mL/y have been associated with an increased risk of prostate cancer (CaP) death more than 10 years and 1 year before diagnosis, respectively. It is unknown how frequently PSAVs of this magnitude occur in community men. METHODS From the Baltimore Longitudinal Study of Aging, we examined the PSAV distribution in 786 men with serial PSA measurements (3474 PSAV observations) at total PSA levels <10 ng/mL. We also determined whether PSAV altered the probability of overall and life-threatening CaP at PSA levels <3 and 3-10 ng/mL. RESULTS Overall, the mean PSA and PSAV were 1.3 ng/mL and 0.05 ng/mL/y, respectively. PSAV rose continuously with increasing PSA (P < .0001), and was significantly higher in cancers than controls for observations at PSA levels <3 ng/mL (P = .02) and 3-10 ng/mL (P = .0008). The probability of life-threatening CaP was 3% at a PSA <3 ng/mL, but increased to 13.6% with PSAV >0.4 ng/mL/y. At PSA levels of 3-10 ng/mL, the probability of life-threatening CaP was 9.8% based on PSA alone vs 12% with PSAV >0.4 ng/mL/y. CONCLUSIONS PSAV was significantly higher in CaP observations than controls in all PSA ranges studied and altered the risk of overall and life-threatening CaP at a given PSA level. Because the value of PSAV is PSA-dependent, the PSA level should be taken into account when interpreting PSAV. UROLOGY 77: 143-148, 2011. (C) 2011 Published by Elsevier Inc. C1 Johns Hopkins Med Inst, James Buchanan Brady Urol Inst, Baltimore, MD 21205 USA. NIA, NIH, Clin Res Branch, Baltimore, MD 21224 USA. RP Loeb, S (reprint author), Johns Hopkins Brady Urol Inst, 600 N Wolfe St,Marburg 1, Baltimore, MD 21287 USA. EM stacyloeb@gmail.com OI Loeb, Stacy/0000-0003-3933-9207 FU NIH, National Institute on Aging FX This research was supported by the Intramural Research Program of the NIH, National Institute on Aging. NR 19 TC 10 Z9 10 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0090-4295 J9 UROLOGY JI Urology PD JAN PY 2011 VL 77 IS 1 BP 143 EP 147 DI 10.1016/j.urology.2010.04.068 PG 5 WC Urology & Nephrology SC Urology & Nephrology GA 700XM UT WOS:000285778800044 PM 21195835 ER PT S AU Griffon, N Soualmia, LF Neveol, A Massari, P Thirion, B Dahamna, B Darmoni, SJ AF Griffon, Nicolas Soualmia, Lina F. Neveol, Aurelie Massari, Philippe Thirion, Benoit Dahamna, Badisse Darmoni, Stefan J. BE Moen, A Andersen, SK Aarts, J Hurlen, P TI Evaluation of Multi-Terminology Super-Concepts for Information Retrieval SO USER CENTRED NETWORKED HEALTH CARE SE Studies in Health Technology and Informatics LA English DT Proceedings Paper CT 23 rd Conference of the European Federation of Medical Informatics (MIE) CY AUG 28-31, 2011 CL Forum Databehandling Helsesektoren, Oslo, NORWAY SP European Federat Med Informat HO Forum Databehandling Helsesektoren DE abstracting and indexing; cataloguing; information storage and retrieval; internet; controlled vocabulary AB Background: Following a recent change in the indexing policy for French quality controlled health gateway CISMeF, multiple terminologies are now being used for indexing in addition to MeSH (R). Objective: To evaluate precision and recall of super-concepts for information retrieval in a multi-terminology paradigm compared to MeSH-only. Methods: We evaluate the relevance of resources retrieved by multi-terminology super-concepts and MeSH-only super-concepts queries. Results: Recall was 8-14% higher for multi-terminology super-concepts compared to MeSH only super-concepts. Precision decreased from 0.66 for MeSH only super-concepts to 0.61 for multi-terminology super-concepts. Retrieval performance was found to vary significantly depending on the super-concepts (p<10(-4)) and indexing methods (manual vs automatic; p<0.004). Conclusion: A multi-terminology paradigm contributes to increase recall but lowers precision. Automated tools for indexing are not accurate enough to allow a very precise information retrieval. C1 [Griffon, Nicolas; Massari, Philippe; Thirion, Benoit; Dahamna, Badisse; Darmoni, Stefan J.] Rouen Univ Hosp, CISMeF, 1 Rue Germont, F-76031 Rouen, France. [Soualmia, Lina F.; Thirion, Benoit; Dahamna, Badisse; Darmoni, Stefan J.] Univ Rouen, BTIBS LITIS, EA 4108, Rouen, France. [Soualmia, Lina F.] Univ Paris 13, LIM&Bio, F-93430 Villetaneuse, France. [Neveol, Aurelie] NLM, Natl Ctr Biotechnol Informat, Bethesda, MD 20894 USA. RP Darmoni, SJ (reprint author), Rouen Univ Hosp, CISMeF, 1 Rue Germont, F-76031 Rouen, France. EM stefan.darmoni@chu-rouen.fr RI Stefan, Darmoni/H-4554-2016; OI Soualmia, Lina F/0000-0001-7668-2819 NR 10 TC 1 Z9 1 U1 0 U2 0 PU IOS PRESS PI AMSTERDAM PA NIEUWE HEMWEG 6B, 1013 BG AMSTERDAM, NETHERLANDS SN 0926-9630 BN 978-1-60750-806-9 J9 STUD HEALTH TECHNOL PY 2011 VL 169 BP 492 EP 496 DI 10.3233/978-1-60750-806-9-492 PG 5 WC Health Care Sciences & Services; Medical Informatics SC Health Care Sciences & Services; Medical Informatics GA BA4DP UT WOS:000335401700096 PM 21893798 ER PT B AU Keith, JM AF Keith, Jerry M. BE Rappuoli, R Bagnoli, F TI Bacterial Protein Toxins Used in Vaccines SO VACCINE DESIGN: INNOVATIVE APPROACHES AND NOVEL STRATEGIES LA English DT Article; Book Chapter ID ACELLULAR PERTUSSIS VACCINES; SITE-DIRECTED MUTAGENESIS; TOBACCO MOSAIC VIRUS; AMINO-ACID-SEQUENCE; DIPHTHERIA-TOXIN; TETANUS TOXIN; BORDETELLA-PERTUSSIS; WHOOPING-COUGH; NUCLEOTIDE-SEQUENCE; ESCHERICHIA-COLI AB At first glance, the idea of using protein toxins as vaccines against bacterial human diseases seems somewhat of a paradox. However, in some diseases, the severe pathological effects manifested by the causative agents are mediated entirely by protein toxins. Thus, it seems reasonable to expect that if antibodies could be induced against the protein toxin, they should be effective at preventing severe disease. Of course, the obvious challenge is to detoxify the protein toxin activity without destroying its ability to induce neutralizing antibodies. From an academic point of view, it is ironic that early vaccines against diphtheria, tetanus, and whooping cough were successful without understanding what made them work. One of the keys to this puzzle was uncovered quite by accident when it was discovered that diphtheria toxin stock preparations stored in large earthenware jars too large to be autoclaved were being detoxified by the residual formalin that leached into the preparations from the formalin-sterilized jars. It took two decades for this discovery to be understood and appreciated to a point at which formalin treatment could be applied to produce toxoid preparations for vaccination. It then took another half a century to develop the scientific tools and knowledge needed to bring forth the new generation of vaccines, which are highly effective and less reactogenic. This chapter traces the scientific history, controversies, and development of diphtheria, tetanus and pertussis vaccines. C1 Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, NIH, Bethesda, MD USA. RP Keith, JM (reprint author), Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, NIH, Bethesda, MD USA. EM keithjer@mail.nih.gov NR 199 TC 1 Z9 1 U1 0 U2 0 PU CAISTER ACADEMIC PRESS PI WYMONDHAM PA 32 HEWITTS LANE, WYMONDHAM NR 18 0JA, ENGLAND BN 978-1-904455-74-5 PY 2011 BP 109 EP 137 PG 29 WC Immunology; Microbiology SC Immunology; Microbiology GA BSI02 UT WOS:000284505400006 ER PT J AU Webster, JD Dennis, MM Dervisis, N Heller, J Bacon, NJ Bergman, PJ Bienzle, D Cassali, G Castagnaro, M Cullen, J Esplin, DG Pena, L Goldschmidt, MH Hahn, KA Henry, CJ Hellmen, E Kamstock, D Kirpensteijn, J Kitchell, BE Amorim, RL Lenz, SD Lipscomb, TP McEntee, M McGill, LD McKnight, CA McManus, PM Moore, AS Moore, PF Moroff, SD Nakayama, H Northrup, NC Sarli, G Scase, T Sorenmo, K Schulman, FY Shoieb, AM Smedley, RC Spangler, WL Teske, E Thamm, DH Valli, VE Vernau, W von Euler, H Withrow, SJ Weisbrode, SE Yager, J Kiupel, M AF Webster, J. D. Dennis, M. M. Dervisis, N. Heller, J. Bacon, N. J. Bergman, P. J. Bienzle, D. Cassali, G. Castagnaro, M. Cullen, J. Esplin, D. G. Pena, L. Goldschmidt, M. H. Hahn, K. A. Henry, C. J. Hellmen, E. Kamstock, D. Kirpensteijn, J. Kitchell, B. E. Amorim, R. L. Lenz, S. D. Lipscomb, T. P. McEntee, M. McGill, L. D. McKnight, C. A. McManus, P. M. Moore, A. S. Moore, P. F. Moroff, S. D. Nakayama, H. Northrup, N. C. Sarli, G. Scase, T. Sorenmo, K. Schulman, F. Y. Shoieb, A. M. Smedley, R. C. Spangler, W. L. Teske, E. Thamm, D. H. Valli, V. E. Vernau, W. von Euler, H. Withrow, S. J. Weisbrode, S. E. Yager, J. Kiupel, M. TI Recommended Guidelines for the Conduct and Evaluation of Prognostic Studies in Veterinary Oncology SO VETERINARY PATHOLOGY LA English DT Article DE cancer; guidelines; prognostication; standardization; veterinary oncology ID MAST-CELL TUMORS; MULTIVARIATE DATA-ANALYSIS; MINIMUM INFORMATION; SURVIVAL ANALYSIS; APPENDICULAR OSTEOSARCOMA; PROTEIN EXPRESSION; CONSORT STATEMENT; DOGS; IMMUNOHISTOCHEMISTRY; QUALITY AB There is an increasing need for more accurate prognostic and predictive markers in veterinary oncology because of an increasing number of treatment options, the increased financial costs associated with treatment, and the emotional stress experienced by owners in association with the disease and its treatment. Numerous studies have evaluated potential prognostic and predictive markers for veterinary neoplastic diseases, but there are no established guidelines or standards for the conduct and reporting of prognostic studies in veterinary medicine. This lack of standardization has made the evaluation and comparison of studies difficult. Most important, translating these results to clinical applications is problematic. To address this issue, the American College of Veterinary Pathologists' Oncology Committee organized an initiative to establish guidelines for the conduct and reporting of prognostic studies in veterinary oncology. The goal of this initiative is to increase the quality and standardization of veterinary prognostic studies to facilitate independent evaluation, validation, comparison, and implementation of study results. This article represents a consensus statement on the conduct and reporting of prognostic studies in veterinary oncology from veterinary pathologists and oncologists from around the world. These guidelines should be considered a recommendation based on the current state of knowledge in the field, and they will need to be continually reevaluated and revised as the field of veterinary oncology continues to progress. As mentioned, these guidelines were developed through an initiative of the American College of Veterinary Pathologists' Oncology Committee, and they have been reviewed and endorsed by the World Small Animal Veterinary Association. C1 [Smedley, R. C.; Kiupel, M.] Michigan State Univ, Coll Vet Med, Diagnost Ctr Populat & Anim Hlth, E Lansing, MI 48824 USA. [Webster, J. D.] NCI, Mol Pathol Unit, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. [Dennis, M. M.] Univ Sydney, Fac Vet Sci, Camden, NSW, Australia. [Dervisis, N.; Kitchell, B. E.] Michigan State Univ, Coll Vet Med, Dept Small Anim Clin Sci, E Lansing, MI 48824 USA. [Heller, J.] Charles Sturt Univ, Sch Anim & Vet Sci, Wagga Wagga, NSW, Australia. [Bacon, N. J.] Univ Florida, Coll Vet Med, Dept Small Anim Clin Sci, Gainesville, FL 32610 USA. [Bergman, P. J.] BrightHeart Vet Ctr, Armonk, NY USA. [Bienzle, D.] Univ Guelph, Dept Pathobiol, Guelph, ON N1G 2W1, Canada. [Cassali, G.] Univ Fed Minas Gerais, Inst Biol Sci, Dept Gen Pathol, Belo Horizonte, MG, Brazil. [Castagnaro, M.] Univ Padua, Dept Publ Hlth Comparat Pathol & Vet Hyg, Padua, Italy. [Cullen, J.] N Carolina State Univ, Coll Vet Med, Dept Populat Hlth & Pathobiol, Raleigh, NC USA. [Esplin, D. G.; McGill, L. D.] ARUP Labs, Salt Lake City, UT USA. [Pena, L.] Univ Complutense Madrid, Sch Vet, Dept Anim Med Surg & Pathol, Madrid, Spain. [Goldschmidt, M. H.] Univ Penn, Sch Vet Med, Dept Pathobiol, Philadelphia, PA 19104 USA. [Hahn, K. A.] Hills Pet Nutr Inc, Topeka, KS USA. [Henry, C. J.] Univ Missouri, Coll Vet Med, Dept Vet Med & Surg, Columbia, MO 65211 USA. [Hellmen, E.] Swedish Univ Agr Sci, Dept Anat Physiol & Biochem, Uppsala, Sweden. [Kamstock, D.] Colorado State Univ, Coll Vet Med, Dept Microbiol Immunol & Pathol, Ft Collins, CO 80523 USA. [Kirpensteijn, J.; Teske, E.] Univ Utrecht, Fac Vet Med, Dept Compan Anim Sci, Utrecht, Netherlands. [Amorim, R. L.] Sao Paulo State Univ, UNESP, Sch Vet Med, Dept Vet Clin, Sao Paulo, Brazil. [Lenz, S. D.] Purdue Univ, Sch Vet Med, Dept Comparat Pathobiol, W Lafayette, IN 47907 USA. [Lipscomb, T. P.; Schulman, F. Y.] Armed Forces Inst Pathol, Dept Vet Pathol, Washington, DC 20306 USA. [McEntee, M.] Cornell Univ, Coll Vet Med, Dept Clin Sci, Ithaca, NY 14853 USA. [McKnight, C. A.] MPI Res, Mattawan, MI USA. [McManus, P. M.] Idexx Reference Labs, Portland, OR USA. [Moore, A. S.] Univ Sydney, Fac Vet Sci, Sydney, NSW 2006, Australia. [Moore, P. F.; Vernau, W.] Univ Calif Davis, Sch Vet Med, Dept Pathol Microbiol & Immunol, Davis, CA 95616 USA. [Moroff, S. D.] Antech Diagnost, Lake Success, NY USA. [Nakayama, H.] Univ Tokyo, Grad Sch Agr & Life Sci, Tokyo, Japan. [Northrup, N. C.] Univ Georgia, Coll Vet Med, Dept Small Anim Med & Surg, Athens, GA USA. [Sarli, G.] Univ Bologna, Fac Vet Med, Dept Vet Publ Hlth & Anim Pathol, Bologna, Italy. [Scase, T.] Bridge Pathol Ltd, Bristol, Avon, England. [Sorenmo, K.] Univ Penn, Sch Vet Med, Ryan Vet Hosp, Philadelphia, PA 19104 USA. [Shoieb, A. M.] Pfizer Ltd, Drug Safety & Res Dev, Sandwich CT13 9NJ, Kent, England. [Spangler, W. L.] NSG Pathol, Winters, CA USA. [Thamm, D. H.; Withrow, S. J.] Colorado State Univ, Anim Canc Ctr, Ft Collins, CO 80523 USA. [Valli, V. E.] VDx Vet Diagnost, Davis, CA USA. [von Euler, H.] Swedish Univ Agr Sci, Dept Clin Sci, Uppsala, Sweden. [Weisbrode, S. E.] Ohio State Univ, Coll Vet Med, Dept Vet Biosci, Columbus, OH 43210 USA. [Yager, J.] Yager Best Histovet, Guelph, ON, Canada. [Kiupel, M.] Michigan State Univ, Coll Vet Med, Dept Pathobiol & Diagnost Invest, E Lansing, MI 48824 USA. RP Kiupel, M (reprint author), Michigan State Univ, Diagnost Ctr Populat & Anim Hlth, 4125 Beaumont Rd 152A, Lansing, MI 48910 USA. EM kiupel@dcpah.msu.edu RI Medicina Molecular, Inct/J-8737-2013; Pena, Laura/M-7820-2014; Thamm, Douglas/I-5976-2013; Heller, Jane/H-9596-2016; Dervisis, Nikolaos/K-8931-2016; OI Pena, Laura/0000-0001-7135-6280; Thamm, Douglas/0000-0002-8914-7767; Heller, Jane/0000-0003-3993-0160; Dervisis, Nikolaos/0000-0003-2869-1483; Goldschmidt, Michael/0000-0001-9515-0535; , Carolyn/0000-0002-2761-5203 FU American College of Veterinary Pathologists' Oncology Committee; World Small Animal Veterinary Association FX These guidelines were developed through an initiative of the American College of Veterinary Pathologists' Oncology Committee and represent the consensus opinion of the committee and the listed authors. The guidelines have also been reviewed and endorsed by the World Small Animal Veterinary Association. We would like to thank both organizations for their support and guidance. NR 60 TC 29 Z9 29 U1 1 U2 6 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 0300-9858 J9 VET PATHOL JI Vet. Pathol. PD JAN PY 2011 VL 48 IS 1 BP 7 EP 18 DI 10.1177/0300985810377187 PG 12 WC Pathology; Veterinary Sciences SC Pathology; Veterinary Sciences GA 719JH UT WOS:000287200500002 PM 20664014 ER PT J AU Kiupel, M Webster, JD Bailey, KL Best, S DeLay, J Detrisac, CJ Fitzgerald, SD Gamble, D Ginn, PE Goldschmidt, MH Hendrick, MJ Howerth, EW Janovitz, EB Langohr, I Lenz, SD Lipscomb, TP Miller, MA Misdorp, W Moroff, S Mullaney, TP Neyens, I O'Toole, D Ramos-Vara, J Scase, TJ Schulman, FY Sledge, D Smedley, RC Smith, K Snyder, PW Southorn, E Stedman, NL Steficek, BA Stromberg, PC Valli, VE Weisbrode, SE Yager, J Heller, J Miller, R AF Kiupel, M. Webster, J. D. Bailey, K. L. Best, S. DeLay, J. Detrisac, C. J. Fitzgerald, S. D. Gamble, D. Ginn, P. E. Goldschmidt, M. H. Hendrick, M. J. Howerth, E. W. Janovitz, E. B. Langohr, I. Lenz, S. D. Lipscomb, T. P. Miller, M. A. Misdorp, W. Moroff, S. Mullaney, T. P. Neyens, I. O'Toole, D. Ramos-Vara, J. Scase, T. J. Schulman, F. Y. Sledge, D. Smedley, R. C. Smith, K. Snyder, P. W. Southorn, E. Stedman, N. L. Steficek, B. A. Stromberg, P. C. Valli, V. E. Weisbrode, S. E. Yager, J. Heller, J. Miller, R. TI Proposal of a 2-Tier Histologic Grading System for Canine Cutaneous Mast Cell Tumors to More Accurately Predict Biological Behavior SO VETERINARY PATHOLOGY LA English DT Article DE canine; histologic grading; mast cell tumor ID MITOTIC INDEX; C-KIT; SURVIVAL; DOGS; PATHOLOGISTS; MORPHOMETRY; PROGNOSIS AB Currently, prognostic and therapeutic determinations for canine cutaneous mast cell tumors (MCTs) are primarily based on histologic grade. However, the use of different grading systems by veterinary pathologists and institutional modifications make the prognostic value of histologic grading highly questionable. To evaluate the consistency of microscopic grading among veterinary pathologists and the prognostic significance of the Patnaik grading system, 95 cutaneous MCTs from 95 dogs were graded in a blinded study by 28 veterinary pathologists from 16 institutions. Concordance among veterinary pathologists was 75% for the diagnosis of grade 3 MCTs and less than 64% for the diagnosis of grade 1 and 2 MCTs. To improve concordance among pathologists and to provide better prognostic significance, a 2-tier histologic grading system was devised. The diagnosis of high-grade MCTs is based on the presence of any one of the following criteria: at least 7 mitotic figures in 10 high-power fields (hpf); at least 3 multinucleated (3 or more nuclei) cells in 10 hpf; at least 3 bizarre nuclei in 10 hpf; karyomegaly (ie, nuclear diameters of at least 10% of neoplastic cells vary by at least two-fold). Fields with the highest mitotic activity or with the highest degree of anisokaryosis were selected to assess the different parameters. According to the novel grading system, high-grade MCTs were significantly associated with shorter time to metastasis or new tumor development, and with shorter survival time. The median survival time was less than 4 months for high-grade MCTs but more than 2 years for low-grade MCTs. C1 [Kiupel, M.] Michigan State Univ, Dept Pathobiol & Diagnost Invest, Diagnost Ctr Populat & Anim Hlth, Coll Vet Med, Lansing, MI 48910 USA. [Webster, J. D.] NCI, Mol Pathol Unit, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. [Bailey, K. L.] Amgen Inc, Seattle, WA USA. [Best, S.; Southorn, E.; Yager, J.] Yager Best Histovet, Guelph, ON, Canada. [DeLay, J.] Univ Guelph, Hlth Anim Lab, Guelph, ON N1G 2W1, Canada. [Detrisac, C. J.] Pathol Associates Inc, Charles River Labs, Chicago, IL USA. [Gamble, D.; Moroff, S.] Antech Diagnost, Lake Success, NY USA. [Ginn, P. E.] Univ Florida, Coll Vet Med, Dept Infect Dis & Pathol, Gainesville, FL USA. [Goldschmidt, M. H.; Hendrick, M. J.] Univ Penn, Sch Vet Med, Dept Pathobiol, Philadelphia, PA 19104 USA. [Howerth, E. W.] Univ Georgia, Coll Vet Med, Dept Pathol, Athens, GA 30602 USA. [Janovitz, E. B.] Bristol Myers Squibb Co, Dept Discovery Toxicol, Princeton, NJ USA. [Lenz, S. D.; Snyder, P. W.] Purdue Univ, Sch Vet Med, Dept Comparat Pathobiol, W Lafayette, IN 47907 USA. [Lipscomb, T. P.; Schulman, F. Y.] Armed Forces Inst Pathol, Dept Vet Pathol, Washington, DC 20306 USA. [Misdorp, W.] Univ Utrecht, Fac Vet Med, Dept Pathobiol, Utrecht, Netherlands. [Neyens, I.] Charles River Labs Preclin Serv Montreal Inc, Senneville, PQ, Canada. [O'Toole, D.] Univ Wyoming, Dept Vet Sci, Wyoming State Vet Lab, Laramie, WY 82071 USA. [Scase, T. J.] Bridge Pathol Ltd, Bristol, Avon, England. [Smith, K.] Univ London, Royal Vet Coll, Dept Pathol & Infect Dis, N Mymms, Herts, England. [Stedman, N. L.] Busch Gardens, Tampa, FL USA. [Stromberg, P. C.; Weisbrode, S. E.] Ohio State Univ, Coll Vet Med, Dept Vet Biosci, Columbus, OH 43210 USA. [Valli, V. E.] VDx Vet Diagnost, Davis, CA USA. [Heller, J.] Charles Sturt Univ, Sch Anim & Vet Sci, Wagga Wagga, NSW, Australia. [Miller, R.] Michigan State Univ, Coll Vet Med, Ctr Comparat Epidemiol, E Lansing, MI 48824 USA. RP Kiupel, M (reprint author), Michigan State Univ, Dept Pathobiol & Diagnost Invest, Diagnost Ctr Populat & Anim Hlth, Coll Vet Med, 4125 Beaumont Rd,Room 152A, Lansing, MI 48910 USA. EM kiupel@dcpah.msu.edu RI Heller, Jane/H-9596-2016; OI Heller, Jane/0000-0003-3993-0160; Langohr, Ingeborg/0000-0001-7366-4391; Goldschmidt, Michael/0000-0001-9515-0535 FU initiative of the American College of Veterinary Pathologists' Oncology Committee; World Small Animal Veterinary Association; College of Veterinary Medicine, Michigan State University FX We thank the clinical faculty who provided follow-up data on dogs. This study represents an initiative of the American College of Veterinary Pathologists' Oncology Committee; the manuscript was also reviewed and endorsed by the World Small Animal Veterinary Association. We thank both organizations for their support and guidance.; Funding for this study was provided in part by the Companion Animal Fund of the College of Veterinary Medicine, Michigan State University. NR 19 TC 82 Z9 84 U1 9 U2 43 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 0300-9858 J9 VET PATHOL JI Vet. Pathol. PD JAN PY 2011 VL 48 IS 1 BP 147 EP 155 DI 10.1177/0300985810386469 PG 9 WC Pathology; Veterinary Sciences SC Pathology; Veterinary Sciences GA 719JH UT WOS:000287200500012 PM 21062911 ER PT J AU Yoshii, K Igarashi, M Ito, K Kariwa, H Holbrook, MR Takashima, I AF Yoshii, Kentaro Igarashi, Manabu Ito, Kimihito Kariwa, Hiroaki Holbrook, Michael R. Takashima, Ikuo TI Construction of an infectious cDNA clone for Omsk hemorrhagic fever virus, and characterization of mutations in NS2A and NS5 SO VIRUS RESEARCH LA English DT Article DE Omsk hemorrhagic fever; Flavivirus; Infectious cDNA; Viral replication ID BORNE-ENCEPHALITIS-VIRUS; WEST-NILE-VIRUS; DEPENDENT RNA-POLYMERASE; NONSTRUCTURAL PROTEIN NS2A; DENGUE VIRUS; SECONDARY STRUCTURE; CRYSTAL-STRUCTURE; FLAVIVIRUS; STRAIN; REPLICATION AB Omsk hemorrhagic fever virus (OHFV) is a member of the tick-borne encephalitis serocomplex of flaviviruses, and causes hemorrhagic disease in humans. In this study, an infectious cDNA of OHFV was constructed to investigate the molecular mechanisms involved in OHFV pathogenesis for the first time. Our cDNA clone was capable of producing infectious virus which is genetically identical to the parental Guriev strain, and the recombinant virus showed similar biological properties to the parental virus including growth kinetics and virulence characteristics. While characterizing the cDNAs, fortuitous mutations at NS2A position 46 and NS5 position 836 were found to affect viral production. By using a viral replicon expressing luciferase, it was shown that both of the mutations produced a defect in RNA replication and that the NS5 mutation induced a temperature-sensitive phenotype, indicating the importance of these residues in RNA replication. This infectious cDNA will be a useful tool to study the replication and pathogenesis of OHFV. (C) 2010 Elsevier B.V. All rights reserved. C1 [Yoshii, Kentaro] Hokkaido Univ, Publ Hlth Lab, Grad Sch Vet Med, Kita Ku, Sapporo, Hokkaido 0600818, Japan. [Yoshii, Kentaro; Holbrook, Michael R.] Univ Texas Med Branch, Dept Pathol, Inst Human Infect & Immun, Galveston, TX 77555 USA. [Igarashi, Manabu; Ito, Kimihito] Hokkaido Univ, Dept Global Epidemiol, Res Ctr Zoonosis Control, Sapporo, Hokkaido 0010020, Japan. [Holbrook, Michael R.] NIAID Integrated Res Facil, Frederick, MD 21702 USA. RP Yoshii, K (reprint author), Hokkaido Univ, Publ Hlth Lab, Grad Sch Vet Med, Kita Ku, Kita 18 Nishi 9, Sapporo, Hokkaido 0600818, Japan. EM kyoshii@vetmed.hokudai.ac.jp RI Kariwa, Hiroaki/A-5258-2012; Ito, Kimihito/E-9975-2012; Igarashi, Manabu/F-6871-2012; YOSHII, Kentaro/A-4808-2012 OI Ito, Kimihito/0000-0003-4986-1795; FU Japan Health Sciences Foundation; Ministry of Education, Science, Sports, and Culture of Japan; Ministry of Health, Labour, and Welfare of Japan; Western Regional Center of Excellence [U54 AI057156] FX This work was supported by Overseas Assignment Program for Japanese Researchers in Research into Emerging and Re-emerging Infectious Diseases from The Japan Health Sciences Foundation and Grants-in-Aid for Scientific Research from the Ministry of Education, Science, Sports, and Culture of Japan, Health Sciences Grants for Research on Emerging and Re-emerging Infectious Disease from the Ministry of Health, Labour, and Welfare of Japan, and a Western Regional Center of Excellence (U54 AI057156) Career Development award (MRH) in part. NR 55 TC 11 Z9 11 U1 1 U2 3 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0168-1702 J9 VIRUS RES JI Virus Res. PD JAN PY 2011 VL 155 IS 1 BP 61 EP 68 DI 10.1016/j.virusres.2010.08.023 PG 8 WC Virology SC Virology GA 716YV UT WOS:000287010300009 PM 20817056 ER PT J AU Wright, ME Abdelzaher, AM Solo-Gabriele, HM Elmir, S Fleming, LE AF Wright, M. E. Abdelzaher, A. M. Solo-Gabriele, H. M. Elmir, S. Fleming, L. E. TI The inter-tidal zone is the pathway of input of enterococci to a subtropical recreational marine beach SO WATER SCIENCE AND TECHNOLOGY LA English DT Article DE enterococci; inter-tidal zone; marine beach; recreational beach; water quality indicators ID FECAL INDICATOR BACTERIA; ESCHERICHIA-COLI; WATER-QUALITY; LAKE-MICHIGAN; SAND; ENVIRONMENT; SEDIMENTS; POPULATIONS; PERSISTENCE; CALIFORNIA AB Efforts were made to evaluate the source of enterococci levels at a recreational beach. Four monitoring efforts were implemented which included tidal studies, hourly sampling, runoff sampling, and spatially intensive sediment sampling. Spatially intensive sediment sampling indicated that enterococci concentrations consistently decreased away from the inter-tidal zone, both seaward and landward. During dry conditions, the highest concentrations in the water were observed during high tide (71 +/- 48 CFU/100 mL) and lower concentrations were observed during low tide (4 +/- 3 CFU/100 mL). Runoff was characterised by very high levels (11,700 CFU/100 mL). Results from these monitoring efforts collectively showed that the source of enterococci to the study beach is geographically located within the inter-tidal zone. Wash-in from the inter-tidal zone through tidal action and runoff plays a major role in controlling enterococci levels within the water column. Such results are significant in identifying the source and transport mechanisms of enterococci, which can subsequently be used as part of a modelling effort aimed at predicting enterococci levels at recreational beaches. C1 [Wright, M. E.; Abdelzaher, A. M.; Solo-Gabriele, H. M.; Elmir, S.; Fleming, L. E.] Univ Miami, NSF, NIEHS, Oceans & Human Hlth Ctr,Rosenstiel Sch Marine & A, Miami, FL 33149 USA. [Wright, M. E.; Abdelzaher, A. M.; Solo-Gabriele, H. M.; Elmir, S.] Univ Miami, Dept Civil Architectural & Environm Engn, Coral Gables, FL 33124 USA. [Elmir, S.] Miami Dade Cty Hlth Dept, Miami, FL 33056 USA. [Fleming, L. E.] Univ Miami, Miller Sch Med, Dept Epidemiol & Publ Hlth, Miami, FL 33136 USA. RP Solo-Gabriele, HM (reprint author), Univ Miami, NSF, NIEHS, Oceans & Human Hlth Ctr,Rosenstiel Sch Marine & A, 4600 Rickenbacker Causeway,EG 211 Key Biscayne, Miami, FL 33149 USA. EM hmsolo@miami.edu FU NSF-NIEHS [NSF OCE0432368/0911373]; NIEHS [P50 ES12736-01]; NSF-REU [OCE 0432368] FX This work was funded by NSF-NIEHS Oceans.and Human Health Program (NSF OCE0432368/0911373 and NIEHS P50 ES12736-01) and the NSF-REU Program (OCE 0432368). We would like to thank all the students, scientists and professionals who assisted with sample collection. NR 26 TC 27 Z9 27 U1 3 U2 14 PU IWA PUBLISHING PI LONDON PA ALLIANCE HOUSE, 12 CAXTON ST, LONDON SW1H0QS, ENGLAND SN 0273-1223 J9 WATER SCI TECHNOL JI Water Sci. Technol. PY 2011 VL 63 IS 3 BP 542 EP 549 DI 10.2166/wst.2011.255 PG 8 WC Engineering, Environmental; Environmental Sciences; Water Resources SC Engineering; Environmental Sciences & Ecology; Water Resources GA 719DY UT WOS:000287181200023 PM 21278478 ER PT S AU Izumi, C Bird, J Schachinger, T Oliver, D Iwasa, KH AF Izumi, Chisako Bird, Jonathan Schaechinger, Torsten Oliver, Dominik Iwasa, Kuni H. BE Shera, CA Olson, ES TI The Evolution of Prestin: Examination with Membrane Thickness Sensitivity SO WHAT FIRE IS IN MINE EARS: PROGRESS IN AUDITORY BIOMECHANICS: PROCEEDINGS OF THE 11TH INTERNATIONAL MECHANICS OF HEARING WORKSHOP SE AIP Conference Proceedings LA English DT Proceedings Paper CT 11th International Workshop on the Mechanics of Hearing CY JUL 16-22, 2011 CL Williams Coll, Williamstown, MA HO Williams Coll DE evolution; membrane thickness; hydrophobic mismatch ID PROTEIN AB Prestin (SLC26A5) is a membrane protein that is essential for electromotility of outer hair cells and, in turn, for the cochlear amplifier. This function is mammalian innovation and prestin orthologs in non-mammalian hair cells function as anion exchangers rather than a motile element. Taking advantage of this evolutionary change, we found that the sensitivity of prestin orthologs to membrane thickness is inversely related to their effectiveness for the motile function. In addition, a chimera between zebrafish prestin and rat prestin, which shows motile functionality, has membrane thickness sensitivity lower than any prestin ortholog we have examined, confirming the relationship. C1 [Izumi, Chisako; Bird, Jonathan; Iwasa, Kuni H.] NIDCD, NIH, Bethesda, MD 20892 USA. [Izumi, Chisako] Hamamatsu Med Univ, Dept Otolaryngol, Hamamatsu, Shizuoka, Japan. [Schaechinger, Torsten] Univ Freiburg, Dept Phys, Freiburg, Germany. [Oliver, Dominik] Univ Marburg, Dept Physiol, Marburg, Germany. RP Izumi, C (reprint author), NIDCD, NIH, Bethesda, MD 20892 USA. OI Iwasa, Kuni/0000-0002-9397-7704 NR 4 TC 0 Z9 0 U1 0 U2 0 PU AMER INST PHYSICS PI MELVILLE PA 2 HUNTINGTON QUADRANGLE, STE 1NO1, MELVILLE, NY 11747-4501 USA SN 0094-243X BN 978-0-7354-0975-0 J9 AIP CONF PROC PY 2011 VL 1403 DI 10.1063/1.3658079 PG 2 WC Audiology & Speech-Language Pathology; Physics, Applied SC Audiology & Speech-Language Pathology; Physics GA BZL60 UT WOS:000301945200028 ER PT J AU Barbey, AK Grafman, J AF Barbey, Aron K. Grafman, Jordan TI An integrative cognitive neuroscience theory of social reasoning and moral judgment SO WILEY INTERDISCIPLINARY REVIEWS-COGNITIVE SCIENCE LA English DT Article ID MEDIAL PREFRONTAL CORTEX; WASON SELECTION TASK; NEURAL BASIS; INDIVIDUAL-DIFFERENCES; EVENT KNOWLEDGE; EXCHANGE; DAMAGE; FMRI; PERSPECTIVE; EVOLUTION AB Cognitive neuroscience has made considerable progress in understanding the involvement of the prefrontal cortex (PFC) in social cognition and moral judgment. Accumulating evidence suggests that representations within the lateral PFC enable people to orchestrate their thoughts and actions in concert with their intentions to support goal-directed social behavior. Despite the pivotal role of this region in guiding social interactions, remarkably little is known about the functional organization and forms of social knowledge mediated by the lateral PFC. Here, we review recent theoretical developments in evolutionary psychology and emerging evidence from the social and decision neuroscience literatures demonstrating the importance of the lateral PFC for orchestrating behavior on the basis of evolutionarily adaptive social norms for obligatory, prohibited, and permissible courses of action. (C) 2010 John Wiley& Sons, Ltd. WIREs Cogn Sci 2011 2 55-67 DOI: 10.1002/wcs.84 C1 [Barbey, Aron K.; Grafman, Jordan] NINDS, Cognit Neurosci Sect, NIH, Bethesda, MD 20892 USA. [Barbey, Aron K.] Georgetown Univ, Dept Psychol, Washington, DC 20057 USA. RP Grafman, J (reprint author), NINDS, Cognit Neurosci Sect, NIH, Bldg 36,Rm 4D04, Bethesda, MD 20892 USA. EM grafmanj@ninds.nih.gov RI Barbey, Aron/L-7312-2015; OI Barbey, Aron/0000-0002-6092-0912; Grafman, Jordan H./0000-0001-8645-4457 NR 106 TC 3 Z9 3 U1 2 U2 22 PU WILEY PERIODICALS, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN STREET, MALDEN, MA 02148-529 USA SN 1939-5078 J9 WIRES COGN SCI JI Wiley Interdiscip. Rev.-Cogn. Sci. PD JAN-FEB PY 2011 VL 2 IS 1 BP 55 EP 67 DI 10.1002/wcs.84 PG 13 WC Psychology, Experimental SC Psychology GA 863OL UT WOS:000298174800006 PM 26301913 ER PT J AU Tandon, P Nordstrom, RJ AF Tandon, Pushpa Nordstrom, Robert J. TI Next-generation imaging development for nanoparticle biodistribution measurements SO WILEY INTERDISCIPLINARY REVIEWS-NANOMEDICINE AND NANOBIOTECHNOLOGY LA English DT Review ID MAGNETIC-RESONANCE; CONTRAST AGENT; END-POINT; FLUORESCENCE; MELANOMA; TRIALS; MRI AB As nanotechnologies move closer to use in humans, quantitative imaging methods will play a vital role in answering questions of biodistribution. Accurate knowledge of the location and quantity of in vivo nanoconstructs and carriers is a challenging task, and newmethods of quantitative imaging at appropriate resolutions are being developed and tested. Sustaining simultaneous advancement in both imaging development and nanotechnology research requires multidisciplinary research teams conducting experiments with interconnected goals. On an even greater scale, networks of multidisciplinary teams focused on similar issues of imaging and probe development offer opportunities for leveraging resources, as well as providing a forum for sharing ideas and creating consensus on solutions to common challenges. The Network for Translational Research ( NTR): Optical Imaging in Multimodal Platforms from the National Cancer Institute is just such a network. Four multidisciplinary centers are accepting the challenges of developing and optimizing multimodal imaging hardware and software along with imaging probe development. These efforts are similar to the efforts that will be required for future studies of in vivo nanoparticle biodistribution. In addition to technology development and optimization, the network is organized to confront the challenges of validation of the imaging hardware and associated imaging agents, similar to the methods needed for validating nanomedicine. (C) 2010 John Wiley & Sons, Inc. WIREs Nanomed Nanobiotechnol 2011 3 5-10 DOI: 10.1002/wnan.117 C1 [Tandon, Pushpa; Nordstrom, Robert J.] NCI, NIH, Canc Imaging Program, Bethesda, MD 20892 USA. RP Tandon, P (reprint author), NCI, NIH, Canc Imaging Program, Bethesda, MD 20892 USA. EM tandonp@mail.nih.gov NR 19 TC 5 Z9 5 U1 1 U2 2 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1939-5116 EI 1939-0041 J9 WIRES NANOMED NANOBI JI Wiley Interdiscip. Rev.-Nanomed. Nanobiotechnol. PD JAN-FEB PY 2011 VL 3 IS 1 BP 5 EP 10 DI 10.1002/wnan.117 PG 6 WC Nanoscience & Nanotechnology; Medicine, Research & Experimental SC Science & Technology - Other Topics; Research & Experimental Medicine GA 701BQ UT WOS:000285789700002 PM 20842710 ER PT S AU Kovalchuk, I Nasibulina, A Reed, BM AF Kovalchuk, I. Nasibulina, A. Reed, B. M. BE Hummer, KE TI In Vitro Cold-Storage Duration of Cherry Shoots Is Affected by Carbon Source and Nitrogen Concentration SO XXVIII INTERNATIONAL HORTICULTURAL CONGRESS ON SCIENCE AND HORTICULTURE FOR PEOPLE (IHC2010): III INTERNATIONAL SYMPOSIUM ON PLANT GENETIC RESOURCES SE Acta Horticulturae LA English DT Proceedings Paper CT 28th International Horticultural Congress on Science and Horticulture for People/3rd International Symposium on Plant Genetic Resources CY AUG 22-27, 2010 CL Lisbon, PORTUGAL DE germplasm storage; in vitro storage; micropropagation; Prunus ID GERMPLASM; CULTURES; SURVIVAL; INVITRO; GROWTH AB In vitro cold storage of fruit crop germplasm is useful for preservation of heritage or commercial cultivars. Shoot cultures of sour cherry (Prunus cerasus L.) cultivars 'Dolgozdannaya', 'Moya Radost' and 'Zukovskaya', were cold stored at 4 degrees C in either five-section tissue-culture bags or in 150-ml glass jars. Carbon sources (3% sucrose, 2 or 3% mannitol, or 2% sucrose + 2% mannitol) were tested in Murashige and Skoog (MS) medium with or without plant growth regulators (PGRs). Nitrate nitrogen at 100, 50 or 25% of the normal MS concentration was also tested. In some treatments, shoot cultures of the three cherry cultivars stored at 4 degrees C remained viable for over 30 months. A significant variation in the storage duration and significant interactions of the cultivar, treatment, and container were observed. Sucrose was the best carbon source for all three genotypes and allowed storage for more than 30 months. Shoots stored on 2 or 3% mannitol survived only 6 to 12 months while the combination of 2% mannitol and 2% sucrose extended storage to 30 months. The addition of abscisic acid to 3% sucrose MS medium significantly decreased storage duration. 57 accessions of sour cherry germplasm were stored in tissue culture bags on 3% sucrose MS medium without PGRs and remained in good condition for 13 to 30 months. Currently, 68 P. cerasus germplasm accessions of the Kazakhstan National Cherry Collection are stored in tissue-culture bags with MS medium, PGRs, and 3% sucrose. C1 [Kovalchuk, I.; Nasibulina, A.] Natl Biotechnol Ctr, Inst Plant Biol & Biotechnol, Timiryazev Str 45, Alma Ata 050040, Kazakhstan. [Reed, B. M.] United States Dept Agr, Natl Clonal Germplasm Repository, Agr Res Serv, Corvallis, OR 97333 USA. RP Kovalchuk, I (reprint author), Natl Biotechnol Ctr, Inst Plant Biol & Biotechnol, Timiryazev Str 45, Alma Ata 050040, Kazakhstan. EM kovalchuk_i_u@mail.ru; Barbara.Reed@ars.usda.gov OI Reed, Barbara/0000-0003-0079-8473 FU International Science and Technology Center [K428]; US Department of Agriculture; Agricultural Research Service CRIS [5358- 21000- 033D] FX This project was supported by funds from the International Science and Technology Center Grant K428 and the US Department of Agriculture, Agricultural Research Service CRIS project 5358- 21000- 033D. NR 18 TC 2 Z9 2 U1 1 U2 4 PU INT SOC HORTICULTURAL SCIENCE PI LEUVEN 1 PA PO BOX 500, 3001 LEUVEN 1, BELGIUM SN 0567-7572 BN 978-90-66055-54-4 J9 ACTA HORTIC PY 2011 VL 918 BP 167 EP 175 PG 9 WC Horticulture SC Agriculture GA BDH95 UT WOS:000313331500020 ER PT J AU Boekhout, T Fonseca, A Sampaio, JP Bandoni, RJ Fell, JW Kwon-Chung, KJ AF Boekhout, Teun Fonseca, Alvaro Sampaio, Jose Paulo Bandoni, Robert J. Fell, Jack W. Kwon-Chung, Kyung J. BE Kurtzman, CP Fell, JW Boekhout, T TI Discussion of Teleomorphic and Anamorphic Basidiomycetous Yeasts SO YEASTS: A TAXONOMIC STUDY, VOLS 1-3, 5TH EDITION LA English DT Article; Book Chapter C1 [Boekhout, Teun] CBS KNAW Fungal Biodivers Ctr, NL-3584 CT Utrecht, Netherlands. [Bandoni, Robert J.] Univ British Columbia, Dept Bot, Vancouver, BC V6T 1Z4, Canada. [Fell, Jack W.] Univ Miami, Rosenstiel Sch Marine & Atmospher Sci, Key Biscayne, FL 33149 USA. [Fonseca, Alvaro; Sampaio, Jose Paulo] Univ Nova Lisboa, Ctr Recursos Microbiol CREM, Dept Ciencias Vida, Fac Ciencias & Tecnol, P-2829516 Caparica, Portugal. [Kwon-Chung, Kyung J.] NIAID, Mol Microbiol Sect, Lab Clin Infect Dis, NIH, Bethesda, MD 20892 USA. RP Boekhout, T (reprint author), CBS KNAW Fungal Biodivers Ctr, Uppsalalaan 8, NL-3584 CT Utrecht, Netherlands. RI Fonseca, Alvaro/C-5544-2011; OI Fonseca, Alvaro/0000-0001-9785-9433; Sampaio, Jose/0000-0001-8145-5274 NR 0 TC 32 Z9 33 U1 0 U2 3 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA SARA BURGERHARTSTRAAT 25, PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS BN 978-0-123-84868-0 PY 2011 BP 1339 EP 1372 DI 10.1016/B978-0-444-52149-1.00100-2 PG 34 WC Mycology SC Mycology GA BCV60 UT WOS:000311576700101 ER PT J AU Kwon-Chung, KJ AF Kwon-Chung, Kyung J. BE Kurtzman, CP Fell, JW Boekhout, T TI Chionosphaera Cox (1976) SO YEASTS: A TAXONOMIC STUDY, VOLS 1-3, 5TH EDITION LA English DT Article; Book Chapter C1 NIAID, Mol Microbiol Sect, Lab Clin Infect Dis, NIH, Bethesda, MD 20892 USA. RP Kwon-Chung, KJ (reprint author), NIAID, Mol Microbiol Sect, Lab Clin Infect Dis, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA. NR 0 TC 1 Z9 1 U1 0 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA SARA BURGERHARTSTRAAT 25, PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS BN 978-0-123-84868-0 PY 2011 BP 1395 EP 1401 DI 10.1016/B978-0-444-52149-1.00106-3 PG 7 WC Mycology SC Mycology GA BCV60 UT WOS:000311576700107 ER PT J AU Kwon-Chung, KJ AF Kwon-Chung, Kyung J. BE Kurtzman, CP Fell, JW Boekhout, T TI Filobasidiella Kwon-Chung (1975) SO YEASTS: A TAXONOMIC STUDY, VOLS 1-3, 5TH EDITION LA English DT Article; Book Chapter C1 NIAID, Mol Microbiol Sect, Lab Clin Infect Dis, NIH, Bethesda, MD 20892 USA. RP Kwon-Chung, KJ (reprint author), NIAID, Mol Microbiol Sect, Lab Clin Infect Dis, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA. NR 0 TC 5 Z9 5 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA SARA BURGERHARTSTRAAT 25, PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS BN 978-0-123-84868-0 PY 2011 BP 1443 EP 1455 DI 10.1016/B978-0-444-52149-1.00114-2 PG 13 WC Mycology SC Mycology GA BCV60 UT WOS:000311576700115 ER PT J AU Kwon-Chung, KJ AF Kwon-Chung, Kyung J. BE Kurtzman, CP Fell, JW Boekhout, T TI Filobasidium Olive (1968) SO YEASTS: A TAXONOMIC STUDY, VOLS 1-3, 5TH EDITION LA English DT Article; Book Chapter C1 NIAID, Mol Microbiol Sect, Lab Clin Infect Dis, NIH, Bethesda, MD 20892 USA. RP Kwon-Chung, KJ (reprint author), NIAID, Mol Microbiol Sect, Lab Clin Infect Dis, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA. NR 0 TC 3 Z9 3 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA SARA BURGERHARTSTRAAT 25, PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS BN 978-0-123-84868-0 PY 2011 BP 1457 EP 1465 DI 10.1016/B978-0-444-52149-1.00115-4 PG 9 WC Mycology SC Mycology GA BCV60 UT WOS:000311576700116 ER PT S AU Butler, MG Gore, AV Weinstein, BM AF Butler, Matthew G. Gore, Aniket V. Weinstein, Brant M. BE Detrich, HW Westerfield, M Zon, LI TI Zebrafish as a Model for Hemorrhagic Stroke SO ZEBRAFISH: DISEASE MODELS AND CHEMICAL SCREENS, 3RD EDITION SE Methods in Cell Biology LA English DT Review; Book Chapter ID CEREBRAL CAVERNOUS MALFORMATIONS; VASCULAR ENDOTHELIAL CADHERIN; BLOOD-BRAIN-BARRIER; ZINC-FINGER PROTEIN; IN-FRAME DELETION; VE-CADHERIN; CELL-JUNCTIONS; TIGHT JUNCTION; TYROSINE PHOSPHORYLATION; MOLECULAR-ORGANIZATION AB Blood vessels perform the fundamental role of providing conduits for the circulation of oxygen and nutrients and the removal of waste products throughout the body. Disruption of tissue perfusion by ischemia or hemorrhage of blood vessels has a range of devastating consequences including stroke. Stroke is a complex trait that includes both genetic and environmental risk factors. The zebrafish is an attractive model for the study of hemorrhagic stroke due to the conservation of the molecular mechanisms of blood vascular development among vertebrates and the experimental advantages that can be applied to zebrafish embryos and larva. This chapter will focus on the maintenance of vascular integrity and some of the seminal experimentation carried out in the zebrafish. C1 [Butler, Matthew G.; Gore, Aniket V.; Weinstein, Brant M.] Natl Inst Child Hlth & Dev, Program Genom Differentiat, NIH, Bethesda, MD USA. RP Butler, MG (reprint author), Natl Inst Child Hlth & Dev, Program Genom Differentiat, NIH, Bethesda, MD USA. NR 105 TC 4 Z9 4 U1 1 U2 5 PU ELSEVIER ACADEMIC PRESS INC PI SAN DIEGO PA 525 B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 USA SN 0091-679X BN 978-0-12-381320-6 J9 METHOD CELL BIOL JI Methods Cell Biol. PY 2011 VL 105 BP 137 EP 161 DI 10.1016/B978-0-12-381320-6.00006-0 PG 25 WC Cell Biology; Medicine, Research & Experimental SC Cell Biology; Research & Experimental Medicine GA BXA72 UT WOS:000295550300006 PM 21951529 ER PT S AU Amsterdam, A Varshney, GK Burgess, SM AF Amsterdam, Adam Varshney, Gaurav Kumar Burgess, Shawn Michael BE Detrich, HW Westerfield, M Zon, LI TI Retroviral-mediated Insertional Mutagenesis in Zebrafish SO ZEBRAFISH: GENETICS, GENOMICS AND INFORMATICS, 3RD EDITION SE Methods in Cell Biology LA English DT Review; Book Chapter ID SLEEPING-BEAUTY TRANSPOSON; GERM-LINE TRANSMISSION; VESICULAR STOMATITIS-VIRUS; DROSOPHILA GENOME; DANIO-RERIO; PROVIRAL INSERTIONS; TUMOR-SUPPRESSOR; FACTOR-I; GENE; INTEGRATION AB Since the initial publication of this chapter in 2004, additional methodologies have been developed which could improve and/or complement the original retroviral-mediated insertional mutagenesis. Retroviral vectors have also been shown to be useful for goals other than mutagenesis. In addition, retroviral-mediated insertional mutagenesis has been applied to zebrafish for use in reverse genetics as well as forward screening. Finally, the insertional mutant collection described herein has been screened by a number of labs to find a host of mutants (with genes already identified) with developmental and/or growth defects affecting the eye, liver, skin, craniofacial skeleton, kidney, myeloid cells, hematopoietic stem cells, and axon pathfinding, as well as mutants with defects in the cell cycle or DNA damage response, altered aging properties, and modulated cardiac repolarization. The major complementary approaches and new uses of this technique include: Pseudotyped retroviruses have been used to deliver enhancer trap vectors, which allows selection of insertions in or near genes with particular expression patterns. Although the mutagenicity of these vectors has yet to be determined, they are useful purely because they generate a large number of transgenic lines with visible reporters (e.g., Green Fluorescent Protein GFP) expressed in interesting patterns and they provide information regarding gene regulation in the context of genomic organization. Gain-of-function vectors have been designed to allow for dominant genetic screens. Thus, genes whose overexpression results in phenotypes of interest can be efficiently identified. Retroviruses can be used to make a library of insertions in which hundreds of thousands of mapped insertions can be recovered from frozen sperm samples. Such libraries could serve as on-the-shelf reverse genetic resources, whereby one can obtain a mutation in nearly any gene by simply recovering an insertion in that gene from the frozen sperm, similar to the use of gene-trap insertions and genome-wide gene targeting in ES cells in the mouse. Transposons have been shown to be nearly as effective transgenesis vectors as retroviruses and thus may be used in similar screens - both for mutagenicity and gene traps and enhancer traps. It is possible that retroviruses and transposons could have different insertion site biases, making them important complementary technologies for genome-wide screening. C1 [Amsterdam, Adam] MIT, Koch Inst Integrat Canc Res, Cambridge, MA 02139 USA. [Varshney, Gaurav Kumar; Burgess, Shawn Michael] NHGRI, Bethesda, MD 20892 USA. RP Amsterdam, A (reprint author), MIT, Koch Inst Integrat Canc Res, 77 Massachusetts Ave, Cambridge, MA 02139 USA. RI Varshney, Gaurav/L-5261-2014; OI Burgess, Shawn/0000-0003-1147-0596; Varshney, Gaurav K./0000-0002-0429-1904 FU Intramural NIH HHS [ZIA HG000183-11] NR 63 TC 11 Z9 11 U1 0 U2 6 PU ELSEVIER ACADEMIC PRESS INC PI SAN DIEGO PA 525 B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 USA SN 0091-679X BN 978-0-12-374814-0 J9 METHOD CELL BIOL JI Methods Cell Biol. PY 2011 VL 104 SI 3 BP 59 EP 82 DI 10.1016/B978-0-12-374814-0.00004-5 PG 24 WC Cell Biology SC Cell Biology GA BXA74 UT WOS:000295551800004 PM 21924157 ER PT S AU Liang, J Renaud, G Burgess, SM AF Liang, Jin Renaud, Gabriel Burgess, Shawn M. BE Detrich, HW Westerfield, M Zon, LI TI Sequencing-based Expression Profiling in Zebrafish SO ZEBRAFISH: GENETICS, GENOMICS AND INFORMATICS, 3RD EDITION SE Methods in Cell Biology LA English DT Review; Book Chapter ID GENE-EXPRESSION; RNA-SEQ; SERIAL ANALYSIS; HUMAN GENOME; TRANSCRIPTOME; MICROARRAY; ACCURATE; REVEALS; TAGS AB Gene expression profiling is a powerful technique for studying biological processes, especially tissue/organ-specific ones, at the molecular level. With the rapid development of the next-generation sequencing techniques, high throughput sequencing-based expression profiling techniques have been more and more widely adopted in molecular biology studies. In this chapter, we described a protocol for applying one of the sequencing-based expression profiling techniques, Digital Gene Expression (DGE), for zebrafish research. The protocol provides guidelines for wet-bench experimental procedures as well as for bioinformatics data analyses. We also discuss potential issues/challenges with the use of DGE. C1 [Liang, Jin; Renaud, Gabriel; Burgess, Shawn M.] NHGRI, Bethesda, MD 20892 USA. RP Liang, J (reprint author), NHGRI, Bethesda, MD 20892 USA. OI Burgess, Shawn/0000-0003-1147-0596 FU Intramural NIH HHS [ZIA HG000183-11] NR 32 TC 0 Z9 0 U1 1 U2 5 PU ELSEVIER ACADEMIC PRESS INC PI SAN DIEGO PA 525 B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 USA SN 0091-679X BN 978-0-12-374814-0 J9 METHOD CELL BIOL JI Methods Cell Biol. PY 2011 VL 104 SI 3 BP 379 EP 399 DI 10.1016/B978-0-12-374814-0.00021-5 PG 21 WC Cell Biology SC Cell Biology GA BXA74 UT WOS:000295551800021 PM 21924174 ER PT S AU Fero, K Yokogawa, T Burgess, HA AF Fero, Kandice Yokogawa, Tohei Burgess, Harold A. BE Kalueff, AV Cachat, JM TI The Behavioral Repertoire of Larval Zebrafish SO ZEBRAFISH MODELS IN NEUROBEHAVIORAL RESEARCH SE Neuromethods LA English DT Article; Book Chapter DE Developing zebrafish; larvae; acoustic/vibrational stimuli; vestibular stimuli; lateral line stimuli; visual stimuli; chemical stimuli; locomotion; sensory cues; environmental adaptation; stereotypic behavior; neuroanatomy; neuronal pathways; motor control; sensory processing ID PONTINE RETICULAR-FORMATION; DANIO-RERIO; LATERAL-LINE; BRACHYDANIO-RERIO; STARTLE RESPONSE; OPTOKINETIC NYSTAGMUS; PREY CAPTURE; CIRCADIAN RHYTHMICITY; PREPULSE INHIBITION; EMBRYONIC ZEBRAFISH AB Shortly after larval zebrafish become free swimming their behavior is modulated by both autochthonous signals and external stimuli Larvae show rapid responses to a range of sensory cues but are also capable of executing extended behavioral programs in response to changes in the environment At this early stage, larvae have a small repertoire of discrete stereotyped movements which are deployed in different contexts to generate appropriate behavior We outline the range of behaviors defined in zebrafish larva to date and discuss insights into neural function revealed by behavioral assays A growing body of work demonstrates that tractability of behavior and neural connectivity in larval zebrafish facilitate the analysis of neural pathways underlying vertebrate motor control and sensory processing C1 [Fero, Kandice; Yokogawa, Tohei; Burgess, Harold A.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Mol Genet Lab, NIH, Bethesda, MD USA. RP Fero, K (reprint author), Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Mol Genet Lab, NIH, Bethesda, MD USA. RI Burgess, Harold/B-8474-2015 OI Burgess, Harold/0000-0003-1966-7801 NR 204 TC 27 Z9 28 U1 0 U2 16 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DR, STE 208, TOTOWA, NJ 07512-1165 USA SN 0893-2336 BN 978-1-60761-921-5 J9 NEUROMETHODS JI Neuromethods PY 2011 VL 52 BP 249 EP 291 DI 10.1007/978.1.60761.922.2_12 D2 10.1007/978-1-60761-922-2 PG 43 WC Cell Biology; Neurosciences SC Cell Biology; Neurosciences & Neurology GA BSA48 UT WOS:000284030800012 ER PT J AU Brady, RO AF Brady, Roscoe O. TI Benefits from Unearthing "a Biochemical Rosetta Stone" SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Editorial Material ID INHERITED ENZYME DEFICIENCY; NIEMANN-PICK DISEASE; GLUCOCEREBROSIDE-CLEAVING ENZYME; IN-UTERO DIAGNOSIS; GAUCHERS-DISEASE; REPLACEMENT THERAPY; FABRYS-DISEASE; PURIFIED GLUCOCEREBROSIDASE; FATTY ACIDS; METABOLISM C1 NINDS, NIH, Bethesda, MD 20892 USA. RP Brady, RO (reprint author), NINDS, NIH, Bethesda, MD 20892 USA. EM bradyr@ninds.nih.gov NR 46 TC 7 Z9 7 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 J9 J BIOL CHEM JI J. Biol. Chem. PD DEC 31 PY 2010 VL 285 IS 53 BP 41216 EP 41221 DI 10.1074/jbc.X110.197954 PG 6 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 698VV UT WOS:000285622600007 PM 21030589 ER PT J AU Walseng, E Furuta, K Goldszmid, RS Weih, KA Sher, A Roche, PA AF Walseng, Even Furuta, Kazuyuki Goldszmid, Romina S. Weih, Karis A. Sher, Alan Roche, Paul A. TI Dendritic Cell Activation Prevents MHC Class II Ubiquitination and Promotes MHC Class II Survival Regardless of the Activation Stimulus SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID TOXOPLASMA-GONDII; PLASMA-MEMBRANE; COMPLEXES; SURFACE; EXPRESSION; MATURATION; INFECTION; TRANSPORT; PARASITES; FUSION AB The expression of MHC class II (MHC-II) on the surface of antigen-presenting cells, such as dendritic cells (DCs), is tightly regulated during cellular activation. Many cells, including DCs, are activated following stimulation of innate Toll-like receptors (TLRs) by products of microorganisms. In the resting (immature) state, MHC-II is ubiquitinated in immature DCs and is rapidly degraded; however, after activation of these cells with MyD88-dependent TLR ligands, MHC-II ubiquitination is blocked, and MHC-II survival is prolonged. We now show that DC activation using MyD88-dependent TLR ligands, MyD88-independent TLR ligands, and even infection with the intracellular parasite Toxoplasma gondii leads to identical changes in MHC-II expression, ubiquitination, and surface stability, revealing a conserved role for enhanced MHC-II stability after DC activation by different stimuli. C1 [Walseng, Even; Furuta, Kazuyuki; Weih, Karis A.; Roche, Paul A.] NCI, Expt Immunol Branch, NIH, Bethesda, MD 20892 USA. [Goldszmid, Romina S.; Sher, Alan] NIAID, Parasit Dis Lab, NIH, Bethesda, MD 20892 USA. [Goldszmid, Romina S.] NCI, Expt Immunol Lab, Canc & Inflammat Program, Ctr Canc Res,NIH, Frederick, MD 21702 USA. RP Roche, PA (reprint author), NCI, Expt Immunol Branch, NIH, Bldg 10,Rm 4B36, Bethesda, MD 20892 USA. EM paul.roche@nih.gov FU National Institutes of Health of NCI and NIAID FX This work was supported, in whole or in part, by the National Institutes of Health Intramural Research Programs of NCI and NIAID. NR 23 TC 23 Z9 23 U1 0 U2 1 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD DEC 31 PY 2010 VL 285 IS 53 BP 41749 EP 41754 DI 10.1074/jbc.M110.157586 PG 6 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 698VV UT WOS:000285622600062 PM 21047782 ER PT J AU Legiewicz, M Zolotukhin, AS Pilkington, GR Purzycka, KJ Mitchell, M Uranishi, H Bear, J Pavlakis, GN Le Grice, SFJ Felber, BK AF Legiewicz, Michal Zolotukhin, Andrei S. Pilkington, Guy R. Purzycka, Katarzyna J. Mitchell, Michelle Uranishi, Hiroaki Bear, Jenifer Pavlakis, George N. Le Grice, Stuart F. J. Felber, Barbara K. TI The RNA Transport Element of the Murine musD Retrotransposon Requires Long-range Intramolecular Interactions for Function SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID IMMUNODEFICIENCY-VIRUS TYPE-1; KISSING-LOOP INTERACTION; SELECTIVE 2'-HYDROXYL ACYLATION; SINGLE NUCLEOTIDE RESOLUTION; PRIMER EXTENSION SHAPE; REV RESPONSE ELEMENT; VIRAL MESSENGER-RNA; SECONDARY STRUCTURE; NUCLEAR EXPORT; MUTATIONAL ANALYSIS AB Retrovirus replication requires specialized transport mechanisms to export genomic mRNA from the nucleus to the cytoplasm of the infected cell. This regulation is mediated by a combination of viral and/or cellular factors that interact with cis-acting RNA export elements linking the viral RNA to the cellular CRM1 or NXF1 nuclear export pathways. Endogenous type D murine LTR retrotransposons (musD) were reported to contain an RNA export element located upstream of the 3'-LTR. Although functionally equivalent, the musD export element, termed the musD transport element, is distinct from the other retroviral RNA export elements, such as the constitutive transport element of simian/Mason-Pfizer monkey retroviruses and the RNA transport element found in rodent intracisternal A-particle LTR retrotransposons. We demonstrate here that the minimal RNA transport element (musD transport element) of musD comprises multiple secondary structure elements that presumably serve as recognition signals for the cellular export machinery. We identified two classes of tertiary interactions, namely kissing loops and a pseudoknot. This work constitutes the first example of an RNA transport element requiring such structural motifs to mediate nuclear export. C1 [Le Grice, Stuart F. J.] NCI, RT Biochem Sect, HIV Drug Resistance Program, Vaccine Branch,Ctr Canc Res,NIH, Frederick, MD 21702 USA. [Zolotukhin, Andrei S.; Pilkington, Guy R.; Bear, Jenifer; Felber, Barbara K.] NCI, Human Retrovirus Pathogenesis Sect, NIH, Frederick, MD 21702 USA. [Uranishi, Hiroaki; Pavlakis, George N.] NCI, Human Retrovirus Sect, Vaccine Branch, Ctr Canc Res,NIH, Frederick, MD 21702 USA. RP Le Grice, SFJ (reprint author), NCI, RT Biochem Sect, HIV Drug Resistance Program, Vaccine Branch,Ctr Canc Res,NIH, POB B,Bldg 535,Rm 206, Frederick, MD 21702 USA. EM legrices@mail.nih.gov; felberb@mail.nih.gov FU National Institutes of Health of the NCI Center for Cancer Research FX This work was supported, in whole or in part, by the National Institutes of Health Intramural Research Program of the NCI Center for Cancer Research. NR 49 TC 15 Z9 15 U1 1 U2 3 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD DEC 31 PY 2010 VL 285 IS 53 BP 42097 EP 42104 DI 10.1074/jbc.M110.182840 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 698VV UT WOS:000285622600094 PM 20978285 ER PT J AU Horvath, B Lenzser, G Benyo, B Nemeth, T Benko, R Iring, A Herman, P Komjati, K Lacza, Z Sandor, P Benyo, Z AF Horvath, Bela Lenzser, Gabor Benyo, Balazs Nemeth, Tamas Benko, Rita Iring, Andras Herman, Peter Komjati, Katalin Lacza, Zsombor Sandor, Peter Benyo, Zoltan TI Hypersensitivity to Thromboxane Receptor Mediated Cerebral Vasomotion and CBF Oscillations during Acute NO-Deficiency in Rats SO PLOS ONE LA English DT Article ID DEPENDENT PROTEIN-KINASE; OXIDE SYNTHASE BLOCKADE; VASCULAR SMOOTH-MUSCLE; NITRIC-OXIDE; BLOOD-FLOW; MYOSIN PHOSPHATASE; LASER-DOPPLER; SUBARACHNOID HEMORRHAGE; PROSTAGLANDIN I-2; HYPERTENSIVE RATS AB Background: Low frequency (4-12 cpm) spontaneous fluctuations of the cerebrovascular tone (vasomotion) and oscillations of the cerebral blood flow (CBF) have been reported in diseases associated with endothelial dysfunction. Since endothelium-derived nitric oxide (NO) suppresses constitutively the release and vascular effects of thromboxane A(2) (TXA(2)), NO-deficiency is often associated with activation of thromboxane receptors (TP). In the present study we hypothesized that in the absence of NO, overactivation of the TP-receptor mediated cerebrovascular signaling pathway contributes to the development of vasomotion and CBF oscillations. Methodology/Principal Findings: Effects of pharmacological modulation of TP-receptor activation and its downstream signaling pathway have been investigated on CBF oscillations (measured by laser-Doppler flowmetry in anesthetized rats) and vasomotion (measured by isometric tension recording in isolated rat middle cerebral arteries, MCAs) both under physiological conditions and after acute inhibition of NO synthesis. Administration of the TP-receptor agonist U-46619 (1 mu g/kg iv.) to control animals failed to induce any changes of the systemic or cerebral circulatory parameters. Inhibition of the NO synthesis by nitro-L-arginine methyl esther (L-NAME, 100 mg/kg iv.) resulted in increased mean arterial blood pressure and a decreased CBF accompanied by appearance of CBF-oscillations with a dominant frequency of 148+/-2 mHz. U-46619 significantly augmented the CBF-oscillations induced by L-NAME while inhibition of endogenous TXA(2) synthesis by ozagrel (10 mg/kg iv.) attenuated it. In isolated MCAs U-46619 in a concentration of 100 nM, which induced weak and stable contraction under physiological conditions, evoked sustained vasomotion in the absence of NO, which effect could be completely reversed by inhibition of Rho-kinase by 10 mu M Y-27632. Conclusion/Significance: These results suggest that hypersensitivity of the TP-receptor - Rho-kinase signaling pathway contributes to the development of low frequency cerebral vasomotion which may propagate to vasospasm in pathophysiological states associated with NO-deficiency. C1 [Horvath, Bela; Lenzser, Gabor; Nemeth, Tamas; Benko, Rita; Iring, Andras; Herman, Peter; Komjati, Katalin; Lacza, Zsombor; Sandor, Peter; Benyo, Zoltan] Semmelweis Univ, Inst Human Physiol & Clin Expt Res, Budapest, Hungary. [Horvath, Bela] NIAAA, NIH, Bethesda, MD USA. [Lenzser, Gabor] Univ Pecs, Dept Neurosurg, Pecs, Hungary. [Benyo, Balazs] Budapest Univ Technol & Econ, Dept Control Engn & Informat Technol, H-1117 Budapest, Hungary. [Herman, Peter] Yale Univ, Dept Diagnost Radiol, Magnet Resonance Res Ctr, New Haven, CT 06510 USA. RP Horvath, B (reprint author), Semmelweis Univ, Inst Human Physiol & Clin Expt Res, Budapest, Hungary. EM bela.horvath@nih.gov RI Iring, Andras/F-7092-2010; Horvath, Bela/A-7368-2009; Benyo, Balazs/H-6208-2012; OI Benyo, Balazs/0000-0003-2770-9127; Benyo, Zoltan/0000-0001-6015-0359 FU EFSD) European Foundation for the Study of Diabetes/Servier; Hungarian Scientific Research Fund (OTKA) [K 62375, K82066]; NKTH National Office for Research and Technology [OMFB-00770/2009, ALAP1-01298/2009]; ESZCSM Health Science Council (ETT) [427/2009]; Tarsadalmi Megujulas Operativ Program (TAMOP) [4.2.2-08/1/KMR-2008-004, 4.2.1/B-09/1/KMR-2010-000]; NKTH-OTKA-EU [MB08-A 80238] FX This study was supported by an (EFSD) European Foundation for the Study of Diabetes/Servier grant as well as by grants from the The Hungarian Scientific Research Fund (Hungarian abbreviation: OTKA) (K 62375, K82066), NKTH National Office for Research and Technology (OMFB-00770/2009, ALAP1-01298/2009), ESZCSM Health Science Council (ETT)(427/2009) and Tarsadalmi Megujulas Operativ Program (TAMOP) (4.2.2-08/1/KMR-2008-004, 4.2.1/B-09/1/KMR-2010-000). Dr. Horvath was supported by an NKTH-OTKA-EU Fellowship (MB08-A 80238). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 42 TC 6 Z9 7 U1 1 U2 9 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA SN 1932-6203 J9 PLOS ONE JI PLoS One PD DEC 31 PY 2010 VL 5 IS 12 AR e14477 DI 10.1371/journal.pone.0014477 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 701RA UT WOS:000285838900006 PM 21217826 ER PT J AU Sabir, N Riazuddin, SA Kaul, H Iqbal, F Nasir, IA Zafar, AU Qazi, ZA Butt, NH Khan, SN Husnain, T Hejtmancik, JF Riazuddin, S AF Sabir, Namerah Riazuddin, S. Amer Kaul, Haiba Iqbal, Farheena Nasir, Idrees A. Zafar, Ahmad U. Qazi, Zaheeruddin A. Butt, Nadeem H. Khan, Shaheen N. Husnain, Tayyab Hejtmancik, J. Fielding Riazuddin, Sheikh TI Mapping of a novel locus associated with autosomal recessive congenital cataract to chromosome 8p SO MOLECULAR VISION LA English DT Article ID PAKISTANI FAMILY; CHILDHOOD BLINDNESS; NONSENSE MUTATION; GENE; MAPS AB Purpose: To identify the disease locus for autosomal recessive congenital cataracts in a consanguineous Pakistani family. Methods: All affected individuals underwent a detailed ophthalmologic examination. Blood samples were collected and genomic DNA was extracted. A genome-wide scan was completed with fluorescently-labeled microsatellite markers on genomic DNA from affected and unaffected family members. Logarithms of odds (LOD) scores were calculated under a fully penetrant autosomal recessive model of inheritance. Results: Ophthalmic examination suggested that affected individuals have bilateral cataracts. Linkage analysis localized the critical interval to chromosome 8p with LOD scores of 3.19, and 3.08 at theta=0, obtained with markers D8S549 and D8S550, respectively. Haplotype analyses refined the critical interval to 37.92 cM (16.28 Mb) region, flanked by markers, D8S277 proximally and D8S1734 distally. Conclusions: Here, we report a new locus for autosomal recessive congenital cataract mapped to chromosome 8p in a consanguineous Pakistani family. C1 [Sabir, Namerah; Riazuddin, S. Amer; Kaul, Haiba; Iqbal, Farheena; Nasir, Idrees A.; Zafar, Ahmad U.; Khan, Shaheen N.; Husnain, Tayyab; Riazuddin, Sheikh] Univ Punjab, Natl Ctr Excellence Mol Biol, Lahore 53700, Pakistan. [Riazuddin, S. Amer] Johns Hopkins Univ, Sch Med, Wilmer Eye Inst, Baltimore, MD 21205 USA. [Butt, Nadeem H.; Riazuddin, Sheikh] Univ Hlth Sci, Allama Iqbal Med Coll, Lahore, Pakistan. [Qazi, Zaheeruddin A.] Layton Rahmatulla Benevolent Trust Hosp, Lahore, Pakistan. [Hejtmancik, J. Fielding] NEI, Ophthalm Genet & Visual Funct Branch, NIH, Bethesda, MD 20892 USA. RP Riazuddin, S (reprint author), Univ Punjab, Natl Ctr Excellence Mol Biol, 87 W Canal Bank Rd, Lahore 53700, Pakistan. EM riaz@aimrc.org RI Nasim Khan, Shaheen/F-2135-2015; Husnain, Tayyab/G-3805-2015 FU Higher Education Commission, Pakistan; Ministry of Science and Technology Islamabad, Pakistan; National Academy of Sciences; U.S. Department of State, Washington DC USA FX The authors are thankful to all the family members for their participation in this study. This study was supported, in part by Higher Education Commission and Ministry of Science and Technology Islamabad, Pakistan, and the National Academy of Sciences, and the U.S. Department of State, Washington DC USA (Note: All findings and conclusions are those of the authors and do not necessarily reflect the views of the National Academy of Sciences and the U. S. Department of State). NR 24 TC 5 Z9 5 U1 0 U2 0 PU MOLECULAR VISION PI ATLANTA PA C/O JEFF BOATRIGHT, LAB B, 5500 EMORY EYE CENTER, 1327 CLIFTON RD, N E, ATLANTA, GA 30322 USA SN 1090-0535 J9 MOL VIS JI Mol. Vis. PD DEC 30 PY 2010 VL 16 IS 312 BP 2911 EP 2915 PG 5 WC Biochemistry & Molecular Biology; Ophthalmology SC Biochemistry & Molecular Biology; Ophthalmology GA 707UN UT WOS:000286314100001 PM 21203409 ER PT J AU Grant, RM Lama, JR Anderson, PL McMahan, V Liu, AY Vargas, L Goicochea, P Casapia, M Guanira-Carranza, JV Ramirez-Cardich, ME Montoya-Herrera, O Fernandez, T Veloso, VG Buchbinder, SP Chariyalertsak, S Schechter, M Bekker, LG Mayer, KH Kallas, EG Amico, KR Mulligan, K Bushman, LR Hance, RJ Ganoza, C Defechereux, P Postle, B Wang, FR McConnell, JJ Zheng, JH Lee, J Rooney, JF Jaffe, HS Martinez, AI Burns, DN Glidden, DV AF Grant, Robert M. Lama, Javier R. Anderson, Peter L. McMahan, Vanessa Liu, Albert Y. Vargas, Lorena Goicochea, Pedro Casapia, Martin Guanira-Carranza, Juan Vicente Ramirez-Cardich, Maria E. Montoya-Herrera, Orlando Fernandez, Telmo Veloso, Valdilea G. Buchbinder, Susan P. Chariyalertsak, Suwat Schechter, Mauro Bekker, Linda-Gail Mayer, Kenneth H. Kallas, Esper Georges Amico, K. Rivet Mulligan, Kathleen Bushman, Lane R. Hance, Robert J. Ganoza, Carmela Defechereux, Patricia Postle, Brian Wang, Furong McConnell, J. Jeff Zheng, Jia-Hua Lee, Jeanny Rooney, James F. Jaffe, Howard S. Martinez, Ana I. Burns, David N. Glidden, David V. CA iPrEx Study Team TI Preexposure Chemoprophylaxis for HIV Prevention in Men Who Have Sex with Men. SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Article ID NONOCCUPATIONAL POSTEXPOSURE PROPHYLAXIS; MALE CIRCUMCISION; LIMITED KNOWLEDGE; HOMOSEXUAL-MEN; INFECTION; TRANSMISSION; RISK; TENOFOVIR; MACAQUES; TRIAL AB Background: Antiretroviral chemoprophylaxis before exposure is a promising approach for the prevention of human immunodeficiency virus (HIV) acquisition. Methods: We randomly assigned 2499 HIV-seronegative men or transgender women who have sex with men to receive a combination of two oral antiretroviral drugs, emtricitabine and tenofovir disoproxil fumarate (FTC-TDF), or placebo once daily. All subjects received HIV testing, risk-reduction counseling, condoms, and management of sexually transmitted infections. Results: The study subjects were followed for 3324 person-years (median, 1.2 years; maximum, 2.8 years). Of these subjects, 10 were found to have been infected with HIV at enrollment, and 100 became infected during follow-up (36 in the FTC-TDF group and 64 in the placebo group), indicating a 44% reduction in the incidence of HIV (95% confidence interval, 15 to 63; P=0.005). In the FTC-TDF group, the study drug was detected in 22 of 43 of seronegative subjects (51%) and in 3 of 34 HIV-infected subjects (9%) (P<0.001). Nausea was reported more frequently during the first 4 weeks in the FTC-TDF group than in the placebo group (P<0.001). The two groups had similar rates of serious adverse events (P=0.57). Conclusions: Oral FTC-TDF provided protection against the acquisition of HIV infection among the subjects. Detectable blood levels strongly correlated with the prophylactic effect. (Funded by the National Institutes of Health and the Bill and Melinda Gates Foundation; ClinicalTrials.gov number, NCT00458393.) N Engl J Med 2010;363:2587-99. C1 [Liu, Albert Y.; Buchbinder, Susan P.] San Francisco Dept Publ Hlth, HIV Res Sect, San Francisco, CA USA. [Lama, Javier R.; Vargas, Lorena] Invest Med Salud, Lima, Peru. [Lama, Javier R.; Guanira-Carranza, Juan Vicente; Ramirez-Cardich, Maria E.; Ganoza, Carmela] Asociac Civil Impacta Salud & Educ, Lima, Peru. [Casapia, Martin] Asociac Civil Selva Amazon, Iquitos, Peru. [Anderson, Peter L.; Bushman, Lane R.; Zheng, Jia-Hua] Univ Colorado, Denver, CO 80202 USA. [Montoya-Herrera, Orlando; Fernandez, Telmo] Fdn Ecuatoriana Equidad, Guayaquil, Ecuador. [Veloso, Valdilea G.] Fundacao Oswaldo Cruz, Inst Pesquisa Clin Evandro Chagas, Rio De Janeiro, Brazil. [Schechter, Mauro] Univ Fed Rio de Janeiro, Hosp Escola Sao Francisco de Assis, Projeto Praca Onze, Rio De Janeiro, Brazil. [Mayer, Kenneth H.] Brown Univ, Providence, RI 02912 USA. [Mayer, Kenneth H.] Fenway Hlth, Fenway Inst, Boston, MA USA. [Kallas, Esper Georges] Univ Sao Paulo, Sch Med, Div Clin Immunol & Allergy, Sao Paulo, Brazil. [Kallas, Esper Georges] Inst Invest Imunol, Sao Paulo, Brazil. [Chariyalertsak, Suwat] Chiang Mai Univ, Res Inst Hlth Sci, Chiang Mai 50000, Thailand. [Bekker, Linda-Gail] Univ Cape Town, Desmond Tutu HIV Ctr, ZA-7925 Cape Town, South Africa. [Bekker, Linda-Gail] Univ Cape Town, Dept Med, ZA-7925 Cape Town, South Africa. [Martinez, Ana I.; Burns, David N.] NIAID, Div Aids, NIH, Bethesda, MD 20892 USA. [Rooney, James F.; Jaffe, Howard S.] Gilead Sci Inc, Foster City, CA 94404 USA. [Postle, Brian] DF Net Res, Seattle, WA USA. [Amico, K. Rivet] Appl Hlth Res, Brighton, MI USA. [Amico, K. Rivet] Univ Connecticut, Ctr Hlth Intervent & Prevent, Storrs, CT USA. [Grant, Robert M.; McMahan, Vanessa; Goicochea, Pedro; Hance, Robert J.; Defechereux, Patricia; McConnell, J. Jeff; Lee, Jeanny] Univ Calif San Francisco, Gladstone Inst Virol & Immunol, San Francisco, CA 94158 USA. RP Grant, RM (reprint author), Univ Calif San Francisco, J David Gladstone Inst, 1650 Owens St, San Francisco, CA 94158 USA. EM robert.grant@ucsf.edu RI Kallas, Esper/C-9539-2012; Goncalves Veloso, Valdilea/J-6189-2012; Imunologia, Inct/I-2124-2013; OI Guanira, Juan/0000-0002-2746-3086 FU Division of Acquired Immunodeficiency Syndrome (DAIDS), National Institute of Allergy and Infectious Diseases, National Institutes of Health [UO1 AI64002]; Bill and Melinda Gates Foundation; DAIDS [UO1 AI84735, AI062333]; National Institutes of Health [UL1 RR024131]; Gilead; Merck; Bristol-Myers Squibb FX Supported by the Division of Acquired Immunodeficiency Syndrome (DAIDS), National Institute of Allergy and Infectious Diseases, National Institutes of Health, as a cooperative agreement (UO1 AI64002, to Dr. Grant) and by the Bill and Melinda Gates Foundation. Study drugs were donated by Gilead Sciences. The pharmacological studies were sponsored by a cooperative agreement with DAIDS (UO1 AI84735, to Dr. Anderson). Support for some specimen handling came from a grant from DAIDS (RO1 AI062333, to Dr. Grant) and by the J. David Gladstone Institutes. Some infrastructure support at the University of California at San Francisco was provided by a grant from the National Institutes of Health (UL1 RR024131).; Dr. Grant reports receiving support as an advisor to Siemens (the manufacturer of TruGene HIV-1 Genotyping Kit); Dr. Mayer reports receiving grant support from Gilead, Merck, and Bristol-Myers Squibb; Dr. Kallas reports serving on a data and safety monitoring board for Merck; Dr. Schechter reports receiving consulting fees and grants from Gilead; Drs. Liu and Anderson report receiving donations of study drug from Gilead for various PrEP projects; and Drs. Jaffe and Rooney report being employees of Gilead Sciences and owning stock in the company. No other potential conflict of interest relevant to this article was reported. Disclosure forms provided by the authors are available with the full text of this article at NEJM.org. NR 33 TC 1530 Z9 1564 U1 16 U2 161 PU MASSACHUSETTS MEDICAL SOC PI WALTHAM PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD DEC 30 PY 2010 VL 363 IS 27 BP 2587 EP 2599 DI 10.1056/NEJMoa1011205 PG 13 WC Medicine, General & Internal SC General & Internal Medicine GA 700SD UT WOS:000285763700004 PM 21091279 ER PT J AU Kuhns, DB Alvord, WG Heller, T Feld, JJ Pike, KM Marciano, BE Uzel, G DeRavin, SS Priel, DAL Soule, BP Zarember, KA Malech, HL Holland, SM Gallin, JI AF Kuhns, Douglas B. Alvord, W. Gregory Heller, Theo Feld, Jordan J. Pike, Kristen M. Marciano, Beatriz E. Uzel, Gulbu DeRavin, Suk See Priel, Debra A. Long Soule, Benjamin P. Zarember, Kol A. Malech, Harry L. Holland, Steven M. Gallin, John I. TI Residual NADPH Oxidase and Survival in Chronic Granulomatous Disease. SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Article ID HEMATOLOGICALLY IMPORTANT MUTATIONS; MARROW-TRANSPLANTATION; RESPIRATORY-BURST; INTERFERON-GAMMA; INVOLVEMENT; DEFICIENCY; GP91-PHOX; INFECTION; THERAPY; DOMAIN AB Background: Failure to generate phagocyte-derived superoxide and related reactive oxygen intermediates (ROIs) is the major defect in chronic granulomatous disease, causing recurrent infections and granulomatous complications. Chronic granulomatous disease is caused by missense, nonsense, frameshift, splice, or deletion mutations in the genes for p22(sup phox), p40(sup phox), p47(sup phox), p67(sup phox) (autosomal chronic granulomatous disease), or gp91(sup phox) (X-linked chronic granulomatous disease), which result in variable production of neutrophil-derived ROIs. We hypothesized that residual ROI production might be linked to survival in patients with chronic granulomatous disease. Methods: We assessed the risks of illness and death among 287 patients with chronic granulomatous disease from 244 kindreds. Residual ROI production was measured with the use of superoxide-dependent ferricytochrome c reduction and flow cytometry with dihydrorhodamine oxidation assays. Expression of NADPH oxidase component protein was detected by means of immunoblotting, and the affected genes were sequenced to identify causal mutations. Results: Survival of patients with chronic granulomatous disease was strongly associated with residual ROI production as a continuous variable, independently of the specific gene affected. Patients with mutations in p47(sup phox) and most missense mutations in gp91(sup phox) (with the exception of missense mutations in the nucleotide-binding and heme-binding domains) had more residual ROI production than patients with nonsense, frameshift, splice, or deletion mutations in gp91(sup phox). After adolescence, mortality curves diverged according to the extent of residual ROI production. Conclusions: Patients with chronic granulomatous disease and modest residual production of ROI have significantly less severe illness and a greater likelihood of long-term survival than patients with little residual ROI production. The production of residual ROI is predicted by the specific NADPH oxidase mutation, regardless of the specific gene affected, and it is a predictor of survival in patients with chronic granulomatous disease. (Funded by the National Institutes of Health.) N Engl J Med 2010;363:2600-10. C1 [DeRavin, Suk See; Soule, Benjamin P.; Zarember, Kol A.; Malech, Harry L.; Gallin, John I.] NIAID, Host Def Lab, NIH, Bethesda, MD 20892 USA. [Kuhns, Douglas B.; Priel, Debra A. Long] SAIC Frederick, Clin Serv Program, Frederick, MD USA. [Pike, Kristen M.] SAIC Frederick, Lab Mol Technol, Frederick, MD USA. [Alvord, W. Gregory] NCI Frederick, Biostat Consulting Div, Data Management Serv, Frederick, MD USA. [Heller, Theo] NIDDKD, Liver Dis Branch, Bethesda, MD USA. [Marciano, Beatriz E.; Uzel, Gulbu; Holland, Steven M.] NIAID, Lab Clin Infect Dis, NIH, Bethesda, MD 20892 USA. [DeRavin, Suk See; Soule, Benjamin P.; Zarember, Kol A.; Malech, Harry L.; Gallin, John I.] NIAID, Host Def Lab, NIH, Bethesda, MD 20892 USA. [Feld, Jordan J.] Univ Toronto, Toronto Western Hosp, McLaughlin Rotman Ctr Global Hlth, Ctr Liver, Toronto, ON M5T 2S8, Canada. RP Gallin, JI (reprint author), NIAID, Host Def Lab, NIH, Bldg 10,Rm 6-2551, Bethesda, MD 20892 USA. EM jgallin@cc.nih.gov FU National Institute of Allergy and Infectious Diseases [Z01-AI-000155, Z01-AI-000645, Z01-AI-00646-06]; National Institute of Diabetes and Digestive and Kidney Diseases [ZIA DK075008-04 LDB]; National Cancer Institute [HH-SN261200800001E]; National Institutes of Health FX Supported by intramural grants from the National Institute of Allergy and Infectious Diseases (Z01-AI-000155, Z01-AI-000645, and Z01-AI-00646-06), a grant from the National Institute of Diabetes and Digestive and Kidney Diseases (ZIA DK075008-04 LDB), and a contract from the National Cancer Institute (HH-SN261200800001E).; Funded by the National Institutes of Health NR 40 TC 166 Z9 170 U1 0 U2 9 PU MASSACHUSETTS MEDICAL SOC PI WALTHAM PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD DEC 30 PY 2010 VL 363 IS 27 BP 2600 EP 2610 DI 10.1056/NEJMoa1007097 PG 11 WC Medicine, General & Internal SC General & Internal Medicine GA 700SD UT WOS:000285763700005 PM 21190454 ER PT J AU Arinaminpathy, N Grenfell, B AF Arinaminpathy, Nimalan Grenfell, Bryan TI Dynamics of Glycoprotein Charge in the Evolutionary History of Human Influenza SO PLOS ONE LA English DT Article ID A VIRUS; LINKED GLYCOSYLATION; RECEPTOR-BINDING; ANTIGENIC DRIFT; HEMAGGLUTININ; PHENOTYPE; TURKEYS; GLYCANS; DOMAIN; SITES AB Background: Influenza viruses show a significant capacity to evade host immunity; this is manifest both as large occasional jumps in the antigenic phenotype of viral surface molecules and in gradual antigenic changes leading to annual influenza epidemics in humans. Recent mouse studies show that avidity for host cells can play an important role in polyclonal antibody escape, and further that electrostatic charge of the hemagglutinin glycoprotein can contribute to such avidity. Methodology/Principal Findings: We test the role of glycoprotein charge on sequence data from the three major subtypes of influenza A in humans, using a simple method of calculating net glycoprotein charge. Of all subtypes, H3N2 in humans shows a striking pattern of increasing positive charge since its introduction in 1968. Notably, this trend applies to both hemagglutinin and neuraminidase glycoproteins. In the late 1980s hemagglutinin charge reached a plateau, while neuraminidase charge started to decline. We identify key groups of amino acid sites involved in this charge trend. Conclusions/Significance: To our knowledge these are the first indications that, for human H3N2, net glycoprotein charge covaries strongly with antigenic drift on a global scale. Further work is needed to elucidate how such charge interacts with other immune escape mechanisms, such as glycosylation, and we discuss important questions arising for future study. C1 [Arinaminpathy, Nimalan; Grenfell, Bryan] Princeton Univ, Dept Ecol & Evolut Biol, Princeton, NJ 08544 USA. [Grenfell, Bryan] NIH, Fogarty Int Ctr, Bethesda, MD 20892 USA. RP Arinaminpathy, N (reprint author), Princeton Univ, Dept Ecol & Evolut Biol, Princeton, NJ 08544 USA. EM nimpathy@princeton.edu FU National Institutes of Health [R01 GM083983-01]; National Science Foundation [EF-0742373]; Department of Homeland Security Science and Technology Directorate; Fogarty International Center, National Institutes of Health FX This research was supported by the National Institutes of Health grant R01 GM083983-01 (www.nih.gov). Bryan Grenfell was also supported by the National Science Foundation grant EF-0742373 and the Research and Policy for Infectious Disease Dynamics (RAPIDD) program of the Department of Homeland Security Science and Technology Directorate and the Fogarty International Center, National Institutes of Health. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 25 TC 18 Z9 18 U1 1 U2 7 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 185 BERRY ST, STE 1300, SAN FRANCISCO, CA 94107 USA SN 1932-6203 J9 PLOS ONE JI PLoS One PD DEC 30 PY 2010 VL 5 IS 12 AR e15674 DI 10.1371/journal.pone.0015674 PG 7 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 701DD UT WOS:000285793600025 PM 21209885 ER PT J AU LeClair, CA Boxer, MB Thomas, CJ Maloney, DJ AF LeClair, Christopher A. Boxer, Matthew B. Thomas, Craig J. Maloney, David J. TI Total synthesis of LL-Z1640-2 utilizing a late-stage intramolecular Nozaki-Hiyama-Kishi reaction SO TETRAHEDRON LETTERS LA English DT Article ID RESORCYLIC ACID LACTONES; CONVERGENT STEREOSPECIFIC SYNTHESIS; VINYLIC ORGANOBORANES; ALKENYLBORONIC ACIDS; EFFICIENT SYNTHESIS; HYPOTHEMYCIN; KINASE; STEREOCHEMISTRY; INHIBITION; MACROLIDES AB A total synthesis of LL-Z1640-2 (2), a potent and selective kinase inhibitor, has been completed. The key step of the convergent synthesis utilized a late-stage intramolecular Nozaki-Hiyama-Kishi (NHK) reaction to close the macrocycle at the C6'-C7' bond. Published by Elsevier Ltd. C1 [LeClair, Christopher A.; Boxer, Matthew B.; Thomas, Craig J.; Maloney, David J.] NHGRI, NIH Chem Genom Ctr, NIH, Rockville, MD 20850 USA. RP Thomas, CJ (reprint author), NHGRI, NIH Chem Genom Ctr, NIH, 9800 Med Ctr Dr,Bldg B,Room 2055,MSC 3370, Bethesda, MD 20892 USA. EM craigt@mail.nih.gov FU Molecular Libraries Initiative of the National Institutes of Health Roadmap for Medical Research; National Human Genome Research Institute; National Institutes of Health FX The authors thank William Leister for his assistance with normal and reverse phase purification techniques. This research was supported by the Molecular Libraries Initiative of the National Institutes of Health Roadmap for Medical Research, the Intramural Research Program of the National Human Genome Research Institute, and the National Institutes of Health. NR 45 TC 15 Z9 15 U1 4 U2 36 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0040-4039 J9 TETRAHEDRON LETT JI Tetrahedron Lett. PD DEC 29 PY 2010 VL 51 IS 52 BP 6852 EP 6855 DI 10.1016/j.tetlet.2010.10.092 PG 4 WC Chemistry, Organic SC Chemistry GA 699NP UT WOS:000285670400014 PM 21516235 ER PT J AU Kanno, T Nishizaki, T Proia, RL Kajimoto, T Jahangeer, S Okada, T Nakamura, S AF Kanno, T. Nishizaki, T. Proia, R. L. Kajimoto, T. Jahangeer, S. Okada, T. Nakamura, S. TI REGULATION OF SYNAPTIC STRENGTH BY SPHINGOSINE 1-PHOSPHATE IN THE HIPPOCAMPUS SO NEUROSCIENCE LA English DT Article DE sphingosine kinase; sphingosine 1 phosphate S1P receptor; long term potentiation; hippocampus; memory ID LONG-TERM POTENTIATION; NERVOUS-SYSTEM; LYSOPHOSPHOLIPID RECEPTORS; SPHINGOSINE-1-PHOSPHATE; CELL; INVOLVEMENT; MICE AB Although the hippocampus is a brain region involved in short term memory, the molecular mechanisms underlying memory formation are not completely under stood Here we show that sphingosine 1 phosphate (SIP) plays a pivotal role in the formation of memory Addition of SIP to rat hippocampal slices increased the rate of AMPA receptor mediated miniature excitatory postsynaptic cur rents (mEPSCs) recorded from the CA3 region of the hippocampus In addition long term potentiation (LTP) observed in the CA3 region was potently inhibited by a sphingosine kinase (SphK) inhibitor and this inhibition was fully reversed by SIP LIP was impaired in hippocampal slices specifically in the CA3 region obtained from SphK1 knockout mice, which correlates well with the poor performance of these animals in the Morris water maze test These results strongly suggest that SphK/S1P receptor signaling plays an important role in excitatory synaptic transmission in the CA3 region of hippocampus and has profound effects on hippocampal function such as spatial learning (C) 2010 IBRO Published by Elsevier Ltd All rights reserved C1 [Kajimoto, T.; Jahangeer, S.; Okada, T.; Nakamura, S.] Kobe Univ, Grad Sch Med, Dept Mol & Cellular Biol, Div Biochem, Kobe, Hyogo 6500017, Japan. [Proia, R. L.] NIDDK, Genet Dev & Dis Branch, NIH, Bethesda, MD 20892 USA. [Kanno, T.; Nishizaki, T.] Hyogo Coll Med, Dept Physiol, Nishinomiya, Hyogo 6638501, Japan. RP Nakamura, S (reprint author), Kobe Univ, Grad Sch Med, Dept Mol & Cellular Biol, Div Biochem, Kobe, Hyogo 6500017, Japan. RI Proia, Richard/A-7908-2012 FU Ministry of Education Science Sports and Culture of Japan; Japan Society for the Promotion of Science; Polish Academy of Sciences; National Institutes of Health National Institute of Diabetes and Digestive and Kidney Diseases USA; Osaka Medical Research Foundation for Incurable Diseases FX This work was supported in part by a Grant in-Aid for Scientific Research (C) and a Grant-in-Aid for Scientific Research on Priority Areas-Molecular Brain Science from the Ministry of Education Science Sports and Culture of Japan the Bilateral Exchange Program between Japan Society for the Promotion of Science and Polish Academy of Sciences the Intramural Research Program of the National Institutes of Health National Institute of Diabetes and Digestive and Kidney Diseases USA and the Osaka Medical Research Foundation for Incurable Diseases NR 26 TC 38 Z9 38 U1 0 U2 5 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0306-4522 J9 NEUROSCIENCE JI Neuroscience PD DEC 29 PY 2010 VL 171 IS 4 BP 973 EP 980 DI 10.1016/j.neuroscience.2010.10.021 PG 8 WC Neurosciences SC Neurosciences & Neurology GA 693NO UT WOS:000285231000002 PM 20950672 ER PT J AU Silverman, JL Yang, M Turner, SM Katz, AM Bell, DB Koenig, JI Crawley, JN AF Silverman, J. L. Yang, M. Turner, S. M. Katz, A. M. Bell, D. B. Koenig, J. I. Crawley, J. N. TI LOW STRESS REACTIVITY AND NEUROENDOCRINE FACTORS IN THE BTBR T(+)tf/J MOUSE MODEL OF AUTISM SO NEUROSCIENCE LA English DT Article DE autism; mouse models BTBR ID CORTICOTROPIN-RELEASING-FACTOR; ANXIETY-LIKE BEHAVIOR; TAIL SUSPENSION TEST; SOCIAL APPROACH BEHAVIORS; MELANOCYTE-STIMULATING HORMONE; GROOMING ANALYSIS ALGORITHM; COMPLEX MOVEMENT SEQUENCE; DOPAMINE D1 AGONISTS; MUTANT MICE DISPLAY; CRF-DEFICIENT MICE AB Autism is a neurodevelopmental disorder characterized by abnormal reciprocal social interactions, communication deficits, and repetitive behaviors with restricted interests BTBR T+tf/J (BTBR) is an inbred mouse strain that displays robust behavioral phenotypes with analogies to all three of the diagnostic symptoms of autism, including low social interactions, reduced vocalizations in social settings, and high levels of repetitive self grooming Autism relevant phenotypes in BTBR offer translational tools to discover neurochemical mechanisms underlying unusual mouse behaviors relevant to symptoms of autism Because repetitive self grooming in mice may be a displacement behavior elevated by stressors, we investigated neuroendocrine markers of stress and behavioral reactivity to stressors in BTBR mice, as compared to C57BL/6J (86), a standard inbred strain with high sociability Radioimmunoassays replicated previous findings that circulating corticosterone is higher in BTBR than in B6 Higher basal glucocorticoid receptor mRNA and higher oxytocin peptide levels were detected in the brains of BTBR as compared to B6 No significant differences were detected in corticotrophin releasing factor (CRF) peptide or CRF mRNA In response to behavioral stressors, BTBR and B6 were generally similar on behavioral tasks including stress-induced hyperthermia elevated plus maze light dark exploration tail flick acoustic startle and prepulse inhibition BTBR displayed less reactivity than B6 to a noxious thermal stimulus in the hot plate, and less immobility than B6 in both the forced swim and tail suspension depression-related tasks BTBR, therefore, exhibited lower depression like scores than 136 on two standard tests sensitive to anti depressants, did not differ from B6 on two well validated anxiety like behaviors, and did not exhibit unusual stress reactivity to sensory stimuli Our findings support the interpretation that autism relevant social deficits, vocalizations, and repetitive behaviors are not the result of abnormal stress reactivity in the BTBR mouse model of autism Published by Elsevier Ltd on behalf of IBRO C1 [Silverman, J. L.; Yang, M.; Turner, S. M.; Katz, A. M.; Crawley, J. N.] NIMH, Lab Behav Neurosci, Intramural Res Program, Bethesda, MD 20892 USA. [Bell, D. B.; Koenig, J. I.] Univ Maryland, Sch Med, Dept Psychiat, Maryland Psychiat Res Ctr, Catonsville, MD 21228 USA. RP Silverman, JL (reprint author), NIMH, Lab Behav Neurosci, Intramural Res Program, Bethesda, MD 20892 USA. FU National Institute of Mental Health; Intramural Research Program; [R01 MH073826 JIK] FX Supported by the National Institute of Mental Health Intramural Research Program and R01 MH073826 JIK NR 150 TC 56 Z9 56 U1 4 U2 12 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0306-4522 J9 NEUROSCIENCE JI Neuroscience PD DEC 29 PY 2010 VL 171 IS 4 BP 1197 EP 1208 DI 10.1016/j.neuroscience.2010.09.059 PG 12 WC Neurosciences SC Neurosciences & Neurology GA 693NO UT WOS:000285231000021 PM 20888890 ER PT J AU Hong, SB Oh, H Valera, VA Baba, M Schmidt, LS Linehan, WM AF Hong, Seung-Beom Oh, HyoungBin Valera, Vladimir A. Baba, Masaya Schmidt, Laura S. Linehan, W. Marston TI Inactivation of the FLCN Tumor Suppressor Gene Induces TFE3 Transcriptional Activity by Increasing Its Nuclear Localization SO PLOS ONE LA English DT Article ID HOGG-DUBE-SYNDROME; RENAL-CELL CARCINOMA; MELANOMA PROTEIN-B; BHD GENE; THERAPEUTIC TARGET; MTOR ACTIVATION; BREAST-CANCER; AURISTATIN-E; MITF; MICROPHTHALMIA AB Background: Germline mutations in a tumor suppressor gene FLCN lead to development of fibrofolliculomas, lung cysts and renal cell carcinoma (RCC) in Birt-Hogg-Dube syndrome. TFE3 is a member of the MiTF/TFE transcription factor family and Xp11.2 translocations found in sporadic RCC involving TFE3 result in gene fusions and overexpression of chimeric fusion proteins that retain the C-terminal DNA binding domain of TFE3. We found that GPNMB expression, which is regulated by MiTF, was greatly elevated in renal cancer cells harboring either TFE3 translocations or FLCN inactivation. Since TFE3 is implicated in RCC, we hypothesized that elevated GPNMB expression was due to increased TFE3 activity resulting from the inactivation of FLCN. Methodology/Principal Findings: TFE3 knockdown reduced GPNMB expression in renal cancer cells harboring either TFE3 translocations or FLCN inactivation. Moreover, FLCN knockdown induced GPNMB expression in FLCN-restored renal cancer cells. Conversely, wildtype FLCN suppressed GPNMB expression in FLCN-null cells. FLCN inactivation was correlated with increased TFE3 transcriptional activity accompanied by its nuclear localization as revealed by elevated GPNMB mRNA and protein expression, and predominantly nuclear immunostaining of TFE3 in renal cancer cells, mouse embryo fibroblast cells, mouse kidneys and mouse and human renal tumors. Nuclear localization of TFE3 was associated with TFE3 post-translational modifications including decreased phosphorylation. Conclusions/Significance: Increased TFE3 activity is a downstream event induced by FLCN inactivation and is likely to be important for renal tumor development. This study provides an important novel mechanism for induction of TFE3 activity in addition to TFE3 overexpression resulting from Xp11.2 translocations, suggesting that TFE3 may be more broadly involved in tumorigenesis. C1 [Hong, Seung-Beom; Oh, HyoungBin; Valera, Vladimir A.; Baba, Masaya; Schmidt, Laura S.; Linehan, W. Marston] NCI, Urol Oncol Branch, Ctr Canc Res, Bethesda, MD 20892 USA. [Schmidt, Laura S.] NCI, Basic Sci Program, SAIC Frederick Inc, Frederick, MD 21701 USA. RP Hong, SB (reprint author), NCI, Urol Oncol Branch, Ctr Canc Res, Bethesda, MD 20892 USA. EM linehanm@mail.nih.gov RI Baba, Masaya/L-7490-2013; di Ronza, Alberto/H-7674-2016 OI Baba, Masaya/0000-0002-5308-6683; di Ronza, Alberto/0000-0002-9813-5143 FU National Institutes of Health, National Cancer Institute, Center for Cancer Research; National Cancer Institute, National Institutes of Health [HHSN261200800001E]; NCI-Frederick FX This research was supported by the Intramural Research Program of the National Institutes of Health, National Cancer Institute, Center for Cancer Research. This project has been funded with federal funds from the National Cancer Institute, National Institutes of Health, under contract HHSN261200800001E. The content of this publication does not necessarily reflect the views or policies of the Department of Heath and Human Services, nor does mention of trade names, commercial products, or organizations imply endorsement by the U.S. Government. The funder has no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. SAIC-Frederick is the Operation and Technical Support contractor to the National Cancer Institute at Frederick (NCI-Frederick), a federal laboratory. SAIC-Frederick, as the contractor, is the recipient of NCI-Frederick funding and has not independently funded this research. NR 43 TC 47 Z9 51 U1 0 U2 4 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 185 BERRY ST, STE 1300, SAN FRANCISCO, CA 94107 USA SN 1932-6203 J9 PLOS ONE JI PLoS One PD DEC 29 PY 2010 VL 5 IS 12 AR e15793 DI 10.1371/journal.pone.0015793 PG 12 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 701CZ UT WOS:000285793200054 PM 21209915 ER PT J AU Lei, HY Fukushige, T Niu, W Sarov, M Reinke, V Krause, M AF Lei, Haiyan Fukushige, Tetsunari Niu, Wei Sarov, Mihail Reinke, Valerie Krause, Michael TI A Widespread Distribution of Genomic CeMyoD Binding Sites Revealed and Cross Validated by ChIP-Chip and ChIP-Seq Techniques SO PLOS ONE LA English DT Article ID CAENORHABDITIS-ELEGANS; C-ELEGANS; MUSCLE DEVELOPMENT; GENE-EXPRESSION; PROTEIN; TRANSCRIPTION; EMBRYO; MYOD; REGULATOR; INTESTINE AB Identifying transcription factor binding sites genome-wide using chromatin immunoprecipitation (ChIP)-based technology is becoming an increasingly important tool in addressing developmental questions. However, technical problems associated with factor abundance and suitable ChIP reagents are common obstacles to these studies in many biological systems. We have used two completely different, widely applicable methods to determine by ChIP the genome-wide binding sites of the master myogenic regulatory transcription factor HLH-1 (CeMyoD) in C. elegans embryos. The two approaches, ChIP-seq and ChIP-chip, yield strongly overlapping results revealing that HLH-1 preferentially binds to promoter regions of genes enriched for E-box sequences (CANNTG), known binding sites for this well-studied class of transcription factors. HLH-1 binding sites were enriched upstream of genes known to be expressed in muscle, consistent with its role as a direct transcriptional regulator. HLH-1 binding was also detected at numerous sites unassociated with muscle gene expression, as has been previously described for its mouse homolog MyoD. These binding sites may reflect several additional functions for HLH-1, including its interactions with one or more co-factors to activate (or repress) gene expression or a role in chromatin organization distinct from direct transcriptional regulation of target genes. Our results also provide a comparison of ChIP methodologies that can overcome limitations commonly encountered in these types of studies while highlighting the complications of assigning in vivo functions to identified target sites. C1 [Lei, Haiyan; Fukushige, Tetsunari; Krause, Michael] NIDDK, NIH, Bethesda, MD 20892 USA. [Niu, Wei] Yale Univ, Dept Mol, New Haven, CT USA. [Sarov, Mihail] Max Planck Inst Mol Cell Biol & Genet, Dresden, Germany. [Reinke, Valerie] Yale Univ, Sch Med, Dept Genet, New Haven, CT 06510 USA. RP Lei, HY (reprint author), NIDDK, NIH, Bethesda, MD 20892 USA. EM mwkrause@helix.nih.gov RI NUI, WEI/B-8300-2011; OI Krause, Michael/0000-0001-6127-3940 FU National Institutes of Health, National Institute of Diabetes and Digestive and Kidney Diseases; National Human Genome Research Institute [U01HG004267] FX This work was supported, in part, by the Intramural Research Program of the National Institutes of Health, National Institute of Diabetes and Digestive and Kidney Diseases. Support also came from the Model Organism Encylopedia of DNA Elements (modENCODE) project funded by grant U01HG004267 from the National Human Genome Research Institute. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 45 TC 13 Z9 13 U1 0 U2 3 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA SN 1932-6203 J9 PLOS ONE JI PLoS One PD DEC 29 PY 2010 VL 5 IS 12 AR e15898 DI 10.1371/journal.pone.0015898 PG 12 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 701CZ UT WOS:000285793200070 PM 21209968 ER PT J AU Ott, PA Hamilton, A Min, C Safarzadeh-Amiri, S Goldberg, L Yoon, J Yee, H Buckley, M Christos, PJ Wright, JJ Polsky, D Osman, I Liebes, L Pavlick, AC AF Ott, Patrick A. Hamilton, Anne Min, Christina Safarzadeh-Amiri, Sara Goldberg, Lauren Yoon, Joanne Yee, Herman Buckley, Michael Christos, Paul J. Wright, John J. Polsky, David Osman, Iman Liebes, Leonard Pavlick, Anna C. TI A Phase II Trial of Sorafenib in Metastatic Melanoma with Tissue Correlates SO PLOS ONE LA English DT Article ID STAGE-IV MELANOMA; MALIGNANT-MELANOMA; B-RAF; BRAF; MUTATIONS; DACARBAZINE; KIT; PROGRESSION; CARCINOMA; IMATINIB AB Background: Sorafenib monotherapy in patients with metastatic melanoma was explored in this multi-institutional phase II study. In correlative studies the impact of sorafenib on cyclin D1 and Ki67 was assessed. Methodology/Principal Findings: Thirty-six patients treatment-naive advanced melanoma patients received sorafenib 400 mg p.o. twice daily continuously. Tumor BRAF V600E mutational status was determined by routine DNA sequencing and mutation-specific PCR (MSPCR). Immunohistochemistry (IHC) staining for cyclin D1 and Ki67 was performed on available pre- and post treatment tumor samples. The main toxicities included diarrhea, alopecia, rash, mucositis, nausea, hand-foot syndrome, and intestinal perforation. One patient had a RECIST partial response (PR) lasting 175 days. Three patients experienced stable disease (SD) with a mean duration of 37 weeks. Routine BRAF V600E sequencing yielded 27 wild-type (wt) and 6 mutant tumors, whereas MSPCR identified 12 wt and 18 mutant tumors. No correlation was seen between BRAF V600E mutational status and clinical activity. No significant changes in expression of cyclin D1 or Ki67 with sorafenib treatment were demonstrable in the 15 patients with pre-and post-treatment tumor samples. Conclusions/Significance: Sorafenib monotherapy has limited activity in advanced melanoma patients. BRAF V600E mutational status of the tumor was not associated with clinical activity and no significant effect of sorafenib on cyclin D1 or Ki67 was seen, suggesting that sorafenib is not an effective BRAF inhibitor or that additional signaling pathways are equally important in the patients who benefit from sorafenib. registration: C1 [Ott, Patrick A.; Min, Christina; Safarzadeh-Amiri, Sara; Goldberg, Lauren; Buckley, Michael; Osman, Iman; Liebes, Leonard; Pavlick, Anna C.] NYU, Sch Med, Dept Med Oncol, New York, NY 10003 USA. [Yee, Herman; Polsky, David] NYU, Sch Med, Dept Pathol, New York, NY USA. [Yoon, Joanne; Polsky, David; Osman, Iman; Pavlick, Anna C.] NYU, Sch Med, Dept Dermatol, New York, NY USA. [Hamilton, Anne] Royal Prince Alfred Hosp, Sydney Canc Ctr, Sydney, NSW, Australia. [Hamilton, Anne] Univ Sydney, Sydney, NSW 2006, Australia. [Hamilton, Anne] Sydney Melanoma Unit, Sydney, NSW, Australia. [Christos, Paul J.] Weill Cornell Med Coll, Div Biostat & Epidemiol, New York, NY USA. [Wright, John J.] NCI, Invest Drug Branch, Bethesda, MD 20892 USA. RP Ott, PA (reprint author), NYU, Sch Med, Dept Med Oncol, New York, NY 10003 USA. EM anna.pavlick@nyumc.org FU United States Department of Health and Human Service [N01-CM-17103, N01-CM-62204] FX This work was supported by the United States Department of Health and Human Service contracts [N01-CM-17103 and N01-CM-62204]. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 38 TC 54 Z9 56 U1 0 U2 3 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 185 BERRY ST, STE 1300, SAN FRANCISCO, CA 94107 USA SN 1932-6203 J9 PLOS ONE JI PLoS One PD DEC 29 PY 2010 VL 5 IS 12 AR e15588 DI 10.1371/journal.pone.0015588 PG 9 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 701CZ UT WOS:000285793200030 PM 21206909 ER PT J AU Martos, A Alfonso, C Lopez-Navajas, P Ahijado-Guzman, R Mingorance, J Minton, AP Rivas, G AF Martos, Ariadna Alfonso, Carlos Lopez-Navajas, Pilar Ahijado-Guzman, Ruben Mingorance, Jesus Minton, Allen P. Rivas, German TI Characterization of Self-Association and Heteroassociation of Bacterial Cell Division Proteins FtsZ and ZipA in Solution by Composition Gradient-Static Light Scattering SO BIOCHEMISTRY LA English DT Article ID ESCHERICHIA-COLI; SEPTAL RING; QUANTITATIVE CHARACTERIZATION; SEDIMENTATION EQUILIBRIUM; PROTOFILAMENTS; RECRUITMENT; ENERGETICS; COMPONENT; POLYMERS; MONOMER AB We have characterized the self-association of FtsZ in its GDP-bound state (GDP-FtsZ) and the heteroassociation of FtsZ and a soluble recombinant ZipA (sZipA) lacking the N-terminal transmembrane domain by means of composition gradient static light scattering (CG-SLS) and by measurement of sedimentation equilibrium. CG-SLS experiments at high ionic strengths and in the presence of 5 mM Mg(2+) show that, while FtsZ self-associates in a noncooperative fashion, sZipA acts as a monomer. CG-SLS data obtained from mixtures of FtsZ (A) and sZipA (B) in the presence of Mg(2+) are quantitatively described by an equilibrium model that takes into account significant scattering contributions from B, A(1), A(2), A(3), A(4), A(5), A(6), A(1)B, A(2)B, A(3)B, and A(4)B. However, in the absence of Mg(2+) (with EDTA), the data are best explained by an equilibrium model in which only B, A(1), A(2), A(3), A(1)B, and A(2)B contribute significantly to scattering. The best-fit molecular weights of monomeric A and B are in good agreement with values calculated from amino acid composition and with values obtained from sedimentation equilibrium. The latter technique also confirmed the interaction between sZipA and GDP-FtsZ. Moreover, the association model that best describes the CG-SLS data is in qualitative agreement with the sedimentation data. From these results, it follows that the binding of sZipA to GDP-FtsZ is of moderate affinity and does not significantly affect the interactions between FtsZ monomers. Under the working conditions used, only one sZipA binds to FtsZ oligomers with a length of six at most. The observed behavior would be compatible with FtsZ fibrils being anchored in vivo to the bacterial inner plasma membrane by substoichiometric binding of membrane-bound ZipA. C1 [Martos, Ariadna; Alfonso, Carlos; Lopez-Navajas, Pilar; Ahijado-Guzman, Ruben; Rivas, German] CSIC, Ctr Invest Biol, Chem & Phys Biol Program, E-28040 Madrid, Spain. [Mingorance, Jesus] CSIC, Ctr Nacl Biotecnol, Dept Mol Biotechnol, E-28040 Madrid, Spain. [Minton, Allen P.] NIDDKD, Sect Phys Biochem, Lab Biochem & Genet, NIH, Bethesda, MD 20892 USA. RP Rivas, G (reprint author), CSIC, Ctr Invest Biol, Chem & Phys Biol Program, Ramiro de Maeztu 9, E-28040 Madrid, Spain. EM minton@helix.nih.gov; grivas@cib.csic.es RI Mingorance, Jesus/B-7562-2009; Alfonso, Carlos/K-1316-2014; Ahijado-Guzman, Ruben/F-7934-2016; OI Mingorance, Jesus/0000-0001-6173-5711; Alfonso, Carlos/0000-0001-7165-4800; Ahijado-Guzman, Ruben/0000-0002-9863-0443; Minton, Allen/0000-0001-8459-1247; Rivas, German/0000-0003-3450-7478 FU Plan Nacional (Ministerio de Ciencia e Innovacion, Spain) [BIO2008-04478-C03]; European Commision [DIVI-NOCELL FP/HEALTH-F3-2009-223432]; Comunidad de Madrid [COMBACT S-BIO-0260/2006]; National Institute of Diabetes and Digestive and Kidney Diseases; European Social Fund FX This work was supported by Plan Nacional (Ministerio de Ciencia e Innovacion, Spain) Grants BIO2008-04478-C03 to G.R. Grant DIVI-NOCELL FP/HEALTH-F3-2009-223432 (European Commision) to G.R., and Grant COMBACT S-BIO-0260/2006 (Comunidad de Madrid) to J.M. and G.R. A.M. is a predoctoral fellow from the Ministerio de Ciencia e Innovacion of Spain. P.L.-N. was a recipient of a predoctoral fellowship from the Comunidad de Madrid. The research of A.P.M. is supported by the Intramural Research Program of the National Institute of Diabetes and Digestive and Kidney Diseases. J.M. was the recipient of a Ramon y Cajal fellowship financed by the Spanish Ministerio de Ciencia e Innovacion and the European Social Fund. NR 34 TC 21 Z9 21 U1 0 U2 3 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0006-2960 J9 BIOCHEMISTRY-US JI Biochemistry PD DEC 28 PY 2010 VL 49 IS 51 BP 10780 EP 10787 DI 10.1021/bi101495x PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 696GF UT WOS:000285429200004 PM 21082789 ER PT J AU Buch, I Fishelovitch, D London, N Raveh, B Wolfson, HJ Nussinov, R AF Buch, Idit Fishelovitch, Dan London, Nir Raveh, Barak Wolfson, Haim J. Nussinov, Ruth TI Allosteric Regulation of Glycogen Synthase Kinase 3 beta: A Theoretical Study SO BIOCHEMISTRY LA English DT Article ID DEPENDENT PROTEIN-KINASE; STRUCTURAL BASIS; MOLECULAR-DYNAMICS; CRYSTAL-STRUCTURE; TYROSINE PHOSPHORYLATION; SUBSTRATE-SPECIFICITY; CATALYTIC-ACTIVITY; BETA-CATENIN; INHIBITORS; KINASE-3-BETA AB Glycogen synthase kinase 3 beta (GSK-3 beta) is a serine-threonine kinase belonging to the CMGC family that plays a key role in many biological processes, such as glucose metabolism, cell cycle regulation, and proliferation. Like most protein kinases, GSK-3 beta is regulated via multiple pathways and sites. We performed all-atom molecular dynamics simulations on the unphosphorylated and phosphorylated unbound GSK-3 beta and the phosphorylated GSK-3 beta bound to a peptide substrate, its product, and a derived inhibitor. We found that GSK-3 beta autophosphorylation at residue Tyr(216) results in widening of the catalytic groove, thereby facilitating substrate access. In addition, we studied the interactions of the phosphorylated GSK-3 beta with a substrate and peptide inhibitor located at the active site and observed higher affinity of the inhibitor to the kinase. Furthermore, we detected a potential remote binding site which was previously identified in other kinases. In agreement with experiments we observed that binding of specific peptides at this remote site leads to stabilization of the activation loop located in the active site. We speculate that this stabilization could enhance the catalytic activity of the kinase. We point to this remote site as being structurally conserved and suggest that the allosteric phenomenon observed here may occur in the protein kinase superfamily. C1 [Buch, Idit; Fishelovitch, Dan; Nussinov, Ruth] Tel Aviv Univ, Sackler Fac Med, Sackler Inst Mol Med, Dept Human Mol Genet & Biochem, IL-69978 Tel Aviv, Israel. [London, Nir; Raveh, Barak] Hebrew Univ Jerusalem, Hadassah Med Sch, Fac Med, Dept Microbiol & Mol Genet,Inst Med Red IMRIC, IL-91120 Jerusalem, Israel. [Raveh, Barak; Wolfson, Haim J.] Tel Aviv Univ, Raymond & Beverly Sackler Fac Exact Sci, Sch Comp Sci, IL-69978 Tel Aviv, Israel. [Nussinov, Ruth] NCI Frederick, SAIC Frederick Inc, Ctr Canc Res Nanobiol Program, Frederick, MD 21702 USA. RP Nussinov, R (reprint author), Tel Aviv Univ, Sackler Fac Med, Sackler Inst Mol Med, Dept Human Mol Genet & Biochem, IL-69978 Tel Aviv, Israel. EM ruthnu@helix.nih.gov FU National Cancer Institute, National Institutes of Health [HHSN261200800001E]; NIH, National Cancer Institute, Center for Cancer Research 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 number HHSN261200800001E. This research was supported (in part) by the Intramural Research Program of the NIH, National Cancer Institute, Center for Cancer Research. NR 61 TC 13 Z9 13 U1 0 U2 5 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0006-2960 J9 BIOCHEMISTRY-US JI Biochemistry PD DEC 28 PY 2010 VL 49 IS 51 BP 10890 EP 10901 DI 10.1021/bi100822q PG 12 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 696GF UT WOS:000285429200016 PM 21105670 ER PT J AU Jin, LH Tabe, Y Kojima, K Zhou, YX Pittaluga, S Konopleva, M Miida, T Raffeld, M AF Jin, Linhua Tabe, Yoko Kojima, Kensuke Zhou, Yixin Pittaluga, Stefania Konopleva, Marina Miida, Takashi Raffeld, Mark TI MDM2 antagonist Nutlin-3 enhances bortezomib-mediated mitochondrial apoptosis in TP53-mutated mantle cell lymphoma SO CANCER LETTERS LA English DT Article DE Mantle cell lymphoma; TP53; MDM2; Bortezomib; Nutlin-3 ID PROTEASOME INHIBITOR BORTEZOMIB; NON-HODGKINS-LYMPHOMA; PHASE-II; DNA-DAMAGE; P53; ACTIVATION; SURVIVAL; NOXA; LINE; ESTABLISHMENT AB This study demonstrated a pronounced synergistic growth-inhibitory effect of an MDM2 inhibitor Nutlin-3 and a proteasome inhibitor bortezomib in mantle cell lymphoma (MCL) cells regardless of TP53 mutant status and innate bortezomib sensitivity. In the mutant TP53 MCL cells which are intrinsically resistant to bortezomib, the combination of Nutlin-3/bortezomib synergistically induced cytotoxicity through the mitochondrial apoptotic pathway mediated by transcription-independent upregulation of NOXA, sequestration of MCL-1, activation of BAX, BAK, caspase-9 and -3. In the bortezomib sensitive wild-type TP53 MCL cells, the Nutlin-3/bortezomib combination caused G0/G1 cell cycle arrest followed by the increase in apoptosis induction. These findings indicate potential therapeutic efficacy of Nutlin-3/bortezomib combination for the treatment of chemorefractory MCL (c) 2010 Elsevier Ireland Ltd. All rights reserved. C1 [Jin, Linhua; Tabe, Yoko; Zhou, Yixin; Miida, Takashi] Juntendo Univ, Sch Med, Dept Clin Pathol, Tokyo 113, Japan. [Kojima, Kensuke] Univ Texas MD Anderson Canc Ctr, Dept Stem Cell Transplantat & Cellular Therapy, Houston, TX 77030 USA. [Konopleva, Marina] Univ Texas MD Anderson Canc Ctr, Dept Leukemia, Houston, TX 77030 USA. [Pittaluga, Stefania; Raffeld, Mark] NCI, Hematopathol Sect, Pathol Lab, Bethesda, MD 20892 USA. RP Tabe, Y (reprint author), Juntendo Univ, Sch Med, Dept Clin Lab Med, 2-1-1 Bunkyo Ku, Tokyo 113, Japan. EM tabe@juntendo.ac.jp RI Miida, Takashi/A-5589-2012 OI Miida, Takashi/0000-0002-4294-8030 FU Japan Science and Technology Agency; Japan Leukemia Research Fund; Osaka Cancer Research Fund; Juntendo University School of Medicine FX This work was supported by Grant-in-Aid for Scientific Research of the Japan Science and Technology Agency, Japan Leukemia Research Fund, and Osaka Cancer Research Fund (to Y.T.), and Project Research Program from Juntendo University School of Medicine (to L.J.). NR 34 TC 25 Z9 25 U1 0 U2 6 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0304-3835 J9 CANCER LETT JI Cancer Lett. PD DEC 28 PY 2010 VL 299 IS 2 BP 161 EP 170 DI 10.1016/j.canlet.2010.08.015 PG 10 WC Oncology SC Oncology GA 690CE UT WOS:000284977000008 PM 20850924 ER PT J AU Neuman, KC AF Neuman, Keir C. TI Evolutionary twist on topoisomerases: Conversion of gyrase to topoisomerase IV SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Editorial Material ID DNA TOPOISOMERASES; II TOPOISOMERASES C1 NHLBI, Lab Mol Biophys, NIH, Bethesda, MD 20892 USA. RP Neuman, KC (reprint author), NHLBI, Lab Mol Biophys, NIH, Bldg 10, Bethesda, MD 20892 USA. EM neumankc@nhlbi.nih.gov RI Neuman, Keir/F-7400-2011 OI Neuman, Keir/0000-0002-0863-5671 FU Intramural NIH HHS NR 14 TC 1 Z9 1 U1 0 U2 9 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 DEC 28 PY 2010 VL 107 IS 52 BP 22363 EP 22364 DI 10.1073/pnas.1016041108 PG 2 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 699SX UT WOS:000285684200005 PM 21169503 ER PT J AU Grundy, GJ Yang, W Gellert, M AF Grundy, Gabrielle J. Yang, Wei Gellert, Martin TI Autoinhibition of DNA cleavage mediated by RAG1 and RAG2 is overcome by an epigenetic signal in V(D)J recombination SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE diversification; immunoglobulin gene; regulation ID POSTCLEAVAGE COMPLEX; PLANT HOMEODOMAIN; C-TERMINUS; IN-VITRO; TRANSPOSITION; EFFICIENT; LYSINE-4; PROTEINS; FINGER; MICE AB Gene assembly of the variable domain of antigen receptors is initiated by DNA cleavage by the RAG1-RAG2 protein complex at sites flanking V, D, and J gene segments. Double-strand breaks are produced via a single-strand nick that is converted to a hairpin end on coding DNA and a blunt end on the neighboring recombination signal sequence. We demonstrate that the C-terminal regions of purified murine RAG1 (aa 1009-1040) and RAG2 (aa 388-520, including a plant homeodomain [PHD domain]) collaborate to inhibit the hairpinning stage of DNA cleavage. The C-terminal region of RAG2 stabilizes the RAG1/2 heterotetramer but destabilizes the RAG-DNA precleavage complex. This destabilization is reversed by binding of the PHD domain to a histone H3 peptide trimethylated on lysine 4 (H3K4me3). The addition of H3K4me3 likewise alleviates the RAG1/RAG2 C-terminus-mediated inhibition of hairpinning and the PHD-mediated inhibition of transposition activity. Thus a negative regulatory function of the noncore regions of RAG1/2 limits the RAG endonuclease activity in the absence of an activating methylated histone tail bound to the complex. C1 [Grundy, Gabrielle J.; Yang, Wei; Gellert, Martin] NIDDK, Mol Biol Lab, NIH, Bethesda, MD 20892 USA. RP Gellert, M (reprint author), NIDDK, Mol Biol Lab, NIH, Bethesda, MD 20892 USA. EM gellert@helix.nih.gov RI Yang, Wei/D-4926-2011 OI Yang, Wei/0000-0002-3591-2195 FU National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health FX This work was supported by the intramural research program of the National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health. NR 24 TC 26 Z9 26 U1 0 U2 2 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 DEC 28 PY 2010 VL 107 IS 52 BP 22487 EP 22492 DI 10.1073/pnas.1014958107 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 699SX UT WOS:000285684200029 PM 21149691 ER PT J AU Ming, M Shea, CR Guo, XM Li, XL Soltani, K Han, WN He, YY AF Ming, Mei Shea, Christopher R. Guo, Xiumei Li, Xiaoling Soltani, Keyoumars Han, Weinong He, Yu-Ying TI Regulation of global genome nucleotide excision repair by SIRT1 through xeroderma pigmentosum C SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE UVB; PTEN; AKT ID UV-INDUCED UBIQUITYLATION; UBIQUITIN LIGASE COMPLEX; DNA-DAMAGE RESPONSE; TUMOR-SUPPRESSOR; LUNG-CANCER; IN-VIVO; MAMMALIAN SIRTUINS; SKIN-CANCER; PROTEIN; XPC AB Disruption of the nucleotide excision repair (NER) pathway by mutations can cause xeroderma pigmentosum, a syndrome predisposing affected individuals to development of skin cancer. The xeroderma pigmentosum C (XPC) protein is essential for initiating global genome NER by recognizing the DNA lesion and recruiting downstream factors. Here we show that inhibition of the deacetylase and longevity factor SIRT1 impairs global genome NER through suppressing the transcription of XPC in a SIRT1 deacetylase-dependent manner. SIRT1 enhances XPC expression by reducing AKT-dependent nuclear localization of the transcription repressor of XPC. Finally, we show that SIRT1 levels are significantly reduced inhuman skin tumors from Caucasian patients, a population at highest risk. These findings suggest that SIRT1 acts as a tumor suppressor through its role in DNA repair. C1 [Ming, Mei; Shea, Christopher R.; Soltani, Keyoumars; Han, Weinong; He, Yu-Ying] Univ Chicago, Dept Med, Dermatol Sect, Chicago, IL 60637 USA. [Guo, Xiumei; Li, Xiaoling] NIEHS, Lab Signal Transduct, NIH, Res Triangle Pk, NC 27709 USA. RP He, YY (reprint author), Univ Chicago, Dept Med, Dermatol Sect, 5841 S Maryland Ave, Chicago, IL 60637 USA. EM yyhe@medicine.bsd.uchicago.edu FU National Institutes of Health (NIH) [ES016936, Z01 ES102205, UL1RR024999]; University of Chicago Comprehensive Cancer Center [P30 CA014599]; University of Chicago FX We thank Terri Li for SIRT1 immunohistochemistry. We are grateful to Dr. Pradip Raychaudhuri (University of Illinois, Chicago) for kindly providing the XPC-Luc plasmids and to Dr. Ann Motten for critical reading of the manuscript. This work was supported by National Institutes of Health (NIH) Grant ES016936 (to Y.Y.H.), NIH Grant Z01 ES102205 (to X. L.), University of Chicago Comprehensive Cancer Center Grant P30 CA014599, Clinical and Translational Science Award NIH Grant UL1RR024999, and the University of Chicago Friends of Dermatology Endowment Fund. NR 69 TC 63 Z9 70 U1 0 U2 10 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD DEC 28 PY 2010 VL 107 IS 52 BP 22623 EP 22628 DI 10.1073/pnas.1010377108 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 699SX UT WOS:000285684200052 PM 21149730 ER PT J AU Tanaka, A Cleland, MM Xu, S Narendra, DP Suen, DF Karbowski, M Youle, RJ AF Tanaka, Atsushi Cleland, Megan M. Xu, Shan Narendra, Derek P. Suen, Der-Fen Karbowski, Mariusz Youle, Richard J. TI Proteasome and p97 mediate mitophagy and degradation of mitofusins induced by Parkin SO JOURNAL OF CELL BIOLOGY LA English DT Article ID REGULATES MITOCHONDRIAL MORPHOLOGY; ENDOPLASMIC-RETICULUM; PROTEOLYTIC CLEAVAGE; PROTEIN-DEGRADATION; PINK1; DISEASE; FUSION; MUTATIONS; DROSOPHILA; FISSION AB Damage to mitochondria can lead to the depolarization of the inner mitochondrial membrane, thereby sensitizing impaired mitochondria for selective elimination by autophagy. However, fusion of uncoupled mitochondria with polarized mitochondria can compensate for damage, reverse membrane depolarization, and obviate mitophagy. Parkin, an E3 ubiquitin ligase that is mutated in monogenic forms of Parkinson's disease, was recently found to induce selective autophagy of damaged mitochondria. Here we show that ubiquitination of mitofusins Mfn1 and Mfn2, large GTPases that mediate mitochondrial fusion, is induced by Parkin upon membrane depolarization and leads to their degradation in a proteasome-and p97-dependent manner. p97, a AAA+ ATPase, accumulates on mitochondria upon uncoupling of Parkin-expressing cells, and both p97 and proteasome activity are required for Parkin-mediated mitophagy. After mitochondrial fission upon depolarization, Parkin prevents or delays refusion of mitochondria, likely by the elimination of mitofusins. Inhibition of Drp1-mediated mitochondrial fission, the proteasome, or p97 prevents Parkin-induced mitophagy. C1 [Tanaka, Atsushi; Cleland, Megan M.; Narendra, Derek P.; Suen, Der-Fen; Youle, Richard J.] NINDS, Biochem Sect, Surg Neurol Branch, NIH, Bethesda, MD 20892 USA. [Xu, Shan; Karbowski, Mariusz] Univ Maryland, Ctr Biomed Engn & Technol, Baltimore, MD 21201 USA. [Xu, Shan; Karbowski, Mariusz] Univ Maryland, Dept Biochem & Mol Biol, Sch Med, Baltimore, MD 21201 USA. RP Youle, RJ (reprint author), NINDS, Biochem Sect, Surg Neurol Branch, NIH, Bethesda, MD 20892 USA. EM mkarbowski@umaryland.edu; youler@ninds.nih.gov RI Xu, Shan/F-7268-2014; OI Harwig, Megan/0000-0003-2140-5739 FU National Institute of Neurological Disorders and Stroke; National Institute of General Medical Sciences [R01: GM083131]; Japan Society for the Promotion of Science FX This work is supported by the National Institute of Neurological Disorders and Stroke intramural program (to R.J. Youle), the National Institute of General Medical Sciences (to M. Karbowski; R01: GM083131), and the Japan Society for the Promotion of Science fellowship (to A. Tanaka). NR 57 TC 477 Z9 487 U1 6 U2 48 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 1114 FIRST AVE, 4TH FL, NEW YORK, NY 10021 USA SN 0021-9525 J9 J CELL BIOL JI J. Cell Biol. PD DEC 27 PY 2010 VL 191 IS 7 BP 1367 EP 1380 DI 10.1083/jcb.201007013 PG 14 WC Cell Biology SC Cell Biology GA 699SR UT WOS:000285683600014 PM 21173115 ER PT J AU Chen, SR Chen, H Yuan, WX Wess, J Pan, HL AF Chen, Shao-Rui Chen, Hong Yuan, Wei-Xiu Wess, Juergen Pan, Hui-Lin TI Dynamic Control of Glutamatergic Synaptic Input in the Spinal Cord by Muscarinic Receptor Subtypes Defined Using Knockout Mice SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID DORSAL-HORN NEURONS; ACETYLCHOLINE-RECEPTOR; CHOLINERGIC RECEPTORS; AUTORADIOGRAPHIC LOCALIZATION; PROJECTION NEURONS; GABA(B) RECEPTORS; GLYCINERGIC INPUT; NEUROPATHIC PAIN; GABAERGIC INPUTS; TRANSMISSION AB Activation of muscarinic acetylcholine receptors (mAChRs) in the spinal cord inhibits pain transmission. At least three mAChR subtypes (M-2, M-3, andM(4)) are present in the spinal dorsal horn. However, it is not clear how each mAChR subtype contributes to the regulation of glutamatergic input to dorsal horn neurons. We recorded spontaneous excitatory postsynaptic currents (sEPSCs) from lamina II neurons in spinal cord slices from wild-type (WT) and mAChR subtype knock-out (KO) mice. The mAChR agonist oxotremorine-M increased the frequency of glutamatergic sEPSCs in 68.2% neurons from WT mice and decreased the sEPSC frequency in 21.2% neurons. Oxotremorine-M also increased the sEPSC frequency in similar to 50% neurons fromM(3)-single KO andM(1)/M-3 double-KO mice. In addition, the M-3 antagonist J104129 did not block the stimulatory effect of oxotremorine-M in the majority of neurons from WT mice. Strikingly, in M-5-single KO mice, oxotremorine-M increased sEPSCs in only 26.3% neurons, and J104129 abolished this effect. InM2/M-4 double-KO mice, but not M-2-or M-4-single KO mice, oxotremorine-M inhibited sEPSCs in significantly fewer neurons compared with WT mice, and blocking group II/III metabotropic glutamate receptors abolished this effect. The M-2/M-4 antagonist himbacine either attenuated the inhibitory effect of oxotremorine-M or potentiated the stimulatory effect of oxotremorine-M in WT mice. Our study demonstrates that activation of the M-2 and M-4 receptor subtypes inhibits synaptic glutamate release to dorsal horn neurons. M-5 is the predominant receptor subtype that potentiates glutamatergic synaptic transmission in the spinal cord. C1 [Chen, Shao-Rui] Univ Texas MD Anderson Canc Ctr, Dept Anesthesiol & Perioperat Med, Unit 110, Houston, TX 77030 USA. [Wess, Juergen] NIDDK, Bioorgan Chem Lab, NIH, Bethesda, MD 20892 USA. RP Chen, SR (reprint author), Univ Texas MD Anderson Canc Ctr, Dept Anesthesiol & Perioperat Med, Unit 110, 1515 Holcombe Blvd, Houston, TX 77030 USA. EM schen@mdanderson.org FU National Institutes of Health [GM64830, NS45602]; N.G. and Helen T. Hawkins endowment FX This work was supported, in whole or in part, by Grants GM64830 and NS45602 from the National Institutes of Health and by the N.G. and Helen T. Hawkins endowment (to H.-L. P.). NR 44 TC 5 Z9 5 U1 0 U2 3 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD DEC 24 PY 2010 VL 285 IS 52 BP 40427 EP 40437 DI 10.1074/jbc.M110.176966 PG 11 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 696AN UT WOS:000285414400005 PM 20940295 ER PT J AU Prasad, R Shock, DD Beard, WA Wilson, SH AF Prasad, Rajendra Shock, David D. Beard, William A. Wilson, Samuel H. TI Substrate Channeling in Mammalian Base Excision Repair Pathways: Passing the Baton SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID DNA-POLYMERASE-BETA; DEOXYRIBOSE PHOSPHATE LYASE; LIGASE-I; BOVINE TESTIS; IDENTIFICATION; MECHANISM; CELLS; RECONSTITUTION; BINDING; PROTEIN AB The current model for base excision repair (BER) involves two general sub-pathways termed single-nucleotide BER and long patch BER that are distinguished by their repair patch sizes and the enzymes/co-factors involved. Both sub-pathways involve a series of sequential steps from initiation to completion of repair. The BER sub-pathways are designed to sequester the various intermediates, passing them along from one step to the next without allowing these toxic molecules to trigger cell cycle arrest, necrotic cell death, or apoptosis. Although a variety of DNA-protein and protein-protein interactions are known for the BER intermediates and enzymes/co-factors, the molecular mechanisms accounting for step-to-step coordination are not well understood. In the present study we designed an in vitro assay to explore the question of whether there is a channeling or "hand-off" of the repair intermediates during BER in vitro. The results show that when BER enzymes are pre-bound to the initial single-nucleotide BER intermediate, the DNA is channeled from apurinic/apyrimidinic endonuclease 1 to DNA polymerase beta and then to DNA ligase. In the long patch BER subpathway, where the 5'-end of the incised strand is blocked, the intermediate after DNA polymerase beta gap filling is not channeled to the subsequent enzyme, flap endonuclease 1. Instead, flap endonuclease 1 must recognize and bind to the intermediate in competition with other molecules. C1 [Prasad, Rajendra; Shock, David D.; Beard, William A.; Wilson, Samuel H.] NIEHS, Struct Biol Lab, NIH, Res Triangle Pk, NC 27709 USA. RP Wilson, SH (reprint author), 111 TW Alexander Dr, Res Triangle Pk, NC 27709 USA. EM wilson5@niehs.nih.gov FU National Institutes of Health Research [Z01-ES050158, Z01-ES050159]; NIEHS FX This work was supported, in whole or in part, by National Institutes of Health Research Projects Z01-ES050158 and Z01-ES050159 in the Intramural Research Program of the NIEHS. NR 44 TC 52 Z9 52 U1 0 U2 1 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD DEC 24 PY 2010 VL 285 IS 52 BP 40479 EP 40488 DI 10.1074/jbc.M110.155267 PG 10 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 696AN UT WOS:000285414400010 PM 20952393 ER PT J AU Noh, OJ Park, YH Chung, YW Kim, IY AF Noh, Ok Jeong Park, Yong Hwan Chung, Youn Wook Kim, Ick Young TI Transcriptional Regulation of Selenoprotein W by MyoD during Early Skeletal Muscle Differentiation SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID MYOGENIC DIFFERENTIATION; OXIDATIVE STRESS; BINDING PROTEIN; MYOBLAST CELLS; DNA-BINDING; STEM-CELLS; EXPRESSION; GENE; THIOREDOXIN; ACTIVATION AB Selenoprotein W (SelW) is expressed in various tissues, but it is especially high in the skeletal muscle of mammals. Such tissue-specific protein expression implies regulation by a tissue-specific factor. In this study, we investigated SelW expression during myogenic C2C12 cell differentiation using RTPCR, quantitative PCR, and Western blot analysis. Both the protein and mRNA levels of SelW were increased during C2C12 cell differentiation, particularly during the early stage. Sequence analysis of the SelW promoter revealed four putative E-boxes, E1, E2, E3, and E4, which are known binding sites for MyoD, a myogenic transcriptional factor. Luciferase reporter assay showed that E1 and E4 were crucial for MyoD-dependent promoter activity. Using EMSA analysis, we observed that MyoD bound directly to E1 but not to E4, even though E4 mutation reduced SelW promoter activity in the luciferase reporter assay. Binding of MyoD to E1 was further investigated by ChIP assay. These results suggest that the SelW gene was activated by the binding of MyoD to a specific E-box during early skeletal muscle differentiation. C1 [Noh, Ok Jeong; Park, Yong Hwan; Kim, Ick Young] Korea Univ, Lab Cellular & Mol Biochem, Sch Life Sci & Biotechnol, Seoul 136701, South Korea. [Chung, Youn Wook] NHLBI, Biochem Lab, NIH, Bethesda, MD 20892 USA. RP Kim, IY (reprint author), Korea Univ, Lab Cellular & Mol Biochem, Sch Life Sci & Biotechnol, Seoul 136701, South Korea. EM ickkim@korea.ac.kr FU Korean Government (MOEHRD) [KRF-2005-070-C00086]; Korea University FX This work was authored, in whole or in part, by National Institutes of Health staff. This work was funded by Korea Research Foundation Grant from the Korean Government (MOEHRD) KRF-2005-070-C00086 (to I. Y. K.) and in part by a Korea University grant. NR 41 TC 14 Z9 14 U1 1 U2 10 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD DEC 24 PY 2010 VL 285 IS 52 BP 40496 EP 40507 DI 10.1074/jbc.M110.152934 PG 12 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 696AN UT WOS:000285414400012 PM 20956524 ER PT J AU Park, H Boyington, JC AF Park, HaJeung Boyington, Jeffrey C. TI The 1.5 angstrom Crystal Structure of Human Receptor for Advanced Glycation Endproducts (RAGE) Ectodomains Reveals Unique Features Determining Ligand Binding SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID END-PRODUCTS RAGE; CELL-SURFACE RECEPTOR; PATTERN-RECOGNITION; SCAVENGER RECEPTORS; ALZHEIMERS-DISEASE; NMR SYSTEM; PROTEINS; ACTIVATION; S100B; CRYSTALLOGRAPHY AB Interaction of the pattern recognition receptor, RAGE with key ligands such as advanced glycation end products (AGE), S100 proteins, amyloid beta, and HMGB1 has been linked to diabetic complications, inflammatory and neurodegenerative disorders, and cancer. To help answer the question of how a single receptor can recognize and respond to a diverse set of ligands we have investigated the structure and binding properties of the first two extracellular domains of human RAGE, which are implicated in various ligand binding and subsequent signaling events. The 1.5-angstrom crystal structure reveals an elongated molecule with a large basic patch and a large hydrophobic patch, both highly conserved. Isothermal titration calorimetry (ITC) and deletion experiments indicate S100B recognition by RAGE is an entropically driven process involving hydrophobic interaction that is dependent on Ca2+ and on residues in the C'D loop (residues 54-67) of domain 1. In contrast, competition experiments using gel shift assays suggest that RAGE interaction with AGE is driven by the recognition of negative charges on AGE-proteins. We also demonstrate that RAGE can bind to dsDNA and dsRNA. These findings reveal versatile structural features of RAGE that help explain its ability to recognize of multiple ligands. C1 [Park, HaJeung; Boyington, Jeffrey C.] NIEHS, Struct Biol Lab, NIH, Res Triangle Pk, NC 27709 USA. RP Park, H (reprint author), Scripps Res Inst, Jupiter, FL 33458 USA. EM hajpark@scripps.edu; boyingtonj@niaid.nih.gov FU National Institutes of Health, NIEHS FX This work was supported, in whole or in part, by the Intramural Research Program of the National Institutes of Health, NIEHS. NR 49 TC 55 Z9 59 U1 0 U2 10 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD DEC 24 PY 2010 VL 285 IS 52 BP 40762 EP 40770 DI 10.1074/jbc.M110.169276 PG 9 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 696AN UT WOS:000285414400040 PM 20943659 ER PT J AU Kohli, RM Maul, RW Guminski, AF McClure, RL Gajula, KS Saribasak, H McMahon, MA Siliciano, RF Gearhart, PJ Stivers, JT AF Kohli, Rahul M. Maul, Robert W. Guminski, Amy F. McClure, Rhonda L. Gajula, Kiran S. Saribasak, Huseyin McMahon, Moira A. Siliciano, Robert F. Gearhart, Patricia J. Stivers, James T. TI Local Sequence Targeting in the AID/APOBEC Family Differentially Impacts Retroviral Restriction and Antibody Diversification SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID IMMUNODEFICIENCY-VIRUS TYPE-1; INDUCED CYTIDINE DEAMINASE; CLASS SWITCH RECOMBINATION; SOMATIC HYPERMUTATION; HUMAN APOBEC3G; HIV-1 INFECTION; DNA INTEGRATION; IN-VIVO; AID; CELLS AB Nucleic acid cytidine deaminases of the activation-induced deaminase (AID)/APOBEC family are critical players in active and innate immune responses, playing roles as target-directed, purposeful mutators. AID specifically deaminates the host immunoglobulin (Ig) locus to evolve antibody specificity, whereas its close relative, APOBEC3G (A3G), lethally mutates the genomes of retroviral pathogens such as HIV. Understanding the basis for the target-specific action of these enzymes is essential, as mistargeting poses significant risks, potentially promoting oncogenesis (AID) or fostering drug resistance (A3G). AID prefers to deaminate cytosine in WRC (W = A/T, R = A/G) motifs, whereas A3G favors deamination of CCC motifs. This specificity is largely dictated by a single, divergent protein loop in the enzyme family that recognizes the DNA sequence. Through grafting of this substrate-recognition loop, we have created enzyme variants of A3G and AID with altered local targeting to directly evaluate the role of sequence specificity on immune function. We find that grafted loops placed in the A3G scaffold all produced efficient restriction of HIV but that foreign loops in the AID scaffold compromised hypermutation and class switch recombination. Local targeting, therefore, appears alterable for innate defense against retroviruses by A3G but important for adaptive antibody maturation catalyzed by AID. Notably, AID targeting within the Ig locus is proportionally correlated to its in vitro ability to target WRC sequences rather than non-WRC sequences. Although other mechanisms may also contribute, our results suggest that local sequence targeting by AID/APOBEC3 enzymes represents an elegant example of co-evolution of enzyme specificity with its target DNA sequence. C1 [Maul, Robert W.; McClure, Rhonda L.; Saribasak, Huseyin; Gearhart, Patricia J.] NIA, Lab Mol Gerontol, NIH, Baltimore, MD 21224 USA. [Kohli, Rahul M.; Gajula, Kiran S.; Siliciano, Robert F.] Johns Hopkins Univ, Sch Med, Dept Med, Baltimore, MD 21205 USA. [Guminski, Amy F.; McMahon, Moira A.; Stivers, James T.] Johns Hopkins Univ, Sch Med, Dept Pharmacol & Mol Sci, Baltimore, MD 21205 USA. RP Gearhart, PJ (reprint author), NIA, Lab Mol Gerontol, NIH, 251 Bayview Blvd, Baltimore, MD 21224 USA. EM gearhartp@mail.nih.gov; jstivers@jhmi.edu RI Saribasak, Huseyin/C-9331-2012; OI Saribasak, Huseyin/0000-0003-0055-062X; Maul, Robert/0000-0002-6958-8514; Kohli, Rahul/0000-0002-7689-5678 FU NIA; National Institutes of Health; [GM06669]; [GM056834]; [KAI089242A] FX This work was supported, in whole or in part, by NIA, National Institutes of Health (Intramural Research Program), T32 Grant GM06669, and Grants GM056834 (to J. T. S.) and KAI089242A (to R. M. K.). NR 53 TC 32 Z9 32 U1 1 U2 6 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD DEC 24 PY 2010 VL 285 IS 52 BP 40956 EP 40964 DI 10.1074/jbc.M110.177402 PG 9 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 696AN UT WOS:000285414400059 PM 20929867 ER PT J AU Jain, S Tillinger, A Mopidevi, B Pandey, VG Chauhan, CK Fiering, SN Warming, S Kumar, A AF Jain, Sudhir Tillinger, Andrej Mopidevi, Brahmaraju Pandey, Varunkumar G. Chauhan, Chetankumar K. Fiering, Steven N. Warming, Soren Kumar, Ashok TI Transgenic Mice with -6A Haplotype of the Human Angiotensinogen Gene Have Increased Blood Pressure Compared with -6G Haplotype SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID GENOME-WIDE ASSOCIATION; PHOSPHOENOLPYRUVATE CARBOXYKINASE; ESSENTIAL-HYPERTENSION; MOLECULAR-GENETICS; PROMOTER ACTIVITY; HUMAN RENIN; C/EBP BETA; EXPRESSION; TRANSCRIPTION; RAT AB Hypertension is a serious risk factor for cardiovascular disease, and the angiotensinogen (AGT) gene locus is associated with human essential hypertension. The human AGT (hAGT) gene has an A/G polymorphism at -6, and the -6A allele is associated with increased blood pressure. However, transgenic mice containing 1.2 kb of the promoter with -6A of the hAGT gene show neither increased plasma AGT level nor increased blood pressure compared with -6G. We have found that the hAGT gene has three additional SNPs (A/G at -1670, C/G at -1562, and T/G at -1561). Variants -1670A, -1562C, and -1561T almost always occur with -6A, and variants -1670G, -1562G, and -1561G almost always occur with -6G. Therefore, the hAGT gene may be subdivided into either -6A or -6G haplotypes. We show that these polymorphisms affect the binding of HNF-1 alpha and glucocorticoid receptor to the promoter, and a reporter construct containing a 1.8-kb hAGT gene promoter with -6A haplotype has 4-fold increased glucocorticoid-induced promoter activity as compared with -6G haplotype. In order to understand the physiological significance of these haplotypes in an in vivo situation, we have generated double transgenic mice containing either the -6A or -6G haplotype of the hAGT gene and the human renin gene. Our ChIP assay shows that HNF-1 alpha and glucocorticoid receptor have stronger affinity for the chromatin obtained from the liver of transgenic mice containing -6A haplotype. Our studies also show that transgenic mice containing -6A haplotype have increased plasma AGT level and increased blood pressure as compared with -6G haplotype. Our studies explain the molecular mechanism involved in association of the -6A allele of the hAGT gene with hypertension. C1 [Jain, Sudhir; Tillinger, Andrej; Mopidevi, Brahmaraju; Pandey, Varunkumar G.; Chauhan, Chetankumar K.; Kumar, Ashok] New York Med Coll, Dept Pathol, Valhalla, NY 10595 USA. [Fiering, Steven N.] Dartmouth Med Sch, Dept Microbiol Immunol & Genet, Hanover, NH 03755 USA. [Warming, Soren] NCI Frederick, Mouse Canc Genet Program, NIH, Frederick, MD 21702 USA. RP Kumar, A (reprint author), New York Med Coll, Dept Pathol, Rm 455,Basic Sci Bldg, Valhalla, NY 10595 USA. EM ashok_kumar@nymc.edu RI Mopidevi, Brahmaraju/D-6003-2015 FU National Institutes of Health [HL081752, HL66296] FX This work was supported, in whole or in part, by National Institutes of Health Grants HL081752 and HL66296 (to A. K.). NR 52 TC 9 Z9 9 U1 0 U2 0 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD DEC 24 PY 2010 VL 285 IS 52 BP 41172 EP 41186 DI 10.1074/jbc.M110.167585 PG 15 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 696AN UT WOS:000285414400079 PM 20978123 ER PT J AU Chen, J Petrus, M Bryant, BR Nguyen, VP Goldman, CK Bamford, R Morris, JC Janik, JE Waldmann, TA AF Chen, Jing Petrus, Mike Bryant, Bonita R. Nguyen, Vinh Phuc Goldman, Carolyn K. Bamford, Richard Morris, John C. Janik, John E. Waldmann, Thomas A. TI Autocrine/paracrine cytokine stimulation of leukemic cell proliferation in smoldering and chronic adult T-cell leukemia SO BLOOD LA English DT Article ID VIRUS TYPE-I; KAPPA-B SITE; HTLV-I; GENE-EXPRESSION; TAX PROTEIN; DOWN-REGULATION; INTERLEUKIN-2; PROGRESSION; LYMPHOMA; CLONES AB Adult T-cell leukemia (ATL), a heterogeneous disease, can be divided into smoldering, chronic, lymphoma, and acute types clinically. In addition to different clinical manifestations, different stages of ATL have different molecular signatures. Here, we demonstrated that smoldering/chronic ATL peripheral blood mononuclear cells spontaneously proliferated ex vivo in a cytokine (interleukin -12 [IL-12]/IL-9/IL-15)-dependent manner, while acute-type ATL peripheral blood mononuclear cells did not proliferate or proliferated independent of cytokines. Smoldering/chronic ATL cells produced IL-2 and IL-9 in 6-day ex vivo cultures. Interestingly, the addition of an anti-IL-2R-alpha monoclonal antibody profoundly inhibited IL-9 expression, suggesting optimal expression of IL-9 was dependent on IL-2 signaling in these patients. To determine whether there would be autonomous proliferation of ATL leukemic cells, we purified leukemic cells from patients with smoldering/chronic ATL. Purified leukemic cells cultured alone produced IL-2/IL-9, and the downstream Janus kinase/signal transducer and activator of transcription pathway was activated. However, the leukemic cells did not proliferate independently, but required coculture with autologous monocytes to induce proliferation. Moreover, interaction between leukemic cells and monocytes was contact dependent, and major histocompatibility complex class II expression may have contributed to this interaction. In conclusion, our data provide evidence that there is autocrine/paracrine cytokine stimulation of leukemic cell proliferation in patients with smoldering/chronic ATL that could be targeted for treatment. (Blood. 2010;116(26):5948-5956) C1 [Waldmann, Thomas A.] NCI, Metab Branch, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. RP Waldmann, TA (reprint author), NCI, Metab Branch, Ctr Canc Res, NIH, Bldg 10,Rm 4N115,10 Ctr Dr, Bethesda, MD 20892 USA. EM tawald@helix.nih.gov FU National Cancer Institute, National Institutes of Health FX This study was supported by the intramural research program of the National Cancer Institute, National Institutes of Health. NR 37 TC 14 Z9 14 U1 2 U2 5 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD DEC 23 PY 2010 VL 116 IS 26 BP 5948 EP 5956 DI 10.1182/blood-2010-04-277418 PG 9 WC Hematology SC Hematology GA 698GX UT WOS:000285583400025 PM 20858854 ER PT J AU Kovtunovych, G Eckhaus, MA Ghosh, MC Ollivierre-Wilson, H Rouault, TA AF Kovtunovych, Gennadiy Eckhaus, Michael A. Ghosh, Manik C. Ollivierre-Wilson, Hayden Rouault, Tracey A. TI Dysfunction of the heme recycling system in heme oxygenase 1-deficient mice: effects on macrophage viability and tissue iron distribution SO BLOOD LA English DT Article ID RECEPTOR-MEDIATED UPTAKE; SCAVENGER RECEPTOR; HEMOPEXIN; DEFICIENCY; HEMOGLOBIN; PROTEIN; LIVER; TRANSPORT; DISEASE; CELL AB To better understand the tissue iron overload and anemia previously reported in a human patient and mice that lack heme oxygenase-1 (HO-1), we studied iron distribution and pathology in HO-1(Hmox1)(-/-) mice. We found that resident splenic and liver macrophages were mostly absent in HO-1(-/-) mice. Erythrophagocytosis caused the death of HO-1(-/-) macrophages in in vitro experiments, supporting the hypothesis that HO-1(-/-) macrophages died of exposure to heme released on erythrophagocytosis. Rupture of HO-1(-/-) macro-phages in vivo and release of nonmetabolized heme probably caused tissue inflammation. In the spleen, initial splenic enlargement progressed to red pulp fibrosis, atrophy, and functional hyposplenism in older mice, recapitulating the asplenia of an HO-1-deficient patient. We postulate that the failure of tissue macrophages to remove senescent erythrocytes led to intravascular hemolysis and increased expression of the heme and hemoglobin scavenger proteins, hemopexin and haptoglobin. Lack of macro-phages expressing the haptoglobin receptor, CD163, diminished the ability of haptoglobin to neutralize circulating hemoglobin, and iron overload occurred in kidney proximal tubules, which were able to catabolize heme with HO-2. Thus, in HO-1(-/-) mammals, the reduced function and viability of erythrophagocytosing macrophages are the main causes of tissue damage and iron redistribution. (Blood. 2010; 116(26):6054-6062) C1 [Kovtunovych, Gennadiy; Ghosh, Manik C.; Ollivierre-Wilson, Hayden; Rouault, Tracey A.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Program Mol Med, Bethesda, MD 20892 USA. [Eckhaus, Michael A.] NIH, Div Vet Resources, Off Res Serv, Off Director, Bethesda, MD 20892 USA. RP Rouault, TA (reprint author), Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Program Mol Med, 9000 Rockville Pike,Bldg 18T,Rm 101, Bethesda, MD 20892 USA. EM trou@helix.nih.gov FU National Institute of Child Health and Human Development FX This work was supported by the National Institute of Child Health and Human Development (intramural program). NR 37 TC 82 Z9 84 U1 0 U2 4 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD DEC 23 PY 2010 VL 116 IS 26 BP 6054 EP 6062 DI 10.1182/blood-2010-03-272138 PG 9 WC Hematology SC Hematology GA 698GX UT WOS:000285583400037 PM 20844238 ER PT J AU Johnson, ST Newton, AS Chopra, M Buckingham, J Huang, TTK Franks, PW Jetha, MM Ball, GDC AF Johnson, Steven T. Newton, Amanda S. Chopra, Meera Buckingham, Jeanette Huang, Terry T. K. Franks, Paul W. Jetha, Mary M. Ball, Geoff D. C. TI In search of quality evidence for lifestyle management and glycemic control in children and adolescents with type 2 diabetes: A systematic review SO BMC PEDIATRICS LA English DT Review ID IMPAIRED GLUCOSE-TOLERANCE; FOLLOW-UP; YOUTH; MELLITUS; PREVALENCE; EPIDEMIC; OBESITY; HEALTH; YOUNG; INTERVENTIONS AB Background: Our purpose was to evaluate the impact of lifestyle behavior modification on glycemic control among children and youth with clinically defined Type 2 Diabetes (T2D). Methods: We conducted a systematic review of studies (randomized trials, quasi-experimental studies) evaluating lifestyle (diet and/or physical activity) modification and glycemic control (HbA1c). Our data sources included bibliographic databases (EMBASE, CINAHL (R), Cochrane Library, Medline (R), PASCAL, PsycINFO (R), and Sociological Abstracts), manual reference search, and contact with study authors. Two reviewers independently selected studies that included any intervention targeting diet and/or physical activity alone or in combination as a means to reduce HbA1c in children and youth under the age of 18 with T2D. Results: Our search strategy generated 4,572 citations. The majority of citations were not relevant to the study objective. One study met inclusion criteria. In this retrospective study, morbidly obese youth with T2D were treated with a very low carbohydrate diet. This single study received a quality index score of < 11, indicating poor study quality and thus limiting confidence in the study's conclusions. Conclusions: There is no high quality evidence to suggest lifestyle modification improves either short- or long-term glycemic control in children and youth with T2D. Additional research is clearly warranted to define optimal lifestyle behaviour strategies for young people with T2D. C1 [Newton, Amanda S.; Jetha, Mary M.; Ball, Geoff D. C.] Univ Alberta, Dept Pediat, Aberhart Ctr 8213, Edmonton, AB T6G 2P3, Canada. [Johnson, Steven T.] Athabasca Univ, Ctr Nursing & Hlth Studies, Fac Hlth Disciplines, Athabasca, AB, Canada. [Chopra, Meera] Mt Sinai Hosp, Toronto, ON M5T 3L9, Canada. [Buckingham, Jeanette] Univ Alberta, John W Scott Hlth Sci Lib, Edmonton, AB T6G 2R7, Canada. [Huang, Terry T. K.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Bethesda, MD USA. [Franks, Paul W.] Umea Univ Hosp, Genet Epidemiol & Clin Res Grp, Dept Publ Hlth & Clin Med, Div Med, S-90185 Umea, Sweden. RP Ball, GDC (reprint author), Univ Alberta, Dept Pediat, Aberhart Ctr 8213, 11402 Univ Ave, Edmonton, AB T6G 2P3, Canada. EM geoff.ball@ualberta.ca OI Franks, Paul/0000-0002-0520-7604 FU V sterbotten's Health Authority; Swedish Heart-Lung Foundation [20070633]; Swedish Diabetes Association [DIA2006-013]; Canadian Institutes of Health Research [CIHR]; Alberta Innovates - Health Solutions FX STJ, MC, JB, and TT-KH received no external support. PWF is supported by V sterbotten's Health Authority (ALF strategic appointment 2006-2009), the Swedish Heart-Lung Foundation (20070633), and the Swedish Diabetes Association (DIA2006-013). ASN is supported by a Career Development Award from the Canadian Child Health Clinician Scientist Program (funded by the Canadian Institutes of Health Research [CIHR]). GDCB is supported by a Population Health Investigator Award from Alberta Innovates - Health Solutions and a New Investigator Award from CIHR. These study sponsors did not play any role in this research or in the decision to submit the paper for publication. Contents of the publication do not necessarily represent the views or policies of the National Institutes of Health. NR 44 TC 11 Z9 11 U1 0 U2 13 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1471-2431 J9 BMC PEDIATR JI BMC Pediatr. PD DEC 23 PY 2010 VL 10 AR 97 DI 10.1186/1471-2431-10-97 PG 8 WC Pediatrics SC Pediatrics GA 703HR UT WOS:000285969500001 PM 21182791 ER PT J AU Kiselev, E Dexheimer, TS Pommier, Y Cushman, M AF Kiselev, Evgeny Dexheimer, Thomas S. Pommier, Yves Cushman, Mark TI Design, Synthesis, and Evaluation of Dibenzo[c,h][1,6]naphthyridines as Topoisomerase I Inhibitors and Potential Anticancer Agents SO JOURNAL OF MEDICINAL CHEMISTRY LA English DT Article ID DNA TOPOISOMERASES; DRUG; CAMPTOTHECIN; CYTOTOXICITY; OPTIMIZATION; HETEROCYCLES; COMPLEXES; COVALENT; NITROGEN; CHLORIDE AB Indenoisoquinoline topoisomerase I (Top 1) inhibitors are a novel class of anticancer agents. Modifications of the indenoisoquinoline A, B, and D rings have been extensively studied in order to optimize Top 1 inhibitory activity and cytotoxicity. To improve understanding of the forces that stabilize drug-Top1-DNA ternary complexes, the five-membered cyclopentadienone C-ring of the indenoisoquinoline system was replaced by six-membered nitrogen heterocyclic rings, resulting in dibenzo[c,h][1,6]naphthyridines that were synthesized by a novel route and tested for Top 1 inhibition. This resulted in several compounds that have unique DNA cleavage site selectivities and potent antitumor activities in a number of cancer cell lines. C1 [Kiselev, Evgeny; Cushman, Mark] Purdue Univ, Dept Med Chem & Mol Pharmacol, Sch Pharm, W Lafayette, IN 47907 USA. [Kiselev, Evgeny; Cushman, Mark] Purdue Univ, Purdue Ctr Canc Res, W Lafayette, IN 47907 USA. [Dexheimer, Thomas S.; Pommier, Yves] NCI, Mol Pharmacol Lab, Ctr Canc Res, Bethesda, MD 20892 USA. RP Cushman, M (reprint author), Purdue Univ, Dept Med Chem & Mol Pharmacol, Sch Pharm, W Lafayette, IN 47907 USA. EM cushman@purdue.edu FU NIH, Center for Cancer Research, National Cancer Institute; National Institute of Health (NIH) [UO1 CA89566] FX TD and YP are supported by the NIH Intramural Program, Center for Cancer Research, National Cancer Institute. This work was made possible by the National Institute of Health (NIH) through support of this work with Research Grant UO1 CA89566. NR 39 TC 32 Z9 32 U1 0 U2 10 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0022-2623 J9 J MED CHEM JI J. Med. Chem. PD DEC 23 PY 2010 VL 53 IS 24 BP 8716 EP 8726 DI 10.1021/jm101048k PG 11 WC Chemistry, Medicinal SC Pharmacology & Pharmacy GA 693ZQ UT WOS:000285264300024 PM 21090809 ER PT J AU Sa, JM Twu, O AF Sa, Juliana M. Twu, Olivia TI Protecting the malaria drug arsenal: halting the rise and spread of amodiaquine resistance by monitoring the PfCRT SVMNT type SO MALARIA JOURNAL LA English DT Editorial Material ID PLASMODIUM-FALCIPARUM MALARIA; CHLOROQUINE-RESISTANCE; CESSATION; TANZANIA; EFFICACY; MALAWI; GENE AB The loss of chloroquine due to selection and spread of drug resistant Plasmodium falciparum parasites has greatly impacted malaria control, especially in highly endemic areas of Africa. Since chloroquine removal a decade ago, the guidelines to treat falciparum malaria suggest combination therapies, preferentially with an artemisinin derivative. One of the recommended partner drugs is amodiaquine, a pro-drug that relies on its active metabolite monodesethylamodiaquine, and is still effective in areas of Africa, but not in regions of South America. Genetic studies on P. falciparum parasites have shown that different pfcrt mutant haplotypes are linked to distinct levels of chloroquine and amodiaquine responses. The pfcrt haplotype SVMNT (termed after the amino acids from codon positions 72-76) is stably present in several areas where amodiaquine was introduced and widely used. Parasites with this haplotype are highly resistant to monodesethylamodiaquine and also resistant to chloroquine. The presence of this haplotype in Africa was found for the first time in 2004 in Tanzania and a role for amodiaquine in the selection of this haplotype was suggested. This commentary discusses the finding of a second site in Africa with high incidence of this haplotype. The >50% SVMNT haplotype prevalence in Angola represents a threat to the rise and spread of amodiaquine resistance. It is paramount to monitor pfcrt haplotypes in every country currently using amodiaquine and to re-evaluate current combination therapies in areas where SVMNT type parasites are prevalent. C1 [Sa, Juliana M.] NIAID, Lab Malaria & Vector Res, NIH, Rockville, MD 20852 USA. [Twu, Olivia] Univ Calif Los Angeles, Dept Microbiol Immunol & Mol Genet, Los Angeles, CA 90095 USA. RP Sa, JM (reprint author), NIAID, Lab Malaria & Vector Res, NIH, 12735 Twinbrook Pkwy,Room 3E-10C, Rockville, MD 20852 USA. EM jsa@niaid.nih.gov OI Twu, Olivia/0000-0002-5175-3016 FU Intramural NIH HHS NR 13 TC 29 Z9 30 U1 0 U2 0 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 DEC 23 PY 2010 VL 9 AR 374 DI 10.1186/1475-2875-9-374 PG 3 WC Infectious Diseases; Parasitology; Tropical Medicine SC Infectious Diseases; Parasitology; Tropical Medicine GA 724VS UT WOS:000287604900003 PM 21182787 ER PT J AU Bevilacqua, L Doly, S Kaprio, J Yuan, QP Tikkanen, R Paunio, T Zhou, ZF Wedenoja, J Maroteaux, L Diaz, S Belmer, A Hodgkinson, CA Dell'Osso, L Suvisaari, J Coccaro, E Rose, RJ Peltonen, L Virkkunen, M Goldman, D AF Bevilacqua, Laura Doly, Stephane Kaprio, Jaakko Yuan, Qiaoping Tikkanen, Roope Paunio, Tiina Zhou, Zhifeng Wedenoja, Juho Maroteaux, Luc Diaz, Silvina Belmer, Arnaud Hodgkinson, Colin A. Dell'Osso, Liliana Suvisaari, Jaana Coccaro, Emil Rose, Richard J. Peltonen, Leena Virkkunen, Matti Goldman, David TI A population-specific HTR2B stop codon predisposes to severe impulsivity SO NATURE LA English DT Article ID ATTENTION-DEFICIT/HYPERACTIVITY DISORDER; MONOAMINE-OXIDASE; MOLECULAR-GENETICS; MALE-MICE; SEROTONIN; BEHAVIOR; VULNERABILITY; PREDICTS; DOPAMINE; MUTATION AB Impulsivity, describing action without foresight, is an important feature of several psychiatric diseases, suicidality and violent behaviour. The complex origins of impulsivity hinder identification of the genes influencing it and the diseases with which it is associated. Here we perform exon-focused sequencing of impulsive individuals in a founder population, targeting fourteen genes belonging to the serotonin and dopamine domain. A stop codon in HTR2B was identified that is common (minor allele frequency >1%) but exclusive to Finnish people. Expression of the gene in the human brain was assessed, as well as the molecular functionality of the stop codon, which was associated with psychiatric diseases marked by impulsivity in both population and family-based analyses. Knockout of Htr2b increased impulsive behaviours in mice, indicative of predictive validity. Our study shows the potential for identifying and tracing effects of rare alleles in complex behavioural phenotypes using founder populations, and indicates a role for HTR2B in impulsivity. C1 [Bevilacqua, Laura; Yuan, Qiaoping; Zhou, Zhifeng; Hodgkinson, Colin A.; Goldman, David] NIAAA, Neurogenet Lab, NIH, Rockville, MD 20852 USA. [Doly, Stephane; Maroteaux, Luc; Diaz, Silvina; Belmer, Arnaud] INSERM, UMR S 839, F-75654 Paris, France. [Doly, Stephane; Maroteaux, Luc; Diaz, Silvina; Belmer, Arnaud] Univ Paris 06, Inst du Fer Moulin, F-75654 Paris, France. [Kaprio, Jaakko] Univ Helsinki, Dept Publ Hlth, FI-00014 Helsinki, Finland. [Kaprio, Jaakko] Inst Mol Med, FI-00014 Helsinki, Finland. [Kaprio, Jaakko] Natl Inst Hlth & Welf, Unit Child & Adolescent Psychiat, FI-00271 Helsinki, Finland. [Tikkanen, Roope; Virkkunen, Matti] Univ Helsinki, Inst Clin Med, Dept Psychiat, FI-00014 Helsinki, Finland. [Paunio, Tiina; Suvisaari, Jaana] Univ Helsinki, Dept Psychiat, Cent Hosp, FI-00014 Helsinki, Finland. [Wedenoja, Juho] Univ Helsinki, Dept Med Genet, FI-00014 Helsinki, Finland. [Wedenoja, Juho] Univ Helsinki, Inst Mol Med Finland, FI-00014 Helsinki, Finland. [Wedenoja, Juho] Natl Inst Hlth & Welf, FI-00014 Helsinki, Finland. [Dell'Osso, Liliana] Univ Pisa, Dept Psychiat, I-56100 Pisa, Italy. [Coccaro, Emil] Univ Chicago, Pritzker Sch Med, Dept Psychiat, Chicago, IL 60637 USA. [Rose, Richard J.] Indiana Univ, Dept Psychol & Brain Sci, Bloomington, IN 47405 USA. [Virkkunen, Matti] Kellokoski Psychiat Hosp, FI-04500 Kellokoski, Finland. RP Goldman, D (reprint author), NIAAA, Neurogenet Lab, NIH, Rockville, MD 20852 USA. EM davidgoldman@mail.nih.gov RI Goldman, David/F-9772-2010; OI Goldman, David/0000-0002-1724-5405; Maroteaux, Luc/0000-0002-9499-8603; Wedenoja, Juho/0000-0002-6155-0378; Kaprio, Jaakko/0000-0002-3716-2455 FU National Institute on Alcohol Abuse and Alcoholism, NIH; Academy of Finland Centre of Excellence in Complex Disease Genetics; National Institute on Alcohol Abuse and Alcoholism [AA-12502, AA-09203]; Academy of Finland [100499, 205585, 118555]; Centre National de la Recherche Scientifique; Institut National de la Sante et de la Recherche Medicale; Universite Pierre et Marie Curie; Fondation de France; Fondation pour la Recherche Medicale; French Ministry of Research (Agence Nationale pour la Recherche); European Union; IBRO; Region Ile de France DIM STEM FX This study is dedicated to the memory of L.P. and M. Linnoila. We thank L. Akhtar for assistance with tissue culture, C. Marietta for assistance with measurement of receptor protein levels, V. Srivastava and G. Yamini for discussions, and P.-H. Shen for contributions to ancestry analyses. M. Eggert and L. Brown assisted with clinical ascertainment and assessment of the University of Helsinki sample. We thank M. Linnoila for his contributions to the collection of the University of Helsinki sample. E. Kempas assisted with genotyping. J.-M. Launay measured plasma testosterone levels in Htr2b-/- mice. We also thank A. Tuulio-Henriksson, E. Vuoksimaa, A. Happola and L. Arala. This work was supported by the Intramural Research Program of the National Institute on Alcohol Abuse and Alcoholism, NIH and the Academy of Finland Centre of Excellence in Complex Disease Genetics. The FinnTwin12 and FinnTwin16 studies were supported by the National Institute on Alcohol Abuse and Alcoholism (AA-12502 and AA-09203 to R.J.R.), and by the Academy of Finland (100499, 205585 and 118555 to J.K.). The studies on Htr2b-/- mice were supported by the Centre National de la Recherche Scientifique, the Institut National de la Sante et de la Recherche Medicale, the Universite Pierre et Marie Curie, and by grants from the Fondation de France, the Fondation pour la Recherche Medicale, the French Ministry of Research (Agence Nationale pour la Recherche), and the European Union. L.M.'s team is an "Equipe Fondation pour la Recherche Medicale''. S. Diaz is supported by a fellowship from IBRO and Region Ile de France DIM STEM. NR 39 TC 100 Z9 111 U1 2 U2 19 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0028-0836 J9 NATURE JI Nature PD DEC 23 PY 2010 VL 468 IS 7327 BP 1061 EP U460 DI 10.1038/nature09629 PG 8 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 697XT UT WOS:000285553800050 PM 21179162 ER PT J AU Jatoi, I Anderson, WF AF Jatoi, Ismail Anderson, William F. TI Lessons from the Mammography Wars SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Letter ID CANCER C1 [Jatoi, Ismail] Univ Texas Hlth Sci Ctr San Antonio, San Antonio, TX 78229 USA. [Anderson, William F.] NCI, Rockville, MD USA. RP Jatoi, I (reprint author), Univ Texas Hlth Sci Ctr San Antonio, San Antonio, TX 78229 USA. EM jatoi@uthscsa.edu NR 7 TC 1 Z9 1 U1 0 U2 1 PU MASSACHUSETTS MEDICAL SOC PI WALTHAM PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD DEC 23 PY 2010 VL 363 IS 26 BP 2569 EP 2570 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA 697YL UT WOS:000285555600029 PM 21175333 ER PT J AU Cai, ML Huang, Y Craigie, R Clore, GM AF Cai, Mengli Huang, Ying Craigie, Robert Clore, G. Marius TI Structural Basis of the Association of HIV-1 Matrix Protein with DNA SO PLOS ONE LA English DT Article ID PARAMAGNETIC RELAXATION ENHANCEMENT; VIRUS TYPE-1 MATRIX; NUCLEAR-LOCALIZATION SIGNAL; DIPOLAR COUPLINGS; CRYSTAL-STRUCTURES; NONDIVIDING CELLS; MACROMOLECULES; INFECTION; BINDING; DOMAIN AB HIV-1 matrix (MA) is a multifunctional protein that is synthesized as a polyprotein that is cleaved by protease during viral maturation. MA contains a cluster of basic residues whose role is controversial. Proposed functions include membrane anchoring, facilitating viral assembly, and directing nuclear import of the viral DNA. Since MA has been reported to be a component of the preintegration complex (PIC), we have used NMR to probe its interaction with other PIC components. We show that MA interacts with DNA and this is likely sufficient to account for its association with the PIC. C1 [Cai, Mengli; Clore, G. Marius] NIDDKD, Chem Phys Lab, NIH, Bethesda, MD 20892 USA. [Huang, Ying; Craigie, Robert] NIDDKD, Mol Biol Lab, NIH, Bethesda, MD 20892 USA. RP Cai, ML (reprint author), NIDDKD, Chem Phys Lab, NIH, Bldg 2, Bethesda, MD 20892 USA. EM robertc@mail.nih.gov; mariusc@mail.nih.gov RI Clore, G. Marius/A-3511-2008 OI Clore, G. Marius/0000-0003-3809-1027 FU NIDDK; NIH; Office of the Director of the NIH FX This work was supported by the Intramural Program of NIDDK, NIH and by the AIDS Targeted Antiviral Program of the Office of the Director of the NIH (to G.M.C. and R.C.). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 28 TC 13 Z9 14 U1 0 U2 5 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 185 BERRY ST, STE 1300, SAN FRANCISCO, CA 94107 USA SN 1932-6203 J9 PLOS ONE JI PLoS One PD DEC 23 PY 2010 VL 5 IS 12 AR e15675 DI 10.1371/journal.pone.0015675 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 698FO UT WOS:000285579200028 PM 21203471 ER PT J AU Mukhopadhyay, P Mukherjee, S Ahsan, K Bagchi, A Pacher, P Das, DK AF Mukhopadhyay, Partha Mukherjee, Subhendu Ahsan, Kaimul Bagchi, Angshuman Pacher, Pal Das, Dipak K. TI Restoration of Altered MicroRNA Expression in the Ischemic Heart with Resveratrol SO PLOS ONE LA English DT Article ID BREAST-CANCER CELLS; NITRIC-OXIDE; SURVIVAL SIGNAL; MECHANISM; STRESS; CARDIOPROTECTION; PROGNOSIS; DIAGNOSIS; PATHWAY; SIRT1 AB Background: Resveratrol, a constituent of red wine, is important for cardioprotection. MicroRNAs are known regulators for genes involved in resveratrol-mediated cardiac remodeling and the regulatory pathway involving microRNA has not been studied so far. Methods: We explored the cardioprotection by resveratrol in ischemia/reperfusion model of rat and determined cardiac functions. miRNA profile was determined from isolated RNA using quantitative Real-time PCR based array. Systemic analyses of miRNA array and theirs targets were determined using a number of computational approaches. Results: Cardioprotection by resveratrol and its derivative in ischemia/reperfusion [I/R] rat model was examined with miRNA expression profile. Unique expression pattern were found for each sample, particularly with resveratrol [pure compound] and longevinex [commercial resveratrol formulation] pretreated hearts. Longevinex and resveratrol pretreatment modulates the expression pattern of miRNAs close to the control level based on PCA analyses. Differential expression was observed in over 25 miRNAs, some of them, such as miR-21 were previously implicated in cardiac remodeling. The target genes for the differentially expressed miRNA include genes of various molecular function such as metal ion binding, sodium-potassium ion, transcription factors, which may play key role in reducing I/R injury. Conclusion: Rats pretreated with resveratrol for 3 weeks leads to significant cardioprotection against ischemia/reperfusion injury. A unique signature of miRNA profile is observed in control heart pretreated with resveratrol or longevinex. We have determined specific group of miRNA in heart that have altered during IR injuries. Most of those altered microRNA expressions modulated close to their basal level in resveratrol or longevinex treated I/R mice. C1 [Mukhopadhyay, Partha; Pacher, Pal] NIAAA, Lab Physiol Studies, NIH, Bethesda, MD USA. [Bagchi, Angshuman] Buck Inst Age Res, Novato, CA USA. [Mukherjee, Subhendu; Ahsan, Kaimul; Das, Dipak K.] Univ Connecticut, Sch Med, Cardiovasc Res Ctr, Farmington, CT USA. RP Mukhopadhyay, P (reprint author), NIAAA, Lab Physiol Studies, NIH, Bethesda, MD USA. EM ddas@neuron.uchc.edu RI MUKHOPADHYAY, PARTHA/G-3890-2010; Pacher, Pal/B-6378-2008; OI MUKHOPADHYAY, PARTHA/0000-0002-1178-1274; Pacher, Pal/0000-0001-7036-8108; Mukherjee, Subhendu/0000-0002-4851-4428 FU NIH [HL 34360, HL 22559, HL 33889]; NIAAA/NIH FX This study was supported in part by NIH HL 34360, HL 22559 and HL 33889 (to D. K. Das) and Intramural Research Program of the NIAAA/NIH (to P. Pacher). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 38 TC 43 Z9 46 U1 0 U2 7 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 185 BERRY ST, STE 1300, SAN FRANCISCO, CA 94107 USA SN 1932-6203 J9 PLOS ONE JI PLoS One PD DEC 23 PY 2010 VL 5 IS 12 AR e15705 DI 10.1371/journal.pone.0015705 PG 8 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 698FO UT WOS:000285579200031 PM 21203465 ER PT J AU Johnson, WE Onorato, DP Roelke, ME Land, ED O'Brien, SJ AF Johnson, Warren E. Onorato, David P. Roelke, Melody E. Land, E. Darrell O'Brien, Stephen J. TI Genetic Future for Florida Panthers Response SO SCIENCE LA English DT Letter C1 [Johnson, Warren E.; Roelke, Melody E.; O'Brien, Stephen J.] NCI, SAIC Frederick, Lab Genom Divers, Frederick, MD 21702 USA. [Onorato, David P.; Land, E. Darrell] Florida Fish & Wildlife Conservat Commiss, Naples, FL 34114 USA. RP Johnson, WE (reprint author), NCI, SAIC Frederick, Lab Genom Divers, Frederick, MD 21702 USA. EM warjohns@mail.nih.gov RI Johnson, Warren/D-4149-2016 OI Johnson, Warren/0000-0002-5954-186X NR 0 TC 1 Z9 1 U1 3 U2 34 PU AMER ASSOC ADVANCEMENT SCIENCE PI WASHINGTON PA 1200 NEW YORK AVE, NW, WASHINGTON, DC 20005 USA SN 0036-8075 J9 SCIENCE JI Science PD DEC 23 PY 2010 VL 330 IS 6012 BP 1744 EP 1744 DI 10.1126/science.330.6012.1744-b PG 1 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 698OS UT WOS:000285603700011 ER PT J AU Gerstein, MB Lu, ZJ Van Nostrand, EL Cheng, C Arshinoff, BI Liu, T Yip, KY Robilotto, R Rechtsteiner, A Ikegami, K Alves, P Chateigner, A Perry, M Morris, M Auerbach, RK Feng, X Leng, J Vielle, A Niu, W Rhrissorrakrai, K Agarwal, A Alexander, RP Barber, G Brdlik, CM Brennan, J Brouillet, JJ Carr, A Cheung, MS Clawson, H Contrino, S Dannenberg, LO Dernburg, AF Desai, A Dick, L Dose, AC Du, JA Egelhofer, T Ercan, S Euskirchen, G Ewing, B Feingold, EA Gassmann, R Good, PJ Green, P Gullier, F Gutwein, M Guyer, MS Habegger, L Han, T Henikoff, JG Henz, SR Hinrichs, A Holster, H Hyman, T Iniguez, AL Janette, J Jensen, M Kato, M Kent, WJ Kephart, E Khivansara, V Khurana, E Kim, JK Kolasinska-Zwierz, P Lai, EC Latorre, I Leahey, A Lewis, S Lloyd, P Lochovsky, L Lowdon, RF Lubling, Y Lyne, R MacCoss, M Mackowiak, SD Mangone, M Mckay, S Mecenas, D Merrihew, G Miller, DM Muroyama, A Murray, JI Ooi, SL Pham, H Phippen, T Preston, EA Rajewsky, N Ratsch, G Rosenbaum, H Rozowsky, J Rutherford, K Ruzanov, P Sarov, M Sasidharan, R Sboner, A Scheid, P Segal, E Shin, HJ Shou, C Slack, FJ Slightam, C Smith, R Spencer, WC Stinson, EO Taing, S Takasaki, T Vafeados, D Voronina, K Wang, GL Washington, NL Whittle, CM Wu, BJ Yan, KK Zeller, G Zha, Z Zhong, M Zhou, XL Ahringer, J Strome, S Gunsalus, KC Micklem, G Liu, XS Reinke, V Kim, SK Hillier, LW Henikoff, S Piano, F Snyder, M Stein, L Lieb, JD Waterston, RH AF Gerstein, Mark B. Lu, Zhi John Van Nostrand, Eric L. Cheng, Chao Arshinoff, Bradley I. Liu, Tao Yip, Kevin Y. Robilotto, Rebecca Rechtsteiner, Andreas Ikegami, Kohta Alves, Pedro Chateigner, Aurelien Perry, Marc Morris, Mitzi Auerbach, Raymond K. Feng, Xin Leng, Jing Vielle, Anne Niu, Wei Rhrissorrakrai, Kahn Agarwal, Ashish Alexander, Roger P. Barber, Galt Brdlik, Cathleen M. Brennan, Jennifer Brouillet, Jeremy Jean Carr, Adrian Cheung, Ming-Sin Clawson, Hiram Contrino, Sergio Dannenberg, Luke O. Dernburg, Abby F. Desai, Arshad Dick, Lindsay Dose, Andrea C. Du, Jiang Egelhofer, Thea Ercan, Sevinc Euskirchen, Ghia Ewing, Brent Feingold, Elise A. Gassmann, Reto Good, Peter J. Green, Phil Gullier, Francois Gutwein, Michelle Guyer, Mark S. Habegger, Lukas Han, Ting Henikoff, Jorja G. Henz, Stefan R. Hinrichs, Angie Holster, Heather Hyman, Tony Iniguez, A. Leo Janette, Judith Jensen, Morten Kato, Masaomi Kent, W. James Kephart, Ellen Khivansara, Vishal Khurana, Ekta Kim, John K. Kolasinska-Zwierz, Paulina Lai, Eric C. Latorre, Isabel Leahey, Amber Lewis, Suzanna Lloyd, Paul Lochovsky, Lucas Lowdon, Rebecca F. Lubling, Yaniv Lyne, Rachel MacCoss, Michael Mackowiak, Sebastian D. Mangone, Marco Mckay, Sheldon Mecenas, Desirea Merrihew, Gennifer Miller, David M., III Muroyama, Andrew Murray, John I. Ooi, Siew-Loon Pham, Hoang Phippen, Taryn Preston, Elicia A. Rajewsky, Nikolaus Raetsch, Gunnar Rosenbaum, Heidi Rozowsky, Joel Rutherford, Kim Ruzanov, Peter Sarov, Mihail Sasidharan, Rajkumar Sboner, Andrea Scheid, Paul Segal, Eran Shin, Hyunjin Shou, Chong Slack, Frank J. Slightam, Cindie Smith, Richard Spencer, William C. Stinson, E. O. Taing, Scott Takasaki, Teruaki Vafeados, Dionne Voronina, Ksenia Wang, Guilin Washington, Nicole L. Whittle, Christina M. Wu, Beijing Yan, Koon-Kiu Zeller, Georg Zha, Zheng Zhong, Mei Zhou, Xingliang Ahringer, Julie Strome, Susan Gunsalus, Kristin C. Micklem, Gos Liu, X. Shirley Reinke, Valerie Kim, Stuart K. Hillier, LaDeana W. Henikoff, Steven Piano, Fabio Snyder, Michael Stein, Lincoln Lieb, Jason D. Waterston, Robert H. CA modENCODE Consortium TI Integrative Analysis of the Caenorhabditis elegans Genome by the modENCODE Project SO SCIENCE LA English DT Article ID C. ELEGANS; NUCLEOSOME ORGANIZATION; TRANSCRIPTION FACTORS; RNA-SEQ; REVEALS; EXPRESSION; EMBRYOS; NETWORK; DNA; CHROMATIN AB We systematically generated large-scale data sets to improve genome annotation for the nematode Caenorhabditis elegans, a key model organism. These data sets include transcriptome profiling across a developmental time course, genome-wide identification of transcription factor-binding sites, and maps of chromatin organization. From this, we created more complete and accurate gene models, including alternative splice forms and candidate noncoding RNAs. We constructed hierarchical networks of transcription factor-binding and microRNA interactions and discovered chromosomal locations bound by an unusually large number of transcription factors. Different patterns of chromatin composition and histone modification were revealed between chromosome arms and centers, with similarly prominent differences between autosomes and the X chromosome. Integrating data types, we built statistical models relating chromatin, transcription factor binding, and gene expression. Overall, our analyses ascribed putative functions to most of the conserved genome. C1 [Gerstein, Mark B.; Lu, Zhi John; Cheng, Chao; Yip, Kevin Y.; Robilotto, Rebecca; Alves, Pedro; Auerbach, Raymond K.; Leng, Jing; Alexander, Roger P.; Habegger, Lukas; Lochovsky, Lucas; Rozowsky, Joel; Sboner, Andrea; Shou, Chong; Yan, Koon-Kiu] Yale Univ, Program Computat Biol & Bioinformat, New Haven, CT 06520 USA. [Gerstein, Mark B.; Lu, Zhi John; Cheng, Chao; Yip, Kevin Y.; Agarwal, Ashish; Alexander, Roger P.; Rozowsky, Joel; Sasidharan, Rajkumar; Sboner, Andrea; Yan, Koon-Kiu] Yale Univ, Dept Mol Biophys & Biochem, New Haven, CT 06520 USA. [Gerstein, Mark B.; Agarwal, Ashish; Du, Jiang] Yale Univ, Dept Comp Sci, New Haven, CT 06511 USA. [Van Nostrand, Eric L.; Brdlik, Cathleen M.; Brouillet, Jeremy Jean; Kim, Stuart K.; Snyder, Michael] Stanford Univ, Med Ctr, Dept Genet, Stanford, CA 94305 USA. [Arshinoff, Bradley I.; Perry, Marc; Feng, Xin; Kephart, Ellen; Lloyd, Paul; Ruzanov, Peter; Zha, Zheng; Stein, Lincoln] Ontario Inst Canc Res, Toronto, ON M5G 0A3, Canada. [Arshinoff, Bradley I.; Stein, Lincoln] Univ Toronto, Dept Mol Genet, Toronto, ON M5S 1A1, Canada. [Liu, Tao; Shin, Hyunjin; Taing, Scott; Liu, X. Shirley] Dana Farber Canc Inst, Dept Biostat & Computat Biol, Boston, MA 02115 USA. [Liu, Tao; Shin, Hyunjin; Liu, X. Shirley] Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA. [Ikegami, Kohta; Brennan, Jennifer; Ercan, Sevinc; Jensen, Morten; Whittle, Christina M.; Zhou, Xingliang; Lieb, Jason D.] Univ N Carolina, Dept Biol, Chapel Hill, NC 27599 USA. [Ikegami, Kohta; Brennan, Jennifer; Ercan, Sevinc; Jensen, Morten; Whittle, Christina M.; Zhou, Xingliang; Lieb, Jason D.] Univ N Carolina, Carolina Ctr Genome Sci, Chapel Hill, NC 27599 USA. [Chateigner, Aurelien; Carr, Adrian; Contrino, Sergio; Gullier, Francois; Lyne, Rachel; Rutherford, Kim; Smith, Richard; Micklem, Gos] Univ Cambridge, Dept Genet, Cambridge CB2 3EH, England. [Chateigner, Aurelien; Carr, Adrian; Contrino, Sergio; Gullier, Francois; Lyne, Rachel; Rutherford, Kim; Smith, Richard; Micklem, Gos] Cambridge Syst Biol Ctr, Cambridge CB2 1QR, England. [Morris, Mitzi; Rhrissorrakrai, Kahn; Gutwein, Michelle; Khurana, Ekta; Mangone, Marco; Mecenas, Desirea; Scheid, Paul; Gunsalus, Kristin C.; Piano, Fabio] NYU, Dept Biol, Ctr Genom & Syst Biol, New York, NY 10003 USA. [Vielle, Anne; Cheung, Ming-Sin; Kolasinska-Zwierz, Paulina; Latorre, Isabel; Ahringer, Julie] Univ Cambridge, Wellcome Trust Canc Res UK Gurdon Inst, Cambridge CB2 1QN, England. [Niu, Wei; Euskirchen, Ghia; Zhong, Mei; Snyder, Michael] Yale Univ, Dept Mol Cellular & Dev Biol, New Haven, CT 06824 USA. [Niu, Wei; Janette, Judith; Wang, Guilin; Reinke, Valerie] Yale Univ, Sch Med, Dept Genet, New Haven, CT 06520 USA. Univ Calif Santa Cruz, Dept Biomol Engn, Santa Cruz, CA 95064 USA. [Dannenberg, Luke O.; Holster, Heather; Iniguez, A. Leo; Rosenbaum, Heidi] Roche NimbleGen, Madison, WI 53719 USA. [Dernburg, Abby F.; Dose, Andrea C.; Pham, Hoang] Univ Calif Berkeley, Howard Hughes Med Inst, Dept Mol & Cell Biol, Berkeley, CA 94720 USA. [Dernburg, Abby F.; Dose, Andrea C.; Pham, Hoang] Lawrence Berkeley Natl Lab, Div Life Sci, Berkeley, CA 94720 USA. [Desai, Arshad; Gassmann, Reto; Muroyama, Andrew; Voronina, Ksenia] Univ Calif San Diego, Ludwig Inst Canc Res, Dept Cellular & Mol Med, San Diego, CA 92093 USA. [Ewing, Brent; Green, Phil; Leahey, Amber; MacCoss, Michael; Merrihew, Gennifer; Murray, John I.; Preston, Elicia A.; Vafeados, Dionne; Hillier, LaDeana W.; Waterston, Robert H.] Univ Washington, Sch Med, Dept Genome Sci, Seattle, WA 98195 USA. [Feingold, Elise A.; Good, Peter J.; Guyer, Mark S.; Lowdon, Rebecca F.] NHGRI, Div Extramural Res, NIH, Bethesda, MD 20892 USA. [Feng, Xin] SUNY Stony Brook, Dept Biomed Engn, Stony Brook, NY 11794 USA. [Han, Ting; Khivansara, Vishal; Kim, John K.] Univ Michigan, Inst Life Sci, Dept Human Genet, Ann Arbor, MI 48109 USA. [Henikoff, Jorja G.; Ooi, Siew-Loon; Henikoff, Steven] Fred Hutchinson Canc Res Ctr, Div Basic Sci, Seattle, WA 98109 USA. [Raetsch, Gunnar; Zeller, Georg] Max Planck Gesell, Friedrich Miescher Lab, D-72076 Tubingen, Germany. [Hyman, Tony; Sarov, Mihail] Max Planck Inst Mol Cell Biol & Genet, D-01307 Dresden, Germany. [Miller, David M., III; Spencer, William C.] Vanderbilt Univ, Dept Cell & Dev Biol, Nashville, TN 37232 USA. [Kato, Masaomi; Slack, Frank J.] Yale Univ, Dept Mol Cellular & Dev Biol, New Haven, CT 06520 USA. [Henz, Stefan R.] Max Planck Inst Dev Biol, D-72076 Tubingen, Germany. [Lai, Eric C.] Sloan Kettering Inst, New York, NY 10065 USA. [Lewis, Suzanna; Stinson, E. O.; Washington, Nicole L.] Lawrence Berkeley Natl Lab, Genom Div, Berkeley, CA 94720 USA. [Lubling, Yaniv; Segal, Eran] Weizmann Inst Sci, Dept Comp Sci & Appl Math, IL-76100 Rehovot, Israel. [Mackowiak, Sebastian D.; Rajewsky, Nikolaus] Max Delbruck Ctr Mol Med, Div Syst Biol, D-13125 Berlin, Germany. [Mckay, Sheldon; Stein, Lincoln] Cold Spring Harbor Lab, Cold Spring Harbor, NY 11542 USA. [Slightam, Cindie; Wu, Beijing; Kim, Stuart K.] Stanford Univ, Med Ctr, Dept Dev Biol, Stanford, CA 94305 USA. [Zeller, Georg] European Mol Biol Lab, D-69117 Heidelberg, Germany. [Gunsalus, Kristin C.; Piano, Fabio] NYU, Abu Dhabi, U Arab Emirates. [Dick, Lindsay] Rockefeller Univ, David Rockefeller Grad Program, New York, NY 10065 USA. RP Gerstein, MB (reprint author), Yale Univ, Program Computat Biol & Bioinformat, Bass 432,266 Whitney Ave, New Haven, CT 06520 USA. EM modencode.worm.pi@gersteinlab.org RI Spencer, William/E-8529-2010; yu, yan/C-2322-2012; Khurana, Ekta/C-4933-2013; Yan, Koon-Kiu/A-5940-2009; NUI, WEI/B-8300-2011; Gassmann, Reto/M-6488-2013; Zeller, Georg/M-6484-2013; Hyman, Anthony/B-3917-2017; Alexander, Roger/A-8643-2008; Liu, Tao/G-3585-2010; Sboner, Andrea/C-6487-2008; OI Rutherford, Kim/0000-0001-6277-726X; Micklem, Gos/0000-0002-6883-6168; Lewis, Suzanna/0000-0002-8343-612X; Liu, Tao/0000-0003-0446-9001; Lloyd, Paul/0000-0003-3508-5553; Segal, Eran/0000-0002-6859-1164; Hinrichs, Angie/0000-0002-1697-1130; Slack, Frank/0000-0001-8263-0409; Rozowsky, Joel/0000-0002-3565-0762; Dernburg, Abby/0000-0001-8037-1079; Mangone, Marco/0000-0001-7551-8793; Latorre, Isabel/0000-0003-0638-1783; Gassmann, Reto/0000-0002-0360-2977; Zeller, Georg/0000-0003-1429-7485; Hyman, Anthony/0000-0003-3664-154X; Alexander, Roger/0000-0002-2967-7395; Liu, Tao/0000-0002-8818-8313; Sboner, Andrea/0000-0001-6915-3070; McKay, Sheldon/0000-0002-4011-3160 FU NHGRI of the NIH [R01GM088565]; Muscular Dystrophy Association; Pew Charitable Trusts; Helmholtz-Alliance on Systems Biology (Max Delbruck Centrum Systems Biology Network); Wellcome Trust; William H. Gates III Endowed Chair of Biomedical Sciences FX Funding for this work came from the NHGRI of the NIH as part of the modENCODE project, NIH (grant R01GM088565), Muscular Dystrophy Association, and the Pew Charitable Trusts (J.K.K.); the Helmholtz-Alliance on Systems Biology (Max Delbruck Centrum Systems Biology Network) (S.D.M.); the Wellcome Trust (J.A.); the William H. Gates III Endowed Chair of Biomedical Sciences (R.H.W.); and the A. L. Williams Professorship (M.B.G.). M. Snyder has an advisory role with DNANexus, a DNA sequence storage and analysis company. Transfer of GFP-tagged fosmids requires a Materials Transfer Agreement with the Max Planck Institute of Molecular Cell Biology and Genetics. Raw microarray data are available from the Gene Expression Omnibus archive, and raw sequencing data are available from the SRA archive (accessions are in table S18). We appreciate help from S. Anthony, K. Bell, C. Davis, C. Dieterich, Y. Field, A. S. Hammonds, J. Jo, N. Kaplan, A. Manrai, B. Mathey-Prevot, R. McWhirter, S. Mohr, S. Von Stetina, J. Watson, K. Watkins, C. Xue, and Y. Zhang, and B. Carpenter. We thank C. Jan and D. Bartel for sharing data on poly(A) sites before publication, WormBase curator G. Williams for assistance in quality checking and preparing the transcriptomics data sets for publication, as well as his fellow curator P. Davis for reviewing and hand-checking the list of pseudogenes. NR 76 TC 458 Z9 462 U1 6 U2 90 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 DEC 23 PY 2010 VL 330 IS 6012 BP 1775 EP 1787 DI 10.1126/science.1196914 PG 13 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 698OS UT WOS:000285603700031 PM 21177976 ER PT J AU Roy, S Ernst, J Kharchenko, PV Kheradpour, P Negre, N Eaton, ML Landolin, JM Bristow, CA Ma, LJ Lin, MF Washietl, S Arshinoff, BI Ay, F Meyer, PE Robine, N Washington, NL Di Stefano, L Berezikov, E Brown, CD Candeias, R Carlson, JW Carr, A Jungreis, I Marbach, D Sealfon, R Tolstorukov, MY Will, S Alekseyenko, AA Artieri, C Booth, BW Brooks, AN Dai, Q Davis, CA Duff, MO Feng, X Gorchakov, AA Gu, TT Henikoff, JG Kapranov, P Li, RH MacAlpine, HK Malone, J Minoda, A Nordman, J Okamura, K Perry, M Powell, SK Riddle, NC Sakai, A Samsonova, A Sandler, JE Schwartz, YB Sher, N Spokony, R Sturgill, D van Baren, M Wan, KH Yang, L Yu, C Feingold, E Good, P Guyer, M Lowdon, R Ahmad, K Andrews, J Berger, B Brenner, SE Brent, MR Cherbas, L Elgin, SCR Gingeras, TR Grossman, R Hoskins, RA Kaufman, TC Kent, W Kuroda, MI Orr-Weaver, T Perrimon, N Pirrotta, V Posakony, JW Ren, B Russell, S Cherbas, P Graveley, BR Lewis, S Micklem, G Oliver, B Park, PJ Celniker, SE Henikoff, S Karpen, GH Lai, EC MacAlpine, DM Stein, LD White, KP Kellis, M AF Roy, Sushmita Ernst, Jason Kharchenko, Peter V. Kheradpour, Pouya Negre, Nicolas Eaton, Matthew L. Landolin, Jane M. Bristow, Christopher A. Ma, Lijia Lin, Michael F. Washietl, Stefan Arshinoff, Bradley I. Ay, Ferhat Meyer, Patrick E. Robine, Nicolas Washington, Nicole L. Di Stefano, Luisa Berezikov, Eugene Brown, Christopher D. Candeias, Rogerio Carlson, Joseph W. Carr, Adrian Jungreis, Irwin Marbach, Daniel Sealfon, Rachel Tolstorukov, Michael Y. Will, Sebastian Alekseyenko, Artyom A. Artieri, Carlo Booth, Benjamin W. Brooks, Angela N. Dai, Qi Davis, Carrie A. Duff, Michael O. Feng, Xin Gorchakov, Andrey A. Gu, Tingting Henikoff, Jorja G. Kapranov, Philipp Li, Renhua MacAlpine, Heather K. Malone, John Minoda, Aki Nordman, Jared Okamura, Katsutomo Perry, Marc Powell, Sara K. Riddle, Nicole C. Sakai, Akiko Samsonova, Anastasia Sandler, Jeremy E. Schwartz, Yuri B. Sher, Noa Spokony, Rebecca Sturgill, David van Baren, Marijke Wan, Kenneth H. Yang, Li Yu, Charles Feingold, Elise Good, Peter Guyer, Mark Lowdon, Rebecca Ahmad, Kami Andrews, Justen Berger, Bonnie Brenner, Steven E. Brent, Michael R. Cherbas, Lucy Elgin, Sarah C. R. Gingeras, Thomas R. Grossman, Robert Hoskins, Roger A. Kaufman, Thomas C. Kent, William Kuroda, Mitzi I. Orr-Weaver, Terry Perrimon, Norbert Pirrotta, Vincenzo Posakony, James W. Ren, Bing Russell, Steven Cherbas, Peter Graveley, Brenton R. Lewis, Suzanna Micklem, Gos Oliver, Brian Park, Peter J. Celniker, Susan E. Henikoff, Steven Karpen, Gary H. Lai, Eric C. MacAlpine, David M. Stein, Lincoln D. White, Kevin P. Kellis, Manolis CA modENCODE Consortium TI Identification of Functional Elements and Regulatory Circuits by Drosophila modENCODE SO SCIENCE LA English DT Article ID PREDICTIVE CHROMATIN SIGNATURES; TRANSCRIPTION FACTORS; SOMATIC-CELLS; HUMAN GENOME; DNA-BINDING; RNA PATHWAY; MELANOGASTER; SEQUENCE; REGIONS; NETWORK AB To gain insight into how genomic information is translated into cellular and developmental programs, the Drosophila model organism Encyclopedia of DNA Elements (modENCODE) project is comprehensively mapping transcripts, histone modifications, chromosomal proteins, transcription factors, replication proteins and intermediates, and nucleosome properties across a developmental time course and in multiple cell lines. We have generated more than 700 data sets and discovered protein-coding, noncoding, RNA regulatory, replication, and chromatin elements, more than tripling the annotated portion of the Drosophila genome. Correlated activity patterns of these elements reveal a functional regulatory network, which predicts putative new functions for genes, reveals stage-and tissue-specific regulators, and enables gene-expression prediction. Our results provide a foundation for directed experimental and computational studies in Drosophila and related species and also a model for systematic data integration toward comprehensive genomic and functional annotation. C1 [Roy, Sushmita; Ernst, Jason; Kheradpour, Pouya; Bristow, Christopher A.; Lin, Michael F.; Washietl, Stefan; Ay, Ferhat; Meyer, Patrick E.; Di Stefano, Luisa; Candeias, Rogerio; Jungreis, Irwin; Marbach, Daniel; Sealfon, Rachel; Will, Sebastian; Berger, Bonnie; Kellis, Manolis] MIT, Comp Sci & Artificial Intelligence Lab, Cambridge, MA 02139 USA. [Roy, Sushmita; Ernst, Jason; Kheradpour, Pouya; Bristow, Christopher A.; Lin, Michael F.; Jungreis, Irwin; Marbach, Daniel; Sealfon, Rachel; Berger, Bonnie; Kellis, Manolis] MIT, Broad Inst, Cambridge, MA 02140 USA. [Roy, Sushmita; Ernst, Jason; Kheradpour, Pouya; Bristow, Christopher A.; Lin, Michael F.; Jungreis, Irwin; Marbach, Daniel; Sealfon, Rachel; Berger, Bonnie; Kellis, Manolis] Harvard Univ, Cambridge, MA 02140 USA. [Kharchenko, Peter V.; Tolstorukov, Michael Y.; Schwartz, Yuri B.; Park, Peter J.] Harvard Univ, Sch Med, Ctr Biomed Informat, Boston, MA 02115 USA. [Negre, Nicolas; Ma, Lijia; Brown, Christopher D.; Spokony, Rebecca; Grossman, Robert; White, Kevin P.] Univ Chicago, Inst Genom & Syst Biol, Dept Human Genet, Chicago, IL 60637 USA. [Eaton, Matthew L.; MacAlpine, Heather K.; Powell, Sara K.; MacAlpine, David M.] Duke Univ, Med Ctr, Dept Pharmacol & Canc Biol, Durham, NC 27710 USA. [Landolin, Jane M.; Carlson, Joseph W.; Booth, Benjamin W.; Minoda, Aki; Sandler, Jeremy E.; Wan, Kenneth H.; Yu, Charles; Hoskins, Roger A.; Celniker, Susan E.; Karpen, Gary H.] Lawrence Berkeley Natl Lab, Dept Genome Dynam, Berkeley, CA 94720 USA. [Arshinoff, Bradley I.] Univ Toronto, Dept Mol Genet, Toronto, ON M5S 1A1, Canada. [Robine, Nicolas; Dai, Qi; Henikoff, Jorja G.; Okamura, Katsutomo; Lai, Eric C.] Sloan Kettering Inst, New York, NY 10065 USA. [Washington, Nicole L.; Lewis, Suzanna] LBNL, Genome Sci Div, Berkeley, CA 94720 USA. [Carr, Adrian; Russell, Steven; Micklem, Gos] Univ Cambridge, Dept Genet, Cambridge CB2 3EH, England. [Carr, Adrian; Russell, Steven; Micklem, Gos] Univ Cambridge, Cambridge Syst Biol Ctr, Cambridge CB2 3EH, England. [Alekseyenko, Artyom A.; Gorchakov, Andrey A.; Kuroda, Mitzi I.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Med, Boston, MA 02115 USA. [Alekseyenko, Artyom A.; Gorchakov, Andrey A.; Kuroda, Mitzi I.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Genet, Boston, MA 02115 USA. [Artieri, Carlo; Malone, John; Sturgill, David; Oliver, Brian] NIDDK, Sect Dev Genom, Cellular & Dev Biol Lab, NIH, Bethesda, MD 20892 USA. [Davis, Carrie A.; Feng, Xin; Gingeras, Thomas R.] Cold Spring Harbor Lab, Cold Spring Harbor, NY 11724 USA. [Duff, Michael O.; Yang, Li; Graveley, Brenton R.] Univ Connecticut, Stem Cell Inst, Dept Genet & Dev Biol, Farmington, CT 06030 USA. [Gu, Tingting; Riddle, Nicole C.; Elgin, Sarah C. R.] Washington Univ, Dept Biol, St Louis, MO 63130 USA. [Kapranov, Philipp; Gingeras, Thomas R.] Affymetrix, Santa Clara, CA 95051 USA. [Li, Renhua; Feingold, Elise; Good, Peter; Guyer, Mark; Lowdon, Rebecca] NHGRI, Div Extramural Res, NIH, Bethesda, MD 20892 USA. [Arshinoff, Bradley I.; Feng, Xin; Perry, Marc; Stein, Lincoln D.] Ontario Inst Canc Res, Toronto, ON M5G 0A3, Canada. [Samsonova, Anastasia; Perrimon, Norbert] Harvard Univ, Sch Med, Dept Genet, Boston, MA 02115 USA. [Samsonova, Anastasia; Perrimon, Norbert] Harvard Univ, Sch Med, Drosophila RNAi Screening Ctr, Boston, MA 02115 USA. [van Baren, Marijke; Brent, Michael R.] Washington Univ, Ctr Genome Sci, St Louis, MO 63108 USA. [Andrews, Justen; Cherbas, Lucy; Kaufman, Thomas C.; Cherbas, Peter] Indiana Univ, Dept Biol, Bloomington, IN 47405 USA. [Nordman, Jared; Sher, Noa; Orr-Weaver, Terry] Whitehead Inst, Cambridge, MA 02142 USA. [Berezikov, Eugene] Royal Netherlands Acad Arts & Sci, Hubrecht Inst, Utrecht, Netherlands. [Berezikov, Eugene] Univ Med Ctr Utrecht, Utrecht, Netherlands. [Cherbas, Lucy; Cherbas, Peter] Indiana Univ, Ctr Genom & Bioinformat, Bloomington, IN 47405 USA. [Henikoff, Steven] Fred Hutchinson Canc Res Ctr, Div Basic Sci, Seattle, WA 98109 USA. [Posakony, James W.; Ren, Bing] Univ Calif San Diego, Sect Cell & Dev Biol, Div Biol Sci, La Jolla, CA 92093 USA. [Pirrotta, Vincenzo] Rutgers State Univ, Dept Mol Biol & Biochem, Piscataway, NJ 08854 USA. [Brooks, Angela N.; Brenner, Steven E.; Karpen, Gary H.] Univ Calif Berkeley, Dept Mol & Cell Biol, Berkeley, CA 94720 USA. [Sakai, Akiko; Ahmad, Kami] Harvard Univ, Sch Med, Dept Biol Chem & Mol Pharmacol, Boston, MA 02115 USA. [Meyer, Patrick E.] Univ Libre Brussels, Machine Learning Grp, B-1050 Brussels, Belgium. [Di Stefano, Luisa] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Ctr Canc, Charlestown, MA 02129 USA. [Brenner, Steven E.] Univ Calif Berkeley, Dept Plant & Microbial Biol, Berkeley, CA 94720 USA. [Ay, Ferhat] Univ Florida, Gainesville, FL 32611 USA. [Kent, William] Univ Calif Santa Cruz, Sch Engn, Ctr Biomol Sci & Engn, Santa Cruz, CA 95064 USA. [Kent, William] Univ Calif Santa Cruz, Howard Hughes Med Inst, Santa Cruz, CA 95064 USA. [Feng, Xin] SUNY Stony Brook, Dept Biomed Engn, Stony Brook, NY 11794 USA. RP Kellis, M (reprint author), MIT, Comp Sci & Artificial Intelligence Lab, 77 Massachusetts Ave, Cambridge, MA 02139 USA. EM celniker@fruitfly.org; steveh@fhcrc.org; karpen@fruitfly.org; laie@mskcc.org; david.macalpine@duke.edu; lincoln.stein@gmail.com; kpwhite@uchicago.edu; manoli@mit.edu RI Samsonova, Anastasia/Q-7591-2016; Minoda, Aki/D-5335-2017; Sakai, Akiko/A-8929-2010; Berezikov, Eugene/D-3363-2013; Brenner, Steven/A-8729-2008; Venken, Koen/B-9909-2013; Gorchakov, Andrey/N-5840-2015; Eaton, Matthew/C-4408-2011; jiang, lichun/F-3776-2012; White, Rob/G-4835-2012; Russell, Steve/A-4072-2011; Brooks, Angela/B-6173-2011; Graveley, Brenton/C-3108-2013; Hansen, Kasper/E-6094-2011 OI Meyer, Folker/0000-0003-1112-2284; Lloyd, Paul/0000-0003-3508-5553; Bellen, Hugo/0000-0001-5992-5989; Hinrichs, Angie/0000-0002-1697-1130; Negre, Nicolas/0000-0001-9727-3416; Robine, Nicolas/0000-0001-5698-8183; Brown, Christopher/0000-0002-3785-5008; Samsonova, Anastasia/0000-0002-9353-9173; Minoda, Aki/0000-0002-2927-5791; Gingeras, Thomas/0000-0001-9106-3573; Washington, Nicole/0000-0001-8936-9143; Grossman, Robert/0000-0003-3741-5739; Graveley, Brenton/0000-0001-5777-5892; Rutherford, Kim/0000-0001-6277-726X; McKay, Sheldon/0000-0002-4011-3160; Micklem, Gos/0000-0002-6883-6168; Lewis, Suzanna/0000-0002-8343-612X; Berezikov, Eugene/0000-0002-1145-2884; Brenner, Steven/0000-0001-7559-6185; Venken, Koen/0000-0003-0741-4698; Gorchakov, Andrey/0000-0003-2830-4236; jiang, lichun/0000-0003-2462-7636; Russell, Steve/0000-0003-0546-3031; Hansen, Kasper/0000-0003-0086-0687 FU National Human Genome Research Institute [RC2HG005639, U01HG004271, U01HG004258, U01HG004264, U01HG004279, U01HG004261, U01HG004274, U41HG004269]; LBNL [DE-AC02-05CH11231]; NSF [0937060, 0905968, 0644282]; Natural Sciences and Engineering Research Council of Canada (NSERC); Japan Society for the Promotion of Science; Swedish Research Council; NIH National Research Service; National Defense Science and Engineering; Austrian Fonds zur Forderung der wissenschaftlichen Forschung; Leukemia and Lymphoma Society; Lilly-Life Sciences Research Foundation; Affymetrix; Swiss National Science Foundation; German Research Foundation [WI 3628/1-1]; HHMI; Indiana Genomics Initiative; NIDDK genomics core laboratory; NIH [R01HG004037]; Sloan Foundation FX This work was supported by the National Human Genome Research Institute as part of the modENCODE project under RC2HG005639 (M.K.), U01HG004271 (S.E.C.), U01HG004258 (G.H.K.), U01HG004264 (K.P.W.), U01HG004279 (D.M.M.), U01HG004261 (E.L.), U01HG004274 (S.H.), and U41HG004269 (L.S.). Awards to S.E.C. and G.H.K. were carried out at LBNL under contract no. DE-AC02-05CH11231. Additional support was provided by the NSF under grant 0937060 to the Computing Research Association for the CIFellows Project (S.R.) and under award no. 0905968 (J.E.), a Natural Sciences and Engineering Research Council of Canada (NSERC) fellowship (B.A.), T. Kahveci (F.A.), the Japan Society for the Promotion of Science (K.O.), the Swedish Research Council (Q.D.), a NIH National Research Service Award postdoctoral fellowship (C.A.B.), a National Defense Science and Engineering Graduate Fellowship (R.S.), an Erwin Schrodinger Fellowship of the Austrian Fonds zur Forderung der wissenschaftlichen Forschung (S.W.), a Leukemia and Lymphoma Society fellowship (S.W.), a Lilly-Life Sciences Research Foundation fellowship (C.D.B.), a NSERC postdoctoral fellowship (C. G. A.), Affymetrix (T.G.R.), a fellowship from the Swiss National Science Foundation (D.M.), a German Research Foundation grant WI 3628/1-1 (S.W.), a HHMI Damon Runyon Cancer Research fellowship (J.T.N.), the Indiana Genomics Initiative (T.C.K.), H. Smith and the NIDDK genomics core laboratory (B.O.), NIH R01HG004037, NSF CAREER award 0644282, and the Sloan Foundation (M.K.). A full list of author contributions is available in the SOM. NR 69 TC 524 Z9 531 U1 17 U2 82 PU AMER ASSOC ADVANCEMENT SCIENCE PI WASHINGTON PA 1200 NEW YORK AVE, NW, WASHINGTON, DC 20005 USA SN 0036-8075 J9 SCIENCE JI Science PD DEC 23 PY 2010 VL 330 IS 6012 BP 1787 EP 1797 DI 10.1126/science.1198374 PG 11 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 698OS UT WOS:000285603700032 ER PT J AU Johnson, RC Nelson, GW Troyer, JL Lautenberger, JA Kessing, BD Winkler, CA O'Brien, SJ AF Johnson, Randall C. Nelson, George W. Troyer, Jennifer L. Lautenberger, James A. Kessing, Bailey D. Winkler, Cheryl A. O'Brien, Stephen J. TI Accounting for multiple comparisons in a genome-wide association study (GWAS) SO BMC GENOMICS LA English DT Article ID SINGLE-NUCLEOTIDE POLYMORPHISMS; LINKAGE DISEQUILIBRIUM; PRINCIPAL-COMPONENTS; GENETIC ASSOCIATION; HAPLOTYPE BLOCKS; RECOMBINATION; HISTORY; MAP; LD AB Background: As we enter an era when testing millions of SNPs in a single gene association study will become the standard, consideration of multiple comparisons is an essential part of determining statistical significance. Bonferroni adjustments can be made but are conservative due to the preponderance of linkage disequilibrium (LD) between genetic markers, and permutation testing is not always a viable option. Three major classes of corrections have been proposed to correct the dependent nature of genetic data in Bonferroni adjustments: permutation testing and related alternatives, principal components analysis (PCA), and analysis of blocks of LD across the genome. We consider seven implementations of these commonly used methods using data from 1514 European American participants genotyped for 700,078 SNPs in a GWAS for AIDS. Results: A Bonferroni correction using the number of LD blocks found by the three algorithms implemented by Haploview resulted in an insufficiently conservative threshold, corresponding to a genome-wide significance level of alpha = 0.15 0.20. We observed a moderate increase in power when using PRESTO, SLIDE, and simpleM when compared with traditional Bonferroni methods for population data genotyped on the Affymetrix 6.0 platform in European Americans (alpha = 0.05 thresholds between 1 x 10(-7) and 7 x 10(-8)). Conclusions: Correcting for the number of LD blocks resulted in an anti-conservative Bonferroni adjustment. SLIDE and simpleM are particularly useful when using a statistical test not handled in optimized permutation testing packages, and genome-wide corrected p-values using SLIDE, are much easier to interpret for consumers of GWAS studies. C1 [Lautenberger, James A.; O'Brien, Stephen J.] NCI, Lab Genom Divers, Frederick, MD 21701 USA. [Johnson, Randall C.; Nelson, George W.; Troyer, Jennifer L.; Kessing, Bailey D.; Winkler, Cheryl A.] NCI, Basic Res Program, SAIC Frederick Inc, Frederick, MD 21701 USA. [Johnson, Randall C.] Conservatoire Natl Arts & Metiers, Chaire Bioinformat, F-75003 Paris, France. RP O'Brien, SJ (reprint author), NCI, Lab Genom Divers, Frederick, MD 21701 USA. EM obrien@ncifcrf.gov RI Troyer, Jennifer/B-8415-2012; Johnson, Randall/B-1517-2014 OI Johnson, Randall/0000-0001-7754-0847 FU NationalCancer Institute, National Institutes of Health [HHSN261200800001E]; NIH, National Cancer Institute, Center for Cancer Research 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. We thank the individuals who participated in the HGDS, MACS, MHCS, and SFCC cohort studies, as well as the physicians and researchers responsible for recruitment and sample collection. We also thank Michelle Hall, Michael Malasky, Lisa Maslan, Mary McNally, and Jami Troxler who performed the genotyping, Leslie Chinn, Sher Hendrickson, Carl Mclntosh, and Joan Pontius who helped with quality control and annotation of the GWAS data, and Julie Johnson for her comments and discussion. This project has been funded in whole or in part with federal funds from the NationalCancer Institute, National Institutes of Health, under contract HHSN261200800001E. The content of this publication does not necessarily reflect the views or policies of the Department of Health and Human Services, nor does mention of trade names, commercial products, or organizations imply endorsement by the US Government. This research was supported [in part] by the Intramural Research Program of NIH, National Cancer Institute, Center for Cancer Research. NR 32 TC 63 Z9 65 U1 0 U2 20 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 DEC 22 PY 2010 VL 11 AR 724 DI 10.1186/1471-2164-11-724 PG 6 WC Biotechnology & Applied Microbiology; Genetics & Heredity SC Biotechnology & Applied Microbiology; Genetics & Heredity GA 709FU UT WOS:000286424100001 PM 21176216 ER PT J AU Urzua, U Owens, GA Zhang, GM Cherry, JM Sharp, JJ Munroe, DJ AF Urzua, Ulises Owens, Garrison A. Zhang, Gen-Mu Cherry, James M. Sharp, John J. Munroe, David J. TI Tumor and reproductive traits are linked by RNA metabolism genes in the mouse ovary: a transcriptome-phenotype association analysis SO BMC GENOMICS LA English DT Article; Proceedings Paper CT 5th International Conference of the Brazilian-Association-for-Bioinformatics-and-Computational-Biology CY OCT 18-22, 2009 CL Angra dos Reis, BRAZIL SP Brazilian Assoc Bioinformat & Computational Biol ID GRANULOSA-CELLS; FOLLICLE DEVELOPMENT; CDNA MICROARRAY; MURINE MODEL; EXPRESSION; CANCER; OVULATION; PATHWAY; PHOSPHORYLATION; IDENTIFICATION AB Background: The link between reproductive life history and incidence of ovarian tumors is well known. Periods of reduced ovulations may confer protection against ovarian cancer. Using phenotypic data available for mouse, a possible association between the ovarian transcriptome, reproductive records and spontaneous ovarian tumor rates was investigated in four mouse inbred strains. NIA15k-DNA microarrays were employed to obtain expression profiles of BalbC, C57BL6, FVB and SWR adult ovaries. Results: Linear regression analysis with multiple-test control (adjusted p <= 0.05) resulted in ovarian tumor frequency (OTF) and number of litters (NL) as the top-correlated among five tested phenotypes. Moreover, nearly one-hundred genes were coincident between these two traits and were decomposed in 76 OTF(-) NL(+) and 20 OTF(+) NL(-) genes, where the plus/minus signs indicate the direction of correlation. Enriched functional categories were RNA-binding/mRNA-processing and protein folding in the OTF(-) NL(+) and the OTF(+) NL(-) subsets, respectively. In contrast, no associations were detected between OTF and litter size (LS), the latter a measure of ovulation events in a single estrous cycle. Conclusion: Literature text-mining pointed to post-transcriptional control of ovarian processes including oocyte maturation, folliculogenesis and angiogenesis as possible causal relationships of observed tumor and reproductive phenotypes. We speculate that repetitive cycling instead of repetitive ovulations represent the actual link between ovarian tumorigenesis and reproductive records. C1 [Urzua, Ulises] Univ Chile, ICBM, Lab Genom Aplicada, Santiago, Chile. [Owens, Garrison A.; Cherry, James M.; Munroe, David J.] SAIC NCI Frederick, Lab Mol Technol, Frederick, MD 21701 USA. [Zhang, Gen-Mu] SAIC NCI Frederick, Lab Anim Sci Program, Frederick, MD 21702 USA. [Sharp, John J.] Baylor Coll Med, Ctr Comparat Med, Houston, TX 77030 USA. RP Urzua, U (reprint author), Univ Chile, ICBM, Lab Genom Aplicada, Independencia 1027, Santiago, Chile. EM uurzua@med.uchile.cl RI Urzua, Ulises/A-3982-2013; OI Urzua, Ulises/0000-0003-0522-5754 FU PHS HHS [N01-C0-12400] NR 53 TC 2 Z9 2 U1 1 U2 3 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 DEC 22 PY 2010 VL 11 SU 5 AR S1 DI 10.1186/1471-2164-11-S5-S1 PG 11 WC Biotechnology & Applied Microbiology; Genetics & Heredity SC Biotechnology & Applied Microbiology; Genetics & Heredity GA 729AA UT WOS:000287915800001 PM 21210965 ER PT J AU Hanover, JA AF Hanover, John A. TI Epigenetics Gets Sweeter: O-GlcNAc Joins the "Histone Code" SO CHEMISTRY & BIOLOGY LA English DT Editorial Material ID TETRATRICOPEPTIDE REPEATS; N-ACETYLGLUCOSAMINE; TRANSFERASE; GLYCOSYLATION; CHROMATIN; PROTEINS; GENE AB O-GlcNAcylation has now been added to the growing list of histone modifications making up the multifaceted "histone-code" (Sakabe et al., 2010). The sites of O-GlcNAc-histone modification hint at a role in chromatin remodeling, thus adding to mounting evidence that O-GlcNAc cycling sits atop a robust regulatory network maintaining higher-order chromatin structure and epigenetic memory. C1 NIDDK, Cellular & Mol Biol Lab, NIH, Bethesda, MD 20892 USA. RP Hanover, JA (reprint author), NIDDK, Cellular & Mol Biol Lab, NIH, Bethesda, MD 20892 USA. EM jah@helix.nih.gov FU Intramural NIH HHS [ZIA DK060103-04] NR 12 TC 21 Z9 21 U1 0 U2 7 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 1074-5521 J9 CHEM BIOL JI Chem. Biol. PD DEC 22 PY 2010 VL 17 IS 12 BP 1272 EP 1274 DI 10.1016/j.chembiol.2010.12.001 PG 3 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 717BA UT WOS:000287016000004 PM 21168762 ER PT J AU Mathews, JM Watson, SL Snyder, RW Burgess, JP Morgan, DL AF Mathews, James M. Watson, Scott L. Snyder, Rodney W. Burgess, Jason P. Morgan, Daniel L. TI Reaction of the Butter Flavorant Diacetyl (2,3-Butanedione) with N-alpha-Acetylarginine: A Model for Epitope Formation with Pulmonary Proteins in the Etiology of Obliterative Bronchiolitis SO JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY LA English DT Article DE Diacetyl; 2,3-butanedione; artificial butter flavoring; arginine adducts; toxicity ID PERFORMANCE LIQUID-CHROMATOGRAPHY; ARGININE; WORKERS; LUNG AB The butter flavorant diacetyl (2,3-butanedione) is implicated in causing obliterative bronchiolitis in microwave popcorn plant workers. Because diacetyl modifies arginine residues, an immunological basis for its toxicity is under investigation. Reaction products of diacetyl with N-alpha-acetylarginine (AcArg) were determined as a model for hapten formation, with characterization by mass spectrometry, NMR, and HPLC with UV detection and radiodetection. Four products were identified by LC-MS, each with a positive ion of m/z 303 (diacetyl + AcArg); one pair displayed an additional ion at m/z 217 (AcArg), the other pair at m/z 285 (- H(2)O). Their (1)H-(13)C NMR correlation spectra were consistent with the addition of one or two of the guanidine nitrogens to form aminols. Open-chain pairs interconverted at pH 2, as did the cyclized, but all four interconverted at neutral pH. This is the first structural characterization of the covalent adducts between diacetyl and an arginine moiety. C1 [Mathews, James M.; Watson, Scott L.; Snyder, Rodney W.; Burgess, Jason P.] RTI Int, Res Triangle Pk, NC 27709 USA. [Morgan, Daniel L.] NIEHS, Res Triangle Pk, NC 27709 USA. RP Mathews, JM (reprint author), RTI Int, POB 12194, Res Triangle Pk, NC 27709 USA. EM mathews@rti.org FU Intramural NIH HHS [ZIA ES101865-06]; NIEHS NIH HHS [N01ES75563]; PHS HHS [HHSN29120077563] NR 25 TC 18 Z9 18 U1 0 U2 10 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0021-8561 J9 J AGR FOOD CHEM JI J. Agric. Food Chem. PD DEC 22 PY 2010 VL 58 IS 24 BP 12761 EP 12768 DI 10.1021/jf103251w PG 8 WC Agriculture, Multidisciplinary; Chemistry, Applied; Food Science & Technology SC Agriculture; Chemistry; Food Science & Technology GA 693PQ UT WOS:000285236400027 PM 21077678 ER PT J AU Sosa, MS Lopez-Haber, C Yang, CF Wang, HB Lemmon, MA Busillo, JM Luo, JS Benovic, JL Klein-Szanto, A Yagi, H Gutkind, JS Parsons, RE Kazanietz, MG AF Sosa, Maria Soledad Lopez-Haber, Cynthia Yang, Chengfeng Wang, HongBin Lemmon, Mark A. Busillo, John M. Luo, Jiansong Benovic, Jeffrey L. Klein-Szanto, Andres Yagi, Hiroshi Gutkind, J. Silvio Parsons, Ramon E. Kazanietz, Marcelo G. TI Identification of the Rac-GEF P-Rex1 as an Essential Mediator of ErbB Signaling in Breast Cancer SO MOLECULAR CELL LA English DT Article ID COMPARATIVE GENOMIC HYBRIDIZATION; NUCLEOTIDE EXCHANGE FACTOR; GROWTH-FACTOR RECEPTOR; INDUCED CELL MOTILITY; BETA-GAMMA-SUBUNITS; CYCLIN D1; NEUTROPHIL FUNCTION; EPITHELIAL-CELLS; UP-REGULATION; RHO GTPASES AB While the small GTPase Rac1 and its effectors are well-established mediators of mitogenic and motile signaling by tyrosine kinase receptors and have been implicated in breast tumorigenesis, little is known regarding the exchange factors (Rac-GEFs) that mediate ErbB receptor responses. Here, we identify the PIP(3)-G beta gamma-dependent Rac-GEF P-Rex1 as an essential mediator of Rac1 activation, motility, cell growth, and tumorigenesis driven by ErbB receptors in breast cancer cells. Notably, activation of P-Rex1 in breast cancer cells requires the convergence of inputs from ErbB receptors and a G beta gamma- and PI3K gamma-dependent pathway. Moreover, we identified the GPCR CXCR4 as a crucial mediator of P-Rex1/Rac1 activation in response to ErbB ligands. P-Rex1 is highly overexpressed in human breast cancers and their derived cell lines, particularly those with high ErbB2 and ER expression. In addition to the prognostic and therapeutic implications, our findings reveal an ErbB effector pathway that is crucial for breast cancer progression. C1 [Sosa, Maria Soledad; Lopez-Haber, Cynthia; Wang, HongBin; Kazanietz, Marcelo G.] Univ Penn, Sch Med, Dept Pharmacol, Philadelphia, PA 19104 USA. [Lemmon, Mark A.] Univ Penn, Sch Med, Dept Biochem & Biophys, Philadelphia, PA 19104 USA. [Yang, Chengfeng] Michigan State Univ, Ctr Integrat Toxicol, E Lansing, MI 48824 USA. [Busillo, John M.; Luo, Jiansong; Benovic, Jeffrey L.] Thomas Jefferson Univ, Dept Biochem & Mol Biol, Philadelphia, PA 19107 USA. [Klein-Szanto, Andres] Fox Chase Canc Ctr, Philadelphia, PA 19111 USA. [Yagi, Hiroshi; Gutkind, J. Silvio] NIDCR, Oral & Pharyngeal Canc Branch, Bethesda, MD 20892 USA. [Parsons, Ramon E.] Columbia Univ, Med Ctr, Inst Canc Genet, New York, NY 10032 USA. RP Kazanietz, MG (reprint author), Univ Penn, Sch Med, Dept Pharmacol, Philadelphia, PA 19104 USA. EM marcelog@upenn.edu RI wang, hongbin/E-5541-2011; Gutkind, J. Silvio/A-1053-2009; OI Lemmon, Mark/0000-0002-3379-5319 FU NIH [R01CA74197, R01CA129133, R01CA139120]; Susan Komen Foundation [KG090522]; NIDCR, NIH; [R01CA129626]; [R01CA155117] FX This work is supported by grants R01CA74197, R01CA129133, and R01CA139120 (NIH) and KG090522 (Susan Komen Foundation for the Cure) to M.G.K. and by grant R01CA129626 to J.L.B. H.Y. and J.S.G. are supported by the Intramural Program, NIDCR, NIH. R.E.P. is supported by grant R01CA155117. We thank Andy Cucchiara (UPenn) for help with statistical analyses and Celine Lefebvre (Columbia University) for support with microarray data analysis. NR 54 TC 75 Z9 75 U1 0 U2 12 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 1097-2765 J9 MOL CELL JI Mol. Cell PD DEC 22 PY 2010 VL 40 IS 6 BP 877 EP 892 DI 10.1016/j.molcel.2010.11.029 PG 16 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 701NF UT WOS:000285823900007 PM 21172654 ER PT J AU Tao, RD Coleman, MC Pennington, JD Ozden, O Park, SH Jiang, HY Kim, HS Flynn, CR Hill, S McDonald, WH Olivier, AK Spitz, DR Gius, D AF Tao, Randa Coleman, Mitchell C. Pennington, J. Daniel Ozden, Ozkan Park, Seong-Hoon Jiang, Haiyan Kim, Hyun-Seok Flynn, Charles Robb Hill, Salisha McDonald, W. Hayes Olivier, Alicia K. Spitz, Douglas R. Gius, David TI Sirt3-Mediated Deacetylation of Evolutionarily Conserved Lysine 122 Regulates MnSOD Activity in Response to Stress SO MOLECULAR CELL LA English DT Article ID DEPENDENT DEACETYLASE; SIR2 HOMOLOG; MITOCHONDRIA; CANCER; ACETYLATION; SUPEROXIDE; CELLS AB Genetic deletion of the mitochondrial deacetylase sirtuin-3 (Sirt3) results in increased mitochondrial superoxide, a tumor-permissive environment, and mammary tumor development. MnSOD contains a nutrient- and ionizing radiation (lR)-dependent reversible acetyl-lysine that is hyperacetylated in Sirt3(-/-) livers at 3 months of age. Livers of Sirt3(-/-) mice exhibit decreased MnSOD activity, but not immunoreactive protein, relative to wild-type livers. Reintroduction of wild-type but not deacetylation null Sirt3 into Sirt3(-/-) MEFs deacetylated lysine and restored MnSOD activity. Site-directed mutagenesis of MnSOD lysine 122 to an arginine, mimicking deacetylation (lenti-MnSOD(K122-R)), increased MnSOD activity when expressed in MnSOD(-/-) MEFs, suggesting acetylation directly regulates function. Furthermore, infection of Sirt3(-/-) MEFs with lenti-MnSOD(K122-R) inhibited in vitro immortalization by an oncogene (Ras), inhibited IR-induced genomic instability, and decreased mitochondrial superoxide. Finally, IR was unable to induce MnSOD deacetylation or activity in Sirt3(-/-) livers, and these irradiated livers displayed significant IR-induced cell damage and microvacuolization in their hepatocytes. C1 [Ozden, Ozkan; Park, Seong-Hoon; Jiang, Haiyan; Kim, Hyun-Seok; Gius, David] Vanderbilt Univ, Med Ctr, Dept Radiat Oncol, Nashville, TN 37232 USA. [Ozden, Ozkan; Park, Seong-Hoon; Jiang, Haiyan; Kim, Hyun-Seok; Gius, David] Vanderbilt Univ, Med Ctr, Dept Pediat, Nashville, TN 37232 USA. [Tao, Randa; Pennington, J. Daniel] Howard Hughes Med Inst, Bethesda, MD 20892 USA. [Tao, Randa; Pennington, J. Daniel] NCI, Radiat Oncol Branch, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. [Coleman, Mitchell C.; Spitz, Douglas R.] Univ Iowa, Holden Comprehens Canc Ctr, Dept Radiat Oncol, Free Rad & Radiat Biol Program, Iowa City, IA 52242 USA. [Olivier, Alicia K.] Univ Iowa, Carver Coll Med, Dept Pathol, Iowa City, IA 52242 USA. [Flynn, Charles Robb] Vanderbilt Univ, Dept Surg, Sch Med, Nashville, TN 37232 USA. [Hill, Salisha; McDonald, W. Hayes] Vanderbilt Univ, Mass Spectrometry Res Ctr, Sch Med, Nashville, TN 37232 USA. RP Gius, D (reprint author), Vanderbilt Univ, Med Ctr, Dept Radiat Oncol, Nashville, TN 37232 USA. EM david.gius@vanderbilt.edu RI Flynn, Charles/M-3895-2015; McDonald, W. Hayes/B-4109-2016 OI Flynn, Charles/0000-0002-3749-0598; McDonald, W. Hayes/0000-0002-3510-426X FU NCI [1R01CA152601-01]; DOD [BC093803]; SPORE [P50CA98131]; NIH; DOE [R01CA133114, T32CA078586, P30CA086862, DE-SC0000830]; [F30AG030839] FX D.G. is supported by 1R01CA152601-01 from the NCI, BC093803 from the DOD, and SPORE P50CA98131. D.R.S., A.K.O., and M.C.C. are supported by grants from the NIH and DOE (R01CA133114, T32CA078586, P30CA086862, and DE-SC0000830). J.D.P. is supported by F30AG030839. We thank Melissa Stauffer of Scientific Editing Solutions for editorial assistance. NR 19 TC 295 Z9 312 U1 2 U2 29 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 1097-2765 J9 MOL CELL JI Mol. Cell PD DEC 22 PY 2010 VL 40 IS 6 BP 893 EP 904 DI 10.1016/j.molcel.2010.12.013 PG 12 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 701NF UT WOS:000285823900008 PM 21172655 ER PT J AU Kaptchuk, TJ Friedlander, E Kelley, JM Sanchez, MN Kokkotou, E Singer, JP Kowalczykowski, M Miller, FG Kirsch, I Lembo, AJ AF Kaptchuk, Ted J. Friedlander, Elizabeth Kelley, John M. Sanchez, M. Norma Kokkotou, Efi Singer, Joyce P. Kowalczykowski, Magda Miller, Franklin G. Kirsch, Irving Lembo, Anthony J. TI Placebos without Deception: A Randomized Controlled Trial in Irritable Bowel Syndrome SO PLOS ONE LA English DT Article ID QUALITY-OF-LIFE; CLINICAL-TRIALS; END-POINT; METAANALYSIS; VALIDATION; DISORDERS; EFFICACY; BLIND AB Background: Placebo treatment can significantly influence subjective symptoms. However, it is widely believed that response to placebo requires concealment or deception. We tested whether open-label placebo (non-deceptive and non-concealed administration) is superior to a no-treatment control with matched patient-provider interactions in the treatment of irritable bowel syndrome (IBS). Methods: Two-group, randomized, controlled three week trial (August 2009-April 2010) conducted at a single academic center, involving 80 primarily female (70%) patients, mean age 47 +/- 18 with IBS diagnosed by Rome III criteria and with a score >= 150 on the IBS Symptom Severity Scale (IBS-SSS). Patients were randomized to either open-label placebo pills presented as "placebo pills made of an inert substance, like sugar pills, that have been shown in clinical studies to produce significant improvement in IBS symptoms through mind-body self-healing processes" or no-treatment controls with the same quality of interaction with providers. The primary outcome was IBS Global Improvement Scale (IBS-GIS). Secondary measures were IBS Symptom Severity Scale (IBS-SSS), IBS Adequate Relief (IBS-AR) and IBS Quality of Life (IBS-QoL). Findings: Open-label placebo produced significantly higher mean (+/- SD) global improvement scores (IBS-GIS) at both 11-day midpoint (5.2 +/- 1.0 vs. 4.0 +/- 1.1, p<.001) and at 21-day endpoint (5.0 +/- 1.5 vs. 3.9 +/- 1.3, p = .002). Significant results were also observed at both time points for reduced symptom severity (IBS-SSS, p = .008 and p = .03) and adequate relief (IBS-AR, p = .02 and p = .03); and a trend favoring open-label placebo was observed for quality of life (IBS-QoL) at the 21-day endpoint (p = .08). Conclusion: Placebos administered without deception may be an effective treatment for IBS. Further research is warranted in IBS, and perhaps other conditions, to elucidate whether physicians can benefit patients using placebos consistent with informed consent. C1 [Kaptchuk, Ted J.; Friedlander, Elizabeth; Sanchez, M. Norma; Kokkotou, Efi; Kowalczykowski, Magda; Lembo, Anthony J.] Harvard Univ, Beth Israel Deaconess Med Ctr, Sch Med, Boston, MA 02215 USA. [Kaptchuk, Ted J.; Singer, Joyce P.] Harvard Univ, Sch Med, Osher Res Ctr, Boston, MA 02215 USA. [Kelley, John M.] Endicott Coll, Dept Psychol, Beverly, MA USA. [Kelley, John M.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA 02215 USA. [Miller, Franklin G.] NIH, Dept Bioeth, Bethesda, MD 20892 USA. [Kirsch, Irving] Univ Hull, Dept Psychol, Kingston Upon Hull HU6 7RX, N Humberside, England. RP Kaptchuk, TJ (reprint author), Harvard Univ, Beth Israel Deaconess Med Ctr, Sch Med, Boston, MA 02215 USA. EM ted_kaptchuk@hms.harvard.edu FU National Center for Complementary and Alternative Medicine-NIH [K24 AT004095, R01 AT00402-01, R01AT004662] FX This study was partially supported by grant K24 AT004095, R01 AT00402-01 and R01AT004662 from National Center for Complementary and Alternative Medicine-NIH and in part from a gift from The Bernard Osher Foundation. The opinions expressed by the authors are their views alone and do not reflect the official views or policy of the National Center for Complementary and Alternative Medicine, National Institutes of Health, Public Health Service or the U.S. Department of Health and Human Services. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 37 TC 196 Z9 197 U1 9 U2 54 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 185 BERRY ST, STE 1300, SAN FRANCISCO, CA 94107 USA SN 1932-6203 J9 PLOS ONE JI PLoS One PD DEC 22 PY 2010 VL 5 IS 12 AR e15591 DI 10.1371/journal.pone.0015591 PG 7 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 698FG UT WOS:000285578000036 PM 21203519 ER PT J AU Levkovitz, L Yosef, N Gershengorn, MC Ruppin, E Sharan, R Oron, Y AF Levkovitz, Liron Yosef, Nir Gershengorn, Marvin C. Ruppin, Eytan Sharan, Roded Oron, Yoram TI A Novel HMM-Based Method for Detecting Enriched Transcription Factor Binding Sites Reveals RUNX3 as a Potential Target in Pancreatic Cancer Biology SO PLOS ONE LA English DT Article ID T-CELL DEVELOPMENT; GENE-EXPRESSION; PRECURSOR CELLS; GASTRIC-CANCER; GROWTH; METHYLATION; METASTASIS; INHIBITION; DISCOVERY AB Background: Pancreatic adenocarcinoma (PAC) is one of the most intractable malignancies. In order to search for potential new therapeutic targets, we relied on computational methods aimed at identifying transcription factor binding sites (TFBSs) over-represented in the promoter regions of genes differentially expressed in PAC. Though many computational methods have been implemented to accomplish this, none has gained overall acceptance or produced proven novel targets in PAC. To this end we have developed DEMON, a novel method for motif detection. Methodology: DEMON relies on a hidden Markov model to score the appearance of sequence motifs, taking into account all potential sites in a promoter of potentially varying binding affinities. We demonstrate DEMON's accuracy on simulated and real data sets. Applying DEMON to PAC-related data sets identifies the RUNX family as highly enriched in PAC-related genes. Using a novel experimental paradigm to distinguish between normal and PAC cells, we find that RUNX3 mRNA (but not RUNX1 or RUNX2 mRNAs) exhibits time-dependent increases in normal but not in PAC cells. These increases are accompanied by changes in mRNA levels of putative RUNX gene targets. Conclusions: The integrated application of DEMON and a novel differentiation system led to the identification of a single family member, RUNX3, which together with four of its putative targets showed a robust response to a differentiation stimulus in healthy cells, whereas this regulatory mechanism was absent in PAC cells, emphasizing RUNX3 as a promising target for further studies. C1 [Levkovitz, Liron; Ruppin, Eytan; Oron, Yoram] Tel Aviv Univ, Sackler Fac Med, Dept Physiol & Pharmacol, IL-69978 Tel Aviv, Israel. [Levkovitz, Liron; Yosef, Nir; Ruppin, Eytan; Sharan, Roded] Tel Aviv Univ, Sch Comp Sci, IL-69978 Tel Aviv, Israel. [Gershengorn, Marvin C.] NIDDK, Clin Endocrinol Branch, NIH, Bethesda, MD USA. RP Levkovitz, L (reprint author), Tel Aviv Univ, Sackler Fac Med, Dept Physiol & Pharmacol, IL-69978 Tel Aviv, Israel. EM roded@post.tau.ac.il; medfair@post.tau.ac.il FU Era-Net pathogenomics; Israel Cancer Association FX This work was supported by an Era-Net pathogenomics grant to ER and RS, and Israel Cancer Association grant to ER, RS and YO. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 36 TC 2 Z9 2 U1 0 U2 2 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 185 BERRY ST, STE 1300, SAN FRANCISCO, CA 94107 USA SN 1932-6203 J9 PLOS ONE JI PLoS One PD DEC 22 PY 2010 VL 5 IS 12 AR e14423 DI 10.1371/journal.pone.0014423 PG 9 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 698FG UT WOS:000285578000018 PM 21203558 ER PT J AU Miller, TW Isenberg, JS Shih, HB Wang, YC Roberts, DD AF Miller, Thomas W. Isenberg, Jeff S. Shih, Hubert B. Wang, Yichen Roberts, David D. TI Amyloid-beta Inhibits No-cGMP Signaling in a CD36-and CD47-Dependent Manner SO PLOS ONE LA English DT Article ID SOLUBLE GUANYLATE-CYCLASE; ISCHEMIC TISSUE SURVIVAL; LONG-TERM POTENTIATION; NITRIC-OXIDE SYNTHASE; ALZHEIMERS-DISEASE; PLATELET-AGGREGATION; CELL RESPONSES; SMOOTH-MUSCLE; MICROGLIAL PHAGOCYTOSIS; PRECURSOR PROTEIN AB Amyloid-beta interacts with two cell surface receptors, CD36 and CD47, through which the matricellular protein thrombospondin-1 inhibits soluble guanylate cyclase activation. Here we examine whether amyloid-beta shares this inhibitory activity. Amyloid-beta inhibited both drug and nitric oxide-mediated activation of soluble guanylate cyclase in several cell types. Known cGMP-dependent functional responses to nitric oxide in platelets and vascular smooth muscle cells were correspondingly inhibited by amyloid-beta. Functional interaction of amyloid-beta with the scavenger receptor CD36 was indicated by inhibition of free fatty acid uptake via this receptor. Both soluble oligomer and fibrillar forms of amyloid-beta were active. In contrast, amyloid-beta did not compete with the known ligand SIRP alpha for binding to CD47. However, both receptors were necessary for amyloid-beta to inhibit cGMP accumulation. These data suggest that amyloid-beta interaction with CD36 induces a CD47-dependent signal that inhibits soluble guanylate cyclase activation. Combined with the pleiotropic effects of inhibiting free fatty acid transport via CD36, these data provides a molecular mechanism through which amyloid-beta can contribute to the nitric oxide signaling deficiencies associated with Alzheimer's disease. C1 [Miller, Thomas W.; Isenberg, Jeff S.; Shih, Hubert B.; Wang, Yichen; Roberts, David D.] NCI, Pathol Lab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. [Isenberg, Jeff S.] Univ Pittsburgh, Sch Med, Dept Med, Pittsburgh, PA USA. [Shih, Hubert B.] NIH, Howard Hughes Med Inst, Res Scholars Program, Bethesda, MD 20892 USA. RP Miller, TW (reprint author), NCI, Pathol Lab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. EM droberts@helix.nih.gov RI Roberts, David/A-9699-2008; Miller, Thomas/G-1215-2011 OI Roberts, David/0000-0002-2481-2981; Miller, Thomas/0000-0001-8645-2785 FU National Institutes of Health (NIH), National Cancer Institute, Center for Cancer Research [CA128616]; Howard Hughes Medical Institute-NIH FX This work was supported by the Intramural Research Program of the National Institutes of Health (NIH), National Cancer Institute, Center for Cancer Research (D. D. R.), NIH grant CA128616 (J.S.I.) and by the Howard Hughes Medical Institute-NIH Research Scholars Program (H. B. S.). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 60 TC 15 Z9 15 U1 0 U2 4 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA SN 1932-6203 J9 PLOS ONE JI PLoS One PD DEC 22 PY 2010 VL 5 IS 12 AR e15686 DI 10.1371/journal.pone.0015686 PG 10 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 698FG UT WOS:000285578000045 PM 21203512 ER PT J AU Teferedegne, B Murata, H Quinones, M Peden, K Lewis, AM AF Teferedegne, Belete Murata, Haruhiko Quinones, Mariam Peden, Keith Lewis, Andrew M., Jr. TI Patterns of microRNA Expression in Non-Human Primate Cells Correlate with Neoplastic Development In Vitro SO PLOS ONE LA English DT Article ID HUMAN BREAST-CANCER; HUMAN TUMOR-CELLS; DOWN-REGULATION; VERO CELLS; MESENCHYMAL TRANSITION; EPITHELIAL-CELLS; NKG2D; METASTASIS; TRANSFORMATION; PROGRESSION AB MicroRNAs (miRNAs) are small noncoding RNAs that negatively regulate gene expression post-transcriptionally. They play a critical role in developmental and physiological processes and have been implicated in the pathogenesis of several diseases including cancer. To identify miRNA signatures associated with different stages of neoplastic development, we examined the expression profile of 776 primate miRNAs in VERO cells (a neoplastically transformed cell line being used for the manufacture of viral vaccines), progenitor primary African green monkey kidney (pAGMK) cells, and VERO cell derivatives: spontaneously immortalized, non-tumorigenic, low-passage VERO cells (10-87 LP); tumorigenic, high-passage VERO cells (10-87 HP); and a cell line (10-87 T) derived from a 10-87 HP cell tumor xenograft in athymic nude mice. When compared with pAGMK cells, the majority of miRNAs were expressed at lower levels in 10-87 LP, 10-87 HP, and 10-87 T cells. We identified 10 up-regulated miRNAs whose level of expression correlated with VERO cell evolution from a non-tumorigenic phenotype to a tumorigenic phenotype. The overexpression of miR-376a and the polycistronic cluster of miR-376a, miR-376b and miR-376c conferred phenotypic changes to the non-tumorigenic 10-87 LP cells that mimic the tumorigenic 10-87 HP cells. Thirty percent of miRNAs that were components of the identified miRNAs in our spontaneously transformed AGMK cell model are also dysregulated in a variety of human tumors. These results may prove to be relevant to the biology of neoplastic development. In addition, one or more of these miRNAs could be biomarkers for the expression of a tumorigenic phenotype. C1 [Teferedegne, Belete; Murata, Haruhiko; Lewis, Andrew M., Jr.] US FDA, Lab DNA Viruses, Div Viral Prod, Ctr Biol Evaluat & Res, Bethesda, MD 20014 USA. [Peden, Keith] US FDA, Lab Retrovirus Res, Div Viral Prod, Ctr Biol Evaluat & Res, Bethesda, MD 20014 USA. [Quinones, Mariam] NIH, Bioinformat & Computat Biosci Branch, Bethesda, MD 20892 USA. RP Teferedegne, B (reprint author), US FDA, Lab DNA Viruses, Div Viral Prod, Ctr Biol Evaluat & Res, Bethesda, MD 20014 USA. EM andrew.lewis@fda.hhs.gov FU Division of Microbiology and Infectious Diseases (DMID); National Institute of Allergy and Infectious Diseases (NIAID) through Biologics Evaluation and Research (CBER); Food and Drug Administration (FDA) FX This work is partially supported by a contract from the Division of Microbiology and Infectious Diseases (DMID), National Institute of Allergy and Infectious Diseases (NIAID) through an interagency agreement with Center for Biologics Evaluation and Research (CBER), Food and Drug Administration (FDA). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 78 TC 13 Z9 13 U1 0 U2 2 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA SN 1932-6203 J9 PLOS ONE JI PLoS One PD DEC 22 PY 2010 VL 5 IS 12 AR e14416 DI 10.1371/journal.pone.0014416 PG 12 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 698FG UT WOS:000285578000017 PM 21203544 ER PT J AU Stoye, JP Silverman, RH Boucher, CA Le Grice, SFJ AF Stoye, Jonathan P. Silverman, Robert H. Boucher, Charles A. Le Grice, Stuart F. J. TI The xenotropic murine leukemia virus-related retrovirus debate continues at first international workshop SO RETROVIROLOGY LA English DT Review ID CHRONIC-FATIGUE-SYNDROME; PROSTATE-CANCER; XMRV INFECTION; BLOOD; SEQUENCES; FAILURE; CELLS; GENE AB The 1(st) International Workshop on Xenotropic Murine Leukemia Virus-Related Retrovirus (XMRV), co-sponsored by the National Institutes of Health, The Department of Health and Human Services and Abbott Diagnostics, was convened on September 7/8, 2010 on the NIH campus, Bethesda, MD. Attracting an international audience of over 200 participants, the 2-day event combined a series of plenary talks with updates on different aspects of XMRV research, addressing basic gammaretrovirus biology, host response, association of XMRV with chronic fatigue syndrome and prostate cancer, assay development and epidemiology. The current status of XMRV research, concerns among the scientific community and suggestions for future actions are summarized in this meeting report. C1 [Le Grice, Stuart F. J.] NCI, HIV Drug Resistance Program, Frederick, MD 21702 USA. [Silverman, Robert H.] Cleveland Clin, Lerner Res Inst, Dept Canc Biol, Cleveland, OH 44195 USA. [Stoye, Jonathan P.] Natl Inst Med Res, MRC, London NW7 1AA, England. [Boucher, Charles A.] Univ Med Ctr Rotterdam, Dept Virol, Erasmus MC, Rotterdam, Netherlands. RP Le Grice, SFJ (reprint author), NCI, HIV Drug Resistance Program, Frederick, MD 21702 USA. EM legrices@mail.nih.gov FU Medical Research Council [MC_U117512710] NR 31 TC 9 Z9 9 U1 0 U2 2 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1742-4690 J9 RETROVIROLOGY JI Retrovirology PD DEC 22 PY 2010 VL 7 AR 113 DI 10.1186/1742-4690-7-113 PG 10 WC Virology SC Virology GA 708WN UT WOS:000286395100001 PM 21176195 ER PT J AU Evans, G Austin, F AF Evans, Greg Austin, Finley TI Collaborations Among Academia, Government, and Industry in the Diagnostics Space: Barriers and Some Ideas for Solutions SO SCIENCE TRANSLATIONAL MEDICINE LA English DT Editorial Material AB The development and commercialization of diagnostic assays is distinct from that of therapeutic drugs in many important respects; for example, there are more variable regulatory requirements and reduced outside investments for diagnostics. The diagnostics industry has a pro-collaborative stance, because there is considerable mutual benefit in working in partnership with university or government researchers. However, there are substantial barriers to industry-academic collaborations. A Clinical and Translational Science Awards Industry Forum titled "Promoting Efficient and Effective Collaborations Among Academia, Government, and Industry" was held in February 2010, and a session at this forum was organized to list some of the most important barriers to diagnostics development and to discuss some possible solutions. C1 [Evans, Greg] NCI, NIH, US Dept Hlth & Human Serv, Small Business Innovat Res Dev Ctr, Bethesda, MD 20892 USA. [Austin, Finley] Hoffman La Roche, Pharma Res & Early Dev, Translat Res Sci, Nutley, NJ 07110 USA. RP Evans, G (reprint author), NCI, NIH, US Dept Hlth & Human Serv, Small Business Innovat Res Dev Ctr, Bethesda, MD 20892 USA. EM evansgl@mail.nih.gov FX This project was funded in whole or in part with Federal funds from the National Center for Research Resources, NIH, through the CTSA program, which is part of the Roadmap Initiative, Re-engineering the Clinical Research Enterprise. The manuscript was approved by the CTSA Consortium Publications Committee. NR 0 TC 2 Z9 2 U1 2 U2 5 PU AMER ASSOC ADVANCEMENT SCIENCE PI WASHINGTON PA 1200 NEW YORK AVE, NW, WASHINGTON, DC 20005 USA SN 1946-6234 J9 SCI TRANSL MED JI Sci. Transl. Med. PD DEC 22 PY 2010 VL 2 IS 63 AR 63mr3 DI 10.1126/scitranslmed.3001633 PG 3 WC Cell Biology; Medicine, Research & Experimental SC Cell Biology; Research & Experimental Medicine GA 735UK UT WOS:000288444900006 PM 21178133 ER PT J AU Portilla, LM Evans, G Eng, B Fadem, TJ AF Portilla, Lili M. Evans, Greg Eng, Benjamin Fadem, Terry J. TI Advancing Translational Research Collaborations SO SCIENCE TRANSLATIONAL MEDICINE LA English DT Article AB In February 2010, the U. S. National Institutes of Health (NIH) sponsored a national Clinical and Translational Science Awards forum titled "Promoting Efficient and Effective Collaborations among Academia, Government and Industry." This forum brought together a broad set of stakeholders who were charged with developing a path for promoting such partnerships. Here, we describe key issues discussed at the forum and plans for moving forward with this ambitious agenda. C1 [Portilla, Lili M.] NIH, Natl Ctr Res Resources, Bethesda, MD 20892 USA. [Evans, Greg] NCI, Small Business Innovat Res Dev Ctr, NIH, Bethesda, MD 20892 USA. [Eng, Benjamin] Pfizer Inc, Med Acad, New York, NY 10017 USA. [Fadem, Terry J.] Univ Penn, Sch Med, Philadelphia, PA 19104 USA. RP Portilla, LM (reprint author), NIH, Natl Ctr Res Resources, Bethesda, MD 20892 USA. EM portilll@mail.nih.gov FU NCRR; NIH, through the CTSA FX This project has been funded in whole or in part with U.S. federal funds from NCRR as well as NIH, through the CTSA, which is part of the Roadmap Initiative, Re-Engineering the Clinical Research Enterprise. The manuscript was approved by the CTSA Consortium Publications Committee. NR 13 TC 4 Z9 4 U1 0 U2 6 PU AMER ASSOC ADVANCEMENT SCIENCE PI WASHINGTON PA 1200 NEW YORK AVE, NW, WASHINGTON, DC 20005 USA SN 1946-6234 J9 SCI TRANSL MED JI Sci. Transl. Med. PD DEC 22 PY 2010 VL 2 IS 63 AR 63cm30 DI 10.1126/scitranslmed.3001636 PG 4 WC Cell Biology; Medicine, Research & Experimental SC Cell Biology; Research & Experimental Medicine GA 735UK UT WOS:000288444900002 PM 21178130 ER PT J AU Mozaffarian, D Cao, HM King, IB Lemaitre, RN Song, XL Siscovick, DS Hotamisligil, GS AF Mozaffarian, Dariush Cao, Haiming King, Irena B. Lemaitre, Rozenn N. Song, Xiaoling Siscovick, David S. Hotamisligil, Goekhan S. TI Trans-Palmitoleic Acid, Metabolic Risk Factors, and New-Onset Diabetes in U.S. Adults A Cohort Study SO ANNALS OF INTERNAL MEDICINE LA English DT Article ID CONJUGATED LINOLEIC-ACID; DE-NOVO LIPOGENESIS; NONFATAL MYOCARDIAL-INFARCTION; INSULIN-RESISTANCE SYNDROME; SERUM-CHOLESTEROL ESTERS; ISCHEMIC-HEART-DISEASE; C-REACTIVE PROTEIN; DAIRY FAT INTAKE; ADIPOSE-TISSUE; HIGH-CARBOHYDRATE AB Background: Palmitoleic acid (cis-16:1n-7), which is produced by endogenous fat synthesis, has been linked to both beneficial and deleterious metabolic effects, potentially confounded by diverse determinants and tissue sources of endogenous production. Trans-palmitoleate (trans-16:1n-7) represents a distinctly exogenous source of 16:1n-7, unconfounded by endogenous synthesis or its determinants, that may be uniquely informative. Objective: To investigate whether circulating trans-palmitoleate is independently related to lower metabolic risk and incident type 2 diabetes. Design: Prospective cohort study from 1992 to 2006. Setting: Four U.S. communities. Patients: 3736 adults in the Cardiovascular Health Study. Measurements: Anthropometric characteristics and levels of plasma phospholipid fatty acids, blood lipids, inflammatory markers, and glucose-insulin measured at baseline in 1992 and dietary habits measured 3 years earlier. Multivariate-adjusted models were used to investigate how demographic, clinical, and lifestyle factors independently related to plasma phospholipid trans-palmitoleate; how trans-palmitoleate related to major metabolic risk factors; and how trans-palmitoleate related to new-onset diabetes (304 incident cases). Findings were validated for metabolic risk factors in an independent cohort of 327 women. Results: In multivariate analyses, whole-fat dairy consumption was most strongly associated with higher trans-palmitoleate levels. Higher trans-palmitoleate levels were associated with slightly lower adiposity and, independently, with higher high-density lipoprotein cholesterol levels (1.9% across quintiles; P = 0.040), lower triglyceride levels (-19.0%; P < 0.001), a lower total cholesterol-HDL cholesterol ratio (-4.7%; P < 0.001), lower C-reactive protein levels (-13.8%; P = 0.05), and lower insulin resistance (-16.7%, P < 0.001). Trans-palmitoleate was also associated with a substantially lower incidence of diabetes, with multivariate hazard ratios of 0.41 (95% CI, 0.27 to 0.64) and 0.38 (CI, 0.24 to 0.62) in quintiles 4 and 5 versus quintile 1 (P for trend < 0.001). Findings were independent of estimated dairy consumption or other fatty acid dairy biomarkers. Protective associations with metabolic risk factors were confirmed in the validation cohort. Limitation: Results could be affected by measurement error or residual confounding. Conclusion: Circulating trans-palmitoleate is associated with lower insulin resistance, presence of atherogenic dyslipidemia, and incident diabetes. Our findings may explain previously observed metabolic benefits of dairy consumption and support the need for detailed further experimental and clinical investigation. C1 [Mozaffarian, Dariush] Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA. Harvard Univ, Sch Med, Brigham & Womens Hosp, Boston, MA 02115 USA. NIH, Bethesda, MD 20892 USA. Univ New Mexico, Albuquerque, NM 87131 USA. Fred Hutchinson Canc Res Ctr, Seattle, WA 98109 USA. Univ Washington, Seattle, WA 98195 USA. RP Mozaffarian, D (reprint author), Harvard Univ, Sch Publ Hlth, 665 Huntington Ave,Bldg 2-319, Boston, MA 02115 USA. EM dmozaffa@hsph.harvard.edu RI Cao, Haiming/P-4634-2016 FU National Heart, Lung, and Blood Institute; National Institute of Diabetes and Digestive and Kidney Diseases of the National Institutes of Health [R01-HL085710, DK064360, DK71507-04, N01-HC-35129, N01-HC-45133, N01-HC-75150, N01-HC-85079, -85086, N01-HC-15103, N01-HC-55222, U01-HL080295]; Searle Scholar Award FX National Heart, Lung, and Blood Institute and National Institute of Diabetes and Digestive and Kidney Diseases of the National Institutes of Health.; By the National Heart, Lung, and Blood Institute and National Institute of Diabetes and Digestive and Kidney Diseases of the National Institutes of Health (grants R01-HL085710, DK064360, and DK71507-04 and grants N01-HC-35129, N01-HC-45133, N01-HC-75150, N01-HC-85079 through -85086, N01-HC-15103, N01-HC-55222, and U01-HL080295 for the CHS), with additional contributions from the National Institutes of Health Office of Dietary Supplements and National Institute of Neurological Disorders and Stroke. A subset of additional fatty acid measurements was supported by a Searle Scholar Award. NR 69 TC 128 Z9 131 U1 3 U2 18 PU AMER COLL PHYSICIANS PI PHILADELPHIA PA INDEPENDENCE MALL WEST 6TH AND RACE ST, PHILADELPHIA, PA 19106-1572 USA SN 0003-4819 EI 1539-3704 J9 ANN INTERN MED JI Ann. Intern. Med. PD DEC 21 PY 2010 VL 153 IS 12 BP 790 EP + DI 10.7326/0003-4819-153-12-201012210-00005 PG 11 WC Medicine, General & Internal SC General & Internal Medicine GA 696PL UT WOS:000285453700002 PM 21173413 ER PT J AU Lichtenberg, J Kurz, K Liang, XY Al-Ouran, R Neiman, L Nau, LJ Welch, JD Jacox, E Bitterman, T Ecker, K Elnitski, L Drews, F Lee, SS Welch, LR AF Lichtenberg, Jens Kurz, Kyle Liang, Xiaoyu Al-Ouran, Rami Neiman, Lev Nau, Lee J. Welch, Joshua D. Jacox, Edwin Bitterman, Thomas Ecker, Klaus Elnitski, Laura Drews, Frank Lee, Stephen Sauchi Welch, Lonnie R. TI WordSeeker: concurrent bioinformatics software for discovering genome-wide patterns and word-based genomic signatures SO BMC BIOINFORMATICS LA English DT Article; Proceedings Paper CT 11th Annual Bioinformatics Open Source Conference (BOSC) CY JUL 09-10, 2010 CL Boston, MA ID FACTOR-BINDING SITES; SEQUENCES; MOTIFS; GENES AB Background: An important focus of genomic science is the discovery and characterization of all functional elements within genomes. In silico methods are used in genome studies to discover putative regulatory genomic elements (called words or motifs). Although a number of methods have been developed for motif discovery, most of them lack the scalability needed to analyze large genomic data sets. Methods: This manuscript presents WordSeeker, an enumerative motif discovery toolkit that utilizes multi-core and distributed computational platforms to enable scalable analysis of genomic data. A controller task coordinates activities of worker nodes, each of which (1) enumerates a subset of the DNA word space and (2) scores words with a distributed Markov chain model. Results: A comprehensive suite of performance tests was conducted to demonstrate the performance, speedup and efficiency of WordSeeker. The scalability of the toolkit enabled the analysis of the entire genome of Arabidopsis thaliana; the results of the analysis were integrated into The Arabidopsis Gene Regulatory Information Server (AGRIS). A public version of WordSeeker was deployed on the Glenn cluster at the Ohio Supercomputer Center. Conclusion: WordSeeker effectively utilizes concurrent computing platforms to enable the identification of putative functional elements in genomic data sets. This capability facilitates the analysis of the large quantity of sequenced genomic data. C1 [Lichtenberg, Jens; Kurz, Kyle; Liang, Xiaoyu; Al-Ouran, Rami; Neiman, Lev; Nau, Lee J.; Welch, Joshua D.; Ecker, Klaus; Drews, Frank; Welch, Lonnie R.] Ohio Univ, Sch EECS, Bioinformat Lab, Athens, OH 45701 USA. [Jacox, Edwin] Dev Biol Inst Marseille, F-13009 Marseille, France. [Bitterman, Thomas] Ohio Supercomp Ctr, Cyberinfrastruct Grp, Columbus, OH 43212 USA. [Elnitski, Laura] NHGRI, Genom Funct Anal Sect, NIH, Bethesda, MD 20892 USA. [Lee, Stephen Sauchi] Univ Idaho, Dept Stat, Moscow, ID 83844 USA. [Welch, Lonnie R.] Ohio Univ, Biomed Engn Program, Athens, OH 45701 USA. [Welch, Lonnie R.] Ohio Univ, Mol & Cellular Biol Program, Athens, OH 45701 USA. RP Lichtenberg, J (reprint author), Ohio Univ, Sch EECS, Bioinformat Lab, Athens, OH 45701 USA. EM lichtenj@ohio.edu FU Intramural NIH HHS NR 35 TC 2 Z9 2 U1 1 U2 2 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1471-2105 J9 BMC BIOINFORMATICS JI BMC Bioinformatics PD DEC 21 PY 2010 VL 11 SU 12 AR S6 DI 10.1186/1471-2105-11-S12-S6 PG 8 WC Biochemical Research Methods; Biotechnology & Applied Microbiology; Mathematical & Computational Biology SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Mathematical & Computational Biology GA 759DA UT WOS:000290219600006 PM 21210985 ER PT J AU Inoue, M Yasuda, K Uemura, H Yasaka, N Inoue, H Sei, Y Horikoshi, N Fukuma, T AF Inoue, Masahiro Yasuda, Kouichi Uemura, Haruki Yasaka, Natsumi Inoue, Hiroshi Sei, Yoshitatsu Horikoshi, Nobuo Fukuma, Toshihide TI Phosphorylation-Dependent Protein Interaction with Trypanosoma brucei 14-3-3 Proteins that Display Atypical Target Recognition SO PLOS ONE LA English DT Article ID 14-3-3-PROTEINS; BINDING; ISOFORMS; CYTOKINESIS; SPECIFICITY; GENOME; KINASE; ZETA AB Background: The 14-3-3 proteins are structurally conserved throughout eukaryotes and participate in protein kinase signaling. All 14-3-3 proteins are known to bind to evolutionally conserved phosphoserine-containing motifs (modes 1 and/or 2) with high affinity. In Trypanosoma brucei, 14-3-3I and II play pivotal roles in motility, cytokinesis and the cell cycle. However, none of the T. brucei 14-3-3 binding proteins have previously been documented. Methodology/Principal Findings: Initially we showed that T. brucei 14-3-3 proteins exhibit far lower affinity to those peptides containing RSxpSxP (mode 1) and RxY/FxpSxP (mode 2) (where x is any amino acid residue and pS is phosphoserine) than human 14-3-3 proteins, demonstrating the atypical target recognition by T. brucei 14-3-3 proteins. We found that the putative T. brucei protein phosphatase 2C (PP2c) binds to T. brucei 14-3-3 proteins utilizing its mode 3 motif (-pS/pTx(1-2)-COOH, where x is not Pro). We constructed eight chimeric PP2c proteins replacing its authentic mode 3 motif with potential mode 3 sequences found in Trypanosoma brucei genome database, and tested their binding. As a result, T. brucei 14-3-3 proteins interacted with three out of eight chimeric proteins including two with high affinity. Importantly, T. brucei 14-3-3 proteins co-immunoprecipitated with an uncharacterized full-length protein containing identified high-affinity mode 3 motif, suggesting that both proteins form a complex in vivo. In addition, a synthetic peptide derived from this mode 3 motif binds to T. brucei 14-3-3 proteins with high affinity. Conclusion/Significance: Because of the atypical target recognition of T. brucei 14-3-3 proteins, no 14-3-3-binding proteins have been successfully identified in T. brucei until now whereas over 200 human 14-3-3-binding proteins have been identified. This report describes the first discovery of the T. brucei 14-3-3-binding proteins and their binding motifs. The high-affinity phosphopeptide will be a powerful tool to identify novel T. brucei 14-3-3-binding proteins. C1 [Inoue, Masahiro; Yasuda, Kouichi; Yasaka, Natsumi; Inoue, Hiroshi; Fukuma, Toshihide] Kurume Univ, Sch Med, Dept Infect Med, Div Eukaryot Microbiol, Kurume, Fukuoka 830, Japan. [Uemura, Haruki] Nagasaki Univ, Inst Trop Med, Dept Protozool, Nagasaki 852, Japan. [Sei, Yoshitatsu] NIDDK, Gastroenterol Sect, Digest Dis Branch, Bethesda, MD USA. [Horikoshi, Nobuo] SW Texas State Univ, Div Mol Radiat Biol, Dept Radiat Oncol, Sch Med, Dallas, TX USA. RP Inoue, M (reprint author), Kurume Univ, Sch Med, Dept Infect Med, Div Eukaryot Microbiol, Kurume, Fukuoka 830, Japan. EM inouedna@med.kurume-u.ac.jp FU Ministry of Education, Science, Sports and Culture, Grant-in-Aid for Scientific Research [2009, 20590434]; Institute of Tropical Medicine, Nagasaki University [2008-20-D-2, 2009-21-E-8]; Ishibashi Foundation for the Promotion of Science FX This research was supported by the Ministry of Education, Science, Sports and Culture, Grant-in-Aid for Scientific Research (C), 2009, 20590434, by the Cooperative Research Grant(s) (2008-20-D-2, 2009-21-E-8, 9) of the Institute of Tropical Medicine, Nagasaki University, and by a grant from the Ishibashi Foundation for the Promotion of Science. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 23 TC 5 Z9 5 U1 0 U2 4 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 185 BERRY ST, STE 1300, SAN FRANCISCO, CA 94107 USA SN 1932-6203 J9 PLOS ONE JI PLoS One PD DEC 21 PY 2010 VL 5 IS 12 AR e15566 DI 10.1371/journal.pone.0015566 PG 8 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 698EY UT WOS:000285576900032 PM 21203569 ER PT J AU Khodyreva, SN Prasad, R Ilina, ES Sukhanova, MV Kutuzov, MM Liu, Y Hou, EW Wilson, SH Lavrik, OI AF Khodyreva, S. N. Prasad, R. Ilina, E. S. Sukhanova, M. V. Kutuzov, M. M. Liu, Y. Hou, E. W. Wilson, S. H. Lavrik, O. I. TI Apurinic/apyrimidinic (AP) site recognition by the 5 '-dRP/AP lyase in poly(ADP-ribose) polymerase-1 (PARP-1) SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE Schiff base; apurinic/apyrimidinic site-binding protein ID BASE-EXCISION-REPAIR; DNA-REPAIR; ABASIC SITES; MAMMALIAN-CELLS; BETA; ENDONUCLEASE; DAMAGE; PROTEINS; CLEAVAGE; ENZYMES AB The capacity of human poly(ADP-ribose) polymerase-1 (PARP-1) to interact with intact apurinic/apyrimidinic (AP) sites in DNA has been demonstrated. In cell extracts, sodium borohydride reduction of the PARP-1/AP site DNA complex resulted in covalent cross-linking of PARP-1 to DNA; the identity of cross-linked PARP-1 was confirmed by mass spectrometry. Using purified human PARP-1, the specificity of PARP-1 binding to AP site-containing DNA was confirmed in competition binding experiments. PARP-1 was only weakly activated to conduct poly(ADP-ribose) synthesis upon binding to AP site-containing DNA, but was strongly activated for poly (ADP-ribose) synthesis upon strand incision by AP endonuclease 1 (APE1). By virtue of its binding to AP sites, PARP-1 could be poised for its role in base excision repair, pending DNA strand incision by APE1 or the 5'-dRP/AP lyase activity in PARP-1. C1 [Khodyreva, S. N.; Ilina, E. S.; Sukhanova, M. V.; Kutuzov, M. M.; Lavrik, O. I.] Russian Acad Sci, Inst Chem Biol & Fundamental Med, Siberian Branch, Novosibirsk, Russia. [Prasad, R.; Liu, Y.; Hou, E. W.; Wilson, S. H.] NIEHS, NIH, Res Triangle Pk, NC 27709 USA. RP Lavrik, OI (reprint author), Russian Acad Sci, Inst Chem Biol & Fundamental Med, Siberian Branch, Novosibirsk, Russia. EM lavrik@niboch.nsc.ru RI Kutuzov, Mikhail/G-4239-2013; Ilina , Ekaterina/G-4224-2013; Khodyreva, Svetlana/G-4659-2013; Lavrik, Olga /G-4641-2013 FU Russian Foundation for Basic Research [10-04-01083, 09-04-93106, 09-04-91320 (HRJRG-102)]; RAS; National Institutes of Health, National Institute of Environmental Health Sciences [Z01-ES050158, Z01-ES050159]; [02.740.11.0079] FX We thank Dr. Yu. Gerasimova (Institute of Chemical Biology and Fundamental Medicine, SB RAS) for recording the MALDI-TOF-MS spectra. The authors also thank Bonnie Mesmer for assistance in manuscript preparation. This work was supported in part by the Russian Foundation for Basic Research [Projects 10-04-01083, 09-04-93106, and 09-04-91320 (HRJRG-102)], the Program of RAS "Molecular and Cellular Biology," and State Contract 02.740.11.0079. This work also was supported in part by Research Projects Z01-ES050158 and Z01-ES050159 in the Intramural Research Program of the National Institutes of Health, National Institute of Environmental Health Sciences. NR 38 TC 48 Z9 53 U1 0 U2 7 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD DEC 21 PY 2010 VL 107 IS 51 BP 22090 EP 22095 DI 10.1073/pnas.1009182107 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 697OB UT WOS:000285521800031 PM 21127267 ER PT J AU Song, KM Bolton, DL Wilson, RL Camp, JV Bao, SR Mattapallil, JJ Herzenberg, LA Herzenberg, LA Andrews, CA Sadoff, JC Goudsmit, J Pau, MG Seder, RA Kozlowski, PA Nabel, GJ Roederer, M Rao, SS AF Song, Kaimei Bolton, Diane L. Wilson, Robert L. Camp, Jeremy V. Bao, Saran Mattapallil, Joseph J. Herzenberg, Leonore A. Herzenberg, Leonard A. Andrews, Charla A. Sadoff, Jerald C. Goudsmit, Jaap Pau, Maria Grazia Seder, Robert A. Kozlowski, Pamela A. Nabel, Gary J. Roederer, Mario Rao, Srinivas S. TI Genetic immunization in the lung induces potent local and systemic immune responses SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE mucosal responses; tuberculosis; platform immunization ID NEUTRALIZING ANTIBODIES; VACCINE VECTORS; RHESUS-MONKEYS; VIRUS; PROTECTION; INFLUENZA; IMMUNOGENICITY; INTERFERON; POULTRY; FERRETS AB Successful vaccination against respiratory infections requires elicitation of high levels of potent and durable humoral and cellular responses in the lower airways. To accomplish this goal, we used a fine aerosol that targets the entire lung surface through normal respiration to deliver replication-incompetent recombinant adenoviral vectors expressing gene products from several infectious pathogens. We show that this regimen induced remarkably high and stable lung T-cell responses in nonhuman primates and that it also generated systemic and respiratory tract humoral responses of both IgA and IgG isotypes. Moreover, strong immunogenicity was achieved even in animals with preexisting antiadenoviral immunity, overcoming a critical hurdle to the use of these vectors in humans, who commonly are immune to adenoviruses. The immunogenicity profile elicited with this regimen, which is distinct from either intramuscular or intranasal delivery, has highly desirable properties for protection against respiratory pathogens. We show that it can be used repeatedly to generate mucosal humoral, CD4, and CD8 T-cell responses and as such may be applicable to other mucosally transmitted pathogens such as HIV. Indeed, in a lethal challenge model, we show that aerosolized recombinant adenoviral immunization completely protects ferrets against H5N1 highly pathogenic avian influenza virus. Thus, genetic immunization in the lung offers a powerful platform approach to generating protective immune responses against respiratory pathogens. C1 Stanford Univ, Dept Genet, Stanford, CA 94305 USA. [Song, Kaimei; Bolton, Diane L.; Bao, Saran; Andrews, Charla A.; Seder, Robert A.; Nabel, Gary J.; Roederer, Mario; Rao, Srinivas S.] NIAID, Vaccine Res Ctr, NIH, Bethesda, MD 20892 USA. [Wilson, Robert L.; Camp, Jeremy V.; Kozlowski, Pamela A.] Louisiana State Univ, Hlth Sci Ctr, Gene Therapy Program, New Orleans, LA 70803 USA. [Wilson, Robert L.; Camp, Jeremy V.; Kozlowski, Pamela A.] Louisiana State Univ, Hlth Sci Ctr, Dept Microbiol Immunol & Parasitol, New Orleans, LA 70803 USA. [Mattapallil, Joseph J.] Uniformed Serv Univ Hlth Sci, Bethesda, MD 20814 USA. [Sadoff, Jerald C.] AERAS Global TB Fdn, Rockville, MD 20850 USA. [Goudsmit, Jaap; Pau, Maria Grazia] Crucell Holland BV, Leiden, Netherlands. RP Herzenberg, LA (reprint author), Stanford Univ, Dept Genet, Stanford, CA 94305 USA. EM lenherz@darwin.stanford.edu; lenherz@darwin.stanford.edu; roederer@nih.gov FU National Institute of Allergy and Infectious Diseases [AI058896, AI077395]; National Institute of Allergy and Infectious Diseases, National Institutes of Health FX We thank Judy Stein for assistance with technology transfer, Robert Phelps of PARI Pharma GmbH (Munich, Germany) for providing valuable information and assistance with customization of the device, John-Paul Todd and Alida Ault for assistance with animal protocols and procedures, and the BioQual staff for animal support. This work was supported by National Institute of Allergy and Infectious Diseases Grant AI058896 (to P.A.K.), AI077395 (to L.A.H.), and by the Intramural Research Program of the National Institute of Allergy and Infectious Diseases, National Institutes of Health. NR 24 TC 37 Z9 38 U1 0 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 DEC 21 PY 2010 VL 107 IS 51 BP 22213 EP 22218 DI 10.1073/pnas.1015536108 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 697OB UT WOS:000285521800052 PM 21135247 ER PT J AU Lu, W Isozaki, K Roche, KW Nicoll, RA AF Lu, Wei Isozaki, Kaname Roche, Katherine W. Nicoll, Roger A. TI Synaptic targeting of AMPA receptors is regulated by a CaMKII site in the first intracellular loop of GluA1 SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE GluA2; GluR1; postsynaptic density; hippocampus; pyramidal neurons ID LONG-TERM POTENTIATION; CA1 PYRAMIDAL CELLS; GLUTAMATE-RECEPTOR; PHOSPHORYLATION SITES; HIPPOCAMPAL-NEURONS; LATERAL MOVEMENTS; GLUR1 SUBUNIT; PLASTICITY; TRAFFICKING; SYNAPSES AB The accumulation of AMPA receptors (AMPARs) at synapses is essential for excitatory synaptic transmission. However, the mechanisms underlying synaptic targeting of AMPARs remain elusive. We have now used a molecular replacement approach on an AMPAR-null background to investigate the targeting mechanisms necessary for regulating AMPAR trafficking in the hippocampus. Although there is an extensive literature on the role of the GluA1 C-tail in AMPAR trafficking, there is no effect of overexpressing the C-tail on basal transmission. Instead, we found that the first intracellular loop domain (Loop1) of GluA1, a previously overlooked region within AMPARs, is critical for receptor targeting to synapses, but not for delivery of receptors to the plasma membrane. We also identified a CaMKII phosphorylation site (S567) in the GluA1 Loop1, which is phosphorylated in vitro and in vivo. Furthermore, we show that S567 is a key residue that regulates Loop1-mediated AMPAR trafficking. Thus, our study reveals a unique mechanism for targeting AMPARs to synapses to mediate synaptic transmission. C1 [Lu, Wei; Nicoll, Roger A.] Univ Calif San Francisco, Dept Cellular & Mol Pharmacol, San Francisco, CA 94143 USA. [Isozaki, Kaname; Roche, Katherine W.] Natl Inst Neurol Disorders & Stroke, NIH, Bethesda, MD 20892 USA. [Lu, Wei; Nicoll, Roger A.] Univ Calif San Francisco, Dept Physiol, San Francisco, CA 94143 USA. RP Nicoll, RA (reprint author), Univ Calif San Francisco, Dept Cellular & Mol Pharmacol, San Francisco, CA 94143 USA. EM rochek@ninds.nih.gov; nicoll@cmp.ucsf.edu RI Lu, Wei/E-8110-2011; OI Roche, Katherine/0000-0001-7282-6539 FU American Heart Association; Japan Society for the Promotion of Scienc at the National Institutes of Health; NINDS; National Institute of Mental Health FX We thank K. Bjorgan and M. Cerpas for technical assistance, and all members from the R.A.N. laboratory and K.W.R. laboratory for helpful discussions. We are also grateful for the generosity of Profs. Peter Seeburg and Rolf Sprengel at The Max Planck Institute for Medical Research (Heidelberg, Germany) for sharing individual gene targeted conditional mice for GluA1, GluA2, or GluA3, from which we were able to make the triple floxed Gria1-3fl/fl mice. We also thank the National Institute of Neurological Disorders and Stroke (NINDS) Light Imaging Facility, particularly C. Smith, and the NINDS sequencing facility for DNA sequencing. W.L. is funded by a postdoctoral fellowship from the American Heart Association; K.I. is funded by the Japan Society for the Promotion of Science Research Fellowship for Japanese Biomedical and Behavioral Researchers at the National Institutes of Health; K.W.R. is funded by the NINDS Intramural Research Program; and R.A.N. is funded by grants from the National Institute of Mental Health. NR 41 TC 33 Z9 34 U1 0 U2 9 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 DEC 21 PY 2010 VL 107 IS 51 BP 22266 EP 22271 DI 10.1073/pnas.1016289107 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 697OB UT WOS:000285521800061 PM 21135237 ER PT J AU Thanos, PK Tucci, A Stamos, J Robison, L Wang, GJ Anderson, BJ Volkow, ND AF Thanos, Panayotis K. Tucci, Andrew Stamos, Joshua Robison, Lisa Wang, Gene-Jack Anderson, Brenda J. Volkow, Nora D. TI Chronic forced exercise during adolescence decreases cocaine conditioned place preference in Lewis rats SO BEHAVIOURAL BRAIN RESEARCH LA English DT Article DE Dopamine; Exercise; Cocaine; Conditioned place preference ID DOPAMINE D2 RECEPTOR; DIET-INDUCED OBESITY; SEX-DIFFERENCES; FEMALE RATS; LOCOMOTOR-ACTIVITY; AEROBIC EXERCISE; BIOLOGICAL BASIS; BRAIN DOPAMINE; FIRING RATE; WHEEL AB Chronic physical activity (exercise) may be beneficial in the prevention of substance use disorders; however, the extent to which physical activity can interfere with the reinforcing effects of drugs during the adolescent period, which is one of great vulnerability for drug experimentation, has not been fully evaluated. Here, we assess the effects of chronic forced exercise during adolescence on preference for cocaine using the conditioned place preference (CPP) paradigm in male and female Lewis rats. The group of rats exposed to exercise ran on a treadmill for 6 weeks on a progressive time-increased schedule for up to 1 h of exercise per day, while the groups of sedentary rats remained in their home cage. Following the 6 weeks of exercise exposure, rats were tested for cocaine CPP. Results showed that chronic exercise significantly attenuated cocaine CPP in both males and females compared to a sedentary environment. Furthermore, male exercise rats failed to show significant cocaine CPP. In contrast, female exercise rats still showed cocaine CPP but it was significantly reduced compared to the female sedentary rats. Females also exhibited greater cocaine CPP than males overall. These findings suggest that strategies to promote physical activity during adolescence may be protective against cocaine abuse in both males and females, and these findings merit further investigation. We also corroborate a gender-specific sensitivity to the reinforcing effects of cocaine, highlighting the need to consider gender-tailored exercise interventions for drug abuse prevention. (C) 2010 Published by Elsevier B.V. C1 [Thanos, Panayotis K.; Tucci, Andrew; Stamos, Joshua; Wang, Gene-Jack] Brookhaven Natl Lab, Dept Med, Behav Neuropharmacol & Neuroimaging Lab, Upton, NY 11973 USA. [Thanos, Panayotis K.; Robison, Lisa; Volkow, Nora D.] NIAAA, Lab Neuroimaging, NIH, Bethesda, MD 20892 USA. [Thanos, Panayotis K.; Anderson, Brenda J.] SUNY Stony Brook, Dept Psychol, Stony Brook, NY 11794 USA. RP Thanos, PK (reprint author), Brookhaven Natl Lab, Dept Med, Behav Neuropharmacol & Neuroimaging Lab, Upton, NY 11973 USA. EM thanos@bnl.gov FU NIAAA [AA 11034, AA07574, AA07611]; SULI; IRTA FX This work was supported by the NIAAA (AA 11034 & AA07574, AA07611). We also thank the SULI and IRTA programs for partial support of LSR. We also thank Joe Gatz for technical assistance with the equipment. NR 60 TC 23 Z9 24 U1 0 U2 3 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0166-4328 J9 BEHAV BRAIN RES JI Behav. Brain Res. PD DEC 20 PY 2010 VL 215 IS 1 BP 77 EP 82 DI 10.1016/j.bbr.2010.06.033 PG 6 WC Behavioral Sciences; Neurosciences SC Behavioral Sciences; Neurosciences & Neurology GA 653GG UT WOS:000282076500010 PM 20615434 ER PT J AU Barak, B Williams, A Bielopolski, N Gottfried, I Okun, E Brown, MA Matti, U Rettig, J Stuenkel, EL Ashery, U AF Barak, Boaz Williams, Antionette Bielopolski, Noa Gottfried, Irit Okun, Eitan Brown, Meghan A. Matti, Ulf Rettig, Jens Stuenkel, Edward L. Ashery, Uri TI Tomosyn expression pattern in the mouse hippocampus suggests both presynaptic and postsynaptic functions SO FRONTIERS IN NEUROANATOMY LA English DT Article DE tomosyn isoforms; hippocampus; mossy fiber terminals; CA2 area; synaptic protein AB The protein tomosyn decreases synaptic transmission and release probability of vesicles, and is essential for modulating synaptic transmission in neurons. In this study, we provide a detailed description of the expression and localization patterns of tomosyn1 and tomosyn2 in the subareas of the mouse hippocampus. Using confocal and two-photon high-resolution microscopy we demonstrate that tomosyn colocalizes with several pre- and postsynaptic markers and is found mainly in glutamatergic synapses. Specifically, we show that tomosyn1 is differentially distributed in the mouse hippocampus and concentrated mainly in the hilus and mossy fibers. Surprisingly, we found that tomosyn2 is expressed in the subiculum, CA1 and CA2 pyramidal cell bodies, dendrites and spines, and colocalizes with PSD95, suggesting a postsynaptic role. These results suggest that in addition to the well-characterized presynaptic function of tomosyn in neurotransmitter release, tomosyn2 might have a postsynaptic function, and place tomosyn as a more general regulator of synaptic transmission and plasticity. C1 [Barak, Boaz; Bielopolski, Noa; Gottfried, Irit; Ashery, Uri] Tel Aviv Univ, George S Wise Fac Life Sci, Dept Neurobiol, IL-69978 Tel Aviv, Israel. [Williams, Antionette; Stuenkel, Edward L.] Univ Michigan, Dept Mol & Integrat Physiol, Ann Arbor, MI 48109 USA. [Okun, Eitan; Brown, Meghan A.] NIA, Neurosci Lab, NIH, Baltimore, MD 21224 USA. [Matti, Ulf; Rettig, Jens] Univ Saarland, Inst Physiol, Homburg, Saar, Germany. RP Ashery, U (reprint author), Tel Aviv Univ, George S Wise Fac Life Sci, Dept Neurobiol, Sherman Bldg Room 719, IL-69978 Tel Aviv, Israel. EM uria@post.tau.ac.il RI Rettig, Jens/K-5103-2013; okun, eitan/K-1314-2016; OI Rettig, Jens/0000-0001-6160-3954; okun, eitan/0000-0001-8474-1487; Matti, Ulf/0000-0001-5548-1081 FU Israel Science Foundation [1211/07]; National Institutes of Health [RO1 NS053978] FX We thank Dr. E. F. Indig, Dr. M. Shaharabany and Dr. E. Krause for their technical help. Tomosyn1-knockout mice were kindly provided by Prof. Y. Takai, Kobe University and Prof. J. Miyoshi, Osaka, Japan. This work was supported by grants from the Israel Science Foundation (Grant no. 1211/07; Uri Ashery) and the National Institutes of Health (RO1 NS053978; Edward L. Stuenkel and Uri Ashery). NR 44 TC 9 Z9 9 U1 0 U2 5 PU FRONTIERS RES FOUND PI LAUSANNE PA PO BOX 110, LAUSANNE, 1015, SWITZERLAND SN 1662-5129 J9 FRONT NEUROANAT JI Front. Neuroanat. PD DEC 20 PY 2010 VL 4 AR 149 DI 10.3389/fnana.2010.00149 PG 11 WC Anatomy & Morphology; Neurosciences SC Anatomy & Morphology; Neurosciences & Neurology GA V21HY UT WOS:000208199900001 PM 21191478 ER PT J AU Ishii, M Kikuta, J Shimazu, Y Meier-Schellersheim, M Germain, RN AF Ishii, Masaru Kikuta, Junichi Shimazu, Yutaka Meier-Schellersheim, Martin Germain, Ronald N. TI Chemorepulsion by blood S1P regulates osteoclast precursor mobilization and bone remodeling in vivo SO JOURNAL OF EXPERIMENTAL MEDICINE LA English DT Article ID SPHINGOSINE-1-PHOSPHATE RECEPTORS; SPHINGOSINE 1-PHOSPHATE; CELL-MIGRATION; T-CELLS; CHEMOKINE; EXPRESSION; MARROW AB Sphingosine-1-phosphate (S1P), a lipid mediator enriched in blood, controls the dynamic migration of osteoclast (OC) precursors (OPs) between the blood and bone, in part via the S1P receptor 1 (S1PR1) which directs positive chemotaxis toward S1P. We show that OPs also express S1PR2, an S1P receptor which mediates negative chemotaxis (or chemorepulsion). OP-positive chemotaxis is prominent in gradients with low maximal concentrations of S1P, whereas such behavior is minimal in fields with high maximal S1P concentrations. This reverse-directional behavior is caused by S1PR2-mediated chemorepulsion acting to override S1PR1 upgradient motion. S1PR2-deficient mice exhibit moderate osteopetrosis as a result of a decrease in osteoclastic bone resorption, suggesting that S1PR2 contributes to OP localization on the bones mediated by chemorepulsion away from the blood where S1P levels are high. Inhibition of S1PR2 function by the antagonist JTE013 changed the migratory behavior of monocytoid cells, including OPs, and relieved osteoporosis in a mouse model by limiting OP localization and reducing the number of mature OCs attached to the bone surface. Thus, reciprocal regulation of S1P-dependent chemotaxis controls bone remodeling by finely regulating OP localization. This regulatory axis may be promising as a therapeutic target in diseases affecting OC-dependent bone remodeling. C1 [Ishii, Masaru; Kikuta, Junichi; Shimazu, Yutaka] Osaka Univ, Lab Biol Imaging, WPI Immunol Frontier Res Ctr, Suita, Osaka 5650871, Japan. [Ishii, Masaru; Germain, Ronald N.] NIAID, Lymphocyte Biol Sect, Immunol Lab, NIH, Bethesda, MD 20892 USA. [Meier-Schellersheim, Martin; Germain, Ronald N.] NIAID, Program Syst Immunol & Infect Dis Modeling, NIH, Bethesda, MD 20892 USA. RP Ishii, M (reprint author), Osaka Univ, Lab Biol Imaging, WPI Immunol Frontier Res Ctr, 2-2 Yamadaoka, Suita, Osaka 5650871, Japan. EM mishii@ifrec.osaka-u.ac.jp; rgermain@niaid.nih.gov RI Ishii, Masaru/D-2361-2009; OI Shimazu, Yutaka/0000-0002-1604-7220 FU National Institute of Allergy and Infectious Diseases, NIH; United States Department of Health and Human Services; International Human Frontier Science Program [00387/2006-L, CDA-00059/2009]; Senri Lifescience Foundation; Scientific Research on Innovative Areas [22113007]; Ministry of Education, Science, Sports and Culture of Japan; Ministry of Health, Labor and Welfare of Japan [H21-010]; Takeda Science Foundation; Japan Research Foundation for Clinical Pharmacology; Senri Lifescience Foundation; Mochida Memorial Foundation for Medical and Pharmaceutical Research FX This work was supported in part by the Intramural Research Program of the National Institute of Allergy and Infectious Diseases, NIH, United States Department of Health and Human Services (R.N. Germain), by grants from the International Human Frontier Science Program (LT-00387/2006-L and CDA-00059/2009; to M. Ishii), by a Grants-in-Aid for Encouragement of Young Scientists (A; 22689030), for Scientific Research on Innovative Areas (22113007; to M. Ishii), and a Funding Program for World-Leading Innovative R&D on Science and Technology (FIRST Program) from the Ministry of Education, Science, Sports and Culture of Japan, by Grants-in-Aid for Research on Allergic Disease and Immunology (H21-010; to M. Ishii) from the Ministry of Health, Labor and Welfare of Japan, and by Grants from Takeda Science Foundation (to M. Ishii), from Japan Research Foundation for Clinical Pharmacology (to M. Ishii), from Senri Lifescience Foundation (to M. Ishii), and from Mochida Memorial Foundation for Medical and Pharmaceutical Research (to M. Ishii). NR 21 TC 87 Z9 92 U1 0 U2 7 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 1114 FIRST AVE, 4TH FL, NEW YORK, NY 10021 USA SN 0022-1007 J9 J EXP MED JI J. Exp. Med. PD DEC 20 PY 2010 VL 207 IS 13 BP 2793 EP 2798 DI 10.1084/jem.20101474 PG 6 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA 697HD UT WOS:000285503000003 PM 21135136 ER PT J AU Geldmacher, C Ngwenyama, N Schuetz, A Petrovas, C Reither, K Heeregrave, EJ Casazza, JP Ambrozak, DR Louder, M Ampofo, W Pollakis, G Hill, B Sanga, E Saathoff, E Maboko, L Roederer, M Paxton, WA Hoelscher, M Koup, RA AF Geldmacher, Christof Ngwenyama, Njabulo Schuetz, Alexandra Petrovas, Constantinos Reither, Klaus Heeregrave, Edwin J. Casazza, Joseph P. Ambrozak, David R. Louder, Mark Ampofo, William Pollakis, Georgios Hill, Brenna Sanga, Erica Saathoff, Elmar Maboko, Leonard Roederer, Mario Paxton, William A. Hoelscher, Michael Koup, Richard A. TI Preferential infection and depletion of Mycobacterium tuberculosis-specific CD4 T cells after HIV-1 infection SO JOURNAL OF EXPERIMENTAL MEDICINE LA English DT Article ID AFRICAN GOLD MINERS; IN-VIVO; SIV REPLICATION; FLOW-CYTOMETRY; MBEYA REGION; IFN-GAMMA; IMMUNODEFICIENCY; RESPONSES; DISEASE; MICE AB HIV-1 infection results in the progressive loss of CD4 T cells. In this study, we address how different pathogen-specific CD4 T cells are affected by HIV infection and the cellular parameters involved. We found striking differences in the depletion rates between CD4 T cells to two common opportunistic pathogens, cytomegalovirus (CMV) and Mycobacterium tuberculosis (MTB). CMV-specific CD4 T cells persisted after HIV infection, whereas MTB-specific CD4 T cells were depleted rapidly. CMV-specific CD4 T cells expressed a mature phenotype and produced very little IL-2, but large amounts of MIP-1 beta. In contrast, MTB-specific CD4 T cells were less mature, and most produced IL-2 but not MIP-1 beta. Staphylococcal enterotoxin B-stimulated IL-2-producing cells were more susceptible to HIV infection in vitro than MIP-1 beta-producing cells. Moreover, IL-2 production was associated with expression of CD25, and neutralization of IL-2 completely abrogated productive HIV infection in vitro. HIV DNA was found to be most abundant in IL-2-producing cells, and least abundant in MIP-1 beta-producing MTB-specific CD4 T cells from HIV-infected subjects with active tuberculosis. These data support the hypothesis that differences in function affect the susceptibility of pathogen-specific CD4 T cells to HIV infection and depletion in vivo, providing a potential mechanism to explain the rapid loss of MTB-specific CD4 T cells after HIV infection. C1 [Geldmacher, Christof; Ngwenyama, Njabulo; Petrovas, Constantinos; Casazza, Joseph P.; Ambrozak, David R.; Hill, Brenna; Koup, Richard A.] NIAID, Immunol Lab, NIH, Bethesda, MD 20892 USA. [Roederer, Mario] NIAID, Immunotechnol Sect, NIH, Bethesda, MD 20892 USA. [Louder, Mark] NIAID, Core Virol Sect BSL 3, Vaccine Res Ctr, NIH, Bethesda, MD 20892 USA. [Schuetz, Alexandra; Reither, Klaus; Sanga, Erica; Maboko, Leonard] Referral Hosp, Natl Inst Med Res, Mbeya Med Res Programme, Mbeya, Tanzania. [Heeregrave, Edwin J.; Pollakis, Georgios; Paxton, William A.] Univ Amsterdam, Dept Retrovirol, NL-1105 AZ Amsterdam, Netherlands. [Geldmacher, Christof; Reither, Klaus; Saathoff, Elmar; Hoelscher, Michael] Klinikum Univ Munich, Dept Infect Dis & Trop Med, D-80802 Munich, Germany. [Ampofo, William] Univ Ghana, Noguchi Mem Inst Med Res, Accra, Ghana. RP Geldmacher, C (reprint author), NIAID, Immunol Lab, NIH, Bldg 10, Bethesda, MD 20892 USA. EM geldmacher@lrz.uni-muenchen.de RI Hoelscher, Michael/D-3436-2012; OI Pollakis, Georgios/0000-0002-9659-5461 FU European Commission [ICA_CT-1999-10007, ICA_CT-2002-10048, E.C. DGVIII - AIDCO - SANTE/2006/129-931]; Netherlands Organisation for Scientific Research WOTRO [01.53.2004.025] FX This study has been supported by the European Commission through grants ICA_CT-1999-10007, ICA_CT-2002-10048, and E.C. DGVIII - AIDCO - SANTE/2006/129-931 and a Netherlands Organisation for Scientific Research WOTRO Grant (01.53.2004.025). NR 49 TC 101 Z9 103 U1 0 U2 3 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 1114 FIRST AVE, 4TH FL, NEW YORK, NY 10021 USA SN 0022-1007 J9 J EXP MED JI J. Exp. Med. PD DEC 20 PY 2010 VL 207 IS 13 BP 2869 EP 2881 DI 10.1084/jem.20100090 PG 13 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA 697HD UT WOS:000285503000010 PM 21115690 ER PT J AU Kemble, CK Auxier, J Lynch, SK Bennett, EE Morgan, NY Wen, H AF Kemble, Camille K. Auxier, Julie Lynch, Susanna K. Bennett, Eric E. Morgan, Nicole Y. Wen, Han TI Grazing angle Mach-Zehnder interferometer using reflective phase gratings and a polychromatic, un-collimated light source SO OPTICS EXPRESS LA English DT Article ID RAY; TISSUES AB Normal incidence Talbot-Lau interferometers in x-ray applications have the drawbacks of low fringe visibility with polychromatic sources when the wave propagation distance is increased to achieve higher phase sensitivity, and when fabrication limits the attainable grating density. In contrast, reflective gratings illuminated at grazing angles have dramatically higher effective densities than their physical values. However, new designs are needed for far field interferometers using grazing angle geometry with incoherent light sources. We show that, with the appropriate design and choice of reflective phase gratings, there exist pairs of interfering pathways of exactly equal lengths independent of the incoming beam's incidence angle and wavelength. With a visible light grazing angle Mach-Zehnder interferometer, we show the conditions for achieving near ideal fringe visibility and demonstrate both absolute and differential phase-contrast imaging. We also describe the design parameters of an x-ray interferometer and key factors for its implementation. (C) 2010 Optical Society of America C1 [Kemble, Camille K.; Lynch, Susanna K.; Bennett, Eric E.; Wen, Han] NHLBI, Imaging Phys Sect, NIH, Bethesda, MD 20892 USA. [Auxier, Julie] Natl Inst Biomed Imaging & Bioengn, Intramural Res Programs, NIH, Bethesda, MD 20892 USA. RP Kemble, CK (reprint author), NHLBI, Imaging Phys Sect, NIH, Bldg 10, Bethesda, MD 20892 USA. EM wenh@nhlbi.nih.gov RI Bennett, Eric/A-2551-2013; Wen, Han/G-3081-2010 OI Wen, Han/0000-0001-6844-2997 FU Intramural NIH HHS [ZIA HL004606-14] NR 19 TC 7 Z9 7 U1 0 U2 8 PU OPTICAL SOC AMER PI WASHINGTON PA 2010 MASSACHUSETTS AVE NW, WASHINGTON, DC 20036 USA SN 1094-4087 J9 OPT EXPRESS JI Opt. Express PD DEC 20 PY 2010 VL 18 IS 26 BP 27481 EP 27492 DI 10.1364/OE.18.027481 PG 12 WC Optics SC Optics GA 698HF UT WOS:000285584200114 PM 21197023 ER PT J AU Ma, LA Jensen, JS Mancuso, M Hamasuna, R Jia, QY McGowin, CL Martin, DH AF Ma, Liang Jensen, Jorgen S. Mancuso, Miriam Hamasuna, Ryoichi Jia, Qiuyao McGowin, Chris L. Martin, David H. TI Genetic Variation in the Complete MgPa Operon and Its Repetitive Chromosomal Elements in Clinical Strains of Mycoplasma genitalium SO PLOS ONE LA English DT Article ID POLYMERASE CHAIN-REACTION; FRAGMENT LENGTH POLYMORPHISM; REAL-TIME PCR; NONGONOCOCCAL URETHRITIS; AZITHROMYCIN TREATMENT; PNEUMONIAE; RECOMBINATION; SPECIMENS; SEQUENCES; PROTEIN AB Mycoplasma genitalium has been increasingly recognized as an important microbe not only because of its significant association with human genital tract diseases but also because of its utility as a model for studying the minimum set of genes necessary to sustain life. Despite its small genome, 4.7% of the total genome sequence is devoted to making the MgPa adhesin operon and its nine chromosomal repetitive elements (termed MgPars). The MgPa operon, along with 9 MgPars, is believed to play an important role in pathogenesis of M. genitalium infection and has also served as the main target for development of diagnostic tools. However, genetic variation in the complete MgPa operon and MgPars among clinical strains of M. genitalium has not been addressed. In this study we examined the genetic variation in the complete MgPa operon (approximately 8.5 kb) and full or partial MgPar sequences (0.4-2.6 kb) in 15 geographically diverse strains of M. genitalium. Extensive variation was present in four repeat regions of the MgPa operon (with homology to MgPars) among and within strains while the non-repeat regions (without homology to MgPars) showed low-level variation among strains and no variation within strains. MgPars showed significant variation among strains but were highly homogeneous within strains, supporting gene conversion as the likely recombination mechanism. When applying our sequence data to evaluate published MgPa operon-based diagnostic PCR assays and genotyping systems, we found that 11 of 19 primers contain up to 19 variable nucleotides and that the target for one of two typing systems is located in a hypervariable repeat region, suggesting the likelihood of false results with some of these assays. This study not only provides new insights into the role of the MgPa operon in the pathogenesis of M. genitalium infection but has important implications for the development of diagnostic tools. C1 [Ma, Liang; Mancuso, Miriam; Jia, Qiuyao; McGowin, Chris L.; Martin, David H.] Louisiana State Univ, Infect Dis Sect, Dept Med, Hlth Sci Ctr, New Orleans, LA USA. [Jensen, Jorgen S.] Statens Serum Inst, Mycoplasma Lab, DK-2300 Copenhagen, Denmark. [Hamasuna, Ryoichi] Univ Occupat & Environm Hlth, Dept Urol, Yahatanishi Ku, Kitakyushu, Fukuoka 807, Japan. RP Ma, LA (reprint author), NIH, Dept Crit Care Med, Ctr Clin, Bethesda, MD 20892 USA. EM LMa1@lsuhsc.edu RI Jensen, Jorgen/I-2917-2012; OI Jensen, Jorgen Skov/0000-0002-7464-7435 FU Department of Defense [W81XWH-08-1-0676]; National Institutes of Health [5 U19 AI061972]; Louisiana Vaccine Center; Louisiana State of Regents [149752505J] FX This work was supported by the Department of Defense (grant W81XWH-08-1-0676), the Gulf South Sexually Transmitted Infections/Topical Microbicide Cooperative Research Center grant from the National Institutes of Health (grant 5 U19 AI061972), and the Louisiana Vaccine Center and the South Louisiana Institute for Infectious Disease Research sponsored by the Louisiana State of Regents (grant 149752505J). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 36 TC 15 Z9 17 U1 0 U2 0 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 185 BERRY ST, STE 1300, SAN FRANCISCO, CA 94107 USA SN 1932-6203 J9 PLOS ONE JI PLoS One PD DEC 20 PY 2010 VL 5 IS 12 AR e15660 DI 10.1371/journal.pone.0015660 PG 9 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 698EM UT WOS:000285575200059 PM 21187921 ER PT J AU Ni, T Tu, K Wang, Z Song, S Wu, H Xie, B Scott, KC Grewal, SI Gao, YA Zhu, J AF Ni, Ting Tu, Kang Wang, Zhong Song, Shen Wu, Han Xie, Bin Scott, Kristin C. Grewal, Shiv I. Gao, Yuan Zhu, Jun TI The Prevalence and Regulation of Antisense Transcripts in Schizosaccharomyces pombe SO PLOS ONE LA English DT Article ID BIDIRECTIONAL PROMOTERS; PERVASIVE TRANSCRIPTION; NUCLEOTIDE RESOLUTION; ACTIVE PROMOTERS; HISTONE H2A.Z; YEAST GENOME; RNA-SEQ; GENES; MAPS; IDENTIFICATION AB A strand-specific transcriptome sequencing strategy, directional ligation sequencing or DeLi-seq, was employed to profile antisense transcriptome of Schizosaccharomyces pombe. Under both normal and heat shock conditions, we found that polyadenylated antisense transcripts are broadly expressed while distinct expression patterns were observed for protein-coding and non-coding loci. Dominant antisense expression is enriched in protein-coding genes involved in meiosis or stress response pathways. Detailed analyses further suggest that antisense transcripts are independently regulated with respect to their sense transcripts, and diverse mechanisms might be potentially involved in the biogenesis and degradation of antisense RNAs. Taken together, antisense transcription may have profound impacts on global gene regulation in S. pombe. C1 [Ni, Ting; Tu, Kang; Song, Shen; Wu, Han; Scott, Kristin C.; Zhu, Jun] Duke Univ, Med Ctr, Inst Genome Sci & Policy, Durham, NC 27710 USA. [Ni, Ting; Tu, Kang; Wu, Han; Zhu, Jun] NHLBI, Genet & Dev Biol Ctr, NIH, Bethesda, MD 20892 USA. [Wang, Zhong] DOE Joint Genome Inst, Walnut Creek, CA USA. [Xie, Bin; Gao, Yuan] Johns Hopkins Univ, Div Genom Epigenom & Bioinformat, Lieber Inst Brain Dev, Baltimore, MD USA. [Gao, Yuan] Johns Hopkins Univ, Neuroregenerat & Stem Cell Biol Program, Inst Cell Engn, Baltimore, MD USA. [Grewal, Shiv I.] NCI, Biochem & Mol Biol Lab, NIH, Bethesda, MD 20892 USA. RP Ni, T (reprint author), Duke Univ, Med Ctr, Inst Genome Sci & Policy, Durham, NC 27710 USA. EM jun.zhu@nih.gov RI Wang, Zhong/E-7897-2011; Gao, Yuan/E-1706-2011; Wu, Han/E-3455-2013 OI Wu, Han/0000-0002-3972-698X FU Department of Defense [BC074085P1]; Susan G. Komen for the Cure [KG081324] FX This work was supported by Department of Defense (BC074085P1) and Susan G. Komen for the Cure (KG081324) to J.Z. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 50 TC 33 Z9 34 U1 0 U2 10 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 185 BERRY ST, STE 1300, SAN FRANCISCO, CA 94107 USA SN 1932-6203 J9 PLOS ONE JI PLoS One PD DEC 20 PY 2010 VL 5 IS 12 AR e15271 DI 10.1371/journal.pone.0015271 PG 10 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 698EM UT WOS:000285575200029 PM 21187966 ER PT J AU Chun, KS Lao, HC Langenbach, R AF Chun, Kyung-Soo Lao, Huei-Chen Langenbach, Robert TI The Prostaglandin E-2 Receptor, EP2, Stimulates Keratinocyte Proliferation in Mouse Skin by G Protein-dependent and beta-Arrestin1-dependent Signaling Pathways SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID GROWTH-FACTOR RECEPTOR; BETA-ADRENERGIC-RECEPTOR; SRC FAMILY KINASES; COUPLED RECEPTORS; EGF RECEPTOR; EPITHELIAL CARCINOGENESIS; PROSTANOID RECEPTORS; TUMOR-DEVELOPMENT; KNOCKOUT MICE; ACTIVATION AB The prostaglandin E-2 (PGE2) G protein-coupled receptor (GPCR), EP2, plays important roles in mouse skin tumor development (Chun, K. S., Lao, H. C., Trempus, C. S., Okada, M., and Langenbach, R. (2009) Carcinogenesis 30, 1620-1627). Because keratinocyte proliferation is essential for skin tumor development, EP2-mediated signaling pathways that contribute to keratinocyte proliferation were investigated. A single topical application of the EP2 agonist, butaprost, dose-dependently increased keratinocyte replication via activation of epidermal growth factor receptor (EGFR) and PKA signaling. Because GPCR-mediated activation of EGFR can involve the formation of a GPCR-beta-arrestin-Src signaling complex, the possibility of a beta-arrestin1-Src complex contributing to EP2-mediated signaling in keratinocytes was investigated. Butaprost induced beta-arrestin1-Src complex formation and increased both Src and EGFR activation. A role for beta-arrestin1 in EP2-mediated Src and EGFR activation was demonstrated by the observation that beta-arrestin1 deficiency significantly reduced Src and EGFR activation. In agreement with a beta-arrestin1-Src complex contributing to EGFR activation, Src and EGFR inhibition (PP2 and AG1478, respectively) indicated that Src was upstream of EGFR. Butaprost also induced the activation of Akt, ERK1/2, and STAT3, and both beta-arrestin1 deficiency and EGFR inhibition (AG1478 or gefitinib) decreased their activation. In addition to beta-arrestin1-dependent EGFR activation, butaprost increased PKA activation, as measured by phospho-GSK3 beta (p-GSK3 beta) and p-cAMP-response element-binding protein formation. PKA inhibition (H89 or R-P-adenosine-3',5'-cyclic monophosphorothioate (R-P-cAMPS)) decreased butaprost-induced cAMP-response element-binding protein and ERK activation but did not affect EGFR activation, whereas beta-arrestin1 deficiency decreased EGFR activation but did not affect butaprost-induced PKA activation, thus indicating that they were independent EP2-mediated pathways. Therefore, the results indicate that EP2 contributed to mouse keratinocyte proliferation by G protein-independent, beta-arrestin1- dependent activation of EGFR and G protein-dependent activation of PKA. C1 [Chun, Kyung-Soo; Lao, Huei-Chen; Langenbach, Robert] NIEHS, NIH, Lab Toxicol & Pharmacol, Res Triangle Pk, NC 27709 USA. RP Langenbach, R (reprint author), NIEHS, NIH, Lab Toxicol & Pharmacol, MD C4-09,POB 12233, Res Triangle Pk, NC 27709 USA. EM langenb1@niehs.nih.gov FU NIEHS/National Institutes of Health FX This work was supported, in whole or in part, by the Intramural Research Program of the NIEHS/National Institutes of Health. NR 54 TC 25 Z9 25 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 J9 J BIOL CHEM JI J. Biol. Chem. PD DEC 17 PY 2010 VL 285 IS 51 BP 39672 EP 39681 DI 10.1074/jbc.M110.117689 PG 10 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 692WB UT WOS:000285185500011 PM 20959465 ER PT J AU Trzemecka, A Jacewicz, A Carver, GT Drake, JW Bebenek, A AF Trzemecka, Anna Jacewicz, Agata Carver, Geraldine T. Drake, John W. Bebenek, Anna TI Reversal of a Mutator Activity by a Nearby Fidelity-Neutral Substitution in the RB69 DNA Polymerase Binding Pocket SO JOURNAL OF MOLECULAR BIOLOGY LA English DT Article DE Exo; Pol ID REPLICATION FIDELITY; WILD-TYPE; BIOCHEMICAL BASIS; BASE SELECTIVITY; BACTERIOPHAGE-T4; MUTANT; DISCRIMINATION; PROCESSIVITY; MECHANISMS; MUTATIONS AB Phage RB69 B-family DNA polymerase is responsible for the overall high fidelity of RB69 DNA synthesis Fidelity is compromised when conserved Tyr567, one of the residues that form the nascent polymerase base-pair binding pocket, is replaced by alanine The Y567A mutator mutant has an enlarged binding pocket and can incorporate and extend mispairs efficiently Ser565 is a nearby conserved residue that also contributes to the binding pocket, but a S565G replacement has only a small impact on DNA replication fidelity When Y567A and S565G replacements were combined, mutator activity was strongly decreased compared to that with Y567A replacement alone Analyses conducted both in vivo and in vitro revealed that, compared to Y567A replacement alone, the double mutant mainly reduced base substitution mutations and, to a lesser extent, frameshift mutations The decrease in mutation rates was not due to increased exonuclease activity Based on measurements of DNA binding affinity, mismatch insertion, and mismatch extension, we propose that the recovered fidelity of the double mutant may result, in part, from an increased dissociation of the enzyme from DNA, followed by the binding of the same or another polymerase molecule in either exonuclease mode or polymerase mode An additional antimutagenic factor may be a structural alteration in the polymerase binding pocket described in this article (C) 2010 Elsevier Ltd All rights reserved C1 [Trzemecka, Anna; Jacewicz, Agata; Bebenek, Anna] Polish Acad Sci, Inst Biochem & Biophys, Dept Mol Biol, PL-02104 Warsaw, Poland. [Carver, Geraldine T.; Drake, John W.] NIEHS, Mol Genet Lab, Res Triangle Pk, NC 27709 USA. RP Bebenek, A (reprint author), Polish Acad Sci, Inst Biochem & Biophys, Dept Mol Biol, Pawinskiego 5A, PL-02104 Warsaw, Poland. FU National Institutes of Health, National Institute of Environmental Health Sciences, USA [Z01ES061054]; Polish Ministry of Science and Higher Education [N301014433] FX We thank Bill Beard for providing Fig 9 and both Bill Beard and Mike Murray for critical readings of the manuscript and Bill Konigsberg for advice on the implications of his structural models This research was supported, in part, by funds allocated to project number Z01ES061054 of the Intramural Research Program of the National Institutes of Health, National Institute of Environmental Health Sciences, USA, and by grant N301014433 from the Polish Ministry of Science and Higher Education (to A B) NR 28 TC 7 Z9 8 U1 1 U2 4 PU ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD PI LONDON PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND SN 0022-2836 J9 J MOL BIOL JI J. Mol. Biol. PD DEC 17 PY 2010 VL 404 IS 5 BP 778 EP 793 DI 10.1016/j.jmb.2010.09.058 PG 16 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 699IT UT WOS:000285657800004 PM 20950625 ER PT J AU Jang, H Arce, FT Ramachandran, S Capone, R Lal, R Nussinov, R AF Jang, Hyunbum Arce, Fernando Teran Ramachandran, Srinivasan Capone, Ricardo Lal, Ratnesh Nussinov, Ruth TI beta-Barrel Topology of Alzheimer's beta-Amyloid Ion Channels SO JOURNAL OF MOLECULAR BIOLOGY LA English DT Article DE toxic amyloid ion channels; beta-barrel; U-shaped motif; molecular dynamics; simulations; atomic force microscopy ID SOLID-STATE NMR; LIPID-BILAYERS; 3D STRUCTURE; ZN2+-SENSITIVE CHANNEL; ALANINE DIPEPTIDE; CALCIUM-CHANNELS; PEPTIDE CHANNELS; OUTER-MEMBRANE; PRION PROTEIN; SHEET BARRELS AB Emerging evidence supports the ion channel mechanism for Alzheimer's disease pathophysiology wherein small beta-amyloid (A beta) oligomers insert into the cell membrane, forming toxic ion channels and destabilizing the cellular ionic homeostasis Solid-state NMR-based data of amyloid oligomers in solution indicate that they consist of a double-layered beta-sheets where each monomer folds into beta-strand-turn-beta-strand and the monomers are stacked atop each other In the membrane, A beta peptides are proposed to be beta-type structures Experimental structural data available from atomic force microscopy (AFM) imaging of A beta oligomers in membranes reveal heterogeneous channel morphologies Previously, we modeled the channels in a non-tilted organization, parallel with the cross-membrane normal Here, we modeled a beta-barrel-like organization beta-Barrels are common in transmembrane toxin pores, typically consisting of a monomeric chain forming a pore, organized in a single-layered beta-sheet with antiparallel beta-strands and a right-handed twist Our explicit solvent molecular dynamics simulations of a range of channel sizes and polymorphic turns and comparisons of these with AFM image dimensions support a beta-barrel channel organization Different from the transmembrane beta-barrels where the monomers are folded into a circular beta-sheet with antiparallel beta-strands stabihzed by the connecting loops, these A beta barrels consist of multimeric chains forming double beta-sheets with parallel beta-strands, where the strands of each monomer are connected by a turn Although the A beta barrels adopt the right-handed beta-sheet twist, the barrels still break into heterogeneous, loosely attached subunits, in good agreement with AFM images and previous modeling The subunits appear mobile, allowing unregulated, hence toxic, ion flux (C) 2010 Elsevier Ltd All rights reserved C1 [Jang, Hyunbum; Nussinov, Ruth] Natl Canc Inst Frederick, Ctr Canc Res Nanobiol Program, SAIC Frederick Inc, Frederick, MD 21702 USA. [Arce, Fernando Teran; Ramachandran, Srinivasan; Capone, Ricardo; Lal, Ratnesh] Univ Calif San Diego, Dept Bioengn, La Jolla, CA 92093 USA. [Arce, Fernando Teran; Ramachandran, Srinivasan; Capone, Ricardo; Lal, Ratnesh] Univ Calif San Diego, Dept Mech & Aerosp Engn, La Jolla, CA 92093 USA. [Nussinov, Ruth] Tel Aviv Univ, Sackler Sch Med, Dept Human Mol Genet, IL-69978 Tel Aviv, Israel. [Nussinov, Ruth] Tel Aviv Univ, Sackler Sch Med, Dept Biochem, IL-69978 Tel Aviv, Israel. RP Nussinov, R (reprint author), Natl Canc Inst Frederick, Ctr Canc Res Nanobiol Program, SAIC Frederick Inc, Frederick, MD 21702 USA. RI Capone, Ricardo/D-1943-2010 OI Capone, Ricardo/0000-0002-7327-9837 FU National Cancer Institute, National Institutes of Health (NIH) [HHSN261200800001E]; National Cancer Institute Center for Cancer Research, NIH; National Institute on Aging, NIH FX This project has been funded m whole or m 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 U S Government This research was supported in part by the Intramural Research Program of the National Cancer Institute Center for Cancer Research, NIH This research was also supported by the National Institute on Aging, NIH, extramural program (R L) All simulations had been performed using the high-performance computational facilities of the Biowulf PC/Linux cluster at the NIH NR 92 TC 54 Z9 55 U1 4 U2 31 PU ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD PI LONDON PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND SN 0022-2836 J9 J MOL BIOL JI J. Mol. Biol. PD DEC 17 PY 2010 VL 404 IS 5 BP 917 EP 934 DI 10.1016/j.jmb.2010.10.025 PG 18 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 699IT UT WOS:000285657800014 PM 20970427 ER PT J AU Mitchell, K Bates, BD Keller, JM Lopez, M Scholl, L Navarro, J Madian, N Haspel, G Nemenov, MI Iadarola, MJ AF Mitchell, Kendall Bates, Brian D. Keller, Jason M. Lopez, Matthew Scholl, Lindsey Navarro, Julia Madian, Nicholas Haspel, Gal Nemenov, Michael I. Iadarola, Michael J. TI Ablation of rat TRPV1-expressing Adelta/C-fibers with resiniferatoxin: analysis of withdrawal behaviors, recovery of function and molecular correlates SO MOLECULAR PAIN LA English DT Article ID PRIMARY SOMATOSENSORY CORTEX; VANILLOID RECEPTOR TRPV1; DORSAL-ROOT GANGLION; INFRARED DIODE-LASER; SENSORY NEURONS; SPINAL-CORD; GENE-EXPRESSION; CONDUCTION-VELOCITY; CAPSAICIN RECEPTOR; PRIMARY AFFERENT AB Background: Ablation of TRPV1-expressing nociceptive fibers with the potent capsaicin analog resiniferatoxin (RTX) results in long lasting pain relief. RTX is particularly adaptable to focal application, and the induced chemical axonopathy leads to analgesia with a duration that is influenced by dose, route of administration, and the rate of fiber regeneration. TRPV1 is expressed in a subpopulation of unmyelinated C-and lightly myelinated Adelta fibers that detect changes in skin temperature at low and high rates of noxious heating, respectively. Here we investigate fiber-type specific behaviors, their time course of recovery and molecular correlates of axon damage and nociception using infrared laser stimuli following an RTX-induced peripheral axonopathy. Results: RTX was injected into rat hind paws (mid-plantar) to produce thermal hypoalgesia. An infrared diode laser was used to stimulate Adelta fibers in the paw with a small-diameter (1.6 mm), high-energy, 100 msec pulse, or C-fibers with a wide-diameter (5 mm), long-duration, low-energy pulse. We monitored behavioral responses to indicate loss and regeneration of fibers. At the site of injection, responses to C-fiber stimuli were significantly attenuated for two weeks after 5 or 50 ng RTX. Responses to Adelta stimuli were significantly attenuated for two weeks at the highest intensity stimulus, and for 5 weeks to a less intense Adelta stimulus. Stimulation on the toe, a site distal to the injection, showed significant attenuation of Adelta responses for 7-8 weeks after 5 ng, or 9-10 weeks after 50 ng RTX. In contrast, responses to C-fiber stimuli exhibited basically normal responses at 5 weeks after RTX. During the period of fiber loss and recovery, molecular markers for nerve regeneration (ATF3 and galanin) are upregulated in the dorsal root ganglia (DRG) when behavior is maximally attenuated, but markers of nociceptive activity (c-Fos in spinal cord and MCP-1 in DRG), although induced immediately after RTX treatment, returned to normal. Conclusion: Behavioral recovery following peripheral RTX treatment is linked to regeneration of TRPV1-expressing Adelta and C-fibers and sustained expression of molecular markers. Infrared laser stimulation is a potentially valuable tool for evaluating the behavioral role of Adelta fibers in pain and pain control. C1 [Mitchell, Kendall; Bates, Brian D.; Keller, Jason M.; Lopez, Matthew; Scholl, Lindsey; Navarro, Julia; Madian, Nicholas; Iadarola, Michael J.] Natl Inst Dent & Craniofacial Res, Neurobiol & Pain Therapeut Sect, Lab Sensory Biol, NIH, Bethesda, MD USA. [Nemenov, Michael I.] Stanford Univ, Dept Anesthesia, Palo Alto, CA 94304 USA. [Nemenov, Michael I.] Lasmed LLC, Mountain View, CA USA. [Haspel, Gal] NINDS, Neural Control Lab, Sect Dev Neurobiol, NIH, Bethesda, MD 20892 USA. RP Iadarola, MJ (reprint author), Natl Inst Dent & Craniofacial Res, Neurobiol & Pain Therapeut Sect, Lab Sensory Biol, NIH, Bethesda, MD USA. EM miadarola@dir.nidcr.nih.gov RI Nemenov, Mike/I-7477-2012; OI Haspel, Gal/0000-0001-6701-697X FU NIDCR, NIH, DHHS; NIH [DE015731, NS046951] FX This research was supported by the Intramural Research Program, NIDCR, NIH, DHHS. NIH grants DE015731 and NS046951 are gratefully acknowledged. We thanks Dr Daphne Soares for the loan of high speed camera system. NR 57 TC 27 Z9 28 U1 0 U2 5 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1744-8069 J9 MOL PAIN JI Mol. Pain PD DEC 17 PY 2010 VL 6 AR 94 DI 10.1186/1744-8069-6-94 PG 13 WC Neurosciences SC Neurosciences & Neurology GA 705GE UT WOS:000286116100001 PM 21167052 ER PT J AU Chadwick, W Zhou, Y Park, SS Wang, LY Mitchell, N Stone, MD Becker, KG Martin, B Maudsley, S AF Chadwick, Wayne Zhou, Yu Park, Sung-Soo Wang, Liyun Mitchell, Nicholas Stone, Matthew D. Becker, Kevin G. Martin, Bronwen Maudsley, Stuart TI Minimal Peroxide Exposure of Neuronal Cells Induces Multifaceted Adaptive Responses SO PLOS ONE LA English DT Article ID HYPOXIA-INDUCIBLE FACTOR-1-ALPHA; CHROMATIN PROTEIN HMGB2; GROWTH-FACTOR RECEPTOR; ALZHEIMERS-DISEASE; OXIDATIVE STRESS; PREMATURE SENESCENCE; NEUROTROPHIC FACTOR; LIFE-SPAN; PARKINSONS-DISEASE; MESSENGER-RNA AB Oxidative exposure of cells occurs naturally and may be associated with cellular damage and dysfunction. Protracted low level oxidative exposure can induce accumulated cell disruption, affecting multiple cellular functions. Accumulated oxidative exposure has also been proposed as one of the potential hallmarks of the physiological/pathophysiological aging process. We investigated the multifactorial effects of long-term minimal peroxide exposure upon SH-SY5Y neural cells to understand how they respond to the continued presence of oxidative stressors. We show that minimal protracted oxidative stresses induce complex molecular and physiological alterations in cell functionality. Upon chronic exposure to minimal doses of hydrogen peroxide, SH-SY5Y cells displayed a multifactorial response to the stressor. To fully appreciate the peroxide-mediated cellular effects, we assessed these adaptive effects at the genomic, proteomic and cellular signal processing level. Combined analyses of these multiple levels of investigation revealed a complex cellular adaptive response to the protracted peroxide exposure. This adaptive response involved changes in cytoskeletal structure, energy metabolic shifts towards glycolysis and selective alterations in transmembrane receptor activity. Our analyses of the global responses to chronic stressor exposure, at multiple biological levels, revealed a viable neural phenotype in-part reminiscent of aged or damaged neural tissue. Our paradigm indicates how cellular physiology can subtly change in different contexts and potentially aid the appreciation of stress response adaptations. C1 [Chadwick, Wayne; Zhou, Yu; Park, Sung-Soo; Wang, Liyun; Stone, Matthew D.; Maudsley, Stuart] NIA, Receptor Pharmacol Unit, NIH, Baltimore, MD 21224 USA. [Mitchell, Nicholas] St Bonaventure Univ, Dept Biol, St Bonaventure, NY 14778 USA. [Becker, Kevin G.] NIA, Gene Express & Genom Unit, Res Resources Branch, NIH, Baltimore, MD 21224 USA. [Martin, Bronwen] NIA, Metab Unit, NIH, Baltimore, MD 21224 USA. RP Chadwick, W (reprint author), NIA, Receptor Pharmacol Unit, NIH, Baltimore, MD 21224 USA. EM maudsleyst@mail.nih.gov RI Zhou, Yu/M-7975-2014; OI Becker, Kevin/0000-0002-6794-6656 FU National Institute on Aging FX This research was supported by the Intramural Research Program of the National Institute on Aging. The funding authority had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 156 TC 24 Z9 24 U1 0 U2 3 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 185 BERRY ST, STE 1300, SAN FRANCISCO, CA 94107 USA SN 1932-6203 J9 PLOS ONE JI PLoS One PD DEC 17 PY 2010 VL 5 IS 12 AR e14352 DI 10.1371/journal.pone.0014352 PG 26 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 698DS UT WOS:000285572900002 PM 21179406 ER PT J AU Sebbane, F Jarrett, C Gardner, D Long, D Hinnebusch, BJ AF Sebbane, Florent Jarrett, Clayton Gardner, Donald Long, Daniel Hinnebusch, B. Joseph TI Role of the Yersinia pestis Yersiniabactin Iron Acquisition System in the Incidence of Flea-Borne Plague SO PLOS ONE LA English DT Article ID PASTEURELLA PESTIS; PIGMENTATION; TRANSMISSION; DELETION AB Plague is a flea-borne zoonosis caused by the bacterium Yersinia pestis. Y. pestis mutants lacking the yersiniabactin (Ybt) siderophore-based iron transport system are avirulent when inoculated intradermally but fully virulent when inoculated intravenously in mice. Presumably, Ybt is required to provide sufficient iron at the peripheral injection site, suggesting that Ybt would be an essential virulence factor for flea-borne plague. Here, using a flea-to-mouse transmission model, we show that a Y. pestis strain lacking the Ybt system causes fatal plague at low incidence when transmitted by fleas. Bacteriology and histology analyses revealed that a Ybt-negative strain caused only primary septicemic plague and atypical bubonic plague instead of the typical bubonic form of disease. The results provide new evidence that primary septicemic plague is a distinct clinical entity and suggest that unusual forms of plague may be caused by atypical Y. pestis strains. C1 [Sebbane, Florent] Inst Pasteur, Ctr Infect & Immun Lille, Equipe Peste & Yersinia Pestis, F-59019 Lille, France. [Sebbane, Florent] INSERM, U1019, F-59045 Lille, France. [Sebbane, Florent] Inst Pasteur, Ctr Immunol & Biol Parasitaire, CNRS, UMR8204, F-59019 Lille, France. [Sebbane, Florent] Univ Lille Nord France, Lille, France. [Sebbane, Florent] Ctr Infect & Immun Lille, UDSL, Lille, France. [Jarrett, Clayton; Hinnebusch, B. Joseph] NIAID, Lab Zoonot Pathogens, Rocky Mt Labs, NIH, Hamilton, MT USA. [Jarrett, Clayton; Gardner, Donald; Long, Daniel; Hinnebusch, B. Joseph] NIAID, Vet Pathol Sect, Rocky Mt Labs, NIH, Hamilton, MT USA. RP Sebbane, F (reprint author), Inst Pasteur, Ctr Infect & Immun Lille, Equipe Peste & Yersinia Pestis, F-59019 Lille, France. EM florent.sebbane@inserm.fr FU Division of Intramural Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health; Institut National de la Sante et de la Recherche Medicale FX This work was supported by the Division of Intramural Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health; and Institut National de la Sante et de la Recherche Medicale. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 19 TC 14 Z9 15 U1 0 U2 6 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 185 BERRY ST, STE 1300, SAN FRANCISCO, CA 94107 USA SN 1932-6203 J9 PLOS ONE JI PLoS One PD DEC 17 PY 2010 VL 5 IS 12 AR e14379 DI 10.1371/journal.pone.0014379 PG 4 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 698DS UT WOS:000285572900011 PM 21179420 ER PT J AU Waxman, AJ Mink, PJ Devesa, SS Anderson, WF Weiss, BM Kristinsson, SY McGlynn, KA Landgren, O AF Waxman, Adam J. Mink, Pamela J. Devesa, Susan S. Anderson, William F. Weiss, Brendan M. Kristinsson, Sigurdur Y. McGlynn, Katherine A. Landgren, Ola TI Racial disparities in incidence and outcome in multiple myeloma: a population-based study SO BLOOD LA English DT Article ID UNDETERMINED SIGNIFICANCE MGUS; STEM-CELL TRANSPLANTATION; MONOCLONAL GAMMOPATHY; SOCIOECONOMIC-STATUS; PLUS DEXAMETHASONE; AFRICAN-AMERICAN; UNITED-STATES; SURVIVAL; RACE; CANCER AB Multiple myeloma (MM) is the most common hematologic malignancy in blacks. Some prior studies suggest inferior survival in blacks; others suggest similar survival. Using the original 9 Surveillance, Epidemiology, and End Results registries, we conducted a large-scale population-based study including 5798 black and 28 939 white MM patients diagnosed 1973-2005, followed through 2006. Age-adjusted incidence rates, disease-specific survival, and relative survival rates were calculated by race, age, and time period of diagnosis. Mean age at diagnosis was 65.8 and 69.8 years for blacks and whites, respectively (P < .001). Incidence among blacks was m twice that among whites; this disparity was greater among patients < 50 years (P = .002). Over the entire study period, disease-specific and relative survival rates were higher in blacks than whites (P < .001). For whites, 5-year relative survival rates increased significantly 1973-1993 to 1994-1998 (26.3% to 30.8%; P < .001) and 1994-1998 to 1999-2005 (30.8% to 35.0%; P = .004). Survival improvements among blacks were smaller and nonsignificant (1973-1993 to 1999-2005: 31.0% to 34.1%; P = .07). We found (1) a younger age of onset among blacks; (2) better survival in blacks 1973-2005; and (3) significant survival improvement among whites over time, with smaller, nonsignificant change seen among blacks, possibly due to unequal access to and/or disparate responsiveness to novel therapies. (Blood. 2010; 116(25): 5501-5506) C1 [Landgren, Ola] NCI, NIH, Ctr Canc Res, Med Oncol Branch, Bethesda, MD 20892 USA. [Mink, Pamela J.] Emory Univ, Rollins Sch Publ Hlth, Dept Epidemiol, Atlanta, GA 30322 USA. [Devesa, Susan S.; Anderson, William F.; McGlynn, Katherine A.] NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. [Weiss, Brendan M.] Walter Reed Army Med Ctr, Washington, DC 20307 USA. [Kristinsson, Sigurdur Y.] Karolinska Univ Hosp & Inst, Stockholm, Sweden. RP Landgren, O (reprint author), NCI, NIH, Ctr Canc Res, Med Oncol Branch, 9000 Rockville Pike,Bldg 10,Rm 13N240, Bethesda, MD 20892 USA. EM landgreo@mail.nih.gov RI Kristinsson, Sigurdur /M-2910-2015 OI Kristinsson, Sigurdur /0000-0002-4964-7476 FU NCI of the National Institutes of Health (NIH); NIH; Foundation for NIH; Pfizer Inc FX This work was supported by the Intramural Research Program of the NCI of the National Institutes of Health (NIH).; The authors declare no competing financial interests. A.J.W. is a member of the NIH Clinical Research Training Program, which is funded jointly by the NIH and the Foundation for NIH (in part by a grant from Pfizer Inc). NR 48 TC 88 Z9 89 U1 0 U2 3 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD DEC 16 PY 2010 VL 116 IS 25 BP 5501 EP 5506 DI 10.1182/blood-2010-07-298760 PG 6 WC Hematology SC Hematology GA 695PE UT WOS:000285383900013 PM 20823456 ER PT J AU Moir, S Buckner, CM Ho, J Wang, W Chen, J Waldner, AJ Posada, JG Kardava, L O'Shea, MA Kottilil, S Chun, TW Proschan, MA Fauci, AS AF Moir, Susan Buckner, Clarisa M. Ho, Jason Wang, Wei Chen, Jenny Waldner, Amy J. Posada, Jacqueline G. Kardava, Lela O'Shea, Marie A. Kottilil, Shyam Chun, Tae-Wook Proschan, Michael A. Fauci, Anthony S. TI B cells in early and chronic HIV infection: evidence for preservation of immune function associated with early initiation of antiretroviral therapy SO BLOOD LA English DT Article ID INFLUENZA VACCINATION; ANTIBODY-RESPONSE; MEMORY; INDIVIDUALS; DISEASE; IMMUNIZATION; VIRUS; HAART; HYPERGAMMAGLOBULINEMIA; SUBPOPULATIONS AB Characterization of lymphocytes including B cells during early versus chronic HIV infection is important for understanding the impact of chronic viremia on immune cell function. In this setting, we investigated B cells before and after reduction of HIV plasma viremia by antiretroviral therapy (ART). At baseline, peripheral blood B-cell counts were significantly lower in both early and chronic HIV-infected individuals compared with uninfected controls. Similar to CD4(+) but not CD8(+) T cells, B-cell numbers in both groups increased significantly after ART. At baseline, B cells of early HIV-infected individuals were composed of a higher percentage of plasmablasts and resting memory B cells compared with chronic HIV-infected individuals whose B cells were composed of a higher percentage of immature/transitional and exhausted B cells compared with their early infection counterparts. At 1 year after ART, the percentage of resting memory B cells remained higher in early compared with chronic HIV-infected individuals. This difference translated into a better functional profile in that memory B-cell responses to HIV and non-HIV antigens were superior in early-compared with chronic-treated HIV infected individuals. These findings provide new insights on B cells in HIV infection and how early initiation of ART may prevent irreversible immune system damage. (Blood. 2010; 116(25): 5571-5579) C1 [Moir, Susan; Buckner, Clarisa M.; Ho, Jason; Wang, Wei; Chen, Jenny; Waldner, Amy J.; Posada, Jacqueline G.; Kardava, Lela; O'Shea, Marie A.; Kottilil, Shyam; Chun, Tae-Wook; Fauci, Anthony S.] NIAID, Immunoregulat Lab, NIH, Bethesda, MD 20892 USA. [Chen, Jenny] Howard Hughes Med Inst, NIH Res Scholar Program, Chevy Chase, MD USA. [Proschan, Michael A.] NIAID, Biostat Res Branch, NIH, Bethesda, MD 20892 USA. RP Moir, S (reprint author), NIAID, Immunoregulat Lab, NIH, 9000 Rockville Pike,Bldg 10,Rm 6A02, Bethesda, MD 20892 USA. EM smoir@niaid.nih.gov FU NIAID, NIH FX This work was supported by the Intramural Research Program of NIAID, NIH. NR 49 TC 102 Z9 107 U1 1 U2 12 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD DEC 16 PY 2010 VL 116 IS 25 BP 5571 EP 5579 DI 10.1182/blood-2010-05-285528 PG 9 WC Hematology SC Hematology GA 695PE UT WOS:000285383900020 PM 20837780 ER PT J AU Guech-Ongey, M Simard, EP Anderson, WF Engels, EA Bhatia, K Devesa, SS Mbulaiteye, SM AF Guech-Ongey, Mercy Simard, Edgar P. Anderson, William F. Engels, Eric A. Bhatia, Kishor Devesa, Susan S. Mbulaiteye, Sam M. TI AIDS-related Burkitt lymphoma in the United States: what do age and CD4 lymphocyte patterns tell us about etiology and/or biology? SO BLOOD LA English DT Article ID HUMAN-IMMUNODEFICIENCY-VIRUS; INDUCED CYTIDINE DEAMINASE; DISEASE; CANCER; IMMUNOSUPPRESSION; EXPRESSION; INFECTION; DIAGNOSIS; FEATURES; LINKAGE AB Trimodal or bimodal age-specific incidence rates for Burkitt lymphoma (BL) were observed in the United States general population, but the role of immunosuppression could not be excluded. Incidence rates, rate ratios, and 95% confidence intervals for BL and other non-Hodgkin lymphoma (NHL), by age and CD4 lymphocyte count categories, were estimated using Poisson regression models using data from the United States HIV/AIDS Cancer Match study (1980-2005). BL incidence was 22 cases per 100 000 person-years and 586 for non-BL NHL. Adjusted BL incidence rate ratio among males was 1.6x that among females and among non-Hispanic blacks, 0.4x that among non-Hispanic whites, but unrelated to HIV-transmission category. Non-BL NHL incidence increased from childhood to adulthood; in contrast, 2 age-specific incidence peaks during the pediatric and adult/geriatric years were observed for BL. Non-BL NHL incidence rose steadily with decreasing CD4 lymphocyte counts; in contrast, BL incidence was lowest among people with <= 50 CD4 lymphocytes/mu L versus those with >= 250 CD4 lymphocytes/mu L (incidence rate ratio 0.3 [95% confidence interval = 0.2-0.6]). The bimodal peaks for BL, in contrast to non-BL NHL, suggest effects of noncumulative risk factors at different ages. Under-ascertainment or biological reasons may account for BL deficit at low CD4 lymphocyte counts. (Blood. 2010; 116(25): 5600-5604) C1 [Guech-Ongey, Mercy; Simard, Edgar P.; Engels, Eric A.; Bhatia, Kishor; Mbulaiteye, Sam M.] NCI, Infect & Immunoepidemiol Branch, Div Canc Epidemiol & Genet, NIH,Dept Hlth & Human Serv, Bethesda, MD 20892 USA. [Anderson, William F.; Devesa, Susan S.] NCI, Biostat Branch, Div Canc Epidemiol & Genet, NIH,Dept Hlth & Human Serv, Bethesda, MD 20892 USA. RP Guech-Ongey, M (reprint author), NCI, Infect & Immunoepidemiol Branch, Div Canc Epidemiol & Genet, NIH,Dept Hlth & Human Serv, 6120 Execut Blvd,Execut Plaza S,Rm 7078, Rockville, MD 20852 USA. EM guechome@mail.nih.gov FU National Cancer Institute, National Institutes of Health, Department of Health and Human Services [N02-CP-31003, N01-CO-12400] FX This work was supported by the Intramural Research Program of the National Cancer Institute (contracts N02-CP-31003 and N01-CO-12400), National Institutes of Health, Department of Health and Human Services. NR 40 TC 40 Z9 44 U1 0 U2 1 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD DEC 16 PY 2010 VL 116 IS 25 BP 5600 EP 5604 DI 10.1182/blood-2010-03-275917 PG 5 WC Hematology SC Hematology GA 695PE UT WOS:000285383900023 PM 20813897 ER PT J AU Li, J Maruyama, T Zhang, P Konkel, JE Hoffman, V Zamarron, B Chen, WJ AF Li, Jun Maruyama, Takashi Zhang, Pin Konkel, Joanne E. Hoffman, Victoria Zamarron, Brian Chen, WanJun TI Mutation of inhibitory helix-loop-helix protein Id3 causes gamma delta T-cell lymphoma in mice SO BLOOD LA English DT Article ID TRANSCRIPTION FACTOR FOXP3; OF-THE-LITERATURE; SJOGRENS-SYNDROME; KNOCKOUT MICE; ACTIVATION; LINEAGE; GROWTH AB Human gamma delta T-cell lymphoma is a rare clinicopathologic entity with aggressive course and poor prognosis. The etiology and pathogenesis of gamma delta T-cell lymphoma is unknown. We show here that mice with deficiency in inhibitory helix-loop-helix protein Id3 (Id3(-/-)) developed gamma delta T-cell lymphoma that resembled human gamma delta T-cell lymphoma. The Id3(-/-) mice with lymphoma showed splenomegaly, hepatomegaly, and lymphadenopathy with involvement of bone marrow, thymus, kidney, and lungs between 6 and 15 months of age. Phenotypic analysis revealed that lymphomatous cells were cluster of differentiation (CD)3(+), gamma delta T-cell receptor (TCR)(+), and gamma delta TCR(-), and expressed CD8(+)CD4(-), CD4(+)CD8(-), or a mixture of the two. Id3(-/-) gamma delta T-cell lymphoma used predominantly V gamma 1.1, some V gamma 3, yet no V gamma 2 TCR, and some showed increased levels of the oncogene c-Myc. Strikingly, adoptive transfer of the gamma delta T-cell lymphoma into syngeneic Rag1(-/-) mice resulted in aggressive gamma delta T-cell lymphoma, identical to the Id3(-/-) donor. Thus, our data demonstrate that Id3 regulates the development of gamma delta T-cell lymphoma in mice, raising a possibility of Id3 gene mutation in human gamma delta T-cell lymphoma. Our model will provide a tool for studying the molecular mechanisms and development of human gamma delta T-cell lymphoma. (Blood. 2010; 116(25): 5615-5621) C1 [Li, Jun; Maruyama, Takashi; Zhang, Pin; Konkel, Joanne E.; Zamarron, Brian; Chen, WanJun] NIDCR, MIU, Oral Infect & Immun Branch, Bethesda, MD 20892 USA. [Hoffman, Victoria] NIH, Diagnost & Res Serv Branch, Div Vet Resources, Bethesda, MD 20892 USA. RP Chen, WJ (reprint author), NIDCR, MIU, Oral Infect & Immun Branch, Bldg 30,Rm 304,30 Convent Dr, Bethesda, MD 20892 USA. EM wchen@mail.nih.gov RI Li, Jun/N-6267-2015 FU National Institutes of Health, National Institute of Dental and Craniofacial Research FX This research was supported by the Intramural Research Program of the National Institutes of Health, National Institute of Dental and Craniofacial Research. NR 30 TC 16 Z9 16 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD DEC 16 PY 2010 VL 116 IS 25 BP 5615 EP 5621 DI 10.1182/blood-2010-03-274506 PG 7 WC Hematology SC Hematology GA 695PE UT WOS:000285383900025 PM 20852128 ER PT J AU Szabova, L Son, MY Shi, J Sramko, M Yamada, SS Swaim, WD Zerfas, P Kahan, S Holmbeck, K AF Szabova, Ludmila Son, Mee-Young Shi, Joanne Sramko, Marek Yamada, Susan S. Swaim, William D. Zerfas, Patricia Kahan, Stacie Holmbeck, Kenn TI Membrane-type MMPs are indispensable for placental labyrinth formation and development SO BLOOD LA English DT Article ID MATRIX METALLOPROTEINASES; EXTRACELLULAR-MATRIX; CATHEPSIN PROTEASES; MOUSE PLACENTA; MT1-MMP; EXPRESSION; IMPLANTATION; DISEASE; DECIDUALIZATION; ANGIOGENESIS AB The membrane-type matrix metalloproteinases (MT-MMPs) are essential for pericellular matrix remodeling in late stages of development, as well as in growth and tissue homeostasis in postnatal life. Although early morphogenesis is perceived to involve substantial tissue remodeling, the roles of MT-MMPs in these processes are only partially characterized. Here we explore the functions of 2 prominently expressed MT-MMPs, MT1-MMP and MT2-MMP, and describe their roles in the process of placental morphogenesis. The fetal portion of the placenta, in particular the labyrinth (LA), displays strong overlapping expression of MT1-MMP and MT2-MMP, which is critical for syncytiotrophoblast formation and in turn for fetal vessels. Disruption of trophoblast syncytium formation consequently leads to developmental arrest with only a few poorly branched fetal vessels entering the LA causing embryonic death at embryonic day 11.5. Through knockdown of MMP expression, we demonstrate that either MT1-MMP or MT2-MMP is crucial specifically during development of the LA. In contrast, knockdown of MT-MMP activity after LA formation is compatible with development to term and postnatal life. Taken together these data identify essential but interchangeable roles for MT1-MMP or MT2-MMP in placental vasculogenesis and provide the first example of selective temporal and spatial MMP activity required for development of the mouse embryo. (Blood. 2010;116(25):5752-5761) C1 [Szabova, Ludmila; Son, Mee-Young; Shi, Joanne; Sramko, Marek; Yamada, Susan S.; Kahan, Stacie; Holmbeck, Kenn] Natl Inst Dent & Craniofacial Res, Matrix Metalloproteinase Unit, Craniofacial & Skeletal Dis Branch, NIH, Bethesda, MD 20892 USA. [Swaim, William D.] Natl Inst Dent & Craniofacial Res, Mol Physiol & Therapeut Branch, NIH, Bethesda, MD 20892 USA. [Zerfas, Patricia] NIH, Div Vet Resources, Off Res Serv, Bethesda, MD 20892 USA. RP Holmbeck, K (reprint author), Natl Inst Dent & Craniofacial Res, Matrix Metalloproteinase Unit, Craniofacial & Skeletal Dis Branch, NIH, Bldg 30,Rm 125,30 Convent Dr,MSC 4380, Bethesda, MD 20892 USA. EM kenn.holmbeck@nih.gov FU Division of Intramural Research, National Institutes of Health; Korea Science and Engineering Foundation FX This study was supported by the Division of Intramural Research, NIDCR of the Intramural Research Program, National Institutes of Health. M.S. was supported in part by postdoctoral fellowship funds from the Korea Science and Engineering Foundation. NR 33 TC 16 Z9 16 U1 0 U2 1 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD DEC 16 PY 2010 VL 116 IS 25 BP 5752 EP 5761 DI 10.1182/blood2009-10-249847 PG 10 WC Hematology SC Hematology GA 695PE UT WOS:000285383900041 PM 20858856 ER PT J AU Feng, CG Sher, A AF Feng, Carl G. Sher, Alan TI Parasites Paralyze Cellular Host Defense System to Promote Virulence SO CELL HOST & MICROBE LA English DT Editorial Material ID TOXOPLASMA-GONDII; PARASITOPHOROUS VACUOLE; GTPASES AB To promote their survival, intracellular pathogens must confront microbicidal activities induced by interferons. In this issue of Cell Host & Microbe, Fentress et al. show that Toxoplasma gondii evades intracellular killing by deploying a virulence determinant, ROP18, which acts by directly phosphorylating and disabling an IFN-gamma-inducible immunity-related GTPase involved in pathogen clearance. C1 [Feng, Carl G.; Sher, Alan] NIAID, Parasit Dis Lab, NIH, Bethesda, MD 20892 USA. RP Feng, CG (reprint author), NIAID, Parasit Dis Lab, NIH, Bethesda, MD 20892 USA. EM cfeng@niaid.nih.gov FU Intramural NIH HHS [Z01 AI000579-19] NR 11 TC 1 Z9 1 U1 0 U2 2 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 1931-3128 J9 CELL HOST MICROBE JI Cell Host Microbe PD DEC 16 PY 2010 VL 8 IS 6 BP 463 EP 464 DI 10.1016/j.chom.2010.11.012 PG 2 WC Microbiology; Parasitology; Virology SC Microbiology; Parasitology; Virology GA 721HO UT WOS:000287344400001 PM 21147459 ER PT J AU Bergman, C Kashiwaya, Y Veech, RL AF Bergman, Christian Kashiwaya, Yoshihiro Veech, Richard L. TI The Effect of pH and Free Mg2+ on ATP Linked Enzymes and the Calculation of Gibbs Free Energy of ATP Hydrolysis SO JOURNAL OF PHYSICAL CHEMISTRY B LA English DT Article ID NICOTINAMIDE-ADENINE DINUCLEOTIDE; EQUILIBRIUM-CONSTANTS; RAT LIVER; PHYSIOLOGICAL CONDITIONS; ADENOSINE-TRIPHOSPHATE; IONIC-STRENGTH; FREE MAGNESIUM; CITRATE LYASE; REDOX STATES; PHOSPHATE AB The apparent equilibrium constants, K', of biochemical reactions containing substrates which bind [Mg2+] unequally can be significantly altered by changes in free intracellular [Mg2+]. Intracellular free [Mg2+] can be estimated by measurements of [citrate]/[isocitrate], a ratio known to vary with tissue free [Mg2+]. The combined equilibrium constant for glyceraldehyde-3-phosphate dehydrogenase, phosphoglycerate kinase, and triose phosphate isomerase for the three reactions (K'(GG-TPI)) was corrected using new binding constants for dihydroxyacetone-phosphate and 3-phosphoglycerate. The result of this calculation is demonstrated in the calculation of the free energy of ATP hydrolysis. In addition, the dependence of the equilibrium constant for the glutamine synthetase reaction on pH and free [Mg2+] was demonstrated. Furthermore, a theory linking the Delta G' value of mitochondria] complex I-II and the cytosolic Delta G' value of ATP hydrolysis is discussed with evidence from previous publications. C1 [Bergman, Christian; Kashiwaya, Yoshihiro; Veech, Richard L.] NIAAA, LMC, NIH, DHHS, Bethesda, MD 20892 USA. RP Veech, RL (reprint author), NIAAA, LMC, NIH, DHHS, 5625 Fishers Lane,Rm 2S-28, Bethesda, MD 20892 USA. EM HUrveech@mail.nih.govUH RI Bergman, Christian/D-8680-2012 NR 57 TC 7 Z9 7 U1 3 U2 22 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 1520-6106 J9 J PHYS CHEM B JI J. Phys. Chem. B PD DEC 16 PY 2010 VL 114 IS 49 BP 16137 EP 16146 DI 10.1021/jp105723r PG 10 WC Chemistry, Physical SC Chemistry GA 690GO UT WOS:000284990700013 PM 20866109 ER PT J AU Yin, H Feng, GG Clore, GM Hummer, G Rasaiah, JC AF Yin, Hao Feng, Guogang Clore, G. Marius Hummer, Gerhard Rasaiah, Jayendran C. TI Water in the Polar and Nonpolar Cavities of the Protein Interleukin-1 beta SO JOURNAL OF PHYSICAL CHEMISTRY B LA English DT Article ID HIGH-PRESSURE CRYSTALLOGRAPHY; MOLECULAR-DYNAMICS; BOUND WATER; 3-DIMENSIONAL STRUCTURE; HYDROPHOBIC CAVITY; CRYSTAL-STRUCTURE; DISORDERED WATER; NMR-SPECTROSCOPY; AQUEOUS-SOLUTION; FREE-ENERGIES AB Water in the protein interior serves important structural and functional roles and is also increasingly recognized as a relevant factor in drug binding. The nonpolar cavity in the protein interleulcin-l beta has been reported to be filled by water on the basis of some experiments and simulations and to be empty on the basis of others. Here we study the thermodynamics of filling the central nonpolar cavity and the four polar cavities of interleukin-1 beta by molecular dynamics simulation. We use different water models (TIP3P and SPC/E) and protein force fields (amber94 and amber03) to calculate the semigrand partition functions term by term that quantify the hydration equilibria. We consistently find that water in the central nonpolar cavity is thermodynamically unstable, independent of force field and water model. The apparent reason is the relatively small size of the cavity, with a volume less than 80 similar to angstrom(3). Our results are consistent with the most recent X-ray crystallographic and simulation studies but disagree with an earlier interpretation of nuclear magnetic resonance (NMR) experiments probing protein water interactions. We show that, at least semiquantitatively, the measured nuclear Overhauser effects indicating the proximity of water to the methyl groups lining the nonpolar cavity can, in all likelihood, be attributed to interactions with buried and surface water molecules near the cavity. The same methods applied to determine the occupancy of the polar cavities show that they are filled by the same number of water molecules observed in crystallography, thereby validating the theoretical and simulation methods used to study the water occupancy in the nonpolar protein cavity. C1 [Clore, G. Marius; Hummer, Gerhard] NIDDK, Chem Phys Lab, NIH, Bethesda, MD 20892 USA. [Yin, Hao; Feng, Guogang; Rasaiah, Jayendran C.] Univ Maine, Dept Chem, Orono, ME 04469 USA. RP Hummer, G (reprint author), NIDDK, Chem Phys Lab, NIH, Bethesda, MD 20892 USA. EM Gerhard.Hummer@nih.gov; rasaiah@maine.edu RI Clore, G. Marius/A-3511-2008; Hummer, Gerhard/A-2546-2013 OI Clore, G. Marius/0000-0003-3809-1027; Hummer, Gerhard/0000-0001-7768-746X FU Chemistry Division of the National Science Foundation [CHE 0549187, CHE 9961336]; NIDDK, NIH FX G.F., FI.Y., and J.C.R. were supported by grants (CHE 0549187 and CHE 9961336) from the Chemistry Division of the National Science Foundation and generous allocations of time from the University of Maine supercomputer center. G.M.C. and G.H. are supported by the Intramural Research Program of the NIDDK, NIH and acknowledge computer resources at the biowulf cluster. NR 48 TC 25 Z9 25 U1 1 U2 14 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 1520-6106 J9 J PHYS CHEM B JI J. Phys. Chem. B PD DEC 16 PY 2010 VL 114 IS 49 BP 16290 EP 16297 DI 10.1021/jp108731r PG 8 WC Chemistry, Physical SC Chemistry GA 690GO UT WOS:000284990700031 PM 21047091 ER PT J AU Antonellis, A Dennis, MY Burzynski, G Huynh, J Maduro, V Hodonsky, CJ Khajavi, M Szigeti, K Mukkamala, S Bessling, SL Pavan, WJ McCallion, AS Lupski, JR Green, ED AF Antonellis, Anthony Dennis, Megan Y. Burzynski, Grzegorz Huynh, Jimmy Maduro, Valerie Hodonsky, Chani J. Khajavi, Mehrdad Szigeti, Kinga Mukkamala, Sandeep Bessling, Seneca L. Pavan, William J. McCallion, Andrew S. Lupski, James R. Green, Eric D. CA NISC Comparative Sequencing Progra TI A Rare Myelin Protein Zero (MPZ) Variant Alters Enhancer Activity In Vitro and In Vivo SO PLOS ONE LA English DT Article ID GROWTH-RESPONSE 2; TRANSCRIPTION FACTOR SOX10; MARIE-TOOTH NEUROPATHY; FUNCTIONAL CONSEQUENCES; PERIPHERAL-NERVE; SCHWANN-CELLS; GENE; MUTATIONS; ZEBRAFISH; EGR2 AB Background: Myelin protein zero (MPZ) is a critical structural component of myelin in the peripheral nervous system. The MPZ gene is regulated, in part, by the transcription factors SOX10 and EGR2. Mutations in MPZ, SOX10, and EGR2 have been implicated in demyelinating peripheral neuropathies, suggesting that components of this transcriptional network are candidates for harboring disease-causing mutations (or otherwise functional variants) that affect MPZ expression. Methodology: We utilized a combination of multi-species sequence comparisons, transcription factor-binding site predictions, targeted human DNA re-sequencing, and in vitro and in vivo enhancer assays to study human non-coding MPZ variants. Principal Findings: Our efforts revealed a variant within the first intron of MPZ that resides within a previously described SOX10 binding site is associated with decreased enhancer activity, and alters binding of nuclear proteins. Additionally, the genomic segment harboring this variant directs tissue-relevant reporter gene expression in zebrafish. Conclusions: This is the first reported MPZ variant within a cis-acting transcriptional regulatory element. While we were unable to implicate this variant in disease onset, our data suggests that similar non-coding sequences should be screened for mutations in patients with neurological disease. Furthermore, our multi-faceted approach for examining the functional significance of non-coding variants can be readily generalized to study other loci important for myelin structure and function. C1 [Antonellis, Anthony; Hodonsky, Chani J.] Univ Michigan, Sch Med, Dept Human Genet, Ann Arbor, MI 48109 USA. [Antonellis, Anthony] Univ Michigan, Sch Med, Dept Neurol, Ann Arbor, MI USA. [Dennis, Megan Y.; Maduro, Valerie; Mukkamala, Sandeep; Green, Eric D.] NHGRI, Genome Technol Branch, NIH, Bethesda, MD 20892 USA. [Burzynski, Grzegorz; Huynh, Jimmy; Bessling, Seneca L.; McCallion, Andrew S.] Johns Hopkins Univ, Sch Med, McKusick Nathans Inst Genet Med, Baltimore, MD USA. [Burzynski, Grzegorz; Huynh, Jimmy; Bessling, Seneca L.; McCallion, Andrew S.] Johns Hopkins Univ, Sch Med, Dept Mol & Comparat Pathobiol, Baltimore, MD USA. [Khajavi, Mehrdad; Szigeti, Kinga; Lupski, James R.] Dept Mol & Human Genet, Houston, TX USA. [Szigeti, Kinga] Dept Neurol, Houston, TX USA. [Green, Eric D.; NISC Comparative Sequencing Progra] NHGRI, NIH Intramural Sequencing Ctr NISC, NIH, Bethesda, MD 20892 USA. [Pavan, William J.] NHGRI, Genet Dis Res Branch, NIH, Bethesda, MD 20892 USA. [Lupski, James R.] Baylor Coll Med, Dept Pediat, Houston, TX 77030 USA. [Lupski, James R.] Texas Childrens Hosp, Houston, TX 77030 USA. RP Antonellis, A (reprint author), Univ Michigan, Sch Med, Dept Human Genet, Ann Arbor, MI 48109 USA. EM egreen@nhgri.nih.gov FU National Human Genome Research Institute (National Institutes of Health); Charcot-Marie-Tooth Association; National Institute of General Medical Sciences [R01GM071648]; National Institute of Neurological Diseases and Stroke [R01NS062972, R00NS060983] FX This work was supported in part by the Intramural Research Program of the National Human Genome Research Institute (National Institutes of Health), a fellowship (AA) and grant (JRL) from the Charcot-Marie-Tooth Association, grant R01GM071648 from the National Institute of General Medical Sciences (ASM), grant R01NS062972 (ASM) from the National Institute of Neurological Diseases and Stroke, and grant R00NS060983 from the National Institute of Neurological Diseases and Stroke (AA). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 43 TC 6 Z9 6 U1 0 U2 1 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 185 BERRY ST, STE 1300, SAN FRANCISCO, CA 94107 USA SN 1932-6203 J9 PLOS ONE JI PLoS One PD DEC 16 PY 2010 VL 5 IS 12 AR e14346 DI 10.1371/journal.pone.0014346 PG 10 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 695OI UT WOS:000285381200004 PM 21179557 ER PT J AU Hessol, NA Napolitano, LA Smith, D Lie, Y Levine, A Young, M Cohen, M Minkoff, H Anastos, K D'Souza, G Greenblatt, RM Goedert, JJ AF Hessol, Nancy A. Napolitano, Laura A. Smith, Dawn Lie, Yolanda Levine, Alexandra Young, Mary Cohen, Mardge Minkoff, Howard Anastos, Kathryn D'Souza, Gypsyamber Greenblatt, Ruth M. Goedert, James J. TI HIV Tropism and Decreased Risk of Breast Cancer SO PLOS ONE LA English DT Article ID WOMENS INTERAGENCY HIV; IN-VITRO; CXCR4; CHEMOKINE; RECEPTOR; CELLS; INFECTION; AIDS; INHIBITION; PATHWAY AB Background: During the first two decades of the U. S. AIDS epidemic, and unlike some malignancies, breast cancer risk was significantly lower for women with human immunodeficiency virus (HIV) infection compared to the general population. This deficit in HIV-associated breast cancer could not be attributed to differences in survival, immune deficiency, childbearing or other breast cancer risk factors. HIV infects mononuclear immune cells by binding to the CD4 molecule and to CCR5 or CXCR4 chemokine coreceptors. Neoplastic breast cells commonly express CXCR4 but not CCR5. In vitro, binding HIV envelope protein to CXCR4 has been shown to induce apoptosis of neoplastic breast cells. Based on these observations, we hypothesized that breast cancer risk would be lower among women with CXCR4-tropic HIV infection. Methods and Findings: We conducted a breast cancer nested case-control study among women who participated in the WIHS and HERS HIV cohort studies with longitudinally collected risk factor data and plasma. Cases were HIV-infected women (mean age 46 years) who had stored plasma collected within 24 months of breast cancer diagnosis and an HIV viral load >= 500 copies/mL. Three HIV-infected control women, without breast cancer, were matched to each case based on age and plasma collection date. CXCR4-tropism was determined by a phenotypic tropism assay. Odds ratios (OR) and 95% confidence intervals (CI) for breast cancer were estimated by exact conditional logistic regression. Two (9%) of 23 breast cancer cases had CXCR4-tropic HIV, compared to 19 (28%) of 69 matched controls. Breast cancer risk was significantly and independently reduced with CXCR4 tropism (adjusted odds ratio, 0.10, 95% CI 0.002-0.84) and with menopause (adjusted odds ratio, 0.08, 95% CI 0.001-0.83). Adjustment for CD4(+) cell count, HIV viral load, and use of antiretroviral therapy did not attenuate the association between infection with CXCR4-tropic HIV and breast cancer. Conclusions: Low breast cancer risk with HIV is specifically linked to CXCR4-using variants of HIV. These variants are thought to exclusively bind to and signal through a receptor that is commonly expressed on hyperplastic and neoplastic breast duct cells. Additional studies are needed to confirm these observations and to understand how CXCR4 might reduce breast cancer risk. C1 [Hessol, Nancy A.; Greenblatt, Ruth M.] Univ Calif San Francisco, Dept Clin Pharm, San Francisco, CA 94143 USA. [Napolitano, Laura A.; Lie, Yolanda] Monogram Biosci, San Francisco, CA USA. [Napolitano, Laura A.] Univ Calif San Francisco, Dept Med, San Francisco, CA USA. [Smith, Dawn] Ctr Dis Control & Prevent, Atlanta, GA USA. [Levine, Alexandra] City Hope Natl Med Ctr, Duarte, CA 91010 USA. [Young, Mary] Georgetown Univ, Sch Med, Washington, DC USA. [Cohen, Mardge] Rush Univ, Dept Med, Chicago, IL 60612 USA. [Cohen, Mardge] Rush Univ, Stroger Hosp, Chicago, IL 60612 USA. [Minkoff, Howard] SUNY Hlth Sci Ctr, Brooklyn, NY 11203 USA. [Minkoff, Howard] Maimonides Hosp, Brooklyn, NY 11219 USA. [Anastos, Kathryn] Montefiore Med Ctr, Bronx, NY 10467 USA. [D'Souza, Gypsyamber] Johns Hopkins Sch Publ Hlth, Baltimore, MD USA. [Goedert, James J.] NCI, Infect & Immunoepidemiol Branch, Div Canc Epidemiol & Genet, NIH, Bethesda, MD 20892 USA. [Levine, Alexandra] Univ So Calif, Keck Sch Med, Los Angeles, CA 90033 USA. RP Hessol, NA (reprint author), Univ Calif San Francisco, Dept Clin Pharm, San Francisco, CA 94143 USA. EM goedertj@mail.nih.gov FU National Institutes of Health; Centers for Disease Control and Prevention; National Institute of Allergy and Infectious Diseases [UO1-AI-35004, UO1-AI-31834, UO1-AI-34994, UO1-AI-34989, UO1-AI-34993, UO1-AI-42590]; Eunice Kennedy Shriver National Institute of Child Health and Human Development [UO1-HD-32632]; National Cancer Institute; National Institute on Drug Abuse; National Institute on Deafness and Other Communication Disorders; National Center for Research Resources (UCSF-CTSI) [UL1 RR024131]; Centers for Disease Control and Prevention [U64/CCU106795, U64/CCU206798, U64/CCU306802, U64/CCU506831] FX Funded in part by the Intramural Research Program of the National Cancer Institute (JJG), by other components of the National Institutes of Health, and by the Centers for Disease Control and Prevention. The WIHS is funded by the National Institute of Allergy and Infectious Diseases (UO1-AI-35004, UO1-AI-31834, UO1-AI-34994, UO1-AI-34989, UO1-AI-34993, and UO1-AI-42590) and by the Eunice Kennedy Shriver National Institute of Child Health and Human Development (UO1-HD-32632). The WIHS is co-funded by the National Cancer Institute, the National Institute on Drug Abuse, and the National Institute on Deafness and Other Communication Disorders. Funding is also provided by the National Center for Research Resources (UCSF-CTSI Grant Number UL1 RR024131). The HIV Epidemiology Research Study (HERS) was funded through Centers for Disease Control and Prevention cooperative agreements U64/CCU106795, U64/CCU206798, U64/CCU306802, and U64/CCU506831. Monogram Biosciences supported tropism testing and all assays were performed by the Monogram Clinical Reference Laboratory. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 29 TC 13 Z9 13 U1 0 U2 5 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 185 BERRY ST, STE 1300, SAN FRANCISCO, CA 94107 USA SN 1932-6203 J9 PLOS ONE JI PLoS One PD DEC 16 PY 2010 VL 5 IS 12 AR e14349 DI 10.1371/journal.pone.0014349 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 695OI UT WOS:000285381200006 PM 21179547 ER PT J AU Ledgerwood, JE Costner, P Desai, N Holman, L Enama, ME Yamshchikov, G Mulangu, S Hu, Z Andrews, CA Sheets, RA Koup, RA Roederer, M Bailer, R Mascola, JR Pau, MG Sullivan, NJ Goudsmit, J Nabel, GJ Graham, BS AF Ledgerwood, J. E. Costner, P. Desai, N. Holman, L. Enama, M. E. Yamshchikov, G. Mulangu, S. Hu, Z. Andrews, C. A. Sheets, R. A. Koup, R. A. Roederer, M. Bailer, R. Mascola, J. R. Pau, M. G. Sullivan, N. J. Goudsmit, J. Nabel, G. J. Graham, B. S. CA VRC 205 Study Team TI A replication defective recombinant Ad5 vaccine expressing Ebola virus GP is safe and immunogenic in healthy adults SO VACCINE LA English DT Article DE Adenovirus; Gene-based vaccines; Ebola; Filovirus vaccine ID TYPE-1 GAG GENE; ADENOVIRUS VECTORS; NONHUMAN-PRIMATES; HIV-1 VACCINE; OF-CONCEPT; CANDIDATE VACCINE; HEMORRHAGIC-FEVER; INDUCED IMMUNITY; PHASE-1 SAFETY; RHESUS-MONKEYS AB Ebola virus causes irregular outbreaks of severe hemorrhagic fever in equatorial Africa. Case mortality remains high; there is no effective treatment and outbreaks are sporadic and unpredictable. Studies of Ebola virus vaccine platforms in non-human primates have established that the induction of protective immunity is possible and safety and human immunogenicity has been demonstrated in a previous Phase I clinical trial of a 1st generation Ebola DNA vaccine. We now report the safety and immunogenicity of a recombinant adenovirus serotype 5 (rAd5) vaccine encoding the envelope glycoprotein (GP) from the Zaire and Sudan Ebola virus species, in a randomized, placebo-controlled, double-blinded, dose escalation, Phase I human study. Thirty-one healthy adults received vaccine at 2 x 10(9) (n = 12), or 2 x 10(10) (n = 11) viral particles or placebo (n = 8) as an intramuscular injection. Antibody responses were assessed by ELISA and neutralizing assays; and T cell responses were assessed by ELISpot and intracellular cytokine staining assays. This recombinant Ebola virus vaccine was safe and subjects developed antigen specific humoral and cellular immune responses. Published by Elsevier Ltd. C1 [Ledgerwood, J. E.; Costner, P.; Desai, N.; Holman, L.; Enama, M. E.; Yamshchikov, G.; Mulangu, S.; Hu, Z.; Andrews, C. A.; Sheets, R. A.; Koup, R. A.; Roederer, M.; Bailer, R.; Mascola, J. R.; Sullivan, N. J.; Nabel, G. J.; Graham, B. S.] NIAID, Vaccine Res Ctr, NIH, Bethesda, MD 20892 USA. [Pau, M. G.; Goudsmit, J.] Crucell Holland BV, Leiden, Netherlands. RP Ledgerwood, JE (reprint author), NIAID, Vaccine Res Ctr, NIH, 9000 Rockville Pike,Bldg 10,CRC,Room 5-2440,40 Co, Bethesda, MD 20892 USA. EM Ledgerwood@mail.nih.gov NR 47 TC 76 Z9 82 U1 1 U2 26 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 DEC 16 PY 2010 VL 29 IS 2 BP 304 EP 313 DI 10.1016/j.vaccine.2010.10.037 PG 10 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA 717OM UT WOS:000287057300019 PM 21034824 ER PT J AU Keyes, KM Hatzenbuehler, ML McLaughlin, KA Link, B Olfson, M Grant, BF Hasin, D AF Keyes, K. M. Hatzenbuehler, M. L. McLaughlin, K. A. Link, B. Olfson, M. Grant, B. F. Hasin, D. TI Stigma and Treatment for Alcohol Disorders in the United States SO AMERICAN JOURNAL OF EPIDEMIOLOGY LA English DT Article DE alcohol drinking; alcoholics anonymous; alcoholism; mental disorders; psychiatric therapeutic processes; shame; therapeutics; United States ID SUBSTANCE USE DISORDERS; NATIONAL EPIDEMIOLOGIC SURVEY; INTERVIEW SCHEDULE AUDADIS; GENERAL-POPULATION SAMPLE; PSYCHIATRIC DIAGNOSTIC MODULES; SERIOUS MENTAL-ILLNESS; DSM-IV ALCOHOL; SERVICE UTILIZATION; PERCEIVED STIGMA; SOCIAL DISTANCE AB Among a nationally representative sample of adults with an alcohol use disorder, the authors tested whether perceived stigmatization of alcoholism was associated with a lower likelihood of receiving alcohol-related services. Data were drawn from a face-to-face epidemiologic survey of 34,653 adults interviewed in 2004-2005 who were aged 20 years or older and residing in households and group quarters in the United States. Alcohol abuse/dependence was diagnosed by using the Alcohol Use Disorder and Associated Disabilities Interview Schedule-Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, version (AUDADIS-IV). The stigma measure used was the Perceived Devaluation-Discrimination Scale. The main outcome was lifetime intervention including professional services and 12-step groups for alcohol disorders. Individuals with a lifetime diagnosis of an alcohol use disorder were less likely to utilize alcohol services if they perceived higher stigma toward individuals with alcohol disorders (odds ratio = 0.37, 95% confidence interval: 0.18, 0.76). Higher perceived stigma was associated with male gender (beta = -0.75; P < 0.01), nonwhite compared with non-Hispanic white race/ethnicity, lower income (beta = 1.0; P < 0.01), education (beta = 1.48; P < 0.01), and being previously married (beta = 0.47; P = 0.02). Individuals reporting close contact with an alcohol-disordered individual (e.g., relative with an alcohol problem) reported lower perceived stigma (beta = -1.70; P < 0.01). A link between highly stigmatized views of alcoholism and lack of services suggests that stigma reduction should be integrated into public health efforts to promote alcohol treatment. C1 [Keyes, K. M.] Columbia Univ, Dept Epidemiol, Mailman Sch Publ Hlth, New York, NY 10032 USA. [Keyes, K. M.; Link, B.; Olfson, M.; Hasin, D.] New York State Psychiat Inst & Hosp, New York, NY 10032 USA. [Hatzenbuehler, M. L.] Yale Univ, Dept Psychol, New Haven, CT 06520 USA. [McLaughlin, K. A.] Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA. [Grant, B. F.] NIAAA, Lab Epidemiol & Biometry, Div Intramural Clin & Biol Res, NIH,Dept Hlth & Human Serv, Bethesda, MD USA. [Hasin, D.] Columbia Univ, Dept Psychiat, Coll Phys & Surg, New York, NY USA. RP Keyes, KM (reprint author), Columbia Univ, Dept Epidemiol, Mailman Sch Publ Hlth, 722 W 168th St, New York, NY 10032 USA. EM kmk2104@columbia.edu RI Link, Bruce/N-9087-2013; OI Link, Bruce/0000-0001-9980-7450; McLaughlin, Katie/0000-0002-1362-2410 FU National Institute on Alcoholism and Alcohol Abuse [K05 AA014223]; National Institute on Drug Abuse [RO1 DA018652, R21 DA020667, F31-DA026689]; New York State Psychiatric Institute FX This research was supported in part by grants from the National Institute on Alcoholism and Alcohol Abuse (K05 AA014223 to D. H.), the National Institute on Drug Abuse (RO1 DA018652 to D. H.; R21 DA020667), a fellowship from the National Institute of Drug Abuse (F31-DA026689 to K. M. K.), and support from the New York State Psychiatric Institute. NR 87 TC 83 Z9 84 U1 3 U2 30 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0002-9262 J9 AM J EPIDEMIOL JI Am. J. Epidemiol. PD DEC 15 PY 2010 VL 172 IS 12 BP 1364 EP 1372 DI 10.1093/aje/kwq304 PG 9 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 692ZA UT WOS:000285193200007 PM 21044992 ER PT J AU Martin, WJ Brynes, S Walsh, JW AF Martin, William J., II Brynes, Sue Walsh, John W. TI Chilean Miners and Biomedical Research A Modest Proposal SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Editorial Material C1 [Martin, William J., II] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Lab Acute Lung Injury & Repair, Bethesda, MD USA. [Brynes, Sue] LAM Fdn, Cincinnati, OH USA. [Walsh, John W.] Alpha One Fdn, Miami, FL USA. RP Martin, WJ (reprint author), Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Lab Acute Lung Injury & Repair, Bethesda, MD USA. NR 2 TC 1 Z9 1 U1 0 U2 2 PU AMER THORACIC SOC PI NEW YORK PA 61 BROADWAY, FL 4, NEW YORK, NY 10006 USA SN 1073-449X J9 AM J RESP CRIT CARE JI Am. J. Respir. Crit. Care Med. PD DEC 15 PY 2010 VL 182 IS 12 BP 1459 EP 1460 DI 10.1164/rccm.201010-1694ED PG 2 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA 697RU UT WOS:000285534600001 PM 21159901 ER PT J AU Erzurum, S Rounds, SI Stevens, T Aldred, M Aliotta, J Archer, SL Asosingh, K Balaban, R Bauer, N Bhattacharya, J Bogaard, H Choudhary, G Dorn, GW Dweik, R Fagan, K Fallon, M Finkel, T Geraci, M Gladwin, MT Hassoun, PM Humbert, M Kaminski, N Kawut, SM Loscalzo, J McDonald, D McMurtry, IF Newman, J Nicolls, M Rabinovitch, M Shizuru, J Oka, M Polgar, P Rodman, D Schumacker, P Stenmark, K Tuder, R Voelkel, N Sullivan, E Weinshilboum, R Yoder, MC Zhao, YM Gail, D Moore, TM AF Erzurum, Serpil Rounds, Sharon I. Stevens, Troy Aldred, Micheala Aliotta, Jason Archer, Stephen L. Asosingh, Kewal Balaban, Robert Bauer, Natalie Bhattacharya, Jahar Bogaard, Harm Choudhary, Gaurav Dorn, Gerald W., II Dweik, Raed Fagan, Karen Fallon, Michael Finkel, Toren Geraci, Mark Gladwin, Mark T. Hassoun, Paul M. Humbert, Marc Kaminski, Naftali Kawut, Steven M. Loscalzo, Joseph McDonald, Donald McMurtry, Ivan F. Newman, John Nicolls, Mark Rabinovitch, Marlene Shizuru, Judy Oka, Masahiko Polgar, Peter Rodman, David Schumacker, Paul Stenmark, Kurt Tuder, Rubin Voelkel, Norbert Sullivan, Eugene Weinshilboum, Richard Yoder, Mervin C. Zhao, Yingming Gail, Dorothy Moore, Timothy M. TI Strategic Plan for Lung Vascular Research An NHLBI-ORDR Workshop Report SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Article DE right ventricle; pulmonary hypertension; metabolism; genomics; phenotyping ID PULMONARY ARTERIAL-HYPERTENSION; HEREDITARY HEMORRHAGIC TELANGIECTASIA; ENDOTHELIAL PROGENITOR CELLS; RIGHT-VENTRICULAR FUNCTION; GENE MICROARRAY ANALYSIS; RIGHT-HEART-FAILURE; HEPATOPULMONARY SYNDROME; MOLECULAR-MECHANISMS; DRUG-THERAPY; END-POINTS AB The Division of Lung Diseases of the National Heart, Lung, and Blood Institute, with the Office of Rare Diseases Research, held a workshop to identify priority areas and strategic goals to enhance and accelerate research that will result in improved understanding of the lung vasculature, translational research needs, and ultimately the care of patients with pulmonary vascular diseases. Multidisciplinary experts with diverse experience in laboratory, translational, and clinical studies identified seven priority areas and discussed limitations in our current knowledge, technologies, and approaches. The focus for future research efforts include the following: (1) better characterizing vascular genotype phenotype relationships and incorporating systems biology approaches when appropriate; (2) advancing our understanding of pulmonary vascular metabolic regulatory signaling in health and disease; (3) expanding our knowledge of the biologic relationships between the lung circulation and circulating elements, systemic vascular function, and right heart function and disease; (4) improving translational research for identifying disease-modifying therapies for the pulmonary hypertensive diseases; (5) establishing an appropriate and effective platform for advancing translational findings into clinical studies testing; and (6) developing the specific technologies and tools that will be enabling for these goals, such as question-guided imaging techniques and lung vascular investigator training programs. Recommendations from this workshop will be used within the Lung Vascular Biology and Disease Extramural Research Program for planning and strategic implementation purposes. C1 [Moore, Timothy M.] NHLBI, Div Lung Dis, NIH, Bethesda, MD 20892 USA. [Erzurum, Serpil; Asosingh, Kewal; Dweik, Raed] Cleveland Clin, Dept Pathobiol, Cleveland, OH 44106 USA. [Rounds, Sharon I.; Choudhary, Gaurav] Brown Univ, Dept Med, Providence Vet Affairs Med Ctr, Warren Alpert Med Sch, Providence, RI 02912 USA. [Stevens, Troy; Bauer, Natalie; Fagan, Karen; McMurtry, Ivan F.; Oka, Masahiko] Univ S Alabama, Ctr Lung Biol, Mobile, AL 36688 USA. [Aliotta, Jason] Brown Univ, Dept Med, Div Pulm Sleep & Crit Care Med, Warren Alpert Med Sch, Providence, RI 02912 USA. [Archer, Stephen L.] Univ Chicago, Dept Med, Cardiol Sect, Chicago, IL 60637 USA. [Balaban, Robert] NHLBI, Cardiac Energet Lab, Bethesda, MD 20892 USA. [Bhattacharya, Jahar] Columbia Univ Coll Phys & Surg, Dept Med, New York, NY 10032 USA. [Bhattacharya, Jahar] Columbia Univ Coll Phys & Surg, Dept Physiol & Cellular Biophys, New York, NY 10032 USA. [Bogaard, Harm; Voelkel, Norbert] Virginia Commonwealth Univ, Dept Med, Div Pulm & Crit Care Med, Richmond, VA 23298 USA. [Dorn, Gerald W., II] Washington Univ, Sch Med, Dept Internal Med, St Louis, MO 63110 USA. [Dorn, Gerald W., II] Washington Univ, Sch Med, Ctr Pharmacogenom, St Louis, MO USA. [Fallon, Michael] Univ Texas Hlth Sci Ctr Houston, Sch Med, Dept Med, Div Gastroenterol Hepatol & Nutr, Houston, TX USA. [Finkel, Toren] NHLBI, Translat Med Branch, Bethesda, MD 20892 USA. [Geraci, Mark; Tuder, Rubin] Univ Colorado, Dept Med, Denver, CO USA. [Gladwin, Mark T.; Kaminski, Naftali] Univ Pittsburgh, Sch Med, Dept Med, Div Pulm Allergy & Crit Care Med, Pittsburgh, PA USA. [Gladwin, Mark T.; Kaminski, Naftali] Univ Pittsburgh, Sch Med, Vasc Med Inst, Pittsburgh, PA USA. [Hassoun, Paul M.] Johns Hopkins Univ, Div Pulm & Crit Care Med, Dept Med, Baltimore, MD USA. [Humbert, Marc] Univ Paris 11, Hop Antoine Beclere, Paris, France. [Kawut, Steven M.] Univ Penn, Sch Med, Dept Med, Philadelphia, PA 19104 USA. [Loscalzo, Joseph] Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Med, Boston, MA 02115 USA. [McDonald, Donald] Univ Calif San Francisco, Dept Anat, San Francisco, CA 94143 USA. [Newman, John] Vanderbilt Univ Sch Med, Dept Allergy Pulm & Crit Med, Nashville, TN USA. [Nicolls, Mark] Stanford Univ, Dept Med, Sch Med, Div Pulm & Crit Care, Stanford, CA 94305 USA. [Rabinovitch, Marlene] Stanford Univ, Vera Moulton Wall Ctr Pulm Vasc Dis, Sch Med, Stanford, CA 94305 USA. [Shizuru, Judy] Stanford Univ, Dept Med Blood & Marrow Transplantat, Sch Med, Stanford, CA 94305 USA. [Polgar, Peter] Boston Univ, Sch Med, Dept Biochem, Boston, MA 02118 USA. [Rodman, David] Novartis Inst Biomed Res, Cambridge, MA USA. [Schumacker, Paul] Northwestern Univ, Dept Pediat, Chicago, IL 60611 USA. [Stenmark, Kurt] Univ Colorado, Dept Pediat, Denver, CO 80202 USA. [Sullivan, Eugene] United Therapeut, Silver Spring, MD USA. [Weinshilboum, Richard] Mayo Clin, Mayo Med Sch, Dept Mol Pharmacol & Expt Therapeut & Med, Rochester, MN USA. [Yoder, Mervin C.] Indiana Univ Sch Med, Dept Pediat, Indianapolis, IN USA. [Zhao, Yingming] Univ Chicago, Ben May Dept Canc Res, Chicago, IL 60637 USA. RP Moore, TM (reprint author), NHLBI, Div Lung Dis, NIH, 6701 Rockledge Dr,Rockledge Ctr 2,Room 10182, Bethesda, MD 20892 USA. EM mooretm@mail.nih.gov RI Archer, Stephen/C-3621-2013; OI Polgar, Peter/0000-0002-9112-1101 FU Division of Lung Diseases, National Heart, Lung, and Blood Institute, NIH, Office of Rare Diseases Research, Office of the Director, NIH FX Supported by the Division of Lung Diseases, National Heart, Lung, and Blood Institute, NIH, Office of Rare Diseases Research, Office of the Director, NIH. NR 74 TC 27 Z9 27 U1 0 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 DEC 15 PY 2010 VL 182 IS 12 BP 1554 EP 1562 DI 10.1164/rccm.201006-0869WS PG 9 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA 697RU UT WOS:000285534600016 PM 20833821 ER PT J AU Vangala, K Yanney, M Hsiao, CT Wu, WW Shen, RF Zou, SG Sygula, A Zhang, DM AF Vangala, Karthikeshwar Yanney, Michael Hsiao, Cheng-Te Wu, Wells W. Shen, Rong-Fong Zou, Sige Sygula, Andrzej Zhang, Dongmao TI Sensitive Carbohydrate Detection Using Surface Enhanced Raman Tagging SO ANALYTICAL CHEMISTRY LA English DT Article ID ASSISTED-LASER-DESORPTION/IONIZATION; MASS-SPECTROMETRY; SILVER NANOPARTICLES; SCATTERING; PROTEIN; QUANTIFICATION; GOLD; OLIGOSACCHARIDES; DERIVATIZATION; SPECTROSCOPY AB Glycomic analysis is an increasingly important field in biological and biomedical research as glycosylation is one of the most important protein post-translational modifications. We have developed a new technique to detect carbohydrates using surface enhanced Raman spectroscopy (SERS) by designing and applying a Rhodamine B derivative as the SERS tag. Using a reductive amination reaction, the Rhodamine-based tag (RT) was successfully conjugated to three model carbohydrates (glucose, lactose, and glucuronic acid). SERS detection limits obtained with a 633 nm HeNe laser were similar to 1 nM in concentration for all the RT-carbohydrate conjugates and similar to 10 fmol in total sample consumption. The dynamic range of the SERS method is about 4 orders of magnitude, spanning from 1 nM to 5 mu M. Ratiometric SERS quantification using isotope-substituted SERS internal references allows comparative quantifications of carbohydrates labeled with RT and deuterium/hydrogen substituted RT tags, respectively. In addition to enhancing the SERS detection of the tagged carbohydrates, the Rhodamine tagging facilitates fluorescence and mass spectrometric detection of carbohydrates. Current fluorescence sensitivity of RT-carbohydrates is similar to 3 nM in concentration while the mass spectrometry (MS) sensitivity is about 1 fmol, achieved with a linear ion trap electrospray ionization (ESI)-MS instrument. Potential applications that take advantage of the high SERS, fluorescence, and MS sensitivity of this SERS tagging strategy are discussed for practical glycomic analysis where carbohydrates may be quantified with a fluorescence and SERS technique and then identified with ESI-MS techniques. C1 [Vangala, Karthikeshwar; Yanney, Michael; Sygula, Andrzej; Zhang, Dongmao] Mississippi State Univ, Dept Chem, Mississippi State, MS 39762 USA. [Hsiao, Cheng-Te; Zou, Sige] NIA, Lab Expt Gerontol, NIH, Baltimore, MD 21224 USA. [Wu, Wells W.; Shen, Rong-Fong] NIA, Prote & Analyt Biochem Unit, NIH, Baltimore, MD 21224 USA. RP Zhang, DM (reprint author), Mississippi State Univ, Dept Chem, Mississippi State, MS 39762 USA. EM dz33@msstate.edu FU Department of Chemistry at Mississippi State University; MSU; National Institute on Aging FX D.Z. thanks Dr. Ed Lewis for allowing the use of the fluorimeter for the fluorescence measurement. This work was supported by start-up funding from the Department of Chemistry at Mississippi State University and a Research Initiation Proposal Award from MSU provided to D.Z. and in part by the Intramural Research Program of the National Institute on Aging to S.Z. and R.-F.S. NR 48 TC 19 Z9 21 U1 7 U2 83 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0003-2700 J9 ANAL CHEM JI Anal. Chem. PD DEC 15 PY 2010 VL 82 IS 24 BP 10164 EP 10171 DI 10.1021/ac102284x PG 8 WC Chemistry, Analytical SC Chemistry GA 693HS UT WOS:000285215800029 PM 21082777 ER PT J AU Lee, KM Lee, KW Jung, SK Lee, EJ Heo, YS Bode, AM Lubet, RA Lee, HJ Dong, ZG AF Lee, Kyung Mi Lee, Ki Won Jung, Sung Keun Lee, Eun Jung Heo, Yong-Seok Bode, Ann M. Lubet, Ronald A. Lee, Hyong Joo Dong, Zigang TI Kaempferol inhibits UVB-induced COX-2 expression by suppressing Src kinase activity SO BIOCHEMICAL PHARMACOLOGY LA English DT Article DE Flavonoid; Photo-carcinogenesis; Skin cancer ID NONMELANOMA SKIN-CANCER; C-SRC; MAP KINASE; MOUSE SKIN; CARCINOGENESIS; ACTIVATION; CYCLOOXYGENASE-2; FLAVONOIDS; RADIATION; CELLS AB Ultraviolet (UV) radiation is the primary environmental risk factor in the development of nonmelanoma skin cancer, and UVB in particular promotes tumor growth through various signaling pathways. Kaempferol, a flavonoid with anti-inflammatory and anti-oxidative properties, has been studied as a chemopreventive agent; however, little is known regarding its effects on UVB-induced photo-carcinogenesis. Here, we examined the effect of kaempferol on UVB-induced skin inflammation. We found that kaempferol suppressed UVB-induced cyclooxygenase-2 (COX-2) protein expression in mouse skin epidermal JB6 P+ cells and attenuated the UVB-induced transcriptional activities of cox-2 and activator protein-1 (AP-1). Kaempferol attenuated the UVB-induced phosphorylation of several mitogen-activated protein kinases (MAPKs), including ERKs, p38, and JNKs, but had no effect on the phosphorylation of the upstream MAPK regulator Src. However, in vitro and ex vivo kinase assays demonstrated that kaempferol suppressed Src kinase activity. Furthermore, in vivo data from mouse skin support the idea that kaempferol suppresses UVB-induced COX-2 expression by blocking Src kinase activity. A pull-down assay revealed that kaempferol competes with ATP for direct binding to Src. Docking data suggest that kaempferol docks easily into the ATP-binding site of Src, which is located between the N and the C lobes of the kinase domain. Taken together, these results suggest that kaempferol is a potent chemopreventive agent against skin cancer through its inhibitory interaction with Src. (C) 2010 Elsevier Inc. All rights reserved. C1 [Lee, Kyung Mi; Jung, Sung Keun; Lee, Eun Jung; Lee, Hyong Joo] Seoul Natl Univ, Dept Agr Biotechnol, Seoul 151921, South Korea. [Lee, Kyung Mi; Lee, Ki Won; Jung, Sung Keun; Bode, Ann M.; Dong, Zigang] Univ Minnesota, Hormel Inst, Austin, MN 55912 USA. [Lee, Kyung Mi; Lee, Ki Won] Konkuk Univ, Biomol Informat Ctr, Dept Biosci & Biotechnol, Seoul 143701, South Korea. [Heo, Yong-Seok] Konkuk Univ, Dept Chem, Seoul 143701, South Korea. [Lubet, Ronald A.] NCI, Div Canc Prevent & Control, Rockville, MD 20852 USA. RP Lee, HJ (reprint author), Seoul Natl Univ, Dept Agr Biotechnol, Seoul 151921, South Korea. EM leehyjo@snu.ac.kr; zgdong@hi.umn.edu RI Heo, Yong-Seok/D-8244-2011 FU World Class University, World Class Institute [R31-2008-00-10056-0]; Priority Research Centers Program [2009-0093824]; National Research Foundation of Korea; National Cancer Institute [N01-CN-53301 WA#14] FX This study was supported by the World Class University Program (R31-2008-00-10056-0), World Class Institute Program; and Priority Research Centers Program (2009-0093824), the National Research Foundation of Korea and National Cancer Institute (N01-CN-53301 WA#14). NR 44 TC 45 Z9 49 U1 1 U2 4 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0006-2952 J9 BIOCHEM PHARMACOL JI Biochem. Pharmacol. PD DEC 15 PY 2010 VL 80 IS 12 SI SI BP 2042 EP 2049 DI 10.1016/j.bcp.2010.06.042 PG 8 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 679RB UT WOS:000284177400028 PM 20599768 ER PT J AU Liu, B Liu, L Tsykin, A Goodall, GJ Green, JE Zhu, M Kim, CH Li, JY AF Liu, Bing Liu, Lin Tsykin, Anna Goodall, Gregory J. Green, Jeffrey E. Zhu, Min Kim, Chang Hee Li, Jiuyong TI Identifying functional miRNA-mRNA regulatory modules with correspondence latent dirichlet allocation SO BIOINFORMATICS LA English DT Article ID HUMAN BREAST-CANCER; MICRORNA TARGETS; IDENTIFICATION; PREDICTION; DISCOVERY; PATTERNS; SUBTYPES; GENES AB Motivation: MicroRNAs ( miRNAs) are small non-coding RNAs that cause mRNA degradation and translational inhibition. They are important regulators of development and cellular homeostasis through their control of diverse processes. Recently, great efforts have been made to elucidate their regulatory mechanism, but the functions of most miRNAs and their precise regulatory mechanisms remain elusive. With more and more matched expression profiles of miRNAs and mRNAs having been made available, it is of great interest to utilize both expression profiles to discover the functional regulatory networks of miRNAs and their target mRNAs for potential biological processes that they may participate in. Results: We present a probabilistic graphical model to discover functional miRNA regulatory modules at potential biological levels by integrating heterogeneous datasets, including expression profiles of miRNAs and mRNAs, with or without the prior target binding information. We applied this model to a mouse mammary dataset. It effectively captured several biological process specific modules involving miRNAs and their target mRNAs. Furthermore, without using prior target binding information, the identified miRNAs and mRNAs in each module show a large proportion of overlap with predicted miRNA target relationships, suggesting that expression profiles are crucial for both target identification and discovery of regulatory modules. C1 [Liu, Bing; Liu, Lin; Li, Jiuyong] Univ S Australia, Sch Comp & Informat Sci, Mawson Lakes, SA 5095, Australia. [Liu, Bing; Tsykin, Anna; Goodall, Gregory J.] SA Pathol, Ctr Canc Biol, Adelaide, SA 5000, Australia. [Tsykin, Anna] Univ Adelaide, Sch Mol & Biomed Sci, Adelaide, SA 5005, Australia. [Goodall, Gregory J.] Univ Adelaide, Dept Med, Adelaide, SA 5005, Australia. [Green, Jeffrey E.; Zhu, Min] NCI, Lab Canc Biol & Genet, Bethesda, MD 20892 USA. [Kim, Chang Hee] NCI, Lab Mol Technol, FCRDC, Frederick, MD 21702 USA. RP Li, JY (reprint author), Univ S Australia, Sch Comp & Informat Sci, Mawson Lakes, SA 5095, Australia. RI Liu, Bing/E-5854-2013; Li, Jiuyong/A-8134-2008; OI Li, Jiuyong/0000-0002-9023-1878; Tsykin, Anna/0000-0001-5965-6803 FU Center for Cancer Research, NIH, Bethesda, MD, USA FX Funding: Intramural Program, Center for Cancer Research, NIH, Bethesda, MD, USA (in part). NR 36 TC 49 Z9 51 U1 1 U2 18 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 1367-4803 J9 BIOINFORMATICS JI Bioinformatics PD DEC 15 PY 2010 VL 26 IS 24 BP 3105 EP 3111 DI 10.1093/bioinformatics/btq576 PG 7 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 689RY UT WOS:000284947700014 PM 20956247 ER PT J AU Abazyan, B Nomura, J Kannan, G Ishizuka, K Tamashiro, KL Nucifora, F Pogorelov, V Ladenheim, B Yang, CX Krasnova, IN Cadet, JL Pardo, C Mori, S Kamiya, A Vogel, MW Sawa, A Ross, CA Pletnikov, MV AF Abazyan, Bagrat Nomura, Jun Kannan, Geetha Ishizuka, Koko Tamashiro, Kellie L. Nucifora, Frederick Pogorelov, Vladimir Ladenheim, Bruce Yang, Chunxia Krasnova, Irina N. Cadet, Jean Lud Pardo, Carlos Mori, Susumu Kamiya, Atsushi Vogel, Michael W. Sawa, Akira Ross, Christopher A. Pletnikov, Mikhail V. TI Prenatal Interaction of Mutant DISC1 and Immune Activation Produces Adult Psychopathology SO BIOLOGICAL PSYCHIATRY LA English DT Article DE DISC1; gene-environment interactions; mood disorders; mouse models; schizophrenia; Tet-off system ID DENDRITIC SPINE DENSITY; GENE-ENVIRONMENT INTERACTIONS; BIPOLAR DISORDER; MOOD DISORDERS; BEHAVIORAL PHENOTYPES; INDUCIBLE EXPRESSION; SCHIZOPHRENIA RISK; PREFRONTAL CORTEX; GENOMIC STRUCTURE; INFECTION AB Background: Gene-environment interactions (GEI) are involved in the pathogenesis of mental diseases. We evaluated interaction between mutant human disrupted-in-schizophrenia 1 (mhDISC1) and maternal immune activation implicated in schizophrenia and mood disorders. Methods: Pregnant mice were treated with saline or polyinosinic: polycytidylic acid at gestation day 9. Levels of inflammatory cytokines were measured in fetal and adult brains; expression of mhDISC1, endogenous DISC1, lissencephaly type 1, nuclear distribution protein nudE-like 1, glycoprotein 130, growth factor receptor-bound protein 2, and glycogen synthase kinase-3beta were assessed in cortical samples of newborn mice. Tissue content of monoamines, volumetric brain abnormalities, dendritic spine density in the hippocampus, and various domains of the mouse behavior repertoire were evaluated in adult male mice. Results: Prenatal interaction produced anxiety, depression-like responses, and altered social behavior that were accompanied by decreased reactivity of the hypothalamic-pituitary-adrenal axis, attenuated serotonin neurotransmission in the hippocampus, reduced enlargement of lateral ventricles, decreased volumes of amygdala and periaqueductal gray matter and density of spines on dendrites of granule cells of the hippocampus. Prenatal interaction modulated secretion of inflammatory cytokines in fetal brains, levels of mhDISC1, endogenous mouse DISC1, and glycogen synthase kinase-3beta. The behavioral effects of GEI were observed only if mhDISC1 was expressed throughout the life span. Conclusions: Prenatal immune activation interacted with mhDISC1 to produce the neurobehavioral phenotypes that were not seen in untreated mhDISC1 mice and that resemble aspects of major mental illnesses. Our DISC1 mouse model is a valuable system to study GEI relevant to mental illnesses. C1 [Abazyan, Bagrat; Nomura, Jun; Kannan, Geetha; Nucifora, Frederick; Pogorelov, Vladimir; Yang, Chunxia; Ross, Christopher A.; Pletnikov, Mikhail V.] Johns Hopkins Univ, Sch Med, Dept Psychiat & Behav Sci, Div Neurobiol, Baltimore, MD 21287 USA. [Pardo, Carlos; Mori, Susumu; Ross, Christopher A.] Johns Hopkins Univ, Sch Med, Dept Neurol, Baltimore, MD 21287 USA. [Sawa, Akira; Ross, Christopher A.; Pletnikov, Mikhail V.] Johns Hopkins Univ, Sch Med, Dept Neurosci, Baltimore, MD 21287 USA. [Mori, Susumu] Johns Hopkins Univ, Sch Med, Dept Radiol, Baltimore, MD 21287 USA. [Ross, Christopher A.] Johns Hopkins Univ, Sch Med, Dept Pharmacol, Baltimore, MD 21287 USA. [Pletnikov, Mikhail V.] Johns Hopkins Univ, Sch Med, Dept Mol & Comparat Pathobiol, Baltimore, MD 21287 USA. [Kannan, Geetha; Sawa, Akira; Ross, Christopher A.; Pletnikov, Mikhail V.] Johns Hopkins Univ, Sch Med, Program Cellular & Mol Med, Baltimore, MD 21287 USA. [Ishizuka, Koko; Kamiya, Atsushi; Sawa, Akira] Johns Hopkins Univ, Sch Med, Program Mol Psychiat, Dept Psychiat & Behav Sci, Baltimore, MD 21287 USA. [Sawa, Akira] Johns Hopkins Univ, Sch Med, McKusick Nathans Inst Genet Med, Baltimore, MD 21287 USA. [Ladenheim, Bruce; Krasnova, Irina N.; Cadet, Jean Lud] Natl Inst Drug Abuse, Mol Neuropsychiat Branch, NIH, US Dept HHS, Baltimore, MD USA. [Vogel, Michael W.] Univ Maryland, Maryland Psychiat Res Ctr, Baltimore, MD 21201 USA. RP Pletnikov, MV (reprint author), Johns Hopkins Univ, Sch Med, Dept Psychiat & Behav Sci, Div Neurobiol, 600 N Wolfe St,CMSC 8-121, Baltimore, MD 21287 USA. EM mpletnik@jhmi.edu RI Nomura, Jun/C-2411-2011; Ross, Christopher/H-8395-2013; kamiya, atsushi/L-8550-2016; OI Vogel, Michael/0000-0002-8402-1495; Nomura, Jun/0000-0003-0817-2643 FU National Institute of Mental Health; Autism Speaks; National Alliance for Research on Schizophrenia and Depression; Mortimer W. Sackler Foundation; Cell Science Research Foundation Japan; National Institutes of Health/National Institute on Drug Abuse FX The study was supported by National Institute of Mental Health, Autism Speaks, National Alliance for Research on Schizophrenia and Depression, and the Mortimer W. Sackler Foundation (MVP); The Cell Science Research Foundation Japan (JN); and by National Institutes of Health/National Institute on Drug Abuse-Intramural Research Program (BL, INK, JLC). NR 82 TC 111 Z9 114 U1 3 U2 9 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD DEC 15 PY 2010 VL 68 IS 12 BP 1172 EP 1181 DI 10.1016/j.biopsych.2010.09.022 PG 10 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 695QZ UT WOS:000285389000015 PM 21130225 ER PT J AU Metaferia, BB Rittler, M Gheeya, JS Lee, A Hempel, H Plaza, A Stetler-Stevenson, WG Bewley, CA Khan, J AF Metaferia, Belhu B. Rittler, Matthew Gheeya, Jinesh S. Lee, Albert Hempel, Heidi Plaza, Alberto Stetler-Stevenson, William G. Bewley, Carole A. Khan, Javed TI Synthesis of novel cyclic NGR/RGD peptide analogs via on resin click chemistry SO BIOORGANIC & MEDICINAL CHEMISTRY LETTERS LA English DT Article DE Click chemistry; Aminopeptidase N; Cyclic peptides; Targeted delivery; Fluorescence polarization ID TUMOR VASCULATURE; AMINOPEPTIDASE N; PHAGE DISPLAY; CYCLOADDITION; THERAPEUTICS; ANGIOGENESIS; CYCLIZATION; INTEGRINS; DELIVERY; LIGANDS AB Targeted drug deliveries as well as high resolution imaging of cancerous tissues and organs via specific cancer cell markers have become important in chemotherapeutic interventions of cancer treatment. Short peptides such as RGD and NGR are showing promising results for targeted drug delivery and in vivo imaging. We have applied on resin Huisgen's 1,3-dipolar cycloaddition to synthesize new cyclic RGD and NGR peptide analogs. Preliminary binding assays of these new analogs by fluorescence polarization indicates specific binding to purified CD13 (Aminopeptidase N) and cell lysates from MCF-7 and SKOV-3 cancer cell lines. Published by Elsevier Ltd. C1 [Metaferia, Belhu B.; Gheeya, Jinesh S.; Lee, Albert; Hempel, Heidi; Khan, Javed] NCI, Pediat Oncol Branch, NIH, Bethesda, MD 20892 USA. [Rittler, Matthew; Stetler-Stevenson, William G.] NCI, Radiat Oncol Branch, NIH, Bethesda, MD 20892 USA. [Plaza, Alberto; Bewley, Carole A.] NIDDK, Bioorgan Chem Lab, NIH, Bethesda, MD 20892 USA. RP Khan, J (reprint author), NCI, Pediat Oncol Branch, NIH, Bethesda, MD 20892 USA. EM khanjav@mail.nih.gov RI Stetler-Stevenson, William/H-6956-2012; Khan, Javed/P-9157-2014; OI Stetler-Stevenson, William/0000-0002-5500-5808; Khan, Javed/0000-0002-5858-0488; Gheeya, Jinesh/0000-0002-5246-6262 FU Center for Cancer Research, National Cancer Institute; National Institute of Diabetes and Digestive and Kidney Diseases FX We thank Dr. John Lloyd and Mr. Noel Whittaker from NIDDK/LBC for their assistance with mass spectrometry analysis. We thank Ms. Jessica L. Keffer for her assistance in the NMR experiments and analysis. This work was supported by Intramural Research Programs, Center for Cancer Research, National Cancer Institute (J.K.) and National Institute of Diabetes and Digestive and Kidney Diseases (C.A.B.). NR 23 TC 13 Z9 14 U1 1 U2 28 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0960-894X J9 BIOORG MED CHEM LETT JI Bioorg. Med. Chem. Lett. PD DEC 15 PY 2010 VL 20 IS 24 BP 7337 EP 7340 DI 10.1016/j.bmcl.2010.10.064 PG 4 WC Chemistry, Medicinal; Chemistry, Organic SC Pharmacology & Pharmacy; Chemistry GA 681QW UT WOS:000284332900032 PM 21050757 ER PT J AU Figg, WD Figg, WD AF Figg, William D., II Figg, William D., Sr. TI Cabazitaxel Filling one of the gaps in the treatment of prostate cancer SO CANCER BIOLOGY & THERAPY LA English DT Editorial Material DE taxane; chemotherapy; metastatic cancer; prostate cancer; cabazitaxel; castrate resistant; survival; FDA approval ID MITOXANTRONE PLUS PREDNISONE; PHASE-II TRIAL; EVERY 3 WEEKS; DOCETAXEL; CHEMOTHERAPY; THALIDOMIDE; TAXANE C1 [Figg, William D., II; Figg, William D., Sr.] NCI, NIH, Bethesda, MD 20892 USA. RP Figg, WD (reprint author), NCI, NIH, Bethesda, MD 20892 USA. EM wdfigg@helix.nih.gov; wdfigg@helix.nih.gov RI Figg Sr, William/M-2411-2016 NR 15 TC 4 Z9 5 U1 0 U2 2 PU LANDES BIOSCIENCE PI AUSTIN PA 1806 RIO GRANDE ST, AUSTIN, TX 78702 USA SN 1538-4047 J9 CANCER BIOL THER JI Cancer Biol. Ther. PD DEC 15 PY 2010 VL 10 IS 12 BP 1233 EP 1234 DI 10.4161/cbt.10.12.14085 PG 2 WC Oncology SC Oncology GA 695QT UT WOS:000285388400004 PM 21107022 ER PT J AU Matsumoto, S Yasui, H Mitchell, JB Krishna, MC AF Matsumoto, Shingo Yasui, Hironobu Mitchell, James B. Krishna, Murali C. TI Imaging Cycling Tumor Hypoxia SO CANCER RESEARCH LA English DT Review ID INTERMITTENT HYPOXIA; TRANSIENT HYPOXIA; FREE-RADICALS; OXYGENATION; CANCER; CELLS; HIF-1; RADIOSENSITIVITY; REOXYGENATION; ANGIOGENESIS AB Cycling hypoxia is now a well-recognized phenomenon in animal and human solid tumors. Cycling hypoxia can exist more than 100-mu m distances from a microvessel, and some of these regions have been shown to exist adjacent to normal tissue. Fluctuations in pO(2) of approximately 20 mm Hg can occur with periodicities of minutes to hours and even days. These fluctuations have been attributed to changes in erythrocyte flux, perfusion, and also development of newer vascular networks. Cycling hypoxia has been shown to induce the expression of hypoxia-inducible transcription factor-1 alpha (HIF-1 alpha) and also confer tumor cells and tumor vascular endothelial cells with enhanced prosurvival pathways, making tumors less responsive to radiation and chemotherapy. Imaging of cycling hypoxia in tumors can provide capabilities to help plan appropriate treatment, by taking into account the magnitude and frequency of fluctuations and also their locations adjacent to normal tissue. Electron paramagnetic resonance imaging (EPRI) provides the ability to distinguish chronic and cycling hypoxic regions and has the required spatial and temporal resolutions to provide quantitative maps of tumor pO(2). EPRI can serve as a valuable tool in examining tumor pO(2) longitudinally in response to treatment and in an experimentally chosen time window to spatially map fluctuations in pO(2) noninvasively in animal models of implanted or orthotopic tumors, with a potential for human applications. Cancer Res; 70(24); 10019-23. (C) 2010 AACR. C1 [Krishna, Murali C.] NCI, Radiat Biol Branch, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. RP Krishna, MC (reprint author), NCI, Radiat Biol Branch, Ctr Canc Res, NIH, Bldg 10,Room B3B69,9000 Rockville Pike, Bethesda, MD 20892 USA. EM murali@helix.nih.gov RI Yasui, Hironobu/E-3794-2010 FU Intramural NIH HHS [Z01 BC010476-05] NR 27 TC 57 Z9 60 U1 1 U2 15 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 J9 CANCER RES JI Cancer Res. PD DEC 15 PY 2010 VL 70 IS 24 BP 10019 EP 10023 DI 10.1158/0008-5472.CAN-10-2821 PG 5 WC Oncology SC Oncology GA 694XD UT WOS:000285334200001 PM 21159626 ER PT J AU Aloia, AL Sfanos, KS Isaacs, WB Zheng, QZ Maldarelli, F De Marzo, AM Rein, A AF Aloia, Amanda L. Sfanos, Karen S. Isaacs, William B. Zheng, Qizhi Maldarelli, Frank De Marzo, Angelo M. Rein, Alan TI XMRV: A New Virus in Prostate Cancer? SO CANCER RESEARCH LA English DT Article ID CHRONIC-FATIGUE-SYNDROME; SIMIAN IMMUNODEFICIENCY VIRUS; HUMAN RETROVIRUS XMRV; INFECTIOUS RETROVIRUS; GENE-THERAPY; SEQUENCES; MULTIPLE; DISEASE; TUMORS; BLOOD AB Several recent articles have reported the presence of a gammaretrovirus, termed "XMRV" (xenotropic murine leukemia virus-related virus) in prostate cancers (PCa). If confirmed, this could have enormous implications for the detection, prevention, and treatment of PCa. However, other articles report failure to detect XMRV in PCa. We tested nearly 800 PCa samples, using a combination of real-time PCR and immunohistochemistry (IHC). The PCR reactions were simultaneously monitored for amplification of a single-copy human gene, to confirm the quality of the sample DNA and its suitability for PCR. Controls showed that the PCR assay could detect the XMRV in a single infected cell, even in the presence of a 10,000-fold excess of uninfected human cells. The IHC used 2 rabbit polyclonal antisera, each prepared against a purified murine leukemia virus (MLV) protein. Both antisera always stained XMRV-infected or -transfected cells, but never stained control cells. No evidence for XMRV in PCa was obtained in these experiments. We discuss possible explanations for the discrepancies in the results from different laboratories. It is possible that XMRV is not actually circulating in the human population; even if it is, the data do not seem to support a causal role for this virus in PCa. Cancer Res; 70(24); 10028-33. (C) 2010 AACR. C1 [Aloia, Amanda L.; Maldarelli, Frank; Rein, Alan] NCI, HIV Drug Resistance Program, Frederick, MD 21702 USA. [Sfanos, Karen S.; Zheng, Qizhi; De Marzo, Angelo M.] Brady Urol Res Inst, Dept Pathol, Baltimore, MD USA. [Isaacs, William B.; De Marzo, Angelo M.] Brady Urol Res Inst, Dept Urol, Baltimore, MD USA. [Isaacs, William B.; De Marzo, Angelo M.] Brady Urol Res Inst, Dept Oncol, Baltimore, MD USA. [Isaacs, William B.; Zheng, Qizhi; De Marzo, Angelo M.] Sidney Kimmel Comprehens Canc Ctr, Baltimore, MD USA. RP Rein, A (reprint author), NCI, HIV Drug Resistance Program, Frederick, MD 21702 USA. EM ademarz@jhmi.edu; reina@mail.nih.gov FU NCI-SPORE [P50CA58236]; Prevent Cancer Foundation; NIH, National Cancer Institute, Center for Cancer Research FX IHC studies and a number of the frozen prostate tissues for PCR assays were supported by NCI-SPORE in prostate PCa P50CA58236. K.S. Sfanos is supported by a postdoctoral fellowship award from the Prevent Cancer Foundation. This research was supported in part by the Intramural Research Program of the NIH, National Cancer Institute, Center for Cancer Research. NR 24 TC 52 Z9 52 U1 0 U2 3 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 J9 CANCER RES JI Cancer Res. PD DEC 15 PY 2010 VL 70 IS 24 BP 10028 EP 10033 DI 10.1158/0008-5472.CAN-10-2837 PG 6 WC Oncology SC Oncology GA 694XD UT WOS:000285334200003 PM 20966126 ER PT J AU Roessler, S Jia, HL Budhu, A Forgues, M Ye, QH Lee, JS Thorgeirsson, SS Sun, ZT Tang, ZY Qin, LX Wang, XW AF Roessler, Stephanie Jia, Hu-Liang Budhu, Anuradha Forgues, Marshonna Ye, Qing-Hai Lee, Ju-Seog Thorgeirsson, Snorri S. Sun, Zhongtang Tang, Zhao-You Qin, Lun-Xiu Wang, Xin Wei TI A Unique Metastasis Gene Signature Enables Prediction of Tumor Relapse in Early-Stage Hepatocellular Carcinoma Patients SO CANCER RESEARCH LA English DT Article ID BREAST-CANCER; INTRAHEPATIC RECURRENCE; PROSTATE-CANCER; RISK-FACTORS; EXPRESSION; RESECTION; SURVIVAL; CLASSIFICATION; MANAGEMENT; PROGNOSIS AB Metastasis-related recurrence often occurs in hepatocellular carcinoma (HCC) patients who receive curative therapies. At present, it is challenging to identify patients with high risk of recurrence, which would warrant additional therapies. In this study, we sought to analyze a recently developed metastasis-related gene signature for its utility in predicting HCC survival, using 2 independent cohorts consisting of a total of 386 patients who received radical resection. Cohort 1 contained 247 predominantly HBV-positive cases analyzed with an Affymetrix platform, whereas cohort 2 contained 139 cases with mixed etiology analyzed with the NCI Oligo Set microarray platform. We employed a survival risk prediction algorithm with training, test, and independent cross-validation strategies and found that the gene signature is predictive of overall and disease-free survival. Importantly, risk was significantly predicted independently of clinical characteristics and microarray platform. In addition, survival prediction was successful in patients with early disease, such as small (<5cm in diameter) and solitary tumors, and the signature predicted particularly well for early recurrence risk (<2 years), especially when combined with serum alpha fetoprotein or tumor staging. In conclusion, we have shown in 2 independent cohorts with mixed etiologies and ethnicity that the metastasis gene signature is a useful tool to predict HCC outcome, suggesting the general utility of this classifier. We recommend the use of this classifier as a molecular diagnostic test to assess the risk that an HCC patient will develop tumor relapse within 2 years after surgical resection, particularly for those with early-stage tumors and solitary presentation. Cancer Res; 70(24); 10202-12. (C) 2010 AACR. C1 [Roessler, Stephanie; Budhu, Anuradha; Forgues, Marshonna; Wang, Xin Wei] NCI, Human Carcinogenesis Lab, NIH, Bethesda, MD 20892 USA. [Jia, Hu-Liang; Ye, Qing-Hai; Tang, Zhao-You; Qin, Lun-Xiu] Fudan Univ, Liver Canc Inst, Shanghai 200032, Peoples R China. [Jia, Hu-Liang; Ye, Qing-Hai; Tang, Zhao-You; Qin, Lun-Xiu] Fudan Univ, Zhongshan Hosp, Shanghai 200032, Peoples R China. [Lee, Ju-Seog; Thorgeirsson, Snorri S.] NCI, Expt Carcinogenesis Lab, NIH, Bethesda, MD 20892 USA. [Sun, Zhongtang] Chinese Acad Med Sci, Inst Canc, Natl Lab Mol Oncol, Beijing 100021, Peoples R China. RP Wang, XW (reprint author), NCI, Human Carcinogenesis Lab, NIH, 37 Convent Dr,Bldg 37,Room 3044A, Bethesda, MD 20892 USA. EM qin.lunxiu@zs-hospital.sh.cn; xw3u@nih.gov RI Wang, Xin/B-6162-2009 FU Center for Cancer Research; China National Key Projects for Infectious Disease [2008ZX10002-021]; State Key Basic Research Program of China [2009CB521701]; U.S. National Cancer Institute [Z01-BC 010313, Z01-BC 010876] FX This work was supported by the intramural Research Program of the Center for Cancer Research, the U.S. National Cancer Institute (Z01-BC 010313 and Z01-BC 010876), and by China National Key Projects for Infectious Disease (2008ZX10002-021) and the State Key Basic Research Program of China (2009CB521701). NR 44 TC 171 Z9 175 U1 2 U2 4 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 J9 CANCER RES JI Cancer Res. PD DEC 15 PY 2010 VL 70 IS 24 BP 10202 EP 10212 DI 10.1158/0008-5472.CAN-10-2607 PG 11 WC Oncology SC Oncology GA 694XD UT WOS:000285334200022 PM 21159642 ER PT J AU Liu, M Sakamaki, T Casimiro, MC Willmarth, NE Quong, AA Ju, XM Ojeifo, J Jiao, XM Yeow, WS Katiyar, S Shirley, LA Joyce, D Lisanti, MP Albanese, C Pestell, RG AF Liu, Manran Sakamaki, Toshiyuki Casimiro, Mathew C. Willmarth, Nicole E. Quong, Andrew A. Ju, Xiaoming Ojeifo, John Jiao, Xuanmao Yeow, Wen-Shuz Katiyar, Sanjay Shirley, L. Andrew Joyce, David Lisanti, Michael P. Albanese, Christopher Pestell, Richard G. TI The Canonical NF-kappa B Pathway Governs Mammary Tumorigenesis in Transgenic Mice and Tumor Stem Cell Expansion SO CANCER RESEARCH LA English DT Article ID BREAST-CANCER CELLS; CYCLIN D1; IKK-ALPHA; INDUCIBLE EXPRESSION; SIGNALING PATHWAY; INITIATING CELLS; IN-VIVO; MACROPHAGES; GROWTH; GLAND AB The role of mammary epithelial cell (MEC) NF-kappa B in tumor progression in vivo is unknown, as murine NF-kappa B components and kinases either are required for murine survival or interfere with normal mammary gland development. As NF-kappa B inhibitors block both tumor-associated macrophages (TAM) and MEC NF-kappa B, the importance of MEC NF-kappa B to tumor progression in vivo remained to be determined. Herein, an MEC-targeted inducible transgenic inhibitor of NF-kappa B (I kappa B alpha SR) was developed in ErbB2 mammary oncomice. Inducible suppression of NF-kappa B in the adult mammary epithelium delayed the onset and number of new tumors. Within similar sized breast tumors, TAM and tumor neoangiogenesis was reduced. Coculture experiments demonstrated MEC NF-kappa B enhanced TAM recruitment. Genome-wide expression and proteomic analysis showed that IkBaSR inhibited tumor stem cell pathways. IkBaSR inhibited breast tumor stem cell markers in transgenic tumors, reduced stem cell expansion in vitro, and repressed expression of Nanog and Sox2 in vivo and in vitro. MEC NF-kappa B contributes to mammary tumorigenesis. As we show that NF-kappa B contributes to expansion of breast tumor stem cells and heterotypic signals that enhance TAM and vasculogenesis, these processes may contribute to NF-kappa B-dependent mammary tumorigenesis. Cancer Res; 70(24); 10464-73. (C)2010 AACR. C1 [Liu, Manran; Casimiro, Mathew C.; Willmarth, Nicole E.; Quong, Andrew A.; Ju, Xiaoming; Jiao, Xuanmao; Yeow, Wen-Shuz; Katiyar, Sanjay; Lisanti, Michael P.; Pestell, Richard G.] Thomas Jefferson Univ, Kimmel Canc Ctr, Dept Canc Biol, Philadelphia, PA 19107 USA. [Shirley, L. Andrew] Thomas Jefferson Univ, Kimmel Canc Ctr, Dept Surg, Philadelphia, PA 19107 USA. [Liu, Manran] Chongqing Med Univ, Minist Educ, Key Lab Clin Lab Diagnost, Chongqing, Peoples R China. [Sakamaki, Toshiyuki] Niigata Univ Pharm & Appl Life Sci, Niigata, Japan. [Ojeifo, John] NCI, Ctr Reduce Canc Hlth Disparities, Rockville, MD USA. [Joyce, David] Univ Western Australia, Sch Med & Pharmacol, Perth, WA 6009, Australia. [Albanese, Christopher] Georgetown Univ, Lombardi Comprehens Canc Ctr, Washington, DC USA. RP Pestell, RG (reprint author), Thomas Jefferson Univ, Kimmel Canc Ctr, Dept Canc Biol, 233 S 10th St, Philadelphia, PA 19107 USA. EM Richard.Pestell@jefferson.edu RI Lisanti, Michael/C-6866-2013 FU NIH [P30CA56036]; Dr. Ralph and Marian C. Falk Medical Research Trust; Pennsylvania Department of Health; [R01CA70896]; [R01CA75503]; [R01CA107382]; [R01CA86072]; [R01CA120876] FX This work was supported in part by R01CA70896, R01CA75503, R01CA107382, R01CA86072 (R.G.P.), and R01CA120876 (M.P.L). The Kimmel Cancer Center was supported by the NIH Cancer Center Core grant P30CA56036 (R.G.P.). This project is funded in part from the Dr. Ralph and Marian C. Falk Medical Research Trust and a grant from Pennsylvania Department of Health (R.G.P.). NR 42 TC 83 Z9 92 U1 1 U2 6 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 J9 CANCER RES JI Cancer Res. PD DEC 15 PY 2010 VL 70 IS 24 BP 10464 EP 10473 DI 10.1158/0008-5472.CAN-10-0732 PG 10 WC Oncology SC Oncology GA 694XD UT WOS:000285334200047 PM 21159656 ER PT J AU Bao, Y Chen, JQ Wu, Y Leng, XH Wang, E Marincola, F Radvanyi, LG AF Bao, Y. Chen, J. Q. Wu, Y. Leng, X-H Wang, E. Marincola, F. Radvanyi, L. G. TI TRPS-1, a New GATA Family Transcription Factor, Regulates Epithelial-Mesenchymal Transition and Maintains an Estrogen Responsive, Claudin-Positive Phenotype in Breast Cancer Cells SO CANCER RESEARCH LA English DT Meeting Abstract C1 Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA. 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 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD DEC 15 PY 2010 VL 70 SU 24 MA P6-08-14 DI 10.1158/0008-5472.SABCS10-P6-08-14 PG 1 WC Oncology SC Oncology GA V43QL UT WOS:000209695800264 ER PT J AU Bode, AM Li, J Cho, YY Ericson, ME Lubet, RA Grubbs, C AF Bode, A. M. Li, J. Cho, Y. Y. Ericson, M. E. Lubet, R. A. Grubbs, C. TI Tumors Resistant to Iressa Treatment Show Increased Aberrant Expression of CREB (Ser133) SO CANCER RESEARCH LA English DT Meeting Abstract C1 Univ Minnesota, Austin, MN USA. Univ Minnesota, Minneapolis, MN USA. NCI, Rockville, MD USA. Univ Alabama Birmingham, Birmingham, AL USA. RI ericson, marna/C-9591-2017 OI ericson, marna/0000-0003-1862-4957 NR 0 TC 0 Z9 0 U1 0 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 DEC 15 PY 2010 VL 70 SU 24 MA P2-07-03 DI 10.1158/0008-5472.SABCS10-P2-07-03 PG 1 WC Oncology SC Oncology GA V43QL UT WOS:000209695801071 ER PT J AU Eng-Wong, J Venzon, D Cohen, P Isaacs, C Warren, R Wedam, S Zujewski, JA Korde, L Byrne, C AF Eng-Wong, J. Venzon, D. Cohen, P. Isaacs, C. Warren, R. Wedam, S. Zujewski, J. A. Korde, L. Byrne, C. TI Effect of Exemestane on Mammographic Density in Postmenopausal Women at Risk for Breast Cancer SO CANCER RESEARCH LA English DT Meeting Abstract C1 Georgetown Univ, Washington, DC USA. 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 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD DEC 15 PY 2010 VL 70 SU 24 MA P1-07-03 DI 10.1158/0008-5472.SABCS10-P1-07-03 PG 1 WC Oncology SC Oncology GA V43QL UT WOS:000209695800439 ER PT J AU Gee, AM Pfalzer, L Stout, N Levy, E McGarvey, C Springer, B Soballe, P Gerber, L AF Gee, A. Morehead Pfalzer, L. Stout, N. Levy, E. McGarvey, C. Springer, B. Soballe, P. Gerber, L. TI Racial Disparities in Physical and Functional Domains in Women with Early Breast Cancer SO CANCER RESEARCH LA English DT Meeting Abstract C1 NIH, Bethesda, MD 20892 USA. Univ Michigan, Flint, MI 48503 USA. Natl Naval Med Ctr, Bethesda, MD USA. CLM Consulting, Rockville, MD USA. Balboa Naval Hosp, San Diego, CA USA. George Mason Univ, Fairfax, VA 22030 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 DEC 15 PY 2010 VL 70 SU 24 MA P1-10-06 DI 10.1158/0008-5472.SABCS10-P1-10-06 PG 1 WC Oncology SC Oncology GA V43QL UT WOS:000209695800458 ER PT J AU Gomez, J AF Gomez, J. TI Molecular Profiling of Stage II and Ill Breast Cancer in Latin American Women Receiving Standard-of-Care Treatment SO CANCER RESEARCH LA English DT Meeting Abstract C1 [Gomez, J.] NCI, NIH, OD, 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 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD DEC 15 PY 2010 VL 70 SU 24 MA P6-04-16 DI 10.1158/0008-5472.SABCS10-P6-04-16 PG 1 WC Oncology SC Oncology GA V43QL UT WOS:000209695800237 ER PT J AU Heckman-Stoddard, BM Grubbs, CJ Johnson, K Lubet, RA AF Heckman-Stoddard, B. M. Grubbs, C. J. Johnson, K. Lubet, R. A. TI Doses of Selective Estrogen Receptor Modulations (SERMS) Required for Prevention and Therapy of Chemically-Induced Mammary Cancers SO CANCER RESEARCH LA English DT Meeting Abstract C1 NCI, Bethesda, MD 20892 USA. Univ Alabama Birmingham, Birmingham, AL 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 DEC 15 PY 2010 VL 70 SU 24 MA P1-08-04 DI 10.1158/0008-5472.SABCS10-P1-08-04 PG 1 WC Oncology SC Oncology GA V43QL UT WOS:000209695800443 ER PT J AU Ingle, JN Liu, M Wickerham, DL Schaid, DJ Mushiroda, T Kubo, M Costantino, JP Goetz, MP Ames, MM Wang, L Vogel, VG Paik, S Batzler, A Flockhart, DA Wolmark, N Nakamura, Y Weinshilboum, R AF Ingle, J. N. Liu, M. Wickerham, D. L. Schaid, D. J. Mushiroda, T. Kubo, M. Costantino, J. P. Goetz, M. P. Ames, M. M. Wang, L. Vogel, V. G. Paik, S. Batzler, A. Flockhart, D. A. Wolmark, N. Nakamura, Y. Weinshilboum, R. TI Genome-Wide Associations of Breast Events and Functional Genomic Studies in High-Risk Women Receiving Tamoxifen or Raloxifene on NSABP P1 and P2 Prevention Trials. A Pharmacogenomics Research Network-RIKEN-NSABP Collaboration SO CANCER RESEARCH LA English DT Meeting Abstract C1 Mayo Clin, Rochester, MN USA. NSABP, Pittsburgh, PA USA. RIKEN, Tokyo, Japan. Indiana Univ, Indianapolis, IN 46204 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 DEC 15 PY 2010 VL 70 SU 24 MA PD05-02 DI 10.1158/0008-5472.SABCS10-PD05-02 PG 2 WC Oncology SC Oncology GA V43QL UT WOS:000209695801408 ER PT J AU Lee, MP Kadota, M Yang, HH Clifford, RJ Dunn, BK AF Lee, M. P. Kadota, M. Yang, H. H. Clifford, R. J. Dunn, B. K. TI Novel Genome-Wide DNA Methylation Signatures of Primary Breast Tumor Subtypes SO CANCER RESEARCH LA English DT Meeting Abstract C1 [Lee, M. P.; Kadota, M.; Yang, H. H.; Clifford, R. J.; Dunn, B. K.] 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 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD DEC 15 PY 2010 VL 70 SU 24 MA P3-04-04 DI 10.1158/0008-5472.SABCS10-P3-04-04 PG 1 WC Oncology SC Oncology GA V43QL UT WOS:000209695801193 ER PT J AU Lubet, RA Iwata, K Szabo, E Grubbs, CJ AF Lubet, R. A. Iwata, K. Szabo, E. Grubbs, C. J. TI Alternative Dosing Regimens with Tarceva in a Mammary Cancer Model: Effects on Efficacy and Potential Effects on Toxicity SO CANCER RESEARCH LA English DT Meeting Abstract C1 NCI, Bethesda, MD 20892 USA. OSI Pharmaceut, Farmingdale, NY USA. Univ Alabama Birmingham, Birmingham, AL 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 DEC 15 PY 2010 VL 70 SU 24 MA P1-08-03 DI 10.1158/0008-5472.SABCS10-P1-08-03 PG 1 WC Oncology SC Oncology GA V43QL UT WOS:000209695800442 ER PT J AU McShane, LM AF McShane, L. M. TI Statistical Challenges in Predictive and Prognostic Biomarker Studies: How To Avoid Wasting Your Time and Specimens SO CANCER RESEARCH LA English DT Meeting Abstract C1 [McShane, L. M.] 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 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD DEC 15 PY 2010 VL 70 SU 24 MA ES4-1 DI 10.1158/0008-5472.SABCS10-ES4-1 PG 1 WC Oncology SC Oncology GA V43QL UT WOS:000209695800362 ER PT J AU Nyante, SJ Faupel-Badger, JM Sherman, ME Gaudet, MM Falk, RT Andaya, AA Pfeiffer, RM Lissowska, J Brinton, LA Peplonska, B Vonderhaar, BK Chanock, SJ Garcia-Closas, M Figueroa, JD AF Nyante, S. J. Faupel-Badger, J. M. Sherman, M. E. Gaudet, M. M. Falk, R. T. Andaya, A. A. Pfeiffer, R. M. Lissowska, J. Brinton, L. A. Peplonska, B. Vonderhaar, B. K. Chanock, S. J. Garcia-Closas, M. Figueroa, J. D. TI Genetic Variation in Prolactin and Prolactin Receptor, and Relationships with Serum Prolactin Levels and Breast Cancer Risk SO CANCER RESEARCH LA English DT Meeting Abstract C1 NCI, Bethesda, MD 20892 USA. Albert Einstein Coll Med, New York, NY USA. Ctr Canc, Warsaw, Poland. M Sklodowska Curie Inst Oncol, Warsaw, Poland. Nofer Inst Occupat Med, Lodz, Poland. 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 DEC 15 PY 2010 VL 70 SU 24 MA P3-12-05 DI 10.1158/0008-5472.SABCS10-P3-12-05 PG 1 WC Oncology SC Oncology GA V43QL UT WOS:000209695801274 ER PT J AU Sgroi, DC Finkelstein, DM Shepherd, L Ingle, JN Rimm, DL Sasano, H Porter, P Pins, M Paik, S Ristimaki, A Pritchard, KI Tu, D Goss, PE AF Sgroi, D. C. Finkelstein, D. M. Shepherd, L. Ingle, J. N. Rimm, D. L. Sasano, H. Porter, P. Pins, M. Paik, S. Ristimaki, A. Pritchard, K. I. Tu, D. Goss, P. E. TI Quantitative Protein and Gene Expression Biomarkers of Tamoxifen and Letrozole Recurrence in the NCIC CTG MA.17 Cohort SO CANCER RESEARCH LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. Queens Univ, Kingston, ON, Canada. Mayo Clin, Rochester, MN USA. Yale Univ, Sch Med, New Haven, CT USA. Tohoku Univ, Sch Med, Sendai, Miyagi 980, Japan. Univ Washington Med, Seattle, WA USA. Advocate Lutheran Gen Hosp, Park Ridge, IL USA. Natl Surg Adjuvant Breast & Bowel Project, Pittsburgh, PA USA. Univ Helsinki, FIN-00014 Helsinki, Finland. Sunnybrook Hlth Sci Ctr, Toronto, ON M4N 3M5, Canada. 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 DEC 15 PY 2010 VL 70 SU 24 MA P3-10-26 DI 10.1158/0008-5472.SABCS10-P3-10-26 PG 1 WC Oncology SC Oncology GA V43QL UT WOS:000209695801237 ER PT J AU Simone, NL Dan, TD Smith, SL Shih, JH Lita, E Sciuto, L Danforth, D Camphausen, K AF Simone, N. L. Dan, T. D. Smith, S. L. Shih, J. H. Lita, E. Sciuto, L. Danforth, D. Camphausen, K. TI Twenty-Five Year Results in the Treatment of Early Breast Carcinoma with Mastectomy Versus Breast Conservation Therapy: The National Cancer Institute Randomized Trial SO CANCER RESEARCH LA English DT Meeting Abstract C1 NCI, NIH, Bethesda, MD 20892 USA. 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 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD DEC 15 PY 2010 VL 70 SU 24 MA P4-10-01 DI 10.1158/0008-5472.SABCS10-P4-10-01 PG 1 WC Oncology SC Oncology GA V43QL UT WOS:000209695800109 ER PT J AU Tang, G Costantino, JP Crager, M Shak, S Wolmark, N AF Tang, G. Costantino, J. P. Crager, M. Shak, S. Wolmark, N. TI Comparing the Prediction of Chemotherapy Benefit in Patients with Node-Negative, ER-Positive Breast Cancer Using the Recurrence Score and a New Measure That Integrates Clinical and Pathologic Factors with the Recurrence Score SO CANCER RESEARCH LA English DT Meeting Abstract C1 NSABP, Pittsburgh, PA USA. Genom Hlth Inc, Redwood City, CA 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 DEC 15 PY 2010 VL 70 SU 24 MA S4-9 DI 10.1158/0008-5472.SABCS10-S4-9 PG 2 WC Oncology SC Oncology GA V43QL UT WOS:000209695802018 ER PT J AU Zielinski, R Lyakhov, I Hassan, M Kuban, M Shafer-Weaver, K Capala, J AF Zielinski, R. Lyakhov, I. Hassan, M. Kuban, M. Shafer-Weaver, K. Capala, J. TI Affitoxin - A Potent Therapeutic Agent for Treatment of HER2-Overexpressing Tumors SO CANCER RESEARCH LA English DT Meeting Abstract C1 NCI, NIH, Bethesda, MD 20892 USA. SAIC Frederick Inc, NCI Frederick, Frederick, MD USA. Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, NIH, Bethesda, MD 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 DEC 15 PY 2010 VL 70 SU 24 MA P3-14-23 DI 10.1158/0008-5472.SABCS10-P3-14-23 PG 1 WC Oncology SC Oncology GA V43QL UT WOS:000209695801312 ER PT J AU Wu, JJ Quijano, C Wang, JM Finkel, T AF Wu, J. Julie Quijano, Celia Wang, Jiamei Finkel, Toren TI Metabolism meets autophagy SO CELL CYCLE LA English DT Editorial Material ID BETA-CELL MASS; STRESS C1 [Wu, J. Julie; Quijano, Celia; Wang, Jiamei; Finkel, Toren] NHLBI, Ctr Mol Med, NIH, Bethesda, MD 20892 USA. RP Finkel, T (reprint author), NHLBI, Ctr Mol Med, NIH, Bldg 10, Bethesda, MD 20892 USA. EM finkelt@nih.gov NR 9 TC 5 Z9 5 U1 0 U2 1 PU LANDES BIOSCIENCE PI AUSTIN PA 1806 RIO GRANDE ST, AUSTIN, TX 78702 USA SN 1538-4101 J9 CELL CYCLE JI Cell Cycle PD DEC 15 PY 2010 VL 9 IS 24 BP 4780 EP 4781 DI 10.4161/cc.9.24.14273 PG 2 WC Cell Biology SC Cell Biology GA 695AQ UT WOS:000285343400006 PM 21150322 ER PT J AU Bates, SE AF Bates, Susan E. TI Striving to Improve Outcomes in Oncology: Unmet Expectations in a Complex Disease SO CLINICAL CANCER RESEARCH LA English DT Editorial Material C1 NCI, Bethesda, MD 20892 USA. RP Bates, SE (reprint author), NCI, Bethesda, MD 20892 USA. NR 1 TC 1 Z9 1 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 J9 CLIN CANCER RES JI Clin. Cancer Res. PD DEC 15 PY 2010 VL 16 IS 24 BP 5950 EP 5950 DI 10.1158/1078-0432.CCR-10-2940 PG 1 WC Oncology SC Oncology GA 695YJ UT WOS:000285408600007 PM 21169246 ER PT J AU Yu, P Steel, JC Zhang, ML Morris, JC Waldmann, TA AF Yu, Ping Steel, Jason C. Zhang, Meili Morris, John C. Waldmann, Thomas A. TI Simultaneous Blockade of Multiple Immune System Inhibitory Checkpoints Enhances Antitumor Activity Mediated by Interleukin-15 in a Murine Metastatic Colon Carcinoma Model SO CLINICAL CANCER RESEARCH LA English DT Article ID CD8(+) T-CELLS; CHRONIC VIRAL-INFECTION; NATURAL-KILLER; REGULATORY T; PD-1; IL-15; RECEPTOR; IMMUNOTHERAPY; ACTIVATION; EXPRESSION AB Purpose: Interleukin 15 (IL-15) is a promising cytokine for immunotherapy of cancer due to its ability to stimulate the immunity of natural killer, B, and T cells. Its effectiveness, however, may be limited by inhibitory checkpoints and pathways that can attenuate immune responses. Finding strategies to abrogate these negative regulators and enhance the efficacy of IL-15 is a critical challenge. Experimental Design: In a preclinical study, we evaluated IL-15 combined with antibodies to block the negative immune regulators cytotoxic T-lymphocyte antigen 4 (CTLA-4) and programmed death ligand 1 (PD-L1) in a metastatic murine CT26 colon carcinoma model. Results: IL-15 treatment resulted in a significant prolongation of survival in mice with metastatic tumor. Administration of IL-15, however, also increased expression of PD-1 on the surface of CD8(+) T cells including CD8(+)CD44(high) memory phenotype T cells. Moreover, IL-15 also increased the secretion of the immunosuppressive cytokine, IL-10. Combining IL-15 with anti-PD-L1 and anti-CTLA-4 (multiple immune checkpoint blockade) exhibited greater CTL killing and IFN gamma secretion. Moreover, this combination resulted in a significant reduction in surface expression of PD-1 on CD8(+) T cells, a decrease in IL-10 secretion, and led to significantly longer survival of tumor-bearing animals compared with mice treated with IL-15 alone or combined singularly with anti-PD-L1 or anti-CTLA-4. Conclusions: Combining the immune stimulatory properties of IL-15 with the simultaneous removal of 2 critical immune system inhibitory checkpoints, we showed enhancement of immune responses leading to increased antitumor activity. Clin Cancer Res; 16(24); 6019-28. (C) 2010 AACR. C1 [Yu, Ping; Steel, Jason C.; Zhang, Meili; Morris, John C.; Waldmann, Thomas A.] NCI, Metab Branch, Ctr Canc Res, Bethesda, MD 20892 USA. [Zhang, Meili] NCI, Lab Anim Sci Program, SAIC Frederick Inc, Frederick, MD 21701 USA. RP Waldmann, TA (reprint author), NCI, Metab Branch, Ctr Canc Res, Bldg 10,Room 4N115,10 Ctr Dr, Bethesda, MD 20892 USA. EM tawald@mail.nih.gov RI Steel, Jason/D-1805-2013 OI Steel, Jason/0000-0003-3608-7542 FU NIH, National Cancer Institute, Center for Cancer Research FX This work was supported by the Intramural Research Program of the NIH, National Cancer Institute, Center for Cancer Research. NR 38 TC 75 Z9 76 U1 1 U2 10 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1078-0432 J9 CLIN CANCER RES JI Clin. Cancer Res. PD DEC 15 PY 2010 VL 16 IS 24 BP 6019 EP 6028 DI 10.1158/1078-0432.CCR-10-1966 PG 10 WC Oncology SC Oncology GA 695YJ UT WOS:000285408600017 PM 20924130 ER PT J AU Jamal, M Rath, BH Williams, ES Camphausen, K Tofilon, PJ AF Jamal, Muhammad Rath, Barbara H. Williams, Eli S. Camphausen, Kevin Tofilon, Philip J. TI Microenvironmental Regulation of Glioblastoma Radioresponse SO CLINICAL CANCER RESEARCH LA English DT Article ID TUMOR STEM-CELLS; HISTONE H2AX PHOSPHORYLATION; INITIATING CELLS; STRAND BREAKS; DNA-DAMAGE; X-RAYS; LINES; CANCER; RADIOTHERAPY; RADIOSENSITIVITY AB Purpose: Brain tumor xenografts initiated from human glioblastoma (GBM) stem-like cells (TSC) simulate the biological characteristics of GBMs in situ. Therefore, to determine whether the brain microenvironment affects the intrinsic radiosensitivity of GBM cells, we compared the radioresponse of GBM TSCs grown in vitro and as brain tumor xenografts. Experimental Design: As indicators of DNA double-strand breaks (DSB), gamma H2AX, and 53BP1 foci were defined after irradiation of 2 GBM TSC lines grown in vitro and as orthotopic xenografts in nude mice. Microarray analysis was conducted to compare gene expression patterns under each growth condition. Results: Dispersal of radiation-induced gamma H2AX and 53BP1 foci was faster in the tumor cells grown as orthotopic xenografts compared with cells irradiated in vitro. In addition, cells irradiated in vivo were approximately 3-fold less susceptible to foci induction as compared with cells grown in vitro. Microarray analysis revealed a significant number of genes whose expression was commonly affected in the 2 GBM models by orthotopic growth conditions. Consistent with the decrease in sensitivity to foci induction, genes related to reactive oxygen species (ROS) metabolism were expressed at higher levels in the brain tumor xenografts. Conclusion: gamma H2AX and 53BP1 foci analyses indicate that GBM cells irradiated within orthotopic xenografts have a greater capacity to repair DSBs and are less susceptible to their induction than tumor cells irradiated under in vitro growth conditions. Because DSB induction and repair are critical determinants of radiosensitivity, these results imply that the brain microenvironment contributes to GBM radioresistance. Clin Cancer Res; 16(24); 6049-59. (C) 2010 AACR. C1 [Tofilon, Philip J.] H Lee Moffitt Canc Ctr & Res Inst, Drug Discovery Dept, DRDIS SRB3, Tampa, FL 33612 USA. [Camphausen, Kevin] NCI, Radiat Oncol Branch, Bethesda, MD 20892 USA. RP Tofilon, PJ (reprint author), H Lee Moffitt Canc Ctr & Res Inst, Drug Discovery Dept, DRDIS SRB3, 12902 Magnolia Dr, Tampa, FL 33612 USA. EM philip.tofilon@moffitt.org FU National Institute of Health [CA138519]; National Cancer Institute FX This work was supported by grant CA138519 from the National Institute of Health (P.J.T.) and a Cancer Center Support Grant issued to Moffitt Cancer Center from the National Cancer Institute. NR 36 TC 31 Z9 31 U1 0 U2 2 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1078-0432 J9 CLIN CANCER RES JI Clin. Cancer Res. PD DEC 15 PY 2010 VL 16 IS 24 BP 6049 EP 6059 DI 10.1158/1078-0432.CCR-10-2435 PG 11 WC Oncology SC Oncology GA 695YJ UT WOS:000285408600020 PM 21037023 ER PT J AU Dudley, ME Gross, CA Langhan, MM Garcia, MR Sherry, RM Yang, JC Phan, GQ Kammula, US Hughes, MS Citrin, DE Restifo, NP Wunderlich, JR Prieto, PA Hong, JJ Langan, RC Zlott, DA Morton, KE White, DE Laurencot, CM Rosenberg, SA AF Dudley, Mark E. Gross, Colin A. Langhan, Michelle M. Garcia, Marcos R. Sherry, Richard M. Yang, James C. Phan, Giao Q. Kammula, Udai S. Hughes, Marybeth S. Citrin, Deborah E. Restifo, Nicholas P. Wunderlich, John R. Prieto, Peter A. Hong, Jenny J. Langan, Russell C. Zlott, Daniel A. Morton, Kathleen E. White, Donald E. Laurencot, Carolyn M. Rosenberg, Steven A. TI CD8+ Enriched "Young" Tumor Infiltrating Lymphocytes Can Mediate Regression of Metastatic Melanoma SO CLINICAL CANCER RESEARCH LA English DT Article ID CD8(+) T-CELLS; TRANSFER THERAPY; CD8-T-CELL MEMORY; ADOPTIVE TRANSFER; CD4-T-CELL HELP; CANCER; SURVIVAL; PERSISTENCE; IMMUNOTHERAPY; AUTOIMMUNITY AB Purpose: Tumor-infiltrating lymphocytes (TIL) and interleukin (IL)-2 administered following lymphodepletion can cause the durable complete regression of bulky metastatic melanoma in patients refractory to approved treatments. However, the generation of a unique tumor-reactive TIL culture for each patient may be prohibitively difficult. We therefore investigated the clinical and immunologic impact of unscreened, CD8+ enriched "young" TIL. Experimental Design: Methods were developed for generating TIL that minimized the time in culture and eliminated the individualized tumor-reactivity screening step. Thirty-three patients were treated with these CD8+ enriched young TIL and IL-2 following nonmyeloablative lymphodepletion (NMA). Twenty-three additional patients were treated with CD8+ enriched young TIL and IL-2 after lymphodepletion with NMA and 6 Gy of total body irradiation. Results: Young TIL cultures for therapy were successfully established from 83% of 122 consecutive melanoma patients. Nineteen of 33 patients (58%) treated with CD8+ enriched young TIL and NMA had an objective response (Response Evaluation Criteria in Solid Tumors) including 3 complete responders. Eleven of 23 patients (48%) treated with TIL and 6 Gy total body irradiation had an objective response including 2 complete responders. At 1 month after TIL infusion the absolute CD8+ cell numbers in the periphery were highly correlated with response. Conclusions: This study shows that a rapid and simplified method can be used to reliably generate CD8+ enriched young TIL for administration as an individualized therapy for advanced melanoma, and may allow this potentially effective treatment to be applied at other institutions and to reach additional patients. Clin Cancer Res; 16(24); 6122-31. (C) 2010 AACR. C1 [Dudley, Mark E.; Gross, Colin A.; Langhan, Michelle M.; Garcia, Marcos R.; Sherry, Richard M.; Yang, James C.; Phan, Giao Q.; Kammula, Udai S.; Hughes, Marybeth S.; Restifo, Nicholas P.; Wunderlich, John R.; Prieto, Peter A.; Hong, Jenny J.; Langan, Russell C.; Morton, Kathleen E.; White, Donald E.; Laurencot, Carolyn M.; Rosenberg, Steven A.] NCI, Surg Branch, Bethesda, MD 20892 USA. [Citrin, Deborah E.] NCI, Radiat Oncol Branch, Bethesda, MD 20892 USA. [Zlott, Daniel A.] NIH, Dept Pharm, Clin Res Ctr, Bethesda, MD 20892 USA. RP Dudley, ME (reprint author), NCI, Natl Surg Branch, CRC 3W-5752,10 Ctr Dr, Bethesda, MD 20892 USA. EM med@nih.gov RI Restifo, Nicholas/A-5713-2008; OI Gross, Colin/0000-0002-7061-5073; Restifo, Nicholas P./0000-0003-4229-4580 FU Intramural NIH HHS [Z01 BC011020-01, ZIC BC011020-02] NR 31 TC 130 Z9 133 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 J9 CLIN CANCER RES JI Clin. Cancer Res. PD DEC 15 PY 2010 VL 16 IS 24 BP 6122 EP 6131 DI 10.1158/1078-0432.CCR-10-1297 PG 10 WC Oncology SC Oncology GA 695YJ UT WOS:000285408600027 PM 20668005 ER PT J AU Hassan, R Cohen, SJ Phillips, M Pastan, I Sharon, E Kelly, RJ Schweizer, C Weil, S Laheru, D AF Hassan, Raffit Cohen, Steven J. Phillips, Martin Pastan, Ira Sharon, Elad Kelly, Ronan J. Schweizer, Charles Weil, Susan Laheru, Daniel TI Phase I Clinical Trial of the Chimeric Anti-Mesothelin Monoclonal Antibody MORAb-009 in Patients with Mesothelin-Expressing Cancers SO CLINICAL CANCER RESEARCH LA English DT Article ID PANCREATIC-CANCER; OVARIAN-CANCER; PERITONEAL MESOTHELIOMA; RECOMBINANT IMMUNOTOXIN; DIAGNOSIS; ADENOCARCINOMAS; INFUSION; MARKER; SS1P AB Purpose: MORAb-009 is a chimeric monoclonal antibody that targets mesothelin, a tumor differentiation antigen overexpressed in pancreatic cancer, ovarian cancer, mesothelioma, and other malignancies. We conducted a phase I clinical trial of MORAb-009 in patients with advanced mesothelin-expressing cancers to determine its safety, dose-limiting toxicity (DLT), and maximum tolerated dose (MTD). Methods: Cohorts consisting of 3 to 6 subjects each received MORAb-009 intravenously on days 1, 8, 15, and 22 at progressively increasing doses ranging from 12.5 to 400 mg/m(2). Disease evaluation with computed tomography occurred on day 35. Subjects with responding or stable disease could receive additional cycles of MORAb-009. Results: A total of 24 subjects were treated including 13 mesothelioma, 7 pancreatic cancer, and 4 ovarian cancer patients. The median number of MORAb-009 infusions was 4 (range 1-24 infusions). At the 400 mg/m 2 dose level, 2 subjects experienced DLT (grade 4 transaminitis and a grade 3 serum sickness). Thus, although there were other contributing causes of these adverse events, 200 mg/m(2) was considered the MTD. Other adverse events at least possibly related to MORAb-009 included 7 drug hypersensitivity events (all grade 1 or 2) and a thromboembolic event (grade 4). Eleven subjects had stable disease. There was a dose-dependent increase in serum MORAb-009 concentration. Conclusion: MORAb-009 is well tolerated and the MTD when administered weekly is conservatively set at 200 mg/m(2). In this group of previously treated patients, 11 subjects had stable disease. Phase II studies of MORAb-009 in different mesothelin-expressing cancers are ongoing. Clin Cancer Res; 16(24); 6132-8. (C)2010 AACR. C1 [Hassan, Raffit; Pastan, Ira] NCI, Mol Biol Lab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. [Cohen, Steven J.] Fox Chase Canc Ctr, Dept Med Oncol, Philadelphia, PA 19111 USA. [Phillips, Martin; Schweizer, Charles; Weil, Susan] Morphotek Inc, Exton, PA USA. [Sharon, Elad; Kelly, Ronan J.] NCI, Med Oncol Branch, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. [Laheru, Daniel] Johns Hopkins Sch Med, Dept Med Oncol, Sidney Kimmel Canc Ctr, Baltimore, MD USA. RP Hassan, R (reprint author), NCI, Mol Biol Lab, Ctr Canc Res, NIH, 37 Convent Dr,Rm 5116, Bethesda, MD 20892 USA. EM hassanr@mail.nih.gov FU NIH, National Cancer Institute, Center for Cancer Research; Morphotek, Inc.; National Cancer Institute FX This research was supported in part by the Intramural Research Program of the NIH, National Cancer Institute, Center for Cancer Research, and in part by Morphotek, Inc., under a Cooperative Research and Development Agreement with National Cancer Institute. NR 25 TC 75 Z9 76 U1 1 U2 10 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1078-0432 J9 CLIN CANCER RES JI Clin. Cancer Res. PD DEC 15 PY 2010 VL 16 IS 24 BP 6132 EP 6138 DI 10.1158/1078-0432.CCR-10-2275 PG 7 WC Oncology SC Oncology GA 695YJ UT WOS:000285408600028 PM 21037025 ER PT J AU Libutti, SK Paciotti, GF Byrnes, AA Alexander, HR Gannon, WE Walker, M Seidel, GD Yuldasheva, N Tamarkin, L AF Libutti, Steven K. Paciotti, Giulio F. Byrnes, Adriana A. Alexander, H. Richard, Jr. Gannon, William E. Walker, Melissa Seidel, Geoffrey D. Yuldasheva, Nargiza Tamarkin, Lawrence TI Phase I and Pharmacokinetic Studies of CYT-6091, a Novel PEGylated Colloidal Gold-rhTNF Nanomedicine SO CLINICAL CANCER RESEARCH LA English DT Article ID TUMOR-NECROSIS-FACTOR; ISOLATED LIMB PERFUSION; ADVANCED MALIGNANT DISEASE; SOFT-TISSUE SARCOMA; FACTOR-ALPHA; TNF-ALPHA; INTERFERON-GAMMA; RTNF-ALPHA; MELPHALAN; TRIAL AB Purpose: A novel nanomedicine, CYT-6091, constructed by simultaneously binding recombinant human tumor necrosis factor alpha (rhTNF) and thiolyated polyethylene glycol to the surface of 27-nm colloidal gold particles, was tested in a phase I dose escalation clinical trial in advanced stage cancer patients. Experimental Design: CYT-6091, whose dosing was based on the amount of rhTNF in the nanomedicine, was injected intravenously, and 1 cycle of treatment consisted of 2 treatments administered 14 days apart. Results: Doses from 50 mu g/m(2) to 600 mu g/m(2) were well tolerated, and no maximum tolerated dose (MTD) was reached, as the highest dose exceeded the target dosage of 1-mg rhTNF per treatment, exceeding the previous MTD for native rhTNF by 3-fold. The first 2 patients on the study, each receiving 50 mu g/m(2), did not receive any prophylactic antipyretics or H2 blockade. A predicted, yet controllable fever occurred in these patients, so all subsequently treated patients received prophylactic antipyretics and H2 blockers. However, even at the highest dose rhTNF's dose-limiting toxic effect of hypotension was not seen. Using electron microscopy to visualize nanoparticles of gold in patient biopsies of tumor and healthy tissue showed that patient biopsies taken 24 hours after treatment had nanoparticles of gold in tumor tissue. Conclusions: These data indicate that rhTNF formulated as CYT-6091 may be administered systemically at doses of rhTNF that were previously shown to be toxic and that CYT-6091 may target to tumors. Future clinical studies will focus on combining CYT-6091 with approved chemotherapies for the systemic treatment of nonresectable cancers. Clin Cancer Res; 16(24); 6139-49. (C)2010 AACR. C1 [Paciotti, Giulio F.; Tamarkin, Lawrence] CytImmune Sci Inc, Rockville, MD 20850 USA. [Libutti, Steven K.; Alexander, H. Richard, Jr.; Walker, Melissa; Yuldasheva, Nargiza] NIH, Surg Branch, Ctr Canc Res, Bethesda, MD 20892 USA. [Byrnes, Adriana A.; Seidel, Geoffrey D.] SAIC Frederick Inc, Clin Monitoring Res Program, Natl Canver Inst Frederick, Frederick, MD USA. [Gannon, William E.] Capital City Tech Consulting Inc, Washington, DC USA. RP Tamarkin, L (reprint author), CytImmune Sci Inc, 9640 Med Ctr Dr, Rockville, MD 20850 USA. EM ltamarkin@cytimmune.com FU National Cancer Institute; National Institutes of Health [HHSN2612008000001E] FX This project has been funded in part with federal funds from the National Cancer Institute, National Institutes of Health, under Contract No. HHSN2612008000001E. NR 41 TC 210 Z9 216 U1 10 U2 39 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1078-0432 J9 CLIN CANCER RES JI Clin. Cancer Res. PD DEC 15 PY 2010 VL 16 IS 24 BP 6139 EP 6149 DI 10.1158/1078-0432.CCR-10-0978 PG 11 WC Oncology SC Oncology GA 695YJ UT WOS:000285408600029 PM 20876255 ER PT J AU Cohen, C Simonsen, L Kang, JW Miller, M McAnerney, J Blumberg, L Schoub, B Madhi, SA Viboud, C AF Cohen, Cheryl Simonsen, Lone Kang, Jong-Won Miller, Mark McAnerney, Jo Blumberg, Lucille Schoub, Barry Madhi, Shabir A. Viboud, Cecile TI Elevated Influenza-Related Excess Mortality in South African Elderly Individuals, 1998-2005 SO CLINICAL INFECTIOUS DISEASES LA English DT Article ID RESPIRATORY SYNCYTIAL VIRUS; UNITED-STATES; HONG-KONG; PANDEMIC INFLUENZA; VACCINATION; PNEUMONIA; IMPACT; EPIDEMICS; DEATHS; AGE AB Background. Although essential to guide control measures, published estimates of influenza-related seasonal mortality for low-and middle-income countries are few. We aimed to compare influenza-related mortality among individuals aged >= 65 years in South Africa and the United States. Methods. We estimated influenza-related excess mortality due to all causes, pneumonia and influenza, and other influenza-associated diagnoses from monthly age-specific mortality data for 1998-2005 using a Serfling regression model. We controlled for between-country differences in population age structure and nondemographic factors (baseline mortality and coding practices) by generating age-standardized estimates and by estimating the percentage excess mortality attributable to influenza. Results. Age-standardized excess mortality rates were higher in South Africa than in the United States: 545 versus 133 deaths per 100,000 population for all causes(P < .001) and 63 vs 21 deaths per 100,000 population for pneumonia and influenza (P = .03). Standardization for nondemographic factors decreased but did not eliminate between-country differences; for example, the mean percentage of winter deaths attributable to influenza was 16% in South Africa and 6% in the United States (P < .001). For all respiratory causes, cerebrovascular disease, and diabetes, age-standardized excess death rates were 4-8-fold greater in South Africa than in the United States, and the percentage increase in winter deaths attributable to influenza was 2-4-fold higher. Conclusions. These data suggest that the impact of seasonal influenza on mortality among elderly individuals may be substantially higher in an African setting, compared with in the United States, and highlight the potential for influenza vaccination programs to decrease mortality. C1 [Cohen, Cheryl; McAnerney, Jo; Blumberg, Lucille; Schoub, Barry] Univ Witwatersrand, Natl Hlth Lab Serv, Natl Inst Communicable Dis, Johannesburg, South Africa. [Cohen, Cheryl] Univ Witwatersrand, Sch Publ Hlth, Johannesburg, South Africa. [Schoub, Barry; Madhi, Shabir A.] Univ Witwatersrand, Sch Pathol, Johannesburg, South Africa. [Madhi, Shabir A.] Univ Witwatersrand, Dept Sci & Technol, Natl Res Fdn Vaccine Preventable Dis, Johannesburg, South Africa. [Simonsen, Lone] George Washington Univ, Washington, DC USA. [Simonsen, Lone; Kang, Jong-Won; Miller, Mark; Viboud, Cecile] NIH, Fogarty Int Ctr, Bethesda, MD 20892 USA. RP Cohen, C (reprint author), Natl Inst Communicable Dis, Epidemiol & Surveillance Unit, Private Bag X4, ZA-2131 Johannesburg, Gauteng, South Africa. EM cherylc@nicd.ac.za OI Simonsen, Lone/0000-0003-1535-8526 FU Office of Global Health Affairs' International Influenza Unit in the Office of the Secretary of the Department of Health and Human Services; Science and Technology Directorate, Department of Homeland Security; Fogarty International Center, National Institutes of Health; Wyeth-Pfizer; SDI Health FX This research was conducted in the context of the Multinational Influenza Seasonal Mortality Study (MISMS), an ongoing international collaborative effort to understand influenza epidemiological and evolutionary patterns, led by the Fogarty International Center, National Institutes of Health (http://www.origem.info/misms/index.php). Funding for this project comes from the Office of Global Health Affairs' International Influenza Unit in the Office of the Secretary of the Department of Health and Human Services.; Financial support. Research and Policy for Infectious Disease Dynamics (RAPIDD) program of the Science and Technology Directorate, Department of Homeland Security, and Fogarty International Center, National Institutes of Health (to L.S.).; L. S. has received funding for a research study from Wyeth-Pfizer and consulting fees from SDI Health, a data warehouse business in Plymouth Meeting, PA. All other authors: no conflicts. NR 43 TC 47 Z9 47 U1 0 U2 5 PU UNIV CHICAGO PRESS PI CHICAGO PA 1427 E 60TH ST, CHICAGO, IL 60637-2954 USA SN 1058-4838 J9 CLIN INFECT DIS JI Clin. Infect. Dis. PD DEC 15 PY 2010 VL 51 IS 12 BP 1362 EP 1369 DI 10.1086/657314 PG 8 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 681WD UT WOS:000284353100004 PM 21070141 ER PT J AU Uzel, G Orange, JS Poliak, N Marciano, BE Heller, T Holland, SM AF Uzel, Gulbu Orange, Jordan S. Poliak, Nina Marciano, Beatriz E. Heller, Theo Holland, Steven M. TI Complications of Tumor Necrosis Factor-alpha Blockade in Chronic Granulomatous Disease-Related Colitis SO CLINICAL INFECTIOUS DISEASES LA English DT Article ID CROHNS-DISEASE; INFLIXIMAB THERAPY; RHEUMATOID-ARTHRITIS; CARINII-PNEUMONIA; INTERFERON-GAMMA; INFECTION; PATIENT; MAINTENANCE; ANTIBODY; OPTIONS AB Background. Chronic granulomatous disease (CGD) is a genetic disorder of the phagocyte NADPH oxidase, which predisposes patients to infections and inflammatory complications, including severe colitis. Management of CGD colitis is a challenge because standard immunosuppressive therapy increases the risk of infection in already immunocompromised hosts. Methods. We report the use of infliximab in 5 patients with CGD. Results. Infliximab administration predisposed patients to severe infections with typical CGD pathogens but not mycobacteria, as reported with infliximab in other conditions. In addition to infections, infliximab administration led to successful closure of fistulae, sometimes with other untoward consequences. Infliximab-associated complications were associated with 2 deaths. Conclusions. Infliximab use in the treatment of CGD inflammatory bowel disease requires aggressive antimicrobial prophylaxis, assiduous surveillance for infection, and vigilance for untoward gastrointestinal complications. This experience suggests that infliximab therapy is effective but has untoward consequences in patients with CGD. C1 [Uzel, Gulbu; Marciano, Beatriz E.; Holland, Steven M.] NIAID, Lab Clin Infect Dis, NIH, Bethesda, MD 20892 USA. [Heller, Theo] NIAID, NIDDKD, NIH, Bethesda, MD 20892 USA. [Orange, Jordan S.; Poliak, Nina] Univ Penn, Childrens Hosp Philadelphia, Sch Med, Div Immunol, Philadelphia, PA 19104 USA. RP Uzel, G (reprint author), Bldg 10,CRC B3 4141,MSC 1684, Bethesda, MD 20892 USA. EM guzel@mail.nih.gov OI orange, jordan/0000-0001-7117-7725 FU National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland FX Financial support. The Intramural Research Program of the National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland. NR 38 TC 39 Z9 39 U1 0 U2 3 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 1058-4838 J9 CLIN INFECT DIS JI Clin. Infect. Dis. PD DEC 15 PY 2010 VL 51 IS 12 BP 1429 EP 1434 DI 10.1086/657308 PG 6 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 681WD UT WOS:000284353100014 PM 21058909 ER PT J AU Bausch, DG Hadi, CM Khan, SH Lertora, JJL AF Bausch, Daniel G. Hadi, Christiane M. Khan, Sheik Humarr Lertora, Juan J. L. TI Review of the Literature and Proposed Guidelines for the Use of Oral Ribavirin as Postexposure Prophylaxis for Lassa Fever SO CLINICAL INFECTIOUS DISEASES LA English DT Review ID CHRONIC HEPATITIS-C; ARGENTINE HEMORRHAGIC-FEVER; ANTIVIRAL AGENT RIBAVIRIN; VIRUS-INFECTION; INTRAVENOUS RIBAVIRIN; EPIDEMIOLOGICAL ASPECTS; DENDRITIC CELLS; CLINICAL-TRIAL; RENAL-FUNCTION; INDUCED ANEMIA AB Lassa fever is an acute viral hemorrhagic illness; the virus is endemic in West Africa and also of concern with regard to bioterrorism. Transmission of Lassa virus between humans may occur through direct contact with infected blood or bodily secretions. Oral administration of the antiviral drug ribavirin is often considered for postexposure prophylaxis, but no systematically collected data or uniform guidelines exist for this indication. Furthermore, the relatively low secondary attack rates for Lassa fever, the restriction of the area of endemicity to West Africa, and the infrequency of high-risk exposures make it unlikely that controlled prospective efficacy trials will ever be possible. Recommendations for postexposure use of ribavirin can therefore be made only on the basis of a thorough understanding and logical extrapolation of existing data. Here, we review the pertinent issues and propose guidelines based on extensive review of the literature, as well as our experience in this field. We recommend oral ribavirin postexposure prophylaxis for Lassa fever exclusively for definitive high-risk exposures. These guidelines may also serve for exposure to other hemorrhagic fever viruses susceptible to ribavirin. C1 [Bausch, Daniel G.] Tulane Univ, Tulane Sch Publ Hlth & Trop Med, Dept Trop Med, Hlth Sci Ctr, New Orleans, LA 70112 USA. [Lertora, Juan J. L.] NIH, Ctr Clin, Bethesda, MD 20892 USA. [Khan, Sheik Humarr] Kenema Govt Hosp, Minist Hlth & Sanitat, Kenema, Sierra Leone. RP Bausch, DG (reprint author), Tulane Univ, Tulane Sch Publ Hlth & Trop Med, Dept Trop Med, Hlth Sci Ctr, SL-17,1430 Tulane Ave, New Orleans, LA 70112 USA. EM dbausch@tulane.edu FU Tulane University FX Financial support. Tulane University. NR 86 TC 43 Z9 44 U1 2 U2 17 PU UNIV CHICAGO PRESS PI CHICAGO PA 1427 E 60TH ST, CHICAGO, IL 60637-2954 USA SN 1058-4838 J9 CLIN INFECT DIS JI Clin. Infect. Dis. PD DEC 15 PY 2010 VL 51 IS 12 BP 1435 EP 1441 DI 10.1086/657315 PG 7 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 681WD UT WOS:000284353100015 PM 21058912 ER PT J AU Morens, DM Taubenberger, JK Folkers, GK Fauci, AS AF Morens, David M. Taubenberger, Jeffery K. Folkers, Gregory K. Fauci, Anthony S. TI Pandemic Influenza's 500th Anniversary SO CLINICAL INFECTIOUS DISEASES LA English DT Editorial Material AB It is impossible to know with certainty the first time that an influenza virus infected humans or when the first influenza pandemic occurred. However, many historians agree that the year 1510 A.D.-500 years ago-marks the first recognition of pandemic influenza. On this significant anniversary it is timely to ask: what were the circumstances surrounding the emergence of the 1510 pandemic, and what have we learned about this important disease over the subsequent five centuries? We conclude that in recent decades significant progress has been made in diagnosis, prevention, control, and treatment of influenza. It seems likely that, in the foreseeable future, we may be able to greatly reduce the burden of influenza pandemics with improved vaccines and other scientific and public health approaches. C1 [Morens, David M.; Taubenberger, Jeffery K.; Folkers, Gregory K.; Fauci, Anthony S.] NIAID, NIH, Bethesda, MD 20892 USA. RP Morens, DM (reprint author), NIAID, NIH, Bldg 31,Rm 7A-03,31 Ctr Dr, Bethesda, MD 20892 USA. EM dm260q@nih.gov FU Intramural NIH HHS NR 15 TC 16 Z9 17 U1 0 U2 4 PU UNIV CHICAGO PRESS PI CHICAGO PA 1427 E 60TH ST, CHICAGO, IL 60637-2954 USA SN 1058-4838 J9 CLIN INFECT DIS JI Clin. Infect. Dis. PD DEC 15 PY 2010 VL 51 IS 12 BP 1442 EP 1444 DI 10.1086/657429 PG 3 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 681WD UT WOS:000284353100016 PM 21067353 ER PT J AU Balamurugan, K Wang, JM Tsai, HH Sharan, S Anver, M Leighty, R Sterneck, E AF Balamurugan, Kuppusamy Wang, Ju-Ming Tsai, Hsin-Hwa Sharan, Shikha Anver, Miriam Leighty, Robert Sterneck, Esta TI The tumour suppressor C/EBP delta inhibits FBXW7 expression and promotes mammary tumour metastasis SO EMBO JOURNAL LA English DT Article DE hypoxia; mammary tumour; metastasis; protein stability; protein translation ID BINDING-PROTEIN-DELTA; CELL-CYCLE ARREST; HYPOXIA-INDUCIBLE FACTORS; GENE-EXPRESSION; BREAST-CANCER; INNATE IMMUNITY; FACTOR-1 HIF-1; FANCONI-ANEMIA; HIF-1-ALPHA; PATHWAY AB Inflammation and hypoxia are known to promote the metastatic progression of tumours. The CCAAT/enhancer-binding protein-delta (C/EBP delta, CEBPD) is an inflammatory response gene and candidate tumour suppressor, but its physiological role in tumourigenesis in vivo is unknown. Here, we demonstrate a tumour suppressor function of C/EBP delta using transgenic mice overexpressing the Neu/Her2/ERBB2 proto-oncogene in the mammary gland. Unexpectedly, this study also revealed that C/EBP delta is necessary for efficient tumour metastasis. We show that C/EBP delta is induced by hypoxia in tumours in vivo and in breast tumour cells in vitro, and that C/EBP delta-deficient cells exhibit reduced glycolytic metabolism and cell viability under hypoxia. C/EBP delta supports CXCR4 expression. On the other hand, C/EBP delta directly inhibits expression of the tumour suppressor F-box and WD repeat-domain containing 7 gene (FBXW7, FBW7, AGO, Cdc4), encoding an F-box protein that promotes degradation of the mammalian target of rapamycin (mTOR). Consequently, C/EBP delta enhances mTOR/AKT/S6K1 signalling and augments translation and activity of hypoxia-inducible factor-1 alpha (HIF-1 alpha), which is necessary for hypoxia adaptation. This work provides new insight into the mechanisms by which metastasis-promoting signals are induced specifically under hypoxia. The EMBO Journal (2010) 29, 4106-4117. doi: 10.1038/emboj.2010.280; Published online 12 November 2010 C1 [Balamurugan, Kuppusamy; Sharan, Shikha; Sterneck, Esta] NCI, Lab Cell & Dev Signalling, CCR, Frederick, MD 21702 USA. [Wang, Ju-Ming; Tsai, Hsin-Hwa] Natl Cheng Kung Univ, Coll Biosci & Biotechnol, Inst Bioinformat & Biosignal Transduct, Tainan 70101, Taiwan. [Anver, Miriam] NCI, Pathol Histotechnol Lab, SAIC Frederick, Frederick, MD 21702 USA. [Leighty, Robert] NCI, Data Management Serv Inc, Frederick, MD 21702 USA. RP Sterneck, E (reprint author), NCI, Lab Cell & Dev Signalling, CCR, 1050 Boyles St,Bldg 560, Frederick, MD 21702 USA. EM sternecg@mail.nih.gov FU NIH, National Cancer Institute; Federal Funds [HHSN261200800001E] FX We are indebted to Glenn Summers and the SAIC Animal Sciences Program for outstanding technical support, Donna Butcher for superb immunohistochemistry services, Linda Miller for genotyping, Simona Florea for quantification of lung metastases, Melinda Hollingshead for teaching us tumour cell isolation and Stephen Lockett and Larry Sternberg for help with image capture and analysis. For generously providing reagents, we thank Giovanni Mellilo and Annamaria Rapisarda (U251-HRE cells), Valery Bliskovsky and Beverly Mock (mTOR expression construct) and William Muller and Jeff Green (MMTV-c-Neu transgenic mice). We thank Debbie Liao and Randall S Johnson for advice and sharing unpublished data. We thank Douglas Lowy, Lalage Wakefield, Giovanni Melillo, Ira Daar, Jun Wang and Tapasree Roy Sarkar for invaluable discussion and critical comments on the paper, and Richard Frederickson for preparation of the figures. This research was supported by the Intramural Research Program of the NIH, National Cancer Institute and, in part, by Federal Funds under contract no. HHSN261200800001E. Balamurugan, Sterneck and Wang planned the experiments; Balamurugan, Wang, Tsai and Sharan executed experiments; Balamurugan, Sterneck, Leighty, Anver and Wang analysed the data; and Balamurugan and Sterneck wrote the paper. NR 69 TC 52 Z9 53 U1 1 U2 11 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0261-4189 J9 EMBO J JI Embo J. PD DEC 15 PY 2010 VL 29 IS 24 BP 4106 EP 4117 DI 10.1038/emboj.2010.280 PG 12 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 695XX UT WOS:000285407200007 PM 21076392 ER PT J AU Schecter, A Malik, N Haffner, D Smith, S Harris, TR Paepke, O Birnbaum, L AF Schecter, Arnold Malik, Noor Haffner, Darrah Smith, Sarah Harris, T. Robert Paepke, Olaf Birnbaum, Linda TI Bisphenol A (BPA) in U.S. Food SO ENVIRONMENTAL SCIENCE & TECHNOLOGY LA English DT Article ID PERFORMANCE LIQUID-CHROMATOGRAPHY; IN-UTERO EXPOSURE; DEVELOPMENTAL EXPOSURE; RISK-ASSESSMENT; CANNED FOODS; HUMAN HEALTH; BREAST-MILK; MIGRATION; MICE; COATINGS AB Bisphenol A (BPA) is a chemical used for lining metal cans and in polycarbonate plastics, such as baby bottles. In rodents, BPA is associated with early sexual maturation, altered behavior, and effects on prostate and mammary glands. In humans, BPA is associated with cardiovascular disease, diabetes, and male sexual dysfunction in exposed workers. Food is a major exposure source. We know of no studies reporting BPA in U.S. fresh food, canned food, and food in plastic packaging in peer reviewed journals. We measured BPA levels in 105 fresh and canned foods, foods sold in plastic packaging, and in cat and dog foods in cans and plastic packaging. We detected BPA in 63 of 105 samples, including fresh turkey, canned green beans, and canned infant formula. Ninety-three of these samples were triplicates which had similar detected levels. Detected levels ranged from 0.23 to 65.0 ng/g ww and were not associated with type of food or packaging but did vary with pH. BPA levels were higher for foods of pH 5 compared to more acidic and alkaline foods. Detected levels were comparable to those found by others. Further research is indicated to determine BPA levels in U.S. food in larger, representative sampling. C1 [Schecter, Arnold; Malik, Noor; Smith, Sarah; Harris, T. Robert] Univ Texas Dallas, Sch Publ Hlth, Dallas, TX 75390 USA. [Haffner, Darrah] Univ Texas SW Med Ctr Dallas, Dallas, TX 75390 USA. [Birnbaum, Linda] NCI, Bethesda, MD 20892 USA. [Paepke, Olaf] Eurofins Gfa GmbH Lab, D-21079 Hamburg, Germany. RP Schecter, A (reprint author), Univ Texas Dallas, Sch Publ Hlth, 6011 Harry Hines Blvd,V8-112, Dallas, TX 75390 USA. EM Arnold.Schecter@UTSouthwestern.edu OI zaraat, javad/0000-0001-5341-7481 FU Gustavus and Louise Pfeiffer Research Foundation FX This study was funded by a grant from the Gustavus and Louise Pfeiffer Research Foundation. We thank Consumers Union and the Environmental Working Group for generously sharing their findings with us. Disclaimer: This manuscript does not reflect NIEHS/NIH policy. NR 53 TC 103 Z9 108 U1 10 U2 76 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0013-936X J9 ENVIRON SCI TECHNOL JI Environ. Sci. Technol. PD DEC 15 PY 2010 VL 44 IS 24 BP 9425 EP 9430 DI 10.1021/es102785d PG 6 WC Engineering, Environmental; Environmental Sciences SC Engineering; Environmental Sciences & Ecology GA 694AK UT WOS:000285266900030 PM 21038926 ER PT J AU Germain, RN AF Germain, Ronald N. TI Computational analysis of T cell receptor signaling and ligand discrimination - Past, present, and future SO FEBS LETTERS LA English DT Review DE T Cell receptor; Receptor signaling; T Lymphocyte; Computational modeling; Antigen discrimination ID CYTOPLASMIC FREE CALCIUM; IMMUNOLOGICAL SYNAPSE; ANTIGEN RECEPTOR; IMMUNE-SYSTEM; ANTAGONIST LIGANDS; NEGATIVE FEEDBACK; CUTTING EDGE; ACTIVATION; COMPLEX; PROTEIN AB Signaling through the T cell receptor for antigen (TCR) has been studied for years by conventional biochemical means. More recently, attempts have been made to develop computational models of signaling through this receptor, with a specific focus on understanding how this recognition system discriminates between closely related (self and non-self) ligands. Here we discuss recent advances centered on the role of feedback regulation, especially the key finding that a combination of digital and analog control circuits is fundamental to the discrimination properties of the TCR. We end by pointing to future, more biologically accurate models that incorporate spatial aspects of molecular organization in antigen-engaged T lymphocytes with this underlying biochemistry. Published by Elsevier B.V. on behalf of the Federation of European Biochemical Societies. C1 NIAID, Lymphocyte Biol Sect,Trans NIH Ctr Human Immunol, Immunol Lab,NIH,DHHS, Program Syst Immunol & Infect Dis Modeling PSIIM, Bethesda, MD 20892 USA. RP Germain, RN (reprint author), NIAID, Lymphocyte Biol Sect,Trans NIH Ctr Human Immunol, Immunol Lab,NIH,DHHS, Program Syst Immunol & Infect Dis Modeling PSIIM, Bldg 10,Rm 11N311,10 Ctr Dr,MSC-1892, Bethesda, MD 20892 USA. EM rgermain@nih.gov FU National Institute of Allergy and Infectious Diseases, National Institutes of Health FX I wish to acknowledge the critical contributions made to the research and concepts discussed in this review by colleagues and collaborators, especially I. Stefanova, Gregoire Altan-Bonnet, and Martin Meier-Schellersheim, as well as J. Madrenas, L. Racioppi, and L. Samelson. As with any brief review, I apologize to those investigators whose work could not be cited explicitly due to length and space constraints. This work was supported by the Intramural Research Program of the National Institute of Allergy and Infectious Diseases, National Institutes of Health. NR 75 TC 4 Z9 4 U1 3 U2 12 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0014-5793 J9 FEBS LETT JI FEBS Lett. PD DEC 15 PY 2010 VL 584 IS 24 BP 4814 EP 4822 DI 10.1016/j.febslet.2010.10.027 PG 9 WC Biochemistry & Molecular Biology; Biophysics; Cell Biology SC Biochemistry & Molecular Biology; Biophysics; Cell Biology GA 689QO UT WOS:000284943600002 PM 20965176 ER PT J AU Siraganian, RP de Castro, RO Barbu, EA Zhang, JA AF Siraganian, Reuben P. de Castro, Rodrigo O. Barbu, Emilia A. Zhang, Juan TI Mast cell signaling: The role of protein tyrosine kinase Syk, its activation and screening methods for new pathway participants SO FEBS LETTERS LA English DT Review DE Mast cell; Fc epsilon RI signal transduction; Syk; Fyn; Gab2; Phosphatase ID FC-EPSILON-RI; AFFINITY IGE RECEPTOR; BASOPHILIC LEUKEMIA-CELLS; LOOP TYROSINES; LINKER REGION; C-CBL; PHOSPHORYLATION; DEGRANULATION; P72(SYK); TRANSDUCTION AB The aggregation by antigen of the IgE bound to its high affinity receptor on mast cells initiates a complex series of biochemical events that result in the release of inflammatory mediators. The essential role of the protein tyrosine kinase Syk has been appreciated for some time, and newer results have defined the mechanism of its activation. The use of siRNA has defined the relative contribution of Syk, Fyn and Gab2 to signaling and has made possible a screening study to identify previously unrecognized molecules that are involved in these pathways. Published by Elsevier B.V. on behalf of the Federation of European Biochemical Societies. C1 [Siraganian, Reuben P.; de Castro, Rodrigo O.; Barbu, Emilia A.; Zhang, Juan] Natl Inst Dent & Craniofacial Res, Receptors & Signal Transduct Sect, NIH, Bethesda, MD 20892 USA. RP Siraganian, RP (reprint author), Natl Inst Dent & Craniofacial Res, Receptors & Signal Transduct Sect, NIH, Bldg 49,Rm 1A16, Bethesda, MD 20892 USA. EM rs53x@nih.gov FU National Institutes of Health, NIDCR FX We thank Jacqueline Groves for helpful discussions and review of the manuscript; we also thank William Swaim for help with morphological experiments. This work was supported by the Intramural Research Program of the National Institutes of Health, NIDCR. NR 50 TC 36 Z9 39 U1 0 U2 7 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0014-5793 J9 FEBS LETT JI FEBS Lett. PD DEC 15 PY 2010 VL 584 IS 24 BP 4933 EP 4940 DI 10.1016/j.febslet.2010.08.006 PG 8 WC Biochemistry & Molecular Biology; Biophysics; Cell Biology SC Biochemistry & Molecular Biology; Biophysics; Cell Biology GA 689QO UT WOS:000284943600018 PM 20696166 ER PT J AU Correa, CR Li, L Aldini, G Carini, M Chen, CYO Chun, HK Cho, SM Park, KM Russell, RM Blumberg, JB Yeum, KJ AF Correa, Camila R. Li, Lei Aldini, Giancarlo Carini, Marina Chen, C. -Y. Oliver Chun, Hye-Kyung Cho, Soo-Muk Park, Ki-Moon Russell, Robert M. Blumberg, Jeffrey B. Yeum, Kyung-Jin TI Composition and stability of phytochemicals in five varieties of black soybeans (Glycine max) SO FOOD CHEMISTRY LA English DT Article DE Glycine max; Variety; Stability; Lutein; Tocopherol; Daidzein; Genistein ID DENSITY-LIPOPROTEIN OXIDATION; ABSORBENCY CAPACITY ASSAY; ANTIOXIDANT ACTIVITIES; MASS-SPECTROMETRY; SERUM-LIPIDS; VITAMIN-C; L. MERR.; SUPPLEMENTATION; ANTHOCYANINS; IDENTIFICATION AB Phytochemical compositions of five varieties of black soybeans (Glycine max) and their stabilities at room temperature, 4 and -80 degrees C over 14 months were determined by HPLC systems with electrochemical (ECD) and UV detectors. Polyphenol profiling was carried out by a liquid chromatography-electrospray ionisation-mass spectrometry (LC-ESI-MS) with orbitrap as a mass analyser in both positive and negative ion modes, and polyphenols in aglycone forms were quantified by HPLC-ECD. Five different varieties of black soybeans (G. max) contained 249-405 mu g/g dry wt of gamma-tocopherol and 6.76-14.98 mu g/g dry wt of lutein. Major polyphenols in black soybeans (G. max) were daidzein (193-288 mu g/g dry wt) and genistein (145-223 mu g/g dry wt), mainly present as glucosides and acetyl glucosides. No significant decrease was found in total phenols of black soybeans (G. max) stored at room temperature, 4 or -80 degrees C for 14 months. On the other hand, lutein and gamma-tocopherol degraded significantly within a month of storage at room temperature (p < 0.01), whereas they remained stable up to 6 months at 4 C and up to 14 months at -80 degrees C. The current study indicates that black soybeans (G. max) are rich source of gamma-tocopherol and phenols (isoflavones, flavonols, flavan-3-ols, proanthocyanidins and anthocyanin) and that the levels vary depending upon varieties. In addition, storage at low temperature is recommended to reduce the loss of fat-soluble phytochemicals in black soybeans (G. max) over an extended period of time. (C) 2010 Elsevier Ltd. All rights reserved. C1 [Correa, Camila R.; Li, Lei; Chen, C. -Y. Oliver; Blumberg, Jeffrey B.; Yeum, Kyung-Jin] Tufts Univ, Jean Mayer USDA Human Res Ctr Ageing, Boston, MA 02111 USA. [Li, Lei] Qingdao Univ, Coll Med, Qingdao 266021, Shandong, Peoples R China. [Aldini, Giancarlo; Carini, Marina] Univ Milan, Dept Pharmaceut Sci Pietro Pratesi, Milan, Italy. [Chun, Hye-Kyung; Cho, Soo-Muk] Rural Dev Adm, Natl Acad Agr Sci, Seoul, South Korea. [Park, Ki-Moon] Sungkyunkwan Univ, Dept Food Sci & Biotechnol, Suwon 440746, South Korea. [Russell, Robert M.] NIH, Off Director, Washington, DC USA. RP Yeum, KJ (reprint author), Tufts Univ, Jean Mayer USDA Human Res Ctr Ageing, 711 Washington St, Boston, MA 02111 USA. EM kyungjin.yeum@Tufts.edu RI CARINI, MARINA/D-3084-2015; OI CARINI, MARINA/0000-0003-3407-5425; aldini, giancarlo/0000-0002-2355-6744 FU BioGreen 21 Program [20070301034009]; Rural Development Administration; Korea and US Department of Agriculture [1950-51000-065-08S] FX This research has been supported in part by the BioGreen 21 Program (Code #20070301034009), Rural Development Administration, Korea and US Department of Agriculture, under Agreement 1950-51000-065-08S. The contents of this publication do not necessarily reflect the views or policies of the US Department of Agriculture, nor does mention of trade names, commercial products, or organizations imply endorsement by the US Government. NR 28 TC 18 Z9 18 U1 5 U2 32 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0308-8146 J9 FOOD CHEM JI Food Chem. PD DEC 15 PY 2010 VL 123 IS 4 BP 1176 EP 1184 DI 10.1016/j.foodchem.2010.05.083 PG 9 WC Chemistry, Applied; Food Science & Technology; Nutrition & Dietetics SC Chemistry; Food Science & Technology; Nutrition & Dietetics GA 639XL UT WOS:000281010300032 ER PT J AU Parkin, DM Ferlay, J Curado, MP Bray, F Edwards, B Shin, HR Forman, D AF Parkin, D. Max Ferlay, Jacques Curado, Maria-Paula Bray, Freddie Edwards, Brenda Shin, Hai-Rim Forman, David TI Fifty years of cancer incidence: CI5 I-IX SO INTERNATIONAL JOURNAL OF CANCER LA English DT Article DE cancer registry; incidence; trend; internet ID MORTALITY; ADENOCARCINOMA; STATISTICS; CERVIX; TRENDS AB The Cancer Incidence in Five Continents (CI5) series comprises nine volumes that bring together peer-reviewed results from population-based cancer registries worldwide. The aim of each is to make available comparable data on cancer incidence from as wide a range of geographical locations as possible. In addition, the existence of long time series of data allows the evolution of risk in different populations over time to be studied. The CI5 I-IX database brings together the results from all nine volumes, spanning a period of some 50 years. In addition, unpublished annual data, with more diagnostic detail, are made available for many cancer registries with 15 or more years of recent data. We describe the construction and composition of the CI5 databases, and provide examples of how they can be used to prepare tables and graphs comparing incidence rates between populations. This is the classical role of descriptive statistics: to allow formulation of hypotheses that might explain the observed differences (geographically, over time, in population subgroups) and that can be tested by further study. Such statistics are also essential components in the planning and evaluation of cancer control programmes. C1 [Parkin, D. Max] Univ Oxford, Clin Trials Serv Unit, Oxford OX3 7LF, England. [Parkin, D. Max] Univ Oxford, Epidemiol Studies Unit, Oxford OX3 7LF, England. [Ferlay, Jacques; Curado, Maria-Paula; Bray, Freddie; Shin, Hai-Rim; Forman, David] Int Agcy Res Canc, Canc Informat Sect, F-69372 Lyon, France. [Edwards, Brenda] NCI, Bethesda, MD 20892 USA. RP Parkin, DM (reprint author), Univ Oxford, Clin Trials Serv Unit, Richard Doll Bldg,Old Rd Campus, Oxford OX3 7LF, England. EM max.parkin@ctsu.ox.ac.uk RI Curado, Maria Paula/M-6200-2013 OI Curado, Maria Paula/0000-0001-8172-2483 NR 32 TC 68 Z9 74 U1 1 U2 9 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0020-7136 J9 INT J CANCER JI Int. J. Cancer PD DEC 15 PY 2010 VL 127 IS 12 BP 2918 EP 2927 DI 10.1002/ijc.25517 PG 10 WC Oncology SC Oncology GA 680CA UT WOS:000284208400018 PM 21351270 ER PT J AU Sherman, KE Andersen, JW Butt, AA Umbleja, T Alston, B Koziel, MJ Peters, MG Sulkowski, M Goodman, ZD Chung, RT AF Sherman, Kenneth E. Andersen, Janet W. Butt, Adeel A. Umbleja, Triin Alston, Beverly Koziel, Margaret J. Peters, Marion G. Sulkowski, Mark Goodman, Zachary D. Chung, Raymond T. CA AIDS Clinical Trials Grp A5178 Stu TI Sustained Long-Term Antiviral Maintenance Therapy in HCV/HIV-Coinfected Patients (SLAM-C) SO JAIDS-JOURNAL OF ACQUIRED IMMUNE DEFICIENCY SYNDROMES LA English DT Article DE fibrosis; HCV; HIV; maintenance; racial disparity ID CHRONIC HEPATITIS-C; HUMAN-IMMUNODEFICIENCY-VIRUS; HIV-INFECTED PATIENTS; PROTEASE INHIBITOR THERAPY; ALPHA-2A PLUS RIBAVIRIN; LIVER-DISEASE; INTERFERON THERAPY; HEPATOCELLULAR-CARCINOMA; ANTIRETROVIRAL THERAPY; FIBROSIS PROGRESSION AB Background: Hepatitis C virus (HCV)/HIV coinfection treatment is suboptimal with low sustained viral response rates to standard therapies. A multicenter randomized clinical trial designed to assess the efficacy/safety of pegylated interferon maintenance therapy was performed by the National Institutes of Health-funded AIDS Clinical Trials Group network. Methods: HCV treatment-naive and nonresponding interferon-experienced subjects with confirmed HCV and HIV, CD4 > 200 cells per cubic millimeter, and at least stage 1 fibrosis were enrolled and treated for 12 weeks with pegylated interferon alfa 2a 180 mcg per week (PEG) + weight-based ribavirin to determine response status. Nonresponder subjects (failure to clear HCV RNA or achieve 2-log drop) underwent liver biopsy and were randomized to receive full dose PEG or observation only for 72 weeks. Paired biopsies were evaluated by a central pathologist. Results: Three hundred thirty subjects were enrolled; median age was 48 years; 43% white, 37% black, non-Hispanic; 83% male; CD4+ 498 cells per cubic millimeter; 32% were interferon experienced; 74% had entry HIV RNA <50 copies per milliliter. early virologic responder was observed in 55.9% and 42.5% achieved complete Early Viral Response (cEVR). A planned interim analysis of occurred when 84 subjects were randomized. With data on 40 paired biopsies available, a safety monitoring board stopped the trial due to lack of fibrosis progression (median = 0 Metavir units/year) in the observation arm. Conclusions: Lack of fibrotic progression in the control arm was unexpected and may represent a short-term PEG/ribavirin therapy effect, high levels of HIV viral suppression, and use of antiretroviral regimens that may be less toxic than prior generations of therapy. C1 [Sherman, Kenneth E.] Univ Cincinnati, Coll Med, Div Digest Dis, Dept Internal Med, Cincinnati, OH 45267 USA. [Andersen, Janet W.; Umbleja, Triin] Harvard Univ, Sch Publ Hlth, Ctr Biostat AIDS Res, Boston, MA 02115 USA. [Butt, Adeel A.] Univ Pittsburgh, Div Infect Dis, Pittsburgh, PA USA. [Alston, Beverly] NIAID, Div Aids, Bethesda, MD 20892 USA. [Koziel, Margaret J.] Beth Israel Deaconess Med Ctr, Harvard Inst Med, Boston, MA 02215 USA. [Peters, Marion G.] Univ Calif San Francisco, Dept Gastroenterol, San Francisco, CA 94143 USA. [Sulkowski, Mark] Johns Hopkins Univ, Div Infect Dis & Gastroenterol Hepatol, Baltimore, MD USA. [Goodman, Zachary D.] Armed Forces Inst Pathol, Washington, DC 20306 USA. [Chung, Raymond T.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Med, Boston, MA USA. RP Sherman, KE (reprint author), Univ Cincinnati, Coll Med, Div Digest Dis, Dept Internal Med, 231 Albert Sabin Way, Cincinnati, OH 45267 USA. EM kenneth.sherman@uc.edu FU National Institute of Allergy and Infectious Diseases [U01 AI068634, U01 AI38858, U01 AI068636]; NIDDK [K24 DK070528, RO1 16065]; National Center for Research Resources; Roche Pharmaceuticals FX The project described was supported by National Institute of Allergy and Infectious Diseases funding to the AIDS Clinical Trials Group including U01 AI068634, U01 AI38858, U01 AI068636, an NIDDK K24 DK070528 to K.E.S., and an RO1 16065 to M.S. Also supported in part by the General Clinical Research Center Units funded by the National Center for Research Resources. Study drug and other support was provided by Roche Pharmaceuticals. Statistical analysis of the entire data sets pertaining to efficacy and safety have been independently confirmed by a biostatistician who is not employed by the corporate entity. NR 32 TC 17 Z9 17 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1525-4135 J9 JAIDS-J ACQ IMM DEF JI JAIDS PD DEC 15 PY 2010 VL 55 IS 5 BP 597 EP 605 DI 10.1097/QAI.0b013e3181f6d916 PG 9 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA 679FR UT WOS:000284147500011 PM 20921898 ER PT J AU Hodder, SL Justman, J Haley, DE Adimora, AA Fogel, CI Golin, CE O'Leary, A Soto-Torres, L Wingood, G El-Sadr, WM AF Hodder, Sally L. Justman, Jessica Haley, Danielle E. Adimora, Adaora A. Fogel, Catherine I. Golin, Carol E. O'Leary, Ann Soto-Torres, Lydia Wingood, Gina El-Sadr, Wafaa M. CA Hiv Prevention Trials Network Dome TI Challenges of a Hidden Epidemic: HIV Prevention Among Women in the United States SO JAIDS-JOURNAL OF ACQUIRED IMMUNE DEFICIENCY SYNDROMES LA English DT Article DE HIV in women; HIV prevention science; racial disparity ID SEXUALLY-TRANSMITTED-DISEASE; AFRICAN-AMERICAN WOMEN; RANDOMIZED CONTROLLED-TRIAL; BEHAVIORAL INTERVENTIONS; CONCURRENT PARTNERSHIPS; RACIAL DISPARITIES; INFECTIOUS-DISEASE; SOCIAL-CONTEXT; RISK BEHAVIOR; DOUBLE-BLIND AB HIV/AIDS trends in the United States depict a concentrated epidemic with hot spots that vary by location, poverty, race/ethnicity, and transmission mode. HIV/AIDS is a leading cause of death among US women of color; two-thirds of new infections among women occur in black women, despite the fact that black women account for just 14% of the US female population. The gravity of the HIV epidemic among US women is often not appreciated by those at risk and by the broader scientific community. We summarize the current epidemiology of HIV/AIDS among US women and discuss clinical, research, and public health intervention components that must be brought together in a cohesive plan to reduce new HIV infections in US women. Only by accelerating research and programmatic efforts will the hidden epidemic of HIV among US women emerge into the light and come under control. C1 [Hodder, Sally L.] Univ Med & Dent New Jersey, New Jersey Med Sch, Newark, NJ 07101 USA. [Justman, Jessica; El-Sadr, Wafaa M.] Columbia Univ, Int Ctr AIDS Care & Treatment Programs, Mailman Sch Publ Hlth, New York, NY USA. [Justman, Jessica; El-Sadr, Wafaa M.] Columbia Univ, Coll Phys & Surg, New York, NY USA. [Haley, Danielle E.] FHI, Durham, NC USA. [Adimora, Adaora A.] Univ N Carolina, Sch Med, Chapel Hill, NC USA. [Fogel, Catherine I.] Univ N Carolina, Sch Nursing, Chapel Hill, NC USA. [Golin, Carol E.] Univ N Carolina, Sch Publ Hlth, Chapel Hill, NC USA. [O'Leary, Ann] Ctr Dis Control & Prevent, Atlanta, GA USA. [Soto-Torres, Lydia] NIH, Div Aids, Bethesda, MD 20892 USA. [Wingood, Gina] Emory Univ, Rollins Sch Publ Hlth, Atlanta, GA 30322 USA. [El-Sadr, Wafaa M.] Harlem Hosp Med Ctr, New York, NY USA. RP Hodder, SL (reprint author), Univ Med & Dent New Jersey, New Jersey Med Sch, 185 S Orange Ave,MSB I-510, Newark, NJ 07101 USA. EM hoddersa@umdnj.edu FU HIV Prevention Trials Network (HPTN); National Institute of Allergy and Infectious Disease and the National Institute of Mental Health, both in Bethesda, MD [U01 AIO68619, U01 AI068619]; National Institute of Allergy and Infectious Disease and the National Institute of Mental Health [U01 AIO68619, U01 AI068619, U01 AI069466-0351, U01 AI069466, AI06819, U01 AIO69423, U01 AI069423]; Emory Center for AIDS Research, Atlanta, GA [P30 AI050409] FX This project was supported by the HIV Prevention Trials Network and sponsored by the National Institute of Allergy and Infectious Disease and the National Institute of Mental Health, both in Bethesda, MD, under award number U01 AIO68619. The authors' work on this article was supported in part by grants from National Institute of Allergy and Infectious Disease and the National Institute of Mental Health, under award numbers U01 AI069466-0351 (Dr S.L.H.), U01 AI069466 (Dr W.M.E. and Dr J.J.), AI06819 (Dr J.J.), U01 AIO68619 (Ms D.F.H.), and U01 AIO69423 (Dr A.A.A., Dr C.I.F., and Dr C.E.G.); and the Emory Center for AIDS Research, Atlanta, GA, under award number P30 AI050409 (Dr G.W.).; The authors wish to acknowledge the contributions of Drs. Sten Vermund, Quarraisha Abdool-Karim, David Metzger; Nirupama Sista and Ms. Harmony Waller This project was supported by the HIV Prevention Trials Network (HPTN) and sponsored by the National Institute of Allergy and Infectious Diseases (MAID) in Bethesda, MD, under award number U01 AI068619. The authors' work on this manuscript was supported in part by grants from NIAID and NIMH, under award numbers U01 AI069466 (Dr Hodder), U01 AI069466 (Dr El-Sadr and Dr Justman), AI06819 (Dr Justman), U01 AI068619 (Ms Haley), and U01 AI069423 (Dr Adimora, Dr Fogel, and Dr Golin); and the Emory Center for AIDS Research, Atlanta, GA, under award number P30 AI050409 (Dr Wingood). The views expressed herein are solely the responsibility of the authors and do not necessarily represent the official views of NIAID, NIH, the HPTN, the Centers for Disease Control and Prevention, or its funders. NR 66 TC 34 Z9 35 U1 4 U2 12 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1525-4135 J9 JAIDS-J ACQ IMM DEF JI JAIDS PD DEC 15 PY 2010 VL 55 SU 2 BP S69 EP S73 DI 10.1097/QAI.0b013e3181fbbdf9 PG 5 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA 689YD UT WOS:000284966100003 PM 21406990 ER PT J AU Millett, GA Crowley, JS Koh, H Valdiserri, RO Frieden, T Dieffenbach, CW Fenton, KA Benjamin, R Whitescarver, J Mermin, J Parham-Hopson, D Fauci, AS AF Millett, Gregorio A. Crowley, Jeffrey S. Koh, Howard Valdiserri, Ronald O. Frieden, Thomas Dieffenbach, Carl W. Fenton, Kevin A. Benjamin, Regina Whitescarver, Jack Mermin, Jonathan Parham-Hopson, Deborah Fauci, Anthony S. TI A Way Forward: The National HIV/AIDS Strategy and Reducing HIV Incidence in the United States SO JAIDS-JOURNAL OF ACQUIRED IMMUNE DEFICIENCY SYNDROMES LA English DT Article DE HIV/AIDS; National; Obama; President; strategy ID ANTIRETROVIRAL THERAPY; SEXUAL TRANSMISSION; INFECTION; METAANALYSIS; DISPARITIES; PREVENTION; BEHAVIOR; HEALTH; CARE AB In July 2010, the Obama Administration released a National HIV/AIDS Strategy for the United States to refocus national attention on responding to the domestic HIV epidemic. The goals of the strategy are to reduce HIV incidence; to increase access to care and optimize health outcomes among people living with HIV; and to reduce HIV-related disparities. The strategy identifies a small number of action steps that will align efforts across federal, state, local, and tribal levels of government, and maximally impact the domestic HIV epidemic. In this article, we outline key programmatic and research issues that must be addressed to accomplish the prevention goals of the National HIV/AIDS Strategy. C1 [Millett, Gregorio A.; Crowley, Jeffrey S.] White House, Off Natl AIDS Policy, Washington, DC 20502 USA. [Frieden, Thomas] Off Director, Ctr Dis Control & Prevent, Atlanta, GA USA. [Koh, Howard; Valdiserri, Ronald O.] Off Publ Hlth & Sci, Dept Hlth & Human Serv, Rockville, MD USA. [Dieffenbach, Carl W.] NIAID, Div Aids, NIH, Bethesda, MD 20892 USA. [Fenton, Kevin A.; Mermin, Jonathan] Ctr Dis Control & Prevent, Natl Ctr HIV AIDS Viral Hepatitis STD & TB Preven, Atlanta, GA USA. [Benjamin, Regina] Off Surg Gen, Dept Hlth & Human Serv, Rockville, MD USA. [Whitescarver, Jack] Off AIDS Res, Off Director, NIH, Bethesda, MD USA. [Parham-Hopson, Deborah] NIAID, HIV AIDS Bur, Hlth Resources & Serv Adm, NIH, Bethesda, MD 20892 USA. [Fauci, Anthony S.] NIAID, Off Director, NIH, Bethesda, MD 20892 USA. RP Millett, GA (reprint author), White House, Off Natl AIDS Policy, Washington, DC 20502 USA. EM gmillett@who.eop.gov RI Mermin, Jonathan/J-9847-2012 NR 25 TC 38 Z9 38 U1 3 U2 12 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1525-4135 J9 JAIDS-J ACQ IMM DEF JI JAIDS PD DEC 15 PY 2010 VL 55 SU 2 BP S144 EP S147 DI 10.1097/QAI.0b013e3181fbcb04 PG 4 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA 689YD UT WOS:000284966100019 PM 21406986 ER PT J AU Grady, C AF Grady, Christine TI Institutional Review Boards and Protecting Human Research Participants Reply SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Letter C1 NIH, Dept Bioeth, Ctr Clin, Bethesda, MD 20892 USA. RP Grady, C (reprint author), NIH, Dept Bioeth, Ctr Clin, Bldg 10, Bethesda, MD 20892 USA. EM cgrady@nih.gov NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610-0946 USA SN 0098-7484 J9 JAMA-J AM MED ASSOC JI JAMA-J. Am. Med. Assoc. PD DEC 15 PY 2010 VL 304 IS 23 BP 2592 EP 2592 DI 10.1001/jama.2010.1823 PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA 694MX UT WOS:000285303400020 ER PT J AU Song, M Zhang, SY Xu, XY Hang, TJ Jia, L AF Song, Min Zhang, Siyun Xu, Xiaoyan Hang, Taijun Jia, Lee TI Simultaneous determination of three Panax notoginseng saponins at sub-nanograms by LC-MS/MS in dog plasma for pharmacokinetics of compound Danshen tablets SO JOURNAL OF CHROMATOGRAPHY B-ANALYTICAL TECHNOLOGIES IN THE BIOMEDICAL AND LIFE SCIENCES LA English DT Article DE Compound Danshen tablets; notoginsenoside R1; ginsenoside Rg1; ginsenoside Rb1; LC-MS/MS; Pharmacokinetics ID PERFORMANCE LIQUID-CHROMATOGRAPHY; TANDEM MASS-SPECTROMETRY; SOLID-PHASE EXTRACTION; 4 ACTIVE SAPONINS; RAT PLASMA; GINSENOSIDE RB-1; SHENMAI INJECTION; INTESTINAL BACTERIA; RB1; RG(1) AB Compound Danshen tablets are composed of Panax notoginseng, Salvia miltiorrhiza and Borneol. The tablets are prescribed for treatment of cardiovascular diseases in China. The present study aimed at developing a specific and sensitive LC-MS/MS method to simultaneously determine three bioactive P. notoginseng saponins, i.e., notoginsenoside R1. ginsenoside Rg1 and Rb1, in dogs after a single oral administration of the compound tablets in order to obtain the clinically relevant saponin-related pharmacodynamics of the tablets in patients. The R1, Rg1 and Rb1 were extracted from dog plasma with acetone-methanol (80:20, v/v), separated by reversed phase liquid chromatography and determined by tandem mass spectrometry (LC-MS/MS) with positive electrospray ionization (ESI). The developed method reached lower limit of quantitation (LLOQ) at 0.10 ng/ml for the three saponins. The method was validated in terms of selectivity, matrix effects, linearity, precision and accuracy, and then was applied to a pharmacokinetic study of the three bioactive saponins simultaneously in dogs after a single oral administration of compound Danshen tablets at a clinical equivalent dose. The C(max) and AUC((o-infinity)) for R1, Rg1 and Rb1 were 1.91, 3.34 and 28.6 ng/ml, and 7.5, 11.0, and 1712 (h ng/ml), respectively. (c) 2010 Elsevier ay. All rights reserved. C1 [Song, Min; Zhang, Siyun; Xu, Xiaoyan; Hang, Taijun] China Pharmaceut Univ, Dept Pharmaceut Anal, Nanjing 210009, Peoples R China. [Jia, Lee] NCI, Dev Therapeut Program, NIH, Rockville, MD 20852 USA. RP Song, M (reprint author), China Pharmaceut Univ, Dept Pharmaceut Anal, Nanjing 210009, Peoples R China. EM cqsongmin@yahoo.cn; zhangsiyun1984@hotmail.com; xiaoyan202003@yahoo.com.cn; hangtj@cpu.edu.cn; jiale@mail.nih.gov FU Ministry of Education of China [20090096120004]; China Postdoctoral Science Foundation [20070411039]; China Pharmaceutical University FX This research was supported by Doctoral Fund of Ministry of Education of China (20090096120004), China Postdoctoral Science Foundation (20070411039) and by special fund of China Pharmaceutical University. NR 46 TC 18 Z9 23 U1 9 U2 51 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 1570-0232 J9 J CHROMATOGR B JI J. Chromatogr. B PD DEC 15 PY 2010 VL 878 IS 32 BP 3331 EP 3337 DI 10.1016/j.jchromb.2010.10.007 PG 7 WC Biochemical Research Methods; Chemistry, Analytical SC Biochemistry & Molecular Biology; Chemistry GA 703CK UT WOS:000285951500001 PM 21081293 ER PT J AU Thornton, AM Shevach, EM AF Thornton, Angela M. Shevach, Ethan M. TI Response to Comment on "Expression of Helios, an Ikaros Transcription Factor Family Member, Differentiates Thymic-Derived from Peripherally Induced Foxp3(+) T Regulatory Cells" SO JOURNAL OF IMMUNOLOGY LA English DT Letter C1 [Shevach, Ethan M.] NIAID, Cellular Immunol Sect, Immunol Lab, NIH, Bethesda, MD 20892 USA. RP Shevach, EM (reprint author), NIAID, Cellular Immunol Sect, Immunol Lab, NIH, Bldg 10,Room 11N315, Bethesda, MD 20892 USA. EM eshevach@niaid.nih.gov NR 1 TC 1 Z9 1 U1 0 U2 2 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD DEC 15 PY 2010 VL 185 IS 12 BP 7129 EP 7130 DI 10.4049/jimmunol.1090106 PG 2 WC Immunology SC Immunology GA 688UF UT WOS:000284878700002 ER PT J AU Kinjyo, I Gordon, SM Intlekofer, AM Dowdell, K Mooney, EC Caricchio, R Grupp, SA Teachey, DT Rao, VK Lindsten, T Reiner, SL AF Kinjyo, Ichiko Gordon, Scott M. Intlekofer, Andrew M. Dowdell, Kennichi Mooney, Erin C. Caricchio, Roberto Grupp, Stephan A. Teachey, David T. Rao, V. Koneti Lindsten, Tullia Reiner, Steven L. TI Cutting Edge: Lymphoproliferation Caused by Fas Deficiency Is Dependent on the Transcription Factor Eomesodermin SO JOURNAL OF IMMUNOLOGY LA English DT Article ID CD8(+) T-CELLS; MICE; BET; HOMEOSTASIS; ELIMINATION; EFFECTOR AB A hallmark of autoimmune lymphoproliferative syndrome (ALPS), caused by mutation of the Fas death receptor, is massive lymphadenopathy from aberrant expansion of CD4(-)CD8(-) (double-negative [DN]) T cells. Eomesodermin (Eomes) is a member of the T-box family of transcription factors and plays critical roles in effector cell function and memory cell fitness of CD8(+) T lymphocytes. We provide evidence in this study that DN T cells exhibit dysregulated expression of Eomes in humans and mice with ALPS. We also find that T cell-specific deletion of Eomes prevents lymphoid hypertrophy and accumulation of DN T cells in Fas-mutant mice. Although Eomes has critical physiological roles in the function and homeostasis of CD8(+) T cells, overexpression of Eomes appears to enable pathological induction or expansion of unusual CD8-related T cell subsets. Thus, antagonism of Eomes emerges as a therapeutic target for DN T cell ablation in ALPS. The Journal of Immunology, 2010, 185: 7151-7155. C1 [Kinjyo, Ichiko; Gordon, Scott M.; Intlekofer, Andrew M.; Mooney, Erin C.; Lindsten, Tullia; Reiner, Steven L.] Univ Penn, Abramson Family Canc Res Inst, Philadelphia, PA 19104 USA. [Kinjyo, Ichiko; Gordon, Scott M.; Intlekofer, Andrew M.; Mooney, Erin C.; Reiner, Steven L.] Univ Penn, Div Infect Dis, Dept Med, Philadelphia, PA 19104 USA. [Grupp, Stephan A.; Teachey, David T.] Univ Penn, Dept Pediat, Philadelphia, PA 19104 USA. [Lindsten, Tullia] Univ Penn, Dept Pathol, Philadelphia, PA 19104 USA. [Dowdell, Kennichi; Rao, V. Koneti] NIAID, NIH, Bethesda, MD 20892 USA. [Caricchio, Roberto] Temple Univ, Div Rheumatol, Dept Med, Philadelphia, PA 19122 USA. [Grupp, Stephan A.; Teachey, David T.] Childrens Hosp, Dept Pediat, Philadelphia, PA 19104 USA. RP Reiner, SL (reprint author), Univ Penn, Abramson Family Canc Res Inst, 421 Curie Blvd,BRB 2-3,Room 414, Philadelphia, PA 19104 USA. EM sreiner@mail.med.upenn.edu FU National Institutes of Health [AI042370, AI076458, AI061699]; Abramson Family; Training Grant [T32 CA09140]; National Institutes of Health, National Institute of Allergy and Infectious Diseases, Bethesda, MD FX This work was supported by National Institutes of Health Grants AI042370, AI076458, and AI061699, the Abramson Family (to S. L. R.), and Training Grant T32 CA09140 (to S. M. G.). Part of this work was also supported by the Intramural Research Program of the National Institutes of Health, National Institute of Allergy and Infectious Diseases, Bethesda, MD. NR 24 TC 12 Z9 13 U1 0 U2 1 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD DEC 15 PY 2010 VL 185 IS 12 BP 7151 EP 7155 DI 10.4049/jimmunol.1003193 PG 5 WC Immunology SC Immunology GA 688UF UT WOS:000284878700008 PM 21076068 ER PT J AU Kannanganat, S Nigam, P Velu, V Earl, PL Lai, LL Chennareddi, L Lawson, B Wilson, RL Montefiori, DC Kozlowski, PA Moss, B Robinson, HL Amara, RR AF Kannanganat, Sunil Nigam, Pragati Velu, Vijayakumar Earl, Patricia L. Lai, Lilin Chennareddi, Lakshmi Lawson, Benton Wilson, Robert L. Montefiori, David C. Kozlowski, Pamela A. Moss, Bernard Robinson, Harriet L. Amara, Rama Rao TI Preexisting Vaccinia Virus Immunity Decreases SIV-Specific Cellular Immunity but Does Not Diminish Humoral Immunity and Efficacy of a DNA/MVA Vaccine SO JOURNAL OF IMMUNOLOGY LA English DT Article ID SIMIAN IMMUNODEFICIENCY VIRUS; CD4(+) T-CELLS; GM-CSF DNA; NEUTRALIZING ANTIBODIES; ADENOVIRUS VECTORS; GAG-POL; ENVELOPE GLYCOPROTEIN; MUCOSAL CHALLENGE; 89.6P CHALLENGE; RHESUS MACAQUES AB The influence of preexisting immunity to viral vectors is a major issue for the development of viral-vectored vaccines. In this study, we investigate the effect of preexisting vaccinia virus immunity on the immunogenicity and efficacy of a DNA/modified vaccinia Ankara (MVA) SIV vaccine in rhesus macaques using a pathogenic intrarectal SIV251 challenge. Preexisting immunity decreased SIV-specific CD8 and CD4 T cell responses but preserved the SIV-specific humoral immunity. In addition, preexisting immunity did not diminish the control of an SIV challenge mediated by the DNA/MVA vaccine. The peak and set point viremia was 150- and 17-fold lower, respectively, in preimmune animals compared with those of control animals. The peak and set point viremia correlated directly with colorectal virus at 2 wk postchallenge suggesting that early control of virus replication at the site of viral challenge was critical for viral control. Factors that correlated with early colorectal viral control included 1) the presence of anti-SIV IgA in rectal secretions, 2) high-avidity binding Ab for the native form of Env, and 3) low magnitude of vaccine-elicited SIV-specific CD4 T cells displaying the CCR5 viral coreceptor. The frequency of SIV-specific CD8 T cells in blood and colorectal tissue at 2 wk postchallenge did not correlate with early colorectal viral control. These results suggest that preexisting vaccinia virus immunity may not limit the potential of recombinant MVA vaccines to elicit humoral immunity and highlight the importance of immunodeficiency virus vaccines achieving early control at the mucosal sites of challenge. The Journal of Immunology, 2010, 185: 7262-7273. C1 [Kannanganat, Sunil; Nigam, Pragati; Velu, Vijayakumar; Lai, Lilin; Chennareddi, Lakshmi; Lawson, Benton; Robinson, Harriet L.; Amara, Rama Rao] Emory Univ, Dept Microbiol & Immunol, Vaccine Res Ctr, Yerkes Natl Primate Res Ctr, Atlanta, GA 30329 USA. [Earl, Patricia L.; Moss, Bernard] NIAID, Viral Dis Lab, NIH, Bethesda, MD 20892 USA. [Wilson, Robert L.; Kozlowski, Pamela A.] Louisiana State Univ, Hlth Sci Ctr, Gene Therapy Program, Dept Microbiol Immunol & Parasitol, New Orleans, LA 70112 USA. [Montefiori, David C.] Duke Univ, Med Ctr, Lab AIDS Vaccine Res & Dev, Dept Surg, Durham, NC 27710 USA. RP Amara, RR (reprint author), 954 Gatewood Rd, Atlanta, GA 30329 USA. EM ramara@emory.edu OI Velu, Vijayakumar/0000-0003-4238-1924 FU National Institute of Allergy and Infectious Diseases/National Institutes of Health [R01 AI057029, R01 AI071852]; Yerkes National Primate Research Center [P51 RR00165]; Emory Centers for AIDS [P30 AI050409]; National Institutes of Health [R24 RR16038] FX This work was supported by National Institute of Allergy and Infectious Diseases/National Institutes of Health Grants R01 AI057029 and R01 AI071852 (to R.R.A.), Yerkes National Primate Research Center Base Grant P51 RR00165, Emory Centers for AIDS Research Grant P30 AI050409, and National Institutes of Health Grant R24 RR16038 (to David I. Watkins). NR 60 TC 15 Z9 15 U1 0 U2 1 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD DEC 15 PY 2010 VL 185 IS 12 BP 7262 EP 7273 DI 10.4049/jimmunol.1000751 PG 12 WC Immunology SC Immunology GA 688UF UT WOS:000284878700022 PM 21076059 ER PT J AU Chinn, LW Tang, MZ Kessing, BD Lautenberger, JA Troyer, JL Malasky, MJ McIntosh, C Kirk, GD Wolinsky, SM Buchbinder, SP Gomperts, ED Goedert, JJ O'Brien, SJ AF Chinn, Leslie W. Tang, Minzhong Kessing, Bailey D. Lautenberger, James A. Troyer, Jennifer L. Malasky, Michael J. McIntosh, Carl Kirk, Gregory D. Wolinsky, Steven M. Buchbinder, Susan P. Gomperts, Edward D. Goedert, James J. O'Brien, Stephen J. TI Genetic Associations of Variants in Genes Encoding HIV-Dependency Factors Required for HIV-1 Infection SO JOURNAL OF INFECTIOUS DISEASES LA English DT Article ID IMMUNODEFICIENCY-VIRUS TYPE-1; GENOME-WIDE ASSOCIATION; INTERACTION DATABASE; PROTEIN; AIDS; REPLICATION; COMPLEX; IDENTIFICATION; RESTRICTION; PROGRESSION AB Background. High-throughput genome-wide techniques have facilitated the identification of previously unknown host proteins involved in cellular human immunodeficiency virus (HIV) infection. Recently, 3 independent studies have used small interfering RNA technology to silence each gene in the human genome to determine the importance of each in HIV infection. Genes conferring a significant effect were termed HIV-dependency factors (HDFs). Methods. We assembled high-density panels of 6380 single-nucleotide polymorphisms (SNPs) in 278 HDF genes and tested for genotype associations with HIV infection and AIDS progression in 1633 individuals from clinical AIDS cohorts. Results. After statistical correction for multiple tests, significant associations with HIV acquisition were found for SNPs in 2 genes, NCOR2 and IDH1. Weaker associations with AIDS progression were revealed for SNPs within the TM9SF2 and EGFR genes. Conclusions. This study independently verifies the influence of NCOR2 and IDH1 on HIV transmission, and its findings suggest that variation in these genes affects susceptibility to HIV infection in exposed individuals. C1 [Gomperts, Edward D.] Univ So Calif, Los Angeles, CA USA. [Gomperts, Edward D.] Childrens Hosp Los Angeles, Los Angeles, CA 90027 USA. [Buchbinder, Susan P.] San Francisco Dept Publ Hlth, San Francisco, CA USA. [Wolinsky, Steven M.] Northwestern Univ, Feinberg Sch Med, Chicago, IL 60611 USA. [Kirk, Gregory D.] Johns Hopkins Bloomberg Sch Publ Hlth, Baltimore, MD USA. [Goedert, James J.] NCI, Rockville, MD USA. [Kessing, Bailey D.; Troyer, Jennifer L.; Malasky, Michael J.] Sci Applicat Int Corp, Frederick, MD USA. [O'Brien, Stephen J.] NCI, Lab Genom Divers, Frederick, MD 21702 USA. RP O'Brien, SJ (reprint author), NCI, Lab Genom Divers, Frederick, MD 21702 USA. EM stephen.obrien@nih.gov RI Wolinsky, Steven/B-2893-2012; Troyer, Jennifer/B-8415-2012; OI Wolinsky, Steven/0000-0002-9625-6697 FU National Cancer Institute (NCI), National Institutes of Health (NIH) [HHSN261200800001E, N01-CO-12400]; NIH [R01-DA-04334, R01-DA-12568, UO1-AI-35042, 5-MO1-RR-00722, UO1-AI-35043, UO1-AI-37984, UO1-AI-35039, UO1-AI-35040, UO1-AI-37613, UO1-AI-35041, M01 RR00425]; NCI [UO1-AI-35042, 5-MO1-RR-00722, UO1-AI-35043, UO1-AI-37984, UO1-AI-35039, UO1-AI-35040, UO1-AI-37613, UO1-AI-35041, N02-CP-55504]; NIH, National Institute of Child Health and Human Development [1 R01 HD41224] FX Financial support: This project has been funded in whole or in part with federal funds from the National Cancer Institute (NCI), National Institutes of Health (NIH; contract HHSN261200800001E). AIDS Link to the Intravenous Experience was supported by NIH grants R01-DA-04334 and R01-DA-12568. Multicenter AIDS Cohort Study work was supported by NIH grants UO1-AI-35042, 5-MO1-RR-00722 (GCRC), UO1-AI-35043, UO1-AI-37984, UO1-AI-35039, UO1-AI-35040, UO1-AI-37613, UO1-AI-35041, and M01 RR00425 (National Center for Research Resources grant awarded to the GCRC at Harbor-University of California, Los Angeles, Research and Education Institute). The Multicenter Hemophilia Cohort Study is supported by NCI contract N02-CP-55504 with RTI International. The Hemophilia Growth and Development Study is funded by the NIH, National Institute of Child Health and Human Development, grant 1 R01 HD41224. NCI contracts include the following: UO1-AI-35042, 5-MO1-RR-00722 (GCRC), UO1-AI-35043, UO1-AI-37984, UO1-AI-35039, UO1-AI-35040, UO1-AI-37613, and UO1-AI-35041. This project has been funded in whole or in part with federal funds from the NCI, NIH, under contract N01-CO-12400. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 38 TC 11 Z9 11 U1 1 U2 2 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0022-1899 J9 J INFECT DIS JI J. Infect. Dis. PD DEC 15 PY 2010 VL 202 IS 12 BP 1836 EP 1845 DI 10.1086/657322 PG 10 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 681XC UT WOS:000284356300011 PM 21083371 ER PT J AU Li, M Cheung, GYC Hu, JH Wang, DC Joo, HS DeLeo, FR Otto, M AF Li, Min Cheung, Gordon Y. C. Hu, Jinhui Wang, Decheng Joo, Hwang-Soo DeLeo, Frank R. Otto, Michael TI Comparative Analysis of Virulence and Toxin Expression of Global Community-Associated Methicillin-Resistant Staphylococcus aureus Strains SO JOURNAL OF INFECTIOUS DISEASES LA English DT Article ID PANTON-VALENTINE LEUKOCIDIN; GENE-EXPRESSION; POLYMORPHONUCLEAR LEUKOCYTES; SKIN INFECTIONS; PNEUMONIA; EVOLUTION; DISEASE; USA300; MRSA; AGR AB The current pandemic of community-associated methicillin-resistant Staphylococcus aureus (CA-MRSA) skin infections is caused by several genetically unrelated clones. Here, we analyzed virulence of globally occurring CA-MRSA strains in a rabbit skin infection model. We used rabbits because neutrophils from this animal species have relatively high sensitivity to Panton-Valentine leukocidin (PVL), a toxin epidemiologically correlated with many CA-MRSA infections. Virulence in the rabbit model correlated with in vitro neutrophil lysis and transcript levels of phenol-soluble modulin a and a-toxin, but not PVL genes. Furthermore, abscesses caused by USA300 and its PVL-negative progenitor USA500 were comparatively large and similar in size, suggesting that PVL has played a limited role in the evolution of USA300 virulence in the context of skin infections. Our study indicates a major but not exclusive impact of virulence on the epidemiological success of USA300 and other CA-MRSA strains and emphasizes the importance of core genome-encoded toxins in CA-MRSA skin infections. C1 [Otto, Michael] NIAID, Lab Human Bacterial Pathogenesis, NIH, Bethesda, MD 20892 USA. [Li, Min; Hu, Jinhui] Huashan Hosp, Dept Lab Med, Shanghai 200040, Peoples R China. [Wang, Decheng; Joo, Hwang-Soo] Fudan Univ, Shanghai Med Coll, Key Lab Med Mol Virol, Inst Med Microbiol, Shanghai 200433, Peoples R China. [Wang, Decheng; Joo, Hwang-Soo] Fudan Univ, Shanghai Med Coll, Inst Biomed Sci, Shanghai 200433, Peoples R China. [DeLeo, Frank R.] NIAID, Rocky Mt Labs, NIH, Hamilton, MT 59840 USA. RP Otto, M (reprint author), NIAID, Lab Human Bacterial Pathogenesis, NIH, Bldg 33,1W10,9000 Rockville Pike, Bethesda, MD 20892 USA. EM ruth_limin124@yahoo.com; motto@niaid.nih.gov RI Cheung, Yiu Chong /K-3565-2012; OI JOO, HWANG-SOO/0000-0003-4668-3225; DeLeo, Frank/0000-0003-3150-2516; Otto, Michael/0000-0002-2222-4115 FU National Institute of Allergy and Infectious Diseases, National Institutes of Health; National Natural Science Foundation of China; Shanghai Pujiang Program [09PJ1402300] FX Financial support: This work was supported by the Intramural Research Program of the National Institute of Allergy and Infectious Diseases, National Institutes of Health (to M.O. and F. R. D.), the National Natural Science Foundation of China (grant 30900026 to M. L.), and the Shanghai Pujiang Program (grant 09PJ1402300 to M.L.). NR 44 TC 99 Z9 100 U1 1 U2 11 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0022-1899 J9 J INFECT DIS JI J. Infect. Dis. PD DEC 15 PY 2010 VL 202 IS 12 BP 1866 EP 1876 DI 10.1086/657419 PG 11 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 681XC UT WOS:000284356300014 PM 21050125 ER PT J AU Sweeney, DA Cui, XZ Solomon, SB Vitberg, DA Migone, TS Scher, D Danner, RL Natanson, C Subramanian, GM Eichacker, PQ AF Sweeney, Daniel A. Cui, Xizhong Solomon, Steven B. Vitberg, David A. Migone, Thi S. Scher, Dara Danner, Robert L. Natanson, Charles Subramanian, G. Mani Eichacker, Peter Q. TI Anthrax Lethal and Edema Toxins Produce Different Patterns of Cardiovascular and Renal Dysfunction and Synergistically Decrease Survival in Canines SO JOURNAL OF INFECTIOUS DISEASES LA English DT Article ID BACILLUS-ANTHRACIS; CYCLIC-AMP; ESCHERICHIA-COLI; INHALATIONAL ANTHRAX; PROTECTIVE ANTIGEN; CHOLERA TOXIN; SEPTIC SHOCK; DOWN METHOD; RAT MODEL; IN-VIVO AB Background. High mortality in the 2001 US and recent European anthrax outbreaks suggests that better understanding of the effects of the toxins produced by this bacterium is needed to improve treatment. Methods and results. Here, 24-h edema (ETx) and lethal (LeTx) toxin infusions were investigated for 96 h in sedated canines receiving mechanical ventilation. The initial study compared similarly lethal doses of ETx (n = 8) or LeTx (n = 15) alone. ETx was 24 times less lethal than LeTx, and the median time to death in nonsurvivors (n = 6 and n = 9, respectively) was shorter with ETx (42 vs 67 h; P = .04). Compared with controls (n = 9), both toxins decreased arterial and central venous pressures and systemic vascular resistance and increased heart rate, cardiac index, blood urea nitrogen (BUN) level, creatinine (Cr) concentration, BUN: Cr ratio, and hepatic transaminase levels (P <= .05 for toxin effect or time interaction). However, ETx stimulated early diuresis, reduced serum sodium levels, and had more pronounced vasodilatory effects, compared with LeTx, as reflected by greater or earlier central venous pressures, systemic vascular resistance, and changes in the BUN: Cr ratio (P <= .01). LeTx progressively decreased the left ventricular ejection fraction (P <= .002). In a subsequent study, a lethal dose of LeTx with an equimolar nonlethal ETx dose (n = 8) increased mortality, compared with LeTx alone (n = 8; P = .05). Conclusion. Shock with ETx or LeTx may require differing supportive therapies, whereas toxin antagonists should likely target both toxins. C1 [Sweeney, Daniel A.; Cui, Xizhong; Solomon, Steven B.; Vitberg, David A.; Scher, Dara; Danner, Robert L.; Natanson, Charles; Eichacker, Peter Q.] NIH, Dept Crit Care Med, Ctr Clin, Bethesda, MD 20892 USA. [Migone, Thi S.; Subramanian, G. Mani] Human Genome Sci, Rockville, MD USA. RP Eichacker, PQ (reprint author), NIH, Dept Crit Care Med, Ctr Clin, Bldg 10,Rm 2C145, Bethesda, MD 20892 USA. EM peichacker@mail.cc.nih.gov FU National Institutes of Health (NIH) Clinical Center; Trans NIH-Food and Drug Administration Biodefense FX Financial support: National Institutes of Health (NIH) Clinical Center; Trans NIH-Food and Drug Administration Biodefense grant. NR 46 TC 28 Z9 28 U1 0 U2 4 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0022-1899 J9 J INFECT DIS JI J. Infect. Dis. PD DEC 15 PY 2010 VL 202 IS 12 BP 1885 EP 1896 DI 10.1086/657408 PG 12 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 681XC UT WOS:000284356300016 PM 21067373 ER PT J AU Brotman, RM Klebanoff, MA Nansel, TR Yu, KF Andrews, WW Zhang, J Schwebke, JR AF Brotman, Rebecca M. Klebanoff, Mark A. Nansel, Tonja R. Yu, Kai F. Andrews, William W. Zhang, Jun Schwebke, Jane R. TI Bacterial Vaginosis Assessed by Gram Stain and Diminished Colonization Resistance to Incident Gonococcal, Chlamydial, and Trichomonal Genital Infection SO JOURNAL OF INFECTIOUS DISEASES LA English DT Article ID SEXUALLY-TRANSMITTED-DISEASES; IMMUNODEFICIENCY-VIRUS TYPE-1; REPORTED CONDOM USE; VAGINAL FLORA; TRACT-INFECTIONS; IN-VITRO; WOMEN; ASSOCIATION; ACQUISITION; HIV AB Background. We sought to assess the relationship between bacterial vaginosis (BV) assessed by Gram stain and incident trichomonal, gonococcal, and/or chlamydial genital infection. Methods. This longitudinal study included 3620 nonpregnant women aged 15-44 years who presented for routine care at 12 clinics in Birmingham, Alabama. Participants were assessed quarterly for 1 year. Vaginal smears were categorized by the Nugent Gram stain score (0 3, normal; 4 6, intermediate state; 7 10, BV). Pooled logistic regression was used to estimate the hazard ratios for the comparison of trichomonal, gonococcal, and chlamydial infection incidence in participants by Nugent score at the prior visit. Participants were censored at their first visit with a positive test result for trichomonal, gonococcal, and/or chlamydial infection. Results. Of the 10,606 eligible visits, 37.96% were classified by BV and 13.3% by positive detection of trichomonal, gonococcal, and/or chlamydial infection. An intermediate state or BV at the prior visit was associated with a 1.5-2-fold increased risk for incident trichomonal, gonococcal, and/or chlamydial infection (adjusted hazard ratio [AHR] for intermediate state, 1.41 [95% confidence interval {CI}, 1.12-1.76]; AHR for BV, 1.73 [95% CI, 1.42-2.11]; Pp. 058 for trend). Estimates were similar for trichomonal-only, gonococcal-only, and chlamydial-only infection outcomes. Conclusion. BV microbiota as gauged by Gram stain is associated with a significantly elevated risk for acquisition of trichomonal, gonococcal, and/or chlamydial genital infection. C1 [Brotman, Rebecca M.] Univ Maryland, Sch Med, Inst Genome Sci, Dept Epidemiol & Publ Hlth, Baltimore, MD 21201 USA. [Klebanoff, Mark A.; Nansel, Tonja R.; Yu, Kai F.; Zhang, Jun] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Div Epidemiol Stat & Prevent Res, NIH, US Dept HHS, Bethesda, MD USA. [Andrews, William W.] Univ Alabama, Dept Obstet & Gynecol, Birmingham, AL 35294 USA. [Schwebke, Jane R.] Univ Alabama, Dept Med, Birmingham, AL 35294 USA. RP Brotman, RM (reprint author), Univ Maryland, Sch Med, Inst Genome Sci, Dept Epidemiol & Publ Hlth, BioPk Bldg 2,801 W Baltimore St,Room 633, Baltimore, MD 21201 USA. EM rbrotman@som.umaryland.edu RI Brotman, Rebecca/H-5442-2011; OI Brotman, Rebecca/0000-0001-8762-6214; Nansel, Tonja/0000-0002-8298-7595 FU National Institute of Allergy and Infectious Diseases [K01-AI080974]; Eunice Kennedy Shriver National Institute of Child Health and Human Development [NO-1-HD-8-3293, Z01 HD002535-10] FX Financial support: National Institute of Allergy and Infectious Diseases (grant K01-AI080974); Eunice Kennedy Shriver National Institute of Child Health and Human Development (contract NO-1-HD-8-3293 and intramural fund Z01 HD002535-10). NR 50 TC 89 Z9 91 U1 1 U2 7 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0022-1899 J9 J INFECT DIS JI J. Infect. Dis. PD DEC 15 PY 2010 VL 202 IS 12 BP 1907 EP 1915 DI 10.1086/657320 PG 9 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 681XC UT WOS:000284356300018 PM 21067371 ER PT J AU Kutty, G Achaz, G Maldarelli, F Varma, A Shroff, R Becker, S Fantoni, G Kovacs, JA AF Kutty, Geetha Achaz, Guillaume Maldarelli, Frank Varma, Ashok Shroff, Robert Becker, Steven Fantoni, Giovanna Kovacs, Joseph A. TI Characterization of the Meiosis-Specific Recombinase Dmc1 of Pneumocystis SO JOURNAL OF INFECTIOUS DISEASES LA English DT Article ID MAJOR SURFACE GLYCOPROTEIN; CARINII DIHYDROPTEROATE SYNTHASE; EXPRESSION SITE; MEIOTIC RECOMBINATION; DIHYDROFOLATE-REDUCTASE; PHEROMONE RECEPTOR; GENETIC DIVERSITY; MUTATIONS; HUMANS; RAD51 AB The life cycle of Pneumocystis, which causes life-threatening pneumonia in immunosuppressed patients, remains poorly defined. In the present study, we have identified and characterized an orthologue of dmc1, a gene specific for meiotic recombination in yeast, in 3 species of Pneumocystis. dmc1 is a single-copy gene that is transcribed as similar to 1.2-kb messenger RNA, which encodes a protein of 336-337 amino acids. Pneumocystis Dmc1 was 61%-70% identical to those from yeast. Confocal microscopy results indicated that the expression of Dmc1 is primarily confined to the cyst form of Pneumocystis. By sequence analysis of 2 single-copy regions of the human Pneumocystis jirovecii genome, we can infer multiple recombination events, which are consistent with meiotic recombination in this primarily haploid organism. Taken together, these studies support the occurrence of a sexual phase in the life cycle of Pneumocystis. C1 [Achaz, Guillaume] Univ Paris 06, Paris, France. [Maldarelli, Frank] NCI, HIV Drug Resistance Program, NIH, Frederick, MD 21701 USA. [Achaz, Guillaume] Unite Mixte Rech 7138 & Atelier Bioinformat, Paris, France. [Shroff, Robert] NCI, Biochem & Mol Biol Lab, NIH, Bethesda, MD 20892 USA. [Kutty, Geetha; Fantoni, Giovanna; Kovacs, Joseph A.] NIAID, Dept Crit Care Med, NIH, Ctr Clin, Bethesda, MD 20892 USA. [Varma, Ashok] NIAID, Lab Clin Infect Dis, Bethesda, MD 20892 USA. [Becker, Steven] NIAID, Biol Imaging Facil, Bethesda, MD 20892 USA. RP Kovacs, JA (reprint author), Bldg 10,Room 2C145,MSC 1662, Bethesda, MD 20892 USA. EM jkovacs@nih.gov FU National Institutes of Health Clinical Center; National Institute of Allergy and Infectious Diseases; National Cancer Institute FX Financial support: This research was supported by the Intramural Research Programs of the National Institutes of Health Clinical Center, the National Institute of Allergy and Infectious Diseases, and the National Cancer Institute. NR 50 TC 4 Z9 4 U1 0 U2 1 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0022-1899 J9 J INFECT DIS JI J. Infect. Dis. PD DEC 15 PY 2010 VL 202 IS 12 BP 1920 EP 1929 DI 10.1086/657414 PG 10 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 681XC UT WOS:000284356300020 PM 21050123 ER PT J AU Xue, L Wu, LG AF Xue, Lei Wu, Ling-Gang TI Post-tetanic potentiation is caused by two signalling mechanisms affecting quantal size and quantal content SO JOURNAL OF PHYSIOLOGY-LONDON LA English DT Article ID TERM SYNAPTIC PLASTICITY; READILY RELEASABLE POOL; HELD SYNAPSE; RAT CALYX; EVOKED NEUROTRANSMISSION; GLUTAMATE RECEPTORS; CA2+ CHANNELS; VESICLES; DEPRESSION; TRANSMISSION AB A high-frequency action potential train induces post-tetanic potentiation (PTP) of transmission at many synapses by increasing the intra-terminal calcium concentration, which may increase the quantal content by activation of protein kinase C (PKC). A recent study found that an increase of the mEPSC size, caused by compound vesicle fusion, parallels PTP, suggesting that the quantal size increase also contributes to the PTP generation. However, the strength of this suggestion is somewhat undermined by recent studies suggesting that vesicles responsible for spontaneous and evoked EPSCs may originate from different pools. Furthermore, it is unclear whether the quantal size increase is also mediated by PKC. The present work addressed these issues at a large calyx of Held synapse. We found that PTP was caused by both a PKC-dependent increase of the quantal content and a PKC-independent increase of the quantal size. In addition, we found that mEPSCs and EPSCs were subjected to similar up- and down-regulation, which verifies the basic assumption of quantal analysis - the same mechanism controls the quantal size of spontaneous and evoked release. This verification supports the use of quantal analysis at central synapses. However, unlike the traditional quantal analysis that attributes the quantal size change to a postsynaptic mechanism, the present work, together with one of our previous studies, suggests that the quantal size increase is caused by a presynaptic mechanism, the compound fusion among vesicles that forms large compound vesicles. C1 [Xue, Lei; Wu, Ling-Gang] NINDS, Bethesda, MD 20892 USA. RP Wu, LG (reprint author), NINDS, 35 Convent Dr,Bldg 35, Bethesda, MD 20892 USA. EM wul@ninds.nih.gov FU National Institute of Neurological Disorders and Stroke FX We thank Drs Liming He and Fujun Luo for comments on the manuscript. This work was supported by the National Institute of Neurological Disorders and Stroke Intramural Research Program. NR 35 TC 15 Z9 15 U1 1 U2 6 PU WILEY-BLACKWELL PUBLISHING, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0022-3751 J9 J PHYSIOL-LONDON JI J. Physiol.-London PD DEC 15 PY 2010 VL 588 IS 24 BP 4987 EP 4994 DI 10.1113/jphysiol.2010.196964 PG 8 WC Neurosciences; Physiology SC Neurosciences & Neurology; Physiology GA 695HG UT WOS:000285360600014 PM 21041528 ER PT J AU Chandran, PL Dimitriadis, EK Basser, PJ Horkay, F AF Chandran, Preethi L. Dimitriadis, Emilios K. Basser, Peter J. Horkay, Ferenc TI Probing Interactions between Aggrecan and Mica Surface by the Atomic Force Microscopy SO JOURNAL OF POLYMER SCIENCE PART B-POLYMER PHYSICS LA English DT Article DE adsorption; aggrecan; atomic force microscopy; osmotic pressure ID CONNECTIVE-TISSUE POLYSACCHARIDES; PHYSIOLOGICAL SALT-SOLUTIONS; CARTILAGE AGGRECAN; ARTICULAR-CARTILAGE; MACROMOLECULES; PROTEOGLYCAN; CALCIFICATION; NANOMECHANICS; PROTEIN; DNA AB Aggrecan is a bottlebrush shaped macromolecule found in the extracellular matrix of cartilage. The negatively charged glycosaminoglycan (GAG) chains attached to its protein backbone give aggrecan molecules a high charge density, which is essential for exerting high osmotic swelling pressure and resisting compression under external load. In solution, aggrecan assemblies are insensitive to the presence of calcium ions, and show distinct osmotic pressure versus concentration regimes. The aim of this study is to investigate the effect of ionic environment on the structure of aggrecan molecules adsorbed onto well-controlled mica surfaces. The conformation of the aggrecan was visualized using Atomic Force Microscopy. On positively charged APS mica the GAG chains of the aggrecan molecules are distinguishable, and their average dimensions are practically unaffected by the presence of salt ions. With increasing aggrecan concentration they form clusters, and at higher concentrations they form a continuous monolayer of conforming molecules. On negatively charged mica, the extent of aggrecan adsorption varies with salt composition. Understanding aggrecan adsorption onto a charged surface provides insight into its interactions with bone and implant surfaces in the biological milieu. (C) 2010 Wiley Periodicals, Inc.dagger J Polym Sci Part B: Polym Phys 48: 2575-2581, 2010 C1 [Chandran, Preethi L.; Basser, Peter J.; Horkay, Ferenc] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Sect Tissue Biophys & Biomimet, Program Pediat Imaging & Tissue Sci, NIH, Bethesda, MD 20892 USA. [Chandran, Preethi L.; Dimitriadis, Emilios K.] Natl Inst Biomed Imaging & Bioengn, Lab Bioengn & Phys Sci, NIH, Bethesda, MD 20892 USA. RP Chandran, PL (reprint author), Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Sect Tissue Biophys & Biomimet, Program Pediat Imaging & Tissue Sci, NIH, Bethesda, MD 20892 USA. EM chandranlp@mail.nih.gov; horkay@helix.nih.gov RI Basser, Peter/H-5477-2011 FU NIH, NICHD FX This work was supported by the Intramural Research Program of the NIH, NICHD. NR 33 TC 2 Z9 2 U1 1 U2 4 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0887-6266 J9 J POLYM SCI POL PHYS JI J. Polym. Sci. Pt. B-Polym. Phys. PD DEC 15 PY 2010 VL 48 IS 24 BP 2575 EP 2581 DI 10.1002/polb.22132 PG 7 WC Polymer Science SC Polymer Science GA 680JN UT WOS:000284228300010 PM 22473175 ER PT J AU Zheng, YL Hu, YF Zhang, AP Wang, W Li, B Amin, N Grant, P Pant, HC AF Zheng, Ya-Li Hu, Ya-Fang Zhang, AiPing Wang, Wei Li, Bo Amin, Niranjana Grant, Philip Pant, Harish C. TI Overexpression of p35 in Min6 pancreatic beta cells induces a stressed neuron-like apoptosis SO JOURNAL OF THE NEUROLOGICAL SCIENCES LA English DT Article; Proceedings Paper CT 1st Congress on Vascular Dementia (VaD) CY 2009 CL Geneva, SWITZERLAND DE Cdk5 activity; p35; Pancreatic beta cells; Insulin secretion ID DEPENDENT KINASE-5 ACTIVITY; ALZHEIMERS-DISEASE; DIABETES-MELLITUS; INSULIN-SECRETION; CDK5 ACTIVITY; ACTIVATOR; GLUCOSE; EXPRESSION; P25; PHOSPHORYLATION AB Cdk5 activity has been implicated in brain development and the regulation of many neuronal processes. Recently, the expression of p35 and Cdk5 activity has been reported in pancreatic beta cells. Decreased Cdk5 activity enhanced glucose-stimulated insulin secretion. This suggests that Cdk5 may play an important role in the regulation of insulin secretion. To further understand how Cdk5 regulates insulin secretion in glucose-stimulated pancreatic beta cells, we first confirmed the presence of a low level of p35 in pancreatic Min6 cells. Next, in a time-course experiment in high glucose (25 mM) we showed that endogenous p35 increased gradually accompanied by a 3-fold increase in Cdk5 activity by 16 h. Insulin secretion, however, doubled after 2 h followed by progressive downregulation, negatively correlated with Cdk5 activity. On the other hand, overexpression of p35 in these cells resulted in more than a three-fold increase in Cdk5 activity within 2 h coupled to a 50% reduction in insulin secretion in both high and low (3 mM) glucose. Most significantly, cells overexpressing p35, treated with high glucose for 4 h, showed induction of p25, the p35-derived truncated fragment which hyperactivates Cdk5 in neurons. As a result, insulin secretion was inhibited and cells became apoptotic. Roscovitine or co-infection of dominant negative Cdk5 (dnCdk5) with p35 increased insulin secretion and inhibited apoptosis. These results suggest that the model for deregulation and hyperactivation of Cdk5 in neurodegeneration may apply to the pathology seen in type 2 diabetes (T2DM). It is consistent with the view that Alzheimer's disease and T2DM are linked metabolically and pathologically by Cdk5 in a number of ways. (C) 2010 Published by Elsevier B.V. C1 [Zheng, Ya-Li; Wang, Wei; Li, Bo] Peoples Hosp Ningxia Prov, Dept Nephrol, Yinchuan 750021, Ningxia Prov, Peoples R China. [Zheng, Ya-Li; Amin, Niranjana; Grant, Philip; Pant, Harish C.] NINDS, Lab Neurochem LNC, NIH, Bethesda, MD 20892 USA. [Hu, Ya-Fang; Zhang, AiPing] NIDCR, OIIB, NIH, Bethesda, MD 20892 USA. RP Zheng, YL (reprint author), Ningxia Peoples Hosp, Dept Nephrol, Yinchuan 750021, Ningxia Prov, Peoples R China. EM yalinew@yahoo.com FU Intramural NIH HHS NR 31 TC 8 Z9 8 U1 0 U2 2 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0022-510X J9 J NEUROL SCI JI J. Neurol. Sci. PD DEC 15 PY 2010 VL 299 IS 1-2 SI SI BP 101 EP 107 DI 10.1016/j.jns.2010.08.067 PG 7 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 705JC UT WOS:000286123700023 PM 20926102 ER PT J AU Emerman, AB Zhang, ZR Chakrabarti, O Hegde, RS AF Emerman, Amy B. Zhang, Zai-Rong Chakrabarti, Oishee Hegde, Ramanujan S. TI Compartment-Restricted Biotinylation Reveals Novel Features of Prion Protein Metabolism in Vivo SO MOLECULAR BIOLOGY OF THE CELL LA English DT Article ID SIGNAL RECOGNITION PARTICLE; SINGLE TRANSLATION PRODUCT; IRON-SULFUR CLUSTER; ENDOPLASMIC-RETICULUM; TRANSMEMBRANE FORM; GLUCOCORTICOID-RECEPTOR; REGULATED EXPRESSION; NASCENT PREPROLACTIN; MAMMALIAN-CELLS; MITOCHONDRIAL AB Proteins are often made in more than one form, with alternate versions sometimes residing in different cellular compartments than the primary species. The mammalian prion protein (PrP), a cell surface GPI-anchored protein, is a particularly noteworthy example for which minor cytosolic and transmembrane forms have been implicated in disease pathogenesis. To study these minor species, we used a selective labeling strategy in which spatially restricted expression of a biotinylating enzyme was combined with asymmetric engineering of the cognate acceptor sequence into PrP. Using this method, we could show that even wild-type PrP generates small amounts of the (Ctm)PrP transmembrane form. Selective detection of (Ctm)PrP allowed us to reveal its N-terminal processing, long half-life, residence in both intracellular and cell surface locations, and eventual degradation in the lysosome. Surprisingly, some human disease-causing mutants in PrP selectively stabilized (Ctm)PrP, revealing a previously unanticipated mechanism of (Ctm)PrP up-regulation that may contribute to disease. Thus, spatiotemporal tagging has uncovered novel aspects of normal and mutant PrP metabolism and should be readily applicable to the analysis of minor topologic isoforms of other proteins. C1 [Emerman, Amy B.; Zhang, Zai-Rong; Chakrabarti, Oishee; Hegde, Ramanujan S.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Cell Biol & Metab Program, NIH, Bethesda, MD 20892 USA. RP Hegde, RS (reprint author), Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Cell Biol & Metab Program, NIH, Bethesda, MD 20892 USA. EM hegder@mail.nih.gov RI Zhang, Zairong/G-1030-2013; OI Hegde, Ramanujan/0000-0001-8338-852X FU National Institute of Child Health and Human Development at the National Institutes of Health FX We thank members of the Hegde Lab, particularly Aarthi Ashok, for useful discussions. This work was supported by the Intramural Research Program of the National Institute of Child Health and Human Development at the National Institutes of Health. NR 62 TC 18 Z9 19 U1 0 U2 6 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 J9 MOL BIOL CELL JI Mol. Biol. Cell PD DEC 15 PY 2010 VL 21 IS 24 BP 4325 EP 4337 DI 10.1091/mbc.E10-09-0742 PG 13 WC Cell Biology SC Cell Biology GA 695AP UT WOS:000285343300004 PM 20980618 ER PT J AU Herath, P Gallea, C van der Veen, JW Horovitz, SG Hallett, M AF Herath, Priyantha Gallea, Cecile van der Veen, Jan Willem Horovitz, Silvina G. Hallett, Mark TI In Vivo Neurochemistry of Primary Focal Hand Dystonia: A Magnetic Resonance Spectroscopic Neurometabolite Profiling Study at 3T SO MOVEMENT DISORDERS LA English DT Article DE dystonia; magnetic resonance spectroscopy; gamma amino butyric acid (GABA); metabolic profile; imaging ID HUMAN BRAIN; SURROUND INHIBITION; PREMOTOR CORTEX; GABA; SPECTRA; MOTOR; NEUROTRANSMITTER; PATHOPHYSIOLOGY; METABOLITES; GLUTAMATE AB The neurochemical basis of dystonia is unknown. The purpose of this study was to assess the differences of the inhibitory neurotransmitter, gamma amino butyric acid (GABA), in the sensorimotor cortex and the basal ganglia using magnetic resonance spectroscopy with optimized GABA sensitivity. Twenty-two patients with focal hand dystonia and 22 healthy controls were studied. No significant differences in GABA were observed between the groups in either the sensorimotor cortex or in the basal ganglia. (C) 2010 Movement Disorder Society C1 [Herath, Priyantha; Gallea, Cecile; Horovitz, Silvina G.; Hallett, Mark] NINDS, Med Neurol Branch, Human Motor Control Sect, NIH, Bethesda, MD 20892 USA. [van der Veen, Jan Willem] NIMH, MRS Core Facil, NIH, Bethesda, MD 20892 USA. RP Herath, P (reprint author), NINDS, Med Neurol Branch, Human Motor Control Sect, NIH, Bldg 10, Bethesda, MD 20892 USA. EM herapx@gmail.com FU NIH through US federal government; NINDS; US Army; Ariston Pharmaceuticals; Kinetics Foundation; NIH FX Alan Barnet helped us with the algorithm that we used for segmenting the voxels into white matter and grey matter compartments. This work was carried out with intramural funding from the NIH- available through US federal government funds. None of the authors have received, or are expected to receive any other funding.; All funding for the work are from the NINDS intramural budget. Dr. Hallett reports: Consulting and Advisory Board Membership with honoraria: Neurotoxin Institute; Grants/Research: Funding from NIH, the US Army, Ariston Pharmaceuticals, Kinetics Foundation; Honoraria: University of Navarra, State of New York, University of Wisconsin, Massachusetts Medical Society, Parkinson and Aging Research Society, Columbia University; Intellectual Property Rights: H-coil; Royalties: Wiley-Blackwell, Oxford University Press, Lippincott, Wilkins and Williams, Cambridge University Press, Elsevier Publishers, Springer. NR 31 TC 9 Z9 10 U1 0 U2 1 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0885-3185 J9 MOVEMENT DISORD JI Mov. Disord. PD DEC 15 PY 2010 VL 25 IS 16 BP 2800 EP 2808 DI 10.1002/mds.23306 PG 9 WC Clinical Neurology SC Neurosciences & Neurology GA 703LK UT WOS:000285979200015 PM 20979122 ER PT J AU Carol, H Morton, CL Gorlick, R Kolb, EA Keir, ST Reynolds, CP Kang, MH Maris, JM Billups, C Smith, MA Houghton, PJ Lock, RB AF Carol, Hernan Morton, Christopher L. Gorlick, Richard Kolb, E. Anders Keir, Stephen T. Reynolds, C. Patrick Kang, Min H. Maris, John M. Billups, Catherine Smith, Malcolm A. Houghton, Peter J. Lock, Richard B. TI Initial Testing (Stage 1) of the Akt Inhibitor GSK690693 by the Pediatric Preclinical Testing Program SO PEDIATRIC BLOOD & CANCER LA English DT Article DE Akt inhibitor; developmental therapeutics; preclinical testing ID ACUTE LYMPHOBLASTIC-LEUKEMIA; HUMAN NEUROBLASTOMA-CELLS; GROWTH-FACTOR; IN-VIVO; ANTITUMOR-ACTIVITY; KINASE INHIBITOR; 3-KINASE PATHWAY; CANCER MODELS; CHEMOTHERAPY; ACTIVATION AB Background GSK690693 is a small molecule ATP competitive inhibitor of the pro survival kinase Akt Since Akt regulates multiple downstream targets including transcription factors, glycogen synthase 3 the pro apoptotic protein Bid is well as MDM2 and mTORC1, it was tested against the in vitro and in vivo panels of the Pediatric Preclinical Testing Program (PPTP) Procedures GSK690693 was tested in vitro at concentrations from 1 nM to 10 mu M and against the in vivo panel of xenografts at a dose of 30 mg/kg daily x 5 for 6 consecutive weeks Three measures of in vivo antitumor activity were used (1) an objective response measure modeled after the clinical setting (2) a treated to control (TIC) tumor volume measure and (3) a time to event measure based on the median event free survival (EFS) of treated and control animals for each xenograft Results GSK690693 inhibited cell growth in vitro with IC(50) values between 6 5 nM and >10 mu M In vivo GSK690693 significantly increased EFS in 11 of 34 (32%) solid tumor xenografts most notably in all 6 osteosarcoma models but not in any of the 8 ALL xenografts tested No objective responses were observed and only one solid tumor met EFS TIC criteria for intermediate activity Conclusions GSK690693 demonstrated broad activity in vitro, how ever our results against both the solid tumor and ALL PPTP in vivo panels demonstrate that, as single agent at the dose and schedule used GSK690693 has only modest antitumor activity Pediatr Blood Cancer 2010 55 1329-1337 (C) 2010 Wiley Liss Inc C1 [Lock, Richard B.] Lowy Canc Res Ctr, Childrens Canc Inst Australia Med Res, Randwick, NSW 2031, Australia. [Morton, Christopher L.; Billups, Catherine] St Jude Childrens Hosp, Memphis, TN 38105 USA. [Gorlick, Richard] Childrens Hosp Montefiore, Bronx, NY USA. [Kolb, E. Anders] Alfred I DuPont Hosp Children, Wilmington, DE USA. [Keir, Stephen T.] Duke Univ, Med Ctr, Durham, NC USA. [Reynolds, C. Patrick; Kang, Min H.] Texas Tech Univ, Hlth Sci Ctr, Lubbock, TX 79430 USA. [Maris, John M.] Univ Penn, Childrens Hosp Philadelphia, Sch Med, Philadelphia, PA 19104 USA. [Maris, John M.] Abramson Family Canc Res Inst, Philadelphia, PA USA. [Smith, Malcolm A.] NCI, Canc Therapy Evaluat Program, Bethesda, MD 20892 USA. [Houghton, Peter J.] Nationwide Childrens Hosp, Columbus, OH USA. RP Lock, RB (reprint author), Lowy Canc Res Ctr, Childrens Canc Inst Australia Med Res, Randwick, NSW 2031, Australia. RI Houghton, Peter/E-3265-2011; Carol, Hernan/F-5750-2013; Lock, Richard/G-4253-2013; OI Carol, Hernan/0000-0002-9443-8032; Reynolds, C. Patrick/0000-0002-2827-8536 FU National Cancer Institute [NO1-CM-42216, CA21765, CA108786] FX This work was supported by NO1-CM-42216, CA21765 and CA108786 from the National Cancer Institute and used GSK690693 supplied by GlaxoSmithKline In addition to the authors this study represents work contributed by the following Sherry Ansher Catherine A Billups Ingrid Boehm Joshua Courtright Mila Dolotin Edward Favours, Henry S Friedman Debbie Payne-Turner Charles Stopford Chandra Tucker, Amy E Watkins Joe Zeidner, Ellen Zhang and Jian Zhang Children s Cancer Institute Australia for Medical Research is affiliated with the University of New South Wales and Sydney Children s Hospital NR 37 TC 25 Z9 25 U1 0 U2 5 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 1545-5009 J9 PEDIATR BLOOD CANCER JI Pediatr. Blood Cancer PD DEC 15 PY 2010 VL 55 IS 7 BP 1329 EP 1337 DI 10.1002/pbc.22710 PG 9 WC Oncology; Hematology; Pediatrics SC Oncology; Hematology; Pediatrics GA 677WB UT WOS:000284023600015 PM 20740623 ER PT J AU Dauvillee, D Delhaye, S Gruyer, S Slomianny, C Moretz, SE d'Hulst, C Long, CA Ball, SG Tomavo, S AF Dauvillee, David Delhaye, Stephane Gruyer, Sebastien Slomianny, Christian Moretz, Samuel E. d'Hulst, Christophe Long, Carole A. Ball, Steven G. Tomavo, Stanislas TI Engineering the Chloroplast Targeted Malarial Vaccine Antigens in Chlamydomonas Starch Granules SO PLOS ONE LA English DT Article ID PLASMODIUM-FALCIPARUM MALARIA; APICAL MEMBRANE ANTIGEN-1; BLOOD-STAGE VACCINE; IN-VITRO; REINHARDTII; AMYLOPECTIN; INVASION; AMYLOSE; BIOSYNTHESIS; ANTIBODIES AB Background: Malaria, an Anopheles-borne parasitic disease, remains a major global health problem causing illness and death that disproportionately affects developing countries. Despite the incidence of malaria, which remains one of the most severe infections of human populations, there is no licensed vaccine against this life-threatening disease. In this context, we decided to explore the expression of Plasmodium vaccine antigens fused to the granule bound starch synthase (GBSS), the major protein associated to the starch matrix in all starch-accumulating plants and algae such as Chlamydomonas reinhardtii. Methods and Findings: We describe the development of genetically engineered starch granules containing plasmodial vaccine candidate antigens produced in the unicellular green algae Chlamydomonas reinhardtii. We show that the C-terminal domains of proteins from the rodent Plasmodium species, Plasmodium berghei Apical Major Antigen AMA1, or Major Surface Protein MSP1 fused to the algal granule bound starch synthase (GBSS) are efficiently expressed and bound to the polysaccharide matrix. Mice were either immunized intraperitoneally with the engineered starch particles and Freund adjuvant, or fed with the engineered particles co-delivered with the mucosal adjuvant, and challenged intraperitoneally with a lethal inoculum of P. Berghei. Both experimental strategies led to a significantly reduced parasitemia with an extension of life span including complete cure for intraperitoneal delivery as assessed by negative blood thin smears. In the case of the starch bound P. falciparum GBSS-MSP1 fusion protein, the immune sera or purified immunoglobulin G of mice immunized with the corresponding starch strongly inhibited in vitro the intra-erythrocytic asexual development of the most human deadly plasmodial species. Conclusion: This novel system paves the way for the production of clinically relevant plasmodial antigens as algal starch-based particles designated herein as amylosomes, demonstrating that efficient production of edible vaccines can be genetically produced in Chlamydomonas. C1 [Dauvillee, David; Delhaye, Stephane; Gruyer, Sebastien; d'Hulst, Christophe; Ball, Steven G.; Tomavo, Stanislas] Univ Sci & Technol Lille, CNRS, UGSF, UMR 8576, Villeneuve Dascq, France. [Delhaye, Stephane; Tomavo, Stanislas] Univ Lille Nord France, Inst Pasteur Lille, INSERM, Ctr Infect & Immun Lille,CNRS,UMR 8204,U1019, Lille, France. [Slomianny, Christian] Univ Sci & Technol Lille, INSERM, U1003, Lab Physiol Cellulaire, Villeneuve Dascq, France. [Moretz, Samuel E.; Long, Carole A.] NIAID, Lab Malaria & Vector Res, NIH, Rockville, MD USA. RP Dauvillee, D (reprint author), Univ Sci & Technol Lille, CNRS, UGSF, UMR 8576, Villeneuve Dascq, France. EM Stan.Tomavo@pasteur-lille.fr OI Ball, Steven/0000-0003-1629-1650; Dauvillee, David/0000-0002-0751-9193 FU Centre National de la Recherche Scientifique (CNRS); Institut Medicale de la Recherche Scientifique (INSERM); Institut Pasteur de Lille (IPL) FX This research was funded by the Centre National de la Recherche Scientifique (CNRS), Institut Medicale de la Recherche Scientifique (INSERM) and the Institut Pasteur de Lille (IPL). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 34 TC 24 Z9 25 U1 0 U2 11 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA SN 1932-6203 J9 PLOS ONE JI PLoS One PD DEC 15 PY 2010 VL 5 IS 12 AR e15424 DI 10.1371/journal.pone.0015424 PG 8 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 694ZI UT WOS:000285340000025 PM 21179538 ER PT J AU Jeang, KT AF Jeang, Kuan-Teh TI The rise of Bioscience in the East SO RETROVIROLOGY LA English DT Editorial Material AB The rapid growth of bioscience in China is considered. C1 NIH, Bethesda, MD 20892 USA. RP Jeang, KT (reprint author), NIH, Bldg 10, Bethesda, MD 20892 USA. EM kjeang@niaid.nih.gov RI Jeang, Kuan-Teh/A-2424-2008 FU Intramural NIH HHS NR 9 TC 2 Z9 2 U1 0 U2 2 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1742-4690 J9 RETROVIROLOGY JI Retrovirology PD DEC 15 PY 2010 VL 7 AR 106 DI 10.1186/1742-4690-7-106 PG 2 WC Virology SC Virology GA 700ZV UT WOS:000285785000001 PM 21159179 ER PT J AU Andersen, JF AF Andersen, John F. TI Structure and mechanism in salivary proteins from blood-feeding arthropods SO TOXICON LA English DT Article; Proceedings Paper CT 16th World Congress of the International-Society-on-Toxinology/10th Congress of the Brazilian-Society-Toxicology CY MAR, 2009 CL BRAZIL SP Int Soc Toxinol (IST), Brazilian Soc Toxicol DE Lipocalin; Odorant-binding protein; D7; Nitrophorin; Tick; Mosquito; Diptera; X-ray crystallography ID BUG RHODNIUS-PROLIXUS; NITRIC-OXIDE-BINDING; HISTAMINE-BINDING; BLOODSUCKING BUG; HEME PROTEIN; CRYSTAL-STRUCTURE; LIGAND-BINDING; ANTIHEMOSTATIC PROTEIN; COMPLEMENT INHIBITOR; PLATELET-AGGREGATION AB The saliva of blood-feeding arthropods contains rich mixtures of ligand binding proteins targeted at inhibiting hemostasis and inflammation in the host. Since blood feeding has evolved many times, different taxonomic groups utilize completely different families of proteins to perform similar tasks. Structural studies performed on a number of these proteins have revealed biologically novel and sophisticated mechanisms used to perform their functions. Here, the results of these structural and mechanistic studies are reviewed. Published by Elsevier Ltd. C1 NIAID, Lab Malaria & Vector Res, NIH, Rockville, MD 20852 USA. RP Andersen, JF (reprint author), NIAID, Lab Malaria & Vector Res, NIH, 2E-32B Twinbrook 3 Bldg,12735 Twinbrook Pkwy, Rockville, MD 20852 USA. EM jandersen@niaid.nih.gov FU Intramural NIH HHS [Z01 AI001012-01] NR 52 TC 20 Z9 20 U1 1 U2 15 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0041-0101 J9 TOXICON JI Toxicon PD DEC 15 PY 2010 VL 56 IS 7 SI SI BP 1120 EP 1129 DI 10.1016/j.toxicon.2009.11.002 PG 10 WC Pharmacology & Pharmacy; Toxicology SC Pharmacology & Pharmacy; Toxicology GA 710XM UT WOS:000286550300006 PM 19925819 ER PT J AU Francischetti, IMB AF Francischetti, Ivo M. B. TI Platelet aggregation inhibitors from hematophagous animals SO TOXICON LA English DT Article; Proceedings Paper CT 16th World Congress of the International-Society-on-Toxinology/10th Congress of the Brazilian-Society-Toxicology CY MAR, 2009 CL BRAZIL SP Int Soc Toxinol (IST), Brazilian Soc Toxicol DE Platelet aggregation; Hematophagy; Thrombosis; Vascular biology; Sialogenins ID VON-WILLEBRAND-FACTOR; LEECH ANTIPLATELET PROTEIN; GLYCOPROTEIN-IIB-IIIA; HAEMENTERIA-OFFICINALIS LEECH; TICK ORNITHODOROS-MOUBATA; BLOOD-FEEDING INSECT; FORMATION IN-VIVO; SALIVARY-GLANDS; SOFT TICK; RHODNIUS-PROLIXUS AB Salivary glands from blood-sucking animals (e.g., mosquitoes, bugs, sand flies, fleas, ticks, leeches, hookworms, bats) are a rich source of bioactive molecules that counteract hemostasis in a redundant and synergistic manner. This review discusses recent progress in the identification of salivary inhibitors of platelet aggregation, their molecular characterization, and detailed mechanism of action. Diversity of inhibitors is remarkable, with distinct families of proteins characterized as apyrases that enzymatically degrade ADP or as collagen-binding proteins that prevent its interaction with vWF, or platelet integrin alpha 2 beta 1 or GPVI. Molecules that bind ADP. TXA(2), epinephrine, or serotonin with high affinity have also been cloned, expressed, and their structure determined. In addition, a repertoire of antithrombins and an increasingly number of RGD and non-RGD disintegrins targeting platelet alpha IIb beta 3 have been reported. Moreover, metalloproteases with fibrinogen(olytic) activity and PAF phosphorylcholine hydrolase are enzymes that have been recruited to the salivary gland to block platelet aggregation. Platelet inhibitory prostaglandins, lysophosphatydilcholine, adenosine, and nitric oxide (NO)-carrying proteins are other notable examples of molecules from hematophagous salivary secretions (herein named sialogenins) with antihemostatic properties. Sialogenins have been employed as tools in biochemistry and cell biology and also display potential therapeutic applications. Published by Elsevier Ltd. C1 NIAID, Vector Biol Sect, Lab Malaria & Vector Res, NIH, Bethesda, MD 20892 USA. RP Francischetti, IMB (reprint author), NIAID, Vector Biol Sect, Lab Malaria & Vector Res, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA. EM ifrancischetti@niaid.nih.gov FU Intramural NIH HHS [Z01 AI000810-11, Z99 AI999999] NR 85 TC 54 Z9 55 U1 1 U2 13 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0041-0101 J9 TOXICON JI Toxicon PD DEC 15 PY 2010 VL 56 IS 7 SI SI BP 1130 EP 1144 DI 10.1016/j.toxicon.2009.12.003 PG 15 WC Pharmacology & Pharmacy; Toxicology SC Pharmacology & Pharmacy; Toxicology GA 710XM UT WOS:000286550300007 PM 20035779 ER PT J AU Pasha, O Goldenberg, RL McClure, EM Saleem, S Goudar, SS Althabe, F Patel, A Esamai, F Garces, A Chomba, E Mazariegos, M Kodkany, B Belizan, JM Derman, RJ Hibberd, PL Carlo, WA Liechty, EA Hambidge, KM Buekens, P Wallace, D Howard-Grabman, L Stalls, S Koso-Thomas, M Jobe, AH Wright, LL AF Pasha, Omrana Goldenberg, Robert L. McClure, Elizabeth M. Saleem, Sarah Goudar, Shivaprasad S. Althabe, Fernando Patel, Archana Esamai, Fabian Garces, Ana Chomba, Elwyn Mazariegos, Manolo Kodkany, Bhala Belizan, Jose M. Derman, Richard J. Hibberd, Patricia L. Carlo, Waldemar A. Liechty, Edward A. Hambidge, K. Michael Buekens, Pierre Wallace, Dennis Howard-Grabman, Lisa Stalls, Suzanne Koso-Thomas, Marion Jobe, Alan H. Wright, Linda L. TI Communities, birth attendants and health facilities: a continuum of emergency maternal and newborn care (the global network's EmONC trial) SO BMC PREGNANCY AND CHILDBIRTH LA English DT Article ID RANDOMIZED CONTROLLED-TRIAL; OBSTETRIC CARE; DEVELOPING-COUNTRIES; PERINATAL-MORTALITY; NEONATAL DEATHS; SURVIVAL 1; NEPAL; INTERVENTION; PREPAREDNESS; STILLBIRTH AB Background: Maternal and newborn mortality rates remain unacceptably high, especially where the majority of births occur in home settings or in facilities with inadequate resources. The introduction of emergency obstetric and newborn care services has been proposed by several organizations in order to improve pregnancy outcomes. However, the effectiveness of emergency obstetric and neonatal care services has never been proven. Also unproven is the effectiveness of community mobilization and community birth attendant training to improve pregnancy outcomes. Methods/Design: We have developed a cluster-randomized controlled trial to evaluate the impact of a comprehensive intervention of community mobilization, birth attendant training and improvement of quality of care in health facilities on perinatal mortality in low and middle-income countries where the majority of births take place in homes or first level care facilities. This trial will take place in 106 clusters (300-500 deliveries per year each) across 7 sites of the Global Network for Women's and Children's Health Research in Argentina, Guatemala, India, Kenya, Pakistan and Zambia. The trial intervention has three key elements, community mobilization, home-based life saving skills for communities and birth attendants, and training of providers at obstetric facilities to improve quality of care. The primary outcome of the trial is perinatal mortality. Secondary outcomes include rates of stillbirth, 7-day neonatal mortality, maternal death or severe morbidity (including obstetric fistula, eclampsia and obstetrical sepsis) and 28-day neonatal mortality. Discussion: In this trial, we are evaluating a combination of interventions including community mobilization and facility training in an attempt to improve pregnancy outcomes. If successful, the results of this trial will provide important information for policy makers and clinicians as they attempt to improve delivery services for pregnant women and newborns in low-income countries. C1 [Pasha, Omrana; Saleem, Sarah] Aga Khan Univ, Dept Community Hlth Sci, Karachi, Pakistan. [Goldenberg, Robert L.] Drexel Univ, Dept Obstet & Gynecol, Philadelphia, PA 19104 USA. [McClure, Elizabeth M.; Wallace, Dennis] Res Triangle Inst, Dept Stat & Epidemiol, Durham, NC USA. [Goudar, Shivaprasad S.; Kodkany, Bhala] Jawaharlal Nehru Med Coll, KLE Res Fdn, Belgaum, India. [Althabe, Fernando; Belizan, Jose M.] Univ Buenos Aires, Inst Clin Effectiveness & Hlth Policy, Buenos Aires, DF, Argentina. [Patel, Archana] Indira Gandhi Govt Med Coll, Dept Pediat, Nagpur, Maharashtra, India. [Esamai, Fabian] Moi Univ, Dept Pediat, Eldoret, Kenya. [Garces, Ana] San Carlos Univ, Guatemala City, Guatemala. [Chomba, Elwyn] Univ Zambia, Dept Pediat, Lusaka, Zambia. [Mazariegos, Manolo] ECLAMP, Guatemala City, Guatemala. [Derman, Richard J.] Christiana Hlth Care, Dept Obstet & Gynecol, Delaware, OH USA. [Hibberd, Patricia L.] Partners Hlth Org, Boston, MA USA. [Carlo, Waldemar A.] Univ Alabama Birmingham, Dept Pediat, Birmingham, AL USA. [Liechty, Edward A.] Indiana Univ, Dept Pediat, Indianapolis, IN 46204 USA. [Hambidge, K. Michael] Univ Colorado, Denver, CO 80202 USA. [Buekens, Pierre] Tulane Sch Publ Hlth & Trop Med, New Orleans, LA USA. [Howard-Grabman, Lisa] TRG Inc, Alexandria, VA USA. [Koso-Thomas, Marion; Wright, Linda L.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Bethesda, MD USA. [Jobe, Alan H.] Cincinnati Childrens Hosp, Dept Pediat, Cincinnati, OH USA. RP Pasha, O (reprint author), Aga Khan Univ, Dept Community Hlth Sci, Karachi, Pakistan. EM omrana.pasha@aku.edu OI GOUDAR, SHIVAPRASAD/0000-0002-8680-7053; Belizan, Jose/0000-0002-8412-3010 FU Eunice Kennedy Shriver National Institute on Child Health and Human Development; Eunice Kennedy Shriver National Institute of Child health and Human Development (NICHD), of the National Institutes of Health in the United States FX This project is funded by grants from the Eunice Kennedy Shriver National Institute on Child Health and Human Development.; This project is being funded by the Eunice Kennedy Shriver National Institute of Child health and Human Development (NICHD), of the National Institutes of Health in the United States. The authors of this paper have no competing interests to declare. NR 59 TC 31 Z9 32 U1 4 U2 15 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1471-2393 J9 BMC PREGNANCY CHILDB JI BMC Pregnancy Childbirth PD DEC 14 PY 2010 VL 10 AR 82 DI 10.1186/1471-2393-10-82 PG 9 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 840RB UT WOS:000296457300001 PM 21156060 ER PT J AU Yaseen, Z Katz, C Johnson, MS Eisenberg, D Cohen, LJ Galynker, II AF Yaseen, Zimri Katz, Curren Johnson, Matthew S. Eisenberg, Daniel Cohen, Lisa J. Galynker, Igor I. TI Construct development: The Suicide Trigger Scale (STS-2), a measure of a hypothesized suicide trigger state SO BMC PSYCHIATRY LA English DT Article ID SEQUENCED TREATMENT ALTERNATIVES; RISK-FACTORS; PSYCHOLOGICAL DISTRESS; ASTERISK-D; IDEATION; BEHAVIOR; DEPRESSION; ADOLESCENTS; COMORBIDITY; PREVENTION AB Background: This study aims to develop the construct of a 'suicide trigger state' by exploring data gathered with a novel psychometric self-report instrument, the STS-2. Methods: The STS-2, was administered to 141 adult psychiatric patients with suicidal ideation. Multiple statistical methods were used to explore construct validity and structure. Results: Cronbach's alpha (0.949) demonstrated excellent internal consistency. Factor analyses yielded two-component solutions with good agreement. The first component described near-psychotic somatization and ruminative flooding, while the second described frantic hopelessness. ROC analysis determined an optimal cut score for a history of suicide attempt, with significance of p < 0.03. Logistic regression analysis found items sensitive to history of suicide attempt described ruminative flooding, doom, hopelessness, entrapment and dread. Conclusions: The STS-2 appears to measure a distinct and novel clinical entity, which we speculatively term the 'suicide trigger state.' High scores on the STS-2 associate with reported history of past suicide attempt. C1 [Yaseen, Zimri; Katz, Curren; Cohen, Lisa J.; Galynker, Igor I.] Beth Israel Deaconess Med Ctr, New York, NY 10003 USA. [Johnson, Matthew S.] Columbia Univ, Teachers Coll, New York, NY 10027 USA. [Eisenberg, Daniel] NIMH, Bethesda, MD 20892 USA. RP Yaseen, Z (reprint author), Beth Israel Deaconess Med Ctr, New York, NY 10003 USA. EM zsyaseen@gmail.com RI Eisenberg, Daniel/C-7432-2014; Katz, Curren/J-4197-2014; Eisenberg, Daniel/S-4342-2016; OI Katz, Curren/0000-0002-0125-9861; Yaseen, Zimri/0000-0003-4103-2511; Johnson, Matthew/0000-0003-3157-4165 FU Hope for Depression Research Foundation; Empire Clinical Research Investigator Program; Family Center for Bipolar Disorder; Zirinsky Mood Disorders Center FX This research was supported in part by the Hope for Depression Research Foundation, the Empire Clinical Research Investigator Program, the Family Center for Bipolar Disorder, and the Zirinsky Mood Disorders Center. This research was presented in part at the following meetings: Yaseen Z, Johnson M, Galynker I. Construct Validity of a Suicide Trigger State. The 162nd Annual Meeting of the American Psychiatric Association, San Francisco, CA (2009) NR 48 TC 11 Z9 11 U1 3 U2 6 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1471-244X J9 BMC PSYCHIATRY JI BMC Psychiatry PD DEC 14 PY 2010 VL 10 AR 110 DI 10.1186/1471-244X-10-110 PG 11 WC Psychiatry SC Psychiatry GA 702WM UT WOS:000285926600001 PM 21144063 ER PT J AU den Elzen, WPJ Willems, JM Westendorp, RGJ de Craen, AJM Blauw, GJ Ferrucci, L Assendelft, WJJ Gussekloo, J AF den Elzen, Wendy P. J. Willems, Jorien M. Westendorp, Rudi G. J. de Craen, Anton J. M. Blauw, Gerard Jan Ferrucci, Luigi Assendelft, Willem J. J. Gussekloo, Jacobijn TI Effect of erythropoietin levels on mortality in old age: the Leiden 85-plus Study SO CANADIAN MEDICAL ASSOCIATION JOURNAL LA English DT Article ID RECOMBINANT-HUMAN-ERYTHROPOIETIN; CONGESTIVE-HEART-FAILURE; ENDOGENOUS ERYTHROPOIETIN; SERUM ERYTHROPOIETIN; PROGNOSTIC VALUE; EPOETIN-ALPHA; METAANALYSIS; CANCER; PREDICTION; QUALITY AB Background: The production of erythropoietin is triggered by impaired oxygen delivery to the kidney, either because of anemia or hypoxemia. High erythropoietin levels have been shown to predict the risk of death among patients with chronic heart failure. We investigated the prognostic value of elevated erythropoietin levels on mortality among very elderly people in the general population. Methods: The Leiden 85-plus Study is a population-based prospective follow-up study involving 599 people aged 85 years in Leiden, the Netherlands, enrolled between September 1997 and September 1999. Erythropoietin levels were determined at age 86. For this analysis, we included 428 participants with a creatinine clearance of at least 30 mL/min. Mortality data, recorded until Feb. 1, 2008, were obtained from the municipal registry. Results: During follow-up, 324 (75.7%) participants died. Compared with participants whose erythropoietin levels were in the lowest tertile (reference group), those whose levels were in the middle tertile had a 25% increased risk of death (hazard ratio [HR] 1.25, 95% confidence interval [CI] 0.95-1.64), and those whose levels were in the highest tertile had a 73% increased risk (HR 1.73, 95% CI 1.32-2.26) (p value for trend < 0.01). The association between erythropoietin levels and mortality remained largely unchanged after we adjusted for sex, creatinine clearance, hemoglobin level, comorbidity, smoking status and C-reactive protein level, and was similar for deaths from cardiovascular and noncardiovascular causes. Interpretation: Among people aged 85 years and older, elevated erythropoietin levels were associated with an in creased risk of death, independent of hemoglobin levels. C1 [den Elzen, Wendy P. J.; Assendelft, Willem J. J.; Gussekloo, Jacobijn] Leiden Univ, Med Ctr, Dept Publ Hlth & Primary Care, NL-2300 RC Leiden, Netherlands. [Willems, Jorien M.; Westendorp, Rudi G. J.; de Craen, Anton J. M.; Blauw, Gerard Jan] Leiden Univ, Med Ctr, Dept Gerontol & Geriatr, NL-2300 RC Leiden, Netherlands. [Westendorp, Rudi G. J.] Netherlands Consortium Healthy Ageing, Leiden, Netherlands. [Blauw, Gerard Jan] Bronovo Hosp, Dept Internal Med, The Hague, Netherlands. [Ferrucci, Luigi] NIA, Longitudinal Studies Sect, Clin Res Branch, NIH, Baltimore, MD 21224 USA. RP den Elzen, WPJ (reprint author), Leiden Univ, Med Ctr, Dept Publ Hlth & Primary Care, POB 9600, NL-2300 RC Leiden, Netherlands. EM w.p.j.den_elzen@lumc.nl RI Assendelft, W.J.J./H-8008-2014 FU Dutch Ministry of Health, Welfare and Sports; US National Institute on Aging, National Institute of Health FX The Leiden 85-plus Study was funded in part by an unrestricted grant from the Dutch Ministry of Health, Welfare and Sports. This study was supported by the Intramural Research Program of the US National Institute on Aging, National Institute of Health. The sponsor had no role in the design and conduct of the study; in the collection, analysis and interpretation of the data; or in the preparation, review and approval of the manuscript. NR 32 TC 11 Z9 11 U1 0 U2 0 PU CMA-CANADIAN MEDICAL ASSOC PI OTTAWA PA 1867 ALTA VISTA DR, OTTAWA, ONTARIO K1G 5W8, CANADA SN 0820-3946 EI 1488-2329 J9 CAN MED ASSOC J JI Can. Med. Assoc. J. PD DEC 14 PY 2010 VL 182 IS 18 BP 1953 EP 1958 DI 10.1503/cmaj.100374 PG 6 WC Medicine, General & Internal SC General & Internal Medicine GA 690JD UT WOS:000284998700034 PM 21149533 ER PT J AU Edwards, LA Fine, HA AF Edwards, Lincoln A. Fine, Howard A. TI The Ids Have It SO CANCER CELL LA English DT Editorial Material ID TGF-BETA; LUNG METASTASIS; STEM-CELLS; CANCER; TUMORS AB In this issue of Cancer Cell, Anido et al. demonstrate that Id1 is the likely arbiter of divergent transforming growth factor-beta (TGF-beta) signaling in glioma-initiating cells (GICs) from different tumors. These findings hold both the promise and potential peril of therapeutic targeting of the TGF-beta pathway. C1 [Edwards, Lincoln A.; Fine, Howard A.] NINDS, Neurooncol Branch, NCI, NIH, Bethesda, MD 20892 USA. RP Fine, HA (reprint author), NINDS, Neurooncol Branch, NCI, NIH, Bethesda, MD 20892 USA. EM hfine@mail.nih.gov NR 10 TC 1 Z9 4 U1 0 U2 0 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 1535-6108 J9 CANCER CELL JI Cancer Cell PD DEC 14 PY 2010 VL 18 IS 6 BP 543 EP 545 DI 10.1016/j.ccr.2010.11.028 PG 3 WC Oncology; Cell Biology SC Oncology; Cell Biology GA 697PL UT WOS:000285527300004 PM 21156278 ER PT J AU Rui, LX Emre, NCT Kruhlak, MJ Chung, HJ Steidl, C Slack, G Wright, GW Lenz, G Ngo, VN Shaffer, AL Xu, WH Zhao, H Yang, YD Lamy, L Davis, RE Xiao, WM Powell, J Maloney, D Thomas, CJ Moller, P Rosenwald, A Ott, G Muller-Hermelink, HK Savage, K Connors, JM Rimsza, LM Campo, E Jaffe, ES Delabie, J Smeland, EB Weisenburger, DD Chan, WC Gascoyne, RD Levens, D Staudt, LM AF Rui, Lixin Emre, N. C. Tolga Kruhlak, Michael J. Chung, Hye-Jung Steidl, Christian Slack, Graham Wright, George W. Lenz, Georg Ngo, Vu N. Shaffer, Arthur L. Xu, Weihong Zhao, Hong Yang, Yandan Lamy, Laurence Davis, R. Eric Xiao, Wenming Powell, John Maloney, David Thomas, Craig J. Moeller, Peter Rosenwald, Andreas Ott, German Muller-Hermelink, Hans Konrad Savage, Kerry Connors, Joseph M. Rimsza, Lisa M. Campo, Elias Jaffe, Elaine S. Delabie, Jan Smeland, Erlend B. Weisenburger, Dennis D. Chan, Wing C. Gascoyne, Randy D. Levens, David Staudt, Louis M. TI Cooperative Epigenetic Modulation by Cancer Amplicon Genes SO CANCER CELL LA English DT Article ID B-CELL LYMPHOMA; CLASSICAL HODGKIN LYMPHOMA; REED-STERNBERG CELLS; EXON 12 MUTATIONS; HISTONE H3; JAK2 INHIBITOR; INTERLEUKIN-13 RECEPTOR; MOLECULAR SIGNATURE; POLYCYTHEMIA-VERA; LYSINE 9 AB Chromosome band 9p24 is frequently amplified in primary mediastinal B cell lymphoma (PMBL) and Hodgkin lymphoma (HL). To identify oncogenes in this amplicon, we screened an RNA interference library targeting amplicon genes and thereby identified JAK2 and the histone demethylase JMJD2C as essential genes in these lymphomas. Inhibition of JAK2 and JMJD2C cooperated in killing these lymphomas by decreasing tyrosine 41 phosphorylation and increasing lysine 9 trimethylation of histone H3, promoting heterochromatin formation. MYC, a major target of JAK2-mediated histone phosphorylation, was silenced after JAK2 and JMJD2C inhibition, with a corresponding increase in repressive chromatin. Hence, JAK2 and JMJD2C cooperatively remodel the PMBL and HL epigenome, offering a mechanistic rationale for the development of JAK2 and JMJD2C inhibitors in these diseases. C1 [Rui, Lixin; Emre, N. C. Tolga; Lenz, Georg; Ngo, Vu N.; Shaffer, Arthur L.; Xu, Weihong; Zhao, Hong; Yang, Yandan; Lamy, Laurence; Davis, R. Eric; Staudt, Louis M.] NCI, Metab Branch, Bethesda, MD 20892 USA. [Kruhlak, Michael J.] NCI, Expt Immunol Branch, Bethesda, MD 20892 USA. [Chung, Hye-Jung; Jaffe, Elaine S.; Levens, David] NCI, Pathol Lab, Ctr Canc Res, Bethesda, MD 20892 USA. [Steidl, Christian; Slack, Graham; Savage, Kerry; Connors, Joseph M.; Gascoyne, Randy D.] British Columbia Canc Agcy, Vancouver, BC V5Z 4E6, Canada. [Wright, George W.] NCI, Biometr Res Branch, DCTD, NIH, Bethesda, MD 20892 USA. [Xiao, Wenming; Powell, John] NIH, Bioinformat & Mol Anal Sect, Div Computat Biosci, Ctr Informat Technol, Bethesda, MD 20892 USA. [Maloney, David; Thomas, Craig J.] NHGRI, NIH Chem Genom Ctr, NIH, Rockville, MD 20850 USA. [Moeller, Peter] Univ Ulm, Dept Pathol, D-89081 Ulm, Germany. [Rosenwald, Andreas; Muller-Hermelink, Hans Konrad] Univ Wurzburg, Dept Pathol, D-97080 Wurzburg, Germany. [Ott, German] Robert Bosch Krankenhaus, Dept Clin Pathol, D-70376 Stuttgart, Germany. [Ott, German] Dr Margarete Fischer Bosch Inst Clin Pharmacol, D-70376 Stuttgart, Germany. [Rimsza, Lisa M.] Univ Arizona, Dept Pathol, Tucson, AZ 85724 USA. [Rimsza, Lisa M.] SW Oncol Grp, Ann Arbor, MI 48106 USA. [Campo, Elias] Univ Barcelona, Hosp Clin, E-08036 Barcelona, Spain. [Delabie, Jan] Oslo Univ Hosp, Pathol Clin, N-0027 Oslo, Norway. [Smeland, Erlend B.] Oslo Univ Hosp, Inst Canc Res, N-0027 Oslo, Norway. [Smeland, Erlend B.] Univ Oslo, Ctr Canc Biomed, N-0316 Oslo, Norway. [Weisenburger, Dennis D.; Chan, Wing C.] Univ Nebraska, Dept Pathol, Omaha, NE 68198 USA. [Weisenburger, Dennis D.; Chan, Wing C.] Univ Nebraska, Dept Microbiol, Omaha, NE 68198 USA. RP Staudt, LM (reprint author), NCI, Metab Branch, Bethesda, MD 20892 USA. EM lstaudt@mail.nih.gov RI Lenz, Georg/I-6844-2012; Levens, David/C-9216-2009; OI Levens, David/0000-0002-7616-922X; Campo, elias/0000-0001-9850-9793; Delabie, Jan/0000-0001-5023-0689; Jaffe, Elaine/0000-0003-4632-0301 FU NIH, National Cancer Institute, Center for Cancer Research; NCI [UO1-CA 114778]; National Health and Medical Research Council (NHMRC) of Australia; German Research Foundation (DFG); Cancer Research Society of Canada; Terry Fox Foundation [019001]; Canadian Institutes for Health [178536] FX This research was supported by the Intramural Research Program of the NIH, National Cancer Institute, Center for Cancer Research and an NCI SPECS grant (UO1-CA 114778). L.R. is the recipient of a C.J. Martin Fellowship from the National Health and Medical Research Council (NHMRC) of Australia. G.L. was also supported by a research grant from the German Research Foundation (DFG). C.S. is funded by a fellowship award from the Cancer Research Society of Canada. R.D.G. is funded by a Terry Fox Foundation award (019001) and a Canadian Institutes for Health Research grant (178536). We thank Dennis Huszar of AstraZeneca for providing AZD1480. NR 54 TC 137 Z9 137 U1 2 U2 13 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 1535-6108 J9 CANCER CELL JI Cancer Cell PD DEC 14 PY 2010 VL 18 IS 6 BP 590 EP 605 DI 10.1016/j.ccr.2010.11.013 PG 16 WC Oncology; Cell Biology SC Oncology; Cell Biology GA 697PL UT WOS:000285527300010 PM 21156283 ER PT J AU Olin, JW Allie, DE Belkin, M Bonow, RO Casey, DE Creager, MA Gerber, TC Hirsch, AT Jaff, MR Kaufman, JA Lewis, CA Martin, ET Martin, LG Sheehan, P Stewart, KJ Treat-Jacobson, D White, CJ Zheng, ZJ Masoudi, FA DeLong, E Erwin, JP Goff, DC Grady, K Green, LA Heidenreich, PA Jenkins, KJ Loth, AR Peterson, ED Shahian, DM Brindis, RG Lewin, JC May, C Shahriary, M Chiu, JS Barrett, EA Brown, N Robertson, RM Whitman, GR Randle, D AF Olin, Jeffrey W. Allie, David E. Belkin, Michael Bonow, Robert O. Casey, Donald E., Jr. Creager, Mark A. Gerber, Thomas C. Hirsch, Alan T. Jaff, Michael R. Kaufman, John A. Lewis, Curtis A. Martin, Edward T. Martin, Louis G. Sheehan, Peter Stewart, Kerry J. Treat-Jacobson, Diane White, Christopher J. Zheng, Zhi-Jie Masoudi, Frederick A. DeLong, Elizabeth Erwin, John P., III Goff, David C., Jr. Grady, Kathleen Green, Lee A. Heidenreich, Paul A. Jenkins, Kathy J. Loth, Ann R. Peterson, Eric D. Shahian, David M. Brindis, Ralph G. Lewin, John C. May, Charlene Shahriary, Melanie Chiu, Jensen S. Barrett, Erin A. Brown, Nancy Robertson, Rose Marie Whitman, Gayle R. Randle, Dwight CA Amer Coll Cardiology Fdn Amer Heart Assoc Task Force Perfor TI ACCF/AHA/ACR/SCAI/SIR/SVM/SVN/SVS 2010 Performance Measures for Adults With Peripheral Artery Disease A Report of the American College of Cardiology Foundation/American Heart Association Task Force on Performance Measures, the American College of Radiology, the Society for Cardiac Angiography and Interventions, the Society for Interventional Radiology, the Society for Vascular Medicine, the Society for Vascular Nursing, and the Society for Vascular Surgery (Writing Committee to Develop Clinical Performance Measures for Peripheral Artery Disease) SO CIRCULATION LA English DT Article DE AHA Scientific Statements; abdominal aortic aneurysm; ankle brachial index; peripheral arterial disease; secondary prevention; supervised exercise ID ABDOMINAL AORTIC-ANEURYSM; ANKLE-BRACHIAL INDEX; REHABILITATION/SECONDARY PREVENTION SERVICES; ELEVATION MYOCARDIAL-INFARCTION; CARDIOVASCULAR-DISEASE; INTERMITTENT CLAUDICATION; GENERAL-POPULATION; CONTROLLED-TRIAL; ST-ELEVATION; FOLLOW-UP C1 [Zheng, Zhi-Jie] NHLBI, Bethesda, MD USA. RI White, Christopher/J-6686-2012 OI White, Christopher/0000-0001-8618-7539 NR 73 TC 35 Z9 36 U1 1 U2 8 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD DEC 14 PY 2010 VL 122 IS 24 BP 2583 EP 2618 DI 10.1161/CIR.0b013e3182031a3c PG 36 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 693RN UT WOS:000285243200018 PM 21126978 ER PT J AU Liu, LH Das, S Losert, W Parent, CA AF Liu, Lunhua Das, Satarupa Losert, Wolfgang Parent, Carole A. TI mTORC2 Regulates Neutrophil Chemotaxis in a cAMP- and RhoA-Dependent Fashion SO DEVELOPMENTAL CELL LA English DT Article ID PROTEIN-KINASE-A; ADENYLYL-CYCLASE; CYCLIC-AMP; MEDIATED ACTIVATION; CELL-MIGRATION; SIGNAL RELAY; CHEMOATTRACTANT RECEPTOR; PHOSPHORYLATION; DICTYOSTELIUM; PATHWAY AB We studied the role of the target of rapamycin complex 2 (mTORC2) during neutrophil chemotaxis, a process that is mediated through the polarization of actin and myosin filament networks. We show that inhibition of mTORC2 activity, achieved via knock down (KD) of Rictor, severely inhibits neutrophil polarization and directed migration induced by chemoattractants, independently of Akt. Rictor KD also abolishes the ability of chemoattractants to induce cAMP production, a process mediated through the activation of the adenylyl cyclase 9 (AC9). Cells with either reduced or higher AC9 levels also exhibit specific and severe tail retraction defects that are mediated through RhoA. We further show that cAMP is excluded from extending pseudopods and remains restricted to the cell body of migrating neutrophils. We propose that the mTORC2-dependent regulation of Myoll occurs through a cAMP/RhoA-signaling axis, independently of actin reorganization during neutrophil chemotaxis. C1 [Liu, Lunhua; Das, Satarupa; Losert, Wolfgang; Parent, Carole A.] NCI, Cellular & Mol Biol Lab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. [Losert, Wolfgang] Univ Maryland, Dept Phys, College Pk, MD 20742 USA. RP Parent, CA (reprint author), NCI, Cellular & Mol Biol Lab, Ctr Canc Res, NIH, Bldg 37, Bethesda, MD 20892 USA. EM parentc@mail.nih.gov OI Das, Satarupa/0000-0002-4217-9972 FU Center for Cancer Research, NCI, National Institutes of Health FX We thank Drs. Daniel Storm for providing the cDNA encoding AC3 and AC9, Henry Bourne for providing the PLB-985 cells, and Paul Randazzo for providing the Rhotekin-sepharose beads and for helpful advice. We also wish to thank the C.A.P. laboratory members for excellent discussions and suggestions and for valuable input on the manuscript. A special thanks goes to Dr. Valerie Barr for her help with the microscopy. W.L. performed this work while on sabbatical at the LCMB, CCR. This research was supported by the Intramural Research Program of the Center for Cancer Research, NCI, National Institutes of Health. NR 66 TC 88 Z9 92 U1 1 U2 4 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 1534-5807 J9 DEV CELL JI Dev. Cell PD DEC 14 PY 2010 VL 19 IS 6 BP 845 EP 857 DI 10.1016/j.devcel.2010.11.004 PG 13 WC Cell Biology; Developmental Biology SC Cell Biology; Developmental Biology GA 696OH UT WOS:000285450200010 PM 21145500 ER EF