FN Thomson Reuters Web of Science™ VR 1.0 PT J AU Li, CY Liu, QR Zhang, PW Li, XM Wei, LP Uhl, GR AF Li, Chuan-Yun Liu, Qing-Rong Zhang, Ping-Wu Li, Xiao-Mo Wei, Liping Uhl, George R. TI OKCAM: an ontology-based, human-centered knowledgebase for cell adhesion molecules SO NUCLEIC ACIDS RESEARCH LA English DT Article ID PATHWAY IDENTIFICATION; INTERACTION NETWORK; ALCOHOL DEPENDENCE; HUMAN GENOME; COPY-NUMBER; 2008 UPDATE; DATABASE; PROTEIN; ASSOCIATION; EXPRESSION AB 'Cell adhesion molecules' (CAMs) are essential elements of cell/cell communication that are important for proper development and plasticity of a variety of organs and tissues. In the brain, appropriate assembly and tuning of neuronal connections is likely to require appropriate function of many cell adhesion processes. Genetic studies have linked and/or associated CAM variants with psychiatric, neurologic, neoplastic, immunologic and developmental phenotypes. However, despite increasing recognition of their functional and pathological significance, no systematic study has enumerated CAMs or documented their global features. We now report compilation of 496 human CAM genes in six gene families based on manual curation of protein domain structures, Gene Ontology annotations, and 1487 NCBI Entrez annotations. We map these genes onto a cell adhesion molecule ontology that contains 850 terms, up to seven levels of depth and provides a hierarchical description of these molecules and their functions. We develop OKCAM, a CAM knowledgebase that provides ready access to these data and ontologic system at http://okcam.cbi.pku.edu.cn. We identify global CAM properties that include: (i) functional enrichment, (ii) over-represented regulation modes and expression patterns and (iii) relationships to human Mendelian and complex diseases, and discuss the strengths and limitations of these data. C1 [Li, Chuan-Yun; Liu, Qing-Rong; Zhang, Ping-Wu; Uhl, George R.] NIDA, Mol Neurobiol Branch, NIH, IRP, Baltimore, MD 21224 USA. [Li, Chuan-Yun; Li, Xiao-Mo; Wei, Liping] Peking Univ, Coll Life Sci, Ctr Bioinformat, Natl Lab Prot Engn & Plant Genet Engn, Beijing 100871, Peoples R China. RP Uhl, GR (reprint author), NIDA, Mol Neurobiol Branch, NIH, IRP, Baltimore, MD 21224 USA. EM guhl@intra.nida.nih.gov RI Liu, Qing-Rong/A-3059-2012 OI Liu, Qing-Rong/0000-0001-8477-6452 FU National Institutes of Health Intramural Research Program (NIDA); NIH [P50CA/DA84718]; China Scholarship Council (C.Y.L.); China National High-tech 863 Programs [2006AA02A312, 2006AA02Z334]; 973 Programs [2007CB946904]; NIDA/IRP [P50CA/DA84718] FX National Institutes of Health Intramural Research Program (NIDA), NIH grants P50CA/DA84718; China Scholarship Council (C.Y.L.); China National High-tech 863 Programs (2006AA02A312, 2006AA02Z334); 973 Programs (2007CB946904). Funding for open access charge: NIDA/IRP grants P50CA/DA84718. NR 48 TC 7 Z9 7 U1 0 U2 0 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 2009 VL 37 BP D251 EP D260 DI 10.1093/nar/gkn568 PG 10 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 386TT UT WOS:000261906200046 PM 18790807 ER PT J AU Marchler-Bauer, A Anderson, JB Chitsaz, F Derbyshire, MK DeWeese-Scott, C Fong, JH Geer, LY Geer, RC Gonzales, NR Gwadz, M He, S Hurwitz, DI Jackson, JD Ke, Z Lanczycki, CJ Liebert, CA Liu, C Lu, F Lu, S Marchler, GH Mullokandov, M Song, JS Tasneem, A Thanki, N Yamashita, RA Zhang, D Zhang, N Bryant, SH AF Marchler-Bauer, Aron 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 He, Siqian Hurwitz, David I. Jackson, John D. Ke, Zhaoxi Lanczycki, Christopher J. Liebert, Cynthia A. Liu, Chunlei Lu, Fu Lu, Shennan Marchler, Gabriele H. Mullokandov, Mikhail Song, James S. Tasneem, Asba Thanki, Narmada Yamashita, Roxanne A. Zhang, Dachuan Zhang, Naigong Bryant, Stephen H. TI CDD: specific functional annotation with the Conserved Domain Database SO NUCLEIC ACIDS RESEARCH LA English DT Article ID ALIGNMENTS AB NCBI's Conserved Domain Database (CDD) is a collection of multiple sequence alignments and derived database search models, which represent protein domains conserved in molecular evolution. The collection can be accessed at http://www.ncbi.nlm.nih.gov/Structure/cdd/cdd.shtml, and is also part of NCBI's Entrez query and retrieval system, crosslinked to numerous other resources. CDD provides annotation of domain footprints and conserved functional sites on protein sequences. Precalculated domain annotation can be retrieved for protein sequences tracked in NCBI's Entrez system, and CDD's collection of models can be queried with novel protein sequences via the CD-Search service at http://www.ncbi.nlm.nih.gov/Structure/cdd/wrpsb.cgi. Starting with the latest version of CDD, v2.14, information from redundant and homologous domain models is summarized at a superfamily level, and domain annotation on proteins is flagged as either 'specific' ( identifying molecular function with high confidence) or as 'non-specific' (identifying superfamily membership only). C1 [Marchler-Bauer, Aron; 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; He, Siqian; Hurwitz, David I.; Jackson, John D.; Ke, Zhaoxi; Lanczycki, Christopher J.; Liebert, Cynthia A.; Liu, Chunlei; Lu, Fu; Lu, Shennan; Marchler, Gabriele H.; Mullokandov, Mikhail; Song, James S.; Tasneem, Asba; Thanki, Narmada; Yamashita, Roxanne A.; Zhang, Dachuan; Zhang, Naigong; Bryant, Stephen H.] Natl Lib Med, Natl Ctr Biotechnol Informat, NIH, Bethesda, MD 20894 USA. RP Marchler-Bauer, A (reprint author), Natl Lib Med, Natl Ctr Biotechnol Informat, NIH, Bldg 38 A,Room 8N805,8600 Rockville Pike, Bethesda, MD 20894 USA. EM bauer@ncbi.nlm.nih.gov RI Marchler-Bauer, Aron/A-9681-2009; Sincan, Murat /A-3794-2010; Geer, Lewis/H-2714-2014; OI Marchler-Bauer, Aron/0000-0003-1516-0712 FU Intramural Research Program of the National Library of Medicine at the National Institutes of Health/DHHS FX Intramural Research Program of the National Library of Medicine at National Institutes of Health/DHHS. Funding for open access charge: Intramural Research Program of the National Library of Medicine at the National Institutes of Health/DHHS. NR 13 TC 664 Z9 684 U1 2 U2 38 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 2009 VL 37 BP D205 EP D210 DI 10.1093/nar/gkn845 PG 6 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 386TT UT WOS:000261906200038 PM 18984618 ER PT J AU Novichkov, PS Ratnere, I Wolf, YI Koonin, EV Dubchak, I AF Novichkov, Pavel S. Ratnere, Igor Wolf, Yuri I. Koonin, Eugene V. Dubchak, Inna TI ATGC: a database of orthologous genes from closely related prokaryotic genomes and a research platform for microevolution of prokaryotes SO NUCLEIC ACIDS RESEARCH LA English DT Article ID EVOLUTIONARY GENOMICS; HIGH-THROUGHPUT; ALIGNMENT; BACTERIA; ARCHAEA; TOOL AB The database of Alignable Tight Genomic Clusters (ATGCs) consists of closely related genomes of archaea and bacteria, and is a resource for research into prokaryotic microevolution. Construction of a data set with appropriate characteristics is a major hurdle for this type of studies. With the current rate of genome sequencing, it is difficult to follow the progress of the field and to determine which of the available genome sets meet the requirements of a given research project, in particular, with respect to the minimum and maximum levels of similarity between the included genomes. Additionally, extraction of specific content, such as genomic alignments or families of orthologs, from a selected set of genomes is a complicated and time-consuming process. The database addresses these problems by providing an intuitive and efficient web interface to browse precomputed ATGCs, select appropriate ones and access ATGC-derived data such as multiple alignments of orthologous proteins, matrices of pairwise intergenomic distances based on genome-wide analysis of synonymous and nonsynonymous substitution rates and others. The ATGC database will be regularly updated following new releases of the NCBI RefSeq. The database is hosted by the Genomics Division at Lawrence Berkeley National laboratory and is publicly available at http://atgc.lbl.gov C1 [Novichkov, Pavel S.; Dubchak, Inna] Univ Calif Berkeley, Lawrence Berkeley Lab, Berkeley, CA 94720 USA. [Ratnere, Igor; Dubchak, Inna] Joint Genome Inst, Dept Energy, Walnut Creek, CA 94598 USA. [Wolf, Yuri I.; Koonin, Eugene V.] Natl Ctr Biotechnol Informat, Natl Lib Med, NIH, Bethesda, MD 20894 USA. RP Novichkov, PS (reprint author), Univ Calif Berkeley, Lawrence Berkeley Lab, 1 Cyclotron Rd, Berkeley, CA 94720 USA. EM psnovichkov@lbl.gov FU US Department of Energy [DE-AC02-05CH11231]; Department of Energy Joint Genome Institute; US Department of Health and Human Services FX US Department of Energy (DE-AC02-05CH11231); Department of Energy Joint Genome Institute (to I. R.); the intramural research program of the US Department of Health and Human Services (National Library of Medicine, NIH to Y.I.W. and E.V.K.). NR 26 TC 30 Z9 30 U1 1 U2 6 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 2009 VL 37 BP D448 EP D454 DI 10.1093/nar/gkn684 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 386TT UT WOS:000261906200081 PM 18845571 ER PT J AU Papadopoulos, GL Reczko, M Simossis, VA Sethupathy, P Hatzigeorgiou, AG AF Papadopoulos, Giorgos L. Reczko, Martin Simossis, Victor A. Sethupathy, Praveen Hatzigeorgiou, Artemis G. TI The database of experimentally supported targets: a functional update of TarBase SO NUCLEIC ACIDS RESEARCH LA English DT Article ID CAENORHABDITIS-ELEGANS; MICRORNA TARGETS; RNAS; IDENTIFICATION; RESOURCE AB TarBase5.0 is a database which houses a manually curated collection of experimentally supported microRNA (miRNA) targets in several animal species of central scientific interest, plants and viruses. MiRNAs are small non-coding RNA molecules that exhibit an inhibitory effect on gene expression, interfering with the stability and translational efficiency of the targeted mature messenger RNAs. Even though several computational programs exist to predict miRNA targets, there is a need for a comprehensive collection and description of miRNA targets with experimental support. Here we introduce a substantially extended version of this resource. The current version includes more than 1300 experimentally supported targets. Each target site is described by the miRNA that binds it, the gene in which it occurs, the nature of the experiments that were conducted to test it, the sufficiency of the site to induce translational repression and/or cleavage, and the paper from which all these data were extracted. Additionally, the database is functionally linked to several other relevant and useful databases such as Ensembl, Hugo, UCSC and SwissProt. The TarBase5.0 database can be queried or downloaded from http://microrna.gr/tarbase. C1 [Papadopoulos, Giorgos L.; Reczko, Martin; Simossis, Victor A.; Hatzigeorgiou, Artemis G.] Biomed Sci Res Ctr Alexander Fleming, Inst Mol Oncol, Varkiza 16672, Greece. [Reczko, Martin] Synaptic Ltd, Iraklion 71110, Greece. [Sethupathy, Praveen] NHGRI, Bethesda, MD 20892 USA. [Hatzigeorgiou, Artemis G.] Univ Penn, Philadelphia, PA 19104 USA. RP Papadopoulos, GL (reprint author), Biomed Sci Res Ctr Alexander Fleming, Inst Mol Oncol, Varkiza 16672, Greece. EM gipapado@fleming.gr; hatzigeorgiou@fleming.gr OI Reczko, Martin/0000-0002-0005-8718 FU Aristeia Award from General Secretary Research and Technology, Greece FX Funding for open access charge: Aristeia Award from General Secretary Research and Technology, Greece. NR 19 TC 236 Z9 243 U1 0 U2 4 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 2009 VL 37 BP D155 EP D158 DI 10.1093/nar/gkn809 PG 4 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 386TT UT WOS:000261906200028 PM 18957447 ER PT J AU Pruitt, KD Tatusova, T Klimke, W Maglott, DR AF Pruitt, Kim D. Tatusova, Tatiana Klimke, William Maglott, Donna R. TI NCBI Reference Sequences: current status, policy and new initiatives SO NUCLEIC ACIDS RESEARCH LA English DT Article ID ALIGNMENT; DATABASE; ENTREZ AB NCBI's Reference Sequence (RefSeq) database (http://www.ncbi.nlm.nih.gov/RefSeq/) is a curated non-redundant collection of sequences representing genomes, transcripts and proteins. RefSeq records integrate information from multiple sources and represent a current description of the sequence, the gene and sequence features. The database includes over 5300 organisms spanning prokaryotes, eukaryotes and viruses, with records for more than 5.5 x 10(6) proteins (RefSeq release 30). Feature annotation is applied by a combination of curation, collaboration, propagation from other sources and computation. We report here on the recent growth of the database, recent changes to feature annotations and record types for eukaryotic (primarily vertebrate) species and policies regarding species inclusion and genome annotation. In addition, we introduce RefSeqGene, a new initiative to support reporting variation data on a stable genomic coordinate system. C1 [Pruitt, Kim D.; Tatusova, Tatiana; Klimke, William; Maglott, Donna R.] NIH, Natl Ctr Biotechnol Informat, Natl Lib Med, Bethesda, MD 20892 USA. RP Pruitt, KD (reprint author), NIH, Natl Ctr Biotechnol Informat, Natl Lib Med, Rm 4As 47B,45 Ctr Dr, Bethesda, MD 20892 USA. EM pruitt@ncbi.nlm.nih.gov RI Sincan, Murat /A-3794-2010 FU Intramural Research Program of the National Institute of Health; National Library of Medicine FX Intramural Research Program of the National Institute of Health; National Library of Medicine. Funding for open access charge: Intramural Research Program of the NIH, National Library of Medicine. NR 13 TC 435 Z9 441 U1 1 U2 20 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 2009 VL 37 BP D32 EP D36 DI 10.1093/nar/gkn721 PG 5 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 386TT UT WOS:000261906200006 PM 18927115 ER PT J AU Sayers, EW Barrett, T Benson, DA Bryant, SH Canese, K Chetvernin, V Church, DM DiCuccio, M Edgar, R Federhen, S Feolo, M Geer, LY Helmberg, W Kapustin, Y Landsman, D Lipman, DJ Madden, TL Maglott, DR Miller, V Mizrachi, I Ostell, J Pruitt, KD Schuler, GD Sequeira, E Sherry, ST Shumway, M Sirotkin, K Souvorov, A Starchenko, G Tatusova, TA Wagner, L Yaschenko, E Ye, J AF Sayers, Eric W. Barrett, Tanya Benson, Dennis A. Bryant, Stephen H. Canese, Kathi Chetvernin, Vyacheslav Church, Deanna M. DiCuccio, Michael Edgar, Ron Federhen, Scott Feolo, Michael Geer, Lewis Y. Helmberg, Wolfgang Kapustin, Yuri Landsman, David Lipman, David J. Madden, Thomas L. Maglott, Donna R. Miller, Vadim Mizrachi, Ilene Ostell, James Pruitt, Kim D. Schuler, Gregory D. Sequeira, Edwin Sherry, Stephen T. Shumway, Martin Sirotkin, Karl Souvorov, Alexandre Starchenko, Grigory Tatusova, Tatiana A. Wagner, Lukas Yaschenko, Eugene Ye, Jian TI Database resources of the National Center for Biotechnology Information SO NUCLEIC ACIDS RESEARCH LA English DT Article ID GENE; PROTEIN; SEARCH; ENTREZ; SEQUENCES; SYSTEM; BLAST; NCBI; TOOL; SIMILARITIES 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, Entrez Gene, the NCBI Taxonomy Browser, BLAST, BLAST Link (BLink), Electronic PCR, OrfFinder, Spidey, Splign, RefSeq, UniGene, HomoloGene, ProtEST, dbMHC, dbSNP, Cancer Chromosomes, Entrez Genomes and related tools, the Map Viewer, Model Maker, Evidence Viewer, Clusters of Orthologous Groups (COGs), 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) and the PubChem suite of small molecule databases. Augmenting many of the web applications is custom implementation of the BLAST program optimized to search specialized data sets. All of the resources can be accessed through the NCBI home page at www.ncbi.nlm.nih.gov. C1 [Sayers, Eric W.; Barrett, Tanya; Benson, Dennis A.; Bryant, Stephen H.; Canese, Kathi; Chetvernin, Vyacheslav; Church, Deanna M.; DiCuccio, Michael; Edgar, Ron; Federhen, Scott; Feolo, Michael; Geer, Lewis Y.; Helmberg, Wolfgang; Kapustin, Yuri; Landsman, David; Lipman, David J.; Madden, Thomas L.; Maglott, Donna R.; Miller, Vadim; Mizrachi, Ilene; Ostell, James; Pruitt, Kim D.; Schuler, Gregory D.; Sequeira, Edwin; Sherry, Stephen T.; Shumway, Martin; Sirotkin, Karl; Souvorov, Alexandre; Starchenko, Grigory; Tatusova, Tatiana A.; Wagner, Lukas; Yaschenko, Eugene; Ye, Jian] Natl Inst Hlth, Natl Ctr Biotechnol Informat, Natl Lib Med, Bethesda, MD 20894 USA. RP Sayers, EW (reprint author), Natl Inst Hlth, Natl Ctr Biotechnol Informat, Natl Lib Med, Bldg 38A,8600 Rockville Pike, Bethesda, MD 20894 USA. EM sayers@ncbi.nlm.nih.gov RI Landsman, David/C-5923-2009; Geer, Lewis/H-2714-2014; OI Landsman, David/0000-0002-9819-6675 FU Intramural Research Program of the National Institutes of Health; National Library of Medicine FX Funding for open access charge: Intramural Research Program of the National Institutes of Health; National Library of Medicine. NR 41 TC 444 Z9 456 U1 1 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 2009 VL 37 BP D5 EP D15 DI 10.1093/nar/gkn741 PG 11 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 386TT UT WOS:000261906200002 PM 18940862 ER PT J AU Schaefer, CF Anthony, K Krupa, S Buchoff, J Day, M Hannay, T Buetow, KH AF Schaefer, Carl F. Anthony, Kira Krupa, Shiva Buchoff, Jeffrey Day, Matthew Hannay, Timo Buetow, Kenneth H. TI PID: the Pathway Interaction Database SO NUCLEIC ACIDS RESEARCH LA English DT Article ID MOLECULAR INTERACTION DATABASE; INFRASTRUCTURE; GENOMES AB The Pathway Interaction Database (PID,http://pid.nci.nih.gov) is a freely available collection of curated and peer-reviewed pathways composed of human molecular signaling and regulatory events and key cellular processes. Created in a collaboration between the US National Cancer Institute and Nature Publishing Group, the database serves as a research tool for the cancer research community and others interested in cellular pathways, such as neuroscientists, developmental biologists and immunologists. PID offers a range of search features to facilitate pathway exploration. Users can browse the predefined set of pathways or create interaction network maps centered on a single molecule or cellular process of interest. In addition, the batch query tool allows users to upload long list(s) of molecules, such as those derived from microarray experiments, and either overlay these molecules onto predefined pathways or visualize the complete molecular connectivity map. Users can also download molecule lists, citation lists and complete database content in extensible markup language (XML) and Biological Pathways Exchange (BioPAX) Level 2 format. The database is updated with new pathway content every month and supplemented by specially commissioned articles on the practical uses of other relevant online tools. C1 [Schaefer, Carl F.; Buetow, Kenneth H.] Ctr Biomed Informat & Informat Technol, Natl Canc Inst, Rockville, MD USA. [Anthony, Kira] Nat Publishing Grp, Boston, MA USA. [Krupa, Shiva] Novartis Knowledge Ctr, Cambridge, MA USA. [Buchoff, Jeffrey] SRA Int Inc, Hlth Res & Informat, Fairfax, VA USA. [Day, Matthew; Hannay, Timo] Nat Publishing Grp, London, England. RP Schaefer, CF (reprint author), Ctr Biomed Informat & Informat Technol, Natl Canc Inst, Rockville, MD USA. EM schaefec@mail.nih.gov FU National Cancer Institute FX The National Cancer Institute. Funding for open access charge: National Cancer Institute. NR 15 TC 480 Z9 489 U1 4 U2 24 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 2009 VL 37 BP D674 EP D679 DI 10.1093/nar/gkn653 PG 6 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 386TT UT WOS:000261906200120 PM 18832364 ER PT J AU Kumar, V Malhotra, SV AF Kumar, Vineet Malhotra, Sanjay V. TI IONIC LIQUID MEDIATED SYNTHESIS OF 5-HALOURACIL NUCLEOSIDES: KEY PRECURSORS FOR POTENTIAL ANTIVIRAL DRUGS SO NUCLEOSIDES NUCLEOTIDES & NUCLEIC ACIDS LA English DT Article DE Ionic liquids; antiviral; Idoxuridine; 5-halouracil nucleosides ID 5-SUBSTITUTED 2'-DEOXYURIDINES; PYRIMIDINE NUCLEOSIDES; SELECTIVE BENZOYLATION; URACIL NUCLEOSIDES; ANALOGS; DERIVATIVES; EFFICIENT; NUCLEOTIDES; METHODOLOGY; IODINATION AB Synthesis of antiviral 5-halouracil nucleosides, also used as key precursors for the synthesis of other potential antiviral drugs, has been demonstrated using ionic liquids as convenient and efficient reaction medium. C1 [Kumar, Vineet; Malhotra, Sanjay V.] NCI Frederick, SAIC Frederick, Lab Synthet Chem, Frederick, MD 21702 USA. RP Malhotra, SV (reprint author), NCI Frederick, SAIC Frederick, Lab Synthet Chem, 1050 Boyles St, Frederick, MD 21702 USA. EM malhotrasa@mail.nih.gov FU National Cancer Institute, National Institutes of Health [N01-CO-12400] 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 N01-CO-12400. The content of this publication does not necessarily reflect the views or policies of the Department of Health and Human Services, nor does mention of trade names, commercial products, or organizations imply endorsement by the U.S. Government. NR 35 TC 7 Z9 7 U1 0 U2 6 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 325 CHESTNUT ST, SUITE 800, PHILADELPHIA, PA 19106 USA SN 1525-7770 J9 NUCLEOS NUCLEOT NUCL JI Nucleosides Nucleotides Nucleic Acids PY 2009 VL 28 IS 9 BP 821 EP 834 DI 10.1080/15257770903170252 PG 14 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 500KQ UT WOS:000270298400003 PM 20183621 ER PT B AU Ross, SA AF Ross, Sharon A. BE Choi, SW Friso, S TI Nutrition, epigenetics, and cancer SO NUTRIENTS AND EPIGENETICS LA English DT Article; Book Chapter ID ASSISTED REPRODUCTIVE TECHNOLOGY; HISTONE DEACETYLASE INHIBITORS; DIETARY METHYL DEFICIENCY; TUMOR-SUPPRESSOR GENES; DIALLYL DISULFIDE; CELL-LINES; DNA METHYLATION; PROSTATE-CANCER; RAT-LIVER; IN-VIVO AB Compelling evidence suggests that diet and dietary factors are important in cancer etiology by inhibiting or enhancing the cancer process. Because diet may contribute significantly to the causation of many human cancers, it is important to uncover the molecular mechanisms of action of dietary bioactive factors in cancer prevention, as well as those stimulating neoplastic cell transformations. The role of epigenetic mechanisms in the etiology of disease, including cancer development and progression, has been increasingly recognized in recent years. The importance of epigenetic mechanisms is highlighted by their influence on gene expression and chromatin stability, which thereby impact the regulation of cell cycle control, DNA damage, apoptosis, differentiation, and other cancer-related processes. Evidence suggests that environmental factors, such as diet, may be significant regulators of epigenetic events, including DNA methylation and histone posttranslational modulation. For example, it has long been known that folate participates in the generation of S-adenosylmethionine, which acts as a methyl donor in the methylation of cytosines in DNA and participates in posttranslational methylation of histones. A classic example for the role of diet in epigenetics and cancer is the finding that dietary methyl deficiency (folate, choline, and methionine) in a rat model has been shown to alter hepatic DNA methylation patterns and induce hepatocarcinogenesis in the absence of a carcinogen. Several other bioactive food components (BFCs), including genistein, epigallocatechin gallate, diallyl disulfide, and sulforaphane have been suggested to impact epigenetic mechanisms. Many of these examples will be presented, as well as the next steps in diet, epigenetic events, and cancer prevention research. C1 NCI, NIH, US Dept HHS, Bethesda, MD 20892 USA. RP Ross, SA (reprint author), NCI, NIH, US Dept HHS, Bethesda, MD 20892 USA. NR 89 TC 2 Z9 2 U1 2 U2 4 PU CRC PRESS-TAYLOR & FRANCIS GROUP PI BOCA RATON PA 6000 BROKEN SOUND PARKWAY NW, STE 300, BOCA RATON, FL 33487-2742 USA BN 978-1-4200-6354-7 PY 2009 BP 207 EP 227 D2 10.1201/9781420063561 PG 21 WC Biochemistry & Molecular Biology; Nutrition & Dietetics SC Biochemistry & Molecular Biology; Nutrition & Dietetics GA BKK18 UT WOS:000268359800009 ER PT J AU Reynolds, MA Dawson, DR Novak, KF Ebersole, JL Gunsolley, JC Branch-Mays, GL Holt, SC Mattison, JA Ingram, DK Novak, MJ AF Reynolds, Mark A. Dawson, Dolphus R. Novak, Karen F. Ebersole, Jeffrey L. Gunsolley, John C. Branch-Mays, Grishondra L. Holt, Stanley C. Mattison, Julie A. Ingram, Donald K. Novak, M. John TI Effects of caloric restriction on inflammatory periodontal disease SO NUTRITION LA English DT Article DE Monkey; Caloric restriction; Inflammation; Periodontal disease; Sex ID REAL-TIME PCR; POLYMERASE-CHAIN-REACTION; RHESUS-MONKEYS; CARDIOVASCULAR-DISEASE; DIETARY RESTRICTION; ACTINOBACILLUS-ACTINOMYCETEMCOMITANS; NONHUMAN-PRIMATES; BACTERIA; ADULTS; RISK AB Objective: Dietary caloric restriction (CR) has been found to reduce systemic markers of inflammation and may attenuate the effects of chronic inflammatory conditions. The purpose of this study was to examine the effects of long-term CR on naturally occurring chronic inflammatory periodontal disease in a nonhuman primate model. Methods: The effects of long-term CR on extent and severity of naturally occurring chronic periodontal disease, local inflammatory and immune responses, and periodontal microbiology, were evaluated in a cohort of 81 (35 female and 46 male; 13-40 y of age) rhesus monkeys (Macaca mulatta) with no previous exposure to routine oral hygiene. CR monkeys had been subjected to 30% CR for 13-17 y relative to control-fed (CON) animals starting at 3-5 y of age. Results: Same sex CR and CON monkeys exhibited similar levels of plaque, calculus, and bleeding on probing. Among CON animals, males showed significantly greater periodontal breakdown, as reflected by higher mean clinical attachment level and periodontal probing depth scores, than females. CR males exhibited significantly less periodontal pocketing, lower IgG antibody response, and lower IL-8 and beta-glucuronidase levels compared to CON males, whereas CR females showed a lower IgG antibody response but comparable clinical parameters and inflammatory marker levels relative to CON females. Long-term CR had no demonstrable effect on the periodontal microbiota. Conclusion: Males demonstrated greater risk for naturally occurring periodontal disease than females. Long-term CR may differentially reduce the production of local inflammatory mediators and risk for inflammatory periodontal disease among males but not females. (C) 2009 Elsevier Inc. All rights reserved. C1 [Reynolds, Mark A.; Branch-Mays, Grishondra L.] Univ Maryland, Sch Dent, Dept Periodont, Baltimore, MD 21201 USA. [Dawson, Dolphus R.; Novak, Karen F.; Ebersole, Jeffrey L.; Novak, M. John] Univ Kentucky, Coll Dent, Ctr Oral Hlth Res, Lexington, KY USA. [Gunsolley, John C.] Virginia Commonwealth Univ, Sch Dent, Richmond, VA USA. [Holt, Stanley C.] Forsyth Inst, Boston, MA USA. [Mattison, Julie A.] NIA, Lab Expt Gerontol, Intramural Res Program, NIH, Baltimore, MD 21224 USA. [Ingram, Donald K.] Louisiana State Univ Syst, Pennington Biomed Res Ctr, Nutr Neurosci & Aging Lab, Baton Rouge, LA USA. RP Reynolds, MA (reprint author), Univ Maryland, Sch Dent, Dept Periodont, Baltimore, MD 21201 USA. EM mreynolds@umaryland.edu FU USPHS; National Institute of Aging [U01 AG-021406] FX This work was supported by USPHS grant U01 AG-021406 from the National Institute of Aging and by funds from the Intramural Research Program of the National Institute on Aging and the Veterinary Research Program of the Division of Research Resources of the National Institutes of Health. NR 64 TC 19 Z9 19 U1 0 U2 0 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 2009 VL 25 IS 1 BP 88 EP 97 DI 10.1016/j.nut.2008.07.003 PG 10 WC Nutrition & Dietetics SC Nutrition & Dietetics GA 383AH UT WOS:000261646000016 PM 18929461 ER PT J AU Islami, F Malekshah, AF Kimiagar, M Pourshams, A Wakefield, J Goglani, G Rakhshani, N Nasrollahzadeh, D Salahi, R Semnani, S Saadatian-Elahi, M Abnet, CC Kamangar, F Dawsey, SM Brennan, P Boffetta, P Malekzadeh, R AF Islami, Farhad Malekshah, Akbar Fazeltabar Kimiagar, Masoud Pourshams, Akram Wakefield, Jon Goglani, Goharshad Rakhshani, Nasser Nasrollahzadeh, Dariush Salahi, Rasoul Semnani, Shahryar Saadatian-Elahi, Mitra Abnet, Christian C. Kamangar, Farin Dawsey, Sanford M. Brennan, Paul Boffetta, Paolo Malekzadeh, Reza TI Patterns of Food and Nutrient Consumption in Northern Iran, a High-Risk Area for Esophageal Cancer SO NUTRITION AND CANCER-AN INTERNATIONAL JOURNAL LA English DT Article ID NORTHEASTERN IRAN; GOLESTAN COHORT; DIET AB Our objectives were to investigate patterns of food and nutrient consumption in Golestan province, a high-incidence area for esophageal cancer (EC) in northern Iran. Twelve 24-h dietary recalls were administered during a 1-yr period to 131 healthy participants in a pilot cohort study. We compare here nutrient intake in Golestan with recommended daily allowances (RDAs) and lowest threshold intakes (LTIs). We also compare the intake of 27 food groups and nutrients among several population subgroups using mean values from the 12 recalls. Rural women had a very low level of vitamin intake, which was even lower than LTIs (P < 0.01). Daily intake of vitamins A and C was lower than LTI in 67% and 73% of rural women, respectively. Among rural men, the vitamin intakes were not significantly different from LTIs. Among urban women, the vitamin intakes were significantly lower than RDAs but were significantly higher than LTIs. Among urban men, the intakes were not significantly different from RDAs. Compared to urban dwellers, intake of most food groups and nutrients, including vitamins, was significantly lower among rural dwellers. In terms of vitamin intake, no significant difference was observed between Turkmen and non-Turkmen ethnics. The severe deficiency in vitamin intake among women and rural dwellers and marked differences in nutrient intake between rural and urban dwellers may contribute to the observed epidemiological pattern of EC in Golestan, with high incidence rates among women and people with low socioeconomic status and the highest incidence rate among rural women. C1 [Islami, Farhad; Brennan, Paul; Boffetta, Paolo] Int Agcy Res Canc, F-69008 Lyon, France. [Islami, Farhad; Malekshah, Akbar Fazeltabar; Kimiagar, Masoud; Pourshams, Akram; Goglani, Goharshad; Rakhshani, Nasser; Nasrollahzadeh, Dariush; Malekzadeh, Reza] Univ Tehran Med Sci, Shariati Hosp, Digest Dis Res Ctr, Tehran, Iran. [Abnet, Christian C.; Kamangar, Farin; Dawsey, Sanford M.] Natl Canc Inst, Div Canc Epidemiol & Genet, Bethesda, MD USA. [Saadatian-Elahi, Mitra] Univ Lyon 1, F-69365 Lyon, France. [Salahi, Rasoul; Semnani, Shahryar] Golestan Univ Med Sci, Golestan Res Ctr Gastroenterol & Hepatol, Gorgan, Iran. [Islami, Farhad] Kings Coll London, Thames Canc Registry, London WC2R 2LS, England. [Malekshah, Akbar Fazeltabar; Kimiagar, Masoud] Shahid Beheshti Univ, Tehran, Iran. [Wakefield, Jon] Univ Washington, Dept Stat, Seattle, WA 98195 USA. [Wakefield, Jon] Univ Washington, Dept Biostat, Seattle, WA 98195 USA. RP Boffetta, P (reprint author), Int Agcy Res Canc, 150 Cours Albert Thomas, F-69008 Lyon, France. EM boffetta@iarc.fr RI Abnet, Christian/C-4111-2015; Semnani, Shahryar/N-2270-2016; OI Abnet, Christian/0000-0002-3008-7843; Semnani, Shahryar/0000-0002-8768-6142; Malekzadeh, Reza/0000-0003-1043-3814 FU DDRC, Iran; IARC, France; NCI, United States FX This research was supported by funds from DDRC, Iran, IARC, France, and the Intramural Research Program of the NCI, United States. We thank Dr. Hajiamin Marjani, Dr. Omid Mozaffari, and Dr. Elham Jafari for their logistic assistance. We sincerely thank our interviewers: Ailar Jamali, Anita Ramiar, Azin Kor, AkramMohamadi, Afsane Mosadegh, Halime Pourghaz, Aijamal Gorgani, Fahime Igder, Saiideh Valaee, Homeira Davoodpour and Hesam Amanbaee. We also enjoyed the close collaboration of Golestan health deputy Dr. Mohamad Naemi, Dr. Ali Aghapor, Mr. J Kabir, and Dr. Jalil Pestei, Chief of Gonbad Health District. We specially thank and appreciate Mrs Yoosefi and Mr Maramaie (local health workers of Behvarz) in the study areas. We also express appreciations to all the kind people of Gonbad for their collaboration in this study. We are deeply grateful to Dr. Nadia Slimani from IARC for her valuable comments. The authors have contributed to the manuscript by planning the study (DDRC, IARC, NNFRI), collecting data (DDRC, NNFRI, GRCGH), calculating the nutritional components (DDRC, NNFRI), analysis of data (DDRC, IARC, NCI), and preparation and revision of the manuscript (all authors). NR 23 TC 24 Z9 24 U1 1 U2 5 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 2009 VL 61 IS 4 BP 475 EP 483 DI 10.1080/01635580902803735 PG 9 WC Oncology; Nutrition & Dietetics SC Oncology; Nutrition & Dietetics GA 480LW UT WOS:000268737300007 PM 19838919 ER PT J AU Carpenter, CL Yu, MC London, SJ AF Carpenter, Catherine L. Yu, Mimi C. London, Stephanie J. TI Dietary Isothiocyanates, Glutathione S-Transferase M1 (GSTM1), and Lung Cancer Risk in African Americans and Caucasians from Los Angeles County, California SO NUTRITION AND CANCER-AN INTERNATIONAL JOURNAL LA English DT Article ID CRUCIFEROUS VEGETABLES; NEW-JERSEY; GENETIC-POLYMORPHISM; N-ACETYLCYSTEINE; VITAMIN-A; WHITE MEN; SMOKING; FRUITS; POPULATION; WOMEN AB Isothiocyanates, found in cruciferous vegetables, are anticarcinogenic. Racial differences in smoking do not fully account for the African-American excess lung cancer incidence. African Americans consume more cruciferous vegetables than U. S. Whites. Impact on lung cancer risk is unknown. The glutathione S transferase M1 (GSTM1) gene promotes urinary isothiocyanate excretion. We evaluated dietary isothiocyanates and lung cancer using a population-based case-control study of 933 African Americans and Caucasians (non-Hispanic U. S. White) from Los Angeles County, California (311 cases; 622 controls). Broccoli, cauliflower, greens, and cabbage food-frequency variables represented isothiocyanates. Isothiocyanates were protective for lung cancer risk. Adjusted odds ratio (OR) for the uppermost quartile > 80 mu mol isothiocyanates/wk, compared to lowest, was 0.65 [95% confidence interval (CI) = 0.41-1.00, trend P = 0.02]. Association was stronger among subjects with homozygous deletion of GSTM1 (OR = 0.52, 95% CI = 0.31-0.86) than subjects with at least one GSTM1 copy (OR = 0.77, 95% CI = 0.49-1.21). The difference was not statistically significant (P= 0.16). Despite African Americans consuming more cruciferous vegetables, the isothiocyanate association did not vary by race (P = 0.52). Reduced lung cancer risk with higher isothiocyanate intake may be slightly stronger among subjects with deletion of GSTM1. C1 [Carpenter, Catherine L.] Univ Calif Los Angeles, David Geffen Sch Med, Ctr Human Nutr, Los Angeles, CA 90095 USA. [Yu, Mimi C.] Univ Minnesota, Masonic Canc Ctr, Minneapolis, MN USA. [London, Stephanie J.] Natl Inst Environm Hlth Sci, Res Triangle Pk, NC USA. RP Carpenter, CL (reprint author), Univ Calif Los Angeles, David Geffen Sch Med, Ctr Human Nutr, Box 951742,12-217 Warren Hall, Los Angeles, CA 90095 USA. EM ccarpenter@mednet.ucla.edu OI London, Stephanie/0000-0003-4911-5290 FU California Tobacco Related Disease Research Program (TRDRP) [1RT-140, 3RT-403, 11IT-0082]; NCI [P01-CA42710]; National Institute of Environmental Health Sciences; National Institute of Health [ZO1 ES49017]; California Department of Health Services; National Cancer Institute's Surveillance, Epidemiology and End Results Program [N01-PC-35136]; Northern California Cancer Center [N01-PC-35139]; University of Southern California, [N02-PC-15105]; Centers for Disease Control and Prevention's National Program of Cancer Registries [CCR921930-02] FX Conduct of the case-control study performed at the University of Southern California was funded by the California Tobacco Related Disease Research Program (TRDRP) grants, 1RT-140 and 3RT-403, to Dr. London. Data analysis performed at the University of California at Los Angeles was supported by TRDRP grant 11IT-0082 to Dr. Carpenter. Dr. Carpenter was supported by NCI P01-CA42710. Dr. London is supported by the Division of Intramural Research, National Institute of Environmental Health Sciences, National Institute of Health (ZO1 ES49017). The collection of cancer incidence data used in this study was supported by the California Department of Health Services as part of the statewide cancer reporting program mandated by California Health and Safety Code Section 103885; the National Cancer Institute's Surveillance, Epidemiology and End Results Program under contract N01-PC-35136 awarded to the Northern California Cancer Center, contract N01-PC-35139 awarded to the University of Southern California, and contract N02-PC-15105 awarded to the Public Health Institute; and the Centers for Disease Control and Prevention's National Program of Cancer Registries under agreement # U55/ CCR921930-02 awarded to the Public Health Institute. The ideas and opinions expressed herein are those of the author( s), and endorsement by the State of California, Department of Health Services, the National Cancer Institute, and the Centers for Disease Control and Prevention or their contractors and subcontractors is not intended nor should be inferred. NR 49 TC 11 Z9 12 U1 0 U2 4 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 2009 VL 61 IS 4 BP 492 EP 499 DI 10.1080/01635580902752270 PG 8 WC Oncology; Nutrition & Dietetics SC Oncology; Nutrition & Dietetics GA 480LW UT WOS:000268737300009 PM 19838921 ER PT J AU Volkow, ND Wang, GJ Telang, F Fowler, JS Goldstein, RZ Alia-Klein, N Logan, J Wong, C Thanos, PK Ma, Y Pradhan, K AF Volkow, Nora D. Wang, Gene-Jack Telang, Frank Fowler, Joanna S. Goldstein, Rita Z. Alia-Klein, Nelly Logan, Jean Wong, Christopher Thanos, Panayotis K. Ma, Yemine Pradhan, Kith TI Inverse Association Between BMI and Prefrontal Metabolic Activity in Healthy Adults SO OBESITY LA English DT Article ID BODY-MASS INDEX; BRAIN DOPAMINE ACTIVITY; WORKING-MEMORY; FOLLOW-UP; IN-VIVO; OBESITY; IMPAIRMENT; DECLINE; MODEL; INDIVIDUALS AB Obesity has been associated with a higher risk for impaired cognitive function, which most likely reflects associated medical complications (i.e., cerebrovascular pathology). However, there is also evidence that in healthy individuals excess weight may adversely affect cognition (executive function, attention, and memory). Here, we measured regional brain glucose metabolism (using positron emission tomography (PET) and 2-deoxy-2[(18)F] fluoro-D-glucose (FDG)) to assess the relationship between BMI and brain metabolism (marker of brain function) in 21 healthy controls (BMI range 19-37 kg/m(2)) studied during baseline (no stimulation) and during cognitive stimulation (numerical calculations). Statistical parametric mapping (SPM) revealed a significant negative correlation between BMI and metabolic activity in prefrontal cortex (Brodmann areas 8, 9, 10, 11, 44) and cingulate gyrus (Brodmann area 32) but not in other regions. Moreover, baseline metabolism in these prefrontal regions was positively associated with performance on tests of memory (California Verbal Learning Test) and executive function (Stroop Interference and Symbol Digit Modality tests). In contrast, the regional brain changes during cognitive stimulation were not associated with BMI nor with neuropsychological performance. The observed association between higher BMI and lower baseline prefrontal metabolism may underlie the impaired performance reported in healthy obese individuals on some cognitive tests of executive function. On the other hand, the lack of an association between BMI and brain metabolic activation during cognitive stimulation indicates that BMI does not influence brain glucose utilization during cognitive performance. These results further highlight the urgency to institute public health interventions to prevent obesity. C1 [Volkow, Nora D.] NIDA, Bethesda, MD 20892 USA. [Volkow, Nora D.; Telang, Frank; Thanos, Panayotis K.; Ma, Yemine] NIAAA, Bethesda, MD USA. [Wang, Gene-Jack; Fowler, Joanna S.; Goldstein, Rita Z.; Alia-Klein, Nelly; Logan, Jean; Wong, Christopher; Pradhan, Kith] Brookhaven Natl Lab, Dept Med, Upton, NY 11973 USA. RP Volkow, ND (reprint author), NIDA, Bethesda, MD 20892 USA. EM nvolkow@nida.nih.gov OI Logan, Jean/0000-0002-6993-9994 FU NIH's Intramural Research Program (NIAAA); DOE [DE-AC01-76CH00016]; NIDA [DA06278-15] FX We thank David Schlyer, David Alexoff, Paul Vaska, Millard Jayne, Colleen Shea, Youwen Xu, Lisa Muench, Pauline Carter, Karen Apelskog, Barbara Hubbard, Thomas Maloney, Patricia Woicik, and Linda Thomas for their contributions. Research supported by NIH's Intramural Research Program (NIAAA), by DOE (DE-AC01-76CH00016), and NIDA (DA06278-15). NR 37 TC 118 Z9 118 U1 5 U2 15 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1930-7381 J9 OBESITY JI Obesity PD JAN PY 2009 VL 17 IS 1 BP 60 EP 65 DI 10.1038/oby.2008.469 PG 6 WC Endocrinology & Metabolism; Nutrition & Dietetics SC Endocrinology & Metabolism; Nutrition & Dietetics GA 389QQ UT WOS:000262110000009 PM 18948965 ER PT J AU Myslobodsky, M AF Myslobodsky, Michael TI The 'Tyranny of Choices' in the Ingestion-Controlling Network SO OBESITY FACTS LA English DT Article DE Ingestion control; Obesity; Networks; Motifs; Maximal motifs; Polypharmacy ID COMPLEX NETWORKS; SYNAPTIC PLASTICITY; DISCOVERY; MOTIFS; PROMISCUITY; PANDEMONIUM; EXPRESSION; BIOLOGY; BINDING; OBESITY AB Background: Currently used antiobesity remedies offer only a modest weight reduction, and have untoward effects that can complicate treatment efforts. Motivated by the needs of the pharmacotherapy of obesity, the study explored the role of neuropeptide Y, leptin, and corticotrophin-releasing hormone. Method: The study used Ingenuity Pathway Analysis which is a tool for automated discovery and visualization of molecular interactions. Results: In ingestion-controlling networks, neuropeptide Y, leptin, and corticotrophin-releasing hormone molecules are commonly combined into the units designated as 'maximal motifs'. The analysis of this triad allowed suggesting that maximal motifs are not more than a compendium of admission rules and transmission alternatives of their nodes catalogued in the dataset. Nonetheless, these options seem to endow them with the flexibility needed to respond dynamically as a functional unit to changing internal (metabolic) conditions or environmental challenges. Conclusion: Thus far, each peptide represents a separate target for pharmaceutical interventions (as judged by US patents scanned). The study concludes with predictions regarding designs of 'multitargeted' antiobesity agents since only by hitting a combination of targets can an appropriate therapeutic effect be achieved. C1 [Myslobodsky, Michael] NIMH, Clin Brain Disorders Branch, NIH, Bethesda, MD 20892 USA. [Myslobodsky, Michael] Howard Univ, Grad Sch, Washington, DC 20059 USA. RP Myslobodsky, M (reprint author), NIMH, Clin Brain Disorders Branch, NIH, Bethesda, MD 20892 USA. EM myslobom@mail.nih.gov FU National Institutes of Health/NIMH (CBDB) FX The author gratefully acknowledges the helpful suggestions by J. Deschenes, Ph.D. (Ingenuity Systems, CA, USA) and S. Goodman, Ph.D. (University of Pennsylvania, USA). The constructive comments of the anonymous referees and Professor Matthias Bluher helped in reshaping the arguments. This work was supported in part by the Intramural Research Program of the National Institutes of Health/NIMH (CBDB). NR 59 TC 2 Z9 2 U1 0 U2 1 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 1662-4025 J9 OBESITY FACTS JI Obes. Facts PY 2009 VL 2 IS 6 BP 374 EP 382 DI 10.1159/000260906 PG 9 WC Endocrinology & Metabolism; Nutrition & Dietetics SC Endocrinology & Metabolism; Nutrition & Dietetics GA 545PB UT WOS:000273745600008 PM 20090389 ER PT J AU Myslobodsky, M Ingraham, LJ AF Myslobodsky, Michael Ingraham, Loring J. TI Managing the Pandemic of Obesity: Siding with the Fox or the Hedgehog? SO OBESITY FACTS LA English DT Review DE Obesity; Treatment; Prevention; Public health; Cognitive therapy ID CLOCK MUTANT MICE; BODY-MASS INDEX; METABOLIC SYNDROME; EPIGENETIC MECHANISMS; DEVELOPMENTAL ORIGINS; ADIPOSE-TISSUE; ENERGY-INTAKE; FOOD-INTAKE; IMPULSIVITY; WOMEN AB Obesity is a major public health problem of pandemic proportion. Despite its high prevalence and widespread distribution (consistent with a common underlying etiology), clinical psychologists and primary care physicians routinely approach the problem with individualized but often ineffective treatments like psychotherapy and pharmacotherapy, or propose alterations to specific components of the 'toxic environment', cultural influences, and psychosocial factors purported to cause overeating. This paper presents an alternative perspective and proposes a potential framework for assisting health professionals in developing rational approaches to education about and preventive treatment of obesity based on the role of factors in early life that contribute to personality and behavior and which over time lead to obesity and its maintenance. C1 [Ingraham, Loring J.] George Washington Univ, Profess Psychol Program, Washington, DC 20052 USA. [Myslobodsky, Michael] Howard Univ, Grad Sch, Washington, DC 20059 USA. [Myslobodsky, Michael] NIMH, Clin Brain Disorders Branch, NIH, Bethesda, MD 20892 USA. RP Ingraham, LJ (reprint author), George Washington Univ, Profess Psychol Program, 1922 F St NW, Washington, DC 20052 USA. EM ingraham@gwu.edu NR 104 TC 3 Z9 3 U1 0 U2 4 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 1662-4025 J9 OBESITY FACTS JI Obes. Facts PY 2009 VL 2 IS 6 BP 384 EP 392 DI 10.1159/000261422 PG 9 WC Endocrinology & Metabolism; Nutrition & Dietetics SC Endocrinology & Metabolism; Nutrition & Dietetics GA 545PB UT WOS:000273745600009 PM 20090390 ER PT J AU Castle, PE Schiffinan, M Eeler, CM Solomon, D AF Castle, Philip E. Schiffinan, Mark Eeler, Cosette M. Solomon, Diane TI Evidence for Frequent Regression of Cervical Intraepithelial Neoplasia-Grade 2 SO OBSTETRICS AND GYNECOLOGY LA English DT Article ID 2006 CONSENSUS GUIDELINES; MILDLY ABNORMAL-CYTOLOGY; ATYPICAL SQUAMOUS-CELLS; CANCER SCREENING-TESTS; DNA-POSITIVE WOMEN; ASCUS-LSIL TRIAGE; RANDOMIZED-TRIAL; P16(INK4A) IMMUNOHISTOCHEMISTRY; UNDETERMINED SIGNIFICANCE; HUMAN PAPILLOMAVIRUSES AB OBJECTIVE: To estimate the fraction of cervical intraepithelial neoplasia 2 (CIN 2) that might regress if untreated using data from the Atypical Squamous Cells of Undetermined Significance/Low-Grade Squamous Intraepithelial Lesions Triage Study (ALTS). METHODS: We compared the cumulative occurrence of CIN 2 (n=397) and CIN 3 or more severe (n=542) diagnosed by the Pathology Quality Control Group in three trial arms-immediate colposcopy, human papillomavirus (HPV) triage, and conservative management-over the 2-year duration of the ALTS trial. A nonparametric test of trend was used to test for differences in the number of CIN 2 cases relative to number of CIN 3 or more severe cases across study arms with an increasing percentage of women referred to colposcopy at baseline. RESULTS: There were no significant differences in the cumulative 2-year cumulative CIN 3 or more severe diagnoses by study arm (10.9%, conservative management; 10.3%, HPV; 10.9%, immediate colposcopy) (P(trend)=.8), but there was a significant increase in CIN 2 diagnoses (5.8%, conservative management; 7.8%, HPV triage; 9.9%, immediate colposcopy) (P(trend)<.001) in the study arms, with increasing number of women referred to colposcopy at baseline. The relative differences in cumulative CIN 2 by study arm among women who tested HPV-16 positive at baseline were less pronounced (P(trend)=.1) than women who tested positive for other high-risk-HPV genotypes (P(trend)=.01). CONCLUSION: There was evidence that approximately 40% of undiagnosed CIN 2 will regress over 2 years, but CIN 2 caused by HPV-16 may be less likely to regress than CIN 2 caused by other high-risk-HPV genotypes. C1 [Castle, Philip E.] NCI, Div Canc Epidemiol & Genet, NIH, Dept Hlth & Human Serv, Bethesda, MD 20892 USA. NCI, Canc Prevent Div, NIH, Dept Hlth & Human Serv, Bethesda, MD 20892 USA. Univ New Mexico, Hlth Sci Ctr, Dept Mol Genet & Microbiol, Sch Med, Albuquerque, NM 87131 USA. Univ New Mexico, Hlth Sci Ctr, Dept Obstet & Gynecol, Sch Med, Albuquerque, NM 87131 USA. RP Castle, PE (reprint author), NCI, Div Canc Epidemiol & Genet, NIH, Dept Hlth & Human Serv, 6120 Execut Blvd,Room 5030,EPS MSC 7234, Bethesda, MD 20892 USA. EM castlep@mail.nih.gov FU National Cancer Institute; National Institutes of Health Department of Health [CN-55153, CN-55154, CN-55155, CN-55156, CN-55157, CN-55158, CN-55159, CN-55105] FX The Atypical Squamous Cells of Undetermined Significance/Low-Grade Squamous Intraepithelial Lesions Triage Study (ALTS) Group was supported by the National Cancer Institute, National Institutes of Health Department of Health and Human Services contracts CN-55153, CN-55154, CN-55155, CN-55156, CN-55157, CN-55158, CN-55159, and CN-55105. This research was supported in part by the Intramural Research Program of the National Institutes of Health, National Cancer Institute. Some of the equipment and supplies used in these studies Were donated or provided at reduced cost by Qiagen Corporation, Gaithersburg, MD; Cytyc Corporation, Marlborough, MA; National Testing Laboratories, Fenton, MO; Den Vu, Tucson, AZ; TriPath Imaging, Inc., Burlington, NC; and Roche Molecular Systems Inc. Alameda, CA. NR 28 TC 187 Z9 191 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 2009 VL 113 IS 1 BP 18 EP 25 PG 8 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 388KG UT WOS:000262018100005 PM 19104355 ER PT J AU Schenk, M Purdue, MP Colt, JS Hartge, P Blair, A Stewart, P Cerhan, JR De Roos, AJ Cozen, W Severson, RK AF Schenk, M. Purdue, M. P. Colt, J. S. Hartge, P. Blair, A. Stewart, P. Cerhan, J. R. De Roos, A. J. Cozen, W. Severson, R. K. TI Occupation/industry and risk of non-Hodgkin's lymphoma in the United States SO OCCUPATIONAL AND ENVIRONMENTAL MEDICINE LA English DT Article ID EPIDEMIOLOGY CONSORTIUM INTERLYMPH; MULTICENTER CASE-CONTROL; POOLED ANALYSIS; CANCER MORTALITY; FAMILY-HISTORY; EXPOSURE; WORKERS; CHEMICALS; INDUSTRY; MALIGNANCIES AB Aims: To identify occupations and industries associated with non-Hodgkin's lymphoma (NHL) in a large population-based, case-control study in the USA. Methods: Cases (n = 1189) of histologically confirmed malignant NHL ages 20-74 were prospectively identified in four geographic areas covered by the National Cancer Institute SEER Program. Controls (n = 982) were selected from the general population by random digit dialling (, 65 years of age) and from residents listed in Medicare files (65-74 years of age). Odds ratios and 95% confidence intervals for occupations and industries were calculated by unconditional logistic regression analyses, adjusting for age, gender, ethnicity and study centre. Further analyses stratified for gender and histological subtype were also performed. Results: Risk of NHL was increased for a few occupations and industries. Several white collar occupations, with no obvious hazardous exposures, had elevated risks, including purchasing agents and buyers, religious workers, physical therapists and information clerks. Occupations with excesses that may have exposures of interest include launderers and ironers, service occupations, food/beverage preparation supervisors, hand packers and packagers, roofing and siding, leather and leather products, transportation by air, nursing and personal care facilities, and specialty outpatient clinics. Significantly decreased risks of NHL were found for a number of occupations and industries including post-secondary teachers and chemical and allied products. Conclusions: The results of this study suggest that several occupations and industries may alter the risk of NHL. Our results support previously reported increased risks among farmers, printers, medical professionals, electronic workers and leather workers. These findings should be evaluated further in larger studies that have the power to focus on specific exposures and histological subtypes of NHL. C1 [Schenk, M.; Severson, R. K.] Wayne State Univ, Dept Family Med & Publ Hlth Sci, Detroit, MI 48201 USA. [Schenk, M.; Severson, R. K.] Wayne State Univ, Karmanos Canc Inst, Detroit, MI 48201 USA. [Purdue, M. P.; Colt, J. S.; Hartge, P.; Blair, A.; Stewart, P.] NCI, Div Canc Epidemiol & Genet, NIH, Dept Hlth & Human Serv, Bethesda, MD 20892 USA. [Cerhan, J. R.] Mayo Clin, Coll Med, Dept Hlth Sci Res, Rochester, MN USA. [De Roos, A. J.] Univ Washington, Fred Hutchinson Canc Res Ctr, Program Epidemiol, Seattle, WA 98195 USA. [De Roos, A. J.] Univ Washington, Dept Epidemiol, Seattle, WA 98195 USA. [Cozen, W.] Univ So Calif, Sch Med, Dept Prevent Med, Kenneth Norris Jr Comprehens Canc Ctr, Los Angeles, CA 90033 USA. RP Schenk, M (reprint author), Wayne State Univ, Dept Family Med & Publ Hlth Sci, 101 E Alexandrine, Detroit, MI 48201 USA. EM mschenk@med.wayne.edu RI Purdue, Mark/C-9228-2016; OI Purdue, Mark/0000-0003-1177-3108; Cerhan, James/0000-0002-7482-178X FU NIH (Division of Cancer Epidemiology and Genetics of the National Cancer Institute); National Cancer Institute [N01-PC-65064, N01-PC-67009, N01-CN-67008, N01-CN-67010] FX We thank Carol Haines (Westat, Rockville, Maryland) for study coordination; Laura Capece and Irish Lonn (Information Management Services, Inc., Silver Spring, Maryland) for computer support; and Barbara Rusin (Karmanos Cancer Institute), Jeanne DeWall (University of Iowa), Susan Roberts (University of Southern California), Theresa Taggart (Fred Hutchinson Cancer Research Center) for study coordination and management. Supported in part by the Intramural Research Program of the NIH (Division of Cancer Epidemiology and Genetics of the National Cancer Institute) and by National Cancer Institute SEER Contracts N01-PC-65064 (Detroit), N01-PC-67009 (Seattle), N01-CN-67008 (Iowa) and N01-CN-67010 (Los Angeles). NR 50 TC 11 Z9 11 U1 2 U2 4 PU BMJ PUBLISHING GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 1351-0711 EI 1470-7926 J9 OCCUP ENVIRON MED JI Occup. Environ. Med. PD JAN PY 2009 VL 66 IS 1 BP 23 EP 31 DI 10.1136/oem.2007.036723 PG 9 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 385SH UT WOS:000261833400006 PM 18805886 ER PT J AU Yong, LC Sigurdson, AJ Ward, EM Waters, MA Whelan, EA Petersen, MR Bhatti, P Ramsey, MJ Ron, E Tucker, JD AF Yong, L. C. Sigurdson, A. J. Ward, E. M. Waters, M. A. Whelan, E. A. Petersen, M. R. Bhatti, P. Ramsey, M. J. Ron, E. Tucker, J. D. TI Increased frequency of chromosome translocations in airline pilots with long-term flying experience SO OCCUPATIONAL AND ENVIRONMENTAL MEDICINE LA English DT Article ID COSMIC-RADIATION EXPOSURE; AIR CREW MEMBERS; IONIZING-RADIATION; CANCER-RISK; ABERRATION ANALYSIS; LYMPHOCYTES; WORKERS; DAMAGE; FISH; BIODOSIMETRY AB Background: Chromosome translocations are an established biomarker of cumulative exposure to external ionising radiation. Airline pilots are exposed to cosmic ionising radiation, but few flight crew studies have examined translocations in relation to flight experience. Methods: We determined the frequency of translocations in the peripheral blood lymphocytes of 83 airline pilots and 50 comparison subjects (mean age 47 and 46 years, respectively). Translocations were scored in an average of 1039 cell equivalents (CE) per subject using fluorescence in situ hybridisation (FISH) whole chromosome painting and expressed per 100 CE. Negative binomial regression models were used to assess the relationship between translocation frequency and exposure status and flight years, adjusting for age, diagnostic x ray procedures, and military flying. Results: There was no significant difference in the adjusted mean translocation frequency of pilots and comparison subjects (0.37 (SE 0.04) vs 0.38 (SE 0.06) translocations/100 CE, respectively). However, among pilots, the adjusted translocation frequency was significantly associated with flight years (p = 0.01) with rate ratios of 1.06 (95% CI 1.01 to 1.11) and 1.81 (95% CI 1.16 to 2.82) for a 1- and 10-year incremental increase in flight years, respectively. The adjusted rate ratio for pilots in the highest compared to the lowest quartile of flight years was 2.59 (95% CI 1.26 to 5.33). Conclusions: Our data suggests that pilots with long-term flying experience may be exposed to biologically significant doses of ionising radiation. Epidemiological studies with longer follow-up of larger cohorts of pilots with a wide range of radiation exposure levels are needed to clarify the relationship between cosmic radiation exposure and cancer risk. C1 [Yong, L. C.; Waters, M. A.; Whelan, E. A.; Petersen, M. R.] NIOSH, Industrywide Studies Branch, Div Surveillance Hazard Evaluat & Field Studies, Cincinnati, OH 45226 USA. [Sigurdson, A. J.; Bhatti, P.; Ron, E.] NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. [Ward, E. M.] Amer Canc Soc, Dept Epidemiol & Surveillance Res, Atlanta, GA 30329 USA. [Ramsey, M. J.] Lawrence Livermore Natl Lab, Livermore, CA USA. [Tucker, J. D.] Wayne State Univ, Dept Biol Sci, Detroit, MI 48202 USA. RP Yong, LC (reprint author), NIOSH, Industrywide Studies Branch, Div Surveillance Hazard Evaluat & Field Studies, 4676 Columbia Pkwy,R-15, Cincinnati, OH 45226 USA. EM LAY7@CDC.GOV RI Waters, Martha/B-7441-2011 FU National Institute for Occupational Safety and Health and the National Cancer Institute [Y1CP802904]; Intramural Research Program of the Division of Cancer Epidemiology and Genetics, National Cancer Institute FX This research was supported in part by an interagency agreement between the National Institute for Occupational Safety and Health and the National Cancer Institute contract Y1CP802904 and by the Intramural Research Program of the Division of Cancer Epidemiology and Genetics, National Cancer Institute. Work was performed in part under the auspices of the U. S. DOE by the Lawrence Livermore National Laboratory under contract no. W-7405-ENG-48. NR 40 TC 27 Z9 28 U1 2 U2 13 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 2009 VL 66 IS 1 BP 56 EP 62 DI 10.1136/oem.2008.038901 PG 7 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 385SH UT WOS:000261833400011 PM 19074211 ER PT J AU Koutros, S Baris, D Bell, E Zheng, T Zhang, Y Holford, TR Leaderer, BP Landgren, O Zahm, SH AF Koutros, S. Baris, D. Bell, E. Zheng, T. Zhang, Y. Holford, T. R. Leaderer, B. P. Landgren, O. Zahm, S. Hoar TI Use of hair colouring products and risk of multiple myeloma among US women SO OCCUPATIONAL AND ENVIRONMENTAL MEDICINE LA English DT Article ID DYE USE; UNITED-STATES; CONNECTICUT; LEUKEMIA; LYMPHOMA; CANCERS AB Objective: To evaluate the association between personal hair dye use and risk of multiple myeloma among women. Methods: A population-based case-control study of 175 cases of multiple myeloma and 679 controls. Cases and controls were interviewed regarding the type and colour of hair colouring product used, age at first use, age use stopped, duration, and the frequency of use per year. Odds ratios (ORs) and 95% confidence intervals (CI) were estimated using unconditional logistic regression to compare never users with four exposure groups: all users, ever semi-permanent dye users, ever permanent dye users and dark permanent dye users (most frequent use). Results: No association was found between ever reporting hair colouring product use and myeloma risk among all users (OR 0.8; 95% CI 0.5 to 1.1), semipermanent dye users (OR 0.7; 95% CI 0.4 to 1.2), permanent dye users (OR 0.8; 95% CI 0.5 to 1.1) or dark permanent dye users (OR 0.8; 95% CI 0.5 to 1.3). There were no significant associations among women who used hair dyes before 30 years of age, started use before 1980, had >= 240 lifetime applications, or had used dark permanent dye for 28 or more years. Conclusion: No evidence of an association between hair colouring product use and myeloma risk was found. However, given the conflicting body of literature on hair colouring product use and risk of multiple myeloma, this question should be further evaluated in larger studies or consortia, and in high risk groups. C1 [Koutros, S.; Baris, D.; Landgren, O.; Zahm, S. Hoar] NCI, Div Canc Epidemiol & Genet, NIH, DHHS, Rockville, MD 20852 USA. [Bell, E.] SUNY Albany, Sch Publ Hlth, Dept Epidemiol, New York, NY USA. [Zheng, T.; Zhang, Y.; Holford, T. R.; Leaderer, B. P.] Yale Univ, Sch Med, Dept Epidemiol & Publ Hlth, New Haven, CT 06510 USA. RP Koutros, S (reprint author), NCI, Div Canc Epidemiol & Genet, NIH, DHHS, 6120 Execut Blvd,EPS 8122, Rockville, MD 20852 USA. EM Koutross@mail.nih.gov FU Intramural Research Program of the National Institutes of Health FX This research was supported by the Intramural Research Program of the National Institutes of Health (National Cancer Institute, Division of Cancer Epidemiology and Genetics). Certain data used in the study were obtained from the Connecticut Tumor Registry, Connecticut Department of Public Health. The authors thank the institutions that allowed access to diagnostic materials and pathology reports, including the following hospitals: Charlotte Hungerford Hospital, Danbury Hospital, Greenwich Hospital, Griffin Hospital, Hartford Hospital, Johnson Memorial Hospital, Middlesex Hospital, Lawrence and Memorial Hospital, New Britain General Hospital, Bradley Memorial Hospital, Norwalk Hospital, St. Francis Hospital and Medical Center, St. Mary's Hospital, Hospital of St. Raphael, St. Vincent's Medical Center, Stamford Hospital, William W. Backus Hospital, Waterbury Hospital, Yale-New Haven Hospital, Manchester Memorial Hospital, Rockville General Hospital, Bridgeport Hospital, Windham Hospital, Sharon Hospital, Milford Hospital, New Milford Hospital, Bristol Hospital, MidState Medical Center and Day-Kimball Hospital. NR 17 TC 6 Z9 6 U1 2 U2 7 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 2009 VL 66 IS 1 BP 68 EP 70 DI 10.1136/oem.2008.041053 PG 3 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 385SH UT WOS:000261833400013 PM 18805876 ER PT J AU Levy-Clarke, G Goodglick, T Ding, XY Byrnes, G Gangaputra, S Nussenblatt, R Chan, CC Yeh, S AF Levy-Clarke, Grace Goodglick, Todd Ding, Xiaoyan Byrnes, Gordon Gangaputra, Sapna Nussenblatt, Robert Chan, Chi-Chao Yeh, Steven TI Recalcitrant Granulomatous Sclerouveitis in a Patient with Granulomatous ANCA-associated Vasculitis SO OCULAR IMMUNOLOGY AND INFLAMMATION LA English DT Article DE ANCA-associated granulomatous vasculitis; necrotizing scleritis; sclero-choroiditis; Wegener granulomatosis ID WEGENERS-GRANULOMATOSIS AB Purpose: To report an unusual case of granulomatous sclerochoroiditis. Design: Interventional case report. Methods: A patient with ANCA-associated granulomatous vasculitis presented with nodular necrotizing scleritis, which was recalcitrant to multiple systemic immunosuppressive therapies and progressed to a blind painful eye, which was enucleated. Results: Histopathology revealed extensive occlusive vasculitis, diffuse T- and B- cellular infiltration, and lymphoid granulomatous formation. Enhanced MHC class II antigens, adhesion molecules, and Fas (CD95) and FasL (CD95L) were detected in the lesion. Conclusion: Granulomatous sclerochoroiditis with aggressive immune reaction can be a complication of ANCA-associated granulomatous vasculitis. C1 [Levy-Clarke, Grace] St Lukes Cataract & Laser Ctr, St Petersburg, FL 33702 USA. [Goodglick, Todd] Washington Eye Physicians, Chevy Chase, MD USA. [Ding, Xiaoyan; Nussenblatt, Robert; Chan, Chi-Chao; Yeh, Steven] NEI, Immunol Lab, NIH, Bethesda, MD 20892 USA. [Byrnes, Gordon] Retina Grp Washington, Chevy Chase, MD USA. [Gangaputra, Sapna] Univ Wisconsin, Fundus Photograph Reading Ctr, Madison, WI USA. RP Levy-Clarke, G (reprint author), St Lukes Cataract & Laser Ctr, St Petersburg, FL 33702 USA. EM gclarke@stlukeseye.com FU Intramural NIH HHS [Z01 EY000222-22] NR 5 TC 5 Z9 5 U1 0 U2 0 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 325 CHESTNUT ST, SUITE 800, PHILADELPHIA, PA 19106 USA SN 0927-3948 J9 OCUL IMMUNOL INFLAMM JI Ocul. Immunol. Inflamm. PY 2009 VL 17 IS 2 BP 83 EP 87 AR PII 910915887 DI 10.1080/09273940802596500 PG 5 WC Ophthalmology SC Ophthalmology GA 439WO UT WOS:000265658500004 PM 19412867 ER PT J AU Sen, HN Bodaghi, B Le Hoang, P Nussenblatt, R AF Sen, H. Nida Bodaghi, Bahram Le Hoang, Phuc Nussenblatt, Robert TI Primary Intraocular Lymphoma: Diagnosis and Differential Diagnosis SO OCULAR IMMUNOLOGY AND INFLAMMATION LA English DT Article DE intraocular lymphoma; diagnosis; cytology; cytokines; immunohistochemistry ID RETICULUM-CELL SARCOMA; NERVOUS-SYSTEM LYMPHOMA; POLYMERASE-CHAIN-REACTION; CLINICAL-FEATURES; POSTERIOR UVEITIS; OCULAR LYMPHOMA; FLOW-CYTOMETRY; VITREOUS CELLS; BIOPSY; VITRECTOMY AB Diagnosis of PIOL can be challenging. It requires a high degree of clinical suspicion and differential diagnosis includes infectious and non-infectious etiologies particularly the common masquaraders sarcoidosis, tuberculosis, viral retinitis and syphilis. The definitive diagnosis depends on demonstration of malignant lymphoma cells in ocular specimens or CSF. Ocular specimen could include vitreous, aqueous or chorioretinal biopsy. Ocular pathologist should be consulted prior to the diagnostic procedure to help handle and process the specimen appropriately. In addition to cytology, flow cytometry, immunohistochemistry, molecular analysis and cytokines may be used as adjuncts in facilitating the diagnosis. C1 [Sen, H. Nida; Nussenblatt, Robert] NEI, NIH, Bethesda, MD 20892 USA. [Bodaghi, Bahram; Le Hoang, Phuc] Univ Paris 06, Dept Ophthalmol, Pitie Salpetriere Hosp, Paris, France. RP Sen, HN (reprint author), NEI, NIH, 10 Ctr Dr Bldg 10 Rm 10N112, Bethesda, MD 20892 USA. EM senh@nei.nih.gov FU Intramural NIH HHS [Z99 EY999999] NR 56 TC 24 Z9 27 U1 0 U2 0 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 325 CHESTNUT ST, SUITE 800, PHILADELPHIA, PA 19106 USA SN 0927-3948 J9 OCUL IMMUNOL INFLAMM JI Ocul. Immunol. Inflamm. PY 2009 VL 17 IS 3 BP 133 EP 141 AR PII 912966575 DI 10.1080/09273940903108544 PG 9 WC Ophthalmology SC Ophthalmology GA 467TZ UT WOS:000267767300001 PM 19585354 ER PT J AU Coupland, SE Chan, CC Smith, J AF Coupland, Sarah E. Chan, Chi Chao Smith, Justine TI Pathophysiology of Retinal Lymphoma SO OCULAR IMMUNOLOGY AND INFLAMMATION LA English DT Article DE retinal lymphoma; vitreoretinal lymphoma; vitreal lymphoma; intraocular lymphoma; IOL; PCNSL; DLBCL ID PRIMARY INTRAOCULAR LYMPHOMA; B-CELL-LYMPHOMA; CENTRAL-NERVOUS-SYSTEM; INTERLEUKIN-10 GENE POLYMORPHISMS; INTRAVITREAL METHOTREXATE; MOLECULAR DIAGNOSIS; CHEMOKINE RECEPTORS; CYTOKINE PRODUCTION; OUTCOME PREDICTION; TISSUE MICROARRAY AB Retinal lymphoma, the most common form of intraocular lymphoma, is a high-grade malignancy, usually of B-cell type, and is associated with a poor prognosis because of frequent central nervous system (CNS) involvement. The neoplastic B-cells of retinal lymphoma have a characteristic morphology and immunophenotype, express certain chemokines and chemokine receptors, and produce interleukins (IL), e.g. IL-10. Together with the cytological features of these tumors, the immunophenotype, presence of immunoglobulin rearrangements, and biochemical profile aid the diagnosis of retinal lymphomas. Immunophenotyping and somatic mutation analysis suggest derivation of most retinal lymphomas from an early post-germinal centre B-cell. Chromosomal translocation data would suggest, however, that a subgroup of these neoplasms may arise from germinal centre B-cells, and these could be associated with a better prognosis. Further investigations, such as gene expression profiling, are required to identify oncogenic pathways potentially involved in retinal lymphoma development, and to identify new prognostic/therapeutic markers for this tumor. C1 [Coupland, Sarah E.] Univ Liverpool, Dept Cellular & Mol Pathol, Liverpool L69 3GA, Merseyside, England. [Chan, Chi Chao] NEI, Immunopathol Sect, Immunol Lab, NIH, Bethesda, MD 20892 USA. [Smith, Justine] Oregon Hlth & Sci Univ, Casey Eye Inst, Portland, OR 97201 USA. [Smith, Justine] Oregon Hlth & Sci Univ, Dept Cell & Dev Biol, Portland, OR 97201 USA. RP Coupland, SE (reprint author), Univ Liverpool, Dept Pathol, Duncan Bldg,Daulby St, Liverpool L69 3GA, Merseyside, England. EM s.e.coupland@liverpool.ac.uk FU Research to Prevent Blindness; Schnitzer-Novack Foundation; ENI Intramural Research Program; Eye Tumour Research Fund; Royal Liverpool University Hospital, UK FX Dr Justine Smith acknowledges support from Research to Prevent Blindness (unrestricted grant to Casey Eye Institute) and the Schnitzer-Novack Foundation. Dr Chi-Chao Chan acknowledges support from the ENI Intramural Research Program. Dr Sarah Coupland would like to acknowledge the generous support of the Eye Tumour Research Fund, Royal Liverpool University Hospital, UK. She would also like to express her gratitude to Professor Bertil Damato (Royal Liverpool University Hospital) for the discussions about the manuscript. All authors would also like to thank Dr Nathalie Cassoux and Professor Phuc LeHoang (Department of Ophthalmology, Pitie-Salpetriere Hospital, University Paris VI, Paris, France) for the provision of the clinical photographs. NR 90 TC 28 Z9 30 U1 0 U2 1 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 325 CHESTNUT ST, SUITE 800, PHILADELPHIA, PA 19106 USA SN 0927-3948 J9 OCUL IMMUNOL INFLAMM JI Ocul. Immunol. Inflamm. PY 2009 VL 17 IS 4 BP 227 EP 237 AR PII 913569367 DI 10.1080/09273940903168696 PG 11 WC Ophthalmology SC Ophthalmology GA 480FF UT WOS:000268717000001 PM 19657975 ER PT J AU Tang, J Fillmore, G Nussenblatt, RB AF Tang, Johnny Fillmore, Gary Nussenblatt, Robert B. TI Antiphospholipid Antibody Syndrome Mimicking Serpiginous Choroidopathy SO OCULAR IMMUNOLOGY AND INFLAMMATION LA English DT Article DE antiphospholipid antibody syndrome (Hughes Syndrome); serpiginous retino choroidopathy treatment; indocyanine green angiography; fluorescein angiography AB Purpose: To report a patient with antiphospholipid antibody syndrome (APS) presenting with ocular findings similar to serpiginous choroidopathy. Methods: Case report. Results: A man complained of blurred vision. Examination revealed vitritis, vasculitis, retinal ischemia, and neovascularization. Clinical and angiographic features consistent with serpiginous choroidopathy were found. An evaluation for uveitis and retinal vasculitis was remarkable for APS. Conclusion: This case expands on previously reported ocular findings associated with APS. Although the role of antiphospholipid antibodies in the pathogenesis remains undefined, the findings, including the serpiginous-like choroidopathy, can be reasonably explained by vaso-occlusion in both the retinal and choroidal vasculature. C1 [Tang, Johnny] Case Western Reserve Univ, Univ Hosp, Inst Eye, Cleveland, OH 44106 USA. [Tang, Johnny] Louis Stokes Cleveland DVA Med Ctr, Res Serv, Cleveland, OH USA. [Tang, Johnny] Univ Hosp, Case Med Ctr, Cleveland, OH USA. [Fillmore, Gary] Eye Consultants, Spokane, WA USA. [Nussenblatt, Robert B.] NEI, Immunol Lab, NIH, Bethesda, MD 20892 USA. RP Tang, J (reprint author), Case Western Reserve Univ, Univ Hosp, Inst Eye, LKSD 4107 11100 Euclid Ave, Cleveland, OH 44106 USA. EM bostonretina@aol.com FU Department of Veteran's Affairs; Rehabilitation Research & Development Career Development Award; Research to Prevent Blindness; Lions Club of Cleveland; NIH FX This work was supported by funding from the Department of Veteran's Affairs, Rehabilitation Research & Development Career Development Award, Research to Prevent Blindness, Lions Club of Cleveland, NIH Core Grant and, in part, by the Intramural Research Program of the National Institutes of Health. NR 6 TC 3 Z9 3 U1 0 U2 0 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 325 CHESTNUT ST, SUITE 800, PHILADELPHIA, PA 19106 USA SN 0927-3948 J9 OCUL IMMUNOL INFLAMM JI Ocul. Immunol. Inflamm. PY 2009 VL 17 IS 4 BP 278 EP 281 AR PII 913569175 DI 10.1080/09273940902989340 PG 4 WC Ophthalmology SC Ophthalmology GA 480FF UT WOS:000268717000009 PM 19657983 ER PT S AU Klinman, DM Tross, D Klaschik, S Shirota, H Sato, T AF Klinman, Dennis M. Tross, Debbie Klaschik, Sven Shirota, Hidekazu Sato, Takeshi BE Rossi, JJ Gait, MJ Eckstein, F TI Therapeutic Applications and Mechanisms Underlying the Activity of Immunosuppressive Oligonucleotides SO OLIGONUCLEOTIDE THERAPEUTICS SE ANNALS OF THE NEW YORK ACADEMY OF SCIENCES LA English DT Article; Proceedings Paper CT 4th Annual Meeting of the Oligonucleotide-Therapeutics-Society CY OCT 15-18, 2008 CL Harvard Med Sch, Boston, MA HO Harvard Med Sch DE oligonucleotide; suppressive; therapy; autoimmunity; inflammation ID INDUCED PULMONARY INFLAMMATION; 4TH INTERNATIONAL WORKSHOP; INDUCED IMMUNE ACTIVATION; SUPPRESSIVE OLIGODEOXYNUCLEOTIDES; INTERFERON-GAMMA; BACTERIAL-DNA; REACTIVE ARTHRITIS; ENDOTOXIC-SHOCK; MURINE; MICE AB Synthetic oligodeoxynucleotides (ODN) capable of "neutralizing" or "inhibiting" immune responses have been described. This review will focus on the properties of phosphorothioate ODN that mimic the immunosuppressive activity of the repetitive TTAGGG motifs present in mammalian telomeres. These TTAGGG multimers block the production of pro-inflammatory and T helper type 1 cytokines elicited when immune cells are activated by a wide variety of Toll-like receptor ligands, polyclonal activators, and antigens. Several mechanisms contribute to the suppressive activity of such ODN. Ongoing microarray studies indicate that suppressive ODN interfere with the phosphorylation of signal transducer and activator of transcription I (STATI) and STAT4, thereby blocking the inflammation mediated by STAT-associated signaling cascades. In animal models, suppressive ODN can be used to prevent or treat diseases characterized by persistent immune activation, including collagen-induced arthritis, inflammatory arthritis, systemic lupus erythematosus, silicosis, and toxic shock. These findings suggest that TTAGGG multimers may find broad use in the treatment of diseases characterized by over-exuberant/persistent immune activation. C1 [Klinman, Dennis M.; Tross, Debbie; Klaschik, Sven; Shirota, Hidekazu; Sato, Takeshi] NCI, Canc & Inflammat Program, Frederick, MD 21702 USA. RP Klinman, DM (reprint author), NCI, Canc & Inflammat Program, Bldg 567,Rm 205, Frederick, MD 21702 USA. EM klinmand@mail.nih.gov NR 50 TC 24 Z9 26 U1 0 U2 3 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXEN, ENGLAND SN 0077-8923 BN 978-1-57331-758-0 J9 ANN NY ACAD SCI JI Ann.NY Acad.Sci. PY 2009 VL 1175 BP 80 EP 88 DI 10.1111/j.1749-6632.2009.04970.x PG 9 WC Medicine, Research & Experimental; Multidisciplinary Sciences SC Research & Experimental Medicine; Science & Technology - Other Topics GA BLQ41 UT WOS:000270798600009 PM 19796080 ER PT J AU Raafat, A Lawson, S Bargo, S Klauzinska, M Strizzi, L Goldhar, AS Buono, K Salomon, D Vonderhaar, BK Callahan, R AF Raafat, A. Lawson, S. Bargo, S. Klauzinska, M. Strizzi, L. Goldhar, A. S. Buono, K. Salomon, D. Vonderhaar, B. K. Callahan, R. TI Rbpj conditional knockout reveals distinct functions of Notch4/Int3 in mammary gland development and tumorigenesis SO ONCOGENE LA English DT Article DE RBP-J; Int3; tumorigenesis ID TRUNCATED INT3 GENE; NEOPLASTIC TRANSFORMATION; CELL-DIFFERENTIATION; NOTCH; ACTIVATION; TUMOR; EXPRESSION; EPITHELIUM; SUPPRESSOR; HAIRLESS AB Transgenic mice expressing the Notch 4 intracellular domain (ICD) (Int3) in the mammary gland have two phenotypes: arrest of mammary alveolar/lobular development and mammary tumorigenesis. Notch4 signaling is mediated primarily through the interaction of Int3 with the transcription repressor/activator Rbpj. We have conditionally ablated the Rbpj gene in the mammary glands of mice expressing whey acidic protein (Wap)-Int3. Interestingly, Rbpj knockout mice (Wap-Cre(+)/Rbpj(-/-)/Wap-Int3) have normal mammary gland development, suggesting that the effect of endogenous Notch signaling on mammary gland development is complete by day 15 of pregnancy. RBP-J heterozygous (Wap-Cre(+)/Rbpj(-/-)/Wap-Int3) and Rbpj control (Rbpj(flox/flox)/Wap-Int3) mice are phenotypically the same as Wap-Int3 mice with respect to mammary gland development and tumorigenesis. In addition, the Wap-Cre(+)/Rbpj(-/-)/Wap-Int3- knockout mice also developed mammary tumors at a frequency similar to Rbpj heterozygous and Wap-Int3 control mice but with a slightly longer latency. Thus, the effect on mammary gland development is dependent on the interaction of the Notch ICD with the transcription repressor/activator Rbpj, and Notch-induced mammary tumor development is independent of this interaction. C1 [Raafat, A.; Lawson, S.; Bargo, S.; Klauzinska, M.; Strizzi, L.; Goldhar, A. S.; Salomon, D.; Vonderhaar, B. K.; Callahan, R.] NCI, Mammary Biol & Tumorigenesis Lab, NIH, Bethesda, MD 20892 USA. [Buono, K.] NIDDKD, Lab Genet & Physiol, NIH, Bethesda, MD 20892 USA. RP Callahan, R (reprint author), NCI, Mammary Biol & Tumorigenesis Lab, NIH, 37 Convent Dr,Bldg 37,Room 1118A, Bethesda, MD 20892 USA. EM rc54d@nih.gov FU NIH; National Cancer Institute; Center for Cancer Research FX The Rbpjflox/flox mice were kindly provided by Dr Tasuku Honjo, Department of Medical Chemistry, Graduate School of Medicine, Kyoto University, Kyoto, Japan, and the WAP-Cre mice were kindly provided by Dr Lothar Hennighausen, Laboratory of Genetics and Physiology, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD, USA. This research was supported by the Intramural Research Program of the NIH, National Cancer Institute, Center for Cancer Research. NR 32 TC 30 Z9 30 U1 0 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 2009 VL 28 IS 2 BP 219 EP 230 DI 10.1038/onc.2008.379 PG 12 WC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity GA 395CY UT WOS:000262501100006 PM 18836481 ER PT J AU Kim, SY Toretsky, JA Scher, D Helman, LJ AF Kim, Su Young Toretsky, Jeffrey A. Scher, Daniel Helman, Lee J. TI The Role of IGF-1R in Pediatric Malignancies SO ONCOLOGIST LA English DT Article DE IGF-1R; Pediatric malignancy; Molecular targeting; Therapeutic antibody ID GROWTH-FACTOR-I; GASTROINTESTINAL STROMAL TUMORS; EWINGS-SARCOMA; WILMS-TUMOR; AUTOCRINE GROWTH; FACTOR RECEPTOR; METASTATIC OSTEOSARCOMA; MONOCLONAL-ANTIBODIES; SIGNAL-TRANSDUCTION; GLIOBLASTOMA CELLS AB The insulin-like growth factor (IGF) family consists of ligands (IGF-I, IGF-II, insulin), several receptors (including IGF-1R), and six binding proteins (IGFBP-1 through IGFBP-6). Members of this family regulate key cellular activities and they also play an important role in the development and progression of both adult and childhood cancers. Binding of a ligand to the receptor leads to its activation, followed by signal transduction along several pathways. In some childhood malignancies, IGF-1R can be activated by endocrine, autocrine, or paracrine mechanisms. Although mutations in IGF-1R have not been identified, this signaling pathway is upregulated in many childhood cancers. These findings have led to the development of a host of IGF-1R signaling modulators that are currently being tested in clinical trials. This review explores the role of IGF-1R in a range of childhood malignancies. The Oncologist 2009; 14: 83-91 C1 [Kim, Su Young; Helman, Lee J.] NCI, Ctr Canc Res, Pediat Oncol Branch, NIH, Bethesda, MD 20892 USA. [Toretsky, Jeffrey A.; Scher, Daniel] Georgetown Univ, Sch Med, Lombardi Comprehens Canc Ctr, Washington, DC USA. RP Kim, SY (reprint author), NCI, Ctr Canc Res, Pediat Oncol Branch, NIH, 10 Ctr Dr,Bldg 10,CRC 1W-3750, Bethesda, MD 20892 USA. EM kimsuyou@mail.nih.gov FU Intramural NIH HHS [Z99 CA999999]; NCI NIH HHS [R01 CA088004, R01 CA088004-08] NR 70 TC 60 Z9 62 U1 0 U2 1 PU ALPHAMED PRESS PI DURHAM PA 318 BLACKWELL ST, STE 260, DURHAM, NC 27701-2884 USA SN 1083-7159 EI 1549-490X J9 ONCOLOGIST JI Oncologist PD JAN PY 2009 VL 14 IS 1 BP 83 EP 91 DI 10.1634/theoncologist.2008-0189 PG 9 WC Oncology SC Oncology GA 407MJ UT WOS:000263368100011 PM 19126579 ER PT J AU Doroshow, JH Croyle, RT Niederhuber, JE AF Doroshow, James H. Croyle, Robert T. Niederhuber, John E. TI Five Strategies for Accelerating the War on Cancer in an Era of Budget Deficits SO ONCOLOGIST LA English DT Editorial Material ID CLINICAL-TRIALS; POLICY CHANGE; DISPARITIES; ENROLLMENT; US AB In recent years, the National Institutes of Health's largest institute, the National Cancer Institute (NCI), has adapted to difficult economic conditions by leveraging its robust infrastructure - which includes risk factor surveillance and population monitoring, research centers (focused on basic, translation, clinical, and behavioral sciences), clinical trials and health care research networks, and rigorously validated statistical models - to maximize the impact of scientific progress on the public health. To continue advancement and realize the opportunity of significant, population-level changes in cancer mortality, the NCI recommends that five national-level actions be taken: (1) significantly increase enrollment of Medicare patients into cancer clinical trials through adequate physician reimbursement, (2) increase NCI/Centers for Medicare and Medicaid Services collaboration on clinical trials research to evaluate the therapeutic efficacy of anticancer drugs, (3) establish a national outcomes research demonstration project to test strategies for measuring and improving health care quality and provide an evidence base for public policy, (4) leverage existing tobacco-control collaborations and possible new authorities at the U. S. Food and Drug Administration to realize the outstanding health gains possible from a reduction in tobacco use, and (5) increase colorectal cancer screening rates though intensified collaboration between federal agencies working to address barriers to access and use of screening. These cost-effective strategies provide the opportunity for extraordinary results in an era of budget deficits. Of the chronic diseases, cancer has the strongest national research infrastructure that can be leveraged to produce rapid results to inform budget prioritization and public policy, as well as mobilize new projects to answer critical public health questions. The Oncologist 2009; 14: 110-116 C1 [Doroshow, James H.; Croyle, Robert T.; Niederhuber, John E.] NCI, Bethesda, MD 20892 USA. RP Doroshow, JH (reprint author), NCI, 31 Ctr Dr,Room 3A44, Bethesda, MD 20892 USA. EM doroshoj@mail.nih.gov NR 20 TC 3 Z9 3 U1 0 U2 1 PU ALPHAMED PRESS PI DURHAM PA 318 BLACKWELL ST, STE 260, DURHAM, NC 27701-2884 USA SN 1083-7159 EI 1549-490X J9 ONCOLOGIST JI Oncologist PY 2009 VL 14 IS 2 BP 110 EP 116 DI 10.1634/theoncologist.2008-0270 PG 7 WC Oncology SC Oncology GA 417ZD UT WOS:000264116100002 PM 19147688 ER PT J AU Niederhuber, JE AF Niederhuber, John E. TI Facilitating Patient-Centered Cancer Research and a New Era of Drug Discovery SO ONCOLOGIST LA English DT Editorial Material C1 [Niederhuber, John E.] NCI, Bethesda, MD 20892 USA. RP Niederhuber, JE (reprint author), Care of Lubenow A E, NCI, MPH, Off Commun, Bldg 31,Room 11A27,31 Ctr Dr,MSC 2580, Bethesda, MD 20892 USA. EM lubenowa@occ.nci.nih.gov NR 0 TC 2 Z9 2 U1 0 U2 0 PU ALPHAMED PRESS PI DURHAM PA 318 BLACKWELL ST, STE 260, DURHAM, NC 27701-2884 USA SN 1083-7159 J9 ONCOLOGIST JI Oncologist PY 2009 VL 14 IS 4 BP 311 EP 312 DI 10.1634/theoncologist.2009-0051 PG 2 WC Oncology SC Oncology GA 439QD UT WOS:000265641200002 PM 19365096 ER PT J AU Bates, SE Benz, EJ AF Bates, Susan E. Benz, Edward J., Jr. TI Troublesome Words, Linguistic Precision, and Medical Oncology SO ONCOLOGIST LA English DT Editorial Material C1 [Bates, Susan E.] NCI, Med Oncol Branch, Ctr Canc Res, Bethesda, MD 20892 USA. [Benz, Edward J., Jr.] Dana Farber Canc Inst, Boston, MA 02115 USA. RP Bates, SE (reprint author), NCI, Med Oncol Branch, Ctr Canc Res, Bldg 10,Room 12N226,MSC 1903,9000 Rockville Pike, Bethesda, MD 20892 USA. EM sebates@helix.nih.gov FU Intramural NIH HHS; PHS HHS [0] NR 14 TC 1 Z9 1 U1 0 U2 0 PU ALPHAMED PRESS PI DURHAM PA 318 BLACKWELL ST, STE 260, DURHAM, NC 27701-2884 USA SN 1083-7159 J9 ONCOLOGIST JI Oncologist PY 2009 VL 14 IS 4 BP 445 EP 447 DI 10.1634/theoncologist.2008-0253 PG 3 WC Oncology SC Oncology GA 439QD UT WOS:000265641200013 PM 19357227 ER PT J AU Trimble, EL Mccaskill-Stevens, W Denicoff, A Minig, L Minasian, LM AF Trimble, Edward L. Mccaskill-Stevens, Worta Denicoff, Andrea Minig, Lucas Minasian, Lori M. TI Learning from Experience SO ONCOLOGIST LA English DT Article C1 [Trimble, Edward L.; Mccaskill-Stevens, Worta; Denicoff, Andrea; Minig, Lucas; Minasian, Lori M.] NCI, Bethesda, MD 20892 USA. RP Trimble, EL (reprint author), NCI, 6130 Execut Blvd,Suite 7025,MSC 7436, Bethesda, MD 20892 USA. EM trimblet@mail.nih.gov NR 1 TC 0 Z9 0 U1 0 U2 1 PU ALPHAMED PRESS PI DURHAM PA 318 BLACKWELL ST, STE 260, DURHAM, NC 27701-2884 USA SN 1083-7159 J9 ONCOLOGIST JI Oncologist PY 2009 VL 14 IS 5 BP 476 EP 477 DI 10.1634/theoncologist.2009-0073 PG 2 WC Oncology SC Oncology GA 448WV UT WOS:000266293600004 PM 19417099 ER PT J AU Chuk, MK Balis, FM Fox, E AF Chuk, Meredith K. Balis, Frank M. Fox, Elizabeth TI Trabectedin SO ONCOLOGIST LA English DT Review DE Trabectedin; DNA repair; Drug profile ID SOFT-TISSUE SARCOMA; CONTINUOUS INTRAVENOUS-INFUSION; MARINE ANTICANCER DRUG; DNA-REPAIR PATHWAYS; PHASE-I; ECTEINASCIDIN-743 ET-743; HOMOLOGOUS RECOMBINATION; NUCLEOTIDE-EXCISION; SOLID TUMORS; MOLECULAR-MECHANISMS C1 [Chuk, Meredith K.; Balis, Frank M.; Fox, Elizabeth] NCI, Pediat Oncol Branch, Ctr Canc Res, Bethesda, MD 20892 USA. RP Chuk, MK (reprint author), NCI, Pediat Oncol Branch, Ctr Canc Res, 10 Ctr Dr,Bldg 10 CRC,Room 1W-5750, Bethesda, MD 20892 USA. EM chukme@mail.nih.gov FU NIH; National Cancer Institute FX This work was supported by the Intramural Research Program of the NIH, National Cancer Institute, Center for Cancer Research. The views expressed do not necessarily represent views of the National Institutes of Health or the U. S. government. NR 62 TC 8 Z9 8 U1 0 U2 2 PU ALPHAMED PRESS PI DURHAM PA 318 BLACKWELL ST, STE 260, DURHAM, NC 27701-2884 USA SN 1083-7159 EI 1549-490X J9 ONCOLOGIST JI Oncologist PY 2009 VL 14 IS 8 BP 794 EP 799 DI 10.1634/theoncologist.2009-0104 PG 6 WC Oncology SC Oncology GA 489HD UT WOS:000269409900004 PM 19684073 ER PT J AU Kim, A Balis, FM Widemann, BC AF Kim, AeRang Balis, Frank M. Widemann, Brigitte C. TI Sorafenib and Sunitinib SO ONCOLOGIST LA English DT Review DE Sorafenib; Sunitinib; Drug profile ID REFRACTORY SOLID TUMORS; ADVANCED HEPATOCELLULAR-CARCINOMA; TYROSINE KINASE INHIBITOR; RENAL-CELL CARCINOMA; PHASE-I; ANTITUMOR-ACTIVITY; CANCER; PHARMACOKINETICS; BAY-43-9006; COMBINATION C1 [Kim, AeRang; Balis, Frank M.; Widemann, Brigitte C.] NCI, Pediat Oncol Branch, Ctr Canc Res, Bethesda, MD 20892 USA. RP Kim, A (reprint author), NCI, Pediat Oncol Branch, Ctr Canc Res, 10 Ctr Dr,Bldg 10 CRC,Room 1-3872, Bethesda, MD 20892 USA. EM kimaer@mail.nih.gov FU NIH; National Cancer Institute FX This was supported by the Intramural Research Program of the NIH, National Cancer Institute, Center for Cancer Research. The views expressed do not necessarily represent the views of the National Institutes of Health or the U. S. government. NR 26 TC 25 Z9 28 U1 0 U2 3 PU ALPHAMED PRESS PI DURHAM PA 318 BLACKWELL ST, STE 260, DURHAM, NC 27701-2884 USA SN 1083-7159 J9 ONCOLOGIST JI Oncologist PY 2009 VL 14 IS 8 BP 800 EP 805 DI 10.1634/theoncologist.2009-0088 PG 6 WC Oncology SC Oncology GA 489HD UT WOS:000269409900005 PM 19648603 ER PT J AU Merchant, MS Mackall, CL AF Merchant, Melinda S. Mackall, Crystal L. TI Current Approach to Pediatric Soft Tissue Sarcomas SO ONCOLOGIST LA English DT Review DE Sarcoma; Soft tissue; Pediatric malignancy; Chemotherapy; Ewing's sarcoma; Synovial sarcoma ID ROUND-CELL TUMOR; CHILDRENS ONCOLOGY GROUP; NERVE SHEATH TUMORS; INTERMEDIATE RISK RHABDOMYOSARCOMA; MESENCHYMAL PROGENITOR CELLS; EARLY LYMPHOCYTE RECOVERY; ITALIAN-COOPERATIVE-GROUP; TOTAL-BODY IRRADIATION; HUMAN SYNOVIAL SARCOMA; END RESULTS PROGRAM AB The development of a new soft tissue lesion in an otherwise healthy child, adolescent, or young adult can present many challenges for pediatric or medical oncology teams. Although uncommon, the diagnosis of a soft tissue malignancy should always be considered in the differential diagnosis of persistent pain, even if no mass is palpable. The definitive diagnosis and treatment of a soft tissue mass is aided by timely scans, appropriate biopsy for anatomic and molecular pathology, and a treatment approach guided by the specific diagnosis. Because pediatric soft tissue sarcomas are rare, cooperative groups play a crucial role in defining the standard of care through retrospective series and well-designed prospective clinical trials. Enrollment of newly diagnosed patients in clinical studies should be encouraged in order to continue to improve outcomes and understanding of these rare tumors. This review focuses on the current recommendations for management of sarcomas that typically occur in the soft tissues of pediatric and young adult patients. The Oncologist 2009;14:1139-1153 C1 [Merchant, Melinda S.; Mackall, Crystal L.] NCI, Pediat Oncol Branch, NIH, Bethesda, MD 20892 USA. RP Merchant, MS (reprint author), NCI, Pediat Oncol Branch, NIH, 10 Ctr Dr,Bldg 10,Room 1W-3940, Bethesda, MD 20892 USA. EM merchanm@mail.nih.gov NR 117 TC 4 Z9 4 U1 1 U2 4 PU ALPHAMED PRESS PI DURHAM PA 318 BLACKWELL ST, STE 260, DURHAM, NC 27701-2884 USA SN 1083-7159 EI 1549-490X J9 ONCOLOGIST JI Oncologist PY 2009 VL 14 IS 11 BP 1139 EP 1153 DI 10.1634/theoncologist.2009-0160 PG 15 WC Oncology SC Oncology GA 524TS UT WOS:000272166800010 PM 19897537 ER PT J AU Muehlbauer, P AF Muehlbauer, Paula TI Look Beyond Breast Cancer SO ONCOLOGY NURSING FORUM LA English DT Letter C1 NIH, Bethesda, MD 20892 USA. RP Muehlbauer, P (reprint author), NIH, Bldg 10, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ONCOLOGY NURSING SOC PI PITTSBURGH PA 125 ENTERPRISE DR, PITTSBURGH, PA 15275 USA SN 0190-535X J9 ONCOL NURS FORUM JI Oncol. Nurs. Forum PD JAN PY 2009 VL 36 IS 1 BP 10 EP 10 PG 1 WC Oncology; Nursing SC Oncology; Nursing GA 396VV UT WOS:000262620200002 ER PT J AU Freeman, AF Domingo, DL Holland, SM AF Freeman, A. F. Domingo, D. L. Holland, S. M. TI Hyper IgE (Job's) syndrome: a primary immune deficiency with oral manifestations SO ORAL DISEASES LA English DT Review DE hyper IgE syndrome; Job's syndrome; immunodeficiency; primary teeth retention ID HYPERIMMUNOGLOBULIN-E SYNDROME; RECURRENT-INFECTION SYNDROME; COLD STAPHYLOCOCCAL ABSCESSES; INTERFERON-GAMMA; PATIENT; TRANSPLANTATION; CRYPTOCOCCOSIS; CYTOKINE; LYMPHOMA; PATHWAY AB Autosomal dominant hyper IgE (HIES or Job's) syndrome is a rare primary immune deficiency characterized by eczema, recurrent skin and lung infections, extremely elevated serum IgE, and a variety of connective tissue and skeletal abnormalities. Individuals with HIES share a characteristic facial appearance and many oral manifestations including retained primary dentition, a high arched palate, variations of the oral mucosa and gingiva, and recurrent oral candidiasis. Mutations in STAT3 account for the majority, if not all, of the cases of autosomal dominant HIES, but the pathogenesis of the many varied features remains poorly understood. In this review, we discuss the clinical phenotype of HIES including immunologic and non-immunologic features, the genetics of HIES, and treatment. C1 [Freeman, A. F.; Holland, S. M.] NIAID, Lab Clin Infect Dis, NIH, Bethesda, MD 20892 USA. [Freeman, A. F.] NCI, SAIC Frederick Inc, Frederick, MD 21701 USA. [Domingo, D. L.] Natl Inst Dent & Craniofacial Res, NIH, Bethesda, MD USA. RP Freeman, AF (reprint author), Bldg 10,CRC B3-4141,MSC 1684, Bethesda, MD 20892 USA. EM smh@nih.gov FU National Institute of Allergy and Infectious Diseases; National Cancer Institute; National Institutes of Health [N01-CO-12400] 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 N01-CO-12400. The content of this publication does not necessarily reflect the views or policies of the Department of Health and Human Services, nor does mention of trade names, commercial products, or organizations imply endorsement by the U. S. Government. NR 39 TC 12 Z9 16 U1 0 U2 1 PU WILEY-BLACKWELL PUBLISHING, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1354-523X J9 ORAL DIS JI Oral Dis. PD JAN PY 2009 VL 15 IS 1 BP 2 EP 7 DI 10.1111/j.1601-0825.2008.01463.x PG 6 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA 382OY UT WOS:000261616500002 PM 19036057 ER PT J AU Hanna, E Quick, J Libutti, SK AF Hanna, E. Quick, J. Libutti, S. K. TI The tumour microenvironment: a novel target for cancer therapy SO ORAL DISEASES LA English DT Review DE tumour microenvironment; combination therapy; endothelial cells; leucocytes; fibroblasts; extracellular matrix ID NECROSIS-FACTOR-ALPHA; ENDOTHELIAL GROWTH-FACTOR; ACTIVATING POLYPEPTIDE-II; ADVANCED HEPATOCELLULAR-CARCINOMA; SUBCUTANEOUS INTERFERON-ALPHA; EXPERIMENTAL SOLID TUMORS; ADOPTIVE CELL TRANSFER; HUMAN COLON-CANCER; CD8(+) T-CELLS; IN-VIVO AB Cancer therapy is in the midst of a major paradigm shift. Traditionally, cancer treatments have focused on tumour cells. However, studies over the past few decades have demonstrated that cancer is a vastly complex entity with multiple components affecting a tumour's growth, invasion and metastasis. These components, collectively termed the 'tumour microenvironment', include endothelial cells, pericytes, fibroblasts, inflammatory cells, leucocytes and elements of the extracellular matrix (ECM). Biological agents that target components of the tumour microenvironment may provide an interesting alternative to traditional tumour cell-directed therapy. Because of the complexity of the tumour milieu, the most beneficial therapy will likely involve the combination of one or more agents directed at this new target. This review highlights recent preclinical and clinical studies involving agents that target tumour vasculature, leucocytes, pericytes, cancer-associated fibroblasts and ECM components. We pay particular attention to combination therapies targeting multiple components of the tumour microenvironment, and aim to demonstrate that this strategy holds promise for the future of cancer treatment. C1 [Hanna, E.; Quick, J.; Libutti, S. K.] NCI, Tumour Angiogenesis Sect, Surg Branch, Ctr Canc Res,NIH, Bethesda, MD 20892 USA. [Quick, J.] NIH, Howard Hughes Med Inst, Res Scholars Program, Bethesda, MD 20892 USA. RP Libutti, SK (reprint author), NCI, Tumour Angiogenesis Sect, Surg Branch, Ctr Canc Res,NIH, Room 4W 5940,Bldg 10,10 Ctr Dr, Bethesda, MD 20892 USA. EM libuttis@mail.nih.gov NR 127 TC 43 Z9 48 U1 5 U2 27 PU WILEY-BLACKWELL PUBLISHING, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1354-523X J9 ORAL DIS JI Oral Dis. PD JAN PY 2009 VL 15 IS 1 BP 8 EP 17 DI 10.1111/j.1601-0825.2008.01471.x PG 10 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA 382OY UT WOS:000261616500003 PM 18992016 ER PT J AU Sugito, T Mineshiba, F Zheng, C Cotrim, AP Goldsmith, CM Baum, BJ AF Sugito, T. Mineshiba, F. Zheng, C. Cotrim, A. P. Goldsmith, C. M. Baum, B. J. TI Transient TWEAK overexpression leads to a general salivary epithelial cell proliferation SO ORAL DISEASES LA English DT Article DE TWEAK; gene transfer; adenoviral vector; cell division; progenitor cell ID RAT SUBMANDIBULAR-GLAND; PROGENITOR CELLS; MULTIFUNCTIONAL CYTOKINE; RECEPTOR; SECRETION; APOPTOSIS; PATHWAY; TARGET; MODEL; DUCT AB Tumor necrosis factor-like weak inducer of apoptosis (TWEAK) is a multifunctional cytokine that has pro-apoptotic, pro-angiogenic and pro-inflammatory effects. In liver, TWEAK leads to proliferation of progenitor oval cells, but not of mature hepatocytes. This study evaluated the hypothesis that TWEAK overexpression in salivary glands would lead to the proliferation of a salivary progenitor cell. A recombinant, serotype 5 adenoviral vector encoding human TWEAK, AdhTWEAK, was constructed, initially tested in vitro, and then administered to male Balb/c mice via cannulation of Wharton's duct. TWEAK expression in vivo was monitored as protein secreted into saliva and serum by enzyme-linked immunosorbent assays. Salivary cell proliferation was monitored by proliferating cell nuclear antigen staining and apoptosis was monitored using TUNEL staining. AdhTWEAK administration led to a dose-dependent, transient TWEAK protein expression, detected primarily in saliva. Salivary epithelial cell proliferation was generalized, peaking on similar to days 2 and 3. TWEAK expression had no detectable effect on apoptosis of salivary epithelial cells. Transient overexpression of TWEAK in murine salivary glands leads to a general proliferation of epithelial cells vs a selective stimulation of a salivary progenitor cell. C1 [Sugito, T.; Mineshiba, F.; Zheng, C.; Cotrim, A. P.; Goldsmith, C. M.; 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 35 TC 6 Z9 7 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 2009 VL 15 IS 1 BP 76 EP 81 DI 10.1111/j.1601-0825.2008.01474.x PG 6 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA 382OY UT WOS:000261616500011 PM 18992019 ER PT J AU Simpson, DS Lovell, KM Lozama, A Han, N Day, VW Dersch, CM Rothman, RB Prisinzano, TE AF Simpson, Denise S. Lovell, Kimberly M. Lozama, Anthony Han, Nina Day, Victor W. Dersch, Christina M. Rothman, Richard B. Prisinzano, Thomas E. TI Synthetic studies of neoclerodane diterpenes from Salvia divinorum: role of the furan in affinity for opioid receptors SO ORGANIC & BIOMOLECULAR CHEMISTRY LA English DT Article ID PLANT-DERIVED HALLUCINOGEN; AGONIST SALVINORIN-A; TEUCRIN-A; ENANTIOSELECTIVE SYNTHESIS; RICCIOCARPIN-B; RHESUS-MONKEYS; IN-VIVO; RATS; IDENTIFICATION; MICE AB Further synthetic modi. cation of the furan ring of salvinorin A (1), the major active component of Salvia divinorum, has resulted in novel neoclerodane diterpenes with opioid receptor affinity and activity. A computational study has predicted 1 to be a reproductive toxicant in mammals and is suggestive that use of 1 may be associated with adverse effects. We report in this study that piperidine 21 and thiomorpholine 23 have been identified as selective partial agonists at kappa opioid receptors. This indicates that additional structural modi. cations of 1 may provide ligands with good selectivity for opioid receptors but with reduced potential for toxicity. C1 [Simpson, Denise S.; Lovell, Kimberly M.; Lozama, Anthony; Prisinzano, Thomas E.] Univ Kansas, Dept Med Chem, Lawrence, KS 66045 USA. [Lozama, Anthony; Han, Nina] Univ Iowa, Div Med & Nat Prod Chem, Iowa City, IA USA. [Day, Victor W.] Univ Kansas, Dept Chem, Lawrence, KS 66045 USA. [Dersch, Christina M.; Rothman, Richard B.] NIDA, Clin Psychopharmacol Sect, IRP, NIH,DHHS, Baltimore, MD USA. RP Prisinzano, TE (reprint author), Univ Kansas, Dept Med Chem, Lawrence, KS 66045 USA. EM prisinza@ku.edu RI Prisinzano, Thomas/B-7877-2010 FU NIH [SIG S10 RR019398]; National Institute on Drug Abuse (NIDA) [R01DA018151S1]; Intramural Research Program; National Institute on Drug Abuse; DHHS FX We wish to thank (Dr ToddWilliams, Mr Robert Drake, Mr Larry Sieb) of the KU mass spectrometry laboratory for their efforts in acquiring the ESI spectra. LCT Premier was purchased with support from NIH SIG S10 RR019398. This work was supported by Grant Numbers R01DA018151 and R01DA018151S1 (to TEP) from the National Institute on Drug Abuse (NIDA). Portions of this work were also supported by the Intramural Research Program, National Institute on Drug Abuse, National Institutes of Health, DHHS. In silico computational toxicology testing was completed with the support of NIDA's Addiction Treatment Discovery Program through the use of Interagency Agreement Y1DA6003. The content is the sole responsibility of the authors and does not necessarily represent the of. cial views of the National Institute on Drug Abuse or the National Institutes of Health. NR 55 TC 11 Z9 12 U1 1 U2 6 PU ROYAL SOC CHEMISTRY PI CAMBRIDGE PA THOMAS GRAHAM HOUSE, SCIENCE PARK, MILTON RD, CAMBRIDGE CB4 0WF, CAMBS, ENGLAND SN 1477-0520 EI 1477-0539 J9 ORG BIOMOL CHEM JI Org. Biomol. Chem. PY 2009 VL 7 IS 18 BP 3748 EP 3756 DI 10.1039/b905148a PG 9 WC Chemistry, Organic SC Chemistry GA 488CU UT WOS:000269327500018 PM 19707679 ER PT J AU Ratnayake, R Covell, D Ransom, TT Gustafson, KR Beutler, JA AF Ratnayake, Ranjala Covell, David Ransom, Tanya T. Gustafson, Kirk R. Beutler, John A. TI Englerin A, a Selective Inhibitor of Renal Cancer Cell Growth, from Phyllanthus engleri SO ORGANIC LETTERS LA English DT Article ID EUPHORBIACEAE; BIOASSAYS; USAGE; COMPILATION; TOXICITY; ACID AB An extract from Phyllanthus engleri was identified in a bioinformatic analysis of NCI 60-cell natural product extract screening data that selectively Inhibited the growth of renal cancer cell lines. Bioassay-guided fractionation yielded two new gualane sesquiterpenes, englerins A (1) and B (2). Englerin A showed 1000-fold selectivity against six of eight renal cancer cell lines with GI(50) values ranging from 1-87 nM. The structures of I and 2 and their relative stereochemistry were established by spectroscopic methods, C1 [Ratnayake, Ranjala; Ransom, Tanya T.; Gustafson, Kirk R.; Beutler, John A.] Ctr Canc Res, Mol Targets Dev Program, Frederick, MD 21702 USA. [Covell, David] NCI, Screening Technol Branch, Dev Therapeut Program, Frederick, MD 21702 USA. RP Beutler, JA (reprint author), Ctr Canc Res, Mol Targets Dev Program, Frederick, MD 21702 USA. EM beutlerj@mail.nih.gov RI Beutler, John/B-1141-2009 OI Beutler, John/0000-0002-4646-1924 FU NIH; National Cancer Institute; Center for Cancer Research; Developmental Therapeutics Program in the Division of Cancer Treatment; Diagnosis of the National Cancer Institute FX We thank the Missouri Botanical Garden collectors (Roy Gereau, James Lovett, C. O. Kyalawa, and Z. H. Mbwambo) for the plant collection, Thomas McCloud (Natural Products Support Group, NCI-Frederick) for plant extraction, Melinda Hollingshead (Biological Testing Branch, DTP) for mouse toxicity studies, and Sergey Tarasov and Marzena. Dyba (Biophysics Resource Core, Structural Biophysics Laboratory, CCR) for assistance with high-resolution mass spectrometry. This research was supported jointly by the Intramural Research Program of the NIH, National Cancer Institute, Center for Cancer Research, and by the Developmental Therapeutics Program in the Division of Cancer Treatment and Diagnosis of the National Cancer Institute. NR 19 TC 80 Z9 80 U1 5 U2 35 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 1523-7060 J9 ORG LETT JI Org. Lett. PD JAN 1 PY 2009 VL 11 IS 1 BP 57 EP 60 DI 10.1021/ol802339w PG 4 WC Chemistry, Organic SC Chemistry GA 388KM UT WOS:000262018700015 PM 19061394 ER PT J AU Saavedra, JE Davies, KM Barchi, JJ Keefer, LK AF Saavedra, Joseph E. Davies, Keith M. Barchi, Joseph J., Jr. Keefer, Larry K. TI Unexpected Incorporation of Bromine at a Non-anomeric Position during the Synthesis of an O-2-Glycosylated Diazeniumdiolate SO ORGANIC PREPARATIONS AND PROCEDURES INTERNATIONAL LA English DT Article ID OXIDE C1 [Saavedra, Joseph E.] NCI, Basic Res Program, SAIC Frederick, Frederick, MD 21702 USA. [Davies, Keith M.] George Mason Univ, Dept Chem, Fairfax, VA 22030 USA. [Barchi, Joseph J., Jr.] NCI, Med Chem Lab, Frederick, MD 21702 USA. [Keefer, Larry K.] NCI, Chem Sect, Comparat Carcinogenesis Lab, Frederick, MD 21702 USA. RP Saavedra, JE (reprint author), NCI, Basic Res Program, SAIC Frederick, Frederick, MD 21702 USA. EM saavj@mail.ncifcrf.gov RI Barchi Jr., Joseph/N-3784-2014; Keefer, Larry/N-3247-2014 OI Keefer, Larry/0000-0001-7489-9555 FU National Cancer Institute, National Institutes of Health [NO1-CO-2008-00001] FX This project has been funded in part with federal funds from the National Cancer Institute, National Institutes of Health, under contract NO1-CO-2008-00001, and in part by the Intramural Research Program of the NIH, National Cancer Institute, Center for Cancer Research. The content of this article does not necessarily reflect the views or policies of the Department of Health and Human Services, nor does mention of tradenames, commercial products, or organizations imply endorsement by the U. S. Government. NR 4 TC 0 Z9 0 U1 0 U2 1 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 325 CHESTNUT ST, SUITE 800, PHILADELPHIA, PA 19106 USA SN 0030-4948 J9 ORG PREP PROCED INT JI Org. Prep. Proced. Int. PY 2009 VL 41 IS 2 BP 143 EP 147 DI 10.1080/00304940902801968 PG 5 WC Chemistry, Organic SC Chemistry GA 587ML UT WOS:000276996500002 ER PT J AU Ling, SM Patel, DD Garnero, P Zhan, M Vaduganathan, M Muller, D Taub, D Bathon, JM Hochberg, M Abernethy, DR Metter, EJ Ferrucci, L AF Ling, S. M. Patel, D. D. Garnero, P. Zhan, M. Vaduganathan, M. Muller, D. Taub, D. Bathon, J. M. Hochberg, M. Abernethy, D. R. Metter, E. J. Ferrucci, L. TI Serum protein signatures detect early radiographic osteoarthritis SO OSTEOARTHRITIS AND CARTILAGE LA English DT Article DE Osteoarthritis; Proteins; Biomarkers; Inflammation; Aging ID RHEUMATOID-ARTHRITIS; CARTILAGE; KNEE; EXPRESSION; MICROARRAYS; AGGRECAN; HIP AB Objective: To test the hypothesis that early knee and hand osteoarthritis (OA) development is characterized by detectable changes in serum proteins relevant to inflammation, cell growth, activation, and metabolism several years before OA becomes radiographically evident. Methods: Using microarray platforms that simultaneously test 169 proteins relevant to inflammation, cell growth, activation and metabolism, we conducted a case-control study nested within the Baltimore Longitudinal Study of Aging (BLSA). Subjects included 22 incident cases of OA and 66 age-, sex- and body mass index (BMI)-matched controls. Serum samples tested were obtained at the time of radiographic classification as either case or control, and up to 10 years earlier at a time when all participants were free of radiographic OA. Proteins with mean signal intensities fourfold higher than background were compared between cases and controls using multivariate techniques. Results: Sixteen proteins were different between OA cases compared to controls. Four of these proteins [matrix metalloproteinase (MMP)-7, interleukin (IL)-15, plasminogen activator inhibitor (PAI)-1 and soluble vascular adhesion protein (sVAP)-1] were already different in samples obtained 10 years before radiographic classification and remained different at the time of diagnosis. Six additional proteins were only associated with subsequent OA development and not with established OA. Conclusions: Changes in serum proteins implicated in matrix degradation, cell activation, inflammation and bone collagen degradation products accompany early OA development and can precede radiographic detection by several years. Published by Elsevier Ltd on behalf of Ostecarthritis Research Society International. C1 [Ling, S. M.; Zhan, M.; Vaduganathan, M.; Muller, D.; Taub, D.; Abernethy, D. R.; Metter, E. J.; Ferrucci, L.] NIA, Intramural Res Program, NIH, Baltimore, MD 21224 USA. [Patel, D. D.] Univ N Carolina, Thurston Arthrit Res Ctr, Div Rheumatol Allergy & Immunol, Chapel Hill, NC USA. [Garnero, P.] INSERM, Res Unit & Synarc 664, F-69008 Lyon, France. [Bathon, J. M.] Johns Hopkins Med Inst, Div Rheumatol, Baltimore, MD 21205 USA. [Hochberg, M.] Univ Maryland, Sch Med, Div Clin Immunol & Rheumatol, Baltimore, MD 21201 USA. RP Ling, SM (reprint author), Harbor Hosp, Clin Res Branch, NM 533 3001 S Hanover St, Baltimore, MD 21225 USA. EM lingsh@grc.nia.nih.gov FU Intramural Research Program of the National Institutes of Health; National Institute on Aging. Dhavalkumar Patel FX This work was supported by the Intramural Research Program of the National Institutes of Health, National Institute on Aging. Dhavalkumar Patel also has received support from Molecular Staging, Inc up until 2004. This company no longer exists. Patrick Gamero is an employee of Synarc SAS. Synarc assays were performed in a blinded fashion, through a material transfer agreement. NR 24 TC 30 Z9 31 U1 2 U2 14 PU W B SAUNDERS CO LTD PI LONDON PA 32 JAMESTOWN RD, LONDON NW1 7BY, ENGLAND SN 1063-4584 J9 OSTEOARTHR CARTILAGE JI Osteoarthritis Cartilage PD JAN PY 2009 VL 17 IS 1 BP 43 EP 48 DI 10.1016/j.joca.2008.05.004 PG 6 WC Orthopedics; Rheumatology SC Orthopedics; Rheumatology GA 400SS UT WOS:000262889500007 PM 18571442 ER PT J AU Xie, H Gu, XX AF Xie, H. Gu, X. X. BE Park, K Choung, YH Park, HJ Chun, YM TI Regulatory mechanisms of Moraxella catarrhalis lipooligosaccharide induced ICAM-1 expression and potential impact on otitis media with effusion (OME) SO OTITIS MEDIA 2009: 6TH EXTRAORDINARY INTERNATIONAL SYMPOSIUM ON RECENT ADVANCES IN OTITIS MEDIA LA English DT Proceedings Paper CT 6th Extraordinary International Symposium on Recent Advances in Otitis Media Research CY MAY 06-10, 2009 CL Seoul, SOUTH KOREA SP Ajou Univ, ENT Alumni, Yonsei Univ, Chosun Univ ID CARTILAGE PALISADE TYMPANOPLASTY; TENSA RETRACTION CHOLESTEATOMA; FASCIA; SINUS AB Previously we have reported that Moraxella catarrhalis lipooligosaccharide (LOS) differentially enhances intercellular adhesion molecule 1 (ICAM-1) expression on human monocytes. Further investigations have suggested that this M. catarrhalis LOS induced up-regulation of ICAM-1 required TLR4, surface CD14 and serum lipopolysaccharide binding protein (LBP), and was partially mediated through a TNF-alpha dependent autocrine mechanism. NF-kappa B p65 and JNK1 also participate in the regulation of LOS stimulated ICAM-1 expression. Moreover, the LOS activated human monocytes could stimulate adjacent naive monocytes to produce TNF-alpha, which partially depended on surface ICAM-1 and IL-8RA expression. Our results suggest that M. catarrhalis LOS could induce excessive middle ear inflammation by selectively up-regulating surface ICAM-1 expression of host cells during OME development. C1 [Xie, H.; Gu, X. X.] Natl Inst Deafness & Other Commun Disorders, Vaccine Res Sect, NIH, Rockville, MD 20850 USA. RP Xie, H (reprint author), Natl Inst Deafness & Other Commun Disorders, Vaccine Res Sect, NIH, Rockville, MD 20850 USA. NR 6 TC 0 Z9 0 U1 2 U2 2 PU MEDIMOND S R L PI 40128 BOLOGNA PA VIA MASERATI 5, 40128 BOLOGNA, 00000, ITALY BN 978-88-7587-542-8 PY 2009 BP 45 EP 52 PG 8 WC Otorhinolaryngology SC Otorhinolaryngology GA BQS43 UT WOS:000281730600008 ER PT J AU Peng, D Gao, S Zhang, W Muszynski, A Carlson, RW Gu, XX AF Peng, D. Gao, S. Zhang, W. Muszynski, A. Carlson, R. W. Gu, X. X. BE Park, K Choung, YH Park, HJ Chun, YM TI Virulence genes in Moraxella catarrhalis lipopolysaccharide biosynthesis pathway SO OTITIS MEDIA 2009: 6TH EXTRAORDINARY INTERNATIONAL SYMPOSIUM ON RECENT ADVANCES IN OTITIS MEDIA LA English DT Proceedings Paper CT 6th Extraordinary International Symposium on Recent Advances in Otitis Media Research CY MAY 06-10, 2009 CL Seoul, SOUTH KOREA SP Ajou Univ, ENT Alumni, Yonsei Univ, Chosun Univ ID IDENTIFICATION AB We have previously found several potential virulence genes involved in Moraxella catarrhalis lipooligosaccharide (LOS) biosynthesis pathway. The genes include kdtA, lgt3, lpxA and lpxL/X. Using either a random transposon mutagenesis or bioinformatics approach, each corresponding knockout mutant has been generated and its truncated LOS structure confirmed by MALDI-TOF MS, glycosyl composition, linkage, and NMR analyses of de-O-acylated LOS or oligosaccharide (OS) from the mutant. Phenotypic studies revealed that the mutants showed different patterns in their growth rate, toxicity and susceptibility to hydrophobic reagents. However, most mutants with truncated LOS structure in OS and/or lipid A presented reduced resistance to the bactericidal activity of normal human serum, reduced adherence to human epithelial cells, and increased bacterial clearance in animals. Our data suggest that a complete OS moiety of the LOS is important for serum resistance and adherence to epithelial cells, and both the OS and lipid A moieties contribute to the LOS virulence. C1 [Peng, D.; Gao, S.; Zhang, W.; Gu, X. X.] Natl Inst Deafness & Other Commun Disorders, Vaccine Res Sect, NIH, Rockville, MD 20850 USA. RP Peng, D (reprint author), Natl Inst Deafness & Other Commun Disorders, Vaccine Res Sect, NIH, Rockville, MD 20850 USA. NR 9 TC 0 Z9 0 U1 0 U2 0 PU MEDIMOND S R L PI 40128 BOLOGNA PA VIA MASERATI 5, 40128 BOLOGNA, 00000, ITALY BN 978-88-7587-542-8 PY 2009 BP 107 EP 110 PG 4 WC Otorhinolaryngology SC Otorhinolaryngology GA BQS43 UT WOS:000281730600018 ER PT S AU Farley, J Birrer, MJ AF Farley, John Birrer, Michael J. BE Stack, MS Fishman, DA TI Novel Therapeutic Targets SO OVARIAN CANCER, SECOND EDITION SE Cancer Treatment and Research LA English DT Article; Book Chapter ID EPITHELIAL OVARIAN-CANCER; PHASE-II TRIAL; GYNECOLOGIC-ONCOLOGY-GROUP; GROWTH-FACTOR RECEPTORS; MATRIX-METALLOPROTEINASE INHIBITORS; PACLITAXEL-MEDIATED CYTOTOXICITY; METASTATIC COLORECTAL-CANCER; PRIMARY PERITONEAL CARCINOMA; DEPENDENT KINASE INHIBITOR; MONOCLONAL-ANTIBODY C225 C1 [Birrer, Michael J.] Harvard Univ, Sch Med, Boston, MA 02114 USA. [Birrer, Michael J.] Harvard Canc Ctr, Gynecol Canc Res Program, Boston, MA 02114 USA. [Birrer, Michael J.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Farley, John] Uniformed Serv Univ Hlth Sci, Dept Obstet & Gynecol, Bethesda, MD 20814 USA. [Farley, John] NCI, Christina Annunziata Ctr Canc Res, Med Oncol Branch, Bethesda, MD 20892 USA. RP Birrer, MJ (reprint author), Harvard Univ, Sch Med, 55 Fruit St, Boston, MA 02114 USA. EM mbirrer@partners.org NR 119 TC 2 Z9 2 U1 0 U2 0 PU SPRINGER PI DORDRECHT PA PO BOX 17, 3300 AA DORDRECHT, NETHERLANDS SN 0927-3042 BN 978-0-387-98093-5 J9 CANCER TREAT RES JI Canc. Treat. Res. PY 2009 VL 149 BP 63 EP 84 DI 10.1007/978-0-387-98094-2_3 PG 22 WC Oncology SC Oncology GA BMT32 UT WOS:000273526200003 PM 19763431 ER PT S AU ElMasri, WM Casagrande, G Hoskins, E Kimm, D Kohn, EC AF ElMasri, Wafic M. Casagrande, Giovanna Hoskins, Ebony Kimm, Daniel Kohn, Elise C. BE Stack, MS Fishman, DA TI Cell Adhesion in Ovarian Cancer SO OVARIAN CANCER, SECOND EDITION SE Cancer Treatment and Research LA English DT Article; Book Chapter ID ENDOTHELIAL GROWTH-FACTOR; E-CADHERIN EXPRESSION; EPITHELIAL-MESENCHYMAL TRANSITIONS; RECEPTOR TYROSINE KINASE; MOLECULE E-CADHERIN; SOLUBLE P-SELECTIN; SIALYL-LEWIS-X; BETA-CATENIN; TUMOR-PROGRESSION; ALPHA-CATENIN C1 [ElMasri, Wafic M.; Casagrande, Giovanna; Hoskins, Ebony; Kimm, Daniel; Kohn, Elise C.] Natl Canc Inst, Med Oncol Branch, Ctr Canc Res, Bethesda, MD 20892 USA. RP Kohn, EC (reprint author), Natl Canc Inst, Med Oncol Branch, Ctr Canc Res, Bethesda, MD 20892 USA. EM kohne@mail.nih.gov NR 164 TC 5 Z9 5 U1 0 U2 1 PU SPRINGER PI DORDRECHT PA PO BOX 17, 3300 AA DORDRECHT, NETHERLANDS SN 0927-3042 BN 978-0-387-98093-5 J9 CANCER TREAT RES JI Canc. Treat. Res. PY 2009 VL 149 BP 297 EP 318 DI 10.1007/978-0-387-98094-2_14 PG 22 WC Oncology SC Oncology GA BMT32 UT WOS:000273526200014 PM 19763442 ER PT B AU Okun, E Mattson, MP AF Okun, Eitan Mattson, Mark P. BE Veasey, SC TI Neuronal Vulnerability to Oxidative Damage in Aging SO OXIDATIVE NEURAL INJURY SE Contemporary Clinical Neuroscience LA English DT Article; Book Chapter DE ALS; Alzheimer's disease; Free radicals; Hormesis; Huntington's disease; Hydroxynonenal; Lipid peroxidation; Parkinson's disease; Peroxynitrite ID AMYOTROPHIC-LATERAL-SCLEROSIS; ALZHEIMERS-DISEASE; LIPID-PEROXIDATION; NEURODEGENERATIVE DISORDERS; FREE-RADICALS; MITOCHONDRIAL DYSFUNCTION; CALORIC RESTRICTION; PARKINSONS-DISEASE; GENE-EXPRESSION; DNA-DAMAGE AB The aging process in the brain is as robust as it is in other body organs and manifests as decrements in cognition, sensory and motor abilities, and autonomic control of various organ systems. This is due to the fact that, with advancing age, brain cells are exposed to increasing levels of oxidative stress, disturbed energy homeostasis, and accumulation of damage to protein, lipids, and nucleic acids. While these changes occur during normal aging, they are exacerbated in neurons that are susceptible to neurodegenerative disorders. The final outcome of the balance between a person's own genetic background and the environmental changes that affect him or her determines if and when a neurodegenerative disorder will occur. Oxidative molecular alterations that occur during normal aging and that are amplified in the neurons that are affected in neurodegenerative disorders include protein nitrosylation, oxidation of amino acids and DNA bases, lipid peroxidation, and increased amounts of neurotoxic amino acid derivates such as homocysteine. Oxidative damage may render neurons vulnerable to metabolic stress, excitotoxicity, and apoptosis in Alzheimer's disease (AD), Parkinson's disease (PD), Huntington's disease (HD), and amyotrophic lateral sclerosis (ALS). Oxidative stress contributes to the abnormal protein aggregations specific to each disorder - amyloid beta-peptide (A beta) in AD, alpha-synuclein in PD, huntingtin in HD, and Cu/Zn-superoxide dismutase (Cu/Zn-SOD) in ALS. These protein inclusions may arise, in part, from impaired proteasome function and autophagy. Although the utility of antioxidant ingestion as a preventative strategy for age-related neurological disorders has not yet been demonstrated, age- and disease-related oxidative damage to neurons can be decreased by dietary energy restriction and exercise and accelerated by overeating and diabetes. C1 [Okun, Eitan; Mattson, Mark P.] NIA, Neurosci Lab, Intramural Res Program, Baltimore, MD 21224 USA. RP Mattson, MP (reprint author), NIA, Neurosci Lab, Intramural Res Program, Baltimore, MD 21224 USA. EM omalleyk@pcg.wustl.edu; mattsonm@grc.nia.nih.gov RI okun, eitan/K-1314-2016 OI okun, eitan/0000-0001-8474-1487 NR 72 TC 1 Z9 1 U1 1 U2 2 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DR, STE 208, TOTOWA, NJ 07512-1165 USA BN 978-1-60327-341-1 J9 CONTEMP CLIN NEUROSC PY 2009 BP 83 EP 95 DI 10.1007/978-1-60327-342-8_5 D2 10.1007/978-1-60327-342-8 PG 13 WC Clinical Neurology SC Neurosciences & Neurology GA BKK33 UT WOS:000268373600006 ER PT S AU Rifkind, JM Nagababu, E Cao, ZL Barbiro-Michaely, E Mayevsky, A AF Rifkind, Joseph M. Nagababu, Enika Cao, Zeling Barbiro-Michaely, Efrat Mayevsky, Avraham BE Liss, P Hansell, P Bruley, DF Harrison, DK TI NITRITE-INDUCED IMPROVED BLOOD CIRCULATION ASSOCIATED WITH AN INCREASE IN A POOL OF RBC-NO WITH NO BIOACTIVITY SO OXYGEN TRANSPORT TO TISSUE XXX SE Advances in Experimental Medicine and Biology LA English DT Article; Proceedings Paper CT 35th Annual Conference of the International-Society-on-Oxygen-Transport-to-Tissue CY 2007 CL Uppsala, SWEDEN SP Int Soc Oxygen Transport Tissue ID RED-CELL; REDUCTION; OXIDATION; OXIDE; HEMOGLOBIN AB The reduction of nitrite by RBCs producing NO can play a role in regulating vascular tone. This hypothesis was investigated in rats by measuring the effect of nitrite infusion on mean arterial blood pressure (MAP), cerebral blood flow (CBF) and cerebrovascular resistance (CVR) in conjunction with the accumulation of RBC-NO. The nitrite infusion reversed the increase in MAP and decrease in CBF produced by L-NAME inhibition of e-NOS. At the same time there was a dramatic increase in RBC-NO. Correlations of RBC-NO for individual rats support a role for the regulation or vascular tone by this pool of NO. Furthermore, data obtained prior to treatment with L-NAME or nitrite are consistent with a contribution of RBC reduced nitrite in regulating vascular tone even under normal conditions. The role of the RBC in delivering NO to the vasculature was explained by the accumulation of a pool of bioactive NO in the RBC when nitrite is reduced by deoxygenated hemoglobin chains. A comparison of R and T state hemoglobin demonstrated a potential mechanism for the release of this NO in the T-state present at reduced oxygen pressures when blood enters the microcirculation. Coupled with enhanced hemoglobin binding to the membrane under these conditions the NO can be released to the vasculature. C1 [Rifkind, Joseph M.; Nagababu, Enika; Cao, Zeling] NIA, Mol Dynam Sect, Baltimore, MD 21224 USA. [Barbiro-Michaely, Efrat; Mayevsky, Avraham] Bar Ilan Univ, Mina & Everard Goodman Fac Life Sci, IL-52100 Ramat Gan, Israel. RP Rifkind, JM (reprint author), NIA, Mol Dynam Sect, 5600 Nathan Shock Dr, Baltimore, MD 21224 USA. EM rifkindj@mail.nih.gov FU Intramural NIH HHS [Z01 AG000433-01] NR 14 TC 8 Z9 9 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013, UNITED STATES SN 0065-2598 BN 978-0-387-85997-2 J9 ADV EXP MED BIOL JI Adv.Exp.Med.Biol. PY 2009 VL 645 BP 27 EP 34 DI 10.1007/978-0-387-85998-9_5 PG 8 WC Medicine, Research & Experimental; Physiology SC Research & Experimental Medicine; Physiology GA BIT62 UT WOS:000262627100005 PM 19227446 ER PT J AU Klebanoff, MA AF Klebanoff, Mark A. TI The Collaborative Perinatal Project: a 50-year retrospective SO PAEDIATRIC AND PERINATAL EPIDEMIOLOGY LA English DT Article ID CEREBRAL-PALSY; UNITED-STATES; BILIRUBIN; MORTALITY; AGE C1 Eunice Kennedy Shriver NICHHD, Epidemiol Branch, NIH, Dept Hlth & Human Serv,NICHD, Bethesda, MD 20892 USA. RP Klebanoff, MA (reprint author), Eunice Kennedy Shriver NICHHD, Epidemiol Branch, NIH, Dept Hlth & Human Serv,NICHD, 6100 Bldg,Room 7 B05, Bethesda, MD 20892 USA. EM mk90h@nih.gov FU NIH; National Institute of Child Health and Human Development FX Dr Klebanoff is supported by the Intramural Research Program of the NIH, National Institute of Child Health and Human Development. NR 37 TC 21 Z9 21 U1 1 U2 1 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0269-5022 EI 1365-3016 J9 PAEDIATR PERINAT EP JI Paediatr. Perinat. Epidemiol. PD JAN PY 2009 VL 23 IS 1 BP 2 EP 8 DI 10.1111/j.1365-3016.2008.00984.x PG 7 WC Public, Environmental & Occupational Health; Obstetrics & Gynecology; Pediatrics SC Public, Environmental & Occupational Health; Obstetrics & Gynecology; Pediatrics GA 377TH UT WOS:000261273000002 PM 19228308 ER PT J AU Davila, JA Chiao, EY Hasche, JC Petersen, NJ McGlynn, KA Shaib, YH AF Davila, Jessica A. Chiao, Elizabeth Y. Hasche, Jennifer C. Petersen, Nancy J. McGlynn, Katherine A. Shaib, Yasser H. TI Utilization and Determinants of Adjuvant Therapy Among Older Patients Who Receive Curative Surgery for Pancreatic Cancer SO PANCREAS LA English DT Article DE pancreatic cancer; adjuvant therapy; SEER-Medicare ID LONG-TERM SURVIVAL; DUCTAL ADENOCARCINOMA; ELDERLY-PATIENTS; RESECTION; PANCREATICODUODENECTOMY; CHEMORADIOTHERAPY; CHEMOTHERAPY; CARCINOMA; REGION; TRIAL AB Objective: We conducted a population-based study to describe the utilization, determinants, and survival effects of adjuvant therapies after surgery among older patients with pancreatic cancer. Methods: Using Surveillance, Epidemiology, and End Results-Medicare data, we identified patients older than 65 years who received surgical resection for pancreatic cancer during 1992-2002. We constructed multiple logistic regression models to examine patient, clinical, and hospital factors associated with receiving adjuvant therapy. Cox proportional hazards models were used to examine the effect of therapy on survival. Results: Approximately 49% of patients received adjuvant therapy after surgery. Patient factors associated with increased receipt of adjuvant therapy included more recent diagnosis, younger age, stage II disease, higher income, and geographic location. Hospital factors associated with increased receipt of adjuvant therapy included cooperative group membership and larger size. Adjuvant treatments associated with a significant reduction in 2-year mortality (relative to surgery alone) were chemoradiation or radiation alone but not chemotherapy alone. Conclusions: Our findings suggest that adjuvant chemoradiation and, to a lesser degree, radiation only are associated with a reduction in the risk of mortality among older patients who undergo surgery for pancreatic cancer. However, receipt of adjuvant therapy varied by period and geography as well as by certain patient and hospital factors. C1 [Davila, Jessica A.; Chiao, Elizabeth Y.; Hasche, Jennifer C.; Petersen, Nancy J.; Shaib, Yasser H.] Baylor Coll Med, Sect Hlth Serv Res, Houston Vet Affairs Med Ctr, Houston, TX 77030 USA. [Chiao, Elizabeth Y.] Baylor Coll Med, Infect Dis Sect, Houston Vet Affairs Med Ctr, Houston, TX 77030 USA. [McGlynn, Katherine A.] NCI DHHS, Div Canc Epidemiol & Genet, Bethesda, MD USA. [Shaib, Yasser H.] Baylor Coll Med, Gastroenterol Sect, Houston Vet Affairs Med Ctr, Houston, TX 77030 USA. RP Davila, JA (reprint author), Baylor Coll Med, Sect Hlth Serv Res, Houston Vet Affairs Med Ctr, 2002 Holcombe Blvd 152, Houston, TX 77030 USA. EM jdavila@bcm.tmc.edu FU Dan L. Duncan Cancer Center, Baylor College of Medicine FX This study was supported by pilot funding from the Dan L. Duncan Cancer Center, Baylor College of Medicine. NR 18 TC 19 Z9 20 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0885-3177 J9 PANCREAS JI Pancreas PD JAN PY 2009 VL 38 IS 1 BP E18 EP E25 DI 10.1097/MPA.0b013e318187eb3f PG 8 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 392QP UT WOS:000262317600025 PM 18797424 ER PT J AU Kreps, G AF Kreps, Gary BE Socha, TJ Stamp, GH TI Commentary Communication and Family Health and Wellness Relationships SO PARENTS AND CHILDREN COMMUNICATING WITH SOCIETY: MANAGING RELATIONSHIPS OUTSIDE OF THE HOME SE Routledge Communications Series LA English DT Editorial Material; Book Chapter ID CARE; BEHAVIORS C1 [Kreps, Gary] George Mason Univ, Ctr Hlth & Risk Commun, Fairfax, VA 22030 USA. [Kreps, Gary] George Mason Univ, Dept Commun, Fairfax, VA 22030 USA. [Kreps, Gary] NCI, NIH, Bethesda, MD 20892 USA. RP Kreps, G (reprint author), George Mason Univ, Ctr Hlth & Risk Commun, Fairfax, VA 22030 USA. NR 17 TC 0 Z9 0 U1 0 U2 0 PU ROUTLEDGE PI LONDON PA 11 NEW FETTER LANE, LONDON EC4P 4EE, ENGLAND BN 978-0-203-93860-7 J9 ROUTL COMMUN SER PY 2009 BP 207 EP 212 PG 6 WC Communication; Family Studies SC Communication; Family Studies GA BNT23 UT WOS:000275479500013 ER PT S AU Kim, SY Helman, LJ AF Kim, Su Young Helman, Lee J. BE Jaffe, N Bruland, OS Bielack, SS TI Strategies to Explore New Approaches in the Investigation and Treatment of Osteosarcoma SO PEDIATRIC AND ADOLESCENT OSTEOSARCOMA SE Cancer Treatment and Research LA English DT Proceedings Paper CT Symposium on Pediatric and Adolescent Osteosarcoma CY MAR 06-08, 2008 CL Univ Texas, MD Anderson Canc Ctr, Houston, TX HO Univ Texas, MD Anderson Canc Ctr ID GROWTH-FACTOR-I; METASTATIC BEHAVIOR; OSTEOGENIC-SARCOMA; RETINOBLASTOMA GENE; PROGNOSTIC-FACTOR; EXPRESSION; CANCER; HETEROZYGOSITY; INVOLVEMENT; INHIBITION AB Studies in osteosarcoma over the past 40 years have led to a steady improvement in the overall outcome of patients with osteosarcoma. In the year 2008, we can expect greater than 60% overall survival for newly diagnosed non-metastatic appendicular osteosarcoma. However, to achieve this current outcome, many patients are treated with aggressive cytotoxic chemotherapy and ultimately are not cured, and some patients who would be curable even without this aggressive approach are likely treated and cured. And finally, patients presenting with metastatic disease and those whose tumors recur after standard approaches continue to do very poorly. We believe that in order to continue to make progress in the treatment of this disease, we must achieve two main objectives. Firstly, we must find biomarkers that prospectively and accurately identify newly diagnosed non-metastatic patients who will not be cured with current modalities. We hope that the achievement of this goal will allow for innovative clinical studies in this high-risk population while not jeopardizing those patients who currently are cured using the available treatment approaches, and ultimately accelerate progress toward caring more patients. Secondly, we must develop entirely new approaches to the treatment of metastatic and recurrent osteosarcoma. Our approach has been to develop models of highly aggressive and less aggressive osteosarcoma, and to use these models to identify genetic alterations and signaling pathways that distinguish the two phenotypic behaviors. We have identified plasma membrane-cytoskeletal linker protein, ezrin, as one pathway that identifies aggressive biological behavior in mouse and dog osteosarcoma. Using ezrin as the initial discriminator, we have high ezrin expression to activation of mTOR signaling, suggesting a possible novel target for therapy of aggressive osteosarcoma. We have also linked beta 4 integrin signaling to metastatic behavior that also appears to be linked to mTOR signaling. Most recently, we have identified a critical relationship between mTOR signaling and the IGF I signaling pathway that may help point the way to combination targeting therapy aimed at blocking both mTOR and ICF signaling in these tumors. Finally, we have proposed a novel clinical trial design to begin to test agents targeted at recurrent, metastatic disease, and this also will be discussed. C1 [Kim, Su Young; Helman, Lee J.] NCI, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. RP Helman, LJ (reprint author), NCI, Ctr Canc Res, NIH, 31 Ctr Dr,MSC 2440, Bethesda, MD 20892 USA. EM helmanl@mail.nih.gov NR 34 TC 19 Z9 21 U1 0 U2 0 PU SPRINGER PI DORDRECHT PA PO BOX 17, 3300 AA DORDRECHT, NETHERLANDS SN 0927-3042 BN 978-1-4419-0283-2 J9 CANCER TREAT RES JI Canc. Treat. Res. PY 2009 VL 152 BP 517 EP 528 DI 10.1007/978-1-4419-0284-9_31 PG 12 WC Oncology; Pediatrics SC Oncology; Pediatrics GA BMS92 UT WOS:000273510800031 PM 20213413 ER PT J AU Tran, SM Nobrega, RQ Kammerer, WA Quezado, Z AF Tran, Stephanie M. Nobrega, Raissa Q. Kammerer, William A. Quezado, Zenaide TI Familial long QT syndrome presented as ventricular tachycardia during anesthesia SO PEDIATRIC ANESTHESIA LA English DT Letter ID RISK-FACTORS; SEVOFLURANE; CHILDREN C1 [Tran, Stephanie M.; Nobrega, Raissa Q.; Kammerer, William A.; Quezado, Zenaide] Natl Inst Hlth, Dept Anesthesia & Surg Serv, Ctr Clin, Bethesda, MD 20892 USA. RP Tran, SM (reprint author), Natl Inst Hlth, Dept Anesthesia & Surg Serv, Ctr Clin, Bethesda, MD 20892 USA. EM zquezado@nih.gov RI Quezado, Zenaide/O-4860-2016 OI Quezado, Zenaide/0000-0001-9793-4368 FU Intramural NIH HHS [ZIA CL009009-02] NR 5 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PUBLISHING, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1155-5645 J9 PEDIATR ANESTH JI Pediatr. Anesth. PD JAN PY 2009 VL 19 IS 1 BP 66 EP 68 DI 10.1111/j.1460-9592.2008.02821.x PG 4 WC Anesthesiology; Pediatrics SC Anesthesiology; Pediatrics GA 377RC UT WOS:000261267300030 PM 19076523 ER PT J AU Kelly, KM Thornton, JC Hughes, D Osunkwo, I Weiner, M Wang, J Horlick, M AF Kelly, Kara M. Thornton, John C. Hughes, Deborah Osunkwo, Ifeyinwa Weiner, Michael Wang, Jack Horlick, Mary TI Total Body Bone Measurements: A Cross-Sectional Study in Children With Acute Lymphoblastic Leukemia During and Following Completion of Therapy SO PEDIATRIC BLOOD & CANCER LA English DT Article DE bone mass; bone mineral density; dual-energy X-ray absorptiometry; pediatrics ID X-RAY ABSORPTIOMETRY; LONG-TERM SURVIVORS; MINERAL DENSITY; CRANIAL IRRADIATION; CHILDHOOD; ADOLESCENTS; MASS; PREDNISOLONE; HOMEOSTASIS; OSTEOPENIA AB Background. Abnormalities in bone mineral density (BMD) occur in children treated for acute lymphoblastic leukemia (ALL). However, BMD estimates have been performed using varied instruments, reference data, and interpretations. This exploratory cross sectional study to evaluate bone mass in children with ALL, uses an algorithm that serially adjusts for variables known to affect pediatric bone measures by dual energy X-ray absorptiometry (DXA), based on models developed in 1,218 healthy children and adolescents. Procedure. Anthropometry, DXA scans, and factors with possible influence on bone mass were evaluated in 21 ALL patients receiving chemotherapy and 20 in the follow-up phase. Main Outcome was treatment group differences in Z-scores for total body bone mineral content (BMC), bone area (Area), and areal BMD (aBMD). Results. Mean Z-scores for the entire study population for BMC, Area, and aBMD were significantly less than zero. Among possible contributing factors, only calcium intake was a significant co-variate. Comparison between treatment groups showed that least-square mean Z-scores for patients on-therapy for at least 12 months were significantly lower than those off therapy for at least 12 months (P: 0.0008-0.044), except for BMC at last step of the algorithm (adjusted for sex, age, ethnicity, height, weight, and bone area). Conclusions. Evaluation of total body DXA by this algorithm is consistent with better general bone status in those off-therapy. However, in this small exploratory Study, the lack of significant difference between Z-scores for fully adjusted BMC in on- versus off-therapy groups suggests possible risk of low peak bone mass. Additional longitudinal evaluation is warranted. Pediatr Blood Cancer 2009;52:33-38. (c) 2008 Wiley-Liss, Inc. C1 [Kelly, Kara M.; Hughes, Deborah; Osunkwo, Ifeyinwa; Weiner, Michael] Columbia Univ, Med Ctr, Div Pediat Oncol, Morgan Stanley Childrens Hosp New York Presbyteri, New York, NY 10032 USA. [Thornton, John C.; Wang, Jack] St Lukes Roosevelt Hosp, Body Composit Unit, New York, NY USA. [Horlick, Mary] NIDDK, Div Digest Dis & Nutr, Bethesda, MD USA. RP Kelly, KM (reprint author), Columbia Univ, Med Ctr, Div Pediat Oncol, 161 Ft Washington Ave,Irving Pavil 7, New York, NY 10032 USA. EM kk291@columbia.edu FU Joseph LeRoy and Ann C. Warner Fund, Inc. FX Grant sponsor Joseph LeRoy and Ann C. Warner Fund, Inc. NR 30 TC 10 Z9 10 U1 0 U2 2 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 2009 VL 52 IS 1 BP 33 EP 38 DI 10.1002/pbc.21760 PG 6 WC Oncology; Hematology; Pediatrics SC Oncology; Hematology; Pediatrics GA 378CZ UT WOS:000261300000010 PM 18816694 ER PT J AU Newth, CJL Venkataraman, S Willson, DF Meert, KL Harrison, R Dean, JM Dean, M Pollack, M Zimmerman, J Anand, KJS Carcillo, JA Nicholson, CE AF Newth, Christopher J. L. Venkataraman, Shekhar Willson, Douglas F. Meert, Kathleen L. Harrison, Rick Dean, J. Michael Dean, Michael Pollack, Murray Zimmerman, Jerry Anand, KanwaIjeet J. S. Carcillo, Joseph A. Nicholson, Carol E. CA Eunice Shriver Kennedy Natl Inst C TI Weaning and extubation readiness in pediatric patients SO Pediatric Critical Care Medicine LA English DT Article DE weaning; extubation; mechanical ventilation; respiratory support; spontaneous breathing ID RESPIRATORY-DISTRESS-SYNDROME; ACUTE LUNG INJURY; MECHANICALLY VENTILATED INFANTS; RANDOMIZED CONTROLLED-TRIAL; PREDICTS SUCCESSFUL EXTUBATION; PRESSURE SUPPORT VENTILATION; MAXIMAL INSPIRATORY PRESSURE; PLACEBO-CONTROLLED TRIAL; INTENSIVE-CARE PATIENTS; ENDOTRACHEAL-TUBES AB Objective: A systematic review of weaning and extubation for pediatric patients on mechanical ventilation. Data Selection: Pediatric and adult literature, English language. Study Selection: Invited review. Data Sources: Literature review using National Library of Medicine PubMed from January 1972 until April 2008, earlier cross-referenced article citations, the Cochrane Database of Systematic Reviews, and the Internet. Conclusions: Despite the importance of minimizing time on mechanical ventilation, only limited guidance on weaning and extubation is available from the pediatric literature. A significant proportion of patients being evaluated for weaning are actually ready for extubation, suggesting that weaning is often not considered early enough in the course of ventilation. Indications for extubation are even less clear, although a trial of spontaneous breathing would seem a prerequisite. Several indices have been developed in an attempt to predict weaning and extubation success but the available literature would suggest they offer no improvement over clinical judgment. Extubation failure rates range from 2% to 20% and bear little relationship to the duration of mechanical ventilation. Upper airway obstruction is the single most common cause of extubation failure. A reliable method of assessing readiness for weaning and predicting extubation success is not evident from the pediatric literature. (Pediatr Crit Care Med 2009; 10:1-11) C1 [Newth, Christopher J. L.] Childrens Hosp Los Angeles, Los Angeles, CA 90027 USA. [Venkataraman, Shekhar; Carcillo, Joseph A.] Childrens Hosp Pittsburgh, Pittsburgh, PA 15213 USA. [Willson, Douglas F.] Univ Virginia, Dept Pediat, Childrens Hosp, Charlottesville, VA USA. [Meert, Kathleen L.] Childrens Hosp Michigan, Detroit, MI 48201 USA. [Harrison, Rick] Mattel Childrens Hosp, Los Angeles, CA USA. [Dean, J. Michael] Univ Utah, Dept Pediat, Salt Lake City, UT USA. [Pollack, Murray] Childrens Natl Med Ctr, Washington, DC 20010 USA. [Zimmerman, Jerry] Seattle Childrens Hosp, Seattle, WA USA. [Anand, KanwaIjeet J. S.] Arkansas Childrens Hosp, Little Rock, AR 72202 USA. [Nicholson, Carol E.] NICHHD, Bethesda, MD 20892 USA. RP Newth, CJL (reprint author), Childrens Hosp Los Angeles, Los Angeles, CA 90027 USA. EM cnewth@chla.usc.edu OI Anand, Kanwaljeet/0000-0001-6498-1483 FU NICHD NIH HHS [U10 HD050012, U01 HD049934, U01HD049934, U10 HD049945, U10 HD049981, U10 HD049983, U10 HD050012-01, U10 HD050012-02, U10 HD050012-03, U10 HD050012-04, U10 HD050012-05, U10 HD050012-06, U10 HD050096, U10HD049945, U10HD049981, U10HD049983, U10HD050012, U10HD050096, U10HD500009, UG1 HD050096] NR 87 TC 66 Z9 72 U1 1 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1529-7535 J9 PEDIATR CRIT CARE ME JI Pediatr. Crit. Care Med. PD JAN PY 2009 VL 10 IS 1 BP 1 EP 11 DI 10.1097/PCC.0b013e318193724d PG 11 WC Critical Care Medicine; Pediatrics SC General & Internal Medicine; Pediatrics GA 396EK UT WOS:000262574800001 PM 19057432 ER PT J AU Moss, WJ Scott, S Ndhlovu, Z Monze, M Cults, FT Quinn, TC Griffin, DE AF Moss, William J. Scott, Susana Ndhlovu, Zaza Monze, Mwaka Cults, Felicity T. Quinn, Thomas C. Griffin, Diane E. TI SUPPRESSION OF HUMAN IMMUNODEFICIENCY VIRUS TYPE 1 VIRAL LOAD DURING ACUTE MEASLES SO PEDIATRIC INFECTIOUS DISEASE JOURNAL LA English DT Article DE measles; HIV-1 ID REPLICATION; DYNAMICS; CHILDREN; THERAPY AB Acute measle virus infection call result in a transient decrease in plasma human immunodeficiency virus type 1 (HIV-1) RNA loads. We report the kinetics of plasma HIV-1 RNA loads in 2 Zambian children with confirmed and probable measles, and show that the decline in viral load is of similar magnitude to the first-phase decay rate after initiation of antiretroviral therapy. C1 [Moss, William J.] Johns Hopkins Univ, Bloomberg Sch Publ Hlth, Dept Epidemiol, Baltimore, MD 21218 USA. [Moss, William J.; Ndhlovu, Zaza; Griffin, Diane E.] Johns Hopkins Univ, Bloomberg Sch Publ Hlth, W Harry Feinstone Dept Hlth, Baltimore, MD USA. [Scott, Susana; Cults, Felicity T.] London Sch Hyg & Trop Med, London WC1, England. [Monze, Mwaka] Univ Teaching Hosp, Virol Lab, Lusaka, Zambia. [Quinn, Thomas C.] Johns Hopkins Univ, Sch Med, Div Infect Dis, Baltimore, MD 21205 USA. [Quinn, Thomas C.] NIAID, Natl Inst Hlth, Bethesda, MD 20892 USA. RP Moss, WJ (reprint author), Johns Hopkins Univ, Bloomberg Sch Publ Hlth, Dept Epidemiol, 615 N Wolfe St, Baltimore, MD 21218 USA. EM wmoss@jhsph.edu FU Wellcome Trust-Burroughs Fund Infectious Disease Initiative [GR059114MA]; National Institutes of Health [A123047]; NIAID; National Institutes of Health FX Supported by grant (GR059114MA) from the Wellcome Trust-Burroughs Fund Infectious Disease Initiative, grant A123047 from the National Institutes of Health, and in part by the Division of Intramural Research, NIAID, National Institutes of Health (to T.C.Q.). NR 10 TC 8 Z9 9 U1 0 U2 1 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 2009 VL 28 IS 1 BP 63 EP 65 DI 10.1097/INF.0b013e318184eed2 PG 3 WC Immunology; Infectious Diseases; Pediatrics SC Immunology; Infectious Diseases; Pediatrics GA 391QG UT WOS:000262247200018 PM 19057456 ER PT J AU Castro, M Ramirez, MI Gern, JE Cutting, G Redding, G Hagood, JS Whitsett, J Abman, S Raj, JU Barst, R Kato, GJ Gozal, D Haddad, GG Prabhakar, NR Gauda, E Martinez, FD Tepper, R Wood, RE Accurso, F Teague, WG Venegas, J Cole, FS Wright, RJ AF Castro, Mario Ramirez, Maria I. Gern, James E. Cutting, Garry Redding, Greg Hagood, James S. Whitsett, Jeffrey Abman, Steve Raj, J. Usha Barst, Robyn Kato, Gregory J. Gozal, David Haddad, Gabriel G. Prabhakar, Nanduri R. Gauda, Estelle Martinez, Fernando D. Tepper, Robert Wood, Robert E. Accurso, Frank Teague, W. Gerald Venegas, Jose Cole, F. Sessions Wright, Rosalind J. TI Strategic Plan for Pediatric Respiratory Diseases Research: An NHLBI Working Group Report SO PEDIATRIC PULMONOLOGY LA English DT Article DE epigenetics; pediatric; respiratory; lung disease ID OBSTRUCTIVE SLEEP-APNEA; SICKLE-CELL-DISEASE; GENE-EXPRESSION; LUNG-FUNCTION; EPIGENETIC REGULATION; INTERMITTENT HYPOXIA; RHINOVIRUS ILLNESSES; CONSTANT HYPOXIA; CHILDHOOD ASTHMA; SMOKE EXPOSURE AB The Division of Lung Diseases of the National Heart, Lung and Blood Institute (NHLBI) recently held a workshop to identify gaps in our understanding and treatment of childhood lung diseases and to define strategies to enhance translational research in this field. Leading experts with diverse experience in both laboratory and patient-oriented research reviewed selected areas of pediatric lung diseases, including perinatal programming and epigenetic influences; mechanisms of lung injury, repair, and regeneration; pulmonary vascular disease (PVD); sleep and control of breathing; and the application of novel translational methods to enhance personalized medicine. This report summarizes the proceedings of this workshop and provides recommendations for emphasis on targeted areas for future investigation. The priority areas identified for research in pediatric pulmonary diseases included: (1) epigenetic and environmental influences on lung development that program pediatric lung diseases, (2) injury, regeneration, and repair in the developing lung, (3) PVD in children, (4) development and adaptation of ventilatory responses to postnatal life, (5) nonatopic wheezing: aberrant large airway development or injury? (6) strategies to improve assessment, diagnosis, and treatment of pediatric respiratory diseases, and (7) predictive and personalized medicine for children. PediatrPulmonol.2009;44:2-13. (c) 2008 Wiley-Liss, Inc. C1 [Castro, Mario] Washington Univ, Sch Med, St Louis, MO 63130 USA. [Ramirez, Maria I.] Boston Univ Med, Boston, MA USA. [Gern, James E.] Univ Wisconsin, Madison, WI USA. [Cutting, Garry; Gauda, Estelle] Johns Hopkins Med Inst, Baltimore, MD 21205 USA. [Redding, Greg] Childrens Hosp & Reg Med Ctr, Seattle, WA USA. [Hagood, James S.] Univ Alabama, Birmingham, AL USA. [Whitsett, Jeffrey] Cincinnati Childrens Hosp, Med Ctr, Div Neonatol, Cincinnati, OH USA. [Whitsett, Jeffrey] Cincinnati Childrens Hosp, Med Ctr, Div Pulm Biol, Cincinnati, OH USA. [Abman, Steve] Univ Colorado, Sch Med, Denver, CO USA. [Abman, Steve] Childrens Hosp, Denver, CO 80218 USA. [Raj, J. Usha] Univ Illinois, Chicago, IL USA. [Barst, Robyn] Columbia Univ, New York, NY USA. [Kato, Gregory J.] NHLBI, NIH, Pulm & Vasc Med Branch, Bethesda, MD 20892 USA. [Gozal, David] Univ Louisville, Louisville, KY 40292 USA. [Haddad, Gabriel G.] Univ Calif San Diego, San Diego, CA 92103 USA. [Prabhakar, Nanduri R.] Univ Chicago, Div Biol Sci, Chicago, IL 60637 USA. [Martinez, Fernando D.] Univ Arizona, Coll Med, Tucson, AZ USA. [Tepper, Robert] Indiana Univ, Sch Med, Indianapolis, IN USA. [Accurso, Frank] Univ Colorado, Pulm Med Cyst Fibrosis Ctr, Denver, CO 80202 USA. [Teague, W. Gerald] Emory Univ, Atlanta, GA 30322 USA. [Venegas, Jose] Dept Anesthesia & Crit, Boston, MA USA. [Cole, F. Sessions] Washington Univ, Sch Med, St Louis, MO USA. [Wright, Rosalind J.] Brigham & Womens Hosp, Boston, MA 02115 USA. RP Castro, M (reprint author), Washington Univ, Sch Med, St Louis, MO 63130 USA. RI Kato, Gregory/I-7615-2014 OI Kato, Gregory/0000-0003-4465-3217 NR 77 TC 1 Z9 1 U1 0 U2 0 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 8755-6863 J9 PEDIATR PULM JI Pediatr. Pulmonol. PD JAN PY 2009 VL 44 IS 1 BP 2 EP 13 DI 10.1002/ppul.20973 PG 12 WC Pediatrics; Respiratory System SC Pediatrics; Respiratory System GA 393PV UT WOS:000262386100002 ER PT J AU Olivier, KN AF Olivier, Kenneth N. TI MANAGEMENT OF NONTUBERCULOUS MYCOBATERIA SO PEDIATRIC PULMONOLOGY LA English DT Meeting Abstract ID RAPIDLY GROWING MYCOBACTERIA; COMPLEX LUNG-DISEASE; MACROLIDE RESISTANCE; CYSTIC-FIBROSIS; ABSCESSUS; INFECTION; DIAGNOSIS C1 [Olivier, Kenneth N.] NIAID, Lab Clin Infect Dis, NIH, Bethesda, MD 20892 USA. NR 13 TC 0 Z9 0 U1 0 U2 0 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 8755-6863 J9 PEDIATR PULM JI Pediatr. Pulmonol. PY 2009 MA S81 BP 145 EP 146 PG 2 WC Pediatrics; Respiratory System SC Pediatrics; Respiratory System GA 505OL UT WOS:000270703400029 ER PT J AU Glaser, TS Prevots, DR de Oca, RM Holland, SM Olivier, KN AF Glaser, T. S. Prevots, D. R. de Oca, Montes R. Holland, S. M. Olivier, K. N. TI TOXICITY AND EFFECTIVENESS OF INHALED AMIKACIN FOR REFRACTORY PULMONARY NONTUBERCULOUS MYCOBACTERIAL DISEASE SO PEDIATRIC PULMONOLOGY LA English DT Meeting Abstract C1 [Glaser, T. S.; Prevots, D. R.; de Oca, Montes R.; Holland, S. M.; Olivier, K. N.] NIAID, Lab Clin Infect Dis, NIH, Bethesda, MD 20892 USA. NR 2 TC 0 Z9 0 U1 0 U2 0 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 8755-6863 J9 PEDIATR PULM JI Pediatr. Pulmonol. PY 2009 MA 363 BP 338 EP 339 PG 2 WC Pediatrics; Respiratory System SC Pediatrics; Respiratory System GA 505OL UT WOS:000270703400442 ER PT J AU Tataranni, PA Pannacciulli, N Le, DSNT Del Parigi, A AF Tataranni, P. Antonio Pannacciulli, Nicola Le, Duc Son N. T. Del Parigi, Angelo BE Fruhbeck, G TI Embracing Complexity: The Emergence of Functional Neuroimaging and Other Methodologies to Study the Role of the Human Brain in the Pathophysiology of Obesity SO PEPTIDES IN ENERGY BALANCE AND OBESITY SE Frontiers in Nutritional Science LA English DT Article; Book Chapter ID POSITRON-EMISSION-TOMOGRAPHY; CEREBRAL-BLOOD-FLOW; PRIMATE ORBITOFRONTAL CORTEX; IN-VIVO; EATING-DISORDERS; ENERGY HOMEOSTASIS; ANOREXIA-NERVOSA; GENE-EXPRESSION; FOOD; DOPAMINE C1 [Tataranni, P. Antonio; Pannacciulli, Nicola; Le, Duc Son N. T.; Del Parigi, Angelo] NIDDK, NIH, US Dept HHS, Phoenix, AZ USA. RP Tataranni, PA (reprint author), NIDDK, NIH, US Dept HHS, Phoenix, AZ USA. NR 82 TC 0 Z9 0 U1 0 U2 1 PU CABI PUBLISHING-C A B INT PI WALLINGFORD PA CABI PUBLISHING, WALLINGFORD 0X10 8DE, OXON, ENGLAND BN 978-1-84593-407-1 J9 FRONT NUTR SCI PY 2009 IS 4 BP 309 EP 329 DI 10.1079/9781845934071.0309 PG 21 WC Endocrinology & Metabolism; Physiology SC Endocrinology & Metabolism; Physiology GA BWI65 UT WOS:000293952700013 ER PT J AU Kriegeskorte, N AF Kriegeskorte, N. TI Characterizing categorical and continuous visual-object codes in man, monkey, and computational models with representational similarity analysis SO PERCEPTION LA English DT Meeting Abstract C1 [Kriegeskorte, N.] NIMH, Lab Brain & Cognit, Bethesda, MD 20892 USA. EM kriegeskorten@mail.nih.gov NR 0 TC 0 Z9 0 U1 1 U2 3 PU PION LTD PI LONDON PA 207 BRONDESBURY PARK, LONDON NW2 5JN, ENGLAND SN 0301-0066 J9 PERCEPTION JI Perception PY 2009 VL 38 SU S BP 62 EP 62 PG 1 WC Ophthalmology; Psychology; Psychology, Experimental SC Ophthalmology; Psychology GA V16YN UT WOS:000207905000201 ER PT J AU Yue, X Holt, DJ Cassidy, BS Devaney, KJ Tootell, RBH AF Yue, X. Holt, D. J. Cassidy, B. S. Devaney, K. J. Tootell, R. B. H. TI Face selectivity is parameter-dependent in FFA SO PERCEPTION LA English DT Meeting Abstract C1 [Yue, X.; Devaney, K. J.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Martinos Ctr Biomed Imaging, Boston, MA USA. [Holt, D. J.; Cassidy, B. S.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Psychiat, Boston, MA USA. [Tootell, R. B. H.] NIMH, Lab Brain & Cognit, Bethesda, MD 20892 USA. EM xiaomin@nmr.mgh.harvard.edu 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 2009 VL 38 SU S BP 80 EP 80 PG 1 WC Ophthalmology; Psychology; Psychology, Experimental SC Ophthalmology; Psychology GA V16YN UT WOS:000207905000258 ER PT J AU Maier, A Aura, C Leopold, DA AF Maier, A. Aura, C. Leopold, D. A. TI Visual awareness correlates with layer-specific activity in primary visual cortex SO PERCEPTION LA English DT Meeting Abstract C1 [Maier, A.] NIMH, NIH, Unit Cognit Neurophyiol & Imaging, Birmingham, AL USA. [Leopold, D. A.] NIMH, NIH, Neurophysiol Imaging Facil, LN, Birmingham, AL USA. [Aura, C.] Univ Alabama, Grad Program Neurosci, Birmingham, AL USA. EM maiera@mail.nih.gov RI Maier, Alexander/B-7489-2009 OI Maier, Alexander/0000-0002-7250-502X 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 2009 VL 38 SU S BP 162 EP 162 PG 1 WC Ophthalmology; Psychology; Psychology, Experimental SC Ophthalmology; Psychology GA V16YN UT WOS:000207905000527 ER PT J AU Cumming, B AF Cumming, Bruce TI PMF: Climbing the disparity gradient for twenty years SO PERCEPTION LA English DT Editorial Material ID BINOCULAR DISPARITY; STEREO VISION; LIMIT; TRANSPARENCY; PERCEPTION C1 NIH, Lab Sensory Motor Res, Bethesda, MD 20892 USA. RP Cumming, B (reprint author), NIH, Lab Sensory Motor Res, Bethesda, MD 20892 USA. EM bgc@lsr.nei.nih.gov NR 14 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 2009 VL 38 IS 6 BP 885 EP 887 PG 3 WC Ophthalmology; Psychology; Psychology, Experimental SC Ophthalmology; Psychology GA 479XQ UT WOS:000268695900029 PM 19806977 ER PT J AU Bornstein, MH Gungor, D AF Bornstein, Marc H. Gungor, Derya BA Bekman, S AksuKoc, A BF Bekman, S AksuKoc, A TI Organizing principles and processes from developmental science for culture and caregiving SO PERSPECTIVES ON HUMAN DEVELOPMENT, FAMILY, AND CULTURE LA English DT Article; Book Chapter ID UNITED-STATES; INTERGENERATIONAL TRANSMISSION; CHINESE CHILDREN; JAPAN; FRANCE; SOCIALIZATION; ARGENTINA; TODDLERS; BEHAVIOR; OUTCOMES C1 [Bornstein, Marc H.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Child & Family Res Program Dev Neurosci, Washington, DC USA. [Bornstein, Marc H.] NICHHD, Washington, DC USA. [Gungor, Derya] Univ Louvain, Dept Psychol, Louvain, Belgium. [Gungor, Derya] Univ Utrecht, NL-3508 TC Utrecht, Netherlands. RP Bornstein, MH (reprint author), Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Child & Family Res Program Dev Neurosci, Washington, DC USA. NR 62 TC 0 Z9 0 U1 0 U2 1 PU CAMBRIDGE UNIV PRESS PI CAMBRIDGE PA THE PITT BUILDING, TRUMPINGTON ST, CAMBRIDGE CB2 1RP, CAMBS, ENGLAND BN 978-0-521-87672-8 PY 2009 BP 69 EP 85 DI 10.1017/CBO9780511720437.008 D2 10.1017/CBO9780511720437 PG 17 WC Psychology, Developmental SC Psychology GA BBI90 UT WOS:000306999700007 ER PT B AU Russell, DG Gordon, S AF Russell, David G. Gordon, Siamon BE Russell, DG Gordon, S TI Phagocyte-Pathogen Interactions Macrophages and the Host Response to Infection Preface SO PHAGOCYTE-PATHOGEN INTERACTIONS: MACROPHAGES AND THE HOST RESPONSE TO INFECTION LA English DT Editorial Material; Book Chapter C1 [Russell, David G.] Cornell Univ, Coll Vet Med, Ithaca, NY 14853 USA. [Gordon, Siamon] NCI, NIH, Frederick, MD 21702 USA. [Gordon, Siamon] Univ Oxford, Sir William Dunn Sch Pathol, Oxford OX1 3RE, England. RP Russell, DG (reprint author), Cornell Univ, Coll Vet Med, Ithaca, NY 14853 USA. NR 3 TC 10 Z9 10 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N STREET NW, WASHINGTON, DC 20036-2904 USA BN 978-1-55581-401-4 PY 2009 BP XIII EP XIV PG 2 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA BKL73 UT WOS:000268445000002 ER PT B AU Vinh, DC Holland, SM AF Vinh, Donald C. Holland, Steven M. BE Russell, DG Gordon, S TI Macrophage Classical Activation SO PHAGOCYTE-PATHOGEN INTERACTIONS: MACROPHAGES AND THE HOST RESPONSE TO INFECTION LA English DT Article; Book Chapter ID CHRONIC GRANULOMATOUS-DISEASE; INTERFERON-GAMMA-RECEPTOR; TUMOR-NECROSIS-FACTOR; WISKOTT-ALDRICH-SYNDROME; FACTOR-KAPPA-B; ANHIDROTIC ECTODERMAL DYSPLASIA; MYCOBACTERIAL PHAGOSOME MATURATION; CALMETTE-GUERIN INFECTION; PHAGOCYTIC CUP FORMATION; SMALL DELETION HOTSPOT C1 [Vinh, Donald C.; Holland, Steven M.] NIAID, Immunopathogenesis Sect, Lab Clin Infect Dis, NIH, Bethesda, MD 20892 USA. RP Vinh, DC (reprint author), NIAID, Immunopathogenesis Sect, Lab Clin Infect Dis, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA. NR 202 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N STREET NW, WASHINGTON, DC 20036-2904 USA BN 978-1-55581-401-4 PY 2009 BP 301 EP 323 PG 23 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA BKL73 UT WOS:000268445000021 ER PT B AU Allen, JE Wynn, TA AF Allen, Judith E. Wynn, Thomas A. BE Russell, DG Gordon, S TI Macrophages in Helminth Infection: Effectors, Regulators, and Wound Healers SO PHAGOCYTE-PATHOGEN INTERACTIONS: MACROPHAGES AND THE HOST RESPONSE TO INFECTION LA English DT Article; Book Chapter ID ALTERNATIVELY ACTIVATED MACROPHAGES; NITRIC-OXIDE SYNTHASE; SCHISTOSOMA-MANSONI EGGS; ANTIGEN-PRESENTING CELLS; CD4(+) T-CELLS; MIGRATION INHIBITORY FACTOR; SELECTIVE UP-REGULATION; AMINO-ACID TRANSPORTER; GROWTH-FACTOR-BETA; BRUGIA-MALAYI C1 [Allen, Judith E.] Univ Edinburgh, Inst Evolut Immunol & Infect Res, Edinburgh EH9 3JT, Midlothian, Scotland. [Wynn, Thomas A.] NIAID, Immunopathogenesis Sect, NIH, Bethesda, MD 20892 USA. RP Allen, JE (reprint author), Univ Edinburgh, Inst Evolut Immunol & Infect Res, Edinburgh EH9 3JT, Midlothian, Scotland. NR 170 TC 0 Z9 0 U1 0 U2 2 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N STREET NW, WASHINGTON, DC 20036-2904 USA BN 978-1-55581-401-4 PY 2009 BP 477 EP 490 PG 14 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA BKL73 UT WOS:000268445000033 ER PT J AU Betz, JM AF Betz, Joseph M. TI SAFETY, CAUSALITY, AND ASSOCIATION: CHALLENGES IN INVESTIGATING ADVERSE EVENTS SO PHARMACEUTICAL BIOLOGY LA English DT Meeting Abstract C1 [Betz, Joseph M.] NIH, Off Dietary Supplements, Bethesda, MD 20892 USA. EM betzj@od.nih.gov NR 0 TC 0 Z9 0 U1 0 U2 0 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 325 CHESTNUT ST, SUITE 800, PHILADELPHIA, PA 19106 USA SN 1388-0209 J9 PHARM BIOL JI Pharm. Biol. PY 2009 VL 47 BP 14 EP 15 PG 2 WC Plant Sciences; Medical Laboratory Technology; Pharmacology & Pharmacy SC Plant Sciences; Medical Laboratory Technology; Pharmacology & Pharmacy GA 403OZ UT WOS:000263093200039 ER PT J AU Cardellina, JH AF Cardellina, John H., II TI BLACK COHOSH: CONSIDERATIONS OF SAFETY AND BENEFIT SO PHARMACEUTICAL BIOLOGY LA English DT Meeting Abstract C1 [Cardellina, John H., II] NIH, Off Dietary Supplements, Bethesda, MD 20892 USA. EM jhcardellina@aol.com NR 0 TC 0 Z9 0 U1 0 U2 0 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 325 CHESTNUT ST, SUITE 800, PHILADELPHIA, PA 19106 USA SN 1388-0209 J9 PHARM BIOL JI Pharm. Biol. PY 2009 VL 47 BP 22 EP 22 PG 1 WC Plant Sciences; Medical Laboratory Technology; Pharmacology & Pharmacy SC Plant Sciences; Medical Laboratory Technology; Pharmacology & Pharmacy GA 403OZ UT WOS:000263093200060 ER PT J AU Betz, JM Saldanha, LG Fisher, KD Coates, PM Klein, M Engel, J Pho, AN Sharpless, KE Sander, LC Wise, SA Rimmer, CA Phinney, K AF Betz, J. M. Saldanha, L. G. Fisher, K. D. Coates, P. M. Klein, M. Engel, J. Pho, A. Nguyen Sharpless, K. E. Sander, L. C. Wise, S. A. Rimmer, C. A. Phinney, K. TI THE NIH/ODS ANALYTICAL METHODS AND REFERENCE MATERIALS PROGRAM FOR DIETARY SUPPLEMENTS: FIVE-YEAR ACCOMPLISHMENTS AND FUTURE DIRECTIONS SO PHARMACEUTICAL BIOLOGY LA English DT Meeting Abstract C1 [Betz, J. M.; Saldanha, L. G.; Fisher, K. D.; Coates, P. M.; Klein, M.; Engel, J.] NIH, Off Dietary Supplements, Bethesda, MD 20892 USA. [Pho, A. Nguyen] US FDA, Silver Spring, MD 20993 USA. [Sharpless, K. E.; Sander, L. C.; Wise, S. A.; Rimmer, C. A.; Phinney, K.] Natl Inst Stand & Technol, Gaithersburg, MD 20899 USA. EM betzj@od.nih.gov NR 0 TC 0 Z9 0 U1 0 U2 0 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 325 CHESTNUT ST, SUITE 800, PHILADELPHIA, PA 19106 USA SN 1388-0209 J9 PHARM BIOL JI Pharm. Biol. PY 2009 VL 47 BP 29 EP 29 PG 1 WC Plant Sciences; Medical Laboratory Technology; Pharmacology & Pharmacy SC Plant Sciences; Medical Laboratory Technology; Pharmacology & Pharmacy GA 403OZ UT WOS:000263093200079 ER PT J AU Hirunsatit, R George, ED Lipska, BK Elwafi, HM Sander, L Yrigollen, CM Gelernter, J Grigorenko, EL Lappalainen, J Mane, S Nairn, AC Kleinman, JE Simen, AA AF Hirunsatit, Rungnapa George, Elizabeth D. Lipska, Barbara K. Elwafi, Hani M. Sander, Lisa Yrigollen, Carolyn M. Gelernter, Joel Grigorenko, Elena L. Lappalainen, Jaakko Mane, Shrikant Nairn, Angus C. Kleinman, Joel E. Simen, Arthur A. TI Twenty-one-base-pair insertion polymorphism creates an enhancer element and potentiates SLC6A1 GABA transporter promoter activity SO PHARMACOGENETICS AND GENOMICS LA English DT Article DE African continental ancestry group; enhancer elements; gamma-aminobutyric acid plasma membrane transport proteins; transcription factors; zinc fingers ID MAGNETIC-RESONANCE-SPECTROSCOPY; TRANSCRIPTION FACTOR ZBP-89; DEPRESSED-PATIENTS; UPTAKE INHIBITOR; GENE-EXPRESSION; VIMENTIN GENE; OPEN-LABEL; TIAGABINE; ANXIETY; BRAIN AB Objective Sodium-dependent and chloride-dependent gamma-aminobutyric acid (GABA) transporter 1 (SLC6A1) is the target of a number of drugs of clinical importance and is a major determinant of synaptic GABA concentrations. We resequenced the human SLC6A1 gene previously and discovered a novel 21 bp insertion in the predicted promoter region that creates a second tandem copy of the sequence. Here we sought to determine the functional relevance of this variation. Methods We used reporter assays, mobility shift assays, quantitative PCR, and proteomics methods as well as postmortem expression analysis for this work. Results Reporter assays showed that the insertion allele significantly increases promoter activity in multiple cell lines. The zinc finger transcription factor ZNF148 was found to significantly transactivate the promoter and increase expression when overexpressed but could not account for the differences in activity between the two alleles of the promoter. Copy number of the insertion sequence was associated with exponentially increasing activity of a downstream promoter, suggesting that the insertion sequence has enhancer activity when present in multiple copies. SLC6A1 promoter genotype was found to predict SLC6A1 RNA expression in human postmortem hippocampal samples. These results suggest that the insertion polymorphism leads to increased SLC6A1 promoter activity because, in part, of creation of an enhancer element when present as multiple copies. Genotyping individuals from Tanzania in this study suggested that the insertion allele has its origin in Africa. Conclusion On account of the effect of the insertion on promoter activity, this relatively common polymorphism may prove useful in predicting clinical response to pharmacological modulators of SLC6A1 as well as GABAergic function in individuals of African descent. Pharmacogenetics and Genomics 19:53-65 (C) 2009 Wolters Kluwer Health | Lippincott Williams & Wilkins. C1 [Simen, Arthur A.] Yale Univ, Sch Med, Div Mol Psychiat, Dept Psychiat, New Haven, CT 06511 USA. [Yrigollen, Carolyn M.; Grigorenko, Elena L.] Yale Univ, Sch Med, Psychol & Child Study Ctr, New Haven, CT 06511 USA. [Mane, Shrikant] Yale Univ, Sch Med, Yale Keck Ctr, New Haven, CT 06511 USA. [Hirunsatit, Rungnapa; Gelernter, Joel; Lappalainen, Jaakko] VA Connecticut Healthcare Syst, West Haven, CT USA. [Lipska, Barbara K.; Kleinman, Joel E.] NIMH, Sect Neuropathol, Clin Brain Disorders Branch, GCAP,IRP,NIH, Bethesda, MD 20892 USA. RP Simen, AA (reprint author), Yale Univ, Sch Med, Div Mol Psychiat, Dept Psychiat, Suite 901, New Haven, CT 06511 USA. EM Arthur.Simen@yale.edu OI Nairn, Angus/0000-0002-7075-0195 FU NIH [D43 TW06166, 1KL2RR024138, T32-MH14276, U24 NS051869]; VA REAP Award; NCRR [RR19895]; NARSAD Young Investigator Award; NIDA [DA018343]; Fogarty Program [TW006764]; NICHD; Yale/NIDA Proteomics Center FX R.H. was supported by NIH grant D43 TW06166 and a VA REAP Award. A.S. was supported by NIH grant 1KL2RR024138, NCRR grant RR19895, a NARSAD Young Investigator Award, and a VA REAP Award. A.S. and A.N. were supported by NIDA grant DA018343. L.D.G. was supported by NIH grant T32-MH14276. E.L.G. and C.Y were supported by grant TW006764 (PI: Grigorenko) from the Fogarty Program, NIH and HD048830 (PI: Pugh) from NICHD. J.G. was supported in part by a VA REAP Award. The authors would like to acknowledge the support of the Yale/NIH Neuroscience Microarray Center supported by NIH grant U24 NS051869. The authors thank Kathy Stone and Terence Wu from the Yale/NIDA Proteomics Center as well as Maya M. Davis. We thank Dr Thomas M. Hyde for his Involvement in creating the brain collection and his neuroanatomical expertise, and Ms Samhita Kumar and Mr Ross Buerlein for their technical support. NR 33 TC 13 Z9 14 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1744-6872 J9 PHARMACOGENET GENOM JI Pharmacogenet. Genomics PD JAN PY 2009 VL 19 IS 1 BP 53 EP 65 DI 10.1097/FPC.0b013e328318b21a PG 13 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Pharmacology & Pharmacy SC Biotechnology & Applied Microbiology; Genetics & Heredity; Pharmacology & Pharmacy GA 393AE UT WOS:000262342500006 PM 19077666 ER PT J AU Surh, LC Lesko, LJ Hobbs, S Gutman, S Minasian, LM Della Pasqua, OE Austin, MJF Lu, K AF Surh, Linda C. Lesko, Lawrence J. Hobbs, Stuart Gutman, Steve Minasian, Lori M. Della Pasqua, Oscar E. Austin, M. J. Finley Lu, Kan TI Fit-for-purpose pharmacogenomic biomarkers in drug development: a project team case study with 'what-ifs' SO PHARMACOGENOMICS LA English DT Article DE biomarkers; drug development; pharmacogenetics; pharmacogenomics; Product Label; SPC; Summary of Product Characteristics; USPI; US Prescribing Information AB Over the past four years, the annual US FDA-DIA pharmacogenomic workshops have brought together attendees with wide-ranging expertise spanning industry, regulatory authorities and academia. This special report summarizes a breakout session using a novel, interactive case format as a way to engage participants, raise awareness and share diverse learnings via 'real life' decisions that project teams might face in developing a new medicine. This case was situated just prior to approval by a Regulatory Authority as a project team is finalizing a new medicine label. To effectively integrate new biomarkers such as pharmacogenomics into developing new medicines, this session highlighted the importance in considering medical practice implications as relevant (or not) to information or actions by a prescriber; progressing validation beyond assay to clinical; and fitting pharmacogenomics into context with other evidence often built over decades during a drug's development. All converge onto a label that must communicate evidence-based use of a new medicine that is effective and safe. C1 [Surh, Linda C.] GlaxoSmithKline Inc, CEDD, Global Regulatory Affairs Neurol & Pharmacogenet, Greenford UB6 0HE, Middx, England. [Lesko, Lawrence J.] US FDA, Off Clin Pharmacol, CDER, Rockville, MD 20857 USA. [Hobbs, Stuart; Lu, Kan] GlaxoSmithKline Inc, Strateg Prod Labelling, Res Triangle Pk, NC USA. [Gutman, Steve] US FDA, Off In Vitro Diagonost, CDRH, Rockville, MD 20857 USA. [Minasian, Lori M.] NCI, NIH, Bethesda, MD 20892 USA. [Della Pasqua, Oscar E.] GlaxoSmithKline Inc, Res Triangle Pk, NC USA. RP Surh, LC (reprint author), GlaxoSmithKline Inc, CEDD, Global Regulatory Affairs Neurol & Pharmacogenet, Greenford Rd, Greenford UB6 0HE, Middx, England. EM lcs29779@gsk.com NR 4 TC 4 Z9 5 U1 0 U2 0 PU FUTURE MEDICINE LTD PI LONDON PA UNITEC HOUSE, 3RD FLOOR, 2 ALBERT PLACE, FINCHLEY CENTRAL, LONDON, N3 1QB, ENGLAND SN 1462-2416 J9 PHARMACOGENOMICS JI Pharmacogenomics PD JAN PY 2009 VL 10 IS 1 BP 137 EP 147 DI 10.2217/14622416.10.1.137 PG 11 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 396BR UT WOS:000262567700019 PM 19102723 ER PT J AU Greenwell, TN Walker, BM Cottone, P Zorrilla, EP Koob, GF AF Greenwell, Thomas N. Walker, Brendan M. Cottone, Pietro Zorrilla, Eric P. Koob, George F. TI The alpha(1) adrenergic receptor antagonist prazosin reduces heroin self-administration in rats with extended access to heroin administration SO PHARMACOLOGY BIOCHEMISTRY AND BEHAVIOR LA English DT Article DE Drug abuse; Escalation; Opiate; Norepinephrine; alpha-1 receptor ID PHENYLPROPANOLAMINE-INDUCED ANOREXIA; CORTICOTROPIN-RELEASING-FACTOR; POSTTRAUMATIC-STRESS-DISORDER; OPIATE-WITHDRAWAL; STRIA TERMINALIS; DEPENDENT RATS; BED NUCLEUS; FEEDING PATTERNS; COCAINE SEEKING; LOCUS-COERULEUS AB Previous studies have reported that noradrenergic antagonists alleviate some of the symptoms of opiate withdrawal and dependence. Clinical studies also have shown that modification of the noradrenergic system may help protect patients from relapse. The present study tested the hypothesis that a dysregulated noradrenergic system has motivational significance in heroin self-administration of dependent rats. Prazosin. an alpha(1)-adrenergic antagonist (0.5, 1.0, 1.5 and 2.0 mg/kg, i.p.), was administered to adult male Wistar rats with a history of limited (1 h/day: short access) or extended (12 h/day; long access) access to intravenous heroin self-administration. Prazosin dose-dependently reduced heroin self-administration in long-access rats but not short-access rats, with 2 mg/kg of systemic prazosin significantly decreasing 1 and 2 h heroin intake. Prazosin also reversed some changes in meal pattern associated with extended heroin access. including the taking of smaller and briefer meals (at 3 h), while also increasing total food intake and slowing the eating rate within meals (both 3 h and 12 h). Thus. prazosin appears to stimulate food intake in extended access rats by restoring meals to the normal size and duration. The data Suggest that the alpha(1) adrenergic system may contribute to mechanisms that promote dependence in rats with extended access. (c) 2008 Elsevier Inc. All rights reserved. C1 [Greenwell, Thomas N.; Walker, Brendan M.; Cottone, Pietro; Zorrilla, Eric P.; Koob, George F.] Scripps Res Inst, Comm Neurobiol Addict Disorders, La Jolla, CA 92037 USA. RP Greenwell, TN (reprint author), NIAAA, Div Neurosci & Behav, 5635 Fishers Lane,Room 2052,MSC 9304, Bethesda, MD 20892 USA. EM greenwellt@mail.nih.gov RI Cottone, Pietro/F-5291-2012; Walker, Brendan /B-9219-2011; koob, george/P-8791-2016; OI Cottone, Pietro/0000-0003-1320-1672; Walker, Brendan /0000-0002-7217-3950; Greenwell, Thomas/0000-0001-6069-0064 FU National Institutes of Health [DA019295]; National Institute on Drug Abuse [DA004043]; Pearson Center for Alcoholism and Addiction Research FX Supported by National Institutes of Health grants DA019295 (1732 to TNG) and DA004043 (GFK) from the National Institute on Drug Abuse and the Pearson Center for Alcoholism and Addiction Research. The authors thank Mr. Robert Lititz for excellent technical assistance and Mr. Michael Arends for editorial assistance. NR 58 TC 29 Z9 29 U1 1 U2 3 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0091-3057 J9 PHARMACOL BIOCHEM BE JI Pharmacol. Biochem. Behav. PD JAN PY 2009 VL 91 IS 3 BP 295 EP 302 DI 10.1016/j.pbb.2008.07.012 PG 8 WC Behavioral Sciences; Neurosciences; Pharmacology & Pharmacy SC Behavioral Sciences; Neurosciences & Neurology; Pharmacology & Pharmacy GA 402LF UT WOS:000263014500005 PM 18703080 ER PT J AU May, JA Sharif, NA Chen, HH Liao, JC Kelly, CR Glennon, RA Young, R Li, JX Rice, KC France, CR AF May, Jesse A. Sharif, Najam A. Chen, Hwang-Hsing Liao, John C. Kelly, Curtis R. Glennon, Richard A. Young, Richard Li, Jun-Xu Rice, Kenner C. France, Charles R. TI Pharmacological properties and discriminative stimulus effects of a novel and selective 5-HT2 receptor agonist AL-38022A [(S)-2-(8,9-dihydro-7H-pyrano[2,3-g]indazol-1-yl)-1-methylethylamine] SO PHARMACOLOGY BIOCHEMISTRY AND BEHAVIOR LA English DT Article DE Drug discrimination; 5-HT2 receptor; R-DOI; DOM; MDL 100907; Rat; Monkey ID OCULAR HYPOTENSIVE ACTIVITY; RELATIVE EFFICACY; BINDING; ACTIVATION; LIGANDS; CELLS; RAT; DOM; HALLUCINOGENS; ANTAGONIST AB AL-38022A is a novel synthetic serotonergic (5-HT) ligand that exhibited high affinity for each of the 5-HT2 receptor subtypes (K-i <= 2.2 nM), but a significantly lower (> 100-fold less) affinity for other 5-HT receptors. In addition, AL-38022A displayed a very low affinity for a broad array of other receptors, neurotransmitter transport sites, ion channels, and second messenger elements, making it a relatively selective agent. AL-38022A potently stimulated functional responses via native and cloned rat (EC50 range: 1.9-22.5 nM) and human (EC5o range: 0.5-2.2 nM) 5-HT2 receptor subtypes including [Ca2+](i) mobilization and tissue contractions with apparently similar potencies and intrinsic activities and was a full agonist at all 5-HT2 receptor subtypes. The CNS activity of AL-38022A was assessed by evaluating its discriminative stimulus effects in both a rat and a monkey drug discrimination paradigm using DOM as the training drug. AL-38022A fully generalized to the DOM stimulus in each of these Studies; in monkeys MDL 100907 antagonized both DOM and AL-38022A. The pharmacological profile of AL-38022A suggests that it could be a useful tool in defining 5-HT2 receptor signaling and receptor characterization where 5-HT may function as a neurotransmitter. (c) 2008 Elsevier Inc, All rights reserved. C1 [May, Jesse A.; Sharif, Najam A.; Chen, Hwang-Hsing; Liao, John C.; Kelly, Curtis R.] Alcon Res Ltd, Ophthalmol Discovery, Ft Worth, TX 76134 USA. [Glennon, Richard A.; Young, Richard] Virginia Commonwealth Univ, Dept Med Chem, Sch Pharm, Richmond, VA 23298 USA. [Li, Jun-Xu; France, Charles R.] Univ Texas Hlth Sci Ctr San Antonio, Dept Pharmacol, San Antonio, TX 78229 USA. [Rice, Kenner C.] NIDA, Chem Biol Res Branch, NIH, Bethesda, MD 20892 USA. [Rice, Kenner C.] NIAAA, NIH, Bethesda, MD 20892 USA. RP May, JA (reprint author), Alcon Res Ltd, Ophthalmol Discovery, Mail Stop R2-39,6201 South Freeway, Ft Worth, TX 76134 USA. EM jesse.may@alconlabs.com RI Li, Jun-Xu/K-9192-2013 FU Intramural research Program of the NIDA; NIAAA; NIDDKD FX The authors thank Parvaneh Katoli, Gary Williams, and Shouxi Xu of ARL Molecular Pharmacology Unit for their expert technical assistance. We thank Dr. Philip Kastner of ARL In Vivo Pharmacology Unit for helpful discussions. Organix, Inc., Woburn, MA, conducted scale-up synthesis. This research was supported in part by the Intramural research Program of the NIDA, the NIAAA and the NIDDKD. NR 40 TC 6 Z9 6 U1 0 U2 3 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0091-3057 J9 PHARMACOL BIOCHEM BE JI Pharmacol. Biochem. Behav. PD JAN PY 2009 VL 91 IS 3 BP 307 EP 314 DI 10.1016/j.pbb.2008.07.015 PG 8 WC Behavioral Sciences; Neurosciences; Pharmacology & Pharmacy SC Behavioral Sciences; Neurosciences & Neurology; Pharmacology & Pharmacy GA 402LF UT WOS:000263014500007 PM 18718483 ER PT J AU Mathur, P Graybeal, C Feyder, M Davis, MI Holmes, A AF Mathur, Poonam Graybeal, Carolyn Feyder, Michael Davis, Margaret I. Holmes, Andrew TI Fear memory impairing effects of systemic treatment with the NMDA NR2B subunit antagonist, Ro 25-6981, in mice: Attenuation with ageing SO PHARMACOLOGY BIOCHEMISTRY AND BEHAVIOR LA English DT Article DE Aged; Anxiety; Glutamate; Learning; Memory; NR2A; Prepulse inhibition; Open field; Elevated plus-maze; One-trial; Western blot; C57BL/6 ID LONG-TERM-POTENTIATION; RECEPTOR EPSILON-1 SUBUNIT; AGE-RELATED-CHANGES; SYNAPTIC PLASTICITY; LATERAL AMYGDALA; BASOLATERAL AMYGDALA; TETRAMERIC STRUCTURE; PREPULSE INHIBITION; ALZHEIMERS-DISEASE; VISUAL-CORTEX AB N-methyl-D-aspartate receptors (NMDARs) are mediators of synaptic plasticity and learning and are implicated in the pathophysiology Of neuropsychiatric disease and age-related cognitive dysfunction. NMDARs are heteromers, but the relative contribution of specific subunits to NMDAR-mediated learning is not fully understood. We characterized pre-conditioning systemic treatment of the NR2B subunit-selective antagonist Ro 25-6981 for effects on multi-trial, one-trial and low-shock Pavlovian fear conditioning in C57BL/6J mice. Ro 25-6981 was also profiled for effects on novel open field exploration, elevated plus-maze anxiety-like behavior, startle reactivity, prepulse inhibition of startle, and nociception. Three-month (adult) and 12-month old C57BL/6Tac mice were compared for Ro 25-6981 effects on multi-trial fear conditioning. and corticolimbic NR2B protein levels. Ro 25-6981 moderately impaired fear learning in the multi-trial and one-trial (but not low-shock) conditioning paradigms, but did not affect exploratory or anxiety-related behaviors or sensory functions. Memory impairing effects of Ro 25-6981 were absent in 12-month old mice, although NR2B protein levels were not significantly altered. Present data provide further evidence of the memory impairing effects of selective blockade of NR2B-containing NMDARs, and show loss of these effects with ageing. This work could ultimately have implications for elucidating the pathophysiology of learning dysfunction in neuropsychiatric disorders and ageing. Published by Elsevier Inc. C1 [Mathur, Poonam; Graybeal, Carolyn; Feyder, Michael; Holmes, Andrew] NIAAA, Sect Behav Sci & Genet, Lab Integrat Neurosci, Rockville, MD 20852 USA. [Davis, Margaret I.] NIAAA, Sect Synapt Pharmacol, Lab Integrat Neurosci, Rockville, MD 20852 USA. RP Holmes, A (reprint author), NIAAA, Sect Behav Sci & Genet, Lab Integrat Neurosci, 5625 Fishers Lane,Room 2N09, Rockville, MD 20852 USA. EM holmesan@mail.nih.gov RI Davis, Margaret/F-4165-2010; OI Davis, Margaret/0000-0002-0489-8351 FU National Institute of Alcohol Abuse and Alcoholism [Z01-AA000411] FX We would like to thank Dr. Stan Floresco for comments on an earlier version of the manuscript. Research Supported by the Intramural Research Program of the National Institute of Alcohol Abuse and Alcoholism (Z01-AA000411). NR 83 TC 20 Z9 25 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0091-3057 J9 PHARMACOL BIOCHEM BE JI Pharmacol. Biochem. Behav. PD JAN PY 2009 VL 91 IS 3 BP 453 EP 460 DI 10.1016/j.pbb.2008.08.028 PG 8 WC Behavioral Sciences; Neurosciences; Pharmacology & Pharmacy SC Behavioral Sciences; Neurosciences & Neurology; Pharmacology & Pharmacy GA 402LF UT WOS:000263014500029 PM 18809426 ER PT J AU Estes, KE Penzak, SR Calis, KA Walsh, TJ AF Estes, Kristina E. Penzak, Scott R. Calis, Karim Anton Walsh, Thomas J. TI Pharmacology and Antifungal Properties of Anidulafungin, a New Echinocandin SO PHARMACOTHERAPY LA English DT Review DE anidulafungin; echinocandins; candidemia; invasive candidiasis; esophageal candidiasis ID PERSISTENTLY NEUTROPENIC RABBITS; EXPERIMENTAL PULMONARY ASPERGILLOSIS; IN-VITRO; MICAFUNGIN FK463; INVASIVE ASPERGILLOSIS; CANDIDA-ALBICANS; ESOPHAGEAL CANDIDIASIS; DOSE PHARMACOKINETICS; AMPHOTERICIN-B; CASPOFUNGIN AB Anidulafungin is the third echinocandin antifungal agent to receive approval from the United States Food and Drug Administration. It is indicated for the treatment of esophageal candidiasis, candidemia, and other candidal infections. Anidulafungin is fungicidal against Candida species, including Candida glabrata and isolates resistant to azoles and. polyenes. The drug's efficacy is comparable to that of fluconazole for the treatment of esophageal candidiasis, and it is effective in patients with invasive candidiasis and candidemia. Anidulafungin is distinct among the echinocandins in that it undergoes slow, nonenzymatic chemical degradation. As a consequence, impairments in renal or hepatic function do not substantially alter its pharmacokinetics. In addition, anidulafungin has not demonstrated any drug-drug interactions because it is not a substrate, inhibitor, or inducer of the cytochrome P450 enzyme system. Anidulafungin is well tolerated ill adults and pediatric patients, with few reported adverse drug events. The safety, tolerability, and potent fungicidal activity of anidulafungin against Candida species make it a reasonable alternative in the treatment of patients with serious candidal infections. C1 [Walsh, Thomas J.] NCI, Immunocompromised Host Sect, Pediat Oncol Branch, Bethesda, MD 20892 USA. [Estes, Kristina E.; Penzak, Scott R.; Calis, Karim Anton] NCI, Ctr Clin, Dept Pharm, NIH, Bethesda, MD 20892 USA. RP Walsh, TJ (reprint author), NCI, Immunocompromised Host Sect, Pediat Oncol Branch, 10 Ctr Dr,1-5740, Bethesda, MD 20892 USA. NR 66 TC 16 Z9 17 U1 1 U2 3 PU PHARMACOTHERAPY PUBLICATIONS INC PI BOSTON PA NEW ENGLAND MEDICAL CENTER, 806, 750 WASHINGTON ST, BOSTON, MA 02111 USA SN 0277-0008 J9 PHARMACOTHERAPY JI Pharmacotherapy PD JAN PY 2009 VL 29 IS 1 BP 17 EP 30 PG 14 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 392HS UT WOS:000262294400004 PM 19113794 ER PT J AU Kwok, RK Linet, MS Chodick, G Kleinerman, RA Freedman, DM Fears, T Johnson, RE Alexander, BH AF Kwok, Richard K. Linet, Martha S. Chodick, Gabriel Kleinerman, Ruth A. Freedman, Daryl M. Fears, Tom Johnson, Ruby E. Alexander, Bruce H. TI Simplified Categorization of Outdoor Activities for Male and Female US Indoor Workers-A Feasibility Study to Improve Assessment of Ultraviolet Radiation Exposures in Epidemiologic Study Questionnaires SO PHOTOCHEMISTRY AND PHOTOBIOLOGY LA English DT Article ID SKIN-CANCER; RADIOLOGIC TECHNOLOGISTS; MULTIPLE-SCLEROSIS; UV-RADIATION; SUN EXPOSURE; VITAMIN-D; MELANOMA; SUNLIGHT; RISK; RELIABILITY AB Skin cancer studies depend on questionnaires to estimate exposure to ultraviolet light and subsequent risk but are limited by recall bias. We investigate the feasibility of developing a short checklist of categories comprising outdoor activities that can improve sun exposure questionnaires for use in epidemiologic studies. We recruited 124 working and retired U.S. radiologic technologists (52% women). Each subject was instructed to complete a daily activity diary, listing main indoor and outdoor activities between 9:00 A.M. and 5:00 P.M. during a 7 day period. A total of 4697 entries were associated with 1408 h (21.1%) of the total 6944 h spent outdoors. We were able to classify the activities into seven main activity categories: driving, yard work, home-maintenance, walking or performing errands, water activities, other recreational or sports activities and leisure activities or relaxing outside. These activities accounted for more than 94% of time spent outdoors both for working and retired men and women. Our data document the feasibility and guidance for developing a short checklist of outdoor activities for use in epidemiologic questionnaires for estimating sunlight exposures of working and retired indoor workers. C1 [Kwok, Richard K.; Johnson, Ruby E.] RTI Int, Stat & Epidemiol Div, Res Triangle Pk, NC USA. [Linet, Martha S.; Chodick, Gabriel; Kleinerman, Ruth A.; Freedman, Daryl M.] NCI, Radiat Epidemiol Branch, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. [Fears, Tom] NCI, Biostat Branch, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. [Alexander, Bruce H.] Univ Minnesota, Div Environm Hlth Sci, Minneapolis, MN USA. RP Kwok, RK (reprint author), RTI Int, Stat & Epidemiol Div, Res Triangle Pk, NC USA. EM rkwok@rti.org RI Kwok, Richard/B-6907-2017; OI Kwok, Richard/0000-0002-6794-8360; Kleinerman, Ruth/0000-0001-7415-2478 FU National Cancer Institute [N02-CP-31013] FX The authors gratefully acknowledge the participation of the USRT cohort members. Thanks to Michael Phillips, Emily McFarlane, Colleen Waters (RTI) and Diane Kampa (U Minnesota) for their assistance. This work was supported by Contract N02-CP-31013 with the National Cancer Institute. There are no other competing financial interests. This study has been conducted in accord with accepted ethical and humane practices, and has been approved by the pertinent institutional and/or governmental oversight group(s). NR 29 TC 6 Z9 7 U1 0 U2 4 PU WILEY-BLACKWELL PUBLISHING, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0031-8655 J9 PHOTOCHEM PHOTOBIOL JI Photochem. Photobiol. PD JAN-FEB PY 2009 VL 85 IS 1 BP 45 EP 49 DI 10.1111/j.1751-1097.2008.00393.x PG 5 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 394XP UT WOS:000262486800005 PM 18643910 ER PT J AU Smith, MR Hildenbrand, H Smith, ACM AF Smith, Michaele R. Hildenbrand, Hanna Smith, Ann C. M. TI Sensory Motor and Functional Skills of Dizygotic Twins: One with Smith-Magenis Syndrome and a Twin Control SO PHYSICAL & OCCUPATIONAL THERAPY IN PEDIATRICS LA English DT Article DE Fine motor; genetic disorder; gross motor; sensory processing ID SYNDROME DEL 17P11.2; MALADAPTIVE BEHAVIOR; CHILDREN; (17)(P11.2P11.2); PHENOTYPE; PROFILES AB Smith-Magenis syndrome (SMS), the result of an interstitial deletion within chromosome 17p11.2, is a disorder that may include minor dysmorphic features, brachydactyly, short stature, hypotonia, speech delays, cognitive deficits, signs of peripheral neuropathy, scoliosis, and neurobehavioral problems including sleep disturbances and maladaptive repetitive and self-injurious behaviors. Physical and occupational therapists provide services for children who have the syndrome, whose genetic disorder is frequently not identified or diagnosed before 1 year of age. A comprehensive physical and occupational therapy evaluation was completed in nonidentical twins with one having SMS, using the Sensory Profile; Brief Assessment of Motor Function (BAMF); Peabody Developmental Motor Scales, Second Edition (PDMS-2); and Pediatric Evaluation of Disability Inventory (PEDI). This provides a framework for conducting assessments to enhance early detection and interdisciplinary management with this specialized population. C1 [Smith, Michaele R.; Hildenbrand, Hanna] NIH, Dept Rehabil Med, Bethesda, MD 20892 USA. [Smith, Ann C. M.] NHGRI, NIH, Bethesda, MD 20892 USA. [Smith, Ann C. M.] Georgetown Univ, Sch Med, Washington, DC 20057 USA. RP Smith, MR (reprint author), NIH, Dept Rehabil Med, Bldg 10-CRC,Room 1-1469 NE, Bethesda, MD 20892 USA. EM Msmith@cc.nih.gov FU National Human Genome Research Institute, NIH; NIH Clinical Center FX This research was supported in part by the Intramural Research Program of the National Human Genome Research Institute, NIH, and the NIH Clinical Center's Bench-to-Bedside Award. The authors gratefully acknowledge the parents and children who participated in this study and the internal reviewers from the Rehabilitation Medicine Department. The opinions and information contained in this paper are those of the authors and do not necessarily reflect those of the NIH or the U. S. Public Health Service. NR 33 TC 1 Z9 1 U1 0 U2 2 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 2009 VL 29 IS 3 BP 239 EP 257 DI 10.1080/01942630903028408 PG 19 WC Pediatrics; Rehabilitation SC Pediatrics; Rehabilitation GA V19BD UT WOS:000208047000004 PM 19842854 ER PT J AU Thanos, PK Cavigelli, SA Michaelides, M Olvet, DM Patel, U Diep, MN Volkow, ND AF Thanos, P. K. Cavigelli, S. A. Michaelides, M. Olvet, D. M. Patel, U. Diep, M. N. Volkow, N. D. TI A Non-Invasive Method for Detecting the Metabolic Stress Response in Rodents: Characterization and Disruption of the Circadian Corticosterone Rhythm SO PHYSIOLOGICAL RESEARCH LA English DT Article DE Corticosterone; Stress; Fecal steroid metabolites; Circadian rhythm ID MALE RATS; IMMUNOGLOBULIN-A; EXCRETION; PATTERNS; COCAINE; URINE; FECES; TIME; MICE; SEX AB Plasma corticosterone (CORT) measures are a common procedure to detect stress responses in rodents. However, the procedure is invasive and can influence CORT levels, making it less than ideal for monitoring CORT circadian rhythms. In the current paper, we examined the applicability of a non-invasive fecal CORT metabolite measure to assess the circadian rhythm. We compared fecal CORT metabolite levels to circulating CORT levels, and analyzed change in the fecal circadian rhythm following an acute stressor (i.e. blood sampling by tail veil catheter). Fecal and blood samples were collected from male adolescent rats and analyzed for CORT metabolites and circulating CORT respectively. Fecal samples were collected hourly for 24 h before and after blood draw. On average, peak fecal CORT metabolite values occurred 7-9 h after the plasma CORT peak and time-matched fecal CORT values were well correlated with plasma CORT. As a result of the rapid blood draw, fecal production and CORT levels were altered the next day. These results indicate fecal CORT metabolite measures can be used to assess conditions that disrupt the circadian CORT rhythm, and provide a method to measure long-term changes in CORT production. This can benefit research that requires long-term glucocorticoid assessment (e. g. stress mechanisms underlying health). C1 [Thanos, P. K.; Michaelides, M.; Olvet, D. M.; Patel, U.] Brookhaven Natl Lab, Dept Med, Behav Neuropharmacol & Neuroimaging Lab, Upton, NY 11973 USA. [Olvet, D. M.] SUNY Stony Brook, Dept Psychol, Stony Brook, NY USA. [Thanos, P. K.; Michaelides, M.; Patel, U.; Volkow, N. D.] NIAAA, Lab Neuroimaging, NIH, Dept Hlth & Human Serv, Bethesda, MD USA. [Cavigelli, S. A.; Diep, M. N.] Penn State Univ, Dept Biobehav Hlth, University Pk, PA 16802 USA. RP Thanos, PK (reprint author), Brookhaven Natl Lab, Dept Med, Behav Neuropharmacol & Neuroimaging Lab, Bldg 490, Upton, NY 11973 USA. EM thanos@bnl.gov FU Intramural NIH HHS [Z01 AA000551-04]; NIAAA NIH HHS [AA11034, AA07574, AA07611, P50 AA007611, R01 AA011034, T32 AA007574] NR 32 TC 25 Z9 25 U1 0 U2 12 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 2009 VL 58 IS 2 BP 219 EP 228 PG 10 WC Physiology SC Physiology GA 442PM UT WOS:000265853100008 PM 18380537 ER PT J AU Cragg, GM Newman, DJ AF Cragg, G. M. Newman, D. J. TI Nature: a vital source of leads for anticancer drug development SO PHYTOCHEMISTRY REVIEWS LA English DT Article; Proceedings Paper CT International Symposium of the Phytochemical-Society-of-Europe CY SEP 23-26, 2008 CL Naples, ITALY SP Phytochem Soc Europe DE Plants; Marine organisms; Microbes; Symbionts; Multidisciplinary collaboration ID ADVANCED SOLID TUMORS; EVERY 3 WEEKS; BRYOSTATIN ANALOGS; POLYKETIDE SYNTHASE; MARINE ACTINOMYCETE; PROSTATE-CANCER; PHASE-I; TUBULIN POLYMERIZATION; BIOLOGICAL EVALUATION; THAPSIGARGIN PRODRUG AB Over 60% of the current anticancer drugs have their origin in one way or another from natural sources. Nature continues to be the most prolific source of biologically active and diverse chemotypes, and it is becoming increasingly evident that associated microbes may often be the source of biologically active compounds originally isolated from host macro-organisms. While relatively few of the actual isolated compounds advance to become clinically effective drugs in their own right, these unique molecules may serve as models for the preparation of more efficacious analogs using chemical methodology such as total or combinatorial (parallel) synthesis, or manipulation of biosynthetic pathways. In addition, conjugation of toxic natural molecules to monoclonal antibodies or polymeric carriers specifically targeted to epitopes on tumors of interest can lead to the development of efficacious targeted therapies. The essential role played by natural products in the discovery and development of effective anticancer agents, and the importance of multidisciplinary collaboration in the generation and optimization of novel molecular leads from natural product sources is reviewed. C1 [Cragg, G. M.; Newman, D. J.] US Natl Canc Inst, Nat Prod Branch, Dev Therapeut Program, Div Canc Treatment & Diag, Frederick, MD 21702 USA. RP Cragg, GM (reprint author), US Natl Canc Inst, Nat Prod Branch, Dev Therapeut Program, Div Canc Treatment & Diag, POB B, Frederick, MD 21702 USA. EM gmcragg@verizon.net NR 120 TC 76 Z9 82 U1 5 U2 35 PU SPRINGER PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 1568-7767 EI 1572-980X J9 PHYTOCHEM REV JI Phytochem. Rev. PY 2009 VL 8 IS 2 SI SI BP 313 EP 331 DI 10.1007/s11101-009-9123-y PG 19 WC Plant Sciences SC Plant Sciences GA 473VK UT WOS:000268238000002 ER PT J AU Park, CW Moon, KC Park, JS Jun, JK Romero, R Yoon, BH AF Park, Chan-Wook Moon, Kyung Chul Park, Joong Shin Jun, Jong Kwan Romero, Roberto Yoon, Bo Hyun TI The Involvement of Human Amnion in Histologic Chorioamnionitis is an Indicator that a Fetal and an Intra-Amniotic Inflammatory Response is More Likely and Severe: Clinical Implications SO PLACENTA LA English DT Article DE Amnionitis; Funisitis; Fetal inflammatory response; Intra-amnoitic inflammatory response; Chorioamnionitis ID C-REACTIVE PROTEIN; PRETERM PREMATURE RUPTURE; BLOOD-CELL COUNT; INTACT MEMBRANES; FLUID INFECTION; UMBILICAL-CORD; LABOR; LESIONS; WOMEN; INTERLEUKIN-6 AB Objective: Amnionitis (inflammation of the amnion) is the final stage of extra-placental chorioamniotic inflammation. We propose that patients with "amnionitis", rather than "chorionitis" have a more advanced form of intra-uterine inflammation/infection and, thus, would have a more intense fetal and intra-amniotic inflammatory response than those without "amnionitis". Study design: The relationship between the presence of amnionitis, and a fetal and an intra-amniotic inflammatory response was examined in 290 singleton preterm births (<= 36 weeks) with histologic chorioamnionitis. The fetal inflammatory response was determined by plasma C-reactive protein (CRP) concentrations in umbilical cord and the presence of funisitis. The intra-amniotic inflammatory response was assessed by matrix metalloproteinase-8 (MMP-8) concentration and white blood cell (WBC) count in 156 amniotic fluid (AF) samples obtained within 5 days of birth. AF was cultured for aerobic and anaerobic bacteria and genital mycoplasmas. The CRP concentration was measured with a highly sensitive immunoassay. Results: (1) Amnionitis was present in 43.1% of cases with histologic chorioamnionitis. (2) Patients with amnionitis had a significantly higher rate of funisitis and positive AF culture and a higher median umbilical cord plasma CRP, AF MMP-8 level and AF WBC count than those without amnionitis (p < 0.001 for each). (3) Among cases with amnionitis, the presence or absence of funisitis was not associated with significant differences in the median cord plasma CRP, AF MMP-8 level and AF WBC count. (4) However, the presence of amnionitis in cases with funisitis was associated with a higher median umbilical cord plasma CRP, AF MMP-8 level and AF WBC count than the absence of amnionitis in those with funisitis (p < 0.05 for each). (5) Multiple logistic regression analysis demonstrated that amnionitis was a better independent predictor of proven or suspected early-onset neonatal sepsis (odds ratio 3.8, 95% confidence interval (CI) 1.1-13.2, p < 0.05) than funisitis (odds ratio 1.8, 95% CI 0.5-6.1, not significant) after correction for the contribution of other potential confounding variables. Conclusion: The involvement of the amnion in the inflammatory process of the extraplacental membranes is associated with a more intense fetal and intra-amniotic inflammatory response than chorionitis alone. This observation has clinical implications because it allows staging of the severity of the inflammatory process and assessment of the likelihood of fetal involvement. (C) 2008 Elsevier Ltd. All rights reserved. C1 [Park, Chan-Wook; Park, Joong Shin; Jun, Jong Kwan; Yoon, Bo Hyun] Seoul Natl Univ, Coll Med, Dept Obstet & Gynecol, Seoul 110744, South Korea. [Moon, Kyung Chul] Seoul Natl Univ, Coll Med, Dept Pathol, Seoul 151, South Korea. [Romero, Roberto] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Perinatol Res Branch, Detroit, MI USA. RP Park, JS (reprint author), Seoul Natl Univ, Coll Med, Dept Obstet & Gynecol, 28 Yongon dong, Seoul 110744, South Korea. EM jsparkmd@snu.ac.kr RI Seoul National University, Pathology/B-6702-2012; Jun, Jong Kwan/D-5776-2012; Yoon, Bo Hyun/H-6344-2011; Park, Chan-Wook/J-5498-2012; Moon, Kyung Chul/J-5465-2012; OI Jun, Jong Kwan/0000-0002-0242-1736; Park, Joong Shin/0000-0002-5246-0477 FU General Research Grants (GRG); Korea Science and Engineering Foundation, Republic of Korea [R01-2006-000-10607-0]; Eunice Kennedy Shriver National Institute of Child Health and Human Development, NIH, DHHS FX This study was supported by General Research Grants (GRG), Korea Science and Engineering Foundation, Republic of Korea (R01-2006-000-10607-0) and, in part, by the Intramural Research Program of the Eunice Kennedy Shriver National Institute of Child Health and Human Development, NIH, DHHS. NR 29 TC 49 Z9 57 U1 0 U2 2 PU W B SAUNDERS CO LTD PI LONDON PA 32 JAMESTOWN RD, LONDON NW1 7BY, ENGLAND SN 0143-4004 J9 PLACENTA JI Placenta PD JAN PY 2009 VL 30 IS 1 BP 56 EP 61 DI 10.1016/j.placenta.2008.09.017 PG 6 WC Developmental Biology; Obstetrics & Gynecology; Reproductive Biology SC Developmental Biology; Obstetrics & Gynecology; Reproductive Biology GA 396EJ UT WOS:000262574700009 PM 19046766 ER PT B AU Gottesman, MM Hall, MD Liang, XJ Shen, DW AF Gottesman, Michael M. Hall, Matthew D. Liang, Xing-Jie Shen, Ding-Wu BE Bonetti, A Leone, R Muggia, FM Howell, SB TI Resistance to Cisplatin Results from Multiple Mechanisms in Cancer Cells SO PLATINUM AND OTHER HEAVY METAL COMPOUNDS IN CANCER CHEMOTHERAPY SE Cancer Drug Discovery and Development LA English DT Proceedings Paper CT 10th International Symposium on Platinum Coordination Compounds in Cancer Chemotherapy CY DEC, 2007 CL Verona, ITALY SP Mater Salutis Hosp, Dept Oncol, Azienda Sanitaria Locale 21, Veneto Reg, Univ Verona, Dept Med & Public Hlth, Sect Pharmacol DE Cisplatin; Resistance; Uptake; Reduced accumulation; Pleiotropic mechanism ID CELLULAR ACCUMULATION; MULTIDRUG-RESISTANCE; REDUCED EXPRESSION; LINES; CHEMOTHERAPY; CARBOPLATIN AB We have studied the development of resistance to cisplatin in cultured KB-3-1 human cervical adenocarcinoma (HeLa) cells and BEL-7404 human hepatoma cells. In a single-step selection, it is possible to develop a pleiotropic phenotype consisting of the following: (a) cross-resistance to other platinum compounds, arsenite, cadmium, methotrexate and nucleoside analogs; (b) corresponding reduced accumulation of these agents; (c) reduced receptor-mediated and fluid phase mediated endocytosis; (d) altered cytoskeleton, including disruption of actin microfilaments, filament structures, and microtubules; (e) a defect in membrane protein trafficking consisting of relocalization to intracellular vesicles of several transmembrane proteins Such as the ABBC1 transporter (MRP1, GS-X pump), glucose transporter (GluT1), and folate binding protein (FBP); and (f)altered mitochondrial morphology and function. We hypothesize that this pleiotropic phenotype reflects a basic cellular defense mechanism against cytotoxic materials that are not hydrophobic enough to enter the cell by simple diffusion, but have multiple other mechanisms of cell entry including piggybacking on existing receptors and endocytosis, and speculate that a relatively simple cellular switch can actuate this pleiotropic response. C1 [Gottesman, Michael M.; Hall, Matthew D.; Liang, Xing-Jie; Shen, Ding-Wu] NCI, Cell Biol Lab, NIH, Bethesda, MD 20892 USA. RP Gottesman, MM (reprint author), NCI, Cell Biol Lab, NIH, Bldg 37, Bethesda, MD 20892 USA. EM mgottesman@nih.gov NR 15 TC 5 Z9 7 U1 1 U2 5 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DR, STE 208, TOTOWA, NJ 07512-1165 USA BN 978-1-60327-458-6 J9 CANC DRUG DISC DEV JI Canc. Drug. Disc. Dev. PY 2009 BP 83 EP 88 DI 10.1007/978-1-60327-459-3_11 PG 6 WC Oncology; Pharmacology & Pharmacy SC Oncology; Pharmacology & Pharmacy GA BIV36 UT WOS:000263142100011 ER PT B AU Tay, K Gutierrez, M Giaccone, G AF Tay, Kevin Gutierrez, Martin Giaccone, Giuseppe BE Bonetti, A Leone, R Muggia, FM Howell, SB TI Platinum Compounds in Lung Cancer: Current Status SO PLATINUM AND OTHER HEAVY METAL COMPOUNDS IN CANCER CHEMOTHERAPY SE Cancer Drug Discovery and Development LA English DT Proceedings Paper CT 10th International Symposium on Platinum Coordination Compounds in Cancer Chemotherapy CY DEC, 2007 CL Verona, ITALY SP Mater Salutis Hosp, Dept Oncol, Azienda Sanitaria Locale 21, Veneto Reg, Univ Verona, Dept Med & Public Hlth, Sect Pharmacol DE Platinum compounds; Bevacizumab; Cetuximab; Excision repair cross-complementation group 1 (ERCC1); Ribonucleotide reductace MI (RRMI) ID PHASE-III TRIAL; QUALITY-OF-LIFE; CISPLATIN PLUS GEMCITABINE; RANDOMIZED CONTROLLED-TRIALS; REDUCTASE SUBUNIT M1; RIBONUCLEOTIDE REDUCTASE; SUPPORTIVE CARE; CLINICAL-TRIALS; ADJUVANT CHEMOTHERAPY; ERCC1 EXPRESSION AB Randomized clinical studies and meta-analyses of the literature have confirmed the improved survival of platinum-based chemotherapy doublets, that are considered standard therapy in patients with advanced non-small cell lung cancer (NSCLC) with a good performance status. The use of platinum compounds have also demonstrated a slight survival advantage over nonplatinum-based chemotherapy. Cisplatin remains the platinum agent of choice in the management of patients with NSCLC in both the advanced and adjuvant setting based on the results from recent meta-analyses. However, carboplatin may be offered to patients in advanced stages of the disease due to its more favorable toxicity profile. To date, four targeted agents (bevacizumab, cetuximab, erlotinib and gefitinib) have been studied in combination with platinum-based chemotherapy in the treatment of advanced NSCLC. Only bevacizumab has been shown to significantly prolong survival when added to carboplatin/paclitaxel as demonstrated in a large phase III study. However, issues of toxicity limit this treatment regimen to selected patients. The combination of bevacizumab with cisplatin and gemcitabine appears promising but is still awaiting the final results of the unpublished survival data. Preliminary studies indicate that molecular tumor markers may be able to identify tumors that are more likely to respond to chemotherapy. Excision repair cross-complementation group 1 (ERCC1) and Ribonucleotide Reductase MI (RRMI) are two such genes critical to DNA synthesis and DNA damage repair pathways that have been studied. The results from the first prospective phase III randomized trial suggest that customizing chemotherapy based on ERCC1 expression in patients with advanced NSCLC is a feasible approach. In the future, selection of patients based on pharmacogenetics may help identify patients who will optimally benefit from specific therapies. C1 [Tay, Kevin; Gutierrez, Martin; Giaccone, Giuseppe] NCI, Med Oncol Branch, NIH, Bethesda, MD USA. RP Tay, K (reprint author), NCI, Med Oncol Branch, NIH, Bethesda, MD USA. EM giacconeg@mail.nih.gov NR 58 TC 0 Z9 0 U1 0 U2 1 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DR, STE 208, TOTOWA, NJ 07512-1165 USA BN 978-1-60327-458-6 J9 CANC DRUG DISC DEV JI Canc. Drug. Disc. Dev. PY 2009 BP 231 EP 242 DI 10.1007/978-1-60327-459-3_28 PG 12 WC Oncology; Pharmacology & Pharmacy SC Oncology; Pharmacology & Pharmacy GA BIV36 UT WOS:000263142100028 ER PT J AU Pajevic, S Plenz, D AF Pajevic, Sinisa Plenz, Dietmar TI Efficient Network Reconstruction from Dynamical Cascades Identifies Small-World Topology of Neuronal Avalanches SO PLOS COMPUTATIONAL BIOLOGY LA English DT Article ID PRIMATE CEREBRAL-CORTEX; COMPLEX BRAIN NETWORKS; FUNCTIONAL CONNECTIVITY; GRANGER CAUSALITY; CORTICAL-NEURONS; IN-VITRO; INFORMATION-TRANSFER; ACTIVITY PATTERNS; NEURAL SYSTEMS; ORGANIZATION AB Cascading activity is commonly found in complex systems with directed interactions such as metabolic networks, neuronal networks, or disease spreading in social networks. Substantial insight into a system's organization can be obtained by reconstructing the underlying functional network architecture from the observed activity cascades. Here we focus on Bayesian approaches and reduce their computational demands by introducing the Iterative Bayesian (IB) and Posterior Weighted Averaging (PWA) methods. We introduce a special case of PWA, cast in nonparametric form, which we call the normalized count (NC) algorithm. NC efficiently reconstructs random and small-world functional network topologies and architectures from subcritical, critical, and supercritical cascading dynamics and yields significant improvements over commonly used correlation methods. With experimental data, NC identified a functional and structural small-world topology and its corresponding traffic in cortical networks with neuronal avalanche dynamics. C1 [Pajevic, Sinisa] Ctr Informat Technol, Math & Stat Comp Lab, Div Computat Biosci, NIH, Bethesda, MD USA. [Plenz, Dietmar] NIMH, Sect Crit Brain Dynam, Lab Syst Neurosci, NIH, Bethesda, MD 20892 USA. RP Pajevic, S (reprint author), Ctr Informat Technol, Math & Stat Comp Lab, Div Computat Biosci, NIH, Bethesda, MD USA. EM plenzd@mail.nih.gov FU National Institute of Mental Health and the Division of Computational Biosciences; Center for Information Technology, National Institutes of Health FX This work was supported by the Intramural Research Program of the National Institute of Mental Health and the Division of Computational Biosciences, Center for Information Technology, National Institutes of Health. NR 86 TC 44 Z9 46 U1 0 U2 5 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA SN 1553-734X EI 1553-7358 J9 PLOS COMPUT BIOL JI PLoS Comput. Biol. PD JAN PY 2009 VL 5 IS 1 AR e1000271 DI 10.1371/journal.pcbi.1000271 PG 20 WC Biochemical Research Methods; Mathematical & Computational Biology SC Biochemistry & Molecular Biology; Mathematical & Computational Biology GA 415HG UT WOS:000263924300005 PM 19180180 ER PT J AU Blankschien, MD Potrykus, K Grace, E Choudhary, A Vinella, D Cashel, M Herman, C AF Blankschien, Matthew D. Potrykus, Katarzyna Grace, Elicia Choudhary, Abha Vinella, Daniel Cashel, Michael Herman, Christophe TI TraR, a Homolog of a RNAP Secondary Channel Interactor, Modulates Transcription SO PLOS GENETICS LA English DT Article ID ESCHERICHIA-COLI K-12; F-PLASMID; CRYSTAL-STRUCTURE; STATIONARY-PHASE; OPPOSING ROLES; ALARMONE PPGPP; GENE-PRODUCTS; MICROCIN J25; IN-VIVO; POLYMERASE AB Recent structural and biochemical studies have identified a novel control mechanism of gene expression mediated through the secondary channel of RNA Polymerase (RNAP) during transcription initiation. Specifically, the small nucleotide ppGpp, along with DksA, a RNAP secondary channel interacting factor, modifies the kinetics of transcription initiation, resulting in, among other events, down-regulation of ribosomal RNA synthesis and up-regulation of several amino acid biosynthetic and transport genes during nutritional stress. Until now, this mode of regulation of RNAP was primarily associated with ppGpp. Here, we identify TraR, a DksA homolog that mimics ppGpp/DksA effects on RNAP. First, expression of TraR compensates for dksA transcriptional repression and activation activities in vivo. Second, mutagenesis of a conserved amino acid of TraR known to be critical for DksA function abolishes its activity, implying both structural and functional similarity to DksA. Third, unlike DksA, TraR does not require ppGpp for repression of the rrnB P1 promoter in vivo and in vitro or activation of amino acid biosynthesis/transport genes in vivo. Implications for DksA/ppGpp mechanism and roles of TraR in horizontal gene transfer and virulence are discussed. C1 [Blankschien, Matthew D.; Grace, Elicia; Choudhary, Abha; Herman, Christophe] Baylor Coll Med, Dept Mol & Human Genet, Houston, TX 77030 USA. [Potrykus, Katarzyna; Vinella, Daniel; Cashel, Michael] NICHHD, Mol Genet Lab, NIH, Bethesda, MD 20892 USA. [Grace, Elicia; Herman, Christophe] Baylor Coll Med, Dept Mol Virol & Microbiol, Houston, TX 77030 USA. RP Blankschien, MD (reprint author), Baylor Coll Med, Dept Mol & Human Genet, Houston, TX 77030 USA. EM herman@bcm.edu RI vinella, daniel/G-5504-2012 FU NIH; HFSPO [RGY0060/2006] FX This work is funded in part by the NICHD intramural program of the NIH and HFSPO grant RGY0060/2006. NR 62 TC 21 Z9 23 U1 0 U2 2 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 185 BERRY ST, STE 1300, SAN FRANCISCO, CA 94107 USA SN 1553-7390 J9 PLOS GENET JI PLoS Genet. PD JAN PY 2009 VL 5 IS 1 AR e1000345 DI 10.1371/journal.pgen.1000345 PG 13 WC Genetics & Heredity SC Genetics & Heredity GA 447VW UT WOS:000266221100027 PM 19148274 ER PT J AU Reich, D Nalls, MA Kao, WHL Akylbekova, EL Tandon, A Patterson, N Mullikin, J Hsueh, WC Cheng, CY Coresh, J Boerwinkle, E Li, M Waliszewska, A Neubauer, J Li, RL Leak, TS Ekunwe, L Files, JC Hardy, CL Zmuda, JM Taylor, HA Ziv, E Harris, TB Wilson, JG AF Reich, David Nalls, Michael A. Kao, W. H. Linda Akylbekova, Ermeg L. Tandon, Arti Patterson, Nick Mullikin, James Hsueh, Wen-Chi Cheng, Ching-Yu Coresh, Josef Boerwinkle, Eric Li, Man Waliszewska, Alicja Neubauer, Julie Li, Rongling Leak, Tennille S. Ekunwe, Lynette Files, Joe C. Hardy, Cheryl L. Zmuda, Joseph M. Taylor, Herman A. Ziv, Elad Harris, Tamara B. Wilson, James G. TI Reduced Neutrophil Count in People of African Descent Is Due To a Regulatory Variant in the Duffy Antigen Receptor for Chemokines Gene SO PLOS GENETICS LA English DT Article ID BENIGN FAMILIAL LEUKOPENIA; ETHNIC NEUTROPENIA; HUMAN GENOME; NEGATIVE INDIVIDUALS; PLASMODIUM-VIVAX; HAPLOTYPE MAP; IN-VIVO; INFECTION; BLACK; DARC AB Persistently low white blood cell count (WBC) and neutrophil count is a well-described phenomenon in persons of African ancestry, whose etiology remains unknown. We recently used admixture mapping to identify an approximately 1-megabase region on chromosome 1, where ancestry status (African or European) almost entirely accounted for the difference in WBC between African Americans and European Americans. To identify the specific genetic change responsible for this association, we analyzed genotype and phenotype data from 6,005 African Americans from the Jackson Heart Study (JHS), the Health, Aging and Body Composition (Health ABC) Study, and the Atherosclerosis Risk in Communities (ARIC) Study. We demonstrate that the causal variant must be at least 91% different in frequency between West Africans and European Americans. An excellent candidate is the Duffy Null polymorphism (SNP rs2814778 at chromosome 1q23.2), which is the only polymorphism in the region known to be so differentiated in frequency and is already known to protect against Plasmodium vivax malaria. We confirm that rs2814778 is predictive of WBC and neutrophil count in African Americans above beyond the previously described admixture association (P = 3.8x10(-5)), establishing a novel phenotype for this genetic variant. C1 [Reich, David; Tandon, Arti] Harvard Univ, Sch Med, Dept Genet, Boston, MA 02115 USA. [Reich, David; Tandon, Arti; Patterson, Nick; Waliszewska, Alicja; Neubauer, Julie] Broad Inst Harvard, Cambridge, MA USA. [Reich, David; Tandon, Arti; Patterson, Nick; Waliszewska, Alicja; Neubauer, Julie] MIT, Cambridge, MA 02139 USA. [Nalls, Michael A.] NIA, Neurogenet Lab, Intramural Res Program, Bethesda, MD 20892 USA. [Nalls, Michael A.; Harris, Tamara B.] NIA, Lab Epidemiol Demog & Biometry, Intramural Res Program, Bethesda, MD 20892 USA. [Kao, W. H. Linda; Cheng, Ching-Yu; Coresh, Josef; Li, Man] Johns Hopkins Bloomberg Sch Publ Hlth, Dept Epidemiol, Baltimore, MD USA. [Akylbekova, Ermeg L.; Ekunwe, Lynette] Jackson State Univ, Jackson Heart Study Anal Grp, Jackson, MS USA. [Mullikin, James] NHGRI, Comparat Genom Unit, Genome Technol Branch, Rockville, MD USA. [Hsueh, Wen-Chi] Univ Calif San Francisco, Dept Epidemiol & Biostat, Inst Human Genet, Div Med Genet,Dept Med, San Francisco, CA 94143 USA. [Cheng, Ching-Yu] NHGRI, Inherited Dis Res Branch, Baltimore, MD USA. [Boerwinkle, Eric] Univ Texas Hlth Sci Ctr Houston, Ctr Human Genet, Houston, TX USA. [Waliszewska, Alicja] Brigham & Womens Hosp, Ctr Neurol Dis, Lab Mol Immunol, Boston, MA 02115 USA. [Li, Rongling] Univ Tennessee, Hlth Sci Ctr, Dept Prevent Med, Ctr Genom & Bioinformat, Memphis, TN USA. [Leak, Tennille S.; Zmuda, Joseph M.] Univ Pittsburgh, Grad Sch Publ Hlth, Dept Epidemiol, Pittsburgh, PA USA. [Files, Joe C.; Hardy, Cheryl L.] Univ Mississippi, Med Ctr, Dept Med, Div Hematol, Jackson, MS 39216 USA. [Taylor, Herman A.] Tougaloo Coll, Jackson, MS USA. [Ziv, Elad] Univ Calif San Francisco, Dept Med, Div Gen Internal Med, San Francisco, CA 94143 USA. [Ziv, Elad] Univ Calif San Francisco, Helen Diller Family Comprehens Canc Ctr, San Francisco, CA 94143 USA. [Wilson, James G.] VA Med Ctr, Jackson, MS USA. RP Reich, D (reprint author), Harvard Univ, Sch Med, Dept Genet, Boston, MA 02115 USA. EM reich@genetics.med.harvard.edu; James.Wilson3@va.gov RI Cheng, Ching-Yu/K-7017-2013; Ziv, Elad/L-5396-2014 OI Cheng, Ching-Yu/0000-0003-0655-885X; FU National Heart, Lung, and Blood Institute [R01-HL-084107, N01-HC-95170, N01-HC-95171, N01-HC-95172, N01-HC55015, N01-HC-55016, N01-HC-55018, N01-HC-55019, N01-HC-55020, N01-HC-55021, N01-HC-55022]; National Center on Minority Health and Health Disparities; National Institute on Aging [N01-AG-6-2101, N01-AG-6-2103, N01-AG-6-2106]; National Center for Research Resources to the Broad Institute of Harvard and MIT [U54 RR020278]; Burroughs Wellcome Career Development; [R21DK073482]; [K01DK067207]; [U01-HG004168] FX Research support for JHS was provided by R01-HL-084107 (JGW) from the National Heart, Lung, and Blood Institute and contracts N01-HC-95170, N01-HC-95171, and N01-HC-95172 from the National Heart, Lung, and Blood Institute and the National Center on Minority Health and Health Disparities. Research support for Health ABC was provided by the Intramural Research Program of the National Institute on Aging, and contracts N01-AG-6-2101, N01-AG-6-2103, and N01-AG-6-2106. The Atherosclerosis Risk in Communities Study is a collaborative study supported by National Heart, Lung, and Blood Institute contracts N01-HC55015, N01-HC-55016, N01-HC-55018, N01-HC-55019, N01-HC-55020, N01-HC-55021, and N01-HC-55022. Support for the ARIC admixture mapping studies was provided by R21DK073482 and K01DK067207 (WHLK). Genotyping for both the JHS and Health ABC was supported by grant U54 RR020278 from the National Center for Research Resources to the Broad Institute of Harvard and MIT; a subsidy from this grant covered half the cost of Health ABC genotyping. DR was supported by a Burroughs Wellcome Career Development Award in the Biomedical Sciences, and methodological and statistical analysis was supported by grant U01-HG004168. NR 48 TC 127 Z9 129 U1 2 U2 5 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 185 BERRY ST, STE 1300, SAN FRANCISCO, CA 94107 USA SN 1553-7390 J9 PLOS GENET JI PLoS Genet. PD JAN PY 2009 VL 5 IS 1 AR e1000360 DI 10.1371/journal.pgen.1000360 PG 14 WC Genetics & Heredity SC Genetics & Heredity GA 447VW UT WOS:000266221100042 PM 19180233 ER PT J AU Tanaka, T Shen, J Abecasis, GR Kisialiou, A Ordovas, JM Guralnik, JM Singleton, A Bandinelli, S Cherubini, A Arnett, D Tsai, MY Ferrucci, L AF Tanaka, Toshiko Shen, Jian Abecasis, Goncalo R. Kisialiou, Aliaksei Ordovas, Jose M. Guralnik, Jack M. Singleton, Andrew Bandinelli, Stefania Cherubini, Antonio Arnett, Donna Tsai, Michael Y. Ferrucci, Luigi TI Genome-Wide Association Study of Plasma Polyunsaturated Fatty Acids in the InCHIANTI Study SO PLOS GENETICS LA English DT Article ID PROLIFERATOR-ACTIVATED RECEPTOR; ALPHA-LINOLENIC ACID; CORONARY-HEART-DISEASE; DIETARY-INTAKE; FISH CONSUMPTION; GENETIC-VARIANTS; RISK; EXPRESSION; OMEGA-3-FATTY-ACIDS; ATHEROSCLEROSIS AB Polyunsaturated fatty acids (PUFA) have a role in many physiological processes, including energy production, modulation of inflammation, and maintenance of cell membrane integrity. High plasma PUFA concentrations have been shown to have beneficial effects on cardiovascular disease and mortality. To identify genetic contributors of plasma PUFA concentrations, we conducted a genome-wide association study of plasma levels of six omega-3 and omega-6 fatty acids in 1,075 participants in the InCHIANTI study on aging. The strongest evidence for association was observed in a region of chromosome 11 that encodes three fatty acid desaturases (FADS1, FADS2, FADS3). The SNP with the most significant association was rs174537 near FADS1 in the analysis of arachidonic acid (AA; p = 5.95x10(-46)). Minor allele homozygotes had lower AA compared to the major allele homozygotes and rs174537 accounted for 18.6% of the additive variance in AA concentrations. This SNP was also associated with levels of eicosadienoic acid (EDA; p = 6.78x10(-9)) and eicosapentanoic acid (EPA; p = 1.07x10(-14)). Participants carrying the allele associated with higher AA, EDA, and EPA also had higher low-density lipoprotein (LDL-C) and total cholesterol levels. Outside the FADS gene cluster, the strongest region of association mapped to chromosome 6 in the region encoding an elongase of very long fatty acids 2 (ELOVL2). In this region, association was observed with EPA (rs953413; p = 1.1x10(-6)). The effects of rs174537 were confirmed in an independent sample of 1,076 subjects participating in the GOLDN study. The ELOVL2 SNP was associated with docosapentanoic and DHA but not with EPA in GOLDN. These findings show that polymorphisms of genes encoding enzymes in the metabolism of PUFA contribute to plasma concentrations of fatty acids. C1 [Tanaka, Toshiko; Ferrucci, Luigi] Medstar Res Inst, Baltimore, MD USA. [Tanaka, Toshiko; Ferrucci, Luigi] NIA, Clin Res Branch, Baltimore, MD 21224 USA. [Shen, Jian; Ordovas, Jose M.] Tufts Univ, Human Nutr Res Ctr Aging, JM USDA, Lab Nutr Genom, Boston, MA 02111 USA. [Abecasis, Goncalo R.] Univ Michigan, Dept Biostat, Ctr Stat Genet, Ann Arbor, MI 48109 USA. [Kisialiou, Aliaksei; Bandinelli, Stefania; Ferrucci, Luigi] ASF, Geriatr Rehabil Unit, Florence, Italy. [Guralnik, Jack M.] NIA, Lab Epidemiol Demog & Biometry, Bethesda, MD 20892 USA. [Singleton, Andrew] NIA, Neurogenet Lab, Bethesda, MD 20892 USA. [Cherubini, Antonio] Univ Perugia, Inst Gerontol & Geriatr, Dept Clin & Expt Med, I-06100 Perugia, Italy. [Arnett, Donna] Univ Alabama, Sch Publ Hlth, Dept Epidemiol, Birmingham, AL 35294 USA. [Arnett, Donna] Univ Alabama, Clin Nutr Res Ctr, Birmingham, AL USA. [Tsai, Michael Y.] Univ Minnesota, Lab Med & Pathol, Minneapolis, MN USA. RP Tanaka, T (reprint author), Medstar Res Inst, Baltimore, MD USA. EM tanakato@mail.nih.gov RI Singleton, Andrew/C-3010-2009; Abecasis, Goncalo/B-7840-2010; Kisialiou, Aliaksei/J-8771-2016; OI Kisialiou, Aliaksei/0000-0001-7287-9454; Abecasis, Goncalo/0000-0003-1509-1825; Cherubini, Antonio/0000-0003-0261-9897; Ordovas, Jose/0000-0002-7581-5680 FU R&D contract with MedStar Research Institute; NIH; National Institute on Aging; National Heart, Lung, and Blood Institute [U01 HL72524, HL-54776, DK075030]; US Department of Agriculture Research Service [53-K06-5-10, 58-1950-9-001] FX This study was supported in part by the R&D contract with MedStar Research Institute, the Intramural Research Program of the NIH, National Institute on Aging and by National Heart, Lung, and Blood Institute Grant U01 HL72524, Genetic and Environmental Determinants of Triglycerides; Grants HL-54776 and DK075030, and by contracts 53-K06-5-10 and 58-1950-9-001 from the US Department of Agriculture Research Service. NR 55 TC 187 Z9 191 U1 0 U2 18 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 185 BERRY ST, STE 1300, SAN FRANCISCO, CA 94107 USA SN 1553-7390 J9 PLOS GENET JI PLoS Genet. PD JAN PY 2009 VL 5 IS 1 AR e1000338 DI 10.1371/journal.pgen.1000338 PG 8 WC Genetics & Heredity SC Genetics & Heredity GA 447VW UT WOS:000266221100020 PM 19148276 ER PT J AU Botosso, VF Zanotto, PMDA Ueda, M Arruda, E Gilio, AE Vieira, SE Stewien, KE Peret, TCT Jamal, LF Pardini, MIDMC Pinho, JRR Massad, E Sant'Anna, OA Holmes, EC Durigon, EL AF Botosso, Viviane F. Zanotto, Paolo M. de A. Ueda, Mirthes Arruda, Eurico Gilio, Alfredo E. Vieira, Sandra E. Stewien, Klaus E. Peret, Teresa C. T. Jamal, Leda F. Pardini, Maria I. de M. C. Pinho, Joao R. R. Massad, Eduardo Sant'Anna, Osvaldo A. Holmes, Eddie C. Durigon, Edison L. CA VGDN Consortium TI Positive Selection Results in Frequent Reversible Amino Acid Replacements in the G Protein Gene of Human Respiratory Syncytial Virus SO PLOS PATHOGENS LA English DT Article ID ATTACHMENT G-GLYCOPROTEIN; CARBOHYDRATE SIDE-CHAINS; SUBGROUP-A; MOLECULAR EPIDEMIOLOGY; GROUP-B; CIRCULATION PATTERNS; SOUTH-AFRICA; MONOCLONAL-ANTIBODIES; EVOLUTIONARY PATTERN; CONSECUTIVE SEASONS AB Human respiratory syncytial virus (HRSV) is the major cause of lower respiratory tract infections in children under 5 years of age and the elderly, causing annual disease outbreaks during the fall and winter. Multiple lineages of the HRSVA and HRSVB serotypes co-circulate within a single outbreak and display a strongly temporal pattern of genetic variation, with a replacement of dominant genotypes occurring during consecutive years. In the present study we utilized phylogenetic methods to detect and map sites subject to adaptive evolution in the G protein of HRSVA and HRSVB. A total of 29 and 23 amino acid sites were found to be putatively positively selected in HRSVA and HRSVB, respectively. Several of these sites defined genotypes and lineages within genotypes in both groups, and correlated well with epitopes previously described in group A. Remarkably, 18 of these positively selected tended to revert in time to a previous codon state, producing a "flipflop'' phylogenetic pattern. Such frequent evolutionary reversals in HRSV are indicative of a combination of frequent positive selection, reflecting the changing immune status of the human population, and a limited repertoire of functionally viable amino acids at specific amino acid sites. C1 [Botosso, Viviane F.; Sant'Anna, Osvaldo A.] Butantan Inst, Virol Branch, Sao Paulo, Brazil. [Zanotto, Paolo M. de A.; Stewien, Klaus E.] Univ Sao Paulo, Dept Microbiol, Inst Biomed Sci, Lab Mol Evolut & Bioinformat, Sao Paulo, Brazil. [Ueda, Mirthes] Adolfo Lutz Inst, Div Med Biol, Sao Paulo, Brazil. [Arruda, Eurico] Univ Sao Paulo, Dept Cell Biol, Fac Med Ribeirao Preto, Sao Paulo, Brazil. [Gilio, Alfredo E.; Vieira, Sandra E.] Univ Sao Paulo, Univ Hosp, Div Pediat, Sao Paulo, Brazil. [Peret, Teresa C. T.] Ctr Dis Control & Prevent, Coordinating Ctr Infect Dis, Natl Ctr Immunizat & Resp Dis, Gastroenteritis & Resp Viruses Lab Branch,Div Vir, Atlanta, GA USA. [Jamal, Leda F.] STD AIDS Reference & Training Ctr, Sao Paulo, Brazil. [Pardini, Maria I. de M. C.] State Univ Sao Paulo, Sao Paulo, Brazil. [Pinho, Joao R. R.] Univ Sao Paulo, Inst Trop Med, Sao Paulo, Brazil. [Massad, Eduardo] Univ Sao Paulo, Sch Med, Dept Legal Med, Sao Paulo, Brazil. [Holmes, Eddie C.] Penn State Univ, Dept Biol, Ctr Infect Dis Dynam, Mueller Lab, University Pk, PA 16802 USA. [Holmes, Eddie C.] NIH, Fogarty Int Ctr, Bethesda, MD 20892 USA. [Durigon, Edison L.] Univ Sao Paulo, Dept Microbiol, Inst Biomed Sci, Lab Clin Virol, Sao Paulo, Brazil. RP Botosso, VF (reprint author), Butantan Inst, Virol Branch, Sao Paulo, Brazil. EM pzanotto@usp.br RI Botosso, Viviane/I-5591-2014; Schvartsman, Claudio/M-8706-2015; Moraes, Claudia/K-4708-2016; Gilio, Alfredo/A-8819-2010; Massad, Eduardo/H-6143-2011; Arruda, Eurico/E-4101-2012; vieira, sandra/I-9456-2012; Massad, Eduardo/B-1169-2012; Toxinas, Inct/I-1933-2013; Pinho, Joao/G-2850-2012; Proenca-Modena, Jose/C-8231-2014; Gilio, Alfredo/J-4229-2014 OI Durigon, Edison/0000-0003-4898-6553; Grisi Candeias, Joao Manuel/0000-0003-1515-702X; Holmes, Edward/0000-0001-9596-3552; Botosso, Viviane/0000-0002-7876-3687; Schvartsman, Claudio/0000-0001-5695-9331; Moraes, Claudia/0000-0001-6782-4790; vieira, sandra/0000-0001-5100-8713; Massad, Eduardo/0000-0002-7200-2916; Pinho, Joao/0000-0003-3999-0489; FU FAPESP [00/04205-6]; CNPq, Brazil FX This project was made possible by the VGDN program funded by FAPESP project #00/04205-6 and by CNPq, Brazil. NR 55 TC 62 Z9 64 U1 1 U2 10 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 185 BERRY ST, STE 1300, SAN FRANCISCO, CA 94107 USA SN 1553-7366 J9 PLOS PATHOG JI PLoS Pathog. PD JAN PY 2009 VL 5 IS 1 AR e1000254 DI 10.1371/journal.ppat.1000254 PG 11 WC Microbiology; Parasitology; Virology SC Microbiology; Parasitology; Virology GA 415IP UT WOS:000263927800031 PM 19119418 ER PT J AU Jia, B Ng, SK DeGottardi, MQ Piatak, M Yuste, E Carville, A Mansfield, KG Li, WJ Richardson, BA Lifson, JD Evans, DT AF Jia, Bin Ng, Sharon K. DeGottardi, M. Quinn Piatak, Michael, Jr. Yuste, Eloisa Carville, Angela Mansfield, Keith G. Li, Wenjun Richardson, Barbra A. Lifson, Jeffrey D. Evans, David T. TI Immunization with Single-Cycle SIV Significantly Reduces Viral Loads After an Intravenous Challenge with SIV(mac)239 SO PLOS PATHOGENS LA English DT Article ID SIMIAN-IMMUNODEFICIENCY-VIRUS; MAJOR HISTOCOMPATIBILITY COMPLEX; LIVE-ATTENUATED SIV; CD4(+) T-CELLS; VESICULAR STOMATITIS-VIRUS; RHESUS MACAQUES; AIDS VACCINE; CLASS-I; IMMUNE-RESPONSES; NEUTRALIZING ANTIBODIES AB Strains of simian immunodeficiency virus (SIV) that are limited to a single cycle of infection were evaluated for the ability to elicit protective immunity against wild-type SIV(mac)239 infection of rhesus macaques by two different vaccine regimens. Six animals were inoculated at 8-week intervals with 6 identical doses consisting of a mixture of three different envelope variants of single-cycle SIV (scSIV). Six additional animals were primed with a mixture of cytoplasmic domain-truncated envelope variants of scSIV and boosted with two doses of vesicular stomatitis virus glycoprotein (VSV G) trans-complemented scSIV. While both regimens elicited detectable virus-specific T cell responses, SIV-specific T cell frequencies were more than 10-fold higher after boosting with VSV G trans-complemented scSIV (VSV G scSIV). Broad T cell recognition of multiple viral antigens and Gag-specific CD4(+) T cell responses were also observed after boosting with VSV G scSIV. With the exception of a single animal in the repeated immunization group, all of the animals became infected following an intravenous challenge with SIV(mac)239. However, significantly lower viral loads and higher memory CD4(+) T cell counts were observed in both immunized groups relative to an unvaccinated control group. Indeed, both scSIV immunization regimens resulted in containment of SIV(mac)239 replication after challenge that was as good as, if not better than, what has been achieved by other non-persisting vaccine vectors that have been evaluated in this challenge model. Nevertheless, the extent of protection afforded by scSIV was not as good as typically conferred by persistent infection with live, attenuated SIV. These observations have potentially important implications to the design of an effective AIDS vaccine, since they suggest that ongoing stimulation of virus-specific immune responses may be essential to achieving the degree of protection afforded by live, attenuated SIV. C1 [Jia, Bin; Ng, Sharon K.; DeGottardi, M. Quinn; Yuste, Eloisa; Evans, David T.] Harvard Univ, New England Reg Primate Res Ctr, Sch Med, Dept Microbiol & Mol Genet, Southborough, MA 01772 USA. [Piatak, Michael, Jr.; Lifson, Jeffrey D.] SAIC Frederick Inc, Natl Canc Inst, AIDS & Canc Virus Program, Frederick, MD USA. [Carville, Angela; Mansfield, Keith G.] Harvard Univ, New England Reg Primate Res Ctr, Sch Med, Dept Pathol, Southborough, MA 01772 USA. [Li, Wenjun] Univ Massachusetts, Sch Med, Biostat Res Grp, Div Prevent & Behav Med, Worcester, MA USA. [Richardson, Barbra A.] Univ Washington, Dept Biostat, Seattle, WA 98195 USA. RP Jia, B (reprint author), Harvard Univ, New England Reg Primate Res Ctr, Sch Med, Dept Microbiol & Mol Genet, Southborough, MA 01772 USA. EM devans@hms.harvard.edu FU Public Health Service [AI63993, AI52751, AI71306]; National Institutes of Health; Elizabeth Glaser Pediatric AIDS Foundation FX This work was supported by Public Health Service grants AI63993, AI52751, and AI71306 from the National Institutes of Health. DTE is an Elizabeth Glaser Scientist supported by the Elizabeth Glaser Pediatric AIDS Foundation. NR 84 TC 28 Z9 28 U1 0 U2 2 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 185 BERRY ST, STE 1300, SAN FRANCISCO, CA 94107 USA SN 1553-7366 J9 PLOS PATHOG JI PLoS Pathog. PD JAN PY 2009 VL 5 IS 1 AR e1000272 DI 10.1371/journal.ppat.1000272 PG 19 WC Microbiology; Parasitology; Virology SC Microbiology; Parasitology; Virology GA 415IP UT WOS:000263927800011 PM 19165322 ER PT J AU Ninio, S Celli, J Roy, CR AF Ninio, Shira Celli, Jean Roy, Craig R. TI A Legionella pneumophila Effector Protein Encoded in a Region of Genomic Plasticity Binds to Dot/Icm-Modified Vacuoles SO PLOS PATHOGENS LA English DT Article ID NUCLEOTIDE-EXCHANGE FACTOR; IV SECRETION SYSTEM; LEGIONNAIRES-DISEASE; ENDOPLASMIC-RETICULUM; INTRACELLULAR GROWTH; HUMAN-MONOCYTES; TRANSLOCATED SUBSTRATE; HOST-CELLS; BACTERIUM; IDENTIFICATION AB Legionella pneumophila is an opportunistic pathogen that can cause a severe pneumonia called Legionnaires' disease. In the environment, L. pneumophila is found in fresh water reservoirs in a large spectrum of environmental conditions, where the bacteria are able to replicate within a variety of protozoan hosts. To survive within eukaryotic cells, L. pneumophila require a type IV secretion system, designated Dot/Icm, that delivers bacterial effector proteins into the host cell cytoplasm. In recent years, a number of Dot/Icm substrate proteins have been identified; however, the function of most of these proteins remains unknown, and it is unclear why the bacterium maintains such a large repertoire of effectors to promote its survival. Here we investigate a region of the L. pneumophila chromosome that displays a high degree of plasticity among four sequenced L. pneumophila strains. Analysis of GC content suggests that several genes encoded in this region were acquired through horizontal gene transfer. Protein translocation studies establish that this region of genomic plasticity encodes for multiple Dot/Icm effectors. Ectopic expression studies in mammalian cells indicate that one of these substrates, a protein called PieA, has unique effector activities. PieA is an effector that can alter lysosome morphology and associates specifically with vacuoles that support L. pneumophila replication. It was determined that the association of PieA with vacuoles containing L. pneumophila requires modifications to the vacuole mediated by other Dot/Icm effectors. Thus, the localization properties of PieA reveal that the Dot/Icm system has the ability to spatially and temporally control the association of an effector with vacuoles containing L. pneumophila through activities mediated by other effector proteins. C1 [Ninio, Shira; Roy, Craig R.] Yale Univ, Sch Med, Boyer Ctr Mol Med, Sect Microbial Pathogenesis, New Haven, CT 06520 USA. [Celli, Jean] NIAID, Rocky Mt Labs, Intracellular Parasites Lab, NIH, Hamilton, MT 59840 USA. RP Ninio, S (reprint author), Yale Univ, Sch Med, Boyer Ctr Mol Med, Sect Microbial Pathogenesis, New Haven, CT 06520 USA. EM Craig.roy@yale.edu OI Roy, Craig/0000-0003-4490-440X FU NIH [2R01AI041699-12]; The Human Frontiers Science Program; Intramural Research Program of the National Institutes of Health; National Institute of Allergy and Infectious Diseases FX This work was supported by NIH Grant 2R01AI041699-12 (C. R. R.), by The Human Frontiers Science Program (S. N.), and by the Intramural Research Program of the National Institutes of Health, National Institute of Allergy and Infectious Diseases (J.C.). NR 58 TC 36 Z9 36 U1 1 U2 4 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA SN 1553-7366 EI 1553-7374 J9 PLOS PATHOG JI PLoS Pathog. PD JAN PY 2009 VL 5 IS 1 AR e1000278 DI 10.1371/journal.ppat.1000278 PG 13 WC Microbiology; Parasitology; Virology SC Microbiology; Parasitology; Virology GA 415IP UT WOS:000263927800016 PM 19165328 ER PT J AU Srinivasan, P Coppens, I Jacobs-Lorena, M AF Srinivasan, Prakash Coppens, Isabelle Jacobs-Lorena, Marcelo TI Distinct Roles of Plasmodium Rhomboid 1 in Parasite Development and Malaria Pathogenesis SO PLOS PATHOGENS LA English DT Article ID APICAL MEMBRANE ANTIGEN-1; HOST-CELL INVASION; ERYTHROCYTE INVASION; GLIDING MOTILITY; LIFE-CYCLE; SEXUAL DEVELOPMENT; FALCIPARUM; PROTEIN; SURFACE; MEROZOITES AB Invasion of host cells by the malaria parasite involves recognition and interaction with cell-surface receptors. A wide variety of parasite surface proteins participate in this process, most of which are specific to the parasite's particular invasive form. Upon entry, the parasite has to dissociate itself from the host-cell receptors. One mechanism by which it does so is by shedding its surface ligands using specific enzymes. Rhomboid belongs to a family of serine proteases that cleave cell-surface proteins within their transmembrane domains. Here we identify and partially characterize a Plasmodium berghei rhomboid protease (PbROM1) that plays distinct roles during parasite development. PbROM1 localizes to the surface of sporozoites after salivary gland invasion. In blood stage merozoites, PbROM1 localizes to the apical end where proteins involved in invasion are also present. Our genetic analysis suggests that PbROM1 functions in the invasive stages of parasite development. Whereas wild-type P. berghei is lethal to mice, animals infected with PbROM1 null mutants clear the parasites efficiently and develop long-lasting protective immunity. The results indicate that P. berghei Rhomboid 1 plays a nonessential but important role during parasite development and identify rhomboid proteases as potential targets for disease control. C1 Johns Hopkins Sch Publ Hlth, Malaria Res Inst, Baltimore, MD USA. Johns Hopkins Sch Publ Hlth, Dept Mol Microbiol & Immunol, Baltimore, MD USA. RP Srinivasan, P (reprint author), NIAID, Malaria Cell Biol Sect, Lab Malaria & Vector Res, NIH, Rockville, MD USA. EM srinivasanp@niaid.nih.gov FU Johns Hopkins Malaria Research Institute; The Bloomberg Family Foundation [R01 AI 1031478]; National Institute of Allergy and Infectious Diseases FX This work was supported by Johns Hopkins Malaria Research Institute, The Bloomberg Family Foundation, and grant R01 AI 1031478 from the National Institute of Allergy and Infectious Diseases. NR 51 TC 22 Z9 22 U1 0 U2 1 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 185 BERRY ST, STE 1300, SAN FRANCISCO, CA 94107 USA SN 1553-7366 J9 PLOS PATHOG JI PLoS Pathog. PD JAN PY 2009 VL 5 IS 1 AR e1000262 DI 10.1371/journal.ppat.1000262 PG 10 WC Microbiology; Parasitology; Virology SC Microbiology; Parasitology; Virology GA 415IP UT WOS:000263927800017 PM 19148267 ER PT J AU Sandel, ME Wang, H Terdiman, J Hoffman, JM Ciol, MA Sidney, S Quesenberry, C Lu, Q Chan, L AF Sandel, M. Elizabeth Wang, Hua Terdiman, Joseph Hoffman, Jeanne M. Ciol, Marcia A. Sidney, Steven Quesenberry, Charles Lu, Qi Chan, Leighton TI Disparities in Stroke Rehabilitation: Results of a Study in an Integrated Health System in Northern California SO PM&R LA English DT Article AB Objective: To determine whether there are disparities in postacute stroke rehabilitation based on type of stroke, race/ethnicity, sex/gender, age, socioeconomic status, geographic region, or service area referral patterns in a large integrated health system with multiple levels of care. Design: Cohort study tracking rehabilitation services for 365 days after acute hospitalization for a first stroke. Setting: The Northern California Kaiser Permanente Health System (approximately 3.3 million membership population) Participants: A total of 11,119 patients hospitalized for acute stroke from 1996 to 2003. The cohort includes patients discharged from acute care after a stroke. Postacute care rehabilitation services were evaluated according to the level of care ever-received within the 365 days after discharge from acute care, including inpatient rehabilitation hospital (IRH), skilled nursing facility (SNF), home health and outpatient, or no rehabilitation services. Interventions: Not applicable. Main Outcome Measure: Service delivery. Results: Patients discharged to an IRH had longer lengths of stay in acute care. Patients with hemorrhagic stroke were less likely to be treated in an I RH. Patients whose highest level of rehabilitation was SNF were older and more likely to be women. After adjusting for age and other covariates, women were less likely to go to an IRH than men. Asian and black patients were more likely than white patients to be treated in an IRH or SNF. Also more likely to go to an IRH were patients from higher socioeconomic groups, from urban areas, and from geographic areas close to the regional rehabilitation hospital. Conclusions: These results suggest variation in care delivery and extent of postacute care based on differences in patient demographics and geographic factors. Results also varied over time. Some minority populations in this cohort appeared to be more likely to receive IRH care, possibly because of disease severity, family support systems, cultural factors, or differences in referral patterns. C1 [Sandel, M. Elizabeth] Kaiser Fdn Rehabil Ctr, Napa Solano Serv Area, Vallejo, CA 94589 USA. [Terdiman, Joseph; Sidney, Steven; Quesenberry, Charles; Lu, Qi] Kaiser Permanente, Div Res, Oakland, CA USA. [Hoffman, Jeanne M.; Ciol, Marcia A.] Univ Washington, Seattle, WA 98195 USA. [Chan, Leighton] NIH, Bethesda, MD 20892 USA. RP Sandel, ME (reprint author), Kaiser Fdn Rehabil Ctr, Napa Solano Serv Area, 975 Sereno Dr, Vallejo, CA 94589 USA. EM elizabeth.sandel@kp.org FU Centers for Disease Control and Prevention FX This study was supported with funding from the Centers for Disease Control and Prevention. Additional resources were provided by the Intramural Research Program (Clinical Center) of the National Institutes of Health, the Centers for Medicare and Medicaid Services, and Kaiser Permanente. NR 34 TC 20 Z9 20 U1 0 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1934-1482 J9 PM&R JI PM&R PD JAN PY 2009 VL 1 IS 1 BP 29 EP 40 DI 10.1016/j.pmrj.2008.10.012 PG 12 WC Rehabilitation; Sport Sciences SC Rehabilitation; Sport Sciences GA V24LD UT WOS:000208411000006 PM 19627870 ER PT J AU Hardwick, JP Osei-Hyiaman, D Wiland, H Abdelmegeed, MA Song, BJ AF Hardwick, James P. Osei-Hyiaman, Douglas Wiland, Homer Abdelmegeed, Mohamed A. Song, Byoung-Joon TI PPAR/RXR Regulation of Fatty Acid Metabolism and Fatty Acid omega-Hydroxylase (CYP4) Isozymes: Implications for Prevention of Lipotoxicity in Fatty Liver Disease SO PPAR RESEARCH LA English DT Review ID ACTIVATED-RECEPTOR-ALPHA; TRIGLYCERIDE TRANSFER PROTEIN; HEPATIC CYTOCHROME-P450 2E1; ELEMENT-BINDING PROTEIN-1C; TYPE-2 DIABETES-MELLITUS; DIET-INDUCED OBESITY; ACYL-COA OXIDASE; VERY-LONG-CHAIN; INSULIN-RESISTANCE; NONALCOHOLIC STEATOHEPATITIS AB Fatty liver disease is a common lipid metabolism disorder influenced by the combination of individual genetic makeup, drug exposure, and life-style choices that are frequently associated with metabolic syndrome, which encompasses obesity, dyslipidemia, hypertension, hypertriglyceridemia, and insulin resistant diabetes. Common to obesity related dyslipidemia is the excessive storage of hepatic fatty acids (steatosis), due to a decrease in mitochondria beta-oxidation with an increase in both peroxisomal beta-oxidation, and microsomal.-oxidation of fatty acids through peroxisome proliferator activated receptors (PPARs). How steatosis increases PPAR alpha activated gene expression of fatty acid transport proteins, peroxisomal and mitochondrial fatty acid beta-oxidation and omega-oxidation of fatty acids genes regardless of whether dietary fatty acids are polyunsaturated (PUFA), monounsaturated (MUFA), or saturated (SFA) may be determined by the interplay of PPARs and HNF4 alpha with the fatty acid transport proteins L-FABP and ACBP. In hepatic steatosis and steatohepatitis, the omega-oxidation cytochrome P450 CYP4A gene expression is increased even with reduced hepatic levels of PPARa. Although numerous studies have suggested the role ethanol-inducible CYP2E1 in contributing to increased oxidative stress, Cyp2e1-null mice still develop steatohepatitis with a dramatic increase in CYP4A gene expression. This strongly implies that CYP4A fatty acid.-hydroxylase P450s may play an important role in the development of steatohepatitis. In this review and tutorial, we briefly describe how fatty acids are partitioned by fatty acid transport proteins to either anabolic or catabolic pathways regulated by PPARs, and we explore how medium-chain fatty acid (MCFA) CYP4A and long-chain fatty acid (LCFA) CYP4F omega-hydroxylase genes are regulated in fatty liver. We finally propose a hypothesis that increased CYP4A expression with a decrease in CYP4F genes may promote the progression of steatosis to steatohepatitis. Copyright (C) 2009 James P. Hardwick et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. C1 [Hardwick, James P.; Wiland, Homer] NE OH Univ Coll Med & Pharm NEOUCOM NEOUCOP, Dept Integrat Med Sci, Rootstown, OH 44272 USA. [Osei-Hyiaman, Douglas] NIAAA, Lab Physiol Studies, NIH, Bethesda, MD 20892 USA. [Osei-Hyiaman, Douglas] Nippon Boehringer Ingelheim Co Ltd, CardioMetab Dis Res Grp, Dept Mol & Cellular Biol, Kobe Pharma Res Inst,Chuo Ku, Kobe, Hyogo 6500047, Japan. [Abdelmegeed, Mohamed A.; Song, Byoung-Joon] NIAAA, Lab Membrane Biochem & Biophys, NIH, Bethesda, MD 20892 USA. RP Hardwick, JP (reprint author), NE OH Univ Coll Med & Pharm NEOUCOM NEOUCOP, Dept Integrat Med Sci, 4209 State Route 44, Rootstown, OH 44272 USA. EM jph@neoucom.edu NR 152 TC 43 Z9 43 U1 1 U2 14 PU HINDAWI PUBLISHING CORPORATION PI NEW YORK PA 410 PARK AVENUE, 15TH FLOOR, #287 PMB, NEW YORK, NY 10022 USA SN 1687-4757 J9 PPAR RES JI PPAR Res. PY 2009 AR 952734 DI 10.1155/2009/952734 PG 20 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 670JV UT WOS:000283418500001 ER PT J AU Balcazar, H Alvarado, M Cantu, F Pedregon, V Fulwood, R AF Balcazar, Hector Alvarado, Matilde Cantu, Frank Pedregon, Veronica Fulwood, Robert TI A Promotora de Salud Model for Addressing Cardiovascular Disease Risk Factors in the US-Mexico Border Region SO PREVENTING CHRONIC DISEASE LA English DT Article AB Introduction In 2002, the National Heart, Lung, and Blood Institute partnered with the Health Resources and Services Administration's (HRSA's) Bureau of Primary Health Care and Office of Rural Health Policy to address cardiovascular health in the US-Mexico border region. From 2003 through 2005, the 2 agencies agreed to conduct an intervention program using Salud para su Corazon with promotores de salud (community health workers) in high-risk Hispanic communities served by community health centers (CHCs) in the border region to reduce risk factors and improve health behaviors. Methods Promotores de salud from each CHC delivered lessons from the curriculum Your Heart, Your Life. Four centers implemented a 1-group pretest-posttest study design. Educational sessions were delivered for 2 to 3 months. To test Salud para su Corazon-HRSA health objectives, the CHCs conducted the program and assessed behavioral and clinical outcomes at baseline, 3 months, 6 months, and 12 months after the intervention. A 2-sample paired t test and analyses of variance were used to evaluate differences from baseline to postintervention. Results Changes in heart-healthy behaviors were observed, as they have been in previous Salud para su Corazon studies, lending credibility to the effectiveness of a promotores de salud program in a clinical setting. Positive changes were also observed in low-density lipoprotein cholesterol level, triglyceride level, waist circumference, diastolic blood pressure, weight, and glycated hemoglobin (HbA1c). Conclusion Results suggest that integrating promotores de salud into clinical practices is a promising strategy for culturally competent and effective service delivery. Promotores de salud build coalitions and partnerships in the community. The Salud para su Corazon-HRSA initiative was successful in helping to develop an infrastructure to support a promotores de salud workforce in the US-Mexico border region. C1 [Alvarado, Matilde; Fulwood, Robert] NHLBI, NIH, Bethesda, MD 20892 USA. [Cantu, Frank] US Hlth Resources & Serv Adm, Rockville, MD 20857 USA. [Pedregon, Veronica] Univ Calif San Francisco, San Francisco, CA 94143 USA. RP Balcazar, H (reprint author), Univ Texas Hlth Sci Ctr Houston, Sch Publ Hlth, El Paso Reg Campus,1100 N Stanton St,Ste 100, El Paso, TX 79902 USA. EM Hector.G.Balcazar@uth.tmc.edu FU NHLBI; HRSA FX We acknowledge the following community health centers and their representatives: CSV, Melissa Aguirre; NCHS, Maria Banuelos; GCHC, Lourdes Rangel; MCHC, Rosi Piper. We also recognize all of the promotores from the various community health centers who participated in the project. Lastly, we acknowledge funding for this project by NHLBI and HRSA. NR 13 TC 23 Z9 23 U1 1 U2 4 PU CENTERS DISEASE CONTROL PI ATLANTA PA 1600 CLIFTON RD, ATLANTA, GA 30333 USA SN 1545-1151 J9 PREV CHRONIC DIS JI Prev. Chronic Dis. PD JAN PY 2009 VL 6 IS 1 AR A02 PG 8 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA V20RU UT WOS:000208157900002 PM 19080008 ER PT J AU Boyington, JEA Schoster, B Martin, KR Shreffler, J Callahan, LF AF Boyington, Josephine E. A. Schoster, Britta Martin, Kathryn Remmes Shreffler, Jack Callahan, Leigh F. TI Perceptions of Individual and Community Environmental Influences on Fruit and Vegetable Intake, North Carolina, 2004 SO PREVENTING CHRONIC DISEASE LA English DT Article ID PHYSICAL-ACTIVITY; FOOD CHOICE; CARE; CONSUMPTION; HABITS; IMPACT AB Introduction Increases in obesity and other chronic conditions continue to fuel efforts for lifestyle behavior changes. However, many strategies do not address the impact of environment on lifestyle behaviors, particularly healthy dietary intake. This study explored the perceptions of environment on intake of fruits and vegetables in a cohort of 2,479 people recruited from 22 family practices in North Carolina. Methods Participants were administered a health and social demographic survey. Formative assessment was conducted on a subsample of 32 people by using focus groups, semistructured individual interviews, community mapping, and photographs. Interviews and discussions were transcribed and content was analyzed using ATLAS.ti version 5. Survey data were evaluated for means, frequencies, and group differences. Results The 2,479 participants had a mean age of 52.8 years, mean body mass index (BMI) of 29.4, and were predominantly female, white, married, and high school graduates. The 32 subsample participants were older, heavier, and less educated. Some prevalent perceptions about contextual factors related to dietary intake included taste-bud fatigue (boredom with commonly eaten foods), life stresses, lack of forethought in meal planning, current health status, economic status, the ability to garden, lifetime dietary exposure, concerns about food safety, contradictory nutrition messages from the media, and variable work schedules. Conclusion Perceptions about intake of fruits and vegetables intake are influenced by individual (intrinsic) and community (extrinsic) environmental factors. We suggest approaches for influencing behavior and changing perceptions using available resources. C1 [Martin, Kathryn Remmes] Univ N Carolina, Gillings Sch Publ Hlth, Thurston Arthrit Res Ctr, Inst Aging, Chapel Hill, NC USA. [Callahan, Leigh F.] Univ N Carolina, Thurston Arthrit Res Ctr, Dept Med, Dept Orthoped,Dept Social Med, Chapel Hill, NC USA. RP Boyington, JEA (reprint author), NINR, NIH, 1 Democracy Plaza,6701 Democracy Blvd,Suite 710, Bethesda, MD 20892 USA. EM boyingtonje@mail.nih.gov FU National Institute of Arthritis and Musculoskeletal and Skin Diseases [5P60-AR49465-01, 5P60-AR49465-04S1]; National Institutes of Health; National Center on Minority Health and Health Disparities [R24 MD000167]; Department of Health and Human Services, Agency for Healthcare Research and Quality [R24 HS013353]; National Institute on Aging [5-T32-AG00272]; Arthritis Foundation Doctoral Dissertation Award; ACR REF FX This study was funded by National Institute of Arthritis and Musculoskeletal and Skin Diseases grant no. 5P60-AR49465-01. Dr Boyington was supported by the National Institute of Arthritis and Musculoskeletal and Skin Diseases grant no. 5P60-AR49465-04S1, National Institutes of Health, the National Center on Minority Health and Health Disparities grant no. R24 MD000167, and the Department of Health and Human Services, Agency for Healthcare Research and Quality R24 HS013353. Ms Remmes Martin was supported by the Carolina Program on Health and Aging Research Predoctoral Fellowship (National Institute on Aging grant no. 5-T32-AG00272), the Arthritis Foundation Doctoral Dissertation Award, and the ACR REF Health Professional Graduate Student Research Preceptorship Award. NR 34 TC 6 Z9 6 U1 0 U2 7 PU CENTERS DISEASE CONTROL PI ATLANTA PA 1600 CLIFTON RD, ATLANTA, GA 30333 USA SN 1545-1151 J9 PREV CHRONIC DIS JI Prev. Chronic Dis. PD JAN PY 2009 VL 6 IS 1 AR A04 PG 15 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA V20RU UT WOS:000208157900004 PM 19080010 ER PT J AU Wolf, RL Lepore, SJ Vandergrift, JL Basch, CE Yaroch, AL AF Wolf, Randi L. Lepore, Stephen J. Vandergrift, Jonathan L. Basch, Charles E. Yaroch, Amy L. TI Tailored telephone education to promote awareness and adoption of fruit and vegetable recommendations among urban and mostly immigrant black men: A randomized controlled trial SO PREVENTIVE MEDICINE LA English DT Article DE Diet; Randomized clinical trial; Telephone education; Fruits and vegetables; Men; Minority; Immigrant population ID UNITED-STATES; INCREASE CONSUMPTION; DIET INTERVENTION; AFRICAN DIASPORA; HEALTH; ADULTS; QUESTIONNAIRE; EFFICACY; CANCER; STAGE AB Background. Fruit and vegetable (FV) intake in black men are far below national recommendations. Methods. Urban, primarily immigrant, black men (n=490) from the New York City metropolitan area participating in the Cancer Awareness and Prevention (CAP) Trial (2005-2007) were randomly assigned to one of two intervention groups: 1) FV Education (FVE) or 2) Prostate Education (PE). Both interventions entailed a mailed brochure plus two tailored telephone education (TTE) calls. Outcomes, measured at baseline and at eight months, included knowledge of FV recommendations, perceived benefits, stage of readiness to adopt recommendations and self-reported FV consumption. Results. At follow-up. the WE group consumed an average of 1.2 more FV servings per day than the PE group (P<0.001; adjusted for baseline). The FVE group also demonstrated increases in knowledge about recommended FV amounts (P<0.01) and appropriate serving sizes (P<0.05), and in the percent of participants moving from a lower to a higher stage of readiness to adopt FV recommendations (P<0.05). The FVE group did not demonstrate increases in knowledge related to the importance of eating a colorful variety or in the ability to name potential health benefits. Conclusions. TTE can be a practical and moderately effective intervention for raising awareness of FV recommendations and for Promoting FV consumption in urban and primarily immigrant black men. (C) 2008 Elsevier Inc. All rights reserved. C1 [Wolf, Randi L.; Basch, Charles E.] Columbia Univ, Teachers Coll, Dept Hlth & Behav Studies, New York, NY 10027 USA. [Lepore, Stephen J.; Vandergrift, Jonathan L.] Temple Univ, Dept Publ Hlth, Philadelphia, PA 19122 USA. [Yaroch, Amy L.] NCI, Div Canc Control & Populat Sci, Rockville, MD USA. RP Wolf, RL (reprint author), Columbia Univ, Teachers Coll, Dept Hlth & Behav Studies, New York, NY 10027 USA. EM wolf@tc.columbia.edu FU National Cancer Institute of the National Institutes of Health [R01 CA104223] FX This research was supported by grant R01 CA104223 from the National Cancer Institute of the National Institutes of Health. We acknowledge all members of the Cancer Awareness and Prevention (CAP) trial research team, the Data Safety and Monitoring Board members, and the participants. A special thanks to research assistants Melissa Godfrey, Stephanie Brazis, Lindsay Wetmore-Arkader, Elizabeth McGinty and Gabriel Pietrzak. NR 57 TC 17 Z9 17 U1 2 U2 4 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0091-7435 J9 PREV MED JI Prev. Med. PD JAN PY 2009 VL 48 IS 1 BP 32 EP 38 DI 10.1016/j.ypmed.2008.10.015 PG 7 WC Public, Environmental & Occupational Health; Medicine, General & Internal SC Public, Environmental & Occupational Health; General & Internal Medicine GA 401DE UT WOS:000262918000006 PM 19010349 ER PT S AU Menezes, LF Germino, GG AF Menezes, Luis F. Germino, Gregory G. BE Sloboda, RD TI Polycystic Kidney Disease, Cilia, and Planar Polarity SO PRIMARY CILIA SE Methods in Cell Biology LA English DT Review; Book Chapter ID BARDET-BIEDL-SYNDROME; RIGHT AXIS DETERMINATION; WNT SIGNALING PATHWAYS; BASAL BODY DYSFUNCTION; CELL POLARITY; CYST FORMATION; TRANSGENIC MICE; GENE-PRODUCT; SUBCELLULAR-LOCALIZATION; INTRACELLULAR CALCIUM AB Cystic kidney diseases are characterized by dilated or cystic kidney tubular segments. Changes in planar cell polarity, flow sensing, and/or proliferation have been proposed to explain these disorders. Over the last few years, several groups have suggested that ciliary dysfunction is a central component of cyst formation. We review evidence for and against each of these models, stressing some of the inconsistencies that should be resolved if an accurate understanding of cyst formation is to be achieved. We also comment on data supporting a model in which ciliary function could play different roles at different developmental stages and on the relevance of dissecting potential differences between pathways required for tubule formation and/or maintenance. C1 [Menezes, Luis F.; Germino, Gregory G.] Johns Hopkins Univ, Sch Med, Dept Med, Baltimore, MD 21205 USA. [Germino, Gregory G.] NIDDKD, NIH, Bethesda, MD 20892 USA. RP Menezes, LF (reprint author), Johns Hopkins Univ, Sch Med, Dept Med, Baltimore, MD 21205 USA. RI Menezes, Luis Fernando/C-7286-2015; OI Germino, Gregory/0000-0002-3609-5588 FU Intramural NIH HHS; NIDDK NIH HHS [R37DK48006] NR 97 TC 20 Z9 20 U1 0 U2 0 PU ELSEVIER ACADEMIC PRESS INC PI SAN DIEGO PA 525 B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 USA SN 0091-679X BN 978-0-12-375024-2 J9 METHOD CELL BIOL JI Methods Cell Biol. PY 2009 VL 94 BP 273 EP + DI 10.1016/S0091-679X(08)94014-0 PG 30 WC Cell Biology SC Cell Biology GA BMN63 UT WOS:000272975500015 PM 20362096 ER PT J AU Colbert, RA Delay, ML Layh-Schmitt, G Sowders, DP AF Colbert, Robert A. DeLay, Monica L. Layh-Schmitt, Gerlinde Sowders, Dawn P. TI HLA-B27 misfolding and spondyloarthropathies SO PRION LA English DT Review DE ankylosing spondylitis; arthritis; protein misfolding; unfolded protein response; interleukin (IL)-17; cytokines ID MHC CLASS-I; UNFOLDED PROTEIN RESPONSE; ENDOPLASMIC-RETICULUM STRESS; HUMAN MONOCYTIC CELLS; SPONTANEOUS INFLAMMATORY DISEASE; DISULFIDE BOND FORMATION; GENOME-WIDE ASSOCIATION; ANKYLOSING-SPONDYLITIS; TRANSGENIC RATS; T-CELLS AB HLA-B27 plays a central role in the pathogenesis of many spondyloarthropathies and in particular ankylosing spondylitis. The observation that the HLA-B27 heavy chain has a tendency to misfold has raised the possibility that associated diseases may belong in a rapidly expanding category of protein misfolding disorders. The synthesis of the HLA-B27 heavy chain, assembly with beta(2)m and the loading of peptide cargo, occurs in the endoplasmic reticulum ( ER) before transport to the cell surface. The evidence indicates that misfolding occurs in the ER prior to beta(2)m association and peptide optimization and is manifested in the formation of aberrant inter- and intra-chain disulfide bonds and accumulation of heavy chain bound to the chaperone BiP. Enhanced accumulation of misfolded heavy chains during the induction of class I expression by cytokines, can cause ER stress resulting in activation of the unfolded protein response (UPR). Effects of UPR activation on cytokine production are beginning to emerge and may provide important missing links between HLA-B27 misfolding and spondyloarthritis. In this chapter we will review what has been learned about HLA-B27 misfolding in human cells and in the transgenic rat model of spondyloarthritis-like disease, considering it in the context of other protein misfolding disorders. These studies provide a framework to support much needed translational work assessing HLA-B27 misfolding and UPR activation in patient-derived material, its consequences for disease pathogenesis and ultimately how and where to focus intervention strategies. C1 [Colbert, Robert A.; Layh-Schmitt, Gerlinde] NIAMS, NIH, Bethesda, MD 20892 USA. [Colbert, Robert A.; DeLay, Monica L.; Layh-Schmitt, Gerlinde; Sowders, Dawn P.] Cincinnati Childrens Hosp, Med Ctr, Div Rheumatol, Cincinnati, OH USA. RP Colbert, RA (reprint author), NIAMS, NIH, Bldg 10,CRC Rm 1-5142,10 Ctr Dr,MSC 1102, Bethesda, MD 20892 USA. EM colbertra@mac.com NR 129 TC 15 Z9 16 U1 1 U2 4 PU LANDES BIOSCIENCE PI AUSTIN PA 1002 WEST AVENUE, 2ND FLOOR, AUSTIN, TX 78701 USA SN 1933-6896 J9 PRION JI Prion PD JAN-MAR PY 2009 VL 3 IS 1 BP 15 EP 26 PG 12 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 436XM UT WOS:000265449400004 PM 19363299 ER PT B AU Wendling, D Johnson, T Kaske, N AF Wendling, Daniel Johnson, Travis Kaske, Neal BE Hiller, S Justh, K Kyrillidou, M Self, J TI Student Research Behavior: Quantitative and Qualitative Research Findings Presented with Visualizations SO PROCEEDINGS OF THE 2008 LIBRARY ASSESSMENT CONFERENCE: BUILDING EFFECTIVE, SUSTAINABLE, PRACTICAL ASSESSMENT LA English DT Proceedings Paper CT 2008 Library Assessment Conference CY AUG 04-07, 2008 CL Seattle, WA SP Univ Virgina Library, Assoc Res Libraries, Univ Washington Libraries ID INFORMATION; LIBRARY AB The authors investigated the information-seeking patterns of 650 college students at the University of Maryland, College Park and explored ways to generate knowledge about research behaviors. Through focus groups and individual interviews, students from a wide variety of matriculation levels and subject areas described the tools they used and the order of use. Construction of the interview analysis application is described here, including interviewing techniques, inter-view form, results coding sheet, application structure, and screen shots from a Web-based prototype application that renders tables, charts, and graphs about student research behavior from the data set. This methodology helps analyze information-seeking behavior data regarding library and non-library, and Internet/non-Internet resource use. It can make comparison of this dataset with other datasets possible, and can help track emergent behaviors and tool use in the future. The contents of this presentation reflect the views of the authors who are responsible for the opinions, facts, and the accuracy of the data presented. The contents do not necessarily reflect the official views or policies of the National Library of Medicine, National Oceanic and Atmospheric Administration, or University of Maryland Libraries. C1 [Wendling, Daniel] Natl Lib Med, Bethesda, MD 20894 USA. NR 34 TC 0 Z9 0 U1 1 U2 1 PU ASSOC RESEARCH LIBRARIES PI WASHINGTON PA 21 DUPONT CIRCLE, NW, SUITE 800, WASHINGTON, DC 20036 USA BN 978-1-59407-814-9 PY 2009 BP 289 EP 306 PG 18 WC Information Science & Library Science SC Information Science & Library Science GA BJG46 UT WOS:000265657500038 ER PT S AU Liu, HC Tsai, HC Liu, SW AF Liu, Hsiang-Chuan Tsai, Hsien-Chang Liu, Shin-Wu BE Lagakos, S Perlovsky, L Jha, M Covaci, B Zaharim, A Mastorakis, N TI A novel predicting algorithm for Thermostable Proteins based on Hurst exponent and Maximized L-measure SO PROCEEDINGS OF THE AMERICAN CONFERENCE ON APPLIED MATHEMATICS: RECENT ADVANCES IN APPLIED MATHEMATICS SE Mathematics and Computers in Science and Engineering LA English DT Proceedings Paper CT American Conference on Applied Mathematics CY JAN 27-29, 2010 CL Harvard Univ, Cambridge, MA SP WSEAS HO Harvard Univ DE Hurst exponent; Lambda-measure; P-measure; L-measure; Maximized L-measure ID POPS AB Establishing a good algorithm for predicting temperature of thermostable proteins is an important issue. In this study, a new thermostable proteins prediction method by using Hurst exponent and Choquet integral regression model with respect to maximized L-measure is proposed. The main idea of this method is to integrate the physicochemical properties, long term memory property and Choquet integral regression model with respect to maximized L-measure for amino symbolic sequences of different lengths. For evaluating the performance of this new algorithm, a 5-fold Cross-Validation MSE is conducted. Experimental result shows that this new prediction algorithm is better than the Choquet integral regression model with respect to other well known fuzzy measure, Lambda-measure, P-measure, and L-measure, respectively and the traditional prediction models, ridge regression and multiple linear regression models, respectively. C1 [Liu, Hsiang-Chuan] Asia Univ, Dept Bioinformat, 500 Lioufeng Rd, Wufeng 41354, Taichung County, Taiwan. [Tsai, Hsien-Chang] Natl Changhua Univ Educ, Dept Biol, Changhua 50001, Taiwan. [Liu, Shin-Wu] Natl Inst Hlth, Lab Viral Diseases, Bethesda, MD 20892 USA. RP Liu, HC (reprint author), Asia Univ, Dept Bioinformat, 500 Lioufeng Rd, Wufeng 41354, Taichung County, Taiwan. EM lhc@asia.edu.tw; bihft@cc.ncue.edu.tw; liushin@mail.nih.gov FU National Science Council grant of Taiwan Government [NSC 98-2410-H-468-014] FX This paper is partially supported by the National Science Council grant of Taiwan Government (NSC 98-2410-H-468-014) NR 14 TC 0 Z9 0 U1 0 U2 0 PU WORLD SCIENTIFIC AND ENGINEERING ACAD AND SOC PI ATHENS PA AG LOANNOU THEOLOGOU 17-23, 15773 ZOGRAPHOU, ATHENS, GREECE SN 1792-4308 BN 978-960-474-150-2 J9 MATH COMPUT SCI ENG PY 2009 BP 304 EP + PG 2 WC Mathematics, Applied SC Mathematics GA BPM82 UT WOS:000279344900044 ER PT B AU Lin, DC Shreiber, DI Dimitriadis, EK Horkay, F AF Lin, David C. Shreiber, David I. Dimitriadis, Emilios K. Horkay, Ferenc GP ASME TI A HYPERELASTIC CONTACT MODEL FOR THE INDENTATION OF CHONDROCYTES AND CARTILAGE EXTRACELLULAR MATRIX SO PROCEEDINGS OF THE ASME SUMMER BIOENGINEERING CONFERENCE 2008, PTS A AND B LA English DT Proceedings Paper CT ASME Summer Bioengineering Conference CY JUN 25-29, 2008 CL Marco Isl, FL SP Amer Soc Mech Engineers, Bioengn Div ID ATOMIC-FORCE MICROSCOPY; ARTICULAR-CARTILAGE; ZONE C1 [Lin, David C.; Horkay, Ferenc] NICHHD, Sect Tissue Biophys & Biomimet, NIH, Bethesda, MD 20892 USA. RP Lin, DC (reprint author), NICHHD, Sect Tissue Biophys & Biomimet, NIH, Bethesda, MD 20892 USA. OI Shreiber, David/0000-0001-8248-419X NR 5 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC MECHANICAL ENGINEERS PI NEW YORK PA THREE PARK AVENUE, NEW YORK, NY 10016-5990 USA BN 978-0-7918-4321-5 PY 2009 BP 1069 EP 1070 PG 2 WC Engineering, Biomedical SC Engineering GA BIW31 UT WOS:000263364700535 ER PT B AU Korecki, CL Walter, BA Godburn, KE Iatridis, JC AF Korecki, Casey L. Walter, Benjamin A. Godburn, Karolyn E. Iatridis, James C. GP ASME TI ASYMMETRIC LOADING PROMOTES EARLY SIGNS OF INTERVERTEBRAL DISC DEGENERATION IN LARGE ANIMAL ORGAN CULTURE SO PROCEEDINGS OF THE ASME SUMMER BIOENGINEERING CONFERENCE - 2009, PT A AND B LA English DT Proceedings Paper CT ASME Summer Bioengineering Conference CY JUN 17-21, 2009 CL Lake Tahoe, CA SP ASME Bioengn Div C1 [Korecki, Casey L.] NIAMSD, Cartilage Biol & Orthopaed Branch, NIH, US Dept HHS, Bethesda, MD 20892 USA. RP Korecki, CL (reprint author), NIAMSD, Cartilage Biol & Orthopaed Branch, NIH, US Dept HHS, Bethesda, MD 20892 USA. NR 4 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC MECHANICAL ENGINEERS PI NEW YORK PA THREE PARK AVENUE, NEW YORK, NY 10016-5990 USA BN 978-0-7918-4891-3 PY 2009 BP 151 EP 152 PG 2 WC Cell & Tissue Engineering; Engineering, Biomedical SC Cell Biology; Engineering GA BPV38 UT WOS:000280089000076 ER PT B AU Lin, DC Horkay, F AF Lin, David C. Horkay, Ferenc GP ASME TI MAPPING THE ELASTIC AND OSMOTIC PROPERTIES OF CARTILAGE EXTRACELLULAR MATRIX SO PROCEEDINGS OF THE ASME SUMMER BIOENGINEERING CONFERENCE - 2009, PT A AND B LA English DT Proceedings Paper CT ASME Summer Bioengineering Conference CY JUN 17-21, 2009 CL Lake Tahoe, CA SP ASME Bioengn Div ID GELS C1 [Lin, David C.; Horkay, Ferenc] NIH, Sect Tissue Biophys & Biomimet, Bethesda, MD 20892 USA. RP Lin, DC (reprint author), NIH, Sect Tissue Biophys & Biomimet, Bldg 10, Bethesda, MD 20892 USA. NR 6 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC MECHANICAL ENGINEERS PI NEW YORK PA THREE PARK AVENUE, NEW YORK, NY 10016-5990 USA BN 978-0-7918-4891-3 PY 2009 BP 677 EP 678 PG 2 WC Cell & Tissue Engineering; Engineering, Biomedical SC Cell Biology; Engineering GA BPV38 UT WOS:000280089000339 ER PT J AU Ding, XY Patel, M Chan, CC AF Ding, Xiaoyan Patel, Mrinali Chan, Chi-Chao TI Molecular pathology of age-related macular degeneration SO PROGRESS IN RETINAL AND EYE RESEARCH LA English DT Review DE Age-related macular degeneration; Inflammation; Single nucleotide polymorphism; Genetics Retinal pigment epithelium; Retinal photoreceptors; Drusen; Vascular endothelial growth factor; Bruch's membrane; Molecular pathology ID COMPLEMENT FACTOR-H; RETINAL-PIGMENT EPITHELIUM; C-REACTIVE PROTEIN; EXPERIMENTAL CHOROIDAL NEOVASCULARIZATION; APOLIPOPROTEIN-E GENE; BLUE MOUNTAINS EYE; HTRA1 PROMOTER POLYMORPHISM; MITOCHONDRIAL-DNA DAMAGE; CASE-CONTROL SAMPLES; GROWTH-FACTOR-BETA AB Age-related macular degeneration (AMD) is a leading cause of irreversible blindness in the world. Although the etiology and pathogenesis of AMD remain largely unclear, a complex interaction of genetic and environmental factors is thought to exist. AMD pathology is characterized by degeneration involving the retinal photoreceptors, retinal pigment epithelium, and Bruch's membrane, as well as, in some cases, alterations in choroidal capillaries. Recent research on the genetic and molecular underpinnings of AMD brings to light several basic molecular pathways and pathophysiological processes that might mediate AMD risk, progression, and/or response to therapy. This review summarizes, in detail, the molecular pathological findings in both humans and animal models, including genetic variations in CFH, CX3CR1, and ARMS2/HtrA1, as well as the role of numerous molecules implicated in inflammation, apoptosis, cholesterol trafficking, angiogenesis, and oxidative stress. Published by Elsevier Ltd. C1 [Ding, Xiaoyan; Patel, Mrinali; Chan, Chi-Chao] NEI, Immunopathol Sect, Immunol Lab, Bethesda, MD 20892 USA. [Ding, Xiaoyan] Sun Yat Sen Univ, Zhongshan Ophthalm Ctr, Guangzhou 510060, Guangdong, Peoples R China. [Patel, Mrinali] Howard Hughes Med Inst, Chevy Chase, MD USA. RP Chan, CC (reprint author), NEI, Immunopathol Sect, Immunol Lab, 10 Ctr Dr,10-10N103, Bethesda, MD 20892 USA. EM chanc@nei.nih.gov FU NEI Intramural Research Program FX We would like to thank Dr. Robert B. Nussenblatt for his critical review. The support for this study was provided by the NEI Intramural Research Program. NR 209 TC 258 Z9 268 U1 12 U2 73 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 1350-9462 J9 PROG RETIN EYE RES JI Prog. Retin. Eye Res. PD JAN PY 2009 VL 28 IS 1 BP 1 EP 18 DI 10.1016/j.preteyeres.2008.10.001 PG 18 WC Ophthalmology SC Ophthalmology GA 420RF UT WOS:000264306200001 PM 19026761 ER PT J AU Sublette, ME Milak, MS Hibbeln, JR Freed, PJ Oquendo, MA Malone, KM Parsey, RV Mann, JJ AF Sublette, M. Elizabeth Milak, Matthew S. Hibbeln, Joseph R. Freed, Peter J. Oquendo, Maria A. Malone, Kevin M. Parsey, Ramin V. Mann, J. John TI Plasma polyunsaturated fatty acids and regional cerebral glucose metabolism in major depression SO PROSTAGLANDINS LEUKOTRIENES AND ESSENTIAL FATTY ACIDS LA English DT Article DE Major Depressive Disorder; Bipolar Disorder; PET; Docosahexaenoic acid; Arachidonic acid; Eicosapentaenoic acid; PUFA ID POSITRON-EMISSION-TOMOGRAPHY; POSTMORTEM ORBITOFRONTAL CORTEX; BLOOD-CELL MEMBRANES; RHESUS-MONKEY; DOCOSAHEXAENOIC ACID; ARACHIDONIC-ACID; BIPOLAR DISORDER; SEROTONERGIC CHALLENGE; FRONTAL-CORTEX; PREFRONTAL CONNECTIONS AB Deficiencies in polyunsaturated essential fatty acids (PUFA) are implicated in mood disorders, although mechanisms of action and regional specificity in the brain are unknown. We hypothesized that plasma phospholipid PUFA levels are correlated with regionally specific relative cerebral metabolic rates of glucose (rCMRglu). Medication-free depressed subjects (N=29) were studied using [(18)F]-fluoro-2-deoxyglucose positron emission tomography. Docosahexaenoic acid (22:6n-3), arachidonic acid (20:4n-6), and eicosapentaenoic acid (20:5n-3) were assessed as a percentage of total phospholipid PUFA (DHA%, AA%, and EPA%, respectively). DHA% and AA% correlated positively with rCMRglu in temporoparietal cortex. In addition, DHA% correlated negatively with rCMRglu in prefrontal cortex and anterior cingulate. No correlations were seen with EPA%. Thus, under conditions of low plasma DHA, rCMRglu was higher in temporoparietal cortex and lower in anterior cingulate/prefrontal cortex. Opposing effects of DHA on these regions is a hypothesis that could be addressed in future prospective studies with n-3 supplementation. This pilot study is the first to demonstrate fatty acid and regionally specific correlations in the brain between plasma PUFA and rCMRglu in humans. (C) 2008 Elsevier Ltd. All rights reserved. C1 [Sublette, M. Elizabeth; Milak, Matthew S.; Freed, Peter J.; Oquendo, Maria A.; Parsey, Ramin V.; Mann, J. John] Columbia Univ, New York State Psychiat Inst, Dept Mol Imaging & Neuropathol, New York, NY 10032 USA. [Sublette, M. Elizabeth; Milak, Matthew S.; Freed, Peter J.; Oquendo, Maria A.; Parsey, Ramin V.; Mann, J. John] Columbia Univ, Dept Psychiat, New York, NY 10032 USA. [Mann, J. John] Columbia Univ, Dept Radiol, New York, NY 10032 USA. [Hibbeln, Joseph R.] NIAAA, NIH, Bethesda, MD USA. [Malone, Kevin M.] Univ Coll Dublin, Sch Med & Med Sci, Dublin, Ireland. RP Sublette, ME (reprint author), Columbia Univ, New York State Psychiat Inst, Dept Mol Imaging & Neuropathol, 1051 Riverside Dr,Unit 42, New York, NY 10032 USA. EM es2316@columbia.edu RI Sublette, M/A-8391-2009; Milak, Matthew/Q-7170-2016; OI Sublette, M/0000-0001-7378-4262; Malone, Kevin M/0000-0001-5665-4706 FU NCRR NIH HHS [M01 RR000645, M01 RR000645-280727, RR00645]; NIMH NIH HHS [MH40695, MH62185, P50 MH062185, P50 MH062185-09, R01 MH040695, R01 MH040695-17, R01 MH048514] NR 97 TC 40 Z9 41 U1 4 U2 9 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0952-3278 J9 PROSTAG LEUKOTR ESS JI Prostaglandins Leukot. Essent. Fatty Acids PD JAN PY 2009 VL 80 IS 1 BP 57 EP 64 DI 10.1016/j.plefa.2008.11.004 PG 8 WC Biochemistry & Molecular Biology; Cell Biology; Endocrinology & Metabolism SC Biochemistry & Molecular Biology; Cell Biology; Endocrinology & Metabolism GA 422NH UT WOS:000264434500008 PM 19128951 ER PT J AU Ramsden, CE Hibbeln, JR Lands, WE AF Ramsden, Christopher E. Hibbeln, Joseph R. Lands, William E. TI Letter to the Editor re: Linoleic acid and coronary heart disease. SO PROSTAGLANDINS LEUKOTRIENES AND ESSENTIAL FATTY ACIDS LA English DT Letter C1 [Ramsden, Christopher E.] Univ N Carolina, Sch Med, Chapel Hill, NC 27599 USA. [Hibbeln, Joseph R.] NIH, Lab Membrane Biochem & Biophys, Bethesda, MD 20892 USA. [Hibbeln, Joseph R.] NIAAA, NIH, Bethesda, MD 20892 USA. RP Ramsden, CE (reprint author), Univ N Carolina, Sch Med, CB 7200, Chapel Hill, NC 27599 USA. EM cramsden@med.unc.edu NR 10 TC 3 Z9 3 U1 1 U2 2 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0952-3278 J9 PROSTAG LEUKOTR ESS JI Prostaglandins Leukot. Essent. Fatty Acids PD JAN PY 2009 VL 80 IS 1 BP 77 EP 77 DI 10.1016/j.plefa.2008.12.002 PG 1 WC Biochemistry & Molecular Biology; Cell Biology; Endocrinology & Metabolism SC Biochemistry & Molecular Biology; Cell Biology; Endocrinology & Metabolism GA 422NH UT WOS:000264434500011 PM 19147338 ER PT J AU Kelly, MP Lee, ST Lee, FT Smyth, FE Davis, ID Brechbiel, MW Scott, AM AF Kelly, Marcus P. Lee, Sze Ting Lee, F. -T. Smyth, Fiona E. Davis, Ian D. Brechbiel, Martin W. Scott, Andrew M. TI Therapeutic Efficacy of Lu-177-CHX-A ''-DTPA-hu3S193 Radioimmunotherapy in Prostate Cancer Is Enhanced by EGFR Inhibition or Docetaxel Chemotherapy SO PROSTATE LA English DT Article DE hu3S193; prostate cancer; radioimmunotherapy; combined modality ID EPIDERMAL-GROWTH-FACTOR; HUMANIZED MONOCLONAL-ANTIBODY; PHASE-I TRIAL; COMBINED-MODALITY RADIOIMMUNOTHERAPY; LEWIS-Y ANTIGEN; SOLID TUMORS; COLORECTAL-CARCINOMA; MEMBRANE ANTIGEN; BREAST-CANCER; LUNG-CANCER AB BACKGROUND. This study investigated the biodistribution and therapeutic efficacy of Lutetium-177 (Lu-177) radiolabeled anti-Lewis Y monoclonal antibody hu3S193 radioimmnunotherapy (RIT) in mice bearing prostate cancer xenografts. The. ability of epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor AG1478 and docetaxel chemotherapy to enhance the efficacy of RIT was also assessed in vivo. METHODS. The in vitro cytotoxicity of Lu-177 labeled hu3S193 on Le(y) positive DUI 45 prostate cancer cells was assessed using proliferation assays, with induction of apoptosis measured by ELISA. The in vivo biodistribution and tumor localization of Lu-177-hu3S193 was assessed ill mice bearing established DU145 tumor xenografts. The efficacy and maximum tolerated dose of Lu-177-hu3S193 RIT in vivo was determined by a dose escalation study. EGFR inhibitor AG1478 or docetaxel chemotherapy was administered at sub-therapeutic doses in conjunction with RIT in vivo. RESULTS. Lu-177-hu3S193 mediated significant induction of cytotoxicity and apoptosis in vitro. In vivo analysis of Lu-177-hu3S193 biodistribution demonstrated specific targeting of DU145 prostate cancer xenografts, with maximal tumor uptake of 33.2 +/- 3.9%ID/g observed at 120 hr post-injection. In RIT studies, Lu-177-hu3S193 caused specific and dose-dependent inhibition of prostate cancer tumor growth. A maximum tolerated dose of 350 mu Ci was determined for Lu-177-hu3S193. Combination of Lu-177-hu3S193 RIT with EGFR inhibitor AG1478 or docetaxel chemotherapy both significantly improved efficacy. CONCLUSIONS. Lu-177-hu3S193 RIT is effective as a single agent in the treatment of Le(y) positive prostate cancer models. The enhancement of RIT by AG1478 or docetaxel indicates the promise of combined modality strategies. Prostate 69: 92-104, 2009. (C) 2008 Wiley-Liss. Inc. C1 [Kelly, Marcus P.; Lee, Sze Ting; Lee, F. -T.; Smyth, Fiona E.; Scott, Andrew M.] Austin Hosp, Melbourne Ctr Clin Sci, Ludwig Inst Canc Res, Tumour Targeting Lab, Heidelberg, Vic 3084, Australia. [Davis, Ian D.] Austin Hosp, Ludwig Inst Canc Res, Urooncol Lab, Heidelberg, Vic 3084, Australia. [Brechbiel, Martin W.] NCI, Radioimmune & Inorgan Chem Sect, Radiat Oncol Branch, NIH, Bethesda, MD 20892 USA. RP Kelly, MP (reprint author), Austin Hosp, Melbourne Ctr Clin Sci, Ludwig Inst Canc Res, Tumour Targeting Lab, 145-163 Studley Rd, Heidelberg, Vic 3084, Australia. EM mpkelly2@hotmail.com RI Davis, Ian/A-1430-2012 OI Davis, Ian/0000-0002-9066-8244 FU NHMRC Program [280912]; NIH; National Cancer Institute; Center for Cancer Research; Melbourne Research Scholarship, University of Melbourne, Melbourne, Australia; Victorian Cancer Agency Clinician Researcher Fellowship FX We thank the staff from the Department of Nuclear Medicine, Austin Hospital, for their assistance in the CT scanning and gamma camera imaging of animals and staff of the Tumour Targeting Program for assistance in biodistribution studies. This work was supported in part by an NH&MRC Program Grant No. 280912 and the Intramural Research Program of the NIH, National Cancer Institute, Center for Cancer Research. MPK was supported by a Melbourne Research Scholarship, University of Melbourne, Melbourne, Australia. IDD is supported in part by a Victorian Cancer Agency Clinician Researcher Fellowship. MWB is supported by the Intramural Research Program of the NIH, National Cancer Institute, Center for Cancer Research. NR 50 TC 23 Z9 23 U1 0 U2 1 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0270-4137 J9 PROSTATE JI Prostate PD JAN 1 PY 2009 VL 69 IS 1 BP 92 EP 104 DI 10.1002/pros.20856 PG 13 WC Endocrinology & Metabolism; Urology & Nephrology SC Endocrinology & Metabolism; Urology & Nephrology GA 390EZ UT WOS:000262148400010 PM 18942092 ER PT S AU Chung, JY Hewitt, SM AF Chung, Joon-Yong Hewitt, Stephen M. BE Kurien, BT Scofield, RH TI Transfer and Multiplex Immunoblotting of a Paraffin Embedded Tissue SO PROTEIN BLOTTING AND DETECTION: METHODS AND PROTOCOLS SE Methods in Molecular Biology LA English DT Article; Book Chapter DE Immunoassay; Histology; Proteomics; Expressional profiling ID LASER CAPTURE MICRODISSECTION; ELECTROPHORESIS; MICROARRAYS; EXPRESSION; PROTEINS; CANCER AB In the functional proteome era, the proteomic profiling of clinicopathologic annotated tissues is an essential step for mining and evaluations of candidate biomarkers for disease. Previously, application of routine proteomic methodologies to clinical tissue specimens has provided unsatisfactory results. Multiplex tissue immunoblotting is a method of transferring proteins from a formalin-fixed, paraffin-embedded tissue section to a stack of membranes which can be applied to a conventional immunoblotting method. A single tissue section can be transferred to up to ten membranes, each of which is probed with antibodies and detected with fluorescent tags. By this approach, total protein and target signals can be simultaneously determined on each membrane; hence each antibody is internally normalized. Phosphorylation-specific antibodies as well as antibodies that do not readily work well with paraffin-embedded tissue are applicable to the membranes, expanding the menu of antibodies that can be utilized with formalin-fixed tissue. This novel platform can provide quantitative detection retaining histomorphologic detail in clinical samples and has great potential to facilitate discovery and development of new diagnostic assays and therapeutic agents. C1 [Chung, Joon-Yong; Hewitt, Stephen M.] NCI, Bethesda, MD 20892 USA. RP Chung, JY (reprint author), NCI, Bethesda, MD 20892 USA. OI Hewitt, Stephen/0000-0001-8283-1788; Chung, Joon-Yong/0000-0001-5041-5982 NR 15 TC 3 Z9 3 U1 0 U2 1 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DR, STE 208, TOTOWA, NJ 07512-1165 USA SN 1064-3745 BN 978-1-934115-73-2 J9 METHODS MOL BIOL JI Methods Mol. Biol. PY 2009 VL 536 BP 139 EP + DI 10.1007/978-1-59745-542-8_16 D2 10.1007/978-1-59745-542-8 PG 11 WC Biochemical Research Methods SC Biochemistry & Molecular Biology GA BKJ86 UT WOS:000268334600016 PM 19378053 ER PT S AU Root, DD Wang, K AF Root, Douglas D. Wang, Kuan BE Walker, JM TI Kinetic Silver Staining of Proteins SO PROTEIN PROTOCOLS HANDBOOK, THIRD EDITION SE Springer Protocols Handbooks LA English DT Article; Book Chapter ID MICROTITER PLATES C1 [Root, Douglas D.] Univ N Texas, Dept Biol Sci, Denton, TX 76203 USA. [Wang, Kuan] NIAMS, Muscle Biol Lab, NIH, LPB, Bethesda, MD USA. RP Root, DD (reprint author), Univ N Texas, Dept Biol Sci, Denton, TX 76203 USA. NR 4 TC 0 Z9 0 U1 0 U2 1 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DR, STE 208, TOTOWA, NJ 07512-1165 USA SN 1949-2448 BN 978-1-60327-474-6 J9 SPRINGER PROTOC HAND PY 2009 BP 51 EP 54 DI 10.1007/978-1-59745-198-7_8 D2 10.1007/978-1-59745-198-7 PG 4 WC Microbiology SC Microbiology GA BLR02 UT WOS:000270829300008 ER PT S AU Lemkin, PF Thornwall, GC Evans, JA AF Lemkin, Peter F. Thornwall, Gregory C. Evans, Jai A. BE Walker, JM TI Comparing 2D Electrophoretic Gels Across Internet Databases: An Open Source Application SO PROTEIN PROTOCOLS HANDBOOK, THIRD EDITION SE Springer Protocols Handbooks LA English DT Article; Book Chapter ID HUMAN PLASMA PROTEOME; SWISS-2DPAGE DATABASE; BIOMARKER DISCOVERY; META-DATABASE; IMAGES; PROTEINS; IDENTIFICATION; MICROARRAYS; PROSPECTS; SOFTWARE C1 [Evans, Jai A.] Lockheed Martin Corp, Washington, DC USA. [Thornwall, Gregory C.] LECB NCI FCRDC, Frederick, MD USA. NR 34 TC 0 Z9 0 U1 2 U2 2 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DR, STE 208, TOTOWA, NJ 07512-1165 USA SN 1949-2448 BN 978-1-60327-474-6 J9 SPRINGER PROTOC HAND PY 2009 BP 409 EP 441 DI 10.1007/978-1-59745-198-7_40 D2 10.1007/978-1-59745-198-7 PG 33 WC Microbiology SC Microbiology GA BLR02 UT WOS:000270829300040 ER PT S AU Miles, AP Saul, A AF Miles, Aaron P. Saul, Allan BE Walker, JM TI Using SDS-PAGE and Scanning Laser Densitometry to Measure Yield and Degradation of Proteins SO PROTEIN PROTOCOLS HANDBOOK, THIRD EDITION SE Springer Protocols Handbooks LA English DT Article; Book Chapter ID POLYACRYLAMIDE-GEL ELECTROPHORESIS; ASSAY C1 [Miles, Aaron P.] George Washington Univ, Dept Microbiol Immunol & Trop Med, Human Hookworm Vaccine Initiat, Washington, DC 20052 USA. [Saul, Allan] NIAID, Lab Malaria & Vector Res, NIH, Bethesda, MD 20892 USA. RP Miles, AP (reprint author), George Washington Univ, Dept Microbiol Immunol & Trop Med, Human Hookworm Vaccine Initiat, Washington, DC 20052 USA. NR 12 TC 1 Z9 1 U1 0 U2 1 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DR, STE 208, TOTOWA, NJ 07512-1165 USA SN 1949-2448 BN 978-1-60327-474-6 J9 SPRINGER PROTOC HAND PY 2009 BP 487 EP 496 DI 10.1007/978-1-59745-198-7_44 D2 10.1007/978-1-59745-198-7 PG 10 WC Microbiology SC Microbiology GA BLR02 UT WOS:000270829300044 ER PT S AU Root, DD Wang, K AF Root, Douglas D. Wang, Kuan BE Walker, JM TI Copper Iodide Staining of Proteins and Its Silver Enhancement SO PROTEIN PROTOCOLS HANDBOOK, THIRD EDITION SE Springer Protocols Handbooks LA English DT Article; Book Chapter ID MEMBRANES C1 [Root, Douglas D.] Univ N Texas, Dept Biol Sci, Denton, TX 76203 USA. [Wang, Kuan] NIAMS, Muscle Biol Lab, NIH, LPB, Bethesda, MD USA. RP Root, DD (reprint author), Univ N Texas, Dept Biol Sci, Denton, TX 76203 USA. NR 9 TC 1 Z9 1 U1 0 U2 0 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DR, STE 208, TOTOWA, NJ 07512-1165 USA SN 1949-2448 BN 978-1-60327-474-6 J9 SPRINGER PROTOC HAND PY 2009 BP 723 EP 728 DI 10.1007/978-1-59745-198-7_72 D2 10.1007/978-1-59745-198-7 PG 6 WC Microbiology SC Microbiology GA BLR02 UT WOS:000270829300072 ER PT S AU Makrides, SC Gasbarro, C Bello, JM AF Makrides, Sawas C. Gasbarro, Christina Bello, Job M. BE Walker, JM TI The Use of Quantum Dot Luminescent Probes for Western Blot Analysis SO PROTEIN PROTOCOLS HANDBOOK, THIRD EDITION SE Springer Protocols Handbooks LA English DT Article; Book Chapter ID STAPHYLOCOCCAL PROTEIN-A; RECOMBINANT PROTEINS; BIOLOGICAL DETECTION; ESCHERICHIA-COLI; IMMOBILIZATION; BIOTINYLATION; NANOCRYSTALS; PURIFICATION; SPECIFICITY; SUBSTRATE C1 [Makrides, Sawas C.] NCI, Special Review & Logist Branch, Div Extramural Activ, NIH, Bethesda, MD 20892 USA. [Makrides, Sawas C.] Covance Inc, Chantilly, VA USA. [Gasbarro, Christina; Bello, Job M.] EIC Labs Inc, Norwood, MA 02062 USA. RP Makrides, SC (reprint author), NCI, Special Review & Logist Branch, Div Extramural Activ, NIH, Bethesda, MD 20892 USA. NR 25 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 1949-2448 BN 978-1-60327-474-6 J9 SPRINGER PROTOC HAND PY 2009 BP 807 EP 818 DI 10.1007/978-1-59745-198-7_79 D2 10.1007/978-1-59745-198-7 PG 12 WC Microbiology SC Microbiology GA BLR02 UT WOS:000270829300079 ER PT S AU Amero, SA James, TC Elgin, SCR AF Amero, Sally Ann James, Tharappel C. Elgin, Sarah C. R. BE Walker, JM TI Production of Antibodies Using Proteins in Gel Bands SO PROTEIN PROTOCOLS HANDBOOK, THIRD EDITION SE Springer Protocols Handbooks LA English DT Article; Book Chapter ID MONOCLONAL-ANTIBODIES; CHROMOSOMAL PROTEIN; DROSOPHILA; GENE C1 [Amero, Sally Ann] NIH, Ctr Sci Review, Bethesda, MD 20892 USA. [Elgin, Sarah C. R.] Washington Univ, Dept Biol, St Louis, MO 63130 USA. RP Amero, SA (reprint author), NIH, Ctr Sci Review, Bldg 10, Bethesda, MD 20892 USA. NR 17 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 1949-2448 BN 978-1-60327-474-6 J9 SPRINGER PROTOC HAND PY 2009 BP 1687 EP 1691 DI 10.1007/978-1-59745-198-7_170 D2 10.1007/978-1-59745-198-7 PG 5 WC Microbiology SC Microbiology GA BLR02 UT WOS:000270829300170 ER PT S AU Hager-Braun, C Tomer, KB AF Hager-Braun, Christine Tomer, Kenneth B. BE Walker, JM TI Determination of Epitopes by Mass Spectrometry SO PROTEIN PROTOCOLS HANDBOOK, THIRD EDITION SE Springer Protocols Handbooks LA English DT Article; Book Chapter ID IMMUNODEFICIENCY-VIRUS TYPE-1; DIFFERENTIAL CHEMICAL-MODIFICATION; MONOCLONAL-ANTIBODY; DISCONTINUOUS EPITOPE; LIMITED PROTEOLYSIS; PROTEIN; PEPTIDE; IDENTIFICATION; COMPLEX; GLYCOPROTEIN C1 [Hager-Braun, Christine] NIEHS, Res Triangle Pk, NC 27709 USA. [Tomer, Kenneth B.] Struct Biol Lab, Mass Spectrometry Grp, Res Triangle Pk, NC USA. RP Hager-Braun, C (reprint author), NIEHS, POB 12233, Res Triangle Pk, NC 27709 USA. NR 34 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 1949-2448 BN 978-1-60327-474-6 J9 SPRINGER PROTOC HAND PY 2009 BP 1859 EP 1872 DI 10.1007/978-1-59745-198-7_197 D2 10.1007/978-1-59745-198-7 PG 14 WC Microbiology SC Microbiology GA BLR02 UT WOS:000270829300197 ER PT J AU Rajapaksha, M Eichler, JF Hajduch, J Anderson, DE Kirk, KL Bann, JG AF Rajapaksha, Maheshinie Eichler, Jack F. Hajduch, Jan Anderson, David E. Kirk, Kenneth L. Bann, James G. TI Monitoring anthrax toxin receptor dissociation from the protective antigen by NMR SO PROTEIN SCIENCE LA English DT Article DE anthrax; protective antigen; histidine; pH; membrane; pore; fluorine ID LETHAL FACTOR; PROTEIN TRANSLOCATION; PORE FORMATION; CHANNEL; BINDING; IDENTIFICATION; COMPLEX; DOMAIN; CELLS AB The binding of the Bacillus anthracis protective antigen (PA) to the host cell receptor is the first step toward the formation of the anthrax toxin, a tripartite set of proteins that include the enzymatic moieties edema factor (EF), and lethal factor (LF). PA is cleaved by a furin-like protease on the cell surface followed by the formation of a donut-shaped heptameric prepore. The prepore undergoes a major structural transition at acidic pH that results in the formation of a membrane spanning pore, an event which is dictated by interactions with the receptor and necessary for entry of EF and LF into the cell. We provide direct evidence using 1-dimensional (13)C-edited (1)H NMR that low pH induces dissociation of the Von-Willebrand factor A domain of the receptor capillary morphogenesis protein 2 (CMG2) from the prepore, but not the monomeric full length PA. Receptor dissociation is also observed using a carbon-13 labeled, 2-fluorohistidine labeled CMG2, consistent with studies showing that protonation of His-121 in CMG2 is not a mechanism for receptor release. Dissociation is likely caused by the structural transition upon formation of a pore from the prepore state rather than protonation of residues at the receptor PA or prepore interface. C1 [Rajapaksha, Maheshinie; Eichler, Jack F.; Bann, James G.] Wichita State Univ, Dept Chem, Wichita, KS 67260 USA. [Eichler, Jack F.] Emory Univ, Oxford Coll, Div Nat Sci & Math, Oxford, GA 30054 USA. [Hajduch, Jan; Kirk, Kenneth L.] Natl Inst Diabet & Kidney Dis, Bioorgan Chem Lab, NIH, Bethesda, MD 20892 USA. [Anderson, David E.] Natl Inst Diabet & Kidney Dis, Prote & Mass Spectrometry Facil, NIH, Bethesda, MD 20892 USA. RP Bann, JG (reprint author), Wichita State Univ, Dept Chem, 1845 Fairmount, Wichita, KS 67260 USA. EM jim.bann@wichita.edu FU Research Sites for Educators postdoctoral fellowship; NIDDK; National Institutes of Health [US4 AJ1057160]; IDeA-COBRE-PSF award (through the University of Kansas) FX The authors thank Dr. Carl Frieden (Washington University in St. Louis) for use of the fluorine cryoprobe and comments on the manuscript, and Dr. Gregory DeKoster for his assistance with the SMRC experiments. They also thank Dr. Jose Rizo Rey (UT-Southwestern) and Dr. Jacob Schaefer (Washington University) for helpful comments on the manuscript. J.F.E. was supported by a Research Sites for Educators postdoctoral fellowship. K.L.K., J.H., and D.E.A were funded by the intramural research program of NIDDK.; National Institutes of Health; Grant number: US4 AJ1057160; Grant sponsor: IDeA-COBRE-PSF award (through the University of Kansas). NR 31 TC 11 Z9 11 U1 0 U2 4 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0961-8368 J9 PROTEIN SCI JI Protein Sci. PD JAN PY 2009 VL 18 IS 1 BP 17 EP 23 DI 10.1002/pro.26 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 396TI UT WOS:000262613700004 PM 19177347 ER PT J AU Lountos, GT Tropea, JE Zhang, D Jobson, AG Pommier, Y Shoemaker, RH Waugh, DS AF Lountos, George T. Tropea, Joseph E. Zhang, Di Jobson, Andrew G. Pommier, Yves Shoemaker, Robert H. Waugh, David S. TI Crystal structure of checkpoint kinase 2 in complex with NSC 109555, a potent and selective inhibitor SO PROTEIN SCIENCE LA English DT Article DE checkpoint kinase inhibitor; structure-assisted drug design; cocrystal structure ID DNA-DAMAGE CHECKPOINT; PROTEIN-KINASE; CHK2 KINASE; CANCER-THERAPY; TUMOR-CELLS; DRUG DESIGN; ACTIVATION; AUTOPHOSPHORYLATION; RADIATION; DOMAIN AB Checkpoint kinase 2 (Chk2), a ser/thr kinase involved in the ATM-Chk2 checkpoint pathway, is activated by genomic instability and DNA damage and results in either arrest of the cell cycle to allow DNA repair to occur or apoptosis if the DNA damage is severe. Drugs that specifically target Chk2 could be beneficial when administered in combination with current DNA-damaging agents used in cancer therapy. Recently, a novel inhibitor of Chk2, NSC 109555, was identified that exhibited high potency (IC(50) = 240 nM) and selectivity. This compound represents a new chemotype and lead for the development of novel Chk2 inhibitors that could be used as therapeutic agents for the treatment of cancer. To facilitate the discovery of new analogs of NSC 109555 with even greater potency and selectivity, we have solved the crystal structure of this inhibitor in complex with the catalytic domain of Chk2. The structure confirms that the compound is an ATP-competitive inhibitor, as the electron density clearly reveals that it occupies the ATP-binding pocket. However, the mode of inhibition differs from that of the previously studied structure of Chk2 in complex with debromohymenialdisine, a compound that inhibits both Chk1 and Chk2. A unique hydrophobic pocket in Chk2, located very close to the bound inhibitor, presents an opportunity for the rational design of compounds with higher binding affinity and greater selectivity. C1 [Lountos, George T.; Tropea, Joseph E.; Zhang, Di; Waugh, David S.] NCI, Macromol Crystallog Lab, Frederick, MD 21702 USA. [Jobson, Andrew G.; Pommier, Yves] NCI, Mol Pharmacol Lab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. [Shoemaker, Robert H.] NCI, Screening Technol Branch, Dev Therapeut Program, Div Canc Treatment & Diag, Frederick, MD 21702 USA. RP Waugh, DS (reprint author), NCI, Macromol Crystallog Lab, POB B, Frederick, MD 21702 USA. EM waughd@ncifcrf.gov RI Lountos, George/B-3983-2015 FU NIH; National Cancer Institute; Center for Cancer Research; U.S. Department of Energy, Office of Science, Office of Basic Energy Sciences [W-31-109-Eng-38] FX NIH, National Cancer Institute, Center for Cancer Research.; Electrospray mass spectrometry experiments were conducted on the LC/ESMS instrument maintained by the Biophysics Resource in the Structural Biophysics Laboratory, Center for Cancer Research, National Cancer Institute at Frederick. X-ray diffraction data were collected at the Southeast Regional Collaborative Access Team (SER-CAT) beamline 22-ID at the Advanced Photon Source, Argonne National Laboratory. Supporting institutions may be found at http://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. NR 53 TC 18 Z9 19 U1 0 U2 4 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0961-8368 J9 PROTEIN SCI JI Protein Sci. PD JAN PY 2009 VL 18 IS 1 BP 92 EP 100 DI 10.1002/pro.16 PG 9 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 396TI UT WOS:000262613700011 PM 19177354 ER PT J AU Degenhardt, L Chiu, WT Conway, K Dierker, L Glantz, M Kalaydjian, A Merikangas, K Sampson, N Swendsen, J Kessler, RC AF Degenhardt, L. Chiu, W. T. Conway, K. Dierker, L. Glantz, M. Kalaydjian, A. Merikangas, K. Sampson, N. Swendsen, J. Kessler, R. C. TI Does the 'gateway' matter? Associations between the order of drug use initiation and the development of drug dependence in the National Comorbidity Study Replication SO PSYCHOLOGICAL MEDICINE LA English DT Article DE Alcohol; cannabis; dependence; gateway; illicit drugs; National Comorbidity Survey Replication; tobacco ID WORLD-HEALTH-ORGANIZATION; MENTAL-HEALTH; CANNABIS USE; GENERAL-POPULATION; YOUNG ADULTHOOD; NCS-R; PROGRESSION; MARIJUANA; ALCOHOL; COHORT AB Background. The 'gateway' pattern of drug initiation describes a normative sequence, beginning with alcohol and tobacco use, followed by cannabis, then other illicit drugs. Previous work has suggested that 'violations' of this sequence may be predictors of later problems but other determinants were not considered. We have examined the role of pre-existing mental disorders and sociodemographics in explaining the predictive effects of violations using data from the US National Comorbidity Survey Replication (NCS-R). Method. The NCS-R is a nationally representative face-to-face household survey of 9282 English-speaking respondents aged 18 years and older that used the World Health Organization (WHO) Composite International Diagnostic Interview (CIDI) to assess DSM-IV mental and substance disorders. Drug initiation was estimated using retrospective age-of-onset reports and 'violations' defined as inconsistent with the normative initiation order. Predictors of violations were examined using multivariable logistic regressions. Discrete-time survival analysis was used to see whether violations predicted progression to dependence. Results. Gateway violations were largely unrelated to later dependence risk, with the exception of small increases in risk of alcohol and other illicit drug dependence for those who initiated use of other illicit drugs before cannabis. Early-onset internalizing disorders were predictors of gateway violations, and both internalizing and externalizing disorders increased the risks of dependence among users of all drugs. Conclusions. Drug use initiation follows a strong normative pattern, deviations from which are not strongly predictive of later problems. By contrast, adolescents who have already developed mental health problems are at risk for deviations from the normative sequence of drug initiation and for the development of dependence. C1 [Degenhardt, L.] Univ New S Wales, Natl Drug & Alcohol Res Ctr, Sydney, NSW 2052, Australia. [Chiu, W. T.; Sampson, N.; Kessler, R. C.] Harvard Univ, Sch Med, Dept Hlth Care Policy, Boston, MA 02115 USA. [Conway, K.] Natl Inst Drug Abuse, Div Epidemiol Serv & Prevent Res, US Natl Inst Hlth, Bethesda, MD USA. [Dierker, L.] Wesleyan Univ, Dept Psychol, Middletown, CT USA. [Kalaydjian, A.; Merikangas, K.] NIMH, Bethesda, MD 20892 USA. [Swendsen, J.] Univ Bordeaux, Psychopathol Res Lab, Bordeaux, France. RP Degenhardt, L (reprint author), Univ New S Wales, Natl Drug & Alcohol Res Ctr, Sydney, NSW 2052, Australia. EM l.degenhardt@unsw.edu.au RI Degenhardt, Louisa/D-4515-2012; OI Degenhardt, Louisa/0000-0002-8513-2218; Conway, Kevin/0000-0002-7638-339X FU National Institute of Mental Health [U01-MH60220]; National Institute of Drug Abuse (NIDA); Substance Abuse and Mental Health Services Administration (SAMHSA); Robert Wood Johnson Foundation [044708]; John W. Alden Trust; National Institutes of Health [K01 DA15454, R01 DA012058]; NIDA (Dierker); Patrick and Catherine Weldon Donaghue Medical Research Foundation; Australian Government Department of Health and Ageing (Degenhardt); Australian National Health and Medical Research Council (NHMRC); US NIMH [R01MH070884]; John D. and Catherine T. MacArthur Foundation; Pfizer Foundation; US Public Health Service [R13-MH066849, R01-MH069864, R01 DA016558]; Fogarty International Center [FIRCA R01-TW006481]; Pan American Health Organization; Eli Lilly and Company; Ortho-McNeil Pharmaceutical, Inc.; GlaxoSmithKline; Bristol-Myers Squibb FX The US National Comorbidity Survey Replication (NCS-R) is supported by the National Institute of Mental Health (NIMH; U01-MH60220) with supplemental support from the National Institute of Drug Abuse (NIDA), the Substance Abuse and Mental Health Services Administration (SAMHSA), the Robert Wood Johnson Foundation (RWJF; Grant 044708), and the John W. Alden Trust. Data analyses and manuscript preparation were undertaken with support from an Intramural Research Program of the National Institutes of Health, NIMH (Kalaydjian, Merikangas), grants K01 DA15454 and R01 DA012058 from the NIDA (Dierker), and an Investigator Award from the Patrick and Catherine Weldon Donaghue Medical Research Foundation (Dierker). The National Drug and Alcohol Research Centre is funded by the Australian Government Department of Health and Ageing (Degenhardt), and Degenhardt is the recipient of an Australian National Health and Medical Research Council (NH&MRC) Senior Research Fellowship. The NCS-R is carried out in conjunction with the World Health Organization World Mental Health (WMH) Survey Initiative. We thank the WMH staff for assistance with instrumentation, fieldwork and data analysis. These activities were supported by the US NIMH (R01MH070884), the John D. and Catherine T. MacArthur Foundation, the Pfizer Foundation, the US Public Health Service (R13-MH066849, R01-MH069864, and R01 DA016558), the Fogarty International Center (FIRCA R01-TW006481), the Pan American Health Organization, Eli Lilly and Company, Ortho-McNeil Pharmaceutical, Inc., GlaxoSmithKline, and Bristol-Myers Squibb. A complete list of WMH publications can be found at www.hcp.med.harvard.edu/wmh/. NR 38 TC 53 Z9 55 U1 2 U2 10 PU CAMBRIDGE UNIV PRESS PI NEW YORK PA 32 AVENUE OF THE AMERICAS, NEW YORK, NY 10013-2473 USA SN 0033-2917 J9 PSYCHOL MED JI Psychol. Med. PD JAN PY 2009 VL 39 IS 1 BP 157 EP 167 DI 10.1017/S0033291708003425 PG 11 WC Psychology, Clinical; Psychiatry; Psychology SC Psychology; Psychiatry GA 396DJ UT WOS:000262572100016 PM 18466664 ER PT J AU Mallinger, AG Frank, E Thase, ME Barwell, MM DiazGranados, N Luckenbaugh, DA Kupfer, DJ AF Mallinger, Alan G. Frank, Ellen Thase, Michael E. Barwell, Michelle M. DiazGranados, Nancy Luckenbaugh, David A. Kupfer, David J. TI Revisiting the Effectiveness of Standard Antidepressants in Bipolar Disorder: Are Monoamine Oxidase Inhibitors Superior? SO PSYCHOPHARMACOLOGY BULLETIN LA English DT Article DE antidepressive agents; bipolar disorder; depressive disorder; clinical trial; monoamine oxidase inhibitors; treatment outcome ID RATING-SCALE; DEPRESSION; IMIPRAMINE; TRANYLCYPROMINE; MOCLOBEMIDE AB Objective: The role of antidepressants in treating bipolar disorder is controversial, and the comparative effectiveness of specific drugs is insufficiently studied. We report here a comparison of monoamine oxidase inhibitors (MAOIs) with the serotonin reuptake inhibitor paroxetine (PAROX). Experimental Design: We conducted a retrospective analysis of data from a larger study, using the first antidepressant trial administered either after entry (n = 46) or after a recurrent episode during study participation (n = 6). Twenty two patients were treated with PAROX and 30 with an MAOI. Durable recovery was determined from Hamilton depression and Young mania scores, based on published criteria. Principal Observations: PAROX treatment led to durable recovery in 27% of patients, a result very similar to the 24% recovery rate found in a recent STEP-BD trial. In contrast, patients treated with an MAOI had a 53% durable recovery rate. Survival analysis showed a significantly faster onset of durable recovery with MAOIs (chi(2) = 4.77, p = 0.029). Among subjects who were able to complete an adequate treatment trial of at least four weeks duration, durable recovery was attained in a significantly greater proportion of those treated with an MAOI (16 of 23, 70%) as compared to PAROX (6 of 18, 33%)(Fisher's Exact Test, p = 0.023). Conclusions: In these patients with bipolar depression, the antidepressant effectiveness of PAROX was unacceptably low, but rates of recovery with MAOIs were significantly higher. Psychopharmacology Bulletin. 2009;42(2):64-74. C1 [Mallinger, Alan G.; Frank, Ellen; Thase, Michael E.; Barwell, Michelle M.; Kupfer, David J.] Univ Pittsburgh, Sch Med, Dept Psychiat, Pittsburgh, PA USA. [Mallinger, Alan G.; DiazGranados, Nancy] NIMH, Intramural Res Program, NIH, Bethesda, MD 20892 USA. [Thase, Michael E.] Univ Penn, Sch Med, Dept Psychiat, Philadelphia, PA 19104 USA. RP Mallinger, AG (reprint author), NIMH, Mood & Anxiety Disorders Program, DIRP, NIH, Bldg 10,Room 3N210,MSC 1290, Bethesda, MD 20892 USA. EM mallingera@mail.nih.gov FU National Institute of Mental Health [MH29618, MH49115, MH30915]; NIH, National Institute of Mental Health FX This research was supported in part by Grants MH29618, MH49115 and MH30915 from the National Institute of Mental Health, and in part by the Intramural Program of the NIH, National Institute of Mental Health. This work was initially performed at the University of Pittsburgh, prior to Dr. Mallinger's official duties as a Government employee. The views expressed in this paper do not necessarily represent the views of the United States Government or any of its agencies. This study is registered with ClinicalTrials.gov (Identifier: NCT00227968). NR 14 TC 12 Z9 13 U1 0 U2 2 PU MEDWORKS MEDIA GLOBAL, LLC PI HERMOS BEACH PA 670 FIFTH STREET, STE A, HERMOS BEACH, CA 90254 USA SN 0048-5764 J9 PSYCHOPHARMACOL BULL JI Psychopharmacol. Bull. PY 2009 VL 42 IS 2 BP 64 EP 74 PG 11 WC Pharmacology & Pharmacy; Psychiatry SC Pharmacology & Pharmacy; Psychiatry GA 641OH UT WOS:000281137100004 PM 19629023 ER PT J AU Meltzer, JA Fonzo, GA Constable, RT AF Meltzer, Jed A. Fonzo, Greg A. Constable, R. Todd TI Transverse patterning dissociates human EEG theta power and hippocampal BOLD activation SO PSYCHOPHYSIOLOGY LA English DT Article DE fMRI; Alpha; Default mode; Negative BOLD; LORETA ID FRONTAL MIDLINE THETA; WORKING-MEMORY TASK; ANTERIOR CINGULATE CORTEX; ALPHA-RHYTHM; GAMMA-OSCILLATIONS; PREFRONTAL CORTEX; VISUAL-CORTEX; PHASE-LOCKING; ELECTROMAGNETIC TOMOGRAPHY; RECOGNITION MEMORY AB Theta oscillations (4-8 Hz) are often modulated in human electroencephalogram (EEG) studies of memory, whereas overlapping frequencies dominate rodent hippocampal EEG. An emerging parallelism between theta reactivity and hippocampal functional magnetic resonance imaging activation has suggested a homology between theta activity in humans and rodents, representing a process of cortico-hippocampal interaction involved in memory. In the present study, we investigated EEG reactivity during performance of a relational memory task that induces a negative hippocampal blood oxygenation level dependent (BOLD) signal change, compared to a nonrelational control condition. Relational trials induced theta increases and alpha decreases. Low Resolution Electromagnetic Brain Tomography estimates localized theta and alpha modulation to frontal midline and parietal midline cortices, respectively, both of which exhibit negative BOLD responses in this task. Thus, theta and alpha dynamics are dissociable from positive BOLD activation, and may, in fact, colocalize with negative BOLD responses. C1 [Meltzer, Jed A.; Constable, R. Todd] Yale Univ, Interdepartmental Neurosci Program, New Haven, CT USA. [Fonzo, Greg A.; Constable, R. Todd] Yale Univ, Dept Diagnost Radiol, New Haven, CT 06510 USA. [Constable, R. Todd] Yale Univ, Dept Biomed Engn, New Haven, CT 06510 USA. [Constable, R. Todd] Yale Univ, Dept Neurosurg, New Haven, CT 06510 USA. RP Meltzer, JA (reprint author), Natl Inst Deafness & Other Commun Disorders, NIH, Bldg 10,Rm 5C410,10 Ctr Dr, Bethesda, MD 20892 USA. EM jed.meltzer@aya.yale.edu OI Meltzer, Jed/0000-0002-4301-1901 FU NIH [R01-NS38467]; American Epilepsy Society FX This research was supported by NIH R01-NS38467 and by a predoctoral fellowship from the American Epilepsy Society (J. A. M.). We thank Ulrich Schridde for helpful comments on the manuscript and Robert Astur for development of the transverse patterning task. NR 90 TC 13 Z9 16 U1 1 U2 2 PU WILEY-BLACKWELL PUBLISHING, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0048-5772 J9 PSYCHOPHYSIOLOGY JI Psychophysiology PD JAN PY 2009 VL 46 IS 1 BP 153 EP 162 DI 10.1111/j.1469-8986.2008.00719.x PG 10 WC Psychology, Biological; Neurosciences; Physiology; Psychology; Psychology, Experimental SC Psychology; Neurosciences & Neurology; Physiology GA 387WW UT WOS:000261983300017 PM 18823411 ER PT J AU Peyk, P Schupp, HT Keil, A Elbert, T Junghofer, M AF Peyk, Peter Schupp, Harald T. Keil, Andreas Elbert, Thomas Junghoefer, Markus TI Parallel processing of affective visual stimuli SO PSYCHOPHYSIOLOGY LA English DT Article DE ERP; Emotion; Attention; Rapid serial visual presentation ID NEURAL MECHANISMS; BRAIN MECHANISMS; ERP ANALYSIS; EMOTION; ATTENTION; PERCEPTION; ACTIVATION; CORTEX; POTENTIALS; AWARENESS AB Event-related potential (ERP) studies of affective picture processing have demonstrated an early posterior negativity (EPN) for emotionally arousing pictures that are embedded in a rapid visual stream. The present study examined the selective processing of emotional pictures while systematically varying picture presentation rates between 1 and 16 Hz. Previous results with presentation rates up to 5 Hz were replicated in that emotional compared to neutral pictures were associated with a greater EPN. Discrimination among emotional and neutral contents was maintained up to 12 Hz. To explore the notion of parallel processing, convolution analysis was used: EPNs generated by linear superposition of slow rate ERPs explained 70%-93% of the variance of measured EPNs, giving evidence for an impressive capacity of parallel affective discrimination in rapid serial picture presentation. C1 [Peyk, Peter] Univ Basel, Dept Psychol, Basel, Switzerland. [Schupp, Harald T.; Elbert, Thomas] Univ Konstanz, Dept Psychol, Constance, Germany. [Keil, Andreas] Univ Florida, NIMH, Ctr Study Emot & Attent, Gainesville, FL USA. [Junghoefer, Markus] Univ Munster, Inst Biomagnetism & Biosignalanalysis, Munster, Germany. RP Peyk, P (reprint author), Univ Basel, Dept Clin Psychol & Psychotherapy, Missionsstr 60-62, CH-4055 Basel, Switzerland. EM peter.peyk@unibas.ch RI Elbert, Thomas/C-8556-2009; Frank, David/E-8213-2012; Keil, Andreas/F-9427-2011 OI Keil, Andreas/0000-0002-4064-1924 FU NIMH NIH HHS [P50 MH072850, P50 MH072850-04] NR 30 TC 22 Z9 23 U1 1 U2 10 PU WILEY-BLACKWELL PUBLISHING, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0048-5772 J9 PSYCHOPHYSIOLOGY JI Psychophysiology PD JAN PY 2009 VL 46 IS 1 BP 200 EP 208 DI 10.1111/j.1469-8986.2008.00755.x PG 9 WC Psychology, Biological; Neurosciences; Physiology; Psychology; Psychology, Experimental SC Psychology; Neurosciences & Neurology; Physiology GA 387WW UT WOS:000261983300022 PM 19055507 ER PT J AU Kuh, D Cooper, R Hardy, R Guralnik, J Richards, M AF Kuh, Diana Cooper, Rachel Hardy, Rebecca Guralnik, Jack Richards, Marcus CA Musculoskeletal Study Team TI Lifetime Cognitive Performance is Associated With Midlife Physical Performance in a Prospective National Birth Cohort Study SO PSYCHOSOMATIC MEDICINE LA English DT Article DE lifetime cognition; physical performance; birth cohort; developmental differences ID LATE ADULTHOOD; GRIP STRENGTH; OLDER-ADULTS; HEALTH; AGE; AMERICANS; VARIABLES; DECLINE; BALANCE; BRAIN AB Objectives: To examine whether measures of cognitive performance across life are related to physical performance at age 53 years, allowing for potential confounders. Methods: In a large representative British birth cohort of men and women (N = 2135) the associations between cognitive performance across life (i.e., standardized cognition scores at ages 15, 43, and 53 years and changes in verbal memory and search speed scores between 43 and 53 years) and measures of physical performance at age 53 years (i.e., standing balance, chair rising, and grip strength) were examined. Adjustments were made for body size, physical activity levels, health status, and socioeconomic conditions at age 53 years. Results: Higher cognitive scores on all childhood and adult tests, and a slower decline in verbal memory and search speed, were associated with better standing balance. Higher verbal fluency scores and a slower decline in verbal memory and search speed were more strongly related than scores on tests of general cognitive ability to chair rising. The relationships between cognitive performance and grip strength were inconsistent and weak. Conclusions: The differential patterns of association found are consistent with the degree to which each is dependent on central nervous system function. Our findings suggest that initial developmental differences as well as shared ageing processes may underlie associations found between cognitive and physical performance. C1 [Kuh, Diana; Cooper, Rachel; Hardy, Rebecca; Richards, Marcus] Royal Free & Univ Coll Med Sch, MRC NSHD, MRC Unit Lifelong Hlth & Ageing, Dept Epidemiol & Publ Hlth, London WC1B 5JU, England. [Guralnik, Jack] NIA, Lab Epidemiol Demog & Biometry, Bethesda, MD 20892 USA. RP Kuh, D (reprint author), Royal Free & Univ Coll Med Sch, MRC NSHD, MRC Unit Lifelong Hlth & Ageing, Dept Epidemiol & Publ Hlth, 33 Bedford Pl, London WC1B 5JU, England. EM d.kuh@nshd.mrc.ac.uk OI Cooper, Rachel/0000-0003-3370-5720 FU Medical Research Council, United Kingdom; Intramural Research Program; National Institute on Aging; NIH FX Supported by the Medical Research Council, United Kingdom and in part by the Intramural Research Program, National Institute on Aging, NIH; MRC (to DK, RC, RH, and MR) and NIA (to J.G.). NR 40 TC 28 Z9 28 U1 1 U2 7 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0033-3174 J9 PSYCHOSOM MED JI Psychosom. Med. PD JAN PY 2009 VL 71 IS 1 BP 38 EP 48 DI 10.1097/PSY.0b013e31818a1620 PG 11 WC Psychiatry; Psychology; Psychology, Multidisciplinary SC Psychiatry; Psychology GA 395ZR UT WOS:000262562500008 PM 19124616 ER PT J AU Rice, SC Zonderman, AB Metter, EJ Najjar, SS Waldstein, SR AF Rice, S. Carrington Zonderman, Alan B. Metter, E. Jeffrey Najjar, Samer S. Waldstein, Shari R. TI Absence of Relation Between Depressive Symptoms and Carotid Intimal Medial Thickness in the Baltimore Longitudinal Study of Aging SO PSYCHOSOMATIC MEDICINE LA English DT Article DE atherosclerosis; carotid intimal medial thickness; depression ID CORONARY HEART-DISEASE; RISK-FACTOR; CARDIOVASCULAR-DISEASE; MYOCARDIAL-INFARCTION; NEGATIVE EMOTIONS; ARTERIAL-WALL; ATHEROSCLEROSIS; ASSOCIATION; PROGRESSION; REFLECTION AB Objective: To examine the relation between longitudinal trajectories of depressive symptoms as well as history of significant symptoms and subsequent carotid intimal media] thickness (IMT) among participants enrolled in the Baltimore Longitudinal Study of Aging and to assess longitudinal covariation of depressive symptoms and carotid IMT over two time points. Prior literature has identified inconsistent cross-sectional associations between depressive symptoms and carotid IMT in healthy persons, and existing longitudinal work has relied on depression assessment at a single time point. Methods: A total of 556 participants (303 women and 253 men), aged 20 to 93 years (mean +/- standard deviation = 55.8 +/- 15.9 years), completed the Center for Epidemiological Studies-Depression (CES-D) scale from one to eight times over I to 15 years. Participants later underwent high-resolution B-mode ultrasonography to assess IMT of the far wall of the common carotid artery. A subset of these participants (n = 68) underwent reassessment of IMT an average of 3.9 years later. Linear and mixed-effects regression models were adjusted for sex, race, education, systolic blood pressure, low-density lipoprotein cholesterol, body mass index, diabetes, smoking, and anti hypertensive, lipid-lowering, and antidepressant medications. Results: There was no relation between trajectory of depressive symptoms or history of significant depressive symptoms and future carotid IMT. There was also no evidence for longitudinal covariation of depressive symptoms and IMT over time. Additional analyses similarly revealed a lack of significant associations. Conclusion: There is no association between depressive symptoms and carotid IMT in the present sample of healthy community-dwelling volunteers. C1 [Rice, S. Carrington; Waldstein, Shari R.] Univ Maryland Baltimore Cty, Dept Psychol, Baltimore, MD 21250 USA. [Rice, S. Carrington; Zonderman, Alan B.; Metter, E. Jeffrey; Najjar, Samer S.] NIA, Intramural Res Program, Baltimore, MD 21224 USA. [Waldstein, Shari R.] NIH, Bethesda, MD 20892 USA. [Waldstein, Shari R.] Univ Maryland, Sch Med, Dept Med, Div Gerontol, Baltimore, MD 21201 USA. [Waldstein, Shari R.] Ctr Geriatr Res Educ & Clin, Baltimore, MD USA. RP Rice, SC (reprint author), Univ Maryland Baltimore Cty, Dept Psychol, 1000 Hilltop Circle, Baltimore, MD 21250 USA. EM rice3@umbc.edu OI Zonderman, Alan B/0000-0002-6523-4778 FU National Institutes of Health FX Supported by The National Institute on Aging Intramural Research Program of the National Institutes of Health (S.C.R., A.B.Z., E.J.M., S.S.N.). NR 32 TC 15 Z9 15 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0033-3174 J9 PSYCHOSOM MED JI Psychosom. Med. PD JAN PY 2009 VL 71 IS 1 BP 70 EP 76 DI 10.1097/PSY.0b013e3181865f73 PG 7 WC Psychiatry; Psychology; Psychology, Multidisciplinary SC Psychiatry; Psychology GA 395ZR UT WOS:000262562500012 PM 18842746 ER PT J AU Wideroff, L Phillips, KA Randhawa, G Ambs, A Armstrong, K Bennett, CL Brown, ML Donaldson, MS Follen, M Goldie, SJ Hiatt, RA Khoury, MJ Lewis, G McLeod, HL Piper, M Powell, I Schrag, D Schulman, KA Scott, J AF Wideroff, Louise Phillips, Kathryn A. Randhawa, Gurvaneet Ambs, Anita Armstrong, Katrina Bennett, Charles L. Brown, Martin L. Donaldson, Molla S. Follen, Michele Goldie, Sue J. Hiatt, Robert A. Khoury, Muin J. Lewis, Graham McLeod, Howard L. Piper, Margaret Powell, Isaac Schrag, Deborah Schulman, Kevin A. Scott, Joan TI A Health Services Research Agenda for Cellular, Molecular and Genomic Technologies in Cancer Care SO PUBLIC HEALTH GENOMICS LA English DT Review DE Genomics; Health services research; Emerging technologies; Translational research ID COST-EFFECTIVENESS ANALYSIS; METASTATIC BREAST-CANCER; REPORTS RADAR PROJECT; ADVERSE DRUG EVENTS; CLINICAL-PRACTICE; RACIAL-DIFFERENCES; CERVICAL-CANCER; PUBLIC-HEALTH; PROPHYLACTIC VACCINES; PROSTATE-CANCER AB Background: In recent decades, extensive resources have been invested to develop cellular, molecular and genomic technologies with clinical applications that span the continuum of cancer care. Methods: In December 2006, the National Cancer Institute sponsored the first workshop to uniquely examine the state of health services research on cancer-related cellular, molecular and genomic technologies and identify challenges and priorities for expanding the evidence base on their effectiveness in routine care. Results: This article summarizes the workshop outcomes, which included development of a comprehensive research agenda that incorporates health and safety endpoints, utilization patterns, patient and provider preferences, quality of care and access, disparities, economics and decision modeling, trends in cancer outcomes, and health-related quality of life among target populations. Conclusions: Ultimately, the successful adoption of useful technologies will depend on understanding and influencing the patient, provider, health care system and societal factors that contribute to their uptake and effectiveness in 'real-world' settings. Copyright (C) 2009 S. Karger AG, Basel C1 [Wideroff, Louise; Ambs, Anita; Brown, Martin L.] NCI, Bethesda, MD 20892 USA. [Phillips, Kathryn A.; Hiatt, Robert A.] Univ Calif San Francisco, San Francisco, CA 94143 USA. [Randhawa, Gurvaneet] Agcy Healthcare Res & Qual, Rockville, MD USA. [Armstrong, Katrina] Univ Penn, Philadelphia, PA 19104 USA. [Bennett, Charles L.] Northwestern Univ, Evanston, IL USA. [Donaldson, Molla S.] George Washington Univ, Washington, DC USA. [Follen, Michele] Univ Texas Houston, MD Anderson Canc Ctr, Houston, TX 77030 USA. [Goldie, Sue J.] Harvard Univ, Boston, MA 02115 USA. [Schrag, Deborah] Dana Farber Canc Inst, Boston, MA 02115 USA. [Khoury, Muin J.] Ctr Dis Control & Prevent, Atlanta, GA USA. [McLeod, Howard L.] Univ N Carolina, Chapel Hill, NC USA. [Piper, Margaret] Blue Cross Blue Shield Assoc Technol Evaluat Ctr, Chicago, IL USA. [Powell, Isaac] Wayne State Univ, Detroit, MI USA. [Schulman, Kevin A.] Duke Univ, Durham, NC USA. [Scott, Joan] Johns Hopkins Univ, Baltimore, MD USA. [Lewis, Graham] Univ York, Heslington, England. RP Wideroff, L (reprint author), Natl Inst Drug Abuse, Epidemiol Res Branch, Div Epidemiol Serv & Prevent Res, 6001 Executive Blvd,Suite 5153 MSC 9589, Bethesda, MD 20892 USA. EM Wideroff@nih.gov RI Hernandez, Jessica/G-6527-2011; OI Piper, Margaret/0000-0002-6231-9653 FU NCI [263-MQ-610769, 263-MQ-612315, 263-MQ-612317, 263MQ-700870, 263-MQ-701381, 263-MQ612321, 263-MQ-611969, 263-MQ-612316, 263-MQ-612323, 263-MQ-611964, 263MQ-612324, 263-MQ-611967]; [HHSN261200700005C] FX The study was funded by the NCI (263-MQ-610769 to K. A. P.; 263-MQ-612315 to K. A.; 263-MQ-612317 to C. L. B.; 263MQ-700870 to M. S. D.; 263-MQ-701381 to M. F.; 263-MQ612321 to S. J. G.; 263-MQ-611969 to R. A. H.; 263-MQ-612316 to H. L. M.; 263-MQ-612323 to I. P.; 263-MQ-611964 to D. S.; 263MQ-612324 to K. A. S.; 263-MQ-611967 to the University of York; HHSN261200700005C to Scientific Consulting Group for organizational and editorial assistance). NR 83 TC 12 Z9 12 U1 2 U2 2 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 1662-4246 J9 PUBLIC HEALTH GENOMI JI Pub. Health Genomics PY 2009 VL 12 IS 4 BP 233 EP 244 DI 10.1159/000203779 PG 12 WC Genetics & Heredity; Public, Environmental & Occupational Health SC Genetics & Heredity; Public, Environmental & Occupational Health GA 432LX UT WOS:000265136600004 PM 19367091 ER PT J AU Newport, MJ Rotimi, CN AF Newport, Melanie J. Rotimi, Charles N. TI Reducing the Global Genomic Inequity Gap: Development of an African Genome Project SO PUBLIC HEALTH GENOMICS LA English DT Article C1 [Newport, Melanie J.] Brighton & Sussex Med Sch, Dept Med, Brighton BN1 9PS, E Sussex, England. [Rotimi, Charles N.] NHGRI, Ctr Res Genom & Global Hlth, NIH, Bethesda, MD 20892 USA. RP Newport, MJ (reprint author), Brighton & Sussex Med Sch, Dept Med, Brighton BN1 9PS, E Sussex, England. EM M.J.Newport@bsms.ac.uk NR 1 TC 6 Z9 6 U1 0 U2 0 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 1662-4246 J9 PUBLIC HEALTH GENOMI JI Pub. Health Genomics PY 2009 VL 12 IS 4 BP 251 EP 252 DI 10.1159/000197973 PG 2 WC Genetics & Heredity; Public, Environmental & Occupational Health SC Genetics & Heredity; Public, Environmental & Occupational Health GA 432LX UT WOS:000265136600006 PM 19182477 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 An Historical Antecedent of Modern Guidelines for Community Pandemic influenza Mitigation SO PUBLIC HEALTH REPORTS LA English DT Editorial Material ID US CITIES; INTERVENTIONS 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,Room 7A-10,31 Ctr Dr,MSC 2520, Bethesda, MD 20892 USA. EM dmorens@niaid.nih.gov FU Intramural NIH HHS [Z99 AI999999] NR 17 TC 3 Z9 3 U1 0 U2 0 PU ASSOC SCHOOLS PUBLIC HEALTH PI WASHINGTON PA 1101 15TH ST NW, STE 910, WASHINGTON, DC 20005 USA SN 0033-3549 J9 PUBLIC HEALTH REP JI Public Health Rep. PD JAN-FEB PY 2009 VL 124 IS 1 BP 22 EP 25 PG 4 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 385NI UT WOS:000261820500006 PM 19413024 ER PT J AU Sigurdson, AJ Land, CE Bhatti, P Pineda, M Brenner, A Carr, Z Gusev, BI Zhumadilov, Z Simon, SL Bouville, A Rutter, JL Ron, E Struewing, JP AF Sigurdson, Alice J. Land, Charles E. Bhatti, Parveen Pineda, Marbin Brenner, Alina Carr, Zhanat Gusev, Boris I. Zhumadilov, Zhaxibay Simon, Steven L. Bouville, Andre Rutter, Joni L. Ron, Elaine Struewing, Jeffery P. TI Thyroid Nodules, Polymorphic Variants in DNA Repair and RET-Related Genes, and Interaction with Ionizing Radiation Exposure from Nuclear Tests in Kazakhstan SO RADIATION RESEARCH LA English DT Article ID DEGREE RELATIVES; POOLED ANALYSIS; CANCER; RISK; HAPLOTYPES; CARCINOMA; DISEASES; ASSOCIATION; MECHANISMS; MUTATIONS AB Risk factors for thyroid cancer remain largely unknown except for ionizing radiation exposure during childhood and a history of benign thyroid nodules. Because thyroid nodules are more common than thyroid cancers and are associated with thyroid cancer risk, we evaluated several polymorphisms potentially relevant to thyroid tumors and assessed interaction with ionizing radiation exposure to the thyroid gland. Thyroid nodules were detected in 1998 by ultrasound screening of 2997 persons who lived near the Semipalatinsk nuclear test site in Kazakhstan when they were children (1949-1962). Cases with thyroid nodules (n = 907) were frequency matched (1:1) to those without nodules by ethnicity (Kazakh or Russian), gender and age at screening. Thyroid gland radiation doses were estimated from fallout deposition patterns, residence history and diet. We analyzed 23 polymorphisms in 13 genes and assessed interaction with ionizing radiation exposure using likelihood ratio tests (LRT). Elevated thyroid nodule risks were associated with the minor alleles of RET S836S (rs1800862, P = 0.03) and GFRA1 -193C>G (rs not assigned, P = 0.05) and decreased risk with XRCC1 R194W (rs1799782, P trend = 0.03) and TGFB1 T263I (rs1800472, P = 0.009). Similar patterns of association were observed for a small number of papillary thyroid cancers (n = 25). Ionizing radiation exposure to the thyroid gland was associated with significantly increased risk of thyroid nodules (age and gender adjusted excess odds ratio/Gy = 0.30, 95% CI 0.05-0.56), with evidence for interaction by genotype found for XRCC1 R194W (LRT P value = 0.02). Polymorphisms in RET signaling, DNA repair and proliferation genes may be related to risk of thyroid nodules, consistent with some previous reports on thyroid cancer. Borderline support for gene-radiation interaction was found for a variant in XRCC1, a key base excision repair protein. Other pathways such as genes in double-strand break repair, apoptosis and genes related to proliferation should also be pursued. (C) 2009 by Radiation Research Society C1 [Sigurdson, Alice J.; Land, Charles E.; Bhatti, Parveen; Brenner, Alina; Carr, Zhanat; Simon, Steven L.; Bouville, Andre; Ron, Elaine] NCI, Radiat Epidemiol Branch, Div Canc Epidemiol & Genet, NIH,DHHS, Bethesda, MD 20892 USA. [Pineda, Marbin; Rutter, Joni L.; Struewing, Jeffery P.] NCI, Lab Populat Genet, NIH, DHHS, Bethesda, MD 20892 USA. [Gusev, Boris I.] Kazakhstan State Res Inst Radiat Med & Ecol, Semipalatinsk, Kazakhstan. [Zhumadilov, Zhaxibay] Semipalatinsk State Med Acad, Semipalatinsk, Kazakhstan. RP Sigurdson, AJ (reprint author), NCI, Radiat Epidemiol Branch, Div Canc Epidemiol & Genet, NIH,DHHS, 6120 Execut Blvd,EPS 7060,MSC 7238, Bethesda, MD 20892 USA. EM sigurdsa@mail.nih.gov RI Struewing, Jeffery/I-7502-2013; OI Struewing, Jeffery/0000-0002-4848-3334; Rutter, Joni/0000-0002-6502-2361 FU Division of Cancer Epidemiology and Genetics of the National Cancer Institute, National Institutes of Health, Department of Health and Human Services; Harkin Award FX We are very grateful to the residents of the Kazakhstan villages who participated in this study. This study was supported in part by the Intramural Research Program of the Division of Cancer Epidemiology and Genetics of the National Cancer Institute, National Institutes of Health, Department of Health and Human Services and by the Harkin Award for research on thyroid cancer. NR 35 TC 23 Z9 25 U1 1 U2 6 PU RADIATION RESEARCH SOC PI LAWRENCE PA 810 E TENTH STREET, LAWRENCE, KS 66044 USA SN 0033-7587 J9 RADIAT RES JI Radiat. Res. PD JAN PY 2009 VL 171 IS 1 BP 77 EP 88 DI 10.1667/RR1327.1 PG 12 WC Biology; Biophysics; Radiology, Nuclear Medicine & Medical Imaging SC Life Sciences & Biomedicine - Other Topics; Biophysics; Radiology, Nuclear Medicine & Medical Imaging GA 390TX UT WOS:000262187700008 PM 19138047 ER PT J AU Weinberger, D Berger, G AF Weinberger, Daniel Berger, Gregor BE Jackson, HJ McGorry, PD TI Genetic vulnerability SO RECOGNITION AND MANAGEMENT OF EARLY PSYCHOSIS: A PREVENTIVE APPROACH, 2ND EDITION LA English DT Article; Book Chapter ID CATECHOL-O-METHYLTRANSFERASE; NEUROTROPHIC FACTOR GENE; CHILDHOOD-ONSET SCHIZOPHRENIA; VAL(108/158) MET GENOTYPE; FACTOR BDNF GENE; BIPOLAR DISORDER; SUSCEPTIBILITY GENE; ALZHEIMERS-DISEASE; PREFRONTAL CORTEX; MONOZYGOTIC TWINS C1 [Weinberger, Daniel] NIMH, Genes Cognit & Psychosis Program, NIH, Bethesda, MD 20892 USA. [Berger, Gregor] Univ Basel Hosp, Dept Psychiat, CH-4031 Basel, Switzerland. [Berger, Gregor] Schlossli Clin, Zurich, Switzerland. [Berger, Gregor] Univ Melbourne, Parkville, Vic 3052, Australia. RP Weinberger, D (reprint author), NIMH, Genes Cognit & Psychosis Program, NIH, Bethesda, MD 20892 USA. NR 140 TC 0 Z9 0 U1 1 U2 1 PU CAMBRIDGE UNIV PRESS PI CAMBRIDGE PA THE PITT BUILDING, TRUMPINGTON ST, CAMBRIDGE CB2 1RP, CAMBS, ENGLAND BN 978-0-521-61731-4 PY 2009 BP 31 EP 46 DI 10.1017/CBO9780511576287.004 D2 10.1017/CBO9780511576287 PG 16 WC Psychology, Clinical; Psychiatry; Psychology SC Psychology; Psychiatry GA BDR82 UT WOS:000314590300004 ER PT S AU Ogawa, M Kosaka, N Urano, Y Choyke, PL Kobayashi, H AF Ogawa, Mikako Kosaka, Nobuyuki Urano, Yasuteru Choyke, Peter L. Kobayashi, Hisataka BE Achilefu, S Raghavachari, R TI Activatable optical imaging probes with various fluorophore-quencher combinations SO REPORTERS, MARKERS, DYES, NANOPARTICLES, AND MOLECULAR PROBES FOR BIOMEDICAL APPLICATIONS SE Proceedings of SPIE-The International Society for Optical Engineering LA English DT Proceedings Paper CT Conference on Reporters, Markers, Dyes, Nanoparticles, and Molecular Probes for Biomedical Applications CY JAN 26-29, 2009 CL San Jose, CA SP SPIE DE molecular imaging; cancer; activatable probe; fluorophore-quencher pair ID FLUORESCENCE PROBE; CANCER; CONJUGATE; DIMERS; FRET AB Molecular imaging probes rely on high target-to-background ratios (TBR) to achieve maximum sensitivity and specificity. We utilized "quenchers" to turn off the background signal from the unbound probe and investigated the ability of specific fluorophore-quencher pairs to activate at target tissues. Both fluorophore and quencher were conjugated to a single cancer targeting molecule, either avidin or antibody. Fluorescence signal from these targeting molecules was "turned off" by the quencher in the unbound state, but was "turned on" only when the molecules bound to the cell surface target and was internalized. We tested the following fluorophore-quencher combinations based on fluorescence resonance energy transfer (FRET) pairs; OregonG-BHQ1, RhodG-BHQ1/ATTO540Q, TAMRA-QSY7/QSY21, TexRed-QSY21, Alexa647-QSY21, Cy5.5-QSY21/BHQ3 and Alexa680-QSY21/BHQ3. Among these, only RhodG-ATTO540Q and TAMRA-QSY7/21 pair showed activation upon cell binding/internalization. Among these combinations, TAMRA-QSY7 pair showed the highest activation (40-fold and 13-fold for avidin and antibody conjugate, respectively) as measured with an in vitro dissociation assay. The activation was dependent on the method used to conjugate fluorophores and quenchers to the targeting molecule. In vitro microscopic studies with TAMRA-QSY7 pair conjugated to avidin or antibody showed high fluorescent signal inside the target cancer cells, indicating activation after internalization. In vivo imaging studies in tumor bearing mice demonstrated that tumors could be clearly detected with low background. Although the precise quenching mechanism remains to be determined, this activation system can achieve high TBR in vivo molecular imaging. C1 [Ogawa, Mikako; Kosaka, Nobuyuki; Choyke, Peter L.; Kobayashi, Hisataka] NCI, Mol Imaging Program, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. RP Ogawa, M (reprint author), NCI, Mol Imaging Program, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. NR 13 TC 0 Z9 0 U1 0 U2 3 PU SPIE-INT SOC OPTICAL ENGINEERING PI BELLINGHAM PA 1000 20TH ST, PO BOX 10, BELLINGHAM, WA 98227-0010 USA SN 0277-786X BN 978-0-8194-7436-0 J9 P SOC PHOTO-OPT INS PY 2009 VL 7190 AR 71900Z DI 10.1117/12.808326 PG 8 WC Biophysics; Engineering, Biomedical; Nanoscience & Nanotechnology; Optics SC Biophysics; Engineering; Science & Technology - Other Topics; Optics GA BSS51 UT WOS:000285710200018 ER PT J AU O'Brien, SJ AF O'Brien, Stephen J. TI Comparative genomics in vertebrates: a role for the platypus SO REPRODUCTION FERTILITY AND DEVELOPMENT LA English DT Editorial Material ID SEX-CHROMOSOMES; EVOLUTION C1 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 NR 16 TC 0 Z9 0 U1 0 U2 1 PU CSIRO PUBLISHING PI COLLINGWOOD PA 150 OXFORD ST, PO BOX 1139, COLLINGWOOD, VICTORIA 3066, AUSTRALIA SN 1031-3613 J9 REPROD FERT DEVELOP JI Reprod. Fertil. Dev. PY 2009 VL 21 IS 8 BP VII EP IX DI 10.1071/RDv21n8_IN PG 3 WC Developmental Biology; Reproductive Biology; Zoology SC Developmental Biology; Reproductive Biology; Zoology GA 512KH UT WOS:000271247100002 PM 20092045 ER PT B AU Martensen, R AF Martensen, Robert BE Campbell, L Wiesen, A TI Landscape Designers, Doctors, and the Making of Healthy Urban Spaces in 19th Century America SO RESTORATIVE COMMONS: CREATING HEALTH AND WELL-BEING THROUGH URBAN LANDSCAPES SE USDA Forest Service Northern Research Station General Technical Report GTR-NRS LA English DT Proceedings Paper CT Meristem 2007 Forum CY 2007 CL New York Acad Med, New York, NY SP Harvard-Loeb Fellowship Forum, PC Landscape Architecture, Inst Landscape Studies, Terrapin Bright Green, David Kamp FASLA, LF Dirtworks HO New York Acad Med C1 [Martensen, Robert] NIH, Off NIH Hist & Museum, Bethesda, MD USA. NR 8 TC 0 Z9 0 U1 0 U2 1 PU USDA FOREST SERVICE PI NEWTOWN SQUARE PA 11 CAMPUS BLVD, STE 200, NEWTOWN SQUARE, PA 19073-3294 USA J9 USDA FOR SERV NRS GT PY 2009 IS P-39 BP 27 EP 37 PG 11 WC Horticulture; Public, Environmental & Occupational Health; Urban Studies SC Agriculture; Public, Environmental & Occupational Health; Urban Studies GA BJI17 UT WOS:000266060700001 ER PT J AU Chen, J Tsai, SY Vazin, T Coggiano, M Freed, WJ AF Chen, Jia Tsai, Shang-Yi Vazin, Tandis Coggiano, Mark Freed, William J. TI Human embryonic stem cells which express hrGFP in the undifferentiated state and during dopaminergic differentiation SO RESTORATIVE NEUROLOGY AND NEUROSCIENCE LA English DT Article DE Human embryonic stem cells; EF1-hrGFP reporter gene; nucleofection; BGO1V2-EFG; histone deacetylase; neural differentiation; dopaminergic ID TYROSINE-HYDROXYLASE; HISTONE DEACETYLASE; NEURAL PRECURSORS; GENE-EXPRESSION; PROMOTER; NEURONS; LINE; BUTYRATE; INHIBITORS; CULTURE AB Purpose: human embryonic stem cells (hESCs) which express a reporter gene consistently during all phases of differentiation would be valuable for basic research on cell transplantation. In this study, we describe karyotypically-abnormal variant hESCs, BGO1V2-EFG, which express hrGFP driven by the EF1 promoter. Methods: BGO1V2-EFG cells were analyzed by using immunocytochemistry, single cell-based confocal image, and in vitro differentiation, including dopaminergic differentiation. Results: Undifferentiated BGO1V2-EFG cells expressed pluripotent ESC markers and retained the ability to differentiate into cell types of all three germ layers. BGO1V2-EFG cells maintained stable and robust hrGFP expression in vitro in the undifferentiated state and during differentiation. The EF1 promoter retained activity during dopaminergic differentiation, as 76% of tyrosine hydroxlase (TH)-positive cells co-expressed hrGFP by confocal analysis. Treated with sodium butyrate (0.02 mM to 2.0 mM), an inhibitor of histone deacetylase (HDAC), during differentiation did not affect hrGFP expression, although TH expression was reduced by higher concentrations of sodium butyrate. Conclusion: BGO1V2-EFG cells maintain stable and robust hrGFP expression in the undifferentiated state and during neural differentiation. Especially, the EF1 promoter was effective in driving hrGFP expression during dopaminergic differentiation. BGO1V2-EFG cells may be useful for transplantation studies in Parkinson disease animal models. C1 [Chen, Jia; Tsai, Shang-Yi; Vazin, Tandis; Coggiano, Mark; Freed, William J.] NIDA, Cellular Neurobiol Res Branch, Intramural Res Program, NIH,Dept Hlth & Human Serv, Baltimore, MD 21224 USA. RP Chen, J (reprint author), NIDA, Cellular Neurobiol Res Branch, Intramural Res Program, NIH,Dept Hlth & Human Serv, 333 Cassell Dr,Triad Bldg,Room 3505, Baltimore, MD 21224 USA. EM jichen@mail.nih.gov FU NIDA; NIH; DHHS FX Research was supported by the IRP of NIDA, NIH, DHHS. NR 30 TC 6 Z9 9 U1 0 U2 5 PU IOS PRESS PI AMSTERDAM PA NIEUWE HEMWEG 6B, 1013 BG AMSTERDAM, NETHERLANDS SN 0922-6028 J9 RESTOR NEUROL NEUROS JI Restor. Neurol. Neurosci. PY 2009 VL 27 IS 4 BP 359 EP 370 DI 10.3233/RNN-2009-0521 PG 12 WC Neurosciences SC Neurosciences & Neurology GA 492BS UT WOS:000269629700010 PM 19738328 ER PT J AU Aboud, S Mhalu, F Bakari, M Lifson, J Lyamuya, E Marovich, M Cox, J Sandstrom, E Biberfeld, G Nilsson, C AF Aboud, S. Mhalu, F. Bakari, M. Lifson, J. Lyamuya, E. Marovich, M. Cox, J. Sandstrom, E. Biberfeld, G. Nilsson, C. TI HIV-specific T-lymphocyte proliferative responses induced by a multigene multiclade HIV-1 DNA/MVA heterologous vaccine in Tanzanian volunteers SO RETROVIROLOGY LA English DT Meeting Abstract C1 [Aboud, S.; Mhalu, F.; Bakari, M.; Lyamuya, E.] Muhimbili Univ Hlth & Allied Sci, Dept Microbiol & Immunol, Dar Es Salaam, Tanzania. [Lifson, J.] NCI, SAIC Frederick Inc, Frederick, MD 21701 USA. [Marovich, M.; Cox, J.] US Mil HIV Res Program, Rockville, MD USA. [Sandstrom, E.] Karolinska Univ Hosp, Stockholm, Sweden. [Biberfeld, G.] Swedish Inst Infect Dis Control, Stockholm, Sweden. [Biberfeld, G.] Karolinska Inst, Stockholm, Sweden. [Nilsson, C.] Swedish Inst Infect Dis Control SMI, Stockholm, Sweden. NR 0 TC 0 Z9 0 U1 0 U2 1 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1742-4690 J9 RETROVIROLOGY JI Retrovirology PY 2009 VL 6 AR P191 PG 1 WC Virology SC Virology GA 509KL UT WOS:000271015300242 ER PT J AU Allen, MA Gray, G Churchyard, G Bekker, L Nchabeleng, M Mlisana, K Metch, B Moodie, Z Roux, S Mathebula, M Bennie, T Kublin, J AF Allen, M. A. Gray, G. Churchyard, G. Bekker, L. Nchabeleng, M. Mlisana, K. Metch, B. Moodie, Z. Roux, S. Mathebula, M. Bennie, T. Kublin, J. TI Social impact events in Phambili, the first phase 2B HIV vaccine trial in South Africa SO RETROVIROLOGY LA English DT Meeting Abstract C1 [Allen, M. A.] NIAID, DAIDS VRP, NIH, Bethesda, MD 20892 USA. [Gray, G.] Perinatal HIV Res Unit, Soweto, South Africa. [Gray, G.] Univ Witwatersrand, Soweto, South Africa. [Churchyard, G.] Univ Cape Town, Klerksdorp, South Africa. [Bekker, L.; Roux, S.] Desmond Tutu HIV Ctr, Cape Town, South Africa. [Allen, M. A.; Nchabeleng, M.; Mathebula, M.] MeCRU, Medunsa, South Africa. [Mlisana, K.; Bennie, T.] Ctr AIDS Programme Res S Africa CAPRISA, Durban, South Africa. [Metch, B.; Moodie, Z.] Stat Ctr HIV AIDS Res & Prevent, FHCRC, Seattle, WA USA. [Kublin, J.] Fred Hutchinson Canc Res Ctr, HIV Vaccine Trials Network, Seattle, WA 98104 USA. [Churchyard, G.] Aurum Inst Hlth Res, Klerksdorp, South Africa. OI Allen, Mary/0000-0001-8163-0714 NR 0 TC 0 Z9 0 U1 0 U2 1 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1742-4690 J9 RETROVIROLOGY JI Retrovirology PY 2009 VL 6 AR P190 PG 2 WC Virology SC Virology GA 509KL UT WOS:000271015300241 ER PT J AU Bachu, M Murali, RV Babu, AMHKH Yedavalli, VSRK Jeang, KT Ranga, U AF Bachu, Mahesh Murali, Rajesh V. Babu, Anil M. H. K. H. Yedavalli, Venkat S. R. K. Jeang, Kuan-Teh Ranga, Udaykumar TI Fourth NF-kappa B site in HIV-1 subtype-C LTR confers functional advantage to viral gene expression SO RETROVIROLOGY LA English DT Meeting Abstract C1 [Bachu, Mahesh; Murali, Rajesh V.; Babu, Anil M. H. K. H.; Ranga, Udaykumar] Jawaharlal Nehru Ctr Adv Sci Res, Mol Virol Lab, Mol Biol & Genet Unit, Bangalore, Karnataka, India. [Yedavalli, Venkat S. R. K.; Jeang, Kuan-Teh] NIAID, Mol Virol Sect, Mol Microbiol Lab, NIH, Bethesda, MD 20892 USA. RI Jeang, Kuan-Teh/A-2424-2008 NR 0 TC 0 Z9 0 U1 0 U2 0 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1742-4690 J9 RETROVIROLOGY JI Retrovirology PY 2009 VL 6 AR P3 PG 1 WC Virology SC Virology GA 498MX UT WOS:000270146200055 ER PT J AU Bakari, M Aboud, S Nilsson, C Francis, J Buma, D Moshiro, C Aris, EA Lyamuya, E Janabi, M Mbwana, J Mwanyika, L Stout, R Hejdeman, B Brave, A Robb, M Marovich, M Michael, N Earl, P Moss, B Wahren, B Biberfeld, G Pallangyo, K Mhalu, F Sandstrom, E AF Bakari, M. Aboud, S. Nilsson, C. Francis, J. Buma, D. Moshiro, C. Aris, E. A. Lyamuya, E. Janabi, M. Mbwana, J. Mwanyika, L. Stout, R. Hejdeman, B. Brave, A. Robb, M. Marovich, M. Michael, N. Earl, P. Moss, B. Wahren, B. Biberfeld, G. Pallangyo, K. Mhalu, F. Sandstrom, E. TI A low dose of multigene, multiclade HIV DNA given intradermally induces strong and broad immune responses after boosting with heterologous HIV MVA SO RETROVIROLOGY LA English DT Meeting Abstract C1 [Bakari, M.; Aboud, S.; Francis, J.; Moshiro, C.; Lyamuya, E.; Mbwana, J.; Pallangyo, K.; Mhalu, F.] MUHAS, Dar Es Salaam, 20892, Tanzania. [Nilsson, C.; Brave, A.; Wahren, B.; Biberfeld, G.] Swedish Inst Infect Dis Control, Stockholm, Sweden. [Nilsson, C.; Brave, A.; Wahren, B.; Biberfeld, G.] Karolinska Inst, Stockholm, Sweden. [Buma, D.; Aris, E. A.; Janabi, M.] Muhimbili Natl Hosp, Dar Es Salaam, Tanzania. [Mwanyika, L.] Tanzania Police Force, Dar Es Salaam, Tanzania. [Hejdeman, B.; Sandstrom, E.] Soder Sjukhuset, KI, Stockholm, Sweden. [Robb, M.; Marovich, M.; Michael, N.] Walter Reed Army Inst Res, Rockville, MD USA. [Earl, P.; Moss, B.] NIAID, NIH, Bethesda, MD USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1742-4690 J9 RETROVIROLOGY JI Retrovirology PY 2009 VL 6 AR P403 PG 1 WC Virology SC Virology GA 509KL UT WOS:000271015300454 ER PT J AU Bar, KJ Keele, BF Decker, J McLellan, J Salazar-Gonzales, J Salazar, M Li, H Wang, S Yang, Y Hahn, BH Kwong, PD Shaw, GM AF Bar, K. J. Keele, B. F. Decker, J. McLellan, J. Salazar-Gonzales, J. Salazar, M. Li, H. Wang, S. Yang, Y. Hahn, B. H. Kwong, P. D. Shaw, G. M. TI Neutralizing antibody responses against conformational envelope epitopes in early HIV-1 infection SO RETROVIROLOGY LA English DT Meeting Abstract C1 [Bar, K. J.; Decker, J.; Salazar-Gonzales, J.; Salazar, M.; Li, H.; Wang, S.; Hahn, B. H.; Shaw, G. M.] Univ Alabama, Birmingham, AL USA. [Keele, B. F.] NCI, Frederick, MD 21701 USA. [McLellan, J.; Yang, Y.; Kwong, P. D.] NIH, Bethesda, MD 20892 USA. RI McLellan, Jason/A-6874-2010 NR 0 TC 1 Z9 1 U1 0 U2 0 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1742-4690 J9 RETROVIROLOGY JI Retrovirology PY 2009 VL 6 AR P71 PG 1 WC Virology SC Virology GA 509KL UT WOS:000271015300123 ER PT J AU Bar, KJ Li, H Keele, B Grayson, T Sun, R Chamberland, A Tremblay, C Markowitz, M Schumacher, J Hahn, B Shaw, G AF Bar, K. J. Li, H. Keele, B. Grayson, T. Sun, R. Chamberland, A. Tremblay, C. Markowitz, M. Schumacher, J. Hahn, B. Shaw, G. TI Multiplicity of infection by HIV-1 in injection drug users, men who have sex with men and heterosexuals SO RETROVIROLOGY LA English DT Meeting Abstract C1 [Bar, K. J.; Li, H.; Grayson, T.; Sun, R.; Schumacher, J.; Hahn, B.; Shaw, G.] Univ Alabama, Birmingham, AL USA. [Keele, B.] NCI, Frederick, MD 21701 USA. [Chamberland, A.; Tremblay, C.] Univ Montreal, Montreal, PQ, Canada. [Markowitz, M.] Aaron Diamond AIDS Res Ctr, New York, NY USA. NR 0 TC 0 Z9 0 U1 0 U2 2 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1742-4690 J9 RETROVIROLOGY JI Retrovirology PY 2009 VL 6 AR O37 PG 1 WC Virology SC Virology GA 509KL UT WOS:000271015300038 ER PT J AU Casazza, JP Bowman, K Adzaku, S Ambrozak, DA Roederer, M Bailer, RT Enama, M Nason, M Ledgerwood, JE Graham, BS Koup, RA AF Casazza, J. P. Bowman, K. Adzaku, S. Ambrozak, D. A. Roederer, M. Bailer, R. T. Enama, M. Nason, M. Ledgerwood, J. E. Graham, B. S. Koup, R. A. TI Increased HIV-specific immunity in HIV-infected individuals vaccinated with a DNA prime, rAd5 boost regimen SO RETROVIROLOGY LA English DT Meeting Abstract C1 [Casazza, J. P.; Bowman, K.; Adzaku, S.; Ambrozak, D. A.; Roederer, M.; Bailer, R. T.; Enama, M.; Nason, M.; Ledgerwood, J. E.; Graham, B. S.; Koup, R. A.] NIAID, Vaccine Res Ctr, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1742-4690 J9 RETROVIROLOGY JI Retrovirology PY 2009 VL 6 AR P315 PG 1 WC Virology SC Virology GA 509KL UT WOS:000271015300366 ER PT J AU Chang, J Kulkarni, S Meier, A Lindsay, RJ Bazner, S Lifson, JD Bosch, RJ Carrington, M Altfeld, M AF Chang, J. Kulkarni, S. Meier, A. Lindsay, R. J. Bazner, S. Lifson, J. D. Bosch, R. J. Carrington, M. Altfeld, M. TI TLR-mediated pDC responses to HIV-1 ligands SO RETROVIROLOGY LA English DT Meeting Abstract C1 [Chang, J.; Meier, A.; Lindsay, R. J.; Bazner, S.; Altfeld, M.] MIT & Harvard, Ragon Inst MGH, Boston, MA USA. [Kulkarni, S.; Carrington, M.] NCI, SAIC Frederick, Lab Genom Divers, Frederick, MD 21701 USA. [Lifson, J. D.] NCI, SAIC Frederick, AIDS & Canc Virus Program, Frederick, MD 21701 USA. [Bosch, R. J.] Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1742-4690 J9 RETROVIROLOGY JI Retrovirology PY 2009 VL 6 AR O11 PG 1 WC Virology SC Virology GA 509KL UT WOS:000271015300012 ER PT J AU Chattopadhyay, PK Brodie, T Ganesan, A Mascola, JR Michael, NL Roederer, M AF Chattopadhyay, P. K. Brodie, T. Ganesan, A. Mascola, J. R. Michael, N. L. Roederer, M. TI The first year: early correlates of long-term HIV progression SO RETROVIROLOGY LA English DT Meeting Abstract C1 [Chattopadhyay, P. K.; Mascola, J. R.; Roederer, M.] NIH, ImmunoTechnol Sect, Vaccine Res Ctr, Bethesda, MD 20892 USA. [Brodie, T.] Inst Biomed Res, Bellinzona, Switzerland. [Ganesan, A.] Natl Naval Med Ctr, Bethesda, MD USA. [Michael, N. L.] US Mil HIV Res Program, Rockville, MD USA. RI Chattopadhyay, Pratip/B-9227-2008; OI Chattopadhyay, Pratip/0000-0002-5457-9666 NR 0 TC 0 Z9 0 U1 0 U2 0 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1742-4690 J9 RETROVIROLOGY JI Retrovirology PY 2009 VL 6 AR P257 PG 2 WC Virology SC Virology GA 509KL UT WOS:000271015300308 ER PT J AU Chen, W Xiao, X Streaker, E Wang, Y Markowitz, M Haynes, B AF Chen, W. Xiao, X. Streaker, E. Wang, Y. Markowitz, M. Haynes, B. TI Monoclonal antibodies from patient with acute HIV-1 infection SO RETROVIROLOGY LA English DT Meeting Abstract C1 [Chen, W.; Xiao, X.; Streaker, E.; Wang, Y.] NCI, CCRNP, NIH, Frederick, MD 21701 USA. [Markowitz, M.] Rockefeller Univ, Aaron Diamond AIDS Res Center, New York, NY 10021 USA. [Haynes, B.] Human Vaccine Inst, Durham, NC USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1742-4690 J9 RETROVIROLOGY JI Retrovirology PY 2009 VL 6 AR P36 PG 1 WC Virology SC Virology GA 509KL UT WOS:000271015300089 ER PT J AU Cherkasova, E Lerman, MI Childs, R AF Cherkasova, Elena Lerman, Michael I. Childs, Richard TI Transcriptional regulation of HERV-E expression in clear cell renal carcinoma SO RETROVIROLOGY LA English DT Meeting Abstract C1 [Cherkasova, Elena; Lerman, Michael I.; Childs, Richard] NHLBI, NIH, Bethesda, MD 20892 USA. NR 1 TC 0 Z9 0 U1 0 U2 0 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1742-4690 J9 RETROVIROLOGY JI Retrovirology PY 2009 VL 6 AR P23 PG 1 WC Virology SC Virology GA 498MX UT WOS:000270146200075 ER PT J AU Cicala, C Martinelli, E Mcnally, JP Pascucio, M Patel, N Jelicic, K Wei, D Van Ryk, D Fauci, AS Arthos, J AF Cicala, C. Martinelli, E. Mcnally, J. P. Pascucio, M. Patel, N. Jelicic, K. Wei, D. Van Ryk, D. Fauci, A. S. Arthos, J. TI The gut mucosal homing receptor integrin alpha 4 beta 7 forms a complex with CD4 and defines a T cell subset that is highly susceptible to infection by HIV-1 SO RETROVIROLOGY LA English DT Meeting Abstract C1 [Cicala, C.; Martinelli, E.; Mcnally, J. P.; Pascucio, M.; Patel, N.; Jelicic, K.; Wei, D.; Van Ryk, D.; Fauci, A. S.; Arthos, J.] Natl Inst Allergy & Infect Dis USA, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1742-4690 J9 RETROVIROLOGY JI Retrovirology PY 2009 VL 6 AR P99 PG 1 WC Virology SC Virology GA 509KL UT WOS:000271015300151 ER PT J AU Currier, JR De Souza, M Ratto-Kim, S Paris, R Nguay, V Cox, J Earl, P Moss, B Sriplienchan, S Thongcharoen, P Kim, J Robb, M Michael, N Marovich, M AF Currier, J. R. De Souza, M. Ratto-Kim, S. Paris, R. Nguay, V. Cox, J. Earl, P. Moss, B. Sriplienchan, S. Thongcharoen, P. Kim, J. Robb, M. Michael, N. Marovich, M. TI Characterization of cell-mediated immune responses generated by recombinant modified vaccinia Ankara (rMVA)-HIV-1 in a phase I vaccine trial SO RETROVIROLOGY LA English DT Meeting Abstract C1 [Currier, J. R.; Ratto-Kim, S.; Nguay, V.; Kim, J.; Robb, M.; Michael, N.; Marovich, M.] Mil HIV Res Program, Dept Vaccine Res & Dev, Rockville, MD USA. [De Souza, M.; Paris, R.; Sriplienchan, S.; Thongcharoen, P.] AFRIMS, Bangkok, Thailand. [Cox, J.] IAVI, Rockville, MD USA. [Earl, P.; Moss, B.] NIAID, Bethesda, MD 20892 USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1742-4690 J9 RETROVIROLOGY JI Retrovirology PY 2009 VL 6 AR O27 PG 1 WC Virology SC Virology GA 509KL UT WOS:000271015300028 ER PT J AU Didierlaurent, L Houzet, L Paillart, JC Morichaud, Z Smagulova, F Maurel, S Marquet, R Mougel, M AF Didierlaurent, Ludovic Houzet, Laurent Paillart, Jean-Christophe Morichaud, Zakia Smagulova, Fatima Maurel, Stephan Marquet, Roland Mougel, Marylene TI HIV-1 specifically encapsidates other nucleic acids than its genomic RNA SO RETROVIROLOGY LA English DT Meeting Abstract ID VIRIONS C1 [Didierlaurent, Ludovic; Houzet, Laurent; Morichaud, Zakia; Smagulova, Fatima; Maurel, Stephan; Mougel, Marylene] Equipe Assemblage & Replicat Retrovirus, UMII CPBS, UMI, CNRS,UMR 5236, Montpellier, France. [Houzet, Laurent] NIAID, Mol Virol Sect, Mol Microbiol Lab, NIH, Bethesda, MD 20892 USA. [Paillart, Jean-Christophe; Marquet, Roland] ULP, CNRS, UPR9002, Architecture & React ARN, Strasbourg, France. RI Paillart, Jean-Christophe/A-4171-2010; Mougel, Marylene/K-7958-2013 OI Mougel, Marylene/0000-0002-0345-1427 NR 4 TC 0 Z9 0 U1 0 U2 5 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1742-4690 J9 RETROVIROLOGY JI Retrovirology PY 2009 VL 6 AR P31 PG 1 WC Virology SC Virology GA 498MX UT WOS:000270146200083 ER PT J AU Dosenovic, P Guenaga, J Ofek, G Baker, D Schief, W Kwong, PD Hedestam, GBK Wyatt, RT AF Dosenovic, P. Guenaga, J. Ofek, G. Baker, D. Schief, W. Kwong, P. D. Hedestam, G. B. Karlsson Wyatt, R. T. TI Analysis of antibody and B cell responses following inoculation with computationally designed HIV-1 2F5 epitope scaffold proteins SO RETROVIROLOGY LA English DT Meeting Abstract C1 [Dosenovic, P.; Hedestam, G. B. Karlsson] Karolinska Inst, Dept Microbiol Tumor & Cell Biol, Stockholm, Sweden. [Guenaga, J.; Ofek, G.; Kwong, P. D.; Wyatt, R. T.] NIH, Vaccine Res Ctr, Bethesda, MD 20892 USA. [Baker, D.; Schief, W.] Univ Washington, Dept Biochem, Seattle, WA 98195 USA. RI Baker, David/K-8941-2012 OI Baker, David/0000-0001-7896-6217 NR 0 TC 0 Z9 0 U1 0 U2 1 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1742-4690 J9 RETROVIROLOGY JI Retrovirology PY 2009 VL 6 AR P178 PG 1 WC Virology SC Virology GA 509KL UT WOS:000271015300229 ER PT J AU Douagi, I Forsell, MM Sundling, C O'dell, S Seder, R Mascola, JR Lore, K Wyatt, RT AF Douagi, I. Forsell, M. M. Sundling, C. O'dell, S. Seder, R. Mascola, J. R. Lore, K. Wyatt, R. T. TI Impact of in vivo CD4 binding during HIV-1 Env trimer immunizations of rhesus macaques SO RETROVIROLOGY LA English DT Meeting Abstract C1 [Douagi, I.; Forsell, M. M.; Sundling, C.] Karolinska Inst, Dept Microbiol Tumor & Cell Biol, Stockholm, Sweden. [O'dell, S.; Seder, R.; Mascola, J. R.; Wyatt, R. T.] NIH, Vaccine Res Ctr, Bethesda, MD 20892 USA. [Lore, K.] Karolinska Inst, Ctr Infect Med, Stockholm, Sweden. NR 0 TC 0 Z9 0 U1 0 U2 1 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1742-4690 J9 RETROVIROLOGY JI Retrovirology PY 2009 VL 6 AR O35 PG 1 WC Virology SC Virology GA 509KL UT WOS:000271015300036 ER PT J AU Eller, L Ouma, B Oballah, P Eller, MA de Souza, MS Wabwire-Mangen, F Laeyendecker, O Quinn, T Kiwanuka, N Serwadda, D Sewankambo, N Wawer, M Gray, R Michael, NL Robb, ML Montefiori, D Brown, BK Polonis, VR AF Eller, L. Ouma, B. Oballah, P. Eller, M. A. de Souza, M. S. Wabwire-Mangen, F. Laeyendecker, O. Quinn, T. Kiwanuka, N. Serwadda, D. Sewankambo, N. Wawer, M. Gray, R. Michael, N. L. Robb, M. L. Montefiori, D. Brown, B. K. Polonis, V. R. TI Breadth and magnitude of neutralizing antibody responses in subjects infected with HIV-1 subtype D or recombinants in Rakai district, Uganda SO RETROVIROLOGY LA English DT Meeting Abstract C1 [Eller, L.; Eller, M. A.; Michael, N. L.; Robb, M. L.; Brown, B. K.; Polonis, V. R.] Makerere Univ, Walter Reed Project, US Mil HIV Res Program, Kampala, Uganda. [de Souza, M. S.] Armed Forces Res Inst Med Sci, Bangkok 10400, Thailand. [Wabwire-Mangen, F.; Kiwanuka, N.; Serwadda, D.] Makerere Univ, Walter Reed Makerere Univ, Sch Publ Hlth, Kampala, Uganda. [Laeyendecker, O.; Quinn, T.; Wawer, M.; Gray, R.] NIAID, Johns Hopkins Sch Med, NIH, Baltimore, MD USA. [Sewankambo, N.] Makerere Univ, Coll Hlth Sci, Kampala, Uganda. [Montefiori, D.] Duke Univ, Durham, NC USA. RI Laeyendecker, Oliver/B-9331-2009 NR 0 TC 0 Z9 0 U1 0 U2 0 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1742-4690 J9 RETROVIROLOGY JI Retrovirology PY 2009 VL 6 AR P56 PG 1 WC Virology SC Virology GA 509KL UT WOS:000271015300109 ER PT J AU Enama, ME Novik, L Holman, L Gordon, I Nason, M Ledgerwood, J Graham, BS AF Enama, M. E. Novik, L. Holman, L. Gordon, I. Nason, M. Ledgerwood, J. Graham, B. S. TI Safety and tolerability of VRC DNA and rAd5 HIV-1 vaccine delivery by intramuscular, subcutaneous and intradermal administration in healthy adults SO RETROVIROLOGY LA English DT Meeting Abstract C1 [Enama, M. E.; Novik, L.; Holman, L.; Gordon, I.; Ledgerwood, J.; Graham, B. S.] NIAID, VRC, NIH, Bethesda, MD 20892 USA. [Nason, M.] NIAID, BRB, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1742-4690 J9 RETROVIROLOGY JI Retrovirology PY 2009 VL 6 AR P200 PG 2 WC Virology SC Virology GA 509KL UT WOS:000271015300251 ER PT J AU Felber, BK Valentin, A von Gegerfelt, A Jalah, R Patel, V Kulkarni, V Alicea, C Rosati, M Khan, A Draghia-Akli, R Pavlakis, GN AF Felber, B. K. Valentin, A. von Gegerfelt, A. Jalah, R. Patel, V. Kulkarni, V. Alicea, C. Rosati, M. Khan, A. Draghia-Akli, R. Pavlakis, G. N. TI Persistent virological benefit in SIV-infected macaques upon therapeutic vaccination upon vaccination with DNA vectors SO RETROVIROLOGY LA English DT Meeting Abstract C1 [Felber, B. K.; Jalah, R.; Kulkarni, V.; Alicea, C.; Rosati, M.] NCI, Ctr Canc Res, Frederick, MD 21701 USA. [Valentin, A.; von Gegerfelt, A.; Patel, V.; Pavlakis, G. N.] NCI, HRS, VB, Frederick, MD 21701 USA. [Khan, A.; Draghia-Akli, R.] VGX Pharmaceut Inc, The Woodlands, TX USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1742-4690 J9 RETROVIROLOGY JI Retrovirology PY 2009 VL 6 AR P318 PG 2 WC Virology SC Virology GA 509KL UT WOS:000271015300369 ER PT J AU Felber, BK Kim, E Pal, R Desrosiers, RC Wolinsky, SM Pavlakis, GN AF Felber, B. K. Kim, E. Pal, R. Desrosiers, R. C. Wolinsky, S. M. Pavlakis, G. N. TI Monospecific expansion of SIVmac251 during acute infection masks multiple transmitted virus variants revealed during the chronic phase SO RETROVIROLOGY LA English DT Meeting Abstract C1 [Felber, B. K.] NCI, Canc Res Ctr, HRPS, VB, Frederick, MD 21701 USA. [Kim, E.; Wolinsky, S. M.] Northwestern Univ, Chicago, IL 60611 USA. [Desrosiers, R. C.] Harvard Univ, Sch Med, New England Reg Primate Res Ctr, Southborough, MA 01772 USA. [Pavlakis, G. N.] NCI, HRS, VB, Frederick, MD 21701 USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1742-4690 J9 RETROVIROLOGY JI Retrovirology PY 2009 VL 6 AR O38 PG 1 WC Virology SC Virology GA 509KL UT WOS:000271015300039 ER PT J AU Fischer, W Apetrei, C Hahn, BH Letvin, NL Nabel, GJ Korber, BT AF Fischer, W. Apetrei, C. Hahn, B. H. Letvin, N. L. Nabel, G. J. Korber, B. T. TI Gene-to-gene differences in evolutionary rate between HIV-1 and natural SIV from sooty mangabeys: implications for vaccine tests in non-human primates SO RETROVIROLOGY LA English DT Meeting Abstract C1 [Fischer, W.; Korber, B. T.] Los Alamos Natl Lab, Los Alamos, NM USA. [Apetrei, C.] Tulane Univ, Dept Trop Med, New Orleans, LA 70118 USA. [Hahn, B. H.] Univ Alabama, Dept Med, Birmingham, AL 35294 USA. [Letvin, N. L.] Univ Alabama, Dept Microbiol, Birmingham, AL 35294 USA. [Letvin, N. L.] Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. [Nabel, G. J.] NAID, Vaccine Res Ctr, NIH, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1742-4690 J9 RETROVIROLOGY JI Retrovirology PY 2009 VL 6 MA P425 PG 2 WC Virology SC Virology GA 509KL UT WOS:000271015300476 ER PT J AU Flatz, LR Kong, W Ko, S Roychoudhuri, R Wang, L Xu, L Yang, Z Honda, M Pinschewer, DD Nabel, GJ AF Flatz, L. R. Kong, W. Ko, S. Roychoudhuri, R. Wang, L. Xu, L. Yang, Z. Honda, M. Pinschewer, D. D. Nabel, G. J. TI Replication-defective lymphocytic choriomeningitis virus vectors boost cellular and humoral immunity after DNA or adenovirus vector priming SO RETROVIROLOGY LA English DT Meeting Abstract C1 [Flatz, L. R.; Kong, W.; Ko, S.; Roychoudhuri, R.; Wang, L.; Xu, L.; Yang, Z.; Honda, M.; Nabel, G. J.] NIAID, Vaccine Res Ctr, NIH, Bethesda, MD 20892 USA. [Pinschewer, D. D.] Univ Geneva, Dept Pathol & Immunol, CMU, Geneva, Switzerland. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1742-4690 J9 RETROVIROLOGY JI Retrovirology PY 2009 VL 6 AR P357 PG 2 WC Virology SC Virology GA 509KL UT WOS:000271015300408 ER PT J AU Franchini, G AF Franchini, G. TI Improvement of the efficacy of ALVAC-HIV vaccine candidates for humans in non human primates SO RETROVIROLOGY LA English DT Meeting Abstract C1 [Franchini, G.] NCI, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1742-4690 J9 RETROVIROLOGY JI Retrovirology PY 2009 VL 6 AR P415 PG 1 WC Virology SC Virology GA 509KL UT WOS:000271015300466 ER PT J AU Freel, SA Chattopadhyay, PK Lamoreaux, L Zarkowsky, D Overman, RG Ochsenbauer-Jambor, C Kappes, JC Cunningham, CK Denny, TN Weinhold, KJ Ferrari, G Koup, RA Graham, BS Haynes, BF Roederer, M Tomaras, GD AF Freel, S. A. Chattopadhyay, P. K. Lamoreaux, L. Zarkowsky, D. Overman, R. G. Ochsenbauer-Jambor, C. Kappes, J. C. Cunningham, C. K. Denny, T. N. Weinhold, K. J. Ferrari, G. Koup, R. A. Graham, B. S. Haynes, B. F. Roederer, M. Tomaras, G. D. TI Phenotypic analyses of CD8+T cells that mediate virus inhibition from HIV-1 vaccinees and HIV-1+virus controllers SO RETROVIROLOGY LA English DT Meeting Abstract C1 [Freel, S. A.] Duke Univ, Sch Med, DHVI & Surg, Durham, NC USA. [Chattopadhyay, P. K.; Roederer, M.] NIAID, Immunotechnol Sect, Vaccine Res Ctr, NIH, Bethesda, MD 20892 USA. [Lamoreaux, L.; Zarkowsky, D.; Koup, R. A.] NIAID, Immunol Core Sect, Vaccine Res Ctr, NIH, Bethesda, MD USA. [Overman, R. G.; Denny, T. N.; Weinhold, K. J.; Haynes, B. F.; Tomaras, G. D.] Duke Univ, Med Ctr, DHVI & Surg, Durham, NC USA. [Ochsenbauer-Jambor, C.; Kappes, J. C.] Univ Alabama, Dept Med, Birmingham, AL 35294 USA. [Cunningham, C. K.] Duke Univ, Med Ctr, Dept Pediat, Durham, NC USA. [Ferrari, G.] Duke Univ, Med Ctr, Dept Surg, Durham, NC USA. [Graham, B. S.] NIAID, Viral Pathogenesis Lab, Vaccine Res Ctr, NIH, Bethesda, MD 20892 USA. RI Chattopadhyay, Pratip/B-9227-2008; Tomaras, Georgia/J-5041-2016 NR 0 TC 0 Z9 0 U1 0 U2 0 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1742-4690 J9 RETROVIROLOGY JI Retrovirology PY 2009 VL 6 AR O1 PG 1 WC Virology SC Virology GA 509KL UT WOS:000271015300002 ER PT J AU Gray, GE Bekker, L Churchyard, G Nchabeleng, M Mlisana, K de Bruyn, G Roux, S Mathebula, M Latka, M Bennie, T Metch, B Moodie, Z Allen, M Eaton, N Kublin, J AF Gray, G. E. Bekker, L. Churchyard, G. Nchabeleng, M. Mlisana, K. de Bruyn, G. Roux, S. Mathebula, M. Latka, M. Bennie, T. Metch, B. Moodie, Z. Allen, M. Eaton, N. Kublin, J. TI Did unblinding affect HIV risk behaviour and risk perception in the HVTN503/Phambili study? SO RETROVIROLOGY LA English DT Meeting Abstract C1 [Gray, G. E.; de Bruyn, G.] Perinatal HIV Res Unit, Soweto, South Africa. [Bekker, L.; Roux, S.] Desmond Tutu HIV Fdn, Cape Town, South Africa. [Churchyard, G.; Latka, M.] Aurum Inst Hlth Res, Cape Town, South Africa. [Nchabeleng, M.; Mathebula, M.; Bennie, T.] Medunsa HIV Clin Res Unit MeCRU, Tswane, South Africa. [Mlisana, K.] CAPRISA, Durban, South Africa. [Metch, B.; Moodie, Z.] FHCRC, Stat Ctr HIV AIDS Res & Prevent, Seattle, WA USA. [Allen, M.] NIAID, NIH, Bethesda, MD 20892 USA. [Eaton, N.; Kublin, J.] Fred Hutchinson Canc Res Ctr, HIV Vaccine Trials Network, Seattle, WA 98104 USA. NR 0 TC 1 Z9 1 U1 1 U2 1 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1742-4690 J9 RETROVIROLOGY JI Retrovirology PY 2009 VL 6 AR P209 PG 1 WC Virology SC Virology GA 509KL UT WOS:000271015300260 ER PT J AU Harris, LD Estes, JD Klatt, NR Taft, B Barclay, R Douek, DC Silvestri, G Liffson, J Brenchley, J AF Harris, L. D. Estes, J. D. Klatt, N. R. Taft, B. Barclay, R. Douek, D. C. Silvestri, G. Liffson, J. Brenchley, J. TI Extensive intestinal damage underlies microbial translocation in the GI tract of chronically SIV-infected Rhesus macaques SO RETROVIROLOGY LA English DT Meeting Abstract C1 [Harris, L. D.; Klatt, N. R.; Brenchley, J.] NIAID, Immunopathogenesis Unit, Mol Microbiol Lab, NIH, Bethesda, MD 20892 USA. [Estes, J. D.; Taft, B.; Liffson, J.] NCI, AIDS & Canc Virus Program, SAIC, NIH, Frederick, MD 21701 USA. [Barclay, R.] Univ Edinburgh, Ctr Regenerat Med, Edinburgh, Midlothian, Scotland. [Douek, D. C.] NIAID, Human Immunol Sect, Vaccine Res Ctr, NIH, Bethesda, MD 20892 USA. [Silvestri, G.] Univ Penn, Dept Pathol, Philadelphia, PA 19104 USA. [Silvestri, G.] Univ Penn, Lab Med, Philadelphia, PA 19104 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1742-4690 J9 RETROVIROLOGY JI Retrovirology PY 2009 VL 6 AR P146 PG 1 WC Virology SC Virology GA 509KL UT WOS:000271015300198 ER PT J AU Hirao, LA Wu, L Khan, AS Dai, A Karl, J Lank, S Wiseman, R O'Connor, D Watkins, D Miller, N Betts, MR Sardesai, NY Boyer, JD Weiner, DB AF Hirao, L. A. Wu, L. Khan, A. S. Dai, A. Karl, J. Lank, S. Wiseman, R. O'Connor, D. Watkins, D. Miller, N. Betts, M. R. Sardesai, N. Y. Boyer, J. D. Weiner, D. B. TI DNA vaccination with IL-12 lowers viral replication following SIVmac251 challenge SO RETROVIROLOGY LA English DT Meeting Abstract C1 [Hirao, L. A.; Wu, L.; Dai, A.; Betts, M. R.; Boyer, J. D.; Weiner, D. B.] Univ Penn, Philadelphia, PA 19104 USA. [Khan, A. S.; Sardesai, N. Y.] VGX Pharmaceut, The Woodlands, TX USA. [Karl, J.; Lank, S.; Wiseman, R.; O'Connor, D.; Watkins, D.] Univ Wisconsin, Madison, WI USA. [Miller, N.] NIAID, Bethesda, MD 20892 USA. RI Weiner, David/H-8579-2014 NR 0 TC 0 Z9 0 U1 0 U2 1 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1742-4690 J9 RETROVIROLOGY JI Retrovirology PY 2009 VL 6 AR P28 PG 2 WC Virology SC Virology GA 509KL UT WOS:000271015300081 ER PT J AU Jeang, KT AF Jeang, Kuan-Teh TI Novel cellular processes that regulate post-transcriptional expression of HIV-1 transcripts SO RETROVIROLOGY LA English DT Meeting Abstract C1 [Jeang, Kuan-Teh] NIH, Bethesda, MD 20892 USA. RI Jeang, Kuan-Teh/A-2424-2008 NR 0 TC 0 Z9 0 U1 0 U2 0 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1742-4690 J9 RETROVIROLOGY JI Retrovirology PY 2009 VL 6 AR I15 PG 1 WC Virology SC Virology GA 498MX UT WOS:000270146200016 ER PT J AU Johnson, D Merino, Y Berkowitz, N Vasilenko, O Larkin, B Young, S Graham, B Ledgerwood, JM AF Johnson, D. Merino, Y. Berkowitz, N. Vasilenko, O. Larkin, B. Young, S. Graham, B. Ledgerwood, J. M. TI An evaluation of prescreen recruitment data: enrolling racial/ethnic minorities in Phase I HIV vaccine clinical trials SO RETROVIROLOGY LA English DT Meeting Abstract C1 [Johnson, D.; Merino, Y.; Berkowitz, N.; Vasilenko, O.; Larkin, B.; Young, S.; Graham, B.; Ledgerwood, J. M.] NIAID, Vaccine Res Ctr, NIH, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1742-4690 J9 RETROVIROLOGY JI Retrovirology PY 2009 VL 6 AR P406 PG 2 WC Virology SC Virology GA 509KL UT WOS:000271015300457 ER PT J AU Kannanganat, S Nigam, P Velu, V Earl, P Lai, L Lawson, B Chennareddi, L Wilson, R Kozlowski, P Moss, B Robinson, H Amara, R AF Kannanganat, S. Nigam, P. Velu, V. Earl, P. Lai, L. Lawson, B. Chennareddi, L. Wilson, R. Kozlowski, P. Moss, B. Robinson, H. Amara, R. TI Influence of preexisting vaccinia immunity on a DNA/MVA SIV vaccine, decreased cellular immunity but enhanced control of a pathogenic SIV challenge SO RETROVIROLOGY LA English DT Meeting Abstract C1 [Earl, P.; Moss, B.] NIH, Viral Dis Lab, Bethesda, MD 20892 USA. [Wilson, R.; Kozlowski, P.] Louisiana State Univ, Hlth Sci Ctr, New Orleans, LA USA. [Robinson, H.] Geovax Inc, Atlanta, GA USA. [Kannanganat, S.; Nigam, P.; Velu, V.; Lai, L.; Lawson, B.; Chennareddi, L.; Amara, R.] Emory Univ, Yerkes Natl Primate Ctr, Atlanta, GA 30322 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1742-4690 J9 RETROVIROLOGY JI Retrovirology PY 2009 VL 6 AR O51 PG 2 WC Virology SC Virology GA 509KL UT WOS:000271015300052 ER PT J AU Ko, S Wang, L Cheng, C Kong, W Gall, J King, R Nabel, GJ AF Ko, S. Wang, L. Cheng, C. Kong, W. Gall, J. King, R. Nabel, G. J. TI Development of recombinant adenovirus 28 vectors for HIV vaccines SO RETROVIROLOGY LA English DT Meeting Abstract C1 [Ko, S.; Wang, L.; Cheng, C.; Kong, W.; Nabel, G. J.] NIAID, Virol Lab, Vaccine Res Ctr, NIH, Bethesda, MD 20892 USA. [Gall, J.; King, R.] Genvec Inc, Gaithersburg, MD USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1742-4690 J9 RETROVIROLOGY JI Retrovirology PY 2009 VL 6 AR P309 PG 1 WC Virology SC Virology GA 509KL UT WOS:000271015300360 ER PT J AU Latka, M Grey, G Fielding, K Bekker, L Mlisana, K Nchabeleng, M DeBruin, G Allen, M Kublin, J Churchyard, G AF Latka, M. Grey, G. Fielding, K. Bekker, L. Mlisana, K. Nchabeleng, M. DeBruin, G. Allen, M. Kublin, J. Churchyard, G. TI Factors associated with pregnancy during the HVTN 503/Phambili trial, a phase IIB HIV trial of the Merck Ad-5 multi-clade HIV vaccine SO RETROVIROLOGY LA English DT Meeting Abstract C1 [Latka, M.; Churchyard, G.] Aurum Inst, Houghton, South Africa. [Grey, G.; DeBruin, G.] Univ Witwatersrand, Perinatal Hlth Res Unit, Johannesburg, South Africa. [Fielding, K.] London Sch Hyg & Trop Med, London WC1, England. [Bekker, L.] Desmond Tutu HIV Ctr, Cape Town, South Africa. [Mlisana, K.] CAPRISA, Durban, South Africa. [Nchabeleng, M.] MEDUNSA, Pretoria, South Africa. [Allen, M.] NIH, Washington, DC USA. [Kublin, J.] Fred Hutchinson Canc Res Ctr, Seattle, WA 98104 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1742-4690 J9 RETROVIROLOGY JI Retrovirology PY 2009 VL 6 AR P187 PG 1 WC Virology SC Virology GA 509KL UT WOS:000271015300238 ER PT J AU Lau, C Swann, EM Gaist, P Allen, MA AF Lau, C. Swann, E. M. Gaist, P. Allen, M. A. TI Behavioral and social science in HIV vaccine clinical research: workshop recommendations SO RETROVIROLOGY LA English DT Meeting Abstract C1 [Lau, C.; Swann, E. M.; Gaist, P.; Allen, M. A.] NIH, Behav & Social Sci Grp, DAIDS, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1742-4690 J9 RETROVIROLOGY JI Retrovirology PY 2009 VL 6 AR P219 PG 1 WC Virology SC Virology GA 509KL UT WOS:000271015300270 ER PT J AU Ledgerwood, JE Novik, L Enama, ME Gordon, IJ Holman, LA Nason, MC Bailer, RT Roederer, M Koup, RA Mascola, JR Nabel, GJ Graham, BS AF Ledgerwood, J. E. Novik, L. Enama, M. E. Gordon, I. J. Holman, L. A. Nason, M. C. Bailer, R. T. Roederer, M. Koup, R. A. Mascola, J. R. Nabel, G. J. Graham, B. S. TI Comparable immunogenicity of VRC DNA and rAd5 HIV-1 vaccines delivered by intramuscular, subcutaneous and intradermal routes in healthy adults (VRC 011) SO RETROVIROLOGY LA English DT Meeting Abstract C1 [Ledgerwood, J. E.; Novik, L.; Enama, M. E.; Gordon, I. J.; Holman, L. A.; Nason, M. C.; Bailer, R. T.; Roederer, M.; Koup, R. A.; Mascola, J. R.; Nabel, G. J.; Graham, B. S.] NIAID, Vaccine Res Ctr, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1742-4690 J9 RETROVIROLOGY JI Retrovirology PY 2009 VL 6 AR P198 PG 1 WC Virology SC Virology GA 509KL UT WOS:000271015300249 ER PT J AU Letvin, N Mascola, J Rao, S Buzby, A Roederer, M Hudgens, M Gilbert, P Seder, R Douek, D Koup, R Graham, B Nabel, G AF Letvin, N. Mascola, J. Rao, S. Buzby, A. Roederer, M. Hudgens, M. Gilbert, P. Seder, R. Douek, D. Koup, R. Graham, B. Nabel, G. TI Gene-based vaccination protects against mucosal infection by a heterologous highly pathogenic SIV isolate in rhesus monkeys SO RETROVIROLOGY LA English DT Meeting Abstract C1 [Letvin, N.; Buzby, A.] Harvard Univ, Sch Med, Beth Israel Deaconess Hosp, Boston, MA USA. [Mascola, J.; Rao, S.; Roederer, M.; Seder, R.; Douek, D.; Koup, R.; Graham, B.; Nabel, G.] NIAID, Vaccine Res Ctr, NIH, Bethesda, MD 20892 USA. [Hudgens, M.] Univ N Carolina, Chapel Hill, NC USA. [Gilbert, P.] Fred Hutchinson Canc Res Ctr, Seattle, WA 98104 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1742-4690 J9 RETROVIROLOGY JI Retrovirology PY 2009 VL 6 AR P421 PG 1 WC Virology SC Virology GA 509KL UT WOS:000271015300472 ER PT J AU Maenetje, PW Casazza, J Riou, C Ambrozak, D Gray, G de Bruyn, G Koup, R Gray, C AF Maenetje, P. W. Casazza, J. Riou, C. Ambrozak, D. Gray, G. de Bruyn, G. Koup, R. Gray, C. TI A less differentiated memory phenotype of Gag-specific CD4+T-cells during primary HIV infection associates with viral control at 12 months SO RETROVIROLOGY LA English DT Meeting Abstract C1 [Maenetje, P. W.; Riou, C.; Ambrozak, D.; Koup, R.; Gray, C.] Natl Inst Communicable Dis, Johannesburg, South Africa. [Casazza, J.] NIAID, Vaccine Res Ctr, NIH, Bethesda, MD 20892 USA. [Gray, G.; de Bruyn, G.] Perinatal HIV Res Unit Soweto, Johannesburg, South Africa. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1742-4690 J9 RETROVIROLOGY JI Retrovirology PY 2009 VL 6 AR O44 PG 1 WC Virology SC Virology GA 509KL UT WOS:000271015300045 ER PT J AU Malherbe, DC Doria-Rose, N Misher, L Beckett, T Blay-Puryear, W Barnett, S Srivastava, I Richardson, B Stamatatos, L Haigwood, NL AF Malherbe, D. C. Doria-Rose, N. Misher, L. Beckett, T. Blay-Puryear, W. Barnett, S. Srivastava, I. Richardson, B. Stamatatos, L. Haigwood, N. L. TI Sequential immunization with a subtype B HIV-1 envelope quasispecies elicits broader neutralization than vaccination with a single envelope clone SO RETROVIROLOGY LA English DT Meeting Abstract C1 [Malherbe, D. C.; Haigwood, N. L.] Oregon Hlth & Sci Univ, Beaverton, OR USA. [Doria-Rose, N.] NIH, Bethesda, MD 20892 USA. [Misher, L.; Beckett, T.] Trub Pharmaceut, Seattle, WA USA. [Blay-Puryear, W.] Boston Univ, Boston, MA 02215 USA. [Barnett, S.; Srivastava, I.] Novartis Vaccines & Diagnost, Cambridge, MA USA. [Richardson, B.] Univ Washington, Seattle, WA 98195 USA. [Stamatatos, L.] Seattle Biomed Res Inst, Seattle, WA 98109 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1742-4690 J9 RETROVIROLOGY JI Retrovirology PY 2009 VL 6 AR P86 PG 2 WC Virology SC Virology GA 509KL UT WOS:000271015300138 ER PT J AU Manches, O Munn, D Fallahi, A Lifson, J Chaperot, L Plumas, J Bhardwaj, N AF Manches, O. Munn, D. Fallahi, A. Lifson, J. Chaperot, L. Plumas, J. Bhardwaj, N. TI HIV-activated human plasmacytoid DCs induce Tregs through an indoleamine 2,3-dioxygenase-dependent mechanism SO RETROVIROLOGY LA English DT Meeting Abstract C1 [Manches, O.; Fallahi, A.; Bhardwaj, N.] NYU, Langone Med Ctr, Inst Canc, New York, NY USA. [Munn, D.] Med Coll Georgia, Augusta, GA 30912 USA. [Lifson, J.] NCI, Frederick, MD 21701 USA. [Chaperot, L.; Plumas, J.] EFS Rhone Alpes, INSERM, U823, La Tronche, France. RI Plumas, Joel/N-2516-2013; chaperot, laurence/N-2927-2013 NR 0 TC 0 Z9 0 U1 0 U2 0 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1742-4690 J9 RETROVIROLOGY JI Retrovirology PY 2009 VL 6 AR P281 PG 1 WC Virology SC Virology GA 509KL UT WOS:000271015300332 ER PT J AU Mariani, SA Crotti, A Vicenzi, E Huang, DW Lempicky, R Cicala, C Arthos, J Poli, G AF Mariani, Samanta A. Crotti, Andrea Vicenzi, Elisa Huang Dawei Lempicky, Richard Cicala, Claudia Arthos, James Poli, Guido TI Post-entry events of efficient R5 vs. inefficient X4 HIV-1 replication in primary CD4(+) T lymphocytes, a transcriptome analysis SO RETROVIROLOGY LA English DT Meeting Abstract C1 [Mariani, Samanta A.; Crotti, Andrea; Vicenzi, Elisa; Poli, Guido] Ist Sci San Raffaele, Dept Immunol Transplantat & Infect Dis, I-20132 Milan, Italy. [Huang Dawei; Lempicky, Richard] Sci Applicat Int Corp, Frederick, MD 21702 USA. [Cicala, Claudia; Arthos, James] NIAID, Bethesda, MD 20892 USA. NR 1 TC 0 Z9 0 U1 0 U2 1 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1742-4690 J9 RETROVIROLOGY JI Retrovirology PY 2009 VL 6 SU 2 AR I19 PG 1 WC Virology SC Virology GA 498MX UT WOS:000270146200020 ER PT J AU Mark, D Middelkoop, K Roux, S Gray, G Mlisana, K Nchabaleng, M Churchyard, G De Bruyn, G Latka, M Magagula, D Kublin, J Allen, M Bekker, L AF Mark, D. Middelkoop, K. Roux, S. Gray, G. Mlisana, K. Nchabaleng, M. Churchyard, G. De Bruyn, G. Latka, M. Magagula, D. Kublin, J. Allen, M. Bekker, L. CA T NIAID HIV Vaccine Trials Network TI HVTN 503(Phambili) trial discontinuation of enrolment/vaccination: the impact on trial participant attitudes to vaccine trials and scientific research SO RETROVIROLOGY LA English DT Meeting Abstract C1 [Mark, D.; Middelkoop, K.; Roux, S.; Bekker, L.; T NIAID HIV Vaccine Trials Network] Univ Cape Town, Desmond Tutu HIV Ctr, ZA-7925 Cape Town, South Africa. [Gray, G.; De Bruyn, G.] Univ Witwatersrand, Perinatal HIV Res Unit, Johannesburg, South Africa. [Mlisana, K.; Magagula, D.] Univ KwaZulu Natal, CAPRISA, Durban, South Africa. [Nchabaleng, M.] Univ Limpopo, Medunsa Clin Res Unit, Pretoria, South Africa. [Churchyard, G.; Latka, M.] Aurum Inst Hlth Res, Johannesburg, South Africa. [Kublin, J.] HIV Vaccine Trials Network, Seattle, WA USA. [Allen, M.] NIAID, DAIDS, NIH, Bethesda, MD 20892 USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1742-4690 J9 RETROVIROLOGY JI Retrovirology PY 2009 VL 6 AR P214 PG 1 WC Virology SC Virology GA 509KL UT WOS:000271015300265 ER PT J AU Mir, KD Milush, JM Brenchley, JM Reeves, JD Gordon, SN Else, JG O'Neill, E Silvestri, G Sodora, DL AF Mir, K. D. Milush, J. M. Brenchley, J. M. Reeves, J. D. Gordon, S. N. Else, J. G. O'Neill, E. Silvestri, G. Sodora, D. L. TI Preserved adaptive immune responses and limited immune activation in CD4-low SIV-positive sooty mangabeys SO RETROVIROLOGY LA English DT Meeting Abstract C1 [Mir, K. D.; Sodora, D. L.] Seattle Biomed Res Inst, Viral Vaccines Program, Seattle, WA 98109 USA. [Milush, J. M.] Univ Calif San Francisco, San Francisco, CA 94143 USA. [Brenchley, J. M.] NIAID, Human Immunol Sect, Vaccine Res Ctr, NIH, Bethesda, MD 20892 USA. [Reeves, J. D.] Monogram Biosci, San Francisco, CA USA. [Gordon, S. N.; Silvestri, G.] Univ Penn, Philadelphia, PA 19104 USA. [Else, J. G.] Emory Univ, Yerkes Natl Primate Res Ctr, Atlanta, GA 30322 USA. [O'Neill, E.] Ctr Dis Control Influenza Div, Atlanta, GA USA. RI Reeves, Jacqueline/I-5379-2012 NR 0 TC 0 Z9 0 U1 0 U2 0 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1742-4690 J9 RETROVIROLOGY JI Retrovirology PY 2009 VL 6 AR P26 PG 1 WC Virology SC Virology GA 509KL UT WOS:000271015300079 ER PT J AU Morner, A Scholler, J Bunnik, E Jansson, M Wehlin, L Bergqvist, L Pihlainen, EH Shaw, O Seidl, T Wang, Y Bergmeier, LA Singh, M Vaughan, R Yang, G Shao, Y Wyatt, RT Schuitemaker, H Biberfeld, G Thorstensson, R Lehner, T AF Morner, A. Scholler, J. Bunnik, E. Jansson, M. Wehlin, L. Bergqvist, L. Pihlainen, E. Hansson Shaw, O. Seidl, T. Wang, Y. Bergmeier, L. A. Singh, M. Vaughan, R. Yang, G. Shao, Y. Wyatt, R. T. Schuitemaker, H. Biberfeld, G. Thorstensson, R. Lehner, T. TI Immunisation with recombinant HLA class I and II, HIV-1gp140 and SIVp27 antigens elicits protection against SHIV-SF162P4 infection in rhesus macaques SO RETROVIROLOGY LA English DT Meeting Abstract C1 [Morner, A.; Jansson, M.; Wehlin, L.; Bergqvist, L.; Pihlainen, E. Hansson; Biberfeld, G.; Thorstensson, R.] Swedish Inst Infect Dis Control, Dept Immunol & Vaccinol, Solna, Sweden. [Scholler, J.] Immudex, Copenhagen, Denmark. [Bunnik, E.; Schuitemaker, H.] Univ Amsterdam, Acad Med Ctr, NL-1105 AZ Amsterdam, Netherlands. [Shaw, O.; Vaughan, R.] Guys Kings & St Thomas Hosp, London, England. [Seidl, T.; Wang, Y.; Lehner, T.] Kings Coll London, Guys Hosp, London WC2R 2LS, England. [Bergmeier, L. A.] Barts & London Queen Marys Sch Med & Dent, London, England. [Singh, M.] LIONEX Diagnost & Therapeut, Braunschweig, Germany. [Yang, G.; Shao, Y.] Chinese Ctr Dis Control, Beijing, Peoples R China. [Wyatt, R. T.] NIAID, Vaccine Res Ctr, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1742-4690 J9 RETROVIROLOGY JI Retrovirology PY 2009 VL 6 AR P328 PG 2 WC Virology SC Virology GA 509KL UT WOS:000271015300379 ER PT J AU Pahwa, S Pallikkuth, S Rogers, KA Doster, M Villinger, F Franchini, G AF Pahwa, S. Pallikkuth, S. Rogers, K. A. Doster, M. Villinger, F. Franchini, G. TI Interleukin (IL)-21 induces cytolytic molecule perforin in CD4 and CD8 T cells without CD4 activation in chronically SIV infected rhesus macaques SO RETROVIROLOGY LA English DT Meeting Abstract C1 [Pahwa, S.; Pallikkuth, S.] Univ Miami, Miller Sch Med, Miami, FL 33136 USA. [Rogers, K. A.; Villinger, F.] Emory Univ, Atlanta, GA 30322 USA. [Doster, M.; Franchini, G.] NCI, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1742-4690 J9 RETROVIROLOGY JI Retrovirology PY 2009 VL 6 AR P276 PG 1 WC Virology SC Virology GA 509KL UT WOS:000271015300327 ER PT J AU Pancera, M Majeed, S Ban, Y Chen, L Huang, C Kong, L Kwon, Y Stuckey, J Zhou, T Robinson, J Schief, W Sodroski, J Wyatt, R Kwong, P AF Pancera, M. Majeed, S. Ban, Y. Chen, L. Huang, C. Kong, L. Kwon, Y. Stuckey, J. Zhou, T. Robinson, J. Schief, W. Sodroski, J. Wyatt, R. Kwong, P. TI Structure of HIV-1 gp41 interactive region: layered architecture and basis of conformational mobility SO RETROVIROLOGY LA English DT Meeting Abstract C1 [Pancera, M.; Majeed, S.; Chen, L.; Huang, C.; Kong, L.; Kwon, Y.; Stuckey, J.; Zhou, T.; Wyatt, R.; Kwong, P.] NIAID, NIH, VRC, Bethesda, MD 20892 USA. [Ban, Y.; Schief, W.] Univ Washington, Seattle, WA 98195 USA. [Robinson, J.] Tulane Univ, Med Ctr, Dept Pediat, New Orleans, LA 70118 USA. [Sodroski, J.] Dana Farber Canc Inst, Dept Canc Immunol & AIDS, Boston, MA 02115 USA. RI Zhou, Tongqing/A-6880-2010 OI Zhou, Tongqing/0000-0002-3935-4637 NR 0 TC 0 Z9 0 U1 0 U2 0 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1742-4690 J9 RETROVIROLOGY JI Retrovirology PY 2009 VL 6 AR P126 PG 2 WC Virology SC Virology GA 509KL UT WOS:000271015300178 ER PT J AU Patterson, J Li, Q Kuate, S McKinnon, K DiPasquale, J Haase, AT Robert-Guroff, M AF Patterson, J. Li, Q. Kuate, S. McKinnon, K. DiPasquale, J. Haase, A. T. Robert-Guroff, M. TI Replicating adenovirus type 5 host range recombinant vaccine biodistribution in rhesus macaques following multiple mucosal routes of immunization SO RETROVIROLOGY LA English DT Meeting Abstract C1 [Patterson, J.; Kuate, S.; McKinnon, K.; DiPasquale, J.; Robert-Guroff, M.] NCI, Bethesda, MD 20892 USA. [Li, Q.; Haase, A. T.] Univ Minnesota, Sch Med, Dept Microbiol, Minneapolis, MN 55455 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1742-4690 J9 RETROVIROLOGY JI Retrovirology PY 2009 VL 6 AR P355 PG 1 WC Virology SC Virology GA 509KL UT WOS:000271015300406 ER PT J AU Pavlakis, GN Rosati, M Patel, V Valentin, A Bergamaschi, C Kulkarni, V Jalah, R von Gegerfelt, A Ohlen, C Khan, A Draghia-Akli, R Van Rompay, K Felber, BK AF Pavlakis, G. N. Rosati, M. Patel, V. Valentin, A. Bergamaschi, C. Kulkarni, V. Jalah, R. von Gegerfelt, A. Ohlen, C. Khan, A. Draghia-Akli, R. Van Rompay, K. Felber, B. K. TI Intramuscular DNA delivery by electroporation leads to greatly enhanced systemic and mucosal immune responses and control of SIVmac251 challenge SO RETROVIROLOGY LA English DT Meeting Abstract C1 [Pavlakis, G. N.; Rosati, M.; Patel, V.; Valentin, A.; Bergamaschi, C.; von Gegerfelt, A.] NCI, Ctr Canc Res, HRS, VB, Frederick, MD 21701 USA. [Ohlen, C.] NCI, SAIC Frederick Inc, ACVP, Frederick, MD 21701 USA. [Khan, A.; Draghia-Akli, R.] VGX Pharmaceut Inc, The Woodlands, TX USA. [Van Rompay, K.] Calif Natl Reg Primate Res Ctr, Davis, CA USA. [Kulkarni, V.; Jalah, R.; Felber, B. K.] NCI, HRPS, VB, Frederick, MD 21701 USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1742-4690 J9 RETROVIROLOGY JI Retrovirology PY 2009 VL 6 AR P196 PG 1 WC Virology SC Virology GA 509KL UT WOS:000271015300247 ER PT J AU Pegu, A Migone, T Freimuth, W Donaldson, M Foulds, K Roederer, M Nabel, GJ AF Pegu, A. Migone, T. Freimuth, W. Donaldson, M. Foulds, K. Roederer, M. Nabel, G. J. TI A human blocking antibody to CCR5 partially protects against lentiviral infection in non-human primates SO RETROVIROLOGY LA English DT Meeting Abstract C1 [Pegu, A.; Donaldson, M.; Foulds, K.; Roederer, M.; Nabel, G. J.] NIH, Bethesda, MD 20892 USA. [Migone, T.; Freimuth, W.] Human Genome Sci, Rockville, MD USA. OI Pegu, Amarendra/0000-0003-3564-6453 NR 0 TC 0 Z9 0 U1 0 U2 0 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1742-4690 J9 RETROVIROLOGY JI Retrovirology PY 2009 VL 6 AR P402 PG 1 WC Virology SC Virology GA 509KL UT WOS:000271015300453 ER PT J AU Pegu, A Boyington, JC Kong, W Shi, W Kwong, PD Nabel, GJ AF Pegu, A. Boyington, J. C. Kong, W. Shi, W. Kwong, P. D. Nabel, G. J. TI Crystal structure and function of a monoclonal antibody against primate CD4 that blocks HIV/SIV infection SO RETROVIROLOGY LA English DT Meeting Abstract C1 [Pegu, A.; Boyington, J. C.; Kong, W.; Shi, W.; Kwong, P. D.; Nabel, G. J.] NIAID, Vaccine Res Ctr, NIH, Bethesda, MD 20892 USA. OI Pegu, Amarendra/0000-0003-3564-6453 NR 0 TC 0 Z9 0 U1 0 U2 0 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1742-4690 J9 RETROVIROLOGY JI Retrovirology PY 2009 VL 6 AR P183 PG 1 WC Virology SC Virology GA 509KL UT WOS:000271015300234 ER PT J AU Robinson, HL Amara, RR Lai, L Xu, Y De Rosa, S Defawe, O Sato, A Tomaras, GD Qin, L Moss, B Wyatt, LS Hay, C Goepfert, P AF Robinson, H. L. Amara, R. R. Lai, L. Xu, Y. De Rosa, S. Defawe, O. Sato, A. Tomaras, G. D. Qin, L. Moss, B. Wyatt, L. S. Hay, C. Goepfert, P. TI Comparison of the immunogenicity in humans and rhesus macaques of vaccines consisting of DNA priming and MVA boosting and MVA priming and boosting SO RETROVIROLOGY LA English DT Meeting Abstract C1 [Robinson, H. L.; Xu, Y.] GeoVax Inc, Atlanta, GA USA. [Amara, R. R.; Lai, L.] Yerkes Natl Primate Res Ctr, Atlanta, GA USA. [Amara, R. R.; Lai, L.] Emory Vaccine Ctr, Atlanta, GA USA. [De Rosa, S.; Defawe, O.; Sato, A.] Fred Hutchinson Canc Res Ctr, HVTN Lab Program, Seattle, WA 98104 USA. [Tomaras, G. D.] Duke Univ, Med Ctr, Durham, NC USA. [Qin, L.] Fred Hutchinson Canc Res Ctr, HVTN SCHARP, Seattle, WA 98104 USA. [Wyatt, L. S.] NIAID, NIH, Bethesda, MD 20892 USA. [Hay, C.] Univ Rochester, Rochester, NY USA. [Goepfert, P.] Univ Alabama, Alabama Vaccine Res Clin, Birmingham, AL USA. RI Tomaras, Georgia/J-5041-2016 NR 0 TC 0 Z9 0 U1 0 U2 0 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1742-4690 J9 RETROVIROLOGY JI Retrovirology PY 2009 VL 6 AR P422 PG 2 WC Virology SC Virology GA 509KL UT WOS:000271015300473 ER PT J AU Rood, JE Migueles, SA Berkley, AM Compton, AA Joshi, RP Duerr, A McElrath, J Connors, M AF Rood, J. E. Migueles, S. A. Berkley, A. M. Compton, A. A. Joshi, R. P. Duerr, A. McElrath, J. Connors, M. TI HIV-specific CD8+T-cells of vaccinees exhibit proliferative and cytotoxic capacities comparable to those of progressors SO RETROVIROLOGY LA English DT Meeting Abstract C1 [Rood, J. E.; Migueles, S. A.; Berkley, A. M.; Compton, A. A.; Joshi, R. P.; Connors, M.] NIH, Bethesda, MD 20892 USA. [Duerr, A.; McElrath, J.] Fred Hutchinson Canc Res Ctr, Vaccine & Infect Dis Unit, Seattle, WA 98104 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1742-4690 J9 RETROVIROLOGY JI Retrovirology PY 2009 VL 6 AR O49 PG 1 WC Virology SC Virology GA 509KL UT WOS:000271015300050 ER PT J AU Sanville, B Buckler-White, A Yan, YH Dolan, M Wollenberg, K Kozak, CA AF Sanville, Bradley Buckler-White, Alicia Yan, Yuhe Dolan, Michael Wollenberg, Kurt Kozak, Christine A. TI Adaptive evolution of the virus resistance gene Apobec in the genus Mus SO RETROVIROLOGY LA English DT Meeting Abstract C1 [Sanville, Bradley; Buckler-White, Alicia; Yan, Yuhe; Kozak, Christine A.] NIAID, Mol Microbiol Lab, Bethesda, MD 20892 USA. [Dolan, Michael; Wollenberg, Kurt] NIAID, Bioinformat & Computat Biosci Branch, Off Cyber Infrastruct & Computat Biol, Bethesda, MD 20892 USA. NR 1 TC 0 Z9 0 U1 0 U2 0 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1742-4690 J9 RETROVIROLOGY JI Retrovirology PY 2009 VL 6 AR O7 PG 1 WC Virology SC Virology GA 498MX UT WOS:000270146200032 ER PT J AU Sarzotti-Kelsoe, M Cox, J Cleland, N Denny, T Hural, J Needham, L Ozaki, D Rodriguez-Chavez, IR Stevens, G Stiles, T Tarragona-Fiol, T Simkins, A AF Sarzotti-Kelsoe, M. Cox, J. Cleland, N. Denny, T. Hural, J. Needham, L. Ozaki, D. Rodriguez-Chavez, I. R. Stevens, G. Stiles, T. Tarragona-Fiol, T. Simkins, A. TI Evaluation and recommendations on good clinical laboratory practice (GCLP) guidelines for phase I-III HIV vaccine clinical trials SO RETROVIROLOGY LA English DT Meeting Abstract C1 [Sarzotti-Kelsoe, M.] Duke Univ, Med Ctr, Durham, NC USA. [Sarzotti-Kelsoe, M.] Int AIDS Vaccine Initiat, Rockville, MD USA. [Cleland, N.] NIAID, DAIDS, NIH, Bethesda, MD 20892 USA. [Denny, T.; Needham, L.] CHAVI, Duke Human Vaccine Inst, Durham, NC USA. [Hural, J.] HIV Vaccine Trials Network, Seattle, WA USA. [Ozaki, D.] CAVD CA VIMC Cent QAU, Durham, NC USA. [Rodriguez-Chavez, I. R.] NIDCR, AIDS & Immunosuppress Program, IBIDB, DER,NIH, Bethesda, MD USA. [Stiles, T.] Qual Ltd, Kettering, England. [Cox, J.; Stevens, G.; Tarragona-Fiol, T.] Univ London Imperial Coll Sci Technol & Med, Int AIDS Vaccine Initiat Core Lab, London, England. [Simkins, A.] AlphaVax Human Vaccines Inc, Res Triangle Pk, NC USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1742-4690 J9 RETROVIROLOGY JI Retrovirology PY 2009 VL 6 AR P206 PG 1 WC Virology SC Virology GA 509KL UT WOS:000271015300257 ER PT J AU Sirivichayakul, S Felber, B Kulkarni, V Pavlakis, G Buranapraditkun, S Thantiworasit, P Pitakpolrat, P Allen, T Leitner, T Korber, B Ruxrungtham, K AF Sirivichayakul, S. Felber, B. Kulkarni, V. Pavlakis, G. Buranapraditkun, S. Thantiworasit, P. Pitakpolrat, P. Allen, T. Leitner, T. Korber, B. Ruxrungtham, K. TI Pre-clinical immunogenicity of mosaic Asian AE/B HIV-1 DNA vaccine in mice SO RETROVIROLOGY LA English DT Meeting Abstract C1 [Sirivichayakul, S.; Buranapraditkun, S.; Thantiworasit, P.; Pitakpolrat, P.; Ruxrungtham, K.] Chulalongkorn Univ, Fac Med, Dept Med, Bangkok 10330, Thailand. [Felber, B.; Kulkarni, V.; Pavlakis, G.] NCI, Frederick, MD 21701 USA. [Allen, T.] Harvard Univ, Sch Med, Boston, MA USA. [Leitner, T.; Korber, B.] Los Alamos Natl Lab, Los Alamos, NM USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1742-4690 J9 RETROVIROLOGY JI Retrovirology PY 2009 VL 6 AR P321 PG 1 WC Virology SC Virology GA 509KL UT WOS:000271015300372 ER PT J AU Sitar, S Hartman, BI Graham, BS Ledgerwood, JE AF Sitar, S. Hartman, B. I. Graham, B. S. Ledgerwood, J. E. TI Social media as a tool for engaging and educating audiences around HIV vaccine research and clinical trial participation SO RETROVIROLOGY LA English DT Meeting Abstract C1 [Sitar, S.; Hartman, B. I.; Graham, B. S.; Ledgerwood, J. E.] NIAID, Vaccine Res Ctr, NIH, Bethesda, MD 20892 USA. NR 0 TC 1 Z9 1 U1 1 U2 5 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1742-4690 J9 RETROVIROLOGY JI Retrovirology PY 2009 VL 6 AR P218 PG 1 WC Virology SC Virology GA 509KL UT WOS:000271015300269 ER PT J AU Strbo, N Vaccari, M Pahwa, S Kolber, MA Fisher, E Gonzalez, L Felber, BK Pavlakis, GN Franchini, G Podack, ER AF Strbo, N. Vaccari, M. Pahwa, S. Kolber, M. A. Fisher, E. Gonzalez, L. Felber, B. K. Pavlakis, G. N. Franchini, G. Podack, E. R. TI Gp96-Ig-SIV vaccines induce predominant immune responses at mucosal sites SO RETROVIROLOGY LA English DT Meeting Abstract C1 [Strbo, N.; Pahwa, S.; Kolber, M. A.; Fisher, E.; Gonzalez, L.; Podack, E. R.] Univ Miami, Miller Sch Med, Miami, FL 33136 USA. [Vaccari, M.; Felber, B. K.; Pavlakis, G. N.; Franchini, G.] NCI, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1742-4690 J9 RETROVIROLOGY JI Retrovirology PY 2009 VL 6 AR O34 PG 2 WC Virology SC Virology GA 509KL UT WOS:000271015300035 ER PT J AU Strebel, K AF Strebel, Klaus TI Antagonizing the effects of Bst-2/tetherin: multiple ways to accomplish a common goal SO RETROVIROLOGY LA English DT Meeting Abstract C1 [Strebel, Klaus] NIAID, Viral Biochem Sect, LMM, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1742-4690 J9 RETROVIROLOGY JI Retrovirology PY 2009 VL 6 AR I10 PG 1 WC Virology SC Virology GA 498MX UT WOS:000270146200011 ER PT J AU Sui, Y Zhu, Q Gagnon, S Dzutsev, A Terabe, M Vaccari, M Venzon, D Klinman, D Strober, W Kelsall, B Franchini, G Belyakov, IM Berzofsky, JA AF Sui, Y. Zhu, Q. Gagnon, S. Dzutsev, A. Terabe, M. Vaccari, M. Venzon, D. Klinman, D. Strober, W. Kelsall, B. Franchini, G. Belyakov, I. M. Berzofsky, J. A. TI Role of vaccine-induced innate and adaptive immunity in controlling mucosal transmission of SIV in macaques SO RETROVIROLOGY LA English DT Meeting Abstract C1 [Venzon, D.] NCI, Biostat Branch, NIH, Bethesda, MD 20892 USA. [Klinman, D.] NCI, Expt Immunol Lab, NIH, Bethesda, MD 20892 USA. [Strober, W.] NIAID, Host Def Lab, NIH, Bethesda, MD 20892 USA. [Kelsall, B.] NIAID, Lab Molec Immunol, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1742-4690 J9 RETROVIROLOGY JI Retrovirology PY 2009 VL 6 AR P414 PG 2 WC Virology SC Virology GA 509KL UT WOS:000271015300465 ER PT J AU Sundling, C Soldemo, M Chakrabarti, B Forsell, MN Lore, K Wyatt, RT Douagi, I AF Sundling, C. Soldemo, M. Chakrabarti, B. Forsell, M. N. Lore, K. Wyatt, R. T. Douagi, I. TI Evaluation of peripheral and bone marrow B cell responses in rhesus macaques after immunization with soluble HIV-1 gp140 trimers SO RETROVIROLOGY LA English DT Meeting Abstract C1 [Sundling, C.; Soldemo, M.; Douagi, I.] Karolinska Inst, Stockholm, Sweden. [Chakrabarti, B.; Forsell, M. N.; Wyatt, R. T.] NIH, Vaccine Res Ctr, Bethesda, MD 20892 USA. [Lore, K.] Karolinska Inst, Ctr Infect Med, Stockholm, Sweden. NR 0 TC 0 Z9 0 U1 0 U2 1 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1742-4690 J9 RETROVIROLOGY JI Retrovirology PY 2009 VL 6 AR P83 PG 2 WC Virology SC Virology GA 509KL UT WOS:000271015300135 ER PT J AU Valentin, A von Gegerfelt, A Alicea, C Patel, V Marthas, ML Van Rompay, K Pavlakis, GN Felber, BK AF Valentin, A. von Gegerfelt, A. Alicea, C. Patel, V. Marthas, M. L. Van Rompay, K. Pavlakis, G. N. Felber, B. K. TI Altered mucosal distribution of SIV-specific T cells in Rhesus macaques infected with the live-attenuated Rev-independent SIV SO RETROVIROLOGY LA English DT Meeting Abstract C1 [Valentin, A.; von Gegerfelt, A.; Patel, V.; Pavlakis, G. N.] NCI, Ctr Canc Res, HRS, VB, Frederick, MD 21701 USA. [Alicea, C.; Felber, B. K.] NCI, HRPS, VB, Frederick, MD 21701 USA. [Marthas, M. L.; Van Rompay, K.] Calif Natl Reg Primate Res Ctr, Davis, CA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1742-4690 J9 RETROVIROLOGY JI Retrovirology PY 2009 VL 6 AR P164 PG 2 WC Virology SC Virology GA 509KL UT WOS:000271015300215 ER PT J AU Verkoczy, L Diaz, M Holl, TM Ouyang, Y Bouton-Verville, H Alam, SM Liao, H Kelsoe, G Haynes, BF AF Verkoczy, L. Diaz, M. Holl, T. M. Ouyang, Y. Bouton-Verville, H. Alam, S. M. Liao, H. Kelsoe, G. Haynes, B. F. TI Immunological tolerance prevents the expression of a broadly reactive neutralizing HIV-1 antibody SO RETROVIROLOGY LA English DT Meeting Abstract C1 [Verkoczy, L.; Bouton-Verville, H.; Alam, S. M.; Liao, H.; Haynes, B. F.] Duke Univ, Med Ctr, Duke Human Vaccine Inst, Durham, NC USA. [Diaz, M.] NIEHS, Res Triangle Pk, NC 27709 USA. [Holl, T. M.; Kelsoe, G.] Duke Univ, Med Ctr, Dept Immunol, Durham, NC USA. [Ouyang, Y.] Xenogen Biosci, Cranbury, NJ USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1742-4690 J9 RETROVIROLOGY JI Retrovirology PY 2009 VL 6 AR P54 PG 1 WC Virology SC Virology GA 509KL UT WOS:000271015300107 ER PT J AU Wang, Y Whittall, T Scholler, J Wyatt, R Singh, M Bergmeier, LA Bunnik, E Schuitemaker, H Shaw, O Vaughan, R Pido-Lopez, J Seidl, T Babaahmady, K Yang, G Thorstensson, R Biberfeld, G Lehner, T AF Wang, Y. Whittall, T. Scholler, J. Wyatt, R. Singh, M. Bergmeier, L. A. Bunnik, E. Schuitemaker, H. Shaw, O. Vaughan, R. Pido-Lopez, J. Seidl, T. Babaahmady, K. Yang, G. Thorstensson, R. Biberfeld, G. Lehner, T. TI Allogeneic stimulation of the anti-viral APOBEC3G in human CD4+T cells and prevention of SHIV infectivity in macaques immunized with HLA antigens SO RETROVIROLOGY LA English DT Meeting Abstract C1 [Wang, Y.; Whittall, T.; Bergmeier, L. A.; Shaw, O.; Vaughan, R.; Pido-Lopez, J.; Seidl, T.; Babaahmady, K.; Lehner, T.] Kings Coll London, Mucosal Immunol Unit, London WC2R 2LS, England. [Scholler, J.] Immunodex, Copenhagen, Denmark. [Wyatt, R.] NIH, Bethesda, MD 20892 USA. [Singh, M.] Lionex Diagnost & Therapeut, Braunschweig, Germany. [Bunnik, E.; Schuitemaker, H.] Univ Amsterdam, Acad Med Ctr, NL-1105 AZ Amsterdam, Netherlands. [Yang, G.] Chinese Ctr Dis Control & Prevent, Beijing, Peoples R China. [Thorstensson, R.; Biberfeld, G.] Swedish Inst Infect Dis Control, Stockholm, Sweden. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1742-4690 J9 RETROVIROLOGY JI Retrovirology PY 2009 VL 6 AR P340 PG 1 WC Virology SC Virology GA 509KL UT WOS:000271015300391 ER PT J AU Wu, X Zhou, T O'Dell, S Wyatt, RT Kwong, PD Mascola, JR AF Wu, X. Zhou, T. O'Dell, S. Wyatt, R. T. Kwong, P. D. Mascola, J. R. TI Mechanism of HIV-1 resistance to a monoclonal antibody that effectively targets the site of CD4 attachment SO RETROVIROLOGY LA English DT Meeting Abstract C1 [Wu, X.; Zhou, T.; O'Dell, S.; Wyatt, R. T.; Kwong, P. D.; Mascola, J. R.] NIAID, Vaccine Res Ctr, NIH, Bethesda, MD 20892 USA. RI Zhou, Tongqing/A-6880-2010 OI Zhou, Tongqing/0000-0002-3935-4637 NR 0 TC 0 Z9 0 U1 0 U2 0 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1742-4690 J9 RETROVIROLOGY JI Retrovirology PY 2009 VL 6 AR P118 PG 1 WC Virology SC Virology GA 509KL UT WOS:000271015300170 ER PT J AU Wyatt, L Earl, P Moss, B AF Wyatt, L. Earl, P. Moss, B. TI Assessing and restructuring foreign gene insertion sites for enhanced stability of modified Vaccinia virus ankara recombinants expressing HIV genes SO RETROVIROLOGY LA English DT Meeting Abstract C1 [Wyatt, L.; Earl, P.; Moss, B.] NIAID, LVD, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1742-4690 J9 RETROVIROLOGY JI Retrovirology PY 2009 VL 6 AR P416 PG 1 WC Virology SC Virology GA 509KL UT WOS:000271015300467 ER PT J AU Xiao, X Feng, Y Chen, W Longo, N Dimitrov, DS AF Xiao, X. Feng, Y. Chen, W. Longo, N. Dimitrov, D. S. TI Guiding the immune system through complex maturation pathways: a novel multi-immunogen approach for elicitation of broadly neutralizing antibodies SO RETROVIROLOGY LA English DT Meeting Abstract C1 [Xiao, X.; Feng, Y.; Chen, W.; Dimitrov, D. S.] NCI, CCRNP, NIH, Frederick, MD 21701 USA. [Longo, N.] NIAMSD, Bethesda, MD 20892 USA. NR 0 TC 1 Z9 1 U1 0 U2 1 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1742-4690 J9 RETROVIROLOGY JI Retrovirology PY 2009 VL 6 AR P35 PG 2 WC Virology SC Virology GA 509KL UT WOS:000271015300088 ER PT J AU Yu, B Houzet, L Didierlaurent, L Chamontin, C Morichaud, Z Darlix, JL Mougel, M AF Yu, Bing Houzet, Laurent Didierlaurent, Ludovic Chamontin, Celia Morichaud, Zakia Darlix, Jean Luc Mougel, Marylene TI A new role of the HIV-1 nucleocapsid in the spatiotemporal control of the reverse transcription throughout the virus replication cycle SO RETROVIROLOGY LA English DT Meeting Abstract ID MUTATIONS; TYPE-1 C1 [Yu, Bing; Houzet, Laurent; Didierlaurent, Ludovic; Chamontin, Celia; Morichaud, Zakia; Mougel, Marylene] Inst Biol, CPBS Equipe Assemblage & Replicat Retrovirus, UMI UMII, CNRS UMR 5236, Montpellier, France. [Yu, Bing] Huazhong Univ Sci & Technol, Dept Pathogen Biol, Tongji Med Coll, Wuhan 430074, Peoples R China. [Houzet, Laurent] NIAID, Mol Virol Sect, Mol Microbiol Lab, NIH, Bethesda, MD 20892 USA. [Darlix, Jean Luc] ENS, IFR 128, INSERM, Unite Virol Humaine,LaboRetro,U758, Lyon, France. RI Mougel, Marylene/K-7958-2013 OI Mougel, Marylene/0000-0002-0345-1427 NR 5 TC 0 Z9 0 U1 0 U2 1 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1742-4690 J9 RETROVIROLOGY JI Retrovirology PY 2009 VL 6 AR P14 PG 2 WC Virology SC Virology GA 498MX UT WOS:000270146200066 ER PT J AU Zhou, T Yang, Z Xu, L Hessell, AJ Burton, DR Nabel, GJ Kwong, PD AF Zhou, T. Yang, Z. Xu, L. Hessell, A. J. Burton, D. R. Nabel, G. J. Kwong, P. D. TI Crystal structure of gp120 in complex with the CD4-binding-site antibody b13 suggests precise targeting is needed for neutralization SO RETROVIROLOGY LA English DT Meeting Abstract C1 [Zhou, T.; Yang, Z.; Xu, L.; Nabel, G. J.; Kwong, P. D.] NIAID, Vaccine Res Ctr, NIH, Bethesda, MD 20892 USA. [Hessell, A. J.; Burton, D. R.] Scripps Res Inst, La Jolla, CA 92037 USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1742-4690 J9 RETROVIROLOGY JI Retrovirology PY 2009 VL 6 AR P66 PG 1 WC Virology SC Virology GA 509KL UT WOS:000271015300118 ER PT J AU Cammarata, M Eybert, L Ewald, F Reichenbach, W Wulff, M Anfinrud, P Schotte, F Plech, A Kong, QY Lorenc, M Lindenau, B Rabiger, J Polachowski, S AF Cammarata, Marco Eybert, Laurent Ewald, Friederike Reichenbach, Wolfgang Wulff, Michael Anfinrud, Philip Schotte, Friedrich Plech, Anton Kong, Qingyu Lorenc, Maciej Lindenau, Bernd Raebiger, Juergen Polachowski, Stephan TI Chopper system for time resolved experiments with synchrotron radiation SO REVIEW OF SCIENTIFIC INSTRUMENTS LA English DT Article DE beam choppers; high-speed techniques; synchrotron radiation; X-ray apparatus ID X-RAY-DIFFRACTION; STRUCTURAL DYNAMICS; MECHANICAL SHUTTER; BEAM CHOPPER; CRYSTALLOGRAPHY; REALIZATION; PROTEIN; COMPLEX; ESRF AB A chopper system for time resolved pump-probe experiments with x-ray beams from a synchrotron is described. The system has three parts: a water-cooled heatload chopper, a high-speed chopper, and a millisecond shutter. The chopper system, which is installed in beamline ID09B at the European Synchrotron Radiation Facility, provides short x-ray pulses for pump-probe experiments with ultrafast lasers. The chopper system can produce x-ray pulses as short as 200 ns in a continuous beam and repeat at frequencies from 0 to 3 kHz. For bunch filling patterns of the synchrotron with pulse separations greater than 100 ns, the high-speed chopper can isolate single 100 ps x-ray pulses that are used for the highest time resolution. A new rotor in the high-speed chopper is presented with a single pulse (100 ps) and long pulse (10 mu s) option. In white beam experiments, the heatload of the (noncooled) high-speed chopper is lowered by a heatload chopper, which absorbs 95% of the incoming power without affecting the pulses selected by the high speed chopper. C1 [Cammarata, Marco; Eybert, Laurent; Ewald, Friederike; Reichenbach, Wolfgang; Wulff, Michael] European Synchrotron Radiat Facil, F-38043 Grenoble, France. [Anfinrud, Philip; Schotte, Friedrich] NIH, Chem Phys Lab, Bethesda, MD 20892 USA. [Plech, Anton] Forschungszentrum Karlsruhe, Inst Synchrotron Radiat ISS, D-76021 Karlsruhe, Germany. [Kong, Qingyu] Synchrotron SOLEIL, F-91192 Gif Sur Yvette, France. [Lorenc, Maciej] Univ Rennes 1, CNRS, UMR6626, Grp Mat Condensee & Mat, F-35042 Rennes, France. [Lindenau, Bernd; Raebiger, Juergen; Polachowski, Stephan] Forschungszentrum Julich, Cent Technol Div ZAT, D-52425 Julich, Germany. RP Wulff, M (reprint author), European Synchrotron Radiat Facil, BP 220, F-38043 Grenoble, France. EM wulff@esrf.fr RI Cammarata, Marco/C-2322-2008; Plech, Anton/E-4895-2010; Lorenc, Maciej/N-7594-2014; OI Cammarata, Marco/0000-0003-3013-1186; Plech, Anton/0000-0002-6290-9303 NR 22 TC 48 Z9 48 U1 3 U2 22 PU AMER INST PHYSICS PI MELVILLE PA CIRCULATION & FULFILLMENT DIV, 2 HUNTINGTON QUADRANGLE, STE 1 N O 1, MELVILLE, NY 11747-4501 USA SN 0034-6748 J9 REV SCI INSTRUM JI Rev. Sci. Instrum. PD JAN PY 2009 VL 80 IS 1 AR 015101 DI 10.1063/1.3036983 PG 10 WC Instruments & Instrumentation; Physics, Applied SC Instruments & Instrumentation; Physics GA 401TT UT WOS:000262966000035 PM 19191457 ER PT S AU Chao, CC Garland, DL Dasch, GA Ching, WM AF Chao, Chien-Chung Garland, Donita L. Dasch, Gregory A. Ching, Wei-Mei BE Hechemy, KE Brouqui, P Samuel, JE Raoult, DA TI Comparative Proteomic Analysis of Antibiotic-Sensitive and Insensitive Isolates of Orientia tsutsugamushi SO RICKETTSIOLOGY AND RICKETTSIAL DISEASES SE ANNALS OF THE NEW YORK ACADEMY OF SCIENCES LA English DT Article; Proceedings Paper CT 5th International Conference on Rickettsiae and Rickettsial Diseases CY MAY 18-20, 2008 CL Marseilles, FRANCE DE Orientia tsutsugamushi; Proteomic; antibiotic sensitive ID SCRUB TYPHUS; RESISTANCE AB Scrub typhus, caused by infection with Orientia tsutsugamushi, is probably the most common severe rickettsial disease. Early diagnosis followed by treatment with antibiotics such as doxycycline or chloramphenicol usually quickly decreases fever in patients, and they often recover well from other symptoms of the disease. However, poorly responsive cases have been reported from northern Thailand and southern India. In order to identify protein factors that may be partially responsible for differential drug sensitivity of isolates of Orientia, we compared the protein profiles of doxycycline sensitive (Karp) versus (vs.) insensitive (AFSC4 and AFSC7) isolates. Tryptic peptides from both total water-soluble proteins and from protein spots separated by 2D-PAGE were analyzed using LC-MS/MS. The identity of each protein was established using the published genomic sequence of Boryong strain O. tsutsugamushi. The profiles of protein released into water from these isolates were quite different. There were 10 proteins detected only in AFSC4, 3 only in Karp, and I only in AFSC7. Additionally, there were 2 proteins not detected only in AFSC4,4 not found only in Karp, and 3 not found only in AFSC-7. A comparison of 2D-PAGE protein profiles of drug sensitive strain versus (vs.) insensitive isolates has led to the identification of 14 differentially expressed or localized proteins, including elongation factor Ts and Tu, DNA-directed RNA polymerase alpha-subunit, ATP synthase beta-subunit, and several hypothetical proteins. These data confirm the tremendous proteomic diversity of isolates of Orientia and suggest that drug insensitivity in this species may arise from multiple mechanisms. C1 [Chao, Chien-Chung; Ching, Wei-Mei] USN, VRDD, IDD, Med Res Ctr, Silver Spring, MD 20910 USA. [Garland, Donita L.] NEI, NIH, Bethesda, MD 20892 USA. [Dasch, Gregory A.] Ctr Dis Control & Prevent, Rickettsial Zoonoses Branch, Atlanta, GA 30333 USA. [Ching, Wei-Mei] Uniformed Serv Univ Hlth Sci, Bethesda, MD 20814 USA. RP Chao, CC (reprint author), USN, VRDD, IDD, Med Res Ctr, 503 Robert Grant Ave,RM3N71, Silver Spring, MD 20910 USA. EM chien-chung.chao@med.navy.mil RI Chao, Chien-Chung/A-8017-2011; OI Dasch, Gregory/0000-0001-6090-1810 FU Work Unit Number (WUN [6000.RAD1.J.A0310] FX The authors wish to thank Ms. Kynita Winn for her help in 2D-PAGE analysis and Dr. Paul Graf for his review of the manuscript. This work was Supported by Work Unit Number (WUN) 6000.RAD1.J.A0310. The opinions and assertions contained herein are the private ones of the authors and are not to be construed as official or as reflecting the views of the Department of the Navy, the naval service at large, the Department of Defense, the Centers for Disease Control and Prevention, the Department of Health and Human Services, or the U. S. Government. Authors C. C. Chao, G. A. Dasch, and W M. Ching are employees of the U. S. Government. This work was prepared as part of official duties. NR 18 TC 4 Z9 4 U1 1 U2 3 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXEN, ENGLAND SN 0077-8923 BN 978-1-57331-750-4 J9 ANN NY ACAD SCI JI Ann.NY Acad.Sci. PY 2009 VL 1166 BP 27 EP 37 DI 10.1111/j.1749-6632.2009.04525.x PG 11 WC Infectious Diseases; Multidisciplinary Sciences; Parasitology SC Infectious Diseases; Science & Technology - Other Topics; Parasitology GA BJV56 UT WOS:000267264400003 PM 19538261 ER PT S AU Graubard, BI Korn, EL AF Graubard, Barry I. Korn, Edward L. BE Pfeffermann, D Rao, CR TI Scatterplots with Survey Data SO SAMPLE SURVEYS: INFERENCE AND ANALYSIS, VOL 29B SE Handbook of Statistics LA English DT Article; Book Chapter C1 [Graubard, Barry I.] NCI, Biostat Branch, Bethesda, MD 20892 USA. [Korn, Edward L.] NCI, Biometr Res Branch, Bethesda, MD 20892 USA. RP Graubard, BI (reprint author), NCI, Biostat Branch, Execut Plaza,South Bldg,6120 Execut Blvd,Room 802, Bethesda, MD 20892 USA. EM graubarb@mail.nih.gov; korne@mail.nih.gov NR 0 TC 0 Z9 0 U1 0 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA SARA BURGERHARTSTRAAT 25, PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0169-7161 BN 978-0-08-096354-9 J9 HANDB STAT PY 2009 VL 29B BP 397 EP 419 DI 10.1016/S0169-7161(09)00237-5 PG 23 WC Statistics & Probability SC Mathematics GA BCR02 UT WOS:000311051300018 ER PT J AU Scherer, ML Aspelund, T Sigurdsson, S Detrano, R Garcia, M Mitchell, GF Launer, LJ Thorgeirsson, G Gudnason, V Harris, TB AF Scherer, Matthew L. Aspelund, Thor Sigurdsson, Sigurdur Detrano, Robert Garcia, Melissa Mitchell, Gary F. Launer, Lenore J. Thorgeirsson, Gudmundur Gudnason, Vilmundur Harris, Tamara B. TI Abnormal T-wave axis is associated with coronary artery calcification in older adults SO SCANDINAVIAN CARDIOVASCULAR JOURNAL LA English DT Article; Proceedings Paper CT 47th Annual Conference on Cardiovascular Disease Epidemiology and Prevention CY FEB 28-MAR 03, 2007 CL Orlando, FL SP Amer Heart Assoc, Council Epidemiol & Prevent, Council Nutr, Phys Activ & Metab, Natl Heart, Lung & Blood Inst DE Epidemiology; electrocardiography; aging; computed tomography; atherosclerosis ID BEAM COMPUTED-TOMOGRAPHY; PREDICTS CARDIAC DEATH; CARDIOVASCULAR-DISEASE; GENERAL-POPULATION; HEART-DISEASE; CHEST-PAIN; RISK; MEN; ATHEROSCLEROSIS; ANGLE AB Objective. To determine whether T-wave axis on the resting electrocardiogram (ECG) is associated with coronary artery calcification (CAC) score, a measurement of coronary atherosclerosis, in older adults. Methods. The sample consisted of 2004 adults aged 66 and over participating in the prospective, population-based Age-Gene/Environment Susceptibility-Reykjavik Study. The cohort was divided into gender-stratified quartiles based upon Agatston CAC score derived from computerized tomography. Frontal T-axis deviation from 45 degrees was assessed using surface ECG. Statistical analysis was performed with Tobit regression models adjusted for demographic and cardiovascular risk factors. Results. In the entire study population, T-axis deviation from 45 degrees was significantly associated with increasing CAC score in men (p0.001) and women (p=0.03). In men without clinically recognized coronary heart disease (CHD), the association with CAC score remained statistically significant (p=0.02). This association was significant among women without CHD once male CAC cut points were used (p=0.05). Conclusion. An abnormal T-wave axis is associated with an increasing CAC score in this population of Icelandic older adults. This association remains in the subgroup of subjects without clinical CHD. C1 [Scherer, Matthew L.; Garcia, Melissa; Launer, Lenore J.; Harris, Tamara B.] NIA, Lab Epidemiol Demog & Biometry, NIH, Bethesda, MD 20892 USA. [Scherer, Matthew L.] NIH, Howard Hughes Med Inst, Res Scholars Program, Bethesda, MD 20817 USA. [Aspelund, Thor; Sigurdsson, Sigurdur; Thorgeirsson, Gudmundur; Gudnason, Vilmundur] Iceland Heart Assoc, Kopavogur, Iceland. [Detrano, Robert] Univ Calif Los Angeles, Los Angeles, CA USA. [Mitchell, Gary F.] Cardiovasc Engn Inc, Waltham, MA USA. RP Harris, TB (reprint author), 7201 Wisconsin Ave,Suite 3C-309, Bethesda, MD 20892 USA. EM harris99@mail.nih.gov RI Aspelund, Thor/F-4826-2011; Aspelund, Thor/C-5983-2008; Gudnason, Vilmundur/K-6885-2015 OI Aspelund, Thor/0000-0002-7998-5433; Gudnason, Vilmundur/0000-0001-5696-0084 FU Intramural NIH HHS [Z01 AG007380-03]; NIA NIH HHS [N01AG12100] NR 27 TC 2 Z9 2 U1 0 U2 1 PU TAYLOR & FRANCIS AS PI OSLO PA KARL JOHANS GATE 5, NO-0154 OSLO, NORWAY SN 1401-7431 J9 SCAND CARDIOVASC J JI Scand. Cardiovasc. J. PY 2009 VL 43 IS 4 BP 240 EP 248 AR PII 904520580 DI 10.1080/14017430802471483 PG 9 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 474JS UT WOS:000268280200005 PM 18937149 ER PT J AU Barch, DM Carter, CS Arnsten, A Buchanan, RW Cohen, JD Geyer, M Green, MF Krystal, JH Nuechterlein, K Robbins, T Silverstein, S Smith, EE Strauss, M Wykes, T Heinssen, R AF Barch, Deanna M. Carter, Cameron S. Arnsten, Amy Buchanan, Robert W. Cohen, Jonathan D. Geyer, Mark Green, Michael F. Krystal, John H. Nuechterlein, Keith Robbins, Trevor Silverstein, Steven Smith, Edward E. Strauss, Milton Wykes, Til Heinssen, Robert TI Selecting Paradigms From Cognitive Neuroscience for Translation into Use in Clinical Trials: Proceedings of the Third CNTRICS Meeting SO SCHIZOPHRENIA BULLETIN LA English DT Article ID IMPROVE COGNITION; SCHIZOPHRENIA; TARGETS; ENHANCEMENT; RECEPTORS; DEFICITS; AGONISTS; TASKS; SIZE AB This overview describes the goals and objectives of the third conference conducted as part of the Cognitive Neuroscience Treatment Research to Improve Cognition in Schizophrenia (CNTRICS) initiative. This third conference was focused on selecting specific paradigms from cognitive neuroscience that measured the constructs identified in the first CNTRICS meeting, with the goal of facilitating the translation of these paradigms into use in clinical trials contexts. To identify such paradigms, we had an open nomination process in which the field was asked to nominate potentially relevant paradigms and to provide information on several domains relevant to selecting the most promising tasks for each construct (eg, construct validity, neural bases, psychometrics, availability of animal models). Our goal was to identify 1-2 promising tasks for each of the 11 constructs identified at the first CNTRICS meeting. In this overview article, we describe the on-line survey used to generate nominations for promising tasks, the criteria that were used to select the tasks, the rationale behind the criteria, and the ways in which breakout groups worked together to identify the most promising tasks from among those nominated. This article serves as an introduction to the set of 6 articles included in this special issue that provide information about the specific tasks discussed and selected for the constructs from each of 6 broad domains (working memory, executive control, attention, long-term memory, perception, and social cognition). C1 [Barch, Deanna M.] Washington Univ, St Louis, MO 63130 USA. [Carter, Cameron S.] Univ Calif Davis, Davis, CA 95616 USA. [Arnsten, Amy; Krystal, John H.] Yale Univ, New Haven, CT USA. [Buchanan, Robert W.] Maryland Psychiat Res Ctr, Baltimore, MD 21228 USA. [Cohen, Jonathan D.] Princeton Univ, Princeton, NJ 08544 USA. [Geyer, Mark] Univ Calif San Diego, San Diego, CA 92103 USA. [Green, Michael F.] Univ Calif Los Angeles, Semel Inst, Los Angeles, CA USA. [Green, Michael F.] VA Greater Los Angeles Healthcare Syst, Los Angeles, CA USA. [Nuechterlein, Keith] Univ Calif Los Angeles, Los Angeles, CA USA. [Robbins, Trevor] Univ Cambridge, Cambridge, England. [Silverstein, Steven] Univ Med & Dent New Jersey, Rutgers, NJ USA. [Smith, Edward E.] Columbia Univ, New York, NY USA. [Strauss, Milton] Univ New Mexico, Albuquerque, NM USA. [Wykes, Til] Kings Coll London, Inst Psychiat, London, England. [Heinssen, Robert] NIMH, Bethesda, MD 20892 USA. RP Barch, DM (reprint author), Washington Univ, St Louis, MO 63130 USA. EM dbarch@artsci.wustl.edu RI Wykes, Til/B-7894-2008; Wykes, Til/B-3812-2011; Barch, Deanna/G-8638-2013 OI Wykes, Til/0000-0002-5881-8003; FU National Institute of Mental Health (NIMH); Robert Wood Johnson Foundation; National Alliance for Research on Schizophrenia and Depression (NARSAD); McDonnell Foundation; National Institute of Drugs and Alcohol; US Veteran's Administration VISN 22 Mental Illness Research, Education, and Clinical Center; Janssen; Pfizer; GSK Inc FX We would also like to thank Jody Conrad, Carol Cox, and Deb Tussing, whose efforts have been invaluable in the CNTRICS process. Financial Disclosures: Carter receives funding from the National Institute of Mental Health (NIMH), the Robert Wood Johnson Foundation, and National Alliance for Research on Schizophrenia and Depression (NARSAD). Dr Carter has served as a consultant for Pfizer, Eli Lilly, and Roche. Barch receives funding from the NIMH, the McDonnell Foundation, and NARSAD. Dr Buchanan is currently a Data Safety and Management Board (DSMB) member for Pfizer and in the past has served as a DSMB member for Wyeth. He has served as a consultant for: Pfizer, Roche, Memory, GlaxoSmithKline, Astra-Zeneca, Solvay, Sanofi-Aventis, and Organon and has received study medications from Janssen and Ortho-McNeil Neurologics. Dr Geyer has received consulting compensation from Abbott, Acadia, Addex, Amgen, AstraZeneca, Bristol-Myers Squibb, Jazz, Organon, Nura, San Diego Instruments, Serono, and Wyeth-Ayerst. Dr Geyer also has research grant support from National Institute of Drugs and Alcohol, NIMH, and the US Veteran's Administration VISN 22 Mental Illness Research, Education, and Clinical Center. Dr Green received funding form the NIMH and serves as a consultant to Amgen, Acadia, Astellas, Bristol-Myers Squibb, Dainippon Sumitomo Pharma, Eli Lilly, Lundbeck, Memory Pharmaceuticals, Otsuka Pharmaceutical, Sanofi-Aventis Pharmaceuticals, and Solvay. Dr Krystal receives research funding from the NIMH and has served as an advisor or consultant for AstraZeneca Pharmaceuticals; LP Bristol-Myers Squibb; Cypress Bioscience, Inc; Eli Lilly and Co; Forest Laboratories; GlaxoSmithKline; HoustonPharma; Lohocla Research Corporation; Merz Pharmaceuticals; Organon Pharmaceuticals; Pfizer Pharmaceuticals; Tetragenex Pharmaceuticals; and Transcept Pharmaceuticals, Inc. Dr Nuechterlein has received research funding from the NIMH and from Janssen, L. P., and has served as a consultant for Janssen, L. P. Dr Robbins is a stockholder in CeNeS and has share options in Cambridge Cognition. He has served as a consultant to Eli Lilly, GSK, Wyeth, and Allon and has received research funding from Pfizer, GSK Inc and received speaking honoraria from Merck, Sharp and Dohme, Lundbeck, Cephalon, and Cortex. Dr Silverstein Medical Research Institute, Janssen, and AstraZeneca. Dr Strauss, Dr Heinssen, Dr Smith, and Dr Wykes reported no biomedical financial interests or conflicts of interest. Dr Cohen receives research funding from the NIMH. NR 17 TC 73 Z9 74 U1 0 U2 5 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0586-7614 J9 SCHIZOPHRENIA BULL JI Schizophr. Bull. PD JAN PY 2009 VL 35 IS 1 BP 109 EP 114 DI 10.1093/schbul/sbn163 PG 6 WC Psychiatry SC Psychiatry GA 383OK UT WOS:000261682700014 PM 19023126 ER PT J AU Stroup, TS Lieberman, JA McEvoy, JR Davis, SM Swartz, MS Keefe, RSE Miller, AL Rosenheck, RA Hsiao, JK AF Stroup, T. Scott Lieberman, Jeffrey A. McEvoy, Joseph R. Davis, Sonia M. Swartz, Marvin S. Keefe, Richard S. E. Miller, Alexander L. Rosenheck, Robert A. Hsiao, John K. CA Catie Investigators TI Results of phase 3 of the CATIE schizophrenia trial SO SCHIZOPHRENIA RESEARCH LA English DT Article DE Schizophrenia; Clinical trial; Antipsychotic; Effectiveness ID INTERVENTION EFFECTIVENESS CATIE; CLINICAL ANTIPSYCHOTIC TRIALS; RANDOMIZED CONTROLLED-TRIAL; RESISTANT SCHIZOPHRENIA; DRUGS; 2ND-GENERATION; RISPERIDONE; OLANZAPINE; QUETIAPINE; CLOZAPINE AB Objective: The Clinical Antipsychotic Trials of Intervention Effectiveness (CATIE) study examined the comparative effectiveness of antipsychotic treatments for individuals with chronic schizophrenia. Patients who had discontinued antipsychotic treatment in phases I and 2 were eligible for phase 3, in which they selected one of nine antipsychotic regimens with the help of their study doctor. We describe the characteristics of the patients who selected each treatment option and their outcomes. Method: Two hundred and seventy patients entered phase 3. The open-label treatment options were monotherapy with oral aripiprazole, dozapine, clanzapine, perphenazine, quetiapine, risperidone, ziprasidone, long-acting injectable fluphenazine decanoate, or a combination of any two of these treatments. Results: Few patients selected fluphenazine decanoate (n=9) or perphenazine (n=4). Similar numbers selected each of the other options (range 33-41). Of the seven common choices, those who selected clozapine and combination antipsychotic treatment were the most symptomatic, and those who selected aripiprazole and ziprasidone had the highest body mass index. Symptoms improved for all groups, although the improvements were modest for the groups starting with relatively mild levels of symptoms. Side effect profiles of the medications varied considerably but medication discontinuations due to intolerability were rare (7% overall). Conclusions: Patients and their doctors made treatment selections based on clinical factors, including severity of symptoms, response to prior treatments, and physical health status. Fluphenazine decanoate was rarely used among those with evidence of treatment non-adherence and clozapine was underutilized for those with poor previous response. Combination antipsychotic treatment warrants further study. (c) 2008 Elsevier BY. All rights reserved. C1 [Stroup, T. Scott; Davis, Sonia M.] Univ N Carolina, Dept Psychiat, Sch Med, Chapel Hill, NC 27599 USA. [Lieberman, Jeffrey A.] Columbia Univ, New York State Psychiat Inst, Coll Phys & Surg, Dept Psychiat, New York, NY USA. [McEvoy, Joseph R.] Duke Univ, Med Ctr, John Umstead Hosp, Dept Biol Psychiat, Durham, NC 27706 USA. [McEvoy, Joseph R.; Swartz, Marvin S.; Keefe, Richard S. E.] Duke Univ, Med Ctr, Dept Psychiat & Behav Sci, Durham, NC 27706 USA. [Davis, Sonia M.] Quintiles Inc, Res Triangle Pk, NC USA. [Miller, Alexander L.] Univ Texas Hlth Sci Ctr San Antonio, Dept Psychiat, San Antonio, TX 78229 USA. [Rosenheck, Robert A.] Yale Univ, Sch Med, Dept Psychiat, New Haven, CT 06520 USA. [Hsiao, John K.] NIMH, Div Serv & Intervent Res, NIH, Bethesda, MD 20892 USA. RP Stroup, TS (reprint author), Univ N Carolina, Dept Psychiat, Sch Med, CB 7160, Chapel Hill, NC 27599 USA. EM sstroup@med.unc.edu RI Stroup, Thomas/F-9188-2014 OI Stroup, Thomas/0000-0002-3123-0672 FU National Institute of Mental Health [NO1 MH90001] FX Acknowledgement This article was based on results from the Clinical Antipsychotic Trials of Intervention Effectiveness project, supported by the National Institute of Mental Health (NO1 MH90001). The aim of this project is to examine the comparative effectiveness of antipsychotic drugs in conditions for which their use is clinically indicated, including schizophrenia and Alzheimer's disease. The project was carried out by principal investigators from the University of North Carolina, Duke University, the University of Southern California, the University of Rochester, and Yale University in association with Quintiles, Inc.; the program staff of the Division of interventions and Services Research of the NIMH; and investigators from 56 sites in the United States (CATIE Study Investigators Group). AstraZeneca Pharmaceuticals LP, Bristol-Myers Squibb Company, Forest Pharmaceuticals. Inc., Janssen Pharmaceutica Products, L.P., Eli Lilly and Company. Otsuka Pharmaceutical Co., Ltd., Pfizer Inc., and Zenith Goldline Pharmaceuticals, Inc., provided medications for the studies. NR 14 TC 65 Z9 67 U1 2 U2 4 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0920-9964 J9 SCHIZOPHR RES JI Schizophr. Res. PD JAN PY 2009 VL 107 IS 1 BP 1 EP 12 DI 10.1016/j.schres.2008.10.011 PG 12 WC Psychiatry SC Psychiatry GA 404KW UT WOS:000263151500001 PM 19027269 ER PT B AU Carbone, KM AF Carbone, Kathryn M. BE Fratamico, PM Smith, JL Brogden, KA TI Infectious Causes of Chronic Disease: from Hypothesis to Proof SO SEQUELAE AND LONG-TERM CONSEQUENCES OF INFECTIOUS DISEASES LA English DT Article; Book Chapter ID PNEUMOCYSTIS-CARINII PNEUMONIA; COST-EFFECTIVENESS ANALYSIS; BLOOD-STREAM INFECTIONS; LYME-DISEASE; ACQUIRED IMMUNODEFICIENCY; PREVENTIVE STRATEGIES; ECONOMIC BURDEN; HOMOSEXUAL MEN; HIV-INFECTION; SYNDROME AIDS C1 NIH, Bethesda, MD 20892 USA. RP Carbone, KM (reprint author), NIH, MSC 4326,8800 Rockville Pike, Bethesda, MD 20892 USA. NR 76 TC 3 Z9 3 U1 0 U2 1 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N STREET NW, WASHINGTON, DC 20036-2904 USA BN 978-1-55581-430-4 PY 2009 BP 1 EP 8 PG 8 WC Infectious Diseases SC Infectious Diseases GA BKK70 UT WOS:000268393800001 ER PT J AU Singh, AP Harada, S Mishina, Y AF Singh, A. P. Harada, S. Mishina, Y. TI Downstream Genes of Sox8 That Would Affect Adult Male Fertility SO SEXUAL DEVELOPMENT LA English DT Article DE Blood-testis barrier; Male fertility; Sertoli cell; SRY-box; Spermatogenesis ID TRANSCRIPTION FACTOR SOX8; SERTOLI-CELL FUNCTION; JUNCTION DYNAMICS; SEX DETERMINATION; TESTIS; MOUSE; DIFFERENTIATION; EXPRESSION; MICE; SPERMATOGENESIS AB Sertoli cells provide nutritional and physical support to germ cells during spermatogenesis. Sox8 encodes a high mobility group transcription factor closely related to Sox9 and Sox10. Sertoli cells produce SOX8 protein, and its elimination results in an age-dependent deregulation of spermatogenesis resulting in male infertility. This suggests that Sox8 is a critical regulator of Sertoli cell function for the maintenance of male fertility beyond the first wave of spermatogenesis. To better understand the roles of Sox8 in testicular development and maintenance of male fertility, we have performed a detailed analysis to explore its downstream genes. We have used mRNA expression profiling to identify affected genes in Sertoli cells in the mutant testes of 2-month-old mice. Expression profiling of the heterozygous and homozygous Sox8 mutant testes indicates alterations in several important spermatogenesis and blood-testis barrier genes, providing insight into the molecular basis of the defects in Sox8(-/-) testes beyond the first wave of spermatogenesis. Copyright (C) 2009 S. Karger AG, Basel C1 [Mishina, Y.] Univ Michigan, Sch Dent, Dept Biol Mat Sci, Ann Arbor, MI 48109 USA. [Harada, S.] Merck Res Labs, Dept Bone Biol & Osteoporosis Res, West Point, PA USA. [Singh, A. P.; Mishina, Y.] Natl Inst Environm Hlth Sci, Mol Dev Biol Grp, Lab Reprod & Dev Toxicol, NIH, Res Triangle Pk, NC USA. RP Mishina, Y (reprint author), Univ Michigan, Sch Dent, Dept Biol Mat Sci, Ann Arbor, MI 48109 USA. EM mishina@umich.edu RI Singh, Ajeet/G-3935-2013 FU NIH, National Institute of Environmental Health Sciences [ES071003-11]; Indo-US Collaboration on Environment and Occupational Health Grant; RIKEN Brain Science Institute [833-3944] FX The authors would like to dedicate this manuscript to Dr. Shun Harada, a great colleague and a wonderful friend, who made significant contributions to the field of SOX biology. We gratefully thank the NIEHS Microarrays Core Facility led by Dr. Rich Paules. We thank Dr. Leping Li for sequence analyses, Drs. Mitch Eddy, Manas Ray, and Greg Scott for helpful discussion and critical reading of the manuscript. We also thank Mss. Ijeoma Nwosu, Gloria MacDonald, and Kelly McCann for their technical support, Ms. Tonya Miller for her excellent service of maintenance of the mouse colonies. This work was supported in part by the Intramural Research Program of the NIH, National Institute of Environmental Health Sciences (ES071003-11), by the Indo-US Collaboration on Environment and Occupational Health Grant, and by a gift from RIKEN Brain Science Institute (833-3944) to Y.M. NR 30 TC 8 Z9 8 U1 0 U2 0 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 1661-5425 J9 SEX DEV JI Sex. Dev. PY 2009 VL 3 IS 1 BP 16 EP 25 DI 10.1159/000200078 PG 10 WC Developmental Biology SC Developmental Biology GA 428SV UT WOS:000264871100002 PM 19339814 ER PT J AU Peterson, CH Costa-Pierce, BA Dumbauld, BR Friedman, C Hofmann, EE Kite-Powell, H Manahan, DT O'Beirn, F Paine, RT Thompson, P Whitlatch, R Roberts, S Bostrom, J Chiarello, H Mcnutt, MK Boesch, DF Corredor, JE Criddle, KR Feeley, MH Hernandez, D Holman, RA Kim, K Knuth, BA Lawson, RA Matsumoto, GI Pearlman, JS Rosenberg, AA Rudnick, DL Serafin, RJ Trehu, AM Tyack, PL Wright, DJ Yoder, JA Roberts, S Mengelt, C Park, S Bostrom, J Glickson, D Banskota, S Lewis, P Chiarello, H Justice, J AF Peterson, Charles (Pete) H. Costa-Pierce, Barry A. Dumbauld, Brett R. Friedman, Carolyn Hofmann, Eileen E. Kite-Powell, Hauke Manahan, Donal T. O'Beirn, Francis Paine, Robert T. Thompson, Paul Whitlatch, Robert Roberts, Susan Bostrom, Jodi Chiarello, Heather Mcnutt, Marcia K. Boesch, Donald F. Corredor, Jorge E. Criddle, Keith R. Feeley, Mary (Missy) H. Hernandez, Debra Holman, Robert A. Kim, Kiho Knuth, Barbara A. Lawson, Robert A. Matsumoto, George I. Pearlman, Jay S. Rosenberg, Andrew A. Rudnick, Daniel L. Serafin, Robert J. Trehu, Anne M. Tyack, Peter L. Wright, Dawn J. Yoder, James A. Roberts, Susan Mengelt, Claudia Park, Susan Bostrom, Jodi Glickson, Deborah Banskota, Shubha Lewis, Pamela Chiarello, Heather Justice, Jeremy CA Pt Reyes Natl Seashore Ocean Studies Board GP Natl Res Council TI Shellfish Mariculture in Drakes Estero, Point Reyes National Seashore, California Summary SO SHELLFISH MARICULTURE IN DRAKES ESTERO, POINT REYES NATIONAL SEASHORE, CALIFORNIA LA English DT Editorial Material; Book Chapter ID OYSTERS CRASSOSTREA-GIGAS; EELGRASS ZOSTERA-MARINA; SUBMERGED AQUATIC VEGETATION; SUSPENSION-FEEDING BIVALVES; HAPLOSPORIDIUM-NELSONI MSX; PACIFIC-NORTHWEST ESTUARY; PHOCA-VITULINA-RICHARDSI; CLIMATE-CHANGE IMPACTS; SAN-FRANCISCO BAY; HARBOR SEALS C1 [Peterson, Charles (Pete) H.] Univ N Carolina, Morehead City, NC 28557 USA. [Costa-Pierce, Barry A.] Univ Rhode Isl, Rhode Isl Sea Grant Coll Program, Narragansett, RI USA. [Costa-Pierce, Barry A.] Univ Rhode Isl, Fisheries Aquaculture & Oceanog, Narragansett, RI USA. [Dumbauld, Brett R.] ARS, USDA, Newport, OR USA. [Friedman, Carolyn] Univ Washington, Sch Aquat & Fishery Sci, Seattle, WA 98195 USA. [Hofmann, Eileen E.] Old Dominion Univ, Ctr Coastal Phys Oceanog, Oceanog, Norfolk, VA USA. [Kite-Powell, Hauke] Woods Hole Oceanog Inst, Marine Policy Ctr, Woods Hole, MA USA. [Manahan, Donal T.] Univ So Calif, Biol Sci, Los Angeles, CA USA. [O'Beirn, Francis] Inst Marine, Galway, Ireland. [Paine, Robert T.] Univ Washington, Dept Biol, Seattle, WA 98195 USA. [Thompson, Paul] Univ Aberdeen, Sch Biol Sci, Zool, Aberdeen AB9 1FX, Scotland. [Whitlatch, Robert] Univ Connecticut, Marine Sci, Groton, CT USA. [Roberts, Susan; Bostrom, Jodi; Chiarello, Heather] Ocean Studies Board, Washington, DC USA. [Roberts, Susan] Univ Calif Berkeley, Berkeley, CA 94720 USA. [Roberts, Susan] NIH, Bethesda, MD USA. [Chiarello, Heather] Natl Acad, New York, NY USA. [Mcnutt, Marcia K.; Matsumoto, George I.] Monterey Bay Aquarium Res Inst, Moss Landing, CA USA. [Boesch, Donald F.] Univ Maryland, Ctr Environm Sci, Cambridge, MD USA. [Corredor, Jorge E.] Univ Puerto Rico, Mayaguez, PR USA. [Criddle, Keith R.] Univ Alaska Fairbanks, Juneau, AK USA. [Feeley, Mary (Missy) H.] ExxonMobil Explorat Co, Houston, TX USA. [Hernandez, Debra] Hernandez & Co, Isle Of Palms, SC USA. [Holman, Robert A.; Trehu, Anne M.; Wright, Dawn J.] Oregon State Univ, Corvallis, OR 97331 USA. [Kim, Kiho] Amer Univ, Washington, DC 20016 USA. [Knuth, Barbara A.] Cornell Univ, Ithaca, NY USA. [Lawson, Robert A.] Sci Applicat Int Corp, San Diego, CA 92121 USA. [Pearlman, Jay S.] Boeing Co, Port Angeles, WA USA. [Rosenberg, Andrew A.] Univ New Hampshire, Durham, NH 03824 USA. [Rudnick, Daniel L.] Univ Calif San Diego, Scripps Inst Oceanog, La Jolla, CA 92093 USA. [Serafin, Robert J.] Natl Ctr Atmospher Res, Boulder, CO 80307 USA. [Tyack, Peter L.; Yoder, James A.] Woods Hole Oceanog Inst, Woods Hole, MA USA. RP Peterson, CH (reprint author), Univ N Carolina, Morehead City, NC 28557 USA. NR 246 TC 0 Z9 0 U1 3 U2 4 PU NATL ACADEMIES PRESS PI WASHINGTON PA 2101 CONSTITUTION AVE, WASHINGTON, DC 20418 USA BN 978-0-309-13898-7 PY 2009 BP 1 EP + PG 22 WC Ecology; Fisheries SC Environmental Sciences & Ecology; Fisheries GA BC3XK UT WOS:000352027300001 ER PT J AU Peterson, CH Costa-Pierce, BA Dumbauld, BR Friedman, C Hofmann, EE Kite-Powell, H Manahan, DT O'Beirn, F Paine, RT Thompson, P Whitlatch, R Roberts, S Bostrom, J Chiarello, H Mcnutt, MK Boesch, DF Corredor, JE Criddle, KR Feeley, MH Hernandez, D Holman, RA Kim, K Knuth, BA Lawson, RA Matsumoto, GI Pearlman, JS Rosenberg, AA Rudnick, DL Serafin, RJ Trehu, AM Tyack, PL Wright, DJ Yoder, JA Roberts, S Mengelt, C Park, S Bostrom, J Glickson, D Banskota, S Lewis, P Chiarello, H Justice, J AF Peterson, Charles (Pete) H. Costa-Pierce, Barry A. Dumbauld, Brett R. Friedman, Carolyn Hofmann, Eileen E. Kite-Powell, Hauke Manahan, Donal T. O'Beirn, Francis Paine, Robert T. Thompson, Paul Whitlatch, Robert Roberts, Susan Bostrom, Jodi Chiarello, Heather Mcnutt, Marcia K. Boesch, Donald F. Corredor, Jorge E. Criddle, Keith R. Feeley, Mary (Missy) H. Hernandez, Debra Holman, Robert A. Kim, Kiho Knuth, Barbara A. Lawson, Robert A. Matsumoto, George I. Pearlman, Jay S. Rosenberg, Andrew A. Rudnick, Daniel L. Serafin, Robert J. Trehu, Anne M. Tyack, Peter L. Wright, Dawn J. Yoder, James A. Roberts, Susan Mengelt, Claudia Park, Susan Bostrom, Jodi Glickson, Deborah Banskota, Shubha Lewis, Pamela Chiarello, Heather Justice, Jeremy CA Pt Reyes Natl Seashore Ocean Studies Board GP Natl Res Council TI Shellfish Mariculture in Drakes Estero, Point Reyes National Seashore, California Introduction to Drakes Estero SO SHELLFISH MARICULTURE IN DRAKES ESTERO, POINT REYES NATIONAL SEASHORE, CALIFORNIA LA English DT Editorial Material; Book Chapter C1 [Peterson, Charles (Pete) H.] Univ N Carolina, Morehead City, NC 28557 USA. [Costa-Pierce, Barry A.] Univ Rhode Isl, Rhode Isl Sea Grant Coll Program, Narragansett, RI USA. [Costa-Pierce, Barry A.] Univ Rhode Isl, Fisheries Aquaculture & Oceanog, Narragansett, RI USA. [Dumbauld, Brett R.] ARS, USDA, Newport, OR USA. [Friedman, Carolyn] Univ Washington, Sch Aquat & Fishery Sci, Seattle, WA 98195 USA. [Hofmann, Eileen E.] Old Dominion Univ, Ctr Coastal Phys Oceanog, Oceanog, Norfolk, VA USA. [Kite-Powell, Hauke] Woods Hole Oceanog Inst, Marine Policy Ctr, Woods Hole, MA USA. [Manahan, Donal T.] Univ So Calif, Biol Sci, Los Angeles, CA USA. [O'Beirn, Francis] Inst Marine, Galway, Ireland. [Paine, Robert T.] Univ Washington, Dept Biol, Seattle, WA 98195 USA. [Thompson, Paul] Univ Aberdeen, Sch Biol Sci, Zool, Aberdeen AB9 1FX, Scotland. [Whitlatch, Robert] Univ Connecticut, Marine Sci, Groton, CT USA. [Roberts, Susan; Bostrom, Jodi; Chiarello, Heather] Ocean Studies Board, Washington, DC USA. [Roberts, Susan] Univ Calif Berkeley, Berkeley, CA 94720 USA. [Roberts, Susan] NIH, Bethesda, MD USA. [Chiarello, Heather] Natl Acad, New York, NY USA. [Mcnutt, Marcia K.; Matsumoto, George I.] Monterey Bay Aquarium Res Inst, Moss Landing, CA USA. [Boesch, Donald F.] Univ Maryland, Ctr Environm Sci, Cambridge, MD USA. [Corredor, Jorge E.] Univ Puerto Rico, Mayaguez, PR USA. [Criddle, Keith R.] Univ Alaska Fairbanks, Juneau, AK USA. [Feeley, Mary (Missy) H.] ExxonMobil Explorat Co, Houston, TX USA. [Hernandez, Debra] Hernandez & Co, Isle Of Palms, SC USA. [Holman, Robert A.; Trehu, Anne M.; Wright, Dawn J.] Oregon State Univ, Corvallis, OR 97331 USA. [Kim, Kiho] Amer Univ, Washington, DC 20016 USA. [Knuth, Barbara A.] Cornell Univ, Ithaca, NY USA. [Lawson, Robert A.] Sci Applicat Int Corp, San Diego, CA 92121 USA. [Pearlman, Jay S.] Boeing Co, Port Angeles, WA USA. [Rosenberg, Andrew A.] Univ New Hampshire, Durham, NH 03824 USA. [Rudnick, Daniel L.] Univ Calif San Diego, Scripps Inst Oceanog, La Jolla, CA 92093 USA. [Serafin, Robert J.] Natl Ctr Atmospher Res, Boulder, CO 80307 USA. [Tyack, Peter L.; Yoder, James A.] Woods Hole Oceanog Inst, Woods Hole, MA USA. RP Peterson, CH (reprint author), Univ N Carolina, Morehead City, NC 28557 USA. NR 0 TC 0 Z9 0 U1 2 U2 2 PU NATL ACADEMIES PRESS PI WASHINGTON PA 2101 CONSTITUTION AVE, WASHINGTON, DC 20418 USA BN 978-0-309-13898-7 PY 2009 BP 9 EP 24 PG 16 WC Ecology; Fisheries SC Environmental Sciences & Ecology; Fisheries GA BC3XK UT WOS:000352027300002 ER PT J AU Peterson, CH Costa-Pierce, BA Dumbauld, BR Friedman, C Hofmann, EE Kite-Powell, H Manahan, DT O'Beirn, F Paine, RT Thompson, P Whitlatch, R Roberts, S Bostrom, J Chiarello, H Mcnutt, MK Boesch, DF Corredor, JE Criddle, KR Feeley, MH Hernandez, D Holman, RA Kim, K Knuth, BA Lawson, RA Matsumoto, GI Pearlman, JS Rosenberg, AA Rudnick, DL Serafin, RJ Trehu, AM Tyack, PL Wright, DJ Yoder, JA Roberts, S Mengelt, C Park, S Bostrom, J Glickson, D Banskota, S Lewis, P Chiarello, H Justice, J AF Peterson, Charles (Pete) H. Costa-Pierce, Barry A. Dumbauld, Brett R. Friedman, Carolyn Hofmann, Eileen E. Kite-Powell, Hauke Manahan, Donal T. O'Beirn, Francis Paine, Robert T. Thompson, Paul Whitlatch, Robert Roberts, Susan Bostrom, Jodi Chiarello, Heather Mcnutt, Marcia K. Boesch, Donald F. Corredor, Jorge E. Criddle, Keith R. Feeley, Mary (Missy) H. Hernandez, Debra Holman, Robert A. Kim, Kiho Knuth, Barbara A. Lawson, Robert A. Matsumoto, George I. Pearlman, Jay S. Rosenberg, Andrew A. Rudnick, Daniel L. Serafin, Robert J. Trehu, Anne M. Tyack, Peter L. Wright, Dawn J. Yoder, James A. Roberts, Susan Mengelt, Claudia Park, Susan Bostrom, Jodi Glickson, Deborah Banskota, Shubha Lewis, Pamela Chiarello, Heather Justice, Jeremy CA Pt Reyes Natl Seashore Ocean Studies Board GP Natl Res Council TI Benthic/Pelagic Coupling-Nutrients and Particulates SO SHELLFISH MARICULTURE IN DRAKES ESTERO, POINT REYES NATIONAL SEASHORE, CALIFORNIA LA English DT Article; Book Chapter C1 [Peterson, Charles (Pete) H.] Univ N Carolina, Morehead City, NC 28557 USA. [Costa-Pierce, Barry A.] Univ Rhode Isl, Rhode Isl Sea Grant Coll Program, Narragansett, RI USA. [Costa-Pierce, Barry A.] Univ Rhode Isl, Fisheries Aquaculture & Oceanog, Narragansett, RI USA. [Dumbauld, Brett R.] ARS, USDA, Newport, OR USA. [Friedman, Carolyn] Univ Washington, Sch Aquat & Fishery Sci, Seattle, WA 98195 USA. [Hofmann, Eileen E.] Old Dominion Univ, Ctr Coastal Phys Oceanog, Oceanog, Norfolk, VA USA. [Kite-Powell, Hauke] Woods Hole Oceanog Inst, Marine Policy Ctr, Woods Hole, MA USA. [Manahan, Donal T.] Univ So Calif, Biol Sci, Los Angeles, CA USA. [O'Beirn, Francis] Inst Marine, Galway, Ireland. [Paine, Robert T.] Univ Washington, Dept Biol, Seattle, WA 98195 USA. [Thompson, Paul] Univ Aberdeen, Sch Biol Sci, Zool, Aberdeen AB9 1FX, Scotland. [Whitlatch, Robert] Univ Connecticut, Marine Sci, Groton, CT USA. [Roberts, Susan; Bostrom, Jodi; Chiarello, Heather] Ocean Studies Board, Washington, DC USA. [Roberts, Susan] Univ Calif Berkeley, Berkeley, CA 94720 USA. [Roberts, Susan] NIH, Bethesda, MD USA. [Chiarello, Heather] Natl Acad, New York, NY USA. [Mcnutt, Marcia K.; Matsumoto, George I.] Monterey Bay Aquarium Res Inst, Moss Landing, CA USA. [Boesch, Donald F.] Univ Maryland, Ctr Environm Sci, Cambridge, MD USA. [Corredor, Jorge E.] Univ Puerto Rico, Mayaguez, PR USA. [Criddle, Keith R.] Univ Alaska Fairbanks, Juneau, AK USA. [Feeley, Mary (Missy) H.] ExxonMobil Explorat Co, Houston, TX USA. [Hernandez, Debra] Hernandez & Co, Isle Of Palms, SC USA. [Holman, Robert A.; Trehu, Anne M.; Wright, Dawn J.] Oregon State Univ, Corvallis, OR 97331 USA. [Kim, Kiho] Amer Univ, Washington, DC 20016 USA. [Knuth, Barbara A.] Cornell Univ, Ithaca, NY USA. [Lawson, Robert A.] Sci Applicat Int Corp, San Diego, CA 92121 USA. [Pearlman, Jay S.] Boeing Co, Port Angeles, WA USA. [Rosenberg, Andrew A.] Univ New Hampshire, Durham, NH 03824 USA. [Rudnick, Daniel L.] Univ Calif San Diego, Scripps Inst Oceanog, La Jolla, CA 92093 USA. [Serafin, Robert J.] Natl Ctr Atmospher Res, Boulder, CO 80307 USA. [Tyack, Peter L.; Yoder, James A.] Woods Hole Oceanog Inst, Woods Hole, MA USA. RP Peterson, CH (reprint author), Univ N Carolina, Morehead City, NC 28557 USA. NR 0 TC 0 Z9 0 U1 2 U2 2 PU NATL ACADEMIES PRESS PI WASHINGTON PA 2101 CONSTITUTION AVE, WASHINGTON, DC 20418 USA BN 978-0-309-13898-7 PY 2009 BP 25 EP 29 PG 5 WC Ecology; Fisheries SC Environmental Sciences & Ecology; Fisheries GA BC3XK UT WOS:000352027300003 ER PT J AU Peterson, CH Costa-Pierce, BA Dumbauld, BR Friedman, C Hofmann, EE Kite-Powell, H Manahan, DT O'Beirn, F Paine, RT Thompson, P Whitlatch, R Roberts, S Bostrom, J Chiarello, H Mcnutt, MK Boesch, DF Corredor, JE Criddle, KR Feeley, MH Hernandez, D Holman, RA Kim, K Knuth, BA Lawson, RA Matsumoto, GI Pearlman, JS Rosenberg, AA Rudnick, DL Serafin, RJ Trehu, AM Tyack, PL Wright, DJ Yoder, JA Roberts, S Mengelt, C Park, S Bostrom, J Glickson, D Banskota, S Lewis, P Chiarello, H Justice, J AF Peterson, Charles (Pete) H. Costa-Pierce, Barry A. Dumbauld, Brett R. Friedman, Carolyn Hofmann, Eileen E. Kite-Powell, Hauke Manahan, Donal T. O'Beirn, Francis Paine, Robert T. Thompson, Paul Whitlatch, Robert Roberts, Susan Bostrom, Jodi Chiarello, Heather Mcnutt, Marcia K. Boesch, Donald F. Corredor, Jorge E. Criddle, Keith R. Feeley, Mary (Missy) H. Hernandez, Debra Holman, Robert A. Kim, Kiho Knuth, Barbara A. Lawson, Robert A. Matsumoto, George I. Pearlman, Jay S. Rosenberg, Andrew A. Rudnick, Daniel L. Serafin, Robert J. Trehu, Anne M. Tyack, Peter L. Wright, Dawn J. Yoder, James A. Roberts, Susan Mengelt, Claudia Park, Susan Bostrom, Jodi Glickson, Deborah Banskota, Shubha Lewis, Pamela Chiarello, Heather Justice, Jeremy CA Pt Reyes Natl Seashore Ocean Studies Board GP Natl Res Council TI Eelgrass SO SHELLFISH MARICULTURE IN DRAKES ESTERO, POINT REYES NATIONAL SEASHORE, CALIFORNIA LA English DT Article; Book Chapter C1 [Peterson, Charles (Pete) H.] Univ N Carolina, Morehead City, NC 28557 USA. [Costa-Pierce, Barry A.] Univ Rhode Isl, Rhode Isl Sea Grant Coll Program, Narragansett, RI USA. [Costa-Pierce, Barry A.] Univ Rhode Isl, Fisheries Aquaculture & Oceanog, Narragansett, RI USA. [Dumbauld, Brett R.] ARS, USDA, Newport, OR USA. [Friedman, Carolyn] Univ Washington, Sch Aquat & Fishery Sci, Seattle, WA 98195 USA. [Hofmann, Eileen E.] Old Dominion Univ, Ctr Coastal Phys Oceanog, Oceanog, Norfolk, VA USA. [Kite-Powell, Hauke] Woods Hole Oceanog Inst, Marine Policy Ctr, Woods Hole, MA USA. [Manahan, Donal T.] Univ So Calif, Biol Sci, Los Angeles, CA USA. [O'Beirn, Francis] Inst Marine, Galway, Ireland. [Paine, Robert T.] Univ Washington, Dept Biol, Seattle, WA 98195 USA. [Thompson, Paul] Univ Aberdeen, Sch Biol Sci, Zool, Aberdeen AB9 1FX, Scotland. [Whitlatch, Robert] Univ Connecticut, Marine Sci, Groton, CT USA. [Roberts, Susan; Bostrom, Jodi; Chiarello, Heather] Ocean Studies Board, Washington, DC USA. [Roberts, Susan] Univ Calif Berkeley, Berkeley, CA 94720 USA. [Roberts, Susan] NIH, Bethesda, MD USA. [Chiarello, Heather] Natl Acad, New York, NY USA. [Mcnutt, Marcia K.; Matsumoto, George I.] Monterey Bay Aquarium Res Inst, Moss Landing, CA USA. [Boesch, Donald F.] Univ Maryland, Ctr Environm Sci, Cambridge, MD USA. [Corredor, Jorge E.] Univ Puerto Rico, Mayaguez, PR USA. [Criddle, Keith R.] Univ Alaska Fairbanks, Juneau, AK USA. [Feeley, Mary (Missy) H.] ExxonMobil Explorat Co, Houston, TX USA. [Hernandez, Debra] Hernandez & Co, Isle Of Palms, SC USA. [Holman, Robert A.; Trehu, Anne M.; Wright, Dawn J.] Oregon State Univ, Corvallis, OR 97331 USA. [Kim, Kiho] Amer Univ, Washington, DC 20016 USA. [Knuth, Barbara A.] Cornell Univ, Ithaca, NY USA. [Lawson, Robert A.] Sci Applicat Int Corp, San Diego, CA 92121 USA. [Pearlman, Jay S.] Boeing Co, Port Angeles, WA USA. [Rosenberg, Andrew A.] Univ New Hampshire, Durham, NH 03824 USA. [Rudnick, Daniel L.] Univ Calif San Diego, Scripps Inst Oceanog, La Jolla, CA 92093 USA. [Serafin, Robert J.] Natl Ctr Atmospher Res, Boulder, CO 80307 USA. [Tyack, Peter L.; Yoder, James A.] Woods Hole Oceanog Inst, Woods Hole, MA USA. RP Peterson, CH (reprint author), Univ N Carolina, Morehead City, NC 28557 USA. NR 0 TC 0 Z9 0 U1 2 U2 2 PU NATL ACADEMIES PRESS PI WASHINGTON PA 2101 CONSTITUTION AVE, WASHINGTON, DC 20418 USA BN 978-0-309-13898-7 PY 2009 BP 30 EP 34 PG 5 WC Ecology; Fisheries SC Environmental Sciences & Ecology; Fisheries GA BC3XK UT WOS:000352027300004 ER PT J AU Peterson, CH Costa-Pierce, BA Dumbauld, BR Friedman, C Hofmann, EE Kite-Powell, H Manahan, DT O'Beirn, F Paine, RT Thompson, P Whitlatch, R Roberts, S Bostrom, J Chiarello, H Mcnutt, MK Boesch, DF Corredor, JE Criddle, KR Feeley, MH Hernandez, D Holman, RA Kim, K Knuth, BA Lawson, RA Matsumoto, GI Pearlman, JS Rosenberg, AA Rudnick, DL Serafin, RJ Trehu, AM Tyack, PL Wright, DJ Yoder, JA Roberts, S Mengelt, C Park, S Bostrom, J Glickson, D Banskota, S Lewis, P Chiarello, H Justice, J AF Peterson, Charles (Pete) H. Costa-Pierce, Barry A. Dumbauld, Brett R. Friedman, Carolyn Hofmann, Eileen E. Kite-Powell, Hauke Manahan, Donal T. O'Beirn, Francis Paine, Robert T. Thompson, Paul Whitlatch, Robert Roberts, Susan Bostrom, Jodi Chiarello, Heather Mcnutt, Marcia K. Boesch, Donald F. Corredor, Jorge E. Criddle, Keith R. Feeley, Mary (Missy) H. Hernandez, Debra Holman, Robert A. Kim, Kiho Knuth, Barbara A. Lawson, Robert A. Matsumoto, George I. Pearlman, Jay S. Rosenberg, Andrew A. Rudnick, Daniel L. Serafin, Robert J. Trehu, Anne M. Tyack, Peter L. Wright, Dawn J. Yoder, James A. Roberts, Susan Mengelt, Claudia Park, Susan Bostrom, Jodi Glickson, Deborah Banskota, Shubha Lewis, Pamela Chiarello, Heather Justice, Jeremy CA Pt Reyes Natl Seashore Ocean Studies Board GP Natl Res Council TI Fish SO SHELLFISH MARICULTURE IN DRAKES ESTERO, POINT REYES NATIONAL SEASHORE, CALIFORNIA LA English DT Article; Book Chapter C1 [Peterson, Charles (Pete) H.] Univ N Carolina, Morehead City, NC 28557 USA. [Costa-Pierce, Barry A.] Univ Rhode Isl, Rhode Isl Sea Grant Coll Program, Narragansett, RI USA. [Costa-Pierce, Barry A.] Univ Rhode Isl, Fisheries Aquaculture & Oceanog, Narragansett, RI USA. [Dumbauld, Brett R.] ARS, USDA, Newport, OR USA. [Friedman, Carolyn] Univ Washington, Sch Aquat & Fishery Sci, Seattle, WA 98195 USA. [Hofmann, Eileen E.] Old Dominion Univ, Ctr Coastal Phys Oceanog, Oceanog, Norfolk, VA USA. [Kite-Powell, Hauke] Woods Hole Oceanog Inst, Marine Policy Ctr, Woods Hole, MA USA. [Manahan, Donal T.] Univ So Calif, Biol Sci, Los Angeles, CA USA. [O'Beirn, Francis] Inst Marine, Galway, Ireland. [Paine, Robert T.] Univ Washington, Dept Biol, Seattle, WA 98195 USA. [Thompson, Paul] Univ Aberdeen, Sch Biol Sci, Zool, Aberdeen AB9 1FX, Scotland. [Whitlatch, Robert] Univ Connecticut, Marine Sci, Groton, CT USA. [Roberts, Susan; Bostrom, Jodi; Chiarello, Heather] Ocean Studies Board, Washington, DC USA. [Roberts, Susan] Univ Calif Berkeley, Berkeley, CA 94720 USA. [Roberts, Susan] NIH, Bethesda, MD USA. [Chiarello, Heather] Natl Acad, New York, NY USA. [Mcnutt, Marcia K.; Matsumoto, George I.] Monterey Bay Aquarium Res Inst, Moss Landing, CA USA. [Boesch, Donald F.] Univ Maryland, Ctr Environm Sci, Cambridge, MD USA. [Corredor, Jorge E.] Univ Puerto Rico, Mayaguez, PR USA. [Criddle, Keith R.] Univ Alaska Fairbanks, Juneau, AK USA. [Feeley, Mary (Missy) H.] ExxonMobil Explorat Co, Houston, TX USA. [Hernandez, Debra] Hernandez & Co, Isle Of Palms, SC USA. [Holman, Robert A.; Trehu, Anne M.; Wright, Dawn J.] Oregon State Univ, Corvallis, OR 97331 USA. [Kim, Kiho] Amer Univ, Washington, DC 20016 USA. [Knuth, Barbara A.] Cornell Univ, Ithaca, NY USA. [Lawson, Robert A.] Sci Applicat Int Corp, San Diego, CA 92121 USA. [Pearlman, Jay S.] Boeing Co, Port Angeles, WA USA. [Rosenberg, Andrew A.] Univ New Hampshire, Durham, NH 03824 USA. [Rudnick, Daniel L.] Univ Calif San Diego, Scripps Inst Oceanog, La Jolla, CA 92093 USA. [Serafin, Robert J.] Natl Ctr Atmospher Res, Boulder, CO 80307 USA. [Tyack, Peter L.; Yoder, James A.] Woods Hole Oceanog Inst, Woods Hole, MA USA. RP Peterson, CH (reprint author), Univ N Carolina, Morehead City, NC 28557 USA. NR 0 TC 0 Z9 0 U1 2 U2 2 PU NATL ACADEMIES PRESS PI WASHINGTON PA 2101 CONSTITUTION AVE, WASHINGTON, DC 20418 USA BN 978-0-309-13898-7 PY 2009 BP 35 EP 37 PG 3 WC Ecology; Fisheries SC Environmental Sciences & Ecology; Fisheries GA BC3XK UT WOS:000352027300005 ER PT J AU Peterson, CH Costa-Pierce, BA Dumbauld, BR Friedman, C Hofmann, EE Kite-Powell, H Manahan, DT O'Beirn, F Paine, RT Thompson, P Whitlatch, R Roberts, S Bostrom, J Chiarello, H Mcnutt, MK Boesch, DF Corredor, JE Criddle, KR Feeley, MH Hernandez, D Holman, RA Kim, K Knuth, BA Lawson, RA Matsumoto, GI Pearlman, JS Rosenberg, AA Rudnick, DL Serafin, RJ Trehu, AM Tyack, PL Wright, DJ Yoder, JA Roberts, S Mengelt, C Park, S Bostrom, J Glickson, D Banskota, S Lewis, P Chiarello, H Justice, J AF Peterson, Charles (Pete) H. Costa-Pierce, Barry A. Dumbauld, Brett R. Friedman, Carolyn Hofmann, Eileen E. Kite-Powell, Hauke Manahan, Donal T. O'Beirn, Francis Paine, Robert T. Thompson, Paul Whitlatch, Robert Roberts, Susan Bostrom, Jodi Chiarello, Heather Mcnutt, Marcia K. Boesch, Donald F. Corredor, Jorge E. Criddle, Keith R. Feeley, Mary (Missy) H. Hernandez, Debra Holman, Robert A. Kim, Kiho Knuth, Barbara A. Lawson, Robert A. Matsumoto, George I. Pearlman, Jay S. Rosenberg, Andrew A. Rudnick, Daniel L. Serafin, Robert J. Trehu, Anne M. Tyack, Peter L. Wright, Dawn J. Yoder, James A. Roberts, Susan Mengelt, Claudia Park, Susan Bostrom, Jodi Glickson, Deborah Banskota, Shubha Lewis, Pamela Chiarello, Heather Justice, Jeremy CA Pt Reyes Natl Seashore Ocean Studies Board GP Natl Res Council TI Benthic Invertebrates in Soft Sediments SO SHELLFISH MARICULTURE IN DRAKES ESTERO, POINT REYES NATIONAL SEASHORE, CALIFORNIA LA English DT Article; Book Chapter C1 [Peterson, Charles (Pete) H.] Univ N Carolina, Morehead City, NC 28557 USA. [Costa-Pierce, Barry A.] Univ Rhode Isl, Rhode Isl Sea Grant Coll Program, Narragansett, RI USA. [Costa-Pierce, Barry A.] Univ Rhode Isl, Fisheries Aquaculture & Oceanog, Narragansett, RI USA. [Dumbauld, Brett R.] ARS, USDA, Newport, OR USA. [Friedman, Carolyn] Univ Washington, Sch Aquat & Fishery Sci, Seattle, WA 98195 USA. [Hofmann, Eileen E.] Old Dominion Univ, Ctr Coastal Phys Oceanog, Oceanog, Norfolk, VA USA. [Kite-Powell, Hauke] Woods Hole Oceanog Inst, Marine Policy Ctr, Woods Hole, MA USA. [Manahan, Donal T.] Univ So Calif, Biol Sci, Los Angeles, CA USA. [O'Beirn, Francis] Inst Marine, Galway, Ireland. [Paine, Robert T.] Univ Washington, Dept Biol, Seattle, WA 98195 USA. [Thompson, Paul] Univ Aberdeen, Sch Biol Sci, Zool, Aberdeen AB9 1FX, Scotland. [Whitlatch, Robert] Univ Connecticut, Marine Sci, Groton, CT USA. [Roberts, Susan; Bostrom, Jodi; Chiarello, Heather] Ocean Studies Board, Washington, DC USA. [Roberts, Susan] Univ Calif Berkeley, Berkeley, CA 94720 USA. [Roberts, Susan] NIH, Bethesda, MD USA. [Chiarello, Heather] Natl Acad, New York, NY USA. [Mcnutt, Marcia K.; Matsumoto, George I.] Monterey Bay Aquarium Res Inst, Moss Landing, CA USA. [Boesch, Donald F.] Univ Maryland, Ctr Environm Sci, Cambridge, MD USA. [Corredor, Jorge E.] Univ Puerto Rico, Mayaguez, PR USA. [Criddle, Keith R.] Univ Alaska Fairbanks, Juneau, AK USA. [Feeley, Mary (Missy) H.] ExxonMobil Explorat Co, Houston, TX USA. [Hernandez, Debra] Hernandez & Co, Isle Of Palms, SC USA. [Holman, Robert A.; Trehu, Anne M.; Wright, Dawn J.] Oregon State Univ, Corvallis, OR 97331 USA. [Kim, Kiho] Amer Univ, Washington, DC 20016 USA. [Knuth, Barbara A.] Cornell Univ, Ithaca, NY USA. [Lawson, Robert A.] Sci Applicat Int Corp, San Diego, CA 92121 USA. [Pearlman, Jay S.] Boeing Co, Port Angeles, WA USA. [Rosenberg, Andrew A.] Univ New Hampshire, Durham, NH 03824 USA. [Rudnick, Daniel L.] Univ Calif San Diego, Scripps Inst Oceanog, La Jolla, CA 92093 USA. [Serafin, Robert J.] Natl Ctr Atmospher Res, Boulder, CO 80307 USA. [Tyack, Peter L.; Yoder, James A.] Woods Hole Oceanog Inst, Woods Hole, MA USA. RP Peterson, CH (reprint author), Univ N Carolina, Morehead City, NC 28557 USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU NATL ACADEMIES PRESS PI WASHINGTON PA 2101 CONSTITUTION AVE, WASHINGTON, DC 20418 USA BN 978-0-309-13898-7 PY 2009 BP 38 EP 40 PG 3 WC Ecology; Fisheries SC Environmental Sciences & Ecology; Fisheries GA BC3XK UT WOS:000352027300006 ER PT J AU Peterson, CH Costa-Pierce, BA Dumbauld, BR Friedman, C Hofmann, EE Kite-Powell, H Manahan, DT O'Beirn, F Paine, RT Thompson, P Whitlatch, R Roberts, S Bostrom, J Chiarello, H Mcnutt, MK Boesch, DF Corredor, JE Criddle, KR Feeley, MH Hernandez, D Holman, RA Kim, K Knuth, BA Lawson, RA Matsumoto, GI Pearlman, JS Rosenberg, AA Rudnick, DL Serafin, RJ Trehu, AM Tyack, PL Wright, DJ Yoder, JA Roberts, S Mengelt, C Park, S Bostrom, J Glickson, D Banskota, S Lewis, P Chiarello, H Justice, J AF Peterson, Charles (Pete) H. Costa-Pierce, Barry A. Dumbauld, Brett R. Friedman, Carolyn Hofmann, Eileen E. Kite-Powell, Hauke Manahan, Donal T. O'Beirn, Francis Paine, Robert T. Thompson, Paul Whitlatch, Robert Roberts, Susan Bostrom, Jodi Chiarello, Heather Mcnutt, Marcia K. Boesch, Donald F. Corredor, Jorge E. Criddle, Keith R. Feeley, Mary (Missy) H. Hernandez, Debra Holman, Robert A. Kim, Kiho Knuth, Barbara A. Lawson, Robert A. Matsumoto, George I. Pearlman, Jay S. Rosenberg, Andrew A. Rudnick, Daniel L. Serafin, Robert J. Trehu, Anne M. Tyack, Peter L. Wright, Dawn J. Yoder, James A. Roberts, Susan Mengelt, Claudia Park, Susan Bostrom, Jodi Glickson, Deborah Banskota, Shubha Lewis, Pamela Chiarello, Heather Justice, Jeremy CA Pt Reyes Natl Seashore Ocean Studies Board GP Natl Res Council TI Harbor Seals SO SHELLFISH MARICULTURE IN DRAKES ESTERO, POINT REYES NATIONAL SEASHORE, CALIFORNIA LA English DT Article; Book Chapter C1 [Peterson, Charles (Pete) H.] Univ N Carolina, Morehead City, NC 28557 USA. [Costa-Pierce, Barry A.] Univ Rhode Isl, Rhode Isl Sea Grant Coll Program, Narragansett, RI USA. [Costa-Pierce, Barry A.] Univ Rhode Isl, Fisheries Aquaculture & Oceanog, Narragansett, RI USA. [Dumbauld, Brett R.] ARS, USDA, Newport, OR USA. [Friedman, Carolyn] Univ Washington, Sch Aquat & Fishery Sci, Seattle, WA 98195 USA. [Hofmann, Eileen E.] Old Dominion Univ, Ctr Coastal Phys Oceanog, Oceanog, Norfolk, VA USA. [Kite-Powell, Hauke] Woods Hole Oceanog Inst, Marine Policy Ctr, Woods Hole, MA USA. [Manahan, Donal T.] Univ So Calif, Biol Sci, Los Angeles, CA USA. [O'Beirn, Francis] Inst Marine, Galway, Ireland. [Paine, Robert T.] Univ Washington, Dept Biol, Seattle, WA 98195 USA. [Thompson, Paul] Univ Aberdeen, Sch Biol Sci, Zool, Aberdeen AB9 1FX, Scotland. [Whitlatch, Robert] Univ Connecticut, Marine Sci, Groton, CT USA. [Roberts, Susan; Bostrom, Jodi; Chiarello, Heather] Ocean Studies Board, Washington, DC USA. [Roberts, Susan] Univ Calif Berkeley, Berkeley, CA 94720 USA. [Roberts, Susan] NIH, Bethesda, MD USA. [Chiarello, Heather] Natl Acad, New York, NY USA. [Mcnutt, Marcia K.; Matsumoto, George I.] Monterey Bay Aquarium Res Inst, Moss Landing, CA USA. [Boesch, Donald F.] Univ Maryland, Ctr Environm Sci, Cambridge, MD USA. [Corredor, Jorge E.] Univ Puerto Rico, Mayaguez, PR USA. [Criddle, Keith R.] Univ Alaska Fairbanks, Juneau, AK USA. [Feeley, Mary (Missy) H.] ExxonMobil Explorat Co, Houston, TX USA. [Hernandez, Debra] Hernandez & Co, Isle Of Palms, SC USA. [Holman, Robert A.; Trehu, Anne M.; Wright, Dawn J.] Oregon State Univ, Corvallis, OR 97331 USA. [Kim, Kiho] Amer Univ, Washington, DC 20016 USA. [Knuth, Barbara A.] Cornell Univ, Ithaca, NY USA. [Lawson, Robert A.] Sci Applicat Int Corp, San Diego, CA 92121 USA. [Pearlman, Jay S.] Boeing Co, Port Angeles, WA USA. [Rosenberg, Andrew A.] Univ New Hampshire, Durham, NH 03824 USA. [Rudnick, Daniel L.] Univ Calif San Diego, Scripps Inst Oceanog, La Jolla, CA 92093 USA. [Serafin, Robert J.] Natl Ctr Atmospher Res, Boulder, CO 80307 USA. [Tyack, Peter L.; Yoder, James A.] Woods Hole Oceanog Inst, Woods Hole, MA USA. RP Peterson, CH (reprint author), Univ N Carolina, Morehead City, NC 28557 USA. NR 0 TC 0 Z9 0 U1 2 U2 2 PU NATL ACADEMIES PRESS PI WASHINGTON PA 2101 CONSTITUTION AVE, WASHINGTON, DC 20418 USA BN 978-0-309-13898-7 PY 2009 BP 41 EP 49 PG 9 WC Ecology; Fisheries SC Environmental Sciences & Ecology; Fisheries GA BC3XK UT WOS:000352027300007 ER PT J AU Peterson, CH Costa-Pierce, BA Dumbauld, BR Friedman, C Hofmann, EE Kite-Powell, H Manahan, DT O'Beirn, F Paine, RT Thompson, P Whitlatch, R Roberts, S Bostrom, J Chiarello, H Mcnutt, MK Boesch, DF Corredor, JE Criddle, KR Feeley, MH Hernandez, D Holman, RA Kim, K Knuth, BA Lawson, RA Matsumoto, GI Pearlman, JS Rosenberg, AA Rudnick, DL Serafin, RJ Trehu, AM Tyack, PL Wright, DJ Yoder, JA Roberts, S Mengelt, C Park, S Bostrom, J Glickson, D Banskota, S Lewis, P Chiarello, H Justice, J AF Peterson, Charles (Pete) H. Costa-Pierce, Barry A. Dumbauld, Brett R. Friedman, Carolyn Hofmann, Eileen E. Kite-Powell, Hauke Manahan, Donal T. O'Beirn, Francis Paine, Robert T. Thompson, Paul Whitlatch, Robert Roberts, Susan Bostrom, Jodi Chiarello, Heather Mcnutt, Marcia K. Boesch, Donald F. Corredor, Jorge E. Criddle, Keith R. Feeley, Mary (Missy) H. Hernandez, Debra Holman, Robert A. Kim, Kiho Knuth, Barbara A. Lawson, Robert A. Matsumoto, George I. Pearlman, Jay S. Rosenberg, Andrew A. Rudnick, Daniel L. Serafin, Robert J. Trehu, Anne M. Tyack, Peter L. Wright, Dawn J. Yoder, James A. Roberts, Susan Mengelt, Claudia Park, Susan Bostrom, Jodi Glickson, Deborah Banskota, Shubha Lewis, Pamela Chiarello, Heather Justice, Jeremy CA Pt Reyes Natl Seashore Ocean Studies Board GP Natl Res Council TI Nonnative Species SO SHELLFISH MARICULTURE IN DRAKES ESTERO, POINT REYES NATIONAL SEASHORE, CALIFORNIA LA English DT Article; Book Chapter C1 [Peterson, Charles (Pete) H.] Univ N Carolina, Morehead City, NC 28557 USA. [Costa-Pierce, Barry A.] Univ Rhode Isl, Rhode Isl Sea Grant Coll Program, Narragansett, RI USA. [Costa-Pierce, Barry A.] Univ Rhode Isl, Fisheries Aquaculture & Oceanog, Narragansett, RI USA. [Dumbauld, Brett R.] ARS, USDA, Newport, OR USA. [Friedman, Carolyn] Univ Washington, Sch Aquat & Fishery Sci, Seattle, WA 98195 USA. [Hofmann, Eileen E.] Old Dominion Univ, Ctr Coastal Phys Oceanog, Oceanog, Norfolk, VA USA. [Kite-Powell, Hauke] Woods Hole Oceanog Inst, Marine Policy Ctr, Woods Hole, MA USA. [Manahan, Donal T.] Univ So Calif, Biol Sci, Los Angeles, CA USA. [O'Beirn, Francis] Inst Marine, Galway, Ireland. [Paine, Robert T.] Univ Washington, Dept Biol, Seattle, WA 98195 USA. [Thompson, Paul] Univ Aberdeen, Sch Biol Sci, Zool, Aberdeen AB9 1FX, Scotland. [Whitlatch, Robert] Univ Connecticut, Marine Sci, Groton, CT USA. [Roberts, Susan; Bostrom, Jodi; Chiarello, Heather] Ocean Studies Board, Washington, DC USA. [Roberts, Susan] Univ Calif Berkeley, Berkeley, CA 94720 USA. [Roberts, Susan] NIH, Bethesda, MD USA. [Chiarello, Heather] Natl Acad, New York, NY USA. [Mcnutt, Marcia K.; Matsumoto, George I.] Monterey Bay Aquarium Res Inst, Moss Landing, CA USA. [Boesch, Donald F.] Univ Maryland, Ctr Environm Sci, Cambridge, MD USA. [Corredor, Jorge E.] Univ Puerto Rico, Mayaguez, PR USA. [Criddle, Keith R.] Univ Alaska Fairbanks, Juneau, AK USA. [Feeley, Mary (Missy) H.] ExxonMobil Explorat Co, Houston, TX USA. [Hernandez, Debra] Hernandez & Co, Isle Of Palms, SC USA. [Holman, Robert A.; Trehu, Anne M.; Wright, Dawn J.] Oregon State Univ, Corvallis, OR 97331 USA. [Kim, Kiho] Amer Univ, Washington, DC 20016 USA. [Knuth, Barbara A.] Cornell Univ, Ithaca, NY USA. [Lawson, Robert A.] Sci Applicat Int Corp, San Diego, CA 92121 USA. [Pearlman, Jay S.] Boeing Co, Port Angeles, WA USA. [Rosenberg, Andrew A.] Univ New Hampshire, Durham, NH 03824 USA. [Rudnick, Daniel L.] Univ Calif San Diego, Scripps Inst Oceanog, La Jolla, CA 92093 USA. [Serafin, Robert J.] Natl Ctr Atmospher Res, Boulder, CO 80307 USA. [Tyack, Peter L.; Yoder, James A.] Woods Hole Oceanog Inst, Woods Hole, MA USA. RP Peterson, CH (reprint author), Univ N Carolina, Morehead City, NC 28557 USA. NR 0 TC 0 Z9 0 U1 2 U2 2 PU NATL ACADEMIES PRESS PI WASHINGTON PA 2101 CONSTITUTION AVE, WASHINGTON, DC 20418 USA BN 978-0-309-13898-7 PY 2009 BP 50 EP 56 PG 7 WC Ecology; Fisheries SC Environmental Sciences & Ecology; Fisheries GA BC3XK UT WOS:000352027300008 ER PT J AU Peterson, CH Costa-Pierce, BA Dumbauld, BR Friedman, C Hofmann, EE Kite-Powell, H Manahan, DT O'Beirn, F Paine, RT Thompson, P Whitlatch, R Roberts, S Bostrom, J Chiarello, H Mcnutt, MK Boesch, DF Corredor, JE Criddle, KR Feeley, MH Hernandez, D Holman, RA Kim, K Knuth, BA Lawson, RA Matsumoto, GI Pearlman, JS Rosenberg, AA Rudnick, DL Serafin, RJ Trehu, AM Tyack, PL Wright, DJ Yoder, JA Roberts, S Mengelt, C Park, S Bostrom, J Glickson, D Banskota, S Lewis, P Chiarello, H Justice, J AF Peterson, Charles (Pete) H. Costa-Pierce, Barry A. Dumbauld, Brett R. Friedman, Carolyn Hofmann, Eileen E. Kite-Powell, Hauke Manahan, Donal T. O'Beirn, Francis Paine, Robert T. Thompson, Paul Whitlatch, Robert Roberts, Susan Bostrom, Jodi Chiarello, Heather Mcnutt, Marcia K. Boesch, Donald F. Corredor, Jorge E. Criddle, Keith R. Feeley, Mary (Missy) H. Hernandez, Debra Holman, Robert A. Kim, Kiho Knuth, Barbara A. Lawson, Robert A. Matsumoto, George I. Pearlman, Jay S. Rosenberg, Andrew A. Rudnick, Daniel L. Serafin, Robert J. Trehu, Anne M. Tyack, Peter L. Wright, Dawn J. Yoder, James A. Roberts, Susan Mengelt, Claudia Park, Susan Bostrom, Jodi Glickson, Deborah Banskota, Shubha Lewis, Pamela Chiarello, Heather Justice, Jeremy CA Pt Reyes Natl Seashore Ocean Studies Board GP Natl Res Council TI Birds SO SHELLFISH MARICULTURE IN DRAKES ESTERO, POINT REYES NATIONAL SEASHORE, CALIFORNIA LA English DT Article; Book Chapter C1 [Peterson, Charles (Pete) H.] Univ N Carolina, Morehead City, NC 28557 USA. [Costa-Pierce, Barry A.] Univ Rhode Isl, Rhode Isl Sea Grant Coll Program, Narragansett, RI USA. [Costa-Pierce, Barry A.] Univ Rhode Isl, Fisheries Aquaculture & Oceanog, Narragansett, RI USA. [Dumbauld, Brett R.] ARS, USDA, Newport, OR USA. [Friedman, Carolyn] Univ Washington, Sch Aquat & Fishery Sci, Seattle, WA 98195 USA. [Hofmann, Eileen E.] Old Dominion Univ, Ctr Coastal Phys Oceanog, Oceanog, Norfolk, VA USA. [Kite-Powell, Hauke] Woods Hole Oceanog Inst, Marine Policy Ctr, Woods Hole, MA USA. [Manahan, Donal T.] Univ So Calif, Biol Sci, Los Angeles, CA USA. [O'Beirn, Francis] Inst Marine, Galway, Ireland. [Paine, Robert T.] Univ Washington, Dept Biol, Seattle, WA 98195 USA. [Thompson, Paul] Univ Aberdeen, Sch Biol Sci, Zool, Aberdeen AB9 1FX, Scotland. [Whitlatch, Robert] Univ Connecticut, Marine Sci, Groton, CT USA. [Roberts, Susan; Bostrom, Jodi; Chiarello, Heather] Ocean Studies Board, Washington, DC USA. [Roberts, Susan] Univ Calif Berkeley, Berkeley, CA 94720 USA. [Roberts, Susan] NIH, Bethesda, MD USA. [Chiarello, Heather] Natl Acad, New York, NY USA. [Mcnutt, Marcia K.; Matsumoto, George I.] Monterey Bay Aquarium Res Inst, Moss Landing, CA USA. [Boesch, Donald F.] Univ Maryland, Ctr Environm Sci, Cambridge, MD USA. [Corredor, Jorge E.] Univ Puerto Rico, Mayaguez, PR USA. [Criddle, Keith R.] Univ Alaska Fairbanks, Juneau, AK USA. [Feeley, Mary (Missy) H.] ExxonMobil Explorat Co, Houston, TX USA. [Hernandez, Debra] Hernandez & Co, Isle Of Palms, SC USA. [Holman, Robert A.; Trehu, Anne M.; Wright, Dawn J.] Oregon State Univ, Corvallis, OR 97331 USA. [Kim, Kiho] Amer Univ, Washington, DC 20016 USA. [Knuth, Barbara A.] Cornell Univ, Ithaca, NY USA. [Lawson, Robert A.] Sci Applicat Int Corp, San Diego, CA 92121 USA. [Pearlman, Jay S.] Boeing Co, Port Angeles, WA USA. [Rosenberg, Andrew A.] Univ New Hampshire, Durham, NH 03824 USA. [Rudnick, Daniel L.] Univ Calif San Diego, Scripps Inst Oceanog, La Jolla, CA 92093 USA. [Serafin, Robert J.] Natl Ctr Atmospher Res, Boulder, CO 80307 USA. [Tyack, Peter L.; Yoder, James A.] Woods Hole Oceanog Inst, Woods Hole, MA USA. RP Peterson, CH (reprint author), Univ N Carolina, Morehead City, NC 28557 USA. NR 0 TC 0 Z9 0 U1 2 U2 2 PU NATL ACADEMIES PRESS PI WASHINGTON PA 2101 CONSTITUTION AVE, WASHINGTON, DC 20418 USA BN 978-0-309-13898-7 PY 2009 BP 57 EP 60 PG 4 WC Ecology; Fisheries SC Environmental Sciences & Ecology; Fisheries GA BC3XK UT WOS:000352027300009 ER PT J AU Peterson, CH Costa-Pierce, BA Dumbauld, BR Friedman, C Hofmann, EE Kite-Powell, H Manahan, DT O'Beirn, F Paine, RT Thompson, P Whitlatch, R Roberts, S Bostrom, J Chiarello, H Mcnutt, MK Boesch, DF Corredor, JE Criddle, KR Feeley, MH Hernandez, D Holman, RA Kim, K Knuth, BA Lawson, RA Matsumoto, GI Pearlman, JS Rosenberg, AA Rudnick, DL Serafin, RJ Trehu, AM Tyack, PL Wright, DJ Yoder, JA Roberts, S Mengelt, C Park, S Bostrom, J Glickson, D Banskota, S Lewis, P Chiarello, H Justice, J AF Peterson, Charles (Pete) H. Costa-Pierce, Barry A. Dumbauld, Brett R. Friedman, Carolyn Hofmann, Eileen E. Kite-Powell, Hauke Manahan, Donal T. O'Beirn, Francis Paine, Robert T. Thompson, Paul Whitlatch, Robert Roberts, Susan Bostrom, Jodi Chiarello, Heather Mcnutt, Marcia K. Boesch, Donald F. Corredor, Jorge E. Criddle, Keith R. Feeley, Mary (Missy) H. Hernandez, Debra Holman, Robert A. Kim, Kiho Knuth, Barbara A. Lawson, Robert A. Matsumoto, George I. Pearlman, Jay S. Rosenberg, Andrew A. Rudnick, Daniel L. Serafin, Robert J. Trehu, Anne M. Tyack, Peter L. Wright, Dawn J. Yoder, James A. Roberts, Susan Mengelt, Claudia Park, Susan Bostrom, Jodi Glickson, Deborah Banskota, Shubha Lewis, Pamela Chiarello, Heather Justice, Jeremy CA Pt Reyes Natl Seashore Ocean Studies Board GP Natl Res Council TI Human-Use Values-Economics, Recreation, and Aesthetics SO SHELLFISH MARICULTURE IN DRAKES ESTERO, POINT REYES NATIONAL SEASHORE, CALIFORNIA LA English DT Article; Book Chapter C1 [Peterson, Charles (Pete) H.] Univ N Carolina, Morehead City, NC 28557 USA. [Costa-Pierce, Barry A.] Univ Rhode Isl, Rhode Isl Sea Grant Coll Program, Narragansett, RI USA. [Costa-Pierce, Barry A.] Univ Rhode Isl, Fisheries Aquaculture & Oceanog, Narragansett, RI USA. [Dumbauld, Brett R.] ARS, USDA, Newport, OR USA. [Friedman, Carolyn] Univ Washington, Sch Aquat & Fishery Sci, Seattle, WA 98195 USA. [Hofmann, Eileen E.] Old Dominion Univ, Ctr Coastal Phys Oceanog, Oceanog, Norfolk, VA USA. [Kite-Powell, Hauke] Woods Hole Oceanog Inst, Marine Policy Ctr, Woods Hole, MA USA. [Manahan, Donal T.] Univ So Calif, Biol Sci, Los Angeles, CA USA. [O'Beirn, Francis] Inst Marine, Galway, Ireland. [Paine, Robert T.] Univ Washington, Dept Biol, Seattle, WA 98195 USA. [Thompson, Paul] Univ Aberdeen, Sch Biol Sci, Zool, Aberdeen AB9 1FX, Scotland. [Whitlatch, Robert] Univ Connecticut, Marine Sci, Groton, CT USA. [Roberts, Susan; Bostrom, Jodi; Chiarello, Heather] Ocean Studies Board, Washington, DC USA. [Roberts, Susan] Univ Calif Berkeley, Berkeley, CA 94720 USA. [Roberts, Susan] NIH, Bethesda, MD USA. [Chiarello, Heather] Natl Acad, New York, NY USA. [Mcnutt, Marcia K.; Matsumoto, George I.] Monterey Bay Aquarium Res Inst, Moss Landing, CA USA. [Boesch, Donald F.] Univ Maryland, Ctr Environm Sci, Cambridge, MD USA. [Corredor, Jorge E.] Univ Puerto Rico, Mayaguez, PR USA. [Criddle, Keith R.] Univ Alaska Fairbanks, Juneau, AK USA. [Feeley, Mary (Missy) H.] ExxonMobil Explorat Co, Houston, TX USA. [Hernandez, Debra] Hernandez & Co, Isle Of Palms, SC USA. [Holman, Robert A.; Trehu, Anne M.; Wright, Dawn J.] Oregon State Univ, Corvallis, OR 97331 USA. [Kim, Kiho] Amer Univ, Washington, DC 20016 USA. [Knuth, Barbara A.] Cornell Univ, Ithaca, NY USA. [Lawson, Robert A.] Sci Applicat Int Corp, San Diego, CA 92121 USA. [Pearlman, Jay S.] Boeing Co, Port Angeles, WA USA. [Rosenberg, Andrew A.] Univ New Hampshire, Durham, NH 03824 USA. [Rudnick, Daniel L.] Univ Calif San Diego, Scripps Inst Oceanog, La Jolla, CA 92093 USA. [Serafin, Robert J.] Natl Ctr Atmospher Res, Boulder, CO 80307 USA. [Tyack, Peter L.; Yoder, James A.] Woods Hole Oceanog Inst, Woods Hole, MA USA. RP Peterson, CH (reprint author), Univ N Carolina, Morehead City, NC 28557 USA. NR 0 TC 0 Z9 0 U1 2 U2 2 PU NATL ACADEMIES PRESS PI WASHINGTON PA 2101 CONSTITUTION AVE, WASHINGTON, DC 20418 USA BN 978-0-309-13898-7 PY 2009 BP 61 EP 66 PG 6 WC Ecology; Fisheries SC Environmental Sciences & Ecology; Fisheries GA BC3XK UT WOS:000352027300010 ER PT J AU Peterson, CH Costa-Pierce, BA Dumbauld, BR Friedman, C Hofmann, EE Kite-Powell, H Manahan, DT O'Beirn, F Paine, RT Thompson, P Whitlatch, R Roberts, S Bostrom, J Chiarello, H Mcnutt, MK Boesch, DF Corredor, JE Criddle, KR Feeley, MH Hernandez, D Holman, RA Kim, K Knuth, BA Lawson, RA Matsumoto, GI Pearlman, JS Rosenberg, AA Rudnick, DL Serafin, RJ Trehu, AM Tyack, PL Wright, DJ Yoder, JA Roberts, S Mengelt, C Park, S Bostrom, J Glickson, D Banskota, S Lewis, P Chiarello, H Justice, J AF Peterson, Charles (Pete) H. Costa-Pierce, Barry A. Dumbauld, Brett R. Friedman, Carolyn Hofmann, Eileen E. Kite-Powell, Hauke Manahan, Donal T. O'Beirn, Francis Paine, Robert T. Thompson, Paul Whitlatch, Robert Roberts, Susan Bostrom, Jodi Chiarello, Heather Mcnutt, Marcia K. Boesch, Donald F. Corredor, Jorge E. Criddle, Keith R. Feeley, Mary (Missy) H. Hernandez, Debra Holman, Robert A. Kim, Kiho Knuth, Barbara A. Lawson, Robert A. Matsumoto, George I. Pearlman, Jay S. Rosenberg, Andrew A. Rudnick, Daniel L. Serafin, Robert J. Trehu, Anne M. Tyack, Peter L. Wright, Dawn J. Yoder, James A. Roberts, Susan Mengelt, Claudia Park, Susan Bostrom, Jodi Glickson, Deborah Banskota, Shubha Lewis, Pamela Chiarello, Heather Justice, Jeremy CA Pt Reyes Natl Seashore Ocean Studies Board GP Natl Res Council TI Scientific Conclusions That Can Be Drawn SO SHELLFISH MARICULTURE IN DRAKES ESTERO, POINT REYES NATIONAL SEASHORE, CALIFORNIA LA English DT Article; Book Chapter C1 [Peterson, Charles (Pete) H.] Univ N Carolina, Morehead City, NC 28557 USA. [Costa-Pierce, Barry A.] Univ Rhode Isl, Rhode Isl Sea Grant Coll Program, Narragansett, RI USA. [Costa-Pierce, Barry A.] Univ Rhode Isl, Fisheries Aquaculture & Oceanog, Narragansett, RI USA. [Dumbauld, Brett R.] ARS, USDA, Newport, OR USA. [Friedman, Carolyn] Univ Washington, Sch Aquat & Fishery Sci, Seattle, WA 98195 USA. [Hofmann, Eileen E.] Old Dominion Univ, Ctr Coastal Phys Oceanog, Oceanog, Norfolk, VA USA. [Kite-Powell, Hauke] Woods Hole Oceanog Inst, Marine Policy Ctr, Woods Hole, MA USA. [Manahan, Donal T.] Univ So Calif, Biol Sci, Los Angeles, CA USA. [O'Beirn, Francis] Inst Marine, Galway, Ireland. [Paine, Robert T.] Univ Washington, Dept Biol, Seattle, WA 98195 USA. [Thompson, Paul] Univ Aberdeen, Sch Biol Sci, Zool, Aberdeen AB9 1FX, Scotland. [Whitlatch, Robert] Univ Connecticut, Marine Sci, Groton, CT USA. [Roberts, Susan; Bostrom, Jodi; Chiarello, Heather] Ocean Studies Board, Washington, DC USA. [Roberts, Susan] Univ Calif Berkeley, Berkeley, CA 94720 USA. [Roberts, Susan] NIH, Bethesda, MD USA. [Chiarello, Heather] Natl Acad, New York, NY USA. [Mcnutt, Marcia K.; Matsumoto, George I.] Monterey Bay Aquarium Res Inst, Moss Landing, CA USA. [Boesch, Donald F.] Univ Maryland, Ctr Environm Sci, Cambridge, MD USA. [Corredor, Jorge E.] Univ Puerto Rico, Mayaguez, PR USA. [Criddle, Keith R.] Univ Alaska Fairbanks, Juneau, AK USA. [Feeley, Mary (Missy) H.] ExxonMobil Explorat Co, Houston, TX USA. [Hernandez, Debra] Hernandez & Co, Isle Of Palms, SC USA. [Holman, Robert A.; Trehu, Anne M.; Wright, Dawn J.] Oregon State Univ, Corvallis, OR 97331 USA. [Kim, Kiho] Amer Univ, Washington, DC 20016 USA. [Knuth, Barbara A.] Cornell Univ, Ithaca, NY USA. [Lawson, Robert A.] Sci Applicat Int Corp, San Diego, CA 92121 USA. [Pearlman, Jay S.] Boeing Co, Port Angeles, WA USA. [Rosenberg, Andrew A.] Univ New Hampshire, Durham, NH 03824 USA. [Rudnick, Daniel L.] Univ Calif San Diego, Scripps Inst Oceanog, La Jolla, CA 92093 USA. [Serafin, Robert J.] Natl Ctr Atmospher Res, Boulder, CO 80307 USA. [Tyack, Peter L.; Yoder, James A.] Woods Hole Oceanog Inst, Woods Hole, MA USA. RP Peterson, CH (reprint author), Univ N Carolina, Morehead City, NC 28557 USA. NR 0 TC 0 Z9 0 U1 2 U2 2 PU NATL ACADEMIES PRESS PI WASHINGTON PA 2101 CONSTITUTION AVE, WASHINGTON, DC 20418 USA BN 978-0-309-13898-7 PY 2009 BP 67 EP 70 PG 4 WC Ecology; Fisheries SC Environmental Sciences & Ecology; Fisheries GA BC3XK UT WOS:000352027300011 ER PT J AU Peterson, CH Costa-Pierce, BA Dumbauld, BR Friedman, C Hofmann, EE Kite-Powell, H Manahan, DT O'Beirn, F Paine, RT Thompson, P Whitlatch, R Roberts, S Bostrom, J Chiarello, H Mcnutt, MK Boesch, DF Corredor, JE Criddle, KR Feeley, MH Hernandez, D Holman, RA Kim, K Knuth, BA Lawson, RA Matsumoto, GI Pearlman, JS Rosenberg, AA Rudnick, DL Serafin, RJ Trehu, AM Tyack, PL Wright, DJ Yoder, JA Roberts, S Mengelt, C Park, S Bostrom, J Glickson, D Banskota, S Lewis, P Chiarello, H Justice, J AF Peterson, Charles (Pete) H. Costa-Pierce, Barry A. Dumbauld, Brett R. Friedman, Carolyn Hofmann, Eileen E. Kite-Powell, Hauke Manahan, Donal T. O'Beirn, Francis Paine, Robert T. Thompson, Paul Whitlatch, Robert Roberts, Susan Bostrom, Jodi Chiarello, Heather Mcnutt, Marcia K. Boesch, Donald F. Corredor, Jorge E. Criddle, Keith R. Feeley, Mary (Missy) H. Hernandez, Debra Holman, Robert A. Kim, Kiho Knuth, Barbara A. Lawson, Robert A. Matsumoto, George I. Pearlman, Jay S. Rosenberg, Andrew A. Rudnick, Daniel L. Serafin, Robert J. Trehu, Anne M. Tyack, Peter L. Wright, Dawn J. Yoder, James A. Roberts, Susan Mengelt, Claudia Park, Susan Bostrom, Jodi Glickson, Deborah Banskota, Shubha Lewis, Pamela Chiarello, Heather Justice, Jeremy CA Pt Reyes Natl Seashore Ocean Studies Board GP Natl Res Council TI Accuracy of the Scientific Conclusions Released by NPS to the Public SO SHELLFISH MARICULTURE IN DRAKES ESTERO, POINT REYES NATIONAL SEASHORE, CALIFORNIA LA English DT Article; Book Chapter C1 [Peterson, Charles (Pete) H.] Univ N Carolina, Morehead City, NC 28557 USA. [Costa-Pierce, Barry A.] Univ Rhode Isl, Rhode Isl Sea Grant Coll Program, Narragansett, RI USA. [Costa-Pierce, Barry A.] Univ Rhode Isl, Fisheries Aquaculture & Oceanog, Narragansett, RI USA. [Dumbauld, Brett R.] ARS, USDA, Newport, OR USA. [Friedman, Carolyn] Univ Washington, Sch Aquat & Fishery Sci, Seattle, WA 98195 USA. [Hofmann, Eileen E.] Old Dominion Univ, Ctr Coastal Phys Oceanog, Oceanog, Norfolk, VA USA. [Kite-Powell, Hauke] Woods Hole Oceanog Inst, Marine Policy Ctr, Woods Hole, MA USA. [Manahan, Donal T.] Univ So Calif, Biol Sci, Los Angeles, CA USA. [O'Beirn, Francis] Inst Marine, Galway, Ireland. [Paine, Robert T.] Univ Washington, Dept Biol, Seattle, WA 98195 USA. [Thompson, Paul] Univ Aberdeen, Sch Biol Sci, Zool, Aberdeen AB9 1FX, Scotland. [Whitlatch, Robert] Univ Connecticut, Marine Sci, Groton, CT USA. [Roberts, Susan; Bostrom, Jodi; Chiarello, Heather] Ocean Studies Board, Washington, DC USA. [Roberts, Susan] Univ Calif Berkeley, Berkeley, CA 94720 USA. [Roberts, Susan] NIH, Bethesda, MD USA. [Chiarello, Heather] Natl Acad, New York, NY USA. [Mcnutt, Marcia K.; Matsumoto, George I.] Monterey Bay Aquarium Res Inst, Moss Landing, CA USA. [Boesch, Donald F.] Univ Maryland, Ctr Environm Sci, Cambridge, MD USA. [Corredor, Jorge E.] Univ Puerto Rico, Mayaguez, PR USA. [Criddle, Keith R.] Univ Alaska Fairbanks, Juneau, AK USA. [Feeley, Mary (Missy) H.] ExxonMobil Explorat Co, Houston, TX USA. [Hernandez, Debra] Hernandez & Co, Isle Of Palms, SC USA. [Holman, Robert A.; Trehu, Anne M.; Wright, Dawn J.] Oregon State Univ, Corvallis, OR 97331 USA. [Kim, Kiho] Amer Univ, Washington, DC 20016 USA. [Knuth, Barbara A.] Cornell Univ, Ithaca, NY USA. [Lawson, Robert A.] Sci Applicat Int Corp, San Diego, CA 92121 USA. [Pearlman, Jay S.] Boeing Co, Port Angeles, WA USA. [Rosenberg, Andrew A.] Univ New Hampshire, Durham, NH 03824 USA. [Rudnick, Daniel L.] Univ Calif San Diego, Scripps Inst Oceanog, La Jolla, CA 92093 USA. [Serafin, Robert J.] Natl Ctr Atmospher Res, Boulder, CO 80307 USA. [Tyack, Peter L.; Yoder, James A.] Woods Hole Oceanog Inst, Woods Hole, MA USA. RP Peterson, CH (reprint author), Univ N Carolina, Morehead City, NC 28557 USA. NR 0 TC 0 Z9 0 U1 2 U2 2 PU NATL ACADEMIES PRESS PI WASHINGTON PA 2101 CONSTITUTION AVE, WASHINGTON, DC 20418 USA BN 978-0-309-13898-7 PY 2009 BP 71 EP 79 PG 9 WC Ecology; Fisheries SC Environmental Sciences & Ecology; Fisheries GA BC3XK UT WOS:000352027300012 ER PT J AU Peterson, CH Costa-Pierce, BA Dumbauld, BR Friedman, C Hofmann, EE Kite-Powell, H Manahan, DT O'Beirn, F Paine, RT Thompson, P Whitlatch, R Roberts, S Bostrom, J Chiarello, H Mcnutt, MK Boesch, DF Corredor, JE Criddle, KR Feeley, MH Hernandez, D Holman, RA Kim, K Knuth, BA Lawson, RA Matsumoto, GI Pearlman, JS Rosenberg, AA Rudnick, DL Serafin, RJ Trehu, AM Tyack, PL Wright, DJ Yoder, JA Roberts, S Mengelt, C Park, S Bostrom, J Glickson, D Banskota, S Lewis, P Chiarello, H Justice, J AF Peterson, Charles (Pete) H. Costa-Pierce, Barry A. Dumbauld, Brett R. Friedman, Carolyn Hofmann, Eileen E. Kite-Powell, Hauke Manahan, Donal T. O'Beirn, Francis Paine, Robert T. Thompson, Paul Whitlatch, Robert Roberts, Susan Bostrom, Jodi Chiarello, Heather Mcnutt, Marcia K. Boesch, Donald F. Corredor, Jorge E. Criddle, Keith R. Feeley, Mary (Missy) H. Hernandez, Debra Holman, Robert A. Kim, Kiho Knuth, Barbara A. Lawson, Robert A. Matsumoto, George I. Pearlman, Jay S. Rosenberg, Andrew A. Rudnick, Daniel L. Serafin, Robert J. Trehu, Anne M. Tyack, Peter L. Wright, Dawn J. Yoder, James A. Roberts, Susan Mengelt, Claudia Park, Susan Bostrom, Jodi Glickson, Deborah Banskota, Shubha Lewis, Pamela Chiarello, Heather Justice, Jeremy CA Pt Reyes Natl Seashore Ocean Studies Board GP Natl Res Council TI How Scientific Conclusions Affected NPS Decision Making SO SHELLFISH MARICULTURE IN DRAKES ESTERO, POINT REYES NATIONAL SEASHORE, CALIFORNIA LA English DT Article; Book Chapter C1 [Peterson, Charles (Pete) H.] Univ N Carolina, Morehead City, NC 28557 USA. [Costa-Pierce, Barry A.] Univ Rhode Isl, Rhode Isl Sea Grant Coll Program, Narragansett, RI USA. [Costa-Pierce, Barry A.] Univ Rhode Isl, Fisheries Aquaculture & Oceanog, Narragansett, RI USA. [Dumbauld, Brett R.] ARS, USDA, Newport, OR USA. [Friedman, Carolyn] Univ Washington, Sch Aquat & Fishery Sci, Seattle, WA 98195 USA. [Hofmann, Eileen E.] Old Dominion Univ, Ctr Coastal Phys Oceanog, Oceanog, Norfolk, VA USA. [Kite-Powell, Hauke] Woods Hole Oceanog Inst, Marine Policy Ctr, Woods Hole, MA USA. [Manahan, Donal T.] Univ So Calif, Biol Sci, Los Angeles, CA USA. [O'Beirn, Francis] Inst Marine, Galway, Ireland. [Paine, Robert T.] Univ Washington, Dept Biol, Seattle, WA 98195 USA. [Thompson, Paul] Univ Aberdeen, Sch Biol Sci, Zool, Aberdeen AB9 1FX, Scotland. [Whitlatch, Robert] Univ Connecticut, Marine Sci, Groton, CT USA. [Roberts, Susan; Bostrom, Jodi; Chiarello, Heather] Ocean Studies Board, Washington, DC USA. [Roberts, Susan] Univ Calif Berkeley, Berkeley, CA 94720 USA. [Roberts, Susan] NIH, Bethesda, MD USA. [Chiarello, Heather] Natl Acad, New York, NY USA. [Mcnutt, Marcia K.; Matsumoto, George I.] Monterey Bay Aquarium Res Inst, Moss Landing, CA USA. [Boesch, Donald F.] Univ Maryland, Ctr Environm Sci, Cambridge, MD USA. [Corredor, Jorge E.] Univ Puerto Rico, Mayaguez, PR USA. [Criddle, Keith R.] Univ Alaska Fairbanks, Juneau, AK USA. [Feeley, Mary (Missy) H.] ExxonMobil Explorat Co, Houston, TX USA. [Hernandez, Debra] Hernandez & Co, Isle Of Palms, SC USA. [Holman, Robert A.; Trehu, Anne M.; Wright, Dawn J.] Oregon State Univ, Corvallis, OR 97331 USA. [Kim, Kiho] Amer Univ, Washington, DC 20016 USA. [Knuth, Barbara A.] Cornell Univ, Ithaca, NY USA. [Lawson, Robert A.] Sci Applicat Int Corp, San Diego, CA 92121 USA. [Pearlman, Jay S.] Boeing Co, Port Angeles, WA USA. [Rosenberg, Andrew A.] Univ New Hampshire, Durham, NH 03824 USA. [Rudnick, Daniel L.] Univ Calif San Diego, Scripps Inst Oceanog, La Jolla, CA 92093 USA. [Serafin, Robert J.] Natl Ctr Atmospher Res, Boulder, CO 80307 USA. [Tyack, Peter L.; Yoder, James A.] Woods Hole Oceanog Inst, Woods Hole, MA USA. RP Peterson, CH (reprint author), Univ N Carolina, Morehead City, NC 28557 USA. NR 0 TC 0 Z9 0 U1 2 U2 2 PU NATL ACADEMIES PRESS PI WASHINGTON PA 2101 CONSTITUTION AVE, WASHINGTON, DC 20418 USA BN 978-0-309-13898-7 PY 2009 BP 80 EP 87 PG 8 WC Ecology; Fisheries SC Environmental Sciences & Ecology; Fisheries GA BC3XK UT WOS:000352027300013 ER PT J AU Goel, P Sherman, A AF Goel, Pranay Sherman, Arthur TI The Geometry of Bursting in the Dual Oscillator Model of Pancreatic beta-cells SO SIAM JOURNAL ON APPLIED DYNAMICAL SYSTEMS LA English DT Article DE bursting; oscillations; calcium; insulin; pancreatic beta-cells; sliding bars; dual oscillator model; composite bifurcation diagram; fast-slow systems; coupled oscillators ID ELECTRICAL-ACTIVITY; INSULIN-SECRETION; CALCIUM; ISLETS; MEMBRANE; RETICULUM AB We describe an extended fast-slow analysis for the dual oscillator model (DOM) for bursting oscillations in pancreatic beta-cells, which occur on a wide range of time scales, from seconds to minutes. This wide dynamic range has been suggested to result from the interactions of a very slow metabolic, possibly glycolytic, oscillator and a faster electrical oscillator, itself containing several negative feedback mechanisms with a range of time scales. Although the high dimensionality of the slow subsystem would defeat a straightforward fast-slow analysis, we show that an approximate geometrical analysis that exploits particular features of the DOM and is based on superimposing the bifurcation diagrams of the component oscillators leads to new insights into the functioning of the system. C1 [Goel, Pranay; Sherman, Arthur] Natl Inst Hlth, Bethesda, MD 20892 USA. RP Goel, P (reprint author), Natl Inst Hlth, 9000 Rockville Pike, Bethesda, MD 20892 USA. EM pgoel@iiserpune.ac.in; asherman@nih.gov RI Goel, Pranay/D-1081-2013; OI Goel, Pranay/0000-0002-2249-0288 FU NIH [R01-DK-46409B] FX We thank Bard Ermentrout and Brad Peercy for useful discussions, and Richard Bertram and Les Satin for comments on the manuscript. This theoretical work was made possible by experiments performed in the laboratory of Dr. Leslie Satin, supported by NIH grant R01-DK-46409B. NR 31 TC 12 Z9 12 U1 1 U2 2 PU SIAM PUBLICATIONS PI PHILADELPHIA PA 3600 UNIV CITY SCIENCE CENTER, PHILADELPHIA, PA 19104-2688 USA SN 1536-0040 J9 SIAM J APPL DYN SYST JI SIAM J. Appl. Dyn. Syst. PY 2009 VL 8 IS 4 BP 1664 EP 1693 DI 10.1137/08074427X PG 30 WC Mathematics, Applied; Physics, Mathematical SC Mathematics; Physics GA 518VN UT WOS:000271723300008 ER PT J AU Norian, JM Levens, ED DeCherney, AH Adamson, GD AF Norian, John M. Levens, Eric D. DeCherney, Alan H. Adamson, G. David BE Gerris, J Adamson, GD DeSutter, P Racowsky, C TI An American perspective on single embryo transfer SO SINGLE EMBRYO TRANSFER LA English DT Article; Book Chapter ID IN-VITRO FERTILIZATION; ASSISTED REPRODUCTIVE TECHNOLOGIES; RANDOMIZED CONTROLLED-TRIAL; PREIMPLANTATION GENETIC DIAGNOSIS; INTRACYTOPLASMIC SPERM INJECTION; MULTIPLE-GESTATION PREGNANCIES; LOW-BIRTH-WEIGHT; BLASTOCYST TRANSFER; CONGENITAL-MALFORMATIONS; UNITED-STATES C1 [Norian, John M.; Levens, Eric D.; DeCherney, Alan H.] NICHHD, Reprod Biol & Med Branch, NIH, Bethesda, MD 20892 USA. [Adamson, G. David] Fertil Phys No Calif, Palo Alto, CA USA. RP Norian, JM (reprint author), NICHHD, Reprod Biol & Med Branch, NIH, Bethesda, MD 20892 USA. NR 87 TC 0 Z9 0 U1 0 U2 0 PU CAMBRIDGE UNIV PRESS PI CAMBRIDGE PA THE PITT BUILDING, TRUMPINGTON ST, CAMBRIDGE CB2 1RP, CAMBS, ENGLAND BN 978-0-521-88834-9 PY 2009 BP 269 EP 281 PG 13 WC Obstetrics & Gynecology; Reproductive Biology SC Obstetrics & Gynecology; Reproductive Biology GA BDN18 UT WOS:000313966300028 ER PT S AU Hunt, R Sauna, ZE Ambudkar, SV Gottesman, MM Kimchi-Sarfaty, C AF Hunt, Ryan Sauna, Zuben E. Ambudkar, Suresh V. Gottesman, Michael M. Kimchi-Sarfaty, Chava BE Komar, AA TI Silent (Synonymous) SNPs: Should We Care About Them? SO SINGLE NUCLEOTIDE POLYMORPHISMS: METHODS AND PROTOCOLS, SECOND EDITION SE Methods in Molecular Biology LA English DT Article; Book Chapter DE Single nucleotide polymorphism; messenger RNA splicing; messenger RNA stability; messenger RNA structure; protein folding; synonymous mutations; nonsynonymous mutations; codon frequency; codon usage ID SINGLE-NUCLEOTIDE POLYMORPHISMS; MESSENGER-RNA STABILITY; SEQUENCE EVOLUTION; CODON USAGE; PROTEIN; GENE; MUTATIONS; SCHIZOPHRENIA; POPULATION; EXPRESSION AB One of the surprising findings of the Human Genome Project was that single nucleotide polymorphisms (SNPs), which, by definition, have a minor allele frequency greater than 1%, occur at higher rates than previously suspected. When occurring in the gene coding regions, SNPs can be synonymous (i.e., not causing a change in the amino acid) or nonsynonymous (when the amino acid is altered). It has long been assumed that synonymous SNPs arc inconsequential, as the primary sequence of the protein is retained. A number of studies have questioned this assumption over the last decade, shoving that synonymous mutations arc also under evolutionary pressure and they can be implicated in disease. More importantly, several of the mechanisms by which synonymous mutations alter the structure, function, and expression level of proteins are now being elucidated. Studies have demonstrated that synonymous polymorphisms can affect messenger RNA splicing, stability, and structure as well as protein folding. These changes can have a significant effect on the function of proteins, change cellular response to therapeutic targets, and often explain the different responses of individual patients to a certain medication. C1 [Hunt, Ryan; Sauna, Zuben E.; Kimchi-Sarfaty, Chava] US FDA, Lab Hemostasis, Div Hematol, Ctr Biol Evaluat & Res, Bethesda, MD 20014 USA. [Ambudkar, Suresh V.; Gottesman, Michael M.] NCI, Cell Biol Lab, NIH, Bethesda, MD 20892 USA. RP Hunt, R (reprint author), US FDA, Lab Hemostasis, Div Hematol, Ctr Biol Evaluat & Res, Bethesda, MD 20014 USA. FU Intramural NIH HHS NR 56 TC 88 Z9 96 U1 0 U2 6 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DR, STE 208, TOTOWA, NJ 07512-1165 USA SN 1064-3745 BN 978-1-60327-410-4 J9 METHODS MOL BIOL JI Methods Mol. Biol. PY 2009 VL 578 BP 23 EP 39 DI 10.1007/978-1-60327-411-1_2 D2 10.1007/978-1-60327-411-1 PG 17 WC Biochemical Research Methods; Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA BNM36 UT WOS:000274946200002 PM 19768585 ER PT J AU Buckley, A Jennison, K Buckley, J Spence, S Thurm, A Fasano, R Sato, S Susan, S AF Buckley, A. Jennison, K. Buckley, J. Spence, S. Thurm, A. Fasano, R. Sato, S. Susan, S. TI POLYSOMNOGRAPHIC ABNORMALITIES AND PARENT REPORT IN YOUNG CHILDREN WITH AUTISM SO SLEEP LA English DT Meeting Abstract CT 23rd Annual Meeting of the Associated-Professional-Sleep-Societies CY JUN 06-11, 2009 CL Seattle, WA SP Associated Profess Sleep Soc C1 [Buckley, A.; Jennison, K.; Spence, S.; Thurm, A.; Susan, S.] NIMH, Pediat & Dev Neuropsychiat Branch, Bethesda, MD 20892 USA. [Buckley, J.] NYU, Steihardt Sch Culture Educ & Human Dev, Dept Humanities & Social Sci, New York, NY USA. [Fasano, R.; Sato, S.] Natl Inst Neurol Dis, EEG Sect, Bethesda, MD USA. NR 0 TC 1 Z9 1 U1 0 U2 2 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 2009 VL 32 MA 1079 BP A352 EP A352 PG 1 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 438FT UT WOS:000265542001426 ER PT J AU Chen, T Wilk, JB O'Connor, GT Gottlieb, DJ AF Chen, T. Wilk, J. B. O'Connor, G. T. Gottlieb, D. J. TI GENETICS OF SLEEP PHENOTYPES IN THE NHLBI'S FRAMINGHAM HEART STUDY OFFSPRING COHORT SO SLEEP LA English DT Meeting Abstract CT 23rd Annual Meeting of the Associated-Professional-Sleep-Societies CY JUN 06-11, 2009 CL Seattle, WA SP Associated Profess Sleep Soc C1 [Gottlieb, D. J.] Vet Affairs Boston Healthcare Syst, Boston, MA USA. [O'Connor, G. T.; Gottlieb, D. J.] NHLBI, Framingham Heart Study, Framingham, MA USA. [Chen, T.; O'Connor, G. T.; Gottlieb, D. J.] Boston Univ, Dept Med, Sect Pulm Allergy & Crit Care, Boston, MA 02215 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 2009 VL 32 MA 1226 BP A401 EP A401 PG 1 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 438FT UT WOS:000265542001572 ER PT J AU Coddington, N Carr, W Picchioni, D Horovitz, SG Fukunaga, M Duyn, JH Braun, AR Balkin, TJ AF Coddington, N. Carr, W. Picchioni, D. Horovitz, S. G. Fukunaga, M. Duyn, J. H. Braun, A. R. Balkin, T. J. TI ACTIVATION DIFFERENCES DURING ASCENDING AND DESCENDING TRENDS IN A-WAVE POWER WHILE SLEEPING SO SLEEP LA English DT Meeting Abstract CT 23rd Annual Meeting of the Associated-Professional-Sleep-Societies CY JUN 06-11, 2009 CL Seattle, WA SP Associated Profess Sleep Soc C1 [Coddington, N.] Thomas Jefferson High Sch Sci & Technol, Alexandria, VA USA. [Coddington, N.; Carr, W.] USN, Med Res Ctr, Silver Spring, MI USA. [Carr, W.; Picchioni, D.; Braun, A. R.] Natl Inst Deafness & Other Commun Disorders, Bethesda, MD USA. [Picchioni, D.; Balkin, T. J.] Walter Reed Army Inst Res, Silver Spring, MD USA. [Horovitz, S. G.; Fukunaga, M.; Duyn, J. H.] Natl Inst Neurol Disorders & Stroke, Bethesda, MD USA. RI Duyn, Jozef/F-2483-2010 NR 0 TC 0 Z9 0 U1 0 U2 0 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 2009 VL 32 MA 0061 BP A20 EP A20 PG 1 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 438FT UT WOS:000265542000063 ER PT J AU Picchioni, D Horovitz, SG Fukunaga, M Carr, WS Balkin, TJ Duyn, JH Braun, AR AF Picchioni, D. Horovitz, S. G. Fukunaga, M. Carr, W. S. Balkin, T. J. Duyn, J. H. Braun, A. R. TI HOW SLOW CAN YOU GO? UNIQUE FMRI CORRELATIONS WITH EEG ACTIVITY BELOW 0.1 HZ DURING SLEEP SO SLEEP LA English DT Meeting Abstract CT 23rd Annual Meeting of the Associated-Professional-Sleep-Societies CY JUN 06-11, 2009 CL Seattle, WA SP Associated Profess Sleep Soc C1 [Picchioni, D.; Balkin, T. J.] Walter Reed Army Inst Res, Silver Spring, MD USA. [Horovitz, S. G.; Fukunaga, M.; Duyn, J. H.; Braun, A. R.] NIH, Bethesda, MD 20892 USA. [Carr, W. S.] USN, Med Res Ctr, Silver Spring, MD USA. RI Duyn, Jozef/F-2483-2010; Fukunaga, Masaki/F-6441-2013 OI Fukunaga, Masaki/0000-0003-1010-2644 NR 0 TC 0 Z9 0 U1 0 U2 0 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 2009 VL 32 MA 0033 BP A11 EP A11 PG 1 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 438FT UT WOS:000265542000035 ER PT J AU Rogers, VE Lewin, DS Geiger-Brown, J Winnie, G AF Rogers, V. E. Lewin, D. S. Geiger-Brown, J. Winnie, G. TI OBSTRUCTIVE SLEEP APNEA AND SICKLE CELL DISEASE SEVERITY IN CHILDREN SO SLEEP LA English DT Meeting Abstract CT 23rd Annual Meeting of the Associated-Professional-Sleep-Societies CY JUN 06-11, 2009 CL Seattle, WA SP Associated Profess Sleep Soc C1 [Rogers, V. E.; Geiger-Brown, J.] Univ Maryland, Baltimore, MD 21201 USA. [Lewin, D. S.] NHLBI, Div Lung Dis, Bethesda, MD 20892 USA. [Winnie, G.] Childrens Natl Med Ctr, Dept Allergy Pulm & Sleep Med, Washington, DC 20010 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 2009 VL 32 MA 0272 BP A91 EP A91 PG 1 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 438FT UT WOS:000265542000274 ER PT J AU McCall, C Blascovich, J Young, A Persky, S AF McCall, Cade Blascovich, Jim Young, Ariana Persky, Susan TI Proxemic behaviors as predictors of aggression towards Black (but not White) males in an immersive virtual environment SO SOCIAL INFLUENCE LA English DT Article DE Aggression; Implicit attitudes; Proxemics; Prejudice; Nonverbal behavior ID SOCIAL COGNITION; PREJUDICE; QUESTIONNAIRE; TECHNOLOGY; ATTITUDES; DISTANCE; POSTURE; SELF AB This study investigated the relationship between participant proxemic behavior and overt aggression during interactions with Black and White agents in an immersive virtual environment. In a series of two tasks, participants first interacted with two male agents (each of the same race) and then engaged in a violent shooting game with those agents. Participants' proxemic behaviors (interpersonal distance and head movements) during the first task predicted aggressive and hostile participant shots against Black but not White agents in the subsequent task. Results supported the value of proxemic variables in predicting aggression and the utility of IVET for experimental social psychology. C1 [McCall, Cade] Univ Calif Santa Barbara, Dept Psychol, Santa Barbara, CA 93106 USA. [Persky, Susan] NHGRI, Bethesda, MD 20892 USA. RP McCall, C (reprint author), Univ Calif Santa Barbara, Dept Psychol, Santa Barbara, CA 93106 USA. EM mccall@psych.ucsb.edu NR 30 TC 18 Z9 19 U1 3 U2 7 PU PSYCHOLOGY PRESS PI HOVE PA 27 CHURCH RD, HOVE BN3 2FA, EAST SUSSEX, ENGLAND SN 1553-4510 J9 SOC INFLUENCE JI Soc. Influ. PY 2009 VL 4 IS 2 BP 138 EP 154 DI 10.1080/15534510802517418 PG 17 WC Psychology, Social SC Psychology GA 687GQ UT WOS:000284767400004 ER PT J AU Beaton, EA Schmidt, LA Schulkin, J Antony, MM Swinson, RP Hall, GB AF Beaton, Elliott A. Schmidt, Louis A. Schulkin, Jay Antony, Martin M. Swinson, Richard P. Hall, Geoffrey B. TI Different fusiform activity to stranger and personally familiar faces in shy and social adults SO SOCIAL NEUROSCIENCE LA English DT Article ID HUMAN EXTRASTRIATE CORTEX; FACIAL EXPRESSIONS; SELECTIVE ATTENTION; FUNCTIONAL MRI; SHYNESS; PERCEPTION; AUTISM; PHOBIA; AREA; CHILDREN AB Although shyness is associated with deficits in different aspects of face processing including face recognition and facial emotions, we know relatively little about the neural correlates of face processing among individuals who are shy. Here we show reduced activation to stranger faces among shy adults in a key brain area involved in face processing. Event-related functional magnetic resonance imaging scans were acquired on 12 shy and 12 social young adults during the rapid presentation of stranger and personally familiar neutral faces. Shy adults exhibited significantly less bilateral activation in the fusiform face area (FFA) in response to stranger faces and significantly greater bilateral activation in the same region to personally familiar faces than their social counterparts. Shy adults also exhibited significantly greater right amygdala activation in response to stranger faces than social adults. Among social adults, stranger faces elicited greater FFA activation than personally familiar faces. Findings suggest that there are distinct patterns of neural activation in the FFA in response to viewing stranger and personally familiar faces among shy and social adults. C1 [Schmidt, Louis A.] McMaster Univ, Dept Psychol Neurosci & Behav, Hamilton, ON L8S 4K1, Canada. [Schulkin, Jay] NIH, Bethesda, MD 20892 USA. [Schulkin, Jay] Georgetown Univ, Washington, DC USA. [Antony, Martin M.] Ryerson Univ, Toronto, ON, Canada. [Antony, Martin M.; Hall, Geoffrey B.] St Josephs Healthcare, Hamilton, ON, Canada. RP Schmidt, LA (reprint author), McMaster Univ, Dept Psychol Neurosci & Behav, 1280 Main St W, Hamilton, ON L8S 4K1, Canada. EM schmidtl@mcmaster.ca; hallg@mcmaster.ca RI Antony, Martin/K-1991-2012; OI Antony, Martin/0000-0002-3508-377X; Beaton, Elliott/0000-0001-7631-4637 FU Natural Sciences and Engineering Council of Canada (NSERC); Louis Schmidt and a Father Sean O'Sullivan Research Centre (FSORC) Post-doctoral Fellowship FX The first author is now at the M. I. N. D. Institute at the University of California, Davis. This research was funded by a grant from the Natural Sciences and Engineering Council of Canada (NSERC) awarded to Louis Schmidt and a Father Sean O'Sullivan Research Centre (FSORC) Post-doctoral Fellowship awarded to Elliott Beaton. We wish to thank Sue McKee for her assistance with data collection and Jami Sawyer and Jessica Shelley for their help with data entry. NR 39 TC 15 Z9 17 U1 4 U2 11 PU PSYCHOLOGY PRESS PI HOVE PA 27 CHURCH RD, HOVE BN3 2FA, EAST SUSSEX, ENGLAND SN 1747-0919 J9 SOC NEUROSCI JI Soc. Neurosci. PY 2009 VL 4 IS 4 BP 308 EP 316 AR PII 909874996 DI 10.1080/17470910902801021 PG 9 WC Neurosciences; Psychology SC Neurosciences & Neurology; Psychology GA 462QY UT WOS:000267371900003 PM 19322727 ER PT J AU Zamboni, G Gozzi, M Krueger, F Duhamel, JR Sirigu, A Grafman, J AF Zamboni, Giovanna Gozzi, Marta Krueger, Frank Duhamel, Jean-Rene Sirigu, Angela Grafman, Jordan TI Individualism, conservatism, and radicalism as criteria for processing political beliefs: A parametric fMRI study SO SOCIAL NEUROSCIENCE LA English DT Article DE Politics; Multidimensional scaling; Parametric fMRI; Social cognition; Medial prefrontal cortex; Temporoparietal junction; Ventral striatum ID DORSOLATERAL PREFRONTAL CORTEX; COGNITIVE NEUROSCIENCE; WORKING-MEMORY; FRONTAL-CORTEX; NEURAL BASIS; AUTOBIOGRAPHICAL MEMORY; DECISION-MAKING; SOCIAL-BEHAVIOR; HUMAN BRAIN; INSIGHTS AB Politics is a manifestation of the uniquely human ability to debate, decide, and reach consensus on decisions affecting large groups over long durations of time. Recent neuroimaging studies on politics have focused on the association between brain regions and specific political behaviors by adopting party or ideological affiliation as a criterion to classify either experimental stimuli or subjects. However, it is unlikely that complex political beliefs (i.e., othe government should protect freedom of speecho) are evaluated only on a liberal-to-conservative criterion. Here we used multidimensional scaling and parametric functional magnetic resonance imaging to identify which criteria/dimensions people use to structure complex political beliefs and which brain regions are concurrently activated. We found that three independent dimensions explained the variability of a set of statements expressing political beliefs and that each dimension was reflected in a distinctive pattern of neural activation: individualism (medial prefrontal cortex and temporoparietal junction), conservatism (dorsolateral prefrontal cortex), and radicalism (ventral striatum and posterior cingulate). The structures we identified are also known to be important in self-other processing, social decision-making in ambivalent situations, and reward prediction. Our results extend current knowledge on the neural correlates of the structure of political beliefs, a fundamental aspect of the human ability to coalesce into social entities. C1 [Grafman, Jordan] Natl Inst Neurol Disorders & Stroke, Cognit Neurosci Sect, NIH, Bethesda, MD 20892 USA. [Zamboni, Giovanna; Gozzi, Marta] Univ Modena, I-41100 Modena, Italy. [Duhamel, Jean-Rene; Sirigu, Angela] CNRS, Bron, France. RP Grafman, J (reprint author), Natl Inst Neurol Disorders & Stroke, Cognit Neurosci Sect, NIH, Bldg 10,Room 7D43,MSC 1440, Bethesda, MD 20892 USA. EM grafmanj@ninds.nih.gov RI Zamboni, Giovanna/F-3583-2017; OI Zamboni, Giovanna/0000-0002-6133-3373; Grafman, Jordan H./0000-0001-8645-4457 FU National Institute of Neurological Disorders and Stroke Intramural Research Program; Italian Ministry of University and Research FX We thank Davide Prandi for computer programming, Dimitrios Kapogiannis for performing neurological exams, Aron Barbey and Maren Strenziok for valuable suggestions, and Roland Zahn and Kris Knutson for astute imaging analysis advice. This study was supported by the National Institute of Neurological Disorders and Stroke Intramural Research Program (to GZ, MG, FK, and JG) and the Italian Ministry of University and Research (MIUR) (to GZ and MG). GZ is currently at the Nuffield Department of Clinical Medicine, University of Oxford, UK. NR 62 TC 24 Z9 25 U1 7 U2 38 PU PSYCHOLOGY PRESS PI HOVE PA 27 CHURCH RD, HOVE BN3 2FA, EAST SUSSEX, ENGLAND SN 1747-0919 J9 SOC NEUROSCI JI Soc. Neurosci. PY 2009 VL 4 IS 5 BP 367 EP 383 AR PII 912764185 DI 10.1080/17470910902860308 PG 17 WC Neurosciences; Psychology SC Neurosciences & Neurology; Psychology GA 492OP UT WOS:000269668500001 PM 19562629 ER PT J AU Blair, RJR Blair, KS AF Blair, R. J. R. Blair, Karina S. BE Decety, J Ickes, W TI Empathy, Morality, and Social Convention: Evidence from the Study of Psychopathy and Other Psychiatric Disorders SO SOCIAL NEUROSCIENCE OF EMPATHY LA English DT Article; Book Chapter ID PRESCHOOL CHILDRENS CONCEPTIONS; PEDIATRIC BIPOLAR DISORDER; EVENT-RELATED FMRI; RESPONSE-REVERSAL; NEURAL BASIS; AUTISM; FACES; EXPRESSIONS; MECHANISMS; ATTENTION C1 [Blair, R. J. R.; Blair, Karina S.] NIMH, Bethesda, MD 20892 USA. RP Blair, RJR (reprint author), NIMH, Bethesda, MD 20892 USA. NR 66 TC 14 Z9 14 U1 1 U2 6 PU M I T PRESS PI CAMBRIDGE PA FIVE CAMBRIDGE CENTER, CAMBRIDGE, MA 02142 USA BN 978-0-262-01297-3 PY 2009 BP 139 EP 152 PG 14 WC Psychology, Clinical; Psychology, Psychoanalysis SC Psychology GA BPL39 UT WOS:000279132400012 ER PT B AU Shamir, L AF Shamir, Lior BE Giordano, AJ Costa, GE TI SOFT COMPUTING IN ASTRONOMY SO SOFT COMPUTING: NEW RESEARCH LA English DT Article; Book Chapter ID COSMIC-RAY REJECTION; DIGITAL SKY SURVEY; SURVEY TELESCOPE; SINGLE IMAGES; IDENTIFICATION; ALGORITHM; PERSEUS; CAMERAS; SYSTEM; PATROL AB In the past few years, the primary tools that serve observational astronomy have been changing significantly. Thus, manually controlled telescopes are gradually being replaced by autonomous robotic systems, which produce vast pipelines of astronomical data. These include multi-million dollar ventures that are considered the primary projects in modem observational astronomy, such as SDSS (Sloan Digital Sky Survey), PAN-STARRS, LSST (Large Synoptic Survey Telescope), and also semi-autonomous space telescopes such as JWST (James Webb Space Telescope). Many smaller-scale ground and space based robotic telescopes also operate, and substantially contribute to the efforts of searching supernovae, planetary eclipses, comets, and asteroids that might pose a future threat to Earth. However, while very many astronomical data are constantly being generated, human identifications are many times impracticably slow. Therefore, one can reasonably assume that many discoveries of significant scientific value are hidden inside the databases generated by robotic telescopes, but cannot be found due to the complex task of mining these data for discoveries. In order to optimize the scientific return of robotic sky surveys, the data should be analyzed in an automated fashion that can detect single events of scientific interest in data sets of millions of recorded astronomical objects. Automated search for scientific discoveries in astronomical images is a formidable task that requires complex decision making. This complexity is caused by the vague definition of events that can be considered "interesting", as there is no "typical" astronomical discovery. Other contributors to this complexity are inaccuracies of the optics and instruments, ever-changing sky opacity and weather conditions, and the presence of artificial satellites and space junks that reflects sunlight in a fashion that is often unpredicted, yet offer no scientific interest. Since astronomical pipeline can generate very many images per day, where each image consists of thousands of astronomical objects, even a small percentage of false positives can make a proposed solution impractical. The complex environment introduced by the increasing importance of autonomous sky surveys initiated a continuous effort of development and implementation of soft computing-based solutions to astronomical pipeline processing. In this chapter we describe the: challenging problems of automating the analysis of astronomical images, present existing soft computing-based solutions, and discuss future directions of soft computing in observational astronomy. C1 [Shamir, Lior] Michigan Technol Univ, Dept Phys, Houghton, MI 49931 USA. [Shamir, Lior] NIA, NIH, Bethesda, MD 20892 USA. RP Shamir, L (reprint author), Michigan Technol Univ, Dept Phys, Houghton, MI 49931 USA. NR 77 TC 0 Z9 0 U1 1 U2 1 PU NOVA SCIENCE PUBLISHERS, INC PI HAUPPAUGE PA 400 OSER AVE, STE 1600, HAUPPAUGE, NY 11788-3635 USA BN 978-1-60456-883-7 PY 2009 BP 229 EP 262 PG 34 WC Computer Science, Artificial Intelligence; Computer Science, Theory & Methods SC Computer Science GA BMR68 UT WOS:000273414600010 ER PT B AU Soekadar, SR Caria, A Murguialday, AR Birbaumer, N AF Soekadar, Surjo R. Caria, Andrea Murguialday, Ander Ramos Birbaumer, Niels BE Johnsen, N Agerskov, R TI Rehabilitation After Stroke Using Brain-Computer-Interfaces and Neurostimulation SO SOMATOSENSORY CORTEX: ROLES, INTERVENTIONS AND TRAUMAS SE Neurology Laboratory and Clinical Research Series LA English DT Article; Book Chapter DE neurotechnology; brain-computer-interface; neurostimulation; neuro-rehabilitation; stroke ID TRANSCRANIAL MAGNETIC STIMULATION; SLOW CORTICAL POTENTIALS; PRIMARY MOTOR CORTEX; ELECTRICAL-STIMULATION; CONTROLLED-TRIAL; CEREBRAL-CORTEX; SELF-REGULATION; MOVEMENT; COMMUNICATION; SIGNALS AB This chapter deals with the current state and perspective of neurotechnology, particular the use of brain computer interfaces (BCI) and neurostimulation in the rehabilitation of stroke. While 20 years ago brain-computer-interfaces that utilize neurophysiologic or metabolic signals originating in the brain to activate or deactivate external devices or computers have been used by a handful of research groups only, there are now - after the decade of the brain - several hundred groups world-wide working in this field. Additionally, the modulation of brain activity by non-invasive cortical stimulation undergoes a renaissance. New and innovative techniques to modulate or even enhance brain functions have emerged. After a short introduction of the BCI-systems that have been developed and successfully used in patients with intractable epilepsy, attention deficit disorder, ALS and chronic pain since 1979 by the University of Tuebingen group, recent developments in the use of BCI technology and neurostimulation for stroke survivors will be sketched and exemplified by our latest results. Limits and current challenges in the use of BCI technology and brain stimulation will be highlighted and discussed. The chapter closes with an outlook on future developments and prospects introducing promising developments such as the combination of BCI systems with non-invasive forms of neurostimulation and e.g. functional electric stimulation (FES). C1 [Soekadar, Surjo R.] Univ Tubingen, Dept Psychiat & Psychotherapy, Neurostimulat Unit, D-72074 Tubingen, Germany. [Soekadar, Surjo R.] NINDS, NIH, Human Cort Physiol & Stroke Neurorehabil Sect, Bethesda, MD 20892 USA. [Caria, Andrea; Murguialday, Ander Ramos; Birbaumer, Niels] Univ Tubingen, Inst Med Psychol & Behav Neurobiol, D-72074 Tubingen, Germany. RP Soekadar, SR (reprint author), Univ Tubingen, Dept Psychiat & Psychotherapy, Neurostimulat Unit, D-72074 Tubingen, Germany. NR 101 TC 0 Z9 0 U1 0 U2 2 PU NOVA SCIENCE PUBLISHERS, INC PI HAUPPAUGE PA 400 OSER AVE, STE 1600, HAUPPAUGE, NY 11788-3635 USA BN 978-1-60741-876-4 J9 NEUROL LAB CLIN RES PY 2009 BP 101 EP 119 PG 19 WC Clinical Neurology SC Neurosciences & Neurology GA BPD20 UT WOS:000278553000005 ER PT J AU Li, SY Lu, Q Fu, WJ Romero, R Cui, YH AF Li, Shaoyu Lu, Qing Fu, Wenjiang Romero, Roberto Cui, Yuehua TI A Regularized Regression Approach for Dissecting Genetic Conflicts that Increase Disease Risk in Pregnancy SO STATISTICAL APPLICATIONS IN GENETICS AND MOLECULAR BIOLOGY LA English DT Article DE complex disease; genetic conflicts; genomic imprinting; maternal-fetal genotype incompatibility; penalized mixture logistic regression ID FOR-GESTATIONAL-AGE; INTRAUTERINE GROWTH RESTRICTION; PENALIZED LOGISTIC-REGRESSION; FETAL-GROWTH; IMPRINTED GENES; MFG TEST; ASSOCIATION; DEFINITION; EXPRESSION; MORBIDITY AB Human diseases developed during pregnancy could be caused by the direct effects of both maternal and fetal genes, and/or by the indirect effects caused by genetic conflicts. Genetic conflicts exist when the effects of fetal genes are opposed by the effects of maternal genes, or when there is a conflict between the maternal and paternal genes within the fetal genome. The two types of genetic conflicts involve the functions of different genes in different genomes and are genetically distinct. Differentiating and further dissecting the two sets of genetic conflict effects that increase disease risk during pregnancy present statistical challenges, and have been traditionally pursued as two separate endeavors. In this article, we develop a unified framework to model and test the two sets of genetic conflicts via a regularized regression approach. Our model is developed considering real situations in which the paternal information is often completely missing; an assumption that fails most of the current family-based studies. A mixture model-based penalized logistic regression is proposed for data sampled from a natural population. We develop a variable selection procedure to select significant genetic features. Simulation studies show that the model has high power and good false positive control under reasonable sample sizes and disease allele frequency. A case study of small for gestational age (SGA) is provided to show the utility of the proposed approach. Our model provides a powerful tool for dissecting genetic conflicts that increase disease risk during pregnancy, and offers a testable framework for the genetic conflict hypothesis previously proposed. C1 [Li, Shaoyu; Lu, Qing; Fu, Wenjiang; Cui, Yuehua] Michigan State Univ, E Lansing, MI 48824 USA. [Romero, Roberto] NIH, NICHD, Bethesda, MD USA. RP Li, SY (reprint author), Michigan State Univ, E Lansing, MI 48824 USA. EM lishaoyu@stt.msu.edu; qlu@epi.msu.edu; fuw@epi.msu.edu; prbchiefstaff@med.wayne.edu; cui@stt.msu.edu FU NSF [DMS-0707031]; Eunice Kennedy Shriver National Institute of Child Health and Human Developmen; NIH; DHHS FX The authors thank the editor and two anonymous referees for their constructive comments and useful suggestions that greatly improved the manuscript. This work was supported in part by NSF grant DMS-0707031 and by the Intramural Research Program of the Eunice Kennedy Shriver National Institute of Child Health and Human Development, NIH, DHHS. Address for correspondence: Dr. Yuehua Cui, Department of Statistics & Probability, Michigan State University, East Lansing, MI 48824. NR 49 TC 14 Z9 14 U1 0 U2 2 PU WALTER DE GRUYTER GMBH PI BERLIN PA GENTHINER STRASSE 13, D-10785 BERLIN, GERMANY SN 2194-6302 EI 1544-6115 J9 STAT APPL GENET MOL JI Stat. Appl. Genet. Mol. Biol. PY 2009 VL 8 IS 1 AR 45 DI 10.2202/1544-6115.1474 PG 30 WC Biochemistry & Molecular Biology; Mathematical & Computational Biology; Statistics & Probability SC Biochemistry & Molecular Biology; Mathematical & Computational Biology; Mathematics GA 513IP UT WOS:000271316200002 ER PT J AU Yuan, M Tian, X Zheng, G Yang, YN AF Yuan, Min Tian, Xin Zheng, Gang Yang, Yaning TI Adaptive Transmission Disequilibrium Test for Family Trio Design SO STATISTICAL APPLICATIONS IN GENETICS AND MOLECULAR BIOLOGY LA English DT Article DE adaptive TDT; conditional power; efficiency robustness; genetic model selection; Hardy-Weinberg disequilibrium; MAX-type tests; TDT-type tests; FBAT; constrained likelihood ratio test ID CANDIDATE-GENE ASSOCIATION; HARDY-WEINBERG DISEQUILIBRIUM; GENOTYPE RELATIVE-RISKS; ROBUST LINKAGE TESTS; UNIFIED APPROACH; AFFECTED SIBS; PARENTS; POWER; LOCI; IDDM AB The transmission disequilibrium test (TDT) is a standard method to detect association using family trio design. It is optimal for an additive genetic model. Other TDT-type tests optimal for recessive and dominant models have also been developed. Association tests using family data, including the TDT-type statistics, have been unified to a class of more comprehensive and flexable family-based association tests (FBAT). TDT-type tests have high efficiency when the genetic model is known or correctly specified, but may lose power if the model is mis-specified. Hence tests that are robust to genetic model mis-specification yet efficient are preferred. Constrained likelihood ratio test (CLRT) and MAX-type test have been shown to be efficiency robust. In this paper we propose a new efficiency robust procedure, referred to as adaptive TDT (aTDT). It uses the Hardy-Weinberg disequilibrium coefficient to identify the potential genetic model underlying the data and then applies the TDT-type test (or FBAT for general applications) corresponding to the selected model. Simulation demonstrates that aTDT is efficiency robust to model mis-specifications and generally outperforms the MAX test and CLRT in terms of power. We also show that aTDT has power close to, but much more robust, than the optimal TDT-type test based on a single genetic model. Applications to real and simulated data from Genetic Analysis Workshop (GAW) illustrate the use of our adaptive TDT. C1 [Yuan, Min; Yang, Yaning] Univ Sci & Technol China, Hefei, Peoples R China. [Tian, Xin; Zheng, Gang] NHLBI, Bethesda, MD 20892 USA. RP Yuan, M (reprint author), Univ Sci & Technol China, Hefei, Peoples R China. EM myuan@mail.ustc.edu.cn; tianx@nhlbi.nih.gov; zhengg@nhlbi.nih.gov; ynyang@gmail.com FU China NSF FX Yang was partially supported by China NSF grant. NR 40 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 2009 VL 8 IS 1 AR 30 DI 10.2202/1544-6115.1451 PG 22 WC Biochemistry & Molecular Biology; Mathematical & Computational Biology; Statistics & Probability SC Biochemistry & Molecular Biology; Mathematical & Computational Biology; Mathematics GA 465QI UT WOS:000267601500004 ER PT J AU Vexler, A Wu, CQ Liu, AY Whitcomb, BW Schisterman, EF AF Vexler, Albert Wu, Chengqing Liu, Aiyi Whitcomb, Brian W. Schisterman, Enrique F. TI An extension of a change-point problem SO STATISTICS LA English DT Article DE Doob decomposition; change-point; classification; CUSUM statistics; likelihood ratio; limit of detection; martingale; martingale transforms; Shiryayev-Roberts statistics ID SEQUENTIAL-ANALYSIS; LINEAR-REGRESSION; DETECTION LIMITS; FALSE ALARM; RUN-LENGTH; SURVEILLANCE; EXPOSURE; ALTERNATIVES; TESTS; MODEL AB We consider a specific classification problem in the context of change-point detection. We present generalized classical maximum likelihood tests for homogeneity of the observed sample in a simple form which avoids the complex direct estimation of unknown parameters. This paper proposes a martingale approach to transformation of test statistics. For sequential and retrospective testing problems, we propose the adapted Shiryayev-Roberts statistics in order to obtain simple tests with asymptotic power one. An important application of the developed methods is in the analysis of exposure's measurements subject to limits of detection in occupational medicine. C1 [Vexler, Albert] SUNY Buffalo, Dept Biostat, Buffalo, NY 14260 USA. [Wu, Chengqing; Liu, Aiyi; Whitcomb, Brian W.; Schisterman, Enrique F.] NICHD, Div Epidemiol Stat & Prevent Res, NIH, Bethesda, MD USA. RP Vexler, A (reprint author), SUNY Buffalo, Dept Biostat, Buffalo, NY 14260 USA. EM avexler@buffalo.edu OI Liu, Aiyi/0000-0002-6618-5082; Schisterman, Enrique/0000-0003-3757-641X NR 33 TC 2 Z9 2 U1 0 U2 1 PU TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXON, ENGLAND SN 0233-1888 J9 STATISTICS JI Statistics PY 2009 VL 43 IS 3 BP 213 EP 225 AR PII 907042540 DI 10.1080/02331880802395930 PG 13 WC Statistics & Probability SC Mathematics GA 448ED UT WOS:000266245000001 ER PT J AU Zheng, G Balakrishnan, N Park, S AF Zheng, Gang Balakrishnan, N. Park, Sangun TI Fisher information in ordered data: A review SO STATISTICS AND ITS INTERFACE LA English DT Article DE Asymptotics; censored data; characterizations; hazard functions; life testing; order statistics; ranked set sampling ID II CENSORED-DATA; QUANTITATIVE-TRAIT LOCI; RANKED SET SAMPLES; EXPONENTIATED EXPONENTIAL FAMILY; EXACT LIKELIHOOD INFERENCE; TUKEYS LINEAR SENSITIVITY; DISCORDANT SIB PAIRS; RECORD VALUES; WEIBULL-DISTRIBUTION; CORRELATION-COEFFICIENT AB Fisher information is a fundamental concept of statistical inference and plays an important role in many areas of statistical analysis. Research in Fisher information in order statistics started around 1965 by John Tukey. Recently, the research in this area has been extended from classical order statistics and Type-I and Type-II censored data to other situations, including hybrid censoring, random censoring, progressive censoring, record values, and concomitants, with new applications in genetic linkage analysis. In this article, we provide a comprehensive review of various developments concerning the theory and applications of Fisher information in ordered data, show how Fisher information provides insight into properties of many statistical procedures involving order statistics. C1 [Zheng, Gang] NHLBI, Off Biostat Res, Bethesda, MD 20892 USA. [Balakrishnan, N.] McMaster Univ, Dept Math & Stat, Hamilton, ON L8S 4K1, Canada. [Park, Sangun] Yonsei Univ, Dept Appl Stat, Seoul 120749, South Korea. RP Zheng, G (reprint author), NHLBI, Off Biostat Res, 6701 Rockledge Dr, Bethesda, MD 20892 USA. EM zhengg@nhlbi.nih.gov; bala@univmail.cis.mcmaster.ca; sangun@yonsei.ac.kr FU Yonsei University FX Partially supported by Yonsei University Research Fund of 2007. NR 106 TC 6 Z9 6 U1 2 U2 5 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 2009 VL 2 IS 1 BP 101 EP 113 PG 13 WC Mathematical & Computational Biology; Mathematics, Interdisciplinary Applications SC Mathematical & Computational Biology; Mathematics GA 660MY UT WOS:000282648900010 ER PT J AU Gail, MH AF Gail, Mitchell H. TI Applying the Lorenz curve to disease risk to optimize health benefits under cost constraints SO STATISTICS AND ITS INTERFACE LA English DT Article DE Absolute risk; cost constraints; constrained optimization; cumulative incidence; disease prevention; Lorenz curve; risk prediction model ID OF-FIT TEST; BREAST-CANCER; GINI-INDEX; MODELS AB This paper shows how the Lorenz curve can be used, together with models of disease risk, to allocate scarce resources so as to optimize a health benefit. Consider the example of breast cancer mortality. If there were sufficient resources to provide all women with mammograms, a certain maximal number of lives could be saved. Suppose, however, that only a fraction of that amount of money is available for prevention activities. Suppose that a questionnaire could be given to assess a woman's risk of dying of breast cancer. Depending on the amount of money available, on the ratio of the cost of a questionnaire to the cost of a mammogram, and on the Lorenz curve of the distribution of risks of breast cancer mortality, I calculate the proportion of women who should be given questionnaires, the proportion of women given the questionnaires who should be given mammograms because they have high risks, and the proportion of women not given questionnaires who should be assigned to receive mammograms at random so as to maximize the number of lives saved. C1 NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. RP Gail, MH (reprint author), NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. EM gailm@exchange.nih.gov FU National Cancer Institute FX This work was supported by the Intramural Research Program of the National Cancer Institute. NR 9 TC 8 Z9 8 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 2009 VL 2 IS 2 BP 117 EP 121 PG 5 WC Mathematical & Computational Biology; Mathematics, Interdisciplinary Applications SC Mathematical & Computational Biology; Mathematics GA 660NG UT WOS:000282649700002 PM 19779595 ER PT J AU Chatterjee, N Graubard, BI Gastwirth, JL AF Chatterjee, Nilanjan Graubard, Barry I. Gastwirth, Joseph L. TI The use of the risk percentile curve in the analysis of epidemiologic data SO STATISTICS AND ITS INTERFACE LA English DT Article DE Relative risk; Absolute risk; Population attributable risk; Logistic regression; Cox proportional hazard regression; Case-control study; Cohort study; Attributable risk reduction curve; Expectancy curve; Survey data ID ADJUSTMENT; CANCER AB Economists and social scientists have used percentile-based curves, e.g., the Lorenz curve, to summarize data from positive random variables, especially skewed data such as income. Measures of interest, e.g., the Gini index of relative inequality, correspond to areas defined by the curves. In this paper we explore the usefulness of risk-percentile and related curves in epidemiology, especially when the exposure data is skewed. These curves are defined and risk measures, e.g. the population attributable risk are related to areas under them for data from either a cohort or a case-control study. Regression spline methods of estimating these curves are used as they do not require a pre-specified risk model. The concepts are illustrated by analyzing data from a cohort study of dietary red meat consumption and all-cause mortality and a case-control study of serum homocysteine level and colorectal cancer. These examples show that the risk percentile curves often are more useful than presenting the risk as a function of the raw exposure data as the later graph is often dominated by the tails when the data is skewed. Furthermore, the risk percentile curve is more informative than the commonly used method of presenting the average risk in categories defined by several fixed percentiles such as quartiles or quintiles. Indeed, the risk averages for these categories can be obtained from the risk-percentile curve. C1 [Chatterjee, Nilanjan; Graubard, Barry I.] NCI, Biostat Branch, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. [Gastwirth, Joseph L.] George Washington Univ, Dept Stat, Washington, DC 20052 USA. RP Chatterjee, N (reprint author), NCI, Biostat Branch, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. EM graubarb@mail.nih.gov NR 20 TC 0 Z9 0 U1 0 U2 2 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 2009 VL 2 IS 2 BP 123 EP 131 PG 9 WC Mathematical & Computational Biology; Mathematics, Interdisciplinary Applications SC Mathematical & Computational Biology; Mathematics GA 660NG UT WOS:000282649700003 ER PT J AU Buckman, DW Li, ZH AF Buckman, Dennis W. Li, Zhaohai TI Missing data methods for linkage analysis of IBS and incomplete IBD from affected sib-pairs SO STATISTICS AND ITS INTERFACE LA English DT Article DE Incomplete data; Missing at random; Identity-by-descent; Identity-by-state; Complex traits; Required sample size; Power; Type I error ID QUANTITATIVE-TRAIT LOCI; GENETICALLY COMPLEX TRAITS; AFFECTED RELATIVE PAIRS; EXTREME DISCORDANT; STRATEGIES; IDENTITY; HUMANS; INFERENCE; MODELS; POWER AB We derive linkage statistics for situations where the number of marker alleles shared identical-by-descent (IBD) is incomplete, and the number of marker alleles shared identical-by-state (IBS) is known. The linkage statistics are based on the assumption that the parental genotypes are missing at random (MAR). We first assume the marker IBD is unambiguous for a sib-pair if the parental genotypes are available. Then we relax this assumption to assess the impact of marker ambiguity. The derivation of each statistic involves a Taylor series expansion of a log likelihood that is a function of the recombination fraction and nuisance parameters and incorporates the missing data situation. The first derivative of the log likelihood is zero under the null hypothesis of no recombination, so the Taylor series expansion of the log likelihood reveals a linkage statistic that is proportional to the second derivative of the log likelihood evaluated at the null hypothesis value of the recombination fraction. We prove that the standardized linkage statistics have asymptotic normal distributions, and we provide required sample sizes and simulation results and consider the impact of parent availability and marker ambiguity. C1 [Buckman, Dennis W.] Informat Management Serv Inc, Silver Spring, MD 20904 USA. [Buckman, Dennis W.; Li, Zhaohai] George Washington Univ, Dept Stat, Washington, DC 20052 USA. [Li, Zhaohai] NCI, Biostat Branch, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. RP Buckman, DW (reprint author), Informat Management Serv Inc, 2501 Prosper Dr,Suite 200, Silver Spring, MD 20904 USA. EM buckmand@imsweb.com; zli@gwu.edu FU NIH [EY014478] FX The work of the second author was supported in part by NIH grant EY014478. NR 32 TC 0 Z9 0 U1 0 U2 1 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 2009 VL 2 IS 2 BP 133 EP 144 PG 12 WC Mathematical & Computational Biology; Mathematics, Interdisciplinary Applications SC Mathematical & Computational Biology; Mathematics GA 660NG UT WOS:000282649700004 ER PT J AU Zheng, G Joo, J Tian, X Wu, CO Lin, JP Stylianou, M Waclawiw, MA Geller, NL AF Zheng, Gang Joo, Jungnam Tian, Xin Wu, Colin O. Lin, Jing-Ping Stylianou, Mario Waclawiw, Myron A. Geller, Nancy L. TI Robust genome-wide scans with genetic model selection using case-control design SO STATISTICS AND ITS INTERFACE LA English DT Article DE Case-control design; Efficiency robustness; Genetic model selection; Genome-wide studies; MAX ID CASE-CONTROL ASSOCIATION; TREND TESTS; SAMPLE-SIZE; DISEQUILIBRIUM; EFFICIENT; SURVIVAL; DISEASES; POWER; LOCI AB In a genome-wide association study with more than 100, 000 (100K) to 1 million single nucleotide polymorphisms (SNPs), the first step is usually a genome-wide scan to identify candidate chromosome regions for further analyses. The goal of the genome-wide scan is to rank all the SNPs based on their association tests or p-values and select the top SNPs. A good ranking procedure ranks the SNPs with true associations as near to the top as possible. This enhances the probability of selecting at least one SNP with a true association. However, if the disease-associated SNPs have moderate genetic effects, the probability that a large number of null SNPs will have extremely small p-values (or large test statistics) is high when screening more than 300K SNPs. Therefore, when selecting a small fraction of top SNPs (usually less than 5%), the probability of selecting at least one SNP with a true association is usually less than 80% unless the sample size is large. Robust statistics have been proposed to rank all the SNPs (e.g., MAX3 and MIN2). In this article we consider genome-wide scans with a genetic model selection and compare this proposed method to the existing approaches. Results from simulation studies are presented. C1 [Zheng, Gang; Joo, Jungnam; Tian, Xin; Wu, Colin O.; Lin, Jing-Ping; Stylianou, Mario; Waclawiw, Myron A.; Geller, Nancy L.] NHLBI, Off Biostat Res, Bethesda, MD 20892 USA. RP Zheng, G (reprint author), NHLBI, Off Biostat Res, 6701 Rockledge Dr, Bethesda, MD 20892 USA. EM zhengg@nhlbi.nih.gov; jooj@nhlbi.nih.gov; tianx@nhlbi.nih.gov; wuc@nhlbi.nih.gov; linj@nhlbi.nih.gov; stylianm@nhlbi.nih.gov; waclawim@nhlbi.nih.gov; gellern@nhlbi.nih.gov NR 30 TC 5 Z9 5 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 2009 VL 2 IS 2 BP 145 EP 151 PG 7 WC Mathematical & Computational Biology; Mathematics, Interdisciplinary Applications SC Mathematical & Computational Biology; Mathematics GA 660NG UT WOS:000282649700005 ER PT J AU Li, QZ Liu, AY Yu, K Yu, KF AF Li, Qizhai Liu, Aiyi Yu, Kai Yu, Kai F. TI A weighted rank-sum procedure for comparing samples with multiple endpoints SO STATISTICS AND ITS INTERFACE LA English DT Article DE Asymptotic normality; Behrens-Fisher problem; Case-Control; Clinical trials; Multiple endpoints; Rank-sum statistics; Weights ID BEHRENS-FISHER PROBLEM; TRIALS; TESTS AB For comparing the distribution of two samples with multiple endpoints, O'Brien (1984) proposed rank-sum-type test statistics. Huang et al. (2005) extended these statistics to the general nonparametric Behrens-Fisher hypothesis problem and obtained improved test statistics by replacing the ad hoc variance with the asymptotic variance of the rank-sum statistics. In this paper we generalize the work of O'Brien (1984) and Huang et al. (2005) and propose a weighted rank-sum statistic. We show that the weighted rank-sum statistic is asymptotically normally distributed, permitting the computation of power, p-values and confidence intervals. We further demonstrate via simulation that the weighted rank-sum statistic is efficient in controlling the type I error rate and under certain alternatives, is more powerful than the statistics of O'Brien (1984) and Huang et al. (2005). C1 [Li, Qizhai; Yu, Kai] NCI, Biostat Branch, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. [Li, Qizhai] Chinese Acad Sci, Acad Math & Syst Sci, Beijing 100864, Peoples R China. EM liqz@amss.ac.cn; liua@mail.nih.gov; yuka@mail.nih.gov; yukf@mail.nih.gov FU National Institutes of Health; Chinese Academy of Sciences FX This research has been supported by the Intramural Research Program of the National Institutes of Health and the Knowledge Innovation Program of the Chinese Academy of Sciences. NR 9 TC 1 Z9 1 U1 0 U2 4 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 2009 VL 2 IS 2 BP 197 EP 201 PG 5 WC Mathematical & Computational Biology; Mathematics, Interdisciplinary Applications SC Mathematical & Computational Biology; Mathematics GA 660NG UT WOS:000282649700010 PM 19823699 ER PT J AU Kovacic, JC Boehm, M AF Kovacic, Jason C. Boehm, Manfred TI Resident vascular progenitor cells: An emerging role for non-terminally differentiated vessel-resident cells in vascular biology SO STEM CELL RESEARCH LA English DT Review ID HEMATOPOIETIC STEM-CELLS; EPITHELIAL-MESENCHYMAL TRANSITION; MUSCLE-LIKE CELLS; EMBRYONIC ENDOTHELIAL-CELLS; APOE-DEFICIENT MICE; IN-VITRO; SMOOTH-MUSCLE; YOLK-SAC; MOUSE EMBRYO; DORSAL AORTA AB Throughout development and adult life the vasculature exhibits a remarkably dynamic capacity for growth and repair. The vasculature also plays a pivotal role in the execution of other diverse biologic processes, such as the provisioning of early hematopoietic stem cells during embryonic development or the regulation of vascular tone and blood pressure. Adding to this importance, from an anatomical perspective, the vasculature is clearly an omnipresent organ, with few areas of the body that it does not penetrate. Given these impressive characteristics, it is perhaps to be expected that the vasculature should require, or at least be associated with, a ready supply of stem and progenitor cells. However, somewhat surprisingly, it is only now just beginning to be broadly appreciated that the vasculature plays host to a range of vessel-resident stem and progenitor cells. The possibility that these vessel-resident cells are implicated in processes as diverse as tumor vascularization and adaptive vascular remodeling appears likely, and several exciting avenues for clinical translation are already under investigation. This review explores the various stem and progenitor cell populations that are resident in the microvasculature, endothelium, and vessel watts and vessel-resident cells capable of phenotypic transformation. Published by Elsevier B.V. C1 [Kovacic, Jason C.; Boehm, Manfred] NHLBI, Translat Med Branch, Div Intramural Res, NIH, Bethesda, MD 20892 USA. RP Boehm, M (reprint author), NHLBI, Translat Med Branch, Div Intramural Res, NIH, Bldg 10, Bethesda, MD 20892 USA. EM boehmm2@mail.nih.gov FU NHLBI; NIH FX We acknowledge the professional skills and advice of Dr. Christian A. Combs and Dr. Daniela Matide (Light Microscopy Core Facility, National Heart, Lung, and Blood Institute, National Institutes of Health) for their assistance with Fig. 1. J.K. and M.B. are funded by the intramural research program of the NHLBI, NIH. NR 118 TC 39 Z9 39 U1 0 U2 4 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 1873-5061 J9 STEM CELL RES JI Stem Cell Res. PD JAN PY 2009 VL 2 IS 1 BP 2 EP 15 DI 10.1016/j.scr.2008.05.005 PG 14 WC Cell & Tissue Engineering; Biotechnology & Applied Microbiology; Cell Biology SC Cell Biology; Biotechnology & Applied Microbiology GA 495QL UT WOS:000269909000002 PM 19383404 ER PT J AU Kuznetsov, SA Mankani, MH Bianco, P Robey, PG AF Kuznetsov, Sergei A. Mankani, Mahesh H. Bianco, Paolo Robey, Pamela G. TI Enumeration of the colony-forming units-fibroblast from mouse and human bone marrow in normal and pathological conditions SO STEM CELL RESEARCH LA English DT Review ID MESENCHYMAL STEM-CELLS; FETAL CALF SERUM; FORMATION IN-VITRO; STROMAL CELLS; CFU-F; PROGENITOR CELLS; PRECURSOR-CELLS; MYELOPROLIFERATIVE DISORDERS; PROLIFERATIVE CAPACITY; OSTEOPROGENITOR CELLS AB Bone marrow stromal cell populations, containing a subset of multipotential skeletal stem cells, are increasingly contemplated for use in tissue engineering and stem cell therapy, whereas their involvement in the pathogenetic mechanisms of skeletal disorders is far less recognized. We compared the concentrations of stromal clonogenic cells, colony forming units-fibroblast (CFU-Fs), in norm and pathology. Initially, culture conditions were optimized by demonstrating that fetal bovine serum heat inactivation could significantly repress colony formation. Using non-heat-inactivated fetal bovine serum, the concentration of CFU-Fs; (colony-forming efficiency, CFE) ranged from 3.5 +/- 1.0 to 11.5 +/- 4.0 per 1 X 10(5) nucleated cells in five inbred mouse strains. In four transgenic lines with profound bone involvement, CFE was either significantly reduced or increased compared to wild-type littermates. In normal human donors, CFE decreased slightly with age and averaged 52.2 +/- 4.1 for children and 32.3 +/- 3.0 for adults. CFE was significantly altered in patients with several skeletal, metabolic, and hematological disorders: reduced in congenital generalized lipodystrophy, achondroplasia (SADDAN), pseudoachondroplasia, and Paget disease of bone and elevated in alcaptonuria and sickle cell anemia. Our findings indicate that under appropriate culture conditions, CFE values may provide useful insights into bone/bone marrow pathophysiology. (C) 2008 Elsevier B.V. All rights reserved. C1 [Kuznetsov, Sergei A.; Mankani, Mahesh H.; Robey, Pamela G.] Natl Inst Dent & Craniofacial Res, Craniofacial & Skeletal Dis Branch, NIH, US Dept HHS, Bethesda, MD 20892 USA. [Bianco, Paolo] Univ Roma La Sapienza, Dipartimento Med Sperimentale & Patol, I-00161 Rome, Italy. RP Kuznetsov, SA (reprint author), Natl Inst Dent & Craniofacial Res, Craniofacial & Skeletal Dis Branch, NIH, US Dept HHS, 30 Convent Dr MSC 4370, Bethesda, MD 20892 USA. EM skuznets@mail.nih.gov RI Robey, Pamela/H-1429-2011 OI Robey, Pamela/0000-0002-5316-5576 FU National Institute of Dental and Craniofacial Research; IRP; NIH; DHHS FX The authors are grateful to Drs. Michael Collins (NIDCR, NIH); Jose Luis Franco and Steven M. Holland (NIAID, NIH); Glen Nuckolls (NIAMS, NIH); Clair A. Francomano (NIA, NIH); Elif Arioglu Oral and Philip Gorden (NIDDK, NIH); William Gahl (NHGRI, NIH); Arabella Leet, Paul Sponsetter, Neat Fedarko, and lain McIntosh (Johns Hopkins University, Baltimore, MD); John W.T. Walker and Stephen L.-K. Yen (Children's Hospital, Los Angeles, CA); Fred Singer (John Wayne Cancer Institute, Santa Monica, CA); Alan Aaron and Brian Evans (Georgetown University, Washington, DC); Paul A. Manner (George Washington University, Washington, DC); and Michael Keating (Children's National Medicine Center, Washington, DC) for providing human bone and bone marrow. We are indebted to Drs. Kenn Holmbeck (NIDCR, NIH); Tomoko Iwata and Clair A. Francomano (NIA, NIH); Cui-Ling Li and Chu-Xia Deng (NIDDK, NIH); Lorraine A. Fitzpatrick (GtaxoSmithKline, Collegeville, PA); and Laura Calvi, Henry M. Kronenberg, and Ernestina Schipani (Massachusetts General Hospital and Harvard Medical School, Boston, MA) for providing transgenic mice with skeletal phenotypes. This research was supported by the Division of Intramural Research of the National Institute of Dental and Craniofacial Research, IRP, NIH, DHHS. NR 107 TC 36 Z9 38 U1 2 U2 3 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 1873-5061 J9 STEM CELL RES JI Stem Cell Res. PD JAN PY 2009 VL 2 IS 1 BP 83 EP 94 DI 10.1016/j.scr.2008.07.007 PG 12 WC Cell & Tissue Engineering; Biotechnology & Applied Microbiology; Cell Biology SC Cell Biology; Biotechnology & Applied Microbiology GA 495QL UT WOS:000269909000010 PM 19383412 ER PT J AU Pistollato, F Chen, HL Rood, BR Zhang, HZ D'Avella, D Denaro, L Gardiman, M Kronnie, GT Schwartz, PH Favaro, E Indraccolo, S Basso, G Panchision, DM AF Pistollato, Francesca Chen, Hui-Ling Rood, Brian R. Zhang, Hui-Zhen D'Avella, Domenico Denaro, Luca Gardiman, Marina Kronnie, Geertruy Te Schwartz, Philip H. Favaro, Elena Indraccolo, Stefano Basso, Giuseppe Panchision, David M. TI Hypoxia and HIF1 alpha Repress the Differentiative Effects of BMPs in High-Grade Glioma SO STEM CELLS LA English DT Article DE Brain tumor; High-grade glioma; Oxygen; Bone morphogenetic proteins; Smad; Hypoxia inducible factor 1 alpha ID BONE MORPHOGENETIC PROTEINS; TUMOR-INITIATING CELLS; GROWTH-FACTOR RECEPTOR; NEURAL STEM-CELLS; INDUCIBLE FACTOR-1-ALPHA; OXYGEN-TENSION; PROGENITOR CELLS; GENE-EXPRESSION; RADIAL GLIA; MOUSE-BRAIN AB Hypoxia commonly occurs in solid tumors of the central nervous system (CNS) and often interferes with therapies designed to stop their growth. We found that pediatric high-grade glioma (HGG)-derived precursors showed greater expansion under lower oxygen tension, typical of solid tumors, than normal CNS precursors. Hypoxia inhibited p53 activation and subsequent astroglial differentiation of HGG precursors. Surprisingly, although HGG precursors generated endogenous bone morphogenetic protein (BMP) signaling that promoted mitotic arrest under high oxygen tension, this signaling was actively repressed by hypoxia. An acute increase in oxygen tension led to Smad activation within 30 minutes, even in the absence of exogenous BMP treatment. Treatment with BMPs further promoted astroglial differentiation or death of HGG precursors under high oxygen tension, but this effect was inhibited under hypoxic conditions. Silencing of hypoxia-inducible factor 1 alpha (HIF1 alpha) led to Smad activation even under hypoxic conditions, indicating that HIF1 alpha is required for BMP repression. Conversely, BMP activation at high oxygen tension led to reciprocal degradation of HIF1 alpha; this BMP-induced degradation was inhibited in low oxygen. These results show a novel, mutually antagonistic interaction of hypoxia-response and neural differentiation signals in HGG proliferation, and suggest differences between normal and HGG precursors that may be exploited for pediatric brain cancer therapy. STEM CELLS 2009; 27: 7-17 C1 [Pistollato, Francesca; Kronnie, Geertruy Te; Basso, Giuseppe] Univ Padua, Dept Pediat, Hematooncol Lab, Padua, Italy. [D'Avella, Domenico; Denaro, Luca] Univ Padua, Dept Neurosurg, Padua, Italy. [Gardiman, Marina] Univ Padua, Dept Pathol, I-35100 Padua, Italy. [Favaro, Elena] Univ Padua, Dept Oncol & Surg Sci, I-35100 Padua, Italy. [Pistollato, Francesca; Chen, Hui-Ling; Rood, Brian R.; Zhang, Hui-Zhen; Panchision, David M.] Childrens Natl Med Ctr, Childrens Res Inst, Neurosci Res Ctr, Washington, DC 20010 USA. [Schwartz, Philip H.] Childrens Hosp Orange Cty, Res Inst, Orange, CA 92668 USA. [Schwartz, Philip H.] Univ Calif Irvine, Irvine, CA USA. [Indraccolo, Stefano] IRCCS, Ist Oncol Veneto, Padua, Italy. RP Panchision, DM (reprint author), NIMH, Dev Neurobiol Program, NIH, 6001 Execut Blvd,MSC 9641, Bethesda, MD 20892 USA. EM panchisiond@mail.nih.gov RI Indraccolo, Stefano/E-9541-2012; Waha, Andreas/J-2950-2014; Favaro, Elena/Q-4566-2016; OI Indraccolo, Stefano/0000-0002-4810-7136; Favaro, Elena/0000-0001-5376-5515; BASSO, GIUSEPPE/0000-0002-2634-9302 FU Frank and Nancy Parsons Fund; Zickler Fund; Georgia Derrico and Rod Porter Fund; Italian Association AIRC regional grant; FIRB grant; Italian Association for the Fight against Neuroblastoma (Pensiero Project); Italian Ministry of Health Oncology Program 2006; CNMC Research Advisory Council; CHOC Foundation; CNMC Board of Visitors FX This study was supported by funds from the Frank and Nancy Parsons Fund, the Zickler Fund, the Georgia Derrico and Rod Porter Fund for the CNMC/University of Padova Sister Program, the Italian Association AIRC regional grant, the FIRB grant, the Italian Association for the Fight against Neuroblastoma (Pensiero Project), the Italian Ministry of Health Oncology Program 2006, the CNMC Research Advisory Council, the CHOC Foundation for Children, and grants from the CNMC Board of Visitors. We thank Dr Elisabeth Rushing, Armed Forces Institute of Pathology, Washington, DC, and Prof. Felice Giangaspero, Neurosurgery Department, Umberto I Hospital, Rome, Italy, for providing the external secondary neuropathological review. NR 60 TC 36 Z9 36 U1 0 U2 5 PU ALPHAMED PRESS PI DURHAM PA 318 BLACKWELL ST, STE 260, DURHAM, NC 27701-2884 USA SN 1066-5099 J9 STEM CELLS JI Stem Cells PY 2009 VL 27 IS 1 BP 7 EP 17 DI 10.1634/stemcells.2008-0402 PG 11 WC Cell & Tissue Engineering; Biotechnology & Applied Microbiology; Oncology; Cell Biology; Hematology SC Cell Biology; Biotechnology & Applied Microbiology; Oncology; Hematology GA 402SC UT WOS:000263032400003 PM 18832593 ER PT J AU Rao, RC Boyd, J Padmanabhan, R Chenoweth, JG McKay, RD AF Rao, Rajesh C. Boyd, Justin Padmanabhan, Raji Chenoweth, Josh G. McKay, Ronald D. TI Efficient Serum-Free Derivation of Oligodendrocyte Precursors from Neural Stem Cell-Enriched Cultures SO STEM CELLS LA English DT Article DE Oligodendrocytes; Multipotent stem cells; Platelet-derived growth factor; Glycolysis; Extracellular signal-regulated mitogen-activated protein kinases Phosphatidylinositol 3-kinase ID CENTRAL-NERVOUS-SYSTEM; GLIAL PROGENITOR-CELL; RAT-BRAIN OLIGODENDROCYTES; GROWTH-FACTOR RECEPTOR; SIMIAN SARCOMA-VIRUS; IN-VIVO; GENE-EXPRESSION; ALPHA-RECEPTOR; WHITE-MATTER; PDGF AB Oligodendrocytes derived in the laboratory from stem cells have been proposed as a treatment for acute and chronic injury to the central nervous system. Platelet-derived growth factor (PDGF) receptor alpha (PDGFR alpha) signaling is known to regulate oligodendrocyte precursor cell numbers both during development and adulthood. Here, we analyze the effects of PDGFR alpha signaling on central nervous system (CNS) stem cell-enriched cultures. We find that AC133 selection for CNS progenitors acutely isolated from the fetal cortex enriches for PDGF-AA-responsive cells. PDGF-AA treatment of fibroblast growth factor 2-expanded CNS stem cell-enriched cultures increases nestin(+) cell number, viability, proliferation, and glycolytic rate. We show that a brief exposure to PDGF-AA rapidly and efficiently permits the derivation of O4(+) oligodendrocyte-lineage cells from CNS stem cell-enriched cultures. The derivation of oligodendrocyte-lineage cells demonstrated here may support the effective use of stem cells in understanding fate choice mechanisms and the development of new therapies targeting this cell type. STEM CELLS 2009; 27: 116-125 C1 [Rao, Rajesh C.; Boyd, Justin; Padmanabhan, Raji; Chenoweth, Josh G.; McKay, Ronald D.] Natl Inst Neurol Disorders & Stroke, Mol Biol Lab, NIH, Bethesda, MD USA. [Rao, Rajesh C.] Howard Hughes Med Inst, NIH, Res Scholars Program, Bethesda, MD 20817 USA. [Rao, Rajesh C.] Yale Univ, Sch Med, New Haven, CT 06510 USA. RP McKay, RD (reprint author), 35 Convent Dr,MSC 4092, Bethesda, MD 20892 USA. EM mckay@codon.nih.gov OI Rao, Rajesh/0000-0002-5776-8366 FU NIH-National Institute of Neurological Disorders and Stroke; Howard Hughes Medical Institute-NIH Research Scholars Program; NIH Research Award [T35 HL07649] FX The authors thank Jeanette Beers and Ramesh Potla for assistance with fluorescence-activated cell sorter analysis and glycolytic rate assays. We acknowledge Sachiko Murase for critical discussion of the manuscript. We also thank Andreas Theotokis-Androutsellis, Andrei Kuzmichev, Dan Hoeppner, Rea Ravin, and Steven Poser for their advice and suggestions to optimize cell culture and other assays. We are grateful to Hirohide Takebayashi (National Institute for Physiological Sciences, Okazaki, Japan) for his gift of Olig2 antibody. This work was supported by the Intramural Program of the NIH-National Institute of Neurological Disorders and Stroke. R. C. R. was supported by the Howard Hughes Medical Institute-NIH Research Scholars Program and by a T35 HL07649 NIH Research Award through Yale University School of Medicine. R. C. R is currently affiliated with the Department of Ophthalmology, Massachusetts Eye & Ear Infirmary, Harvard Medical School, Boston, MA. NR 81 TC 11 Z9 11 U1 0 U2 1 PU ALPHAMED PRESS PI DURHAM PA 318 BLACKWELL ST, STE 260, DURHAM, NC 27701-2884 USA SN 1066-5099 J9 STEM CELLS JI Stem Cells PY 2009 VL 27 IS 1 BP 116 EP 125 DI 10.1634/stemcells.2007-0205 PG 10 WC Cell & Tissue Engineering; Biotechnology & Applied Microbiology; Oncology; Cell Biology; Hematology SC Cell Biology; Biotechnology & Applied Microbiology; Oncology; Hematology GA 402SC UT WOS:000263032400014 PM 18403757 ER PT J AU Hayakawa, J Hsieh, MM Uchida, N Phang, O Tisdale, JF AF Hayakawa, Jun Hsieh, Matthew M. Uchida, Naoya Phang, Oswald Tisdale, John F. TI Busulfan Produces Efficient Human Cell Engraftment in NOD/LtSz-Scid IL2R gamma(Null) Mice SO STEM CELLS LA English DT Article DE Cord blood; Peripheral blood stem cell transplantation; Severe combined immunodeficient mice; Transferrin; Xenograft transplant; Busulfan; Erythropoiesis; Hematopoietic stem cells ID HEMATOPOIETIC STEM-CELLS; BLOOD CD34(+) CELLS; BONE-MARROW-CELLS; NOD/SCID MICE; NULL MICE; INTRAFEMORAL TRANSPLANTATION; REPOPULATING ABILITY; CD122(+) CELLS; MODEL; RECEPTOR AB Xenografting immunodeficient mice after low-dose irradiation has been used as a surrogate human hematopoietic stem cell (HSC) assay; however, irradiation requires strict and meticulous animal support and can produce significant mortality rates, limiting the usefulness of this model. In this work, we examined the use of parenteral busulfan as an alternative conditioning agent. Busulfan led to dose-dependent human HSC engraftment in NOD/LtSz-scid/IL2R gamma(null) mice, with marked improvement in survival rates. Terminally differentiated B and T lymphocytes made up most of the human CD45+ cells observed during the initial 5 weeks post-transplant when unselected cord blood (CB) products were infused, suggesting derivation from existing mature elements rather than HSCs. Beyond 5 weeks, CD34+ enriched products produced and sustained superior engraftment rates compared with unselected grafts (CB CD34+, 65.8% +/- 5.35%, vs. whole CB, 4.27% +/- 0.67%, at 24 weeks). CB CD34+ group achieved significantly higher levels of engraftment than mobilized CD34+ enriched peripheral blood (PB CD34+). At 8 weeks, all leukocyte subsets were detected, yet human red blood cells (RBCs) were not observed. Transfused human red cells persisted in the chimeric mice for up to 3 days; an accompanying rise in total bilirubin suggested hemolysis as a contributing factor to their clearance. Recipient mouse-derived human HSCs had the capacity to form erythroid colonies in vitro at various time points post-transplant in the presence of human transferrin (Tf). When human Tf was administered singly or in combination with anti-CD122 antibody and human cytokines, up to 0.1% human RBCs were detectable in the peripheral blood. This long evasive model should prove valuable for the study of human erythroid cells. STEM CELLS 2009; 27: 175-182 C1 [Hayakawa, Jun; Hsieh, Matthew M.; Uchida, Naoya; Phang, Oswald; Tisdale, John F.] Natl Inst Diabet & Digest & Kidney Disorders, Mol & Clin Hematol Branch, Bethesda, MD 20892 USA. [Hayakawa, Jun; Hsieh, Matthew M.; Uchida, Naoya; Phang, Oswald; Tisdale, John F.] NHLBI, NIH, Bethesda, MD 20892 USA. RP Tisdale, JF (reprint author), Natl Inst Diabet & Digest & Kidney Disorders, Mol & Clin Hematol Branch, 9000 Rockville Pike,Bldg 10,Room 9N 116, Bethesda, MD 20892 USA. EM johntis@mail.nih.gov FU Intramural Research Program; NIH; National Institute of Diabetes and Digestive and Kidney Diseases; National Heart, Lung, and Blood Institute FX This research was supported by the Intramural Research Program of the National Institute of Diabetes and Digestive and Kidney Diseases and the National Heart, Lung, and Blood Institute at the NIH. We thank Elizabeth Joyal for collection of the cord blood samples, Martha Kirby for cell sorting, and D. Eric Anderson for mass spectroscopy. This work was supported by the Intramural Research Program of the NIH, National Institute of Diabetes and Digestive and Kidney Diseases. NR 31 TC 24 Z9 24 U1 0 U2 0 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1066-5099 J9 STEM CELLS JI Stem Cells PY 2009 VL 27 IS 1 BP 175 EP 182 DI 10.1634/stemcells.2008-0583 PG 8 WC Cell & Tissue Engineering; Biotechnology & Applied Microbiology; Oncology; Cell Biology; Hematology SC Cell Biology; Biotechnology & Applied Microbiology; Oncology; Hematology GA 402SC UT WOS:000263032400020 PM 18927475 ER PT J AU Nemeth, MJ Mak, KK Yang, YZ Bodine, DM AF Nemeth, Michael J. Mak, Kingston K. Yang, Yingzi Bodine, David M. TI beta-Catenin Expression in the Bone Marrow Microenvironment Is Required for Long-Term Maintenance of Primitive Hematopoietic Cells SO STEM CELLS LA English DT Article DE Wnt; Myeloid Progenitor Cells; Hematopoietic Stem Cells; Transgenic Mice ID WNT SIGNALING PATHWAY; STEM-CELLS; PROGENITOR CELLS; STROMAL CELLS; PARATHYROID-HORMONE; GENE-EXPRESSION; N-CADHERIN; IN-VITRO; MICE; DIFFERENTIATION AB Hematopoiesis is dependent upon the bone marrow microenvironment, which is comprised of multiple mesenchymal cell types, including fibroblasts,endothelial cells, osteoblasts, and stroma progenitors. The canonical Wnt signaling pathway, which relies on the beta-catenin protein to mediate its signal, is necessary for the normal development of mesenchymal tissue. We hypothesized that canonical Wnt signaling regulates the cellular composition and function of the bone marrow microenvironment. We observed that a beta-catenin-deficient bone marrow microenvironment maintained hematopoietic stem cells but exhibited a decreased capacity to support primitive hematopoietic cells. These results correlated with decreased numbers of osteoblasts and with decreased production of basic fibroblast growth factor, stem cell factor, and vascular cell adhesion molecule-1. From these data, we propose a model in which beta-catenin in the microenvironment is required noncell autonomously for long-term maintenance of hematopoietic progenitors. STEM CELLS 2009;27:1109-1119 C1 [Nemeth, Michael J.; Bodine, David M.] NHGRI, Genet & Mol Biol Branch, Bethesda, MD 20892 USA. [Nemeth, Michael J.] Roswell Pk Canc Inst, Dept Med, Buffalo, NY 14263 USA. [Nemeth, Michael J.] Roswell Pk Canc Inst, Dept Immunol, Buffalo, NY 14263 USA. [Mak, Kingston K.; Yang, Yingzi] NHGRI, Genet Dis Res Branch, Bethesda, MD 20892 USA. RP Bodine, DM (reprint author), NHGRI, Genet & Mol Biol Branch, 49 Convent Dr,Rm 4A04, Bethesda, MD 20892 USA. EM tedyaz@nhgri.nih.gov FU Roswell Park Cancer Institute FX We thank Dr. Mark M. Taketo for his generous gift of the Catnblox(ex3)/+ transgenic mouse line. M.J.N. was supported in part by institutional funds provided by Roswell Park Cancer Institute. NR 54 TC 39 Z9 40 U1 1 U2 7 PU ALPHAMED PRESS PI DURHAM PA 318 BLACKWELL ST, STE 260, DURHAM, NC 27701-2884 USA SN 1066-5099 J9 STEM CELLS JI Stem Cells PY 2009 VL 27 IS 5 BP 1109 EP 1119 DI 10.1002/stem.32 PG 11 WC Cell & Tissue Engineering; Biotechnology & Applied Microbiology; Oncology; Cell Biology; Hematology SC Cell Biology; Biotechnology & Applied Microbiology; Oncology; Hematology GA 447GL UT WOS:000266179500014 PM 19415781 ER PT J AU Fliedner, TM Chao, NJ Bader, JL Boettger, A Case, C Chute, J Confer, DL Ganser, A Gorin, NC Gourmelon, P Graessle, DH Krawisz, R Meineke, V Niederwieser, D Port, M Powles, R Sirohi, B Weinstock, DM Wiley, A Coleman, CN AF Fliedner, Theodor M. Chao, Nelson J. Bader, Judith L. Boettger, Axel Case, Cullen, Jr. Chute, John Confer, Dennis L. Ganser, Arnold Gorin, Norbert-Claude Gourmelon, Patrick Graessle, Dieter H. Krawisz, Robert Meineke, Viktor Niederwieser, Dietger Port, Matthias Powles, Ray Sirohi, Bhawna Weinstock, David M. Wiley, Albert Coleman, C. Norman TI Stem Cells, Multiorgan Failure in Radiation Emergency Medical Preparedness: A US/European Consultation Workshop SO STEM CELLS LA English DT Article DE Hemopoietic growth factor; Irradiation; Stem cell transplantation; Stem cell-microenvironment interactions ID HEMATOPOIETIC STEM; NUCLEAR EVENTS; HUMAN EMBRYO; NICHE; BLOOD; MANAGEMENT; EXPOSURE; CONSEQUENCES; RESPONSES; SEVERITY AB The concern of the public regarding terrorist actions involving nuclear emergencies resulted in the reopening of the discussion regarding the best ways to cope with the inevitable health impairments. Medical experts from the US and from Europe considered it of importance to harmonize at an international level the diagnostic and therapeutic approaches regarding the radiation-induced health impairments. The present contribution is the result of the first U.S./European Consultation Workshop addressing approaches to radiation emergency preparedness and assistance, which was held recently at Ulm University, Ulm, Germany. Discussions dealt with the assessment of the extent of damage after total body exposure and, in particular, the quantity and quality of the damage to the hematopoietic stem cell pool. Secondly, the pathogenesis of the multiorgan failure was considered because of the organ-to-organ interactions. Thirdly, approaches were considered to harmonize the "triage-methods'' used on an international level using the "Response Category'' approach as developed for the European Communities. These discussions lead to the conclusion that there is a strong need for continuing education of physicians, nurses, and support personnel to address the issues posed by the management of patients suffering from radiation syndromes. Finally, the discussions expressed the need for more international cooperation in research and development of more refined methods to treat patients with any type of radiation syndromes. STEM CELLS 2009;27:1205-1211 C1 [Chao, Nelson J.; Chute, John] Duke Univ, Div Cellular Therapy, Dept Med, RadCCORE Radiat Countermeasures Ctr Res Excellenc, Durham, NC 27710 USA. [Fliedner, Theodor M.; Graessle, Dieter H.] Univ Ulm, Radiat Med Res Grp, D-89069 Ulm, Germany. [Bader, Judith L.; Coleman, C. Norman] NCI, NIH, Bethesda, MD 20892 USA. [Bader, Judith L.; Coleman, C. Norman] Off Assistant Secretary Preparedness & Response, Dept Hlth & Human Serv, Washington, DC USA. [Boettger, Axel] Fed Minist Environm Nat Protect & Nucl Safety, Dept Radiat Protect, Bonn, Germany. [Case, Cullen, Jr.; Confer, Dennis L.] NMDP, Minneapolis, MN USA. [Ganser, Arnold; Port, Matthias] Hannover Med Sch, Dept Hematol Hemostasis Oncol & Stem Cell Transpl, D-3000 Hannover, Germany. [Gorin, Norbert-Claude] Hosp St Antoine, Dept Hematol & Cell Therapy, Paris, France. [Gourmelon, Patrick] IRSN, Fontenay Aux Roses, France. [Krawisz, Robert] Amer Soc Blood & Marrow Transplantat, Arlington Hts, IL USA. [Meineke, Viktor] Bundeswehr Inst Radiobiol, Munich, Germany. [Niederwieser, Dietger] Univ Leipzig, Dept Hematol & Oncol, Leipzig, Germany. [Powles, Ray] Parkside Oncol Clin, London, England. [Sirohi, Bhawna] Addenbrookes Hosp, Dept Med Oncol, Cambridge, England. [Weinstock, David M.] DFCI, Div Hematol Neoplasia, Boston, MA USA. [Wiley, Albert] Radiat Emergency Assistance Ctr Training Site, Oak Ridge, TN USA. RP Chao, NJ (reprint author), Duke Univ, Div Cellular Therapy, Dept Med, RadCCORE Radiat Countermeasures Ctr Res Excellenc, 2400 Pratt St,Suite 9100, Durham, NC 27710 USA. EM Chao0002@mc.duke.edu RI Port, Matthias/D-5230-2011 FU NIAID NIH HHS [U19 AI067798, U19 AI067798-07] NR 38 TC 23 Z9 23 U1 0 U2 3 PU ALPHAMED PRESS PI DURHAM PA 318 BLACKWELL ST, STE 260, DURHAM, NC 27701-2884 USA SN 1066-5099 J9 STEM CELLS JI Stem Cells PY 2009 VL 27 IS 5 BP 1205 EP 1211 DI 10.1002/stem.16 PG 7 WC Cell & Tissue Engineering; Biotechnology & Applied Microbiology; Oncology; Cell Biology; Hematology SC Cell Biology; Biotechnology & Applied Microbiology; Oncology; Hematology GA 447GL UT WOS:000266179500023 PM 19418462 ER PT J AU Smith, GH Salomon, DS Vonderhar, BK AF Smith, Gilbert H. Salomon, David S. Vonderhar, Barbara K. TI "Evidence that an Early Pregnancy Causes a Persistent Decrease in the Number of Functional Mammary Epithelial Stem Cells-Implications for Pregnancy-Induced Protection Against Breast Cancer'' by Siwko et al. SO STEM CELLS LA English DT Letter ID TUMORIGENESIS; ENVIRONMENT; GLAND; RATS C1 [Smith, Gilbert H.; Salomon, David S.; Vonderhar, Barbara K.] NCI, Mammary Biol & Tumorigenesis Lab, NIH, Bethesda, MD 20892 USA. RP Smith, GH (reprint author), NCI, Mammary Biol & Tumorigenesis Lab, NIH, Bldg37,Rm 1106,MSC4254, Bethesda, MD 20892 USA. EM gs4d@nih.gov NR 6 TC 1 Z9 1 U1 0 U2 1 PU ALPHAMED PRESS PI DURHAM PA 318 BLACKWELL ST, STE 260, DURHAM, NC 27701-2884 USA SN 1066-5099 J9 STEM CELLS JI Stem Cells PY 2009 VL 27 IS 5 BP 1223 EP 1223 DI 10.1002/stem.19 PG 1 WC Cell & Tissue Engineering; Biotechnology & Applied Microbiology; Oncology; Cell Biology; Hematology SC Cell Biology; Biotechnology & Applied Microbiology; Oncology; Hematology GA 447GL UT WOS:000266179500025 PM 19418459 ER PT J AU Blaisdell, CJ Gail, DB Nabel, EG AF Blaisdell, Carol J. Gail, Dorothy B. Nabel, Elizabeth G. TI National Heart, Lung, and Blood Institute Perspective: Lung Progenitor and Stem Cells-Gaps in Knowledge and Future Opportunities SO STEM CELLS LA English DT Article DE Lung cell biology; Lung regeneration; Reprogramming ID SIDE POPULATION CELLS; NEUROEPITHELIAL BODY MICROENVIRONMENT; ENHANCER-BINDING PROTEIN; BONE-MARROW; BRONCHOPULMONARY DYSPLASIA; EPITHELIAL-CELLS; GROWTH-FACTORS; SMOOTH-MUSCLE; BASAL-CELLS; AIRWAY AB Because the lung stem cell field is so new, there remain many unanswered questions that are being addressed regarding the identification, location, and role of exogenous and endogenous stem and progenitor cell populations in growth, regeneration, and repair of the lung. Advancing lung stem cell biology will require multidisciplinary teams and a long term effort to unravel the biologic processes of stem cells in the lung. While no clinical research in lung stem cell therapies are currently funded by NHLBI, the knowledge gained by understanding the basic biology of the lung stem cell populations will be needed to translate to diagnostic and therapeutic strategies in the future. STEM CELLS 2009; 27: 2263-2270 C1 [Blaisdell, Carol J.] NHLBI, NIH, Div Lung Dis, Bethesda, MD 20892 USA. RP Blaisdell, CJ (reprint author), NHLBI, NIH, Div Lung Dis, 6701 Rockledge Dr,10042, Bethesda, MD 20892 USA. EM blaisdellcj@nhlbi.nih.gov NR 54 TC 10 Z9 10 U1 0 U2 0 PU ALPHAMED PRESS PI DURHAM PA 318 BLACKWELL ST, STE 260, DURHAM, NC 27701-2884 USA SN 1066-5099 J9 STEM CELLS JI Stem Cells PY 2009 VL 27 IS 9 BP 2263 EP 2270 DI 10.1002/stem.148 PG 8 WC Cell & Tissue Engineering; Biotechnology & Applied Microbiology; Oncology; Cell Biology; Hematology SC Cell Biology; Biotechnology & Applied Microbiology; Oncology; Hematology GA 497IX UT WOS:000270053700023 PM 19522010 ER PT B AU Smith, GH AF Smith, Gilbert H. BE Bagley, RG Teicher, BA TI Mouse Mammary Tumor Virus: Stem Cells and Mammary Cancer SO STEM CELLS AND CANCER SE Cancer Drug Discovery and Development LA English DT Article; Book Chapter DE Stem cell; MMTV; Mammary; Cancer; Transplantation; Mice ID TEMPLATE DNA STRANDS; EPITHELIAL-CELLS; BREAST-CANCER; CHEMICAL CARCINOGENESIS; TGF-BETA-1 EXPRESSION; GLAND; TUMORIGENESIS; MICE; SENESCENCE; PATHWAYS AB The paradigm of mammary cancer induction by the mouse mammary tumor virus (MMTV) is used to illustrate the body of evidence that supports the hypothesis that mammary epithelial stem/progenitor cells represent targets for oncogenic transformation. It is argued that this is not a special case applicable only to MMTV-induced mammary cancer, because MMTV acts as an environmental mutagen producing random interruptions in the somatic DNA of infected cells by insertion of proviral DNA copies. In addition to disrupting the host genome, the proviral DNA also influences gene expression through its associated enhancer sequences over significant intergenomic distances. Genes commonly affected by MMTV insertion in multiple individual tumors include, the Writ genes, the FGF gene family, and the Notch gene family. All of these gene families are known to play essential roles in stem cell maintenance and behavior in a variety of organs. The MMTV-induced mutations accumulate in cells that are long lived and possess the properties of stem cells, namely, self-renewal and the capacity to produce divergent epithelial progeny through asymmetric division. The evidence shows that epithelial cells with these properties are present in normal mammary glands, may be infected with MMTV, and become transformed to produce epithelial hyperplasia through MMTV-induced mutagenesis and progress to frank mammary malignancy. Retroviral marking via MMTV proviral insertion demonstrates that this process progresses from a single mammary epithelial cell that possesses all of the features ascribed to tissue-specific stem cells. C1 NCI, Mammary Biol & Tumorigenesis Lab, Ctr Canc Res, Bethesda, MD 20892 USA. RP Smith, GH (reprint author), NCI, Mammary Biol & Tumorigenesis Lab, Ctr Canc Res, Bethesda, MD 20892 USA. NR 43 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 BN 978-1-60327-932-1 J9 CANCER DRUG DISCOV D JI Canc. Drug. Disc. Dev. PY 2009 BP 127 EP 140 DI 10.1007/978-1-60327-933-8_10 D2 10.1007/978-1-60327-933-8 PG 14 WC Oncology; Pharmacology & Pharmacy SC Oncology; Pharmacology & Pharmacy GA BKK41 UT WOS:000268379100010 ER PT S AU Marotta, F Yadav, H Pathak, S Minelli, E Signorelli, P Lorenzetti, A Marandola, P AF Marotta, F. Yadav, H. Pathak, S. Minelli, E. Signorelli, P. Lorenzetti, A. Marandola, P. BE Bradlow, HL Carruba, G TI Inhibition of Human Breast Cancer Cell Growth and Enzymatic Activity by a Fermented Nutraceutical SO STEROID ENZYMES AND CANCER SE ANNALS OF THE NEW YORK ACADEMY OF SCIENCES LA English DT Article; Proceedings Paper CT 9th Advanced Course on Steroid Enzymes and Cancer CY MAY 03-08, 2008 CL Erice, ITALY DE breast cancer cell lines; in vivo breast cancer model; Manda-Koso ID BCL-2; ANTIOXIDANT; CARCINOMA; APOPTOSIS AB Human breast cancer cell lines MCF-7 (ER-positive) and Hs578T (ER-negative) were cultured and one lot incubated for 48 It with 5-50 mu g/ml of a fermented phytocompound (MK: Manda-Koso, Innoshima, Japan). lit vitro, it appeared a dose-dependent decrease of cell viability (5-57%) in MK group in both cell lines (P < 0.001, plateau: 30 mu g/ml), decreased beta-galactosidase activity, enhanced apoptosis, and inversely increased Bax/Bcl2 ratio (P < 0.01) with an upregulation of p53 (P < 0.05). In the ill vivo model, Balb-c mice were inoculated with tumor cells and the treatment group was fed with 20 mg of MK. Tumor weight in MK-fed group was time-course reduced by 22%, to 51% at 2 and 4 weeks, respectively (P < 0.05) with increased survival (P < 0.05). Tumour tissue of MK-fed mice showed a downregulated Bcl-2 with increased Bax/Bcl-2 ratio, reduced PCNA, and activated caspase 3. Although more studies are ongoing to foster the clinical applicability of MK integrated within a rational chemopreventive and therapeutic strategy, a p53-triediated mechanism is likely to play a relevant role, besides its reported antioxidant capacity, NK cell activity enhancement, cancer-cytostatic activity properties. C1 [Marotta, F.; Signorelli, P.; Lorenzetti, A.; Marandola, P.] GAIA Age Management Fdn, Nutraceut Nutrigenom Unit, Pavia, Italy. [Yadav, H.] NIDDK, NIH, Bethesda, MD 20892 USA. [Pathak, S.] Univ Kalyani, Cytogenet & Mol Biol Lab, Kalyani 741235, W Bengal, India. [Marotta, F.; Minelli, E.] Univ Milan, WHO Ctr Biotech & Nat Med, Milan, Italy. RP Marotta, F (reprint author), Piazza Firenze 12, I-20151 Milan, Italy. EM fmarchimede@libero.it NR 15 TC 1 Z9 1 U1 0 U2 2 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXEN, ENGLAND SN 0077-8923 BN 978-1-57331-745-0 J9 ANN NY ACAD SCI JI Ann.NY Acad.Sci. PY 2009 VL 1155 BP 273 EP 277 DI 10.1111/j.1749-6632.2008.03684.x PG 5 WC Oncology; Multidisciplinary Sciences SC Oncology; Science & Technology - Other Topics GA BJC65 UT WOS:000264751500031 PM 19250216 ER PT B AU Wang, PY Wenthold, RJ AF Wang, Philip Y. Wenthold, Robert J. BE Hortsch, M Umemori, H TI Synaptic Adhesion-Like Molecules (SALMs) SO STICKY SYNAPSE: CELL ADHESION MOLECULES AND THEIR ROLE IN SYNAPSE FORMATION AND MAINTENANCE LA English DT Article; Book Chapter DE Synapse; Dendrite; Axon; PDZ proteins; LRR; Growth cone; Heteromeric; Homomeric; Neurite outgrowth ID LONG-TERM POTENTIATION; LEUCINE-RICH REPEATS; CELL-ADHESION; NEURITE OUTGROWTH; EXCITATORY SYNAPSES; GROWTH CONE; N-CADHERIN; TRANSMEMBRANE PROTEINS; DENDRITE ARBORIZATION; RECEPTOR TRAFFICKING AB The synaptic adhesion-like molecules (SALMs) are a newly discovered family of cell adhesion molecules that have a variety of functions in neuronal development, including aspects of neurite Outgrowth and synapse formation (Ko et al. Neuron 50:233-245, 2006, Morimura et al. Gene 380:72-83, 2006, Wang et al. J Neurosci 26:2174-2183, 2006, Seabold et al. J Biol Chem 283:8395-8405, 2008, Wang et al. Mol Cell Neurosci, 39:83-94, 2008). Also known as Lrfn (leucine-rich and fibronectin III domain-containing), five family members have been identified thus far: SALM1/Lrfn2, SALM2/Lrfn1, SALM3/Lrfn4, SALM4/Lrfn3, and SALM5/Lrfn5. The SALMs have been shown to interact with NMDA receptors and the PSD-95 family of MAGUK proteins. Recent studies also indicate that the individual SALMs, while similar in structure, play distinct roles in heteromeric and homomeric protein interactions and neurite outgrowth (Seabold et al. J Blot Chem 283:8395-8405, 2008, Wang et al. Mol Cell Neurosci, 39:83-94, 2008). Neurite outgrowth and synapse formation are fundamental mechanisms in the development of the nervous System. While a considerable amount of information is known about both phenomena, the mechanism connecting the two is still enigmatic. SALMs join a growing mosaic of synaptic proteins that contribute to both neurite outgrowth and synapse formation during the course of development. Investigating SALMs and related proteins is essential for addressing fundamental questions of neuronal development. C1 [Wang, Philip Y.; Wenthold, Robert J.] Natl Inst Deafness & Other Commun Disorders, Neurochem Lab, NIH, Bethesda, MD 20892 USA. [Wang, Philip Y.] Univ Maryland, Coll Chem & Life Sci, Dept Biol, College Pk, MD 20742 USA. [Wang, Philip Y.] Univ Maryland, Neurosci & Cognit Sci Program, College Pk, MD 20742 USA. RP Wenthold, RJ (reprint author), Natl Inst Deafness & Other Commun Disorders, Neurochem Lab, NIH, Bethesda, MD 20892 USA. EM wenthold@nidcd.nih.gov NR 67 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013, UNITED STATES BN 978-0-387-92707-7 PY 2009 BP 367 EP 383 DI 10.1007/978-0-387-92708-4_18 D2 10.1007/978-0-387-92708-4 PG 17 WC Cell Biology; Neurosciences SC Cell Biology; Neurosciences & Neurology GA BKY34 UT WOS:000269610400018 ER PT B AU Chitakornkijsil, P AF Chitakornkijsil, Pranee BE Xiaowen, J Erming, X Schneider, I TI SMEs Entrepreneurship and Development Strategies SO STRATEGIC MANAGEMENT ENGINEERING: ENTERPRISE, ENVIRONMENT AND CRISIS LA English DT Proceedings Paper CT International Conference on Strategic Management CY JUN 25-30, 2009 CL Chengdu, PEOPLES R CHINA DE SMEs; International Entrepreneurship; Export; Import; International Market Place AB In this study, the method for SMEs to go international is considered. The study shows the new international development to expand for international market. Besides, it introduces how entrepreneurs are able to take advantage of exporting opportunities. Moreover it illustrates the entrepreneurial benefits of importing. In addition, it explains the benefits of foreign direct investment by entrepreneur. More than that, it demonstrates the disadvantages and advantages of entrepreneurial joint ventures. Furthermore, it exhibits advantages and disadvantages of licensing arrangements. Eventually, it establishes key steps for enhancing the international market place. C1 [Chitakornkijsil, Pranee] NIDA, Grad Sch Business Adm, Bangkok 10240, Thailand. NR 36 TC 0 Z9 0 U1 0 U2 1 PU SICHUAN UNIV PRESS PI CHENGDU PA 29 WANGJIANGLU, JIUYANQIAO, CHENGDU, PEOPLES R CHINA BN 978-7-5614-4376-7 PY 2009 BP 214 EP 218 PG 5 WC Business; Business, Finance; Economics; Management SC Business & Economics GA BKP51 UT WOS:000268879300027 ER PT J AU Biddie, SC Hager, GL AF Biddie, Simon C. Hager, Gordon L. TI Glucocorticoid receptor dynamics and gene regulation SO STRESS-THE INTERNATIONAL JOURNAL ON THE BIOLOGY OF STRESS LA English DT Review DE Glucocorticoid receptor; chromatin; dynamics; gene expression ID MAMMARY-TUMOR VIRUS; NF-KAPPA-B; LONG TERMINAL REPEAT; IN-VIVO; ESTROGEN-RECEPTOR; LIVING CELLS; TRANSCRIPTIONAL ACTIVATION; MOLECULAR CHAPERONES; TRANSACTIVATION DOMAIN; CHROMATIN DYNAMICS AB The glucocorticoid receptor regulates the expression of a large number of genes in mammalian cells. The interaction of this receptor with regulatory elements has been discovered to be highly dynamic, with occupancy states measured in seconds, rather than minutes or hours. This finding has led to a paradigm shift in our understanding of receptor function throughout the genome. The mechanisms involved in these rapid exchange events, as well as the implications for receptor function, are discussed. C1 [Biddie, Simon C.; Hager, Gordon L.] NCI, Lab Receptor Biol & Gene Express, NIH, Bethesda, MD 20892 USA. [Biddie, Simon C.] Univ Bristol, Dept Med, Henry Wellcome Labs Integrat Neurosci & Endocrino, Bristol BS1 3NY, Avon, England. RP Hager, GL (reprint author), NCI, Lab Receptor Biol & Gene Express, NIH, Bldg 41,B602,41 Lib Dr, Bethesda, MD 20892 USA. EM hagerg@exchange.nih.gov OI Biddie, Simon/0000-0002-8253-0253 FU Intramural Research Program; NIH, National Cancer Institute; Center for Cancer Research FX S. C. B was supported, in part, by The Needham Cooper Postgraduate Medicine Scholarship held by Stafford L. Lightman and the Faculty of Medicine, University of Bristol. This research was supported by the Intramural Research Program of the NIH, National Cancer Institute, Center for Cancer Research. NR 109 TC 37 Z9 38 U1 1 U2 5 PU TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXON, ENGLAND SN 1025-3890 J9 STRESS JI Stress PY 2009 VL 12 IS 3 BP 193 EP 205 AR PII 906263195 DI 10.1080/10253890802506409 PG 13 WC Behavioral Sciences; Endocrinology & Metabolism; Neurosciences SC Behavioral Sciences; Endocrinology & Metabolism; Neurosciences & Neurology GA 438VK UT WOS:000265583600001 PM 19051126 ER PT J AU Ali, M Atula, S Bath, PMW Grotta, J Hacke, W Lyden, P Marler, JR Sacco, RL Lees, KR AF Ali, Myzoon Atula, Sari Bath, Philip M. W. Grotta, James Hacke, Werner Lyden, Patrick Marler, John R. Sacco, Ralph L. Lees, Kennedy R. CA VISTA Investigators TI Stroke Outcome in Clinical Trial Patients Deriving From Different Countries SO STROKE LA English DT Article DE acute care; clinical trials; database; epidemiology; outcomes ID ACUTE ISCHEMIC-STROKE; CASE-FATALITY; RISK-FACTORS; MONICA PROJECT; EUROPEAN PERSPECTIVE; SOCIOECONOMIC-STATUS; NORTHERN MANHATTAN; WIDENING GAP; MORTALITY; CARE AB Background and Purpose-Stroke incidence and outcome vary widely within and across geographical locations. We examined whether differences in index stroke severity, stroke risk factors, mortality, and stroke outcome across geographical locations remain after adjusting for case mix. Methods-We analyzed 3284 patients from the Virtual International Stroke Trials Archive (VISTA). We used logistic regression to examine the incidence of mild index stroke, functional, and neurological outcomes after accounting for age, medical history, year of trial recruitment, and initial stroke severity in the functional and neurological outcome analyses. We examined mortality between geographical regions using a Cox proportional hazards model, accounting for age, initial stroke severity, medical history, and year of trial recruitment. Results-Patients enrolled in the USA and Canada had the most severe index strokes. Those recruited in Austria and Switzerland had the best functional and neurological outcomes at 90 days (P<0.05), whereas those enrolled in Germany had the worst functional outcome at 90 days (P=0.013). Patients enrolled in Austria, Switzerland, Belgium, Netherlands, Finland, Germany, Greece, Israel, Spain, and Portugal had a significantly better survival rate when compared with those enrolled in USA and Canada. Patients enrolled in trials after 1998 had more severe index strokes, with no significant difference in outcome compared with those enrolled before 1998. Conclusion-We identified regional variations in index stroke severity, outcome, and mortality for patients enrolled in ischemic stroke clinical trials over the past 13 years that were not fully explained by case mix. Index stroke severity was greater in patients enrolled after 1998, with no significant improvement in outcomes compared to those enrolled before 1998. (Stroke. 2009;40:35-40.) C1 [Ali, Myzoon; Atula, Sari; Lees, Kennedy R.] Univ Glasgow, Western Infirm, Gardiner Inst, Dept Med & Therapeut, Glasgow G11 6NT, Lanark, Scotland. [Bath, Philip M. W.] Univ Nottingham, Div Stroke Med, Nottingham NG7 2RD, England. [Grotta, James] Univ Texas Houston, Houston Med Sch, Dept Neurol, Houston, TX USA. [Hacke, Werner] Univ Heidelberg, Dept Neurol, D-6900 Heidelberg, Germany. [Lyden, Patrick] Univ Calif San Diego, San Diego, CA 92103 USA. [Lyden, Patrick] VA Stroke Ctr, San Diego, CA USA. [Marler, John R.] Natl Inst Neurol Disorders & Stroke, Bethesda, MD USA. [Sacco, Ralph L.] Univ Miami, Miller Sch Med, Miami, FL 33136 USA. RP Ali, M (reprint author), Univ Glasgow, Western Infirm, Gardiner Inst, Univ Dept Med & Therapeut,Div Cardiovasc & Med Sc, 44 Church St, Glasgow G11 6NT, Lanark, Scotland. EM myzoonali@clinmed.gla.ac.uk RI Bath, Philip/F-9020-2011; Davis, Stephen/L-5260-2013; OI Bath, Philip/0000-0003-2734-5132; Davis, Stephen/0000-0003-0962-2300; Gregson, Barbara/0000-0003-4868-9137; Kaste, Markku/0000-0001-6557-6412 NR 43 TC 23 Z9 25 U1 0 U2 3 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 2009 VL 40 IS 1 BP 35 EP 40 DI 10.1161/STROKEAHA.108.518035 PG 6 WC Clinical Neurology; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA 388ZN UT WOS:000262059400009 PM 18927457 ER PT J AU Ay, H Arsava, EM Johnston, SC Vangel, M Schwamm, LH Furie, KL Koroshetz, WJ Sorensen, AG AF Ay, Hakan Arsava, E. Murat Johnston, S. Claiborne Vangel, Mark Schwamm, Lee H. Furie, Karen L. Koroshetz, Walter J. Sorensen, A. Gregory TI Clinical- and Imaging-Based Prediction of Stroke Risk After Transient Ischemic Attack The CIP Model SO STROKE LA English DT Article DE diffusion-weighted imaging; stroke risk; transient ischemic attack ID DIFFUSION-WEIGHTED MRI; MINOR STROKE; TIA PATIENTS; ABCD SCORE; EMERGENCY; PREVALENCE; LESIONS; VALIDATION AB Background and Purpose-Predictive instruments based on clinical features for early stroke risk after transient ischemic attack suffer from limited specificity. We sought to combine imaging and clinical features to improve predictions for 7-day stroke risk after transient ischemic attack. Methods-We studied 601 consecutive patients with transient ischemic attack who had MRI within 24 hours of symptom onset. A logistic regression model was developed using stroke within 7 days as the response criterion and diffusion-weighted imaging findings and dichotomized ABCD(2) score (ABCD(2) >= 4) as covariates. Results-Subsequent stroke occurred in 25 patients (5.2%). Dichotomized ABCD(2) score and acute infarct on diffusion-weighted imaging were each independent predictors of stroke risk. The 7-day risk was 0.0% with no predictor, 2.0% with ABCD(2) score >= 4 alone, 4.9% with acute infarct on diffusion-weighted imaging alone, and 14.9% with both predictors (an automated calculator is available at http://cip. martinos. org). Adding imaging increased the area under the receiver operating characteristic curve from 0.66 (95% CI, 0.57 to 0.76) using the ABCD(2) score to 0.81 (95% CI, 0.74 to 0.88; P = 0.003). The sensitivity of 80% on the receiver operating characteristic curve corresponded to a specificity of 73% for the CIP model and 47% for the ABCD(2) score. Conclusions-Combining acute imaging findings with clinical transient ischemic attack features causes a dramatic boost in the accuracy of predictions with clinical features alone for early risk of stroke after transient ischemic attack. If validated in relevant clinical settings, risk stratification by the CIP model may assist in early implementation of therapeutic measures and effective use of hospital resources. (Stroke. 2009; 40: 181-186.) C1 [Ay, Hakan; Schwamm, Lee H.; Furie, Karen L.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Neurol,Stroke Serv, Charlestown, MA 02129 USA. [Ay, Hakan; Arsava, E. Murat; Vangel, Mark; Sorensen, A. Gregory] Harvard Univ, Massachusetts Gen Hosp, Sch Med, AA Martinos Ctr Biomed Imaging,Dept Radiol, Charlestown, MA 02129 USA. [Johnston, S. Claiborne] Univ Calif San Francisco, Dept Neurol, San Francisco, CA 94143 USA. [Johnston, S. Claiborne] Univ Calif San Francisco, Dept Epidemiol & Biostat, San Francisco, CA 94143 USA. [Koroshetz, Walter J.] NINDS, NIH, Bethesda, MD USA. RP Ay, H (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Neurol,Stroke Serv, 149 13th St,Room 2301, Charlestown, MA 02129 USA. EM hay@partners.org RI Arsava, Ethem Murat/I-9197-2013; OI Arsava, Ethem Murat/0000-0002-6527-4139; Schwamm, Lee/0000-0003-0592-9145 FU NIH [R01-NS38477-04, P41-RR14075]; [USPHSNS38477] FX This work was supported by USPHSNS38477 and NIH grants R01-NS38477-04 and P41-RR14075. NR 34 TC 78 Z9 91 U1 1 U2 9 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 2009 VL 40 IS 1 BP 181 EP 186 DI 10.1161/STROKEAHA.108.521476 PG 6 WC Clinical Neurology; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA 388ZN UT WOS:000262059400032 PM 18948609 ER PT J AU Schoch, CL Crous, PW Groenewald, JZ Boehm, EWA Burgess, TI de Gruyter, J de Hoog, GS Dixon, LJ Grube, M Gueidan, C Harada, Y Hatakeyama, S Hirayama, K Hosoya, T Huhndorf, SM Hyde, KD Jones, EBG Kohlmeyer, J Kruys, A Li, YM Lucking, R Lumbsch, HT Marvanova, L Mbatchou, JS Mcvay, AH Miller, AN Mugambi, GK Muggia, L Nelsen, MP Nelson, P Owensby, CA Phillips, AJL Phongpaichit, S Pointing, SB Pujade-Renaud, V Raja, HA Plata, ER Robbertse, B Ruibal, C Sakayaroj, J Sano, T Selbmann, L Shearer, CA Shirouzu, T Slippers, B Suetrong, S Tanaka, K Volkmann-Kohlmeyer, B Wingfield, MJ Wood, AR Woudenberg, JHC Yonezawa, H Zhang, Y Spatafora, JW AF Schoch, C. L. Crous, P. W. Groenewald, J. Z. Boehm, E. W. A. Burgess, T. I. de Gruyter, J. de Hoog, G. S. Dixon, L. J. Grube, M. Gueidan, C. Harada, Y. Hatakeyama, S. Hirayama, K. Hosoya, T. Huhndorf, S. M. Hyde, K. D. Jones, E. B. G. Kohlmeyer, J. Kruys, A. Li, Y. M. Lucking, R. Lumbsch, H. T. Marvanova, L. Mbatchou, J. S. McVay, A. H. Miller, A. N. Mugambi, G. K. Muggia, L. Nelsen, M. P. Nelson, P. Owensby, C. A. Phillips, A. J. L. Phongpaichit, S. Pointing, S. B. Pujade-Renaud, V. Raja, H. A. Plata, E. Rivas Robbertse, B. Ruibal, C. Sakayaroj, J. Sano, T. Selbmann, L. Shearer, C. A. Shirouzu, T. Slippers, B. Suetrong, S. Tanaka, K. Volkmann-Kohlmeyer, B. Wingfield, M. J. Wood, A. R. Woudenberg, J. H. C. Yonezawa, H. Zhang, Y. Spatafora, J. W. TI A class-wide phylogenetic assessment of Dothideomycetes SO STUDIES IN MYCOLOGY LA English DT Review DE Ascomycota; Pezizomycotina; Dothideomyceta; fungal evolution; lichens; multigene phylogeny; phylogenomics; plant pathogens; saprobes; Tree of Life ID RIBOSOMAL DNA-SEQUENCES; MULTIGENE PHYLOGENIES; MOLECULAR PHYLOGENY; MAXIMUM-LIKELIHOOD; MULTIPLE ALIGNMENT; MARINE ASCOMYCOTA; RDNA SEQUENCES; FUNGI; EVOLUTION; CLASSIFICATION AB We present a comprehensive phylogeny derived from 5 genes, nucSSU, nucLSU rDNA, TEF1, RPB1 and RPB2, for 356 isolates and 41 families (six newly described in this volume) in Dothideomycetes. All currently accepted orders in the class are represented for the first time in addition to numerous previously unplaced lineages. Subclass Pleosporomycelidae is expanded to include the aquatic order Jahnulales. An ancestral reconstruction of basic nutritional modes supports numerous transitions from saprobic life histories to plant associated and lichenised modes and a transition from terrestrial to aquatic habitats are confirmed. Finally, a genomic comparison of 6 dothideomycete genomes with other fungi finds a high level of unique protein associated with the class, supporting its delineation as a separate taxon. C1 [Schoch, C. L.; Robbertse, B.] NIH, Natl Ctr Biotechnol Informat, Natl Lib Med, Bethesda, MD 20892 USA. [Crous, P. W.; Groenewald, J. Z.; de Gruyter, J.; de Hoog, G. S.; Gueidan, C.; Woudenberg, J. H. C.] CBS KNAW Fungal Biodivers Ctr, NL-3508 AD Utrecht, Netherlands. [Boehm, E. W. A.] Kean Univ, Dept Biol Sci, Union, NJ 07083 USA. [Burgess, T. I.] Murdoch Univ, Murdoch, WA 6150, Australia. [de Gruyter, J.] Plant Protect Serv, NL-6700 HC Wageningen, Netherlands. [Dixon, L. J.] USDA ARS, Systemat Mycol & Microbiol Lab, Beltsville, MD 20705 USA. [Grube, M.; Muggia, L.] Karl Franzens Univ Graz, Inst Plant Sci, Graz, Austria. [Harada, Y.; Hatakeyama, S.; Hirayama, K.; Sano, T.; Tanaka, K.; Yonezawa, H.] Hirosaki Univ, Fac Agr & Life Sci, Aomori 0368561, Japan. [Hosoya, T.] Natl Museum Nat & Sci, Tsukuba, Ibaraki 3050005, Japan. [Huhndorf, S. M.; Lucking, R.; Lumbsch, H. T.; Mbatchou, J. S.; Mugambi, G. K.; Nelsen, M. P.; Plata, E. Rivas] Field Museum, Dept Bot, Chicago, IL 60605 USA. [Hyde, K. D.] Mae Fah Luang Univ, Sch Sci 17, Muang 57100, Chiang Rai, Thailand. [Jones, E. B. G.; Sakayaroj, J.; Suetrong, S.] Natl Ctr Genet Engn & Biotechnol BIOTEC, Bioresources Technol Unit, Khlong Luang 12120, Pathum Thani, Thailand. [Kohlmeyer, J.; Volkmann-Kohlmeyer, B.] Univ N Carolina Chapel Hill, Inst Marine Sci, Morehead City, NC 28557 USA. [Kruys, A.] Uppsala Univ, Evolutionary Biol Ctr, Dept Systemat Biol, SE-75236 Uppsala, Sweden. [Marvanova, L.] Masaryk Univ, Fac Sci, Inst Expt Biol, CZ-60200 Brno, Czech Republic. [Mbatchou, J. S.] Depaul Univ, Coll Liberal Arts & Sci, Chicago, IL 60604 USA. [McVay, A. H.; Owensby, C. A.; Spatafora, J. W.] Oregon State Univ, Dept Bot & Plant Pathol, Corvallis, OR 97331 USA. [Miller, A. N.] Univ Illinois, Illinois Nat Hist Survey, Champaign, IL 61820 USA. [Mugambi, G. K.] Natl Museums Kenya, Dept Bot, Nairobi 00100, Kenya. [Nelsen, M. P.] Univ Chicago, Comm Evolutionary Biol, Chicago, IL 60637 USA. [Nelson, P.] Univ Minnesota, St Paul, MN 55108 USA. [Phillips, A. J. L.] Univ Nova Lisboa, Fac Ciencias & Tecnol, Dept Ciencias Vida, Ctr Recursos Microbiol, P-2829516 Quinta Da Torre, Caparica, Portugal. [Phongpaichit, S.; Suetrong, S.] Prince Songkia Univ, Fac Sci, Dept Microbiol, Hat Yai 90112, Songkhla, Thailand. [Pointing, S. B.; Zhang, Y.] Univ Hong Kong, Sch Biol Sci, Div Microbiol, Hong Kong, Hong Kong, Peoples R China. [Pujade-Renaud, V.] Univ Clermont Ferrand, CIRAD PIAF, F-63177 Aubiere, France. [Raja, H. A.; Shearer, C. A.] Univ Illinois, Dept Plant Biol, Urbana, IL 61801 USA. [Mugambi, G. K.; Plata, E. Rivas] Univ Illinois, Dept Biol Sci, Chicago, IL 60607 USA. [Ruibal, C.] Univ Politecn Madrid, Escuela Tecn Super Ingenieros Ind, Dept Ingn & Ciencia Mat, E-28006 Madrid, Spain. [Selbmann, L.] Largo Univ, Univ Tuscia, DECOS, Viterbo, Italy. [Shirouzu, T.] Tottori Univ, Fungus Mushroom Resource & Res Ctr, Tottori 6808553, Japan. [Slippers, B.; Wingfield, M. J.] Univ Pretoria, Fac Nat & Agr Sci, Dept Genet, Ctr Excellence Tree Hlth Biotechnol,FABI, ZA-0002 Pretoria, South Africa. [Wood, A. R.] ARC Plant Protect Res Inst, ZA-7599 Stellenbosch, South Africa. [Hyde, K. D.; Li, Y. M.] Chinese Acad Forestry, Res Inst Resource Insects, Int Fungal Res Dev Ctr, Kunming, Yunnan, Peoples R China. RP Schoch, CL (reprint author), NIH, Natl Ctr Biotechnol Informat, Natl Lib Med, 45 Ctr Dr,MSC 6510, Bethesda, MD 20892 USA. EM schoch2@ncbi.nlm.nih.gov RI REQUIMTE, MM/M-6160-2013; REQUIMTE, UCIBIO/N-9846-2013; Gueidan, Cecile/C-8803-2014; Phillips, Alan/C-6102-2011; Slippers, Bernard/A-9351-2008; Groenewald, Johannes/F-4667-2011; Sakayaroj, Jariya/D-1845-2012; Crous, Pedro/H-1489-2012; Schoch, Conrad/J-4825-2012; Lumbsch, Thorsten/K-3573-2012; Wingfield, Michael/A-9473-2008; Jones, Gareth/C-5137-2013; Woudenberg, Joyce H.C./C-9384-2013; Tanaka, Kazuaki/F-1924-2013; Burgess, Treena/G-4770-2011; Selbmann, Laura/L-3056-2013 OI Raja, Huzefa/0000-0002-0824-9463; Ruibal Villasenor, Constantino/0000-0003-3494-7051; Grube, Martin/0000-0001-6940-5282; Phillips, Alan/0000-0001-6367-9784; Slippers, Bernard/0000-0003-1491-3858; Crous, Pedro/0000-0001-9085-8825; Lumbsch, Thorsten/0000-0003-1512-835X; Woudenberg, Joyce H.C./0000-0002-7337-6864; Burgess, Treena/0000-0002-7962-219X; FU NIH; National Library of Medicine; NSF [DEB-0717476, DEB-0732993] FX Authors from individual papers in this volume contributed to this work and specific acknowledgements to that regard can be found in individual papers. Work performed for this paper by the first author after 2008 was supported in part by the Intramural Research Program of the NIH, National Library of Medicine. Part of this work was also funded by grants from NSF (DEB-0717476) to J. W. Spatafora (and C.L. Schoch until 2008) and (DEB-0732993) to J.W. Spatafora and B. Robbertse. NR 107 TC 212 Z9 214 U1 9 U2 59 PU CENTRAALBUREAU SCHIMMELCULTURE PI UTRECHT PA PO BOX 85167, 3508 AD UTRECHT, NETHERLANDS SN 0166-0616 J9 STUD MYCOL JI Stud. Mycol. PY 2009 IS 64 BP 1 EP 15 DI 10.3114/sim.2009.64.01 PG 15 WC Mycology SC Mycology GA 553KQ UT WOS:000274365900002 ER PT J AU Crous, PW Schoch, CL Hyde, KD Wood, AR Gueidan, C de Hoog, GS Groenewald, JZ AF Crous, P. W. Schoch, C. L. Hyde, K. D. Wood, A. R. Gueidan, C. de Hoog, G. S. Groenewald, J. Z. TI Phylogenetic lineages in the Capnodiales SO STUDIES IN MYCOLOGY LA English DT Review DE Ascomycetes; Brunneosphaerella; Capnodiales; DNA sequence comparisons; Mycosphaerella; novel primers; systematics ID RIBOSOMAL DNA-SEQUENCES; LEAF SPOTS; GEN-NOV; FUNGAL PATHOGENS; LICHENIZED FUNGI; BLOTCH-DISEASE; CROFTON WEED; SOUTH-AFRICA; MYCOSPHAERELLA; EUCALYPTUS AB The Capnodiales incorporates plant and human pathogens, endophytes, saprobes and epiphytes, with a wide range of nutritional modes. Several species are lichenised, or occur as parasites on fungi, or animals. The aim of the present study was to use DNA sequence data of the nuclear ribosomal small and large subunit RNA genes to test the monophyly of the Capnodiales, and resolve families within the order. We designed primers to allow the amplification and sequencing of almost the complete nuclear ribosomal small and large subunit RNA genes. Other than the Capnodiaceae (sooty moulds), and the Davidiellaceae, which contains saprobes and plant pathogens, the order presently incorporates families of major plant pathological importance such as the Mycosphaerellaceae, Teratosphaeriaceae and Schizothyriaceae. The Piedraiaceae was not supported, but resolves in the Teratosphaeriaceae. The Dissoconiaceae is introduced as a new family to accommodate Dissoconium and Ramichloridium. Lichenisation, as well as the ability to be saprobic or plant pathogenic evolved more than once in several families, though the taxa in the upper clades of the tree lead us to conclude that the strictly plant pathogenic, nectrotrophic families evolved from saprobic ancestors (Capnodiaceae), which is the more primitive state. C1 [Crous, P. W.; Gueidan, C.; de Hoog, G. S.; Groenewald, J. Z.] CBS KNAW Fungal Biodivers Ctr, NL-3508 AD Utrecht, Netherlands. [Crous, P. W.] Univ Wageningen & Res Ctr, Phytopathol Lab, NL-6708 PB Wageningen, Netherlands. [Schoch, C. L.] NIH, Natl Ctr Biotechnol Informat, Natl Lib Med, Bethesda, MD 20892 USA. [Wood, A. R.] ARC Plant Protect Res Inst, ZA-7599 Stellenbosch, South Africa. [Hyde, K. D.] Mae Fah Luang Univ, Sch Sci, Muang 57100, Chiang Rai, Thailand. RP Crous, PW (reprint author), CBS KNAW Fungal Biodivers Ctr, POB 85167, NL-3508 AD Utrecht, Netherlands. EM p.crous@cbs.knaw.nl RI Groenewald, Johannes/F-4667-2011; Crous, Pedro/H-1489-2012; Schoch, Conrad/J-4825-2012; Gueidan, Cecile/C-8803-2014 OI Crous, Pedro/0000-0001-9085-8825; FU NIH; National Library of Medicine; NSF [DEB-0717476] FX Several colleagues have helped to collect material studied here, without which this work would not have been possible. Drs E.H.C. Mckenzie and S.R. Pennycook (Landcare New Zealand) are specifically thanked for recollecting Phaeophleospora atkinsonfi. We are grateful to BIOTEC and Dr Lily Eurwilaichitr (Director, Bioresources unit, BIOTEC) for assisting with a collection trip in Thailand under the collaborative BIOTEC-CBS memorandum of understanding. We thank Miss Marjan Vermaas for preparing the photographic plates, and M. Starink-Willemse, and A. van lperen, for assistance with DNA sequencing and fungal cultures. Work performed for this paper by the second author after 2008 was supported in part by the Intramural Research Program of the NIH, National Library of Medicine. Before 2008 work was funded by a grant from NSF (DEB-0717476). We are grateful to Drs Roland Kirschner, Alan J. Phillips and Treena I. Burgess for their critical comments on this script. The views expressed, however, are those of the authors. NR 121 TC 147 Z9 153 U1 1 U2 22 PU CENTRAALBUREAU SCHIMMELCULTURE PI UTRECHT PA UPPSALALAAN 8, 3584 CT UTRECHT, NETHERLANDS SN 0166-0616 J9 STUD MYCOL JI Stud. Mycol. PY 2009 IS 64 BP 17 EP 47 DI 10.3114/sim.2009.64.02 PG 31 WC Mycology SC Mycology GA 553KQ UT WOS:000274365900003 PM 20169022 ER PT J AU Boehm, EWA Mugambi, GK Miller, AN Huhndorf, SM Marincowitz, S Spatafora, JW Schoch, CL AF Boehm, E. W. A. Mugambi, G. K. Miller, A. N. Huhndorf, S. M. Marincowitz, S. Spatafora, J. W. Schoch, C. L. TI A molecular phylogenetic reappraisal of the Hysteriaceae, Mytilinidiaceae and Gloniaceae (Pleosporomycetidae, Dothideomycetes) with keys to world species SO STUDIES IN MYCOLOGY LA English DT Review DE Evolution; fungi; Hysteriales; Mytilinidiales; Patellariales; phylogeny; speciation; taxonomy ID RUSSIAN FAR-EAST; RIBOSOMAL DNA-SEQUENCES; SOUTHERN SOUTH-AMERICA; GENUS HYSTEROGRAPHIUM; MULTIPLE ALIGNMENT; FUNGI; ASCOMYCOTA; NUCLEAR; EVOLUTION; TAXONOMY AB A reappraisal of the phylogenetic integrity of bitunicate ascomycete fungi belonging to or previously affiliated with the Hysteriaceae, Mytilinidiaceae, Gloniaceae and Patellariaceae is presented, based on an analysis of 121 isolates and four nuclear genes, the ribosomal large and small subunits, transcription elongation factor I and the second largest RNA polymerase 11 subunit. A geographically diverse and high density taxon sampling strategy was employed, including multiple isolates/species from the following genera: Anteaglonium (6/4), Encephalographa (1/1), Farlowiella (3/1), Gloniopsis (8/4), Glonium (4/2), Hysterium (12/5), Hysterabrevium (14/3), Hysterographium (2/1), Hysteropatella (2/2), Lophium (4/2), Mytilinidion (13/10), Oedohysterium (5/3), Ostreichnion (212), Patellaria (1/1), Psiloglonium (11/3), Quasiconcha (1/1), Rhytidhysteron (8/3), and 24 outgroup taxa. Sequence data indicate that although the Hysteriales are closely related to the Pleosporales, sufficient branch support exists for their separation into separate orders within the Pleosporomycetidae. The Mytilinidiales are more distantly related within the subclass and show a dose association with the Gloniaceae. Although there are examples of concordance between morphological and molecular data, these are few. Molecular data instead support the premise of a large number of convergent evolutionary lineages, which do not correspond to previously held assumptions of synapomorphy relating to spore morphology. Thus, within the Hysteriaceae, the genera Gloniopsis, Glonium, Hysterium and Hysterographium are highly polyphyletic. This necessitated the transfer of two species of Hysterium to Oedohysterium gen. nov (Od. insidens comb. nov. and Od. sinense comb. nov), the description of a new species, Hysterium barrianum sp. nov, and the transfer of two species of Gloniopsis to Hysterobrevium gen. nov. (Hb. smilacis comb. nov. and Hb. constrictum comb. nov). While Hysterographium, with the type Hg. fraxini, is removed from the Hysteriaceae, some of its species remain within the family, transferred here to Oedohysterium (Od. pulchrum comb. nov.), Hysterobrevium (Hb. mori comb. nov) and Gloniopsis (Gp. subrugosa comb. nov.); the latter genus, in addition to the type, Gp. praelonga, with two new species, Gp. arciformis sp. nov. and Gp. kenyensis sp. nov. The genus Glonium is now divided into Anteaglonium (Pleosporales), Glonium (Gloniaceae), and Psiloglonium, (Hysteriaceae). The hysterothecium has evolved convergently no less than five times within the Pleosporomycetidae (e.g., Anteaglonium, Farlowiella, Glonium, Hysterographium and the Hysteriaceae). Similarly, thin-walled mytilinidioid (e.g., Ostreichnion) and patellarioid (e.g., Rhytidhysteron) genera, previously in the Mytilinidiaceae and Patellariaceae, respectively, transferred here to the Hysteriaceae, have also evolved at least twice within the subclass. As such, character states traditionally considered to represent synapomorphies among these fungi, whether they relate to spore septation or the ascomata, in fact, represent symplesiomorphies, and most likely have arisen multiple times through convergent evolutionary processes in response to common selective pressures. C1 [Boehm, E. W. A.] Kean Univ, Dept Biol Sci, Union, NJ 07083 USA. [Mugambi, G. K.] Natl Museums Kenya, Dept Bot, Nairobi 00100, Kenya. [Miller, A. N.] Univ Illinois, Illinois Nat Hist Survey, Champaign, IL USA. [Huhndorf, S. M.] Field Museum, Chicago, IL 60605 USA. [Marincowitz, S.] Univ Pretoria, Forestry & Agr Biotechnol Inst, ZA-0002 Pretoria, South Africa. [Spatafora, J. W.] Oregon State Univ, Dept Bot & Plant Pathol, Corvallis, OR USA. [Schoch, C. L.] NIH, Natl Ctr Biotechnol Informat, Natl Lib Med, GenBank, Bethesda, MD 20892 USA. RP Boehm, EWA (reprint author), Kean Univ, Dept Biol Sci, 1000 Morris Ave, Union, NJ 07083 USA. EM eboehm@kean.edu RI Marincowitz, Seonju/A-9185-2008; Schoch, Conrad/J-4825-2012 FU National Science Foundation (NSF) [DBI 0922603, DEB0515558, DEB-0717476]; Discover Life in America [DLIA 2005-15]; NIH; National Library of Medicine FX The authors wish to thank Alain Gardiennet (Veronnes, France), Gintaras Kantvilas (Tasmanian Herbarium, Hobart, Tasmania), Marieka Gryzenhout (Dept. Microbiology and Plant Pathology, Forestry and Agricultural Biotechnology Institute, University of Pretoria, South Africa), Maria Inez Messuti and Laura Emma Lorenzo (Departamento de Botanica, Centro Regional Universitario Bariloche, Universidad Nacional del Comahue, Quintral, Bariloche, Rio Negro, Argentina), Eunice Nkansah (Kean University, Union, NJ, U.S.A.), and Meredith Blackwell (Dept. Biological Sciences, Louisiana State University, Baton Rouge, Louisiana, U.S.A.) for kindly supplying some of the isolates used in this study (Table 1). The authors wish to thank Walter Gams (Baam, The Netherlands) for the Latin translations, and for his numerous helpful insights into the taxonomic and nomenclatural issues raised by this work. We also wish to acknowledge Scott Redhead (National Mycological Herbarium, Agriculture and Agri-Food Canada, Ottawa, Canada) who provided helpful suggestions on the manuscript prior to submission. E.W.A. Boehm wishes to acknowledge support from the National Science Foundation (NSF) Major Research Instrumentation Grant DBI 0922603. A.N. Miller acknowledges funding from the NSF through a BS&I award (DEB0515558) and from Discover Life in America (DLIA 2005-15). Part of this work was also funded by a grant from NSF (DEB-0717476) to J.W. Spatafora (and C.L. Schoch until 2008). Work performed by C.L. Schoch after 2008 was supported in part by the Intramural Research Program of the NIH, National Library of Medicine. NR 122 TC 42 Z9 44 U1 0 U2 11 PU CENTRAALBUREAU SCHIMMELCULTURE PI UTRECHT PA UPPSALALAAN 8, 3584 CT UTRECHT, NETHERLANDS SN 0166-0616 J9 STUD MYCOL JI Stud. Mycol. PY 2009 IS 64 BP 49 EP 83 DI 10.3114/sim.2009.64.03 PG 35 WC Mycology SC Mycology GA 553KQ UT WOS:000274365900004 ER PT J AU Zhang, Y Schoch, CL Fournier, J Crous, PW de Gruyter, J Woudenberg, JHC Hirayama, K Tanaka, K Pointing, SB Spatafora, JW Hyde, KD AF Zhang, Y. Schoch, C. L. Fournier, J. Crous, P. W. de Gruyter, J. Woudenberg, J. H. C. Hirayama, K. Tanaka, K. Pointing, S. B. Spatafora, J. W. Hyde, K. D. TI Multi-locus phylogeny of Pleosporales: a taxonomic, ecological and evolutionary re-evaluation SO STUDIES IN MYCOLOGY LA English DT Review DE Environmental habit; evolution; molecular phylogeny; nutritional mode; taxonomy ID RIBOSOMAL DNA-SEQUENCES; STAGONOSPORA-NODORUM; MOLECULAR PHYLOGENY; LEPTOSPHAERIA-MACULANS; PHAEOSPHAERIA-NODORUM; MULTIGENE PHYLOGENY; MULTIPLE ALIGNMENT; ENDOPHYTIC FUNGI; SP-NOV; ASCOMYCOTA AB Five loci, nucSSU, nucLSU rDNA, TEF1, RPB1 and RPB2, are used for analysing 129 pleosporalean taxa representing 59 genera and 15 families in the current classification of Pleosporales. The suborder Pleosporineae is emended to include four families, viz. Didymellaceae, Leptosphaeriaceae, Phaeosphaeriaceae and Pleosporaceae. In addition, two new families are introduced, i.e. Amniculicolaceae and Lentitheciaceae. Pleomassariaceae is treated as a synonym of Melanommataceae, and new circumscriptions of Lophiostomataceae s. str, Massarinaceae and Lophiotrema are proposed. Familial positions of Entodesmium and Setomelanomma in Phaeosphaeriaceae, Neophaeosphaeria in Leptosphaeriaceae, Leptosphaerulina, Macroventuria and Platychora in Didymellaceae, Pleomassaria in Melanommataceae and Bimuria, Didymocrea, Karstenula and Paraphaeosphaeria in Montagnulaceae are clarified. Both ecological and morphological characters show varying degrees of phylogenetic significance. Pleosporales is most likely derived from a saprobic ancestor with fissitunicate asci containing conspicuous ocular chambers and apical rings. Nutritional shifts in Pleosporales likely occured from saprotrophic to hemibiotrophic or biotrophic. C1 [Hyde, K. D.] Mae Fah Luang Univ, Sch Sci, Muang 57100, Chiang Rai, Thailand. [Zhang, Y.; Pointing, S. B.] Univ Hong Kong, Sch Biol Sci, Div Microbiol, Hong Kong, Hong Kong, Peoples R China. [Schoch, C. L.] NIH, Natl Ctr Biotechnol Informat, Natl Lib Med, Bethesda, MD 20892 USA. [Crous, P. W.; de Gruyter, J.; Woudenberg, J. H. C.] CBS KNAW Fungal Biodivers Ctr, NL-3508 AD Utrecht, Netherlands. [Fournier, J.] Las Muros, F-09420 Rimont, Ariege, France. [de Gruyter, J.] Plant Protect Serv, NL-6700 HC Wageningen, Netherlands. [Hirayama, K.; Tanaka, K.] Hirosaki Univ, Fac Agr & Life Sci, Aomori 0368561, Japan. [Spatafora, J. W.] Oregon State Univ, Dept Bot & Plant Pathol, Corvallis, OR USA. [Hyde, K. D.] Chinese Acad Forestry, Res Inst Resource Insects, Int Fungal Res & Dev Ctr, Kunming 650034, Yunnan, Peoples R China. RP Hyde, KD (reprint author), Mae Fah Luang Univ, Sch Sci, Muang 57100, Chiang Rai, Thailand. EM kdhyde2@gmail.com RI Crous, Pedro/H-1489-2012; Schoch, Conrad/J-4825-2012; Woudenberg, Joyce H.C./C-9384-2013; Tanaka, Kazuaki/F-1924-2013 OI Crous, Pedro/0000-0001-9085-8825; Woudenberg, Joyce H.C./0000-0002-7337-6864; FU NIH; National Library of Medicine; NSF [DEB 0717476] FX The authors thank O.E. Eriksson for his comments on a draft version of this script, as well as two other anonymous reviewers. Dr Shaun Pennycook is thanked for his valuable suggestions on nomenclature. The University of Hong Kong is thanked for providing YZ with a postgraduate studentship. Work performed by CLS after 2008 was supported in part by the Intramural Research Program of the NIH, National Library of Medicine. This work was funded by a grant from NSF to JWS and to CLS until 2008 (DEB 0717476). NR 151 TC 141 Z9 144 U1 1 U2 34 PU CENTRAALBUREAU SCHIMMELCULTURE PI UTRECHT PA UPPSALALAAN 8, 3584 CT UTRECHT, NETHERLANDS SN 0166-0616 J9 STUD MYCOL JI Stud. Mycol. PY 2009 IS 64 BP 85 EP 102 DI 10.3114/sim.2009.64.04 PG 18 WC Mycology SC Mycology GA 553KQ UT WOS:000274365900005 PM 20169024 ER PT J AU Ruibal, C Gueidan, C Selbmann, L Gorbushina, AA Crous, PW Groenewald, JZ Muggia, L Grube, M Isola, D Schoch, CL Staley, JT Lutzoni, F de Hoog, GS AF Ruibal, C. Gueidan, C. Selbmann, L. Gorbushina, A. A. Crous, P. W. Groenewald, J. Z. Muggia, L. Grube, M. Isola, D. Schoch, C. L. Staley, J. T. Lutzoni, F. de Hoog, G. S. TI Phylogeny of rock-inhabiting fungi related to Dothideomycetes SO STUDIES IN MYCOLOGY LA English DT Article DE Arthoniomycetes; Capnodiales; Dothideomycetes; evolution; extremotolerance; multigene phylogeny; rock-inhabiting fungi ID SUBUNIT RIBOSOMAL DNA; MICROCOLONIAL FUNGI; MERISTEMATIC FUNGI; LICHENIZED FUNGI; ANTIQUE MARBLES; BLACK YEASTS; PCR PRIMERS; EVOLUTION; ASCOMYCOTA; LIFE AB The class Dothideomycetes (along with Eurotiomycetes) includes numerous rock-inhabiting fungi (RIF), a group of ascomycetes that tolerates surprisingly well harsh conditions prevailing on rock surfaces. Despite their convergent morphology and physiology, RIF are phylogenetically highly diverse in Dothideomycetes. However, the positions of main groups of RIF in this Class remain unclear due to the lack of a strong phylogenetic framework. Moreover, connections between rock-dwelling habit and other lifestyles found in Dothideomycetes such as plant pathogens, saprobes and lichen-forming fungi are still unexplored. Based on multigene phylogenetic analyses, we report that RIF belong to Capnodiales (particularly to the family Teratosphaeriaceae s.l.), Dothideales, Pleosporales, and Myriangiales, as well as some uncharacterised groups with affinities to Dothideomycetes. Moreover, one lineage consisting exclusively of RIF proved to be closely related to Arthoniomycetes, the sister class of Dothideomycetes. The broad phylogenetic amplitude of RIF in Dothideomycetes suggests that total species richness in this class remains underestimated. Composition of some RIF-rich lineages suggests that rock surfaces are reservoirs for plant-associated fungi or saprobes, although other data also agree with rocks as a primary substrate for ancient fungal lineages. According to the current sampling, long distance dispersal seems to be common for RIF. Dothideomycetes lineages comprising lichens also include RIF, suggesting a possible link between rock-dwelling habit and lichenisation. C1 [Ruibal, C.] Univ Politecn Madrid, Escuela Tecn Super Ingenieros Ind, Dept Ingn & Ciencia Mat, E-28006 Madrid, Spain. [Gueidan, C.; Crous, P. W.; Groenewald, J. Z.; de Hoog, G. S.] CBS KNAW Fungal Biodivers Ctr, NL-3508 AD Utrecht, Netherlands. [Selbmann, L.; Isola, D.] Largo Univ, Univ Tuscia, DECOS, Viterbo, Italy. [Gorbushina, A. A.] Free Univ Berlin, D-12205 Berlin, Germany. [Gorbushina, A. A.] BAM Fed Inst Mat Res & Testing, Dept Mat & Environm 4, D-12205 Berlin, Germany. [Muggia, L.; Grube, M.] Karl Franzens Univ Graz, Inst Pflanzenwissensch, A-8010 Graz, Austria. [Schoch, C. L.] NIH, NCBI, Natl Lib Med, Bethesda, MD 20892 USA. [Staley, J. T.] Univ Washington, Dept Microbiol, Seattle, WA 98195 USA. [Lutzoni, F.] Duke Univ, Dept Biol, Durham, NC 27708 USA. RP Ruibal, C (reprint author), Univ Politecn Madrid, Escuela Tecn Super Ingenieros Ind, Dept Ingn & Ciencia Mat, Jose Gutierrez Abascal 2, E-28006 Madrid, Spain. EM tinoruibal@yahoo.com RI Groenewald, Johannes/F-4667-2011; Crous, Pedro/H-1489-2012; Schoch, Conrad/J-4825-2012; Selbmann, Laura/L-3056-2013; Gueidan, Cecile/C-8803-2014; OI Crous, Pedro/0000-0001-9085-8825; Ruibal Villasenor, Constantino/0000-0003-3494-7051; Grube, Martin/0000-0001-6940-5282 FU NSF AToL [DEB-0228725, DEB-0717476]; National Institutes of Health (National Library of Medicine); National Swiss Foundation [31003A-122513]; Deutsche Forschungsgerneinschaft [Go 897/3]; Synthesys grant FX Work performed by C.R. at Duke University was supported by a NSF AToL grant (AFTOL, DEB-0228725) to F.L. Work performed by C.L.S. after 2008 was supported in part by the Intramural Research Program of the National Institutes of Health (National Library of Medicine), and until 2008 by a grant from NSF (DEB-0717476). Work performed by A.A.G. was funded by grants from the National Swiss Foundation (31003A-122513) and the Deutsche Forschungsgerneinschaft (DFG Go 897/3). Work performed by L.S. at the CBS was funded by a Synthesys grant. The authors would like to acknowledge the Italian National Program for Antarctic Research (PNRA) for supporting the collection of samples, the Italian National Antarctic Museum 'Felice Ippolito" for supporting the Culture Collection of Fungi' From Extreme Environments (CCFEE) and the Alpine guides A. Serafini and M. Heltai for collecting rock samples in the Alps and Aconcagua, respectively. Thanks to William Broughton for his editorial help and to the technical staff of the CBS for their assistance with the cultures. NR 85 TC 66 Z9 68 U1 2 U2 13 PU CENTRAALBUREAU SCHIMMELCULTURE PI UTRECHT PA PO BOX 85167, 3508 AD UTRECHT, NETHERLANDS SN 0166-0616 EI 1872-9797 J9 STUD MYCOL JI Stud. Mycol. PY 2009 IS 64 BP 123 EP 133 DI 10.3114/sim.2009.64.06 PG 11 WC Mycology SC Mycology GA 553KQ UT WOS:000274365900007 ER PT J AU Suetrong, S Schoch, CL Spatafora, JW Kohlmeyer, J Volkmann-Kohlmeyer, B Sakayaroj, J Phongpaichit, S Tanaka, K Hirayama, K Jones, EBG AF Suetrong, S. Schoch, C. L. Spatafora, J. W. Kohlmeyer, J. Volkmann-Kohlmeyer, B. Sakayaroj, J. Phongpaichit, S. Tanaka, K. Hirayama, K. Jones, E. B. G. TI Molecular systematics of the marine Dothideomycetes SO STUDIES IN MYCOLOGY LA English DT Review DE Dothideomycetes; ecology; marine fungi; multi-locus; new genera; systematics ID MULTIPLE SEQUENCE ALIGNMENT; INTERTIDAL MANGROVE WOOD; RIBOSOMAL DNA-SEQUENCES; MORPHOLOGICALLY SIMILAR GENERA; SP-NOV; PHYLOGENETIC-RELATIONSHIPS; JUNCUS-ROEMERIANUS; FRESH-WATER; RDNA SEQUENCES; NYPA-FRUTICANS AB Phylogenetic analyses of four nuclear genes, namely the large and small subunits of the nuclear ribosomal RNA, transcription elongation factor I-alpha and the second largest RNA polymerase 11 subunit, established that the ecological group of marine bitunicate ascomycetes has representatives in the orders Capnodiales, Hysteriales, Jahnulales, Mytilinidiales, Patellariales and Pleosporales. Most of the fungi sequenced were intertidal mangrove taxa and belong to members of 12 families in the Pleosporales: Aigialaceae, Didymellaceae, Leptosphaeriaceae, Lenthitheciaceae, Lophiostomataceae, Massarinaceae, Montagnulaceae, Morosphaeriaceae, Phaeosphaeriaceae, Pleosporaceae, Testudinaceae and Trematosphaeriaceae. Two new families are described: Aigialaceae and Morosphaeriaceae, and three new genera proposed: Halomassarina, Morosphaerial and Rimora. Few marine species are reported from the Dothideomycetidae (e.g. Mycosphaerellaceae, Capnodiales), a group poorly studied at the molecular level. New marine lineages include the Testudinaceae and Manglicola guatemalensis in the Jahnulales. Significantly, most marine Dothideomycetes are intertidal tropical species with only a few from temperate regions on salt marsh plants (Spartina species and Juncus roemerianus), and rarely totally submerged (e.g. Halotthia posidoniae and Pontoporeia biturbinata on the seagrasses Posidonia oceanica and Cymodocea nodosum). Specific attention is given to the adaptation of the Dothideomycetes to the marine milieu, new lineages of marine fungi and their host specificity. C1 [Suetrong, S.; Sakayaroj, J.; Jones, E. B. G.] Natl Ctr Genet Engn & Biotechnol BIOTEC, Bioresources Technol Unit, Khlong Luang 12120, Pathum Thani, Thailand. [Suetrong, S.; Phongpaichit, S.] Prince Songkla Univ, Fac Sci, Dept Microbiol, Hat Yai 90112, Songkhla, Thailand. [Schoch, C. L.] NIH, Natl Ctr Biothechnol Informat, Natl Lib Med, Bethesda, MD 20892 USA. [Spatafora, J. W.] Oregon State Univ, Dept Bot & Plant Pathol, Corvallis, OR 97331 USA. [Kohlmeyer, J.; Volkmann-Kohlmeyer, B.] Univ N Carolina Chapel Hill, Inst Marine Sci, Morehead City, NC 28557 USA. [Tanaka, K.; Hirayama, K.] Hirosaki Univ, Fac Agr & Life Sci, Aomori 0368561, Japan. RP Jones, EBG (reprint author), Natl Ctr Genet Engn & Biotechnol BIOTEC, Bioresources Technol Unit, 113 Thailand Sci Pk,Paholyothin Rd,Khlong 1, Khlong Luang 12120, Pathum Thani, Thailand. EM remispora@gmail.com RI Sakayaroj, Jariya/D-1845-2012; Schoch, Conrad/J-4825-2012; Jones, Gareth/C-5137-2013; Tanaka, Kazuaki/F-1924-2013 FU TRF/BIOTEC Special Program for Biodiversity Research and Training [BRT R251006, BRT R351004, BRT R352015]; TOTAL Corporate Foundation; TOTAL E P Thailand; Prince of Songkla University; NIH; National Library of Medicine; NSF [DEB-0717476] FX This work was supported by TRF/BIOTEC Special Program for Biodiversity Research and Training Grant BRT R251006, BRT R351004 BRT R352015, and a TOTAL Corporate Foundation, TOTAL E & P Thailand. We thank Y. Zhang and Dr K.D. Hyde for exchange of data and useful discussions. SS acknowledges the Songklanagarind Scholarship for Graduate Studies from the Prince of Songkla University. We thank Prof. M. Tanticharoen, Dr K. Kirtikara and Dr L. Eurwilaichitr for continued support. We thank A. Klaysuban for technical assistance, and U. Pinruan, N. Rungjindamai, R. Choeyklin, A. Loilong, S. Preedanon and O. Supaphon for assistance with the field work. Work performed by CLS after 2008 was supported in part by the Intramural Research Program of the NIH, National Library of Medicine. Part of this work was also funded by a grant from NSF (DEB-0717476) to JWS and CLS (until 2008). NR 175 TC 88 Z9 91 U1 10 U2 23 PU CENTRAALBUREAU SCHIMMELCULTURE PI UTRECHT PA UPPSALALAAN 8, 3584 CT UTRECHT, NETHERLANDS SN 0166-0616 J9 STUD MYCOL JI Stud. Mycol. PY 2009 IS 64 BP 155 EP 173 DI 10.3114/sim.2009.64.09 PG 19 WC Mycology SC Mycology GA 553KQ UT WOS:000274365900010 ER PT J AU Phillips, KA Chaudhry, A Nahvi, S Kunins, H Gourevitch, M Alford, DP AF Phillips, K. A. Chaudhry, A. Nahvi, S. Kunins, H. Gourevitch, M. Alford, D. P. TI Impact of an Office-Based Opioid Treatment (OBOT) Workshop SO SUBSTANCE ABUSE LA English DT Meeting Abstract C1 [Phillips, K. A.] NIDA, Bethesda, MD USA. [Chaudhry, A.] Johns Hopkins Univ, Sch Med, Baltimore, MD 21218 USA. [Nahvi, S.; Kunins, H.] Albert Einstein Coll Med, Bronx, NY USA. [Gourevitch, M.] NYU, Sch Med, New York, NY 10003 USA. [Alford, D. P.] Boston Univ, Sch Med, Boston, MA 02215 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ROUTLEDGE JOURNALS, TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXFORDSHIRE, ENGLAND SN 0889-7077 J9 SUBST ABUS JI Subst. Abus. PY 2009 VL 30 IS 1 BP 92 EP 93 PG 2 WC Substance Abuse SC Substance Abuse GA 668WO UT WOS:000283304800030 ER PT J AU Phillips, KA Walley, AY Gordon, AJ AF Phillips, K. A. Walley, A. Y. Gordon, A. J. TI Patients in Recovery (PIR): Success at Teaching Opioid Addiction Treatments to Physicians SO SUBSTANCE ABUSE LA English DT Meeting Abstract C1 [Phillips, K. A.] NIDA, NIH, Bethesda, MD USA. [Walley, A. Y.] Boston Univ, Sch Med, Boston, MA 02215 USA. [Gordon, A. J.] Univ Pittsburgh, Sch Med, Pittsburgh, PA 15260 USA. NR 0 TC 0 Z9 0 U1 0 U2 3 PU ROUTLEDGE JOURNALS, TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXFORDSHIRE, ENGLAND SN 0889-7077 J9 SUBST ABUS JI Subst. Abus. PY 2009 VL 30 IS 1 BP 96 EP 97 PG 2 WC Substance Abuse SC Substance Abuse GA 668WO UT WOS:000283304800037 ER PT J AU Hermos, J Winter, M Heeren, T Hingson, R AF Hermos, J. Winter, M. Heeren, T. Hingson, R. TI Alcohol-Related Problems Among Younger Drinkers Who Misuse Prescription Drugs: Results from the National Epidemiologic Survey of Alcohol and Related Conditions (NESARC) SO SUBSTANCE ABUSE LA English DT Article DE Alcohol-related problems; prescription drug misuse; young drinkers ID DSM-IV ALCOHOL; AGE-OF-ONSET; USE DISORDERS; SUBSTANCE USE; NATURAL-HISTORY; NONMEDICAL USE; UNITED-STATES; PREVALENCE; DRINKING; COOCCURRENCE AB The authors determined whether lifetime prescription drug misuse ( PDM) associated with increased risks for alcohol-related problems among 18- to 34-year-old, NESARC respondents. Among 8222 "ever-drinkers," 15.4% reported ever "misusing sedatives, tranquilizers, painkillers or stimulants ... as prescriptions or from indirect sources." Outcomes were within two alcohol-related problem domains, "risk-taking behaviors," including driving while drinking, fights, injuries, and arrests, and "interpersonal troubles," including problems with jobs, family, or friends. Among all drinkers and among alcohol-dependent and cannabis-using subsamples, those reporting PDM were significantly more likely to report alcohol-related "risk-taking behaviors" or "interpersonal troubles" than were those without PDM. In adjusted analysis, young age drinking onsets, and heavy and dependent drinking independently increased these risks. Results of this cross-sectional analysis support the need for longitudinal data to more clearly define the association between drinking problems and PDM, and which can support prevention, treatment, and harm-reduction efforts for younger, multisubstance users. C1 [Hermos, J.; Winter, M.; Heeren, T.; Hingson, R.] Boston Univ, Sch Publ Hlth, Youth Alcohol Prevent Ctr, Boston, MA USA. [Hermos, J.; Hingson, R.] Boston Univ, Sch Publ Hlth, Dept Social & Behav Sci, Boston, MA USA. [Winter, M.; Heeren, T.] Boston Univ, Sch Publ Hlth, Dept Biostat, Boston, MA USA. [Hingson, R.] NIAAA, Div Epidemiol & Prevent, NIH, Bethesda, MD USA. RP Hermos, J (reprint author), VA Boston Healthcare Syst 151MAV, 150 S Huntington Ave, Boston, MA 02130 USA. EM jhermos@bu.edu OI Heeren, Timothy/0000-0001-5643-3559 FU National Institute on Alcohol Abuse and Alcoholism for the Youth Alcohol Prevention Center, Boston University School of Public Health; Statistical Coordinating Center, Boston University School of Public Health FX This work was supported by Core Funds from the National Institute on Alcohol Abuse and Alcoholism for the Youth Alcohol Prevention Center, Boston University School of Public Health, and Core Funds from the Statistical Coordinating Center, Boston University School of Public Health. NR 22 TC 9 Z9 9 U1 2 U2 5 PU ROUTLEDGE JOURNALS, TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXFORDSHIRE, ENGLAND SN 0889-7077 J9 SUBST ABUS JI Subst. Abus. PY 2009 VL 30 IS 2 BP 118 EP 126 DI 10.1080/08897070902802034 PG 9 WC Substance Abuse SC Substance Abuse GA 668WZ UT WOS:000283306600002 PM 19347751 ER PT B AU Mukhopadhyay, D Dasso, M AF Mukhopadhyay, Debaditya Dasso, Mary BE Wilson, VG TI The SUMO Pathway in Mitosis SO SUMO REGULATION OF CELLULAR PROCESSES LA English DT Article; Book Chapter DE Mitosis; SUMO; Condensin; Topoisomerase; Kinetochore ID SEPTIN-INTERACTING PROTEINS; DNA TOPOISOMERASE-II; E3 LIGASE ACTIVITY; SACCHAROMYCES-CEREVISIAE; CENP-E; IN-VIVO; CHROMOSOME SEGREGATION; SUMOYLATED PROTEINS; CENTROMERE PROTEIN; SISTER CHROMATIDS AB Mitosis is the stage of the cell cycle during which replicated chromosomes must be precisely divided to allow the formation of two daughter cells possessing equal genetic material. Much of the careful spatial and temporal organization of mitosis is maintained through post-translational modifications, such as phosphorylation and ubiquitination, of key cellular proteins. Here, we will review evidence that sumoylation, conjugation to the SUMO family of small ubiquitin-like modifiers, also serves essential regulatory roles during mitosis. We will discuss the basic biology of sumoylation, how the SUMO pathway has been implicated in particular mitotic functions, including chromosome condensation, centromere/kinetochore organization and cytokinesis, and what cellular proteins may be the targets underlying these phenomena. C1 [Mukhopadhyay, Debaditya; Dasso, Mary] Natl Inst Child Hlth & Dev, Sect Cell Cycle Regulat, Lab Gene Regulat & Dev, NIH, Bethesda, MD 20892 USA. RP Dasso, M (reprint author), Natl Inst Child Hlth & Dev, Sect Cell Cycle Regulat, Lab Gene Regulat & Dev, NIH, Bethesda, MD 20892 USA. EM mukhopad@mail.nih.gov; mdasso@helix.nih.gov OI Dasso, Mary/0000-0002-5410-1371 NR 96 TC 1 Z9 1 U1 0 U2 3 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013, UNITED STATES BN 978-90-481-2648-4 PY 2009 BP 153 EP 169 DI 10.1007/978-90-481-2649-1_9 D2 10.1007/978-90-481-2649-1 PG 17 WC Cell Biology; Medicine, Research & Experimental SC Cell Biology; Research & Experimental Medicine GA BNH44 UT WOS:000274564200009 ER PT J AU Atlas, RM AF Atlas, Ronald M. GP Natl Res Council TI A SURVEY OF ATTITUDES AND ACTIONS ON DUAL USE RESEARCH IN THE LIFE SCIENCES A Collaborative Effort of the National Research Council and the American Association for the Advancement of Science Summary SO SURVEY OF ATTITUDES AND ACTIONS ON DUAL USE RESEARCH IN THE LIFE SCIENCES: A COLLABORATIVE EFFORT OF THE NATIONAL RESEARCH COUNCIL AND THE AMERICAN ASSOCIATION FOR THE ADVANCEMENT OF SCIENCE LA English DT Editorial Material; Book Chapter ID BIOLOGICAL WEAPONS; ETHICAL-ISSUES; SCIENTIFIC-RESEARCH; RESEARCH NORMS; 1918 FLU; VIRUS; GENETICS; CODES; INDUSTRY; FACULTY C1 [Atlas, Ronald M.] Univ Louisville, Biol & Publ Hlth, Louisville, KY 40292 USA. [Atlas, Ronald M.] Univ Louisville, Ctr Hlth Hazards Preparedness, Louisville, KY 40292 USA. [Atlas, Ronald M.] NASA, Planetary Protect Board, Washington, DC USA. [Atlas, Ronald M.] Wellcome Trust Infect Immunol & Populat Hlth Stra, Baltimore, MD USA. [Atlas, Ronald M.] ASM Task Force Biodef, Boston, MA USA. [Atlas, Ronald M.] ASM, Madison, WI USA. [Atlas, Ronald M.] NIH, Recombinant DNA Advisory Comm, Baltimore, MD USA. [Atlas, Ronald M.] Dept Homeland Secur Sci & Technol Advisory Comm, Oslo, Norway. [Atlas, Ronald M.] Fed Bur Invest Sci Working Grp Bioforens, London, England. RP Atlas, RM (reprint author), Univ Louisville, Biol & Publ Hlth, Louisville, KY 40292 USA. NR 168 TC 1 Z9 1 U1 1 U2 1 PU NATL ACADEMIES PRESS PI WASHINGTON PA 2101 CONSTITUTION AVE, WASHINGTON, DC 20418 USA BN 978-0-309-12510-9 PY 2009 BP 1 EP + PG 20 WC Education & Educational Research SC Education & Educational Research GA BC4IZ UT WOS:000352554100002 ER PT J AU Atlas, RM AF Atlas, Ronald M. GP Natl Res Council TI A SURVEY OF ATTITUDES AND ACTIONS ON DUAL USE RESEARCH IN THE LIFE SCIENCES A Collaborative Effort of the National Research Council and the American Association for the Advancement of Science Preface and Acknowledgments SO SURVEY OF ATTITUDES AND ACTIONS ON DUAL USE RESEARCH IN THE LIFE SCIENCES: A COLLABORATIVE EFFORT OF THE NATIONAL RESEARCH COUNCIL AND THE AMERICAN ASSOCIATION FOR THE ADVANCEMENT OF SCIENCE LA English DT Editorial Material; Book Chapter C1 [Atlas, Ronald M.] Univ Louisville, Biol & Publ Hlth, Louisville, KY 40292 USA. [Atlas, Ronald M.] Univ Louisville, Ctr Hlth Hazards Preparedness, Louisville, KY 40292 USA. [Atlas, Ronald M.] NASA, Planetary Protect Board, Washington, DC USA. [Atlas, Ronald M.] Wellcome Trust Infect Immunol & Populat Hlth Stra, Baltimore, MD USA. [Atlas, Ronald M.] ASM Task Force Biodef, Boston, MA USA. [Atlas, Ronald M.] ASM, Madison, WI USA. [Atlas, Ronald M.] NIH, Recombinant DNA Advisory Comm, Baltimore, MD USA. [Atlas, Ronald M.] Dept Homeland Secur Sci & Technol Advisory Comm, Oslo, Norway. [Atlas, Ronald M.] Fed Bur Invest Sci Working Grp Bioforens, London, England. RP Atlas, RM (reprint author), Univ Louisville, Biol & Publ Hlth, Louisville, KY 40292 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATL ACADEMIES PRESS PI WASHINGTON PA 2101 CONSTITUTION AVE, WASHINGTON, DC 20418 USA BN 978-0-309-12510-9 PY 2009 BP VII EP IX PG 3 WC Education & Educational Research SC Education & Educational Research GA BC4IZ UT WOS:000352554100001 ER PT J AU Atlas, RM AF Atlas, Ronald M. GP Natl Res Council TI A SURVEY OF ATTITUDES AND ACTIONS ON DUAL USE RESEARCH IN THE LIFE SCIENCES A Collaborative Effort of the National Research Council and the American Association for the Advancement of Science Overview SO SURVEY OF ATTITUDES AND ACTIONS ON DUAL USE RESEARCH IN THE LIFE SCIENCES: A COLLABORATIVE EFFORT OF THE NATIONAL RESEARCH COUNCIL AND THE AMERICAN ASSOCIATION FOR THE ADVANCEMENT OF SCIENCE LA English DT Editorial Material; Book Chapter C1 [Atlas, Ronald M.] Univ Louisville, Biol & Publ Hlth, Louisville, KY 40292 USA. [Atlas, Ronald M.] Univ Louisville, Ctr Hlth Hazards Preparedness, Louisville, KY 40292 USA. [Atlas, Ronald M.] NASA, Planetary Protect Board, Washington, DC USA. [Atlas, Ronald M.] Wellcome Trust Infect Immunol & Populat Hlth Stra, Baltimore, MD USA. [Atlas, Ronald M.] ASM Task Force Biodef, Boston, MA USA. [Atlas, Ronald M.] ASM, Madison, WI USA. [Atlas, Ronald M.] NIH, Recombinant DNA Advisory Comm, Baltimore, MD USA. [Atlas, Ronald M.] Dept Homeland Secur Sci & Technol Advisory Comm, Oslo, Norway. [Atlas, Ronald M.] Fed Bur Invest Sci Working Grp Bioforens, London, England. RP Atlas, RM (reprint author), Univ Louisville, Biol & Publ Hlth, Louisville, KY 40292 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATL ACADEMIES PRESS PI WASHINGTON PA 2101 CONSTITUTION AVE, WASHINGTON, DC 20418 USA BN 978-0-309-12510-9 PY 2009 BP 11 EP 41 PG 31 WC Education & Educational Research SC Education & Educational Research GA BC4IZ UT WOS:000352554100003 ER PT J AU Atlas, RM AF Atlas, Ronald M. GP Natl Res Council TI Approach SO SURVEY OF ATTITUDES AND ACTIONS ON DUAL USE RESEARCH IN THE LIFE SCIENCES: A COLLABORATIVE EFFORT OF THE NATIONAL RESEARCH COUNCIL AND THE AMERICAN ASSOCIATION FOR THE ADVANCEMENT OF SCIENCE LA English DT Article; Book Chapter C1 [Atlas, Ronald M.] Univ Louisville, Biol & Publ Hlth, Louisville, KY 40292 USA. [Atlas, Ronald M.] Univ Louisville, Ctr Hlth Hazards Preparedness, Louisville, KY 40292 USA. [Atlas, Ronald M.] NASA, Planetary Protect Board, Washington, DC USA. [Atlas, Ronald M.] Wellcome Trust Infect Immunol & Populat Hlth Stra, Baltimore, MD USA. [Atlas, Ronald M.] ASM Task Force Biodef, Boston, MA USA. [Atlas, Ronald M.] ASM, Madison, WI USA. [Atlas, Ronald M.] NIH, Recombinant DNA Advisory Comm, Baltimore, MD USA. [Atlas, Ronald M.] Dept Homeland Secur Sci & Technol Advisory Comm, Oslo, Norway. [Atlas, Ronald M.] Fed Bur Invest Sci Working Grp Bioforens, London, England. RP Atlas, RM (reprint author), Univ Louisville, Biol & Publ Hlth, Louisville, KY 40292 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATL ACADEMIES PRESS PI WASHINGTON PA 2101 CONSTITUTION AVE, WASHINGTON, DC 20418 USA BN 978-0-309-12510-9 PY 2009 BP 43 EP 61 PG 19 WC Education & Educational Research SC Education & Educational Research GA BC4IZ UT WOS:000352554100004 ER PT J AU Atlas, RM AF Atlas, Ronald M. GP Natl Res Council TI Results of the Survey SO SURVEY OF ATTITUDES AND ACTIONS ON DUAL USE RESEARCH IN THE LIFE SCIENCES: A COLLABORATIVE EFFORT OF THE NATIONAL RESEARCH COUNCIL AND THE AMERICAN ASSOCIATION FOR THE ADVANCEMENT OF SCIENCE LA English DT Article; Book Chapter C1 [Atlas, Ronald M.] Univ Louisville, Biol & Publ Hlth, Louisville, KY 40292 USA. [Atlas, Ronald M.] Univ Louisville, Ctr Hlth Hazards Preparedness, Louisville, KY 40292 USA. [Atlas, Ronald M.] NASA, Planetary Protect Board, Washington, DC USA. [Atlas, Ronald M.] Wellcome Trust Infect Immunol & Populat Hlth Stra, Baltimore, MD USA. [Atlas, Ronald M.] ASM Task Force Biodef, Boston, MA USA. [Atlas, Ronald M.] ASM, Madison, WI USA. [Atlas, Ronald M.] NIH, Recombinant DNA Advisory Comm, Baltimore, MD USA. [Atlas, Ronald M.] Dept Homeland Secur Sci & Technol Advisory Comm, Oslo, Norway. [Atlas, Ronald M.] Fed Bur Invest Sci Working Grp Bioforens, London, England. RP Atlas, RM (reprint author), Univ Louisville, Biol & Publ Hlth, Louisville, KY 40292 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATL ACADEMIES PRESS PI WASHINGTON PA 2101 CONSTITUTION AVE, WASHINGTON, DC 20418 USA BN 978-0-309-12510-9 PY 2009 BP 63 EP 113 PG 51 WC Education & Educational Research SC Education & Educational Research GA BC4IZ UT WOS:000352554100005 ER PT J AU Atlas, RM AF Atlas, Ronald M. GP Natl Res Council TI A SURVEY OF ATTITUDES AND ACTIONS ON DUAL USE RESEARCH IN THE LIFE SCIENCES A Collaborative Effort of the National Research Council and the American Association for the Advancement of Science Conclusions and Recommendations SO SURVEY OF ATTITUDES AND ACTIONS ON DUAL USE RESEARCH IN THE LIFE SCIENCES: A COLLABORATIVE EFFORT OF THE NATIONAL RESEARCH COUNCIL AND THE AMERICAN ASSOCIATION FOR THE ADVANCEMENT OF SCIENCE LA English DT Editorial Material; Book Chapter C1 [Atlas, Ronald M.] Univ Louisville, Biol & Publ Hlth, Louisville, KY 40292 USA. [Atlas, Ronald M.] Univ Louisville, Ctr Hlth Hazards Preparedness, Louisville, KY 40292 USA. [Atlas, Ronald M.] NASA, Planetary Protect Board, Washington, DC USA. [Atlas, Ronald M.] Wellcome Trust Infect Immunol & Populat Hlth Stra, Baltimore, MD USA. [Atlas, Ronald M.] ASM Task Force Biodef, Boston, MA USA. [Atlas, Ronald M.] ASM, Madison, WI USA. [Atlas, Ronald M.] NIH, Recombinant DNA Advisory Comm, Baltimore, MD USA. [Atlas, Ronald M.] Dept Homeland Secur Sci & Technol Advisory Comm, Oslo, Norway. [Atlas, Ronald M.] Fed Bur Invest Sci Working Grp Bioforens, London, England. RP Atlas, RM (reprint author), Univ Louisville, Biol & Publ Hlth, Louisville, KY 40292 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATL ACADEMIES PRESS PI WASHINGTON PA 2101 CONSTITUTION AVE, WASHINGTON, DC 20418 USA BN 978-0-309-12510-9 PY 2009 BP 115 EP 122 PG 8 WC Education & Educational Research SC Education & Educational Research GA BC4IZ UT WOS:000352554100006 ER PT J AU Finnema, SJ Donohue, SR Zoghbi, SS Brown, AK Gulyas, B Innis, RB Halldin, C Pike, VW AF Finnema, Sjoerd J. Donohue, Sean R. Zoghbi, Sami S. Brown, Amira K. Gulyas, Balazs Innis, Robert B. Halldin, Christer Pike, Victor W. TI Evaluation of [C-11]PipISB and [F-18]PipISB in Monkey as Candidate Radioligands for Imaging Brain Cannabinoid Type-1 Receptors In Vivo SO SYNAPSE LA English DT Article DE positron emission tomography; carbon-11; fluorine-18; radiotracer ID INVERSE AGONIST; RAT-BRAIN; DRUG DEVELOPMENT; PET; LOCALIZATION; SR141716A; BINDS; DRONABINOL; ANOREXIA; OBESITY AB N-(4-Fluorobenzyl)-4-[3-(piperidin-1-yl)indole-1-sulfonyl]benzamide] (PipISB, 3) is a selective and high-potency cannabinoid subtype-1 (CBI) receptor inverse agonist. We have previously reported radiosyntheses of [C-11]3 and [F-18]3. Here, we aimed to evaluate the uptake and CB, receptor-specific binding of each radioligand in monkey brain in vivo with positron emission tomography (PET). [C-11]3 or [F-18]3 was injected intravenously into rhesus or cynomolgus monkey, respectively, and examined with PET at baseline or after pretreatment with a receptor-saturating dose of CB1 receptor-selective ligand (3 for [C-11]3 or 8 for [F-18](3)). In one PET experiment, the dose of 3 was administered at 100 min after [C-11]3. Relative plasma concentrations of radioligand and radiometabolites were concurrently measured in baseline experiments with high-performance liquid chromatography. Brain radioactivity uptake was highest in striatum and cerebellum, and it reached 170-270% standardized uptake value (SUV) at 120 min after injection of [C-11](3) and 180% SUV at 240 min after injection of [F-18](3). Radioactivity was well retained in all CBI receptor-rich regions. No reference region could be identified for nonspecifically bound radioligand. Under CB1 receptor pretreatment and displacement conditions, initial brain uptakes of radioactivity were similar to those at baseline. Regional brain radioactivity concentrations then became homogeneous and diminished to between 70 and 80% SUV at 120 min after injection of [C-11]3 and to 25% SUV at 240 min after injection of [F-18]3. [F-18]3 was not defluorinated but was metabolized to less lipophilic radiometabolites, as was [C-11]3. Hence, [C-11]3 and [F-18]3 showed high CBI receptor-specific binding in monkey brain in vivo and merit further investigation as prospective PET radioligands in humans. Synapse 63:22-30, 2009. Published 2008 Wiley-Liss, Inc. C1 [Donohue, Sean R.; Zoghbi, Sami S.; Brown, Amira K.; Innis, Robert B.; Pike, Victor W.] NIMH, Mol Imaging Branch, NIH, Bethesda, MD 20892 USA. [Finnema, Sjoerd J.; Donohue, Sean R.; Gulyas, Balazs; Halldin, Christer] Karolinska Hosp, Karolinska Inst, Dept Clin Neurosci, Psychiat Sect, S-17176 Stockholm, Sweden. RP Pike, VW (reprint author), NIMH, Mol Imaging Branch, NIH, Bldg 10,Rm B3 C346A,10 Ctr Dr, Bethesda, MD 20892 USA. EM pikev@mail.nih.gov RI Gulyas, Balazs/F-9508-2015 FU National Institute of Mental Health [Z01-MH-002795] FX Contract grant sponsor: National Institute of Mental Health; Contract grant number: Z01-MH-002795 NR 39 TC 7 Z9 7 U1 0 U2 1 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0887-4476 J9 SYNAPSE JI Synapse PD JAN PY 2009 VL 63 IS 1 BP 22 EP 30 DI 10.1002/syn.20578 PG 9 WC Neurosciences SC Neurosciences & Neurology GA 383FB UT WOS:000261658400004 PM 18925657 ER PT B AU Galperin, MY AF Galperin, Michael Y. BE Lee, SY TI Sensory Transduction Network of E. coli SO SYSTEMS BIOLOGY AND BIOTECHNOLOGY OF ESCHERICHIA COLI LA English DT Article; Book Chapter ID COMPLETE GENOME SEQUENCE; 2-COMPONENT SIGNAL-TRANSDUCTION; BACTERIAL RESPONSE REGULATORS; C-DI-GMP; ESCHERICHIA-COLI; PROTEIN-PHOSPHORYLATION; CYCLIC DIGUANYLATE; RNA-POLYMERASE; IN-VITRO; DOMAIN AB The genome of Escherichia coli K12 encodes at least 6 classes of sensor proteins: 30 histidine protein kinases, 5 methyl-accepting chemotaxis proteins, 23 membrane components of the sugar: phosphotransferase system (PTS), 29 proteins with diguanylate cyclase and/or c-di-GMP-specific phosphodiesterase activity and two predicted serine/threonine protein kinases. The full signal transduction network additionally includes 32 response regulators, numerous chemotaxis proteins, PTS components, adenylate cyclase, CRP, and uncharacterized c-di-GMP-responsive components. Bacterial response to environmental signals can occur on several levels: the level of individual genes and proteins (changes in gene expression, post-translational regulation), the whole-cell level (chemotaxis), and the multicellular level (biofilm formation). All signal transduction systems are energy-dependent but their energy expenditure is miniscule compared to that of the processes they regulate. A better understanding of the signal transduction mechanisms and integration of these mechanisms into the metabolic pathway model of the E. coli cell will remain major challenges for systems biology. C1 NIH, Natl Ctr Biotechnol Informat, Natl Lib Med, Bethesda, MD 20892 USA. RP Galperin, MY (reprint author), NIH, Natl Ctr Biotechnol Informat, Natl Lib Med, Bldg 10, Bethesda, MD 20892 USA. EM galperin@ncbi.nlm.nih.gov OI Galperin, Michael/0000-0002-2265-5572 NR 46 TC 1 Z9 1 U1 1 U2 1 PU SPRINGER PI DORDRECHT PA PO BOX 17, 3300 AA DORDRECHT, NETHERLANDS BN 978-1-4020-9393-7 PY 2009 BP 133 EP 148 DI 10.1007/978-1-4020-9394-4_8 D2 10.1007/978-1-4020-9394-4 PG 16 WC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Microbiology SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Microbiology GA BKK54 UT WOS:000268388500008 ER PT B AU Shiloach, J Rinas, U AF Shiloach, Joseph Rinas, Ursula BE Lee, SY TI Glucose and Acetate Metabolism in E. coli - System Level Analysis and Biotechnological Applications in Protein Production Processes SO SYSTEMS BIOLOGY AND BIOTECHNOLOGY OF ESCHERICHIA COLI LA English DT Article; Book Chapter ID HIGH-CELL-DENSITY; RECOMBINANT ESCHERICHIA-COLI; CARBOHYDRATE PHOSPHOTRANSFERASE SYSTEM; LIMITED CONTINUOUS-CULTURE; FED-BATCH FERMENTATIONS; GLOBAL GENE-EXPRESSION; GROWTH-RATE; REGULATORY PROTEIN; FLUX ANALYSIS; ENZYME-ACTIVITIES AB Escherichia coli is the main bacterial producer of heterologous proteins. The current production strategies aim at growing the bacteria to high density in order to achieve high levels of desired proteins. The major obstacle for reaching high cell densities with high product titers is the tendency of the bacteria to accumulate acetate during the unrestricted growth on glucose. Moreover, the high demand for precursors and energy required for the biosynthesis of the heterologous protein causes the cells to readjust their anabolic and catabolic reactions which, most often, aggravate the acetate problem. Implementing fed-batch protocols and employing more robust strains, such as E. coli B instead of K, can reduce acetate formation. Another approach is to implement metabolic engineering to minimize acetate formation by: (a) turning off genes which directly lead to the formation of acetate, (b) introducing genes that channel the carbon flow away from acetate towards other pathways, and (c) by reducing the glucose uptake through deleting or replacing genes of the sugar uptake system. Results show that a more general approach that focuses on global regulators and/or gene sets, encoding multiple pathways will be required to construct a robust strain capable of efficiently executing the production of recombinant proteins at high growth rates without the formation of toxic byproducts such as acetic acid. C1 [Shiloach, Joseph] NIH, Biotechnol Unit, NIDDK, Bethesda, MD 20892 USA. [Rinas, Ursula] Helmholtz Ctr Infect Res, D-38124 Braunschweig, Germany. RP Shiloach, J (reprint author), NIH, Biotechnol Unit, NIDDK, Bldg 14A,Room 173, Bethesda, MD 20892 USA. EM ljs@helix.nih.gov; uri@helmholtz-hzi.de NR 133 TC 11 Z9 11 U1 1 U2 11 PU SPRINGER PI DORDRECHT PA PO BOX 17, 3300 AA DORDRECHT, NETHERLANDS BN 978-1-4020-9393-7 PY 2009 BP 377 EP 400 DI 10.1007/978-1-4020-9394-4_18 D2 10.1007/978-1-4020-9394-4 PG 24 WC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Microbiology SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Microbiology GA BKK54 UT WOS:000268388500018 ER PT J AU Slaughter, AJ Yu, JN Koehly, LM AF Slaughter, Andrew J. Yu, Janie Koehly, Laura M. BE Salas, E Goodwin, GF Burke, CS TI Social Network Analysis: Understanding the Role of Context in Small Groups and Organizations SO TEAM EFFECTIVENESS IN COMPLEX ORGANIZATIONS: CROSS-DISCIPLINARY PERSPECTIVES AND APPROACHES SE SIOP Organizational Frontiers Series LA English DT Article; Book Chapter ID DECISION DEVELOPMENT; LOGIT-MODELS; CENTRALITY; GRAPH; PERFORMANCE; SEQUENCE; MATRIX; INDEX; TEAMS C1 [Yu, Janie] Texas A&M Univ, College Stn, TX 77843 USA. [Koehly, Laura M.] NHGRI, Social Network Methods Sect, Social & Behav Res Branch, NIH, Bethesda, MD USA. RP Slaughter, AJ (reprint author), Texas A&M Univ, College Stn, TX 77843 USA. NR 61 TC 2 Z9 2 U1 1 U2 2 PU PSYCHOLOGY PRESS PI HOVE PA 27 CHURCH ROAD, HOVE BN3 2FA, E SUSSEX, ENGLAND BN 978-0-8058-5881-5 J9 SIOP ORGAN FRONT SER PY 2009 BP 433 EP 459 PG 27 WC Psychology, Applied; Management SC Psychology; Business & Economics GA BUY94 UT WOS:000290753500018 ER PT J AU Ivanova, EV Bogatyreva, ZI Isayeva, MA Suchkova, EN Baisugurov, MA Andreyeva, AV Korotkova, AA Notkins, A Paltsev, MA Suchkov, SV AF Ivanova, E. V. Bogatyreva, Z. I. Isayeva, M. A. Suchkova, E. N. Baisugurov, M. A. Andreyeva, A. V. Korotkova, A. A. Notkins, A. Paltsev, M. A. Suchkov, S. V. TI ANTITHYROID ANTIBODIES OF VARYING SPECIFICITY IN THE PATHOGENESIS AND DIAGNOSIS OF AUTOIMMUNE THYROID DISEASES SO TERAPEVTICHESKII ARKHIV LA Russian DT Article DE antithyroid autoantibodies (autoAB); specificity of autoAB; anti-TG autoAB; anti-TPO autoAB; anti-TGPO autoAB ID AUTOANTIBODIES; THYROGLOBULIN; PEROXIDASE; CYTOTOXICITY; HORMONES; GRAVES; HEALTH; ASSAY AB Aim. To compare the possible pathogenetic and clinicodiagnostic value of antithyroid autoantibodies (autoAB) different in specificity, such as monospecific ones to thyroglobulin and thyroid peroxidase (anti-TG and anti-TPO autoAB) and bispecific ones to thyroglobulin and thyroid peroxidase simultaneously (anti-TGPO autoAB), in patients with autoimmune thyroid diseases. Materials and methods. ne sera from 240 patients with autoimmune thyroiditis (AIT) and from 124 with diffuse toxic goiter (DTG) were examined. The sera from 40 healthy donors served as a control. The sera were screened for anti-TG and anti-TPO autoAB, anti-TGPO autoAB, by employing enzyme immunoassay and/or radioimmunoassay. The results were statistically processed using the variation statistics-based programs. Results. The specific features of an autoantigenic component to thyroid tissues were found in the sera of patients with AIT and DTG. An association was established between the progression of disease and the phasic change of autoAB populations or their combinations. Conclusion. The procedure for evaluating seropositivity for antithyroid autoAB, which is referred to as non-invasive studies, can be considered as a criterion test in the diagnosis and prediction of the course of AIT and DTG. C1 [Ivanova, E. V.; Bogatyreva, Z. I.; Andreyeva, A. V.] City Clin Hosp Eighty One, Unit Endocrinol, Moscow, Russia. [Korotkova, A. A.; Paltsev, M. A.; Suchkov, S. V.] IM Sechenov Moscow Med Acad, Moscow, Russia. [Isayeva, M. A.] MedStyle Effect Med Ctr, Dept Endocrinol, Moscow, Russia. [Suchkova, E. N.; Baisugurov, M. A.] AV Lunacharsky Astrakhan State Med Acad, Clin Endocrinol, Astrakhan, Russia. [Notkins, A.] Natl Inst Maxillofacial Surg, Immunol Lab, NIH, Bethesda, MD USA. RP Ivanova, EV (reprint author), City Clin Hosp Eighty One, Unit Endocrinol, Moscow, Russia. EM iva0577@mail.ru; isaeva_marina@bk.ru; _1410_@rambler.ru; fleur@andyone.in; anotkins@mail.nih.gov; stepanova@mmascience.ru; ssuchkov@online.ru NR 23 TC 0 Z9 0 U1 0 U2 1 PU IZDATELSTVO MEDITSINA PI MOSCOW PA PETROVERIGSKII PER 6-8, K-142 MOSCOW, RUSSIA SN 0040-3660 J9 TERAPEVT ARKH JI Ter. Arkhiv PY 2009 VL 81 IS 10 BP 39 EP 45 PG 7 WC Medicine, General & Internal SC General & Internal Medicine GA 531EN UT WOS:000272646400007 PM 19947439 ER PT J AU Lenfant, C AF Lenfant, Claude TI CONTROLLING BLOOD PRESSURE: HOW WELL ARE WE DOING? SO TERAPEVTICHESKII ARKHIV LA Russian DT Article DE review; arterial pressure; prevalence; treatment ID CORONARY-HEART-DISEASE; CLINICAL-PRACTICE; GLOBAL BURDEN; PRIMARY-CARE; HYPERTENSION; MANAGEMENT; GUIDELINES; SOCIETY; IMPROVEMENT; POPULATION AB The author analyses global prevalence of arterial pressure and its impact on population mortality and disability, draws attention to insufficient efficacy of this disease treatment, low awareness of the population about this disease and compliance of the patients. To achieve target arterial pressure, cooperation is necessary between the physician and the patient. C1 NHLBI, NIH, Vancouver, WA USA. RP Lenfant, C (reprint author), NHLBI, NIH, Vancouver, WA USA. EM lenfantc@prodigy.net NR 28 TC 0 Z9 0 U1 1 U2 1 PU IZDATELSTVO MEDITSINA PI MOSCOW PA PETROVERIGSKII PER 6-8, K-142 MOSCOW, RUSSIA SN 0040-3660 J9 TERAPEVT ARKH JI Ter. Arkhiv PY 2009 VL 81 IS 5 BP 47 EP + PG 4 WC Medicine, General & Internal SC General & Internal Medicine GA 462NP UT WOS:000267361100008 PM 19537586 ER PT S AU Chaudret, R Ulmer, S van Severen, MC Gresh, N Parisel, O Cisneros, GA Darden, TA Piquemal, JP AF Chaudret, R. Ulmer, S. van Severen, M. C. Gresh, N. Parisel, O. Cisneros, G. A. Darden, T. A. Piquemal, J. -P BE Wei, DQ Wang, XJ TI Progress Towards Accurate Molecular Modeling of Metal Complexes Using Polarizable Force Fields SO THEORY AND APPLICATIONS OF COMPUTATIONAL CHEMISTRY - 2008 SE AIP Conference Proceedings LA English DT Proceedings Paper CT Conference on Theory and Applications of Computational Chemistry CY SEP 23-27, 2008 CL Shanghai, PEOPLES R CHINA SP Shanghai Jiao Tong Univ, Int Assoc Scientists Interdisciplinary Areas, Natl Sci Fdn China, Res Councils UK, Chinese Chem Soc, Canadian Hongcam Int Trade Corp, Tri Biotech, Shanghai Ctr Bioinformat Technol, KC Wong Educ Fdn, Interdisciplinary Sci, Computat Life Sci, Mol Simulat, Chem Phys & Biophys Chem, Acta Physico Chem Sinica, Journal Mol Graph & Modelling DE metals; cations; molecular mechanics; density fitting; multiscale approaches ID INTERMOLECULAR INTERACTION ENERGY; CHARGE-TRANSFER CONTRIBUTION; MECHANICS AB We present refinements of the SIBFA (Sum of Interaction Between Fragments ab initio) and GEM (Gaussian electrostatic Model) polarizable molecular mechanics procedure to represent the intermolecular interaction energies of metal cations. Improved forces fields for closed-shell, open-shell and heavy metals are discussed. Some perspectives towards a multiscale SIBFA-GEM approach using density fitting techniques are presented. C1 [Chaudret, R.; Ulmer, S.; van Severen, M. C.; Parisel, O.; Piquemal, J. -P] Univ Paris 06, UPMC, Chim Theor Lab, UMR 7616, Case Courrier 137,4 Pl Jussieu, F-75005 Paris, France. [Chaudret, R.; Ulmer, S.; van Severen, M. C.; Parisel, O.; Piquemal, J. -P] CNRS, Chim Theor Lab, UMR 7616, F-75005 Paris, France. [Gresh, N.] Univ Paris 05, UFR Biomed, Lab Pharmcochim Mol & Cellularie, U648 INSERM, F-75006 Paris, France. [Cisneros, G. A.; Darden, T. A.] NIEHS, Lab Struct Biol, Res Triangle Pk, NC 27709 USA. RP Chaudret, R (reprint author), Univ Paris 06, UPMC, Chim Theor Lab, UMR 7616, Case Courrier 137,4 Pl Jussieu, F-75005 Paris, France. RI Chaudret, Robin/C-3431-2009; Van Severen, Marie-Celine/C-3514-2009; vanseveren, marie-celine/D-2588-2009; Piquemal, Jean-Philip/B-9901-2009; Chaudret, Robin/D-6950-2012 OI Piquemal, Jean-Philip/0000-0001-6615-9426; FU French ANR (project Lasihmodo); CNRS (France); Ligue Nationale contre le Cancer (Comite Ile-de-France); Intramural Research Program of the NIH; NIEHS (USA) FX This research was supported in part by the French ANR (project Lasihmodo), CNRS (France), the Ligue Nationale contre le Cancer (Comite Ile-de-France) and by the Intramural Research Program of the NIH and NIEHS (USA). NR 25 TC 6 Z9 6 U1 0 U2 3 PU AMER INST PHYSICS PI MELVILLE PA 2 HUNTINGTON QUADRANGLE, STE 1NO1, MELVILLE, NY 11747-4501 USA SN 0094-243X BN 978-0-7354-0637-7 J9 AIP CONF PROC PY 2009 VL 1102 BP 185 EP + PG 2 WC Chemistry, Multidisciplinary; Mathematical & Computational Biology; Physics, Applied SC Chemistry; Mathematical & Computational Biology; Physics GA BJE20 UT WOS:000265089800015 ER PT J AU Nie, ZG Zorrilla, EP Madamba, SG Rice, KC Roberto, M Siggins, GR AF Nie, Zhiguo Zorrilla, Eric P. Madamba, Samuel G. Rice, Kenner C. Roberto, Marisa Siggins, George Robert TI Presynaptic CRF1 Receptors Mediate the Ethanol Enhancement of GABAergic Transmission in the Mouse Central Amygdala SO THESCIENTIFICWORLDJOURNAL LA English DT Article DE electrophysiology; alcohol; gamma aminobutyric acid; corticotrophin-releasing factor; corticotropin-releasing hormone; CRH; urocortin; stresscopin; whole-cell patch; IPSC ID CORTICOTROPIN-RELEASING-FACTOR; ANXIETY-LIKE BEHAVIOR; FACTOR-LIKE IMMUNOREACTIVITY; IMPAIRED STRESS-RESPONSE; CENTRAL-NERVOUS-SYSTEM; DEPENDENT RATS; MONOAMINERGIC AFFERENTS; CENTRAL NUCLEUS; DRUG-ADDICTION; HIGH-AFFINITY AB Corticotropin-releasing factor (CRF) is a 41-amino-acid neuropeptide involved in stress responses initiated from several brain areas, including the amygdala formation. Research shows a strong relationship between stress, brain CRF, and excessive alcohol consumption. Behavioral studies suggest that the central amygdala (CeA) is significantly involved in alcohol reward and dependence. We recently reported that the ethanol augmentation of GABAergic synaptic transmission in rat CeA involves CRF1 receptors, because both CRF and ethanol significantly enhanced the amplitude of evoked GABAergic inhibitory postsynaptic currents (IPSCs) in CeA neurons from wild-type (WT) and CRF2 knockout (KO) mice, but not in neurons of CRF1 KO mice. The present study extends these findings using selective CRF receptor ligands, gene KO models, and miniature IPSC (mIPSC) analysis to assess further a presynaptic role for the CRF receptors in mediating ethanol effects in the CeA. In whole-cell patch recordings of pharmacologically isolated GABA(A)ergic IPSCs from slices of mouse CeA, both CRF and ethanol augmented evoked IPSCs in a concentration-dependent manner, with low EC(50)s. A CRF1 (but not CRF2) KO construct and the CRF1-selective nonpeptide antagonist NIH-3 (LWH-63) blocked the augmenting effect of both CRF and ethanol on evoked IPSCs. Furthermore, the new selective CRF1 agonist stressin(1), but not the CRF2 agonist urocortin 3, also increased evoked IPSC amplitudes. Both CRF and ethanol decreased paired-pulse facilitation (PPF) of evoked IPSCs and significantly enhanced the frequency, but not the amplitude, of spontaneous miniature GABAergic mIPSCs in CeA neurons of WT mice, suggesting a presynaptic site of action. The PPF effect of ethanol was abolished in CeA neurons of CRF1 KO mice. The CRF1 antagonist NIH-3 blocked the CRF- and ethanol-induced enhancement of mIPSC frequency in CeA neurons. These data indicate that presynaptic CRF1 receptors play a critical role in permitting or mediating ethanol enhancement of GABAergic synaptic transmission in CeA, via increased vesicular GABA release, and thus may be a rational target for the treatment of alcohol abuse and alcoholism. C1 [Madamba, Samuel G.; Siggins, George Robert] Scripps Res Inst, Dept Mol & Integrat Neurosci, La Jolla, CA 92037 USA. [Madamba, Samuel G.; Siggins, George Robert] Scripps Res Inst, Alcohol Res Ctr, La Jolla, CA 92037 USA. [Nie, Zhiguo] Burnham Inst Med Res, La Jolla, CA USA. [Zorrilla, Eric P.; Roberto, Marisa] Scripps Res Inst, Comm Neurobiol Addict Disorders, La Jolla, CA 92037 USA. [Rice, Kenner C.] NIDA, Chem Biol Res Branch, Bethesda, MD 20892 USA. [Rice, Kenner C.] NIAAA, NIH, Bethesda, MD USA. RP Siggins, GR (reprint author), Scripps Res Inst, Dept Mol & Integrat Neurosci, La Jolla, CA 92037 USA. EM geobob@scripps.edu FU (Novartis Pharma) [CGP-55845A]; NIH [U01-AA10994]; NIAAA [AA06420, DA03665, NS38633]; National Institute on Drug Abuse; National Institute of Alcohol Abuse and Alcoholism; National Institute of Diabetes and Digestive and Kidney Diseases FX We thank Drs. G. Koob, P. Schweitzer, and S. Moore for helpful comments; T. Acosta for technical support; Drs. J. Rivier and W. Vale (Salk Institute) for the gift of stressin1 and Ucn 3; Drs. K.-F. Lee and W. Vale (Salk Institute) for the receptor null mice; and Drs. W. Frstl and A. Suter (Novartis Pharma) for the gift of CGP-55845A. This work was supported by NIH grants U01-AA10994 (under the INIA Consortium of the NIAAA), AA06420, DA03665, and NS38633. This work also was partially supported by the NIH Intramural Research Programs of the National Institute on Drug Abuse, the National Institute of Alcohol Abuse and Alcoholism, and the National Institute of Diabetes and Digestive and Kidney Diseases. NR 64 TC 27 Z9 27 U1 0 U2 4 PU HINDAWI PUBLISHING CORPORATION PI NEW YORK PA 410 PARK AVENUE, 15TH FLOOR, #287 PMB, NEW YORK, NY 10022 USA SN 1537-744X J9 THESCIENTIFICWORLDJO JI TheScientificWorldJOURNAL PY 2009 VL 9 BP 68 EP 85 DI 10.1100/tsw.2009.1 PG 18 WC Environmental Sciences; Multidisciplinary Sciences SC Environmental Sciences & Ecology; Science & Technology - Other Topics GA 395RW UT WOS:000262542200009 PM 19151899 ER PT J AU Quiroz, C Lujan, R Uchigashima, M Simoes, AP Lerner, TN Borycz, J Kachroo, A Canas, PM Orru, M Schwarzschild, MA Rosin, DL Kreitzer, AC Cunha, RA Watanabe, M Ferre, S AF Quiroz, Cesar Lujan, Rafael Uchigashima, Motokazu Simoes, Ana Patricia Lerner, Talia N. Borycz, Janusz Kachroo, Anil Canas, Paula M. Orru, Marco Schwarzschild, Michael A. Rosin, Diane L. Kreitzer, Anatol C. Cunha, Rodrigo A. Watanabe, Masahiko Ferre, Sergi TI Key Modulatory Role of Presynaptic Adenosine A(2A) Receptors in Cortical Neurotransmission to the Striatal Direct Pathway SO THESCIENTIFICWORLDJOURNAL LA English DT Article DE adenosine A(2A) receptor; striatum; basal ganglia; medium spiny neuron; glutamatergic neurotransmission; presynaptic receptors ID CENTRAL-NERVOUS-SYSTEM; MEDIUM SPINY NEURONS; LONG-TERM POTENTIATION; BASAL GANGLIA; NUCLEUS-ACCUMBENS; DOPAMINE RELEASE; RAT STRIATUM; ULTRASTRUCTURAL-LOCALIZATION; PARKINSONS-DISEASE; DORSAL STRIATUM AB Basal ganglia processing results from a balanced activation of direct and indirect striatal efferent pathways, which are controlled by dopamine D-1 and D-2 receptors, respectively. Adenosine A(2A) receptors are considered novel antiparkinsonian targets, based on their selective postsynaptic localization in the indirect pathway, where they modulate D-2 receptor function. The present study provides evidence for the existence of an additional, functionally significant, segregation of A(2A) receptors at the presynaptic level. Using integrated anatomical, electrophysiological, and biochemical approaches, we demonstrate that presynaptic A(2A) receptors are preferentially localized in cortical glutamatergic terminals that contact striatal neurons of the direct pathway, where they exert a selective modulation of corticostriatal neurotransmission. Presynaptic striatal A(2A) receptors could provide a new target for the treatment of neuropsychiatric disorders. C1 [Quiroz, Cesar; Borycz, Janusz; Orru, Marco; Ferre, Sergi] Natl Inst Drug Abuse, IRP, NIH, DHHS, Baltimore, MD USA. [Lujan, Rafael] Univ Castilla La Mancha, Fac Med, Dept Ciencias Med, Albacete, Spain. [Uchigashima, Motokazu] Hokkaido Univ, Sch Med, Dept Anat, Sapporo, Hokkaido 060, Japan. [Simoes, Ana Patricia; Canas, Paula M.; Cunha, Rodrigo A.] Univ Coimbra, Inst Biochem, Fac Med, CNC, Coimbra, Portugal. [Lerner, Talia N.; Kreitzer, Anatol C.] Univ Calif San Francisco, Gladstone Inst Neurol Dis, San Francisco, CA 94143 USA. [Lerner, Talia N.; Kreitzer, Anatol C.] Univ Calif San Francisco, Dept Physiol, San Francisco, CA 94143 USA. [Kachroo, Anil; Schwarzschild, Michael A.] MassGen Inst Neurodegenerat Dis, Dept Neurol, Charlestown, MA USA. [Rosin, Diane L.] Univ Virginia, Hlth Sci Ctr, Dept Pharmacol, Charlottesville, VA 22908 USA. RP Ferre, S (reprint author), Natl Inst Drug Abuse, IRP, NIH, DHHS, Baltimore, MD USA. EM sferre@intra.nida.nih.gov RI WATANABE, Masahiko/A-4055-2012; Uchigashima, Motokazu/C-5715-2012; Ferre, Sergi/K-6115-2014; Canas, Paula/Q-2101-2015; Cunha, Rodrigo/E-7475-2015; OI Ferre, Sergi/0000-0002-1747-1779; Canas, Paula/0000-0002-4091-6406; Cunha, Rodrigo/0000-0003-2550-6422; Simoes, Ana Patricia/0000-0003-2937-7015 FU National Institute on Drug Abuse; CHDI Foundation; Consejeria de Educacion y Ciencia de la Junta de Comunidades de Castilla-La Mancha [PAI08-0174-6967]; Fundacao para a Ciencia e Tecnologia [FCT-PTDC/SAU-NEU/81064/2006]; National Institutes of Health [RO1 NS054978] FX The authors would like to thank Mrs. Mar a Jose Cabanero for the excellent technical assistance and Dr. Robert H. Edwards, UCSF, San Francisco, for kindly providing the vGluT1 receptor antibody. Work supported by the intramural funds of the National Institute on Drug Abuse, CHDI Foundation, the "Consejeria de Educacion y Ciencia de la Junta de Comunidades de Castilla-La Mancha" (PAI08-0174-6967) to RL, Fundacao para a Ciencia e Tecnologia (FCT-PTDC/SAU-NEU/81064/2006) to RAC, National Institutes of Health RO1 NS054978. NR 55 TC 45 Z9 45 U1 0 U2 6 PU HINDAWI PUBLISHING CORPORATION PI NEW YORK PA 410 PARK AVENUE, 15TH FLOOR, #287 PMB, NEW YORK, NY 10022 USA SN 1537-744X J9 THESCIENTIFICWORLDJO JI TheScientificWorldJOURNAL PY 2009 VL 9 BP 1321 EP 1344 DI 10.1100/tsw.2009.143 PG 24 WC Environmental Sciences; Multidisciplinary Sciences SC Environmental Sciences & Ecology; Science & Technology - Other Topics GA 544SJ UT WOS:000273679300059 PM 19936569 ER PT S AU Smirnov, AV Combs, CA Balaban, RS Tang, K Knutson, JR AF Smirnov, Aleksandr V. Combs, Christian A. Balaban, Robert S. Tang, Kevin Knutson, Jay R. BE Conchello, JA Cogswell, CJ Wilson, T TI A hybrid global fitting algorithm for decay-associated images from fluorescence lifetime image microscopy data SO THREE-DIMENSIONAL AND MULTIDIMENSIONAL MICROSCOPY: IMAGE ACQUISITION AND PROCESSING XVI SE Proceedings of SPIE-The International Society for Optical Engineering LA English DT Proceedings Paper CT Conference on Three-Dimensional and Multidimensional Microscopy - Image Acquisition and Processing XVI CY JAN 26-29, 2009 CL San Jose, CA SP SPIE DE deconvolution; global fitting; FLIM; DAS; DAI; NADH; free-to-bound ratio ID ANISOTROPY; SPECTRA; NADH AB Fluorescence lifetime imaging microscopy ("FLIM") is a technique for measuring fluorescence lifetime(s) at each pixel of a microscope image. Imaging of fluorescence lifetimes enables biochemical reactions to be followed at each microscopically resolvable location within the cell. FLIM has thus become very useful for biomedical tissue imaging. Global analysis [1] is a method of recovering fluorescence decay parameters from either time-resolved emission spectra to yield Decay-Associated Spectra [2], or equivalently, from FLIM datasets to yield Decay-Associated Images ("DAI"). Global analysis enables a sensitive and non-invasive probe of metabolic state of intracellular molecules such as NADH. Using linkage information, such as the spatial invariance of the lifetime of each fluorescent species in the image, global analysis can recover lifetimes and amplitudes more accurately than traditional pixel-by-pixel analysis. Here, we explain a method to analyze FLIM data so that more accurate lifetimes and DAIs can be computed in a reasonable time. This approach involves coupling an iterative global analysis with linear algebraic operations. C1 [Smirnov, Aleksandr V.; Combs, Christian A.; Balaban, Robert S.; Knutson, Jay R.] NHLBI, NIH, Bethesda, MD 20892 USA. RP Smirnov, AV (reprint author), NHLBI, NIH, 10 Ctr Dr, Bethesda, MD 20892 USA. NR 8 TC 0 Z9 0 U1 0 U2 0 PU SPIE-INT SOC OPTICAL ENGINEERING PI BELLINGHAM PA 1000 20TH ST, PO BOX 10, BELLINGHAM, WA 98227-0010 USA SN 0277-786X BN 978-0-8194-7430-8 J9 P SOC PHOTO-OPT INS PY 2009 VL 7184 AR 71841D DI 10.1117/12.809844 PG 6 WC Microscopy; Optics; Imaging Science & Photographic Technology SC Microscopy; Optics; Imaging Science & Photographic Technology GA BSL65 UT WOS:000284868100023 ER PT B AU Shields, AE Fullerton, SM Olden, K AF Shields, Alexandra E. Fullerton, Stephanie M. Olden, Kenneth BE Koh, HK TI Genes, Environment, and Cancer Disparities SO TOWARD THE ELIMINATION OF CANCER DISPARITIES: CLINICAL AND PUBLIC HEALTH PERSPECTIVES LA English DT Article; Book Chapter ID MICROSOMAL EPOXIDE HYDROLASE; NONPOLYPOSIS COLORECTAL-CANCER; CUMULATIVE CIGARETTE-SMOKING; GENOME-WIDE ASSOCIATION; DNA-REPAIR GENES; S-TRANSFERASE M1; BREAST-CANCER; LUNG-CANCER; HEALTH DISPARITIES; PROSTATE-CANCER C1 [Shields, Alexandra E.] Harvard MGH Ctr Genom Vulnerable Populat & Hlth D, Boston, MA 02115 USA. [Fullerton, Stephanie M.] Univ Washington, Dept Med Hist & Eth, Seattle, WA 98195 USA. [Fullerton, Stephanie M.] Univ Washington, Ctr Genom & Healthcare Equal, Seattle, WA 98195 USA. [Olden, Kenneth] NIEHS, Mol Carcinogenesis Lab, NIH, Res Triangle Pk, NC 27709 USA. [Shields, Alexandra E.] Harvard Univ, Sch Med, Dept Med, Boston, MA USA. [Shields, Alexandra E.] Massachusetts Gen Hosp Partners HealthCare, Inst Hlth Policy, Boston, MA USA. RP Shields, AE (reprint author), Harvard MGH Ctr Genom Vulnerable Populat & Hlth D, Boston, MA 02115 USA. OI Fullerton, Stephanie/0000-0002-0938-6048 NR 116 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013, UNITED STATES BN 978-0-387-89442-3 PY 2009 BP 49 EP 82 DI 10.1007/978-0-387-89443-0_3 D2 10.1007/978-0-387-89443-0 PG 34 WC Health Policy & Services; Public, Environmental & Occupational Health SC Health Care Sciences & Services; Public, Environmental & Occupational Health GA BKN85 UT WOS:000268727300003 ER PT J AU Renne, R Brix, A Harkema, J Herbert, R Kittel, B Lewis, D March, T Nagano, K Pino, M Rittinghausen, S Rosenbruch, M Tellier, P Wohrmann, T AF Renne, Roger Brix, Amy Harkema, Jack Herbert, Ron Kittel, Birgit Lewis, David March, Thomas Nagano, Kasuke Pino, Michael Rittinghausen, Susanne Rosenbruch, Martin Tellier, Pierre Wohrmann, Thomas TI Proliferative and Nonproliferative Lesions of the Rat and Mouse Respiratory Tract SO TOXICOLOGIC PATHOLOGY LA English DT Review DE respiratory system; lesions of the rat respiratory system; lesions of the mouse respiratory system ID GENE-RELATED PEPTIDE; SPRAGUE-DAWLEY RATS; FISCHER 344 RATS; BETA-OXIDIZED DIPROPYLNITROSAMINE; CYTOKERATIN EXPRESSION PATTERNS; TOBACCO-SPECIFIC NITROSAMINE; TITANIUM-DIOXIDE PARTICLES; LONG-TERM INHALATION; NASAL CAVITY TUMORS; CLARA CELL ADENOMAS AB The INHAND Project (International Harmonization of and Diagnostic Criteria for Lesions in Rats and Mice) is a joint initiative of the Societies of Toxicologic Pathology from Europe (ESTP). Great Britain (BSTP). Japan (JSPT) and North America (STP) to develop an internationally-accepted nomenclature for proliferative and non-proliferative lesions in laboratory animals. The purpose of this publication is to provide a standardized nomenclature for classifying microscopic lesions observed in the respiratory tract of laboratory rats and mice, with color photomicrographs illustrating examples of some lesions. The standardized nomenclature presented in this document is also available electronically on the internet (http.//www gorem org/) Sources of material included histopathology databases from government, academia, and industrial laboratories throughout the world. Content includes spontaneous developmental and aging lesions as well as lesions induced by exposure to test materials. A widely accepted and utilized international harmonization of nomenclature for respiratory tract lesions in laboratory animals will decrease confusion among regulatory and scientific research organizations in different countries and provide a common language to increase and enrich international exchanges of information among toxicologists and pathologists. C1 [Renne, Roger] Roger Renne ToxPath Consulting, Sumner, WA USA. [Brix, Amy] Expt Pathol Labs, Res Triangle Pk, NC USA. [Harkema, Jack] Michigan State Univ, Coll Vet Med, E Lansing, MI 48824 USA. [Herbert, Ron] Natl Inst Environm Hlth Sci, Res Triangle Pk, NC USA. [Kittel, Birgit] Novartis Inst BioMed Res, Basel, Switzerland. [Lewis, David] GlaxoSmithKline Inc, Ware, Herts, England. [March, Thomas] Lovelace Resp Res Inst, Albuquerque, NM USA. [Nagano, Kasuke] Japan Ind Safety & Hlth Assoc, Japan Bioassay Res Ctr, Kanagawa, Japan. [Pino, Michael] Sanofi Aventis, Bridgewater, NJ USA. [Rittinghausen, Susanne] Fraunhofer Inst Toxicol & Expt Med, Hannover, Germany. [Rosenbruch, Martin] Bayer Schering Pharma AG, Wuppertal, Germany. [Tellier, Pierre] Charles River Labs, Montreal, PQ, Canada. [Wohrmann, Thomas] Nycomed GmbH, Inst Pharmacol & Preclin Drug Safety Haidkrugsweg, Barsbuttel, Germany. RP Renne, R (reprint author), Roger Renne ToxPath Consulting, Sumner, WA USA. NR 275 TC 52 Z9 54 U1 1 U2 6 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 0192-6233 J9 TOXICOL PATHOL JI Toxicol. Pathol. PY 2009 VL 37 IS 7 BP 5S EP 73S DI 10.1177/0192623309353423 PG 69 WC Pathology; Toxicology SC Pathology; Toxicology GA 529YS UT WOS:000272556100001 PM 20032296 ER PT J AU Wang, NN Symons, JD Zhang, H Jia, ZJ Gonzalez, FJ Yang, TX AF Wang, Ningning Symons, J. David Zhang, Hui Jia, Zhanjun Gonzalez, Frank J. Yang, Tianxin TI Distinct Functions of Vascular Endothelial and Smooth Muscle PPAR gamma in Regulation of Blood Pressure and Vascular Tone SO TOXICOLOGIC PATHOLOGY LA English DT Article DE PPAR gamma; rosiglitazone; endothelial cells; smooth muscle cells; blood pressure ID ACTIVATED-RECEPTOR-GAMMA; CELL-GROWTH; INSULIN-RESISTANCE; GENE-EXPRESSION; DEFICIENT MICE; C57BL/6J MICE; THIAZOLIDINEDIONES; HYPERTENSION; DELETION; OBESITY AB Thiazolidinediones (TZDs) are peroxisome proliferators-activated receptor gamma ( PPAR.) activators that exhibit antihypertensive and vasculo-protective effects. Here we describe the use of Tie2Cre/flox and SM22Cre/flox mice, which respectively lacked PPAR gamma in the endothelium and the smooth muscle, to study vascular function of PPAR gamma. Rosiglitazone (RGZ) induced a similar blood pressure (BP)-lowering effect in deoxycorticosterone acetate ( DOCA) salt-treated PPAR gamma(f/f) and SM22Cre/flox mice, whereas Tie2Cre/flox mice were completely resistant to this effect. The femoral arteries lacking endothelial PPAR gamma exhibited increased reactivity to various vasoconstrictors without a significant alteration in acetylcholine-induced relaxation. In sharp contrast, the vasculature lacking smooth muscle PPAR gamma had blunted sensitivity to alpha 1-adrenergic agents but enhanced sensitivity to acetylcholine. Our results demonstrated endothelium but not smooth muscle as the site for TZD-induced BP-lowering effect and also uncovered distinct functions of endothelial and smooth muscle PPAR gamma in regulation of vascular tone. C1 [Wang, Ningning; Zhang, Hui; Jia, Zhanjun; Yang, Tianxin] Univ Utah, Dept Internal Med, Salt Lake City, UT 84132 USA. [Wang, Ningning; Zhang, Hui; Jia, Zhanjun; Yang, Tianxin] Salt Lake Vet Affairs Med Ctr, Salt Lake City, UT USA. [Symons, J. David] Univ Utah, Coll Hlth, Salt Lake City, UT 84132 USA. [Symons, J. David] Univ Utah, Div Endocrinol Diabet & Metab, Salt Lake City, UT 84132 USA. [Gonzalez, Frank J.] NCI, NIH, Bethesda, MD 20892 USA. RP Yang, TX (reprint author), Univ Utah, Dept Internal Med, 30 N 1900 E,Rm 4R312, Salt Lake City, UT 84132 USA. EM Tianxin.Yang@hsc.utah.edu FU Merit Review from the Department of Veterans Affairs [RO-1 HL079453]; National Institute of Health FX This work was supported by Merit Review from the Department of Veterans Affairs as well as RO-1 HL079453 from National Institute of Health ( to T. Yang). NR 37 TC 17 Z9 18 U1 0 U2 1 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 0192-6233 J9 TOXICOL PATHOL JI Toxicol. Pathol. PD JAN PY 2009 VL 37 IS 1 BP 21 EP 27 DI 10.1177/0192623308328545 PG 7 WC Pathology; Toxicology SC Pathology; Toxicology GA 463XE UT WOS:000267466500004 PM 19075043 ER PT J AU Singh, BP Nyska, A Johansson, SL Malarkey, DE Hooth, MJ AF Singh, B. P. Nyska, A. Johansson, S. L. Malarkey, D. E. Hooth, M. J. TI Urethral Transitional Carcinoma and Hyperplasia in Male B6c3f1 Mice Treated with Tetrachloroazobenzene (TCAB) SO TOXICOLOGIC PATHOLOGY LA English DT Meeting Abstract C1 [Singh, B. P.; Malarkey, D. E.; Hooth, M. J.] NIEHS, Natl Toxicol Program, Res Triangle Pk, NC 27709 USA. [Johansson, S. L.] Univ Nebraska Med Ctr, Eppley Canc Ctr, Dept Pathol & Microbiol, Omaha, NE USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 0192-6233 J9 TOXICOL PATHOL JI Toxicol. Pathol. PD JAN PY 2009 VL 37 IS 1 MA P10 BP 126 EP 126 PG 1 WC Pathology; Toxicology SC Pathology; Toxicology GA 463XE UT WOS:000267466500024 ER PT J AU Ramot, Y Nyska, A Lieuallen, W Maly, A Zlotogorski, A Flake, G Kissling, G Brix, A Malarkey, D Hooth, M AF Ramot, Yuval Nyska, Abraham Lieuallen, Warren Maly, Alex Zlotogorski, Abraham Flake, Gordon Kissling, Grace Brix, Amy Malarkey, David Hooth, Michelle TI Inflammatory and Chloracne-Like Skin Lesions in B6C3F1 Mice Exposed to Tetrachloroazobenzene (TCAB) for Two Years SO TOXICOLOGIC PATHOLOGY LA English DT Meeting Abstract C1 [Ramot, Yuval; Maly, Alex; Zlotogorski, Abraham] Hadassah Hebrew Univ, Med Ctr, Jerusalem, Israel. [Nyska, Abraham] Tel Aviv Univ, IL-69978 Tel Aviv, Israel. [Lieuallen, Warren] Pathol Associates Inc, Charles River Labs, Durham, NC USA. [Flake, Gordon; Brix, Amy; Malarkey, David] Natl Inst Environm Hlth Sci, Lab Expt Pathol, Res Triangle Pk, NC USA. [Kissling, Grace] Natl Inst Environm Hlth Sci, Biostat Branch, Res Triangle Pk, NC USA. [Hooth, Michelle] Natl Inst Environm Hlth Sci, Toxicol Operat Branch, Res Triangle Pk, NC USA. NR 0 TC 0 Z9 0 U1 0 U2 2 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 0192-6233 J9 TOXICOL PATHOL JI Toxicol. Pathol. PD JAN PY 2009 VL 37 IS 1 MA P44 BP 137 EP 137 PG 1 WC Pathology; Toxicology SC Pathology; Toxicology GA 463XE UT WOS:000267466500058 ER PT J AU Brin, YS Nyska, M Mizrahi, B Golenser, J Maoz, G Domb, AJ Peddada, S Nyska, A AF Brin, Yaron S. Nyska, Meir Mizrahi, Boaz Golenser, Jacob Maoz, Guy Domb, Avi J. Peddada, Shyamal Nyska, Abraham TI Treatment of Osteomyelitis in Rats by Injection of Degradable Polymer-Releasing Gentamicin SO TOXICOLOGIC PATHOLOGY LA English DT Meeting Abstract C1 [Brin, Yaron S.; Nyska, Meir; Maoz, Guy] Meir Med Ctr, Dept Orthopaed Surg, Kefar Sava, Israel. [Mizrahi, Boaz; Domb, Avi J.] Hebrew Univ Jerusalem, Sch Pharm, Dept Med Chem & Nat Prod, IL-91120 Jerusalem, Israel. [Golenser, Jacob] Hebrew Univ Jerusalem, Kuvin Ctr Study Infect & Trop Dis, Dept Parasitol, IL-91120 Jerusalem, Israel. [Peddada, Shyamal] NIEHS, Biostat Branch, NIH, US Dept HHS, Res Triangle Pk, NC 27709 USA. [Nyska, Abraham] Tel Aviv Univ, Israel Sackler Sch Med, IL-69978 Tel Aviv, Israel. RI Peddada, Shyamal/D-1278-2012 NR 0 TC 0 Z9 0 U1 0 U2 0 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 0192-6233 J9 TOXICOL PATHOL JI Toxicol. Pathol. PD JAN PY 2009 VL 37 IS 1 MA P63 BP 142 EP 143 PG 2 WC Pathology; Toxicology SC Pathology; Toxicology GA 463XE UT WOS:000267466500076 ER PT J AU Kissling, GE Malarkey, DE Vallant, MK Johnson, JD Hejtmancik, MR Herbert, RA Boorman, GA AF Kissling, Grace E. Malarkey, David E. Vallant, Molly K. Johnson, Jerry D. Hejtmancik, Milton R. Herbert, Ronald A. Boorman, Gary A. TI Evaluation of Dichloroacetic Acid for Carcinogenicity in Genetically Modified Tg.AC Hemizygous and p53 Haploinsufficient Mice SO TOXICOLOGICAL SCIENCES LA English DT Article ID TRANSGENIC MOUSE MODELS; LIVER-TUMOR INDUCTION; MALE B6C3F(1) MOUSE; DRINKING-WATER; DOSE-RESPONSE; TRICHLOROACETIC-ACID; HEPATOCARCINOGENICITY; TRICHLOROETHYLENE; EXPRESSION; BIOASSAYS AB There has been considerable interest in the use of genetically modified mice for detecting potential environmental carcinogens. For this reason, the National Toxicology Program has been evaluating Tg.AC hemizygous and p53 haploinsufficient mice as models to detect potential carcinogens. It was reasoned that these mouse models might also prove more effective than standard rodent models in evaluating the numerous disinfection byproducts that are found in low concentrations in drinking water. Dichloroacetic acid (DCA) is one of the most frequently found disinfection byproducts and DCA has been consistently shown to cause hepatocellular tumors in rats and mice in standard rodent studies. Tg.AC hemizygous and p53 haploinsufficient mice were exposed in the drinking water to DCA for up to 41 weeks. In a second study Tg.AC mice were subjected to dermal DCA exposure for up to 39 weeks. Increased incidences and severity of cytoplasmic vacuolization of hepatocytes were seen in the p53 mice, but there was no evidence of carcinogenic activity at exposures of up to 2000 mg/l in the drinking water. Increased incidences and severity of cytoplasmic vacuolization of hepatocytes were seen in the drinking water study with Tg.AC mice and a modest non-dose-related increase in pulmonary adenomas was observed in males exposed to 1000 mg/l in the drinking water. Dermal exposure up to 500 mg/kg for 39 weeks resulted in increased dermal papillomas at the site of application in Tg.AC mice. No significant increase in papillomas under the same study conditions was seen in the 26-week study. For DCA under these study conditions, the p53 and Tg.AC mice appear less sensitive to hepatocarcinogenesis than standard rodent models. These results suggest caution for the use of Tg.AC and p53 mice to screen unknown chemicals in drinking water for potential carcinogenicity. C1 [Kissling, Grace E.] NIEHS, Environm Dis & Med Program, Res Triangle Pk, NC 27709 USA. [Malarkey, David E.; Vallant, Molly K.; Herbert, Ronald A.; Boorman, Gary A.] NIEHS, Environm Toxicol Program, Res Triangle Pk, NC 27709 USA. [Johnson, Jerry D.; Hejtmancik, Milton R.] Battelle Columbus Operat, Hlth Div, Columbus, OH 43201 USA. RP Kissling, GE (reprint author), NIEHS, Environm Dis & Med Program, MD A3-03,POB 12233,111 TW Alexander Dr, Res Triangle Pk, NC 27709 USA. EM kissling@niehs.nih.gov FU National Institutes of Health; National Institute of Environmental Health Sciences (NIEHS) [NO1-ES-65406] FX Intramural Research Program of the National Institutes of Health, National Institute of Environmental Health Sciences (NIEHS); and NIEHS contract (NO1-ES-65406) to Battelle Laboratories, Columbus, OH 43201, conducted the in-life portion of the study. NR 27 TC 3 Z9 3 U1 0 U2 1 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 1096-6080 J9 TOXICOL SCI JI Toxicol. Sci. PD JAN PY 2009 VL 107 IS 1 BP 19 EP 26 DI 10.1093/toxsci/kfn228 PG 8 WC Toxicology SC Toxicology GA 386NM UT WOS:000261889900003 PM 18974089 ER PT J AU Marchetti, F Bishop, J Xiu, LW Wyrobek, AJ AF Marchetti, Francesco Bishop, Jack Xiu Lowe Wyrobek, Andrew J. TI Chromosomal Mosaicism in Mouse Two-Cell Embryos after Paternal Exposure to Acrylamide SO TOXICOLOGICAL SCIENCES LA English DT Article ID UNSCHEDULED DNA-SYNTHESIS; HUMAN PREIMPLANTATION EMBRYOS; CONFINED PLACENTAL MOSAICISM; INDUCED CELL DEATH; MALE GERM-CELLS; MALE-MICE; HERITABLE TRANSLOCATIONS; CLEAVAGE DIVISIONS; MAILLARD REACTION; LOCUS MUTATIONS AB Chromosomal mosaicism in human preimplantation embryos is a common cause of spontaneous abortions, however, our knowledge of its etiology is limited. We used multicolor fluorescence in situ hybridization painting to investigate whether paternally transmitted chromosomal aberrations result in mosaicism in mouse two-cell embryos. Paternal exposure to acrylamide, an important industrial chemical also found in tobacco smoke and generated during the cooking process of starchy foods, produced significant increases in chromosomally defective two-cell embryos, however, the effects were transient primarily affecting the postmeiotic stages of spermatogenesis. Comparisons with our previous study of zygotes demonstrated similar frequencies of chromosomally abnormal zygotes and two-cell embryos suggesting that there was no apparent selection against numerical or structural chromosomal aberrations. However, the majority of affected two-cell embryos were mosaics showing different chromosomal abnormalities in the two blastomeric metaphases. Analyses of chromosomal aberrations in zygotes and two-cell embryos showed a tendency for loss of acentric fragments during the first mitotic division of embryogenesis, whereas both dicentrics and translocations apparently underwent proper segregation. These results suggest that embryonic development can proceed up to the end of the second cell cycle of development in the presence of abnormal paternal chromosomes and that even dicentrics can persist through cell division. The high incidence of chromosomally mosaic two-cell embryos suggests that the first mitotic division of embryogenesis is prone to missegregation errors and that paternally transmitted chromosomal abnormalities increase the risk of missegregation leading to embryonic mosaicism. C1 [Marchetti, Francesco; Xiu Lowe; Wyrobek, Andrew J.] Univ Calif Berkeley, Lawrence Berkeley Lab, Div Life Sci, Berkeley, CA 94720 USA. [Marchetti, Francesco; Xiu Lowe; Wyrobek, Andrew J.] Lawrence Livermore Natl Lab, Biosci Directorate, Livermore, CA 94550 USA. [Bishop, Jack] NIEHS, Res Triangle Pk, NC 27709 USA. [Xiu Lowe] Kaiser Permanente Med Grp Inc, Dept Psychiat, Hayward, CA 94545 USA. RP Marchetti, F (reprint author), Univ Calif Berkeley, Lawrence Berkeley Lab, Div Life Sci, 1 Cyclotron Rd, Berkeley, CA 94720 USA. EM fmarchetti@lbl.gov OI Marchetti, Francesco/0000-0002-9435-4867 FU National Institute of Environmental Health Sciences through an NIEHS/DOE Interagency Agreement [Y01ES-10203-00]; California Tobacco Related Disease Research Program [13RT-140A] FX National Institute of Environmental Health Sciences through an NIEHS/DOE Interagency Agreement (grant number Y01ES-10203-00) to A. W. J. and F. M.; and California Tobacco Related Disease Research Program (grant number 13RT-140A) to F. M. NR 69 TC 8 Z9 8 U1 0 U2 4 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 1096-6080 J9 TOXICOL SCI JI Toxicol. Sci. PD JAN PY 2009 VL 107 IS 1 BP 194 EP 205 DI 10.1093/toxsci/kfn209 PG 12 WC Toxicology SC Toxicology GA 386NM UT WOS:000261889900019 PM 18930949 ER PT J AU Brimfield, AA Mancebo, AM Mason, RP Jiang, JJ Siraki, AG Novak, MJ AF Brimfield, A. A. Mancebo, A. M. Mason, R. P. Jiang, J. J. Siraki, A. G. Novak, M. J. TI Free radical production from the interaction of 2-chloroethyl vesicants (mustard gas) with pyridine nucleotide-driven flavoprotein electron transport systems SO TOXICOLOGY AND APPLIED PHARMACOLOGY LA English DT Article DE Chemical warfare; Flavoenzyme; Chloroethyl mustards; Onium ion; Enzymatic reduction; Electron transport; Free radical; EPR ID NITRIC-OXIDE SYNTHASE; SULFUR MUSTARD; THIOREDOXIN REDUCTASE; SULFONIUM SALTS; IN-VITRO; MECHANISM; TOXICITY; DRUG; IDENTIFICATION; PROCARBAZINE AB The biochemical sequelae to chloroethyl mustard exposure correspond very well to toxic processes initiated by free radicals. Additionally, mustard solutions contain spontaneously formed cyclic onium ions which produce carbon free radicals when reduced electrochemically. Therefore, we hypothesized that the onium ions of sulfur or nitrogen mustards might produce carbon free radicals upon being reduced enzymatically, and that these radicals might constitute a metabolic activation. We set out to document radical production using an in vitro metabolic system and electron paramagnetic resonance (EPR). Our system consisted of NADPH, one of several pyridine nucleotide-driven flavoprotein reductases, cytochrome c as a terminal electron acceptor, various sulfur or nitrogen mustards and the spin trap alpha-[4-pyridyl-1-oxide]-N-tertbutylnitrone in buffer. Reactions were started by adding the reductase to the other materials, vortexing and immediately transferring the mixture to a 10 mm EPR flat cell. Repeated scans on a Bruker ESP 300E EPR spectrometer produced a triplet of doublets with hyperfine splitting constants of a(N) = 15.483 G and a(H)=2.512 G. The outcome supported our hypothesis that carbon-centered free radicals are produced when mustard-related onium ions are enzymatically reduced. The EPR results varied little with the chloroethyl compound used or with porcine or human cytochrome P450 reductase, the reductase domain of rat brain neuronal nitric oxide synthase or rat liver thioredoxin reductase. Our results offer new insight into the basis for mustard-induced vesication and the outcome of exposure to different mustards. The free radical model provides an explanation for similarities in the lesions arising from mustard exposure and energy-based lesions such as those from heat, ultraviolet and nuclear radiation as well as damage across tissue types such as skin, eyes or airway epithelium. Published by Elsevier Inc. C1 [Brimfield, A. A.; Mancebo, A. M.] USA, Med Res Inst Chem Def, Aberdeen Proving Ground, MD 21010 USA. [Mason, R. P.; Jiang, J. J.; Siraki, A. G.] NIEHS, Lab Pharmacol & Chem, Res Triangle Pk, NC 27709 USA. [Novak, M. J.] Florida Inst Technol, Dept Chem, Melbourne, FL 32901 USA. RP Brimfield, AA (reprint author), USA, Med Res Inst Chem Def, Aberdeen Proving Ground, MD 21010 USA. EM alan.a.brimfield@us.army.mil FU Defense Threat Reduction Agency; Joint Science and Technology Office; U.S. Army Medical Research and Materiel Command; Intramural Research Program of the NIH; [17-00-2-008] FX This work was supported by the Defense Threat Reduction Agency - Joint Science and Technology Office, Medical S and T Division and, in part, by award number DAMD 17-00-2-008 from the U.S. Army Medical Research and Materiel Command. This research was also Supported in part by the Intramural Research Program of the NIH, National Institute of Environmental Health Sciences. Thanks are due to Dr. Carmen Arroyo and Mr. Brendon Gallagher of USAMRICD for helping to get this work started. We are grateful to Professor Bettie Sue Masters of the Department of Biochemistry, University of Texas Health Sciences Center, San Antonio, for the kind gift of recombinant rat brain nNOS reductase domain and recombinant porcine liver NADPHcytochrome P450 redUctase and to Dr. Thomas M. Shea of that laboratory for generous advice. And finally, we would like to express our thanks to Dr. MarkA. Zottola and Dr. Sunil D. Soni of USAMRICD for discussions that were inevitably helpful and enlightening. NR 43 TC 16 Z9 17 U1 0 U2 5 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0041-008X EI 1096-0333 J9 TOXICOL APPL PHARM JI Toxicol. Appl. Pharmacol. PD JAN 1 PY 2009 VL 234 IS 1 BP 128 EP 134 DI 10.1016/j.taap.2008.10.002 PG 7 WC Pharmacology & Pharmacy; Toxicology SC Pharmacology & Pharmacy; Toxicology GA 397SL UT WOS:000262682300014 PM 18977373 ER PT S AU Preuss, ML Weidman, P Nielsen, E AF Preuss, Mary L. Weidman, Peggy Nielsen, Erik BA Segev, N BF Segev, N TI How We Study Protein Transport SO TRAFFICKING INSIDE CELLS: PATHWAYS, MECHANISMS AND REGULATION SE Molecular Biology Intelligence Unit LA English DT Article; Book Chapter ID GREEN-FLUORESCENT PROTEIN; CELL-FREE SYSTEM; VESICULAR STOMATITIS-VIRUS; RECEPTOR-MEDIATED ENDOCYTOSIS; DENSITY-LIPOPROTEIN RECEPTOR; RESONANCE ENERGY-TRANSFER; YEAST SECRETORY PATHWAY; PERFORATED MDCK CELLS; TO-GOLGI TRANSPORT; IN-VITRO AB For the greater part of the last century, research in the field of protein transport was synonymous with microscopy. Before the end of the century, this view was dramatically changed by the emergence of innovative genetic, molecular and biochemical approaches that revolutionized and invigorated the field. Far from being displaced as an essential tool, microscopy techniques have also evolved. What was once largely a science of "dead cells" has been transformed into a window on the inner workings of living cells. The objective of this chapter is to provide an overview of the major approaches that are employed in the analysis of protein transport within the membrane trafficking system of eukaryotic cells. In particular, we discuss the identification of several of the common model cargo proteins for studying both secretory and endocytic membrane trafficking in both mammalian and yeast systems. We then discuss the development of both in vivo and in vitro techniques to study the transport of these model cargo proteins within cells, and explain some of the common principles involved in these assays. Finally, we discuss some of the recent advances in imaging techniques and technology that have driven the recent "renaissance" in the use of microscopic techniques in the investigation of membrane trafficking events in living cells. C1 [Nielsen, Erik] Univ Michigan, Dept Mol Cellular & Dev Biol, Ann Arbor, MI 48109 USA. [Weidman, Peggy] NIGMS, Off Sci Review, Bethesda, MD USA. [Preuss, Mary L.] Donald Danforth Plant Sci Ctr, St Louis, MO USA. RP Nielsen, E (reprint author), Univ Michigan, Dept Mol Cellular & Dev Biol, 830 N Univ Ave, Ann Arbor, MI 48109 USA. EM nielsene@umich.edu RI Nielsen, Erik/G-5843-2013 NR 182 TC 0 Z9 0 U1 0 U2 3 PU LANDES BIOSCIENCE PI GEORGETOWN PA 810 S CHURCH ST, GEORGETOWN, TX 78626 USA SN 1431-0414 BN 978-0-387-93876-9 J9 MOL BIOL INTELL UNIT JI Mol. Biol. Intell. Unit PY 2009 BP 15 EP 41 DI 10.1007/978-0-387-93877-6_2 D2 10.1007/978-0-387-93877-6 PG 27 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA BLT03 UT WOS:000270966400002 ER PT S AU Donaldson, J Segev, N AF Donaldson, Julic Segev, Nava BA Segev, N BF Segev, N TI Regulation and Coordination of Intracellular Trafficking: An Overview SO TRAFFICKING INSIDE CELLS: PATHWAYS, MECHANISMS AND REGULATION SE Molecular Biology Intelligence Unit LA English DT Article; Book Chapter ID NUCLEOTIDE-EXCHANGE FACTOR; TRANS-GOLGI; RAB GTPASES; ENDOCYTIC TRAFFICKING; COATED VESICLES; CELL-MIGRATION; YPT GTPASES; PROTEIN; YEAST; ARF AB During the last two decades, efforts in the protein trafficking field have focused primarily on the identification of the machinery components of vesicular transport and mechanisms that underlie it. In addition, research has started to reveal how intracellular trafficking is regulated. Here, we summarize the current state of our knowledge about the regulation of vesicular transport and its coordination with other cellular processes. At the most basic level, individual transport steps are regulated spatially and temporally in two different ways. First, molecular switches of the Arf, Rab and Rho GTPase families regulate the assembly of components of the vesicular transport machinery on membranes, mediating the formation, targeting and fusion of vesicles that shuttle cargo between intracellular compartments. Second, reversible posttranslational modifications, like phosphorylation and abiquitination, allow efficient cargo sorting and machinery component recycling. At a higher level, individual transport steps are integrated into whole pathways, with GTPases as a mechanism for this integration. Finally, intracellular trafficking pathways are coordinated with other cellular processes. Here too, GTPases appear to play a role by orchestrating coordination. C1 [Segev, Nava] Univ Illinois, Dept Biol Sci, Chicago, IL 60607 USA. [Donaldson, Julic] NHLBI, Cell Biol Lab, NIH, Bethesda, MD 20892 USA. RP Segev, N (reprint author), Univ Illinois, Dept Biol Sci, Chicago, IL 60607 USA. EM nava@uic.edu; nava@uic.edu NR 63 TC 4 Z9 4 U1 0 U2 1 PU LANDES BIOSCIENCE PI GEORGETOWN PA 810 S CHURCH ST, GEORGETOWN, TX 78626 USA SN 1431-0414 BN 978-0-387-93876-9 J9 MOL BIOL INTELL UNIT JI Mol. Biol. Intell. Unit PY 2009 BP 329 EP 341 DI 10.1007/978-0-387-93877-6_15 D2 10.1007/978-0-387-93877-6 PG 13 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA BLT03 UT WOS:000270966400015 ER PT J AU Singh, AK Horvath, KA Mohiuddin, MM AF Singh, A. K. Horvath, K. A. Mohiuddin, M. M. TI Rapamycin Promotes the Enrichment of CD4(+)CD25(hi)FoxP3(+) T Regulatory Cells From Naive CD4(+) T Cells of Baboon That Suppress Antiporcine Xenogenic Response In Vitro SO TRANSPLANTATION PROCEEDINGS LA English DT Article; Proceedings Paper CT 22nd International Congress of the Transplantation-Society CY AUG 10-14, 2008 CL Sydney, AUSTRALIA SP Transplantat Soc, Transplantat Soc Australia & New Zealand ID VERSUS-HOST-DISEASE; BONE-MARROW-TRANSPLANTATION AB The CD4(+)CD25(+)FoxP3(+) regulatory T (Treg) cells play an important role in regulating the immune response. These Treg cells are present in peripheral blood and lymphoid organs and have a high potential for immunotherapy in clinics. Adoptive cell transfer therapy using CD4(+)CD25(+) cells has been shown to prevent autoimmune diseases and has also induced transplant tolerance in mice. Treg cells low frequency in peripheral blood will necessitate its ex vivo expansion to enable adaptive immunotherapy. Recently, it has been reported that rapamycin, an immunosuppressive agent, inhibits T-cell proliferation while selectively increasing the number of Treg cells. Based on this additional mode of action, rapamycin can be used to expand Treg cells for ex vivo cellular therapy in T-cell-mediated diseases and in transplantation. We have reported the ex vivo expansion of baboon Treg cells, using irradiated pig peripheral blood mononuclear cell (PBMC) and interleukin (IL)-2, and have demonstrated the suppression of autologus CD4(+)CD25(neg) T-cell proliferation in response to pig PBMCs. In the present study, we have expanded baboon CD4(+) T cells in the presence or absence of rapamycin (0.1-10 nmol/L) using irradiated pig PBMCs and IL-2 to enrich the regulatory T cells. CD4(+)CD25(+)FoxP3(+) Treg cells were increased up to 2 times in the presence of rapamycin versus without rapamycin in vitro. However, a higher dose of rapamycin (>= 10 nmol/L) considerably decreases the number of Treg cells. Furthermore, purified CD4(+)CD25(+) Treg cells enriched from CD4(+) cells in the presence of rapamycin were able to suppress the baboon anti-porcine xenogeneic immune responses in vitro up to 93% at a 1:1 ratio (Treg cells:T effector cells) and suppression ability exists even at a 1:256 ratio, whereas freshly isolated natural Treg cells suppress only 70% at 1:1 and lose their suppressive ability (>50%) at 1:16. Our results demonstrate that the addition of rapamycin to the culture enriches the Treg phenotype and induces functional regulatory T cells. This method may allow the production of large numbers of regulatory cells for the preclinical testing of Treg cell therapy in a non-human primate model. C1 [Mohiuddin, M. M.] NHLBI, Cardiothorac Surg Res Program, NIH, Bethesda, MD 20850 USA. RP Mohiuddin, MM (reprint author), NHLBI, Cardiothorac Surg Res Program, NIH, 10 Ctr Dr,Bldg 10,Rm 2N246, Bethesda, MD 20850 USA. RI Mohiuddin, Muhammad/M-4642-2013 OI Mohiuddin, Muhammad/0000-0003-4654-783X FU Intramural NIH HHS [Z99 HL999999] NR 8 TC 12 Z9 14 U1 0 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0041-1345 J9 TRANSPL P JI Transplant. Proc. PD JAN-FEB PY 2009 VL 41 IS 1 BP 418 EP 421 DI 10.1016/j.transproceed.2008.10.079 PG 4 WC Immunology; Surgery; Transplantation SC Immunology; Surgery; Transplantation GA 412UG UT WOS:000263749100109 PM 19249569 ER PT S AU Newman, AH Katz, JL AF Newman, Amy Hauck Katz, Jonathan L. BE Napier, S Bingham, M TI Atypical Dopamine Uptake Inhibitors that Provide Clues About Cocaine's Mechanism at the Dopamine Transporter SO TRANSPORTERS AS TARGETS FOR DRUGS SE Topics in Medicinal Chemistry Series LA English DT Article; Book Chapter DE Addiction medication discovery; Benztropine; Cocaine; Dopamine transporter; Dopamine uptake inhibitor ID HISTAMINE H-1 ANTAGONISTS; MOLECULAR-FIELD ANALYSIS; NON-NITROGEN INHIBITORS; MONOAMINE TRANSPORTERS; RHESUS-MONKEYS; BENZTROPINE ANALOGS; IN-VIVO; 3-ALPHA-DIPHENYLMETHOXYTROPANE ANALOGS; POPULATION PHARMACOKINETICS; RIMCAZOLE ANALOGS AB The dopamine transporter (DAT) has been a primary target for cocaine abuse/adwdiction medication discovery. However predicted addiction liability and limited clinical evaluation has provided a formidable challenge for development of these agents for human use. The unique and atypical pharmacological profile of the benztropine (BZT) class of dopamine uptake inhibitors, in preclinical models of cocaine effects and abuse, has encouraged further development of these agents. Moreover, in vivo studies have challenged the original DAT hypothesis and demonstrated that DAT occupancy and subsequent increases in dopamine produced by BZT analogues are significantly delayed and long lasting, as compared to cocaine. These important and distinctive elements are critical to the lack of abuse liability among BZT analogues, and improve their potential for development as treatments for cocaine abuse and possibly other neuropsychiatric disorders. C1 [Newman, Amy Hauck; Katz, Jonathan L.] Natl Inst Drug Abuse, Medicat Discovery Res Branch, Intramural Res Program, NIH, Baltimore, MD 21224 USA. [Newman, Amy Hauck] NIDA, Med Chem Sect, IRP, NIH, Baltimore, MD 21224 USA. [Katz, Jonathan L.] NIDA, Psychobiol Sect, IRP, NIH, Baltimore, MD 21224 USA. RP Newman, AH (reprint author), Natl Inst Drug Abuse, Medicat Discovery Res Branch, Intramural Res Program, NIH, Baltimore, MD 21224 USA. EM anewman@intra.nida.nih.gov OI Katz, Jonathan/0000-0002-1068-1159 NR 78 TC 12 Z9 12 U1 2 U2 2 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013, UNITED STATES SN 1862-2461 BN 978-3-540-87911-4 J9 TOP MED CHEM SER JI Top. Med. Chem. PY 2009 VL 4 BP 95 EP 129 DI 10.1007/7355_2008_027 D2 10.1007/978-3-540-87912-1 PG 35 WC Chemistry, Medicinal SC Pharmacology & Pharmacy GA BKL76 UT WOS:000268445900004 ER PT J AU Mattson, MP Ashery, U AF Mattson, Mark P. Ashery, Uri TI No more brain tangles with Delta Np73 SO TRENDS IN BIOCHEMICAL SCIENCES LA English DT Article ID ALZHEIMERS-DISEASE; NEURONAL DIFFERENTIATION; EXCITOTOXIC INSULTS; P53; P73; NEURODEGENERATION; APOPTOSIS; SURVIVAL; MICE; BAX AB In Alzheimer's disease (AD), neurons suffer dysfunction and death associated with aberrant tau phosphorylation and subsequent neurofibrillary tangles. A new study reveals a surprising neuroprotective role for a truncated p73 isoform (Delta Np73). Aged mice with reduced Delta Np73 levels exhibit tau pathology and cognitive deficits, and Delta Np73 reduction in mice with amyloid pathology causes extensive tangle formation and neuron death. These findings provide a novel animal model of AD and a potential therapeutic role for Delta Np73 inducers. C1 [Mattson, Mark P.] NIA, Neurosci Lab, Intramural Res Program, Baltimore, MD 21224 USA. [Ashery, Uri] Tel Aviv Univ, Dept Neurobiol, George S Wise Fac Life Sci, IL-69978 Tel Aviv, Israel. RP Mattson, MP (reprint author), NIA, Neurosci Lab, Intramural Res Program, Baltimore, MD 21224 USA. EM mattsonm@grc.nia.nih.gov RI Mattson, Mark/F-6038-2012 FU Intramural NIH HHS [Z01 AG000313-07] NR 24 TC 4 Z9 4 U1 0 U2 1 PU ELSEVIER SCIENCE LONDON PI LONDON PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND SN 0968-0004 J9 TRENDS BIOCHEM SCI JI Trends Biochem.Sci. PD JAN PY 2009 VL 34 IS 1 BP 6 EP 8 DI 10.1016/j.tibs.2008.10.004 PG 3 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 402HY UT WOS:000263006000005 PM 19008105 ER PT J AU Doyle, SM Wickner, S AF Doyle, Shannon M. Wickner, Sue TI Hsp104 and ClpB: protein disaggregating machines SO TRENDS IN BIOCHEMICAL SCIENCES LA English DT Review ID PLUS CHAPERONE CLPB; SACCHAROMYCES-CEREVISIAE HSP104; TERMINAL ATPASE DOMAIN; ESCHERICHIA-COLI; MOLECULAR CHAPERONE; DEGRADATION MACHINE; SUBSTRATE RECOGNITION; AGGREGATED PROTEINS; NUCLEOTIDE-BINDING; PRION PROPAGATION AB Heat-shock protein 104 (Hsp104) and caseinolytic peptidase B (ClpB), members of the AAA+ superfamily, are molecular machines involved in disaggregating insoluble protein aggregates, a process not long ago thought to be impossible. During extreme stress they are essential for cell survival. In addition, Hsp104 regulates prion assembly and disassembly. For most of their protein remodeling activities Hsp104 and ClpB work in collaboration with the Hsp70 or DnaK chaperone systems. Together, the two chaperones catalyze protein disaggregation and reactivation by a mechanism probably involving the extraction of polypeptides from aggregates by forced unfolding and translocation through the Hsp104/ClpB central cavity. The polypeptides are then released back into the cellular milieu for spontaneous or chaperone-mediated refolding. C1 [Doyle, Shannon M.; Wickner, Sue] NCI, Mol Biol Lab, NIH, Bethesda, MD 20892 USA. RP Wickner, S (reprint author), NCI, Mol Biol Lab, NIH, Bethesda, MD 20892 USA. EM wickners@mail.nih.gov FU National Institutes of Health National Cancer Institute Center for Cancer Research FX We thank Joel Hoskins, Jodi Camberg and Danielle Johnston for their helpful discussions and critical reading of the manuscript. Work in our laboratory is supported by the Intramural Research Program of the National Institutes of Health National Cancer Institute Center for Cancer Research (http://ccr.cancer.gov). NR 81 TC 138 Z9 139 U1 4 U2 16 PU ELSEVIER SCIENCE LONDON PI LONDON PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND SN 0968-0004 J9 TRENDS BIOCHEM SCI JI Trends Biochem.Sci. PD JAN PY 2009 VL 34 IS 1 BP 40 EP 48 DI 10.1016/j.tibs.2008.09.010 PG 9 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 402HY UT WOS:000263006000010 PM 19008106 ER PT J AU Hamburg, NM Benjamin, EJ AF Hamburg, Naomi M. Benjamin, Emelia J. TI Assessment of Endothelial Function Using Digital Pulse Amplitude Tonometry SO TRENDS IN CARDIOVASCULAR MEDICINE LA English DT Review ID OXIDE-DEPENDENT VASODILATION; OBSTRUCTIVE SLEEP-APNEA; FLOW-MEDIATED DILATION; FLAVANOL-RICH COCOA; NITRIC-OXIDE; VASCULAR FUNCTION; FALCIPARUM-MALARIA; REACTIVE HYPEREMIA; DYSFUNCTION; HUMANS AB The importance of endothelial dysfunction in the development and clinical expression of cardiovascular disease is well recognized. Impaired endothelial function has been associated with an increased risk of cardiovascular events. Endothelial function may be evaluated in humans by assessing vasodilation in response to stimuli known to induce the release of nitric oxide. A novel pulse amplitude tonometry device noninvasively measures vasodilator function in the microcirculation of the finger. This article reviews the recent studies that support the utility of digital pulse amplitude tonometry as a relevant test of peripheral endothelial function. (Trends Cardiovasc Med 2009; 19:6-11) (C) 2009, Elsevier Inc. C1 [Hamburg, Naomi M.] Boston Univ, Whitaker Cardiovasc Inst, Dept Med, Sch Med, Boston, MA 02118 USA. [Benjamin, Emelia J.] Whitaker Cardiovasc Inst, Dept Med, Prevent Med Sect, Boston, MA 02118 USA. [Benjamin, Emelia J.] Boston Univ, Dept Epidemiol, Sch Publ Hlth, Boston, MA 02118 USA. [Benjamin, Emelia J.] NHLBI, Framingham, MA 01702 USA. [Benjamin, Emelia J.] Boston Univ Framingham Heart Study, Framingham, MA 01702 USA. RP Hamburg, NM (reprint author), Boston Univ, Whitaker Cardiovasc Inst, Dept Med, Sch Med, 88 E Newton St C818, Boston, MA 02118 USA. EM naomi.hamburg@bmc.org OI Benjamin, Emelia/0000-0003-4076-2336 FU National Institutes of Health [HL083781]; [RO1 HL076784]; [1R01 AG028321]; [RO1 HL70100]; [N01-HC 25195] FX Dr Hamburg is supported by National Institutes of Health grant HL083781. Dr Benjamin receives support from RO1 HL076784, 1R01 AG028321, RO1 HL70100, and N01-HC 25195. NR 32 TC 76 Z9 82 U1 1 U2 6 PU ELSEVIER SCIENCE LONDON PI LONDON PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND SN 1050-1738 J9 TRENDS CARDIOVAS MED JI Trends Cardiovasc. Med. PD JAN PY 2009 VL 19 IS 1 BP 6 EP 11 AR PII S1050-1738(09)00051-6 PG 6 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 462NQ UT WOS:000267361200002 PM 19467447 ER PT J AU Morrison, DK AF Morrison, Deborah K. TI The 14-3-3 proteins: integrators of diverse signaling cues that impact cell fate and cancer development SO TRENDS IN CELL BIOLOGY LA English DT Review ID ORGAN SIZE CONTROL; HIPPO PATHWAY; JNK PHOSPHORYLATION; CONTACT INHIBITION; GROWTH-CONTROL; GENE-PRODUCT; DNA-DAMAGE; B-RAF; MTOR; TSC2 AB The highly conserved 14-3-3 protein family has risen to a position of importance in cell biology owing to its involvement in vital cellular processes, such as metabolism, protein trafficking, signal transduction, apoptosis and cell-cycle regulation. The 14-3-3 proteins are phosphoserine/phospho-threonine binding proteins that interact with a diverse array of binding partners. Because many 14-3-3 interactions are phosphorylation-dependent, 14-3-3 has been tightly integrated into the core phosphoregulatory pathways that are crucial for normal growth and development and that often become dysregulated in human disease states such as cancer. This review examines the recent advances that further elucidate the role of 14-3-3 proteins as integrators of diverse signaling cues that influence cell fate decisions and tumorigenesis. C1 NCI Frederick, Lab Cell & Dev Signaling, Frederick, MD 21702 USA. RP Morrison, DK (reprint author), NCI Frederick, Lab Cell & Dev Signaling, Frederick, MD 21702 USA. EM dmorrison@nciferf.gov FU Intramural NIH HHS [ZIA BC010329-11] NR 66 TC 293 Z9 306 U1 4 U2 39 PU ELSEVIER SCIENCE LONDON PI LONDON PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND SN 0962-8924 J9 TRENDS CELL BIOL JI Trends Cell Biol. PD JAN PY 2009 VL 19 IS 1 BP 16 EP 23 DI 10.1016/j.tcb.2008.10.003 PG 8 WC Cell Biology SC Cell Biology GA 402HP UT WOS:000263005100003 PM 19027299 ER PT J AU Kunos, G Osei-Hyiaman, D Batkai, S Sharkey, KA Makriyannis, A AF Kunos, George Osei-Hyiaman, Douglas Batkai, Sandor Sharkey, Keith A. Makriyannis, Alexandros TI Should peripheral CB1 cannabinoid receptors be selectively targeted for therapeutic gain? SO TRENDS IN PHARMACOLOGICAL SCIENCES LA English DT Review ID DIET-INDUCED OBESITY; ENDOCANNABINOID SYSTEM; ANTAGONIST SR141716; INSULIN-RESISTANCE; NEUROPATHIC PAIN; ENERGY-BALANCE; RISK-FACTORS; OVERWEIGHT PATIENTS; METABOLIC SYNDROME; LEPTIN RESISTANCE AB Endocannabinoids, endogenous lipid ligands of cannabinoid receptors, mediate a variety of effects similar to those of marijuana. Cannabinoid CB1 receptors are highly abundant in the brain and mediate psychotropic effects, which limits their value as a potential therapeutic target. There is growing evidence for CB1 receptors in peripheral tissues that modulate a variety of functions, including pain sensitivity and obesity-related hormonal and metabolic abnormalities. In this review we propose that selective targeting of peripheral CB1 receptors has potential therapeutic value because it would help to minimize addictive, psychoactive effects in the case of CB1 agonists used as analgesics, or depression and anxiety in the case of CB1 antagonists used in the management of cardiometabolic risk factors associated with the metabolic syndrome. C1 [Kunos, George; Osei-Hyiaman, Douglas; Batkai, Sandor] NIAAA, Lab Physiol Studies, Bethesda, MD 20892 USA. [Sharkey, Keith A.] Univ Calgary, Hotchkiss Brain Inst, Calgary, AB T2N 4N1, Canada. [Makriyannis, Alexandros] Northeastern Univ, Ctr Drug Discovery, Boston, MA 02115 USA. RP Kunos, G (reprint author), NIAAA, Lab Physiol Studies, Bethesda, MD 20892 USA. EM gkunos@mail.nih.gov RI Batkai, Sandor/G-3889-2010; Batkai, Sandor/H-7983-2014 FU National Institutes of Health FX The work of G.K., D. O-H. and S.B. is supported by intramural funds of the National Institutes of Health. NR 65 TC 74 Z9 76 U1 1 U2 5 PU ELSEVIER SCIENCE LONDON PI LONDON PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND SN 0165-6147 J9 TRENDS PHARMACOL SCI JI Trends Pharmacol. Sci. PD JAN PY 2009 VL 30 IS 1 BP 1 EP 7 DI 10.1016/j.tips.2008.10.001 PG 7 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 400VY UT WOS:000262898700001 PM 19042036 ER PT J AU O'Meara, WP Noor, A Gatakaa, H Tsofa, B McKenzie, FE Marsh, K AF O'Meara, W. P. Noor, A. Gatakaa, H. Tsofa, B. McKenzie, F. E. Marsh, K. TI The impact of primary health care on malaria morbidity - defining access by disease burden SO TROPICAL MEDICINE & INTERNATIONAL HEALTH LA English DT Article DE primary health care; malaria morbidity; access; travel time; Kenya ID KENYA; CHILDREN; SERVICES; COAST; TRANSMISSION; VACCINE; EQUITY; FEVERS AB Primary care facilities are increasingly becoming the focal point for distribution of malaria intervention strategies, but physical access to these facilities may limit the extent to which communities can be reached. To investigate the impact of travel time to primary care on the incidence of hospitalized malaria episodes in a rural district in Kenya. The incidence of hospitalized malaria in a population under continuous demographic surveillance was recorded over 3 years. The time to travel to the nearest primary health care facility was calculated for every child between birth and 5 years of age and trends in incidence of hospitalized malaria as a function of travel time were evaluated. The incidence of hospitalized malaria more than doubled as travel time to the nearest primary care facility increased from 10 min to 2 h. Good access to primary health facilities may reduce the burden of disease by as much as 66%. Our results highlight both the potential of the primary health care system in reaching those most at risk and reducing the disease burden. Insufficient access is an important risk factor, one that may be inequitably distributed to the poorest households. C1 [O'Meara, W. P.; McKenzie, F. E.] NIH, Fogarty Int Ctr, Bethesda, MD 20892 USA. [Noor, A.] Wellcome Trust Collaborat Program, KEMRI, Nairobi, Kenya. [Gatakaa, H.] Kenya Govt Med Res Ctr, CGMRC, Wellcome Trust Collaborat Program, Kilifi, Kenya. [Tsofa, B.; Marsh, K.] Minist Hlth, Kilifi, Kenya. RP O'Meara, WP (reprint author), NIH, Fogarty Int Ctr, Bldg 10, Bethesda, MD 20892 USA. EM prudhomw@mail.nih.gov FU Fogarty International Center of the National Institutes of Health; The Wellcome Trust; Kenya Medical Research Institute FX WPO gratefully acknowledges the Fogarty International Center of the National Institutes of Health for funding and support. This investigation received financial support from The Wellcome Trust and the Kenya Medical Research Institute. NR 24 TC 24 Z9 24 U1 0 U2 2 PU WILEY-BLACKWELL PUBLISHING, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1360-2276 J9 TROP MED INT HEALTH JI Trop. Med. Int. Health PD JAN PY 2009 VL 14 IS 1 BP 29 EP 35 DI 10.1111/j.1365-3156.2008.02194.x PG 7 WC Public, Environmental & Occupational Health; Tropical Medicine SC Public, Environmental & Occupational Health; Tropical Medicine GA 395IN UT WOS:000262517900005 PM 19121148 ER PT J AU Bermudez-Morales, VH Peralta-Zaragoza, O Guzman-Olea, E Garcia-Carranca, A Bahena-Roman, M Alcocer-Gonzalez, JM Madrid-Marina, V AF Bermudez-Morales, V. H. Peralta-Zaragoza, O. Guzman-Olea, E. Garcia-Carranca, A. Bahena-Roman, M. Alcocer-Gonzalez, J. M. Madrid-Marina, V. TI HPV 16 E2 Protein Induces Apoptosis in Human and Murine HPV 16 Transformed Epithelial Cells and Has Antitumoral Effects in vivo SO TUMOR BIOLOGY LA English DT Article DE HPV 16 E2; Apoptosis; Cell death; Epithelial cells ID HUMAN-PAPILLOMAVIRUS TYPE-16; CERVICAL-CARCINOMA CELLS; BOVINE PAPILLOMAVIRUS; REGULATORY REGION; DNA IMMUNIZATION; PHYSICAL STATUS; VACCINIA VIRUS; HELA-CELLS; HIGH-RISK; GENE AB Objective: Our aims were to examine the ability of the human papillomaviruse (HPV) 16 E2 protein to induce apoptosis in a murine HPV-transformed cell line, and to evaluate its antitumor properties on HPV-associated tumors in vivo in immunocompetent mice. Methods: HPV-transformed murine BMK-16/myc cells and human SiHa cells were transfected with the HPV 16 E2 gene to examine the effects of the E2 protein on cell growth and on the E6 and E7 oncogenes as well as DNA fragmentation and activation of the extrinsic pathway of apoptosis. Finally, to test the antitumor effect of the E2 protein on an experimental mouse tumor model, we generated a recombinant adenovirus expressing the E2 protein. Results: The E2 protein inhibited the growth of SiHa and BMK-16/myc cell lines, and repressed the E6 and E7 oncogenes. Moreover, the E2 protein induced DNA fragmentation and apoptosis through activation of caspases 8 and 3 in BMK-16/myc cells. On the other hand, E2 also showed antitumor effects in vivo. Conclusions: Our findings indicate that E2 exerts pro-apoptotic activity in a murine HPV-transformed cell line as well as an antitumor effect in vivo. Copyright (C) 2009 S. Karger AG, Basel C1 [Bermudez-Morales, V. H.; Peralta-Zaragoza, O.; Bahena-Roman, M.; Madrid-Marina, V.] Natl Inst Publ Hlth, Cuernavaca 62508, Morelos, Mexico. [Guzman-Olea, E.] Natl Canc Inst, Biomed Res Inst, Unit Biomed Res Canc, Bethesda, MD 20892 USA. [Bermudez-Morales, V. H.] Univ Nacl Autonoma Mexico, Sch Med, Mexico City 04510, DF, Mexico. [Alcocer-Gonzalez, J. M.] Autonomous Univ Nuevo Leon, Sch Biol Sci, Monterrey, Mexico. RP Madrid-Marina, V (reprint author), Natl Inst Publ Hlth, Av Univ 655, Cuernavaca 62508, Morelos, Mexico. EM vmarina@correo.insp.mx FU CONACYT [125098]; Mexican government through a grant from CONACYT-SEP [46151]; Universidad Nacional Autonoma de Mexico [501036762] FX This work was submitted in partial fulfillment of the requirements for the DSc degree by Victor Hugo Bermudez-Morales at the Doctorado en Ciencias Biomedicas, Universidad Nacional Autonoma de Mexico. Number: 501036762. NR 48 TC 5 Z9 8 U1 0 U2 2 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 1010-4283 J9 TUMOR BIOL JI Tumor Biol. PY 2009 VL 30 IS 2 BP 61 EP 72 DI 10.1159/000214438 PG 12 WC Oncology SC Oncology GA 446CM UT WOS:000266098000002 PM 19390235 ER PT S AU Weissman, AM Yang, Y Kitagaki, J Sasiela, CA Beutler, JA O'Keefe, BR AF Weissman, A. M. Yang, Y. Kitagaki, J. Sasiela, C. A. Beutler, J. A. O'Keefe, B. R. BE Jentsch, S Haendler, B TI Inhibiting Hdm2 and Ubiquitin-Activating Enzyme: Targeting the Ubiquitin Conjugating System in Cancer SO Ubiquitin System in Health and Disease SE Ernst Schering Foundation Symposium Proceedings LA English DT Proceedings Paper CT Ernst-Schering-Foundation Symposium on Ubiquitin System in Health and Disease CY APR 09-11, 2008 CL Berlin, GERMANY SP Ernst Schering Fdn ID LIGASE ACTIVITY; P53 PATHWAY; MDM2; PROTEINS; CELLS; BORTEZOMIB; MECHANISM; SCREEN; ITSELF; GENE AB The ubiquitin conjugating system represents a rich source of potential molecular targets for cancer and other diseases. One target of great interest is the RING finger ubiquitin ligase (B) Hdm2/Mdm2, which is frequently overexpressed in cancer and is a critical E3 for the tumor suppressor p53. For those 50% of tumors that express wild-type p53, agents that inhibit Hdm2 have great potential clinical utility. We summarize our ongoing efforts to identify inhibitors of Hdm2 E3 activity by high-throughput screening of both defined small molecules and natural product extracts. Employing a strategy using both enzymatic and cell-based assays, we have identified inhibitors that block the E3 activity of Hdm2, activate a p53 response, preferentially kill p53-expressing cells, and have the capacity to differentially cause death of transformed cells. Therefore, screening for inhibitors of Hdm2 ubiquitin ligase activity through in vitro assays represents a powerful means of identifying molecules that activate p53 in cancer cells to induce apoptosis. We also discuss the potential of inhibitors Of Ubiquitin-activating enzyme (El) that were discovered during these screens. El inhibitors may similarly serve its the basis for novel therapeutics. Additionally, they represent unique tools for providing new insights into the ubiquitin conjugating system. C1 [Weissman, A. M.; Yang, Y.; Kitagaki, J.; Sasiela, C. A.; Beutler, J. A.; O'Keefe, B. R.] NCI, Lab Prot Dynam & Signaling, Frederick, MD 21702 USA. RP Weissman, AM (reprint author), NCI, Lab Prot Dynam & Signaling, Rm 22-103,POB Bldg 560, Frederick, MD 21702 USA. EM amw@nih.gov NR 40 TC 0 Z9 0 U1 0 U2 3 PU SPRINGER-VERLAG BERLIN PI BERLIN PA HEIDELBERGER PLATZ 3, D-14197 BERLIN, GERMANY SN 0947-6075 BN 978-3-540-85106-6 J9 ERNST SCHERING FOUND PY 2009 VL 1 BP 171 EP 190 DI 10.1007/2789_2008_108 PG 20 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA BIS93 UT WOS:000262475400011 ER PT B AU Jakobsson, E AF Jakobsson, Eric BE Cope, B Kalantzis, M TI Biology Using a Ubiquitous Knowledge Environment to Integrate Teaching, Learning, and Research in Biology and Chemistry SO UBIQUITOUS LEARNING LA English DT Article; Book Chapter ID EVOLUTION; DATABASE C1 [Jakobsson, Eric] Univ Illinois, Dept Mol & Integrat Physiol, Urbana, IL 61801 USA. [Jakobsson, Eric] Univ Illinois, Natl Ctr Supercomp Applicat, Urbana, IL 61801 USA. [Jakobsson, Eric] NIH, Biomed Informat Sci & Technol Initiat Consortium, Bethesda, MD 20892 USA. [Jakobsson, Eric] NIH, Natl Ctr Design Biomimet Nanoconductors, Bethesda, MD 20892 USA. [Jakobsson, Eric] Amer Phys Soc, College Pk, MD USA. RP Jakobsson, E (reprint author), Univ Illinois, Dept Mol & Integrat Physiol, Urbana, IL 61801 USA. NR 17 TC 0 Z9 0 U1 0 U2 0 PU UNIV ILLINOIS PRESS PI URBANA PA URBANA, IL 61801 USA BN 978-0-252-07680-0 PY 2009 BP 216 EP 229 PG 14 WC Education & Educational Research SC Education & Educational Research GA BCI38 UT WOS:000310243800020 ER PT J AU Kagiya, G Ogawa, R Ito, S Fukuda, S Hatashita, M Tanaka, Y Yamamoto, K Kondo, T AF Kagiya, Go Ogawa, Ryohei Ito, Shinji Fukuda, Shigekazu Hatashita, Masanori Tanaka, Yoshikazu Yamamoto, Kazutaka Kondo, Takashi TI IDENTIFICATION OF A CIS-ACTING ELEMENT RESPONSIVE TO ULTRASOUND IN THE 5 '-FLANKING REGION OF THE HUMAN HEME OXYGENASE-1 GENE SO ULTRASOUND IN MEDICINE AND BIOLOGY LA English DT Article DE Ultrasound; Heme oxygenase-1; Reactive oxygen species; Stress-responsive element ID TRANSCRIPTIONAL ACTIVATION; NITRIC-OXIDE; CELLS; EXPRESSION; INDUCTION; CADMIUM; MECHANISM; NRF2; SONOCHEMISTRY; ARSENITE AB We previously found that the heme oxygenase-1 gene (hmox-1) was the most upregulated gene among 9,182 genes in human lymphoma U937 cells exposed to 1-MHz continuous ultrasound using the cDNA microarray technique. However, little is known about the molecular mechanisms of the induction of hmox-1 expression by ultrasound. We investigated the mechanism using human prostate cancer DU145 cells in which expression of hmox-1 increased with sonication in a time and an intensity-dependent manner. When N-acetyl-L-cysteine or glutathione-monoethyl ester, a potent antioxidant, was added to cell culture, hmox-1 upregulation was attenuated, suggesting that oxidative stress caused by sonication is involved in this process. To identify cis-acting elements required for the ultrasound-mediated induction, we carried out transient expression assays with plasmids carrying the luciferase gene under control of deletion mutants of the 5'-flanking region of hmox-1. The results revealed that the upregulations by sonication were observed with deletion mutants carrying the El or E2 enhancer of the 5'-flanking region, suggesting stress-responsive elements (StRE) were involved in the induction because either enhancer contains a number of the element. Indeed, site-directed mutations within StRE decreased the reactivity of deletion mutants to sonication. A transcription factor NF-E2-related Factor 2 that binds to StRE would therefore be activated by oxidative stress induced by sonication. C1 [Ogawa, Ryohei; Kondo, Takashi] Toyama Univ, Grad Sch Med & Pharmaceut Sci, Dept Radiol Sci, Toyama 9300194, Japan. [Kagiya, Go; Ito, Shinji] NCI, Radiat Biol Branch, NIH, Bethesda, MD 20892 USA. [Kagiya, Go] Kitasato Univ, Sch Allied Hlth Sci, Kanagawa, Japan. [Fukuda, Shigekazu; Yamamoto, Kazutaka] Wakasa Wan Energy Res Ctr, Div Med, Fukui, Japan. [Hatashita, Masanori; Tanaka, Yoshikazu] Wakasa Wan Energy Res Ctr, Biol Grp, Fukui, Japan. RP Ogawa, R (reprint author), Toyama Univ, Grad Sch Med & Pharmaceut Sci, Dept Radiol Sci, Toyama 9300194, Japan. EM ogawa@med.u-toyama.ac.jp NR 30 TC 6 Z9 6 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0301-5629 J9 ULTRASOUND MED BIOL JI Ultrasound Med. Biol. PD JAN PY 2009 VL 35 IS 1 BP 155 EP 164 DI 10.1016/j.ultrasmedbio.2008.07.012 PG 10 WC Acoustics; Radiology, Nuclear Medicine & Medical Imaging SC Acoustics; Radiology, Nuclear Medicine & Medical Imaging GA 390DN UT WOS:000262144600019 PM 18829152 ER PT J AU Vaughn, DW Whitehead, SS Durbin, AP AF Vaughn, David W. Whitehead, Stephen S. Durbin, Anna P. BE Barrett, ADT Stanberry, LR TI Dengue SO VACCINES FOR BIODEFENSE AND EMERGING AND NEGLECTED DISEASES LA English DT Article; Book Chapter ID T-CELL RESPONSES; NEUTRALIZING ANTIBODY-RESPONSE; RECOMBINANT VACCINIA VIRUS; HUMAN ENDOTHELIAL-CELLS; DISSEMINATED INTRAVASCULAR COAGULATION; CLINICAL LABORATORY RESPONSES; RESPIRATORY SYNCYTIAL VIRUS; JAPANESE-ENCEPHALITIS-VIRUS; PERIPHERAL-BLOOD LEUKOCYTES; INTERFERON GAMMA-PRODUCTION AB Molecular evolution studies suggest that dengue virus (DENV) evolved 1000 years ago and entered a sustained human-mosquito cycle between 125 and 320 years ago. While it is unlikely that DENV would be used as a biothreat agent, DENV has emerged since World War II as the most important mosquito-borne viral pathogen infecting an estimated 100 million persons each year. Infection with any of the four DENV serotypes (DENV-1, 2, 3, and 4) can be inapparent, result in classic dengue fever with high fever, headache, eye pain and muscle ache, or progress at the time of defervescence to dengue hemorrhagic fever (DHF) characterized by hemorrhagic manifestations and plasma leakage that can lead to shock and death. The immunopathological mechanisms by which DENV causes the clinical features of DHF are intricate and include aberrant humoral and cellular immune responses. Previous DENV infections may predispose to more severe disease by the induction of enhancing antibody and cross-reactive T cells. Treatment is supportive relying upon careful fluid management which can be lifesaving. Prevention currently depends on vector control which has been largely unsuccessful. Several dengue vaccine candidates have advanced to clinical trials to include classically and molecularly attenuated live virus vaccines, chimeric vaccines using dengue and yellow fever virus backbones, and DNA vaccines. Whole virus inactivated and recombinant subunit vaccine candidates should soon enter into clinical testing. Live attenuated DENV vaccines offer the most promise in terms of broad, long-lasting protection, and although they are economical to produce, they may carry the risks of enhanced reactogenicity in recipients with preexisting flavivirus antibodies, adverse events among the immunocompromised, vaccine virus transmission by vector mosquitoes, and the risk of adventitious agents. Chimeric vaccine approaches use the same gene sequence for the nonstructural proteins for each of the four DENV serotypes avoiding the need for attenuating mutations in the structural genes and potentially reducing interference in the replication of the four virus vaccine components within the multivalent vaccine recipient. DNA vaccines, in combination with other approaches, may increase the complexity and effectiveness of the immune response. Whole inactivated virus approaches have been used successfully for other viral diseases, reduce interference issues in multivalent vaccines, and have protected nonhuman primates from viremia following challenge with wild-type virus. Recombinant subunit vaccines have also protected nonhuman primates from viremia and offer a more focused approach in an attempt to tailor antibody and cell-mediated immure responses. While pathogenesis studies seek to dissect immune responses in an attempt to avoid vaccine-related disease enhancement, these risks, which apply to all vaccine approaches, may need to be evaluated empirically. C1 [Vaughn, David W.] USA, Mil Infect Dis Res Program, Med Res & Dev Command, Ft Detrick, MD USA. [Whitehead, Stephen S.] NIAID, Infect Dis Lab, Bethesda, MD 20892 USA. [Durbin, Anna P.] Johns Hopkins Bloomberg Sch Publ Hlth, Ctr Immunizat Res, Dept Int Hlth, Baltimore, MD USA. RP Vaughn, DW (reprint author), USA, Mil Infect Dis Res Program, Med Res & Dev Command, Ft Detrick, MD USA. NR 356 TC 1 Z9 1 U1 1 U2 3 PU ELSEVIER ACADEMIC PRESS INC PI SAN DIEGO PA 525 B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 USA BN 978-0-08-091902-7 PY 2009 BP 287 EP 324 PG 38 WC Public, Environmental & Occupational Health; Immunology; Infectious Diseases SC Public, Environmental & Occupational Health; Immunology; Infectious Diseases GA BCR60 UT WOS:000311106000021 ER PT S AU Chen, GL Subbarao, K AF Chen, Grace L. Subbarao, Kanta BE Compans, RW Orenstein, WA TI Live Attenuated Vaccines for Pandemic Influenza SO VACCINES FOR PANDEMIC INFLUENZA SE Current Topics in Microbiology and Immunology LA English DT Article; Book Chapter DE live attenuated influenza vaccines pandemic; Plasmid-based reverse genetics techniques ID COLD-ADAPTED INFLUENZA; A VIRUS-VACCINES; RANDOMIZED CONTROLLED-TRIAL; YOUNG-CHILDREN; HONG-KONG; TEMPERATURE SENSITIVITY; INACTIVATED VACCINES; GENOTYPIC STABILITY; ANTIBODY-RESPONSES; REVERSE GENETICS AB In this chapter, we will review the development of and clinical experience with the currently licensed seasonal live attenuated influenza vaccines (LAIV) and preclinical studies of H5, H7, and H9 live attenuated pandemic influenza vaccine candidates. Vectored vaccine approaches will not be reviewed in this chapter. Experience with seasonal influenza vaccination has demonstrated the safety and efficacy of LAIV in both children and adults; moreover, cross-protection among antigenically distinct viruses within the same subtype may be induced by LAIV. While clinical studies and further characterization of the immunologic response to avian influenza viruses are still needed, the experience with seasonal LAIV underscores the potential of live attenuated vaccines to play an important role in the event of a pandemic. C1 [Subbarao, Kanta] NIAID, Infect Dis Lab, NIH, Bethesda, MD 20892 USA. RP Subbarao, K (reprint author), NIAID, Infect Dis Lab, NIH, Bldg 33,Room 3E13C-1,33 N Dr,MSC 3203, Bethesda, MD 20892 USA. EM chengra@niaid.nih.gov; ksubbarao@niaid.nih.gov FU Intramural NIH HHS NR 82 TC 16 Z9 17 U1 0 U2 3 PU SPRINGER-VERLAG BERLIN PI BERLIN PA HEIDELBERGER PLATZ 3, D-14197 BERLIN, GERMANY SN 0070-217X BN 978-3-540-92164-6 J9 CURR TOP MICROBIOL JI Curr.Top.Microbiol.Immunol. PY 2009 VL 333 BP 109 EP 132 DI 10.1007/978-3-540-92165-3_5 D2 10.1007/978-3-540-92165-3 PG 24 WC Biotechnology & Applied Microbiology; Immunology; Microbiology SC Biotechnology & Applied Microbiology; Immunology; Microbiology GA BKY26 UT WOS:000269608300005 PM 19768402 ER PT J AU Jefferson, AL Benjamin, EJ AF Jefferson, Angela L. Benjamin, Emelia J. BE Wahlund, LO Erkinjuntti, T Gauthier, S TI Cardiovascular disease, cognitive decline, and dementia SO VASCULAR COGNITIVE IMPAIRMENT IN CLINICAL PRACTICE LA English DT Article; Book Chapter ID VASCULAR RISK-FACTORS; ARTERY-BYPASS GRAFT; INCIDENT ALZHEIMER-DISEASE; NONVALVULAR ATRIAL-FIBRILLATION; LEFT-VENTRICULAR DYSFUNCTION; HOSPITAL CARDIAC-ARREST; CEREBRAL BLOOD-FLOW; HEART-FAILURE; APOLIPOPROTEIN-E; MYOCARDIAL-INFARCTION C1 [Jefferson, Angela L.] Boston Univ, Sch Med, Dept Neurol, Boston, MA 02118 USA. [Jefferson, Angela L.] Boston Univ, Sch Med, Alzheimers Dis Ctr, Boston, MA 02118 USA. [Benjamin, Emelia J.] NHLBI, Framingham Heart Study, Framingham, MA USA. [Benjamin, Emelia J.] Boston Univ, Sch Med, Dept Prevent Med, Boston, MA 02118 USA. [Benjamin, Emelia J.] Boston Univ, Sch Med, Whitaker Cardiovasc Inst, Boston, MA 02118 USA. [Benjamin, Emelia J.] Boston Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA USA. RP Jefferson, AL (reprint author), Boston Univ, Sch Med, Dept Neurol, Boston, MA 02118 USA. OI Benjamin, Emelia/0000-0003-4076-2336 NR 80 TC 2 Z9 2 U1 0 U2 0 PU CAMBRIDGE UNIV PRESS PI CAMBRIDGE PA THE PITT BUILDING, TRUMPINGTON ST, CAMBRIDGE CB2 1RP, CAMBS, ENGLAND BN 978-0-521-87537-0 PY 2009 BP 166 EP 177 DI 10.1017/CBO9780511575976.014 D2 10.1017/CBO9780511575976 PG 12 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA BDM65 UT WOS:000313873000014 ER PT J AU Reynolds, TL Barnes, HJ Wolfe, B Lu, L Camp, DM Malarkey, DE AF Reynolds, T. L. Barnes, H. J. Wolfe, B. Lu, L. Camp, D. M. Malarkey, D. E. TI Bilateral Nocardial Endophthalmitis in a Prothonotary Warbler (Protonotaria citrea) SO VETERINARY PATHOLOGY LA English DT Article DE Acid-fast stain; avian; eye; Fite's acid-fast stain; Nocardia; Passeriformes; prothonotary warbler; Protonotaria citrea; pyogranulomatous endophthalmitis AB A 7-year-old captive female prothonotary warbler (Protonotaria citrea) died following chronic feather and weight loss. At necropsy, the right eye had a 2 x 2 x 1 mm corneal plaque Of inspissated yellow-tan material and edema of the lower eyelid. Microscopically, both eyes exhibited diffuse, severe pyogranulomatous endophthalmitis with retinal necrosis and detachment. Numerous intralesional branching, gram-positive. beaded, filamentous bacteria formed a thick mat attached to the retinal pigmented epithelium and extending into the pecten. Bacteria were strongly acid-fast positive by Fite's stain but only occasionally acid-fast positive by Ziehl-Neelsen staining, a characteristic consistent with a Nocardia spp. Infected regions demonstrated positive In situ hybridization reactivity with a probe complementary to the 16S rRNA gene of Nocardia spp. There was no evidence of primary bacterial infection in the other organs examined. C1 [Malarkey, D. E.] NIEHS, Natl Toxicol Program, Pathol Grp, Cellular & Mol Pathol Branch, Res Triangle Pk, NC 27709 USA. [Reynolds, T. L.] Johns Hopkins Univ, Sch Med, Dept Pathol, Baltimore, MD 21205 USA. [Barnes, H. J.] N Carolina State Univ, Coll Vet Med, Dept Populat Hlth & Pathobiol, Raleigh, NC USA. [Wolfe, B.] Hanes Vet Med Ctr, Asheboro, NC USA. [Lu, L.] RFU, Sch Med, N Chicago, IL USA. [Camp, D. M.] William Beaumont Hosp, Res Inst, Royal Oak, MI 48072 USA. RP Malarkey, DE (reprint author), NIEHS, Natl Toxicol Program, Pathol Grp, Cellular & Mol Pathol Branch, 111 Alexander Dr,Maildrop B3-O6,POB 12233, Res Triangle Pk, NC 27709 USA. EM malarkey@niehs.nih FU Intramural NIH HHS [Z99 ES999999] NR 16 TC 0 Z9 0 U1 0 U2 0 PU AMER COLL VET PATHOLOGIST PI LAWRENCE PA 810 EAST 10TH STREET, LAWRENCE, KS 66044 USA SN 0300-9858 J9 VET PATHOL JI Vet. Pathol. PD JAN PY 2009 VL 46 IS 1 BP 120 EP 123 PG 4 WC Pathology; Veterinary Sciences SC Pathology; Veterinary Sciences GA 392UD UT WOS:000262326800018 PM 19112125 ER PT B AU Paul, AV Belov, GA Ehrenfeld, E Wimmer, E AF Paul, Aniko V. Belov, George A. Ehrenfeld, Ellie Wimmer, Eckard BE Cameron, CE Gotte, M Raney, KD TI Model of Picornavirus RNA Replication SO VIRAL GENOME REPLICATION LA English DT Article; Book Chapter ID POLY(RC) BINDING-PROTEIN; HUMAN RHINOVIRUS TYPE-14; RIBOSOMAL ENTRY SITE; MOUTH-DISEASE VIRUS; POLIOVIRUS RNA; VPG URIDYLYLATION; NEGATIVE-STRAND; VIRAL REPLICATION; ELEMENT CRE; IN-VITRO C1 [Paul, Aniko V.] SUNY Stony Brook, Dept Mol Genet & Microbiol, Stony Brook, NY 11794 USA. [Belov, George A.; Ehrenfeld, Ellie] NIAID, Picornavirus Replicat Sect, Infect Dis Lab, NIH, Bethesda, MD 20892 USA. RP Paul, AV (reprint author), SUNY Stony Brook, Dept Mol Genet & Microbiol, Nicolls Rd, Stony Brook, NY 11794 USA. EM apaul@notes.cc.sunysb.edu; gbelov@niaid.nih.gov; eehrenfeld@niaid.nih.gov; ewim-mer@ms.cc.sunysb.edu RI Belov, George/B-4625-2008 OI Belov, George/0000-0002-0892-1731 NR 59 TC 4 Z9 4 U1 1 U2 2 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013, UNITED STATES BN 978-0-387-89425-6 PY 2009 BP 3 EP 23 DI 10.1007/b135974_1 D2 10.1007/b135974 PG 21 WC Biotechnology & Applied Microbiology; Cell Biology; Immunology; Microbiology; Virology SC Biotechnology & Applied Microbiology; Cell Biology; Immunology; Microbiology; Virology GA BKY23 UT WOS:000269607500001 ER PT B AU McDonald, SM Patton, JT AF McDonald, Sarah M. Patton, John T. BE Cameron, CE Gotte, M Raney, KD TI Core-Associated Genome Replication Mechanisms of dsRNA Viruses SO VIRAL GENOME REPLICATION LA English DT Article; Book Chapter ID DOUBLE-STRANDED-RNA; ROTAVIRUS MESSENGER-RNA; L-A-VIRUS; CYTOPLASMIC POLYHEDROSIS-VIRUS; POL FUSION PROTEIN; RICE-DWARF-VIRUS; CRYOELECTRON MICROSCOPY; ELECTRON CRYOMICROSCOPY; 3-DIMENSIONAL STRUCTURE; ASSEMBLY PATHWAY C1 [Patton, John T.] NIAID, Infect Dis Lab, NIH, Bethesda, MD 20892 USA. [McDonald, Sarah M.] NIAID, Dept Lab Infect Dis, NIH, Bethesda, MD 20892 USA. RP McDonald, SM (reprint author), NIAID, Dept Lab Infect Dis, NIH, Bethesda, MD 20892 USA. EM mcdonaldsa@niaid.nih.gov; jpatton@niaid.nih.gov RI Patton, John/P-1390-2014 NR 83 TC 3 Z9 3 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013, UNITED STATES BN 978-0-387-89425-6 PY 2009 BP 201 EP 224 DI 10.1007/b135974_11 D2 10.1007/b135974 PG 24 WC Biotechnology & Applied Microbiology; Cell Biology; Immunology; Microbiology; Virology SC Biotechnology & Applied Microbiology; Cell Biology; Immunology; Microbiology; Virology GA BKY23 UT WOS:000269607500011 ER PT B AU Wendeler, M Miller, JT Le Grice, SFJ AF Wendeler, Michaela Miller, Jennifer T. Le Grice, Stuart F. J. BE Cameron, CE Gotte, M Raney, KD TI Human Immunodeficiency Virus Reverse Transcriptase SO VIRAL GENOME REPLICATION LA English DT Article; Book Chapter ID CENTRAL DNA FLAP; TYPE-1 POLYPURINE TRACT; RNASE-H CLEAVAGE; PRIMER ACTIVATION SIGNAL; INFECTIOUS-ANEMIA VIRUS; NUCLEOSIDE ANALOG INTERFERENCE; TRYPTOPHAN-REPEAT MOTIF; UNNATURAL AMINO-ACIDS; DOUBLE-STRANDED DNA; PLUS-STRAND C1 [Wendeler, Michaela; Miller, Jennifer T.; Le Grice, Stuart F. J.] NCI, HIV Drug Resistance Program, Frederick, MD 21702 USA. RP Le Grice, SFJ (reprint author), NCI, HIV Drug Resistance Program, Bldg 535,Room 312,POB B, Frederick, MD 21702 USA. EM mwendeler@ncifcrf.gov; jtmiller@ncifcrf.gov; slegrice@ncifcrf.gov NR 195 TC 1 Z9 2 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013, UNITED STATES BN 978-0-387-89425-6 PY 2009 BP 403 EP 427 DI 10.1007/b135974_19 D2 10.1007/b135974 PG 25 WC Biotechnology & Applied Microbiology; Cell Biology; Immunology; Microbiology; Virology SC Biotechnology & Applied Microbiology; Cell Biology; Immunology; Microbiology; Virology GA BKY23 UT WOS:000269607500019 ER PT J AU Cui, J Wilke, M Logothetis, NK Leopold, DA Liang, HL AF Cui, Jie Wilke, Melanie Logothetis, Nikos K. Leopold, David A. Liang, Hualou TI Visibility states modulate microsaccade rate and direction SO VISION RESEARCH LA English DT Article DE Microsaccade; Generalized flash suppression; Multistable perception; Fixation; Visual attention ID FIXATIONAL EYE-MOVEMENTS; PRIMARY VISUAL-CORTEX; COVERT ATTENTION; BINOCULAR-RIVALRY; INHIBITION; SUPPRESSION; NEURONS; INDEX; PROLONGATION; ORIENTATION AB We investigated how the perceptual visibility of a target influences the pattern of microsaccadic eye movements expressed during generalized flash suppression. We found that the microsaccade rate was highly dependent on the reported visibility of the target. In the visible trials, the microsaccade rate promptly rebounded to the pre-onset level, whereas on the invisible trials the rate remained low, reaching pre-onset levels hundreds of milliseconds later. In addition, the directional distributions of microsaccades were biased to the target positions in the visible condition. The present findings indicate that the microsaccade behavior is highly correlated with the perceptual state of target visibility, and suggest that the measured microsaccade rate and direction are reliable indicators of the perception. (C) 2008 Elsevier Ltd. All rights reserved. C1 [Cui, Jie; Liang, Hualou] Univ Texas Houston, Sch Hlth Informat Sci, Houston, TX 77030 USA. [Wilke, Melanie; Leopold, David A.] NIMH, UCNI, Bethesda, MD 20892 USA. [Logothetis, Nikos K.] Max Planck Inst Biol Cybernet, D-72076 Tubingen, Germany. RP Liang, HL (reprint author), Univ Texas Houston, Sch Hlth Informat Sci, Houston, TX 77030 USA. EM Hualou.Liang@uth.tmc.edu OI Leopold, David/0000-0002-1345-6360 FU NIH [R01 MH072034]; Max Planck Society; NSERC postdoctoral fellowship FX We thank Dr. Igor Kagan for helpful discussions. This work was supported by NIH Grant R01 MH072034 (H.L.), Max Planck Society, and partially by a NSERC postdoctoral fellowship (J.C.). NR 48 TC 35 Z9 35 U1 1 U2 9 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0042-6989 J9 VISION RES JI Vision Res. PD JAN PY 2009 VL 49 IS 2 BP 228 EP 236 DI 10.1016/j.visres.2008.10.015 PG 9 WC Neurosciences; Ophthalmology SC Neurosciences & Neurology; Ophthalmology GA 396QK UT WOS:000262606000007 PM 19007803 ER PT S AU Jian, B Vemuri, BC Ozarslan, E AF Jian, Bing Vemuri, Baba C. Oezarslan, Evren BE Laidlaw, D Weickert, J TI A Mixture of Wisharts (MOW) Model for Multifiber Reconstruction SO VISUALIZATION AND PROCESSING OF TENSOR FIELDS: ADVANCES AND PERSPECTIVES SE Mathematics and Visualization LA English DT Article; Book Chapter ID DIFFUSION-WEIGHTED MRI; FIBER ORIENTATIONS; HUMAN BRAIN; RESOLUTION; TENSOR; TRACKING; SIGNAL; DECONVOLUTION; ARCHITECTURE; COEFFICIENT AB Diffusion-weighted magnetic resonance imaging (DW-MRI) is a noninvasive imaging technique that allows neural tissue architecture, to be probed at a microscopic scale in vivo. By producing quantitative data on the motion of water molecules that naturally occurs in brain tissues as part of the physical diffusion process; DW-MRI can be used to map the fiber paths in the brain white matter. Estimating the local complex architecture in the presence of intra-voxel heterogeneity caused by multiple fiber pathways is of great importance and requires sophisticated modeling techniques. In this chapter, we present a review of our recently introduced novel mathematical model [27] and an accompanying unified computational Framework for spherical deconvolution to perform multi-fiber reconstruction [28]. In our model, the diffusion-weighted MR signal attenuation is characterized by the Laplace transform of a continuous mixture of diffusion tensors. When the mixing distribution is a Wishart distribution; the Laplace transform yields a, closed form expression. Additionally, we show that the traditional diffusion tensor model is a limiting case of this continuous mixture of tensors model. We then formulate the reconstruction problem in a unified deconvolution framework that facilitates investigation of several deconvolution schemes and achieves stable, sparse and accurate solutions. Finally, we present, results of testing this theoretical model and the accompanying unified computational framework, on synthetic data and real rat brain data. The comparisons with several competing methods empirically suggest that the proposed model yields efficient and accurate solutions in the presence of intra-voxel orientational heterogeneity. C1 [Jian, Bing; Vemuri, Baba C.] Univ Florida, Dept Comp & Informat Sci & Engn, Gainesville, FL 32611 USA. [Oezarslan, Evren] NICHD, Sect Tissue Biophys & Biomimet, LIMB, NIH, Bethesda, MD 20892 USA. [Vemuri, Baba C.] E324 Univ Florida, Dept CISE, Ctr Vis Graph & Med Imaging, Gainesville, FL 32611 USA. RP Jian, B (reprint author), Univ Florida, Dept Comp & Informat Sci & Engn, POB 116120,Room E331,CISE Bldg, Gainesville, FL 32611 USA. EM bjian@cise.ufl.edu; vemuri@cise.ufl.edu; evren@helix.nih.gov RI Ozarslan, Evren/B-4858-2013 OI Ozarslan, Evren/0000-0003-0859-1311 NR 45 TC 3 Z9 3 U1 0 U2 1 PU SPRINGER-VERLAG BERLIN PI BERLIN PA HEIDELBERGER PLATZ 3, D-14197 BERLIN, GERMANY SN 1612-3786 BN 978-3-540-88377-7 J9 MATH VIS PY 2009 BP 39 EP 56 DI 10.1007/978-3-540-88378-4_3 D2 10.1007/978-3-540-88378-4 PG 18 WC Computer Science, Artificial Intelligence; Mathematics, Applied; Imaging Science & Photographic Technology SC Computer Science; Mathematics; Imaging Science & Photographic Technology GA BJU86 UT WOS:000267219100003 ER PT S AU Kehrl, JH Hwang, IY Park, C AF Kehrl, John H. Hwang, Il-Young Park, Chung BE McGavern, D Dustin, M TI Chemoattractant Receptor Signaling and Its Role in Lymphocyte Motility and Trafficking SO VISUALIZING IMMUNITY SE Current Topics in Microbiology and Immunology LA English DT Review; Book Chapter ID T-CELL MOTILITY; HETEROTRIMERIC G-PROTEINS; HIGH ENDOTHELIAL VENULES; IN-VIVO; PHOSPHOINOSITIDE 3-KINASE; SPHINGOSINE 1-PHOSPHATE; LEUKOCYTE MIGRATION; RGS PROTEINS; 2-PHOTON MICROSCOPY; IMMUNE FUNCTION AB Intravital microscopy has provided extraordinary glimpses of lymphocytes crossing high endothelial venules, detailed the movements and interactions of lymphocytes within lymph organs, and recorded lymphocytes crossing the lymphatic endothelium into the efferent lymph. Helping to orchestrate these movements are signals generated by the engagement of chemoattractants with their cognate receptors. Chemokines present on high endothelial venules and within lymph organs, and the high levels of sphingosine I-phosphate in the lymph provide signposts to help guide lymphocytes and provide intracellular signals that affect lymphocyte polarity and motility. Within lymph nodes, T and B lymphocytes migrate along networks of fibroblastic reticular cells and follicular dendritic, respectively, which provide an adhesive platform and solid phased chemokines. Illustrating the importance of chemoattractant receptors in these processes, lymphocytes that lack CXCR4, CXCR5, CCR7, or S1PR1, or which lack crucial signaling molecules activated by these receptors, exhibit defects in lymph node entrance, positioning, polarity, motility, and/or lymph node egress. This review will focus on the contributions of in vivo imaging of lymphocytes from various mouse mutants to our understanding of the roles chemoattractants play in lymphocyte entrance into and exit from lymph nodes, and in coordinating and facilitating the movements of lymphocytes within lymph nodes. C1 [Kehrl, John H.; Hwang, Il-Young; Park, Chung] NIAID, Cell Mol Immunol Sect B, Immunoregulat Lab, NIH, Bethesda, MD 20892 USA. RP Kehrl, JH (reprint author), NIAID, Cell Mol Immunol Sect B, Immunoregulat Lab, NIH, 10 Ctr Dr, Bethesda, MD 20892 USA. EM jkehrl@niaid.nih.gov; jkehrl@niaid.nih.gov; jkehrl@niaid.nih.gov OI Kehrl, John/0000-0002-6526-159X FU Intramural NIH HHS NR 82 TC 20 Z9 20 U1 0 U2 1 PU SPRINGER-VERLAG BERLIN PI BERLIN PA HEIDELBERGER PLATZ 3, D-14197 BERLIN, GERMANY SN 0070-217X BN 978-3-540-93862-0 J9 CURR TOP MICROBIOL JI Curr.Top.Microbiol.Immunol. PY 2009 VL 334 BP 107 EP 127 DI 10.1007/978-3-540-93864-4_5 D2 10.1007/978-3-540-93864-4 PG 21 WC Engineering, Biomedical; Immunology; Microbiology SC Engineering; Immunology; Microbiology GA BKM58 UT WOS:000268504000005 PM 19521683 ER PT S AU Kang, SS McGavern, DB AF Kang, Silvia S. McGavern, Dorian B. BE McGavern, D Dustin, M TI Inflammation on the Mind: Visualizing Immunity in the Central Nervous System SO VISUALIZING IMMUNITY SE Current Topics in Microbiology and Immunology LA English DT Review; Book Chapter ID EXPERIMENTAL AUTOIMMUNE ENCEPHALOMYELITIS; LYMPHOCYTIC-CHORIOMENINGITIS-VIRUS; CYTOTOXIC T-LYMPHOCYTES; GREEN FLUORESCENT PROTEIN; BLOOD-BRAIN-BARRIER; POSITRON-EMISSION-TOMOGRAPHY; DEEP CERVICAL LYMPH; CLASS-I MOLECULES; EXPERIMENTAL ALLERGIC ENCEPHALOMYELITIS; MYELIN OLIGODENDROCYTE GLYCOPROTEIN AB The central nervous system (CNS) is a remarkably complex structure that utilizes electrochemical signaling to coordinate activities throughout the entire body. Because the nervous system contains nonreplicative cells, it is postulated that, through evolutionary pressures, this compartment has acquired specialized mechanisms to limit damage. One potential source of damage comes from our immune system, which has the capacity to survey the CNS and periphery for the presence of foreign material. The immune system is equipped with numerous effector mechanisms and can greatly alter the homeostasis and function of the CNS. Degeneration, autoimmunity, and pathogen infection can all result in acute, and sometimes chronic, inflammation within the CNS. Understanding the specialized functionality of innate and adaptive immune cells within the CNS is critical to the design of more efficacious treatments to mitigate CNS inflammatory conditions. Much of our knowledge of CNS-immune interactions stems from seminal studies that have used static and dynamic imaging approaches to visualize inflammatory cells responding to different CNS conditions. This review will focus on how imaging techniques have elevated our understanding of CNS inflammation as well as the exciting prospects that lie ahead as we begin to pursue investigation of the inflamed CNS in real time. C1 [Kang, Silvia S.; McGavern, Dorian B.] NINDS, NIH, Bethesda, MD 20892 USA. RP McGavern, DB (reprint author), NINDS, NIH, 10 Ctr Dr,Bldg 10,Rm 7C213, Bethesda, MD 20892 USA. EM mcgavernd@mail.nih.gov OI McGavern, Dorian/0000-0001-9568-545X FU Intramural NIH HHS [ZIA NS003112-07]; NIAID NIH HHS [AI 070967-01, AI 075298-01, R01 AI070967, R01 AI075298, R56 AI075298]; NINDS NIH HHS [NS 061447-01, F32 NS061447] NR 204 TC 5 Z9 5 U1 0 U2 1 PU SPRINGER-VERLAG BERLIN PI BERLIN PA HEIDELBERGER PLATZ 3, D-14197 BERLIN, GERMANY SN 0070-217X BN 978-3-540-93862-0 J9 CURR TOP MICROBIOL JI Curr.Top.Microbiol.Immunol. PY 2009 VL 334 BP 227 EP 263 DI 10.1007/978-3-540-93864-4_10 D2 10.1007/978-3-540-93864-4 PG 37 WC Engineering, Biomedical; Immunology; Microbiology SC Engineering; Immunology; Microbiology GA BKM58 UT WOS:000268504000010 PM 19521688 ER PT S AU Zhang, L Xiong, W AF Zhang, Li Xiong, Wei BE Litwack, G TI MODULATION OF THE CYS-LOOP LIGAND-GATED ION CHANNELS BY FATTY ACID AND CANNABINOIDS SO VITAMINS AND HORMONES: ANANDAMIDE AN ENDOGENOUS CANNABINOID SE Vitamins and Hormones LA English DT Review; Book Chapter ID NICOTINIC ACETYLCHOLINE-RECEPTORS; RAT SPINAL-CORD; 5-HT3 RECEPTORS; GLYCINE RECEPTORS; ARACHIDONIC-ACID; XENOPUS OOCYTES; SYNAPTIC-TRANSMISSION; MEDIATED RESPONSES; DOCOSAHEXAENOIC ACID; CHLORIDE CHANNEL AB The Cys-loop ligand-gated ion channel (LGIC) family comprises a group of membrane ion channel receptors that play a crucial rote in fast synaptic neurotransmission in the central and peripheral nervous system. The members of this superfamily include gamma-aminobutyric acid type A (GABA(A)), neuronal nicotinic acetylcholine (nACh), 5-HT(3), and glycine receptors. These receptors serve as therapeutic sites for general anesthetic, antipsychoactive, antinociceptive, and anxiolytic drugs in the brain. These receptors are also thought to be primary targets of alcohol and other drugs of abuses. A number of studies reported that fatty acids affected the function of GABA(A) receptors in the early nineties. Accumulating evidence has suggested that the derivatives of arachidonic acid (AA), such as anandamide (N-arachidonoylethanolamine, AEA) and arachidonoylglycerol (2-AG), can critically regulate the other members of the Cys-loop LGIC superfamily through a cannabinoid receptor-independent mechanism. This chapter focuses on the results of recent studies showing that the Cys-loop LGICs could be additional molecular targets for fatty acid and endocannabinoid action in the central and peripheral nervous system. Some of these targets may mediate behavioral effects for cannabinoids to alter neuronal function. C1 [Zhang, Li; Xiong, Wei] NIAAA, Lab Integrat Neurosci, NIH, Rockville, MD 20852 USA. RP Zhang, L (reprint author), NIAAA, Lab Integrat Neurosci, NIH, Rockville, MD 20852 USA. RI Xiong, Wei/F-8251-2011 NR 80 TC 6 Z9 6 U1 0 U2 1 PU ELSEVIER ACADEMIC PRESS INC PI SAN DIEGO PA 525 B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 USA SN 0083-6729 BN 978-0-12-374782-2 J9 VITAM HORM JI Vitam. Horm. PY 2009 VL 81 BP 315 EP 335 DI 10.1016/S0083-6729(09)81012-1 PG 21 WC Biochemistry & Molecular Biology; Endocrinology & Metabolism SC Biochemistry & Molecular Biology; Endocrinology & Metabolism GA BKU39 UT WOS:000269266800012 PM 19647117 ER PT S AU Toth, A Blumberg, PM Boczan, J AF Toth, Attila Blumberg, Peter M. Boczan, Judit BE Litwack, G TI ANANDAMIDE AND THE VANILLOID RECEPTOR (TRPV1) SO VITAMINS AND HORMONES: ANANDAMIDE AN ENDOGENOUS CANNABINOID SE Vitamins and Hormones LA English DT Review; Book Chapter ID PRIMARY SENSORY NEURONS; ROOT GANGLION NEURONS; PROTEIN-KINASE-C; ENDOGENOUS CANNABINOID ANANDAMIDE; ACID AMIDE HYDROLASE; ENDOCANNABINOID TRANSPORTER INHIBITORS; CENTRAL-NERVOUS-SYSTEM; DORSAL-HORN NEURONS; CAPSAICIN RECEPTOR; IN-VITRO AB Arachidonylethanolamide (anandamide) was identified some 15 years ago as a brain constituent that binds to the cannabinoid receptor. After this seminal discovery, multiple new receptors for anandamide have been identified, including the vanilloid receptor (TRPV1), and anandamide is now frequently referred as an "endovanilloid." Characterization of the action of anandamide on TRPV1 revealed that (1) the potency and efficacy of anandamide on TRPV1 very much depend on the species and tissue, (2) anandamide responsiveness in vivo is significantly controlled by its local metabolism, (3) anandamide activation of cannabinoid receptors regulates TRPV1 responsiveness, (4) TRPV1 activation regulates anandamide synthesis, (5) anandamide metabolites affect TRPV1 responses, (6) the often observed convergent physiological actions of anandamide and TRPV1 agonists in neither case necessarily represent direct effects on TRPV1, and (7) coactivation of the cannabinoid receptors and TRPV1 often complicates the distinction between these pathways. These issues are reviewed here together with the potential implications for the pathophysiological and pharmacological regulation of inflammatory, respiratory, and cardiovascular disorders, as well as of appetite and fat metabolism. C1 [Toth, Attila] Univ Debrecen, Inst Cardiol, Div Clin Physiol, H-4012 Debrecen, Hungary. [Blumberg, Peter M.] NCI, Mol Mech Tumor Promot Sect, Lab Canc Biol & Genet, NIH, Bethesda, MD 20892 USA. [Boczan, Judit] Univ Debrecen, Dept Neurol, H-4012 Debrecen, Hungary. RP Toth, A (reprint author), Univ Debrecen, Inst Cardiol, Div Clin Physiol, H-4012 Debrecen, Hungary. RI Toth, Attila/F-4859-2010 OI Toth, Attila/0000-0001-6503-3653 NR 142 TC 40 Z9 40 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 0083-6729 BN 978-0-12-374782-2 J9 VITAM HORM JI Vitam. Horm. PY 2009 VL 81 BP 389 EP 419 DI 10.1016/S0083-6729(09)81015-7 PG 31 WC Biochemistry & Molecular Biology; Endocrinology & Metabolism SC Biochemistry & Molecular Biology; Endocrinology & Metabolism GA BKU39 UT WOS:000269266800015 PM 19647120 ER PT J AU Siantar, CH Taylor, TP Coleman, CN AF Siantar, Christine Hartmann Taylor, Tammy P. Coleman, C. Norman BE Maurer, SM TI Recovering from Nuclear and Radiological Attacks SO WMD TERRORISM: SCIENCE AND POLICY CHOICES LA English DT Article; Book Chapter C1 [Siantar, Christine Hartmann] Lawrence Livermore Natl Lab, Livermore, CA 94550 USA. [Coleman, C. Norman] Natl Canc Inst, Radiat Oncol Sci Program, Bethesda, MD 20892 USA. RP Siantar, CH (reprint author), Lawrence Livermore Natl Lab, Livermore, CA 94550 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU M I T PRESS PI CAMBRIDGE PA FIVE CAMBRIDGE CENTER, CAMBRIDGE, MA 02142 USA BN 978-0-262-01298-0 PY 2009 BP 329 EP 364 PG 36 WC Planning & Development; Public Administration SC Public Administration GA BPL40 UT WOS:000279133000013 ER PT J AU Vines, AI Ta, M Esserman, D Baird, DD AF Vines, Anissa I. Ta, Myduc Esserman, Denise Baird, Donna D. TI A Comparison of the Occurrence and Perceived Stress of Major Life Events in Black and White Women SO WOMEN & HEALTH LA English DT Article DE stress; life events; race; women's health ID AFRICAN-AMERICAN; SOCIOECONOMIC-STATUS; DEPRESSIVE SYMPTOMS; SOCIAL SUPPORT; HEALTH; DISCRIMINATION; GENDER; RACE; EPIDEMIOLOGY; INEQUALITIES AB Purpose: To describe the occurrence and perceived stress of major life events, and to investigate whether adjusting for socioeconomic status reduced race/ethnicity differences. Methods: Black (n = 639) and white (n = 419) women aged 35-49 years responded to 14 major life event questions within the domains of employment, health, relationship, finance, residential change, and crime. Main Findings: The total number of life events did not differ by race/ethnicity, but black women reported significantly more events in the domains of relationship, financial, and residential change than white women. White women generally reported higher stress for a given event than black women, although for "residential change'' black women reported more severe stress than the white women. Conclusions: Inclusion of both the occurrence and perceived stress of major life events can improve our understanding of how this stressor may affect health. C1 [Vines, Anissa I.; Ta, Myduc] Univ N Carolina, Gillings Sch Global Publ Hlth, Dept Epidemiol, Chapel Hill, NC 27599 USA. [Esserman, Denise] Univ N Carolina, Sch Med, Dept Med, Chapel Hill, NC 27599 USA. [Baird, Donna D.] NIEHS, Res Triangle Pk, NC 27709 USA. RP Vines, AI (reprint author), Univ N Carolina, Gillings Sch Global Publ Hlth, Dept Epidemiol, 266 Rosenau Hall,CB 7435, Chapel Hill, NC 27599 USA. EM avines@email.unc.edu RI Baird, Donna/D-5214-2017 OI Baird, Donna/0000-0002-5544-2653 FU NICHD NIH HHS [R03 HD055029-02, R03 HD055029] NR 29 TC 5 Z9 5 U1 1 U2 3 PU HAWORTH PRESS INC PI BINGHAMTON PA 10 ALICE ST, BINGHAMTON, NY 13904-1580 USA SN 0363-0242 J9 WOMEN HEALTH JI Women Health PY 2009 VL 49 IS 5 BP 368 EP 380 DI 10.1080/03630240903238743 PG 13 WC Public, Environmental & Occupational Health; Women's Studies SC Public, Environmental & Occupational Health; Women's Studies GA 517LR UT WOS:000271616300002 PM 19851943 ER PT J AU Bustamante, ML Villarroel, J Francesetti, V Rios, M Arcos-Burgos, M Jerez, S Iturra, P Solari, A Silva, H AF Bustamante, M. Leonor Villarroel, Juana Francesetti, Valeria Rios, Matias Arcos-Burgos, Mauricio Jerez, Sonia Iturra, Patricia Solari, Aldo Silva, Hernan TI Planning in borderline personality disorder: Evidence for distinct subpopulations SO WORLD JOURNAL OF BIOLOGICAL PSYCHIATRY LA English DT Article DE Borderline personality disorder; neuropsychological tests; impulsivity ID EXECUTIVE FUNCTION DEFICITS; COGNITIVE FUNCTION; MEMORY; PSYCHOPATHOLOGY; NEUROPSYCHOLOGY; IMPULSIVITY; SCALE; ADHD AB Objective. Borderline personality disorder is a severe mental disorder, whereas previous studies suggest executive functions may be impaired. The aim of this study was to evaluate executive planning in a sample of 85 individuals. Methods. Planning was assessed by means of the Tower of London (Drexel University version) task. Latent class cluster analysis models were adjusted to the data. Results. We identified two different subpopulations of borderline personality disorder patients, one of them with significantly reduced performance. Conclusion. Neuropsychological mechanisms may be involved in borderline personality disorder, at least in a subgroup of patients. C1 [Bustamante, M. Leonor; Villarroel, Juana; Jerez, Sonia; Silva, Hernan] Univ Chile, Clin Hosp, Dept Psychiat & Mental Hlth, Personal Disorders Unit, Santiago, Chile. [Bustamante, M. Leonor; Iturra, Patricia; Solari, Aldo] Univ Chile, Fac Med, Inst Biomed Sci, Santiago 7, Chile. [Francesetti, Valeria; Rios, Matias] Univ Chile, Fac Social Sci, Santiago 7, Chile. [Arcos-Burgos, Mauricio] Univ Miami, Leonard M Miller Sch Med, Dept Psychiat & Behav Sci, Coral Gables, FL 33124 USA. [Arcos-Burgos, Mauricio] NIH, Med Genet Branch, Bethesda, MD 20892 USA. RP Bustamante, ML (reprint author), Univ Chile, Clin Hosp, Dept Psychiat, Personal Disorders Unit, Av La Paz 1003, Santiago, Chile. EM mbustamante@med.uchile.cl RI Bustamante, Maria Leonor/H-3728-2014 OI Bustamante, Maria Leonor/0000-0001-9071-2463 FU Fondo Nacional de Desarrollo Cientifico y Tecnologico (FONDECYT) [1071045]; Clinical Hospital of the University of Chile [193/06] FX This work was financed by the Fondo Nacional de Desarrollo Cientifico y Tecnologico (FONDECYT) Project 1071045 and by the Oficina de Apoyo a la Investigacion Cientifica (OAIC) from the Clinical Hospital of the University of Chile, Project 193/06. NR 34 TC 3 Z9 3 U1 1 U2 2 PU INFORMA HEALTHCARE PI LONDON PA TELEPHONE HOUSE, 69-77 PAUL STREET, LONDON EC2A 4LQ, ENGLAND SN 1562-2975 J9 WORLD J BIOL PSYCHIA JI World J. Biol. Psychiatry PY 2009 VL 10 IS 4 BP 512 EP 517 DI 10.3109/15622970903079481 PN 2 PG 6 WC Psychiatry SC Psychiatry GA 535WS UT WOS:000273003200022 PM 19658046 ER PT J AU Liu, A Chen, Y Yang, Z Feng, Y Rui, W Luo, W Liu, Y Gonzalez, FJ Dai, R AF Liu, A. Chen, Y. Yang, Z. Feng, Y. Rui, W. Luo, W. Liu, Y. Gonzalez, F. J. Dai, R. TI New metabolites of fenofibrate in Sprague-Dawley rats by UPLC-ESI-QTOF-MS-based metabolomics coupled with LC-MS/MS SO XENOBIOTICA LA English DT Article DE Metabolomics; metabolites; metabolism pathway; fenofibrate; rat ID ACTIVATED RECEPTOR-ALPHA; PPAR-ALPHA; PEROXISOME PROLIFERATORS; SPECIES-DIFFERENCES; HEPATIC PEROXISOME; CLOFIBRIC ACID; HEPATOCARCINOGENESIS; DISPOSITION; METABONOMICS; MECHANISM AB Fenofibrate has been widely used for the treatment of dyslipidaemia with a long history. Species differences of its metabolism were reported, but its metabolites in rodent have not been fully investigated. Urine and plasma samples were collected before and after oral dosages of fenofibrate in Sprague-Dawley rats. Urine samples were subjected to ultra-performance liquid chromatography-electrospray ionization quadrupole time-of-flight mass spectrometry (UPLC-ESI-QTOF-MS) analysis, and projection to latent structures discriminant analysis was used for the identification of metabolites. New metabolites in urine and plasma were also studied by liquid chromatography-tandem mass spectrometry (LC-MS/MS). The metabolism pathway was studied in rat hepatocytes. Synthesized and purchased authentic compounds were used for metabolite identification by LC-MS/MS. Five ever-reported metabolites were identified and another four new ones were found. Among these new metabolites, fenofibric acid taurine and reduced fenofibric acid taurine indicate new phase II conjugation pathway of fenofibrate. C1 [Liu, A.; Chen, Y.; Yang, Z.; Luo, W.; Liu, Y.; Dai, R.] Chinese Acad Sci, Guangzhou Inst Biomed & Hlth, Guangzhou 510663, Guangdong, Peoples R China. [Feng, Y.; Rui, W.] Guangdong Pharmaceut Univ, Guangzhou, Guangdong, Peoples R China. [Gonzalez, F. J.] NCI, NIH, Bethesda, MD 20892 USA. RP Dai, R (reprint author), Chinese Acad Sci, Guangzhou Inst Biomed & Hlth, Guangzhou 510663, Guangdong, Peoples R China. EM dai_renke@gibh.ac.cn FU Intramural NIH HHS [Z01 BC005562-21] NR 28 TC 16 Z9 18 U1 3 U2 16 PU TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXON, ENGLAND SN 0049-8254 J9 XENOBIOTICA JI Xenobiotica PY 2009 VL 39 IS 4 BP 345 EP 354 AR PII 909819518 DI 10.1080/00498250802680827 PG 10 WC Pharmacology & Pharmacy; Toxicology SC Pharmacology & Pharmacy; Toxicology GA 434VU UT WOS:000265303000007 PM 19350456 ER PT S AU Bandettini, PA AF Bandettini, Peter A. BE Miller, MB Kingstone, A TI What's New in Neuroimaging Methods? SO YEAR IN COGNITIVE NEUROSCIENCE 2009 SE Annals of the New York Academy of Sciences LA English DT Article DE functional MRI (fMRI); voxel-based morphometry (VBM); diffusion tensor imaging (DTI); diffusion spectrum imaging (DSI); magnetoencephalography (MEG); electroencephalography (EEG); optical imaging; diffuse optical tomography (DOT); endogenous oscillations; default network; resting state fluctuations; fMRI decoding; multivariate analysis; positron emission tomography (PET); region of interest (ROI) ID VOXEL-BASED MORPHOMETRY; GRAY-MATTER DENSITY; STATE FUNCTIONAL CONNECTIVITY; APPARENT-DIFFUSION-COEFFICIENT; DEFAULT-MODE NETWORK; CEREBRAL-BLOOD-FLOW; HUMAN VISUAL-CORTEX; ATTENTION-DEFICIT/HYPERACTIVITY DISORDER; ENDOGENOUS BRAIN OSCILLATIONS; TASK-INDUCED DEACTIVATION AB The rapid advancement of neuroimaging methodology and its growing availability has transformed neuroscience research. The answers to many questions that we ask about how the brain is organized depend on the quality of data that we are able to obtain about the locations, dynamics, fluctuations, magnitudes, and types of brain activity and structural changes. In this review an attempt is made to take a snapshot of the cutting edge of a small. component of the very rapidly evolving field of neuroimaging. For each area covered, a brief context is provided along with a summary of a few of the current developments and issues. Then, several outstanding papers, published in the past year or so, are described, providing an example of the directions in which each area is progressing. The areas covered include functional magnetic resonance imaging (fMRI), voxel-based morphometry (VBM), diffusion tensor imaging (DTI), electroencephalography (EEG), magnetoencephalography (MEG), optical imaging, and positron emission tomography (PET). More detail is included on fMRI; its subsections include fMRI interpretation, new fMRI contrasts, MRI technology, MRI paradigms and processing, and endogenous oscillations in fMRI. C1 NIMH, Sect Funct Imaging Methods, Bethesda, MD 20894 USA. RP Bandettini, PA (reprint author), NIMH, Sect Funct Imaging Methods, Bldg 10,Rm LD80,10 Ctr Dr, Bethesda, MD 20894 USA. EM bandettini@nih.gov FU Intramural NIH HHS [Z01 MH002783-06] NR 211 TC 98 Z9 99 U1 4 U2 46 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN STREET, MALDEN 02148, MA USA SN 0077-8923 BN 978-1-57331-752-8 J9 ANN NY ACAD SCI JI Ann.NY Acad.Sci. PY 2009 VL 1156 BP 260 EP 293 DI 10.1111/j.1749-6632.2009.04420.x PG 34 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA BJH40 UT WOS:000265827700013 PM 19338512 ER PT J AU Kim, EJ Ro, H Huh, TL Lee, CJ Choi, J Rhee, M AF Kim, Eun-joong Ro, Hyunju Huh, Tae-Lin Lee, Chang Joong Choi, Jinhee Rhee, Myungchull TI A Novel Kinesin-like Protein, Surhe is Associated with Dorsalization in the Zebrafish Embryos SO ANIMAL CELLS AND SYSTEMS LA English DT Article DE kinesin-like protein; Surhe; dorsal determinant; dorsalization ID BETA-CATENIN; SUPERFAMILY PROTEIN; MEDIATED TRANSPORT; DORSOVENTRAL AXIS; MOLECULAR MOTORS; XENOPUS EMBRYOS; LIGHT-CHAIN; YOLK CELL; MESODERM; DOMAIN AB We are reporting the expression patterns and possible biological functions of a novel Kinesin-like protein, Surhe, in the zebrafish. Homology studies of derived amino acid sequences suggest that Surhe has an amino-terminal kinesin motor domain that is similar to that of the emerging MKLP-1 subfamily [Kim and Endow, 2000] and two coiled-coil domains in a central region. Cellular localization studies in mammalian cells revealed that Surhe protein is located in cytoplasm, suggesting that Surhe may be involved in the intracellular transport. During the developmental process, surhe transcripts are highly expressed in early embryonic stages. Overexpression of the dominant negative form of Surhe significantly down-regulates the dorsalization markers, such as goosecoid, bozozok, and chordin. Taken together, we postulate that Surhe may be involved in dorsalization process as a motor molecule. C1 [Rhee, Myungchull] Chungnam Natl Univ, Coll Biosyst Sci, Dept Biol, Taejon 305764, South Korea. [Kim, Eun-joong] Seoul Natl Univ, Sch Pharm, Seoul 151741, South Korea. [Ro, Hyunju] NICHD, NIH, LMG, Bethesda, MD 20892 USA. [Huh, Tae-Lin] Kyungpook Natl Univ, Dept Genet Engn, Taegu 702701, South Korea. [Lee, Chang Joong] Inha Univ, Coll Nat Sci, Dept Biol, Inchon 402751, South Korea. [Choi, Jinhee] Univ Seoul, Coll Urban Sci, Fac Environm Engn, Seoul 130743, South Korea. RP Rhee, M (reprint author), Chungnam Natl Univ, Coll Biosyst Sci, Dept Biol, Taejon 305764, South Korea. EM mrhee@cnu.ac.kr FU Korean Government [KRF-2005-070-C00118]; Korean Ministry of Environment [091-081-077] FX Grant sponsors for this work: the Korean Research Foundation Grant funded by the Korean Government (MOE HRD); Grant number: KRF-2005-070-C00118; the Korean Ministry of Environment as "The Eco-technopia 21 Project" (Grant number: 091-081-077) NR 44 TC 4 Z9 4 U1 0 U2 3 PU ZOOLOGICAL SOC KOREA PI SEOUL PA KOREA SCIENCE & TECHNOLOGY CENTER, ROOM 1002, 635-4 YEOKSAM-DONG, KANGNAM-GU, SEOUL, 135-703, SOUTH KOREA SN 1976-8354 J9 ANIM CELLS SYST JI Anim. Cells Syst. PD DEC 31 PY 2008 VL 12 IS 4 BP 219 EP 230 DI 10.1080/19768354.2008.9647176 PG 12 WC Cell Biology; Zoology SC Cell Biology; Zoology GA 398NY UT WOS:000262740000005 ER PT J AU Ding, JX Jiang, D Kurczy, M Nalepka, J Dudley, B Merkel, EI Porter, FD Ewing, AG Winograd, N Burgess, J Molyneaux, K AF Ding, Jiaxi Jiang, DeChen Kurczy, Michael Nalepka, Jennifer Dudley, Brian Merkel, Erin I. Porter, Forbes D. Ewing, Andrew G. Winograd, Nicholas Burgess, James Molyneaux, Kathleen TI Inhibition of HMG CoA reductase reveals an unexpected role for cholesterol during PGC migration in the mouse SO BMC DEVELOPMENTAL BIOLOGY LA English DT Article ID PRIMORDIAL GERM-CELLS; PLASMA-MEMBRANE CHOLESTEROL; LIPID RAFTS; EMBRYONIC LETHALITY; MICE LACKING; HEDGEHOG; BIOSYNTHESIS; ISOPRENOIDS; GONADS; PROLIFERATION AB Background: Primordial germ cells (PGCs) are the embryonic precursors of the sperm and eggs. Environmental or genetic defects that alter PGC development can impair fertility or cause formation of germ cell tumors. Results: We demonstrate a novel role for cholesterol during germ cell migration in mice. Cholesterol was measured in living tissue dissected from mouse embryos and was found to accumulate within the developing gonads as germ cells migrate to colonize these structures. Cholesterol synthesis was blocked in culture by inhibiting the activity of HMG CoA reductase (HMGCR) resulting in germ cell survival and migration defects. These defects were rescued by co-addition of isoprenoids and cholesterol, but neither compound alone was sufficient. In contrast, loss of the last or penultimate enzyme in cholesterol biosynthesis did not alter PGC numbers or position in vivo. However embryos that lack these enzymes do not exhibit cholesterol defects at the stage at which PGCs are migrating. This demonstrates that during gestation, the cholesterol required for PGC migration can be supplied maternally. Conclusion: In the mouse, cholesterol is required for PGC survival and motility. It may act cell-autonomously by regulating clustering of growth factor receptors within PGCs or non cell-autonomously by controlling release of growth factors required for PGC guidance and survival. C1 [Ding, Jiaxi; Nalepka, Jennifer; Dudley, Brian; Molyneaux, Kathleen] Case Western Reserve Univ, Dept Genet, Cleveland, OH 44106 USA. [Jiang, DeChen; Burgess, James] Case Western Reserve Univ, Dept Chem, Cleveland, OH 44106 USA. [Kurczy, Michael; Ewing, Andrew G.; Winograd, Nicholas] Penn State Univ, Dept Chem, University Pk, PA 16802 USA. [Merkel, Erin I.; Porter, Forbes D.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Program Dev Endocrinol & Genet, NIH, Bethesda, MD USA. [Ewing, Andrew G.] Gothenburg Univ, Dept Chem, SE-41296 Gothenburg, Sweden. RP Molyneaux, K (reprint author), Case Western Reserve Univ, Dept Genet, Cleveland, OH 44106 USA. EM jiaxi.ding@osumc.edu; dechen.jiang@case.edu; mek20@psu.edu; jennifer.nalepka@case.edu; brian.dudley@case.edu; merkele@mail.nih.edu; fdporter@mail.nih.gov; age@psu.edu; nxw@psu.edu; jdb22@case.edu; kam53@case.edu RI Ewing, Andrew/A-3650-2009; OI Kurczy, Michael/0000-0001-6579-9691; Winograd, Nicholas/0000-0002-2690-7714 FU NIH-NCRR [RR-017980-01]; Case Western; Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) FX We acknowledge Patty Conrad for microscopy assistance. Funding support for the Leica AOBS confocal multi-user facility was supplied by a grant from NIH-NCRR (RR-017980-01). We thank Joe Nadeau, Jenny Liang and Helen Salz for critical reading of the manuscript. The MC-480/SSEA1 antibody developed by David Solter was obtained for the Developmental Studies Hybridoma Bank developed under the auspices of the NICHD and maintained by the University of Iowa, Department of Biological Sciences, Iowa City, IA 52242. Financial support for this project was supplied by Case Western. This work was also funded in part by the intramural research of the Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD). NR 44 TC 12 Z9 13 U1 0 U2 5 PU BIOMED CENTRAL LTD PI LONDON PA CURRENT SCIENCE GROUP, MIDDLESEX HOUSE, 34-42 CLEVELAND ST, LONDON W1T 4LB, ENGLAND SN 1471-213X J9 BMC DEV BIOL JI BMC Dev. Biol. PD DEC 31 PY 2008 VL 8 AR 120 DI 10.1186/1471-213X-8-120 PG 14 WC Developmental Biology SC Developmental Biology GA 402ZT UT WOS:000263052300001 PM 19117526 ER PT J AU Esibizione, D Cui, CY Schlessinger, D AF Esibizione, Diana Cui, Chang-Yi Schlessinger, David TI Candidate EDA targets revealed by expression profiling of primary keratinocytes from Tabby mutant mice SO GENE LA English DT Article DE Anhidrotic ectodermal dysplasia; Ectodysplasin; Edar; Tbx1; Bmp7; Jag1 ID ANHIDROTIC ECTODERMAL DYSPLASIA; HAIR FOLLICLE DEVELOPMENT; SKIN; GROWTH; CELL; IMMUNODEFICIENCY; DIFFERENTIATION; INVOLVEMENT; INDUCTION; PSORIASIS AB EDA, the gene mutated in anhidrotic ectodermal dysplasia, encodes ectodysplasin, a TNF superfamily member that activates NF-kappa B mediated transcription. To identify EDA target genes, we have earlier used expression profiling to infer genes differentially expressed at various developmental time points in Tabby (Eda-deficient) compared to wild-type mouse skin. To increase the resolution to find genes whose expression may be restricted to epidermal cells, we have now extended studies to primary keratinocyte cultures established from E19 wild-type and Tabby skin. Using microarrays bearing 44,000 gene probes, we found 385 preliminary candidate genes whose expression was significantly affected by Eda loss. By comparing expression profiles to those from Eda-A1 transgenic skin, we restricted the list to 38 "candidate EDA targets", 14 of which were already known to be expressed in hair follicles or epidermis. We confirmed expression changes for 3 selected genes. Tbx1, Bmp7, and Jag1, both in keratinocytes and in whole skin, by Q-PCR and Western blotting analyses. Thus, by the analysis of keratinocytes, novel candidate pathways downstream of EDA were detected. 2008 Published by Elsevier B.V. C1 [Esibizione, Diana; Cui, Chang-Yi; Schlessinger, David] NIA, Genet Lab, NIH, Biomed Res Ctr, Baltimore, MD 21224 USA. [Esibizione, Diana] Univ Bologna, Dept Histol Embryol & Appl Biol, I-40126 Bologna, Italy. RP Schlessinger, D (reprint author), NIA, Genet Lab, NIH, Biomed Res Ctr, 251 Bayview Blvd,Suite 100, Baltimore, MD 21224 USA. EM SchlessingerD@grc.nia.nih.gov FU IRP of the NIH, National Institute on Aging FX We thank Drs. Kunisada M, Ko M, Piao Y and Nagaraja R for their helpful discussions and technical assistances. This work was supported by the IRP of the NIH, National Institute on Aging. NR 35 TC 4 Z9 4 U1 0 U2 4 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0378-1119 J9 GENE JI Gene PD DEC 31 PY 2008 VL 427 IS 1-2 BP 42 EP 46 DI 10.1016/j.gene.2008.09.014 PG 5 WC Genetics & Heredity SC Genetics & Heredity GA 378VX UT WOS:000261353800005 PM 18848976 ER PT J AU Kwong, KY Baskar, S Zhang, H Mackall, CL Rader, C AF Kwong, Ka Yin Baskar, Sivasubramanian Zhang, Hua Mackall, Crystal L. Rader, Christoph TI Generation, Affinity Maturation, and Characterization of a Human Anti-Human NKG2D Monoclonal Antibody with Dual Antagonistic and Agonistic Activity SO JOURNAL OF MOLECULAR BIOLOGY LA English DT Article DE NKG2D; NK cells; human monoclonal antibodies; phage display; antibody engineering ID ACTIVATING IMMUNORECEPTOR NKG2D; IN-VITRO; T-CELLS; CROSS-REACTIVITY; PHAGE DISPLAY; IMMUNE-SYSTEM; NK CELLS; RECEPTOR; LIBRARIES; VIRUS AB In humans, NKG2D is an activating receptor on natural killer (NK) cells and a costimulatory receptor on certain T cells and plays a central role in mediating immune responses in autoimmune diseases, infectious diseases, and cancer. Monoclonal antibodies that antagonize or agonize immune responses mediated by human NKG2D are considered to be of broad and potent therapeutic utility. Nonetheless, monoclonal antibodies to NKG2D that are suitable for clinical investigations have not been published yet. Here, we describe the generation, affinity maturation, and characterization of a fully human monoclonal antibody to human NKG2D. Using phage display technology based on a newly generated naive human Fab library in phage display vector pC3C followed by a tandem chain shuffling process designed for minimal deviation from natural human antibody sequences, we selected a human Fab, designated KYK-2.0, with high specificity and affinity to human NKG2D. KYK-2.0 Fab blocked the binding of the natural human NKG2D ligands MICA, MICB, and ULBP2 as potently as a commercially available mouse anti-human NKG2D monoclonal antibody in immunoglobulin G (IgG) format. Conversion of KYK-2.0 Fab to IgG1 resulted in subnanomolar avidity for human NKG2D. KYK-2.0 IgG1. Was found to selectively recognize defined subpopulations of human lymphocytes known to express NKG2D, that is, the majority of human CD8+, CD16+, and CD56+ cells as well as a small fraction of human CD4+ cells. In solution, KYK-2.0 IgG1 interfered with the cytolytic activity of ex vivo expanded human NK cells. By contrast, immobilized KYK-2.0 IgG1 was found to strongly induce human NK cell activation. The dual antagonistic and agonistic activity promises a wide range of therapeutic applications for KYK-2.0 IgG1 and its derivatives. Published by Elsevier Ltd. C1 [Kwong, Ka Yin; Baskar, Sivasubramanian; Rader, Christoph] NCI, Expt Transplantat & Immunol Branch, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. [Zhang, Hua; Mackall, Crystal L.] NCI, Pediat Oncol Branch, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. RP Rader, C (reprint author), NCI, Expt Transplantat & Immunol Branch, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. EM raderc@mail.nih.gov FU Center for Cancer Research; National Cancer Iristitute; NIH FX This research was supported by the Intramural Research Program of the Center for Cancer Research, National Cancer Iristitute, NIH. We thank Dr. Charles L. Sentman (Dartmouth Medical School, Lebanon, NH) for full-length human NKG2D cDNA; Dr. David H. Margulies (National Institute of Allergy and Infectious Diseases, NIH, Bethesda, MD) for providing access to his BIAcore 2000 instrument; Johan Lindberg and Dr. Alexander Kovacs (Attana AB, Stockholm, Sweden) for facilitating and carrying out quartz crystal microbalance measurements, respectively; Veena Kapoor (National Cancer Institute, NTH, Bethesda, MD) for sorting stable transfectants by fluorescence-activated cell sorting; and Drs. Steven J. Burgess and Francisco Borrego (National Institute of Allergy and Infectious Diseases, NIH, Rockville, MD) for technical advice on the degranulation assay. NR 44 TC 15 Z9 19 U1 0 U2 6 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 31 PY 2008 VL 384 IS 5 BP 1143 EP 1156 DI 10.1016/j.jmb.2008.09.008 PG 14 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 388JR UT WOS:000262016600012 PM 18809410 ER PT J AU Peabody, NC Diao, FQ Luan, HJ Wang, H Dewey, EM Honegger, HW White, BH AF Peabody, Nathan C. Diao, Fengqiu Luan, Haojiang Wang, Howard Dewey, Elizabeth M. Honegger, Hans-Willi White, Benjamin H. TI Bursicon Functions within the Drosophila CNS to Modulate Wing Expansion Behavior, Hormone Secretion, and Cell Death SO JOURNAL OF NEUROSCIENCE LA English DT Article DE ecdysis; eclosion; network; circuit; apoptosis; Drosophila ID INSECT ECDYSIS; IMAGINAL ECDYSIS; MANDUCA-SEXTA; CONTAINING NEURONS; TOBACCO HORNWORM; CASCADE CONTROLS; CUTICLE; MELANOGASTER; ECLOSION; RECEPTOR AB Hormones are often responsible for synchronizing somatic physiological changes with changes in behavior. Ecdysis (i.e., the shedding of the exoskeleton) in insects has served as a useful model for elucidating the molecular and cellular mechanisms of this synchronization, and has provided numerous insights into the hormonal coordination of body and behavior. An example in which the mechanisms have remained enigmatic is the neurohormone bursicon, which, after the final molt, coordinates the plasticization and tanning of the initially folded wings with behaviors that drive wing expansion. The somatic effects of the hormone are governed by bursicon that is released into the blood from neurons in the abdominal ganglion ( the B(AG)), which die after wing expansion. How bursicon induces the behavioral programs required for wing expansion, however, has remained unknown. Here we show by targeted suppression of excitability that a pair of bursicon-immunoreactive neurons distinct from the B(AG) and located within the subesophageal ganglion in Drosophila ( the B(SEG)) is involved in controlling wing expansion behaviors. Unlike the B(AG), the B(SEG) arborize widely in the nervous system, including within the abdominal neuromeres, suggesting that, in addition to governing behavior, they also may modulate the B(AG). Indeed, we show that animals lacking bursicon receptor function have deficits both in the humoral release of bursicon and in posteclosion apoptosis of the B(AG). Our results reveal novel neuromodulatory functions for bursicon and support the hypothesis that the B(SEG) are essential for orchestrating both the behavioral and somatic processes underlying wing expansion. C1 [Peabody, Nathan C.; Diao, Fengqiu; Luan, Haojiang; Wang, Howard; White, Benjamin H.] NIMH, NIH, Mol Biol Lab, Bethesda, MD 20892 USA. [Dewey, Elizabeth M.; Honegger, Hans-Willi] Vanderbilt Univ, Dept Biol Sci, Nashville, TN 37325 USA. RP White, BH (reprint author), NIMH, NIH, Mol Biol Lab, 9000 Rockville Pike, Bethesda, MD 20892 USA. EM benjaminwhite@mail.nih.gov FU National Institute of Mental Health FX This work was supported by the Intramural Research Program of the National Institute of Mental Health. We thank Aaron Hsueh, John Ewer, and John Carlson for reagents, the Bloomington Stock Center for fly lines, and Howard Nash, Grace Gray, and anonymous reviewers for constructive comments on this manuscript. NR 33 TC 43 Z9 45 U1 3 U2 12 PU SOC NEUROSCIENCE PI WASHINGTON PA 11 DUPONT CIRCLE, NW, STE 500, WASHINGTON, DC 20036 USA SN 0270-6474 J9 J NEUROSCI JI J. Neurosci. PD DEC 31 PY 2008 VL 28 IS 53 BP 14379 EP 14391 DI 10.1523/JNEUROSCI.2842-08.2008 PG 13 WC Neurosciences SC Neurosciences & Neurology GA 390AX UT WOS:000262137800007 PM 19118171 ER PT J AU Pavel, J Tang, H Brimijoin, S Moughamian, A Nishioku, T Benicky, J Saavedra, JM AF Pavel, Jaroslau Tang, Hui Brimijoin, Stephen Moughamian, Armen Nishioku, Tsuyoshi Benicky, Julius Saavedra, Juan M. TI Expression and transport of Angiotensin II AT(1) receptors in spinal cord, dorsal root ganglia and sciatic nerve of the rat SO BRAIN RESEARCH LA English DT Article DE Renin angiotensin system; Dorsal root ganglia; Spinal cord; Angiotensin II AT(1) and AT(2) receptor types; Sciatic nerve ligation; Dorsal rhizotomy ID SPONTANEOUSLY HYPERTENSIVE-RATS; SUBTYPE GENE-EXPRESSION; QUANTITATIVE AUTORADIOGRAPHY; SENSORY NEURONS; PERIPHERAL AXOTOMY; PASTE STANDARDS; MESSENGER-RNAS; UP-REGULATION; BRAIN PASTE; SYSTEM AB To clarify the role of Angiotensin II in the regulation of peripheral sensory and motor systems, we initiated a study of the expression, localization and transport of Angiotensin II receptor types in the rat sciatic nerve pathway, including L-4-L-5 spinal cord segments, the corresponding dorsal root ganglia (DRGs) and the sciatic nerve. We used quantitative autoradiography for AT(1) and AT(2) receptors, and in situ hybridization to detect AT(1A), AT(1B) and AT(2) mRNAs. We found substantial expression and discrete localization of Angiotensin II AT(1) receptors, with much higher numbers in the grey than in the white matter. A very high AT(1) receptor expression was detected in the superficial dorsal horns and in neuronal clusters of the DRGs. Expression of AT(1A) mRNA was significantly higher than that of AT(1B). AT(1) receptor binding and AT(1A) and AT(1B) mRNAs were especially prominent in ventral horn motor neurons, and in the DRG neuronal cells. Unilateral dorsal rhizotomy significantly reduced AT(1) receptor binding in the ipsilateral side of the superficial dorsal horn, indicating that a substantial number of dorsal horn AT(1) receptors have their origin in the DRGs. After ligation of the sciatic nerve, there was a high accumulation of AT, receptors proximal to the ligature, a demonstration of anterograde receptor transport. We found inconsistent levels of AT(2) receptor binding and mRNA. Our results suggest multiple roles of Angiotensin II AT(1) receptors in the regulation of sensory and motor functions. Published by Elsevier B.V. C1 [Pavel, Jaroslau; Moughamian, Armen; Nishioku, Tsuyoshi; Benicky, Julius; Saavedra, Juan M.] NIMH, Pharmacol Sect, Bethesda, MD 20892 USA. [Tang, Hui; Brimijoin, Stephen] Mayo Fdn, Dept Mol Pharmacol & Expt Therapeut, Rochester, MN 55905 USA. RP Pavel, J (reprint author), 10 Ctr Dr,MSC 1514,Bldg 10,Rm 2D57, Bethesda, MD 20892 USA. EM pavelj@mail.nih.gov FU Division of Intramural Research Programs; National Institutes of Mental Health; National Institutes of Health; Department of Health and Human Services, USA FX This study was supported by the Division of Intramural Research Programs, National Institutes of Mental Health, National Institutes of Health, Department of Health and Human Services, USA. NR 46 TC 25 Z9 25 U1 0 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0006-8993 J9 BRAIN RES JI Brain Res. PD DEC 30 PY 2008 VL 1246 BP 111 EP 122 DI 10.1016/j.brainres.2008.09.099 PG 12 WC Neurosciences SC Neurosciences & Neurology GA 396NE UT WOS:000262597600013 PM 18976642 ER PT J AU Kim, PK Hailey, DW Mullen, RT Lippincott-Schwartz, J AF Kim, Peter Kijun Hailey, Dale Warren Mullen, Robert Thomas Lippincott-Schwartz, Jennifer TI Ubiquitin signals autophagic degradation of cytosolic proteins and peroxisomes SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE autophagy; p62; pexophagy ID HANSENULA-POLYMORPHA; MEMBRANE-PROTEIN; SELECTIVE DEGRADATION; FLUORESCENT PROTEINS; CELLS; PATHWAY; MITOCHONDRIA; PROTEOLYSIS; BIOGENESIS; PEXOPHAGY AB Autophagy is responsible for nonspecific, bulk degradation of cytoplasmic components. Recent work has revealed also that there is specific, autophagic degradation of polyubiquitinated protein aggregates, whose buildup occurs during neurodegenerative disease. Here, we report that simple mono-ubiquitination of normally long-lived cytoplasmic substrates is sufficient to target these substrates for autophagic degradation in mammalian cells. That is, upon their ubiquitination, both small [i.e., red fluorescent protein (RFP)] and large ( i.e., peroxisomes) substrates are efficiently targeted to autophagosomes and then degraded within lysosomes upon autophagosome-lysosome fusion. This targeting requires the ubiquitin-binding protein, p62, and is blocked by the Class III phosphatidylinositol 3-kinase (PI3K) inhibitor, 3-methyladenine (3-MA), or by depletion of the autophagy-related-12 (Atg12) protein homolog. Mammalian cells thus use a common pathway involving ubiquitin and p62 for targeting diverse types of substrates for autophagy. C1 [Kim, Peter Kijun; Hailey, Dale Warren; Lippincott-Schwartz, Jennifer] NICHHD, Cell Biol & Metab Program, NIH, Bethesda, MD 20892 USA. [Mullen, Robert Thomas] Univ Guelph, Dept Mol & Cellular Biol, Guelph, ON N1G 2W1, Canada. RP Lippincott-Schwartz, J (reprint author), NICHHD, Cell Biol & Metab Program, NIH, Bethesda, MD 20892 USA. EM lippincj@mail.nih.gov FU National Institutes of Health; Natural Sciences and Engineering Research Council of Canada FX We thank Dr. Satinder Gidda ( University of Guelph) for assistance with the construction of PEX3-GFP-UBko and UBko-RFP. This work was supported by grants from the National Institutes of Health ( to J.L.-S.) and the Natural Sciences and Engineering Research Council of Canada ( to R. T. M.). NR 49 TC 262 Z9 267 U1 4 U2 23 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 30 PY 2008 VL 105 IS 52 BP 20567 EP 20574 DI 10.1073/pnas.0810611105 PG 8 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 389LB UT WOS:000262092800003 PM 19074260 ER PT J AU Lam, LT Davis, RE Ngo, VN Lenz, G Wright, G Xu, WH Zhao, H Yu, X Dang, LN Staudt, LM AF Lam, Lloyd T. Davis, R. Eric Ngo, Vu N. Lenz, Georg Wright, George Xu, Weihong Zhao, Hong Yu, Xin Dang, Lenny Staudt, Louis M. TI Compensatory IKK alpha activation of classical NF-kappa B signaling during IKK beta inhibition identified by an RNA interference sensitization screen SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE Ikka; Ikkb; Nf-kB; RNAi ID T-CELL-ACTIVATION; GENE-EXPRESSION; NF-KAPPA-B2 P100; KINASE-ACTIVITY; DEFICIENT MICE; PHOSPHORYLATION; LYMPHOMA; CARMA1; PATHWAYS; COMPLEX AB A subtype of diffuse large B- cell lymphoma (DLBCL), termed activated B- cell- like (ABC) DLBCL, depends on constitutive nuclear factor-kappa B (NF-kappa B) signaling for survival. Small molecule inhibitors of I kappa B kinase beta(IKK beta), a key regulator of the NF-kappa B pathway, kill ABC DLBCL cells and hold promise for the treatment of this lymphoma type. We conducted an RNA interference genetic screen to investigate potential mechanisms of resistance of ABC DLBCL cells to IKK beta inhibitors. We screened a library of small hairpin RNAs (shRNAs) targeting 500 protein kinases for shRNAs that would increase the killing of an ABC DLBCL cell line in the presence of a small molecule IKK beta inhibitor. Two independent shRNAs targeting IKK alpha synergized with the IKK beta inhibitor to kill three different ABC DLBCL cell lines but were not toxic by themselves. Surprisingly, IKK alpha shRNAs blocked the classical rather than the alternative NF-kappa B pathway in ABC DLBCL cells, as judged by inhibition of I kappa B alpha phosphorylation. IKK alpha shRNA toxicity was reversed by coexpression of wild-type but not kinase inactive forms of IKK alpha, suggesting that IKK alpha may directly phosphorylate I kappa B alpha under conditions of IKK beta inhibition. In models of physiologic NF-kappa B pathway activation by CARD11 or tumor necrosis factor-alpha, compensatory IKK alpha activity was also observed with IKK alpha inhibition. These results suggest that therapy for ABC DLBCL may be improved by targeting both IKK alpha and IKK alpha, possibly through CARD11 inhibition. C1 [Lam, Lloyd T.; Davis, R. Eric; Ngo, Vu N.; Lenz, Georg; Xu, Weihong; Zhao, Hong; Yu, Xin; Staudt, Louis M.] NCI, Metab Branch, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. [Wright, George] NCI, Biometr Res Branch, Rockville, MD 20892 USA. [Dang, Lenny] Millennium Pharmaceut Inc, Cambridge, MA 02139 USA. RP Staudt, LM (reprint author), 9000 Rockville Pike,Bldg 10,Room 4N114, Bethesda, MD 20892 USA. EM lstaudt@mail.nih.gov RI Lenz, Georg/I-6844-2012 FU National Institutes of Health; National Cancer Institute; Center for Cancer Research; German Research Foundation (DFG) FX This research was supported by the Intramural Research Program of the National Institutes of Health, National Cancer Institute, Center for Cancer Research. G. L was also supported by a research grant from the German Research Foundation (DFG). We thank members of the Staudt laboratory for helpful discussions, and Kathleen Meyer for her assistance with GEO submissions. NR 41 TC 55 Z9 58 U1 2 U2 17 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD DEC 30 PY 2008 VL 105 IS 52 BP 20798 EP 20803 DI 10.1073/pnas.0806491106 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 389LB UT WOS:000262092800043 PM 19104039 ER PT J AU Piatigorsky, J AF Piatigorsky, Joram TI Evolution of mollusc lens crystallins: Glutathione S-transferase/S-crystallins and aldehyde dehydrogenase/ohm-crystallins SO AMERICAN MALACOLOGICAL BULLETIN LA English DT Article; Proceedings Paper CT Symposium on Molluscan Models - Advancing our Understanding of the Eye CY JUL 15-20, 2007 CL Antwerp, BELGIUM SP Natl Sci Fdn, Amer Malacol Soc DE cephalopods; scallops; enzymes; lens proteins; eye; gene expression ID EYE LENS; OMEGA-CRYSTALLIN; DETOXIFICATION ENZYMES; CUBOMEDUSAN JELLYFISH; CONVERGENT EVOLUTION; STRUCTURAL PROTEIN; GENE-EXPRESSION; ETA-CRYSTALLIN; SCALLOP LENS; OCTOPUS LENS AB Diverse crystallins (abundant water-soluble proteins) are responsible for the optical properties of transparent cellular eye lenses and are multifunctional proteins that have been recruited from stress proteins and enzymes by enhanced lens expression. The major (S-crystallins) and minor (ohm-crystallin) cephalopod crystallins were recruited from glutathione S-transferase (GST) and aldehyde dehydrogenase (ALDH), respectively, S-crystallins underwent multiple gene duplications while ohm-crystallin appears to be encoded in a single- copy gene. Except for one S-crystallin (considered a "molecular fossil"), S-crystallins lack enzyme activity due to mutation and insertion of a variable central peptide by exon shuffling. The ohm-crystallin is the sole crystallin in scallops. Scallop ohm-crystallin does not bind the co-factor NAD(+/)NADH, lacks enzyme activity, and is a tetramer but migrates as a dimer by gel filtration, suggesting structural adaptations for crystallin function. Similar transcription factors (Pax6 among others) appear to drive high lens expression of crystallin genes in molluscs and other species consistent with convergent recruitment of the non-homologous crystallin genes. C1 NEI, NIH, Mol & Dev Biol Lab, Bethesda, MD 20892 USA. RP Piatigorsky, J (reprint author), NEI, NIH, Mol & Dev Biol Lab, 7 Mem Dr,Bldg 7,Room 100, Bethesda, MD 20892 USA. EM joramp@nei.nih.gov NR 65 TC 3 Z9 3 U1 1 U2 14 PU AMER MALACOLOGICAL SOC, INC PI WILMINGTON PA DELAWARE MUSEUM NATURAL HISTORY, BOX 3937, WILMINGTON, DE 19807-0937 USA SN 0740-2783 EI 2162-2698 J9 AM MALACOL BULL JI Am. Malacol. Bull. PD DEC 29 PY 2008 VL 26 IS 1-2 BP 73 EP 81 DI 10.4003/006.026.0208 PG 9 WC Marine & Freshwater Biology; Zoology SC Marine & Freshwater Biology; Zoology GA 387PC UT WOS:000261963100008 ER PT J AU Ratnayaka, K Faranesh, AZ Guttman, MA Kocaturk, O Saikus, CE Lederman, RJ AF Ratnayaka, Kanishka Faranesh, Anthony Z. Guttman, Michael A. Kocaturk, Ozgur Saikus, Christina E. Lederman, Robert J. TI Interventional cardiovascular magnetic resonance: still tantalizing SO JOURNAL OF CARDIOVASCULAR MAGNETIC RESONANCE LA English DT Review ID RADIOFREQUENCY ABLATION LESIONS; GUIDED PERCUTANEOUS ANGIOPLASTY; ARTERY STENT PLACEMENT; VENA-CAVA FILTER; PULMONARY VASCULAR-RESISTANCE; RESOLUTION INTRAVASCULAR MRI; PASSIVE CATHETER TRACKING; CONGENITAL HEART-DISEASE; ATRIAL SEPTAL-DEFECTS; REAL-TIME MRI AB The often touted advantages of MR guidance remain largely unrealized for cardiovascular interventional procedures in patients. Many procedures have been simulated in animal models. We argue these opportunities for clinical interventional MR will be met in the near future. This paper reviews technical and clinical considerations and offers advice on how to implement a clinical-grade interventional cardiovascular MR (iCMR) laboratory. We caution that this reflects our personal view of the "state of the art." C1 [Ratnayaka, Kanishka; Faranesh, Anthony Z.; Guttman, Michael A.; Kocaturk, Ozgur; Saikus, Christina E.; Lederman, Robert J.] NHLBI, Translat Med Branch, Div Intramural Res, NIH, Bethesda, MD USA. [Ratnayaka, Kanishka] Childrens Natl Med Ctr, Div Cardiol, Washington, DC 20010 USA. RP Lederman, RJ (reprint author), NHLBI, Translat Med Branch, Div Intramural Res, NIH, Bethesda, MD USA. EM ratnayakak@nhlbi.nih.gov; faranesa@nhlbi.nih.gov; guttmanm@nhlbi.nih.gov; Kocaturko@nhlbi.nih.gov; saikusc@nhlbi.nih.gov; lederman@nih.gov RI Kocaturk, Ozgur/A-1419-2016; OI lederman, robert/0000-0003-1202-6673 FU Division of Intramural Research, National Heart Lung and Blood Institute, National Institutes of Health, USA FX Supported by the Division of Intramural Research, National Heart Lung and Blood Institute, National Institutes of Health, USA. NR 165 TC 33 Z9 33 U1 0 U2 2 PU BIOMED CENTRAL LTD PI LONDON PA CURRENT SCIENCE GROUP, MIDDLESEX HOUSE, 34-42 CLEVELAND ST, LONDON W1T 4LB, ENGLAND SN 1097-6647 J9 J CARDIOVASC MAGN R JI J. Cardiov. Magn. Reson. PD DEC 29 PY 2008 VL 10 AR 62 DI 10.1186/1532-429X-10-62 PG 23 WC Cardiac & Cardiovascular Systems; Radiology, Nuclear Medicine & Medical Imaging SC Cardiovascular System & Cardiology; Radiology, Nuclear Medicine & Medical Imaging GA 409WD UT WOS:000263535600001 PM 19114017 ER PT J AU Houzet, L Yeung, ML de Lame, V Desai, D Smith, SM Jeang, KT AF Houzet, Laurent Yeung, Man Lung de Lame, Valery Desai, Dhara Smith, Stephen M. Jeang, Kuan-Teh TI MicroRNA profile changes in human immunodeficiency virus type 1 (HIV-1) seropositive individuals SO RETROVIROLOGY LA English DT Article ID EXPRESSION PROFILES; CELLULAR MICRORNAS; GENE-EXPRESSION; INFECTION; CELLS; REPLICATION; PATHOGENESIS; MODULATION; ACTIVATION; APOPTOSIS AB MicroRNAs ( miRNAs) play diverse roles in regulating cellular and developmental functions. We have profiled the miRNA expression in peripheral blood mononuclear cells from 36 HIV-1 seropositive individuals and 12 normal controls. The HIV-1-positive individuals were categorized operationally into four classes based on their CD4+ T-cell counts and their viral loads. We report that specific miRNA signatures can be observed for each of the four classes. C1 [Houzet, Laurent; Yeung, Man Lung; Jeang, Kuan-Teh] NIAID, Mol Virol Sect, Mol Microbiol Lab, NIH, Bethesda, MD 20892 USA. [de Lame, Valery; Desai, Dhara; Smith, Stephen M.] St Michaels Hosp, Dept Infect Dis, Newark, NJ 07102 USA. RP Jeang, KT (reprint author), NIAID, Mol Virol Sect, Mol Microbiol Lab, NIH, Bethesda, MD 20892 USA. EM houzetl@niaid.nih.gov; yeungm@niaid.nih.gov; delame.lab@gmail.com; desai.dhara@gmail.com; SSmith1824@aol.com; kjeang@niaid.nih.gov RI Jeang, Kuan-Teh/A-2424-2008 FU NIH Bench-to-Bedside Program; Intramural AIDS Targeted Anti-viral Program (IATAP); NIAID; NIH FX This study was supported in part by the NIH Bench-to-Bedside Program, the Intramural AIDS Targeted Anti-viral Program (IATAP), and intramural funding from NIAID, NIH. We thank the NIAID microarray core facility for advice and assistance. NR 41 TC 119 Z9 122 U1 0 U2 5 PU BIOMED CENTRAL LTD PI LONDON PA CURRENT SCIENCE GROUP, MIDDLESEX HOUSE, 34-42 CLEVELAND ST, LONDON W1T 4LB, ENGLAND SN 1742-4690 J9 RETROVIROLOGY JI Retrovirology PD DEC 29 PY 2008 VL 5 AR 118 DI 10.1186/1742-4690-5-118 PG 9 WC Virology SC Virology GA 412OB UT WOS:000263733000001 PM 19114009 ER PT J AU Rajesh, M Mukhopadhyay, P Hasko, G Pacher, P AF Rajesh, Mohanraj Mukhopadhyay, Partha Hasko, Gyoergy Pacher, Pal TI Cannabinoid CB1 receptor inhibition decreases vascular smooth muscle migration and proliferation SO BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS LA English DT Article DE Cannabinoid receptors; Vascular smooth muscle; Proliferation; Migration; Atherosclerosis; Endocannabinoids; Rimonabant; Restenosis ID GROWTH-FACTOR; ENDOCANNABINOID SYSTEM; PHARMACOLOGICAL INHIBITION; CELL-PROLIFERATION; TNF-ALPHA; ATHEROSCLEROSIS; DISEASE; RIMONABANT; MECHANISM; APOPTOSIS AB Vascular smooth muscle proliferation and migration triggered by inflammatory stimuli and chemoattractants such as platelet-derived growth factor (PDGF) are key events in the development and progression of atherosclerosis and restenosis. Cannabinoids may modulate cell proliferation and migration in various cell types through cannabinoid receptors. Here we investigated the effects of CB1 receptor antagonist rimonabant (SR141716A), which has recently been shown to have anti-atherosclerotic effects both in mice and humans, on PDGF-induced proliferation, migration, and signal transduction of human coronary artery smooth Muscle cells (HCASMCs). PDGF induced Ras and ERK 1/2 activation, while increasing proliferation and migration of HCASMCs, which were dose dependently attenuated by CB1 antagonist, rimonabant. These findings suggest that in addition to improving plasma lipid alterations and decreasing inflammatory cell migration and inflammatory response, CB1 antagonists may exert beneficial effects in atherosclerosis and restenosis by decreasing Vascular smooth muscle proliferation and migration. Published by Elsevier Inc. C1 [Rajesh, Mohanraj; Mukhopadhyay, Partha; Pacher, Pal] NIAAA, Lab Physiol Studies, NIH, Sect Oxidat Stress & Tissue Injury, Bethesda, MD 20892 USA. [Hasko, Gyoergy] Univ Med & Dent New Jersey, New Jersey Med Sch, Dept Surg, Newark, NJ 07103 USA. RP Pacher, P (reprint author), NIAAA, Lab Physiol Studies, NIH, Sect Oxidat Stress & Tissue Injury, 5625 Fishers Lane,MSC 9413, Bethesda, MD 20892 USA. EM pacher@mail.nih.gov RI MUKHOPADHYAY, PARTHA/G-3890-2010; Pacher, Pal/B-6378-2008 OI MUKHOPADHYAY, PARTHA/0000-0002-1178-1274; Pacher, Pal/0000-0001-7036-8108 FU NIH FX This publication was supported by Intramural Research Program of NIH. The authors declare no conflicting financial interests. NR 24 TC 27 Z9 27 U1 0 U2 0 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0006-291X J9 BIOCHEM BIOPH RES CO JI Biochem. Biophys. Res. Commun. PD DEC 26 PY 2008 VL 377 IS 4 BP 1248 EP 1252 DI 10.1016/j.bbrc.2008.10.159 PG 5 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 382UM UT WOS:000261630900043 PM 18996082 ER PT J AU Thangudu, RR Manoharan, M Srinivasan, N Cadet, F Sowdhamini, R Offmann, B AF Thangudu, Ratna R. Manoharan, Malini Srinivasan, N. Cadet, Frederic Sowdhamini, R. Offmann, Bernard TI Analysis on conservation of disulphide bonds and their structural features in homologous protein domain families SO BMC STRUCTURAL BIOLOGY LA English DT Article ID AMINO-ACID-COMPOSITION; X-RAY-STRUCTURE; CRYSTAL-STRUCTURE; CONNECTIVITY PREDICTION; GLOBULAR-PROTEINS; ESCHERICHIA-COLI; SUBCELLULAR-LOCALIZATION; EVOLUTIONARY INFORMATION; 3-DIMENSIONAL STRUCTURE; ANGSTROM RESOLUTION AB Background: Disulphide bridges are well known to play key roles in stability, folding and functions of proteins. Introduction or deletion of disulphides by site-directed mutagenesis have produced varying effects on stability and folding depending upon the protein and location of disulphide in the 3-D structure. Given the lack of complete understanding it is worthwhile to learn from an analysis of extent of conservation of disulphides in homologous proteins. We have also addressed the question of what structural interactions replaces a disulphide in a homologue in another homologue. Results: Using a dataset involving 34,752 pairwise comparisons of homologous protein domains corresponding to 300 protein domain families of known 3-D structures, we provide a comprehensive analysis of extent of conservation of disulphide bridges and their structural features. We report that only 54% of all the disulphide bonds compared between the homologous pairs are conserved, even if, a small fraction of the non-conserved disulphides do include cytoplasmic proteins. Also, only about one fourth of the distinct disulphides are conserved in all the members in protein families. We note that while conservation of disulphide is common in many families, disulphide bond mutations are quite prevalent. Interestingly, we note that there is no clear relationship between sequence identity between two homologous proteins and disulphide bond conservation. Our analysis on structural features at the sites where cysteines forming disulphide in one homologue are replaced by non-Cys residues show that the elimination of a disulphide in a homologue need not always result in stabilizing interactions between equivalent residues. Conclusion: We observe that in the homologous proteins, disulphide bonds are conserved only to a modest extent. Very interestingly, we note that extent of conservation of disulphide in homologous proteins is unrelated to the overall sequence identity between homologues. The non-conserved disulphides are often associated with variable structural features that were recruited to be associated with differentiation or specialisation of protein function. C1 [Manoharan, Malini; Sowdhamini, R.] Natl Ctr Biol Sci, Bangalore, Karnataka, India. [Thangudu, Ratna R.; Cadet, Frederic; Offmann, Bernard] Univ Reunion, Lab Biochim & Genet Mol, St Denis 97715 09, Reunion. [Srinivasan, N.] Indian Inst Sci, Mol Biophys Unit, Bangalore 560012, Karnataka, India. [Thangudu, Ratna R.] US Natl Lib Med, Natl Ctr Biotechnol Informat, Bethesda, MD 20894 USA. RP Offmann, B (reprint author), Natl Ctr Biol Sci, GKVK Campus, Bangalore, Karnataka, India. EM thangudr@ncbi.nlm.nih.gov; malinim@ncbs.res.in; ns@mbu.iisc.ernet.in; frederic.cadet@univ-reunion.fr; mini@ncbs.res.in; bernard.offmann@univ-reunion.fr FU Conseil Regional de La Reunion FX RRT was supported by a PhD grant from the Conseil Regional de La Reunion. NS and RS thank the authorities of Universit de La Reunion for their visiting professorships. We thank Dr. Alexandre G. de Brevern for useful comments. NR 100 TC 18 Z9 18 U1 1 U2 25 PU BIOMED CENTRAL LTD PI LONDON PA CURRENT SCIENCE GROUP, MIDDLESEX HOUSE, 34-42 CLEVELAND ST, LONDON W1T 4LB, ENGLAND SN 1471-2237 J9 BMC STRUCT BIOL JI BMC Struct. Biol. PD DEC 26 PY 2008 VL 8 AR 55 DI 10.1186/1472-6807-8-55 PG 22 WC Biophysics SC Biophysics GA 407BC UT WOS:000263337600001 PM 19111067 ER PT J AU Chu, G Yang, W AF Chu, Gilbert Yang, Wei TI Here Comes the Sun: Recognition of UV-Damaged DNA SO CELL LA English DT Editorial Material ID UBIQUITIN LIGASE; REPAIR; PROTEIN; LESION AB The first step in the repair of DNA damage is lesion detection. In this issue, Scrima et al. (2008) report the structure of the complex of DNA Damage-Binding Protein 1 (DDB1) and DDB2 bound to a DNA photodimer, providing critical insight into the repair of DNA damage caused by ultraviolet light. C1 [Yang, Wei] NIDDKD, Mol Biol Lab, NIH, Bethesda, MD 20892 USA. [Chu, Gilbert] Stanford Univ, Med Ctr, Dept Med, Div Oncol, Stanford, CA 94305 USA. [Chu, Gilbert] Stanford Univ, Med Ctr, Dept Biochem, Div Oncol, Stanford, CA 94305 USA. RP Yang, W (reprint author), NIDDKD, Mol Biol Lab, NIH, Bethesda, MD 20892 USA. EM wei.yang@nih.gov RI Yang, Wei/D-4926-2011 OI Yang, Wei/0000-0002-3591-2195 NR 9 TC 7 Z9 7 U1 2 U2 5 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 0092-8674 J9 CELL JI Cell PD DEC 26 PY 2008 VL 135 IS 7 BP 1172 EP 1174 DI 10.1016/j.cell.2008.12.015 PG 3 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 387ZJ UT WOS:000261989800009 PM 19109889 ER PT J AU Bashkirov, PV Akimov, SA Evseev, AI Schmid, SL Zimmerberg, J Frolov, VA AF Bashkirov, Pavel V. Akimov, Sergey A. Evseev, Alexey I. Schmid, Sandra L. Zimmerberg, Joshua Frolov, Vadim A. TI GTPase Cycle of Dynamin Is Coupled to Membrane Squeeze and Release, Leading to Spontaneous Fission SO CELL LA English DT Article ID DEPENDENT CONFORMATIONAL-CHANGES; BIOLOGICAL-MEMBRANES; NERVE-TERMINALS; ENDOCYTOSIS; CURVATURE; VESICLES; TENSION; FUSION; DOMAIN; CELLS AB The GTPase dynamin is critically involved in membrane fission during endocytosis. How does dynamin use the energy of GTP hydrolysis for membrane remodeling? By monitoring the ionic permeability through lipid nanotubes (NT), we found that dynamin was capable of squeezing NT to extremely small radii, depending on the NT lipid composition. However, long dynamin scaffolds did not produce fission: instead, fission followed GTPase-dependent cycles of assembly and disassembly of short dynamin scaffolds and involved a stochastic process dependent on the curvature stress imposed by dynamin. Fission happened spontaneously upon NT release from the scaffold, without leakage. Our calculations revealed that local narrowing of NT could induce cooperative lipid tilting, leading to self-merger of the inner monolayer of NT (hemifission), consistent with the absence of leakage. We propose that dynamin transmits GTP's energy to periodic assembling of a limited curvature scaffold that brings lipids to an unstable intermediate. C1 [Bashkirov, Pavel V.; Akimov, Sergey A.; Zimmerberg, Joshua; Frolov, Vadim A.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Program Phys Biol, Bethesda, MD 20892 USA. [Bashkirov, Pavel V.; Akimov, Sergey A.; Evseev, Alexey I.] Russian Acad Sci, AN Frumkin Inst Phys Chem & Electrochem, Moscow 119991, Russia. [Schmid, Sandra L.] Scripps Res Inst, Dept Cell Biol, La Jolla, CA 92037 USA. RP Zimmerberg, J (reprint author), Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Program Phys Biol, Bethesda, MD 20892 USA. EM joshz@mail.nih.gov RI Bashkirov, Pavel/J-2385-2012; Akimov, Sergey/L-2001-2013; Akimov, Sergey/I-6432-2015; OI Frolov, Vadim/0000-0002-0653-5669 FU National Institutes of Health (NIH) [R01GM42455, R37MH61345]; RFBR [08-04-00085]; CRDF GAP [RUB1-1297(5)-MO-05]; Russian Federal Agency for Science and Innovations [02.512.11.0010]; Program of Molecular and Cellular Biology RAS; Leading Scientific Schools of Russian Federation [4181.2008.4] FX This work was partially supported by the National Institutes of Health (NIH) intramural program (NICHD), and grants NIH R01GM42455 and R37MH61345, RFBR 08-04-00085, and CRDF GAP RUB1-1297(5)-MO-05, Russian Federal Agency for Science and Innovations 02.512.11.0010, Program of Molecular and Cellular Biology RAS, and the grant for State Support of Leading Scientific Schools of Russian Federation 4181.2008.4. The BODIPY-labeled dynamin was generously provided by Rajesh Ramachandran. We are grateful to Vladimir Lizunov and Gennady Kushnir for their technical help and Thomas Pucadyil, Anna Shnyrova, and Yuri Chizmadzhev for a careful reading of the manuscript and fruitful discussions. NR 42 TC 164 Z9 166 U1 1 U2 25 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 0092-8674 J9 CELL JI Cell PD DEC 26 PY 2008 VL 135 IS 7 BP 1276 EP 1286 DI 10.1016/j.cell.2008.11.028 PG 11 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 387ZJ UT WOS:000261989800018 PM 19084269 ER PT J AU Franco, R DeHaven, WI Sifre, MI Bortner, CD Cidlowski, JA AF Franco, Rodrigo DeHaven, Wayne I. Sifre, Maria I. Bortner, Carl D. Cidlowski, John A. TI Glutathione Depletion and Disruption of Intracellular Ionic Homeostasis Regulate Lymphoid Cell Apoptosis SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID MITOCHONDRIAL PERMEABILITY TRANSITION; PLASMA-MEMBRANE DEPOLARIZATION; FAS-MEDIATED APOPTOSIS; CYTOCHROME-C RELEASE; REDUCED GLUTATHIONE; OXIDATIVE STRESS; K+ CHANNELS; VOLUME DECREASE; T-LYMPHOCYTES; POTASSIUM CHANNELS AB Intracellular glutathione (GSH) depletion is an important hallmark of apoptosis. We have recently shown that GSH depletion by its extrusion regulates apoptosis independently of excessive reactive oxygen species accumulation. However, the mechanisms by which GSH depletion regulates apoptosis are still unclear. Because disruption of intracellular ionic homeostasis, associated with apoptotic volume decrease (AVD), is necessary for the progression of apoptotic cell death, we sought to evaluate the relationship between GSH transport and ionic homeostasis during Fas ligand (FasL)-induced apoptosis in Jurkat cells. GSH depletion in response to FasL was paralleled by distinct degrees of AVD identified by differences in cellular forward scatter and electronic impedance analysis. Inhibition of GSH efflux prevented AVD, K(+) loss, and the activation of two distinct ionic conductances, mediated by Kv1.3 and outward rectifying Cl(-) channels. Reciprocally, stimulation of GSH loss accelerated the loss of K(+), AVD, and consequently the progression of the execution phase of apoptosis. Although high extracellular K(+) inhibited FasL-induced apoptosis, GSH depletion was largely independent of K(+) loss. These results suggest that deregulation of GSH and ionic homeostasis converge in the regulation of apoptosis in lymphoid cells. C1 [Franco, Rodrigo; DeHaven, Wayne I.; Sifre, Maria I.; Bortner, Carl D.; Cidlowski, John A.] NIEHS, Lab Signal Transduct, NIH, Res Triangle Pk, NC 27709 USA. RP Cidlowski, JA (reprint author), NIEHS, Lab Signal Transduct, NIH, POB 12233,111 TW Alexander Dr, Res Triangle Pk, NC 27709 USA. EM cidlows1@mail.nih.gov RI Franco, Rodrigo/D-9470-2013 OI Franco, Rodrigo/0000-0003-3241-8615 FU National Institutes of Health grant FX This work was supported, in whole or in part, by a National Institutes of Health grant (intramural research program of the NIEHS). The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked "advertisement" in accordance with 18 U. S. C. Section 1734 solely to indicate this fact. NR 97 TC 27 Z9 28 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 26 PY 2008 VL 283 IS 52 BP 36071 EP 36087 DI 10.1074/jbc.M807061200 PG 17 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 385VA UT WOS:000261840500003 PM 18940791 ER PT J AU Dvir-Ginzberg, M Gagarina, V Lee, EJ Hall, DJ AF Dvir-Ginzberg, Mona Gagarina, Viktoria Lee, Eun-Jin Hall, David J. TI Regulation of Cartilage-specific Gene Expression in Human Chondrocytes by SirT1 and Nicotinamide Phosphoribosyltransferase SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID TRANSCRIPTIONAL COACTIVATOR PGC-1-ALPHA; HISTONE DEACETYLASE INHIBITORS; II COLLAGEN GENE; CELL-SURVIVAL; SOX9; CHONDROGENESIS; PROTEIN; CHROMATIN; COMPLEX; MUSCLE AB SirT1 is an NAD-dependent histone deacetylase that regulates gene expression, differentiation, development, and organism life span. Here we investigate the function of SirT1 in human chondrocytes derived from osteoarthritic patients. Elevation of SirT1 protein levels or activity in these chondrocytes led to a dramatic increase in cartilage-specific gene expression, whereas a reduction in SirT1 levels or activity significantly lowered cartilage gene expression. SirT1 associated with the cartilage-specific transcription factor Sox9, enhancing transcription from the collagen 2(alpha 1) promoter in a Sox9-dependent fashion. Consistent with this association, SirT1 was targeted to the collagen 2(alpha 1) enhancer and promoter, which in turn recruited the coactivators GCN5, PGC1 alpha, and p300. This led to elevated marks of active chromatin within the promoter; that is, acetylated histone K9/K14 and histone H4K5 as well as trimethylated histone H3K4. Finally, alterations in the NAD salvage pathway enzyme nicotinamide phosphoribosyltransferase led to changes in NAD levels, SirT activity, and cartilage-specific gene expression in human chondrocytes. SirT1, nicotinamide phosphoribosyltransferase, and NAD may, therefore, provide a positive function in human cartilage by elevating expression of genes encoding cartilage extracellular matrix. C1 [Dvir-Ginzberg, Mona; Gagarina, Viktoria; Lee, Eun-Jin; Hall, David J.] NIAMS, Cartilage Mol Genet Grp, Cartilage Biol & Orthopaed Branch, NIH, Bethesda, MD 20892 USA. RP Hall, DJ (reprint author), 50 South Dr,Rm 1524, Bethesda, MD 20892 USA. EM halld@mail.nih.gov OI Dvir-Ginzberg, Mona/0000-0003-3089-6875 FU National Institutes of Health FX This work was supported, in whole or in part, by the National Institutes of Health (Intramural Research Program of the NIAMS). The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked "advertisement" in accordance with 18 U. S. C. Section 1734 solely to indicate this fact. NR 47 TC 86 Z9 92 U1 0 U2 5 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD DEC 26 PY 2008 VL 283 IS 52 BP 36300 EP 36310 DI 10.1074/jbc.M803196200 PG 11 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 385VA UT WOS:000261840500026 PM 18957417 ER PT J AU Hazelwood, LA Free, RB Cabrera, DM Skinbjerg, M Sibley, DR AF Hazelwood, Lisa A. Free, R. Benjamin Cabrera, David M. Skinbjerg, Mette Sibley, David R. TI Reciprocal Modulation of Function between the D-1 and D-2 Dopamine Receptors and the Na+, K+-ATPase SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID PROTEIN-KINASE-C; PLASMA-MEMBRANE; NA+,K+-ATPASE ENDOCYTOSIS; INTERACTING PROTEINS; D1; DESENSITIZATION; RECRUITMENT; PHOSPHORYLATION; NA,K-ATPASE; INHIBITION AB It is well documented that dopamine can increase or decrease the activity of the Na+, K+-ATPase (NKA, sodium pump) in an organ-specific fashion. This regulation can occur, at least partially, via receptor-mediated second messenger activation and can promote NKA insertion or removal from the plasma membrane. Using co-immunoprecipitation and mass spectrometry, we now show that, in both brain and HEK293T cells, D-1 and D-2 dopamine receptors (DARs) can exist in a complex with the sodium pump. To determine the impact of NKA on DAR function, biological assays were conducted with NKA and DARs co-expressed in HEK293T cells. In this system, expression of NKA dramatically decreased D-1 and D-2 DAR densities with a concomitant functional decrease in DAR-mediated regulation of cAMP levels. Interestingly, pharmacological inhibition of endogenous or overexpressed NKA enhanced DAR function without altering receptor number or localization. Similarly, DAR function was also augmented by small interfering RNA reduction of the endogenous NKA. These data suggest that, under basal conditions, NKA negatively regulates DAR function via protein-protein interactions. In reciprocal fashion, expression of DARs decreases endogenous NKA function in the absence of dopamine, implicating DAR proteins as regulators of NKA activity. Notably, dopamine stimulation or pertussis toxin inhibition of D-2 receptor signaling did not alter NKA activity, indicating that the D-2-mediated decrease in NKA function is dependent upon protein-protein interactions rather than signaling molecules. This evidence for reciprocal regulation between DARs and NKA provides a novel control mechanism for both DAR signaling and cellular ion balance. C1 [Hazelwood, Lisa A.; Free, R. Benjamin; Cabrera, David M.; Skinbjerg, Mette; Sibley, David R.] NINDS, Mol Neuropharmacol Sect, NIH, Bethesda, MD 20892 USA. RP Sibley, DR (reprint author), NINDS, Mol Neuropharmacol Sect, NIH, 5625 Fishers Ln,Rm 4S-04,MSC 9405, Bethesda, MD 20852 USA. EM sibley@helix.nih.gov RI Cabrera, David/I-1013-2014 FU National Institutes of Health FX This work was supported, in whole or in part, by National Institutes of Health grant (Intramural Research Program of NINDS). The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked "advertisement" in accordance with 18 U. S. C. Section 1734 solely to indicate this fact. NR 36 TC 23 Z9 26 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 26 PY 2008 VL 283 IS 52 BP 36441 EP 36453 DI 10.1074/jbc.M805520200 PG 13 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 385VA UT WOS:000261840500042 PM 18984584 ER PT J AU Tessmer, I Yang, Y Zhai, J Du, CW Hsieh, P Hingorani, MM Erie, DA AF Tessmer, Ingrid Yang, Yong Zhai, Jie Du, Chungwei Hsieh, Peggy Hingorani, Manju M. Erie, Dorothy A. TI Mechanism of MutS Searching for DNA Mismatches and Signaling Repair SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID ESCHERICHIA-COLI MUTS; THERMUS-AQUATICUS; CRYSTAL-STRUCTURE; DAMAGE RECOGNITION; ATPASE ACTIVITY; PROTEIN MUTS; MINOR-GROOVE; BINDING; HYDROLYSIS; DOMAINS AB DNA mismatch repair is initiated by the recognition of mismatches by MutS proteins. The mechanism by which MutS searches for and recognizes mismatches and subsequently signals repair remains poorly understood. We used single-molecule analyses of atomic force microscopy images of MutS-DNA complexes, coupled with biochemical assays, to determine the distributions of conformational states, the DNA binding affinities, and the ATPase activities of wild type and two mutants of MutS, with alanine substitutions in the conserved Phe-Xaa-Glu mismatch recognition motif. We find that on homoduplex DNA, the conserved Glu, but not the Phe, facilitates MutS-induced DNA bending, whereas at mismatches, both Phe and Glu promote the formation of an unbent conformation. The data reveal an unusual role for the Phe residue in that it promotes the unbending, not bending, of DNA at mismatch sites. In addition, formation of the specific unbent MutS-DNA conformation at mismatches appears to be required for the inhibition of ATP hydrolysis by MutS that signals initiation of repair. These results provide a structural explanation for the mechanism by which MutS searches for and recognizes mismatches and for the observed phenotypes of mutants with substitutions in the Phe-Xaa-Glu motif. C1 [Tessmer, Ingrid; Yang, Yong; Erie, Dorothy A.] Univ N Carolina, Dept Chem, Chapel Hill, NC 27599 USA. [Erie, Dorothy A.] Univ N Carolina, Curriculum Appl Sci & Engn, Chapel Hill, NC 27599 USA. [Du, Chungwei; Hsieh, Peggy] NIDDK, NIH, Bethesda, MD 20892 USA. [Zhai, Jie; Hingorani, Manju M.] Wesleyan Univ, Dept Biochem & Mol Biol, Middletown, CT 06459 USA. RP Erie, DA (reprint author), Univ N Carolina, Dept Chem, CB 3290, Chapel Hill, NC 27599 USA. EM derie@unc.edu FU National Institutes of Health [GM079480]; American Cancer Society [RSG03- 047-04-GMC]; National Science Foundation [0448379]; Intramural Research Program of NIDDK FX This work was supported, in whole or in part, by National Institutes of Health Grant GM079480 (to D.A.E.). This work was also supported by Grant RSG03- 047-04-GMC from the American Cancer Society (to D.A.E.), National Science Foundation Grant MCB 0448379 (to M.M.H.), and the Intramural Research Program of NIDDK (to P.H. and C.D.). The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked "advertisement" in accordance with 18 U. S. C. Section 1734 solely to indicate this fact. NR 48 TC 28 Z9 28 U1 1 U2 12 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD DEC 26 PY 2008 VL 283 IS 52 BP 36646 EP 36654 DI 10.1074/jbc.M805712200 PG 9 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 385VA UT WOS:000261840500063 PM 18854319 ER PT J AU Willard, FS Zheng, Z Guo, J Digby, GJ Kimple, AJ Conley, JM Johnston, CA Bosch, D Willard, MD Watts, VJ Lambert, NA Ikeda, SR Du, QS Siderovski, DP AF Willard, Francis S. Zheng, Zhen Guo, Juan Digby, Gregory J. Kimple, Adam J. Conley, Jason M. Johnston, Christopher A. Bosch, Dustin Willard, Melinda D. Watts, Val J. Lambert, Nevin A. Ikeda, Stephen R. Du, Quansheng Siderovski, David P. TI A Point Mutation to G alpha(i) Selectively Blocks GoLoco Motif Binding DIRECT EVIDENCE FOR G alpha.GoLoco COMPLEXES IN MITOTIC SPINDLE DYNAMICS SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID ASYMMETRIC CELL-DIVISION; HETEROTRIMERIC G-PROTEIN; DISSOCIATION INHIBITOR ACTIVITY; G-ALPHA-I; CAENORHABDITIS-ELEGANS EMBRYOS; VOLTAGE-DEPENDENT MODULATION; GUANINE-NUCLEOTIDE EXCHANGE; RAT SYMPATHETIC NEURONS; ENDOGENOUS RGS PROTEINS; BETA-GAMMA-SUBUNITS AB Heterotrimeric G-protein G alpha subunits and GoLoco motif proteins are key members of a conserved set of regulatory proteins that influence invertebrate asymmetric cell division and vertebrate neuroepithelium and epithelial progenitor differentiation. GoLoco motif proteins bind selectively to the inhibitory subclass (G alpha(i)) of G alpha subunits, and thus it is assumed that a G alpha(i.)GoLoco motif protein complex plays a direct functional role in microtubule dynamics underlying spindle orientation and metaphase chromosomal segregation during cell division. To address this hypothesis directly, we rationally identified a point mutation to G alpha(i) subunits that renders a selective loss-of-function for GoLoco motif binding, namely an asparagine-to-isoleucine substitution in the alpha D-alpha E loop of the G alpha helical domain. This GoLoco-insensitivity ("GLi") mutation prevented G alpha(i1) association with all human GoLoco motif proteins and abrogated interaction between the Caenorhabditis elegans G alpha sub-unit GOA-1 and the GPR-1 GoLoco motif. In contrast, the GLi mutation did not perturb any other biochemical or signaling properties of G alpha(i) subunits, including nucleotide binding, intrinsic and RGS protein-accelerated GTP hydrolysis, and interactions with G beta gamma dimers, adenylyl cyclase, and seven transmembrane-domain receptors. GoLoco insensitivity rendered G alpha(i) subunits unable to recruit GoLoco motif proteins such as GPSM2/LGN and GPSM3 to the plasma membrane, and abrogated the exaggerated mitotic spindle rocking normally seen upon ectopic expression of wild type G alpha(i) subunits in kidney epithelial cells. This GLi mutation should prove valuable in establishing the physiological roles of G alpha(i).GoLoco motif protein complexes in microtubule dynamics and spindle function during cell division as well as to delineate potential roles for GoLoco motifs in receptor-mediated signal transduction. C1 [Willard, Francis S.; Kimple, Adam J.; Johnston, Christopher A.; Bosch, Dustin; Willard, Melinda D.; Siderovski, David P.] Univ N Carolina, Dept Pharmacol, Chapel Hill, NC 27599 USA. [Siderovski, David P.] Univ N Carolina, Lineberger Comprehens Canc Ctr, Chapel Hill, NC 27599 USA. [Siderovski, David P.] Univ N Carolina, Ctr Neurosci, Chapel Hill, NC 27599 USA. [Zheng, Zhen; Du, Quansheng] Med Coll Georgia, Inst Mol Med & Genet, Dept Neurol, Augusta, GA 30912 USA. [Digby, Gregory J.; Lambert, Nevin A.] Med Coll Georgia, Inst Mol Med & Genet, Dept Pharmacol & Toxicol, Augusta, GA 30912 USA. [Guo, Juan; Ikeda, Stephen R.] NIAAA, Lab Mol Physiol, Bethesda, MD 20892 USA. [Conley, Jason M.; Watts, Val J.] Purdue Univ, Dept Med Chem & Mol Pharmacol, W Lafayette, IN 47906 USA. RP Willard, FS (reprint author), Eli Lilly & Co, Lilly Res Labs, Indianapolis, IN 46285 USA. EM willardfs@lilly.com RI Watts, Val/A-4633-2012; OI Ikeda, Stephen/0000-0002-4088-9508 FU National Institutes of Health [R01 GM074268, GM079506, GM078319, MH060397, F32 GM07694, F30 MH074266]; NIAAA intramural program; American Cancer Society [RSG0717601CSM]; National Science Foundation [0620024]; American Heart Association; PhRMA Foundation FX This work was supported, in whole or in part, by National Institutes of Health Grants R01 GM074268 (to D.P.S.), GM079506 (to Q.D.), GM078319 (to N.A.L.), MH060397 (to V.J.W.), F32 GM07694 (to C.A.J.), and F30 MH074266 (to A.J.K.). This work was also supported by the NIAAA intramural program (to S. R. I.), American Cancer Society Grant RSG0717601CSM (to Q.D.), National Science Foundation Grant MCB 0620024 (to N.A.L.), and fellowships from the American Heart Association (to G.J.D.) and the PhRMA Foundation (to M.D.W.). The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked "advertisement" in accordance with 18 U. S. C. Section 1734 solely to indicate this fact. NR 80 TC 28 Z9 34 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 26 PY 2008 VL 283 IS 52 BP 36698 EP 36710 DI 10.1074/jbc.M804936200 PG 13 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 385VA UT WOS:000261840500068 PM 18984596 ER PT J AU Weisberg, RA AF Weisberg, Robert A. TI Transcription by Moonlight: Structural Basis of an Extraribosomal Activity of Ribosomal Protein S10 SO MOLECULAR CELL LA English DT Editorial Material ID ANTITERMINATION COMPLEX; TERMINATION; LAMBDA; REGION C1 NIH, Bethesda, MD 20892 USA. RP Weisberg, RA (reprint author), NIH, Bldg 37,Room 5138, Bethesda, MD 20892 USA. EM rweisberg@nih.gov FU Intramural NIH HHS [Z01 HD000066-37] NR 10 TC 16 Z9 16 U1 0 U2 0 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 26 PY 2008 VL 32 IS 6 BP 747 EP 748 DI 10.1016/j.molcel.2008.12.010 PG 2 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 390SO UT WOS:000262184200001 PM 19111651 ER PT J AU Luo, X Hsiao, HH Bubunenko, M Weber, G Court, DL Gottesman, ME Urlaub, H Wahl, MC AF Luo, Xiao Hsiao, He-Hsuan Bubunenko, Mikhail Weber, Gert Court, Donald L. Gottesman, Max E. Urlaub, Henning Wahl, Markus C. TI Structural and Functional Analysis of the E. coli NusB-S10 Transcription Antitermination Complex SO MOLECULAR CELL LA English DT Article ID LAMBDA-N-PROTEIN; RIBOSOMAL-RNA TRANSCRIPTION; ESCHERICHIA-COLI; MYCOBACTERIUM-TUBERCULOSIS; BACTERIOPHAGE-LAMBDA; ANGSTROM RESOLUTION; CRYSTAL-STRUCTURE; PHAGE-LAMBDA; FACTOR-NUSA; BINDING AB Protein S10 is a component of the 30S ribosomal subunit and participates together with NusB protein in processive transcription antitermination. The molecular mechanisms by which S10 can act as a translation or a transcription factor are not understood. We used complementation assays and recombineering to delineate regions of S10 dispensable for antitermination, and determined the crystal structure of a transcriptionally active NusB-S10 complex. In this complex, S10 adopts the same fold as in the 30S subunit and is blocked from simultaneous association with the ribosome. Mass spectrometric mapping of UV-induced crosslinks revealed that the NusB-S10 complex presents an intermolecular, composite, and contiguous binding surface for RNAs containing BoxA antitermination signals. Furthermore, S10 overproduction complemented a nusB null phenotype. These data demonstrate that S10 and NusB together form a BoxA-binding module, that NusB facilitates entry of S10 into the transcription machinery, and that S10 represents a central hub in processive antitermination. C1 [Gottesman, Max E.] Columbia Univ, Med Ctr, Dept Microbiol & Biochem, New York, NY 10032 USA. [Gottesman, Max E.] Columbia Univ, Med Ctr, Dept Mol Biophys, New York, NY 10032 USA. [Luo, Xiao; Weber, Gert; Wahl, Markus C.] Max Planck Inst Biophys Chem, Res Grp Xray Crystallog, D-37077 Gottingen, Germany. [Hsiao, He-Hsuan; Urlaub, Henning] Max Planck Inst Biophys Chem, Res Grp Bioanalyt Mass Spectrometry, D-37077 Gottingen, Germany. [Bubunenko, Mikhail; Court, Donald L.] NCI, Gene Regulat & Chromosomal Biol Lab, Ctr Canc Res, Frederick, MD 21702 USA. [Bubunenko, Mikhail] NCI, Basic Res Program, SAIC Frederick Inc, Frederick, MD 21702 USA. [Wahl, Markus C.] Univ Gottingen, Dept Med, D-37077 Gottingen, Germany. RP Gottesman, ME (reprint author), Columbia Univ, Med Ctr, Dept Microbiol & Biochem, New York, NY 10032 USA. EM meg8@columbia.edu; mwahl@gwdg.de RI Weber, Gert/I-1800-2013; Wahl, Markus/D-6365-2017 OI Wahl, Markus/0000-0002-2811-5307 FU Deutsche Forschungsgemeinschaft [WA 1126/3-1]; National Institutes of Health (NIH) [GM37219] FX We thank Elke Penka and Monika Raabe (Max-Planck-institute for Biophysical Chemistry, Gdttingen, Germany) for excellent technical assistance, the staff at beamlines PXI/II (SLS, Villigen, Switzerland) and BL14.2 (BESSY, Berlin, Germany) for support during diffraction data collection, and Andrew Byrd and Amanda Altieri (NCI, Frederick, MID, USA) for communication of results prior to publication. M.C.W. was supported by grant WA 1126/3-1 from the Deutsche Forschungsgemeinschaft. M.E.G. was supported by National Institutes of Health (NIH) grant GM37219. H.U. was supported by a young invest!gatorgrant ofEURASNET. Thisresearch wassupported in part by the Intramural Research Program of the NIH, National Cancer Institute, Center for Cancer Research, and by a Trans NIH/FDA Intramural Biodefense Program Grant from MAID to D.L.C. This project was funded in part with federal funds from the National Cancer Institute, National Institutes of Health, under contract N01CO-12400. The content of this publication does not necessarily reflect the views or policies of the Department of Health and Human Services, nor does mention of trade names, commercial products, or organizations imply endorsement by the U.S. government. The authors declare that they have no competing financial interests. NR 51 TC 51 Z9 51 U1 0 U2 6 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 26 PY 2008 VL 32 IS 6 BP 791 EP 802 DI 10.1016/j.molcel.2008.10.028 PG 12 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 390SO UT WOS:000262184200009 PM 19111659 ER PT J AU Pelkey, KA Topolnik, L Yuan, XQ Lacaille, JC McBain, CJ AF Pelkey, Kenneth A. Topolnik, Lisa Yuan, Xiao-Qing Lacaille, Jean-Claude McBain, Chris J. TI State-Dependent cAMP Sensitivity of Presynaptic Function Underlies Metaplasticity in a Hippocampal Feedforward Inhibitory Circuit SO NEURON LA English DT Article ID LONG-TERM POTENTIATION; METABOTROPIC GLUTAMATE RECEPTORS; BIDIRECTIONAL SYNAPTIC PLASTICITY; FIBER-INTERNEURON SYNAPSES; DIVERGENT RELEASE SITES; VISUAL-CORTEX; RAT HIPPOCAMPUS; CYCLIC-AMP; IN-VIVO; LTP AB At hippocampal mossy fiber (MF)-st. lucidum interneuron (SLIN) synapses, mGluR7 serves as a metaplastic switch controlling bidirectional plasticity. mGluR7 activation during high-frequency stimulation (HFS) triggers presynaptic LTD due to persistent P/Q-type Ca(2+) channel inhibition. However, following mGluR7 internalization HFS produces presynaptic LTP. Surprisingly, LTP is not a simple molecular reversal of Ca(2+) channel depression. Rather, mGluR7 activation/internalization controls plasticity polarity by gating cAMP sensitivity of release. While naive surface mGluR7 expressing MF-SLIN synapses are insensitive to cAMP elevation, synapses that have internalized mGluR7 robustly potentiate following cAMP increases. Moreover, MF-SLIN LTP requires adenylate cyclase (AC) and protein kinase A (PKA) activities. We also discovered an association between mGluR7 and RIM1 alpha, an active zone molecule required for AC/PKA-dependent presynaptic LTP. Importantly, the mGluR7-RIM1 alpha interaction is regulated by mGluR7 activation, and mice lacking RIM1 alpha are deficient in MF-SLIN LTP. We conclude that state-dependent cAMP sensitivity controlled by mGluR7-RIM1 alpha interactions underlies MF-SLIN metaplasticity. C1 [Pelkey, Kenneth A.; Yuan, Xiao-Qing; McBain, Chris J.] NICHHD, Lab Cellular & Synapt Neurophysiol, NIH, Bethesda, MD 20892 USA. [Topolnik, Lisa; Lacaille, Jean-Claude] Univ Montreal, Dept Physiol, Grp Rech Syst Nerveux Cent, Montreal, PQ H3C 3J7, Canada. RP Pelkey, KA (reprint author), NICHHD, Lab Cellular & Synapt Neurophysiol, NIH, Bldg 35, Bethesda, MD 20892 USA. EM pelkeyk2@mail.nih.gov; mcbainc@mail.nih.gov FU NIH; Savoy Foundation FX The authors thank Brian Jeffries for expert technical assistance and Richard Robitaille for expertise and guidance with two-photon confocal imaging. Myc-mGluR7a/b constructs were a generous gift from Drs. Laurent Fagni and Frederica Bertaso. Affinity-purified mGluR7b antibody was kindly provided by Drs. Katherine Roche and Young Ho Suh. We are very grateful to Drs. Tom Sudhof and Pascal Kaeser for providing RIM1 alpha mice. This work was supported by an NICHD intramural award to C.J.M., CIHR and FRSO awards to J.-C.L., and an HFSP award to both C.J.M. and J.-C.L. J.-C.L. is the recipient of the Canada Research Chair in Cellular and Molecular Neurophysiology. K.A.P. is an NIH Fellow. L.T. was supported by the Savoy Foundation. NR 43 TC 36 Z9 36 U1 1 U2 2 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 0896-6273 J9 NEURON JI Neuron PD DEC 26 PY 2008 VL 60 IS 6 BP 980 EP 987 DI 10.1016/j.neuron.2008.11.018 PG 8 WC Neurosciences SC Neurosciences & Neurology GA 391BW UT WOS:000262208900007 PM 19109906 ER PT J AU Kriegeskorte, N Mur, M Ruff, DA Kiani, R Bodurka, J Esteky, H Tanaka, K Bandettini, PA AF Kriegeskorte, Nikolaus Mur, Marieke Ruff, Douglas A. Kiani, Roozbeh Bodurka, Jerzy Esteky, Hossein Tanaka, Keiji Bandettini, Peter A. TI Matching Categorical Object Representations in Inferior Temporal Cortex of Man and Monkey SO NEURON LA English DT Article ID INFEROTEMPORAL CORTEX; HUMAN BRAIN; CEREBRAL-CORTEX; VISUAL-CORTEX; RESPONSE PATTERNS; SINGLE NEURONS; FMRI ACTIVITY; FACE AREA; PRIMATE; RECOGNITION AB Inferior temporal (IT) object representations have been intensively studied in monkeys and humans, but representations of the same particular objects have never been compared between the species. Moreover, IT's role in categorization is not well understood. Here, we presented monkeys and humans with the same images of real-world objects and measured the IT response pattern elicited by each image. In order to relate the representations between the species and to computational models, we compare response-pattern dissimilarity matrices. IT response patterns form category clusters, which match between man and monkey. The clusters correspond to animate and inanimate objects; within the animate objects, faces and bodies form subclusters. Within each category, IT distinguishes individual exemplars, and the within-category exemplar similarities also match between the species. Our findings suggest that primate IT across species may host a common code, which combines a categorical and a continuous representation of objects. C1 [Kriegeskorte, Nikolaus; Mur, Marieke; Ruff, Douglas A.; Bodurka, Jerzy; Bandettini, Peter A.] NIMH, Sect Funct Imaging Methods, Lab Brain & Cognit, NIH, Bethesda, MD 20892 USA. [Mur, Marieke] Maastricht Univ, Fac Psychol, Dept Cognit Neurosci, NL-6229 ER Maastricht, Netherlands. [Kiani, Roozbeh] Univ Washington, Dept Neurobiol & Behav, Seattle, WA 98195 USA. [Bodurka, Jerzy; Bandettini, Peter A.] NIMH, Funct Magnet Resonance Imaging Facil, NIH, Bethesda, MD 20892 USA. [Esteky, Hossein] Shahid Beheshti Univ, Sch Med, Res Grp Brain & Cognit Sci, Tehran, Iran. [Esteky, Hossein] Inst Studies Theoret Phys & Math, Sch Cognit Sci, Tehran, Iran. [Tanaka, Keiji] RIKEN Brain Sci Inst, Cognit Brain Mapping Lab, Wako, Saitama 3510198, Japan. RP Kriegeskorte, N (reprint author), NIMH, Sect Funct Imaging Methods, Lab Brain & Cognit, NIH, Bethesda, MD 20892 USA. EM kriegeskorten@mail.nih.gov RI Tanaka, Keiji/N-5917-2015; OI Kriegeskorte, Nikolaus/0000-0001-7433-9005; Ruff, Douglas/0000-0001-7228-8822 FU Intramural Program of the National Institute of Mental Health FX We thank Chris Baker, James Haxby, Alex Martin, Nancy Kanwisher, Dwight Kravitz, Leslie Ungerleider. and Vina Vo for helpful discussions. This research was supported in part by the Intramural Program of the National Institute of Mental Health. NR 70 TC 353 Z9 358 U1 9 U2 51 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 0896-6273 J9 NEURON JI Neuron PD DEC 26 PY 2008 VL 60 IS 6 BP 1126 EP 1141 DI 10.1016/j.neuron.2008.10.043 PG 16 WC Neurosciences SC Neurosciences & Neurology GA 391BW UT WOS:000262208900017 PM 19109916 ER PT J AU Barinka, C Byun, Y Dusich, CL Banerjee, SR Chen, Y Castanares, M Kozikowski, AP Mease, RC Pomper, MG Lubkowski, J AF Barinka, Cyril Byun, Youngjoo Dusich, Crystal L. Banerjee, Sangeeta R. Chen, Ying Castanares, Mark Kozikowski, Alan P. Mease, Ronnie C. Pomper, Martin G. Lubkowski, Jacek TI Interactions between Human Glutamate Carboxypeptidase II and Urea-Based Inhibitors: Structural Characterization SO JOURNAL OF MEDICINAL CHEMISTRY LA English DT Article ID NAAG PEPTIDASE INHIBITORS; MEMBRANE ANTIGEN; PROSTATE-CANCER; N-ACETYLASPARTYLGLUTAMATE; SUBSTRATE-SPECIFICITY; ACTIVE-SITE; NAALADASE; THERAPY; DESIGN; EXPRESSION AB Urea-based, low molecular weight ligands of glutamate carboxypeptidase II (GCPII) have demonstrated efficacy in various models of neurological disorders and call serve as imaging agents for prostate cancer. To enhance further development of such compounds, we determined X-ray structures Of four complexes between human GCPII and urea-based inhibitors at high resolution. All ligands demonstrate in invariant glutarate moiety within the S1' pocket of the enzyme. The Ureido linkage between P1 and P1' inhibitor sites interacts with the active-site Zn(1)(2+) ion and the side chains of Tyr552 and His553. Interactions within the S I pocket are defined primarily by a network of hydrogen bonds between the P1 carboxylate group of the inhibitors and the side chains of Arg534, Arg536, and Asn519. Importantly, we have identified a hydrophobic pocket accessory to the S1 site that call be exploited for structure-based design of novel GCPII inhibitors with increased lipophilicity. C1 [Barinka, Cyril; Lubkowski, Jacek] NCI, Ctr Canc Res, Frederick, MD 21702 USA. [Castanares, Mark; Pomper, Martin G.] Johns Hopkins Med Inst, Dept Pharmacol & Mol Sci, Baltimore, MD 21231 USA. [Kozikowski, Alan P.] Univ Illinois, Dept Med Chem & Pharmacognosy, Chicago, IL 60612 USA. [Byun, Youngjoo; Dusich, Crystal L.; Banerjee, Sangeeta R.; Chen, Ying; Mease, Ronnie C.; Pomper, Martin G.] Johns Hopkins Med Inst, Russell H Morgan Dept Radiol & Radiol Sci, Baltimore, MD 21231 USA. RP Pomper, MG (reprint author), NCI, Macromol Crystallog Lab, 539 Boyles St, Frederick, MD 21702 USA. EM mpomper@jhmi.edu; jacek@ncifcrf.gov RI Barinka, Cyril/G-9803-2014 FU Intramural NIH HHS; NCI NIH HHS [CA1114111, CA111982, CA92871]; NIBIB NIH HHS [EB005423]; NIMH NIH HHS [MH080580] NR 41 TC 56 Z9 58 U1 0 U2 19 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 25 PY 2008 VL 51 IS 24 BP 7737 EP 7743 DI 10.1021/jm800765e PG 7 WC Chemistry, Medicinal SC Pharmacology & Pharmacy GA 386IH UT WOS:000261876400011 PM 19053759 ER PT J AU Kurimura, M Liu, H Sulima, A Hashimoto, A Przybyl, AK Ohshima, E Kodato, S Deschamps, JR Dersch, CM Rothman, RB Lee, YS Jacobson, AE Rice, KC AF Kurimura, Muneaki Liu, Hehua Sulima, Agnieszka Hashimoto, Akihiro Przybyl, Anna K. Ohshima, Etsuo Kodato, Shinichi Deschamps, Jeffrey R. Dersch, Christina M. Rothman, Richard B. Lee, Yong Sok Jacobson, Arthur E. Rice, Kenner C. TI Probes for Narcotic Receptor Mediated Phenomena. 37.(1) Synthesis and Opioid Binding Affinity of the Final Pair of Oxide-Bridged Phenylmorphans, the Ortho- and Para-b-Isomers and Their N-Phenethyl Analogues, and the Synthesis of the N-Phenethyl Analogues of the Ortho- and Para-d-Isomers SO JOURNAL OF MEDICINAL CHEMISTRY LA English DT Article ID PROTEIN-COUPLED RECEPTORS; AGONIST DELTA-ANTAGONIST; FORCED-SWIM TEST; 5-(META-HYDROXYPHENYL)MORPHAN AB In the isomeric series of 12 racemic topologically rigid N-methyl analogues of oxide-bridged phenylmorphans, all but two of the racemates, the ortho- and para-b-oxide-bridged phenylmorphans 20 and 12, have remained to be synthesized. The b-isomers were very difficult to synthesize because of the highly strained 5,6-transfused ring junction that had to be formed. Our successful strategy required functionalization of the position para (or ortho) to a fluorine atom on the aromatic ring using an electron-withdrawing nitro group to activate that fluorine. The racemic N-phenethyl analogues 24 and 16 were moderately potent K-receptor antagonists in the [S-35]GTP gamma S assay. We synthesized the N-phenethyl-substituted oxide-bridged phenylmorphans in the ortho- and para-d-oxide-bridged phenylmorphan series (51 and 52) which had not been previously evaluated using contemporary receptor binding assays to see whether they also have higher affinity for opioid receptors than their N-methyl relatives 46 and 47. C1 [Kurimura, Muneaki; Liu, Hehua; Sulima, Agnieszka; Hashimoto, Akihiro; Przybyl, Anna K.; Ohshima, Etsuo; Kodato, Shinichi; Jacobson, Arthur E.; Rice, Kenner C.] NIDA, Drug Design & Synth Sect, Chem Biol Res Branch, Bethesda, MD 20892 USA. [Kurimura, Muneaki; Liu, Hehua; Sulima, Agnieszka; Hashimoto, Akihiro; Przybyl, Anna K.; Ohshima, Etsuo; Kodato, Shinichi; Jacobson, Arthur E.; Rice, Kenner C.] NIAAA, NIH, Dept Hlth & Human Serv, Bethesda, MD 20892 USA. [Dersch, Christina M.; Rothman, Richard B.] NIDA, Clin Psychopharmacol Sect, Chem Biol Res Branch, Addict Res Ctr,Natl Inst Hlth,Dept Hlth & Human S, Baltimore, MD 21224 USA. [Lee, Yong Sok] NIH, Ctr Mol Modeling, Div Computat Biosci, CIT,DHHS, Bethesda, MD 20892 USA. [Deschamps, Jeffrey R.] USN, Res Lab, Struct Matter Lab, Washington, DC 20375 USA. RP Rice, KC (reprint author), NIDA, Drug Design & Synth Sect, Chem Biol Res Branch, 5625 Fishers Lane,Room 4N03, Bethesda, MD 20892 USA. EM kr21f@nih.gov FU Intramural NIH HHS [Z99 DA999999]; NIDA NIH HHS [Y01 DA006002] NR 21 TC 15 Z9 15 U1 0 U2 6 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 25 PY 2008 VL 51 IS 24 BP 7866 EP 7881 DI 10.1021/jm800913d PG 16 WC Chemistry, Medicinal SC Pharmacology & Pharmacy GA 386IH UT WOS:000261876400024 PM 19053757 ER PT J AU Andrei, D Maciag, AE Chakrapani, H Citro, ML Keefer, LK Saavedra, JE AF Andrei, Daniela Maciag, Anna E. Chakrapani, Harinath Citro, Michael L. Keefer, Larry K. Saavedra, Joseph E. TI Aryl Bis(diazeniumdiolates): Potent Inducers of S-Glutathionylation of Cellular Proteins and Their in Vitro Antiproliferative Activities SO JOURNAL OF MEDICINAL CHEMISTRY LA English DT Article ID NITRIC-OXIDE PRODRUGS; JS-K; ANTICANCER LEAD; LEUKEMIA-CELLS; ANTILEUKEMIC ACTIVITY; SIGNALING MOLECULE; SECONDARY-AMINES; REDOX REGULATION; RELAXING FACTOR; DONOR AB A number of bis(diazeniumdiolates) that we designed to release up to 4 mol of nitric oxide (NO) and that are structural analogues of the NO prodrug and anticancer lead compound O(2)-{2,4-dinitro-5-[4-(N-methylamino)benzoyloxy]phenyl} 1-(N,N-dimethylamino)diazen-1-ium-1,2-diolate (PABA/NO) were synthesized and studied. A majority of these compounds yielded higher levels of NO, were better inhibitors of proliferation of a number of cancer cell lines, and more rapidly induced substantially increased levels of S-glutathionylation of cellular proteins in comparison with PABA/NO. In most cases, the antiproliferative activity and extents of S-glutathionylation correlated well with levels of intracellular NO release. We report bis(diazeniumdiolates) to be a class of S-glutathionylating agents with potent antiproliferative and S-glutathionylating activity. C1 [Maciag, Anna E.; Citro, Michael L.; Saavedra, Joseph E.] Natl Canc Inst Frederick, SAIC Frederick, Basic Res Program, Ft Detrick, MD 21702 USA. [Andrei, Daniela; Chakrapani, Harinath; Keefer, Larry K.] Natl Canc Inst Frederick, Chem Sect, Comparat Carcinogenesis Lab, Ft Detrick, MD 21702 USA. RP Andrei, D (reprint author), Dominican Univ, Dept Chem, 7900 W Div St, River Forest, IL 60305 USA. EM dandrei@dorn.edu; keefer@ncifcrf.gov RI Keefer, Larry/N-3247-2014 OI Keefer, Larry/0000-0001-7489-9555 FU NIH; Intramural Research Program of the NIH; National Cancer Institute; Center for Cancer Research; National Cancer Institute [N01-CO-12400] FX This research was supported by the Intramural Research Program of the NIH, National Cancer Institute, Center for Cancer Research, as well as by National Cancer Institute Contract N01-CO-12400 to SAIC-Frederick. NR 45 TC 17 Z9 18 U1 1 U2 6 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 25 PY 2008 VL 51 IS 24 BP 7944 EP 7952 DI 10.1021/jm800831y PG 9 WC Chemistry, Medicinal SC Pharmacology & Pharmacy GA 386IH UT WOS:000261876400031 PM 19053760 ER PT J AU Jiang, JK Ghoreschi, K Deflorian, F Chen, Z Perreira, M Pesu, M Smith, J Nguyen, DT Liu, EH Leister, W Costanzi, S O'Shea, JJ Thomas, CJ AF Jiang, Jian-Kang Ghoreschi, Kamran Deflorian, Francesca Chen, Zhi Perreira, Melissa Pesu, Marko Smith, Jeremy Nguyen, Dac-Trung Liu, Eric H. Leister, William Costanzi, Stefano O'Shea, John J. Thomas, Craig J. TI Examining the Chirality, Conformation and Selective Kinase Inhibition of 3-((3R,4R)-4-methyl-3-(methyl(7H-pyrrolo[2,3-d]pyrimidin-4-yl)amino)pipe ridin-1-yl)-3-oxopropanenitrile (CP-690,550) SO JOURNAL OF MEDICINAL CHEMISTRY LA English DT Article ID TYROSINE PHOSPHORYLATION; JANUS KINASE-3; JAK3; ACTIVATION AB Here, we examine the significance that stereochemistry plays within the clinically relevant Janus kinase 3 (Jak3) inhibitor 1 (CP-690,550). A synthesis of all four enantiopure stereoisomers of the drug was carried out and an examination of each compound revealed that only the enantiopure 3R,4R isomer was capable of blocking Stat5 phosphorylation (Jak3 dependent). Each compound was profiled across a panel of over 350 kinases, which revealed a high level of selectivity for the Jak family kinases for these related compounds. Each stereoisomer retained a degree of binding to Jak3 and Jak2 and the 3R,4S and 3S,4R stereoisomers were further revealed to have binding affinity for selected members of the STE7 and STE20 subfamily of kinases. finally, an appraisal of the minimum energy conformation of each stereoisomer and molecular docking at Jak3 was performed in an effort to better understand each compounds selectivity and potency profiles. C1 [Jiang, Jian-Kang; Perreira, Melissa; Nguyen, Dac-Trung; Leister, William; Thomas, Craig J.] NHGRI, NIH, Chem Genom Ctr, Bethesda, MD 20892 USA. [Ghoreschi, Kamran; Chen, Zhi; Pesu, Marko; O'Shea, John J.] NIAMSD, Mol Immunol & Inflammat Branch, NIH, Rockville, MD 20850 USA. [Deflorian, Francesca; Costanzi, Stefano] NIDDK, Lab Biol Modeling, NIH, Bethesda, MD 20892 USA. [Liu, Eric H.] NIDDK, Transplantat & Autoimmun Branch, NIH, Bethesda, MD 20892 USA. [Smith, Jeremy] Kelly Serv, Rockville, MD 20852 USA. RP Thomas, CJ (reprint author), NHGRI, NIH, Chem Genom Ctr, 9800 Med Ctr Dr,Bldg B,Room 3005,Mail Stop Code 3, Bethesda, MD 20892 USA. EM craigt@nhgri.nih.gov RI Costanzi, Stefano/G-8990-2013; Pesu, marko/L-6344-2013; OI Nguyen, Dac-Trung/0000-0003-2591-9948; Costanzi, Stefano/0000-0003-3183-7332 FU Molecular Libraries Initiative of the National Institutes of Health Roadmap for Medical Research; Intramural Research Program of the National Human Genome Research Institute; National Institute of Arthritis and Musculoskeletal and Skin Diseases; National Institute of Diabetes and Digestive and Kidney Diseases; National Institutes of Health FX We thank Dr. David Maloney and Dr. Douglas Auld for advice and help during the preparation of this manuscript. We thank Allison Peck for critical reading of this manuscript. 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, the National Institute of Arthritis and Musculoskeletal and Skin Diseases, and the National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health. NR 35 TC 62 Z9 65 U1 0 U2 18 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0022-2623 EI 1520-4804 J9 J MED CHEM JI J. Med. Chem. PD DEC 25 PY 2008 VL 51 IS 24 BP 8012 EP 8018 DI 10.1021/jm801142b PG 7 WC Chemistry, Medicinal SC Pharmacology & Pharmacy GA 386IH UT WOS:000261876400037 PM 19053756 ER PT J AU Walkup, JT Albano, AM Piacentini, J Birmaher, B Compton, SN Sherrill, JT Ginsburg, GS Rynn, MA McCracken, J Waslick, B Iyengar, S March, JS Kendall, PC AF Walkup, John T. Albano, Anne Marie Piacentini, John Birmaher, Boris Compton, Scott N. Sherrill, Joel T. Ginsburg, Golda S. Rynn, Moira A. McCracken, James Waslick, Bruce Iyengar, Satish March, John S. Kendall, Philip C. TI Cognitive Behavioral Therapy, Sertraline, or a Combination in Childhood Anxiety SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Article ID RANDOMIZED CLINICAL-TRIAL; PLACEBO-CONTROLLED TRIAL; DISORDERS; CHILDREN; ADOLESCENTS; YOUTH; FLUOXETINE; ADULTHOOD; SAMPLE; RISK AB Background: Anxiety disorders are common psychiatric conditions affecting children and adolescents. Although cognitive behavioral therapy and selective serotonin-reuptake inhibitors have shown efficacy in treating these disorders, little is known about their relative or combined efficacy. Methods: In this randomized, controlled trial, we assigned 488 children between the ages of 7 and 17 years who had a primary diagnosis of separation anxiety disorder, generalized anxiety disorder, or social phobia to receive 14 sessions of cognitive behavioral therapy, sertraline (at a dose of up to 200 mg per day), a combination of sertraline and cognitive behavioral therapy, or a placebo drug for 12 weeks in a 2:2:2:1 ratio. We administered categorical and dimensional ratings of anxiety severity and impairment at baseline and at weeks 4, 8, and 12. Results: The percentages of children who were rated as very much or much improved on the Clinician Global Impression-Improvement scale were 80.7% for combination therapy (P<0.001), 59.7% for cognitive behavioral therapy (P<0.001), and 54.9% for sertraline (P<0.001); all therapies were superior to placebo (23.7%). Combination therapy was superior to both monotherapies (P<0.001). Results on the Pediatric Anxiety Rating Scale documented a similar magnitude and pattern of response; combination therapy had a greater response than cognitive behavioral therapy, which was equivalent to sertraline, and all therapies were superior to placebo. Adverse events, including suicidal and homicidal ideation, were no more frequent in the sertraline group than in the placebo group. No child attempted suicide. There was less insomnia, fatigue, sedation, and restlessness associated with cognitive behavioral therapy than with sertraline. Conclusions: Both cognitive behavioral therapy and sertraline reduced the severity of anxiety in children with anxiety disorders; a combination of the two therapies had a superior response rate. (ClinicalTrials.gov number, NCT00052078.). C1 [Walkup, John T.; Ginsburg, Golda S.] Johns Hopkins Med Inst, Dept Psychiat & Behav Sci, Div Child & Adolescent Psychiat, Baltimore, MD 21287 USA. [Albano, Anne Marie; Rynn, Moira A.] Columbia Univ, Med Ctr, New York State Psychiat Inst, New York, NY USA. [Piacentini, John; McCracken, James] Univ Calif Los Angeles, Los Angeles, CA USA. [Birmaher, Boris; Iyengar, Satish] Univ Pittsburgh, Med Ctr, Western Psychiat Inst & Clin, Pittsburgh, PA USA. [Compton, Scott N.; March, John S.] Duke Univ, Med Ctr, Durham, NC USA. [Sherrill, Joel T.] NIMH, Div Serv & Intervent Res, Bethesda, MD 20892 USA. [Waslick, Bruce] Baystate Med Ctr, Springfield, MA USA. [Kendall, Philip C.] Temple Univ, Philadelphia, PA 19122 USA. RP Walkup, JT (reprint author), Johns Hopkins Med Inst, Dept Psychiat & Behav Sci, Div Child & Adolescent Psychiat, 600 N Wolfe St, Baltimore, MD 21287 USA. RI Piacentini, John/C-4645-2011 FU NIMH NIH HHS [U01 MH064088, K23 MH075843, L40 MH072315, L40 MH072315-02, U01 MH063747, U01 MH064003, U01 MH064089, U01 MH064092, U01 MH064107, U01 MH63747, U01 MH64003, U01 MH64088, U01 MH64092, U01 MH64107] NR 32 TC 432 Z9 435 U1 12 U2 59 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 25 PY 2008 VL 359 IS 26 BP 2753 EP 2766 DI 10.1056/NEJMoa0804633 PG 14 WC Medicine, General & Internal SC General & Internal Medicine GA 387KJ UT WOS:000261950800003 PM 18974308 ER PT J AU Powell, SL Goedecke, T Nikolic, D Chen, SN Ahn, S Dietz, B Farnsworth, NR van Breemen, RB Lankin, DC Pauli, GF Bolton, JL AF Powell, Sharla L. Goedecke, Tanja Nikolic, Dejan Chen, Shao-Nong Ahn, Soyoun Dietz, Birgit Farnsworth, Norman R. van Breemen, Richard B. Lankin, David C. Pauli, Guido F. Bolton, Judy L. TI In Vitro Serotonergic Activity of Black Cohosh and Identification of N-omega-Methylserotonin as a Potential Active Constituent SO JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY LA English DT Article DE Black cohosh; N-methylserotonin; Cimicifuga; menopause; serotonin ID PERFORMANCE LIQUID-CHROMATOGRAPHY; MIXED COMPETITIVE LIGAND; MORPHINE-DEPENDENT RATS; DORSAL RAPHE NUCLEUS; CIMICIFUGA-RACEMOSA; POSTMENOPAUSAL WOMEN; MENOPAUSAL SYMPTOMS; LIGHT-SCATTERING; ACTAEA-RACEMOSA; PARTIAL AGONIST AB Cimicifuga racemosa (L.) Nutt. (syn. Actaea racemosa L., black cohosh) is used to relieve menopausal hot flashes, although clinical studies have provided conflicting data, and the active constituent(s) and mechanism(s) of action remain unknown. Because serotonergic receptors and transporters are involved with thermoregulation, black cohosh and its phytoconstituents were evaluated for serotonergic activity using 5-HT7 receptor binding, cAMP induction, and serotonin selective re-uptake inhibitor (SSRI) assays. Crude extracts displayed 5-HT7 receptor binding activity and induced cAMP production. Fractionation of the methanol extract led to isolation of phenolic acids and identification of N-omega-methylserotonin by LC-MS/MS. Cimicifuga triterpenoids and phenolic acids bound weakly to the 5-HT7 receptor with no cAMP or SSRI activity. In contrast, N-omega-methylserotonin showed 5-HT7 receptor binding (IC50 = 23 pM), induced cAMP (EC50 = 22 nM), and blocked serotonin re-uptake (IC50 = 490 nM). These data suggest N-omega-methylserotonin may be responsible for the serotonergic activity of black cohosh. C1 [Bolton, Judy L.] Univ Illinois, Dept Med Chem & Pharmacognosy, Coll Pharm, Ctr Bot Dietary Supplements Res, Chicago, IL 60612 USA. Univ Illinois, NIH, Coll Pharm, Ctr Bot Dietary Supplements Res, Chicago, IL 60612 USA. RP Bolton, JL (reprint author), Univ Illinois, Dept Med Chem & Pharmacognosy, Coll Pharm, Ctr Bot Dietary Supplements Res, 833 S Wood St,MC 781, Chicago, IL 60612 USA. EM Judy.Bolton@uic.edu RI Godecke, Tanja/G-7384-2011; OI Godecke, Tanja/0000-0001-9188-1613 FU Office of Dietary Supplements (ODS) [P50 AT00155]; National Center for Complementary and Alternative Medicine (NCCAM); Office for Research on Women's Health (ORWH); National Institute of General Medicine (NIGMS) of the National Institutes of Health (NIH); NCCAM [F31 AT 003995] FX This work was supported by Grant P50 AT00155 provided jointly by the Office of Dietary Supplements (ODS), the National Center for Complementary and Alternative Medicine (NCCAM), the Office for Research on Women's Health (ORWH), and the National Institute of General Medicine NIGMS) of the National Institutes of Health (NIH). S.L.P. is grateful for a Ruth L. Kirschstein NCCAM predoctoral fellowship, F31 AT 003995. The contents of this paper are solely the responsibility of the authors and do not necessarily represent the official views of the NIH. NR 47 TC 35 Z9 43 U1 0 U2 4 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 24 PY 2008 VL 56 IS 24 BP 11718 EP 11726 DI 10.1021/jf803298z PG 9 WC Agriculture, Multidisciplinary; Chemistry, Applied; Food Science & Technology SC Agriculture; Chemistry; Food Science & Technology GA 385GJ UT WOS:000261802400024 PM 19049296 ER PT J AU Butterfield, LH Disis, ML Fox, BA Lee, PP Khleif, SN Thurin, M Trinchieri, G Wang, E Wigginton, J Chaussabel, D Coukos, G Dhodapkar, M Hakansson, L Janetzki, S Kleen, TO Kirkwood, JM Maccalli, C Maecker, H Maio, M Malyguine, A Masucci, G Palucka, AK Potter, DM Ribas, A Rivoltini, L Schendel, D Seliger, B Selvan, S Slingluff, CL Stroncek, DF Streicher, H Wu, XF Zeskind, B Zhao, YD Zocca, MB Zwierzina, H Marincola, FM AF Butterfield, Lisa H. Disis, Mary L. Fox, Bernard A. Lee, Peter P. Khleif, Samir N. Thurin, Magdalena Trinchieri, Giorgio Wang, Ena Wigginton, Jon Chaussabel, Damien Coukos, George Dhodapkar, Madhav Hakansson, Leif Janetzki, Sylvia Kleen, Thomas O. Kirkwood, John M. Maccalli, Cristina Maecker, Holden Maio, Michele Malyguine, Anatoli Masucci, Giuseppe Palucka, A. Karolina Potter, Douglas M. Ribas, Antoni Rivoltini, Licia Schendel, Dolores Seliger, Barbara Selvan, Senthamil Slingluff, Craig L., Jr. Stroncek, David F. Streicher, Howard Wu, Xifeng Zeskind, Benjamin Zhao, Yingdong Zocca, Mai-Britt Zwierzina, Heinz Marincola, Francesco M. TI A systematic approach to biomarker discovery; Preamble to "the iSBTc-FDA taskforce on immunotherapy biomarkers" SO JOURNAL OF TRANSLATIONAL MEDICINE LA English DT Editorial Material ID CYTOKINE FLOW-CYTOMETRY; EXPRESSION ANALYSIS; CANCER; CELLS; INTERLEUKIN-2; TETRAMER; ELISPOT; CRYOPRESERVATION; MELANOMA; THERAPY AB The International Society for the Biological Therapy of Cancer (iSBTc) has initiated in collaboration with the United States Food and Drug Administration (FDA) a programmatic look at innovative avenues for the identification of relevant parameters to assist clinical and basic scientists who study the natural course of host/tumor interactions or their response to immune manipulation. The task force has two primary goals: 1) identify best practices of standardized and validated immune monitoring procedures and assays to promote inter-trial comparisons and 2) develop strategies for the identification of novel biomarkers that may enhance our understating of principles governing human cancer immune biology and, consequently, implement their clinical application. Two working groups were created that will report the developed best practices at an NCI/FDA/iSBTc sponsored workshop tied to the annual meeting of the iSBTc to be held in Washington DC in the Fall of 2009. This foreword provides an overview of the task force and invites feedback from readers that might be incorporated in the discussions and in the final document. C1 [Butterfield, Lisa H.; Kirkwood, John M.] Univ Pittsburgh, Dept Med, Div Hematol Oncol, Inst Canc, Pittsburgh, PA 15213 USA. [Disis, Mary L.] Univ Washington, Tumor Vaccine Grp, Ctr Translat Med Womens Hlth, Seattle, WA 98195 USA. [Fox, Bernard A.] Providence Portland Med Ctr, Earle A Chiles Res Inst, Portland, OR 97213 USA. [Fox, Bernard A.] Oregon Hlth & Sci Univ, Dept Mol Biol, Inst Canc, Portland, OR 97213 USA. [Lee, Peter P.] Stanford Univ, Dept Med, Div Hematol, Stanford, CA 94305 USA. [Khleif, Samir N.] NCI, Canc Vaccine Sect, NIH, Bethesda, MD 20892 USA. [Thurin, Magdalena] NCI, Canc Diag Program, Rockville, MD 20852 USA. [Trinchieri, Giorgio] NCI, Canc & Inflammat Program, NIH, Frederick, MD 21702 USA. [Wang, Ena; Marincola, Francesco M.] NIH, IDIS, Dept Transfus Med, Ctr Clin, Bethesda, MD 20892 USA. [Wang, Ena; Marincola, Francesco M.] NIH, Ctr Human Immunol, Bethesda, MD 20892 USA. [Wigginton, Jon] Bristol Myers Squibb Co, Princeton, NJ 08540 USA. [Chaussabel, Damien; Palucka, A. Karolina] Baylor Inst Immunol Res, Dallas, TX 75204 USA. [Chaussabel, Damien; Palucka, A. Karolina] Baylor Res Inst, Dallas, TX 75204 USA. [Coukos, George] Univ Penn, Ctr Res Early Detect & Cure Ovarian Canc, Philadelphia, PA 19104 USA. [Dhodapkar, Madhav] Yale Univ, Dept Hematol, New Haven, CT 06510 USA. [Hakansson, Leif] Lund Univ, Div Clin Tumor Immunol, S-58185 Linkoping, Sweden. [Janetzki, Sylvia] ZellNet Consulting Inc, Ft Lee, NJ 07024 USA. [Kleen, Thomas O.] Cellular Technol Ltd, Shaker Hts, OH 44122 USA. [Maccalli, Cristina] Ist Sci San Raffaele, DIBIT, Unit Immunobiotherapy Solid Tumors, Dept Mol Oncol, I-20132 Milan, Italy. [Maecker, Holden] Baylor Inst Immunol Res, Dallas, TX 75204 USA. [Maio, Michele] Univ Hosp Siena, Ist Toscano Tumori, Dept Oncol, Siena, Italy. [Maio, Michele] IRCCS, Ctr Riferimento Oncol, Dept Med Oncol, Canc Bioimmunotherapy Unit, I-53100 Aviano, Italy. [Malyguine, Anatoli] NCI, SAIC Frederick Inc, Lab Cell Mediated Immun, Frederick, MD 21702 USA. [Masucci, Giuseppe] Karolinska Inst, Dept Oncol Pathol, S-17176 Stockholm, Sweden. [Potter, Douglas M.] Univ Pittsburgh, Grad Sch Publ Hlth, Dept Biostat, Pittsburgh, PA 15213 USA. [Ribas, Antoni] Univ Calif Los Angeles, Dept Med, Jonsson Comprehens Canc Ctr, Los Angeles, CA 90095 USA. [Rivoltini, Licia] Ist Nazl Tumori, IRCCS Fdn, Unit Immunotherapy Human Tumors, I-20100 Milan, Italy. [Schendel, Dolores] German Res Ctr Environm Hlth, Inst Mol Immunol, D-81377 Munich, Germany. [Schendel, Dolores] German Res Ctr Environm Hlth, Clin Cooperat Grp Immune Monitoring, Helmholtz Zentrum Munchen, D-81377 Munich, Germany. [Seliger, Barbara] Univ Halle Wittenberg, Inst Med Immunol, D-06112 Halle, Saale, Germany. [Selvan, Senthamil] Hoag Canc Ctr, Newport Beach, CA 92663 USA. [Slingluff, Craig L., Jr.] Univ Virginia, Sch Med, Div Surg Oncol, Dept Surg, Charlottesville, VA 22908 USA. [Stroncek, David F.] NIH, Cell Therapy Sect, Dept Transfus Med, Ctr Clin, Bethesda, MD 20892 USA. [Streicher, Howard] NCI, Canc Therapy Evaluat Program, Bethesda, MD 20852 USA. [Wu, Xifeng] Univ Texas Houston, MD Anderson Canc Ctr, Dept Epidemiol, Houston, TX 77030 USA. [Zeskind, Benjamin] Immuneering Corp, Boston, MA 02215 USA. [Zhao, Yingdong] NCI, Biometr Res Branch, Bethesda, MD 20852 USA. [Zocca, Mai-Britt] DanDritt Biotech AS, DK-2100 Copenhagen, Denmark. [Zwierzina, Heinz] Innsbruck Med Univ, Dept Internal Med, A-6020 Innsbruck, Austria. RP Butterfield, LH (reprint author), Univ Pittsburgh, Dept Med, Div Hematol Oncol, Inst Canc, Pittsburgh, PA 15213 USA. EM butterfieldl@upmc.edu; ndisis@u.washington.edu; foxb@foxlab.org; ppl@stanford.edu; khleif@nih.gov; thurinm@mail.nih.gov; trinchig@mail.nih.gov; ewang@mail.cc.nih.gov; jon.wigginton@bms.com; damienc@baylorhealth.edu; gcks@med.upenn.edu; dhodapk@rockefeller.edu; Leif.Hakansson@lio.se; sylvia@zellnet.com; thomas.kleen@immunospot.com; kirkwoodjm@upmc.edu; Maccalli.cristina@hsr.it; hmaecker@yahoo.com; mmaio@cro.it; malyguinea@mail.nih.gov; giuseppe.masucci@ki.se; karolinp@BaylorHealth.edu; potter@upci.pitt.edu; ARibas@mednet.ucla.edu; licia.rivoltini@istitutotumori.mi.it; schendel@helmholtz-muenchen.de; Barbara.seliger@meditiu.uni-halle.de; sselvan@hoaghospital.org; CLS8H@virginia.edu; dstroncek@mail.cc.nih.gov; streicherh@mail.nih.gov; xwu@mdanderson.org; bzeskind@immuneering.com; zhaoy@helix.nih.gov; mbz@dandrit.com; Heinz.zwierzina@i-med.ac.at; fmarincola@mail.cc.nih.gov OI Masucci, Giuseppe/0000-0002-9583-2306; coral, sandra/0000-0002-1308-3082; Rivoltini, Licia/0000-0002-2409-6225; Chaussabel, Damien/0000-0002-6131-7242 NR 44 TC 36 Z9 36 U1 0 U2 4 PU BIOMED CENTRAL LTD PI LONDON PA CURRENT SCIENCE GROUP, MIDDLESEX HOUSE, 34-42 CLEVELAND ST, LONDON W1T 4LB, ENGLAND SN 1479-5876 J9 J TRANSL MED JI J. Transl. Med. PD DEC 23 PY 2008 VL 6 AR 81 DI 10.1186/1479-5876-6-81 PG 10 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 409WT UT WOS:000263537200001 PM 19105846 ER PT J AU Mittal, J Hummer, G AF Mittal, Jeetain Hummer, Gerhard TI Static and dynamic correlations in water at hydrophobic interfaces SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE capillary waves; drying transition; hydrophobic effect; surface tension ID SCALED-PARTICLE THEORY; DEWETTING TRANSITION; PERTURBATION-THEORY; MOLECULAR-DYNAMICS; AQUEOUS-SOLUTIONS; LENGTH SCALES; HYDRATION; COLLAPSE; SOLUTES; LIQUID AB We study the static and dynamic properties of the water-density fluctuations in the interface of large nonpolar solutes. With the help of extensive molecular dynamics simulations of TIP4P water near smooth spherical solutes, we show that for large solutes, the interfacial density profile is broadened by capillary waves. For purely repulsive solutes, the squared width of the interface increases linearly with the logarithm of the solute size, as predicted by capillary-wave theory. The apparent interfacial tension extracted from the slope agrees with that of a free liquid-vapor interface. The characteristic length of local density fluctuations is approximate to 0.5 nm, measured along the arc, again consistent with that of a free liquid-vapor interface. Probed locally, the interfacial density fluctuations exhibit large variances that exceed those expected for an ideal gas. Qualitatively consistent with theories of the free liquid-vapor interface, we find that the water interface near large and strongly nonpolar solutes is flickering, broadened by capillary-wave fluctuations. These fluctuations result in transitions between locally wet and dry regions that are slow on a molecular time scale. C1 [Mittal, Jeetain; Hummer, Gerhard] NIDDK, Chem Phys Lab, Natl Inst Hlth, Bethesda, MD 20892 USA. RP Hummer, G (reprint author), NIDDK, Chem Phys Lab, Natl Inst Hlth, Bethesda, MD 20892 USA. EM gerhard.hummer@nih.gov RI Hummer, Gerhard/A-2546-2013 OI Hummer, Gerhard/0000-0001-7768-746X FU National Institutes of Health (NIH); National Institute of Diabetes and Digestive and Kidney Diseases FX J.M. thanks Dr. Artur Adib for several helpful discussions and supporting a postdoctoral fellowship during this work. We also thank Dr. Attila Szabo (National Institutes of Health), Dr. Robert Best (University of Cambridge, Cambridge, U. K.), and Sapna Sarupria (Rensselaer Polytechnic Institute, Troy, NY) for pertinent suggestions. This work was supported by the Intramural Research Program of the National Institutes of Health (NIH), National Institute of Diabetes and Digestive and Kidney Diseases. This study used the high-performance computational capabilities of the Biowulf PC/Linux cluster at the NIH (http://biowulf.nih.gov). NR 66 TC 84 Z9 84 U1 1 U2 44 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 23 PY 2008 VL 105 IS 51 BP 20130 EP 20135 DI 10.1073/pnas.0809029105 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 388BP UT WOS:000261995600025 PM 19074279 ER PT J AU Mittal, J Best, RB AF Mittal, Jeetain Best, Robert B. TI Thermodynamics and kinetics of protein folding under confinement SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE macromolecular crowding; course-grained simulation; energy landscape; diffusion ID MOLECULAR CONFINEMENT; ENERGY LANDSCAPE; STABILITY; SIMULATIONS; DYNAMICS; MODEL; SPACES; RATES; ENHANCEMENT; ENVIRONMENT AB Understanding the effects of confinement on protein stability and folding kinetics is important for describing protein folding in the cellular environment. We have investigated the effects of confinement on two structurally distinct proteins as a function of the dimension d(c) and characteristic size R of the confining boundary. We find that the stabilization of the folded state relative to bulk conditions is quantitatively described by R-gamma c, where the exponent gamma(c) is approximate to 5/3 independent of the dimension of confinement d(c) (cylindrical, planar, or spherical). Moreover, we find that the logarithm of the folding rates also scale as R-gamma c, with deviations only being seen for very small confining geometries, where folding is downhill; for both stability and kinetics, the dominant effect is the change in the free energy of the unfolded state. A secondary effect on the kinetics is a slight destabilization of the transition state by confinement, although the contacts present in the confined transition state are essentially identical to the bulk case. We investigate the effect of confinement on the position-dependent diffusion coefficients D(Q) for dynamics along the reaction coordinate Q (fraction of native contacts). The diffusion coefficients only change in the unfolded state basin, where they are increased because of compaction. C1 [Best, Robert B.] Univ Cambridge, Dept Chem, Cambridge CB2 1EW, England. [Mittal, Jeetain] 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 RI Best, Robert/H-7588-2016 OI Best, Robert/0000-0002-7893-3543 FU Royal Society University Research Fellowship FX We thank Dr. Attila Szabo for constant encouragement and several helpful discussions and Dr. Hoi Sung and Dr. David Minh for pertinent suggestions. This work was supported by the National Institute of Diabetes and Digestive and Kidney Diseases Intramural Research Program. This study used the high-performance computational capabilities of the Biowulf PC/Linux cluster at the National Institutes of Health. J. M. thanks Dr. Artur Adib for supporting a postdoctoral fellowship. R. B. was supported by a Royal Society University Research Fellowship. NR 57 TC 88 Z9 88 U1 4 U2 32 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 23 PY 2008 VL 105 IS 51 BP 20233 EP 20238 DI 10.1073/pnas.0807742105 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 388BP UT WOS:000261995600041 PM 19073911 ER PT J AU Abdelmohsen, K Srikantan, S Kuwano, Y Gorospe, M AF Abdelmohsen, Kotb Srikantan, Subramanya Kuwano, Yuki Gorospe, Myriam TI miR-519 reduces cell proliferation by lowering RNA-binding protein HuR levels SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE elav; microRNA; post-transcriptional gene regulation; ribonucleoprotein complex; translational control ID MESSENGER-RNA; TRANSLATION; PHOSPHORYLATION; EXPRESSION; MICRORNAS; ELEMENT; SENESCENCE; STABILITY; CYTOPLASM; ALPHA AB Gene expression is potently regulated through the action of RNA-binding proteins (RBPs) and microRNAs (miRNAs). Here, we present evidence of a miRNA regulating an RBP. The RBP HuR can stabilize and modulate the translation of numerous target mRNAs involved in cell proliferation, but little is known about the mechanisms that regulate HuR abundance. We identified two putative sites of miR-519 interaction on the HuR mRNA, one in its coding region (CR), one in its 3'-untranslated region (UTR). In several human carcinoma cell lines tested, HeLa (cervical), HCT116 and RKO (colon), and A2780 (ovarian), overexpression of a miR-519 precursor [(Pre) miR-519] reduced HuR abundance, while inhibiting miR-519 by using an antisense RNA [(AS) miR-519] elevated HuR levels. The influence of miR-519 was recapitulated using heterologous reporter constructs that revealed a greater repressive effect on the HuR CR than the HuR 3'-UTR target sequences. miR-519 did not alter HuR mRNA abundance, but reduced HuR biosynthesis, as determined by measuring nascent HuR translation and HuR mRNA association with polysomes. Modulation of miR-519 leading to altered HuR levels in turn affected the levels of proteins encoded by HuR target mRNAs. In keeping with HuR's proliferative influence, (AS) miR-519 significantly increased cell number and [H-3]-thymidine incorporation, while (Pre) miR-519 reduced these parameters. Importantly, the growth-promoting effects of (AS) miR-519 required the presence of HuR, because downregulation of HuR by RNAi dramatically suppressed its proliferative action. In sum, miR-519 represses HuR translation, in turn reducing HuR-regulated gene expression and cell division. C1 [Abdelmohsen, Kotb; Srikantan, Subramanya; Kuwano, Yuki; Gorospe, Myriam] NIA, Cellular & Mol Biol Lab, IRP, NIH, Baltimore, MD 21224 USA. RP Abdelmohsen, K (reprint author), NIA, Cellular & Mol Biol Lab, IRP, NIH, Baltimore, MD 21224 USA. EM abdelmohsenk@grc.nia.nih.gov; myriam-gorospe@nih.gov OI srikantan, subramanya/0000-0003-1810-6519; abdelmohsen, Kotb/0000-0001-6240-5810 FU Intramural Research Program (IRP) of the NIA, National Institutes of Health FX We are grateful to P. J. Morin (National Institute on Aging, NIA) for providing cell lines and to R. Wersto and his team for assistance with flow cytometry. This research was supported entirely by the Intramural Research Program (IRP) of the NIA, National Institutes of Health. NR 33 TC 124 Z9 127 U1 1 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 23 PY 2008 VL 105 IS 51 BP 20297 EP 20302 DI 10.1073/pnas.0809376106 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 388BP UT WOS:000261995600052 PM 19088191 ER PT J AU Hou, CH Zhao, H Tanimoto, K Dean, A AF Hou, Chunhui Zhao, Hui Tanimoto, Keiji Dean, Ann TI CTCF-dependent enhancer-blocking by alternative chromatin loop formation SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE beta-globin genes; insulator; locus control region; epigenetics; transcription regulation ID BETA-GLOBIN LOCUS; TRANSCRIPTION FACTOR GATA-1; CONTROL REGION; GENE-EXPRESSION; ERYTHROID-CELLS; HISTONE MODIFICATION; DOMAIN ACTIVATION; PROTEIN CTCF; HUMAN GENOME; FACTOR EKLF AB The mechanism underlying enhancer-blocking by insulators is unclear. We explored the activity of human beta-globin HS5, the orthologue of the CTCF-dependent chicken HS4 insulator. An extra copy of HS5 placed between the beta-globin locus control region (LCR) and downstream genes on a transgene fulfills the classic predictions for an enhancer-blocker. Ectopic HS5 does not perturb the LCR but blocks gene activation by interfering with RNA pol II, activator and coactivator recruitment, and epigenetic modification at the downstream beta-globin gene. Underlying these effects, ectopic HS5 disrupts chromatin loop formation between beta-globin and the LCR, and instead forms a new loop with endogenous HS5 that topologically isolates the LCR. Both enhancer-blocking and insulator-loop formation depend on an intact CTCF site in ectopic HS5 and are sensitive to knock-down of the CTCF protein by siRNA. Thus, intrinsic looping activity of CTCF sites can nullify LCR function. C1 [Hou, Chunhui; Zhao, Hui; Dean, Ann] NIDDKD, Cellular & Dev Biol Lab, NIH, Bethesda, MD 20892 USA. [Tanimoto, Keiji] Univ Tsukuba, Grad Sch Life & Environm Sci, Tsukuba, Ibaraki 3058577, Japan. RP Dean, A (reprint author), NIDDKD, Cellular & Dev Biol Lab, NIH, Bethesda, MD 20892 USA. EM anndean@helix.nih.gov RI Hou, Chunhui/A-6596-2009; Tanimoto, Keiji/B-2600-2014 FU Intramural Program of the National Institute of Diabetes and Digestive and Kidney Diseases; National Institutes of Health FX We thank Drs. Elissa Lei, Vasily Studitsky, and Rohinton Kamakaka for critical comments on the manuscript. This research was supported by the Intramural Program of the National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health. NR 43 TC 80 Z9 83 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 23 PY 2008 VL 105 IS 51 BP 20398 EP 20403 DI 10.1073/pnas.0808506106 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 388BP UT WOS:000261995600069 PM 19074263 ER PT J AU Heller, NM Qi, XL Junttila, IS Shirey, KA Vogel, SN Paul, WE Keegan, AD AF Heller, Nicola M. Qi, Xiulan Junttila, Ilkka S. Shirey, Kari Ann Vogel, Stefanie N. Paul, William E. Keegan, Achsah D. TI Type I IL-4Rs Selectively Activate IRS-2 to Induce Target Gene Expression in Macrophages SO SCIENCE SIGNALING LA English DT Article AB Although interleukin-4 (IL-4) and IL-13 participate in allergic inflammation and share a receptor subunit (IL-4R alpha), they have different functions. We compared cells expressing type I and II IL-4Rs with cells expressing only type II receptors for their responsiveness to these cytokines. IL-4 induced highly efficient, gamma C-dependent tyrosine phosphorylation of insulin receptor substrate 2 (IRS-2), whereas IL-13 was less effective, even when phosphorylation of signal transducer and activator of transcription 6 (STAT6) was maximal. Only type I receptor, gamma C-dependent signaling induced efficient association of IRS-2 with the p85 subunit of phosphoinositide 3-kinase or the adaptor protein growth factor receptor-bound protein 2. In addition, IL-4 signaling through type I IL-4Rs induced more robust expression of a subset of genes associated with alternatively activated macrophages than did IL-13. Thus, IL-4 activates signaling pathways through type I IL-4Rs qualitatively differently from IL-13, which cooperate to induce optimal gene expression. C1 [Heller, Nicola M.; Qi, Xiulan; Keegan, Achsah D.] Univ Maryland, Sch Med, Ctr Vasc & Inflammatory Dis, Marlene & Stewart Greenebaum Canc Ctr, Baltimore, MD 21201 USA. [Heller, Nicola M.; Qi, Xiulan; Shirey, Kari Ann; Vogel, Stefanie N.; Keegan, Achsah D.] Univ Maryland, Sch Med, Dept Microbiol & Immunol, Baltimore, MD 21201 USA. [Junttila, Ilkka S.; Paul, William E.] NIAID, Immunol Lab, NIH, Bethesda, MD 20892 USA. RP Keegan, AD (reprint author), Univ Maryland, Sch Med, Ctr Vasc & Inflammatory Dis, Marlene & Stewart Greenebaum Canc Ctr, Baltimore, MD 21201 USA. EM akeegan@som.umaryland.edu FU NHLBI NIH HHS [T32 HL 007698, T32 HL007698, T32 HL007698-13, T32 HL007698-14, T32 HL007698-15, T32 HL007698-16]; NIAID NIH HHS [R01 AI038985, AI 018797, AI 038985, AI 059775, R01 AI038985-12A1, R01 AI038985-13, R01 AI038985-14, R01 AI059775, R01 AI059775-01A2, R01 AI059775-02, R01 AI059775-03, R01 AI059775-04, R01 AI059775-05, R37 AI018797, R37 AI018797-25, R37 AI018797-26, R37 AI018797-27] NR 91 TC 62 Z9 62 U1 0 U2 3 PU AMER ASSOC ADVANCEMENT SCIENCE PI WASHINGTON PA 1200 NEW YORK AVE, NW, WASHINGTON, DC 20005 USA SN 1937-9145 J9 SCI SIGNAL JI Sci. Signal. PD DEC 23 PY 2008 VL 1 IS 51 AR ra17 DI 10.1126/scisignal.1164795 PG 14 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA V10XY UT WOS:000207497900004 PM 19109239 ER PT J AU Tai, LH Goulet, ML Belanger, S Toyama-Sorimachi, N Fodil-Cornu, N Vidal, SM Troke, AD McVicar, DW Makrigiannis, AP AF Tai, Lee-Hwa Goulet, Marie-Line Belanger, Simon Toyama-Sorimachi, Noriko Fodil-Cornu, Nassima Vidal, Silvia M. Troke, Angela D. McVicar, Daniel W. Makrigiannis, Andrew P. TI Positive regulation of plasmacytoid dendritic cell function via Ly49Q recognition of class I MHC SO JOURNAL OF EXPERIMENTAL MEDICINE LA English DT Article ID INTERFERON-PRODUCING CELLS; NATURAL-KILLER-CELLS; INHIBITORY NK RECEPTOR; IIFN-PRODUCING CELLS; CYTOMEGALOVIRUS-INFECTION; MOUSE-CYTOMEGALOVIRUS; MONOCLONAL-ANTIBODY; VIRAL-INFECTION; C57BL/6 MICE; CLUSTER AB Plasmacytoid dendritic cells (pDCs) are an important source of type I interferon (IFN) during initial immune responses to viral infections. In mice, pDCs are uniquely characterized by high-level expression of Ly49Q, a C-type lectin-like receptor specific for class I major histocompatibility complex (MHC) molecules. Despite having a cytoplasmic immunoreceptor tyrosine-based inhibitory motif, Ly49Q was found to enhance pDC function in vitro, as pDC cytokine production in response to the Toll-like receptor (TLR) 9 agonist CpG-oligonucleotide (ODN) could be blocked using soluble monoclonal antibody (mAb) to Ly49Q or H-2K(b). Conversely, CpG-ODN-dependent IFN-alpha production by pDCs was greatly augmented upon receptor cross-linking using immobilized anti-Ly49Q mAb or recombinant H-2K(b) ligand. Accordingly, Ly49Q-deficient pDCs displayed a severely reduced capacity to produce cytokines in response to TLR7 and TLR9 stimulation both in vitro and in vivo. Finally, TLR9-dependent antiviral responses were compromised in Ly49Q-null mice infected with mouse cytomegalovirus. Thus, class I MHC recognition by Ly49Q on pDCs is necessary for optimal activation of innate immune responses in vivo. C1 [Tai, Lee-Hwa; Goulet, Marie-Line; Belanger, Simon; Troke, Angela D.; Makrigiannis, Andrew P.] Clin Res Inst Montreal, Lab Mol Immunol, Montreal, PQ H2W 1R7, Canada. [Tai, Lee-Hwa; Goulet, Marie-Line; Belanger, Simon; Vidal, Silvia M.; Troke, Angela D.; Makrigiannis, Andrew P.] McGill Univ, Dept Microbiol & Immunol, Montreal, PQ H3G 1Y6, Canada. [Toyama-Sorimachi, Noriko] Int Med Ctr Japan, Res Inst, Dept Gastroenterol, Shinjuku Ku, Tokyo 1628655, Japan. [Fodil-Cornu, Nassima; Vidal, Silvia M.] McGill Univ, Dept Human Genet, Montreal, PQ H3A 2B4, Canada. [Fodil-Cornu, Nassima; Vidal, Silvia M.] McGill Univ, McGill Ctr Study Host Resistance, Montreal, PQ H3A 2B4, Canada. [McVicar, Daniel W.] NCI, Canc & Inflammat Program, Expt Immunol Lab, Ctr Canc Res, Frederick, MD 21702 USA. RP Makrigiannis, AP (reprint author), Clin Res Inst Montreal, Lab Mol Immunol, 110 Pine Ave W, Montreal, PQ H2W 1R7, Canada. EM makriga@ircm.qc.ca RI McVicar, Daniel/G-1970-2015 FU Canadian Institutes of Health Research (CIHR) [MOP 62841] FX This work was supported by an operating grant ( MOP 62841) from the Canadian Institutes of Health Research (CIHR). L-H. Tai is supported by a CIHR Cancer Training Program scholarship. S. Belanger is supported by a Fonds de la recherche en sante Quebec scholarship. A. P. Makrigiannis is supported by a New Investigator Award from the CIHR. NR 39 TC 38 Z9 38 U1 0 U2 0 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 22 PY 2008 VL 205 IS 13 BP 3187 EP 3199 DI 10.1084/jem.20080718 PG 13 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA 450VH UT WOS:000266428700022 PM 19075287 ER PT J AU Anton, O Batista, A Millan, J Andres-Delgado, L Puertollano, R Correas, I Alonso, MA AF Anton, Olga Batista, Alicia Millan, Jaime Andres-Delgado, Laura Puertollano, Rosa Correas, Isabel Alonso, Miguel A. TI An essential role for the MAL protein in targeting Lck to the plasma membrane of human T lymphocytes SO JOURNAL OF EXPERIMENTAL MEDICINE LA English DT Article ID DARBY CANINE KIDNEY; RAFT-ASSOCIATED PROTEIN; INFLUENZA-VIRUS HEMAGGLUTININ; NORMAL APICAL TRANSPORT; CELL ANTIGEN RECEPTOR; LIPID RAFTS; IMMUNOLOGICAL SYNAPSE; ANCHORED PROTEINS; TYROSINE KINASES; ACTIVATION AB The MAL protein is an essential component of the specialized machinery for apical targeting in epithelial cells. The src family kinase Lck plays a pivotal role in T cell signaling. We show that MAL is required in T cells for efficient expression of Lck at the plasma membrane and activation of IL-2 transcription. To investigate the mechanism by which MAL regulates Lck targeting, we analyzed the dynamics of Lck and found that it travels to the plasma membrane in specific transport carriers containing MAL. Coimmunoprecipitation experiments indicated an association of MAL with Lck. Both carrier formation and partitioning of Lck into detergent-insoluble membranes were ablated in the absence of MAL. Polarization of T cell receptor for antigen (TCR) and microtubule-organizing center to immunological synapse ( IS) were also defective. Although partial correction of the latter defects was possible by forced expression of Lck at the plasma membrane, their complete correction, formation of transport vesicles, partitioning of Lck, and restoration of signaling pathways, which are required for IL-2 transcription up-regulation, were achieved by exogenous expression of MAL. We concluded that MAL is required for recruitment of Lck to specialized membranes and formation of specific transport carriers for Lck targeting. This novel transport pathway is crucial for TCR-mediated signaling and IS assembly. C1 [Anton, Olga; Batista, Alicia; Millan, Jaime; Andres-Delgado, Laura; Correas, Isabel; Alonso, Miguel A.] Univ Autonoma Madrid, CSIC, Ctr Biol Mol Severo Ochoa, E-28049 Madrid, Spain. [Puertollano, Rosa] NHLBI, Cell Biol Lab, NIH, Bethesda, MD 20892 USA. RP Alonso, MA (reprint author), Univ Autonoma Madrid, CSIC, Ctr Biol Mol Severo Ochoa, E-28049 Madrid, Spain. EM maalonso@cbm.uam.es RI Andres-Delgado, Laura/L-8249-2014; Alonso, Miguel/J-3945-2016 OI Andres-Delgado, Laura/0000-0002-8223-4841; Alonso, Miguel/0000-0002-7001-8826 FU Ministerio de Educacion y Ciencia, Spain [BFU2006-01925]; Intramural Research Program of the National Institutes of Health, National Heart, Lung, and Blood Institute (NHLBI); Fundacion Ramon Areces to Centro de Biolog a Molecular FX This work was supported by grants from the Ministerio de Educacion y Ciencia, Spain (BFU2006-01925 to M. A. Alonso) and from the Intramural Research Program of the National Institutes of Health, National Heart, Lung, and Blood Institute (NHLBI; to R. Puertollano). An institutional grant from the Fundacion Ramon Areces to Centro de Biolog a Molecular "Severo Ochoa" is also acknowledged. NR 48 TC 30 Z9 30 U1 0 U2 4 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 22 PY 2008 VL 205 IS 13 BP 3201 EP 3213 DI 10.1084/jem.20080552 PG 13 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA 450VH UT WOS:000266428700023 PM 19064697 ER PT J AU Peppercorn, J Burstein, H Miller, FG Winer, E Joffe, S AF Peppercorn, Jeffrey Burstein, Harold Miller, Franklin G. Winer, Eric Joffe, Steve TI Self-Reported Practices and Attitudes of US Oncologists Regarding Off-Protocol Therapy SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article ID HIGH-DOSE CHEMOTHERAPY; BREAST-CANCER; CLINICAL-TRIALS; AMERICAN ONCOLOGISTS; PARTICIPATION; INTERFERON; DECISION; SOCIETY; DRUGS; VIEWS AB Purpose Investigational cancer therapies being tested in clinical trials may be available outside of trials, or off-protocol (OPRx). We evaluated the practices and attitudes among US oncologists with regard to this controversial practice. Methods We mailed an anonymous survey to a random sample of US medical oncologists evaluating frequency and prevalence of OPRx and evaluated the correlation between demographic factors, attitudes, and practice. Results One hundred forty-six (31%) of 471 oncologists responded. Ninety-three percent reported ever discussing and 81% ever prescribing OPRx. Academic oncologists were more likely than community oncologists to have ever provided OPRx (89% v 75%; P = .06), to discuss OPRx at least once/month (41% v 19%; P = .0004), and to deny requests for OPRx at least once/month (16% v 2%; P = .004). While 61% of oncologists believed that patients should be discouraged from OPRx, only 31% felt it should not be available. With regard to trial recruitment, 53% felt that informed consent requires discussion of OPRx, 34% disagree, and 26% feel that patients should be provided OPRx on request, while 56% disagree. There was lack of consensus on access to OPRx in scenarios based on open trials at the time of the survey, such as adjuvant trastuzumab, which 41% would provide, 59% would not. Conclusion US oncologists report common discussion and use of OPRx, but attitudes and practices may vary substantially. There is need for greater debate regarding OPRx in oncology, further definition of the ethical and clinical issues at stake, and development of guidelines in this area. C1 [Peppercorn, Jeffrey] Duke Univ, Med Ctr, Div Med Oncol, Durham, NC 27710 USA. Duke Univ, Med Ctr, Duke Comprehens Canc Ctr, Durham, NC 27710 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. NIH, Bethesda, MD 20892 USA. RP Peppercorn, J (reprint author), Duke Univ, Med Ctr, Div Med Oncol, Box 3446, Durham, NC 27710 USA. EM jeffrey.peppercorn@duke.edu OI Joffe, Steven/0000-0002-0667-7384 FU American Society of Clinical Oncology Foundation; Breast Cancer Research Foundation; Greenwall Foundation FX Supported by the American Society of Clinical Oncology Foundation (J.P.), Breast Cancer Research Foundation (J.P.), and by the Greenwall Foundation Faculty Scholars Program in Bioethics (J.P.) NR 24 TC 12 Z9 12 U1 0 U2 0 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD DEC 20 PY 2008 VL 26 IS 36 BP 5994 EP 6000 DI 10.1200/JCO.2008.18.1420 PG 7 WC Oncology SC Oncology GA 385WF UT WOS:000261843600026 PM 19029413 ER PT J AU Muse, M Kane, JAC Carr, DJJ Farber, JM Lane, TE AF Muse, Michael Kane, Joy A. C. Carr, Daniel J. J. Farber, Joshua M. Lane, Thomas E. TI Insertion of the CXC chemokine ligand 9 (CXCL9) into the mouse hepatitis virus genome results in protection from viral-induced encephalitis and hepatitis SO VIROLOGY LA English DT Article DE Chemokines; Virus; Central nervous system; Host defense ID CENTRAL-NERVOUS-SYSTEM; INTERFERON-INDUCIBLE CHEMOKINES; TARGETED RNA RECOMBINATION; ACTIVITY IN-VIVO; HOST-DEFENSE; IFN-GAMMA; CORONAVIRUS INFECTION; T-CELLS; NEUROTROPIC CORONAVIRUS; MULTIPLE-SCLEROSIS AB The role of the CXC chemokine ligand 9 (CXCL9) in host defense following infection with mouse hepatitis virus (MHV) was determined. Inoculation of the central nervous system (CNS) of CXCL9-/- mice with MHV resulted in accelerated and increased mortality compared to wild type mice supporting an important role for CXCL9 in anti-viral defense. In addition, infection of RAG1-/- or CXCL9-/- mice with a recombinant MHV expressing CXCL9 (MHV-CXCL9) resulted in protection from disease that correlated with reduced viral titers within the brain and NK cell-mediated protection in the liver. Survival in MHV-CXCL9-infected CXCL9-/- Mice was associated with reduced viral burden within the brain that coincided with increased T cell infiltration. Similarly, viral clearance from the livers of MHV-CXCL9-infected mice was accelerated but independent of increased T cell or INK cell infiltration. These observations indicate that CXCL9 promotes protection from coronavirus-induced neurololgical and liver disease. (C) 2008 Elsevier Inc. All rights reserved. C1 [Muse, Michael; Kane, Joy A. C.; Lane, Thomas E.] Univ Calif Irvine, Dept Mol Biol & Biochem, Irvine, CA 92619 USA. [Carr, Daniel J. J.] Univ Oklahoma, Hlth Sci Ctr, Dept Ophthalmol, Oklahoma City, OK 73104 USA. [Farber, Joshua M.] NIH, Lab Mol Immunol, Inflammat Biol Sect, Bethesda, MD 20892 USA. [Lane, Thomas E.] Univ Calif Irvine, Ctr Immunol, Irvine, CA 92619 USA. RP Lane, TE (reprint author), Univ Calif Irvine, Dept Mol Biol & Biochem, 3205 McGaugh Hall, Irvine, CA 92619 USA. EM tlane@uci.edu FU National Institutes of Health [NS41249, A1067309]; National Multiple Sclerosis Society [3278-A-3] FX This work was supported by National Institutes of Health grants NS41249 (T.E.L.) A1067309 (D.J.J.C.) and National Multiple Sclerosis Society Grant 3278-A-3 to T.E.L. NR 40 TC 11 Z9 11 U1 0 U2 1 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0042-6822 J9 VIROLOGY JI Virology PD DEC 20 PY 2008 VL 382 IS 2 BP 132 EP 144 DI 10.1016/j.virol.2008.09.032 PG 13 WC Virology SC Virology GA 380NM UT WOS:000261472400002 PM 18973912 ER PT J AU Bogers, WMJM Davis, D Baak, I Kan, E Hofman, S Sun, Y Mortier, D Lian, Y Oostermeijer, H Fagrouch, Z Dubbes, R van der Maas, M Mooij, P Koopman, G Verschoor, E Langedijk, JPM Zhao, J Brocca-Cofano, E Robert-Guroff, M Srivastava, I Barnett, S Heeney, JL AF Bogers, Willy M. J. M. Davis, David Baak, Ilona Kan, Elaine Hofman, Sam Sun, Yide Mortier, Daniella Lian, Ying Oostermeijer, Herman Fagrouch, Zahra Dubbes, Rob van der Maas, Martin Mooij, Petra Koopman, Gerrit Verschoor, Ernst Langedijk, Johannes P. M. Zhao, Jun Brocca-Cofano, Egidio Robert-Guroff, Marjorie Srivastava, Indresh Barnett, Susan Heeney, Jonathan L. TI Systemic neutralizing antibodies induced by long interval mucosally primed systemically boosted immunization correlate with protection from mucosal SHIV challenge SO VIROLOGY LA English DT Article DE HIV vaccine; Animal model; Mucosal challenge; Nabs; ADCC ID HUMAN-IMMUNODEFICIENCY-VIRUS; VENEZUELAN EQUINE ENCEPHALITIS; RHESUS MACAQUES; IMMUNE-RESPONSES; VACCINE VECTOR; ENVELOPE IMMUNOGENS; SIVMAC251 CHALLENGE; REPLICON PARTICLES; CELLULAR-IMMUNITY; VAGINAL CHALLENGE AB Immune correlates of vaccine protection from HIV-1 infection would provide important milestones to guide HIV-1 vaccine development. In a proof of concept study using mucosal priming and systemic boosting, the titer of neutralizing antibodies in sera was found to correlate with protection of mucosally exposed rhesus macaques from SHIV infection. Mucosal priming consisted of two sequential immunizations at 12-week intervals with replicating host range mutants of adenovirus type 5 (Ad5hr) expressing the HIV-1(89.6p) env gene. Following boosting with either heterologous recombinant protein or alphavirus replicons at 12-week intervals animals were intrarectally exposed to infections doses of the CCR5 tropic SHIV(SF162p4). Heterologous mucosal prime systemic boost immunization elicited neutralizing antibodies (Nabs), antibody-dependent cytotoxicity (ADCC), and specific patterns of antibody binding to envelope peptides. Vaccine induced protection did not correlate with the type of boost nor-F-cell responses, but rather with the Nab titer prior to exposure. (C) 2008 Elsevier Inc. All rights reserved. C1 [Bogers, Willy M. J. M.; Davis, David; Baak, Ilona; Hofman, Sam; Mortier, Daniella; Oostermeijer, Herman; Fagrouch, Zahra; Dubbes, Rob; van der Maas, Martin; Mooij, Petra; Koopman, Gerrit; Verschoor, Ernst; Heeney, Jonathan L.] BPRC, Dept Virol, NL-2280 GH Rijswijk, Netherlands. [Kan, Elaine; Sun, Yide; Lian, Ying; Srivastava, Indresh; Barnett, Susan] Novartis, Emeryville, CA 94608 USA. [Langedijk, Johannes P. M.] Pepscan therapeut BV, Lelystad, Netherlands. [Zhao, Jun; Brocca-Cofano, Egidio; Robert-Guroff, Marjorie] NCI, Vaccine Branch, Bethesda, MD 20892 USA. [Heeney, Jonathan L.] Univ Cambridge, Cambridge CB3 0ES, England. RP Bogers, WMJM (reprint author), BPRC, Dept Virol, POB 3306, NL-2280 GH Rijswijk, Netherlands. EM bogers@bprc.nl OI Heeney, Jonathan/0000-0003-2702-1621 FU National Institutes of Health, National Cancer Institute; National Institute of Allergy and Infectious Diseases, National Institutes of Health, Department of Health and Human Services [1 P01 A148225-01A2, 5 PO1 A1066287-02] FX This work was supported in part by the Intramural Research Program of the National Institutes of Health, National Cancer Institute, and by Federal funds from the National Institute of Allergy and Infectious Diseases, National Institutes of Health, Department of Health and Human Services, under Contract No. 1 P01 A148225-01A2 and No. 5 PO1 A1066287-02. NR 49 TC 47 Z9 49 U1 0 U2 0 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0042-6822 J9 VIROLOGY JI Virology PD DEC 20 PY 2008 VL 382 IS 2 BP 217 EP 225 DI 10.1016/j.virol.2008.09.016 PG 9 WC Virology SC Virology GA 380NM UT WOS:000261472400010 PM 18947849 ER PT J AU Wang, L Wildt, KF Castro, E Xiong, Y Feigenbaum, L Tessarollo, L Bosselut, R AF Wang, Lie Wildt, Kathryn F. Castro, Ehydel Xiong, Yumei Feigenbaum, Lionel Tessarollo, Lino Bosselut, Remy TI The Zinc Finger Transcription Factor Zbtb7b Represses CD8-Lineage Gene Expression in Peripheral CD4(+) T Cells SO IMMUNITY LA English DT Article ID CD4-CD8 LINEAGE DIFFERENTIATION; IFN-GAMMA PRODUCTION; HELPER TYPE-1 CELLS; IN-VIVO; THYMOCYTE DIFFERENTIATION; LYMPHOCYTE DEVELOPMENT; POSITIVE SELECTION; RUNX PROTEINS; REGULATES CD4; FACTOR GATA-3 AB How CD4-CD8 differentiation is maintained in mature T cells is largely unknown. The present study has examined the role in this process of the zinc finger protein Zbtb7b, a critical factor for the commitment of MHC II-restricted thymocytes to the CD4(+) lineage. We showed that Zbtb7b acted in peripheral CD4(+) T cells to suppress CD8-lineage gene expression, including that of CD8 and cytotoxic effector genes perforin and Granzyme B, and was important for the proper repression of interferon-gamma (IFN-gamma) during effector differentiation. The inappropriate expression of IFN-gamma by Zbtb7b-deficient CD4(+) T cells required the activities of Eomesodermin and Runx transcription factors. Runx activity was needed for Granzyme B expression, indicating that Runx proteins control expression of the cytotoxic program. We conclude that a key function of Zbtb7b in the mature CD4(+) T cell compartment is to repress CD8-lineage gene expression. C1 [Wang, Lie; Wildt, Kathryn F.; Castro, Ehydel; Xiong, Yumei; Bosselut, Remy] NCI, Lab Immune Cell Biol, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. [Feigenbaum, Lionel] NCI SAIC, Frederick, MD 21702 USA. [Tessarollo, Lino] NCI, Mouse Canc Genet Program, CCR, Frederick, MD 21702 USA. RP Bosselut, R (reprint author), NCI, Lab Immune Cell Biol, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. EM remy@helix.nih.gov FU Intramural Research Program of the National Cancer Institute; Center for Cancer Research, NIH FX We thank E. Southon for ES cell recombination; G. Sanchez for mouse technical assistance; B. Taylor and S. Banerjee for expert cell sorting; S. Reiner, B. Paul, and J. Zhu for reagents; S.R. Jenkinson and J. Zhu for helpful discussions and T cell activation protocols; and J. Ashwell, Y. Belkaid, and S. Reiner for reading the manuscript. This work was supported by the Intramural Research Program of the National Cancer Institute, Center for Cancer Research, NIH. NR 54 TC 60 Z9 62 U1 2 U2 7 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 1074-7613 J9 IMMUNITY JI Immunity PD DEC 19 PY 2008 VL 29 IS 6 BP 876 EP 887 DI 10.1016/j.immuni.2008.09.019 PG 12 WC Immunology SC Immunology GA 388IB UT WOS:000262012400008 PM 19062319 ER PT J AU Migueles, SA Osborne, CM Royce, C Compton, AA Joshi, RP Weeks, KA Rood, JE Berkley, AM Sacha, JB Cogliano-Shutta, NA Lloyd, M Roby, G Kwan, R McLaughlin, M Stallings, S Rehm, C O'Shea, MA Mican, J Packard, BZ Komoriya, A Palmer, S Wiegand, AP Maldarelli, F Coffin, JM Mellors, JW Hallahan, CW Follman, DA Connors, M AF Migueles, Stephen A. Osborne, Christine M. Royce, Cassandra Compton, Alex A. Joshi, Rohan P. Weeks, Kristin A. Rood, Julia E. Berkley, Amy M. Sacha, Jonah B. Cogliano-Shutta, Nancy A. Lloyd, Margaret Roby, Gregg Kwan, Richard McLaughlin, Mary Stallings, Sara Rehm, Catherine O'Shea, Marie A. Mican, JoAnn Packard, Beverly Z. Komoriya, Akira Palmer, Sarah Wiegand, Ann P. Maldarelli, Frank Coffin, John M. Mellors, John W. Hallahan, Claire W. Follman, Dean A. Connors, Mark TI Lytic Granule Loading of CD8(+) T Cells Is Required for HIV-Infected Cell Elimination Associated with Immune Control SO IMMUNITY LA English DT Article ID ACTIVE ANTIRETROVIRAL THERAPY; IMMUNODEFICIENCY-VIRUS REPLICATION; LONG-TERM NONPROGRESSORS; VIRAL SUPPRESSION; ELITE SUPPRESSORS; ANTIGEN LOAD; MEMORY; EXPRESSION; INDIVIDUALS; EFFECTOR AB Virus-specific CD8(+) T cells probably mediate control over HIV replication in rare individuals, termed long-term nonprogressors; (LTNPs) or elite controllers. Despite extensive investigation, the mechanisms responsible for this control remain incompletely understood. We observed that HIV-specific CD8(+) T cells of LTNPs persisted at higher frequencies than those of treated progressors with equally low amounts of HIV. Measured on a per-cell basis, HIV-specific CDB+ T cells of LTNPs efficiently eliminated primary autologous HIV-infected CD4(+) T cells. This function required lytic granule loading of effectors and delivery of granzyme B to target cells. Defective cytotoxicity of progressor effectors could be restored after treatment with phorbol ester and calcium ionophore. These results establish an effector function and mechanism that clearly segregate with immunologic control of HIV. They also demonstrate that lytic granule contents of memory cells are a critical determinant of cytotoxicity that must be induced for maximal per-cell killing capacity. C1 [Migueles, Stephen A.; Osborne, Christine M.; Royce, Cassandra; Compton, Alex A.; Joshi, Rohan P.; Weeks, Kristin A.; Rood, Julia E.; Berkley, Amy M.; Cogliano-Shutta, Nancy A.; Lloyd, Margaret; Roby, Gregg; Kwan, Richard; McLaughlin, Mary; Stallings, Sara; Rehm, Catherine; O'Shea, Marie A.; Mican, JoAnn; Hallahan, Claire W.; Follman, Dean A.; Connors, Mark] NIAID, NIH, Bethesda, MD 20892 USA. [Sacha, Jonah B.] Univ Wisconsin, Dept Pathol & Lab Med, Madison, WI 53719 USA. [Packard, Beverly Z.; Komoriya, Akira] Oncolmmunin, Gaithersburg, MD 20877 USA. [Palmer, Sarah; Wiegand, Ann P.; Maldarelli, Frank; Coffin, John M.] NCI, HIV Drug Resistance Program, Frederick, MD 21702 USA. [Mellors, John W.] Univ Pittsburgh, Med Ctr, Div Infect Dis, Pittsburgh, PA 15261 USA. RP Connors, M (reprint author), NIAID, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA. EM mconnors@nih.gov OI Compton, Alex/0000-0002-7508-4953 FU Intramural NIH HHS [Z01 AI000855-09] NR 45 TC 299 Z9 303 U1 1 U2 4 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 1074-7613 J9 IMMUNITY JI Immunity PD DEC 19 PY 2008 VL 29 IS 6 BP 1009 EP 1021 DI 10.1016/j.immuni.2008.10.010 PG 13 WC Immunology SC Immunology GA 388IB UT WOS:000262012400019 PM 19062316 ER PT J AU Zhang, J Gao, ZG Yin, J Quon, MJ Ye, JP AF Zhang, Jin Gao, Zhanguo Yin, Jun Quon, Michael J. Ye, Jianping TI S6K Directly Phosphorylates IRS-1 on Ser-270 to Promote Insulin Resistance in Response to TNF-alpha Signaling through IKK2 SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID SUBSTRATE-1 TYROSINE PHOSPHORYLATION; NECROSIS-FACTOR INHIBITION; MULTIPLE SERINE KINASES; RECEPTOR SUBSTRATE-1; PROTEIN-KINASE; SKELETAL-MUSCLE; KAPPA-B; MAMMALIAN TARGET; 3T3-L1 ADIPOCYTES; FATTY-ACID AB S6K1 (p70S6K) is a serine kinase downstream from Akt in the insulin signaling pathway that is involved in negative feedback regulation of insulin action. S6K1 is also activated by TNF-alpha, a pro- inflammatory cytokine. However, its role remains to be characterized. In the current study, we elucidated a mechanism for S6K1 to mediate TNF-alpha-induced insulin resistance in adipocytes and hepatocytes. S6K1 was phosphorylated at Thr-389 in response to TNF-alpha. This led to phosphorylation of IRS-1 by S6K1 at multiple serine residues including Ser-270, Ser-307, Ser-636, and Ser-1101 in human IRS-1 (Ser-265, Ser-302, Ser-632, and Ser- 1097, in rodent IRS-1). Direct phosphorylation of these sites by S6K1 was observed in an in vitro kinase assay using purified IRS-1 and S6K1. Phosphorylation of all these serines was increased in the adipose tissue of obese mice. RNAi knockdown demonstrated an important role for S6K1 in mediating TNF-alpha-induced IRS-1 inhibition that led to impaired insulin-stimulated glucose uptake in adipocytes. A point mutant of IRS-1 (S270A) impaired association of IRS-1 with S6K1 resulting in diminished phosphorylation of IRS-1 at three other S6K1 phosphorylation sites (Ser- 307, Ser- 636, and Ser- 1101). Expression of a dominant negative S6K1 mutant prevented TNF-induced Ser- 270 phosphorylation and IRS-1 protein degradation. Moreover, in IKK2 (but not IKK1)-null cells, TNF-alpha treatment did not result in Thr-389 phosphorylation of S6K1. We present a new mechanism for TNF-alpha to induce insulin resistance that involves activation of S6K by an IKK2-dependent pathway. S6K directly phosphorylates IRS-1 on multiple serine residues to inhibit insulin signaling. C1 [Zhang, Jin; Gao, Zhanguo; Yin, Jun; Ye, Jianping] Louisiana State Univ Syst, Pennington Biomed Res Ctr, Baton Rouge, LA 70808 USA. [Quon, Michael J.] Natl Ctr Complementary & Alternat Med, Diabet Unit, NIH, Bethesda, MD 20892 USA. RP Ye, JP (reprint author), Louisiana State Univ Syst, Pennington Biomed Res Ctr, Baton Rouge, LA 70808 USA. EM yej@pbrc.edu OI Quon, Michael/0000-0002-9601-9915 FU National Institutes of Health Intramural Research Program (NCCAM) [1P30 DK072476]; NIH Grant [DK68036]; ADA Research Award [7-07-RA-189] FX This work was supported, in whole or in part, by National Institutes of Health Intramural Research Program (NCCAM) ( to M. J. Q.), NIDDK CNRU Grant 1P30 DK072476 ( Genomic Core), and the NIH Grant DK68036 and ADA Research Award 7-07-RA-189 ( to J. Y.). The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked "advertisement" in accordance with 18 U. S. C. Section 1734 solely to indicate this fact. NR 50 TC 114 Z9 126 U1 1 U2 9 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 19 PY 2008 VL 283 IS 51 BP 35375 EP 35382 DI 10.1074/jbc.M806480200 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 383QH UT WOS:000261687900008 PM 18952604 ER PT J AU Chi, YH Haller, K Ward, MD Semmes, OJ Li, Y Jeang, KT AF Chi, Ya-Hui Haller, Kerstin Ward, Michael D. Semmes, O. John Li, Yan Jeang, Kuan-Teh TI Requirements for Protein Phosphorylation and the Kinase Activity of Polo-like Kinase 1 (Plk1) for the Kinetochore Function of Mitotic Arrest Deficiency Protein 1 (Mad1) SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID SPINDLE-ASSEMBLY CHECKPOINT; ANAPHASE-PROMOTING COMPLEX/CYCLOSOME; YEAST SACCHAROMYCES-CEREVISIAE; SMALL-MOLECULE INHIBITOR; BUDDING YEAST; BOX DOMAIN; CELLULAR-TRANSFORMATION; MPS1 KINASE; HUMAN LUNG; IN-VITRO AB Mitotic arrest deficiency protein 1 (Mad1) is associated with microtubule-unattached kinetochores in mitotic cells and is a component of the spindle assembly checkpoint (SAC). Here, we have studied the phosphorylation of Mad1 and mapped using liquid chromatography-tandem mass spectrometry several phosphorylated amino acids in this protein. One phosphorylated residue, Thr(680), was characterized to be important for the kinetochore localization of Mad1 and its SAC function. We also found that in mitotic cells Mad1 co-immunoprecipitated with Plk1. Depletion of cellular Plk1 using small interfering RNAs and inhibition of the kinase activity of Plk1 using a kinase-dead mutant or a small molecule inhibitor attenuated Mad1 phosphorylation and its association with kinetochores. Collectively, these findings indicate mechanistic roles contributed by protein phosphorylation and Plk1 to the SAC activity of Mad1. C1 [Chi, Ya-Hui; Haller, Kerstin; Li, Yan; Jeang, Kuan-Teh] NIAID, Mol Virol Sect, Mol Microbiol Lab, NIH, Bethesda, MD 20892 USA. [Ward, Michael D.; Semmes, O. John] Eastern Virginia Med Sch, Dept Microbiol & Mol Cell Biol, Ctr Biomed Proteom, Norfolk, VA 23501 USA. RP Jeang, KT (reprint author), Bldg 4,Rm 306,9000 Rockville Pike, Bethesda, MD 20892 USA. EM kj7e@nih.gov RI Chi, Ya-Hui/B-1080-2010; Jeang, Kuan-Teh/A-2424-2008 FU National Institutes of Health; NIAID FX Supported through intramural funding from the NIAID, National Institutes of Health. To whom correspondence should be addressed: Bldg. 4, Rm. 306, 9000 Rockville Pike, Bethesda, MD 20892-0460. Tel.: 301-496-6680; Fax: 301-480-3686; E- mail: kj7e@ nih. gov. NR 74 TC 14 Z9 16 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 19 PY 2008 VL 283 IS 51 BP 35834 EP 35844 DI 10.1074/jbc.M804967200 PG 11 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 383QH UT WOS:000261687900058 PM 18922800 ER PT J AU Elias, EV Quiroga, R Gottig, N Nakanishi, H Nash, TE Neiman, A Lujan, HD AF Elias, Eliana V. Quiroga, Rodrigo Gottig, Natalia Nakanishi, Hideki Nash, Theodore E. Neiman, Aaron Lujan, Hugo D. TI Characterization of SNAREs Determines the Absence of a Typical Golgi Apparatus in the Ancient Eukaryote Giardia lamblia SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID CYST WALL PROTEINS; PRIMITIVE EUKARYOTE; ENDOPLASMIC-RETICULUM; STRUCTURE PREDICTION; PERIPHERAL VACUOLES; ENDOMEMBRANE SYSTEM; SECRETORY PATHWAY; SURFACE-PROTEINS; SYNTAXIN GENES; BREFELDIN-A AB Giardia is a eukaryotic protozoal parasite with unusual characteristics, such as the absence of a morphologically evident Golgi apparatus. Although both constitutive and regulated pathways for protein secretion are evident in Giardia, little is known about the mechanisms involved in vesicular docking and fusion. In higher eukaryotes, soluble N-ethylmaleimide-sensitive factor attachment protein receptors (SNAREs) of the vesicle-associated membrane protein and syntaxin families play essential roles in these processes. In this work we identified and characterized genes for 17 SNAREs in Giardia to define the minimal set of subcellular organelles present during growth and encystation, in particular the presence or not of a Golgi apparatus. Expression and localization of all Giardia SNAREs demonstrate their presence in distinct subcellular compartments, which may represent the extent of the endomembrane system in eukaryotes. Remarkably, Giardia SNAREs, homologous to Golgi SNAREs from other organisms, do not allow the detection of a typical Golgi apparatus in either proliferating or differentiating trophozoites. However, some features of the Golgi, such as the packaging and sorting function, seem to be performed by the endoplasmic reticulum and/or the nuclear envelope. Moreover, depletion of individual genes demonstrated that several SNAREs are essential for viability, whereas others are dispensable. Thus, Giardia requires a smaller number of SNAREs compared with other eukaryotes to accomplish all of the vesicle trafficking events that are critical for the growth and differentiation of this important human pathogen. C1 [Elias, Eliana V.; Quiroga, Rodrigo; Gottig, Natalia; Lujan, Hugo D.] Catholic Univ Cordoba, Sch Med, Natl Council Sci & Technol, Biochem & Mol Biol Lab, Cordoba, Argentina. [Nakanishi, Hideki; Neiman, Aaron] SUNY Stony Brook, Dept Biochem & Cell Biol, Stony Brook, NY 11794 USA. [Nash, Theodore E.] NIAID, Parasit Dis Lab, NIH, Bethesda, MD 20892 USA. RP Lujan, HD (reprint author), Univ Catolica Cordoba, Fac Med, Lab Bioquim & Biol Mol, Jacinto Rios 571,CP X5004ASK, Cordoba, Argentina. EM hlujan@ucc.edu.ar OI Quiroga, Rodrigo/0000-0001-5015-0531 FU National Institutes of Health NIAID Intramural Research Program; Agencia Nacional para la Promocion de la Ciencia y la Tecnologia (FONCYT); Consejo Nacional de Investigaciones Cientificas y Tecnicas (CONICET); Howard Hughes Medical Institute (HHMI); Universidad Catolica de Cordoba FX This work was supported, in whole or in part, by the National Institutes of Health NIAID Intramural Research Program. This work was also supported by the Agencia Nacional para la Promocion de la Ciencia y la Tecnologia (FONCYT), the Consejo Nacional de Investigaciones Cientificas y Tecnicas (CONICET), the Howard Hughes Medical Institute (HHMI), and the Universidad Catolica de Cordoba. The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked "advertisement" in accordance with 18 U. S. C. Section 1734 solely to indicate this fact. NR 77 TC 19 Z9 19 U1 1 U2 4 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 19 PY 2008 VL 283 IS 51 BP 35996 EP 36010 DI 10.1074/jbc.M806545200 PG 15 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 383QH UT WOS:000261687900074 PM 18930915 ER PT J AU Simpanya, MF Wistow, G Gao, J David, LL Giblin, FJ Mitton, KP AF Simpanya, Mukoma F. Wistow, Graeme Gao, James David, Larry L. Giblin, Frank J. Mitton, Kenneth P. TI Expressed sequence tag analysis of guinea pig (Cavia porcellus) eye tissues for NEIBank SO MOLECULAR VISION LA English DT Article ID OXYGEN IN-VIVO; HYPERBARIC-OXYGEN; GENE-EXPRESSION; TRABECULAR MESHWORK; LENS CRYSTALLINS; NUCLEAR CATARACT; ZETA-CRYSTALLIN; MACULAR DEGENERATION; CORNEAL EPITHELIUM; LIGHT-SCATTERING AB Purpose: To characterize gene expression patterns in guinea pig ocular tissues and identify orthologs of human genes from NEIBank expressed sequence tags. Methods: RNA was extracted from dissected eye tissues of 2.5-month-old guinea pigs to make three unamplified and unnormalized cDNA libraries in the pCMVSport-6 vector for the lens, retina, and eye minus lens and retina. Over 4,000 clones were sequenced from each library and were analyzed using GRIST for clustering and gene identification. Lens crystallin EST data were validated using two-dimensional electrophoresis (2-DE), matrix assisted laser desorption (MALDI), and electrospray ionization mass spectrometry (ESIMS). Results: Combined data from the three libraries generated a total of 6,694 distinctive gene clusters, with each library having between 1,000 and 3,000 clusters. Approximately 60% of the total gene clusters were novel cDNA sequences and had significant homologies to other mammalian sequences in GenBank. Complete cDNA sequences were obtained for many guinea pig lens proteins, including alpha A/alpha Ainsert-, beta N-, and gamma S-crystallins, lengsin and GRIFIN. The ratio of alpha A- to alpha B-crystallin on 2-DE gels was 8: 1 in the lens nucleus and 6.5: 1 in the cortex. Analysis of ESTs, genome sequence, and proteins (by MALDI), did not reveal any evidence for the presence of gamma D-, gamma E-, and gamma F-crystallin in the guinea pig. Predicted masses of many guinea pig lens crystallins were confirmed by ESIMS analysis. For the retina, orthologs of human phototransduction genes were found, such as Rhodopsin, S-antigen (Sag, Arrestin), and Transducin. The guinea-pig ortholog of NRL, a key rod photoreceptor-specific transcription factor, was also represented in EST data. In the 'rest-of-eye' library, the most abundant transcripts included decorin and keratin 12, representative of the cornea. Conclusions: Genomic analysis of guinea pig eye tissues provides sequence-verified clones for future studies. Guinea pig orthologs of many human eye specific genes were identified. Guinea pig gene structures were similar to their human and rodent gene counterparts. Surprisingly, no orthologs of gamma D-, gamma E-, and gamma F-crystallin were found in EST, proteomic, or the current guinea pig genome data. C1 [Simpanya, Mukoma F.; Giblin, Frank J.; Mitton, Kenneth P.] Oakland Univ, Eye Res Inst, Rochester, MI 48309 USA. [Wistow, Graeme; Gao, James] NEI, Sect Mol Struct & Funct Genom, NIH, Bethesda, MD 20892 USA. [David, Larry L.] Oregon Hlth & Sci Univ, Sch Med, Dept Biochem & Mol Biol, Portland, OR 97201 USA. RP Mitton, KP (reprint author), Oakland Univ, Eye Res Inst, 2200 N Squirrel Rd, Rochester, MI 48309 USA. EM mitton@oakland.edu FU NIH [EY02027, EY014803, EY014626, EY07755, EY10572]; NEI intramural FX This work was supported in part by NIH grants EY02027 (F.J.G.), EY014803 (F.J.G.) EY014626 ( K. P. M.), EY07755 ( L. L. D.) and EY10572 ( L. L. D.). G. W. and J.G. are supported by the NEI intramural program. We thank Victor Leverenz for isolation of guinea pig eye tissues and helping in the preparation of the figures, Megan Stewart for photography, Lucinda Robertson for assistance with 2- DE gels, Phillip Wilmarth for assistance in analysis of MS/ MS data, and Paula Pierce (Excalibur Pathology) for eye tissue staining. Sidney Schechet, Lisa Block, Ed Guzman and Patee Buchoff provided additional technical assistance. NR 80 TC 11 Z9 11 U1 0 U2 4 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 19 PY 2008 VL 14 IS 275-80 BP 2413 EP 2427 PG 15 WC Biochemistry & Molecular Biology; Ophthalmology SC Biochemistry & Molecular Biology; Ophthalmology GA 413WH UT WOS:000263822800004 PM 19104676 ER PT J AU Michelson, AM AF Michelson, Alan M. TI DEVELOPMENTAL BIOLOGY From Genetic Association to Genetic Switch SO SCIENCE LA English DT Editorial Material ID SICKLE-CELL-DISEASE; FETAL-HEMOGLOBIN; COMMON; BCL11A C1 [Michelson, Alan M.] NHLBI, NIH, Bethesda, MD 20892 USA. RP Michelson, AM (reprint author), NHLBI, NIH, 31 Ctr Dr, Bethesda, MD 20892 USA. EM michelsonam@mail.nih.gov NR 11 TC 4 Z9 6 U1 0 U2 1 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 19 PY 2008 VL 322 IS 5909 BP 1803 EP 1804 DI 10.1126/science.1169216 PG 2 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 385FF UT WOS:000261799400043 PM 19095932 ER PT J AU Johnson, C Drgon, T Liu, QR Zhang, PW Walther, D Li, CY Anthony, JC Ding, YL Eaton, WW Uhl, GR AF Johnson, Catherine Drgon, Tomas Liu, Qing-Rong Zhang, Ping-Wu Walther, Donna Li, Chuan-Yun Anthony, James C. Ding, Yulan Eaton, William W. Uhl, George R. TI Genome wide association for substance dependence: convergent results from epidemiologic and research volunteer samples SO BMC MEDICAL GENETICS LA English DT Article ID FAGERSTROM TOLERANCE QUESTIONNAIRE; DIAGNOSTIC-INTERVIEW-SCHEDULE; ADDICTION MOLECULAR-GENETICS; NICOTINE DEPENDENCE; INFORMED CONSENT; POLYSUBSTANCE ABUSERS; VULNERABILITY LOCI; SIZE CALCULATIONS; RESPONSE BIAS; RISK RATIOS AB Background: Dependences on addictive substances are substantially-heritable complex disorders whose molecular genetic bases have been partially elucidated by studies that have largely focused on research volunteers, including those recruited in Baltimore. Maryland. Subjects recruited from the Baltimore site of the Epidemiological Catchment Area (ECA) study provide a potentially-useful comparison group for possible confounding features that might arise from selecting research volunteer samples of substance dependent and control individuals. We now report novel SNP (single nucleotide polymorphism) genome wide association (GWA) results for vulnerability to substance dependence in ECA participants, who were initially ascertained as members of a probability sample from Baltimore, and compare the results to those from ethnically-matched Baltimore research volunteers. Results: We identify substantial overlap between the home address zip codes reported by members of these two samples. We find overlapping clusters of SNPs whose allele frequencies differ with nominal significance between substance dependent vs control individuals in both samples. These overlapping clusters of nominally-positive SNPs identify 172 genes in ways that are never found by chance in Monte Carlo simulation studies. Comparison with data from human expressed sequence tags suggests that these genes are expressed in brain, especially in hippocampus and amygdala, to extents that are greater than chance. Conclusion: The convergent results from these probability sample and research volunteer sample datasets support prior genome wide association results. They fail to support the idea that large portions of the molecular genetic results for vulnerability to substance dependence derive from factors that are limited to research volunteers. C1 [Johnson, Catherine; Drgon, Tomas; Liu, Qing-Rong; Zhang, Ping-Wu; Walther, Donna; Li, Chuan-Yun; Uhl, George R.] NIH IRP NIDA, Mol Neurobiol Branch, Baltimore, MD 21224 USA. [Li, Chuan-Yun] Peking Univ, Coll Life Sci, Ctr Bioinformat, Natl Lab Prot Engn & Plant Genet Engn, Beijing 100871, Peoples R China. [Anthony, James C.] Michigan State Univ, Dept Epidemiol, E Lansing, MI 48824 USA. [Ding, Yulan; Eaton, William W.] Johns Hopkins Bloomberg Sch Publ Hlth, Dept Mental Hlth & Hyg, Baltimore, MD 21221 USA. RP Uhl, GR (reprint author), NIH IRP NIDA, Mol Neurobiol Branch, Suite 3510,333 Cassell Dr Baltimore, Baltimore, MD 21224 USA. EM johnsoncat@intra.nida.nih.gov; tdrgon@intra.nida.nih.gov; qrliu@intra.nida.nih.gov; pwzhang@intra.nida.nih.gov; dwalther@intra.nida.nih.gov; lichua@nida.nih.gov; janthony@msu.edu; yding@jhsph.edu; weaton@jhsph.edu; guhl@intra.nida.nih.gov RI Liu, Qing-Rong/A-3059-2012 OI Liu, Qing-Rong/0000-0001-8477-6452 FU NIH; NIDA; DHSS; National Institute of Mental Health [R01-47447, T32-14592]; Johns Hopkins site [UO1 MH 33870] FX We are grateful for thoughtful advice and discussion from Drs N Ialongo, C Storer and P Zandi. This research was supported financially by the NIH Intramural Research Program, NIDA, DHSS and National Institute of Mental Health grants R01-47447 and T32-14592, and Johns Hopkins Bloomberg School of Public Health IRB H. 33.01.03.26.A2 (WE). We are also grateful to the Epidemiologic Catchment Area Program's principal collaborators (D Regier, B Locke, WE and J Burke) and to Drs M Kramer, E Gruenberg, and S Shapiro from the Johns Hopkins site, supported by UO1 MH 33870. NR 39 TC 28 Z9 30 U1 1 U2 3 PU BIOMED CENTRAL LTD PI LONDON PA CURRENT SCIENCE GROUP, MIDDLESEX HOUSE, 34-42 CLEVELAND ST, LONDON W1T 4LB, ENGLAND SN 1471-2350 J9 BMC MED GENET JI BMC Med. Genet. PD DEC 18 PY 2008 VL 9 AR 113 DI 10.1186/1471-2350-9-113 PG 10 WC Genetics & Heredity SC Genetics & Heredity GA 404BB UT WOS:000263124600001 PM 19094236 ER PT J AU Chen, J Bryngelson, JD Thirumalai, D AF Chen, Jie Bryngelson, J. D. Thirumalai, D. TI Estimations of the Size of Nucleation Regions in Globular Proteins SO JOURNAL OF PHYSICAL CHEMISTRY B LA English DT Article ID FOLDING ENERGY LANDSCAPES; TRANSITION-STATE; CONDENSATION MECHANISM; COLLAPSE MECHANISM; LATTICE MODELS; TIME SCALES; KINETICS; NUCLEUS; SEQUENCES; FUNNELS AB Folding of many single-domain proteins has been described using the nucleation-collapse (NC) mechanism. According to NC, folding (formation of secondary structures and tertiary interactions) and chain collapse occur synchronously upon formation of native-like structures involving a critical number of residues. Using simple nucleation theory together with structure-based thermodynamic data, the average size of the most probable nucleus N(R)* for single-domain proteins, is estimated to be between 15 and 30 residues. We argue that finite-sized fluctuations in this estimate can be large so that nearly half of the residues of a 100 residue protein can be part of the folding nucleus. Inclusion of surface area changes in the folded and unfolded states are important in the determination of N(R)*. C1 [Chen, Jie; Thirumalai, D.] Univ Maryland, Inst Phys Sci & Technol, Biophys Program, College Pk, MD 20742 USA. [Thirumalai, D.] Univ Maryland, Dept Chem & Biochem, College Pk, MD 20742 USA. [Bryngelson, J. D.] NIH, Div Comp Res & Technol, Phys Sci Lab, Bethesda, MD 20892 USA. RP Thirumalai, D (reprint author), Univ Maryland, Inst Phys Sci & Technol, Biophys Program, College Pk, MD 20742 USA. EM thirum@glue.umd.edu FU NSF [CHE 05-14056]; Air Force Office of Scientific Research [FA9550-07-1-0098] FX We thank Peter Wolynes for several constructive suggestions. Most of the analysis was performed while J. D. Bryngelson was part of the scientific staff at NIH. This work was supported by grants from NSF (CHE 05-14056) and the Air Force Office of Scientific Research (FA9550-07-1-0098). NR 38 TC 11 Z9 11 U1 0 U2 6 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 18 PY 2008 VL 112 IS 50 BP 16115 EP 16120 DI 10.1021/jp806161k PG 6 WC Chemistry, Physical SC Chemistry GA 383CY UT WOS:000261652900020 PM 19367923 ER PT J AU Sarin, H Kanevsky, AS Wu, HT Brimacombe, KR Fung, SH Sousa, AA Auh, S Wilson, CM Sharma, K Aronova, MA Leapman, RD Griffiths, GL Hall, MD AF Sarin, Hemant Kanevsky, Ariel S. Wu, Haitao Brimacombe, Kyle R. Fung, Steve H. Sousa, Alioscka A. Auh, Sungyoung Wilson, Colin M. Sharma, Kamal Aronova, Maria A. Leapman, Richard D. Griffiths, Gary L. Hall, Matthew D. TI Effective transvascular delivery of nanoparticles across the blood-brain tumor barrier into malignant glioma cells SO JOURNAL OF TRANSLATIONAL MEDICINE LA English DT Article ID IRON-OXIDE NANOPARTICLES; IMAGING CONTRAST AGENTS; DRUG-DELIVERY; CHEMICAL-PROPERTIES; RECURRENT GLIOMAS; MOLECULAR-SIZE; CHEMOTHERAPY; MODEL; PERMEABILITY; DENDRIMERS AB Background: Effective transvascular delivery of nanoparticle-based chemotherapeutics across the blood-brain tumor barrier of malignant gliomas remains a challenge. This is due to our limited understanding of nanoparticle properties in relation to the physiologic size of pores within the blood-brain tumor barrier. Polyamidoamine dendrimers are particularly small multigenerational nanoparticles with uniform sizes within each generation. Dendrimer sizes increase by only 1 to 2 nm with each successive generation. Using functionalized polyamidoamine dendrimer generations 1 through 8, we investigated how nanoparticle size influences particle accumulation within malignant glioma cells. Methods: Magnetic resonance and fluorescence imaging probes were conjugated to the dendrimer terminal amines. Functionalized dendrimers were administered intravenously to rodents with orthotopically grown malignant gliomas. Transvascular transport and accumulation of the nanoparticles in brain tumor tissue was measured in vivo with dynamic contrast-enhanced magnetic resonance imaging. Localization of the nanoparticles within glioma cells was confirmed ex vivo with fluorescence imaging. Results: We found that the intravenously administered functionalized dendrimers less than approximately 11.7 to 11.9 nm in diameter were able to traverse pores of the blood-brain tumor barrier of RG-2 malignant gliomas, while larger ones could not. Of the permeable functionalized dendrimer generations, those that possessed long blood half-lives could accumulate within glioma cells. Conclusion: The therapeutically relevant upper limit of blood-brain tumor barrier pore size is approximately 11.7 to 11.9 nm. Therefore, effective transvascular drug delivery into malignant glioma cells can be accomplished by using nanoparticles that are smaller than 11.7 to 11.9 nm in diameter and possess long blood half-lives. C1 [Sarin, Hemant; Sousa, Alioscka A.; Aronova, Maria A.; Leapman, Richard D.] Natl Inst Biomed Imaging & Bioengn, Natl Inst Hlth, Bethesda, MD 20892 USA. [Sarin, Hemant; Kanevsky, Ariel S.] Natl Inst Hlth, Ctr Clin, Dept Diagnost Radiol, Bethesda, MD 20892 USA. [Wu, Haitao; Wilson, Colin M.; Griffiths, Gary L.] NHLBI, Imaging Probe Dev Ctr, Natl Inst Hlth, Bethesda, MD 20892 USA. [Brimacombe, Kyle R.; Hall, Matthew D.] NCI, Cell Biol Lab, Natl Inst Hlth, Bethesda, MD 20892 USA. [Fung, Steve H.] Massachusetts Gen Hosp, Dept Neuroradiol, Boston, MA 02114 USA. [Auh, Sungyoung] Natl Inst Neurol Disorders & Stroke, Natl Inst Hlth, Bethesda, MD 20892 USA. [Sharma, Kamal] Natl Canc Inst, Metab Branch, Natl Inst Hlth, Bethesda, MD 20892 USA. [Sharma, Kamal] US FDA, Div Biol Drug Prod, Off Oncol Prod, Ctr Drug Evaluat & Res, Silver Spring, MD 20993 USA. RP Sarin, H (reprint author), Natl Inst Biomed Imaging & Bioengn, Natl Inst Hlth, Bethesda, MD 20892 USA. EM sarinh@mail.nih.gov; kanevskya@mail.nih.gov; wuh3@mail.nih.gov; brimacombek@mail.nih.gov; sfung@partners.org; sousaali@mail.nih.gov; auhs@mail.nih.gov; wilsoncm@mail.nih.gov; kamal.sharma@fda.hhs.gov; aronovaa@mail.nih.gov; leapmanr@mail.nih.gov; griffithsgl@mail.nih.gov; hallma@mail.nih.gov RI Hall, Matthew/B-2132-2010; OI Fung, Steve/0000-0002-1177-682X FU National Institute of Biomedical Imaging Bioengineering (NIBIB); National Cancer Institute (NCI); Radiology and Imaging Sciences Program (CC) FX This study was funded by the National Institute of Biomedical Imaging Bioengineering (NIBIB), National Cancer Institute (NCI), and the Radiology and Imaging Sciences Program (CC). We thank Guofeng Zhang of the Laboratory of Bioengineering and Physical Science (NIBIB) and Yide Mi of the Radiology and Imaging Sciences Program (CC) for technical assistance. We thank Daniel Glen and Rick Reynolds of the Scientific and Statistical Computing Core (National Institute of Mental Health [ NIMH]) for their assistance during our use of the Analysis of Functional NeuroImages (AFNI) software suite for data analyses. NR 71 TC 116 Z9 118 U1 2 U2 38 PU BIOMED CENTRAL LTD PI LONDON PA CURRENT SCIENCE GROUP, MIDDLESEX HOUSE, 34-42 CLEVELAND ST, LONDON W1T 4LB, ENGLAND SN 1479-5876 J9 J TRANSL MED JI J. Transl. Med. PD DEC 18 PY 2008 VL 6 AR 80 DI 10.1186/1479-5876-6-80 PG 15 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 409WS UT WOS:000263537100001 PM 19094226 ER PT J AU Swartz, KJ AF Swartz, Kenton J. TI Sensing voltage across lipid membranes SO NATURE LA English DT Review ID SHAKER K+ CHANNEL; GATED POTASSIUM CHANNELS; FOCUSED ELECTRIC-FIELD; DEPENDENT K+; SODIUM-CHANNELS; GATING-CHARGE; S4 SEGMENT; SENSOR MOVEMENT; PROTON CHANNEL; TRANSMEMBRANE MOVEMENT AB The detection of electrical potentials across lipid bilayers by specialized membrane proteins is required for many fundamental cellular processes such as the generation and propagation of nerve impulses. These membrane proteins possess modular voltage- sensing domains, a notable example being the S1- S4 domains of voltage- activated ion channels. Ground- breaking structural studies on these domains explain how voltage sensors are designed and reveal important interactions with the surrounding lipid membrane. Although further structures are needed to understand the conformational changes that occur during voltage sensing, the available data help to frame several key concepts that are fundamental to the mechanism of voltage sensing. C1 [Swartz, Kenton J.] NINDS, Porter Neurosci Res Ctr, Mol Physiol & Biophys Sect, NIH, Bethesda, MD 20892 USA. RP Swartz, KJ (reprint author), NINDS, Porter Neurosci Res Ctr, Mol Physiol & Biophys Sect, NIH, Bldg 36,Rm 4D04, Bethesda, MD 20892 USA. EM swartzk@ninds.nih.gov FU Intramural Research Program of the NINDS; NIH FX I thank J. Diamond, J. Mindell, S. Silberberg and the members of the Swartz laboratory for discussions. I thank R. MacKinnon for providing coordinates for the paddle- chimera and those for the superimposed structures shown in Fig. 3. This work was supported by the Intramural Research Program of the NINDS, NIH. NR 87 TC 165 Z9 166 U1 5 U2 43 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 18 PY 2008 VL 456 IS 7224 BP 891 EP 897 DI 10.1038/nature07620 PG 7 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 384TY UT WOS:000261768300033 PM 19092925 ER PT J AU Lu, JH Marnell, LL Marjon, KD Mold, C Du Clos, TW Sun, PD AF Lu, Jinghua Marnell, Lorraine L. Marjon, Kristopher D. Mold, Carolyn Du Clos, Terry W. Sun, Peter D. TI Structural recognition and functional activation of Fc gamma R by innate pentraxins SO NATURE LA English DT Article ID C-REACTIVE PROTEIN; AMYLOID-P-COMPONENT; HUMAN MONOCYTES; CRYSTAL-STRUCTURE; RECEPTOR-II; SERUM; CELLS; RIIA; PHAGOCYTOSIS; EXPRESSION AB Pentraxins are a family of ancient innate immune mediators conserved throughout evolution. The classical pentraxins include serum amyloid P component ( SAP) and C- reactive protein, which are two of the acute- phase proteins synthesized in response to infection(1,2). Both recognize microbial pathogens and activate the classical complement pathway through C1q ( refs 3 and 4). More recently, members of the pentraxin family were found to interact with cell- surface Fc gamma receptors (Fc gamma R) and activate leukocyte-mediated phagocytosis(5-8). Here we describe the structural mechanism for pentraxin's binding to Fc gamma R and its functional activation of Fc gamma R- mediated phagocytosis and cytokine secretion. The complex structure between human SAP and Fc gamma RIIa reveals a diagonally bound receptor on each SAP pentamer with both D1 and D2 domains of the receptor contacting the ridge helices from two SAP subunits. The 1: 1 stoichiometry between SAP and Fc gamma RIIa infers the requirement for multivalent pathogen binding for receptor aggregation. Mutational and binding studies show that pentraxins are diverse in their binding specificity for Fc gamma R isoforms but conserved in their recognition structure. The shared binding site for SAP and IgG results in competition for Fc gamma R binding and the inhibition of immune- complex- mediated phagocytosis by soluble pentraxins. These results establish antibody- like functions for pentraxins in the Fc gamma R pathway, suggest an evolutionary overlap between the innate and adaptive immune systems, and have new therapeutic implications for autoimmune diseases. C1 [Lu, Jinghua; Sun, Peter D.] NIAID, Struct Immunol Sect, Immunogenet Lab, NIH, Rockville, MD 20852 USA. [Marnell, Lorraine L.; Marjon, Kristopher D.; Mold, Carolyn; Du Clos, Terry W.] Univ New Mexico, Dept Internal Med, Albuquerque, NM 87131 USA. [Marnell, Lorraine L.; Marjon, Kristopher D.; Mold, Carolyn; Du Clos, Terry W.] Univ New Mexico, Dept Mol Genet & Microbiol, Albuquerque, NM 87131 USA. [Du Clos, Terry W.] Vet Adm Med Ctr, Albuquerque, NM 87108 USA. RP Sun, PD (reprint author), NIAID, Struct Immunol Sect, Immunogenet Lab, NIH, Rockville, MD 20852 USA. EM psun@nih.gov RI lu, jinghua/G-5872-2012 FU US Department of Energy; Basic Energy Sciences; Office of Science [W-31-109-Eng-83]; National Institute of Allergy and Infectious Diseases; National Institutes of Health; Department of Veterans Affairs; [RO1 AI28358] FX We thank D. Klinman, G. Cheng, P. W. Dempsey and S. Bolland for providing the bone marrow from the Myd88 2/2, RIP2 2/2 and wild- type C57BL/6 mice, respectively; M. Pancera and B. Dey for technical support in the isothermal titration calorimetry experiments; V. Deretic and S. Master for assistance with confocal microscopy; and B. Bottazzi for providing PTX-3. The X-ray SER-CAT beamlines (www.ser-cat.org/members.html) at the Advanced Photon Source is supported by the US Department of Energy, Basic Energy Sciences, Office of Science, under contract no. W-31-109-Eng-83. This work was supported by intramural research funding from the National Institute of Allergy and Infectious Diseases, National Institutes of Health, and by RO1 AI28358 and by the Department of Veterans Affairs. NR 41 TC 142 Z9 147 U1 1 U2 11 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 18 PY 2008 VL 456 IS 7224 BP 989 EP U86 DI 10.1038/nature07468 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 384TY UT WOS:000261768300054 PM 19011614 ER PT J AU Nickel, JC Krieger, JN McNaughton-Collins, M Anderson, RU Pontari, M Shoskes, DA Litwin, MS Alexander, RB White, PC Berger, R Nadler, R O'Leary, M Liong, ML Zeitlin, S Chuai, S Landis, JR Kusek, JW Nyberg, LM Schaeffer, AJ AF Nickel, J. Curtis Krieger, John N. McNaughton-Collins, Mary Anderson, Rodney U. Pontari, Michel Shoskes, Daniel A. Litwin, Mark S. Alexander, Richard B. White, Paige C. Berger, Richard Nadler, Robert O'Leary, Michael Liong, Men Long Zeitlin, Scott Chuai, Shannon Landis, J. Richard Kusek, John W. Nyberg, Leroy M. Schaeffer, Anthony J. CA Chronic Prostatitis Collaborative TI Alfuzosin and Symptoms of Chronic Prostatitis-Chronic Pelvic Pain Syndrome SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Article ID CHRONIC NONBACTERIAL PROSTATITIS; DOUBLE-BLIND TRIAL; QUALITY-OF-LIFE; ALPHA-BLOCKERS; MEN; MULTICENTER; THERAPY; SCALE; INDEX; QUESTIONNAIRE AB Background: In men with chronic prostatitis-chronic pelvic pain syndrome, treatment with alpha-adrenergic receptor blockers early in the course of the disorder has been reported to be effective in some, but not all, relatively small randomized trials. Methods: We conducted a multicenter, randomized, double-blind, placebo-controlled trial to evaluate the efficacy of alfuzosin, an alpha-adrenergic receptor blocker, in reducing symptoms in men with chronic prostatitis-chronic pelvic pain syndrome. Participation in the study required diagnosis of the condition within the preceding 2 years and no previous treatment with an alpha-adrenergic receptor blocker. Men were randomly assigned to treatment for 12 weeks with either 10 mg of alfuzosin per day or placebo. The primary outcome was a reduction of at least 4 points (from baseline to 12 weeks) in the score on the National Institutes of Health Chronic Prostatitis Symptom Index (NIH-CPSI) (range, 0 to 43; higher scores indicate more severe symptoms). A 4-point decrease is the minimal clinically significant difference in the score. Results: A total of 272 eligible participants underwent randomization, and in both study groups, 49.3% of participants had a decrease of at least 4 points in their total NIH-CPSI score (rate difference associated with alfuzosin, 0.1%; 95% confidence interval, -11.2 to 11.0; P=0.99). In addition, a global response assessment showed similar response rates at 12 weeks: 33.6% in the placebo group and 34.8% in the alfuzosin group (P=0.90). The rates of adverse events in the two groups were also similar. Conclusions: Our findings do not support the use of alfuzosin to reduce the symptoms of chronic prostatitis-chronic pelvic pain syndrome in men who have not received prior treatment with an alpha-blocker. (ClinicalTrials.gov number, NCT00103402.). C1 [Nickel, J. Curtis] Queens Univ, Kingston Gen Hosp, Dept Urol, Kingston, ON K7L 2V7, Canada. [Nickel, J. Curtis] Queens Univ, Dept Urol, Kingston, ON, Canada. [Krieger, John N.; Berger, Richard] Univ Washington, Dept Urol, Seattle, WA USA. [McNaughton-Collins, Mary] Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. [Anderson, Rodney U.] Stanford Univ, Med Ctr, Dept Urol, Stanford, CA 94305 USA. [Pontari, Michel] Temple Univ, Dept Urol, Philadelphia, PA 19122 USA. [Shoskes, Daniel A.] Cleveland Clin, Glickman Urol Inst, Cleveland, OH 44106 USA. [Litwin, Mark S.; Chuai, Shannon] Univ Calif Los Angeles, David Geffen Sch Med, Dept Urol, Los Angeles, CA 90095 USA. [Litwin, Mark S.; Chuai, Shannon] Univ Calif Los Angeles, David Geffen Sch Med, Dept Hlth Serv, Los Angeles, CA 90095 USA. [Litwin, Mark S.; Chuai, Shannon] Univ Calif Los Angeles, Sch Publ Hlth, Los Angeles, CA 90095 USA. [Alexander, Richard B.] Univ Maryland, Dept Urol, Baltimore, MD 21201 USA. [White, Paige C.] Univ Mississippi, Dept Surg, Jackson, MS 39216 USA. [Nadler, Robert; Schaeffer, Anthony J.] Northwestern Univ, Dept Urol, Chicago, IL 60611 USA. [O'Leary, Michael] Brigham & Womens Hosp, Dept Surg, Boston, MA 02115 USA. [Liong, Men Long] Univ Sci Malaysia, George Town, Malaysia. [Zeitlin, Scott; Landis, J. Richard] Univ Penn, Sch Med, Ctr Clin Epidemiol & Biostat, Philadelphia, PA 19104 USA. [Kusek, John W.; Nyberg, Leroy M.] NIDDKD, Bethesda, MD 20892 USA. RP Nickel, JC (reprint author), Queens Univ, Kingston Gen Hosp, Dept Urol, Kingston, ON K7L 2V7, Canada. EM jcn@queensu.ca RI Landis, J. Richard/A-9330-2010 FU NIDDK NIH HHS [U01 DK065209-04S1, U01 DK065174, U01 DK065174-05, U01 DK065186, U01 DK065186-05, U01 DK065187, U01 DK065187-05, U01 DK065189, U01 DK065189-06, U01 DK065209, U01 DK065209-01, U01 DK065209-02, U01 DK065209-02S1, U01 DK065209-03, U01 DK065209-03S1, U01 DK065209-03S2, U01 DK065209-04, U01 DK065209-04S2, U01 DK065209-05, U01 DK065209-05S1, U01 DK065209-06, U01 DK065257, U01 DK065257-05, U01 DK065266, U01 DK065266-05, U01 DK065268, U01 DK065268-05, U01 DK065277, U01 DK065277-05, U01 DK065287, U01 DK065287-03, U01 DK065297, U01 DK065297-05, U01 DK65174, U01 DK65186, U01 DK65187, U01 DK65189, U01 DK65209, U01 DK65257, U01 DK65266, U01 DK65268, U01 DK65277, U01 DK65287, U01 DK65297] NR 36 TC 67 Z9 76 U1 0 U2 2 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 18 PY 2008 VL 359 IS 25 BP 2663 EP 2673 DI 10.1056/NEJMoa0803240 PG 11 WC Medicine, General & Internal SC General & Internal Medicine GA 384PS UT WOS:000261757300006 PM 19092152 ER PT J AU Dotson, CD Zhang, L Xu, H Shin, YK Vigues, S Ott, SH Elson, AET Choi, HJ Shaw, H Egan, JM Mitchell, BD Li, XD Steinle, NI Munger, SD AF Dotson, Cedrick D. Zhang, Lan Xu, Hong Shin, Yu-Kyong Vigues, Stephan Ott, Sandra H. Elson, Amanda E. T. Choi, Hyun Jin Shaw, Hillary Egan, Josephine M. Mitchell, Braxton D. Li, Xiaodong Steinle, Nanette I. Munger, Steven D. TI Bitter Taste Receptors Influence Glucose Homeostasis SO PLOS ONE LA English DT Article AB TAS1R- and TAS2R-type taste receptors are expressed in the gustatory system, where they detect sweet- and bitter-tasting stimuli, respectively. These receptors are also expressed in subsets of cells within the mammalian gastrointestinal tract, where they mediate nutrient assimilation and endocrine responses. For example, sweeteners stimulate taste receptors on the surface of gut enteroendocrine L cells to elicit an increase in intracellular Ca(2+) and secretion of the incretin hormone glucagon-like peptide-1 (GLP-1), an important modulator of insulin biosynthesis and secretion. Because of the importance of taste receptors in the regulation of food intake and the alimentary responses to chemostimuli, we hypothesized that differences in taste receptor efficacy may impact glucose homeostasis. To address this issue, we initiated a candidate gene study within the Amish Family Diabetes Study and assessed the association of taste receptor variants with indicators of glucose dysregulation, including a diagnosis of type 2 diabetes mellitus and high levels of blood glucose and insulin during an oral glucose tolerance test. We report that a TAS2R haplotype is associated with altered glucose and insulin homeostasis. We also found that one SNP within this haplotype disrupts normal responses of a single receptor, TAS2R9, to its cognate ligands ofloxacin, procainamide and pirenzapine. Together, these findings suggest that a functionally compromised TAS2R receptor negatively impacts glucose homeostasis, providing an important link between alimentary chemosensation and metabolic disease. C1 [Dotson, Cedrick D.; Vigues, Stephan; Elson, Amanda E. T.; Choi, Hyun Jin; Munger, Steven D.] Univ Maryland, Sch Med, Dept Anat & Neurobiol, Baltimore, MD 21201 USA. [Zhang, Lan; Xu, Hong; Li, Xiaodong] Senomyx Inc, San Diego, CA USA. [Shin, Yu-Kyong; Egan, Josephine M.] NIA, NIH, Baltimore, MD USA. [Ott, Sandra H.; Shaw, Hillary; Mitchell, Braxton D.; Steinle, Nanette I.] Univ Maryland, Sch Med, Dept Med, Div Endocrinol, Baltimore, MD USA. RP Dotson, CD (reprint author), Univ Maryland, Sch Med, Dept Anat & Neurobiol, Baltimore, MD 21201 USA. EM smung001@umaryland.edu OI Elson, Amanda/0000-0002-5744-5954; Mitchell, Braxton/0000-0003-4920-4744 FU NIDCD [DC005786, DC007317]; NHLBI [HL076768]; University of Maryland School of Medicine, the Clinical Nutrition Research Unit of Maryland [DK072488]; Intramural Research Program of the NIH/National Institute on Aging; NIDCR FX This work was supported by grants from the NIDCD (DC005786 to S.D.M.; DC007317 to S.V.), NHLBI (HL076768 to N.I.S.), the University of Maryland School of Medicine, the Clinical Nutrition Research Unit of Maryland (DK072488), and the Intramural Research Program of the NIH/National Institute on Aging (Y.-K.S. and J.M.E.). C.D.D. was supported by NIDCD and NIDCR training grants. L.Z., H.X. and X.L. are employees of Senomyx, Inc. The funders had no role in decision to publish or preparation of the manuscript. With the exception of studies performed at, and funded by, Senomyx, Inc., the funders had no role in the study design, data collection or analysis. For experiments performed at and funded by Senomyx, Inc. (these are restricted to the receptor deorphaning experiments reported in Figure 2), study design, data collection and analysis was performed according to good scientific practices. Analysis and interpretation of these (Figure 2) experiments were also performed by authors CDD and SDM (University of Maryland School of Medicine). NR 63 TC 86 Z9 89 U1 3 U2 27 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 18 PY 2008 VL 3 IS 12 AR e3974 DI 10.1371/journal.pone.0003974 PG 10 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 437AT UT WOS:000265458600009 PM 19092995 ER PT J AU Luke, BT Collins, JR AF Luke, Brian T. Collins, Jack R. TI Examining the significance of fingerprint-based classifiers SO BMC BIOINFORMATICS LA English DT Article ID SELDI-TOF-MS; SERUM BIOMARKERS; PROSTATE-CANCER; PROTEOMIC ANALYSIS; PANCREATIC-CANCER; BREAST-CANCER; PATTERN; IDENTIFICATION; DIAGNOSIS; DISCOVERY AB Background: Experimental examinations of biofluids to measure concentrations of proteins or their fragments or metabolites are being explored as a means of early disease detection, distinguishing diseases with similar symptoms, and drug treatment efficacy. Many studies have produced classifiers with a high sensitivity and specificity, and it has been argued that accurate results necessarily imply some underlying biology-based features in the classifier. The simplest test of this conjecture is to examine datasets designed to contain no information with classifiers used in many published studies. Results: The classification accuracy of two fingerprint-based classifiers, a decision tree (DT) algorithm and a medoid classification algorithm (MCA), are examined. These methods are used to examine 30 artificial datasets that contain random concentration levels for 300 biomolecules. Each dataset contains between 30 and 300 Cases and Controls, and since the 300 observed concentrations are randomly generated, these datasets are constructed to contain no biological information. A modest search of decision trees containing at most seven decision nodes finds a large number of unique decision trees with an average sensitivity and specificity above 85% for datasets containing 60 Cases and 60 Controls or less, and for datasets with 90 Cases and 90 Controls many DTs have an average sensitivity and specificity above 80%. For even the largest dataset (300 Cases and 300 Controls) the MCA procedure finds several unique classifiers that have an average sensitivity and specificity above 88% using only six or seven features. Conclusion: While it has been argued that accurate classification results must imply some biological basis for the separation of Cases from Controls, our results show that this is not necessarily true. The DT and MCA classifiers are sufficiently flexible and can produce good results from datasets that are specifically constructed to contain no information. This means that a chance fitting to the data is possible. All datasets used in this investigation are available on the web. C1 [Luke, Brian T.; Collins, Jack R.] NCI, SAIC Frederick Inc, Adv Technol Program, Adv Biomed Comp Ctr, Frederick, MD 21702 USA. RP Luke, BT (reprint author), NCI, SAIC Frederick Inc, Adv Technol Program, Adv Biomed Comp Ctr, Frederick, MD 21702 USA. EM lukeb@ncifcrf.gov; collinsj@ncifcrf.gov FU National Cancer Institute; National Institutes of Health [NO1-CO-12400] FX The authors would like to thank the reviewers for their helpful questions and comments. This project has been funded in whole or in part with federal funds from the National Cancer Institute, National Institutes of Health, under Contract NO1-CO-12400. 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 United States Government. NR 38 TC 2 Z9 2 U1 0 U2 2 PU BIOMED CENTRAL LTD PI LONDON PA CURRENT SCIENCE GROUP, MIDDLESEX HOUSE, 34-42 CLEVELAND ST, LONDON W1T 4LB, ENGLAND SN 1471-2105 J9 BMC BIOINFORMATICS JI BMC Bioinformatics PD DEC 17 PY 2008 VL 9 AR 545 DI 10.1186/1471-2105-9-545 PG 9 WC Biochemical Research Methods; Biotechnology & Applied Microbiology; Mathematical & Computational Biology SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Mathematical & Computational Biology GA 402FL UT WOS:000262999500002 PM 19091087 ER PT J AU Kostera-Pruszczyk, A Pruszczyk, P Kaminska, A Lee, HS Goldfarb, LG AF Kostera-Pruszczyk, Anna Pruszczyk, Piotr Kaminska, Anna Lee, Hee-Suk Goldfarb, Lev G. TI Diversity of cardiomyopathy phenotypes caused by mutations in desmin SO INTERNATIONAL JOURNAL OF CARDIOLOGY LA English DT Letter ID RESTRICTIVE CARDIOMYOPATHY; DILATED CARDIOMYOPATHY; MYOPATHY C1 [Pruszczyk, Piotr] Med Univ Warsaw, Dept Internal Med & Cardiol, Warsaw, Poland. [Kostera-Pruszczyk, Anna; Kaminska, Anna] Med Univ Warsaw, Dept Neurol, Warsaw, Poland. [Kaminska, Anna] Polish Acad Sci, Med Res Ctr, Neuromuscular Unit, Warsaw, Poland. [Lee, Hee-Suk; Goldfarb, Lev G.] NINDS, NIH, Bethesda, MD 20892 USA. RP Pruszczyk, P (reprint author), Med Univ Warsaw, Dept Internal Med & Cardiol, Warsaw, Poland. EM pprusz@amwaw.edu.pl NR 11 TC 9 Z9 12 U1 0 U2 0 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0167-5273 J9 INT J CARDIOL JI Int. J. Cardiol. PD DEC 17 PY 2008 VL 131 IS 1 BP 146 EP 147 DI 10.1016/j.ijcard.2007.08.095 PG 2 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 377KX UT WOS:000261251200030 ER PT J AU Rudebeck, PH Behrens, TE Kennerley, SW Baxter, MG Buckley, MJ Walton, ME Rushworth, MFS AF Rudebeck, Peter H. Behrens, Timothy E. Kennerley, Steven W. Baxter, Mark G. Buckley, Mark J. Walton, Mark E. Rushworth, Matthew F. S. TI Frontal Cortex Subregions Play Distinct Roles in Choices between Actions and Stimuli SO JOURNAL OF NEUROSCIENCE LA English DT Article DE reward; prefrontal cortex; learning; macaque; decision; cingulate ID ANTERIOR CINGULATE CORTEX; ORBITAL PREFRONTAL CORTEX; ORBITOFRONTAL CORTEX; DECISION-MAKING; MACAQUE MONKEYS; RHESUS-MONKEYS; REWARD PREFERENCE; MOTOR CORTEX; SELECTION; AMYGDALA AB The orbitofrontal cortex (OFC) has been implicated in reinforcement-guided decision making, error monitoring, and the reversal of behavior in response to changing circumstances. The anterior cingulate cortex sulcus (ACC(S)), however, has also been implicated in similar aspects of behavior. Dissociating the unique functions of these areas would improve our understanding of the decision-making process. The effect of selective OFC lesions on how monkeys used the history of reinforcement to guide choices of either particular actions or particular stimuli was studied and compared with the effects of ACC(S) lesions. Both lesions disrupted decision making, but their effects were differentially modulated by the dependence on action-or stimulus-value contingencies. OFClesions caused a deficit in stimulus but not action selection, whereas ACC(S) lesions had the opposite effect, disrupting action but not stimulus selection. Furthermore, OFClesions that have previously been found to impair decision making when deterministic stimulus-reward contingencies are switched were found to cause a more general learning impairment in more naturalistic situations in which reward was stochastic. Both OFC and ACC(S) are essential for reinforcement-guided decision making rather than just error monitoring or behavioral reversal. The OFC and ACC(S) are both, however, more concerned with learning and making decisions, but their roles in selecting between stimulus and action values are distinct. C1 [Rudebeck, Peter H.; Behrens, Timothy E.; Baxter, Mark G.; Buckley, Mark J.; Walton, Mark E.; Rushworth, Matthew F. S.] Univ Oxford, Dept Expt Psychol, Oxford OX1 3UD, England. [Kennerley, Steven W.] Univ Calif Berkeley, Helen Wills Neurosci Inst, Berkeley, CA 94720 USA. RP Rudebeck, PH (reprint author), NIMH, Neuropsychol Lab, NIH, Bldg 49,Suite 1B80,49 Convent Dr, Bethesda, MD 20892 USA. EM rudebeckp@mail.nih.gov RI Rudebeck, Peter/G-7931-2012; OI Rudebeck, Peter/0000-0002-1411-7555 FU Medical Research Council United Kingdom; The Wellcome Trust FX This work was supported by the Medical Research Council United Kingdom (P.H.R., T.E.B., M.J.B., M.F.S.R.) and The Wellcome Trust (M.E.W., M.G.B.). We thank Dr. D. Gaffan for his advice and encouragement as well as Greg Daubeny for assistance with histology. NR 45 TC 154 Z9 154 U1 0 U2 12 PU SOC NEUROSCIENCE PI WASHINGTON PA 11 DUPONT CIRCLE, NW, STE 500, WASHINGTON, DC 20036 USA SN 0270-6474 J9 J NEUROSCI JI J. Neurosci. PD DEC 17 PY 2008 VL 28 IS 51 BP 13775 EP 13785 DI 10.1523/JNEUROSCI.3541-08.2008 PG 11 WC Neurosciences SC Neurosciences & Neurology GA 384YM UT WOS:000261780100008 PM 19091968 ER PT J AU Lathia, JD Okun, E Tang, SC Griffioen, K Cheng, AW Mughal, MR Laryea, G Selvaraj, PK Ffrench-Constant, C Magnus, T Arumugam, TV Mattson, MP AF Lathia, Justin D. Okun, Eitan Tang, Sung-Chun Griffioen, Kathleen Cheng, Aiwu Mughal, Mohamed R. Laryea, Gloria Selvaraj, Pradeep K. Ffrench-Constant, Charles Magnus, Tim Arumugam, Thiruma V. Mattson, Mark P. TI Toll-Like Receptor 3 Is a Negative Regulator of Embryonic Neural Progenitor Cell Proliferation SO JOURNAL OF NEUROSCIENCE LA English DT Article DE stem cells; embryo; immunity; cortex; neurogenesis; ventricle ID CENTRAL-NERVOUS-SYSTEM; DOUBLE-STRANDED-RNA; DENDRITIC CELLS; BRAIN-INJURY; ACTIVATION; NEUROGENESIS; PATHWAYS; LIGANDS; INNATE; CNS AB Toll-like receptors (TLRs) play important roles in innate immunity. Several TLR family members have recently been shown to be expressed by neurons and glial cells in the adult brain, and may mediate responses of these cells to injury and infection. To address the possibility that TLRs play a functional role in development of the nervous system, we analyzed the expression of TLRs during different stages of mouse brain development and assessed the role of TLRs in cell proliferation. TLR3 protein is present in brain cells in early embryonic stages of development, and in cultured neural stem/progenitor cells (NPC). NPC from TLR3-deficient embryos formed greater numbers of neurospheres compared with neurospheres from wild-type embryos. Numbers of proliferating cells, as assessed by phospho histone H3 and proliferating cell nuclear antigen labeling, were also increased in the developing cortex of TLR3-deficient mice compared with wild-type mice in vivo. Treatment of cultured embryonic cortical neurospheres with a TLR3 ligand (polyIC) significantly reduced proliferating (BrdU-labeled) cells and neurosphere formation in wild type but not TLR3(-/-)-derived NPCs. Our findings reveal a novel role for TLR3 in the negative regulation of NPC proliferation in the developing brain. C1 [Lathia, Justin D.; Okun, Eitan; Tang, Sung-Chun; Griffioen, Kathleen; Cheng, Aiwu; Mughal, Mohamed R.; Laryea, Gloria; Magnus, Tim; Arumugam, Thiruma V.; Mattson, Mark P.] NIA, Neurosci Lab, Intramural Res Program, Baltimore, MD 21224 USA. [Lathia, Justin D.; Ffrench-Constant, Charles] Univ Cambridge, Dept Pathol, Cambridge CB2 1QP, England. [Lathia, Justin D.; Ffrench-Constant, Charles] Univ Cambridge, Ctr Brain Repair, Cambridge CB2 1QP, England. [Tang, Sung-Chun] Natl Taiwan Univ Hosp, Dept Neurol, Yun Lin Branch, Yunlin 640, Taiwan. [Selvaraj, Pradeep K.; Arumugam, Thiruma V.] Texas Tech Univ, Hlth Sci Ctr, Dept Pharmaceut Sci, Amarillo, TX 79106 USA. [Ffrench-Constant, Charles] Univ Edinburgh, Queens Med Res Inst, Multiple Sclerosis Soc Translat Res Ctr, Edinburgh EH16 4TJ, Midlothian, Scotland. [Ffrench-Constant, Charles] MRC, Ctr Regenerat Med, Edinburgh EH16 4TJ, Midlothian, Scotland. [Magnus, Tim] Univ Hamburg, Neurol Univ Klin, D-20246 Hamburg, Germany. [Mattson, Mark P.] Johns Hopkins Univ, Sch Med, Dept Neurosci, Baltimore, MD 21205 USA. RP Mattson, MP (reprint author), NIA, Neurosci Lab, Intramural Res Program, 5600 Nathan Shock Dr, Baltimore, MD 21224 USA. EM mattsonm@grc.nia.nih.gov RI Arumugam, Thiruma/C-7969-2009; Arumugam, Thiruma/B-4898-2011; Mattson, Mark/F-6038-2012; Messier, Claude/A-2322-2008; OI Messier, Claude/0000-0002-4791-1763; Tang, Sung-Chun/0000-0003-3731-5973 FU National Institute on Aging; National Institutes of Health; Wellcome Trust FX This work was supported by the National Institute on Aging Intramural Research Program. J. D. L. is supported by the National Institutes of Health-Cambridge Graduate Partnership Program. C.ff.-C. is supported by the Wellcome Trust. NR 24 TC 81 Z9 82 U1 3 U2 8 PU SOC NEUROSCIENCE PI WASHINGTON PA 11 DUPONT CIRCLE, NW, STE 500, WASHINGTON, DC 20036 USA SN 0270-6474 J9 J NEUROSCI JI J. Neurosci. PD DEC 17 PY 2008 VL 28 IS 51 BP 13978 EP 13984 DI 10.1523/JNEUROSCI.2140-08.2008 PG 7 WC Neurosciences SC Neurosciences & Neurology GA 384YM UT WOS:000261780100026 PM 19091986 ER PT J AU Melis, M Pillolla, G Luchicchi, A Muntoni, AL Yasar, S Goldberg, SR Pistis, M AF Melis, Miriam Pillolla, Giuliano Luchicchi, Antonio Muntoni, Anna Lisa Yasar, Sevil Goldberg, Steven R. Pistis, Marco TI Endogenous Fatty Acid Ethanolamides Suppress Nicotine-Induced Activation of Mesolimbic Dopamine Neurons through Nuclear Receptors SO JOURNAL OF NEUROSCIENCE LA English DT Article DE dopamine neurons; nicotine; electrophysiology; endocannabinoids; fatty acid amide hydrolase; patch clamp; peroxisome proliferator-activated receptor ID VENTRAL TEGMENTAL AREA; MOUSE THALAMIC SYNAPTOSOMES; AMIDE HYDROLASE; ACETYLCHOLINE-RECEPTORS; ANANDAMIDE HYDROLYSIS; PPAR-ALPHA; INFLAMMATORY PAIN; CORTICAL-NEURONS; CB1 RECEPTORS; ESTER URB597 AB Nicotine stimulates the activity of mesolimbic dopamine neurons, which is believed to mediate the rewarding and addictive properties of tobacco use. Accumulating evidence suggests that the endocannabinoid system might play a major role in neuronal mechanisms underlying the rewarding properties of drugs of abuse, including nicotine. Here, we investigated the modulation of nicotine effects by the endocannabinoid system on dopamine neurons in the ventral tegmental area with electrophysiological techniques in vivo and in vitro. We discovered that pharmacological inhibition of fatty acid amide hydrolase (FAAH), the enzyme that catabolizes fatty acid ethanolamides, among which the endocannabinoid anandamide (AEA) is the best known, suppressed nicotine-induced excitation of dopamine cells. Importantly, this effect was mimicked by the administration of the FAAH substrates oleoylethanolamide (OEA) and palmitoylethanolamide (PEA), but not methanandamide, the hydrolysis resistant analog of AEA. OEA and PEA are naturally occurring lipid signaling molecules structurally related to AEA, but devoid of affinity for cannabinoid receptors. They blocked the effects of nicotine by activation of the peroxisome proliferator-activated receptor-alpha (PPAR-alpha), a nuclear receptor transcription factor involved in several aspects of lipid metabolism and energy balance. Activation of PPAR-alpha triggered a nongenomic stimulation of tyrosine kinases, which might lead to phosphorylation and negative regulation of neuronal nicotinic acetylcholine receptors. These data indicate for the first time that the anorexic lipids OEA and PEA possess neuromodulatory properties as endogenous ligands of PPAR-alpha in the brain and provide a potential new target for the treatment of nicotine addiction. C1 [Melis, Miriam; Pillolla, Giuliano; Luchicchi, Antonio; Pistis, Marco] Univ Cagliari, Bb Brodie Dept Neurosci, I-09042 Monserrato, Italy. [Muntoni, Anna Lisa] Univ Cagliari, CNR, Inst Neurosci, I-09042 Monserrato, Italy. [Yasar, Sevil] Johns Hopkins Univ, Sch Med, Dept Med, Div Geriatr Med & Gerontol, Baltimore, MD 21224 USA. [Goldberg, Steven R.] NIDA, Preclin Pharmacol Sect, Behav Neurosci Res Branch,NIH, Intramural Res Program,Dept Hlth & Human Serv, Baltimore, MD 21224 USA. RP Pistis, M (reprint author), Univ Cagliari, Bb Brodie Dept Neurosci, I-09042 Monserrato, Italy. EM mpistis@unica.it RI Pistis, Marco/A-3773-2013; OI Pistis, Marco/0000-0002-4622-3205; Luchicchi, Antonio/0000-0002-0189-4347; Pillolla, Giuliano/0000-0002-6797-4905 FU Italian Ministry of University (PRIN 2005); Philip Morris USA; Philip Morris International; National Institute on Drug Abuse; National Institutes of Health; Department of Health and Human Services FX This work was supported by a grant from the Italian Ministry of University (PRIN 2005), Philip Morris USA and Philip Morris International, and by the Intramural Research Program of National Institute on Drug Abuse, National Institutes of Health, and Department of Health and Human Services. NR 57 TC 80 Z9 82 U1 0 U2 4 PU SOC NEUROSCIENCE PI WASHINGTON PA 11 DUPONT CIRCLE, NW, STE 500, WASHINGTON, DC 20036 USA SN 0270-6474 J9 J NEUROSCI JI J. Neurosci. PD DEC 17 PY 2008 VL 28 IS 51 BP 13985 EP 13994 DI 10.1523/JNEUROSCI.3221-08.2008 PG 10 WC Neurosciences SC Neurosciences & Neurology GA 384YM UT WOS:000261780100027 PM 19091987 ER PT J AU Yabroff, KR Bradley, CJ Mariotto, AB Brown, ML Feuer, EJ AF Yabroff, K. Robin Bradley, Cathy J. Mariotto, Angela B. Brown, Martin L. Feuer, Eric J. TI Estimates and Projections of Value of Life Lost From Cancer Deaths in the United States SO JOURNAL OF THE NATIONAL CANCER INSTITUTE LA English DT Article ID SERVICES TASK-FORCE; COLORECTAL-CANCER; ECONOMIC BURDEN; BREAST-CANCER; CALIFORNIA AB Value-of-life methods are increasingly used in policy analyses of the economic burden of disease. The purpose of this study was to estimate and project the value of life lost from cancer deaths in the United States. We estimated and projected US age-specific mortality rates for all cancers and for 16 types of cancer in men and 18 cancers in women in the years 2000-2020 and applied them to US population projections to estimate the number of deaths in each year. Cohort life tables were used to calculate the remaining life expectancy in the absence of cancer deaths-025EFthe person-years of life lost (PYLL). We used a willingness-to-pay approach in which the value of life lost due to cancer death was calculated by multiplying PYLL by an estimate of the value of 1 year of life ($150 000). We performed sensitivity analyses for female breast, colorectal, lung, and prostate cancers using varying assumptions about future cancer mortality rates through the year 2020. The value of life lost from all cancer deaths in the year 2000 was $960.6 billion; lung cancer alone represented more than 25% of this value. Projections for the year 2020 with current cancer mortality rates showed a 53% increase in the total value of life lost ($1472.5 billion). Projected annual decreases of cancer mortality rates of 2% reduced the expected value of life lost in the year 2020 from $121.0 billion to $80.7 billion for breast cancer, $140.1 billion to $93.5 billion for colorectal cancer, from $433.4 billion to $289.4 billion for lung cancer, and from $58.4 billion to $39.0 billion for prostate cancer. Estimated value of life lost due to cancer deaths in the United States is substantial and expected to increase dramatically, even if mortality rates remain constant, because of expected population changes. These estimates and projections may help target investments in cancer control strategies to tumor sites that are likely to result in the greatest burden of disease and to interventions that are the most cost-effective. C1 [Yabroff, K. Robin] NCI, Hlth Serv & Econ Branch, Appl Res Program, Div Canc Control & Populat Sci, Bethesda, MD 20892 USA. [Bradley, Cathy J.] Virginia Commonwealth Univ, Massey Canc Ctr, Richmond, VA USA. RP Yabroff, KR (reprint author), NCI, Hlth Serv & Econ Branch, Appl Res Program, Div Canc Control & Populat Sci, Execut Plaza N,Rm 4005,6130 Execut Blvd,MSC 7344, Bethesda, MD 20892 USA. EM yabroffr@mail.nih.gov OI Yabroff, K. Robin/0000-0003-0644-5572 NR 25 TC 51 Z9 51 U1 0 U2 10 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0027-8874 J9 J NATL CANCER I JI J. Natl. Cancer Inst. PD DEC 17 PY 2008 VL 100 IS 24 BP 1755 EP 1762 DI 10.1093/jnci/djn383 PG 8 WC Oncology SC Oncology GA 386SE UT WOS:000261902100010 PM 19066267 ER PT J AU Bradley, CJ Yabroff, KR Dahman, B Feuer, EJ Mariotto, A Brown, ML AF Bradley, Cathy J. Yabroff, K. Robin Dahman, Bassam Feuer, Eric J. Mariotto, Angela Brown, Martin L. TI Productivity Costs of Cancer Mortality in the United States: 2000-2020 SO JOURNAL OF THE NATIONAL CANCER INSTITUTE LA English DT Article ID US AB A model that predicts the economic benefit of reduced cancer mortality provides critical information for allocating scarce resources to the interventions with the greatest benefits. We developed models using the human capital approach, which relies on earnings as a measure of productivity, to estimate the value of productivity lost as a result of cancer mortality. The base model aggregated age- and sex-specific data from four primary sources: 1) the US Bureau of the Census, 2) US death certificate data for 1999-2003, 3) cohort life tables from the Berkeley Mortality Database for 1900-2000, and 4) the Bureau of Labor Statistics Current Population Survey. In a model that included costs of caregiving and household work, data from the National Human Activity Pattern Survey and the Caregiving in the U.S. study were used. Sensitivity analyses were performed using six types of cancer assuming a 1% decline in cancer mortality rates. The values of forgone earnings for employed individuals and imputed forgone earnings for informal caregiving were then estimated for the years 2000-2020. The annual productivity cost from cancer mortality in the base model was approximately $115.8 billion in 2000; the projected value was $147.6 billion for 2020. Death from lung cancer accounted for more than 27% of productivity costs. A 1% annual reduction in lung, colorectal, breast, leukemia, pancreatic, and brain cancer mortality lowered productivity costs by $814 million per year. Including imputed earnings lost due to caregiving and household activity increased the base model total productivity cost to $232.4 billion in 2000 and to $308 billion in 2020. Investments in programs that target the cancers with high incidence and/or cancers that occur in younger, working-age individuals are likely to yield the greatest reductions in productivity losses to society. C1 [Bradley, Cathy J.] Virginia Commonwealth Univ, Massey Canc Ctr, Dept Hlth Adm, Richmond, VA 23298 USA. [Dahman, Bassam] Virginia Commonwealth Univ, Div Qual Hlth Care, Dept Internal Med, Richmond, VA 23298 USA. [Yabroff, K. Robin; Brown, Martin L.] NCI, Hlth Serv & Econ Branch, Appl Res Program, Bethesda, MD 20892 USA. [Feuer, Eric J.; Mariotto, Angela] NCI, Stat Res & Applicat Branch, Surveillance Res Program, Bethesda, MD 20892 USA. RP Bradley, CJ (reprint author), Virginia Commonwealth Univ, Massey Canc Ctr, Dept Hlth Adm, 1008 E Clay St,POB 980203, Richmond, VA 23298 USA. EM cjbradley@vcu.edu OI Yabroff, K. Robin/0000-0003-0644-5572 FU National Cancer Institute FX This research was supported by National Cancer Institute contract with C. J. Bradley, PhD. NR 27 TC 83 Z9 83 U1 0 U2 11 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0027-8874 J9 J NATL CANCER I JI J. Natl. Cancer Inst. PD DEC 17 PY 2008 VL 100 IS 24 BP 1763 EP 1770 DI 10.1093/jnci/djn384 PG 8 WC Oncology SC Oncology GA 386SE UT WOS:000261902100011 PM 19066273 ER PT J AU Anderson, WF Rosenberg, PS Menashe, I Mitani, A Pfeiffer, RM AF Anderson, William F. Rosenberg, Philip S. Menashe, Idan Mitani, Aya Pfeiffer, Ruth M. TI Age-Related Crossover in Breast Cancer Incidence Rates Between Black and White Ethnic Groups SO JOURNAL OF THE NATIONAL CANCER INSTITUTE LA English DT Article ID BIRTH COHORT PATTERNS; CHRONIC DISEASE RATES; UNITED-STATES; RISK-FACTORS; TEMPORAL VARIATION; RECEPTOR STATUS; RECENT TRENDS; PERIOD; WOMEN; MODELS AB Although breast cancer incidence is higher in black women than in white women among women younger than 40 years, the reverse is true among those aged 40 years or older. This crossover in incidence rates between black and white ethnic groups has been well described, has not been completely understood, and has been viewed as an artifact. To quantify this incidence rate crossover, we examined data for 440 653 women with invasive breast cancer from the National Cancer Institute's Surveillance, Epidemiology, and End Results database from January 1, 1975, through December 31, 2004. Data on invasive female breast cancers were stratified by race, age at diagnosis, year of diagnosis, and tumor characteristics. Standard descriptive analyses were supplemented with Poisson regression models, age-period-cohort models, and two-component mixture models. All statistical tests were two-sided. We observed qualitative (ie, crossing or reversing) interactions between age and race. That is, age-specific incidence rates overall (expressed as number of breast cancers per 100 000 woman-years) were higher among black women (15.5) than among white women (13.1) younger than 40 years (difference = 2.4, 95% confidence interval [CI] = 2.4 to 2.4), and then, age-specific rates crossed with rates higher among white women (281.3) than among black women (239.5) aged 40 years or older (difference = 41.8, 95% CI = 41.7 to 41.9). The black-to-white incidence rate crossover was observed for all tumor characteristics assessed, although the crossover occurred at earlier ages of diagnosis for low-risk tumor characteristics than for high-risk tumor characteristics. The incidence rate crossover between ethnic groups was robust (ie, reliable and reproducible) to adjustment for calendar period and birth cohort effects in age-period-cohort models (P < .001 for difference by race). Although this ecologic study cannot determine the individual-level factors responsible for the racial crossover in vital rates, it confirms that the age-related crossover in breast cancer incidence rates between black and white ethnic groups is a robust age-specific effect that is independent of period and cohort effects. C1 [Anderson, William F.] NCI, Biostat Branch, Div Canc Epidemiol & Genet, NIH,US Dept HHS,EPS, Bethesda, MD 20892 USA. [Mitani, Aya] Yale Univ, Sch Med, Dept Epidemiol & Publ Hlth, New Haven, CT 06510 USA. RP Anderson, WF (reprint author), NCI, Biostat Branch, Div Canc Epidemiol & Genet, NIH,US Dept HHS,EPS, Rm 8036,6120 Execut Blvd, Bethesda, MD 20892 USA. EM wanderso@mail.nih.gov RI Pfeiffer, Ruth /F-4748-2011 FU National Institutes of Health; National Cancer Institute FX This research was supported in part by the Intramural Research Program of the National Institutes of Health, National Cancer Institute. NR 56 TC 67 Z9 67 U1 0 U2 1 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0027-8874 J9 J NATL CANCER I JI J. Natl. Cancer Inst. PD DEC 17 PY 2008 VL 100 IS 24 BP 1804 EP 1814 DI 10.1093/jnci/djn411 PG 11 WC Oncology SC Oncology GA 386SE UT WOS:000261902100015 PM 19066264 ER PT J AU Gustafson-Vickers, SL Lu, VB Lai, AY Todd, KG Ballanyi, K Smith, PA AF Gustafson-Vickers, Sabrina L. Lu, Van B. Lai, Aaron Y. Todd, Kathryn G. Ballanyi, Klaus Smith, Peter A. TI Long-term actions of interleukin-1 beta on delay and tonic firing neurons in rat superficial dorsal horn and their relevance to central sensitization SO MOLECULAR PAIN LA English DT Article ID SUBSTANTIA-GELATINOSA NEURONS; PRO-INFLAMMATORY CYTOKINES; PATHOLOGICAL PAIN STATES; PERIPHERAL-NERVE INJURY; NEUROPATHIC PAIN; SPINAL-CORD; PYRAMIDAL NEURONS; LAMINAE-I; MICE; SENSITIVITY AB Background: Cytokines such as interleukin 1 beta (IL-1 beta) have been implicated in the development of central sensitization that is characteristic of neuropathic pain. To examine its long-term effect on nociceptive processing, defined medium organotypic cultures of rat spinal cord were exposed to 100 pM IL-1 beta for 6-8 d. Interleukin effects in the dorsal horn were examined by whole-cell patch-clamp recording and Ca(2+) imaging techniques. Results: Examination of the cultures with confocal Fluo-4 AM imaging showed that IL-1 beta increased the change in intracellular Ca2+ produced by exposure to 35-50 mM K(+). This is consistent with a modest increase in overall dorsal horn excitability. Despite this, IL-1 beta did not have a direct effect on rheobase or resting membrane potential nor did it selectively destroy any specific neuronal population. All effects were instead confined to changes in synaptic transmission. A variety of pre- and postsynaptic actions of IL-1 beta were seen in five different electrophysiologically-defined neuronal phenotypes. In putative excitatory 'delay' neurons, cytokine treatment increased the amplitude of spontaneous EPSC's (sEPSC) and decreased the frequency of spontaneous IPSC's (sIPSC). These effects would be expected to increase dorsal horn excitability and to facilitate the transfer of nociceptive information. However, other actions of IL-1 beta included disinhibition of putative inhibitory 'tonic' neurons and an increase in the amplitude of sIPSC's in 'delay' neurons. Conclusion: Since spinal microglial activation peaks between 3 and 7 days after the initiation of chronic peripheral nerve injury and these cells release IL-1 beta at this time, our findings define some of the neurophysiological mechanisms whereby nerve-injury induced release of IL-1 beta may contribute to the central sensitization associated with chronic neuropathic pain. C1 [Ballanyi, Klaus; Smith, Peter A.] Univ Alberta, Ctr Neurosci, Edmonton, AB, Canada. [Ballanyi, Klaus; Smith, Peter A.] Univ Alberta, Dept Pharmacol, Edmonton, AB, Canada. [Ballanyi, Klaus; Smith, Peter A.] Univ Alberta, Dept Physiol, Edmonton, AB, Canada. [Lai, Aaron Y.; Todd, Kathryn G.] Univ Alberta, Dept Psychiat, Edmonton, AB, Canada. [Gustafson-Vickers, Sabrina L.] Univ British Columbia, Fac Med Class 2011, Vancouver, BC V6T 1Z3, Canada. [Lu, Van B.] NIAAA, Sect Transmitter Signaling, Lab Mol Physiol, NIH, Bethesda, MD 20892 USA. RP Smith, PA (reprint author), Univ Alberta, Ctr Neurosci, Edmonton, AB, Canada. EM sgv@interchange.ubc.ca; luvb@mail.nih.gov; aylai@ualberta.ca; kgtodd@ualberta.ca; klaus.ballanyi@ualberta.ca; peter.a.smith@ualberta.ca OI Lu, Van/0000-0002-4880-6455 FU Canadian Institutes of Health Research (CIHR) FX Supported by the Canadian Institutes of Health Research (CIHR). We thank Drs. W. F. Colmers and Q. Pittman for useful discussions. NR 43 TC 21 Z9 25 U1 0 U2 5 PU BIOMED CENTRAL LTD PI LONDON PA CURRENT SCIENCE GROUP, MIDDLESEX HOUSE, 34-42 CLEVELAND ST, LONDON W1T 4LB, ENGLAND SN 1744-8069 J9 MOL PAIN JI Mol. Pain PD DEC 17 PY 2008 VL 4 AR 63 DI 10.1186/1744-8069-4-63 PG 11 WC Neurosciences SC Neurosciences & Neurology GA 393WA UT WOS:000262406000001 PM 19091115 ER PT J AU Akashi, YJ Goldstein, DS Barbaro, G Ueyama, T AF Akashi, Yoshihiro J. Goldstein, David S. Barbaro, Giuseppe Ueyama, Takashi TI Takotsubo Cardiomyopathy A New Form of Acute, Reversible Heart Failure SO CIRCULATION LA English DT Article DE catecholamines; heart failure; nervous system, autonomic; stress; apical ballooning ID TAKO-TSUBO CARDIOMYOPATHY; LEFT-VENTRICULAR DYSFUNCTION; ACUTE MYOCARDIAL-INFARCTION; APICAL BALLOONING SYNDROME; EMOTIONAL-STRESS; OVARIECTOMIZED RATS; NERVOUS-SYSTEM; PLASMA-LEVELS; ANIMAL-MODEL; ESTROGEN C1 [Akashi, Yoshihiro J.] St Marianna Univ, Sch Med, Dept Internal Med, Div Cardiol,Miyamae Ku, Kawasaki, Kanagawa 2168511, Japan. [Goldstein, David S.] Natl Inst Neurol Disorders & Stroke, Clin Neurosci Program, Div Intramural Res, NIH, Bethesda, MD USA. [Barbaro, Giuseppe] Univ Roma La Sapienza, Dept Med Pathophysiol, Cardiol Unit, Rome, Italy. [Ueyama, Takashi] Wakayama Med Univ, Sch Med, Dept Anat & Cell Biol, Wakayama, Japan. RP Akashi, YJ (reprint author), St Marianna Univ, Sch Med, Dept Internal Med, Div Cardiol,Miyamae Ku, 2-16-1 Sugao, Kawasaki, Kanagawa 2168511, Japan. EM Johnny@marianna-u.ac.jp RI Akashi, Yoshihiro/E-5227-2011 OI Akashi, Yoshihiro/0000-0001-7670-7326 FU Intramural NIH HHS [Z01 NS003033-02] NR 51 TC 298 Z9 316 U1 6 U2 13 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD DEC 16 PY 2008 VL 118 IS 25 BP 2754 EP 2762 DI 10.1161/CIRCULATIONAHA.108.767012 PG 9 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 387JO UT WOS:000261948700013 PM 19106400 ER PT J AU Bluemke, DA Kronmal, RA Lima, JAC Liu, K Olson, J Burke, GL Folsom, AR AF Bluemke, David A. Kronmal, Richard A. Lima, Joao A. C. Liu, Kiang Olson, Jean Burke, Gregory L. Folsom, Aaron R. TI The Relationship of Left Ventricular Mass and Geometry to Incident Cardiovascular Events SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Article DE heart failure; stroke; coronary heart disease; epidemiology; magnetic resonance imaging; left ventricular hypertrophy ID CONGESTIVE-HEART-FAILURE; CORONARY-ARTERY-DISEASE; END-POINT REDUCTION; MAGNETIC-RESONANCE; 2-DIMENSIONAL ECHOCARDIOGRAPHY; PROGNOSTIC-SIGNIFICANCE; LOSARTAN INTERVENTION; SYSTEMIC HYPERTENSION; ELDERLY COHORT; BLOOD-PRESSURE AB Objective The purpose of this study was to evaluate the relationship of left ventricular (LV) mass and geometry measured with cardiac magnetic resonance imaging (MRI) to incident cardiovascular events in the MESA (Multi-Ethnic Study of Atherosclerosis) study. Background MRI is highly accurate for evaluation of heart size and structure and has not previously been used in a large epidemiologic study to predict cardiovascular events. Methods A total of 5,098 participants in the MESA study underwent cardiac MRI at the baseline examination and were followed up for a median of 4 years. Cox proportional hazard models were constructed to predict the end points of coronary heart disease (CHD), stroke, and heart failure (HF) after adjustment for cardiovascular risk factors. Results A total of 216 incident events were observed during the follow-up period. In adjusted models, the end points of incident CHD and stroke were positively associated with increased LV mass-to-volume ratio (CHD, hazard ratio [HR]: 2.1 per g/ml, p = 0.02; stroke, HR: 4.2 per g/ml, p = 0.005). In contrast, LV mass showed the strongest association with incident HF events (HR: 1.4 per 10% increment, p < 0.0001). The HF events occurred primarily in participants with LV hypertrophy, that is, >= 95th percentile of LV mass (HR: 8.6, 95% confidence interval: 3.7 to 19.9, reference group <50th percentile of LV mass). Conclusions The LV size was related to incident HF, stroke, and CHD in this multiethnic cohort. Whereas body size-adjusted LV mass alone predicted incident HF, concentric ventricular remodeling predicted incident stroke and CHD. (J Am Coll Cardiol 2008; 52: 2148-55) (C) 2008 by the American College of Cardiology Foundation C1 [Bluemke, David A.; Lima, Joao A. C.] Johns Hopkins Univ, Sch Med, Dept Radiol, Div Cardiol, Baltimore, MD 21205 USA. [Bluemke, David A.; Lima, Joao A. C.] Johns Hopkins Univ, Sch Med, Dept Radiol Sci, Div Cardiol, Baltimore, MD USA. [Bluemke, David A.; Lima, Joao A. C.] Johns Hopkins Univ, Sch Med, Dept Med, Div Cardiol, Baltimore, MD 21205 USA. [Kronmal, Richard A.] Univ Washington, Sch Publ Hlth & Community Med, Dept Biostat, Seattle, WA 98195 USA. [Liu, Kiang] Northwestern Univ, Feinberg Sch Med, Dept Prevent Med, Chicago, IL 60611 USA. [Olson, Jean] NHLBI, Div Prevent & Populat Sci, Bethesda, MD 20892 USA. [Burke, Gregory L.] Wake Forest Univ, Bowman Gray Sch Med, Dept Publ Hlth Sci, Winston Salem, NC 27103 USA. [Folsom, Aaron R.] Univ Minnesota, Sch Publ Hlth, Div Epidemiol & Community Hlth, Minneapolis, MN USA. RP Bluemke, DA (reprint author), NIH, Ctr Clin, Room 10-1C355, Bethesda, MD 20892 USA. EM bluemked@nih.gov OI Bluemke, David/0000-0002-8323-8086 FU MESA FX The authors thank the other investigators, the staff, and the participants of the MESA study for their valuable contributions. A full list of participating MESA study investigators and institutions can be found at http://www.mesa-nhlbi.org. NR 46 TC 222 Z9 226 U1 0 U2 5 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0735-1097 J9 J AM COLL CARDIOL JI J. Am. Coll. Cardiol. PD DEC 16 PY 2008 VL 52 IS 25 BP 2148 EP 2155 DI 10.1016/j.jacc.2008.09.014 PG 8 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 384PR UT WOS:000261757200005 PM 19095132 ER PT J AU Fleg, JL Mete, M Howard, BV Umans, JG Roman, MJ Ratner, RE Silverman, A Galloway, JM Henderson, JA Weir, MR Wilson, C Stylianou, M Howard, WJ AF Fleg, Jerome L. Mete, Mihriye Howard, Barabara V. Umans, Jason G. Roman, Mary J. Ratner, Robert E. Silverman, Angela Galloway, James M. Henderson, Jeffrey A. Weir, Matthew R. Wilson, Charlton Stylianou, Mario Howard, Wm. James TI Effect of Statins Alone Versus Statins Plus Ezetimibe on Carotid Atherosclerosis in Type 2 Diabetes SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Article DE ezetimibe; carotid artery intima-media thickness; atherosclerosis ID LDL CHOLESTEROL; BLOOD-PRESSURE; LOWER TARGETS; SIMVASTATIN; THERAPY; DISEASE; NIACIN; SANDS AB Objectives This secondary analysis from the SANDS (Stop Atherosclerosis in Native Diabetics Study) trial examines the effects of lowering low-density lipoprotein cholesterol (LDL-C) with statins alone versus statins plus ezetimibe on common carotid artery intima-media thickness (CIMT) in patients with type 2 diabetes and no prior cardiovascular event. Background It is unknown whether the addition of ezetimibe to statin therapy affects subclinical atherosclerosis. Methods Within an aggressive group (target LDL-C <= 70 mg/dl; non-high-density lipoprotein cholesterol <= 100 mg/dl; systolic blood pressure <= 115 mm Hg), change in CIMT over 36 months was compared in diabetic individuals >40 years of age receiving statins plus ezetimibe versus statins alone. The CIMT changes in both aggressive subgroups were compared with changes in the standard subgroups (target LDL-C <= 100 mg/dl; non-high-density lipoprotein cholesterol <= 130 mg/dl; systolic blood pressure <= 130 mm Hg). Results Mean (95% confidence intervals) LDL-C was reduced by 31 (23 to 37) mg/dl and 32 (27 to 38) mg/dl in the aggressive group receiving statins plus ezetimibe and statins alone, respectively, compared with changes of 1 (-3 to 6) mg/dl in the standard group (p < 0.0001) versus both aggressive subgroups. Within the aggressive group, mean CIMT at 36 months regressed from baseline similarly in the ezetimibe (-0.025 [-0.05 to 0.003] mm) and nonezetimibe subgroups (-0.012 [-0.03 to 0.008] mm) but progressed in the standard treatment arm (0.039 [0.02 to 0.06] mm), intergroup p < 0.0001. Conclusions Reducing LDL-C to aggressive targets resulted in similar regression of CIMT in patients who attained equivalent LDL-C reductions from a statin alone or statin plus ezetimibe. Common carotid artery IMT increased in those achieving standard targets. (Stop Atherosclerosis in Native Diabetics Study [SANDS]; NCT00047424) (J Am Coll Cardiol 2008; 52: 2198-205) (C) 2008 by the American College of Cardiology Foundation C1 [Fleg, Jerome L.; Stylianou, Mario] NHLBI, Bethesda, MD 20892 USA. [Fleg, Jerome L.; Mete, Mihriye; Howard, Barabara V.; Umans, Jason G.; Ratner, Robert E.; Silverman, Angela] MedStar Res Inst, Hyattsville, MD 20783 USA. [Roman, Mary J.] Weill Cornell Med Coll, New York, NY USA. [Galloway, James M.] Univ Arizona, Hlth Sci Ctr, Tucson, AZ USA. [Henderson, Jeffrey A.] Black Hills Ctr Amer Indian Hlth, Rapid City, SD USA. [Weir, Matthew R.] Univ Maryland, Sch Med, Baltimore, MD 21201 USA. [Wilson, Charlton] Phoenix Indian Med Ctr, Phoenix, AZ USA. [Howard, Wm. James] Washington Hosp Ctr, Washington, DC 20010 USA. RP Fleg, JL (reprint author), MedStar Res Inst, 6495 New Hampshire Ave, Hyattsville, MD 20783 USA. EM wm.james.howard@medstar.net FU NHLBI NIH HHS [U01 HL067031, U01 HL067031-01A1, 1U01 HL67031-01A1] NR 17 TC 149 Z9 162 U1 6 U2 10 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0735-1097 J9 J AM COLL CARDIOL JI J. Am. Coll. Cardiol. PD DEC 16 PY 2008 VL 52 IS 25 BP 2198 EP 2205 DI 10.1016/j.jacc.2008.10.031 PG 8 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 384PR UT WOS:000261757200012 PM 19095139 ER PT J AU Wei, Q Jiang, H Matthews, CP Colburn, NH AF Wei, Qiou Jiang, Hong Matthews, Connie P. Colburn, Nancy H. TI Sulfiredoxin is an AP-1 target gene that is required for transformation and shows elevated expression in human skin malignancies SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE skin tumor; tumor promotion; peroxiredoxin ID CYSTEINE-SULFINIC ACID; MOUSE EPIDERMAL-CELLS; C-JUN; 2-CYS PEROXIREDOXIN; OXIDATIVE STRESS; JB6 CELLS; MAMMALIAN SULFIREDOXIN; TUMOR PROMOTION; REDUCTION; PRODUCT AB Previous studies have shown that a dominant negative form of c-Jun (TAM67) suppresses mouse skin carcinogenesis both in vitro and in vivo. The current study identifies Sulfiredoxin (Srx) as a unique target of activator protein-1 (AP-1) activation and TAM67 inhibition. Manipulation of Srx levels by ShRNA or over-expression demonstrates that Srx is critical for redox homeostasis through reducing hyperoxidized peroxiredoxins. In JB6 cells, knockdown of Srx abolishes tumor promoter-induced transformation and enhances cell sensitivity to oxidative stress. Knockdown of Srx also impairs c-Jun phosphorylation, implicating a role for Srx in the feedback regulation of AP-1 activity. Screening of patient tissues by tissue microarray reveals elevated Srx expression in several types of human skin cancers. Our study indicates that Srx is a functionally significant target of AP-1 blockade that may have value in cancer prevention or treatment. C1 [Wei, Qiou; Jiang, Hong; Matthews, Connie P.; Colburn, Nancy H.] Natl Canc Inst, Lab Canc Prevent, Ctr Canc Res, Frederick, MD 21701 USA. RP Colburn, NH (reprint author), Natl Canc Inst, Lab Canc Prevent, Ctr Canc Res, Frederick, MD 21701 USA. EM colburn@ncifcrf.gov FU National Cancer Institute FX We thank Dr. Kenneth Tew for kindly providing reagents. We also thank Dr. Matthew Young and Ms. AlysonBakerfor helpwiththe mouse epidermis and JB6 models, and all other members of the Colburn laboratory for thoughtful discussions and suggestions. Q.W. is a recipient of the Cancer Research Training Award from the National Cancer Institute. This work was supported in part by the Intramural Research Program of the National Cancer Institute NR 42 TC 44 Z9 48 U1 0 U2 8 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD DEC 16 PY 2008 VL 105 IS 50 BP 19738 EP 19743 DI 10.1073/pnas.0810676105 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 385GI UT WOS:000261802300032 PM 19057013 ER PT J AU Catalfamo, M Di Mascio, M Hu, Z Srinivasula, S Thaker, V Adelsberger, J Rupert, A Baseler, M Tagaya, Y Roby, G Rehm, C Follmann, D Lane, HC AF Catalfamo, Marta Di Mascio, Michele Hu, Zonghui Srinivasula, Sharat Thaker, Vishakha Adelsberger, Joseph Rupert, Adam Baseler, Michael Tagaya, Yutaka Roby, Gregg Rehm, Catherine Follmann, Dean Lane, H. Clifford TI HIV infection-associated immune activation occurs by two distinct pathways that differentially affect CD4 and CD8 T cells SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE CD4 T cell homeostasis; IL-7; STAT-5 ID VIRUS TYPE-1 INFECTION; IMMUNODEFICIENCY-VIRUS; POTENTIAL ROLE; CENTRAL MEMORY; HLA-DR; LYMPHOCYTES; EXPRESSION; TURNOVER; HOMEOSTASIS; IL-7 AB HIV infection is characterized by a brisk immune activation that plays an important role in the CD4 depletion and immune dysfunction of patients with AIDS. The mechanism underlying this activation is poorly understood. In the current study, we tested the hypothesis that this activation is the net product of two distinct pathways: the inflammatory response to HIV infection and the homeostatic response to CD4 T cell depletion. Using ex vivo BrdU incorporation of PBMCs from 284 patients with different stages of HIV infection, we found that CD4 proliferation was better predicted by the combination of CD4 depletion and HIV viral load (R(2) = 0.375, P < 0.001) than by either parameter alone (CD4 T cell counts, R(2) = 0.202, P < 0.001; HIV viremia, R(2) = 0.302, P < 0.001). Interestingly, CD8 T cell proliferation could be predicted by HIV RNA levels alone (R(2) = 0.334, P < 0.001) and this predictive value increased only slightly (R(2) = 0.346, P < 0.001) when CD4 T cell depletion was taken into account. Consistent with the hypothesis that CD4 T cell proliferation is driven by IL-7 as a homeostatic response to CD4 T cell depletion, levels of phosphorylated STAT-5 were found to be elevated in naive subsets of CD4 and CD8 T cells from patients with HIV infection and in the central memory subset of CD4 T cells. Taken together these data demonstrate that at least two different pathways lead to immune activation of T cells in patients with HIV infection and these pathways differentially influence CD4 and CD8 T cell subsets. C1 [Catalfamo, Marta; Thaker, Vishakha; Roby, Gregg; Rehm, Catherine; Lane, H. Clifford] NIAID, Clin & Mol Retrovirol Sect, Immunoregulat Lab, NIH, Bethesda, MD 20892 USA. [Di Mascio, Michele; Hu, Zonghui; Follmann, Dean] NIAID, Biostat Res Branch, Bethesda, MD 20892 USA. [Adelsberger, Joseph; Rupert, Adam; Baseler, Michael] Sci Applicat Int Corp, AIDS Monitoring Labs, Frederick, MD 21702 USA. [Srinivasula, Sharat] Sci Applicat Int Corp, Biostat Res Branch, Frederick, MD 21702 USA. [Tagaya, Yutaka] NCI, Metab Branch, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. RP Catalfamo, M (reprint author), NIAID, Clin & Mol Retrovirol Sect, Immunoregulat Lab, NIH, Bldg 10,Room 7N246,9000 Rockville Pike, Bethesda, MD 20892 USA. EM catalfam@niaid.nih.gov FU Intramural Research Program of the National Institute of Allergy and Infectious Diseases; National Institutes of Health; National Cancer Institute [N01-CO-12400] FX We thank the patients of the National Institute of Allergy and Infectious Diseases HIV-Clinic for their participation in this study, the normal volunteers of the National Institutes of Health Blood Bank, and Dr. Anthony Fauci for his guidance and support. This work was supported by the Intramural Research Program of the National Institute of Allergy and Infectious Diseases, National Institutes of Health; National Cancer Institute, National Institutes of Health Contract N01-CO-12400 (to Science Applications International). NR 39 TC 82 Z9 84 U1 0 U2 5 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD DEC 16 PY 2008 VL 105 IS 50 BP 19851 EP 19856 DI 10.1073/pnas.0810032105 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 385GI UT WOS:000261802300051 PM 19060209 ER PT J AU Peddada, SD Laughlin, SK Miner, K Guyon, JP Haneke, K Vahdat, HL Semelka, RC Kowalik, A Armao, D Davis, B Baird, DD AF Peddada, Shyamal D. Laughlin, Shannon K. Miner, Kelly Guyon, Jean-Philippe Haneke, Karen Vahdat, Heather L. Semelka, Richard C. Kowalik, Ania Armao, Diane Davis, Barbara Baird, Donna Day TI Growth of uterine leiomyomata among premenopausal black and white women SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE ethnic; fibroid; MRI; tumor growth; longitudinal data ID NATURAL-HISTORY; UNITED-STATES; TUMOR SIZE; FIBROIDS; EXPRESSION; GENE; AGE; INACTIVATION; HYSTERECTOMY; DIAGNOSIS AB Uterine leiomyomata (fibroids) are the leading cause of hysterectomy in the United States. Black women have a greater fibroid burden than whites, yet no study has systematically evaluated the growth of fibroids in blacks and whites. We prospectively tracked growth for 262 fibroids (size range: 1-13 cm in diameter) from 72 premenopausal participants (38 blacks and 34 whites). Fibroid volume was measured by computerized analysis of up to four MRI scans over 12 months. We used mixed effects models to identify factors that are associated with growth, and results were converted to percent change per 6 months for clinical relevance. The median growth rate was 9% (range: -89% to +138%). Seven percent of fibroids regressed (> 20% shrinkage). Tumors from the same woman grew at different rates (within-woman component of variation was twice the component among women; both were significant, P < 0.001). Black and white women less than 35 years of age had similar fibroid growth rates. However, growth rates declined with age for whites but not for blacks (P = 0.05). The odds of a tumor growing more than 20% in 6 months also decreased with age for whites but not for blacks (P < 0.01). Growth rates were not influenced by tumor size, location, body mass index, or parity. We conclude that (i) spontaneous regression of fibroids occurs; (ii) fibroids from the same woman grow at different rates, despite a uniform hormonal milieu; (iii) fibroid size does not predict growth rate; and (iv) age-related differences in fibroid growth between blacks and whites may contribute to the higher symptom burden for black women. C1 [Laughlin, Shannon K.; Baird, Donna Day] NIEHS, Epidemiol Branch, Res Triangle Pk, NC 27709 USA. [Peddada, Shyamal D.; Miner, Kelly] NIEHS, Biostat Branch, Res Triangle Pk, NC 27709 USA. [Guyon, Jean-Philippe; Haneke, Karen; Vahdat, Heather L.] Integrated Syst Lab, Durham, NC 27713 USA. [Semelka, Richard C.; Armao, Diane] Univ N Carolina, Dept Radiol, Chapel Hill, NC 27599 USA. [Kowalik, Ania] Univ N Carolina, Dept Obstet Gynecol, Chapel Hill, NC 27599 USA. [Davis, Barbara] NIEHS, Lab Womens Hlth, Res Triangle Pk, NC 27709 USA. RP Baird, DD (reprint author), NIEHS, Epidemiol Branch, Res Triangle Pk, NC 27709 USA. EM baird@niehs.nih.gov RI Peddada, Shyamal/D-1278-2012; Baird, Donna/D-5214-2017 OI Baird, Donna/0000-0002-5544-2653 FU Intramural Research Program of the NIEHS; National Institutes of Health [Z01ES 101663-05]; National Center on Minority Health and Health Disparities [MO1RR00046]; NIEHS [N01-ES-95446, 27301-C-0157] FX The authors thank study participants; Ms. Edelstein (National Institute on Environmental and Health Sciences [NIEHS]) for graphics; Ms. Greasby (Graduate Student, Department of Biostatistics, University of California, Davis) for initial data quality control checks; Ms. Firat (Radiology Technician, University of North Carolina, Chapel Hill); Mss. Daniel, Davis, and Pope for managing radiology films and digital images (all at Integrated Laboratory Systems); and Ms. Ragan and Drs. Kissling, Korach, Weinberg, and Wilcox (NIEHS) and Dr. Leppert (Duke University) for reviewing an earlier version of the manuscript. Research was supported by the Intramural Research Program of the NIEHS, National Institutes of Health (Grant Z01ES 101663-05), with partial funding from the National Center on Minority Health and Health Disparities Grant MO1RR00046 and NIEHS Contracts N01-ES-95446 and 27301-C-0157. NR 32 TC 110 Z9 114 U1 0 U2 4 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD DEC 16 PY 2008 VL 105 IS 50 BP 19887 EP 19892 DI 10.1073/pnas.0808188105 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 385GI UT WOS:000261802300057 PM 19047643 ER PT J AU Nofsinger, RR Li, P Hong, SH Jonker, JW Barish, GD Ying, H Cheng, SY LeBlanc, M Xu, W Pei, LM Kang, YJ Nelson, M Downes, M Yu, RT Olefsky, JM Lee, CH Evans, RM AF Nofsinger, Russell R. Li, Pingping Hong, Suk-Hyun Jonker, Johan W. Barish, Grant D. Ying, Hao Cheng, Sheue-Yann LeBlanc, Mathias Xu, Wei Pei, Liming Kang, Yeon-Joo Nelson, Michael Downes, Michael Yu, Ruth T. Olefsky, Jerrold M. Lee, Chih-Hao Evans, Ronald M. TI SMRT repression of nuclear receptors controls the adipogenic set point and metabolic homeostasis SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE adipogenesis; corepressor; PPAR; TR; glucose regulation ID TRANSCRIPTIONAL COREPRESSOR RIP140; PPAR-GAMMA; ADAPTIVE THERMOGENESIS; OXIDATIVE-METABOLISM; HORMONE-RECEPTORS; ENERGY-BALANCE; ADIPOCYTES; COACTIVATOR; COMPLEXES; COFACTOR AB The nuclear receptor corepressor, silencing mediator of retinoid and thyroid hormone receptors (SMRT), is recruited by a plethora of transcription factors to mediate lineage and signal-dependent transcriptional repression. We generated a knockin mutation in the receptor interaction domain (RID) of SMRT (SMRT(mRID)) that solely disrupts its interaction with nuclear hormone receptors (NHRs). SMRTmRID mice are viable and exhibit no gross developmental abnormalities, demonstrating that the reported lethality of SMRT knockouts is determined by non-NHR transcription factors. However, SMRTmRID mice exhibit widespread metabolic defects including reduced respiration, altered insulin sensitivity, and 70% increased adiposity. The latter phenotype is illustrated by the observation that SMRT(mRID)-derived MEFs display a dramatically increased adipogenic capacity and accelerated differentiation rate. Collectively, our results demonstrate that SMRT-RID-dependent repression is a key determinant of the adipogenic set point as well as an integrator of glucose metabolism and whole-body metabolic homeostasis. C1 [Nofsinger, Russell R.; Hong, Suk-Hyun; Jonker, Johan W.; Barish, Grant D.; LeBlanc, Mathias; Pei, Liming; Nelson, Michael; Downes, Michael; Yu, Ruth T.; Evans, Ronald M.] Salk Inst Biol Studies, Gene Express Lab, La Jolla, CA 92037 USA. [Li, Pingping; Olefsky, Jerrold M.] Univ Calif San Diego, Dept Med, La Jolla, CA 92093 USA. [Ying, Hao; Cheng, Sheue-Yann] NCI, Mol Biol Lab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. [Xu, Wei] Univ Wisconsin, McArdle Lab Canc Res, Madison, WI 53706 USA. [Kang, Yeon-Joo] Burnham Inst Med REs, Ctr Neurosci Aging & Stem Cell Res, La Jolla, CA 92037 USA. [Lee, Chih-Hao] Harvard Univ, Sch Publ Hlth, Dept Genet & Complex Dis, Boston, MA 02115 USA. [Evans, Ronald M.] Salk Inst Biol Studies, Howard Hughes Med Inst, La Jolla, CA 92037 USA. RP Evans, RM (reprint author), Salk Inst Biol Studies, Gene Express Lab, 10010 N Torrey Pines Rd, La Jolla, CA 92037 USA. EM evans@salk.edu OI Jonker, Johan/0000-0002-3919-5437 FU Molecular Cardiology Training Grant [T32 HL07770-14]; Human Frontier Science Program; American Heart Association and American Diabetes Association; National Institutes of Health [R01DK075046]; Howard Hughes Medical Institute and National Institutes of Health [5R37DK057978, 5R01HD027183] FX We thank E. Banayo, H. Juguilon, J. Alvarez, and Y. Zou for technical assistance; J. Wong for anti-SMRT antibody; and E. Ong and S. Ganley for administrative assistance. R.R.N. was supported by Molecular Cardiology Training Grant T32 HL07770-14. J. W. J. is supported by a Human Frontier Science Program fellowship. C-H. L. is supported by the American Heart Association and American Diabetes Association and National Institutes of Health Grant R01DK075046. R. M. E. is an investigator of the Howard Hughes Medical Institute at the Salk Institute for Biological Studies and March of Dimes Chair in Molecular and Developmental Biology. This work was supported by the Howard Hughes Medical Institute and National Institutes of Health Grants 5R37DK057978 and 5R01HD027183. NR 27 TC 57 Z9 59 U1 0 U2 0 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 16 PY 2008 VL 105 IS 50 BP 20021 EP 20026 DI 10.1073/pnas.0811012105 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 385GI UT WOS:000261802300080 PM 19066220 ER PT J AU Logroscino, G Gao, X Chen, HL Wing, A Ascherio, A AF Logroscino, Giancarlo Gao, Xiang Chen, Honglei Wing, Al Ascherio, Alberto TI Dietary Iron Intake and Risk of Parkinson's Disease SO AMERICAN JOURNAL OF EPIDEMIOLOGY LA English DT Article DE ascorbic acid; diet; heme; iron; Parkinson disease; prospective studies ID FOOD FREQUENCY QUESTIONNAIRE; SUBSTANTIA-NIGRA; HUMAN BRAIN; VITAMIN-C; MEN; WOMEN; ACCUMULATION; CAROTENOIDS; MANGANESE; FERRITIN AB Dietary iron is the most important source of iron stores. Several case-control studies have described the association of high dietary iron and Parkinson's disease, but prospective data are lacking. The authors prospectively followed 47,406 men and 76,947 women from the United States who provided information through a mailed questionnaire on their diet, medical history, and lifestyle practices between 1984 and 2000. The authors documented 422 new cases of Parkinson's disease. Total iron intake was not associated with an increased risk of Parkinson's disease (relative risk (RR) = 1.10, 95% confidence interval (CI): 0.74, 1.65; P(trend) = 0.84), but dietary nonheme iron intake from food was associated with a 30% increased risk of Parkinson's disease (RR = 1.27, 95% CI: 0.92, 1.76; P(trend) = 0.02). A secondary analysis revealed that Parkinson's disease risk was significantly increased among individuals with high nonheme iron and low vitamin C intakes (RR = 1.92, 95% CI: 1.14, 3.32; P(trend) = 0.002). Supplemental iron intake was associated with a borderline increase in Parkinson's disease risk among men. Although the authors' prospective data did not support an association between total iron intake (dietary and supplemental) and risk of Parkinson's disease, a 30% increased risk was associated with a diet rich in nonheme iron. This increase in risk was present in those who had low vitamin C intake. C1 [Logroscino, Giancarlo] Univ Bari, Sch Med, Dept Neurol & Psychiat, Bari, Italy. [Ascherio, Alberto] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. [Gao, Xiang; Wing, Al; Ascherio, Alberto] Harvard Univ, Sch Publ Hlth, Dept Nutr, Boston, MA 02115 USA. [Logroscino, Giancarlo] Harvard Univ, Sch Med, Div Aging, Boston, MA 02115 USA. [Ascherio, Alberto] Brigham & Womens Hosp, Dept Med, Channing Lab, Boston, MA USA. [Chen, Honglei] NIEHS, Epidemiol Branch, Res Triangle Pk, NC 27709 USA. RP Logroscino, G (reprint author), Univ Bari, Sch Med, Dept Neurol & Psychiat, Bari, Italy. EM giancarlo.logroscino@neurol.uniba.it RI LOGROSCINO, GIANCARLO/K-5148-2016; OI LOGROSCINO, GIANCARLO/0000-0003-0423-3242; Chen, Honglei/0000-0003-3446-7779 FU Michael J. Fox Foundation; Kinetics Foundation; National Institutes of Health; National Institute of Environmental Health Sciences FX The work presented in this manuscript was supported in part by grants from the Michael J. Fox Foundation and the Kinetics Foundation. Dr. Chen is supported by the Intramural Research Program of the National Institutes of Health and the National Institute of Environmental Health Sciences. NR 44 TC 32 Z9 33 U1 1 U2 7 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 2008 VL 168 IS 12 BP 1381 EP 1388 DI 10.1093/aje/kwn273 PG 8 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 383OO UT WOS:000261683100006 PM 18945687 ER PT J AU Namiki, T Valencia, JC Hall, MD Hearing, VJ AF Namiki, Takeshi Valencia, Julio C. Hall, Matthew D. Hearing, Vincent J. TI A novel approach to enhance antibody sensitivity and specificity by peptide cross-linking SO ANALYTICAL BIOCHEMISTRY LA English DT Article DE Western blot; Antibody; Sensitivity; Specificity; Biuret reaction ID PROTEIN; MELANOCYTES; TYROSINASE; TRANSPORT AB Most current techniques employed to improve antigen-antibody signals in Western blotting and in immunohistochemistry rely on sample processing prior to staining (e.g., microwaving) or using a more robust reporter (e.g., a secondary antibody with biotin-streptavidin). We have developed and optimized a new approach intended to stabilize the complexes formed between antigens and their respective primary antibodies by cupric ions at high pH. This technique improves the affinity and lowers cross-reactivity with nonspecific bands of approximately 20% of antibodies tested (5/25). Here we report that this method can enhance antigen-antibody specificity and can improve the utility of some poorly reactive primary antibodies. Published by Elsevier Inc. C1 [Namiki, Takeshi; Valencia, Julio C.; Hall, Matthew D.; Hearing, Vincent J.] NCI, Cell Biol Lab, NIH, Bethesda, MD 20814 USA. RP Hearing, VJ (reprint author), NCI, Cell Biol Lab, NIH, Bldg 37,Room 3132, Bethesda, MD 20814 USA. EM hearingv@nih.gov RI Hall, Matthew/B-2132-2010 FU National Cancer Institute at the National Institutes of Health FX This research was supported by the Intramural Research Program of the National Cancer Institute at the National Institutes of Health. We thank Michael M. Gottesman (Bethesda, MD, USA), Steve Wilson (Bedfordshire, UK), and Nancy Mangini (Gary, IN, USA) for the gifts of antibodies to ABCB5, NCKX5, and SLC24A5, respectively. NR 17 TC 2 Z9 2 U1 1 U2 3 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0003-2697 J9 ANAL BIOCHEM JI Anal. Biochem. PD DEC 15 PY 2008 VL 383 IS 2 BP 265 EP 269 DI 10.1016/j.ab.2008.08.024 PG 5 WC Biochemical Research Methods; Biochemistry & Molecular Biology; Chemistry, Analytical SC Biochemistry & Molecular Biology; Chemistry GA 372KQ UT WOS:000260900900018 PM 18801330 ER PT J AU Ward, MM AF Ward, Michael M. TI Interpreting Studies of Cardiovascular Mortality in Rheumatoid Arthritis: The Importance of Timing SO ARTHRITIS & RHEUMATISM-ARTHRITIS CARE & RESEARCH LA English DT Editorial Material ID INFLAMMATORY POLYARTHRITIS; MYOCARDIAL-INFARCTION; DISEASE ONSET; COHORT; REGISTER; PREDICTS C1 [Ward, Michael M.] NIAMSD, NIH, Bethesda, MD 20892 USA. RP Ward, MM (reprint author), Bldg 10,Room 9S205,10 Ctr Dr,MSC 1828, Bethesda, MD 20892 USA. EM wardm1@mail.nih.gov FU Intramural NIH HHS [Z01 AR041153-04] NR 21 TC 8 Z9 8 U1 0 U2 0 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0004-3591 J9 ARTHRIT RHEUM-ARTHR JI Arthritis Rheum-Arthritis Care Res. PD DEC 15 PY 2008 VL 59 IS 12 BP 1687 EP 1689 DI 10.1002/art.24170 PG 3 WC Rheumatology SC Rheumatology GA 382DW UT WOS:000261586300001 PM 19035434 ER PT J AU Angers, M Uldry, M Kong, D Gimble, JM Jetten, AM AF Angers, Martin Uldry, Marc Kong, Dong Gimble, Jeffrey M. Jetten, Anton M. TI Mfsd2a encodes a novel major facilitator superfamily domain-containing protein highly induced in brown adipose tissue during fasting and adaptive thermogenesis SO BIOCHEMICAL JOURNAL LA English DT Article DE beta-adrenergic receptor (beta AR); brown adipose tissue (BAT); permease; symporter; thermogenesis ID DIET-INDUCED THERMOGENESIS; BETA-ADRENERGIC-RECEPTORS; ESCHERICHIA-COLI; MELIBIOSE PERMEASE; ENERGY-EXPENDITURE; MEMBRANE TOPOLOGY; TRANSPORTERS; FAMILY; ALPHA; COACTIVATORS AB This study describes the identification of Mfsd2a (major facilitator superfamily domain-containing protein 2a), a novel mammalian major facilitator superfamily domain-containing protein, and ail additional closely related protein, Mfsd2b. Most intron/exon junctions are conserved between the two genes, suggesting that they are derived from a common ancestor. Mfsd2a and Mfsd2b share a 12 transmembrane alpha-helical domain structure that bears greatest similarity to that of the bacterial Na(+)/melibiose symporters. Confocal microscopy demonstrated that Mfsd2a localizes to the endoplasmic reticulum. Mfsd2a is expressed in many tissues and is highly induced in liver and BAT (brown adipose tissue) during fasting. Mfsd2a displays an oscillatory expression profile in BAT and liver, consistent with a circadian rhythm. Although the basal level of Mfsd2a expression is relatively low in mouse BAT, it is greatly induced during cold-induced thermogenesis and after treatment with beta AR (beta-adrenergic receptor) agonists. This induction is totally abolished in beta-less (beta AR-deficient) mice. These findings indicate that Mfsd2a is greatly up-regulated in BAT during thermogenesis and that its induction is controlled by the beta AR signalling pathway. The observed induction of Mfsd2a expression in cultured BAT cells by dibutyryl-cAMP is in agreement with this conclusion. The present study suggests that Mfsd2a plays a role in adaptive thermogenesis. C1 [Angers, Martin; Jetten, Anton M.] NIEHS, Cell Biol Sect, LRB, Div Intramural Res,NIH, Res Triangle Pk, NC 27709 USA. [Uldry, Marc] Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. [Kong, Dong] Beth Israel Deaconess Med Ctr, Dept Med, Div Endocrinol, Boston, MA 02115 USA. [Gimble, Jeffrey M.] Louisiana State Univ Syst, Pennington Biomed Res Ctr, Stem Cell Lab, Baton Rouge, LA 70808 USA. RP Jetten, AM (reprint author), NIEHS, Cell Biol Sect, LRB, Div Intramural Res,NIH, 111 TW Alexander Dr, Res Triangle Pk, NC 27709 USA. EM jetten@niehs.nih.gov OI Jetten, Anton/0000-0003-0954-4445 FU NIEHS (National Institute of Environmental Health Sciences); NIH (National Institutes of Health) [Z01-ES-101586]; CNRU (Clinical Nutrition Research Unit) Center [1P30 DK072476]; NIDDK (National Institute of Diabetes and Digestive and Kidney Disease) FX We thank Or John Pritchard and Or Jennifer Perry for their valuable comments on the manuscript, Laura Miller for her assistance with the mice and Or Xiying Wu for his assistance with the circadian rhythm analysis. This research was supported by the Intramural Research Program of the NIEHS (National Institute of Environmental Health Sciences), NIH (National Institutes of Health) (Z01-ES-101586 awarded to A. M.J.) and by a CNRU (Clinical Nutrition Research Unit) Center Grant 1P30 DK072476 entitled 'Nutritional Programming: Environmental and Molecular Interactions' sponsored by the NIDDK (National Institute of Diabetes and Digestive and Kidney Disease) (awarded to J.M.G.). NR 34 TC 21 Z9 25 U1 0 U2 5 PU PORTLAND PRESS LTD PI LONDON PA THIRD FLOOR, EAGLE HOUSE, 16 PROCTER STREET, LONDON WC1V 6 NX, ENGLAND SN 0264-6021 J9 BIOCHEM J JI Biochem. J. PD DEC 15 PY 2008 VL 416 BP 347 EP 355 DI 10.1042/BJ20080165 PG 9 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 384ZA UT WOS:000261781500004 PM 18694395 ER PT J AU Wang, LL Li, Y Hu, P Teng, CT AF Wang, Liangli Li, Yin Hu, Peng Teng, Christina T. TI PGC-1 alpha induces dynamic protein interactions on the ERR alpha gene multi-hormone response element nucleosome in kidney cells SO BIOCHEMICAL JOURNAL LA English DT Article DE chromatin immunoprecipitation (ChIP); co-regulator; human kidney HK2 cell; oestrogen-related receptor (ERR) alpha and gamma; nucleosome; peroxisome proliferator-activated receptor-gamma coactivator-1 alpha (PGC-1 alpha) ID ESTROGEN-RELATED RECEPTOR; TRANSCRIPTIONAL COACTIVATOR PGC-1; ORPHAN NUCLEAR RECEPTORS; HUMAN LACTOFERRIN GENE; CHAIN ACYL-COENZYME; HISTONE ACETYLATION; ANDROGEN RECEPTOR; SKELETAL-MUSCLE; EXPRESSION; GAMMA AB ERR (oestrogen-related receptor)-alpha modulates the oestrogen signalling pathway and regulates genes participating in the physiological energy balance programme. Oestrogen and PGC-1 alpha (peroxisome proliferator-activated receptor-gamma coactivator-1 alpha), the master regulator of the energy homoeostasis programme, both regulate the expression of ERR alpha through the MHRE (multi-hormone response element) of the ERR alpha gene. Although the molecular mechanism of oestrogen action on ERR alpha regulation is well characterized, the mechanism of PGC-1 alpha induction is unclear. In this study, we examine chromatin Structural changes and protein interactions at the MHRE nucleosome in response to PGC-1 alpha expression in HK2 human kidney cells. We mapped the nucleosome positions of the ERR alpha gene promoter and examined the changes of historic acetylation in response to PGC-1 alpha expression. The interactions of DNA-binding proteins, ERR alpha and ERR gamma. co-activators {CBP [CREB (cAMP-response-element-binding protein)-binding protein], p300, PCAF (p300/CBP-associated factor)}, co-repressor [RIP140 (receptor-interacting protein of 140kDa)] and RNA polymerase II at the MHRE nucleosome region were investigated over time before and after PGC-1 alpha expression in the HK2 cells. We found a dynamic cyclic interaction of these proteins shortly after PGC-1 alpha expression and a slower cycling interaction, with fewer proteins involved, 20 h later. By Using the siRNA (small interfering RNA) knockdown approach, we discovered that ERR gamma was involved in the initial phase, but not in the later phase, of PGC-1 alpha-induced ERR alpha expression. C1 [Wang, Liangli; Li, Yin; Hu, Peng; Teng, Christina T.] NIEHS, Gene Regulat Sect, Reprod & Dev Toxicol Lab, NIH, Res Triangle Pk, NC 27709 USA. RP Teng, CT (reprint author), NIEHS, Gene Regulat Sect, Reprod & Dev Toxicol Lab, NIH, Res Triangle Pk, NC 27709 USA. EM teng1@niehs.nih.gov FU NIH (National Institutes of Health); NIEHS (National Institute of Environmental Health Sciences) FX This research was supported by the Intramural Research Program of NIH (National Institutes of Health), the NIEHS (National Institute of Environmental Health Sciences). We acknowledge Dr P. Hebbar and Dr M. Fatemi [LMC (Laboratory of Molecular Carcinogenesis), NIEHS] for helpful discussions throughout this study. We thank Dr Leping Li (Biostatistics, NIEHS) for performing the comparative sequence analysis. We also thank Dr A. Kralli (Scripps Laboratory, CA, U.S.A.) for providing the PGC-1 alpha adeno-virus construct. We appreciate the critical reading of the manuscript and valuable comments by Dr P. A. Wade and Dr K. Adelman (LMC, NIEHS). This paper was edited by Dr Peggy Kaminski. NR 41 TC 7 Z9 7 U1 0 U2 1 PU PORTLAND PRESS LTD PI LONDON PA CHARLES DARWIN HOUSE, 12 ROGER STREET, LONDON WC1N 2JU, ENGLAND SN 0264-6021 EI 1470-8728 J9 BIOCHEM J JI Biochem. J. PD DEC 15 PY 2008 VL 416 BP 407 EP 419 DI 10.1042/BJ20081085 PN 3 PG 13 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 384ZA UT WOS:000261781500010 PM 18673300 ER PT J AU Johnson, AD Handsaker, RE Pulit, SL Nizzari, MM O'Donnell, CJ de Bakker, PIW AF Johnson, Andrew D. Handsaker, Robert E. Pulit, Sara L. Nizzari, Marcia M. O'Donnell, Christopher J. de Bakker, Paul I. W. TI SNAP: a web-based tool for identification and annotation of proxy SNPs using HapMap SO BIOINFORMATICS LA English DT Article ID GENOME-WIDE ASSOCIATION; LOCI AB The interpretation of genome-wide association results is confounded by linkage disequilibrium between nearby alleles. We have developed a flexible bioinformatics query tool for single-nucleotide polymorphisms (SNPs) to identify and to annotate nearby SNPs in linkage disequilibrium (proxies) based on HapMap. By offering functionality to generate graphical plots for these data, the SNAP server will facilitate interpretation and comparison of genome-wide association study results, and the design of fine-mapping experiments (by delineating genomic regions harboring associated variants and their proxies). C1 [Handsaker, Robert E.; Nizzari, Marcia M.; de Bakker, Paul I. W.] MIT, Broad Inst, Cambridge, MA 02142 USA. [Handsaker, Robert E.; Nizzari, Marcia M.; de Bakker, Paul I. W.] Harvard Univ, Cambridge, MA 02142 USA. [Johnson, Andrew D.; O'Donnell, Christopher J.] NHLBI, Framingham Heart Study, NIH, Framingham, MA 01702 USA. [Johnson, Andrew D.; O'Donnell, Christopher J.] Boston Univ, Sch Med, Framingham, MA 01702 USA. [Pulit, Sara L.; de Bakker, Paul I. W.] Brigham & Womens Hosp, Dept Med, Div Genet, Boston, MA 02215 USA. [Pulit, Sara L.; de Bakker, Paul I. W.] Harvard Univ, Sch Med, Partners HealthCare Ctr Genet & Genom, Boston, MA 02215 USA. [O'Donnell, Christopher J.] Massachusetts Gen Hosp, Div Cardiol, Boston, MA 02114 USA. RP de Bakker, PIW (reprint author), MIT, Broad Inst, Cambridge, MA 02142 USA. EM debakker@broad.mit.edu RI Johnson, Andrew/G-6520-2013; de Bakker, Paul/B-8730-2009 OI de Bakker, Paul/0000-0001-7735-7858 FU NHLBI's Framingham Heart Study [N01-HC-25195]; NHLBI CARe (Candidate Gene Association Resource) [N01-HC-65226]; Intramural training program of the NHLBI FX Funding: NHLBI's Framingham Heart Study (N01-HC-25195 to A. D. J.); Intramural training program of the NHLBI (to A. D. J.); NHLBI CARe (Candidate Gene Association Resource) grant (N01-HC-65226 to R. E. H.). NR 9 TC 677 Z9 683 U1 1 U2 16 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 2008 VL 24 IS 24 BP 2938 EP 2939 DI 10.1093/bioinformatics/btn564 PG 2 WC Biochemical Research Methods; Biotechnology & Applied Microbiology; Computer Science, Interdisciplinary Applications; Mathematical & Computational Biology; Statistics & Probability SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Computer Science; Mathematical & Computational Biology; Mathematics GA 380HL UT WOS:000261456700026 PM 18974171 ER PT J AU Naoz, M Manor, U Sakaguchi, H Kachar, B Gov, NS AF Naoz, Moshe Manor, Uri Sakaguchi, Hirofumi Kachar, Bechara Gov, Nir S. TI Protein Localization by Actin Treadmilling and Molecular Motors Regulates Stereocilia Shape and Treadmilling Rate SO BIOPHYSICAL JOURNAL LA English DT Article ID HAIR-CELL STEREOCILIA; ENA/VASP PROTEINS; FILOPODIA FORMATION; ARP2/3 COMPLEX; MYOSIN-VI; MOTILITY; FILAMENTS; DYNAMICS; GROWTH; ORGANIZATION AB We present a physical model that describes the active localization of actin-regulating proteins inside stereocilia during steady-state conditions. The mechanism of localization is through the interplay of free diffusion and directed motion, which is driven by coupling to the treadmilling actin. laments and to myosin motors that move along the actin. laments. The resulting localization of both the molecular motors and their cargo is calculated, and is found to have an exponential (or steeper) profile. This localization can be at the base (driven by actin retrograde flow and minus-end myosin motors), or at the stereocilia tip (driven by plus-end myosin motors). The localization of proteins that influence the actin depolymerization and polymerization rates allow us to describe the narrow shape of the stereocilia base, and the observed increase of the actin polymerization rate with the stereocilia height. C1 [Naoz, Moshe; Gov, Nir S.] Weizmann Inst Sci, Dept Chem Phys, IL-76100 Rehovot, Israel. [Manor, Uri; Kachar, Bechara] Natl Inst Deafness & Other Commun Disorders, NIH, Lab Cellular Biol, Bethesda, MD USA. [Sakaguchi, Hirofumi] Kyoto Prefectural Univ Med, Dept Otolaryngol Head & Neck Surg, Kyoto, Japan. RP Gov, NS (reprint author), Weizmann Inst Sci, Dept Chem Phys, IL-76100 Rehovot, Israel. EM nir.gov@weizmann.ac.il FU Alvin and Gertrude Levine Career Development Chair; Israel Science Foundation [337/05]; National Institute on Deafness and Other Communication Disorders intramural funding FX N.S.G. thanks the Alvin and Gertrude Levine Career Development Chair, for their support. This research was supported by the Israel Science Foundation (grant No. 337/05) and by National Institute on Deafness and Other Communication Disorders intramural funding. This research is made possible in part by the historic generosity of the Harold Perlman Family. NR 47 TC 21 Z9 21 U1 0 U2 2 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD DEC 15 PY 2008 VL 95 IS 12 BP 5706 EP 5718 DI 10.1529/biophysj.108.143453 PG 13 WC Biophysics SC Biophysics GA 381TR UT WOS:000261559300017 PM 18936243 ER PT J AU Kennedy, AD Deleo, FR AF Kennedy, Adam D. Deleo, Frank R. TI PI3K and NADPH oxidase: a class act SO BLOOD LA English DT Editorial Material ID P40(PHOX); BINDING; PHAGOCYTOSIS; ACTIVATION; PHAGOSOME; DOMAIN C1 [Kennedy, Adam D.; Deleo, Frank R.] NIAID, Bethesda, MD 20892 USA. RP Kennedy, AD (reprint author), NIAID, Bethesda, MD 20892 USA. OI DeLeo, Frank/0000-0003-3150-2516 FU Intramural NIH HHS NR 8 TC 5 Z9 5 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 15 PY 2008 VL 112 IS 13 BP 4788 EP 4789 DI 10.1182/blood-2008-09-179135 PG 4 WC Hematology SC Hematology GA 381CR UT WOS:000261513400006 PM 19064736 ER PT J AU Johnson, DC Corthals, S Ramos, C Hoering, A Cocks, K Dickens, NJ Haessler, J Goldschmidt, H Child, JA Bell, SE Jackson, G Baris, D Rajkumar, SV Davies, FE Durie, BGM Crowley, J Sonneveld, P Van Ness, B Morgan, GJ AF Johnson, David C. Corthals, Sophie Ramos, Christine Hoering, Antje Cocks, Kim Dickens, Nicholas J. Haessler, Jeff Goldschmidt, Harmut Child, J. Anthony Bell, Sue E. Jackson, Graham Baris, Dalsu Rajkumar, S. Vincent Davies, Faith E. Durie, Brian G. M. Crowley, John Sonneveld, Pieter Van Ness, Brian Morgan, Gareth J. TI Genetic associations with thalidomide mediated venous thrombotic events in myeloma identified using targeted genotyping SO BLOOD LA English DT Article ID HUMAN MULTIPLE-MYELOMA; PROTHROMBOTIC COAGULATION ABNORMALITIES; DOXORUBICIN-INDUCED APOPTOSIS; PROTECTS ENDOTHELIAL-CELLS; PHASE-II TRIAL; COMBINATION THERAPY; GROWTH-FACTOR; ANGIOGENIC CYTOKINES; TISSUE FACTOR; TNF-ALPHA AB A venous thromboembolism (VTE) with the subsequent risk of pulmonary embolism is a major concern in the treatment of patients with multiple myeloma with thalidomide. The susceptibility to developing a VTE in response to thalidomide therapy is likely to be influenced by both genetic and environmental factors. To test genetic variation associated with treatment related VTE in patient peripheral blood DNA, we used a custom-built molecular inversion probe (MIP)-based single nucleotide polymorphism (SNP) chip containing 3404 SNPs. SNPs on the chip were selected in "functional regions" within 964 genes spanning 67 molecular pathways thought to be involved in the pathogenesis, treatment response, and side effects associated with myeloma therapy. Patients and controls were taken from 3 large clinical trials: Medical Research Council (MRC) Myeloma IX, Hovon-50, and Eastern Cooperative Oncology Group (ECOG) EA100, which compared conventional treatments with thalidomide in patients with myeloma. Our analysis showed that the set of SNPs associated with thalidomide-related VTE were enriched in genes and pathways important in drug transport/metabolism, DNA repair, and cytokine balance. The effects of the SNPs associated with thalidomide-related VTE may be functional at the level of the tumor cell, the tumor-related microenvironment, and the endothelium. The clinical trials described in this paper have been registered as follows: MRC Myeloma IX: ISRCTN68454111; Hovon-50: NCT00028886; and ECOG EA100: NCT00033332. (Blood. 2008;112:4924-4934) C1 [Johnson, David C.; Dickens, Nicholas J.; Davies, Faith E.; Morgan, Gareth J.] Inst Canc Res, Sect Haematooncol, London SW3 6JB, England. [Corthals, Sophie; Sonneveld, Pieter] Erasmus MC, Dept Hematol, Rotterdam, Netherlands. [Ramos, Christine; Van Ness, Brian] Univ Minnesota, Dept Genet Cell Biol & Dev, Minneapolis, MN USA. [Hoering, Antje; Haessler, Jeff; Crowley, John] Canc Res & Biostat CRAB, Seattle, WA USA. [Cocks, Kim; Child, J. Anthony; Bell, Sue E.] Univ Leeds, Clin Trials Res Unit, Leeds, W Yorkshire, England. [Goldschmidt, Harmut] Heidelberg Univ, Dept Internal Med, Amyloidosis Clin, Div Hematol Oncol, D-6900 Heidelberg, Germany. [Jackson, Graham] Newcastle Univ, Sch Lab & Clin Sci, Newcastle Upon Tyne NE1 7RU, Tyne & Wear, England. [Baris, Dalsu] NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. [Rajkumar, S. Vincent] Mayo Clin, Dept Internal Med, Div Hematol, Rochester, MN USA. [Durie, Brian G. M.] Int Myeloma Fdn, Los Angeles, CA USA. [Durie, Brian G. M.] Cedars Sinai Comprehens Canc Ctr, Los Angeles, CA USA. RP Morgan, GJ (reprint author), Inst Canc Res, Sect Haematooncol, Sutton SM2 5NG, Surrey, England. EM gareth.morgan@icr.ac.uk RI Johnson, David/A-3907-2011; OI Johnson, David/0000-0003-0887-3343; Rajkumar, S. Vincent/0000-0002-5862-1833; Dickens, Nicholas/0000-0003-0492-5855; Cocks, Kim/0000-0003-2595-708X FU International Myeloma Foundation (IMF) FX We would like to thank the staff at the Haematological Malignancy Diagnostic Service, Leeds, and members of the MRC Myeloma IX Trial Management Group, as well as consultants and patients entered in the MRC Myeloma IX, ECOG, and Hovon-50 trials.; This study was supported by the International Myeloma Foundation (IMF) as part of the Bank on a Cure (BOAC) Consortium. We are also grateful for support received from Myeloma UK. NR 93 TC 43 Z9 46 U1 0 U2 3 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 2021 L ST NW, SUITE 900, WASHINGTON, DC 20036 USA SN 0006-4971 EI 1528-0020 J9 BLOOD JI Blood PD DEC 15 PY 2008 VL 112 IS 13 BP 4924 EP 4934 DI 10.1182/blood-2008-02-140434 PG 11 WC Hematology SC Hematology GA 381CR UT WOS:000261513400023 PM 18805967 ER PT J AU Castermans, K Tabruyn, SP Zeng, R van Beijnum, JR Eppolito, C Leonard, WJ Shrikant, PA Griffioen, AW AF Castermans, Karolien Tabruyn, Sebastien P. Zeng, Rong van Beijnum, Judy R. Eppolito, Cheryl Leonard, Warren J. Shrikant, Protul A. Griffioen, Arjan W. TI Angiostatic activity of the antitumor cytokine interleukin-21 SO BLOOD LA English DT Article ID ENDOTHELIAL GROWTH-FACTOR; NATURAL-KILLER-CELLS; COMMON GAMMA-CHAIN; TUMOR ANGIOGENESIS; IL-21 RECEPTOR; IN-VIVO; INHIBITS ANGIOGENESIS; TYROSINE KINASE; GENE-EXPRESSION; NITRIC-OXIDE AB Interleukin-21 (IL-21) is a recently described immunoregulatory cytokine. It has been identified as a very potent immunotherapeutic agent in several cancer types in animal models, and clinical studies are ongoing. IL-21 belongs to the type I cytokine family of which other members, ie, IL-2, IL-15, and IL-4, have been shown to exert activities on vascular endothelial cells (ECs). We hypothesized that IL-21, in addition to inducing the antitumor immune response, also inhibits tumor angiogenesis. In vitro experiments showed a decrease of proliferation and sprouting of activated ECs after IL-21 treatment. We found that the IL-21 receptor is expressed on vascular ECs. Furthermore, in vivo studies in the chorioallantoic membrane of the chick embryo and in mouse tumors demonstrated that IL-21 treatment disturbs vessel architecture and negatively affects vessel outgrowth. Our results also confirm the earlier suggested angiostatic potential of IL-2 in vitro and in vivo. The angiostatic effect of IL-21 is confirmed by the decrease in expression of angiogenesis-related genes. Interestingly, IL-21 treatment of ECs leads to a decrease of Stat3 phosphorylation. Our research shows that IL-21 is a very powerful antitumor compound that combines the induction of an effective antitumor immune response with inhibition of tumor angiogenesis. (Blood. 2008;112: 4940-4947) C1 [Griffioen, Arjan W.] Univ Hosp Maastricht, Dept Pathol, Angiogenesis Lab, NL-6202 AZ Maastricht, Netherlands. [Castermans, Karolien; Tabruyn, Sebastien P.; van Beijnum, Judy R.; Griffioen, Arjan W.] Maastricht Univ, Sch Oncol & Dev Biol, Dept Pathol, Angiogenesis Lab, Maastricht, Netherlands. [Castermans, Karolien; Tabruyn, Sebastien P.; van Beijnum, Judy R.; Griffioen, Arjan W.] Maastricht Univ, Sch Oncol & Dev Biol, Dept Internal Med, Angiogenesis Lab, Maastricht, Netherlands. [Zeng, Rong; Leonard, Warren J.] NHLBI, Lab Mol Immunol, NIH, Bethesda, MD 20892 USA. [Eppolito, Cheryl; Shrikant, Protul A.] Roswell Pk Canc Inst, Dept Immunol, Buffalo, NY 14263 USA. RP Griffioen, AW (reprint author), Univ Hosp Maastricht, Dept Pathol, Angiogenesis Lab, POB 5800, NL-6202 AZ Maastricht, Netherlands. EM aw.griffioen@path.unimaas.nl NR 50 TC 30 Z9 31 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 15 PY 2008 VL 112 IS 13 BP 4940 EP 4947 DI 10.1182/blood-2007-09-113878 PG 8 WC Hematology SC Hematology GA 381CR UT WOS:000261513400025 PM 18515660 ER PT J AU Ahmadzadeh, M Felipe-Silva, A Heemskerk, B Powell, DJ Wunderlich, JR Merino, MJ Rosenberg, SA AF Ahmadzadeh, Mojgan Felipe-Silva, Aloisio Heemskerk, Bianca Powell, Daniel J., Jr. Wunderlich, John R. Merino, Maria J. Rosenberg, Steven A. TI FOXP3 expression accurately defines the population of intratumoral regulatory T cells that selectively accumulate in metastatic melanoma lesions SO BLOOD LA English DT Article ID TRANSCRIPTION FACTOR FOXP3; HUMAN PERIPHERAL-BLOOD; CANCER-PATIENTS; TGF-BETA; CUTTING EDGE; IN-VIVO; TUMOR; CD4(+); IL-2; LYMPHOCYTES AB Regulatory T(T(reg)) cells are often found in human tumors; however, their functional characteristics have been difficult to evaluate due to low cell numbers and the inability to adequately distinguish between activated and T(reg) cell populations. Using a novel approach, we examined the intracellular cytokine production capacity of tumor-infiltrating T cells in the single-cell suspensions of enzymatically digested tumors to differentiate T(reg) cells from effector T cells. Similar to T(reg) cells in the peripheral blood of healthy individuals, tumor-infiltrating FOXP3 + CD4 T cells, unlike FOXP3 + T cells, were unable to produce IL-2 and IFN-gamma upon ex vivo stimulation, indicating that FOXP3 expression is a valid biological marker for human T(reg) cells even in the tumor microenvironment. Accordingly, we enumerated FOXP3 + CD4 T(reg) cells in intratumoral and peritumoral sections of metastatic melanoma tumors and found a significant increase in proportion of FOXP3 + CD4 T(reg) cells in the intratumoral compared with peritumoral areas. Moreover, their frequencies were 3-to 5-fold higher in tumors than in peripheral blood from the same patients or healthy donors, respectively. These findings demonstrate that the tumor-infiltrating CD4 T(reg) cell population is accurately depicted by FOXP3 expression, they selectively accumulate in tumors, and their frequency in peripheral blood does not properly reflect tumor microenvironment. (Blood. 2008; 112: 4953-4960) C1 [Ahmadzadeh, Mojgan; Heemskerk, Bianca; Powell, Daniel J., Jr.; Wunderlich, John R.; Rosenberg, Steven A.] NCI, Surg Branch, NIH, Bethesda, MD 20892 USA. [Felipe-Silva, Aloisio; Merino, Maria J.] NCI, Pathol Lab, NIH, Bethesda, MD 20892 USA. RP Rosenberg, SA (reprint author), NCI, Surg Branch, NIH, CRC Bldg,Room 3W-3940,10 Ctr Dr, Bethesda, MD 20892 USA. EM mojgan_ahmadzadeh@nih.gov; sar@nih.gov RI Heemskerk, Bianca/C-4635-2012; FELIPE-SILVA, ALOISIO/J-9295-2012 OI FELIPE-SILVA, ALOISIO/0000-0001-6668-7907 NR 45 TC 82 Z9 87 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 15 PY 2008 VL 112 IS 13 BP 4953 EP 4960 DI 10.1182/blood-2008-06-163048 PG 8 WC Hematology SC Hematology GA 381CR UT WOS:000261513400027 PM 18820132 ER PT J AU Chu, CC Catera, R Hatzi, K Yan, XJ Zhang, L Wang, XB Fales, HM Allen, SL Kolitz, JE Rai, KR Chiorazzi, N AF Chu, Charles C. Catera, Rosa Hatzi, Katerina Yan, Xiao-Jie Zhang, Lu Wang, Xiao Bo Fales, Henry M. Allen, Steven L. Kolitz, Jonathan E. Rai, Kanti R. Chiorazzi, Nicholas TI Chronic lymphocytic leukemia antibodies with a common stereotypic rearrangement recognize nonmuscle myosin heavy chain IIA SO BLOOD LA English DT Article ID IMMUNOGLOBULIN MUTATION GENOTYPE; MEMORY B-CELLS; ANTIGEN RECEPTORS; APOPTOTIC CELLS; SOMATIC HYPERMUTATION; CARDIAC MYOSIN; T-CELLS; SELECTION; EXPRESS; AUTOANTIBODIES AB Leukemic B lymphocytes of a large group of unrelated chronic lymphocytic leukemia (CLL) patients express an unmutated heavy chain immunoglobulin variable (V) region encoded by IGHV1-69, IGHD3-16, and IGHJ3 with nearly identical heavy and light chain complementarity-determining region 3 sequences. The likelihood that these patients developed CLL clones with identical antibody V regions randomly is highly improbable and suggests selection by a common antigen. Monoclonal antibodies (mAbs) from this stereotypic subset strongly bind cytoplasmic structures in HEp-2 cells. Therefore, HEp-2 cell extracts were immunoprecipitated with recombinant stereotypic subset-specific CLL mAbs, revealing a major protein band at approximately 225 kDa that was identified by mass spectrometry as nonmuscle myosin heavy chain IIA (MYHIIA). Reactivity of the stereotypic mAbs with MYHIIA was confirmed by Western blot and immunofluorescence colocalization with anti-MYHIIA antibody. Treatments that alter MYHIIA amounts and cytoplasmic localization resulted in a corresponding change in binding to these mAbs. The appearance of MYHIIA on the surface of cells undergoing stress or apoptosis suggests that CLL mAb may generally bind molecules exposed as a consequence of these events. Binding of CLL mAb to MYHIIA could promote the development, survival, and expansion of these leukemic cells. (Blood. 2008; 112: 5122-5129) C1 [Chu, Charles C.; Catera, Rosa; Hatzi, Katerina; Yan, Xiao-Jie; Zhang, Lu; Wang, Xiao Bo; Allen, Steven L.; Kolitz, Jonathan E.; Rai, Kanti R.; Chiorazzi, Nicholas] N Shore LIJ Hlth Syst, Feinstein Inst Med Res, Manhasset, NY 11030 USA. [Chu, Charles C.; Allen, Steven L.; Kolitz, Jonathan E.; Rai, Kanti R.; Chiorazzi, Nicholas] N Shore Univ Hosp, Dept Med, Manhasset, NY USA. [Chu, Charles C.; Allen, Steven L.; Kolitz, Jonathan E.; Rai, Kanti R.; Chiorazzi, Nicholas] N Shore Univ Hosp, Dept Med, New Hyde Pk, NY USA. [Chu, Charles C.; Allen, Steven L.; Kolitz, Jonathan E.; Rai, Kanti R.; Chiorazzi, Nicholas] N Shore LIJ Hlth Syst, LIJ Med Ctr, Manhasset, NY USA. [Chu, Charles C.; Allen, Steven L.; Kolitz, Jonathan E.; Rai, Kanti R.; Chiorazzi, Nicholas] N Shore LIJ Hlth Syst, LIJ Med Ctr, New Hyde Pk, NY USA. [Chu, Charles C.; Kolitz, Jonathan E.] NYU, Dept Med, Sch Med, New York, NY 10003 USA. [Fales, Henry M.] NHLBI, Lab Appl Mass Spectrometry, NIH, Bethesda, MD 20892 USA. [Allen, Steven L.; Rai, Kanti R.; Chiorazzi, Nicholas] Albert Einstein Coll Med, Dept Med, Bronx, NY 10467 USA. [Chiorazzi, Nicholas] Albert Einstein Coll Med, Dept Cell Biol, Bronx, NY 10467 USA. RP Chu, CC (reprint author), N Shore LIJ Hlth Syst, Feinstein Inst Med Res, 350 Community Dr, Manhasset, NY 11030 USA. EM cchu@nshs.edu OI Allen, Steven/0000-0002-3482-3182 FU NIH [CA81554, CA87956, RR018535]; Karches Foundation; Peter Jay Sharp Foundation; Prince Family Foundation; Marks Foundation; Jean Walton Fund for Leukemia and Lymphoma Research; Joseph Eletto Leukemia Research Fund FX This work was supported in part by R01 grants from NIH (CA81554 and CA87956; N. C.), an M01 General Clinical Research Center grant from the NIH (RR018535; N. C.), the Intramural Research Program of NIH (H. M. F.), the Karches Foundation, the Peter Jay Sharp Foundation, the Prince Family Foundation, the Marks Foundation, the Jean Walton Fund for Leukemia and Lymphoma Research, and the Joseph Eletto Leukemia Research Fund. NR 51 TC 97 Z9 100 U1 0 U2 2 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 15 PY 2008 VL 112 IS 13 BP 5122 EP 5129 DI 10.1182/blood-2008-06-162024 PG 8 WC Hematology SC Hematology GA 381CR UT WOS:000261513400045 PM 18812466 ER PT J AU Morton, LM Wang, SS Cozen, W Linet, MS Chatterjee, N Davis, S Severson, RK Colt, JS Vasef, MA Rothman, N Blair, A Bernstein, L Cross, AJ De Roos, AJ Engels, EA Hein, DW Hill, DA Kelemen, LE Lim, UH Lynch, CF Schenk, M Wacholder, S Ward, MH Zahm, SH Chanock, SJ Cerhan, JR Hartge, P AF Morton, Lindsay M. Wang, Sophia S. Cozen, Wendy Linet, Martha S. Chatterjee, Nilanjan Davis, Scott Severson, Richard K. Colt, Joanne S. Vasef, Mohammad A. Rothman, Nathaniel Blair, Aaron Bernstein, Leslie Cross, Amanda J. De Roos, Anneclaire J. Engels, Eric A. Hein, David W. Hill, Deirdre A. Kelemen, Linda E. Lim, Unhee Lynch, Charles F. Schenk, Maryjean Wacholder, Sholom Ward, Mary H. Zahm, Shelia Hoar Chanock, Stephen J. Cerhan, James R. Hartge, Patricia TI Etiologic heterogeneity among non-Hodgkin lymphoma subtypes SO BLOOD LA English DT Article ID EPIDEMIOLOGY CONSORTIUM INTERLYMPH; ONE-CARBON METABOLISM; POOLED ANALYSIS; UNITED-STATES; RISK-FACTORS; GENETIC-VARIATION; T(14/18)-DEFINED SUBTYPES; ULTRAVIOLET-RADIATION; MALIGNANT-LYMPHOMAS; CIGARETTE-SMOKING AB Understanding patterns of etiologic commonality and heterogeneity for non-Hodgkin lymphomas may illuminate lymphomagenesis. We present the first systematic comparison of risks by lymphoma subtype for a broad range of putative risk factors in a population-based case-control study, including diffuse large B-cell (DLBCL; N = 416), follicular (N = 318), and marginal zone lymphomas (N = 106), and chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL; N = 133). We required at least 2 of 3 analyses to support differences in risk: (1) polytomous logistic regression, (2) homogeneity tests, or (3) dichotomous logistic regression, analyzing all 7 possible pairwise comparisons among the subtypes, corresponding to various groupings by clinical behavior, genetic features, and differentiation. Late birth order and high body mass index (>= 35) kg/m(2)) increased risk for DLBCL alone. Autoimmune conditions increased risk for marginal zone lymphoma alone. The tumor necrosis factor G-308A polymorphism (rs1800629) increased risks for both DLBCL and marginal zone lymphoma. Exposure to certain dietary heterocyclic amines from meat consumption increased risk for CLL/SLL alone. We observed no significant risk factors for follicular lymphoma alone. These data clearly support both etiologic commonality and heterogeneity for lymphoma subtypes, suggesting that immune dysfunction is of greater etiologic importance for DLBCL and marginal zone lymphoma than for CLL/SLL and follicular lymphoma. (Blood. 2008; 112: 5150-5160) C1 [Morton, Lindsay M.] NCI, Div Canc Epidemiol & Genet, NIH, DHHS, Rockville, MD 20852 USA. [Cozen, Wendy] Univ So Calif, Kenneth Norris Jr Comprehens Canc Ctr, Los Angeles, CA 90033 USA. [Davis, Scott; De Roos, Anneclaire J.] Fred Hutchinson Canc Res Ctr, Seattle, WA 98104 USA. [Davis, Scott; De Roos, Anneclaire J.] Univ Washington, Seattle, WA 98195 USA. [Severson, Richard K.; Schenk, Maryjean] Wayne State Univ, Dept Family Med, Detroit, MI USA. [Severson, Richard K.; Schenk, Maryjean] Wayne State Univ, Karmanos Canc Inst, Detroit, MI USA. [Vasef, Mohammad A.] Univ New Mexico, Dept Pathol, Albuquerque, NM 87131 USA. [Bernstein, Leslie] City Hope Comprehens Canc Ctr, Duarte, CA USA. [Bernstein, Leslie] City Hope Natl Med Ctr, Beckman Res Inst, Duarte, CA 91010 USA. [Hein, David W.] Univ Louisville, Sch Med, Dept Pharmacol & Toxicol, Louisville, KY 40292 USA. [Hein, David W.] Univ Louisville, Sch Med, James Graham Brown Canc Ctr, Louisville, KY 40292 USA. [Hill, Deirdre A.] Univ New Mexico, Ctr Canc, Albuquerque, NM 87131 USA. [Hill, Deirdre A.] Univ New Mexico, Dept Internal Med, Albuquerque, NM 87131 USA. [Kelemen, Linda E.; Cerhan, James R.] Mayo Clin, Coll Med, Rochester, MN USA. [Lynch, Charles F.] Univ Iowa, Dept Epidemiol, Iowa City, IA USA. [Chanock, Stephen J.] NCI, Core Genotyping Facil, Adv Technol Ctr, NIH, Gaithersburg, MD USA. RP Morton, LM (reprint author), NCI, Div Canc Epidemiol & Genet, NIH, DHHS, 6120 Execut Blvd,EPS 7040,MSC 7238, Rockville, MD 20852 USA. EM mortonli@mail.nih.gov RI Hein, David/A-9707-2008; Morton, Lindsay/B-5234-2015; OI Morton, Lindsay/0000-0001-9767-2310; Cerhan, James/0000-0002-7482-178X FU National Cancer Institute; National Institutes of Health; Public Health Service [N01-PC-65064, N01-PC-67008, N01-PC-67009, N01-PC-67010, N02-PC-71105] FX This research was supported by the Intramural Research Program of the National Cancer Institute, National Institutes of Health, and Public Health Service (contracts N01-PC-65064, N01-PC-67008, N01-PC-67009, N01-PC-67010, N02-PC-71105). NR 66 TC 101 Z9 104 U1 1 U2 14 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 15 PY 2008 VL 112 IS 13 BP 5150 EP 5160 DI 10.1182/blood-2008-01-133587 PG 11 WC Hematology SC Hematology GA 381CR UT WOS:000261513400048 PM 18796628 ER PT J AU Tamary, H Shalev, H Perez-Avraham, G Zoldan, M Levi, I Swinkels, DW Tanno, T Miller, JL AF Tamary, Hannah Shalev, Hanna Perez-Avraham, Galit Zoldan, Meira Levi, Itai Swinkels, Dorine W. Tanno, Toshihiko Miller, Jeffery L. TI Elevated growth differentiation factor 15 expression in patients with congenital dyserythropoietic anemia type I SO BLOOD LA English DT Article ID HEPCIDIN; ERYTHROPOIESIS; THALASSEMIA; CODANIN-1 AB Congenital dyserythropoietic anemia (CDA) is a rare group of red blood cell disorders characterized by ineffective erythropoiesis and increased iron absorption. To determine whether growth differentation factor 15 (GDF15) hyper-expression is associated with the ineffective erythropoiesis and iron-loading complications of CDA type I ( CDA I), GDF15 levels and other markers of erythropoiesis and iron overload were studied in blood from 17 CDA I patients. Significantly higher levels of GDF15 were detected among the CDA I patients (10 239 +/- 3049 pg/mL) compared with healthy volunteers (269 +/- 238 pg/mL). In addition, GDF15 correlated significantly with several erythropoietic and iron parameters including Hepcidin-25, Ferritin, and Hepcidin-25/Ferritin ratios. These novel results suggest that CDA I patients express very high levels of serum GDF15, and that GDF15 contributes to the inappropriate suppression of hepcidin with subsequent secondary hemochromatosis. (Blood. 2008; 112: 5241-5244) C1 [Tamary, Hannah; Zoldan, Meira] Tel Aviv Univ, Sackler Fac Med, Schneider Childrens Med Ctr Israel Petah Tikva, Hematol Oncol Ctr, IL-69978 Tel Aviv, Israel. [Shalev, Hanna; Perez-Avraham, Galit; Levi, Itai] Ben Gurion Univ Negev, Hematol Soroka Med Ctr, Fac Med, IL-84105 Beer Sheva, Israel. [Swinkels, Dorine W.] Radboud Univ Nijmegen, Dept Clin Chem, Med Ctr, NL-6525 ED Nijmegen, Netherlands. [Tanno, Toshihiko; Miller, Jeffery L.] NIDDK, Mol Med Branch, NIH, Bethesda, MD USA. RP Tamary, H (reprint author), Schneider Childrens Med Ctr Israel, Dept Pediat Hematol Oncol, IL-49202 Petah Tiqwa, Israel. EM htamary@post.tau.ac.il RI Swinkels, D.W./H-8098-2014 FU NIH; NIDDK FX This research was supported ( in part) by the Intramural Research Program of the NIH, NIDDK. NR 16 TC 69 Z9 73 U1 1 U2 2 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 15 PY 2008 VL 112 IS 13 BP 5241 EP 5244 DI 10.1182/blood-2008-06-165738 PG 4 WC Hematology SC Hematology GA 381CR UT WOS:000261513400059 PM 18824595 ER PT J AU Dores, GM Curtis, RE Toro, JR Devesa, SS Fraumeni, JF AF Dores, Graca M. Curtis, Rochelle E. Toro, Jorge R. Devesa, Susan S. Fraumeni, Joseph F., Jr. TI Incidence of Cutaneous Sebaceous Carcinoma and Risk of Associated Neoplasms Insight Into Muir-Torre Syndrome SO CANCER LA English DT Article DE sebaceous carcinoma; Muir-Torre syndrome; multiple primary cancers; skin cancer ID MALIGNANT EYELID TUMORS; MICROSATELLITE INSTABILITY; GLAND CARCINOMA; TRANSPLANT RECIPIENTS; LYNCH-SYNDROME; CANCERS; KERATOACANTHOMAS; POPULATION; FREQUENCY; PATIENT AB BACKGROUND. Sebaceous tumors of the skin occurring in association with ail internal malignancy characterize Muir-Torre syndrome (MTS), a variant of hereditary nonpolyposis colon cancer (Lynch syndrome). To the authors' knowledge, only limited information exists regarding incidence patterns of sebaceous carcinoma (SC), and no prior study has quantified risks of associated cancers. METHODS. The authors calculated cutaneous SC incidence rates (IRs) and IR ratios in 9 US Surveillance, Epidemiology, and End Results program registries (1973-2003). Indirectly standardized incidence ratios and 95% confidence intervals (95% Cls) were calculated for subsequent cancers among 2-month survivors of SC and for subsequent SC after other primary cancers. RESULTS. Among 664 cases Of cutaneous SC, nearly 90% were diagnosed among whites (IR, 0.11 per 100,000 person-years), with significantly lower IR noted among blacks (IR, 0.04). Whereas eyelid SC IRs demonstrated no sex differences and stabilized in recent years, IRs of noneyelid SC predominated in men and rose steadily over time. Survivors of SC had a 43% (95% CI, 15%-76%) increased risk of subsequent cancer, and risk of SC was elevated by 52% (95% CI, 24%-84%) among survivors of other cancers. Whether before or after SC, the significant excesses of other primary cancers were limited to noneyelid SC. Patterns suggestive of genetic predisposition included >20-fold risks for early-onset (diagnosed in patients aged <50 years) S(. associated with colon, pancreatic, ovarian, or uterine corpus cancers, whereas late-onset SC (diagnosed in patients aged >= 50 years) predisposed to Ureter cancer. CONCLUSIONS. This population-based study Of cutaneous SC revealed ail association with a spectrum of early-onset cancers consistent with NITS. Etiologic heterogeneity Was suggested by differences between eyelid and noneyelid SC in incidence patterns and associated cancer risks. Cancer 2008;113:3372-81. Published 2008 by the American Cancer Society. C1 [Dores, Graca M.] Dept Vet Affairs Med Ctr, Med Serv, Oklahoma City, OK 73104 USA. [Dores, Graca M.; Curtis, Rochelle E.; Toro, Jorge R.; Devesa, Susan S.; Fraumeni, Joseph F., Jr.] NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. RP Dores, GM (reprint author), Dept Vet Affairs Med Ctr, Med Serv 111, 921 NE 13th St, Oklahoma City, OK 73104 USA. EM doresg@mail.nih.gov FU National Cancer Institute/National Institutes of Health; Department of Veterans Affairs FX Supported by the Intramural Research Program of the National Cancer Institute/National Institutes of Health and the Department of Veterans Affairs. NR 50 TC 38 Z9 39 U1 2 U2 3 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0008-543X J9 CANCER JI Cancer PD DEC 15 PY 2008 VL 113 IS 12 BP 3372 EP 3381 DI 10.1002/cncr.23963 PG 10 WC Oncology SC Oncology GA 383HQ UT WOS:000261665100013 PM 18932259 ER PT J AU Bellizzi, KM Mustian, KM Bowen, DJ Resnick, B Miller, SM AF Bellizzi, Keith M. Mustian, Karen M. Bowen, Deborah J. Resnick, Barbara Miller, Suzanne M. TI Aging in the Context of Cancer Prevention and Control Prespectives From Behavioral Medicine SO CANCER LA English DT Editorial Material ID DECISION-MAKING; AGE; PREVALENCE; SURVIVORS; FUTURE; HEALTH C1 [Bellizzi, Keith M.] Univ Connecticut, Storrs, CT 06269 USA. [Bellizzi, Keith M.] Natl Canc Inst, Off Canc Survivorship, Bethesda, MD USA. [Mustian, Karen M.] Univ Rochester, James P Wilmot Canc Ctr, Behav Med Unit, Rochester, NY USA. [Bowen, Deborah J.] Boston Univ, Dept Social & Behav Sci, Boston, MA 02215 USA. [Resnick, Barbara] Univ Maryland, Sch Nursing, Baltimore, MD 21201 USA. [Miller, Suzanne M.] Fox Chase Canc Ctr, Behav Med Program, Philadelphia, PA 19111 USA. RP Bellizzi, KM (reprint author), Univ Connecticut, 348 Mansfield Rd,Unit 2058, Storrs, CT 06269 USA. EM keith.m.bellizzi@uconn.edu FU NCI NIH HHS [R25 CA102618, R25 CA102618-05, R01 CA104979, R01 CA104979-01A1, U10 CA037420, P30 CA006927-47S59046] NR 40 TC 3 Z9 3 U1 1 U2 2 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0008-543X J9 CANCER JI Cancer PD DEC 15 PY 2008 VL 113 IS 12 BP 3479 EP 3483 DI 10.1002/cncr.23937 PG 5 WC Oncology SC Oncology GA 384KQ UT WOS:000261744100001 PM 19058144 ER PT J AU Bellizzi, KM Mustian, KM Palesh, OG Diefenbach, M AF Bellizzi, Keith M. Mustian, Karen M. Palesh, Oxana G. Diefenbach, Michael TI Cancer Survivorship and Aging Moving the Science Forward SO CANCER LA English DT Article; Proceedings Paper CT Society-of-Behavioral-Medicine Preconference on Cancer and Aging - Challenges and Opportunities across the Cancer Control Continuum CY MAR 21, 2007 CL Washington, DC SP Soc Behav Med DE cancer survivorship; aging; elderly; quality of life; well being ID QUALITY-OF-LIFE; BREAST-CANCER; OLDER WOMEN; PHYSICAL FUNCTION; PROSTATE-CANCER; UNITED-STATES; GERIATRIC ONCOLOGY; HEALTH; AGE; CARE AB Given the high incidence and prevalence of cancer in older adults and the anticipated growth of this population over the next few decades, oncologists, geriatricians, and primary care providers will be challenged to provide timely and appropriate post-treatment care to a diverse Population of older cancer survivors. To the authors' knowledge to date, few post-treatment epidemiologic or clinical trial Studies have investigated the mental, social, and physical health issues among older cancer survivors. For this article, the authors reviewed the behavioral oncology, gerontology, geriatric, and psychology literature on cancer survivorship and aging. This report highlights several methodologic challenges that investigators face when conducting epidemiologic and cancer clinical trial research with older cancer Survivors after treatment. These challenges must be considered and overcome to develop an informative body of scientific knowledge to address the post-treatment healthcare needs of this growing population. Future research directions, new models of care, and the need for transdisciplinary approaches are discussed. Cancer 2008;113(12 suppl):3530-39. Published 2008 by the American Cancer Society. C1 [Bellizzi, Keith M.] Univ Connecticut, Storrs, CT 06269 USA. [Bellizzi, Keith M.] NCI, Off Canc Survivorship, Div Canc Control & Populat Sci, Bethesda, MD 20892 USA. [Mustian, Karen M.; Palesh, Oxana G.] Univ Rochester, James P Wilmot Canc Ctr, Behav Med Unit, Rochester, NY USA. [Diefenbach, Michael] Mt Sinai Sch Med, Oncol Serv, New York, NY USA. RP Bellizzi, KM (reprint author), Univ Connecticut, 348 Mansfield Rd,Unit 2058, Storrs, CT 06269 USA. EM Keith.M.Bellizzi@uconn.edu FU NCI NIH HHS [R25 CA102618, R25 CA102618-05, U10 CA037420] NR 89 TC 24 Z9 24 U1 7 U2 10 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0008-543X J9 CANCER JI Cancer PD DEC 15 PY 2008 VL 113 IS 12 BP 3530 EP 3539 DI 10.1002/cncr.23942 PG 10 WC Oncology SC Oncology GA 384KQ UT WOS:000261744100007 PM 19058147 ER PT J AU Harper, DP Aplan, PD AF Harper, David P. Aplan, Peter D. TI Chromosomal Rearrangements Leading to MLL Gene Fusions: Clinical and Biological Aspects SO CANCER RESEARCH LA English DT Review ID ACUTE MYELOID-LEUKEMIA; ACUTE LYMPHOBLASTIC-LEUKEMIA; HOMOLOGOUS RECOMBINATION; TOPOISOMERASE-II; INFANT-LEUKEMIA; TRANSLOCATIONS; TRANSFORMATION; PROGENITORS; CHILDREN; THERAPY AB Rearrangements of the MLL gene located at 11q23 are common chromosomal abnormalities associated with acute leukemia, especially infant and therapy-related leukemias. A variety of chimeric oncoproteins resulting from these rearrangements has been described; all of these include the NH(2)-terminal region of MLL implicated in protein-protein interactions and transcriptional repression. Although the molecular basis for the oncogenic activity of MLL chimeric proteins is incompletely understood, it seems to be derived, at least in part, through activation of clustered homeobox (HOX) genes. Here, we survey MLL gene rearrangements that are associated with acute leukemia and discuss molecular pathways leading to these rearrangements. [Cancer Res 2008;68(24):10024-7] C1 [Aplan, Peter D.] NCI, Genet Branch, NIH, Natl Naval Med Ctr,Ctr Canc Res, Bethesda, MD 20889 USA. [Harper, David P.] Uniformed Serv Univ Hlth Sci, Dept Pediat, Bethesda, MD 20814 USA. RP Aplan, PD (reprint author), NCI, Genet Branch, NIH, Natl Naval Med Ctr,Ctr Canc Res, Bldg 8,Room 5101,8901 Rockville Pike, Bethesda, MD 20889 USA. EM aplanp@mail.nih.gov RI Aplan, Peter/K-9064-2016 FU Intramural Research Program of the INK National Cancer Institute FX We apologize in advance to authors whose work we have not cited due to space limitations. We thank Michael Kuehl, Ilan Mrsch, Rolf Marschalek. Shai lzraeli, Jay Hess, Matthew Strout, Michael Caligiuri. Clara Bloomfield, Martin StanuUa. Carolyn Felix, Terrance Babbitts, Janet Rowley, Nancy Zeleznik-Le. and Michael Thirman for many thotightftil and stimulating discussions regarding MLL translocations. NR 20 TC 40 Z9 42 U1 0 U2 2 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 2008 VL 68 IS 24 BP 10024 EP 10027 DI 10.1158/0008-5472.CAN-08-2208 PG 4 WC Oncology SC Oncology GA 386FD UT WOS:000261866800003 PM 19074864 ER PT J AU Thomas, DC Baurley, JW Brown, EE Figueiredo, JC Goldstein, A Hazra, A Wilson, RT Rothman, N AF Thomas, Duncan C. Baurley, James W. Brown, Elizabeth E. Figueiredo, Jane C. Goldstein, Alisa Hazra, Aditi Wilson, Robin T. Rothman, Nathaniel TI Approaches to Complex Pathways in Molecular Epidemiology: Summary of a Special Conference of the American Association for Cancer Research SO CANCER RESEARCH LA English DT Article C1 [Thomas, Duncan C.] Univ So Calif, Dept Prevent Med, Keck Sch Med, Los Angeles, CA 90089 USA. [Brown, Elizabeth E.] Univ Alabama, Dept Epidemiol, Birmingham, AL USA. [Brown, Elizabeth E.] Univ Alabama, Dept Med & Microbiol, Birmingham, AL USA. [Goldstein, Alisa] NCI, Genet Epidemiol Branch, NIH, Rockville, MD USA. [Rothman, Nathaniel] NCI, Occupat & Environm Epidemiol Branch, Div Canc Epidemiol & Genet, NIH, Rockville, MD USA. [Hazra, Aditi] Program Mol & Genet Epidemiol, Boston, MA USA. [Hazra, Aditi] Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA. [Wilson, Robin T.] Penn State Univ, Coll Med, Hershey, PA USA. RP Thomas, DC (reprint author), Univ So Calif, Dept Prevent Med, Keck Sch Med, 1540 Alcazar St,CHP-222, Los Angeles, CA 90089 USA. EM dthomas@usc.edu; rothmann@mail.nih.gov NR 0 TC 7 Z9 8 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 J9 CANCER RES JI Cancer Res. PD DEC 15 PY 2008 VL 68 IS 24 BP 10028 EP 10030 DI 10.1158/0008-5472.CAN-08-1690 PG 3 WC Oncology SC Oncology GA 386FD UT WOS:000261866800004 PM 19074865 ER PT J AU Hillion, J Dhara, S Sumter, TF Mukherjee, M Di Cello, F Belton, A Turkson, J Jaganathan, S Cheng, LZ Ye, ZH Jove, R Aplan, P Lin, YW Wertzler, K Reeves, R Elbahlouh, O Kowalski, J Bhattacharya, R Resar, LMS AF Hillion, Joelle Dhara, Surajit Sumter, Takita Felder Mukherjee, Mita Di Cello, Francescopaolo Belton, Amy Turkson, James Jaganathan, Souyma Cheng, Linzhao Ye, Zhaohui Jove, Richard Aplan, Peter Lin, Ying-Wei Wertzler, Kelsey Reeves, Ray Elbahlouh, Ossama Kowalski, Jeanne Bhattacharya, Raka Resar, Linda M. S. TI The High-Mobility Group A1a/Signal Transducer and Activator of Transcription-3 Axis: An Achilles Heel for Hematopoietic Malignancies? SO CANCER RESEARCH LA English DT Article ID TRANSGENIC MICE; CANCER CELLS; UTERINE TUMORIGENESIS; HMGA PROTEINS; GENE; EXPRESSION; ONCOGENE; PROMOTER; BREAST; GROWTH AB 6 Although HMGA1 (high-mobility group A1; formerly HMG-I/Y) is an oncogene that is widely overexpressed in aggressive cancers, the molecular mechanisms underlying transformation by HMGA-1 are only beginning to emerge. HMGA1 encodes the HMGA1a and HMGA1b protein isoforms, which function in regulating gene expression. To determine how HMGA1 leads to neoplastic transformation, we looked for genes regulated by HMGA1 using gene expression profile analysis. Here, we show that the SIAT3 gene, which encodes the signaling molecule signal transducer and activator of transcription 3 (STAT3), is a critical downstream target of RMGA1a. SIAT3 mRNA and protein are up-regulated in fibroblasts overexpressing HMGA1a and activated STAT3 recapitulates the transforming activity of HMGA1a in fibroblasts. HMGA1a also binds directly to a conserved region of the STAT3 promoter in vivo in human leukemia cells by chromatin inummoprecipitation and activates transcription of the STAT3 promoter in transfection experiments. To determine if this pathway contributes to HMGA1-mediated transformation, we investigated STAT3 expression in our HMGA1a transgenic mice, all of which developed aggressive lymphoid malignancy. STAT3 expression was increased in the leukemia cells from our transgenics but not in control cells. Blocking STAT3 function induced apoptosis in the transgenic leukemia cells but not in controls. In primary human leukemia samples, there was a positive correlation between HMGA1a and STAT3 mRNA. Moreover, blocking STAT3 function in human leukemia or lymphoma cells led to decreased cellular motility and foci formation. Our results show that the HMGA1a-STAT3 axis is a potential Achilles heel that could be exploited therapeutically in hematopoietic and other malignancies overexpressing HMGA1a. [Cancer Res 2008:68(24):101.21-7] C1 [Hillion, Joelle; Dhara, Surajit; Sumter, Takita Felder; Mukherjee, Mita; Di Cello, Francescopaolo; Elbahlouh, Ossama; Bhattacharya, Raka; Resar, Linda M. S.] Johns Hopkins Univ, Sch Med, Div Hematol, Baltimore, MD 21205 USA. [Hillion, Joelle; Dhara, Surajit; Sumter, Takita Felder; Mukherjee, Mita; Di Cello, Francescopaolo; Belton, Amy; Elbahlouh, Ossama; Bhattacharya, Raka; Resar, Linda M. S.] Johns Hopkins Univ, Sch Med, Dept Med, Baltimore, MD 21205 USA. [Dhara, Surajit; Sumter, Takita Felder; Mukherjee, Mita; Elbahlouh, Ossama; Bhattacharya, Raka; Resar, Linda M. S.] Johns Hopkins Univ, Sch Med, Dept Pediat, Baltimore, MD 21205 USA. [Dhara, Surajit; Cheng, Linzhao; Ye, Zhaohui; Resar, Linda M. S.] Johns Hopkins Univ, Sch Med, Dept Oncol, Baltimore, MD 21205 USA. [Kowalski, Jeanne] Johns Hopkins Univ, Sch Med, Dept Biostat, Baltimore, MD 21205 USA. [Turkson, James; Jaganathan, Souyma] Univ Cent Florida, BioMol Sci Ctr, Orlando, FL 32816 USA. [Turkson, James; Jaganathan, Souyma] Univ Cent Florida, Dept Mol Biol & Microbiol, Orlando, FL 32816 USA. [Jove, Richard] City Hope Comprehens Canc Ctr, Expt Therapeut Program, Duarte, CA USA. [Jove, Richard] City Hope Natl Med Ctr, Beckman Res Inst, Div Mol Med, Duarte, CA 91010 USA. [Aplan, Peter; Lin, Ying-Wei] NCI, Ctr Canc Res, Genet Branch, Bethesda, MD 20892 USA. [Wertzler, Kelsey; Reeves, Ray] Washington State Univ, Pullman, WA 99164 USA. RP Resar, LMS (reprint author), Johns Hopkins Univ, Sch Med, Div Hematol, Ross Res Bldg,Room 1025,720 Rutland Ave, Baltimore, MD 21205 USA. EM lresar@jhmi.edu RI Aplan, Peter/K-9064-2016; OI Ye, Zhaohui/0000-0001-5272-9168 FU Intramural NIH HHS; NCI NIH HHS [R01 CA128865, P50 CA096888, P50 CA96888, R01 CA092339, R01 CA106439, R01 CA106439-04, R01 CA128865-01A1, T32 CA060441, T32 CA60441] NR 21 TC 46 Z9 46 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 2008 VL 68 IS 24 BP 10121 EP 10127 DI 10.1158/0008-5472.CAN-08-2121 PG 7 WC Oncology SC Oncology GA 386FD UT WOS:000261866800016 PM 19074878 ER PT J AU Dissanayake, SK Olkhanud, PB O'Connell, MP Carter, A French, AD Camilli, TC Emeche, CD Hewitt, KJ Rosenthal, DT Leotlela, PD Wade, MS Yang, SW Brant, L Nickoloff, BJ Messina, JL Biragyn, A Hoek, KS Taub, DD Longo, DL Sondak, VK Hewitt, SM Weeraratna, AT AF Dissanayake, Samudra K. Olkhanud, Purevdorj B. O'Connell, Michael P. Carter, Arnell French, Amanda D. Camilli, Tura C. Emeche, Chineye D. Hewitt, Kyle J. Rosenthal, Devin T. Leotlela, Poloko D. Wade, Michael S. Yang, Sherry W. Brant, Larry Nickoloff, Brian J. Messina, Jane L. Biragyn, Arya Hoek, Keith S. Taub, Dennis D. Longo, Dan L. Sondak, Vernon K. Hewitt, Stephen M. Weeraratna, Ashani T. TI Wnt5A Regulates Expression of Tumor-Associated Antigens in Melanoma via Changes in Signal Transducers and Activators of Transcription 3 Phosphorylation SO CANCER RESEARCH LA English DT Article ID PROTEIN-KINASE-C; FRIZZLED HOMOLOGS; STAT3 ACTIVATION; T-LYMPHOCYTES; CELL MOTILITY; BETA-CATENIN; CANCER; PATHWAY; METASTASIS; TRANSITION AB There are currently no effective therapies for metastatic melanoma and targeted immunotherapy results in the remission of only a very small percentage of tumors. In this study, we show that the noncanonical Wnt ligand, Wnt5A, can increase melanoma metastasis in vivo while down-regulating the expression of tumor-associated antigens important in eliciting CTL responses (e.g., MART-1, GP100, and tyrosinase). Melanosomal antigen expression is governed by MITF, PAX3, and SOX10 and is inhibited upon signal transducers and activators of transcription 3 (STAT3) activation, via decreases in PAX3 and subsequently MITF expression. Increasing Wnt5A in Wnt5A-low cells activated STAT3, and STAT3 was decreased upon Wnt5A knockdown. Downstream targets such as PAX3, MITF, and MART-1 were also affected by Wnt5A treatment or knockdown. Staining of a melanoma tissue array also highlighted the inverse relationship between MART-I and Wnt5A expression. PKC activation by phorbol ester mimicked Wnt5A effects, and Wnt5A treatment in the presence of STAT3 or PKC inhibitors did not lower MART-1 levels. CTL activation studies showed that increases in Wnt5A correspond to decreased CTL activation and vice versa, suggesting that targeting Wnt5A before immunotherapy may lead to the enhancement of current targeted immunotherapy for patients with metastatic melanoma. [Cancer Res 2008;68(24):10205-14] C1 [Dissanayake, Samudra K.; Olkhanud, Purevdorj B.; O'Connell, Michael P.; Carter, Arnell; French, Amanda D.; Camilli, Tura C.; Emeche, Chineye D.; Hewitt, Kyle J.; Rosenthal, Devin T.; Leotlela, Poloko D.; Wade, Michael S.; Yang, Sherry W.; Biragyn, Arya; Taub, Dennis D.; Longo, Dan L.; Weeraratna, Ashani T.] NIA, Immunol Lab, NIH, Gerontol Res Ctr, Baltimore, MD 21224 USA. [Brant, Larry] NIA, Res Resources Branch, NIH, Gerontol Res Ctr, Baltimore, MD 21224 USA. [Nickoloff, Brian J.] Loyola Univ, Med Ctr, Dept Pathol, Maywood, IL 60153 USA. [Messina, Jane L.; Sondak, Vernon K.] Univ S Florida, Coll Med, H Lee Moffitt Canc Ctr & Res Inst, Tampa, FL 33612 USA. [Hoek, Keith S.] Univ Zurich Hosp, Dept Dermatol, CH-8091 Zurich, Switzerland. [Hewitt, Stephen M.] NCI, Tissue Array Res Program, Pathol Lab, Ctr Canc Res,NIH, Bethesda, MD 20892 USA. RP Weeraratna, AT (reprint author), NIA, Immunol Lab, NIH, Gerontol Res Ctr, 5600 Nathan Shock Dr,Box 21, Baltimore, MD 21224 USA. EM weerarat@grc.nia.nih.gov OI Hewitt, Stephen/0000-0001-8283-1788 FU National Institute on Aging FX Intramural Research program of the National Institute on Aging. NR 38 TC 55 Z9 58 U1 0 U2 2 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 2008 VL 68 IS 24 BP 10205 EP 10214 DI 10.1158/0008-5472.CAN-08-2149 PG 10 WC Oncology SC Oncology GA 386FD UT WOS:000261866800026 PM 19074888 ER PT J AU Solomon, DA Kim, JS Cronin, JC Sibenaller, Z Ryken, T Rosenberg, SA Ressom, H Jean, W Bigner, D Yan, H Samuels, Y Waldman, T AF Solomon, David A. Kim, Jung-Sik Cronin, Julia C. Sibenaller, Zita Ryken, Timothy Rosenberg, Steven A. Ressom, Habtom Jean, Walter Bigner, Darell Yan, Hai Samuels, Yardena Waldman, Todd TI Mutational Inactivation of PTPRD in Glioblastoma Multiforme and Malignant Melanoma SO CANCER RESEARCH LA English DT Article ID PROTEIN-TYROSINE-PHOSPHATASE; TUMOR-SUPPRESSOR LOCI; COLORECTAL CANCERS; CHROMOSOME 9P; CELL-ADHESION; LUNG-CANCER; HOMOZYGOUS DELETIONS; HUMAN BREAST; SHORT ARM; GENE AB An additional tumor suppressor gene on chromosome 9p telomeric to the CDKN2A/B locus has long been postulated to exist. Using Affymetrix 250K single nucleotide polymorphism arrays to screen for copy number changes in glioblastoma multiforme (GBM), we detected a high frequency of deletions of the PTPRD gene, which encodes a receptor protein tyrosme phosphatase at chromosome 9p23-24.1. Missense and nonsense mutations of PTPRD were identified in a subset of the samples lacking deletions, including an inherited mutation with somatic loss of the wild-type allele. We then sequenced the gene in melanoma and identified 10 somatic mutations in 7 of 57 tumors (12%). Reconstitution of PTPRD expression in GBM and melanoma cells harboring deletions or mutations led to growth suppression and apoptosis that was alleviated by both the somatic and constitutional mutations. These data implicate PTPRD in the pathogenesis of tumors of neuroectodermal origin and, when taken together with other recent reports of PTPRD mutations in adenocarcinoma of the colon and lung, suggest that PTPRD may be one of a select group of tumor suppressor genes that are inactivated in a wide range of common human tumor types. (Cancer Res 2008; 68(24):10300-6] C1 [Solomon, David A.; Kim, Jung-Sik; Ressom, Habtom; Waldman, Todd] Georgetown Univ, Sch Med, Lombardi Comprehens Canc Ctr, Dept Oncol, Washington, DC 20057 USA. [Jean, Walter] Georgetown Univ, Sch Med, Dept Neurosurg, Washington, DC 20057 USA. [Cronin, Julia C.; Samuels, Yardena] NHGRI, Canc Genet Branch, NIH, Bethesda, MD 20892 USA. [Rosenberg, Steven A.] NCI, Surg Branch, NIH, Bethesda, MD 20892 USA. [Sibenaller, Zita; Ryken, Timothy] Univ Iowa, Coll Med, Dept Neurosurg, Iowa City, IA USA. [Bigner, Darell; Yan, Hai] Duke Univ, Sch Med, Dept Pathol, Preston Robert Tisch Brain Tumor Ctr, Durham, NC 27706 USA. RP Waldman, T (reprint author), Georgetown Univ, Sch Med, Lombardi Comprehens Canc Ctr, Dept Oncol, New Res Bldg E304,3970 Reservoir Rd NW, Washington, DC 20057 USA. EM waldmant@georgetown.edu FU National Cancer Institute; American Cancer Society; National Human Genuine Research Institute; The Harry J. Lloyd Charitable Trust FX T. Waldman is funded by the National Cancer Institute and the American Cancer Society. Y. Samuels is funded by the National Human Genuine Research Institute and The Harry J. Lloyd Charitable Trust. NR 29 TC 67 Z9 68 U1 0 U2 2 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 2008 VL 68 IS 24 BP 10300 EP 10306 DI 10.1158/0008-5472.CAN-08-3272 PG 7 WC Oncology SC Oncology GA 386FD UT WOS:000261866800036 PM 19074898 ER PT J AU Tuomisto, A Sund, M Tahkola, J Latvanlehto, A Savolainen, ER Autio-Harmainen, H Liakka, A Sormunen, R Vuoristo, J West, A Lahesmaa, R Morse, HC Pihlajaniemi, T AF Tuomisto, Anne Sund, Malin Tahkola, Jenni Latvanlehto, Anne Savolainen, Eeva-Riitta Autio-Harmainen, Helena Liakka, Annikki Sormunen, Raija Vuoristo, Jussi West, Anne Lahesmaa, Riitta Morse, Herbert C., III Pihlajaniemi, Taina TI A Mutant Collagen XIII Alters Intestinal Expression of Immune Response Genes and Predisposes Transgenic Mice to Develop B-Cell Lymphomas SO CANCER RESEARCH LA English DT Article ID T-CELLS; CHROMOSOMAL TRANSLOCATIONS; INHIBITORY RECEPTORS; MOLECULAR-FEATURES; CANCER; LAIR-1; DIFFERENTIATION; INFLAMMATION; LEUKEMIA; PATHOGENESIS AB Epithelial cells of mucosal surfaces are critical for maintaining immune homeostasis by aiding in the discrimination of pathogenic and commensal microorganisms and modulating the activities of antigen-presenting cells and lymphocytes. Functional breakdowns resulting in chronic infection and inflammation are associated with the development of hematologic and solid neoplasms for which detailed pathogenetic mechanisms are poorly understood. Mice heterozygous or a transgene Col13a1(del) expressing a mutant collagen XIII developed clonal mature B-cell lineage lymphomas originating in mesenteric lymph nodes (MLN). The tumors were associated with T cells and macrophages. The incidence of disease was reduced 2-fold in transgenic mice raised under specific pathogen-free conditions, suggesting a role for infectious agents. The lymphomas did not express the mutant collagen XIII, indicating that its influence on tumorigenesis was B-cell extrinsic and likely to be associated with collagen XIII-positive tissues drained by the MLN. Studies of the small intestines of transgenic mice showed that the subepithelial basement membranes (BM) were highly abnormal and that they exhibited heightened expression of genes involved in immune responses. These results define collagen XIII-dependent maintenance of the intestinal BM as a previously unappreciated component of immune responses and a critical determinant of cancer susceptibility. [Cancer Res 2008;68(24):10324-32] C1 [Tuomisto, Anne; Sund, Malin; Tahkola, Jenni; Latvanlehto, Anne; Pihlajaniemi, Taina] Univ Oulu, Bioctr, Oulu Ctr Cell Matrix Res, Dept Med Biochem & Mol Biol,Inst Biomed, FIN-90014 Oulu, Finland. [Savolainen, Eeva-Riitta] Univ Oulu, Dept Clin Chem, FIN-90014 Oulu, Finland. [Autio-Harmainen, Helena; Liakka, Annikki; Sormunen, Raija] Univ Oulu, Dept Pathol, FIN-90014 Oulu, Finland. [West, Anne; Lahesmaa, Riitta] Univ Turku, Turku Ctr Biotechnol, Turku, Finland. [West, Anne; Lahesmaa, Riitta] Abo Akad Univ, Turku, Finland. [Morse, Herbert C., III] NIAID, Immunopathol Lab, NIH, Bethesda, MD 20892 USA. RP Pihlajaniemi, T (reprint author), Univ Oulu, Bioctr, Oulu Ctr Cell Matrix Res, Dept Med Biochem & Mol Biol,Inst Biomed, FIN-90014 Oulu, Finland. EM hm16c@nih.gov; taina.pihlajaniemi@oulu.fi OI Sund, Malin/0000-0002-7516-9543; Morse, Herbert/0000-0002-9331-3705 FU Health Sciences Council of the Academy of Finland [115237, 53377]; Finnish Cancer Foundation; Sigrid Juselius Foundation; sixth EU Framework Programme [504743]; NIH; National Institute of Allergy and Infectious Diseases FX Health Sciences Council of the Academy of Finland (115237 and 53377), Finnish Cancer Foundation and Sigrid Juselius Foundation, sixth EU Framework Programme (Integrated project "Angiotargeting"; contract no. 504743) in the area of "Life sciences, genomics and biotechnology for health,'' and Intramural Research Program of the NIH, National Institute of Allergy and Infectious Diseases. NR 42 TC 7 Z9 7 U1 0 U2 2 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 J9 CANCER RES JI Cancer Res. PD DEC 15 PY 2008 VL 68 IS 24 BP 10324 EP 10332 DI 10.1158/0008-5472.CAN-08-2582 PG 9 WC Oncology SC Oncology GA 386FD UT WOS:000261866800039 PM 19074901 ER PT J AU Zhang, YJ Pastan, I AF Zhang, Yujan Pastan, Ira TI High Shed Antigen Levels within Tumors: An Additional Barrier to Immunoconjugate Therapy SO CLINICAL CANCER RESEARCH LA English DT Article ID NECROSIS-FACTOR-ALPHA; ACUTE MYELOID-LEUKEMIA; NON-HODGKINS-LYMPHOMA; SOLID TUMORS; CONVERTING-ENZYME; MONOCLONAL-ANTIBODIES; ADAM METALLOPROTEASES; SELECTIVE-INHIBITION; CHEMOTHERAPY PLUS; CIRCULATING CD20 AB Shedding of cell surface antigens is an important biological process that is used by cells to modulate responses to signals in the extracellular environment. Because antibody-based therapies of cancer target cell surface antigens, it is important to understand more about the shedding process and how it affects tumor responses to this type of therapy. Up to now most attention has been focused on measuring the concentration of shed antigens in the blood and using these to determine the presence of a tumor and as a measure of response. The recent finding that the concentration of the tumor antigen mesothelin is extremely high within the interstitial space of tumors, where it can block antibody action, and that the concentration of shed mesothelin within the tumor is lowered by chemotherapy has important implications for the successful treatment of solid tumors by immunoconjugates and whole antibodies. C1 [Zhang, Yujan; Pastan, Ira] NCI, Mol Biol Lab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. RP Pastan, I (reprint author), NCI, Mol Biol Lab, Ctr Canc Res, NIH, 37 Convent Dr,Room 5106, Bethesda, MD 20892 USA. EM pastani@mail.nih.gov FU NIH; National Cancer Institute; Center for Cancer Research FX Grant support: Intramural Research Program of the NIH, National Cancer Institute, Center for Cancer Research. NR 52 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 2008 VL 14 IS 24 BP 7981 EP 7986 DI 10.1158/1078-0432.CCR-08-0324 PG 6 WC Oncology SC Oncology GA 384ZL UT WOS:000261782600004 PM 19088013 ER PT J AU Garcia-Closas, M Chanock, S AF Garcia-Closas, Montserrat Chanock, Stephen TI Genetic Susceptibility Loci for Breast Cancer by Estrogen Receptor Status SO CLINICAL CANCER RESEARCH LA English DT Review ID GENOME-WIDE ASSOCIATION; KERATINOCYTE GROWTH-FACTOR; SINGLE-NUCLEOTIDE POLYMORPHISMS; DEL PROMOTER POLYMORPHISM; LOW-PENETRANCE BREAST; PROSTATE-CANCER; BRCA2 MUTATIONS; COMMON VARIANTS; CONFER SUSCEPTIBILITY; PROGESTERONE-RECEPTOR AB Breast cancer is a heterogeneous disease, and risk factors could be differentially associated with the development of distinct tumor subtypes that manifest different biological behavior and progression. In support of this view, there is growing evidence that known breast cancer risk factors vary by hormone receptor status and perhaps other pathologic characteristics of disease. Recent work from large consortial studies has led to the discovery of novel breast cancer susceptibility loci in genic (CASP8, FGFRZ TNRC9, MAP3K1, LSP1) and nongenic regions (8q24, 2q35, 5p12) of the genome, and to the finding of substantial heterogeneity by tumor characteristics. In particular, susceptibility loci in FGFR2, TNRC9, 8q24, 2q35, and 5p12 have stronger associations for estrogen receptor - positive (ER+) disease than estrogen receptor - negative (ER) disease. These findings suggest that common genetic variants can influence the pathologic subtype of breast cancer, and provide further support for the hypothesis that ER+ and ER- disease result from different etiologic pathways. Current studies had limited power to detect susceptibility loci for less common tumor subtypes, such as ER- disease including triple-negative and basal-like tumors. Ongoing work targeting uncommon subtypes is likely to identify additional tumor-specific susceptibility loci in the near future. Characterization of etiologic heterogeneity of breast cancer may lead to improvements in the understanding of the biological mechanisms for breast cancer, and ultimately result in improvements in prevention, early detection, and treatment. C1 [Garcia-Closas, Montserrat; Chanock, Stephen] NCI, Div Canc Epidemiol & Genet, Rockville, MD 20852 USA. RP Garcia-Closas, M (reprint author), NCI, Div Canc Epidemiol & Genet, Room 5014,6120 Execut Blvd, Rockville, MD 20852 USA. EM montse@nih.gov RI Garcia-Closas, Montserrat /F-3871-2015 OI Garcia-Closas, Montserrat /0000-0003-1033-2650 FU Intramural NIH HHS [Z99 CA999999, Z01 CP010126-12] NR 108 TC 84 Z9 85 U1 1 U2 3 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1078-0432 EI 1557-3265 J9 CLIN CANCER RES JI Clin. Cancer Res. PD DEC 15 PY 2008 VL 14 IS 24 BP 8000 EP 8009 DI 10.1158/1078-0432.CCR-08-0975 PG 10 WC Oncology SC Oncology GA 384ZL UT WOS:000261782600006 PM 19088016 ER PT J AU Amornphimoltham, P Leelahavanichkul, K Molinolo, A Patel, V Gutkind, JS AF Amornphimoltham, Panomwat Leelahavanichkul, Kantima Molinolo, Alfredo Patel, Vyomesh Gutkind, J. Silvio TI Inhibition of Mammalian Target of Rapamycin by Rapamycin Causes the Regression of Carcinogen-induced Skin Tumor Lesions SO CLINICAL CANCER RESEARCH LA English DT Article ID SQUAMOUS-CELL CARCINOMAS; MOUSE SKIN; DEPENDENT PHOSPHORYLATION; PERSISTENT ACTIVATION; NECK-CANCER; HEAD; MTOR; MODELS; RAS; IDENTIFICATION AB Purpose: The activation of Akt/mammalian target of rapamycin (mTOR) pathway represents a frequent event in squamous cell carcinoma (SCC) progression, thus raising the possibility of using specific mTOR inhibitors for the treatment of SCC patients. In this regard, blockade of mTOR with rapamycin prevents the growth of human head and neck SCC cells when xenotransplanted into immunodeficient mice. However, therapeutic responses in xenograft tumors are not always predictive of clinical anticancer activity. Experimental Design: As genetically defined and chemically induced animal cancer models often reflect better the complexity of the clinical setting, we used here a two-step chemical carcinogenesis model to explore the effectiveness of rapamycin for the treatment of skin SCC. Results: Rapamycin exerted a remarkable anticancer activity in this chemically induced cancer model, decreasing the tumor burden of mice harboring early and advanced tumor lesions, and even recurrent skin SCCs. Immunohistochemical studies on tumor biopsies and clustering analysis revealed that rapamycin causes the rapid decrease in the phosphorylation status of mTOR targets followed by the apoptotic death of cancer cells and the reduction in the growth and metabolic activity of the surviving ones, concomitant with a decrease in the population of cancer cells expressing mutant p53. This approach enabled investigating the relationship among molecular changes caused by mTOR inhibition, thus helping identify relevant biomarkers for monitoring the effectiveness of mTOR inhibition in the clinical setting. Conclusions: Together, these findings provide a strong rationale for the early evaluation of mTOR inhibitors as a molecular targeted approach to treat SCC. C1 [Amornphimoltham, Panomwat; Leelahavanichkul, Kantima; Molinolo, Alfredo; Patel, Vyomesh; Gutkind, J. Silvio] Natl Inst Dent & Craniofacial Res, Oral & Pharyngeal Canc Res, NIH, Bethesda, MD 20892 USA. RP Gutkind, JS (reprint author), Natl Inst Dent & Craniofacial Res, Oral & Pharyngeal Canc Res, NIH, 30 Convent Dr,Bldg 30,Room 212, Bethesda, MD 20892 USA. EM sg39v@nih.gov RI Gutkind, J. Silvio/A-1053-2009 FU Intramural NIH HHS [ZIA DE000558-19] NR 29 TC 39 Z9 40 U1 0 U2 7 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 2008 VL 14 IS 24 BP 8094 EP 8101 DI 10.1158/1078-0432.CCR-08-0703 PG 8 WC Oncology SC Oncology GA 384ZL UT WOS:000261782600016 PM 19073969 ER PT J AU Balleine, RL Webster, LR Davis, S Salisbury, EL Palazzo, JP Schwartz, GF Cornfield, DB Walker, RL Byth, K Clarke, CL Meltzer, PS AF Balleine, Rosemary L. Webster, Lucy R. Davis, Sean Salisbury, Elizabeth L. Palazzo, Juan P. Schwartz, Gordon F. Cornfield, Dennis B. Walker, Robert L. Byth, Karen Clarke, Christine L. Meltzer, Paul S. TI Molecular Grading of Ductal Carcinoma In situ of the Breast SO CLINICAL CANCER RESEARCH LA English DT Article ID PATHOLOGICAL PROGNOSTIC-FACTORS; GENE-EXPRESSION PROFILES; SURGICAL ADJUVANT BREAST; TERM-FOLLOW-UP; ARCHITECTURAL HETEROGENEITY; INTRADUCTAL-CARCINOMA; HISTOLOGIC GRADE; BIOLOGIC MARKERS; CANCER; CLASSIFICATION AB Purpose: Increased incidence of ductal carcinoma in situ (DCIS) associated with mammographic screening for breast cancer has emphasized the challenges of managing this condition. The aim of this study was to identify informative clinical indicators of DCIS biology by molecular profiling. Experimental Design: Areas of in situ carcinoma, atypical ductal hyperplasia, and benign epithelium were microdissected from 46 invasive breast cancers. Oligonucleotide probes showing differential expression between DCIS associated with grade 1 and 3 invasive cancer were identified by microarray-based gene expression profiling. Expression at these probes was used to define a "molecular grade" subcategorization of all samples. The genomic basis of molecular grade was examined by array-based comparative genomic hybridization. Clinical course was examined in a cohort of 134 patients with DCIS treated by surgery alone. Results: DCIS samples were designated as low or high molecular grade based on expression at 173 probes. The low molecular grade subgroup included low (n = 10) and intermediate (n = 11) nuclear grade DCIS as well as all samples of atypical ductal hyperplasia (n = 4) and benign epithelium (n = 7). The high molecular grade subgroup included DCIS of intermediate (n = 7) and high (n = 19) nuclear grade. The character and degree of genomic aberration were distinct between molecular grade subgroups. A classification tree model including nuclear grade and Ki67 score accurately predicted molecular grade for 95.7% of samples. In an independent cohort, this showed a pattern of rapid disease recurrence for high molecular grade DCIS. Conclusions: Molecular profiling indicates a binary grading scheme for DCIS. This practical approach has potential to improve clinical evaluation of DCIS. C1 [Davis, Sean; Walker, Robert L.; Meltzer, Paul S.] NCI, Genet Branch, Bethesda, MD 20892 USA. [Balleine, Rosemary L.; Webster, Lucy R.; Clarke, Christine L.] Translat Oncol Sydney W Area Hlth Serv, Sydney, NSW, Australia. [Balleine, Rosemary L.; Webster, Lucy R.; Clarke, Christine L.] Westmead Inst Canc Res, Westmead, NSW, Australia. [Balleine, Rosemary L.; Webster, Lucy R.; Byth, Karen; Clarke, Christine L.] Westmead Millennium Inst, Westmead, NSW, Australia. [Balleine, Rosemary L.; Webster, Lucy R.; Clarke, Christine L.] Univ Sydney, Sydney, NSW 2006, Australia. [Salisbury, Elizabeth L.] Inst Clin Pathol & Med Res, Westmead, NSW, Australia. [Palazzo, Juan P.] Thomas Jefferson Univ Hosp, Dept Pathol Anat & Cell Biol, Philadelphia, PA 19107 USA. [Schwartz, Gordon F.] Thomas Jefferson Univ Hosp, Dept Surg, Philadelphia, PA 19107 USA. [Cornfield, Dennis B.] Lehigh Valley Hosp, Hlth Network Labs, Dept Pathol, Allentown, PA USA. RP Meltzer, PS (reprint author), NCI, Genet Branch, 37 Convent Dr,MSC 4265,Room 6138, Bethesda, MD 20892 USA. EM pmeltzer@mail.nih.gov OI Davis, Sean/0000-0002-8991-6458 FU Cure Cancer Australia Foundation; National Health and Medical Research Council [306700]; National Breast Cancer Foundation Scholarship; Estee Lauder group of companies; The University of Sydney; The Australian Federation of University Women-South Australia Inc; Cancer Institute New South Wales Research; National Health and Medical Research Council FX Project grant support from the Cure Cancer Australia Foundation and National Health and Medical Research Council project grant 306700 (R.L. Balleine, L.R.Webster, and C.L. Clarke). L.R.Webster was recipient of a National Breast Cancer Foundation Scholarship (supported by the Estee Lauder group of companies) and travel grants from The University of Sydney (Grants-in-Aid) and The Australian Federation of University Women-South Australia Inc. Trust Fund (Jean Gilmore Bursary). She was a Cancer Institute New South Wales Research Scholar. R.L. Balleine is a Cancer Institute New South Wales Fellow, and C.L. Clarke a Principal Research Fellow of the National Health and Medical Research Council. NR 39 TC 27 Z9 30 U1 0 U2 4 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 2008 VL 14 IS 24 BP 8244 EP 8252 DI 10.1158/1078-0432.CCR-08-0939 PG 9 WC Oncology SC Oncology GA 384ZL UT WOS:000261782600034 PM 19088042 ER PT J AU Chumakov, K Ehrenfeld, E AF Chumakov, Konstantin Ehrenfeld, Ellie TI New Generation of Inactivated Poliovirus Vaccines for Universal Immunization after Eradication of Poliomyelitis SO CLINICAL INFECTIOUS DISEASES LA English DT Article ID SYNONYMOUS CODON USAGE; ATTENUATED POLIOVIRUS; PROTECTIVE PROPERTIES; SABIN STRAINS; UNITED-STATES; VIRUS; IMMUNOGENICITY; VACCINATION; CELLS; DEOPTIMIZATION AB Twenty years of global polio eradication efforts may soon eliminate the transmission of wild-type poliovirus. However, new information that has been learned about poliovirus, as well as the political realities of a modern world, demand that universal immunity against poliomyelitis be maintained, even after wild-type poliovirus is eradicated. Although 2 excellent vaccines have proven to be highly effective in the past, neither the live-attenuated vaccine nor the currently used inactivated vaccine are optimal for use in the posteradication era. Therefore, concerted efforts are urgently needed to develop a new generation of vaccine that is risk-free and affordable and can be produced on a global scale. Here, we discuss the desired properties of a vaccine and methods to create a new polio vaccine. C1 [Chumakov, Konstantin] US FDA, Off Vaccine Res & Review, Ctr Biol Evaluat & Res, Rockville, MD 20852 USA. [Ehrenfeld, Ellie] NIAID, NIH, Bethesda, MD 20892 USA. RP Chumakov, K (reprint author), US FDA, Off Vaccine Res & Review, Ctr Biol Evaluat & Res, 1401 Rockville Pike HFM-470, Rockville, MD 20852 USA. EM konstantin.chumakov@fda.hhs.gov FU National Institute of Allergy and Infectious Diseases, National Institutes of Health; US Food and Drug Administration; US Department of Health and Human Services FX National Institute of Allergy and Infectious Diseases, National Institutes of Health; US Food and Drug Administration; and US Department of Health and Human Services. NR 57 TC 29 Z9 32 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 2008 VL 47 IS 12 BP 1587 EP 1592 DI 10.1086/593310 PG 6 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 376DO UT WOS:000261163600020 PM 18990066 ER PT J AU Ramanathan, R Pau, AK Busse, KH Zemskova, M Nieman, L Kwan, R Hammer, JH Mican, JM Maldarelli, F AF Ramanathan, Roshan Pau, Alice K. Busse, Kristin H. Zemskova, Marina Nieman, Lynnette Kwan, Richard Hammer, Jean H. Mican, JoAnn M. Maldarelli, Frank TI Iatrogenic Cushing Syndrome after Epidural Triamcinolone Injections in an HIV Type 1-Infected Patient Receiving Therapy with Ritonavir-Lopinavir SO CLINICAL INFECTIOUS DISEASES LA English DT Article ID MECHANISM-BASED INHIBITION; IN-VITRO; PHARMACOKINETICS; PREDNISONE; 3A4 AB We report the first case of a human immunodeficiency virus type 1 (HIV-1)-infected individual receiving combination antiretroviral therapy, which included ritonavir, who developed Cushing syndrome with profound complications after epidural triamcinolone injections. This case highlights the potential of ritonavir interactions even with local injections of a corticosteroid. C1 [Ramanathan, Roshan] NIAID, Helminth Immunol Sect, Parasit Dis Lab, Bethesda, MD 20892 USA. [Ramanathan, Roshan] NIAID, Clin Parasitol Unit, Bethesda, MD 20892 USA. [Pau, Alice K.; Kwan, Richard; Hammer, Jean H.; Mican, JoAnn M.] NIAID, Div Clin Res, Bethesda, MD 20892 USA. [Busse, Kristin H.] Clin Pharmacokinet Res Lab, Warren G Magnuson Clin Ctr, Dept Pharm, Bethesda, MD USA. [Zemskova, Marina; Nieman, Lynnette] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Intramural Res Program Reprod & Adult Endocrinol, Bethesda, MD USA. [Maldarelli, Frank] NCI, HIV Drug Resistance Program, NIH, Bethesda, MD 20892 USA. RP Ramanathan, R (reprint author), NIAID, Helminth Immunol Sect, Parasit Dis Lab, 4 Ctr Dr,Bldg 4,Rm B1-05, Bethesda, MD 20892 USA. EM ramanathanr@niaid.nih.gov FU National Institute of Allergy and Infectious Diseases, National Cancer Institute; National Institute of Child Health and Human Development, National Institutes of Health FX National Institute of Allergy and Infectious Diseases, National Cancer Institute, and National Institute of Child Health and Human Development, National Institutes of Health. NR 12 TC 16 Z9 16 U1 0 U2 0 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 2008 VL 47 IS 12 BP E97 EP E99 DI 10.1086/593314 PG 3 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 376DO UT WOS:000261163600036 PM 18991509 ER PT J AU Trzeciak, AR Barnes, J Ejiogu, N Foster, K Brant, LJ Zonderman, AB Evans, MK AF Trzeciak, Andrzej R. Barnes, Janice Ejiogu, Ngozi Foster, Kamala Brant, Larry J. Zonderman, Alan B. Evans, Michele K. TI Age, sex, and race influence single-strand break repair capacity in a human population SO FREE RADICAL BIOLOGY AND MEDICINE LA English DT Article DE SSB repair capacity; SSB repair kinetics; DNA repair; Comet assay; gamma-irradiation; Cryopreserved lymphocytes; Oxidative DNA damage; Reference standards; Biomonitoring study; Dispersion coefficient H; Coefficient of variation ID INDUCED DNA-DAMAGE; ALKALINE COMET ASSAY; IONIZING-RADIATION; CANCER-PATIENTS; LUNG-CANCER; MOLECULAR EPIDEMIOLOGY; HEALTHY-INDIVIDUALS; HUMAN-LYMPHOCYTES; CELLS; SENSITIVITY AB Recently, we developed an improved comet assay protocol for evaluating single-strand break repair capacity (SSB-RC) in Unstimulated cryopreserved human peripheral blood mononuclear cells (PBMCs). This methodology facilitates control of interexperimental variability [A.R. Trzeciak, J. Barnes, M.K. Evans, A modified alkaline comet assay for measuring DNA repair capacity in human populations. Radiat. Res. 169 (2008) 110-121]. The fast component of SSB repair (F-SSB-RC) was assessed using a novel parameter, the initial rate of DNA repair, and the widely used half-time of DNA repair. The slow component of SSB repair (S-SSB-RC) was estimated using the residual DNA damage after 60 min. We have examined repair of gamma-radiation-induced DNA damage in PBMCs from four age-matched groups of male and female whites and African-Americans between ages 30 and 64. There is an increase in F-SSB-RC with age in white females (P<0.01) and nonsignificant decrease in F-SSB-RC in African-American females (P=0.061). F-SSB-RC is lower in white females than in white males (P<0.01). There is a decrease in F-SSB-RC with age in African-American females as compared to white females (P<0.002) and African-American males (nonsignificant, P=0.059). Age, sex, and race had a similar effect on intercellular variability of DNA damage in gamma-irradiated and repairing PBMCs. Our findings suggest that age, sex, and race influence SSB-RC as measured by the alkaline comet assay. SSB-RC may be a useful clinical biomarker. Published by Elsevier Inc. C1 [Trzeciak, Andrzej R.; Barnes, Janice; Evans, Michele K.] NIA, Cellular & Mol Biol Lab, NIH, Baltimore, MD 21224 USA. [Ejiogu, Ngozi; Foster, Kamala; Evans, Michele K.] NIA, Clin Res Branch, NIH, Baltimore, MD 21224 USA. [Brant, Larry J.; Zonderman, Alan B.] NIA, Res Resources Branch, NIH, Baltimore, MD 21224 USA. RP Evans, MK (reprint author), NIA, Cellular & Mol Biol Lab, NIH, Baltimore, MD 21224 USA. EM evansmi@grc.nia.nih.gov OI Zonderman, Alan B/0000-0002-6523-4778 FU Intramural Research Program of the NIH; National Institute on Aging FX We thank Drs. Michael J. Pazin and Patrice J. Morin for valuable discussions. We thank to Althaf Lohani for technical assistance. We also thank nurses Catherine Sackett, Mary Sam-Nwoha, and Patricia Julien-Williams who work in the HANDLS study for their careful assessment of the participants and the acquisition of clinical samples. This research was Supported by the Intramural Research Program of the NIH, National Institute on Aging. NR 42 TC 14 Z9 17 U1 0 U2 4 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0891-5849 J9 FREE RADICAL BIO MED JI Free Radic. Biol. Med. PD DEC 15 PY 2008 VL 45 IS 12 BP 1631 EP 1641 DI 10.1016/j.freeradbiomed.2008.08.031 PG 11 WC Biochemistry & Molecular Biology; Endocrinology & Metabolism SC Biochemistry & Molecular Biology; Endocrinology & Metabolism GA 384CL UT WOS:000261721800004 PM 18845243 ER PT J AU Knight, MA Hernandez, D Diede, SJ Dauwerse, HG Rafferty, I van de Leemput, J Forrest, SM Gardner, RJM Storey, E van Ommen, GJB Tapscott, SJ Fischbeck, KH Singleton, AB AF Knight, Melanie A. Hernandez, Dena Diede, Scott J. Dauwerse, Hans G. Rafferty, Ian van de Leemput, Joyce Forrest, Susan M. Gardner, R. J. McKinlay Storey, Elsdon van Ommen, Gert-Jan B. Tapscott, Stephen J. Fischbeck, Kenneth H. Singleton, Andrew B. TI A duplication at chromosome 11q12.2-11q12.3 is associated with spinocerebellar ataxia type 20 SO HUMAN MOLECULAR GENETICS LA English DT Article ID GENOMIC STRUCTURE; CDNA CLONING; GENE; LOCALIZATION; MUTATIONS; PROTEIN; DISORDERS; AMPLIFICATION; EXPRESSION; DELETION AB Spinocerebellar ataxia type 20 (SCA20) has been linked to chromosome 11q12, but the underlying genetic defect has yet to be identified. We applied single-nucleotide polymorphism genotyping to detect structural alterations in the genomic DNA of patients with SCA20. We found a 260 kb duplication within the previously linked SCA20 region, which was confirmed by quantitative polymerase chain reaction and fiber fluorescence in situ hybridization, the latter also showing its direct orientation. The duplication spans 10 known and 2 unknown genes, and is present in all affected individuals in the single reported SCA20 pedigree. While the mechanism whereby this duplication may be pathogenic remains to be established, we speculate that the critical gene within the duplicated segment may be DAGLA, the product of which is normally present at the base of Purkinje cell dendritic spines and contributes to the modulation of parallel fiber-Purkinje cell synapses. C1 [Knight, Melanie A.; Fischbeck, Kenneth H.] NINDS, Neurogenet Branch, NIH, Bethesda, MD 20892 USA. [Hernandez, Dena; Rafferty, Ian; van de Leemput, Joyce; Singleton, Andrew B.] NIA, Mol Genet Unit, NIH, Bethesda, MD 20892 USA. [Diede, Scott J.] Univ Washington, Dept Pediat, Seattle, WA 98195 USA. [Diede, Scott J.; Tapscott, Stephen J.] Fred Hutchinson Canc Res Ctr, Div Human Biol, Seattle, WA 98104 USA. [Dauwerse, Hans G.; van Ommen, Gert-Jan B.] Leiden Univ, Med Ctr, Dept Human & Clin Genet, Leiden, Netherlands. [Forrest, Susan M.] Walter & Eliza Hall Inst Med Res, Australian Genome Res Facil, Melbourne, Vic 3050, Australia. [Gardner, R. J. McKinlay; Storey, Elsdon] Genet Hlth Serv Victoria, Melbourne, Vic, Australia. [Gardner, R. J. McKinlay] Royal Childrens Hosp, Murdoch Childrens Res Inst, Melbourne, Vic, Australia. [Storey, Elsdon] Monash Univ, Dept Med Neurosci, Melbourne, Vic 3004, Australia. RP Knight, MA (reprint author), NHGRI, Med Genet Branch, Sect Mol Neurogenet, NIH, Bldg 35,Room 1A105,35 Convent Dr,MSC 3708, Bethesda, MD 20894 USA. EM knightme@mail.nih.gov RI Singleton, Andrew/C-3010-2009; Storey, Elsdon/A-9889-2013; Diede, Scott/G-2288-2012 OI Diede, Scott/0000-0001-5422-549X FU Intramural Research Programs of the National Institute on Aging [1 Z01 AG000949-02]; National Institute of Neurological Disorders and Stroke; National Institutes of Health, Department of Health and Human Services, USA; NINDS Competitive Postdoctoral Fellowship; National Institute on Aging [Z01 AG000957-05]; Pediatric Oncology Research Training Program, National Institutes of Health [2T32CA009351-29] FX The research was funded in part by the Intramural Research Programs of the National Institute on Aging ( project number 1 Z01 AG000949-02) and the National Institute of Neurological Disorders and Stroke, both of the National Institutes of Health, Department of Health and Human Services, USA. M. A. K. was supported by a NINDS Competitive Postdoctoral Fellowship. The National Institute on Aging project number associated with this work is Z01 AG000957-05. S. J. D. was supported by a Pediatric Oncology Research Training Program, National Institutes of Health 2T32CA009351-29. NR 34 TC 25 Z9 26 U1 1 U2 3 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0964-6906 J9 HUM MOL GENET JI Hum. Mol. Genet. PD DEC 15 PY 2008 VL 17 IS 24 BP 3847 EP 3853 DI 10.1093/hmg/ddn283 PG 7 WC Biochemistry & Molecular Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Genetics & Heredity GA 377VQ UT WOS:000261280300002 PM 18801880 ER PT J AU Douillard-Guilloux, G Raben, N Takikita, S Batista, L Caillaud, C Richard, E AF Douillard-Guilloux, Gaelle Raben, Nina Takikita, Shoichi Batista, Lionel Caillaud, Catherine Richard, Emmanuel TI Modulation of glycogen synthesis by RNA interference: towards a new therapeutic approach for glycogenosis type II SO HUMAN MOLECULAR GENETICS LA English DT Article ID ACID ALPHA-GLUCOSIDASE; ENZYME-REPLACEMENT THERAPY; DISEASE TYPE-II; FINE STRUCTURAL ASPECTS; POMPE-DISEASE; GAUCHER-DISEASE; MUSCLE GLYCOGEN; MOUSE MODEL; IN-VIVO; HEPATIC GLYCOGEN AB Glycogen storage disease type II (GSDII) or Pompe disease is an autosomal recessive disorder caused by defects in the acid alpha-glucosidase gene, which leads to lysosomal glycogen accumulation and enlargement of the lysosomes mainly in cardiac and muscle tissues, resulting in fatal hypertrophic cardiomyopathy and respiratory failure in the most severely affected patients. Enzyme replacement therapy has already proven to be beneficial in this disease, but correction of pathology in skeletal muscle still remains a challenge. As substrate deprivation was successfully used to improve the phenotype in other lysosomal storage disorders, we explore here a novel therapeutic approach for GSDII based on a modulation of muscle glycogen synthesis. Short hairpin ribonucleic acids (shRNAs) targeted to the two major enzymes involved in glycogen synthesis, i.e. glycogenin (shGYG) and glycogen synthase (shGYS), were selected. C2C12 cells and primary myoblasts from GSDII mice were stably transduced with lentiviral vectors expressing both the shRNAs and the enhanced green fluorescent protein (EGFP) reporter gene. Efficient and specific inhibition of GYG and GYS was associated not only with a decrease in cytoplasmic and lysosomal glycogen accumulation in transduced cells, but also with a strong reduction in the lysosomal size, as demonstrated by confocal microscopy analysis. A single intramuscular injection of recombinant AAV-1 (adeno-associated virus-1) vectors expressing shGYS into newborn GSDII mice led to a significant reduction in glycogen accumulation, demonstrating the in vivo therapeutic efficiency. These data offer new perspectives for the treatment of GSDII and could be relevant to other muscle glycogenoses. C1 [Caillaud, Catherine] Univ Paris 05, Dept Genet & Dev, Inst Cochin, CNRS,UMR 8104, F-75014 Paris, France. [Douillard-Guilloux, Gaelle; Batista, Lionel; Caillaud, Catherine; Richard, Emmanuel] INSERM, U567, Paris, France. [Raben, Nina; Takikita, Shoichi] NIH, Bethesda, MD 20892 USA. RP Caillaud, C (reprint author), Univ Paris 05, Dept Genet & Dev, Inst Cochin, CNRS,UMR 8104, 24 Rue Faubourg St Jacques, F-75014 Paris, France. EM catherine.caillaud@inserm.fr FU INSERM; Association Vaincre les Maladies Lysosomales; VML; Association Francaise contre les Myopathies; Genzyme (France); AFM FX This work was supported by INSERM and the Association Vaincre les Maladies Lysosomales (VML). E. R. was supported by post-doctoral fellowships from VML and the Association Francaise contre les Myopathies (AFM). G. D. was supported by doctoral fellowship from Genzyme (France) and AFM. NR 46 TC 19 Z9 19 U1 0 U2 2 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0964-6906 J9 HUM MOL GENET JI Hum. Mol. Genet. PD DEC 15 PY 2008 VL 17 IS 24 BP 3876 EP 3886 DI 10.1093/hmg/ddn290 PG 11 WC Biochemistry & Molecular Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Genetics & Heredity GA 377VQ UT WOS:000261280300005 PM 18782850 ER PT J AU Raben, N Hill, V Shea, L Takikita, S Baum, R Mizushima, N Ralston, E Plotz, P AF Raben, Nina Hill, Victoria Shea, Lauren Takikita, Shoichi Baum, Rebecca Mizushima, Noboru Ralston, Evelyn Plotz, Paul TI Suppression of autophagy in skeletal muscle uncovers the accumulation of ubiquitinated proteins and their potential role in muscle damage in Pompe disease SO HUMAN MOLECULAR GENETICS LA English DT Article ID ACID ALPHA-GLUCOSIDASE; ENZYME REPLACEMENT THERAPY; GLYCOGEN AUTOPHAGY; STORAGE-DISEASE; GENE-EXPRESSION; SELF-DIGESTION; NEWBORN RATS; MOUSE MODEL; CELL-DEATH; MICE AB The role of autophagy, a catabolic lysosome-dependent pathway, has recently been recognized in a variety of disorders, including Pompe disease, the genetic deficiency of the glycogen-degrading lysosomal enzyme acid-alpha glucosidase. Accumulation of lysosomal glycogen, presumably transported from the cytoplasm by the autophagic pathway, occurs in multiple tissues, but pathology is most severe in skeletal and cardiac muscle. Skeletal muscle pathology also involves massive autophagic buildup in the core of myofibers. To determine if glycogen reaches the lysosome via autophagy and to ascertain whether autophagic buildup in Pompe disease is a consequence of induction of autophagy and/or reduced turnover due to defective fusion with lysosomes, we generated muscle-specific autophagy-deficient Pompe mice. We have demonstrated that autophagy is not required for glycogen transport to lysosomes in skeletal muscle. We have also found that Pompe disease involves induction of autophagy but manifests as a functional deficiency of autophagy because of impaired autophagosomal-lysosomal fusion. As a result, autophagic substrates, including potentially toxic aggregate-prone ubiquitinated proteins, accumulate in Pompe myofibers and may cause profound muscle damage. C1 [Raben, Nina; Hill, Victoria; Shea, Lauren; Takikita, Shoichi; Baum, Rebecca; Plotz, Paul] NIAMSD, Arthrit & Rheumatism Branch, NIH, Bethesda, MD 20892 USA. [Ralston, Evelyn] NIAMSD, Light Imaging Sect, Off Sci & Technol, NIH, Bethesda, MD 20892 USA. [Mizushima, Noboru] Tokyo Med & Dent Univ, Dept Physiol & Cell Biol, Tokyo, Japan. RP Raben, N (reprint author), NIAMS, NIH, 50 S Dr,Bld 50-1345, Bethesda, MD 20892 USA. EM rabenn@arb.niams.nih.gov RI Mizushima, Noboru/C-3635-2009 OI Mizushima, Noboru/0000-0002-6258-6444 FU National Institutes of Health; CRADA; Genzyme Corporation (Framingham, MA) FX This research was supported by the Intramural Research Program of the National Institute of Arthritis and Musculoskeletal and Skin Diseases of the National Institutes of Health. S. T. was supported in part by a CRADA between the NIH and Genzyme Corporation (Framingham, MA). NR 60 TC 141 Z9 146 U1 1 U2 8 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0964-6906 J9 HUM MOL GENET JI Hum. Mol. Genet. PD DEC 15 PY 2008 VL 17 IS 24 BP 3897 EP 3908 DI 10.1093/hmg/ddn292 PG 12 WC Biochemistry & Molecular Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Genetics & Heredity GA 377VQ UT WOS:000261280300007 PM 18782848 ER PT J AU Domene, S Roessler, E El-Jaick, KB Snir, M Brown, JL Velez, JI Bale, S Lacbawan, F Muenke, M Feldman, B AF Domene, Sabina Roessler, Erich El-Jaick, Kenia B. Snir, Mirit Brown, Jamie L. Velez, Jorge I. Bale, Sherri Lacbawan, Felicitas Muenke, Maximilian Feldman, Benjamin TI Mutations in the human SIX3 gene in holoprosencephaly are loss of function SO HUMAN MOLECULAR GENETICS LA English DT Article ID EYE DEVELOPMENT; FOREBRAIN DEVELOPMENT; MOLECULAR NATURE; NEURAL PLATE; SINE-OCULIS; ZEBRAFISH; EXPRESSION; WNT; REPRESSOR; FAMILY AB Holoprosencephaly (HPE) is the most common developmental anomaly of the human forebrain; however, the genetics of this heterogeneous and etiologically complex malformation is incompletely understood. Heterozygous mutations in SIX3, a transcription factor gene expressed in the anterior forebrain and eyes during early vertebrate development, have been frequently detected in human HPE cases. However, only a few mutations have been investigated with limited functional studies that would confirm a role in HPE pathogenesis. Here, we report the development of a set of robust and sensitive assays of human SIX3 function in zebrafish and apply these to the analysis of a total of 46 distinct mutations (19 previously published and 27 novel) located throughout the entire SIX3 gene. We can now confirm that 89% of these putative deleterious mutations are significant loss-of-function alleles. Since disease-associated single point mutations in the Groucho-binding eh1-like motif decreases the function in all assays, we can also confirm that this interaction is essential for human SIX3 co-repressor activity; we infer, in turn, that this function is important in HPE causation. We also unexpectedly detected truncated versions with partial function, yet missing a SIX3-encoded homeodomain. Our data indicate that SIX3 is a frequent target in the pathogenesis of HPE and demonstrate how this can inform the genetic counseling of families. C1 [Feldman, Benjamin] NHGRI, Med Genet Branch, NIH, Bethesda, MD 20892 USA. [Bale, Sherri] GeneDx, Gaithersburg, MD 20877 USA. RP Feldman, B (reprint author), NHGRI, Med Genet Branch, NIH, 35 Convent Dr,MSC 3717 Bldg 35,Room 1B-205, Bethesda, MD 20892 USA. EM bfeldman@mail.nih.gov OI Feldman, Benjamin/0000-0003-4838-8641 FU Division of Intramural Research; NHGRI; NIH, USA FX This work was supported in part by the Division of Intramural Research, NHGRI, NIH, USA. NR 43 TC 29 Z9 30 U1 0 U2 2 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0964-6906 J9 HUM MOL GENET JI Hum. Mol. Genet. PD DEC 15 PY 2008 VL 17 IS 24 BP 3919 EP 3928 DI 10.1093/hmg/ddn294 PG 10 WC Biochemistry & Molecular Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Genetics & Heredity GA 377VQ UT WOS:000261280300009 PM 18791198 ER PT J AU Zhu, H Glasgow, W George, MD Chrysovergis, K Olden, K Roberts, JD Eling, T AF Zhu, Hong Glasgow, Wayne George, Margaret D. Chrysovergis, Kali Olden, Kenneth Roberts, John D. Eling, Thomas TI 15-Lipoxygenase-1 activates tumor suppressor p53 independent of enzymatic activity SO INTERNATIONAL JOURNAL OF CANCER LA English DT Article DE 15-lipoxygenase-1; the tumor suppressor p53; DNA-dependent protein kinase; p53 phosphorylation; HCT-116 cells ID COLORECTAL-CANCER CELLS; DAMAGE-INDUCED PHOSPHORYLATION; DEPENDENT PROTEIN-KINASE; CARCINOMA CACO-2 CELLS; DRUG-INDUCED APOPTOSIS; DOWN-REGULATION; EXPRESSION; 12-LIPOXYGENASE; OVEREXPRESSION; IDENTIFICATION AB 15-LOX-1 and its metabolites are involved in colorectal cancer. Recently, we reported that 15-LOX-1 overexpression in HCT-116 human colorectal cancer cells inhibited cell growth by induction of p53 phosphorylation (4). To determine whether the 15-LOX-1 protein or its metabolites are responsible for phosphorylation of p53 in HCT-116 cells, we used HCT-116 cells that expressed a mutant 15-LOX-1. The mutant 15-LOX-1 enzyme, with a substitution of Leu at residue His361, was devoid of enzymatic activity. HCT-116 cells transiently transfected with either native or mutant 15-LOX-1 showed an increase in p53 phosphorylation and an increase in the expression of downstream genes. Thus, 15-LOX-1 induces p53 phosphorylation independent of enzymatic activity. Treatment of A549 human lung carcinoma cells with IL-4 increased the expression of 15-LOX-1 and also increased the expression of downstream targets of p53. This confirmed that the activation of p53 was also observed in wild-type cells expressing physiological 15-LOX-1. Immunoprecipitation experiments revealed that 15-LOX-1 interacts with, and binds to, DNA-dependent protein kinase (DNA-PK). The binding of 15-LOX-1 to DNA-PK caused an approximate 3.0-fold enhancement in kinase activity, resulting in increased p53 phosphorylation at Ser15. Knockdown of DNA-PK by small interfering RN A (siRNA) significantly reduced p53 phosphorylation. Furthermore, confocal microscopy demonstrated a colocalization of 15-LOX and DNA-PK in the cells. We propose that the 15-LOX-1 protein binds to DNA-PK, increasing its kinase activity and results in downstream activation of the tumor suppressor p53, thus revealing a new mechanism by which lipoxygenases (LOX) may influence the phenotype of tumor cells. Published 2008 Wiley-Liss, Inc. C1 [Zhu, Hong; Chrysovergis, Kali; Eling, Thomas] NIEHS, Mol Carcinogenesis Lab, NIH, Eicosanoid Biochem Sect,DHHS, Res Triangle Pk, NC 27709 USA. [Glasgow, Wayne] Mercer Univ, Sch Med, Macon, GA 31207 USA. [George, Margaret D.; Olden, Kenneth; Roberts, John D.] NIEHS, Metastasis Sect, Mol Carcinogenesis Lab, NIH,DHHS, Res Triangle Pk, NC USA. RP Eling, T (reprint author), NIEHS, Mol Carcinogenesis Lab, NIH, Eicosanoid Biochem Sect,DHHS, MD E4-09,111 TW Alexander Driver, Res Triangle Pk, NC 27709 USA. EM eling@niehs.nih.gov FU National Institute of Environmental Health Sciences, NIH (Intramural Research Program) FX Grant sponsor: National Institute of Environmental Health Sciences, NIH (Intramural Research Program). NR 42 TC 9 Z9 10 U1 0 U2 0 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0020-7136 J9 INT J CANCER JI Int. J. Cancer PD DEC 15 PY 2008 VL 123 IS 12 BP 2741 EP 2749 DI 10.1002/ijc.23855 PG 9 WC Oncology SC Oncology GA 375KO UT WOS:000261112900003 PM 18785202 ER PT J AU Bluhm, E McNeil, DE Cnattingius, S Gridley, G El Ghormli, L Fraumeni, JF AF Bluhm, Elizabeth McNeil, Dawn Elizabeth Cnattingius, Sven Gridley, Gloria El ghormli, Laure Fraumeni, Joseph F., Jr. TI Prenatal and perinatal risk factors for neuroblastoma SO INTERNATIONAL JOURNAL OF CANCER LA English DT Article DE neuroblastoma; prenatal; delayed effects; prenatal exposure; anemia; case-control study ID CHILDHOOD-CANCER; NEURO-BLASTOMA; BIRTH CHARACTERISTICS; MEDICATION USE; CONGENITAL-ANOMALIES; YOUNG-CHILDREN; BRAIN-TUMORS; PREGNANCY; ASSOCIATION; DEFECTS AB Neuroblastoma is a rare embryonal tumor of childhood for which risk factors are not well known. Using a nested case-control design, we investigated prenatal, perinatal and neonatal risk factors in detail by linking 245 pediatric neuroblastoma cases identified in the Swedish Cancer Register diagnosed in the year 1973-1995 with the Swedish Medical Birth Register. Five living controls per case were randomly selected from the birth registry, matched by gender and age. Increased risks were associated with maternal anemia during pregnancy (odds ratio (OR) = 2.95, 95% confidence interval (CI): 1.53, 5.69), neonatal respiratory distress (OR = 3.61, 95% CI: 1.41, 9.24) and low (below or equal to 7) 1-min Apgar score (OR = 2.23, 95% CI: 1.41, 3.52). Increased risks were limited to cases diagnosed before 1 year of age. Markers of prenatal, perinatal and neonatal distress may be associated with neuroblastoma in infancy, but not with diagnoses at 1 year or above. Published 2008 Wiley-Liss, Inc. C1 [Bluhm, Elizabeth] Washington Hosp Ctr, Gen Internal Med Sect, Washington, DC 20010 USA. [Bluhm, Elizabeth] NCI, Radiat Epidemiol Branch, Div Canc Epidemiol & Genet, NIH, Bethesda, MD 20892 USA. [McNeil, Dawn Elizabeth] US FDA, Div Neurol Drug Prod, Silver Spring, MD USA. [Cnattingius, Sven] Karolinska Inst, Dept Med Epidemiol & Biostat, Stockholm, Sweden. [Gridley, Gloria] NCI, Biostat Branch, Div Canc Epidemiol & Genet, NIH, Bethesda, MD 20892 USA. [El ghormli, Laure] George Washington Univ, Ctr Biostat, Rockville, MD USA. [Fraumeni, Joseph F., Jr.] NCI, Div Canc Epidemiol & Genet, NIH, Bethesda, MD 20892 USA. RP Bluhm, E (reprint author), Washington Hosp Ctr, Gen Internal Med Sect, POB 1A-50,110 Irving St NW, Washington, DC 20010 USA. EM elizabeth.c.bluhm@medstar.net FU Intramural Research Program of the NIH, National Cancer Institute, Division of Cancer Epidemiology and Genetics FX Grant sponsor: Intramural Research Program of the NIH, National Cancer Institute, Division of Cancer Epidemiology and Genetics. NR 53 TC 14 Z9 14 U1 1 U2 5 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0020-7136 J9 INT J CANCER JI Int. J. Cancer PD DEC 15 PY 2008 VL 123 IS 12 BP 2885 EP 2890 DI 10.1002/ijc.23847 PG 6 WC Oncology SC Oncology GA 375KO UT WOS:000261112900021 PM 18798548 ER PT J AU Mirochnick, M Best, BM Stek, AM Capparelli, E Hu, CC Burchett, SK Holland, DT Smith, E Gaddipati, S Read, JS AF Mirochnick, Mark Best, Brookie M. Stek, Alice M. Capparelli, Edmund Hu, Chengcheng Burchett, Sandra K. Holland, Diane T. Smith, Elizabeth Gaddipati, Sreedhar Read, Jennifer S. CA PACTG 1026s Study Team TI Lopinavir Exposure With an Increased Dose During Pregnancy SO JAIDS-JOURNAL OF ACQUIRED IMMUNE DEFICIENCY SYNDROMES LA English DT Article DE HIV; lopinavir; mother-to-child transmission; pharmacokinetics; pregnancy ID INHIBITOR-EXPERIENCED PATIENTS; RITONAVIR; ANTIRETROVIRALS; WOMEN AB Background: Use of standard adult lopinavir/ritonavir (LPV/RTV) closing (400/100 mg) during the third trimester of pregnancy results in reduced LPV exposure. The goal of this study was to determine LPV exposure during the third trimester of pregnancy and 2 weeks postpartum with a higher LPV/RTV dose. Methods: The Pediatric AIDS Clinical Trials Group protocol 1026s is all ongoing, prospective, nonblinded study of antiretroviral pharmacokinetics in HIV-infected pregnant women that included a cohort receiving LPV/RTV 400/100 mg twice daily during the second trimester and 533/133 mg twice daily during the third trimester through 2 weeks postpartum. Intensive steady state 12-hour pharmacokinetic profiles were performed during the third trimester and at 2 weeks postpartum and were optional during the second trimester. LPV and RTV were measured by reverse-phase high-performance liquid chromatography with a detection limit of 0.09 mu g/mL. Results: Twenty-six HIV-infected pregnant women were studied. Median LPV area under the plasma concentration-time curve (AUCs) for the second trimester, third trimester, and postpartum were 57, 88, and 152 respectively. Median minimum LPV concentrations were 1.9, 4.1, and 8.3 mu g/mL. Conclusions: The higher LPV/RTV dose (533/133 mg) provided LPV exposure during the third trimester similar to the median AUC (80 mu g.h(-1).mL(-1)) in nonpregnant adults taking standard doses. However, the AUC on this increased dose at 2 weeks postpartum was considerably higher. These data Suggest that the higher LPV/RTV dose should be used in third trimester pregnant women; that it should be considered in second trimester pregnant women, especially those who are protease inhibitor experienced; and that postpartum LPV/RTV dosing can be reduced to standard closing by 2 weeks after delivery. C1 [Mirochnick, Mark] Boston Univ, Sch Med, Dept Pediat, Boston, MA 02118 USA. [Best, Brookie M.; Capparelli, Edmund; Holland, Diane T.] Univ Calif San Diego, Sch Med, San Diego, CA 92103 USA. [Best, Brookie M.; Capparelli, Edmund; Holland, Diane T.] Univ Calif San Diego, Sch Pharm, San Diego, CA USA. [Best, Brookie M.; Capparelli, Edmund; Holland, Diane T.] Univ Calif San Diego, Sch Pharmaceut Sci, San Diego, CA USA. [Stek, Alice M.] Univ So Calif, Sch Med, Dept Obstet & Gynecol, Los Angeles, CA 90033 USA. [Hu, Chengcheng] Harvard Univ, Sch Publ Hlth, Stat & Data Anal Ctr, Boston, MA 02115 USA. [Burchett, Sandra K.] Childrens Hosp, Div Infect Dis, Boston, MA 02115 USA. [Smith, Elizabeth] NIAID, Bethesda, MD 20892 USA. [Gaddipati, Sreedhar] Columbia Univ Coll Phys & Surg, Dept Obstet & Gynecol, New York, NY 10032 USA. [Read, Jennifer S.] NICHHD, Pediat Adolescent & Maternal AIDS Branch, NIH, Dept Hlth & Human Serv, Bethesda, MD 20892 USA. RP Mirochnick, M (reprint author), Boston Med Ctr, Yawkey 2N-06, Boston, MA 02118 USA. EM markm@bu.edu RI Hu, Chengcheng/A-8391-2017 FU Pediatric AIDS Clinical Trials Group; National Institute of Allergy and Infections Diseases [U01 A104189, U01 A141089, UOI A127560-18, U01 AI32907]; General Clinical Research Center Units; National Center for Research Resources [MOI RR00069, M01 RR00533, M01 RR01271]; Pediatric/Perinatal HIV Clinical Trials Network; National Institute of Child Health and Human Development [N01-HD-3-3365] FX Supported in part by the Pediatric AIDS Clinical Trials Group of the National Institute of Allergy and Infections Diseases (Grants U01 A104189, U01 A141089, UOI A127560-18, and U01 AI32907), the General Clinical Research Center Units funded by the National Center for Research Resources (Grants MOI RR00069, M01 RR00533, and M01 RR01271), and by the Pediatric/Perinatal HIV Clinical Trials Network of the National Institute of Child Health and Human Development (Contract N01-HD-3-3365). NR 18 TC 46 Z9 46 U1 0 U2 0 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 2008 VL 49 IS 5 BP 485 EP 491 DI 10.1097/QAI.0b013e318186edd0 PG 7 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA 376YN UT WOS:000261219000004 PM 18989231 ER PT J AU Robertson, SM Maldarelli, F Natarajan, V Formentini, E Alfaro, RM Penzak, SR AF Robertson, Sarah M. Maldarelli, Frank Natarajan, Ven Formentini, Elizabeth Alfaro, Raul M. Penzak, Scott R. TI Efavirenz Induces CYP2B6-Mediated Hydroxylation of Bupropion in Healthy Subjects SO JAIDS-JOURNAL OF ACQUIRED IMMUNE DEFICIENCY SYNDROMES LA English DT Article DE efavirenz; bupropion; metabolism; CYP2B6; drug interaction; induction ID CYTOCHROME P4502B6 ACTIVITY; POTENTIAL-DRUG INTERACTIONS; IN-VITRO; HUMAN LIVER; POPULATION PHARMACOKINETICS; CATALYTIC-ACTIVITY; CYP2B6; METABOLISM; POLYMORPHISM; SUBSTRATE AB Objective: To characterize the effect of efavirenz on bupropion hydroxylation as a marker of cytochrome P450 (CYP) 2136 activity in healthy subjects. Methods: Thirteen subjects received a single oral dose of bupropion SR 150 mg before and after 2 weeks of efavirenz administration for comparison of bupropion and hydroxybupropion pharmacokinetics. Efavirenz plasma concentrations were also assessed. Subjects were genotyped for CYP2B6 (G516T, C1459T, and A785G), CYP3A4 (A-392G), CYP3A5 (A6986G), and multidrug resistance protein 1 (C3435T). Results: The area under the concentration vs. time curve ratio of hydroxybupropion: bupropion increased 2.3-fold after efavirenz administration (P = 0.0001). Bupropion area under the concentration vs. time curve and C(max) decreased by 55% and 34%, respectively (P < 0.002). None of the CYP2B6 or CYP3A genotypes evaluated were associated with a difference in bupropion or efavirenz clearance. The 2 individuals homozygous for multidrug resistance protein 1 3435-T/T had 2.5- and 1.8-fold greater bupropion and efavirenz clearance, respectively, relative to C/C and C/T individuals (P < 0.05). Conclusions: Our results confirm that efavirenz induces CYP2B6 enzyme activity in vivo, as demonstrated by an increase in bupropion hydroxylation after 2 weeks of efavirenz administration. C1 [Robertson, Sarah M.] US FDA, Off Clin Pharmacol, Ctr Drug Evaluat & Res, Silver Spring, MD 20993 USA. [Maldarelli, Frank] Natl Canc Inst, HIV Drug Resistance Program, Frederick, MD USA. [Natarajan, Ven] Natl Canc Inst, SAIC Frederick, Mol Cell Biol Lab, Frederick, MD USA. [Formentini, Elizabeth] NIH, Dept Crit Care Med, Bethesda, MD 20892 USA. [Alfaro, Raul M.; Penzak, Scott R.] NIH, Clin Res Ctr, Dept Pharm, Bethesda, MD 20892 USA. RP Robertson, SM (reprint author), US FDA, Off Clin Pharmacol, Ctr Drug Evaluat & Res, Bldg 21,Room 4653,10903 New Hampshire Ave, Silver Spring, MD 20993 USA. EM sarah.robertson@fda.hhs.gov FU Society of Infectious Diseases Pharmacists/Pfizer Award; Research in Infectious Disease Phamacotherapy FX Supported by the Society of Infectious Diseases Pharmacists/Pfizer Award for Research in Infectious Disease Phamacotherapy; awarded December 2005. NR 39 TC 37 Z9 37 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 2008 VL 49 IS 5 BP 513 EP 519 DI 10.1097/QAI.0b013e318183a425 PG 7 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA 376YN UT WOS:000261219000008 PM 18989234 ER PT J AU Guanira, JV Casper, C Lama, JR Morrow, R Montano, SM Caballero, P Suarez, L Whittington, WLH Wald, A Sanchez, J Celum, C AF Guanira, Juan V. Casper, Corey Lama, Javier R. Morrow, Rhoda Montano, Silvia M. Caballero, Patricia Suarez, Luis Whittington, William L. H. Wald, Anna Sanchez, Jorge Celum, Connie CA Peruvian HIV Sentinel Surveillance TI Prevalence and Correlates of Human Herpesvirus 8 Infection Among Peruvian Men Who Have Sex With Men SO JAIDS-JOURNAL OF ACQUIRED IMMUNE DEFICIENCY SYNDROMES LA English DT Article DE human herpesvirus 8; homosexual men; HIV; Peru; sexually transmitted infections ID KAPOSIS-SARCOMA; TESTING STRATEGY; BLOOD-DONORS; RISK-FACTORS; HIV; ANTIBODIES; SEROPREVALENCE; POPULATIONS; BRAZIL; HHV-8 AB Background: Infection with human herpesvirus 8 (HHV-8) is common among men who have sex with men (MSM) in North America and Europe and is also found to be endemic in some regions Of South America. Little is known about HHV-8 prevalence and its correlates among MSM in the Andean region. Methods: We assessed HHV-8 seroprevalence among 497 MSM recruited for the 2002 Peruvian HIV sentinel surveillance program using a combined HHV-8 enzyme immunoassay and immunofluorescence assay algorithm. Logistic regression analysis was used to estimate odds ratios (ORs) and their 95% confidence intervals (CIs) to determine the association between selected covariates and HHV-8 scropositivity. Results: One hundred thirty-one (66.5%, 95% CI 63.1%, to 69.9%) of 197 HIV-infected and 80 (26.7%, 95% CI 24.4% to 29.0%) of 300 HIV-uninfected MSM had serologic evidence of HHV-8 infection. Factors independently associated with HHV-8 infection were education < 12 years (OR 1.7, 95%) CI 1.1 to 2.7), anal receptive sex with the last partner (OR 2.0, 95% CI 1.2 to 3.3), self-reported sexually transmitted infection symptoms during the last year (OR 1.9, 95% CI 1.2 to 3.0), coinfection with HIV (OR 4.2, 95%, CI 2.8 to 6.4) and chronic hepatitis B (OR 4.9, 95% CI 1.5 to 15.8). MSM with long-standing HIV infection were more likely to have serologic evidence of HHV-8 infection when compared with men with recently acquired HIV (OR 3.8, 95% CI 1.7 to 9.1). Conclusions: HHV-8 infection is common among both HIV-infected and HIV-negative MSM in Lima, Peru. HHV-8 scropositivity is correlated with anal receptive sex, self-reported sexually transmitted infection symptoms, and HIV infection among these MSM and thus seems to be sexually transmitted. HHV-8 infection seems to be acquired after HIV infection, Suggesting that future studies should evaluate the mode of HHV-8 transmission and prevention strategies among HIV-uninfected MSM. C1 [Guanira, Juan V.; Lama, Javier R.; Sanchez, Jorge] Invest Med Salud INMENSA, Lima 14, Peru. [Casper, Corey; Whittington, William L. H.; Wald, Anna; Celum, Connie] Univ Washington, Dept Med, Seattle, WA USA. [Casper, Corey; Wald, Anna; Celum, Connie] Univ Washington, Dept Epidemiol, Seattle, WA 98195 USA. [Casper, Corey] Fred Hutchinson Canc Res Ctr, Vaccine & Infect Dis Inst, Seattle, WA USA. [Morrow, Rhoda; Wald, Anna] Univ Washington, Dept Lab Med, Seattle, WA 98195 USA. [Morrow, Rhoda] Childrens Hosp & Reg Med Ctr, Seattle, WA USA. [Montano, Silvia M.] US Naval Med Res Ctr Detachment, Virol Program, Lima, Peru. [Suarez, Luis] Minist Hlth Peru, Gen Directorate Epidemiol, Lima, Peru. [Caballero, Patricia] NIH, Bethesda, MD 20892 USA. [Celum, Connie] Univ Washington, Dept Global Hlth, Seattle, WA USA. RP Guanira, JV (reprint author), Invest Med Salud INMENSA, Jose De La Torre Ugarte 166, Lima 14, Peru. EM jguanira@inmensa.org RI Wald, Anna/B-6272-2012; Valle, Ruben/A-7512-2013; OI Wald, Anna/0000-0003-3486-6438; Guanira, Juan/0000-0002-2746-3086 FU The Fogarty International Center; University of Washington International AIDS Research and Training Program; US National Institute of Health Research [D43 TW000007]; 9th International Conference in Malignancies [62787A S17 H B0002] FX Supported by funds of The Fogarty International Center through the University of Washington International AIDS Research and Training Program and US National Institute of Health Research, Grant no D43 TW000007 and Work Unit number 62787A S17 H B0002. Presented in part at the 9th International Conference in Malignancies NR 22 TC 7 Z9 7 U1 0 U2 2 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 2008 VL 49 IS 5 BP 557 EP 562 DI 10.1097/QAI.0b013e31818d5bf8 PG 6 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA 376YN UT WOS:000261219000015 PM 18989224 ER PT J AU Gardel, ML Sabass, B Ji, L Danuser, G Schwarz, US Waterman, CM AF Gardel, Margaret L. Sabass, Benedikt Ji, Lin Danuser, Gaudenz Schwarz, Ulrich S. Waterman, Clare M. TI Traction stress in focal adhesions correlates biphasically with actin retrograde flow speed SO JOURNAL OF CELL BIOLOGY LA English DT Article ID FLUORESCENT SPECKLE MICROSCOPY; CELL-MIGRATION; DYNAMICS; PROTRUSION; FORCE AB How focal adhesions (FAs) convert retrograde filamentous actin (F-actin) flow into traction stress on the extracellular matrix to drive cell migration is unknown. Using combined traction force and fluorescent speckle microscopy, we observed a robust biphasic relationship between F-actin speed and traction force. F-actin speed is inversely related to traction stress near the cell edge where FAs are formed and F-actin motion is rapid. In contrast, larger FAs where the F-actin speed is low are marked by a direct relationship between F-actin speed and traction stress. We found that the biphasic switch is determined by a threshold F-actin speed of 8-10 nm/s, independent of changes in FA protein density, age, stress magnitude, assembly/disassembly status, or subcellular position induced by pleiotropic perturbations to Rho family guanosine triphosphatase signaling and myosin II activity. Thus, F-actin speed is a fundamental regulator of traction force at FAs during cell migration. C1 [Gardel, Margaret L.] Univ Chicago, Dept Phys, Chicago, IL 60637 USA. [Sabass, Benedikt; Schwarz, Ulrich S.] Univ Heidelberg, BIOQUANT, D-69120 Heidelberg, Germany. [Sabass, Benedikt; Schwarz, Ulrich S.] Univ Karlsruhe, Inst Zool, D-76131 Karlsruhe, Germany. [Sabass, Benedikt; Schwarz, Ulrich S.] Karlsruhe Inst Technol, D-76131 Karlsruhe, Germany. [Ji, Lin; Danuser, Gaudenz] Scripps Res Inst, Dept Cell Biol, La Jolla, CA 92037 USA. [Waterman, Clare M.] NHLBI, NIH, Bethesda, MD 20892 USA. RP Gardel, ML (reprint author), Univ Chicago, Dept Phys, Chicago, IL 60637 USA. EM gardel@uchicago.edu; watermancm@nhlbi.nih.gov RI Gardel, Margaret/D-1703-2012; Schwarz, Ulrich/K-4111-2014; OI Schwarz, Ulrich/0000-0003-1483-640X; Waterman, Clare/0000-0001-6142-6775 FU National Institutes of Health (NIH)/National Heart, Lung, and Blood Institute (C. M. Waterman); Burroughs Wellcome Fund Career Award at the Scientific Interface; Jane Coffin Childs Fellowship; NIH Director's Pioneer Award [DP10D00354]; Center for Modelling and Simulation in the Biosciences at Heidelberg (U. S. Schwarz); [R01 GM71868] FX This work was supported by the intramural research program of the National Institutes of Health (NIH)/National Heart, Lung, and Blood Institute (C. M. Waterman); Burroughs Wellcome Fund Career Award at the Scientific Interface, Jane Coffin Childs Fellowship, and NIH Director's Pioneer Award (DP10D00354) to M. L. Gardel; grant R01 GM71868 to G. Danuser; and the Center for Modelling and Simulation in the Biosciences at Heidelberg (U. S. Schwarz). NR 26 TC 195 Z9 195 U1 0 U2 22 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 15 PY 2008 VL 183 IS 6 BP 999 EP 1005 DI 10.1083/jcb.200810060 PG 7 WC Cell Biology SC Cell Biology GA 384ZQ UT WOS:000261783100007 PM 19075110 ER PT J AU Zhang, NG Kuznetsov, SG Sharan, SK Li, KY Rao, PH Pati, D AF Zhang, Nenggang Kuznetsov, Sergey G. Sharan, Shyam K. Li, Kaiyi Rao, Pulivarthi H. Pati, Debananda TI A handcuff model for the cohesin complex SO JOURNAL OF CELL BIOLOGY LA English DT Article ID SISTER-CHROMATID COHESION; DOUBLE-STRAND BREAKS; SACCHAROMYCES-CEREVISIAE; CHROMOSOME ARMS; SILENT CHROMATIN; SMC COMPLEXES; NIPPED-B; PROTEINS; ANAPHASE; RING AB The cohesin complex is responsible for the accurate separation of sister chromatids into two daughter cells. Several models for the cohesin complex have been proposed, but the one-ring embrace model currently predominates the field. However, the static configuration of the embrace model is not flexible enough for cohesins to perform their functions during DNA replication, transcription, and DNA repair. We used coimmunoprecipitation, a protein fragment complement assay, and a yeast two-hybrid assay to analyze the protein-protein interactions among cohesin subunits. The results show that three of the four human cohesin core subunits (Smc1, Smc3, and Rad21) interact with themselves in an Scc3 (SA1/SA2)-dependent manner. These data support a two-ring handcuff model for the cohesin complex, which is flexible enough to establish and maintain sister chromatid cohesion as well as ensure the fidelity of chromosome segregation in higher eukaryotes. C1 [Zhang, Nenggang; Li, Kaiyi; Rao, Pulivarthi H.; Pati, Debananda] Baylor Coll Med, Texas Childrens Canc Ctr, Dept Pediat Hematol Oncol, Houston, TX 77030 USA. [Kuznetsov, Sergey G.; Sharan, Shyam K.] NCI, Ctr Canc Res, Mouse Canc Genet Program, Frederick, MD 21702 USA. RP Pati, D (reprint author), Baylor Coll Med, Texas Childrens Canc Ctr, Dept Pediat Hematol Oncol, Houston, TX 77030 USA. EM pati@bcm.tmc.edu FU Baylor College of Medicine; National Cancer Institute [1RO1 CA109478] FX This study was supported by Baylor College of Medicine startup funds and a grant from the National Cancer Institute (1RO1 CA109478) awarded to D. Pati. NR 47 TC 72 Z9 75 U1 0 U2 7 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 15 PY 2008 VL 183 IS 6 BP 1019 EP 1031 DI 10.1083/jcb.200801157 PG 13 WC Cell Biology SC Cell Biology GA 384ZQ UT WOS:000261783100009 PM 19075111 ER PT J AU Evdokimov, E Sharma, P Lockett, SJ Lualdi, M Kuehn, MR AF Evdokimov, Evgenij Sharma, Prashant Lockett, Stephen J. Lualdi, Margaret Kuehn, Michael R. TI Loss of SUMO1 in mice affects RanGAP1 localization and formation of PML nuclear bodies, but is not lethal as it can be compensated by SUMO2 or SUMO3 SO JOURNAL OF CELL SCIENCE LA English DT Article DE SUMO; RanGAP1; PML ID UBIQUITIN-LIKE PROTEIN; MODIFIER SUMO-1; TARGET PROTEINS; PORE COMPLEX; CANCER; UBC9; DYNAMICS; DESUMOYLATION; CONJUGATION; PROSTATE AB Conjugation of the small ubiquitin-like modifier (SUMO) to target proteins regulates numerous biological processes and has been implicated in tumorigenesis and metastasis. The three SUMO isoforms in vertebrates, SUMO1 and the highly similar SUMO2 and SUMO3, can be conjugated to unique as well as overlapping subsets of target proteins. Yet, it is still not clear whether roles for each family member are distinct or whether redundancy exists. Here we describe a mutant mouse line that completely lacks SUMO1, but surprisingly is viable and lacks any overt phenotype. Our study points to compensatory utilization of SUMO2 and/or SUMO3 for sumoylation of SUMO1 targets. The ability of SUMO isoforms to substitute for one another has important implications for rational targeting of the SUMO pathway. C1 [Evdokimov, Evgenij; Sharma, Prashant; Kuehn, Michael R.] NCI, Lab Prot Dynam & Signaling, NIH, Frederick, MD 21702 USA. [Lockett, Stephen J.] SAIC Frederick, Adv Technol Program, Opt Microscopy & Anal Lab, Frederick, MD 21702 USA. [Lualdi, Margaret] SAIC Frederick, Lab Anim Sci Program, Frederick, MD 21702 USA. RP Kuehn, MR (reprint author), NCI, Lab Prot Dynam & Signaling, NIH, Frederick, MD 21702 USA. EM mkuehn@mail.nih.gov RI Kuehn, Michael/A-4573-2014 OI Kuehn, Michael/0000-0002-7703-9160 FU Intramural NIH HHS; NCI NIH HHS [N01-CO-12400] NR 46 TC 61 Z9 62 U1 1 U2 4 PU COMPANY OF BIOLOGISTS LTD PI CAMBRIDGE PA BIDDER BUILDING CAMBRIDGE COMMERCIAL PARK COWLEY RD, CAMBRIDGE CB4 4DL, CAMBS, ENGLAND SN 0021-9533 J9 J CELL SCI JI J. Cell Sci. PD DEC 15 PY 2008 VL 121 IS 24 BP 4106 EP 4113 DI 10.1242/jcs.038570 PG 8 WC Cell Biology SC Cell Biology GA 379EE UT WOS:000261378700013 PM 19033381 ER PT J AU Scheidweiler, KB Barnes, AJ Huestis, MA AF Scheidweiler, Karl B. Barnes, Allan J. Huestis, Marilyn A. TI A validated gas chromatographic-electron impact ionization mass spectrometric method for methamphetamine, methylenedioxymethamphetamine (MDMA), and metabolites in mouse plasma and brain SO JOURNAL OF CHROMATOGRAPHY B-ANALYTICAL TECHNOLOGIES IN THE BIOMEDICAL AND LIFE SCIENCES LA English DT Article DE Methylenedioxymethamphetamine; Methamphetamine; Gas chromatography; Mass spectrometry; Tissue; Mouse ID TRANSPORTER KNOCKOUT MICE; NITRIC-OXIDE SYNTHASE; 3,4-METHYLENEDIOXYMETHAMPHETAMINE MDMA; INDUCED NEUROTOXICITY; MAIN METABOLITES; URINARY-EXCRETION; DEFICIENT MICE; DESIGNER DRUGS; NULL MUTATION; AMPHETAMINE AB A method was developed and fully validated for simultaneous quantification of methamphetamine (MAMP), amphetamine, hydroxy-methamphetamine, methylenedioxymethamphetamine (MDMA, ecstasy), methylenedioxyamphetamine, 3-hydroxy-4-methoxy-methamphetamine, and 3-hydroxy-4-methoxy-amphetamine in 100 mu L mouse plasma and 7.5 mg brain. Solid phase extraction and gas chromatography-electron impact ionization mass spectrometry in selected-ion monitoring mode achieved plasma linear ranges of 10-20 to 20,000 ng/mL and 0.1-0.2 to 200 ng/mg in brain. Recoveries were greater than 91%, bias 92.3-110.4%, and imprecision less than 5.3% coefficient of variation. This method was used for measuring MAMP and MDMA and metabolites in plasma and brain during mouse neurotoxicity studies. Published by Elsevier B.V. C1 [Scheidweiler, Karl B.; Barnes, Allan J.; Huestis, Marilyn A.] NIDA, Intramural Res Program, NIH, Biomed Res Ctr, Baltimore, MD 21224 USA. RP Huestis, MA (reprint author), NIDA, Intramural Res Program, NIH, Biomed Res Ctr, 251 Bayview Blvd,Suite 200,Room 05a-721, Baltimore, MD 21224 USA. EM mhuestis@intra.nida.nih.gov FU Intramural Research Program of the National Institute on Drug Abuse; National Institutes of Health FX The authors thank the co-investigators of the MAMP and MDMA neurotoxicity study conducted at the Intramural Research Program, National Institute on Drug Abuse, jean Lud Cadet and Bruce Ladenheim for generously providing mouse plasma and brain specimens for proof of method. This research was supported by the Intramural Research Program of the National Institute on Drug Abuse, National Institutes of Health. NR 51 TC 15 Z9 16 U1 0 U2 1 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 2008 VL 876 IS 2 BP 266 EP 276 DI 10.1016/j.jchromb.2008.11.001 PG 11 WC Biochemical Research Methods; Chemistry, Analytical SC Biochemistry & Molecular Biology; Chemistry GA 386PM UT WOS:000261895100018 PM 19026602 ER PT J AU Huter, EN Stummvoll, GH DiPaolo, RJ Glass, DD Shevach, EM AF Huter, Eva N. Stummvoll, Georg H. DiPaolo, Richard J. Glass, Deborah D. Shevach, Ethan M. TI Cutting Edge: Antigen-Specific TGF beta-Induced Regulatory T Cells Suppress Th17-Mediated Autoimmune Disease SO JOURNAL OF IMMUNOLOGY LA English DT Article ID DENDRITIC CELLS; GASTRITIS; PREVENT; TH17 AB CD4(+) T cells from the TCR transgenic TxA23 mouse recognize a peptide from the H/K-ATPase alpha-chain. When TxA23 CD4(+) thymocytes are differentiated into Th1, Th2, and Th17 lines, all three subpopulations induced autoimmune gastritis (AIG) upon transfer into nu/nu recipients. The induction of AIG by naive T cells or by Th1 or Th2 cell lines could be prevented by the cotransfer of polyclonal Foxp3(+) T regulatory cells (nTreg), whereas Th17-induced AIG was resistant to suppression. We compared the capacity of different types of Treg to suppress Th17-mediated AIG. Cotransfer of either nTreg or polyclonal TGF beta-induced Treg (iTreg) did not prevent AIG, while cotransfier of TGF beta-induced Ag-specific TxA23 iTreg completely prevented the development of disease. Ag-specific iTreg were able to suppress Th17-mediated disease when injected 6 days after the Th17 effectors. The implications of these results for the use of Treg for the cellular biotherapy of autoimmune disease are discussed. The Journal of Immunology, 2008, 181: 8209-8213. C1 [Huter, Eva N.; Glass, Deborah D.; Shevach, Ethan M.] NIAID, Immunol Lab, Cellular Immunol Sect, NIH, Bethesda, MD 20892 USA. [Stummvoll, Georg H.] Med Univ Vienna, Dept Rheumatol, Vienna, Austria. [DiPaolo, Richard J.] St Louis Univ, Sch Med, St Louis, MO 63104 USA. RP Shevach, EM (reprint author), NIAID, Immunol Lab, Cellular Immunol Sect, NIH, Bldg 10,Room 11N315, Bethesda, MD 20892 USA. EM eshevach@niaid.nih.gov FU Intramural NIH HHS [ZIA AI000224-28] NR 13 TC 81 Z9 82 U1 0 U2 3 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 2008 VL 181 IS 12 BP 8209 EP 8213 PG 5 WC Immunology SC Immunology GA 382CQ UT WOS:000261583000007 PM 19050237 ER PT J AU Chen, QY Cannons, JL Paton, JC Akiba, H Schwartzberg, PL Snapper, CM AF Chen, Quanyi Cannons, Jennifer L. Paton, James C. Akiba, Hisaya Schwartzberg, Pamela L. Snapper, Clifford M. TI A Novel ICOS-Independent, but CD28-and SAP-Dependent, Pathway of T Cell-Dependent, Polysaccharide-Specific Humoral Immunity in Response to Intact Streptococcus pneumoniae versus Pneumococcal Conjugate Vaccine SO JOURNAL OF IMMUNOLOGY LA English DT Article ID LINKED LYMPHOPROLIFERATIVE DISEASE; ZONE B-CELLS; IN-VIVO ANTIPOLYSACCHARIDE; IG ISOTYPE RESPONSES; MARGINAL-ZONE; LYMPH-NODE; ANTIPROTEIN RESPONSES; MECHANISM DISTINCT; ANTIBODY-RESPONSES; GERMINAL-CENTERS AB Polysaccharide (PS)- and protein-specific murine IgG responses to intact Streptococcus pneumoniae (Pn) are both dependent on CD4(+) T cell help, B7-dependent costimulation, and CD40/CD40 ligand interactions. However, the primary PS-specific, relative to protein-specific, IgG response terminates more rapidly, requires a shorter period of T cell help and B7-dependent costimulation, and fails to generate memory. In light of the critical role for ICOS/ICOS ligand interactions in sustaining T cell-dependent Ig responses and promoting germinal center reactions, we hypothesized that this interaction was nonessential for PS-specific IgG responses to Pn. We now demonstrate that ICOS(-/-), relative to wild-type, mice elicit a normal PS-specific IgG isotype response to Pn, despite marked inhibition of both the primary and secondary IgG anti-protein (i.e., PspA, PspC, and PsaA) response. A blocking anti-ICOS ligand mAb injected during primary Pn immunization inhibits both the primary anti-protein response and the generation of protein-specific memory, but has no effect when injected during secondary immunization. In contrast to Pn, both PS-and protein-specific IgG responses to a pneumococcal conjugate vaccine are inhibited in ICOS(-/-) mice. ICOS(-/-) mice immunized with intact Pn or conjugate exhibit nearly complete abrogation in germinal center formation. Finally, although mice that lack the adaptor molecule SAP (SLAM-associated protein) resemble ICOS-/- mice (and can exhibit decreased ICOS expression), we observe that the PS-specific, as well as protein-specific, IgG responses to both Pn and conjugate are markedly defective in SAP(-/-) mice. These data define a novel T cell-, SAP-, and B7-dependent, but ICOS-independent, extrafollicular pathway of Ig induction. The Journal of Immunology, 2008, 181: 8258-8266. C1 [Chen, Quanyi; Snapper, Clifford M.] Uniformed Serv Univ Hlth Sci, Dept Pathol, Bethesda, MD 20814 USA. [Cannons, Jennifer L.; Schwartzberg, Pamela L.] Natl Human Genome Res Inst, NIH, Bethesda, MD 20814 USA. [Paton, James C.] Univ Adelaide, Sch Mol & Biomed Sci, Adelaide, SA, Australia. [Akiba, Hisaya] Juntendo Univ, Sch Med, Dept Immunol, Tokyo 113, Japan. RP Snapper, CM (reprint author), Uniformed Serv Univ Hlth Sci, Dept Pathol, 4301 Jones Bridge Rd, Bethesda, MD 20814 USA. EM csnapper@usuhs.mil RI Paton, James/A-9920-2008 FU National Institutes of Health [1R01 AI49192]; Uniformed Services University of the Health Sciences Dean's Research; Education Endowment Fund; National Human Genome Research Institute FX This study wits supported by National Institutes of Health Grants 1R01 AI49192 (to C.M.S.) and the Uniformed Services University of the Health Sciences Dean's Research and Education Endowment Fund (to C.M.S.) and by funding from the intramural program of the National Human Genome Research Institute (to P.L.S.). NR 65 TC 23 Z9 24 U1 0 U2 0 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 2008 VL 181 IS 12 BP 8258 EP 8266 PG 9 WC Immunology SC Immunology GA 382CQ UT WOS:000261583000012 PM 19050242 ER PT J AU Yamazaki, T Yang, XO Chung, Y Fukunaga, A Nurieva, R Pappu, B Martin-Orozco, N Kang, HS Ma, L Panopoulos, AD Craig, S Watowich, SS Jetten, AM Tian, Q Dong, C AF Yamazaki, Tomohide Yang, Xuexian O. Chung, Yeonseok Fukunaga, Atsushi Nurieva, Roza Pappu, Bhanu Martin-Orozco, Natalia Kang, Hong Soon Ma, Li Panopoulos, Athanasia D. Craig, Suzanne Watowich, Stephanie S. Jetten, Anton M. Tian, Qiang Dong, Chen TI CCR6 Regulates the Migration of Inflammatory and Regulatory T Cells SO JOURNAL OF IMMUNOLOGY LA English DT Article ID GROWTH-FACTOR-BETA; AUTOIMMUNE INFLAMMATION; IL-17-PRODUCING CELLS; IMMUNE-RESPONSES; HELPER-CELLS; ROR-GAMMA; LINEAGE; DIFFERENTIATION; RECEPTOR; CYTOKINE AB Th17 and regulatory T (Treg) cells play opposite roles in autoimmune diseases. However, the mechanisms underlying their proper migration to inflammatory tissues are unclear. In this study, we report that these two T cell subsets both express CCR6. CCR6 expression in Th17 cells is regulated by TGF-beta and requires two nuclear receptors, ROR alpha and ROR gamma. Th17 cells also express the CCR6 ligand CCL20, which is induced synergistically by TGF-beta and IL-6, which requires STAT3, ROR gamma and IL-21. Th17 cells, by producing CCL20, promote migration of Th17 and Treg cells in vitro in a CCR6-dependent manner. Lack of CCR6 in Th17 cells reduces the severity of experimental autoimmune encephalomyelitis and Th17 and Treg recruitment into inflammatory tissues. Similarly, CCR6 on Treg cells is also important for their recruitment into inflammatory tissues. Our data indicate an important role of CCR6 in Treg and Th17 cell migration. The Journal of Immunology, 2008, 181: 8391-8401. C1 [Yamazaki, Tomohide; Yang, Xuexian O.; Chung, Yeonseok; Fukunaga, Atsushi; Nurieva, Roza; Pappu, Bhanu; Martin-Orozco, Natalia; Panopoulos, Athanasia D.; Watowich, Stephanie S.; Dong, Chen] Univ Texas Houston, MD Anderson Canc Ctr, Dept Immunol, Houston, TX 77030 USA. [Kang, Hong Soon; Jetten, Anton M.] Natl Inst Environm Sci, Cell Biol Sect, Lab Resp Biol, NIH, Res Triangle Pk, NC 27709 USA. [Ma, Li; Tian, Qiang] Inst Syst Biol, Seattle, WA 98103 USA. RP Dong, C (reprint author), Univ Texas MD Anderson Canc Ctr, Dept Immunol, Houston, TX 77030 USA. EM cdong@mdanderson.org RI dong, chen /B-3181-2009; Martin Orozco, Natalia/E-4794-2010; OI dong, chen /0000-0002-0084-9130; Jetten, Anton/0000-0003-0954-4445; Chung, Yeonseok/0000-0001-5780-4841; Watowich, Stephanie/0000-0003-1969-659X FU National Institutes of Health; National Institute on Environmental Health Sciences; Leukemia and Lymphoma Society; Anderson Cancer Center; Gillson Longenbaugh Foundation; Odyssey Program; Kimberly-Clark Foundation Award for Scientific Achievement at MD Anderson Cancer Center FX This work was supported by research grants from the National Institutes of Health (to C.D.), an Intramural Research Program of the National Institute on Environmental Health Sciences, National Institutes of Health (to A.M.J.), the Leukemia and Lymphoma Society (to C.D.) and M.D. Anderson Cancer Center (to C.D. and S.S.W.), and the Gillson Longenbaugh Foundation (to S.S.W.). T.Y. received a fellowship from the Odyssey Program and The Kimberly-Clark Foundation Award for Scientific Achievement at MD Anderson Cancer Center. R.N. is a recipient of a Scientist Development Grant from the American Heart Association. C.D. is a Trust Fellow of the MD Anderson Cancer Center, a Cancer Research Institute Investigator, a Leukemia and Lymphoma Society Scholar, and an American Lung Association Career Investigator. NR 45 TC 203 Z9 212 U1 1 U2 7 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 2008 VL 181 IS 12 BP 8391 EP 8401 PG 11 WC Immunology SC Immunology GA 382CQ UT WOS:000261583000026 PM 19050256 ER PT J AU Yarovinsky, F Hieny, S Sher, A AF Yarovinsky, Felix Hieny, Sara Sher, Alan TI Recognition of Toxoplasma gondii by TLR11 Prevents Parasite-Induced Immunopathology SO JOURNAL OF IMMUNOLOGY LA English DT Article ID TOLL-LIKE RECEPTORS; NATURAL-KILLER-CELLS; IFN-GAMMA; ACUTE-PANCREATITIS; DENDRITIC CELLS; IMMUNE-SYSTEM; RESISTANCE; INFECTION; PATHOGENS; IL-12 AB TLRs are thought to play a critical role in self/non-self discrimination by sensing microbial infections and initiating both innate and adaptive immunity. In this study, we demonstrate that in the absence of TLR11, a major TLR involved in recognition of Toxoplasma gondii, infection with this protozoan parasite induces an abnormal immunopathological response consisting of pancreatic tissue destruction, fat necrosis, and systemic elevations in inflammatory reactants. We further show that this immunopathology is the result of non-TLR dependent activation of IFN-gamma secretion by NK cells in response to the infection. These findings reveal that in addition to triggering host resistance to infection, TLR recognition can be critical for the prevention of pathogen-induced immune destruction of self tissue. The Journal of Immunology, 2008,181: 8478-8484. C1 [Yarovinsky, Felix] Univ Texas SW Med Ctr Dallas, Dept Immunol, Dallas, TX 75390 USA. [Yarovinsky, Felix; Hieny, Sara; Sher, Alan] NIAID, Parasit Dis Lab, NIH, Bethesda, MD 20892 USA. RP Yarovinsky, F (reprint author), Univ Texas SW Med Ctr Dallas, Dept Immunol, 5323 Harry Hines Blvd, Dallas, TX 75390 USA. EM Felix.Yarovinsky@UTSouthwestern.edu FU National Institute of Allergy and Infectious Diseases intramural program; University of Texas Southwestern Medical Center Endowed Scholars Program FX This project was supported (in part) by the National Institute of Allergy and Infectious Diseases intramural program and by the University of Texas Southwestern Medical Center Endowed Scholars Program. NR 28 TC 18 Z9 24 U1 0 U2 3 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 2008 VL 181 IS 12 BP 8478 EP 8484 PG 7 WC Immunology SC Immunology GA 382CQ UT WOS:000261583000035 PM 19050265 ER PT J AU Furuichi, K Gao, JL Horuk, R Wada, T Kaneko, S Murphy, PM AF Furuichi, Kengo Gao, Ji-Liang Horuk, Richard Wada, Takashi Kaneko, Shuichi Murphy, Philip M. TI Chemokine Receptor CCR1 Regulates Inflammatory Cell Infiltration after Renal Ischemia-Reperfusion Injury SO JOURNAL OF IMMUNOLOGY LA English DT Article ID MICE; NEUTROPHIL; FIBROSIS; FAILURE; KIDNEY; MACROPHAGES; DEFICIENCY; MIGRATION; SURVIVAL; DISEASE AB Neutrophils and macrophages rapidly infiltrate the kidney after renal ischemia-reperfusion injury, however specific molecular recruitment mechanisms have not been fully delineated for these cell types. Here we provide genetic and pharmacologic evidence supporting a positive role for the chemokine receptor CCR1 in macrophage and neutrophil infiltration in a 7 day mouse model of renal ischemia-reperfusion injury. By day 7, injured kidneys from mice lacking CCR1 contained 35% fewer neutrophils and 45% fewer macrophages than injured kidneys from wild-type control mice. Pretreatment of wild-type mice with the specific CCR1 antagonist BX471 also suppressed neutrophil and macrophage infiltration in the model. Injured kidneys from mice lacking CCR1 also had reduced content of the CCR1 ligands CCL3 (MIP-1 alpha) and CCL5 (RANTES) compared with injured kidneys from wild-type controls, suggesting a leukocyte source for these inflammatory chemokines and existence of a CCR1-dependent positive feedback loop for leukocyte infiltration in the model. Local leukocyte proliferation and apoptosis were detected after injury, but were not dependent on CCR1. Also, the extent of necrotic and fibrotic damage and decline in renal function in injured kidneys was similar in wild-type and CCR1-deficient mice. Thus, CCR1 appears to regulate trafficking of macrophages and neutrophils to kidney in a mouse model of renal ischemia-reperfusion injury, however this activity does not appear to affect tissue injury. The Journal of Immunology, 2008, 181: 8670-8676. C1 [Furuichi, Kengo; Gao, Ji-Liang; Murphy, Philip M.] NIAID, Lab Mol Immunol, NIH, Bethesda, MD 20892 USA. [Furuichi, Kengo; Wada, Takashi; Kaneko, Shuichi] Kanazawa Univ, Lab Med Dis Control & Homeostasis, Div Blood Purificat, Kanazawa, Ishikawa, Japan. [Horuk, Richard] Dept Immunol, Richmond, CA 94806 USA. RP Murphy, PM (reprint author), NIAID, Lab Mol Immunol, NIH, Bldg 10,Room 11N113, Bethesda, MD 20892 USA. EM pmm@nih.gov FU National Institute of Allergy and Infectious Diseases, National Institutes of Health FX This research was supported by the Intramural Research Program of the National Institute of Allergy and Infectious Diseases, National Institutes of Health. NR 37 TC 47 Z9 51 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 2008 VL 181 IS 12 BP 8670 EP 8676 PG 7 WC Immunology SC Immunology GA 382CQ UT WOS:000261583000057 PM 19050287 ER PT J AU Starosta, V Pazdrak, K Boldogh, I Svider, T Kurosky, A AF Starosta, Vitaliy Pazdrak, Konrad Boldogh, Istvan Svider, Tetyana Kurosky, Alexander TI Lipoxin A(4) Counterregulates GM-CSF Signaling in Eosinophilic Granulocytes SO JOURNAL OF IMMUNOLOGY LA English DT Article ID COLONY-STIMULATING FACTOR; ASPIRIN-TRIGGERED LIPOXIN; NF-KAPPA-B; TYROSINE PHOSPHORYLATION; GEL-ELECTROPHORESIS; HUMAN NEUTROPHILS; CELL LINE; ACTIVATION; INFLAMMATION; SPECTRIN AB Eosinophils are granulated leukocytes that are involved in many inflammation-associated pathologies including airway inflammation in asthma. Resolution of eosinophilic inflammation and return to homeostasis is in part due to endogenous chemical mediators, for example, lipoxins, resolvins, and protectins. Lipoxins are endogenous eicosanoids that demonstrate antiinflammatory activity and are synthesized locally at sites of inflammation. In view of the importance of lipoxins (LXs) in resolving inflammation, we investigated the molecular basis of LXA(4) action on eosinophilic granulocytes stimulated with GM-CSF employing the eosinophilic leukemia cell line EoL-1 as well as peripheral blood eosinophils. We report herein that LXA(4) (1-100 nM) decreased protein tyrosine phosphorylation in EoL-1 cells stimulated with GM-CSF. Additionally, the expression of a number of GM-CSF-induced cytokines was inhibited by LXA(4) in a dose-dependent manner. Furthermore, using a proteomics approach involving mass spectrometry and immunoblot analysis we identified 11 proteins that were tyrosine phosphorylated after GM-CSF stimulation and whose phosphorylation was significantly inhibited by LXA(4) pretreatment. Included among these 11 proteins were alpha-fodrin (non-erythroid spectrin) and actin. Microscopic imaging showed that treatment of EoL-1 cells or blood eosinophils with GM-CSF resulted in the reorganization of actin and the translocation of alpha-fodrin from the cytoplasm to the plasma membrane. Importantly, alpha-fodrin translocation was prevented by LXA(4) but actin reorganization was not. Thus, the mechanism of LXA(4) action likely involves prevention of activation of eosinophilic granulocytes by GM-CSF through inhibition of protein tyrosine phosphorylation and modification of some cytoskeletal components. The Journal of Immunology, 2008, 181: 8688-8699. C1 [Starosta, Vitaliy; Pazdrak, Konrad; Kurosky, Alexander] Univ Texas Galveston, Med Branch, Dept Biochem & Mol Biol, Galveston, TX 77555 USA. [Boldogh, Istvan] Univ Texas Galveston, Med Branch, Dept Microbiol & Immunol, Galveston, TX 77555 USA. [Svider, Tetyana; Kurosky, Alexander] Univ Texas Galveston, Med Branch, NHLBI, Prote Ctr, Galveston, TX 77555 USA. RP Kurosky, A (reprint author), Univ Texas Galveston, Med Branch, Dept Biochem & Mol Biol, 301 Univ Blvd, Galveston, TX 77555 USA. EM akurosky@utmb.edu FU National Institutes of Health National Heart, Lung, and Blood Institute's Proteomics Initiative [N01-HV-28184]; National Institute for Environmental Health Sciences Center [P30-ES006676]; National Institute of Allergy and Infectious Diseases [P01 AI062885] FX This study was supported by the National Institutes of Health National Heart, Lung, and Blood Institute's Proteomics Initiative N01-HV-28184 (to A.K.), National Institute for Environmental Health Sciences Center Grant P30-ES006676 (to J. Halpert), National Institute of Allergy and Infectious Diseases Grant P01 AI062885 (to A. Brasier) and a James W. McLaughlin postdoctoral fellowship grant to V. Starosta. NR 50 TC 23 Z9 23 U1 0 U2 0 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 2008 VL 181 IS 12 BP 8688 EP 8699 PG 12 WC Immunology SC Immunology GA 382CQ UT WOS:000261583000059 PM 19050289 ER PT J AU Miura, K Zhou, H Moretz, SE Diouf, A Thera, MA Dolo, A Doumbo, O Malkin, E Diemert, D Miller, LH Mullen, GED Longli, CA AF Miura, Kazutoyo Zhou, Hong Moretz, Samuel E. Diouf, Ababacar Thera, Mahamadou A. Dolo, Amagana Doumbo, Ogobara Malkin, Elissa Diemert, David Miller, Louis H. Mullen, Gregory E. D. Longli, Carole A. TI Comparison of Biological Activity of Human Anti-Apical Membrane Antigen-1 Antibodies Induced by Natural Infection and Vaccination SO JOURNAL OF IMMUNOLOGY LA English DT Article ID PLASMODIUM-FALCIPARUM MALARIA; BLOOD-STAGE MALARIA; MEROZOITE SURFACE PROTEIN-1; DOMAIN-III; RECOMBINANT; CANDIDATE; SPECIFICITY; PROTECTION; RESPONSES; MONKEYS AB Vaccines represent a significant potential means of decreasing global morbidity and mortality due to malaria. Clinical trials in the United States with Plasmodium falciparum Apical Membrane Antigen 1 (AMA1) showed that the vaccine induced biologically active Abs judged by an in vitro parasite growth inhibition assay (GIA). However, the same vaccine in Malian adults did not increase biological activity, although it elevated ELISA titers. Because GIA has been used to evaluate the biological activity of Abs induced by blood stage malarial vaccine candidates, we explored this discrepancy in this study. We affinity purified AMA1-specific Abs from both U.S. vaccinees and nonvaccinated individuals living in a malaria-endemic area of Mali and performed ELISA and GIA. Both AMA1-specifc Abs induced by vaccination (U.S.) and by natural infection (Mali) have comparable biological activity in GIA when the ELISA titer is normalized. However, a fraction of Malians' IgG that did not bind to AMA1 protein (Mali-non-AMA1 IgG) reduced the biological activity of the AMA1 Abs from U.S. vaccinees; in contrast, U.S.-non-AMA1 IgGs did not show a reduction of the biological activity. Further investigation revealed that the reduction was due to malaria-specitic IgGs in the Mali-non-AMA1 IgGs. The fact that both U.S.- and Mali-AMA1-specific Abs showed comparable biological activity supports further development of AMA1-based vaccines. However, the reduction of biological activity of AMA1-specific Ab by other malaria-specific IgGs likely explains the limited effect on growth-inhibitory activity of Abs induced by AMA1 vaccination in Malian adults and may complicate efforts to develop a blood stage malaria vaccine. The Journal of Immunology, 2008, 181: 8776-8783. C1 [Miura, Kazutoyo; Malkin, Elissa; Diemert, David; Miller, Louis H.; Mullen, Gregory E. D.] NIAID, Malaria Vaccine Dev Branch, NIH, Bethesda, MD 20892 USA. [Zhou, Hong; Moretz, Samuel E.; Diouf, Ababacar; Longli, Carole A.] NIAID, Lab Malaria & Vector Res, NIH, Bethesda, MD 20892 USA. [Thera, Mahamadou A.; Dolo, Amagana; Doumbo, Ogobara] Univ Bamako, Dept Hematol & Parasitol, Malaria Res & Training Ctr, Bamako, Mali. RP Miura, K (reprint author), 12441 Parklawn Dr,Twinbrook 2,Room 107, Rockville, MD 20852 USA. EM kmiura@niaid.nih.gov FU PATH/Malaria Vaccine Initiative; National Institute of Allergy and Infectious Diseases, National Institutes of Health FX This study was funded in part by the PATH/Malaria Vaccine Initiative and the Intramural program of the National Institute of Allergy and Infectious Diseases, National Institutes of Health. NR 31 TC 39 Z9 39 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 2008 VL 181 IS 12 BP 8776 EP 8783 PG 8 WC Immunology SC Immunology GA 382CQ UT WOS:000261583000069 PM 19050299 ER PT J AU Hadigan, C AF Hadigan, Colleen TI Peroxisome Proliferator-Activated Receptor gamma Agonists and the Treatment of HIV-Associated Lipoatrophy: Unraveling the Molecular Mechanism of Their Shortcomings SO JOURNAL OF INFECTIOUS DISEASES LA English DT Editorial Material ID REVERSE-TRANSCRIPTASE INHIBITORS; PLACEBO-CONTROLLED TRIAL; INFECTED PATIENTS; DOUBLE-BLIND; MITOCHONDRIAL TOXICITY; ANTIRETROVIRAL-THERAPY; ADIPOSE-TISSUE; LIPODYSTROPHY; ROSIGLITAZONE; ANALOG C1 NIAID, NIH, Immunoregulat Lab, Bethesda, MD 20892 USA. RP Hadigan, C (reprint author), NIAID, NIH, Immunoregulat Lab, 10 Ctr Dr,Bldg 10 Rm 11C 103, Bethesda, MD 20892 USA. EM hadiganc@niaid.nih.gov NR 17 TC 4 Z9 4 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 1427 E 60TH ST, CHICAGO, IL 60637-2954 USA SN 0022-1899 J9 J INFECT DIS JI J. Infect. Dis. PD DEC 15 PY 2008 VL 198 IS 12 BP 1729 EP 1731 DI 10.1086/593180 PG 3 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 376QB UT WOS:000261197000001 PM 18954262 ER PT J AU Jensen, TB Gottwein, JM Scheel, TKH Hoegh, AM Eugen-Olsen, J Bukh, J AF Jensen, Tanja B. Gottwein, Judith M. Scheel, Troels K. H. Hoegh, Anne M. Eugen-Olsen, Jesper Bukh, Jens TI Highly Efficient JFH1-Based Cell-Culture System for Hepatitis C Virus Genotype 5a: Failure of Homologous Neutralizing-Antibody Treatment to Control Infection SO JOURNAL OF INFECTIOUS DISEASES LA English DT Article; Proceedings Paper CT 58th Annual Meeting of the American-Association-for-the-Study-of-Liver-Diseases CY NOV 02-06, 2007 CL Boston, MA SP Amer Assoc Study Liver Dis ID SCAVENGER RECEPTOR-BI; SEQUENCE-ANALYSIS; IN-VITRO; DETERMINANTS; ENHANCEMENT; RECOMBINANT; PERSISTENCE; INTERFERON; CHALLENGE; CLEARANCE AB Background. Recently, a hepatitis C virus (HCV) cell-culture system was developed that employed strain JFH1 ( genotype 2a), and JFH1-based intra-and intergenotypic recombinants now permit functional studies of the structural genes ( Core, E1, and E2), p7, and NS2 of genotypes 1-4. The goal was to adapt the system to employ genotype 5. Methods. Huh7.5 cells infected with SA13/JFH1, containing Core-NS2 of strain SA13 ( genotype 5a), were monitored for Core expression and for supernatant infectivity and HCV-RNA titers. Adaptive mutations of SA13/JFH1 were identified by sequence analysis of recovered genomes and reverse-genetic studies. Receptor blockage was performed with anti-CD81 and anti-SR-BI. For neutralization experiments, SA13/JFH1 or JFH1-based viruses of other genotypes were incubated with patient sera. Results. SA13/JFH1 with NS2 and NS3 mutations yielded infectivity titers > 10(5) TCID(50)/mL. Infection with SA13/JFH1 was inhibited by CD81 blocking and SR-BI blocking, respectively, and by preincubation with genotype 5a chronic-phase patient sera. Such sera had varying cross-genotype neutralization potential. However, preincubation and treatment with homologous neutralizing antibodies could not control SA13/JFH1 infection in culture. Conclusion. The SA13/JFH1 culture permits genotype 5a-specific studies of Core-NS2 function and interfering agents. The ability of HCV to spread in vivo during treatment with neutralizing antibodies was confirmed in vitro. C1 [Jensen, Tanja B.; Gottwein, Judith M.; Scheel, Troels K. H.; Eugen-Olsen, Jesper; Bukh, Jens] Copenhagen Univ Hosp, Dept Infect Dis, Copenhagen Hepatitis C Program CO HEP, DK-2650 Hvidovre, Denmark. [Jensen, Tanja B.; Gottwein, Judith M.; Scheel, Troels K. H.; Eugen-Olsen, Jesper; Bukh, Jens] Copenhagen Univ Hosp, Clin Res Ctr, DK-2650 Hvidovre, Denmark. [Hoegh, Anne M.] Copenhagen Univ Hosp, Dept Clin Microbiol, DK-2650 Hvidovre, Denmark. [Scheel, Troels K. H.; Bukh, Jens] Univ Copenhagen, Dept Int Hlth Immunol & Microbiol, Fac Hlth Sci, Copenhagen, Denmark. [Bukh, Jens] NIAID, Hepatitis Viruses Sect, Infect Dis Lab, NIH, Bethesda, MD 20892 USA. RP Bukh, J (reprint author), Copenhagen Univ Hosp, Dept Infect Dis, Copenhagen Hepatitis C Program CO HEP, Kettegaard Alle 30, DK-2650 Hvidovre, Denmark. EM jbukh@niaid.nih.gov OI Eugen-Olsen, jesper/0000-0002-4630-4275; Scheel, Troels/0000-0003-1545-4067 NR 35 TC 63 Z9 64 U1 0 U2 6 PU UNIV CHICAGO PRESS PI CHICAGO PA 1427 E 60TH ST, CHICAGO, IL 60637-2954 USA SN 0022-1899 J9 J INFECT DIS JI J. Infect. Dis. PD DEC 15 PY 2008 VL 198 IS 12 BP 1756 EP 1765 DI 10.1086/593021 PG 10 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 376QB UT WOS:000261197000003 PM 19032070 ER PT J AU Horkay, F Basser, PJ AF Horkay, Ferenc Basser, Peter J. TI Ionic and pH Effects on the Osmotic Properties and Structure of Polyelectrolyte Gels SO JOURNAL OF POLYMER SCIENCE PART B-POLYMER PHYSICS LA English DT Article DE neutron scattering; osmotic pressure; phase behavior; phase transition; polyelectrolyte gel; polyelectrolytes; small-angle neutron scattering ID PHYSIOLOGICAL SALT-SOLUTIONS; ANGLE NEUTRON-SCATTERING; POLYMER-CHAIN; POLYACRYLATE HYDROGELS; PHASE-TRANSITION; THERMODYNAMIC OBSERVATIONS; COLLAPSE; SWOLLEN; NETWORKS; BEHAVIORS AB We investigate the effects of salt concentration and pH on neutralized poly(acrylic acid) (PAA) gels in near physiological salt solutions. Either adding calcium ions or decreasing the pH is found to induce reversible volume transitions but the nature of these transitions seems to be different. For example, the osmotic pressure exhibits a simple power law dependence on the concentration as the transition is approached in both systems, but the power law exponent it is substantially different in the two cases. On decreasing the pH the value of n gradually increases from 2.1 (at pH = 7) to 3.2 (at pH = 1). By contrast, n decreases with increasing calcium ion concentration from 2.1 (in 100 mM NaCl solution) to 1.6 (0.8 mM CaCl(2) ill 100 mM NaCl solution). In both systems, a strong increase of the small-angle neutron scattering intensity (SANS) is observed near the volume transition. The SANS results reveal that calcium ions favor the formation of linearly aligned regions in PAA gels. (C) 2008 Wiley Periodicals, Inc. J Polym Sci Part B: Polym Phys 46: 2803-2810, 2008 C1 [Horkay, Ferenc; Basser, Peter J.] NICHD, Sect Tissue Biophys & Biomimet, Lab Integrat & Med Biophys, NIH, Bethesda, MD 20892 USA. RP Horkay, F (reprint author), NICHD, Sect Tissue Biophys & Biomimet, Lab Integrat & Med Biophys, NIH, 13 S Dr, Bethesda, MD 20892 USA. EM horkay@helix.nih.gov RI Basser, Peter/H-5477-2011 FU Intramural Research Program of the NICHD, NIH; National Institute of Standards and Technology; U.S. Department of Commerce; National Science Foundation [DMR-0454672] FX This research was supported by the Intramural Research Program of the NICHD, NIH. The authors acknowledge the support of the National Institute of Standards and Technology, U.S. Department of Commerce, in providing the neutron research facilities used in this work. This work utilized facilities supported in part by the National Science Foundation under Agreement No. DMR-0454672. The authors are grateful to Dr. Jack F. Douglas (NIST) for helpful comments. NR 35 TC 3 Z9 3 U1 4 U2 24 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0887-6266 J9 J POLYM SCI POL PHYS JI J. Polym. Sci. Pt. B-Polym. Phys. PD DEC 15 PY 2008 VL 46 IS 24 BP 2803 EP 2810 DI 10.1002/polb.21590 PG 8 WC Polymer Science SC Polymer Science GA 383WQ UT WOS:000261705400016 PM 20016687 ER PT J AU Regenold, WT Phatak, P Makley, MJ Stone, RD Kling, MA AF Regenold, William T. Phatak, Pornima Makley, Michael J. Stone, Roger D. Kling, Mitchel A. TI Cerebrospinal fluid evidence of increased extra-mitochondrial glucose metabolism implicates mitochondrial dysfunction in multiple sclerosis disease progression SO JOURNAL OF THE NEUROLOGICAL SCIENCES LA English DT Article DE Multiple sclerosis; Metabolism; Mitochondrial; Polyol; Lactate; Glucose; Energy; Progression; Degeneration ID MAGNETIC-RESONANCE SPECTROSCOPY; CENTRAL-NERVOUS-SYSTEM; STROKE-LIKE EPISODES; LACTIC-ACIDOSIS; AXONAL DEGENERATION; POLYOLS; DNA; LACTATE; PLASMA; ENCEPHALOMYOPATHY AB In contrast to relapse, the mechanisms of multiple sclerosis (MS) disease progression are less understood and appear not to be exclusively inflammatory in nature. In this pilot study we investigated the relationship between disturbed CNS energy metabolism and MS disease progression. We tested the hypothesis that cerebrospinal fluid (CSF) concentrations of sorbitol, fructose, and lactate, all metabolites of extramitochondrial glucose metabolism, would be elevated in secondary progressive (SP) MS patients and would be associated with worsening neurologic disability. We measured metabolite concentrations by gas chromatographic/mass spectrometric and enzymatic methods in archived CSF samples from 85 MS patients [31 relapsing-remitting (RR) and 54 SP patients] and 18 healthy controls. We found that concentrations of all three metabolites, but not concentrations of glucose or myoinositol, were significantly increased in CSF from SP and, to a lesser degree, RR patients, compared to controls. Furthermore, CSF concentrations of sorbitol and fructose (polyol pathway metabolites), but not lactate (anaerobic glycolysis metabolite), correlated positively and significantly with Expanded Disability Status Scale (EDSS) score, an index of neurologic disability in MS patients. We conclude that extra-mitochondrial glucose metabolism is increased in MS patients and is associated with disease progression evidenced by increasing EDSS score. As extra-mitochondrial glucose metabolism increases with impaired mitochondrial metabolism of glucose, these findings implicate mitochondrial dysfunction in the pathogenesis of MS disease progression. CSF metabolic profiling may be useful in clarifying the role of mitochondrial pathology in progression and in targeting and monitoring therapies for disease progression that aim to preserve or boost mitochondrial glucose metabolism. (C) 2008 Elsevier B.V. All rights reserved. C1 [Regenold, William T.; Phatak, Pornima] Univ Maryland, Sch Med, Dept Psychiat, Div Geriatr Psychiat, Baltimore, MD 21201 USA. [Regenold, William T.; Phatak, Pornima] Baltimore Vet Affairs Med Ctr, Res Serv, Baltimore, MD 21201 USA. [Makley, Michael J.] Univ Maryland, Sch Med, Dept Neurol, Comprehens Multiple Sclerosis Ctr Baltimore, Baltimore, MD 21201 USA. [Stone, Roger D.] Natl Inst Neurol Disorders & Stroke, Neuroimmunol Branch, Bethesda, MD USA. [Kling, Mitchel A.] Wyeth Pharmaceut, Div Clin Translat Med, Madison, NJ USA. [Kling, Mitchel A.] NIMH, Clin Neuroendocrinol Branch, Bethesda, MD 20892 USA. RP Regenold, WT (reprint author), Univ Maryland, Sch Med, Dept Psychiat, Div Geriatr Psychiat, Baltimore, MD 21201 USA. EM wregenol@psych.umaryland.edu RI Kling, Mitchel/F-4152-2010 OI Kling, Mitchel/0000-0002-2232-1409 FU National Multiple Sclerosis Society [PP0932]; Intramural Research Program of the NIH; NINDS FX The authors thank the individuals who generously donated their CSF; Lisa McFarland, M.S. for GC-MS technical assistance; Andrew P. Goldberg, M.D. and the Baltimore VAMC GRECC for extended loan of the GC-MS system; Roland Martin, M.D. and Laura Tranquill, M.S. of the NINDS Neuroimmunology Branch, for assistance in providing CSF samples for a preliminary Study; W.W. Tourtelotte, M.D., Ph.D. and staff at the Human Brain and Spinal Fluid Resource Center for assistance with samples and clinical information; and the National Multiple Sclerosis Society for funding this study with a Pilot Research Project Award (PP0932) to W.T.R. This research was also supported in part by the Intramural Research Program of the NIH, NINDS. NR 46 TC 29 Z9 29 U1 0 U2 4 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 2008 VL 275 IS 1-2 BP 106 EP 112 DI 10.1016/j.jns.2008.07.032 PG 7 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 384MO UT WOS:000261749100019 PM 18783801 ER PT J AU Darugar, Q Kim, H Gorelick, RJ Landes, C AF Darugar, Qusai Kim, Hannah Gorelick, Robert J. Landes, Christy TI Human T-Cell Lymphotropic Virus Type 1 Nucleocapsid Protein-Induced Structural Changes in Transactivation Response DNA Hairpin Measured by Single-Molecule Fluorescence Resonance Energy Transfer SO JOURNAL OF VIROLOGY LA English DT Article ID NUCLEIC-ACID-CHAPERONE; HIV-1 REVERSE TRANSCRIPTION; ZINC-FINGER STRUCTURES; PLUS-STRAND TRANSFER; COMPLEMENTARY SEQUENCE; SECONDARY STRUCTURE; BINDING-PROPERTIES; RNA; LEUKEMIA; MECHANISM AB Time-resolved single-molecule fluorescence spectroscopy was used to study the human T-cell lymphotropic virus type 1 (HTLV-1) nucleocapsid protein (NC) chaperone activity compared to that of the human immunodeficiency virus type 1 (HIV-1) NC protein. HTLV-1 NC contains two zinc fingers, each having a CCHC binding motif similar to HIV-1 NC. HIV-1 NC is required for recognition and packaging of the viral RNA and is also a nucleic acid chaperone protein that facilitates nucleic acid restructuring during reverse transcription. Because of similarities in structures between the two retroviruses, we have used single-molecule fluorescence energy transfer to investigate the chaperoning activity of the HTLV-1 NC protein. The results indicate that the HTLV-1 NC protein induces structural changes by opening the transactivation response (TAR) DNA hairpin to an even greater extent than HIV-1 NC. However, unlike HIV-1 NC, HTLV-1 NC does not chaperone the strand-transfer reaction involving TAR DNA. These results suggest that, despite its effective destabilization capability, HTLV-1 NC is not as effective at overall chaperone function as is its HIV-1 counterpart. C1 [Darugar, Qusai; Kim, Hannah; Landes, Christy] Univ Houston, Dept Chem, Houston, TX 77204 USA. [Gorelick, Robert J.] NCI Frederick, SAIC Frederick Inc, AIDS & Canc Virus Program, Frederick, MD 21702 USA. RP Landes, C (reprint author), Univ Houston, Dept Chem, 136 Fleming, Houston, TX 77204 USA. EM cflandes@uh.edu RI Landes, Christy/I-5501-2014 FU National Cancer Institute; National Institutes of Health [N01-CO-12400] FX We thank the University of Houston and the Texas Center for Superconductivity for new faculty startup funds. This study has been funded in whole or in part with federal funds from the National Cancer Institute, National Institutes of Health, under contract N01-CO-12400.; The content of this publication does not necessarily reflect the views or policies of the Department of Health and Human Services, nor does mention of trade names, commercial products, or organizations imply endorsement by the U. S. Government. NR 56 TC 16 Z9 16 U1 0 U2 1 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0022-538X J9 J VIROL JI J. Virol. PD DEC 15 PY 2008 VL 82 IS 24 BP 12164 EP 12171 DI 10.1128/JVI.01158-08 PG 8 WC Virology SC Virology GA 376DS UT WOS:000261164000017 PM 18829758 ER PT J AU Bukreyev, A Yang, LJ Fricke, J Cheng, L Ward, JM Murphy, BR Collins, PL AF Bukreyev, Alexander Yang, Lijuan Fricke, Jens Cheng, Lily Ward, Jerrold M. Murphy, Brian R. Collins, Peter L. TI The Secreted Form of Respiratory Syncytial Virus G Glycoprotein Helps the Virus Evade Antibody-Mediated Restriction of Replication by Acting as an Antigen Decoy and through Effects on Fc Receptor-Bearing Leukocytes SO JOURNAL OF VIROLOGY LA English DT Article ID RECOMBINANT VACCINIA VIRUS; CYSTEINE-RICH REGION; G-PROTEIN; INFLUENZA-VIRUS; INFECTED-CELLS; EBOLA-VIRUS; SOLUBLE GLYCOPROTEIN; ATTACHMENT PROTEIN; GENETIC DIVERSITY; COTTON RATS AB Respiratory syncytial virus (RSV) readily infects and reinfects during infancy and throughout life, despite maternal antibodies and immunity from prior infection and without the need for significant antigenic change. RSV has two neutralization antigens, the F and G virion glycoproteins. G is expressed in both membrane-bound (mG) and secreted (sG) forms. We investigated whether sG might act as a decoy for neutralizing antibodies by comparing the in vitro neutralization of wild-type (wt) RSV versus recombinant mG RSV expressing only mG. wt RSV indeed was less susceptible than mG RSV to monovalent G-specific and polyvalent RSV-specific antibodies, whereas susceptibility to F-specific antibodies was equivalent. This difference disappeared when the virus preparations were purified to remove sG. Thus, sG appears to function as a neutralization decoy. We evaluated this effect in vivo in mice by comparing the effects of passively transferred antibodies on the pulmonary replication of wt RSV versus mG RSV. Again, wt RSV was less sensitive than mG RSV to G-specific and RSV-specific antibodies; however, a similar difference was also observed with F-specific antibodies. This confirmed that sG helps wt RSV evade the antibody-dependent restriction of replication but indicated that in mice, it is not acting primarily as a decoy for G-specific antibodies, perhaps because sG is produced in insufficient quantities in this poorly permissive animal. Rather, we found that the greater sensitivity of mG versus wt RSV to the antiviral effect of passively transferred RSV antibodies required the presence of inflammatory cells in the lung and was Fc gamma receptor dependent. Thus, sG helps RSV escape the antibody-dependent restriction of replication via effects as an antigen decoy and as a modulator of leukocytes bearing Fc gamma receptors. C1 [Bukreyev, Alexander; Yang, Lijuan; Fricke, Jens; Murphy, Brian R.; Collins, Peter L.] NIAID, LID, NIH, Bethesda, MD 20892 USA. [Cheng, Lily; Ward, Jerrold M.] NIAID, Infect Dis Pathogenesis Sect, Comparat Med Branch, NIH, Bethesda, MD 20892 USA. RP Bukreyev, A (reprint author), NIAID, LID, NIH, 50 S Dr,Room 6505, Bethesda, MD 20892 USA. EM abukreyev@nih.gov FU NIAID FX This project was funded as part of the NIAID intramural program. NR 55 TC 61 Z9 65 U1 0 U2 3 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0022-538X J9 J VIROL JI J. Virol. PD DEC 15 PY 2008 VL 82 IS 24 BP 12191 EP 12204 DI 10.1128/JVI.01604-08 PG 14 WC Virology SC Virology GA 376DS UT WOS:000261164000020 PM 18842713 ER PT J AU Howard, AR Senkevich, TG Moss, B AF Howard, Amanda R. Senkevich, Tatiana G. Moss, Bernard TI Vaccinia Virus A26 and A27 Proteins Form a Stable Complex Tethered to Mature Virions by Association with the A17 Transmembrane Protein SO JOURNAL OF VIROLOGY LA English DT Article ID A-TYPE INCLUSION; INTRACELLULAR MOVEMENT; CELL-SURFACE; ESSENTIAL COMPONENT; MEMBRANE-PROTEIN; GENE; IDENTIFICATION; POLYPEPTIDES; MICROTUBULES; PARTICLES AB During vaccinia virus replication, mature virions (MVs) are wrapped with cellular membranes, transported to the periphery, and exported as extracellular virions (EVs) that mediate spread. The A26 protein is unusual in that it is present in MVs but not EVs. This distribution led to a proposal that A26 negatively regulates wrapping. A26 also has roles in the attachment of MVs to the cell surface and incorporation of MVs into proteinaceous A-type inclusions in some orthopoxvirus species. However, A26 lacks a transmembrane domain, and nothing is known regarding how it associates with the MV, regulates incorporation of the MV into inclusions, and possibly prevents EV formation. Here, we provide evidence that A26 forms a disulfide-bonded complex with A27 that is anchored to the MV through a noncovalent interaction with the A17 transmembrane protein. In the absence of A27, A26 was unstable, and only small amounts were detected. The interaction of A26 with A27 depended on a C-terminal segment of A26 with 45% amino acid identity to A27. Deletion of A26 failed to enhance EV formation by vaccinia virus, as had been predicted. Nevertheless, the interaction of A26 and A27 may have functional significance, since each is thought to mediate binding to cells through interaction with laminin and heparan sulfate, respectively. We also found that A26 formed a noncovalent complex with A25, a truncated form of the cowpox virus A-type inclusion matrix protein. The latter association suggests a mechanism for incorporation of virions into A-type inclusions in other orthopoxvirus strains. C1 [Howard, Amanda R.; Senkevich, Tatiana G.; Moss, Bernard] NIAID, Viral Dis Lab, NIH, Bethesda, MD 20892 USA. RP Moss, B (reprint author), NIAID, Viral Dis Lab, NIH, 33 N Dr,MSC 3210, Bethesda, MD 20892 USA. EM bmoss@nih.gov FU Division of Intramural Research; NIAID; NIH FX The research was supported by the Division of Intramural Research, NIAID, NIH. NR 38 TC 23 Z9 27 U1 0 U2 1 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0022-538X J9 J VIROL JI J. Virol. PD DEC 15 PY 2008 VL 82 IS 24 BP 12384 EP 12391 DI 10.1128/JVI.01524-08 PG 8 WC Virology SC Virology GA 376DS UT WOS:000261164000038 PM 18842719 ER PT J AU Yuste, E Bixby, J Lifson, J Sato, S Johnson, W Desrosiers, R AF Yuste, Eloisa Bixby, Jacqueline Lifson, Jeffrey Sato, Shuji Johnson, Welkin Desrosiers, Ronald TI Glycosylation of gp41 of Simian Immunodeficiency Virus Shields Epitopes That Can Be Targets for Neutralizing Antibodies SO JOURNAL OF VIROLOGY LA English DT Article ID N-LINKED GLYCANS; EXTRACELLULAR ENVELOPE GLYCOPROTEIN; TYPE-1 ENVELOPE; IN-VIVO; V3 LOOP; MACROPHAGE TROPISM; RESISTANCE; CD4; INFECTION; HIV-1 AB Human immunodeficiency virus type 1 and simian immunodeficiency virus possess three closely spaced, highly conserved sites for N-linked carbohydrate attachment in the extracellular domain of the transmembrane protein gp41. We infected rhesus monkeys with a variant of cloned SIVmac239 lacking the second and third sites or with a variant strain lacking all three of SIVmac239's glycosylation sites in gp41. For each mutation, asparagine (N) in the canonical N-X-S/T recognition sequence for carbohydrate attachment was changed to the structurally similar glutamine such that two nucleotide changes would be required for a reversion of the mutated codon. By 16 weeks, experimentally infected monkeys made antibodies that neutralized the mutant viruses to high titers. Such antibodies were not observed in monkeys infected with the parental virus. Thus, new specificities were revealed as a result of the carbohydrate attachment mutations, and antibodies of these specificities had neutralizing activity. Unlike monkeys infected with the parental virus, monkeys infected with the mutant viruses made antibodies that reacted with peptides corresponding to the sequences in this region. Furthermore, there was strong selective pressure for the emergence of variant sequences in this region during the course of infection. By analyzing the neutralization profiles of sequence variants, we were able to define three mutations (Q625R, K631N, and Q634H) in the region of the glycosylation site mutations that conferred resistance to neutralization by plasma from the monkeys infected with mutant virus. Based on the reactivity of antibodies to peptides in this region and the colocalization of neutralization escape mutations, we conclude that N-linked carbohydrates in the ectodomain of the transmembrane protein shield underlying epitopes that would otherwise be the direct targets of neutralizing antibodies. C1 [Yuste, Eloisa; Bixby, Jacqueline; Sato, Shuji; Johnson, Welkin; Desrosiers, Ronald] Harvard Univ, New England Primate Res Ctr, Sch Med, Dept Microbiol & Mol Genet, Southborough, MA 01772 USA. [Lifson, Jeffrey] NCI, Frederick Canc Res Facil, Frederick, MD USA. RP Desrosiers, R (reprint author), Harvard Univ, New England Primate Res Ctr, Sch Med, Dept Microbiol & Mol Genet, 1 Pine Hill Dr,Box 9102, Southborough, MA 01772 USA. EM ronald_desrosiers@hms.harvard.edu FU U. S. Public Health Service [AI025328, AI150421]; NEPRC [AI057039, RR00168]; National Cancer Institute, National Institutes of Health [N01-CO12400] FX This work was supported by U. S. Public Health Service grants AI025328 and AI150421 to R. D., AI057039 to W. J., and RR00168 to the NEPRC; by an award from the International AIDS Vaccine Initiative; and in part with federal funds from the National Cancer Institute, National Institutes of Health, under contract N01-CO12400. NR 39 TC 11 Z9 13 U1 0 U2 1 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0022-538X J9 J VIROL JI J. Virol. PD DEC 15 PY 2008 VL 82 IS 24 BP 12472 EP 12486 DI 10.1128/JVI.01382-08 PG 15 WC Virology SC Virology GA 376DS UT WOS:000261164000047 PM 18829751 ER PT J AU Day, PM Lowy, DR Schiller, JT AF Day, Patricia M. Lowy, Douglas R. Schiller, John T. TI Heparan Sulfate-Independent Cell Binding and Infection with Furin-Precleaved Papillomavirus Capsids SO JOURNAL OF VIROLOGY LA English DT Article ID PROPROTEIN CONVERTASES; HUMAN KERATINOCYTES; NEUTRALIZATION; EXPRESSION; CLEAVAGE; PROTEIN; L2; ACTIVATION; MECHANISMS; GENERATION AB Papillomavirus infection normally involves virion binding to cell surface heparan sulfate proteoglycans (HSPGs). However, we found that human papillomavirus type 16 pseudovirions efficiently bound and infected cells lacking HSPGs if their L2 capsid protein was precleaved by furin, a cellular protease required for infection. The inability of pseudovirions to efficiently bind and infect cultured primary keratinocytes was also overcome by furin precleavage, suggesting that the defect involves altered HSPG modification. We conclude that the primary function of HSPG binding is to enable cell surface furin cleavage of L2 and that binding to a distinct cell surface receptor(s) is a subsequent step of papillomavirus infection. C1 [Day, Patricia M.; Lowy, Douglas R.; Schiller, John T.] NCI, Cellular Oncol Lab, NIH, Bethesda, MD 20892 USA. RP Day, PM (reprint author), NCI, Cellular Oncol Lab, NIH, Bethesda, MD 20892 USA. EM pmd@nih.gov FU National Institutes of Health; National Cancer Institute; Center for Cancer Research FX This research was supported by the Intramural Research Program of the National Institutes of Health, National Cancer Institute, Center for Cancer Research. NR 27 TC 69 Z9 71 U1 0 U2 1 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0022-538X J9 J VIROL JI J. Virol. PD DEC 15 PY 2008 VL 82 IS 24 BP 12565 EP 12568 DI 10.1128/JVI.01631-08 PG 4 WC Virology SC Virology GA 376DS UT WOS:000261164000055 PM 18829767 ER PT J AU Wurster, AL Pazin, MJ AF Wurster, Andrea L. Pazin, Michael J. TI BRG1-Mediated Chromatin Remodeling Regulates Differentiation and Gene Expression of T Helper Cells SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Article ID TRANSCRIPTION FACTOR GATA-3; LOCUS-CONTROL REGION; ACTIVATED PROTEIN-KINASE; TH2 CELLS; HISTONE ACETYLATION; CYTOKINE GENES; CUTTING EDGE; SWI/SNF COMPLEX; BAF COMPLEX; PROMOTER AB During T helper cell differentiation, distinct programs of gene expression play a key role in defining the immune response to an environmental challenge. How chromatin remodeling events at the associated cytokine loci control differentiation is not known. We found that the ATP-dependent remodeling enzyme subunit BRG1 was required for T helper 2 (Th2) differentiation and Th2 cytokine transcription. BRG1 binding to cytokine genes was regulated by the extent of differentiation, the extent of activation, and cell fate. BRG1 was required for some features of the chromatin structure in target genes (DNase I hypersensitivity and histone acetylation), suggesting that BRG1 remodeling activity was directly responsible for changes in gene expression. NFAT and STAT6 activity were required for BRG1 recruitment to the Th2 locus control region, and STAT6 associated with BRG1 in a differentiation-inducible manner, suggesting direct recruitment of BRG1 to the bound loci. Together, these findings suggest BRG1 interprets differentiation signals and plays a causal role in gene regulation, chromatin structure, and cell fate. C1 [Wurster, Andrea L.; Pazin, Michael J.] NIA, Cellular & Mol Biol Lab, NIH, Baltimore, MD 21224 USA. RP Pazin, MJ (reprint author), NIA, Cellular & Mol Biol Lab, NIH, 251 Bayview Blvd, Baltimore, MD 21224 USA. EM pazinm@mail.nih.gov OI Pazin, Michael/0000-0002-7561-3640 FU National Institutes of Health; National Institute on Aging FX This research was supported by the Intramural Research Program of the National Institutes of Health, National Institute on Aging. NR 68 TC 38 Z9 42 U1 1 U2 3 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0270-7306 J9 MOL CELL BIOL JI Mol. Cell. Biol. PD DEC 15 PY 2008 VL 28 IS 24 BP 7274 EP 7285 DI 10.1128/MCB.00835-08 PG 12 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 376EO UT WOS:000261166900002 PM 18852284 ER PT J AU Galliher-Beckley, AJ Williams, JG Collins, JB Cidlowski, JA AF Galliher-Beckley, Amy Jo Williams, Jason Grant Collins, Jennifer Brady Cidlowski, John Anthony TI Glycogen Synthase Kinase 3 beta-Mediated Serine Phosphorylation of the Human Glucocorticoid Receptor Redirects Gene Expression Profiles SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Article ID TRANSCRIPTIONAL ACTIVATION; NUCLEAR RECEPTORS; CELL-SURVIVAL; TARGET GENES; PROTEIN; MECHANISMS; IDENTIFICATION; KINASE-3-BETA; INHIBITION; ISOFORMS AB Aberrant glycogen synthase kinase 3 beta (GSK-3 beta) activity is associated with the progression of several pathological conditions such as diabetes, Alzheimer's, and cancer. GSK-3 beta regulates cellular processes by directly phosphorylating metabolic enzymes and transcription factors. Here, we discovered a new target for GSK-3 beta phosphorylation: the human glucocorticoid receptor (GR). Glucocorticoid signaling is essential for life and regulates diverse biological functions from cell growth to metabolism to apoptosis. Specifically, we found hormone-dependent GR phosphorylation on serine 404 by GSK-3 beta. Cells expressing a GR that is incapable of GSK-3 beta phosphorylation had a redirection of the global transcriptional response to hormone, including the activation of additional signaling pathways, in part due to the altered ability of unphosphorylatable GR to recruit transcriptional cofactors CBP/p300 and the p65 (RelA) subunit of NF-kappa B. Furthermore, GSK-3 beta-mediated GR phosphorylation inhibited glucocorticoid-dependent NF-kappa B transrepression and attenuated the glucocorticoid-dependent cell death of osteoblasts. Collectively, our results describe a novel convergence point of the GSK-3 beta and the GR pathways, resulting in altered hormone-regulated signaling. Our results also provide a mechanism by which GSK-3 beta activity can dictate how cells will ultimately respond to glucocorticoids. C1 [Galliher-Beckley, Amy Jo; Cidlowski, John Anthony] NIEHS, Mol Endocrinol Grp, Lab Signal Transduct, NIH,Dept Hlth & Human Serv, Res Triangle Pk, NC 27709 USA. [Williams, Jason Grant] NIEHS, Struct Biol Lab, NIH, Dept Hlth & Human Serv, Res Triangle Pk, NC 27709 USA. [Collins, Jennifer Brady] NIEHS, Microarray Ctr, NIH, Dept Hlth & Human Serv, Res Triangle Pk, NC 27709 USA. RP Cidlowski, JA (reprint author), NIEHS, Mol Endocrinol Grp, Lab Signal Transduct, NIH,Dept Hlth & Human Serv, POB 12233,111 TW Alexander Dr, Res Triangle Pk, NC 27709 USA. EM cidlows1@niehs.nih.gov FU NIH National Institute of Environmental Health Sciences [Z01E5090057-12] FX This research was supported by the Intramural Research Program of the NIH National Institute of Environmental Health Sciences (Z01E5090057-12). NR 49 TC 61 Z9 61 U1 0 U2 2 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0270-7306 J9 MOL CELL BIOL JI Mol. Cell. Biol. PD DEC 15 PY 2008 VL 28 IS 24 BP 7309 EP 7322 DI 10.1128/MCB.00808-08 PG 14 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 376EO UT WOS:000261166900005 PM 18838540 ER PT J AU Kotekar, AS Weissman, JD Gegonne, A Cohen, H Singer, DS AF Kotekar, Aparna S. Weissman, Jocelyn D. Gegonne, Anne Cohen, Helit Singer, Dinah S. TI Histone Modifications, but Not Nucleosomal Positioning, Correlate with Major Histocompatibility Complex Class I Promoter Activity in Different Tissues In Vivo SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Article ID NF-KAPPA-B; STIMULATED RESPONSE ELEMENT; GENE-EXPRESSION; NUCLEAR-FACTOR; GENOME-WIDE; TRANSCRIPTIONAL COACTIVATOR; PREFERENTIAL ACCESSIBILITY; SACCHAROMYCES-CEREVISIAE; REGULATORY REGIONS; PHO5 PROMOTER AB To examine the role of chromatin in transcriptional regulation of the major histocompatibility complex (MHC) class I gene, we determined nucleosome occupancy and positioning, histone modifications, and H2A.Z occupancy across its regulatory region in murine tissues that have widely different expression levels. Surprisingly, nucleosome occupancy and positioning were indistinguishable between the spleen, kidney, and brain. In all three tissues, the 200 bp upstream of the transcription start site had low nucleosome occupancy. In contrast, nuclease hypersensitivity, histone modifications, and H2A.Z occupancy showed tissue-specific differences. Thus, tissue-specific differences in MHC class I transcription correlate with histone modifications and not nucleosomal organization. Further, activation of class I transcription by gamma interferon or its inhibition by alpha-amanitin did not alter nucleosome occupancy, positioning, nuclease hypersensitivity, histone modifications, or H2A.Z occupancy in any of the tissues examined. Thus, chromatin remodeling was not required to dynamically modulate transcriptional levels. These findings suggest that the MHC class I promoter remains poised and accessible to rapidly respond to infection and environmental cues. C1 [Kotekar, Aparna S.; Weissman, Jocelyn D.; Gegonne, Anne; Cohen, Helit; Singer, Dinah S.] NCI, Mol Regulat Sect, Expt Immunol Branch, NIH, Bethesda, MD 20892 USA. RP Singer, DS (reprint author), NCI, Mol Regulat Sect, Expt Immunol Branch, NIH, Bldg 10,Rm 4B-36, Bethesda, MD 20892 USA. EM dinah.singer@nih.gov FU NIH; National Cancer Institute; Center for Cancer Research FX This research was supported by the Intramural Research Program of the NIH, National Cancer Institute, Center for Cancer Research. NR 65 TC 9 Z9 9 U1 0 U2 1 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0270-7306 J9 MOL CELL BIOL JI Mol. Cell. Biol. PD DEC 15 PY 2008 VL 28 IS 24 BP 7323 EP 7336 DI 10.1128/MCB.00889-08 PG 14 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 376EO UT WOS:000261166900006 PM 18809568 ER PT J AU Pilon, AM Arcasoy, MO Dressman, HK Vayda, SE Maksimova, YD Sangerman, JI Gallagher, PG Bodine, DM AF Pilon, Andre M. Arcasoy, Murat O. Dressman, Holly K. Vayda, Serena E. Maksimova, Yelena D. Sangerman, Jose I. Gallagher, Patrick G. Bodine, David M. TI Failure of Terminal Erythroid Differentiation in EKLF-Deficient Mice Is Associated with Cell Cycle Perturbation and Reduced Expression of E2F2 SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Article ID KRUPPEL-LIKE FACTOR; CHROMATIN REMODELING COMPLEX; TRANSCRIPTION FACTOR EKLF; BETA-GLOBIN PROMOTER; LOCUS-CONTROL REGION; FETAL HEMOGLOBIN; S-PHASE; GENE; ERYTHROPOIESIS; MATURATION AB Erythroid Kruppel-like factor (EKLF) is a Kruppel-like transcription factor identified as a transcriptional activator and chromatin modifier in erythroid cells. EKLF-deficient (Eklf(-/-)) mice die at day 14.5 of gestation from severe anemia. In this study, we demonstrate that early progenitor cells fail to undergo terminal erythroid differentiation in Eklf(-/-) embryos. To discover potential EKLF target genes responsible for the failure of erythropoiesis, transcriptional profiling was performed with RNA from wild-type and Eklf(-/-) early erythroid progenitor cells. These analyses identified significant perturbation of a network of genes involved in cell cycle regulation, with the critical regulator of the cell cycle, E2f2, at a hub. E2f2 mRNA and protein levels were markedly decreased in Eklf(-/-) early erythroid progenitor cells, which showed a delay in the G(1)-to-S-phase transition. Chromatin immunoprecipitation analysis demonstrated EKLF occupancy at the proximal E2f2 promoter in vivo. Consistent with the role of EKLF as a chromatin modifier, EKLF binding sites in the E2f2 promoter were located in a region of EKLF-dependent DNase I sensitivity in early erythroid progenitor cells. We propose a model in which EKLF-dependent activation and modification of the E2f2 locus is required for cell cycle progression preceding terminal erythroid differentiation. C1 [Pilon, Andre M.; Vayda, Serena E.; Bodine, David M.] NHGRI, Hematopoiesis Sect, Genet & Mol Biol Branch, NIH, Bethesda, MD 20892 USA. [Pilon, Andre M.] George Washington Univ, Med Ctr, Dept Biochem & Mol Biol, Washington, DC 20037 USA. [Arcasoy, Murat O.] Duke Univ, Med Ctr, Durham, NC 27710 USA. [Dressman, Holly K.] CIEMAS, Duke Inst Genome Sci & Policy 2177B, Durham, NC 27708 USA. [Maksimova, Yelena D.; Sangerman, Jose I.; Gallagher, Patrick G.] Yale Univ, Sch Med, Dept Pediat, New Haven, CT 06520 USA. RP Bodine, DM (reprint author), NHGRI, Hematopoiesis Sect, Genet & Mol Biol Branch, NIH, 49 Convent Dr,MSC-4442,Bldg 49,Room 4A04, Bethesda, MD 20892 USA. EM tedyaz@mail.nih.gov FU NHGRI [RO1 DK62039, RO1 HL65448, T32 HD07094] FX This study was supported by grants RO1 DK62039 and RO1 HL65448 (P.G.G.) and T32 HD07094 (J.I.S.) and by NHGRI intramural funds. NR 43 TC 54 Z9 54 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0270-7306 J9 MOL CELL BIOL JI Mol. Cell. Biol. PD DEC 15 PY 2008 VL 28 IS 24 BP 7394 EP 7401 DI 10.1128/MCB.01087-08 PG 8 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 376EO UT WOS:000261166900012 PM 18852285 ER PT J AU Zeuner, KE Peller, M Knutzen, A Hallett, M Deuschl, G Siebner, HR AF Zeuner, Kirsten E. Peller, Martin Knutzen, Arne Hallett, Mark Deuschl, Guenther Siebner, Hartwig R. TI Motor Re-Training Does Not Need to Be Task Specific to Improve Writer's Cramp SO MOVEMENT DISORDERS LA English DT Article DE focal hand dystonia; writer's cramp; kinematic analysis; training; writing; immobilization ID FOCAL HAND DYSTONIA; 1-YEAR FOLLOW-UP; BOTULINUM TOXIN; PATHOPHYSIOLOGY; PERFORMANCE AB Previous studies showed a beneficial effect of motor re-training in task-specific hand dystonia. Here we examined whether re-training needs to specifically focus on the task affected by dystonia. 21 patients with writer's cramp were randomly assigned to two types of re-training: One group of patients trained drawing and writing movements using a pen attached to the bottom of a finger splint. The second group used therapeutic putty to train finger movements without exercises of drawing and writing movements. Training lasted for 8 weeks. Before re-training, affected hand and forearm were immobilized for 4 weeks to facilitate the responsiveness to re-training. Dystonia was assessed during handwriting using the Writer's Cramp Rating Scale. Although no clinical improvement was observed immediately after immobilization, 8 weeks of re-training improved task-specific dystonia relative to baseline (P = 0.005). Both training modalities were equally effective. More severely affected patients benefited most. There was no correlation between disease duration and the individual treatment response. Retraining also improved hand function as indexed by the Ann Dystonia Disability Scale (P = 0.008). Kinematic handwriting analysis showed that re-training lowered vertical force level and enhanced the fluency of handwriting. We conclude that re-training does not need to specifically focus on the task affected by dystonia to be clinically effective. (c) 2008 Movement Disorder Society C1 [Zeuner, Kirsten E.] Univ Kiel, Dept Neurol, Neurozentrum, D-24105 Kiel, Germany. [Siebner, Hartwig R.] NeuroImageNord Kiel Hamburg Lubeck, Lubeck, Germany. [Hallett, Mark] NINDS, Human Motor Control Sect, Med Neurol Branch, NIH, Bethesda, MD 20892 USA. RP Zeuner, KE (reprint author), Univ Kiel, Dept Neurol, Neurozentrum, Schittenhelmstr 10, D-24105 Kiel, Germany. EM k.zeuner@neurologie.uni-kiel.de RI Deuschl, Gunther/A-7986-2010; Siebner, Hartwig/G-4052-2016 FU Deutsche Forschungsgemeinschaft [DE 438/7-1, 7-2]; Federal Ministry of Education and Research [01 GO 0511] FX This work has been supported by the Deutsche Forschungsgemeinschaft to G. Deuschl and H. Siebner (grant DE 438/7-1 and 7-2). H.R. Siebner was supported by a structural grant sponsored by the Federal Ministry of Education and Research to Neuro-ImageNord (grant 01 GO 0511). We greatly appreciate the patients and normal volunteers for participating in this study. We would like to thank Dirk Dressler, MD. Department of Neurology at the University of Rostock, Alexander Munchau, MD. Department of Neurology at, the University of Hamburg, Lars Timmermann, MD and Markus Butz, PhD, Department of Neurology, University of Dusseldorf for referring patients to us. The corresponding author had full access to all of the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis. NR 26 TC 22 Z9 22 U1 1 U2 7 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 2008 VL 23 IS 16 BP 2319 EP 2327 DI 10.1002/mds.22222 PG 9 WC Clinical Neurology SC Neurosciences & Neurology GA 391PG UT WOS:000262244600005 PM 18816801 ER PT J AU Daly, JW Garraffo, HM Spande, TF Yeh, HJC Peltzer, PM Cacivio, PM Baldo, JD Faivovich, J AF Daly, John W. Garraffo, H. Martin Spande, Thomas F. Yeh, Herman J. C. Peltzer, Paola M. Cacivio, Pedro M. Baldo, J. Diego Faivovich, Julian TI Indolizidine 239Q and quinolizidine 275I. Major alkaloids in two Argentinian bufonid toads (Melanophryniscus) SO TOXICON LA English DT Article DE Alkaloids; Ants; Bufonidae; Dietary arthropods; Mass spectrometry; Mites ID DART FROGS DENDROBATIDAE; RED-BELLIED TOADS; POISON FROGS; PAPIERCHROMATOGRAPHISCHE PRUFUNG; DIET SPECIALIZATION; ARTHROPOD SOURCE; AMPHIBIAN SKIN; COSTA-RICA; TETRODOTOXIN; BUFADIENOLIDES AB Alkaloid profiles in skin of poison frogs/toads (Dendrobatidae, Mantellidae, Bufonidae, and Myobatrachidae) are highly dependent on diet and hence on the nature of habitat. Extracts of the two species of toads (Melanophryniscus kiappenbachi and Melanophryniscus cupreuscapularis) from similar habitats in the Corrientes/Chaco Provinces of Argentina have similar profiles of alkaloids, which differ considerably in profiles from other Metanophryniscus species from Brazil, Uruguay and Argentina. Structures of two major alkaloids 239Q (1) and 275I (2) were determined by mass, FTIR, and NMR spectral analysis as 5Z9Z-3-(1-hydroxybutyl)-5-propylindolizidine and 6Z,10E-4,6-di(pent-4-enyl) quinolizidine, respectively. A third alkaloid, 249F (3), is postulated to be a homopumiliotoxin with an unprecedented conjugated exocyclic diene moiety. (C) 2008 Elsevier Ltd. All rights reserved. C1 [Daly, John W.; Garraffo, H. Martin; Spande, Thomas F.; Yeh, Herman J. C.] NIDDKD, Bioorgan Chem Lab, NIH, DHHS, Bethesda, MD 20892 USA. [Peltzer, Paola M.] ESS FBCB UNL, Fac Bioquim & Ciencias Biol, CONICET, RA-3000 Santa Fe, Argentina. [Baldo, J. Diego] Univ Nacl Misiones, CONICET, Lab Genet Evolut, Fac Ciencias Exactas Quim & Nat,Dept Genet, Posadas, Misiones, Argentina. [Cacivio, Pedro M.] Consejo Nacl Invest Cient & Tecn, Museo Argentina Ciencias Nat, Div Herpetol, RA-1405 Buenos Aires, DF, Argentina. [Faivovich, Julian] Univ Estadual Paulista, Inst Biociencias, Dept Zool, BR-13506900 Sao Paulo, Brazil. RP Garraffo, HM (reprint author), NIDDKD, Bioorgan Chem Lab, NIH, DHHS, 9000 Rockville Pike,Bldg 8,Room 1A24, Bethesda, MD 20892 USA. EM garraffo@helix.nih.gov OI Baldo, Diego/0000-0003-2382-0872 FU NIDDK; PMP; JDB; CONICET (Consejo Nacional de Investigaciones Cientificas y Tecnicas); PICT (Proyecto de Investigacion Cientifica y Tecnologica) [2006 223]; FAPESP (Fundaco de Amparo a Pesquisa do Estado de Sao Paulo) [2005/56756-0, 2006/562088-5] FX We thank Ralph Saporito for valuable suggestions and references. Work at NIH was supported by intramural funds of NIDDK. PMP, JDB, and JF thank Rafael C. Lajmanovich, CONICET (Consejo Nacional de Investigaciones Cientificas y Tecnicas) and PICT (Proyecto de Investigacion Cientifica y Tecnologica) 2006 223. JF thanks FAPESP (Fundaco de Amparo a Pesquisa do Estado de Sao Paulo) processes 2005/56756-0 and 2006/562088-5. NR 64 TC 26 Z9 26 U1 1 U2 8 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 2008 VL 52 IS 8 BP 858 EP 870 DI 10.1016/j.toxicon.2008.08.016 PG 13 WC Pharmacology & Pharmacy; Toxicology SC Pharmacology & Pharmacy; Toxicology GA 388XN UT WOS:000262053700005 PM 18848574 ER PT J AU Aldhous, P Gahl, W AF Aldhous, Peter Gahl, William TI Dr House's caring alter ego SO NEW SCIENTIST LA English DT Editorial Material C1 [Gahl, William] US Natl Human Genome Res Inst, Bethesda, MD USA. [Gahl, William] NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU REED BUSINESS INFORMATION LTD PI SUTTON PA QUADRANT HOUSE THE QUADRANT, SUTTON SM2 5AS, SURREY, ENGLAND SN 0262-4079 J9 NEW SCI JI New Sci. PD DEC 13 PY 2008 VL 200 IS 2686 BP 44 EP 45 DI 10.1016/S0262-4079(08)63163-2 PG 2 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 391BQ UT WOS:000262208200032 ER PT J AU Robbiani, DF Bothmer, A Callen, E Reina-San-Martin, B Dorsett, Y Difilippantonio, S Bolland, DJ Chen, HT Corcoran, AE Nussenzweig, A Nussenzweig, MC AF Robbiani, Davide F. Bothmer, Anne Callen, Elsa Reina-San-Martin, Bernardo Dorsett, Yair Difilippantonio, Simone Bolland, Daniel J. Chen, Hua Tang Corcoran, Anne E. Nussenzweig, Andre Nussenzweig, Michel C. TI AID Is Required for the Chromosomal Breaks in c-myc that Lead to c-myc/IgH Translocations SO CELL LA English DT Article ID CLASS-SWITCH RECOMBINATION; SINGLE-STRANDED-DNA; CYTIDINE DEAMINASE AID; HEAVY-CHAIN LOCUS; CENTER B-CELLS; SOMATIC HYPERMUTATION; BURKITT-LYMPHOMA; IN-VIVO; ANTIBODY DIVERSIFICATION; MURINE PLASMACYTOMAS AB Chromosomal translocation requires formation of paired double-strand DNA breaks (DSBs) on heterologous chromosomes. One of the most well characterized oncogenic translocations juxtaposes c-myc and the immunoglobulin heavy-chain locus (IgH) and is found in Burkitt's lymphomas in humans and plasmacytomas in mice. DNA breaks in IgH leading to c-myc/IgH translocations are created by activation-induced cytidine deaminase ( AID) during antibody class switch recombination or somatic hypermutation. However, the source of DNA breaks at c-myc is not known. Here, we provide evidence for the c-myc promoter region being required in targeting AID-mediated DNA damage to produce DSBs in c-myc that lead to c-myc/IgH translocations in primary B lymphocytes. Thus, in addition to producing somatic mutations and DNA breaks in antibody genes, AID is also responsible for the DNA lesions in oncogenes that are required for their translocation. C1 [Robbiani, Davide F.; Bothmer, Anne; Reina-San-Martin, Bernardo; Dorsett, Yair; Nussenzweig, Michel C.] Rockefeller Univ, Lab Mol Immunol, New York, NY 10065 USA. [Nussenzweig, Michel C.] Rockefeller Univ, Howard Hughes Med Inst, New York, NY 10065 USA. [Callen, Elsa; Difilippantonio, Simone; Chen, Hua Tang; Nussenzweig, Andre] NCI, NIH, Expt Immunol Branch, Bethesda, MD 20892 USA. [Bolland, Daniel J.; Corcoran, Anne E.] Babraham Inst, Lab Chromatin & Gene Express, Cambridge CB22 3AT, England. RP Nussenzweig, MC (reprint author), Rockefeller Univ, Lab Mol Immunol, New York, NY 10065 USA. EM nussen@mail.rockefeller.edu RI Reina-San-Martin, Bernardo/I-9484-2016 OI Reina-San-Martin, Bernardo/0000-0003-2083-6166 FU NIH; National Cancer Institute; Center for Cancer Research; Leukemia and Lymphoma Society; Howard Hughes Medical Institute Investigator FX All members of the Nussenzweig lab for discussions. Dr. Barry Stoddard ( Fred Hutchinson Cancer Research Center, Seattle) for suggestions on catalytically inactive I-SceI*. The Rockefeller University Gene Targeting Facility, Klara Velinzon, and Tamara Shengelia for FACSorting, Matthias Muellenbeck and Nancy Wong for technical assistance, and David Bosque and Tom Eisenreich for help in managing the mouse colonies. The work was supported in part by NIH grants to M. C. N. The A. N. lab was supported by the Intramural Research Program of the NIH, National Cancer Institute, Center for Cancer Research. D. F. R. is a Fellow of the Leukemia and Lymphoma Society, and M. C. N. is a Howard Hughes Medical Institute Investigator. NR 77 TC 222 Z9 227 U1 1 U2 12 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 0092-8674 J9 CELL JI Cell PD DEC 12 PY 2008 VL 135 IS 6 BP 1028 EP 1038 DI 10.1016/j.cell.2008.09.062 PG 11 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 382ZB UT WOS:000261642800019 PM 19070574 ER PT J AU Kachirskaia, I Shi, XB Yamaguchi, H Tanoue, K Wen, H Wang, EW Appella, E Gozani, O AF Kachirskaia, Ioulia Shi, Xiaobing Yamaguchi, Hiroshi Tanoue, Kan Wen, Hong Wang, Evelyn W. Appella, Ettore Gozani, Or TI Role for 53BP1 Tudor Domain Recognition of p53 Dimethylated at Lysine 382 in DNA Damage Signaling SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID HISTONE H4; METHYLATION; METHYLTRANSFERASE; REPRESSION; PR-SET7; BREAKS; SET8 AB Modification of histone proteins by lysine methylation is a principal chromatin regulatory mechanism (Shi, Y., and Whet-stine, J. R. (2007) Mol. Cell 25, 1-14). Recently, lysine methylation has been shown also to play a role in regulating non-histone proteins, including the tumor suppressor protein p53 (Huang, J., and Berger, S. L. (2008) Curr. Opin. Genet. Dev. 18, 152-158). Here, we identify a novel p53 species that is dimethylated at lysine 382 (p53K382me2) and show that the tandem Tudor domain of the DNA damage response mediator 53BP1 acts as an "effector" for this mark. We demonstrate that the 53BP1 tandem Tudor domain recognizes p53K382me2 with a selectivity relative to several other protein lysine methylation sites and saturation states. p53K382me2 levels increase with DNA damage, and recognition of this modification by 53BP1 facilitates an interaction between p53 and 53BP1. The generation of p53K382me2 promotes the accumulation of p53 protein that occurs upon DNA damage, and this increase in p53 levels requires 53BP1. Taken together, our study identifies a novel p53 modification, demonstrates a new effector function for the 53BP1 tandem Tudor domain, and provides insight into how DNA damage signals are transduced to stabilize p53. C1 [Kachirskaia, Ioulia; Shi, Xiaobing; Gozani, Or] Stanford Univ, Dept Biol, Stanford, CA 94305 USA. [Yamaguchi, Hiroshi; Tanoue, Kan; Appella, Ettore] NCI, Cell Biol Lab, NIH, Bethesda, MD 20892 USA. [Wen, Hong; Wang, Evelyn W.] Stanford Univ, Sch Med, Dept Pathol, Stanford, CA 94305 USA. RP Gozani, O (reprint author), Stanford Univ, Dept Biol, Stanford, CA 94305 USA. EM ogozani@stanford.edu FU National Institutes of Health [GM079641] FX This work was supported, in whole or in part, by National Institutes of Health Grant GM079641 (to O.G.) and the Intramural Research Program of the National Institutes of Health (to E. A. and H. Y.). The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked "advertisement" in accordance with 18 U. S. C. Section 1734 solely to indicate this fact. NR 20 TC 47 Z9 50 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 12 PY 2008 VL 283 IS 50 BP 34660 EP 34666 DI 10.1074/jbc.M806020200 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 380MF UT WOS:000261469100021 PM 18840612 ER PT J AU Burd, CJ Kinyamu, HK Miller, FW Archer, TK AF Burd, Craig J. Kinyamu, H. Karimi Miller, Frederick W. Archer, Trevor K. TI UV Radiation Regulates Mi-2 through Protein Translation and Stability SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID HISTONE DEACETYLASE; REMODELING COMPLEX; P53 TRANSLATION; MUSCLE DISEASE; BREAST-CANCER; CHROMATIN; DERMATOMYOSITIS; AUTOANTIBODIES; EXPRESSION; MYOSITIS AB Dermatomyositis (DM) is an autoimmune disease, which is often accompanied by the development of disease-specific autoantibodies directed against the SNF2-superfamily helicase, Mi-2. Recent evidence suggests that ultraviolet radiation exposure may be an important risk factor for the development of not only the disease but also specific autoimmunity against Mi-2. Consequently, we investigated the effects of ultraviolet radiation on Mi-2 protein expression. We observed an increase in protein levels upon ultraviolet radiation exposure in cell culture systems. These changes in expression occur quite rapidly, are maximized just 1 h following exposure, and are unique to Mi-2 when compared with other members of the NuRD complex. Changes in protein levels are not mediated through transcriptional mechanisms. Treatment results in a more efficiently translated message through regulatory elements in the 5'-UTR region of the transcript. Investigation into protein half-life further demonstrated increased stability of Mi-2 following UV exposure. Taken together, we describe a system by which Mi-2 protein expression can be quickly increased following UV exposure and then maintained up to 16 h later. These data provide a novel regulation of an important transcriptional regulator and provide insight into the possible mechanisms of the development of DM and associated autoantibodies. C1 [Burd, Craig J.; Kinyamu, H. Karimi; Archer, Trevor K.] NIEHS, Mol Carcinogenesis Lab, NIH, Res Triangle Pk, NC 27709 USA. [Miller, Frederick W.] NIEHS, Environm Autoimmunity Grp, Off Clin Res, NIH, Res Triangle Pk, NC 27709 USA. RP Archer, TK (reprint author), NIEHS, Mol Carcinogenesis Lab, NIH, MD D4-01,POB 12233, Res Triangle Pk, NC 27709 USA. EM archer1@niehs.nih.gov OI Miller, Frederick/0000-0003-2831-9593; Burd, Craig/0000-0002-6899-6751 FU Intramural Research Program of the NIEHS [Z01 ES071006-09]; National Institutes of Health FX This work was supported, in whole or in part, by Program Grant Z01 ES071006-09 in the Intramural Research Program of the NIEHS, National Institutes of Health. The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact. NR 33 TC 23 Z9 23 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 12 PY 2008 VL 283 IS 50 BP 34976 EP 34982 DI 10.1074/jbc.M805383200 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 380MF UT WOS:000261469100054 PM 18922793 ER PT J AU Sauna, ZE Bohn, SS Rutledge, R Dougherty, MP Cronin, S May, L Xia, D Ambudkar, SV Golin, J AF Sauna, Zuben E. Bohn, Sherry Supernavage Rutledge, Robert Dougherty, Michael P. Cronin, Susan May, Leopold Xia, Di Ambudkar, Suresh V. Golin, John TI Mutations Define Cross-talk between the N-terminal Nucleotide-binding Domain and Transmembrane Helix-2 of the Yeast Multidrug Transporter Pdr5 POSSIBLE CONSERVATION OF A SIGNALING INTERFACE FOR COUPLING ATP HYDROLYSIS TO DRUG TRANSPORT SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID CASSETTE ABC TRANSPORTER; SACCHAROMYCES-CEREVISIAE; CANDIDA-ALBICANS; P-GLYCOPROTEIN; ENCODING GENE; RESISTANCE; PROTEIN; EFFLUX; MECHANISM; CDR1P AB The yeast Pdr5 multidrug transporter is an important member of the ATP-binding cassette superfamily of proteins. We describe a novel mutation (S558Y) in transmembrane helix 2 of Pdr5 identified in a screen for suppressors that eliminated Pdr5-mediated cycloheximide hyper-resistance. Nucleotides as well as transport substrates bind to the mutant Pdr5 with an affinity comparable with that for wild-type Pdr5. Wild-type and mutant Pdr5s show ATPase activity with comparable K(m(ATP)) values. Nonetheless, drug sensitivity is equivalent in the mutant pdr5 and the pdr5 deletion. Finally, the transport substrate clotrimazole, which is a noncompetitive inhibitor of Pdr5 ATPase activity, has a minimal effect on ATP hydrolysis by the S558Y mutant. These results suggest that the drug sensitivity of the mutant Pdr5 is attributable to the uncoupling of NTPase activity and transport. We screened for amino acid alterations in the nucleotide-binding domains that would reverse the phenotypic effect of the S558Y mutation. A second-site mutation, N242K, located between the Walker A and signature motifs of the N-terminal nucleotide-binding domain, restores significant function. This region of the nucleotide-binding domain interacts with the transmembrane domains via the intracellular loop-1 (which connects transmembrane helices 2 and 3) in the crystal structure of Sav1866, a bacterial ATP-binding cassette drug transporter. These structural studies are supported by biochemical and genetic evidence presented here that interactions between transmembrane helix 2 and the nucleotide-binding domain, via the intracellular loop-1, may define at least part of the translocation pathway for coupling ATP hydrolysis to drug transport. C1 [Bohn, Sherry Supernavage; Dougherty, Michael P.; Golin, John] Catholic Univ Amer, Dept Biol, Washington, DC 20064 USA. [May, Leopold] Catholic Univ Amer, Dept Chem, Washington, DC 20064 USA. [Sauna, Zuben E.; Rutledge, Robert; Xia, Di; Ambudkar, Suresh V.] NCI, Cell Biol Lab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. [Cronin, Susan] Immaculata Univ, Dept Biol, Immaculata, PA 19345 USA. RP Golin, J (reprint author), Catholic Univ Amer, Dept Biol, McCort Ward Bldg 103, Washington, DC 20064 USA. EM golin@cua.edu FU National Institutes of Health (Intramural Research Program, Center for Cancer Research, NCI); National Institutes of Health [GM07721] FX Supported by National Institutes of Health Grant GM07721. NR 36 TC 37 Z9 37 U1 0 U2 4 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD DEC 12 PY 2008 VL 283 IS 50 BP 35010 EP 35022 DI 10.1074/jbc.M806446200 PG 13 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 380MF UT WOS:000261469100058 PM 18842589 ER PT J AU Choi, E Han, C Park, I Lee, B Jin, S Choi, H Kim, DH Park, ZY Eddy, EM Cho, C AF Choi, Eunyoung Han, Cecil Park, Inju Lee, Boyeon Jin, Sora Choi, Heejin Kim, Do Han Park, Zee Yong Eddy, Edward M. Cho, Chunghee TI A Novel Germ Cell-specific Protein, SHIP1, Forms a Complex with Chromatin Remodeling Activity during Spermatogenesis SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID HISTONE-DEACETYLASES; MOUSE SPERMATOGENESIS; VALPROIC ACID; CO-REPRESSOR; SANT DOMAIN; N-COR; MEIOSIS; HSP70-2; GENES; IDENTIFICATION AB To determine the mechanisms of spermatogenesis, it is essential to identify and characterize germ cell-specific genes. Here we describe a protein encoded by a novel germ cell-specific gene, Mm. 290718/ZFP541, identified from the mouse spermatocyte UniGene library. Theprotein contains specific motifs and domains potentially involved in DNA binding and chromatin reorganization. An antibody against Mm. 290718/ZFP541 revealed the existence of the protein in testicular spermatogenic cells (159 kDa) but not testicular and mature sperm. Immunostaining analysis of cells at various stages of spermatogenesis consistently showed that the protein is present in spermatocytes and round spermatids only. Transfection assays and immunofluorescence studies indicate that the protein is localized specifically in the nucleus. Proteomic analyses performed to explore the functional characteristics of Mm. 290718/ZFP541 showed that the protein forms a unique complex. Other major components of the complex included histone deacetylase 1 (HDAC1) and heat-shock protein A2. Disappearance of Mm. 290718/ZFP541 was highly correlated with hyperacetylation in spermatids during spermatogenesis, and specific domains of the protein were involved in the regulation of interactions and nuclear localization of HDAC1. Furthermore, we found that premature hyperacetylation, induced by an HDAC inhibitor, is associated with an alteration in the integrity of Mm. 290718/ZFP541 in spermatogenic cells. Our results collectively suggest that the Mm. 290718/ZFP541 complex is implicated in chromatin remodeling during spermatogenesis, and we provide further information on the previously unknown molecular mechanism. Consequently, we re-designate Mm. 290718/ZFP541 as "SHIP1" representing spermatogenic cell HDAC-interacting protein 1. C1 [Choi, Eunyoung; Han, Cecil; Park, Inju; Lee, Boyeon; Jin, Sora; Choi, Heejin; Kim, Do Han; Park, Zee Yong; Cho, Chunghee] Gwangju Inst Sci & Technol, Dept Life Sci, Kwangju 500712, South Korea. [Choi, Eunyoung; Han, Cecil; Park, Inju; Lee, Boyeon; Jin, Sora; Choi, Heejin; Kim, Do Han; Park, Zee Yong; Cho, Chunghee] Gwangju Inst Sci & Technol, Res Ctr Biomol Nanotechnol, Kwangju 500712, South Korea. [Eddy, Edward M.] NIEHS, Gamete Biol Sect, Reprod & Dev Toxicol Lab, NIH, Res Triangle Pk, NC 27709 USA. RP Cho, C (reprint author), Gwangju Inst Sci & Technol, Dept Life Sci, Kwangju 500712, South Korea. EM choch@gist.ac.kr FU National Institutes of Health [ZO1 ES070077]; Korea Science and Engineering Foundation [RO1-2007-000-20116]; Korean Systems Biology Research Grant [M10503010001-06N0301-00110]; GIST Systems Biology Infrastructure Establishment FX This work was supported, in whole or in part, by National Institutes of Health Grant ZO1 ES070077 ( Project 1, Intramural Research Program, NIEHS). This work was also supported by the Korea Science and Engineering Foundation Grant RO1-2007-000-20116, Korean Systems Biology Research Grant M10503010001-06N0301-00110, and GIST Systems Biology Infrastructure Establishment grant. The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked "advertisement" in accordance with 18 U. S. C. Section 1734 solely to indicate this fact. NR 36 TC 19 Z9 23 U1 1 U2 4 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 12 PY 2008 VL 283 IS 50 BP 35283 EP 35294 DI 10.1074/jbc.M805590200 PG 12 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 380MF UT WOS:000261469100084 PM 18849567 ER PT J AU Zhou, Z Feng, HQ Ghirlando, R Bai, YW AF Zhou, Zheng Feng, Hanqiao Ghirlando, Rodolfo Bai, Yawen TI The High-Resolution NMR Structure of the Early Folding Intermediate of the Thermus thermophilus Ribonuclease H SO JOURNAL OF MOLECULAR BIOLOGY LA English DT Article DE protein folding intermediate; protein folding; NMR structure; hydrogen exchange; protein engineering ID STATE HYDROGEN-EXCHANGE; 2-STATE PROTEINS; NATIVE-STATE; DENATURED STATE; RATE PREDICTION; CONTACT ORDER; CHAIN-LENGTH; PATHWAY; EQUILIBRIUM; MECHANISM AB Elucidation of the high-resolution structures of folding intermediates is a necessary but difficult step toward the ultimate understanding of the mechanism of protein folding. Here, using hydrogen-exchange-directed protein engineering, we populated the folding intermediate of the Thermus thermophilus ribonuclease H, which forms before the rate-limiting transition state, by removing the unfolded regions of the intermediate, including an alpha-helix and two beta-strands (51 folded residues). Using multidimensional NMR, we solved the structure of this intermediate mimic to an atomic resolution (backbone rmsd, 0.51 angstrom). It has a native-like backbone topology and shows some local deviations from the native structure, revealing that the structure of the folded region of an early folding intermediate can be as well defined as the native structure. The topological parameters calculated from the structures of the intermediate mimic and the native state predict that the intermediate should fold on a millisecond time scale or less and form much faster than the native state. Other factors that may lead to the slow folding of the native state and the accumulation of the intermediate before the rate-limiting transition state are also discussed. Published by Elsevier Ltd. C1 [Zhou, Zheng; Feng, Hanqiao; Bai, Yawen] NCI, Biochem & Mol Biol Lab, NIH, Bethesda, MD 20892 USA. [Ghirlando, Rodolfo] NIDDK, Mol Biol Lab, NIH, Bethesda, MD 20892 USA. RP Bai, YW (reprint author), NCI, Biochem & Mol Biol Lab, NIH, Bethesda, MD 20892 USA. EM yawen@helix.nih.gov RI Ghirlando, Rodolfo/A-8880-2009 FU National Cancer Institute; National Institute of Diabetes and Digestive and Kidney Diseases; National Institutes of Health FX We thank Walter Englander and Tobin Sosnick for their critical comments. This work is supported by the intramural research program of National Cancer Institute and National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health. NR 55 TC 14 Z9 14 U1 0 U2 5 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 12 PY 2008 VL 384 IS 2 BP 531 EP 539 DI 10.1016/j.jmb.2008.09.044 PG 9 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 377TC UT WOS:000261272500018 PM 18848567 ER PT J AU Khan, J Benoliel, R Herzberg, U Mannes, AJ Caudle, RM Young, A Eliav, E AF Khan, Junad Benoliel, Rafael Herzberg, Uri Mannes, Andrew J. Caudle, Robert M. Young, Andrew Eliav, Eli TI Bite force and pattern measurements for dental pain assessment in the rat SO NEUROSCIENCE LETTERS LA English DT Article DE Dental Pain; Bite force; Bite pattern ID MASSETER INHIBITORY PERIODS; TOOTH-PULP STIMULATION; MECHANICAL ALLODYNIA; IRREVERSIBLE PULPITIS; TRIGEMINAL PAIN; DISCRIMINATION; ENDURANCE; MODEL AB We present simple method to assess dental pain in the awake rat. Using a sensitive strain gauge we examined changes in bite strength and bite pattern in rats following dental injury. Rats with dental injury displayed a significant reduction in mean peak bite strength and an altered bite cluster pattern. Both changes in the dental injury rats were reversed by an analgesic dose of morphine, and this could be reversed with naloxone. These changes were not observed in naive control animals. This simple method significantly improves our ability to evaluate dental pain syndromes. (C) 2008 Elsevier Ireland Ltd. All rights reserved. C1 [Khan, Junad; Young, Andrew; Eliav, Eli] Univ Med & Dent New Jersey, Dept Diagnost Sci, Div Orofacial Pain,New Jersey Dent Sch, Suzan & Robert Carmel Endowed Chair Algesiol, Newark, NJ 07103 USA. [Benoliel, Rafael] Hadassah Hebrew Univ, Fac Med Dent, Dept Oral Med, Jerusalem, Israel. [Herzberg, Uri] Johnson & Johnson Med Device Grp, Ctr Biomat & Adv Technol, Somerville, NJ USA. [Mannes, Andrew J.] NIDCR, DASS, CC PNSB, NIH,DHH, Bethesda, MD USA. [Caudle, Robert M.] Univ Florida, Coll Dent, Dept Oral & Maxillofacial Surg, Gainesville, FL USA. RP Eliav, E (reprint author), Univ Med & Dent New Jersey, Dept Diagnost Sci, Div Orofacial Pain,New Jersey Dent Sch, Suzan & Robert Carmel Endowed Chair Algesiol, 110 Bergen St, Newark, NJ 07103 USA. EM eliavel@umdnj.edu RI Rastelli, Marcio/B-8034-2011; OI Mannes, Andrew/0000-0001-5834-5667 FU Intramural NIH HHS [Z99 CL999999] NR 23 TC 5 Z9 5 U1 0 U2 3 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0304-3940 J9 NEUROSCI LETT JI Neurosci. Lett. PD DEC 12 PY 2008 VL 447 IS 2-3 BP 175 EP 178 DI 10.1016/j.neulet.2008.70.008 PG 4 WC Neurosciences SC Neurosciences & Neurology GA 381PV UT WOS:000261549300017 PM 18926882 ER PT J AU Krueger, F Grafman, J McCabe, K AF Krueger, Frank Grafman, Jordan McCabe, Kevin TI Neural correlates of economic game playing SO PHILOSOPHICAL TRANSACTIONS OF THE ROYAL SOCIETY B-BIOLOGICAL SCIENCES LA English DT Review DE neuroeconomics; game theory; trust; reward; social; functional magnetic resonance imaging; oxytocin ID ANTERIOR CINGULATE CORTEX; TEMPORO-PARIETAL JUNCTION; RIGHT PREFRONTAL CORTEX; MIXED-STRATEGY GAME; THEORY-OF-MIND; DECISION-MAKING; PERSPECTIVE-TAKING; COMPETITIVE GAME; ULTIMATUM GAME; SHARED REPRESENTATIONS AB The theory of games provides a mathematical formalization of strategic choices, which have been studied in both economics and neuroscience, and more recently has become the focus of neuroeconomics experiments with human and non-human actors. This paper reviews the results from a number of game experiments that establish a unitary system for forming subjective expected utility maps in the brain, and acting on these maps to produce choices. Social situations require the brain to build an understanding of the other person using neuronal mechanisms that share affective and intentional mental states. These systems allow subjects to better predict other players' choices, and allow them to modify their subjective utility maps to value pro-social strategies. New results for a trust game are presented, which show that the trust relationship includes systems common to both trusting and trustworthy behaviour, but they also show that the relative temporal positions of first and second players require computations unique to that role. C1 [Krueger, Frank; McCabe, Kevin] George Mason Univ, Ctr Study Neuroecon, Fairfax, VA 22030 USA. [Krueger, Frank; Grafman, Jordan] NINDS, Cognit Neurosci Sect, NIH, Bethesda, MD 20892 USA. RP McCabe, K (reprint author), George Mason Univ, Ctr Study Neuroecon, 4400 Univ Dr,MSN 1G3, Fairfax, VA 22030 USA. EM kmccabe@gmu.edu FU NINDS; CNS/NINDS/NIH FX The authors are grateful to N. Armstrong, J. Moll, M. Strenziok and R. Zahn for their help in various stages of the fMRI experiment. The work was supported in part by a postdoctoral NINDS competitive fellowship award to F. K. and the Intramural Research Program of the CNS/NINDS/NIH. NR 122 TC 30 Z9 32 U1 20 U2 40 PU ROYAL SOC PI LONDON PA 6-9 CARLTON HOUSE TERRACE, LONDON SW1Y 5AG, ENGLAND SN 0962-8436 J9 PHILOS T R SOC B JI Philos. Trans. R. Soc. B-Biol. Sci. PD DEC 12 PY 2008 VL 363 IS 1511 BP 3859 EP 3874 DI 10.1098/rstb.2008.0165 PG 16 WC Biology SC Life Sciences & Biomedicine - Other Topics GA 371WY UT WOS:000260864600009 PM 18829425 ER PT J AU Boon, K Tomfohr, JK Bailey, NW Garantziotis, S Li, ZW Brass, DM Maruoka, S Hollingsworth, JW Schwartz, DA AF Boon, Kathy Tomfohr, John K. Bailey, Nathaniel W. Garantziotis, Stavros Li, Zhuowei Brass, David M. Maruoka, Shuichiro Hollingsworth, John W. Schwartz, David A. TI Evaluating genome-wide DNA methylation changes in mice by Methylation Specific Digital Karyotyping SO BMC GENOMICS LA English DT Article ID EPIGENETIC CHANGES; DISEASE; SUSCEPTIBILITY; EPIGENOMICS; COREST; GENES AB Background: The study of genome-wide DNA methylation changes has become more accessible with the development of various array-based technologies though when studying species other than human the choice of applications are limited and not always within reach. In this study, we adapted and tested the applicability of Methylation Specific Digital Karyotyping (MSDK), a non-array based method, for the prospective analysis of epigenetic changes after perinatal nutritional modifications in a mouse model of allergic airway disease. MSDK is a sequenced based method that allows a comprehensive and unbiased methylation profiling. The method generates 21 base pairs long sequence tags derived from specific locations in the genome. The resulting tag frequencies determine in a quantitative manner the methylation level of the corresponding loci. Results: Genomic DNA from whole lung was isolated and subjected to MSDK analysis using the methylation-sensitive enzyme Not I as the mapping enzyme and Nla III as the fragmenting enzyme. In a pair wise comparison of the generated mouse MSDK libraries we identified 158 loci that are significantly differentially methylated (P-value = 0.05) after perinatal dietary changes in our mouse model. Quantitative methylation specific PCR and sequence analysis of bisulfate modified genomic DNA confirmed changes in methylation at specific loci. Differences in genomic MSDK tag counts for a selected set of genes, correlated well with changes in transcription levels as measured by real-time PCR. Furthermore serial analysis of gene expression profiling demonstrated a dramatic difference in expressed transcripts in mice exposed to perinatal nutritional changes. Conclusion: The genome-wide methylation survey applied in this study allowed for an unbiased methylation profiling revealing subtle changes in DNA methylation in mice maternally exposed to dietary changes in methyl-donor content. The MSDK method is applicable for mouse models of complex human diseases in a mixed cell population and might be a valuable technology to determine whether environmental exposures can lead to epigenetic changes. C1 [Boon, Kathy; Tomfohr, John K.; Bailey, Nathaniel W.; Garantziotis, Stavros; Brass, David M.; Maruoka, Shuichiro; Schwartz, David A.] NHLBI, Natl Inst Environm Hlth Sci, Res Triangle Pk, NC 27709 USA. [Li, Zhuowei; Brass, David M.; Hollingsworth, John W.] Duke Univ, Med Ctr, Durham, NC 27710 USA. [Schwartz, David A.] Natl Jewish Hlth, Denver, CO 80206 USA. [Schwartz, David A.] Univ Colorado, Hlth Sci Ctr, Denver, CO 80206 USA. RP Boon, K (reprint author), NHLBI, Natl Inst Environm Hlth Sci, Res Triangle Pk, NC 27709 USA. EM boonc@mail.nih.gov; tomfohr@gmail.com; getnatbailey@gmail.com; garantziotis@niehs.nih.gov; zhuowei.li@duke.edu; david.brass@duke.edu; maruokas@niehs.nih.gov; holli017@mc.duke.edu; schwartzd@njc.org RI Garantziotis, Stavros/A-6903-2009 OI Garantziotis, Stavros/0000-0003-4007-375X FU NIEHS; NHLBI Intramural Research Programs [HL091335] FX This work was supported by NIEHS and NHLBI Intramural Research Programs (DAS) and HL091335 (JWH). NR 25 TC 3 Z9 3 U1 0 U2 2 PU BIOMED CENTRAL LTD PI LONDON PA CURRENT SCIENCE GROUP, MIDDLESEX HOUSE, 34-42 CLEVELAND ST, LONDON W1T 4LB, ENGLAND SN 1471-2164 J9 BMC GENOMICS JI BMC Genomics PD DEC 11 PY 2008 VL 9 AR 598 DI 10.1186/1471-2164-9-598 PG 10 WC Biotechnology & Applied Microbiology; Genetics & Heredity SC Biotechnology & Applied Microbiology; Genetics & Heredity GA 403VC UT WOS:000263109100003 PM 19077247 ER PT J AU Pierson, TC AF Pierson, Theodore C. TI Waste Not, Want Not: A Viral RNA Degradation Product Modulates West Nile Virus Pathogenesis SO CELL HOST & MICROBE LA English DT Editorial Material ID BODIES; CELLS AB In this issue of Cell Host & Microbe, Pijlman et al. define the structure and mechanism of generation of a small viral noncoding RNA present in flavivirus-infected cells that has a marked impact on the fate of infected cells and virulence in vivo. C1 NIH, Viral Pathogenesis Sect, Viral Dis Lab, Bethesda, MD 20892 USA. RP Pierson, TC (reprint author), NIH, Viral Pathogenesis Sect, Viral Dis Lab, Bethesda, MD 20892 USA. EM piersontc@mail.nih.gov NR 9 TC 2 Z9 2 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 11 PY 2008 VL 4 IS 6 BP 512 EP 513 DI 10.1016/j.chom.2008.11.004 PG 2 WC Microbiology; Parasitology; Virology SC Microbiology; Parasitology; Virology GA 388GB UT WOS:000262007200004 PM 19064251 ER PT J AU Neckers, L Tatu, U AF Neckers, Len Tatu, Utpal TI Molecular Chaperones in Pathogen Virulence: Emerging New Targets for Therapy SO CELL HOST & MICROBE LA English DT Review ID HEAT-SHOCK-PROTEIN; HUMAN EPITHELIAL-CELLS; NF-KAPPA-B; PLASMODIUM-FALCIPARUM; DRUG-RESISTANCE; LISTERIA-MONOCYTOGENES; HELICOBACTER-PYLORI; GENE-EXPRESSION; LEISHMANIA-DONOVANI; HSP90 INHIBITORS AB Infectious organisms have to cope with demanding and rapidly changing environments during establishment in the host. This is particularly relevant for pathogens that utilize different hosts to complete their life cycle. In addition to homeotic environmental challenges, other stressful factors, such as oxidative bursts, are often triggered in response to infection. It is not surprising that many successful pathogens have developed robust chaperone systems to conquer the stressful environments in the host. In addition to discussing ingenious ways by which pathogens have utilized chaperones, the potential of exploiting pathogen chaperones as drug targets is also discussed. C1 [Tatu, Utpal] Indian Inst Sci, Dept Biochem, Bangalore 560012, Karnataka, India. [Neckers, Len] NCI, Urol Oncol Branch, Ctr Canc Res, Bethesda, MD 20892 USA. RP Tatu, U (reprint author), Indian Inst Sci, Dept Biochem, Bangalore 560012, Karnataka, India. EM tatu@biochem.iisc.ernet.in FU Intramural NIH HHS [Z01 SC010074-12]; NCI NIH HHS [Z01 BC011032-01] NR 75 TC 41 Z9 42 U1 0 U2 3 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 11 PY 2008 VL 4 IS 6 BP 519 EP 527 DI 10.1016/j.chom.2008.10.011 PG 9 WC Microbiology; Parasitology; Virology SC Microbiology; Parasitology; Virology GA 388GB UT WOS:000262007200005 PM 19064253 ER PT J AU Peterson, MM Mack, JL Hall, PR Alsup, AA Alexander, SM Sully, EK Sawires, YS Cheung, AL Otto, M Gresham, HD AF Peterson, M. Michal Mack, Jessica L. Hall, Pamela R. Alsup, Anny A. Alexander, Susan M. Sully, Erin K. Sawires, Youhanna S. Cheung, Ambrose L. Otto, Michael Gresham, Hattie D. TI Apolipoprotein B Is an Innate Barrier against Invasive Staphylococcus aureus Infection SO CELL HOST & MICROBE LA English DT Article ID CHRONIC GRANULOMATOUS-DISEASE; LOW-DENSITY-LIPOPROTEIN; IN-VIVO; CRITICALLY-ILL; PLASMA-LIPOPROTEINS; ACUTE-INFLAMMATION; VIRULENCE; METABOLISM; ACTIVATION; DEATH AB Staphylococcus aureus is both a colonizer of humans and a cause of severe invasive infections. Although the genetic basis for phenotype switching from colonizing to invasive has received significant study, knowledge of host factors that antagonize the switch is limited. We show that VLDL and LDL lipoproteins interfere with this switch by antagonizing the S. aureus agr quorum-sensing system that upregulates genes required for invasive infection. The mechanism of antagonism entails binding of the major structural protein of these lipoproteins, apolipoprotein B, to an S. aureus autoinducing pheromone, preventing attachment of this pheromone to the bacteria and subsequent signaling through its receptor, AgrC. Mice deficient in plasma apolipoprotein 13, either genetically or pharmacologically, are more susceptible to invasive agr+ bacterial infection, but not to infection with an agr deletion mutant. Therefore, apolipoprotein B at homeostatic levels in blood is an essential innate defense effector against invasive S. aureus infection. C1 [Peterson, M. Michal; Mack, Jessica L.; Hall, Pamela R.; Alsup, Anny A.; Alexander, Susan M.; Sully, Erin K.; Sawires, Youhanna S.; Gresham, Hattie D.] Univ New Mexico, Sch Med, Dept Mol Genet & Microbiol, Albuquerque, NM 87131 USA. [Peterson, M. Michal; Mack, Jessica L.; Hall, Pamela R.; Alsup, Anny A.; Alexander, Susan M.; Sully, Erin K.; Sawires, Youhanna S.; Gresham, Hattie D.] Albuquerque Vet Affairs Med Ctr, Res Serv, Albuquerque, NM 87108 USA. [Hall, Pamela R.] Univ New Mexico, Sch Med, Dept Pathol, Albuquerque, NM 87131 USA. [Cheung, Ambrose L.] Dartmouth Med Sch, Dept Microbiol, Hanover, NH 03755 USA. [Otto, Michael] NIAID, Rocky Mt Lab, NIH, Hamilton, MT 59840 USA. RP Gresham, HD (reprint author), Univ New Mexico, Sch Med, Dept Mol Genet & Microbiol, Albuquerque, NM 87131 USA. EM hgresham@salud.unm.edu RI Hall, Pamela/O-5402-2016; OI Hall, Pamela/0000-0003-2367-3382; Otto, Michael/0000-0002-2222-4115 FU NIAID NIH HHS [R01 AI064926-01, AI 37142, AI 47441, AI-064926, R01 AI037142, R01 AI047441, R01 AI064926, R01 AI064926-02, R01 AI064926-03, R01 AI064926-04, T32 AI007538] NR 49 TC 68 Z9 71 U1 0 U2 10 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 11 PY 2008 VL 4 IS 6 BP 555 EP 566 DI 10.1016/j.chom.2008.10.001 PG 12 WC Microbiology; Parasitology; Virology SC Microbiology; Parasitology; Virology GA 388GB UT WOS:000262007200008 PM 19064256 ER PT J AU Giubellino, A Shi, ZD Jenkins, LMM Worthy, KM Bindu, LK Athauda, G Peruzzi, B Fisher, RJ Appella, E Burke, TR Bottaro, DP AF Giubellino, Alessio Shi, Zhen-Dan Jenkins, Lisa M. Miller Worthy, Karen M. Bindu, Lakshman K. Athauda, Gagani Peruzzi, Benedetta Fisher, Robert J. Appella, Ettore Burke, Terrence R., Jr. Bottaro, Donald P. TI Selectivity and Mechanism of Action of a Growth Factor Receptor-Bound Protein 2 Src Homology 2 Domain Binding Antagonist SO JOURNAL OF MEDICINAL CHEMISTRY LA English DT Article ID FOCAL-ADHESION KINASE; SH2 DOMAIN; GRB2; P21-ACTIVATED-KINASE-1; INHIBITION; LIGANDS; CANCER AB We have shown previously that a potent synthetic antagonist of growth factor receptor-bound protein 2 (Grb2) Src homology 2 (SH2) domain binding (1) blocks growth factor stimulated motility, invasion, and angiogenesis in cultured cell models, as well as tumor metastasis in animals. To characterize the selectivity of I for the SH2 domain of Grb2 over other proteins containing similar structural binding motifs, we synthesized a biotinylated derivative (3) that retained high affinity Grb2 SH2 domain binding and potent biological activity. To investigate the selectivity of 1 and 3 for Grb2, the biotinylated antagonist 3 was used to immobilize target proteins from cell extracts for subsequent identification by mass spectrometry. Nonspecific binding was identified in parallel using a biotinylated analogue that lacked a single critical binding determinant. The mechanism of action of the antagonist was further characterized by immunoprecipitation, immunoblotting, and light microscopy. This approach to defining protein binding antagonist selectivity and molecular basis of action should be widely applicable in drug development. C1 [Bottaro, Donald P.] NCI, Urol Oncol Branch, CCR, Bethesda, MD 20892 USA. [Jenkins, Lisa M. Miller; Appella, Ettore] NCI, Cell Biol Lab, Bethesda, MD 20892 USA. [Shi, Zhen-Dan; Burke, Terrence R., Jr.] NCI, Med Chem Lab, Frederick, MD 21702 USA. [Worthy, Karen M.; Bindu, Lakshman K.; Fisher, Robert J.] SAIC Frederick Inc, Prot Chem Lab, Frederick, MD 21702 USA. RP Bottaro, DP (reprint author), NCI, Urol Oncol Branch, CCR, Bldg 10 CRC 1,W Room 3961,10 Ctr Drivem MSC 1107, Bethesda, MD 20892 USA. EM dbottaro@helix.nih.gov RI Fisher, Robert/B-1431-2009; Bottaro, Donald/F-8550-2010; Burke, Terrence/N-2601-2014; OI Bottaro, Donald/0000-0002-5057-5334; Giubellino, Alessio/0000-0002-5352-0662 FU NIH, National Cancer Institute, Center for Cancer Research [N01-CO-12400] FX This research was supported by the Intramural Research Program of the NIH, National Cancer Institute, Center for Cancer Research. This project has been funded in part with federal funds from the National Cancer Institute, National Institutes of Health, under Contract N01-CO-12400. The content of this publication does not necessarily reflect the views or policies of the Department of Health and Human Services, nor does mention of trade names, commercial products, or organizations imply endorsement by the U.S. Government. NR 28 TC 7 Z9 8 U1 0 U2 2 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 11 PY 2008 VL 51 IS 23 BP 7459 EP 7468 DI 10.1021/jm800523u PG 10 WC Chemistry, Medicinal SC Pharmacology & Pharmacy GA 379XG UT WOS:000261429100014 PM 18989951 ER PT J AU Gupte, A Boshoff, HI Wilson, DJ Neres, J Labello, NP Somu, RV Xing, CG Barry, CE Aldrich, CC AF Gupte, Amol Boshoff, Helena I. Wilson, Daniel J. Neres, Joao Labello, Nicholas P. Somu, Ravindranadh V. Xing, Chengguo Barry, Clifton E., III Aldrich, Courtney C. TI Inhibition of Siderophore Biosynthesis by 2-Triazole Substituted Analogues of 5'-O-[N-(Salicyl)sulfamoyl]adenosine: Antibacterial Nucleosides Effective against Mycobacterium tuberculosis SO JOURNAL OF MEDICINAL CHEMISTRY LA English DT Article ID ANTITUBERCULAR AGENTS; PEPTIDE SYNTHETASES; COUPLING REACTIONS; RECEPTOR AGONISTS; IRON ACQUISITION; TERMINAL ALKYNES; FACILE SYNTHESIS; AZIDES; ENZYME; DOMAIN AB The synthesis, biochemical, and biological evaluation of a systematic series of 2-triazole derivatives of 5'-O-[N-(salicyl)sulfamoyl]adenosine (Sal-AMS) are described as inhibitors of aryl acid adenylating enzymes (AAAE) involved in siderophore biosynthesis by Mycobacterium tuberculosis. Structure-activity relationships revealed a remarkable ability to tolerate a wide range of substituents at the 4-position of the triazole moiety, and a majority of the Compounds possessed subnanomolar apparent inhibition constants. However, the in vitro potency did not always translate into whole cell biological activity against M. tuberculosis, suggesting that intrinsic resistance plays an important role in the observed activities. Additionally, the well-known valence tautomerism between 2-azidopurines and their fused tetrazole counterparts led to an unexpected facile acylation of the purine N-6 amino group. C1 [Gupte, Amol; Wilson, Daniel J.; Neres, Joao; Labello, Nicholas P.; Somu, Ravindranadh V.; Aldrich, Courtney C.] Univ Minnesota, Acad Hlth Ctr, Ctr Drug Design, Minneapolis, MN 55455 USA. [Boshoff, Helena I.; Barry, Clifton E., III] NIAID, TB Res Sect, Bethesda, MD 20892 USA. [Xing, Chengguo] Univ Minnesota, Dept Med Chem, Minneapolis, MN 55455 USA. RP Aldrich, CC (reprint author), Univ Minnesota, Acad Hlth Ctr, Ctr Drug Design, Minneapolis, MN 55455 USA. EM aldri015@umn.edu RI Barry, III, Clifton/H-3839-2012; Neres, Joao/A-1241-2011 OI Neres, Joao/0000-0003-4488-2423 FU NIH [R01A1070219]; Center for Drug Design; Academic Health Center; University of Minnesota; NIH, National Institute of Allergy and Infectious Disease FX This research was supported by a grant from the NIH (Grant R01A1070219) and funding from the Center for Drug Design, Academic Health Center, University of Minnesota to C.C.A. This research was supported in part by the Intramural Research Program of the NIH, National Institute of Allergy and Infectious Disease. We thank the Minnesota Supercomputing Institute for computing time. NR 42 TC 59 Z9 60 U1 1 U2 13 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 11 PY 2008 VL 51 IS 23 BP 7495 EP 7507 DI 10.1021/jm8008037 PG 13 WC Chemistry, Medicinal SC Pharmacology & Pharmacy GA 379XG UT WOS:000261429100018 PM 19053762 ER PT J AU Andreani, A Burnelli, S Granaiola, M Leoni, A Locatelli, A Morigi, R Rambaldi, M Varoli, L Calonghi, N Cappadone, C Voltattomi, M Zini, M Stefanelli, C Masotti, L Shoemaker, RH AF Andreani, Aldo Burnelli, Silvia Granaiola, Massimiliano Leoni, Alberto Locatelli, Alessandra Morigi, Rita Rambaldi, Mirella Varoli, Lucilla Calonghi, Natalia Cappadone, Concettina Voltattomi, Manuela Zini, Maddalena Stefanelli, Claudio Masotti, Lanfranco Shoemaker, Robert H. TI Antitumor Activity of New Substituted 3-(5-Imidazo[2,1-b]thiazolylmethylene)-2-indolinones and 3-(5-Imidazo[2,1-b]thiadiazolylmethylene)-2-indolinones: Selectivity against Colon Tumor Cells and Effect on Cell Cycle-Related Events SO JOURNAL OF MEDICINAL CHEMISTRY LA English DT Article ID DERIVATIVES; CANCER; POLYAMINES AB The synthesis of new 3-(5-imidazo[2,1-b]thiazolylmethylene)-2-indolinones and 3-(5-imidazo[2,1-b]thiadiazolylmethylene)-2-indolinones is reported. The antitumor activity was evaluated according to the protocols available at the National Cancer Institute (NCI), Bethesda, MD. To investigate the mechanism of action of the most potent antitumor agent of this series, its effect on growth of HT-29 colon carcinoma cells was studied. Its ability to inhibit cellular proliferation was mediated by cell cycle arrest at the G2/M phase, accompanied by inhibition of ornithine decarboxylase (ODC), the limiting enzyme of polyamine synthesis, and followed by induction of apoptosis. C1 [Andreani, Aldo; Burnelli, Silvia; Granaiola, Massimiliano; Leoni, Alberto; Locatelli, Alessandra; Morigi, Rita; Rambaldi, Mirella; Varoli, Lucilla] Univ Bologna, Dipartimento Sci Farmaceut, I-40126 Bologna, Italy. [Calonghi, Natalia; Cappadone, Concettina; Zini, Maddalena; Stefanelli, Claudio; Masotti, Lanfranco] Univ Bologna, Dipartimento Biochim G Moruzzi, I-40126 Bologna, Italy. [Voltattomi, Manuela] Univ Bologna, CIRB, I-40127 Bologna, Italy. [Shoemaker, Robert H.] NCI, Screening Technol Branch, Dev Therapeut Program, Div Canc Treatment & Diag, Frederick, MD 21702 USA. RP Andreani, A (reprint author), Univ Bologna, Dipartimento Sci Farmaceut, Via Belmeloro 6, I-40126 Bologna, Italy. EM aldo.andreani@unibo.it OI STEFANELLI, CLAUDIO/0000-0001-5864-2178; LEONI, ALBERTO/0000-0001-8528-8207 FU MIUR-COFIN FX This work was supported by a grant from MIUR-COFIN 2006. We are grateful to NCI for the antitumor tests and to CIRB for the use of confocal microscope and flow cytometer. NR 23 TC 31 Z9 32 U1 0 U2 1 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 11 PY 2008 VL 51 IS 23 BP 7508 EP 7513 DI 10.1021/jm800827q PG 6 WC Chemistry, Medicinal SC Pharmacology & Pharmacy GA 379XG UT WOS:000261429100019 PM 19006285 ER PT J AU Yoo, CB Valente, R Congiatu, C Gavazza, F Angel, A Siddiqui, MA Jones, PA McGuigan, C Marquez, VE AF Yoo, Christine B. Valente, Rocco Congiatu, Costantino Gavazza, Federica Angel, Annette Siddiqui, Maqbool A. Jones, Peter A. McGuigan, Christopher Marquez, Victor E. TI Activation of p16 Gene Silenced by DNA Methylation in Cancer Cells by Phosphoramidate Derivatives of 2 '-Deoxyzebularine SO JOURNAL OF MEDICINAL CHEMISTRY LA English DT Article ID EPIGENETICALLY BASED STRATEGY; 2,3-DIDEHYDRO-2,3-DIDEOXYADENOSINE D4A; CYTIDINE DEAMINASE; UNIQUE MOLECULE; ZEBULARINE; INHIBITION; CHEMOTHERAPY; CONVERSION; MECHANISM; THERAPY AB We report herein the application of the phosphoramidate ProTide technology to improve the metabolism of the DNA methytransferase inhibitor, zebularine (Z). Zebularine is a riboside that must undergo a complex metabolic transformation before reaching the critical 2'-deoxyzebularine 5'-triphosphate (dZTP). Because 2'-deoxyzebularine (dZ) is not phosphorylated and therefore inactive, the ProTide strategy was employed to bypass the lack of phosphorylation of dZ and the inefficient reduction of zebularine 5'-diphosphate by ribonucleotide-diphosphate reductase required for zebularine. Several compounds were identified as more potent inhibitors of DNA methylation and stronger inducers of p16 tumor suppressor gene than zebularine. However, their activity was dependent on the administration of thymidine to overcome the potent inhibition of thymidylate synthase (TS) and deoxycytidine monophosphate (dCMP) deaminase by dZMP, which deprives cells of essential levels of thymidine. Intriguingly, the activity of the ProTides was cell line-dependent, and activation of p16 was manifest only in Cf-Pac-1 pancreatic ductal adenocarcinoma. cells. C1 [Yoo, Christine B.; Jones, Peter A.] Univ So Calif, Dept Biochem, Keck Sch Med, USC Norris Comprehens Canc Ctr, Los Angeles, CA 90033 USA. [Yoo, Christine B.; Jones, Peter A.] Univ So Calif, Dept Mol Biol, Keck Sch Med, USC Norris Comprehens Canc Ctr, Los Angeles, CA 90033 USA. [Valente, Rocco; Congiatu, Costantino; Gavazza, Federica; Angel, Annette; McGuigan, Christopher] Cardiff Univ, Welsh Sch Pharm, Cardiff CF10 3XF, S Glam, Wales. [Siddiqui, Maqbool A.; Marquez, Victor E.] NIH, Natl Canc Inst, Ctr Canc Res, Med Chem Lab, Frederick, MD 21702 USA. RP Jones, PA (reprint author), Univ So Calif, Dept Biochem, Keck Sch Med, USC Norris Comprehens Canc Ctr, Los Angeles, CA 90033 USA. EM jones_p@cent.hsc.usc.edu; mcguigan@cf.ac.uk; marquezv@mail.nih.gov RI McGuigan, Chris/P-1580-2014 OI McGuigan, Chris/0000-0001-8409-710X FU NIH, Center for Cancer Research, NCI-Frederick FX This research was supported in part by the Intramural Research Program of the NIH, Center for Cancer Research, NCI-Frederick. NR 28 TC 13 Z9 14 U1 0 U2 4 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 11 PY 2008 VL 51 IS 23 BP 7593 EP 7601 DI 10.1021/jm8005965 PG 9 WC Chemistry, Medicinal SC Pharmacology & Pharmacy GA 379XG UT WOS:000261429100028 PM 19006382 ER PT J AU Bredemeyer, AL Helmink, BA Innes, CL Calderon, B McGinnis, LM Mahowald, GK Gapud, EJ Walker, LM Collins, JB Weaver, BK Mandik-Nayak, L Schreiber, RD Allen, PM May, MJ Paules, RS Bassing, CH Sleckman, BP AF Bredemeyer, Andrea L. Helmink, Beth A. Innes, Cynthia L. Calderon, Boris McGinnis, Lisa M. Mahowald, Grace K. Gapud, Eric J. Walker, Laura M. Collins, Jennifer B. Weaver, Brian K. Mandik-Nayak, Laura Schreiber, Robert D. Allen, Paul M. May, Michael J. Paules, Richard S. Bassing, Craig H. Sleckman, Barry P. TI DNA double-strand breaks activate a multi-functional genetic program in developing lymphocytes SO NATURE LA English DT Article ID NF-KAPPA-B; LEAKY SCID PHENOTYPE; V(D)J RECOMBINATION; LYMPHOID ORGANS; IONIZING-RADIATION; BONE-MARROW; ATM; EXPRESSION; DAMAGE; DIFFERENTIATION AB DNA double- strand breaks are generated by genotoxic agents and by cellular endonucleases as intermediates of several important physiological processes. The cellular response to genotoxic DNA breaks includes the activation of transcriptional programs known primarily to regulate cell- cycle checkpoints and cell survival(1-5). DNA double- strand breaks are generated in all developing lymphocytes during the assembly of antigen receptor genes, a process that is essential for normal lymphocyte development. Here we show that in murine lymphocytes these physiological DNA breaks activate a broad transcriptional program. This program transcends the canonical DNA double- strand break response and includes many genes that regulate diverse cellular processes important for lymphocyte development. Moreover, the expression of several of these genes is regulated similarly in response to genotoxic DNA damage. Thus, physiological DNA double- strand breaks provide cues that can regulate cell- type- specific processes not directly involved in maintaining the integrity of the genome, and genotoxic DNA breaks could disrupt normal cellular functions by corrupting these processes. C1 [Bredemeyer, Andrea L.; Helmink, Beth A.; Calderon, Boris; McGinnis, Lisa M.; Mahowald, Grace K.; Gapud, Eric J.; Walker, Laura M.; Weaver, Brian K.; Mandik-Nayak, Laura; Schreiber, Robert D.; Allen, Paul M.; Sleckman, Barry P.] Washington Univ, Sch Med, Dept Pathol & Immunol, St Louis, MO 63110 USA. [Innes, Cynthia L.; Collins, Jennifer B.; Paules, Richard S.] NIEHS, Environm Stress & Canc Grp, Res Triangle Pk, NC 27709 USA. [Innes, Cynthia L.; Collins, Jennifer B.; Paules, Richard S.] NIEHS, Microarray Grp, Res Triangle Pk, NC 27709 USA. [May, Michael J.] Univ Penn, Sch Vet Med, Philadelphia, PA 19104 USA. [Bassing, Craig H.] Univ Penn, Sch Med, Childrens Hosp Philadelphia, Ctr Childhood Canc Res,Dept Pathol & Lab Med, Philadelphia, PA 19104 USA. [Bassing, Craig H.] Abramson Family Canc Res Inst, Philadelphia, PA 19104 USA. RP Sleckman, BP (reprint author), Washington Univ, Sch Med, Dept Pathol & Immunol, St Louis, MO 63110 USA. EM Sleckman@immunology.wustl.edu RI Schreiber, Robert/A-1276-2013; OI Schreiber, Robert/0000-0001-6311-0432; Bredemeyer, Andrea/0000-0003-2970-5998; May, Michael/0000-0002-2485-3716; Calderon, Boris/0000-0003-1575-0739 FU National Institutes of Health [AI47829]; Washington University Department of Pathology and Immunology; Department of Pathology and Center for Childhood Cancer Research of the Children's Hospital of Philadelphia; Abramson Family Cancer Research Institute; National Institute of Environmental Health Sciences; Research Scholar Award from the American Cancer Society FX We thank J. Bednarski, B. Van Honten andM. Diaz for critical review of the manuscript, F. W. Alt for providing us with the Artemis 2/2 mice and D. Ballard for providing us with the I kappa B alpha-Delta N construct. This research is supported by the National Institutes of Health (NIH, grant AI47829) and the Washington University Department of Pathology and Immunology ( to B.P.S.); the Department of Pathology and Center for Childhood Cancer Research of the Children's Hospital of Philadelphia, and the Abramson Family Cancer Research Institute (to C.H.B.); and the intramural research program of the NIH, National Institute of Environmental Health Sciences (to R.S.P.). B.P.S. is a recipient of a Research Scholar Award from the American Cancer Society. C.H.B. is a Pew Scholar in the Biomedical Sciences. A.L.B. is supported by a post-doctoral training grant from the NIH. NR 38 TC 65 Z9 69 U1 1 U2 4 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 11 PY 2008 VL 456 IS 7223 BP 819 EP U113 DI 10.1038/nature07392 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 381TX UT WOS:000261559900055 PM 18849970 ER PT J AU Mattson, MP Gleichmann, M Cheng, A AF Mattson, Mark P. Gleichmann, Marc Cheng, Aiwu TI Mitochondria in Neuroplasticity and Neurological Disorders SO NEURON LA English DT Review ID AMYOTROPHIC-LATERAL-SCLEROSIS; CYTOCHROME-C RELEASE; APOPTOSIS-INDUCING FACTOR; FOCAL CEREBRAL-ISCHEMIA; PERMEABILITY TRANSITION PORE; EXCITOTOXIC NEURONAL DEATH; MAJOR DEPRESSIVE DISORDER; AMYLOID PRECURSOR PROTEIN; SYNUCLEIN TRANSGENIC MICE; CEREBELLAR GRANULE CELLS AB Mitochondrial electron transport generates the ATP that is essential for the excitability and survival of neurons, and the protein phosphorylation reactions that mediate synaptic signaling and related long-term changes in neuronal structure and function. Mitochondria are highly dynamic organelles that divide, fuse, and move purposefully within axons and dendrites. Major functions of mitochondria in neurons include the regulation of Ca(2+) and redox signaling, developmental and synaptic plasticity, and the arbitration of cell survival and death. The importance of mitochondria in neurons is evident in the neurological phenotypes in rare diseases caused by mutations in mitochondrial genes. Mitochondria-mediated oxidative stress, perturbed Ca(2+) homeostasis, and apoptosis may also contribute to the pathogenesis of prominent neurological diseases including Alzheimer's, Parkinson's, and Huntington's diseases; stroke; annyotrophic lateral sclerosis; and psychiatric disorders. Advances in understanding the molecular and cell biology of mitochondria are leading to novel approaches for the prevention and treatment of neurological disorders. C1 [Mattson, Mark P.; Gleichmann, Marc; Cheng, Aiwu] Natl Inst Aging Intramural Res Program, Neurosci Lab, Baltimore, MD 21224 USA. RP Mattson, MP (reprint author), Natl Inst Aging Intramural Res Program, Neurosci Lab, Baltimore, MD 21224 USA. EM mattsonm@grc.nia.nih.gov RI Mattson, Mark/F-6038-2012 FU National Institute on Aging Intramural Research Program of the NIH FX The authors thank KC Alexander for preparing the illustrations for the Figures of this manuscript. This work was supported by the National Institute on Aging Intramural Research Program of the NIH. NR 206 TC 344 Z9 352 U1 3 U2 53 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 0896-6273 J9 NEURON JI Neuron PD DEC 11 PY 2008 VL 60 IS 5 BP 748 EP 766 DI 10.1016/j.neuron.2008.10.010 PG 19 WC Neurosciences SC Neurosciences & Neurology GA 384LQ UT WOS:000261746700008 PM 19081372 ER PT J AU Schoen, RE Pinsky, PF AF Schoen, Robert E. Pinsky, Paul F. TI Five-Year Risk of Colorectal Neoplasia after Negative Colonoscopy SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Letter ID SCREENING COLONOSCOPY; SURVEILLANCE C1 [Schoen, Robert E.] Univ Pittsburgh, Sch Med, Pittsburgh, PA 15213 USA. [Pinsky, Paul F.] NCI, Bethesda, MD 20892 USA. RP Schoen, RE (reprint author), Univ Pittsburgh, Sch Med, Pittsburgh, PA 15213 USA. EM rschoen@pitt.edu NR 5 TC 0 Z9 0 U1 0 U2 0 PU MASSACHUSETTS MEDICAL SOC PI WALTHAM PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD DEC 11 PY 2008 VL 359 IS 24 BP 2611 EP 2611 PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA 381KG UT WOS:000261534200018 PM 19073983 ER PT J AU Jeang, KT AF Jeang, Kuan-Teh TI The 2008 Retrovirology Prize: Ben Berkhout and his RNA world SO RETROVIROLOGY LA English DT Editorial Material ID HIV-1; SCIENCE; GENOME; LIFE; WINS AB Ben Berkhout wins the 2008 Retrovirology Prize. 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 NR 11 TC 4 Z9 4 U1 0 U2 0 PU BIOMED CENTRAL LTD PI LONDON PA CURRENT SCIENCE GROUP, MIDDLESEX HOUSE, 34-42 CLEVELAND ST, LONDON W1T 4LB, ENGLAND SN 1742-4690 J9 RETROVIROLOGY JI Retrovirology PD DEC 11 PY 2008 VL 5 AR 113 DI 10.1186/1742-4690-5-113 PG 5 WC Virology SC Virology GA 394JI UT WOS:000262442600001 PM 19077224 ER PT J AU Bianco, C Mysliwiec, M Watanabe, K Mancino, M Nagaoka, T Gonzales, M Salomon, DS AF Bianco, Caterina Mysliwiec, Margaret Watanabe, Kazuhide Mancino, Mario Nagaoka, Tadahiro Gonzales, Monica Salomon, David S. TI Activation of a Nodal-independent signaling pathway by Cripto-1 mutants with impaired activation of a Nodal-dependent signaling pathway SO FEBS LETTERS LA English DT Article DE Cripto-1; Nodal; Glypican-1; Fucosylation; Mammary epithelial cell ID MAMMARY EPITHELIAL-CELLS; FUCOSYLATION AB Cripto-1, a co-receptor for Nodal, can activate Nodal-dependent and Nodal-independent signaling pathways. In this study we have investigated whether Cripto-1 mutants, that fail to activate a Nodal-dependent signaling pathway, are capable to activate a Nodal-independent signaling pathway in mammary epithelial cells. Cripto-1 mutants expressed in EpH4 mouse mammary epithelial cells are fully functional in regard to activation of a Nodal-independent signaling pathway, leading to phosphorylation of mitogen-activated protein kinase (MAPK) and Akt and to enhanced proliferation and motility of these cells, suggesting that Cripto-1 mutants with impaired Nodal signaling are still active in a Nodal-independent signaling pathway. C1 [Bianco, Caterina; Mysliwiec, Margaret; Watanabe, Kazuhide; Mancino, Mario; Nagaoka, Tadahiro; Gonzales, Monica; Salomon, David S.] NCI, Mammary Biol & Tumorigenesis Lab, NIH, Bethesda, MD 20892 USA. RP Salomon, DS (reprint author), NCI, Mammary Biol & Tumorigenesis Lab, NIH, 37 Convent Dr,Bldg 37,Room 1112, Bethesda, MD 20892 USA. EM biancoc@mail.nih.gov; salomond@mail.nih.gov OI Nagaoka, Tadahiro/0000-0002-9391-0243 FU NIH; NCI; CCR FX We would like to thank Pamela Stanley (Albert Einstein College of Medicine, New York) for generously providing the Cripto-1 mutant plasmids. We would like to thank Christina Baraty for her excellent technical assistance. This work was supported by Intramural Research program of the NIH, NCI, CCR. NR 16 TC 7 Z9 8 U1 0 U2 0 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 10 PY 2008 VL 582 IS 29 BP 3997 EP 4002 DI 10.1016/j.febslet.2008.10.052 PG 6 WC Biochemistry & Molecular Biology; Biophysics; Cell Biology SC Biochemistry & Molecular Biology; Biophysics; Cell Biology GA 377ES UT WOS:000261235100006 PM 19013461 ER PT J AU Chriqui, JF Tynan, M Agurs-Collins, T Masse, LC AF Chriqui, Jamie F. Tynan, Michael Agurs-Collins, Tanya Masse, Louise C. TI Will web-based research suffice when collecting US school district policies? The case of physical education and school-based nutrition policies SO INTERNATIONAL JOURNAL OF BEHAVIORAL NUTRITION AND PHYSICAL ACTIVITY LA English DT Article ID STATE POLICY; SOFT DRINKS; OVERWEIGHT; PREVALENCE; OBESITY; HEALTH; ADOLESCENTS; CHILDREN; IMPACT; RATES AB Background: Recognizing the growing childhood overweight problem, a number of school-based strategies, including policy approaches, have been proposed and are being implemented to address the problem considering the amount of time children spend in schools. This paper describes the results of a pilot study that tested approaches to collecting U. S. school district policy information regarding physical education and nutrition requirements that can inform efforts by policy makers, researchers, advocates and others interested in collecting school district-level obesity-related policies that are typically not systematically available from a "one stop" source. Methods: Sixty local school districts representing six states were selected for conducting the district policy research, with larger, urban school districts over-sampled to facilitate collection of policies from districts representing a larger proportion of the public school population in each study state. The six states within which the pilot districts were located were chosen based on the variability in their physical education and school-based nutrition policy and geographic and demographic diversity. Web research and a mail canvass of the study districts was conducted between January and May 2006 to obtain all relevant policies. An additional field collection effort was conducted in a sample of districts located in three study states to test the extent to which field collection would yield additional information. Results: Policies were obtained from 40 (67%) of the 60 districts, with policies retrieved via both Web and mail canvass methods in 16 (27%) of the districts, and were confirmed to not exist in 10 (17%) of the districts. Policies were more likely to be retrieved from larger, urban districts, whereas the smallest districts had no policies available on the Web. In no instances were exactly the same policies retrieved from the two sources. Physical education policies were slightly more prevalent than nutrition policies. Conclusion: Collection of U.S. local school district policies requires a multi-pronged approach. Web research and mail canvasses will likely yield different types of policy information. Given the variance in district-level Web site presence, researchers and others interested in obtaining district physical education and nutrition-related policies should consider supplementing Web research with more direct methods. C1 [Chriqui, Jamie F.] Univ Illinois, Inst Hlth Res & Policy, Chicago, IL 60608 USA. [Chriqui, Jamie F.] MayaTech Corp, Silver Spring, MD 20910 USA. [Agurs-Collins, Tanya] NCI, Bethesda, MD 20852 USA. [Masse, Louise C.] Univ British Columbia, Dept Pediat, CCHR Ctr Community Child Hlth Res, Vancouver, BC V6H 3V4, Canada. RP Chriqui, JF (reprint author), Univ Illinois, Inst Hlth Res & Policy, 1747 W Roosevelt Rd,MC 275, Chicago, IL 60608 USA. EM jchriqui@uic.edu; mtynan01@yahoo.com; collinsta@mail.nih.gov; lmasse@cw.bc.ca FU NCI [N02-PC-444006, 263-MQ-515012] FX Support for this project was provided by the NCI to The MayaTech Corporation through contract numbers N02-PC-444006 and 263-MQ-515012. The authors would like to gratefully acknowledge the research assistance provided by Carissa Holmes, Shelby Eidson, J.D., and Jim Igoe, M.A., M.L.S.. Michael Tynan and Jim Igoe were employed by MayaTech at the time of their contribution. Additionally, the authors would like to acknowledge the input provided by Drs. Amy Yaroch and Audie Autienza at NCI as part of a larger study framework of which this study was a part and Anna Sandavol, M. P. H. at the University of Illinois at Chicago, Institute for Health Research and Policy who assisted with field-based collection in one of our study states. The views presented in this paper are those of the authors and do not, necessarily, reflect those of the U.S. Department of Health and Human Services or any of the authors' employers. NR 28 TC 2 Z9 2 U1 2 U2 4 PU BIOMED CENTRAL LTD PI LONDON PA CURRENT SCIENCE GROUP, MIDDLESEX HOUSE, 34-42 CLEVELAND ST, LONDON W1T 4LB, ENGLAND SN 1479-5868 J9 INT J BEHAV NUTR PHY JI Int. J. Behav. Nutr. Phys. Act. PD DEC 10 PY 2008 VL 5 AR 64 DI 10.1186/1479-5868-5-64 PG 9 WC Nutrition & Dietetics; Physiology SC Nutrition & Dietetics; Physiology GA 405PY UT WOS:000263237900001 PM 19077186 ER PT J AU Kato, GJ Gladwin, MT AF Kato, Gregory J. Gladwin, Mark T. TI Evolution of Novel Small-Molecule Therapeutics Targeting Sickle Cell Vasculopathy SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Article ID MICROVASCULAR ENDOTHELIAL-CELLS; OXIDE SYNTHASE INHIBITOR; NITRIC-OXIDE; PULMONARY-HYPERTENSION; ADHESION MOLECULES; PLATELET ACTIVATION; HEME OXYGENASE-1; ASYMMETRIC DIMETHYLARGININE; ISCHEMIA-REPERFUSION; VASOOCCLUSIVE CRISIS AB A 34- year- old African American woman with sickle cell disease and history of relatively severe hemolysis, chronic leg ulcers, and mild pulmonary hypertension presented with a new ischemic stroke. Recent research has suggested a syndrome of hemolysis- associated vasculopathy in patients with sickle cell disease, which features severe hemolytic anemia and leads to scavenging of nitric oxide and its biochemical precursor L- arginine. This diminished bioavailability of nitric oxide promotes a hemolysis-vascular dysfunction syndrome, which includes pulmonary hypertension, cutaneous leg ulceration, priapism, and ischemic stroke. Additional correlates of this vasculopathy include activation of endothelial cell adhesion molecules, platelets, and the vascular protectant hemeoxygenase- 1. Some known risk factors for atherosclerosis are also associated with sickle cell vasculopathy, including low levels of apolipoprotein AI and high levels of asymmetric dimethylarginine, an endogenous inhibitor of nitric oxide synthase. Identification of dysregulated vascular biology pathways in sickle vasculopathy has provided a focus for new clinical trials for therapeutic intervention, including inhaled nitric oxide, sodium nitrite, L- arginine, phosphodiesterase- 5 inhibitors, niacin, inhaled carbon monoxide, and endothelin receptor antagonists. This article reviews the pathophysiology of sickle vasculopathy and the results of preliminary clinical trials of novel small- molecule therapeutics directed at abnormal vascular biology in patients with sickle cell disease. C1 [Kato, Gregory J.] NHLBI, Dept Crit Care Med, Ctr Clin, NIH, Bethesda, MD 20892 USA. [Kato, Gregory J.] NHLBI, Pulm & Vasc Med Branch, NIH, Bethesda, MD 20892 USA. [Gladwin, Mark T.] Univ Pittsburgh, Med Ctr, Div Pulm Allergy & Crit Care Med, Dept Med, Pittsburgh, PA USA. [Gladwin, Mark T.] Hemostasis & Vasc Biol Res Inst, Pittsburgh, PA USA. RP Kato, GJ (reprint author), NHLBI, Dept Crit Care Med, Ctr Clin, NIH, 10 Ctr Dr,MSC 1476,Bldg 10 CRC,Room 5-5140, Bethesda, MD 20892 USA. EM gkato@mail.nih.gov RI Kato, Gregory/I-7615-2014 OI Kato, Gregory/0000-0003-4465-3217 FU Department of Intramural Research of the NIH Clinical Center; National Heart, Lung, and Blood Institute; Institute of Transfusion Medicine; Hemophilia Center of Western Pennsylvania; NIH Collaborative Research and Development Agreement FX Drs Kato and Gladwin have been supported by intramural funds from the Department of Intramural Research of the NIH Clinical Center and the National Heart, Lung, and Blood Institute (NHLBI). Dr Gladwin currently receives support from the Institute of Transfusion Medicine, the Hemophilia Center of Western Pennsylvania, and grant support through an NIH Collaborative Research and Development Agreement of inhaled nitric oxide gas with Ikaria. NR 82 TC 43 Z9 45 U1 0 U2 4 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 10 PY 2008 VL 300 IS 22 BP 2638 EP 2646 DI 10.1001/jama.2008.598 PG 9 WC Medicine, General & Internal SC General & Internal Medicine GA 380YW UT WOS:000261503000023 PM 19066384 ER PT J AU Hahn, T McCarthy, PL Zhang, MJ Wang, D Arora, M Frangoul, H Gale, RP Hale, GA Horan, J Isola, L Maziarz, RT van Rood, JJ Gupta, V Halter, J Reddy, V Tiberghien, P Litzow, M Anasetti, C Pavletic, S Ringden, O AF Hahn, Theresa McCarthy, Philip L., Jr. Zhang, Mei-Jie Wang, Dan Arora, Mukta Frangoul, Haydar Gale, Robert Peter Hale, Gregory A. Horan, John Isola, Luis Maziarz, Richard T. van Rood, Jon J. Gupta, Vikas Halter, Joerg Reddy, Vijay Tiberghien, Pierre Litzow, Mark Anasetti, Claudio Pavletic, Stephen Ringden, Olle TI Risk Factors for Acute Graft-Versus-Host Disease After Human Leukocyte Antigen-Identical Sibling Transplants for Adults With Leukemia SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article ID BONE-MARROW-TRANSPLANTATION; TOTAL-BODY IRRADIATION; STEM-CELL TRANSPLANTATION; CHRONIC MYELOID-LEUKEMIA; RANDOMIZED-TRIAL; CYCLOSPORINE CONCENTRATION; PREPARATIVE REGIMEN; BUSULFAN-CYTOXAN; FRENCH-SOCIETY; SURVIVAL AB Purpose Acute graft-versus-host disease (GVHD) causes substantial morbidity and mortality after human leukocyte antigen (HLA)-identical sibling transplants. No large registry studies of acute GVHD risk factors have been reported in two decades. Risk factors may have changed in this interval as transplant-related techniques have evolved. Patients and Methods Acute GVHD risk factors were analyzed in 1,960 adults after HLA-identical sibling myeloablative transplant for acute myeloid leukemia (AML), acute lymphocytic leukemia (ALL), or chronic myeloid leukemia (CML) reported by 226 centers worldwide to the Center for International Blood and Marrow Transplant Research from 1995 to 2002. Outcome was measured as time from transplant to onset of grade 2 to 4 acute GVHD, with death without acute GVHD as a competing risk. Results Cumulative incidence of grade 2 to 4 acute GVHD was 35% (95% CI, 33% to 37%). In multivariable analyses, factors significantly associated with grade 2 to 4 acute GVHD were cyclophosphamide + total-body irradiation versus busulfan + cyclophosphamide (relative risk [RR] = 1.4; P < .0001), blood cell versus bone marrow grafts in patients age 18 to 39 years (RR = 1.43; P = .0023), recipient age 40 and older versus age 18 to 39 years receiving bone marrow grafts (RR = 1.44; P = .0005), CML versus AML/ALL (RR = 1.35; P = .0003), white/Black versus Asian/Hispanic race (RR = 1.54; P = .0003), Karnofsky performance score less than 90 versus 90 to 100 (RR = 1.27; P = .014), and recipient/donor cytomegalovirus-seronegative versus either positive (RR = 1.20; P = .04). Stratification by disease showed the same significant predictors of grade 2 to 4 acute GVHD for CML; however, KPS and cytomegalovirus serostatus were not significant predictors for AML/ALL. Conclusion This analysis confirmed several previously reported risk factors for grade 2 to 4 acute GVHD. However, several new factors were identified whereas others are no longer significant. These new data may facilitate individualized risk estimates and raise several interesting biologic questions. C1 [Hahn, Theresa] Roswell Pk Canc Inst, Dept Med, Buffalo, NY 14263 USA. Med Coll Wisconsin, Milwaukee, WI 53226 USA. Univ Minnesota, Minneapolis, MN USA. Mayo Clin, Rochester, MN USA. Vanderbilt Univ, Nashville, TN USA. St Jude Childrens Hosp, Memphis, TN 38105 USA. Emory Univ, Atlanta, GA 30322 USA. Mt Sinai Med Ctr, New York, NY 10029 USA. Oregon Hlth & Sci Univ, Portland, OR 97201 USA. Leiden Univ, Med Ctr, Leiden, Netherlands. Princess Margaret Hosp, Toronto, ON M4X 1K9, Canada. Univ Basel Hosp, CH-4031 Basel, Switzerland. Florida Hosp, Inst Canc, Orlando, FL USA. Univ S Florida, H Lee Moffitt Canc Ctr, Tampa, FL 33682 USA. Univ Franche Comte, F-25030 Besancon, France. NCI, Bethesda, MD 20892 USA. Karolinska Univ Hosp, Stockholm, Sweden. RP Hahn, T (reprint author), Roswell Pk Canc Inst, Dept Med, Buffalo, NY 14263 USA. EM Theresa.hahn@roswellpark.org RI Halter, Joerg/C-9487-2012 FU American Society for Blood and Marrow Transplantation FX Support information appears in the Acknowledgment. American Society for Blood and Marrow Transplantation provided research support to T. H. NR 27 TC 86 Z9 88 U1 2 U2 4 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD DEC 10 PY 2008 VL 26 IS 35 BP 5728 EP 5734 DI 10.1200/JCO.2008.17.6545 PG 7 WC Oncology SC Oncology GA 381IC UT WOS:000261528200013 PM 18981462 ER PT J AU Dean, RM Fry, T Mackall, C Steinberg, SM Hakim, F Fowler, D Odom, J Foley, J Gress, R Bishop, MR AF Dean, Robert M. Fry, Terry Mackall, Crystal Steinberg, Seth M. Hakim, Fran Fowler, Daniel Odom, Jeanne Foley, Jason Gress, Ronald Bishop, Michael R. TI Association of Serum Interleukin-7 Levels With the Development of Acute Graft-Versus-Host Disease SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article ID BONE-MARROW-TRANSPLANTATION; STEM-CELL TRANSPLANTATION; PERIPHERAL-BLOOD; RISK-FACTORS; T-CELLS; IL-7; ENGRAFTMENT; DIFFERENTIATION; RECONSTITUTION; HOMEOSTASIS AB Purpose Morbidity from acute graft-versus-host disease (GVHD) limits the success of allogeneic hematopoietic stem-cell transplantation (HSCT) to treat malignancy. Interleukin-7 (IL-7), the principal homeostatic cytokine for T cells, is required for acute GVHD in murine models. In contrast to inflammatory cytokines (eg, IL-2, tumor necrosis factor alpha), IL-7 has not been studied extensively in the clinical transplant setting relative to its relationship with acute GVHD. Patients and Methods We evaluated the association of serum IL-7 levels with acute GVHD in 31 patients who were uniformly treated in a prospective clinical trial with reduced-intensity allogeneic HSCT from human leukocyte antigen-identical siblings. GVHD prophylaxis consisted of cyclosporine and methotrexate. Serum IL-7 levels and lymphocyte populations were determined at enrollment, the day of transplantation before the allograft infusion, and at specified intervals through 12 months post-transplantation. Results As expected, IL-7 levels were inversely correlated with T-cell populations (P < .00001). Acute GVHD was significantly associated with higher IL-7 levels at day +7 (P = .01) and day +14 (P = .00003) post-transplantation as well as with the allograft CD34(+) cell dose (P = .01). IL-7 levels at day +14 also correlated with the severity of acute GVHD (P < .0001). In logistic regression models, these factors were highly sensitive (up to 86%) and specific (100%) for classifying whether patients developed acute GVHD. Conclusion These data support preclinical observations that IL-7 plays a critical role in inducing acute GVHD and provide a rational basis for novel approaches to prevent and treat acute GVHD through modulation of the IL-7 pathway. C1 Cleveland Clin Fdn, Taussig Canc Inst, Cleveland, OH 44195 USA. [Bishop, Michael R.] NCI, Expt Transplantat & Immunol Branch, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. NCI, Pediat Oncol Branch, Bethesda, MD 20892 USA. NCI, Biostat & Data Management Sect, Bethesda, MD 20892 USA. RP Bishop, MR (reprint author), NCI, Expt Transplantat & Immunol Branch, Ctr Canc Res, NIH, Bldg 10-CRC,Room 4-3152,10 Ctr Dr, Bethesda, MD 20892 USA. EM mbishop@mail.nih.gov FU Center for Cancer Research; National Cancer Institute; National Institutes of Health FX Supported by the Intramural Research Program of the Center for Cancer Research, National Cancer Institute, National Institutes of Health. NR 31 TC 50 Z9 51 U1 0 U2 1 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD DEC 10 PY 2008 VL 26 IS 35 BP 5735 EP 5741 DI 10.1200/JCO.2008.17.1314 PG 7 WC Oncology SC Oncology GA 381IC UT WOS:000261528200014 PM 19001329 ER PT J AU Vale, C Tierney, JF Stewart, LA Brady, M Dinshaw, K Jakobsen, A Parmar, MKB Thomas, G Trimble, T Alberts, DS Chen, HW Cikaric, S Eifel, PJ Garipagaoglu, M Keys, H Kantardzic, N Lal, P Lanciano, R Leborgne, F Lorvidhaya, V Onishi, H Pearcey, RG Pras, E Roberts, K Rose, PG Thomas, G Whitney, CW AF Vale, Claire Tierney, Jayne F. Stewart, Lesley A. Brady, Mark Dinshaw, Ketayun Jakobsen, Anders Parmar, Mahesh K. B. Thomas, Gillian Trimble, Ted Alberts, David S. Chen, Hongwei Cikaric, Slobodan Eifel, Patricia J. Garipagaoglu, Melahat Keys, Henry Kantardzic, Nermina Lal, Punita Lanciano, Rachelle Leborgne, Felix Lorvidhaya, Vicharn Onishi, Hiroshi Pearcey, Robert G. Pras, Elizabeth Roberts, Kenneth Rose, Peter G. Thomas, Gillian Whitney, Charles W. CA Chemoradiotherapy Cervical Canc TI Reducing Uncertainties About the Effects of Chemoradiotherapy for Cervical Cancer: A Systematic Review and Meta-Analysis of Individual Patient Data From 18 Randomized Trials SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article ID GYNECOLOGIC-ONCOLOGY-GROUP; RADIATION-THERAPY; CONCURRENT CHEMOTHERAPY; PELVIC RADIATION; UTERINE CERVIX; RADICAL RADIOTHERAPY; ADVANCED-CARCINOMA; MITOMYCIN-C; CISPLATIN; INFUSION AB Background After a 1999 National Cancer Institute (NCI) clinical alert was issued, chemoradiotherapy has become widely used in treating women with cervical cancer. Two subsequent systematic reviews found that interpretation of the benefits was complicated, and some important clinical questions were unanswered. Patients and Methods We initiated a meta-analysis seeking updated individual patient data from all randomized trials to assess the effect of chemoradiotherapy on all outcomes. We prespecified analyses to investigate whether the effect of chemoradiotherapy differed by trial or patient characteristics. Results On the basis of 13 trials that compared chemoradiotherapy versus the same radiotherapy, there was a 6% improvement in 5-year survival with chemoradiotherapy (hazard ratio [HR] = 0.81, P < .001). A larger survival benefit was seen for the two trials in which chemotherapy was administered after chemoradiotherapy. There was a significant survival benefit for both the group of trials that used platinum-based (HR = 0.83, P = .017) and non-platinum-based (HR = 0.77, P < .009) chemoradiotherapy, but no evidence of a difference in the size of the benefit by radiotherapy or chemotherapy dose or scheduling was seen. Chemoradiotherapy also reduced local and distant recurrence and progression and improved disease-free survival. There was a suggestion of a difference in the size of the survival benefit with tumor stage, but not across other patient subgroups. Acute hematologic and GI toxicity was increased with chemoradiotherapy, but data were too sparse for an analysis of late toxicity. Conclusion These results endorse the recommendations of the NCI alert, but also demonstrate their applicability to all women and a benefit of non-platinum-based chemoradiotherapy. Furthermore, although these results suggest an additional benefit from adjuvant chemotherapy, this requires testing in randomized trials. C1 [Vale, Claire; Tierney, Jayne F.] Med Res Council Clin Trials Unit, Meta Anal Grp, London NW1 2DA, England. [Thomas, Gillian; Thomas, Gillian] Toronto Sunnybrook Canc Ctr, Toronto, ON, Canada. [Trimble, Ted] NCI, Therapy Evaluat Program, Bethesda, MD 20892 USA. [Alberts, David S.] Arizona Canc Ctr, Tucson, AZ USA. [Eifel, Patricia J.] Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA. [Keys, Henry] Albany Med Coll, Albany, NY 12208 USA. [Lanciano, Rachelle] Delaware Cty Mem Hosp, Drexel Hill, PA USA. [Lorvidhaya, Vicharn] Chiang Mai Univ, Chiang Mai, Thailand. [Onishi, Hiroshi] Univ Yamanashi, Yamanashi, Japan. [Pearcey, Robert G.] Cross Canc Inst, Edmonton, AB T6G 1Z2, Canada. [Pearcey, Robert G.] Univ Alberta, Edmonton, AB, Canada. [Pras, Elizabeth] Univ Med Ctr Groningen, Groningen, Netherlands. [Pras, Elizabeth] Univ Groningen, NL-9700 AB Groningen, Netherlands. [Roberts, Kenneth] Yale Univ, Sch Med, New Haven, CT USA. [Rose, Peter G.] Cleveland Clin, Cleveland, OH 44106 USA. [Whitney, Charles W.] Christiana Care Hlth Syst, Wilmington, DE USA. RP Vale, C (reprint author), Med Res Council Clin Trials Unit, Meta Anal Grp, 222 Euston Rd, London NW1 2DA, England. EM cv@ctu.mrc.ac.uk FU United Kingdom Medical Research Council; United Kingdom National Coordinating Centre for Research Capacity Development FX Supported by the United Kingdom Medical Research Council and the United Kingdom National Coordinating Centre for Research Capacity Development (C. V.). NR 52 TC 256 Z9 263 U1 0 U2 16 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD DEC 10 PY 2008 VL 26 IS 35 BP 5802 EP 5812 DI 10.1200/JCO.2008.16.4368 PG 11 WC Oncology SC Oncology GA 381IC UT WOS:000261528200024 ER PT J AU Yao, LS Vogeli, B Ying, JF Bax, A AF Yao, Lishan Voegeli, Beat Ying, Jinfa Bax, Ad TI NMR Determination of Amide N-H Equilibrium Bond Length from Concerted Dipolar Coupling Measurements SO JOURNAL OF THE AMERICAN CHEMICAL SOCIETY LA English DT Article ID RESIDUAL DIPOLAR; CONSERVATIVE MUTAGENESIS; BACKBONE DYNAMICS; PROTEIN-STRUCTURE; RELAXATION; UBIQUITIN; SPECTROSCOPY AB The N-H bond Length in backbone peptide groups of the protein GB3 has been studied by liquid-crystal NMR, using five structurally conserved mutants of this protein. In the absence of additional information, the impact of dynamic fluctuations of the N-H vector orientation on the (15)N-(1)H dipolar interaction cannot be separated from a change in N-H bond length. However, a change in N-H bond length directly impacts the orientation of C-H vectors in the peptide group, and simultaneous analysis of (13)C'-H(N) and (15)N-H(N) residual dipolar couplings, measured under five different alignment orientations, permits modelfree determination of the average equilibrium N-H bond length in GB3, yielding r(NH)(eq) = 1.008 +/- 0.006 angstrom. Anharmonicity of the bond stretching results in a slightly longer time-averaged bond length < r(NH)> = 1.015 +/- 0.006 angstrom, and an effective bond Length r(eff) = < r(NH)(-3)>(-1/3) = 1.023 +/- 0.006 angstrom pertinent for NMR relaxation analysis, not including the impact of zero-point or other angular fluctuations in N-H orientation. Using a reference frame defined by the backbone C degrees-C' vectors of the protein, angular fluctuations for N-H vectors in elements of secondary structure are approximately 1.5-fold larger for out-of-plane fluctuations than motions within the peptide plane and not much larger than anticipated on the basis of quantum mechanical analysis of their zero-point librations. C1 [Yao, Lishan; Voegeli, Beat; Ying, Jinfa; Bax, Ad] NIDDKD, Chem Phys Lab, NIH, Bethesda, MD 20892 USA. RP Bax, A (reprint author), NIDDKD, Chem Phys Lab, NIH, Bethesda, MD 20892 USA. EM bax@nih.gov RI Yao, Lishan /C-6961-2009; yao, lishan/H-3662-2012 OI yao, lishan/0000-0003-1797-922X FU NIDDK, NIH; NTH FX This work was supported in part by the Intramural Research Program of the NIDDK, NIH, and by the Intramural AIDS-Targeted Antiviral Program of the Office of the Director, NTH. We thank D.A. Torchia for useful discussions. NR 17 TC 61 Z9 61 U1 0 U2 15 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0002-7863 J9 J AM CHEM SOC JI J. Am. Chem. Soc. PD DEC 10 PY 2008 VL 130 IS 49 BP 16518 EP + DI 10.1021/ja805654f PG 4 WC Chemistry, Multidisciplinary SC Chemistry GA 406UK UT WOS:000263320200037 PM 19049453 ER PT J AU Yamanaka, S Zahanich, I Wersto, RP Boheler, KR AF Yamanaka, Satoshi Zahanich, Ihor Wersto, Robert P. Boheler, Kenneth R. TI Enhanced Proliferation of Monolayer Cultures of Embryonic Stem (ES) Cell-Derived Cardiomyocytes Following Acute Loss of Retinoblastoma SO PLOS ONE LA English DT Article AB Background: Cardiomyocyte (CM) cell cycle analysis has been impeded because of a reliance on primary neonatal cultures of poorly proliferating cells or chronic transgenic animal models with innate compensatory mechanisms. Methodology/Principal Findings: We describe an in vitro model consisting of monolayer cultures of highly proliferative embryonic stem (ES) cell-derived CM. Following induction with ascorbate and selection with puromycin, early CM cultures are >98% pure, and at least 85% of the cells actively proliferate. During the proliferative stage, cells express high levels of E2F3a, B-Myb and phosphorylated forms of retinoblastoma (Rb), but with continued cultivation, cells stop dividing and mature functionally. This developmental transition is characterized by a switch from slow skeletal to cardiac TnI, an increase in binucleation, cardiac calsequestrin and hypophosphorylated Rb, a decrease in E2F3, B-Myb and atrial natriuretic factor, and the establishment of a more negative resting membrane potential. Although previous publications suggested that Rb was not necessary for cell cycle control in heart, we find following acute knockdown of Rb that this factor actively regulates progression through the G1 checkpoint and that its loss promotes proliferation at the expense of CM maturation. Conclusions/Significance: We have established a unique model system for studying cardiac cell cycle progression, and show in contrast to previous reports that Rb actively regulates both cell cycle progression through the G1 checkpoint and maturation of heart cells. We conclude that this in vitro model will facilitate the analysis of cell cycle control mechanisms of CMs. C1 [Yamanaka, Satoshi; Zahanich, Ihor; Boheler, Kenneth R.] NIA, Cardiovasc Sci Lab, Baltimore, MD 21224 USA. [Wersto, Robert P.] NIA, NIH, Resource Res Branch, Bethesda, MD 20892 USA. RP Yamanaka, S (reprint author), NIA, Cardiovasc Sci Lab, Baltimore, MD 21224 USA. EM bohelerk@grc.nia.nih.gov FU Intramural Research Program of the NIH, National Institute on Aging FX This research was supported by the Intramural Research Program of the NIH, National Institute on Aging (KRB, RPW). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 70 TC 13 Z9 13 U1 0 U2 13 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 10 PY 2008 VL 3 IS 12 AR e3896 DI 10.1371/journal.pone.0003896 PG 15 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 436ZS UT WOS:000265455700006 PM 19066628 ER PT J AU Lusa, L Korn, EL McShane, LM AF Lusa, Lara Korn, Edward L. McShane, Lisa M. TI A class comparison method with filtering-enhanced variable selection for high-dimensional data sets SO STATISTICS IN MEDICINE LA English DT Article DE multiple testing methods; multivariate permutation methods; high-dimensional data; microarrays; variable filtering ID DIFFERENTIALLY EXPRESSED GENES; MICROARRAY EXPERIMENTS; BREAST-CANCER; LYMPHOCYTES; POPULATION; PROFILES AB High-throughput molecular analysis technologies can produce thousands of measurements for each of the assayed samples. A common scientific question is to identify the variables whose distribution differ between some pre-specified classes (i.e. are differentially expressed). The statistical cost of examining thousands of variables is related to the risk of identifying many variables that truly are not differentially expressed, and many different multiple testing strategies have been used for the analysis of high-dimensional data sets to control the number of these false positives. An approach that is often used in practice to reduce the multiple comparisons problem is to lessen the number of comparisons being performed by filtering out variables that are considered non-informative 'before' the analysis. However, deciding which and how many variables should be filtered out can be highly arbitrary, and different filtering strategies can result in different variables being identified as differentially expressed. We propose the filtering-enhanced variable selection (FEVS) method, a new multiple testin strategy for identifying differentially expressed variables. This method identifies differentially expressed variables by combining the results obtained using a variety of filtering methods, instead of using a pre-specified filtering method or trying to identify an optimal filtering of the variables prior to class comparison analysis. We prove that the FEVS method probabilistically controls the the number of false discoveries, and we show with a set of simulations and an example form the literature that FEVS can be useful for gaining sensitivity for the detection of truly differentially expressed variables. Published in 2008 by John Wiley & Sons. Ltd. C1 [Lusa, Lara] Univ Ljubljana, Dept Med Informat, Ljubljana 61000, Slovenia. [Korn, Edward L.; McShane, Lisa M.] NCI, Biometr Res Branch, Bethesda, MD 20892 USA. RP Lusa, L (reprint author), Univ Ljubljana, Dept Med Informat, Ljubljana 61000, Slovenia. EM Lara.Lusa@mf.uni-lj.si RI Lusa, Lara/C-6692-2015 OI Lusa, Lara/0000-0002-8981-2421 NR 22 TC 5 Z9 5 U1 0 U2 4 PU JOHN WILEY & SONS LTD PI CHICHESTER PA THE ATRIUM, SOUTHERN GATE, CHICHESTER PO19 8SQ, W SUSSEX, ENGLAND SN 0277-6715 J9 STAT MED JI Stat. Med. PD DEC 10 PY 2008 VL 27 IS 28 BP 5834 EP 5849 DI 10.1002/sim.3405 PG 16 WC Mathematical & Computational Biology; Public, Environmental & Occupational Health; Medical Informatics; Medicine, Research & Experimental; Statistics & Probability SC Mathematical & Computational Biology; Public, Environmental & Occupational Health; Medical Informatics; Research & Experimental Medicine; Mathematics GA 375VZ UT WOS:000261143200003 PM 18781559 ER PT J AU Cornwell, BR Carver, FW Coppola, R Johnson, L Alvarez, R Grillona, C AF Cornwell, Brian R. Carver, Frederick W. Coppola, Richard Johnson, Linda Alvarez, Ruben Grillona, Christian TI Evoked amygdala responses to negative faces revealed by adaptive MEG beamformers SO BRAIN RESEARCH LA English DT Article DE Adaptive beamformer; Amygdala; Anger; Facial expression; Fear; Magnetoencephalography ID SPATIALLY-FILTERED MAGNETOENCEPHALOGRAPHY; RECONSTRUCTING SPATIOTEMPORAL ACTIVITIES; HUMAN HIPPOCAMPAL; BRAIN; ACTIVATION; EMOTION; TASK; SYNCHRONIZATION; LATERALIZATION; RECOGNITION AB Adaptive beamformer analyses of magnetoencephalograms (MEG) have shown promise as a method for functional imaging of cortical processes. Although recent evidence is encouraging, it is unclear whether these methods can both localize and reconstruct the time course of activity in subcortical structures such as the amygdala. Fourteen healthy participants (7 women) performed a perceptual matching task of negative emotional faces (angry and fearful) and geometric shapes that was designed for functional magnetic resonance imaging (fMRI) studies to maximize amygdala activation. Neuromagnetic data were collected with a 275-channel whole-head magnetometer, and event-related adaptive beamformer analyses were conducted to estimate broadband evoked responses to faces and shapes across the whole brain in 7 mm steps. Group analyses revealed greater left amygdala. activity to faces over shapes, both when face-matching and shape-matching trials were presented in separate blocks and when they were randomly intermixed. This finding was replicated in a second experiment with 7 new participants (3 women). Virtual sensor time series showed clear evoked responses in the left amygdala. and left fusiform gyrus in both runs and experiments. We conclude that amygdala activity can be resolved from MEGs with adaptive beamformers with temporal resolution superior to other neuroimaging modalities. This demonstration should encourage the use of MEG for elucidating functional networks mediating fear-related neural phenomena that likely unfold rapidly in time across cortical and subcortical structures. Published by Elsevier B.V. C1 [Cornwell, Brian R.; Johnson, Linda; Alvarez, Ruben; Grillona, Christian] NIMH, Mood & Anxiety Disorders Program, NIH, Bethesda, MD 20892 USA. [Carver, Frederick W.; Coppola, Richard] NIMH, Magnetoencephalog Core Facil, NIH, Bethesda, MD 20892 USA. RP Cornwell, BR (reprint author), NIMH, Mood & Anxiety Disorders Program, NIH, 15 North Dr,MSC 2670, Bethesda, MD 20892 USA. EM cornwellb@mail.nih.gov FU National Institute of Mental Health FX This research was supported by the intramural research program at the National Institute of Mental Health. We would like to thank Arter Biggs for his assistance in obtaining MRIs from participants. We are grateful to Stephen Robinson (Neuromagnetism Laboratory, Department of Neurology, Henry Ford Hospital, Detroit, MI) for developing the SAMerf program that we used for event-related beamformer analysis. NR 38 TC 47 Z9 50 U1 1 U2 6 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0006-8993 J9 BRAIN RES JI Brain Res. PD DEC 9 PY 2008 VL 1244 BP 103 EP 112 DI 10.1016/j.brainres.2008.09.068 PG 10 WC Neurosciences SC Neurosciences & Neurology GA 384YH UT WOS:000261779600011 PM 18930036 ER PT J AU Kikuchi, J Kinoshita, I Shimizu, Y Oizumi, S Nishimura, M Birrer, MJ Dosaka-Akita, H AF Kikuchi, J. Kinoshita, I. Shimizu, Y. Oizumi, S. Nishimura, M. Birrer, M. J. Dosaka-Akita, H. TI Simultaneous blockade of AP-1 and phosphatidylinositol 3-kinase pathway in non-small cell lung cancer cells SO BRITISH JOURNAL OF CANCER LA English DT Article DE AP-1; phosphatidylinositol 3-kinase pathway; non-small cell lung cancer; LY294002; TAM67 ID ANCHORAGE-INDEPENDENT GROWTH; DOMINANT-NEGATIVE MUTANT; C-JUN; CYCLIN-A; UP-REGULATION; RAT1A CELLS; THERAPEUTIC STRATEGY; EPITHELIAL-CELLS; KINASE-ACTIVITY; RAT-1A CELLS AB c-Jun is a major constituent of AP-1 transcription factor that transduces multiple mitogen growth signals, and it is frequently overexpressed in non-small cell lung cancers (NSCLCs). Earlier, we showed that blocking AP-1 by the overexpression of a c-Jun dominant-negative mutant, TAM67, inhibited NSCLC cell growth. The phosphatidylinositol 3-kinase (PI3K)/Akt signal transduction pathway is important in transformation, proliferation, survival and metastasis of NSCLC cells. In this study, we used NCI-H1299 Tet-on clone cells that express TAM67 under the control of inducible promoter to determine the effects of inhibition of AP-1 and PI3K on cell growth. The PI3K inhibitor, LY294002, produced a dose-dependent inhibition of growth in H1299 cells and that inhibition was enhanced by TAM67. TAM67 increased dephosphorylation of Akt induced by LY294002 and reduced the TPA response element DNA-binding of phosphorylated c-Jun. TAM67 increased G1 cell cycle blockade induced by LY294002, which was partially associated with cyclin A decrease and p27(Kip1) accumulation. Furthermore, TAM67 and LY294002 act, at least additively, to inhibit anchorage-independent growth of the H1299 cells. These results suggest that AP-1 and PI3K/Akt pathways play an essential role in the growth of some NSCLC cells. C1 [Kinoshita, I.] Hokkaido Univ, Grad Sch Med, Dept Med Oncol, Kita Ku, Sapporo, Hokkaido 0608638, Japan. [Kikuchi, J.; Oizumi, S.; Nishimura, M.] Hokkaido Univ, Grad Sch Med, Dept Med 1, Sapporo, Hokkaido 0608638, Japan. [Birrer, M. J.] NCI, Cell & Canc Biol Branch, Bethesda, MD 20892 USA. RP Kinoshita, I (reprint author), Hokkaido Univ, Grad Sch Med, Dept Med Oncol, Kita Ku, North 15,West 7, Sapporo, Hokkaido 0608638, Japan. EM kinoshii@med.hokudai.ac.jp RI Shimizu, Yasushi/D-8057-2012; Akita, Hirotoshi/E-1356-2012; Nishimura, Masaharu/A-4062-2012 NR 45 TC 14 Z9 16 U1 0 U2 4 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0007-0920 J9 BRIT J CANCER JI Br. J. Cancer PD DEC 9 PY 2008 VL 99 IS 12 BP 2013 EP 2019 DI 10.1038/sj.bjc.6604782 PG 7 WC Oncology SC Oncology GA 382QI UT WOS:000261620100008 PM 19018257 ER PT J AU Frankel, DS Meigs, JB Massaro, JM Wilson, PWF O'Donnell, CJ D'Agostino, RB Tofler, GH AF Frankel, David S. Meigs, James B. Massaro, Joseph M. Wilson, Peter W. F. O'Donnell, Christopher J. D'Agostino, Ralph B. Tofler, Geoffrey H. TI Von Willebrand Factor, Type 2 Diabetes Mellitus, and Risk of Cardiovascular Disease The Framingham Offspring Study SO CIRCULATION LA English DT Article DE von Willebrand factor; diabetes mellitus; insulin resistance; cardiovascular diseases; epidemiology ID CORONARY-HEART-DISEASE; APPARENTLY HEALTHY-MEN; C-REACTIVE PROTEIN; FUTURE MYOCARDIAL-INFARCTION; EDINBURGH ARTERY; ENDOTHELIAL DYSFUNCTION; VONWILLEBRAND-FACTOR; PLASMA-CONCENTRATION; INSULIN-RESISTANCE; HEMOSTATIC MARKERS AB Background-Von Willebrand factor (vWF) is inconsistently associated with cardiovascular disease (CVD). This might be explained by associations of vWF with type 2 diabetes mellitus and insulin resistance. Methods and Results-We tested whether vWF predicted incident CVD in 3799 Framingham Offspring Study participants, and in particular, among those with type 2 diabetes mellitus or insulin resistance. During 11 years of follow-up, 351 participants developed CVD. In proportional hazards models (with adjustment for age, sex, blood pressure, smoking, body mass index, total and high-density lipoprotein cholesterol, and treatment with aspirin, insulin, antihypertensives, and lipid-lowering medications) with the lowest quartile of the vWF distribution as the referent, the hazard ratio (HR) for CVD was 0.94 in the second quartile, 0.98 in the third, and 1.32 in the highest (P = 0.04 for trend). Additional adjustment for type 2 diabetes mellitus or insulin resistance (homeostasis model) partially attenuated the association (multivariable HRs for top quartile 1.28 and 1.21, respectively). We then stratified the models by diabetes status or the homeostasis model of insulin resistance distribution (top quartile versus lower 3 quartiles). vWF was associated with CVD among participants with diabetes mellitus (HR for top quartile relative to bottom 1.47, P = 0.04 for trend) but not among nondiabetic participants (HR 1.15, P = 0.5) and similarly among insulin-resistant (HR 1.50, P = 0.01) but not insulin-sensitive (HR 1.02, P = 0.9) participants. Conclusions-Higher levels of vWF were associated with risk of CVD in people with type 2 diabetes mellitus or insulin resistance, which suggests that vWF may be a risk factor unique to these populations. (Circulation. 2008; 118: 2533-2539.) C1 [Meigs, James B.] Massachusetts Gen Hosp, Div Gen Med, Boston, MA 02114 USA. [O'Donnell, Christopher J.] Massachusetts Gen Hosp, Div Cardiol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. [Frankel, David S.] Univ Penn, Dept Med, Div Cardiovasc Med, Philadelphia, PA 19104 USA. [Massaro, Joseph M.; O'Donnell, Christopher J.; D'Agostino, Ralph B.] NHLBI, Framingham, MA USA. [Wilson, Peter W. F.] Emory Univ, Sch Med, Dept Med, Div Cardiol, Atlanta, GA USA. [Massaro, Joseph M.; D'Agostino, Ralph B.] Boston Univ, Dept Biostat, Boston, MA 02215 USA. [Tofler, Geoffrey H.] Royal N Shore Hosp, Sydney, NSW, Australia. RP Meigs, JB (reprint author), Massachusetts Gen Hosp, Div Gen Med, 50 Staniford St,9th Floor, Boston, MA 02114 USA. EM jmeigs@partners.org OI Massaro, Joseph/0000-0002-2682-4812 FU American Heart Association [92011960]; National Heart, Lung, and Blood Institute's Framingham Heart Study [N01-HC-25195] FX This study was supported by a Grant-in-Aid from the American Heart Association (No. 92011960 to Dr Massaro) and by the National Heart, Lung, and Blood Institute's Framingham Heart Study (contract No. N01-HC-25195). NR 49 TC 47 Z9 50 U1 0 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD DEC 9 PY 2008 VL 118 IS 24 BP 2533 EP 2539 DI 10.1161/CIRCULATIONAHA.108.792986 PG 7 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 381CJ UT WOS:000261512400008 PM 19029465 ER PT J AU Song, MH Aravind, L Muller-Reichert, T O'Connell, KF AF Song, Mi Hye Aravind, L. Mueller-Reichert, Thomas O'Connell, Kevin F. TI The Conserved Protein SZY-20 Opposes the Plk4-Related Kinase ZYG-1 to Limit Centrosome Size SO DEVELOPMENTAL CELL LA English DT Article ID DE-NOVO FORMATION; CAENORHABDITIS-ELEGANS; C-ELEGANS; CENTRIOLE DUPLICATION; PERICENTRIOLAR MATERIAL; DROSOPHILA SPD-2; VERTEBRATE CELLS; MESSENGER-RNAS; IN-VIVO; RECRUITMENT AB Microtubules are organized by the centrosome, a dynamic organelle that exhibits changes in both size and number during the cell cycle. Here we show that SZY-20, a putative RNA-binding protein, plays a critical role in limiting centrosome size in C. elegans. SZY-20 localizes in part to centrosomes and in its absence centrosomes possess increased levels of centriolar and pericentriolar components including gamma-tubulin and the centriole duplication factors ZYG-1 and SPD-2. These enlarged centrosomes possess normal centrioles, nucleate more microtubules, and fail to properly direct a number of microtubule-dependent processes. Depletion of ZYG-1 restores normal centrosome size and function to szy-20 mutants, whereas loss of szy-20 suppresses the centrosome duplication defects in both zyg-1 and spd-2 mutants. Our results describe a pathway that determines centrosome size and implicate centriole duplication factors in this process. C1 [Song, Mi Hye; O'Connell, Kevin F.] NIDDKD, Lab Biochem & Genet, NIH, Bethesda, MD 20894 USA. [Aravind, L.] Natl Lib Med, Natl Ctr Biotechnol Informat, NIH, Bethesda, MD 20894 USA. [Mueller-Reichert, Thomas] Max Planck Inst Mol Cell Biol & Genet MPI CBG, D-01307 Dresden, Germany. RP Song, MH (reprint author), NIDDKD, Lab Biochem & Genet, NIH, Bethesda, MD 20894 USA. EM mihyesong@mail.nih.gov; kevino@intra.niddk.nih.gov OI Song, Mi Hye/0000-0001-8326-6602 FU National Institutes Health (NIH); National Institute of Diabetes and Digestive and Kidney Diseases FX We thank So Jung Kim and O'Connell lab members for their support; David Weisblat, Andy Golden, Bob Goldstein, Nick Miliaras, and Nina Peel for comments on the manuscript; Harold Smith, Martin Srayko, Alexander Dammerman, Anion Audhya, Karen Oegema, Ken Kemphues, and Yuji Kohara for reagents; and In-Geol Choi and Kevin Eliceiri for technical assistance. Some strains were provided by The Caenorhabditis Genetics Center and The National Bioresource Project, Japan. This work was supported by the Intramural Research Program of the National Institutes Health (NIH) and by the National Institute of Diabetes and Digestive and Kidney Diseases. NR 45 TC 26 Z9 32 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 9 PY 2008 VL 15 IS 6 BP 901 EP 912 DI 10.1016/j.devcel.2008.09.018 PG 12 WC Cell Biology; Developmental Biology SC Cell Biology; Developmental Biology GA 382US UT WOS:000261631500013 PM 19081077 ER PT J AU Ottman, R Rosenberger, L Bagic, A Kamberakis, K Ritzl, EK Wohlschlager, AM Shamim, S Sato, S Liew, C Gaillard, WD Wiggs, E Berl, MM Reeves-Tyers, P Baker, EH Butman, JA Theodore, WH AF Ottman, R. Rosenberger, L. Bagic, A. Kamberakis, K. Ritzl, E. K. Wohlschlager, A. M. Shamim, S. Sato, S. Liew, C. Gaillard, W. D. Wiggs, E. Berl, M. M. Reeves-Tyers, P. Baker, E. H. Butman, J. A. Theodore, W. H. TI Altered language processing in autosomal dominant partial epilepsy with auditory features SO NEUROLOGY LA English DT Article ID TEMPORAL-LOBE EPILEPSY; IDIOPATHIC PARTIAL EPILEPSY; SPORADIC PARTIAL EPILEPSY; APHASIC SEIZURES; LGI1 MUTATIONS; TOPIRAMATE TREATMENT; CHROMOSOME 10Q; FUNCTIONAL MRI; GENE; FAMILIES AB Background: Autosomal dominant partial epilepsy with auditory features (ADPEAF) is an idiopathic focal epilepsy syndrome with auditory symptoms or receptive aphasia as major ictal manifestations, frequently associated with mutations in the leucine-rich, glioma inactivated 1 (LGI1) gene. Although affected subjects do not have structural abnormalities detected on routine MRI, a lateral temporal malformation was identified through high resolution MRI in one family. We attempted to replicate this finding and to assess auditory and language processing in ADPEAF using fMRI and magnetoencephalography (MEG). Methods: We studied 17 subjects (10 affected mutation carriers, 3 unaffected carriers, 4 noncarriers) in 7 ADPEAF families, each of which had a different LGI1 mutation. Subjects underwent high-resolution structural MRI, fMRI with an auditory description decision task (ADDT) and a tone discrimination task, and MEG. A control group comprising 26 volunteers was also included. Results: We found no evidence of structural abnormalities in any of the 17 subjects. On fMRI with ADDT, subjects with epilepsy had significantly less activation than controls. On MEG with auditory stimuli, peak 2 auditory evoked field latency was significantly delayed in affected individuals compared to controls. Conclusions: These findings do not support the previous report of a lateral temporal malformation in autosomal dominant partial epilepsy with auditory features (ADPEAF). However, our fMRI and magnetoencephalography data suggest that individuals with ADPEAF have functional impairment in language processing. Neurology (R) 2008;71:1973-1980 C1 [Ottman, R.; Kamberakis, K.] Columbia Univ, GH Sergievsky Ctr, New York, NY 10032 USA. [Ottman, R.; Kamberakis, K.] Columbia Univ, Dept Epidemiol, New York, NY 10032 USA. [Ottman, R.] Columbia Univ, Dept Neurol, New York, NY 10032 USA. [Ottman, R.] New York State Psychiat Inst & Hosp, New York, NY 10032 USA. [Rosenberger, L.; Bagic, A.; Ritzl, E. K.; Wohlschlager, A. M.; Shamim, S.; Gaillard, W. D.; Wiggs, E.; Reeves-Tyers, P.; Theodore, W. H.] NINDS, Clin Epidemiol Sect, Bethesda, MD 20892 USA. [Bagic, A.; Sato, S.] NINDS, EEG Sect, Bethesda, MD 20892 USA. [Berl, M. M.] George Washington Univ, Sch Med, Childrens Natl Med Ctr, Dept Neurosci, Washington, DC USA. [Baker, E. H.; Butman, J. A.] NIH, Dept Diagnost Radiol, Bethesda, MD 20892 USA. RP Ottman, R (reprint author), Columbia Univ, GH Sergievsky Ctr, 630 W 168th St,P&S Box 16, New York, NY 10032 USA. EM ro6@columbia.edu RI Butman, John/A-2694-2008; Ottman, Ruth/O-2371-2013; OI Butman, John/0000-0002-1547-9195 FU NIH [R01NS036319, R01NS043472]; NINDS Division of Intramural Research FX Supported by NIH grants R01NS036319 and R01NS043472 (to R.O.), and the NINDS Division of Intramural Research. NR 39 TC 12 Z9 13 U1 1 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0028-3878 J9 NEUROLOGY JI Neurology PD DEC 9 PY 2008 VL 71 IS 24 BP 1973 EP 1980 DI 10.1212/01.wnl.0000336923.29538.5b PG 8 WC Clinical Neurology SC Neurosciences & Neurology GA 381CN UT WOS:000261512900008 PM 19064878 ER PT J AU Kagaayi, J Gray, RH Brahmbhatt, H Kigozi, G Nalugoda, F Wabwire-Mangen, F Serwadda, D Sewankambo, N Ddungu, V Ssebagala, D Sekasanvu, J Kigozi, G Makumbi, F Kiwanuka, N Lutalo, T Reynolds, SJ Wawer, MJ AF Kagaayi, Joseph Gray, Ronald H. Brahmbhatt, Heena Kigozi, Godfrey Nalugoda, Fred Wabwire-Mangen, Fred Serwadda, David Sewankambo, Nelson Ddungu, Veronica Ssebagala, Darix Sekasanvu, Joseph Kigozi, Grace Makumbi, Fredrick Kiwanuka, Noah Lutalo, Tom Reynolds, Steven J. Wawer, Maria J. TI Survival of Infants Born to HIV-Positive Mothers, by Feeding Modality, in Rakai, Uganda SO PLOS ONE LA English DT Article AB Background: Data comparing survival of formula-fed to breast-fed infants in programmatic settings are limited. We compared mortality and HIV-free of breast and formula-fed infants born to HIV-positive mothers in a program in rural, Rakai District Uganda. Methodology/Principal Findings: One hundred eighty two infants born to HIV-positive mothers were followed at one, six and twelve months postpartum. Mothers were given infant-feeding counseling and allowed to make informed choices as to whether to formula-feed or breast-feed. Eligible mothers and infants received antiretroviral therapy (ART) if indicated. Mothers and their newborns received prophylaxis for prevention of mother-to-child HIV transmission (pMTCT) if they were not receiving ART. Infant HIV infection was detected by PCR (Roche Amplicor 1.5) during the follow-up visits. Kaplan Meier time-to-event methods were used to compare mortality and HIV-free survival. The adjusted hazard ratio (Adjusted HR) of infant HIV-free survival was estimated by Cox regression. Seventy-five infants (41%) were formula-fed while 107 (59%) were breast-fed. Exclusive breast-feeding was practiced by only 25% of breast-feeding women at one month postpartum. The cumulative 12-month probability of infant mortality was 18% (95% CI = 11%-29%) among the formula-fed compared to 3% (95% CI = 1%-9%) among the breast-fed infants (unadjusted hazard ratio (HR) = 6.1(95% CI = 1.7-21.4, P-value<0.01). There were no statistically significant differentials in HIV-free survival by feeding choice (86% in the formula-fed compared to 96% in breast-fed group (Adjusted RH = 2.8[ 95% CI = 0.67-11.7, P-value = 0.16] Conclusions/Significance: Formula-feeding was associated with a higher risk of infant mortality than breastfeeding in this rural population. Our findings suggest that formula-feeding should be discouraged in similar African settings. C1 [Kigozi, Godfrey; Nalugoda, Fred; Ddungu, Veronica] Rakai Hlth Sci Program, Dept Clin Res Studies, Entebbe, Uganda. [Gray, Ronald H.; Brahmbhatt, Heena; Wawer, Maria J.] Johns Hopkins Univ, Bloomberg Sch Publ Hlth, Dept Populat, Family & Reproduct Hlth, Baltimore, MD 21218 USA. [Wabwire-Mangen, Fred; Makumbi, Fredrick; Kiwanuka, Noah] Makerere Univ, Sch Publ Hlth, Dept Epidemiol & Biostat, Kampala, Uganda. [Serwadda, David] Makerere Univ, Sch Publ Hlth, Dept Dis Control, Kampala, Uganda. [Sewankambo, Nelson] Makerere Univ, Sch Med, Dept Med, Clin Epidemiol Unit, Kampala, Uganda. [Ssebagala, Darix; Sekasanvu, Joseph; Lutalo, Tom] Rakai Hlth Sci Program, Dept Biostat & Data Management, Entebbe, Uganda. [Kigozi, Grace] Rakai Hlth Sci Program, Dept Quality Control & Quality Assurance, Entebbe, Uganda. [Reynolds, Steven J.] Johns Hopkins Univ, Sch Med, Div Infect Dis, Baltimore, MD 21218 USA. [Reynolds, Steven J.] NIAID, NIH, Div Intramural Res, Lab Immunoregulat, Bethesda, MD USA. RP Kagaayi, J (reprint author), Rakai Hlth Sci Program, Dept Clin Res Studies, Entebbe, Uganda. EM jkagayi@rhsp.org OI Sewankambo, Nelson/0000-0001-9362-053X FU National Institute of Child Health and Human Development(NICHD); Presidential Emergency Plan for AIDS Relief(PEPFAR) FX National Institute of Child Health and Human Development(NICHD). Presidential Emergency Plan for AIDS Relief(PEPFAR). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 18 TC 43 Z9 43 U1 1 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 9 PY 2008 VL 3 IS 12 AR e3877 DI 10.1371/journal.pone.0003877 PG 7 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 436ZP UT WOS:000265455200003 PM 19065270 ER PT J AU Malone, JH Fontenot, BE AF Malone, John H. Fontenot, Brian E. TI Patterns of Reproductive Isolation in Toads SO PLOS ONE LA English DT Article ID FROG RANA-RUGOSA; HALDANES RULE; POSTZYGOTIC ISOLATION; HYBRID INVIABILITY; CHARACTER DISPLACEMENT; HETEROGAMETIC SEX; GENE-EXPRESSION; MOLECULAR SYSTEMATICS; CENTRARCHID FISHES; DARWINS COROLLARY AB Understanding the general features of speciation is an important goal in evolutionary biology, and despite significant progress, several unresolved questions remain. We analyzed an extensive comparative dataset consisting of more than 1900 crosses between 92 species of toads to infer patterns of reproductive isolation. This unique dataset provides an opportunity to examine the strength of reproductive isolation, the development and sex ratios of hybrid offspring, patterns of fertility and infertility, and polyploidization in hybrids all in the context of genetic divergence between parental species. We found that the strength of intrinsic postzygotic isolation increases with genetic divergence, but relatively high levels of divergence are necessary before reproductive isolation is complete in toads. Fertilization rates were not correlated to genetic divergence, but hatching success, the number of larvae produced, and the percentage of tadpoles reaching metamorphosis were all inversely related with genetic divergence. Hybrids between species with lower levels of divergence developed to metamorphosis, while hybrids with higher levels of divergence stopped developing in gastrula and larval stages. Sex ratios of hybrid offspring were biased towards males in 70% of crosses and biased towards females in 30% of crosses. Hybrid females from crosses between closely related species were completely fertile, while approximately half (53%) of hybrid males were sterile, with sterility predicted by genetic divergence. The degree of abnormal ploidy in hybrids was positively related to genetic divergence between parental species, but surprisingly, polyploidization had no effect on patterns of asymmetrical inviability. We discuss explanations for these patterns, including the role of Haldane's rule in toads and anurans in general, and suggest mechanisms generating patterns of reproductive isolation in anurans. C1 [Malone, John H.; Fontenot, Brian E.] Univ Texas, Dept Biol, Arlington, TX USA. RP Malone, JH (reprint author), NIDDKD, Cellular & Dev Biol Lab, NIH, Dept Hlth & Human Serv, Bethesda, MD 20892 USA. EM malonej@niddk.nih.gov NR 89 TC 34 Z9 35 U1 1 U2 9 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 9 PY 2008 VL 3 IS 12 AR e3900 DI 10.1371/journal.pone.0003900 PG 11 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 436ZP UT WOS:000265455200012 PM 19065271 ER PT J AU Manji, H McEwen, BS AF Manji, Husseini McEwen, Bruce S. TI Reply to Schmidt et al.: The long and the short of BAG1 SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Editorial Material ID GLUCOCORTICOID-RECEPTOR C1 [McEwen, Bruce S.] Rockefeller Univ, New York, NY 10021 USA. [Manji, Husseini] NIMH, Mood & Anxiety Disorders Program, Bethesda, MD 20892 USA. RP McEwen, BS (reprint author), Rockefeller Univ, 1230 York Ave, New York, NY 10021 USA. EM mcewen@mail.rockefeller.edu NR 4 TC 0 Z9 0 U1 0 U2 0 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 9 PY 2008 VL 105 IS 49 BP E102 EP E102 DI 10.1073/pnas.0810014105 PG 1 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 383XB UT WOS:000261706600102 ER PT J AU Jiang, BM Gentsch, JR Glass, RI AF Jiang, Baoming Gentsch, Jon R. Glass, Roger I. TI Inactivated rotavirus vaccines: A priority for accelerated vaccine development SO VACCINE LA English DT Review DE Rotavirus; Vaccine; Parenteral; Intussusception ID VIRUS-LIKE PARTICLES; PROTECTIVE IMMUNITY; GNOTOBIOTIC PIGS; INTRAMUSCULAR IMMUNIZATION; ANTIBODIES; MICE; GASTROENTERITIS; IMMUNOGENICITY; EFFICACY; SAFETY AB Live oral rotavirus vaccines have proven to be generally safe and effective to prevent severe dehydrating diarrhea among children in high and some middle income countries. However, concerns linger about rare but severe adverse events, Such as intussusception and their efficacy against the full range of rotavirus serotypes. More importantly, live oral vaccines have been less immunogenic and results of trails to assess their efficacy in poor children of both Africa and Asia will not be available for 2-3 years. This review describes the rationale for developing an inactivated rotavirus vaccine (IRV) as ail alternative approach should live oral vaccines not work well in these challenging populations. Studies have demonstrated the protective role of serum antibody in animals and children and the robust serum antibody response and protection against rotavirus infection in animal models following parenteral immunization with IRV. Four years after licensing the first new generation of rotavirus vaccine, we still remain several years away from knowing how well they work in the target populations. Research to develop alternative approaches should be fostered as an insurance policy to protect against suboptimal efficacy of Unanticipated adverse events that Could hinder global immunization and protection of all children. Published by Elsevier Ltd. C1 [Jiang, Baoming; Gentsch, Jon R.; Glass, Roger I.] Ctr Dis Control & Prevent, Div Viral Dis, Atlanta, GA USA. [Glass, Roger I.] NIH, Fogarty Int Ctr, Bethesda, MD USA. RP Jiang, BM (reprint author), Natl Ctr Immunizat & Resp Dis, Gastroenteritis & Resp Viruses Lab Branch, Mailstop G04,1600 Clifton Rd, Atlanta, GA 30333 USA. EM bxj4@cdc.gov NR 38 TC 32 Z9 36 U1 0 U2 1 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0264-410X J9 VACCINE JI Vaccine PD DEC 9 PY 2008 VL 26 IS 52 BP 6754 EP 6758 DI 10.1016/j.vaccine.2008.10.008 PG 5 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA 386QT UT WOS:000261898400007 PM 18951937 ER EF