FN Thomson Reuters Web of Science™ VR 1.0 PT J AU Hambright, D Park, KY Brooks, M McKay, R Swaroop, A Nasonkin, IO AF Hambright, Dustin Park, Kye-Yoon Brooks, Matthew McKay, Ron Swaroop, Anand Nasonkin, Igor O. TI Long-term survival and differentiation of retinal neurons derived from human embryonic stem cell lines in un-immunosuppressed mouse retina SO MOLECULAR VISION LA English DT Article ID HUMAN NEURAL PROGENITORS; NEUROTROPHIC FACTOR; PHOTORECEPTOR DEGENERATION; SUBRETINAL SPACE; PARKINSONS-DISEASE; CHONDROITINASE ABC; PRECURSOR CELLS; GROWTH-FACTORS; HOST RETINA; RAT MODEL AB Purpose: To examine the potential of NIH-maintained human embryonic stem cell (hESC) lines TE03 and UC06 to differentiate into retinal progenitor cells (hESC-RPCs) using the noggin/Dkk-1/IGF-1/FGF9 protocol. An additional goal is to examine the in vivo dynamics of maturation and retinal integration of subretinal and epiretinal (vitreous space) hESC-RPC grafts without immunosuppression. Methods: hESCs were neuralized in vitro with noggin for 2 weeks and expanded to derive neuroepithelial cells (hESC-neural precursors, NPs). Wnt (Integration 1 and wingless) blocking morphogens Dickkopf-1 (Dkk-1) and Insulin-like growth factor 1 (IGF-1) were used to direct NPs to a rostral neural fate, and fibroblast growth factor 9 (FGF9)/fibroblast growth factor-basic (bFGF) were added to bias the differentiation of developing anterior neuroectoderm cells to neural retina (NR) rather than retinal pigment epithelium (RPE). Cells were dissociated and grafted into the subretinal and epiretinal space of young adult (4-6-week-old) mice (C57BL/6J x129/Sv mixed background). Remaining cells were replated for (i) immunocytochemical analysis and (ii) used for quantitative reverse transcription polymerase chain reaction (qRT-PCR) analysis. Mice were sacrificed 3 weeks or 3 months after grafting, and the grafts were examined by histology and immunohistochemistry for survival of hESC-RPCs, presence of mature neuronal and retinal markers, and the dynamics of in vivo maturation and integration into the host retina. Results: At the time of grafting, hESC-RPCs exhibited immature neural/neuronal immunophenotypes represented by nestin and neuronal class III beta-tubulin, with about half of the cells positive for cell proliferation marker Kiel University raised antibody number 67 (Ki67), and no recoverin-positive (recoverin [+]) cells. The grafted cells expressed eye field markers paired box 6 (PAX6), retina and anterior neural fold homeobox (RAX), sine oculis homeobox homolog 6 (SIX6), LIM homeobox 2 (LHX2), early NR markers (Ceh-10 homeodomain containing homolog [CHX10], achaete-scute complex homolog 1 [MASH1], mouse atonal homolog 5 [MATH5], neurogenic differentiation 1 [NEUROD1]), and some retinal cell fate markers (brain-specific homeobox/POU domain transcription factor 3B [BRN3B], prospero homeobox 1 [PROX1], and recoverin). The cells in the subretinal grafts matured to predominantly recoverin [+] phenotype by 3 months and survived in a xenogenic environment without immunosuppression as long as the blood-retinal barrier was not breached by the transplantation procedure. The epiretinal grafts survived but did not express markers of mature retinal cells. Retinal integration into the retinal ganglion cell (RGC) layer and the inner nuclear layer (INL) was efficient from the epiretinal but not subretinal grafts. The subretinal grafts showed limited ability to structurally integrate into the host retina and only in cases when NR was damaged during grafting. Only limited synaptogenesis and no tumorigenicity was observed in grafts. Conclusions: Our studies show that (i) immunosuppression is not mandatory to xenogenic graft survival in the retina, (ii) the subretinal but not the epiretinal niche can promote maturation of hESC-RPCs to photoreceptors, and (iii) the hESC-RPCs from epiretinal but not subretinal grafts can efficiently integrate into the RGC layer and INL. The latter could be of value for long-lasting neuroprotection of retina in some degenerative conditions and glaucoma. Overall, our results provide new insights into the technical aspects associated with cell-based therapy in the retina. C1 [Hambright, Dustin; Brooks, Matthew; Swaroop, Anand; Nasonkin, Igor O.] NEI, N NRL, NIH, Bethesda, MD 20892 USA. [Park, Kye-Yoon; McKay, Ron] Natl Inst Neurol Disorders & Stroke, Mol Biol Lab, NIH, Bethesda, MD USA. [Park, Kye-Yoon; McKay, Ron] Natl Inst Neurol Disorders & Stroke, NIH Stem Cell Unit, NIH, Bethesda, MD USA. RP Nasonkin, IO (reprint author), NEI, N NRL, NIH, 6 Ctr Dr,MSC0610,Bldg 6,Room 341, Bethesda, MD 20892 USA. EM nasonkini@mail.nih.gov OI Swaroop, Anand/0000-0002-1975-1141 FU National Eye Institute (NEI); National Institute of Neurologic Disorders and Stroke (NINDS) FX This research was supported by intramural programs of the National Eye Institute (NEI) and National Institute of Neurologic Disorders and Stroke (NINDS). We are grateful to Dr. Ginger Tansey (NEI) for help with experimental animals, Dr. Robert Fariss for help with confocal microscopy and Dr. Jacob Nellissery for help with selecting the antibodies. We thank the members of N-NRL laboratory for discussion of our results, and especially Dr. James Friedman for carefully reading the manuscript. NR 78 TC 37 Z9 39 U1 0 U2 9 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 APR 12 PY 2012 VL 18 IS 96-97 BP 920 EP 936 PG 17 WC Biochemistry & Molecular Biology; Ophthalmology SC Biochemistry & Molecular Biology; Ophthalmology GA 947NJ UT WOS:000304436400001 PM 22539871 ER PT J AU Lickwar, CR Mueller, F Hanlon, SE McNally, JG Lieb, JD AF Lickwar, Colin R. Mueller, Florian Hanlon, Sean E. McNally, James G. Lieb, Jason D. TI Genome-wide protein-DNA binding dynamics suggest a molecular clutch for transcription factor function SO NATURE LA English DT Article ID GLUCOCORTICOID-RECEPTOR; EUKARYOTIC GENOME; BUDDING YEAST; LIVING CELLS; CHROMATIN; PROMOTER; EQUILIBRIUM; MECHANISM; EXCHANGE; SITES AB Dynamic access to genetic information is central to organismal development and environmental response. Consequently, genomic processes must be regulated by mechanisms that alter genome function relatively rapidly(1-4). Conventional chromatin immunoprecipitation (ChIP) experiments measure transcription factor occupancy(5), but give no indication of kinetics and are poor predictors of transcription factor function at a given locus. To measure transcription-factor-binding dynamics across the genome, we performed competition ChIP (refs 6, 7) with a sequence-specific Saccharomyces cerevisiae transcription factor, Rap1 (ref. 8). Rap1-binding dynamics and Rap1 occupancy were only weakly correlated (R-2 = 0.14), but binding dynamics were more strongly linked to function than occupancy. Long Rap1 residence was coupled to transcriptional activation, whereas fast binding turnover, which we refer to as 'treadmilling', was linked to low transcriptional output. Thus, DNA-binding events that seem identical by conventional ChIP may have different underlying modes of interaction that lead to opposing functional outcomes. We propose that transcription factor binding turnover is a major point of regulation in determining the functional consequences of transcription factor binding, and is mediated mainly by control of competition between transcription factors and nucleosomes. Our model predicts a clutch-like mechanism that rapidly engages a treadmilling transcription factor into a stable binding state, or vice versa, to modulate transcription factor function. C1 [Lickwar, Colin R.; Hanlon, Sean E.; Lieb, Jason D.] Univ N Carolina, Lineberger Comprehens Canc Ctr, Curriculum Genet & Mol Biol, Dept Biol,Carolina Ctr Genome Sci, Chapel Hill, NC 27599 USA. [Mueller, Florian; McNally, James G.] NCI, LRBGE, NIH, Bethesda, MD 20892 USA. [Mueller, Florian] Ctr Natl Rech Sci, Inst Pasteur, Grp Imagerie & Modelisat, Unite Rech Associee 2582, F-75015 Paris, France. RP Lieb, JD (reprint author), Univ N Carolina, Lineberger Comprehens Canc Ctr, Curriculum Genet & Mol Biol, Dept Biol,Carolina Ctr Genome Sci, CB 3280,408 Fordham Hall, Chapel Hill, NC 27599 USA. EM jlieb@bio.unc.edu RI Mueller, Florian/C-9075-2012 OI Mueller, Florian/0000-0002-9622-4396 FU US National Institutes of Health (NIH) [R01-GM072518]; NIH, National Cancer Institute, Center for Cancer Research; Region Ile-de-France in the framework of C'Nano IdF, the nanoscience competence center of Paris Region FX We thank T. Kaplan and O. Rando for help with their turnover model, T. Palpant and S. Adar for help with time course experiments, and A. Leonardo Iniguez and H. Rosenbaum of Roche Nimblegen for pre-release custom HD4 12-plex microarrays. This work was supported by the US National Institutes of Health (NIH) Grant R01-GM072518 (to J.D.L.), and the intramural program of the NIH, National Cancer Institute, Center for Cancer Research (to J.G.M. and F.M.). F.M. was also supported in part by the Region Ile-de-France in the framework of C'Nano IdF, the nanoscience competence center of Paris Region. NR 38 TC 105 Z9 107 U1 1 U2 34 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0028-0836 J9 NATURE JI Nature PD APR 12 PY 2012 VL 484 IS 7393 BP 251 EP U141 DI 10.1038/nature10985 PG 7 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 930OV UT WOS:000303149900037 PM 22498630 ER PT J AU Ishaq, M Lin, BR Bosche, M Zheng, X Yang, J Huang, DW Lempicki, RA Aguilera-Gutierrez, A Natarajan, V AF Ishaq, Mohammad Lin, Bor-Ruei Bosche, Marjorie Zheng, Xin Yang, Jun Huang, Dawei Lempicki, Richard A. Aguilera-Gutierrez, Angelica Natarajan, Ven TI LIM kinase 1 - dependent cofilin 1 pathway and actin dynamics mediate nuclear retinoid receptor function in T lymphocytes (vol 12, 41, 2011) SO BMC MOLECULAR BIOLOGY LA English DT Correction C1 [Ishaq, Mohammad; Lin, Bor-Ruei; Aguilera-Gutierrez, Angelica; Natarajan, Ven] NCI, Mol Cell Biol Lab, SAIC Frederick, Frederick, MD 21702 USA. [Bosche, Marjorie; Zheng, Xin; Yang, Jun; Huang, Dawei; Lempicki, Richard A.] NCI, Lab Immunopathogenesis & Bioinformat, SAIC Frederick, Frederick, MD 21702 USA. RP Ishaq, M (reprint author), NCI, Mol Cell Biol Lab, SAIC Frederick, Frederick, MD 21702 USA. EM mishaq@mail.nih.gov RI Lempicki, Richard/E-1844-2012 OI Lempicki, Richard/0000-0002-7059-409X 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 1471-2199 J9 BMC MOL BIOL JI BMC Mol. Biol. PD APR 12 PY 2012 VL 13 AR 14 DI 10.1186/1471-2199-13-14 PG 1 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 939NK UT WOS:000303818100001 ER PT J AU Abdollahpour, H Appaswamy, G Kotlarz, D Diestelhorst, J Beier, R Schaffer, AA Gertz, EM Schambach, A Kreipe, HH Pfeifer, D Engelhardt, KR Rezaei, N Grimbacher, B Lohrmann, S Sherkat, R Klein, C AF Abdollahpour, Hengameh Appaswamy, Giridharan Kotlarz, Daniel Diestelhorst, Jana Beier, Rita Schaeffer, Alejandro A. Gertz, E. Michael Schambach, Axel Kreipe, Hans H. Pfeifer, Dietmar Engelhardt, Karin R. Rezaei, Nima Grimbacher, Bodo Lohrmann, Sabine Sherkat, Roya Klein, Christoph TI The phenotype of human STK4 deficiency SO BLOOD LA English DT Article ID ORGAN SIZE CONTROL; CONGENITAL NEUTROPENIA; OXIDATIVE-STRESS; CASPASE CLEAVAGE; KINASE MST1; APOPTOSIS; PHOSPHORYLATION; ACTIVATION; MUTATIONS; PATHWAY AB We describe a novel clinical phenotype associating T- and B-cell lymphopenia, intermittent neutropenia, and atrial septal defects in 3 members of a consanguineous kindred. Their clinical histories included recurrent bacterial infections, viral infections, mucocutaneous candidiasis, cutaneous warts, and skin abscesses. Homozygosity mapping and candidate gene sequencing revealed a homozygous premature termination mutation in the gene STK4 (serine threonine kinase 4, formerly having the symbol MST1). STK4 is the human ortholog of Drosophila Hippo, the central constituent of a highly conserved pathway controlling cell growth and apoptosis. STK4-deficient lymphocytes and neutrophils exhibit enhanced loss of mitochondrial membrane potential and increased susceptibility to apoptosis. STK4 deficiency is a novel human primary immunodeficiency syndrome. (Blood. 2012; 119(15):3450-3457) C1 [Kotlarz, Daniel; Diestelhorst, Jana; Klein, Christoph] Dr von Haunersches Kinderspital, Univ Childrens Hosp Munich, D-80337 Munich, Germany. [Abdollahpour, Hengameh; Appaswamy, Giridharan; Kotlarz, Daniel; Diestelhorst, Jana; Beier, Rita; Klein, Christoph] Hannover Med Sch, Dept Pediat Hematol Oncol, D-3000 Hannover, Germany. [Schaeffer, Alejandro A.; Gertz, E. Michael] NIH, Natl Ctr Biotechnol Informat, Dept Hlth & Human Serv, Bethesda, MD 20892 USA. [Schambach, Axel] Hannover Med Sch, Dept Expt Hematol, D-3000 Hannover, Germany. [Kreipe, Hans H.] Hannover Med Sch, Inst Pathol, D-3000 Hannover, Germany. [Pfeifer, Dietmar] Univ Freiburg, Med Ctr, Dept Hematol Oncol, Core Facil Genom 2, Freiburg, Germany. [Engelhardt, Karin R.; Grimbacher, Bodo] Royal Free Hosp, Dept Immunol & Mol Pathol, London NW3 2QG, England. [Engelhardt, Karin R.; Grimbacher, Bodo] UCL, London, England. [Rezaei, Nima] Univ Tehran Med Sci, Childrens Med Ctr, Pediat Ctr Excellence, Res Ctr Immunodeficiencies, Tehran, Iran. [Lohrmann, Sabine] Hannover Med Sch, Dept Pediat Cardiol, D-3000 Hannover, Germany. [Sherkat, Roya] Isfahan Univ Med Sci, Dept Infect Dis, Infect Dis Res Ctr, Esfahan, Iran. RP Klein, C (reprint author), Dr von Haunersches Kinderspital, Univ Childrens Hosp Munich, Lindwurmstr 4, D-80337 Munich, Germany. EM christoph.klein@med.uni-muenchen.de RI Schaffer, Alejandro/F-2902-2012; Rezaei, Nima/B-4245-2008; OI Rezaei, Nima/0000-0002-3836-1827; Gertz, E. Michael/0000-0001-8390-4387 FU Deutsche Forschungsgemeinschaft [SFB900, KFO250]; Care-for-Rare Foundation; Deutsche Jose Carreras Leukamie-Stiftung; European Union commission [MEXT-CT-2006-042316, FP7/2007-2013]; EURO-PADnet [HEALTH-F2-2008-201549]; National Institutes of Health, National Library of Medicine FX This work was supported by the Deutsche Forschungsgemeinschaft (SFB900, KFO250, and Gottfried-Wilhelm-Leibniz program), the Care-for-Rare Foundation, the Deutsche Jose Carreras Leukamie-Stiftung, the European Union commission Marie-Curie (grants MEXT-CT-2006-042316 and FP7/2007-2013), EURO-PADnet (grant HEALTH-F2-2008-201549), and in part by the Intramural Research Program of the National Institutes of Health, National Library of Medicine. H. A. is a graduated member of the international MD-PhD program at Hannover Medical School. NR 39 TC 95 Z9 98 U1 1 U2 8 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 APR 12 PY 2012 VL 119 IS 15 BP 3450 EP 3457 DI 10.1182/blood-2011-09-378158 PG 8 WC Hematology SC Hematology GA 927OK UT WOS:000302917200017 PM 22294732 ER PT J AU Walz, C Ahmed, W Lazarides, K Betancur, M Patel, N Hennighausen, L Zaleskas, VM Van Etten, RA AF Walz, Christoph Ahmed, Wesam Lazarides, Katherine Betancur, Monica Patel, Nihal Hennighausen, Lothar Zaleskas, Virginia M. Van Etten, Richard A. TI Essential role for Stat5a/b in myeloproliferative neoplasms induced by BCR-ABL1 and JAK2(V617F) in mice SO BLOOD LA English DT Article ID CHRONIC MYELOID-LEUKEMIA; DNA-BINDING ACTIVITY; BONE-MARROW; BCR-ABL; LYMPHOBLASTIC-LEUKEMIA; INDUCED TRANSFORMATION; LYMPHOID DEVELOPMENT; EFFICIENT INDUCTION; GENE-EXPRESSION; STEM-CELLS AB STAT5 proteins are constitutively activated in malignant cells from many patients with leukemia, including the myeloproliferative neoplasms (MPNs) chronic myeloid leukemia (CML) and polycythemia vera (PV), but whether STAT5 is essential for the pathogenesis of these diseases is not known. In the present study, we used mice with a conditional null mutation in the Stat5a/b gene locus to determine the requirement for STAT5 in MPNs induced by BCR-ABL1 and JAK2(V617F) in retroviral transplantation models of CML and PV. Loss of one Stat5a/b allele resulted in a decrease in BCR-ABL1-induced CML-like MPN and the appearance of B-cell acute lymphoblastic leukemia, whereas complete deletion of Stat5a/b prevented the development of leukemia in primary recipients. However, BCR-ABL1 was expressed and active in Stat5-null leukemic stem cells, and Stat5 deletion did not prevent progression to lymphoid blast crisis or abolish established B-cell acute lymphoblastic leukemia. JAK2(V617F) failed to induce polycythemia in recipients after deletion of Stat5a/b, although the loss of STAT5 did not prevent the development of myelofibrosis. These results demonstrate that STAT5a/b is essential for the induction of CML-like leukemia by BCR-ABL1 and of polycythemia by JAK2(V617F), and validate STAT5a/b and the genes they regulate as targets for therapy in these MPNs. (Blood. 2012;119(15):3550-3560) C1 [Walz, Christoph; Ahmed, Wesam; Lazarides, Katherine; Betancur, Monica; Patel, Nihal; Zaleskas, Virginia M.; Van Etten, Richard A.] Tufts Med Ctr, Mol Oncol Res Inst, Boston, MA 02111 USA. [Ahmed, Wesam; Zaleskas, Virginia M.; Van Etten, Richard A.] Tufts Med Ctr, Div Hematol Oncol, Boston, MA 02111 USA. [Hennighausen, Lothar] NIDDK, Lab Genet & Physiol, NIH, Bethesda, MD USA. RP Van Etten, RA (reprint author), Tufts Med Ctr, Mol Oncol Res Inst, 800 Washington St,Box 5609, Boston, MA 02111 USA. EM rvanetten@tuftsmedicalcenter.org FU National Institutes of Health [CA090576, HL089747, T32 CA09429]; German Research Foundation Deutsche Forschungsgemeinschaft FX This work was supported by the National Institutes of Health (grants CA090576 and HL089747 to R. A. V. and grant T32 CA09429 to W.A.) and the German Research Foundation Deutsche Forschungsgemeinschaft (to C.W.). NR 47 TC 62 Z9 65 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 APR 12 PY 2012 VL 119 IS 15 BP 3550 EP 3560 DI 10.1182/blood-2011-12-397554 PG 11 WC Hematology SC Hematology GA 927OK UT WOS:000302917200027 PM 22234689 ER PT J AU Sheng, JS Wu, LG AF Sheng, Jiansong Wu, Ling-Gang TI Cysteine String Protein alpha: A New Role in Vesicle Recycling SO NEURON LA English DT Editorial Material ID CSP-ALPHA; ENDOCYTOSIS; MECHANISMS; SNAP-25; SYNAPSE AB Zhang et al. (2012) and Rozas et al. (2012) in this issue of Neuron find that cysteine string protein a, a protein involved in neurodegeneration, regulates vesicle endocytosis via interaction with dynamin 1, which may participate in regulating synaptic transmission and possibly in maintaining synapses. C1 [Sheng, Jiansong; Wu, Ling-Gang] Natl Inst Neurol Disorders & Stroke, Synapt Transmiss Sect, Bethesda, MD 20892 USA. RP Wu, LG (reprint author), Natl Inst Neurol Disorders & Stroke, Synapt Transmiss Sect, 35 Convent Dr,Bldg 35,Rm 2B-1012, Bethesda, MD 20892 USA. EM wul@ninds.nih.gov RI SHENG, JIANSONG/K-1914-2013 FU Intramural NIH HHS [ZIA NS003009-08] NR 15 TC 2 Z9 2 U1 1 U2 4 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 0896-6273 EI 1097-4199 J9 NEURON JI Neuron PD APR 12 PY 2012 VL 74 IS 1 BP 6 EP 8 DI 10.1016/j.neuron.2012.03.013 PG 3 WC Neurosciences SC Neurosciences & Neurology GA 927FZ UT WOS:000302893800003 PM 22500624 ER PT J AU Dong, ZQ Yang, N Yeo, SY Chitnis, A Guo, S AF Dong, Zhiqiang Yang, Nan Yeo, Sang-Yeob Chitnis, Ajay Guo, Su TI Intralineage Directional Notch Signaling Regulates Self-Renewal and Differentiation of Asymmetrically Dividing Radial Glia SO NEURON LA English DT Article ID NEURAL STEM-CELLS; C-ELEGANS EMBRYOS; NERVOUS-SYSTEM; NEUROEPITHELIAL CELLS; MIND BOMB; INTERMEDIATE PROGENITORS; RETINAL DEVELOPMENT; NUCLEAR MIGRATION; CORTICAL-NEURONS; IN-VIVO AB Asymmetric division of progenitor/stem cells generates both self-renewing and differentiating progeny and is fundamental to development and regeneration. How this process is regulated in the vertebrate brain remains incompletely understood. Here, we use time-lapse imaging to track radial glia progenitor behavior in the developing zebrafish brain. We find that asymmetric division invariably generates a basal self-renewing daughter and an apical differentiating sibling. Gene expression and genetic mosaic analysis further show that the apical daughter is the source of Notch ligand that is essential to maintain higher Notch activity in the basal daughter. Notably, establishment of this intralineage and directional Notch signaling requires the intrinsic polarity regulator Partitioning defective protein-3 (Par-3), which segregates the fate determinant Mind bomb unequally to the apical daughter, thereby restricting the self-renewal potential to the basal daughter. These findings reveal with single-cell resolution how self-renewal and differentiation become precisely segregated within asymmetrically dividing neural progenitor/stem lineages. C1 [Dong, Zhiqiang; Yang, Nan; Guo, Su] Univ Calif San Francisco, Dept Bioengn & Therapeut Sci, Program Human Genet, San Francisco, CA 94143 USA. [Dong, Zhiqiang; Yang, Nan; Guo, Su] Univ Calif San Francisco, Dept Bioengn & Therapeut Sci, Program Biol Sci, San Francisco, CA 94143 USA. [Yeo, Sang-Yeob; Chitnis, Ajay] NICHHD, Sect Neural Dev Dynam, Mol Genet Lab, NIH, Bethesda, MD 20892 USA. RP Guo, S (reprint author), Univ Calif San Francisco, Dept Bioengn & Therapeut Sci, Program Human Genet, San Francisco, CA 94143 USA. EM su.guo@ucsf.edu RI Yang, Nan/H-3174-2012 FU NIH [NS042626] FX We thank Dr. J. Lewis for zebrafish Dla and Did antibodies, Drs. P. Soba and Y.N. Jan for the UAS-TdTomato plasmids, Drs. A. Kriegstein, J. Rubenstein, and S. Wilson and the S.G. lab members for discussions; Dr. B. Lu and S.G. lab members for critically reading the manuscript; Dr. K. Thorn and the UCSF Nikon imaging center for assistance with confocal microscopy; and M. Munchua for fish husbandry. This work was supported by the NIH Grant NS042626. S.G. was a Searle Scholar and a Science and Engineering Fellow of the David and Lucile Packard foundation. NR 74 TC 48 Z9 50 U1 1 U2 16 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 0896-6273 J9 NEURON JI Neuron PD APR 12 PY 2012 VL 74 IS 1 BP 65 EP 78 DI 10.1016/j.neuron.2012.01.031 PG 14 WC Neurosciences SC Neurosciences & Neurology GA 927FZ UT WOS:000302893800010 PM 22500631 ER PT J AU Rai, G Vyjayanti, VN Dorjsuren, D Simeonov, A Jadhav, A Wilson, DM Maloney, DJ AF Rai, Ganesha Vyjayanti, Vaddadi N. Dorjsuren, Dorjbal Simeonov, Anton Jadhav, Ajit Wilson, David M., III Maloney, David J. TI Synthesis, Biological Evaluation, and Structure-Activity Relationships of a Novel Class of Apurinic/Apyrimidinic Endonuclease 1 Inhibitors SO JOURNAL OF MEDICINAL CHEMISTRY LA English DT Article ID BASE EXCISION-REPAIR; HUMAN APURINIC ENDONUCLEASE; SMALL-MOLECULE INHIBITOR; DNA-REPAIR; CANCER CELLS; BREAST-CANCER; MAJOR HUMAN; APE1; PROTEIN; TEMOZOLOMIDE AB APE1 is an essential protein that operates in the base excision repair (BER) pathway and is responsible for >= 95% of the total apurinic/apyrimidinic (AP) endonuclease activity in human cells. BER is a major pathway that copes with DNA damage induced by several anticancer agents, including ionizing radiation and temozolomide. Overexpression of APEI and enhanced AP endonuclease activity have been linked to increased resistance of tumor cells to treatment with monofunctional alkylators, implicating inhibition of APEI as a valid strategy for cancer therapy. We report herein the results of a focused medicinal chemistry effort around a novel APEI inhibitor, N-(3-(benzo[d]thiazol-2-yl)-6-isopropyl-4,5,6,7-tetrahydrothieno[2,3-c]pyridin-2-yl)acetamide (3). Compound 3 and related analogues exhibit single-digit micromolar activity against the purified APE1 enzyme and comparable activity in HeLa whole cell extract assays and potentiate the cytotoxicity of the alkylating agents methylmethane sulfonate and temozolomide. Moreover, this class of compounds possesses a generally favorable in vitro ADME profile, along with good exposure levels in plasma and brain following intraperitoneal dosing (30 mg/kg body weight) in mice. C1 [Rai, Ganesha; Dorjsuren, Dorjbal; Simeonov, Anton; Jadhav, Ajit; Maloney, David J.] Natl Ctr Adv Translat Sci, NIH, Chem Genom Ctr, Bethesda, MD 20892 USA. [Vyjayanti, Vaddadi N.; Wilson, David M., III] NIA, Lab Mol Gerontol, NIH, Baltimore, MD 21224 USA. RP Maloney, DJ (reprint author), Natl Ctr Adv Translat Sci, NIH, Chem Genom Ctr, Bethesda, MD 20892 USA. EM wilsonda@mail.nih.gov; maloneyd@mail.nih.gov FU NIH, National Institute on Aging; NIH [R03 MH086444-01]; Molecular Libraries Initiative of the National Institutes of Health Roadmap for Medical Research FX The authors thank William Leister, Paul Shinn, Danielle Van Leer, James Bougie, and Tom Daniel for assistance with compound management and purification. We also thank Christina Greco for critical reading of the manuscript and technical assistance. This research was supported by the Intramural Research Program of the NIH, National Institute on Aging, as well as by the NIH Grant R03 MH086444-01 (D.M.W.), and the Molecular Libraries Initiative of the National Institutes of Health Roadmap for Medical Research. NR 34 TC 19 Z9 21 U1 0 U2 7 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 APR 12 PY 2012 VL 55 IS 7 BP 3101 EP 3112 DI 10.1021/jm201537d PG 12 WC Chemistry, Medicinal SC Pharmacology & Pharmacy GA 923AT UT WOS:000302591100020 PM 22455312 ER PT J AU Rodrigues, J Oliveira, GA Kotsyfakis, M Dixit, R Molina-Cruz, A Jochim, R Barillas-Mury, C AF Rodrigues, Janneth Oliveira, Giselle A. Kotsyfakis, Michalis Dixit, Rajnikant Molina-Cruz, Alvaro Jochim, Ryan Barillas-Mury, Carolina TI An Epithelial Serine Protease, AgESP, Is Required for Plasmodium Invasion in the Mosquito Anopheles gambiae SO PLOS ONE LA English DT Article ID TIME BOMB MODEL; OOKINETE INVASION; MIDGUT CELLS; MALARIA PARASITES; SALIVARY-GLANDS; REAL-TIME; FALCIPARUM; STEPHENSI; VECTOR; SPOROZOITES AB Background: Plasmodium parasites need to cross the midgut and salivary gland epithelia to complete their life cycle in the mosquito. However, our understanding of the molecular mechanism and the mosquito genes that participate in this process is still very limited. Methodology/Principal Findings: We identified an Anopheles gambiae epithelial serine protease (AgESP) that is constitutively expressed in the submicrovillar region of mosquito midgut epithelial cells and in the basal side of the salivary glands that is critical for Plasmodium parasites to cross these two epithelial barriers. AgESP silencing greatly reduces Plasmodium berghei and Plasmodium falciparum midgut invasion and prevents the transcriptional activation of gelsolin, a key regulator of actin remodeling and a reported Plasmodium agonist. AgESP expression is highly induced in midgut cells invaded by Plasmodium, suggesting that this protease also participates in the apoptotic response to invasion. In salivary gland epithelial cells, AgESP is localized on the basal side-the surface with which sporozoites interact. AgESP expression in the salivary gland is also induced in response to P. berghei and P. falciparum sporozoite invasion, and AgESP silencing significantly reduces the number of sporozoites that invade this organ. Conclusion: Our findings indicate that AgESP is required for Plasmodium parasites to effectively traverse the midgut and salivary gland epithelial barriers. Plasmodium parasites need to modify the actin cytoskeleton of mosquito epithelial cells to successfully complete their life cycle in the mosquito and AgESP appears to be a major player in the regulation of this process. C1 [Rodrigues, Janneth; Oliveira, Giselle A.; Kotsyfakis, Michalis; Dixit, Rajnikant; Molina-Cruz, Alvaro; Jochim, Ryan; Barillas-Mury, Carolina] NIAID, Lab Malaria & Vector Res, NIH, Rockville, MD USA. RP Rodrigues, J (reprint author), Univ Washington, Dept Chem, Seattle, WA 98195 USA. EM cbarillas@niaid.nih.gov RI Jochim, Ryan/C-6756-2013; Kotsyfakis, Michail/G-9525-2014; OI Kotsyfakis, Michail/0000-0002-7526-1876; Oliveira, Giselle/0000-0002-5898-7843; DIXIT, RAJNIKANT/0000-0002-3536-8329 FU Division of Intramural Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health FX This work was supported by the Intramural Research Program of the Division of Intramural Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 29 TC 10 Z9 10 U1 0 U2 7 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA SN 1932-6203 J9 PLOS ONE JI PLoS One PD APR 11 PY 2012 VL 7 IS 4 AR e35210 DI 10.1371/journal.pone.0035210 PG 8 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 959TP UT WOS:000305336600093 PM 22509400 ER PT J AU Xiong, W Wu, XW Lovinger, DM Zhang, L AF Xiong, Wei Wu, Xiongwu Lovinger, David M. Zhang, Li TI A Common Molecular Basis for Exogenous and Endogenous Cannabinoid Potentiation of Glycine Receptors SO JOURNAL OF NEUROSCIENCE LA English DT Article ID SUBUNIT-SPECIFIC MODULATION; SWISS-MODEL; ALLOSTERIC MODULATION; MEDIATED RESPONSES; 5-HT3A RECEPTORS; XENOPUS OOCYTES; KNOCKOUT MICE; SR 141716A; ANANDAMIDE; LIGANDS AB Both exogenous and endogenous cannabinoids can allosterically modulate glycine receptors (GlyRs). However, little is known about the molecular basis of cannabinoid-GlyR interactions. Here we report that sustained incubation with the endocannabinoid anandamide (AEA) substantially increased the amplitude of glycine-activated current in both rat cultured spinal neurons and in HEK-293 cells expressing human alpha 1, rat alpha 2 and alpha 3 GlyRs. While the alpha 1 and alpha 3 subunits were highly sensitive to AEA-induced potentiation, the alpha 2 subunit was relatively insensitive to AEA. Switching a serine at 296 and 307 in the TM3 (transmembrane domain 3) of the alpha 1 and alpha 3 subunits with an alanine (A) at the equivalent position in the alpha 2 subunit converted the alpha 1/alpha 3 AEA-sensitive receptors to sensitivity resembling that of alpha 2. The S296 residue is also critical for exogenous cannabinoid-induced potentiation of I-Gly. The magnitude of AEA potentiation decreased with removal of either the hydroxyl or oxygen groups on AEA. While desoxy-AEA was significantly less efficacious in potentiating I-Gly, desoxy-AEA inhibited potentiation produced by both Delta(9)-tetrahydrocannabinol (THC), a major psychoactive component of marijuana, and AEA. Similarly, didesoxy-THC, a modified THC with removal of both hydroxyl/oxygen groups, did not affect I-Gly when applied alone but inhibited the potentiation of I-Gly induced by AEA and THC. These findings suggest that exogenous and endogenous cannabinoids potentiate GlyRs via a hydrogen bonding-like interaction. Such a specific interaction likely stems from a common molecular basis involving the S296 residue in the TM3 of the alpha 1 and alpha 3 subunits. C1 [Xiong, Wei; Lovinger, David M.; Zhang, Li] NIAAA, Lab Integrat Neurosci, NIH, Bethesda, MD 20892 USA. [Wu, Xiongwu] NHLBI, Lab Computat Biol, NIH, Bethesda, MD 20892 USA. RP Zhang, L (reprint author), NIAAA, Lab Integrat Neurosci, NIH, 5625 Fishers Lane, Bethesda, MD 20892 USA. EM lzhang@mail.nih.gov FU National Institute on Alcohol Abuse and Alcoholism FX This work was supported by funds from the intramural program of the National Institute on Alcohol Abuse and Alcoholism. We thank Drs. Kejun Cheng and Fuying Li for providing modified cannabinoids (didesoxy-THC, desoxy-AEA, and dehydroxyl-AEA). We also thank Dr. Zhifeng Zhou for technical assistance with DNA sequencing. NR 50 TC 14 Z9 15 U1 0 U2 5 PU SOC NEUROSCIENCE PI WASHINGTON PA 11 DUPONT CIRCLE, NW, STE 500, WASHINGTON, DC 20036 USA SN 0270-6474 J9 J NEUROSCI JI J. Neurosci. PD APR 11 PY 2012 VL 32 IS 15 BP 5200 EP 5208 DI 10.1523/JNEUROSCI.6347-11.2012 PG 9 WC Neurosciences SC Neurosciences & Neurology GA 925WT UT WOS:000302793500018 PM 22496565 ER PT J AU Tao, R Li, C Newburn, EN Ye, TZ Lipska, BK Herman, MM Weinberger, DR Kleinman, JE Hyde, TM AF Tao, Ran Li, Chao Newburn, Erin N. Ye, Tianzhang Lipska, Barbara K. Herman, Mary M. Weinberger, Daniel R. Kleinman, Joel E. Hyde, Thomas M. TI Transcript-Specific Associations of SLC12A5 (KCC2) in Human Prefrontal Cortex with Development, Schizophrenia, and Affective Disorders SO JOURNAL OF NEUROSCIENCE LA English DT Article ID GLUTAMIC-ACID DECARBOXYLASE; CATION-CHLORIDE COTRANSPORTERS; BIPOLAR DISORDER; GENE-EXPRESSION; GABA; NEURONS; GAD1; PATHOPHYSIOLOGY; GAD(67); REELIN AB The neuron-specific K+-Cl- cotransporter SLC12A5, also known as KCC2, helps mediate the electrophysiological effects of GABA. The pattern of KCC2 expression during early brain development suggests that its upregulation drives the postsynaptic switch of GABA from excitation to inhibition. We previously found decreased expression of full-length KCC2 in the postmortem hippocampus of patients with schizophrenia, but not in the dorsolateral prefrontal cortex (DLPFC). Using PCR and rapid amplification of cDNA ends, we discovered several previously unrecognized alternative KCC2 transcripts in both human adult and fetal brain in addition to the previously identified full-length (NM_020708.3) and truncated (AK098371) transcripts. We measured the expression levels of four relatively abundant truncated splice variants, including three novel transcripts (Delta EXON6, EXON2B, and EXON6B) and one previously described transcript (AK098371), in a large human cohort of nonpsychiatric controls across the lifespan, and in patients with schizophrenia and affective disorders. In SH-SY5Y cell lines, these transcripts were translated into proteins and expressed at their predicted sizes. Expression of the EXON6B transcript is increased in the DLPFC of patients with schizophrenia (p = 0.03) but decreased in patients with major depression (p = 0.04). The expression of AK098371 is associated with a GAD1 single nucleotide polymorphism (rs3749034) that previously has been associated with GAD67 expression and risk for schizophrenia. Our data confirm the developmental regulation of KCC2 expression, and provide evidence that KCC2 transcripts are differentially expressed in schizophrenia and affective disorders. Alternate transcripts from KCC2 may participate in the abnormal GABA signaling in the DLPFC associated with schizophrenia. C1 [Tao, Ran; Li, Chao; Newburn, Erin N.; Ye, Tianzhang; Lipska, Barbara K.; Herman, Mary M.; Weinberger, Daniel R.; Kleinman, Joel E.; Hyde, Thomas M.] NIMH, Clin Brain Disorders Branch, Genes Cognit & Psychosis Program, Intramural Res Program,NIH, Bethesda, MD 20892 USA. [Ye, Tianzhang; Weinberger, Daniel R.; Hyde, Thomas M.] Johns Hopkins Univ, Med Ctr, Lieber Inst Brain Dev, Baltimore, MD 21205 USA. RP Hyde, TM (reprint author), NIMH, Clin Brain Disorders Branch, Genes Cognit & Psychosis Program, Intramural Res Program,NIH, 10 Ctr Dr,Room 4N312, Bethesda, MD 20892 USA. EM hydet@mail.nih.gov RI Tao, Ran/C-2662-2013; Tao, Ran/L-3460-2014 FU National Institute of Mental Health (NIMH), National Institutes of Health FX This research was supported by the Intramural Research Program of the National Institute of Mental Health (NIMH), National Institutes of Health. We thank Amy Deep-Soboslay, M.Ed., and Llewellyn B. Bigelow, M D., of the Clinical Brain Disorders Branch, Genes, Cognition and Psychosis Program, Intramural Research Program, and NIMH for their efforts in clinical diagnosis and demographic characterization, and Vesna Imamovic, Yeva Snitkovsky, Jewell King, Jonathan Sirovatka, and Liqin Wang, M.D., for their excellent technical assistance. Special gratitude also is extended to H. Ronald Zielke, Ph.D., Robert D. Vigorito, M.S., P.A., and Robert M. Johnson, B.S., of the National Institute of Child Health and Human Development Brain and Tissue Bank for Developmental Disorders at the University of Maryland for their provision of fetal, child, and adolescent brain specimens for this study. NR 40 TC 28 Z9 29 U1 1 U2 6 PU SOC NEUROSCIENCE PI WASHINGTON PA 11 DUPONT CIRCLE, NW, STE 500, WASHINGTON, DC 20036 USA SN 0270-6474 J9 J NEUROSCI JI J. Neurosci. PD APR 11 PY 2012 VL 32 IS 15 BP 5216 EP 5222 DI 10.1523/JNEUROSCI.4626-11.2012 PG 7 WC Neurosciences SC Neurosciences & Neurology GA 925WT UT WOS:000302793500020 PM 22496567 ER PT J AU Colegate, SM Gardner, DR Joy, RJ Betz, JM Panter, KE AF Colegate, Steven M. Gardner, Dale R. Joy, Robert J. Betz, Joseph M. Panter, Kip E. TI Dehydropyrrolizidine Alkaloids, Including Monoesters with an Unusual Esterifying Acid, from Cultivated Crotalaria juncea (Sunn Hemp cv.'Tropic Sun') SO JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY LA English DT Article DE Crotalaria juncea; 'Tropic Sun'; pyrrolizidine alkaloids; N-oxides; HPLC-ESI/MS; junceine; trichodesmine; isohemijunceine; hemijunceine ID TOXIC RANGE PLANTS; PYRROLIZIDINE ALKALOIDS; N-OXIDES; SENECIO; MS; SPECTROSCOPY; CHEMISTRY AB Cultivation of Crotalaria juncea L. (Sunn Hemp cv. 'Tropic Sun') is recommended as a green manure crop in a rotation cycle to improve soil condition, help control erosion, suppress weeds, and reduce soil nematodes. Because C. juncea belongs to a genus that is known for the production of toxic dehydropyrrolizidine alkaloids, extracts of the roots, stems, leaves, and seeds of 'Tropic Sun' were analyzed for their presence using HPLC-ESI/MS. Qualitative analysis identified previously unknown alkaloids as major components along with the expected macrocyclic dehydropyrrolizidine alkaloid diesters, junceine and trichodesmine. The dehydropyrrolizidine alkaloids occurred mainly as the N-oxides in the roots, stems, and, to a lesser extent, leaves, but mainly as the free bases in the seeds. Comprehensive spectrometric and spectroscopic analysis enabled elucidation of the unknown alkaloids as diastereoisomers of isohemijunceine, a monoester of retronecine with an unusual necic acid. The dehydropyrrolizidine alkaloid contents of the roots, stems, and leaves of immature plants were estimated to be 0.05, 0.12, and 0.01% w/w, respectively, whereas seeds were estimated to contain 0.15% w/w. C1 [Colegate, Steven M.; Gardner, Dale R.; Panter, Kip E.] ARS, Poisonous Plant Res Lab, USDA, Logan, UT 84341 USA. [Joy, Robert J.] USDA, Nat Resources Conservat Serv, Plant Mat Ctr, Hoolehua, HI 96729 USA. [Betz, Joseph M.] NIH, Off Dietary Supplements, Bethesda, MD 20892 USA. RP Colegate, SM (reprint author), ARS, Poisonous Plant Res Lab, USDA, 1150 E 1400 N, Logan, UT 84341 USA. EM steven.colegate@ars.usda.gov FU Agricultural Research Service of the U.S. Department of Agriculture; Office of Dietary Supplements of the National Institutes of Health FX This research is supported by the Agricultural Research Service of the U.S. Department of Agriculture and an Interagency Agreement with the Office of Dietary Supplements of the National Institutes of Health. NR 30 TC 18 Z9 18 U1 0 U2 21 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 APR 11 PY 2012 VL 60 IS 14 BP 3541 EP 3550 DI 10.1021/jf205296s PG 10 WC Agriculture, Multidisciplinary; Chemistry, Applied; Food Science & Technology SC Agriculture; Chemistry; Food Science & Technology GA 922CS UT WOS:000302525000001 PM 22429238 ER PT J AU Sinthuvanich, C Veiga, AS Gupta, K Gaspar, D Blumenthal, R Schneider, JP AF Sinthuvanich, Chomdao Veiga, Ana Salome Gupta, Kshitij Gaspar, Diana Blumenthal, Robert Schneider, Joel P. TI Anticancer beta-Hairpin Peptides: Membrane-Induced Folding Triggers Activity SO JOURNAL OF THE AMERICAN CHEMICAL SOCIETY LA English DT Article ID TUMOR BLOOD-VESSELS; ANTIMICROBIAL PEPTIDE; PLASMA-MEMBRANE; AMINOPHOSPHOLIPID TRANSLOCASE; ANIONIC PHOSPHOLIPIDS; CANCER-TREATMENT; LYTIC PEPTIDES; CELLS; PHOSPHATIDYLSERINE; CONFORMATION AB Several cationic antimicrobial peptides (AMPs) have recently been shown to display anticancer activity via a mechanism that usually entails the disruption of cancer cell membranes. In this work, we designed an 18-residue anticancer peptide, SVS-1, whose mechanism of action is designed to take advantage of the aberrant lipid composition presented on the outer leaflet of cancer cell membranes, which makes the surface of these cells electronegative relative to the surface of noncancerous cells. SVS-1 is designed to remain unfolded and inactive in aqueous solution but to preferentially fold at the surface of cancer cells, adopting an amphiphilic beta-hairpin structure capable of membrane disruption. Membrane-induced folding is driven by electrostatic interaction between the peptide and the negatively charged membrane surface of cancer cells. SVS-1 is active against a variety of cancer cell lines such as A549 (lung carcinoma), KB (epidermal carcinoma), MCF-7 (breast carcinoma), and MDA-MB-436 (breast carcinoma). However, the cytotoxicity toward noncancerous cells having typical membrane compositions, such as HUVEC and erythrocytes, is low. CD spectroscopy, appropriately designed peptide controls, cell-based studies, liposome leakage assays, and electron microscopy support the intended mechanism of action, which leads to preferential killing of cancerous cells. C1 [Sinthuvanich, Chomdao; Veiga, Ana Salome; Schneider, Joel P.] NCI, Biol Chem Lab, Frederick, MD 21702 USA. [Sinthuvanich, Chomdao] Univ Delaware, Dept Chem & Biochem, Newark, DE 19716 USA. [Veiga, Ana Salome; Gaspar, Diana] Univ Lisbon, Inst Mol Med, Fac Med, P-1649028 Lisbon, Portugal. [Gupta, Kshitij; Blumenthal, Robert] NCI, Membrane Struct & Funct Sect, Nanobiol Program, Frederick, MD 21702 USA. RP Schneider, JP (reprint author), NCI, Biol Chem Lab, Frederick, MD 21702 USA. EM Joel.Schneider@nih.gov RI Schneider, Joel/N-2610-2014; Gaspar, Diana/M-9562-2015 OI Gaspar, Diana/0000-0002-9602-567X FU Strategic Scholarship for Frontier Research Network (SFR) from the Office of the Higher Education Commission, Ministry of Education, Thailand; European Community [PIOE-GA-2009-235154]; Fundacao para a Ciencia e a Tecnologia (Ministerio da Educacao e Ciencia, Portugal) [SFRH/BPD/73500/2010]; National Cancer Institute, National Institutes of Health FX We thank Adam Harned, Christina Burks, and Ulrich Baxa from the Electron Microscopy Laboratory (SAIC-Frederick) for electron microscopy images and Marco Domingues for assistance with preliminary leakage experiments. This work was partially supported by a graduate fellowship awarded to C.S. through the Strategic Scholarship for Frontier Research Network (SFR) from the Office of the Higher Education Commission, Ministry of Education, Thailand. A Marie Curie International Outgoing Fellowship within the 7th European Community Framework Programme partilly supported A.S.V. (PIOE-GA-2009-235154). D.G. acknowledges Fundacao para a Ciencia e a Tecnologia (Ministerio da Educacao e Ciencia, Portugal) for Fellowship SFRH/BPD/73500/2010. Research funding was provided by the Intramural Research Program of the National Cancer Institute, National Institutes of Health. NR 38 TC 55 Z9 56 U1 6 U2 49 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 APR 11 PY 2012 VL 134 IS 14 BP 6210 EP 6217 DI 10.1021/ja210569f PG 8 WC Chemistry, Multidisciplinary SC Chemistry GA 922CQ UT WOS:000302524800030 PM 22413859 ER PT J AU Zhang, YL Muthana, SM Farnsworth, D Ludek, O Adams, K Barchi, JJ Gildersleeve, JC AF Zhang, Yalong Muthana, Saddam M. Farnsworth, David Ludek, Olaf Adams, Kristie Barchi, Joseph J., Jr. Gildersleeve, Jeffrey C. TI Enhanced Epimerization of Glycosylated Amino Acids During Solid-Phase Peptide Synthesis SO JOURNAL OF THE AMERICAN CHEMICAL SOCIETY LA English DT Article ID TOTAL CHEMICAL-SYNTHESIS; ANTIPROLIFERATIVE FACTOR; GLYCOPEPTIDE SYNTHESIS; POSTTRANSLATIONAL MODIFICATION; GLYCAN MICROARRAYS; CLINICAL-TRIALS; O-GLYCOPEPTIDE; TN-ANTIGEN; CANCER; ANTIBODIES AB Glycopeptides are extremely useful for basic research and clinical applications, but access to structurally defined glycopeptides is limited by the difficulties in synthesizing this class of compounds. In this study, we demonstrate that many common peptide coupling conditions used to prepare O-linked glycopeptides result in substantial amounts of epimerization at the a position. In fact, epimerization resulted in up to 80% of the non-natural epimer, indicating that it can be the major product in some reactions. Through a series of mechanistic studies, we demonstrate that the enhanced epimerization relative to nonglycosylated amino acids is due to a combination of factors, including a faster rate of epimerization, an energetic preference for the unnatural epimer over the natural epimer, and a slower overall rate of peptide coupling. In addition, we demonstrate that use of 2,4,6-trimethylpyridine (TMP) as the base in peptide couplings produces glycopeptides with high efficiency and low epimerization. The information and improved reaction conditions will facilitate the preparation of glycopeptides as therapeutic compounds and vaccine antigens. C1 [Zhang, Yalong; Muthana, Saddam M.; Farnsworth, David; Ludek, Olaf; Adams, Kristie; Barchi, Joseph J., Jr.; Gildersleeve, Jeffrey C.] NCI, Biol Chem Lab, Frederick, MD 21702 USA. RP Gildersleeve, JC (reprint author), NCI, Biol Chem Lab, 376 Boyles St,Bldg 376, Frederick, MD 21702 USA. EM gildersj@mail.nih.gov RI Gildersleeve, Jeffrey/N-3392-2014; Barchi Jr., Joseph/N-3784-2014 FU NIH, NCI FX This research was supported by the Intramural Research Program of the NIH, NCI. We gratefully acknowledge James A. Kelley (NIH/NCI) for obtaining mass spectrometry data for all the compounds. NR 66 TC 25 Z9 25 U1 3 U2 28 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 APR 11 PY 2012 VL 134 IS 14 BP 6316 EP 6325 DI 10.1021/ja212188r PG 10 WC Chemistry, Multidisciplinary SC Chemistry GA 922CQ UT WOS:000302524800041 PM 22390544 ER PT J AU Eddy, MT Ong, TC Clark, L Teijido, O van der Wel, PCA Garces, R Wagner, G Rostovtseva, TK Griffin, RG AF Eddy, Matthew T. Ong, Ta-Chung Clark, Lindsay Teijido, Oscar van der Wel, Patrick C. A. Garces, Robert Wagner, Gerhard Rostovtseva, Tatiana K. Griffin, Robert G. TI Lipid Dynamics and Protein-Lipid Interactions in 2D Crystals Formed with the beta-Barrel Integral Membrane Protein VDAC1 SO JOURNAL OF THE AMERICAN CHEMICAL SOCIETY LA English DT Article ID NUCLEAR-MAGNETIC-RESONANCE; SOLID-STATE NMR; OUTER MITOCHONDRIAL-MEMBRANE; ANION-SELECTIVE CHANNEL; ANGLE-SPINNING NMR; 2-DIMENSIONAL CRYSTALS; NEUROSPORA-CRASSA; CELL-MEMBRANES; SCHIFF-BASE; H-2 NMR AB We employ a combination of C-13/N-15 magic angle spinning (MAS) NMR and H-2 NMR to study the structural and functional consequences of different membrane environments on VDAC1 and, conversely, the effect of VDAC1 on the structure of the lipid bilayer. MAS spectra reveal a well-structured VDAC1 in 2D crystals of dimyristoylphosphatidylcholine (DMPC) and diphytanoylphosphatidylcholine (DPhPC,), and their temperature dependence suggests that the VDAC structure does not change conformation above and below the lipid phase transition temperature. The same data show that the N-terminus remains structured at both low and high temperatures. Importantly, functional studies based on electrophysiological measurements on these same samples show fully functional channels, even without the presence of Triton X-100 that has been found necessary for in vitro-refolded channels. H-2 solid-state NMR and differential scanning calorimetry were used to investigate the dynamics and phase behavior of the lipids within the VDAC1 2D crystals. H-2 NMR spectra indicate that the presence of protein in DMPC results in a broad lipid phase transition that is shifted from 19 to similar to 27 degrees C and show the existence of different lipid populations, consistent with the presence of both annular and bulk lipids in the functionally and structurally homogeneous samples. C1 [Eddy, Matthew T.; Ong, Ta-Chung; Clark, Lindsay; van der Wel, Patrick C. A.; Griffin, Robert G.] MIT, Dept Chem, Cambridge, MA 02139 USA. [Eddy, Matthew T.; Ong, Ta-Chung; Clark, Lindsay; van der Wel, Patrick C. A.; Griffin, Robert G.] MIT, Francis Bitter Magnet Lab, Cambridge, MA 02139 USA. [Teijido, Oscar; Rostovtseva, Tatiana K.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Program Phys Biol, NIH, Bethesda, MD 20892 USA. [Garces, Robert; Wagner, Gerhard] Harvard Univ, Sch Med, Dept Biol & Mol Pharmacol, Boston, MA 02115 USA. RP Griffin, RG (reprint author), MIT, Dept Chem, Cambridge, MA 02139 USA. EM rgg@mit.edu RI van der Wel, Patrick/B-1428-2009 OI van der Wel, Patrick/0000-0002-5390-3321 FU NIH [EB001960, EB002026, GM075879]; Eunice Kennedy Shriver National Institute of Child Health and Human Development, NIH FX We wish to thank Nicki Watson from the Whitehead Institute and Maria Ericsson from Harvard Medical School for acquiring EM images and Dr. David Ruben for help with de-Pake-ing. The Biophysical Instrumentation Facility for the Study of Complex Macromolecular Systems (NSF-0070319 and NIH GM68762) is gratefully acknowledged for help acquiring the DSC data. This research was supported by NIH grants EB001960, EB002026, and GM075879. O.T. and T.K.R. wish to thank Sergey Bezrukov for fruitful discussions and Kely Sheldon for help with experiments and acknowledge support by the Intramural Research Program of the Eunice Kennedy Shriver National Institute of Child Health and Human Development, NIH. NR 109 TC 30 Z9 30 U1 3 U2 29 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 APR 11 PY 2012 VL 134 IS 14 BP 6375 EP 6387 DI 10.1021/ja300347v PG 13 WC Chemistry, Multidisciplinary SC Chemistry GA 922CQ UT WOS:000302524800047 PM 22435461 ER PT J AU Milman, G Schwope, DM Gorelick, DA Huestis, MA AF Milman, Garry Schwope, David M. Gorelick, David A. Huestis, Marilyn A. TI Cannabinoids and metabolites in expectorated oral fluid following controlled smoked cannabis SO CLINICA CHIMICA ACTA LA English DT Article DE Oral fluid; Expectoration; Cannabinoids; Delta 9-Tetrahydrocannabinol; Detection window; Cannabis ID MARIJUANA SMOKING; DELTA(9)-TETRAHYDROCANNABINOL; DRUGS; DELTA-9-TETRAHYDROCANNABINOL; DISPOSITION; COLLECTION; SPECIMENS; SALIVA; ABUSE; HAIR AB Background: Delta(9)-Tetrahydrocannabinol (THC) in oral fluid (OF) implies cannabis intake, but eliminating passive exposure and improving interpretation of test results requires additional research. Methods: Ten adult cannabis users smoked ad libitum one 6.8% THC cigarette. Expectorated OF was collected for up to 22 h, and analyzed within 24 h of collection. THC, 11-nor-9-carboxy-THC (THCCOOH), cannabidiol, and cannabinol were quantified by 2-dimensional-GCMS. Results: Eighty specimens were analyzed: 6 could not be collected due to dry mouth. THC was quantifiable in 95.2%, cannabidiol in 69.3%, cannabinol in 62.3%, and THCCOOH in 94.7% of specimens. Highest THC, cannabidiol, and cannabinol concentrations were 22370, 1000, and 1964 mu g/l, respectively, 0.25 h after the start of smoking; THCCOOH peaked within 2 h (up to 560 ng/l). Concentrations 6 h after smoking were THC (0.9-90.4 mu g/l) and THCCOOH (17.0-151 ng/l) (8 of 9 positive for both); only 4 were positive for cannabidiol (0.5-2.4 mu g/l) and cannabinol (1.0-3.0 mu g/l). By 22 h, there were 4 THC (0.4-10.3 mu g/l), 5 THCCOOH (6.0-24.0 ng/l), 1 cannabidiol (0.3 mu g/l), and no cannabinol positive specimens. Conclusions: THCCOOH in OF suggests no passive contamination, and CBD and CBN suggest recent cannabis smoking. Seventeen alternative cutoffs were evaluated to meet the needs of different drug testing programs. Published by Elsevier B.V. C1 [Huestis, Marilyn A.] Natl Inst Drug Abuse, IRP, NIH, Biomed Res Ctr, Baltimore, MD 21224 USA. RP Huestis, MA (reprint author), Natl Inst Drug Abuse, IRP, NIH, Biomed Res Ctr, 251 Bayview Blvd,Room 05A-721, Baltimore, MD 21224 USA. EM mhuestis@intra.nida.nih.gov FU National Institute on Drug Abuse, National Institutes of Health FX We acknowledge the contributions of the clinical staff of the National Institute on Drug Abuse, Intramural Research Program and the Behavioral Research Pharmacology Unit. Funding was provided by the Intramural Research Program, National Institute on Drug Abuse, National Institutes of Health. NR 28 TC 27 Z9 28 U1 4 U2 17 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0009-8981 J9 CLIN CHIM ACTA JI Clin. Chim. Acta PD APR 11 PY 2012 VL 413 IS 7-8 BP 765 EP 770 DI 10.1016/j.cca.2012.01.011 PG 6 WC Medical Laboratory Technology SC Medical Laboratory Technology GA 913WL UT WOS:000301908000021 PM 22285315 ER PT J AU Farkas, S Nagy, K Jia, ZS Harkany, T Palkovits, M Donohou, SR Pike, VW Halldin, C Mathe, D Csiba, L Gulyas, B AF Farkas, Szabolcs Nagy, Katalin Jia, Zhisheng Harkany, Tibor Palkovits, Miklos Donohou, Sean R. Pike, Victor W. Halldin, Christer Mathe, Domokos Csiba, Laszlo Gulyas, Balazs TI The decrease of dopamine D-2/D-3 receptor densities in the putamen and nucleus caudatus goes parallel with maintained levels of CB1 cannabinoid receptors in Parkinson's disease: A preliminary autoradiographic study with the selective dopamine D-2/D-3 antagonist [H-3]raclopride and the novel CB1 inverse agonist [I-125]SD7015 SO BRAIN RESEARCH BULLETIN LA English DT Article DE Parkinson's disease; Endocannabinoid CB1 receptor; Dopamine D-2/D-3 receptor; Molecular imaging biomarker; Human brain autoradiography; Striatum ID MESSENGER-RNA EXPRESSION; RAT BASAL GANGLIA; ENDOCANNABINOID SYSTEM; HUMAN BRAIN; IN-VIVO; HUNTINGTONS-DISEASE; D2 RECEPTORS; ENDOGENOUS CANNABINOIDS; DENERVATED STRIATUM; SUBSTANTIA-NIGRA AB Cannabinoid type-1 receptors (CB1 Rs) modulate synaptic neurotransmission by participating in retrograde signaling in the adult brain. Increasing evidence suggests that cannabinoids through CB1 Rs play an important role in the regulation of motor activities in the striatum. In the present study, we used human brain samples to examine the relationship between CB1 R and dopamine receptor density in case of Parkinson's disease (PD). Post mortem putamen, nucleus caudatus and medial frontal gyrus samples obtained from PD patients were used for CB1 R and dopamine D-2/D-3 receptor autoradiography. [I-125]SD7015, a novel selective CB1 R inverse agonist, developed by a number of the present co-authors, and [H-3]raclopride, a dopamine D-2/D-3 antagonist, were used as radioligands. Our results demonstrate unchanged CB1 R density in the putamen and nucleus caudatus of deceased PD patients, treated with levodopa (L-DOPA). At the same time dopamine D-2/D-3 receptors displayed significantly decreased density levels in case of PD putamen (control: 47.97 +/- 10.00 fmol/g, PD: 3.73 +/- 0.07 fmol/g (mean +/- SEM), p < 0.05) and nucleus caudatus (control: 30.26 +/- 2.48 fmol/g, PD: 12.84 +/- 5.49 fmol/g, p < 0.0005) samples. In contrast to the putamen and the nucleus caudatus, in the medial frontal gyrus neither receptor densities were affected. Our data suggest the presence of an unaltered CB1 R population even in late stages of levodopa treated PD. This further supports the presence of an intact CB1 R population which, in line with the conclusion of earlier publications, may be utilized as a pharmacological target in the treatment of PD. Furthermore we found discrepancy between a maintained CB1 R population and a decreased dopamine D-2/D-3 receptor population in PD striatum. The precise explanation of this conundrum requires further studies with simultaneous examination of the central cannabinoid and dopaminergic systems in PD using higher sample size. (C) 2012 Elsevier Inc. All rights reserved. C1 [Jia, Zhisheng; Halldin, Christer; Gulyas, Balazs] Karolinska Inst, Dept Clin Neurosci, Psychiat Sect, S-17176 Stockholm, Sweden. [Farkas, Szabolcs; Nagy, Katalin] Univ Debrecen, Dept Neurol, H-4012 Debrecen, Hungary. [Harkany, Tibor] Karolinska Inst, Dept Med Biochem & Biophys, Div Mol Neurobiol, S-17177 Stockholm, Sweden. [Palkovits, Miklos] Semmelweis Univ, Dept Anat, H-1094 Budapest, Hungary. [Donohou, Sean R.; Pike, Victor W.] NIMH, Mol Imaging Branch, NIH, Bethesda, MD 20892 USA. [Mathe, Domokos] Semmelweis Univ, Dept Biophys & Radiat Biol, H-1094 Budapest, Hungary. [Mathe, Domokos] CROmed Translat Res Ctr, H-1047 Budapest, Hungary. RP Gulyas, B (reprint author), Karolinska Inst, Dept Clin Neurosci, Psychiat Sect, S-17176 Stockholm, Sweden. EM balazs.gulyas@ki.se RI Palkovits, Miklos/F-2707-2013; Gulyas, Balazs/F-9508-2015 FU Hungarian National Science Found (OTKA) [K 68864] FX The study was supported by the Hungarian National Science Found (OTKA) (K 68864) and was performed partly within a collaborative master research agreement between Karolinska Institutet, Mediso Medical Imaging Systems and CROmed Translational. NR 106 TC 6 Z9 6 U1 0 U2 14 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0361-9230 J9 BRAIN RES BULL JI Brain Res. Bull. PD APR 10 PY 2012 VL 87 IS 6 BP 504 EP 510 DI 10.1016/j.brainresbull.2012.02.012 PG 7 WC Neurosciences SC Neurosciences & Neurology GA 934ZT UT WOS:000303487300002 PM 22421165 ER PT J AU Zhang, XX Eden, HS Chen, XY AF Zhang, Xiao-Xiang Eden, Henry S. Chen, Xiaoyuan TI Peptides in cancer nanomedicine: Drug carriers, targeting ligands and protease substrates SO JOURNAL OF CONTROLLED RELEASE LA English DT Review DE Peptides; Cancer; Nanomedicine; Drug delivery; Tumor targeting; Protease-responsive ID CELL-PENETRATING PEPTIDES; MATRIX METALLOPROTEINASES MMPS; BIOLOGICALLY-ACTIVE PROTEINS; NUCLEIC-ACID DELIVERY; SMALL INTERFERING RNA; TAT-FUSION PROTEINS; VIRUS TYPE-1 VP22; IN-VIVO; MAMMALIAN-CELLS; GENE DELIVERY AB Peptides are attracting increasing attention as therapeutic agents, as the technologies for peptide development and manufacture continue to mature. Concurrently, with booming research in nanotechnology for biomedical applications, peptides have been studied as an important class of components in nanomedicine, and they have been used either alone or in combination with nanomaterials of every reported composition. Peptides possess many advantages, such as smallness, ease of synthesis and modification, and good biocompatibility. Their functions in cancer nanomedicine, discussed in this review, include serving as drug carriers, as targeting ligands, and as protease-responsive substrates for drug delivery. Published by Elsevier B.V. C1 [Chen, Xiaoyuan] NIBIB, LOMIN, NIH, Intramural Res Program, Bethesda, MD 20892 USA. RP Chen, XY (reprint author), NIBIB, LOMIN, NIH, Intramural Res Program, Bldg 31,Room 1C22, Bethesda, MD 20892 USA. EM shawn.chen@nih.gov FU National Institute of Biomedical Imaging and Bioengineering (NIBIB), National Institutes of Health (NIH) FX This work was supported by the intramural research program of the National Institute of Biomedical Imaging and Bioengineering (NIBIB), National Institutes of Health (NIH). This work was performed while X-X Zhang held a National Research Council Research Associateship Award at NIH/NIBIB. NR 190 TC 71 Z9 76 U1 6 U2 106 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0168-3659 J9 J CONTROL RELEASE JI J. Control. Release PD APR 10 PY 2012 VL 159 IS 1 BP 2 EP 13 DI 10.1016/j.jconrel.2011.10.023 PG 12 WC Chemistry, Multidisciplinary; Pharmacology & Pharmacy SC Chemistry; Pharmacology & Pharmacy GA 938LG UT WOS:000303734400002 PM 22056916 ER PT J AU Emens, LA Silverstein, SC Khleif, S Marincola, FM Galon, J AF Emens, Leisha A. Silverstein, Samuel C. Khleif, Samir Marincola, Francesco M. Galon, Jerome TI Toward integrative cancer immunotherapy: targeting the tumor microenvironment SO JOURNAL OF TRANSLATIONAL MEDICINE LA English DT Editorial Material ID ENDOTHELIAL GROWTH-FACTOR; ENHANCES ANTITUMOR IMMUNITY; CELL LUNG-CANCER; T-CELLS; COLORECTAL-CANCER; CLINICAL ACTIVITY; MODULATION; EXPRESSION; CARCINOMA; CHEMOTHERAPY AB The development of cancer has historically been attributed to genomic alterations of normal host cells. Accordingly, the aim of most traditional cancer therapies has been to destroy the transformed cells themselves. There is now widespread appreciation that the progressive growth and metastatic spread of cancer cells requires the cooperation of normal host cells (endothelial cells, fibroblasts, other mesenchymal cells, and immune cells), both local to, and at sites distant from, the site at which malignant transformation occurs. It is the balance of these cellular interactions that both determines the natural history of the cancer, and influences its response to therapy. This active tumor-host dynamic has stimulated interest in the tumor microenvironment as a key target for both cancer diagnosis and therapy. Recent data has demonstrated both that the presence of CD8(+) T cells within a tumor is associated with a good prognosis, and that the eradication of all malignantly transformed cells within a tumor requires that the intra-tumoral concentration of cytolytically active CD8(+) effector T cells remain above a critical concentration until every tumor cell has been killed. These findings have stimulated two initiatives in the field of cancer immunotherapy that focus on the tumor microenvironment. The first is the development of the immune score as part of the routine diagnostic and prognostic evaluation of human cancers, and the second is the development of combinatorial immune-based therapies that reduce tumor-associated immune suppression to unleash pre-existing or therapeutically-induced tumor immunity. In support of these efforts, the Society for the Immunotherapy of Cancer (SITC) is sponsoring a workshop entitled "Focus on the Target: The Tumor Microenvironment" to be held October 24-25, 2012 in Bethesda, Maryland. This meeting should support development of the immune score, and result in a position paper highlighting opportunities for the development of integrative cancer immunotherapies that sculpt the tumor microenvironment to promote definitive tumor rejection. C1 [Emens, Leisha A.] Johns Hopkins Univ, Sch Med, Tumor Immunol Program, Baltimore, MD 21231 USA. [Emens, Leisha A.] Johns Hopkins Univ, Sch Med, Breast Canc Res Program, Baltimore, MD 21231 USA. [Emens, Leisha A.] Johns Hopkins Univ, Sch Med, Dept Oncol, Baltimore, MD 21231 USA. [Silverstein, Samuel C.] Columbia Univ Coll Phys & Surg, Dept Physiol & Cellular Biophys, New York, NY 10032 USA. [Silverstein, Samuel C.] Columbia Univ Coll Phys & Surg, Dept Med, New York, NY 10032 USA. [Khleif, Samir] Georgia Hlth Sci Univ, Ctr Canc, Atlanta, GA USA. [Marincola, Francesco M.] NIH, IDIS, Bethesda, MD 20891 USA. [Marincola, Francesco M.] NIH, Dept Transfus Med, Ctr Clin, Bethesda, MD 20891 USA. [Marincola, Francesco M.] NIH, TransNIH Ctr Human Immunol CHI, Bethesda, MD 20891 USA. [Galon, Jerome] INSERM, UMRS872, Cordeliers Res Ctr, Lab Integrat Canc Immunol, F-75006 Paris, France. [Galon, Jerome] Georges Pompidou European Hosp, AP HP, Paris, France. [Galon, Jerome] Univ Paris 06, Paris, France. [Galon, Jerome] Univ Paris 05, Paris, France. [Emens, Leisha A.] Johns Hopkins Univ, Sidney Kimmel Comprehens Canc Ctr Johns Hopkins, Baltimore, MD 21231 USA. RP Emens, LA (reprint author), Johns Hopkins Univ, Sch Med, Tumor Immunol Program, Baltimore, MD 21231 USA. EM emensle@jhmi.edu NR 47 TC 21 Z9 22 U1 0 U2 7 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1479-5876 J9 J TRANSL MED JI J. Transl. Med. PD APR 10 PY 2012 VL 10 AR 70 DI 10.1186/1479-5876-10-70 PG 5 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 934CE UT WOS:000303417600001 PM 22490302 ER PT J AU Aldworth, ZN Stopfer, M AF Aldworth, Zane N. Stopfer, Mark TI Olfactory Coding: Tagging and Tuning Odor-Activated Synapses for Memory SO CURRENT BIOLOGY LA English DT Editorial Material ID EVOKED NEURAL OSCILLATIONS; MUSHROOM BODY; INFORMATION; DROSOPHILA; ASSEMBLIES; HONEYBEES; LOCUST; BRAIN C1 [Aldworth, Zane N.; Stopfer, Mark] NIH NICHD, Bethesda, MD 20892 USA. RP Aldworth, ZN (reprint author), NIH NICHD, Bldg 35,35 Lincoln Dr,Room 3A-102,Msc 3715, Bethesda, MD 20892 USA. EM stopferm@mail.nih.gov FU Intramural NIH HHS [Z99 HD999999]; NIDCD NIH HHS [F32 DC000234] NR 20 TC 2 Z9 4 U1 0 U2 9 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 0960-9822 J9 CURR BIOL JI Curr. Biol. PD APR 10 PY 2012 VL 22 IS 7 BP R227 EP R229 DI 10.1016/j.cub.2012.02.047 PG 3 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 926QC UT WOS:000302844900009 PM 22497937 ER PT J AU Stein, U Fleuter, C Siegel, F Smith, J Kopacek, A Scudiero, DA Hite, KM Schlag, PM Shoemaker, RH Walther, W AF Stein, U. Fleuter, C. Siegel, F. Smith, J. Kopacek, A. Scudiero, D. A. Hite, K. M. Schlag, P. M. Shoemaker, R. H. Walther, W. TI Impact of mutant beta-catenin on ABCB1 expression and therapy response in colon cancer cells SO BRITISH JOURNAL OF CANCER LA English DT Article DE colon cancer; beta-catenin; multidrug resistance; ABCB1; therapy response ID PRODUCT P-GLYCOPROTEIN; MULTIDRUG-RESISTANCE; COLORECTAL-CANCER; MULTIDRUG-RESISTANCE-1 GENE; MDR1 GENE; LINES; METASTASIS; MUTATIONS; CARCINOMA; CARCINOGENESIS AB BACKGROUND: Colorectal cancers are often chemoresistant toward antitumour drugs that are substrates for ABCB1-mediated multidrug resistance (MDR). Activation of the Wnt/beta-catenin pathway is frequently observed in colorectal cancers. This study investigates the impact of activated, gain-of-function beta-catenin on the chemoresistant phenotype. METHODS: The effect of mutant (mut) beta-catenin on ABCB1 expression and promoter activity was examined using HCT116 human colon cancer cells and isogenic sublines harbouring gain-of-function or wild-type beta-catenin, and patients' tumours. Chemosensitivity towards 24 anticancer drugs was determined by high throughput screening. RESULTS: Cell lines with mut beta-catenin showed high ABCB1 promoter activity and expression. Transfection and siRNA studies demonstrated a dominant role for the mutant allele in activating ABCB1 expression. Patients' primary colon cancer tumours shown to express the same mut beta-catenin allele also expressed high ABCB1 levels. However, cell line chemosensitivities towards 24 MDR-related and non-related antitumour drugs did not differ despite different beta-catenin genotypes. CONCLUSION: Although ABCB1 is dominantly regulated by mut beta-catenin, this did not lead to drug resistance in the isogenic cell line model studied. In patient samples, the same beta-catenin mutation was detected. The functional significance of the mutation for predicting patients' therapy response or for individualisation of chemotherapy regimens remains to be established. British Journal of Cancer (2012) 106, 1395-1405. doi: 10.1038/bjc.2012.81 www.bjcancer.com Published online 29 March 2012 (C) 2012 Cancer Research UK C1 [Stein, U.; Fleuter, C.; Siegel, F.; Smith, J.; Kopacek, A.; Walther, W.] Expt & Clin Res Ctr, D-13125 Berlin, Germany. [Scudiero, D. A.; Hite, K. M.] NCI, SAIC Frederick, Frederick, MD 21702 USA. [Schlag, P. M.] Charite, Charite Comprehens Canc Ctr, D-10117 Berlin, Germany. [Shoemaker, R. H.] NCI, Screening Technol Branch, Dev Therapeut Program, Div Canc Treatment & Diag, Frederick, MD 21702 USA. RP Stein, U (reprint author), Expt & Clin Res Ctr, D-13125 Berlin, Germany. EM ustein@mdc-berlin.de NR 52 TC 11 Z9 11 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 APR 10 PY 2012 VL 106 IS 8 BP 1395 EP 1405 DI 10.1038/bjc.2012.81 PG 11 WC Oncology SC Oncology GA 925SX UT WOS:000302782800006 PM 22460269 ER PT J AU Cook, NR Paynter, NP Eaton, CB Manson, JE Martin, LW Robinson, JG Rossouw, JE Wassertheil-Smoller, S Ridker, PM AF Cook, Nancy R. Paynter, Nina P. Eaton, Charles B. Manson, JoAnn E. Martin, Lisa W. Robinson, Jennifer G. Rossouw, Jacques E. Wassertheil-Smoller, Sylvia Ridker, Paul M. TI Comparison of the Framingham and Reynolds Risk Scores for Global Cardiovascular Risk Prediction in the Multiethnic Women's Health Initiative SO CIRCULATION LA English DT Article DE cardiovascular diseases; forecasting; prevention; models statistical; risk factors; statins; risk assessment ID C-REACTIVE PROTEIN; CORONARY-HEART-DISEASE; EVALUATING ROSUVASTATIN JUPITER; CASE-COHORT DESIGNS; PRIMARY PREVENTION; VALIDATION; MODELS; TRIAL; RECLASSIFICATION; JUSTIFICATION AB Background-Framingham-based and Reynolds Risk scores for cardiovascular disease (CVD) prediction have not been directly compared in an independent validation cohort. Methods and Results-We selected a case-cohort sample of the multiethnic Women's Health Initiative Observational Cohort, comprising 1722 cases of major CVD (752 myocardial infarctions, 754 ischemic strokes, and 216 other CVD deaths) and a random subcohort of 1994 women without prior CVD. We estimated risk using the Adult Treatment Panel III (ATP-III) score, the Reynolds Risk Score, and the Framingham CVD model, reweighting to reflect cohort frequencies. Predicted 10-year risk varied widely between models, with >= 10% risk in 6%, 10%, and 41% of women with the ATP-III, Reynolds, and Framingham CVD models, respectively. Calibration was adequate for the Reynolds model, but the ATP-III and Framingham CVD models overestimated risk for coronary heart disease and major CVD, respectively. After recalibration, the Reynolds model demonstrated improved discrimination over the ATP-III model through a higher c statistic (0.765 versus 0.757; P=0.03), positive net reclassification improvement (NRI; 4.9%; P=0.02), and positive integrated discrimination improvement (4.1%; P<0.0001) overall, excluding diabetics (NRI=4.2%; P=0.01), and in white (NRI=4.3%; P=0.04) and black (NRI=11.4%; P=0.13) women. The Reynolds (NRI=12.9%; P<0.0001) and ATP-III (NRI=5.9%; P=0.0001) models demonstrated better discrimination than the Framingham CVD model. Conclusions-The Reynolds Risk Score was better calibrated than the Framingham-based models in this large external validation cohort. The Reynolds score also showed improved discrimination overall and in black and white women. Large differences in risk estimates exist between models, with clinical implications for statin therapy. (Circulation. 2012; 125:1748-1756.) C1 [Cook, Nancy R.] Harvard Univ, Brigham & Womens Hosp, Div Prevent Med, Sch Med, Boston, MA 02215 USA. [Eaton, Charles B.] Brown Univ, Sch Med, Providence, RI 02912 USA. [Martin, Lisa W.] George Washington Univ, Sch Med, Washington, DC USA. [Robinson, Jennifer G.] Univ Iowa, Iowa City, IA USA. [Rossouw, Jacques E.] NHLBI, NIH, Bethesda, MD 20892 USA. [Wassertheil-Smoller, Sylvia] Albert Einstein Coll Med, Bronx, NY 10467 USA. RP Cook, NR (reprint author), Harvard Univ, Brigham & Womens Hosp, Div Prevent Med, Sch Med, 900 Commonwealth Ave E, Boston, MA 02215 USA. EM ncook@rics.bwh.harvard.edu OI Martin, Lisa Warsinger/0000-0003-4352-0914 FU National Heart, Lung, and Blood Institute's Broad Agency Announcement [HHSN268200960011C]; National Heart, Lung, and Blood Institute; National Institutes of Health; US Department of Health and Human Services [N01WH22110, 24152, 32100-2, 32105-6, 32108-9, 32111-13, 32115, 32118-9, 32122, 42107-26, 42129-32, 44221] FX This project was supported by National Heart, Lung, and Blood Institute's Broad Agency Announcement contract HHSN268200960011C. The Women's Health Initiative program is funded by the National Heart, Lung, and Blood Institute, National Institutes of Health, and the US Department of Health and Human Services through contracts N01WH22110, 24152, 32100-2, 32105-6, 32108-9, 32111-13, 32115, 32118-9, 32122, 42107-26, 42129-32, and 44221. NR 39 TC 85 Z9 87 U1 1 U2 15 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD APR 10 PY 2012 VL 125 IS 14 BP 1748 EP U112 DI 10.1161/CIRCULATIONAHA.111.075929 PG 20 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 925WR UT WOS:000302793300016 PM 22399535 ER PT J AU Kovacic, JC Mercader, N Torres, M Boehm, M Fuster, V AF Kovacic, Jason C. Mercader, Nadia Torres, Miguel Boehm, Manfred Fuster, Valentin TI Epithelial-to-Mesenchymal and Endothelial-to-Mesenchymal Transition From Cardiovascular Development to Disease SO CIRCULATION LA English DT Article DE endothelium; epithelium; development; endocardium; vasculature; cardiovascular diseases ID GROWTH-FACTOR-BETA; PLASMINOGEN-ACTIVATOR INHIBITOR-1; CORONARY-ARTERY FORMATION; CHRONIC PULMONARY-HYPERTENSION; TRANSCRIPTION FACTOR SNAIL; EPICARDIUM-DERIVED CELLS; CARDIAC-VALVE FORMATION; VASCULAR SMOOTH-MUSCLE; CHICK-EMBRYO; IN-VIVO C1 [Kovacic, Jason C.; Fuster, Valentin] Mt Sinai Sch Med, Zena & Michael A Wiener Cardiovasc Inst, New York, NY 10029 USA. [Mercader, Nadia; Torres, Miguel; Fuster, Valentin] CNIC, Madrid, Spain. [Boehm, Manfred] NHLBI, Ctr Mol Med, Bethesda, MD 20892 USA. [Fuster, Valentin] Mt Sinai Sch Med, Marie Josee & Henry R Kravis Cardiovasc Hlth Ctr, New York, NY USA. RP Kovacic, JC (reprint author), Mt Sinai Sch Med, Zena & Michael A Wiener Cardiovasc Inst, 1 Gustave L Levy Pl,Box 1030, New York, NY 10029 USA. EM jason.kovacic@mountsinai.org RI Mercader, Nadia/L-2728-2014; Torres, Miguel/A-7388-2013; Fuster, Valentin/H-4319-2015 OI Mercader, Nadia/0000-0002-0905-6399; Torres, Miguel/0000-0003-0906-4767; Fuster, Valentin/0000-0002-9043-9986 FU National Institutes of Health [1K08HL111330-01, 5U01HL071988-07]; Fundacion Centro Nacional de Investigaciones Cardiovasculares Carlos III; Spanish Ministry of Economy and Competitiveness [BFU200800212/BMC, BFU2011-25297, RYC-2006-001694]; Comunidad de Madrid [S2011/BMD-2321]; Spanish 'Ministerio de Economia y Competitividad'; Instituto de Salud Carlos III; proCNIC foundation; National Heart, Lung and Blood Institute FX Dr Kovacic is supported by National Institutes of Health grant 1K08HL111330-01. Dr Mercader is supported by the Fundacion Centro Nacional de Investigaciones Cardiovasculares Carlos III, the Spanish Ministry of Economy and Competitiveness (BFU200800212/BMC, BFU2011-25297, and RYC-2006-001694) as well as the Comunidad de Madrid (S2011/BMD-2321). Dr Torres is funded by grants from the Spanish 'Ministerio de Economia y Competitividad'. CNIC is funded by the Instituto de Salud Carlos III and the proCNIC foundation. Dr Boehm is supported by the intramural research program of the National Heart, Lung and Blood Institute. Dr Fuster is in receipt of National Institutes of Health grant 5U01HL071988-07. NR 160 TC 88 Z9 90 U1 2 U2 30 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD APR 10 PY 2012 VL 125 IS 14 BP 1795 EP 1808 DI 10.1161/CIRCULATIONAHA.111.040352 PG 14 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 925WR UT WOS:000302793300021 PM 22492947 ER PT J AU Glancy, B Balaban, RS AF Glancy, Brian Balaban, Robert S. TI Role of Mitochondrial Ca2+ in the Regulation of Cellular Energetics SO BIOCHEMISTRY LA English DT Article ID PYRUVATE-DEHYDROGENASE PHOSPHATASE; RAT-LIVER MITOCHONDRIA; CYTOCHROME-C-OXIDASE; NICOTINAMIDE ADENINE-DINUCLEOTIDE; NUCLEAR-MAGNETIC-RESONANCE; KIDNEY ALPHA-KETOGLUTARATE; POSITIVE INOTROPIC AGENTS; CALCIUM-BINDING PROTEIN; BROWN ADIPOSE-TISSUE; OXIDATIVE-PHOSPHORYLATION AB Calcium is an important signaling molecule involved in the regulation of many cellular functions. The large free energy in the Ca2+ ion membrane gradients makes Ca2+ signaling inherently sensitive to the available cellular free energy, primarily in the form of ATP. In addition, Ca2+ regulates many cellular ATP-consuming reactions such as muscle contraction, exocytosis, biosynthesis, and neuronal signaling. Thus, Ca2+ becomes a logical candidate as a signaling molecule for modulating ATP hydrolysis and synthesis during changes in numerous forms of cellular work Mitochondria are the primary source of aerobic energy production in mammalian cells and also maintain a large Ca2+ gradient across their inner membrane, providing a signaling potential for this molecule. The demonstrated link between cytosolic and mitochondrial Ca2+ concentrations, identification of transport mechanisms, and the proximity of mitochondria to Ca2+ release sites further supports the notion that Ca2+ can be an important signaling molecule in the energy metabolism interplay of the cytosol with the mitochondria. Here we review sites within the mitochondria where Ca2+ plays a role in the regulation of ATP generation and potentially contributes to the orchestration of cellular metabolic homeostasis. Early work on isolated enzyme's pointed to several matrix dehydrogenases that are stimulated by Ca2+, which were confirmed in the intact mitochondrion as well as cellular and in vivo systems. However, studies in these intact systems suggested a more expansive influence of Ca2+ on mitochondrial energy conversion. Numerous noninvasive approaches monitoring NADH, mitochondrial membrane potential, oxygen consumption, and workloads suggest significant effects of Ca2+ on other elements of NADH generation as well as downstream elements of oxidative phosphorylation, including the F1Fo-ATPase and the cytochrome chain. These other potential elements of Ca2+ modification of mitochondrial energy conversion will be the focus of this review. Though most specific molecular mechanisms have yet to be elucidated, it is clear that Ca2+ provides a balanced activation of mitochondrial energy metabolism that exceeds the alteration of dehydrogenases alone. C1 [Glancy, Brian; Balaban, Robert S.] NHLBI, Cardiac Energet Lab, NIH, Bethesda, MD 20817 USA. RP Balaban, RS (reprint author), NHLBI, Cardiac Energet Lab, NIH, Bethesda, MD 20817 USA. EM rsb@nih.gov RI Glancy, Brian/P-3163-2016 OI Glancy, Brian/0000-0002-8571-244X FU Intramural NIH HHS [ZIA HL004601-23, ZIA HL004610-03] NR 173 TC 151 Z9 153 U1 1 U2 30 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0006-2960 J9 BIOCHEMISTRY-US JI Biochemistry PD APR 10 PY 2012 VL 51 IS 14 BP 2959 EP 2973 DI 10.1021/bi2018909 PG 15 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 921NL UT WOS:000302484200001 PM 22443365 ER PT J AU Connelly, L Jang, H Arce, FT Ramachandran, S Kagan, BL Nussinov, R Lal, R AF Connelly, Laura Jang, Hyunbum Arce, Fernando Teran Ramachandran, Srinivasan Kagan, Bruce L. Nussinov, Ruth Lal, Ratnesh TI Effects of Point Substitutions on the Structure of Toxic Alzheimer's beta-Amyloid Channels: Atomic Force Microscopy and Molecular Dynamics Simulations SO BIOCHEMISTRY LA English DT Article ID FORMS ION CHANNELS; ALL-D-ENANTIOMER; IN-VITRO; PROTEIN; DISEASE; PEPTIDE; FIBRILS; MUTAGENESIS; PORES; A-BETA-42 AB Alzheimer's disease (AD) is a misfolded protein disease characterized by the accumulation of beta-amyloid (A beta) peptide as senile plaques, progressive neurodegeneration, and memory loss. Recent evidence suggests that AD pathology is linked to the destabilization of cellular ionic homeostasis mediated by toxic pores made of A beta peptides. Understanding the exact nature by which these pores conduct electrical and molecular signals could aid in identifying potential therapeutic targets for the prevention and treatment of AD. Here using atomic force microscopy (AFM) and molecular dynamics (MD) simulations, we compared the imaged pore structures with models to predict channel conformations as a function of amino acid sequence. Site-specific amino acid (AA) substitutions in the wild-type A beta(1-42) peptide yield information regarding the location and significance of individual AA residues to its characteristic structure activity relationship. We selected two AAs that our MD simulation predicted to inhibit or permit pore conductance. The substitution of Phe19 with Pro has previously been shown to eliminate conductance in the planar lipid bilayer system. Our MD simulations predict a channel-like shape with a collapsed pore, which is supported by the AFM channel images. We suggest that proline, a known beta-sheet breaker, creates a kink in the center of the pore and prevents conductance via blockage. This residue may be a viable target for drug development studies aiming to inhibit A beta from inducing ionic destabilization toxicity. The substitution of Phe20 with Cys exhibits pore structures indistinguishable from the wild type in AFM images. MD simulations predict site 20 to face the solvated pore. Overall, the mutations support the previously predicted beta-sheet-based channel structure. C1 [Jang, Hyunbum; Nussinov, Ruth] SAIC Frederick Inc, Basic Sci Program, Ctr Canc Res Nanobiol Program, Frederick Natl Lab Canc Res, Frederick, MD 21702 USA. [Connelly, Laura; Arce, Fernando Teran; Ramachandran, Srinivasan; Lal, Ratnesh] Univ Calif San Diego, Mat Sci Program, La Jolla, CA 92093 USA. [Connelly, Laura; Arce, Fernando Teran; Ramachandran, Srinivasan; Lal, Ratnesh] Univ Calif San Diego, Dept Bioengn, La Jolla, CA 92093 USA. [Connelly, Laura; Arce, Fernando Teran; Ramachandran, Srinivasan; Lal, Ratnesh] Univ Calif San Diego, Dept Mech & Aerosp Engn, La Jolla, CA 92093 USA. [Kagan, Bruce L.] Univ Calif Los Angeles, Dept Psychiat, David Geffen Sch Med, Semel Inst Neurosci & Human Behav, Los Angeles, CA 90024 USA. [Nussinov, Ruth] Tel Aviv Univ, Sackler Sch Med, Dept Human Mol Genet & Biochem, IL-69978 Tel Aviv, Israel. RP Nussinov, R (reprint author), SAIC Frederick Inc, Basic Sci Program, Ctr Canc Res Nanobiol Program, Frederick Natl Lab Canc Res, Frederick, MD 21702 USA. EM ruthnu@helix.nih.gov; rlal@ucsd.edu RI Ramachandran, Srinivasan/G-5300-2010 OI Ramachandran, Srinivasan/0000-0002-4912-0279 FU National Institutes of Health (National Institute on Aging) [AG028709]; Frederick National Laboratory for Cancer Research; National Institutes of Health [HHSN261200800001E]; National Institutes of Health, Frederick National Lab, Center for Cancer Research FX This research was supported by the National Institutes of Health (National Institute on Aging Grant AG028709 to R.L.). This project has been funded in whole or in part with Federal funds from the Frederick National Laboratory for Cancer Research, National Institutes of Health, under Contract HHSN261200800001E. This research was supported (in part) by the Intramural Research Program of the National Institutes of Health, Frederick National Lab, Center for Cancer Research. NR 43 TC 28 Z9 29 U1 4 U2 41 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0006-2960 J9 BIOCHEMISTRY-US JI Biochemistry PD APR 10 PY 2012 VL 51 IS 14 BP 3031 EP 3038 DI 10.1021/bi300257e PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 921NL UT WOS:000302484200007 PM 22413858 ER PT J AU Do Kwon, Y Finzi, A Wu, XL Dogo-Isonagie, C Lee, LK Moore, LR Schmidt, SD Stuckey, J Yang, YP Zhou, TQ Zhu, J Vicic, DA Debnath, AK Shapiro, L Bewley, CA Mascola, JR Sodroski, JG Kwong, PD AF Do Kwon, Young Finzi, Andres Wu, Xueling Dogo-Isonagie, Cajetan Lee, Lawrence K. Moore, Lucas R. Schmidt, Stephen D. Stuckey, Jonathan Yang, Yongping Zhou, Tongqing Zhu, Jiang Vicic, David A. Debnath, Asim K. Shapiro, Lawrence Bewley, Carole A. Mascola, John R. Sodroski, Joseph G. Kwong, Peter D. TI Unliganded HIV-1 gp120 core structures assume the CD4-bound conformation with regulation by quaternary interactions and variable loops SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE conformational equilibrium; viral evasion; X-ray crystallography ID VIRAL MEMBRANE-FUSION; ENVELOPE GLYCOPROTEIN; NEUTRALIZATION SENSITIVITY; MONOCLONAL-ANTIBODIES; VIRUS; CD4; BINDING; REVEALS; ENTRY; ARCHITECTURE AB The HIV-1 envelope (Env) spike (gp120(3)/gp41(3)) undergoes considerable structural rearrangements to mediate virus entry into cells and to evade the host immune response. Engagement of CD4, the primary human receptor, fixes a particular conformation and primes Env for entry. The CD4-bound state, however, is prone to spontaneous inactivation and susceptible to antibody neutralization. How does unliganded HIV-1 maintain CD4-binding capacity and regulate transitions to the CD4-bound state? To define this mechanistically, we determined crystal structures of unliganded core gp120 from HIV-1 clades B, C, and E. Notably, all of these unliganded HIV-1 structures resembled the CD4-bound state. Conformational fixation with ligand selection and thermodynamic analysis of full-length and core gp120 interactions revealed that the tendency of HIV-1 gp120 to adopt the CD4-bound conformation was restrained by the V1/V2- and V3-variable loops. In parallel, we determined the structure of core gp120 in complex with the small molecule, NBD-556, which specifically recognizes the CD4-bound conformation of gp120. Neutralization by NBD-556 indicated that Env spikes on primary isolates rarely assume the CD4-bound conformation spontaneously, although they could do so when quaternary restraints were loosened. Together, the results suggest that the CD4-bound conformation represents a "ground state" for the gp120 core, with variable loop and quaternary interactions restraining unliganded gp120 from "snapping" into this conformation. A mechanism of control involving deformations in unliganded structure from a functionally critical state (e. g., the CD4-bound state) provides advantages in terms of HIV-1 Env structural diversity and resistance to antibodies and inhibitors, while maintaining elements essential for entry. C1 [Finzi, Andres; Sodroski, Joseph G.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Canc Immunol & AIDS,Dept Pathol,Div AIDS, Boston, MA 02115 USA. [Do Kwon, Young; Wu, Xueling; Schmidt, Stephen D.; Stuckey, Jonathan; Yang, Yongping; Zhou, Tongqing; Zhu, Jiang; Shapiro, Lawrence; Mascola, John R.; Kwong, Peter D.] NIAID, Vaccine Res Ctr, NIH, Bethesda, MD 20892 USA. [Sodroski, Joseph G.] Harvard Univ, Sch Publ Hlth, Dept Immunol & Infect Dis, Boston, MA 02115 USA. [Dogo-Isonagie, Cajetan; Bewley, Carole A.] NIDDKD, Bioorgan Chem Lab, NIH, Bethesda, MD 20892 USA. [Lee, Lawrence K.] Victor Chang Cardiac Res Inst, Struct & Computat Biol Div, Darlinghurst, NSW 2010, Australia. [Moore, Lucas R.; Vicic, David A.] Univ Arkansas, Dept Chem & Biochem, Fayetteville, AR 72701 USA. [Vicic, David A.] Univ Hawaii, Dept Chem, Honolulu, HI 96822 USA. [Debnath, Asim K.] New York Blood Ctr, Lindsley F Kimball Res Inst, Lab Mol Modeling & Drug Design, New York, NY 10065 USA. [Shapiro, Lawrence] Columbia Univ, Dept Biochem & Mol Biophys, New York, NY 10032 USA. RP Sodroski, JG (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Canc Immunol & AIDS,Dept Pathol,Div AIDS, 44 Binney St, Boston, MA 02115 USA. EM joseph_sodroski@dfci.harvard.edu; pdkwong@nih.gov RI Kwon, Young Do/A-6957-2010; Zhou, Tongqing/A-6880-2010; Cheng, Yushao/E-6256-2011; Schmidt, Stephen/B-5398-2012 OI Zhou, Tongqing/0000-0002-3935-4637; FU National Institutes of Health (NIH); International AIDS Vaccine Initiative's Neutralizing Antibody Consortium; US Department of Energy, Basic Energy Sciences, Office of Science [W-31-109-Eng-38] FX We thank J. Hoxie, R. Sandier, I. A. Wilson, and members of the Structural Biology Section and Structural Bioinformatics Core, Vaccine Research Center, for discussions and comments on the manuscript. Support for this work was provided by the Intramural Research Program of the National Institutes of Health (NIH) and by grants from the NIH and from the International AIDS Vaccine Initiative's Neutralizing Antibody Consortium. Use of sector 22 (Southeast Region Collaborative Access Team) at the Advanced Photon Source was supported by the US Department of Energy, Basic Energy Sciences, Office of Science Contract W-31-109-Eng-38. NR 46 TC 117 Z9 117 U1 3 U2 31 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD APR 10 PY 2012 VL 109 IS 15 BP 5663 EP 5668 DI 10.1073/pnas.1112391109 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 922FX UT WOS:000302533500028 ER PT J AU Baron, BW Anastasi, J Hyjek, EM Bies, J Reddy, PL Dong, JF Joseph, L Thirman, MJ Wroblewski, K Wolff, L Baron, JM AF Baron, Beverly W. Anastasi, John Hyjek, Elizabeth M. Bies, Juraj Reddy, Poluru L. Dong, Jingfang Joseph, Loren Thirman, Michael J. Wroblewski, Kristen Wolff, Linda Baron, Joseph M. TI PIM1 gene cooperates with human BCL6 gene to promote the development of lymphomas SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID B-CELL LYMPHOMA; GERMINAL-CENTER FORMATION; BURKITTS-LYMPHOMA; C-MYC; EXPRESSION; DIFFERENTIATION; PROTOONCOGENE; KINASE; LEUKEMIA; ACTIVATION AB Diffuse large B-cell lymphomas in humans are associated with chromosomal rearrangements (similar to 40%) and/or mutations disrupting autoregulation (similar to 16%) involving the BCL6 gene. Studies of lymphoma development in humans and mouse models have indicated that lymphomagenesis evolves through the accumulation of multiple genetic alterations. Based on our prior studies, which indicated that carcinogen-induced DNA mutations enhance the incidence of lymphomas in our mouse model expressing a human BCL6 transgene, we hypothesized that mutated genes are likely to play an important cooperative role in BCL6-associated lymphoma development. We used retroviral insertional mutagenesis in an effort to identify which genes cooperate with BCL6 in lymphomagenesis in our BCL6 transgenic mice. We identified PIM1 as the most frequently recurring cooperating gene in our murine BCL6-associated lymphomas (T- and B-cell types), and we observed elevated levels of PIM1 mRNA and protein expression in these neoplasms. Further, immunohistochemical staining, which was performed in 20 randomly selected BCL6-positive human B-and T-cell lymphomas, revealed concurrent expression of BCL6 and PIM1 in these neoplasms. As PIM1 encodes a serine/threonine kinase, PIM1 kinase inhibition may be a promising therapy for BCL6/PIM1-positive human lymphomas. C1 [Baron, Beverly W.; Anastasi, John; Hyjek, Elizabeth M.; Reddy, Poluru L.; Joseph, Loren] Univ Chicago, Dept Pathol, Chicago, IL 60637 USA. [Bies, Juraj; Wolff, Linda] NCI, Leukemogenesis Sect, Cellular Oncol Lab, NIH, Bethesda, MD 20892 USA. [Dong, Jingfang; Thirman, Michael J.; Baron, Joseph M.] Univ Chicago, Dept Med, Chicago, IL 60637 USA. [Wroblewski, Kristen] Univ Chicago, Dept Hlth Studies, Chicago, IL 60637 USA. RP Baron, BW (reprint author), Univ Chicago, Dept Pathol, 5841 S Maryland Ave, Chicago, IL 60637 USA. EM beverly.baron@uchospitals.edu FU Department of Pathology at the University of Chicago; University of Chicago Cancer Center [P30 CA014599]; University of Chicago FX We thank Dr. B. Gladstone for technical assistance, Dr. I. Aifantis for antibodies for flow cytometry, D. Kane for expertise in immunohistochemistry, R. Duggan for assistance with FACS, and G. Musa for assistance with illustrations. This work was supported by the Department of Pathology at the University of Chicago (B. W. B.), University of Chicago Cancer Center Support Grant P30 CA014599 (to B. W. B.), and Hematology Research Funds at the University of Chicago donated by S. Samsky and E. Lanzl (to J.M.B.). NR 45 TC 9 Z9 9 U1 0 U2 3 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD APR 10 PY 2012 VL 109 IS 15 BP 5735 EP 5739 DI 10.1073/pnas.1201168109 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 922FX UT WOS:000302533500040 PM 22451912 ER PT J AU Chang, YF Lee-Chang, JS Imam, JS Buddavarapu, KC Subaran, SS Sinha-Hikim, AP Gorospe, M Rao, MK AF Chang, Yao-Fu Lee-Chang, Jennifer S. Imam, J. Saadi Buddavarapu, Kalyan Chakravarthy Subaran, Sarah S. Sinha-Hikim, Amiya P. Gorospe, Myriam Rao, Manjeet K. TI Interaction between microRNAs and actin-associated protein Arpc5 regulates translational suppression during male germ cell differentiation SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE spermiogenesis; messenger ribonucleoprotein; Arp2/3; processing body ID RNA-BINDING-PROTEIN; SPERMATOGENIC CELLS; TRANSITION PROTEINS; ARP2/3 COMPLEX; MESSENGER-RNA; MOUSE; MICE; PHOSPHORYLATION; SPERMATIDS; SERTOLI AB Decoupling of transcription and translation during postmeiotic germ cell differentiation is critical for successful spermatogenesis. Here we establish that the interaction between microRNAs and actin-associated protein Arpc5 sets the stage for an elaborate translational control mechanism by facilitating the sequestration of germ cell mRNAs into translationally inert ribonucleoprotein particles until they are later translated. Our studies reveal that loss of microRNA-dependent regulation of Arpc5, which controls the distribution of germ cell mRNAs between translationally active and inactive pools, results in abnormal round spermatid differentiation and impaired fertility. Interestingly, Arpc5 functions as a broadly acting translational suppressor, as it inhibits translation initiation by blocking 80S formation and facilitates the transport of mRNAs to chromatoid/P bodies. These findings identify a unique role for actin-associated proteins in translational regulation, and suggest that mRNA-specific and general translational control mechanisms work in tandem to regulate critical germ cell differentiation events and diverse somatic cell functions. C1 [Chang, Yao-Fu; Lee-Chang, Jennifer S.; Imam, J. Saadi; Buddavarapu, Kalyan Chakravarthy; Rao, Manjeet K.] Univ Texas Hlth Sci Ctr San Antonio, Greehey Childrens Canc Res Inst, San Antonio, TX 78229 USA. [Chang, Yao-Fu; Rao, Manjeet K.] Univ Texas Hlth Sci Ctr San Antonio, Dept Cellular & Struct Biol, San Antonio, TX 78229 USA. [Subaran, Sarah S.; Gorospe, Myriam] NIA, Lab Mol Biol & Immunol, Intramural Res Program, NIH, Baltimore, MD 21224 USA. [Sinha-Hikim, Amiya P.] Charles R Drew Univ Med & Sci, Div Endocrinol Metab & Mol Med, Los Angeles, CA 90059 USA. RP Rao, MK (reprint author), Univ Texas Hlth Sci Ctr San Antonio, Greehey Childrens Canc Res Inst, San Antonio, TX 78229 USA. EM raom@uthscsa.edu OI Imam, J Saadi/0000-0003-3463-838X FU National Institute of Child Health and Human Development [HD057118]; National Institutes of Health (NIH); National Institute on Aging, NIH FX We thank Yidong Chen, Krystle Harris, Jennifer Rebeles, and Jennifer Martindale for assistance with experiments and evaluation of data. We also thank Daniel Schoenberg, Rod Balhorn, Marvin Fritzler, and Peter Sarnow for generously providing us with reagents. Thanks to Alexander Pertsemlidis for critical reading of the manuscript. M. K. R. was supported by National Institute of Child Health and Human Development Grant HD057118, National Institutes of Health (NIH); and S. S. S. and M. G. were supported by the Intramural Research Program, National Institute on Aging, NIH. NR 29 TC 14 Z9 15 U1 0 U2 1 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD APR 10 PY 2012 VL 109 IS 15 BP 5750 EP 5755 DI 10.1073/pnas.1117837109 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 922FX UT WOS:000302533500043 PM 22447776 ER PT J AU Vertes, PE Alexander-Bloch, AF Gogtay, N Giedd, JN Rapoport, JL Bullmore, ET AF Vertes, Petra E. Alexander-Bloch, Aaron F. Gogtay, Nitin Giedd, Jay N. Rapoport, Judith L. Bullmore, Edward T. TI Simple models of human brain functional networks SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE neuroimaging; graph theory; systems; trade-off ID SMALL-WORLD NETWORKS; GRAPH-THEORETICAL ANALYSIS; COMMON STEREOTACTIC SPACE; GLOBAL OPTIMIZATION; SCHIZOPHRENIA; CONNECTIVITY; SYSTEMS; IMAGES; ROBUST; REGISTRATION AB Human brain functional networks are embedded in anatomical space and have topological properties-small-worldness, modularity, fat-tailed degree distributions-that are comparable to many other complex networks. Although a sophisticated set of measures is available to describe the topology of brain networks, the selection pressures that drive their formation remain largely unknown. Here we consider generative models for the probability of a functional connection (an edge) between two cortical regions (nodes) separated by some Euclidean distance in anatomical space. In particular, we propose a model in which the embedded topology of brain networks emerges from two competing factors: a distance penalty based on the cost of maintaining long-range connections; and a topological term that favors links between regions sharing similar input. We show that, together, these two biologically plausible factors are sufficient to capture an impressive range of topological properties of functional brain networks. Model parameters estimated in one set of functional MRI (fMRI) data on normal volunteers provided a good fit to networks estimated in a second independent sample of fMRI data. Furthermore, slightly detuned model parameters also generated a reasonable simulation of the abnormal properties of brain functional networks in people with schizophrenia. We therefore anticipate that many aspects of brain network organization, in health and disease, may be parsimoniously explained by an economical clustering rule for the probability of functional connectivity between different brain areas. C1 [Vertes, Petra E.; Alexander-Bloch, Aaron F.; Bullmore, Edward T.] Univ Cambridge, Behav & Clin Neurosci Inst, Dept Psychiat, Cambridge CB2 0SZ, England. [Alexander-Bloch, Aaron F.; Gogtay, Nitin; Giedd, Jay N.; Rapoport, Judith L.] NIMH, Child Psychiat Branch, Bethesda, MD 20892 USA. [Alexander-Bloch, Aaron F.] Univ Calif Los Angeles, David Geffen Sch Med, Los Angeles, CA 90095 USA. [Bullmore, Edward T.] Cambridgeshire & Peterborough Natl Hlth Serv Fdn, Cambridge CB21 5EF, England. [Bullmore, Edward T.] Addenbrookes Hosp, GlaxoSmithKline Clin Unit Cambridge, Cambridge CB2 0QQ, England. RP Bullmore, ET (reprint author), Univ Cambridge, Behav & Clin Neurosci Inst, Dept Psychiat, Cambridge CB2 0SZ, England. EM etb23@cam.ac.uk RI Giedd, Jay/B-7302-2012; Giedd, Jay/J-9644-2015; Bullmore, Edward/C-1706-2012; OI Giedd, Jay/0000-0003-0827-3460; Giedd, Jay/0000-0003-2002-8978; Bullmore, Edward/0000-0002-8955-8283; Alexander-Bloch, Aaron/0000-0001-6554-1893; Vertes, Petra E./0000-0002-0992-3210 FU Wellcome Trust; Medical Research Council; Engineering and Physical Sciences Research Council; NIH FX The Behavioural and Clinical Neuroscience Institute is supported by the Wellcome Trust and the Medical Research Council. P. E. V. was supported by a grant from the Engineering and Physical Sciences Research Council. Data collection was supported by the intramural research program of the National Institute of Mental Health, NIH. A.F.A.-B. is supported by the NIH Cambridge Graduate Partnership Program. NR 52 TC 87 Z9 89 U1 3 U2 18 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD APR 10 PY 2012 VL 109 IS 15 BP 5868 EP 5873 DI 10.1073/pnas.1111738109 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 922FX UT WOS:000302533500063 PM 22467830 ER PT J AU Gaiser, MR Lammermann, T Feng, X Igyarto, BZ Kaplan, DH Tessarollo, L Germain, RN Udey, MC AF Gaiser, Maria R. Laemmermann, Tim Feng, Xu Igyarto, Botond Z. Kaplan, Daniel H. Tessarollo, Lino Germain, Ronald N. Udey, Mark C. TI Cancer-associated epithelial cell adhesion molecule (EpCAM; CD326) enables epidermal Langerhans cell motility and migration in vivo SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID DERMAL DENDRITIC CELLS; CONTACT HYPERSENSITIVITY; E-CADHERIN; EP-CAM; DEFICIENT MICE; STEM-CELLS; NULL MICE; RESPONSES; MATURATION; DISTINCT AB After activation, Langerhans cells (LC), a distinct subpopulation of epidermis-resident dendritic cells, migrate from skin to lymph nodes where they regulate the magnitude and quality of immune responses initiated by epicutaneously applied antigens. Modulation of LC-keratinocyte adhesion is likely to be central to regulation of LC migration. LC express high levels of epithelial cell adhesion molecule (EpCAM; CD326), a cell-surface protein that is characteristic of some epithelia and many carcinomas and that has been implicated in intercellular adhesion and metastasis. To gain insight into EpCAM function in a physiologic context in vivo, we generated conditional knockout mice with EpCAM-deficient LC and characterized them. Epidermis from these mice contained increased numbers of LC with normal levels of MHC and costimulatory molecules and T-cell-stimulatory activity in vitro. Migration of EpCAM-deficient LC from skin explants was inhibited, but chemotaxis of dissociated LC was not. Correspondingly, the ability of contact allergen-stimulated, EpCAM-deficient LC to exit epidermis in vivo was delayed, and strikingly fewer hapten-bearing LC subsequently accumulated in lymph nodes. Attenuated migration of EpCAM-deficient LC resulted in enhanced contact hypersensitivity responses as previously described in LC-deficient mice. Intravital microscopy revealed reduced translocation and dendrite motility in EpCAM-deficient LC in vivo in contact allergen-treated mice. These results conclusively link EpCAM expression to LC motility/migration and LC migration to immune regulation. EpCAM appears to promote LC migration from epidermis by decreasing LC-keratinocyte adhesion and may modulate intercellular adhesion and cell movement within in epithelia during development and carcinogenesis in an analogous fashion. C1 [Gaiser, Maria R.; Feng, Xu; Udey, Mark C.] NCI, Dermatol Branch, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. [Laemmermann, Tim; Germain, Ronald N.] NIAID, Lymphocyte Biol Sect, Lab Syst Biol, NIH, Bethesda, MD 20892 USA. [Igyarto, Botond Z.; Kaplan, Daniel H.] Univ Minnesota, Dept Dermatol, Ctr Immunol, Minneapolis, MN 55455 USA. [Tessarollo, Lino] NCI, Mouse Canc Genet Program, Ctr Canc Res, NIH, Frederick, MD 21702 USA. RP Udey, MC (reprint author), NCI, Dermatol Branch, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. EM udey@helix.nih.gov RI Kaplan, Daniel/N-2779-2013 OI Kaplan, Daniel/0000-0002-7851-7320 FU Center for Cancer Research, National Cancer Institute; National Institues of Allergy and Infectious Diseases, National Institutes of Health; National Institutes of Health [R01-AR056632]; International Human Frontier Science Program fellowship FX We thank Drs. William Telford and Michael Kruhlak for their advice and assistance with flow cytometry and conventional microscopy; Joshua Drago, Mallorie Heneghan, and Olga Milgrom for mouse husbandry and genotyping; Jay Linton, Michael Lu, Dr. Chuanjin Wu, and Dr. Sei-ichiro Motegi for advice and assistance with experimental procedures; and Dr. Stephen I. Katz for helpful discussions. This work was supported by the Intramural Research Program, Center for Cancer Research, National Cancer Institute, and the National Institues of Allergy and Infectious Diseases, National Institutes of Health, by National Institutes of Health Grant R01-AR056632 (to D.H.K.), and an International Human Frontier Science Program fellowship grant (to T.L.). NR 57 TC 29 Z9 30 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 APR 10 PY 2012 VL 109 IS 15 BP E889 EP E897 DI 10.1073/pnas.1117674109 PG 9 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 922FX UT WOS:000302533500005 PM 22411813 ER PT J AU Safaeian, M Hildesheim, A Gonzalez, P Yu, K Porras, C Li, QZ Rodriguez, AC Sherman, ME Schiffman, M Wacholder, S Burk, R Herrero, R Burdette, L Chanock, SJ Wang, SS AF Safaeian, Mahboobeh Hildesheim, Allan Gonzalez, Paula Yu, Kai Porras, Carolina Li, Qizhai Cecilia Rodriguez, Ana Sherman, Mark E. Schiffman, Mark Wacholder, Sholom Burk, Robert Herrero, Rolando Burdette, Laurie Chanock, Stephen J. Wang, Sophia S. TI Single Nucleotide Polymorphisms in the PRDX3 and RPS19 and Risk of HPV Persistence and Cervical Precancer/Cancer SO PLOS ONE LA English DT Article ID HUMAN-PAPILLOMAVIRUS INFECTION; FAMILY-CANCER DATABASE; COSTA-RICA; NEOPLASIA; PROGRESSION; VARIANTS; GENES AB Background: Host genetic factors might affect the risk of progression from infection with carcinogenic human papillomavirus (HPV), the etiologic agent for cervical cancer, to persistent HPV infection, and hence to cervical precancer and cancer. Methodology/Principal Findings: We assessed 18,310 tag single nucleotide polymorphisms (SNPs) from 1113 genes in 416 cervical intraepithelial neoplasia 3 (CIN3)/cancer cases, 356 women with persistent carcinogenic HPV infection (median persistence of 25 months) and 425 randomly selected women (non-cases and non-HPV persistent) from the 10,049 women from the Guanacaste, Costa Rica HPV natural history cohort. For gene and SNP associations, we computed age-adjusted odds ratio and p-trend. Three comparisons were made: 1) association with CIN3/cancer (compared CIN3/cancer cases to random controls), 2) association with persistence (compared HPV persistence to random controls), and 3) progression (compared CIN3/cancers with HPV-persistent group). Regions statistically significantly associated with CIN3/cancer included genes for peroxiredoxin 3 PRDX3, and ribosomal protein S19 RPS19. The single most significant SNPs from each gene associated with CIN3/cancer were PRDX3 rs7082598 (P-trend < 0.0001), and RPS19 rs2305809 (P-trend = 0.0007), respectively. Both SNPs were also associated with progression. Conclusions/Significance: These data suggest involvement of two genes, RSP19 and PRDX3, or other SNPs in linkage disequilibrium, with cervical cancer risk. Further investigation showed that they may be involved in both the persistence and progression transition stages. Our results require replication but, if true, suggest a role for ribosomal dysfunction, mitochondrial processes, and/or oxidative stress, or other unknown function of these genes in cervical carcinogenesis. C1 [Safaeian, Mahboobeh; Hildesheim, Allan; Yu, Kai; Sherman, Mark E.; Schiffman, Mark; Wacholder, Sholom] NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. [Gonzalez, Paula; Porras, Carolina; Cecilia Rodriguez, Ana; Herrero, Rolando] Fdn INCIENSA, Proyecto Epidemiol Guanacaste, San Jose, Costa Rica. [Li, Qizhai] Chinese Acad Sci, Acad Math & Syst Sci, Beijing, Peoples R China. [Burk, Robert] Albert Einstein Coll Med, Bronx, NY 10467 USA. [Burdette, Laurie; Chanock, Stephen J.] NCI Frederick, Core Genotyping Facil, Div Canc Epidemiol & Genet, Adv Technol Program,SAIC Frederick Inc, Frederick, MD USA. [Wang, Sophia S.] City Hope Natl Med Ctr, Dept Populat Sci, Div Etiol, Duarte, CA USA. RP Safaeian, M (reprint author), NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. EM safaeianm@mail.nih.gov RI Hildesheim, Allan/B-9760-2015 OI Hildesheim, Allan/0000-0003-0257-2363 FU NCI; NIH Office of Research On Women's Health; National Young Science Foundation of China [10901155]; SAIC-Frederick Inc.; Information Management Services, Inc. FX The study was funded by intramural NCI and the NIH Office of Research On Women's Health. The authors are grateful to Sabrina Chen from the Information Management Services, Inc. (IMS) for data management and programming support. They are also grateful to Amy Hutchinson and Belynda Hicks for their management of this genotyping effort at the NCI Core Genotyping Facility and for their scientific contributions to the authors' research efforts. Q. Li is partially supported by National Young Science Foundation of China No. 10901155. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.; Laurie Burdette and Stephen J. Chanock are employed by The Core Genotyping Facility (CGF) which is within the Division of Cancer Epidemiology and Genetics (DCEG) of the National Cancer Institute (NCI) and supported by SAIC-Frederick Inc. Information Management Services, Inc. also supported this study, along with Amy Hutchinson and Belynda Hicks with their management of this genotyping effort at the NCI Core Genotyping Facility and for their scientific contributions to the authors' research efforts. This does not alter the authors' adherence to all PloS ONE policies on sharing data and materials. NR 21 TC 17 Z9 19 U1 0 U2 4 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA SN 1932-6203 J9 PLOS ONE JI PLoS One PD APR 9 PY 2012 VL 7 IS 4 AR e33619 DI 10.1371/journal.pone.0033619 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 955JO UT WOS:000305014500013 PM 22496757 ER PT J AU Bennett, GG Warner, ET Glasgow, RE Askew, S Goldman, J Ritzwoller, DP Emmons, KM Rosner, BA Colditz, GA AF Bennett, Gary G. Warner, Erica T. Glasgow, Russell E. Askew, Sandy Goldman, Julie Ritzwoller, Debra P. Emmons, Karen M. Rosner, Bernard A. Colditz, Graham A. CA Be Fit Be Well Study Investigators TI Obesity Treatment for Socioeconomically Disadvantaged Patients in Primary Care Practice SO ARCHIVES OF INTERNAL MEDICINE LA English DT Article ID BODY-MASS INDEX; NUTRITION EXAMINATION SURVEY; WEIGHT-LOSS MAINTENANCE; BLOOD-PRESSURE; LIFE-STYLE; AFRICAN-AMERICAN; UNITED-STATES; CARDIOVASCULAR RISK; ETHNIC DISPARITIES; CANCER PREVENTION AB Background: Few evidence-based weight loss treatment options exist for medically vulnerable patients in the primary care setting. Methods: We conducted a 2-arm, 24-month randomized effectiveness trial in 3 Boston community health centers (from February 1, 2008, through May 2, 2011). Participants were 365 obese patients receiving hypertension treatment (71.2% black, 13.1% Hispanic, 68.5% female, and 32.9% with less than a high school educational level). We randomized participants to usual care or a behavioral intervention that promoted weight loss and hypertension self-management using eHealth components. The intervention included tailored behavior change goals, self-monitoring, and skills training, available via a website or interactive voice response; 18 telephone counseling calls; primary care provider endorsement; 12 optional group support sessions; and links with community resources. Results: At 24 months, weight change in the intervention group compared with that in the usual care group was -1.03 kg (95% CI, -2.03 to -0.03 kg). Twenty-four-month change in body mass index (calculated as weight in kilograms divided by height in meters squared) in the intervention group compared with that in the usual care group was -0.38 (95% CI, -0.75 to -0.004). Intervention participants had larger mean weight losses during the 24 months compared with that in the usual care group (area under the receiver operating characteristic curve, -1.07 kg; 95% CI, -1.94 to -0.22). Mean systolic blood pressure was not significantly lower in the intervention arm compared with the usual care arm. Conclusion: The intervention produced modest weight losses, improved blood pressure control, and slowed systolic blood pressure increases in this high-risk, socio-economically disadvantaged patient population. C1 [Bennett, Gary G.; Askew, Sandy] Duke Univ, Duke Obes Prevent Program, Durham, NC 27708 USA. [Bennett, Gary G.] Duke Univ, Dept Psychol & Neurosci, Durham, NC 27708 USA. [Bennett, Gary G.; Askew, Sandy] Duke Univ, Duke Global Hlth Inst, Durham, NC 27708 USA. [Warner, Erica T.; Colditz, Graham A.] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. [Bennett, Gary G.; Emmons, Karen M.] Harvard Univ, Sch Publ Hlth, Dept Soc, Boston, MA 02115 USA. [Bennett, Gary G.; Emmons, Karen M.] Harvard Univ, Sch Publ Hlth, Dept Human Dev, Boston, MA 02115 USA. [Bennett, Gary G.; Emmons, Karen M.] Harvard Univ, Sch Publ Hlth, Dept Hlth, Boston, MA 02115 USA. [Rosner, Bernard A.] Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA. [Rosner, Bernard A.] Harvard Univ, Sch Med, Dept Med, Boston, MA USA. [Bennett, Gary G.; Warner, Erica T.; Askew, Sandy; Goldman, Julie; Emmons, Karen M.] Dana Farber Canc Inst, Ctr Community Based Res, Div Populat Sci, Boston, MA 02115 USA. [Glasgow, Russell E.] NCI, Div Canc Control & Populat Sci, Bethesda, MD 20892 USA. [Ritzwoller, Debra P.] Kaiser Permanente, Inst Hlth Res, Denver, CO USA. [Colditz, Graham A.] Washington Univ, Sch Med, Div Publ Hlth Sci, Alvin J Siteman Canc Ctr,Dept Surg, St Louis, MO USA. RP Bennett, GG (reprint author), Duke Univ, Duke Obes Prevent Program, POB 90086, Durham, NC 27708 USA. EM gary.bennett@duke.edu RI Colditz, Graham/A-3963-2009 OI Colditz, Graham/0000-0002-7307-0291 FU National Heart, Lung, and Blood Institute [U01-HL087071]; National Cancer Institute [K22CA126992, K05CA124415-04] FX This work was supported in part by grant U01-HL087071 from the National Heart, Lung, and Blood Institute and grants K22CA126992 (Dr Bennett) and K05CA124415-04 (Dr Emmons) from the National Cancer Institute. NR 58 TC 67 Z9 68 U1 2 U2 28 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60654-0946 USA SN 0003-9926 J9 ARCH INTERN MED JI Arch. Intern. Med. PD APR 9 PY 2012 VL 172 IS 7 BP 565 EP 574 DI 10.1001/archinternmed.2012.1 PG 10 WC Medicine, General & Internal SC General & Internal Medicine GA 922NV UT WOS:000302555300006 PM 22412073 ER PT J AU Pilotto, A Panza, F Ferrucci, L AF Pilotto, Alberto Panza, Francesco Ferrucci, Luigi TI A Multidimensional Prognostic Index in Common Conditions Leading to Death in Older Patients SO ARCHIVES OF INTERNAL MEDICINE LA English DT Letter ID COMPREHENSIVE GERIATRIC ASSESSMENT; LONG-TERM MORTALITY C1 [Pilotto, Alberto] S Antonio Hosp, Geriatr Unit, Azienda ULSS Padova 16, I-35127 Padua, Italy. [Pilotto, Alberto; Panza, Francesco] IRCCS Casa Sollievo Sofferenza, Geriatr Unit, San Giovanni Rotondo, Italy. [Pilotto, Alberto; Panza, Francesco] IRCCS Casa Sollievo Sofferenza, Gerontol Geriatr Res Lab, San Giovanni Rotondo, Italy. [Ferrucci, Luigi] NIA, Clin Res Branch, Baltimore, MD 21224 USA. RP Pilotto, A (reprint author), S Antonio Hosp, Geriatr Unit, Azienda ULSS Padova 16, Via Facciolati 71, I-35127 Padua, Italy. EM alberto.pilotto@sanita.padova.it NR 5 TC 9 Z9 9 U1 1 U2 2 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60654-0946 USA SN 0003-9926 J9 ARCH INTERN MED JI Arch. Intern. Med. PD APR 9 PY 2012 VL 172 IS 7 BP 594 EP 594 PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA 922NV UT WOS:000302555300015 PM 22493470 ER PT J AU Okoye, AA Rohankhedkar, M Abana, C Pattenn, A Reyes, M Pexton, C Lum, R Sylwester, A Planer, SL Legasse, A Park, BS Piatak, M Lifson, JD Axthelm, MK Picker, LJ AF Okoye, Afam A. Rohankhedkar, Mukta Abana, Chike Pattenn, Audrie Reyes, Matthew Pexton, Christopher Lum, Richard Sylwester, Andrew Planer, Shannon L. Legasse, Alfred Park, Byung S. Piatak, Michael, Jr. Lifson, Jeffrey D. Axthelm, Michael K. Picker, Louis J. TI Naive T cells are dispensable for memory CD4(+) T cell homeostasis in progressive simian immunodeficiency virus infection SO JOURNAL OF EXPERIMENTAL MEDICINE LA English DT Article ID CD8(+) LYMPHOCYTE DEPLETION; RHESUS MACAQUES; SIV INFECTION; PATHOGENESIS; PROTECTION; EXPANSION; IMMUNITY; DECLINE; MONKEYS; DISEASE AB The development of AIDS in chronic HIV/simian immunodeficiency virus (SIV) infection has been closely linked to progressive failure of CD4(+) memory T cell (T-M) homeostasis. CD4(+) naive T cells (T-N) also decline in these infections, but their contribution to disease progression is less clear. We assessed the role of CD4(+) T-N in SIV pathogenesis using rhesus macaques (RMs) selectively and permanently depleted of CD4(+) T-N before SIV infection. CD4(+) T-N-depleted and CD4(+) T-N-repleted RMs were created by subjecting juvenile RMs to thymectomy versus sham surgery, respectively, followed by total CD4(+) T cell depletion and recovery from this depletion. Although thymectomized and sham-treated RMs manifested comparable CD4(+) T-M recovery, only sham-treated RMs reconstituted CD4(+) T-N. CD4(+) T-N-depleted RMs responded to SIVmac239 infection with markedly attenuated SIV-specific CD4(+) T cell responses, delayed SIVenv-specific Ab responses, and reduced SIV-specific CD8(+) T cell responses. However, CD4(+) T-N-depleted and -repleted groups showed similar levels of SIV replication. Moreover, CD4(+) T-N deficiency had no significant effect on CD4(+) T-M homeostasis (either on or off anti-retroviral therapy) or disease progression. These data demonstrate that the CD4(+) T-N compartment is dispensable for CD4+ T-M homeostasis in progressive SIV infection, and they confirm that CD4(+) T-M comprise a homeostatically independent compartment that is intrinsically capable of self-renewal. C1 [Okoye, Afam A.; Rohankhedkar, Mukta; Abana, Chike; Pattenn, Audrie; Reyes, Matthew; Pexton, Christopher; Lum, Richard; Sylwester, Andrew; Planer, Shannon L.; Legasse, Alfred; Axthelm, Michael K.; Picker, Louis J.] Oregon Hlth & Sci Univ, Oregon Natl Primate Res Ctr, Vaccine & Gene Therapy Inst, Dept Pathol, Beaverton, OR 97006 USA. [Okoye, Afam A.; Rohankhedkar, Mukta; Abana, Chike; Pattenn, Audrie; Reyes, Matthew; Pexton, Christopher; Lum, Richard; Sylwester, Andrew; Planer, Shannon L.; Legasse, Alfred; Axthelm, Michael K.; Picker, Louis J.] Oregon Hlth & Sci Univ, Oregon Natl Primate Res Ctr, Vaccine & Gene Therapy Inst, Dept Mol Microbiol & Immunol, Beaverton, OR 97006 USA. [Park, Byung S.] Oregon Hlth & Sci Univ, Dept Publ Hlth & Prevent Med, Div Biostat, Portland, OR 97239 USA. [Piatak, Michael, Jr.; Lifson, Jeffrey D.] NCI, AIDS Vaccine Program, SAIC Frederick Inc, Frederick, MD 21702 USA. RP Picker, LJ (reprint author), Oregon Hlth & Sci Univ, Oregon Natl Primate Res Ctr, Vaccine & Gene Therapy Inst, Dept Pathol, Beaverton, OR 97006 USA. EM pickerl@ohsu.edu OI /0000-0003-3516-7516 FU National Institutes of Health [R37-AI054292, P51-RR00163]; National Cancer Institute, National Institutes of Health [HHSN261200800001E] FX This work was supported by National Institutes of Health grants R37-AI054292 and P51-RR00163 and federal funds from the National Cancer Institute, National Institutes of Health, under Contract No. HHSN261200800001E. NR 32 TC 15 Z9 15 U1 0 U2 3 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 1114 FIRST AVE, 4TH FL, NEW YORK, NY 10021 USA SN 0022-1007 J9 J EXP MED JI J. Exp. Med. PD APR 9 PY 2012 VL 209 IS 4 BP 641 EP 651 DI 10.1084/jem.20112071 PG 11 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA 925SS UT WOS:000302782300001 PM 22451717 ER PT J AU Scheibye-Knudsen, M Ramamoorthy, M Sykora, P Maynard, S Lin, PC Minor, RK Wilson, DM Cooper, M Spencer, R de Cabo, R Croteau, DL Bohr, VA AF Scheibye-Knudsen, Morten Ramamoorthy, Mahesh Sykora, Peter Maynard, Scott Lin, Ping-Chang Minor, Robin K. Wilson, David M., III Cooper, Marcus Spencer, Richard de Cabo, Rafael Croteau, Deborah L. Bohr, Vilhelm A. TI Cockayne syndrome group B protein prevents the accumulation of damaged mitochondria by promoting mitochondrial autophagy SO JOURNAL OF EXPERIMENTAL MEDICINE LA English DT Article ID LIFE-SPAN EXTENSION; BASE EXCISION-REPAIR; NEURODEGENERATIVE DISEASES; CALORIE RESTRICTION; C-ELEGANS; DNA; CELLS; TRANSCRIPTION; MICE; DYSFUNCTION AB Cockayne syndrome (CS) is a devastating autosomal recessive disease characterized by neurodegeneration, cachexia, and accelerated aging. 80% of the cases are caused by mutations in the CS complementation group B (CSB) gene known to be involved in DNA repair and transcription. Recent evidence indicates that CSB is present in mitochondria, where it associates with mitochondrial DNA (mtDNA). We report an increase in metabolism in the CSBm/m mouse model and CSB-deficient cells. Mitochondrial content is increased in CSB-deficient cells, whereas autophagy is down-regulated, presumably as a result of defects in the recruitment of P62 and mitochondrial ubiquitination. CSB-deficient cells show increased free radical production and an accumulation of damaged mitochondria. Accordingly, treatment with the autophagic stimulators lithium chloride or rapamycin reverses the bioenergetic phenotype of CSB-deficient cells. Our data imply that CSB acts as an mtDNA damage sensor, inducing mitochondrial autophagy in response to stress, and that pharmacological modulators of autophagy are potential treatment options for this accelerated aging phenotype. C1 [Scheibye-Knudsen, Morten; Ramamoorthy, Mahesh; Sykora, Peter; Wilson, David M., III; Croteau, Deborah L.; Bohr, Vilhelm A.] NIA, Lab Mol Gerontol, NIH, Baltimore, MD 21224 USA. [Maynard, Scott; Lin, Ping-Chang; Spencer, Richard] NIA, Magnet Resonance Imaging & Spect Sect, NIH, Baltimore, MD 21224 USA. [Minor, Robin K.; de Cabo, Rafael] NIA, Lab Expt Gerontol, NIH, Baltimore, MD 21224 USA. [Bohr, Vilhelm A.] Univ Copenhagen, Ctr Hlth Aging, Inst Cellular & Mol Med, DK-1165 Copenhagen, Denmark. [Cooper, Marcus] Univ Massachusetts, Sch Med, Div Cardiovasc Med, Worcester, MA 01655 USA. RP Bohr, VA (reprint author), NIA, Lab Mol Gerontol, NIH, Baltimore, MD 21224 USA. EM vbohr@nih.gov RI de Cabo, Rafael/J-5230-2016; OI de Cabo, Rafael/0000-0002-3354-2442; Maynard, Scott/0000-0001-5625-936X; Lin, Ping-Chang/0000-0003-0918-4072; Scheibye-Knudsen, Morten/0000-0002-6637-1280; Ramamoorthy, Mahesh/0000-0002-2359-5647; , rafael/0000-0003-2830-5693 FU NIH, National Institute on Aging FX This research was supported entirely by the Intramural Research Program of the NIH, National Institute on Aging. NR 58 TC 69 Z9 69 U1 1 U2 8 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 APR 9 PY 2012 VL 209 IS 4 BP 855 EP 869 DI 10.1084/jem.20111721 PG 15 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA 925SS UT WOS:000302782300016 PM 22473955 ER PT J AU Lloyd-Sherlock, P McKee, M Ebrahim, S Gorman, M Greengross, S Prince, M Pruchno, R Gutman, G Kirkwood, T O'Neill, D Ferrucci, L Kritchevsky, SB Vellas, B AF Lloyd-Sherlock, Peter McKee, Martin Ebrahim, Shah Gorman, Mark Greengross, Sally Prince, Martin Pruchno, Rachel Gutman, Gloria Kirkwood, Tom O'Neill, Desmond Ferrucci, Luigi Kritchevsky, Stephen B. Vellas, Bruno TI Population ageing and health SO LANCET LA English DT Letter C1 [Lloyd-Sherlock, Peter] Univ E Anglia, Sch Dev Studies, Norwich NR4 7TJ, Norfolk, England. [McKee, Martin] London Sch Hyg & Trop Med, European Ctr Hlth Soc Transit, London WC1, England. [Ebrahim, Shah] Publ Hlth Fdn India, S Asia Network Chron Dis, New Delhi, India. [Gorman, Mark] HelpAge Int, London, England. [Greengross, Sally] Int Longev Ctr UK, London, England. [Prince, Martin] Kings Coll London, Inst Psychiat, London WC2R 2LS, England. [Pruchno, Rachel] New Jersey Inst Successful Aging, Stratford, NJ USA. [Gutman, Gloria] Int Network Prevent Elder Abuse, Vancouver, BC, Canada. [Kirkwood, Tom] Newcastle Univ, Newcastle Upon Tyne NE1 7RU, Tyne & Wear, England. [O'Neill, Desmond] European Union Geriatr Med Soc, Brussels, Belgium. [Ferrucci, Luigi] NIA, Bethesda, MD 20892 USA. [Kritchevsky, Stephen B.] Sticht Ctr Aging, Winston Salem, NC USA. [Vellas, Bruno] Int Assoc Gerontol & Geriatr, Liege, Belgium. RP Lloyd-Sherlock, P (reprint author), Univ E Anglia, Sch Dev Studies, Norwich NR4 7TJ, Norfolk, England. EM p.lloyd-sherlock@uea.ac.uk RI Prince, Martin/A-9170-2010; OI Prince, Martin/0000-0003-1379-7146; Gutman, Gloria/0000-0001-8810-2287; Pruchno, Rachel/0000-0001-7440-4495; Kritchevsky, Stephen/0000-0003-3336-6781; O'Neill, Desmond/0000-0002-5542-9897 FU Wellcome Trust [084674] NR 3 TC 35 Z9 36 U1 1 U2 13 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0140-6736 J9 LANCET JI Lancet PD APR 7 PY 2012 VL 379 IS 9823 BP 1295 EP 1296 DI 10.1016/S0140-6736(12)60519-4 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA 922FB UT WOS:000302531100015 PM 22480756 ER PT J AU Zhou, XL Yang, XY Popescu, NC AF Zhou, Xiaoling Yang, Xu-Yu Popescu, Nicholas C. TI Preclinical evaluation of combined antineoplastic effect of DLC1 tumor suppressor protein and suberoylanilide hydroxamic acid on prostate cancer cells SO BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS LA English DT Article DE DLC1; Tumor suppressor gene; SAHA; Apoptosis; RhoA activity; Inhibition prostate tumor growth in vivo ID HISTONE-DEACETYLASE INHIBITORS; RHO-GTPASES; GENE; THERAPY; TRANSFORMATION; PERSPECTIVES; METASTASIS; CARCINOMA; MIGRATION; GROWTH AB Deleted in liver cancer (DLC1), a tumor suppressor gene in multiple cancers, is recurrently down regulated or inactivated by epigenetic mechanisms in primary prostate carcinomas (PCAs). In this study the methylation and acetylation profile of the DLC1 promoter region was examined in three PCA cell lines with low or undetectable DLC1 expression: LNCaP, its derivative C4-2B-2, and 22Rv1. Two histone deacetylase inhibitors (HDAC), suberoylanilide hydroxamic acid (SAHA) and trichostatin A (TSA) induced histone acetylation of the DLC1 promoter in all three lines. DLC1 promoter methylation and deacetylation were detected in LNCaP and C4-2B-2 cells while in 22Rv1 cells DLC1 is silenced by deacetylation. Treatment with SAHA or TSA efficiently increased DLC1 expression in all lines, particularly in 22Rv1 cells, and activated the DLC1 promoter through the same Spl sites. The 22Rv1 cell line was selected to evaluate the efficacy of combined DLC1 transduction and SAHA treatment on tumor growth in athymic mice. Individually. DLC1 transduction and SAHA exposure reduced the tumor size by 75-80% compared to controls and in combination almost completely inhibited tumor growth. The antitumor effect was associated with the induction of apoptosis and inhibition of RhoA activity. SAHA alone significantly reduced RhoA activity, showing that this RhoGTPase is a target for SAHA. These results, obtained with a reliable preclinical in vivo test, predict that combined therapeutic agents targeting the pathways governing DLC1 function and HDAC inhibitors may be beneficial in management of prostate cancer. (C) 2012 Elsevier Inc. All rights reserved. C1 [Zhou, Xiaoling; Yang, Xu-Yu; Popescu, Nicholas C.] NCI, Expt Carcinogenesis Lab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. RP Popescu, NC (reprint author), NCI, Expt Carcinogenesis Lab, Ctr Canc Res, NIH, 37 Convent Dr,MSC 4262, Bethesda, MD 20892 USA. EM popescun@mail.nih.gov RI yang, xuyu/D-1414-2012 FU National Cancer Institute, NIH FX This work was supported by the Intramural Research Program of the National Cancer Institute, NIH. NR 26 TC 5 Z9 5 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 0006-291X J9 BIOCHEM BIOPH RES CO JI Biochem. Biophys. Res. Commun. PD APR 6 PY 2012 VL 420 IS 2 BP 325 EP 330 DI 10.1016/j.bbrc.2012.02.158 PG 6 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 969FW UT WOS:000306042100020 PM 22425986 ER PT J AU Teijido, O Ujwal, R Hillerdal, CO Kullman, L Rostovtseva, TK Abramson, J AF Teijido, Oscar Ujwal, Rachna Hillerdal, Carl-Olof Kullman, Lisen Rostovtseva, Tatiana K. Abramson, Jeff TI Reply to Thinnes: To Include Plasmalemmal VDAC/Porin Pays SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Letter ID CHANNEL; VDAC C1 [Teijido, Oscar; Rostovtseva, Tatiana K.] Eunice Kennedy Shriver NICHD, Program Phys Biol, NIH, Bethesda, MD 20892 USA. [Ujwal, Rachna; Abramson, Jeff] Univ Calif Los Angeles, Dept Physiol, David Geffen Sch Med, Los Angeles, CA 90095 USA. [Hillerdal, Carl-Olof; Kullman, Lisen] Uppsala Univ, Dept Med Cell Biol, S-75123 Uppsala, Sweden. RP Teijido, O (reprint author), Eunice Kennedy Shriver NICHD, Program Phys Biol, NIH, Bethesda, MD 20892 USA. EM jabramson@mednet.ucla.edu NR 6 TC 0 Z9 0 U1 0 U2 3 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD APR 6 PY 2012 VL 287 IS 15 BP 12156 EP 12156 DI 10.1074/jbc.N111.314229 PG 1 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 925SR UT WOS:000302782200055 ER PT J AU Murase, S McKay, RD AF Murase, Sachiko McKay, Ronald D. TI Matrix Metalloproteinase-9 Regulates Survival of Neurons in Newborn Hippocampus SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID OCCURRING CELL-DEATH; MATRIX METALLOPROTEINASE-3; ALZHEIMERS-DISEASE; MOUSE HIPPOCAMPUS; LAMININ; EXPRESSION; RAT; SPECIFICITY; ACTIVATION; INTEGRINS AB The number of neurons in the adult rodent brain is strongly influenced by events in early postnatal life that eliminate approximately half of the neurons. Recently, we reported that neurotrophins induced survival of neonatal rat hippocampal neurons by promoting neural activity and activation of the Ser/Thr kinase, Akt. The survival of neurons also depended on integrin signaling, but a role for the extracellular matrix (ECM) in this mechanism was yet to be explored. Here, we show that levels of the matrix metalloproteinase-9 (MMP9) decrease, and the level of the ECM protein laminin increases in rat hippocampus during the period of neuronal death. Hippocampi from MMP9 null mice showed higher levels of laminin expression than wild type at P1 and no further increase at P10. In vitro, the matrix metalloproteinase inhibitor FN-439 promoted survival of neurons in a laminin-integrin beta 1-dependent manner. Blocking laminin signaling attenuated activation of Akt by depolarization. In vivo, injecting FN-439 into the neonatal hippocampus increased the level of laminin and promoted neuronal survival through an integrin-dependent mechanism. These results show signals from the ECM are not simply permissive but rather actively regulated, and they interact with neuronal activity to control the number of hippocampal neurons. This work is the first to report a role for MMP9 in regulating neuronal survival through the developmental process that establishes the functional brain. C1 [Murase, Sachiko; McKay, Ronald D.] NINDS, Mol Biol Lab, NIH, Bethesda, MD 20892 USA. [McKay, Ronald D.] Lieber Inst Brain Dev, Baltimore, MD 21205 USA. RP Murase, S (reprint author), NINDS, Mol Biol Lab, NIH, 35 Lincoln Dr, Bethesda, MD 20892 USA. EM sachikom@ninds.nih.gov FU National Institutes of Health from NINDS FX This work was supported by a National Institutes of Health grant from the Intramural Research Program, NINDS. NR 39 TC 15 Z9 15 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 APR 6 PY 2012 VL 287 IS 15 BP 12184 EP 12194 DI 10.1074/jbc.M111.297671 PG 11 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 925SR UT WOS:000302782200060 PM 22351756 ER PT J AU Duverger, O Zah, A Isaac, J Sun, HW Bartels, AK Lian, JB Berdal, A Hwang, J Morasso, MI AF Duverger, Olivier Zah, Angela Isaac, Juliane Sun, Hong-Wei Bartels, Anne K. Lian, Jane B. Berdal, Ariane Hwang, Joonsung Morasso, Maria I. TI Neural Crest Deletion of Dlx3 Leads to Major Dentin Defects through Down-regulation of Dspp SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID CHIP-SEQ DATA; TRICHODENTOOSSEOUS SYNDROME; SIALOPHOSPHOPROTEIN EXPRESSION; TOOTH DEVELOPMENT; MURINE DENTITION; GENE-EXPRESSION; HOMEOBOX GENES; ENAMEL DEFECTS; DIFFERENTIATION; MUTATION AB During development, Dlx3 is expressed in ectodermal appendages such as hair and teeth. Thus far, the evidence that Dlx3 plays a crucial role in tooth development comes from reports showing that autosomal dominant mutations in DLX3 result in severe enamel and dentin defects leading to abscesses and infections. However, the normal function of DLX3 in odontogenesis remains unknown. Here, we use a mouse model to demonstrate that the absence of Dlx3 in the neural crest results in major impairment of odontoblast differentiation and dentin production. Mutant mice develop brittle teeth with hypoplastic dentin and molars with an enlarged pulp chamber and underdeveloped roots. Using this mouse model, we found that dentin sialophosphoprotein (Dspp), a major component of the dentin matrix, is strongly down-regulated in odontoblasts lacking Dlx3. Using ChIP-seq, we further demonstrate the direct binding of Dlx3 to the Dspp promoter in vivo. Luciferase reporter assays determined that Dlx3 positively regulates Dspp expression. This establishes a regulatory pathway where the transcription factor Dlx3 is essential in dentin formation by directly regulating a crucial matrix protein. C1 [Duverger, Olivier; Zah, Angela; Isaac, Juliane; Bartels, Anne K.; Hwang, Joonsung; Morasso, Maria I.] NIAMS, Dev Skin Biol Sect, NIH, Bethesda, MD 20892 USA. [Sun, Hong-Wei] NIAMS, Biodata Min & Discovery Sect, NIH, Bethesda, MD 20892 USA. [Lian, Jane B.] Univ Massachusetts, Dept Cell Biol, Sch Med, Worcester, MA 01655 USA. [Lian, Jane B.] Univ Massachusetts, Dept Orthoped Surg, Sch Med, Worcester, MA 01655 USA. [Berdal, Ariane] Univ Paris 05, INSERM, UMRS 872, Team 5, F-75006 Paris, France. [Berdal, Ariane] Univ Paris 06, INSERM, UMRS 872, Team 5, F-75006 Paris, France. RP Morasso, MI (reprint author), NIAMS, Dev Skin Biol Sect, NIH, 50 South Dr,Room 1523, Bethesda, MD 20892 USA. EM morasso@nih.gov FU NIAMS, National Institutes of Health; National Institutes of Health [R37 DE012528] FX This work was supported by the Intramural Research Program of the NIAMS, National Institutes of Health.; Supported by National Institutes of Health Grant R37 DE012528. NR 51 TC 22 Z9 23 U1 0 U2 9 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 EI 1083-351X J9 J BIOL CHEM JI J. Biol. Chem. PD APR 6 PY 2012 VL 287 IS 15 BP 12230 EP 12240 DI 10.1074/jbc.M111.326900 PG 11 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 925SR UT WOS:000302782200064 PM 22351765 ER PT J AU Lee, MS Bonner, JR Bernard, DJ Sanchez, EL Sause, ET Prentice, RR Burgess, SM Brody, LC AF Lee, Marina S. Bonner, Jenna R. Bernard, David J. Sanchez, Erica L. Sause, Eric T. Prentice, R. Reid Burgess, Shawn M. Brody, Lawrence C. TI Disruption of the folate pathway in zebrafish causes developmental defects SO BMC DEVELOPMENTAL BIOLOGY LA English DT Article ID DEPENDENT METHYLENETETRAHYDROFOLATE DEHYDROGENASE; METHIONINE ADENOSYLTRANSFERASE; RISK-FACTOR; REDUCTASE; GENE; CANCER; MICE; IDENTIFICATION; MITOCHONDRIA; METHOTREXATE AB Background: Folic acid supplementation reduces the risk of neural tube defects and congenital heart defects. The biological mechanisms through which folate prevents birth defects are not well understood. We explore the use of zebrafish as a model system to investigate the role of folate metabolism during development. Results: We first identified zebrafish orthologs of 12 human folate metabolic genes. RT-PCR and in situ analysis indicated maternal transcripts supply the embryo with mRNA so that the embryo has an intact folate pathway. To perturb folate metabolism we exposed zebrafish embryos to methotrexate (MTX), a potent inhibitor of dihydrofolate reductase (Dhfr) an essential enzyme in the folate metabolic pathway. Embryos exposed to high doses of MTX exhibited developmental arrest prior to early segmentation. Lower doses of MTX resulted in embryos with a shortened anterior-posterior axis and cardiac defects: linear heart tubes or incomplete cardiac looping. Inhibition of dhfr mRNA with antisense morpholino oligonucleotides resulted in embryonic lethality. One function of the folate pathway is to provide essential one-carbon units for dTMP synthesis, a rate-limiting step of DNA synthesis. After 24 hours of exposure to high levels of MTX, mutant embryos continue to incorporate the thymidine analog BrdU. However, additional experiments indicate that these embryos have fewer mitotic cells, as assayed with phospho-histone H3 antibodies, and that treated embryos have perturbed cell cycles. Conclusions: Our studies demonstrate that human and zebrafish utilize similar one-carbon pathways. Our data indicate that folate metabolism is essential for early zebrafish development. Zebrafish studies of the folate pathway and its deficiencies could provide insight into the underlying etiology of human birth defects and the natural role of folate in development. C1 [Lee, Marina S.; Bonner, Jenna R.; Bernard, David J.; Sanchez, Erica L.; Sause, Eric T.; Prentice, R. Reid; Burgess, Shawn M.; Brody, Lawrence C.] NHGRI, NIH, Bethesda, MD 20892 USA. RP Brody, LC (reprint author), NHGRI, NIH, Bethesda, MD 20892 USA. EM lbrody@mail.nih.gov OI Burgess, Shawn/0000-0003-1147-0596 FU Intramural Research Program of the National Human Genome Research Institute, National Institutes of Health FX We thank Stacie Anderson for help with FACS analysis, Darryl Leja for help with figures, Settara Chandrasekharappa for equipment, Amy Singer of the ZFIN Nomenclature Committee for naming help, and Charles River Aquatic Staff for fish care. This research was supported by the Intramural Research Program of the National Human Genome Research Institute, National Institutes of Health (S.M.B, L.C.B). NR 40 TC 11 Z9 13 U1 0 U2 22 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1471-213X J9 BMC DEV BIOL JI BMC Dev. Biol. PD APR 5 PY 2012 VL 12 AR 12 DI 10.1186/1471-213X-12-12 PG 11 WC Developmental Biology SC Developmental Biology GA 982TH UT WOS:000307067800001 PM 22480165 ER PT J AU Dakshinamoorthy, G Samykutty, AK Munirathinam, G Shinde, GB Nutman, T Reddy, MV Kalyanasundaram, R AF Dakshinamoorthy, Gajalakshmi Samykutty, Abhilash Kumble Munirathinam, Gnanasekar Shinde, Gangadhar Bhaurao Nutman, Thomas Reddy, Maryada Venkatarami Kalyanasundaram, Ramaswamy TI Biochemical Characterization and Evaluation of a Brugia malayi Small Heat Shock Protein as a Vaccine against Lymphatic Filariasis SO PLOS ONE LA English DT Article ID ALPHA-CRYSTALLIN DOMAIN; WUCHERERIA-BANCROFTI; PROTECTIVE IMMUNITY; DNA VACCINATION; ANTIBODY-RESPONSES; INFECTIVE LARVAE; ANTIGEN; TUBERCULOSIS; IMMUNOGENICITY; MICE AB Filarial nematodes enjoy one of the longest life spans of any human pathogen due to effective immune evasion strategies developed by the parasite. Among the various immune evasion strategies exhibited by the parasite, Interleukin 10 (IL-10) productions and IL-10 mediated immune suppression has significant negative impact on the host immune system. Recently, we identified a small heat shock protein expressed by Brugia malayi (BmHsp12.6) that can bind to soluble human IL-10 receptor alpha (IL-10R) and activate IL-10 mediated effects in cell lines. In this study we show that the IL-10R binding region of BmHsp12.6 is localized to its N-terminal region. This region has significant sequence similarity to the receptor binding region of human IL-10. In vitro studies confirm that the N-terminal region of BmHsp12.6 (N-BmHsp12.6) has IL-10 like activity and the region containing the alpha crystalline domain and C-terminus of BmHsp12.6 (BmHsp12.6ac) has no IL-10 like activity. However, BmHsp12.6ac contains B cell, T cell and CTL epitopes. Members of the sHSP families are excellent vaccine candidates. Evaluation of sera samples from putatively immune endemic normal (EN) subjects showed IgG1 and IgG3 antibodies against BmHsp12.6ac and these antibodies were involved in the ADCC mediated protection. Subsequent vaccination trials with BmHsp12.6ac in a mouse model using a heterologous prime boost approach showed that 83% protection can be achieved against B. malayi L3 challenge. Results presented in this study thus show that the N-BmHsp12.6 subunit of BmHsp12.6 has immunoregulatory function, whereas, the BmHsp12.6ac subunit of BmHsp12.6 has significant vaccine potential. C1 [Dakshinamoorthy, Gajalakshmi; Samykutty, Abhilash Kumble; Munirathinam, Gnanasekar; Kalyanasundaram, Ramaswamy] Univ Illinois, Coll Med Rockford, Dept Biomed Sci, Rockford, IL USA. [Samykutty, Abhilash Kumble; Reddy, Maryada Venkatarami] Mahatma Gandhi Inst Med Sci, Dept Biochem, Sevagram, Maharashtra, India. [Shinde, Gangadhar Bhaurao] Rashtrasant Tukadoji Maharaj Nagpur Univ, Dept Biochem, Nagpur, Maharashtra, India. [Nutman, Thomas] NIH, Helminth Immunol Sect, Bethesda, MD 20892 USA. RP Dakshinamoorthy, G (reprint author), Univ Illinois, Coll Med Rockford, Dept Biomed Sci, Rockford, IL USA. EM ramswamy@uic.edu FU NIH [AI064745]; Department of Biotechnology, Ministry of Science and Technology, New Delhi [BT/INF/22/1/2007] FX This study was funded by an NIH RO1 grant (AI064745). Additional funding was received from the Department of Biotechnology, Ministry of Science and Technology, New Delhi (BT/INF/22/1/2007). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 61 TC 22 Z9 22 U1 2 U2 10 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA SN 1932-6203 J9 PLOS ONE JI PLoS One PD APR 5 PY 2012 VL 7 IS 4 AR e34077 DI 10.1371/journal.pone.0034077 PG 15 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 955IH UT WOS:000305010500004 PM 22496777 ER PT J AU Dunleavy, K Wilson, WH AF Dunleavy, Kieron Wilson, Wyndham H. TI How I treat HIV-associated lymphoma SO BLOOD LA English DT Review ID HUMAN-IMMUNODEFICIENCY-VIRUS; B-CELL LYMPHOMA; NON-HODGKINS-LYMPHOMA; PRIMARY EFFUSION LYMPHOMA; ACTIVE ANTIRETROVIRAL THERAPY; AIDS-RELATED LYMPHOMA; NERVOUS-SYSTEM LYMPHOMA; GENE-EXPRESSION PROFILE; NF-KAPPA-B; BURKITTS-LYMPHOMA AB Over the past 10 years, significant progress has been made in understanding HIV-associated lymphomas and improving the prognosis of these diseases. With the advent of combination antiretroviral therapy and the development of novel therapeutic strategies, most patients with HIV-associated lymphomas are cured. The outcome for the majority of patients with HIV-associated diffuse large B-cell lymphoma and Burkitt lymphoma in particular, is excellent, with recent studies supporting the role of rituximab in these diseases. Indeed, in the combination antiretroviral therapy era, the curability of many patients with HIV-associated lymphoma is similar to their HIV-negative counterparts. New treatment frontiers need to focus on improving the outcome for patients with advanced immune suppression and for those with adverse tumor biology, such as the activated B-cell type of diffuse large B-cell lymphoma and the virally driven lymphomas. Future clinical trials need to investigate novel targeted agents alone and in combination with chemotherapy. (Blood. 2012; 119(14): 3245-3255) C1 [Dunleavy, Kieron] NCI, Metab Branch, Ctr Canc Res, Bethesda, MD 20892 USA. RP Dunleavy, K (reprint author), NCI, Metab Branch, Ctr Canc Res, Bldg 10,Rm 4N-115,9000 Rockville Pike, Bethesda, MD 20892 USA. EM dunleavk@mail.nih.gov FU National Cancer Institute of the National Institutes of Health FX This work was supported by the Intramural Research Program of the National Cancer Institute of the National Institutes of Health. NR 89 TC 51 Z9 55 U1 0 U2 9 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 2021 L ST NW, SUITE 900, WASHINGTON, DC 20036 USA SN 0006-4971 EI 1528-0020 J9 BLOOD JI Blood PD APR 5 PY 2012 VL 119 IS 14 BP 3245 EP 3255 DI 10.1182/blood-2011-08-373738 PG 11 WC Hematology SC Hematology GA 925PL UT WOS:000302773200014 PM 22337719 ER PT J AU Xi, LQ Arons, E Navarro, W Calvo, KR Stetler-Stevenson, M Raffeld, M Kreitman, RJ AF Xi, Liqiang Arons, Evgeny Navarro, Winnifred Calvo, Katherine R. Stetler-Stevenson, Maryalice Raffeld, Mark Kreitman, Robert J. TI Both variant and IGHV4-34-expressing hairy cell leukemia lack the BRAF V600E mutation SO BLOOD LA English DT Article ID DIAGNOSIS; CLADRIBINE; DISEASE; CANCER AB Recently, the BRAF V600E mutation was reported in all cases of hairy cell leukemia (HCL) but not in other peripheral B-cell neoplasms. We wished to confirm these results and assess BRAF status in well-characterized cases of HCL associated with poor prognosis, including the immunophenotypically defined HCL variant (HCLv) and HCL expressing the IGHV4-34 immunoglobulin rearrangement. Fifty-three classic HCL (HCLc) and 16 HCLv cases were analyzed for BRAF, including 5 HCLc and 8 HCLv expressing IGHV4-34. BRAF was mutated in 42 (79%) HCLc, but wild-type in 11 (21%) HCLc and 16 (100%) HCLv. All 13 IGHV4-34(+) HCLs were wild-type. IGHV gene usage in the 11 HCLc BRAF wild-type cases included 5 IGHV4-34, 5 other, and 1 unknown. Our results suggest that HCLv and IGHV4-34(+) HCLs have a different pathogenesis than HCLc and that a significant minority of other HCLc are also wild-type for BRAF V600. (Blood. 2012; 119(14): 3330-3332) C1 [Arons, Evgeny; Kreitman, Robert J.] NCI, Mol Biol Lab, NIH, Bethesda, MD 20892 USA. [Xi, Liqiang; Navarro, Winnifred; Stetler-Stevenson, Maryalice; Raffeld, Mark] NCI, Pathol Lab, NIH, Bethesda, MD 20892 USA. [Calvo, Katherine R.] NIH, Dept Lab Med, Ctr Clin, Bethesda, MD 20892 USA. RP Kreitman, RJ (reprint author), NCI, Mol Biol Lab, NIH, 37-5124b,37 Convent Dr,MSC 4255, Bethesda, MD 20892 USA. EM kreitmar@mail.nih.gov RI Calvo, Katherine/A-8109-2009; OI Calvo, Katherine/0000-0002-0771-4191 FU National Cancer Institute, National Institutes of Health FX This work was supported by the intramural program of the National Cancer Institute, National Institutes of Health. NR 24 TC 82 Z9 85 U1 1 U2 4 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD APR 5 PY 2012 VL 119 IS 14 BP 3330 EP 3332 DI 10.1182/blood-2011-09-379339 PG 3 WC Hematology SC Hematology GA 925PL UT WOS:000302773200024 PM 22210875 ER PT J AU Borotikar, BS Sipprell, WH Wible, EE Sheehan, FT AF Borotikar, Bhushan S. Sipprell, William H., III Wible, Emily E. Sheehan, Frances T. TI A methodology to accurately quantify patellofemoral cartilage contact kinematics by combining 3D image shape registration and cine-PC MRI velocity data SO JOURNAL OF BIOMECHANICS LA English DT Article DE Knee; MRI; Dynamic; Femur; Patella; Contact kinematics ID IN-VIVO; TIBIOFEMORAL KINEMATICS; ARTICULAR-CARTILAGE; PATELLAR TRACKING; WEIGHT-BEARING; PAIN; JOINT; OSTEOARTHRITIS; PROGRESSION AB Patellofemoral osteoarthritis and its potential precursor patellofemoral pain syndrome (PFPS) are common, costly, and debilitating diseases. PFPS has been shown to be associated with altered patellofemoral joint mechanics; however, an actual variation in joint contact stresses has not been established due to challenges in accurately quantifying in vivo contact kinematics (area and location). This study developed and validated a method for tracking dynamic, in vivo cartilage contact kinematics by combining three magnetic resonance imaging (MRI) techniques, cine-phase contrast (CPC), multi-plane cine (MPC), and 3D high-resolution static imaging. CPC and MPC data were acquired from 12 healthy volunteers while they actively extended/flexed their knee within the MRI scanner. Since no gold standard exists for the quantification of in vivo dynamic cartilage contact kinematics, the accuracy of tracking a single point (patellar origin relative to the femur) represented the accuracy of tracking the kinematics of an entire surface. The accuracy was determined by the average absolute error between the PF kinematics derived through registration of MPC images to a static model and those derived through integration of the CPC velocity data. The accuracy ranged from 0.47 mm to 0.77 mm for the patella and femur and from 0.68 mm to 0.86 mm for the patellofemoral joint. For purely quantifying joint kinematics, CPC remains an analytically simpler and more accurate (accuracy <0.33 mm) technique. However, for application requiring the tracking of an entire surface, such as quantifying cartilage contact kinematics, this combined imaging approach produces accurate results with minimal operator intervention. Published by Elsevier Ltd. C1 [Borotikar, Bhushan S.; Wible, Emily E.; Sheehan, Frances T.] NIH, Dept Rehabil Med, Bethesda, MD 20892 USA. [Sipprell, William H., III] SUNY Buffalo, Sch Med & Biomed Sci, Buffalo, NY 14260 USA. RP Sheehan, FT (reprint author), NIH, Dept Rehabil Med, Bldg 10,CRC RM 1-1469,10 Ctr Dr,MSC 1604, Bethesda, MD 20892 USA. EM fsheehan@cc.nih.gov RI sheehan, frances/B-6962-2009 FU NIH at the Clinical Center; Diagnostic Radiology Department at the National Institutes of Health FX This research was supported in its entirety by the Intramural Research Program of the NIH at the Clinical Center at the NIH. The authors wish to thank Sara Sadeghi, Bonnie Damaska, and the Diagnostic Radiology Department at the National Institutes of Health for their support and research time. NR 28 TC 11 Z9 12 U1 0 U2 7 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0021-9290 J9 J BIOMECH JI J. Biomech. PD APR 5 PY 2012 VL 45 IS 6 BP 1117 EP 1122 DI 10.1016/j.jbiomech.2011.12.025 PG 6 WC Biophysics; Engineering, Biomedical SC Biophysics; Engineering GA 928KC UT WOS:000302980600033 PM 22284428 ER PT J AU Raghunathan, M Zubovski, Y Venable, RM Pastor, RW Nagle, JF Tristram-Nagle, S AF Raghunathan, Mohit Zubovski, Yuriy Venable, Richard M. Pastor, Richard W. Nagle, John F. Tristram-Nagle, Stephanie TI Structure and Elasticity of Lipid Membranes with Genistein and Daidzein Bioflavinoids Using X-ray Scattering and MD Simulations SO JOURNAL OF PHYSICAL CHEMISTRY B LA English DT Article ID ION-CHANNEL FUNCTION; BILAYER ELASTICITY; ESTROGEN-RECEPTOR; PROTEIN FUNCTION; GRAMICIDIN; BINDING; PHASE; BETA; PHYTOESTROGENS; ISOFLAVONES AB This work reports the effects of the bioflavinoids genistein and daidzein on lipid bilayers as determined by volume measurements, X-ray scattering, and molecular dynamics simulations. The experimental and simulated total molecular volumes were found to be in outstanding agreement with each other before the addition of genistein and daidzein and also after their addition. Both bioflavinoids inserted into the hydrocarbon region of both DOPC and diphytanoylPC near the carbonyls of the lipids and both decreased the bilayer thicknesses. The long axes of both bioflavinoids were oriented nearly parallel to the plane of the bilayer with their carbonyl groups preferentially pointed toward the proximal surface. A difference is that daidzein had a solubility limit of similar to 0.14 mol fraction in DOPC (similar to 0.12 mol fraction in diphytanoyIPC), whereas genistein was soluble at least to 0.20 mol fraction in both lipid membranes. Measurements of bending modulus K-C and simulation results for area compressibility modulus K-A indicate that both bioflavinoids soften bilayers. C1 [Raghunathan, Mohit; Zubovski, Yuriy; Nagle, John F.; Tristram-Nagle, Stephanie] Carnegie Mellon Univ, Dept Phys, Biol Phys Grp, Pittsburgh, PA 15213 USA. [Venable, Richard M.; Pastor, Richard W.] NHLBI, Lab Computat Biol, Rockville, MD 20852 USA. RP Tristram-Nagle, S (reprint author), Carnegie Mellon Univ, Dept Phys, Biol Phys Grp, 5000 Forbes Ave, Pittsburgh, PA 15213 USA. EM stn@cmu.edu RI Tristram-Nagle, Prof. Stephanie/N-7811-2014; Nagle, John/B-1917-2015 OI Tristram-Nagle, Prof. Stephanie/0000-0003-2271-7056; Nagle, John/0000-0002-9844-5934 FU NIGMS/NIH [GM 44976]; Howard Hughes Medical Institute; Charles E. Kaufman Foundation; NIH, National Heart, Lung and Blood Institute; National Science Foundation; National Institutes of Health/National Institute of General Medical Sciences under National Science Foundation [DMR-0225180] FX This research was supported in part by Grant No. GM 44976 from NIGMS/NIH (S.T.-N., J.N.), the Howard Hughes Medical Institute (M.R., Y.Z.), and the Charles E. Kaufman Foundation (S.T.-N.). It was supported in part (R.V., R.P.) by the Intramural Research Program of the NIH, National Heart, Lung and Blood Institute and utilized the high-performance computational capabilities at the National Institutes of Health, Bethesda, MD (NHLBI LoBoS cluster). X-ray scattering data were taken at the Cornell High Energy Synchrotron Source (CHESS), which is supported by the National Science Foundation and the National Institutes of Health/National Institute of General Medical Sciences under National Science Foundation Award DMR-0225180. We especially thank Dr. Arthur Woll for obtaining our beam and for general support during our data collection at the G1 station. We thank Dr. Jianjun Pan for help with sample preparation and X-ray data collection at CHESS, Prof. Olaf Andersen for helpful discussions, and especially Dr. Gilman Toombes for very insightful criticism of a first draft. NR 44 TC 32 Z9 33 U1 2 U2 15 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 1520-6106 J9 J PHYS CHEM B JI J. Phys. Chem. B PD APR 5 PY 2012 VL 116 IS 13 BP 3918 EP 3927 DI 10.1021/jp211904j PG 10 WC Chemistry, Physical SC Chemistry GA 919OG UT WOS:000302337000002 PM 22324769 ER PT J AU Hakim, O Resch, W Yamane, A Klein, I Kieffer-Kwon, KR Jankovic, M Oliveira, T Bothmer, A Voss, TC Ansarah-Sobrinho, C Mathe, E Liang, GQ Cobell, J Nakahashi, H Robbiani, DF Nussenzweig, A Hager, GL Nussenzweig, MC Casellas, R AF Hakim, Ofir Resch, Wolfgang Yamane, Arito Klein, Isaac Kieffer-Kwon, Kyong-Rim Jankovic, Mila Oliveira, Thiago Bothmer, Anne Voss, Ty C. Ansarah-Sobrinho, Camilo Mathe, Ewy Liang, Genqing Cobell, Jesse Nakahashi, Hirotaka Robbiani, Davide F. Nussenzweig, Andre Hager, Gordon L. Nussenzweig, Michel C. Casellas, Rafael TI DNA damage defines sites of recurrent chromosomal translocations in B lymphocytes SO NATURE LA English DT Article ID CLASS-SWITCH RECOMBINATION; SEQUENCING REVEALS; HUMAN GENOME; BREAKS; CELLS; AID; IDENTIFICATION; REARRANGEMENTS; ORGANIZATION; MECHANISMS AB Recurrent chromosomal translocations underlie both haematopoietic and solid tumours. Their origin has been ascribed to selection of random rearrangements, targeted DNA damage, or frequent nuclear interactions between translocation partners; however, the relative contribution of each of these elements has not been measured directly or on a large scale. Here we examine the role of nuclear architecture and frequency of DNA damage in the genesis of chromosomal translocations by measuring these parameters simultaneously in cultured mouse B lymphocytes. In the absence of recurrent DNA damage, translocations between Igh or Myc and all other genes are directly related to their contact frequency. Conversely, translocations associated with recurrent site-directed DNA damage are proportional to the rate of DNA break formation, as measured by replication protein A accumulation at the site of damage. Thus, non-targeted rearrangements reflect nuclear organization whereas DNA break formation governs the location and frequency of recurrent translocations, including those driving B-cell malignancies. C1 [Klein, Isaac; Jankovic, Mila; Oliveira, Thiago; Bothmer, Anne; Robbiani, Davide F.; Nussenzweig, Michel C.] Rockefeller Univ, Lab Mol Immunol, New York, NY 10065 USA. [Hakim, Ofir; Voss, Ty C.; Hager, Gordon L.] NCI, Lab Receptor Biol & Gene Express, NIH, Bethesda, MD 20892 USA. [Resch, Wolfgang; Yamane, Arito; Kieffer-Kwon, Kyong-Rim; Ansarah-Sobrinho, Camilo; Liang, Genqing; Cobell, Jesse; Nakahashi, Hirotaka; Casellas, Rafael] NCI, NIAMS, NIH, Bethesda, MD 20892 USA. [Oliveira, Thiago] Univ Sao Paulo, Med Sch Ribeirao Preto, Dept Genet, Natl Inst Sci & Technol Stem Cells & Cell Therapy, BR-14051140 Ribeirao Preto, SP, Brazil. [Oliveira, Thiago] Ctr Cell Based Therapy, BR-14051140 Ribeirao Preto, SP, Brazil. [Nussenzweig, Andre] NCI, Lab Genome Integr, NIH, Bethesda, MD 20892 USA. [Nussenzweig, Michel C.] Rockefeller Univ, Howard Hughes Med Inst, New York, NY 10065 USA. [Casellas, Rafael] NCI, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. RP Nussenzweig, MC (reprint author), Rockefeller Univ, Lab Mol Immunol, New York, NY 10065 USA. EM nussen@rockefeller.edu; casellar@mail.nih.gov RI perumal, murugiah/D-1565-2012; Yamane, Arito/A-2959-2013; OI Oliveira, Thiago/0000-0002-2654-0879 FU Starr Foundation; NIH [AI037526]; NIAMS; NCI, NIH FX We thank members of the Casellas and Nussenzweig laboratories for discussions; G. Gutierrez from NIAMS genomics facility for technical assistance. This work was supported in part by a grant from the Starr Foundation to M.C.N., by NIH grant number AI037526 to M.C.N. and the Intramural Research Program of NIAMS and NCI, NIH. M.C.N. is an HHMI investigator. This study made use of the high-performance computational capabilities of the Biowulf Linux cluster at the NIH (http://biowulf.nih.gov), and the resources of NCI's High-Throughput Imaging Facility. NR 28 TC 102 Z9 106 U1 1 U2 16 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0028-0836 EI 1476-4687 J9 NATURE JI Nature PD APR 5 PY 2012 VL 484 IS 7392 BP 69 EP + DI 10.1038/nature10909 PG 8 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 919QN UT WOS:000302343400035 PM 22314321 ER PT J AU Alexander, GM Graef, JD Hammarback, JA Nordskog, BK Burnett, EJ Daunais, JB Bennett, AJ Friedman, DP Suomi, SJ Godwin, DW AF Alexander, G. M. Graef, J. D. Hammarback, J. A. Nordskog, B. K. Burnett, E. J. Daunais, J. B. Bennett, A. J. Friedman, D. P. Suomi, S. J. Godwin, D. W. TI DISRUPTIONS IN SEROTONERGIC REGULATION OF CORTICAL GLUTAMATE RELEASE IN PRIMATE INSULAR CORTEX IN RESPONSE TO CHRONIC ETHANOL AND NURSERY REARING SO NEUROSCIENCE LA English DT Article DE anterior insula; ethanol; serotonin; stress; 5-HT1A ID POSITRON-EMISSION-TOMOGRAPHY; MEDIAL PREFRONTAL CORTEX; EARLY-LIFE STRESS; 5-HYDROXYINDOLEACETIC ACID CONCENTRATIONS; SEROTONIN(1A) RECEPTOR-BINDING; DIMINISHED SOCIAL COMPETENCE; REDUCES SYNAPTIC EXCITATION; RAT BASOLATERAL AMYGDALA; HUMAN CHRONIC-ALCOHOLICS; ANXIETY-PRONE SUBJECTS AB Early-life stress has been shown to increase susceptibility to anxiety and substance abuse. Disrupted activity within the anterior insular cortex (AIC) has been shown to play a role in both of these disorders. Altered serotonergic processing is implicated in controlling the activity levels of the associated cognitive networks. We therefore investigated changes in both serotonin receptor expression and glutamatergic synaptic activity in the AIC of alcohol-drinking rhesus monkeys. We studied tissues from male rhesus monkeys raised under two conditions: Male rhesus monkeys (1) "mother reared" (MR) by adult females (n=9) or (2) "Nursery reared" (NR), that is, separated from their mothers and reared as a separate group under surrogate/peer-reared conditions (n=9). The NR condition represents a long-standing and well-validated nonhuman primate model of early life stress. All monkeys were trained to self-administer ethanol (4% w/v) or an isocaloric maltose dextrin control solution. Subsets from each rearing condition were then given daily access to ethanol, water, or maltose dextrin for 12 months. Tissues were collected at necropsy and were further analyzed. Using real time RT-PCR we found that ethanol-naive, NR monkeys had lower AIC levels of 5-HT1A and 5-HT2A receptor mRNA compared with ethanol-naive, MR animals. Although NR monkeys consumed more ethanol over the 12-month period compared with MR animals, both MR and NR animals expressed greater 5-HT1A and 5-HT2A receptor mRNA levels following chronic alcohol self-administration. The interaction between nursery-rearing conditions and alcohol consumption resulted in a significant enhancement of both 5-HT1A and 5-HT2A receptor mRNA levels such that lower expression levels observed in nursery-rearing conditions were not found in the alcohol self-administration group. Using voltage clamp recordings in the whole cell configuration we recorded excitatory postsynaptic currents in both ethanol-naive and chronic self-administration groups of NR and MR monkeys. Both groups that self-administered ethanol showed greater glutamatergic activity within the AIC. This AIC hyperactivity in MR alcohol-consuming monkeys was accompanied by an increased sensitivity to regulation by presynaptic 5-HT1A receptors that was not apparent in the ethanol-naive, MR group. Our data indicate that chronic alcohol consumption leads to greater AIC activity and may indicate a compensatory upregulation of presynaptic 5-HT1A receptors. Our results also indicate that AIC activity may be less effectively regulated by 5-HT in ethanol-naive NR animals than in NR monkeys in response to chronic ethanol self-administration. These data suggest possible mechanisms for increased alcohol seeking and possible addiction potential among young adults who had previously experienced early-life stress that include disruptions in both AIC activity and serotonin system dynamics. (C) 2012 IBRO. Published by Elsevier Ltd. All rights reserved. C1 [Hammarback, J. A.; Nordskog, B. K.; Godwin, D. W.] Wake Forest Univ, Bowman Gray Sch Med, Dept Neurobiol & Anat, Winston Salem, NC 27157 USA. [Alexander, G. M.] Duke Univ, Med Ctr, Dept Neurobiol, Durham, NC 27710 USA. [Graef, J. D.; Burnett, E. J.] Wake Forest Univ, Bowman Gray Sch Med, Neurosci Program, Winston Salem, NC 27157 USA. [Daunais, J. B.; Bennett, A. J.; Friedman, D. P.] Wake Forest Univ, Bowman Gray Sch Med, Dept Physiol & Pharmacol, Winston Salem, NC 27157 USA. [Suomi, S. J.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Comparat Ethol Lab, NIH, Anim Ctr, Poolesville, MD 20837 USA. RP Godwin, DW (reprint author), Wake Forest Univ, Bowman Gray Sch Med, Dept Neurobiol & Anat, Med Ctr Blvd, Winston Salem, NC 27157 USA. EM dgodwin@wakehealth.edu RI Reis, Aline/G-9573-2012; OI Burnett, Elizabeth/0000-0001-5037-7576 FU NIH [AA014106, AA015568, AA016748, AA016852, AA017056, EY018159]; Tab Williams Family Fund FX We thank Dr. Satoru Hayasaka for statistical support. These studies were supported by NIH grants AA014106 and AA015568 (D.P.F.), AA016748 (J.B.D.), AA016852, AA017056, EY018159, and the Tab Williams Family Fund (D.W.G.). NR 112 TC 2 Z9 2 U1 1 U2 4 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0306-4522 J9 NEUROSCIENCE JI Neuroscience PD APR 5 PY 2012 VL 207 BP 167 EP 181 DI 10.1016/j.neuroscience.2012.01.027 PG 15 WC Neurosciences SC Neurosciences & Neurology GA 917UB UT WOS:000302203000014 PM 22305886 ER PT J AU Mejias-Aponte, CA Kiyatkin, EA AF Mejias-Aponte, C. A. Kiyatkin, E. A. TI VENTRAL TEGMENTAL AREA NEURONS ARE EITHER EXCITED OR INHIBITED BY COCAINE'S ACTIONS IN THE PERIPHERAL NERVOUS SYSTEM SO NEUROSCIENCE LA English DT Article DE cocaine methiodide; peripheral nervous system; cocaine; ventral tegmental area; single-unit recordings ID MIDBRAIN DOPAMINE NEURONS; FREELY MOVING RATS; NUCLEUS-ACCUMBENS NEURONS; INTRAVENOUS COCAINE; SUBSTANTIA-NIGRA; IMPULSE ACTIVITY; SODIUM-CHANNELS; EXTRACELLULAR ELECTROPHYSIOLOGY; NONDOPAMINERGIC NEURONS; SYNAPTIC-TRANSMISSION AB Cocaine's multiple pharmacological substrates are ubiquitously present in the peripheral and central nervous system. Thus, upon its administration, cocaine acts in the periphery before directly acting in the brain. We determined whether cocaine alters ventral tegmental area (VTA) neuronal activity via its peripheral actions. In urethane-anesthetized rats, we recorded VTA neuron's responses to intravenous injections of two cocaine analogs: cocaine-hydrochloride (HCl, 0.25 mg/kg), which readily cross the blood brain barrier (BBB), and cocaine-methiodide (MI, 0.33 mg/kg), which does not cross the BBB. Both cocaine analogs produced sustained changes in discharge rates that began 5 s after the initiation of a 10-s drug infusion. Within the first 90 s post-injection, the magnitudes of neuronal responsiveness of both cocaine analogs were comparable, but later the effects of cocaine-HCl were stronger and persisted longer than those of cocaine-MI. The proportion of neurons responsive to cocaine-HCl was twice that of cocaine-MI (74% and 35%, respectively). Both analogs also differed in their response onsets. Cocaine-MI rarely evoked responses after 1 min, whereas cocaine-HCl continued to evoke responses within 3 min post-injection. VTA neurons were either excited or inhibited by both cocaine analogs. Most units responsive to cocaine-MI, regardless of whether they were excited or inhibited, had electrophysiological characteristics of putative dopamine (DA) neurons. Units inhibited by cocaine-HCl also had characteristics of DA neurons, whereas excited neurons had widely varying action potential durations and discharge rates. Cocaine-MI and cocaine-HCl each produced changes in VTA neuron activity under full DA receptor blockade. However, the duration of inhibition was shortened and the number of excitations increased, and they occurred with an earlier onset during DA receptor blockade. These findings indicate that cocaine acts peripherally with a short latency and alters the activity of VTA neurons before its well-known direct actions in the brain. Published by Elsevier Ltd on behalf of IBRO. C1 [Mejias-Aponte, C. A.; Kiyatkin, E. A.] NIDA, Behav Neurosci Branch, Intramural Res Program, NIH,DHHS,Triad Technol Ctr, Baltimore, MD 21224 USA. RP Mejias-Aponte, CA (reprint author), NIDA, Behav Neurosci Branch, Intramural Res Program, NIH,DHHS,Triad Technol Ctr, Suite 2200,333 Cassell Dr, Baltimore, MD 21224 USA. EM mejiasca@mail.nih.gov FU National Institute on Drug Abuse FX This work was supported by the National Institute on Drug Abuse, Intramural Research Program. We thank Cameron Good, Carl Lupica, and Roy Wise for their insight and comments on the manuscript and for their helpful editorial assistance. We also thank Mary Pfeiffer for her helpful editorial assistance. NR 77 TC 3 Z9 3 U1 2 U2 5 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0306-4522 J9 NEUROSCIENCE JI Neuroscience PD APR 5 PY 2012 VL 207 BP 182 EP 197 DI 10.1016/j.neuroscience.2012.01.026 PG 16 WC Neurosciences SC Neurosciences & Neurology GA 917UB UT WOS:000302203000015 PM 22300980 ER PT J AU Wu, J Lou, H Alerte, TNM Stachowski, EK Chen, J Singleton, AB Hamilton, RL Perez, RG AF Wu, J. Lou, H. Alerte, T. N. M. Stachowski, E. K. Chen, J. Singleton, A. B. Hamilton, R. L. Perez, R. G. TI LEWY-LIKE AGGREGATION OF alpha-SYNUCLEIN REDUCES PROTEIN PHOSPHATASE 2A ACTIVITY IN VITRO AND IN VIVO SO NEUROSCIENCE LA English DT Article DE synucleinopathy; hyperphosphorylation; dephosphorylation; phosphatase; enzymatic regulation ID TYROSINE-HYDROXYLASE PHOSPHORYLATION; FAMILIAL PARKINSONS-DISEASE; ALZHEIMER-DISEASE; NACP/ALPHA-SYNUCLEIN; TAU PHOSPHORYLATION; INCLUSION FORMATION; TRANSGENIC MICE; BODY DISEASE; PP2A; SUBUNIT AB alpha-synuclein (alpha-Syn) is a chaperone-like protein that is highly implicated in Parkinson's disease (PD) as well as in dementia with Lewy bodies (DLB). Rare forms of PD occur in individuals with mutations of alpha-Syn or triplication of wild type alpha-Syn, and in both PD and DLB the intraneuronal inclusions known as Lewy bodies contain aggregated alpha-Syn that is highly phosphorylated on serine 129. In neuronal cells and in the brains of alpha-Syn overexpressing transgenic mice, soluble alpha-Syn stimulates the activity of protein phosphatase 2A (PP2A), a major serine/threonine phosphatase. Serine 129 phosphorylation of alpha-Syn attenuates its stimulatory effects on PP2A and also accelerates alpha-Syn aggregation; however, it is unknown if aggregation of alpha-Syn into Lewy bodies impairs PP2A activity. To assess for this, we measured the impact of alpha-Syn aggregation on PP2A activity in vitro and in vivo. In cell-free assays, aggregated alpha-Syn had similar to 50% less PP2A stimulatory effects than soluble recombinant alpha-Syn. Similarly in DLB and alpha-Syn triplication brains, which contain robust alpha-Syn aggregation with high levels of serine 129 phosphorylation, PP2A activity was also similar to 50% attenuated. As alpha-Syn normally stimulates PP2A activity, our data suggest that overexpression of alpha-Syn or sequestration of alpha-Syn into Lewy bodies has the potential to alter the phosphorylation state of key PP2A substrates; raising the possibility that all forms of synucleinopathy will benefit from treatments aimed at optimizing PP2A activity. (C) 2012 IBRO. Published by Elsevier Ltd. All rights reserved. C1 [Wu, J.; Lou, H.; Alerte, T. N. M.; Stachowski, E. K.; Chen, J.; Perez, R. G.] Univ Pittsburgh, Sch Med, Dept Neurol, Pittsburgh, PA 15261 USA. [Perez, R. G.] Univ Pittsburgh, Sch Med, Dept Pharmacol & Chem Biol, Pittsburgh, PA USA. [Hamilton, R. L.] Univ Pittsburgh, Sch Med, Dept Pathol, Pittsburgh, PA USA. [Wu, J.; Lou, H.; Alerte, T. N. M.; Stachowski, E. K.; Chen, J.; Perez, R. G.] Univ Pittsburgh, Sch Med, Pittsburgh Inst Neurodegenerat Dis, Pittsburgh, PA 15260 USA. [Wu, J.] Fudan Univ, Huashan Hosp, Dept Neurol, Shanghai 200433, Peoples R China. [Lou, H.] Shandong Univ, Dept Pharmacol, Sch Med, Jinan 250012, Shandong, Peoples R China. [Singleton, A. B.] NIA, Neurogenet Lab, NIH, Bethesda, MD 20892 USA. RP Perez, RG (reprint author), Texas Tech Univ, Hlth Sci Ctr, Ctr Excellence Neurosci, Paul L Foster Sch Med, Med Sci Bldg 1,Suite 4002,5001 El Paso Dr, El Paso, TX 79905 USA. EM ruth.g.perez@ttuhsc.edu RI Singleton, Andrew/C-3010-2009 FU University of Pittsburgh Alzheimer's Disease Research Center - National Institutes of Health [P50 AG005133]; National Institute of Neurological Disorders and Stroke [R01 [NS42094]]; China Scholarship Council; Foundation for Excellent Young and Middle-Aged Scientists of Shandong Province [BS2010YY036]; National Institute on Aging-National Institutes of Health [Z01 AG000957-05] FX We thank W Halfter for the dialysis advice, J Worley for preparing human cortex slides, S Slusher for technical help, K Farrell and A Fisher for insightful comments, and E Villanueva for editorial assistance. This work is dedicated to MJ Fox, R Byer, J Cordy, and to the memory of L "Rusty" Lanelli and was supported by a seed award from the University of Pittsburgh Alzheimer's Disease Research Center - National Institutes of Health [P50 AG005133, to R.G.P.]; National Institute of Neurological Disorders and Stroke R01 [NS42094, to R.G.P.]; China Scholarship Council [to LH]; Foundation for Excellent Young and Middle-Aged Scientists of Shandong Province [BS2010YY036, to LH]; and an Intramural Research Program of the National Institute on Aging-National Institutes of Health [Z01 AG000957-05, to AS]. The funding agencies played no role in study design; collection, analysis and interpretation of data; nor in writing the report or in decision to submit the paper for publication. NR 68 TC 20 Z9 20 U1 0 U2 3 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0306-4522 J9 NEUROSCIENCE JI Neuroscience PD APR 5 PY 2012 VL 207 BP 288 EP 297 DI 10.1016/j.neuroscience.2012.01.028 PG 10 WC Neurosciences SC Neurosciences & Neurology GA 917UB UT WOS:000302203000024 PM 22326202 ER PT J AU Kaplan, RM Satterfield, JM Kington, RS AF Kaplan, Robert M. Satterfield, Jason M. Kington, Raynard S. TI Building a Better Physician - The Case for the New MCAT SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Editorial Material C1 [Kaplan, Robert M.] NIH, Off Behav & Social Sci Res, Bethesda, MD 20892 USA. [Satterfield, Jason M.] Univ Calif San Francisco, Dept Med, San Francisco, CA USA. [Kington, Raynard S.] Grinnell Coll, Off President, Grinnell, IA 50112 USA. RP Kaplan, RM (reprint author), NIH, Off Behav & Social Sci Res, Bldg 10, Bethesda, MD 20892 USA. NR 5 TC 25 Z9 25 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 APR 5 PY 2012 VL 366 IS 14 BP 1265 EP 1268 PG 4 WC Medicine, General & Internal SC General & Internal Medicine GA 919QJ UT WOS:000302343000002 PM 22475589 ER PT J AU Haynes, BF Gilbert, PB McElrath, MJ Zolla-Pazner, S Tomaras, GD Alam, SM Evans, DT Montefiori, DC Karnasuta, C Sutthent, R Liao, HX DeVico, AL Lewis, GK Williams, C Pinter, A Fong, Y Janes, H DeCamp, A Huang, YD Rao, M Billings, E Karasavvas, N Robb, ML Ngauy, V de Souza, MS Paris, R Ferrari, G Bailer, RT Soderberg, KA Andrews, C Berman, PW Frahm, N De Rosa, SC Alpert, MD Yates, NL Shen, XY Koup, RA Pitisuttithum, P Kaewkungwal, J Nitayaphan, S Rerks-Ngarm, S Michael, NL Kim, JH AF Haynes, Barton F. Gilbert, Peter B. McElrath, M. Juliana Zolla-Pazner, Susan Tomaras, Georgia D. Alam, S. Munir Evans, David T. Montefiori, David C. Karnasuta, Chitraporn Sutthent, Ruengpueng Liao, Hua-Xin DeVico, Anthony L. Lewis, George K. Williams, Constance Pinter, Abraham Fong, Youyi Janes, Holly DeCamp, Allan Huang, Yunda Rao, Mangala Billings, Erik Karasavvas, Nicos Robb, Merlin L. Ngauy, Viseth de Souza, Mark S. Paris, Robert Ferrari, Guido Bailer, Robert T. Soderberg, Kelly A. Andrews, Charla Berman, Phillip W. Frahm, Nicole De Rosa, Stephen C. Alpert, Michael D. Yates, Nicole L. Shen, Xiaoying Koup, Richard A. Pitisuttithum, Punnee Kaewkungwal, Jaranit Nitayaphan, Sorachai Rerks-Ngarm, Supachai Michael, Nelson L. Kim, Jerome H. TI Immune-Correlates Analysis of an HIV-1 Vaccine Efficacy Trial SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Article ID IMMUNODEFICIENCY-VIRUS; V1/V2 DOMAIN; ANTIBODY; PROTECTION; GP120; INFECTION; RESPONSES; ENVELOPE; MONKEYS; SIV AB BACKGROUND In the RV144 trial, the estimated efficacy of a vaccine regimen against human immunodeficiency virus type 1 (HIV-1) was 31.2%. We performed a case-control analysis to identify antibody and cellular immune correlates of infection risk. METHODS In pilot studies conducted with RV144 blood samples, 17 antibody or cellular assays met prespecified criteria, of which 6 were chosen for primary analysis to determine the roles of T-cell, IgG antibody, and IgA antibody responses in the modulation of infection risk. Assays were performed on samples from 41 vaccinees who became infected and 205 uninfected vaccinees, obtained 2 weeks after final immunization, to evaluate whether immune-response variables predicted HIV-1 infection through 42 months of follow-up. RESULTS Of six primary variables, two correlated significantly with infection risk: the binding of IgG antibodies to variable regions 1 and 2 (V1V2) of HIV-1 envelope proteins (Env) correlated inversely with the rate of HIV-1 infection (estimated odds ratio, 0.57 per 1-SD increase; P = 0.02; q = 0.08), and the binding of plasma IgA antibodies to Env correlated directly with the rate of infection (estimated odds ratio, 1.54 per 1-SD increase; P = 0.03; q = 0.08). Neither low levels of V1V2 antibodies nor high levels of Env-specific IgA antibodies were associated with higher rates of infection than were found in the placebo group. Secondary analyses suggested that Env-specific IgA antibodies may mitigate the effects of potentially protective antibodies. CONCLUSIONS This immune-correlates study generated the hypotheses that V1V2 antibodies may have contributed to protection against HIV-1 infection, whereas high levels of Env-specific IgA antibodies may have mitigated the effects of protective antibodies. Vaccines that are designed to induce higher levels of V1V2 antibodies and lower levels of Env-specific IgA antibodies than are induced by the RV144 vaccine may have improved efficacy against HIV-1 infection. C1 [Haynes, Barton F.; Tomaras, Georgia D.; Alam, S. Munir; Montefiori, David C.; Liao, Hua-Xin; Ferrari, Guido; Soderberg, Kelly A.; Yates, Nicole L.; Shen, Xiaoying] Duke Univ, Human Vaccine Inst, Durham, NC 27710 USA. [Haynes, Barton F.; Tomaras, Georgia D.; Alam, S. Munir; Montefiori, David C.; Liao, Hua-Xin; Ferrari, Guido; Soderberg, Kelly A.; Yates, Nicole L.; Shen, Xiaoying] Duke Univ, Sch Med, Ctr HIV AIDS Vaccine Immunol, Durham, NC 27710 USA. [Gilbert, Peter B.; Fong, Youyi; Janes, Holly; DeCamp, Allan; Huang, Yunda] Fred Hutchinson Canc Res Ctr, Stat Ctr HIV AIDS Res & Prevent, Seattle, WA 98104 USA. [McElrath, M. Juliana; Frahm, Nicole; De Rosa, Stephen C.] Fred Hutchinson Canc Res Ctr, Div Clin Res, Vaccine & Infect Dis Div, Seattle, WA 98104 USA. [Zolla-Pazner, Susan; Williams, Constance] Vet Affairs New York Harbor Healthcare Syst, New York, NY USA. [Zolla-Pazner, Susan; Williams, Constance] NYU, Sch Med, Dept Pathol, New York, NY USA. [Evans, David T.; Alpert, Michael D.] Harvard Univ, Sch Med, New England Reg Primate Ctr, Dept Microbiol & Immunobiol, Southborough, MA 01772 USA. [Rao, Mangala; Billings, Erik; Robb, Merlin L.; Paris, Robert; Andrews, Charla; Michael, Nelson L.; Kim, Jerome H.] Walter Reed Army Inst Res, US Mil Res Program, Silver Spring, MD USA. [Bailer, Robert T.; Koup, Richard A.] NIAID, Vaccine Res Ctr, NIH, Bethesda, MD 20892 USA. [Karnasuta, Chitraporn; Karasavvas, Nicos; Ngauy, Viseth; de Souza, Mark S.] Armed Forces Res Inst Med Sci, US Army Component, Bangkok 10400, Thailand. [Nitayaphan, Sorachai] Armed Forces Res Inst Med Sci, Royal Thai Army, Bangkok 10400, Thailand. [Sutthent, Ruengpueng] Siriraj Hosp, Dept Microbiol, Natl HIV Repository & Bioinformat Ctr, Bangkok, Thailand. [Pitisuttithum, Punnee; Kaewkungwal, Jaranit] Mahidol Univ, Fac Trop Med, Bangkok 10700, Thailand. [Rerks-Ngarm, Supachai] Minist Publ Hlth, Dept Dis Control, Nonthaburi, Thailand. [Berman, Phillip W.] Univ Calif Santa Cruz, Dept Biomol Engn, Santa Cruz, CA 95064 USA. [DeVico, Anthony L.; Lewis, George K.] Univ Maryland, Sch Med, Inst Human Virol, Baltimore, MD 21201 USA. [Pinter, Abraham] Univ Med & Dent New Jersey, New Jersey Med Sch, Newark, NJ 07103 USA. RP Haynes, BF (reprint author), Duke Univ, Med Ctr, Duke Human Vaccine Inst, 2 Genome Ct,Box 103020, Durham, NC 27710 USA. EM hayne002@mc.duke.edu RI Ferrari, Guido/A-6088-2015; Tomaras, Georgia/J-5041-2016 FU Bill and Melinda Gates Foundation Collaboration for AIDS Vaccine Discovery; U.S. Army Medical Research and Materiel Command; NIAID [Y1-AI-2642-12, U01-AI-067854]; Henry M. Jackson Foundation for the Advancement of Military Medicine; Department of Defense [W81XWH-07-2-0067]; HIV Vaccine Trials Network Laboratory [UM1-AI-068618] FX Supported in part by grants from the Bill and Melinda Gates Foundation Collaboration for AIDS Vaccine Discovery (to Drs. Haynes, Koup, and Montefiori); an interagency agreement between the U.S. Army Medical Research and Materiel Command and the NIAID (Y1-AI-2642-12); a cooperative agreement between the Henry M. Jackson Foundation for the Advancement of Military Medicine and the Department of Defense (W81XWH-07-2-0067); and grants from the NIAID to the Center for HIV/AIDS Vaccine Immunology (U01-AI-067854) and the HIV Vaccine Trials Network Laboratory Program (UM1-AI-068618). NR 40 TC 724 Z9 742 U1 10 U2 96 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 APR 5 PY 2012 VL 366 IS 14 BP 1275 EP 1286 PG 12 WC Medicine, General & Internal SC General & Internal Medicine GA 919QJ UT WOS:000302343000005 PM 22475592 ER PT J AU Somerville, RPT Devillier, L Parkhurst, MR Rosenberg, SA Dudley, ME AF Somerville, Robert P. T. Devillier, Laura Parkhurst, Maria R. Rosenberg, Steven A. Dudley, Mark E. TI Clinical scale rapid expansion of lymphocytes for adoptive cell transfer therapy in the WAVE (R) bioreactor SO JOURNAL OF TRANSLATIONAL MEDICINE LA English DT Article DE Human; T Cells; Tumor Immunity; T Cell Receptors; Adoptive Immunotherapy ID CD8(+) T-CELLS; RECOMBINANT INTERLEUKIN-2 THERAPY; TUMOR-INFILTRATING LYMPHOCYTES; METASTATIC MELANOMA; CANCER REGRESSION; ANTIGEN; IMMUNOTHERAPY; CULTURES; RESPONSES; EFFICACY AB Background: To simplify clinical scale lymphocyte expansions, we investigated the use of the WAVE (R), a closed system bioreactor that utilizes active perfusion to generate high cell numbers in minimal volumes. Methods: We have developed an optimized rapid expansion protocol for the WAVE bioreactor that produces clinically relevant numbers of cells for our adoptive cell transfer clinical protocols. Results: TIL and genetically modified PBL were rapidly expanded to clinically relevant scales in both static bags and the WAVE bioreactor. Both bioreactors produced comparable numbers of cells; however the cultures generated in the WAVE bioreactor had a higher percentage of CD4+ cells and had a less activated phenotype. Conclusions: The WAVE bioreactor simplifies the process of rapidly expanding tumor reactive lymphocytes under GMP conditions, and provides an alternate approach to cell generation for ACT protocols. C1 [Somerville, Robert P. T.; Devillier, Laura; Parkhurst, Maria R.; Rosenberg, Steven A.; Dudley, Mark E.] NCI, Surg Branch, NIH, Bethesda, MD 20892 USA. RP Dudley, ME (reprint author), NCI, Surg Branch, NIH, Bldg 10, Bethesda, MD 20892 USA. EM DudleyM@mail.nih.gov FU National Cancer Institute; Adelson Medical Research Foundation FX This research was supported in part by the intramural research program of the National Cancer Institute. Robert Somerville is supported by the Adelson Medical Research Foundation. We would like to thank Kate Hogan, Michelle Langhan, Thomas Shelton, Azam Nahvi, Linda Parker, Colin Gross and Marcos Garcia for assisting with this research. NR 34 TC 19 Z9 20 U1 0 U2 13 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1479-5876 J9 J TRANSL MED JI J. Transl. Med. PD APR 4 PY 2012 VL 10 AR 69 DI 10.1186/1479-5876-10-69 PG 11 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 975OL UT WOS:000306520500001 PM 22475724 ER PT J AU Cheng, C Wang, LS Gall, JGD Nason, M Schwartz, RM McElrath, J DeRosa, SC Hural, J Corey, L Buchbinder, SP Nabel, GJ AF Cheng, Cheng Wang, LingShu Gall, Jason G. D. Nason, Martha Schwartz, Richard M. McElrath, Juliana DeRosa, Steven C. Hural, John Corey, Lawrence Buchbinder, Susan P. Nabel, Gary J. TI Decreased Pre-existing Ad5 Capsid and Ad35 Neutralizing Antibodies Increase HIV-1 Infection Risk in the Step Trial Independent of Vaccination SO PLOS ONE LA English DT Article ID ADENOVIRUS SEROTYPE 5; T-CELLS; SOLUBLE ANTIGENS; GENE-THERAPY; IMMUNITY; VECTORS; IMMUNIZATION; VOLUNTEERS; EXPANSION; HUMANS AB Background: The Step trial raised the possibility that uncircumcised men with pre-existing Ad5 neutralizing antibodies carried an increased risk of HIV infection after vaccination. Thus, understanding Ad seropositivity in humans is important to the development of an AIDS vaccine. Here, we analyze the impact of different Ad5-specific neutralizing antibodies on immune function and clinical outcome. Methods and Findings: Ad seropositivity in the Step trial volunteers was analyzed using chimeric rAd5/35 vectors to characterize their specificity for Ad5 fiber and non-fiber external (capsid) proteins. Immune responses and HIV seropositivity were correlated with the specificity of Ad5-neutralizing antibodies. Neutralizing antibodies induced by the vaccine in Ad5 seronegative subjects were directed preferentially to Ad5 capsid proteins, although some fiber-neutralizing antibodies could be detected. Pre-vaccination Ad5 serostatus did not affect the capsid-directed response after three vaccinations. In contrast, anti-fiber antibody titers were significantly higher in volunteers who were Ad5 seropositive prior to vaccination. Those Ad5 seropositive subjects who generated anti-capsid responses showed a marked reduction in vaccine-induced CD8 responses. Unexpectedly, anti-vector immunity differed qualitatively in Ad5 seropositive participants who became HIV-1 infected compared to uninfected case controls; Ad5 seropositive participants who later acquired HIV had lower neutralizing antibodies to capsid. Moreover, Ad35 seropositivity was decreased in HIV-infected subjects compared with uninfected case controls, while seroprevalence for other serotypes including Ad14, Ad28 and Ad41 was similar in both groups. Conclusions: Together, these findings suggest that the case subjects were less immunologically responsive prior to infection. Subjects infected during the Step trial had qualitative differences in immunity that increased their risk of HIV-1 infection independent of vaccination. C1 [Cheng, Cheng; Wang, LingShu; Schwartz, Richard M.; Nabel, Gary J.] NIAID, Vaccine Res Ctr, NIH, Bethesda, MD 20892 USA. [Nason, Martha] NIAID, Biostat Res Branch, NIH, Bethesda, MD 20892 USA. [Gall, Jason G. D.] GenVec Inc, Gaithersburg, MD USA. [McElrath, Juliana; DeRosa, Steven C.; Hural, John; Corey, Lawrence] Fred Hutchinson Canc Res Ctr, Vaccine & Infect Dis Div, Seattle, WA 98104 USA. [McElrath, Juliana; DeRosa, Steven C.; Hural, John; Corey, Lawrence; Buchbinder, Susan P.] HIV Vaccine Trials Network, Seattle, WA USA. [Buchbinder, Susan P.] San Francisco Dept Publ Hlth, HIV Res Sect, San Francisco, CA USA. RP Cheng, C (reprint author), NIAID, Vaccine Res Ctr, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA. EM gnabel@nih.gov FU National Institutes of Health intramural research FX The study was funded by National Institutes of Health intramural research. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 25 TC 11 Z9 11 U1 0 U2 3 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA SN 1932-6203 J9 PLOS ONE JI PLoS One PD APR 4 PY 2012 VL 7 IS 4 AR e33969 DI 10.1371/journal.pone.0033969 PG 9 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 953GO UT WOS:000304855200028 ER PT J AU O'Seaghdha, CM Hwang, SJ Vasan, RS Larson, MG Hoffmann, U Wang, TJ Fox, CS AF O'Seaghdha, Conall M. Hwang, Shih-Jen Vasan, Ramachandran S. Larson, Martin G. Hoffmann, Udo Wang, Thomas J. Fox, Caroline S. TI Correlation of renin angiotensin and aldosterone system activity with subcutaneous and visceral adiposity: the framingham heart study SO BMC ENDOCRINE DISORDERS LA English DT Article ID BODY-MASS INDEX; ESSENTIAL-HYPERTENSION; INSULIN-RESISTANCE; CARDIOVASCULAR-DISEASE; TISSUE COMPARTMENTS; SERUM ALDOSTERONE; RISK-FACTORS; OBESITY; ADULTS; DIET AB Background: Animal studies suggest that local adipocyte-mediated activity of the renin-angiotensin-aldosterone system (RAAS) contributes to circulating levels, and may promote the development of obesity-related hypertension in rodents. Methods: We examined relations of systemic RAAS activity, as assessed by circulating plasma renin activity (PRA), serum aldosterone level, and aldosterone: renin ratio (ARR), with specific regional adiposity measures in a large, community-based sample. Third Generation Framingham Heart Study participants underwent multidetector computed tomography assessment of SAT and VAT volumes during Exam 1 (2002 and 2005). PRA and serum aldosterone were measured after approximately 10 minutes of supine rest; results were log-transformed for analysis. Correlation coefficients between log-transformed RAAS measures and adiposity measurements were calculated, adjusted for age and sex. Partial correlations between log-transformed RAAS measures and adiposity measurements were also calculated, adjusted for standard CVD risk factors. Results: Overall, 992 women and 897 men were analyzed (mean age 40 years; 7% hypertension; 3% diabetes). No associations were observed with SAT (renin r = 0.04, p = 0.1; aldosterone r = -0.01, p = 0.6) or VAT (renin r = 0.03, p = 0.2; aldosterone r = -0.03, p = 0.2). Similar results were observed for ARR, in sex-stratified analyses, and for BMI and waist circumference. Non-significant partial correlations were also observed in models adjusted for standard cardiovascular risk factors. Conclusions: Regional adiposity measures were not associated with circulating measures of RAAS activity in this large population-based study. Further studies are required to determine whether adipocyte-derived RAAS components contribute to systemic RAAS activity in humans. C1 [O'Seaghdha, Conall M.; Hwang, Shih-Jen; Vasan, Ramachandran S.; Larson, Martin G.; Wang, Thomas J.; Fox, Caroline S.] Nat Heart Lung & Blood Inst, Framingham Heart Study, Framingham, MA USA. [O'Seaghdha, Conall M.; Hwang, Shih-Jen; Fox, Caroline S.] Ctr Populat Studies, Framingham, MA USA. [O'Seaghdha, Conall M.] Brigham & Womens Hosp, Div Renal, Boston, MA 02115 USA. [O'Seaghdha, Conall M.; Fox, Caroline S.] Harvard Univ, Sch Med, Boston, MA USA. [Larson, Martin G.] Boston Univ, Dept Math & Stat, Boston, MA 02215 USA. [Larson, Martin G.] Boston Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02215 USA. [Hoffmann, Udo] Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. [Wang, Thomas J.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Cardiol, Boston, MA USA. [Fox, Caroline S.] Brigham & Womens Hosp, Div Endocrinol, Boston, MA 02115 USA. RP Fox, CS (reprint author), Nat Heart Lung & Blood Inst, Framingham Heart Study, 73 Mt Wayte Ave Suite 2, Framingham, MA USA. EM foxca@nhlbi.nih.gov OI Larson, Martin/0000-0002-9631-1254; Ramachandran, Vasan/0000-0001-7357-5970 FU National Heart, Lung, and Blood Institute [N01-HC-25195]; [R01-HL-086875] FX The Framingham Heart Study is supported by the National Heart, Lung, and Blood Institute (N01-HC-25195). Dr. Wang is supported by R01-HL-086875. NR 42 TC 12 Z9 12 U1 0 U2 2 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1472-6823 J9 BMC ENDOCR DISORD JI BMC Endocr. Disord. PD APR 4 PY 2012 VL 12 AR 3 DI 10.1186/1472-6823-12-3 PG 7 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 943AN UT WOS:000304092900001 PM 22475205 ER PT J AU Sinka, ME Bangs, MJ Manguin, S Rubio-Palis, Y Chareonviriyaphap, T Coetzee, M Mbogo, CM Hemingway, J Patil, AP Temperley, WH Gething, PW Kabaria, CW Burkot, TR Harbach, RE Hay, SI AF Sinka, Marianne E. Bangs, Michael J. Manguin, Sylvie Rubio-Palis, Yasmin Chareonviriyaphap, Theeraphap Coetzee, Maureen Mbogo, Charles M. Hemingway, Janet Patil, Anand P. Temperley, William H. Gething, Peter W. Kabaria, Caroline W. Burkot, Thomas R. Harbach, Ralph E. Hay, Simon I. TI A global map of dominant malaria vectors SO PARASITES & VECTORS LA English DT Article ID ANOPHELES-FUNESTUS GROUP; BIONOMIC PRECIS; NICHE MODELS; POPULATION; ABUNDANCE; ASSAY; ASIA AB Background: Global maps, in particular those based on vector distributions, have long been used to help visualise the global extent of malaria. Few, however, have been created with the support of a comprehensive and extensive evidence-based approach. Methods: Here we describe the generation of a global map of the dominant vector species (DVS) of malaria that makes use of predicted distribution maps for individual species or species complexes. Results: Our global map highlights the spatial variability in the complexity of the vector situation. In Africa, An. gambiae, An. arabiensis and An. funestus are co-dominant across much of the continent, whereas in the Asian-Pacific region there is a highly complex situation with multi-species coexistence and variable species dominance. Conclusions: The competence of the mapping methodology to accurately portray DVS distributions is discussed. The comprehensive and contemporary database of species-specific spatial occurrence (currently available on request) will be made directly available via the Malaria Atlas Project (MAP) website from early 2012. C1 [Sinka, Marianne E.; Patil, Anand P.; Temperley, William H.; Gething, Peter W.; Hay, Simon I.] Univ Oxford, Spatial Ecol & Epidemiol Grp, Dept Zool, Oxford OX1 3PS, England. [Bangs, Michael J.] PT Freeport Indonesia, Publ Hlth & Malaria Control Dept, Kuala Kencana, Papua, Indonesia. [Manguin, Sylvie] Univ Montpellier I, Inst Rech Dev, Lab Immunophysiopathol Mol Comparee, Fac Pharm,UMR MD3, F-34093 Montpellier, France. [Rubio-Palis, Yasmin] Univ Carabobo, Maracay 2101A, Venezuela. [Rubio-Palis, Yasmin] Minist Poder Popular Salud, Direcc Control Vectores & Fauna Nociva, Lab Ecol Vectores, Maracay, Venezuela. [Chareonviriyaphap, Theeraphap] Kasetsart Univ, Dept Entomol, Fac Agr, Bangkok, Thailand. [Coetzee, Maureen] Univ Witwatersrand, Malaria Entomol Res Unit, Sch Pathol, Fac Hlth Sci, Johannesburg, South Africa. [Chareonviriyaphap, Theeraphap] Natl Hlth Lab Serv, Natl Inst Communicable Dis, Vector Control Reference Unit, ZA-2131 Johannesburg, South Africa. [Mbogo, Charles M.] KEMRI Wellcome Trust Programme, Ctr Geog Med Res Coast, Kilifi, Kenya. [Hemingway, Janet] Univ Liverpool, Liverpool Sch Trop Med, Liverpool L3 5QA, Merseyside, England. [Kabaria, Caroline W.] Univ Oxford, Malaria Publ Hlth & Epidemiol Grp, Kenyatta Natl Hosp Grounds,Ctr Geog Med, Wellcome Trust Collaborat Programme,KEMRI, Nairobi, Kenya. [Burkot, Thomas R.] James Cook Univ, Trop Hlth Alliance, Townsville, Qld, Australia. [Harbach, Ralph E.] Nat Hist Museum, Dept Entomol, London SW7 5BD, England. [Hay, Simon I.] NIH, Fogarty Int Ctr, Bethesda, MD 20892 USA. RP Sinka, ME (reprint author), Univ Oxford, Spatial Ecol & Epidemiol Grp, Dept Zool, Tinbergen Bldg,S Parks Rd, Oxford OX1 3PS, England. EM marianne.sinka@zoo.ox.ac.uk; simon.hay@zoo.ox.ac.uk RI Burkot, Thomas/C-6838-2013; Manguin, Sylvie/G-1787-2015; Hay, Simon/F-8967-2015; OI Manguin, Sylvie/0000-0002-5925-7164; Hay, Simon/0000-0002-0611-7272; Hemingway, Janet/0000-0002-3200-7173; Gething, Peter/0000-0001-6759-5449 FU Technical Advisory Group; Wellcome Trust [083534, 079091, 091835]; Bill and Melinda Gates Foundation via the VFCNet consortium; RAPIDD of the Science & Technology Directorate, Department of Homeland Security; Fogarty International Center; National Institutes of Health; Wellcome Trust, U.K; Global Fund to fight AIDS, Tuberculosis, and Malaria; University of Oxford-Li Ka Shing Foundation; Oxford Tropical Network FX We wish to thank Robi Okara, Rosalind Howes, Edward Haynes, Philip Mbithi, Owen Yang, Carolynn Tago and Elisabeth Thiveyrat for primary data abstraction and to Katherine Battle and David Pigott for proof reading the manuscript. We are very grateful for insightful comments and encouragement from Anthony Kiszewski on the global and regional composite maps. We also thank unreservedly our Technical Advisory Group for their extended support over the duration of the project. The initial vector database and species distribution maps were created while MES was funded by a project grant from the Wellcome Trust (#083534) to SIH. The current work was conducted with support and funding from the Bill and Melinda Gates Foundation via the VFCNet consortium http://www.vecnet.org/[36], which also provides support for TRB. SIH is funded by a Senior Research Fellowship from the Wellcome Trust (#079091), which also supported CWK and supports PWG. APP and WHT are funded by a Wellcome Trust Biomedical Resources Grant (#091835). SIH and PWG also acknowledge support from the RAPIDD program of the Science & Technology Directorate, Department of Homeland Security, and the Fogarty International Center, National Institutes of Health http://www.fic.nih.gov. This work forms part of the output of the Malaria Atlas Project (MAP, http://www.map.ox.ac.uk), principally funded by the Wellcome Trust, U.K. MAP also acknowledges the support of the Global Fund to fight AIDS, Tuberculosis, and Malaria http://www.theglobalfund.org and grants from the University of Oxford-Li Ka Shing Foundation Global Health Program and the Oxford Tropical Network. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 31 TC 129 Z9 130 U1 8 U2 52 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1756-3305 J9 PARASITE VECTOR JI Parasites Vectors PD APR 4 PY 2012 VL 5 AR 69 DI 10.1186/1756-3305-5-69 PG 11 WC Parasitology SC Parasitology GA 940GM UT WOS:000303878000001 PM 22475528 ER PT J AU Smith, MR Hamson, DK Poort, JE Jordan, CL Breedlove, SM AF Smith, Milo R. Hamson, Dwayne K. Poort, Jessica E. Jordan, Cynthia L. Breedlove, S. Marc TI Ontogeny of androgen receptor expression in spinal nucleus of the bulbocavernosus motoneurons and their target muscles in male mice SO NEUROSCIENCE LETTERS LA English DT Article DE Androgen receptor; Bulbocavernosus; Motoneuron; Sexual differentiation ID LEVATOR ANI MUSCLE; DEVELOPING NEUROMUSCULAR SYSTEM; MALE-RATS; GENITOFEMORAL NERVE; HORMONAL-CONTROL; KNOCKOUT MICE; CELL-DEATH; TESTOSTERONE; IMMUNOREACTIVITY; FLUTAMIDE AB The spinal nucleus of the bulbocavernosus (SNB) in rodents is a neuromuscular system consisting of lumbar motoneurons and the perineal muscles they innervate, the bulbocavernosus and levator ani. This system is present prenatally in both males and females but degenerates postnatally in females because of the lack of perinatal androgens. Whether androgens act on the motoneurons or muscles in the SNB system to promote survival is a longstanding question. Evidence in rats suggests androgens act primarily on the muscles in development, given that the muscles express androgen receptor (AR) before the critical period of androgen-dependent cell rescue, whereas motoneurons develop AR after this period. We now report, based on a novel AR-reporter mouse model, that AR is expressed in the bulbocavernosus muscles of C57/BL6(J) mice as early as embryonic day 15, while, based on AR-immunocytochemistry, SNB motoneurons do not express AR until postnatal day 4. These results indicate that the ontogeny of AR expression in the mouse SNB system resembles that found in rats, suggesting that androgens may also act on perineal muscles in mice to rescue the SNB system. (c) 2012 Elsevier Ireland Ltd. All rights reserved. C1 [Smith, Milo R.; Hamson, Dwayne K.; Poort, Jessica E.; Jordan, Cynthia L.; Breedlove, S. Marc] Michigan State Univ, Neurosci Program, E Lansing, MI 48824 USA. RP Smith, MR (reprint author), NIH, BG 10 RM 2D39,10 Ctr Dr, Bethesda, MD 20892 USA. EM milo.smith@nih.gov FU National Institutes of Health [R01 NS28241, NS045195]; Michigan State University FX We thank Diane Redenius for dedicated research support. This work was made possible by National Institutes of Health Grants R01 NS28241 (SMB) and NS045195 (CLJ) and with the support of the Michigan State University Summer Research Opportunities Program. NR 22 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 APR 4 PY 2012 VL 513 IS 2 BP 119 EP 123 DI 10.1016/j.neulet.2012.01.067 PG 5 WC Neurosciences SC Neurosciences & Neurology GA 929UD UT WOS:000303090300003 PM 22330750 ER PT J AU Wallace, GL Shaw, P Lee, NR Clasen, LS Raznahan, A Lenroot, RK Martin, A Giedd, JN AF Wallace, Gregory L. Shaw, Philip Lee, Nancy Raitano Clasen, Liv S. Raznahan, Armin Lenroot, Rhoshel K. Martin, Alex Giedd, Jay N. TI Distinct Cortical Correlates of Autistic versus Antisocial Traits in a Longitudinal Sample of Typically Developing Youth SO JOURNAL OF NEUROSCIENCE LA English DT Article ID PROCESS SCREENING DEVICE; AUTOMATED 3-D EXTRACTION; PSYCHOPATHIC TRAITS; SPECTRUM DISORDER; SOCIAL COGNITION; MENTAL-HEALTH; CHILDREN; BRAIN; RELIABILITY; VALIDITY AB In humans, behaviors associated with autism and antisociality, disorders characterized by distinct social impairments, can be viewed as quantitative traits that range from frank impairment to normal variation, as found in the general population. Neuroimaging investigations of autism and antisociality demonstrate diagnostically specific aberrant cortical brain structure. However, little is known about structural brain correlates of social behavior in nonclinical populations. Therefore, we sought to determine whether autistic and antisocial traits exhibit dissociable cortical correlates and whether these associations are stable across development among typically developing youth. Three hundred twenty-three typically developing youth (age at first scan: mean = 10.63, SD = 3.71 years) underwent anatomic magnetic resonance imaging (1-6 scans each; total = 742 scans), and provided ratings of autistic and antisocial traits. Higher autistic trait ratings were associated with thinner cortex most prominently in right superior temporal sulcus while higher antisocial trait ratings were associated with thinner cortex in primarily bilateral anterior prefrontal cortices. There was no interaction with age, indicating that these brain-behavior associations were stable across development. Using assessments of both subclinical autistic and subclinical antisocial traits within a large longitudinal sample of typically developing youth, we demonstrate dissociable neuroanatomic correlations that parallel those found in the frank clinical disorders of autism (e. g., superior temporal cortex) and antisociality (e. g., anterior prefrontal cortex). Moreover, these correlations appear to be established in early childhood and remain fixed into early adulthood. These results support the dimensional view of psychopathology and provide neural signatures that can serve as informative endophenotypes for future genetic studies. C1 [Wallace, Gregory L.; Martin, Alex] NIMH, Lab Brain & Cognit, NIH, Bethesda, MD 20892 USA. [Shaw, Philip; Lee, Nancy Raitano; Clasen, Liv S.; Raznahan, Armin; Lenroot, Rhoshel K.; Giedd, Jay N.] NIMH, Child Psychiat Branch, NIH, Bethesda, MD 20892 USA. RP Wallace, GL (reprint author), NIMH, Lab Brain & Cognit, NIH, 10 Ctr Dr,Room 4C104,MSC 1366, Bethesda, MD 20892 USA. EM gregwallace@mail.nih.gov RI martin, alex/B-6176-2009; Raznahan, Armin/F-4534-2012; Giedd, Jay/B-7302-2012; Giedd, Jay/J-9644-2015; Lee, Nancy/M-7492-2016; OI Giedd, Jay/0000-0003-0827-3460; Giedd, Jay/0000-0003-2002-8978; Lee, Nancy/0000-0002-6663-0713; Wallace, Gregory/0000-0003-0329-5054 FU NIH, National Institute of Mental Health FX This research was supported by the Intramural Research Program of the NIH, National Institute of Mental Health. We thank the participants and their families who volunteered their time to contribute to this research. NR 49 TC 27 Z9 28 U1 4 U2 18 PU SOC NEUROSCIENCE PI WASHINGTON PA 11 DUPONT CIRCLE, NW, STE 500, WASHINGTON, DC 20036 USA SN 0270-6474 J9 J NEUROSCI JI J. Neurosci. PD APR 4 PY 2012 VL 32 IS 14 BP 4856 EP 4860 DI 10.1523/JNEUROSCI.6214-11.2012 PG 5 WC Neurosciences SC Neurosciences & Neurology GA 925TD UT WOS:000302783500016 PM 22492041 ER PT J AU Iruarrizaga-Lejarreta, M Varela-Rey, M Lozano, JJ Fernandez-Ramos, D Rodriguez-Ezpeleta, N Embade, N Lu, SC van der Kraan, PM Davidson, ENB Gorospe, M Mirsky, R Jessen, KR Aransay, AM Mato, JM Martinez-Chantar, ML Woodhoo, A AF Iruarrizaga-Lejarreta, Marta Varela-Rey, Marta Jose Lozano, Juan Fernandez-Ramos, David Rodriguez-Ezpeleta, Naiara Embade, Nieves Lu, Shelly C. van der Kraan, Peter M. Davidson, Esmeralda N. Blaney Gorospe, Myriam Mirsky, Rhona Jessen, Kristjan R. Maria Aransay, Ana Mato, Jose M. Martinez-Chantar, Maria L. Woodhoo, Ashwin TI The RNA-Binding Protein Human Antigen R Controls Global Changes in Gene Expression during Schwann Cell Development SO JOURNAL OF NEUROSCIENCE LA English DT Article ID PERIPHERAL NERVOUS-SYSTEM; NF-KAPPA-B; GROWTH-FACTOR-BETA; MESSENGER-RNA; IN-VITRO; EMBRYONIC-DEVELOPMENT; EXTRACELLULAR-MATRIX; WIDE ANALYSIS; CYCLIN D1; KINASE-C AB An important prerequisite to myelination in peripheral nerves is the establishment of one-to-one relationships between axons and Schwann cells. This patterning event depends on immature Schwann cell proliferation, apoptosis, and morphogenesis, which are governed by coordinated changes in gene expression. Here, we found that the RNA-binding protein human antigen R (HuR) was highly expressed in immature Schwann cells, where genome-wide identification of its target mRNAs in vivo in mouse sciatic nerves using ribonomics showed an enrichment of functionally related genes regulating these processes. HuR coordinately regulated expression of several genes to promote proliferation, apoptosis, and morphogenesis in rat Schwann cells, in response to NRG1, TGF beta, and laminins, three major signals implicated in this patterning event. Strikingly, HuR also binds to several mRNAs encoding myelination-related proteins but, contrary to its typical function, negatively regulated their expression, likely to prevent ectopic myelination during development. These functions of HuR correlated with its abundance and subcellular localization, which were regulated by different signals in Schwann cells. C1 [Iruarrizaga-Lejarreta, Marta; Varela-Rey, Marta; Fernandez-Ramos, David; Rodriguez-Ezpeleta, Naiara; Embade, Nieves; Maria Aransay, Ana; Mato, Jose M.; Martinez-Chantar, Maria L.; Woodhoo, Ashwin] Ctr Invest Biomed Red Enfermedades Hepat & Digest, CIC BioGUNE, Derio 48160, Bizkaia, Spain. [Jose Lozano, Juan] Hosp Clin Ctr Esther Koplovitz, Ctr Invest Biomed Red Enfermedades Hepat & Digest, Barcelona 08036, Spain. [Lu, Shelly C.] Univ So Calif, Keck Sch Med, Res Ctr Liver Dis, Div Gastrointestinal & Liver Dis, Los Angeles, CA 90033 USA. [van der Kraan, Peter M.; Davidson, Esmeralda N. Blaney] Radboud Univ Nijmegen, Med Ctr, Dept Rheumatol, Nijmegen Ctr Mol Life Sci,Med Ctr Nijmegen, NL-6525 GA Nijmegen, Netherlands. [Gorospe, Myriam] NIA, Lab Cellular & Immunol, Intramural Res Program, NIH, Baltimore, MD 21224 USA. [Mirsky, Rhona; Jessen, Kristjan R.] UCL, Dept Cell & Dev Biol, London WC1E 6BT, England. RP Woodhoo, A (reprint author), Ctr Invest Biomed Red Enfermedades Hepat & Digest, CIC BioGUNE, Technol Pk Bizkaia, Derio 48160, Bizkaia, Spain. EM awoodhoo@cicbiogune.es RI MATO, JOSE/A-5187-2011; Aransay, Ana/F-8086-2011; Rodriguez-Ezpeleta, Naiara/B-7138-2014; van der Kraan, Peter/D-9115-2011; embade, Nieves/K-5190-2014; woodhoo, ashwin/A-4904-2015; Martinez Chantar, Maria Luz/F-5190-2011; Blaney Davidson, E.N./L-4204-2015; Fernandez-Ramos, David/S-5231-2016 OI Aransay, Ana/0000-0002-8271-612X; Rodriguez-Ezpeleta, Naiara/0000-0001-6735-6755; embade, Nieves/0000-0001-9878-3290; woodhoo, ashwin/0000-0002-8395-2837; Martinez Chantar, Maria Luz/0000-0002-6446-9911; FU Instituto de Salud Carlos III (FIS) [PS09/00094]; Fundacion Cientifica de la Asociacion Espanola Contra el Cancer; Ministry of Science and Innovation, Spain; Royal Society of Great Britain; National Institutes of Health [AT-1576]; Spanish Ministry of Science [SAF2011-29851]; Sanidad Gobierno Vasco; Educacion Gobierno Vasco; Instituto de Salud Carlos III; National Institute on Aging, National Institutes of Health; [PI11/01588] FX This work was supported by grants from Instituto de Salud Carlos III (FIS, PS09/00094; Ministry of Health, Spain), Fundacion Cientifica de la Asociacion Espanola Contra el Cancer (Cancer Infantil), and the Program Ramon y Cajal (Ministry of Science and Innovation, Spain) (A. W.), an International Joint Project grant from the Royal Society of Great Britain (K.R.J., A. W.), National Institutes of Health Grant AT-1576 (S. C. L., M. L. M.-C., J.M.M.), Plan Nacional from the Spanish Ministry of Science SAF2011-29851 (J.M.M.), Sanidad Gobierno Vasco 2012 (M.V.-R.), ETORTEK-2010 (M. L. M.-C.), Sanidad Gobierno Vasco 2008 (M. L. M.-C.), Educacion Gobierno Vasco 2011 (M. L. M.-C.), and PI11/01588 (M. L. M.-C.). Centro de Investigacion Biomedica en Red de Enfermedades Hepaticas y Digestivas is funded by the Instituto de Salud Carlos III. M. G. was supported by the National Institute on Aging-Intramural Research Program, National Institutes of Health. NR 87 TC 4 Z9 4 U1 0 U2 7 PU SOC NEUROSCIENCE PI WASHINGTON PA 11 DUPONT CIRCLE, NW, STE 500, WASHINGTON, DC 20036 USA SN 0270-6474 J9 J NEUROSCI JI J. Neurosci. PD APR 4 PY 2012 VL 32 IS 14 BP 4944 EP 4958 DI 10.1523/JNEUROSCI.5868-11.2012 PG 15 WC Neurosciences SC Neurosciences & Neurology GA 925TD UT WOS:000302783500025 PM 22492050 ER PT J AU Bossert, JM Stern, AL Theberge, FRM Marchant, NJ Wang, HL Morales, M Shaham, Y AF Bossert, Jennifer M. Stern, Anna L. Theberge, Florence R. M. Marchant, Nathan J. Wang, Hui-Ling Morales, Marisela Shaham, Yavin TI Role of Projections from Ventral Medial Prefrontal Cortex to Nucleus Accumbens Shell in Context-Induced Reinstatement of Heroin Seeking SO JOURNAL OF NEUROSCIENCE LA English DT Article ID PHASEOLUS-VULGARIS-LEUKOAGGLUTININ; DOPAMINE D-1-FAMILY RECEPTORS; PRIMING-INDUCED REINSTATEMENT; COCAINE-INDUCED REINSTATEMENT; CUE-INDUCED REINSTATEMENT; C-FOS IMMUNOREACTIVITY; BASOLATERAL AMYGDALA; DRUG-SEEKING; INDUCED RELAPSE; PRELIMBIC CORTEX AB In humans, exposure to contexts previously associated with heroin use can provoke relapse. In rats, exposure to heroin-paired contexts after extinction of drug-reinforced responding in different contexts reinstates heroin seeking. This effect is attenuated by inhibition of glutamate or dopamine transmission in nucleus accumbens shell, or inactivation of ventral medial prefrontal cortex (mPFC). Here, we used an anatomical asymmetrical disconnection procedure to demonstrate that an interaction between glutamatergic projections from ventral mPFC to accumbens shell and local dopamine D-1 postsynaptic receptors contributes to context-induced reinstatement of heroin seeking. We also combined the marker of neuronal activity, Fos, with the retrograde tracer Fluoro-Gold to assess activation in this pathway during context-induced reinstatement. Rats were trained to self-administer heroin for 12 d; drug infusions were paired with a discrete tone-light cue. Lever pressing was subsequently extinguished in a nondrug-associated context in the presence of the discrete cue. Rats were then tested in the heroin- or extinction-associated contexts under extinction conditions. Injections of muscimol + baclofen into ventral mPFC in one hemisphere and D-1-family receptor antagonist SCH 23390 into the contralateral or ipsilateral accumbens shell decreased context-induced reinstatement. Unilateral injections of muscimol + baclofen into ventral mPFC or SCH 23390 into the accumbens shell had no effect. Context-induced reinstatement was associated with increased Fos expression in ventral mPFC neurons, including those projecting to accumbens shell, with higher double-labeling in the ipsilateral projection than in the contralateral projection. Our results demonstrate that activation of glutamatergic projections from ventral mPFC to accumbens shell, previously implicated in inhibition of cocaine relapse, promotes heroin relapse. C1 [Bossert, Jennifer M.; Stern, Anna L.; Theberge, Florence R. M.; Marchant, Nathan J.; Shaham, Yavin] NIDA, Behav Neurosci Branch, Intramural Res Program, NIH,Dept Hlth & Human Serv, Baltimore, MD 21224 USA. [Wang, Hui-Ling; Morales, Marisela] NIDA, Cellular Neurobiol Res Branch, Intramural Res Program, NIH,Dept Hlth & Human Serv, Baltimore, MD 21224 USA. RP Bossert, JM (reprint author), NIDA, Behav Neurosci Branch, Intramural Res Program, NIH,Dept Hlth & Human Serv, 251 Bayview Blvd, Baltimore, MD 21224 USA. EM jbossert@intra.nida.nih.gov RI shaham, yavin/G-1306-2014; OI Marchant, Nathan/0000-0001-8269-0532 FU National Institute on Drug Abuse (NIH, DHHS) FX This work was supported by the Intramural Research Program of the National Institute on Drug Abuse (NIH, DHHS). We thank Brittany Navarre, Carlo Cifani, and Sanya Fanous for their help in conducting the experiments. We also thank Susan Sesack, Stan Floresco, Kue Tseng, Anthony Grace, Patricio O'Donnell, and Bita Moghaddam for helpful advice on anatomical and circuit issues discussed in this paper. NR 85 TC 85 Z9 93 U1 0 U2 6 PU SOC NEUROSCIENCE PI WASHINGTON PA 11 DUPONT CIRCLE, NW, STE 500, WASHINGTON, DC 20036 USA SN 0270-6474 J9 J NEUROSCI JI J. Neurosci. PD APR 4 PY 2012 VL 32 IS 14 BP 4982 EP 4991 DI 10.1523/JNEUROSCI.0005-12.2012 PG 10 WC Neurosciences SC Neurosciences & Neurology GA 925TD UT WOS:000302783500028 PM 22492053 ER PT J AU Kim, T Lee, KI Morris, P Pastor, RW Andersen, OS Im, W AF Kim, Taehoon Lee, Kyu Il Morris, Phillip Pastor, Richard W. Andersen, Olaf S. Im, Wonpil TI Influence of Hydrophobic Mismatch on Structures and Dynamics of Gramicidin A and Lipid Bilayers SO BIOPHYSICAL JOURNAL LA English DT Article ID MEMBRANE-PROTEIN FUNCTION; MOLECULAR-DYNAMICS; H-2 NMR; ENSEMBLE DYNAMICS; CHANNEL LIFETIME; CHAIN DYNAMICS; ION PERMEATION; FORCE-FIELDS; FREE-ENERGY; SIDE-CHAIN AB Gramicidin A (gA) is a 15-amino-acid antibiotic peptide with an alternating L-D sequence, which forms (dimeric) bilayer-spanning, monovalent cation channels in biological membranes and synthetic bilayers. We performed molecular dynamics simulations of gA dimers and monomers in all-atom, explicit dilauroylphosphatidylcholine (DLPC), dimyristoylphosphatidylcholine (DMPC), dioleoylphosphatidylcholine (DOPC), and 1-palmitoy1-2-oleoyl-phosphatidylcholine (POPC) bilayers. The variation in acyl chain length among these different phospholipids provides a way to alter gA-bilayer interactions by varying the bilayer hydrophobic thickness, and to determine the influence of hydrophobic mismatch on the structure and dynamics of both gA channels (and monomeric subunits) and the host bilayers. The simulations show that the channel structure varied little with changes in hydrophobic mismatch, and that the lipid bilayer adapts to the bilayer-spanning channel to minimize the exposure of hydrophobic residues. The bilayer thickness, however, did not vary monotonically as a function of radial distance from the channel. In all simulations, there was an initial decrease in thickness within 4-5 angstrom from the channel, which was followed by an increase in DOPC and POPC or a further decrease in DLPC and DMPC bilayers. The bilayer thickness varied little in the monomer simulations except one of three independent simulations for DMPC and all three DLPC simulations, where the bilayer thinned to allow a single subunit to form a bilayer-spanning water-permeable pore. The radial dependence of local lipid area and bilayer compressibility is also nonmonotonic in the first shell around gA dimers due to gA-phospholipid interactions and the hydrophobic mismatch. Order parameters, acyl chain dynamics, and diffusion constants also differ between the lipids in the first shell and the bulk. The lipid behaviors in the first shell around gA dimers are more complex than predicted from a simple mismatch model, which has implications for understanding the energetics of membrane protein-lipid interactions. C1 [Andersen, Olaf S.] Weill Cornell Med Coll, Dept Physiol & Biophys, New York, NY USA. [Kim, Taehoon; Lee, Kyu Il; Morris, Phillip; Im, Wonpil] Univ Kansas, Dept Mol Biosci, Lawrence, KS 66045 USA. [Kim, Taehoon; Lee, Kyu Il; Morris, Phillip; Im, Wonpil] Univ Kansas, Ctr Bioinformat, Lawrence, KS 66045 USA. [Pastor, Richard W.] NHLBI, Lab Computat Biol, NIH, Bethesda, MD 20892 USA. RP Andersen, OS (reprint author), Weill Cornell Med Coll, Dept Physiol & Biophys, New York, NY USA. EM sparre@med.cornell.edu; wonpil@ku.edu FU National Science Foundation [MCB-0918374]; Purdue University (National Science Foundation) [OCI-0503992]; National Institutes of Health [GM021342]; National Institutes of Health, National Heart, Lung and Blood Institute FX This work was supported in part by the National Science Foundation (MCB-0918374 to W.I.); TeraGrid resources were provided by Purdue University (National Science Foundation, OCI-0503992 to W.I.), the National Institutes of Health (GM021342 to O.S.A.), and the Intramural Research Program of the National Institutes of Health, National Heart, Lung and Blood Institute (to R.W.P.). NR 57 TC 47 Z9 47 U1 4 U2 37 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 APR 4 PY 2012 VL 102 IS 7 BP 1551 EP 1560 DI 10.1016/j.bpj.2012.03.014 PG 10 WC Biophysics SC Biophysics GA 920XR UT WOS:000302443100010 PM 22500755 ER PT J AU Mazumder, A Bandyopadhyay, S Dhar, A Lewis, DEA Deb, S Dey, S Chakrabarti, P Roy, S AF Mazumder, Abhishek Bandyopadhyay, Sumita Dhar, Amlanjyoti Lewis, Dale E. A. Deb, Sunanda Dey, Sucharita Chakrabarti, Pinak Roy, Siddhartha TI A Genetic Network That Balances Two Outcomes Utilizes Asymmetric Recognition of Operator Sites SO BIOPHYSICAL JOURNAL LA English DT Article ID LAMBDA-CI-REPRESSOR; BACTERIOPHAGE-LAMBDA; CONFORMATIONAL-CHANGES; TERMINAL DOMAIN; O-R; DNA; BINDING; TRANSCRIPTION; ENERGETICS; COLI AB Stability and induction of the lysogenic state of bacteriophage A are balanced by a complex regulatory network. A key feature of this network is the mutually exclusive cooperative binding of a repressor dimer (Cl) to one of two pairs of binding sites, O(R)1-O(R)2 or O(R)2-O(R)3. The structural features that underpin the mutually exclusive binding mode are not well understood. Recent studies have demonstrated that Cl is an asymmetric dimer. The functional importance of the asymmetry is not fully clear. Due to the asymmetric nature of the Cl dimer as well as its binding sites, there are two possible bound orientations. By fluorescence resonance energy transfer measurements we showed that Cl prefers one bound orientation. We also demonstrated that the relative configuration of the binding sites is important for Cl dimer-dimer interactions and consequent cooperative binding. We proposed that the operator configuration dictates the orientations of the bound Cl molecules, which in turn dictates Cl cooperative interaction between the O(R)1-O(R)2 or O(R)2-O(R)3, but not both. Modeling suggests that the relative orientation of the C- and N-terminal domains may play an important role in the mutually exclusive nature of the cooperative binding. This work correlates unique structural features of a transcription regulatory protein with the functional properties of a gene regulatory network. C1 [Mazumder, Abhishek; Roy, Siddhartha] Indian Inst Chem Biol, Council Sci & Ind Res, Div Struct Biol & Bioinformat, Kolkata 700032, W Bengal, India. [Dey, Sucharita; Chakrabarti, Pinak] Bose Inst, Dept Biochem, Kolkata 700009, W Bengal, India. [Bandyopadhyay, Sumita; Deb, Sunanda] Bose Inst, Dept Biophys, Kolkata 700009, W Bengal, India. [Dhar, Amlanjyoti; Lewis, Dale E. A.] NCI, Mol Biol Lab, Bethesda, MD 20892 USA. RP Roy, S (reprint author), Indian Inst Chem Biol, Council Sci & Ind Res, Div Struct Biol & Bioinformat, 4 Raja Sc Mullick Rd, Kolkata 700032, W Bengal, India. EM sidroykolkata@gmail.com FU Department of Science and Technology, Government of India; Council of Scientific and Industrial Research; National Institutes of Health; National Cancer Institute; Center for Cancer Research FX We acknowledge the Department of Science and Technology, Government of India, for JC Bose Fellowship to SR., Council of Scientific and Industrial Research for funding the work and fellowship to A.M. This work was also supported by the Intramural Research Program of the National Institutes of Health, the National Cancer Institute, and the Center for Cancer Research. NR 29 TC 0 Z9 0 U1 0 U2 5 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 0006-3495 EI 1542-0086 J9 BIOPHYS J JI Biophys. J. PD APR 4 PY 2012 VL 102 IS 7 BP 1580 EP 1589 DI 10.1016/j.bpj.2012.01.052 PG 10 WC Biophysics SC Biophysics GA 920XR UT WOS:000302443100013 PM 22500758 ER PT J AU Mueller, F Morisaki, T Mazza, D McNally, JG AF Mueller, Florian Morisaki, Tatsuya Mazza, Davide McNally, James G. TI Minimizing the Impact of Photoswitching of Fluorescent Proteins on FRAP Analysis SO BIOPHYSICAL JOURNAL LA English DT Article ID NUCLEAR PROTEINS; HUMAN-CELLS; CHROMATIN; RECOVERY; DYNAMICS; BINDING; DIFFUSION; MOLECULES; MOBILITY AB Fluorescence recovery after photobleaching (FRAP) is a widely used imaging technique for measuring the mobility of fluorescently tagged proteins in living cells. Although FRAP presumes that high-intensity illumination causes only irreversible. photobleaching, reversible photoswitching of many fluorescent molecules, including GFP, can also occur. Here, we show that this photoswitching is likely to contaminate many FRAPs of GFP, and worse, the size of its contribution can be up to 60% under different experimental conditions, making it difficult to compare FRAPs from different studies. We develop a procedure to correct FRAPs for photoswitching and apply it to FRAPs of the GFP-tagged histone H2B, which, depending on the precise photobleaching conditions exhibits apparent fast components ranging from 9-36% before correction and similar to 1% after correction. We demonstrate how this similar to 1% fast component of H28-GFP can be used as a benchmark both to estimate the role of photoswitching in previous FRAP studies of TATA binding proteins (TBP) and also as a tool to minimize the contribution of photoswitching to tolerable levels in future FRAP experiments. In sum, we show how the impact of photoswitching on FRAP can be identified, minimized, and corrected. C1 [Mueller, Florian; Morisaki, Tatsuya; Mazza, Davide; McNally, James G.] NCI, Lab Receptor Biol & Gene Express, Bethesda, MD 20892 USA. RP McNally, JG (reprint author), NCI, Lab Receptor Biol & Gene Express, Bethesda, MD 20892 USA. EM mcnallyj@exchange.nih.gov RI Mueller, Florian/C-9075-2012; Mazza, Davide/R-5340-2016 OI Mueller, Florian/0000-0002-9622-4396; Mazza, Davide/0000-0003-2776-4142 FU National Institutes of Health, National Cancer Institute, Center for Cancer Research FX This research was supported in part by the intramural program of the National Institutes of Health, National Cancer Institute, Center for Cancer Research. NR 21 TC 23 Z9 23 U1 1 U2 9 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 APR 4 PY 2012 VL 102 IS 7 BP 1656 EP 1665 DI 10.1016/j.bpj.2012.02.029 PG 10 WC Biophysics SC Biophysics GA 920XR UT WOS:000302443100021 PM 22500766 ER PT J AU Ulrich, CM Grady, C AF Ulrich, Connie M. Grady, Christine TI Perceptions of Appropriateness of Care in the Intensive Care Unit SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Letter ID ETHICS CONSULTATION C1 [Ulrich, Connie M.] Univ Penn, Sch Nursing, Dept Med Eth & Hlth Policy, Philadelphia, PA 19104 USA. [Grady, Christine] NIH, Dept Bioeth, Ctr Clin, Bethesda, MD 20892 USA. RP Ulrich, CM (reprint author), Univ Penn, Sch Nursing, Dept Med Eth & Hlth Policy, Philadelphia, PA 19104 USA. EM culrich@nursing.upenn.edu FU Intramural NIH HHS [Z99 CL999999] NR 3 TC 0 Z9 0 U1 1 U2 3 PU AMER MEDICAL ASSOC PI CHICAGO PA 330 N WABASH AVE, STE 39300, CHICAGO, IL 60611-5885 USA SN 0098-7484 EI 1538-3598 J9 JAMA-J AM MED ASSOC JI JAMA-J. Am. Med. Assoc. PD APR 4 PY 2012 VL 307 IS 13 BP 1370 EP 1371 DI 10.1001/jama.2012.394 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA 919AY UT WOS:000302294200015 PM 22474196 ER PT J AU Alberts, SR Sargent, DJ Nair, S Mahoney, MR Mooney, M Thibodeau, SN Smyrk, TC Sinicrope, FA Chan, E Gill, S Kahlenberg, MS Shields, AF Quesenberry, JT Webb, TA Farr, GH Pockaj, BA Grothey, A Goldberg, RM AF Alberts, Steven R. Sargent, Daniel J. Nair, Suresh Mahoney, Michelle R. Mooney, Margaret Thibodeau, Stephen N. Smyrk, Thomas C. Sinicrope, Frank A. Chan, Emily Gill, Sharlene Kahlenberg, Morton S. Shields, Anthony F. Quesenberry, James T. Webb, Thomas A. Farr, Gist H., Jr. Pockaj, Barbara A. Grothey, Axel Goldberg, Richard M. TI Effect of Oxaliplatin, Fluorouracil, and Leucovorin With or Without Cetuximab on Survival Among Patients With Resected Stage III Colon Cancer A Randomized Trial SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Article ID METASTATIC COLORECTAL-CANCER; EPITHELIAL-MESENCHYMAL TRANSITION; MRC COIN TRIAL; 1ST-LINE TREATMENT; ADJUVANT TREATMENT; PHASE-III; CHEMOTHERAPY; PANITUMUMAB; FLUOROPYRIMIDINE; IRINOTECAN AB Context Leucovorin, fluorouracil, and oxaliplatin (FOLFOX) is the standard adjuvant therapy for resected stage III colon cancer. Adding cetuximab to FOLFOX benefits patients with metastatic wild-type KRAS but not mutated KRAS colon cancer. Objective To assess the potential benefit of cetuximab added to the modified sixth version of the FOLFOX regimen (mFOLFOX6) in patients with resected stage III wild-type KRAS colon cancer. Design, Setting, and Participants A randomized trial of 2686 patients aged 18 years or older at multiple institutions across North America enrolled following resection and informed consent between February 10, 2004, and November 25, 2009. The primary randomized comparison was 12 biweekly cycles of mFOLFOX6 with and without cetuximab. KRAS mutation status was centrally determined. The trial was halted after a planned interim analysis of 48% of predicted events (246/515) occurring in 1863 (of 2070 planned) patients with tumors having wild-type KRAS. A total of 717 patients with mutated KRAS and 106 with indeterminate KRAS were accrued. The 2070 patients with wild-type KRAS provided 90% power to detect a hazard ratio (HR) of 1.33 (2-sided alpha=.05), with planned interim efficacy analyses after 25%, 50%, and 75% of expected relapses. Main Outcome Measures Disease-free survival in patients with wild-type KRAS mutations. Secondary end points included overall survival and toxicity. Results Median (range) follow-up was 28 (0-68) months. The trial demonstrated no benefit when adding cetuximab. Three-year disease-free survival for mFOLFOX6 alone was 74.6% vs 71.5% with the addition of cetuximab (HR, 1.21; 95% CI, 0.98-1.49; P=.08) in patients with wild-type KRAS, and 67.1% vs 65.0% (HR, 1.12; 95% CI, 0.86-1.46; P=.38) in patients with mutated KRAS, with no significant benefit in any subgroups assessed. Among all patients, grade 3 or higher adverse events (72.5% vs 52.3%; odds ratio [OR], 2.4; 95% CI, 2.1-2.8; P<.001) and failure to complete 12 cycles (33% vs 23%; OR, 1.6; 95% CI, 1.4-1.9; P<.001) were significantly higher with cetuximab. Increased toxicity and greater detrimental differences in all outcomes were observed in patients aged 70 years or older. Conclusion Among patients with stage III resected colon cancer, the use of cetuximab with adjuvant mFOLFOX6 compared with mFOLFOX6 alone did not result in improved disease-free survival. C1 [Alberts, Steven R.; Sinicrope, Frank A.; Grothey, Axel] Mayo Clin, Dept Oncol, Rochester, MN 55905 USA. [Sargent, Daniel J.; Mooney, Margaret] Mayo Clin, Dept Hlth Sci Res, Rochester, MN USA. Mayo Clin, Dept Hlth Sci Res, Rochester, MN USA. [Nair, Suresh] Lehigh Valley Hosp, Allentown, PA USA. [Mooney, Margaret] NCI, Clin Invest Branch, Canc Therapy Evaluat Program, Bethesda, MD 20892 USA. [Chan, Emily] Vanderbilt Univ, Med Ctr, Nashville, TN USA. [Gill, Sharlene] British Columbia Canc Agcy, Vancouver, BC V5Z 4E6, Canada. [Kahlenberg, Morton S.] Surg Oncol Associates S Texas, San Antonio, TX USA. [Shields, Anthony F.] Karmanos Canc Inst, Detroit, MI USA. [Quesenberry, James T.] Siouxland Hematol Oncol Associates, Sioux City, IA USA. [Webb, Thomas A.] Illinois Oncol Res Assoc, Community Clin Oncol Program, Peoria, IL USA. [Farr, Gist H., Jr.] Ochsner Community Clin Oncol Program, New Orleans, LA USA. [Goldberg, Richard M.] Ohio State Univ, Columbus, OH 43210 USA. RP Alberts, SR (reprint author), Mayo Clin, Dept Oncol, Rochester, MN 55905 USA. RI Goldberg , Richard/M-1311-2013; OI Sargent, Daniel/0000-0002-2684-4741 FU National Cancer Institute, Department of Health and Human Services [CA-25224, CA-37404, CA-35103, CA-35113, CA-35272, CA-114740, CA-32102, CA-14028, CA49957, CA21115, CA31946, CA12027, CA37377]; Bristol-Myers Squibb; ImClone; sanofi-aventis; Pfizer; sanofi-aventis by the North Central Cancer Treatment Group (NCCTG); Merck Serono; Eastern Cooperative Oncology Group; National Comprehensive Cancer Network; Genentech; Southwest Oncology Group FX All authors have completed and submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Dr Alberts reported receiving grants from Pfizer, Bristol-Myers Squibb, and sanofi-aventis by the North Central Cancer Treatment Group (NCCTG) for support of the conduct of this trial. Dr Sargent reported receiving grants from Pfizer, Bristol-Myers Squibb, and sanofi-aventis for support to NCCTG for conduct of this trial. Dr Nair reported receiving support for travel to meetings from National Cancer Institute Cooperative Group. Dr Sinicrope reported receiving consultancy fees from Merck Serono, receiving grants from the National Institutes of Health, payment for lectures including service on service bureaus from the University of Kansas, and travel meeting expenses from the American Society of Clinical Oncology. Dr Chan reported receiving a grant from the Eastern Cooperative Oncology Group; being a board member of Colorectal Cancer Index and Reviews and HCPLive.com Oncology Advisory Board; being a consultant on advisory boards of Amgen, ImClone, Bristol-Myers Squibb, Genentech, Pfizer, and Celgene; receiving grants and travel meeting expenses from National Comprehensive Cancer Network; receiving travel meeting expenses from Chemotherapy Foundation; and being an institutional investigator in numerous clinical trials involving multiple pharmaceutical companies. Dr Gill reported receiving payment for lectures including service on speakers bureaus from Bristol-Myers Squibb. Dr Kahlenberg reported receiving payment for lectures including service on speakers bureaus from Genentech. Dr Shields reported receiving grant and support for travel to meetings for the study from Southwest Oncology Group. Dr Grothey reported receiving grants and consultancy fees from sanofi-aventis. No other authors provided any financial disclosures.; This trial was conducted as a collaborative trial of the North Central Cancer Treatment Group (NCCTG), Mayo Clinic, and was supported in part by Public Health Service grants CA-25224, CA-37404, CA-35103, CA-35113, CA-35272, CA-114740, CA-32102, CA-14028, CA49957, CA21115, CA31946, CA12027, CA37377 from the National Cancer Institute, Department of Health and Human Services. Bristol-Myers Squibb, ImClone, sanofi-aventis, and Pfizer provided unrestricted support to NCCTG for conduct of trial. Bristol-Myers Squibb provided cetuximab to NCCTG. NR 33 TC 172 Z9 176 U1 1 U2 11 PU AMER MEDICAL ASSOC PI CHICAGO PA 330 N WABASH AVE, STE 39300, CHICAGO, IL 60611-5885 USA SN 0098-7484 EI 1538-3598 J9 JAMA-J AM MED ASSOC JI JAMA-J. Am. Med. Assoc. PD APR 4 PY 2012 VL 307 IS 13 BP 1383 EP 1393 DI 10.1001/jama.2012.385 PG 11 WC Medicine, General & Internal SC General & Internal Medicine GA 919AY UT WOS:000302294200025 PM 22474202 ER PT J AU Millum, J AF Millum, Joseph TI Canada's new ethical guidelines for research with humans: a critique and comparison with the United States SO CANADIAN MEDICAL ASSOCIATION JOURNAL LA English DT Article ID BOARD; MULTICENTER C1 [Millum, Joseph] NIH, Dept Bioeth, Bethesda, MD 20892 USA. [Millum, Joseph] NIH, Fogarty Int Ctr, Bethesda, MD 20892 USA. RP Millum, J (reprint author), NIH, Dept Bioeth, Bldg 10, Bethesda, MD 20892 USA. EM millumj@cc.nih.gov NR 24 TC 1 Z9 1 U1 1 U2 3 PU CMA-CANADIAN MEDICAL ASSOC PI OTTAWA PA 1867 ALTA VISTA DR, OTTAWA, ONTARIO K1G 5W8, CANADA SN 0820-3946 J9 CAN MED ASSOC J JI Can. Med. Assoc. J. PD APR 3 PY 2012 VL 184 IS 6 BP 657 EP 661 DI 10.1503/cmaj.111217 PG 5 WC Medicine, General & Internal SC General & Internal Medicine GA 007NJ UT WOS:000308894700033 PM 22249987 ER PT J AU Moon, AF Xu, YM Woody, SM Krahn, JM Linhardt, RJ Liu, J Pedersen, LC AF Moon, Andrea F. Xu, Yongmei Woody, Susan M. Krahn, Joseph M. Linhardt, Robert J. Liu, Jian Pedersen, Lars C. TI Dissecting the substrate recognition of 3-O-sulfotransferase for the biosynthesis of anticoagulant heparin SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE oligosaccharides; substrate specificity; ternary complex; heparan sulfate ID SULFATE; ANTITHROMBIN; CONFORMER; RESIDUES; BINDING; ENTRY AB Heparin is a polysaccharide-based natural product that is used clinically as an anticoagulant drug. Heparan sulfate 3-O-sulfotransferase (3-OST) is an enzyme that transfers a sulfo group to the 3-OH position of a glucosamine unit. 3-OST is present in multiple isoforms, and the polysaccharides modified by these different isoforms perform distinct biological functions. 3-OST isoform 1 (3-OST-1) is the key enzyme for the biosynthesis of anticoagulant heparin. Here, we report the crystal structure of the ternary complex of 3-OST-1, 3'-phosphoadenosine 5'-phosphate, and a heptasaccharide substrate. Comparisons to previously determined structures of 3-OST-3 reveal unique binding modes used by the different isoforms of 3-OST for distinguishing the fine structures of saccharide substrates. Our data demonstrate that the saccharide substrates display distinct conformations when interacting with the different 3-OST isoforms. Site-directed mutagenesis data suggest that several key amino residues, including Lys259, Thr256, and Trp283 in 3-OST-3 and Arg268 in 3-OST-1, play important roles in substrate binding and specificity between isoforms. These results deepen our understanding of the biosynthetic mechanism of heparan sulfate and provide structural information for engineering enzymes for an enhanced biosynthetic approach to heparin production. C1 [Xu, Yongmei; Woody, Susan M.; Liu, Jian] Univ N Carolina, Div Chem Biol & Med Chem, Eshelman Sch Pharm, Chapel Hill, NC 27599 USA. [Moon, Andrea F.; Krahn, Joseph M.; Pedersen, Lars C.] NIEHS, Struct Biol Lab, NIH, Res Triangle Pk, NC 27709 USA. [Linhardt, Robert J.] Rensselaer Polytech Inst, Ctr Biotechnol & Interdisciplinary Studies, Dept Chem & Chem Biol, Troy, NY 12180 USA. RP Liu, J (reprint author), Univ N Carolina, Div Chem Biol & Med Chem, Eshelman Sch Pharm, Chapel Hill, NC 27599 USA. EM jian_liu@unc.edu FU Division of Intramural Research of the National Institute of Environmental Health Sciences, National Institutes of Health (NIH) [1 ZIA ES102645-03]; NIH [AI050050, HL094463, HL096972]; US Department of Energy, Office of Science, Office of Basic Energy Sciences [W-31-109-Eng-38] FX We thank G. Mueller and S. Garantziotis for critical reading of the manuscript, and Prof. Peng George Wang (Georgia State University) for providing the plasmid expressing NAHK. This research was supported by the Division of Intramural Research of the National Institute of Environmental Health Sciences, National Institutes of Health (NIH) Grant 1 ZIA ES102645-03; and NIH Grants AI050050, HL094463, and HL096972. Use of the Advanced Photon Source was supported by the US Department of Energy, Office of Science, Office of Basic Energy Sciences Contract W-31-109-Eng-38. NR 19 TC 28 Z9 28 U1 1 U2 19 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD APR 3 PY 2012 VL 109 IS 14 BP 5265 EP 5270 DI 10.1073/pnas.1117923109 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 919BD UT WOS:000302294700037 PM 22431632 ER PT J AU Zhao, J Jitkaew, S Cai, ZY Choksi, S Li, QN Luo, J Liu, ZG AF Zhao, Jie Jitkaew, Siriporn Cai, Zhenyu Choksi, Swati Li, Qiuning Luo, Ji Liu, Zheng-Gang TI Mixed lineage kinase domain-like is a key receptor interacting protein 3 downstream component of TNF-induced necrosis SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID NONAPOPTOTIC CELL-DEATH; NF-KAPPA-B; PROGRAMMED NECROSIS; ACTIVATION; APOPTOSIS; PATHWAY; ACCUMULATION; INDUCTION; ALPHA; JNK AB Tumor necrosis factor (TNF) is an important inflammatory cytokine and induces many cellular responses, including inflammation, cell proliferation, apoptosis, and necrosis. It is known that receptor interacting protein (RIP) kinases, RIP1 and RIP3, are key effectors of TNF-induced necrosis, but little is known about how these two RIP kinases mediate this process, although reactive oxygen species (ROS) generation and JNK activation have been suggested to be two downstream events of RIP kinases. Here we report the identification of mixed lineage kinase domain-like, MLKL, as a key RIP3 downstream component of TNF-induced necrosis. Through screening a kinase/phosphatase shRNA library in human colon adenocarcinoma HT-29 cells, we found that knockdown of MLKL blocked TNF-induced necrosis. Our data suggest that MLKL functions downstream of RIP1 and RIP3 and is recruited to the necrosome through its interaction with RIP3. Finally, we found that MLKL is required for the generation of ROS and the late-phase activation of JNK during TNF-induced necrosis. However, because these two events are not involved in TNF-induced necrosis in HT-29 cells, the target of MLKL during TNF-induced necrosis remains elusive. Taken together, our study suggests that MLKL is a key RIP3 downstream component of TNF-induced necrotic cell death. C1 [Zhao, Jie; Jitkaew, Siriporn; Cai, Zhenyu; Choksi, Swati; Liu, Zheng-Gang] NCI, Cell & Canc Biol Branch, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. [Li, Qiuning; Luo, Ji] NCI, Med Oncol Branch, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. RP Liu, ZG (reprint author), NCI, Cell & Canc Biol Branch, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. EM zgliu@box-z.nih.gov FU Center for Cancer Research, National Cancer Institute, National Institutes of Health FX We thank Drs. Francis Ka Ming Chan and Jiahuai Han for the RIP3 plasmids. This research was supported by the Intramural Research Program of the Center for Cancer Research, National Cancer Institute, National Institutes of Health. NR 28 TC 218 Z9 224 U1 0 U2 18 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD APR 3 PY 2012 VL 109 IS 14 BP 5322 EP 5327 DI 10.1073/pnas.1200012109 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 919BD UT WOS:000302294700047 PM 22421439 ER PT J AU Fox, JT Sakamuru, S Huang, RL Teneva, N Simmons, SO Xia, MH Tice, RR Austin, CP Myung, K AF Fox, Jennifer T. Sakamuru, Srilatha Huang, Ruili Teneva, Nedelina Simmons, Steven O. Xia, Menghang Tice, Raymond R. Austin, Christopher P. Myung, Kyungjae TI High-throughput genotoxicity assay identifies antioxidants as inducers of DNA damage response and cell death SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE chemotherapy; high-throughput screening ID POSTMENOPAUSAL WOMEN; PHYTOESTROGEN GENISTEIN; XERODERMA-PIGMENTOSUM; CHEMICAL LIBRARIES; POLYMERASE ETA; CANCER CELLS; HUMAN ELG1; NUDE-MICE; IN-VIVO; RESVERATROL AB Human ATAD5 is a biomarker for identifying genotoxic compounds because ATAD5 protein levels increase posttranscriptionally in response to DNA damage. We screened over 4,000 compounds with a cell-based quantitative high-throughput ATAD5-luciferase assay detecting genotoxic compounds. We identified 22 antioxidants, including resveratrol, genistein, and baicalein, that are currently used or investigated for the treatment of cardiovascular disease, type 2 diabetes, osteopenia, osteoporosis, and chronic hepatitis, as well as for antiaging. Treatment of dividing cells with these compounds induced DNA damage and resulted in cell death. Despite their genotoxic effects, resveratrol, genistein, and baicalein did not cause mutagenesis, which is a major side effect of conventional anticancer drugs. Furthermore, resveratrol and genistein killed multidrug-resistant cancer cells. We therefore propose that resveratrol, genistein, and baicalein are attractive candidates for improved chemotherapeutic agents. C1 [Fox, Jennifer T.; Teneva, Nedelina; Myung, Kyungjae] NHGRI, Genome Instabil Sect, Genet & Mol Biol Branch, Bethesda, MD 20892 USA. [Sakamuru, Srilatha; Huang, Ruili; Xia, Menghang; Austin, Christopher P.] NIH, Natl Ctr Adv Translat Sci, Bethesda, MD 20892 USA. [Simmons, Steven O.] US EPA, Integrated Syst Toxicol Div, Natl Hlth & Environm Effects Res Lab, Res Triangle Pk, NC 27711 USA. [Tice, Raymond R.] NIEHS, Div Natl Toxicol Program, NIH, Res Triangle Pk, NC 27709 USA. RP Myung, K (reprint author), NHGRI, Genome Instabil Sect, Genet & Mol Biol Branch, Bethesda, MD 20892 USA. EM kmyung@mail.nih.gov OI Simmons, Steven/0000-0001-9079-1069 FU National Institute of Environmental Health Sciences [Y2-ES-7020-01]; National Human Genome Research Institute, National Institutes of Health; [R03 MH092164-01] FX We thank S. Anderson in the FACS core, A. Dutra in the cytogenetics core, and D. Bodine, F. Candotti, P. Schwartzberg, and Y. Yang of the National Human Genome Research Institute for helpful discussions and comments on the manuscript; M. Gottesman and C. Cardarelli of the National Cancer Institute for cell lines; and K.M. especially thanks E. Cho. This research was supported by the Intramural Research Programs (Interagency Agreement Y2-ES-7020-01) of the National Toxicology Program, National Institute of Environmental Health Sciences, and the National Human Genome Research Institute, National Institutes of Health, and by Grant R03 MH092164-01 (to K.M and M.X.). NR 36 TC 46 Z9 47 U1 5 U2 26 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD APR 3 PY 2012 VL 109 IS 14 BP 5423 EP 5428 DI 10.1073/pnas.1114278109 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 919BD UT WOS:000302294700064 PM 22431602 ER PT J AU Waisberg, M Cerqueira, GC Yager, SB Francischetti, IMB Lu, JH Gera, N Srinivasan, P Miura, K Rada, B Lukszo, J Barbian, KD Leto, TL Porcella, SF Narum, DL El-Sayed, N Miller, LH Pierce, SK AF Waisberg, Michael Cerqueira, Gustavo C. Yager, Stephanie B. Francischetti, Ivo M. B. Lu, Jinghua Gera, Nidhi Srinivasan, Prakash Miura, Kazutoyo Rada, Balazs Lukszo, Jan Barbian, Kent D. Leto, Thomas L. Porcella, Stephen F. Narum, David L. El-Sayed, Najib Miller, Louis H. Pierce, Susan K. TI Plasmodium falciparum merozoite surface protein 1 blocks the proinflammatory protein S100P SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE placental; yeast two-hybrid; surface plasmon resonance; high-throughput screen ID MALARIA PARASITE; CELL INVASION; IMMUNITY; ANTIBODIES; HEMOZOIN; DISEASE; VACCINE; FAMILY; DNA AB The malaria parasite, Plasmodium falciparum, and the human immune system have coevolved to ensure that the parasite is not eliminated and reinfection is not resisted. This relationship is likely mediated through a myriad of host-parasite interactions, although surprisingly few such interactions have been identified. Here we show that the 33-kDa fragment of P. falciparum merozoite surface protein 1 (MSP1(33)), an abundant protein that is shed during red blood cell invasion, binds to the proinflammatory protein, S100P. MSP1(33) blocks S100P-induced NF kappa B activation in monocytes and chemotaxis in neutrophils. Remarkably, S100P binds to both dimorphic alleles of MSP1, estimated to have diverged >27 Mya, suggesting an ancient, conserved relationship between these parasite and host proteins that may serve to attenuate potentially damaging inflammatory responses. C1 [Waisberg, Michael; Yager, Stephanie B.; Lu, Jinghua; Gera, Nidhi; Pierce, Susan K.] NIAID, Immunogenet Lab, NIH, Rockville, MD 20852 USA. [Rada, Balazs; Leto, Thomas L.] NIAID, Host Def Lab, NIH, Rockville, MD 20852 USA. [Francischetti, Ivo M. B.; Srinivasan, Prakash; Miura, Kazutoyo; Miller, Louis H.] NIAID, Lab Malaria & Vector Res, NIH, Rockville, MD 20852 USA. [Lukszo, Jan; Barbian, Kent D.; Porcella, Stephen F.] NIAID, Res Technol Branch, NIH, Rockville, MD 20852 USA. [Narum, David L.] NIAID, Lab Malaria Immunol & Vaccinol, NIH, Rockville, MD 20852 USA. [Cerqueira, Gustavo C.; El-Sayed, Najib] Univ Maryland, Maryland Pathogen Res Inst, College Pk, MD 20742 USA. RP Waisberg, M (reprint author), NIAID, Immunogenet Lab, NIH, Rockville, MD 20852 USA. EM waisbergm@niaid.nih.gov; lmiller@niaid.nih.gov RI lu, jinghua/G-5872-2012; El-Sayed, Najib/K-7266-2015 OI El-Sayed, Najib/0000-0001-7970-3312 FU National Institutes of Health, National Institute of Allergy and Infectious Diseases FX The authors thank Dr. George Makhatadze for sharing reagents, Ms. Julie Kim for logistic support, and Ms. Terri Fantasia for editorial support. This study was supported by the Intramural Research Program of the National Institutes of Health, National Institute of Allergy and Infectious Diseases. NR 31 TC 8 Z9 8 U1 0 U2 1 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD APR 3 PY 2012 VL 109 IS 14 BP 5429 EP 5434 DI 10.1073/pnas.1202689109 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 919BD UT WOS:000302294700065 PM 22431641 ER PT J AU Veenstra-VanderWeele, J Muller, CL Iwamoto, H Sauer, JE Owens, WA Shah, CR Cohen, J Mannangatti, P Jessen, T Thompson, BJ Ye, R Kerr, TM Carneiro, AM Crawley, JN Sanders-Bush, E McMahon, DG Ramamoorthy, S Daws, LC Sutcliffe, JS Blakely, RD AF Veenstra-VanderWeele, Jeremy Muller, Christopher L. Iwamoto, Hideki Sauer, Jennifer E. Owens, W. Anthony Shah, Charisma R. Cohen, Jordan Mannangatti, Padmanabhan Jessen, Tammy Thompson, Brent J. Ye, Ran Kerr, Travis M. Carneiro, Ana M. Crawley, Jacqueline N. Sanders-Bush, Elaine McMahon, Douglas G. Ramamoorthy, Sammanda Daws, Lynette C. Sutcliffe, James S. Blakely, Randy D. TI Autism gene variant causes hyperserotonemia, serotonin receptor hypersensitivity, social impairment and repetitive behavior SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE development; monoamine; neurotransmitter ID ACTIVATED PROTEIN-KINASE; WHOLE-BLOOD SEROTONIN; SPECTRUM DISORDERS; MOUSE MODEL; IN-VIVO; TRANSPORTER; MICE; EXPRESSION; PHOSPHORYLATION; ABNORMALITIES AB Fifty years ago, increased whole-blood serotonin levels, or hyperserotonemia, first linked disrupted 5-HT homeostasis to Autism Spectrum Disorders (ASDs). The 5-HT transporter (SERT) gene (SLC6A4) has been associated with whole blood 5-HT levels and ASD susceptibility. Previously, we identified multiple gain-of-function SERT coding variants in children with ASD. Here we establish that transgenic mice expressing the most common of these variants, SERT Ala56, exhibit elevated, p38 MAPK-dependent transporter phosphorylation, enhanced 5-HT clearance rates and hyperserotonemia. These effects are accompanied by altered basal firing of raphe 5-HT neurons, as well as 5HT(1A) and 5HT(2A) receptor hypersensitivity. Strikingly, SERT Ala56 mice display alterations in social function, communication, and repetitive behavior. Our efforts provide strong support for the hypothesis that altered 5-HT homeostasis can impact risk for ASD traits and provide a model with construct and face validity that can support further analysis of ASD mechanisms and potentially novel treatments. C1 [Veenstra-VanderWeele, Jeremy; Muller, Christopher L.; Sauer, Jennifer E.; Shah, Charisma R.; Cohen, Jordan; Sanders-Bush, Elaine; Sutcliffe, James S.; Blakely, Randy D.] Vanderbilt Univ, Dept Psychiat, Nashville, TN 37232 USA. [Veenstra-VanderWeele, Jeremy] Vanderbilt Univ, Dept Pediat, Nashville, TN 37232 USA. [Veenstra-VanderWeele, Jeremy; Iwamoto, Hideki; Jessen, Tammy; Ye, Ran; Kerr, Travis M.; Carneiro, Ana M.; Sanders-Bush, Elaine; McMahon, Douglas G.; Blakely, Randy D.] Vanderbilt Univ, Dept Pharmacol, Nashville, TN 37232 USA. [Veenstra-VanderWeele, Jeremy; Carneiro, Ana M.; Sanders-Bush, Elaine; McMahon, Douglas G.; Sutcliffe, James S.; Blakely, Randy D.] Vanderbilt Univ, Inst Brain, Nashville, TN 37232 USA. [Veenstra-VanderWeele, Jeremy; Carneiro, Ana M.; Sanders-Bush, Elaine; McMahon, Douglas G.; Sutcliffe, James S.; Blakely, Randy D.] Vanderbilt Univ, Kennedy Ctr Res Human Dev, Nashville, TN 37232 USA. [Owens, W. Anthony; Daws, Lynette C.] Univ Texas Hlth Sci Ctr San Antonio, Dept Physiol, San Antonio, TX 78229 USA. [Mannangatti, Padmanabhan; Ramamoorthy, Sammanda] Univ Texas Hlth Sci Ctr San Antonio, Dept Neurosci, San Antonio, TX 78229 USA. [Thompson, Brent J.] Univ Texas Hlth Sci Ctr San Antonio, Dept Cellular & Struct Biol, San Antonio, TX 78229 USA. [Thompson, Brent J.; Daws, Lynette C.] Univ Texas Hlth Sci Ctr San Antonio, Dept Pharmacol, San Antonio, TX 78229 USA. [Crawley, Jacqueline N.] NIMH, Lab Behav Neurosci, Bethesda, MD 20892 USA. [Sanders-Bush, Elaine; McMahon, Douglas G.; Blakely, Randy D.] Vanderbilt Univ, Silvio O Conte Ctr Neurosci Res, Nashville, TN 37232 USA. [McMahon, Douglas G.] Vanderbilt Univ, Dept Biol Sci, Nashville, TN 37232 USA. [Sutcliffe, James S.] Vanderbilt Univ, Dept Mol Physiol & Biophys, Nashville, TN 37232 USA. RP Veenstra-VanderWeele, J (reprint author), Vanderbilt Univ, Dept Psychiat, 221 Kirkland Hall, Nashville, TN 37232 USA. EM j.vvw@vanderbilt.edu; randy.blakely@vanderbilt.edu RI Sutcliffe, James/C-1348-2012; Thompson, Brent/L-1336-2014; Veenstra-VanderWeele, Jeremy/K-1935-2015 OI Sutcliffe, James/0000-0001-5200-6007; Thompson, Brent/0000-0002-2302-0886; Veenstra-VanderWeele, Jeremy/0000-0002-6349-1076 FU National Institutes of Health (NIH) [MH081066, MH094604, DA07390, MH078098, HD065278, MH62612, HD15052, RR024975]; Autism Speaks Pilot Award; American Academy of Child and Adolescent Psychiatry; Seaside Therapeutics; Roche Pharmaceuticals; Novartis; Forest Pharmaceuticals FX Michelle Carter, Lauren Huntress, and Clinton Canal provided technical assistance; Mu Yang and Jill Silverman provided advice on behavioral data analysis; and Warren Lambert provided statistical assistance. The authors thank the families who participated in the original genetic study. This work was supported by National Institutes of Health (NIH) Grants MH081066 (to J.V.), MH094604 (to J.V.), DA07390 (to R.D.B.), MH078098 (to R.D.B.), HD065278 (to R.D.B.), and MH62612 (to S.R.); an Autism Speaks Pilot Award (to J.V.), an American Academy of Child and Adolescent Psychiatry Pilot Research Award (to J.V.), and NIH Grants HD15052 (to the Vanderbilt Kennedy Center) and RR024975 (to the Vanderbilt Institute for Clinical and Translational Research).; The authors have no direct competing financial interests. J.V. receives research funding for nonoverlapping work from Seaside Therapeutics, Roche Pharmaceuticals, and Novartis, and has served as a consultant to Novartis. R.D.B. receives research funding for nonoverlapping work from Forest Pharmaceuticals and serves on the Lundbeck Pharmaceuticals Advisory Board and as a consultant to JubilantInnovation. NR 62 TC 103 Z9 103 U1 0 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 APR 3 PY 2012 VL 109 IS 14 BP 5469 EP 5474 DI 10.1073/pnas.1112345109 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 919BD UT WOS:000302294700072 PM 22431635 ER PT J AU Gonzalez-Castillo, J Saad, ZS Handwerker, DA Inati, SJ Brenowitz, N Bandettini, PA AF Gonzalez-Castillo, Javier Saad, Ziad S. Handwerker, Daniel A. Inati, Souheil J. Brenowitz, Noah Bandettini, Peter A. TI Whole-brain, time-locked activation with simple tasks revealed using massive averaging and model-free analysis SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE fMRI; activation extent; transient responses; clustering ID BOLD HEMODYNAMIC-RESPONSES; FUNCTIONAL CONNECTIVITY; NEURONAL-ACTIVITY; SPATIAL EXTENT; FMRI DATA; TRANSIENT; MRI; IDENTIFICATION; NETWORKS; SIGNALS AB The brain is the body's largest energy consumer, even in the absence of demanding tasks. Electrophysiologists report on-going neuronal firing during stimulation or task in regions beyond those of primary relationship to the perturbation. Although the biological origin of consciousness remains elusive, it is argued that it emerges from complex, continuous whole-brain neuronal collaboration. Despite converging evidence suggesting the whole brain is continuously working and adapting to anticipate and actuate in response to the environment, over the last 20 y, task-based functional MRI (fMRI) have emphasized a localizationist view of brain function, with fMRI showing only a handful of activated regions in response to task/stimulation. Here, we challenge that view with evidence that under optimal noise conditions, fMRI activations extend well beyond areas of primary relationship to the task; and blood-oxygen level-dependent signal changes correlated with task-timing appear in over 95% of the brain for a simple visual stimulation plus attention control task. Moreover, we show that response shape varies substantially across regions, and that whole-brain parcellations based on those differences produce distributed clusters that are anatomically and functionally meaningful, symmetrical across hemispheres, and reproducible across subjects. These findings highlight the exquisite detail lying in fMRI signals beyond what is normally examined, and emphasize both the pervasiveness of false negatives, and how the sparseness of fMRI maps is not a result of localized brain function, but a consequence of high noise and overly strict predictive response models. C1 [Gonzalez-Castillo, Javier; Handwerker, Daniel A.; Brenowitz, Noah; Bandettini, Peter A.] NIMH, Sect Funct Imaging Methods, Lab Brain & Cognit, NIH, Bethesda, MD 20892 USA. [Inati, Souheil J.; Bandettini, Peter A.] NIMH, Funct MRI Facil, NIH, Bethesda, MD 20892 USA. RP Gonzalez-Castillo, J (reprint author), NIMH, Sect Funct Imaging Methods, Lab Brain & Cognit, NIH, Bethesda, MD 20892 USA. EM javier.gonzalez-castillo@nih.gov OI Gonzalez-Castillo, Javier/0000-0002-6520-5125 NR 39 TC 95 Z9 96 U1 0 U2 11 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD APR 3 PY 2012 VL 109 IS 14 BP 5487 EP 5492 DI 10.1073/pnas.1121049109 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 919BD UT WOS:000302294700075 PM 22431587 ER PT J AU Hartley, CA McKenna, MC Salman, R Holmes, A Casey, BJ Phelps, EA Glatt, CE AF Hartley, Catherine A. McKenna, Morgan C. Salman, Rabia Holmes, Andrew Casey, B. J. Phelps, Elizabeth A. Glatt, Charles E. TI Serotonin transporter polyadenylation polymorphism modulates the retention of fear extinction memory SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID GENETIC-VARIATION; DEPRESSION; ANXIETY; 5-HTTLPR; STRESS; METAANALYSIS; REGION; BRAIN; MICE; ABNORMALITIES AB Growing evidence suggests serotonin's role in anxiety and depression is mediated by its effects on learned fear associations. Pharmacological and genetic manipulations of serotonin signaling in mice alter the retention of fear extinction learning, which is inversely associated with anxious temperament in mice and humans. Here, we test whether genetic variation in serotonin signaling in the form of a common human serotonin transporter polyadenylation polymorphism (STPP/rs3813034) is associated with spontaneous fear recovery after extinction. We show that the risk allele of this polymorphism is associated with impaired retention of fear extinction memory and heightened anxiety and depressive symptoms. These STPP associations in humans mirror the phenotypic effects of serotonin transporter knockout in mice, highlighting the STPP as a potential genetic locus underlying interindividual differences in serotonin transporter function in humans. Furthermore, we show that the serotonin transporter polyadenylation profile associated with the STPP risk allele is altered through the chronic administration of fluoxetine, a treatment that also facilitates retention of extinction learning. The propensity to form persistent fear associations due to poor extinction recall may be an intermediate phenotype mediating the effects of genetic variation in serotonergic function on anxiety and depression. The consistency and specificity of these data across species provide robust support for this hypothesis and suggest that the little-studied STPP may be an important risk factor for mood and anxiety disorders in humans. C1 [Hartley, Catherine A.; Salman, Rabia; Phelps, Elizabeth A.] NYU, Dept Psychol, New York, NY 10003 USA. [Phelps, Elizabeth A.] NYU, Ctr Neural Sci, New York, NY 10003 USA. [McKenna, Morgan C.; Glatt, Charles E.] Weill Cornell Med Coll, Dept Psychiat, New York, NY 10065 USA. [Casey, B. J.] Weill Cornell Med Coll, Sackler Inst Dev Psychobiol, New York, NY 10065 USA. [Holmes, Andrew] NIAAA, Lab Behav & Genom Neurosci, Rockville, MD 20852 USA. RP Hartley, CA (reprint author), NYU, Dept Psychol, 6 Washington Pl, New York, NY 10003 USA. EM cate@nyu.edu; ceg2004@med.cornell.edu FU National Science Foundation; James S. McDonnell Foundation; National Institutes of Health (NIH) [MH072279, MH80758, MH079513, MH091401]; National Institute on Alcohol Abuse; Hartwell Foundation; Pritzker Neuropsychiatric Disorders Research Consortium FX We thank A. Gorun and A. Richman for assistance with data collection and analysis. A. Izquierdo and A. Holmes collected the original 5-HTT knockout mouse data. This research was supported by the National Science Foundation (C. A. H.); the James S. McDonnell Foundation, and National Institutes of Health (NIH) Grants MH072279 and MH80758 (to E. A. P.); The National Institute on Alcohol Abuse and Alcoholism Intramural Research Program (A. H.); a generous gift by the Mortimer D. Sackler, MD family (to B.J.C.); NIH Grant MH079513 (to B.J.C. and C. E. G.); and The Hartwell Foundation, the Pritzker Neuropsychiatric Disorders Research Consortium, and NIH Grant MH091401 (to C. E. G.). NR 54 TC 33 Z9 34 U1 2 U2 14 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD APR 3 PY 2012 VL 109 IS 14 BP 5493 EP 5498 DI 10.1073/pnas.1202044109 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 919BD UT WOS:000302294700076 PM 22431634 ER PT J AU Jabbi, M Kippenhan, JS Kohn, P Marenco, S Mervis, CB Morris, CA Meyer-Lindenberg, A Berman, KF AF Jabbi, Mbemba Kippenhan, J. Shane Kohn, Philip Marenco, Stefano Mervis, Carolyn B. Morris, Colleen A. Meyer-Lindenberg, Andreas Berman, Karen Faith TI The Williams syndrome chromosome 7q11.23 hemideletion confers hypersocial, anxious personality coupled with altered insula structure and function SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE brain; genetics; copy number variant; MRI; PET ID OLD-WORLD MONKEY; ANTERIOR INSULA; GENETIC CONTRIBUTIONS; SOCIAL COGNITION; WHITE-MATTER; NEURAL BASIS; GREAT APES; BRAIN; CORTEX; BEHAVIOR AB Although it is widely accepted that genes can influence complex behavioral traits such as human temperament, the underlying neurogenetic mechanisms remain unclear. Williams syndrome (WS), a rare disorder caused by a hemizygous deletion on chromosome 7q11.23, including genes important for neuronal migration and maturation (LIMK1 and CLIP2), is typified by a remarkable hypersocial but anxious personality and offers a unique opportunity to investigate this open issue. Based on the documented role of the insula in mediating emotional response tendencies and personality, we used multimodal imaging to characterize this region in WS and found convergent anomalies: an overall decrease in dorsal anterior insula (AI) gray-matter volume along with locally increased volume in the right ventral AI; compromised white-matter integrity of the uncinate fasciculus connecting the insula with the amygdala and orbitofrontal cortex; altered regional cerebral blood flow in a pattern reminiscent of the observed gray-matter alterations (i.e., widespread reductions in dorsal AI accompanied by locally increased regional cerebral blood flow in the right ventral AI); and disturbed neurofunctional interactions between the AI and limbic regions. Moreover, these genetically determined alterations of AI structure and function predicted the degree to which the atypical WS personality profile was expressed in participants with the syndrome. The AI's rich anatomical connectivity, its transmodal properties, and its involvement in the behaviors affected in WS make the observed genetically determined insular circuitry perturbations and their association with WS personality a striking demonstration of the means by which neural systems can serve as the interface between genetic variability and alterations in complex behavioral traits. C1 [Jabbi, Mbemba; Kippenhan, J. Shane; Kohn, Philip; Meyer-Lindenberg, Andreas; Berman, Karen Faith] NIMH, Sect Integrat Neuroimaging, Intramural Res Program, NIH, Bethesda, MD 20892 USA. [Jabbi, Mbemba; Kippenhan, J. Shane; Kohn, Philip; Marenco, Stefano; Meyer-Lindenberg, Andreas; Berman, Karen Faith] NIMH, Clin Brain Disorders Branch, Genes Cognit & Psychosis Program, Intramural Res Program,NIH, Bethesda, MD 20892 USA. [Mervis, Carolyn B.] Univ Louisville, Dept Psychol & Brain Sci, Neurodev Sci Lab, Louisville, KY 40208 USA. [Morris, Colleen A.] Univ Nevada, Sch Med, Dept Pediat, Las Vegas, NV 89128 USA. RP Jabbi, M (reprint author), NIMH, Sect Integrat Neuroimaging, Intramural Res Program, NIH, Bethesda, MD 20892 USA. EM jabbim@gmail.com; karen.berman@nih.gov RI Marenco, Stefano/A-2409-2008; Meyer-Lindenberg, Andreas/H-1076-2011 OI Marenco, Stefano/0000-0002-2488-2365; Meyer-Lindenberg, Andreas/0000-0001-5619-1123 FU National Institute of Mental Health, National Institutes of Health; National Institute of Neurological Disorders and Stroke [R01 NS35102] FX The authors thank Rosanna Olsen, Aaron Bonner-Jackson, and Paul Koch for their contribution toward data collection and management of the experiments and Dwight Dickinson for comments. This research was supported by the Intramural Research Program of the National Institute of Mental Health, National Institutes of Health and by National Institute of Neurological Disorders and Stroke Grant R01 NS35102 (to C.B.M.). NR 62 TC 20 Z9 20 U1 2 U2 13 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD APR 3 PY 2012 VL 109 IS 14 BP E860 EP E866 DI 10.1073/pnas.1114774109 PG 7 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 919BD UT WOS:000302294700013 PM 22411788 ER PT J AU Mulkidjanian, AY Bychkov, AY Dibrova, DV Galperin, MY Koonin, EV AF Mulkidjanian, Armen Y. Bychkov, Andrew Yu. Dibrova, Daria V. Galperin, Michael Y. Koonin, Eugene V. TI Origin of first cells at terrestrial, anoxic geothermal fields SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE prebiotic chemistry; abiotic photosynthesis; hydrothermal alteration; origin of life; Na+/K+ gradient ID TEMPLATE-DIRECTED SYNTHESIS; HYDROTHERMAL ORE-DEPOSITS; INFORMATIONAL POLYMERS; PREBIOTIC SYNTHESIS; EARLY EARTH; DIFFERENTIAL STABILITY; FORMAMIDE SOLUTIONS; MANGANESE SULFIDE; COMMON ANCESTOR; NUCLEIC-ACIDS AB All cells contain much more potassium, phosphate, and transition metals than modern (or reconstructed primeval) oceans, lakes, or rivers. Cells maintain ion gradients by using sophisticated, energy-dependent membrane enzymes (membrane pumps) that are embedded in elaborate ion-tight membranes. The first cells could possess neither ion-tight membranes nor membrane pumps, so the concentrations of small inorganic molecules and ions within protocells and in their environment would equilibrate. Hence, the ion composition of modern cells might reflect the inorganic ion composition of the habitats of protocells. We attempted to reconstruct the "hatcheries" of the first cells by combining geochemical analysis with phylogenomic scrutiny of the inorganic ion requirements of universal components of modern cells. These ubiquitous, and by inference primordial, proteins and functional systems show affinity to and functional requirement for K+, Zn2+, Mn2+, and phosphate. Thus, protocells must have evolved in habitats with a high K+/Na+ ratio and relatively high concentrations of Zn, Mn, and phosphorous compounds. Geochemical reconstruction shows that the ionic composition conducive to the origin of cells could not have existed in marine settings but is compatible with emissions of vapor-dominated zones of inland geothermal systems. Under the anoxic, CO2-dominated primordial atmosphere, the chemistry of basins at geothermal fields would resemble the internal milieu of modern cells. The precellular stages of evolution might have transpired in shallow ponds of condensed and cooled geothermal vapor that were lined with porous silicate minerals mixed with metal sulfides and enriched in K+, Zn2+, and phosphorous compounds. C1 [Mulkidjanian, Armen Y.; Dibrova, Daria V.] Univ Osnabruck, Sch Phys, D-49069 Osnabruck, Germany. [Mulkidjanian, Armen Y.] Moscow MV Lomonosov State Univ, AN Belozersky Inst Physicochem Biol, Moscow 119992, Russia. [Bychkov, Andrew Yu.] Moscow MV Lomonosov State Univ, Sch Geol, Moscow 119992, Russia. [Dibrova, Daria V.] Moscow MV Lomonosov State Univ, Sch Bioengn & Bioinformat, Moscow 119992, Russia. [Galperin, Michael Y.; Koonin, Eugene V.] NIH, Natl Ctr Biotechnol Informat, Natl Lib Med, Bethesda, MD 20894 USA. RP Mulkidjanian, AY (reprint author), Univ Osnabruck, Sch Phys, D-49069 Osnabruck, Germany. EM amulkid@uos.de; koonin@ncbi.nlm.nih.gov RI Galperin, Michael/B-5859-2013; Mulkidjanian, Armen/J-8086-2013; Bychkov, Andrey/R-6693-2016 OI Galperin, Michael/0000-0002-2265-5572; Mulkidjanian, Armen/0000-0001-5844-3064; Bychkov, Andrey/0000-0003-2560-6423 FU Deutsche Forschungsgemeinschaft (DFG) [DFG-Mu-1285/1-10, DFG-436-RUS 113/963/0-1]; Russian Government [02.740.11.5228]; Volkswagen Foundation; EU COST [CM0902]; Deutscher Akademischer Austausch Dienst; Russian Foundation for Basic Research [10-05-00320, 0-04-91331]; National Library of Medicine at the National Institutes of Health FX Valuable discussions with Drs. D. A. Cherepanov, M. Eigen, R. M. Hazen, G. F. Joyce, M. J. van Kranendonk, V. N. Kompaninchenko, D.-H. Lankenau, D. L. Pinti, M. J. Russell, V. P. Skulachev, H.-J. Steinhoff, J. Szostak, N. E. Voskoboynikova, R. J. P. Williams, Y. I. Wolf and A. Yonath are greatly appreciated. The authors are thankful to Drs. A. S. Karyagina and I. Y. Nikolaeva for providing photographs of boiling mud pots. This study was supported by Deutsche Forschungsgemeinschaft (DFG) Grants DFG-Mu-1285/1-10 and DFG-436-RUS 113/963/0-1 (to A. Y. M.), Russian Government Grant 02.740.11.5228 (to A. Y. M.), the Volkswagen Foundation (A. Y. M.), EU COST CM0902 Action (A. Y. M.), Deutscher Akademischer Austausch Dienst (D.V.D.), Russian Foundation for Basic Research Grants 10-05-00320 (to A. Y. B.) and 0-04-91331 (to D. V. D.), and the Intramural Research Program of the National Library of Medicine at the National Institutes of Health (M. Y. G. and E.V.K). NR 145 TC 72 Z9 83 U1 16 U2 91 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD APR 3 PY 2012 VL 109 IS 14 BP E821 EP E830 DI 10.1073/pnas.1117774109 PG 10 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 919BD UT WOS:000302294700009 PM 22331915 ER PT J AU Pallan, PS Marquez, VE Egli, M AF Pallan, Pradeep S. Marquez, Victor E. Egli, Martin TI The Conformationally Constrained N-Methanocarba-dT Analogue Adopts an Unexpected C4 '-exo Sugar Pucker in the Structure of a DNA Hairpin SO BIOCHEMISTRY LA English DT Article ID NUCLEOSIDE ANALOGS; CRYSTAL-STRUCTURE; NUCLEIC-ACIDS; RNA; NUCLEOTIDES; OLIGONUCLEOTIDES; THERAPEUTICS; NORTH; RING AB Incorporation of a bicyclo[3.1.0]hexane scaffold into the nucleoside sugar was devised to lock the embedded cyclopentane ring in conformations that mimic the furanose North and South sugar puckers. To analyze the effects of North-methanocarba-2'-deoxythymidine (N-MCdT) on the B-form DNA, we crystallized d(CGCGAA[mcTmcT]CGCG) with two N-MCdTs. Instead of a duplex, the 12mer forms a tetraloop hairpin, whereby loop N-MCdTs adopt the C4'-exo pucker (NE; P = 50 degrees). Thus, the bicyclic framework does not limit the pucker to the anticipated C2'-exo range (NNW; P = 18 degrees). C1 [Pallan, Pradeep S.; Egli, Martin] Vanderbilt Univ, Dept Biochem, Sch Med, Nashville, TN 37232 USA. [Marquez, Victor E.] NCI, Biol Chem Lab, Ctr Canc Res, Frederick, MD 21702 USA. RP Egli, M (reprint author), Vanderbilt Univ, Dept Biochem, Sch Med, Nashville, TN 37232 USA. EM martin.egli@vanderbilt.edu FU NIH [GM55237]; U.S. DOE, Office of Science, Office of Basic Energy Sciences [DE-AC02-06CH11357] FX Supported by NIH Grant GM55237 (to M.E.). Use of the APS was supported by the U.S. DOE, Office of Science, Office of Basic Energy Sciences, Contract DE-AC02-06CH11357. NR 35 TC 9 Z9 9 U1 0 U2 4 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0006-2960 J9 BIOCHEMISTRY-US JI Biochemistry PD APR 3 PY 2012 VL 51 IS 13 BP 2639 EP 2641 DI 10.1021/bi300215k PG 3 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 926KW UT WOS:000302830900001 PM 22409313 ER PT J AU Agniswamy, J Shen, CH Aniana, A Sayer, JM Louis, JM Weber, IT AF Agniswamy, Johnson Shen, Chen-Hsiang Aniana, Annie Sayer, Jane M. Louis, John M. Weber, Irene T. TI HIV-1 Protease with 20 Mutations Exhibits Extreme Resistance to Clinical Inhibitors through Coordinated Structural Rearrangements SO BIOCHEMISTRY LA English DT Article ID VIRUS TYPE-1 PROTEASE; RESOLUTION CRYSTAL-STRUCTURES; DRUG-RESISTANCE; ACTIVE-SITE; MOLECULAR CHARACTERIZATION; MULTIDRUG-RESISTANCE; MUTANTS; BINDING; AMPRENAVIR; DARUNAVIR AB The escape mutant of HIV-1 protease (PR) containing 20 mutations (PR20) undergoes efficient polyprotein processing even in the presence of clinical protease inhibitors (PIs). PR20 shows >3 orders of magnitude decreased affinity for Pis darunavir (DRV) and saquinavir (SQV) relative to PR Crystal structures of PR20 crystallized with yttrium, substrate analogue p2-NC, DRV, and SQV reveal three distinct conformations of the flexible flaps and diminished interactions with inhibitors through the combination of multiple mutations. PR20 with yttrium at the active site exhibits widely separated flaps lacking the usual intersubunit contacts seen in other inhibitor-free dimers. Mutations of residues 35-37 in the hinge loop eliminate interactions and perturb the flap conformation. Crystals of P PR20/p2-NC contain one uninhibited dimer with one very open flap and one closed flap and a second inhibitor-bound dimer in the closed form showing six fewer hydrogen bonds with the substrate analogue relative to wild-type PR PR20 complexes with PIs exhibit expanded S2/S2' pockets and fewer PI interactions arising from coordinated effects of mutations throughout the structure, in agreement with the strikingly reduced affinity. In particular, insertion of the large aromatic side chains of L10F and L33F alters intersubunit interactions and widens the PI binding site through a network of hydrophobic contacts. The two very open conformations of PR20 as well as the expanded binding site of the inhibitor-bound closed form suggest possible approaches for modifying inhibitors to target extreme drug-resistant HIV. C1 [Agniswamy, Johnson; Shen, Chen-Hsiang; Weber, Irene T.] Georgia State Univ, Dept Biol, Mol Basis Dis Program, Atlanta, GA 30303 USA. [Aniana, Annie; Sayer, Jane M.; Louis, John M.] NIDDK, Chem Phys Lab, NIH, DHHS, Bethesda, MD 20892 USA. RP Weber, IT (reprint author), Georgia State Univ, Dept Biol, Mol Basis Dis Program, POB 4010, Atlanta, GA 30303 USA. EM iweber@gsu.edu RI shen, chen-hsiang/D-7309-2016 FU NIDDK; National Institutes of Health (NIH) [GM062920]; Office of the Director, NIH; U.S. Department of Energy, Office of Science, Office of Basic Energy Sciences [W-31-109-Eng-38]; Georgia State University FX This research was supported, in whole or in part, by the Intramural Research Program of the NIDDK, National Institutes of Health (NIH), Intramural AIDS-Targeted Antiviral Program of the Office of the Director, NIH, and Grant GM062920 from the NIH. 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 W-31-109-Eng-38.; Chen-Hsiang Shen was supported in part by the Georgia State University Molecular Basis of Disease Fellowship and the Georgia State University Research Program Enhancement Award in Bioinformatics. This research was authored, in whole or in part, by National Institutes of Health staff. Data were collected at the Southeast Regional Collaborative Access Team (SER-CAT) beamline 22ID at the Advanced Photon Source, Argonne National Laboratory. Supporting institutions may be found at www.ser-cat.org/members.html. DRV and SQV were obtained through the NIH AIDS Research and Reference Reagent Program, Division of AIDS, NIAID, NIH. NR 51 TC 40 Z9 40 U1 0 U2 14 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0006-2960 J9 BIOCHEMISTRY-US JI Biochemistry PD APR 3 PY 2012 VL 51 IS 13 BP 2819 EP 2828 DI 10.1021/bi2018317 PG 10 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 926KW UT WOS:000302830900019 PM 22404139 ER PT J AU Mandal, D Moitra, K Ghosh, D Xia, D Dey, S AF Mandal, Debjani Moitra, Karobi Ghosh, Debabrata Xia, Di Dey, Saibal TI Evidence for Modulatory Sites at the Lipid-Protein Interface of the Human Multidrug Transporter P-Glycoprotein SO BIOCHEMISTRY LA English DT Article ID NICOTINIC ACETYLCHOLINE-RECEPTOR; DRUG-BINDING; MEMBRANE-PROTEINS; ALLOSTERIC MODULATION; PLASMA-MEMBRANE; LIPID/PROTEIN INTERFACE; CYTOPLASMIC LEAFLET; TRANSITION-STATE; KINETIC-ANALYSIS; ATPASE ACTIVITY AB The human multidrug transporter P-glycoprotein (Pgp or ABCB1) sets up pharmacological barriers to many clinically important drugs, a therapeutic remedy for which has yet to be formulated. For the rational design of mechanism-based inhibitors (or modulators), it is necessary to map the potential sites for modulator interaction and understand their modes of communication with the other functional domains of Pgp. In this study, combining directed mutagenesis with homology modeling, we provide evidence of two modulator-specific sites at the lipid protein interface of Pgp. Targeting 21 variant positions in the COOH-terminal transmembrane (TM) regions, we find residues M948 (in TM11) and F983, M986, V988, and Q990 (all four in TM12) critically involved in substrate-site modulation by a thioxanthene-based allosteric modulator cis-(Z)-flupentixol. Interestingly, for ATP-site modulation by the same modulator, only two (M948 and Q990) of those four residues appear indispensable, together with two additional residues, T837 and I864 in TM9 and TM10, respectively, suggesting independent modes of communication linking the allosteric site with the substrate binding and ATPase domains. None of the seven residues identified prove to be critical for modulation of the substrate or ATP sites by Pgp modulators that are transported by the pump, such as cyclosporin A or verapamil, indicating their specificity for cis-(Z)-flupentixol. On the other hand, ATP-site modulation by verapamil proves to be highly sensitive to replacement at positions F716 (in TM7) and 1765 (in TM8), and to a more moderate extent at 1764 and L772 (both in TM8). Homology modeling based on the known crystal structures of the bacterial multidrug transporter SAV1866 and the mouse Pgp homologue maps the identified residues primarily at the lipid-protein interface of Pgp, in two spatially distinct modulator-specific clusters. The two modulatory sites demonstrate negative synergism in influencing ATP hydrolysis, consolidating their spatial distinctness. Because Pgp is known to recruit drug molecules directly from the lipid bilayer, identification of modulatory sites at the lipid-protein interface and at the same time outside the conventional central drug binding cavity is mechanistically revealing. C1 [Mandal, Debjani; Moitra, Karobi; Ghosh, Debabrata; Dey, Saibal] Uniformed Serv Univ Hlth Sci, Sch Med, Dept Biochem, Bethesda, MD 20814 USA. [Xia, Di] NCI, Cell Biol Lab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. RP Dey, S (reprint author), Uniformed Serv Univ Hlth Sci, Sch Med, Dept Biochem & Mol Biol, 4301 Jones Bridge Rd, Bethesda, MD 20814 USA. EM sdey@usuhs.mil OI Ghosh, Debabrata/0000-0002-6571-304X FU U.S. Public Health Services [GM067926]; Uniformed Services University FX The work was supported by U.S. Public Health Services Grant GM067926 and Uniformed Services University Grant C071FU. NR 72 TC 9 Z9 10 U1 0 U2 10 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0006-2960 J9 BIOCHEMISTRY-US JI Biochemistry PD APR 3 PY 2012 VL 51 IS 13 BP 2852 EP 2866 DI 10.1021/bi201479k PG 15 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 926KW UT WOS:000302830900022 PM 22360349 ER PT J AU Reuven, EM Dadon, Y Viard, M Manukovsky, N Blumenthal, R Shai, Y AF Reuven, Eliran Moshe Dadon, Yakir Viard, Mathias Manukovsky, Nurit Blumenthal, Robert Shai, Yechiel TI HIV-1 gp41 Transmembrane Domain Interacts with the Fusion Peptide: Implication in Lipid Mixing and Inhibition of Virus-Cell Fusion SO BIOCHEMISTRY LA English DT Article ID MEMBRANE-SPANNING DOMAIN; GLYCOPROTEIN-MEDIATED FUSION; COLI ASPARTATE RECEPTOR; ENVELOPE GLYCOPROTEIN; PHOSPHOLIPID-MEMBRANES; CONFORMATIONAL-CHANGES; IN-VIVO; INFLUENZA HEMAGGLUTININ; COMMON PRINCIPLES; PORE FORMATION AB Fusion of the human immunodeficiency virus (HIV) with target cells is mediated by the gp41 subunit of the envelope protein. Mutation and deletion studies within the transmembrane domain (TMD) of intact gp41 influenced its fusion activity. In addition, current models suggest that the TMD is in proximity with the fusion peptide (FP) at the late fusion stages, but there are no direct experimental data to support this hypothesis. Here, we investigated the TMD focusing on two regions: the N-terminal containing the GxxxG motif and the C-terminal containing the GLRI motif; which is conserved among the TMDs of HIV and the T-cell receptor. Studies utilizing the ToxR expression system combined with synthetic peptides and their fluorescent analogues derived from TMD revealed that the GxxxG motif is important for TMD self-association, whereas the C-terminal region is for its heteroassociation with FP. Functionally, all three TMD peptides induced lipid mixing that was enhanced significantly upon mixing with FP. Furthermore, the TMD peptides inhibited virus-cell fusion apparently through their interaction with their endogenous counterparts. Notably, the R2E mutant (in the GLRI) was significantly less potent than the two others. Overall, our findings provide experimental evidence that HIV-1 TMD contributes to membrane assembly and function of the HIV-1 envelope. Owing to similarities between functional domains within viruses, these findings suggest that the TMDs and FPs may contribute similarly in other viruses as well. C1 [Reuven, Eliran Moshe; Dadon, Yakir; Manukovsky, Nurit; Shai, Yechiel] Weizmann Inst Sci, Dept Biol Chem, IL-76100 Rehovot, Israel. [Viard, Mathias; Blumenthal, Robert] SAIC Frederick Inc, Basic Res Program, Frederick Natl Lab Canc Res, Frederick, MD 21702 USA. [Viard, Mathias] NCI, Nanobiol Program, Ctr Canc Res, Frederick, MD 21701 USA. RP Shai, Y (reprint author), Weizmann Inst Sci, Dept Biol Chem, IL-76100 Rehovot, Israel. EM Yechiel.Shai@weizmann.ac.il FU Israel Science Foundation; Frederick National Laboratory for Cancer Research, National Institutes of Health [HHSN261200800001E]; NIH, Frederick National Lab, Center for Cancer Research FX This study was supported by the Israel Science Foundation (to Y.S.) and in part with Federal funds from the Frederick National Laboratory for Cancer Research, National Institutes of Health, under contract HHSN261200800001E (to R.B.). The content of this publication does not necessarily reflect the views or policies of the Department of Health and Human Services, nor does mention of trade names, commercial products or organizations imply endorsement by the US Government. This research was supported in part by the Intramural Research Program of NIH, Frederick National Lab, Center for Cancer Research (to R.B.). Y.S. is the Harold S. and Harriet B. Brady Professorial Chair in Cancer Research. NR 90 TC 30 Z9 30 U1 2 U2 14 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0006-2960 J9 BIOCHEMISTRY-US JI Biochemistry PD APR 3 PY 2012 VL 51 IS 13 BP 2867 EP 2878 DI 10.1021/bi201721r PG 12 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 926KW UT WOS:000302830900023 PM 22413880 ER PT J AU Shah, MR Starling, RC Longacre, LS Mehra, MR AF Shah, Monica R. Starling, Randall C. Longacre, Lisa Schwartz Mehra, Mandeep R. CA Working Grp Participants TI Heart Transplantation Research in the Next Decade-A Goal to Achieving Evidence-Based Outcomes SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Review DE heart transplantation; NHLBI; research; working group ID CARDIAC ALLOGRAFT VASCULOPATHY; ANTIBODY-MEDIATED REJECTION; CONVERTING ENZYME-INHIBITORS; VENTRICULAR ASSIST DEVICES; PULMONARY-HYPERTENSION; INTRAVASCULAR ULTRASOUND; INTERNATIONAL SOCIETY; LUNG TRANSPLANTATION; DONOR; RECIPIENTS AB The National Heart, Lung, and Blood Institute (NHLBI) convened a Working Group (WG) on August 5 to 6, 2010 in Bethesda, Maryland to discuss future directions of research in heart transplantation (HT). The WG was composed of researchers with expertise in the basic science, clinical science, and epidemiological aspects of advanced heart failure and HT. These experts were asked to identify the highest priority research gaps in the field and make recommendations for future research strategies. The WG was also asked to include approaches that capitalize on current scientific opportunities and focus on areas that required unique NHLBI leadership. Finally, the WG was charged with developing recommendations that would have short-and long-term impact on the field of HT. The WG participants reviewed key areas in HT and identified the most urgent knowledge gaps. These gaps were then organized into the following 4 specific research directions: 1) enhanced phenotypic characterization of the pre-transplant population; 2) donor-recipient optimization strategies; 3) individualized immunosuppression therapy; and, 4) investigations of immune and non-immune factors affecting late cardiac allograft outcomes. Finally, because the HT population is relatively small compared with other patient groups, the WG strongly urged concerted efforts to enroll every transplant recipient into a clinical study and to increase collaborative networks to optimize research in this field. (J Am Coll Cardiol 2012; 59: 1263-9) (C) 2012 by the American College of Cardiology Foundation C1 [Shah, Monica R.] NHLBI, Heart Failure & Arrhythmias Branch, Div Cardiovasc Sci, Rockledge Ctr 2, Bethesda, MD 20892 USA. [Starling, Randall C.] Case Western Reserve Univ, Sch Med, Cleveland Clin, Lerner Coll Med, Cleveland, OH USA. [Starling, Randall C.] Cleveland Clin Fdn, Cleveland, OH 44195 USA. [Mehra, Mandeep R.] Harvard Univ, Sch Med, Boston, MA USA. [Mehra, Mandeep R.] Brigham & Womens Hosp, Boston, MA 02115 USA. RP Shah, MR (reprint author), NHLBI, Heart Failure & Arrhythmias Branch, Div Cardiovasc Sci, Rockledge Ctr 2, 6701 Rockledge Dr,MSC 7956, Bethesda, MD 20892 USA. EM shahmr@nhlbi.nih.gov RI Fung, John/A-2679-2012 FU Division of Cardiovascular Sciences, NHLBI, NIH; NIAID/NIH; Johnson and Johnson Corp.; NHLBI/NIH FX Support for the working group was provided by the Division of Cardiovascular Sciences, NHLBI, NIH. Drs. Starling and Mehra served as Chairs of the Workshop. Drs. Shah and Schwartz Longacre are employees of NIH. Dr. Starling has received grant support from NIAID/NIH and Johnson and Johnson Corp., has served as a consultant to Medtronic, WellPoint, Novartis, Anthem Ins., and Bio Control Medical Ltd., and owns stock in Cardiomems that is worth <$1,000. Dr. Mehra has received grant support from NHLBI/NIH and served as a consultant to Medtronic, St. Judes, Geron, J and J, and GlaxoSmithKline. A full list of the Working Group Participants is listed in the Appendix at the end of the paper. NR 34 TC 17 Z9 17 U1 1 U2 4 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 APR 3 PY 2012 VL 59 IS 14 BP 1263 EP 1269 DI 10.1016/j.jacc.2011.11.050 PG 7 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 916ZD UT WOS:000302140800002 PM 22464255 ER PT J AU Amyot, F Zimmermann, T Riley, J Kainerstorfer, JM Chernomordik, V Mooshagian, E Najafizadeh, L Krueger, F Gandjbakhche, AH Wassermann, EM AF Amyot, Franck Zimmermann, Trelawny Riley, Jason Kainerstorfer, Jana M. Chernomordik, Victor Mooshagian, Eric Najafizadeh, Laleh Krueger, Frank Gandjbakhche, Amir H. Wassermann, Eric M. TI Normative database of judgment of complexity task with functional near infrared spectroscopy-Application for TBI SO NEUROIMAGE LA English DT Article DE Near infrared spectroscopy; Frameless stereotaxy; Frontal cortex; Group study ID TRAUMATIC BRAIN-INJURY; VIETNAM HEAD-INJURY; ACTIVATION; TECHNOLOGY; LOCATIONS AB The ability to assess frontal lobe function in a rapid, objective, and standardized way, without the need for expertise in cognitive test administration might be particularly helpful in mild traumatic brain injury (TBI), where objective measures are needed. Functional near infrared spectroscopy (fNIRS) is a reliable technique to noninvasively measure local hemodynamic changes in brain areas near the head surface. In this paper, we are combining fNIRS and frameless stereotaxy which allowed us to co-register the functional images with previously acquired anatomical MRI volumes. In our experiment, the subjects were asked to perform a task, evaluating the complexity of daily life activities, previously shown with fMRI to activate areas of the anterior frontal cortex. We reconstructed averaged oxyhemoglobin and deoxyhemoglobin data from 20 healthy subjects in a spherical coordinate. The spherical coordinate is a natural representation of surface brain activation projection. Our results show surface activation projected from the medial frontopolar cortex which is consistent with previous fMRI results. With this original technique, we will construct a normative database for a simple cognitive test which can be useful in evaluating cognitive disability such as mild traumatic brain injury. Published by Elsevier Inc. C1 [Amyot, Franck; Riley, Jason; Kainerstorfer, Jana M.; Chernomordik, Victor; Najafizadeh, Laleh; Gandjbakhche, Amir H.] Eunice Kennedy Shriver NICHD, NIH, Program Pediat Imaging & Tissue Sci, Sect Analyt & Funct Biophoton, Bethesda, MD 20892 USA. [Amyot, Franck; Mooshagian, Eric; Najafizadeh, Laleh] Henry M Jackson Fdn, Rockville, MD 20852 USA. [Amyot, Franck; Zimmermann, Trelawny; Mooshagian, Eric; Wassermann, Eric M.] Natl Inst Neurol Disorders & Stroke, Behav Neurol Unit, NIH, Bethesda, MD USA. [Krueger, Frank] George Mason Univ, Krasnow Inst Adv Study, Fairfax, VA 22030 USA. RP Gandjbakhche, AH (reprint author), Eunice Kennedy Shriver NICHD, NIH, Program Pediat Imaging & Tissue Sci, Sect Analyt & Funct Biophoton, Bethesda, MD 20892 USA. EM amir@helix.nih.gov FU Eunice Kennedy Shriver National Institute of Child Health and Human Development; National Institute of Neurological Disorders and Stroke; Center for Neuroscience and Regenerative Medicine FX We thank Dr. Jordan Grafman for his valuable suggestions and comments on this project. We also acknowledge the funding of the intramural program of the Eunice Kennedy Shriver National Institute of Child Health and Human Development, the National Institute of Neurological Disorders and Stroke and Center for Neuroscience and Regenerative Medicine. NR 29 TC 9 Z9 9 U1 2 U2 8 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1053-8119 J9 NEUROIMAGE JI Neuroimage PD APR 2 PY 2012 VL 60 IS 2 BP 879 EP 883 DI 10.1016/j.neuroimage.2012.01.104 PG 5 WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA 932ED UT WOS:000303272300005 PM 22306800 ER PT J AU Caria, A de Falco, S Venuti, P Lee, S Esposito, G Rigo, P Birbaumer, N Bornstein, MH AF Caria, Andrea de Falco, Simona Venuti, Paola Lee, Sangkyun Esposito, Gianluca Rigo, Paola Birbaumer, Niels Bornstein, Marc H. TI Species-specific response to human infant faces in the premotor cortex SO NEUROIMAGE LA English DT Article DE Infant faces; fMRI; Species-specific; Premotor cortex; Supplementary motor area ID MATERNAL RESPONSIVENESS; FMRI DATA; BRAIN; SUPPLEMENTARY; PREPAREDNESS; POTENTIALS; ATTACHMENT; BEHAVIORS; MOVEMENTS; INFERENCE AB The human infant face represents an essential source of communicative signals on the basis of which adults modulate their interactions with infants. Behavioral studies demonstrate that infants' faces activate sensitive and attuned responses in adults through their gaze, face expression, voice, and gesture. In this study we aimed to identify brain responses that underlie adults' general propensity to respond to infant faces. We recorded fMRI during adults' (non-parents) processing of unfamiliar infant faces compared to carefully matched adult faces and infrahuman mammal infant and adult faces. Human infant faces activated several brain systems including the lateral premotor cortex, supplementary motor area, cingulate cortex, anterior insula and the thalamus. Activation of these brain circuits suggests adults' preparation for communicative behavior with infants as well as attachment and caregiving. The same brain regions preferentially responded to human infant faces when compared to animal infant faces, indicating species-specific adult brain responses. Moreover, results of support vector machine based classification analysis indicated that these regions allowed above chance-level prediction of brain state during perception of human infant faces. The complex of brain responses to human infant faces appears to include biological mechanisms that underlie responsiveness and a caring inclination toward young children which appear to transcend adult's biological relationship to the baby. (c) 2011 Elsevier Inc. All rights reserved. C1 [Caria, Andrea; Birbaumer, Niels] Univ Tubingen, Inst Med Psychol & Behav Neurobiol, D-72070 Tubingen, Germany. [Caria, Andrea; de Falco, Simona; Venuti, Paola; Esposito, Gianluca; Rigo, Paola] Univ Trent, Dipartimento Sci Cogniz & Formaz, Trento, Italy. [Lee, Sangkyun] Max Planck Inst Biol Cybernet, Tubingen, Germany. [Esposito, Gianluca] RIKEN Brain Sci Inst, Saitama, Japan. [Bornstein, Marc H.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, NIH, Bethesda, MD USA. RP Caria, A (reprint author), Univ Tubingen, Inst Med Psychol & Behav Neurobiol, Gartenstr 29, D-72070 Tubingen, Germany. EM andrea.caria@uni-tuebingen.de RI Esposito, Gianluca/B-1374-2012 OI Esposito, Gianluca/0000-0002-9442-0254 FU Intramural NIH HHS [ZIA HD001119-25] NR 70 TC 28 Z9 28 U1 1 U2 11 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1053-8119 J9 NEUROIMAGE JI Neuroimage PD APR 2 PY 2012 VL 60 IS 2 BP 884 EP 893 DI 10.1016/j.neuroimage.2011.12.068 PG 10 WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA 932ED UT WOS:000303272300006 PM 22230948 ER PT J AU Ozarslan, E Shepherd, TM Koay, CG Blackband, SJ Basser, PJ AF Oezarslan, Evren Shepherd, Timothy M. Koay, Cheng Guan Blackband, Stephen J. Basser, Peter J. TI Temporal scaling characteristics of diffusion as a new MRI contrast: Findings in rat hippocampus SO NEUROIMAGE LA English DT Article DE Diffusion time; q-Space; Scaling; Power law; Fractal; Anomalous diffusion; Anisotropy; Rician; Noise floor; SHORE; DWI ID FRACTIONAL ORDER CALCULUS; TIME-DEPENDENT DIFFUSION; ANOMALOUS DIFFUSION; HUMAN BRAIN; BIOLOGICAL TISSUES; TENSOR; NMR; WATER; SIGNAL; MODEL AB Features of the diffusion-time dependence of the diffusion-weighted magnetic resonance imaging (MRI) signal provide a new contrast that could be altered by numerous biological processes and pathologies in tissue at microscopic length scales. An anomalous diffusion model, based on the theory of Brownian motion in fractal and disordered media, is used to characterize the temporal scaling (TS) characteristics of diffusion-related quantities, such as moments of the displacement and zero-displacement probabilities, in excised rat hippocampus specimens. To reduce the effect of noise in magnitude-valued MRI data, a novel numerical procedure was employed to yield accurate estimation of these quantities even when the signal falls below the noise floor. The power-law dependencies characterize the TS behavior in all regions of the rat hippocampus, providing unique information about its microscopic architecture. The relationship between the TS characteristics and diffusion anisotropy is investigated by examining the anisotropy of TS, and conversely, the TS of anisotropy. The findings suggest the robustness of the technique as well as the reproducibility of estimates. TS characteristics of the diffusion-weighted signals could be used as a new and useful marker of tissue microstructure. (c) 2012 Elsevier Inc. All rights reserved. C1 [Oezarslan, Evren; Basser, Peter J.] NICHD, Sect Tissue Biophys & Biomimet, PPITS, NIH, Bethesda, MD 20892 USA. [Oezarslan, Evren] Uniformed Serv Univ Hlth Sci, Ctr Neurosci & Regenerat Med, Bethesda, MD 20814 USA. [Shepherd, Timothy M.] Univ Calif San Francisco, Dept Radiol & Biomed Imaging, San Francisco, CA 94143 USA. [Koay, Cheng Guan] Univ Wisconsin, Dept Med Phys, Madison, WI 53705 USA. [Blackband, Stephen J.] Univ Florida, Dept Neurosci, Gainesville, FL 32610 USA. [Blackband, Stephen J.] Natl High Magnet Field Lab, Tallahassee, FL 32310 USA. RP Ozarslan, E (reprint author), NICHD, Sect Tissue Biophys & Biomimet, PPITS, NIH, Bethesda, MD 20892 USA. EM evren@helix.nih.gov RI Ozarslan, Evren/B-4858-2013; Basser, Peter/H-5477-2011 OI Ozarslan, Evren/0000-0003-0859-1311; FU Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD), National Institutes of Health (NIH); NIH [1R01EB012874]; Department of Defense in the Center for Neuroscience and Regenerative Medicine (CNRM); Henry M. Jackson Foundation (HJF); National Science Foundation (NSF) via the National High Magnetic Field Laboratory (NHMFL) FX Support for this work included funding from: (i) the Intramural Research Program of the Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD), National Institutes of Health (NIH). (ii) NIH grant number 1R01EB012874. (iii) Department of Defense in the Center for Neuroscience and Regenerative Medicine (CNRM) and the Henry M. Jackson Foundation (HJF). (iv) National Science Foundation (NSF) via the National High Magnetic Field Laboratory (NHMFL). We thank Liz Salak for editing the manuscript and Alexandru V. Avram for helpful discussions. NR 76 TC 14 Z9 14 U1 0 U2 14 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1053-8119 EI 1095-9572 J9 NEUROIMAGE JI Neuroimage PD APR 2 PY 2012 VL 60 IS 2 BP 1380 EP 1393 DI 10.1016/j.neuroimage.2012.01.105 PG 14 WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA 932ED UT WOS:000303272300051 PM 22306798 ER PT J AU Burkart, AD Xiong, B Baibakov, B Jimenez-Movilla, M Dean, J AF Burkart, Anna D. Xiong, Bo Baibakov, Boris Jimenez-Movilla, Maria Dean, Jurrien TI Ovastacin, a cortical granule protease, cleaves ZP2 in the zona pellucida to prevent polyspermy SO JOURNAL OF CELL BIOLOGY LA English DT Article ID GOLDEN-HAMSTER EGGS; MOUSE EGGS; SPERM BINDING; SULFATED GLYCOPROTEIN; ASTACIN FAMILY; BLOCK; MICE; METALLOENDOPEPTIDASES; FERTILIZATION; ANTIBODIES AB The mouse zona pellucida is composed of three glycoproteins (ZP1, ZP2, and ZP3), of which ZP2 is proteolytically cleaved after gamete fusion to prevent polyspermy. This cleavage is associated with exocytosis of cortical granules that are peripherally located subcellular organelles unique to ovulated eggs. Based on the cleavage site of ZP2, ovastacin was selected as a candidate protease. Encoded by the single-copy Astl gene, ovastacin is an oocyte-specific member of the astacin family of metalloendoproteases. Using specific antiserum, ovastacin was detected in cortical granules before, but not after, fertilization. Recombinant ovastacin cleaved ZP2 in native zonae pellucidae, documenting that ZP2 was a direct substrate of this metalloendoprotease. Female mice lacking ovastacin did not cleave ZP2 after fertilization, and mouse sperm bound as well to Astl-null two-cell embryos as they did to normal eggs. Ovastacin is a pioneer component of mouse cortical granules and plays a definitive role in the postfertilization block to sperm binding that ensures monospermic fertilization and successful development. C1 [Burkart, Anna D.; Xiong, Bo; Baibakov, Boris; Jimenez-Movilla, Maria; Dean, Jurrien] NIDDK, Lab Cellular & Dev Biol, NIH, Bethesda, MD 20892 USA. RP Dean, J (reprint author), NIDDK, Lab Cellular & Dev Biol, NIH, Bethesda, MD 20892 USA. EM jurrien@helix.nih.gov RI Jimenez-Movilla, Maria/I-1004-2015 OI Jimenez-Movilla, Maria/0000-0002-1572-8219 FU National Institute of Diabetes and Digestive and Kidney Diseases of the National Institutes of Health FX This research was support by the Intramural Research Program of the National Institute of Diabetes and Digestive and Kidney Diseases of the National Institutes of Health. NR 42 TC 57 Z9 61 U1 1 U2 24 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 APR 2 PY 2012 VL 197 IS 1 BP 37 EP 44 DI 10.1083/jcb.201112094 PG 8 WC Cell Biology SC Cell Biology GA 921KN UT WOS:000302476600007 PM 22472438 ER PT J AU David, A Dolan, BP Hickman, HD Knowlton, JJ Clavarino, G Pierre, P Bennink, JR Yewdell, JW AF David, Alexandre Dolan, Brian P. Hickman, Heather D. Knowlton, Jonathan J. Clavarino, Giovanna Pierre, Philippe Bennink, Jack R. Yewdell, Jonathan W. TI Nuclear translation visualized by ribosome-bound nascent chain puromycylation SO JOURNAL OF CELL BIOLOGY LA English DT Article ID NONSENSE-MEDIATED DECAY; MESSENGER-RNA TRANSLATION; PROTEIN-SYNTHESIS; MAMMALIAN-CELLS; ESCHERICHIA-COLI; INITIATION; COMPLEXES; INHIBITORS; EXPRESSION; NUCLEOLUS AB Whether protein translation occurs in the nucleus is contentious. To address this question, we developed the ribopuromycylation method (RPM), which visualizes translation in cells via standard immunofluorescence microscopy. The RPM is based on ribosome-catalyzed puromycylation of nascent chains immobilized on ribosomes by antibiotic chain elongation inhibitors followed by detection of puromycylated ribosome-bound nascent chains with a puromycin (PMY)-specific monoclonal antibody in fixed and permeabilized cells. The RPM correlates localized translation with myriad processes in cells and can be applied to any cell whose translation is sensitive to PMY. In this paper, we use the RPM to provide evidence for translation in the nucleoplasm and nucleolus, which is regulated by infectious and chemical stress. C1 [David, Alexandre; Dolan, Brian P.; Hickman, Heather D.; Knowlton, Jonathan J.; Bennink, Jack R.; Yewdell, Jonathan W.] NIAID, Viral Dis Lab, NIH, Bethesda, MD 20892 USA. [Clavarino, Giovanna; Pierre, Philippe] Ctr Immunol Marseille Luminy Aix Marseille Univ, F-13288 Marseille, France. [Clavarino, Giovanna; Pierre, Philippe] INSERM, U1104, F-13288 Marseille, France. [Clavarino, Giovanna; Pierre, Philippe] CNRS, Unite Mixte Rech 7280, F-13288 Marseille, France. RP Yewdell, JW (reprint author), NIAID, Viral Dis Lab, NIH, Bethesda, MD 20892 USA. EM jyewdell@nih.gov RI David, Alexandre/B-2447-2013; Clavarino, Giovanna/M-7174-2014; OI David, Alexandre/0000-0003-3365-1339; pierre, philippe/0000-0003-0863-8255 FU Division of Intramural Research; National Institute of Allergy and Infectious Diseases; Ligue National Contre le Cancer; Human Frontier Science Program; European Network of Excellence DC-THERA FX This work was generously supported by the Division of Intramural Research and the National Institute of Allergy and Infectious Diseases and by grants to P. Pierre from Ligue National Contre le Cancer, the Human Frontier Science Program, and the European Network of Excellence DC-THERA. NR 50 TC 90 Z9 91 U1 1 U2 27 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 APR 2 PY 2012 VL 197 IS 1 BP 45 EP 57 DI 10.1083/jcb.201112145 PG 13 WC Cell Biology SC Cell Biology GA 921KN UT WOS:000302476600008 PM 22472439 ER PT J AU Djousse, L Biggs, ML Ix, JH Kizer, JR Lemaitre, RN Sotoodehnia, N Zieman, SJ Mozaffarian, D Tracy, RP Mukamal, KJ Siscovick, DS AF Djousse, Luc Biggs, Mary L. Ix, Joachim H. Kizer, Jorge R. Lemaitre, Rozenn N. Sotoodehnia, Nona Zieman, Susan J. Mozaffarian, Dariush Tracy, Russell P. Mukamal, Kenneth J. Siscovick, David S. TI Nonesterified Fatty Acids and Risk of Sudden Cardiac Death in Older Adults SO CIRCULATION-ARRHYTHMIA AND ELECTROPHYSIOLOGY LA English DT Article DE epidemiology; sudden death; fatty acids; risk factors ID CARDIOVASCULAR HEALTH; MYOCARDIAL INFARCTION; INSULIN-RESISTANCE; ARRHYTHMIAS; NIDDM; EPIDEMIOLOGY; PATHOGENESIS; METABOLISM AB Background-Although nonesterified fatty acids (NEFA) have been positively associated with coronary heart disease risk factors, limited and inconsistent data are available on the relation between NEFA and sudden cardiac death. Methods and Results-Using a prospective design, we studied 4657 older men and women (mean age, 75 years) from the Cardiovascular Health Study (1992-2006) to evaluate the association between plasma NEFA and the risk of sudden cardiac death in older adults. Plasma concentrations of NEFA were measured using established enzymatic methods, and sudden death was adjudicated using medical records, death certificates, proxy interview, and autopsy reports. We used Cox proportional hazard models to estimate multivariable-adjusted relative risks. During a median follow-up of 10.0 years, 221 new cases of sudden cardiac death occurred. In a multivariable model adjusting for age, sex, race, clinic site, alcohol intake, smoking, prevalent coronary heart disease and heart failure, and self-reported health status, relative risks (95% confidence interval) for sudden cardiac death were 1.0 (ref), 1.15 (0.81-1.64), 1.06 (0.72-1.55), and 0.91 (0.60-1.38) across consecutive quartiles of NEFA concentration. In secondary analyses restricted to the first 5 years of follow-up, we also did not observe a statistically significant association between plasma NEFA and sudden cardiac death. Conclusions-Our data do not provide evidence for an association between plasma NEFA measured late in life and the risk of sudden cardiac death in older adults. (Circ Arrhythm Electrophysiol. 2012;5:273-278.) C1 [Djousse, Luc] Harvard Univ, Sch Med, Brigham & Womens Hosp, Div Aging,Dept Med, Boston, MA 02120 USA. [Djousse, Luc] Boston Vet Affairs Healthcare Syst, Boston, MA USA. [Biggs, Mary L.] Univ Washington, Sch Publ Hlth & Community Med, Dept Biostat, Seattle, WA 98195 USA. [Ix, Joachim H.] Univ Calif San Diego, Dept Med, Div Nephrol, Vet Affairs San Diego Healthcare Syst, San Diego, CA 92103 USA. [Ix, Joachim H.] Univ Calif San Diego, Div Prevent Med, Vet Affairs San Diego Healthcare Syst, San Diego, CA 92103 USA. [Kizer, Jorge R.] Weill Cornell Med Coll, Dept Med, New York, NY USA. [Kizer, Jorge R.] Weill Cornell Med Coll, Dept Publ Hlth, New York, NY USA. [Lemaitre, Rozenn N.; Sotoodehnia, Nona; Siscovick, David S.] Univ Washington, Dept Med, Cardiovasc Hlth Res Unit, Seattle, WA USA. [Zieman, Susan J.] NIA, NIH, Bethesda, MD 20892 USA. [Mozaffarian, Dariush] Brigham & Womens Hosp, Dept Med, Div Cardiovasc Med, Boston, MA 02115 USA. [Djousse, Luc; Mozaffarian, Dariush] Harvard Univ, Sch Med, Boston, MA 02120 USA. [Tracy, Russell P.] Univ Vermont, Coll Med, Dept Pathol, Colchester, VT USA. [Mukamal, Kenneth J.] Beth Israel Deaconess Med Ctr, Dept Gen Med & Primary Care, Boston, MA 02215 USA. [Siscovick, David S.] Univ Washington, Dept Epidemiol, Cardiovasc Hlth Res Unit, Seattle, WA 98195 USA. RP Djousse, L (reprint author), Harvard Univ, Sch Med, Brigham & Womens Hosp, Div Aging,Dept Med, 1620 Tremont St,3rd Floor, Boston, MA 02120 USA. EM ldjousse@rics.bwh.harvard.edu RI Djousse, Luc/F-5033-2017 OI Djousse, Luc/0000-0002-9902-3047 FU National Heart, Lung, and Blood Institute [R01HL094555, N01-HC-85239, N01-HC-85079, N01-HC-85086, N01-HC-35129, N01-HC-15103, N01-HC-55222, N01-HC-75150, N01-HC-45133, HL080295]; National Institute of Neurological Disorders and Stroke (NINDS); National Institute on Aging (NIA) [AG-023629, AG-15928, AG-20098, AG-027058] FX The research reported in this article was supported by the National Heart, Lung, and Blood Institute (R01HL094555) to Drs Djousse, Ix, Mukamal, Zieman, and Kizer. The CHS was supported by contracts N01-HC-85239, N01-HC-85079 through N01-HC-85086, N01-HC-35129, N01-HC-15103, N01-HC-55222, N01-HC-75150, N01-HC-45133, and grant HL080295 from the National Heart, Lung, and Blood Institute, with additional contribution from the National Institute of Neurological Disorders and Stroke (NINDS). Additional support was provided through AG-023629, AG-15928, AG-20098, and AG-027058 from the National Institute on Aging (NIA). A full list of principal CHS investigators and institutions can be found at http://www.chs-nhlbi.org/pi.htm. NR 31 TC 4 Z9 4 U1 1 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1941-3149 J9 CIRC-ARRHYTHMIA ELEC JI Circ.-Arrhythmia Electrophysiol. PD APR PY 2012 VL 5 IS 2 BP 273 EP 278 DI 10.1161/CIRCEP.111.967661 PG 6 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 071HO UT WOS:000313582100016 PM 22281952 ER PT J AU Dettmer, M Alekel, DL Lasrado, JA Messina, M Carriquiry, A Heiberger, K Stewart, JW Franke, W AF Dettmer, Michelle Alekel, D. Lee Lasrado, Joanne A. Messina, Mark Carriquiry, Alicia Heiberger, Kevin Stewart, Jeanne W. Franke, Warren TI The Effect of Soy Protein Beverages on Serum Cell Adhesion Molecule Concentrations in Prehypertensive/Stage 1 Hypertensive Individuals SO JOURNAL OF THE AMERICAN COLLEGE OF NUTRITION LA English DT Article DE cardiovascular disease risk; cell adhesion molecules; ICAM-1; E-selectin; VCAM-1; isoflavones; soy beverages ID VASCULAR ENDOTHELIAL-CELLS; POSTMENOPAUSAL WOMEN; E-SELECTIN; HUMAN ATHEROSCLEROSIS; BLOOD-PRESSURE; CARDIOVASCULAR RISK; INFLAMMATION; ISOFLAVONES; MECHANISMS; VCAM-1 AB Objective: Prehypertensive and hypertensive individuals are at increased risk of atherosclerotic cardiovascular disease (CVD), in part because hypertension contributes to endothelial dysfunction and increased cell adhesion molecule expression. Soy protein and isoflavones may favorably alter CVD risk factors, and hence the aim of this study was to determine whether intake of cow's milk compared with soy beverage prepared from whole soy bean (WSB) or soy protein isolate (SPI) would lower soluble cell adhesion molecule concentrations as a means of decreasing CVD risk. Methods: We enrolled healthy prehypertensive/stage 1 hypertensive men (n = 60; 18-63 years) and premenopausal women (n = 8; 20-48 years). Participants were randomized to 1 of 3 groups for 8 weeks: cow's milk (600 mL/d), SPI beverage (840 mL/d; 30.1 mg total isoflavones/d), or WSB beverage (840 mL/d; 91.4 mg total isoflavones/d). We measured soluble vascular cell adhesion molecule-1 (VCAM-1), intercellular cell adhesion molecule-1 (ICAM-1), and endothelial-leukocyte adhesion molecule-1 (E-selectin) concentrations at baseline and week 8. Results: Soluble CAM concentrations were not altered by treatment and did not differ between prehypertensive and hypertensive participants. However, analysis of variance indicated a treatment X gender interaction (gender effect) for ICAM-1 (p = 0.0037) but not for E-selectin (p = 0.067) or VCAM-1 (p = 0.16). Men had higher concentrations of ICAM-1 and E-selectin, respectively, at baseline (p = 0.0071, p = 0.049) and week 8 (p = 0.0054, p = 0.038) than women did. Conclusion: Neither intake of cow's milk nor soy beverage for 8 weeks altered soluble CAM concentrations in prehypertensive/stage 1 hypertensive individuals, suggesting that neither type of beverage diminished atherosclerotic CVD risk in mildly hypertensive individuals by way of improving circulating CAM concentrations. C1 [Dettmer, Michelle; Alekel, D. Lee] Iowa State Univ, Dept Food Sci & Human Nutr, Ames, IA USA. [Dettmer, Michelle; Alekel, D. Lee; Lasrado, Joanne A.; Heiberger, Kevin; Stewart, Jeanne W.] Iowa State Univ, Nutr & Wellness Res Ctr, Ames, IA USA. [Carriquiry, Alicia] Iowa State Univ, Dept Stat, Ames, IA USA. [Franke, Warren] Iowa State Univ, Dept Kinesiol, Ames, IA USA. [Messina, Mark] Loma Linda Univ, Sch Publ Hlth, Dept Nutr, Port Townsend, WA USA. [Heiberger, Kevin] Univ N Texas, Athlet Dept, Denton, TX 76203 USA. RP Alekel, DL (reprint author), NIH, NCCAM, 6707 Democracy Blvd,Suite 401, Bethesda, MD 20892 USA. EM Lee.Alekel@nih.gov FU Soyfoods Council; Iowa Soybean Association; WhiteWave Foods Company FX The Soyfoods Council and Iowa Soybean Association provided most of the funding for this intervention; WhiteWave Foods Company also contributed funds and soy milk product; Fareway Stores, Inc. also provided milk product. We acknowledge Linda Funk, executive director of The Soyfoods Council, and the Iowa Soybean Association, for their contribution to this study. We thank our participants who diligently adhered to the dietary intervention and reported faithfully to our research unit. We are grateful to the dietetics students (particularly Abby Pollard, Heather Meardon Plizga, and Tiffany McCabe) in the Department of Food Science and Human Nutrition at Iowa State University who helped with lab processing, data collection, dietary intake analysis, and data entry. We thank Dennis Lock, a doctoral student in the Department of Statistics at Iowa State University, for his efforts with data analysis. NR 31 TC 0 Z9 0 U1 1 U2 5 PU AMER COLLEGE NUTRITION PI CLEARWATER PA 300 SOUTH DUNCAN AVENUE, STE 225, CLEARWATER, FL 33755 USA SN 0731-5724 J9 J AM COLL NUTR JI J. Am. Coll. Nutr. PD APR PY 2012 VL 31 IS 2 BP 100 EP 110 PG 11 WC Nutrition & Dietetics SC Nutrition & Dietetics GA 069XL UT WOS:000313470300005 PM 22855915 ER PT J AU Drake, JW AF Drake, John W. TI Contrasting Mutation Rates from Specific-Locus and Long-Term Mutation-Accumulation Procedures SO G3-GENES GENOMES GENETICS LA English DT Article DE specific-locus mutation rates; genomic sequencing for mutation rates; synonymous codons; neutral mutations ID CODON USAGE BIAS; DNA-POLYMERASE; FIDELITY AB Until recently, the two predominant ways to estimate mutation rates were the specific-locus method and the mutation-accumulation (Bateman-Mukai) method. Both involve seeding a number of parallel lines from a small, genetically uniform population, growing as long as is feasible but not so long as to allow selection to perturb mutant frequencies, and sometimes using extreme bottlenecks to facilitate the retention of deleterious mutations. In the specific-locus method, mutations are selected according to their specific phenotypes and are confirmed by sequencing. In older versions of the mutation-accumulation method, the increase in variance of a quantitative fitness trait is measured and converted into a mutation rate. More recently, a variation on the mutation-accumulation method has become possible based on phenotype-blind genomic sequencing, which might (or might not) provide improved sampling breadth, usually at the expense of sample size. In a recent study, genomic sequencing was applied to Escherichia coli lines propagated for 40,000 generations and passaged daily via 5,000,000 cells. To mitigate the impact of selection, the only targets employed for rate calculations were putatively neutral synonymous mutations. The mutation rate estimate was about 6-fold lower than obtained previously with a robust specific-locus method. Here I argue that purifying selection acting to shape the strong codon preferences of E. coli is the probable cause of the lower estimate, rather than, for instance, a lower mutation rate in nature than in the laboratory. C1 NIEHS, Mol Genet Lab, Res Triangle Pk, NC 27709 USA. RP Drake, JW (reprint author), NIEHS, Mol Genet Lab, 111 TW Alexander Dr, Res Triangle Pk, NC 27709 USA. EM drake@niesh.nih.gov FU Intramural Research Program of the NIH, National Institute of Environmental Health Sciences [Z01ES065016] FX I thank Libertad Garcia-Villada for running the G tests and both her and Shay Covo for comments on the presubmission draft of this paper. This research was supported by funds allocated to project Z01ES065016 of the Intramural Research Program of the NIH, National Institute of Environmental Health Sciences. NR 15 TC 5 Z9 5 U1 0 U2 13 PU GENETICS SOC AM PI BETHESDA PA 9650 ROCKVILLE AVE, BETHESDA, MD 20814 USA SN 2160-1836 J9 G3-GENES GENOM GENET JI G3-Genes Genomes Genet. PD APR 1 PY 2012 VL 2 IS 4 BP 483 EP 485 DI 10.1534/g3.111.001842 PG 3 WC Genetics & Heredity SC Genetics & Heredity GA 055YD UT WOS:000312453000008 PM 22540039 ER PT J AU Liu, QY Spusta, SC Mi, RF Lassiter, RNT Stark, MR Hoke, A Rao, MS Zeng, XM AF Liu, Qiuyue Spusta, Steven C. Mi, Ruifa Lassiter, Rhonda N. T. Stark, Michael R. Hoeke, Ahmet Rao, Mahendra S. Zeng, Xianmin TI Human Neural Crest Stem Cells Derived from Human ESCs and Induced Pluripotent Stem Cells: Induction, Maintenance, and Differentiation into Functional Schwann Cells SO STEM CELLS TRANSLATIONAL MEDICINE LA English DT Article DE Neural crest; Human embryonic stem cells; Differentiation; Schwann cells; Peripheral neuron ID DOPAMINERGIC-NEURONS; DEFINED CONDITIONS; NERVOUS-SYSTEM; SKULL VAULT; FATE; DERIVATION; EXPRESSION; GENERATION; PATIENT; DISEASE AB The neural crest (NC) is a transient, multipotent, migratory cell population unique to vertebrates that gives rise to diverse cell lineages. Much of our knowledge of NC development comes from studies of organisms such as chicken and zebrafish because human NC is difficult to obtain because of its transient nature and the limited availability of human fetal cells. Here we examined the process of NC induction from human pluripotent stem cells, including human embryonic stem cells (hESCs) and induced pluripotent stem cells (iPSCs). We showed that NC cells could be efficiently induced from hESCs by a combination of growth factors in medium conditioned on stromal cells and that NC stem cells (NCSCs) could be purified by p75 using fluorescence-activated cell sorting (FACS). FACS-isolated NCSCs could be propagated in vitro in five passages and cryopreserved while maintaining NCSC identity characterized by the expression of a panel of NC markers such as p75, Sox9, Sox10, CD44, and HNK1. In vitro-expanded NCSCs were able to differentiate into neurons and glia (Schwann cells) of the peripheral nervous system, as well as mesenchymal derivatives. hESC-derived NCSCs appeared to behave similarly to endogenous embryonic NC cells when injected in chicken embryos. Using a defined medium, we were able to generate and propagate a nearly pure population of Schwann cells that uniformly expressed glial fibrillary acidic protein, 5100, and p75. Schwann cells generated by our protocol myelinated rat dorsal root ganglia neurons in vitro. To our knowledge, this is the first report on myelination by hESC- or iPSC-derived Schwann cells. STEM CELLS TRANSLATIONAL MEDICINE 2012;1:266-278 C1 [Liu, Qiuyue; Spusta, Steven C.; Rao, Mahendra S.; Zeng, Xianmin] Buck Inst Res Aging, Novato, CA 94945 USA. [Mi, Ruifa; Hoeke, Ahmet] Johns Hopkins Univ, Sch Med, Dept Neurol, Baltimore, MD 21205 USA. [Mi, Ruifa; Hoeke, Ahmet] Johns Hopkins Univ, Sch Med, Dept Neurosci, Baltimore, MD 21205 USA. [Lassiter, Rhonda N. T.; Stark, Michael R.] Brigham Young Univ, Dept Physiol, Provo, UT 84602 USA. [Lassiter, Rhonda N. T.; Stark, Michael R.] Brigham Young Univ, Dept Dev Biol, Provo, UT 84602 USA. [Rao, Mahendra S.] NIH, Natl Ctr Regenerat Med, Bethesda, MD 20892 USA. RP Zeng, XM (reprint author), Buck Inst Res Aging, Novato, CA 94945 USA. EM xzeng@buckinstitute.org OI Hoke, Ahmet/0000-0003-1215-3373 FU California Institute for Regenerative Medicine [CL1-00501-1, TG2-01155]; Maryland Stem Cell Research Fund Grant [302385] FX This work was supported in part by the California Institute for Regenerative Medicine Grants CL1-00501-1 (to X.Z.) and TG2-01155 (to X.Z.) and Maryland Stem Cell Research Fund Grant 302385 (to A.H.). We thank Dr. L. Cheng at the Johns Hopkins University for providing the iPSC line and Drs. J. Peng and A. Swistowski (a previous member of our laboratory) for technical assistance. We also acknowledge the Developmental Studies Hybridoma Bank maintained by the University of Iowa (Iowa City, IA) for supply of monoclonal antibodies. NR 54 TC 40 Z9 45 U1 0 U2 16 PU ALPHAMED PRESS PI DURHAM PA 318 BLACKWELL ST, STE 260, DURHAM, NC 27701-2884 USA SN 2157-6564 J9 STEM CELL TRANSL MED JI Stem Cells Transl. Med. PD APR PY 2012 VL 1 IS 4 BP 266 EP 278 DI 10.5966/sctm.2011-0042 PG 13 WC Cell & Tissue Engineering SC Cell Biology GA 057NZ UT WOS:000312571600007 PM 23197806 ER PT J AU Saphire, EO Feldmann, H AF Saphire, Erica Ollmann Feldmann, Heinz TI Untitled SO CURRENT OPINION IN VIROLOGY LA English DT Editorial Material C1 [Saphire, Erica Ollmann] Scripps Res Inst, Dept Immunol & Microbial Sci, La Jolla, CA 92037 USA. [Feldmann, Heinz] NIAID, Virol Lab, DIR, NIH,Rocky Mt Labs, Hamilton, MT 59840 USA. RP Saphire, EO (reprint author), Scripps Res Inst, Dept Immunol & Microbial Sci, 10550 N Torrey Pines Rd,IMM-21, La Jolla, CA 92037 USA. EM erica@scripps.edu NR 0 TC 0 Z9 0 U1 0 U2 4 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 1879-6257 J9 CURR OPIN VIROL JI Curr. Opin. Virol. PD APR PY 2012 VL 2 IS 2 BP 157 EP 159 DI 10.1016/j.coviro.2012.03.002 PG 3 WC Virology SC Virology GA 051FX UT WOS:000312112700008 PM 22482713 ER PT J AU Pierson, TC Diamond, MS AF Pierson, Theodore C. Diamond, Michael S. TI Degrees of maturity: the complex structure and biology of flaviviruses SO CURRENT OPINION IN VIROLOGY LA English DT Article ID TICK-BORNE ENCEPHALITIS; WEST-NILE-VIRUS; ENVELOPE PROTEIN-E; ANTIBODY-MEDIATED NEUTRALIZATION; CROSS-REACTIVE ANTIBODIES; FUSION-LOOP ANTIBODY; DENGUE VIRUS; MONOCLONAL-ANTIBODIES; ENDOPLASMIC-RETICULUM; MEMBRANE-FUSION AB Flaviviruses are small enveloped virions that enter target cells in a pH-dependent fashion. Virus attachment, entry, and membrane fusion are orchestrated by the envelope (E) and pre-membrane (prM) proteins, the two structural proteins displayed on the surface of virions. Flaviviruses assemble as an immature non-infectious form onto which prM and E form trimeric spikes. During egress from infected cells, flaviviruses undergo dramatic structural changes characterized by the formation of a herringbone arrangement of E proteins that lie flat against the surface of the virion and cleavage of the prM protein by the cellular protease furin. The result is a relatively smooth, infectious mature virion. This dynamic process is now understood in structural detail at the atomic level. However, recent studies indicate that many of the virions released from cells share structural features of both immature and mature virus particles. These mosaic partially mature virions are infectious and interact uniquely with target cells and the host immune response. Here, we will discuss recent advances in our understanding of the biology and significance of partially mature flaviviruses. C1 [Pierson, Theodore C.] NIAID, Viral Pathogenesis Sect, Viral Dis Lab, NIH, Bethesda, MD 20892 USA. [Diamond, Michael S.] Washington Univ, Sch Med, Dept Med, St Louis, MO 63110 USA. [Diamond, Michael S.] Washington Univ, Sch Med, Dept Mol Microbiol, St Louis, MO 63110 USA. [Diamond, Michael S.] Washington Univ, Sch Med, Dept Pathol & Immunol, St Louis, MO USA. RP Pierson, TC (reprint author), NIAID, Viral Pathogenesis Sect, Viral Dis Lab, NIH, Bethesda, MD 20892 USA. EM piersontc@mail.nih.gov FU Intramural Research Program of the NIH, National Institutes of Allergy and Infectious Diseases (NIAID) [R01-AI077955, U01-AI061373] FX This work was supported by the Intramural Research Program of the NIH, National Institutes of Allergy and Infectious Diseases (NIAID), R01-AI077955 and U01-AI061373. The authors thank Mr. Ethan Tyler and Phong Lee for preparation of the figures. We are grateful to Drs. Kimberly Dowd and Swati Mukherjee for their thoughtful comments on our manuscript. We thank members of our laboratory for useful discussions. NR 68 TC 48 Z9 50 U1 2 U2 12 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 1879-6257 J9 CURR OPIN VIROL JI Curr. Opin. Virol. PD APR PY 2012 VL 2 IS 2 BP 168 EP 175 DI 10.1016/j.coviro.2012.02.011 PG 8 WC Virology SC Virology GA 051FX UT WOS:000312112700010 PM 22445964 ER PT J AU Yang, SC Karne, NK Goff, SL Black, MA Xu, H Bischof, D Cornetta, K Rosenberg, SA Morgan, RA Feldman, SA AF Yang, Shicheng Karne, Neel K. Goff, Stephanie L. Black, Mary A. Xu, Hui Bischof, Daniela Cornetta, Kenneth Rosenberg, Steven A. Morgan, Richard A. Feldman, Steven A. TI A Simple and Effective Method to Generate Lentiviral Vectors for Ex Vivo Gene Delivery to Mature Human Peripheral Blood Lymphocytes SO HUMAN GENE THERAPY METHODS LA English DT Article ID SEVERE COMBINED IMMUNODEFICIENCY; TUMOR-INFILTRATING LYMPHOCYTES; T-CELLS; TRANSGENE EXPRESSION; RETROVIRAL VECTORS; CANCER REGRESSION; STEM-CELLS; THERAPY; VIRUS; TRANSFECTION AB Human ex vivo gene therapy protocols have been used successfully to treat a variety of genetic disorders, infectious diseases, and cancer. Murine oncoretroviruses (specifically, gammaretroviruses) have served as the primary gene delivery vehicles for these trials. However, in some cases, such vectors have been associated with insertional mutagenesis. As a result, alternative vector platforms such as lentiviral vectors (LVVs) are being developed. LVVs may provide advantages compared with gammaretroviral vectors, including the ability to transduce large numbers of nondividing cells, resistance to gene silencing, and a potentially safer integration profile. The aim of this study was to develop a simplified process for the rapid production of clinical-grade LVVs. To that end, we used a self-inactivating bicistronic LVV encoding an MART (melanoma antigen recognized by T cells)-1-reactive T cell receptor containing oPRE, an optimized and truncated version of woodchuck hepatitis virus posttranslational regulatory element (wPRE). Using our simplified clinical production process, 293T cells were transiently transfected in roller bottles. The LVV supernatant was collected, treated with Benzonase, and clarified by modified step filtration. LVV produced in this manner exhibited titers and a biosafety profile similar to those of cGMP (current Good Manufacturing Practices) LVVs previously manufactured at the Indiana University Vector Production Facility in support of a phase I/II clinical trial. We describe a simple, efficient, and low-cost method for the production of clinical-grade LVV for ex vivo gene therapy protocols. C1 [Yang, Shicheng; Karne, Neel K.; Goff, Stephanie L.; Black, Mary A.; Xu, Hui; Rosenberg, Steven A.; Morgan, Richard A.; Feldman, Steven A.] NCI, Surg Branch, NIH, Bethesda, MD 20892 USA. [Karne, Neel K.] SUNY Upstate Med Univ, Dept Surg Gen Surg, Syracuse, NY 13210 USA. [Goff, Stephanie L.] Columbia Univ, Coll Phys & Surg, Dept Surg, New York, NY 10032 USA. [Bischof, Daniela; Cornetta, Kenneth] Indiana Univ Sch Med, Dept Med & Mol Genet, Indianapolis, IN 46202 USA. [Cornetta, Kenneth] Indiana Univ Sch Med, Dept Microbiol & Immunol, Indianapolis, IN 46202 USA. [Cornetta, Kenneth] Indiana Univ Sch Med, Dept Med, Indianapolis, IN 46202 USA. RP Feldman, SA (reprint author), NCI, Surg Branch, NIH, Bldg 10, Bethesda, MD 20892 USA. EM feldmanst@mail.nih.gov FU NCRR NIH HHS [P40 RR024928]; PHS HHS [HHSN26820074820] NR 56 TC 3 Z9 3 U1 1 U2 2 PU MARY ANN LIEBERT INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1946-6536 J9 HUM GENE THER METHOD JI Hum. Gene Ther. Methods PD APR PY 2012 VL 23 IS 2 BP 73 EP 83 DI 10.1089/hgtb.2011.199 PG 11 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine, Research & Experimental SC Biotechnology & Applied Microbiology; Genetics & Heredity; Research & Experimental Medicine GA 022WM UT WOS:000309994900001 PM 22515320 ER PT J AU Carty, CL Buzkova, P Fornage, M Franceschini, N Cole, S Heiss, G Hindorff, LA Howard, BV Mann, S Martin, LW Zhang, Y Matise, TC Prentice, R Reiner, AP Kooperberg, C AF Carty, Cara L. Buzkova, Petra Fornage, Myriam Franceschini, Nora Cole, Shelley Heiss, Gerardo Hindorff, Lucia A. Howard, Barbara V. Mann, Sue Martin, Lisa W. Zhang, Ying Matise, Tara C. Prentice, Ross Reiner, Alexander P. Kooperberg, Charles TI Associations Between Incident Ischemic Stroke Events and Stroke and Cardiovascular Disease-Related Genome-Wide Association Studies Single Nucleotide Polymorphisms in the Population Architecture Using Genomics and Epidemiology Study SO CIRCULATION-CARDIOVASCULAR GENETICS LA English DT Article DE genetics of stroke; risk factors for stroke; genetics of cardiovascular disease; cohort studies ID ATHEROSCLEROSIS RISK; FOLLOW-UP; DESIGN; METAANALYSIS; HEALTH; VARIANTS; SURVIVAL; TRAITS AB Background-Genome-wide association studies (GWAS) have identified loci associated with ischemic stroke (IS) and cardiovascular disease (CVD) in European-descent individuals, but their replication in different populations has been largely unexplored. Methods and Results-Nine single nucleotide polymorphisms (SNPs) selected from GWAS and meta-analyses of stroke, and 86 SNPs previously associated with myocardial infarction and CVD risk factors, including blood lipids (high density lipoprotein [HDL], low density lipoprotein [LDL], and triglycerides), type 2 diabetes, and body mass index (BMI), were investigated for associations with incident IS in European Americans (EA) N=26 276, African-Americans (AA) N=8970, and American Indians (AI) N=3570 from the Population Architecture using Genomics and Epidemiology Study. Ancestry-specific fixed effects meta-analysis with inverse variance weighting was used to combine study-specific log hazard ratios from Cox proportional hazards models. Two of 9 stroke SNPs (rs783396 and rs1804689) were associated with increased IS hazard in AA; none were significant in this large EA cohort. Of 73 CVD risk factor SNPs tested in EA, 2 (HDL and triglycerides SNPs) were associated with IS. In AA, SNPs associated with LDL, HDL, and BMI were significantly associated with IS (3 of 86 SNPs tested). Out of 58 SNPs tested in AI, 1 LDL SNP was significantly associated with IS. Conclusions-Our analyses showing lack of replication in spite of reasonable power for many stroke SNPs and differing results by ancestry highlight the need to follow up on GWAS findings and conduct genetic association studies in diverse populations. We found modest IS associations with BMI and lipids SNPs, though these findings require confirmation. (Circ Cardiovasc Genet. 2012;5:210-216.) C1 [Carty, Cara L.; Mann, Sue; Prentice, Ross; Kooperberg, Charles] Fred Hutchinson Canc Res Ctr, Seattle, WA 98109 USA. [Buzkova, Petra] Univ Washington, Dept Biostat, Seattle, WA 98195 USA. [Fornage, Myriam] Univ Texas Hlth Sci Ctr Houston, Inst Mol Med, Houston, TX USA. [Fornage, Myriam] Univ Texas Hlth Sci Ctr Houston, Sch Publ Hlth, Div Epidemiol, Houston, TX USA. [Franceschini, Nora; Heiss, Gerardo] Univ N Carolina, Dept Epidemiol, Chapel Hill, NC USA. [Cole, Shelley] Texas Biomed Res Inst, Dept Genet, San Antonio, TX USA. [Hindorff, Lucia A.] NHGRI, Off Populat Genom, Bethesda, MD 20892 USA. [Howard, Barbara V.] Medstar Hlth Res Inst, Washington, DC USA. [Howard, Barbara V.; Martin, Lisa W.] George Washington Univ, Sch Med, Washington, DC USA. [Zhang, Ying] Univ Oklahoma, Hlth Sci Ctr, Oklahoma City, OK USA. [Matise, Tara C.] Rutgers State Univ, Dept Genet, Piscataway, NJ USA. [Reiner, Alexander P.] Univ Washington, Dept Epidemiol, Seattle, WA 98195 USA. RP Carty, CL (reprint author), Fred Hutchinson Canc Res Ctr, 1100 Fairview Ave N,M3-A410, Seattle, WA 98109 USA. EM ccarty@fhcrc.org RI Carty, Cara/B-8683-2013; OI Martin, Lisa Warsinger/0000-0003-4352-0914 FU National Human Genome Research Institute (NHGRI); CALiCo [U01HG004803]; EAGLE [U01HG004798]; MEC [U01HG004802]; WHI [U01HG004790]; Coordinating Center [U01HG004801]; NHGRI PAGE program [U01HG004798-01]; Johns Hopkins University from NHLBI [N01-HV-48195]; Centers for Disease Control and Prevention; National Cancer Institute [R37CA54281, R01 CA63, P01CA33619, U01CA136792, U01CA98758] FX The Population Architecture Using Genomics and Epidemiology (PAGE) program is funded by the National Human Genome Research Institute (NHGRI), supported by U01HG004803 (CALiCo), U01HG004798 (EAGLE), U01HG004802 (MEC), U01HG004790 (WHI), and U01HG004801 (Coordinating Center), and their respective NHGRI ARRA supplements. The contents of this paper are solely the responsibility of the authors and do not necessarily represent the official views of the NIH.; The "Epidemiologic Architecture for Genes Linked to Environment (EAGLE)" is funded through the NHGRI PAGE program (U01HG004798-01 and its NHGRI ARRA supplement). Genotyping services for select NHANES III SNPs presented here were also provided by the Johns Hopkins University under federal contract number (N01-HV-48195) from NHLBI. The study participants derive from the National Health and Nutrition Examination Surveys (NHANES), and these studies are supported by the Centers for Disease Control and Prevention. The findings and conclusions in this report are those of the authors and do not necessarily represent the views of the Centers for Disease Control and Prevention.; The Multiethnic Cohort study (MEC) characterization of epidemiological architecture is funded through the NHGRI PAGE program (U01HG004802 and its NHGRI ARRA supplement). The MEC study is funded through the National Cancer Institute (R37CA54281, R01 CA63, P01CA33619, U01CA136792, and U01CA98758). NR 37 TC 8 Z9 10 U1 0 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1942-325X J9 CIRC-CARDIOVASC GENE JI Circ.-Cardiovasc. Genet. PD APR PY 2012 VL 5 IS 2 BP 210 EP 216 DI 10.1161/CIRCGENETICS.111.962191 PG 7 WC Cardiac & Cardiovascular Systems; Genetics & Heredity SC Cardiovascular System & Cardiology; Genetics & Heredity GA 021KS UT WOS:000309884300011 PM 22403240 ER PT J AU Kristiansson, K Perola, M Tikkanen, E Kettunen, J Surakka, I Havulinna, AS Stancakova, A Barnes, C Widen, E Kajantie, E Eriksson, JG Viikari, J Kahonen, M Lehtimoki, T Raitakari, OT Hartikainen, AL Ruokonen, A Pouta, A Jula, A Kangas, AJ Soininen, P Ala-Korpela, M Mannisto, S Jousilahti, P Bonnycastle, LL Jarvelin, MR Kuusisto, J Collins, FS Laakso, M Hurles, ME Palotie, A Peltonen, L Ripatti, S Salomaa, V AF Kristiansson, Kati Perola, Markus Tikkanen, Emmi Kettunen, Johannes Surakka, Ida Havulinna, Aki S. Stancakova, Alena Barnes, Chris Widen, Elisabeth Kajantie, Eero Eriksson, Johan G. Viikari, Jorma Kahonen, Mika Lehtimaki, Terho Raitakari, Olli T. Hartikainen, Anna-Liisa Ruokonen, Aimo Pouta, Anneli Jula, Antti Kangas, Antti J. Soininen, Pasi Ala-Korpela, Mika Mannisto, Satu Jousilahti, Pekka Bonnycastle, Lori L. Jarvelin, Marjo-Riitta Kuusisto, Johanna Collins, Francis S. Laakso, Markku Hurles, Matthew E. Palotie, Aarno Peltonen, Leena Ripatti, Samuli Salomaa, Veikko TI Genome-Wide Screen for Metabolic Syndrome Susceptibility Loci Reveals Strong Lipid Gene Contribution But No Evidence for Common Genetic Basis for Clustering of Metabolic Syndrome Traits SO CIRCULATION-CARDIOVASCULAR GENETICS LA English DT Article DE metabolic syndrome; risk factors; genome-wide association study; meta-analysis; lipids ID ASSOCIATION ANALYSIS; RISK; INSULIN; COMPONENTS; OBESITY AB Background-Genome-wide association (GWA) studies have identified several susceptibility loci for metabolic syndrome (MetS) component traits, but have had variable success in identifying susceptibility loci to the syndrome as an entity. We conducted a GWA study on MetS and its component traits in 4 Finnish cohorts consisting of 2637 MetS cases and 7927 controls, both free of diabetes, and followed the top loci in an independent sample with transcriptome and nuclear magnetic resonance-based metabonomics data. Furthermore, we tested for loci associated with multiple MetS component traits using factor analysis, and built a genetic risk score for MetS. Methods and Results-A previously known lipid locus, APOA1/C3/A4/A5 gene cluster region (SNP rs964184), was associated with MetS in all 4 study samples (P=7.23x10(-9) in meta-analysis). The association was further supported by serum metabolite analysis, where rs964184 was associated with various very low density lipoprotein, triglyceride, and high-density lipoprotein metabolites (P=0.024-1.88x10(-5)). Twenty-two previously identified susceptibility loci for individual MetS component traits were replicated in our GWA and factor analysis. Most of these were associated with lipid phenotypes, and none with 2 or more uncorrelated MetS components. A genetic risk score, calculated as the number of risk alleles in loci associated with individual MetS traits, was strongly associated with MetS status. Conclusions-Our findings suggest that genes from lipid metabolism pathways have the key role in the genetic background of MetS. We found little evidence for pleiotropy linking dyslipidemia and obesity to the other MetS component traits, such as hypertension and glucose intolerance. (Circ Cardiovasc Genet. 2012;5:242-249.) C1 [Kristiansson, Kati; Perola, Markus; Tikkanen, Emmi; Kettunen, Johannes; Surakka, Ida; Ripatti, Samuli] Univ Helsinki, Publ Hlth Genom Unit, Helsinki, Finland. [Havulinna, Aki S.; Mannisto, Satu; Jousilahti, Pekka; Salomaa, Veikko] Univ Helsinki, Chron Dis Epidemiol & Prevent Unit, Helsinki, Finland. [Kajantie, Eero; Eriksson, Johan G.] Univ Helsinki, Diabet Prevent Unit, Dept Chron Dis Prevent, Helsinki, Finland. [Jousilahti, Pekka] Univ Helsinki, Int Affairs Unit, Natl Inst Hlth & Welf, Helsinki, Finland. [Kristiansson, Kati; Perola, Markus; Tikkanen, Emmi; Kettunen, Johannes; Surakka, Ida; Widen, Elisabeth; Pouta, Anneli; Ripatti, Samuli] Univ Helsinki, Inst Mol Med Finland FIMM, Helsinki, Finland. [Eriksson, Johan G.] Univ Helsinki, Dept Gen Practice & Primary Hlth Care, Helsinki, Finland. [Perola, Markus] Univ Tartu, Estonian Genome Ctr, EE-50090 Tartu, Estonia. [Stancakova, Alena] Univ Eastern Finland, Inst Clin Med, Dept Med, Kuopio, Finland. [Barnes, Chris] Univ London Imperial Coll Sci Technol & Med, Ctr Bioinformat, Div Mol Biosci, London, England. [Barnes, Chris] Univ London Imperial Coll Sci Technol & Med, Inst Math Sci, London, England. [Jarvelin, Marjo-Riitta] Univ London Imperial Coll Sci Technol & Med, Fac Med, Sch Publ Hlth, Dept Epidemiol & Biostat, London, England. [Kajantie, Eero] Univ Helsinki, Helsinki, Finland. [Kajantie, Eero] Univ Helsinki, Cent Hosp, Hosp Children & Adolescents, Helsinki, Finland. [Eriksson, Johan G.] Univ Helsinki, Cent Hosp, Unit Gen Practice, Helsinki, Finland. [Eriksson, Johan G.] Folkhalsan Res Ctr, Helsinki, Finland. [Eriksson, Johan G.] Vaasa Cent Hosp, Vaasa, Finland. [Raitakari, Olli T.] Turku Univ Hosp, FIN-20520 Turku, Finland. [Raitakari, Olli T.] Univ Turku, Res Ctr Appl & Prevent Cardiovasc Med, Turku, Finland. [Viikari, Jorma] Univ Turku, Dept Med, Turku, Finland. [Kahonen, Mika] Univ Tampere, Dept Clin Physiol, FIN-33101 Tampere, Finland. [Lehtimaki, Terho] Univ Tampere, Dept Clin Chem, FIN-33101 Tampere, Finland. [Lehtimaki, Terho] Tampere Univ Hosp, Tampere, Finland. [Hartikainen, Anna-Liisa] Univ Oulu, Inst Clin Med Obstet & Gynaecol, Oulu, Finland. [Ruokonen, Aimo] Univ Oulu, Dept Clin Chem, Oulu, Finland. [Pouta, Anneli; Jarvelin, Marjo-Riitta] Natl Inst Hlth & Welf, Dept Children Young People & Families, Oulu, Finland. [Jula, Antti] Natl Inst Hlth & Welf, Dept Chron Dis Prevent, Populat Studies Unit, Turku, Finland. [Kangas, Antti J.; Soininen, Pasi; Ala-Korpela, Mika] Univ Oulu, Computat Med Res Grp, Inst Clin Med, Oulu, Finland. [Ala-Korpela, Mika] Univ Oulu, Dept Internal Med, Clin Res Ctr, SF-90220 Oulu, Finland. [Jarvelin, Marjo-Riitta] Univ Oulu, Inst Hlth Sci, Oulu, Finland. [Jarvelin, Marjo-Riitta] Univ Oulu, Bioctr Oulu, Oulu, Finland. [Soininen, Pasi; Ala-Korpela, Mika] Univ Eastern Finland, Dept Biosci, Chem Lab, NMR Metabon Lab, Kuopio, Finland. [Bonnycastle, Lori L.; Collins, Francis S.] NHGRI, NIH, Bethesda, MD 20892 USA. [Kuusisto, Johanna; Collins, Francis S.] Kuopio Univ Hosp, SF-70210 Kuopio, Finland. [Kuusisto, Johanna; Collins, Francis S.] Univ Eastern Finland, Inst Clin Med, Dept Med, Kuopio, Finland. [Hurles, Matthew E.; Palotie, Aarno; Ripatti, Samuli] Wellcome Trust Sanger Inst, Cambridge, England. [Palotie, Aarno] Broad Inst & Harvard, Program Med & Populat Genet & Genet Anal Platform, Cambridge, MA USA. [Palotie, Aarno] Univ Cent Hosp, Helsinki, Finland. [Palotie, Aarno] Univ Helsinki, Dept Med Genet, Helsinki, Finland. RP Kristiansson, K (reprint author), Univ Helsinki, Natl Inst Hlth & Welf, PL 104, FI-00251 Helsinki, Finland. EM kati.kristiansson@thl.fi RI Ripatti, Samuli/H-9446-2014; OI Ripatti, Samuli/0000-0002-0504-1202; Jarvelin, Marjo-Riitta/0000-0002-2149-0630; Eriksson, Johan/0000-0002-2516-2060; Kristiansson, Kati/0000-0003-4688-107X; Mannisto, Satu/0000-0002-8668-3046; Barnes, Chris/0000-0002-9459-1395 FU European Community's Seventh Framework Programme, BioSHaRE Consortium [261433]; Academy of Finland; Orion-Farmos Research Foundation; Finnish Foundation for Cardiovascular Research; Sigrid Juselius Foundation; Diabetes Research Foundation; Finnish Foundation for Pediatric Research; Novo Nordisk Foundation; Jenny and Antti Wihuri Foundation; Biotechnology and Biological Research Council; Wellcome Trust; Finnish Diabetes Research Society; Samfundet Folkhalsan; Juho Vainio Foundation; Finska Lakaresallskapet; Paivikki and Sakari Sohlberg Foundation; Signe and Ane Gyllenberg Foundation; Yrjo Jahnsson Foundation; Social Insurance Institution of Finland; University Hospital Medical; Emil Aaltonen Foundation; University Hospital Oulu, Biocenter; University of Oulu; NHLBI; ENGAGE; Medical Research Council; Biocentrum Helsinki FX This research was supported through funds from the European Community's Seventh Framework Programme (FP7/2007-2013), BioSHaRE Consortium, grant agreement 261433, Academy of Finland, Orion-Farmos Research Foundation, Finnish Foundation for Cardiovascular Research, Sigrid Juselius Foundation, Diabetes Research Foundation, Finnish Foundation for Pediatric Research, Novo Nordisk Foundation, Jenny and Antti Wihuri Foundation, Biotechnology and Biological Research Council, Wellcome Trust, Finnish Diabetes Research Society, Samfundet Folkhalsan, Juho Vainio Foundation, Finska Lakaresallskapet, Paivikki and Sakari Sohlberg Foundation, Signe and Ane Gyllenberg Foundation, Yrjo Jahnsson Foundation, Social Insurance Institution of Finland, University Hospital Medical funds to Tampere and Turku University Hospitals, Emil Aaltonen Foundation, University Hospital Oulu, Biocenter, University of Oulu, NHLBI, ENGAGE, Medical Research Council, and Biocentrum Helsinki (see online-only Data Supplement). NR 34 TC 79 Z9 82 U1 0 U2 23 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1942-325X J9 CIRC-CARDIOVASC GENE JI Circ.-Cardiovasc. Genet. PD APR PY 2012 VL 5 IS 2 BP 242 EP 249 DI 10.1161/CIRCGENETICS.111.961482 PG 8 WC Cardiac & Cardiovascular Systems; Genetics & Heredity SC Cardiovascular System & Cardiology; Genetics & Heredity GA 021KS UT WOS:000309884300015 PM 22399527 ER PT J AU Abdelazim, SA Bachran, C David, A Leppla, SH AF Abdelazim, Suzanne Aly Bachran, Christopher David, Alexandre Leppla, Stephen H. TI A non-radioactive high-throughput assay for the detection of cellular protein synthesis SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology Meeting CY APR 21-25, 2012 CL San Diego, CA C1 [Abdelazim, Suzanne Aly; Bachran, Christopher; David, Alexandre; Leppla, Stephen H.] NIAID, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR PY 2012 VL 26 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 032IZ UT WOS:000310711305936 ER PT J AU Adelman, KL AF Adelman, Karen L. TI Probing the dynamics of promoter proximally paused Pol II SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology Meeting CY APR 21-25, 2012 CL San Diego, CA C1 [Adelman, Karen L.] NIEHS, Mol Carcinogenesis Lab, Res Triangle Pk, NC 27709 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR PY 2012 VL 26 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 032IZ UT WOS:000310711300166 ER PT J AU Ahuja, JKC Bhagwat, S Haytowitz, D Holden, J Bailey, R Dwyer, J Milner, J Moshfegh, A AF Ahuja, Jaspreet K. C. Bhagwat, Seema Haytowitz, David Holden, Joanne Bailey, Reagan Dwyer, Johanna Milner, John Moshfegh, Alanna TI Development of a flavonoid database for assessing population exposures and its application SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology Meeting CY APR 21-25, 2012 CL San Diego, CA C1 [Ahuja, Jaspreet K. C.; Bhagwat, Seema; Haytowitz, David; Holden, Joanne; Moshfegh, Alanna] ARS, USDA, Beltsville Human Nutr Res Ctr, Beltsville, MD USA. [Bailey, Reagan; Dwyer, Johanna] NIH, Off Dietary Supplements, Bethesda, MD 20892 USA. [Milner, John] NCI, NIH, Rockville, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 5 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR PY 2012 VL 26 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 032IZ UT WOS:000310711304421 ER PT J AU Akinfiresoye, L Lovinger, DM Tizabi, Y AF Akinfiresoye, Luli Lovinger, D. M. Tizabi, Y. TI Antidepressant-like effect of AMPA and ketamine combination in male Wistar -Kyoto rats SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology Meeting CY APR 21-25, 2012 CL San Diego, CA C1 [Akinfiresoye, Luli; Tizabi, Y.] Howard Univ, Coll Med, Dept Pharmacol, Washington, DC 20059 USA. [Lovinger, D. M.] NIAAA, Lab Integrat Neurosci, Div Intramural Clin & Basic Res, NIH, Rockville, MD 20852 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR PY 2012 VL 26 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 032IZ UT WOS:000310711307213 ER PT J AU Andrews, KW Roseland, JM Holden, JM Middleton, AM Solomon, AM Douglass, L Dwyer, JT Bailey, R Saldanha, LG Daniel, MG AF Andrews, K. W. Roseland, J. M. Holden, J. M. Middleton, A. M. Solomon, A. M. Douglass, L. Dwyer, J. T. Bailey, R. Saldanha, L. G. Daniel, M. G. TI Release 2 of the US Dietary Supplement Ingredient Database (DSID): research protocols and ingredient estimates for children's and adult multivitamins SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology Meeting CY APR 21-25, 2012 CL San Diego, CA C1 [Andrews, K. W.; Roseland, J. M.; Holden, J. M.; Middleton, A. M.; Solomon, A. M.; Daniel, M. G.] USDA, Nutrient Data Lab, Beltsville, MD 20705 USA. [Dwyer, J. T.; Bailey, R.; Saldanha, L. G.] NIH, Off Dietary Supplements, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR PY 2012 VL 26 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 032IZ UT WOS:000310711303114 ER PT J AU Arab, L Su, J Steck, S Ang, A Fontham, E Bensen, J Mohler, J AF Arab, Lenore Su, Joseph Steck, Susan Ang, Alfonso Fontham, Elizabeth Bensen, Jeannette Mohler, James TI Living WCRF Recommendations associated with less Prostate Cancer Aggressiveness among African and Caucasian Americans SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology Meeting CY APR 21-25, 2012 CL San Diego, CA C1 [Arab, Lenore; Ang, Alfonso] Univ Calif Los Angeles, Dept Med, Los Angeles, CA 90024 USA. [Su, Joseph] NCI, Bethseda, MD USA. [Steck, Susan] USC, Columbus, SC USA. [Fontham, Elizabeth] LSU, New Orleans, LA USA. [Mohler, James] UNC, Sch Med, Chapel Hill, NC USA. [Mohler, James] Roswell Pk Canc Inst, Buffalo, NY 14263 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR PY 2012 VL 26 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 032IZ UT WOS:000310711306903 ER PT J AU Artis, M Huestis, D Lehmann, T AF Artis, Monica Huestis, Diana Lehmann, Tovi TI Variation in cuticular hydrocarbons with age, feeding, and insemination status of Anopheles gambiae SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology Meeting CY APR 21-25, 2012 CL San Diego, CA C1 [Artis, Monica] Univ Maryland Eastern Shore, Princess Anne, MD USA. [Huestis, Diana; Lehmann, Tovi] NIAID, NIH, Rockville, MD USA. NR 0 TC 0 Z9 0 U1 1 U2 2 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR PY 2012 VL 26 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 032IZ UT WOS:000310711301054 ER PT J AU Barry, CE AF Barry, Clifton Earl TI Compensatory Evolution and Fixation of Rfampicin Resistance in MDR and XDR Tuberculosis. SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology Meeting CY APR 21-25, 2012 CL San Diego, CA C1 [Barry, Clifton Earl] NIAID, TB Res Sect 3, NIH, Bethesda, MD 20892 USA. RI Barry, III, Clifton/H-3839-2012 NR 0 TC 0 Z9 0 U1 0 U2 1 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR PY 2012 VL 26 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 032IZ UT WOS:000310711301980 ER PT J AU Benischke, AS Hemion, C Neutzner, M Norris, K Frank, S Youle, R Karbowski, M Neutzner, A AF Benischke, Anne-Sophie Hemion, Charles Neutzner, Melanie Norris, Kristi Frank, Stefan Youle, Richard Karbowski, Mariusz Neutzner, Albert TI A novel mitochondrial ubiquitin ligase involved in the regulation of mitochondrial fusion SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology Meeting CY APR 21-25, 2012 CL San Diego, CA C1 [Benischke, Anne-Sophie; Hemion, Charles; Neutzner, Melanie; Neutzner, Albert] Dept Biomed, Basel, Switzerland. [Norris, Kristi; Youle, Richard] NIH, Bethesda, MD 20892 USA. [Frank, Stefan] Univ Basel, Inst Pathol, Basel, Switzerland. [Karbowski, Mariusz] Univ Maryland, Inst Biotechnol, Baltimore, MD 21201 USA. NR 0 TC 0 Z9 0 U1 0 U2 2 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR PY 2012 VL 26 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 032IZ UT WOS:000310711304218 ER PT J AU Bortner, CD Scoltock, AB Sifre, MI Cidlowski, JA AF Bortner, Carl David Scoltock, Alyson B. Sifre, Maria I. Cidlowski, John A. TI Osmotic Stress Resistance Imparts Acquired Anti-Apoptotic Properties in Lymphocytes via Regulatory Cell Volume Mechanisms SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology Meeting CY APR 21-25, 2012 CL San Diego, CA C1 [Bortner, Carl David; Scoltock, Alyson B.; Sifre, Maria I.; Cidlowski, John A.] NIEHS, Lab Signal Transduct, NIH, Res Triangle Pk, NC 27709 USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR PY 2012 VL 26 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 032IZ UT WOS:000310711303102 ER PT J AU Branum, A Singer, B Bailey, R AF Branum, Amy Singer, Barbara Bailey, Regan TI Dietary supplement use during pregnancy: results from the National Health and Nutritional Examination Survey (NHANES) SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology Meeting CY APR 21-25, 2012 CL San Diego, CA C1 [Branum, Amy] CDC NCHS, Hyattsville, MD USA. [Singer, Barbara] Univ Maryland, College Pk, MD 20742 USA. [Bailey, Regan] NIH, Off Dietary Supplements, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 3 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR PY 2012 VL 26 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 032IZ UT WOS:000310711301614 ER PT J AU Brosh, RM Sommers, J Muniandy, P Coulombe, Y Masson, JY Seidman, M Suhasini, A AF Brosh, Robert Michael Sommers, Joshua Muniandy, Parameswary Coulombe, Yan Masson, Jean-Yves Seidman, Michael Suhasini, Avvaru TI Physical and Functional Interaction Between Fanconi Anemia Group J Helicase and MRE11 Nuclease SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology Meeting CY APR 21-25, 2012 CL San Diego, CA C1 [Brosh, Robert Michael; Sommers, Joshua; Muniandy, Parameswary; Seidman, Michael; Suhasini, Avvaru] NIA, Lab Mol Gerontol, NIH, Baltimore, MD 21224 USA. [Coulombe, Yan; Masson, Jean-Yves] Univ Laval, Canc Res Ctr, Genome Stabil Lab, Quebec City, PQ, Canada. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR PY 2012 VL 26 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 032IZ UT WOS:000310711303009 ER PT J AU Buchowski, M Whitaker, L Powers, J Chen, K Schnelle, J AF Buchowski, Maciej Whitaker, Lauren Powers, James Chen, Kong Schnelle, John TI Fatigability as a function of physical activity energy expenditure: proof of concept SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology Meeting CY APR 21-25, 2012 CL San Diego, CA C1 [Buchowski, Maciej; Whitaker, Lauren; Powers, James; Schnelle, John] Vanderbilt Univ, Nashville, TN USA. [Chen, Kong] NIDDK, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR PY 2012 VL 26 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 032IZ UT WOS:000310711304338 ER PT J AU Byun, JS Gardner, K AF Byun, Jung S. Gardner, Kevin TI The ELL component of the SEC complex facilitates RNA polymerase II pause site entry and release SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology Meeting CY APR 21-25, 2012 CL San Diego, CA C1 [Byun, Jung S.; Gardner, Kevin] NCI, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR PY 2012 VL 26 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 032IZ UT WOS:000310711301709 ER PT J AU Byun, JS Gardner, K AF Byun, Jung S. Gardner, Kevin TI Reprogramming the cancer epigenome by "metabolic transduction" SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology Meeting CY APR 21-25, 2012 CL San Diego, CA C1 [Byun, Jung S.; Gardner, Kevin] NCI, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR PY 2012 VL 26 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 032IZ UT WOS:000310711301596 ER PT J AU Carlson, B Kim, JY Xu, XM Yoo, MH Zeng, Y Chen, S Gladyshev, V Lee, BJ Hatfield, D AF Carlson, Bradley Kim, Jin Young Xu, Xue-Ming Yoo, Min Hyuk Zeng, Yu Chen, Shawn Gladyshev, Vadim Lee, Byeong Jae Hatfield, Dolph TI Inhibition of selenocysteine tRNA[Ser]Sec aminoacylation provides evidence that aminoacylation is required for regulatory methylation of this tRNA SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology Meeting CY APR 21-25, 2012 CL San Diego, CA C1 [Carlson, Bradley; Xu, Xue-Ming; Yoo, Min Hyuk; Hatfield, Dolph] NCI, NIH, Bethesda, MD 20892 USA. [Kim, Jin Young; Lee, Byeong Jae] Seoul Natl Univ, Seoul, South Korea. [Zeng, Yu; Chen, Shawn] Ohio Univ, Athens, OH 45701 USA. [Gladyshev, Vadim] Brigham & Womens Hosp, Boston, MA 02115 USA. [Gladyshev, Vadim] Harvard Univ, Sch Med, Boston, MA USA. RI Gladyshev, Vadim/A-9894-2013 NR 0 TC 0 Z9 0 U1 0 U2 1 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR PY 2012 VL 26 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 032IZ UT WOS:000310711302548 ER PT J AU Chandra, G Saha, A Moralle, MR Zhang, ZJ Sarkar, C Peng, SY Mukherjee, AB AF Chandra, Goutam Saha, Arjun Moralle, Matthew R. Zhang, Zhongjian Sarkar, Chinmoy Peng, Shiyong Mukherjee, Anil B. TI Impaired lysosomal maturation of pro-cathepsin D to active cathepsin D in a childhood neurodegenerative lysosomal storage disease SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology Meeting CY APR 21-25, 2012 CL San Diego, CA C1 [Chandra, Goutam; Saha, Arjun; Moralle, Matthew R.; Zhang, Zhongjian; Sarkar, Chinmoy; Peng, Shiyong; Mukherjee, Anil B.] NICHD, Sect Dev Genet, NIH, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR PY 2012 VL 26 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 032IZ UT WOS:000310711303433 ER PT J AU Charron, CS Clevidence, BA Albaugh, GP Kramer, M Vinyard, BT Milner, JA Novotny, JA AF Charron, Craig S. Clevidence, Beverly A. Albaugh, George P. Kramer, Matthew Vinyard, Bryan T. Milner, John A. Novotny, Janet A. TI Influence of consumption of allyl isothiocyanate or cabbage and mustard on DNA integrity in humans SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology Meeting CY APR 21-25, 2012 CL San Diego, CA C1 [Charron, Craig S.; Clevidence, Beverly A.; Albaugh, George P.; Novotny, Janet A.] USDA, Beltsville Human Nutr Res Ctr, Beltsville, MD 20705 USA. [Kramer, Matthew; Vinyard, Bryan T.] USDA, Biometr Consulting Serv, Beltsville, MD 20705 USA. [Milner, John A.] NCI, Div Canc Prevent, Rockville, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 2 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR PY 2012 VL 26 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 032IZ UT WOS:000310711305025 ER PT J AU Chavis, JT Neal, J Switzer, C Wink, DA Garcin, E AF Chavis, John Taylor, III Neal, Jacob Switzer, Christopher Wink, David A., Jr. Garcin, Elsa TI Determining the effect of dithiolethione compounds on the activity of human glyceraldehyde-3-phosphate dehydrogenase SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology Meeting CY APR 21-25, 2012 CL San Diego, CA C1 [Chavis, John Taylor, III; Neal, Jacob; Garcin, Elsa] Univ Maryland Baltimore Cty, Baltimore, MD 21228 USA. [Switzer, Christopher; Wink, David A., Jr.] NCI, Radiat Biol Branch, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 1 U2 4 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR PY 2012 VL 26 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 032IZ UT WOS:000310711301068 ER PT J AU Chen, F Hofmann, P Carlson, BA Tobe, R Schomburg, L Gladyshev, VN Schweizer, U Hatfield, DL AF Chen, Fang Hofmann, Peter Carlson, Bradley A. Tobe, Ryuta Schomburg, Lutz Gladyshev, Vadim N. Schweizer, Ulrich Hatfield, Dolph L. TI Mammalian selenocysteine tRNA Um34 methylase and its role in selenoprotein synthesis SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology Meeting CY APR 21-25, 2012 CL San Diego, CA C1 [Chen, Fang; Carlson, Bradley A.; Tobe, Ryuta; Hatfield, Dolph L.] NCI, NIH, Bethesda, MD 20892 USA. [Hofmann, Peter; Schomburg, Lutz; Schweizer, Ulrich] Charite, D-13353 Berlin, Germany. [Gladyshev, Vadim N.] Harvard Univ, Sch Med, Boston, MD USA. [Gladyshev, Vadim N.] Brigham & Womens Hosp, Boston, MD USA. RI Gladyshev, Vadim/A-9894-2013; Schomburg, Lutz/D-8096-2013; Schweizer, Ulrich/E-8105-2013 NR 0 TC 0 Z9 0 U1 0 U2 2 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR PY 2012 VL 26 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 032IZ UT WOS:000310711303301 ER PT J AU Chen, L Murray-Kolb, LE Patel, KV AF Chen, Lenis Murray-Kolb, Laura E. Patel, Kushang V. TI The Characterization of Iron Status in InCHIANTI: The Use of a Higher Ferritin Cutoff SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology Meeting CY APR 21-25, 2012 CL San Diego, CA C1 [Chen, Lenis; Murray-Kolb, Laura E.] Johns Hopkins Bloomberg Sch Publ Hlth, Baltimore, MD USA. [Murray-Kolb, Laura E.] Penn State Univ, Dept Nutr Sci, University Pk, PA 16802 USA. [Patel, Kushang V.] NIA, Lab Epidemiol Demog & Biometry, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR PY 2012 VL 26 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 032IZ UT WOS:000310711302275 ER PT J AU Chou, CL Han, L Wang, G Gucek, M Pisitkun, T Knepper, MA AF Chou, C. L. Han, L. Wang, G. Gucek, M. Pisitkun, T. Knepper, M. A. TI Stoichiometry determination of UT-A1 and UT-A3 within collecting duct urea transporter complex SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology Meeting CY APR 21-25, 2012 CL San Diego, CA C1 [Chou, C. L.; Han, L.; Wang, G.; Gucek, M.; Pisitkun, T.; Knepper, M. A.] NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 2 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR PY 2012 VL 26 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 032IZ UT WOS:000310711305151 ER PT J AU Coates, PM Bailey, RL AF Coates, Paul M. Bailey, Regan L. TI Making sense of dietary supplement research and a framework for the future SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology Meeting CY APR 21-25, 2012 CL San Diego, CA C1 [Coates, Paul M.; Bailey, Regan L.] NIH, Off Dietary Supplements, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR PY 2012 VL 26 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 032IZ UT WOS:000310711301077 ER PT J AU Conroy, J Free, RB Doyle, TB Southall, N Ferrer, M Han, Y Javitch, JA Sibley, DR AF Conroy, Jennie Free, R. Benjamin Doyle, Trevor B. Southall, Noel Ferrer, Marc Han, Yang Javitch, Jonathan A. Sibley, David R. TI Identification of a novel dopaminergic agonist that selectively activates the D-2 dopamine receptor SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology Meeting CY APR 21-25, 2012 CL San Diego, CA C1 [Conroy, Jennie; Free, R. Benjamin; Doyle, Trevor B.; Sibley, David R.] NINDS, MNS, NIH, Rockville, MD USA. [Southall, Noel; Ferrer, Marc] NIH, Ctr Translat Therapeut, Bethesda, MD 20892 USA. [Han, Yang; Javitch, Jonathan A.] Columbia Univ Coll Phys & Surg, Ctr Mol Recognit, New York, NY 10032 USA. NR 0 TC 0 Z9 0 U1 0 U2 2 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR PY 2012 VL 26 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 032IZ UT WOS:000310711304809 ER PT J AU Costello, RB Lentino, C Saldanha, L Srinivas, P Sempos, C AF Costello, Rebecca B. Lentino, Cindy Saldanha, Leila Srinivas, Pothur Sempos, Chris TI Review of select dietary supplement interventions for endothelial dysfunction SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology Meeting CY APR 21-25, 2012 CL San Diego, CA C1 [Costello, Rebecca B.; Lentino, Cindy; Saldanha, Leila; Sempos, Chris] Off Dietary Supplements, Bethesda, MD USA. [Srinivas, Pothur] NHLBI, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR PY 2012 VL 26 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 032IZ UT WOS:000310711304759 ER PT J AU Cox, B Post, J Bull, G Gouty, S Woods, A AF Cox, Brian Post, Jeremy Bull, Gregory Gouty, Shawn Woods, Amina TI Mass-spectrometric analysis of changes in brain lipid expression and distribution after brain injury SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology Meeting CY APR 21-25, 2012 CL San Diego, CA C1 [Cox, Brian; Bull, Gregory; Gouty, Shawn] Uniformed Serv Univ Hlth Sci, Bethesda, MD 20814 USA. [Cox, Brian; Post, Jeremy; Bull, Gregory; Woods, Amina] NIH, USU, CNRM, Bethesda, MD USA. [Post, Jeremy; Woods, Amina] NIDA, Struct Biol Unit, IRP, Baltimore, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 3 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR PY 2012 VL 26 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 032IZ UT WOS:000310711304866 ER PT J AU Dai, LS Tsai-Morris, CH Sato, H Villar, J Zhang, JB Dufau, ML AF Dai, L-S Tsai-Morris, C. H. Sato, H. Villar, J. Zhang, J-B Dufau, M. L. TI Regulation of exclusively testis-expressed microRNA-469 by Gonadotropin-Regulated Testicular RNA Helicase controls male germ cells development SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology Meeting CY APR 21-25, 2012 CL San Diego, CA C1 [Dai, L-S; Tsai-Morris, C. H.; Sato, H.; Villar, J.; Dufau, M. L.] NICHD, Sect Mol Endocrinol, PDEGEN, NIH, Bethesda, MD USA. [Dai, L-S; Zhang, J-B] Jilin Univ, Coll Anim Sci & Vet Med, Lab Anim Ctr, Jilin, Jilin, Peoples R China. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR PY 2012 VL 26 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 032IZ UT WOS:000310711300444 ER PT J AU Dodd, KW Verkaik-Kloosterman, J Dekkers, A vantVeer, P Ocke, M AF Dodd, Kevin Wayne Verkaik-Kloosterman, Janneke Dekkers, Arnold vantVeer, Pieter Ocke, Marga TI A three-part mixed-effects model to estimate usual total nutrient distributions from food and dietary supplements SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology Meeting CY APR 21-25, 2012 CL San Diego, CA C1 [Dodd, Kevin Wayne] NCI, Biometry Res Grp, Canc Prevent Div, Bethesda, MD 20892 USA. [Verkaik-Kloosterman, Janneke; Dekkers, Arnold; Ocke, Marga] Natl Inst Publ Hlth & Environm RIVM, Ctr Nutr & Hlth CVG, Bilthoven, Netherlands. [vantVeer, Pieter] Wageningen Univ, Div Human Nutr, Wageningen, Netherlands. NR 0 TC 0 Z9 0 U1 0 U2 1 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR PY 2012 VL 26 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 032IZ UT WOS:000310711305735 ER PT J AU Du, LL Gao, ZG van Veldhoven, JPD IJzerman, AP Jacobson, KA Auchampach, JA AF Du, Lili Gao, Zhan-Guo van Veldhoven, Jacobus P. D. IJzerman, Adriaan P. Jacobson, Kenneth A. Auchampach, John A. TI Activity of LUF6000 and LUF6096 as positive allosteric modulators (PAMs) for the A3 adenosine receptor (AR) is species-dependent SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology Meeting CY APR 21-25, 2012 CL San Diego, CA C1 [Du, Lili; Auchampach, John A.] Med Coll Wisconsin, Dept Pharmacol & Toxicol, Milwaukee, WI 53226 USA. [Gao, Zhan-Guo; Jacobson, Kenneth A.] NIDDKD, NIH, Bethesda, MD 20892 USA. [van Veldhoven, Jacobus P. D.; IJzerman, Adriaan P.] Leiden Univ, LACDR, Div Med Chem, Leiden, Netherlands. RI Jacobson, Kenneth/A-1530-2009 OI Jacobson, Kenneth/0000-0001-8104-1493 NR 0 TC 0 Z9 0 U1 0 U2 3 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR PY 2012 VL 26 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 032IZ UT WOS:000310711303182 ER PT J AU Duchez, B Milgram, S Playford, MP AF Duchez, Brian Milgram, Sharon Playford, Martin Peter TI Characterization of the interaction between Sorting Nexin 27 and beta-Catenin in kidney epithelial cells SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology Meeting CY APR 21-25, 2012 CL San Diego, CA C1 [Duchez, Brian; Milgram, Sharon; Playford, Martin Peter] NHLBI, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR PY 2012 VL 26 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 032IZ UT WOS:000310711306343 ER PT J AU Duncan, T Samuel, W Kutty, RK Redmond, TM AF Duncan, Todd Samuel, William Kutty, R. Krishnan Redmond, T. Michael TI Alteration of sphingolipid metabolism during 4-HPR induced cell death in the ARPE-19 human retinal pigment epithelial cell line SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology Meeting CY APR 21-25, 2012 CL San Diego, CA C1 [Duncan, Todd; Samuel, William; Kutty, R. Krishnan; Redmond, T. Michael] NEI, Lab Retinal Cell & Mol Biol, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR PY 2012 VL 26 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 032IZ UT WOS:000310711300958 ER PT J AU Dwyer, JT Bailey, R Nahin, R Rogers, G Sempos, C Jacques, P AF Dwyer, Johanna T. Bailey, Regan Nahin, Richard Rogers, Gail Sempos, Christopher Jacques, Paul TI Dietary supplement (DS) use of children < 18 yr in the 2007 National Health Interview Survey (NHIS) SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology Meeting CY APR 21-25, 2012 CL San Diego, CA C1 [Dwyer, Johanna T.; Bailey, Regan; Sempos, Christopher] NIH, Off Dietary Supplements, Bethesda, MD 20892 USA. [Nahin, Richard] NCCAM, NIH, Bethesda, MD USA. [Rogers, Gail; Jacques, Paul] Tufts Univ, USDA, Human Nutr Res Ctr Aging, Boston, MA 02111 USA. NR 0 TC 0 Z9 0 U1 0 U2 4 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR PY 2012 VL 26 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 032IZ UT WOS:000310711301271 ER PT J AU Dwyer, JT Bailey, R Saldanha, L Holden, J Andrews, K Betz, J Gahche, J Hardy, C Milner, J Roseland, J AF Dwyer, Johanna T. Bailey, Regan Saldanha, Leila Holden, Joanne Andrews, Karen Betz, Joseph Gahche, Jaime Hardy, Constance Milner, John Roseland, Janet TI Progress in development of dietary supplement (DS) composition and label databases for research SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology Meeting CY APR 21-25, 2012 CL San Diego, CA C1 [Dwyer, Johanna T.; Bailey, Regan; Saldanha, Leila; Betz, Joseph] Off Dietary Supplements, Bethesda, MD USA. [Milner, John] NCI, NIH, Bethesda, MD 20892 USA. [Holden, Joanne; Andrews, Karen; Roseland, Janet] USDA, Nutrient Data Lab, Beltsville, MD 20705 USA. [Gahche, Jaime] CDC, NCHS, Hysattsville, MD USA. [Hardy, Constance] US FDA, CFSAN, Silver Spring, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 3 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR PY 2012 VL 26 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 032IZ UT WOS:000310711301264 ER PT J AU Fantegrossi, WE Zimmerman, SM Rice, KC AF Fantegrossi, William E. Zimmerman, Sarah M. Rice, Kenner C. TI In vivo effects of "bath salt" constituent 3,4-methylenedioxypyrovalerone (MDPV) in mice: contribution of ambient temperature and monoamines SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology Meeting CY APR 21-25, 2012 CL San Diego, CA C1 [Fantegrossi, William E.; Zimmerman, Sarah M.] Univ Arkansas Med Sci, Little Rock, AR 72205 USA. [Rice, Kenner C.] NIDA, Drug Design & Synth Sect, CBRB, NIH, Rockville, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR PY 2012 VL 26 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 032IZ UT WOS:000310711302560 ER PT J AU Free, RB Dalefield, M Miller, BN Doyle, TB Conroy, JL Vangveravong, S Duan, LH Javitch, JA Mach, RH Sibley, DR AF Free, R. Benjamin Dalefield, Martin Miller, Brittney N. Doyle, Trevor B. Conroy, Jennie L. Vangveravong, Suwanna Duan, Lihua Javitch, Jonathan A. Mach, Robert H. Sibley, David R. TI The antipsychotic aripiprazole is a non-competitive antagonist of dopamine-stimulated D-2 receptor interactions with beta-arrestin-2 SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology Meeting CY APR 21-25, 2012 CL San Diego, CA C1 [Free, R. Benjamin; Dalefield, Martin; Miller, Brittney N.; Doyle, Trevor B.; Conroy, Jennie L.; Sibley, David R.] NINDS, MNS, Rockville, MD USA. [Vangveravong, Suwanna; Mach, Robert H.] Washington Univ, Sch Med, St Louis, MO USA. [Duan, Lihua; Javitch, Jonathan A.] Columbia Univ Coll Phys & Surg, Ctr Mol Recognit, New York, NY 10032 USA. NR 0 TC 0 Z9 0 U1 0 U2 4 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR PY 2012 VL 26 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 032IZ UT WOS:000310711304496 ER PT J AU Freeman, LB AF Freeman, Laura Beane TI Occupational formaldehyde exposure and cancer risk SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology Meeting CY APR 21-25, 2012 CL San Diego, CA C1 [Freeman, Laura Beane] NCI, Occupat & Environm Epidemiol Branch, Bethesda, MD 20892 USA. RI Beane Freeman, Laura/C-4468-2015 OI Beane Freeman, Laura/0000-0003-1294-4124 NR 0 TC 0 Z9 0 U1 0 U2 5 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR PY 2012 VL 26 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 032IZ UT WOS:000310711300260 ER PT J AU Gericke, A Ross, AH King, KE Neuman, BM Jiang, ZP AF Gericke, Arne Ross, Alonzo H. King, Katrice E. Neuman, Brittany M. Jiang, Zhiping TI PTEN binding properties for different model membrane morphologies SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology Meeting CY APR 21-25, 2012 CL San Diego, CA C1 [Gericke, Arne; King, Katrice E.; Neuman, Brittany M.] Worcester Polytech Inst, Worcester, MA 01609 USA. [Ross, Alonzo H.] Univ Massachusetts, Sch Med, Worcester, MA USA. [Jiang, Zhiping] NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR PY 2012 VL 26 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 032IZ UT WOS:000310711306663 ER PT J AU Glancy, B Hsu, LY Dao, L Bakalar, M French, S Chess, DJ Taylor, JL Daniels, MP Esfahani, S Balaban, RS AF Glancy, Brian Hsu, Li-Yueh Dao, Lam Bakalar, Matthew French, Stephanie Chess, David J. Taylor, Joni L. Daniels, Mathew P. Esfahani, Shervin Balaban, Robert S. TI Capillaries are Embedded in the Sarcolemma of Murine Slow Twitch Skeletal Muscle Fibers SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology Meeting CY APR 21-25, 2012 CL San Diego, CA C1 [Glancy, Brian; Hsu, Li-Yueh; Dao, Lam; Bakalar, Matthew; French, Stephanie; Chess, David J.; Taylor, Joni L.; Daniels, Mathew P.; Esfahani, Shervin; Balaban, Robert S.] NHLBI, NIH, Bethesda, MD 20892 USA. RI Glancy, Brian/P-3163-2016 OI Glancy, Brian/0000-0002-8571-244X NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR PY 2012 VL 26 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 032IZ UT WOS:000310711304871 ER PT J AU Goldstein, DS AF Goldstein, David S. TI Clinical Methods to Assess Cardiac Sympathetic Innervation and Function SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology Meeting CY APR 21-25, 2012 CL San Diego, CA C1 [Goldstein, David S.] NINDS, Clin Neurocardiol Sect, CNP, DIR,NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR PY 2012 VL 26 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 032IZ UT WOS:000310711300122 ER PT J AU Green, ML Manjerovic, MB Mateus-Pinilla, NE Kelly, AC Shelton, P Novakofski, J AF Green, Michelle L. Manjerovic, Mary Beth Mateus-Pinilla, Nohra E. Kelly, Amy C. Shelton, Paul Novakofski, Jan TI Determining source populations of newly identified cases of chronic wasting disease in white-tailed deer SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology Meeting CY APR 21-25, 2012 CL San Diego, CA C1 [Green, Michelle L.; Manjerovic, Mary Beth; Kelly, Amy C.; Novakofski, Jan] Univ Illinois, Urbana, IL 61801 USA. [Green, Michelle L.; Manjerovic, Mary Beth; Mateus-Pinilla, Nohra E.] Univ Illinois, Illinois Nat Hist Survey, Champaign, IL 61820 USA. [Kelly, Amy C.] NIDDK, NIH, Bethesda, MD USA. [Shelton, Paul] Illinois Dept Nat Resources, Div Wildlife Resources, Springfield, IL USA. NR 0 TC 0 Z9 0 U1 0 U2 9 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR PY 2012 VL 26 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 032IZ UT WOS:000310711305775 ER PT J AU Groene, HJ Wang, SJ Papatriantafyllou, M Kaya, Z Burgdorf, S Young, MF Schaefer, L Popovic, ZV AF Groene, Hermann-Josef Wang, Shijun Papatriantafyllou, Maria Kaya, Ziya Burgdorf, Sven Young, Marian F. Schaefer, Liliana Popovic, Zoran V. TI The proteoglycan biglycan enhances antigen-specific T cell activation potentially via MyD88 and TRIF pathways and triggers autoimmune perimyocarditis SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology Meeting CY APR 21-25, 2012 CL San Diego, CA C1 [Groene, Hermann-Josef; Wang, Shijun; Papatriantafyllou, Maria; Popovic, Zoran V.] German Canc Res Ctr, D-6900 Heidelberg, Germany. [Kaya, Ziya] Univ Heidelberg, Univ Heidelberg Hosp, Heidelberg, Germany. [Burgdorf, Sven] Univ Hosp Bonn, Inst Mol Med, Bonn, Germany. [Burgdorf, Sven] Univ Hosp Bonn, Inst Expt Immunol, Bonn, Germany. [Young, Marian F.] Natl Inst Dent & Craniofacial Res, Craniofacial & Skeletal Dis Branch, Bethesda, MD USA. [Schaefer, Liliana] Goethe Univ Clin, Frankfurt, Germany. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR PY 2012 VL 26 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 032IZ UT WOS:000310711305878 ER PT J AU Guenther, PM O'Connell, KM Reedy, J Kirkpatrick, SI Hiza, HAB Kuczynski, KJ AF Guenther, Patricia M. O'Connell, Kellie M. Reedy, Jill Kirkpatrick, Sharon I. Hiza, Hazel A. B. Kuczynski, Kevin J. TI Development of the Healthy Eating Index-2010 SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology Meeting CY APR 21-25, 2012 CL San Diego, CA C1 [Guenther, Patricia M.; O'Connell, Kellie M.; Hiza, Hazel A. B.; Kuczynski, Kevin J.] USDA, Ctr Nutr Policy & Promot, Alexandria, VA USA. [Reedy, Jill; Kirkpatrick, Sharon I.] NCI, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 1 U2 7 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR PY 2012 VL 26 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 032IZ UT WOS:000310711301470 ER PT J AU Hager, GL AF Hager, Gordon L. TI Molecular dynamics of epigenetic transitions SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology Meeting CY APR 21-25, 2012 CL San Diego, CA C1 [Hager, Gordon L.] NCI, Lab Receptor Biol & Gene Express, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR PY 2012 VL 26 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 032IZ UT WOS:000310711304569 ER PT J AU Hanover, JA Wang, P Ghosh, S Keembiyehetty, C Comly, M Bond, M Krause, M Love, D AF Hanover, John A. Wang, Peng Ghosh, Salil Keembiyehetty, Chithra Comly, Marcy Bond, Michelle Krause, Michael Love, Dona TI O-GlcNAc cycling and Epigenetics SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology Meeting CY APR 21-25, 2012 CL San Diego, CA C1 [Hanover, John A.; Wang, Peng; Ghosh, Salil; Keembiyehetty, Chithra; Comly, Marcy; Bond, Michelle; Love, Dona] NIDDK, LCMB, Bethesda, MD USA. [Krause, Michael] NIDDK, LMB, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 1 U2 3 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR PY 2012 VL 26 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 032IZ UT WOS:000310711303247 ER PT J AU Hiranita, T Li, LB Hayashi, S Cao, JJ AF Hiranita, Takato Li, Libin Hayashi, Shuichiro Cao, Jianjing TI Can the Stereotypy-Inducing Effects of Atypical Dopamine Uptake Inhibitors Account for Their Blockade of Cocaine Self Administration? SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology Meeting CY APR 21-25, 2012 CL San Diego, CA C1 [Hiranita, Takato; Li, Libin; Hayashi, Shuichiro; Cao, Jianjing] NIDA IRP NIH DHHS, Mol Targets & Medicat Discovery Branch, Baltimore, MD USA. RI Hiranita, Takato/G-6567-2011 NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR PY 2012 VL 26 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 032IZ UT WOS:000310711304497 ER PT J AU Hueschen, CL Zimmerman, SP Milgram, SL Playford, MP AF Hueschen, Christina Lynn Zimmerman, Seth Paul Milgram, Sharon Lynn Playford, Martin Peter TI Sorting Nexin 27 mediates PDZ-directed trafficking of Zona-Occludens (ZO)-2 to the Tight Junction SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology Meeting CY APR 21-25, 2012 CL San Diego, CA C1 [Hueschen, Christina Lynn; Zimmerman, Seth Paul; Milgram, Sharon Lynn; Playford, Martin Peter] NHLBI, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR PY 2012 VL 26 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 032IZ UT WOS:000310711306142 ER PT J AU Izumi, Y Burg, MB Ferraris, JD AF Izumi, Yuichiro Burg, Maurice B. Ferraris, Joan D. TI Regulated intramembrane proteolysis contributes to control of the osmoprotective transcription factor, NFAT5. SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology Meeting CY APR 21-25, 2012 CL San Diego, CA C1 [Izumi, Yuichiro; Burg, Maurice B.; Ferraris, Joan D.] NHLBI, SBC, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR PY 2012 VL 26 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 032IZ UT WOS:000310711301780 ER PT J AU Jensen, TB Pisitkun, T Hoffert, JD Fenton, RA Praetorius, HA Jensen, UB Knepper, MA Praetorius, J AF Jensen, Thomas Buus Pisitkun, Trairak Hoffert, Jason D. Fenton, Robert A. Praetorius, Helle A. Jensen, Uffe Birk Knepper, Mark A. Praetorius, Jeppe TI Identification of proteins regulated by 24-hour aldosterone treatment in late distal convoluted tubules, connecting tubules and initial cortical collecting ducts SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology Meeting CY APR 21-25, 2012 CL San Diego, CA C1 [Jensen, Thomas Buus; Fenton, Robert A.; Praetorius, Helle A.; Jensen, Uffe Birk; Praetorius, Jeppe] Aarhus Univ, Dept Biomed, Aarhus, Denmark. [Pisitkun, Trairak; Hoffert, Jason D.; Knepper, Mark A.] NHLBI, Epithelial Syst Biol Lab, NIH, Bethesda, MD 20892 USA. [Jensen, Uffe Birk] Aarhus Univ Hosp, Dept Clin Med Clin Genet, DK-8000 Aarhus, Denmark. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR PY 2012 VL 26 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 032IZ UT WOS:000310711300729 ER PT J AU Johnson, JM Tominaga, K Gorospe, M Abdelmohsen, K AF Johnson, Jessica Michelle Tominaga, Kumiko Gorospe, Myriam Abdelmohsen, Kotb TI Regulation of microRNA Expression by AUF1 Through Dicer SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology Meeting CY APR 21-25, 2012 CL San Diego, CA C1 [Johnson, Jessica Michelle] Unvers Maryland Eastern Shore, Dept Nat Sci, Princess Anne, MD USA. [Tominaga, Kumiko; Gorospe, Myriam; Abdelmohsen, Kotb] NIA, NIH, Baltimore, MD 21224 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR PY 2012 VL 26 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 032IZ UT WOS:000310711301456 ER PT J AU Jovic, M Bojjireddy, N Kean, M Gingras, AC Brill, J Balla, T AF Jovic, Marko Bojjireddy, Naveen Kean, Michelle Gingras, Anne-Claude Brill, Julie Balla, Tamas TI Regulation of PI4KII alpha distribution between the Golgi and endosomal compartments SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology Meeting CY APR 21-25, 2012 CL San Diego, CA C1 [Jovic, Marko; Bojjireddy, Naveen; Balla, Tamas] NICHD, NIH, Bethesda, MD USA. [Kean, Michelle; Gingras, Anne-Claude] Mt Sinai Hosp, Samuel Lunenfeld Res Inst, Toronto, ON M5G 1X5, Canada. [Brill, Julie] Hosp Sick Children, Cell Biol Program, Toronto, ON M5G 1X8, Canada. NR 0 TC 0 Z9 0 U1 0 U2 1 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR PY 2012 VL 26 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 032IZ UT WOS:000310711306265 ER PT J AU Kang, GS Cates, K Pacheco-Rodriguez, G Meza-Carmen, V Daniels, M Connelly, P Moss, J Vaughan, M AF Kang, Gi Soo Cates, Krystal Pacheco-Rodriguez, Gustavo Meza-Carmen, Victor Daniels, Mathew Connelly, Patricia Moss, Joel Vaughan, Martha TI Role of ADP-ribosylation factor domain protein 1 (ARD1/TRIM23) on lysosome biogenesis and function SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology Meeting CY APR 21-25, 2012 CL San Diego, CA C1 [Kang, Gi Soo; Cates, Krystal; Pacheco-Rodriguez, Gustavo; Meza-Carmen, Victor; Daniels, Mathew; Connelly, Patricia; Moss, Joel; Vaughan, Martha] NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 1 U2 3 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR PY 2012 VL 26 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 032IZ UT WOS:000310711302936 ER PT J AU Kant, AK Graubard, BI AF Kant, Ashima K. Graubard, Barry I. TI Race/ethnicity, family income, and education differentials in nutritional biomarkers in American children and adolescents: NHANES 2003-2006 SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology Meeting CY APR 21-25, 2012 CL San Diego, CA C1 [Kant, Ashima K.] CUNY, Queens Coll, FNES, Flushing, NY USA. [Graubard, Barry I.] NCI, Biostat Branch, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR PY 2012 VL 26 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 032IZ UT WOS:000310711306234 ER PT J AU Kaur, S Kuznetsova, SA Pendrak, ML Sipes, JM Roberts, DD AF Kaur, Sukhbir Kuznetsova, Svetlana A. Pendrak, Michael L. Sipes, John M. Roberts, David D. TI Thrombospondin-1 signaling via CD47 regulates T lymphocyte glycosaminoglycan biosynthesis SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology Meeting CY APR 21-25, 2012 CL San Diego, CA C1 [Kaur, Sukhbir; Kuznetsova, Svetlana A.; Pendrak, Michael L.; Sipes, John M.; Roberts, David D.] NIH, Pathol Lab, Bethesda, MD 20892 USA. RI Roberts, David/A-9699-2008 OI Roberts, David/0000-0002-2481-2981 NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR PY 2012 VL 26 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 032IZ UT WOS:000310711302638 ER PT J AU Kelly, A Shewmaker, F Wickner, R AF Kelly, Amy Shewmaker, Frank Wickner, Reed TI Molecular Analysis of Genetic Variation in Prions of Saccharomyces cerevisiae SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology Meeting CY APR 21-25, 2012 CL San Diego, CA C1 [Kelly, Amy; Wickner, Reed] NIDDK, NIH, Bethesda, MD USA. [Shewmaker, Frank] Uniformed Serv Univ Hlth Sci, Dept Pharmacol, Bethesda, MD 20814 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR PY 2012 VL 26 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 032IZ UT WOS:000310711304834 ER PT J AU Khan, FA Szabo-Fresnais, N Krall, J Moss, J Vaughan, M Movsesian, M Manganiello, V AF Khan, Faiyaz Ahmad Szabo-Fresnais, Nicolas Krall, Judy Moss, Joel Vaughan, Martha Movsesian, Matthew Manganiello, Vincent TI PKA-induced Interaction of Phosphorylated PDE3A (pPDE3A) and BIG1 (Brefeldin A-inhibited guanine nucleotide exchange protein 1) in Cytosolic Fractions from Human Myocardium may be Important in Regulation of BIG1 Function SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology Meeting CY APR 21-25, 2012 CL San Diego, CA C1 [Khan, Faiyaz Ahmad; Moss, Joel; Vaughan, Martha; Manganiello, Vincent] NHLBI, NIH, CPB, Bethesda, MD 20892 USA. [Szabo-Fresnais, Nicolas; Krall, Judy; Movsesian, Matthew] Univ Utah, Div Cardiol, Salt Lake City, UT 84112 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR PY 2012 VL 26 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 032IZ UT WOS:000310711305498 ER PT J AU Kim, EK Kim, YS Yu, LL Milner, JA Wang, TTY AF Kim, Eun-Kyung Kim, Young S. Yu, Liangli Milner, John A. Wang, Thomas T. Y. TI Broccoli-derived compounds modulate androgen up-regulation of C-C chemokine ligand 2 and enhancement of monocyte attraction to prostate cancer cells SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology Meeting CY APR 21-25, 2012 CL San Diego, CA C1 [Kim, Eun-Kyung; Yu, Liangli] Univ Maryland, College Pk, MD 20742 USA. [Kim, Young S.; Milner, John A.] NCI, Nutr Sci Res Grp, Rockville, MD USA. [Wang, Thomas T. Y.] ARS, Diet Genom & Immunol Lab, USDA, Beltsville, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR PY 2012 VL 26 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 032IZ UT WOS:000310711304484 ER PT J AU Kimura, AK Kim, HY AF Kimura, Atsuko Kakio Kim, Hee-Yong TI Acyl chain dependent product inhibition by phosphatidylserine synthases SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology Meeting CY APR 21-25, 2012 CL San Diego, CA C1 [Kimura, Atsuko Kakio; Kim, Hee-Yong] NIAAA, NIH, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR PY 2012 VL 26 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 032IZ UT WOS:000310711306538 ER PT J AU Kobilo, T van Praag, H AF Kobilo, Tali van Praag, Henriette TI Cognitive and motor effects of endurance related compound AICAR: from muscle to brain SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology Meeting CY APR 21-25, 2012 CL San Diego, CA C1 [Kobilo, Tali; van Praag, Henriette] NIA, Baltimore, MD 21224 USA. NR 0 TC 0 Z9 0 U1 1 U2 4 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR PY 2012 VL 26 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 032IZ UT WOS:000310711300384 ER PT J AU Kochukov, MY Balasubramanian, A Abramowitz, J Birnbaumer, L Marrelli, SP AF Kochukov, Mikhail Y. Balasubramanian, Adithya Abramowitz, Joel Birnbaumer, Lutz Marrelli, Sean P. TI Role of TRPC1 and TRPC3 channels in constriction and relaxation of mouse thoracic aorta SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology Meeting CY APR 21-25, 2012 CL San Diego, CA C1 [Kochukov, Mikhail Y.; Balasubramanian, Adithya; Marrelli, Sean P.] Baylor Coll Med, Houston, TX 77030 USA. [Abramowitz, Joel; Birnbaumer, Lutz] NIEHS, Res Triangle Pk, NC 27709 USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR PY 2012 VL 26 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 032IZ UT WOS:000310711305093 ER PT J AU Kraft, ML Klitzing, HA Lou, KY Zimmerberg, J Weber, PK AF Kraft, Mary L. Klitzing, Haley A. Lou, Kaiyan Zimmerberg, Joshua Weber, Peter K. TI Time-dependent changes in long range sphingolipid organization revealed by high-resolution secondary ion mass spectrometry SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology Meeting CY APR 21-25, 2012 CL San Diego, CA C1 [Kraft, Mary L.; Lou, Kaiyan] Univ Illinois, Dept Chem & Biomol Engn, Urbana, IL 61801 USA. [Kraft, Mary L.; Klitzing, Haley A.] Univ Illinois, Dept Chem, Urbana, IL 61801 USA. [Zimmerberg, Joshua] NICHHD, NIH, Bethesda, MD 20892 USA. [Weber, Peter K.] Lawrence Livermore Natl Lab, Glenn T Seaborg Inst, Livermore, CA USA. RI Lou, Kaiyan/D-4199-2012 OI Lou, Kaiyan/0000-0003-3443-0343 NR 0 TC 0 Z9 0 U1 0 U2 2 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR PY 2012 VL 26 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 032IZ UT WOS:000310711307263 ER PT J AU Kraft, ML Frisz, JF Klitzing, HA Lou, KY Lizunov, V Zimmerberg, J Weber, PK AF Kraft, Mary L. Frisz, Jessica F. Klitzing, Haley A. Lou, Kaiyan Lizunov, Vladimir Zimmerberg, Joshua Weber, Peter K. TI Chemical Imaging of Cholesterol and Sphingolipid Distribution in the Plasma Membranes of Fibroblast Cells SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology Meeting CY APR 21-25, 2012 CL San Diego, CA C1 [Kraft, Mary L.; Lou, Kaiyan] Univ Illinois, Dept Chem & Biomol Engn, Urbana, IL 61801 USA. [Frisz, Jessica F.; Klitzing, Haley A.] Univ Illinois, Dept Chem, Urbana, IL 61801 USA. [Lizunov, Vladimir; Zimmerberg, Joshua] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, NIH, Bethesda, MD USA. [Weber, Peter K.] Lawrence Livermore Natl Lab, Glenn T Seaborg Inst, Livermore, CA USA. RI Lou, Kaiyan/D-4199-2012 OI Lou, Kaiyan/0000-0003-3443-0343 NR 0 TC 0 Z9 0 U1 0 U2 10 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR PY 2012 VL 26 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 032IZ UT WOS:000310711307173 ER PT J AU Labrique, AB Klein, S Kmush, B Ali, H Engle, R Schulze, K Purcell, R West, KP Nelson, KE AF Labrique, Alain Bernard Klein, Sabra Kmush, Brittany Ali, Hasmot Engle, Ronald Schulze, Kerry Purcell, Robert West, Keith P., Jr. Nelson, Kenrad E. TI IMMUNOLOGIC DYSREGULATION AND MICRONUTRIENT DEFICIENCIES ASSOCIATED WITH RISK OF INTRAPARTUM HEPATITIS E INFECTIONS IN PREGNANT BANGLADESHI WOMEN SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology Meeting CY APR 21-25, 2012 CL San Diego, CA C1 [Labrique, Alain Bernard; Klein, Sabra; Kmush, Brittany; Schulze, Kerry; West, Keith P., Jr.; Nelson, Kenrad E.] Johns Hopkins Bloomberg Sch Publ Hlth, Baltimore, MD USA. [Ali, Hasmot] Johns Hopkins Univ Bangladesh, JiVitA Maternal & Child Res Project, Gaibandha, Bangladesh. [Engle, Ronald; Purcell, Robert] NIH, Hepatitis Viruses Sect, Infect Dis Lab, Rockville, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR PY 2012 VL 26 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 032IZ UT WOS:000310711306802 ER PT J AU Lal, A Thomas, M Navarro, F Li, XL Lieberman, J AF Lal, Ashish Thomas, Marshall Navarro, Francisco Li, Xiao Ling Lieberman, Judy TI A microRNA pulldown approach uncovers regulation of p53 activity and growth factor signaling by miR-34a SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology Meeting CY APR 21-25, 2012 CL San Diego, CA C1 [Lal, Ashish] NCI, Genet Branch, NIH, Bethesda, MD 20892 USA. [Thomas, Marshall; Navarro, Francisco; Lieberman, Judy] Harvard Univ, Sch Med, Boston, MA USA. RI Lieberman, Judy/A-2717-2015 NR 0 TC 0 Z9 0 U1 0 U2 5 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR PY 2012 VL 26 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 032IZ UT WOS:000310711300364 ER PT J AU Le, K Pacheco-Rodriguez, G Moss, J Vaughan, M AF Le, Kang Pacheco-Rodriguez, Gustavo Moss, Joel Vaughan, Martha TI Tripartite motif protein 23 (TRIM23) regulates degradation of epidermal growth factor receptor (EGFR) SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology Meeting CY APR 21-25, 2012 CL San Diego, CA C1 [Le, Kang; Pacheco-Rodriguez, Gustavo; Moss, Joel; Vaughan, Martha] NHLBI, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR PY 2012 VL 26 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 032IZ UT WOS:000310711302949 ER PT J AU Lezin, G Kosaka, Y Yost, HJ Kuehn, MR Brunelli, L AF Lezin, George Kosaka, Yasuhiro Yost, H. Joseph Kuehn, Michael R. Brunelli, Luca TI Differentiating frequency of recombination from frequency of recombinants SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology Meeting CY APR 21-25, 2012 CL San Diego, CA C1 [Lezin, George; Kosaka, Yasuhiro; Yost, H. Joseph; Brunelli, Luca] Univ Utah, Salt Lake City, UT USA. [Kuehn, Michael R.] NCI, Canc Res Ctr, Frederick, MD 21701 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR PY 2012 VL 26 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 032IZ UT WOS:000310711301203 ER PT J AU Lezin, G Kosaka, Y Yost, HJ Kuehn, MR Brunelli, L AF Lezin, George Kosaka, Yasuhiro Yost, H. Joseph Kuehn, Michael R. Brunelli, Luca TI A novel approach to isolate unselected recombinants facilitates markerless DNA recombineering SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology Meeting CY APR 21-25, 2012 CL San Diego, CA C1 [Lezin, George; Kosaka, Yasuhiro; Yost, H. Joseph; Brunelli, Luca] Univ Utah, Salt Lake City, UT USA. [Kuehn, Michael R.] NCI, Ctr Canc Res, Frederick, MD 21701 USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR PY 2012 VL 26 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 032IZ UT WOS:000310711301185 ER PT J AU Li, CC Shen, XY Aponte, A Shen, RF Billings, EM Moss, J Vaughan, M AF Li, Chun-Chun Shen, Xiaoyan Aponte, Angel Shen, Rong-Fong Billings, Eric M. Moss, Joel Vaughan, Martha TI BIG2, an ARF guanine nucleotide-exchange protein, regulates cell migration via effects integrin beta 1 cycling and actin cytoskeleton remodeling SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology Meeting CY APR 21-25, 2012 CL San Diego, CA C1 [Li, Chun-Chun; Shen, Xiaoyan; Moss, Joel; Vaughan, Martha] NHLBI, Cardiovasc & Pulm Branch, Bethesda, MD 20892 USA. [Aponte, Angel; Shen, Rong-Fong; Billings, Eric M.] NHLBI, Prote Core Facil, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR PY 2012 VL 26 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 032IZ UT WOS:000310711302765 ER PT J AU Li, HY Tu, HB Wang, YH Levine, M AF Li, Hongyan Tu, Hongbin Wang, Yaohui Levine, Mark TI Assay of Vitamin C in Red Blood Cells SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology Meeting CY APR 21-25, 2012 CL San Diego, CA C1 [Li, Hongyan; Tu, Hongbin; Wang, Yaohui; Levine, Mark] NIDDK, NIH, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR PY 2012 VL 26 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 032IZ UT WOS:000310711303243 ER PT J AU Lyon, AM Tesmer, VM Boguth, CA Dhamsania, VD Thal, DM Guiterrez, J Chowdhury, S Northup, JK Tesmer, JJG AF Lyon, Angeline Marie Tesmer, Valerie M. Boguth, Cassandra A. Dhamsania, Vishan D. Thal, David M. Guiterrez, Joanne Chowdhury, Shoaib Northup, John K. Tesmer, John J. G. TI How G alpha(q) Regulates PIP2 Hydrolysis: Molecular Mechanisms and Prospects for Drug Development SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology Meeting CY APR 21-25, 2012 CL San Diego, CA C1 [Lyon, Angeline Marie; Tesmer, Valerie M.; Boguth, Cassandra A.; Dhamsania, Vishan D.; Thal, David M.; Tesmer, John J. G.] Univ Michigan, Life Sci Inst, Ann Arbor, MI 48109 USA. [Guiterrez, Joanne; Chowdhury, Shoaib; Northup, John K.] NIDCD, NIH, Rockville, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR PY 2012 VL 26 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 032IZ UT WOS:000310711301100 ER PT J AU Malicdan, MC Momma, K Nishino, I Noguchi, S AF Malicdan, May Christine Momma, Kazunari Nishino, Ichizo Noguchi, Satoru TI Identification of biomarkers for GNE myopathy SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology Meeting CY APR 21-25, 2012 CL San Diego, CA C1 [Malicdan, May Christine] NHGRI, Med Genet Branch, NIH, Bethesda, MD 20892 USA. [Malicdan, May Christine; Momma, Kazunari; Nishino, Ichizo; Noguchi, Satoru] Natl Inst Neurosci, Dept Neuromuscular Res, Tokyo, Japan. [Momma, Kazunari] Natl Def Med Coll, Dept Neurol, Saitama, Japan. RI Malicdan, May Christine/F-2806-2013 NR 0 TC 0 Z9 0 U1 0 U2 1 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR PY 2012 VL 26 PG 2 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 032IZ UT WOS:000310711306981 ER PT J AU Manjerovic, MB Green, ML Kelly, AC Mateus-Pinilla, NE Shelton, P Novakofski, J AF Manjerovic, Mary Beth Green, Michelle L. Kelly, Amy C. Mateus-Pinilla, Nohra E. Shelton, Paul Novakofski, Jan TI Spatial variation in susceptibility to chronic wasting disease in white-tailed deer SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology Meeting CY APR 21-25, 2012 CL San Diego, CA C1 [Manjerovic, Mary Beth; Green, Michelle L.; Mateus-Pinilla, Nohra E.] Univ Illinois, Illinois Nat Hist Survey, Champaign, IL 61820 USA. [Manjerovic, Mary Beth; Green, Michelle L.; Kelly, Amy C.; Novakofski, Jan] Univ Illinois, Urbana, IL 61801 USA. [Kelly, Amy C.] NIDDK, NIH, Bethesda, MD USA. [Shelton, Paul] Illinois Dept Nat Resources, Div Wildlife Resources, Springfield, IL USA. NR 0 TC 0 Z9 0 U1 0 U2 9 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR PY 2012 VL 26 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 032IZ UT WOS:000310711305776 ER PT J AU Mashimo, M Niere, M Agledal, L Dolle, C Kasamatsu, A Kato, J Moss, J Ziegler, M AF Mashimo, Masato Niere, Marc Agledal, Line Dolle, Christian Kasamatsu, Atsushi Kato, Jiro Moss, Joel Ziegler, Mathias TI ARH3 catalyzes degradation of mitochondrial matrix-accumulated Poly (ADP-ribose) SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology Meeting CY APR 21-25, 2012 CL San Diego, CA C1 [Mashimo, Masato; Kasamatsu, Atsushi; Kato, Jiro; Moss, Joel] NHLBI, Cardiovasc & Pulm Branch, NIH, Bethesda, MD 20892 USA. [Niere, Marc; Agledal, Line; Dolle, Christian; Ziegler, Mathias] Univ Bergen, Dept Mol Biol, Bergen, Norway. NR 0 TC 0 Z9 0 U1 0 U2 1 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR PY 2012 VL 26 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 032IZ UT WOS:000310711303055 ER PT J AU McCarthy, P Saksena, R Peterson, D Lee, CH An, YM Vionnet, J Cipollo, J Vann, W AF McCarthy, Pumtiwitt Saksena, Rina Peterson, Dwight Lee, Che-Hung An, Yanming Vionnet, Justine Cipollo, John Vann, Willie TI Towards a Well Defined Meningitis Vaccine: Chemoenzymatic Synthesis of Meningococcal Glycoconjugate Vaccine Candidates SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology Meeting CY APR 21-25, 2012 CL San Diego, CA C1 [McCarthy, Pumtiwitt] NIH NIGMS, Bethesda, MD USA. [McCarthy, Pumtiwitt; Saksena, Rina; Peterson, Dwight; Lee, Che-Hung; An, Yanming; Vionnet, Justine; Cipollo, John; Vann, Willie] CBER FDA, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR PY 2012 VL 26 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 032IZ UT WOS:000310711305767 ER PT J AU Mereu, M Chun, LE Hiranita, T Cao, JJ Newman, A Katz, JL Tanda, G AF Mereu, Maddalena Chun, Lauren E. Hiranita, Takato Cao, Jian Jing Newman, Amy Katz, Jonathan L. Tanda, Gianluigi TI Rimcazole Attenuates the Cocaine-Induced Stimulation of Mesolimbic Dopamine related to its Abuse and Dependence SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology Meeting CY APR 21-25, 2012 CL San Diego, CA C1 [Mereu, Maddalena; Hiranita, Takato; Cao, Jian Jing; Newman, Amy; Katz, Jonathan L.; Tanda, Gianluigi] NIDA, Mol Targets & Medicat Discovery Branch, NIH, Baltimore, MD USA. [Chun, Lauren E.] Univ Colorado, Spencer Neuroendocrinol Lab, Boulder, CO 80309 USA. RI Tanda, Gianluigi/B-3318-2009; Hiranita, Takato/G-6567-2011 OI Tanda, Gianluigi/0000-0001-9526-9878; NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR PY 2012 VL 26 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 032IZ UT WOS:000310711305409 ER PT J AU Midthune, DN Carroll, RJ Subar, AF Freedman, LS Thompson, FE Kipnis, V AF Midthune, Douglas Neil Carroll, Raymond J. Subar, Amy F. Freedman, Laurence S. Thompson, Frances E. Kipnis, Victor TI Combining self-report dietary assessment instruments to reduce the effects of measurement error SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology Meeting CY APR 21-25, 2012 CL San Diego, CA C1 [Midthune, Douglas Neil; Kipnis, Victor] NCI, Canc Prevent Div, Biometry Res Grp, Bethesda, MD 20892 USA. [Subar, Amy F.; Thompson, Frances E.] NCI, Div Canc Control & Populat Sci, Risk Factor Monitoring & Methods Branch, Bethesda, MD 20892 USA. [Carroll, Raymond J.] Texas A&M Univ, Dept Stat, College Stn, TX 77843 USA. [Freedman, Laurence S.] Gertner Inst Epidemiol & Publ Hlth Policy, Biostat Unit, Tel Hashomer, Israel. NR 0 TC 0 Z9 0 U1 1 U2 7 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR PY 2012 VL 26 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 032IZ UT WOS:000310711305805 ER PT J AU Miller, DS Schroeter, C Wang, XQ Campos, CR AF Miller, David S. Schroeter, Christian Wang, Xueqian Campos, Christopher R. TI ABC Transporter Expression, Function and Regulation at the Blood-Spinal Cord Barrier SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology Meeting CY APR 21-25, 2012 CL San Diego, CA C1 [Miller, David S.; Wang, Xueqian; Campos, Christopher R.] NIEHS, Lab Toxicol & Pharmacol, NIH, Res Triangle Pk, NC 27709 USA. [Schroeter, Christian] Univ Heidelberg, Heidelberg, Germany. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR PY 2012 VL 26 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 032IZ UT WOS:000310711302473 ER PT J AU Miller, DS Campos, CR Hawkins, BT Cannon, R AF Miller, David S. Campos, Christopher R. Hawkins, Brian T. Cannon, Ronald TI Sphingolipids signal rapid loss of P-glycoprotein transport activity at the blood-brain barrier SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology Meeting CY APR 21-25, 2012 CL San Diego, CA C1 [Miller, David S.; Campos, Christopher R.; Cannon, Ronald] NIEHS, Lab Toxicol & Pharmacol, NIH, Res Triangle Pk, NC 27709 USA. [Hawkins, Brian T.] Univ Washington, Div Hematol, Sch Med, Seattle, WA 98195 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR PY 2012 VL 26 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 032IZ UT WOS:000310711300902 ER PT J AU Miller, TW Song, T Amarnath, S Fowler, DH Roberts, DD AF Miller, Thomas W. Song, Timothy Amarnath, Shoba Fowler, Daniel H. Roberts, David D. TI Hydrogen sulfide (H2S) regulates hypoxic signaling in T cells. SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology Meeting CY APR 21-25, 2012 CL San Diego, CA C1 [Miller, Thomas W.; Song, Timothy; Roberts, David D.] NCI, Pathol Lab, Bethesda, MD 20892 USA. RI Roberts, David/A-9699-2008 OI Roberts, David/0000-0002-2481-2981 NR 0 TC 0 Z9 0 U1 0 U2 2 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR PY 2012 VL 26 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 032IZ UT WOS:000310711303260 ER PT J AU Mizrahi, V Warner, D Ndwandwe, D Abrahams, G Venclovas, C AF Mizrahi, Valerie Warner, Digby Ndwandwe, Duduzile Abrahams, Garth Venclovas, Ceslovas TI A novel inducible mutagenesis system in Mycobacterium tuberculosis SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology Meeting CY APR 21-25, 2012 CL San Diego, CA C1 [Mizrahi, Valerie; Warner, Digby; Abrahams, Garth] Univ Cape Town, Inst Infect Dis & Mol Med, ZA-7925 Cape Town, South Africa. [Ndwandwe, Duduzile] Univ Witwatersrand, Ctr Excellence Biomed TB Res, Johannesburg, South Africa. [Abrahams, Garth] NIAID, TB Res Sect, Lab CLin Infect Dis, Bethesda, MD 20892 USA. [Venclovas, Ceslovas] Inst Biotechnol, Lab Bioinformat, Vilnius, Lithuania. NR 0 TC 0 Z9 0 U1 0 U2 4 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR PY 2012 VL 26 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 032IZ UT WOS:000310711300201 ER PT J AU Murray, DR Valente, AJ Siebenlist, U Chandrasekar, B AF Murray, David R. Valente, Anthony J. Siebenlist, Ulrich Chandrasekar, Bysani TI CIKS is critical mediator of isoproterenol/beta-AR induced cardiomyocyte hypertrophy in vitro and in vivo SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology Meeting CY APR 21-25, 2012 CL San Diego, CA C1 [Murray, David R.] William S Middleton Mem Vet Adm Med Ctr, Madison, WI USA. [Valente, Anthony J.] Univ Texas HSC, San Antonio, TX USA. [Siebenlist, Ulrich] NIAID, Lab Immunoregulat, NIH, Bethesda, MD 20892 USA. [Chandrasekar, Bysani] SLVHCS, New Orleans, LA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR PY 2012 VL 26 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 032IZ UT WOS:000310711304479 ER PT J AU Nader, SH Blaylock, BL Wilson, WD Banala, A Newman, AH Nader, MA AF Nader, Susan H. Blaylock, B. L. Wilson, W. D. Banala, A. Newman, A. H. Nader, M. A. TI Characterization of Dopamine D3 receptor-selective compounds on unconditioned behaviors and food/drug choice in cocaine and methamphetamine self-administering rhesus monkeys SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology Meeting CY APR 21-25, 2012 CL San Diego, CA C1 [Nader, Susan H.; Blaylock, B. L.; Wilson, W. D.; Nader, M. A.] Wake Forest Sch Med, Winston Salem, NC USA. [Banala, A.; Newman, A. H.] NIDA IRP, Baltimore, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR PY 2012 VL 26 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 032IZ UT WOS:000310711301467 ER PT J AU Namaste, S Ashour, F Porter, A Raghavan, R Pilch, S Raiten, D AF Namaste, Sorrel Ashour, Fayrouz Porter, Alexandra Raghavan, Ramkripa Pilch, Susan Raiten, Daniel TI Effect modifiers for the safety and efficacy of iron intervention in the context of malaria: A review of data for an individual patient based meta-analysis SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology Meeting CY APR 21-25, 2012 CL San Diego, CA C1 [Namaste, Sorrel; Ashour, Fayrouz; Porter, Alexandra; Raghavan, Ramkripa; Raiten, Daniel] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, NIH, Bethesda, MD USA. [Pilch, Susan] Natl Inst Hlth Lib, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR PY 2012 VL 26 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 032IZ UT WOS:000310711304735 ER PT J AU Nanda, JS Munoz, A Saini, AK Hinnebusch, AG AF Nanda, Jagpreet Singh Munoz, Antonio Saini, Adesh K. Hinnebusch, Alan G. TI Coordinated movement of eukaryotic translation initiation factors 1, 1A, and 5 within the 43S ribosomal preinitiation complex (PIC) mediates the response to start codon recognition. SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology Meeting CY APR 21-25, 2012 CL San Diego, CA C1 [Nanda, Jagpreet Singh; Munoz, Antonio] Johns Hopkins Univ, Sch Med, Baltimore, MD USA. [Saini, Adesh K.] Shoolini Univ Biotechnol, Shimla, India. [Hinnebusch, Alan G.] NICHD, Lab Gene Regulat & Dev, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 2 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR PY 2012 VL 26 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 032IZ UT WOS:000310711300595 ER PT J AU Nayeem, MA Zeldin, DC Pradhan, I Mustafa, SJ Falck, JR Morisseau, C Marowsky, A AF Nayeem, Mohammed A. Zeldin, Darryl C. Pradhan, Isha Mustafa, S. Jamal Falck, John R. Morisseau, Christophe Marowsky, Anne TI Disruption of soluble epoxide hydrolase modulates adenosine-induced response: role of adenosine A2A receptor and cyp-epoxygenases SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology Meeting CY APR 21-25, 2012 CL San Diego, CA C1 [Nayeem, Mohammed A.; Pradhan, Isha; Mustafa, S. Jamal] W Virginia Univ, Ctr Cardiovasc & Resp Sci, Morgantown, WV 26506 USA. [Zeldin, Darryl C.] NIEHS, Div Intramural Res, NIH, Res Triangle Pk, NC 27709 USA. [Falck, John R.] UTSWMC, Dallas, TX USA. [Morisseau, Christophe] Univ Calif Davis, Dept Entomol, Davis, WV USA. [Marowsky, Anne] Univ Calif Davis, UCD Canc Ctr, Davis, WV USA. NR 0 TC 0 Z9 0 U1 0 U2 2 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR PY 2012 VL 26 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 032IZ UT WOS:000310711300295 ER PT J AU Nelson, SM Carlson, B Urban, J Lei, XG Hatfield, D Prabhu, KS AF Nelson, Shakira M. Carlson, Bradley Urban, Joseph Lei, Xingen Hatfield, Dolph Prabhu, K. Sandeep TI Selenoprotein induced M1 to M2 murine macrophage phenotype switching is imperative in helminth parasite clearance SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology Meeting CY APR 21-25, 2012 CL San Diego, CA C1 [Nelson, Shakira M.; Prabhu, K. Sandeep] Penn State Univ, University Pk, PA 16802 USA. [Carlson, Bradley; Hatfield, Dolph] NCI, Bethesda, MD 20892 USA. [Urban, Joseph] USDA, Beltsville, MD 20705 USA. [Lei, Xingen] Cornell Univ, Ithaca, NY USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR PY 2012 VL 26 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 032IZ UT WOS:000310711303681 ER PT J AU Ness, EC Lazrak, A Jackson, JM Garantziotis, S Matalon, S AF Ness, Emily Christine Lazrak, Ahmed Jackson, Justin M. Garantziotis, Stavros Matalon, Sadis TI Inhibition of Epithelial Sodium Channel Activity by Inter-alpha-Trypsin Inhibitor SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology Meeting CY APR 21-25, 2012 CL San Diego, CA C1 [Ness, Emily Christine; Lazrak, Ahmed; Jackson, Justin M.; Matalon, Sadis] Univ Alabama Birmingham, Birmingham, AL USA. [Garantziotis, Stavros] NIEHS, Clin Res Unit, Res Triangle Pk, NC 27709 USA. RI Garantziotis, Stavros/A-6903-2009 OI Garantziotis, Stavros/0000-0003-4007-375X NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR PY 2012 VL 26 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 032IZ UT WOS:000310711305518 ER PT J AU Noguchi, S Malicdan, MC Funato, F Nishino, I AF Noguchi, Satoru Malicdan, May Christine Funato, Fumiko Nishino, Ichizo TI Metabolic changes in sialic acid synthesis pathway in GNE-myopathy model mice with long-term sialic acid treatment SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology Meeting CY APR 21-25, 2012 CL San Diego, CA C1 [Noguchi, Satoru; Funato, Fumiko; Nishino, Ichizo] NCNP, Dept Neuromuscular Res, Natl Inst Neurosci, Tokyo, Japan. [Malicdan, May Christine] NHGRI, MGB, NIH, Bethesda, MD 20892 USA. RI Malicdan, May Christine/F-2806-2013 NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR PY 2012 VL 26 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 032IZ UT WOS:000310711306949 ER PT J AU Oubrahim, H Wong, A Wilson, B Chock, PB AF Oubrahim, Hammou Wong, Allison Wilson, Brenda Chock, P. Boon TI On the mechanism of Pasteurella multocida toxin (PMT) induced mitogenesis: mTOR mediated upregulation of survivin and aurora kinase B in cultured cells SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology Meeting CY APR 21-25, 2012 CL San Diego, CA C1 [Oubrahim, Hammou; Wong, Allison; Chock, P. Boon] NHLBI, Biochem Lab, BBC, NIH, Bethesda, MD 20892 USA. [Wilson, Brenda] Univ Illinois, Dept Microbiol, Urbana, IL USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR PY 2012 VL 26 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 032IZ UT WOS:000310711305352 ER PT J AU Pathan, AR Bowlin, BM Machaca, K Abramowitz, J Zheng, F Rusch, NJ AF Pathan, Asif R. Bowlin, Brandi M. Machaca, Khaled Abramowitz, Joel Zheng, Fang Rusch, Nancy J. TI Phenylephrine-induced current and vasoconstriction are blunted in mesenteric arteries of TRPC3 knockout mice SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology Meeting CY APR 21-25, 2012 CL San Diego, CA C1 [Pathan, Asif R.; Bowlin, Brandi M.; Zheng, Fang; Rusch, Nancy J.] Univ Arkansas Med Sci, Little Rock, AR 72205 USA. [Machaca, Khaled] Weill Cornell Med Coll Qatar, Doha, Qatar. [Abramowitz, Joel] NIEHS, Lab Neurobiol, Div Intramural Res, Res Triangle Pk, NC 27709 USA. NR 0 TC 0 Z9 0 U1 0 U2 4 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR PY 2012 VL 26 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 032IZ UT WOS:000310711304530 ER PT J AU Patial, S Stumpo, DJ Lai, WS Ward, TW Blackshear, PJ AF Patial, Sonika Stumpo, Deborah J. Lai, Wi S. Ward, Toni W. Blackshear, Perry J. TI Genetic deletion of an instability motif in the Tristetraprolin (TTP) transcript: Implications for the treatment of systemic inflammation SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology Meeting CY APR 21-25, 2012 CL San Diego, CA C1 [Patial, Sonika; Stumpo, Deborah J.; Lai, Wi S.; Ward, Toni W.; Blackshear, Perry J.] NIEHS, LST, Durham, NC USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR PY 2012 VL 26 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 032IZ UT WOS:000310711304454 ER PT J AU Pradhan, I Mustafa, SJ Zeldin, DC Ledent, C Falck, JR Nayeem, MA AF Pradhan, Isha Mustafa, S. Jamal Zeldin, Darryl C. Ledent, Catherine Falck, J. R. Nayeem, Mohammed A. TI Salt modulates vascular response through cyp-epoxygenases in the presence of A(2A) AR SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology Meeting CY APR 21-25, 2012 CL San Diego, CA C1 [Pradhan, Isha; Mustafa, S. Jamal; Nayeem, Mohammed A.] W Virginia Univ, Morgantown, WV 26506 USA. [Zeldin, Darryl C.] NIEHS, Div Pulm, NIH, Res Triangle Pk, NC 27709 USA. [Ledent, Catherine] Univ Libre Brussels, IRIBHN, B-1070 Brussels, Belgium. [Falck, J. R.] Univ Texas Dallas, Dallas, TX 75230 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR PY 2012 VL 26 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 032IZ UT WOS:000310711304880 ER PT J AU Qu, AJ Li, F Krausz, K Shah, YM Gonzalez, FJ AF Qu, Aijuan Li, Fei Krausz, Kristopher Shah, Yatrik M. Gonzalez, Frank J. TI Metabolomics Reveals the role of hypoxia-inducible factors in hypoxia-induced liver metabolic shift SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology Meeting CY APR 21-25, 2012 CL San Diego, CA C1 [Qu, Aijuan; Li, Fei; Krausz, Kristopher; Gonzalez, Frank J.] NCI, Lab Metab, CCR, NIH, Bethesda, MD 20892 USA. [Shah, Yatrik M.] Univ Michigan, Sch Med, Dept Mol & Integrat Physiol, Ann Arbor, MI USA. RI Li, Fei/F-6849-2013 NR 0 TC 0 Z9 0 U1 0 U2 3 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR PY 2012 VL 26 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 032IZ UT WOS:000310711301726 ER PT J AU Raghavan, R Darnton-Hill, I Raiten, DJ AF Raghavan, Ramkripa Darnton-Hill, Ian Raiten, Daniel J. TI Biomarkers of Nutrition for Development (BOND): An Overview SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology Meeting CY APR 21-25, 2012 CL San Diego, CA C1 [Raghavan, Ramkripa; Raiten, Daniel J.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Endocrinol Nutr & Growth Branch, Bethesda, MD USA. [Darnton-Hill, Ian] Univ Sydney, Boden Inst Obes Nutr & Exercise, Sydney, NSW 2006, Australia. [Darnton-Hill, Ian] Tufts Univ, Friedman Sch Nutr Sci & Policy, Boston, MA 02111 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR PY 2012 VL 26 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 032IZ UT WOS:000310711305721 ER PT J AU Rahman, GM Sanker, S Lewin, N Prasad, BVV Blumberg, PM Das, J AF Rahman, Ghazi M. Sanker, Sreejesh Lewin, Nancy Prasad, B. V. V. Blumberg, Peter M. Das, Joydip TI Identification of the activator binding residues in protein kinase C theta C1B domain SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology Meeting CY APR 21-25, 2012 CL San Diego, CA C1 [Rahman, Ghazi M.; Das, Joydip] Univ Houston, Dept Pharmacol & Pharmaceut Sci, Houston, TX USA. [Sanker, Sreejesh; Prasad, B. V. V.] Baylor Coll Med, Dept Mol Virol & Microbiol, Houston, TX 77030 USA. [Lewin, Nancy; Blumberg, Peter M.] NCI, Lab Canc Biol & Genet, Ctr Canc Res, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR PY 2012 VL 26 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 032IZ UT WOS:000310711305724 ER PT J AU Rajagopal, V Park, EH Hinnebusch, AG Lorsch, JR AF Rajagopal, Vaishnavi Park, Eun-Hee Hinnebusch, Alan G. Lorsch, Jon R. TI Specific domains in yeast eukaryotic Initiation Factor (eIF) 4G bias the RNA unwinding specificity of eIF4F towards duplexes with a 5 '-overhang SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology Meeting CY APR 21-25, 2012 CL San Diego, CA C1 [Rajagopal, Vaishnavi; Lorsch, Jon R.] Johns Hopkins Univ, Sch Med, Baltimore, MD USA. [Park, Eun-Hee; Hinnebusch, Alan G.] NICHD, Program Cellular Regulat & Metab, NIH, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR PY 2012 VL 26 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 032IZ UT WOS:000310711300777 ER PT J AU Reece, KM Richardson, ED Pisle, ST Holly, AJ Campbell, TJ Figg, WD AF Reece, Kelie M. Richardson, Emily D. Pisle, Stephen T. Holly, Alesia J. Campbell, Tessa J. Figg, William D. TI Disruption of the HIF-1 alpha/p300 interaction as a means of inhibiting angiogenesis SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology Meeting CY APR 21-25, 2012 CL San Diego, CA C1 [Reece, Kelie M.; Richardson, Emily D.; Holly, Alesia J.; Campbell, Tessa J.; Figg, William D.] NCI, Med Oncol Branch, Bethesda, MD 20892 USA. [Pisle, Stephen T.] NCI, Clin Pharmacol Program, SAIC Frederick, Frederick, MD 21701 USA. RI Figg Sr, William/M-2411-2016 NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR PY 2012 VL 26 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 032IZ UT WOS:000310711303517 ER PT J AU Rhee, DK Hockman, SC Ahmad, F Manganiello, VC AF Rhee, Dong Keun Hockman, Steven Craig Ahmad, Faiyaz Manganiello, Vincent C. TI Heterologous expression of human phosphodiesterase 3A (hPDE3A) improves ethanol production in Saccharomyces cerevisiae SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology Meeting CY APR 21-25, 2012 CL San Diego, CA C1 [Rhee, Dong Keun; Hockman, Steven Craig; Ahmad, Faiyaz; Manganiello, Vincent C.] NHLBI, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR PY 2012 VL 26 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 032IZ UT WOS:000310711304721 ER PT J AU Rhee, DK Hockman, SC Manganiello, VC AF Rhee, Dong Keun Hockman, Steven Craig Manganiello, Vincent C. TI Heterologous expression of human phosphodiesterase 3A affects calcineurin-mediated calcium homeostasis in yeast SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology Meeting CY APR 21-25, 2012 CL San Diego, CA C1 [Rhee, Dong Keun; Hockman, Steven Craig; Manganiello, Vincent C.] NHLBI, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR PY 2012 VL 26 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 032IZ UT WOS:000310711304595 ER PT J AU Roof, RA Bergman, J Furman, CA Conroy, JL Mello, NK Skolnick, P Sibley, DR AF Roof, Rebecca A. Bergman, Jack Furman, Chersyse A. Conroy, Jennie L. Mello, Nancy K. Skolnick, Phil Sibley, David R. TI Buspirone is a potent antagonist at D-3 and D-4 Dopamine Receptors and attenuates the reinforcing effects of cocaine in a primate model SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology Meeting CY APR 21-25, 2012 CL San Diego, CA C1 [Roof, Rebecca A.; Conroy, Jennie L.; Sibley, David R.] NINDS, Mol Neuropharmacol Sect, NIH, Rockville, MD USA. [Bergman, Jack; Mello, Nancy K.] Harvard Univ, McLean Hosp, Sch Med, Belmont, MA USA. [Furman, Chersyse A.] NIH, Off Sci Policy Anal, Rockville, MD USA. [Skolnick, Phil] NIDA, NIH, Rockville, MD USA. NR 0 TC 0 Z9 0 U1 1 U2 4 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR PY 2012 VL 26 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 032IZ UT WOS:000310711300539 ER PT J AU Saito, K Moore, R Negishi, M AF Saito, Kosuke Moore, Rick Negishi, Masahiko TI p38 MAPK signaling determines CAR-mediated activation of the CYP2B genes by xenobiotics SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology Meeting CY APR 21-25, 2012 CL San Diego, CA C1 [Saito, Kosuke; Moore, Rick; Negishi, Masahiko] NIEHS, LRDT, Res Triangle Pk, NC 27709 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR PY 2012 VL 26 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 032IZ UT WOS:000310711302972 ER PT J AU Saldanha, LG Dwyer, JT Holden, JM Andrews, KW Bailey, RL Betz, JM Gahche, JJ Hardy, CJ Milner, J Roseland, JM AF Saldanha, Leila G. Dwyer, Johanna T. Holden, Joanne M. Andrews, Karen W. Bailey, Regan L. Betz, Joseph M. Gahche, Jaime J. Hardy, Constance J. Milner, John Roseland, Janet M. TI Identifying non-vitamin & mineral bioactive (non-VM) ingredients for inclusion in Dietary Supplement (DS) Composition Databases SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology Meeting CY APR 21-25, 2012 CL San Diego, CA C1 [Milner, John] NCI, NIH, Bethesda, MD 20892 USA. [Saldanha, Leila G.; Dwyer, Johanna T.; Bailey, Regan L.; Betz, Joseph M.] Off Dietary Supplements, Bethesda, MD USA. [Holden, Joanne M.; Andrews, Karen W.; Roseland, Janet M.] ARS, USDA, Beltsville, MD USA. [Gahche, Jaime J.] CDC, NHANES, NCHS, Hyattsville, MD USA. [Hardy, Constance J.] US FDA, CFSAN, College Pk, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 3 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR PY 2012 VL 26 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 032IZ UT WOS:000310711302966 ER PT J AU Samuel, W Kutty, RK Duncan, T Redmond, TM AF Samuel, William Kutty, R. Krishnan Duncan, Todd Redmond, T. Michael TI Endoplasmic reticulum stress induces the degradation of stearoyl-CoA desaturase protein in human retinal pigment epithelial cells via ubiquitin-proteasome pathway SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology Meeting CY APR 21-25, 2012 CL San Diego, CA C1 [Samuel, William; Kutty, R. Krishnan; Duncan, Todd; Redmond, T. Michael] NEI, LRCMB, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR PY 2012 VL 26 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 032IZ UT WOS:000310711300959 ER PT J AU Sankavaram, K Mattison, J de Cabo, R Pearson, K Allard, J AF Sankavaram, Kavitha Mattison, Julie de Cabo, Rafael Pearson, Kevin Allard, Joanne TI Resveratrol improves cerebrospinal fluid neuroprotective biomarkers in monkeys fed with a high-fat high-sugar diet SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology Meeting CY APR 21-25, 2012 CL San Diego, CA C1 [Sankavaram, Kavitha; Allard, Joanne] Howard Univ, Washington, DC 20059 USA. [Sankavaram, Kavitha; Mattison, Julie; de Cabo, Rafael] NIA, Lab Expt Biol, Baltimore, MD 21224 USA. [Pearson, Kevin] Univ Kentucky, Grad Ctr Nutr Sci, Lexington, KY USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR PY 2012 VL 26 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 032IZ UT WOS:000310711304717 ER PT J AU Schindler, C Baumann, MH Thorndike, EB Blough, BE Goldberg, SR AF Schindler, Charles Baumann, Michael H. Thorndike, Eric B. Blough, Bruce E. Goldberg, Steven R. TI Effects of 3,4-methylenedioxymethamphetamine (MDMA) and its metabolites on cardiovascular function in rats SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology Meeting CY APR 21-25, 2012 CL San Diego, CA C1 [Schindler, Charles; Baumann, Michael H.; Thorndike, Eric B.; Goldberg, Steven R.] NIH NIDA Intramural Reseach, Baltimore, MD USA. [Blough, Bruce E.] RTI Int, Res Triangle Pk, NC USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR PY 2012 VL 26 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 032IZ UT WOS:000310711303235 ER PT J AU Scoltock, AB Bortner, C Cidlowski, J AF Scoltock, Alyson Bell Bortner, Carl Cidlowski, John TI Signaling Mechanisms of Apoptosis Resistance in Lymphoid Cells Exposed to Hyperosmotic Stress SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology Meeting CY APR 21-25, 2012 CL San Diego, CA C1 [Scoltock, Alyson Bell; Bortner, Carl; Cidlowski, John] NIEHS, Lab Signal Transduct, NIH, DHHS, Res Triangle Pk, NC 27709 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR PY 2012 VL 26 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 032IZ UT WOS:000310711302699 ER PT J AU Sempos, CT Vesper, HW Phinney, K AF Sempos, Christopher T. Vesper, Hubert W. Phinney, Karen TI Vitamin D Standardization Program (VDSP) SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology Meeting CY APR 21-25, 2012 CL San Diego, CA C1 [Sempos, Christopher T.] NIH, Off Dietary Supplements, Bethesda, MD 20892 USA. [Vesper, Hubert W.] CSC, Div Sci Lab, Atlanta, GA USA. [Phinney, Karen] NIST, Div Analyt Chem, Gaithersburg, MD 20899 USA. NR 0 TC 0 Z9 0 U1 1 U2 3 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR PY 2012 VL 26 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 032IZ UT WOS:000310711301597 ER PT J AU Serafine, KM Briscione, MA Rice, KC Riley, AL AF Serafine, Katherine Marie Briscione, Maria A. Rice, Kenner C. Riley, Anthony L. TI Assessment of dopaminergic involvement in cocaine-induced conditioned taste aversions SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology Meeting CY APR 21-25, 2012 CL San Diego, CA C1 [Serafine, Katherine Marie; Briscione, Maria A.; Riley, Anthony L.] American Univ, Washington, DC 20016 USA. [Rice, Kenner C.] NIDA, Chem Biol Res Branch, Bethesda, MD 20892 USA. [Rice, Kenner C.] NIAAA, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR PY 2012 VL 26 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 032IZ UT WOS:000310711301132 ER PT J AU Shi, Y Alpatov, R Wagner, U Nakamoto-Kinoshita, M Ye, Z Luu, Y Armache, KJ Simon, MD Stuetzer, A Greer, EL Wang, ZB Hu, GQ Wu, FZ Xu, C Beavers, WN Guo, YH Bian, CB Morrison, PT Vakoc, CR Min, JR Fischle, W Kingston, RE Zhao, KJ Ren, B Warren, ST AF Shi, Yang Alpatov, Roman Wagner, Ulrich Nakamoto-Kinoshita, Mika Ye, Zhen Luu, Ying Armache, Karim J. Simon, Matthew D. Stuetzer, Alexandra Greer, Eric L. Wang, Zhibin Hu, Gang-Qing Wu, Feizhen Xu, Chao Beavers, William N. Guo, Yahong Bian, Chuanbing Morrison, Paul T. Vakoc, Christopher R. Min, Jinrong Fischle, Wolfgang Kingston, Robert E. Zhao, Keji Ren, Bing Warren, Stephen T. TI The fragile X mental retardation protein FMRP plays a role in the DNA damage response SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology Meeting CY APR 21-25, 2012 CL San Diego, CA C1 [Shi, Yang; Alpatov, Roman; Greer, Eric L.] Childrens Hosp, Boston, MA 02115 USA. [Shi, Yang; Alpatov, Roman; Greer, Eric L.] Harvard Univ, Sch Med, Boston, MA USA. [Wagner, Ulrich; Ye, Zhen; Luu, Ying; Ren, Bing] Univ Calif San Diego, Ludwig Inst Canc Res, La Jolla, CA 92093 USA. [Nakamoto-Kinoshita, Mika; Warren, Stephen T.] Emory Univ, Sch Med, Dept Human Genet, Atlanta, GA USA. [Nakamoto-Kinoshita, Mika; Warren, Stephen T.] Emory Univ, Sch Med, Dept Biochem, Atlanta, GA 30322 USA. [Nakamoto-Kinoshita, Mika; Warren, Stephen T.] Emory Univ, Sch Med, Dept Pediat, Atlanta, GA USA. [Armache, Karim J.; Simon, Matthew D.; Kingston, Robert E.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Stuetzer, Alexandra; Fischle, Wolfgang] Max Planck Inst Biol Chem, Gottingen, Germany. [Wang, Zhibin; Hu, Gang-Qing; Zhao, Keji] NHLBI, Lab Mol Immunol, NIH, Bethesda, MD 20892 USA. [Wu, Feizhen] Fudan Univ, Inst Biomed Sci, Shanghai 200433, Peoples R China. [Xu, Chao; Guo, Yahong; Bian, Chuanbing; Min, Jinrong] Univ Toronto, Struct Genom Consortium, Toronto, ON, Canada. [Beavers, William N.; Morrison, Paul T.] Dana Farber Canc Inst, Mol Biol Core Facil, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 1 U2 5 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR PY 2012 VL 26 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 032IZ UT WOS:000310711307045 ER PT J AU Shi, YB AF Shi, Yun-Bo TI Liganded thyroid hormone receptor induces nucleosome removal and histone modifications to activate transcription during adult stem cell development SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology Meeting CY APR 21-25, 2012 CL San Diego, CA C1 [Shi, Yun-Bo] NICHD, LGRD, NIH, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR PY 2012 VL 26 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 032IZ UT WOS:000310711300497 ER PT J AU Slezak, J Katz, JL AF Slezak, Jonathan Katz, Jonathan L. TI A comparison of methylphenidate enantiomers on delay discounting in rats SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology Meeting CY APR 21-25, 2012 CL San Diego, CA C1 [Slezak, Jonathan; Katz, Jonathan L.] NIDA IRP NIH, Baltimore, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR PY 2012 VL 26 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 032IZ UT WOS:000310711303110 ER PT J AU Song, WF Yu, ZH Ambalavanan, N Garantziotis, S Matalon, S AF Song, Weifeng Yu, Zhihong Ambalavanan, Namasivayam Garantziotis, Stavros Matalon, Sadis TI Respiratory Syncytial Virus Infections Augment Airway Reactivity in Mice Exposed to Chlorine (Cl-2) SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology Meeting CY APR 21-25, 2012 CL San Diego, CA C1 [Song, Weifeng; Yu, Zhihong; Ambalavanan, Namasivayam; Matalon, Sadis] Univ Alabama Birmingham, Birmingham, AL USA. [Garantziotis, Stavros] NIEHS, Clin Res Unit, Res Triangle Pk, NC USA. RI Garantziotis, Stavros/A-6903-2009 OI Garantziotis, Stavros/0000-0003-4007-375X NR 0 TC 0 Z9 0 U1 0 U2 1 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR PY 2012 VL 26 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 032IZ UT WOS:000310711305891 ER PT J AU Srivastava, S Kashiwaya, Y King, MT Baxa, U Tam, J Niu, G Chen, XY Clarke, K Veech, RL AF Srivastava, Shireesh Kashiwaya, Yoshihiro King, M. Todd Baxa, Ulrich Tam, Joseph Niu, Gang Chen, Xiaoyuan Clarke, Kieran Veech, Richard L. TI Mitochondrial Biogenesis and Increased Uncoupling Protein 1 in Brown Adipose Tissue of Mice Fed a Ketone Ester Diet SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology Meeting CY APR 21-25, 2012 CL San Diego, CA C1 [Srivastava, Shireesh; Kashiwaya, Yoshihiro; King, M. Todd; Veech, Richard L.] NIAAA, Lab Metab Control, Bethesda, MD 21701 USA. [Tam, Joseph] NIAAA, Lab Physiol Studies, Bethesda, MD USA. [Niu, Gang; Chen, Xiaoyuan] Natl Inst Biomed Imaging, Lab Mol Imaging & Nanomed LOMIN, NIH, Bethesda, MD USA. [Baxa, Ulrich] NCI, Adv Technol Program, Frederick, MD USA. [Clarke, Kieran] Univ Oxford, Dept Physiol Anat & Genet, Oxford, England. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR PY 2012 VL 26 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 032IZ UT WOS:000310711304691 ER PT J AU Steiner, J Davis, JM McClellan, J Green, J Murphy, EA AF Steiner, Jennifer Davis, J. Mark McClellan, Jamie Green, Jeffrey Murphy, E. Angela TI Quercetin decreases tumorigenesis in a high fat diet-enhanced mouse model of breast cancer SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology Meeting CY APR 21-25, 2012 CL San Diego, CA C1 [Murphy, E. Angela] Univ S Carolina, Sch Med, Columbia, SC USA. [Green, Jeffrey] NCI, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR PY 2012 VL 26 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 032IZ UT WOS:000310711302041 ER PT J AU Streater, C An, J Weng, NP AF Streater, Courtney An, Jie Weng, Nan Ping TI Posttranscriptional regulation of telomerase reverse transcriptase in Human T cells SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology Meeting CY APR 21-25, 2012 CL San Diego, CA C1 [Streater, Courtney] Univ Maryland Eastern Shore, Princess Anne, MD USA. [An, Jie; Weng, Nan Ping] NIA, Baltimore, MD 21224 USA. NR 0 TC 0 Z9 0 U1 0 U2 3 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR PY 2012 VL 26 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 032IZ UT WOS:000310711301036 ER PT J AU Subar, AF Kirkpatrick, SI Mittl, B Zimmerman, TP Thompson, FE Bingley, C Willis, G McNutt, S Potischman, N AF Subar, Amy F. Kirkpatrick, Sharon I. Mittl, Beth Zimmerman, Thea P. Thompson, Frances E. Bingley, Christopher Willis, Gordon McNutt, Suzanne Potischman, Nancy TI The National Cancer Institute's automated self-administered 24-hour dietary recall (ASA24) SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology Meeting CY APR 21-25, 2012 CL San Diego, CA C1 [Subar, Amy F.; Kirkpatrick, Sharon I.; Thompson, Frances E.; Willis, Gordon; Potischman, Nancy] NCI, Appl Res Program, Bethesda, MD 20892 USA. [Mittl, Beth; Zimmerman, Thea P.; Bingley, Christopher; McNutt, Suzanne] WESTAT Corp, Rockville, MD 20850 USA. NR 0 TC 0 Z9 0 U1 1 U2 4 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR PY 2012 VL 26 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 032IZ UT WOS:000310711302512 ER PT J AU Talan, MI Ahmet, I Lakatta, EG AF Talan, Mark I. Ahmet, Ismayil Lakatta, Edward G. TI Acute, NO-mediated, effects of erythropoietin are not associated with its cardioprotective properties SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology Meeting CY APR 21-25, 2012 CL San Diego, CA C1 [Talan, Mark I.; Ahmet, Ismayil; Lakatta, Edward G.] NIA, Cardiovasc Sci Lab, Baltimore, MD 21224 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR PY 2012 VL 26 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 032IZ UT WOS:000310711300553 ER PT J AU Tauseef, M Knezevic, N Chava, K Schraufnagel, D Smith, M Vogel, S Dietrich, A Birnbaumer, L Malik, A Mehta, D AF Tauseef, Mohammad Knezevic, Nebojsa Chava, Koteswara Schraufnagel, Dean Smith, Monica Vogel, Stephen Dietrich, Alexander Birnbaumer, Lutz Malik, Asrar Mehta, Dolly TI Cation channel TRPC6 activation of TLR4 in endothelial cells mediates sepsis-induced acute lung injury SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology Meeting CY APR 21-25, 2012 CL San Diego, CA C1 [Tauseef, Mohammad; Knezevic, Nebojsa; Chava, Koteswara; Schraufnagel, Dean; Smith, Monica; Vogel, Stephen; Malik, Asrar; Mehta, Dolly] Univ Illinois Chicago UIC, Chicago, IL USA. [Dietrich, Alexander] Walter Straub Inst Pharmacol & Toxicol, Munich, Germany. [Birnbaumer, Lutz] NIEHS, Res Triangle Pk, NC 27709 USA. RI Dietrich, Alexander/G-8619-2013 NR 0 TC 0 Z9 0 U1 0 U2 3 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR PY 2012 VL 26 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 032IZ UT WOS:000310711304270 ER PT J AU Tobe, R Naranjo-Suarez, S Turanov, AA Carlson, BA Tsuji, PA Yoo, MH Everley, RA Gladyshev, VN AF Tobe, Ryuta Naranjo-Suarez, Salvador Turanov, Anton A. Carlson, Bradley A. Tsuji, Petra A. Yoo, Min-Hyuk Everley, Robert A. Gladyshev, Vadim N. TI Antibiotics induce mistranslation of selenocysteine residue in selenoproteins SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology Meeting CY APR 21-25, 2012 CL San Diego, CA C1 [Tobe, Ryuta; Naranjo-Suarez, Salvador; Carlson, Bradley A.; Yoo, Min-Hyuk] NCI, NIH, Bethesda, MD 20892 USA. [Turanov, Anton A.; Everley, Robert A.; Gladyshev, Vadim N.] Brigham & Womens Hosp, Boston, MA 02115 USA. [Turanov, Anton A.; Everley, Robert A.; Gladyshev, Vadim N.] Harvard Univ, Sch Med, Boston, MA USA. [Tsuji, Petra A.] Towson Univ, Towson, MD USA. RI Gladyshev, Vadim/A-9894-2013 NR 0 TC 0 Z9 0 U1 0 U2 2 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR PY 2012 VL 26 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 032IZ UT WOS:000310711303157 ER PT J AU Tryba, AK Chong, JA Del Camino, D Lacey, V Abramowitz, J Birnbaumer, L Harder, DR Gerges, N Kaczorowski, CC AF Tryba, Andrew Kieran Chong, Jayhong A. Del Camino, D. Lacey, V. Abramowitz, Joel Birnbaumer, Lutz Harder, David R. Gerges, Nashaat Kaczorowski, Catherine C. TI Role of TRPC3 channels in BDNF-induced plasticity, hippocampal neuronal excitability and memory SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology Meeting CY APR 21-25, 2012 CL San Diego, CA C1 [Tryba, Andrew Kieran; Harder, David R.; Gerges, Nashaat; Kaczorowski, Catherine C.] Med Coll Wisconsin, Milwaukee, WI 53226 USA. [Chong, Jayhong A.; Del Camino, D.; Lacey, V.] Hydra Biosci, Cambridge, MA USA. [Abramowitz, Joel; Birnbaumer, Lutz] NIEHS, NIH, Res Triangle Pk, NC 27709 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR PY 2012 VL 26 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 032IZ UT WOS:000310711307022 ER PT J AU Tsuji, PA Carlson, BA Yoo, MH Xu, XM Naranjo-Suarez, S Davis, CD Gladyshev, VN Hatfield, DL AF Tsuji, Petra Akiko Carlson, Bradley A. Yoo, Min-Hyuk Xu, Xue-Ming Naranjo-Suarez, Salvador Davis, Cindy D. Gladyshev, Vadim N. Hatfield, Dolph L. TI Independent down-regulation of Sep15 and TR1, but not deficiency in both genes, affects cancer phenotypes of mouse colon carcinoma cells SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology Meeting CY APR 21-25, 2012 CL San Diego, CA C1 [Tsuji, Petra Akiko] Towson Univ, Towson, MD USA. [Carlson, Bradley A.; Yoo, Min-Hyuk; Xu, Xue-Ming; Naranjo-Suarez, Salvador; Hatfield, Dolph L.] NCI, MBSS, LCP, Bethesda, MD 20892 USA. [Davis, Cindy D.] NCI, NSRG, DCP, Bethesda, MD 20892 USA. [Gladyshev, Vadim N.] Brigham & Womens Hosp, Boston, MA 02115 USA. RI Gladyshev, Vadim/A-9894-2013 NR 0 TC 0 Z9 0 U1 0 U2 2 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR PY 2012 VL 26 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 032IZ UT WOS:000310711303061 ER PT J AU Turanov, AA Hatfield, DL Gladyshev, VN AF Turanov, Anton A. Hatfield, Dolph L. Gladyshev, Vadim N. TI SECIS- and UGA position-dependent incorporation of selenocysteine into mammalian selenoproteins SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology Meeting CY APR 21-25, 2012 CL San Diego, CA C1 [Turanov, Anton A.; Gladyshev, Vadim N.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Med,Div Genet 1, Boston, MA 02115 USA. [Hatfield, Dolph L.] NCI, Lab Canc Prevent, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. RI Gladyshev, Vadim/A-9894-2013 NR 0 TC 0 Z9 0 U1 1 U2 2 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR PY 2012 VL 26 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 032IZ UT WOS:000310711302178 ER PT J AU Turbyville, TJ Blonder, J Das, S Ye, XY Prieto, DA Veenstra, TD Milner, JA Romagnolo, DF AF Turbyville, Tommy J. Blonder, Josip Das, Sudipto Ye, Xiaoying Prieto, Darue A. Veenstra, Timothy D. Milner, John A. Romagnolo, Donato F. TI Comparative Proteomic Profiling of Human Breast Cell Lines SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology Meeting CY APR 21-25, 2012 CL San Diego, CA C1 [Turbyville, Tommy J.] SAIC NCI, Opt Microscopy & Anal Lab, Frederick, MD USA. [Blonder, Josip; Das, Sudipto; Ye, Xiaoying; Prieto, Darue A.; Veenstra, Timothy D.] SAIC NCI, Lab Prote & Analyt Technol, Adv Technol Program, Frederick, MD USA. [Milner, John A.] NCI, Canc Prevent Div, NIH, Rockville, MD USA. [Romagnolo, Donato F.] Univ Arizona, Dept Nutr Sci, Tucson, AZ USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR PY 2012 VL 26 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 032IZ UT WOS:000310711306383 ER PT J AU Ungvari, Z Bailey-Downs, LC Gautam, T Sosnowska, D Wang, MY Monticone, RE Telljohann, R de Cabo, R Sonntag, WE Lakatta, E Csiszar, A AF Ungvari, Zoltan Bailey-Downs, Lora C. Gautam, Tripti Sosnowska, Danuta Wang Mingyi Monticone, Robert E. Telljohann, Richard de Cabo, Rafael Sonntag, William E. Lakatta, Edward Csiszar, Anna TI Age-associated vascular oxidative stress, Nrf2 dysfunction and NF-kappa B activation in the non-human primate Macaca mulatta SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology Meeting CY APR 21-25, 2012 CL San Diego, CA C1 [Ungvari, Zoltan; Bailey-Downs, Lora C.; Gautam, Tripti; Sosnowska, Danuta; Sonntag, William E.; Csiszar, Anna] Univ Oklahoma, Hlth Sci Ctr, Reynolds Oklahoma Ctr Aging, Oklahoma City, OK USA. [Wang Mingyi; Monticone, Robert E.; Telljohann, Richard; de Cabo, Rafael; Lakatta, Edward] NIA, Baltimore, MD 21224 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR PY 2012 VL 26 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 032IZ UT WOS:000310711305123 ER PT J AU Wang, PM Martin, WJ AF Wang, Ping M. Martin, William J., II TI Evidence for proliferation of airway-delivered donor type II cells in lungs of recipient mice following intratracheal bleomycin SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology Meeting CY APR 21-25, 2012 CL San Diego, CA C1 [Wang, Ping M.; Martin, William J., II] NICHD, NIH, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR PY 2012 VL 26 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 032IZ UT WOS:000310711301007 ER PT J AU Yadav, H Quijano, C Kamaraju, AK Gavrilova, O Lonning, S Skarulis, M Sumner, AE Finkel, T Rane, SG AF Yadav, Hariom Quijano, Celia Kamaraju, Anil K. Gavrilova, Oksana Lonning, Scott Skarulis, Monica Sumner, Anne E. Finkel, Toren Rane, Sushil G. TI TGF-beta/Smad3 signaling inhibition protects from obesity and diabetes through modulation of adipocyte biology SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology Meeting CY APR 21-25, 2012 CL San Diego, CA C1 [Yadav, Hariom; Kamaraju, Anil K.; Skarulis, Monica; Sumner, Anne E.; Rane, Sushil G.] NIDDK, Diabet Endocrinol & Obes Branch, NIH, Bethesda, MD USA. [Quijano, Celia; Finkel, Toren] NHLBI, Ctr Mol Med, NIH, Bethesda, MD 20892 USA. [Gavrilova, Oksana] NIDDK, Mouse Metab Core Lab, NIH, Bethesda, MD USA. [Lonning, Scott] Genzyme Corp, Framingham, MA 01701 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR PY 2012 VL 26 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 032IZ UT WOS:000310711303518 ER PT J AU Yadav, H Rane, SG AF Yadav, Hariom Rane, Sushil G. TI Feeding of probiotic formulation protects from obesity and diabetes SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology Meeting CY APR 21-25, 2012 CL San Diego, CA C1 [Yadav, Hariom; Rane, Sushil G.] NIDDK, Endocrinol & Obes Branch, NIH, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 4 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR PY 2012 VL 26 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 032IZ UT WOS:000310711303475 ER PT J AU Yadav, H Rane, SG AF Yadav, Hariom Rane, Sushil G. TI Role of unique miRNAs in development of obesity and type 2 diabetes SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology Meeting CY APR 21-25, 2012 CL San Diego, CA C1 [Yadav, Hariom; Rane, Sushil G.] NIDDK, Diabet Endocrinol & Obes Branch, NIH, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR PY 2012 VL 26 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 032IZ UT WOS:000310711301131 ER PT J AU Yang, J Eliasson, B Smith, U Cushman, SW Sherman, A AF Yang, Jian Eliasson, Bjorn Smith, Ulf Cushman, Samuel W. Sherman, Arthur TI Amelioration of insulin resistance by rosiglitazone is associated with increased adipose cell size in obese type 2 diabetics SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology Meeting CY APR 21-25, 2012 CL San Diego, CA C1 [Yang, Jian] Univ S Alabama, Coll Med, Mobile, AL USA. [Yang, Jian; Cushman, Samuel W.] NIDDK, DEOB, NIH, Bethesda, MD USA. [Eliasson, Bjorn; Smith, Ulf] Univ Gothenburg, Sahlgrenska Univ Hosp, Gothenburg, Sweden. [Sherman, Arthur] NIDDK, LBM, NIH, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR PY 2012 VL 26 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 032IZ UT WOS:000310711303613 ER PT J AU Yang, Y Evans, S Escano, C Asico, L Zhang, YR Gonzalez, SC Villar, VA Wang, XY Pisegna, JR Wank, SA Armando, I Jose, P AF Yang, Yu Evans, Sarah Escano, Crisanto Asico, Laureano Zhang, Yanrong Gonzalez, Santiago Cuevas Villar, Van Anthony Wang, Xiaoyan Pisegna, Joseph R. Wank, Stephen A. Armando, Ines Jose, Pedro TI Expression of gastrin in the thin descending limb of Henle's loop in the mouse kidney: a molecular, localization, and functional study SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology Meeting CY APR 21-25, 2012 CL San Diego, CA C1 [Yang, Yu; Evans, Sarah; Escano, Crisanto; Asico, Laureano; Zhang, Yanrong; Gonzalez, Santiago Cuevas; Villar, Van Anthony; Wang, Xiaoyan; Armando, Ines; Jose, Pedro] George Washington Univ, Childrens Natl Med Ctr, Ctr Mol Physiol Res, Washington, DC USA. [Pisegna, Joseph R.] Univ Calif Los Angeles, Sch Med, Dept Med, Los Angeles, CA 90024 USA. [Wank, Stephen A.] NIDDK, Gastrointestinal Cell Biol Sect, NIH, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR PY 2012 VL 26 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 032IZ UT WOS:000310711304811 ER PT J AU Yazawa, I Yoshida, Y Yoshimi, R O'Donovan, M Ozato, K AF Yazawa, Itaru Yoshida, Yuko Yoshimi, Ryusuke O'Donovan, Michael Ozato, Keiko TI Electrophysiological analysis of the spinal network function in the in situ adult interferon regulatory factor 8 (IRF8) knockout mice SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology Meeting CY APR 21-25, 2012 CL San Diego, CA C1 [Yazawa, Itaru] Showa Univ, Dept Anat, Sch Med, Shinagawa, Japan. [Yazawa, Itaru; O'Donovan, Michael] NINDS, Bethesda, MD 20892 USA. [Yoshida, Yuko; Yoshimi, Ryusuke; Ozato, Keiko] NICHHD, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR PY 2012 VL 26 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 032IZ UT WOS:000310711304531 ER PT J AU Yoo, MH Carlson, BA Tsuji, PA Gladyshev, VN Hatfield, DL AF Yoo, Min-Hyuk Carlson, Bradley A. Tsuji, Petra A. Gladyshev, Vadim N. Hatfield, Dolph L. TI Thioredoxin reductase 1: Role in oxidative stress within cancer cells SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology Meeting CY APR 21-25, 2012 CL San Diego, CA C1 [Yoo, Min-Hyuk; Carlson, Bradley A.; Tsuji, Petra A.; Hatfield, Dolph L.] NCI, NIH, Bethesda, MD 20892 USA. [Gladyshev, Vadim N.] Brigham & Womens Hosp, Boston, MA 02115 USA. [Gladyshev, Vadim N.] Harvard Univ, Sch Med, Boston, MA USA. RI Gladyshev, Vadim/A-9894-2013 NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR PY 2012 VL 26 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 032IZ UT WOS:000310711303192 ER PT J AU Zhou, XM Burg, MB Ferraris, JD AF Zhou, Xiaoming Burg, Maurice B. Ferraris, Joan D. TI PTG (Protein Targeting to Glycogen) regulates the osmoprotective transcription factor NFAT5 via SHP-1 phosphatase SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology Meeting CY APR 21-25, 2012 CL San Diego, CA C1 [Zhou, Xiaoming] Uniformed Serv Univ Hlth Sci, Bethesda, MD 20814 USA. [Burg, Maurice B.; Ferraris, Joan D.] NHLBI, Syst Biol Ctr, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR PY 2012 VL 26 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 032IZ UT WOS:000310711300292 ER PT J AU Zwicker, JD Zhang, Y Hutchinson, MR Rice, KC Watkins, LR Funk, GD AF Zwicker, Jennifer D. Zhang, Yong Hutchinson, Mark R. Rice, Kenner C. Watkins, Linda R. Funk, Gregory D. TI Microglia attenuate the opioid-induced depression of preBotzinger Complex (preBotC) inspiratory rhythm in vitro via a TLR4-independent pathway SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology Meeting CY APR 21-25, 2012 CL San Diego, CA C1 [Zwicker, Jennifer D.; Zhang, Yong; Funk, Gregory D.] Univ Alberta, Dept Physiol, Edmonton, AB, Canada. [Hutchinson, Mark R.] Univ Adelaide, Dept Pharmacol, Adelaide, SA, Australia. [Rice, Kenner C.] NIDA, Chem Biol Res Branch, Bethesda, MD 20892 USA. [Watkins, Linda R.] Univ Colorado, Dept Psychol, Boulder, CO 80309 USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR PY 2012 VL 26 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 032IZ UT WOS:000310711305686 ER PT J AU Wang, Y Dinse, GE Rogan, WJ AF Wang, Y. Dinse, G. E. Rogan, W. J. TI Birth weight, early weight gain and pubertal maturation: a longitudinal study SO PEDIATRIC OBESITY LA English DT Article DE Age at menarche; birth weight; Tanner stage; weight gain ID POSTNATAL-GROWTH; DICHLORODIPHENYL DICHLOROETHENE; POLYCHLORINATED-BIPHENYLS; PROSPECTIVE COHORT; SEXUAL-MATURATION; CHILDHOOD GROWTH; US CHILDREN; BODY-SIZE; MENARCHE; AGE AB Objective: To investigate the effect of birth weight and early weight gain on the timing of various measures of puberty in both girls and boys. Methods: A total of 856 newborns enrolled in the North Carolina Infant Feeding Study were followed to age 5 years, with 600 children followed up at adolescence. Birth weight was obtained from medical records and children were weighed at study visits until age 5 years; gains in standardized weights were calculated over four early age intervals: 0-6 months, 6-12 months, 1-2 years and 2-5 years. Age at menarche in girls and age at advanced Tanner stages in both girls and boys were reported by adolescents and their parents. Survival models were used to analyse the effects of birth weight and early weight gain on these outcomes. esults: Girls with higher birth weight and greater weight gains during the four early age intervals were younger when they reached menarche and advanced Tanner stages; boys with greater early weight gains also were younger when they reached advanced Tanner stages, but few of these effects were statistically significant. Conclusions: Higher birth weights and greater weight gains during infancy and early childhood can lead to earlier sexual maturation in girls. C1 [Wang, Y.; Rogan, W. J.] NIEHS, Epidemiol Branch, Res Triangle Pk, NC 27709 USA. [Dinse, G. E.] NIEHS, Biostat Branch, Res Triangle Pk, NC 27709 USA. RP Wang, Y (reprint author), NIEHS, Epidemiol Branch, POB 12233,Mail Drop A3-05, Res Triangle Pk, NC 27709 USA. EM wangy13@niehs.nih.gov RI Rogan, Walter/I-6034-2012 OI Rogan, Walter/0000-0002-9302-0160 FU NIH, National Institute of Environmental Health Sciences FX This research was supported by the Intramural Research Program of the NIH, National Institute of Environmental Health Sciences. NR 38 TC 18 Z9 19 U1 3 U2 10 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 2047-6310 EI 2047-6302 J9 PEDIATR OBES JI Pediatr. Obes. PD APR PY 2012 VL 7 IS 2 BP 101 EP 109 DI 10.1111/j.2047-6310.2011.00022.x PG 9 WC Pediatrics SC Pediatrics GA 029SQ UT WOS:000310516400008 PM 22434749 ER PT J AU Hall, KD Heymsfield, SB Kemnitz, JW Klein, S Schoeller, DA Speakman, JR AF Hall, Kevin D. Heymsfield, Steven B. Kemnitz, Joseph W. Klein, Samuel Schoeller, Dale A. Speakman, John R. TI Energy balance and its components: implications for body weight regulation SO AMERICAN JOURNAL OF CLINICAL NUTRITION LA English DT Article ID PHYSICAL-ACTIVITY; METABOLIC-RATE; FOOD-INTAKE; EXPENDITURE; HUMANS; MEN; OBESE; GAIN; AGE C1 [Speakman, John R.] Univ Aberdeen, Inst Biol & Environm Sci, Aberdeen AB24 2TZ, Scotland. [Hall, Kevin D.] NIDDKD, NIH, Bethesda, MD 20892 USA. [Heymsfield, Steven B.] Pennington Biomed Res Ctr, Baton Rouge, LA USA. [Kemnitz, Joseph W.] Univ Wisconsin, Inst Clin & Translat Res, Madison, WI USA. [Klein, Samuel] Washington Univ, Sch Med, St Louis, MO USA. RP Speakman, JR (reprint author), Univ Aberdeen, Inst Biol & Environm Sci, Aberdeen AB24 2TZ, Scotland. EM j.speakman@abdn.ac.uk RI John, Speakman/A-9494-2008 OI John, Speakman/0000-0002-2457-1823 FU ILSI North America; Intramural Research Program of the NIH, National Institute of Diabetes and Digestive and Kidney Diseases FX This work was supported in part by an educational grant from ILSI North America; administrative support was provided by the ASN. This research was supported in part by the Intramural Research Program of the NIH, National Institute of Diabetes and Digestive and Kidney Diseases (KDH). NR 22 TC 117 Z9 119 U1 13 U2 52 PU AMER SOC NUTRITION-ASN PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0002-9165 J9 AM J CLIN NUTR JI Am. J. Clin. Nutr. PD APR PY 2012 VL 95 IS 4 BP 989 EP 994 DI 10.3945/ajcn.112.036350 PG 6 WC Nutrition & Dietetics SC Nutrition & Dietetics GA 033KQ UT WOS:000310795300001 PM 22434603 ER PT J AU Masuda, T Tsuda, M Yoshinaga, R Tozaki-Saitoh, H Ozato, K Tamura, T Inoue, K AF Masuda, Takahiro Tsuda, Makoto Yoshinaga, Ryohei Tozaki-Saitoh, Hidetoshi Ozato, Keiko Tamura, Tomohiko Inoue, Kazuhide TI IRF8 Is a Critical Transcription Factor for Transforming Microglia into a Reactive Phenotype SO CELL REPORTS LA English DT Article ID SEQUENCE BINDING-PROTEIN; CENTRAL-NERVOUS-SYSTEM; NEUROPATHIC PAIN; SPINAL MICROGLIA; RECEPTORS; MACROPHAGES; EXPRESSION; BRAIN; CELLS; ACTIVATION AB Microglia become activated by multiple types of damage in the nervous system and play essential roles in neuronal pathologies. However, how microglia transform into reactive phenotypes is poorly understood. Here, we identify the transcription factor interferon regulatory factor 8 (IRF8) as a critical regulator of reactive microglia. Within the spinal cord, IRF8 expression was normally low; however, the expression was markedly upregulated in microglia, but not in neurons or astrocytes, after peripheral nerve injury (PNI). IRF8 overexpression in cultured microglia promoted the transcription of genes associated with reactive states; conversely, IRF8 deficiency prevented these gene expressions in the spinal cord following PNI. Furthermore, IRF8-deficient mice were resistant to neuropathic pain, a common sequela of PNI, and transferring IRF8-overexpressing microglia spinally to normal mice produced pain. Therefore, IRF8 may activate a program of gene expression that transforms microglia into a reactive phenotype. Our findings provide a newly observed mechanism for microglial activation. C1 [Masuda, Takahiro; Tsuda, Makoto; Yoshinaga, Ryohei; Tozaki-Saitoh, Hidetoshi; Inoue, Kazuhide] Kyushu Univ, Grad Sch Pharmaceut Sci, Dept Mol & Syst Pharmacol, Higashi Ku, Fukuoka 8128582, Japan. [Ozato, Keiko] NICHHD, Program Genom Differentiat, NIH, Bethesda, MD 20892 USA. [Tamura, Tomohiko] Yokohama City Univ, Grad Sch Med, Dept Immunol, Yokohama, Kanagawa 2360004, Japan. RP Tsuda, M (reprint author), Kyushu Univ, Grad Sch Pharmaceut Sci, Dept Mol & Syst Pharmacol, Higashi Ku, 3-1-1 Maidashi, Fukuoka 8128582, Japan. EM tsuda@phar.kyushu-u.ac.jp; inoue@phar.kyushu-u.ac.jp RI U-ID, Kyushu/C-5291-2016 FU JSPS through NEXT Program; MEXT of Japan; Core-to-Core program of JSPS FX This work was supported by grants from the JSPS through the NEXT Program initiated by the CSTP (M. T.) and the MEXT of Japan (T. M., M. T., K. I.) and from the Core-to-Core program of JSPS (K. I.). We thank Ms. Junko Kitano, Ms. Yukari Hasegawa, Dr. Shigeo Hasegawa and the Research Support Center (Graduate School of Medical Sciences, Kyushu University) for assisting with experiments, and Dr. Hiroyuki Miyoshi (RIKEN BioResource Center) for providing the lentiviral vector and its packaging plasmids. T. M. designed and performed most of the experiments, analyzed the data, and wrote the manuscript. M. T. conceived the study, supervised the overall project, performed immunohistochemical experiments, and wrote the manuscript. R.Y. assisted with the experiments. H.T.-S. optimized transduction of lentiviral vectors into primary cultured microglia. K.O. and T. T. provided critical materials including Irf8-/- mice and advice on data interpretation. K. I. supervised the overall project and wrote the manuscript. NR 25 TC 65 Z9 68 U1 0 U2 5 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 2211-1247 J9 CELL REPORTS JI Cell Reports PD APR PY 2012 VL 1 IS 4 BP 334 EP 340 DI 10.1016/j.celrep.2012.02.014 PG 7 WC Cell Biology SC Cell Biology GA 019BN UT WOS:000309712000006 PM 22832225 ER PT J AU Sacks, DB Arnold, M Bakris, GL Bruns, DE Horvath, AR Kirkman, MS Lemmark, A Metzger, BE Nathan, DM AF Sacks, David B. Arnold, Mark Bakris, George L. Bruns, David E. Horvath, Andrea Rita Kirkman, M. Sue Lemmark, Ake Metzger, Boyd E. Nathan, David M. TI Practice Guides of the Clinical Laboratory Guides and recommendations for the diagnosis and treatment of Diabetes Mellitus Chapters 1-6 SO ACTA BIOQUIMICA CLINICA LATINOAMERICANA LA Spanish DT Article ID IMPAIRED FASTING GLUCOSE; NUTRITION EXAMINATION SURVEY; COST-EFFECTIVENESS ANALYSIS; NEAR-INFRARED SPECTROSCOPY; LONG-TERM COMPLICATIONS; CRITICALLY-ILL PATIENTS; PATHOLOGISTS Q-PROBES; BLOOD-GLUCOSE; PLASMA-GLUCOSE; QUALITY SPECIFICATIONS C1 [Sacks, David B.] NIH, Dept Lab Med, Bethesda, MD 20892 USA. [Arnold, Mark] Univ Iowa, Dept Chem, Iowa City, IA 52242 USA. [Bakris, George L.] Univ Chicago, Dept Med, Hypertens Dis Unit, Sect Endocrinol Diabet & Metab, Chicago, IL 60637 USA. [Bruns, David E.] Univ Virginia, Sch Med, Dept Pathol, Charlottesville, VA 22908 USA. [Horvath, Andrea Rita] Univ Sydney, Screening & Test Evaluat Program, Sch Publ Hlth, SEALS Dept Clin Chem,Prince Wales Hosp, Sydney, NSW 2006, Australia. [Kirkman, M. Sue] Amer Diabet Assoc, Alexandria, VA USA. [Lemmark, Ake] Lund Univ, Dept Clin Sci, CRC, Skane Univ Hosp Malmo, Malmo, Sweden. [Metzger, Boyd E.] Northwestern Univ, Div Endocrinol, Feinberg Sch Med, Chicago, IL 60611 USA. [Nathan, David M.] Univ Toronto, Toronto, ON M5S 1A1, Canada. [Nathan, David M.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Nathan, David M.] Harvard Univ, Sch Med, Ctr Diabet, Boston, MA USA. RP Sacks, DB (reprint author), NIH, Dept Lab Med, Bldg 10, Bethesda, MD 20892 USA. NR 191 TC 0 Z9 0 U1 0 U2 2 PU FEDERACION BIOQUIMICA PROVINCIA BUENOS AIRES PI LA PLATA, BUENOS AIRES PA CALLE 6, NO. 1344, 1900 LA PLATA, BUENOS AIRES, ARGENTINA SN 0325-2957 EI 1851-6114 J9 ACTA BIOQUIM CLIN L JI Acta Bioquim. Clin. Latinoam. PD APR-JUN PY 2012 VL 46 IS 2 BP 303 EP 336 PG 34 WC Medical Laboratory Technology SC Medical Laboratory Technology GA 015DR UT WOS:000309426200014 ER PT J AU Klionsky, DJ Abdalla, FC Abeliovich, H Abraham, RT Acevedo-Arozena, A Adeli, K Agholme, L Agnello, M Agostinis, P Aguirre-Ghiso, JA Ahn, HJ Ait-Mohamed, O Ait-Si-Ali, S Akematsu, T Akira, S Al-Younes, HM Al-Zeer, MA Albert, ML Albin, RL Alegre-Abarrategui, J Aleo, MF Alirezaei, M Almasan, A Almonte-Becerril, M Amano, A Amaravadi, R Amarnath, S Amer, AO Andrieu-Abadie, N Anantharam, V Ann, DK Anoopkumar-Dukie, S Aoki, H Apostolova, N Arancia, G Aris, JP Asanuma, K Asare, NYO Ashida, H Askanas, V Askew, DS Auberger, P Baba, M Backues, SK Baehrecke, EH Bahr, BA Bai, XY Bailly, Y Baiocchi, R Baldini, G Balduini, W Ballabio, A Bamber, BA Bampton, ETW Banhegyi, G Bartholomew, CR Bassham, DC Bast, RC Batoko, H Bay, BH Beau, I Bechet, DM Begley, TJ Behl, C Behrends, C Bekri, S Bellaire, B Bendall, LJ Benetti, L Berliocchi, L Bernardi, H Bernassola, F Besteiro, S Bhatia-Kissova, I Bi, XN Biard-Piechaczyk, M Blum, JS Boise, LH Bonaldo, P Boone, DL Bornhauser, BC Bortoluci, KR Bossis, I Bost, F Bourquin, JP Boya, P Boyer-Guittaut, M Bozhkov, PV Brady, NR Brancolini, C Brech, A Brenman, JE Brennand, A Bresnick, EH Brest, P Bridges, D Bristol, ML Brookes, PS Brown, EJ Brumell, JH Brunetti-Pierri, N Brunk, UT Bulman, DE Bultman, SJ Bultynck, G Burbulla, LF Bursch, W Butchar, JP Buzgariu, W Bydlowski, SP Cadwell, K Cahova, M Cai, DS Cai, JY Cai, Q Calabretta, B Calvo-Garrido, J Camougrand, N Campanella, M Campos-Salinas, J Candi, E Cao, LZ Caplan, AB Carding, SR Cardoso, SM Carew, JS Carlin, CR Carmignac, V Carneiro, LAM Carra, S Caruso, RA Casari, G Casas, C Castino, R Cebollero, E Cecconi, F Celli, J Chaachouay, H Chae, HJ Chai, CY Chan, DC Chan, EY Chang, RCC Che, CM Chen, CC Chen, GC Chen, GQ Chen, M Chen, Q Chen, SSL Chen, WL Chen, X Chen, XM Chen, XQ Chen, YG Chen, YY Chen, YQ Chen, YJ Chen, ZX Cheng, A Cheng, CHK Cheng, Y Cheong, H Cheong, JH Cherry, S Chess-Williams, R Cheung, ZH Chevet, E Chiang, HL Chiarelli, R Chiba, T Chin, LS Chiou, SH Chisari, FV Cho, CH Cho, DH Choi, AMK Choi, D Choi, KS Choi, ME Chouaib, S Choubey, D Choubey, V Chu, CT Chuang, TH Chueh, SH Chun, T Chwae, YJ Chye, ML Ciarcia, R Ciriolo, MR Clague, MJ Clark, RSB Clarke, PGH Clarke, R Codogno, P Coller, HA Colombo, MI Comincini, S Condello, M Condorelli, F Cookson, MR Coppens, GHCI Corbalan, R Cossart, P Costelli, P Costes, S Coto-Montes, A Couve, E Coxon, FP Cregg, JM Crespo, JL Cronje, MJ Cuervo, AM Cullen, JJ Czaja, MJ D'Amelio, M Darfeuille-Michaud, A Davids, LM Davies, FE De Felici, M de Groot, JF de Haan, CAM De Martino, L De Milito, A De Tata, V Debnath, J Degterev, A Dehay, B Delbridge, LMD Demarchi, F Deng, YZ Dengjel, J Dent, P Denton, D Deretic, V Desai, SD Devenish, RJ Di Gioacchino, M Di Paolo, G Di Pietro, C Diaz-Araya, G Diaz-Laviada, I Diaz-Meco, MT Diaz-Nido, J Dikic, I Dinesh-Kumar, SP Ding, WX Distelhorst, CW Diwan, A Djavaheri-Mergny, M Dokudovskaya, S Dong, Z Dorsey, FC Dosenko, V Dowling, JJ Doxsey, S Dreux, M Drew, ME Duan, QH Duchosal, MA Duff, K Dugail, I Durbeej, M Duszenko, M Edelstein, CL Edinger, AL Egea, G Eichinger, L Eissa, NT Ekmekcioglu, S El-Deiry, WS Elazar, Z Elgendy, M Ellerby, LM Eng, KE Engelbrecht, AM Engelender, S Erenpreisa, J Escalante, R Esclatine, A Eskelinen, EL Espert, L Espina, V Fan, HZ Fan, J Fan, QW Fan, Z Fang, SY Fang, YQ Fanto, M Fanzani, A Farkas, T Farre, JC Faure, M Fechheimer, M Feng, CG Feng, J Feng, QL Feng, YJ Fesus, L Feuer, R Figueiredo-Pereira, ME Fimia, GM Fingar, DC Finkbeiner, S Finkel, T Finley, KD Fiorito, F Fisher, EA Fisher, PB Flajolet, M Florez-McClure, ML Florio, S Fon, EA Fornai, F Fortunato, F Fotedar, R Fowler, DH Fox, HS Franco, R Frankel, LB Fransen, M Fuentes, JM Fueyo, J Fujii, J Fujisaki, K Fujita, E Fukuda, M Furukawa, RH Gaestel, M Gailly, P Gajewska, M Galliot, B Galy, V Ganesh, S Ganetzky, B Ganley, IG Gao, FB Gao, GF Gao, JM Garcia, L Garcia-Manero, G Garcia-Marcos, M Garmyn, M Gartel, AL Gatti, E Gautel, M Gawriluk, TR Gegg, ME Geng, JF Germain, M Gestwicki, JE Gewirtz, DA Ghavami, S Ghosh, P Giammarioli, AM Giatromanolaki, AN Gibson, SB Gilkerson, RW Ginger, ML Ginsberg, HN Golab, J Goligorsky, MS Golstein, P Gomez-Manzano, C Goncu, E Gongora, C Gonzalez, CD Gonzalez, R Gonzalez-Estevez, C Gonzalez-Polo, RA Gonzalez-Rey, E Gorbunov, NV Gorski, S Goruppi, S Gottlieb, RA Gozuacik, D Granato, GE Grant, GD Green, KN Gregorc, A Gros, F Grose, C Grunt, TW Gual, P Guan, JL Guan, KL Guichard, SM Gukovskaya, AS Gukovsky, I Gunst, J Gustafsson, AB Halayko, AJ Hale, AN Halonen, SK Hamasaki, M Han, F Han, T Hancock, MK Hansen, M Harada, H Harada, M Hardt, SE Harper, JW Harris, AL Harris, J Harris, SD Hashimoto, M Haspel, JA Hayashi, S Hazelhurst, LA He, CC He, YW Hebert, MJ Heidenreich, KA Helfrich, MH Helgason, GV Henske, EP Herman, B Herman, PK Hetz, C Hilfiker, S Hill, JA Hocking, LJ Hofman, P Hofmann, TG Hohfeld, J Holyoake, TL Hong, MH Hood, DA Hotamisligil, GS Houwerzijl, EJ Hoyer-Hansen, M Hu, BR Hu, CAA Hu, HM Hua, Y Huang, CH Huang, J Huang, SB Huang, WP Huber, TB Huh, WK Hung, TH Hupp, TR Hur, GM Hurley, JB Hussain, SNA Hussey, PJ Hwang, JJ Hwang, SM Ichihara, A Ilkhanizadeh, S Inoki, K Into, T Iovane, V Iovanna, JL Ip, NY Isaka, Y Ishida, H Isidoro, C Isobe, K Iwasaki, A Izquierdo, M Izumi, Y Jaakkola, PM Jaattela, M Jackson, GR Jackson, WT Janji, B Jendrach, M Jeon, JH Jeung, EB Jiang, H Jiang, HC Jiang, JX Jiang, M Jiang, Q Jiang, XJ Jiang, XJ Jimenez, A Jin, MY Jin, SK Joe, CO Johansen, T Johnson, DE Johnson, GVW Jones, NL Joseph, B Joseph, SK Joubert, AM Juhasz, G Juillerat-Jeanneret, L Jung, CH Jung, YK Kaarniranta, K Kaasik, A Kabuta, T Kadowaki, M Kagedal, K Kamada, Y Kaminskyy, VO Kampinga, HH Kanamori, H Kang, C Kang, KB Kang, KI Kang, R Kang, YA Kanki, T Kanneganti, TD Kanno, H Kanthasamy, AG Kanthasamy, A Karantza, V Kaushal, GP Kaushik, S Kawazoe, Y Ke, PY Kehrl, JH Kelekar, A Kerkhoff, C Kessel, DH Khalil, H Kiel, JAKW Kiger, AA Kihara, A Kim, DR Kim, DH Kim, DH Kim, EK Kim, HR Kim, JS Kim, JH Kim, JC Kim, JK Kim, PK Kim, SW Kim, YS Kim, Y Kimchi, A Kimmelman, AC King, JS Kinsella, TJ Kirkin, V Kirshenbaum, LA Kitamoto, K Kitazato, K Klein, L Klimecki, WT Klucken, J Knecht, E Ko, BCB Koch, JC Koga, H Koh, JY Koh, YH Koike, M Komatsu, M Kominami, E Kong, HJ Kong, WJ Korolchuk, VI Kotake, Y Koukourakis, MI Flores, JBK Kovacs, AL Kraft, C Krainc, D Kraemer, H Kretz-Remy, C Krichevsky, AM Kroemer, G Krueger, R Krut, O Ktistakis, NT Kuan, CY Kucharczyk, R Kumar, A Kumar, R Kumar, S Kundu, M Kung, HJ Kurz, T Kwon, HJ La Spada, AR Lafont, F Lamark, T Landry, J Lane, JD Lapaquette, P Laporte, JF Laszlo, L Lavandero, S Lavoie, JN Layfield, R Lazo, PA Le, WD Le Cam, L Ledbetter, DJ Lee, AJX Lee, BW Lee, GM Lee, J Lee, JH Lee, M Lee, MS Lee, SH Leeuwenburgh, C Legembre, P Legouis, R Lehmann, M Lei, HY Lei, QY Leib, DA Leiro, J Lemasters, JJ 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Xi, Zhijun Xia, Pu Xiao, Gengfu Xie, Zhiping Xie, Zhonglin Xu, Da-zhi Xu, Jianzhen Xu, Liang Xu, Xiaolei Yamamoto, Ai Yamamoto, Akitsugu Yamashina, Shunhei Yamashita, Michiaki Yan, Xianghua Yanagida, Mitsuhiro Yang, Dun-Sheng Yang, Elizabeth Yang, Jin-Ming Yang, Shi Yu Yang, Wannian Yang, Wei Yuan Yang, Zhifen Yao, Meng-Chao Yao, Tso-Pang Yeganeh, Behzad Yen, Wei-Lien Yin, Jia-jing Yin, Xiao-Ming Yoo, Ook-Joon Yoon, Gyesoon Yoon, Seung-Yong Yorimitsu, Tomohiro Yoshikawa, Yuko Yoshimori, Tamotsu Yoshimoto, Kohki You, Ho Jin Youle, Richard J. Younes, Anas Yu, Li Yu, Long Yu, Seong-Woon Yu, Wai Haung Yuan, Zhi-Min Yue, Zhenyu Yun, Cheol-Heui Yuzaki, Michisuke Zabirnyk, Olga Silva-Zacarin, Elaine Zacks, David Zacksenhaus, Eldad Zaffaroni, Nadia Zakeri, Zahra Zeh, Herbert J., III Zeitlin, Scott O. Zhang, Hong Zhang, Hui-Ling Zhang, Jianhua Zhang, Jing-Pu Zhang, Lin Zhang, Long Zhang, Ming-Yong Zhang, Xu Dong Zhao, Mantong Zhao, Yi-Fang Zhao, Ying Zhao, Zhizhuang J. Zheng, Xiaoxiang Zhivotovsky, Boris Zhong, Qing Zhou, Cong-Zhao Zhu, Changlian Zhu, Wei-Guo Zhu, Xiao-Feng Zhu, Xiongwei Zhu, Yuangang Zoladek, Teresa Zong, Wei-Xing Zorzano, Antonio Zschocke, Juergen Zuckerbraun, Brian TI Guidelines for the use and interpretation of assays for monitoring autophagy SO AUTOPHAGY LA English DT Review DE autolysosome; autophagosome; flux; LC3; lysosome; phagophore; stress; vacuole ID ACTIVATED PROTEIN-KINASE; CHAPERONE-MEDIATED AUTOPHAGY; PROGRAMMED CELL-DEATH; ISOLATED RAT HEPATOCYTES; STARVATION-INDUCED AUTOPHAGY; VACUOLE TARGETING PATHWAY; GLUCAGON-INDUCED AUTOPHAGY; BREAST-CANCER CELLS; BETAINE HOMOCYSTEINE METHYLTRANSFERASE; ENDOPLASMIC-RETICULUM STRESS AB In 2008 we published the first set of guidelines for standardizing research in autophagy. Since then, research on this topic has continued to accelerate, and many new scientists have entered the field. Our knowledge base and relevant new technologies have also been expanding. Accordingly, it is important to update these guidelines for monitoring autophagy in different organisms. Various reviews have described the range of assays that have been used for this purpose. Nevertheless, there continues to be confusion regarding acceptable methods to measure autophagy, especially in multicellular eukaryotes. A key point that needs to be emphasized is that there is a difference between measurements that monitor the numbers or volume of autophagic elements (e.g., autophagosomes or autolysosomes) at any stage of the autophagic process vs. those that measure flux through the autophagy pathway (i.e., the complete process); thus, a block in macroautophagy that results in autophagosome accumulation needs to be differentiated from stimuli that result in increased autophagic activity, defined as increased autophagy induction coupled with increased delivery to, and degradation within, lysosomes (in most higher eukaryotes and some protists such as Dictyostelium) or the vacuole (in plants and fungi). In other words, it is especially important that investigators new to the field understand that the appearance of more autophagosomes does not necessarily equate with more autophagy. In fact, in many cases, autophagosomes accumulate because of a block in trafficking to lysosomes without a concomitant change in autophagosome biogenesis, whereas an increase in autolysosomes may reflect a reduction in degradative activity. Here, we present a set of guidelines for the selection and interpretation of methods for use by investigators who aim to examine macroautophagy and related processes, as well as for reviewers who need to provide realistic and reasonable critiques of papers that are focused on these processes. These guidelines are not meant to be a formulaic set of rules, because the appropriate assays depend in part on the question being asked and the system being used. In addition, we emphasize that no individual assay is guaranteed to be the most appropriate one in every situation, and we strongly recommend the use of multiple assays to monitor autophagy. 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[Baehrecke, Eric H.] Univ Massachusetts, Sch Med, Dept Canc Biol, Worcester, MA USA. [Bahr, Ben A.] Univ N Carolina Pembroke, William C Friday Lab, Biotechnol Res & Training Ctr, Pembroke, NC USA. [Bai, Xue-Yuan; Chen, Xiangmei] Chinese Peoples Liberat Army Gen Hosp, State Key Lab Kidney Dis, Dept Nephrol, Beijing, Peoples R China. [Bailly, Yannick] Univ Strasbourg, INCI CNRS UPR 3212, Strasbourg, France. [Baiocchi, Robert] Ohio State Univ, Div Hematol, Columbus, OH 43210 USA. [Baldini, Giulia] Univ Arkansas Med Sci, Dept Biochem & Mol Biol, Little Rock, AR 72205 USA. [Balduini, Walter] Univ Urbino Carlo Bo, Dept Biomol Sci, Urbino, Italy. [Ballabio, Andrea; Brunetti-Pierri, Nicola; Settembre, Carmine] Telethon Inst Genet & Med TIGEM, Naples, Italy. [Ballabio, Andrea; Brunetti-Pierri, Nicola; Settembre, Carmine] Univ Naples Federico II, Dept Pediat, Naples, Italy. [Ballabio, Andrea; Settembre, Carmine] Baylor Coll Med, Jan & Dan Duncan Neurol Res Inst, Houston, TX 77030 USA. [Bamber, Bruce A.] Univ Toledo, Dept Biol Sci, Toledo, OH 43606 USA. [Bampton, Edward T. W.; Melino, Gerry] Univ Leicester, MRC, Toxicol Unit, Leicester, Leics, England. [Banhegyi, Gabor] Semmelweis Univ, Dept Med Chem Mol Biol & Pathobiochem, H-1085 Budapest, Hungary. [Bassham, Diane C.] Iowa State Univ, Dept Genet Dev & Cell Biol, Ames, IA USA. [Bast, Robert C., Jr.; Fan, Zhen; Lopez-Berestein, Gabriel; Lu, Zhen; Ozpolat, Bulent] Univ Texas MD Anderson Canc Ctr, Dept Expt Therapeut, Houston, TX 77030 USA. [Batoko, Henri] Catholic Univ Louvain, Inst Life Sci, UCL ISV, B-3000 Louvain, Belgium. [Bay, Boon-Huat] Natl Univ Singapore, Yong Loo Lin Sch Med, Dept Anat, Singapore 117595, Singapore. [Beau, Isabelle; Esclatine, Audrey] INSERM, UMR S984, Chatenay Malabry, France. [Beau, Isabelle; Esclatine, Audrey] Univ Paris 11, Chatenay Malabry, France. [Bechet, Daniel M.] INRA, UMR 1019, Unite Nutr Humaine, Clermont Ferrand, France. 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[Bernassola, Francesca; Marfe, Gabriella; Palumbo, Camilla] Univ Roma Tor Vergata, Dept Expt Med & Biochem Sci, Rome, Italy. [Besteiro, Sebastien] Univ Montpellier 2, CNRS, DIMNP, UMR5235, Montpellier, France. [Bhatia-Kissova, Ingrid] Comenius Univ, Dept Biochem, Bratislava, Slovakia. [Bi, Xiaoning] Western Univ Hlth Sci, Pomona, CA USA. [Biard-Piechaczyk, Martine; Espert, Lucile] CNRS, Ctr Etud Agents Pathogenes & Biotechnol Sante, UM1, UM2, Montpellier, France. [Blum, Janice S.] Indiana Univ, Sch Med, Dept Microbiol & Immunol, Indianapolis, IN 46202 USA. [Boise, Lawrence H.; Lonial, Sagar; Sun, Shi-Yong] Emory Univ, Sch Med, Winship Canc Inst, Dept Hematol & Med Oncol, Atlanta, GA USA. [Bonaldo, Paolo; Sandri, Marco] Univ Padua, Dept Biomed Sci, Padua, Italy. [Boone, David L.] Univ Chicago, Dept Med, Chicago, IL 60637 USA. [Bornhauser, Beat C.; Bourquin, Jean-Pierre] Univ Zurich, Univ Childrens Hosp, Dept Oncol, Zurich, Switzerland. [Bortoluci, Karina R.] Univ Fed Sao Paulo, Dept Biol Sci, Sao Paulo, Brazil. [Bortoluci, Karina R.] Univ Fed Sao Paulo, Cellular & Mol Therapy Ctr, Sao Paulo, Brazil. [Begley, Thomas J.] Univ Maryland, Dept Vet Med, College Pk, MD 20742 USA. [Boya, Patricia] CSIC, CIB, Ctr Invest Biol, Dept Cell Proliferat & Dev, Madrid, Spain. [Boyer-Guittaut, Michael] Univ Franche Comte, Biochim Lab, EA3922, UFR Sci & Tech,IFR133, F-25030 Besancon, France. [Bozhkov, Peter V.] Swedish Univ Agr Sci, Uppsala BioCtr, Dept Plant Biol & Forest Genet, Uppsala, Sweden. [Brady, Nathan R.] Heidelberg Univ, German Canc Res Ctr DKFZ, Heidelberg, Germany. [Brady, Nathan R.] Heidelberg Univ, Fac Med, Heidelberg, Germany. [Brancolini, Claudio] Univ Udine, Dipartment Sci Med & Biol, I-33100 Udine, Italy. [Brech, Andreas; Nezis, Ioannis P.; Rusten, Tor Erik; Stenmark, Harald] Univ Oslo, Ctr Canc Biomed, Oslo, Norway. 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[Burbulla, Lena F.] Univ Tubingen, Hertie Inst Clin Brain Res, Dept Neurodegenerat Dis, Tubingen, Germany. [Burbulla, Lena F.] DZNE, German Ctr Neurodegenerat Dis, Tubingen, Germany. [Bursch, Wilfried] Med Univ Vienna, Inst Canc Res, Div Oncol, Dept Med 1, Vienna, Austria. [Butchar, Jonathan P.] Ohio State Univ, Dept Internal Med, Div Pulm Allergy Crit Care & Sleep Med, Columbus, OH 43210 USA. [Buzgariu, Wanda; Galliot, Brigitte] Univ Geneva, Dept Genet & Evolut, Geneva, Switzerland. [Bydlowski, Sergio P.] Univ Sao Paulo, Sch Med, Lab Genet & Mol Hematol, Sao Paulo, Brazil. [Cadwell, Ken] NYU, Sch Med, Dept Microbiol, Skirball Inst Biomol Med, New York, NY 10016 USA. [Cahova, Monika; Papackova, Zuzana] Inst Clin & Expt Med, Dept Metab & Diabet, Prague, Czech Republic. [Cai, Dongsheng] Albert Einstein Coll Med, Dept Mol Pharmacol, Bronx, NY 10467 USA. [Cai, Jiyang] Vanderbilt Univ, Vanderbilt Eye Inst, Nashville, TN USA. 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[Candi, Eleonora] Univ Roma Tor Vergata, Dept Biochem, Rome, Italy. [Cao, Lizhi] Cent S Univ, Xiangya Hosp, Dept Pediat, Changsha, Hunan, Peoples R China. [Caplan, Allan B.] Univ Idaho, Dept Plant Soil & Entomol Sci, Moscow, ID 83843 USA. [Carding, Simon R.] Univ E Anglia, Fac Hlth, Norwich Sch Med, GI Tract Programme,Inst Food Res, Norwich NR4 7TJ, Norfolk, England. [Carding, Simon R.] Univ E Anglia, Fac Hlth, Norwich Sch Med, Dept Mucosal Immunol, Norwich NR4 7TJ, Norfolk, England. [Cardoso, Sandra M.; Moreira, Paula I.] Univ Coimbra, Fac Med, Coimbra, Portugal. [Cardoso, Sandra M.; Moreira, Paula I.] Univ Coimbra, Ctr Neurosci & Cell Biol, Coimbra, Portugal. [Carew, Jennifer S.; Nawrocki, Steffan T.] Univ Texas Hlth Sci Ctr San Antonio, Dept Med, Div Hematol Oncol, San Antonio, TX 78229 USA. [Carlin, Cathleen R.] Case Western Reserve Univ, Dept Mol Biol & Microbiol, Cleveland, OH 44106 USA. 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[Cebollero, Eduardo] Univ Med Ctr Utrecht, Dept Biochem & Cell Biol, Utrecht, Netherlands. [Cecconi, Francesco] IRCCS Santa Lucia Fdn, Rome, Italy. [Cecconi, Francesco; Ciriolo, Maria R.; Piacentini, Mauro] Univ Roma Tor Vergata, Dept Biol, Dulbecco Telethon Inst, I-00173 Rome, Italy. [Celli, Jean] NIAID, Intracellular Parasites Lab, Rocky Mt Labs, NIH, Hamilton, MT USA. [Chaachouay, Hassan; Rodemann, H. Peter] Univ Tubingen, Dept Radiat Oncol, Div Radiat Biol & Mol Environm Res, Tubingen, Germany. [Chae, Han-Jung] Chonbuk Univ, Sch Med, Cardiovasc Res Inst, Chonbuk, South Korea. [Chae, Han-Jung] Chonbuk Univ, Dept Pharmacol, Chonbuk, South Korea. [Chai, Chee-Yin] Kaohsiung Med Univ Hosp, Dept Pathol, Kaohsiung, Taiwan. [Chan, David C.] CALTECH, Div Biol, Pasadena, CA 91125 USA. [Chan, Edmond Y.; Coppens, Graham H. Coombs Isabelle] Univ Strathclyde, Strathclyde Inst Pharm & Biomed Sci, Glasgow, Lanark, Scotland. [Chang, Raymond Chuen-Chung] Univ Hong Kong, Li Ka Shing Fac Med, Dept Anat, Lab Neurodegenerat Dis, Hong Kong, Hong Kong, Peoples R China. [Che, Chi-Ming; Lok, Chun-Nam; Sy, Lai-King] Univ Hong Kong, Dept Chem, Hong Kong, Hong Kong, Peoples R China. [Chen, Ching-Chow; Lin, Wan-Wan] Natl Taiwan Univ, Coll Med, Dept Pharmacol, Taipei 10764, Taiwan. [Chen, Guang-Chao; Yang, Wei Yuan] Acad Sinica, Inst Biol Chem, Taipei, Taiwan. [Chen, Guo-Qiang] Shanghai Jiao Tong Univ, Sch Med, Key Lab Cell Differentiat & Apoptosis, Chinese Minist Educ, Shanghai 200030, Peoples R China. [Chen, Min; Wang, Jin] Baylor Coll Med, Dept Pathol & Immunol, Houston, TX 77030 USA. [Chen, Quan] Chinese Acad Sci, Inst Zool, State Key Lab Membrane Biol, Beijing, Peoples R China. [Chen, Quan] Nankai Univ, Coll Life Sci, Tianjin 300071, Peoples R China. [Chen, Steve S. -L.; Ke, Po-Yuan; Lin, Yi-Ling] Acad Sinica, Inst Biomed Sci, Taipei, Taiwan. [Chen, WenLi] S China Normal Univ, MOE Key Lab Laser Life Sci, Guangzhou, Guangdong, Peoples R China. [Chen, WenLi] S China Normal Univ, Inst Laser Life Sci, Guangzhou, Guangdong, Peoples R China. [Chen, Xi] Zhejiang Univ, Sch Med, Childrens Hosp, Hangzhou 310003, Zhejiang, Peoples R China. [Chen, Xiequn] Fourth Mil Med Univ, Xijing Hosp, Dept Hematol, Xian 710032, Peoples R China. [Chen, Ye-Guang; Liu, Yule; Yu, Li] Tsinghua Univ, Sch Life Sci, Beijing 100084, Peoples R China. [Chen, Yingyu] Peking Univ, Dept Immunol, Ctr Human Dis Genom, Beijing 100871, Peoples R China. [Chen, Yongqiang; Guan, Jun-Lin; Towns, Roberto; Wiley, John W.] Univ Michigan, Sch Med, Dept Internal Med, Ann Arbor, MI USA. [Chen, Yu-Jen] Mackay Mem Hosp, Dept Radiat Oncol, Taipei, Taiwan. [Chen, Zhixiang] Purdue Univ, Dept Bot & Plant Pathol, W Lafayette, IN 47907 USA. [Cheng, Alan] Univ Louisville, Dept Biochem & Mol Biol, Louisville, KY 40292 USA. [Cheng, Christopher H. K.] Chinese Univ Hong Kong, Sch Biomed Sci, Shatin, Hong Kong, Peoples R China. [Cheng, Yan; Wang, Hong-Gang; Yang, Jin-Ming] Penn State Univ, Coll Med, Penn State Hershey Canc Inst, Dept Pharmacol, Hershey, PA USA. [Cheong, Heesun; Thompson, Craig B.] Mem Sloan Kettering Canc Ctr, Dept Canc Biol & Genet, New York, NY 10021 USA. [Cheong, Jae-Ho] Yonsei Univ, Coll Med, Dept Surg, Seoul, South Korea. [Cherry, Sara] Univ Penn, Dept Microbiol, Philadelphia, PA 19104 USA. [Chess-Williams, Russ] Bond Univ, Fac Hlth Sci & Med, Southport, Qld 4229, Australia. [Cheung, Zelda H.] Univ Hong Kong, Li Ka Shing Fac Med, Dept Biochem, Hong Kong, Hong Kong, Peoples R China. [Chevet, Eric] Univ Bordeaux Segalen, Bordeaux, France. [Chevet, Eric] INSERM, U1053, Bordeaux, France. [Chiang, Hui-Ling] Penn State Univ, Coll Med, Dept Cellular & Mol Physiol, Hershey, PA USA. [Chiba, Tomoki] Univ Tsukuba, Grad Sch Life & Environm Sci, Ibaraki, Japan. [Chin, Lih-Shen; Li, Lian; Mao, Zixu] Emory Univ, Sch Med, Dept Pharmacol, Atlanta, GA 30322 USA. [Chiou, Shih-Hwa] Natl Yang Ming Univ, Sch Med, Inst Pharmacol, Taipei 112, Taiwan. [Cho, Chi Hin] Chinese Univ Hong Kong, Sch Biomed Sci, Hong Kong, Hong Kong, Peoples R China. [Cho, Dong-Hyung] Kyung Hee Univ, Grad Sch EW Med Sci, Yongin, South Korea. [Choi, Augustine M. K.; Haspel, Jeffrey A.; Henske, Elizabeth P.; Nakahira, Kiichi; Ryter, Stefan W.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Div Pulm & Crit Care Med, Boston, MA 02115 USA. [Choi, DooSeok] Sungkyunkwan Univ, Sch Med, Samsung Med Ctr, Dept Obstet & Gynecol, Seoul, South Korea. [Choi, Kyeong Sook] Ajou Univ, Sch Med, Inst Med Sci, Suwon 441749, South Korea. [Choi, Mary E.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Med,Renal Div, Boston, MA 02115 USA. [Chouaib, Salem] Inst Gustave Roussy, INSERM, U753 PR1, F-94805 Villejuif, France. [Choubey, Divaker] Univ Cincinnati, Dept Environm Hlth, Cincinnati, OH USA. [Choubey, Vinay; Kaasik, Allen] Univ Tartu, Dept Pharmacol, EE-50090 Tartu, Estonia. [Chu, Charleen T.; Rabinowich, Hannah] Univ Pittsburgh, Sch Med, Dept Pathol, Pittsburgh, PA USA. [Chu, Charleen T.] Univ Pittsburgh, Sch Med, Ctr Neurosci, Pittsburgh, PA USA. [Chuang, Tsung-Hsien] Natl Hlth Res Inst, Immunol Res Ctr, Miaoli Cty, Taiwan. [Chueh, Sheau-Huei] Natl Def Med Ctr, Dept Biochem, Taipei, Taiwan. [Chun, Taehoon; Park, Ohkmae K.] Korea Univ, Sch Life Sci & Biotechnol, Seoul, South Korea. [Chwae, Yong-Joon] Ajou Univ, Sch Med, Dept Microbiol, Suwon 441749, South Korea. [Chye, Mee-Len] Univ Hong Kong, Sch Biol Sci, Pokfulam, Hong Kong, Peoples R China. [Ciarcia, Roberto; Florio, Salvatore; Granato, Giovanna Elvira] Univ Naples Federico II, Dept Struct Funct & Biol Technol, Naples, Italy. [Ciriolo, Maria R.] IRCCS San Raffaele, Rome, Italy. [Clague, Michael J.] Univ Liverpool, Physiol Lab, Inst Translat Med, Liverpool L69 3BX, Merseyside, England. [Clark, Robert S. B.] Safar Ctr Resuscitat Res, Pittsburgh, PA USA. [Clarke, Peter G. H.; Puyal, Julien] Univ Lausanne, Dept Biol Cellulaire & Morphol, Lausanne, Switzerland. [Clarke, Robert; Saha, Tapas] Georgetown Univ, Lombardi Comprehens Canc Ctr, Dept Oncol, Washington, DC USA. [Codogno, Patrice] Univ Paris S, INSERM, U984, Paris, France. [Coller, Hilary A.] Princeton Univ, Dept Mol Biol, Princeton, NJ 08544 USA. [Colombo, Maria I.] Univ Nacl Cuyo, CONICET, Inst Histol & Embriol, Lab Biol Celular & Mol, RA-5500 Mendoza, Argentina. [Comincini, Sergio] Univ Pavia, Dept Genet & Microbiol, I-27100 Pavia, Italy. [Condorelli, Fabrizio] Univ Piemonte Orientale, Fac Pharm, Novara, Italy. [Cookson, Mark R.] NIA, Cell Biol & Gene Express Sect, NIH, Bethesda, MD 20892 USA. [Corbalan, Ramon] Johns Hopkins Univ, Dept Mol Microbiol & Immunol, Baltimore, MD USA. [Cossart, Pascale] Pontificia Univ Catolica Chile, Fac Med, Dept Enfermedades Cardiovasc, Santiago, Chile. [Costelli, Paola] Inst Pasteur, Unite Interact Bacteries Cellules, Paris, France. [Costelli, Paola] INSERM, INRA, U604, USC2020, Paris, France. [Costes, Safia] Univ Turin, Dept Expt Med & Oncol, Turin, Italy. [Coto-Montes, Ana] Univ Calif Los Angeles, David Geffen Sch Med, Larry Hillblom Islet Res Ctr, Los Angeles, CA 90095 USA. [Couve, Eduardo] Univ Oviedo, Dept Morfol & Biol Celular, Oviedo, Spain. [Coxon, Fraser P.] Univ Valparaiso, Fac Ciencias, Dept Biol & Cs Ambientales, Valparaiso, Chile. [Cregg, James M.; Helfrich, Miep H.; Hocking, Lynne J.] Univ Aberdeen, Div Appl Med, Aberdeen, Scotland. [Crespo, Jose L.] Keck Grad Inst Appl Sci, Claremont, CA USA. [Cronje, Marianne J.] Univ Seville, CSIC, Inst Bioquim Vegetal Fotosintesis, Seville, Spain. Univ Johannesburg, Dept Biochem, Johannesburg, South Africa. [Kaushik, Susmita] Albert Einstein Coll Med, Dept Anat & Struct Biol, Bronx, NY 10467 USA. [Kaushik, Susmita; Koga, Hiroshi] Albert Einstein Coll Med, Dept Dev & Mol Biol, Bronx, NY 10467 USA. [D'Amelio, Marcello; Kaushik, Susmita; Koga, Hiroshi] Albert Einstein Coll Med, Marion Bessin Liver Res Ctr, Bronx, NY 10467 USA. Univ Iowa, Dept Surg, Iowa City, IA 52242 USA. [D'Amelio, Marcello] Albert Einstein Coll Med, Dept Med, Bronx, NY 10467 USA. Santa Lucia Fdn, European Ctr Brain Res, Expt Neurol Unit, Rome, Italy. Univ Campus Biomed, Rome, Italy. [Cuervo, Ana Maria; Darfeuille-Michaud, Arlette] INRA, USC 2018, Clermont Ferrand, France. [Cuervo, Ana Maria; Darfeuille-Michaud, Arlette] Univ Auvergne, INSERM, UMR 1071, Clermont Ferrand, France. [Cullen, Joseph J.; Davids, Lester M.] Univ Cape Town, Dept Human Biol, ZA-7925 Cape Town, South Africa. [Czaja, Mark J.; Davies, Faith E.] Inst Canc Res, Div Mol Pathol, Sutton, Surrey, England. [Czaja, Mark J.; Davies, Faith E.] Royal Marsden Hosp, Sutton, Surrey, England. [De Felici, Massimo] Univ Roma Tor Vergata, Dept Publ Hlth & Cell Biol, Rome, Italy. [de Groot, John F.; Fueyo, Juan; Gomez-Manzano, Candelaria; Jiang, Hong] Univ Texas Houston, MD Anderson Canc Ctr, Dept Neurooncol, Houston, TX 77030 USA. [de Haan, Cornelis A. M.; Monastyrska, Iryna] Univ Utrecht, Dept Infect Dis & Immunol, Div Virol, Utrecht, Netherlands. [De Martino, Luisa; Fiorito, Filomena; Iovane, Valentine; Pagnini, Ugo] Univ Naples Federico II, Dept Pathol & Anim Hlth, Naples, Italy. [De Milito, Angelo; Joseph, Bertrand; Panaretakis, Theocharis] Karolinska Inst, Dept Oncol Pathol, Canc Ctr Karolinska, Stockholm, Sweden. [De Tata, Vincenzo] Univ Pisa, Sch Med, Dept Expt Pathol, I-56100 Pisa, Italy. [Debnath, Jayanta] Univ Calif San Francisco, Dept Pathol, San Francisco, CA 94140 USA. [Degterev, Alexei] Tufts Univ, Sch Med, Dept Biochem, Boston, MA 02111 USA. [Dehay, Benjamin] Univ Bordeaux Segalen, Inst Malad Neurodegenerat, CNRS, UMR 5293, Bordeaux, France. [Delbridge, Lea M. D.] Univ Melbourne, Dept Physiol, Parkville, Vic 3052, Australia. [Demarchi, Francesca; Schneider, Claudio] Lab Nazl Consorzio Interuniv, Trieste, Italy. [Deng, Yi Zhen; Naqvi, Naweed I.] Natl Univ Singapore, Temasek Life Sci Lab, Fungal Pathobiol Grp, Singapore 117548, Singapore. [Dengjel, Joen] Freiburg Inst Adv Studies FRIAS, Sch Life Sci LifeNet, Freiburg, Germany. [Dent, Paul] Virginia Commonwealth Univ, Sch Med, VCU Massey Canc Ctr, Dept Neurosurg,VCU Inst Moleular Med, Richmond, VA USA. [Denton, Donna] SA Pathol, Ctr Canc Biol, Adelaide, SA, Australia. [Denton, Donna] Univ Adelaide, Sch Mol & Biomed Sci, Adelaide, SA, Australia. [Deretic, Vojo] Univ New Mexico, Hlth Sci Ctr, Dept Mol Genet & Microbiol, Albuquerque, NM 87131 USA. [Desai, Shyamal D.] Louisiana State Univ, Hlth Sci Ctr, Sch Med, Dept Biochem & Mol Biol, New Orleans, LA USA. [Devenish, Rodney J.; Mijaljica, Dalibor; Prescott, Mark; Ramm, Georg] Monash Univ, Dept Biochem & Mol Biol, Melbourne, Vic 3004, Australia. [Devenish, Rodney J.] Monash Univ, ARC Ctr Excellence Struct & Funct Microbial Genom, Melbourne, Vic 3004, Australia. [Di Gioacchino, Mario] Univ dAnnunzio Fdn, Ageing Res Ctr CeSI, Unit Allergy & Immunotoxicol, Chieti, Italy. [Di Paolo, Gilbert; Duff, Karen; Yu, Wai Haung] Columbia Univ, Med Ctr, Taub Inst Alzheimers Dis Res, New York, NY USA. [Di Paolo, Gilbert; Duff, Karen; Przedborski, Serge; Yamamoto, Ai; Yu, Wai Haung] Columbia Univ, Med Ctr, Dept Pathol & Cell Biol, New York, NY USA. [Di Pietro, Chiara; Marazziti, Daniela; Matteoni, Raffaele; Tocchini-Valentini, Glauco] EMMA CNR, Inst Cell Biol & Neurobiol, Rome, Italy. [Diaz-Araya, Guillermo] Univ Chile, Dept Pharmacol & Toxicol Chem, Santiago, Chile. [Diaz-Laviada, Ines] Univ Alcala De Henares, Sch Med, Dept Biochem & Mol Biol, Madrid, Spain. [Diaz-Meco, Maria T.; Fotedar, Rati; Hansen, Malene; Moscat, Jorge; Reed, John C.; Salvesen, Guy; Yang, Zhifen] Sanford Burnham Med Res Inst, La Jolla, CA USA. 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[Ganetzky, Barry] Univ Wisconsin, Genet Lab, Madison, WI 53706 USA. [Ganley, Ian G.] Univ Dundee, Coll Life Sci, MRC, Prot Phosphorylat Unit, Dundee, Scotland. [Gao, Fen-Biao] Univ Massachusetts, Sch Med, Dept Neurol, Worcester, MA USA. [Gao, George F.] Chinese Acad Sci, Inst Microbiol, CAS Key Lab Pathogen Microbiol & Immunol, Beijing, Peoples R China. [Gao, Jinming] UT SW Med Ctr, Dallas, TX USA. [Garcia, Lorena; Lavandero, Sergio] Univ Chile, Fac Med, Santiago 7, Chile. [Garcia, Lorena; Lavandero, Sergio] Univ Chile, Fac Ciencias Quim & Farmaceut, Ctr Estudios Mol Celula, Santiago 7, Chile. [Garcia-Manero, Guillermo] Univ Texas MD Anderson Canc Ctr, Dept Leukemia, Houston, TX 77030 USA. [Garcia-Marcos, Mikel] Boston Univ, Sch Med, Dept Biochem, Boston, MA 02118 USA. [Garmyn, Marjan] Katholieke Univ Leuven, Dept Oncol, Dermatol Lab, Louvain, Belgium. [Gartel, Andrei L.] Univ Illinois, Dept Med, Chicago, IL USA. [Gatti, Evelina; Golstein, Pierre; Pierre, Philippe] Univ Aix Marseille 2, Ctr Immunol Marseille Luminy, INSERM, UM2,U1104, F-13284 Marseille 07, France. [Gatti, Evelina; Golstein, Pierre; Pierre, Philippe] CNRS, UMR7280, Marseille, France. [Gautel, Mathias] Kings Coll London, Randall Div Cell & Mol Biophys, London WC2R 2LS, England. [Gautel, Mathias] Kings Coll London, Div Cardiovasc, London WC2R 2LS, England. [Gawriluk, Thomas R.; Hale, Amber N.; Ledbetter, Daniel J.; Rucker, Edmund B., III] Univ Kentucky, Dept Biol, Lexington, KY USA. [Gegg, Matthew E.; Schapira, Anthony H. V.] UCL, Inst Neurol, Dept Clin Neurosci, London, England. [Geng, Jiefei; Harper, J. Wade] Harvard Univ, Sch Med, Dept Cell Biol, Boston, MA USA. [Germain, Marc; Slack, Ruth S.] Univ Ottawa, Dept Cellular Mol Med, Ottawa, ON, Canada. [Gestwicki, Jason E.; Lieberman, Andrew; Lukacs, Nicholas W.] Univ Michigan, Dept Pathol, Ann Arbor, MI 48109 USA. [Ghavami, Saeid; Halayko, Andrew J.; Kirshenbaum, Lorrie A.; Yeganeh, Behzad] Univ Manitoba, Dept Physiol, Manitoba Inst Child Hlth, Winnipeg, MB R3T 2N2, Canada. [Ghosh, Pradipta; Lee, Jongdae] Univ Calif San Diego, Dept Med, La Jolla, CA 92093 USA. [Giammarioli, Anna M.; Malorni, Walter] Ist Super Sanita, Dept Therapeut Res & Med Evaluat, I-00161 Rome, Italy. [Giatromanolaki, Alexandra N.; Sivridis, Efthimios] Democritus Univ Thrace, Dept Pathol, Alexandroupolis, Greece. [Giatromanolaki, Alexandra N.; Sivridis, Efthimios] Univ Gen Hosp Alexandroupolis, Alexandroupolis, Greece. [Gibson, Spencer B.] Univ Manitoba, Manitoba Inst Cell Biol, Winnipeg, MB, Canada. [Gilkerson, Robert W.; Przedborski, Serge; Sulzer, David; Yamamoto, Ai] Columbia Univ, Dept Neurol, Med Ctr, New York, NY USA. [Ginger, Michael L.] Univ Lancaster, Sch Hlth & Med, Lancaster, England. [Ginsberg, Henry N.; Tabas, Ira] Columbia Univ, Coll Phys & Surg, Dept Med, New York, NY USA. [Golab, Jakub] Med Univ Warsaw, Dept Immunol, Warsaw, Poland. [Goligorsky, Michael S.] New York Med Coll, Renal Res Inst, Valhalla, NY 10595 USA. [Gomez-Manzano, Candelaria] Univ Texas MD Anderson Canc Ctr, Dept Genet, Houston, TX 77030 USA. [Goncu, Ebru] Ege Univ, Fac Sci, Dept Biol, Izmir, Turkey. [Gongora, Celine; Le Cam, Laurent; Legouis, Renaud; Pattingre, Sophie] Univ Montpellier I, INSERM, Inst Rech Cancerol Montpellier, U896, Montpellier, France. [Gonzalez, Claudio D.; Vaccaro, Maira I.] Univ Buenos Aires, Dept Pathophysiol, Sch Pharm & Biochem, Buenos Aires, DF, Argentina. [Gonzalez, Ramon] CSIC UR CAR, Inst Ciencias Vino, Logrono, Spain. [Gonzalez-Estevez, Cristina] Univ Nottingham, Queens Med Ctr, Ctr Genet & Genom, Dept Dev Genet & Gene Control, Nottingham NG7 2RD, England. [Gorbunov, Nikolai V.] Uniformed Serv Univ Hlth Sci, Henry M Jackson Fdn Adv Mil Med, Bethesda, MD 20814 USA. [Gorski, Sharon] BC Canc Agcy, Genome Sci Ctr, Vancouver, BC, Canada. [Goruppi, Sandro] Tufts Univ, Sch Med, Tufts Med Ctr, Mol Cardiol Res Inst, Boston, MA 02111 USA. [Goruppi, Sandro] Tufts Univ, Sch Med, Dept Med, Boston, MA 02111 USA. [Gozuacik, Devrim] Sabanci Univ, Biol Sci & Bioengn Program, Istanbul, Turkey. [Green, Kim N.] Univ Calif Irvine, Dept Neurobiol & Behav, Irvine, CA USA. [Gregorc, Ales] Agr Inst Slovenia, Ljubljana, Slovenia. [Gros, Frederic] Univ Strasbourg, CNRS, Strasbourg, France. [Grose, Charles] Univ Iowa, Dept Pediat, Childrens Hosp, Iowa City, IA 52242 USA. [Grunt, Thomas W.] Med Univ Vienna, Ctr Comprehens Canc, Dept Med 1, Signaling Networks Program,Div Oncol, Vienna, Austria. [Guan, Kun-Liang] Univ Calif San Diego, Dept Pharmacol, La Jolla, CA 92093 USA. [Guan, Kun-Liang] Univ Calif San Diego, Moores Canc Ctr, La Jolla, CA 92093 USA. [Gukovskaya, Anna S.; Gukovsky, Ilya] Univ Calif Los Angeles, David Geffen Sch Med, Dept Med, Los Angeles, CA 90095 USA. [Gunst, Jan; Van den Berghe, Greet; Vanhorebeek, Ilse] Katholieke Univ Leuven, Dept & Lab Intens Care Med, Louvain, Belgium. [Gustafsson, Asa B.] Univ Calif San Diego, Skaggs Sch Pharm & Pharmaceut Sci, San Diego, CA 92103 USA. [Halayko, Andrew J.] Univ Manitoba, Manitoba Inst Child Hlth, Dept Internal Med, Winnipeg, MB, Canada. [Halonen, Sandra K.] Montana State Univ, Dept Microbiol, Bozeman, MT 59717 USA. [Hamasaki, Maho; Noda, Takeshi; Yoshimori, Tamotsu] Osaka Univ, Dept Genet, Grad Sch Med, Osaka, Japan. [Han, Feng] Zhejiang Univ, Inst Pharmacol,Toxicol & Biochem Pharmaceut, Hangzhou 310003, Zhejiang, Peoples R China. [Hancock, Michael K.] Life Technol, Discovery & ADMET TOX Syst, Madison, WI USA. [Harada, Hisashi] Virginia Commonwealth Univ, Massey Canc Ctr, Dept Oral & Craniofacial Mol Biol, Richmond, VA USA. [Harada, Masaru] Univ Occupat & Environm Hlth, Sch Med, Dept Internal Med 3, Kitakyushu, Fukuoka 807, Japan. [Hardt, Stefan E.] Heidelberg Univ, Dept Cardiol Angiol & Pulmol, Heidelberg, Germany. [Harris, Adrian L.] Univ Oxford, John Radcliffe Hosp, Weatherall Inst Mol Med, Mol Oncol Labs,Dept Oncol, Oxford OX3 9DU, England. [Harris, James] Trinity Coll Dublin, Sch Biochem & Immunol, Immunol Res Ctr, Dublin, Ireland. [Harris, Steven D.] Univ Nebraska, Ctr Plant Sci Innovat, Lincoln, NE USA. [Hashimoto, Makoto] Tokyo Metropolitan Inst Med Sci, Div Sensory & Motor Syst, Tokyo 113, Japan. [Haspel, Jeffrey A.] VA Boston Healthcare Syst, Boston, MA USA. [Hayashi, Shin-ichiro] Natl Cerebral & Cardiovasc Ctr, Div Hypertens & Nephrol, Osaka, Japan. [Hayashi, Shin-ichiro] Gifu Univ, Grad Sch Med, Dept Cell Signalling, Gifu, Japan. [Hazelhurst, Lori A.] Univ S Florida, H Lee Moffitt Canc Ctr, Tampa, FL 33682 USA. [He, Congcong; Levine, Beth; Terada, Lance S.] Univ Texas SW Med Ctr Dallas, Howard Hughes Med Inst, Dallas, TX 75390 USA. [He, Congcong; Levine, Beth; Terada, Lance S.] Univ Texas SW Med Ctr Dallas, Dept Internal Med, Dallas, TX 75390 USA. [He, You-Wen; Rathmell, Jeffrey C.; Taylor, Gregory A.] Duke Univ, Med Ctr, Dept Immunol, Durham, NC USA. [Hebert, Marie-Josee] CRCHUM, Dept Nephrol, Montreal, PQ, Canada. [Heidenreich, Kim A.] Univ Colorado, Sch Med, Dept Pharmacol, Aurora, CO USA. [Helgason, Gudmundur V.; Holyoake, Tessa L.] Univ Glasgow, Inst Canc Sci, Coll Med Vet & Life Sci, Glasgow, Lanark, Scotland. [Herman, Brian; Reiter, Russel J.] Univ Texas Hlth Sci Ctr San Antonio, Dept Cellular & Struct Biol, San Antonio, TX 78229 USA. [Herman, Paul K.] Ohio State Univ, Dept Mol Genet, Columbus, OH 43210 USA. [Hetz, Claudio] Univ Chile, Fac Med, ICBM, Biomed Neurosci Inst, Santiago 7, Chile. [Hilfiker, Sabine; Navarro, Miguel] CSIC, IPBLN, Inst Parasitol & Biomed Lopez Neyra, Dept Mol Biol, Granada, Spain. [Hill, Joseph A.; Lavandero, Sergio; Nemchenko, Andriy] Univ Texas SW Med Ctr Dallas, Div Cardiol, Dallas, TX 75390 USA. [Hofmann, Thomas G.] DKFZ ZMBH Alliance, German Canc Res Ctr, Cellular Senescence Grp A210, Heidelberg, Germany. [Hoehfeld, Joerg] Univ Bonn, Inst Cell Biol, Bonn, Germany. [Hong, Ming-Huang] Sun Yat Sen Univ, GCP Ctr, Guangzhou 510275, Guangdong, Peoples R China. [Hood, David A.] York Univ, Sch Kinesiol & Hlth Sci, Toronto, ON M3J 2R7, Canada. [Hotamisligil, Goekhan S.] Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA. [Houwerzijl, Ewout J.] Univ Med Ctr Groningen, Dept Internal Med, NL-9713 AV Groningen, Netherlands. [Hoyer-Hansen, Maria] LEO Pharma AS, Dept Mol Biomed, Ballerup, Denmark. [Hu, Bingren] Univ Maryland, Sch Med, Shock Trauma & Anesthesiol Res Ctr, Baltimore, MD 21201 USA. [Hu, Chien-An A.] Univ New Mexico, Sch Med, Dept Biochem & Mol Biol, Albuquerque, NM 87131 USA. [Hu, Hong-Ming] Providence Portland Med Ctr, Earle A Chiles Res Inst, Lab Canc Immunobiol, Portland, OR USA. [Hua, Ya] Univ Michigan, Dept Neurosurg, Ann Arbor, MI 48109 USA. [Huang, Canhua; Liu, Bo] Sichuan Univ, State Key Lab Biotherapy, Chengdu 610064, Peoples R China. [Huang, Shengbing; Sinicrope, Frank A.] Mayo Clin, Dept Med, Rochester, MN USA. [Huang, Shengbing; Sinicrope, Frank A.] Mayo Canc Ctr, Rochester, MN USA. [Huang, Wei-Pang] Natl Taiwan Univ, Dept Life Sci, Taipei 10764, Taiwan. [Huang, Wei-Pang] Natl Taiwan Univ, Inst Zool, Taipei 10764, Taiwan. [Huber, Tobias B.] Univ Freiburg, BIOSS Ctr Biol Signalling Studies, D-79106 Freiburg, Germany. [Huber, Tobias B.] Univ Hosp Freiburg, Div Renal, Freiburg, Germany. [Huh, Won-Ki] Seoul Natl Univ, Sch Biol Sci, Seoul, South Korea. [Huh, Won-Ki] Seoul Natl Univ, Res Ctr Funct Cellul, Seoul, South Korea. [Hung, Tai-Ho] Chang Gung Mem Hosp, Dept Obstet & Gynecol, Taipei 10591, Taiwan. [Hupp, Ted R.] Univ Edinburgh, Dept Expt Canc Res, Inst Genet & Mol Med, Cell Signalling Unit, Edinburgh, Midlothian, Scotland. [Hur, Gang Min] Chungnam Natl Univ, Coll Med, Dept Pharmacol, Infect Signaling Network,Res Ctr, Taejon, South Korea. [Hurley, James B.] Univ Washington, Dept Biochem, Seattle, WA 98195 USA. [Hussain, Sabah N. A.] McGill Univ, Crit Care Dept, Montreal, PQ, Canada. [Hussey, Patrick J.] Univ Durham, Sch Biol & Biomed Sci, Durham, England. [Hwang, Jung Jin] Univ Ulsan, Coll Med, Inst Innovat Canc Res, Seoul, South Korea. [Hwang, Jung Jin] Asan Med Ctr, Seoul, South Korea. [Hwang, Seungmin] Washington Univ, Sch Med, Dept Pathol & Immunol, St Louis, MO USA. [Ichihara, Atsuhiro] Tokyo Womens Med Univ, Dept Med 2, Tokyo, Japan. [Inoki, Ken] Univ Michigan, Sch Med, Dept Internal Med, Div Nephrol, Ann Arbor, MI USA. [Inoki, Ken] Univ Michigan, Sch Med, Dept Mol & Integrat Physiol, Ann Arbor, MI USA. [Into, Takeshi] Asahi Univ, Sch Dent, Dept Oral Microbiol, Div Oral Infect & Hlth Sci, Mizuho, Japan. [Iovanna, Juan L.] Univ Aix Marseille 2, Marseille, France. [Iovanna, Juan L.] INSERM, U624, F-13258 Marseille, France. [Ip, Nancy Y.] Hong Kong Univ Sci & Technol, Div Life Sci, Hong Kong, Hong Kong, Peoples R China. [Ip, Nancy Y.] Hong Kong Univ Sci & Technol, State Key Lab Mol Neurosci, Hong Kong, Hong Kong, Peoples R China. [Isaka, Yoshitaka] Osaka Univ, Grad Sch Med, Dept Geriatr Med & Nephrol, Suita, Osaka, Japan. [Ishida, Hiroyuki] Tohoku Univ, Grad Sch Agr Sci, Dept Appl Plant Sci, Sendai, Miyagi 980, Japan. [Isobe, Ken-ichi] Nagoya Univ, Grad Sch Med, Dept Immunol, Nagoya, Aichi 4648601, Japan. [Iwasaki, Akiko] Yale Univ, Sch Med, Dept Immunobiol, New Haven, CT USA. [Izumi, Yotaro] Keio Univ, Sch Med, Divs Gen Thorac Surg, Tokyo, Japan. [Jaakkola, Panu M.] Univ Turku, Ctr Biotechnol, Turku, Finland. [Jackson, George R.] Univ Texas Med Branch, Dept Neurol, Galveston, TX USA. 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[Menzies, Fiona M.; Moreau, Kevin; Rubinsztein, David C.] Univ Cambridge, Dept Med Genet, Cambridge Inst Med Res, Cambridge, England. [Mercer, Carol A.] Univ Cincinnati, Dept Hematol Oncol, Cincinnati, OH USA. [Merry, Diane E.] Thomas Jefferson Univ, Dept Biochem & Mol Biol, Philadelphia, PA 19107 USA. [Meyer, Christian G.] Tropenmed Grundlagenforsch, Bernhard Nocht Inst Tropenmed, Hamburg, Germany. [Miao, Chao-Yu] Second Mil Med Univ, Dept Pharmacol, Shanghai, Peoples R China. [Miao, Jun-Ying] Shandong Univ, Sch Life Sci, Inst Dev Biol, Jinan 250100, Peoples R China. [Michiels, Carine] Univ Namur FUNDP, URBC NARILIS, Namur, Belgium. [Milojkovic, Ana] Max Delbruck Ctr Mol Med, Dept Mol Immunol & Gene Therapy, Berlin, Germany. [Miracco, Clelia] Univ Siena, Dept Human Pathol & Oncol, Sect Pathol Anat, I-53100 Siena, Italy. [Miranti, Cindy K.] Van Andel Res Inst, Lab Integrin Signaling, Grand Rapids, MI USA. 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Smith, Duncan /0000-0002-6592-9852; Sternberg, Cinthya/0000-0002-4760-6339; Johnson, Gail/0000-0003-3464-0404; Wang, Haichao/0000-0002-0211-9000; Clarke, Robert/0000-0002-9278-0854; Noda, Takeshi/0000-0003-3581-7961; Viola, Giampietro/0000-0001-9329-165X; Willbold, Dieter/0000-0002-0065-7366; Moreira, Paula/0000-0001-5177-6747; Yang, Shi Yu/0000-0001-8517-9238; Stork, Bjorn/0000-0002-4167-7806; Skulachev, Vladimir/0000-0003-4886-2243; Perry, George/0000-0002-6547-0172; Marino, Guillermo/0000-0003-1960-1677; Bridges, Dave/0000-0002-5334-972X; King, Jason/0000-0003-0596-4506; Siu, Parco/0000-0002-3548-5058; Aris, John/0000-0002-6475-064X; Hussey, Patrick/0000-0002-7349-8722; Garcia-Marcos, Mikel/0000-0001-9513-4826; Cardoso, Sandra M/0000-0002-2199-0555; Mollereau, Bertrand/0000-0003-4710-8185; Djavaheri-Mergny, Mojgan/0000-0003-4893-6505; Apostolova, Nadezda/0000-0002-4487-2471; Ledbetter, Daniel/0000-0002-5877-5904; Aguirre-Ghiso, Julio/0000-0002-6694-6507; Gibson, Spencer/0000-0003-0119-732X; Lee, Alvin/0000-0002-7427-9142; Franco, Rodrigo/0000-0003-3241-8615; brest, patrick/0000-0002-1252-4747; Revuelta, Jose/0000-0001-7838-5308; Jimenez, Alberto/0000-0003-3685-6479; Zaffaroni, Nadia/0000-0002-4669-0890; Novak, Ivana/0000-0003-0682-7052; AUBERGER, Patrick/0000-0002-2481-8275; Rocchi, Stephane/0000-0002-0943-1304; Lopez-Otin, Carlos/0000-0001-6964-1904; Chevet, Eric/0000-0001-5855-4522; Al-Younes, Hesham/0000-0002-8210-9514; Tettamanti, Gianluca/0000-0002-0665-828X; Fiorito, Filomena/0000-0002-6658-7807; Cho, Chi Hin/0000-0002-7658-3260; SOLDATI, Thierry/0000-0002-2056-7931; KIHARA, AKIO/0000-0001-5889-0788; McLaughlin, BethAnn/0000-0003-0228-6500; Travassos, Leonardo/0000-0003-1323-3797; Carra, Serena/0000-0003-0939-0140; SHEN, Han-Ming/0000-0001-7369-5227; Martinez-Vicente, Marta/0000-0001-7053-2625; Dikic, Ivan/0000-0001-8156-9511; MENENDEZ, JAVIER/0000-0001-8733-4561; Gonzalez Polo, Rosa-Ana/0000-0002-0163-2953; Menon, Manoj/0000-0001-5859-0347; Nakatogawa, Hitoshi/0000-0002-5828-0741; di Ronza, Alberto/0000-0002-9813-5143; Musaro, Antonio/0000-0002-2944-9739; Escalante, Ricardo/0000-0001-8547-531X; Soengas, Maria/0000-0003-0612-6299; Marchetti, Piero/0000-0003-4907-0635; Sanchez-Alcazar, Jose A./0000-0001-9705-1469; Johansen, Terje/0000-0003-1451-9578; Koh, Jae-Young/0000-0002-4318-495X; Koike, Masato/0000-0002-3174-5684; Votruba, Marcela/0000-0002-7680-9135; Segura-Aguilar, Juan/0000-0002-1018-673X; wang, baocheng/0000-0002-8236-8014; Zhang, Miqin/0000-0001-8974-1494; Lazo, Pedro /0000-0001-8997-3025; MESCHINI, STEFANIA/0000-0001-9079-1181; Crespo, Jose/0000-0003-3514-1025; Nguyen, Huu Phuc/0000-0001-6139-788X; Besteiro, Sebastien/0000-0003-1853-1494; Hilfiker, Sabine/0000-0002-5167-7682; Knecht, Erwin/0000-0002-7208-3832; Dreux, Marlene/0000-0002-6607-4796; Sanchez-Prieto, Ricardo/0000-0003-0882-9780; Cheng, Alan/0000-0001-7897-4751; Xie, Zhiping/0000-0001-5816-6159; Chen, Yongsheng/0000-0003-1448-8177; Navarro, Miguel/0000-0003-2301-2699; Thevissen, Karin/0000-0003-0275-9072; Talbot, Nicholas/0000-0001-6434-7757; GROS, Frederic/0000-0002-6252-4323; Petersen, Morten/0000-0002-3035-5991; Gegg, Matthew/0000-0001-8093-0723; Boya, Patricia/0000-0003-3045-951X; Rodriguez de Cordoba, Santiago/0000-0001-6401-1874; Chu, Charleen/0000-0002-5052-8271; Yoshimori, Tamotsu/0000-0001-9787-3788; GONZALEZ-REY, ELENA/0000-0003-3917-9020; Bortoluci, Karina /0000-0001-6780-5397; Liu, Yule/0000-0002-4423-6045; Yoon, Seung-Yong/0000-0003-0325-9993; Gorski, Sharon/0000-0002-3821-8289; Olsson, Stefan/0000-0003-1931-9081; Fuentes, Jose/0000-0001-6910-2089; Nezis, Ioannis/0000-0003-0233-7574; Malagoli, Davide/0000-0002-9857-8534; Linden, Rafael/0000-0003-3287-336X; Meyer, Thomas F./0000-0002-6120-8679; Wang, Xuejun/0000-0001-9267-1343; Diaz-Nido, Javier/0000-0002-0927-7925; Andrieu-Abadie, Nathalie/0000-0003-2698-1970; Golstein, Pierre/0000-0003-1750-3483; Yoshimoto, Kohki/0000-0003-3948-3751; Hetz, Claudio/0000-0001-7724-1767; Voitsekhovskaja, Olga/0000-0003-0966-1270; Mizushima, Noboru/0000-0002-6258-6444; Yuzaki, Michisuke/0000-0002-5750-3544; Golab, Jakub/0000-0002-2830-5100; Kim, Do-Hyung/0000-0002-2924-4370; Korolchuk, Viktor/0000-0002-4071-592X; Mottram, Jeremy/0000-0001-5574-3766; Marazziti, Daniela/0000-0002-1582-9271; SIMONE, Cristiano/0000-0002-2628-7658; Galliot, Brigitte/0000-0001-7596-8284; Gozuacik, Devrim/0000-0001-7739-2346; Fallon, Brian/0000-0003-1797-9713; Paris, Irmgard/0000-0003-2331-7513; legembre, patrick/0000-0001-6649-8049; Parys, Jan/0000-0002-3591-4967; HUANG, WEI-PANG/0000-0001-8410-6555; Marciniak, Stefan/0000-0001-8472-7183; Ryan, Kevin M./0000-0002-1059-9681; Marten, Mark/0000-0002-1863-8956; Brunetti-Pierri, Nicola/0000-0002-6895-8819; Almasan, Alex/0000-0002-8916-6650; Zhang, Xu Dong/0000-0001-9457-8003; Lee, Ju-hyun/0000-0002-0280-8375; Balduini, Walter/0000-0001-8438-9559; Mograbi, Baharia/0000-0002-1025-3429; Frankel, Lisa/0000-0001-7249-3607; Khalil, Hany/0000-0001-9738-4087; malorni, walter/0000-0002-1223-7000; Hocking, Lynne J/0000-0002-2414-2826; Rouschop, Kasper/0000-0002-4208-5415; Condorelli, Fabrizio/0000-0002-9943-0857; Palumbo, Camilla/0000-0001-5087-7140; Panaretakis, Theocharis/0000-0001-5754-6950; LIANG, CHENGYU/0000-0001-6082-2143; D'Amelio, Marcello/0000-0001-6526-1832; Bozhkov, Peter/0000-0002-8819-3884; Van der Klei, Ida J./0000-0001-7165-9679; Sinclair, David/0000-0002-9936-436X; De Felici, Massimo/0000-0001-8479-8264; Wang, Xinglong/0000-0001-8657-0159; Russo, Rossella/0000-0001-8758-6523; CASARI, Giorgio/0000-0002-0115-8980; gatti, evelina/0000-0002-0667-0799; Whitworth, Alexander/0000-0002-1154-6629; Grant, Gary/0000-0002-2574-5442; Berliocchi, Laura/0000-0002-3014-1838; FORNAI, FRANCESCO/0000-0002-3883-5084; SETTEMBRE, Carmine/0000-0002-5829-8589; Zhou, Cong-Zhao/0000-0002-6881-7151; CHEN, CHING-CHOW/0000-0002-7810-0939; Hofman, Paul/0000-0003-0431-9353; pierre, philippe/0000-0003-0863-8255; Ganley, Ian/0000-0003-1481-9407; Ko, Ben Chi Bun/0000-0003-2027-5899; Fox, Howard/0000-0003-2032-374X; McInerney, Gerald/0000-0003-2257-7241; Low, Peter/0000-0003-2450-7087; De Milito, Angelo/0000-0003-2591-2914; Leiro Vidal, Jose Manuel/0000-0001-6963-515X; Chisari, Francis/0000-0002-4832-1044; Isidoro, Ciro/0000-0002-5494-3034; BRANCOLINI, Claudio/0000-0002-6597-5373; Lavandero, Sergio/0000-0003-4258-1483; holyoake, tessa/0000-0002-0608-6066; Kramer, Helmut/0000-0002-1167-2676; Gaestel, Matthias/0000-0002-4944-4652; Cadwell, Ken/0000-0002-5860-0661; Simon, Hans-Uwe/0000-0002-9404-7736; Espina, Virginia/0000-0001-5080-5972; Lingor, Paul/0000-0001-9362-7096; Jung, Yong-Keun/0000-0002-9686-3120; Hwang, Seungmin/0000-0003-0846-5462; Clague, Michael/0000-0003-3355-9479; Scorrano, Luca/0000-0002-8515-8928; Demarchi, Francesca/0000-0003-1565-3162; Ruiz-Opazo, Nelson/0000-0001-8234-1332; Zhivotovsky, Boris/0000-0002-2238-3482; Deretic, Vojo/0000-0002-3624-5208; COTO-MONTES, ANA/0000-0002-6609-6258; Lund, Anders/0000-0002-7407-3398; Marambaud, Philippe/0000-0002-8983-1497; BALLABIO, Andrea/0000-0003-1381-4604; YUN, Cheol-Heui/0000-0002-0041-2887; Wu, Daocheng/0000-0002-6183-539X; Simonsen, Anne/0000-0003-4711-7057; Tonges, Lars/0000-0001-6621-144X; Liton, Paloma/0000-0002-1440-3762; Subauste, Carlos/0000-0002-5602-1439; Cecconi, Francesco/0000-0002-5614-4359; Kanneganti, Thirumala-Devi/0000-0002-6395-6443; Mostowy, Serge/0000-0002-7286-6503; Nakano, Hiroyasu/0000-0003-4843-1427; Bultynck, Geert/0000-0002-5968-4828; Ginger, Michael/0000-0002-9643-8482; Bechet, Daniel/0000-0002-3812-8099; Lin, Wan Wan/0000-0002-3207-734X; Kehrl, John/0000-0002-6526-159X; Macian, Fernando/0000-0003-2666-035X; Carding, Simon/0000-0002-2383-9701; Piras, Antonio/0000-0003-3052-1715; Harris, Adrian/0000-0003-1376-8409; Egea, Gustavo/0000-0001-5242-150X; MATTEONI, RAFAELE/0000-0002-0314-5948; Kaminskyy, Vitaliy/0000-0002-8151-5270; /0000-0003-3505-3674; Wouters, Bradly/0000-0002-8187-592X; Kaarniranta, Kai/0000-0003-2600-8679; Kabuta, Tomohiro/0000-0002-3058-2596; Jaattela, Marja/0000-0001-5950-7111; Kumar, Sharad/0000-0001-7126-9814; Weiss, William/0000-0003-2230-9132; Tschan, Mario P./0000-0001-5897-3647; Zacks, David/0000-0001-8592-5165; Nishino, Ichizo/0000-0001-9452-112X; Kim, Yonghyun/0000-0001-6344-1258; Zhu, Wei-Guo/0000-0001-8385-6581; Merighi, Adalberto/0000-0002-1140-3556; Engelbrecht, Anna-Mart/0000-0003-1469-0148; Skop, Vojtech/0000-0002-4685-4429; Batoko, Henri/0000-0002-8256-519X; Schiaffino, Stefano/0000-0002-5607-6421; Munger, Karl/0000-0003-3288-9935; Chen, Quan/0000-0001-7539-8728 FU National Institutes of Health Public Health Service [GM53396] FX In a rapidly expanding and highly dynamic field such as autophagy, it is possible that some authors who should have been included on this manuscript have been missed. D.J.K. extends his apologies to researchers in the field of autophagy who, due to oversight or any other reason, could not be included. This work was supported by National Institutes of Health Public Health Service grant GM53396 to D.J.K. Due to space and other limitations, it is not possible to include all other sources of financial support. NR 884 TC 1731 Z9 1809 U1 266 U2 2286 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 530 WALNUT STREET, STE 850, PHILADELPHIA, PA 19106 USA SN 1554-8627 EI 1554-8635 J9 AUTOPHAGY JI Autophagy PD APR PY 2012 VL 8 IS 4 BP 445 EP 544 DI 10.4161/auto.19496 PG 100 WC Cell Biology SC Cell Biology GA 960QQ UT WOS:000305403400002 PM 22966490 ER PT J AU Marotta, F Naito, Y Jain, S Lorenzetti, A Soresi, V Kumari, A Bastos, PC Tomella, C Yadav, H AF Marotta, F. Naito, Y. Jain, S. Lorenzetti, A. Soresi, V. Kumari, A. Bastos, P. Carrera Tomella, C. Yadav, H. TI IS THERE A POTENTIAL APPLICATION OF A FERMENTED NUTRACEUTICAL IN ACUTE RESPIRATORY ILLNESSES? AN IN-VIVO PLACEBO-CONTROLLED, CROSS-OVER CLINICAL STUDY IN DIFFERENT AGE GROUPS OF HEALTHY SUBJECTS SO JOURNAL OF BIOLOGICAL REGULATORS AND HOMEOSTATIC AGENTS LA English DT Article DE fermented papaya preparation; epigenomic modification; nasal lavage ID EXTRACELLULAR-SUPEROXIDE DISMUTASE; INFLUENZA-VIRUS INFECTION; PAPAYA PREPARATION; NITRIC-OXIDE; OXIDATIVE DAMAGE; IMMUNOGLOBULIN-A; OXYGEN RADICALS; LUNG; MICE; PATHOGENESIS AB The role of oxidants in viral diseases is fairly complex because it includes metabolic regulation both of host metabolism and viral replication. However, a role for reactive oxygen species (ROS) and reactive nitrogen species (RNS) as mediators of virus-induced lung damage is supported by studies and antioxidants can thus be expected to act at many different levels. The aim of the present pilot study was to test an antioxidant nutraceutical approach on some relevant immunological parameters known to be affected in common seasonal respiratory tract infection. The study population consisted of 90 sedentary healthy patients, previously selected as being GSTM1-positive, divided into three groups: A) 20-40 years; B) 41-65 years; B) over 65 years. Each patients was administered a life style and dietary questionnaire. Subjects were supplemented for 6 weeks with either 9g/day (4.5g twice a day sublingually) of a fermented papaya preparation (Osato Research Institute, Gifu, Japan) or placebo. After a further month period of wash out, subjects were treated again in a crossover manner. Parameters checked were as fellows: routine blood tests with WBC formula, saliva flow rate and secretary IgA and lysozyme production and redox gene expression of Phase II enzyme and SOD from upper airways cells (from nasal lavage). Salivary secretion rate showed an age-related decline and was significantly increased by FPP supplementation only in the youngest age-group (p<0.05). Subjects treated with FPP showed a significantly higher lever of IgA and lisozyme production., irrespective of age group while their baseline production was significantly lower in the oldest age-group as compared to the youngest one (C vs A, p<0.05). FPP treatment brought about a significant upregulation of all phase II enzyme and SOD gene expression tested in nasal lavage cells. In conclusion, FPP supplementation during 1 month resulted in higher salivary IgA and increase in phase II and SOD enzyme expression, i.e the most important antioxidant in the respiratory tract. The biological significance of these effects i.e., whether it will help reducing the whole respiratory oxidative stress in the human airway and, hopefully, the incidence and/or severity of URTI remains to be demonstrated in longer clinical trials. C1 [Marotta, F.; Lorenzetti, A.; Soresi, V.; Tomella, C.] ReGenera Res Grp Aging Intervent, Milan, Italy. [Naito, Y.] Immunol Res Inst & Clin, Nagoya, Aichi, Japan. [Jain, S.; Yadav, H.] NIDDK, NIH, Bethesda, MD USA. [Kumari, A.] Univ Quebec, Ctr Eau Terre & Environm, Inst Natl Rech Sci, Quebec City, PQ, Canada. [Bastos, P. Carrera] Lund Univ Malmo, Fac Med, Ctr Primary Hlth Care Res, Malmo, Sweden. RP Marotta, F (reprint author), Piazza Firenze 12, I-20154 Milan, Italy. EM fmarchimede@libero.it NR 41 TC 7 Z9 7 U1 0 U2 3 PU BIOLIFE SAS PI SILVA MARINA (TE) PA VIA S STEFANO 39 BIS, 64029 SILVA MARINA (TE), ITALY SN 0393-974X J9 J BIOL REG HOMEOS AG JI J. Biol. Regul. Homeost. Agents PD APR-JUN PY 2012 VL 26 IS 2 BP 285 EP 294 PG 10 WC Endocrinology & Metabolism; Immunology; Medicine, Research & Experimental; Physiology SC Endocrinology & Metabolism; Immunology; Research & Experimental Medicine; Physiology GA 982HX UT WOS:000307034900014 PM 22824755 ER PT J AU Pisetsky, DS Ward, MM AF Pisetsky, David S. Ward, Michael M. TI Advances in the treatment of inflammatory arthritis SO BEST PRACTICE & RESEARCH IN CLINICAL RHEUMATOLOGY LA English DT Article DE Rheumatoid arthritis; Spondyloarthritis; Ankylosing spondylitis ID EARLY RHEUMATOID-ARTHRITIS; SOCIETY CLASSIFICATION CRITERIA; GENOME-WIDE ASSOCIATION; ANKYLOSING-SPONDYLITIS; PSORIATIC-ARTHRITIS; SUSCEPTIBILITY LOCI; AMERICAN-COLLEGE; DOUBLE-BLIND; BACK-PAIN; RHEUMATOLOGY/EUROPEAN LEAGUE AB The inflammatory arthritides are a diverse group of conditions characterised by joint inflammation which can lead to pain, deformity and disability. Of these diseases, rheumatoid arthritis (RA) and spondyloarthritis are two of the most common. While the clinical and demographic features of these diseases differ, the central role of inflammation in their pathogenesis has allowed the development of highly effective treatment strategies with wide applicability. These strategies include the use of biological agents which target the cytokine tumour necrosis factor (TNF), a key mediator of inflammation. With the advent of effective agents, therapy has become more aggressive, reducing disease activity and allowing, at least in RA, remission in many patients. While the array of available effective treatments is extensive, the use of objective measures of disease activity can guide treatment decisions (treat to target) and lead to improved outcomes. (C) 2012 Published by Elsevier Ltd. C1 [Pisetsky, David S.] Durham VA Hosp, Med Res Serv, Durham, NC 27705 USA. [Pisetsky, David S.] Duke Univ, Med Ctr, Dept Med, Durham, NC 27705 USA. [Ward, Michael M.] NIAMS, NIH, IRP, Bethesda, MD 20892 USA. RP Pisetsky, DS (reprint author), Durham VA Hosp, Med Res Serv, 151G Durham VAMC,508 Fulton St, Durham, NC 27705 USA. EM dpiset@duke.edu; wardm1@mail.nih.gov FU VA Merit Review grant; NIH [AI083923] FX These studies were supported by a VA Merit Review grant and NIH grant AI083923. NR 55 TC 10 Z9 13 U1 0 U2 3 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 1521-6942 J9 BEST PRACT RES CL RH JI Best Pract. Res. Clin. Rheumatol. PD APR PY 2012 VL 26 IS 2 BP 251 EP 261 DI 10.1016/j.berh.2012.03.001 PG 11 WC Rheumatology SC Rheumatology GA 983RA UT WOS:000307135200007 PM 22794097 ER PT J AU Tsujimoto, T Sasai, H Miyashita, M Eto, M So, RN Ohkubo, H Tanaka, K AF Tsujimoto, Takehiko Sasai, Hiroyuki Miyashita, Masashi Eto, Miki So, Rina Ohkubo, Hiroyuki Tanaka, Kiyoji TI Effect of weight loss on maximal fat oxidation rate in obese men SO OBESITY RESEARCH & CLINICAL PRACTICE LA English DT Article DE Obesity; Weight loss; Maximal fat oxidation rate ID HUMAN SKELETAL-MUSCLE; INSULIN-RESISTANCE; EXERCISE INTENSITY; LIPID OXIDATION; RESPIRATORY QUOTIENT; INDIRECT CALORIMETRY; SUBSTRATE OXIDATION; PHYSICAL-ACTIVITY; BODY-COMPOSITION; GRADED-EXERCISE AB Introduction: The hallmark features of obesity include insulin resistance and an impaired ability to oxidize lipids. As compared to exercise training, it remains relatively unclear if diet-induced weight loss can also induce fat metabolism. This study was undertaken to examine the effects of diet-induced weight loss on fat metabolism during a single session of exercise in middle-aged obese men. Methods: Fifteen obese men who were otherwise healthy (average age of 53.5 +/- 6.9 yr and average body mass index of 27.8 +/- 1.6 kg/m(2)) participated in a 12-wk weight loss program primarily consisting of dietary modification. Maximal fat oxidation (MFO) rates, MFO per lean body mass (MFOLBM) and insulin resistance (HOMA-IR) were measured before and after the program. Participants performed a 24-min graded exercise test on a cycle ergometer, with 15-W increments every 4 min. Expired gas analysis was performed by indirect calorimetry, and nonprotein respiratory quotient equations were used to calculate fat oxidation rates. Results: The weight (-8.3 +/- 3.8 kg), fat mass (-4.5 +/- 1.9 kg), and lean body mass (-3.8 +/- 2.4 kg) (P < 0.001 for all measurements) of the participants were decreased at the end of the 12-wk program. The MFO tended to increase by 19% (P = 0.08) and MFOLBM significantly increased by 28.8% (P = 0.02). Although insulin resistance also significantly decreased by 49% (P < 0.001), changes in fat oxidation variables did not correlate with changes in insulin resistance. Conclusion: Diet-induced weight loss improves fat metabolism with the improvement in insulin resistance. (C) 2011 Asian Oceanian Association for the Study of Obesity. Published by Elsevier Ltd. All rights reserved. C1 [Tsujimoto, Takehiko; Eto, Miki; So, Rina; Ohkubo, Hiroyuki; Tanaka, Kiyoji] Univ Tsukuba, Grad Sch Comprehens Human Sci, Tsukuba, Ibaraki 3058577, Japan. [Sasai, Hiroyuki] NIDDKD, Diabet Endocrinol & Obes Branch, NIH, Bethesda, MD 20892 USA. [Sasai, Hiroyuki] Japan Soc Promot Sci, Tokyo, Japan. [Miyashita, Masashi] Waseda Univ, Fac Sport Sci, Saitama, Japan. RP Tsujimoto, T (reprint author), Univ Tsukuba, Grad Sch Comprehens Human Sci, 1-1-1 10-Nodai, Tsukuba, Ibaraki 3058577, Japan. EM tsujimoto@stat.taiiku.tsukuba.ac.jp OI Sasai, Hiroyuki/0000-0001-8120-6163 FU Japanese Ministry of Education, Culture, Sports, Science and Technology FX This work was supported by a grant-in aid from the Japanese Ministry of Education, Culture, Sports, Science and Technology (2008-2010, Tanaka Project). NR 46 TC 3 Z9 3 U1 1 U2 12 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 1871-403X J9 OBES RES CLIN PRACT JI Obes. Res. Clin. Pract. PD APR-JUN PY 2012 VL 6 IS 2 BP E111 EP E119 DI 10.1016/j.orcp.2011.06.003 PG 9 WC Endocrinology & Metabolism; Nutrition & Dietetics SC Endocrinology & Metabolism; Nutrition & Dietetics GA 981HI UT WOS:000306957200003 ER PT J AU Darlow, S Goodman, MS Stafford, JD Lachance, CR Kaphingst, KA AF Darlow, Susan Goodman, Melody S. Stafford, Jewel D. Lachance, Christina R. Kaphingst, Kimberly A. TI Weight Perceptions and Perceived Risk for Diabetes and Heart Disease Among Overweight and Obese Women, Suffolk County, New York, 2008 SO PREVENTING CHRONIC DISEASE LA English DT Article ID HEALTH LITERACY; UNITED-STATES; VITAL SIGN; US ADULTS; ASSOCIATION; PREVALENCE; KNOWLEDGE; MORTALITY; OUTCOMES; TRENDS AB Introduction Many Americans fail to accurately identify themselves as overweight and underestimate their risk for obesity-related diseases. The purpose of this study was to investigate associations between weight perceptions and perceived risk for diabetes and heart disease among overweight or obese women. Methods We examined survey responses from 397 overweight or obese female health center patients on disease risk perceptions and weight perceptions. We derived odds ratios (ORs) and 95% confidence intervals (CIs) from multivariable logistic regression analyses to examine predictors of perceived risk for diabetes and heart disease. We further stratified results by health literacy. Results Perceiving oneself as overweight (OR, 2.78; 95% CI, 1.16-6.66), believing that being overweight is a personal health problem (OR, 2.46; 95% CI, 1.26-4.80), and family history of diabetes (OR, 3.22; 95% CI, 1.53-6.78) were associated with greater perceived risk for diabetes. Perceiving oneself as overweight (OR, 4.33; 95% CI, 1.26-14.86) and family history of heart disease (OR, 2.25; 95% CI, 1.08-4.69) were associated with greater perceived risk for heart disease. Among respondents with higher health literacy, believing that being overweight was a personal health problem was associated with greater perceived risk for diabetes (OR, 4.91; 95% CI, 1.68-14.35). Among respondents with lower health literacy, perceiving oneself as overweight was associated with greater perceived risk for heart disease (OR, 4.69; 95% CI, 1.02-21.62). Conclusion Our findings indicate an association between accurate weight perceptions and perceived risk for diabetes and heart disease in overweight or obese women. This study adds to research on disease risk perceptions in at-risk populations. C1 [Goodman, Melody S.; Stafford, Jewel D.; Kaphingst, Kimberly A.] Washington Univ, Sch Med, St Louis, MO USA. [Lachance, Christina R.] NHGRI, NIH, Bethesda, MD 20892 USA. RP Darlow, S (reprint author), Fox Chase Canc Ctr, Canc Prevent & Control Program, Room P4159,333 Cottman Ave, Philadelphia, PA 19111 USA. EM susan.darlow@fccc.edu RI Goodman, Melody/F-6768-2011 OI Goodman, Melody/0000-0001-8932-624X FU National Human Genome Research Institute at the National Institutes of Health; Barnes-Jewish Hospital Foundation FX This research was funded by the National Human Genome Research Institute at the National Institutes of Health. Drs Goodman and Kaphingst were also supported by funding from the Barnes-Jewish Hospital Foundation. NR 30 TC 2 Z9 2 U1 1 U2 13 PU CENTERS DISEASE CONTROL PI ATLANTA PA 1600 CLIFTON RD, ATLANTA, GA 30333 USA SN 1545-1151 J9 PREV CHRONIC DIS JI Prev. Chronic Dis. PD APR PY 2012 VL 9 AR 110185 DI 10.5888/pcd9.110185 PG 8 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 977HL UT WOS:000306647200002 ER PT J AU Geyer, CB Saba, R Kato, Y Anderson, AJ Chappell, VK Saga, Y Eddy, EM AF Geyer, Christopher B. Saba, Rie Kato, Yuzuru Anderson, Amy J. Chappell, Vesna K. Saga, Yumiko Eddy, Edward M. TI Rhox13 Is Translated in Premeiotic Germ Cells in Male and Female Mice and Is Regulated by NANOS2 in the Male SO BIOLOGY OF REPRODUCTION LA English DT Article DE meiosis; NANOS2; retinoic acid; Rhox13; testis; translation ID ACID GENE-8 STRA8; RETINOIC ACID; MEIOTIC INITIATION; CHROMOSOME CONDENSATION; SPERMATOGENIC CELLS; SUPPRESSES MEIOSIS; HOMEOBOX GENE; MOUSE; EXPRESSION; OOGENESIS AB Male and female germ cells enter meiosis in response to an extrinsic cue by retinoic acid (RA), but the pathways downstream of RA signaling that regulate early gametogenesis remain uncertain. We identified a novel reproductive homeobox gene, Rhox13, transcribed in the prenatal ovary and testis beginning on Embryonic Day (E) 13.5. Translation of RHOX13 also begins in female germ cells on E13.5 but is suppressed in male germ cells until Postnatal Day 3. Translation of RHOX13 coincides with initiation of RA signaling in both male and female gonads in vivo but occurs precociously in neonatal testes exposed to RA in vitro or in fetal male germ cells when NANOS2 is absent in vivo. Conversely, RHOX13 translation in female germ cells is suppressed in the presence of ectopically induced NANOS2. These results strongly suggest that RHOX13 expression is regulated at a posttranscriptional step by direct interaction of NANOS2 with Rhox13 mRNA to suppress translation. C1 [Geyer, Christopher B.; Chappell, Vesna K.] E Carolina Univ, Dept Anat & Cell Biol, Brody Sch Med, Greenville, NC 27834 USA. [Geyer, Christopher B.; Anderson, Amy J.; Eddy, Edward M.] NIEHS, Gamete Biol Grp, Lab Reprod & Dev Toxicol, NIH, Res Triangle Pk, NC 27709 USA. [Saba, Rie; Kato, Yuzuru; Saga, Yumiko] Natl Inst Genet, Div Mammalian Dev, Mishima, Shizuoka 411, Japan. RP Geyer, CB (reprint author), E Carolina Univ, Dept Anat & Cell Biol, Brody Sch Med, 600 Moye Blvd, Greenville, NC 27834 USA. EM geyerc@ecu.edu FU NIH, National Institute of Environmental Health Sciences [ZO1-ES070076]; Ministry of Education, Culture, Sports, Science and Technology, Japan FX Supported in part by the Intramural Research Program of the NIH, National Institute of Environmental Health Sciences (ZO1-ES070076, EME) and in part by Grants-in-Aid for Scientific Research (S) of the Ministry of Education, Culture, Sports, Science and Technology, Japan. NR 45 TC 10 Z9 11 U1 0 U2 4 PU SOC STUDY REPRODUCTION PI MADISON PA 1691 MONROE ST,SUITE # 3, MADISON, WI 53711-2021 USA SN 0006-3363 J9 BIOL REPROD JI Biol. Reprod. PD APR PY 2012 VL 86 IS 4 AR 127 DI 10.1095/biolreprod.111.094938 PG 9 WC Reproductive Biology SC Reproductive Biology GA 975ZE UT WOS:000306549500015 PM 22190708 ER PT J AU Subbaramaiah, K Morris, PG Zhou, XK Morrow, M Du, BH Giri, D Kopelovich, L Hudis, CA Dannenberg, AJ AF Subbaramaiah, Kotha Morris, Patrick G. Zhou, Xi Kathy Morrow, Monica Du, Baoheng Giri, Dilip Kopelovich, Levy Hudis, Clifford A. Dannenberg, Andrew J. TI Increased Levels of COX-2 and Prostaglandin E-2 Contribute to Elevated Aromatase Expression in Inflamed Breast Tissue of Obese Women SO CANCER DISCOVERY LA English DT Article ID TUMOR-NECROSIS-FACTOR; ADIPOSE-TISSUE; GENE-EXPRESSION; POSTMENOPAUSAL WOMEN; INSULIN-RESISTANCE; CANCER CELLS; FACTOR-ALPHA; CYCLOOXYGENASE-2; INFLAMMATION; MACROPHAGES AB Obesity is a risk factor for hormone receptor-positive breast cancer in post-menopausal women. Estrogen synthesis is catalyzed by aromatase, which is encoded by CYP19. We previously showed that aromatase expression and activity are increased in the breast tissue of overweight and obese women in the presence of characteristic inflammatory foci [crown-like structures of the breast (CLS-B)]. In preclinical studies, proinflammatory prostaglandin E-2 (PGE(2)) is a determinant of aromatase expression. We provide evidence that cyclooxygenase (COX)-2-derived PGE(2) stimulates the cyclic AMP (cAMP)-> PKA signal transduction pathway that activates CYP19 transcription, resulting in increased aromatase expression and elevated progesterone receptor levels in breast tissues from overweight and obese women. We further demonstrate that a measure of in-breast inflammation (CLS-B index) is a better correlate of these biologic end points than body mass index. The obesity -> inflammation -> aromatase axis is likely to contribute to the increased risk of hormone receptor-positive breast cancer and the worse prognosis of obese patients with breast cancer. SIGNIFICANCE: We show that obesity-associated inflammatory foci in the human breast are associated with elevated COX-2 levels and activation of the PGE(2)-> cAMP -> PKA signal transduction pathway resulting in increased aromatase expression. These findings help to explain the link among obesity, low-grade chronic inflammation, and breast cancer with important clinical implications. Cancer Discov; 2(4); 356-65. (c) 2012 AACR. C1 [Subbaramaiah, Kotha; Du, Baoheng; Hudis, Clifford A.; Dannenberg, Andrew J.] Weill Cornell Canc Ctr, Dept Med, New York, NY 10065 USA. [Zhou, Xi Kathy] Weill Cornell Canc Ctr, Dept Publ Hlth, New York, NY 10065 USA. [Morris, Patrick G.; Hudis, Clifford A.] Mem Sloan Kettering Canc Ctr, Dept Med, New York, NY 10021 USA. [Morrow, Monica] Mem Sloan Kettering Canc Ctr, Dept Surg, New York, NY 10021 USA. [Giri, Dilip] Mem Sloan Kettering Canc Ctr, Dept Pathol, New York, NY 10021 USA. [Kopelovich, Levy] NCI, Canc Prevent Div, Bethesda, MD 20892 USA. RP Dannenberg, AJ (reprint author), Weill Cornell Canc Ctr, Dept Med, 525 E 68th St,Room F-206, New York, NY 10065 USA. EM ksubba@med.cornell.edu; ajdannen@med.cornell.edu FU National Cancer Institute [1R01CA154481, N01-CN-43302]; Breast Cancer Research Foundation; Botwinick-Wolfensohn Foundation; Kochavi Breast Cancer Prevention Fund; Metastasis Research Center of Memorial Sloan-Kettering Cancer Center FX This work was supported by National Cancer Institute 1R01CA154481 and N01-CN-43302 (to A.J. Dannenberg), the Breast Cancer Research Foundation (to A.J. Dannenberg and C.A. Hudis), the Botwinick-Wolfensohn Foundation [in memory of Mr. and Mrs. Benjamin Botwinick (to A.J. Dannenberg)], the Kochavi Breast Cancer Prevention Fund (to C.A. Hudis), and the Metastasis Research Center of Memorial Sloan-Kettering Cancer Center (to C.A. Hudis). The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Cancer Institute or the NIH. NR 40 TC 98 Z9 99 U1 0 U2 9 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 2159-8274 J9 CANCER DISCOV JI Cancer Discov. PD APR PY 2012 VL 2 IS 4 BP 356 EP 365 DI 10.1158/2159-8290.CD-11-0241 PG 10 WC Oncology SC Oncology GA 973BP UT WOS:000306327000029 PM 22576212 ER PT J AU Blair, KS Blair, RJR AF Blair, Karina S. Blair, R. J. R. TI A Cognitive Neuroscience Approach to Generalized Anxiety Disorder and Social Phobia SO EMOTION REVIEW LA English DT Article DE conditioning; emotion regulation; generalized anxiety disorder; social phobia; social threat processing ID AMYGDALA ACTIVATION; PREFRONTAL CORTEX; EMOTIONAL FACES; FACIAL EXPRESSIONS; ANTERIOR CINGULATE; TREATMENT RESPONSE; BRAIN ACTIVATION; ATTENTIONAL BIAS; FUNCTIONAL MRI; ANGRY AB Generalized anxiety disorder (GAD) and social phobia (SP) are major anxiety disorders identified by the Diagnostic and Statistical Manual of Mental Disorders, 4th edition (DSM-IV). They are comorbid, overlap in symptoms, yet present with distinct features (worry in GAD and fear of embarrassment in SP). Both have also been explained in terms of conditioning-based models. However, there is little reasoning currently to believe that GAD in adulthood reflects heightened conditionability or heightened threat processing-though patients with SP may show heightened processing of social threat stimuli. Moreover, the computational architectures that maintain these disorders in adulthood are different. For GAD this may reflect the development of an inefficient "worrying" strategy of emotional regulation. For SP this appears to reflect the atypical processing of self-referential information. C1 [Blair, Karina S.; Blair, R. J. R.] NIMH, Mood & Anxiety Program, NIH, Dept Hlth & Human Serv, Bethesda, MD 20892 USA. RP Blair, KS (reprint author), NIMH, Mood & Anxiety Program, NIH, Dept Hlth & Human Serv, 15K North Dr,MSC 2670, Bethesda, MD 20892 USA. EM peschark@mail.nih.gov NR 56 TC 9 Z9 9 U1 17 U2 41 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 1754-0739 J9 EMOT REV JI Emot. Rev. PD APR PY 2012 VL 4 IS 2 BP 133 EP 138 DI 10.1177/1754073911430251 PG 6 WC Psychology, Multidisciplinary SC Psychology GA 972KN UT WOS:000306276100004 ER PT J AU Wang, S Xiong, W Ma, WP Chanock, S Jedrychowski, W Wu, RL Perera, FP AF Wang, Shuang Xiong, Wei Ma, Weiping Chanock, Stephen Jedrychowski, Wieslaw Wu, Rongling Perera, Frederica P. TI Gene-Environment Interactions on Growth Trajectories SO GENETIC EPIDEMIOLOGY LA English DT Article DE gene-environment interactions; growth curves; Wald test; parametric bootstrap ID POLYCYCLIC AROMATIC-HYDROCARBONS; PAH-DNA ADDUCTS; PRENATAL EXPOSURE; CHILDREN; POLYMORPHISMS; INTELLIGENCE; FETAL; AGE; BENZO(A)PYRENE; LIFE AB It has been suggested that children with larger brains tend to perform better on IQ tests or cognitive function tests. Prenatal head growth and head growth in infancy are two crucial periods for subsequent intelligence. Studies have shown that environmental exposure to air pollutants during pregnancy is associated with fetal growth reduction, developmental delay, and reduced IQ. Meanwhile, genetic polymorphisms may modify the effect of environment on head growth. However, studies on gene-environment or gene-gene interactions on growth trajectories have been quite limited partly due to the difficulty to quantitatively measure interactions on growth trajectories. Moreover, it is known that assessing the significance of gene-environment or gene-gene interactions on cross-sectional outcomes empirically using the permutation procedures may bring substantial errors in the tests. We proposed a score that quantitatively measures interactions on growth trajectories and developed an algorithm with a parametric bootstrap procedure to empirically assess the significance of the interactions on growth trajectories under the likelihood framework. We also derived a Wald statistic to test for interactions on growth trajectories and compared it to the proposed parametric bootstrap procedure. Through extensive simulation studies, we demonstrated the feasibility and power of the proposed testing procedures. We applied our method to a real dataset with head circumference measures from birth to age 7 on a cohort currently being conducted by the Columbia Center for Children's Environmental Health (CCCEH) in Krakow, Poland, and identified several significant gene-environment interactions on head circumference growth trajectories. Genet. Epidemiol. 36:206-213, 2012. (C) 2012 Wiley Periodicals, Inc. C1 [Wang, Shuang; Xiong, Wei] Columbia Univ, Dept Biostat, Mailman Sch Publ Hlth, New York, NY 10032 USA. [Ma, Weiping] Fudan Univ, Sch Math Sci, Shanghai 200433, Peoples R China. [Chanock, Stephen] NCI, Bethesda, MD 20892 USA. [Jedrychowski, Wieslaw] Jagiellonian Univ, Dept Epidemiol & Prevent Med, Coll Med, Krakow, Poland. [Jedrychowski, Wieslaw; Perera, Frederica P.] Columbia Univ, Columbia Ctr Childrens Environm Hlth, Mailman Sch Publ Hlth, New York, NY 10032 USA. [Wu, Rongling] Penn State Univ, Ctr Stat Genet, Hershey, PA USA. RP Wang, S (reprint author), Columbia Univ, Dept Biostat, Mailman Sch Publ Hlth, 722 W 168th St,Room 630, New York, NY 10032 USA. EM sw2206@columbia.edu FU National Institute of Environmental Health Sciences [P01 ES09600, R01 ES08977, P50ES015905] FX Contract grant sponsor: National Institute of Environmental Health Sciences; Contract grant numbers: P01 ES09600, R01 ES08977, P50ES015905. NR 29 TC 1 Z9 1 U1 0 U2 7 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0741-0395 J9 GENET EPIDEMIOL JI Genet. Epidemiol. PD APR PY 2012 VL 36 IS 3 BP 206 EP 213 DI 10.1002/gepi.21613 PG 8 WC Genetics & Heredity; Mathematical & Computational Biology SC Genetics & Heredity; Mathematical & Computational Biology GA 932VX UT WOS:000303319700004 PM 22311237 ER PT J AU Zheng, G Wu, CO Kwak, M Jiang, W Joo, J Lima, JAC AF Zheng, Gang Wu, Colin O. Kwak, Minjung Jiang, Wenhua Joo, Jungnam Lima, Joao A. C. TI Joint Analysis of Binary and Quantitative Traits With Data Sharing and Outcome-Dependent Sampling SO GENETIC EPIDEMIOLOGY LA English DT Article DE case-control; continuous trait; F-test; missing data; Fisher's combination; genome-wide ranking; polygenetic pleiotropy; scaled chi-squared distribution; trend test ID RHEUMATOID-ARTHRITIS; LINKAGE DISEQUILIBRIUM; P-VALUES; ASSOCIATION; ANTIBODIES; TESTS; SIZE; LOCI AB We study the analysis of a joint association between a genetic marker with both binary (case-control) and quantitative (continuous) traits, where the quantitative trait values are only available for the cases due to data sharing and outcome-dependent sampling. Data sharing becomes common in genetic association studies, and the outcome-dependent sampling is the consequence of data sharing, under which a phenotype of interest is not measured for some subgroup. The trend test (or Pearson's test) and F-test are often, respectively, used to analyze the binary and quantitative traits. Because of the outcome-dependent sampling, the usual F-test can be applied using the subgroup with the observed quantitative traits. We propose a modified F-test by also incorporating the genotype frequencies of the subgroup whose traits are not observed. Further, a combination of this modified F-test and Pearson's test is proposed by Fisher's combination of their P-values as a joint analysis. Because of the correlation of the two analyses, we propose to use a Gamma (scaled chi-squared) distribution to fit the asymptotic null distribution for the joint analysis. The proposed modified F-test and the joint analysis can also be applied to test single trait association (either binary or quantitative trait). Through simulations, we identify the situations under which the proposed tests are more powerful than the existing ones. Application to a real dataset of rheumatoid arthritis is presented. Genet. Epidemiol. 36:263-273, 2012. (C) 2012 Wiley Periodicals, Inc. C1 [Zheng, Gang] NHLBI, Off Biostat Res, Bethesda, MD 20892 USA. [Jiang, Wenhua; Lima, Joao A. C.] Johns Hopkins Univ, Sch Med, Baltimore, MD USA. [Joo, Jungnam] Natl Canc Ctr, Geonggi Do, South Korea. RP Zheng, G (reprint author), NHLBI, Off Biostat Res, 6701 Rockledge Dr, Bethesda, MD 20892 USA. EM zhengg@nhlbi.nih.gov FU National Institutes of Health [NO1-AR-2-2263, RO1-AR-44422]; National Arthritis Foundation FX This work is based on the data (GAW16) that were gathered with the support of grants from the National Institutes of Health (NO1-AR-2-2263 and RO1-AR-44422, Peter K. Gregersen, PI), and the National Arthritis Foundation. The use of the data was approved by GAW16. The authors would like to thank Neal Jeffries for extracting some marker data from GAW16 that were used in the application and Jing Qin for some helpful discussion. We also thank three reviewers for their insightful thoughts and helpful suggestions that led to the current version. The authors have no conflict of interest to declare. NR 20 TC 12 Z9 12 U1 0 U2 2 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0741-0395 J9 GENET EPIDEMIOL JI Genet. Epidemiol. PD APR PY 2012 VL 36 IS 3 BP 263 EP 273 DI 10.1002/gepi.21619 PG 11 WC Genetics & Heredity; Mathematical & Computational Biology SC Genetics & Heredity; Mathematical & Computational Biology GA 932VX UT WOS:000303319700010 PM 22460626 ER PT J AU Ward, JM Rehg, JE Morse, HC AF Ward, Jerrold M. Rehg, Jerold E. Morse, Herbert C., III TI Differentiation of Rodent Immune and Hematopoietic System Reactive Lesions from Neoplasias SO TOXICOLOGIC PATHOLOGY LA English DT Article DE clonality; mice; hematopoietic system; immune system; immunohistochemistry; lymph nodes; lymphoid; lymphoid hyperplasia; lymphoma; lymphoproliferative disease; rats; spleen; Thymus ID PLASMA-CELL NEOPLASMS; LYMPH-NODES; B-CELL; ENHANCED HISTOPATHOLOGY; IMMUNODEFICIENCY SYNDROME; EXTENDED HISTOPATHOLOGY; BETHESDA PROPOSALS; C-MYC; MICE; MOUSE AB The immune and hematopoietic systems play an important role in the normal homeostasis of blood and blood cells and for immune responses to endogenous and exogenous processes and insults. In order to interpret histopathologic changes in the immune and hematopoietic systems, it is important to understand the normal anatomy and histology of the thymus, spleen, lymph nodes, bone marrow, and other tissues. The thymus, spleen, and lymph nodes can be categorized by anatomical compartments, each of which contributes to specific immune functions. Lesions may be diagnosed by interpretive or descriptive (semiquantitative) methods. The interpretation of these tissues by lesion in anatomical compartments should allow for better understanding of these reactions and more definitive pathologic findings. Proliferative lesions may be difficult to differentiate from lymphomas and leukemias. The use of immunohistochemistry, compartmental pathology, and methods for the evaluation of clonality will make interpretation easier. C1 [Ward, Jerrold M.; Morse, Herbert C., III] NIAID, Immunopathol Lab, NIH, Bethesda, MD 20892 USA. [Rehg, Jerold E.] St Jude Childrens Hosp, Dept Pathol, Memphis, TN 38105 USA. [Ward, Jerrold M.] Global VetPathol, Bethesda, MD USA. RP Ward, JM (reprint author), NIAID, Immunopathol Lab, NIH, MSC 8152, Bethesda, MD 20892 USA. EM globalvetpathology@gmail.com OI Morse, Herbert/0000-0002-9331-3705 FU NIH, National Institute of Allergy and Infectious Diseases FX The authors disclosed receipt of the following financial support for the research, authorship, and/or publication of this article: in part, by the Intramural Research Program of the NIH, National Institute of Allergy and Infectious Diseases. NR 62 TC 8 Z9 8 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 APR PY 2012 VL 40 IS 3 BP 425 EP 434 DI 10.1177/0192623311431467 PG 10 WC Pathology; Toxicology SC Pathology; Toxicology GA 961JS UT WOS:000305461300002 PM 22215512 ER PT J AU Morgan, DL Jokinen, MP Price, HC Gwinn, WM Palmer, SM Flake, GP AF Morgan, Daniel L. Jokinen, Micheal P. Price, Herman C. Gwinn, William M. Palmer, Scott M. Flake, Gordon P. TI Bronchial and Bronchiolar Fibrosis in Rats Exposed to 2,3-Pentanedione Vapors: Implications for Bronchiolitis Obliterans in Humans SO TOXICOLOGIC PATHOLOGY LA English DT Article DE 2,3-pentanedione; bronchiolitis obliterans; acetyl propionyl; butter flavoring; diacetyl; nasal cavity; airways; rats; mice ID C-REACTIVE PROTEIN; ONCOSTATIN-M; LUNG TRANSPLANTATION; DERMAL FIBROBLASTS; EXPRESSION; DIACETYL; COLLAGEN; ALPHA; IDENTIFICATION; EPITHELIUM AB 2,3-Pentanedione (PD) is a component of artificial butter flavorings. The use of PD is increasing since diacetyl, a major butter flavorant, was associated with bronchiolitis obliterans (BO) in workers and has been removed from many products. Because the toxicity of inhaled PD is unknown, these studies were conducted to characterize the toxicity of inhaled PD across a range of concentrations in rodents. Male and female Wistar-Han rats and B6C3F1 mice were exposed to 0, 50, 100, or 200 ppm PD 6 h/d, 5 d/wk for up to 2 wk. Bronchoalveolar lavage fluid (BALF) was collected after 1, 3, 5, and 10 exposures, and histopathology was evaluated after 12 exposures. MCP-1, MCP-3, CRP, FGF-9, fibrinogen, and OSM were increased 2- to 9-fold in BALF of rats exposed for 5 and 10 days to 200 ppm. In mice, only fibrinogen was increased after 5 exposures to 200 ppm. The epithelium lining the respiratory tract was the site of toxicity in all mice and rats exposed to 200 ppm. Significantly, PD also caused both intraluminal and intramural fibrotic airway lesions in rats. The histopathological and biological changes observed in rats raise concerns that PD inhalation may cause BO in exposed humans. C1 [Morgan, Daniel L.; Gwinn, William M.; Flake, Gordon P.] Natl Inst Environm Hlth Sci, Natl Toxicol Program, Res Triangle Pk, NC 27709 USA. [Jokinen, Micheal P.] Charles River Labs Pathol Associates, Durham, NC USA. [Price, Herman C.] Alion Sci & Technol, Res Triangle Pk, NC USA. [Palmer, Scott M.] Duke Univ, Med Ctr, Durham, NC USA. RP Morgan, DL (reprint author), Natl Inst Environm Hlth Sci, Natl Toxicol Program, Mail Drop IF-00, Res Triangle Pk, NC 27709 USA. EM morgan3@niehs.nih.gov NR 42 TC 25 Z9 25 U1 0 U2 3 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 0192-6233 EI 1533-1601 J9 TOXICOL PATHOL JI Toxicol. Pathol. PD APR PY 2012 VL 40 IS 3 BP 448 EP 465 DI 10.1177/0192623311431946 PG 18 WC Pathology; Toxicology SC Pathology; Toxicology GA 961JS UT WOS:000305461300004 PM 22215510 ER PT J AU Ellis, JM Paul, DS DePetrillo, MA Singh, BP Malarkey, DE Coleman, RA AF Ellis, Jessica M. Paul, David S. DePetrillo, Michael A. Singh, Bhanu P. Malarkey, David E. Coleman, Rosalind A. TI Mice Deficient in Glycerol-3-Phosphate Acyltransferase-1 Have a Reduced Susceptibility to Liver Cancer SO TOXICOLOGIC PATHOLOGY LA English DT Article DE hepatocellular carcinoma; glycerolipid synthesis; non-alcoholic fatty liver disease; non-alcoholic steatohepatitis; diethylnitrosamine ID HEPATOCELLULAR-CARCINOMA; HEPATIC STEATOSIS; PPAR-ALPHA; NONALCOHOLIC STEATOHEPATITIS; TRIACYLGLYCEROL SYNTHESIS; PEROXISOME PROLIFERATOR; INSULIN-RESISTANCE; HEPATOCARCINOGENESIS; MITOCHONDRIAL; IDENTIFICATION AB The risk of hepatocellular carcinoma increases with the persistence of non-alcoholic fatty liver disease. Triacylglycerol synthesis is initiated by glycerol-3-phosphate acyltransferase (GPAT). Of four isoforms, GPAT1 contributes 30-50% of total liver GPAT activity, and we hypothesized that it might influence liver susceptibility to tumorigenesis. C57Bl/6 mice deficient in GPAT1 were backcrossed 6 times to C3H mice. After exposure to the carcinogen diethylnitrosamine (DEN) and the tumor promoter phenobarbital, male Gpat1(-/-) mice, compared with controls (Gpat1(+/+)), had 93% fewer macroscopically visible nodules per liver at 21 weeks of age and 39% fewer at 34 weeks of age. Microscopically, control mice had increased numbers of foci of altered hepatocytes, particularly the basophilic subtype, as well as more, and malignant, liver neoplasms than did the Gpat1(-/-) mice. At 21 weeks of age, 50% (4/8) of control mice (50%) had hepatocellular adenomas with an average multiplicity (tumors per tumor-bearing-animal) of 4.3, while none occurred in 8 Gpat1(-/-) mice. At 34 weeks of age, all 15 control mice (100%) had hepatocellular adenomas with an average multiplicity of 5.2 compared to an incidence of 93% in Gpat1(-/-) mice and multiplicity of 3.1. HCCs were observed in 13% of control mice and in only 6% of Gpat1(-/-) mice. These data show that alterations in the formation of complex lipids catalyzed by Gpat1 reduce susceptibility to DEN-induced liver tumorigenesis. C1 [Ellis, Jessica M.; Paul, David S.; DePetrillo, Michael A.; Coleman, Rosalind A.] Univ N Carolina, Dept Nutr, Chapel Hill, NC 27599 USA. [Ellis, Jessica M.] Johns Hopkins Univ, Sch Med, Ctr Metab & Obes Res, Dept Biol Chem, Baltimore, MD USA. [Singh, Bhanu P.; Malarkey, David E.] Natl Inst Environm Hlth & Sci, Natl Toxicol Program, Cellular & Mol Pathol Branch, Res Triangle Pk, NC USA. [Singh, Bhanu P.] Dupont Haskell Global Ctr Hlth & Environm Sci, Newark, DE USA. RP Coleman, RA (reprint author), Univ N Carolina, Dept Nutr, CB 7461, Chapel Hill, NC 27599 USA. EM rcoleman@unc.edu FU NIH [DK056598]; predoctoral training grant in Integrative Vascular Biology [HL069768]; American Heart Association-Mid-Atlantic Region [P30 DK034987, P30-ES010126, P30 DK056350]; NIH, National Institute of Environmental Health Sciences FX This work was supported by NIH grant DK056598 (RAC); a predoctoral training grant HL069768 in Integrative Vascular Biology (JME); P30 DK034987, P30-ES010126, P30 DK056350, and a predoctoral fellowship from the American Heart Association-Mid-Atlantic Region (JME). This research was also supported in part by the Intramural Research Program of the NIH, National Institute of Environmental Health Sciences. NR 46 TC 2 Z9 3 U1 0 U2 4 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 APR PY 2012 VL 40 IS 3 BP 513 EP 521 DI 10.1177/0192623311432298 PG 9 WC Pathology; Toxicology SC Pathology; Toxicology GA 961JS UT WOS:000305461300010 PM 22215515 ER PT J AU Lipsky, LM Cheon, K Nansel, TR Albert, PS AF Lipsky, Leah M. Cheon, Kyeongmi Nansel, Tonja R. Albert, Paul S. TI Candidate measures of whole plant food intake are related to biomarkers of nutrition and health in the US population (National Health and Nutrition Examination Survey 1999-2002) SO NUTRITION RESEARCH LA English DT Article DE Human; Nutrition indices; National Health and Nutrition Examination Survey; Food plants; Biomarkers ID CORONARY-HEART-DISEASE; CARDIOVASCULAR-DISEASE; DIETARY PATTERNS; VEGETABLE INTAKE; RISK-FACTORS; GRAIN INTAKE; CANCER; WOMEN; QUALITY; ADULTS AB Indices of overall dietary patterns are used in epidemiologic research to examine the relationship between nutrition and health. The objective of this study was to develop and validate an interpretable summary measure of dietary intake of whole plant foods (WPF; whole grains, vegetables, whole fruit, legumes, nuts, seeds) because of their similar nutritional characteristics and health effects. Six candidate WPF measures were calculated using data from subjects (age >= 6 years) participating in the 1999-2000 and 2001-2002 National Health and Nutrition Examination Survey. Measures differed by the inclusion or exclusion of potatoes and whether they were expressed as total intake or as a proportion of energy (4180 kJ) or mass (kg) consumed. Both standard and nontruncated (allowed to vary proportionally with intake) Healthy Eating Index-2005 (HEI-2005) scores were calculated. Regression analysis examined the associations between WPF and HEI-2005 measures, and between all diet measures and serum carotenoid concentration, serum lipids, fasting glucose, insulin, C-peptide, and C-reactive protein. Mean total WPF intake was 3.6 cup/oz equivalents, or 1.7 cup/oz equivalents per 4180 kJ and per kg. The largest R-2 between WPF and HEI-2005 measures was found for energy-adjusted WPF including potatoes and nontruncated HEI-2005 (R-2 = 0.50). All diet measures were positively related to serum carotenoids (P <.001) and were similarly related to health indicators (R-2 range from 0.003 to 0.16, P <.045 for regressions, indicating significant associations between WPF measures and health indicators). Whole plant food measures are interpretable indicators of dietary intake that are significantly related to nutrition and health biomarkers and may be of public health use. Published by Elsevier Inc. C1 [Lipsky, Leah M.; Cheon, Kyeongmi; Nansel, Tonja R.; Albert, Paul S.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Bethesda, MD 20852 USA. RP Lipsky, LM (reprint author), Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Bethesda, MD 20852 USA. EM lipskylm@mail.nih.gov OI Nansel, Tonja/0000-0002-8298-7595; Lipsky, Leah/0000-0003-2645-4388 FU Eunice Kennedy Shriver National Institute of Child Health and Human Development FX This research was funded by the intramural research program of the Eunice Kennedy Shriver National Institute of Child Health and Human Development. The authors declare no conflicts of interest. NR 37 TC 11 Z9 11 U1 0 U2 19 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0271-5317 J9 NUTR RES JI Nutr. Res. PD APR PY 2012 VL 32 IS 4 BP 251 EP 259 DI 10.1016/j.nutres.2012.03.005 PG 9 WC Nutrition & Dietetics SC Nutrition & Dietetics GA 958TS UT WOS:000305264200003 PM 22575037 ER PT J AU Kong, A Beresford, SAA Imayama, I Duggan, C Alfano, CM Foster-Schubert, KE Neuhouser, ML Johnson, DB Wang, CY Xiao, LR Bain, CE McTiernan, A AF Kong, Angela Beresford, Shirley A. A. Imayama, Ikuyo Duggan, Catherine Alfano, Catherine M. Foster-Schubert, Karen E. Neuhouser, Marian L. Johnson, Donna B. Wang, Ching-Yun Xiao, Liren Bain, Carolyn E. McTiernan, Anne TI Adoption of diet-related self-monitoring behaviors varies by race/ethnicity, education, and baseline binge eating score among overweight-to-obese postmenopausal women in a 12-month dietary weight loss intervention SO NUTRITION RESEARCH LA English DT Article ID LOSS MAINTENANCE; RISK-FACTOR; TRIAL; QUESTIONNAIRE; LIFE; PARTICIPANTS; PREVENTION; PROGRAM; GAIN; MEN AB Recent research has identified self-monitoring behaviors as important strategies for both initial weight loss and weight loss maintenance, but relatively little is known about adopters and nonadopters of these behaviors. To test our hypothesis that key characteristics distinguish adopters from nonadopters, we examined the demographic characteristics and eating behaviors (eg, restrained, uncontrolled, emotional, and binge eating) associated with more frequent compared with less frequent use of these behaviors. Baseline demographic characteristics and eating behaviors as well as 12-month self-monitoring behaviors (ie, self-weighing, food journaling, monitoring energy intake) were assessed in 123 postmenopausal women enrolled in a dietary weight loss intervention. Logistic regression models were used to test associations of self-monitoring use with demographic characteristics and eating behaviors. Nonwhites, compared with non-Hispanic whites, were less likely to monitor energy intake regularly (adjusted odds ratio [OR], 0.36; 95% confidence interval [CI], 0.13-0.97; P < .05), controlling for intervention arm and baseline body mass index. Participants with a college degree or higher education were less likely to self-weigh daily (adjusted OR, 0.30; 95% CI, 0.13-0.67; P < .01) compared with individuals who attended some college or less. Those with higher baseline binge eating scores were less likely to monitor energy intake (adjusted OR, 0.84; 95% CI, 0.73-0.97; P < .01) compared with participants with lower binge eating scores. In summary, use of diet-related self-monitoring behaviors varied by race/ethnicity, education, and binge eating score in postmenopausal women who completed a year-long dietary weight loss intervention. Improved recognition of groups less likely to self-monitor may be helpful in promoting these behaviors in future interventions. (C) 2012 Elsevier Inc. All rights reserved. C1 [Beresford, Shirley A. A.; Imayama, Ikuyo; Duggan, Catherine; Foster-Schubert, Karen E.; Neuhouser, Marian L.; Wang, Ching-Yun; Xiao, Liren; Bain, Carolyn E.; McTiernan, Anne] Fred Hutchinson Canc Res Ctr, Seattle, WA 98109 USA. [Beresford, Shirley A. A.; Neuhouser, Marian L.; Johnson, Donna B.; McTiernan, Anne] Univ Washington, Sch Publ Hlth, Seattle, WA 98195 USA. [Kong, Angela] Univ Illinois, Canc Educ & Career Dev Program, Chicago, IL 60608 USA. [Alfano, Catherine M.] NCI, Off Canc Survivorship, Bethesda, MD 20892 USA. [Foster-Schubert, Karen E.; McTiernan, Anne] Univ Washington, Sch Med, Seattle, WA 98195 USA. RP McTiernan, A (reprint author), Fred Hutchinson Canc Res Ctr, POB 19024,Mail Stop M4-B874, Seattle, WA 98109 USA. EM amctiem@fhcrc.org RI Duggan, Catherine/F-9414-2015 OI Duggan, Catherine/0000-0001-7369-4021 FU National Cancer Institute [R01 CA105204-01A1, R25 CA094880, 2R25CA057699, U54 CA116847]; National Center for Research Resources [5 KL2 RR025015-03] FX This study was supported by the National Cancer Institute (grants R01 CA105204-01A1, R25 CA094880, 2R25CA057699, and U54 CA116847) and National Center for Research Resources (grant 5 KL2 RR025015-03). NR 28 TC 5 Z9 5 U1 2 U2 17 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0271-5317 J9 NUTR RES JI Nutr. Res. PD APR PY 2012 VL 32 IS 4 BP 260 EP 265 DI 10.1016/j.nutres.2012.03.001 PG 6 WC Nutrition & Dietetics SC Nutrition & Dietetics GA 958TS UT WOS:000305264200004 PM 22575038 ER PT J AU Demple, B Rao, KS Bohr, VA AF Demple, Bruce Rao, Kalluri S. Bohr, Vilhelm A. TI Indo-US workshop on base excision DNA repair, brain function and aging Preface SO MECHANISMS OF AGEING AND DEVELOPMENT LA English DT Editorial Material ID MITOCHONDRIAL-DNA; DAMAGE C1 [Demple, Bruce] SUNY Stony Brook, Dept Pharmacol Sci, Sch Med, Stony Brook, NY 11790 USA. [Rao, Kalluri S.] Jawaharlal Nehru Technol Univ, Inst Sci & Technol, Biotechnol Res Ctr, Hyderabad 500085, Andhra Pradesh, India. [Rao, Kalluri S.] Jawaharlal Nehru Technol Univ, Inst Sci & Technol, Ctr Innovat Res, Hyderabad 500085, Andhra Pradesh, India. [Bohr, Vilhelm A.] NIA, Lab Mol Gerontol, NIH, Baltimore, MD 21224 USA. RP Demple, B (reprint author), SUNY Stony Brook, Dept Pharmacol Sci, Sch Med, Stony Brook, NY 11790 USA. FU Intramural NIH HHS [Z99 AG999999] NR 11 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0047-6374 J9 MECH AGEING DEV JI Mech. Ageing Dev. PD APR PY 2012 VL 133 IS 4 SI SI BP V EP VI DI 10.1016/S0047-6374(12)00063-2 PG 2 WC Cell Biology; Geriatrics & Gerontology SC Cell Biology; Geriatrics & Gerontology GA 953TE UT WOS:000304895300001 PM 22579128 ER PT J AU Sykora, P Wilson, DM Bohr, VA AF Sykora, Peter Wilson, David M., III Bohr, Vilhelm A. TI Repair of persistent strand breaks in the mitochondrial genome SO MECHANISMS OF AGEING AND DEVELOPMENT LA English DT Article; Proceedings Paper CT Indo-US Workshop on Base Excision DNA Repair, Brain Function and Aging CY JAN, 2011 CL Hyderabad, INDIA DE DNA repair; Mitochondria; Aging; Oxidative DNA damage ID BASE EXCISION-REPAIR; DNA-LIGASE-III; ONSET SPINOCEREBELLAR ATAXIA; DISEASE PROTEIN APRATAXIN; MAMMALIAN MITOCHONDRIA; OXIDATIVE STRESS; GENETIC-DISEASE; XRCC1; MUTATIONS; DAMAGE AB Oxidative DNA damage has been attributed to increased cancer incidence and premature aging phenotypes. Reactive oxygen species (ROS) are unavoidable byproducts of oxidative phosphorylation and are the major contributors of endogenous oxidative damage. To prevent the negative effects of ROS, cells have developed DNA repair mechanisms designed to specifically combat endogenous DNA modifications. The base excision repair (BER) pathway is primarily responsible for the repair of small non-helix distorting lesions and DNA single strand breaks. This repair pathway is found in all organisms, and in mammalian cells, consists of three related sub-pathways: short patch (SP-BER), long patch (LP-BER) and single strand break repair (SSBR). While much is known about nuclear BER, comparatively little is known about this pathway in the mitochondria, particularly the LP-BER and SSBR sub-pathways. There are a number of proteins that have recently been found to be involved in mitochondrial BER, including Cockayne syndrome proteins A and B (CSA and CSB), aprataxin (APTX), tryosyl-DNA phosphodiesterase 1 (TDP1), flap endonuclease 1 (FEN-1) and exonuclease G (EXOG). These significant advances in mitochondrial DNA repair may open new avenues in the management and treatment of a number of neurological disorders associated with mitochondrial dysfunction, and will be reviewed in further detail herein. (C) 2011 Published by Elsevier Ireland Ltd. C1 [Sykora, Peter; Wilson, David M., III; Bohr, Vilhelm A.] NIH, Biomed Res Ctr, Baltimore, MD 21224 USA. RP Bohr, VA (reprint author), NIH, Biomed Res Ctr, 251 Bayview Blvd, Baltimore, MD 21224 USA. EM sykorap@mail.nih.gov; wilsonda@mail.nih.gov; BohrV@grc.nia.nih.gov FU Intramural NIH HHS [Z01 AG000733-12, ZIA AG000733-17] NR 63 TC 27 Z9 27 U1 1 U2 9 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0047-6374 J9 MECH AGEING DEV JI Mech. Ageing Dev. PD APR PY 2012 VL 133 IS 4 SI SI BP 169 EP 175 DI 10.1016/j.mad.2011.11.003 PG 7 WC Cell Biology; Geriatrics & Gerontology SC Cell Biology; Geriatrics & Gerontology GA 953TE UT WOS:000304895300010 PM 22138376 ER PT J AU Briggs, JW Ren, L Nguyen, R Chakrabarti, K Cassavaugh, J Rahim, S Bulut, G Zhou, M Veenstra, TD Chen, QR Wei, JS Khan, J Uren, A Khanna, C AF Briggs, Joseph W. Ren, Ling Nguyen, Rachel Chakrabarti, Kristi Cassavaugh, Jessica Rahim, Said Bulut, Gulay Zhou, Ming Veenstra, Timothy D. Chen, Qingrong Wei, Jun S. Khan, Javed Uren, Aykut Khanna, Chand TI The Ezrin Metastatic Phenotype Is Associated with the Initiation of Protein Translation SO NEOPLASIA LA English DT Article ID MESSENGER-RNA; EUKARYOTIC TRANSLATION; ERM PROTEINS; POLY(A)-BINDING PROTEIN-1; PLASMA-MEMBRANE; GENE-EXPRESSION; CELL CARCINOMA; OSTEOSARCOMA; CYTOSKELETON; RIBOSOME AB We previously associated the cytoskeleton linker protein, Ezrin, with the metastatic phenotype of pediatric sarcomas, including osteosarcoma and rhabdomyosarcoma. These studies have suggested that Ezrin contributes to the survival of cancer cells after their arrival at secondary metastatic locations. To better understand this role in metastasis, we undertook two noncandidate analyses of Ezrin function including a microarray subtraction of high- and low-Ezrin-expressing cells and a proteomic approach to identify proteins that bound the N-terminus of Ezrin in tumor lysates. Functional analyses of these data led to a novel and unifying hypothesis that Ezrin contributes to the efficiency of metastasis through regulation of protein translation. In support of this hypothesis, we found Ezrin to be part of the ribonucleoprotein complex to facilitate the expression of complex messenger RNA in cells and to bind with poly A binding protein 1 (PABP1; PABPC1). The relevance of these findings was supported by our identification of Ezrin and components of the translational machinery in pseudopodia of highly metastatic cells during the process of cell invasion. Finally, two small molecule inhibitors recently shown to inhibit the Ezrin metastatic phenotype disrupted the Ezrin/PABP1 association. Taken together, these results provide a novel mechanistic basis by which Ezrin may contribute to metastasis. C1 [Khanna, Chand] NCI, Tumor & Metastasis Biol Sect, Pediat Oncol Branch, Ctr Canc Res,NIH, Bethesda, MD 20892 USA. [Rahim, Said; Bulut, Gulay; Uren, Aykut] Georgetown Univ, Lombardi Canc Ctr, Washington, DC USA. [Zhou, Ming; Veenstra, Timothy D.] NCI, Lab Prote & Analyt Technol, Adv Technol Program, SAIC Frederick Inc, Frederick, MD 21701 USA. [Chen, Qingrong; Wei, Jun S.; Khan, Javed] NCI, Oncogen Sect, Pediat Oncol Branch, Ctr Canc Res, Bethesda, MD 20892 USA. RP Khanna, C (reprint author), NCI, Tumor & Metastasis Biol Sect, Pediat Oncol Branch, Ctr Canc Res,NIH, 37 Convent Dr,Rm 2144, Bethesda, MD 20892 USA. EM khannac@mail.nih.gov RI Khan, Javed/P-9157-2014 OI Khan, Javed/0000-0002-5858-0488 NR 56 TC 16 Z9 17 U1 0 U2 7 PU NEOPLASIA PRESS PI ANN ARBOR PA 1150 W MEDICAL CENTER DR, MSRB III, RM 9303, ANN ARBOR, MI 48109-0648 USA SN 1522-8002 J9 NEOPLASIA JI Neoplasia PD APR PY 2012 VL 14 IS 4 BP 297 EP + DI 10.1593/neo.111518 PG 16 WC Oncology SC Oncology GA 956EG UT WOS:000305072100004 PM 22577345 ER PT J AU Orru, CD Wilham, JM Vascellari, S Hughson, AG Caughey, B AF Orru, Christina D. Wilham, Jason M. Vascellari, Sarah Hughson, Andrew G. Caughey, Byron TI New generation QuIC assays for prion seeding activity SO PRION LA English DT Review DE real time QuIC; prion detection; enhanced QuIC; prion diagnosis; recombinant PMCA ID CREUTZFELDT-JAKOB-DISEASE; IN-VITRO AMPLIFICATION; MISFOLDING CYCLIC AMPLIFICATION; QUAKING-INDUCED CONVERSION; CHRONIC WASTING DISEASE; SEEDED CONVERSION; SENSITIVE ASSAY; PROTEIN; SCRAPIE; BLOOD AB The ability of abnormal TSE-associated forms of PrP to seed the formation of amyloid fibrils from recombinant PrPSen has served as the basis for several relatively rapid and highly sensitive tests for prion diseases. These tests include rPrP-PMCA (rPMCA), standard quaking-induced conversion (S-QuIC), amyloid seeding assay (ASA), real-time QuIC (RT-QuIC) and enhanced QuIC (eQuIC). Here, we summarize recent improvements in the RT-QuIC-based assays that enhance the practicality, sensitivity and quantitative attributes of assays QuIC and promote the detection of prion seeding activity in dilute, inhibitor-laden fluids such as blood plasma. C1 [Orru, Christina D.; Wilham, Jason M.; Vascellari, Sarah; Hughson, Andrew G.; Caughey, Byron] NIAID, Persistent Viral Dis Lab, Rocky Mt Labs, NIH, Hamilton, MT USA. RP Caughey, B (reprint author), NIAID, Persistent Viral Dis Lab, Rocky Mt Labs, NIH, Hamilton, MT USA. EM bcaughey@nih.gov FU NIAID, NIH; Master and Back Program of the Regione Sardegna (Italy) FX This work was supported by the Intramural Research Program of the NIAID, NIH. S.V. was partially supported by the Master and Back Program of the Regione Sardegna (Italy). NR 44 TC 28 Z9 28 U1 0 U2 10 PU LANDES BIOSCIENCE PI AUSTIN PA 1806 RIO GRANDE ST, AUSTIN, TX 78702 USA SN 1933-6896 J9 PRION JI Prion PD APR-JUN PY 2012 VL 6 IS 2 BP 147 EP 152 DI 10.4161/pri.19430 PG 6 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 948SW UT WOS:000304523900009 ER PT J AU Avila, C Huang, RJ Stevens, MV Aponte, AM Tripodi, D Kim, KY Sack, MN AF Avila, C. Huang, R. J. Stevens, M. V. Aponte, A. M. Tripodi, D. Kim, K. Y. Sack, M. N. TI Platelet Mitochondrial Dysfunction is Evident in Type 2 Diabetes in Association with Modifications of Mitochondrial Anti-Oxidant Stress Proteins SO EXPERIMENTAL AND CLINICAL ENDOCRINOLOGY & DIABETES LA English DT Article DE mitochondria; platelets; reactive oxygen species; respiration; diabetes ID SKELETAL-MUSCLE; INSULIN-RESISTANCE AB Objective: Mitochondrial dysfunction and oxidative stress in insulin responsive tissues is implicated in the pathogenesis of type 2 diabetes. Whether these perturbations extend to other tissues and contribute to their pathophysiology is less well established. The objective of this study was to investigate platelet mitochondria to evaluate whether type 2 diabetes associated mitochondria( dysfunction is evident in circulating cells. Method: A pilot study of mitochondrial respiratory function and proteomic changes comparing platelets extracted from insulin sensitive (n=8) and type 2 diabetic subjects (n=7). Results: In-situ platelet mitochondria show diminished oxygen consumption and lower oxygen-dependent ATP synthesis in diabetic vs. control subjects. Mass spectrometric identification and confirmatory immunoblot analysis identifies induction of the mitochondrial anti-oxidant enzymes superoxide dismutase 2 and thioredoxin-dependent peroxide reductase 3 in platelets of diabetic subjects. As oxidative stress upregulates anti-oxidant enzymes we assessed mitochondrial protein carbonylation as an index of oxidative-stress. Platelets of diabetic subjects exhibit significantly increased protein carbonylation compared to controls. Conclusions: As platelets are anuclear fragments of megakaryocytes, our data suggest that the bone marrow compartment in type 2 diabetic subjects is exposed to increased mitochondrial oxidative stress with upregulation of nuclear-encoded antioxidant mitochondrial enzymes. This 'stress-signature' in platelets of diabetic subjects is associated with a diminution of their mitochondrial contribution to energy production and support that mitochondrial perturbations in type 2 diabetes extends beyond the classical insulin responsive tissues. Platelets, as "accessible human tissue", may be useful to measure the mitochondrial modulatory effects of emerging anti-diabetic therapeutics. C1 [Avila, C.; Huang, R. J.; Stevens, M. V.; Tripodi, D.; Kim, K. Y.; Sack, M. N.] NHLBI, Ctr Mol Med, NIH, Bethesda, MD 20892 USA. [Aponte, A. M.] NHLBI, Prote Core Facil, NIH, Bethesda, MD 20892 USA. RP Sack, MN (reprint author), NHLBI, Ctr Mol Med, NIH, Bldg 10-CRC,Room 5-3150,10 Ctr Dr, Bethesda, MD 20892 USA. EM sackm@nhlbi.nih.gov FU Division of Intramural Research of the NHLBI; NIH-Pfizer FX This research is funded by the Division of Intramural Research of the NHLBI. CA and RJH were funded by an NIH-Pfizer Clinical Research Training Fellowship. We thank the NHLBI Flow Cytometry Core Facility for assistance in the confirmation of platelet purity and Stephanie A French, Darci Phillips and Dr. Marjan Gucek of the NHLBI for helpful discussion regarding mitochondrial protein isolation and proteomic analysis. NR 15 TC 25 Z9 25 U1 2 U2 16 PU JOHANN AMBROSIUS BARTH VERLAG MEDIZINVERLAGE HEIDELBERG GMBH PI STUTTGART PA RUEDIGERSTR 14, D-70469 STUTTGART, GERMANY SN 0947-7349 J9 EXP CLIN ENDOCR DIAB JI Exp. Clin. Endocrinol. Diabet. PD APR PY 2012 VL 120 IS 4 BP 248 EP 251 DI 10.1055/s-0031-1285833 PG 4 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 949NI UT WOS:000304582500020 PM 21922457 ER PT J AU Felsenfeld, G Dekker, J AF Felsenfeld, Gary Dekker, Job TI Genome architecture and expression SO CURRENT OPINION IN GENETICS & DEVELOPMENT LA English DT Editorial Material C1 [Felsenfeld, Gary] NIDDK, Chem Phys Sect, Mol Biol Lab, NIH, Bethesda, MD 20892 USA. [Dekker, Job] Univ Massachusetts, Sch Med, LRB 509, Worcester, MA 01605 USA. RP Felsenfeld, G (reprint author), NIDDK, Chem Phys Sect, Mol Biol Lab, NIH, Bldg 5,Room 212,5 Mem Dr, Bethesda, MD 20892 USA. EM garyf@intra.niddk.nih.gov FU Intramural NIH HHS; NHGRI NIH HHS [R01 HG003143] NR 0 TC 6 Z9 6 U1 2 U2 9 PU CURRENT BIOLOGY LTD PI LONDON PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND SN 0959-437X J9 CURR OPIN GENET DEV JI Curr. Opin. Genet. Dev. PD APR PY 2012 VL 22 IS 2 BP 59 EP 61 DI 10.1016/j.gde.2012.03.003 PG 3 WC Cell Biology; Genetics & Heredity SC Cell Biology; Genetics & Heredity GA 946FX UT WOS:000304338000001 PM 22483506 ER PT J AU Krivega, I Dean, A AF Krivega, Ivan Dean, Ann TI Enhancer and promoter interactions-long distance calls SO CURRENT OPINION IN GENETICS & DEVELOPMENT LA English DT Review ID BETA-GLOBIN LOCUS; RNA-POLYMERASE-II; MAJOR HISTOCOMPATIBILITY COMPLEX; CCCTC-BINDING FACTOR; GENE-EXPRESSION; CONTROL REGION; NONCODING RNAS; ERYTHROID-DIFFERENTIATION; INTERGENIC TRANSCRIPTION; CHROMATIN ARCHITECTURE AB In metazoans, enhancers of gene transcription must often exert their effects over tens of kilobases of DNA. Over the past decade it has become clear that to do this, enhancers come into close proximity with target promoters with the looping away of intervening sequences. In a few cases proteins that are involved in the establishment or maintenance of these loops have been revealed but how the proper gene target is selected remains mysterious. Chromatin insulators had been appreciated as elements that play a role in enhancer fidelity through their enhancer blocking or barrier activity. However, recent work suggests more direct participation of insulators in enhancer-gene interactions. The emerging view begins to incorporate transcription activation by distant enhancers with large scale nuclear architecture and subnuclear movement. C1 [Krivega, Ivan; Dean, Ann] NIDDK, Cellular & Dev Biol Lab, NIH, Bethesda, MD 20982 USA. RP Dean, A (reprint author), NIDDK, Cellular & Dev Biol Lab, NIH, Bethesda, MD 20982 USA. EM anndean@helix.nih.gov RI Krivega, Ivan/G-9247-2015 OI Krivega, Ivan/0000-0002-3473-4198 FU NIDDK, NIH FX We would like to thank Dr. Gerd Blobel for helpful comments on the manuscript and members of our laboratory for their suggestions. Work in our laboratory is supported by the Intramural Program of NIDDK, NIH. NR 64 TC 75 Z9 76 U1 1 U2 19 PU CURRENT BIOLOGY LTD PI LONDON PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND SN 0959-437X J9 CURR OPIN GENET DEV JI Curr. Opin. Genet. Dev. PD APR PY 2012 VL 22 IS 2 BP 79 EP 85 DI 10.1016/j.gde.2011.11.001 PG 7 WC Cell Biology; Genetics & Heredity SC Cell Biology; Genetics & Heredity GA 946FX UT WOS:000304338000004 PM 22169023 ER PT J AU Reyes-Turcu, FE Grewal, SIS AF Reyes-Turcu, Francisca E. Grewal, Shiv I. S. TI Different means, same end - heterochromatin formation by RNAi and RNAi-independent RNA processing factors in fission yeast SO CURRENT OPINION IN GENETICS & DEVELOPMENT LA English DT Review ID LONG NONCODING RNAS; HISTONE H3; HP1 PROTEINS; SCHIZOSACCHAROMYCES-POMBE; SELECTIVE ELIMINATION; LYSINE-9 METHYLATION; CHROMODOMAIN PROTEIN; EPIGENETIC CONTROL; CHP1 CHROMODOMAIN; UBIQUITIN LIGASE AB The assembly of heterochromatin in eukaryotic genomes is critical for diverse chromosomal events including regulation of gene expression, silencing of repetitive DNA elements, proper segregation of chromosomes and maintenance of genomic integrity. Previous studies have shown that noncoding RNAs and the RNA interference (RNAi) machinery promote the assembly of heterochromatin that serves as a multipurpose platform for targeting effectors involved in various chromosomal processes. Recent work has revealed that RNAi-independent mechanisms, involving RNA processing activities that utilize both noncoding and coding RNAs, operate in the assembly of heterochromatin. These findings have established that, in addition to coding for proteins, mRNAs also function as signaling molecules that modify chromatin structure by targeting heterochromatin assembly factors. C1 [Reyes-Turcu, Francisca E.; Grewal, Shiv I. S.] NCI, Biochem & Mol Biol Lab, NIH, Bethesda, MD 20892 USA. RP Grewal, SIS (reprint author), NCI, Biochem & Mol Biol Lab, NIH, Bethesda, MD 20892 USA. EM grewals@mail.nih.gov FU National Institutes of Health, National Cancer Institute FX We thank members of Grewal Laboratory for helpful discussions. We are especially thankful to J. Barrowman, V. Chalamcharla and N. Lee comments on the manuscript. Research in Grewal Laboratory is supported by the Intramural Research Program of the National Institutes of Health, National Cancer Institute. NR 75 TC 39 Z9 41 U1 1 U2 16 PU CURRENT BIOLOGY LTD PI LONDON PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND SN 0959-437X J9 CURR OPIN GENET DEV JI Curr. Opin. Genet. Dev. PD APR PY 2012 VL 22 IS 2 BP 156 EP 163 DI 10.1016/j.gde.2011.12.004 PG 8 WC Cell Biology; Genetics & Heredity SC Cell Biology; Genetics & Heredity GA 946FX UT WOS:000304338000014 PM 22243696 ER PT J AU Semba, RD Chang, SS Sun, K Talegawkar, S Ferrucci, L Fried, LP AF Semba, R. D. Chang, S. S. Sun, K. Talegawkar, S. Ferrucci, L. Fried, L. P. TI Serum carotenoids and pulmonary function in older community-dwelling women SO JOURNAL OF NUTRITION HEALTH & AGING LA English DT Article DE Aging; carotenoids; lung function; women ID LUNG-FUNCTION; BETA-CAROTENE; GENERAL-POPULATION; ALPHA-TOCOPHEROL; DIETARY PATTERNS; VITAMIN-A; DISEASE; HEALTH; NUTRITION; FRUITS AB Deterioration in pulmonary function is associated with greater disability and mortality in older adults. Dietary antioxidants are implicated in lung health, but the relationship between major dietary antioxidants, such as serum carotenoids, and pulmonary function have not been well characterized. Serum carotenoids are considered the most reliable indicator of fruit and vegetable intake. We examined the relationship between serum alpha-carotene, beta-carotene, beta-cryptoxanthin, lutein/zeaxanthin, and lycopene with pulmonary function (forced expiratory volume in one second [FEV1] and forced vital capacity [FVC]) in a population-based sample of 631 moderately to severely disabled community-dwelling older women (Women's Health and Aging Study I) in Baltimore, Maryland, USA. Higher serum alpha-carotene and beta-carotene concentrations were positively associated with both FEV1 and FVC, respectively (all P < 0.05), in separate multivariate linear regression models adjusting for age, race, education, cognition, anemia, inflammation, and chronic diseases. Total serum carotenoids were associated with FEV1 (P = 0.08) and FVC (P = 0.06), respectively, in similar models. No association was found between beta-cryptoxanthin, lutein/zeaxanthin, and lycopene, and FEV1 or FVC. Higher serum alpha-carotene and beta-carotene concentrations, which reflect greater intake of orange and dark green leafy fruits and vegetables, were associated with better pulmonary function among older community-dwelling women.function may lead to food avoidance and to a higher incidence of digestive complaints. C1 [Semba, R. D.] Johns Hopkins Univ, Sch Med, Dept Ophthalmol, Baltimore, MD 21287 USA. [Sun, K.] Yale Univ, Sch Med, Dept Internal Med, Sect Geriatr, New Haven, CT 06510 USA. [Talegawkar, S.] Johns Hopkins Bloomberg Sch Publ Hlth, Dept Int Hlth, Ctr Human Nutr, Baltimore, MD USA. [Ferrucci, L.] NIA, Longitudinal Studies Sect, Clin Res Branch, NIH, Baltimore, MD 21224 USA. [Fried, L. P.] Columbia Univ, Mailman Sch Publ Hlth, New York, NY USA. RP Semba, RD (reprint author), Johns Hopkins Univ, Sch Med, Dept Ophthalmol, Smith Bldg,M015,400 N Broadway, Baltimore, MD 21287 USA. EM rdsemba@jhmi.edu FU National Institute on Aging [R01 AG027012]; NIH-NCRR; OPD-GCRC [RR00722]; NIA [N01-AG12112]; Johns Hopkins Older Americans' Independence Center; National Institute on Aging, NIH FX Grant Support: This work was supported by National Institute on Aging Grant R01 AG027012, NIH-NCRR, OPD-GCRC grant RR00722, and NIA Contract N01-AG12112, the Johns Hopkins Older Americans' Independence Center, and the Intramural Research Program, National Institute on Aging, NIH. NR 33 TC 3 Z9 3 U1 0 U2 3 PU SPRINGER FRANCE PI PARIS PA 22 RUE DE PALESTRO, PARIS, 75002, FRANCE SN 1279-7707 J9 J NUTR HEALTH AGING JI J. Nutr. Health Aging PD APR PY 2012 VL 16 IS 4 BP 291 EP 296 DI 10.1007/s12603-012-0034-z PG 6 WC Geriatrics & Gerontology; Nutrition & Dietetics SC Geriatrics & Gerontology; Nutrition & Dietetics GA 943OT UT WOS:000304134500003 PM 22499445 ER PT J AU Caughey, B Orru, CD Wilham, JM Vascellari, S Hughson, AG Raymond, LD Raymond, GJ AF Caughey, Byron Orru, Christina D. Wilham, Jason M. Vascellari, Sarah Hughson, Andrew G. Raymond, Lynne D. Raymond, Gregory J. TI Prion-seeded conversion of recombinant PrP: implications for prion biology and diagnostics SO PRION LA English DT Meeting Abstract ID CEREBROSPINAL-FLUID C1 [Caughey, Byron; Orru, Christina D.; Wilham, Jason M.; Vascellari, Sarah; Hughson, Andrew G.; Raymond, Lynne D.; Raymond, Gregory J.] NIAID, Rocky Mt Labs, NIH, Hamilton, MT 59840 USA. NR 7 TC 0 Z9 0 U1 0 U2 4 PU LANDES BIOSCIENCE PI AUSTIN PA 1806 RIO GRANDE ST, AUSTIN, TX 78702 USA SN 1933-6896 J9 PRION JI Prion PD APR-JUN PY 2012 VL 6 SU S BP 11 EP 12 PG 2 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 944WK UT WOS:000304234300024 ER PT J AU Blanco, RA De Wolf, C Tan, B Agarwal, S Orru, C Caughey, B Raeber, A Gill, A Manson, J McCutcheon, S AF Blanco, Richard Alejo De Wolf, Christopher Tan, Boon Agarwal, Sonya Orru, Christina Caughey, Byron Raeber, Alex Gill, Andrew Manson, Jean McCutcheon, Sandra TI Analysis of BSE-infected sheep tissues and plasma using the real-time quaking induced conversion (RT-QuIC) assay SO PRION LA English DT Meeting Abstract C1 [Blanco, Richard Alejo; De Wolf, Christopher; Tan, Boon; Agarwal, Sonya; Gill, Andrew; Manson, Jean; McCutcheon, Sandra] Roslin Inst, Edinburgh, Midlothian, Scotland. [Blanco, Richard Alejo; De Wolf, Christopher; Tan, Boon; Agarwal, Sonya; Gill, Andrew; Manson, Jean; McCutcheon, Sandra] R D SVS, Edinburgh, Midlothian, Scotland. [Orru, Christina; Caughey, Byron] NIAID, NIH, Hamilton, MT USA. [Raeber, Alex] Prionics AG, Zurich, Switzerland. RI Gill, Andrew/A-5219-2009 NR 5 TC 2 Z9 2 U1 0 U2 2 PU LANDES BIOSCIENCE PI AUSTIN PA 1806 RIO GRANDE ST, AUSTIN, TX 78702 USA SN 1933-6896 J9 PRION JI Prion PD APR-JUN PY 2012 VL 6 SU S BP 94 EP 94 PG 1 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 944WK UT WOS:000304234300194 ER PT J AU Pick, CG Rubovitch, V Rachmany, L Tweedie, D Hoffer, BJ Schreiber, S Greig, NH AF Pick, Chaim G. (Chagi) Rubovitch, Vardit Rachmany, Lital Tweedie, David Hoffer, Barry J. Schreiber, Shaul Greig, Nigel H. TI Possible translational study to the clinic of a combat zone-like mouse model of Blast Brain Injury SO BRAIN INJURY LA English DT Meeting Abstract C1 [Pick, Chaim G. (Chagi); Rubovitch, Vardit; Rachmany, Lital] Tel Aviv Univ, Sackler Sch Med, Dept Anat & Anthropol, IL-69978 Tel Aviv, Israel. [Tweedie, David; Greig, Nigel H.] NIA, Neurosci Lab, Intramural Res Program, NIH, Baltimore, MD 21224 USA. [Hoffer, Barry J.] NIDA, Cellular Neurobiol Branch, Intramural Res Program, Baltimore, MD USA. [Schreiber, Shaul] Tel Aviv Univ, Tel Aviv Sourasky Med Ctr, Dept Psychiat, IL-69978 Tel Aviv, Israel. [Schreiber, Shaul] Tel Aviv Univ, Sackler Fac Med, IL-69978 Tel Aviv, Israel. RI Schreiber, Shaul/E-5821-2010 OI Schreiber, Shaul/0000-0002-2189-0693 NR 0 TC 0 Z9 0 U1 0 U2 4 PU INFORMA HEALTHCARE PI LONDON PA TELEPHONE HOUSE, 69-77 PAUL STREET, LONDON EC2A 4LQ, ENGLAND SN 0269-9052 J9 BRAIN INJURY JI Brain Inj. PD APR-MAY PY 2012 VL 26 IS 4-5 MA 0086 BP 340 EP 341 PG 2 WC Neurosciences; Rehabilitation SC Neurosciences & Neurology; Rehabilitation GA 943EZ UT WOS:000304104600064 ER PT J AU Zafonte, R Ansel, B Freidwald, W Novack, T Timmons, S Eisenberg, H Ricker, J Merchant, R Temkin, N Jallo, J Bagiella, E AF Zafonte, Ross Ansel, Beth Freidwald, William Novack, Thomas Timmons, Shelly Eisenberg, Howard Ricker, Joe Merchant, Randall Temkin, Nancy Jallo, Jack Bagiella, Emilia TI Results of the citicoline brain injury treatment (COBRIT) trial SO BRAIN INJURY LA English DT Meeting Abstract C1 NIH, Bethesda, MD 20892 USA. Columbia Univ, NYC, New York, NY USA. Univ Alabama Birmingham, Birmingham, AL USA. Univ Maryland, Baltimore, MD 21201 USA. Univ Pittsburgh, Pittsburgh, PA USA. Virginia Commonwealth Univ, Richmond, VA USA. Univ Washington, Seattle, WA 98195 USA. Thomas Jefferson Univ, Philadelphia, PA 19107 USA. NYC, Mt Sinai Sch Med, New York, NY USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU INFORMA HEALTHCARE PI LONDON PA TELEPHONE HOUSE, 69-77 PAUL STREET, LONDON EC2A 4LQ, ENGLAND SN 0269-9052 J9 BRAIN INJURY JI Brain Inj. PD APR-MAY PY 2012 VL 26 IS 4-5 MA 0182 BP 389 EP 389 PG 1 WC Neurosciences; Rehabilitation SC Neurosciences & Neurology; Rehabilitation GA 943EZ UT WOS:000304104600153 ER PT J AU Balasubbu, S Krishnadas, SR Jiao, XD Hejtmancik, JF Sundaresan, P AF Balasubbu, Suganthalakshmi Krishnadas, Subbaiah R. Jiao, Xiaodong Hejtmancik, J. Fielding Sundaresan, Periasamy TI Evaluation of SNPs on Chromosome 2p with Primary Open Angle Glaucoma in the South Indian Cohort SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Article ID GENOME-WIDE SCAN; BARBADOS; IDENTIFICATION; ASSOCIATION; POPULATION; VARIANTS; DISEASE; RISK; GENE; POAG AB PURPOSE. Glaucoma comprises a heterogeneous group of optic neuropathies with a complex genetic basis. It is the second leading cause of irreversible blindness in the world. This study investigates the association of SNPs on chromosome 2p with primary open angle glaucoma (POAG) in a Southern Indian population. METHODS. Case-control analysis was performed using 220 unrelated POAG cases and 220 age-matched unaffected controls recruited through the Aravind Eye Hospital and its outlying clinics. Five SNPs (rs1533428, rs12994401, rs10202118, rs11125375, and rs11889995) on chromosome 2p were evaluated in these two groups and genotyped using Taq Man SNP genotyping assay. Statistical analysis was performed using the SVS program package by Golden Helix to identify the distributions of allele and genotype frequencies, Fisher exact test P values, and odds ratios and to check Hardy-Weinberg equilibrium. RESULTS. Among the five SNPs screened, SNP rs10202118, showed a P = 0.026 for the basic allelic test, P = 0.004 for the genotypic test, and P = 0.0014 for the recessive model. The second suggestive marker was rs11125375, which also showed P = 0.033 for the recessive model. The associated SNPs formed a common disease haplotype. The remaining three SNPs showed insignificant association in this study population. CONCLUSIONS. This was the first study to demonstrate the association of SNPs on chromosome 2p in patients with POAG in the Indian population. The two tagging SNPs (rs10202118 and rs11125375) on chromosome 2p are the most likely sites underlying the significant association with POAG in this study population. (Invest Ophthalmol Vis Sci. 2012;53:1861-1864) DOI:10.1167/iovs.11-8602 C1 [Balasubbu, Suganthalakshmi; Sundaresan, Periasamy] Aravind Eye Hosp, Dr G Venkataswamy Eye Res Inst, Dept Genet, Aravind Med Res Fdn, Madurai 625020, Tamil Nadu, India. [Krishnadas, Subbaiah R.] Aravind Eye Hosp, Glaucoma Clin, Madurai 625020, Tamil Nadu, India. [Jiao, Xiaodong; Hejtmancik, J. Fielding] NEI, Ophthalm Genet & Visual Funct Branch, NIH, Rockville, MD USA. RP Sundaresan, P (reprint author), Aravind Eye Hosp, Dr G Venkataswamy Eye Res Inst, Dept Genet, Aravind Med Res Fdn, 1 Anna Nagar, Madurai 625020, Tamil Nadu, India. EM sundar@aravind.org FU Alcon; Aravind Medical Research Foundation FX Supported by Alcon, Aravind Medical Research Foundation. NR 22 TC 4 Z9 4 U1 0 U2 0 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI ROCKVILLE PA 12300 TWINBROOK PARKWAY, ROCKVILLE, MD 20852-1606 USA SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD APR PY 2012 VL 53 IS 4 BP 1861 EP 1864 DI 10.1167/iovs.11-8602 PG 4 WC Ophthalmology SC Ophthalmology GA 937PC UT WOS:000303669400021 PM 22410552 ER PT J AU Dauner, JG Pan, YJ Hildesheim, A Kemp, TJ Porras, C Pinto, LA AF Dauner, Joseph G. Pan, Yuanji Hildesheim, Allan Kemp, Troy J. Porras, Carolina Pinto, Ligia A. TI Development and application of a GuHCl-modified ELISA to measure the avidity of anti-HPV L1 VLP antibodies in vaccinated individuals SO MOLECULAR AND CELLULAR PROBES LA English DT Article DE HPV vaccine; Antibody; Avidity ID VIRUS-LIKE PARTICLES; HUMAN-PAPILLOMAVIRUS TYPE-16; IMMUNOGLOBULIN-G; STREPTOCOCCUS-PNEUMONIAE; MONOCLONAL-ANTIBODIES; COMBINATION VACCINES; THIOCYANATE ELUTION; CONJUGATE VACCINES; IMMUNE-RESPONSES; RHESUS MACAQUES AB Antibody responses against infectious agents are an important component in the prevention of disease. The avidity of antibodies for their antigens relates to their functional efficiency, and is a fundamental aspect in the investigation of humoral responses. Modified ELISAs are used to estimate avidity through the use of chaotropic agents and the measurement of the degree to which they disrupt the interaction between antibody and antigen. The theory behind the assay is the higher the avidity of an interaction the less susceptible it is to the effects of the chaotropic agent. The goal of this study was to generate a modified ELISA where a complex, multimeric coating-antigen, human papillomavirus (HPV) virus-like particles (VLP), was used to measure the avidity of anti-HPV antibodies generated following vaccination with HPV VLPs. A series of chaotropic agents were evaluated in the assay for their effectiveness in measuring avidity. Guanidine hydrochloride (GuHCl) was selected as a chaotropic reagent with the ability to disrupt antibody and antigen interactions, while not affecting the integrity of the plate-bound VLP. Two methods of determining the avidity index were assessed and shown to be comparable. This assay was then successfully applied to measure the avidity of anti-HPV VLP serum antibodies in samples from an HPV L1 VLP vaccine clinical trial. Overall, the assay was highly reproducible and captured a wide range of antibody avidities. Therefore, a GuHCl-modifiecl ELISA is an acceptable method that can be used to determine HPV-specific antibody avidity indices within a clinical trial setting. (C) 2012 Elsevier Ltd. All rights reserved. C1 [Dauner, Joseph G.; Pan, Yuanji; Kemp, Troy J.; Pinto, Ligia A.] NCI, HPV Immunol Lab, SAIC Frederick Inc, Frederick, MD 21702 USA. [Hildesheim, Allan] NCI, Div Canc Epidemiol & Genet, NIH, Bethesda, MD 20892 USA. RP Pinto, LA (reprint author), NCI, HPV Immunol Lab, SAIC Frederick Inc, Bldg 469,Room 120, Frederick, MD 21702 USA. EM pintol@mail.nih.gov RI Hildesheim, Allan/B-9760-2015 OI Hildesheim, Allan/0000-0003-0257-2363 FU NCI; NCI, the National Institutes of Health Office for Research on Women's Health (ORWH); GSK Bio [FDA BB-IND 7920]; National Cancer Institute, National Institutes of Health [HHSN261200800001E] FX The Costa Rica HPV Vaccine Trial is a long-standing collaboration between investigators in Costa Rica and the NCI. The trial is sponsored by the NCI, and conducted with support from the Ministry of Health of Costa Rica. This project has been funded in part by the NCI Intramural Research Program, the National Institutes of Health Office for Research on Women's Health (ORWH). Vaccine was provided for our trial by GlaxoSmithKline Biologicals (GSK Bio, Rixensart, Belgium), under a Clinical Trials Agreement with the NCI. GSK Bio also provided support for aspects of the trial associated with regulatory submission needs of the company under grant FDA BB-IND 7920. Laboratory testing was performed at the NCI-sponsored SAIC-Frederick, Inc. HPV Immunology Laboratory in Frederick, MD. The NCI and Costa Rica investigators are responsible for the design and conduct of the study; collection, management, analysis, and interpretation of the data; and preparation of the manuscript. The NCI and Costa Rica investigators make final editorial decisions on this and subsequent publications; GSK Bio has the right to review and comment.; This project has been funded in whole or in part with federal funds from the National Cancer Institute, National Institutes of Health, under Contract No. HHSN261200800001E. The content of this publication does not necessarily reflect the views or policies of the Department of Health and Human Services, nor does mention of trade names, commercial products, or organizations imply endorsement by the U.S. Government. NR 39 TC 10 Z9 10 U1 0 U2 7 PU ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD PI LONDON PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND SN 0890-8508 J9 MOL CELL PROBE JI Mol. Cell. Probes PD APR PY 2012 VL 26 IS 2 BP 73 EP 80 DI 10.1016/j.mcp.2012.01.002 PG 8 WC Biochemical Research Methods; Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Cell Biology SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Cell Biology GA 944UF UT WOS:000304228600003 PM 22285687 ER PT J AU Boja, ES Rodriguez, H AF Boja, Emily S. Rodriguez, Henry TI Mass spectrometry-based targeted quantitative proteomics: Achieving sensitive and reproducible detection of proteins SO PROTEOMICS LA English DT Review DE Biomarker verification; Multiple reaction monitoring mass spectrometry; Posttranslational modifications; Protein quantitation; Systems biology; Technology ID ACTIVITY-BASED PROBES; STABLE-ISOTOPE DILUTION; ABSOLUTE QUANTIFICATION; PEPTIDE ENRICHMENT; MULTIPLEXED ASSAYS; PLASMA PROTEOME; MAGNETIC BEADS; CANCER; BIOMARKER; SERUM AB Traditional shotgun proteomics used to detect a mixture of hundreds to thousands of proteins through mass spectrometric analysis, has been the standard approach in research to profile protein content in a biological sample which could lead to the discovery of new (and all) protein candidates with diagnostic, prognostic, and therapeutic values. In practice, this approach requires significant resources and time, and does not necessarily represent the goal of the researcher who would rather study a subset of such discovered proteins (including their variations or posttranslational modifications) under different biological conditions. In this context, targeted proteomics is playing an increasingly important role in the accurate measurement of protein targets in biological samples in the hope of elucidating the molecular mechanism of cellular function via the understanding of intricate protein networks and pathways. One such (targeted) approach, selected reaction monitoring (or multiple reaction monitoring) mass spectrometry (MRM-MS), offers the capability of measuring multiple proteins with higher sensitivity and throughput than shotgun proteomics. Developing and validating MRM-MS-based assays, however, is an extensive and iterative process, requiring a coordinated and collaborative effort by the scientific community through the sharing of publicly accessible data and datasets, bioinformatic tools, standard operating procedures, and well characterized reagents. C1 [Boja, Emily S.; Rodriguez, Henry] NCI, Off Canc Clin Prote Res, NIH, Bethesda, MD 20892 USA. RP Boja, ES (reprint author), NCI, Off Canc Clin Prote Res, NIH, 31 Ctr Dr,MS 2580, Bethesda, MD 20892 USA. EM bojae@mail.nih.gov NR 93 TC 76 Z9 77 U1 6 U2 79 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1615-9853 J9 PROTEOMICS JI Proteomics PD APR PY 2012 VL 12 IS 8 BP 1093 EP 1110 DI 10.1002/pmic.201100387 PG 18 WC Biochemical Research Methods; Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 940UI UT WOS:000303918200003 PM 22577011 ER PT J AU Barrett, J Bollard, CM AF Barrett, John Bollard, Catherine M. TI T-cell therapy for cancer SO IMMUNOTHERAPY LA English DT Editorial Material DE adoptive transfer; cytotoxic T cells; graft-versus-leukemia ID HODGKIN-LYMPHOMA; LYMPHOPROLIFERATIVE DISEASE; METASTATIC MELANOMA; ADOPTIVE TRANSFER; LYMPHOCYTES; EBV; TRANSPLANTATION; RESPONSES; LEUKEMIA; HUMANS C1 [Bollard, Catherine M.] Texas Childrens Hosp, Baylor Coll Med, Ctr Cell & Gene Therapy, Houston, TX 77030 USA. [Barrett, John] NHLBI, Hematol Branch, NIH, Bethesda, MD 20892 USA. RP Bollard, CM (reprint author), Texas Childrens Hosp, Baylor Coll Med, Ctr Cell & Gene Therapy, Houston, TX 77030 USA. EM cmbollar@txch.org NR 40 TC 2 Z9 2 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 1750-743X J9 IMMUNOTHERAPY-UK JI Immunotherapy PD APR PY 2012 VL 4 IS 4 BP 347 EP 350 DI 10.2217/IMT.12.12 PG 4 WC Immunology SC Immunology GA 937VP UT WOS:000303691400001 PM 22512624 ER PT J AU Nakashima, H Husain, SR Puri, RK AF Nakashima, Hideyuki Husain, Syed R. Puri, Raj K. TI IL-13 receptor-directed cancer vaccines and immunotherapy SO IMMUNOTHERAPY LA English DT Review DE combination therapy; DNA vaccine; IL-13 receptor alpha 2; immunotoxin; myeloid-derived suppressor cells ID MYELOID SUPPRESSOR-CELLS; REGULATORY T-CELLS; GLIOMA-ASSOCIATED ANTIGENS; MURINE TUMOR-MODELS; INTERLEUKIN-13 RECEPTOR; ALPHA-2 CHAIN; PSEUDOMONAS EXOTOXIN; SIGNAL-TRANSDUCTION; IMMUNE-RESPONSE; ANTICANCER THERAPY AB Many immunotherapy approaches including therapeutic cancer vaccines targeting specific tumor-associated antigens are at various stages of development. Although the significance of overexpression of (IL-13R alpha 2) in cancer is being actively investigated, we have reported that IL-13R alpha 2 is a novel tumor-associated antigen. The IL-13R alpha 2-directed cancer vaccine is one of the most promising approaches to tumor immunotherapy, because of the selective expression of IL-13R alpha 2 in various solid tumor types but not in normal tissues. In this article, we will summarize its present status and potential strategies to improve IL-13R alpha 2-directed cancer vaccines for an optimal therapy of cancer. C1 [Nakashima, Hideyuki; Husain, Syed R.; Puri, Raj K.] US FDA, Tumor Vaccines & Biotechnol Branch, Div Cellular & Gene Therapies, Ctr Biol Evaluat & Res, Bethesda, MD 20892 USA. RP Puri, RK (reprint author), US FDA, Tumor Vaccines & Biotechnol Branch, Div Cellular & Gene Therapies, Ctr Biol Evaluat & Res, NIH Bldg 29B,Room 2NN20,29 Lincoln Dr, Bethesda, MD 20892 USA. EM raj.puri@fda.hhs.gov NR 79 TC 10 Z9 10 U1 0 U2 2 PU FUTURE MEDICINE LTD PI LONDON PA UNITEC HOUSE, 3RD FLOOR, 2 ALBERT PLACE, FINCHLEY CENTRAL, LONDON, N3 1QB, ENGLAND SN 1750-743X J9 IMMUNOTHERAPY-UK JI Immunotherapy PD APR PY 2012 VL 4 IS 4 BP 443 EP 451 DI 10.2217/IMT.12.28 PG 9 WC Immunology SC Immunology GA 937VP UT WOS:000303691400017 PM 22512637 ER PT J AU Hamilton, JG Lobel, M AF Hamilton, Jada G. Lobel, Marci TI Passing years, changing fears? Conceptualizing and measuring risk perceptions for chronic disease in younger and middle-aged women SO JOURNAL OF BEHAVIORAL MEDICINE LA English DT Article DE Risk perception; Perceived vulnerability; Chronic disease; Women's health; Structural equation modeling ID BREAST-CANCER; PERCEIVED RISK; HEALTH BEHAVIOR; SUSCEPTIBILITY; VICTIMIZATION; VULNERABILITY; PERSONALITY; PSYCHOLOGY; KNOWLEDGE AB As is true for many behavioral theory constructs, no consensus exists on how best to measure perceived risk; therefore, it is unclear whether different measures of disease risk perception are conceptually equivalent and whether such measures are equally appropriate for people with different objective disease risk. To investigate these issues, we used four commonly utilized risk perception items (measuring beliefs about personal risk, others' risk, disease prevalence, and mortality) to assess susceptibility to cardiovascular disease, breast cancer, and lung cancer among 454 younger (ages 18-25) and 169 middle-aged (40-64) women. We examined age-and ethnicity-related differences in participants' responses to the items. We also used structural equation modeling to test whether these items reflect a multidimensional, disease-specific latent construct of risk perception; and to test whether consistency exists in participants' disease-specific risk perceptions. Despite differences in responses to individual items, hypothesized models of perceived risk fit both age groups, suggesting that risk perception can be conceptualized in younger and middle-aged women as a multidimensional construct that is specific to disease yet reflective of global risk-related beliefs. C1 [Hamilton, Jada G.; Lobel, Marci] SUNY Stony Brook, Dept Psychol, Stony Brook, NY 11794 USA. RP Hamilton, JG (reprint author), NCI, Canc Prevent Fellowship Program, Ctr Canc Training, Proc Care Res,Branch Behav Res Program,Div Canc C, 6130 Execut Blvd,Room 4051C,MSC 7331, Bethesda, MD 20892 USA. EM hamiltonjg@mail.nih.gov NR 49 TC 3 Z9 3 U1 1 U2 8 PU SPRINGER/PLENUM PUBLISHERS PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0160-7715 J9 J BEHAV MED JI J. Behav. Med. PD APR PY 2012 VL 35 IS 2 BP 124 EP 138 DI 10.1007/s10865-011-9342-8 PG 15 WC Psychology, Clinical SC Psychology GA 940BP UT WOS:000303865300002 PM 21487721 ER PT J AU Okano, J Lichti, U Mamiya, S Aronova, M Zhang, GF Yuspa, SH Hamada, H Sakai, Y Morasso, MI AF Okano, Junko Lichti, Ulrike Mamiya, Satoru Aronova, Maria Zhang, Guofeng Yuspa, Stuart H. Hamada, Hiroshi Sakai, Yasuo Morasso, Maria I. TI Increased retinoic acid levels through ablation of Cyp26b1 determine the processes of embryonic skin barrier formation and peridermal development SO JOURNAL OF CELL SCIENCE LA English DT Article DE Retinoic acid; Cyp26b1; Periderm; Skin differentiation; Skin barrier formation; Filaggrin ID CORNIFIED ENVELOPE; EPIDERMAL BARRIER; TERMINAL DIFFERENTIATION; ATOPIC-DERMATITIS; INTEGRATED VIEW; CLEFT-PALATE; EXPRESSION; MICE; GENE; FILAGGRIN AB The process by which the periderm transitions to stratified epidermis with the establishment of the skin barrier is unknown. Understanding the cellular and molecular processes involved is crucial for the treatment of human pathologies, where abnormal skin development and barrier dysfunction are associated with hypothermia and perinatal dehydration. For the first time, we demonstrate that retinoic acid (RA) levels are important for periderm desquamation, embryonic skin differentiation and barrier formation. Although excess exogenous RA has been known to have teratogenic effects, little is known about the consequences of elevated endogenous retinoids in skin during embryogenesis. Absence of cytochrome P450, family 26, subfamily b, polypeptide 1 (Cyp26b1), a retinoic-acid-degrading enzyme, results in aberrant epidermal differentiation and filaggrin expression, defective cornified envelopes and skin barrier formation, in conjunction with peridermal retention. We show that these alterations are RA dependent because administration of exogenous RA in vivo and to organotypic skin cultures phenocopy Cyp26b1(-/-) skin abnormalities. Furthermore, utilizing the Flaky tail (Ft/Ft) mice, a mouse model for human ichthyosis, characterized by mutations in the filaggrin gene, we establish that proper differentiation and barrier formation is a prerequisite for periderm sloughing. These results are important in understanding pathologies associated with abnormal embryonic skin development and barrier dysfunction. C1 [Okano, Junko; Morasso, Maria I.] NIAMS, Dev Skin Biol Sect, NIH, Bethesda, MD 20892 USA. [Lichti, Ulrike; Yuspa, Stuart H.] NCI, Lab Canc Biol & Genet, NIH, Bethesda, MD 20892 USA. [Mamiya, Satoru; Hamada, Hiroshi] Osaka Univ, Grad Sch Frontier Biosci, Dev Genet Grp, Suita, Osaka 5650871, Japan. [Aronova, Maria; Zhang, Guofeng] NIBIB, Lab Bioengn & Phys Sci, NIH, Bethesda, MD 20892 USA. [Sakai, Yasuo] Osaka Univ, Sch Med, Dept Plast Surg, Suita, Osaka 5650871, Japan. RP Morasso, MI (reprint author), NIAMS, Dev Skin Biol Sect, NIH, Bethesda, MD 20892 USA. EM morasso@nih.gov FU National Institute of Arthritis and Musculoskeletal and Skin Diseases, National Institutes of Health FX This study was supported by an Intramural Research Program of the National Institute of Arthritis and Musculoskeletal and Skin Diseases, National Institutes of Health. Deposited in PMC for release after 12 months. NR 56 TC 11 Z9 11 U1 1 U2 6 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 APR 1 PY 2012 VL 125 IS 7 BP 1827 EP 1836 DI 10.1242/jcs.101550 PG 10 WC Cell Biology SC Cell Biology GA 940RR UT WOS:000303911300022 PM 22366455 ER PT J AU Riley, BD Culver, JO Skrzynia, C Senter, LA Peters, JA Costalas, JW Callif-Daley, F Grumet, SC Hunt, KS Nagy, RS McKinnon, WC Petrucelli, NM Bennett, RL Trepanier, AM AF Riley, Bronson D. Culver, Julie O. Skrzynia, Cecile Senter, Leigha A. Peters, June A. Costalas, Josephine W. Callif-Daley, Faith Grumet, Sherry C. Hunt, Katherine S. Nagy, Rebecca S. McKinnon, Wendy C. Petrucelli, Nancie M. Bennett, Robin L. Trepanier, Angela M. TI Essential Elements of Genetic Cancer Risk Assessment, Counseling, and Testing: Updated Recommendations of the National Society of Genetic Counselors SO JOURNAL OF GENETIC COUNSELING LA English DT Article DE Cancer genetic counseling; Risk assessment; Genetic testing; Family history; Psychosocial assessment; Hereditary cancer; Informed consent ID BRCA2 MUTATION CARRIERS; POLICY STATEMENT UPDATE; BREAST-CANCER; LYNCH-SYNDROME; OVARIAN-CANCER; HEREDITARY CANCER; FAMILY-HISTORY; PREDISPOSITION SYNDROMES; PSYCHOLOGICAL IMPACT; AMERICAN-SOCIETY AB Updated from their original publication in 2004, these cancer genetic counseling recommendations describe the medical, psychosocial, and ethical ramifications of counseling at-risk individuals through genetic cancer risk assessment with or without genetic testing. They were developed by members of the Practice Issues Subcommittee of the National Society of Genetic Counselors Familial Cancer Risk Counseling Special Interest Group. The information contained in this document is derived from extensive review of the current literature on cancer genetic risk assessment and counseling as well as the personal expertise of genetic counselors specializing in cancer genetics. The recommendations are intended to provide information about the process of genetic counseling and risk assessment for hereditary cancer disorders rather than specific information about individual syndromes. Essential components include the intake, cancer risk assessment, genetic testing for an inherited cancer syndrome, informed consent, disclosure of genetic test results, and psychosocial assessment. These recommendations should not be construed as dictating an exclusive course of management, nor does use of such recommendations guarantee a particular outcome. These recommendations do not displace a health care provider's professional judgment based on the clinical circumstances of a client. C1 [Riley, Bronson D.] SE Nebraska Canc Ctr, Lincoln, NE USA. [Culver, Julie O.] City Hope Natl Med Ctr, Div Clin Canc Genet, Duarte, CA USA. [Skrzynia, Cecile] Univ N Carolina, Dept Med, Chapel Hill, NC USA. [Skrzynia, Cecile] Univ N Carolina, Dept Genet, Chapel Hill, NC USA. [Senter, Leigha A.] Ohio State Univ, Div Human Genet, Columbus, OH 43210 USA. [Peters, June A.] NCI, Clin Genet Branch, Div Canc Epidemiol & Genet, Rockville, MD USA. [Costalas, Josephine W.] St Mary Reg Canc Ctr, Langhorne, PA USA. [Callif-Daley, Faith] Childrens Med Ctr Dayton, Dept Med Genet, Dayton, OH USA. [Grumet, Sherry C.] Monmouth Med Ctr, Leon Hess Canc Ctr, Long Branch, NJ USA. [Hunt, Katherine S.] Mayo Coll Med, Scottsdale, AZ USA. [Nagy, Rebecca S.] Ohio State Univ, Clin Canc Genet Program, James Canc Hosp, Columbus, OH 43210 USA. [Nagy, Rebecca S.] Ohio State Univ, Solove Res Inst, Columbus, OH 43210 USA. [McKinnon, Wendy C.] Fletcher Allen Hlth Care, Vermont Reg Genet Ctr, Dept Pediat, Burlington, VT USA. [Petrucelli, Nancie M.] Karmanos Canc Inst, Detroit, MI USA. [Bennett, Robin L.] Univ Washington, Div Med Genet, Med Ctr, Seattle, WA 98195 USA. [Trepanier, Angela M.] Wayne State Univ, Sch Med, Ctr Mol Med & Genet, Detroit, MI USA. RP Riley, BD (reprint author), SE Nebraska Canc Ctr, Lincoln, NE USA. EM bronsonr@leadingcancercare.com RI Shrigley Nagy, Rebecca/E-4088-2011 NR 79 TC 83 Z9 87 U1 4 U2 15 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1059-7700 J9 J GENET COUNS JI J. Genet. Couns. PD APR PY 2012 VL 21 IS 2 BP 151 EP 161 DI 10.1007/s10897-011-9462-x PG 11 WC Genetics & Heredity SC Genetics & Heredity GA 940LC UT WOS:000303890000001 PM 22134580 ER PT J AU Yoshinaga, K AF Yoshinaga, Koji TI Two Concepts on the Immunological Aspect of Blastocyst Implantation SO JOURNAL OF REPRODUCTION AND DEVELOPMENT LA English DT Review DE Blastocyst implantation; Concepts; Immune aspect ID LEUKEMIA INHIBITORY FACTOR; HUMAN CHORIONIC-GONADOTROPIN; COLONY-STIMULATING FACTOR; FACTOR GENE-EXPRESSION; ENDOMETRIAL EPITHELIAL-CELLS; PREIMPLANTATION MOUSE EMBRYO; DECAY-ACCELERATING FACTOR; UTERINE RECEPTIVITY; CANNABINOID RECEPTOR; DENDRITIC CELLS AB The process of blastocyst implantation is a series of interactions between the blastocyst and maternal tissues. The purpose of this process is (1) to provide nourishment to the embryo for developmental growth in appropriate physiological and endocrinological environment until a placenta is established, and (2) to protect the (semi-)allogeneic embryo from any attacks from the maternal immune system. To facilitate successful implantation, therefore, these two aspects of the embryonic demand must be satisfied in the embryo-maternal interface throughout the entire process of implantation. The first concept I present in this paper is that blastocyst implantation essential factors (BIEFs) have dual functions: one, for structural and functional modification of the endometrium to accommodate the developing embryo and provide nourishment and suitable environment for its development, and the other, for modulation, directly or indirectly, of the maternal immune system to prevent attacks by the maternal immune system. The second concept is that BIEFs convert the endometrium (or uterus) from an immunologically non-privileged site to a privileged site. This endometrial (uterine) conversion is the immunological aspect of the blastocyst implantation process. When the endometrium has become receptive for blastocyst implantation, it signifies that the immunological conversion of the endometrium by BIEFs has been sufficiently attained to let the embryo start contacting maternal tissues. During the early stages of placentation, as the trophoblast cells differentiate and make their way to the maternal blood vessels to establish the placenta, BIEFs continuously provide nourishment and immunological protection to the developing embryo. The immunological protection or the embryo/fetus from potential attacks by the maternal immune system appears to reach a peak at the time of establishment of the placenta. Thus, clarification of the roles of BIEFs in both the physiological/endocrinological aspect as well as the immunological aspect is essential for understanding the biological process of implantation. C1 NICHD, Reprod Sci Branch, NIH, DHHS, Bethesda, MD 20892 USA. RP Yoshinaga, K (reprint author), NICHD, Reprod Sci Branch, NIH, DHHS, Bethesda, MD 20892 USA. EM ky6a@nih.gov NR 99 TC 9 Z9 10 U1 1 U2 7 PU SOCIETY REPRODUCTION & DEVELOPMENT-SRD PI TSUKUBA PA C/O KAZUHIRO KIKUCHI, PHD DVM, NATL INST AGROBIOLOGICAL SCIENCES KANNONDAI 2-1-2, TSUKUBA, IBARAKI 305-8602, JAPAN SN 0916-8818 J9 J REPROD DEVELOP JI J. Reprod. Dev. PD APR PY 2012 VL 58 IS 2 BP 196 EP 203 PG 8 WC Agriculture, Dairy & Animal Science; Reproductive Biology SC Agriculture; Reproductive Biology GA 939BV UT WOS:000303782800005 PM 22738903 ER PT J AU Aschebrook-Kilfoy, B Ward, MH Zheng, TZ Holford, TR Boyle, P Leaderer, B Zhang, YW AF Aschebrook-Kilfoy, Briseis Ward, Mary H. Zheng, Tongzhang Holford, Theodore R. Boyle, Peter Leaderer, Brian Zhang, Yawei TI Dietary Nitrate and Nitrite Intake and Non-Hodgkin Lymphoma Survival SO NUTRITION AND CANCER-AN INTERNATIONAL JOURNAL LA English DT Article ID N-NITROSO COMPOUNDS; UNITED-STATES; CANCER; CLASSIFICATION; SUBTYPE AB Nitrate and nitrite are precursors in the formation of N-nitroso compounds. We recently found a 40% increased risk of NHL with higher dietary nitrite intake and significant increases in risk for follicular and T-cell lymphoma. It is possible that these compounds also affect NHL prognosis by enhancing cancer progression in addition to development by further impairing immune system function. To test the hypothesis that nitrate and nitrite intake affects NHL survival, we evaluated the association in study participants that have been followed post-disease diagnosis in a population-based case-control study among women in Connecticut. We did not observe a significant increasing trend of mortality for NHL overall or by subtype for nitrate or nitrite intake for deaths from NHL or death from any cause, although a borderline significant protective trend was observed for follicular lymphoma with increasing nitrate intake. We did not identify a difference in overall survival for nitrate (P = 0.39) or for nitrite (P = 0.66) or for NHL specific survival for nitrate (P = 0.96) or nitrite (P = 0.17). Thus, our null findings do not confer support for the possibility that dietary nitrate and nitrite intake impacts NHL survival by promoting immune unresponsiveness. C1 [Aschebrook-Kilfoy, Briseis] Univ Chicago, Dept Hlth Studies, Chicago, IL 60637 USA. [Ward, Mary H.] NCI, Occupat & Environm Epidemiol Branch, Div Canc Epidemiol & Genet, NIH,Dept Hlth & Human Serv, Rockville, MD USA. [Zheng, Tongzhang; Holford, Theodore R.; Leaderer, Brian; Zhang, Yawei] Yale Univ, Yale Sch Publ Hlth, New Haven, CT USA. [Boyle, Peter] Int Prevent Res Inst, Lyon, France. RP Aschebrook-Kilfoy, B (reprint author), Univ Chicago, Dept Hlth Studies, 5841 S Maryland Ave,N101B, Chicago, IL 60637 USA. EM brisa@uchicago.edu RI Boyle, Peter/A-4380-2014 OI Boyle, Peter/0000-0001-6251-0610 FU Yale Cancer Center [22067A]; National Cancer Institute (NCI) [CA62006]; NCI, National Institutes of Health (NIH); NIH [1D43TW008323-01, 1D43TW007864-01]; CTSA from the National Center for Research Resources (NCRR), NIH [UL1 RR024139]; NHL roadmap for medical research FX This research was supported by Hull Argall and Anna Grant 22067A from the Yale Cancer Center, Grant CA62006 from the National Cancer Institute (NCI), the Intramural Research Program of the NCI, National Institutes of Health (NIH), and Fogarty Training Grant 1D43TW008323-01 and 1D43TW007864-01 from the NIH. This publication was made possible by CTSA Grant UL1 RR024139 from the National Center for Research Resources (NCRR), a component of the NIH, and NHL roadmap for medical research. Its contents are solely the responsibility of the authors and do not necessarily represent the official view of NCRR. This research was approved by the DPH HIC. Certain data used in this study were obtained from the Connecticut Department of Public Health. The authors assume full responsibility for analyses and interpretation of these data. NR 17 TC 3 Z9 3 U1 0 U2 1 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 PD APR PY 2012 VL 64 IS 3 BP 488 EP 492 DI 10.1080/01635581.2012.658136 PG 5 WC Oncology; Nutrition & Dietetics SC Oncology; Nutrition & Dietetics GA 937ZL UT WOS:000303702600015 PM 22420290 ER PT J AU Kelly, RJ Robey, RW Chen, CC Draper, D Luchenko, V Barnett, D Oldham, RK Caluag, Z Frye, AR Steinberg, SM Fojo, T Bates, SE AF Kelly, Ronan J. Robey, Robert W. Chen, Clara C. Draper, Deborah Luchenko, Victoria Barnett, Daryl Oldham, Robert K. Caluag, Zinnah Frye, A. Robin Steinberg, Seth M. Fojo, Tito Bates, Susan E. TI A Pharmacodynamic Study of the P-glycoprotein Antagonist CBT-1 (R) in Combination With Paclitaxel in Solid Tumors SO ONCOLOGIST LA English DT Article AB Background: This pharmacodynamic trial evaluated the effect of CBT-1 (R) on efflux by the ATP binding cassette (ABC) multidrug transporter P-glycoprotein (Pgp/MDR1/ABCB1) in normal human cells and tissues. CBT-1 (R) is an orally administered bisbenzylisoquinoline Pgp inhibitor being evaluated clinically. Laboratory studies showed potent and durable inhibition of Pgp, and in phase I studies CBT-1 (R) did not alter the pharmacokinetics of paclitaxel or doxorubicin. Methods: CBT-1 (R) was dosed at 500 mg/m(2) for 7 days; a 3-hour infusion of paclitaxel at 135 mg/m2 was administered on day 6. Peripheral blood mononuclear cells (PBMCs) were obtained prior to CBT-1 (R) administration and on day 6 prior to the paclitaxel infusion. Tc-99m-sestamibi imaging was performed on the same schedule. The area under the concentration-time curve from 0-3 hours (AUC(0-3)) was determined for Tc-99m-sestamibi. Results: Twelve patients were planned and enrolled. Toxicities were minimal and related to paclitaxel (grade 3 or 4 neutropenia in 18% of cycles). Rhodamine efflux from CD56(+) PBMCs was a statistically significant 51%-100% lower (p < .0001) with CBT-1 (R). Among 10 patients who completed imaging, the Tc-99m-sestamibi AUC(0-3) for liver (normalized to the AUC(0-3) of the heart) increased from 34.7% to 100.8% (median, 71.9%; p < .0001) after CBT-1 (R) administration. Lung uptake was not changed. Conclusion: CBT-1 (R) is able to inhibit Pgp-mediated efflux from PBMCs and normal liver to a degree observed with Pgp inhibitors studied in earlier clinical trials. Combined with its ease of administration and lack of toxicity, the data showing inhibition of normal tissue Pgp support further studies with CBT-1 (R) to evaluate its ability to modulate drug uptake in tumor tissue. Discussion: Although overexpression of ABCB1 and other ABC transporters has been linked with poor outcome following chemotherapy efforts to negate that through pharmacologic inhibition have generally failed. This is thought to be a result of several factors, including (a) failure to select patients with tumors in which ABCB1 is a dominant resistance mechanism; (b) inhibitors that were not potent, or that impaired drug clearance; and (c) the existence of other mechanisms of drug resistance, including other ABC transporters. Although an animal model for Pgp has been lacking, recent studies have exploited a Brca1(-/-); p53(-/-) mouse model of hereditary breast cancer that develops sporadic tumors similar to cancers in women harboring BRCA1 mutations. Treatment with doxorubicin, docetaxel, or the poly(ADP-ribose) polymerase inhibitor olaparib brings about shrinkage, but resistance eventually emerges. Overexpression of the Abcb1a gene, the mouse ortholog of human ABCB1, has been shown to be a mechanism of resistance in a subset of these tumors. Treating mice with resistant tumors with olaparib plus the Pgp inhibitor tariquidar resensitized the tumors to olaparib. Although results in this animal model support a new look at Pgp as a target, in this era of "targeted therapies," trial designs that directly assess modulation of drug uptake, including quantitative nuclear imaging, should be pursued before clinical efficacy assessments are undertaken. Such assessment should be performed with compounds that inhibit tissue Pgp without altering the pharmacokinetics of chemotherapeutic agents. This pharmacodynamic study demonstrated that CBT-1 (R),inhibits Pgp-mediated efflux from PBMCs and normal liver. C1 [Kelly, Ronan J.; Robey, Robert W.; Draper, Deborah; Luchenko, Victoria; Frye, A. Robin; Fojo, Tito; Bates, Susan E.] NIH, Med Oncol Branch, Ctr Canc Res, Bethesda, MD 20892 USA. [Steinberg, Seth M.] NIH, Biostat & Data Management Sect, Ctr Canc Res, Bethesda, MD 20892 USA. [Chen, Clara C.] NIH, Dept Nucl Med, Warren G Magnuson Clin Ctr, Bethesda, MD 20892 USA. [Chen, Clara C.] NIH, Dept Radiol, Warren G Magnuson Clin Ctr, Bethesda, MD 20892 USA. [Barnett, Daryl; Oldham, Robert K.; Caluag, Zinnah] CBA Res, Lexington, KY USA. RP Bates, SE (reprint author), 9000 Rockville Pike,Bldg 10,Room 12N226, Bethesda, MD 20892 USA. EM sebates@helix.nih.gov NR 0 TC 19 Z9 20 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 PD APR PY 2012 VL 17 IS 4 BP 512 EP 512 DI 10.1634/theoncologist.2012-0080 PG 1 WC Oncology SC Oncology GA 940FA UT WOS:000303874200009 PM 22416063 ER PT J AU Giorgobiani, E Lawyer, PG Babuadze, G Dolidze, N Jochim, RC Tskhvaradze, L Kikaleishvili, K Kamhawi, S AF Giorgobiani, Ekaterina Lawyer, Phillip G. Babuadze, Giorgi Dolidze, Nato Jochim, Ryan C. Tskhvaradze, Lamzira Kikaleishvili, Konstantin Kamhawi, Shaden TI Incrimination of Phlebotomus kandelakii and Phlebotomus balcanicus as Vectors of Leishmania infantum in Tbilisi, Georgia SO PLOS NEGLECTED TROPICAL DISEASES LA English DT Article ID VISCERAL LEISHMANIASIS; SEQUENCE ALIGNMENT; TRANSMISSION; PSYCHODIDAE; DIPTERA; FOCUS AB A survey of potential vector sand flies was conducted in the neighboring suburban communities of Vake and Mtatsminda districts in an active focus of visceral Leishmaniasis (VL) in Tbilisi, Georgia. Using light and sticky-paper traps, 1,266 male and 1,179 female sand flies were collected during 2006-2008. Five Phlebotomus species of three subgenera were collected: Phlebotomus balcanicus Theodor and Phlebotomus halepensis Theodor of the subgenus Adlerius; Phlebotomus kandelakii Shchurenkova and Phlebotomus wenyoni Adler and Theodor of the subgenus Larroussius; Phlebotomus sergenti Perfil'ev of the subgenus Paraphlebotomus. Phlebotomus sergenti (35.1%) predominated in Vake, followed by P. kandelakii (33.5%), P. balcanicus (18.9%), P. halepensis (12.2%), and P. wenyoni (0.3%). In Mtatsminda, P. kandelakii (76.8%) comprised over three fourths of collected sand flies, followed by P. sergenti (12.6%), P. balcanicus (5.8%), P. halepensis (3.7%), and P. wenyoni (1.1%). The sand fly season in Georgia is exceptionally short beginning in early June, peaking in July and August, then declining to zero in early September. Of 659 female sand flies examined for Leishmania, 12 (1.8%) specimens without traces of blood were infected including 10 of 535 P. kandelakii (1.9%) and two of 40 P. balcanicus (5.0%). Six isolates were successfully cultured and characterized as Leishmania by PCR. Three isolates from P. kandelakii (2) and P. balcanicus (1) were further identified as L. infantum using sequence alignment of the 70 kDa heat-shock protein gene. Importantly, the sand fly isolates showed a high percent identity (99.8%-99.9%) to human and dog isolates from the same focus, incriminating the two sand fly species as vectors. Blood meal analysis showed that P. kandelakii preferentially feeds on dogs (76%) but also feeds on humans. The abundance, infection rate and feeding behavior of P. kandelakii and the infection rate in P. balcanicus establish these species as vectors in the Tbilisi VL focus. C1 [Giorgobiani, Ekaterina; Babuadze, Giorgi; Dolidze, Nato; Tskhvaradze, Lamzira; Kikaleishvili, Konstantin] Natl Ctr Dis Control & Publ Hlth, Tbilisi, Rep of Georgia. [Lawyer, Phillip G.] NIAID, Parasit Dis Lab, NIH, Bethesda, MD 20892 USA. [Jochim, Ryan C.; Kamhawi, Shaden] NIAID, Lab Malaria & Vector Res, NIH, Rockville, MD USA. RP Giorgobiani, E (reprint author), Natl Ctr Dis Control & Publ Hlth, Tbilisi, Rep of Georgia. EM egiorgobiani@yahoo.com; skamhawi@niaid.nih.gov RI Jochim, Ryan/C-6756-2013 FU United States Department of Health and Human Services through the International Science and Technology Center [ISTC G-1081/BTEP N89]; Division of Intramural Research, National Institute of Allergy and Infectious Diseases FX This study was supported by the United States Department of Health and Human Services Biotechnology Engagement Program through the International Science and Technology Center (grant ISTC G-1081/BTEP N89) and by the Division of Intramural Research, National Institute of Allergy and Infectious Diseases. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 29 TC 12 Z9 12 U1 0 U2 5 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA SN 1935-2735 J9 PLOS NEGLECT TROP D JI Plos Neglect. Trop. Dis. PD APR PY 2012 VL 6 IS 4 AR e1609 DI 10.1371/journal.pntd.0001609 PG 10 WC Infectious Diseases; Parasitology; Tropical Medicine SC Infectious Diseases; Parasitology; Tropical Medicine GA 935CP UT WOS:000303496800025 PM 22509422 ER PT J AU Gomes, R Teixeira, C Oliveira, F Lawyer, PG Elnaiem, DE Meneses, C Goto, Y Bhatia, A Howard, RF Reed, SG Valenzuela, JG Kamhawi, S AF Gomes, Regis Teixeira, Clarissa Oliveira, Fabiano Lawyer, Phillip G. Elnaiem, Dia-Eldin Meneses, Claudio Goto, Yasuyuki Bhatia, Ajay Howard, Randall F. Reed, Steven G. Valenzuela, Jesus G. Kamhawi, Shaden TI KSAC, a Defined Leishmania Antigen, plus Adjuvant Protects against the Virulence of L. major Transmitted by Its Natural Vector Phlebotomus duboscqi SO PLOS NEGLECTED TROPICAL DISEASES LA English DT Article ID CANINE VISCERAL LEISHMANIASIS; CUTANEOUS LEISHMANIASIS; LEISH-F1+MPL-SE VACCINE; POLYPROTEIN VACCINE; CLINICAL-TRIAL; SAND FLIES; T-CELLS; MEGLUMINE ANTIMONIATE; IMMUNOGENICITY; EVALUATE AB Background: Recombinant KSAC and L110f are promising Leishmania vaccine candidates. Both antigens formulated in stable emulsions (SE) with the natural TLR4 agonist MPL (R) and L110f with the synthetic TLR4 agonist GLA in SE protected BALB/c mice against L. major infection following needle challenge. Considering the virulence of vector-transmitted Leishmania infections, we vaccinated BALB/c mice with either KSAC+GLA-SE or L110f+GLA-SE to assess protection against L. major transmitted via its vector Phlebotomus duboscqi. Methods: Mice receiving the KSAC or L110f vaccines were challenged by needle or L. major-infected sand flies. Weekly disease progression and terminal parasite loads were determined. Immunological responses to KSAC, L110f, or soluble Leishmania antigen (SLA) were assessed throughout vaccination, three and twelve weeks after immunization, and one week post-challenge. Results: Following sand fly challenge, KSAC-vaccinated mice were protected while L110f-vaccinated animals showed partial protection. Protection correlated with the ability of SLA to induce IFN-gamma-producing CD4(+)CD62L(low)CCR7(low) effector memory T cells pre- and post-sand fly challenge. Conclusions: This study demonstrates the protective efficacy of KSAC+GLA-SE against sand fly challenge; the importance of vector-transmitted challenge in evaluating vaccine candidates against Leishmania infection; and the necessity of a rapid potent Th1 response against Leishmania to attain true protection. C1 [Gomes, Regis; Teixeira, Clarissa; Oliveira, Fabiano; Meneses, Claudio; Valenzuela, Jesus G.; Kamhawi, Shaden] NIAID, Vector Mol Biol Sect, Lab Malaria & Vector Res, NIH, Rockville, MD USA. [Lawyer, Phillip G.] NIAID, Parasit Dis Lab, NIH, Rockville, MD USA. [Elnaiem, Dia-Eldin] Eastern Shore Univ, Dept Zool, Eastern Shore Maryland, MD USA. [Goto, Yasuyuki; Bhatia, Ajay; Howard, Randall F.; Reed, Steven G.] Infect Dis Res Inst, Seattle, WA USA. RP Gomes, R (reprint author), NIAID, Vector Mol Biol Sect, Lab Malaria & Vector Res, NIH, Rockville, MD USA. EM jvalenzuela@niaid.nih.gov; skamhawi@niaid.nih.gov RI Goto, Yasuyuki/E-9028-2011; Oliveira, Fabiano/B-4251-2009 OI Goto, Yasuyuki/0000-0002-8654-7888; Oliveira, Fabiano/0000-0002-7924-8038 FU Division of Intramural Research, National Institute of Allergy and Infectious Diseases (NIAID); NIAID [AI-25038] FX The study was funded by the Division of Intramural Research, National Institute of Allergy and Infectious Diseases (NIAID) and supported in part by a grant from NIAID to SGR (AI-25038). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 34 TC 14 Z9 14 U1 0 U2 3 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA SN 1935-2735 J9 PLOS NEGLECT TROP D JI Plos Neglect. Trop. Dis. PD APR PY 2012 VL 6 IS 4 AR e1610 DI 10.1371/journal.pntd.0001610 PG 9 WC Infectious Diseases; Parasitology; Tropical Medicine SC Infectious Diseases; Parasitology; Tropical Medicine GA 935CP UT WOS:000303496800026 PM 22509423 ER PT J AU Sehba, FA Hou, J Pluta, RM Zhang, JH AF Sehba, Fatima A. Hou, Jack Pluta, Ryszard M. Zhang, John H. TI The importance of early brain injury after subarachnoid hemorrhage SO PROGRESS IN NEUROBIOLOGY LA English DT Review DE Subarachnoid hemorrhage; Vasospasm; Early brain injury; Animal models; Therapy failure ID CEREBRAL-BLOOD-FLOW; NITRIC-OXIDE SYNTHASE; INTERCELLULAR-ADHESION MOLECULE-1; ISCHEMIC NEUROLOGICAL DEFICITS; BARRIER PERMEABILITY CHANGES; SUB-ARACHNOID HEMORRHAGE; NEURON-SPECIFIC ENOLASE; CANINE BASILAR ARTERY; C-REACTIVE PROTEIN; ENDOTHELIUM-DEPENDENT RELAXATION AB Aneurysmal subarachnoid hemorrhage (aSAH) is a medical emergency that accounts for 5% of all stroke cases. Individuals affected are typically in the prime of their lives (mean age 50 years). Approximately 12% of patients die before receiving medical attention, 33% within 48 h and 50% within 30 days of aSAH. Of the survivors 50% suffer from permanent disability with an estimated lifetime cost more than double that of an ischemic stroke. Traditionally, spasm that develops in large cerebral arteries 3-7 days after aneurysm rupture is considered the most important determinant of brain injury and outcome after aSAH. However, recent studies show that prevention of delayed vasospasm does not improve outcome in aSAH patients. This finding has finally brought in focus the influence of early brain injury on outcome of aSAH. A substantial amount of evidence indicates that brain injury begins at the aneurysm rupture, evolves with time and plays an important role in patients' outcome. In this manuscript we review early brain injury after aSAH. Due to the early nature, most of the information on this injury comes from animals and few only from autopsy of patients who died within days after aSAH. Consequently, we began with a review of animal models of early brain injury, next we review the mechanisms of brain injury according to the sequence of their temporal appearance and finally we discuss the failure of clinical translation of therapies successful in animal models of aSAH. (C) 2012 Elsevier Ltd. All rights reserved. C1 [Sehba, Fatima A.] Mt Sinai Sch Med, Dept Neurosurg, New York, NY 10029 USA. [Sehba, Fatima A.] Mt Sinai Sch Med, Dept Neurosci, New York, NY 10029 USA. [Pluta, Ryszard M.] NINDS, Surg Neurol Branch, NIH, Bethesda, MD 20892 USA. [Hou, Jack; Zhang, John H.] Loma Linda Univ, Med Ctr, Dept Neurosurg, Loma Linda, CA USA. RP Sehba, FA (reprint author), Mt Sinai Sch Med, Dept Neurosurg, New York, NY 10029 USA. EM fatima.sehba@mssm.edu OI Zhang, John H./0000-0002-4319-4285 FU American Heart Organization [10GRNT4570012]; National Institutes of Health National Center for Research Resources [RO1 NS050576, NS053407]; National Institute of Neurological Disorders and Stroke FX This work was supported by American Heart Organization Grant [10GRNT4570012 (FAS)] and the National Institutes of Health National Center for Research Resources [RO1 NS050576 (FAS); NS053407 (JHZ)]; and by the Intramural Research Program (RMP) of the National Institute of Neurological Disorders and Stroke. NR 519 TC 130 Z9 144 U1 4 U2 34 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0301-0082 J9 PROG NEUROBIOL JI Prog. Neurobiol. PD APR PY 2012 VL 97 IS 1 BP 14 EP 37 DI 10.1016/j.pneurobio.2012.02.003 PG 24 WC Neurosciences SC Neurosciences & Neurology GA 939UY UT WOS:000303845600002 PM 22414893 ER PT J AU Akhter, I Simon, T Khan, S Matthews, I Sheikh, Y AF Akhter, Ijaz Simon, Tomas Khan, Sohaib Matthews, Iain Sheikh, Yaser TI Bilinear Spatiotemporal Basis Models SO ACM TRANSACTIONS ON GRAPHICS LA English DT Article DE Algorithms; Theory; Measurement; Bilinear models; spatiotemporal; motion data; motion capture ID ACTIVE SHAPE MODELS; HUMAN MOTION; CARDIAC MR; ANIMATION; CAPTURE; TRACKING; SPACES; STYLE AB A variety of dynamic objects, such as faces, bodies, and cloth, are represented in computer graphics as a collection of moving spatial landmarks. Spatiotemporal data is inherent in a number of graphics applications including animation, simulation, and object and camera tracking. The principal modes of variation in the spatial geometry of objects are typically modeled using dimensionality reduction techniques, while concurrently, trajectory representations like splines and autoregressive models are widely used to exploit the temporal regularity of deformation. In this article, we present the bilinear spatiotemporal basis as a model that simultaneously exploits spatial and temporal regularity while maintaining the ability to generalize well to new sequences. This factorization allows the use of analytical, predefined functions to represent temporal variation (e.g., B-Splines or the Discrete Cosine Transform) resulting in efficient model representation and estimation. The model can be interpreted as representing the data as a linear combination of spatiotemporal sequences consisting of shape modes oscillating over time at key frequencies. We apply the bilinear model to natural spatiotemporal phenomena, including face, body, and cloth motion data, and compare it in terms of compaction, generalization ability, predictive precision, and efficiency to existing models. We demonstrate the application of the model to a number of graphics tasks including labeling, gap-filling, denoising, and motion touch-up. C1 [Akhter, Ijaz] Disney Res Pittsburgh, LUMS Sch Sci & Engn, Pittsburgh, PA USA. [Simon, Tomas; Matthews, Iain] Carnegie Mellon Univ, Disney Res Pittsburgh, Pittsburgh, PA 15213 USA. [Khan, Sohaib] Lahore Univ Management Sci, LUMS Sch Sci & Engn, Lahore, Pakistan. [Sheikh, Yaser] Carnegie Mellon Univ, Dept Comp Sci, Pittsburgh, PA 15213 USA. RP Akhter, I (reprint author), Disney Res Pittsburgh, LUMS Sch Sci & Engn, Pittsburgh, PA USA. EM akhter@lums.edu.pk; tsimon@cmu.edu; sohaib@lums.edu.pk; iainm@disneyresearch.com; yaser@cs.cmu.edu NR 58 TC 7 Z9 7 U1 1 U2 5 PU ASSOC COMPUTING MACHINERY PI NEW YORK PA 2 PENN PLAZA, STE 701, NEW YORK, NY 10121-0701 USA SN 0730-0301 J9 ACM T GRAPHIC JI ACM Trans. Graph. PD APR PY 2012 VL 31 IS 2 AR 17 DI 10.1145/2159516.2159523 PG 12 WC Computer Science, Software Engineering SC Computer Science GA 934IJ UT WOS:000303437400006 ER PT J AU Ramaswamy, B Fiskus, W Cohen, B Pellegrino, C Hershman, DL Chuang, E Luu, T Somlo, G Goetz, M Swaby, R Shapiro, CL Stearns, V Christos, P Espinoza-Delgado, I Bhalla, K Sparano, JA AF Ramaswamy, B. Fiskus, W. Cohen, B. Pellegrino, C. Hershman, D. L. Chuang, E. Luu, Thehang Somlo, G. Goetz, M. Swaby, R. Shapiro, C. L. Stearns, V. Christos, P. Espinoza-Delgado, I. Bhalla, K. Sparano, J. A. TI Phase I-II study of vorinostat plus paclitaxel and bevacizumab in metastatic breast cancer: evidence for vorinostat-induced tubulin acetylation and Hsp90 inhibition in vivo SO BREAST CANCER RESEARCH AND TREATMENT LA English DT Article; Proceedings Paper CT 100th Annual Meeting of the American-Association-for-Cancer-Research (AACR) CY APR 18-22, 2009 CL Denver, CO SP Amer Assoc Canc Res (AACR) DE Metastatic breast cancer; Paclitaxel; Bevacizumab; Vorinostat; HDAC inhibitors ID SUBEROYLANILIDE HYDROXAMIC ACID; HISTONE DEACETYLASE INHIBITORS; CELLS; TRIAL; HEAT-SHOCK-PROTEIN-90; HER-2 AB In preclinical models, the histone deacetylase inhibitor vorinostat sensitizes breast cancer cells to tubulin-polymerizing agents and to anti-vascular endothelial growth factor-directed therapies. We sought to determine the safety and efficacy of vorinostat plus paclitaxel and bevacizumab as first-line therapy in metastatic breast cancer (MBC), and the biological effects of vorinostat in vivo. For this purpose of this study, 54 patients with measurable disease and no prior chemotherapy for MBC received vorinostat (200 or 300 mg PO BID) on days 1-3, 8-10, and 15-17, plus paclitaxel (90 mg/m(2)) on days 2, 9, 16, and bevacizumab (10 mg/kg) on days 2 and 16 every 28 days. The primary objective of the phase I study was to determine the recommended phase II dose (RPTD) of vorinostat, and for the phase II to detect an improvement of response rate from 40 to 60% (alpha = 0.10, beta = 0.10). No dose limiting toxicities were observed, and the RPTD of vorinostat was 300 mg BID. For the primary efficacy analysis in 44 patients at the RPTD, we observed 24 objective responses (55%, 95% confidence intervals (C.I) 39%, 70%). The adverse event profile was consistent with paclitaxel-bevacizumab, with the exception of increased diarrhea with the addition of vorinostat. Analysis of serial tumor biopsies in seven patients showed increased acetylation of Hsp90 and alpha-tubulin following vorinostat. Vorinostat induces histone and alpha tubulin acetylation and functional inhibition of Hsp90 in breast cancer in vivo and can be safely combined with paclitaxel and bevacizumab. C1 [Ramaswamy, B.; Shapiro, C. L.] Ohio State Univ, Columbus, OH 43210 USA. [Fiskus, W.; Bhalla, K.] Univ Kansas, Ctr Canc, Kansas City, KS USA. [Cohen, B.; Pellegrino, C.; Sparano, J. A.] Montefiore Med Ctr, Albert Einstein Coll Med, Bronx, NY 10467 USA. [Hershman, D. L.] New York Presbyterian Hosp, New York, NY USA. [Chuang, E.; Christos, P.] Weill Cornell Med Coll, New York, NY USA. [Luu, Thehang; Somlo, G.] City Hope Natl Med Ctr, Duarte, CA 91010 USA. [Goetz, M.] Mayo Clin, Rochester, MN USA. [Swaby, R.] Fox Chase Canc Ctr, Philadelphia, PA 19111 USA. [Stearns, V.] Johns Hopkins, Sidney Kimmel Canc Ctr, Baltimore, MD USA. [Espinoza-Delgado, I.] NCI, Bethesda, MD 20892 USA. RP Ramaswamy, B (reprint author), Ohio State Univ, Columbus, OH 43210 USA. EM Bhuvaneswari.ramaswamy@osumc.edu RI Ramaswamy, Bhuvaneswari/E-3919-2011 FU NCI NIH HHS [N01-CM-62207, N01CM62204, N01-CM-62204, N01 CM62205, N01CM62207, N01 CM062205] NR 26 TC 27 Z9 30 U1 1 U2 11 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0167-6806 J9 BREAST CANCER RES TR JI Breast Cancer Res. Treat. PD APR PY 2012 VL 132 IS 3 SI SI BP 1063 EP 1072 DI 10.1007/s10549-011-1928-x PG 10 WC Oncology SC Oncology GA 933RL UT WOS:000303379800028 PM 22200869 ER PT J AU Patterson, E Webb, R Weisbrod, A Bian, B He, M Zhang, L Holloway, AK Krishna, R Nilubol, N Pacak, K Kebebew, E AF Patterson, E. Webb, R. Weisbrod, A. Bian, B. He, M. Zhang, L. Holloway, A. K. Krishna, R. Nilubol, N. Pacak, K. Kebebew, E. TI The microRNA expression changes associated with malignancy and SDHB mutation in pheochromocytoma SO ENDOCRINE-RELATED CANCER LA English DT Article ID GERMLINE MUTATIONS; GENE-MUTATIONS; PARAGANGLIOMAS; CANCER; HEREDITARY; TARGETS; BENIGN AB Currently, the diagnosis of malignant pheochromocytoma can only be made when there is clinical evidence of metastasis or extensive local invasion. Thus, there is a need for new diagnostic marker(s) to identify tumors with malignant potential. The purpose of this study was to identify microRNAs (miRNAs) that are differentially expressed between benign and malignant pheochromocytomas and assess their diagnostic accuracy. Toward this aim, we analyzed miRNA expression in benign and malignant pheochromocytoma tumor samples using whole genome microarray profiling. Microarray analysis identified eight miRNAs that were significantly differentially expressed between benign and malignant pheochromocytomas. We measured a subset of these miRNAs directly by RT-PCR and found that miR-483-5p, miR-183, and miR-101 had significantly higher expression in malignant tumors as compared to their benign counterparts. Area under the receiver operating curve (AUC) analysis indicated that miR-483-5p, miR-101, and miR-183 could be useful diagnostic markers for distinguishing malignant from benign pheochromocytomas. In addition, these miRNAs could be detected in pheochromocytoma patient serum. Overall our data suggest that misexpression of miR-483-5p, miR-101, and miR-183 is associated with malignant pheochromocytoma. Endocrine-Related Cancer (2012) 19 157-166 C1 [Patterson, E.; Webb, R.; Weisbrod, A.; Bian, B.; He, M.; Zhang, L.; Krishna, R.; Nilubol, N.; Kebebew, E.] NCI, Endocrine Oncol Sect, Surg Branch, NIH,Hatfield Clin Res Ctr, Bethesda, MD 20892 USA. [Holloway, A. K.] Univ Calif San Francisco, Gladstone Inst, San Francisco, CA 94158 USA. [Pacak, K.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Program Reprod & Adult Endocrinol, NIH, Bethesda, MD 20892 USA. RP Kebebew, E (reprint author), NCI, Endocrine Oncol Sect, Surg Branch, NIH,Hatfield Clin Res Ctr, Room 4-5952,10 Ctr Dr, Bethesda, MD 20892 USA. EM kebebewe@mail.nih.gov RI Holloway, Alisha/H-9574-2013 OI Holloway, Alisha/0000-0001-9810-389X 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 23 TC 22 Z9 24 U1 1 U2 3 PU BIOSCIENTIFICA LTD PI BRISTOL PA EURO HOUSE, 22 APEX COURT WOODLANDS, BRADLEY STOKE, BRISTOL BS32 4JT, ENGLAND SN 1351-0088 J9 ENDOCR-RELAT CANCER JI Endocr.-Relat. Cancer PD APR PY 2012 VL 19 IS 2 BP 157 EP 166 DI 10.1530/ERC-11-0308 PG 10 WC Oncology; Endocrinology & Metabolism SC Oncology; Endocrinology & Metabolism GA 935SE UT WOS:000303539700008 PM 22241719 ER PT J AU Valent, P Gleich, GJ Reiter, A Roufosse, F Weller, PF Hellmann, A Metzgeroth, G Leiferman, KM Arock, M Sotlar, K Butterfield, JH Cerny-Reiterer, S Mayerhofer, M Vandenberghe, P Haferlach, T Bochner, BS Gotlib, J Horny, HP Simon, HU Klion, AD AF Valent, Peter Gleich, Gerald J. Reiter, Andreas Roufosse, Florence Weller, Peter F. Hellmann, Andrzej Metzgeroth, Georgia Leiferman, Kristin M. Arock, Michel Sotlar, Karl Butterfield, Joseph H. Cerny-Reiterer, Sabine Mayerhofer, Matthias Vandenberghe, Peter Haferlach, Torsten Bochner, Bruce S. Gotlib, Jason Horny, Hans-Peter Simon, Hans-Uwe Klion, Amy D. TI Pathogenesis and classification of eosinophil disorders: a review of recent developments in the field SO EXPERT REVIEW OF HEMATOLOGY LA English DT Review DE classification; eosinophilic leukemia; FIP1L1-PDGFRA; hypereosinophilia; hypereosinophilic syndromes; targeted therapy ID IDIOPATHIC HYPEREOSINOPHILIC SYNDROME; HUMAN PERIPHERAL-BLOOD; VASCULAR ENDOTHELIAL-CELLS; GROWTH-FACTOR RECEPTOR; CHURG-STRAUSS-SYNDROME; CHRONIC MYELOPROLIFERATIVE DISEASES; RECOMBINANT HUMAN INTERLEUKIN-5; COLONY-STIMULATING FACTOR; MAJOR BASIC-PROTEIN; IN-VITRO AB Eosinophils and their products play an essential role in the pathogenesis of various reactive and neoplastic disorders. Depending on the underlying disease, molecular defect and involved cytokines, hypereosinophilia may develop and may lead to organ damage. In other patients, persistent eosinophilia is accompanied by typical clinical findings, but the causative role and impact of eosinophilia remain uncertain. For patients with eosinophil-mediated organ pathology, early therapeutic intervention with agents reducing eosinophil counts can be effective in limiting or preventing irreversible organ damage. Therefore, it is important to approach eosinophil disorders and related syndromes early by using established criteria, to perform all appropriate staging investigations, and to search for molecular targets of therapy. In this article, we review current concepts in the pathogenesis and evolution of eosinophilia and eosinophil-related organ damage in neoplastic and non-neoplastic conditions. In addition, we discuss classifications of eosinophil disorders and related syndromes as well as diagnostic algorithms and standard treatment for various eosinophil-related disorders. C1 [Valent, Peter; Cerny-Reiterer, Sabine] Med Univ Vienna, Dept Med 1, Div Hematol & Hemostaseol, Vienna, Austria. [Valent, Peter; Cerny-Reiterer, Sabine] Ludwig Boltzmann Cluster Oncol, Vienna, Austria. [Gleich, Gerald J.; Leiferman, Kristin M.] Univ Utah, Dept Dermatol, Salt Lake City, UT USA. [Reiter, Andreas; Metzgeroth, Georgia] Univ Med Mannheim, Med Univ Klin, Mannheim, Germany. [Roufosse, Florence] Univ Libre Brussels, Dept Internal Med, Erasme Hosp, Brussels, Belgium. [Weller, Peter F.] Harvard Univ, Beth Israel Deaconess Med Ctr, Sch Med, Boston, MA 02215 USA. [Hellmann, Andrzej] Med Univ Gdansk, Dept Hematol, Gdansk, Poland. [Arock, Michel] Ecole Normale Super, LBPA, CNRS, UMR8113, Cachan, France. [Sotlar, Karl; Horny, Hans-Peter] Univ Munich, Inst Pathol, D-8000 Munich, Germany. [Butterfield, Joseph H.] Mayo Clin Rochester, Div Allerg Dis, Rochester, MN USA. [Mayerhofer, Matthias] Med Univ Vienna, Dept Lab Med, Vienna, Austria. [Vandenberghe, Peter] Katholieke Univ Leuven, Ctr Human Genet, Louvain, Belgium. [Vandenberghe, Peter] Univ Hosp Leuven, Louvain, Belgium. [Haferlach, Torsten] MLL Munchner Leukamielab, Munich, Germany. [Bochner, Bruce S.] Johns Hopkins Univ, Sch Med, Dept Med, Div Allergy & Clin Immunol, Baltimore, MD 21205 USA. [Gotlib, Jason] Stanford Univ, Sch Med, Stanford Canc Ctr, Stanford, CA 94305 USA. [Simon, Hans-Uwe] Univ Bern, Inst Pharmacol, CH-3012 Bern, Switzerland. [Klion, Amy D.] NIAID, Eosinophil Pathol Unit, Parasit Dis Lab, NIH, Bethesda, MD 20892 USA. RP Valent, P (reprint author), Med Univ Vienna, Dept Med 1, Div Hematol & Hemostaseol, Vienna, Austria. EM peter.valent@meduniwien.ac.at OI Vandenberghe, Peter/0000-0003-4719-1935; Simon, Hans-Uwe/0000-0002-9404-7736; Klion, Amy/0000-0002-4986-5326 FU Novartis; BMS; NIAID, NIH; GSK; Medical University of Vienna; Division of Intramural Research, NIAID, NIH, Bethesda, MD, USA FX P Valent has received a Research Grant from Novartis and a Research Grant from BMS, as well as honoraria from Novartis and BMS. AD Klein is supported by the Intramural Program of the NIAID, NIH. KM Leiferman, HU Simon and GJ Gleich have been supported by grants from GSK. M Arock received honorarium from Novartis. P Vandenberghe is a Senior Clinical Investigator of FWO-Vlaanderen. T Haferlach is part owner of the Munich Leukemia Laboratory. A Reiter received Honoraria from Novartis and BMS. BS Bochner is a co-author on existing and pending Siglec-8-related patents. If Siglec-8-related products are developed in the future, BS Bochner may be entitled to a share of royalties received by Johns Hopkins University on the potential sales of such products. The terms of this arrangement are being managed by Johns Hopkins University in accordance with its conflict of interest policies. This study was supported by a research grant of the Medical University of Vienna and by the Division of Intramural Research, NIAID, NIH, Bethesda, MD, USA. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed. NR 182 TC 52 Z9 52 U1 0 U2 7 PU EXPERT REVIEWS PI LONDON PA UNITEC HOUSE, 3RD FL, 2 ALBERT PLACE, FINCHLEY CENTRAL, LONDON N3 1QB, ENGLAND SN 1747-4086 J9 EXPERT REV HEMATOL JI Expert Rev. Hematol. PD APR PY 2012 VL 5 IS 2 BP 157 EP 176 DI 10.1586/EHM.11.81 PG 20 WC Hematology SC Hematology GA 936ZS UT WOS:000303629400013 PM 22475285 ER PT J AU Sincan, M Simeonov, DR Adams, D Markello, TC Pierson, TM Toro, C Gahl, WA Boerkoel, CF AF Sincan, Murat Simeonov, Dimitre R. Adams, David Markello, Thomas C. Pierson, Tyler M. Toro, Camilo Gahl, William A. Boerkoel, Cornelius F. CA NIH Undiagnosed Dis Program TI VAR-MD: A tool to analyze whole exome-genome variants in small human pedigrees with mendelian inheritance SO HUMAN MUTATION LA English DT Article DE exome; next generation sequencing; variant filtering; Mendelian ID MUTATIONS; FORM; DISEASES; GENE AB The analysis of variants generated by exome sequencing (ES) of families with rare Mendelian diseases is a time-consuming, manual process that represents one barrier to applying the technology routinely. To address this issue, we have developed a software tool, VAR-MD (), for analyzing the DNA sequence variants produced by human ES. VAR-MD generates a ranked list of variants using predicted pathogenicity, Mendelian inheritance models, genotype quality, and population variant frequency data. VAR-MD was tested using two previously solved data sets and one unsolved data set. In the solved cases, the correct variant was listed at the top of VAR-MD's variant ranking. In the unsolved case, the correct variant was highly ranked, allowing for subsequent identification and validation. We conclude that VAR-MD has the potential to enhance mutation identification using family based, annotated next generation sequencing data. Moreover, we predict an incremental advancement in software performance as the reference databases, such as Single Nucleotide Polymorphism Database and Human Gene Mutation Database, continue to improve. Hum Mutat 33:593598, 2012. (c) 2012 Wiley Periodicals, Inc.* This article is a US Government work and, as such, is in the public domain of the United States of America. C1 [Sincan, Murat; Adams, David; Pierson, Tyler M.; Gahl, William A.] NHGRI, Med Genet Branch, NIH, Bethesda, MD 20892 USA. [Markello, Thomas C.; Gahl, William A.] NHGRI, Off Clin Director, NIH, Bethesda, MD 20892 USA. [Simeonov, Dimitre R.; Adams, David; Markello, Thomas C.; Toro, Camilo; Gahl, William A.; Boerkoel, Cornelius F.] NIH, Undiagnosed Dis Program, Bethesda, MD 20892 USA. [Pierson, Tyler M.] Childrens Natl Med Ctr, Dept Neurol, Washington, DC 20010 USA. [Pierson, Tyler M.] NINDS, Neurogenet Branch, Bethesda, MD 20892 USA. RP Sincan, M (reprint author), NHGRI, Med Genet Branch, NIH, 10 Ctr Dr,MSC 1851,Bldg 10,Room 3C-716, Bethesda, MD 20892 USA. EM sincanm@mail.nih.gov FU Office of Rare Diseases Research; NIH Clinical Center; National Human Genome Research Institute; National Institute of Neurological Disorders and Stroke FX Contract grant sponsors: Office of Rare Diseases Research (Dr. Stephen Groft); the NIH Clinical Center ( Dr. John Gallin); and the Intramural Research Programs of the National Human Genome Research Institute and the National Institute of Neurological Disorders and Stroke. NR 32 TC 19 Z9 19 U1 0 U2 1 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1059-7794 J9 HUM MUTAT JI Hum. Mutat. PD APR PY 2012 VL 33 IS 4 BP 593 EP 598 DI 10.1002/humu.22034 PG 6 WC Genetics & Heredity SC Genetics & Heredity GA 906IP UT WOS:000301338900004 PM 22290570 ER PT J AU Adams, DR Sincan, M Fajardo, KF Mullikin, JC Pierson, TM Toro, C Boerkoel, CF Tifft, CJ Gahl, WA Markello, TC AF Adams, David R. Sincan, Murat Fajardo, Karin Fuentes Mullikin, James C. Pierson, Tyler M. Toro, Camilo Boerkoel, Cornelius F. Tifft, Cynthia J. Gahl, William A. Markello, Tom C. CA NIH Undiagnosed Dis Program TI Analysis of DNA sequence variants detected by high-throughput sequencing SO HUMAN MUTATION LA English DT Article DE genomics; next generation sequencing; exome; molecular diagnosis ID AMINO-ACID SUBSTITUTIONS; SPLICE-SITE PREDICTION; UNDIAGNOSED DISEASES; PROTEIN FAMILIES; GENOME ANALYSIS; MESSENGER-RNA; HEARING-LOSS; MUTATIONS; DATABASE; GENE AB The Undiagnosed Diseases Program at the National Institutes of Health uses high-throughput sequencing (HTS) to diagnose rare and novel diseases. HTS techniques generate large numbers of DNA sequence variants, which must be analyzed and filtered to find candidates for disease causation. Despite the publication of an increasing number of successful exome-based projects, there has been little formal discussion of the analytic steps applied to HTS variant lists. We present the results of our experience with over 30 families for whom HTS sequencing was used in an attempt to find clinical diagnoses. For each family, exome sequence was augmented with high-density SNP-array data. We present a discussion of the theory and practical application of each analytic step and provide example data to illustrate our approach. The article is designed to provide an analytic roadmap for variant analysis, thereby enabling a wide range of researchers and clinical genetics practitioners to perform direct analysis of HTS data for their patients and projects. Hum Mutat 33:599608, 2012. (c) 2012 Wiley Periodicals, Inc. C1 [Adams, David R.; Sincan, Murat; Gahl, William A.] NHGRI, Med Genet Branch, NIH, Bethesda, MD 20892 USA. [Adams, David R.; Fajardo, Karin Fuentes; Pierson, Tyler M.; Toro, Camilo; Boerkoel, Cornelius F.; Tifft, Cynthia J.; Gahl, William A.] NIH, Undiagnosed Dis Program, Bethesda, MD 20892 USA. [Tifft, Cynthia J.; Gahl, William A.; Markello, Tom C.] NHGRI, Off Clin Director, NIH, Bethesda, MD 20892 USA. [Pierson, Tyler M.] NINDS, Neurogenet Branch, NIH, Bethesda, MD 20892 USA. [Mullikin, James C.] NHGRI, Intramural Sequencing Ctr, NIH, Bethesda, MD 20892 USA. RP Adams, DR (reprint author), NHGRI, Med Genet Branch, NIH, 10 Ctr Dr,MSC 1851,10-10C-103, Bethesda, MD 20892 USA. EM david.adams@nih.gov FU Intramural division of the National Human Genome Research Institute; National Institute of Neurological Disorders and Stroke; NIH Clinical Center; NIH Office of the Director FX Contract grant sponsors: Intramural division of the National Human Genome Research Institute; the National Institute of Neurological Disorders and Stroke; the NIH Clinical Center; and the NIH Office of the Director. NR 70 TC 21 Z9 21 U1 1 U2 7 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1059-7794 J9 HUM MUTAT JI Hum. Mutat. PD APR PY 2012 VL 33 IS 4 BP 599 EP 608 DI 10.1002/humu.22035 PG 10 WC Genetics & Heredity SC Genetics & Heredity GA 906IP UT WOS:000301338900005 PM 22290882 ER PT J AU Fajardo, KVF Adams, D Mason, CE Sincan, M Tifft, C Toro, C Boerkoel, CF Gahl, W Markello, T AF Fajardo, Karin V. Fuentes Adams, David Mason, Christopher E. Sincan, Murat Tifft, Cynthia Toro, Camilo Boerkoel, Cornelius F. Gahl, William Markello, Thomas CA NISC Comparative Sequencing NIH Undiagnosed Dis Program TI Detecting false-positive signals in exome sequencing SO HUMAN MUTATION LA English DT Article DE Exome sequencing; inherited disease; false positives; next generation sequencing; genomics; Illumina; sequencing errors; alignment errors; WES; SureSelect Human All Exon ID HARDY-WEINBERG EQUILIBRIUM; UNDIAGNOSED DISEASES; EXACT TESTS; MUTATIONS; GENOME; ACCURATE; GENE; CHALLENGES; DISCOVERY; ALIGNMENT AB Disease gene discovery has been transformed by affordable sequencing of exomes and genomes. Identification of disease-causing mutations requires sifting through a large number of sequence variants. A subset of the variants are unlikely to be good candidates for disease causation based on one or more of the following criteria: (1) being located in genomic regions known to be highly polymorphic, (2) having characteristics suggesting assembly misalignment, and/or (3) being labeled as variants based on misleading reference genome information. We analyzed exome sequence data from 118 individuals in 29 families seen in the NIH Undiagnosed Diseases Program (UDP) to create lists of variants and genes with these characteristics. Specifically, we identified several groups of genes that are candidates for provisional exclusion during exome analysis: 23,389 positions with excess heterozygosity suggestive of alignment errors and 1,009 positions in which the hg18 human genome reference sequence appeared to contain a minor allele. Exclusion of such variants, which we provide in supplemental lists, will likely enhance identification of disease-causing mutations using exome sequence data. Hum Mutat 33:609613, 2012. (c) 2012 Wiley Periodicals, Inc. C1 [Markello, Thomas] NHGRI, Med Genet Branch, Off Clin Director, NIH, Bethesda, MD 20892 USA. [Fajardo, Karin V. Fuentes; Adams, David; Tifft, Cynthia; Toro, Camilo; Boerkoel, Cornelius F.; Gahl, William] NIH Off Rare Dis Res, NIH Undiagnosed Dis Program, Bethesda, MD USA. [NISC Comparative Sequencing] NIH, Intramural Sequencing Ctr, Bethesda, MD 20892 USA. [Mason, Christopher E.] Cornell Univ, Weill Med Coll, Dept Physiol & Biophys, New York, NY 10021 USA. [Mason, Christopher E.] Cornell Univ, Weill Med Coll, HRH Prince Alwaleed Bin Talal Bin Abdulaziz Alsau, New York, NY 10021 USA. RP Markello, T (reprint author), NHGRI, Med Genet Branch, Off Clin Director, NIH, 10 Ctr Dr,Bldg 10-10C103, Bethesda, MD 20892 USA. EM markellot@mail.nih.gov FU NHGRI; UDP through the office of the Director NIH FX Contract grant sponsors: NHGRI intramural funding; UDP program through the office of the Director NIH. NR 48 TC 50 Z9 50 U1 0 U2 2 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1059-7794 EI 1098-1004 J9 HUM MUTAT JI Hum. Mutat. PD APR PY 2012 VL 33 IS 4 BP 609 EP 613 DI 10.1002/humu.22033 PG 5 WC Genetics & Heredity SC Genetics & Heredity GA 906IP UT WOS:000301338900006 ER PT J AU Dias, C Sincan, M Cherukuri, PF Rupps, R Huang, Y Briemberg, H Selby, K Mullikin, JC Markello, TC Adams, DR Gahl, WA Boerkoel, CF AF Dias, Cristina Sincan, Murat Cherukuri, Praveen F. Rupps, Rosemarie Huang, Yan Briemberg, Hannah Selby, Kathryn Mullikin, James C. Markello, Thomas C. Adams, David R. Gahl, William A. Boerkoel, Cornelius F. TI An analysis of exome sequencing for diagnostic testing of the genes associated with muscle disease and spastic paraplegia SO HUMAN MUTATION LA English DT Review DE CAPN3; exome; LGMD; HSP; neuromuscular disorders; clinical genetic testing ID CONGENITAL MUSCULAR-DYSTROPHY; FIBER-TYPE DISPROPORTION; INCLUSION-BODY MYOPATHY; HEREDITARY HEARING-LOSS; X-LINKED GENE; NEMALINE MYOPATHY; BINDING-PROTEIN; ABNORMAL GLYCOSYLATION; CENTRONUCLEAR MYOPATHY; DILATED CARDIOMYOPATHY AB In this study, we assess exome sequencing (ES) as a diagnostic alternative for genetically heterogeneous disorders. Because ES readily identified a previously reported homozygous mutation in the CAPN3 gene for an individual with an undiagnosed limb girdle muscular dystrophy, we evaluated ES as a generalizable clinical diagnostic tool by assessing the targeting efficiency and sequencing coverage of 88 genes associated with muscle disease (MD) and spastic paraplegia (SPG). We used three exome-capture kits on 125 individuals. Exons constituting each gene were defined using the UCSC and CCDS databases. The three exome-capture kits targeted 4792% of bases within the UCSC-defined exons and 9799% of bases within the CCDS-defined exons. An average of 61.299.5% and 19.199.5% of targeted bases per gene were sequenced to 20X coverage within the CCDS-defined MD and SPG coding exons, respectively. Greater than 9599% of targeted known mutation positions were sequenced to =1X coverage and 5587% to =20X coverage in every exome. We conclude, therefore, that ES is a rapid and efficient first-tier method to screen for mutations, particularly within the CCDS annotated exons, although its application requires disclosure of the extent of coverage for each targeted gene and supplementation with second-tier Sanger sequencing for full coverage. Hum Mutat 33:614626, 2012. (c) 2012 Wiley Periodicals, Inc. C1 [Boerkoel, Cornelius F.] NHGRI, UDP Translat Lab, NIH, Bethesda, MD 20892 USA. [Dias, Cristina; Rupps, Rosemarie; Boerkoel, Cornelius F.] Univ British Columbia, Dept Med Genet, Vancouver, BC, Canada. [Dias, Cristina; Rupps, Rosemarie; Boerkoel, Cornelius F.] Childrens & Womens Hlth Ctr British Columbia, Child & Family Res Inst, Vancouver, BC, Canada. [Briemberg, Hannah] Univ British Columbia, Dept Med, Div Neurol, Vancouver, BC V6T 1W5, Canada. [Selby, Kathryn] Univ British Columbia, Dept Pediat, Div Pediat Neurol, Vancouver, BC V6T 1W5, Canada. [Mullikin, James C.] NHGRI, NIH, Intramural Sequencing Ctr, Bethesda, MD 20892 USA. [Sincan, Murat; Cherukuri, Praveen F.; Huang, Yan; Markello, Thomas C.; Adams, David R.; Gahl, William A.] NIH, Undiagnosed Dis Program, Bethesda, MD 20892 USA. RP Boerkoel, CF (reprint author), NHGRI, UDP Translat Lab, NIH, 9 Mem Dr,Bldg 9,Rm 1E100, Bethesda, MD 20892 USA. EM boerkoelcf@mail.nih.gov OI Selby, Kathryn/0000-0001-9239-1704; Dias, Cristina/0000-0001-5411-4984 FU Rare Disease Foundation; National Human Genome Research Institute; Child and Family Research Institute; Canadian Child Health Clinician Scientist Program FX Contract grant sponsors: This study was supported in part by the Rare Disease Foundation and by the Intramural Research Program of the National Human Genome Research Institute. CD is funded by the Child and Family Research Institute and the Canadian Child Health Clinician Scientist Program. NR 117 TC 22 Z9 22 U1 0 U2 4 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1059-7794 J9 HUM MUTAT JI Hum. Mutat. PD APR PY 2012 VL 33 IS 4 BP 614 EP 626 DI 10.1002/humu.22032 PG 13 WC Genetics & Heredity SC Genetics & Heredity GA 906IP UT WOS:000301338900007 PM 22311686 ER PT J AU Mou, HW Li, ZM Kong, Y Deng, B Qian, LH Wang, JM Le, YY AF Mou, Haiwei Li, Zongmeng Kong, Yan Deng, Bo Qian, Lihua Wang, Ji Ming Le, Yingying TI Proinflammatory Stimulants Promote the Expression of a Promiscuous G Protein-Coupled Receptor, mFPR2, in Microvascular Endothelial Cells SO INFLAMMATION LA English DT Article DE lipopolysaccharide; interleukin-1 beta; murine formylpeptide receptor 2; endothelial cell; MAP kinase; NF-kappa B ID FORMYL-PEPTIDE RECEPTOR; CEREBRAL-AMYLOID-ANGIOPATHY; MURINE MICROGLIAL CELLS; SIGNAL-TRANSDUCTION; DENDRITIC CELLS; UP-REGULATION; MATRIX-METALLOPROTEINASE-9; ANGIOGENESIS; INFLAMMATION; MACROPHAGES AB Human formylpeptide receptor 2 (FPR2) and its mouse homologue mFPR2 belong to the G protein-coupled, seven-transmembrane receptor superfamily. Both FPR2 and mFPR2 recognize a variety of exogenous and host-derived chemotactic peptides associated with proinflammatory conditions. Since endothelial cells actively participate in inflammation, we investigated whether microvascular endothelial cells express mFPR2 and its regulation by proinflammatory factors. We found that resting primary mouse microvascular endothelial cells and a cell line bEnd.3 expressed low levels of mFPR2 at both mRNA and protein levels, which was markedly enhanced by two key proinflammatory stimulants, lipopolysaccharide (LPS) and interleukin (IL)-1 beta. While the inductive effect of LPS was dependent on the JNK MAP kinase, both JNK and ERK MAP kinases were utilized by IL-1 beta to enhance mFPR2 expression. Overexpression of dominant-negative I kappa B alpha attenuated LPS- and IL-1 beta-induced mFPR2 expression, indicating an essential role for NF-kappa B in regulating mFPR2 expression in endothelial cells by proinflammatory stimulants. Our results suggest that upregulated mFPR2 in vascular endothelial cells under inflammatory conditions may mediate cell responses in diseases in which mFPR2 agonists are elevated. C1 [Mou, Haiwei; Li, Zongmeng; Kong, Yan; Deng, Bo; Qian, Lihua; Le, Yingying] Chinese Acad Sci, Shanghai Inst Biol Sci, Inst Nutr Sci, Key Lab Nutr & Metab, Shanghai, Peoples R China. [Wang, Ji Ming] Natl Canc Inst Frederick, Mol Immunoregulat Lab, Canc & Inflammat Program, Ctr Canc Res, Frederick, MD USA. [Mou, Haiwei; Li, Zongmeng; Kong, Yan; Deng, Bo; Qian, Lihua; Le, Yingying] Chinese Acad Sci, Grad Sch, Shanghai, Peoples R China. RP Le, YY (reprint author), Chinese Acad Sci, Shanghai Inst Biol Sci, Inst Nutr Sci, Key Lab Nutr & Metab, Shanghai, Peoples R China. EM yyle@sibs.ac.cn FU National Basic Research Program of China (973 Program) [2010CB529701]; Science and Technology Commission of Shanghai Municipality [09ZR1436700]; National Natural Science Foundation of China [30870931] FX We thank R. Lin (McGill University, Montreal, QC, Canada) for providing plasmid DN-I kappa B alpha and control vector flag-zeo, and M. Li (Sun Yat-sen University, Guangzhou, China) for providing plasmid c-Jun DN. This work was supported by research grants from: the National Basic Research Program of China (973 Program) (2010CB529701); the Science and Technology Commission of Shanghai Municipality (09ZR1436700), and the National Natural Science Foundation of China (30870931) to Y. Le. NR 31 TC 3 Z9 4 U1 0 U2 4 PU SPRINGER/PLENUM PUBLISHERS PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0360-3997 J9 INFLAMMATION JI Inflammation PD APR PY 2012 VL 35 IS 2 BP 656 EP 664 DI 10.1007/s10753-011-9358-9 PG 9 WC Cell Biology; Immunology SC Cell Biology; Immunology GA 933SG UT WOS:000303382200030 PM 21761148 ER PT J AU Singh, GK Siahpush, M Williams, SD AF Singh, Gopal K. Siahpush, Mohammad Williams, Shanita D. TI Changing Urbanization Patterns in US Lung Cancer Mortality, 1950-2007 SO JOURNAL OF COMMUNITY HEALTH LA English DT Article DE Urbanization; Metropolitan; Nonmetropolitan; Lung cancer mortality; Deprivation; Age; Sex; Time trend ID AREA SOCIOECONOMIC PATTERNS; INEQUALITIES; DEPRIVATION AB This study examined disparities in lung cancer mortality rates among US men and women in metropolitan and non-metropolitan areas from 1950 through 2007. Annual age-adjusted mortality rates were calculated for men and women in metropolitan and non-metropolitan areas, and differences in mortality rates were tested for statistical significance. Log-linear regression was used to model annual rates of change in mortality over time, while Poisson regression was used to estimate relative risk after adjusting for age, sex, deprivation, and urbanization levels. Urbanization patterns in lung cancer mortality changed dramatically between 1950 and 2007. Compared to men in metropolitan areas, men aged 25-64 years in non-metropolitan areas had significantly lower lung cancer mortality rates from 1950 to 1977 and men aged >= 65 years in non-metropolitan areas had lower mortality rates from 1950 to 1985. Differentials began to reverse and widen by the mid-1980s for men and by the mid-1990s for younger women. In 2007, compared to their metropolitan counterparts, men aged 25-64 and >= 65 years in non-metropolitan areas had 49 and 19% higher lung cancer mortality and women aged 25-64 and >= 65 years in non-metropolitan areas had 32 and 4% higher lung cancer mortality, respectively. Although adjustment for deprivation levels reduced excess lung cancer mortality risk among those in non-metropolitan areas, significant rural-urban differences remained. Rural-urban patterns reversed because of faster and earlier reductions in lung cancer mortality among men and women in metropolitan areas. Temporal trends in rural-urban disparities in lung cancer mortality appear to be consistent with those in smoking. C1 [Singh, Gopal K.] Maternal & Child Hlth Bur, US Dept HHS, Hlth Resources & Serv Adm, Rockville, MD 20857 USA. [Siahpush, Mohammad] Univ Nebraska Med Ctr, Dept Hlth Promot Social & Behav Hlth, Omaha, NE 68198 USA. [Williams, Shanita D.] Natl Inst Minor Hlth & Hlth Dispar, NIH, Bethesda, MD 20892 USA. RP Singh, GK (reprint author), Maternal & Child Hlth Bur, US Dept HHS, Hlth Resources & Serv Adm, 5600 Fishers Lane,Room 18-41, Rockville, MD 20857 USA. EM gsingh@hrsa.gov; msiahpush@unmc.edu; shanita@mail.nih.gov NR 26 TC 10 Z9 10 U1 1 U2 8 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0094-5145 J9 J COMMUN HEALTH JI J. Community Health PD APR PY 2012 VL 37 IS 2 BP 412 EP 420 DI 10.1007/s10900-011-9458-3 PG 9 WC Health Policy & Services; Public, Environmental & Occupational Health SC Health Care Sciences & Services; Public, Environmental & Occupational Health GA 936KY UT WOS:000303590500020 PM 21858690 ER PT J AU Abdoler, E Wendler, D AF Abdoler, Emily Wendler, David TI USING DATA TO IMPROVE SURROGATE CONSENT FOR CLINICAL RESEARCH WITH INCAPACITATED ADULTS SO JOURNAL OF EMPIRICAL RESEARCH ON HUMAN RESEARCH ETHICS LA English DT Article DE capacity; consent; research ID RESEARCH ADVANCE DIRECTIVES; DEMENTIA RESEARCH; RESEARCH PARTICIPATION; ALZHEIMERS-DISEASE; INFORMED CONSENT; DECISION-MAKERS; PROXY CONSENT; CARE RESEARCH; PREFERENCES; WILLINGNESS AB CURRENT PRACTICE RELIES ON surrogates to enroll incapacitated adults in research. Yet, it is unclear to what extent this practice protects adults who have lost the ability to consent for themselves. To address this question, we conducted two literature searches to identify articles which report empirical data on three issues central to protecting adults who have lost the ability to consent: (1) adults' willingness to participate in research should they lose the ability to consent; (2) adults' willingness to allow a surrogate to make research decisions for them; and (3) the extent to which surrogates' enrollment decisions are consistent with their charges' preferences and values. These searches identified 21 articles, representing 20 distinct datasets. The data indicate that many adults are willing to participate in research should they lose the ability to consent, and many are willing to allow their family members to make research decisions for them if they become incapacitated. The data also raise concern that surrogates may be making research enrollment decisions that, in some cases, are inconsistent with their charges' preferences and values. These findings suggest that modifications to current practice should be considered to better protect adults who have lost the ability to consent. One option would be to require, in addition to surrogate permission and subject assent, sufficient evidence that enrollment is consistent with the individual's preferences and values. C1 [Wendler, David] NIH, Dept Bioeth, Ctr Clin, Bethesda, MD 20892 USA. RP Wendler, D (reprint author), NIH, Dept Bioeth, Ctr Clin, Bldg 10,Room 1C118, Bethesda, MD 20892 USA. EM dwendler@nih.gov FU NIH FX Thanks to Marion Danis, NIH, Annette Rid, NIH, and Rebecca Wolitz, NIH, for their helpful comments on previous drafts of the manuscript; to Seema Shah, NIH, for her important input; and to Karen Smith MLS, NIH Library, for assistance with the literature search. This research was supported by the Intramural Research Program of the NIH. NR 33 TC 3 Z9 3 U1 0 U2 0 PU UNIV CALIFORNIA PRESS PI BERKELEY PA C/O JOURNALS & DIGITAL PUBLISHING DIVISION, 2000 CENTER ST, STE 303, BERKELEY, CA 94704-1223 USA SN 1556-2646 J9 J EMPIR RES HUM RES JI J. Empir. Res. Hum. Res. Ethics PD APR PY 2012 VL 7 IS 2 BP 37 EP 50 DI 10.1525/jer.2012.7.2.37 PG 14 WC Ethics; Medical Ethics SC Social Sciences - Other Topics; Medical Ethics GA 937CW UT WOS:000303637600005 PM 22565582 ER PT J AU Fraum, TJ Barak, S Pack, S Lonser, RR Fine, HA Quezado, M Iwamoto, FM AF Fraum, Tyler J. Barak, Stephanie Pack, Svetlana Lonser, Russell R. Fine, Howard A. Quezado, Martha Iwamoto, Fabio M. TI Spinal cord glioneuronal tumor with neuropil-like islands with 1p/19q deletion in an adult with low-grade cerebral oligodendroglioma SO JOURNAL OF NEURO-ONCOLOGY LA English DT Article DE Glioneuronal tumor with neuropil-like islands (GTNI); 1p/19q deletion; Oligodendroglioma; Astrocytoma ID GLIOMAS; FEATURES; NODULES; 19Q; 1P AB Glioneuronal tumor with neuropil-like islands (GTNI) is considered a rare variant of astrocytoma, characterized by discrete aggregates of cells expressing neuronal markers that punctuate a GFAP-positive glial background. Of the 24 published GTNI cases, only two occurred in adult spinal cords; none occurred concurrent with another CNS tumor; and none of those tested exhibited the 1p/19q deletion typical of oligodendroglioma. A 48-year-old man without significant past medical history was diagnosed with a WHO grade II oligodendroglioma by stereotactic biopsy of a lesion discovered after the patient suffered a generalized tonic-clonic seizure. By FISH analysis, this tumor exhibited the 1p/19q deletion present in up to 80% of oligodendrogliomas. The patient received 14 monthly cycles of temozolomide, and his cerebral tumor had a minor response. When the patient subsequently reported progressive paresthesias of his lower extremities, an MRI revealed an enhancing, cystic tumor of the thoracic spinal cord that was diagnosed as GTNI by histological analysis. By FISH analysis, this lesion exhibited the same 1p/19q deletion present in the concurrent cerebral oligodendroglioma. This case of a spinal cord GTNI with 1p/19q deletions constitutes the third report of a spinal cord GTNI in an adult patient; the first report of a GTNI in an individual with a separate CNS neoplasm; and the first report of a GTNI with 1p/19q deletions. This case establishes a potential genetic kinship between GTNI and oligodendroglioma that warrants further investigation. C1 [Fraum, Tyler J.; Fine, Howard A.; Iwamoto, Fabio M.] NIH, Neurooncol Branch, Bethesda, MD 20892 USA. [Fraum, Tyler J.] Duke Univ, Sch Med, Durham, NC USA. [Barak, Stephanie; Pack, Svetlana; Quezado, Martha] NCI, Pathol Lab, NIH, Bethesda, MD 20892 USA. [Lonser, Russell R.] Natl Inst Neurol Disorders & Stroke, Surg Neurol Branch, NIH, Bethesda, MD 20892 USA. RP Iwamoto, FM (reprint author), NIH, Neurooncol Branch, 9030 Old Georgetown Rd,Room 221, Bethesda, MD 20892 USA. EM tyler.fraum@duke.edu; stephanie.barak@nih.gov; spack@mail.nih.gov; lonserr@ninds.nih.gov; hfine@mail.nih.gov; quezadom@mail.nih.gov; iwamotofm@mail.nih.gov RI Pack, Svetlana/C-2020-2014 FU NIH [1ZIABC011347-01, 1ZIABC011348-01]; Pfizer Inc; National Cancer Institute FX NIH Intramural Research Program (1ZI-DBC011098-02). T.J.F. is a Fellow in the Clinical Research Training Program, a public-private partnership supported jointly by the NIH and Pfizer Inc (via a grant to the Foundation for NIH from Pfizer Inc). F. M. I. is supported by the National Cancer Institute's Clinical Investigator Development Program and the NIH Intramural Program (1ZIABC011347-01 and 1ZIABC011348-01). NR 23 TC 5 Z9 7 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0167-594X J9 J NEURO-ONCOL JI J. Neuro-Oncol. PD APR PY 2012 VL 107 IS 2 BP 421 EP 426 DI 10.1007/s11060-011-0760-9 PG 6 WC Oncology; Clinical Neurology SC Oncology; Neurosciences & Neurology GA 934TG UT WOS:000303469000024 PM 22083647 ER PT J AU Obregon, D Hou, HY Deng, J Giunta, B Tian, J Darlington, D Shahaduzzaman, M Zhu, YY Mori, T Mattson, MP Tan, J AF Obregon, Demian Hou, Huayan Deng, Juan Giunta, Brian Tian, Jun Darlington, Donna Shahaduzzaman, Md Zhu, Yuyuan Mori, Takashi Mattson, Mark P. Tan, Jun TI Soluble amyloid precursor protein-alpha modulates beta-secretase activity and amyloid-beta generation SO NATURE COMMUNICATIONS LA English DT Article ID ALZHEIMERS-DISEASE; GAMMA-SECRETASE; OXIDATIVE STRESS; CLEAVING ENZYME; CHRONIC HYPOXIA; A-BETA; BACE1; APP; CLEAVAGE; MICE AB In sporadic age-related forms of Alzheimer's disease (AD), it is unclear why amyloid-beta (A beta) peptides accumulate. Here we show that soluble amyloid precursor protein-alpha (sAPP-alpha) decreases A beta generation by directly associating with beta-site APP-converting enzyme (BACE) 1, thereby modulating APP processing. Whereas specifically targeting sAPP-alpha using antibodies enhances A beta production; in transgenic mice with AD-like pathology, sAPP-alpha overexpression decreases beta-amyloid plaques and soluble A beta. In support, immunoneutralization of sAPP-alpha increases APP amyloidogenic processing in these mice. Given our current findings, and because a number of risk factors for sporadic AD serve to lower levels of sAPP-alpha in brains of AD patients, inadequate sAPP-alpha levels may be sufficient to polarize APP processing towards the amyloidogenic, A beta-producing route. Therefore, restoration of sAPP-alpha or enhancement of its association with BACE may be viable strategies to ameliorate imbalances in APP processing that can lead to AD pathogenesis. C1 [Obregon, Demian; Hou, Huayan; Deng, Juan; Giunta, Brian; Tian, Jun; Darlington, Donna; Shahaduzzaman, Md; Zhu, Yuyuan; Tan, Jun] Univ S Florida, Rashid Lab Dev Neurobiol, Silver Child Dev Ctr, Dept Psychiat & Behav Neurosci,Morsani Coll Med, Tampa, FL 33613 USA. [Obregon, Demian; Tan, Jun] James A Haley Vet Hosp, Tampa, FL 33612 USA. [Giunta, Brian] Univ S Florida, Dept Psychiat & Behav Neurosci, Morsani Coll Med, Neuroimmunol Lab, Tampa, FL 33613 USA. [Shahaduzzaman, Md] Univ S Florida, Ctr Aging & Brain Repair, Morsani Coll Med, Dept Neurosurg & Brain Repair, Tampa, FL 33613 USA. [Mori, Takashi] Saitama Med Ctr, Dept Biomed Sci, Kawagoe, Saitama 3508550, Japan. [Mori, Takashi] Saitama Med Ctr, Dept Pathol, Kawagoe, Saitama 3508550, Japan. [Mori, Takashi] Saitama Med Univ, Kawagoe, Saitama 3508550, Japan. [Mattson, Mark P.] NIA, Lab Neurosci, Intramural Res Program, Baltimore, MD 21224 USA. RP Tan, J (reprint author), Univ S Florida, Rashid Lab Dev Neurobiol, Silver Child Dev Ctr, Dept Psychiat & Behav Neurosci,Morsani Coll Med, Tampa, FL 33613 USA. EM jtan@health.usf.edu RI Mattson, Mark/F-6038-2012; Giunta, Brian/H-3817-2011 FU NIH/NIA [R01AG032432, R42AG031586]; National Institute on Aging; Department of Veterans Affairs, Veterans Health Administration, Office of Research and Development, Medical Research Service FX This work was supported by the NIH/NIA [R01AG032432 and R42AG031586 (J.T.)], and the National Institute on Aging Intramural Research Program. This work was also supported in part by the Department of Veterans Affairs, Veterans Health Administration, Office of Research and Development, Medical Research Service through a Veterans Affairs Merit grant (J.T.). We would like to thank Terrence Town and Song Min for helpful discussion. NR 59 TC 42 Z9 43 U1 0 U2 8 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 2041-1723 J9 NAT COMMUN JI Nat. Commun. PD APR PY 2012 VL 3 AR 777 DI 10.1038/ncomms1781 PG 9 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 934PB UT WOS:000303455200014 PM 22491325 ER PT J AU Singh, A Mishra, AK Ylaya, K Hewitt, SM Sharma, KC Saxena, S AF Singh, Avninder Mishra, Ashwani Kumar Ylaya, Kris Hewitt, Stephen M. Sharma, Karam Chand Saxena, Sunita TI Wilms Tumor-1, Claudin-1 and Ezrin Are Useful Immunohistochemical Markers That Help to Distinguish Schwannoma from Fibroblastic Meningioma SO PATHOLOGY & ONCOLOGY RESEARCH LA English DT Article DE Biomarkers; Fibroblastic meningioma; Immunohistochemistry; Schwannoma; Tissue microarray ID EPITHELIAL MEMBRANE ANTIGEN; SOLITARY FIBROUS TUMOR; MENINGEAL HEMANGIOPERICYTOMA; TISSUE MICROARRAY; EXPRESSION; PROGESTERONE; RECEPTORS; DIAGNOSIS; PATHOLOGY; PROTEIN AB The aim of this study is to identify immunohistochemical (IHC) markers that can reliably separate schwannoma (SCHW) and fibroblastic meningioma (FM). We selected 106 cases of intracranial SCHW (n=56) and FM (n=50) and constructed a tissue microarray (TMA) of core diameter of 1.0 mm from archival formalin-fixed paraffin-embedded tissue. ATMA-IHC was performed using 14 antibodies. After IHC staining, 98 cores were found suitable for evaluation. The IHC staining was scored as 0-2+ (0, negative; 1+, weak and/or focal 2+ strong and/or diffuse positive). A discriminant analysis (DA) (Wilks'Lambda test) was performed to assess the relative importance of these biomarkers in classifying the two groups FM and SCHW. It showed that WT-1 (Wilks'lambda 0.085, p<0.001), EMA (Wilks'lambda 0.253, p<0.001), S100 (Wilks'lambda 0.487, p<0.001), Claudin-1 (Wilks' lambda 0.57, p<0.001) and Ezrin (Wilks'lambda 0.656, p<0.001), SPARC (Wilks'lambda 0.751, p<0.01), NP-Y (Wilks'lambda, 0.819, p<0.001) and EGFR (Wilks'lambda 0.845, p=0.026) were some of the statistically significant markers that discriminated SCHW and FM. For sensitivity and specificity for SCHW the significant markers [Area under the curve (95% CI), p-value] by ROC analysis were WT-1 [ 0.990(0.000, 1.000), <0.001], S100 [0.880(0.808, 0.951), <0.001] while for diagnosing FM the most sensitive and specific markers were EMA [0.957(0.914, 1.000), <.001], Claudin-1 [0.857(0.782, 0.932), <0.001] and ezrin [0.792(0.700,0.884),<0.001]. WT-1, Claudin-1 and Ezrin may be potentially useful immunohistochemical adjuncts to EMA and S100 that differentiate SCHW from FM C1 [Singh, Avninder; Mishra, Ashwani Kumar; Saxena, Sunita] Natl Inst Pathol ICMR, New Delhi 110029, India. [Ylaya, Kris; Hewitt, Stephen M.] Natl Canc Inst, Natl Inst Hlth, TARP Lab, Bethesda, MD USA. [Sharma, Karam Chand] Safdarjang Hosp, Dept Neurosurg, New Delhi, India. RP Singh, A (reprint author), Natl Inst Pathol ICMR, Safdarjung Hosp Campus,Room 602,6th floor, New Delhi 110029, India. EM dravninder@yahoo.co.in OI Hewitt, Stephen/0000-0001-8283-1788 FU Indo-US Science and Technology forum, Department of Science and Technology, Government of India FX The authors wish to thank the Indo-US Science and Technology forum, Department of Science and Technology, Government of India for the IUSSTF Research fellowship to Dr Avninder Singh to visit the TARP Lab, NCI, NIH, USA for construction of TMA. The authors also wish to thank Ms Preet Sayal for typing the manuscript and Mr JS Sayal for the adobe photoshop work NR 28 TC 12 Z9 12 U1 0 U2 1 PU SPRINGER PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 1219-4956 J9 PATHOL ONCOL RES JI Pathol. Oncol. Res. PD APR PY 2012 VL 18 IS 2 BP 383 EP 389 DI 10.1007/s12253-011-9456-x PG 7 WC Oncology; Pathology SC Oncology; Pathology GA 935RP UT WOS:000303538200034 PM 21909685 ER PT J AU Bellan, SE Pulliam, JRC Scott, JC Dushoff, J AF Bellan, Steve E. Pulliam, Juliet R. C. Scott, James C. Dushoff, Jonathan CA MMED Organizing Comm TI How to Make Epidemiological Training Infectious SO PLOS BIOLOGY LA English DT Article ID ECO-EPIDEMIOLOGY; BLACK-BOX; DYNAMICS; TRACHOMA; ELIMINATION; DISEASE; MODELS AB Modern infectious disease epidemiology builds on two independently developed fields: classical epidemiology and dynamical epidemiology. Over the past decade, integration of the two fields has increased in research practice, but training options within the fields remain distinct with few opportunities for integration in the classroom. The annual Clinic on the Meaningful Modeling of Epidemiological Data (MMED) at the African Institute for Mathematical Sciences has begun to address this gap. MMED offers participants exposure to a broad range of concepts and techniques from both epidemiological traditions. During MMED 2010 we developed a pedagogical approach that bridges the traditional distinction between classical and dynamical epidemiology and can be used at multiple educational levels, from high school to graduate level courses. The approach is hands-on, consisting of a real-time simulation of a stochastic outbreak in course participants, including realistic data reporting, followed by a variety of mathematical and statistical analyses, stemming from both epidemiological traditions. During the exercise, dynamical epidemiologists developed empirical skills such as study design and learned concepts of bias while classical epidemiologists were trained in systems thinking and began to understand epidemics as dynamic nonlinear processes. We believe this type of integrated educational tool will prove extremely valuable in the training of future infectious disease epidemiologists. We also believe that such interdisciplinary training will be critical for local capacity building in analytical epidemiology as Africa continues to produce new cohorts of well-trained mathematicians, statisticians, and scientists. And because the lessons draw on skills and concepts from many fields in biology-from pathogen biology, evolutionary dynamics of host-pathogen interactions, and the ecology of infectious disease to bioinformatics, computational biology, and statistics-this exercise can be incorporated into a broad array of life sciences courses. C1 [Bellan, Steve E.] Univ Calif Berkeley, Dept Environm Sci Policy & Management, Berkeley, CA 94720 USA. [Pulliam, Juliet R. C.] Natl Inst Hlth, Fogarty Int Ctr, Bethesda, MD USA. [Pulliam, Juliet R. C.] Univ Florida, Dept Biol, Gainesville, FL USA. [Pulliam, Juliet R. C.] Univ Florida, Emerging Pathogens Inst, Gainesville, FL USA. [Scott, James C.] Colby Coll, Dept Math & Stat, Waterville, ME 04901 USA. [Dushoff, Jonathan] McMaster Univ, Dept Biol, Hamilton, ON, Canada. RP Bellan, SE (reprint author), Univ Calif Berkeley, Dept Environm Sci Policy & Management, Berkeley, CA 94720 USA. EM steve.bellan@gmail.com RI Bellan, Steve/D-6368-2013; Pulliam, Juliet/A-6516-2008; OI Bellan, Steve/0000-0002-4110-272X; Pulliam, Juliet/0000-0003-3314-8223; Delva, Wim/0000-0001-8054-1904 FU National Institute of Health [R24TW008822, GM83863]; Henry Wheeler Center for Emerging and Neglected Diseases; African Biomathematics Initiative (National Science Foundation) [DMS-829652]; NSF-NIH Ecology of Infectious Diseases [1134964]; Center for Discrete Mathematics and Theoretical Computer Science; African Institute for Mathematical Sciences; South African Centre for Excellence in Epidemiological Modelling and Analysis; Chang-Lin Tien Environmental Fellowship; Andrew Fellowship; University of California; Mary Thompson Rocca Fellowship; Berkeley Environmental Science, Policy & Management and Entomology Society; National Institute of Health Ecology of Infectious Disease [GM83863]; Research and Policy in Infectious Disease Dynamics (RAPIDD) of the Science and Technology Directorate; Department of Homeland Security; Fogarty International Center, National Institutes of Health FX The Meaningful Modeling of Epidemiological Data Clinics have been generously funded by the National Institute of Health Framework Programs for Global Health Innovations (R24TW008822 to Lee Riley), the Henry Wheeler Center for Emerging and Neglected Diseases, the African Biomathematics Initiative (National Science Foundation grant DMS-829652 awarded to Fred S. Roberts and Avner Friedman), the NSF-NIH Ecology of Infectious Diseases program (NSF award 1134964 to J.R.C.P.), the Center for Discrete Mathematics and Theoretical Computer Science, the African Institute for Mathematical Sciences, and the South African Centre for Excellence in Epidemiological Modelling and Analysis. This work was also partially supported by Chang-Lin Tien Environmental Fellowship, Andrew and Mary Thompson Rocca Fellowships, University of California, Berkeley Environmental Science, Policy & Management and Entomology Society Travel Grants to S. E. B., and National Institute of Health Ecology of Infectious Disease grant (GM83863) to Wayne M. Getz. J.R.C.P is supported by the Research and Policy in Infectious Disease Dynamics (RAPIDD) Program of the Science and Technology Directorate, Department of Homeland Security, and Fogarty International Center, National Institutes of Health. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 29 TC 3 Z9 4 U1 0 U2 7 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA SN 1545-7885 J9 PLOS BIOL JI PLoS. Biol. PD APR PY 2012 VL 10 IS 4 AR e1001295 DI 10.1371/journal.pbio.1001295 PG 8 WC Biochemistry & Molecular Biology; Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics GA 935SV UT WOS:000303541800001 PM 22509129 ER PT J AU Hao, H Kim, DS Klocke, B Johnson, KR Cui, KR Gotoh, N Zang, CZ Gregorski, J Gieser, L Peng, WQ Fann, Y Seifert, M Zhao, KJ Swaroop, A AF Hao, Hong Kim, Douglas S. Klocke, Bernward Johnson, Kory R. Cui, Kairong Gotoh, Norimoto Zang, Chongzhi Gregorski, Janina Gieser, Linn Peng, Weiqun Fann, Yang Seifert, Martin Zhao, Keji Swaroop, Anand TI Transcriptional Regulation of Rod Photoreceptor Homeostasis Revealed by In Vivo NRL Targetome Analysis SO PLOS GENETICS LA English DT Article ID NUCLEAR RECEPTOR NR2E3; S-CONE SYNDROME; GENE-EXPRESSION; LEUCINE-ZIPPER; DIFFERENTIATION FACTOR; RETINAL DEVELOPMENT; PROMOTER ANALYSIS; PRECURSOR CELLS; SUBUNIT GENE; MOUSE RETINA AB A stringent control of homeostasis is critical for functional maintenance and survival of neurons. In the mammalian retina the basic motif leucine zipper transcription factor NRL determines rod versus cone photoreceptor cell fate and activates the expression of many rod-specific genes. Here, we report an integrated analysis of NRL-centered gene regulatory network by coupling chromatin immunoprecipitation followed by high-throughput sequencing (ChIP-Seq) data from Illumina and ABI platforms with global expression profiling and in vivo knockdown studies. We identified approximately 300 direct NRL target genes. Of these, 22 NRL targets are associated with human retinal dystrophies, revealed an enrichment of distinct sets whereas 95 mapped to regions of as yet uncloned retinal disease loci. In analysis of NRL ChIP-Seq peak sequences of transcription factor binding sites. Specifically, we discovered that genes involved in photoreceptor function include binding sites for both NRL and homeodomain protein CRX. Evaluation of 26 ChIP-Seq regions validated their enhancer functions in reporter assays. in vivo knockdown of 16 NRL target genes resulted in death or abnormal morphology of rod photoreceptors, suggesting their importance in maintaining retinal function. We also identified histone demethylase Kdm5b as a novel secondary node in NRL transcriptional hierarchy. Exon array analysis of flow-sorted photoreceptors in which Kdm5b was knocked down by shRNA indicated its role in regulating rod-expressed genes. Our studies identify candidate genes for retinal dystrophies, define cis-regulatory module(s) for photoreceptor-expressed genes and provide a framework for decoding transcriptional regulatory networks that dictate rod homeostasis. C1 [Hao, Hong; Kim, Douglas S.; Gotoh, Norimoto; Gregorski, Janina; Gieser, Linn; Swaroop, Anand] NEI, Neurobiol Neurodegenerat & Repair Lab, NIH, Bethesda, MD 20892 USA. [Klocke, Bernward; Seifert, Martin] Genomatix GmbH, Munich, Germany. [Johnson, Kory R.; Fann, Yang] NINDS, Informat Technol & Bioinformat Program, NIH, Bethesda, MD 20892 USA. [Cui, Kairong; Zhao, Keji] NHLBI, Lab Mol Immunol, NIH, Bethesda, MD 20892 USA. [Zang, Chongzhi; Peng, Weiqun] George Washington Univ, Dept Phys, Washington, DC 20052 USA. RP Hao, H (reprint author), NEI, Neurobiol Neurodegenerat & Repair Lab, NIH, Bethesda, MD 20892 USA. EM swaroopa@nei.nih.gov RI Zang, Chongzhi/D-1445-2011; OI Swaroop, Anand/0000-0002-1975-1141 FU National Eye Institute of the National Institutes of Health; National Institute of Neurological Disorders and Stroke of the National Institutes of Health; National Heart, Lung and Blood Institute of the National Institutes of Health FX This research was supported by intramural programs of the National Eye Institute, National Institute of Neurological Disorders and Stroke, and National Heart, Lung and Blood Institute, of the National Institutes of Health. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 77 TC 43 Z9 44 U1 1 U2 7 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA SN 1553-7404 J9 PLOS GENET JI PLoS Genet. PD APR PY 2012 VL 8 IS 4 BP 380 EP 394 AR e1002649 DI 10.1371/journal.pgen.1002649 PG 15 WC Genetics & Heredity SC Genetics & Heredity GA 934KA UT WOS:000303441800028 PM 22511886 ER PT J AU Kanel, DP Shusterman, M Rong, YK McVey, M AF Kanel, Daniel P. Shusterman, Michael Rong, Yikang McVey, Mitch TI Competition between Replicative and Translesion Polymerases during Homologous Recombination Repair in Drosophila SO PLOS GENETICS LA English DT Article ID DOUBLE-STRAND-BREAK; DNA-POLYMERASES; SACCHAROMYCES-CEREVISIAE; REV1 PROTEIN; IN-VIVO; POL32 SUBUNIT; GAP REPAIR; DELTA; BYPASS; ROLES AB In metazoans, the mechanism by which DNA is synthesized during homologous recombination repair of double-strand breaks is poorly understood. Specifically, the identities of the polymerase(s) that carry out repair synthesis and how they are recruited to repair sites are unclear. Here, we have investigated the roles of several different polymerases during homologous recombination repair in Drosophila melanogaster. Using a gap repair assay, we found that homologous recombination is impaired in Drosophila lacking DNA polymerase zeta and, to a lesser extent, polymerase eta. In addition, the Pol32 protein, part of the polymerase delta complex, is needed for repair requiring extensive synthesis. Loss of Rev1, which interacts with multiple translesion polymerases, results in increased synthesis during gap repair. Together, our findings support a model in which translesion polymerases and the polymerase delta complex compete during homologous recombination repair. In addition, they establish Rev1 as a crucial factor that regulates the extent of repair synthesis. C1 [Kanel, Daniel P.; Shusterman, Michael; McVey, Mitch] Tufts Univ, Dept Biol, Medford, MA 02155 USA. [Rong, Yikang] NCI, Bethesda, MD 20892 USA. [McVey, Mitch] Tufts Sackler Sch Grad Biomed Sci, Genet Program, Boston, MA USA. RP Kanel, DP (reprint author), Tufts Univ, Dept Biol, Medford, MA 02155 USA. EM mitch.mcvey@tufts.edu FU National Science Foundation [MCB-0643253]; National Institutes of Health [R01GM092866]; National Cancer Institute FX This research was supported by grants from the National Science Foundation (MCB-0643253) and the National Institutes of Health (R01GM092866) to MM. Research in the YR lab is supported by the intramural research program of the National Cancer Institute. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 44 TC 23 Z9 23 U1 0 U2 1 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA SN 1553-7404 J9 PLOS GENET JI PLoS Genet. PD APR PY 2012 VL 8 IS 4 BP 447 EP 455 AR e1002659 DI 10.1371/journal.pgen.1002659 PG 9 WC Genetics & Heredity SC Genetics & Heredity GA 934KA UT WOS:000303441800034 PM 22532806 ER PT J AU Kulkarni, M Shakes, DC Guevel, K Smith, HE AF Kulkarni, Madhura Shakes, Diane C. Guevel, Katie Smith, Harold E. TI SPE-44 Implements Sperm Cell Fate SO PLOS GENETICS LA English DT Article ID SEX-DETERMINING GENE; NEMATODE CAENORHABDITIS-ELEGANS; GLUCOCORTICOID MODULATORY ELEMENT; FERTILIZATION-DEFECTIVE MUTANTS; GATA-FACTOR ELT-1; C-ELEGANS; PROTEIN PHOSPHATASE; SAND DOMAIN; MONOCLONAL-ANTIBODIES; TRANSCRIPTION FACTOR AB The sperm/oocyte decision in the hermaphrodite germline of Caenorhabditis elegans provides a powerful model for the characterization of stem cell fate specification and differentiation. The germline sex determination program that governs gamete fate has been well studied, but direct mediators of cell-type-specific transcription are largely unknown. We report the identification of spe-44 as a critical regulator of sperm gene expression. Deletion of spe-44 causes sperm-specific defects cytokinesis, cell cycle progression, and organelle assembly resulting in sterility. Expression of spe-44 correlates precisely with spermatogenesis and is regulated by the germline sex determination pathway. spe-44 is required for the appropriate expression of several hundred sperm-enriched genes. The SPE-44 protein is restricted to the sperm-producing germline where it localizes to the autosomes (which contain sperm genes) but is excluded from the transcriptionally silent. X chromosome (which does not). The orthologous gene in other Caenorhabditis species is similarly expressed in a sex-biased manner, and the protein likewise exhibits autosome-specific localization in developing sperm, strongly suggestive of an evolutionarily conserved role in sperm gene expression. Our analysis represents the first identification of a transcriptional regulator whose primary function is the control of gamete-type-specific transcription in this system. C1 [Shakes, Diane C.; Guevel, Katie] Coll William & Mary, Dept Biol, Williamsburg, VA 23185 USA. [Smith, Harold E.] NIDDK, NIH, Bethesda, MD USA. [Kulkarni, Madhura] Univ Maryland, Dept Cell Biol & Mol Genet, College Pk, MD 20742 USA. RP Kulkarni, M (reprint author), Natl Univ Singapore, Canc Sci Inst Singapore, Singapore 117548, Singapore. EM smithhe2@niddk.nih.gov FU National Science Foundation [0445684]; Jeffress Memorial Trust [J-840]; National Institutes of Health [R15 5GM096309]; Howard Hughes Medical Institute (HHMI) FX This work was supported in part by National Science Foundation grant number 0445684 to HES and grants from the Jeffress Memorial Trust (J-840) and the National Institutes of Health (R15 5GM096309) to DCS. KG received support from the Howard Hughes Medical Institute (HHMI) through the Undergraduate Biological Sciences Education Program to the College of William and Mary. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 81 TC 10 Z9 17 U1 1 U2 11 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA SN 1553-7404 J9 PLOS GENET JI PLoS Genet. PD APR PY 2012 VL 8 IS 4 BP 587 EP 600 AR e1002678 DI 10.1371/journal.pgen.1002678 PG 14 WC Genetics & Heredity SC Genetics & Heredity GA 934KA UT WOS:000303441800044 PM 22570621 ER PT J AU Pastrana, DV Brennan, DC Cuburu, N Storch, GA Viscidi, RP Randhawa, PS Buck, CB AF Pastrana, Diana V. Brennan, Daniel C. Cuburu, Nicolas Storch, Gregory A. Viscidi, Raphael P. Randhawa, Parmjeet S. Buck, Christopher B. TI Neutralization Serotyping of BK Polyomavirus Infection in Kidney Transplant Recipients SO PLOS PATHOGENS LA English DT Article ID VIRUS-LIKE PARTICLES; RENAL-TRANSPLANTATION; INTRAVENOUS IMMUNOGLOBULIN; INTERSTITIAL NEPHRITIS; ALLOGRAFT RECIPIENTS; HEMORRHAGIC CYSTITIS; NEPHROPATHY; IDENTIFICATION; ANTIBODY; VACCINE AB BK polyomavirus (BKV or BKPyV) associated nephropathy affects up to 10% of kidney transplant recipients (KTRs). BKV isolates are categorized into four genotypes. It is currently unclear whether the four genotypes are also serotypes. To address this issue, we developed high-throughput serological assays based on antibody-mediated neutralization of BKV genotype I and IV reporter vectors (pseudoviruses). Neutralization-based testing of sera from mice immunized with BKV-I or BKV-IV virus-like particles (VLPs) or sera from naturally infected human subjects revealed that BKV-I specific serum antibodies are poorly neutralizing against BKV-IV and vice versa. The fact that BKV-I and BKV-IV are distinct serotypes was less evident in traditional VLP-based ELISAs. BKV-I and BKV-IV neutralization assays were used to examine BKV type-specific neutralizing antibody responses in KTRs at various time points after transplantation. At study entry, sera from 5% and 49% of KTRs showed no detectable neutralizing activity for BKV-I or BKV-IV neutralization, respectively. By one year after transplantation, all KTRs were neutralization seropositive for BKV-I, and 43% of the initially BKV-IV seronegative subjects showed evidence of acute seroconversion for BKV-IV neutralization. The results suggest a model in which BKV-IV-specific seroconversion reflects a de novo BKV-IV infection in KTRs who initially lack protective antibody responses capable of neutralizing genotype IV BKVs. If this model is correct, it suggests that pre-vaccinating prospective KTRs with a multivalent VLP-based vaccine against all BKV serotypes, or administration of BKV-neutralizing antibodies, might offer protection against graft loss or dysfunction due to BKV associated nephropathy. C1 [Pastrana, Diana V.; Cuburu, Nicolas; Buck, Christopher B.] NCI, Cellular Oncol Lab, Bethesda, MD 20892 USA. [Brennan, Daniel C.; Storch, Gregory A.] Washington Univ, Sch Med, St Louis, MO USA. [Viscidi, Raphael P.] Johns Hopkins Med Ctr, Dept Pediat, Baltimore, MD USA. [Randhawa, Parmjeet S.] Univ Pittsburgh, Dept Pathol, Med Ctr, Pittsburgh, PA USA. RP Pastrana, DV (reprint author), NCI, Cellular Oncol Lab, Bethesda, MD 20892 USA. EM BuckC@mail.nih.gov OI Buck, Christopher/0000-0003-3165-8094 FU NIH [K24-DK002886, P-30 DK079333, R01-51227, R01-63360]; Center for Cancer Research; NCI FX This work was funded in part by the Intramural Research Program of the NIH, with support from the Center for Cancer Research and the NCI Director's Intramural Innovation Award Program, and in part by NIH grants K24-DK002886 and P-30 DK079333 (DCP) and R01-51227 and R01-63360 (PSR). The funders had no role in study design, data collection and analysis, decision to publish or preparation of the manuscript. NR 62 TC 31 Z9 31 U1 1 U2 2 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA SN 1553-7374 J9 PLOS PATHOG JI PLoS Pathog. PD APR PY 2012 VL 8 IS 4 AR e1002650 DI 10.1371/journal.ppat.1002650 PG 11 WC Microbiology; Parasitology; Virology SC Microbiology; Parasitology; Virology GA 934KY UT WOS:000303444200042 PM 22511874 ER PT J AU Schelhaas, M Shah, B Holzer, M Blattmann, P Kuhling, L Day, PM Schiller, JT Helenius, A AF Schelhaas, Mario Shah, Bhavin Holzer, Michael Blattmann, Peter Kuehling, Lena Day, Patricia M. Schiller, John T. Helenius, Ari TI Entry of Human Papillomavirus Type 16 by Actin-Dependent, Clathrin- and Lipid Raft-Independent Endocytosis SO PLOS PATHOGENS LA English DT Article ID VIRUS-LIKE PARTICLES; SURFACE HEPARAN-SULFATE; SEMLIKI-FOREST-VIRUS; HUMAN KERATINOCYTES; INFECTIOUS ENTRY; CAPSID PROTEIN; HOST-CELLS; CALMODULIN ANTAGONISTS; PHOSPHOLIPASE-C; PATHWAY AB Infectious endocytosis of incoming human papillomavirus type 16 (HPV-16), the main etiological agent of cervical cancer, is poorly characterized in terms of cellular requirements and pathways. Conflicting reports attribute HPV-16 entry to clathrin-dependent and -independent mechanisms. To comprehensively describe the cell biological features of HPV-16 entry into human epithelial cells, we compared HPV-16 pseudovirion (PsV) infection in the context of cell perturbations (drug inhibition, siRNA silencing, overexpression of dominant mutants) to five other viruses (influenza A virus, Semliki Forest virus, simian virus 40, vesicular stomatitis virus, and vaccinia virus) with defined endocytic requirements. Our analysis included infection data, i.e. GFP expression after plasmid delivery by HPV-16 PsV, and endocytosis assays in combination with electron, immunofluorescence, and video microscopy. The results indicated that HPV-16 entry into HeLa and HaCaT cells was clathrin-, caveolin-, cholesterol- and dynamin-independent. The virus made use of a potentially novel ligand-induced endocytic pathway related to macropinocytosis. This pathway was distinct from classical macropinocytosis in regards to vesicle size, cholesterol-sensitivity, and GTPase requirements, but similar in respect to the need for tyrosine kinase signaling, actin dynamics, Na+/H+ exchangers, PAK-1 and PKC. After internalization the virus was transported to late endosomes and/or endolysosomes, and activated through exposure to low pH. C1 [Schelhaas, Mario; Shah, Bhavin; Kuehling, Lena] Univ Munster, Emmy Noether Grp Virus Endocytosis, Inst Mol Virol & Med Biochem, Munster, Germany. [Schelhaas, Mario; Holzer, Michael; Blattmann, Peter; Helenius, Ari] ETH, Inst Biochem, Zurich, Switzerland. [Day, Patricia M.; Schiller, John T.] NCI, Cellular Oncol Lab, NIH, Bethesda, MD 20892 USA. RP Schelhaas, M (reprint author), Univ Munster, Emmy Noether Grp Virus Endocytosis, Inst Mol Virol & Med Biochem, Munster, Germany. EM schelhaas@uni-muenster.de RI Blattmann, Peter/D-2880-2012 OI Blattmann, Peter/0000-0001-9105-6381 FU ETH Zurich; German Science Foundation (DFG) [SCHE 1552/2-1, SFB629A16]; Swiss National Science Foundation (SNF); European Research Council (ERC) FX MS was supported by ETH Zurich (www.ethz.ch) and the German Science Foundation (DFG, www.dfg.de, grants SCHE 1552/2-1, SFB629A16). AH was supported by the ETH Zurich (www.ethz.ch), and by grants from the Swiss National Science Foundation (SNF, www.snf.ch) and the European Research Council (ERC, erc.europa.eu). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 81 TC 99 Z9 101 U1 1 U2 28 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA SN 1553-7374 J9 PLOS PATHOG JI PLoS Pathog. PD APR PY 2012 VL 8 IS 4 AR e1002657 DI 10.1371/journal.ppat.1002657 PG 21 WC Microbiology; Parasitology; Virology SC Microbiology; Parasitology; Virology GA 934KY UT WOS:000303444200046 PM 22536154 ER PT J AU Smith, DL Battle, KE Hay, SI Barker, CM Scott, TW McKenzie, FE AF Smith, David L. Battle, Katherine E. Hay, Simon I. Barker, Christopher M. Scott, Thomas W. McKenzie, F. Ellis TI Ross, Macdonald, and a Theory for the Dynamics and Control of Mosquito-Transmitted Pathogens SO PLOS PATHOGENS LA English DT Review ID A-PRIORI PATHOMETRY; MALARIA TRANSMISSION; VECTORIAL CAPACITY; MATHEMATICAL-MODELS; GENERAL PART; EPIDEMIOLOGY; PROBABILITIES; INTERRUPTION; ERADICATION; ENTOMOLOGY AB Ronald Ross and George Macdonald are credited with developing a mathematical model of mosquito-borne pathogen transmission. A systematic historical review suggests that several mathematicians and scientists contributed to development of the Ross-Macdonald model over a period of 70 years. Ross developed two different mathematical models, Macdonald a third, and various "Ross-Macdonald'' mathematical models exist. Ross-Macdonald models are best defined by a consensus set of assumptions. The mathematical model is just one part of a theory for the dynamics and control of mosquito-transmitted pathogens that also includes epidemiological and entomological concepts and metrics for measuring transmission. All the basic elements of the theory had fallen into place by the end of the Global Malaria Eradication Programme (GMEP, 1955-1969) with the concept of vectorial capacity, methods for measuring key components of transmission by mosquitoes, and a quantitative theory of vector control. The Ross-Macdonald theory has since played a central role in development of research on mosquito-borne pathogen transmission and the development of strategies for mosquito-borne disease prevention. C1 [Smith, David L.] Johns Hopkins Bloomberg Sch Publ Hlth, Dept Epidemiol, Baltimore, MD USA. [Smith, David L.] Johns Hopkins Bloomberg Sch Publ Hlth, Malaria Res Inst, Baltimore, MD USA. [Smith, David L.; Hay, Simon I.; Barker, Christopher M.; Scott, Thomas W.; McKenzie, F. Ellis] NIH, Fogarty Int Ctr, Bethesda, MD 20892 USA. [Battle, Katherine E.; Hay, Simon I.] Univ Oxford, Dept Zool, Spatial Ecol & Epidemiol Grp, Oxford OX1 3PS, England. [Barker, Christopher M.] Univ Calif Davis, Ctr Vectorborne Dis, Davis, CA 95616 USA. [Barker, Christopher M.] Univ Calif Davis, Dept Pathol Microbiol & Immunol, Sch Vet Med, Davis, CA 95616 USA. [Scott, Thomas W.] Univ Calif Davis, Dept Entomol, Davis, CA 95616 USA. RP Smith, DL (reprint author), Johns Hopkins Bloomberg Sch Publ Hlth, Dept Epidemiol, Baltimore, MD USA. EM dlsmith@jhsph.edu RI Smith, David/L-8850-2013; Hay, Simon/F-8967-2015; OI Smith, David/0000-0003-4367-3849; Hay, Simon/0000-0002-0611-7272; Battle, Katherine/0000-0003-2401-2615 FU NIH/NIAID [U19AI089674]; Bill & Melinda Gates Foundation [49446, OPP52250]; US Centers for Disease Control and Prevention [5 U01 EH000418]; Wellcome Trust [079091]; Wellcome Trust, UK FX FEM and DLS began assembling the bibliography at the Fogarty International Center NIH. DLS acknowledges funding from NIH/NIAID (U19AI089674) and the Bill & Melinda Gates Foundation (49446). CMB acknowledges funding from the US Centers for Disease Control and Prevention (5 U01 EH000418). SIH is funded by a Senior Research Fellowship from the Wellcome Trust (079091), which also supported KB. This work forms part of the output of the Malaria Atlas Project (MAP, http://www.map.ox.ac.uk), principally funded by the Wellcome Trust, UK (http://www.wellcome.ac.uk). TWS acknowledges funding from the Bill & Melinda Gates Foundation (OPP52250). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 113 TC 119 Z9 122 U1 4 U2 44 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA SN 1553-7366 EI 1553-7374 J9 PLOS PATHOG JI PLoS Pathog. PD APR PY 2012 VL 8 IS 4 AR e1002588 DI 10.1371/journal.ppat.1002588 PG 13 WC Microbiology; Parasitology; Virology SC Microbiology; Parasitology; Virology GA 934KY UT WOS:000303444200003 PM 22496640 ER PT J AU Vassena, L Miao, HY Cimbro, R Malnati, MS Cassina, G Proschan, MA Hirsch, VM Lafont, BA Morre, M Fauci, AS Lusso, P AF Vassena, Lia Miao, Huiyi Cimbro, Raffaello Malnati, Mauro S. Cassina, Giulia Proschan, Michael A. Hirsch, Vanessa M. Lafont, Bernard A. Morre, Michel Fauci, Anthony S. Lusso, Paolo TI Treatment with IL-7 Prevents the Decline of Circulating CD4(+) T Cells during the Acute Phase of SIV Infection in Rhesus Macaques SO PLOS PATHOGENS LA English DT Article ID SIMIAN IMMUNODEFICIENCY VIRUS; ACTIVE ANTIRETROVIRAL THERAPY; ACUTE HIV-1 INFECTION; GASTROINTESTINAL-TRACT; APOPTOSIS INDUCTION; NONHUMAN-PRIMATES; VIRAL REPLICATION; ANTIVIRAL THERAPY; TYPE-1 INFECTION; LYMPHOID-TISSUE AB Although treatment with interleukin-7 (IL-7) was shown to transiently expand the naive and memory T-cell pools in patients with chronic HIV-1 infection receiving antiretroviral therapy (ART), it is uncertain whether a full immunologic reconstitution can be achieved. Moreover, the effects of IL-7 have never been evaluated during acute HIV-1 (or SIV) infection, a critical phase of the disease in which the most dramatic depletion of CD4(+) T cells is believed to occur. In the present study, recombinant, fully glycosylated simian IL-7 (50 mu g/kg, s.c., once weekly for 7 weeks) was administered to 6 rhesus macaques throughout the acute phase of infection with a pathogenic SIV strain (mac251); 6 animals were infected at the same time and served as untreated controls. Treatment with IL-7 did not cause clinically detectable side effects and, despite the absence of concomitant ART, did not induce significant increases in the levels of SIV replication except at the earliest time point tested (day 4 post-infection). Strikingly, animals treated with IL-7 were protected from the dramatic decline of circulating naive and memory CD4(+) T-cells that occurred in untreated animals. Treatment with IL-7 induced only transient T-cell proliferation, but it was associated with sustained increase in the expression of the anti-apoptotic protein Bcl-2 on both CD4(+) and CD8(+) T cells, persistent expansion of all circulating CD8(+) T-cell subsets, and development of earlier and stronger SIV Tat-specific T-cell responses. However, the beneficial effects of IL-7 were not sustained after treatment interruption. These data demonstrate that IL-7 administration is effective in protecting the CD4(+) T-cell pool during the acute phase of SIV infection in macaques, providing a rationale for the clinical evaluation of this cytokine in patients with acute HIV-1 infection. C1 [Vassena, Lia; Miao, Huiyi; Cimbro, Raffaello; Fauci, Anthony S.; Lusso, Paolo] NIAID, Immunoregulat Lab, NIH, Bethesda, MD 20892 USA. [Vassena, Lia; Malnati, Mauro S.; Cassina, Giulia] DIBIT HSR, Human Virol Unit, Milan, Italy. [Proschan, Michael A.] NIAID, Biostat Res Branch, NIH, Bethesda, MD 20892 USA. [Hirsch, Vanessa M.] NIAID, Mol Med Lab, NIH, Bethesda, MD 20892 USA. [Lafont, Bernard A.] NIAID, Mol Microbiol Lab, NIH, Bethesda, MD 20892 USA. [Morre, Michel] Cytheris, Issy Les Moulineaux, France. RP Vassena, L (reprint author), NIAID, Immunoregulat Lab, NIH, Bldg 10, Bethesda, MD 20892 USA. EM plusso@niaid.nih.gov RI Lafont, Bernard/B-7236-2014; OI Cimbro, Raffaello/0000-0002-6251-5160 FU NIAID; NIH FX This research was supported by the Intramural Research Program of the NIAID, NIH. The funder had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 45 TC 14 Z9 15 U1 0 U2 2 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA SN 1553-7374 J9 PLOS PATHOG JI PLoS Pathog. PD APR PY 2012 VL 8 IS 4 AR e1002636 DI 10.1371/journal.ppat.1002636 PG 11 WC Microbiology; Parasitology; Virology SC Microbiology; Parasitology; Virology GA 934KY UT WOS:000303444200029 PM 22511868 ER PT J AU Klassen, AC Creswell, J Clark, VLP Smith, KC Meissner, HI AF Klassen, Ann C. Creswell, John Clark, Vicki L. Plano Smith, Katherine Clegg Meissner, Helen I. TI Best practices in mixed methods for quality of life research SO QUALITY OF LIFE RESEARCH LA English DT Editorial Material ID METHODS DESIGNS C1 [Klassen, Ann C.] Drexel Univ, Sch Publ Hlth, Philadelphia, PA 19104 USA. [Creswell, John] John Univ Nebraska, Lincoln, NE USA. [Clark, Vicki L. Plano] Univ Nebraska, Lincoln, NE USA. [Smith, Katherine Clegg] Johns Hopkins Bloomberg Sch Publ Hlth, Baltimore, MD USA. [Meissner, Helen I.] NIH, Off Behav & Social Sci Res, Bethesda, MD 20892 USA. RP Klassen, AC (reprint author), Drexel Univ, Sch Publ Hlth, Philadelphia, PA 19104 USA. EM ack57@drexel.edu; creswell@unlserve.unl.edu; vpc@unlserve.unl.edu; kasmith@jhsph.edu; meissneh@mail.nih.gov NR 15 TC 18 Z9 18 U1 2 U2 22 PU SPRINGER PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 0962-9343 J9 QUAL LIFE RES JI Qual. Life Res. PD APR PY 2012 VL 21 IS 3 BP 377 EP 380 DI 10.1007/s11136-012-0122-x PG 4 WC Health Care Sciences & Services; Health Policy & Services; Public, Environmental & Occupational Health SC Health Care Sciences & Services; Public, Environmental & Occupational Health GA 933ZB UT WOS:000303405100002 PM 22311251 ER PT J AU Wallen, GR Baker, K Stolar, M Miller-Davis, C Ames, N Yates, J Bolle, J Pereira, D St Germain, D Handel, D Berger, A AF Wallen, Gwenyth R. Baker, Karen Stolar, Marilyn Miller-Davis, Claiborne Ames, Nancy Yates, Jan Bolle, Jacques Pereira, Donna St Germain, Diane Handel, Daniel Berger, Ann TI Palliative care outcomes in surgical oncology patients with advanced malignancies: a mixed methods approach SO QUALITY OF LIFE RESEARCH LA English DT Article DE Cancer malignancies; Palliative care; Pain management; Symptom management; Mixed methods ID OF-LIFE MEASURES; SOCIAL SUPPORT; PAIN; INTERVENTION; CHALLENGES; NEUROPATHY; CANCER; MODELS; TRIAL; SCALE AB Purpose To prospectively compare outcomes and processes of hospital-based early palliative care with standard care in surgical oncology patients (N = 152). Methods A randomized, mixed methods, longitudinal study evaluated the effectiveness of a hospital-based Pain and Palliative Care Service (PPCS). Interviews were conducted presurgically and at follow-up visits up to 1 year. Primary outcome measures included the Gracely Pain Intensity and Unpleasantness Scales and the Symptom Distress Scale. Qualitative interviews assessed social support, satisfaction with care, and communication with providers. Survival analysis methods explored factors related to treatment crossover and study discontinuation. Models for repeated measures within subjects over time explored treatment and covariate effects on patient-reported pain and symptom distress. Results None of the estimated differences achieved statistical significance; however, for those who remained on study for 12 months, the PPCS group performed better than their standard of care counterparts. Patients identified consistent communication, emotional support, and pain and symptom management as positive contributions delivered by the PPCS. Conclusions It is unclear whether lower pain perceptions despite greater symptom distress were clinically meaningful; however, when coupled with the patients' perceptions of their increased resources and alternatives for pain control, one begins to see the value of an integrated PPCS. C1 [Wallen, Gwenyth R.; Baker, Karen; Handel, Daniel; Berger, Ann] NIH, Pain & Palliat Care Serv, Ctr Clin, Bethesda, MD 20892 USA. [Stolar, Marilyn] United BioSource Corp, Lexington, MA 02420 USA. [Yates, Jan] Shenandoah Univ, Martinsburg, WV 25403 USA. [Bolle, Jacques] NIH, Ctr Clin, Chevy Chase, MD 20815 USA. [Pereira, Donna] George Washington Univ Hosp, Palliat Care Dept, Washington, DC 20037 USA. [St Germain, Diane] NCI, NIH, Bethesda, MD 20892 USA. RP Wallen, GR (reprint author), NIH, Pain & Palliat Care Serv, Ctr Clin, Bldg 10,Room 2B14,10 Ctr Dr, Bethesda, MD 20892 USA. EM gwallen@cc.nih.gov FU Intramural NIH HHS [ZIA CL001136-10] NR 43 TC 10 Z9 10 U1 0 U2 3 PU SPRINGER PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 0962-9343 J9 QUAL LIFE RES JI Qual. Life Res. PD APR PY 2012 VL 21 IS 3 BP 405 EP 415 DI 10.1007/s11136-011-0065-7 PG 11 WC Health Care Sciences & Services; Health Policy & Services; Public, Environmental & Occupational Health SC Health Care Sciences & Services; Public, Environmental & Occupational Health GA 933ZB UT WOS:000303405100005 PM 22101861 ER PT J AU Gershon, RC Lai, JS Bode, R Choi, S Moy, C Bleck, T Miller, D Peterman, A Cella, D AF Gershon, Richard C. Lai, Jin Shei Bode, Rita Choi, Seung Moy, Claudia Bleck, Tom Miller, Deborah Peterman, Amy Cella, David TI Neuro-QOL: quality of life item banks for adults with neurological disorders: item development and calibrations based upon clinical and general population testing SO QUALITY OF LIFE RESEARCH LA English DT Article DE Outcome measures; Quality of life; Neurological disorders; Computerized adaptive testing; item banking ID INFORMATION-SYSTEM PROMIS; OUTCOMES MEASUREMENT; PARALLEL ANALYSIS AB Purpose Neuro-QOL provides a clinically relevant and psychometrically robust health-related quality of life (HRQL) assessment tool for both adults and children with common neurological disorders. We now report the psychometric results for the adult tools. Methods An extensive research, survey and consensus process was used to produce a list of 5 priority adult neurological conditions (stroke, multiple sclerosis, Parkinson's disease, epilepsy and ALS). We identified relevant health related quality of life (HRQL) domains through multiple methods and data sources including a comprehensive review of the literature and literature search, expert interviews and surveys and patient and caregiver focus groups. The final domain framework consisted of 17 domains of Physical, Mental and Social health. There were five phases of item development: (1) identification of 3,482 extant items, (2) item classification and selection, (3) item review and revision, (4) cognitive interviews with 63 patients to assess their understanding of individual items and (5) field testing of 432 representative items. Participants and Procedures Participants were drawn from the US general population and clinical settings, and included both English and Spanish speaking subjects (N = 3,246). Confirmatory factor analysis (CFA) was used to evaluate the dimensionality of unidimensional domains. Where the domain structure was previously unknown, the dataset was split and first analyzed with exploratory factor analysis and then CFA. Samejima's graded response model (GRM) was used to calculate IRT parameters. We further evaluated differential item functioning (DIF) on gender, education and age. Results Thirteen unidimensional calibrated item banks consisting of 297 items were developed. All of the tested item banks had high reliability and few or no locally dependent items. The range of item slopes and thresholds with good information are reported for each of the item banks. The banks can support CAT and the development of short forms. Conclusion The Neuro-QOL measurement system provides item banks and short forms that enable PRO measurement in neurological research, minimizes patient burden and can be used to create multiple instrument types minimizing standard error. The 17 adult measures include 13 calibrated item banks, 3 item pools available for calibration work by others, and 1 stand-alone scale (index). The Neuro-QOL instruments provide a "common metric" of representative concepts for use across patient groups in different studies. C1 [Gershon, Richard C.; Lai, Jin Shei; Bode, Rita; Choi, Seung; Cella, David] Northwestern Univ, Chicago, IL 60611 USA. [Moy, Claudia] Natl Inst Neurol Disorders & Stroke, Bethesda, MD USA. [Bleck, Tom] Rush Univ, Med Ctr, Chicago, IL 60612 USA. [Miller, Deborah] Cleveland Clin, Cleveland, OH 44106 USA. [Peterman, Amy] Univ N Carolina, Charlotte, NC 28223 USA. RP Gershon, RC (reprint author), Northwestern Univ, Chicago, IL 60611 USA. EM gershon@northwestern.edu OI Bleck, Thomas/0000-0002-8267-9787 FU NINDS NIH HHS [N01 NS042360] NR 22 TC 57 Z9 58 U1 4 U2 23 PU SPRINGER PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 0962-9343 J9 QUAL LIFE RES JI Qual. Life Res. PD APR PY 2012 VL 21 IS 3 BP 475 EP 486 DI 10.1007/s11136-011-9958-8 PG 12 WC Health Care Sciences & Services; Health Policy & Services; Public, Environmental & Occupational Health SC Health Care Sciences & Services; Public, Environmental & Occupational Health GA 933ZB UT WOS:000303405100011 PM 21874314 ER PT J AU Gonnord, P Blouin, CM Lamaze, C AF Gonnord, Pauline Blouin, Cedric M. Lamaze, Christophe TI Membrane trafficking and signaling: Two sides of the same coin SO SEMINARS IN CELL & DEVELOPMENTAL BIOLOGY LA English DT Review DE Trafficking; Signaling; Endocytosis; Imaging; Clustering ID T-CELL-ACTIVATION; CLATHRIN-INDEPENDENT ENDOCYTOSIS; SINGLE-MOLECULE TRACKING; PLASMA-MEMBRANE; IMMUNOLOGICAL SYNAPSE; LIVING CELLS; MEDIATED ENDOCYTOSIS; EGF RECEPTOR; DEPENDENT ENDOCYTOSIS; FRET MICROSCOPY AB Recent findings on clathrin-dependent and non clathrin-dependent endocytic routes are currently changing our classical view of endocytosis. Originally seen as a way for the cell to internalize membrane, receptors or various soluble molecules, this process is in fact directly linked to complex signaling pathways. Here, we review new insights in endocytosis and present latest development in imaging techniques that allow us to visualize and follow the dynamics of membrane-associated signaling events at the plasma membrane and other intracellular compartments. The immune synapse is taken as an illustration of the importance of membrane reorganization and proteins clustering to initiate and maintain signaling. Future challenges include understanding the crosslink between traffic and signaling and how all compartmentalized signals are integrated inside the cell at a higher level. (C) 2011 Elsevier Ltd. All rights reserved. C1 [Lamaze, Christophe] Inst Curie, CNRS, Lab Traf Signalisat & Ciblage Intracellulaires, UMR 144,Ctr Rech, F-75248 Paris, France. [Gonnord, Pauline] NIAID, Lab Cellular & Mol Immunol, NIH, Bethesda, MD 20892 USA. [Blouin, Cedric M.; Lamaze, Christophe] CNRS, UMR144, F-75700 Paris, France. RP Lamaze, C (reprint author), Inst Curie, CNRS, Lab Traf Signalisat & Ciblage Intracellulaires, UMR 144,Ctr Rech, F-75248 Paris, France. EM christophe.lamaze@curie.fr OI Blouin, Cedric/0000-0003-0800-0948 NR 119 TC 37 Z9 39 U1 2 U2 32 PU ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD PI LONDON PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND SN 1084-9521 J9 SEMIN CELL DEV BIOL JI Semin. Cell Dev. Biol. PD APR PY 2012 VL 23 IS 2 BP 154 EP 164 DI 10.1016/j.semcdb.2011.11.002 PG 11 WC Cell Biology; Developmental Biology SC Cell Biology; Developmental Biology GA 935UP UT WOS:000303547400004 PM 22085846 ER PT J AU Benninghoff, J van der Ven, A Schloesser, RJ Moessner, R Moller, HJ Rujescu, D AF Benninghoff, Jens van der Ven, Amelie Schloesser, Robert J. Moessner, Rainald Moeller, Hans Juergen Rujescu, Dan TI The complex role of the serotonin transporter in adult neurogenesis and neuroplasticity. A critical review SO WORLD JOURNAL OF BIOLOGICAL PSYCHIATRY LA English DT Review DE Serotonin; serotonin transporter; antidepressants; neuroplasticity; neurogenesis ID NEURAL STEM-CELLS; IN-VIVO MICRODIALYSIS; KNOCK-OUT MICE; EXTRACELLULAR SEROTONIN; MAJOR DEPRESSION; HIPPOCAMPAL NEUROGENESIS; DEFICIENT MICE; BEHAVIORAL-RESPONSES; MONOAMINE-OXIDASE; 5-HT1A RECEPTORS AB Objectives. Studies on the serotonin transporter (SERT) with regard to neurogenesis and neuroplastic effects on the adult brain are scarce. This is intriguing since neurogenesis is believed to play a decisive role in modulating the effect of selective serotonin reuptake inhibitors (SSRI), which are targeting SERT. Methods. Therefore, we reviewed the current scientific literature about the influence of serotonin on neurogenesis with particular emphasis on SERT in various settings, both in vivo and in vitro. Results. Experiments using SERT KO (knock-out) animal models showed that SERT does not directly or indirectly influence neurogenesis in vitro, whereas compensatory mechanism seem to participate in vivo. Conclusion. At least with regard to adult neural stem cells, the impact of serotonin (5-HT) on neuroplasticity and neurogenesis is not due to SERT-mediated effcts. Instead, serotonergic fine-tuning may be exerted by a number of other different mechanisms including endogenous production of 5-HT in adult neural stem cells, uptake of 5-HT into adult neural stem cells by other monoamine transporters, and actions of the 5-HT1A receptors present on these cells. C1 [Benninghoff, Jens; van der Ven, Amelie; Moeller, Hans Juergen; Rujescu, Dan] LMU Univ Munich, Dept Psychiat, D-80336 Munich, Germany. [Schloesser, Robert J.] NIMH, Mol Pathophysiol Lab, Mood & Anxiety Disorders Programme, NIH, Bethesda, MD 20892 USA. [Moessner, Rainald] Univ Bonn, Dept Psychiat, Bonn, Germany. RP Benninghoff, J (reprint author), LMU Univ Munich, Dept Psychiat, D-80336 Munich, Germany. EM jens.benninghoff@med.uni-muenchen.de NR 73 TC 8 Z9 9 U1 2 U2 25 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 PD APR PY 2012 VL 13 IS 4 BP 240 EP 247 PG 8 WC Psychiatry SC Psychiatry GA 933VG UT WOS:000303391400002 PM 22409535 ER PT J AU Canto, AJ Kiefe, CI Goldberg, RJ Rogers, WJ Peterson, ED Wenger, NK Vaccarino, V Frederick, PD Sopko, G Zheng, ZJ Canto, JG AF Canto, Andrew J. Kiefe, Catarina I. Goldberg, Robert J. Rogers, William J. Peterson, Eric D. Wenger, Nanette K. Vaccarino, Viola Frederick, Paul D. Sopko, George Zheng, Zhi-Jie Canto, John G. CA NRMI Investigators TI Differences in symptom presentation and hospital mortality according to type of acute myocardial infarction SO AMERICAN HEART JOURNAL LA English DT Article ID ACUTE CORONARY SYNDROMES; CHEST-PAIN; REGISTRY AB Background Chest pain/discomfort (CP) is the hallmark symptom of acute myocardial infarction (MI), but some patients with MI present without CP. We hypothesized that MI type (ST-segment elevation MI [STEMI] or non-STEMI [NSTEMI]) may be associated with the presence or absence of CP. Methods We investigated the association between CP at presentation and MI type, hospital care, and mortality among 1,143,513 patients with MI in the National Registry of Myocardial Infarction (NRMI) from 1994 to 2006. Results Overall, 43.6% of patients with NSTEMI and 27.1% of patients with STEMI presented without CP. For both MI type, patients without CP were older, were more frequently female, had more diabetes or history of heart failure, were more likely to delay hospital arrival, and were less likely to receive evidence-based medical therapies and invasive cardiac procedures. Multivariable analysis indicated that NSTEMI (vs STEMI) was the strongest predictor of atypical symptoms (adjusted odds ratio [95% CI], 1.93 [1.91-1.95]). Within the 4 CP/MI type categories, hospital mortality was highest for no CP/STEMI (27.8%), followed by no CP/NSTEMI (15.3%) and CP/STEMI (9.6%), and was lowest for CP/NSTEMI (5.4%). The adjusted odds ratio of mortality was 1.38 (1.35-1.41) for no CP (vs CP) in the STEMI group and 1.31 (1.28-1.34) in the NSTEMI group. Conclusions Hospitalized patients with NSTEMI were nearly 2-fold more likely to present without CP than patients with STEMI. Patients with MI without CP were less quickly diagnosed and treated and had higher adjusted odds of hospital mortality, regardless of whether they had ST-segment elevation. (Am Heart J 2012; 163:572-9.) C1 [Canto, John G.] Watson Clin, Lakeland, FL 33805 USA. [Canto, John G.] Lakeland Reg Med Ctr, Lakeland, FL USA. [Canto, Andrew J.] Int Baccalaureate Sch, Bartow, FL USA. [Kiefe, Catarina I.; Goldberg, Robert J.] Univ Massachusetts, Sch Med, Dept Quantitat Hlth Sci, Worcester, MA USA. [Rogers, William J.] Univ Alabama, Med Ctr, Birmingham, AL 35294 USA. [Peterson, Eric D.] Duke Univ, Med Ctr, Duke Clin Res Inst, Durham, NC USA. [Wenger, Nanette K.; Vaccarino, Viola] Emory Sch Med, Dept Med, Div Cardiol, San Francisco, CA USA. [Vaccarino, Viola] Emory Univ, Dept Epidemiol, Rollins Sch Publ Hlth, San Francisco, CA USA. [Frederick, Paul D.] ICON Late Phase & Outcomes Res, San Francisco, CA USA. [Sopko, George] NHLBI, Bethesda, MD 20892 USA. [Zheng, Zhi-Jie] Shanghai Jiao Tong Univ, Sch Publ Hlth, Shanghai 200030, Peoples R China. RP Canto, JG (reprint author), Watson Clin, 1600 Lakeland Hill Blvd, Lakeland, FL 33805 USA. EM jcanto@watsonclinic.com OI Frederick, Paul/0000-0002-7936-5488 FU pharmaceutical industry; Genentech, Inc FX Paul D. Frederick is an employee of ICON, a contract research organization that receives research funding from the pharmaceutical industry. He was paid by Genentech, Inc, to provide biostatistical and analytic services. George Sopko is an employee of the Health and Human Services, National Institutes of Health, and National Heart, Lung, and Blood Institute, and the material presented should not be taken as representing the viewpoint of these organizations. NR 9 TC 19 Z9 20 U1 0 U2 7 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0002-8703 J9 AM HEART J JI Am. Heart J. PD APR PY 2012 VL 163 IS 4 BP 572 EP 579 DI 10.1016/j.ahj.2012.01.020 PG 8 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 930AD UT WOS:000303106800017 PM 22520522 ER PT J AU Magnani, JW Moser, CB Murabito, JM Nelson, KP Fontes, JD Lubitz, SA Sullivan, LM Ellinor, PT Benjamin, EJ AF Magnani, Jared W. Moser, Carlee B. Murabito, Joanne M. Nelson, Kerrie P. Fontes, Joao D. Lubitz, Steven A. Sullivan, Lisa M. Ellinor, Patrick T. Benjamin, Emelia J. TI Age of natural menopause and atrial fibrillation: The Framingham Heart Study SO AMERICAN HEART JOURNAL LA English DT Article ID C-REACTIVE PROTEIN; CARDIOVASCULAR RISK-FACTORS; POSTMENOPAUSAL WOMEN; CARDIAC ELECTROPHYSIOLOGY; GENDER-DIFFERENCES; ESTROGEN-RECEPTOR; DISEASE RISK; MORTALITY; FAILURE; HYPERTENSION AB Background Early menopausal age is associated with risk of cardiovascular events including myocardial infraction, stroke, and increased mortality. Relations between menopausal age and atrial fibrillation (AF) have not been investigated. We examined the association between menopausal age and AF. Methods Framingham Heart Study women >= 60 years old without prevalent AF and natural menopause were followed up for 10 years or until incident AF. Menopausal age was modeled as a continuous variable and by categories (<45, 45-53, and >53 years). We used Cox proportional hazards regression to determine associations between menopausal age and AF risk. Results In 1,809 Framingham women (2,662 person-examinations, mean baseline age 71.4 +/- 7.6 years, menopausal age 49.8 +/- 3.6 years), there were 273 unique participants with incident AF. We did not identify a significant association between the SD of menopausal age (3.6 years) and AF (hazard ratio [HR] per SD 0.94, 95% CI 0.83-1.06; P = .29). In a multivariable model with established risk factors for AF, menopausal age was not associated with incident AF (HR per SD 0.97, 95% CI 0.86-1.09; P = .60). Examining categorical menopausal age, earlier menopausal age (<45 years) was not significantly associated with increased AF risk compared with older menopausal age >53 years (HR 1.20, 95% CI 0.74-1.94; P = .52) or menopausal age 45 to 53 years (HR 1.38, 95% CI 0.93-2.04; P = .11). Conclusion In our moderate-sized, community-based sample, we did not identify menopausal age as significantly increasing AF risk. However, future larger studies will need to examine whether there is a small effect of menopausal age on AF risk. (Am Heart J 2012;163:729-34.) C1 [Magnani, Jared W.] Boston Univ, Sch Med, Sect Cardiovasc Med, Dept Med, Boston, MA 02118 USA. [Magnani, Jared W.; Murabito, Joanne M.; Fontes, Joao D.; Benjamin, Emelia J.] NHLBI, Framingham Heart Study, Framingham, MA USA. [Magnani, Jared W.; Murabito, Joanne M.; Fontes, Joao D.; Benjamin, Emelia J.] Boston Univ, Framingham Heart Study, Framingham, MA USA. [Moser, Carlee B.; Nelson, Kerrie P.; Sullivan, Lisa M.] Boston Univ, Sch Publ Hlth, Dept Biostat, Boston, MA USA. [Murabito, Joanne M.] Boston Univ, Gen Internal Med Sect, Dept Med, Boston, MA 02215 USA. [Lubitz, Steven A.; Ellinor, Patrick T.] Massachusetts Gen Hosp, Cardiovasc Res Ctr, Charlestown, MA USA. [Lubitz, Steven A.; Ellinor, Patrick T.] Massachusetts Gen Hosp, Cardiac Arrhythmia Serv, Boston, MA 02114 USA. [Benjamin, Emelia J.] Boston Univ, Sch Med, Dept Med, Prevent Med Sect, Boston, MA 02118 USA. [Benjamin, Emelia J.] Boston Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA USA. RP Magnani, JW (reprint author), Boston Univ, Sch Med, Sect Cardiovasc Med, Dept Med, 88 E Newton St, Boston, MA 02118 USA. EM jmagnani@bu.edu OI Murabito, Joanne/0000-0002-0192-7516; Sullivan, Lisa/0000-0003-0726-7149; Benjamin, Emelia/0000-0003-4076-2336 FU American Heart Association [09FTF219028]; NIH [HL092577, RO1AG028321, RC1-HL01056, 1R01HL102214, 5R21DA027021, 1RO1HL104156, 1K24HL105780, 6R01-NS17950, N01-HC25195]; Evans Center for Interdisciplinary Biomedical Research ARC FX Dr. Magnani is supported by American Heart Association Award 09FTF219028. This work was supported by grants from the NIH to Drs. Benjamin and Ellinor (HL092577), Dr. Benjamin (RO1AG028321, RC1-HL01056, 1R01HL102214) and Dr. Ellinor (5R21DA027021, 1RO1HL104156, 1K24HL105780) and 6R01-NS17950, N01-HC25195. This work was partially supported by the Evans Center for Interdisciplinary Biomedical Research ARC on "Atrial Fibrillation at Boston University (http://www.bumc.bu.edu/evanscenteribr/). NR 47 TC 4 Z9 4 U1 1 U2 7 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0002-8703 J9 AM HEART J JI Am. Heart J. PD APR PY 2012 VL 163 IS 4 BP 729 EP 734 DI 10.1016/j.ahj.2012.01.010 PG 6 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 930AD UT WOS:000303106800036 PM 22520541 ER PT J AU Cashion, AK Zeimetz, M AF Cashion, Ann K. Zeimetz, Marie TI IOM's Clarion Call for Health Care Transformation: The Role of Nursing Science SO BIOLOGICAL RESEARCH FOR NURSING LA English DT Editorial Material C1 [Cashion, Ann K.] Univ Tennessee, Ctr Hlth Sci, Coll Nursing, Memphis, TN 38163 USA. [Zeimetz, Marie] NINR, NIH, Bethesda, MD 20892 USA. RP Cashion, AK (reprint author), Univ Tennessee, Ctr Hlth Sci, Coll Nursing, 920 Madison,Suite 507, Memphis, TN 38163 USA. EM acashion@uthsc.edu NR 6 TC 1 Z9 1 U1 0 U2 1 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 1099-8004 J9 BIOL RES NURS JI Biol. Res. Nurs. PD APR PY 2012 VL 14 IS 2 BP 113 EP 114 DI 10.1177/1099800412439746 PG 2 WC Nursing SC Nursing GA 930HL UT WOS:000303128200001 PM 22529184 ER PT J AU Insel, KC Merkle, CJ Hsiao, CP Vidrine, AN Montgomery, DW AF Insel, Kathleen C. Merkle, Carrie J. Hsiao, Chao-Pin Vidrine, Amy N. Montgomery, David W. TI Biomarkers for Cognitive Aging Part I: Telomere Length, Blood Pressure and Cognition Among Individuals with Hypertension SO BIOLOGICAL RESEARCH FOR NURSING LA English DT Article DE telomere length; biological age; RT-qPCR; cognitive processes; blood pressure; hypertension ID OLDER; AGE; MORTALITY; WOMEN; ATHEROSCLEROSIS; ASSOCIATION; DEMENTIA; DECLINE; DISEASE; STRESS AB Chronological age is used as a marker for age-associated changes in cognitive function. However, there is great interindividual variability in cognitive ability among people of the same age. Physiological age rather than chronological age should be more closely associated with age-related cognitive changes because these changes are not universal and are likely dependent on several factors in addition to the number of years lived. Cognitive function is associated with successful self-management, and a biological marker that reflects physiological age and is associated with cognitive function could be used to identify risk for failure to self-manage. The purpose of this study was to investigate the association between telomere length, a known biomarker of age; blood pressure; cognitive assessments; and adherence to antihypertensive medication among community-dwelling middle-aged and older adults. The authors administered a battery of cognitive assessments to 42 participants (M = 69 years of age), collected blood samples, and isolated peripheral blood mononuclear leukocytes for genomic DNA. The authors determined relative telomere length using Cawthon's method for real-time quantitative polymerase chain reaction (RT-qPCR) and measured medication adherence using an electronic medication monitoring system (MEMS by Aardex) over 8 weeks. Findings indicate that telomere length was inversely associated with systolic blood pressure (r = -.38, p < .01) and diastolic blood pressure (r = -.42, p < .01) but not with cognitive assessments or adherence. The authors discuss the nonsignificant findings between telomere length and cognitive assessments including the potential modifying role of gender. C1 [Insel, Kathleen C.; Merkle, Carrie J.; Vidrine, Amy N.; Montgomery, David W.] Univ Arizona, Coll Nursing, Tucson, AZ 85721 USA. [Hsiao, Chao-Pin] NINR, Symptom Management Branch, Intramural Res Program, NIH, Bethesda, MD 20892 USA. RP Insel, KC (reprint author), Univ Arizona, Coll Nursing, POB 210203, Tucson, AZ 85721 USA. EM insel@email.arizona.edu FU National Institutes of Health [R03 NR010010-01, P20 NR007794] FX The authors disclosed receipt of the following financial support for the research and/or authorship of this article: This research was supported by the National Institutes of Health, R03 NR010010-01 and P20 NR007794. NR 52 TC 8 Z9 8 U1 0 U2 6 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 1099-8004 J9 BIOL RES NURS JI Biol. Res. Nurs. PD APR PY 2012 VL 14 IS 2 BP 124 EP 132 DI 10.1177/1099800411406433 PG 9 WC Nursing SC Nursing GA 930HL UT WOS:000303128200003 PM 21586494 ER PT J AU Feng, LZ Shay, DK Jiang, Y Zhou, H Chen, X Zheng, YD Jiang, LL Zhang, QJ Lin, H Wang, SJ Ying, YY Xu, YJ Wang, ND Feng, ZJ Viboud, C Yang, WZ Yu, HJ AF Feng, Luzhao Shay, David K. Jiang, Yong Zhou, Hong Chen, Xin Zheng, Yingdong Jiang, Lili Zhang, Qingjun Lin, Hong Wang, Shaojie Ying, Yanyan Xu, Yanjun Wang, Nanda Feng, Zijian Viboud, Cecile Yang, Weizhong Yu, Hongjie TI Influenza-associated mortality in temperate and subtropical Chinese cities, 2003-2008 SO BULLETIN OF THE WORLD HEALTH ORGANIZATION LA English DT Article ID OF-DEATH STATISTICS; SEASONAL INFLUENZA; EXCESS MORTALITY; UNITED-STATES; TROPICAL SINGAPORE; PNEUMONIA; EPIDEMIC; IMPACT; HOSPITALIZATION; VACCINATION AB Objective To estimate influenza-associated mortality in urban China. Methods Influenza-associated excess mortality for the period 2003-2008 was estimated in three cities in temperate northern China and five cities in the subtropical south of the country. The estimates were derived from models based on negative binomial regressions, vital statistics and the results of weekly influenza virus surveillance. Findings Annual influenza-associated excess mortality, for all causes, was 18.0 (range: 10.9-32.7) deaths per 100 000 population in the northern cities and 11.3 (range: 7.3-1.7.8) deaths per 100000 in the southern cities. Excess mortality for, respiratory and circulatory disease was 12.4 (range: 7.4-22.2) and 8.8 (range: 5.5-13.6) deaths per 100 000 people in the northern and southern cities, respectively. Most (86%) deaths occurred among people aged 65 years. Influenza-associated excess mortality was higher in B-virus-dominant seasons than in seasons when A(H3N2) or A(H1N1) predominated, and more than half of all influenza-associated mortality was associated with influenza B virus. Conclusion Between 2003 and 2008, seasonal influenza, particularly that caused by the influenza B virus, was associated with substantial mortality in three cities in the temperate north of China and five cities in the subtropical south of the country: C1 [Jiang, Yong; Yu, Hongjie] Chinese Ctr Dis Control & Prevent, Natl Ctr Chron & Noncommunicable Dis Control & Pr, Beijing 102206, Peoples R China. [Shay, David K.; Zhou, Hong] Ctr Dis Control & Prevent, Natl Ctr Immunizat & Resp Dis, Atlanta, GA USA. [Zheng, Yingdong] Peking Univ, Sch Publ Hlth, Beijing 100871, Peoples R China. [Jiang, Lili] Shanghai Municipal Ctr Dis Control & Prevent, Shanghai, Peoples R China. [Zhang, Qingjun] Hubei Prov Ctr Dis Control & Prevent, Wuhan, Peoples R China. [Lin, Hong] Dalian Ctr Dis Control & Prevent, Dalian, Peoples R China. [Wang, Shaojie] Qingdao Ctr Dis Control & Prevent, Qingdao, Peoples R China. [Ying, Yanyan] Ningbo Ctr Dis Control & Prevent, Ningbo, Zhejiang, Peoples R China. [Xu, Yanjun] Guangdong Prov Ctr Dis Control & Prevent, Guangzhou, Guangdong, Peoples R China. [Wang, Nanda] Zhaoyuan Ctr Dis Control & Prevent, Yantai, Peoples R China. [Viboud, Cecile] NIH, Fogarty Int Ctr, Bethesda, MD 20892 USA. RP Yu, HJ (reprint author), Chinese Ctr Dis Control & Prevent, Natl Ctr Chron & Noncommunicable Dis Control & Pr, 155 Changbai Rd, Beijing 102206, Peoples R China. EM yuhj@chinacdc.cn FU China-US Collaborative Program on Emerging and Re-emerging Infectious Diseases FX This study was supported by the China-US Collaborative Program on Emerging and Re-emerging Infectious Diseases. NR 34 TC 41 Z9 50 U1 1 U2 8 PU WORLD HEALTH ORGANIZATION PI GENEVA 27 PA MARKETING AND DISSEMINATION, CH-1211 GENEVA 27, SWITZERLAND SN 0042-9686 J9 B WORLD HEALTH ORGAN JI Bull. World Health Organ. PD APR PY 2012 VL 90 IS 4 BP 279 EP 288 DI 10.2471/BLT.11.096958 PG 10 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 932EL UT WOS:000303273100018 PM 22511824 ER PT J AU Gudmundsson, LS Scher, AI AF Gudmundsson, Larus S. Scher, Ann I. TI High migraine prevalence in Parma: Why? SO CEPHALALGIA LA English DT Editorial Material ID SOCIOECONOMIC-STATUS; UNITED-STATES; HEADACHE; POPULATION; CLASSIFICATION; RISK; AURA; MORTALITY; CRITERIA; BURDEN C1 [Gudmundsson, Larus S.; Scher, Ann I.] Uniformed Serv Univ Hlth Sci, Dept Prevent Med & Biometr, Bethesda, MD 20814 USA. [Gudmundsson, Larus S.; Scher, Ann I.] NIA, Lab Epidemiol Demog & Biometry, NIH, Bethesda, MD 20892 USA. RP Gudmundsson, LS (reprint author), Uniformed Serv Univ Hlth Sci, Dept Prevent Med & Biometr, 4301 Jones Bridge Rd, Bethesda, MD 20814 USA. EM larus.gudmundsson@usuhs.edu NR 34 TC 2 Z9 2 U1 0 U2 1 PU SAGE PUBLICATIONS LTD PI LONDON PA 1 OLIVERS YARD, 55 CITY ROAD, LONDON EC1Y 1SP, ENGLAND SN 0333-1024 J9 CEPHALALGIA JI Cephalalgia PD APR PY 2012 VL 32 IS 5 BP 355 EP 357 DI 10.1177/0333102412439799 PG 3 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 929LQ UT WOS:000303065700001 PM 22436372 ER PT J AU Klotz, L Chetner, M Chin, J Finelli, T Fleshner, N Fradet, Y Goldenberg, L Nickel, JC Siemens, R So, A Sugar, L Zlotta, A Klein, E Parnes, H Penson, D AF Klotz, Laurence Chetner, Michael Chin, Joseph Finelli, Tony Fleshner, Neil Fradet, Yves Goldenberg, Larry Nickel, J. Curtis Siemens, Robert So, Alan Sugar, Linda Zlotta, Alexandre Klein, Eric Parnes, Howard Penson, David TI Canadian Consensus Conference: The FDA decision on the use of 5ARIs SO CUAJ-CANADIAN UROLOGICAL ASSOCIATION JOURNAL LA English DT Article ID PROSTATE-CANCER PREVENTION; TRIAL; DUTASTERIDE; ANTIGEN; MEN C1 [Klotz, Laurence; Zlotta, Alexandre] Univ Toronto, Sunnybrook Hlth Sci Ctr, Dept Urol, Toronto, ON M4N 3M5, Canada. [Chetner, Michael] Univ Alberta Hosp, Div Urol, Edmonton, AB T6G 2B7, Canada. [Chin, Joseph] Western Univ, Div Urol Surg, London, ON, Canada. [Finelli, Tony] Princess Margaret Hosp, Div Urol Minimally Invas Surg, Dept Surg Oncol, Toronto, ON M4X 1K9, Canada. [Fleshner, Neil] Univ Hlth Network, Div Urol, Toronto, ON, Canada. [Fradet, Yves] Univ Laval, Dept Urol, Quebec City, PQ, Canada. [Goldenberg, Larry; So, Alan] Univ British Columbia, Dept Urol Sci, Vancouver, BC, Canada. [Nickel, J. Curtis; Siemens, Robert] Queens Univ, Dept Urol, Kingston, ON, Canada. [Sugar, Linda] Sunnybrook Hlth Sci Ctr, Dept Pathol, Toronto, ON M4N 3M5, Canada. [Klein, Eric] Glickman Urol & Kidney Inst, Cleveland, OH USA. [Parnes, Howard] NCI, Prostate & Urol Canc Res Grp, Canc Prevent Div, Bethesda, MD 20892 USA. [Penson, David] Vanderbilt Univ, Med Ctr, Div Urol, Nashville, TN USA. RP Klotz, L (reprint author), Univ Toronto, Sunnybrook Hlth Sci Ctr, Dept Urol, 2075 Bayview Ave,Room MG 204, Toronto, ON M4N 3M5, Canada. EM laurence.klotz@sunnybrook.ca RI Zlotta, Alexandre/K-8285-2015 NR 11 TC 3 Z9 3 U1 0 U2 1 PU CANADIAN UROLOGICAL ASSOCIATION PI DORVAL PA 185 DORVAL AVENUE, STE 401, DORVAL, QC H9S 5J9, CANADA SN 1911-6470 J9 CUAJ-CAN UROL ASSOC JI CUAJ-Can. Urol. Assoc. J. PD APR PY 2012 VL 6 IS 2 BP 83 EP 88 DI 10.5489/cuaj.12058 PG 6 WC Urology & Nephrology SC Urology & Nephrology GA 932LE UT WOS:000303291800003 PM 22511412 ER PT J AU Xiong, YM Bosselut, R AF Xiong, Yumei Bosselut, Remy TI CD4-CD8 differentiation in the thymus: connecting circuits and building memories SO CURRENT OPINION IN IMMUNOLOGY LA English DT Review ID T-CELL LINEAGE; DOUBLE-POSITIVE THYMOCYTES; HELPER TYPE-1 CELLS; TRANSCRIPTION FACTORS; GENE-EXPRESSION; CD4 EXPRESSION; CYTOTOXIC-LINEAGE; RUNX PROTEINS; NKT CELLS; THPOK AB The proper choice of the CD4-helper or CD8-cytotoxic lineages by developing T cells is crucial for the generation of an antigen-responsive and functionally fit T cell repertoire. Here we present a brief overview of the transcr ptional control of this process, with emphasis on two issues. The study of Cd4 expression, that had previously generated important paradigms for transcriptional regulation in eukaryotic cells, now brings new twists to the concept of 'epigenetic memory'. And connections are emerging between transcriptional regulators critical for commitment to either lineage. The present review attempts to integrate these findings and d scusses the still elusive mechanisms that match CD4-CD8 lineage differentiation to MHC specificity. C1 [Xiong, Yumei; Bosselut, Remy] NCI, Lab Immune Cell Biol, Ctr Canc Res, NIH, Bethesda, MD 20892 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 National Cancer Institute, Center for Cancer Research FX We thank A. Gegonne, P. Love and M. Vacchio for reading the manuscript and apologize to colleagues whose work could not be discussed because of space limitations. Research work in the authors' laboratory is supported by the Intramural Research Program or the National Cancer Institute, Center for Cancer Research. NR 61 TC 17 Z9 18 U1 1 U2 6 PU CURRENT BIOLOGY LTD PI LONDON PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND SN 0952-7915 J9 CURR OPIN IMMUNOL JI Curr. Opin. Immunol. PD APR PY 2012 VL 24 IS 2 BP 139 EP 145 DI 10.1016/j.coi.2012.02.002 PG 7 WC Immunology SC Immunology GA 931AY UT WOS:000303187600003 PM 22387323 ER PT J AU Aggarwal, M Brosh, RM AF Aggarwal, Monika Brosh, Robert M., Jr. TI Functional analyses of human DNA repair proteins important for aging and genomic stability using yeast genetics SO DNA REPAIR LA English DT Review DE Aging; DNA repair; Yeast; Genetics; Genomic stability ID BASE EXCISION-REPAIR; NONPOLYPOSIS COLORECTAL-CANCER; HEMATOPOIETIC STEM-CELLS; CHRONOLOGICAL LIFE-SPAN; WERNER-SYNDROME PROTEIN; SACCHAROMYCES-CEREVISIAE; MISMATCH REPAIR; FLAP ENDONUCLEASE-1; RECQ HELICASES; P53 MUTANTS AB Model systems have been extremely useful for studying various theories of aging. Studies of yeast have been particularly helpful to explore the molecular mechanisms and pathways that affect aging at the cellular level in the simple eukaryote. Although genetic analysis has been useful to interrogate the aging process, there has been both interest and debate over how functionally conserved the mechanisms of aging are between yeast and higher eukaryotes, especially mammalian cells. One area of interest has been the importance of genomic stability for age-related processes, and the potential conservation of proteins and pathways between yeast and human. Translational genetics have been employed to examine the functional roles of mammalian proteins using yeast as a pliable model system. In the current review recent advancements made in this area are discussed, highlighting work which shows that the cellular functions of human proteins in DNA repair and maintenance of genomic stability can be elucidated by genetic rescue experiments performed in yeast. Published by Elsevier B.V. C1 [Aggarwal, Monika; Brosh, Robert M., Jr.] NIA, Lab Mol Gerontol, NIH, NIH Biomed Res Ctr, Baltimore, MD 21224 USA. RP Brosh, RM (reprint author), NIA, Lab Mol Gerontol, NIH, NIH Biomed Res Ctr, 251 Bayview Blvd, Baltimore, MD 21224 USA. EM broshr@mail.nih.gov FU NIH, National Institute on Aging FX This work was supported by the Intramural Research program of the NIH, National Institute on Aging. We wish to thank Dr. Avvaru Suhasini and Dr. Jian Lu, Laboratory of Molecular Gerontology, NIA-NIH for critical reading of the manuscript. NR 163 TC 3 Z9 3 U1 2 U2 9 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 1568-7864 J9 DNA REPAIR JI DNA Repair PD APR 1 PY 2012 VL 11 IS 4 BP 335 EP 348 DI 10.1016/j.dnarep.2012.01.013 PG 14 WC Genetics & Heredity; Toxicology SC Genetics & Heredity; Toxicology GA 929XS UT WOS:000303099600002 PM 22349084 ER PT J AU Hanssen-Bauer, A Solvang-Garten, K Gilljam, KM Torseth, K Wilson, DM Akbari, M Otterlei, M AF Hanssen-Bauer, Audun Solvang-Garten, Karin Gilljam, Karin Margaretha Torseth, Kathrin Wilson, David M., III Akbari, Mansour Otterlei, Marit TI The region of XRCC1 which harbours the three most common nonsynonymous polymorphic variants, is essential for the scaffolding function of XRCC1 SO DNA REPAIR LA English DT Article DE XRCC1 Arg194Trp; XRCC1 Arg280His; XRCC1 Arg399GIn; DNA repair complexes; Micro-irradiation ID STRAND-BREAK REPAIR; DNA-LIGASE-III; BASE EXCISION-REPAIR; SISTER-CHROMATID EXCHANGE; POLYMERASE-BETA; CANCER RISK; POLY(ADP-RIBOSE) POLYMERASE; PROTEIN; DAMAGE; REPLICATION AB XRCC1 functions as a non-enzymatic, scaffold protein in single strand break repair (SSBR) and base excision repair (BER). Here, we examine different regions of XRCC1 for their contribution to the scaffolding functions of the protein. We found that the central BRCT1 domain is essential for recruitment of XRCC1 to sites of DNA damage and DNA replication. Also, we found that ectopic expression of the region from residue 166-436 partially rescued the methyl methanesulfonate (MMS) hypersensitivity of XRCC1-deficient EM9 cells, suggesting a key role for this region in mediating DNA repair. The three most common amino acid variants of XRCC1, Argl 94Trp, Arg280His and Arg399G1n, are located within the region comprising the NLS and BRCT1 domains, and these variants may be associated with increased incidence of specific types of cancer. While we could not detect differences in the intra-nuclear localization or the ability to support recruitment of POL beta or PNKP to micro-irradiated sites for these variants relative to the conservative protein, we did observe lower foci intensity after micro-irradiation and a reduced stability of the foci with the Arg280His and Arg399GIn variants, respectively. Furthermore, when challenged with MMS or hydrogen peroxide, we detected small but consistent differences in the repair profiles of cells expressing these two variants in comparison to the conservative protein. (C) 2012 Elsevier B.V. All rights reserved. C1 [Hanssen-Bauer, Audun; Solvang-Garten, Karin; Gilljam, Karin Margaretha; Torseth, Kathrin; Akbari, Mansour; Otterlei, Marit] Norwegian Univ Sci & Technol, Dept Canc Res & Mol Med, Fac Med, N-7006 Trondheim, Norway. [Wilson, David M., III] NIA, Lab Mol Gerontol, NIH, Baltimore, MD 21224 USA. RP Otterlei, M (reprint author), Norwegian Univ Sci & Technol, Dept Canc Res & Mol Med, Fac Med, NO-7489 Trondheim, Norway. EM marit.otterlei@ntnu.no OI Akbari, Mansour/0000-0002-6490-7766 FU St. Olavs Hospital, Trondheim, Norway; Liaison Committee; Norwegian Research Council; Norwegian Cancer Society; NIH, National Institute on Aging, USA FX We would like to thank Nina-Beate Liabakk for technical assistance. This work is supported by The Cancer Fund at St. Olavs Hospital, Trondheim, Norway, The Liaison Committee between the Central Norway Regional Health Authority (RHA) and the Norwegian University of Science and Technology (NTNU), Norway, The Norwegian Research Council program FUGE, The Norwegian Cancer Society, and the Intramural Research Program of the NIH, National Institute on Aging, USA. NR 50 TC 13 Z9 13 U1 0 U2 5 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 1568-7864 J9 DNA REPAIR JI DNA Repair PD APR 1 PY 2012 VL 11 IS 4 BP 357 EP 366 DI 10.1016/j.dnarep.2012.01.001 PG 10 WC Genetics & Heredity; Toxicology SC Genetics & Heredity; Toxicology GA 929XS UT WOS:000303099600004 PM 22281126 ER PT J AU Karata, K Vaisman, A Goodman, MF Woodgate, R AF Karata, Kiyonobu Vaisman, Alexandra Goodman, Myron F. Woodgate, Roger TI Simple and efficient purification of Escherichia coli DNA polymerase V: Cofactor requirements for optimal activity and processivity in vitro SO DNA REPAIR LA English DT Article DE UmuC; UmuD '; SOS mutagenesis; Y-family DNA polymerase; Mutagenesis; Translesion DNA synthesis ID SINGLE-STRANDED-DNA; MEDIATED TRANSLESION SYNTHESIS; UV-MUTAGENESIS; RECA PROTEIN; POL V; PROOFREADING FUNCTION; CYCLOBUTANE DIMER; SOS MUTAGENESIS; GROE MUTANTS; BETA-CLAMP AB Most damage induced mutagenesis in Escherichia coli is dependent upon the UmuD'C-2 protein complex, which comprises DNA polymerase V (pol V). Biochemical characterization of pol V has been hindered by the fact that the enzyme is notoriously difficult to purify, largely because overproduced UmuC is insoluble. Here, we report a simple and efficient protocol for the rapid purification of milligram quantities of pol V from just 4 L of bacterial culture. Rather than over producing the UmuC protein, it was expressed at low basal levels, while UmuD'(2) was expressed in trans from a high copy-number plasmid with an inducible promoter. We have also developed strategies to purify the beta-clamp and gamma-clamp loader free from contaminating polymerases. Using these highly purified proteins, we determined the cofactor requirements for optimal activity of pol V in vitro and found that pol V shows robust activity on an SSB-coated circular DNA template in the presence of the beta/gamma-complex and a RecA nucleoprotein filament (RecA*) formed in trans. This strong activity was attributed to the unexpectedly high processivity of pol V Mut (UmuD'C-2 . RecA . ATP), which was efficiently recruited to a primer terminus by SSB. Published by Elsevier B.V. C1 [Karata, Kiyonobu; Vaisman, Alexandra; Woodgate, Roger] NICHHD, Lab Genom Integr, NIH, Bethesda, MD 20892 USA. [Goodman, Myron F.] Univ So Calif, Dept Biol Sci, Los Angeles, CA 90089 USA. [Goodman, Myron F.] Univ So Calif, Dept Chem, Los Angeles, CA 90089 USA. RP Woodgate, R (reprint author), NICHHD, Lab Genom Integr, NIH, Bethesda, MD 20892 USA. EM woodgate@nih.gov RI Vaisman, Alexandra/C-3766-2013 OI Vaisman, Alexandra/0000-0002-2521-1467 FU National Institutes of Health/National Institute of Child Health and Human Development; National Institutes of Health [GM21422, ESO12259]; Japan Society for the Promotion of Science FX We thank Toshifumi Tomoyasu for providing us pBB280 and Charles McHenry for plasmids pTGCP.1.7 and pSJS9. This work was supported in part, by funds from the National Institutes of Health/National Institute of Child Health and Human Development Intramural Research Program to RW and National Institutes of Health [GM21422, ESO12259] to MFG. K.K. was also a recipient of a research fellowship from the Japan Society for the Promotion of Science. NR 48 TC 17 Z9 17 U1 0 U2 6 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 1568-7864 EI 1568-7856 J9 DNA REPAIR JI DNA Repair PD APR 1 PY 2012 VL 11 IS 4 BP 431 EP 440 DI 10.1016/j.dnarep.2012.01.012 PG 10 WC Genetics & Heredity; Toxicology SC Genetics & Heredity; Toxicology GA 929XS UT WOS:000303099600012 PM 22341652 ER PT J AU Izawa, K Hijikata, A Tanaka, N Kawai, T Saito, MK Goldbach-Mansky, R Aksentijevich, I Yasumi, T Nakahata, T Heike, T Nishikomori, R Ohara, O AF Izawa, Kazushi Hijikata, Atsushi Tanaka, Naoko Kawai, Tomoki Saito, Megumu K. Goldbach-Mansky, Raphaela Aksentijevich, Ivona Yasumi, Takahiro Nakahata, Tatsutoshi Heike, Toshio Nishikomori, Ryuta Ohara, Osamu TI Detection of Base Substitution-Type Somatic Mosaicism of the NLRP3 Gene with > 99.9% Statistical Confidence by Massively Parallel Sequencing SO DNA RESEARCH LA English DT Article DE next generation sequencing; mosaicism; DNA diagnosis; chronic infantile neurological cutaneous and articular syndrome ID MULTISYSTEM INFLAMMATORY DISEASE; ARTICULAR SYNDROME; CIAS1 MUTATIONS; GENOME; DEATH; CELLS AB Chronic infantile neurological cutaneous and articular syndrome (CINCA), also known as neonatal-onset multisystem inflammatory disease (NOMID), is a dominantly inherited systemic autoinflammatory disease and is caused by a heterozygous germline gain-of-function mutation in the NLRP3 gene. We recently found a high incidence of NLRP3 somatic mosaicism in apparently mutation-negative CINCA/NOMID patients using subcloning and subsequent capillary DNA sequencing. It is important to rapidly diagnose somatic NLRP3 mosaicism to ensure proper treatment. However, this approach requires large investments of time, cost, and labour that prevent routine genetic diagnosis of low-level somatic NLRP3 mosaicism. We developed a routine pipeline to detect even a low-level allele of NLRP3 with statistical significance using massively parallel DNA sequencing. To address the critical concern of discriminating a low-level allele from sequencing errors, we first constructed error rate maps of 14 polymerase chain reaction products covering the entire coding NLRP3 exons on a Roche 454 GS-FLX sequencer from 50 control samples without mosaicism. Based on these results, we formulated a statistical confidence value for each sequence variation in each strand to discriminate sequencing errors from real genetic variation even in a low-level allele, and thereby detected base substitutions at an allele frequency as low as 1% with 99.9% or higher confidence. C1 [Izawa, Kazushi; Tanaka, Naoko; Kawai, Tomoki; Yasumi, Takahiro; Heike, Toshio; Nishikomori, Ryuta] Kyoto Univ, Dept Pediat, Grad Sch Med, Sakyo Ku, Kyoto 6068507, Japan. [Hijikata, Atsushi; Ohara, Osamu] RIKEN Yokohama Inst, RIKEN Res Ctr Allergy & Immunol, Lab Immunogenom, Tarumi Ku, Yokohama, Kanagawa 2300045, Japan. [Saito, Megumu K.; Nakahata, Tatsutoshi] Kyoto Univ, Ctr iPS Cell Res & Applicat CiRA, Clin Applicat Dept, Kyoto, Japan. [Goldbach-Mansky, Raphaela] NIAMS, Translat Autoinflammatory Dis Sect, NIH, Bethesda, MD USA. [Aksentijevich, Ivona] NHGRI, Bethesda, MD 20892 USA. [Ohara, Osamu] Kazusa DNA Res Inst, Dept Human Genome Res, Kisarazu, Chiba 2920818, Japan. RP Nishikomori, R (reprint author), Kyoto Univ, Dept Pediat, Grad Sch Med, Sakyo Ku, 54 Shogoin, Kyoto 6068507, Japan. EM rnishiko@kuhp.kyoto-u.ac.jp; ohara@kazusa.or.jp RI Ohara, Osamu/G-5448-2015 OI Ohara, Osamu/0000-0002-3328-9571 FU Japanese Ministry of Education, Science, Sports, and Culture; Japanese Ministry of Health, Labor, and Welfare FX This study was supported by the Japanese Ministry of Education, Science, Sports, and Culture, and the Japanese Ministry of Health, Labor, and Welfare. NR 28 TC 17 Z9 17 U1 0 U2 5 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 1340-2838 J9 DNA RES JI DNA Res. PD APR PY 2012 VL 19 IS 2 BP 143 EP 152 DI 10.1093/dnares/dsr047 PG 10 WC Genetics & Heredity SC Genetics & Heredity GA 932KN UT WOS:000303290100004 PM 22279087 ER PT J AU Sun, HM Tawa, G Wallqvist, A AF Sun, Hongmao Tawa, Gregory Wallqvist, Anders TI Classification of scaffold-hopping approaches SO DRUG DISCOVERY TODAY LA English DT Review ID CAMBRIDGE STRUCTURAL DATABASE; ANGIOTENSIN-II; RECEPTOR ANTAGONISTS; BIOLOGICAL-ACTIVITIES; DRUG DISCOVERY; COMBINATORIAL LIBRARIES; SIMILARITY SEARCHES; MEDICINAL CHEMISTRY; KINASE INHIBITORS; CRYSTAL-STRUCTURE AB The general goal of drug discovery is to identify novel compounds that are active against a preselected biological target with acceptable pharmacological properties defined by marketed drugs. Scaffold hopping has been widely applied by medicinal chemists to discover equipotent compounds with novel backbones that have improved properties. In this article we classify scaffold hopping into four major categories, namely heterocycle replacements, ring opening or closure, peptidomimetics and topology-based hopping. We review the structural diversity of original and final scaffolds with respect to each category. We discuss the advantages and limitations of small, medium and large-step scaffold hopping. Finally, we summarize software that is frequently used to facilitate different kinds of scaffold-hopping methods. C1 [Sun, Hongmao; Tawa, Gregory; Wallqvist, Anders] US Army Med Res & Mat Command, Biotechnol HPC Software Applicat Inst, Telemed & Adv Technol Res Ctr, Frederick, MD 21702 USA. RP Sun, HM (reprint author), NIH, NIH Ctr Translat Therapeut, 9800 Med Ctr Dr, Bethesda, MD 20892 USA. EM hongmao.sun@nih.gov OI wallqvist, anders/0000-0002-9775-7469 FU U.S. Department of Defense Threat Reduction Agency [TMTI0004_09_BH_T]; Department of Defense Biotechnology High Performance Computing Software Applications Institute FX Funding of this research was provided by the U.S. Department of Defense Threat Reduction Agency Grant TMTI0004_09_BH_T and the Department of Defense Biotechnology High Performance Computing Software Applications Institute. The opinions or assertions contained herein are the private views of the authors and are not to be construed as official or as reflecting the views of the U.S. Army or of the U.S. Department of Defense. NR 120 TC 65 Z9 65 U1 5 U2 44 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 1359-6446 J9 DRUG DISCOV TODAY JI Drug Discov. Today PD APR PY 2012 VL 17 IS 7-8 BP 310 EP 324 DI 10.1016/j.drudis.2011.10.024 PG 15 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 929XV UT WOS:000303099900006 PM 22056715 ER PT J AU Fishman, P Bar-Yehuda, S Liang, BT Jacobson, KA AF Fishman, Pnina Bar-Yehuda, Sara Liang, Bruce T. Jacobson, Kenneth A. TI Pharmacological and therapeutic effects of A(3) adenosine receptor agonists SO DRUG DISCOVERY TODAY LA English DT Review ID NF-KAPPA-B; TUMOR-GROWTH INHIBITION; COLON-CARCINOMA GROWTH; RHEUMATOID-ARTHRITIS; IB-MECA; BIOCHEMICAL-CHARACTERIZATION; MYOCARDIAL-ISCHEMIA; REPERFUSION INJURY; ENDOTOXEMIC MICE; CANCER-THERAPY AB The A(3) adenosine receptor (A(3)AR) coupled to G(i) (inhibitory regulative guanine nucleotide-binding protein) mediates anti-inflammatory, anticancer and anti-ischemic protective effects. The receptor is overexpressed in inflammatory and cancer cells, while low expression is found in normal cells, rendering the A(3)AR as a potential therapeutic target. Highly selective A(3)AR agonists have been synthesized and molecular recognition in the binding site has been characterized. In this article, we summarize preclinical and clinical human studies that demonstrate that A(3)AR agonists induce specific antiinflammatory and anticancer effects through a molecular mechanism that entails modulation of the Wnt and the NF-kappa B signal transduction pathways. At present, A(3)AR agonists are being developed for the treatment of inflammatory diseases, including rheumatoid arthritis (RA) and psoriasis; ophthalmic diseases such as dry eye syndrome and glaucoma; liver diseases such as hepatocellular carcinoma and hepatitis. C1 [Jacobson, Kenneth A.] NIDDK, Mol Recognit Sect, Bioorgan Chem Lab, NIH, Bethesda, MD 20892 USA. [Fishman, Pnina; Bar-Yehuda, Sara] Can Fite BioPharma Ltd, Kiryat Matalon, IL-49170 Petah Tiqwa, Israel. [Liang, Bruce T.] Univ Connecticut, Pat & Jim Calhoun Cardiol Ctr, Ctr Hlth, Farmington, CT 06030 USA. RP Jacobson, KA (reprint author), NIDDK, Mol Recognit Sect, Bioorgan Chem Lab, NIH, Bldg 8A,Rm B1A-19, Bethesda, MD 20892 USA. EM kajacobs@helix.nih.gov RI Ji, Haofeng/G-6206-2012; Jacobson, Kenneth/A-1530-2009 OI Jacobson, Kenneth/0000-0001-8104-1493 FU Intramural NIH HHS [ZIA DK031117-24] NR 77 TC 73 Z9 74 U1 3 U2 19 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 1359-6446 J9 DRUG DISCOV TODAY JI Drug Discov. Today PD APR PY 2012 VL 17 IS 7-8 BP 359 EP 366 DI 10.1016/j.drudis.2011.10.007 PG 8 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 929XV UT WOS:000303099900011 PM 22033198 ER PT J AU Iyer, MR Lee, YS Deschamps, JR Dersch, CM Rothman, RB Jacobson, AE Rice, KC AF Iyer, Malliga R. Lee, Yong Sok Deschamps, Jeffrey R. Dersch, Christina M. Rothman, Richard B. Jacobson, Arthur E. Rice, Kenner C. TI Probes for narcotic receptor mediated phenomena. 44. Synthesis of an N-substituted 4-hydroxy-5-(3-hydroxyphenyl)morphan with high affinity and selective mu-antagonist activity SO EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY LA English DT Article DE Osmium tetroxide mediated oxidation; Opioid receptor affinity; Opioid receptor efficacy; 5-(3-Hydroxyphenyl)-2-phenethyl-2-azabicyclo[3.3.1]nonan-4-ol synthesis; Energy minimization for molecular overlay; X-ray crystallographic structure ID AGONIST; 5-(3-HYDROXYPHENYL)-N-PHENYLETHYLMORPHAN; DERIVATIVES; MORPHINE AB A simple three-step synthesis of 5-(3-hydroxyphenyl)-2-methyl-2-azabicyclo[3.3.1]nonan-4-ol (3a) was achieved using an osmium tetroxide mediated oxidation of the known intermediate 6. A pyrrolidine-ring variant of 3a (3-(7-(hydroxymethyl)-6-methyl-6-azabicyclo[3.2.1]octan-1-yl)phenol (5)) was isolated when other routes were used. The epimeric hydroxy analogue 4a was synthesized by simple inversion of the stereochemistry at C-4. Both N-methyl (3a and 4a) and N-phenethyl (3b and 4b) derivatives were synthesized. The compounds were examined for their opioid receptor affinity and the N-phenethyl analogue 3b was found to have relatively weak affinity for the mu-opioid receptor (K-i = 74 nM). However, the N-phenethyl analogue of the C-4 epimer, 4b, had about 15 fold higher affinity than 3b and was selective for the mu-opioid receptor (K-i = 4.6 nM). Compound 4b was a moderately potent mu-opioid antagonist (K-e = 12 nM), as determined by [S-35]GTP-gamma-S assays. Compounds 3b and 4b were energy minimized at the level of B3LYP/6-31G*, and then overlaid onto the 5-phenylmorphan, the (1R,5R,9S)-(-)-enantiomer of 2b (Fig. 1) with the alpha or beta-OH group at the C-9 position. The spatial orientation of the hydroxyl moiety in 3b, 4b, 2a, and 2b is proposed to be the structural requirement for high p-opioid receptor binding affinity and their agonist or antagonist activity. The modest change in spatial position of the hydroxyl moiety, and not the N-substituent, induced the change from potent agonist to an antagonist of moderate potency. Published by Elsevier Masson SAS. C1 [Iyer, Malliga R.; Jacobson, Arthur E.; Rice, Kenner C.] NIDA, Drug Design & Synth Sect, Chem Biol Res Branch, Bethesda, MD 20892 USA. [Iyer, Malliga R.; Jacobson, Arthur E.; Rice, Kenner C.] NIAAA, NIH, Dept Hlth & Human Serv, Bethesda, MD 20892 USA. [Lee, Yong Sok] NIH, Ctr Mol Modeling, Div Computat Biosci, CIT,DHHS, Bethesda, MD 20892 USA. [Deschamps, Jeffrey R.] USN, Res Lab, Ctr Biomol Sci & Engn, Washington, DC 20375 USA. [Dersch, Christina M.; Rothman, Richard B.] NIDA, Clin Psychopharmacol Sect, Chem Biol Res Branch, Addict Res Ctr,NIH,Dept Hlth & Human Serv, Baltimore, MD 21224 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 OI Deschamps, Jeffrey/0000-0001-5845-0010 FU NIH of the National Institute on Drug Abuse (NIDA); National Institute of Alcohol Abuse and Alcoholism; NIH through the Center for Information Technology; NIDA through Naval Research Laboratory (NRL) [Y1-DA1101] FX The work of the Drug Design and Synthesis Section, CBRB, NIDA, & NIAAA, was supported by the NIH Intramural Research Programs of the National Institute on Drug Abuse (NIDA) and the National Institute of Alcohol Abuse and Alcoholism. The Clinical Psychopharmacology Section, CBRB, NIDA, was supported by the NIH Intramural Research Program of the National Institute on Drug Abuse (NIDA). We also thank Dr. Klaus Gawrisch and Dr. Walter Teague (Laboratory of Membrane Biochemistry and Biophysics. NIAAA, for NMR spectral data. The authors also express their thanks to Noel Whittaker and Dr. Herman Yeh, Laboratory of Analytical Chemistry, NIDDK, for mass spectral data and 1H NMR spectral data. The quantum chemical study utilized PC/LINUX clusters at the Center for Molecular Modeling of the NIH (http://cit.nih.gov), and this research was supported by the NIH Intramural Research Program through the Center for Information Technology. The X-ray crystallographic work was supported by NIDA through an Interagency Agreement #Y1-DA1101 with the Naval Research Laboratory (NRL). NR 13 TC 5 Z9 5 U1 0 U2 5 PU ELSEVIER FRANCE-EDITIONS SCIENTIFIQUES MEDICALES ELSEVIER PI PARIS PA 23 RUE LINOIS, 75724 PARIS, FRANCE SN 0223-5234 J9 EUR J MED CHEM JI Eur. J. Med. Chem. PD APR PY 2012 VL 50 BP 44 EP 54 DI 10.1016/j.ejmech.2012.01.025 PG 11 WC Chemistry, Medicinal SC Pharmacology & Pharmacy GA 932IP UT WOS:000303284400006 PM 22341895 ER PT J AU Villalba, JM de Cabo, R Alcain, FJ AF Villalba, Jose M. de Cabo, Rafael Alcain, Francisco J. TI A patent review of sirtuin activators: an update SO EXPERT OPINION ON THERAPEUTIC PATENTS LA English DT Review DE aging; metabolic diseases; resveratrol; sirtuin activators; sirtuins ID SMALL-MOLECULE ACTIVATORS; NICOTINAMIDE ADENINE-DINUCLEOTIDE; CALORIE RESTRICTION; LIFE-SPAN; HISTONE DEACETYLASE; GENE-EXPRESSION; SACCHAROMYCES-CEREVISIAE; MODIFIED RESVERATROL; MAMMALIAN-CELLS; SKELETAL-MUSCLE AB Introduction: Reversible acetylation is a key post-translational modification of target proteins. Sirtuin deacetylases represent the homolog of the yeast silent information regulator (SIR2). Although seven sirtuins have been found in mammals, all sirtuin activators described to date act through SIRT1. Areas covered: Areas covered in this paper include a review of the patent literature associated with SIRT1 activators, with a focus on therapeutic applications, primarily related to the use of pharmaceuticals and nutraceuticals containing resveratrol (RSV), and the development of second-generation activators unrelated to RSV. Also discussed is the current controversy over whether or not these molecules are actual SIRT1 activators. Expert opinion: Developing effective strategies to protect against diet-induced metabolic imbalance is necessary to fight against current obesity rates. The hypothalamus is a candidate for developing drugs that suppress SIRT1 degradation, as a strategy for treating metabolic syndrome. Deciphering the basic mechanism of activators is essential to develop effective strategies to alter sirtuin activity. This is true regardless of the apparent controversy of whether in vitro activation of SIRT1 is direct or not, depending on the experimental design, and whether sirtuins may play a major role in longevity. The numerous studies on their positive effects against age-related diseases, obesity and other metabolic disorders are still valid, promising to positively influence the development of treatments to improve human health. C1 [Alcain, Francisco J.] Univ Castilla La Mancha, Dept Ciencias Med, Fac Med, E-13071 Ciudad Real, Spain. [Villalba, Jose M.] Univ Cordoba, Fac Ciencias, Dept Biol Celular Fisiol & Inmunol, Cordoba 14014, Spain. [de Cabo, Rafael] NIA, NIH, Lab Expt Gerontol, Baltimore, MD 21224 USA. RP Alcain, FJ (reprint author), Univ Castilla La Mancha, Dept Ciencias Med, Fac Med, Campus Ciudad Real, E-13071 Ciudad Real, Spain. EM franciscoj.alcain@uclm.es RI de Cabo, Rafael/J-5230-2016; Alcain, Francisco /N-7503-2016; OI de Cabo, Rafael/0000-0002-3354-2442; Alcain, Francisco /0000-0002-6833-7940; , rafael/0000-0003-2830-5693 FU Universidad de Castilla la Mancha [GE20112221]; Junta de Comunidades de Castilla la Mancha [PPII11-0318-2669]; NIH [1R01AG028125-01A1]; Ministerio de Ciencia e Innovacion [BFU2011-23578]; Junta de Andalucia Proyectos de Excelencia [P09-CVI-4887]; Junta de Andalucia Proyectos Internacionales; Junta de Andalucia and University of Cordoba [BIO-276]; NIH/NIA FX Authors' work is supported by Grants: Universidad de Castilla la Mancha GE20112221, Junta de Comunidades de Castilla la Mancha PPII11-0318-2669 to Dr FJ Alcain and NIH 1R01AG028125-01A1, Ministerio de Ciencia e Innovacion BFU2011-23578, Junta de Andalucia Proyectos de Excelencia P09-CVI-4887, Junta de Andalucia Proyectos Internacionales and BIO-276 (Junta de Andalucia and University of Cordoba) to JM Villalba. Funding to R de Cabo was provided by the NIH/NIA Intramural Research Program. Rafael de Cabo has a cooperative research and development agreement with Sirtris/GSK. NR 98 TC 14 Z9 14 U1 0 U2 27 PU INFORMA HEALTHCARE PI LONDON PA TELEPHONE HOUSE, 69-77 PAUL STREET, LONDON EC2A 4LQ, ENGLAND SN 1354-3776 J9 EXPERT OPIN THER PAT JI Expert Opin. Ther. Patents PD APR PY 2012 VL 22 IS 4 BP 355 EP 367 DI 10.1517/13543776.2012.669374 PG 13 WC Chemistry, Medicinal; Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 921DK UT WOS:000302458000002 PM 22475539 ER PT J AU Wang, WX Corrigan-Cummins, M Hudson, J Maric, I Simakova, O Neelapu, SS Kwak, LW Janik, JE Gause, B Jaffe, ES Calvo, KR AF Wang, Weixin Corrigan-Cummins, Meghan Hudson, Justin Maric, Irina Simakova, Olga Neelapu, Sattva S. Kwak, Larry W. Janik, John E. Gause, Barry Jaffe, Elaine S. Calvo, Katherine R. TI MicroRNA profiling of follicular lymphoma identifies microRNAs related to cell proliferation and tumor response SO HAEMATOLOGICA-THE HEMATOLOGY JOURNAL LA English DT Article DE follicular lymphoma; miRNA; lymphomagenesis; tumor response ID GENE-EXPRESSION; DNA-DAMAGE; B-LYMPHOCYTES; TRANSLOCATION T(14/18); MALIGNANT-LYMPHOMA; CROSS-TALK; IN-VIVO; DIFFERENTIATION; ACTIVATION; TARGET AB Background MicroRNAs can play an important role in tumorigenesis through post-transcriptional regulation of gene expression, and are not well characterized in follicular lymphoma. Design and Methods MicroRNA profiles of enriched follicular lymphoma tumor cells from 16 patients were generated by assaying 851 human microRNAs. Tandem gene expression profiles were obtained for predicting microRNA targets. Results The expression of 133 microRNAs was significantly different (> 2-fold; P<0.05) between follicular lymphoma and follicular hyperplasia. Forty-four microRNAs in three groups generated a unique follicular lymphoma signature. Of these, ten microRNAs were increased (miR-193a-5p, -193b*, -345, -513b, -574-3p, -584, -663, -1287, -1295, and -1471), 11 microRNAs were decreased (miR-17*, -30a, -33a, -106a*, -141, -202, -205, -222, -301b, -431*, and -570), and 23 microRNAs formed a group that was increased in most cases of follicular lymphoma but showed lower expression in a subset of cases (let-7a, let-7f, miR-7-1*, -9, -9*, -20a, -20b, -30b, -96, -98, -194, -195, -221*, -374a, -374b, -451, -454, -502-3p, -532-3p, -664*, -1274a, -1274b, and -1260). Higher expression of this last group was associated with improved response to chemotherapy. Gene expression analysis revealed increased expression of MAPK1, AKT1, PRKCE, IL4R and DROSHA and decreased expression of CDKN1A/p21, SOCS2, CHEK1, RAD51, KLF4, BLIMP1 and IRF4 in follicular lymphoma. Functional studies indicated that CDKN1A/p21 and SOCS2 expression is directly regulated by miR-20a/-20b and miR-194, respectively. Conclusions Follicular lymphoma is characterized by a unique microRNA signature, containing a subset of microRNAs whose expression correlate with response to chemotherapy. miR-20a/b and miR-194 target CDKN1A and SOCS2 in follicular lymphoma, potentially contributing to tumor cell proliferation and survival. C1 [Wang, Weixin; Corrigan-Cummins, Meghan; Maric, Irina; Simakova, Olga; Calvo, Katherine R.] NIH, Dept Lab Med, Hematol Sect, Ctr Clin, Bethesda, MD 20892 USA. [Hudson, Justin] Howard Univ, Coll Med, Washington, DC USA. [Neelapu, Sattva S.; Kwak, Larry W.] Univ Texas MD Anderson Canc Ctr, Div Canc Med, Dept Lymphoma & Myeloma, Houston, TX 77030 USA. [Janik, John E.] NCI, Metab Branch, Bethesda, MD 20892 USA. [Gause, Barry] NCI, SAIC, Frederick, MD 21701 USA. [Jaffe, Elaine S.] NCI, Pathol Lab, Bethesda, MD 20892 USA. RP Calvo, KR (reprint author), NIH, Dept Lab Med, Hematol Sect, Ctr Clin, 10 Ctr Dr,Bldg 10-2C306, Bethesda, MD 20892 USA. EM calvok@mail.nih.gov RI Calvo, Katherine/A-8109-2009; OI Calvo, Katherine/0000-0002-0771-4191; Jaffe, Elaine/0000-0003-4632-0301 FU NIH Clinical Center; Center for Cancer Research, NCI FX this work was supported by the Intramural Research Program of the NIH Clinical Center and the Center for Cancer Research, NCI. NR 52 TC 43 Z9 44 U1 0 U2 11 PU FERRATA STORTI FOUNDATION PI PAVIA PA VIA GIUSEPPE BELLI 4, 27100 PAVIA, ITALY SN 0390-6078 J9 HAEMATOL-HEMATOL J JI Haematol-Hematol. J. PD APR PY 2012 VL 97 IS 4 BP 586 EP 594 DI 10.3324/haematol.2011.048132 PG 9 WC Hematology SC Hematology GA 931TG UT WOS:000303241600021 PM 22102710 ER PT J AU Calvo, KR Hickstein, DD Holland, SM AF Calvo, Katherine R. Hickstein, Dennis D. Holland, Steven M. TI MonoMAC and GATA2 deficiency: overlapping clinical and pathological features with aplastic anemia and idiopathic CD4+ lymphocytopenia. Reply to Haematologica. 2012;97(4):058669 SO HAEMATOLOGICA-THE HEMATOLOGY JOURNAL LA English DT Letter DE MonoMac; GATA2; deficiency; diagnosis; aplastic anemia; ICL ID ACUTE MYELOID-LEUKEMIA; SPORADIC MONOCYTOPENIA; AUTOSOMAL-DOMINANT; PRIMARY LYMPHEDEMA; EMBERGER SYNDROME; MUTATIONS; MYELODYSPLASIA; CELL C1 [Calvo, Katherine R.] NIH, Dept Lab Med, Ctr Clin, Bethesda, MD 20892 USA. [Hickstein, Dennis D.] NCI, Bethesda, MD 20892 USA. [Holland, Steven M.] NIAID, Bethesda, MD 20892 USA. RP Calvo, KR (reprint author), NIH, Dept Lab Med, Ctr Clin, Bldg 10, Bethesda, MD 20892 USA. EM calvok@mail.nih.gov RI Calvo, Katherine/A-8109-2009 NR 13 TC 2 Z9 2 U1 0 U2 1 PU FERRATA STORTI FOUNDATION PI PAVIA PA VIA GIUSEPPE BELLI 4, 27100 PAVIA, ITALY SN 0390-6078 J9 HAEMATOL-HEMATOL J JI Haematol-Hematol. J. PD APR PY 2012 VL 97 IS 4 BP E12 EP E13 DI 10.3324/haematol.2012.063396 PG 2 WC Hematology SC Hematology GA 931TG UT WOS:000303241600002 ER PT J AU Adams, DK Nowakowski, NM Angerer, LA AF Adams, D. K. Nowakowski, N. M. Angerer, L. A. TI Evolution of food-induced developmental plasticity in echinoids SO INTEGRATIVE AND COMPARATIVE BIOLOGY LA English DT Meeting Abstract CT Annual Meeting of the Society-for-Integrative-and-Comparative-Biology (SICB) CY JAN 03-07, 2012 CL Charleston, SC SP Soc Integrat & Comparat Biol (SICB) C1 NIH, Bethesda, MD 20892 USA. American Univ, Washington, DC 20016 USA. EM adamsdi@mail.nih.gov RI Adams, Diane/E-7831-2015 OI Adams, Diane/0000-0001-6638-5781 NR 0 TC 0 Z9 0 U1 0 U2 2 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 1540-7063 J9 INTEGR COMP BIOL JI Integr. Comp. Biol. PD APR PY 2012 VL 52 SU 1 BP E202 EP E202 PG 1 WC Zoology SC Zoology GA 930TV UT WOS:000303165001273 ER PT J AU Adams, DK Sewell, MA Nowakowski, NM Angerer, LM AF Adams, D. K. Sewell, M. A. Nowakowski, N. M. Angerer, L. M. TI Mechanism underlying developmental plasticity in echinoid larval form SO INTEGRATIVE AND COMPARATIVE BIOLOGY LA English DT Meeting Abstract CT Annual Meeting of the Society-for-Integrative-and-Comparative-Biology (SICB) CY JAN 03-07, 2012 CL Charleston, SC SP Soc Integrat & Comparat Biol (SICB) C1 NIH, Bethesda, MD 20892 USA. Univ Auckland, Auckland 1, New Zealand. American Univ, Washington, DC 20016 USA. EM adamsdi@mail.nih.gov RI Adams, Diane/E-7831-2015 OI Adams, Diane/0000-0001-6638-5781 NR 0 TC 0 Z9 0 U1 0 U2 1 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 1540-7063 J9 INTEGR COMP BIOL JI Integr. Comp. Biol. PD APR PY 2012 VL 52 SU 1 BP E1 EP E1 PG 1 WC Zoology SC Zoology GA 930TV UT WOS:000303165000005 ER PT J AU Browne, WE Schnitzler, CE Gildea, D Nguyen, AD Maxwell, E Ryan, JF Baxevanis, AD AF Browne, W. E. Schnitzler, C. E. Gildea, D. Nguyen, A-D Maxwell, E. Ryan, J. F. Baxevanis, A. D. TI The Early Embryo: Genomic analysis of gene expression in an early diverging lineage of metazoans, the Ctenophora SO INTEGRATIVE AND COMPARATIVE BIOLOGY LA English DT Meeting Abstract CT Annual Meeting of the Society-for-Integrative-and-Comparative-Biology (SICB) CY JAN 03-07, 2012 CL Charleston, SC SP Soc Integrat & Comparat Biol (SICB) C1 [Browne, W. E.; Schnitzler, C. E.; Gildea, D.; Nguyen, A-D; Maxwell, E.; Ryan, J. F.; Baxevanis, A. D.] Univ Miami, NHGRI, NIH, Coral Gables, FL 33124 USA. EM wbrowne@bio.miami.edu RI Schnitzler, Christine/G-8733-2013 NR 0 TC 0 Z9 0 U1 0 U2 3 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 1540-7063 J9 INTEGR COMP BIOL JI Integr. Comp. Biol. PD APR PY 2012 VL 52 SU 1 BP E21 EP E21 PG 1 WC Zoology SC Zoology GA 930TV UT WOS:000303165000083 ER PT J AU Haspel, G Schwartz, A Soares, D AF Haspel, G. Schwartz, A. Soares, D. TI Unique mechanosensory adaptation to extreme environments in cavefish SO INTEGRATIVE AND COMPARATIVE BIOLOGY LA English DT Meeting Abstract CT Annual Meeting of the Society-for-Integrative-and-Comparative-Biology (SICB) CY JAN 03-07, 2012 CL Charleston, SC SP Soc Integrat & Comparat Biol (SICB) C1 [Haspel, G.; Schwartz, A.; Soares, D.] Univ Maryland, NINDS, College Pk, MD 20742 USA. EM daphne.soares@gmail.com NR 0 TC 0 Z9 0 U1 0 U2 6 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 1540-7063 J9 INTEGR COMP BIOL JI Integr. Comp. Biol. PD APR PY 2012 VL 52 SU 1 BP E259 EP E259 PG 1 WC Zoology SC Zoology GA 930TV UT WOS:000303165001501 ER PT J AU Ryan, JF Pang, K Schnitzler, CE Nguyen, AD Moreland, RT Havlak, P Putnam, NH Nisc Wolfsberg, TG Mullikin, JC Martindale, MQ Baxevanis, AD AF Ryan, J. F. Pang, K. Schnitzler, C. E. Nguyen, A-D Moreland, R. T. Havlak, P. Putnam, N. H. Nisc Wolfsberg, T. G. Mullikin, J. C. Martindale, M. Q. Baxevanis, A. D. TI The Genome of the Ctenophore, Mnemiopsis leidyi: Insights into the Origins of Morphological Complexity SO INTEGRATIVE AND COMPARATIVE BIOLOGY LA English DT Meeting Abstract CT Annual Meeting of the Society-for-Integrative-and-Comparative-Biology (SICB) CY JAN 03-07, 2012 CL Charleston, SC SP Soc Integrat & Comparat Biol (SICB) C1 NHGRI, NIH, Bethesda, MD 20892 USA. Univ Hawaii, Honolulu, HI 96822 USA. Rice Univ, Houston, TX 77251 USA. EM andy@mail.nih.gov RI Schnitzler, Christine/G-8733-2013 NR 0 TC 0 Z9 0 U1 0 U2 8 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 1540-7063 J9 INTEGR COMP BIOL JI Integr. Comp. Biol. PD APR PY 2012 VL 52 SU 1 BP E150 EP E150 PG 1 WC Zoology SC Zoology GA 930TV UT WOS:000303165001068 ER PT J AU Grespan, R Lemos, HP Carregaro, V Verri, WA Souto, FO de Oliveira, CJF Teixeira, C Ribeiro, JM Valenzuela, JG Cunha, FQ AF Grespan, Renata Lemos, Henrique P. Carregaro, Vanessa Verri, Waldiceu A., Jr. Souto, Fabricio O. de Oliveira, Carlo J. F. Teixeira, Clarissa Ribeiro, Jose Marcos Valenzuela, Jesus G. Cunha, Fernando Q. TI The protein LJM 111 from Lutzomyia longipalpis Salivary Gland Extract (SGE) accounts for the SGE-inhibitory effects upon inflammatory parameters in experimental arthritis model SO INTERNATIONAL IMMUNOPHARMACOLOGY LA English DT Article DE LJM 111 protein; Salivary gland extract; Arthritis; Chemotaxis ID TUMOR-NECROSIS-FACTOR; COLLAGEN-INDUCED ARTHRITIS; ANTIGEN-INDUCED ARTHRITIS; SAND FLY SALIVA; EXPERIMENTAL AUTOIMMUNE ENCEPHALOMYELITIS; COUPLED RECEPTOR KINASES; NF-KAPPA-B; DENDRITIC CELLS; RHEUMATOID-ARTHRITIS; FACTOR-ALPHA AB Several studies have pointed out the immunomodulatory properties of the Salivary Gland Extract (SGE) from Lutzomyia longipalpis. We aimed to identify the SGE component (s) responsible for its effect on ovalbumin (OVA)-induced neutrophil migration (NM) and to evaluate the effect of SGE and components in the antigen-induced arthritis (AIA) model. We tested the anti-arthritic activities of SGE and the recombinant LJM111 salivary protein (rLJM111) by measuring the mechanical hypernociception and the NM into synovial cavity. Furthermore, we measured IL-17, TNF-alpha and IFN-gamma released by lymph nodes cells stimulated with mBSA or anti-CD3 using enzyme-linked immunosorbent assay (ELISA). Additionally, we tested the effect of SGE and rLJM111 on co-stimulatory molecules expression (MHC-II and CD-86) by flow cytometry. TNF-alpha and IL-10 production (ELISA) of bone marrow-derived dendritic cells (BMDCs) stimulated with LPS, chemotaxis and actin polymerization from neutrophils. Besides, the effect of SGE on CXCR2 and GRK-2 expression on neutrophils was investigated. We identified one plasmid expressing the protein LJM111 that prevented NM in OVA-challenged immunized mice. Furthermore, both SGE and rLJM111 inhibited NM and pain sensitivity in AIA and reduced IL-17, TNF-alpha and IFN-gamma. SGE and rLJM111 also reduced MHC-II and CD-86 expression and TNF-alpha whereas increased IL-10 release by LPS-stimulated BMDCs. SGE, but not LJM 111, inhibited neutrophils chemotaxis and actin polymerization. Additionally, SGE reduced neutrophil CXCR2 expression and increased GRK-2. Thus, rLJM111 is partially responsible for SGE mechanisms by diminishing DC function and maturation but not chemoattraction of neutrophils. (C) 2012 Elsevier B.V. All rights reserved. C1 [Grespan, Renata; Lemos, Henrique P.; Verri, Waldiceu A., Jr.; Cunha, Fernando Q.] Univ Sao Paulo, Fac Med Ribeirao Preto, Dept Pharmacol, Ribeirao Preto, SP, Brazil. [Carregaro, Vanessa; Souto, Fabricio O.; de Oliveira, Carlo J. F.] Univ Sao Paulo, Fac Med Ribeirao Preto, Dept Immunol & Biochem, Ribeirao Preto, SP, Brazil. [Verri, Waldiceu A., Jr.] Univ Estadual Londrina, Ctr Biol Sci, Dept Pathol, Londrina, PR, Brazil. [Teixeira, Clarissa; Ribeiro, Jose Marcos; Valenzuela, Jesus G.] NIAID, Lab Malaria & Vector Res, NIH, Rockville, MD USA. RP Grespan, R (reprint author), Univ Sao Paulo, Dept Pharmacol, Fac Med Ribeirao Preto, Ave Bandeirantes 3900, BR-14049900 Sao Paulo, Brazil. EM r_grespan@yahoo.com.br RI Carregaro, Vanessa/D-2913-2012; Souto, Fabricio/I-3071-2013; Ribeiro, Jose/J-7011-2015; Verri, Waldiceu/I-1330-2013; Cunha, Fernando/M-3090-2014; OI Souto, Fabricio/0000-0002-2392-8499; Verri, Waldiceu/0000-0003-2756-9283; Cunha, Fernando Queiroz/0000-0003-4755-1670; Ribeiro, Jose/0000-0002-9107-0818 FU Intramural NIH HHS [ZIA AI000932-09] NR 68 TC 6 Z9 6 U1 1 U2 6 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 1567-5769 J9 INT IMMUNOPHARMACOL JI Int. Immunopharmacol. PD APR PY 2012 VL 12 IS 4 BP 603 EP 610 DI 10.1016/j.intimp.2012.02.004 PG 8 WC Immunology; Pharmacology & Pharmacy SC Immunology; Pharmacology & Pharmacy GA 930MP UT WOS:000303143800009 PM 22366405 ER PT J AU Dale, W Mohile, SG Eldadah, BA Trimble, EL Schilsky, RL Cohen, HJ Muss, HB Schmader, KE Ferrell, B Extermann, M Nayfield, SG Hurria, A AF Dale, William Mohile, Supriya G. Eldadah, Basil A. Trimble, Edward L. Schilsky, Richard L. Cohen, Harvey J. Muss, Hyman B. Schmader, Kenneth E. Ferrell, Betty Extermann, Martine Nayfield, Susan G. Hurria, Arti CA Canc & Aging Res Grp TI Biological, Clinical, and Psychosocial Correlates at the Interface of Cancer and Aging Research SO JNCI-JOURNAL OF THE NATIONAL CANCER INSTITUTE LA English DT Editorial Material ID COMPREHENSIVE GERIATRIC ASSESSMENT; ACUTE MYELOID-LEUKEMIA; QUALITY-OF-LIFE; OLDER-ADULTS; BREAST-CANCER; PROSTATE-CANCER; UNITED-STATES; ADJUVANT CHEMOTHERAPY; CELLULAR SENESCENCE; PERFORMANCE STATUS AB In September 2010, the Cancer and Aging Research Group, in collaboration with the National Cancer Institute and the National Institute on Aging, conducted the first of three planned conferences to discuss research methodology to generate the highest quality research in older adults with cancer and then disseminate these findings among those working in the fields of cancer and aging. Conference speakers discussed the current level of research evidence in geriatric oncology, outlined the current knowledge gaps, and put forth principles for research designs and strategies that would address these gaps within the next 10 years. It was agreed that future oncology research trials that enroll older adults should include: 1) improved standardized geriatric assessment of older oncology patients, 2) substantially enhanced biological assessment of older oncology patients, 3) specific trials for the most vulnerable and/or those older than 75 years, and 4) research infrastructure that specifically targets older adults and substantially strengthened geriatrics and oncology research collaborations. This initial conference laid the foundation for the next two meetings, which will address the research designs and collaborations needed to enhance therapeutic and intervention trials in older adults with cancer. C1 [Hurria, Arti] City Hope Natl Med Ctr, Dept Med Oncol & Therapeut Res, Duarte, CA 91010 USA. [Dale, William] Univ Chicago, Dept Med, Sect Geriatr & Palliat Med, Chicago, IL 60637 USA. [Schilsky, Richard L.] Univ Chicago, Sect Hematol Oncol, Chicago, IL 60637 USA. [Mohile, Supriya G.] Univ Rochester, James P Wilmot Canc Ctr, Dept Med Hematol Oncol, Rochester, NY USA. [Eldadah, Basil A.] NIA, Div Geriatr & Clin Gerontol, Bethesda, MD 20892 USA. [Trimble, Edward L.] NCI, Ctr Global Hlth, Bethesda, MD 20892 USA. [Nayfield, Susan G.] Univ Florida, Dept Aging & Geriatr Res, Gainesville, FL USA. [Cohen, Harvey J.] Duke Univ, Ctr Study Aging & Human Dev, Durham, NC USA. [Schmader, Kenneth E.] Duke Univ, Dept Geriatr Med, Durham, NC USA. [Muss, Hyman B.] Univ N Carolina, Dept Med, Chapel Hill, NC USA. [Muss, Hyman B.] Univ N Carolina, Lineberger Comprehens Canc Ctr, Chapel Hill, NC 27599 USA. [Ferrell, Betty] Durham Vet Affairs Med, Geriatr Res Educ Ctr, Durham, NC USA. [Ferrell, Betty] Durham Vet Affairs Med, Clin Ctr, Durham, NC USA. [Extermann, Martine] Univ S Florida, H Lee Moffitt Canc Ctr, Senior Adult Oncol Program, Tampa, FL 33682 USA. RP Hurria, A (reprint author), City Hope Natl Med Ctr, Dept Med Oncol & Therapeut Res, Duarte, CA 91010 USA. EM ahurria@coh.org FU NCATS NIH HHS [UL1 TR000064]; NCI NIH HHS [7U10-CA31946-29]; NCRR NIH HHS [KL2 RR024136]; NIA NIH HHS [R01 AG037037, U13 AG038151] NR 57 TC 31 Z9 31 U1 0 U2 5 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0027-8874 EI 1460-2105 J9 JNCI-J NATL CANCER I JI JNCI-J. Natl. Cancer Inst. PD APR PY 2012 VL 104 IS 8 BP 581 EP 589 DI 10.1093/jnci/djs145 PG 9 WC Oncology SC Oncology GA 930TE UT WOS:000303162400008 PM 22457474 ER PT J AU Schlom, J AF Schlom, Jeffrey TI Therapeutic Cancer Vaccines: Current Status and Moving Forward SO JNCI-JOURNAL OF THE NATIONAL CANCER INSTITUTE LA English DT Review ID COLONY-STIMULATING FACTOR; CELL LUNG-CANCER; RESISTANT PROSTATE-CANCER; LONG-TERM SURVIVAL; REGULATORY T-CELLS; CYCLOOXYGENASE-2 INHIBITOR CELECOXIB; METASTATIC COLORECTAL-CANCER; TUMOR-ASSOCIATED ANTIGENS; CHRONIC VIRAL-INFECTION; HIGH-DOSE INTERLEUKIN-2 AB Concurrent with US Food and Drug Administration (FDA) approval of the first therapeutic cancer vaccine, a wide spectrum of other cancer vaccine platforms that target a diverse range of tumor-associated antigens is currently being evaluated in randomized phase II and phase III trials. The profound influence of the tumor microenvironment and other immunosuppressive entities, however, can limit the effectiveness of these vaccines. Numerous strategies are currently being evaluated both preclinically and clinically to counteract these immunosuppressive entities, including the combined use of vaccines with immune checkpoint inhibitors, certain chemotherapeutics, small-molecule targeted therapies, and radiation. The potential influence of the appropriate patient population and clinical trial endpoint in vaccine therapy studies is discussed, as well as the potential importance of biomarkers in future directions of this field. C1 NCI, Lab Tumor Immunol & Biol, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. RP Schlom, J (reprint author), NCI, Lab Tumor Immunol & Biol, Ctr Canc Res, NIH, 10 Ctr Dr,Rm 8B09, Bethesda, MD 20892 USA. EM js141c@nih.gov FU Center for Cancer Research, National Cancer Institute, National Institutes of Health FX This study was supported by the Intramural Research Program of the Center for Cancer Research, National Cancer Institute, National Institutes of Health. NR 208 TC 124 Z9 129 U1 4 U2 46 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0027-8874 EI 1460-2105 J9 JNCI-J NATL CANCER I JI JNCI-J. Natl. Cancer Inst. PD APR PY 2012 VL 104 IS 8 BP 599 EP 613 DI 10.1093/jnci/djs033 PG 15 WC Oncology SC Oncology GA 930TE UT WOS:000303162400010 PM 22395641 ER PT J AU Kane, JM Hill, LD Kinon, BJ Potter, WZ Rapaport, MH Schooler, NR AF Kane, John M. Hill, Lauren D. Kinon, Bruce J. Potter, William Z. Rapaport, Mark H. Schooler, Nina R. TI New Clinical Drug Evaluation Unit (NCDEU) Annual Meeting: A Great Opportunity for Early Career Psychiatrists SO JOURNAL OF CLINICAL PSYCHIATRY LA English DT Editorial Material C1 [Kane, John M.] Zucker Hillside Hosp, Glen Oaks, NY 11004 USA. [Kane, John M.] Hofstra N Shore LIJ Sch Med, Glen Oaks, NY USA. [Hill, Lauren D.] NIMH, Div Serv & Intervent Res, Bethesda, MD 20892 USA. [Kinon, Bruce J.] Eli Lilly & Co, Indianapolis, IN 46285 USA. [Rapaport, Mark H.] Emory Univ, Dept Psychiat & Behav Sci, Atlanta, GA 30322 USA. [Schooler, Nina R.] Georgetown Univ, Dept Psychiat, Washington, DC USA. [Schooler, Nina R.] Vet Affairs Capitol Hlth Care Network, Mental Illness Res Educ & Clin Ctr, Washington, DC USA. RP Kane, JM (reprint author), Zucker Hillside Hosp, 75-59 263rd St,Kaufmann Bldg,Ste 103, Glen Oaks, NY 11004 USA. EM psychiatry@nshs.edu NR 0 TC 0 Z9 0 U1 0 U2 0 PU PHYSICIANS POSTGRADUATE PRESS PI MEMPHIS PA P O BOX 752870, MEMPHIS, TN 38175-2870 USA SN 0160-6689 J9 J CLIN PSYCHIAT JI J. Clin. Psychiatry PD APR PY 2012 VL 73 IS 4 BP 504 EP 505 DI 10.4088/JCP.12com07750 PG 2 WC Psychology, Clinical; Psychiatry SC Psychology; Psychiatry GA 932PU UT WOS:000303303800016 PM 22579149 ER PT J AU Matos, A Duque, V Luxo, C Melico-Silvestre, A Major, EO AF Matos, Ana Duque, Vitor Luxo, Cristina Melico-Silvestre, Antonio Major, Eugene O. TI Individuals infected with JC polyomavirus do not present detectable JC virus DNA in oropharyngeal fluids SO JOURNAL OF GENERAL VIROLOGY LA English DT Article ID PROGRESSIVE MULTIFOCAL LEUKOENCEPHALOPATHY; EPSTEIN-BARR-VIRUS; BK-VIRUS; CYTOMEGALOVIRUS-INFECTION; HUMAN-POPULATIONS; HEALTHY-ADULTS; URBAN SEWAGE; TRANSMISSION; EXCRETION; PREVALENCE AB JC virus (JCV) is ubiquitous in the human population. Primary infection normally occurs during childhood and is followed by a lifelong persistent infection. The main mode of transmission remains unknown. Several authors have hypothesized that JCV transmission occurs through the respiratory route, and that respiratory secretions could represent a possible source of viral particles. The present study intended to evaluate oropharyngeal fluids from patients infected with JCV, in order to ascertain if respiratory secretions could indeed constitute a source of exposure to this polyomavirus. Oropharyngeal washing samples from 25 patients co-infected with JCV and human immunodeficiency virus type 1 were evaluated for the presence of JCV DNA. Regardless of the titre of antibodies or the presence of viral urinary excretion, JCV genome was not detected in oropharyngeal samples collected from any of the patients infected with JCV included in this study, which may suggest that oropharyngeal fluids are an unlikely source for JCV infection. C1 [Matos, Ana; Luxo, Cristina] Univ Coimbra, Ctr Pharmaceut Studies, Fac Pharm, Coimbra, Portugal. [Duque, Vitor; Melico-Silvestre, Antonio] Coimbras Univ Hosp, Virol Lab, Dept Infect Dis, Coimbra, Portugal. [Major, Eugene O.] NINDS, Lab Mol Med & Neurosci, NIH, Bethesda, MD 20892 USA. RP Matos, A (reprint author), Univ Coimbra, Ctr Pharmaceut Studies, Fac Pharm, Coimbra, Portugal. EM anamatos@ci.uc.pt OI Matos, Ana Miguel/0000-0001-5764-0023; Luxo Maia, Paula Cristina/0000-0002-4676-5258 FU Center for Pharmaceutical Studies of the Portuguese Foundation for Science and Technology through POCTI (FEDER) FX The authors are grateful to the Center for Pharmaceutical Studies of the Portuguese Foundation for Science and Technology through POCTI (FEDER) for financial support. NR 45 TC 3 Z9 3 U1 2 U2 5 PU SOC GENERAL MICROBIOLOGY PI READING PA MARLBOROUGH HOUSE, BASINGSTOKE RD, SPENCERS WOODS, READING RG7 1AG, BERKS, ENGLAND SN 0022-1317 EI 1465-2099 J9 J GEN VIROL JI J. Gen. Virol. PD APR PY 2012 VL 93 BP 692 EP 697 DI 10.1099/vir.0.036798-0 PN 4 PG 6 WC Biotechnology & Applied Microbiology; Virology SC Biotechnology & Applied Microbiology; Virology GA 929OF UT WOS:000303074500002 PM 22158878 ER PT J AU Brooke, CB Schafer, A Matsushima, GK White, LJ Johnston, RE AF Brooke, Christopher B. Schaefer, Alexandra Matsushima, Glenn K. White, Laura J. Johnston, Robert E. TI Early activation of the host complement system is required to restrict central nervous system invasion and limit neuropathology during Venezuelan equine encephalitis virus infection SO JOURNAL OF GENERAL VIROLOGY LA English DT Article ID WEST-NILE-VIRUS; INDUCED DISEASE; SINDBIS VIRUS; HUMORAL RESPONSES; DENDRITIC CELLS; CDNA-CLONE; IN-VITRO; RECEPTOR; CLEARANCE; PATHOGENESIS AB Venezuelan equine encephalitis virus (VEEV) is a mosquito-borne RNA virus of the genus Alpha virus, family Togaviridae, that is responsible for sporadic outbreaks in human and equid populations in Central and South America. In order to ascertain the role that complement plays in resolving VEEV-induced disease, complement-deficient C3(-/-) were infected with a VEEV mutant (V3533) that caused mild, transient disease in immunocompetent mice. In the absence of a functional complement system, peripheral inoculation with V3533 induced much more severe encephalitis. This enhanced pathology was associated with a delay in clearance of infectious virus from the serum and more rapid invasion of the central nervous system in C3(-/-) mice. If V3533 was inoculated directly into the brain, however, disease outcome in C3(-/-) and wild-type mice was identical. These findings indicate that complement-dependent enhancement of peripheral virus clearance is critical for protecting against the development of severe VEEV-induced encephalitis. C1 [Brooke, Christopher B.; Schaefer, Alexandra; Matsushima, Glenn K.; White, Laura J.; Johnston, Robert E.] Univ N Carolina, Dept Microbiol & Immunol, Chapel Hill, NC 27599 USA. [Brooke, Christopher B.; Schaefer, Alexandra; White, Laura J.; Johnston, Robert E.] Univ N Carolina, Carolina Vaccine Inst, Chapel Hill, NC 27599 USA. [Matsushima, Glenn K.] Univ N Carolina, UNC Neurosci Ctr, Chapel Hill, NC 27599 USA. RP Brooke, CB (reprint author), NIAID, Cell Biol Sect, Viral Dis Lab, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA. EM brookecb@niaid.nih.gov FU NIH [U01AI070976, 5T32AI007419] FX This research was supported by NIH research grant U01AI070976. C. B. B. was supported by NIH training grant 5T32AI007419. We thank members of the Carolina Vaccine Institute for helpful discussions. We also thank Janice Weaver at the LCCC/DLAM University of North Carolina at Chapel Hill histopathology core facility. NR 58 TC 3 Z9 3 U1 0 U2 2 PU SOC GENERAL MICROBIOLOGY PI READING PA MARLBOROUGH HOUSE, BASINGSTOKE RD, SPENCERS WOODS, READING RG7 1AG, BERKS, ENGLAND SN 0022-1317 J9 J GEN VIROL JI J. Gen. Virol. PD APR PY 2012 VL 93 BP 797 EP 806 DI 10.1099/vir.0.038281-0 PN 4 PG 10 WC Biotechnology & Applied Microbiology; Virology SC Biotechnology & Applied Microbiology; Virology GA 929OF UT WOS:000303074500014 PM 22205717 ER PT J AU Lam, TTY Zhu, HC Smith, DK Guan, Y Holmes, EC Pybus, OG AF Lam, Tommy Tsan-Yuk Zhu, Huachen Smith, David K. Guan, Yi Holmes, Edward C. Pybus, Oliver G. TI The recombinant origin of emerging human norovirus GII.4/2008: intra-genotypic exchange of the capsid P2 domain SO JOURNAL OF GENERAL VIROLOGY LA English DT Article ID ACUTE GASTROENTERITIS; VARIANT; EMERGENCE; CHILDREN; VIRUS; KOREA; ALGORITHM; EVOLUTION; STRAINS; SEASONS AB GII.4 noroviruses are a major cause of acute gastroenteritis in humans. A new variant of GII.4, the 2008 variant, has recently increased its prevalence on a global scale. A previous study of this variant in Japan suggested that it might be of recombinant origin, with a breakpoint at the ORF1-ORF2 junction. Here, examination of the evolutionary origin of the 2008 variant based on a larger sample of worldwide GII.4 norovirus sequences revealed a more complex pattern of recombination between the 2006a- and 2006b-like variants of genotype GII.4, involving the P2 antigenic domain. Double (termed '2008i' and triple (termed '2008ii') recombinant forms of 2008 variants were identified. This study highlights the possible importance of intra-genotypic recombination over antigenic regions in driving norovirus evolution, and is suggestive of a process analogous to the antigenic shift of influenza A virus by reassortment. C1 [Lam, Tommy Tsan-Yuk; Pybus, Oliver G.] Univ Oxford, Dept Zool, Oxford OX1 3PS, England. [Lam, Tommy Tsan-Yuk; Zhu, Huachen; Smith, David K.; Guan, Yi] Shantou Univ Med Coll, Int Inst Infect & Immun, Shantou, Guangdong, Peoples R China. [Lam, Tommy Tsan-Yuk; Zhu, Huachen; Smith, David K.; Guan, Yi] Univ Hong Kong, State Key Lab Emerging Infect Dis, Li Ka Shing Fac Med, Hong Kong, Hong Kong, Peoples R China. [Holmes, Edward C.] Penn State Univ, Dept Biol, Ctr Infect Dis, University Pk, PA 16802 USA. [Holmes, Edward C.] NIH, Fogarty Int Ctr, Bethesda, MD 20892 USA. RP Lam, TTY (reprint author), Univ Oxford, Dept Zool, S Parks Rd, Oxford OX1 3PS, England. EM tylam.tommy@gmail.com RI Lam, Tommy Tsan-Yuk/D-4837-2012; Zhu, Huachen/A-8252-2017; OI Zhu, Huachen/0000-0003-2711-0501; Pybus, Oliver/0000-0002-8797-2667; Holmes, Edward/0000-0001-9596-3552 FU Royal Society; Li Ka Shing Foundation; Research Grant Council of Hong Kong SAR [HKU 765809M]; Royal Society, UK FX T. T.-Y. L. is supported by Newton International Fellowship from Royal Society. H. Z., D. K. S. and Y. G. are supported by Li Ka Shing Foundation and Research Grant Council of Hong Kong SAR (HKU 765809M). O. G. P. is supported by Royal Society, UK. Additional bioinformatic and computational resources were provided by the Computer Centre at The University of Hong Kong (HKU). We thank the two anonymous reviewers for useful suggestions. We also thank W. K. Kwan, Frankie Cheung and Lilian Chan (HKU) for technical support. NR 36 TC 11 Z9 11 U1 0 U2 2 PU SOC GENERAL MICROBIOLOGY PI READING PA MARLBOROUGH HOUSE, BASINGSTOKE RD, SPENCERS WOODS, READING RG7 1AG, BERKS, ENGLAND SN 0022-1317 J9 J GEN VIROL JI J. Gen. Virol. PD APR PY 2012 VL 93 BP 817 EP 822 DI 10.1099/vir.0.039057-0 PN 4 PG 6 WC Biotechnology & Applied Microbiology; Virology SC Biotechnology & Applied Microbiology; Virology GA 929OF UT WOS:000303074500016 PM 22238233 ER PT J AU Barrett, L Trehanpati, N Poonia, S Sarin, SK Polis, MA Masur, H Kottilil, S AF Barrett, L. Trehanpati, N. Poonia, S. Sarin, S. K. Polis, M. A. Masur, H. Kottilil, S. TI HEPATIC COMPARTMENTALIZATION OF EXHAUSTED REGULATORY CELLS IN CHRONIC HEPATITIS C PATIENTS SO JOURNAL OF HEPATOLOGY LA English DT Meeting Abstract CT 47th Annual Meeting of the European-Association-for-the-Study-of-the-Liver (EASL) CY APR 18-22, 2012 CL Barcelona, SPAIN SP European Assoc Study Liver (EASL) C1 [Barrett, L.; Poonia, S.; Polis, M. A.; Masur, H.; Kottilil, S.] NIAID, Immunoregulat Lab, NIH, Bethesda, MD 20892 USA. [Trehanpati, N.; Sarin, S. K.] ILBS, New Delhi, India. EM barrettl@niaid.nih.gov NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0168-8278 J9 J HEPATOL JI J. Hepatol. PD APR PY 2012 VL 56 SU 2 MA 821 BP S321 EP S321 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 931TD UT WOS:000303241301381 ER PT J AU Fuchs, C Claudel, T Kumari, P Stojakovic, T Halilbasic, E Spindelboek, W Gonzalez, F Trauner, M AF Fuchs, C. Claudel, T. Kumari, P. Stojakovic, T. Halilbasic, E. Spindelboek, W. Gonzalez, F. Trauner, M. TI FXR IS A KEY PLAYER IN NAFLD DEVELOPMENT BY CONTROLLING CHOP EXPRESSION SO JOURNAL OF HEPATOLOGY LA English DT Meeting Abstract CT 47th Annual Meeting of the European-Association-for-the-Study-of-the-Liver (EASL) CY APR 18-22, 2012 CL Barcelona, SPAIN SP European Assoc Study Liver (EASL) C1 [Fuchs, C.; Claudel, T.; Kumari, P.; Halilbasic, E.; Trauner, M.] Med Univ Vienna, Vienna, Austria. [Stojakovic, T.] Med Univ Graz, Clin Inst Med & Chem Lab Diagnost, Graz, Austria. [Gonzalez, F.] NCI, Lab Metab, Bethesda, MD 20892 USA. EM claudia.fuchs@stud.medunigraz.at NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0168-8278 J9 J HEPATOL JI J. Hepatol. PD APR PY 2012 VL 56 SU 2 MA 1236 BP S490 EP S490 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 931TD UT WOS:000303241302343 ER PT J AU Ghabril, M Bonkovsky, H Kum, C Davern, T Kleiner, D Serrano, J Hayashi, P Fontana, R Bonacini, M AF Ghabril, M. Bonkovsky, H. Kum, C. Davern, T. Kleiner, D. Serrano, J. Hayashi, P. Fontana, R. Bonacini, M. CA DILIN Coinvestigators TI LIVER INJURY FOLLOWING ANTI-TNF-ALPHA PEPTIDES: EXPERIENCE OF THE US DRUG-INDUCED LIVER INJURY NETWORK (DILIN) AND CRITICAL REVIEW OF PUBLISHED REPORTS SO JOURNAL OF HEPATOLOGY LA English DT Meeting Abstract CT 47th Annual Meeting of the European-Association-for-the-Study-of-the-Liver (EASL) CY APR 18-22, 2012 CL Barcelona, SPAIN SP European Assoc Study Liver (EASL) C1 [Ghabril, M.] Indiana Univ, Indianapolis, IN 46204 USA. [Bonkovsky, H.] Carolinas Med Ctr, Charlotte, NC 28203 USA. [Kum, C.; Davern, T.] CPMC, San Francisco, CA USA. [Kleiner, D.; Serrano, J.] NIH, Bethesda, MD 20892 USA. [Hayashi, P.] UNC, Chapel Hill, NC USA. [Fontana, R.] Univ Michigan, Ann Arbor, MI 48109 USA. [Bonacini, M.] Calif Pacific Med Ctr, San Francisco, CA USA. EM bonacim@sutterhealth.org NR 0 TC 0 Z9 1 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0168-8278 J9 J HEPATOL JI J. Hepatol. PD APR PY 2012 VL 56 SU 2 MA 1342 BP S528 EP S528 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 931TD UT WOS:000303241303017 ER PT J AU Govaere, O Komuta, M Spee, B Durnez, A Vander Borght, S Verslype, C Aerts, R Topal, B Pirenne, J Nevens, F Desmet, VJ Roberts, LR Thorgeirsson, SS Roskams, T AF Govaere, O. Komuta, M. Spee, B. Durnez, A. Vander Borght, S. Verslype, C. Aerts, R. Topal, B. Pirenne, J. Nevens, F. Desmet, V. J. Roberts, L. R. Thorgeirsson, S. S. Roskams, T. TI KERATIN19: A KEY ROLE PLAYER IN THE INVASION OF HUMAN HEPATOCELLULAR CARCINOMAS WITH PROGENITOR CELL FEATURES SO JOURNAL OF HEPATOLOGY LA English DT Meeting Abstract CT 47th Annual Meeting of the European-Association-for-the-Study-of-the-Liver (EASL) CY APR 18-22, 2012 CL Barcelona, SPAIN SP European Assoc Study Liver (EASL) C1 [Govaere, O.; Komuta, M.; Spee, B.; Durnez, A.; Vander Borght, S.; Desmet, V. J.; Roskams, T.] Katholieke Univ Leuven Hosp, Dept Morphol & Mol Pathol, Louvain, Belgium. [Verslype, C.; Nevens, F.] Katholieke Univ Leuven Hosp, Dept Hepatol, Louvain, Belgium. [Aerts, R.; Topal, B.] Katholieke Univ Leuven Hosp, Dept Abdominal Surg, Louvain, Belgium. [Pirenne, J.] Katholieke Univ Leuven Hosp, Dept Abdominal Transplant Surg, Louvain, Belgium. [Roberts, L. R.] Mayo Clin, Div Gastroenterol & Hepatol, Rochester, MN USA. [Thorgeirsson, S. S.] NCI, Expt Carcinogenesis Lab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. EM olivier.govaere@uzleuven.be NR 0 TC 0 Z9 0 U1 0 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0168-8278 J9 J HEPATOL JI J. Hepatol. PD APR PY 2012 VL 56 SU 2 MA 113 BP S50 EP S50 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 931TD UT WOS:000303241300114 ER PT J AU Guedj, J Rotman, Y Schmidt, P Albrecht, J Haynes-Williams, V Liang, JT Hoofnagle, JH Heller, T Dahari, H AF Guedj, J. Rotman, Y. Schmidt, P. Albrecht, J. Haynes-Williams, V. Liang, J. T. Hoofnagle, J. H. Heller, T. Dahari, H. TI MODELING HDV KINETICS DURING PEGYLATED INTERFERON-ALFA TREATMENT SO JOURNAL OF HEPATOLOGY LA English DT Meeting Abstract CT 47th Annual Meeting of the European-Association-for-the-Study-of-the-Liver (EASL) CY APR 18-22, 2012 CL Barcelona, SPAIN SP European Assoc Study Liver (EASL) C1 [Guedj, J.; Dahari, H.] Los Alamos Natl Lab, Los Alamos, NM USA. [Rotman, Y.; Haynes-Williams, V.; Liang, J. T.; Hoofnagle, J. H.; Heller, T.] NIDDK, Liver Dis Branch, NIH, Bethesda, MD USA. [Schmidt, P.; Albrecht, J.] Natl Inst Genet, Los Angeles, CA USA. [Dahari, H.] Univ Illinois, Chicago, IL USA. EM daharih@uic.edu NR 0 TC 0 Z9 0 U1 0 U2 3 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0168-8278 J9 J HEPATOL JI J. Hepatol. PD APR PY 2012 VL 56 SU 2 MA 507 BP S200 EP S200 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 931TD UT WOS:000303241301067 ER PT J AU Kohli, A Funk, E Burbelo, P Shivakumar, B Polis, M Masur, H Kottilil, S AF Kohli, A. Funk, E. Burbelo, P. Shivakumar, B. Polis, M. Masur, H. Kottilil, S. TI A NOVEL HCV-PROTEOME-WIDE LUCIFERASE IMMUNOPRECIPITATION ASSAY PREDICTIVE OF HCV TREATMENT OUTCOME SO JOURNAL OF HEPATOLOGY LA English DT Meeting Abstract CT 47th Annual Meeting of the European-Association-for-the-Study-of-the-Liver (EASL) CY APR 18-22, 2012 CL Barcelona, SPAIN SP European Assoc Study Liver (EASL) C1 [Kohli, A.; Funk, E.; Shivakumar, B.; Polis, M.; Kottilil, S.] NIAID, Bethesda, MD 20892 USA. [Burbelo, P.] NIDCR, Bethesda, MD USA. [Masur, H.] NIH, CCMD CC, Bethesda, MD 20892 USA. EM kohlia@niaid.nih.gov NR 0 TC 0 Z9 0 U1 0 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0168-8278 J9 J HEPATOL JI J. Hepatol. PD APR PY 2012 VL 56 SU 2 MA 1127 BP S444 EP S444 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 931TD UT WOS:000303241302234 ER PT J AU Marquardt, JU Maass, T Krupp, M Staib, F Gasier, T Andersen, JB Galle, PR Thorgeirsson, SS Teufel, A AF Marquardt, J. U. Maass, T. Krupp, M. Staib, F. Gasier, T. Andersen, J. B. Galle, P. R. Thorgeirsson, S. S. Teufel, A. TI MOLECULAR STAGES OF PDGFB DRIVEN LIVER FIBROSIS: LESONS FROM A TRANSGENIC MOUSE MODEL SO JOURNAL OF HEPATOLOGY LA English DT Meeting Abstract CT 47th Annual Meeting of the European-Association-for-the-Study-of-the-Liver (EASL) CY APR 18-22, 2012 CL Barcelona, SPAIN SP European Assoc Study Liver (EASL) C1 [Marquardt, J. U.; Maass, T.; Krupp, M.; Staib, F.; Galle, P. R.; Teufel, A.] Johannes Gutenberg Univ Mainz, Dept Med 1, D-6500 Mainz, Germany. [Marquardt, J. U.; Andersen, J. B.; Thorgeirsson, S. S.] NCI, Lab Expt Carcinogenesis, CCR, NIH, Bethesda, MD 20892 USA. [Gasier, T.] Univ Mannheim, Dept Pathol, Mannheim, Germany. EM marquarj@uni-mainz.de NR 0 TC 0 Z9 0 U1 1 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0168-8278 J9 J HEPATOL JI J. Hepatol. PD APR PY 2012 VL 56 SU 2 MA 385 BP S155 EP S155 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 931TD UT WOS:000303241300383 ER PT J AU Marquardt, JU Fischer, K Krupp, M Teufel, A Thorgeirsson, SS Galle, PR Strand, S AF Marquardt, J. U. Fischer, K. Krupp, M. Teufel, A. Thorgeirsson, S. S. Galle, P. R. Strand, S. TI INTEGRATIVE ANALYSIS OF SIRT6 REGULATED GENE NETWORKS IN THE DEVELOPMENT AND PROGRESSION OF HUMAN HEPATOCELLULAR CARCINOMA SO JOURNAL OF HEPATOLOGY LA English DT Meeting Abstract CT 47th Annual Meeting of the European-Association-for-the-Study-of-the-Liver (EASL) CY APR 18-22, 2012 CL Barcelona, SPAIN SP European Assoc Study Liver (EASL) C1 [Marquardt, J. U.; Fischer, K.; Krupp, M.; Teufel, A.; Galle, P. R.; Strand, S.] Johannes Gutenberg Univ Mainz, Dept Med 1, D-6500 Mainz, Germany. [Marquardt, J. U.; Thorgeirsson, S. S.] NCI, Expt Carcinogenesis Lab, CCR, NIH, Bethesda, MD 20892 USA. EM marquarj@uni-mainz.de NR 0 TC 0 Z9 0 U1 0 U2 2 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0168-8278 J9 J HEPATOL JI J. Hepatol. PD APR PY 2012 VL 56 SU 2 MA 290 BP S120 EP S120 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 931TD UT WOS:000303241300289 ER PT J AU Navarro, VJ Barnhart, HX Bonkovsky, HL Reddy, KR Seeff, L Serrano, J Talwalkar, JA Vega, M Vuppalanchi, R AF Navarro, V. J. Barnhart, H. X. Bonkovsky, H. L. Reddy, K. R. Seeff, L. Serrano, J. Talwalkar, J. A. Vega, M. Vuppalanchi, R. CA DILIN Investigators TI DIAGNOSING HEPATOTOXICITY ATTRIBUTABLE TO HERBAL & DIETARY SUPPLEMENTS (HDS): TEST-RETEST RELIABILITY OF A NOVEL CAUSALITY ASSESSMENT TOOL SO JOURNAL OF HEPATOLOGY LA English DT Meeting Abstract CT 47th Annual Meeting of the European-Association-for-the-Study-of-the-Liver (EASL) CY APR 18-22, 2012 CL Barcelona, SPAIN SP European Assoc Study Liver (EASL) C1 [Navarro, V. J.; Vega, M.] Thomas Jefferson Univ, Div Gastroenterol & Hepatol, Philadelphia, PA 19107 USA. [Barnhart, H. X.] Duke Clin Res Inst, Dept Biostat & Bioinformat, Durham, NC USA. [Bonkovsky, H. L.] Carolinas Med Ctr & HealthCare Syst, Charlotte, NC USA. [Reddy, K. R.] Univ Penn, Div Gastroenterol & Hepatol, Philadelphia, PA 19104 USA. [Seeff, L.] US FDA, Silver Spring, MD USA. [Serrano, J.] NIDDK, Div Digest Dis & Nutr, Bethesda, MD USA. [Talwalkar, J. A.] Mayo Clin, Rochester, MN USA. [Vuppalanchi, R.] Indiana Univ, Div Gastroenterol & Hepatol, Indianapolis, IN 46204 USA. EM victor.navarro@jefferson.edu NR 0 TC 3 Z9 3 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0168-8278 J9 J HEPATOL JI J. Hepatol. PD APR PY 2012 VL 56 SU 2 MA 1364 BP S536 EP S536 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 931TD UT WOS:000303241303039 ER PT J AU Boos, TL Cheng, KJ Greiner, E Deschamps, JR Jacobson, AE Rice, KC AF Boos, Terrence L. Cheng, Kejun Greiner, Elisabeth Deschamps, Jeffrey R. Jacobson, Arthur E. Rice, Kenner C. TI Configurational Reassignment and Improved Preparation of the Competitive IL-6 Receptor Antagonist 20R,21R-Epoxyresibufogenin-3-formate SO JOURNAL OF NATURAL PRODUCTS LA English DT Article ID BUFADIENOLIDES; INTERLEUKIN-6; RESIBUFOGENIN AB 20R,21R-Epoxyresibufogenin-3-formate (1) and 20S,21S-epoxyresibufogenin-3-formate (2) were synthesized from commercial resibufogenin (3) using known procedures. The major product (1) was dextrorotatory, as was the major product from the reported synthesis of epoxyresibufogenin-3-formate; however, the literature (+)-compound was assigned the 20S,21S-configuration on the basis of NMR data. We have now unequivocally determined, using single-crystal X-ray structure analyses of the major and minor products of the synthesis and of their derivatives, that the major product from the synthesis was (+)-20R,21R-epoxyresibufogenin-3-formate (1). Our minor synthetic product was determined to have the (-)-20S,21S-configuration (2). The (+)-20R,21R-compound 1 has been found to have high affinity for the IL-6 receptor and to act as an IL-6 antagonist. A greatly improved synthesis of 1 was achieved through oxidation of preformed resibufogenin-3-formate. This has enabled us to prepare, from the very expensive commercial resibufogenin, considerably larger quantities of 1, the only known nonpeptide small-molecule IL-6 antagonist. C1 [Boos, Terrence L.; Cheng, Kejun; Greiner, Elisabeth; Jacobson, Arthur E.; Rice, Kenner C.] NIDA, Drug Design & Synth Sect, Chem Biol Res Branch, Bethesda, MD 20892 USA. [Boos, Terrence L.; Cheng, Kejun; Greiner, Elisabeth; Jacobson, Arthur E.; Rice, Kenner C.] NIAAA, NIH, US Dept HHS, Bethesda, MD 20892 USA. [Deschamps, Jeffrey R.] USN, Ctr Biomol Sci & Engn, Res 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 OI Deschamps, Jeffrey/0000-0001-5845-0010 FU NIH of the National Institute of Diabetes and Digestive and Kidney Diseases; National Institute on Drug Abuse [Y1-DA1101]; National Institute of Alcohol Abuse and Alcoholism, NIH, DHHS; Naval Research Laboratory (NRL) FX This research was supported by the NIH Intramural Research Programs of the National Institute of Diabetes and Digestive and Kidney Diseases, the National Institute on Drug Abuse, and the National Institute of Alcohol Abuse and Alcoholism, NIH, DHHS. We thank N. Whittaker and Dr. J. Lloyd (Mass Spectrometry Facility, NIDDK) for the MS data and Drs. K. Gawrisch and W. Teague (Laboratory of Membrane Biochemistry and Biophysics, NIAAA) for NMR spectroscopic data. The X-ray crystallographic work was supported by NIDA through Interagency Agreement #Y1-DA1101 with the Naval Research Laboratory (NRL). NR 22 TC 3 Z9 3 U1 0 U2 5 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0163-3864 J9 J NAT PROD JI J. Nat. Prod. PD APR PY 2012 VL 75 IS 4 BP 661 EP 668 DI 10.1021/np2008957 PG 8 WC Plant Sciences; Chemistry, Medicinal; Pharmacology & Pharmacy SC Plant Sciences; Pharmacology & Pharmacy GA 931LD UT WOS:000303220500022 PM 22360661 ER PT J AU Li, J Fronczek, FR Ferreira, D Burandt, CL Setola, V Roth, BL Zjawiony, JK AF Li, Jun Fronczek, Frank R. Ferreira, Daneel Burandt, Charles L., Jr. Setola, Vincent Roth, Bryan L. Zjawiony, Jordan K. TI Bis-spirolabdane Diterpenoids from Leonotis nepetaefolia SO JOURNAL OF NATURAL PRODUCTS LA English DT Article ID LABDANE DITERPENOIDS; LEONURUS-SIBIRICUS; CONSTITUENTS; PERSICUS AB Ten new bis-spirolabdane diterpenoids, leonepetaefolins A-E (1, 3, 5, 7, 9) and 15-epi-leonepetaefolins A-E (2, 4, 6, 8, 10), together with eight known labdane diterpenoids (11-18) as well as two known flavonoids, apigenin and cirsiliol, were isolated from the leaves of Leonotis nepetaefolia. The structures of the new compounds were determined on the basis of ID- and 2D-NMR experiments including H-1, C-13, DEPT, H-1-H-1 COSY, HSQC, HMBC, and NOESY. The absolute configuration of an epimeric mixture of 1 and 2 was determined by X-ray crystallographic analysis. The compounds - isolated were evaluated for their binding propensity in several CNS G-protein-coupled receptor assays in vitro. C1 [Li, Jun; Ferreira, Daneel; Zjawiony, Jordan K.] Univ Mississippi, Sch Pharm, Dept Pharmacognosy, University, MS 38677 USA. [Ferreira, Daneel; Zjawiony, Jordan K.] Univ Mississippi, Sch Pharm, Res Inst Pharmaceut Sci, University, MS 38677 USA. [Fronczek, Frank R.] Louisiana State Univ, Dept Chem, Baton Rouge, LA 70803 USA. [Setola, Vincent; Roth, Bryan L.] Univ N Carolina, Sch Med, Dept Pharmacognosy, Chapel Hill, NC 27599 USA. [Setola, Vincent; Roth, Bryan L.] Univ N Carolina, NIMH Psychoact Drug Screening Program, Chapel Hill, NC 27599 USA. [Burandt, Charles L., Jr.] Univ Mississippi, Natl Ctr Nat Prod Res, University, MS 38677 USA. RP Zjawiony, JK (reprint author), Univ Mississippi, Sch Pharm, Dept Pharmacognosy, University, MS 38677 USA. EM jordan@olemiss.edu RI Roth, Bryan/F-3928-2010; Li, Jun /M-9884-2016 OI Li, Jun /0000-0001-8243-5267 FU National Institutes of Health [R03DA023491]; NIMH FX The project was financially supported by a grant from the National Institutes of Health (R03DA023491) and by the NIMH Psychoactive Drug Screening Program. The authors are grateful to Ms. B. Wang at the Department of Pharmacognosy for running the HRESIMS experiments. NR 37 TC 9 Z9 9 U1 0 U2 12 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0163-3864 J9 J NAT PROD JI J. Nat. Prod. PD APR PY 2012 VL 75 IS 4 BP 728 EP 734 DI 10.1021/np3000156 PG 7 WC Plant Sciences; Chemistry, Medicinal; Pharmacology & Pharmacy SC Plant Sciences; Pharmacology & Pharmacy GA 931LD UT WOS:000303220500032 PM 22475308 ER PT J AU Negus, SS Rosenberg, MB Altarifi, AA O'Connell, RH Folk, JE Rice, KC AF Negus, S. Stevens Rosenberg, Marisa B. Altarifi, Ahmad A. O'Connell, Robert H. Folk, John E. Rice, Kenner C. TI Effects of the Delta Opioid Receptor Agonist SNC80 on Pain-Related Depression of Intracranial Self-Stimulation (ICSS) in Rats SO JOURNAL OF PAIN LA English DT Article DE Pain; depression; delta opioid receptor; SNC80; ARM390 ID SPRAGUE-DAWLEY RATS; RHESUS-MONKEYS; ANTIDEPRESSANT-LIKE; MODEL; TOLERANCE; MORPHINE; MICE; INFLAMMATION; ANALGESICS; DEPENDENCE AB The delta opioid receptor agonist SNC80 produces both antinociceptive and antidepressant effects in rodents. This profile suggests that SNC80 may also reverse prodepressant effects of pain. Accordingly, this study compared SNC80 effects in complementary assays of pain-stimulated and pain-depressed behavior in rats. Intraperitoneal injection of dilute acid served as an acute noxious visceral stimulus in rats to stimulate abdominal stretching (a pain-stimulated behavior) or depress intracranial self-stimulation of the medial forebrain bundle (ICSS; a pain-depressed behavior). When administered once per week to minimize acute tolerance, SNC80 (1-10 mg/kg IP) decreased acid-stimulated stretching but had little effect on acid-induced depression of ICSS. More frequent SNC80 administration produced tolerance to SNC80 effects on acid-stimulated stretching, but unmasked antinociception in the assay of acid-depressed ICSS. SNC80 did not facilitate ICSS in the absence of pain, and effects of SNC80 were not duplicated by ARM390, a reputed delta agonist congener of SNC80 that does not internalize delta receptors. These findings support continued consideration of delta agonists as candidate analgesics to treat prodepressant effects of pain and illustrate the potential for diametrically opposite effects of drug treatments on preclinical measures of pain-stimulated and pain-depressed behavior. Perspective: The delta opioid agonist SNC80 blocked pain-related depression of intracranial self-stimulation in rats, suggesting that delta agonists may be useful to treat prodepressant effects of pain. Repeated SNC80 produced tolerance to SNC80 antinociception in a conventional assay of pain-stimulated behavior but unmasked SNC80 antinociception in an assay of pain-depressed behavior. (c) 2012 by the American Pain Society. Published by Elsevier Inc. All rights reserved C1 [Negus, S. Stevens; Rosenberg, Marisa B.; Altarifi, Ahmad A.; O'Connell, Robert H.] Virginia Commonwealth Univ, Dept Pharmacol & Toxicol, Richmond, VA 23220 USA. [Folk, John E.; Rice, Kenner C.] Natl Inst Drug Abuse, Chem Biol Res Branch, Bethesda, MD USA. [Folk, John E.; Rice, Kenner C.] NIAAA, NIH, DHHS, Bethesda, MD USA. RP Negus, SS (reprint author), Virginia Commonwealth Univ, Dept Pharmacol & Toxicol, 410 N 12th St, Richmond, VA 23220 USA. EM ssnegus@vcu.edu FU National Institute on Drug Abuse [R01-DA11460]; National Institute of Neurological Disorders and Stroke [R01-NS070715]; National Institute on Alcohol Abuse and Alcoholism FX Supported in part by R01-DA11460 from the National Institute on Drug Abuse and R01-NS070715 from the National Institute of Neurological Disorders and Stroke. A portion of this work was also supported by the Intramural Research Programs of the National Institute on Drug Abuse and the National Institute on Alcohol Abuse and Alcoholism. NR 44 TC 16 Z9 16 U1 0 U2 7 PU CHURCHILL LIVINGSTONE PI EDINBURGH PA JOURNAL PRODUCTION DEPT, ROBERT STEVENSON HOUSE, 1-3 BAXTERS PLACE, LEITH WALK, EDINBURGH EH1 3AF, MIDLOTHIAN, SCOTLAND SN 1526-5900 J9 J PAIN JI J. Pain PD APR PY 2012 VL 13 IS 4 BP 317 EP 327 DI 10.1016/j.jpain.2011.12.003 PG 11 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 932CK UT WOS:000303267800002 PM 22424913 ER PT J AU Carlson-Bremer, D Johnson, CK Miller, RH Gulland, FMD Conrad, PA Wasmuth, JD Colegrove, KM Grigg, ME AF Carlson-Bremer, Daphne Johnson, Christine K. Miller, Robin H. Gulland, Frances M. D. Conrad, Patricia A. Wasmuth, James D. Colegrove, Kathleen M. Grigg, Michael E. TI IDENTIFICATION OF TWO NOVEL COCCIDIAN SPECIES SHED BY CALIFORNIA SEA LIONS (ZALOPHUS CALIFORNIANUS) SO JOURNAL OF PARASITOLOGY LA English DT Article ID EIMERIA-PHOCAE; HARBOR SEALS; TOXOPLASMA-GONDII; VITULINA; APICOMPLEXA; EVOLUTION; SPOROZOA; OOCYSTS; MANATEE; SIRENIA AB Routine fecal examination revealed novel coccidian oocysts in asymptomatic California sea lions (Zalophus californianus) in a rehabilitation facility. Coccidian oocysts were observed in fecal samples collected from 15 of 410 California sea lions admitted to The Marine Mammal Center between April 2007 and October 2009. Phylogenetic analysis using the full ITS-1 region, partial small subunit 18S rDNA sequence, and the Apicomplexa rpoB region identified 2 distinct sequence clades, referred to as Coccidia A and Coccidia B, and placed them in the Sarcocystidae, grouped with the tissue-cyst forming coccidia. Both sequence clades resolved as individual taxa at ITS-1 and rpoB and were most closely related to Neospora caninum. Coccidia A was identified in 11 and Coccidia B in 4 of 12 sea lion oocyst samples successfully sequenced (3 of those sea lions were co-infected with both parasites). Shedding of Coccidia A oocysts was not associated with age class, sex, or stranding location, but yearlings represented the majority of shedders (8/15). This is the first study to use molecular phylogenetics to identify and describe coccidian parasites shed by a marine mammal. C1 [Carlson-Bremer, Daphne; Johnson, Christine K.; Miller, Robin H.; Gulland, Frances M. D.; Conrad, Patricia A.; Wasmuth, James D.; Colegrove, Kathleen M.; Grigg, Michael E.] Univ Calif Davis, Wildlife Hlth Ctr, Sch Vet Med, Davis, CA 95616 USA. RP Grigg, ME (reprint author), NIAID, Mol Parasitol Unit, Parasit Dis Lab, NIH, 4 Ctr Dr,Room B1-06, Bethesda, MD 20892 USA. EM griggm@niaid.nih.gov FU NSF-EID from the Ocean Sciences Division [OCE-1065990]; NIH [T32 RR07038]; NIAID; Canadian Institute for Advanced Research (CIFAR); Wildlife Health Center, School of Veterinary Medicine, University of California, Davis; The Marine Mammal Center FX This work was supported and funded in part by an NSF-EID grant from the Ocean Sciences Division, OCE-1065990, NIH Training Grant T32 RR07038, the Intramural Research Program of the NIH and NIAID, the Canadian Institute for Advanced Research (CIFAR) Integrated Microbial Biodiversity Program (MEG), the Wildlife Health Center, School of Veterinary Medicine, University of California, Davis, and The Marine Mammal Center. We would like to thank Liz Wheeler, Emily Andrews, Denise Greig, and all the volunteers at The Marine Mammal Center for their assistance in sample collection and transport. We also gratefully acknowledge Ann C. Melli, Andrea Packham, Samantha Hunt, and Aiko Adell for their assistance in the laboratory processing of samples. All samples used in this study were authorized by the National Marine Fisheries Service Research and Enhancement Permit to Take Marine Mammals (Permit No. 932-1489-08). Sarcocystis neurona monoclonal antibody was provided by Dr. Antoinette Marsh, University of Missouri College of Veterinary Medicine, Columbia, Missouri. Neospora caninum polyclonal antibody was obtained from the California Animal Health and Food Safety Laboratory, University of California, Davis, California. NR 37 TC 5 Z9 6 U1 0 U2 10 PU AMER SOC PARASITOLOGISTS PI LAWRENCE PA 810 EAST 10TH STREET, LAWRENCE, KS 66044 USA SN 0022-3395 J9 J PARASITOL JI J. Parasitol. PD APR PY 2012 VL 98 IS 2 BP 347 EP 354 DI 10.1645/GE-2752.1 PG 8 WC Parasitology SC Parasitology GA 932FL UT WOS:000303275700019 PM 22091999 ER PT J AU Klumpers, F Denys, D Kenemans, JL Grillon, C van der Aart, J Baas, JMP AF Klumpers, Floris Denys, Damiaan Kenemans, J. Leon Grillon, Christian van der Aart, Jasper Baas, Johanna M. P. TI Testing the effects of Delta 9-THC and D-cycloserine on extinction of conditioned fear in humans SO JOURNAL OF PSYCHOPHARMACOLOGY LA English DT Article DE Delta 9-THC; d-cycloserine; extinction; fear conditioning; fear-potentiated startle; human ID OBSESSIVE-COMPULSIVE DISORDER; RANDOMIZED CONTROLLED-TRIAL; SOCIAL ANXIETY DISORDER; AGONIST D-CYCLOSERINE; POTENTIATED STARTLE; EXPOSURE THERAPY; ENDOCANNABINOID SYSTEM; HEALTHY-VOLUNTEERS; MEMORY; FACILITATION AB Preclinical evidence implicates several neurotransmitter systems in the extinction of conditioned fear. These results are of great interest, because the reduction of acquired fear associations is critical in therapies for anxiety disorders. We tested whether findings with respect to the N-methyl-D-aspartate (NMDA) and cannabinoid receptor (CB) systems in animals carry over to healthy human subjects. To that end, we administered selected doses of D-cycloserine (partial NMDA receptor agonist, 250 mg), delta-9-tetrahydrocannabinol (THC, CB1 receptor agonist, 10 mg), or placebo prior to the extinction session of a 3-day conditioning protocol. D-cycloserine did not affect within-session extinction, or the retention of extinction in healthy human participants, in contrast with patient data but in line with previous reports in healthy volunteers. During extinction training, Delta 9-THC reduced conditioned skin conductance responses, but not fear-potentiated startle. This effect was not retained at the retention test 2 days later, suggesting it was dependent on acute effects of the drug. Our findings implicate that facilitation of the CB1 or NMDA system with the substances used in this study does not affect conditioned fear extinction lastingly in healthy humans. The apparent discrepancy between these findings and the results from (pre-)clinical trials is discussed in terms of room for improvement in these systems in healthy volunteers, and the lack of specificity of THC as a CB1 agonist. C1 [Baas, Johanna M. P.] Univ Utrecht, Dept Expt Psychol, Fac Social Sci, Helmholtz Inst, NL-3584 CS Utrecht, Netherlands. [Klumpers, Floris; Kenemans, J. Leon; Baas, Johanna M. P.] Univ Utrecht, Utrecht Inst Pharmaceut Sci, NL-3584 CS Utrecht, Netherlands. [Denys, Damiaan] Univ Amsterdam, Acad Med Ctr, Dept Psychiat, NL-1105 AZ Amsterdam, Netherlands. [Denys, Damiaan] Inst Neurosci, Amsterdam, Netherlands. [Grillon, Christian] NIMH, Mood & Anxiety Disorders Program, Bethesda, MD 20892 USA. RP Baas, JMP (reprint author), Univ Utrecht, Dept Expt Psychol, Fac Social Sci, Helmholtz Inst, Van Unnik Bldg,Heidelberglaan 2, NL-3584 CS Utrecht, Netherlands. EM j.m.p.baas@uu.nl RI Klumpers, Floris/J-2857-2012 FU NWO; NIMH FX This work was supported by a NWO Veni-grant awarded to JMPB, and by the NIMH Intramural Research Program (CG). NR 57 TC 21 Z9 22 U1 3 U2 8 PU SAGE PUBLICATIONS LTD PI LONDON PA 1 OLIVERS YARD, 55 CITY ROAD, LONDON EC1Y 1SP, ENGLAND SN 0269-8811 J9 J PSYCHOPHARMACOL JI J. Psychopharmacol. PD APR PY 2012 VL 26 IS 4 BP 471 EP 478 DI 10.1177/0269881111431624 PG 8 WC Clinical Neurology; Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA 930GQ UT WOS:000303126100005 PM 22351380 ER PT J AU Baranowski, T Islam, N Baranowski, J Martin, S Beltran, A Dadabhoy, H Adame, SH Watson, KB Thompson, D Cullen, KW Subar, AF AF Baranowski, Tom Islam, Noemi Baranowski, Janice Martin, Shelby Beltran, Alicia Dadabhoy, Hafza Adame, Su-heyla Watson, Kathleen B. Thompson, Debbe Cullen, Karen W. Subar, Amy F. TI Comparison of a Web-Based versus Traditional Diet Recall among Children SO JOURNAL OF THE ACADEMY OF NUTRITION AND DIETETICS LA English DT Article DE Diet assessment; Computer; 24-hour recall; Children ID 13-YEAR-OLD CHILDREN; FOOD-INTAKE; ACCURACY; NUTRITION; VALIDITY AB Self-administered instruments offer a low-cost diet assessment method for use in adult and pediatric populations. This study tested whether 8- to 13-year-old children could complete an early version of the Automated Self Administered 24-hour diet recall (ASA24) and how this compared to an interviewer-administered 24-hour diet recall. One-hundred twenty 8- to 13-year-old children were recruited in Houston from June through August 2009 and randomly assigned to complete either the ASA24 or an interviewer-administered 24-hour diet recall, followed by the other recall mode covering the same time interval. Multivariate analysis of variance, testing for differences by age, sex, and ethnic/racial group, were applied to percentages of food matches, intrusions, and omissions between reports on the ASA24 and the interviewer-administered 24-hour diet recall. For the ASA24, qualitative findings were reported regarding ease of use. Overall matches between interviewer-administered and ASA24 self-administered 24-hour diet recall was 47.8%. Matches were significantly lower among younger (8- to 9-year-old) compared with older (10- to 13-year-old) children. Omissions on ASA24 (18.9% overall) were most common among 8-year-olds and intermediate among 9-year-olds. Eight- and 9-year-olds had substantial difficulties and often required aid in completing ASA24. Findings from this study suggest that a simpler version of an Internet-based diet recall program would be easier for children to use. J Acad Nutr Diet. 2012;112:527-532. C1 [Baranowski, Tom; Islam, Noemi; Baranowski, Janice; Martin, Shelby; Beltran, Alicia; Dadabhoy, Hafza; Adame, Su-heyla; Watson, Kathleen B.; Thompson, Debbe; Cullen, Karen W.] Baylor Coll Med, USDA ARS, Childrens Nutr Res Ctr, Houston, TX 77030 USA. [Subar, Amy F.] NCI, Div Canc Control & Populat Sci, Appl Res Program, Risk Factor Monitoring & Methods Branch EPN, Bethesda, MD 20892 USA. RP Baranowski, T (reprint author), Baylor Coll Med, USDA ARS, Childrens Nutr Res Ctr, 1100 Bates St, Houston, TX 77030 USA. EM tbaranow@bcm.edu OI Baranowski, Tom/0000-0002-0653-2222 FU National Cancer Institute [5 U01 CA130762-04]; USDA/ARS [58-6250-6001] FX This research was primarily funded by a grant from the National Cancer Institute (5 U01 CA130762-04). This work is also a publication of the United States Department of Agriculture (USDA/ARS) Children's Nutrition Research Center, Department of Pediatrics, Baylor College of Medicine, Houston, TX, and had been funded in part with federal funds from the USDA/ARS under Cooperative Agreement No. 58-6250-6001. The contents of this publication do not necessarily reflect the views or policies of the USDA, nor does mention of trade names, commercial products, or organizations imply endorsement from the US government. NR 24 TC 22 Z9 22 U1 0 U2 16 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 2212-2672 J9 J ACAD NUTR DIET JI J. Acad. Nutr. Diet. PD APR PY 2012 VL 112 IS 4 BP 527 EP 532 DI 10.1016/j.jada.2011.10.002 PG 6 WC Nutrition & Dietetics SC Nutrition & Dietetics GA 930WR UT WOS:000303175900010 PM 22717216 ER PT J AU Amiri-Kordestani, L Fojo, T AF Amiri-Kordestani, Laleh Fojo, Tito TI Why Do Phase III Clinical Trials in Oncology Fail so Often? SO JOURNAL OF THE NATIONAL CANCER INSTITUTE LA English DT Editorial Material ID DRUG DEVELOPMENT; TARGETED AGENTS; STABLE DISEASE; END-POINT; CHEMOTHERAPY; SURVIVAL; CANCER; BENEFIT; DESIGNS C1 [Amiri-Kordestani, Laleh; Fojo, Tito] NCI, Med Oncol Branch, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. RP Fojo, T (reprint author), NCI, Med Oncol Branch, Ctr Canc Res, NIH, Bldg 10,Rm 12N226,9000 Rockville Pike, Bethesda, MD 20892 USA. EM fojot@mail.nih.gov NR 19 TC 17 Z9 17 U1 1 U2 2 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 APR PY 2012 VL 104 IS 8 BP 568 EP 569 DI 10.1093/jnci/djs180 PG 2 WC Oncology SC Oncology GA 930TE UT WOS:000303162400001 PM 22491346 ER PT J AU Lee, C Kim, KP Long, DJ Bolch, WE AF Lee, Choonsik Kim, Kwang Pyo Long, Daniel J. Bolch, Wesley E. TI Organ doses for reference pediatric and adolescent patients undergoing computed tomography estimated by Monte Carlo simulation SO MEDICAL PHYSICS LA English DT Article ID HYBRID COMPUTATIONAL PHANTOMS; TUBE CURRENT MODULATION; CT EXAMINATIONS; FEMALE; FEASIBILITY; DOSIMETRY; MODELS AB Purpose: To establish an organ dose database for pediatric and adolescent reference individuals undergoing computed tomography (CT) examinations by using Monte Carlo simulation. The data will permit rapid estimates of organ and effective doses for patients of different age, gender, examination type, and CT scanner model. Methods: The Monte Carlo simulation model of a Siemens Sensation 16 CT scanner previously published was employed as a base CT scanner model. A set of absorbed doses for 33 organs/tissues normalized to the product of 100 mAs and CTDIvol (mGy/100 mAs mGy) was established by coupling the CT scanner model with age-dependent reference pediatric hybrid phantoms. A series of single axial scans from the top of head to the feet of the phantoms was performed at a slice thickness of 10 mm, and at tube potentials of 80, 100, and 120 kVp. Using the established CTDIvol- and 100 mAs-normalized dose matrix, organ doses for different pediatric phantoms undergoing head, chest, abdomen-pelvis, and chest-abdomen-pelvis (CAP) scans with the Siemens Sensation 16 scanner were estimated and analyzed. The results were then compared with the values obtained from three independent published methods: CT-Expo software, organ dose for abdominal CT scan derived empirically from patient abdominal circumference, and effective dose per dose-length product (DLP). Results: Organ and effective doses were calculated and normalized to 100 mAs and CTDIvol for different CT examinations. At the same technical setting, dose to the organs, which were entirely included in the CT beam coverage, were higher by from 40 to 80% for newborn phantoms compared to those of 15-year phantoms. An increase of tube potential from 80 to 120 kVp resulted in 2.5-2.9-fold greater brain dose for head scans. The results from this study were compared with three different published studies and/or techniques. First, organ doses were compared to those given by CT-Expo which revealed dose differences up to several-fold when organs were partially included in the scan coverage. Second, selected organ doses from our calculations agreed to within 20% of values derived from empirical formulae based upon measured patient abdominal circumference. Third, the existing DLP-to-effective dose conversion coefficients tended to be smaller than values given in the present study for all examinations except head scans. Conclusions: A comprehensive organ/effective dose database was established to readily calculate doses for given patients undergoing different CT examinations. The comparisons of our results with the existing studies highlight that use of hybrid phantoms with realistic anatomy is important to improve the accuracy of CT organ dosimetry. The comprehensive pediatric dose data developed here are the first organ-specific pediatric CT scan database based on the realistic pediatric hybrid phantoms which are compliant with the reference data from the International Commission on Radiological Protection (ICRP). The organ dose database is being coupled with an adult organ dose database recently published as part of the development of a user-friendly computer program enabling rapid estimates of organ and effective dose doses for patients of any age, gender, examination types, and CT scanner model. (C) 2012 American Association of Physicists in Medicine. [http://dx.doi.org/10.1118/1.3693052] C1 [Lee, Choonsik] NCI, Div Canc Epidemiol & Genet, NIH, Bethesda, MD 20852 USA. [Kim, Kwang Pyo] Kyung Hee Univ, Dept Nucl Engn, Gyeonggi Do 446906, South Korea. [Long, Daniel J.; Bolch, Wesley E.] Univ Florida, J Crayton Pruitt Family Dept Biomed Engn, Gainesville, FL 32611 USA. RP Lee, C (reprint author), NCI, Div Canc Epidemiol & Genet, NIH, Bethesda, MD 20852 USA. EM leechoonsik@mail.nih.gov RI Lee, Choonsik/C-9023-2015 OI Lee, Choonsik/0000-0003-4289-9870 FU Radiation Epidemiology Branch of the National Cancer Institute [HHS-N2612-0090-0098P, HHS-N2612-0100-0692P, HHS-N2612-0090-0177P] FX This work was supported by Contract Nos. HHS-N2612-0090-0098P, HHS-N2612-0100-0692P, and HHS-N2612-0090-0177P with the Radiation Epidemiology Branch of the National Cancer Institute. NR 28 TC 39 Z9 40 U1 1 U2 8 PU AMER ASSOC PHYSICISTS MEDICINE AMER INST PHYSICS PI MELVILLE PA STE 1 NO 1, 2 HUNTINGTON QUADRANGLE, MELVILLE, NY 11747-4502 USA SN 0094-2405 J9 MED PHYS JI Med. Phys. PD APR PY 2012 VL 39 IS 4 BP 2129 EP 2146 DI 10.1118/1.3693052 PG 18 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 919ZY UT WOS:000302371900042 PM 22482634 ER PT J AU Ashizawa, T Perlman, S Gomez, C Wilmot, G Schmahmann, J Ying, S Zesiewicz, T Paulson, H Shakkottai, V Bushara, K Mazzoni, P Kuo, SH Pulst, S Figueroa, K Xia, GB Krischer, J Cuthbertson, D Holbert, AR Ferguson, J Galpern, W Subramony, S AF Ashizawa, Tetsuo Perlman, Susan Gomez, Christopher Wilmot, George Schmahmann, Jeremy Ying, Sarah Zesiewicz, Theresa Paulson, Henry Shakkottai, Vikram Bushara, Khalaf Mazzoni, Pietro Kuo, Sheng-Han Pulst, Stefan Figueroa, Karla Xia, Guangbin Krischer, Jeffrey Cuthbertson, David Holbert, Amy Roberts Ferguson, John Galpern, Wendy Subramony, S. TI Clinical Characteristics of Spinocerebellar Ataxias 1, 2, 3 and 6 SO NEUROLOGY LA English DT Meeting Abstract CT 64th Annual Meeting of the American-Academy-of-Neurology (AAN) CY APR 21-28, 2012 CL New Orleans, LA SP Amer Acad Neurol (AAN) C1 [Ashizawa, Tetsuo] Univ Florida, McKnight Brain Inst UF, Gainesville, FL USA. [Perlman, Susan] Univ Calif Los Angeles, Sherman Oaks, CA USA. [Gomez, Christopher] Univ Chicago, Chicago, IL 60637 USA. [Wilmot, George] Emory Univ, Atlanta, GA 30322 USA. [Zesiewicz, Theresa; Krischer, Jeffrey; Cuthbertson, David; Holbert, Amy Roberts] Univ S Florida, Tampa, FL USA. [Pulst, Stefan; Figueroa, Karla] Univ Utah, Salt Lake City, UT USA. [Paulson, Henry; Shakkottai, Vikram] Univ Michigan, Ann Arbor, MI 48109 USA. [Schmahmann, Jeremy] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Ying, Sarah] Jons Hopkins Univ, Baltimore, MD USA. [Bushara, Khalaf] Univ Minnesota, Minneapolis, MN USA. [Mazzoni, Pietro; Kuo, Sheng-Han] Columbia Univ, New York, NY USA. [Ferguson, John] NIH, Off Rare Dis, Bethesda, MD 20892 USA. [Galpern, Wendy] NINDS, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0028-3878 J9 NEUROLOGY JI Neurology PD APR PY 2012 VL 78 SU 1 MA S12002 PG 3 WC Clinical Neurology SC Neurosciences & Neurology GA 931GQ UT WOS:000303204804266 ER PT J AU Benninger, D Dukart, J Von Meyenburg, J Thees, S Bassetti, C Waldvogel, D Kollias, S Iseki, K Draganski, B AF Benninger, David Dukart, Juergen Von Meyenburg, Jan Thees, Sebastian Bassetti, Claudio Waldvogel, Daniel Kollias, Spyridon Iseki, Kazumi Draganski, Bogdan TI Progressive Cortical Degeneration in Parkinson's Disease SO NEUROLOGY LA English DT Meeting Abstract CT 64th Annual Meeting of the American-Academy-of-Neurology (AAN) CY APR 21-28, 2012 CL New Orleans, LA SP Amer Acad Neurol (AAN) C1 [Benninger, David] CHUV, Dept Neurol, Lausanne, Switzerland. [Von Meyenburg, Jan; Thees, Sebastian] Inst Neuroradiol, Zurich, Switzerland. [Bassetti, Claudio] Neuroctr Svizzera Italiana, Lugano, Switzerland. [Waldvogel, Daniel] Univ Zurich Hosp, Dept Neurol, CH-8091 Zurich, Switzerland. [Kollias, Spyridon] Dept Neuroradiol, Zurich, Switzerland. [Iseki, Kazumi] NINDS, Bethesda, MD 20892 USA. RI Kollias, Spyros/J-9276-2012; Dukart, Juergen/E-5459-2011; Benninger, David/A-8157-2015; Draganski, Bogdan/C-3096-2016 OI Benninger, David/0000-0002-1049-9533; Draganski, Bogdan/0000-0002-5159-5919 NR 0 TC 0 Z9 0 U1 1 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0028-3878 J9 NEUROLOGY JI Neurology PD APR PY 2012 VL 78 SU 1 MA P01214 PG 1 WC Clinical Neurology SC Neurosciences & Neurology GA 931GQ UT WOS:000303204800316 ER PT J AU Bette, S Liaghat, J De la Plata, CM Diaz-Arrastia, R AF Bette, Sagari Liaghat, John De la Plata, Carlos Marquez Diaz-Arrastia, Ramon TI Examination of Functional Connectivity Networks in Traumatic Brain Injury SO NEUROLOGY LA English DT Meeting Abstract CT 64th Annual Meeting of the American-Academy-of-Neurology (AAN) CY APR 21-28, 2012 CL New Orleans, LA SP Amer Acad Neurol (AAN) C1 [Bette, Sagari; Liaghat, John; De la Plata, Carlos Marquez] UT SW Med Ctr, Dallas, TX USA. [Diaz-Arrastia, Ramon] NIH, Rockville, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0028-3878 J9 NEUROLOGY JI Neurology PD APR PY 2012 VL 78 SU 1 MA P01181 PG 1 WC Clinical Neurology SC Neurosciences & Neurology GA 931GQ UT WOS:000303204800259 ER PT J AU Bette, S Liaghat, J De la Plata, CM Diaz-Arrastia, R AF Bette, Sagari Liaghat, John De la Plata, Carlos Marquez Diaz-Arrastia, Ramon TI Examination of Functional Connectivity Networks in Traumatic Brain Injury SO NEUROLOGY LA English DT Meeting Abstract CT 64th Annual Meeting of the American-Academy-of-Neurology (AAN) CY APR 21-28, 2012 CL New Orleans, LA SP Amer Acad Neurol (AAN) C1 [Bette, Sagari; Liaghat, John; De la Plata, Carlos Marquez] UT SW Med Ctr, Dallas, TX USA. [Diaz-Arrastia, Ramon] NIH, Rockville, MD USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0028-3878 J9 NEUROLOGY JI Neurology PD APR PY 2012 VL 78 SU 1 MA IN61007 PG 2 WC Clinical Neurology SC Neurosciences & Neurology GA 931GQ UT WOS:000303204800108 ER PT J AU Bhanushali, M Kranick, S Inati, S Freeman, A Battiwalla, M Nath, A AF Bhanushali, Minal Kranick, Sarah Inati, Sara Freeman, Alexandra Battiwalla, Minoo Nath, Avindra TI Herpes Virus Infections of the Brain Complicating Allogeneic Hematopoietic Stem Cell Transplantation (SCT) SO NEUROLOGY LA English DT Meeting Abstract CT 64th Annual Meeting of the American-Academy-of-Neurology (AAN) CY APR 21-28, 2012 CL New Orleans, LA SP Amer Acad Neurol (AAN) C1 [Bhanushali, Minal; Inati, Sara] NINDS, NIH, Bethesda, MD 20892 USA. [Kranick, Sarah] NINDS, NIH, Brookeville, MD USA. [Freeman, Alexandra] NIAID, NIH, Bethesda, MD 20892 USA. [Battiwalla, Minoo] NHLBI, NIH, Bethesda, MD 20892 USA. [Nath, Avindra] Natl Inst Neurol Disorders & Stroke, NIH, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0028-3878 J9 NEUROLOGY JI Neurology PD APR PY 2012 VL 78 SU 1 MA S57001 PG 2 WC Clinical Neurology SC Neurosciences & Neurology GA 931GQ UT WOS:000303204803199 ER PT J AU Bosch, EP Tracy, J Goodman, B Dyck, PJB Toro, C Giannini, C AF Bosch, E. Peter Tracy, Jennifer Goodman, Brent Dyck, P. James B. Toro, Camilo Giannini, Caterina TI Facial Onset Sensory and Motor Neuronopathy: A Neurodegenerative TDP-43 Proteinopathy? SO NEUROLOGY LA English DT Meeting Abstract CT 64th Annual Meeting of the American-Academy-of-Neurology (AAN) CY APR 21-28, 2012 CL New Orleans, LA SP Amer Acad Neurol (AAN) C1 [Bosch, E. Peter; Goodman, Brent] Mayo Clin Arizona, Scottsdale, AZ USA. [Tracy, Jennifer; Dyck, P. James B.; Giannini, Caterina] Mayo Clin, Rochester, MN USA. [Toro, Camilo] NHGRI, NIH, Frederick, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0028-3878 J9 NEUROLOGY JI Neurology PD APR PY 2012 VL 78 SU 1 MA IN91010 PG 2 WC Clinical Neurology SC Neurosciences & Neurology GA 931GQ UT WOS:000303204803064 ER PT J AU Bosch, EP Tracy, J Goodman, B Dyck, PJB Toro, C Giannini, C AF Bosch, E. Peter Tracy, Jennifer Goodman, Brent Dyck, P. James B. Toro, Camilo Giannini, Caterina TI Facial Onset Sensory and Motor Neuronopathy: A Neurodegenerative TDP-43 Proteinopathy? SO NEUROLOGY LA English DT Meeting Abstract CT 64th Annual Meeting of the American-Academy-of-Neurology (AAN) CY APR 21-28, 2012 CL New Orleans, LA SP Amer Acad Neurol (AAN) C1 [Bosch, E. Peter; Goodman, Brent] Mayo Clin Arizona, Scottsdale, AZ USA. [Tracy, Jennifer; Dyck, P. James B.; Giannini, Caterina] Mayo Clin, Rochester, MN USA. [Toro, Camilo] NHGRI, NIH, Frederick, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0028-3878 J9 NEUROLOGY JI Neurology PD APR PY 2012 VL 78 SU 1 MA P03183 PG 2 WC Clinical Neurology SC Neurosciences & Neurology GA 931GQ UT WOS:000303204801287 ER PT J AU Calvo, A Borghero, G Cannas, A Marrosu, M Murru, M Floris, G Traynor, B Renton, A Moglia, C Canosa, A Ilardi, A Cammarosano, S Brunetti, M Ossola, I Restagno, G Chio, A AF Calvo, Andrea Borghero, Giuseppe Cannas, Antonino Marrosu, Maria Murru, Maria Floris, Gianluca Traynor, Bryan Renton, Alan Moglia, Cristina Canosa, Antonio Ilardi, Antonio Cammarosano, Stefania Brunetti, Maura Ossola, Irene Restagno, Gabriella Chio, Adriano TI An ALS-FTD Patient Carrying a Double Pathogenetic Mutation of C9ORF72 and TARDBP: Case Report SO NEUROLOGY LA English DT Meeting Abstract CT 64th Annual Meeting of the American-Academy-of-Neurology (AAN) CY APR 21-28, 2012 CL New Orleans, LA SP Amer Acad Neurol (AAN) C1 [Calvo, Andrea; Moglia, Cristina; Canosa, Antonio; Ilardi, Antonio; Cammarosano, Stefania] Univ Turin, Turin, Italy. [Borghero, Giuseppe; Cannas, Antonino; Marrosu, Maria; Murru, Maria; Floris, Gianluca] Univ Cagliari, Cagliari, Italy. [Traynor, Bryan; Renton, Alan] NIH, Bethesda, MD 20892 USA. [Brunetti, Maura; Ossola, Irene; Restagno, Gabriella] OIRM S Anna, Turin, Italy. [Chio, Adriano] Univ Torino, Biella, Italy. NR 0 TC 0 Z9 0 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0028-3878 J9 NEUROLOGY JI Neurology PD APR PY 2012 VL 78 SU 1 MA IN91006 PG 3 WC Clinical Neurology SC Neurosciences & Neurology GA 931GQ UT WOS:000303204803068 ER PT J AU Calvo, A Borghero, G Cannas, A Marrosu, M Murru, M Floris, G Traynor, B Renton, A Moglia, C Canosa, A Ilardi, A Cammarosano, S Brunetti, M Ossola, I Restagno, G Chio, A AF Calvo, Andrea Borghero, Giuseppe Cannas, Antonino Marrosu, Maria Murru, Maria Floris, Gianluca Traynor, Bryan Renton, Alan Moglia, Cristina Canosa, Antonio Ilardi, Antonio Cammarosano, Stefania Brunetti, Maura Ossola, Irene Restagno, Gabriella Chio, Adriano TI An ALS-FTD Patient Carrying a Double Pathogenetic Mutation of C9ORF72 and TARDBP: Case Report SO NEUROLOGY LA English DT Meeting Abstract CT 64th Annual Meeting of the American-Academy-of-Neurology (AAN) CY APR 21-28, 2012 CL New Orleans, LA SP Amer Acad Neurol (AAN) C1 [Calvo, Andrea; Moglia, Cristina; Canosa, Antonio; Ilardi, Antonio; Cammarosano, Stefania] Univ Turin, Turin, Italy. [Borghero, Giuseppe; Cannas, Antonino; Marrosu, Maria; Murru, Maria; Floris, Gianluca] Univ Cagliari, Cagliari, Italy. [Traynor, Bryan; Renton, Alan] NIH, Bethesda, MD 20892 USA. [Brunetti, Maura; Ossola, Irene; Restagno, Gabriella] OIRM S Anna, Turin, Italy. [Chio, Adriano] Univ Torino, Biella, Italy. NR 0 TC 0 Z9 0 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0028-3878 J9 NEUROLOGY JI Neurology PD APR PY 2012 VL 78 SU 1 MA P01100 PG 2 WC Clinical Neurology SC Neurosciences & Neurology GA 931GQ UT WOS:000303204800143 ER PT J AU Chio, A Borghero, G Sabatelli, M Corbo, M Mora, G Giannini, F Conforti, F Penco, S Calvo, A Pugliatti, M Sotgiu, A Logroscino, G Traynor, B Renton, A Majounie, E Lauria, G Caponnetto, C Mandrioli, J Salvi, F Volanti, P La Bella, V Monsurro, M Zollino, M Ossola, I Brunetti, M Restagno, G AF Chio, Adriano Borghero, Giuseppe Sabatelli, Mario Corbo, Massimo Mora, Gabriele Giannini, Fabio Conforti, Francesca Penco, Silvana Calvo, Andrea Pugliatti, Maura Sotgiu, Alessandra Logroscino, Giancarlo Traynor, Bryan Renton, Alan Majounie, Elisa Lauria, Giuseppe Caponnetto, Claudia Mandrioli, Jessica Salvi, Fabrizio Volanti, Paolo La Bella, Vincenzo Monsurro, Maria Zollino, Marcella Ossola, Irene Brunetti, Maura Restagno, Gabriella TI C9ORF72 in a Large Series of Italian and Sardinian Familial and Sporadic ALS Patients SO NEUROLOGY LA English DT Meeting Abstract CT 64th Annual Meeting of the American-Academy-of-Neurology (AAN) CY APR 21-28, 2012 CL New Orleans, LA SP Amer Acad Neurol (AAN) C1 [Chio, Adriano; Calvo, Andrea; Ossola, Irene; Brunetti, Maura] Univ Turin, Turin, Italy. [Borghero, Giuseppe] Univ Cagliari, Cagliari, Italy. [Sabatelli, Mario] Univ Cattolica Sacro Cuore, Rome, Italy. [Corbo, Massimo] NEMO Ctr, Milan, Italy. [Mora, Gabriele] Fdn Maugeri, Milan, Italy. [Giannini, Fabio] Univ Siena, I-53100 Siena, Italy. [Conforti, Francesca] CNR, Cosenza, Italy. [Penco, Silvana] Osped Niguarda Ca Granda, Milan, Italy. [Pugliatti, Maura; Sotgiu, Alessandra] Univ Sassari, Milan, Italy. [Logroscino, Giancarlo] Univ Bari, Bari, Italy. [Traynor, Bryan; Renton, Alan; Majounie, Elisa] NIH, Bethesda, MD 20892 USA. [Lauria, Giuseppe] Ist Neurol Besta, Milan, Italy. [Caponnetto, Claudia] Univ Genoa, Genoa, Italy. [Mandrioli, Jessica] Univ Modena, I-41100 Modena, Italy. [Salvi, Fabrizio] Osped Bellaria, Cesena, FC, Italy. [Volanti, Paolo] Fdn Maugeri, Mistretta, Italy. [La Bella, Vincenzo] Univ Palermo, Palermo, Italy. [Monsurro, Maria] Univ Naples Federico II, Naples, Italy. [Zollino, Marcella] Catholic Hosp, Rome, Italy. [Restagno, Gabriella] OIRM SantAnna Hosp, Turin, Italy. RI La Bella, Vincenzo/H-4532-2012 NR 0 TC 0 Z9 0 U1 0 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 APR PY 2012 VL 78 SU 1 MA IN91003 PG 3 WC Clinical Neurology SC Neurosciences & Neurology GA 931GQ UT WOS:000303204803071 ER PT J AU Chio, A Restagno, G Brunetti, M Ossola, I Calvo, A Moglia, C Traynor, B Renton, A Majounie, E Corrado, L D'Alfonso, S Mora, G Mazzini, L AF Chio, Adriano Restagno, Gabriella Brunetti, Maura Ossola, Irene Calvo, Andrea Moglia, Cristina Traynor, Bryan Renton, Alan Majounie, Elisa Corrado, Lucia D'Alfonso, Sandra Mora, Gabriele Mazzini, Letizia CA PARALS Study Grp TI Genetics of ALS in Italy: A Population-Based Study SO NEUROLOGY LA English DT Meeting Abstract CT 64th Annual Meeting of the American-Academy-of-Neurology (AAN) CY APR 21-28, 2012 CL New Orleans, LA SP Amer Acad Neurol (AAN) C1 [Chio, Adriano] Unviers Torino, Biella, Italy. [Restagno, Gabriella; Brunetti, Maura; Ossola, Irene] ASO OIRM SantAnna, Turin, Italy. [Brunetti, Maura; Ossola, Irene] Dept Neurosci, Turin, Italy. [Calvo, Andrea; Moglia, Cristina] Univ Turin, Turin, Italy. [Traynor, Bryan; Renton, Alan; Majounie, Elisa] NIH, Bethesda, MD 20892 USA. [Corrado, Lucia; D'Alfonso, Sandra; Mazzini, Letizia] Univ Piemonte Orientale, Novara, Italy. [Mora, Gabriele] Fdn Maugeri, Milan, Italy. NR 0 TC 0 Z9 0 U1 0 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 APR PY 2012 VL 78 SU 1 MA IN91007 PG 2 WC Clinical Neurology SC Neurosciences & Neurology GA 931GQ UT WOS:000303204803067 ER PT J AU Chio, A Borghero, G Sabatelli, M Corbo, M Mora, G Giannini, F Conforti, F Penco, S Calvo, A Pugliatti, M Sotgiu, A Logroscino, G Traynor, B Renton, A Majounie, E Lauria, G Caponnetto, C Mandrioli, J Salvi, F Volanti, P La Bella, V Monsurro, M Zollino, M Ossola, I Brunetti, M Restagno, G AF Chio, Adriano Borghero, Giuseppe Sabatelli, Mario Corbo, Massimo Mora, Gabriele Giannini, Fabio Conforti, Francesca Penco, Silvana Calvo, Andrea Pugliatti, Maura Sotgiu, Alessandra Logroscino, Giancarlo Traynor, Bryan Renton, Alan Majounie, Elisa Lauria, Giuseppe Caponnetto, Claudia Mandrioli, Jessica Salvi, Fabrizio Volanti, Paolo La Bella, Vincenzo Monsurro, Maria Zollino, Marcella Ossola, Irene Brunetti, Maura Restagno, Gabriella TI C9ORF72 in a Large Series of Italian and Sardinian Familial and Sporadic ALS Patients SO NEUROLOGY LA English DT Meeting Abstract CT 64th Annual Meeting of the American-Academy-of-Neurology (AAN) CY APR 21-28, 2012 CL New Orleans, LA SP Amer Acad Neurol (AAN) C1 [Chio, Adriano; Calvo, Andrea; Ossola, Irene; Brunetti, Maura] Univ Turin, Turin, Italy. [Borghero, Giuseppe] Univ Cagliari, Cagliari, Italy. [Sabatelli, Mario] Univ Cattolica Sacro Cuore, Rome, Italy. [Corbo, Massimo] NEMO Ctr, Milan, Italy. [Mora, Gabriele] Fdn Maugeri, Milan, Italy. [Giannini, Fabio] Univ Siena, I-53100 Siena, Italy. [Conforti, Francesca] CNR Cosenza, Cosenza, Italy. [Penco, Silvana] Osped Niguarda Ca Granda, Milan, Italy. [Pugliatti, Maura] Univ Sassari, Milan, Italy. [Sotgiu, Alessandra] Univ Sassari, I-07100 Sassari, Italy. [Logroscino, Giancarlo] Univ Bari, Bari, Italy. [Traynor, Bryan; Renton, Alan; Majounie, Elisa] NIH, Bethesda, MD 20892 USA. [Lauria, Giuseppe] Ist Neurol Besta, Milan, Italy. [Caponnetto, Claudia] Univ Genoa, Genoa, Italy. [Mandrioli, Jessica] Univ Modena, I-41100 Modena, Italy. [Salvi, Fabrizio] Osped Bellaria, Cesena, FC, Italy. [Volanti, Paolo] Fdn Maugeri, Mistretta, Italy. [La Bella, Vincenzo] Univ Palermo, Palermo, Italy. [Monsurro, Maria] Univ Naples Federico II, Naples, Italy. [Zollino, Marcella] Catholic Hosp, Rome, Italy. [Restagno, Gabriella] OIRM St Anna Hosp, Turin, Italy. RI LOGROSCINO, GIANCARLO/K-5148-2016 OI LOGROSCINO, GIANCARLO/0000-0003-0423-3242 NR 0 TC 0 Z9 0 U1 0 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 APR PY 2012 VL 78 SU 1 MA P05161 PG 3 WC Clinical Neurology SC Neurosciences & Neurology GA 931GQ UT WOS:000303204802407 ER PT J AU Chio, A Restagno, G Brunetti, M Ossola, I Calvo, A Moglia, C Traynor, B Renton, A Majounie, E Corrado, L D'Alfonso, S Mora, G Mazzini, L AF Chio, Adriano Restagno, Gabriella Brunetti, Maura Ossola, Irene Calvo, Andrea Moglia, Cristina Traynor, Bryan Renton, Alan Majounie, Elisa Corrado, Lucia D'Alfonso, Sandra Mora, Gabriele Mazzini, Letizia CA PARALS Study Grp TI Genetics of ALS in Italy: A Population-Based Study SO NEUROLOGY LA English DT Meeting Abstract CT 64th Annual Meeting of the American-Academy-of-Neurology (AAN) CY APR 21-28, 2012 CL New Orleans, LA SP Amer Acad Neurol (AAN) C1 [Chio, Adriano] Univ Turin, Biella, Italy. [Restagno, Gabriella; Brunetti, Maura; Ossola, Irene] ASO OIRM St Anna, Turin, Italy. [Brunetti, Maura; Ossola, Irene] Dept Neurosci, Turin, Italy. [Calvo, Andrea; Moglia, Cristina] Univ Turin, Turin, Italy. [Traynor, Bryan; Renton, Alan; Majounie, Elisa] NIH, Bethesda, MD 20892 USA. [Corrado, Lucia; D'Alfonso, Sandra; Mazzini, Letizia] Univ Piemonte Orientale, Novara, Italy. [Mora, Gabriele] Fdn Maugeri, Milan, Italy. RI D'Alfonso, Sandra/K-7295-2014 OI D'Alfonso, Sandra/0000-0002-3983-9925 NR 0 TC 0 Z9 0 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0028-3878 J9 NEUROLOGY JI Neurology PD APR PY 2012 VL 78 SU 1 MA S05005 PG 2 WC Clinical Neurology SC Neurosciences & Neurology GA 931GQ UT WOS:000303204800412 ER PT J AU Czarnecki, K Kranick, S Horovitz, S Voon, V Ostuni, J Hallett, M AF Czarnecki, Kathrin Kranick, Sarah Horovitz, Silvina Voon, Valerie Ostuni, John Hallett, Mark TI Voxel-Based Morphometry (VBM) and Cortical Thickness in Motor Conversion Disorders SO NEUROLOGY LA English DT Meeting Abstract CT 64th Annual Meeting of the American-Academy-of-Neurology (AAN) CY APR 21-28, 2012 CL New Orleans, LA SP Amer Acad Neurol (AAN) C1 [Czarnecki, Kathrin] NINDS, Human Motor Control Sect, NIH, Bethesda, MD 20892 USA. [Kranick, Sarah] NINDS, NIH, Brookeville, MD USA. [Voon, Valerie] Behav & Clin Neurosci Inst, Dept Expt Psychol, Cambridge, England. NR 0 TC 0 Z9 0 U1 1 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0028-3878 J9 NEUROLOGY JI Neurology PD APR PY 2012 VL 78 SU 1 MA P03124 PG 2 WC Clinical Neurology SC Neurosciences & Neurology GA 931GQ UT WOS:000303204801480 ER PT J AU De Jesus-Acosta, C Rosado, N Hechavarria, R Miguel, LS Serrano, L Nath, A Wojna, V AF De Jesus-Acosta, Carolina Rosado, Noel Hechavarria, Rosa Miguel, Liza San Serrano, Luis Nath, Avindra Wojna, Valerie TI Thinning of Retinal Nerve Fiber Layer Is Associated with Neurocognitive Impairment in HIV Infected Women SO NEUROLOGY LA English DT Meeting Abstract CT 64th Annual Meeting of the American-Academy-of-Neurology (AAN) CY APR 21-28, 2012 CL New Orleans, LA SP Amer Acad Neurol (AAN) C1 [De Jesus-Acosta, Carolina] Duke Med Ctr Neuromuscular Med Fellowship, Durham, NC USA. [Rosado, Noel] Duke Med Ctr Cornea Fellowship, Duke Eye Ctr, Durham, NC USA. [Hechavarria, Rosa; Wojna, Valerie] Univ Puerto Rico, NeuroAIDS Program, San Juan, PR 00936 USA. [Miguel, Liza San; Wojna, Valerie] Univ Puerto Rico, Div Neurol, San Juan, PR 00936 USA. [Nath, Avindra] NINDS, Sect Infect Nervous Syst, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0028-3878 J9 NEUROLOGY JI Neurology PD APR PY 2012 VL 78 SU 1 MA P01263 PG 2 WC Clinical Neurology SC Neurosciences & Neurology GA 931GQ UT WOS:000303204800230 ER PT J AU Ellenstein, A Karabanov, A Song, SB Sigman, L Martinez, V Hallett, M AF Ellenstein, Aviva Karabanov, Anke Song, Sunbin Sigman, Lauren Martinez, Valeria Hallett, Mark TI Motor Sequence Learning Via the Mirror Neuron System SO NEUROLOGY LA English DT Meeting Abstract CT 64th Annual Meeting of the American-Academy-of-Neurology (AAN) CY APR 21-28, 2012 CL New Orleans, LA SP Amer Acad Neurol (AAN) C1 [Ellenstein, Aviva; Karabanov, Anke; Martinez, Valeria; Hallett, Mark] Natl Inst Neurol Disorders & Stroke, Human Motor Control Sect, NIH, Bethesda, MD USA. [Sigman, Lauren] Boston Univ, Sch Med, Boston, MA 02118 USA. [Song, Sunbin] Natl Inst Neurol Disorders & Stroke, Human Cort Physiol & Stroke Neurorehabil Unit, NIH, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 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 APR PY 2012 VL 78 SU 1 MA P04026 PG 2 WC Clinical Neurology SC Neurosciences & Neurology GA 931GQ UT WOS:000303204802229 ER PT J AU Gaitan, M de Alwis, M Sati, P Reich, D AF Gaitan, Maria de Alwis, Manori Sati, Pascal Reich, Daniel TI Multiple Sclerosis Changes the Size of Intralesional and Extralesional Parenchymal Veins SO NEUROLOGY LA English DT Meeting Abstract CT 64th Annual Meeting of the American-Academy-of-Neurology (AAN) CY APR 21-28, 2012 CL New Orleans, LA SP Amer Acad Neurol (AAN) C1 [Gaitan, Maria; Sati, Pascal; Reich, Daniel] NIH, Neuroimmunol Branch, Bethesda, MD 20892 USA. [de Alwis, Manori] Cornell Univ, New York, NY 10021 USA. RI Reich, Daniel/E-5701-2010 OI Reich, Daniel/0000-0002-2628-4334 NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0028-3878 J9 NEUROLOGY JI Neurology PD APR PY 2012 VL 78 SU 1 MA P03040 PG 2 WC Clinical Neurology SC Neurosciences & Neurology GA 931GQ UT WOS:000303204801516 ER PT J AU Gao, JJ Staub, H Zhao, EJ Chen, HL AF Gao, Jianjun Staub, Heidi Zhao, Edward J. Chen, Honglei TI Head Injury and Parkinson's Disease SO NEUROLOGY LA English DT Meeting Abstract CT 64th Annual Meeting of the American-Academy-of-Neurology (AAN) CY APR 21-28, 2012 CL New Orleans, LA SP Amer Acad Neurol (AAN) C1 [Gao, Jianjun; Zhao, Edward J.; Chen, Honglei] NIEHS, Epidemiol Branch, Res Triangle Pk, NC 27709 USA. [Staub, Heidi] Social & Sci Syst, Durham, NC USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0028-3878 J9 NEUROLOGY JI Neurology PD APR PY 2012 VL 78 SU 1 MA P07134 PG 1 WC Clinical Neurology SC Neurosciences & Neurology GA 931GQ UT WOS:000303204804153 ER PT J AU Gao, JJ Nalls, M Shi, M Joubert, B Hernandez, D Huang, XM Hollenbeck, A Singleton, A Chen, HL AF Gao, Jianjun Nalls, Michael Shi, Min Joubert, Bonnie Hernandez, Dena Huang, Xuemei Hollenbeck, Albert Singleton, Andrew Chen, Honglei TI An Exploratory Analysis on Gene-Environment Interactions for Parkinson Disease SO NEUROLOGY LA English DT Meeting Abstract CT 64th Annual Meeting of the American-Academy-of-Neurology (AAN) CY APR 21-28, 2012 CL New Orleans, LA SP Amer Acad Neurol (AAN) C1 [Gao, Jianjun; Joubert, Bonnie] NIEHS, Epidemiol Branch, Res Triangle Pk, NC 27709 USA. [Nalls, Michael; Hernandez, Dena; Singleton, Andrew] NIA, Neurogenet Lab, Bethesda, MD 20892 USA. [Shi, Min] NIEHS, Biostat Branch, Res Triangle Pk, NC 27709 USA. [Huang, Xuemei] Penn State Univ, Milton S Hershey Med Ctr, Dept Neurol, Hershey, PA 17033 USA. [Hollenbeck, Albert] AARP, Washington, DC USA. RI Singleton, Andrew/C-3010-2009 NR 0 TC 0 Z9 0 U1 1 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0028-3878 J9 NEUROLOGY JI Neurology PD APR PY 2012 VL 78 SU 1 MA PD4.003 PG 2 WC Clinical Neurology SC Neurosciences & Neurology GA 931GQ UT WOS:000303204802095 ER PT J AU Goldman, S Kamel, F Bhudhikanok, G Korell, M Meng, C Comyns, K Umbach, D Hoppin, J Ross, W Marras, C Kasten, M Chade, A Sandler, D Blair, A Langston, J Tanner, C AF Goldman, Samuel Kamel, Freya Bhudhikanok, Grace Korell, Monica Meng, Cheryl Comyns, Kathleen Umbach, David Hoppin, Jane Ross, Web Marras, Connie Kasten, Meike Chade, Anabel Sandler, Dale Blair, Aaron Langston, J. Tanner, Caroline TI Paraquat Use Modifies the Association of Head Injury and Parkinson's Disease SO NEUROLOGY LA English DT Meeting Abstract CT 64th Annual Meeting of the American-Academy-of-Neurology (AAN) CY APR 21-28, 2012 CL New Orleans, LA SP Amer Acad Neurol (AAN) C1 [Goldman, Samuel; Bhudhikanok, Grace; Korell, Monica; Meng, Cheryl; Comyns, Kathleen; Langston, J.] Parkinsons Inst, Sunnyvale, CA USA. [Umbach, David] NIEHS, Biostat Branch, Res Triangle Pk, NC 27709 USA. [Hoppin, Jane; Sandler, Dale] NIEHS, Epidemiol Branch, Res Triangle Pk, NC 27709 USA. [Ross, Web] Vet Affairs Pacific Isl Hlth Care Syst, Honolulu, HI USA. [Marras, Connie] Toronto Western Hosp, Toronto, ON M5T 2S8, Canada. [Kasten, Meike] Univ Lubeck, Lubeck, Germany. [Chade, Anabel] Favaloro Univ, Inst Neurosci, Buenos Aires, DF, Argentina. [Chade, Anabel] Favaloro Univ, Inst Cognit Neurol INECO, Buenos Aires, DF, Argentina. [Blair, Aaron] NCI, Occupat & Environm Epidemiol Branch, Div Canc Epidemiol & Genet, Rockville, MD USA. [Tanner, Caroline] TPI, Sunnyvale, CA USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0028-3878 J9 NEUROLOGY JI Neurology PD APR PY 2012 VL 78 SU 1 MA S42003 PG 3 WC Clinical Neurology SC Neurosciences & Neurology GA 931GQ UT WOS:000303204803105 ER PT J AU Gudmundsson, L Scher, A Aspelund, T Sigurdsson, S Vidal, JS Gudnason, V Launer, L AF Gudmundsson, Larus Scher, Ann Aspelund, Thor Sigurdsson, Sigurdur Vidal, Jean-Sebastien Gudnason, Vilmundur Launer, Lenore TI The Joint Association of Migraine and Depression with Brain Volume: The AGES-Reykjavik Study SO NEUROLOGY LA English DT Meeting Abstract CT 64th Annual Meeting of the American-Academy-of-Neurology (AAN) CY APR 21-28, 2012 CL New Orleans, LA SP Amer Acad Neurol (AAN) C1 [Gudmundsson, Larus; Scher, Ann] PMB Uniformed Serv Univ, Bethesda, MD USA. [Aspelund, Thor; Sigurdsson, Sigurdur; Gudnason, Vilmundur] Iceland Heart Assoc, Kopavogur, Iceland. [Vidal, Jean-Sebastien; Launer, Lenore] NIA, NIH, Bethesda, MD 20892 USA. RI Aspelund, Thor/C-5983-2008; Gudnason, Vilmundur/K-6885-2015 OI Aspelund, Thor/0000-0002-7998-5433; Gudnason, Vilmundur/0000-0001-5696-0084 NR 0 TC 0 Z9 0 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0028-3878 J9 NEUROLOGY JI Neurology PD APR PY 2012 VL 78 SU 1 MA S36003 PG 2 WC Clinical Neurology SC Neurosciences & Neurology GA 931GQ UT WOS:000303204802043 ER PT J AU Han, SP Salgado, A Alfahad, T Bielekova, B AF Han, Sungpil Salgado, Alan Alfahad, Tariq Bielekova, Bibiana TI Flow Cytometric Immunophenotyping of the Blood and CSF of Patients with Multiple Sclerosis SO NEUROLOGY LA English DT Meeting Abstract CT 64th Annual Meeting of the American-Academy-of-Neurology (AAN) CY APR 21-28, 2012 CL New Orleans, LA SP Amer Acad Neurol (AAN) C1 [Han, Sungpil; Salgado, Alan; Bielekova, Bibiana] NIH, Neuroimmunol Branch, Bethesda, MD 20892 USA. [Alfahad, Tariq] NIH, Neuroimmunol Branch, Arlington, VA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0028-3878 J9 NEUROLOGY JI Neurology PD APR PY 2012 VL 78 SU 1 MA P02.081 PG 2 WC Clinical Neurology SC Neurosciences & Neurology GA 931GQ UT WOS:000303204801211 ER PT J AU Harrison, D Oh, J Jones, C Hua, J Wood, E Calabresi, P Van Zijl, P Reich, D AF Harrison, Daniel Oh, Jiwon Jones, Craig Hua, Jun Wood, Emily Calabresi, Peter Van Zijl, Peter Reich, Daniel TI A Method for Analysis of Cortical Lesions on 7-Tesla MRI in Multiple Sclerosis SO NEUROLOGY LA English DT Meeting Abstract CT 64th Annual Meeting of the American-Academy-of-Neurology (AAN) CY APR 21-28, 2012 CL New Orleans, LA SP Amer Acad Neurol (AAN) C1 [Harrison, Daniel; Oh, Jiwon; Wood, Emily; Calabresi, Peter] Johns Hopkins Univ, Sch Med, Baltimore, MD USA. [Hua, Jun] Kennedy Krieger Inst, FM Kirby Res Ctr, Dept Radiol, Baltimore, MD USA. [Reich, Daniel] Natl Inst Neurol Disorders & Stroke, Neuroimmunol Branch, Bethesda, MD USA. RI Hua, Jun/F-7879-2012; Reich, Daniel/E-5701-2010 OI Reich, Daniel/0000-0002-2628-4334 NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0028-3878 J9 NEUROLOGY JI Neurology PD APR PY 2012 VL 78 SU 1 MA P03064 PG 2 WC Clinical Neurology SC Neurosciences & Neurology GA 931GQ UT WOS:000303204801531 ER PT J AU Herman, M Wu, TX Bielekova, B AF Herman, Matthew Wu, Tianxia Bielekova, Bibiana TI Cerebrospinal Fluid IL-12p40 Is a Biomarker of Intrathecal Inflammation in Multiple Sclerosis SO NEUROLOGY LA English DT Meeting Abstract CT 64th Annual Meeting of the American-Academy-of-Neurology (AAN) CY APR 21-28, 2012 CL New Orleans, LA SP Amer Acad Neurol (AAN) C1 [Herman, Matthew; Wu, Tianxia; Bielekova, Bibiana] NINDS, Neuroimmunol Branch, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0028-3878 J9 NEUROLOGY JI Neurology PD APR PY 2012 VL 78 SU 1 MA S40006 PG 1 WC Clinical Neurology SC Neurosciences & Neurology GA 931GQ UT WOS:000303204802063 ER PT J AU Hernandez, D Merino, J Freeman, J Luby, M Warach, S Latour, L AF Hernandez, Daymara Merino, Jose Freeman, Jason Luby, Marie Warach, Steven Latour, Lawrence TI Gradient-Echo and Segmented-EPI Imaging Comparison in Thrombolytic Treated Patients SO NEUROLOGY LA English DT Meeting Abstract CT 64th Annual Meeting of the American-Academy-of-Neurology (AAN) CY APR 21-28, 2012 CL New Orleans, LA SP Amer Acad Neurol (AAN) C1 [Hernandez, Daymara; Merino, Jose; Freeman, Jason; Luby, Marie; Warach, Steven; Latour, Lawrence] NINDS, Sect Stroke Diagnost & Therapeut, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0028-3878 J9 NEUROLOGY JI Neurology PD APR PY 2012 VL 78 SU 1 MA S23003 PG 2 WC Clinical Neurology SC Neurosciences & Neurology GA 931GQ UT WOS:000303204801552 ER PT J AU Hernandez, D Merino, J Freeman, J Luby, M Warach, S Latour, L AF Hernandez, Daymara Merino, Jose Freeman, Jason Luby, Marie Warach, Steven Latour, Lawrence TI Gradient-Echo and Segmented-EPI Imaging Comparison in Thrombolytic Treated Patients SO NEUROLOGY LA English DT Meeting Abstract CT 64th Annual Meeting of the American-Academy-of-Neurology (AAN) CY APR 21-28, 2012 CL New Orleans, LA SP Amer Acad Neurol (AAN) C1 [Hernandez, Daymara; Merino, Jose; Freeman, Jason; Luby, Marie; Warach, Steven; Latour, Lawrence] Natl Inst Neurol Disorders & Stroke, Sect Stroke Diagnost & Therapeut, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0028-3878 J9 NEUROLOGY JI Neurology PD APR PY 2012 VL 78 SU 1 MA IN21004 PG 2 WC Clinical Neurology SC Neurosciences & Neurology GA 931GQ UT WOS:000303204800028 ER PT J AU Kamel, F Richardson, G Umbach, D Richards, M Bhudhikanok, G Blair, A Chade, A Comyns, K Goldman, S Hoppin, J Kasten, M Korell, M Marras, C Meng, C Ross, G Langston, J Sandler, D Tanner, C AF Kamel, Freya Richardson, Gina Umbach, David Richards, Marie Bhudhikanok, Grace Blair, Aaron Chade, Anabel Comyns, Kathleen Goldman, Samuel Hoppin, Jane Kasten, Meike Korell, Monica Marras, Connie Meng, Cheryl Ross, G. Langston, J. Sandler, Dale Tanner, Caroline TI Risk of Parkinson's Disease (PD) Associated with the Herbicide Paraquat Is Attenuated by High Dietary Intake of Polyunsaturated Fatty Acids (PUFAs) SO NEUROLOGY LA English DT Meeting Abstract CT 64th Annual Meeting of the American-Academy-of-Neurology (AAN) CY APR 21-28, 2012 CL New Orleans, LA SP Amer Acad Neurol (AAN) C1 [Kamel, Freya; Richardson, Gina; Umbach, David; Hoppin, Jane; Sandler, Dale] NIEHS, Res Triangle Pk, NC 27709 USA. [Richards, Marie] Westat Corp, Durham, NC USA. [Bhudhikanok, Grace; Comyns, Kathleen; Goldman, Samuel; Korell, Monica; Meng, Cheryl; Langston, J.; Tanner, Caroline] Parkinsons Inst, Sunnyvale, CA USA. [Blair, Aaron] NCI, Rockville, MD USA. [Chade, Anabel] Favaloro Univ, Buenos Aires, DF, Argentina. [Kasten, Meike] Univ Lubeck, Lubeck, Germany. [Marras, Connie] Univ Toronto, Toronto, ON, Canada. [Ross, G.] VA Pacific Isl Hlth Care Syst, Honolulu, HI USA. NR 0 TC 0 Z9 0 U1 1 U2 5 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0028-3878 J9 NEUROLOGY JI Neurology PD APR PY 2012 VL 78 SU 1 MA S42004 PG 2 WC Clinical Neurology SC Neurosciences & Neurology GA 931GQ UT WOS:000303204803106 ER PT J AU Kapogiannis, D Reiter, D AF Kapogiannis, Dimitrios Reiter, David TI Precuneus Glutamate and GABA Predict Default Mode Network Activity SO NEUROLOGY LA English DT Meeting Abstract CT 64th Annual Meeting of the American-Academy-of-Neurology (AAN) CY APR 21-28, 2012 CL New Orleans, LA SP Amer Acad Neurol (AAN) C1 [Kapogiannis, Dimitrios; Reiter, David] NIA, Clin Res Branch, NIH, Baltimore, MD 21224 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0028-3878 J9 NEUROLOGY JI Neurology PD APR PY 2012 VL 78 SU 1 MA PD7005 PG 2 WC Clinical Neurology SC Neurosciences & Neurology GA 931GQ UT WOS:000303204803233 ER PT J AU Kapogiannis, D Reiter, D AF Kapogiannis, Dimitrios Reiter, David TI Precuneus Glutamate and GABA Predict Default Mode Network Activity SO NEUROLOGY LA English DT Meeting Abstract CT 64th Annual Meeting of the American-Academy-of-Neurology (AAN) CY APR 21-28, 2012 CL New Orleans, LA SP Amer Acad Neurol (AAN) C1 [Kapogiannis, Dimitrios; Reiter, David] NIA, Clin Res Branch, NIH, Baltimore, MD 21224 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0028-3878 J9 NEUROLOGY JI Neurology PD APR PY 2012 VL 78 SU 1 MA IN41001 PG 1 WC Clinical Neurology SC Neurosciences & Neurology GA 931GQ UT WOS:000303204800082 ER PT J AU Kranick, S Holland, S Uzel, G Nath, A AF Kranick, Sarah Holland, Steven Uzel, Gulbu Nath, Avindra TI CNS Complications in Immunodeficiency Syndromes Due to Mutations in Transcription Factors STAT-1 and GATA-2 SO NEUROLOGY LA English DT Meeting Abstract CT 64th Annual Meeting of the American-Academy-of-Neurology (AAN) CY APR 21-28, 2012 CL New Orleans, LA SP Amer Acad Neurol (AAN) C1 [Kranick, Sarah] Natl Inst Neurol Disorders & Stroke, Neurol Consult Serv, NIH, Bethesda, MD USA. [Holland, Steven; Uzel, Gulbu] NIAID, Lab Clin Infect Dis, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0028-3878 J9 NEUROLOGY JI Neurology PD APR PY 2012 VL 78 SU 1 MA S57003 PG 2 WC Clinical Neurology SC Neurosciences & Neurology GA 931GQ UT WOS:000303204803197 ER PT J AU Kreisl, W Brown, A Lyoo, CH Zhang, Y Morse, C Jenko, K Clark, D Zoghbi, S Esposito, D Mbeo, G Creighton, J Pike, V Innis, R McArthur, J AF Kreisl, William Brown, Amira Lyoo, Chul Hyoung Zhang, Yi Morse, Cheryl Jenko, Kimberly Clark, David Zoghbi, Sami Esposito, Deneen Mbeo, Gilbert Creighton, Jason Pike, Victor Innis, Robert McArthur, Justin TI Mild Neurocognitive Impairment in HIV Infection Is Associated with Neuroinflammation on Positron Emission Tomography SO NEUROLOGY LA English DT Meeting Abstract CT 64th Annual Meeting of the American-Academy-of-Neurology (AAN) CY APR 21-28, 2012 CL New Orleans, LA SP Amer Acad Neurol (AAN) C1 [Kreisl, William; Brown, Amira; Lyoo, Chul Hyoung; Zhang, Yi; Morse, Cheryl; Jenko, Kimberly; Clark, David; Zoghbi, Sami; Pike, Victor; Innis, Robert] NIMH, Bethesda, MD 20892 USA. [Esposito, Deneen; Mbeo, Gilbert; Creighton, Jason; McArthur, Justin] Johns Hopkins Univ, Baltimore, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0028-3878 J9 NEUROLOGY JI Neurology PD APR PY 2012 VL 78 SU 1 MA S37003 PG 3 WC Clinical Neurology SC Neurosciences & Neurology GA 931GQ UT WOS:000303204802072 ER PT J AU Kreisl, W Brown, A Lyoo, CH Zhang, Y Morse, C Jenko, K Clark, D Zoghbi, S Esposito, D Mbeo, G Creighton, J Pike, V Innis, R McArthur, J AF Kreisl, William Brown, Amira Lyoo, Chul Hyoung Zhang, Yi Morse, Cheryl Jenko, Kimberly Clark, David Zoghbi, Sami Esposito, Deneen Mbeo, Gilbert Creighton, Jason Pike, Victor Innis, Robert McArthur, Justin TI Mild Neurocognitive Impairment in HIV Infection Is Associated with Neuroinflammation on Positron Emission Tomography SO NEUROLOGY LA English DT Meeting Abstract CT 64th Annual Meeting of the American-Academy-of-Neurology (AAN) CY APR 21-28, 2012 CL New Orleans, LA SP Amer Acad Neurol (AAN) C1 [Kreisl, William; Brown, Amira; Lyoo, Chul Hyoung; Zhang, Yi; Morse, Cheryl; Jenko, Kimberly; Clark, David; Zoghbi, Sami; Pike, Victor; Innis, Robert] NIMH, Bethesda, MD 20892 USA. [Esposito, Deneen; Mbeo, Gilbert; Creighton, Jason; McArthur, Justin] Johns Hopkins Univ, Baltimore, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0028-3878 J9 NEUROLOGY JI Neurology PD APR PY 2012 VL 78 SU 1 MA IN31008 PG 2 WC Clinical Neurology SC Neurosciences & Neurology GA 931GQ UT WOS:000303204800069 ER PT J AU Lee, P Xu, QG Herman, M Reich, D Bielekova, B AF Lee, Paul Xu, Quangang Herman, Matthew Reich, Daniel Bielekova, Bibiana TI Distinct Phenotype of Immortalized CSF B-Cells in Multiple Sclerosis SO NEUROLOGY LA English DT Meeting Abstract CT 64th Annual Meeting of the American-Academy-of-Neurology (AAN) CY APR 21-28, 2012 CL New Orleans, LA SP Amer Acad Neurol (AAN) C1 [Herman, Matthew] NIH, Neuroimmunol Branch, Bethesda, MD 20892 USA. [Xu, Quangang] Chinese Peoples Liberat Army Gen Hosp, Beijing, Peoples R China. RI Reich, Daniel/E-5701-2010 OI Reich, Daniel/0000-0002-2628-4334 NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0028-3878 J9 NEUROLOGY JI Neurology PD APR PY 2012 VL 78 SU 1 MA S30007 PG 2 WC Clinical Neurology SC Neurosciences & Neurology GA 931GQ UT WOS:000303204802027 ER PT J AU Leishear, K Boudreau, R Studenski, S Ferrucci, L Rosano, C de Rekeneire, N Houston, D Kritchevsky, S Schwartz, A Vinik, A Hogervorst, E Yaffe, K Harris, T Newman, A Strotmeyer, E AF Leishear, Kira Boudreau, Robert Studenski, Stephanie Ferrucci, Luigi Rosano, Caterina de Rekeneire, Nathalie Houston, Denise Kritchevsky, Stephen Schwartz, Ann Vinik, Aaron Hogervorst, Eva Yaffe, Kristine Harris, Tamara Newman, Anne Strotmeyer, Elsa TI Vitamin B12 and Neurological Function: Is There a Threshold Level? SO NEUROLOGY LA English DT Meeting Abstract CT 64th Annual Meeting of the American-Academy-of-Neurology (AAN) CY APR 21-28, 2012 CL New Orleans, LA SP Amer Acad Neurol (AAN) C1 [Leishear, Kira; Boudreau, Robert; Studenski, Stephanie; Rosano, Caterina; Newman, Anne; Strotmeyer, Elsa] Univ Pittsburgh, Pittsburgh, PA USA. [Ferrucci, Luigi] NIA, Baltimore, MD 21224 USA. [de Rekeneire, Nathalie] Yale Univ, Sch Med, New Haven, CT USA. [Houston, Denise; Kritchevsky, Stephen] Wake Forest Sch Med, Winston Salem, NC USA. [Schwartz, Ann; Yaffe, Kristine] UCSF, San Francisco, CA USA. [Vinik, Aaron] EVMS Strelitz Diabet Res Ctr, Norfolk, VA USA. [Hogervorst, Eva] Univ Loughborough, Loughborough, Leics, England. [Harris, Tamara] NIA, Bethesda, MD 20892 USA. RI Newman, Anne/C-6408-2013; Strotmeyer, Elsa/F-3015-2014 OI Newman, Anne/0000-0002-0106-1150; NR 0 TC 0 Z9 0 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0028-3878 J9 NEUROLOGY JI Neurology PD APR PY 2012 VL 78 SU 1 MA P02059 PG 3 WC Clinical Neurology SC Neurosciences & Neurology GA 931GQ UT WOS:000303204801006 ER PT J AU Lewis, J Wassermann, E AF Lewis, Jeffrey Wassermann, Eric TI Anhedonia in Combat Veterans with Penetrating Head Injury SO NEUROLOGY LA English DT Meeting Abstract CT 64th Annual Meeting of the American-Academy-of-Neurology (AAN) CY APR 21-28, 2012 CL New Orleans, LA SP Amer Acad Neurol (AAN) C1 [Lewis, Jeffrey; Wassermann, Eric] NINDS, Behav Neurol Unit, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0028-3878 J9 NEUROLOGY JI Neurology PD APR PY 2012 VL 78 SU 1 MA P01180 PG 1 WC Clinical Neurology SC Neurosciences & Neurology GA 931GQ UT WOS:000303204800260 ER PT J AU Lewis, J Wassermann, E AF Lewis, Jeffrey Wassermann, Eric TI Anhedonia in Combat Veterans with Penetrating Head Injury SO NEUROLOGY LA English DT Meeting Abstract CT 64th Annual Meeting of the American-Academy-of-Neurology (AAN) CY APR 21-28, 2012 CL New Orleans, LA SP Amer Acad Neurol (AAN) C1 [Lewis, Jeffrey; Wassermann, Eric] NINDS, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0028-3878 J9 NEUROLOGY JI Neurology PD APR PY 2012 VL 78 SU 1 MA IN41009 PG 2 WC Clinical Neurology SC Neurosciences & Neurology GA 931GQ UT WOS:000303204800090 ER PT J AU Lill, C Meissner, E Schjeide, L Schjeide, BM Liebsch, M Roehr, J Rouleau, G Hardiman, O Traynor, B Van den Berg, L Al-Chalabi, A Bertram, L AF Lill, Christina Meissner, Esther Schjeide, Leif Schjeide, Brit-Maren Liebsch, Maria Roehr, Johannes Rouleau, Guy Hardiman, Orla Traynor, Bryan Van den Berg, Leonard Al-Chalabi, Ammar Bertram, Lars TI Comprehensive Research Synopsis and Systematic Meta-Analyses in ALS Genetics: The ALSGene Database SO NEUROLOGY LA English DT Meeting Abstract CT 64th Annual Meeting of the American-Academy-of-Neurology (AAN) CY APR 21-28, 2012 CL New Orleans, LA SP Amer Acad Neurol (AAN) C1 [Lill, Christina; Meissner, Esther; Schjeide, Leif; Schjeide, Brit-Maren; Liebsch, Maria; Roehr, Johannes; Bertram, Lars] Max Planck Inst Mol Genet, Dept Vertebrate Genom, D-14195 Berlin, Germany. [Rouleau, Guy] CHUM Res Ctr, Montreal, PQ, Canada. [Hardiman, Orla] Trinity Coll Dublin, Dublin, Ireland. [Hardiman, Orla] Beaumont Hosp, Dublin 9, Ireland. [Traynor, Bryan] NIA, Bethesda, MD 20892 USA. [Van den Berg, Leonard] Univ Utrecht, Rudolf Magnus Inst, Utrecht, Netherlands. [Al-Chalabi, Ammar] Kings Coll London, London WC2R 2LS, England. RI Al-Chalabi, Ammar/E-5361-2010 OI Al-Chalabi, Ammar/0000-0002-4924-7712 NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0028-3878 J9 NEUROLOGY JI Neurology PD APR PY 2012 VL 78 SU 1 MA P01095 PG 3 WC Clinical Neurology SC Neurosciences & Neurology GA 931GQ UT WOS:000303204800148 ER PT J AU Lublin, F Cofield, S Cutter, G Conwit, R Narayana, P Nelson, F Gustafson, T Wolinsky, J AF Lublin, Fred Cofield, Stacey Cutter, Gary Conwit, Robin Narayana, Ponnada Nelson, Flavia Gustafson, Tarah Wolinsky, Jerry CA CombiRx Investigators TI The CombiRx Trial: A Multi-Center, Double-Blind, Randomized Study Comparing the Combined Use of Interferon Beta-1a and Glatiramer Acetate to Either Agent Alone in Participants with Relapsing-Remitting Multiple Sclerosis - Clinical Outcomes SO NEUROLOGY LA English DT Meeting Abstract CT 64th Annual Meeting of the American-Academy-of-Neurology (AAN) CY APR 21-28, 2012 CL New Orleans, LA SP Amer Acad Neurol (AAN) C1 [Lublin, Fred; Gustafson, Tarah; CombiRx Investigators] Mt Sinai Sch Med, New York, NY USA. [Cofield, Stacey; Cutter, Gary] Univ Alabama Birmingham, Birmingham, AL USA. [Conwit, Robin] NINDS, NIH, Lutherville Timonium, MD USA. [Narayana, Ponnada; Nelson, Flavia; Wolinsky, Jerry] Univ Texas Hlth Sci Ctr Houston, Houston, TX USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0028-3878 J9 NEUROLOGY JI Neurology PD APR PY 2012 VL 78 SU 1 MA PL02003 PG 3 WC Clinical Neurology SC Neurosciences & Neurology GA 931GQ UT WOS:000303204804243 ER PT J AU Masdeu, J Mattay, V Chen, Q Kohn, P Muse, J Kolachana, B Nichols, L Weinberger, D Berman, K AF Masdeu, Joseph Mattay, Venkata Chen, Qiang Kohn, Philip Muse, John Kolachana, Bhaskar Nichols, Lisa Weinberger, Daniel Berman, Karen TI Age-Related Effect of APOE Genotype on Brain Functional Connectivity during Episodic Memory Encoding SO NEUROLOGY LA English DT Meeting Abstract CT 64th Annual Meeting of the American-Academy-of-Neurology (AAN) CY APR 21-28, 2012 CL New Orleans, LA SP Amer Acad Neurol (AAN) C1 [Masdeu, Joseph; Chen, Qiang; Kohn, Philip; Muse, John; Kolachana, Bhaskar; Nichols, Lisa; Weinberger, Daniel; Berman, Karen] NIH, Bethesda, MD 20892 USA. [Mattay, Venkata] Intramural Natl Inst Hlth, Mclean, VA USA. NR 0 TC 0 Z9 0 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 APR PY 2012 VL 78 SU 1 MA P03084 PG 2 WC Clinical Neurology SC Neurosciences & Neurology GA 931GQ UT WOS:000303204801300 ER PT J AU Nair, G Inati, S Kranick, S Quezado, M Sereti, I Sheikh, V Reich, D Nath, A AF Nair, Govind Inati, Souheil Kranick, Sarah Quezado, Martha Sereti, Irini Sheikh, Virginia Reich, Daniel Nath, Avindra TI Postmortem MRI in Progressive Multifocal Leukoencephalopathy SO NEUROLOGY LA English DT Meeting Abstract CT 64th Annual Meeting of the American-Academy-of-Neurology (AAN) CY APR 21-28, 2012 CL New Orleans, LA SP Amer Acad Neurol (AAN) C1 [Nair, Govind; Reich, Daniel] NINDS, NIH, Bethesda, MD 20892 USA. [Inati, Souheil] NIMH, NIH, Bethesda, MD 20892 USA. [Kranick, Sarah] NIH, Brookeville, MD USA. [Quezado, Martha] NCI, NIH, Bethesda, MD 20892 USA. [Sereti, Irini; Sheikh, Virginia] NIAID, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0028-3878 J9 NEUROLOGY JI Neurology PD APR PY 2012 VL 78 SU 1 MA P02272 PG 3 WC Clinical Neurology SC Neurosciences & Neurology GA 931GQ UT WOS:000303204801104 ER PT J AU Nath, A Choi, E Wang, TG AF Nath, Avindra Choi, Elliot Wang, Tongguang TI Direct Conversion to Neurons from Adult Human Fibroblasts and Hematopoietic Stem Cells In Vitro SO NEUROLOGY LA English DT Meeting Abstract CT 64th Annual Meeting of the American-Academy-of-Neurology (AAN) CY APR 21-28, 2012 CL New Orleans, LA SP Amer Acad Neurol (AAN) C1 [Nath, Avindra; Choi, Elliot; Wang, Tongguang] NINDS, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0028-3878 J9 NEUROLOGY JI Neurology PD APR PY 2012 VL 78 SU 1 MA IN81003 PG 1 WC Clinical Neurology SC Neurosciences & Neurology GA 931GQ UT WOS:000303204801542 ER PT J AU Nath, A Choi, E Wang, TG AF Nath, Avindra Choi, Elliot Wang, Tongguang TI Direct Conversion to Neurons from Adult Human Fibroblasts and Hematopoietic Stem Cells In Vitro SO NEUROLOGY LA English DT Meeting Abstract CT 64th Annual Meeting of the American-Academy-of-Neurology (AAN) CY APR 21-28, 2012 CL New Orleans, LA SP Amer Acad Neurol (AAN) C1 [Nath, Avindra; Choi, Elliot; Wang, Tongguang] NINDS, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0028-3878 J9 NEUROLOGY JI Neurology PD APR PY 2012 VL 78 SU 1 MA P02014 PG 2 WC Clinical Neurology SC Neurosciences & Neurology GA 931GQ UT WOS:000303204801135 ER PT J AU Nath, A Major, E Aksamit, A Calabrese, L Sejvar, J Kotton, C Barhams, M AF Nath, Avindra Major, Eugene Aksamit, Allen Calabrese, Leonard Sejvar, James Kotton, Camille Barhams, Maria TI Establishment of a Registry To Identify Cases of PML Using Uniform Diagnostic Criteria SO NEUROLOGY LA English DT Meeting Abstract CT 64th Annual Meeting of the American-Academy-of-Neurology (AAN) CY APR 21-28, 2012 CL New Orleans, LA SP Amer Acad Neurol (AAN) C1 [Nath, Avindra; Major, Eugene; Barhams, Maria] NINDS, NIH, Bethesda, MD 20892 USA. [Aksamit, Allen] Mayo Clin, Rochester, MN USA. [Calabrese, Leonard] Cleveland Clin, Cleveland, OH 44106 USA. [Sejvar, James] CDC, Decatur, GA USA. [Kotton, Camille] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0028-3878 J9 NEUROLOGY JI Neurology PD APR PY 2012 VL 78 SU 1 MA S08002 PG 2 WC Clinical Neurology SC Neurosciences & Neurology GA 931GQ UT WOS:000303204800420 ER PT J AU Nayak, L Scott, J Bauchet, L Fraum, T Cooper, A Chao, S Suh, J Abrey, L Peereboom, D Zouaoui, S Fabbro-Peray, P Taillandier, L Rigao, V Vogelbaum, M Mathieu-Daude, H DeAngelis, L Shih, J Iwamoto, F AF Nayak, Lakshmi Scott, Jacob Bauchet, Luc Fraum, Tyler Cooper, Anna Chao, Samuel Suh, John Abrey, Lauren Peereboom, David Zouaoui, Sonia Fabbro-Peray, Pascale Taillandier, Luc Rigao, Valerie Vogelbaum, Michael Mathieu-Daude, Helene DeAngelis, Lisa Shih, Joanna Iwamoto, Fabio TI Recursive Partitioning Analysis Identifies Prognostic Groups for Glioblastoma Patients Aged 70 Years or Older SO NEUROLOGY LA English DT Meeting Abstract CT 64th Annual Meeting of the American-Academy-of-Neurology (AAN) CY APR 21-28, 2012 CL New Orleans, LA SP Amer Acad Neurol (AAN) C1 [Nayak, Lakshmi] Dana Farber Canc Inst, Ctr Neurooncol, Boston, MA 02115 USA. [Scott, Jacob] Univ S Florida, H Lee Moffitt Canc Ctr, Dept Radiat Oncol, Tampa, FL 33682 USA. [Bauchet, Luc; Zouaoui, Sonia] Hop St Eloi Gui de Chauliac, Dept Neurosurg, Montpellier, France. [Bauchet, Luc; Zouaoui, Sonia] Hop St Eloi Gui de Chauliac, INSERM, U583, Montpellier, France. [Fraum, Tyler] Duke Univ, Sch Med, Durham, NC USA. [Cooper, Anna] Univ Rochester, Sch Med & Dent, Rochester, NY USA. [Vogelbaum, Michael] Cleveland Clin Fdn, Brain Tumor & Neurooncol Ctr, Cleveland, OH 44195 USA. [Abrey, Lauren] F Hoffmann La Roche Ltd, Basel, Switzerland. [Fabbro-Peray, Pascale] Inst Univ Rech Clin, Montpellier, France. [Taillandier, Luc] Hop Neurol, Nancy, France. [Rigao, Valerie] Hop Gui de Chauliac, Dept Pathl, Ctr Hosp Univ, Montpellier, France. [Mathieu-Daude, Helene] Languedoc Roussillon Registre Tumeurs Herault, Grp Neurooncol, Montpellier, France. [DeAngelis, Lisa] Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. [Shih, Joanna] NCI, Biometr Res Branch, Div Canc Treatment & Diag, NIH, Rockville, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0028-3878 J9 NEUROLOGY JI Neurology PD APR PY 2012 VL 78 SU 1 MA P07109 PG 2 WC Clinical Neurology SC Neurosciences & Neurology GA 931GQ UT WOS:000303204804095 ER PT J AU Oh, J Zackowski, K Chen, M Newsome, S Smith, S Prince, J Calabresi, P Reich, D AF Oh, Jiwon Zackowski, Kathleen Chen, Min Newsome, Scott Smith, Seth Prince, Jerry Calabresi, Peter Reich, Daniel TI Diffusion Tensor and Magnetization Transfer Imaging Correlates of Motor Dysfunction in the Spinal Cord in Multiple Sclerosis SO NEUROLOGY LA English DT Meeting Abstract CT 64th Annual Meeting of the American-Academy-of-Neurology (AAN) CY APR 21-28, 2012 CL New Orleans, LA SP Amer Acad Neurol (AAN) C1 [Oh, Jiwon] Johsn Hopkins Univ, Baltimore, MD USA. [Zackowski, Kathleen] Johns Hopkins Univ, Kennedy Krieger Inst, Baltimore, MD USA. [Newsome, Scott] Johns Hopkins Univ, Abingdon, MD USA. [Smith, Seth] Vanderbilt Univ, Nashville, TN USA. [Reich, Daniel] NINDS, Translat Neuroradiol Unit, Bethesda, MD 20892 USA. RI Reich, Daniel/E-5701-2010 OI Reich, Daniel/0000-0002-2628-4334 NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0028-3878 J9 NEUROLOGY JI Neurology PD APR PY 2012 VL 78 SU 1 MA S21002 PG 2 WC Clinical Neurology SC Neurosciences & Neurology GA 931GQ UT WOS:000303204801568 ER PT J AU Rinaldi, C Grunseich, C Sevrioukova, I Schindler, A Ghezzi, D Zeviani, M Fischbeck, K AF Rinaldi, Carlo Grunseich, Christopher Sevrioukova, Irina Schindler, Alice Ghezzi, Daniele Zeviani, Massimo Fischbeck, Kenneth TI X-Linked Recessive Axonal Neuropathy with Deafness and Cognitive Impairment (Cowchock Syndrome) Is Associated with Mutation in AIFM1 SO NEUROLOGY LA English DT Meeting Abstract CT 64th Annual Meeting of the American-Academy-of-Neurology (AAN) CY APR 21-28, 2012 CL New Orleans, LA SP Amer Acad Neurol (AAN) C1 [Rinaldi, Carlo; Grunseich, Christopher; Schindler, Alice; Fischbeck, Kenneth] NINDS, Neurogenet Branch, Bethesda, MD 20892 USA. [Sevrioukova, Irina] Univ Calif Irvine, Irvine, CA USA. [Ghezzi, Daniele; Zeviani, Massimo] Natl Neurol Inst Carlo Besta, Unit Mol Neurogenet, Milan, Italy. RI Ghezzi, Daniele/J-7873-2016 NR 0 TC 0 Z9 0 U1 0 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 APR PY 2012 VL 78 SU 1 MA S07007 PG 2 WC Clinical Neurology SC Neurosciences & Neurology GA 931GQ UT WOS:000303204800422 ER PT J AU Ross, W Duda, J Abbott, R Petrovitch, H Tanner, C Masaki, K Uyehara-Lock, J Launer, L White, L AF Ross, Web Duda, John Abbott, Robert Petrovitch, Helen Tanner, Caroline Masaki, Kamal Uyehara-Lock, Jane Launer, Lenore White, Lon TI Association of Coffee and Caffeine Consumption with Brain Lewy Pathology in the Honolulu-Asia Aging Study SO NEUROLOGY LA English DT Meeting Abstract CT 64th Annual Meeting of the American-Academy-of-Neurology (AAN) CY APR 21-28, 2012 CL New Orleans, LA SP Amer Acad Neurol (AAN) C1 [Ross, Web] VA Pacific Isl Hlth Care Syst, Honolulu, HI USA. [Duda, John] Philadelphia VA Med Ctr, Philadelphia, PA USA. [Abbott, Robert] Univ Virginia, Sch Med, Charlottesville, VA 22908 USA. [Petrovitch, Helen] Pacific Hlth Res & Educ Inst, Kailua, HI USA. [Tanner, Caroline] Parkinsons Inst, Sunnyvale, CA USA. [Masaki, Kamal] Univ Hawaii, John A Burns Sch Med, Honolulu, HI 96822 USA. [Launer, Lenore] NIA, NIH, Washington, DC USA. [White, Lon] Kuakini Med Ctr, Honolulu, HI USA. [Uyehara-Lock, Jane] U Hawaii John A Burns Sch Med, Honolulu, HI USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0028-3878 J9 NEUROLOGY JI Neurology PD APR PY 2012 VL 78 SU 1 MA S42005 PG 2 WC Clinical Neurology SC Neurosciences & Neurology GA 931GQ UT WOS:000303204803107 ER PT J AU Scharf, J Yu, DM Mathews, C Neale, B Stewart, E Fagerness, J Evans, P Gamazon, E Service, S Osiecki, L Illmann, C Cath, D King, R Dion, Y Sandor, P Barr, C Budman, C Lyon, G Grados, M Singer, H Jankovic, J Gilbert, D Hoekstra, P Heiman, G Tischfield, J State, M Robertson, M Kurlan, R Ophoff, R Gibbs, JR Cookson, M Hardy, J Singleton, A Ruiz-Linares, A Rouleau, G Heutink, P Oostra, B McMahon, W Freimer, N Cox, N Pauls, D AF Scharf, Jeremiah Yu, Dongmei Mathews, Carol Neale, Benjamin Stewart, Evelyn Fagerness, Jes Evans, Patrick Gamazon, Eric Service, Susan Osiecki, Lisa Illmann, Cornelia Cath, Danielle King, Robert Dion, Yves Sandor, Paul Barr, Cathy Budman, Cathy Lyon, Gholson Grados, Marco Singer, Harvey Jankovic, Joseph Gilbert, Donald Hoekstra, Pieter Heiman, Gary Tischfield, Jay State, Matthew Robertson, Mary Kurlan, Roger Ophoff, Roel Gibbs, J. Raphael Cookson, Mark Hardy, John Singleton, Andrew Ruiz-Linares, Andres Rouleau, Guy Heutink, Peter Oostra, Ben McMahon, William Freimer, Nelson Cox, Nancy Pauls, David TI Genome-Wide Association Study of Gilles de la Tourette Syndrome SO NEUROLOGY LA English DT Meeting Abstract CT 64th Annual Meeting of the American-Academy-of-Neurology (AAN) CY APR 21-28, 2012 CL New Orleans, LA SP Amer Acad Neurol (AAN) C1 [Yu, Dongmei; Neale, Benjamin] Ctr Human Genet Res, Psychiat & Neurodev Genet Unit, Boston, MA USA. [Stewart, Evelyn] Univ British Columbia, Vancouver, BC V5Z 1M9, Canada. [Fagerness, Jes; Osiecki, Lisa] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Mathews, Carol] Psychiat UCSF, San Francisco, CA USA. [Evans, Patrick; Gamazon, Eric; Cox, Nancy] Univ Chicago, Chicago, IL 60637 USA. [Service, Susan; Ophoff, Roel; Freimer, Nelson] Univ Calif Los Angeles, Los Angeles, CA USA. [Illmann, Cornelia] MGH, Boston, MA USA. [Cath, Danielle] Univ Utrecht, Utrecht, Netherlands. [State, Matthew] Yale Univ, Sch Med, New Haven, CT USA. [Dion, Yves; Rouleau, Guy] Univ Montreal, Montreal, PQ, Canada. [Dion, Yves; Sandor, Paul] Univ Toronto, Toronto, ON, Canada. [Budman, Cathy] N Shore LIJ Med Ctr, Manhasset, NY USA. [Lyon, Gholson] Childrens Hosp Philadephia, Philadelphia, PA USA. [Grados, Marco] Johns Hopkins Univ, Baltimore, MD USA. [Jankovic, Joseph] Baylor Coll Med, Houston, TX 77030 USA. [Gilbert, Donald] Cincinnati Childrens Med Ctr, Cincinnati, OH USA. [Hoekstra, Pieter] Univ Groningen, Groningen, Netherlands. [Heiman, Gary; Tischfield, Jay] Rutgers State Univ, Piscataway, NJ USA. [Robertson, Mary] St George Hosp, London, England. [Kurlan, Roger] Atlantic Neurosci Inst, Summit, NJ USA. [Gibbs, J. Raphael; Cookson, Mark; Singleton, Andrew] NIH, Bethesda, MD 20892 USA. [Hardy, John; Ruiz-Linares, Andres] UCL, London, England. [Heutink, Peter] Dept Clin Genet, Amsterdam, Netherlands. [Oostra, Ben] Erasmus Univ, Dept Clin Genet, NL-3000 DR Rotterdam, Netherlands. [McMahon, William] Univ Utah, Salt Lake City, UT USA. NR 0 TC 0 Z9 0 U1 1 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0028-3878 J9 NEUROLOGY JI Neurology PD APR PY 2012 VL 78 SU 1 MA IN101002 PG 4 WC Clinical Neurology SC Neurosciences & Neurology GA 931GQ UT WOS:000303204804240 ER PT J AU Scharf, J Yu, DM Mathews, C Neale, B Stewart, E Fagerness, J Evans, P Gamazon, E Service, S Osiecki, L Illmann, C Cath, D King, R Dion, Y Sandor, P Barr, C Budman, C Lyon, G Grados, M Singer, H Jankovic, J Gilbert, D Hoekstra, P Heiman, G Tischfield, J State, M Robertson, M Kurlan, R Ophoff, R Gibbs, JR Cookson, M Hardy, J Singleton, A Ruiz-Linares, A Rouleau, G Heutink, P Oostra, B McMahon, W Freimer, N Cox, N Pauls, D AF Scharf, Jeremiah Yu, Dongmei Mathews, Carol Neale, Benjamin Stewart, Evelyn Fagerness, Jes Evans, Patrick Gamazon, Eric Service, Susan Osiecki, Lisa Illmann, Cornelia Cath, Danielle King, Robert Dion, Yves Sandor, Paul Barr, Cathy Budman, Cathy Lyon, Gholson Grados, Marco Singer, Harvey Jankovic, Joseph Gilbert, Donald Hoekstra, Pieter Heiman, Gary Tischfield, Jay State, Matthew Robertson, Mary Kurlan, Roger Ophoff, Roel Gibbs, J. Raphael Cookson, Mark Hardy, John Singleton, Andrew Ruiz-Linares, Andres Rouleau, Guy Heutink, Peter Oostra, Ben McMahon, William Freimer, Nelson Cox, Nancy Pauls, David TI Genome-Wide Association Study of Gilles de la Tourette Syndrome SO NEUROLOGY LA English DT Meeting Abstract CT 64th Annual Meeting of the American-Academy-of-Neurology (AAN) CY APR 21-28, 2012 CL New Orleans, LA SP Amer Acad Neurol (AAN) C1 [Yu, Dongmei; Neale, Benjamin; Pauls, David] Ctr Human Genet Res, Psychiat & Neurodev Genet Unit, Boston, MA USA. [Mathews, Carol] Psychiat UCSF, San Francisco, CA USA. [Stewart, Evelyn] Univ British Columbia, Vancouver, BC, Canada. [Fagerness, Jes; Osiecki, Lisa; Illmann, Cornelia] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Evans, Patrick; Gamazon, Eric; Cox, Nancy] Univ Chicago, Chicago, IL 60637 USA. [Service, Susan; Ophoff, Roel; Freimer, Nelson] Univ Calif Los Angeles, Los Angeles, CA USA. [Cath, Danielle] Univ Utrecht, Utrecht, Netherlands. [State, Matthew] Yale Univ, Sch Med, New Haven, CT USA. [Dion, Yves; Rouleau, Guy] Univ Montreal, Montreal, PQ, Canada. [Sandor, Paul; Barr, Cathy] Univ Toronto, Toronto, ON, Canada. [Budman, Cathy] N Shore LIJ Med Ctr, Manhasset, NY USA. [Lyon, Gholson] Childrens Hosp Philadephia, Philadelphia, MA USA. [Grados, Marco] Johns Hopkins Univ, Baltimore, MD USA. [Singer, Harvey] Johns Hopkins, Baltimore, MD USA. [Jankovic, Joseph] Baylor Coll Med, Houston, TX 77030 USA. [Gilbert, Donald] Cincinnati Childrens Med Ctr, Cincinnati, OH USA. [Hoekstra, Pieter] Univ Groningen, Groningen, Netherlands. [Heiman, Gary; Tischfield, Jay] Rutgers State Univ, Piscataway, NJ USA. [Robertson, Mary] St George Hosp, London, England. [Kurlan, Roger] Atlantic Neurosci Inst, Summit, NJ USA. [Gibbs, J. Raphael; Cookson, Mark; Singleton, Andrew] NIH, Bethesda, MD 20892 USA. [Hardy, John; Ruiz-Linares, Andres] UCL, London, England. [Heutink, Peter] Dept Clin Genet, Amsterdam, Netherlands. [Oostra, Ben] Erasmus Univ, Dept Clin Genet, NL-3000 DR Rotterdam, Netherlands. [McMahon, William] Univ Utah, Salt Lake City, UT USA. RI Hardy, John/C-2451-2009; Singleton, Andrew/C-3010-2009; Stewart, Evelyn/K-6961-2014 NR 0 TC 0 Z9 0 U1 1 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0028-3878 J9 NEUROLOGY JI Neurology PD APR PY 2012 VL 78 SU 1 MA S32006 PG 3 WC Clinical Neurology SC Neurosciences & Neurology GA 931GQ UT WOS:000303204802034 ER PT J AU Scher, A Eiriksdottir, G Feit, P Smith, A Roecklein, K Gudmundsson, L Gudnason, V Launer, L AF Scher, Ann Eiriksdottir, Gudny Feit, Preethy Smith, Albert Roecklein, Kathryn Gudmundsson, Larus Gudnason, Vilmundur Launer, Lenore TI Selective Survival and Late-Life Risk Factor Studies SO NEUROLOGY LA English DT Meeting Abstract CT 64th Annual Meeting of the American-Academy-of-Neurology (AAN) CY APR 21-28, 2012 CL New Orleans, LA SP Amer Acad Neurol (AAN) C1 [Scher, Ann; Feit, Preethy; Gudmundsson, Larus] Uniformed Serv Univ Hlth Sci, Bethesda, MD USA. [Eiriksdottir, Gudny; Smith, Albert; Gudnason, Vilmundur] Iceland Heart Assoc, Kopavogur, Iceland. [Roecklein, Kathryn] Univ Pittsburgh, Dept Psychol, Pittsburgh, PA 15260 USA. [Launer, Lenore] NIA, Washington, DC USA. RI Gudnason, Vilmundur/K-6885-2015 OI Gudnason, Vilmundur/0000-0001-5696-0084 NR 0 TC 0 Z9 0 U1 1 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0028-3878 J9 NEUROLOGY JI Neurology PD APR PY 2012 VL 78 SU 1 MA P04246 PG 2 WC Clinical Neurology SC Neurosciences & Neurology GA 931GQ UT WOS:000303204802210 ER PT J AU Sheth, K Koch, S Elkind, M Sung, G Kittner, S Frankel, M Rosand, J Langefeld, C Comeau, M Waddy, S Osborne, J Woo, D AF Sheth, Kevin Koch, Sebastian Elkind, Mitchell Sung, Gene Kittner, Steven Frankel, Michael Rosand, Jonathan Langefeld, Carl Comeau, Mary Waddy, Salina Osborne, Jennifer Woo, Daniel CA ERICH Investigators TI Anti-Epileptic Drug Use and Outcome in the Ethnic and Racial Variations in Intracerebral Hemorrhage (ERICH) Study SO NEUROLOGY LA English DT Meeting Abstract CT 64th Annual Meeting of the American-Academy-of-Neurology (AAN) CY APR 21-28, 2012 CL New Orleans, LA SP Amer Acad Neurol (AAN) C1 [Sheth, Kevin] Univ Maryland, Sch Med, Baltimore, MD 21201 USA. [Koch, Sebastian] Univ Miami, Miller Sch Med, Miami, FL 33136 USA. [Elkind, Mitchell] Columbia Univ, New York, NY USA. [Sung, Gene] Univ So Calif, Los Angeles, CA USA. [Frankel, Michael] Emory Univ, Sch Med, Atlanta, GA USA. [Rosand, Jonathan] MGH, Boston, MA USA. [Langefeld, Carl] Wake Forest Sch Med, Winston Salem, NC USA. [Comeau, Mary] Wake Forest Publ Hlth Sci, Winston Salem, NC USA. [Waddy, Salina] NIH, Washington, DC USA. [Osborne, Jennifer; Woo, Daniel; ERICH Investigators] Univ Cincinnati, Cincinnati, OH USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0028-3878 J9 NEUROLOGY JI Neurology PD APR PY 2012 VL 78 SU 1 MA S23005 PG 3 WC Clinical Neurology SC Neurosciences & Neurology GA 931GQ UT WOS:000303204801554 ER PT J AU Sweeney, E Shinohara, R Shea, C Reich, D Crainiceanu, C AF Sweeney, Elizabeth Shinohara, Russell Shea, Colin Reich, Daniel Crainiceanu, Ciprian TI Lesion Incidence Estimation and Detection Using Multi-Modality Longitudinal MRIs SO NEUROLOGY LA English DT Meeting Abstract CT 64th Annual Meeting of the American-Academy-of-Neurology (AAN) CY APR 21-28, 2012 CL New Orleans, LA SP Amer Acad Neurol (AAN) C1 [Sweeney, Elizabeth; Shinohara, Russell; Crainiceanu, Ciprian] Johns Hopkins Univ, Dept Biostat, Baltimore, MD 21205 USA. [Shea, Colin; Reich, Daniel] Natl Inst Neurol Disorder & Stroke, Bethesda, MD USA. RI Reich, Daniel/E-5701-2010 OI Reich, Daniel/0000-0002-2628-4334 NR 0 TC 0 Z9 0 U1 1 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0028-3878 J9 NEUROLOGY JI Neurology PD APR PY 2012 VL 78 SU 1 MA P03069 PG 2 WC Clinical Neurology SC Neurosciences & Neurology GA 931GQ UT WOS:000303204801526 ER PT J AU Theodore, W Dustin, I Khan, O Hodgkinson, C Akhtar, L Goldman, D AF Theodore, William Dustin, Irene Khan, Omar Hodgkinson, Coiln Akhtar, Longina Goldman, David TI Reduced Serotonin Transporter Promoter Activity in Mesial Temporal Sclerosis and Temporal Lobe Epilepsy SO NEUROLOGY LA English DT Meeting Abstract CT 64th Annual Meeting of the American-Academy-of-Neurology (AAN) CY APR 21-28, 2012 CL New Orleans, LA SP Amer Acad Neurol (AAN) C1 [Theodore, William; Dustin, Irene; Khan, Omar] NIH, Bethesda, MD 20892 USA. [Hodgkinson, Coiln; Akhtar, Longina; Goldman, David] NIH, Rockville, MD USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0028-3878 J9 NEUROLOGY JI Neurology PD APR PY 2012 VL 78 SU 1 MA S26007 PG 1 WC Clinical Neurology SC Neurosciences & Neurology GA 931GQ UT WOS:000303204801570 ER PT J AU Theodore, W Dustin, I Khan, O Hodgkinson, C Akhtar, L Goldman, D AF Theodore, William Dustin, Irene Khan, Omar Hodgkinson, Coiln Akhtar, Longina Goldman, David TI Reduced Serotonin Transporter Promoter Activity in Mesial Temporal Sclerosis and Temporal Lobe Epilepsy SO NEUROLOGY LA English DT Meeting Abstract CT 64th Annual Meeting of the American-Academy-of-Neurology (AAN) CY APR 21-28, 2012 CL New Orleans, LA SP Amer Acad Neurol (AAN) C1 [Theodore, William; Dustin, Irene; Khan, Omar] NIH, Bethesda, MD 20892 USA. [Hodgkinson, Coiln; Akhtar, Longina; Goldman, David] NIH, Rockville, MD USA. NR 0 TC 0 Z9 0 U1 1 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0028-3878 J9 NEUROLOGY JI Neurology PD APR PY 2012 VL 78 SU 1 MA IN52001 PG 3 WC Clinical Neurology SC Neurosciences & Neurology GA 931GQ UT WOS:000303204800042 ER PT J AU Vanderver, A Tonduti, D Lebon, P Blau, N Loewenstein, J Gahl, W Toro, C Hyland, K AF Vanderver, Adeline Tonduti, Davide Lebon, Pierre Blau, Nenad Loewenstein, Johanna Gahl, William Toro, Camilo Hyland, Keith TI Neurotransmitter Abnormalities and Response to L-Dopa in SPG11 SO NEUROLOGY LA English DT Meeting Abstract CT 64th Annual Meeting of the American-Academy-of-Neurology (AAN) CY APR 21-28, 2012 CL New Orleans, LA SP Amer Acad Neurol (AAN) C1 [Vanderver, Adeline; Loewenstein, Johanna] Childrens Natl Med Ctr, Washington, DC 20010 USA. [Tonduti, Davide] IRCCS C Mondino Inst Neurol Fdn, Pavia, Italy. [Lebon, Pierre] Univ Paris 05, Hop Cochin Paris, Paris, France. [Blau, Nenad] Zurich ZH, Zurich, Switzerland. [Gahl, William] NHGRI, NIH, Bethesda, MD 20892 USA. [Toro, Camilo] NINDS, NIH, Frederick, MD USA. RI tonduti, davide/K-1673-2016 OI tonduti, davide/0000-0001-9371-7454 NR 0 TC 0 Z9 0 U1 1 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0028-3878 J9 NEUROLOGY JI Neurology PD APR PY 2012 VL 78 SU 1 MA P05133 PG 2 WC Clinical Neurology SC Neurosciences & Neurology GA 931GQ UT WOS:000303204802487 ER PT J AU Wojna, V Curry, T Haughey, N Bandaru, V Skolasky, R Hachavarria, R Mayo, R Bryant, C Anderson, C Fernandez, M Velez, J Nath, A AF Wojna, Valerie Curry, Thomas Haughey, Norman Bandaru, Veera Skolasky, Richard Hachavarria, Rosa Mayo, Raul Bryant, Carole Anderson, Carole Fernandez, Mayra Velez, Joyce Nath, Avindra TI Gonadal Hormone Dysfunction Modulates CSF Oxidative Stress Markers in HIV-Seropositive Women with Cognitive Impairment SO NEUROLOGY LA English DT Meeting Abstract CT 64th Annual Meeting of the American-Academy-of-Neurology (AAN) CY APR 21-28, 2012 CL New Orleans, LA SP Amer Acad Neurol (AAN) C1 [Wojna, Valerie] Univ Puerto Rico, Div Neurol, San Juan, PR 00936 USA. [Wojna, Valerie; Hachavarria, Rosa; Mayo, Raul; Fernandez, Mayra; Velez, Joyce] Univ Puerto Rico, NeuroAIDS Program, San Juan, PR 00936 USA. [Curry, Thomas; Bryant, Carole] Univ Kentucky, Div Reprod Endocrinol, Lexington, KY USA. [Haughey, Norman; Bandaru, Veera] Johns Hopkins Univ, Dept Neurol, Baltimore, MD 21218 USA. [Skolasky, Richard] Johns Hopkins Univ, Dept Orthopaed, Baltimore, MD USA. [Anderson, Carole; Nath, Avindra] NINDS, Sect Infect Nervous Syst, NIH, Baltimore, MD USA. NR 0 TC 0 Z9 0 U1 1 U2 4 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0028-3878 J9 NEUROLOGY JI Neurology PD APR PY 2012 VL 78 SU 1 MA S37002 PG 2 WC Clinical Neurology SC Neurosciences & Neurology GA 931GQ UT WOS:000303204802073 ER PT J AU Wolinsky, J Narayana, P Nelson, F Datta, S Cofield, S Cutter, G Conwit, R Gustafson, T Lublin, F AF Wolinsky, Jerry Narayana, Ponnada Nelson, Flavia Datta, Sushmita Cofield, Stacey Cutter, Gary Conwit, Robin Gustafson, Tarah Lublin, Fred CA CombiRx Investigators TI The CombiRx Trial: A Multi-Center, Double-Blind, Randomized Study Comparing the Combined Use of Interferon Beta-1a and Glatiramer Acetate to Either Agent Alone in Participants with Relapsing Remitting Multiple Sclerosis - MRI Outcomes SO NEUROLOGY LA English DT Meeting Abstract CT 64th Annual Meeting of the American-Academy-of-Neurology (AAN) CY APR 21-28, 2012 CL New Orleans, LA SP Amer Acad Neurol (AAN) C1 [Wolinsky, Jerry; Narayana, Ponnada; Nelson, Flavia; Datta, Sushmita] Univ Texas Hlth Sci Ctr Texas, Houston, TX USA. [Cofield, Stacey; Cutter, Gary] Univ Alabama Birmingham, Birmingham, AL USA. [Conwit, Robin] NINDS, NIH, Lutherville Timonium, MD USA. [Gustafson, Tarah; Lublin, Fred; CombiRx Investigators] Mt Sinai Sch Med, New York, NY USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0028-3878 J9 NEUROLOGY JI Neurology PD APR PY 2012 VL 78 SU 1 MA S11002 PG 3 WC Clinical Neurology SC Neurosciences & Neurology GA 931GQ UT WOS:000303204804260 ER PT J AU Zhuang, P Hallett, M Dong, S Zhang, XH Zhang, YQ Li, JY Li, YJ AF Zhuang, Ping Hallett, Mark Dong, Sheng Zhang, Xiaohua Zhang, Yuqing Li, Jianyu Li, Yongjie TI Electrode Contact Location Correlates with the Location of Tic-Related Neuronal Activity in the Globus Pallidus Internus in Patients with Tics SO NEUROLOGY LA English DT Meeting Abstract CT 64th Annual Meeting of the American-Academy-of-Neurology (AAN) CY APR 21-28, 2012 CL New Orleans, LA SP Amer Acad Neurol (AAN) C1 [Zhuang, Ping; Dong, Sheng; Zhang, Xiaohua; Zhang, Yuqing; Li, Jianyu; Li, Yongjie] Capital Med Univ, Xuanwu Hosp, Beijing Inst Funct Neurosurg, Beijing, Peoples R China. [Hallett, Mark] NINDS, Human Motor Sect, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 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 APR PY 2012 VL 78 SU 1 MA P01.189 PG 3 WC Clinical Neurology SC Neurosciences & Neurology GA 931GQ UT WOS:000303204800217 ER PT J AU Fernandez, MA Rueda, C Peddada, SD AF Fernandez, Miguel A. Rueda, Cristina Peddada, Shyamal D. TI Identification of a core set of signature cell cycle genes whose relative order of time to peak expression is conserved across species SO NUCLEIC ACIDS RESEARCH LA English DT Article ID REGULATED GENES; FISSION YEAST; SACCHAROMYCES-CEREVISIAE; EXPONENTIAL-FAMILIES; RESTRICTIONS; ARABIDOPSIS; CHECKPOINTS; NETWORK; DAMAGE; POMBE AB A cell division cycle is a well-coordinated process in eukaryotes with cell cycle genes exhibiting a periodic expression over time. There is considerable interest among cell biologists to determine genes that are periodic in multiple organisms and whether such genes are also evolutionarily conserved in their relative order of time to peak expression. Interestingly, periodicity is not well-conserved evolutionarily. A conservative estimate of a number of periodic genes common to fission yeast (Schizosaccharomyces pombe) and budding yeast (Saccharomyces cerevisiae) ('core set FB') is 35, while those common to fission yeast and humans (Homo sapiens) ('core set FH') is 24. Using a novel statistical methodology, we discover that the relative order of peak expression is conserved in similar to 80% of FB genes and in similar to 40% of FH genes. We also discover that the order is evolutionarily conserved in six genes which are potentially the core set of signature cell cycle genes. These include ace2 (a transcription factor) and polo-kinase plo1, which are well-known hubs of early M-phase clusters, cdc18 a key component of pre-replication complexes, mik1 which is critical for the establishment and maintenance of DNA damage check point, and histones hhf1 and hta2. C1 [Peddada, Shyamal D.] NIEHS, Biostat Branch, Res Triangle Pk, NC 27709 USA. [Fernandez, Miguel A.; Rueda, Cristina] Univ Valladolid, Dept Stat & Operat Res, E-47005 Valladolid, Spain. RP Peddada, SD (reprint author), NIEHS, Biostat Branch, Alexander Dr, Res Triangle Pk, NC 27709 USA. EM peddada@niehs.nih.gov RI Peddada, Shyamal/D-1278-2012; Fernandez, Miguel/I-2874-2015 OI Fernandez, Miguel/0000-0002-1272-8950 FU Spanish Ministerio de Ciencia e Innovacion [MTM2009-11161]; National Institutes of Health, National Institute of Environmental Health Sciences [Z01 ES101744-04]; Biostatistics Branch, NIEHS, National Institutes of Health FX Spanish Ministerio de Ciencia e Innovacion (MTM2009-11161 to M.A.F. and C.R.); Intramural Research Program of the National Institutes of Health, National Institute of Environmental Health Sciences (Z01 ES101744-04). Funding for open access charge: Biostatistics Branch, NIEHS, National Institutes of Health. NR 31 TC 10 Z9 10 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 APR PY 2012 VL 40 IS 7 BP 2823 EP 2832 DI 10.1093/nar/gkr1077 PG 10 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 930TQ UT WOS:000303164400009 PM 22135306 ER PT J AU Kidder, BL Palmer, S AF Kidder, Benjamin L. Palmer, Stephen TI HDAC1 regulates pluripotency and lineage specific transcriptional networks in embryonic and trophoblast stem cells SO NUCLEIC ACIDS RESEARCH LA English DT Article ID HISTONE DEACETYLASE 1; GENE-EXPRESSION; CHROMATIN-STRUCTURE; POLYCOMB-GROUP; SELF-RENEWAL; DIFFERENTIATION; OCT4; REVEALS; COMPLEX; NANOG AB Epigenetic regulation of gene expression is important in maintaining self-renewal of embryonic stem (ES) and trophoblast stem (TS) cells. Histone deacetylases (HDACs) negatively control histone acetylation by removing covalent acetylation marks from histone tails. Because histone acetylation is a known mark for active transcription, HDACs presumably associate with inactive genes. Here, we used genome-wide chromatin immunoprecipitation to investigate targets of HDAC1 in ES and TS cells. Through evaluation of genes associated with acetylated histone H3 marks, and global expression analysis of Hdac1 knockout ES and trichostatin A-treated ES and TS cells, we found that HDAC1 occupies mainly active genes, including important regulators of ES and TS cells self-renewal. We also observed occupancy of methyl-CpG binding domain protein 3 (MBD3), a subunit of the nucleosome remodeling and histone deacetylation (NuRD) complex, at a subset of HDAC1-occupied sequences in ES cells, including the pluripotency regulators Oct4, Nanog and Kfl4. By mapping HDAC1 targets on a global scale, our results describe further insight into epigenetic mechanisms of ES and TS cells self-renewal. C1 [Kidder, Benjamin L.; Palmer, Stephen] EMD Serono Res Inst, Billerica, MA 01821 USA. [Kidder, Benjamin L.] NHLBI, Syst Biol Ctr, NIH, Bethesda, MD 20892 USA. RP Kidder, BL (reprint author), EMD Serono Res Inst, Billerica, MA 01821 USA. EM Benjamin.kidder@nih.gov FU EMD Serono Research Institute, Inc.; EMD Serono Research Institute FX This work was funded by an internal grant at EMD Serono Research Institute, Inc. Funding for open access charge: EMD Serono Research Institute. NR 44 TC 51 Z9 51 U1 0 U2 5 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0305-1048 J9 NUCLEIC ACIDS RES JI Nucleic Acids Res. PD APR PY 2012 VL 40 IS 7 BP 2925 EP 2939 DI 10.1093/nar/gkr1151 PG 15 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 930TQ UT WOS:000303164400017 PM 22156375 ER PT J AU Kirby, TW DeRose, EF Cavanaugh, NA Beard, WA Shock, DD Mueller, GA Wilson, SH London, RE AF Kirby, Thomas W. DeRose, Eugene F. Cavanaugh, Nisha A. Beard, William A. Shock, David D. Mueller, Geoffrey A. Wilson, Samuel H. London, Robert E. TI Metal-induced DNA translocation leads to DNA polymerase conformational activation SO NUCLEIC ACIDS RESEARCH LA English DT Article ID HIV-1 REVERSE-TRANSCRIPTASE; BASE EXCISION-REPAIR; NUCLEOTIDE INCORPORATION; MAGNETIC-RESONANCE; MITOCHONDRIAL-DNA; GASTRIC-CANCER; ABASIC SITE; IN-VITRO; BETA; MECHANISM AB Binding of the catalytic divalent ion to the ternary DNA polymerase beta/gapped DNA/dNTP complex is thought to represent the final step in the assembly of the catalytic complex and is consequently a critical determinant of replicative fidelity. We have analyzed the effects of Mg2+ and Zn2+ on the conformational activation process based on NMR measurements of [methyl-C-13]methionine DNA polymerase beta. Unexpectedly, both divalent metals were able to produce a template base-dependent conformational activation of the polymerase/1-nt gapped DNA complex in the absence of a complementary incoming nucleotide, albeit with different temperature thresholds. This conformational activation is abolished by substituting Glu295 with lysine, thereby interrupting key hydrogen bonds necessary to stabilize the closed conformation. These and other results indicate that metal-binding can promote: translocation of the primer terminus base pair into the active site; expulsion of an unpaired pyrimidine, but not purine, base from the template-binding pocket; and motions of polymerase subdomains that close the active site. We also have performed pyrophosphorolysis studies that are consistent with predictions based on these results. These findings provide new insight into the relationships between conformational activation, enzyme activity and polymerase fidelity. C1 [Kirby, Thomas W.; DeRose, Eugene F.; Cavanaugh, Nisha A.; Beard, William A.; Shock, David D.; Mueller, Geoffrey A.; Wilson, Samuel H.; London, Robert E.] NIEHS, Struct Biol Lab, Res Triangle Pk, NC 27709 USA. RP London, RE (reprint author), NIEHS, Struct Biol Lab, POB 12233, Res Triangle Pk, NC 27709 USA. EM london@niehs.nih.gov FU National Institute of Environmental Health Sciences, National Institutes of Health [Z01-ES050147, Z01-ES050158]; association with National Institutes of Health [1U19CA105010]; National Institute of Environmental Health Sciences FX Intramural research program of the National Institute of Environmental Health Sciences, National Institutes of Health, under projects (Z01-ES050147 to R.E.L.) and (Z01-ES050158 to S.H.W.), in association with National Institutes of Health (Grant 1U19CA105010). Funding for open access charge: Research Project Numbers (Z01-ES050147 to R.E.L. and Z01-ES050158 to S.H.W.). National Institute of Environmental Health Sciences. NR 42 TC 15 Z9 15 U1 1 U2 14 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0305-1048 J9 NUCLEIC ACIDS RES JI Nucleic Acids Res. PD APR PY 2012 VL 40 IS 7 BP 2974 EP 2983 DI 10.1093/nar/gkr1218 PG 10 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 930TQ UT WOS:000303164400021 PM 22169953 ER PT J AU Chen, B Zuo, XB Wang, YX Dayie, TK AF Chen, Bin Zuo, Xiaobing Wang, Yun-Xing Dayie, T. Kwaku TI Multiple conformations of SAM-II riboswitch detected with SAXS and NMR spectroscopy SO NUCLEIC ACIDS RESEARCH LA English DT Article ID X-RAY-SCATTERING; GLYCINE-DEPENDENT RIBOSWITCH; MESSENGER-RNA ELEMENT; S-MK BOX; INDUCED FIT; SENSING RIBOSWITCH; GENE-EXPRESSION; APTAMER DOMAIN; BIOLOGICAL MACROMOLECULES; ADAPTIVE RECOGNITION AB Riboswitches are a newly discovered large family of structured functional RNA elements that specifically bind small molecule targets out of a myriad of cellular metabolites to modulate gene expression. Structural studies of ligand-bound riboswitches by X-ray crystallography and nuclear magnetic resonance (NMR) spectroscopy have provided insights into detailed RNA-ligand recognition and interactions. However, the structures of ligand-free riboswitches remain poorly characterized. In this study, we have used a variety of biochemical, biophysical and computational techniques including small-angle X-ray scattering and NMR spectroscopy to characterize the ligand-free and ligand-bound forms of SAM-II riboswitch. Our data demonstrate that the RNA adopts multiple conformations along its folding pathway and suggest that the RNA undergoes marked conformational changes upon Mg2+ compaction and S-adenosylmethionine (SAM) metabolite binding. Further studies indicated that Mg2+ ion is not essential for the ligand binding but can stabilize the complex by facilitating loop/stem interactions. In the presence of millimolar concentration of Mg2+ ion, the RNA samples a more compact conformation. This conformation is near to, but distinct from, the native fold and competent to bind the metabolite. We conclude that the formation of various secondary and tertiary structural elements, including a pseudoknot, occur to sequester the putative Shine-Dalgarno sequence of the RNA only after metabolite binding. C1 [Chen, Bin; Dayie, T. Kwaku] Univ Maryland, Dept Chem & Biochem, College Pk, MD 20742 USA. [Zuo, Xiaobing; Wang, Yun-Xing] NCI, Prot Nucle Acid Interact Sect, Struct Biophys Lab, Ctr Canc Res,NIH, Frederick, MD 21702 USA. RP Dayie, TK (reprint author), Univ Maryland, Dept Chem & Biochem, College Pk, MD 20742 USA. EM dayie@umd.edu RI Zuo, Xiaobing/F-1469-2010; Dayie, T Kwaku/E-6868-2011 OI Dayie, T Kwaku/0000-0002-7119-4362 FU US DOE; University of Maryland; National Institutes of Health [GM077326] FX National Cancer Institute and Beamline 12-ID at Argonne National Laboratory. The authors also thank Dr Robert T. Batey for kindly providing the plasmid. DE-AC02-06CH11357). The authors thank X-ray scattering beam time resource through PUP-21086/22978 between Office of Science by Argonne National Laboratory, was supported by the US DOE (under Contract No. Use of the Advanced Photon Source, an Office of Science User Facility operated for the US Department of Energy (DOE).; University of Maryland Nano-Biotechnology Award (partial); National Institutes of Health grant (GM077326 to T. K. D., partial). Funding for open access charge: NIH. NR 80 TC 32 Z9 33 U1 2 U2 28 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 APR PY 2012 VL 40 IS 7 BP 3117 EP 3130 DI 10.1093/nar/gkr1154 PG 14 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 930TQ UT WOS:000303164400033 PM 22139931 ER PT J AU Freudenberg, JM Ghosh, S Lackford, BL Yellaboina, S Zheng, XF Li, RF Cuddapah, S Wade, PA Hu, G Jothi, R AF Freudenberg, Johannes M. Ghosh, Swati Lackford, Brad L. Yellaboina, Sailu Zheng, Xiaofeng Li, Ruifang Cuddapah, Suresh Wade, Paul A. Hu, Guang Jothi, Raja TI Acute depletion of Tet1-dependent 5-hydroxymethylcytosine levels impairs LIF/Stat3 signaling and results in loss of embryonic stem cell identity SO NUCLEIC ACIDS RESEARCH LA English DT Article ID ACTIVE DNA DEMETHYLATION; MOUSE ES CELLS; CHROMATIN REMODELING COMPLEX; SELF-RENEWAL; TET PROTEINS; RNAI SCREEN; TRANSCRIPTIONAL NETWORK; MYELOID CANCERS; MAMMALIAN DNA; HUMAN GENOME AB The TET family of FE(II) and 2-oxoglutarate-dependent enzymes (Tet1/2/3) promote DNA demethylation by converting 5-methylcytosine to 5-hydroxymethylcytosine (5hmC), which they further oxidize into 5-formylcytosine and 5-carboxylcytosine. Tet1 is robustly expressed in mouse embryonic stem cells (mESCs) and has been implicated in mESC maintenance. Here we demonstrate that, unlike genetic deletion, RNAi-mediated depletion of Tet1 in mESCs led to a significant reduction in 5hmC and loss of mESC identity. The differentiation phenotype due to Tet1 depletion positively correlated with the extent of 5hmC loss. Meta-analyses of genomic data sets suggested interaction between Tet1 and leukemia inhibitory factor (LIF) signaling. LIF signaling is known to promote self-renewal and pluripotency in mESCs partly by opposing MAPK/ERK-mediated differentiation. Withdrawal of LIF leads to differentiation of mESCs. We discovered that Tet1 depletion impaired LIF-dependent Stat3-mediated gene activation by affecting Stat3's ability to bind to its target sites on chromatin. Nanog overexpression or inhibition of MAPK/ERK signaling, both known to maintain mESCs in the absence of LIF, rescued Tet1 depletion, further supporting the dependence of LIF/Stat3 signaling on Tet1. These data support the conclusion that analysis of mESCs in the hours/days immediately following efficient Tet1 depletion reveals Tet1's normal physiological role in maintaining the pluripotent state that may be subject to homeostatic compensation in genetic models. C1 [Lackford, Brad L.; Zheng, Xiaofeng; Li, Ruifang; Wade, Paul A.; Hu, Guang] NIEHS, Mol Carcinogenesis Lab, NIH, Res Triangle Pk, NC 27709 USA. [Freudenberg, Johannes M.; Ghosh, Swati; Yellaboina, Sailu; Jothi, Raja] NIEHS, Syst Biol Sect, Biostat Branch, NIH, Res Triangle Pk, NC 27709 USA. [Cuddapah, Suresh] NYU, Sch Med, Dept Environm Med, Tuxedo Pk, NY 10987 USA. RP Jothi, R (reprint author), NIEHS, Syst Biol Sect, Biostat Branch, NIH, 111 TW Alexander Dr, Res Triangle Pk, NC 27709 USA. EM hug4@niehs.nih.gov; jothi@mail.nih.gov RI Waha, Andreas/J-2950-2014; Jothi, Raja/G-3780-2015; Hu, Guang/E-7474-2016 OI Hu, Guang/0000-0003-0437-4723 FU NIH, National Institute of Environmental Health Sciences [1ZIAES102625-03, 1ZIAES102745-02, 1ZIAES101965-07] FX Funding for open access charge: The Intramural Research Program of the NIH, National Institute of Environmental Health Sciences [1ZIAES102625-03 (to R.J.), 1ZIAES102745-02 (to G.H.) and 1ZIAES101965-07 (to P.A.W.)]. NR 79 TC 49 Z9 50 U1 0 U2 14 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0305-1048 EI 1362-4962 J9 NUCLEIC ACIDS RES JI Nucleic Acids Res. PD APR PY 2012 VL 40 IS 8 BP 3364 EP 3377 DI 10.1093/nar/gkr1253 PG 14 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 933BF UT WOS:000303333500014 PM 22210859 ER PT J AU Hudson, RS Yi, M Esposito, D Watkins, SK Hurwitz, AA Yfantis, HG Lee, DH Borin, JF Naslund, MJ Alexander, RB Dorsey, TH Stephens, RM Croce, CM Ambs, S AF Hudson, Robert S. Yi, Ming Esposito, Dominic Watkins, Stephanie K. Hurwitz, Arthur A. Yfantis, Harris G. Lee, Dong H. Borin, James F. Naslund, Michael J. Alexander, Richard B. Dorsey, Tiffany H. Stephens, Robert M. Croce, Carlo M. Ambs, Stefan TI MicroRNA-1 is a candidate tumor suppressor and prognostic marker in human prostate cancer SO NUCLEIC ACIDS RESEARCH LA English DT Article ID CHRONIC LYMPHOCYTIC-LEUKEMIA; DOWN-REGULATION; MESSENGER-RNAS; EXPRESSION; CELLS; GENE; ADENOCARCINOMA; SIGNATURES; PROFILES; MOUSE AB We previously reported that miR-1 is among the most consistently down-regulated miRs in primary human prostate tumors. In this follow-up study, we further corroborated this finding in an independent data set and made the novel observation that miR-1 expression is further reduced in distant metastasis and is a candidate predictor of disease recurrence. Moreover, we performed in vitro experiments to explore the tumor suppressor function of miR-1. Cell-based assays showed that miR-1 is epigenetically silenced in human prostate cancer. Overexpression of miR-1 in these cells led to growth inhibition and down-regulation of genes in pathways regulating cell cycle progression, mitosis, DNA replication/repair and actin dynamics. This observation was further corroborated with protein expression analysis and 3'-UTR-based reporter assays, indicating that genes in these pathways are either direct or indirect targets of miR-1. A gene set enrichment analysis revealed that the miR-1-mediated tumor suppressor effects are globally similar to those of histone deacetylase inhibitors. Lastly, we obtained preliminary evidence that miR-1 alters the cellular organization of F-actin and inhibits tumor cell invasion and filipodia formation. In conclusion, our findings indicate that miR-1 acts as a tumor suppressor in prostate cancer by influencing multiple cancer-related processes and by inhibiting cell proliferation and motility. C1 [Hudson, Robert S.; Dorsey, Tiffany H.; Ambs, Stefan] NCI, Human Carcinogenesis Lab, CCR, NIH, Bethesda, MD 20892 USA. [Yi, Ming; Stephens, Robert M.] SAIC Frederick Inc, Adv Biomed Comp Ctr, Frederick, MD USA. [Esposito, Dominic] SAIC Frederick Inc, Prot Express Lab, Adv Technol Program, Frederick, MD USA. [Watkins, Stephanie K.; Hurwitz, Arthur A.] NCI Frederick, Mol Immunoregulat Lab, Frederick, MD USA. [Yfantis, Harris G.; Lee, Dong H.] Univ Maryland, Baltimore Vet Affairs Med Ctr, Baltimore, MD 21201 USA. [Borin, James F.; Naslund, Michael J.; Alexander, Richard B.] Univ Maryland, Urol & Greenebaum Canc Ctr, Baltimore, MD 21201 USA. [Croce, Carlo M.] Ohio State Univ, Ctr Comprehens Canc, Dept Mol Virol Immunol & Med Genet, Columbus, OH 43210 USA. RP Ambs, S (reprint author), NCI, Human Carcinogenesis Lab, CCR, NIH, Bldg 37, Bethesda, MD 20892 USA. EM ambss@mail.nih.gov RI Jackson, Benjamin/C-4297-2012; OI Borin, James/0000-0002-1217-1566 FU National Institutes of Health (NIH), National Cancer Institute, Center for Cancer Research; Center for Cancer Research, NIH; University of Maryland, Departments of Pathology and Epidemiology FX Intramural Research Program of the National Institutes of Health (NIH), National Cancer Institute, Center for Cancer Research. Funding for open access charge: Center for Cancer Research, NIH.; We would like to thank Barbara J. Taylor at the NCI FACS Core Laboratory and Judith A. Welsh at the Laboratory of Human Carcinogenesis for technical help. We would also like to thank staff at the University of Maryland, Departments of Pathology and Epidemiology for their support with the collection of human tissue samples. NR 58 TC 65 Z9 74 U1 2 U2 15 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 APR PY 2012 VL 40 IS 8 BP 3689 EP 3703 DI 10.1093/nar/gkr1222 PG 15 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 933BF UT WOS:000303333500039 PM 22210864 ER PT J AU Jonsson, H Aspelund, T Eiriksdottir, G Tamm, A Kisand, K Franzson, L Hauksdottir, AM Harris, TB Launer, LL Gudnason, V AF Jonsson, H. Aspelund, T. Eiriksdottir, G. Tamm, A. Kisand, K. Franzson, L. Hauksdottir, A. M. Harris, T. B. Launer, L. Lenore Gudnason, V. TI LOW SERUM CONCENTRATIONS OF SERUM VEGF-R2 IN ELDERLY FEMALES WITH THUMB BASE OSTEOARTHRITIS: THE AGES-REYKJAVIK STUDY. SO OSTEOARTHRITIS AND CARTILAGE LA English DT Meeting Abstract CT World Congress on Osteoarthritis CY APR 26-29, 2012 CL Barcelona, SPAIN C1 [Jonsson, H.; Franzson, L.] Univ Iceland, Landspitalinn, Reykjavik, Iceland. [Aspelund, T.; Eiriksdottir, G.; Hauksdottir, A. M.; Gudnason, V.] Iceland Heart Assoc, Kopavogur, Iceland. [Aspelund, T.; Gudnason, V.] Univ Iceland, Reykjavik, Iceland. [Tamm, A.; Kisand, K.] Univ Tartu, EE-50090 Tartu, Estonia. [Harris, T. B.; Launer, L. Lenore] NIA, Bethesda, MD 20892 USA. RI Aspelund, Thor/C-5983-2008; Gudnason, Vilmundur/K-6885-2015; Kisand, Kalle/S-5958-2016 OI Aspelund, Thor/0000-0002-7998-5433; Gudnason, Vilmundur/0000-0001-5696-0084; Kisand, Kalle/0000-0002-7789-5565 NR 0 TC 0 Z9 0 U1 0 U2 3 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 1063-4584 J9 OSTEOARTHR CARTILAGE JI Osteoarthritis Cartilage PD APR PY 2012 VL 20 SU 1 BP S93 EP S94 PG 2 WC Orthopedics; Rheumatology SC Orthopedics; Rheumatology GA 931MF UT WOS:000303223300203 ER PT J AU Glasgow, RE Kurz, D King, D Dickman, JM Faber, AJ Halterman, E Woolley, T Toobert, DJ Strycker, LA Estabrooks, PA Osuna, D Ritzwoller, D AF Glasgow, Russell E. Kurz, Deanna King, Diane Dickman, Jennifer M. Faber, Andrew J. Halterman, Eve Woolley, Tim Toobert, Deborah J. Strycker, Lisa A. Estabrooks, Paul A. Osuna, Diego Ritzwoller, Debra TI Twelve-month outcomes of an Internet-based diabetes self-management support program SO PATIENT EDUCATION AND COUNSELING LA English DT Article DE Diabetes; Self-management; RCT; Internet intervention; Pragmatic trial; Multiple behavior change ID PHYSICAL-ACTIVITY; PRIMARY-CARE; WEIGHT-LOSS; FOLLOW-UP; INTERVENTIONS; BEHAVIOR; TRIAL; ADULTS; RECRUITMENT; PREVENTION AB Objective: Internet-based programs offer potential for practical, cost-effective chronic illness self-management programs. Methods: We report 12-month results of an Internet-based diabetes self-management program, with and without additional support, compared to enhanced usual care in a 3-arm practical randomized trial. Patients (n = 463) were randomized: 77.3% completed 12-month follow-up. Primary outcomes were changes in health behaviors of healthy eating, physical activity, and medication taking. Secondary outcomes were hemoglobin A1c, body mass index, lipids, blood pressure, and psychosocial factors. Results: Internet conditions improved health behaviors significantly vs. usual care over the 12-month period (d for effect size = .09-.16). All conditions improved moderately on biological and psychosocial outcomes. Latinos, lower literacy, and higher cardiovascular disease risk patients improved as much as other participants. Conclusions: The Internet intervention meets the reach and feasibility criteria for a potentially broad public health impact. However, 12-month magnitude of effects was small, suggesting that different or more intensive approaches are necessary to support long-term outcomes. Research is needed to understand the linkages between intervention and maintenance processes and downstream outcomes. Practice implications: Automated self-management interventions should be tailored and integrated into primary care; maintenance of patient self-management can be enhanced through links to community resources. Published by Elsevier Ireland Ltd. C1 [Glasgow, Russell E.] NCI, Div Canc Control & Populat Sci, Rockville, MD 20852 USA. [Glasgow, Russell E.; Kurz, Deanna; King, Diane; Dickman, Jennifer M.; Faber, Andrew J.; Halterman, Eve; Osuna, Diego; Ritzwoller, Debra] Kaiser Permanente Colorado, Inst Hlth Res, Denver, CO USA. [Toobert, Deborah J.; Strycker, Lisa A.] Oregon Res Inst, Eugene, OR 97403 USA. [Woolley, Tim] InterVis Media, Eugene, OR USA. [Estabrooks, Paul A.] Virginia Polytech Inst & State Univ, Roanoke, VA USA. RP Glasgow, RE (reprint author), NCI, Div Canc Control & Populat Sci, 6130 Execut Blvd,Room 6144, Rockville, MD 20852 USA. EM glasgowre@mail.nih.gov FU National Institute of Diabetes and Digestive and Kidney Diseases [DK35524] FX This study was supported by grant DK35524 from the National Institute of Diabetes and Digestive and Kidney Diseases. NR 53 TC 62 Z9 62 U1 4 U2 27 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0738-3991 J9 PATIENT EDUC COUNS JI Patient Educ. Couns. PD APR PY 2012 VL 87 IS 1 BP 81 EP 92 DI 10.1016/j.pec.2011.07.024 PG 12 WC Public, Environmental & Occupational Health; Social Sciences, Interdisciplinary SC Public, Environmental & Occupational Health; Social Sciences - Other Topics GA 930YX UT WOS:000303182000014 PM 21924576 ER PT J AU Beral, V Hermon, C Peto, R Reeves, G Brinton, L Marchbanks, P Negri, E Ness, R Peeters, PHM Vessey, M Calle, EE Gapstur, SM Patel, AV Dal Maso, L Talamini, R Chetrit, A Hirsh-Yechezkel, G Lubin, F Sadetzki, S Allen, N Bull, D Callaghan, K Crossley, B Gaitskell, K Goodill, A Green, J Key, T Moser, K Collins, R Doll, R Gonzalez, CA Lee, N Ory, HW Peterson, HB Wingo, PA Martin, N Pardthaisong, T Silpisornkosol, S Theetranont, C Boosiri, B Chutivongse, S Jimakorn, P Virutamasen, P Wongsrichanalai, C Tjonneland, A Titus-Ernstoff, L Byers, T Rohan, T Mosgaard, BJ Yeates, D Freudenheim, JL Chang-Claude, J Kaaks, R Anderson, KE Folsom, A Robien, K Rossing, MA Thomas, DB Weiss, NS Riboli, E Clavel-Chapelon, F Cramer, D Hankinson, SE Tworoger, SS Franceschi, S La Vecchia, C Magnusson, C Riman, T Weiderpass, E Wolk, A Schouten, LJ van den Brandt, PA Chantarakul, N Koetsawang, S Rachawat, D Palli, D Black, A de Gonzalez, AB Freedman, DM Hartge, P Hsing, AW Lacey, JV Hoover, RN Schairer, C Graff-Iversen, S Selmer, R Bain, CJ Green, AC Purdie, DM Siskind, V Webb, PM McCann, SE Hannaford, P Kay, C Binns, CW Lee, AH Zhang, M Ness, RB Nasca, P Coogan, PF Palmer, JR Rosenberg, L Kelsey, J Paffenbarger, R Whittemore, A Katsouyanni, K Trichopoulou, A Trichopoulos, D Tzonou, A Dabancens, A Martinez, L Molina, R Salas, O Goodman, MT Lurie, G Carney, ME Wilkens, LR Hartman, L Manjer, J Olsson, H Grisso, JA Morgan, M Wheeler, JE Casagrande, J Pike, MC Ross, RK Wu, AH Miller, AB Kumle, M Lund, E McGowan, L Shu, XO Zheng, W Farley, TMM Holck, S Meirik, O Risch, HA AF Beral, V. Hermon, C. Peto, R. Reeves, G. Brinton, L. Marchbanks, P. Negri, E. Ness, R. Peeters, P. H. M. Vessey, M. Calle, E. E. Gapstur, S. M. Patel, A. V. Dal Maso, L. Talamini, R. Chetrit, A. Hirsh-Yechezkel, G. Lubin, F. Sadetzki, S. Allen, N. Bull, D. Callaghan, K. Crossley, B. Gaitskell, K. Goodill, A. Green, J. Key, T. Moser, K. Collins, R. Doll, R. Gonzalez, C. A. Lee, N. Ory, H. W. Peterson, H. B. Wingo, P. A. Martin, N. Pardthaisong, T. Silpisornkosol, S. Theetranont, C. Boosiri, B. Chutivongse, S. Jimakorn, P. Virutamasen, P. Wongsrichanalai, C. Tjonneland, A. Titus-Ernstoff, L. Byers, T. Rohan, T. Mosgaard, B. J. Yeates, D. Freudenheim, J. L. Chang-Claude, J. Kaaks, R. Anderson, K. E. Folsom, A. Robien, K. Rossing, M. A. Thomas, D. B. Weiss, N. S. Riboli, E. Clavel-Chapelon, F. Cramer, D. Hankinson, S. E. Tworoger, S. S. Franceschi, S. La Vecchia, C. Magnusson, C. Riman, T. Weiderpass, E. Wolk, A. Schouten, L. J. van den Brandt, P. A. Chantarakul, N. Koetsawang, S. Rachawat, D. Palli, D. Black, A. de Gonzalez, A. Berrington Freedman, D. M. Hartge, P. Hsing, A. W. Lacey, J. V., Jr. Hoover, R. N. Schairer, C. Graff-Iversen, S. Selmer, R. Bain, C. J. Green, A. C. Purdie, D. M. Siskind, V. Webb, P. M. McCann, S. E. Hannaford, P. Kay, C. Binns, C. W. Lee, A. H. Zhang, M. Ness, R. B. Nasca, P. Coogan, P. F. Palmer, J. R. Rosenberg, L. Kelsey, J. Paffenbarger, R. Whittemore, A. Katsouyanni, K. Trichopoulou, A. Trichopoulos, D. Tzonou, A. Dabancens, A. Martinez, L. Molina, R. Salas, O. Goodman, M. T. Lurie, G. Carney, M. E. Wilkens, L. R. Hartman, L. Manjer, J. Olsson, H. Grisso, J. A. Morgan, M. Wheeler, J. E. Casagrande, J. Pike, M. C. Ross, R. K. Wu, A. H. Miller, A. B. Kumle, M. Lund, E. McGowan, L. Shu, X. O. Zheng, W. Farley, T. M. M. Holck, S. Meirik, O. Risch, H. A. CA Collaborative Grp Epidemiol Studie TI Ovarian Cancer and Body Size: Individual Participant Meta-Analysis Including 25,157 Women with Ovarian Cancer from 47 Epidemiological Studies SO PLOS MEDICINE LA English DT Article ID ORAL-CONTRACEPTIVE USE; REQUIRING PROLONGED OBSERVATION; EPITHELIAL OVARIAN; MASS INDEX; ANTHROPOMETRIC MEASURES; PROSPECTIVE COHORT; UNITED-STATES; RISK-FACTORS; POSTMENOPAUSAL WOMEN; HORMONAL FACTORS AB Background: Only about half the studies that have collected information on the relevance of women's height and body mass index to their risk of developing ovarian cancer have published their results, and findings are inconsistent. Here, we bring together the worldwide evidence, published and unpublished, and describe these relationships. Methods and Findings: Individual data on 25,157 women with ovarian cancer and 81,311 women without ovarian cancer from 47 epidemiological studies were collected, checked, and analysed centrally. Adjusted relative risks of ovarian cancer were calculated, by height and by body mass index. Ovarian cancer risk increased significantly with height and with body mass index, except in studies using hospital controls. For other study designs, the relative risk of ovarian cancer per 5 cm increase in height was 1.07 (95% confidence interval [CI], 1.05-1.09; p<0.001); this relationship did not vary significantly by women's age, year of birth, education, age at menarche, parity, menopausal status, smoking, alcohol consumption, having had a hysterectomy, having first degree relatives with ovarian or breast cancer, use of oral contraceptives, or use of menopausal hormone therapy. For body mass index, there was significant heterogeneity (p<0.001) in the findings between ever-users and never-users of menopausal hormone therapy, but not by the 11 other factors listed above. The relative risk for ovarian cancer per 5 kg/m(2) increase in body mass index was 1.10 (95% CI, 1.07-1.13; p<0.001) in never-users and 0.95 (95% CI, 0.92-0.99; p = 0.02) in ever-users of hormone therapy. Conclusions: Ovarian cancer is associated with height and, among never-users of hormone therapy, with body mass index. In high-income countries, both height and body mass index have been increasing in birth cohorts now developing the disease. If all other relevant factors had remained constant, then these increases in height and weight would be associated with a 3% increase in ovarian cancer incidence per decade. C1 [Beral, V.; Hermon, C.; Reeves, G.; Allen, N.; Bull, D.; Callaghan, K.; Crossley, B.; Gaitskell, K.; Goodill, A.; Green, J.; Key, T.; Moser, K.] Canc Epidemiol Unit, Oxford, England. [Calle, E. E.; Gapstur, S. M.; Patel, A. V.] Amer Canc Soc, Atlanta, GA 30329 USA. [Dal Maso, L.; Talamini, R.] Aviano Canc Ctr, Pordenone, Italy. [Chetrit, A.; Hirsh-Yechezkel, G.; Lubin, F.; Sadetzki, S.] Gertner Inst, Canc & Radiat Epidemiol Unit, Tel Hashomer, Israel. [Peto, R.; Collins, R.; Doll, R.] Canc Res UK MRC BHF Clin Trial Serv Unit, Oxford, England. [Peto, R.; Collins, R.; Doll, R.] Epidemiol Studies Unit, Oxford, England. [Gonzalez, C. A.] Catalan Inst Oncol, Barcelona, Spain. [Marchbanks, P.; Lee, N.; Ory, H. W.; Peterson, H. B.; Wingo, P. A.] Ctr Dis Control & Prevent, Atlanta, GA USA. [Martin, N.; Pardthaisong, T.; Silpisornkosol, S.; Theetranont, C.] Chiang Mai Univ, Chiang Mai 50000, Thailand. [Boosiri, B.; Chutivongse, S.; Jimakorn, P.; Virutamasen, P.; Wongsrichanalai, C.] Chulalongkorn Univ, Bangkok, Thailand. [Tjonneland, A.] Danish Canc Soc, Inst Canc Epidemiol, Copenhagen, Denmark. [Titus-Ernstoff, L.] Dartmouth Coll, Hitchcock Med Ctr, Dartmouth Med Sch, Hanover, NH 03756 USA. [Byers, T.] Colorado Sch Publ Hlth, Dept Epidemiol, Denver, CO USA. [Rohan, T.] Albert Einstein Coll Med, Dept Epidemiol & Populat Hlth, Bronx, NY 10467 USA. [Mosgaard, B. J.] Herlev Univ Hosp, Dept Obstet & Gynaecol, Copenhagen, Denmark. [Vessey, M.; Yeates, D.] Dept Publ Hlth, Oxford, England. [Freudenheim, J. L.] SUNY Buffalo, Dept Social & Prevent Med, Buffalo, NY 14260 USA. [Chang-Claude, J.; Kaaks, R.] German Canc Res Ctr, Div Canc Epidemiol, Heidelberg, Germany. [Anderson, K. E.; Folsom, A.; Robien, K.] Univ Minnesota, Sch Publ Hlth, Div Epidemiol, Minneapolis, MN 55455 USA. [Rossing, M. A.; Thomas, D. B.; Weiss, N. S.] Univ Washington, Fred Hutchinson Canc Res Ctr, Seattle, WA 98195 USA. [Riboli, E.] Univ London Imperial Coll Sci Technol & Med, London, England. [Clavel-Chapelon, F.] Paris S Univ, UMRS 1018, Inst Cancerol Gustave Roussy, Villejuif, France. [Clavel-Chapelon, F.] INSERM, U1018, Villejuif, France. [Cramer, D.] Harvard Univ, Sch Med, Brigham & Womens Hosp, Cambridge, MA 02138 USA. [Hankinson, S. E.; Tworoger, S. S.] Harvard Univ, Sch Med, Channing Lab Nurses Hlth Study, Cambridge, MA 02138 USA. [Franceschi, S.] Int Agcy Res Canc, F-69372 Lyon, France. [Negri, E.; La Vecchia, C.] Univ Milan, Ist Ric Farmacol Mario Negri, Milan, Italy. [Magnusson, C.; Riman, T.; Weiderpass, E.; Wolk, A.] Karolinska Inst, Stockholm, Sweden. [Schouten, L. J.; van den Brandt, P. A.] Maastricht Univ, Maastricht, Netherlands. [Chantarakul, N.; Koetsawang, S.; Rachawat, D.] Mahidol Univ, Bangkok 10700, Thailand. [Palli, D.] Canc Res & Prevent Inst, Mol & Nutr Epidemiol Unit, Florence, Italy. [Brinton, L.; Black, A.; de Gonzalez, A. Berrington; Freedman, D. M.; Hartge, P.; Hsing, A. W.; Lacey, J. V., Jr.; Hoover, R. N.; Schairer, C.] NCI, Bethesda, MD 20892 USA. [Graff-Iversen, S.; Selmer, R.] Norwegian Inst Publ Hlth, Oslo, Norway. [Bain, C. J.; Green, A. C.; Purdie, D. M.; Siskind, V.; Webb, P. M.] Queensland Inst Med Res, Brisbane, Qld 4006, Australia. [Bain, C. J.; Green, A. C.; Purdie, D. M.; Siskind, V.; Webb, P. M.] Univ Queensland, Brisbane, Qld 4072, Australia. [McCann, S. E.] Roswell Pk Canc Inst, Buffalo, NY 14263 USA. [Hannaford, P.; Kay, C.] Royal Coll Gen Practitioners Oral Contracept Stud, London, England. [Binns, C. W.; Lee, A. H.; Zhang, M.] Curtin Univ Technol, Sch Publ Hlth, Perth, WA, Australia. [Ness, R. B.] Univ Texas Houston, Sch Publ Hlth, Houston, TX USA. [Nasca, P.] Univ Massachusetts, Sch Publ Hlth & Hlth Sci, Boston, MA 02125 USA. [Coogan, P. F.; Palmer, J. R.; Rosenberg, L.] Boston Univ, Slone Epidemiol Ctr, Boston, MA 02215 USA. [Kelsey, J.; Paffenbarger, R.; Whittemore, A.] Stanford Univ, Stanford, CA 94305 USA. [Katsouyanni, K.; Trichopoulou, A.; Trichopoulos, D.; Tzonou, A.] Univ Athens, Sch Med, GR-11527 Athens, Greece. [Dabancens, A.; Martinez, L.; Molina, R.; Salas, O.] Univ Chile, Santiago, Chile. [Goodman, M. T.; Lurie, G.; Carney, M. E.; Wilkens, L. R.] Univ Hawaii, Honolulu, HI 96822 USA. [Hartman, L.; Manjer, J.; Olsson, H.] Univ Hosp, Lund, Sweden. [Grisso, J. A.; Morgan, M.; Wheeler, J. E.] Univ Penn, Philadelphia, PA 19104 USA. [Peeters, P. H. M.] Univ Med Ctr Utrecht, Utrecht, Netherlands. [Casagrande, J.; Pike, M. C.; Ross, R. K.; Wu, A. H.] Univ So Calif, Los Angeles, CA USA. [Miller, A. B.] Univ Toronto, Toronto, ON, Canada. [Kumle, M.; Lund, E.] Univ Tromso, Tromso, Norway. [McGowan, L.] George Washington Univ, Washington, DC USA. [Shu, X. O.; Zheng, W.] Vanderbilt Univ, Nashville, TN USA. [Farley, T. M. M.; Holck, S.; Meirik, O.] WHO, UNDP, UNFPA, World Bank Special Programme Res Dev & Res Traini, CH-1211 Geneva, Switzerland. [Risch, H. A.] Yale Univ, Sch Publ Hlth, New Haven, CT 06520 USA. RP Beral, V (reprint author), Canc Epidemiol Unit, Oxford, England. RI Schouten, Leo/G-3713-2012; Beral, Valerie/B-2979-2013; Binns, Colin/A-6012-2008; Negri, Eva/B-7244-2013; Webb, Penelope/D-5736-2013; Clavel-Chapelon, Francoise/G-6733-2014; Gonzalez, Carlos A/O-4651-2014; Brinton, Louise/G-7486-2015; Weiderpass, Elisabete/M-4029-2016; OI dal maso, luigino/0000-0001-6163-200X; La Vecchia, Carlo/0000-0003-1441-897X; PALLI, Domenico/0000-0002-5558-2437; Robien, Kim/0000-0002-2120-2280; Negri, Eva/0000-0001-9712-8526; Webb, Penelope/0000-0003-0733-5930; Gonzalez, Carlos A/0000-0003-2822-9715; Brinton, Louise/0000-0003-3853-8562; Weiderpass, Elisabete/0000-0003-2237-0128; Tworoger, Shelley/0000-0002-6986-7046; Magnusson, Cecilia/0000-0002-8567-6725 FU Cancer Research UK FX Funding for this collaborative reanalyis of original data was provided by Cancer Research UK. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 66 TC 5 Z9 5 U1 0 U2 10 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 185 BERRY ST, STE 1300, SAN FRANCISCO, CA 94107 USA SN 1549-1277 J9 PLOS MED JI PLos Med. PD APR PY 2012 VL 9 IS 4 AR e1001200 DI 10.1371/journal.pmed.1001200 PG 12 WC Medicine, General & Internal SC General & Internal Medicine GA 933VZ UT WOS:000303393800003 ER PT J AU Krishna, MC Matsumoto, S Yasui, H Saito, K Devasahayam, N Subramanian, S Mitchell, JB AF Krishna, Murali C. Matsumoto, Shingo Yasui, Hironobu Saito, Keita Devasahayam, Nallathamby Subramanian, Sankaran Mitchell, James B. TI Electron Paramagnetic Resonance Imaging of Tumor pO(2) SO RADIATION RESEARCH LA English DT Article ID ALLOSTERIC HEMOGLOBIN MODIFIER; HYPOXIA-INDUCIBLE FACTOR-1; TISSUE OXYGEN-TENSION; TRANSIENT HYPOXIA; CANCER-THERAPY; MURINE TUMORS; BRAIN-TUMORS; SOLID TUMORS; EPR OXIMETRY; BLOOD-FLOW AB Electron paramagnetic resonance imaging (EPRI) can be used to noninvasively and quantitatively obtain three-dimensional maps of tumor PO,. The paramagnetic tracer triarylmethyl (TAM), a substituted trityl radical moiety, is not toxic to animals and provides narrow isotropic spectra, which is ideal for in vivo EPR imaging experiments. From the oxygen-induced spectral broadening of TAM, pO(2) maps can be derived using EPRI. The instrumentation consists of an EPRI spectrometer and 7T magnetic resonance imaging (MRI) system both operating at a common radiofrequency of 300 MHz. Anatomic images obtained by MRI can be overlaid with pO(2) maps obtained from EPRI. With imaging times of less than 3 min, it was possible to monitor the dynamics of oxygen changes in tumor and distinguish chronically hypoxic regions from acutely hypoxic regions. In this article, the principles of pO(2) imaging with EPR and some relevant examples of tumor imaging are reviewed. (C) 2012 by Radiation Research Society C1 [Krishna, Murali C.; Matsumoto, Shingo; Yasui, Hironobu; Saito, Keita; Devasahayam, Nallathamby; Subramanian, Sankaran; Mitchell, James B.] NCI, Radiat Biol Branch, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. RP Krishna, MC (reprint author), NCI, Radiat Biol Branch, Ctr Canc Res, NIH, Bldg 10,Room B3-B69,9000 Rockville Pike, Bethesda, MD 20892 USA. EM murali@helix.nih.gov FU Center for Cancer Research, National Cancer Institute, NIH FX This research was supported by the Intramural Research Program of the Center for Cancer Research, National Cancer Institute, NIH. NR 59 TC 16 Z9 16 U1 3 U2 21 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 APR PY 2012 VL 177 IS 4 SI SI BP 376 EP 386 DI 10.1667/RR2622.1 PG 11 WC Biology; Biophysics; Radiology, Nuclear Medicine & Medical Imaging SC Life Sciences & Biomedicine - Other Topics; Biophysics; Radiology, Nuclear Medicine & Medical Imaging GA 929WZ UT WOS:000303097700005 PM 22332927 ER PT J AU Marotta, F Kumari, A Catanzaro, R Solimene, U Jain, S Minelli, E Harada, M AF Marotta, Francesco Kumari, Archana Catanzaro, Roberto Solimene, Umberto Jain, Shalini Minelli, Emilio Harada, Masatoshi TI A Phytochemical Approach to Experimental Metabolic Syndrome-Associated Renal Damage and Oxidative Stress SO REJUVENATION RESEARCH LA English DT Article ID CARDIOVASCULAR-DISEASE; KIDNEY-DISEASE; FRUCTOSE; HYPERTENSION; NOTOGINSENG; MORTALITY; EXTRACTS; ADULTS; RATS AB The aim of this study was to evaluate the effect of DTS-phytocompound on oxidant-antioxidant balance and protein damage in the kidneys of rats administered high doses of fructose. Adult male Wistar rats were divided into four groups. Group A received a control diet, whereas groups B and C were fed a high-fructose diet (60 g/100 g), the latter with additional DTS (50 mg/kg per day) for 60 days. Lipo-and nitro-peroxidation together with alpha-smooth muscle actin (alpha-SMA) expression in the glomerular and interstitial tissue of the kidneys were measured after 60 days. Fructose-fed rats showed significantly higher lipoperoxidation, 2,4-dinitrophenol and 3-nitrotyrosine protein adducts, and upregulation of alpha-SMA in the kidney. DTS significantly decreased such redox unbalance in renal tissue, while partially downregulating alpha-SMA (p < 0.01). These data suggest the potential clinical benefit of DTS in protecting the kidneys from metabolic syndrome-associated changes; gender-related analysis is under way. C1 [Marotta, Francesco] ReGenera Res Grp Aging Intervent, I-20154 Milan, Italy. [Kumari, Archana] Univ Quebec, Inst Natl Rech Sci, Ctr Eau Terre & Environm, Quebec City, PQ, Canada. [Catanzaro, Roberto] Univ Catania, Dept Internal Med, Gastroenterol Unit, Catania, Italy. [Solimene, Umberto; Minelli, Emilio] Univ Milan, WHO Ctr Biotechnol & Tradit Med, Milan, Italy. [Jain, Shalini] NIDDK, NIH, Bethesda, MD USA. [Harada, Masatoshi] MCH Hosp, Saitama, Japan. RP Marotta, F (reprint author), ReGenera Res Grp Aging Intervent, Piazza Firenze 12, I-20154 Milan, Italy. EM fmarchimede@libero.it NR 21 TC 0 Z9 0 U1 1 U2 3 PU MARY ANN LIEBERT INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1549-1684 J9 REJUV RES JI Rejuv. Res. PD APR PY 2012 VL 15 IS 2 BP 153 EP 156 DI 10.1089/rej.2011.1266 PG 4 WC Geriatrics & Gerontology SC Geriatrics & Gerontology GA 933SS UT WOS:000303383600010 PM 22533421 ER PT J AU Marotta, F Kumari, A Yadav, H Polimeni, A Soresi, V Lorenzetti, A Naito, Y Jain, S AF Marotta, Francesco Kumari, Archana Yadav, Hariom Polimeni, Ascanio Soresi, Vincenzo Lorenzetti, Aldo Naito, Yasuhiro Jain, Shalini TI Biomarine Extracts Significantly Protect from Ultraviolet A-Induced Skin Photoaging: An Ex Vivo Study SO REJUVENATION RESEARCH LA English DT Article ID MATRIX METALLOPROTEINASES; IN-VITRO; RADIATION; PURIFICATION; MECHANISMS AB We tested the activity of the marine nutraceutical CL-1222 added with a coenzyme Q10 (CoQ10)-lutein-selenium component (Celergen (R), Laboratoires-Dom, Switzerland) to protect human fibroblasts against ultraviolet A (UVA)-induced photoaging. Cells obtained from 22- to 39-year-old healthy donors were pretreated with CL-1222 before UV irradiation, as compared with same quantity of the CoQ10-lutein-selenium component. As compared to untreated control, UVA-irradiated samples exhibited a significant increase of secreted matrix metalloproteinase-1 (MMP-1) (p < 0.001) with over four-fold MMP-1 upregulation (p < 0.001). Samples treated with CL-1222, but not with the CoQ10-lutein-selenium component, showed a significant decrease of MMP-1 secretion (p < 0.01) and expression decrease (> 60%, p < 0.01) with > 54% elastase activity inhibition (p < 0.01). This preliminary study shows that such marine nutraceuticals can significantly protect against UV-irradiation irrespective of the CoQ10-lutein-selenium component with a specific protective gene expression modulation amenable to novel clinical applications. C1 [Marotta, Francesco; Polimeni, Ascanio; Lorenzetti, Aldo] Regenera Res Grp Aging Intervent, I-20154 Milan, Italy. [Kumari, Archana] Univ Quebec, Inst Natl Rech Sci, Ctr Eau Terre & Environm, Quebec City, PQ, Canada. [Yadav, Hariom; Jain, Shalini] NIDDK, NIH, Bethesda, MD USA. [Soresi, Vincenzo] Octopus Sci Assoc Bioprevent, Milan, Italy. [Naito, Yasuhiro] Immunol Res Inst & Clin, Nagoya, Aichi, Japan. RP Marotta, F (reprint author), Regenera Res Grp Aging Intervent, Viazza Firenze 12, I-20154 Milan, Italy. EM fmarchimede@libero.it OI Yadav, Hariom/0000-0003-4504-1597 NR 16 TC 1 Z9 1 U1 0 U2 4 PU MARY ANN LIEBERT INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1549-1684 J9 REJUV RES JI Rejuv. Res. PD APR PY 2012 VL 15 IS 2 BP 157 EP 160 DI 10.1089/rej.2011.1267 PG 4 WC Geriatrics & Gerontology SC Geriatrics & Gerontology GA 933SS UT WOS:000303383600011 PM 22533422 ER PT J AU Marotta, F Polimeni, A Solimene, U Lorenzetti, A Minelli, E Jain, S Rastmanesh, R Sedriep, S Soresi, V AF Marotta, Francesco Polimeni, Ascanio Solimene, Umberto Lorenzetti, Aldo Minelli, Emilio Jain, Shalini Rastmanesh, Reza Sedriep, Sonia Soresi, Vincenzo TI Beneficial Modulation from a High-Purity Caviar-Derived Homogenate on Chronological Skin Aging SO REJUVENATION RESEARCH LA English DT Article ID OXIDATIVE STRESS; AGED SKIN; FIBROBLASTS; DISEASE; SALMON AB This study tested the activity of LD-1227, which contains a caviar-derived homogenate added with coenzyme Q(10) (CoQ(10))-selenium component (CaviarLieri (R), Lab-Dom, Switzerland), in aged human skin and its potential role on skin mitochondria function. Human dermal fibroblasts were obtained from healthy donors over 70 years old and treated with LD-1227 for 72 hr. As compared to baseline, LD-1227 caused a robust (> 67%) collagen type I synthesis (p < 0.001) and decreased fibronectin synthesis (p < 0.05) with significant fibronectin messenger RNA (mRNA) downregulation (p < 0.05, r = 0.78). A significant collagen mRNA overexpression occurred with LD-1227 treatment (p < 0.05). Mitochondria cytosolic adenosine triphosphate (ATP) level decreased in aged skin samples (p < 0.05 vs. young control), but this phenomenon was reversed by LD-1227 (p < 0.01). These data show that LD-1227 may modify the extracellular matrix milieu in aged skin and also beneficially affect mitochondrial function. C1 [Marotta, Francesco; Polimeni, Ascanio; Lorenzetti, Aldo; Sedriep, Sonia] ReGenera Res Grp Aging Intervent, I-20154 Milan, Italy. [Solimene, Umberto; Minelli, Emilio] Univ Milan, WHO Ctr Biotechnol & Tradit Med, Milan, Italy. [Jain, Shalini] NIDDK, NIH, Bethesda, MD USA. [Rastmanesh, Reza] Shahid Beheshti Univ Med Sci, Fac Nutr Sci & Food Technol, Dept Clin Nutr & Dietet, Natl Nutr & Food Technol Res Inst, Tehran, Iran. [Soresi, Vincenzo] Octopus Sci Assoc Bioprevent, Milan, Italy. RP Marotta, F (reprint author), ReGenera Res Grp Aging Intervent, Piazza Firenze 12, I-20154 Milan, Italy. EM fmarchimede@libero.it NR 20 TC 2 Z9 2 U1 0 U2 6 PU MARY ANN LIEBERT INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1549-1684 J9 REJUV RES JI Rejuv. Res. PD APR PY 2012 VL 15 IS 2 BP 174 EP 177 DI 10.1089/rej.2011.1274 PG 4 WC Geriatrics & Gerontology SC Geriatrics & Gerontology GA 933SS UT WOS:000303383600015 PM 22533426 ER PT J AU Marotta, F Yadav, H Kumari, A Catanzaro, R Jain, S Polimeni, A Lorenzetti, A Soresi, V AF Marotta, Francesco Yadav, Hariom Kumari, Archana Catanzaro, Roberto Jain, Shalini Polimeni, Ascanio Lorenzetti, Aldo Soresi, Vincenzo TI Cardioprotective Effect of a Biofermented Nutraceutical on Endothelial Function in Healthy Middle-Aged Subjects SO REJUVENATION RESEARCH LA English DT Article ID FERMENTED PAPAYA PREPARATION; ASYMMETRIC DIMETHYLARGININE; DYSFUNCTION; ATHEROSCLEROSIS; MACROPHAGES AB We tested a biofermented nutraceutical (FPP) that has been previously shown to positively modulate nitric oxide (NO). Forty-two healthy middle-aged subjects were given 3 grams of FPP three times a day for 6 weeks, and tests were repeated at 3 and 6 weeks; the control group was given a placebo. Flow-mediated dilation (FMD) was measured together with NO compounds (nitrogen oxides [NOx]: NO2- + NO3-) plasma levels and asymmetrical dimethylarginine (ADMA). In the interventional group, overall FMD significantly increased from 4.2% to 7.3% (p < 0.05 vs. placebo). A significant increase in plasma NO and a decrease in ADMA were detected after consumption of FPP (p < 0.01). Although larger studies are awaited, it appears that, at least in healthy individuals, such nutraceutical intervention by positively acting on significant cardiovascular parameters can be considered in the armamentarium of a proactive age-management strategy. C1 [Marotta, Francesco; Polimeni, Ascanio; Lorenzetti, Aldo] ReGenera Res Grp Aging Intervent, I-20154 Milan, Italy. [Yadav, Hariom; Jain, Shalini] NIDDK, NIH, Bethesda, MD USA. [Kumari, Archana] Univ Quebec, Inst Natl Rech Sci, Ctr Eau Terre & Environm, Quebec City, PQ, Canada. [Catanzaro, Roberto] Univ Catania, Dept Internal Med, Gastroenterol Unit, Catania, Italy. [Soresi, Vincenzo] Octopus Sci Assoc Bioprevent, Milan, Italy. RP Marotta, F (reprint author), ReGenera Res Grp Aging Intervent, Piazza Firenze 12, I-20154 Milan, Italy. EM fmarchimede@libero.it OI Yadav, Hariom/0000-0003-4504-1597 NR 21 TC 3 Z9 3 U1 0 U2 2 PU MARY ANN LIEBERT INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1549-1684 J9 REJUV RES JI Rejuv. Res. PD APR PY 2012 VL 15 IS 2 BP 178 EP 181 DI 10.1089/rej.2011.1276 PG 4 WC Geriatrics & Gerontology SC Geriatrics & Gerontology GA 933SS UT WOS:000303383600016 PM 22533427 ER PT J AU Sempos, CT Vesper, HW Phinney, KW Thienpont, LM Coates, PM AF Sempos, Christopher T. Vesper, Hubert W. Phinney, Karen W. Thienpont, Linda M. Coates, Paul M. CA VDSP TI Vitamin D status as an international issue: National surveys and the problem of standardization SO SCANDINAVIAN JOURNAL OF CLINICAL & LABORATORY INVESTIGATION LA English DT Article DE 25-hydroxyvitamin D; 3-epi-25-hydroxyvitamin D; Calibration; Commutability; CAP; DEQAS; Harmonization; NIST; CLSI; Standardization; Traceability ID TANDEM MASS-SPECTROMETRY; 25-HYDROXYVITAMIN D-3; HUMAN SERUM; ADULTS AB Wide spread variation in measurement results of total 25-hydroxyvitamin D (25(OH)D) confounds international efforts to develop evidence-based clinical guidelines. Accordingly, NIH Office of Dietary Supplements (ODS) in collaboration with CDC National Center for Environmental Health (NCEH), National Institute of Standards and Technology (NIST) and Ghent University established the Vitamin D Standardization Program (VDSP) in November 2010. VDSP objectives include: (1) standardize 25(OH)D concentration measurements in national health surveys around the world, (2) evaluate survey differences, (3) extend standardization efforts to assay manufacturers, and to clinical, commercial, and research laboratories, (4) promote standardization of emerging metabolites of vitamin D status, and (5) enable the use of standardized data in patient care and public health. An interlaboratory comparison study is being conducted to assess measurement variability among current assays. Participants include national health surveys from Australia, Canada, Germany, Ireland, Mexico, South Korea, UK and USA, 15 assay manufacturers, and two external quality assurance programs. CDC will implement a formal laboratory certification program. Standardization activities will use single-donor, fresh-frozen serum collected using the CLSI C37 protocol. Initial assay performance criteria, based on biological variability data, are <= 10 % imprecision and <= 5 % bias in relation to the reference values. An ancillary study on commutability of NIST SRM 972a, external quality assurance testing materials is included. To increase the comparability of existing data from different national surveys, master equations will be developed to facilitate the conversion of already existing national survey data to the NIST-Ghent University reference measurement procedures. C1 [Sempos, Christopher T.; Coates, Paul M.] NIH, Off Dietary Supplements, Bethesda, MD 20892 USA. [Vesper, Hubert W.] Ctr Dis Control & Prevent, Natl Ctr Environm Hlth, Atlanta, GA USA. [Phinney, Karen W.] Natl Inst Stand & Technol, Div Analyt Chem, Gaithersburg, MD 20899 USA. [Thienpont, Linda M.] Univ Ghent, Fac Pharmaceut Sci, Analyt Chem Lab, B-9000 Ghent, Belgium. RP Sempos, CT (reprint author), NIH, Off Dietary Supplements, 6100 Execut Blvd,Rm 3B01, Bethesda, MD 20892 USA. EM semposch@mail.nih.gov; hvesper@cdc.gov RI Mensink, Gert/B-2447-2009; OI Mensink, Gert/0000-0001-6268-5998; Young, Ian/0000-0003-3890-3152; Van Uytfanghe, Katleen/0000-0001-8195-150X; Flynn, Albert/0000-0002-7072-4202 FU Medical Research Council [MC_U105960371, MC_U105960384] NR 28 TC 82 Z9 82 U1 0 U2 11 PU INFORMA HEALTHCARE PI LONDON PA TELEPHONE HOUSE, 69-77 PAUL STREET, LONDON EC2A 4LQ, ENGLAND SN 0036-5513 J9 SCAND J CLIN LAB INV JI Scand. J. Clin. Lab. Invest. PD APR PY 2012 VL 72 SU 243 BP 32 EP 40 DI 10.3109/00365513.2012.681935 PG 9 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 931VV UT WOS:000303248300006 PM 22536760 ER PT J AU Lee, YS Simeon, FG Briard, E Pike, VW AF Lee, Yong-Sok Simeon, Fabrice G. Briard, Emmanuelle Pike, Victor W. TI Solution Structures of the Prototypical 18 kDa Translocator Protein Ligand, PK 11195, Elucidated with H-1/C-13 NMR Spectroscopy and Quantum Chemistry SO ACS CHEMICAL NEUROSCIENCE LA English DT Article DE PK 11195; dynamic H-1/C-13 NMR; TSPO; rotamer; variable temperature; energetics; quantum chemistry; structure ID PERIPHERAL BENZODIAZEPINE-RECEPTOR; NUCLEAR-MAGNETIC-RESONANCE; BINDING-SITE; IN-VIVO; AMIDES; ROTATION; DERIVATIVES; BOND; N,N-DIMETHYLFORMAMIDE; NEUROINFLAMMATION AB Eighteen kilodalton translocator protein (TSPO) is an important target for drug discovery and for clinical molecular imaging of brain and peripheral inflammatory processes. PK 11195 [1a; 1-(2-chlorophenyl)-N-methyl-(1-methylpropyl)-3-isoquinoline carboxamide) is the major prototypical high-affinity ligand for TSPO. Elucidation of the solution structure of la is of interest for understanding small-molecule ligand interactions with the lipophilic binding site of TSPO. Dynamic H-1/C-13 NMR spectroscopy of 1a revealed four quite stable but interconverting rotamers, due to amide bond and 2-chlorophenyl group rotation. These rotamers have been neglected in previous descriptions of the structure of la and of the binding of 1a to TSPO. Here, we used quantum chemistry at the level of B3LYP/6-311+G(2d,p) to calculate C-13 and H-1 chemical shifts for the rotamers of 1a and for the very weak TSPO ligand, N-desmethyl-PK 11195 (1b). These data, plus experimental NMR data, were then used to characterize the structures of rotamers of 1a and 1b in organic solution. Energy barriers for both the amide bond and 2'-chlorophenyl group rotation of 1a were determined from dynamic H-1 NMR to be similar (ca.17 to 18 kcal/mol), and they compared well with those calculated at the level of B3LYP/6-31G*. Furthermore, the computed barrier for Z to E rotation is considerably lower in 1a (18.7 kcal/mol) than in 1b (25.4 kcal/mol). NMR (NOE) unequivocally demonstrated that the E rotamer of 1a is the more stable in solution by about 0.4 kcal/mol. These detailed structural findings will aid future TSPO ligand design and support the notion that TSPO prefers to bind ligands as amide E-rotamers. C1 [Simeon, Fabrice G.; Briard, Emmanuelle; Pike, Victor W.] NIMH, PET Radiopharmaceut Sci Sect, Mol Imaging Branch, NIH, Bethesda, MD 20892 USA. [Lee, Yong-Sok] NIH, Ctr Mol Modeling, Div Computat Biosci, Ctr Informat Technol, Bethesda, MD 20892 USA. RP Pike, VW (reprint author), NIMH, PET Radiopharmaceut Sci Sect, Mol Imaging Branch, NIH, Bldg 10,Room B3 C346A,10 Ctr Dr, Bethesda, MD 20892 USA. EM pikev@mail.nih.gov FU National Institutes of Health (CIT); National Institutes of Health (NIMH) FX This research was supported by the Intramural Research Program of the National Institutes of Health (CIT and NIMH). NR 50 TC 8 Z9 8 U1 2 U2 8 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 1948-7193 J9 ACS CHEM NEUROSCI JI ACS Chem. Neurosci. PD APR PY 2012 VL 3 IS 4 BP 325 EP 335 DI 10.1021/cn3000108 PG 11 WC Biochemistry & Molecular Biology; Chemistry, Medicinal; Neurosciences SC Biochemistry & Molecular Biology; Pharmacology & Pharmacy; Neurosciences & Neurology GA 927BH UT WOS:000302881400010 PM 22860199 ER PT J AU Algin, O Turkbey, B AF Algin, O. Turkbey, B. TI Evaluation of Aqueductal Stenosis by 3D Sampling Perfection with Application-Optimized Contrasts Using Different Flip Angle Evolutions Sequence: Preliminary Results with 3T MR Imaging SO AMERICAN JOURNAL OF NEURORADIOLOGY LA English DT Article ID CISTERNOGRAPHY; 3D-CISS AB BACKGROUND AND PURPOSE: Diagnosis of AS and periaqueductal abnormalities by routine MR imaging sequences is challenging for neuroradiologists. The aim of our study was to evaluate the utility of the 3D-SPACE sequence with VFAM in patients with suspected AS. MATERIALS AND METHODS: PC-MRI and 3D-SPACE images were obtained in 21 patients who had hydrocephalus on routine MR imaging scans and had clinical suspicion of AS, as well as in 12 control subjects. Aqueductal patency was visually scored (grade 0, normal; grade 1, partial obstruction; grade 2, complete stenosis) by 2 experienced radiologists on PC-MRI (plus routine T1-weighted and T2-weighted images) and 3D-SPACE images. Two separate scores were statistically compared with each other as well as with the consensus scores obtained from general agreement of both radiologists. RESULTS: There was an excellent correlation between 3D-SPACE and PC-MRI scores (kappa = 0.828). The correlation between 3D-SPACE scorings and consensus-based scorings was higher compared with the correlation between PC-MRI and consensus-based scorings (r = 1, P < .001 and r = 0.966, P < .001, respectively). CONCLUSIONS: 3D-SPACE sequence with VFAM alone can be used for adequate and successful evaluation of the aqueductal patency without the need for additional sequences and examinations. Noninvasive evaluation of the whole cranium is possible in a short time with high resolution by using 3D-SPACE. C1 [Algin, O.] Ataturk Training & Res Hosp, Dept Radiol, Ankara, Turkey. [Turkbey, B.] NCI, NIH, Bethesda, MD USA. RP Algin, O (reprint author), Ataturk Training & Res Hosp, Dept Radiol, Ankara, Turkey. EM droktayalgin@gmail.com NR 20 TC 16 Z9 16 U1 1 U2 4 PU AMER SOC NEURORADIOLOGY PI OAK BROOK PA 2210 MIDWEST RD, OAK BROOK, IL 60521 USA SN 0195-6108 J9 AM J NEURORADIOL JI Am. J. Neuroradiol. PD APR PY 2012 VL 33 IS 4 BP 740 EP 746 DI 10.3174/ajnr.A2833 PG 7 WC Clinical Neurology; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA 926PI UT WOS:000302842900027 PM 22173764 ER PT J AU Lizunov, VA Stenkula, KG Lisinski, I Gavrilova, O Yver, DR Chadt, A Al-Hasani, H Zimmerberg, J Cushman, SW AF Lizunov, Vladimir A. Stenkula, Karin G. Lisinski, Ivonne Gavrilova, Oksana Yver, Dena R. Chadt, Alexandra Al-Hasani, Hadi Zimmerberg, Joshua Cushman, Samuel W. TI Insulin stimulates fusion, but not tethering, of GLUT4 vesicles in skeletal muscle of HA-GLUT4-GFP transgenic mice SO AMERICAN JOURNAL OF PHYSIOLOGY-ENDOCRINOLOGY AND METABOLISM LA English DT Article DE hemagglutinin; glucose transporter 4; green fluorescent protein; insulin; fusion ID GTPASE-ACTIVATING-PROTEIN; RAT ADIPOSE-CELLS; LIVING MICE; GLUCOSE TRANSPORTERS; PLASMA-MEMBRANE; TRANSLOCATION; TRAFFICKING; FIBERS; AS160; CONTRACTION AB Insulin stimulates fusion, but not tethering, of GLUT4 vesicles in skeletal muscle of HA-GLUT4-GFP transgenic mice. Am J Physiol Endocrinol Metab 302: E950-E960, 2012. First published January 31, 2012; doi:10.1152/ajpendo.00466.2011.-Insulin regulates glucose uptake into fat and muscle by modulating the subcellular distribution of GLUT4 between the cell surface and intracellular compartments. However, quantification of these translocation processes in muscle by classical subcellular fractionation techniques is confounded by contaminating microfibrillar protein; dynamic studies at the molecular level are almost impossible. In this study, we introduce a muscle-specific transgenic mouse model in which HA-GLUT4-GFP is expressed under the control of the MCK promoter. HA-GLUT4-GFP was found to translocate to the plasma membrane and T-tubules after insulin stimulation, thus mimicking endogenous GLUT4. To investigate the dynamics of GLUT4 trafficking in skeletal muscle, we quantified vesicles containing HA-GLUT4-GFP near the sarcolemma and T-tubules and analyzed insulin-stimulated exocytosis at the single vesicle level by total internal reflection fluorescence and confocal microscopy. We found that only 10% of the intracellular GLUT4 pool comprised mobile vesicles, whereas most of the GLUT4 structures remained stationary or tethered at the sarcolemma or T-tubules. In fact, most of the insulin-stimulated exocytosis emanated from pretethered vesicles, whereas the small pool of mobile GLUT4 vesicles was not significantly affected by insulin. Our data strongly suggest that the mobile pool of GLUT4 vesicles is not a major site of insulin action but rather locally distributed. Most likely, pretethered GLUT4 structures are responsible for the initial phase of insulin-stimulated exocytosis. C1 [Stenkula, Karin G.; Lisinski, Ivonne; Yver, Dena R.; Cushman, Samuel W.] NIDDK, Expt Diabet Metab & Nutr Sect, Diabet Endocrinol & Obes Branch, NIH, Bethesda, MD 20892 USA. [Gavrilova, Oksana] NIDDK, Mouse Metab Core Lab, NIH, Bethesda, MD USA. [Stenkula, Karin G.] Lund Univ, Lund, Sweden. [Lizunov, Vladimir A.; Zimmerberg, Joshua] NICHHD, Program Phys Biol, NIH, Bethesda, MD 20892 USA. [Chadt, Alexandra; Al-Hasani, Hadi] German Inst Human Nutr, Potsdam, Germany. [Al-Hasani, Hadi] Univ Dusseldorf, German Diabet Ctr, D-40225 Dusseldorf, Germany. RP Cushman, SW (reprint author), NIDDK, Expt Diabet Metab & Nutr Sect, Diabet Endocrinol & Obes Branch, NIH, Bethesda, MD 20892 USA. EM samc@mail.nih.gov FU Swedish Research Council; National Institute of Diabetes and Digestive and Kidney Diseases; National Institute of Child Health and Human Development, National Institutes of Health FX This work was supported in part by a Postdoctoral Fellowship to K. Stenkula from the Swedish Research Council and by the intramural research programs of National Institute of Diabetes and Digestive and Kidney Diseases and National Institute of Child Health and Human Development, National Institutes of Health. NR 37 TC 13 Z9 14 U1 0 U2 4 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0193-1849 J9 AM J PHYSIOL-ENDOC M JI Am. J. Physiol.-Endocrinol. Metab. PD APR PY 2012 VL 302 IS 8 BP E950 EP E960 DI 10.1152/ajpendo.00466.2011 PG 11 WC Endocrinology & Metabolism; Physiology SC Endocrinology & Metabolism; Physiology GA 924ZU UT WOS:000302730600006 PM 22297303 ER PT J AU Tahlan, K Wilson, R Kastrinsky, DB Arora, K Nair, V Fischer, E Barnes, SW Walker, JR Alland, D Barry, CE Boshoff, HI AF Tahlan, Kapil Wilson, Regina Kastrinsky, David B. Arora, Kriti Nair, Vinod Fischer, Elizabeth Barnes, S. Whitney Walker, John R. Alland, David Barry, Clifton E., III Boshoff, Helena I. TI SQ109 Targets MmpL3, a Membrane Transporter of Trehalose Monomycolate Involved in Mycolic Acid Donation to the Cell Wall Core of Mycobacterium tuberculosis SO ANTIMICROBIAL AGENTS AND CHEMOTHERAPY LA English DT Article ID DRUG DISCOVERY; ISONIAZID RESISTANCE; OUTER-MEMBRANE; IN-VITRO; ETHAMBUTOL; BIOSYNTHESIS; BIOGENESIS; ENVELOPE; ARABINOGALACTAN; IDENTIFICATION AB SQ109, a 1,2-diamine related to ethambutol, is currently in clinical trials for the treatment of tuberculosis, but its mode of action remains unclear. Here, we demonstrate that SQ109 disrupts cell wall assembly, as evidenced by macromolecular incorporation assays and ultrastructural analyses. SQ109 interferes with the assembly of mycolic acids into the cell wall core of Mycobacterium tuberculosis, as bacilli exposed to SQ109 show immediate inhibition of trehalose dimycolate (TDM) production and fail to attach mycolates to the cell wall arabinogalactan. These effects were not due to inhibition of mycolate synthesis, since total mycolate levels were unaffected, but instead resulted in the accumulation of trehalose monomycolate (TMM), the precursor of TDM and cell wall mycolates. In vitro assays using purified enzymes showed that this was not due to inhibition of the secreted Ag85 mycolyltransferases. We were unable to achieve spontaneous generation of SQ109-resistant mutants; however, analogs of this compound that resulted in similar shutdown of TDM synthesis with concomitant TMM accumulation were used to spontaneously generate resistant mutants that were also cross-resistant to SQ109. Whole-genome sequencing of these mutants showed that these all had mutations in the essential mmpL3 gene, which encodes a transmembrane transporter. Our results suggest that MmpL3 is the target of SQ109 and that MmpL3 is a transporter of mycobacterial TMM. C1 [Tahlan, Kapil; Kastrinsky, David B.; Arora, Kriti; Barry, Clifton E., III; Boshoff, Helena I.] NIAID, TB Res Sect, Lab Clin Infect Dis, NIH, Bethesda, MD 20892 USA. [Wilson, Regina; Alland, David] Univ Med & Dent New Jersey, New Jersey Med Sch, Dept Med, Div Infect Dis, Newark, NJ 07103 USA. [Wilson, Regina; Alland, David] Univ Med & Dent New Jersey, New Jersey Med Sch, Ruy V Lourenco Ctr Study Emerging & Reemerging Pa, Newark, NJ 07103 USA. [Nair, Vinod; Fischer, Elizabeth] NIAID, Res Technol Branch, Rocky Mt Labs, NIH, Hamilton, MT 59840 USA. [Barnes, S. Whitney; Walker, John R.] Novartis Res Fdn, Genom Inst, San Diego, CA USA. RP Boshoff, HI (reprint author), NIAID, TB Res Sect, Lab Clin Infect Dis, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA. EM hboshoff@niaid.nih.gov RI Barry, III, Clifton/H-3839-2012 FU NIAID; NIH; UNCF/Merck FX This study was funded (in part) by the Intramural Research Program of NIAID, NIH (to C.E.B.), and in part by a UNCF/Merck Postdoctoral Science Research Fellowship (to R.W.). NR 74 TC 156 Z9 161 U1 4 U2 43 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0066-4804 J9 ANTIMICROB AGENTS CH JI Antimicrob. Agents Chemother. PD APR PY 2012 VL 56 IS 4 BP 1797 EP 1809 DI 10.1128/AAC.05708-11 PG 13 WC Microbiology; Pharmacology & Pharmacy SC Microbiology; Pharmacology & Pharmacy GA 913SU UT WOS:000301898500017 PM 22252828 ER PT J AU Becker, KG AF Becker, Kevin G. TI Male Gender Bias in Autism and Pediatric Autoimmunity SO AUTISM RESEARCH LA English DT Review DE autoimmune; immunology; molecular genetics; pediatrics; developmental neurobiology ID REGULATORY T-CELLS; SPECTRUM DISORDERS; MULTIPLE-SCLEROSIS; SEX-DIFFERENCES; LEUKOTRIENE BIOSYNTHESIS; FAMILIAL AUTOIMMUNITY; INCREASED PREVALENCE; DIABETES-MELLITUS; PUBERTAL STAGE; X-CHROMOSOME AB Male bias in both autism and pediatric autoimmune disease is thought to involve hormonal perturbations in pregnancy or early childhood in the context of genetic control. These early molecular events, at a time of rapid development, are intimately linked to concurrent development in the brain and immune system. It is suggested here that these early regulatory events may overlap between autism and autoimmunity in determining male sex bias and may provide evidence of an etiological link among autism, immune dysregulation, and autoimmune disease. Autism Res 2012,:. Published 2012 International Society for Autism Research, Wiley Periodicals, Inc.dagger C1 NIA, Biomed Res Ctr, NIH, Gene Express & Genom Unit, Baltimore, MD 21224 USA. RP Becker, KG (reprint author), NIA, Biomed Res Ctr, NIH, Gene Express & Genom Unit, Suite 100,Room 4B122,251 Bayview Blvd, Baltimore, MD 21224 USA. EM beckerk@grc.nia.nih.gov OI Becker, Kevin/0000-0002-6794-6656 FU NIH, National Institute on Aging FX The author would like to thank Drs. Andrea Wurster, Larry Brant, and Bronwen Martin for helpful comments in editing the manuscript. This research was supported entirely by the Intramural Research Program of the NIH, National Institute on Aging. NR 101 TC 3 Z9 3 U1 4 U2 19 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1939-3792 J9 AUTISM RES JI Autism Res. PD APR PY 2012 VL 5 IS 2 BP 77 EP 83 DI 10.1002/aur.1227 PG 7 WC Behavioral Sciences; Psychology, Developmental SC Behavioral Sciences; Psychology GA 927KK UT WOS:000302906100001 PM 22431266 ER PT J AU Raznahan, A Lee, Y Vaituzis, C Tran, L Mackie, S Tiemeier, H Clasen, L Lalonde, F Greenstein, D Pierson, R Giedd, JN AF Raznahan, Armin Lee, Yohan Vaituzis, Catherine Tran, Lan Mackie, Susan Tiemeier, Henning Clasen, Liv Lalonde, Francois Greenstein, Dede Pierson, Ron Giedd, Jay N. TI Allelic Variation Within the Putative Autism Spectrum Disorder Risk Gene Homeobox A1 and Cerebellar Maturation in Typically Developing Children and Adolescents SO AUTISM RESEARCH LA English DT Article DE autism; HOXA1; cerebellum; gene; brain; MRI ID HOXA1 A218G POLYMORPHISM; BRAIN-STEM; CORTICAL DEVELOPMENT; INFANTILE-AUTISM; CELL-DEATH; ASSOCIATION; VARIANTS; MR; GROWTH; HOXB1 AB Homeobox A1 (HOXA1) has been proposed as a candidate gene for autism spectrum disorder (ASD) as it regulates embryological patterning of hind-brain structures implicated in autism neurobiology. In line with this notion, a nonsynonymous single nucleotide polymorphism within a highly conserved domain of HOXA1A218G (rs10951154)has been linked to both ASD risk, and cross-sectional differences in superior posterior lobar cerebellar anatomy in late adulthood. Despite evidence for early onset and developmentally dynamic cerebellar involvement in ASD, little is known of the relationship between A218G genotype and maturation of the cerebellum over early development. We addressed this issue using 296 longitudinally acquired structural magnetic resonance imaging brain scans from 116 healthy individuals between 5 and 23 years of age. Mixed models were used to compare the relationship between age and semi-automated measures of cerebellar volume in A-homozygotes (AA) and carriers of the G allele (Gcar). Total cerebellar volume increased between ages of 5 and 23 years in both groups. However, this was accelerated in the Gcar relative to the AA group (Genotype-by-age interaction term, P?=?0.03), and driven by genotype-dependent differences in the rate of bilateral superior posterior lobar volume change with age (P?=?0.002). Resultantly, although superior posterior lobar volume did not differ significantly between genotype groups at age 5 (P?=?0.9), by age 23 it was 12% greater in Gcar than AA (P?=?0.002). Our results suggest that common genetic variation within this putative ASD risk gene has the capacity to modify the development of cerebellar systems implicated in ASD neurobiology. C1 [Raznahan, Armin; Lee, Yohan; Vaituzis, Catherine; Tran, Lan; Mackie, Susan; Tiemeier, Henning; Clasen, Liv; Lalonde, Francois; Greenstein, Dede; Pierson, Ron; Giedd, Jay N.] NIMH, Child Psychiat Branch, NIH, Bethesda, MD 20892 USA. [Raznahan, Armin] Kings Coll London, Inst Psychiat, Child Psychiat Dept, London WC2R 2LS, England. RP Raznahan, A (reprint author), NIMH, Child Psychiat Branch, NIH, Bldg 10, Bethesda, MD 20892 USA. EM raznahana@mail.nih.gov RI Raznahan, Armin/F-4534-2012; Giedd, Jay/B-7302-2012; Giedd, Jay/J-9644-2015; OI Giedd, Jay/0000-0003-0827-3460; Giedd, Jay/0000-0003-2002-8978; Tiemeier, Henning/0000-0002-4395-1397 FU UK Medical Research Council [G0701370] FX A.R. was funded by the UK Medical Research Council Fellowship (G0701370) while carrying out aspects of this work. A.R. would like to thanks Professors Patrick Bolton, Declan Murphy, and Gareth Barker for their helpful comments on earlier versions of this article. NR 55 TC 7 Z9 7 U1 0 U2 6 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1939-3792 J9 AUTISM RES JI Autism Res. PD APR PY 2012 VL 5 IS 2 BP 93 EP 100 DI 10.1002/aur.238 PG 8 WC Behavioral Sciences; Psychology, Developmental SC Behavioral Sciences; Psychology GA 927KK UT WOS:000302906100003 PM 22359339 ER PT J AU Anderlini, P Tolar, J Deeg, H Arai, S Horwitz, M Antin, J McCarty, J Adams, R Ewell, M Leifer, E Gersten, I Carter, S Horowitz, M Confer, D Nakamura, R Pulsipher, M DiFronzo, N Eapen, M AF Anderlini, P. Tolar, J. Deeg, H. Arai, S. Horwitz, M. Antin, J. McCarty, J. Adams, R. Ewell, M. Leifer, E. Gersten, I. Carter, S. Horowitz, M. Confer, D. Nakamura, R. Pulsipher, M. DiFronzo, N. Eapen, M. TI Fludarabine-based conditioning for allogeneic marrow transplantation from unrelated donors in severe aplastic anaemia: serious and unexpected adverse events in pre-defined cyclophosphamide dose levels SO BONE MARROW TRANSPLANTATION LA English DT Meeting Abstract CT 38th Annual Meeting of the European-Group-for-Blood-and-Marrow-Transplantation (EBMT) CY APR 01-04, 2012 CL Geneva, SWITZERLAND SP European Grp Blood & Marrow Transplantat (EBMT) C1 [Anderlini, P.] UTMDACC, Houston, TX USA. [Tolar, J.] Univ Minnesota, Masonic Canc Ctr, Minneapolis, MN USA. [Deeg, H.] Fred Hutchinson Canc Res Ctr, Seattle, WA 98104 USA. [Arai, S.] Stanford Univ, Med Ctr, Stanford, CA 94305 USA. [Horwitz, M.] Duke Univ, Med Ctr, Durham, NC 27706 USA. [Antin, J.] Dana Farber Canc Inst, Boston, MA 02115 USA. [McCarty, J.] Virginia Commonwealth Univ Med Coll Virginia, Richmond, VA USA. [Adams, R.] Mayo Clin, Scottsdale, AZ USA. [Ewell, M.; Gersten, I.; Carter, S.] EMMES Corp, Rockville, MD USA. [Leifer, E.; DiFronzo, N.] NHLBI, Bethesda, MD 20892 USA. [Horowitz, M.; Eapen, M.] Med Coll Wisconsin, Milwaukee, WI 53226 USA. [Confer, D.] Natl Marrow Donor Program, Minneapolis, MN USA. [Pulsipher, M.] Univ Utah, Med Ctr, Salt Lake City, UT USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0268-3369 J9 BONE MARROW TRANSPL JI Bone Marrow Transplant. PD APR PY 2012 VL 47 SU 1 BP S219 EP S220 PG 2 WC Biophysics; Oncology; Hematology; Immunology; Transplantation SC Biophysics; Oncology; Hematology; Immunology; Transplantation GA 925GN UT WOS:000302749201275 ER PT J AU Barrett, J Ito, S Pophali, P Fahle, G Koklanaris, E Superata, J Childs, R Battiwalla, M AF Barrett, J. Ito, S. Pophali, P. Fahle, G. Koklanaris, E. Superata, J. Childs, R. Battiwalla, M. TI Cytomegalovirus reactivation is associated with a lower incidence of relapse after allogeneic stem cell transplantation for chronic myelogenous leukaemia SO BONE MARROW TRANSPLANTATION LA English DT Meeting Abstract CT 38th Annual Meeting of the European-Group-for-Blood-and-Marrow-Transplantation (EBMT) CY APR 01-04, 2012 CL Geneva, SWITZERLAND SP European Grp Blood & Marrow Transplantat (EBMT) C1 [Barrett, J.; Ito, S.; Pophali, P.; Koklanaris, E.; Superata, J.; Childs, R.; Battiwalla, M.] NHLBI, Bethesda, MD 20892 USA. [Fahle, G.] NIH, Bethesda, MD 20892 USA. RI Pophali, Priyanka/P-8646-2016 NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0268-3369 J9 BONE MARROW TRANSPL JI Bone Marrow Transplant. PD APR PY 2012 VL 47 SU 1 BP S427 EP S428 PG 2 WC Biophysics; Oncology; Hematology; Immunology; Transplantation SC Biophysics; Oncology; Hematology; Immunology; Transplantation GA 925GN UT WOS:000302749201699 ER PT J AU Barrett, J Pophali, P Battiwalla, M AF Barrett, J. Pophali, P. Battiwalla, M. TI Sustained increased risk of cardiovascular disease in the second decade post-transplant in male long-term survivors of allogeneic haematopoietic stem cell transplantation SO BONE MARROW TRANSPLANTATION LA English DT Meeting Abstract CT 38th Annual Meeting of the European-Group-for-Blood-and-Marrow-Transplantation (EBMT) CY APR 01-04, 2012 CL Geneva, SWITZERLAND SP European Grp Blood & Marrow Transplantat (EBMT) C1 [Barrett, J.; Pophali, P.; Battiwalla, M.] NHLBI, Bethesda, MD 20892 USA. RI Pophali, Priyanka/P-8646-2016 NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0268-3369 J9 BONE MARROW TRANSPL JI Bone Marrow Transplant. PD APR PY 2012 VL 47 SU 1 BP S54 EP S54 PG 1 WC Biophysics; Oncology; Hematology; Immunology; Transplantation SC Biophysics; Oncology; Hematology; Immunology; Transplantation GA 925GN UT WOS:000302749200116 ER PT J AU Bollard, C Cruz, C Savoldo, B Krance, R Kamble, R Barrett, A Hosing, C Shpall, E Heslop, H Leen, A Rooney, C Brenner, M Dotti, G AF Bollard, C. Cruz, C. Savoldo, B. Krance, R. Kamble, R. Barrett, A. Hosing, C. Shpall, E. Heslop, H. Leen, A. Rooney, C. Brenner, M. Dotti, G. TI Outcomes of CD19-directed multivirus specific cytotoxic T lymphocyte therapy for patients with relapsed B cell malignancies after allogeneic haematopoietic stem cell transplantation SO BONE MARROW TRANSPLANTATION LA English DT Meeting Abstract CT 38th Annual Meeting of the European-Group-for-Blood-and-Marrow-Transplantation (EBMT) CY APR 01-04, 2012 CL Geneva, SWITZERLAND SP European Grp Blood & Marrow Transplantat (EBMT) C1 [Bollard, C.; Cruz, C.; Savoldo, B.; Krance, R.; Kamble, R.; Heslop, H.; Leen, A.; Rooney, C.; Brenner, M.; Dotti, G.] Baylor Coll Med, Houston, TX 77030 USA. [Barrett, A.] NHLBI, NIH, Bethesda, MD 20892 USA. [Hosing, C.; Shpall, E.] Univ Texas Houston, MD Anderson Canc Ctr, Houston, TX 77030 USA. NR 0 TC 2 Z9 2 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0268-3369 J9 BONE MARROW TRANSPL JI Bone Marrow Transplant. PD APR PY 2012 VL 47 SU 1 BP S56 EP S56 PG 1 WC Biophysics; Oncology; Hematology; Immunology; Transplantation SC Biophysics; Oncology; Hematology; Immunology; Transplantation GA 925GN UT WOS:000302749200120 ER PT J AU de Latour, RP Calado, R Busson, M Abrams, J Robin, M Larghero, J Xhaard, A Dhedin, N Clave, E Charron, D Toubert, A Loiseau, P Socie, G Young, N AF de Latour, R. Peffault Calado, R. Busson, M. Abrams, J. Robin, M. Larghero, J. Xhaard, A. Dhedin, N. Clave, E. Charron, D. Toubert, A. Loiseau, P. Socie, G. Young, N. TI Age-adjusted recipient pre transplant telomere length and treatment-related mortality after haematopoietic stem cell transplantation SO BONE MARROW TRANSPLANTATION LA English DT Meeting Abstract CT 38th Annual Meeting of the European-Group-for-Blood-and-Marrow-Transplantation (EBMT) CY APR 01-04, 2012 CL Geneva, SWITZERLAND SP European Grp Blood & Marrow Transplantat (EBMT) C1 [de Latour, R. Peffault; Busson, M.; Robin, M.; Larghero, J.; Xhaard, A.; Dhedin, N.; Clave, E.; Charron, D.; Toubert, A.; Loiseau, P.; Socie, G.] Hop St Louis, Paris, France. [Calado, R.; Abrams, J.; Young, N.] NIH, Bethesda, MD 20892 USA. RI Calado, Rodrigo/G-2619-2011 NR 0 TC 0 Z9 0 U1 0 U2 1 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0268-3369 J9 BONE MARROW TRANSPL JI Bone Marrow Transplant. PD APR PY 2012 VL 47 SU 1 BP S28 EP S28 PG 1 WC Biophysics; Oncology; Hematology; Immunology; Transplantation SC Biophysics; Oncology; Hematology; Immunology; Transplantation GA 925GN UT WOS:000302749200053 ER PT J AU Grkovic, L Pulanic, D Steinberg, SM Williams, KM Baird, K Mitchell, SA Cowen, EW Datiles, MB Aria, D Bassim, C Joe, G Comis, L Baruffaldi, J Zhang, D Sportes, C Fowler, DH Hakim, F Gress, RE Pavletic, SZ AF Grkovic, L. Pulanic, D. Steinberg, S. M. Williams, K. M. Baird, K. Mitchell, S. A. Cowen, E. W. Datiles, M. B., III Aria, D. Bassim, C. Joe, G. Comis, L. Baruffaldi, J. Zhang, D. Sportes, C. Fowler, D. H. Hakim, F. Gress, R. E. Pavletic, S. Z. TI NIH lung score components are associated with clinical outcomes, Bronchiolitis obliterans syndrome and survival in chronic GvHD SO BONE MARROW TRANSPLANTATION LA English DT Meeting Abstract CT 38th Annual Meeting of the European-Group-for-Blood-and-Marrow-Transplantation (EBMT) CY APR 01-04, 2012 CL Geneva, SWITZERLAND SP European Grp Blood & Marrow Transplantat (EBMT) C1 [Grkovic, L.; Pulanic, D.] Clin Hosp Ctr Zagreb, Zagreb, Croatia. [Steinberg, S. M.; Williams, K. M.; Baird, K.; Mitchell, S. A.; Cowen, E. W.; Datiles, M. B., III; Aria, D.; Bassim, C.; Joe, G.; Comis, L.; Baruffaldi, J.; Zhang, D.; Sportes, C.; Fowler, D. H.; Hakim, F.; Gress, R. E.; Pavletic, S. Z.] NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0268-3369 J9 BONE MARROW TRANSPL JI Bone Marrow Transplant. PD APR PY 2012 VL 47 SU 1 BP S61 EP S61 PG 1 WC Biophysics; Oncology; Hematology; Immunology; Transplantation SC Biophysics; Oncology; Hematology; Immunology; Transplantation GA 925GN UT WOS:000302749200132 ER PT J AU Hanley, P Martinez, C Melenhorst, J Leung, K Savoldo, B Leen, A Dotti, G Gee, A Rooney, C Heslop, H Krance, R Barrett, A Shpall, E Bollard, C AF Hanley, P. Martinez, C. Melenhorst, J. Leung, K. Savoldo, B. Leen, A. Dotti, G. Gee, A. Rooney, C. Heslop, H. Krance, R. Barrett, A. Shpall, E. Bollard, C. TI Administration of cord blood (CB)-derived virus-specific cytotoxic T lymphocytes to prevent CMV, adenovirus, and EBV infection after CB transplant SO BONE MARROW TRANSPLANTATION LA English DT Meeting Abstract CT 38th Annual Meeting of the European-Group-for-Blood-and-Marrow-Transplantation (EBMT) CY APR 01-04, 2012 CL Geneva, SWITZERLAND SP European Grp Blood & Marrow Transplantat (EBMT) C1 [Hanley, P.; Martinez, C.; Melenhorst, J.; Leung, K.; Savoldo, B.; Leen, A.; Dotti, G.; Gee, A.; Rooney, C.; Heslop, H.; Krance, R.; Bollard, C.] Baylor Coll Med, Houston, TX 77030 USA. [Barrett, A.] NHLBI, NIH, Bethesda, MD 20892 USA. [Shpall, E.] Univ Texas Houston, MD Anderson Canc Ctr, Houston, TX 77030 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0268-3369 J9 BONE MARROW TRANSPL JI Bone Marrow Transplant. PD APR PY 2012 VL 47 SU 1 BP S56 EP S56 PG 1 WC Biophysics; Oncology; Hematology; Immunology; Transplantation SC Biophysics; Oncology; Hematology; Immunology; Transplantation GA 925GN UT WOS:000302749200119 ER PT J AU Kirsch, M Mitchell, SA Halter, J Stussi, G Dobbels, F Basch, E De Geest, S AF Kirsch, M. Mitchell, S. A. Halter, J. Stussi, G. Dobbels, F. Basch, E. De Geest, S. TI Development of a Patient Reported Outcome instrument for assessing symptoms of late effects in survivors after allogeneic stem cell transplantation: PROVIVO - a mixed methods study SO BONE MARROW TRANSPLANTATION LA English DT Meeting Abstract CT 38th Annual Meeting of the European-Group-for-Blood-and-Marrow-Transplantation (EBMT) CY APR 01-04, 2012 CL Geneva, SWITZERLAND SP European Grp Blood & Marrow Transplantat (EBMT) C1 [Kirsch, M.; De Geest, S.] Univ Basel, Inst Nursing Sci, Basel, Switzerland. [Mitchell, S. A.] NCI, Bethesda, MD 20892 USA. [Halter, J.] Univ Basel Hosp, CH-4031 Basel, Switzerland. [Stussi, G.] Oncol Inst So Switzerland, Bellinzona, Switzerland. [Dobbels, F.] Katholieke Univ Leuven, Louvain, Belgium. [Basch, E.] Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0268-3369 J9 BONE MARROW TRANSPL JI Bone Marrow Transplant. PD APR PY 2012 VL 47 SU 1 BP S462 EP S462 PG 1 WC Biophysics; Oncology; Hematology; Immunology; Transplantation SC Biophysics; Oncology; Hematology; Immunology; Transplantation GA 925GN UT WOS:000302749202012 ER PT J AU Williams, K Pavletic, S Lee, S Hakim, F Mitchell, S Manning-Geist, BL Gea-Banacloche, J Comis, L Cowen, E Baird, K Shelhamer, J Blacklock-Schuver, B Avila, D Zulchinski, D Gress, R AF Williams, K. Pavletic, S. Lee, S. Hakim, F. Mitchell, S. Manning-Geist, B. L. Gea-Banacloche, J. Comis, L. Cowen, E. Baird, K. Shelhamer, J. Blacklock-Schuver, B. Avila, D. Zulchinski, D. Gress, R. TI Preliminary results of a phase II trial of montelukast for the treatment of Bronchiolitis obliterans syndrome after HSCT and implications for immunobiology of disease SO BONE MARROW TRANSPLANTATION LA English DT Meeting Abstract CT 38th Annual Meeting of the European-Group-for-Blood-and-Marrow-Transplantation (EBMT) CY APR 01-04, 2012 CL Geneva, SWITZERLAND SP European Grp Blood & Marrow Transplantat (EBMT) C1 [Williams, K.; Pavletic, S.; Hakim, F.; Mitchell, S.; Manning-Geist, B. L.; Gea-Banacloche, J.; Comis, L.; Cowen, E.; Baird, K.; Blacklock-Schuver, B.; Avila, D.; Zulchinski, D.; Gress, R.] NCI, Bethesda, MD 20892 USA. [Lee, S.] Fred Hutchinson Canc Res Ctr, Seattle, WA 98104 USA. [Shelhamer, J.] NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 2 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0268-3369 J9 BONE MARROW TRANSPL JI Bone Marrow Transplant. PD APR PY 2012 VL 47 SU 1 BP S61 EP S61 PG 1 WC Biophysics; Oncology; Hematology; Immunology; Transplantation SC Biophysics; Oncology; Hematology; Immunology; Transplantation GA 925GN UT WOS:000302749200131 ER PT J AU Cramer, SC AF Cramer, Steven C. TI Reply: Harnessing neuroplasticity for clinical applications SO BRAIN LA English DT Letter C1 [Cramer, Steven C.] NIMH, Neurodev Disorders Res Branch, Bethesda, MD 20892 USA. RP Cramer, SC (reprint author), Univ Calif Irvine, UC Irvine Med Ctr, 101 City Dr S,Bldg 53,Room 203, Orange, CA 92868 USA. EM scramer@uci.edu NR 0 TC 0 Z9 0 U1 0 U2 3 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0006-8950 J9 BRAIN JI Brain PD APR PY 2012 VL 135 AR e216 DI 10.1093/brain/aws018 PN 4 PG 1 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 927ZH UT WOS:000302948700006 ER PT J AU Fukuto, JM Carrington, SJ Tantillo, DJ Harrison, JG Ignarro, LJ Freeman, BA Chen, A Wink, DA AF Fukuto, Jon M. Carrington, Samantha J. Tantillo, Dean J. Harrison, Jason G. Ignarro, Louis J. Freeman, Bruce A. Chen, Andrew Wink, David A. TI Small Molecule Signaling Agents: The Integrated Chemistry and Biochemistry of Nitrogen Oxides, Oxides of Carbon, Dioxygen, Hydrogen Sulfide, and Their Derived Species SO CHEMICAL RESEARCH IN TOXICOLOGY LA English DT Review ID CYSTATHIONINE-BETA-SYNTHASE; BOND-DISSOCIATION ENERGIES; HYPOXIA-INDUCIBLE FACTOR-1-ALPHA; METAL-NITROSYL COMPLEXES; HUMAN SERUM-ALBUMIN; NITRIC-OXIDE; SUPEROXIDE-DISMUTASE; AQUEOUS-SOLUTION; REACTIVE OXYGEN; S-NITROSOTHIOLS AB Several small molecule species formally known primarily as toxic gases have, over the past 20 years, been shown to be endogenously generated signaling molecules. The biological signaling associated with the small molecules NO, CO, H2S (and the nonendogenously generated O-2), and their derived species have become a topic of extreme interest. It has become increasingly clear that these small molecule signaling agents form an integrated signaling web that affects/regulates numerous physiological processes. The chemical interactions between these species and each other or biological targets is an important factor in their roles as signaling agents. Thus, a fundamental understanding of the chemistry of these molecules is essential to understanding their biological/physiological utility. This review focuses on this chemistry and attempts to establish the chemical basis for their signaling functions. C1 [Fukuto, Jon M.; Carrington, Samantha J.; Chen, Andrew] Sonoma State Univ, Dept Chem, Rohnert Pk, CA 94928 USA. [Tantillo, Dean J.; Harrison, Jason G.] Univ Calif Davis, Dept Chem, Davis, CA 95616 USA. [Ignarro, Louis J.] UCLA Sch Med, Ctr Hlth Sci, Dept Mol & Med Pharmacol, Los Angeles, CA 90095 USA. [Freeman, Bruce A.] Univ Pittsburgh, Dept Pharmacol & Chem Biol, Pittsburgh, PA 15261 USA. [Wink, David A.] NCI, Tumor Biol Sect, Radiat Biol Branch, Bethesda, MD 20892 USA. RP Fukuto, JM (reprint author), Sonoma State Univ, Dept Chem, Rohnert Pk, CA 94928 USA. EM jon.fukuto@sonoma.edu RI Freeman, Bruce/H-9342-2012; Carrington, Samantha/F-5848-2014 FU NHLBI NIH HHS [R01 HL058115, R01 HL064937, R37 HL058115] NR 183 TC 89 Z9 90 U1 5 U2 74 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0893-228X J9 CHEM RES TOXICOL JI Chem. Res. Toxicol. PD APR PY 2012 VL 25 IS 4 BP 769 EP 793 DI 10.1021/tx2005234 PG 25 WC Chemistry, Medicinal; Chemistry, Multidisciplinary; Toxicology SC Pharmacology & Pharmacy; Chemistry; Toxicology GA 926JA UT WOS:000302826000001 PM 22263838 ER PT J AU Insel, TR AF Insel, Thomas R. TI Invited Response to: Preparedness of the CTSA's Structural and Scientific Assets to Support the Mission of the National Center for Advancing Translational Sciences (NCATS) SO CTS-CLINICAL AND TRANSLATIONAL SCIENCE LA English DT Article C1 [Insel, Thomas R.] NCATS, Bethesda, MD USA. [Insel, Thomas R.] NIMH, Bethesda, MD 20892 USA. RP Insel, TR (reprint author), NCATS, Bethesda, MD USA. EM tinsel@mail.nih.gov NR 2 TC 1 Z9 1 U1 0 U2 1 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1752-8054 J9 CTS-CLIN TRANSL SCI JI CTS-Clin. Transl. Sci. PD APR PY 2012 VL 5 IS 2 BP 130 EP 131 DI 10.1111/j.1752-8062.2012.00408.x PG 2 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 926VT UT WOS:000302860700006 PM 22507117 ER PT J AU Meyers, FJ Begg, MD Fleming, M Merchant, C AF Meyers, Frederick J. Begg, Melissa D. Fleming, Michael Merchant, Carol TI Strengthening the Career Development of Clinical Translational Scientist Trainees: A Consensus Statement of the Clinical Translational Science Award (CTSA) Research Education and Career Development Committees SO CTS-CLINICAL AND TRANSLATIONAL SCIENCE LA English DT Article DE Clinical and Translational Science Award (CTSA); Education and Career Development (EdCD) key function committee; interdisciplinary; competencies; mentoring ID RESEARCH MENTORS; INTERDISCIPLINARY RESEARCH; SCHOLARS AB The challenges for scholars committed to successful careers in clinical and translational science are increasingly well recognized. The Education and Career Development (EdCD) of the national Clinical and Translational Science Award consortium gathered thought leaders to propose sustainable solutions and an agenda for future studies that would strengthen the infrastructure across the spectrum of pre- and postdoctoral, MD and PhD, scholars. Six consensus statements were prepared that include: (1) the requirement for career development of a qualitatively different investigator; (2) the implications of interdisciplinary science for career advancement including institutional promotion and tenure actions that were developed for discipline-specific accomplishments; (3) the need for long-term commitment of institutions to scholars; (4) discipline-specific curricula are still required but curricula designed to promote team work and interdisciplinary training will promote innovation; (5) PhD trainees have many pathways to career satisfaction and success; and (6) a centralized infrastructure to enhance and reward mentoring is required. Several themes cut across all of the recommendations including team science, innovation, and sustained institutional commitment. Implied themes include an effective and diverse job force and the requirement for a well-crafted public policy that supports continued investments in science education. Clin Trans Sci 2012; Volume #: 16 C1 [Meyers, Frederick J.] Univ Calif Davis, Sch Med, Sacramento, CA 95817 USA. [Begg, Melissa D.] Mailman Sch Publ Hlth, New York, NY USA. [Begg, Melissa D.] Irving Inst Clin & Translat Res, New York, NY USA. [Fleming, Michael] Feinberg Sch Med, Chicago, IL USA. [Merchant, Carol] NIH, Natl Ctr Res Resources, Bethesda, MD 20892 USA. RP Meyers, FJ (reprint author), Univ Calif Davis, Sch Med, Sacramento, CA 95817 USA. EM fred.meyers@ucdmc.ucdavis.edu FU Clinical Translational Science award; [UC Davis UL1RR024146]; [Columbia UL1RR024156]; [Northwestern UL1RR025741] FX This work was supported by Clinical Translational Science award and Grants: UC Davis UL1RR024146, Columbia UL1RR024156, and Northwestern UL1RR025741. NR 34 TC 21 Z9 21 U1 1 U2 15 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1752-8054 J9 CTS-CLIN TRANSL SCI JI CTS-Clin. Transl. Sci. PD APR PY 2012 VL 5 IS 2 BP 132 EP 137 DI 10.1111/j.1752-8062.2011.00392.x PG 6 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 926VT UT WOS:000302860700007 PM 22507118 ER PT J AU Rubio, DM Sufian, M Trochim, WM AF Rubio, Doris McGartland Sufian, Meryl Trochim, William M. TI Strategies for a National Evaluation of the Clinical and Translational Science Awards SO CTS-CLINICAL AND TRANSLATIONAL SCIENCE LA English DT Article ID MODEL C1 [Rubio, Doris McGartland] Univ Pittsburgh, Sch Med, Dept Med, Ctr Res Hlth Care Data Ctr,Div Gen Internal Med, Pittsburgh, PA 15260 USA. [Rubio, Doris McGartland] Univ Pittsburgh, Clin & Translat Sci Inst, Pittsburgh, PA USA. [Sufian, Meryl] NIH, Off Sci & Policy, Natl Ctr Res Resources, Bethesda, MD 20892 USA. [Trochim, William M.] Cornell Univ, Dept Policy Anal & Management, Ithaca, NY USA. [Trochim, William M.] Weill Cornell Med Coll, Clin & Translat Sci Ctr, New York, NY USA. RP Rubio, DM (reprint author), Univ Pittsburgh, Sch Med, Dept Med, Ctr Res Hlth Care Data Ctr,Div Gen Internal Med, Pittsburgh, PA 15260 USA. EM rubiodm@upmc.edu FU National Center for Research Resources (NCRR); National Institutes of Health (NIH); NCRR/NIH CTSA [UL1 RR024153, UL1 RR024996] FX The project reported here was supported in part by the National Center for Research Resources (NCRR) and the National Institutes of Health (NIH) through the Clinical and Translational Science Award (CTSA) Program. The NCRR/NIH CTSA funding was awarded to the University of Pittsburgh (UL1 RR024153) and Cornell University (UL1 RR024996). NR 7 TC 5 Z9 6 U1 1 U2 4 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1752-8054 J9 CTS-CLIN TRANSL SCI JI CTS-Clin. Transl. Sci. PD APR PY 2012 VL 5 IS 2 BP 138 EP 139 DI 10.1111/j.1752-8062.2011.00381.x PG 2 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 926VT UT WOS:000302860700008 PM 22507119 ER PT J AU Zarin, DA AF Zarin, Deborah A. TI Factual Errors about ClinicalTrials.gov and Other Federal Mandates in Special Report by Shuster SO CTS-CLINICAL AND TRANSLATIONAL SCIENCE LA English DT Letter C1 Natl Lib Med, ClinicalTrials Gov, Bethesda, MD 20894 USA. RP Zarin, DA (reprint author), Natl Lib Med, ClinicalTrials Gov, Bethesda, MD 20894 USA. EM dzarin@mail.nih.gov NR 3 TC 1 Z9 1 U1 0 U2 1 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1752-8054 J9 CTS-CLIN TRANSL SCI JI CTS-Clin. Transl. Sci. PD APR PY 2012 VL 5 IS 2 BP 217 EP 217 DI 10.1111/j.1752-8062.2012.00411.x PG 1 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 926VT UT WOS:000302860700011 PM 22507123 ER PT J AU Shechner, T Britton, JC Perez-Edgar, K Bar-Haim, Y Ernst, M Fox, NA Leibenluft, E Pine, DS AF Shechner, Tomer Britton, Jennifer C. Perez-Edgar, Koraly Bar-Haim, Yair Ernst, Monique Fox, Nathan A. Leibenluft, Ellen Pine, Daniel S. TI Attention biases, anxiety, and development: toward or away from threats or rewards? SO DEPRESSION AND ANXIETY LA English DT Review DE attention bias; anxiety; brain-behavior; attention training ID POSTTRAUMATIC-STRESS-DISORDER; PREFRONTAL CORTEX ACTIVATION; ANTICIPATED PEER EVALUATION; MAJOR DEPRESSIVE DISORDER; GENERALIZED-ANXIETY; BEHAVIORAL-INHIBITION; SELECTIVE ATTENTION; SOCIAL ANXIETY; ANGRY FACES; EMOTIONAL INFORMATION AB Research on attention provides a promising framework for studying anxiety pathophysiology and treatment. The study of attention biases appears particularly pertinent to developmental research, as attention affects learning and has down-stream effects on behavior. This review summarizes recent findings about attention orienting in anxiety, drawing on findings in recent developmental psychopathology and affective neuroscience research. These findings generate specific insights about both development and therapeutics. The review goes beyond a traditional focus on biased processing of threats and considers biased processing of rewards. Building on this work, we then turn to the treatment of pediatric anxiety, where manipulation of attention to threat and/or reward may serve a therapeutic role as a component of Attention Bias Modification Therapy. Depression and Anxiety 0:113, 2011. (C) 2011 Wiley Periodicals, Inc. C1 [Shechner, Tomer] NIMH, Sect Dev Affect Neurosci, Bethesda, MD 20892 USA. [Perez-Edgar, Koraly] George Mason Univ, Dept Psychol, Arlington, VA USA. [Bar-Haim, Yair] Tel Aviv Univ, Dept Psychol, IL-69978 Tel Aviv, Israel. [Fox, Nathan A.] Univ Maryland, Dept Human Dev, College Pk, MD 20742 USA. RP Shechner, T (reprint author), NIMH, Sect Dev Affect Neurosci, 9000 Rockville Pike,Bldg 15K,Rm 208, Bethesda, MD 20892 USA. EM shechnert@mail.nih.gov RI Britton, Jennifer/J-4501-2013; OI Perez-Edgar, Koraly/0000-0003-4051-9563 FU National Institutes of Mental Heatlh FX The authors disclose the following financial relationships within the past 3 years: The paper was supported in part by the Intramural Research Program of the National Institutes of Mental Heatlh. NR 77 TC 67 Z9 68 U1 10 U2 87 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1091-4269 J9 DEPRESS ANXIETY JI Depress. Anxiety PD APR PY 2012 VL 29 IS 4 BP 282 EP 294 DI 10.1002/da.20914 PG 13 WC Psychology, Clinical; Psychiatry; Psychology SC Psychology; Psychiatry GA 927KG UT WOS:000302905600005 PM 22170764 ER PT J AU Cawley, NX Wetsel, WC Murthy, SRK Park, JJ Pacak, K Loh, YP AF Cawley, Niamh X. Wetsel, William C. Murthy, Saravana R. K. Park, Joshua J. Pacak, Karel Loh, Y. Peng TI New Roles of Carboxypeptidase E in Endocrine and Neural Function and Cancer SO ENDOCRINE REVIEWS LA English DT Review ID NEUROPEPTIDE-PROCESSING ENZYME; REGULATED SECRETORY PATHWAY; CENTRAL-NERVOUS-SYSTEM; DIFFERENTIAL GENE-EXPRESSION; ACTIVITY-DEPENDENT SECRETION; EXPERIMENTAL AUTOIMMUNE ENCEPHALOMYELITIS; H-3 GUANIDINOETHYLMERCAPTOSUCCINIC ACID; VESICULAR ACETYLCHOLINE TRANSPORTER; CPE(FAT/FAT) MOUSE HYPOTHALAMUS; SINGLE NUCLEOTIDE POLYMORPHISM AB Carboxypeptidase E (CPE) or carboxypeptidase H was first discovered in 1982 as an enkephalin-convertase that cleaved a C-terminal basic residue from enkephalin precursors to generate enkephalin. Since then, CPE has been shown to be a multifunctional protein that subserves many essential nonenzymatic roles in the endocrine and nervous systems. Here, we review the phylogeny, structure, and function of CPE in hormone and neuropeptide sorting and vesicle transport for secretion, alternative splicing of the CPE transcript, and single nucleotide polymorphisms in humans. With this and the analysis of mutant and knockout mice, the data collectively support important roles for CPE in the modulation of metabolic and glucose homeostasis, bone remodeling, obesity, fertility, neuroprotection, stress, sexual behavior, mood and emotional responses, learning, and memory. Recently, a splice variant form of CPE has been found to be an inducer of tumor growth and metastasis and a prognostic biomarker for metastasis in endocrine and nonendocrine tumors. (Endocrine Reviews 33: 216-253, 2012) C1 [Cawley, Niamh X.; Murthy, Saravana R. K.; Loh, Y. Peng] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Cellular Neurobiol Sect, Program Dev Neurosci, NIH, Bethesda, MD 20892 USA. [Wetsel, William C.] Duke Univ, Med Ctr, Dept Psychiat & Behav Sci, Durham, NC 27710 USA. [Wetsel, William C.] Duke Univ, Med Ctr, Dept Cell Biol, Durham, NC 27710 USA. [Wetsel, William C.] Duke Univ, Med Ctr, Dept Med Endocrinol, Durham, NC 27710 USA. [Wetsel, William C.] Duke Univ, Med Ctr, Dept Neurobiol, Durham, NC 27710 USA. [Park, Joshua J.] Univ Toledo, Coll Med, Dept Neurosci, Toledo, OH 43614 USA. [Pacak, Karel] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Program Reprod & Adult Endocrinol, NIH, Bethesda, MD 20892 USA. RP Loh, YP (reprint author), Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Cellular Neurobiol Sect, Program Dev Neurosci, NIH, 49 Convent Dr,Bldg 49,Room 5A-22, Bethesda, MD 20892 USA. EM lohp@mail.nih.gov FU Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD); NICHD FX Research in the authors' laboratories was supported in part by the Intramural Research Program of the Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) (to N.X.C., S. R. K. M., and K. P.), and NICHD K22 and American Recovery and Reinvestment Act grants (to J.J.P.). NR 365 TC 41 Z9 43 U1 1 U2 8 PU ENDOCRINE SOC PI WASHINGTON PA 2055 L ST NW, SUITE 600, WASHINGTON, DC 20036 USA SN 0163-769X EI 1945-7189 J9 ENDOCR REV JI Endocr. Rev. PD APR PY 2012 VL 33 IS 2 BP 216 EP 253 DI 10.1210/er.2011-1039 PG 38 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 925PZ UT WOS:000302774700003 PM 22402194 ER PT J AU Mao, WM Rubin, JS Anoruo, N Wordinger, RJ Clark, AF AF Mao, Weiming Rubin, Jeffrey S. Anoruo, Nancy Wordinger, Robert J. Clark, Abbot F. TI SFRP1 promoter methylation and expression in human trabecular meshwork cells SO EXPERIMENTAL EYE RESEARCH LA English DT Article DE glaucoma; intraocular pressure; trabecular meshwork; SFRP1; DNA methylation; 5-aza-2 '-deoxycytidine ID ELEVATES INTRAOCULAR-PRESSURE; FRIZZLED-RELATED PROTEINS; AQUEOUS-HUMOR; EPIGENETIC INACTIVATION; GLAUCOMATOUS EYES; DNA METHYLATION; GASTRIC-CANCER; CURVE ANALYSIS; WNT; GREMLIN AB Glaucoma is a leading cause of blindness worldwide. In primary open angle glaucoma (POAG) patients, impaired trabecular meshwork (TM) function results in elevated intraocular pressure (IOP), which is the primary risk factor of developing optic neuropathy. Our previous studies showed that Wnt signaling pathway components are expressed in the human TM (HTM), and the Wnt inhibitor, secreted frizzled-related protein 1 (SFRP1) is elevated in the glaucomatous TM (GTM). Elevated SFRP1 increased IOP in mice eyes and in perfusion cultured anterior segments of the human eye. However, the cause of elevated SFRP1 in the GTM remains unknown. Promoter methylation plays a key role in regulating SFRP1 expression in certain cancer cells. In light of this, we studied whether promoter methylation is also involved in SFRP1 differential expression in the TM. Two normal TM (NTM) and two GTM cell strains were cultured for an additional 7 days after they were confluent. RNA and genomic DNA (gDNA) were isolated simultaneously to compare SFRP1 expression levels by quantitative PCR (qPCR) and to determine SFRP1 promoter methylation status by bisulfite conversion and methylation-sensitive high resolution melting analysis (MS-HRM). To study whether DNA methylation inhibitors affect SFRP1 expression in TM cells, the four TM cell strains were treated with or without 2 mu M 5-aza-2'-deoxycytidine (AZA-dC) for 4 days. RNA was isolated to compare SFRP1 expression by qPCR. In addition, a human cancer cell line, NCI-H460, was used as a positive control. We found that the two GTM cell strains had significantly higher expression levels of SFRP1 than the two NTM cell strains. However, the SFRP1 promoter of all four TM cell strains was unmethylated. In addition, AZA-dC treatment did not affect SFRP1 expression in any of the TM cell strains (n = 3, p > 0.05). In contrast, the hypermethylated SFRP1 promoter of NCI-H460 cells was partially demethylated by the same treatment. AZA-dC treatment also elevated SFRP1 expression by approximately two fold in NCI-H460 cells (n = 3, p < 0.01). Our data suggest that the differential expression of SFRP1 in HTM cells is not due to differential promoter methylation. (C) 2012 Elsevier Ltd. All rights reserved. C1 [Mao, Weiming; Wordinger, Robert J.; Clark, Abbot F.] Univ N Texas, Hlth Sci Ctr, Dept Cell Biol & Anat, N Texas Eye Res Inst, Ft Worth, TX 76107 USA. [Rubin, Jeffrey S.; Anoruo, Nancy] NCI, Cellular & Mol Biol Lab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. RP Mao, WM (reprint author), Univ N Texas, Hlth Sci Ctr, Dept Cell Biol & Anat, N Texas Eye Res Inst, CBH440, Ft Worth, TX 76107 USA. EM weiming.mao@unthsc.edu OI Wordinger, Robert/0000-0002-2861-8967 NR 39 TC 7 Z9 9 U1 1 U2 6 PU ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD PI LONDON PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND SN 0014-4835 J9 EXP EYE RES JI Exp. Eye Res. PD APR PY 2012 VL 97 IS 1 BP 130 EP 136 DI 10.1016/j.exer.2012.01.003 PG 7 WC Ophthalmology SC Ophthalmology GA 929QU UT WOS:000303081400015 PM 22248913 ER PT J AU Young, NS AF Young, Neal S. TI Bone marrow failure and the new telomere diseases: practice and research SO HEMATOLOGY LA English DT Article DE Cirrhosis; Pulmonary fibrosis; Aplastic anemia; Genetics ID DYSKERATOSIS-CONGENITA; LENGTH AB The telomeropathies are a newly described group of human diseases based on the genetics and molecular biology of the telomeres, the ends of chromosomes. Telomeres are repeated hexanucleotides and their associated proteins; the protect chromosomes from recognition as damaged DNA, and their inevitable gradual loss with DNA replication is harmless as they are noncoding. However, when telomeres become critically short in a cell, senescence, apoptosis, or, rarely malignant transformation results. In individuals with mutations in genes involved in telomere repair, especially the enzymatic telomerase complex, telomere attrition is accelerated. Severe deficiencies result in dyskeratosis congenita, a congenital aplastic anemia with associated mucocutaneous abnormalities. Mutations in TERT, the catalytic component, and TERC, the RNA template, can behave as risk factors for the development of bone marrow failure, pulmonary fibrosis, and hepatic cirrhosis. Both penetrance and organ specificity are variable and not well understood. Chromosome instability is a result of critical shortening of telomeres and cancer. For example, short telomeres are the major prognostic risk factor for clonal evolution to myelodysplasia and acute leukemia. Practically, hematologists need to recognize the multisystem presentation of telomere disease, implications for outcomes, and options for therapy. C1 NHLBI, Hematol Branch, NIH, Bethesda, MD 20892 USA. RP Young, NS (reprint author), NHLBI, Hematol Branch, NIH, Bethesda, MD 20892 USA. EM youngns@nhlbi.nih.gov NR 11 TC 14 Z9 16 U1 0 U2 9 PU MANEY PUBLISHING PI LEEDS PA STE 1C, JOSEPHS WELL, HANOVER WALK, LEEDS LS3 1AB, W YORKS, ENGLAND SN 1024-5332 J9 HEMATOLOGY JI Hematology PD APR PY 2012 VL 17 SU 1 BP S18 EP S21 DI 10.1179/102453312X13336169155132 PG 4 WC Hematology SC Hematology GA 927OA UT WOS:000302916200006 PM 22507770 ER PT J AU McCarthy, AM Wehby, GL Barron, S Aylward, GP Castilla, EE Javois, LC Goco, N Murray, JC AF McCarthy, Ann Marie Wehby, George L. Barron, Sheila Aylward, Glen P. Castilla, Eduardo E. Javois, Lorette C. Goco, Norman Murray, Jeffrey C. TI Application of neurodevelopmental screening to a sample of South American infants: The Bayley Infant Neurodevelopmental Screener (BINS) SO INFANT BEHAVIOR & DEVELOPMENT LA English DT Article DE Developmental screening; Infants; South America; Bayley Infant Neurodevelopmental; Screener ID COGNITIVE-DEVELOPMENT; YOUNG-CHILDREN; HEALTH; RISK; BORN AB Objective: To evaluate the utility of the Bayley Infant Neurodevelopmental Screener (BINS), standardized in the US, for South American infants, 3-24 months of age. Methods: Thirty-five physicians administered the BINS to 2471 South American infants recruited during routine well-child visits, 578 (23%) from Brazil and 1893 (77%) from six other South American countries. The BINS was translated into Spanish and Portuguese and participating physicians were trained to administer the BINS. Physician inter-rater agreement with training tapes was 84.4%; test-retest reliability for age item sets ranged from 0.80 to 0.93 (Pearson's r). Infants were classified into being at low, moderate, or high risk for developmental delay or neurological impairment based on their total BINS score. The sample was stratified by infant's age, sex and language (Spanish and Portuguese). The BINS scores were compared to the scores of the US infant sample used to standardize the BINS. Results: Female infants performed higher than male at 16-20 months and 21-24 months: male infant scores were more variable at 5-6 months. Scores on only two items were significantly different between Spanish and Portuguese speaking participants. South American scores were typically significantly higher than the US sample, and a lower proportion of infants were classified as being at high risk in the South American sample than in the US standardization sample. Conclusion: Overall, the results of this study indicate that the BINS is feasible and appropriate for neurodevelopmental screening in South America. Further studies are needed to confirm the BINS utility in South America, including its use with a clinical sample. (C) 2012 Elsevier Inc. All rights reserved. C1 [McCarthy, Ann Marie] Univ Iowa, Coll Nursing, Iowa City, IA 52242 USA. [Wehby, George L.] Univ Iowa, Coll Publ Hlth, Iowa City, IA 52242 USA. [Barron, Sheila] Univ Iowa, Stat Outreach Ctr, Coll Educ, Iowa City, IA 52242 USA. [Aylward, Glen P.] So Illinois Univ, Sch Med, Div Dev & Behav Pediat Psychol, Springfield, IL USA. [Castilla, Eduardo E.] CEMIC, Inst Nacl Genet Med Populac INAGEMP, Buenos Aires, DF, Argentina. [Castilla, Eduardo E.] Fundacao Oswald Cruz, Inst Oswaldo Cruz, Lab Epidemiol Malformacees Congenitas, Rio De Janeiro, Brazil. [Javois, Lorette C.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Dev Biol Genet & Teratol Branch, Ctr Dev Biol & Perinatal Med, NIH, Bethesda, MD USA. [Goco, Norman] RTI Int, Res Triangle Pk, NC USA. [Murray, Jeffrey C.] Univ Iowa, Dept Pediat, Iowa City, IA 52242 USA. RP McCarthy, AM (reprint author), Univ Iowa, Coll Nursing, 50 Newton Rd,CNB 344, Iowa City, IA 52242 USA. EM ann-mccarthy@uiowa.edu RI Inagemp, Inct/J-9451-2013 FU NICHD NIH HHS [1U01 HD-40561-05S2, U01 HD040561, U01 HD040561-05S2, U01 HD040636] NR 28 TC 7 Z9 7 U1 0 U2 3 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0163-6383 EI 1879-0453 J9 INFANT BEHAV DEV JI Infant Behav. Dev. PD APR PY 2012 VL 35 IS 2 BP 280 EP 294 DI 10.1016/j.infbeh.2011.12.003 PG 15 WC Psychology, Developmental SC Psychology GA 929AN UT WOS:000303033700011 PM 22244313 ER PT J AU Maalouf, FT Porta, G Vitiello, B Emslie, G Mayes, T Clarke, G Wagner, KD Asarnow, JR Spirito, A Keller, M Birmaher, B Ryan, N Shamseddeen, W Iyengar, S Brent, D AF Maalouf, Fadi T. Porta, Giovanna Vitiello, Benedetto Emslie, Graham Mayes, Taryn Clarke, Gregory Wagner, Karen D. Asarnow, Joan Rosenbaum Spirito, Anthony Keller, Martin Birmaher, Boris Ryan, Neal Shamseddeen, Wael Iyengar, Satish Brent, David TI Do sub-syndromal manic symptoms influence outcome in treatment resistant depression in adolescents? A latent class analysis from the TORDIA study SO JOURNAL OF AFFECTIVE DISORDERS LA English DT Article DE TORDIA; Trajectories; Latent class analysis; Depression; Adolescent ID COGNITIVE-BEHAVIORAL THERAPY; RANDOMIZED CONTROLLED-TRIAL; BIPOLAR SPECTRUM DISORDERS; TREATMENT RESPONSE; OLDER ADOLESCENTS; COMMUNITY SAMPLE; RATING-SCALE; PREDICTORS; CHILDREN; REMISSION AB Background: To identify distinct depressive symptom trajectories in the TORDIA study and determine their correlates. Methods: Latent Class Growth Analysis (LCGA) using the Children's Depression Rating Scale Revised (CDRS-R) through 72 weeks from intake. Results: 3 classes were identified: (1) little change in symptomatic status ("NO"), comprising 24.9% of participants, with a 72-week remission rate of 25.3%; (2) slow, steady improvement ("SLOW"), comprising 47.9% of participants, with a remission rate of 60.0%, and (3) rapid symptom response ("GO"), comprising 27.2% of participants, with a remission rate of 85.7%. Higher baseline CDRS-R (p<0.001) and poorer functioning (p = 0.03) were the strongest discriminators between NO and GO. Higher baseline CDRS (p<0.001) and scores on the Mania Rating Scale (MRS) (p = 0.01) were the strongest discriminators between SLOW and GO. Other variables differentiating GO from both NO and from SLOW, were better baseline functioning, lower hopelessness, and lower family conflict. Both NO and SLOW showed increases on the MRS over time compared to GO (ps <= 0.04), and increasing MRS was strongly associated with lack of remission by 72 weeks (p = 0.02). Limitations: High rate of open treatment by the end of the follow-up period creates difficulty in drawing clear inferences about the long-term impact of initial randomization. Conclusion: Along with depressive severity, sub-syndromal manic symptoms, at baseline, and over time emerged as important predictors and correlates of poor outcome in this sample. Further research is needed on the treatment of severe depression, and on the assessment and management of sub-syndromal manic symptoms in treatment resistant depression. (C) 2011 Published by Elsevier B.V. C1 [Maalouf, Fadi T.] Amer Univ Beirut, Beirut, Lebanon. [Maalouf, Fadi T.; Porta, Giovanna; Birmaher, Boris; Ryan, Neal; Iyengar, Satish; Brent, David] Univ Pittsburgh, Pittsburgh, PA 15260 USA. [Vitiello, Benedetto] NIMH, Bethesda, MD 20892 USA. [Wagner, Karen D.] Univ Texas Galveston, Galveston, TX USA. [Asarnow, Joan Rosenbaum] Univ Calif Los Angeles, Los Angeles, CA USA. [Spirito, Anthony; Keller, Martin] Brown Univ, Providence, RI 02912 USA. [Shamseddeen, Wael] Rosalind Franklin Univ Med & Sci, N Chicago, IL USA. RP Brent, D (reprint author), Western Psychiat Inst & Clin, 3811 OHara St,Rm 311 Bellefield Towers, Pittsburgh, PA 15213 USA. EM brentda@upmc.edu FU Phillip Morris; Pfizer; National Institute of Mental Health: is a consultant for Schering Plough; Random House, Inc. (New Hope for Children and Teens with Bipolar Disorder); Lippincott Williams & Wilkins (Treating Child and Adolescent Depression); Guilford Press; UpToDate Psychiatry; NIMH [MH61835, MH6185E, MH61864, MH61869, MH61958, MH62014]; Advanced Center for Early-Onset Mood and Anxiety Disorders [MH66371]; Hikma pharmaceuticals; Biobehavioral Diagnostics; Eli Lilly; Forest Laboratories; GlaxoSmithKline; Somerset FX Dr. Asarnow reports receiving unrestricted research support from Phillip Morris and consulting on cognitive-behavior therapy and depression quality improvement.; Dr. Keller is currently a professor of Psychiatry and Human Behavior at Brown University School of Medicine, has been a consultant and received honoraria from CENEREX, Medtronic, Sierra Neuropharmaceuticals, and has received grant funding from Pfizer.; Dr. Birmaher is currently employed by the University of Pittsburgh and the University of Pittsburgh Medical Center/Western Psychiatric Institute and Clinic; has received research funding from the National Institute of Mental Health: is a consultant for Schering Plough; and has received royalties from Random House, Inc. (New Hope for Children and Teens with Bipolar Disorder) and Lippincott Williams & Wilkins (Treating Child and Adolescent Depression).; Dr. Brent is currently employed by the University of Pittsburgh, School of Medicine and the University of Pittsburgh Medical Center, Western Psychiatric Institute and Clinic; has received research support from the National Institute of Mental Health; receives royalties from Guilford Press; and serves as UpToDate Psychiatry Editor.; Funded by NIMH grants MH61835 (Pittsburgh); MH6185E (Galveston); MH61864 (UCLA); MH61869 (Portland); MH61958 (Dallas); and MH62014 (Brown), and the Advanced Center for Early-Onset Mood and Anxiety Disorders (MH66371, PI: David Brent, MD). The NIMH had no further role in study design; in the collection, analysis and interpretation of data; in the writing of the report; and in the decision to submit the paper for publication.; Dr. Maalouf is on the Speaker's Bureau of Eli Lilly and participated in a meeting sponsored by Hikma pharmaceuticals.; Dr. Emslie has received research support from Biobehavioral Diagnostics, Eli Lilly, Forest Laboratories, GlaxoSmithKline, and Somerset. He has served as a consultant for Biobehavioral Diagnostics, Eli Lilly, Forest Laboratories, GlaxoSmithKline, Pfizer, and Wyeth Pharmaceuticals. NR 45 TC 11 Z9 11 U1 1 U2 5 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0165-0327 J9 J AFFECT DISORDERS JI J. Affect. Disord. PD APR PY 2012 VL 138 IS 1-2 BP 86 EP 95 DI 10.1016/j.jad.2011.12.021 PG 10 WC Clinical Neurology; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 928IJ UT WOS:000302976100012 PM 22284022 ER PT J AU Valiengo, LL Soeiro-De-Souza, MG Marques, AH Moreno, DH Juruena, MF Andreazza, AC Gattaz, WF Machado-Vieira, R AF Valiengo, Leandro L. Soeiro-de-Souza, Marcio G. Marques, Andrea H. Moreno, Doris H. Juruena, Mario F. Andreazza, Ana Cristina Gattaz, Wagner F. Machado-Vieira, Rodrigo TI Plasma cortisol in first episode drug-naive mania: Differential levels in euphoric versus irritable mood SO JOURNAL OF AFFECTIVE DISORDERS LA English DT Article DE Cortisol; Bipolar disorder; Mania; Depression; Stress; Dimensional ID PITUITARY-ADRENAL AXIS; DEXAMETHASONE-SUPPRESSION TEST; BIPOLAR DISORDER; ADRENOCORTICAL FUNCTION; DEPRESSIVE SYMPTOMS; HORMONE TEST; STRESS; LITHIUM; SCHIZOPHRENIA; ILLNESS AB Background: Dysregulation of HPA axis has been widely described in subjects with bipolar disorder (BD), including changes in cortisol levels during mood episodes and euthymia. However, most of the studies were done with medicated BD patients with variable length of illness, which was shown to interfere on peripheral cortisol levels. Therefore, the present study aims to evaluate plasma cortisol levels in drug-naive BD subjects during the first manic episode, as well as investigate the relationship between plasma cortisol levels and manic symptomatology. Methods: Twenty-six drug-naive patients were enrolled meeting criteria for a first manic episode in bipolar I disorder. Severity of mania was assessed using the Young Mania Rating Scale (YMRS). The control group included 27 healthy subjects matched by age and gender. Cortisol was quantified using a direct radioimmunoassay. Results: Plasma cortisol levels were decreased during first manic episode compared to healthy controls. Higher cortisol levels were positively associated with the presence of irritability (dysphoria), while elated mania showed lower cortisol levels compared to controls. Limitation: Data including larger samples are lacking. Conclusion: Higher cortisol in dysphoric mania compared to predominantly elated/euphoric mania may indicate a clinical and neurobiological polymorphic phenomenon, potentially involving a higher biological sensitivity to stress in the presence of irritable mood. The present findings highlight the importance to add a dimensional approach to the traditional categorical diagnosis for future neurobiological studies in BD. (C) 2011 Elsevier B.V. All rights reserved. C1 [Valiengo, Leandro L.; Gattaz, Wagner F.; Machado-Vieira, Rodrigo] Univ Sao Paulo, Lab Neurosci, Inst & Dept Psychiat, BR-01060970 Sao Paulo, Brazil. [Soeiro-de-Souza, Marcio G.; Moreno, Doris H.] Univ Sao Paulo HC FMUSP, Mood Disorders Unit GRUDA, Dept & Inst Psychiat, Sch Med, Sao Paulo, Brazil. [Marques, Andrea H.] NIMH, Genet Epidemiol Branch, NIH, Bethesda, MD 20892 USA. [Juruena, Mario F.] Univ Sao Paulo, Dept Neurosci & Behav Sci, Ribeirao Preto, SP, Brazil. [Andreazza, Ana Cristina] Univ Toronto, Dept Psychiat, Toronto, ON, Canada. [Andreazza, Ana Cristina] Columbia Univ, Dept Epidemiol, Mailman Sch Publ Hlth, New York, NY USA. RP Machado-Vieira, R (reprint author), Univ Sao Paulo, Inst Psychiat, LIM 27,Rua Ovidio Pires de Campos,785, BR-01060970 Sao Paulo, Brazil. EM machadovieirar@gmail.com RI Gattaz, Wagner/C-4456-2012; MACHADO-VIEIRA, RODRIGO/D-8293-2012; Juruena, Mario/D-5571-2009; OI MACHADO-VIEIRA, RODRIGO/0000-0002-4830-1190; Juruena, Mario/0000-0001-8558-3396; Juruena, Mario F./0000-0002-4063-2278 FU Sao Paulo Research Foundation, Fapesp Brazil [2009/14891-9]; Fapesp [2009/14891-9]; Associacao Beneficente Alzira Denise Hertzog da Silva (ABADHS) FX This study was funded by Sao Paulo Research Foundation, Fapesp (2009/14891-9), Brazil.; We thank Fapesp (2009/14891-9) and Associacao Beneficente Alzira Denise Hertzog da Silva (ABADHS). NR 36 TC 10 Z9 10 U1 0 U2 2 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0165-0327 J9 J AFFECT DISORDERS JI J. Affect. Disord. PD APR PY 2012 VL 138 IS 1-2 BP 149 EP 152 DI 10.1016/j.jad.2011.11.046 PG 4 WC Clinical Neurology; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 928IJ UT WOS:000302976100020 PM 22305430 ER PT J AU Rosen, CJ Abrams, SA Aloia, JF Brannon, PM Clinton, SK Durazo-Arvizu, RA Gallagher, JC Gallo, RL Jones, G Kovacs, CS Manson, JE Mayne, ST Ross, AC Shapses, SA Taylor, CL AF Rosen, Clifford J. Abrams, Steven A. Aloia, John F. Brannon, Patsy M. Clinton, Steven K. Durazo-Arvizu, Ramon A. Gallagher, J. Christopher Gallo, Richard L. Jones, Glenville Kovacs, Christopher S. Manson, JoAnn E. Mayne, Susan T. Ross, A. Catharine Shapses, Sue A. Taylor, Christine L. TI IOM Committee Members Respond to Endocrine Society Vitamin D Guideline SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article ID D SUPPLEMENTATION; CALCIUM-ABSORPTION; BONE TURNOVER; D DEFICIENCY; WOMEN; PREECLAMPSIA; PREVENTION; PREVALENCE; PREGNANCY; MOTHERS AB In early 2011, a committee convened by the Institute of Medicine issued a report on the Dietary Reference Intakes for calcium and vitamin D. The Endocrine Society Task Force in July 2011 published a guideline for the evaluation, treatment, and prevention of vitamin D deficiency. Although these reports are intended for different purposes, the disagreements concerning the nature of the available data and the resulting conclusions have caused confusion for clinicians, researchers, and the public. In this commentary, members of the Institute of Medicine committee respond to aspects of The Endocrine Society guideline that are not well supported and in need of reconsideration. These concerns focus on target serum 25-hydroxyvitamin D levels, the definition of vitamin D deficiency, and the question of who constitutes a population at risk vs. the general population. (J Clin Endocrinol Metab 97: 1146-1152, 2012) C1 [Rosen, Clifford J.] Maine Med Ctr Res Inst, Scarborough, ME 04074 USA. Baylor Coll Med, Houston, TX 77030 USA. SUNY Stony Brook, Mineola, NY 11501 USA. Winthrop Univ Hosp, Mineola, NY 11501 USA. Cornell Univ, Ithaca, NY 14853 USA. Ohio State Univ, Columbus, OH 43210 USA. Loyola Univ Chicago, Maywood, IL 60153 USA. Creighton Univ, Med Ctr, Omaha, NE 68131 USA. Univ Calif San Diego, San Diego, CA 92161 USA. Queens Univ, Kingston, ON K7L 3N6, Canada. Mem Univ Newfoundland, St John, NF A1B 3V6, Canada. Harvard Univ, Sch Med, Boston, MA 02215 USA. Yale Univ, Sch Publ Hlth, New Haven, CT 06520 USA. Penn State Univ, University Pk, PA 16802 USA. Rutgers State Univ, New Brunswick, NJ 08901 USA. [Taylor, Christine L.] NIH, Off Dietary Supplements, Bethesda, MD 20892 USA. RP Rosen, CJ (reprint author), Maine Med Ctr Res Inst, 81 Res Dr, Scarborough, ME 04074 USA. EM crofen@gmail.com OI Gallo, Richard/0000-0002-1401-7861; Abrams, Steven/0000-0003-4972-9233; Kovacs, Christopher/0000-0002-5219-9993 FU NCI NIH HHS [R01 CA090214] NR 27 TC 189 Z9 194 U1 2 U2 18 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0021-972X EI 1945-7197 J9 J CLIN ENDOCR METAB JI J. Clin. Endocrinol. Metab. PD APR PY 2012 VL 97 IS 4 BP 1146 EP 1152 DI 10.1210/jc.2011-2218 PG 7 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 925US UT WOS:000302787800039 PM 22442278 ER PT J AU Harlow, SD Gass, M Hall, JE Lobo, R Maki, P Rebar, RW Sherman, S Sluss, PM de Villiers, TJ AF Harlow, Sioban D. Gass, Margery Hall, Janet E. Lobo, Roger Maki, Pauline Rebar, Robert W. Sherman, Sherry Sluss, Patrick M. de Villiers, Tobie J. CA STRAW 10 Collaborative Grp TI Executive Summary of the Stages of Reproductive Aging Workshop+10: Addressing the Unfinished Agenda of Staging Reproductive Aging SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article ID FOLLICLE-STIMULATING-HORMONE; ANTI-MULLERIAN HORMONE; EARLY MENOPAUSAL TRANSITION; POLYCYSTIC-OVARY-SYNDROME; MIDDLE-AGED WOMEN; REGULAR MENSTRUAL CYCLES; INHIBIN-B; ANTIMULLERIAN HORMONE; LONGITUDINAL CHANGES; DEPRESSIVE SYMPTOMS AB Objective: The aim of this article is to summarize the recommended updates to the 2001 Stages of Reproductive Aging Workshop (STRAW) criteria. The 2011 STRAW + 10 reviewed advances in understanding of the critical changes in hypothalamic-pituitary-ovarian function that occur before and after the final menstrual period. Methods: Scientists from five countries and multiple disciplines evaluated data from cohort studies of midlife women and in the context of chronic illness and endocrine disorders on change in menstrual, endocrine, and ovarian markers of reproductive aging including antimullerian hormone, inhibin-B, follicle-stimulating hormone, and antral follicle count. Modifications were adopted by consensus. Results: STRAW + 10 simplified bleeding criteria for the early and late menopausal transition, recommended modifications to criteria for the late reproductive stage (Stage -3) and the early postmenopause stage (Stage +1), provided information on the duration of the late transition (Stage-1) and early postmenopause (Stage + 1), and recommended application regardless of women's age, ethnicity, body size, or lifestyle characteristics. Conclusions: STRAW + 10 provides a more comprehensive basis for assessing reproductive aging in research and clinical contexts. Application of the STRAW + 10 staging system should improve comparability of studies of midlife women and facilitate clinical decision making. Nonetheless, important knowledge gaps persist, and seven research priorities are identified. (J Clin Endocrinol Metab 97: 1159-1168, 2012) C1 [Harlow, Sioban D.] Univ Michigan, Dept Epidemiol, Ann Arbor, MI 48109 USA. [Gass, Margery] N Amer Menopause Soc, Mayfield Hts, OH USA. [Hall, Janet E.] Harvard Univ, Sch Med, Dept Med, Endocrine Soc, Boston, MA USA. [Lobo, Roger] Columbia Univ, Dept Obstet & Gynecol, New York, NY USA. [Maki, Pauline] Univ Illinois, Dept Psychiat & Psychol, Chicago, IL USA. [Rebar, Robert W.] Amer Soc Reprod Med, Birmingham, AL USA. [Sherman, Sherry] NIA, Bethesda, MD 20892 USA. [Sluss, Patrick M.] Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. [de Villiers, Tobie J.] Int Menopause Soc, Cape Town, South Africa. RP Harlow, SD (reprint author), Univ Michigan, Dept Epidemiol, 1415 Washington Hts, Ann Arbor, MI 48109 USA. EM harlow@umich.edu FU National Institutes of Health (NIH); Department of Health and Human Services (DHHS), through the National Institute on Aging (NIA) [AG039961]; NIH Office of Research on Women's Health (ORWH); North American Menopause Society (NAMS); American Society for Reproductive Medicine (ASRM); International Menopause Society (IMS); Endocrine Society; National Institute on Aging (NIA); Eunice Kennedy Shriver National Institute of Child Health and Human Development(NICHD); National Institute on Mental Health (NIMH); National Institute of Allergy and Infectious Diseases (NIAID); National Institute on Drug Abuse (NIDA); Royal Ottawa Foundation for Mental Health; Mayo Clinic; Baycrest; Northwestern University; ASRM; Adcock Ingram; Pfizer; Servier FX This article is being simultaneously published in the journals Climacteric, Fertility and Sterility, the Journal of Clinical Endocrinology and Metabolism, and Menopause Funding/support: The Stages of Reproductive Aging Workshop (STRAW) + 10 had grant support from the National Institutes of Health (NIH), Department of Health and Human Services (DHHS), through the National Institute on Aging (NIA) (AG039961), and the NIH Office of Research on Women's Health (ORWH) as well as from The North American Menopause Society (NAMS), the American Society for Reproductive Medicine (ASRM), the International Menopause Society (IMS), and the Endocrine Society.; Financial disclosure/conflicts of interest: P.M.S. and S.S. declare no conflict of interest. M.G. receives salary support from The North American Menopause Society (NAMS). S.D.H. has grant support from the National Institute on Aging (NIA) and Eunice Kennedy Shriver National Institute of Child Health and Human Development(NICHD) and receives travel support from NAMS. J.E.H. has grant support from NIA and receives travel support from the Endocrine Society. R.L. is past president of the American Society for Reproductive Medicine (ASRM). P.M. receives grant support from the National Institute on Mental Health (NIMH), the NIA, the National Institute of Allergy and Infectious Diseases (NIAID), and the National Institute on Drug Abuse (NIDA); is on the Board of Trustees for NAMS; and has previously consulted for Noven Pharmaceuticals, received lecture fees from the Royal Ottawa Foundation for Mental Health, the Mayo Clinic, Baycrest, and Northwestern University and received travel support from the Society for Women's Health Research, the International Menopause Society, Pfizer, the Australasian Pacific Menopause Society, Virginia Commonwealth University Institute for Women's Health. R.W.R. receives salary support from ASRM. T.J.d.V. declares no direct conflict of interest as regards the submitted article but has in the past received consultancy fees from Adcock Ingram and Pfizer; speaker's fees from Servier; and travel support from Amgen, Pfizer, and Bayer. NR 90 TC 129 Z9 133 U1 0 U2 7 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0021-972X J9 J CLIN ENDOCR METAB JI J. Clin. Endocrinol. Metab. PD APR PY 2012 VL 97 IS 4 BP 1159 EP 1168 DI 10.1210/jc.2011-3362 PG 10 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 925US UT WOS:000302787800041 PM 22344196 ER PT J AU Semba, RD Sun, K Egan, JM Crasto, C Carlson, OD Ferrucci, L AF Semba, Richard D. Sun, Kai Egan, Josephine M. Crasto, Candace Carlson, Olga D. Ferrucci, Luigi TI Relationship of Serum Fibroblast Growth Factor 21 with Abnormal Glucose Metabolism and Insulin Resistance: The Baltimore Longitudinal Study of Aging SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article ID DENSITY-LIPOPROTEIN CHOLESTEROL; CHINESE SUBJECTS; FGF21; PLASMA; TOLERANCE; REGULATOR; OBESITY; CARBOHYDRATE; SENSITIVITY; MUSCLE AB Context: The relationship of fibroblast growth factor 21 (FGF21) with glucose metabolism and insulin resistance has not been well characterized in community-dwelling adults. Objective: The objective of the study was to examine the relationship of FGF21 with glucose metabolism and insulin resistance. Design: Serum FGF21, fasting plasma glucose (FPG), glucose tolerance, and insulin resistance were measured in a cross-sectional study, 2002-2007. Setting: The study was the Baltimore Longitudinal Study of Aging, a natural history cohort study of aging in community-dwelling men and women. Participants: Seven hundred adults, mean age 63.3 yr, participated in the study. Main Outcome Measures: FPG, 2-h plasma glucose, homeostasis model of insulin resistance, whole-body insulin sensitivity (Matsuda index), glucose area under the curve (AUC), and insulin AUC were measured. Results: Overall, the median (25th and 75th percentiles) FGF21 concentration was 225 (126, 370) pg/ml. The proportion of adults with normal, impaired, and diabetic FPG was 77.0, 21.4, and 1.6%, and those with normal, impaired, and diabetic 2-h plasma glucose was 76.7, 19.1, and 4.1%, respectively. Log serum FGF21 (picograms per milliliter), per 1 SD increase, was associated with an FPG (odds ratio 1.43, 95% confidence interval 1.15, 1.77, P = 0.001) and with 2-h plasma glucose (odds ratio 1.39, 95% confidence interval 1.12, 1.73, P = 0.003), in respective multivariate, ordered logistic regression models, adjusted for potential confounders. Serum FGF21 (picograms per milliliter) was associated with the homeostasis model of insulin resistance, the Matsuda index, glucose AUC, and insulin AUC (all P < 0.0001) in respective multivariable linear regression models adjusted for potential confounders. Conclusions: Higher serum FGF21 concentrations were associated with abnormal glucose metabolism and insulin resistance in community-dwelling adults. (J Clin Endocrinol Metab 97: 1375-1382, 2012) C1 [Semba, Richard D.; Sun, Kai; Crasto, Candace] Johns Hopkins Univ, Sch Med, Dept Ophthalmol, Baltimore, MD 21287 USA. [Egan, Josephine M.; Carlson, Olga D.] NIA, Clin Invest Lab, Baltimore, MD 21225 USA. [Ferrucci, Luigi] NIA, Longitudinal Studies Sect, Clin Res Branch, Baltimore, MD 21225 USA. RP Semba, RD (reprint author), Johns Hopkins Sch Med, Smith Bldg,400 N Broadway,M015, Baltimore, MD 21287 USA. EM rdsemba@jhmi.edu FU National Institutes of Health [R01 AG027012, R01 AG029148, R01 HL094507]; National Institute on Aging, National Institutes of Health FX This work was supported by National Institutes of Health Grants R01 AG027012, R01 AG029148, and R01 HL094507 and the Intramural Research Program, National Institute on Aging, National Institutes of Health. NR 27 TC 26 Z9 29 U1 0 U2 3 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0021-972X J9 J CLIN ENDOCR METAB JI J. Clin. Endocrinol. Metab. PD APR PY 2012 VL 97 IS 4 BP 1375 EP 1382 DI 10.1210/jc.2011-2823 PG 8 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 925US UT WOS:000302787800069 PM 22344195 ER PT J AU Almeida, MQ Azevedo, MF Xekouki, P Bimpaki, EI Horvath, A Collins, MT Karaviti, LP Jeha, GS Bhattacharyya, N Cheadle, C Watkins, T Bourdeau, I Nesterova, M Stratakis, CA AF Almeida, Madson Q. Azevedo, Monalisa F. Xekouki, Paraskevi Bimpaki, Eirini I. Horvath, Anelia Collins, Michael T. Karaviti, Lefkothea P. Jeha, George S. Bhattacharyya, Nisan Cheadle, Chris Watkins, Tonya Bourdeau, Isabelle Nesterova, Maria Stratakis, Constantine A. TI Activation of Cyclic AMP Signaling Leads to Different Pathway Alterations in Lesions of the Adrenal Cortex Caused by Germline PRKAR1A Defects versus Those due to Somatic GNAS Mutations SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article ID DAVID BIOINFORMATICS RESOURCES; LARGE GENE LISTS; ADRENOCORTICAL HYPERPLASIA; PHOSPHODIESTERASE 11A; MICRORNA SIGNATURE; KINASE; EXPRESSION; TUMORS; SUBUNIT; DISEASE AB Context: The overwhelming majority of benign lesions of the adrenal cortex leading to Cushing syndrome are linked to one or another abnormality of the cAMP or protein kinase pathway. PRKAR1A-inactivating mutations are responsible for primary pigmented nodular adrenocortical disease, whereas somatic GNAS activating mutations cause macronodular disease in the context of McCune-Albright syndrome, ACTH-independent macronodular hyperplasia, and, rarely, cortisol-producing adenomas. Objective and Design: The whole-genome expression profile (WGEP) of normal (pooled) adrenals, PRKAR1A-(3) and GNAS-mutant (3) was studied. Quantitative RT-PCR and Western blot were used to validate WGEP findings. Results: MAPK and p53 signaling pathways were highly overexpressed in all lesions against normal tissue. GNAS-mutant tissues were significantly enriched for extracellular matrix receptor interaction and focal adhesion pathways when compared with PRKAR1A-mutant (fold enrichment 3.5, P < 0.0001 and 2.1, P < 0.002, respectively). NFKB, NFKBIA, and TNFRSF1A were higher inGNAS-mutant tumors (P < 0.05). Genes related to the Wntsignaling pathway(CCND1, CTNNB1, LEF1, LRP5, WISP1, and WNT3) were overexpressed in PRKAR1A-mutant lesions. Conclusion: WGEP analysis revealed that not all cAMP activation is the same: adrenal lesions harboring PRKAR1A or GNAS mutations share the downstream activation of certain oncogenic signals (such as MAPK and some cell cycle genes) but differ substantially in their effects on others. (J Clin Endocrinol Metab 97: E687-E693, 2012) C1 [Almeida, Madson Q.; Azevedo, Monalisa F.; Xekouki, Paraskevi; Bimpaki, Eirini I.; Horvath, Anelia; Bourdeau, Isabelle; Nesterova, Maria; Stratakis, Constantine A.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Sect Endocrinol & Genet, Program Dev Endocrinol & Genet PDEGEN, Bethesda, MD 20892 USA. [Stratakis, Constantine A.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Pediat Endocrinol Interinst Training Program, Bethesda, MD 20892 USA. [Collins, Michael T.; Bhattacharyya, Nisan] Natl Inst Dent & Craniofacial Res, Skeletal Clin Studies Unit, Craniofacial & Skeletal Dis Branch, NIH, Bethesda, MD 20892 USA. [Karaviti, Lefkothea P.; Jeha, George S.] Texas Childrens Hosp, Baylor Coll Med, Dept Pediat Endocrinol & Metab, Houston, TX 77030 USA. [Cheadle, Chris; Watkins, Tonya] Johns Hopkins Univ, Sch Med, Div Allergy & Clin Immunol, Baltimore, MD 21224 USA. [Bourdeau, Isabelle] Ctr Hosp Univ Montreal, Div Endocrinol, Dept Med, Res Ctr, Montreal, PQ H3T 1C5, Canada. RP Stratakis, CA (reprint author), Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Sect Endocrinol & Genet, Program Dev Endocrinol & Genet, CRC,NIH, Bldg 10,Room 1-3330,10 Ctr Dr,MSC1103, Bethesda, MD 20892 USA. EM stratakc@mail.nih.gov RI Levesque, Isabelle/A-1899-2012; OI Jeha, George/0000-0002-3531-5059 FU National Institutes of Health, Eunice Kennedy Shriver National Institute of Child Health and Human Development [Z01-HD-000642-04] FX This work was supported by Intramural Project Grant Z01-HD-000642-04 from the National Institutes of Health, Eunice Kennedy Shriver National Institute of Child Health and Human Development (to C.A.S.). NR 26 TC 24 Z9 25 U1 0 U2 5 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0021-972X J9 J CLIN ENDOCR METAB JI J. Clin. Endocrinol. Metab. PD APR PY 2012 VL 97 IS 4 BP E687 EP E693 DI 10.1210/jc.2011-3000 PG 7 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 925US UT WOS:000302787800026 PM 22259056 ER PT J AU Weisbrod, AB Kitano, M Gesuwan, K Millo, C Herscovitch, P Nilubol, N Linehan, WM Kebebew, E AF Weisbrod, Allison B. Kitano, Mio Gesuwan, Krisana Millo, Corina Herscovitch, Peter Nilubol, Naris Linehan, W. Marston Kebebew, Electron TI Clinical Utility of Functional Imaging with F-18-FDOPA in Von Hippel-Lindau Syndrome SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article ID POSITRON-EMISSION-TOMOGRAPHY; NEUROENDOCRINE TUMORS; ENDOCRINE TUMORS; PET; DISEASE; PHEOCHROMOCYTOMA; SCINTIGRAPHY AB Context: Von Hippel-Lindau (VHL) syndrome is an inherited cancer syndrome in which patients are at risk of developing multiple tumors in different organs. 6-L-F-18-fluorodihydroxyphenylalanine (F-18-FDOPA) positron emission tomography (PET) is a relatively new metabolic imaging tracer proposed for the use of localizing sites of neuroendocrine tumors. There are limited data on the clinical utility of using F-18-FDOPA PET for identifying neuroendocrine tumors in a high-risk population such as VHL. Objective: The aim of this prospective study was to evaluate the clinical utility of F-18-FDOPA PET in patients with VHL-related tumors. Design: Radiological findings were prospectively collected from four imaging modalities: computed tomography, magnetic resonance imaging (MRI), F-18-fluorodeoxyglucose PET, and (18)FFDOPA PET. F-18-FDOPA PET findings were compared with those from other imaging modalities, as well as with clinical and laboratory data, and pathology findings if patients underwent an operation. Results: In 52 patients with VHL, 390 lesions were identified by computed tomography (n = 139), MRI (n = 117), F-18-fluorodeoxyglucose PET (n = 94), and F-18-FDOPA PET (n = 40). F-18-FDOPA PET identified 20 pancreatic and 20 extrapancreatic tumors, including lesions in the adrenal gland (n = 11), kidney (n = 3), liver (n = 4), lung (n = 1), and cervical paraganglioma (n = 1). These tumor sites were not seen by conventional imaging studies in 9.6% of patients and 4.4% of lesions. Seven of eight patients who had an F-18-FDOPA PET-positive lesion underwent resection, and pathology showed a neuroendocrine tumor. Four of 10 patients with positive adrenal uptake had elevated catecholamine levels, and six of 10 patients had a discrete mass on axial imaging. Conclusions: F-18-FDOPA PET is a useful complementary imaging study to detect neuroendocrine tumors in patients with VHL undergoing surveillance, especially in those suspected to have adrenal pheochromocytoma or unusual ectopic locations. (J Clin Endocrinol Metab 97: E613-E617, 2012) C1 [Kebebew, Electron] NCI, Endocrine Oncol Sect, Surg Branch, NIH,Clin Res Ctr, Bethesda, MD 20892 USA. [Millo, Corina; Herscovitch, Peter] NIH, Dept Nucl Med, Positron Emiss Tomog Imaging Sect, Bethesda, MD 20892 USA. [Linehan, W. Marston] NCI, Urol Oncol Branch, NIH, Bethesda, MD 20892 USA. RP Kebebew, E (reprint author), NCI, Endocrine Oncol Sect, Surg Branch, NIH,Clin Res Ctr, Bldg 10-CRC,Room 3-3940,10 Ctr Dr,MSC 1201, Bethesda, MD 20892 USA. EM kebebewe@mail.nih.gov FU Center for Cancer Research, National Cancer Institute, National Institutes of Health FX This research was supported by the intramural research program of the Center for Cancer Research, National Cancer Institute, National Institutes of Health. NR 19 TC 6 Z9 6 U1 1 U2 4 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0021-972X J9 J CLIN ENDOCR METAB JI J. Clin. Endocrinol. Metab. PD APR PY 2012 VL 97 IS 4 BP E613 EP E617 DI 10.1210/jc.2011-2626 PG 5 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 925US UT WOS:000302787800013 PM 22259055 ER PT J AU Newbold, RR AF Newbold, R. R. TI Prenatal exposure to diethylstilbestrol and long-term impact on the breast and reproductive tract in humans and mice SO JOURNAL OF DEVELOPMENTAL ORIGINS OF HEALTH AND DISEASE LA English DT Review DE breast cancer; critical windows; epigenetics; fibroids; hormonal carcinogenesis ID MAMMARY-GLAND DEVELOPMENT; ENDOCRINE-DISRUPTING CHEMICALS; BISPHENOL-A ALTERS; DEVELOPMENTAL EXPOSURE; PERINATAL EXPOSURE; CANCER-RISK; IN-UTERO; ESTROGEN-RECEPTORS; GENE-EXPRESSION; NEONATAL MICE AB The term 'developmental origins of health and disease' (DOHaD) originally referred to delayed effects of altered maternal factors (e.g. smoking or poor nutrition) on the developing offspring, but it now also encompasses early life exposure to environmental chemicals, which can cause an unhealthy prenatal environment that endangers the fetus and increases its susceptibility to disease later in life. Prenatal exposure to the pharmaceutical diethylstilbestrol (DES) is a well-known DOHaD example as it was associated in the 1970s with vaginal cancer in daughters who were exposed to this potent synthetic estrogen before birth. Subsequently, numerous long-term effects have been described in breast and reproductive tissues of DES-exposed humans and experimental animals. Data reviewed suggest that the prenatal DES-exposed population should continue to be monitored for potential-increased disease risks as they age. Knowledge of sensitive developmental periods, and the mechanisms of DES-induced toxicities, provides useful information in predicting potential adverse effects of other environmental estrogens. C1 NIEHS, Natl Toxicol Program, NIH, DHHS, Res Triangle Pk, NC 27709 USA. RP Newbold, RR (reprint author), NIEHS, Natl Toxicol Program, NIH, DHHS, POB 12233,Mail Drop K2-15, Res Triangle Pk, NC 27709 USA. EM newbold1@niehs.nih.gov NR 72 TC 4 Z9 4 U1 1 U2 15 PU CAMBRIDGE UNIV PRESS PI CAMBRIDGE PA EDINBURGH BLDG, SHAFTESBURY RD, CB2 8RU CAMBRIDGE, ENGLAND SN 2040-1744 J9 J DEV ORIG HLTH DIS JI J. Dev. Orig. Health Dis. PD APR PY 2012 VL 3 IS 2 BP 73 EP 82 DI 10.1017/S2040174411000754 PG 10 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 929KQ UT WOS:000303061700002 PM 25101917 ER PT J AU Schisler, RE Groninger, H Rosielle, DA AF Schisler, Randall E. Groninger, Hunter Rosielle, Drew A. TI Counseling Patients on Side Effects and Driving When Starting Opioids #248 SO JOURNAL OF PALLIATIVE MEDICINE LA English DT Editorial Material ID CANCER PAIN C1 [Groninger, Hunter] NIH, Pain & Palliat Care Serv, Ctr Clin, Bethesda, MD 20892 USA. [Rosielle, Drew A.] Univ Minnesota, Palliat Care Program, Sch Med, Minneapolis, MN 55455 USA. [Rosielle, Drew A.] Med Coll Wisconsin, End Life Palliat Educ Resource Ctr, Milwaukee, WI USA. RP Groninger, H (reprint author), NIH, Pain & Palliat Care Serv, Ctr Clin, Bldg 10,Room 2-1733, Bethesda, MD 20892 USA. EM hunter.groninger@nih.gov OI Rosielle, Drew/0000-0003-3942-3791 NR 11 TC 3 Z9 3 U1 0 U2 0 PU MARY ANN LIEBERT INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1096-6218 J9 J PALLIAT MED JI J. Palliat. Med. PD APR PY 2012 VL 15 IS 4 BP 484 EP 485 DI 10.1089/jpm.2012.9596 PG 2 WC Health Care Sciences & Services SC Health Care Sciences & Services GA 926TM UT WOS:000302854700019 PM 22500484 ER PT J AU Greenberg, SJ AF Greenberg, Stephen J. TI The Plague in Print: Essential Elizabethan Sources, 1558-1603 SO JOURNAL OF THE HISTORY OF MEDICINE AND ALLIED SCIENCES LA English DT Book Review C1 [Greenberg, Stephen J.] NIH, Hist Med Div, Natl Lib Med, US Dept HHS, Bethesda, MD 20894 USA. RP Greenberg, SJ (reprint author), NIH, Hist Med Div, Natl Lib Med, US Dept HHS, Bethesda, MD 20894 USA. NR 1 TC 0 Z9 0 U1 0 U2 1 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0022-5045 J9 J HIST MED ALL SCI JI J. Hist. Med. Allied Sci. PD APR PY 2012 VL 67 IS 2 BP 328 EP 329 DI 10.1093/jhmas/jrr052 PG 2 WC Health Care Sciences & Services; History & Philosophy Of Science SC Health Care Sciences & Services; History & Philosophy of Science GA 927FH UT WOS:000302892000006 ER PT J AU Reznick, JS AF Reznick, Jeffrey S. TI War, Politics, and Philanthropy: The History of Rehabilitation Medicine SO JOURNAL OF THE HISTORY OF MEDICINE AND ALLIED SCIENCES LA English DT Book Review C1 [Reznick, Jeffrey S.] NIH, Hist Med Div, US Natl Lib Med, Bethesda, MD 20894 USA. RP Reznick, JS (reprint author), NIH, Hist Med Div, US Natl Lib Med, Bethesda, MD 20894 USA. NR 1 TC 0 Z9 0 U1 1 U2 1 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0022-5045 J9 J HIST MED ALL SCI JI J. Hist. Med. Allied Sci. PD APR PY 2012 VL 67 IS 2 BP 335 EP 337 DI 10.1093/jhmas/jrr062 PG 3 WC Health Care Sciences & Services; History & Philosophy Of Science SC Health Care Sciences & Services; History & Philosophy of Science GA 927FH UT WOS:000302892000010 ER PT J AU Wolfe, LL Kocisko, DA Caughey, B Miller, MW AF Wolfe, Lisa L. Kocisko, David A. Caughey, Byron Miller, Michael W. TI Assessment of Prospective Preventive Therapies for Chronic Wasting Disease in Mule Deer SO JOURNAL OF WILDLIFE DISEASES LA English DT Article ID PRION PROTEIN-FORMATION; SCRAPIE; INHIBITION AB We compared prion infection rates among mule deer (Odocoileus hemionus) receiving pentosan polysulfate, tannic acid, tetracycline HCl, or no treatment 14 days before to 14 days after (dpi) oral inoculation with tonsil tissue homogenate. All deer were infected, but the rapid disease course (230-603 dpi) suggested our challenge was overwhelming. C1 [Wolfe, Lisa L.; Miller, Michael W.] Wildlife Res Ctr, Colorado Div Wildlife, Ft Collins, CO 80526 USA. [Kocisko, David A.; Caughey, Byron] NIAID, Persistent Viral Dis Lab, Rocky Mt Labs, NIH, Hamilton, MT 59840 USA. RP Wolfe, LL (reprint author), Wildlife Res Ctr, Colorado Div Wildlife, 317 W Prospect Rd, Ft Collins, CO 80526 USA. EM lisa.wolfe@state.co.us FU Colorado Division of Wildlife; National Institutes of Health FX We thank the Colorado Division of Wildlife and the National Institutes of Health for support, and T. M. Davis, E. S. Williams, and many others for their assistance over the course of this study. NR 15 TC 1 Z9 1 U1 0 U2 4 PU WILDLIFE DISEASE ASSOC, INC PI LAWRENCE PA 810 EAST 10TH ST, LAWRENCE, KS 66044-8897 USA SN 0090-3558 J9 J WILDLIFE DIS JI J. Wildl. Dis. PD APR PY 2012 VL 48 IS 2 BP 530 EP 533 PG 4 WC Veterinary Sciences SC Veterinary Sciences GA 922ZZ UT WOS:000302589000038 PM 22493139 ER PT J AU Vatsalya, V Coe, MA Ramchandani, VA Karch, R AF Vatsalya, Vatsalya Coe, Marion A. Ramchandani, Vijay A. Karch, Robert TI Sex and Age Variations in Quality of Life Indices Among Alcohol Drinking Population SO JOURNAL OF WOMENS HEALTH LA English DT Meeting Abstract C1 [Vatsalya, Vatsalya; Karch, Robert] Amer Univ DC, Washington, DC USA. [Vatsalya, Vatsalya; Coe, Marion A.; Ramchandani, Vijay A.] NIAAA, SHP LCTS, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 2 PU MARY ANN LIEBERT INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1540-9996 J9 J WOMENS HEALTH JI J. Womens Health PD APR PY 2012 VL 21 IS 4 MA P139 BP 53 EP 53 PG 1 WC Public, Environmental & Occupational Health; Medicine, General & Internal; Obstetrics & Gynecology; Women's Studies SC Public, Environmental & Occupational Health; General & Internal Medicine; Obstetrics & Gynecology; Women's Studies GA 926UE UT WOS:000302856600140 ER PT J AU Grkovic, L Baird, K Steinberg, SM Williams, KM Pulanic, D Cowen, EW Mitchell, SA Hakim, FT Martires, KJ Avila, DN Taylor, TN Salit, RB Rowley, SD Zhang, D Fowler, DH Bishop, MR Gress, RE Pavletic, SZ AF Grkovic, L. Baird, K. Steinberg, S. M. Williams, K. M. Pulanic, D. Cowen, E. W. Mitchell, S. A. Hakim, F. T. Martires, K. J. Avila, D. N. Taylor, T. N. Salit, R. B. Rowley, S. D. Zhang, D. Fowler, D. H. Bishop, M. R. Gress, R. E. Pavletic, S. Z. TI Clinical laboratory markers of inflammation as determinants of chronic graft-versus-host disease activity and NIH global severity SO LEUKEMIA LA English DT Article DE chronic graft-versus-host disease; inflammation; activity; CRP; platelets ID C-REACTIVE PROTEIN; STEM-CELL TRANSPLANTATION; BONE-MARROW-TRANSPLANTATION; CONSENSUS DEVELOPMENT PROJECT; WORKING GROUP-REPORT; NEPHROTIC SYNDROME; RHEUMATOID-ARTHRITIS; SYSTEMIC-SCLEROSIS; CHRONIC GVHD; INTERLEUKIN-6 AB Chronic graft-versus-host disease (cGVHD) remains a major cause of non-relapse morbidity and mortality after allogeneic hematopoietic stem cell transplantation. Currently there are no accepted measures of cGVHD activity to aid in clinical management and disease staging. We analyzed clinical markers of inflammation in the sera of patients with established cGVHD and correlated those with definitions of disease activity. In all, 189 adults with cGVHD (33% moderate and 66% severe according to National Institutes of Health (NIH) global scoring) were consecutively enrolled onto a cross-sectional prospective cGVHD natural history study. At the time of evaluation, 80% were receiving systemic immunosuppression and failed a median of four prior systemic therapies (PST) for their cGVHD. Lower albumin (P < 0.0001), higher C-reactive protein (P = 0.043), higher platelets (P = 0.030) and higher number of PST (P < 0.0001) were associated with active disease defined as clinician's intention to intensify or alter systemic therapy due to the lack of response. Higher platelet count (P = 0.021) and higher number of PST (P < 0.0001) were associated with more severe diseased defined by NIH global score. This study identified common laboratory indicators of inflammation that can serve as markers of cGVHD activity and severity. Leukemia (2012) 26, 633-643; doi:10.1038/leu.2011.254; published online 18 October 2011 C1 [Grkovic, L.; Williams, K. M.; Hakim, F. T.; Avila, D. N.; Taylor, T. N.; Salit, R. B.; Fowler, D. H.; Bishop, M. R.; Gress, R. E.; Pavletic, S. Z.] NCI, Graft Versus Host & Autoimmun Unit, Expt Transplantat & Immunol Branch, NIH, Bethesda, MD 20892 USA. [Grkovic, L.; Pulanic, D.] Clin Hosp Ctr Zagreb, Dept Internal Med, Div Hematol, Zagreb, Croatia. [Baird, K.] NCI, Pediat Oncol Branch, NIH, Bethesda, MD 20892 USA. [Steinberg, S. M.; Zhang, D.] NCI, Biostat & Data Management Sect, Off Clin Director, Ctr Canc Res,NIH, Bethesda, MD 20892 USA. [Cowen, E. W.; Martires, K. J.] NCI, Dermatol Branch, NIH, Bethesda, MD 20892 USA. [Mitchell, S. A.] NCI, Div Canc Control & Populat Sci, NIH, Bethesda, MD 20892 USA. [Rowley, S. D.] Hackensack Univ, Med Ctr, John Theurer Canc Ctr, Hackensack, NJ USA. RP Pavletic, SZ (reprint author), NCI, Graft Versus Host & Autoimmun Unit, Expt Transplantat & Immunol Branch, NIH, 10 Ctr Dr,Bldg 10,Room CRC 3-3330, Bethesda, MD 20892 USA. EM pavletis@mail.nih.gov FU National Institutes of Health, Center for Cancer Research and National Cancer Institute; Clinical Research Training Program; NIH; Pfizer Inc. FX This study was supported by the Intramural Research Program of the National Institutes of Health, Center for Cancer Research and National Cancer Institute. We thank Dr N Rehak, Dr Katherine Calvo and Dr Irina Maric, Department of Laboratory Medicine, Clinical Center, NIH for providing the clinical laboratory methods information. Lana Grkovic is a participant in the NIH Graduate Partnership Program and a post-graduate student at the Division of Hematology, University of Zagreb, School of Medicine, Zagreb, Croatia. Kathryn J Martires was supported by the Clinical Research Training Program, a public-private partnership supported jointly by the NIH and Pfizer Inc. (via a grant to the Foundation for NIH from Pfizer Inc.). NR 52 TC 21 Z9 21 U1 1 U2 3 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0887-6924 J9 LEUKEMIA JI Leukemia PD APR PY 2012 VL 26 IS 4 BP 633 EP 643 DI 10.1038/leu.2011.254 PG 11 WC Oncology; Hematology SC Oncology; Hematology GA 925UX UT WOS:000302788300009 PM 22005783 ER PT J AU Calado, RT Cooper, JN Padilla-Nash, HM Sloand, EM Wu, CO Scheinberg, P Ried, T Young, NS AF Calado, R. T. Cooper, J. N. Padilla-Nash, H. M. Sloand, E. M. Wu, C. O. Scheinberg, P. Ried, T. Young, N. S. TI Short telomeres result in chromosomal instability in hematopoietic cells and precede malignant evolution in human aplastic anemia SO LEUKEMIA LA English DT Article DE telomere; chromosome instability; aplastic anemia; myelodysplasia; cancer ID DYSKERATOSIS-CONGENITA; CYTOGENETIC ABNORMALITIES; CANCER; DYSFUNCTION; LENGTH; MICE; MUTATIONS; GENE; ASSOCIATION; COMPONENT AB In cell and animal models, telomere erosion promotes chromosomal instability via breakage-fusion-bridge cycles, contributing to the early stages of tumorigenesis. However, evidence involving short telomeres in cancer development in humans is scarce, epidemiological and indirect. Here we directly implicate telomere shortening as a critical molecular event for malignant evolution in aplastic anemia (AA). Patients' telomere lengths at diagnosis of AA, while comparable to age-matched controls, inversely correlated with the probability of developing a cytogenetically abnormal clone. A significantly increased number of telomere signal-free chromosomal ends and chromosomal numerical and structural abnormalities were observed in bone marrow cells of patients with shorter telomeres in comparison with patients with longer telomeres and healthy subjects. The proportion of monosomy-7 cells in the bone marrow at diagnosis of AA inversely correlated with telomere length, years before the emergence of an autonomous and clinically detectable abnormal clone. Marrow cells of clinically healthy individuals carrying loss-of-function telomerase mutations and with extremely short telomeres also showed chromosomal instability in vitro. These results provide the first clinical direct evidence in humans that short telomeres in hematopoietic cells are dysfunctional, mediate chromosomal instability and predispose to malignant transformation in a human disease. Leukemia (2012) 26, 700-707; doi:10.1038/leu.2011.272; published online 18 October 2011 C1 [Calado, R. T.; Cooper, J. N.; Sloand, E. M.; Scheinberg, P.; Young, N. S.] NHLBI, Hematol Branch, NIH, Bethesda, MD 20892 USA. [Cooper, J. N.] NIH, Clin Res Training Program, Bethesda, MD 20892 USA. [Padilla-Nash, H. M.; Ried, T.] NCI, Genet Branch, NIH, Bethesda, MD 20892 USA. [Wu, C. O.] NHLBI, Off Biostat Res, NIH, Bethesda, MD 20892 USA. RP Calado, RT (reprint author), Univ Sao Paulo, Sch Med, Dept Internal Med, Hematol Lab,Subsolo HCRP, Av Bandeirantes 3900,Bloco G, BR-14049900 Ribeirao Preto, SO, Brazil. EM calador@nhlbi.nih.gov RI Calado, Rodrigo/G-2619-2011; OI Scheinberg, Phillip/0000-0002-9047-4538 FU NIH; Pfizer FX This work was entirely supported by the NIH Intramural Research Program. Dr Cooper's research year was made possible through the Clinical Research Training Program (CRTP), a public-private partnership supported jointly by the NIH and Pfizer (grant to the Foundation for NIH from Pfizer). EMS is deceased. We are grateful to Olga Nunez, RN and Barbara Weinstein, RN for patient care and sample collection. NR 41 TC 33 Z9 39 U1 0 U2 5 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0887-6924 J9 LEUKEMIA JI Leukemia PD APR PY 2012 VL 26 IS 4 BP 700 EP 707 DI 10.1038/leu.2011.272 PG 8 WC Oncology; Hematology SC Oncology; Hematology GA 925UX UT WOS:000302788300016 PM 22005790 ER PT J AU Landgren, O Ma, W Kyle, RA Rajkumar, SV Korde, N Albitar, M AF Landgren, O. Ma, W. Kyle, R. A. Rajkumar, S. V. Korde, N. Albitar, M. TI Polymorphism of the erythropoietin gene promotor and the development of myelodysplastic syndromes subsequent to multiple myeloma SO LEUKEMIA LA English DT Letter ID ACUTE-LEUKEMIA; MELPHALAN; CHEMOTHERAPY; ASSOCIATION; NEOPLASMS C1 [Landgren, O.; Korde, N.] NCI, Multiple Myeloma Sect, Med Oncol Branch, Ctr Canc Res,NIH, Bethesda, MD 20892 USA. [Ma, W.; Albitar, M.] Quest Diagnost Nicols Inst, Dept Hematol Oncol, San Juan Capistrano, CA USA. [Kyle, R. A.; Rajkumar, S. V.] Mayo Clin, Div Hematol, Rochester, MN USA. RP Landgren, O (reprint author), NCI, Multiple Myeloma Sect, Med Oncol Branch, Ctr Canc Res,NIH, Bethesda, MD 20892 USA. EM landgreo@mail.nih.gov OI Rajkumar, S. Vincent/0000-0002-5862-1833 NR 9 TC 7 Z9 7 U1 0 U2 2 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0887-6924 J9 LEUKEMIA JI Leukemia PD APR PY 2012 VL 26 IS 4 BP 844 EP 845 DI 10.1038/leu.2011.262 PG 3 WC Oncology; Hematology SC Oncology; Hematology GA 925UX UT WOS:000302788300037 PM 21926963 ER PT J AU Kapetanovic, IM AF Kapetanovic, Izet M. TI Comment on Resveratrol in human cancer chemoprevention- choosing the right' dose' SO MOLECULAR NUTRITION & FOOD RESEARCH LA English DT Letter C1 NCI, NIH, Canc Prevent Div, Chemoprevent Agent Dev Res Grp, Bethesda, MD 20892 USA. RP Kapetanovic, IM (reprint author), NCI, NIH, Canc Prevent Div, Chemoprevent Agent Dev Res Grp, Bethesda, MD 20892 USA. NR 1 TC 0 Z9 0 U1 0 U2 3 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1613-4125 J9 MOL NUTR FOOD RES JI Mol. Nutr. Food Res. PD APR PY 2012 VL 56 IS 4 BP 523 EP 523 DI 10.1002/mnfr.2012700024 PG 1 WC Food Science & Technology SC Food Science & Technology GA 924WH UT WOS:000302721500001 PM 22495980 ER PT J AU Waubant, E Pelletier, D Mass, M Cohen, JA Kita, M Cross, A Bar-Or, A Vollmer, T Racke, M Stuve, O Schwid, S Goodman, A Kachuck, N Preiningerova, J Weinstock-Guttman, B Calabresi, PA Miller, A Mokhtarani, M Ikle, D Murphy, S Kopetskie, H Ding, L Rosenberg, E Spencer, C Zamvil, SS AF Waubant, E. Pelletier, D. Mass, M. Cohen, J. A. Kita, M. Cross, A. Bar-Or, A. Vollmer, T. Racke, M. Stueve, O. Schwid, S. Goodman, A. Kachuck, N. Preiningerova, J. Weinstock-Guttman, B. Calabresi, P. A. Miller, A. Mokhtarani, M. Ikle, D. Murphy, S. Kopetskie, H. Ding, L. Rosenberg, E. Spencer, C. Zamvil, S. S. CA ITN STAyCIS Study Grp TI Randomized controlled trial of atorvastatin in clinically isolated syndrome The STAyCIS study SO NEUROLOGY LA English DT Article ID REMITTING MULTIPLE-SCLEROSIS; INTRAMUSCULAR INTERFERON BETA-1A; SIMVASTATIN TREATMENT; STATINS; THERAPY; CELLS; AUTOIMMUNITY; COMBINATION; PARALYSIS; DISEASE AB Objective: To test efficacy and safety of atorvastatin in subjects with clinically isolated syndrome (CIS). Methods: Subjects with CIS were enrolled in a phase II, double-blind, placebo-controlled, 14-center randomized trial testing 80 mg atorvastatin on clinical and brain MRI activity. Brain MRIs were performed quarterly. The primary endpoint (PEP) was development of >= 3new T2 lesions, or one clinical relapse within 12months. Subjects meeting the PEP were offered additional weekly interferon beta-1a (IFN beta-1a). Results: Due to slow recruitment, enrollment was discontinued after 81 of 152 planned subjects with CIS were randomized and initiated study drug. Median (interquartile range) numbers of T2 and gadolinium-enhancing (Gd) lesions were 15.0(22.0) and 0.0 (0.0) at baseline. A total of 53.1% of atorvastatin recipients (n = 26/49) met PEP compared to 56.3% of placebo recipients (n = 18/ 32) (p = 0.82). Eleven atorvastatin subjects (22.4%) and 7 placebo subjects (21.9%) met the PEP by clinical criteria. Proportion of subjects who did not develop new T2 lesions up to month 12 or to starting IFN beta-1a was 55.3% in the atorvastatin and 27.6% in the placebo group (p = 0.03). Likelihood of remaining free of new T2 lesions was significantly greater in the atorvastatin group compared with placebo (odds ratio [OR] = 4.34, p = 0.01). Likelihood of remaining free of Gd lesions tended to be higher in the atorvastatin group (OR = 2.72, p = 0.11). Overall, atorvastatin was well tolerated. No clear antagonistic effect of atorvastatin plus IFN beta-1a was observed on MRI measures. Conclusion: Atorvastatin treatment significantly decreased development of new brain MRI T2 lesion activity, although it did not achieve the composite clinical and imaging PEP. Classification of Evidence: This study provided Class II evidence that atorvastatin did not reduce the proportion of patients with CIS meeting imaging and clinical criteria for starting immunomodulating therapy after 12 months, compared to placebo. In an analysis of a secondary endpoint (Class III), atorvastatin was associated with a reduced risk for developing new T2 lesions. Neurology (R) 2012;78:1171-1178 C1 [Waubant, E.; Pelletier, D.; Spencer, C.; Zamvil, S. S.] Univ Calif San Francisco, San Francisco, CA 94143 USA. [Mass, M.] Oregon Hlth & Sci Univ, Portland, OR 97201 USA. [Cohen, J. A.] Cleveland Clin Fdn, Cleveland, OH 44195 USA. [Kita, M.] Virginia Mason MS Ctr, Seattle, WA USA. [Cross, A.] Washington Univ, MS Ctr, St Louis, MO USA. [Bar-Or, A.] McGill Univ, Montreal Neurol Inst, Montreal, PQ, Canada. [Vollmer, T.] Barrow Neurol Inst, Phoenix, AZ 85013 USA. [Racke, M.; Stueve, O.] Univ Texas SW Med Ctr Dallas, Dallas, TX 75390 USA. [Schwid, S.; Goodman, A.] Univ Rochester, Rochester, NY USA. [Kachuck, N.] Univ So Calif, Keck Sch Med, MS Ctr, Los Angeles, CA 90033 USA. [Preiningerova, J.] Yale MS Res Ctr, New Haven, CT USA. [Weinstock-Guttman, B.] Jacobs Neurol Inst, Buffalo, NY USA. [Calabresi, P. A.] Johns Hopkins Univ, Baltimore, MD USA. [Miller, A.] Mt Sinai Sch Med, New York, NY USA. [Mokhtarani, M.] Immune Tolerance Network, Seattle, WA USA. [Ikle, D.; Murphy, S.; Kopetskie, H.] Rho Inc, Chapel Hill, NC USA. [Ding, L.; Rosenberg, E.] NIAID, Bethesda, MD 20892 USA. RP Zamvil, SS (reprint author), Univ Calif San Francisco, San Francisco, CA 94143 USA. EM zamvil@ucsf.neuroimmunol.org FU Immune Tolerance Network [ITN020AI, N01-AI-15416]; National Institute of Allergy and Infectious Diseases; Nancy Davis Foundation; National Institutes of Health [RO1 AI059709]; Maisin Foundation FX This research was performed as a project of the Immune Tolerance Network (ITN020AI, ITN contract number N01-AI-15416), a clinical research consortium sponsored by the National Institute of Allergy and Infectious Diseases. Pfizer provided atorvastatin, placebo, and grant support. Biogen Idec provided IFN beta-1a IM and grant support. E.W. is also supported by the Nancy Davis Foundation. S.S.Z. was also supported for this study by the National Institutes of Health (RO1 AI059709) and the Maisin Foundation. NR 23 TC 23 Z9 23 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0028-3878 J9 NEUROLOGY JI Neurology PD APR PY 2012 VL 78 IS 15 BP 1171 EP 1178 PG 8 WC Clinical Neurology SC Neurosciences & Neurology GA 925WH UT WOS:000302792200014 PM 22459680 ER PT J AU Carlo, WA McDonald, SA Fanaroff, AA Vohr, BR Stoll, BJ Ehrenkranz, RA Andrews, WW Wallace, D Das, A Bell, EF Walsh, MC Laptook, AR Shankaran, S Poindexter, BB Hale, EC Newman, NS Davis, AS Schibler, K Kennedy, KA Sanchez, PJ Van Meurs, KP Goldberg, RN Watterberg, KL Faix, RG Frantz, ID Higgins, RD AF Carlo, Waldemar A. McDonald, Scott A. Fanaroff, Avroy A. Vohr, Betty R. Stoll, Barbara J. Ehrenkranz, Richard A. Andrews, William W. Wallace, Dennis Das, Abhik Bell, Edward F. Walsh, Michele C. Laptook, Abbot R. Shankaran, Seetha Poindexter, Brenda B. Hale, Ellen C. Newman, Nancy S. Davis, Alexis S. Schibler, Kurt Kennedy, Kathleen A. Sanchez, Pablo J. Van Meurs, Krisa P. Goldberg, Ronald N. Watterberg, Kristi L. Faix, Roger G. Frantz, Ivan D., III Higgins, Rosemary D. CA Eunice Kennedy Shriver Natl Inst TI Association of Antenatal Corticosteroids With Mortality and Neurodevelopmental Outcomes Among Infants Born at 22 to 25 Weeks' Gestation EDITORIAL COMMENT SO OBSTETRICAL & GYNECOLOGICAL SURVEY LA English DT Editorial Material AB The benefits of antenatal corticosteroids in mothers with preterm labor from 24 to 34 weeks' gestational age are well established. Because of ethical issues related to periviability and the limited availability of data on the effectiveness of antenatal corticosteroids in infants born before 24 weeks' gestation, antenatal corticosteroids are not recommended for these premature infants. However, suggestions have been made that antenatal use of these agents should be considered before 24 weeks because such infants are at high risk of severe neurodevelopmental impairment, and many are receiving intensive care. This cohort study investigated whether the use of antenatal corticosteroids in mothers of infants born at 22 and 23 weeks of gestation was associated with improvement in major outcomes. Data were obtained prospectively from 10,541 infants with a birth weight between 401 and 1000 g (n = 10,541) born at 22 to 25 weeks' gestation between 1993 and 2009, at 23 academic perinatal centers. A total of 4924 (86.5%) of these infants who survived to 18 to 22 months had follow-up examinations performed by certified examiners unaware of exposure to antenatal corticosteroids. Logistic regression analysis was used to assess the relationship between antenatal exposure to corticosteroids or no exposure and outcomes, adjusting for maternal and neonatal confounding variables. The main study outcome measure was death or neurodevelopmental impairment at an 18- to 22-month follow-up. Death or neurodevelopmental impairment occurred significantly less frequently among infants who had been exposed to antenatal corticosteroids and were born at 23 weeks' gestation (exposure: 83.4% vs. no exposure: 90.5%; adjusted odds ratio [aOR], 0.58 [95% confidence interval{CI}, 0.42-0.80]), at 24 weeks' gestation (exposure: 68.4% vs. no exposure: 80.3%; aOR, 0.62 [95% CI, 0.49-0.78]), and at 25 weeks' gestation (exposure: 52.7% vs. no exposure: 67.9%; aOR, 0.61 [95% CI, 0.50-0.74]). There was no difference in outcomes for infants born at 22 weeks' gestation (90.2% with exposure vs. 93.1% without exposure; aOR, 0.80 [95% CI, 0.29-2.21]). Events occurring significantly less among infants who were born at 23, 24, and 25 weeks' gestation and exposed to antenatal corticosteroids were the following: death by 18 to 22 months, hospital death, the composite of death, intraventricular hemorrhage or periventricular leukomalacia, and the composite of death or necrotizing enterocolitis. The only outcome that occurred significantly less among infants born at 22 weeks' gestation was the composite of death or necrotizing enterocolitis (exposure: 73.5% vs. no exposure: 84.5%; the aOR was 0.54, with a 95% CI of 0.30 to 0.97. These findings show that antenatal exposure of infants born at 23 to 25 weeks' gestation to corticosteroids was associated with a lower rate of death or neurodevelopmental impairment at 18 to 22 months compared with nonexposure. C1 [Carlo, Waldemar A.] Univ Alabama, Dept Pediat, Birmingham, AL USA. Childrens Hosp Alabama, Birmingham, AL USA. RTI Int, Stat & Epidemiol Unit, Res Triangle Pk, NC USA. Case Western Reserve Univ, Rainbow Babies & Childrens Hosp, Dept Pediat, Cleveland, OH 44106 USA. Brown Univ, Women & Infants Hosp, Dept Pediat, Providence, RI 02908 USA. Emory Univ, Sch Med, Dept Pediat, Atlanta, GA USA. Childrens Hlth Care Atlanta, Atlanta, GA USA. Yale Univ, Sch Med, Dept Pediat, New Haven, CT 06510 USA. RTI Int, Stat & Epidemiol Unit, Rockville, MD USA. Univ Iowa, Dept Pediat, Iowa City, IA 52242 USA. Wayne State Univ, Dept Pediat, Detroit, MI 48202 USA. Indiana Univ Sch Med, Dept Pediat, Indianapolis, IN USA. Stanford Univ, Sch Med, Dept Pediat, Div Neonatal & Dev Med, Palo Alto, CA 94304 USA. Lucile Packard Childrens Hosp, Palo Alto, CA USA. Univ Cincinnati, Dept Pediat, Cincinnati, OH 45221 USA. Univ Texas Med Sch, Dept Pediat, Houston, TX USA. Univ Texas SW Med Ctr Dallas, Dept Pediat, Dallas, TX 75390 USA. Duke Univ, Dept Pediat, Durham, NC 27706 USA. Univ New Mexico, Dept Pediat, Hlth Sci Ctr, Albuquerque, NM 87131 USA. Univ Utah, Sch Med, Dept Pediat, Div Neonatol, Salt Lake City, UT USA. Floating Hosp Children, Tufts Med Ctr, Dept Pediat, Div Newborn Med, Boston, MA USA. Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Bethesda, MD USA. RP Carlo, WA (reprint author), Univ Alabama, Dept Pediat, Birmingham, AL USA. NR 2 TC 0 Z9 0 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0029-7828 J9 OBSTET GYNECOL SURV JI Obstet. Gynecol. Surv. PD APR PY 2012 VL 67 IS 4 BP 215 EP 217 DI 10.1097/OGX.0b013e31825021ef PG 3 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 925WO UT WOS:000302793000005 ER PT J AU Bukowski, R Carpenter, M Conway, D Coustan, D Dudley, DJ Goldenberg, RL Hogue, CJR Koch, MA Parker, CB Pinar, H Reddy, UM Saade, GR Silver, RM Stoll, BJ Varner, MW Willinger, M AF Bukowski, Radek Carpenter, Marshall Conway, Deborah Coustan, Donald Dudley, Donald J. Goldenberg, Robert L. Hogue, Carol J. Rowland Koch, Matthew A. Parker, Corette B. Pinar, Halit Reddy, Uma M. Saade, George R. Silver, Robert M. Stoll, Barbara J. Varner, Michael W. Willinger, Marian CA Stillbirth Collaborative Res TI Causes of Death Among Stillbirths EDITORIAL COMMENT SO OBSTETRICAL & GYNECOLOGICAL SURVEY LA English DT Editorial Material AB The stillbirth rate in the United States is higher than that of other developed countries. Since 2003, the rate has stagnated at 6.2 stillbirths per 1000 births. There is a lack of information on causes of stillbirth. Strategies to reduce the stillbirth rate will require systematic investigation into the cause of death. The stillbirth rate among non-Hispanic black women is 2.3-fold higher than that of non-Hispanic white women. This racial disparity is largely unexplained. This multicenter population-based case-control study determined the causes of death among stillbirths and stratified the causes according to race/ethnicity. All stillbirths that occurred at 20 weeks or later between 2006 and 2008 were examined in data from 59 tertiary care and community hospitals that had access to at least 90% of the stillbirth and live birth deliveries in 5 catchment areas defined by state and county boundaries. Data on deliveries resulting from termination of a live fetus were excluded. Several outcome measures were evaluated to systematically assign causes of death. Standardized perinatal postmortem examination and placental pathology evaluation were performed at delivery. Other outcome measures included medical history, karyotype, and other laboratory tests. Of the 663 women with stillbirth enrolled, 500 (75.4%) allowed a complete postmortem examination of their 512 stillborn neonates. Among the stillbirths, a probable cause of death was found for 312 cases (60.9%; 95% confidence interval [CI], 56.5%-65.2%) and possible or probable cause for 390 (76.2%; 95% CI, 72.2%-79.8%). The most common causes of death were the following: obstetric complications (29.3%; 95% CI, 25.4%-33.5%), placental abnormalities (23.6%; 95% CI, 20.1%-27.6%), fetal genetic/structural abnormalities (13.7%; 95% CI, 10.9%-17.0%), infection (12.9%; 95% CI, 10.2%-16.2%), umbilical cord abnormalities (10.4%; 95% CI, 7.9%-13.4%), hypertensive disorders (9.2%; 95% CI, 6.9%-12.1%), and other maternal medical complications (7.8%; 95% CI, 5.7%-10.6%). Compared with non-Hispanic white women and all Hispanics, non-Hispanic black women had a higher proportion of stillbirths associated with obstetric complications (43.5% vs. 23.7%; difference: 19.8%; 95% CI, 9.7%-29.9%; P < 0.001) and infections (25.2% vs. 7.8%; difference: 17.4%; 95% CI, 9.0%-25.8%; P < 0.001). Intrapartum and early in gestation stillbirths were more common among non-Hispanic black women. The most likely sources contributing to identifying a probable or possible cause of death were placental histology (52.3%; 95% CI, 47.9%-56.7%), perinatal postmortem examination (31.4%; 95% CI, 27.5%-35.7%), and karyotype (9%; 95% CI, 6.3%-12.5%). These findings show that a systematic and thorough evaluation of a population-based cohort led to a probable or possible cause of death for the majority of cases of stillbirth. Causes were differentially distributed by race/ethnicity. C1 [Bukowski, Radek] Univ Texas Med Branch, Dept Obstet & Gynecol, Galveston, TX 77555 USA. Brown Univ, Sch Med, Div Maternal Fetal Med, Dept Obstet & Gynecol, Providence, RI 02912 USA. Univ Texas Hlth Sci Ctr San Antonio, Dept Obstet & Gynecol, Div Maternal Fetal Med, San Antonio, TX 78229 USA. Drexel Univ, Sch Med, Dept Obstet & Gynecol, Philadelphia, PA 19104 USA. Emory Univ, Rollins Sch Publ Hlth, Dept Epidemiol, Atlanta, GA 30322 USA. Emory Univ, Womens & Childrens Ctr, Atlanta, GA 30322 USA. RTI Int, Stat & Epidemiol Unit, Div Hlth Sci, Res Triangle Pk, NC USA. Brown Univ, Sch Med, Dept Pathol & Lab Med, Div Perinatal & Pediat Pathol, Providence, RI 02912 USA. Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Pregnancy & Perinatol Branch, NIH, Bethesda, MD USA. Univ Utah, Sch Med, Dept Obstet & Gynecol, Div Maternal Fetal Med, Salt Lake City, UT 84132 USA. Intermt Healthcare, Maternal Fetal Med, Salt Lake City, UT USA. Emory Univ, Sch Med, Atlanta, GA 30322 USA. Childrens Healthcare Atlanta, Dept Pediat, Atlanta, GA USA. RP Bukowski, R (reprint author), Univ Texas Med Branch, Dept Obstet & Gynecol, Galveston, TX 77555 USA. RI Hogue, Carol/H-5442-2012 NR 5 TC 0 Z9 0 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0029-7828 J9 OBSTET GYNECOL SURV JI Obstet. Gynecol. Surv. PD APR PY 2012 VL 67 IS 4 BP 223 EP 225 DI 10.1097/OGX.0b013e3182502211 PG 3 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 925WO UT WOS:000302793000009 ER PT J AU Lu, C Zhu, X Willingham, MC Cheng, SY AF Lu, C. Zhu, X. Willingham, M. C. Cheng, S-Y TI Activation of tumor cell proliferation by thyroid hormone in a mouse model of follicular thyroid carcinoma SO ONCOGENE LA English DT Article DE thyroid hormone; follicular thyroid carcinoma; animal model; protein kinase B/AKT; PTEN ID BETA-CATENIN; PHOSPHATIDYLINOSITOL 3-KINASE; GENETIC ALTERATIONS; RECEPTOR-BETA; TRANSCRIPTIONAL ACTIVITY; METASTATIC SPREAD; TRANSFORMING GENE; PROTEIN-KINASE; GROWTH-FACTOR; CANCER AB Thyroid cancers are the most common malignancy of the endocrine system in humans. To understand the molecular genetic events underlying thyroid carcinogenesis, we have generated a mouse model that spontaneously develops follicular thyroid carcinoma similar to human thyroid cancer (Thrb(PV/PV) mouse). This mutant mouse harbors a dominant-negative mutated thyroid hormone receptor beta (denoted PV). The PV mutation was identified in a patient with resistance to thyroid hormone (TH). Thrb(PV/PV) mice exhibit highly elevated serum thyroid-stimulating hormone levels and increased TH. We have previously shown that thyroid-stimulating hormone is required, but not sufficient to induce metastatic follicular thyroid cancer in Thrb(PV/PV) mice. However, whether the elevated TH also contributes to the thyroid carcinogenesis of Thrb(PV/PV) mice was not elucidated. To understand the role of TH in thyroid carcinogenesis, we blocked the production of TH by treating Thrb(PV/PV) mice with propylthiouracil (Thrb(PV/PV)-PTU mice) and compared the development of thyroid cancer in Thrb(PV/PV)-PTU and untreated ThrbPV/PV mice. We found that thyroid tumor growth was reduced by similar to 42% in Thrb(PV/PV)-PTU mice as compared with Thrb(PV/PV) mice. Analysis by bromodeoxyuridine-nuclear labeling showed decreased incorporation of bromodeoxyuridine in thyroid tumor cells of Thrb(PV/PV)-PTU mice, indicative of decreased tumor cell proliferation. However, cleaved-caspase 3 staining showed no apparent changes in apoptosis of tumor cells in Thrb(PV/PV)-PTU mice. Molecular studies identified a marked attenuation of the PI3K-AKT-beta-catenin signaling pathway that led to decreased protein levels of cyclin D2, thereby decreasing tumor cell proliferation in Thrb(PV/PV)-PTU mice. Furthermore, matrix metalloproteinase-2, a downstream target of beta-catenin and a key regulator during tumor invasion and metastasis, was also decreased. Thus, the present study uncovers a critical role of TH in promoting the thyroid carcinogenesis of Thrb(PV/PV) mice via membrane signaling events. Importantly, these findings suggest that anti-thyroid drugs could be considered as possible therapeutic agents of thyroid cancer. Oncogene (2012) 31, 2007-2016; doi: 10.1038/onc.2011.390; published online 12 September 2011 C1 [Lu, C.; Zhu, X.; Cheng, S-Y] NCI, Mol Biol Lab, Ctr Canc Res, Bethesda, MD 20892 USA. [Willingham, M. C.] Wake Forest Univ, Dept Pathol, Winston Salem, NC 27109 USA. RP Cheng, SY (reprint author), NCI, Mol Biol Lab, Ctr Canc Res, 37 Convent Dr,Room 5128, Bethesda, MD 20892 USA. EM chengs@mail.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 National Institutes of Health, National Cancer Institute, Center for Cancer Research. NR 50 TC 6 Z9 7 U1 2 U2 4 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0950-9232 J9 ONCOGENE JI Oncogene PD APR PY 2012 VL 31 IS 16 BP 2007 EP 2016 DI 10.1038/onc.2011.390 PG 10 WC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity GA 928TP UT WOS:000303008600002 PM 21909131 ER PT J AU Chu, IM Michalowski, AM Hoenerhoff, M Szauter, KM Luger, D Sato, M Flanders, K Oshima, A Csiszar, K Green, JE AF Chu, I. M. Michalowski, A. M. Hoenerhoff, M. Szauter, K. M. Luger, D. Sato, M. Flanders, K. Oshima, A. Csiszar, K. Green, J. E. TI GATA3 inhibits lysyl oxidase-mediated metastases of human basal triple-negative breast cancer cells SO ONCOGENE LA English DT Article DE GATA3; basal triple-negative breast cancer; lysyl oxidase; differentiation; gene expression profiling ID GENE-EXPRESSION; MESENCHYMAL TRANSITION; ENZYME-ACTIVITY; MAMMARY-GLAND; DIFFERENTIATION; GROWTH; MORPHOGENESIS; PROPEPTIDE; MIGRATION; SUBTYPES AB Discovery of mechanisms that impede the aggressive and metastatic phenotype of human basal triple-negative-type breast cancers (BTNBCs) could provide novel targets for therapy for this form of breast cancer that has a relatively poor prognosis. Previous studies have demonstrated that expression of GATA3, the master transcriptional regulator of mammary luminal differentiation, can reduce the tumorigenicity and metastatic propensity of the human BTNBC MDA-MB-231 cell line (MB231), although the mechanism for reduced metastases was not elucidated. We demonstrate through gene expression profiling that GATA3 expression in 231 cells resulted in the dramatic reduction in the expression of lysyl oxidase (LOX), a metastasis-promoting, matrix-remodeling protein, in part, through methylation of the LOX promoter. Suppression of LOX expression by GATA3 was further confirmed in the BTNBC Hs578T cell line. Conversely, reduction of GATA3 expression by small interfering RNA in luminal BT474 cells increased LOX expression. Reconstitution of LOX expression in 231-GATA3 cells restored metastatic propensity. A strong inverse association between LOX and GATA3 expression was confirmed in a panel of 51 human breast cancer cell lines. Similarly, human breast cancer microarray data demonstrated that high LOX/low GATA3 expression is associated with the BTNBC subtype of breast cancer and poor patient prognosis. Expression of GATA3 reprograms BTNBCs to a less aggressive phenotype and inhibits a major mechanism of metastasis through inhibition of LOX. Induction of GATA3 in BTNBC cells or novel approaches that inhibit LOX expression or activity could be important strategies for treating BTNBCs. Oncogene (2012) 31, 2017-2027; doi: 10.1038/onc.2011.382; published online 5 September 2011 C1 [Green, J. E.] NCI, Transgen Oncogenesis & Genom Sect, Lab Canc Biol & Genet, Bethesda, MD 20892 USA. [Hoenerhoff, M.] NIEHS, Cellular & Mol Pathol Branch, Natl Toxicol Program, Res Triangle Pk, NC 27709 USA. [Szauter, K. M.; Csiszar, K.] Univ Hawaii, John A Burns Sch Med, Honolulu, HI 96822 USA. RP Green, JE (reprint author), NCI, Transgen Oncogenesis & Genom Sect, Lab Canc Biol & Genet, Bldg 37,Room 4054,37 Convent Dr, Bethesda, MD 20892 USA. EM jegreen@nih.gov FU Center for Cancer Research, NCI, NIH; Department of Defense [W81XWH-10-2-0030] FX We thank Drs Lalage Wakefield and Li Yang for helpful scientific discussions. We also thank Lara El-Touny, Dalit Barkan, Zi-Yao Liu, TingHu Qiu, Anthony Vieira, Christina Bennett, Christine Tomlinson, Steven Austin, Christian Mustroph and Wei-Chu Lai for technical assistance; Paul Meltzer for sharing unpublished data; the LRBGE Fluorescence Imaging Core and Chand Khanna for the use of fluorescence microscopy equipment; and Julie Foley and Norris Flagler for technical assistance with image analysis. This research was supported in part by the Intramural Research Program, Center for Cancer Research, NCI, NIH. IMC acknowledges support from the Department of Defense Breast Cancer Research Program (W81XWH-10-2-0030). NR 34 TC 15 Z9 15 U1 3 U2 7 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0950-9232 J9 ONCOGENE JI Oncogene PD APR PY 2012 VL 31 IS 16 BP 2017 EP 2027 DI 10.1038/onc.2011.382 PG 11 WC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity GA 928TP UT WOS:000303008600003 PM 21892208 ER PT J AU Zhang, YH Qi, YW Li, J Liu, SF Hong, LX Lin, TL Long, C Su, XZ AF Zhang, Yanhui Qi, Yanwei Li, Jian Liu, Shengfa Hong, Lingxian Lin, Tianlong Long, Carole Su, Xin-zhuan TI A new malaria antigen produces partial protection against Plasmodium yoelii challenge SO PARASITOLOGY RESEARCH LA English DT Article ID IMMUNE ADULT MEN; FALCIPARUM MALARIA; VACCINE; PARASITE; INFECTION; SELECTION; EFFICACY; GAMBIA; GENE AB Of all the parasitic diseases, malaria is the number one killer. Despite tremendous efforts in disease control and research, nearly a million people, primarily children, still die from the disease each year, partly due to drug resistance and the lack of an effective vaccine. Many parasite antigens have been identified and evaluated for vaccine development; however, none has been approved for human use. Antigenic variation, complex life cycle, and inadequate understanding of the mechanisms of parasite-host interaction and of host immune response all contribute to the lack of an effective vaccine for malaria control. In a recent search of genome-wide polymorphism in Plasmodium falciparum, several molecules were found to be recognized by sera from patients infected with the P. falciparum parasite. Here, we have expressed a 350-amino acid N terminus from one of the homologous candidate antigen genes from the rodent malaria parasite Plasmodium yoelii (Py01157, a putative dentin phosphorin) in bacteria and evaluated the immune response and protection generated after immunization with the recombinant protein. We showed that the recombinant protein was recognized by sera from both mice and humans infected with malaria parasites. Partial protection was observed after challenge with non-lethal P. yoelii 17XNL but not with the lethal P. yoelii 17XL parasite. Further tests using a full-length protein or the conserved C terminus may provide additional information on whether this protein has the potential for being a malaria vaccine. C1 [Zhang, Yanhui; Long, Carole; Su, Xin-zhuan] NIAID, Lab Malaria & Vector Res, NIH, Bethesda, MD 20892 USA. [Zhang, Yanhui; Qi, Yanwei; Li, Jian; Liu, Shengfa; Hong, Lingxian] Xiamen Univ, State Key Lab Stress Cell Biol, Xiamen 361005, Fujian, Peoples R China. [Lin, Tianlong] Fujian Acad Agr Sci, Fuzhou 350003, Fujian, Peoples R China. RP Su, XZ (reprint author), NIAID, Lab Malaria & Vector Res, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA. EM xsu@niaid.nih.gov OI Su, Xinzhuan/0000-0003-3246-3248 FU 973 Program of China [2007CB513103]; Science Planning Program of Fujian Province [2010J1008]; 111 Project of Education of China [B06016]; Division of Intramural Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health FX This work is supported by grants from the 973 Program 2007CB513103 of China, the Science Planning Program of Fujian Province (2010J1008), 111 Project of Education of China (no. B06016), and by the Intramural Research Program of the Division of Intramural Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health. We thank NIAID intramural editor Brenda Rae Marshall for assistance. NR 23 TC 2 Z9 2 U1 0 U2 2 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0932-0113 J9 PARASITOL RES JI Parasitol. Res. PD APR PY 2012 VL 110 IS 4 BP 1337 EP 1345 DI 10.1007/s00436-011-2630-y PG 9 WC Parasitology SC Parasitology GA 926EQ UT WOS:000302814500004 PM 21915626 ER PT J AU Simmons, WK Martin, A AF Simmons, W. Kyle Martin, Alex TI Spontaneous resting-state BOLD fluctuations reveal persistent domain-specific neural networks SO SOCIAL COGNITIVE AND AFFECTIVE NEUROSCIENCE LA English DT Article DE social cognition; tools; resting-state functional connectivity; posterior superior temporal sulcus; middle temporal gyrus ID ANTERIOR TEMPORAL-LOBES; FUSIFORM FACE AREA; FUNCTIONAL CONNECTIVITY; MANIPULATABLE OBJECTS; SOCIAL COGNITION; DEFAULT MODE; BIOLOGICAL MOTION; SEMANTIC MEMORY; BRAIN ACTIVITY; CORTEX AB Resting-state functional connectivity MRI (rs-fcMRI) analyses have identified intrinsic neural networks supporting domain-general cognitive functions including language, attention, executive control and memory. The brain, however, also has a domain-specific organization, including regions that contribute to perceiving and knowing about others (the 'social' system) or manipulable objects designed to perform specific functions (the 'tool' system). These 'social' and 'tool' systems, however, might not constitute intrinsic neural networks per se, but rather only come online as needed to support retrieval of domain-specific information during social- or tool-related cognitive tasks. To address this issue, we functionally localized two regions in lateral temporal cortex activated when subjects perform social- and tool conceptual tasks. We then compared the strength of the correlations with these seed regions during rs-fcMRI. Here, we show that the 'social' and 'tool' neural networks are maintained even when subjects are not engaged in social- and tool-related information processing, and so constitute intrinsic domain-specific neural networks. C1 [Simmons, W. Kyle] Laureate Inst Brain Res, Tulsa, OK 74136 USA. [Simmons, W. Kyle; Martin, Alex] NIMH, Lab Brain & Cognit, Bethesda, MD 20892 USA. RP Simmons, WK (reprint author), Laureate Inst Brain Res, 6655 S Yale Ave, Tulsa, OK 74136 USA. EM wksimmons@laureateinstitute.org RI martin, alex/B-6176-2009; Simmons, William/K-8925-2015 OI Simmons, William/0000-0002-0399-9003 FU National Institute of Mental Health Division of Intramural Research, National Institutes of Health FX This work was supported by the National Institute of Mental Health Division of Intramural Research, National Institutes of Health. NR 56 TC 26 Z9 26 U1 0 U2 9 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 1749-5016 J9 SOC COGN AFFECT NEUR JI Soc. Cogn. Affect. Neurosci. PD APR PY 2012 VL 7 IS 4 BP 467 EP 475 DI 10.1093/scan/nsr018 PG 9 WC Neurosciences; Psychology; Psychology, Experimental SC Neurosciences & Neurology; Psychology GA 926CF UT WOS:000302808200011 PM 21586527 ER PT J AU Danis, M Pesce, J AF Danis, Marion Pesce, Julianna TI Prospects for acknowledging and addressing the socioeconomic determinants of health in the United States: A response to Goldberg SO SOCIAL SCIENCE & MEDICINE LA English DT Editorial Material DE Health status disparities; Factors, socioeconomic; USA; Health policy, national; Public opinion; Expert opinions ID POLICY C1 [Danis, Marion] NIH, Dept Clin Bioeth, Bethesda, MD 20892 USA. [Pesce, Julianna] Univ Calif Los Angeles, Sch Med, Los Angeles, CA 90024 USA. RP Danis, M (reprint author), NIH, Dept Clin Bioeth, Bldg 10,Room 1C118,10 Ctr Dr MSC 1156, Bethesda, MD 20892 USA. EM mdanis@nih.gov; juliannapesce@ucla.edu NR 14 TC 0 Z9 0 U1 0 U2 3 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0277-9536 J9 SOC SCI MED JI Soc. Sci. Med. PD APR PY 2012 VL 74 IS 8 BP 1143 EP 1145 DI 10.1016/j.socscimed.2011.11.041 PG 3 WC Public, Environmental & Occupational Health; Social Sciences, Biomedical SC Public, Environmental & Occupational Health; Biomedical Social Sciences GA 928JE UT WOS:000302978200002 ER PT J AU Shindo, S Sakuma, T Negishi, M Squires, J AF Shindo, Sawako Sakuma, Tsutomu Negishi, Masahiko Squires, James TI Phosphorylation of serine 212 confers novel activity to human estrogen receptor alpha SO STEROIDS LA English DT Article DE Estrogen receptor; Phosphorylation; DNA binding domain; Gene expression; Nuclear receptor CAR ID CAR AB Estrogen receptor alpha (ER alpha) can be phosphorylated at various residues, one of which is serine 212 in the DNA binding domain. The majority of human nuclear receptors conserves, as a motif, this serine residue within their DNA binding domain. Among these nuclear receptors, phosphorylation of the corresponding threonine 38 in the nuclear receptor CAR is essential for determining its activity [9]. Here, we have investigated the role of phosphorylated serine 212 in the regulation of ER alpha activity by comparing it with serine 236, another potential phosphorylation site within the DNA binding domain, and demonstrated that phosphorylation of serine 212 confers upon ER alpha a distinct activity regulating gene expression in Huh-7 cells. In Western blot analysis, wild type ER alpha and mutants ER alpha S212A, ER alpha S212D, ER alpha S236A and ER alpha S236D were equally expressed in the nucleus, thus indicating that phosphorylation does not determine nuclear localization of ER alpha. ER alpha S212D, but not ER alpha S236D, retained its capability of activating an ERE-reporter gene in luciferase assays. Similar results were also obtained for human ER beta: the ER beta S176D mutant retained its trans-activation activity, but the ER beta S200D mutant did not. cDNA microarray and Ingenuity Pathway Analysis, employed on Huh-7 cells ectopically expressing either ER alpha S212A or ER alpha S212D, revealed that phosphorylation of serine 212 enabled ER alpha to regulate a unique set of genes and cellular functions. Published by Elsevier Inc. C1 [Shindo, Sawako; Sakuma, Tsutomu; Negishi, Masahiko; Squires, James] Natl Inst Environm Hlth Sci, Pharmacogenet Sect, Lab Reprod & Dev Toxicol, NIH, Res Triangle Pk, NC 27709 USA. RP Negishi, M (reprint author), Natl Inst Environm Hlth Sci, Pharmacogenet Sect, Lab Reprod & Dev Toxicol, NIH, Res Triangle Pk, NC 27709 USA. EM negishi@niehs.nih.gov FU National Institute of Environmental Health Sciences [Z01ES1005-01] FX We thank the laboratory of Dr. Ken Korach at NIEHS for kindly providing us with human ER alpha and ER beta plasmids as well as for useful suggestions. We also thank Dr. Kosuke Saito for ANOVA analysis and the DNA sequencing and cDNA microarray cores of NIEHS for their assistance. This research was supported by the Intramural Research Program of National Institute of Environmental Health Sciences, Z01ES1005-01. NR 12 TC 4 Z9 4 U1 0 U2 3 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0039-128X J9 STEROIDS JI Steroids PD APR PY 2012 VL 77 IS 5 BP 448 EP 453 DI 10.1016/j.steroids.2012.01.001 PG 6 WC Biochemistry & Molecular Biology; Endocrinology & Metabolism SC Biochemistry & Molecular Biology; Endocrinology & Metabolism GA 929RU UT WOS:000303084000013 PM 22266331 ER PT J AU Valeri, CR Veech, RL AF Valeri, C. Robert Veech, Richard L. TI The unrecognized effects of the volume and composition of the resuscitation fluid used during the administration of blood products SO TRANSFUSION AND APHERESIS SCIENCE LA English DT Article ID KETONE-BODIES; INSULIN; CELLS AB Background: Recent publications have reported the severe adverse events associated with blood products but have not considered the effect of the volume and composition of the resuscitative fluids infused with the blood products. Methods: Injury leads to cellular reaction characterized by insulin resistance during which glucose cannot enter muscle and fat cells. In all cells, mitochondrial pyruvate dehydrogenase activity is decreased during insulin deficiency leaving cells deficient in substrates needed to power the Krebs cycle and make ATP. Results: D-beta-Hydroxybutyrate, a normal ketone body metabolite, enters cells on the monocarboxylate transport mimicking the action of insulin and bypassing the enzymatic block at PDH. Metabolism of ketone bodies increases efficiency of mitochondrial energy production and cellular ATP level. Conclusion: Infusion of 250 ml of 600 mM Na D-beta-hydroxybutyrate solution, with the same osmotic strength as the hypertonic NaCl solution currently being used, would correct insulin resistance, provide energy substrates for cells to produce ATP, correct the tendency of injured tissue to swell due to decreased energy of ionic gradients and correct acidosis observed in hemorrhage. (C) 2012 Elsevier Ltd. All rights reserved. C1 [Valeri, C. Robert] Naval Blood Res Lab Inc, Plymouth, MA 02360 USA. [Veech, Richard L.] NIAAA, Lab Metab Control, NIH, Rockville, MD 20852 USA. RP Valeri, CR (reprint author), Naval Blood Res Lab Inc, 195 Bournehurst Dr, Plymouth, MA 02360 USA. EM navblood@nbrl.org FU Defense Research Project Administration, DARPA FX Support for development of the ketone ester from the Defense Research Project Administration, DARPA, is gratefully acknowledged. NR 22 TC 3 Z9 3 U1 0 U2 3 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 1473-0502 J9 TRANSFUS APHER SCI JI Transfus. Apher. Sci. PD APR PY 2012 VL 46 IS 2 BP 121 EP 123 DI 10.1016/j.transci.2012.01.010 PG 3 WC Hematology SC Hematology GA 926JI UT WOS:000302826800002 ER PT J AU Liu, Y Wilson, SH AF Liu, Yuan Wilson, Samuel H. TI DNA base excision repair: a mechanism of trinucleotide repeat expansion SO TRENDS IN BIOCHEMICAL SCIENCES LA English DT Review ID CELL NUCLEAR ANTIGEN; FLAP ENDONUCLEASE-1; CAG REPEAT; SACCHAROMYCES-CEREVISIAE; POLYMERASE-BETA; GENETIC INSTABILITY; SECONDARY STRUCTURE; HUNTINGTON-DISEASE; ESCHERICHIA-COLI; MOUSE MODEL AB The expansion of trinucleotide repeat (TNR) sequences in human DNA is considered to be a key factor in the pathogenesis of more than 40 neurodegenerative diseases. TNR expansion occurs during DNA replication and also, as suggested by recent studies, during the repair of DNA lesions produced by oxidative stress. In particular, the oxidized guanine base 8-oxoguanine within sequences containing CAG repeats may induce formation of pro-expansion intermediates through strand slippage during DNA base excision repair (BER). In this article, we describe how oxidized DNA lesions are repaired by BER and discuss the importance of the coordinated activities of the key repair enzymes, such as DNA polymerase beta, flap endonuclease 1 (FEN1) and DNA ligase, in preventing strand slippage and TNR expansion. C1 [Liu, Yuan] Florida Int Univ, Dept Chem & Biochem, Miami, FL 33199 USA. [Wilson, Samuel H.] NIEHS, Struct Biol Lab, NIH, Res Triangle Pk, NC 27709 USA. RP Liu, Y (reprint author), Florida Int Univ, Dept Chem & Biochem, 11200 SW 8th St, Miami, FL 33199 USA. EM yualiu@fiu.edu; wilson5@niehs.nih.gov FU NIH from the National Institute of Environmental Health Sciences (NIEHS) [Z01-ES050158, Z01-ES050159]; NIH [ES017476] FX We thank Bonnie Mesmer for editorial assistance and Dr Lawrence Loeb and students at the University of Washington for discussions. This work was supported by NIH Projects Z01-ES050158 and Z01-ES050159 from the National Institute of Environmental Health Sciences (NIEHS) Intramural Research Program and NIH grant ES017476 (to Y.L.). NR 75 TC 41 Z9 42 U1 0 U2 24 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 APR PY 2012 VL 37 IS 4 BP 162 EP 172 DI 10.1016/j.tibs.2011.12.002 PG 11 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 929TC UT WOS:000303087600005 PM 22285516 ER PT J AU Azzam, KM Fessler, MB AF Azzam, Kathleen M. Fessler, Michael B. TI Crosstalk between reverse cholesterol transport and innate immunity SO TRENDS IN ENDOCRINOLOGY AND METABOLISM LA English DT Review ID APOLIPOPROTEIN-A-I; PHOSPHOLIPID-TRANSFER PROTEIN; LIPOPOLYSACCHARIDE-BINDING PROTEIN; TOLL-LIKE RECEPTORS; NECROSIS-FACTOR-ALPHA; LIVER-X-RECEPTORS; LIPID RAFTS; INFLAMMATORY RESPONSE; SIGNALING PATHWAYS; MIMETIC PEPTIDE AB Although lipid metabolism and host defense are widely considered to be very divergent disciplines, compelling evidence suggests that host cell handling of self- and microbe-derived (e.g. lipopolysaccharide, LPS) lipids may have common evolutionary roots, and that they indeed may be inseparable processes. The innate immune response and the homeostatic network controlling cellular sterol levels are now known to regulate each other reciprocally, with important implications for several common diseases, including atherosclerosis. In the present review we discuss recent discoveries that provide new insight into the bidirectional crosstalk between reverse cholesterol transport and innate immunity, and highlight the broader implications of these findings for the development of therapeutics. C1 [Azzam, Kathleen M.; Fessler, Michael B.] NIEHS, Lab Resp Biol, NIH, Res Triangle Pk, NC 27709 USA. RP Fessler, MB (reprint author), NIEHS, Lab Resp Biol, NIH, POB 12233, Res Triangle Pk, NC 27709 USA. EM fesslerm@niehs.nih.gov FU National Institutes of Health, National Institute of Environmental Health Sciences [Z01 ES102005] FX The authors thank Sue Edelstein for figure design. This work was supported in part by the Intramural Research Program of the National Institutes of Health, National Institute of Environmental Health Sciences (Z01 ES102005). NR 100 TC 25 Z9 25 U1 0 U2 8 PU ELSEVIER SCIENCE LONDON PI LONDON PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND SN 1043-2760 J9 TRENDS ENDOCRIN MET JI Trends Endocrinol. Metab. PD APR PY 2012 VL 23 IS 4 BP 169 EP 178 DI 10.1016/j.tem.2012.02.001 PG 10 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 927EW UT WOS:000302890900003 PM 22406271 ER PT J AU Sorlie, PD Bild, DE Lauer, MS AF Sorlie, Paul D. Bild, Diane E. Lauer, Michael S. TI Cardiovascular Epidemiology in a Changing World-Challenges to Investigators and the National Heart, Lung, and Blood Institute SO AMERICAN JOURNAL OF EPIDEMIOLOGY LA English DT Editorial Material DE cardiovascular diseases; epidemiology; National Institutes of Health (US); research ID ACUTE MYOCARDIAL-INFARCTION; ELECTRONIC HEALTH RECORDS; RISK PREDICTION; UNITED-STATES; POPULATION; IMPROVEMENTS; PREVENTION; WORKSHOP; GENOMICS; PROTEIN AB Over the past 60 years, revolutionary discoveries made by epidemiologists have contributed to marked declines in cardiovascular disease morbidity and mortality. Now, in an era of increasingly constrained resources, researchers in cardiovascular epidemiology face a number of challenges that call for novel, paradigm-shifting approaches. In this paper, the authors pose to the community 4 critical questions: 1) How can we avoid wasting resources on studies that provide little incremental knowledge? 2) How can we assure that we direct our resources as economically as possible towards innovative science? 3) How can we be nimble, responding quickly to new opportunities? 4) How can we identify prospectively the most meritorious research questions? Senior program staff at the National Heart, Lung, and Blood Institute invite the epidemiology community to join them in an ongoing Web-based blog conversation so that together we might develop novel approaches that will facilitate the next generation of high-impact discoveries. C1 [Sorlie, Paul D.; Lauer, Michael S.] NHLBI, Div Cardiovasc Sci, Epidemiol Branch, Bethesda, MD 20892 USA. [Bild, Diane E.] NHLBI, Program Prevent & Populat Sci, Div Cardiovasc Sci, Bethesda, MD 20892 USA. RP Lauer, MS (reprint author), NHLBI, Div Cardiovasc Sci, Epidemiol Branch, 6701 Rockledge Dr,Room 8128, Bethesda, MD 20892 USA. EM lauerm@nhlbi.nih.gov RI Lauer, Michael/L-9656-2013 OI Lauer, Michael/0000-0002-9217-8177 NR 33 TC 16 Z9 16 U1 0 U2 6 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 APR 1 PY 2012 VL 175 IS 7 BP 597 EP 601 DI 10.1093/aje/kws138 PG 5 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 921NE UT WOS:000302483500001 PM 22415032 ER PT J AU Weinberg, CR AF Weinberg, Clarice R. TI Interaction and Exposure Modification: Are We Asking the Right Questions? SO AMERICAN JOURNAL OF EPIDEMIOLOGY LA English DT Editorial Material DE attributable risk; effect modification; interaction; synergy ID GENE VARIANTS; RISK; CANCER AB Most diseases arise not purely through genetic abnormalities nor purely through environmental causes, but as "complex" conditions brought about by the combined effects of genetic susceptibility factors, nongenetic experiences and exposures, and bad luck. Finding simple models capable of both characterizing such joint effects and providing new insight into pathogenesis remains an ongoing challenge in etiologic epidemiology. Additive null models can capture certain pure forms of independent etiologic effects in studies of rare conditions and can be useful for predicting possible effects of interventions. The concept of exposure modification is here proposed as useful, particularly in thinking about biologic interactions between exposures and genetic variants. Openness to parsimonious joint models and the insights they can provide is key to advancing our understanding of etiology. C1 NIEHS, Res Triangle Pk, NC 27709 USA. RP Weinberg, CR (reprint author), NIEHS, POB 12233, Res Triangle Pk, NC 27709 USA. EM weinber2@niehs.nih.gov FU Intramural NIH HHS; NIEHS NIH HHS [ZO1 ES040007., Z01 ES040007] NR 13 TC 9 Z9 9 U1 2 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 APR 1 PY 2012 VL 175 IS 7 BP 602 EP 605 DI 10.1093/aje/kwr495 PG 4 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 921NE UT WOS:000302483500002 PM 22306562 ER PT J AU Pollack, AZ Schisterman, EF Goldman, LR Mumford, SL Perkins, NJ Bloom, MS Rudra, CB Browne, RW Wactawski-Wende, J AF Pollack, Anna Z. Schisterman, Enrique F. Goldman, Lynn R. Mumford, Sunni L. Perkins, Neil J. Bloom, Michael S. Rudra, Carole B. Browne, Richard W. Wactawski-Wende, Jean TI Relation of Blood Cadmium, Lead, and Mercury Levels to Biomarkers of Lipid Peroxidation in Premenopausal Women SO AMERICAN JOURNAL OF EPIDEMIOLOGY LA English DT Article DE cadmium; hydroxyl-octadecadienoic acid; isoprostane; lead; mercury; oxidative stress; thiobarbituric acid reactive substances; women ID OXIDATIVE STRESS; MENSTRUAL-CYCLE; FATTY-ACIDS; REPRODUCTIVE HORMONES; BIOLOGICAL VARIATION; NATIONAL-HEALTH; OXIDANT STRESS; UNITED-STATES; F-2-ISOPROSTANES; PRODUCTS AB Exposures to cadmium, lead, and mercury are associated with adverse health effects, including cardiovascular disease, which may be promoted by lipid peroxidation. The authors examined cadmium, lead, and mercury in relation to plasma levels of F-2-8 alpha isoprostanes (isoprostane), 9-hydroperoxy-10,12-octadecadienoic acid (9-HODE), 13-hydroxy-9,11-octadecadienoic acid (13-HODE), and thiobarbituric acid reactive substances (TBARS) in 252 women from western New York State (2005-2007). Healthy premenopausal women were followed for <2 menstrual cycles, with biomarkers of lipid peroxidation being assessed <= 8 times per cycle. Metals were measured at baseline in whole blood. Linear mixed models were used to estimate the association between cadmium, lead, and mercury and lipid peroxidation biomarkers. Median cadmium, lead, and mercury levels were 0.30 mu g/L, 0.86 mu g/dL, and 1.10 mu g/L, respectively. Blood cadmium, lead, and mercury were not associated with increases in isoprostane, TBARS, 9-HODE, or 13-HODE levels. Isoprostane levels decreased 6.80% (95% confidence interval: -10.40, -3.20) per 1% increase in mercury. However, after adjustment for a simulated strong confounding factor, such as precisely measured fish consumption, the observed association was attenuated, suggesting that this unexpected association could be attributable to unmeasured confounding. In this population of healthy premenopausal women with low exposure levels, cadmium, lead, and mercury were not associated with elevated lipid peroxidation biomarkers. C1 [Pollack, Anna Z.; Schisterman, Enrique F.; Mumford, Sunni L.; Perkins, Neil J.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Epidemiol Branch, Div Epidemiol Stat & Prevent Res, Rockville, MD 20852 USA. [Pollack, Anna Z.; Goldman, Lynn R.] Johns Hopkins Univ Hosp, Dept Epidemiol, Bloomberg Sch Publ Hlth, Baltimore, MD 21287 USA. [Bloom, Michael S.] SUNY Albany, Sch Publ Hlth, Dept Environm Hlth Sci, Rensselaer, NY USA. [Rudra, Carole B.; Browne, Richard W.; Wactawski-Wende, Jean] SUNY Buffalo, Dept Social & Prevent Med, Buffalo, NY 14260 USA. RP Schisterman, EF (reprint author), Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Epidemiol Branch, Div Epidemiol Stat & Prevent Res, 6100 Execut Blvd,Room 7B03, Rockville, MD 20852 USA. EM schistee@mail.nih.gov RI Goldman, Lynn/D-5372-2012; OI Perkins, Neil/0000-0002-6802-4733; Pollack, Anna/0000-0002-4313-3298; Schisterman, Enrique/0000-0003-3757-641X FU Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health; Long-Range Research Initiative of the American Chemistry Council FX This research was supported by the Intramural Research Program of the Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, and by the Long-Range Research Initiative of the American Chemistry Council. NR 52 TC 7 Z9 7 U1 0 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 APR 1 PY 2012 VL 175 IS 7 BP 645 EP 652 DI 10.1093/aje/kwr375 PG 8 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 921NE UT WOS:000302483500009 PM 22302120 ER PT J AU Denadai, R Raposo-Amaral, CE Bertola, D Kim, C Alonso, N Hart, T Han, S Stelini, RF Buzzo, CL Raposo-Amaral, CA Hart, PS AF Denadai, Rafael Raposo-Amaral, Cassio E. Bertola, Debora Kim, Chong Alonso, Nivaldo Hart, Thomas Han, Sangwoo Stelini, Rafael F. Buzzo, Celso L. Raposo-Amaral, Cesar A. Hart, P. Suzanne TI Identification of 2 Novel ANTXR2 Mutations in Patients With Hyaline Fibromatosis Syndrome and Proposal of a Modified Grading System SO AMERICAN JOURNAL OF MEDICAL GENETICS PART A LA English DT Article DE anthrax toxin receptor 2 protein; capillary morphogenesis protein-2; hyaline fibromatosis syndrome; infantile systemic hyalinosis; juvenile hyaline fibromatosis ID OF-THE-LITERATURE; CAPILLARY MORPHOGENESIS PROTEIN-2; FOLLOW-UP; JUVENILE; GENE; INFANT AB Juvenile hyaline fibromatosis (JHF) and infantile systemic hyalinosis (ISH) are rare, autosomal recessive disorders of the connective tissue caused by mutations in the gene encoding the anthrax toxin receptor 2 protein (ANTXR2) located on chromosome 4q21. Characteristically, these conditions present with overlapping clinical features, such as nodules and/or pearly papules, gingival hyperplasia, flexion contractures of the joints, and osteolytic bone defects. The present report describes a pair of sibs and three other JHF/ISH patients whose diagnoses were based on typical clinical manifestations and confirmed by histopathologic analyses and/or molecular analysis. A comparison of ISH and JHF, additional thoughts about new terminology (hyaline fibromatosis syndrome) and a modified grading system are also included. (C) 2012 Wiley Periodicals, Inc. C1 [Raposo-Amaral, Cassio E.; Buzzo, Celso L.; Raposo-Amaral, Cesar A.] Brazilian Soc Res & Assistance Craniofacial Rehab, Inst Plast & Craniofacial Surg, BR-13094776 Campinas, SP, Brazil. [Denadai, Rafael] Marilia Univ, Sch Med Sci, Marilia, SP, Brazil. [Bertola, Debora; Kim, Chong] Univ Sao Paulo, Fac Med, Dept Pediat, Genet Unit,Inst Crianca,Hosp Clin, Sao Paulo, Brazil. [Alonso, Nivaldo] Univ Sao Paulo, Fac Med, Dept Surg, Div Plast Surg, Sao Paulo, Brazil. [Hart, Thomas] NIDCR, Human Craniofacial Genet Sect, NIH, Bethesda, MD USA. [Han, Sangwoo] NIDR, NIH, Bethesda, MD 20892 USA. [Stelini, Rafael F.] State Univ Campinas UNICAMP, Sch Med Sci, Dept Anat Pathol, Campinas, SP, Brazil. [Hart, P. Suzanne] NHGRI, Off Clin Director, NIH, Bethesda, MD 20892 USA. RP Raposo-Amaral, CE (reprint author), Brazilian Soc Res & Assistance Craniofacial Rehab, Inst Plast & Craniofacial Surg, Av Adolpho Lutz 100, BR-13094776 Campinas, SP, Brazil. EM cassioraposo@hotmail.com RI Denadai, Rafael/A-8038-2013; Raposo Amaral, Cassio Eduardo/D-1397-2013 OI Denadai, Rafael/0000-0003-0525-3480; Raposo Amaral, Cassio Eduardo/0000-0001-6201-0827 FU Intramural NIH HHS [Z99 HG999999] NR 30 TC 15 Z9 16 U1 0 U2 3 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1552-4825 J9 AM J MED GENET A JI Am. J. Med. Genet. A PD APR PY 2012 VL 158A IS 4 BP 732 EP 742 DI 10.1002/ajmg.a.35228 PG 11 WC Genetics & Heredity SC Genetics & Heredity GA 922JW UT WOS:000302544200008 PM 22383261 ER PT J AU Shi, M Murray, JC Marazita, ML Munger, RG Ruczinski, I Hetmanski, JB Wu, T Murray, T Redett, RJ Wilcox, AJ Lie, RT Jabs, EW Wu-Chou, YH Chen, PK Wang, H Ye, XQ Yeow, V Chong, SS Shi, B Christensen, K Scott, AF Patel, P Cheah, F Beaty, TH AF Shi, Min Murray, Jeffrey C. Marazita, Mary L. Munger, Ronald G. Ruczinski, Ingo Hetmanski, Jacqueline B. Wu, Tao Murray, Tanda Redett, Richard J. Wilcox, Allen J. Lie, Rolv T. Jabs, Ethylin Wang Wu-Chou, Yah Huei Chen, Philip K. Wang, Hong Ye, Xiaoqian Yeow, Vincent Chong, Samuel S. Shi, Bing Christensen, Kaare Scott, Alan F. Patel, Poorav Cheah, Felicia Beaty, Terri H. TI Genome Wide Study of Maternal and Parent-of-Origin Effects on the Etiology of Orofacial Clefts SO AMERICAN JOURNAL OF MEDICAL GENETICS PART A LA English DT Article DE GWAS; CL/P; CP; maternal genes; parent-of-origin; family-based study; association study ID LINKAGE DISEQUILIBRIUM; 4 POPULATIONS; FLIP-FLOP; PALATE; LIP; GENE; ASSOCIATION; RISK; TRANSMISSION; REVEALS AB We performed a genome wide association analysis of maternally-mediated genetic effects and parent-of-origin (POO) effects on risk of orofacial clefting (OC) using over 2,000 case-parent triads collected through an international cleft consortium. We used log-linear regression models to test individual SNPs. For SNPs with a P-value <10(-5) for maternal genotypic effects, we also applied a haplotype-based method, TRIMM, to extract potential information from clusters of correlated SNPs. None of the SNPs were significant at the genome wide level. Our results suggest neither maternal genome nor POO effects play major roles in the etiology of OC in our sample. This finding is consistent with previous genetic studies and recent population-based cohort studies in Norway and Denmark, which showed no apparent difference between mother-to-offspring and father-to-offspring recurrence of clefting. We, however, cannot completely rule out maternal genome or POO effects as risk factors because very small effects might not be detectable with our sample size, they may influence risk through interactions with environmental exposures or may act through a more complex network of interacting genes. Thus, the most promising SNPs identified by this study may still be worth further investigation. Published 2012. This article is a U.S. Government work and is in the public domain in the USA. C1 [Shi, Min] NIEHS, Biostat Branch, NIH, Durham, NC USA. [Murray, Jeffrey C.] Univ Iowa, Dept Pediat, Iowa City, IA 52242 USA. [Marazita, Mary L.] Univ Pittsburgh, Sch Dent Med, Dept Oral Biol, Pittsburgh, PA USA. [Munger, Ronald G.] Utah State Univ, Dept Nutr & Food Sci, Logan, UT 84322 USA. [Ruczinski, Ingo] Johns Hopkins Univ, Sch Publ Hlth, Dept Biostat, Baltimore, MD USA. [Hetmanski, Jacqueline B.; Wu, Tao; Murray, Tanda; Patel, Poorav; Beaty, Terri H.] Johns Hopkins Univ, Sch Med, Dept Epidemiol, Baltimore, MD USA. [Wu, Tao; Wang, Hong] Peking Univ, Hlth Sci Ctr, Sch Publ Hlth, Dept Epidemiol & Biostat, Beijing 100871, Peoples R China. [Redett, Richard J.] Johns Hopkins Univ, Dept Plast Surg, Sch Med, Baltimore, MD USA. [Wilcox, Allen J.] NIEHS, Epidemiol Branch N, NIH, Durham, NC USA. [Lie, Rolv T.] Univ Bergen, Dept Biostat, Bergen, Norway. [Jabs, Ethylin Wang; Scott, Alan F.] Johns Hopkins Univ, Inst Med Genet, Baltimore, MD USA. [Jabs, Ethylin Wang; Ye, Xiaoqian] Mt Sinai Sch Med, Dept Genet & Genom Sci, New York, NY USA. [Wu-Chou, Yah Huei; Chen, Philip K.] Chang Gung Mem Hosp, Human Mol Genet Lab, Tao Yuan, Taiwan. [Ye, Xiaoqian] Wuhan Univ, Sch Stomatol, Wuhan 430072, Peoples R China. [Yeow, Vincent] KK Womens & Childrens Hosp, Dept Plast Reconstruct & Anesthet Surg, Singapore, Singapore. [Chong, Samuel S.; Cheah, Felicia] Natl Univ Singapore, Natl Univ Hosp, Deparment Pediat, Singapore 117548, Singapore. [Shi, Bing] Sichuan Univ, W China Sch Stomatol, Chengdu 610064, Peoples R China. [Christensen, Kaare] Univ So Denmar, Odense, Denmark. RP Shi, M (reprint author), Natl Inst Environm Hlth Sci, Biostat Branch, Mail Drop A3-03 101-A352, Res Triangle Pk, NC 27709 USA. EM shi2@niehs.nih.gov RI Christensen, Kaare/C-2360-2009; Chong, Samuel/D-8098-2015; OI Christensen, Kaare/0000-0002-5429-5292; Wilcox, Allen/0000-0002-3376-1311; Jabs, Ethylin/0000-0001-8983-5466 FU National Institute for Dental and Craniofacial Research [U01-DE-018993, U01-DE-004425]; National Institute of Dental & Craniofacial Research [R21-DE-013707, R37-DE-08559, R01-DE-014581]; International Consortium to Identify Genes & Interactions Controlling Oral Clefts; TH Beaty, PI; NIH [D43 TW06176]; NIH, National Institute of Environmental Health Sciences FX Grant sponsor: National Institute for Dental and Craniofacial Research; Grant number: U01-DE-018993; Grant sponsor: National Institute of Dental & Craniofacial Research; Grant numbers: R21-DE-013707, R37-DE-08559, R01-DE-014581.; We sincerely thank all of the families at each recruitment site for participating in this study, and we gratefully acknowledge the invaluable assistance of clinical, field, and laboratory staff who contributed in making this work possible. The International Cleft Consortium including genotyping and analysis was supported by the National Institute for Dental and Craniofacial Research through U01-DE-004425; "International Consortium to Identify Genes & Interactions Controlling Oral Clefts", 2007-2009; TH Beaty, PI. This research was supported by R21-DE-013707, R37-DE-08559, R01-DE-014581 from the National Institute of Dental & Craniofacial Research. T. W. is supported by the International Collaborative Genetics Research Training Program (ICGRTP), NIH D43 TW06176. This research was also supported by the Intramural Research Program of the NIH, National Institute of Environmental Health Sciences. We thank the Smile Train Foundation for supporting cleft research in China and Operation Smile for research in the Philippines. NR 35 TC 10 Z9 11 U1 1 U2 10 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1552-4825 J9 AM J MED GENET A JI Am. J. Med. Genet. A PD APR PY 2012 VL 158A IS 4 BP 784 EP 794 DI 10.1002/ajmg.a.35257 PG 11 WC Genetics & Heredity SC Genetics & Heredity GA 922JW UT WOS:000302544200014 PM 22419666 ER PT J AU Voermans, NC Kempers, M Lammens, M van Alfen, N Janssen, MC Bonnemann, C van Engelen, BG Hamel, BC AF Voermans, N. C. Kempers, M. Lammens, M. van Alfen, N. Janssen, M. C. Bonnemann, C. van Engelen, B. G. Hamel, B. C. TI Myopathy in a 20-Year-Old Female Patient With D4ST-1 Deficient Ehlers-Danlos Syndrome Due to a Homozygous CHST14 Mutation SO AMERICAN JOURNAL OF MEDICAL GENETICS PART A LA English DT Article DE Ehlers-Danlos syndrome; myopathy; neuromuscular features; muscle biopsy; delayed motor development; connective tissue; CHST14; musculocontractural Ehlers-Danlos syndrome; adducted thumb-clubfoot syndrome ID MYOFASCIAL FORCE TRANSMISSION; THUMB-CLUBFOOT SYNDROME; GENITOPATELLAR SYNDROME; DIFFERENTIAL-DIAGNOSIS; SUPPORT OVERLAP; CONTRACTURES; JOINT; DYSTROPHY; VALUES; VIB AB We here report on a 20-year-old female patient with EDS due to a homozygous CHST14 single nucleotide deletion resulting in D4ST-1 deficiency, accompanied by muscle hypoplasia and muscle weakness. Findings of muscle ultrasound, electromyography, and muscle biopsy pointed to a myopathy, similarly as in other EDS types. This myopathy probably contributes to the gross motor developmental delay in this type of EDS. (C) 2012 Wiley Periodicals, Inc. C1 [Voermans, N. C.] Radboud Univ Nijmegen, Med Ctr, Donders Inst Brain Cognit & Behav, Dept Neurol, NL-6500 HB Nijmegen, Netherlands. [Kempers, M.; Hamel, B. C.] Radboud Univ Nijmegen, Med Ctr, Dept Human Genet, NL-6500 HB Nijmegen, Netherlands. [Lammens, M.] Radboud Univ Nijmegen, Med Ctr, Dept Pathol, NL-6500 HB Nijmegen, Netherlands. [van Alfen, N.] Radboud Univ Nijmegen, Med Ctr, Dept Clin Neurophysiol, NL-6500 HB Nijmegen, Netherlands. [Janssen, M. C.] Radboud Univ Nijmegen, Med Ctr, Dept Internal Med, NL-6500 HB Nijmegen, Netherlands. [Bonnemann, C.] NINDS, Neuromuscular & Neurogenet Disorders Childhood Se, Neurogenet Branch, NIH, Bethesda, MD 20892 USA. RP Voermans, NC (reprint author), Radboud Univ Nijmegen, Med Ctr, Donders Inst Brain Cognit & Behav, Dept Neurol, 935,POB 9101, NL-6500 HB Nijmegen, Netherlands. EM n.voermans@neuro.umcn.nl RI van Engelen, Baziel/D-3475-2009; van Alfen, Nens/J-6011-2012; Engelen, B.G.M./H-8027-2014; van Alfen, Nens/L-4172-2015; Voermans, N.C./L-4724-2015; Janssen, Mirian/D-9777-2016 OI Janssen, Mirian/0000-0003-4668-9977 FU Prinses Beatrix Fonds FX Grant sponsor: Prinses Beatrix Fonds. NR 32 TC 11 Z9 11 U1 0 U2 3 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1552-4825 J9 AM J MED GENET A JI Am. J. Med. Genet. A PD APR PY 2012 VL 158A IS 4 BP 850 EP 855 DI 10.1002/ajmg.a.35232 PG 6 WC Genetics & Heredity SC Genetics & Heredity GA 922JW UT WOS:000302544200025 PM 22407744 ER PT J AU Gilbert, SA Grobman, WA Landon, MB Spong, CY Rouse, DJ Leveno, KJ Varner, MW Caritis, SN Meis, PJ Sorokin, Y Carpenter, M O'Sullivan, MJ Sibai, BM Thorp, JM Ramin, SM Mercer, BM AF Gilbert, Sharon A. Grobman, William A. Landon, Mark B. Spong, Catherine Y. Rouse, Dwight J. Leveno, Kenneth J. Varner, Michael W. Caritis, Steve N. Meis, Paul J. Sorokin, Yoram Carpenter, Marshall O'Sullivan, Mary J. Sibai, Baha M. Thorp, John M. Ramin, Susan M. Mercer, Brian M. CA Eunice Kennedy Shriver Natl Inst C TI Elective repeat cesarean delivery compared with spontaneous trial of labor after a prior cesarean delivery: a propensity score analysis SO AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY LA English DT Article DE elective repeat cesarean delivery; propensity score; trial of labor ID UTERINE RUPTURE; VAGINAL BIRTH; OUTCOMES; SECTION; NUMBER; WOMEN; RISK AB OBJECTIVE: The purpose of this study was to determine outcomes, after the use of propensity score techniques, to create balanced groups according to whether a woman undergoes elective repeat cesarean delivery (ERCD) or trial of labor (TOL). STUDY DESIGN: Women who were eligible for a TOL with 1 previous low transverse incision were categorized according to whether they underwent an ERCD or TOL. A propensity score technique was used to develop ERCD and TOL groups with comparable baseline characteristics. Outcomes were assessed with conditional logistic regression. RESULTS: The rates of endometritis, operative injury, respiratory distress syndrome, and newborn infant infection were lower and the rates of hysterectomy and wound complication were higher in the ERCD group. CONCLUSION: Propensity score techniques can be used to generate comparable ERCD and TOL groups. Some types of maternal morbidity (such as hysterectomy) are higher; other types (such as operative injury) are lower in the ERCD group. Although the absolute risk is low, neonatal morbidity appears to be lower in the ERCD group. C1 [Gilbert, Sharon A.] George Washington Univ, Ctr Biostat, Washington, DC 20052 USA. [Grobman, William A.] Northwestern Univ, Dept Obstet, Chicago, IL 60611 USA. [Grobman, William A.] Northwestern Univ, Dept Gynecol, Chicago, IL 60611 USA. [Landon, Mark B.] Ohio State Univ, Columbus, OH 43210 USA. [Rouse, Dwight J.] Univ Alabama Birmingham, Birmingham, AL USA. [Leveno, Kenneth J.] Univ Texas SW Med Ctr Dallas, Dallas, TX 75390 USA. [Varner, Michael W.] Univ Utah, Salt Lake City, UT USA. [Meis, Paul J.] Wake Forest Univ Hlth Sci, Winston Salem, NC USA. [Sorokin, Yoram] Wayne State Univ, Detroit, MI USA. [Carpenter, Marshall] Brown Univ, Providence, RI 02912 USA. [O'Sullivan, Mary J.] Univ Miami, Miami, FL USA. [Sibai, Baha M.] Univ Tennessee, Memphis, TN USA. [Thorp, John M.] Univ N Carolina, Chapel Hill, NC USA. [Ramin, Susan M.] Univ Texas Hlth Sci Ctr Houston, Houston, TX USA. [Mercer, Brian M.] Case Western Reserve Univ, Metrohlth Med Ctr, Cleveland, OH USA. [Spong, Catherine Y.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Bethesda, MD USA. [Caritis, Steve N.] Univ Pittsburgh, Pittsburgh, PA USA. RP Gilbert, SA (reprint author), George Washington Univ, Ctr Biostat, Washington, DC 20052 USA. RI Varner, Michael/K-9890-2013 OI caritis, steve/0000-0002-2169-0712; Varner, Michael/0000-0001-9455-3973 FU Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) of the National Institutes of Health [HD21410, HD21414, HD27860, HD27861, HD27869, HD27905, HD27915, HD27917, HD34116, HD34122, HD34136, HD34208, HD34210, HD40500, HD40485, HD40544, HD40545, HD40560, HD40512, HD36801] FX Supported by grants from the Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) of the National Institutes of Health (HD21410, HD21414, HD27860, HD27861, HD27869, HD27905, HD27915, HD27917, HD34116, HD34122, HD34136, HD34208, HD34210, HD40500, HD40485, HD40544, HD40545, HD40560, HD40512, and HD36801) and its contents are solely the responsibility of the authors and do not necessarily represent the official view of National Institute of Child Health and Human Development or the National Institutes of Health. NR 29 TC 6 Z9 6 U1 2 U2 5 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0002-9378 J9 AM J OBSTET GYNECOL JI Am. J. Obstet. Gynecol. PD APR PY 2012 VL 206 IS 4 AR 311.e1 DI 10.1016/j.ajog.2012.02.002 PG 9 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 918QS UT WOS:000302266000016 PM 22464069 ER PT J AU Kakani, S Yardeni, T Poling, J Ciccone, C Niethamer, T Klootwijk, ED Manoli, I Darvish, D Hoogstraten-Miller, S Zerfas, P Tian, E Ten Hagen, KG Kopp, JB Gahl, WA Huizing, M AF Kakani, Sravan Yardeni, Tal Poling, Justin Ciccone, Carla Niethamer, Terren Klootwijk, Enriko D. Manoli, Irini Darvish, Daniel Hoogstraten-Miller, Shelley Zerfas, Patricia Tian, E. Ten Hagen, Kelly G. Kopp, Jeffrey B. Gahl, William A. Huizing, Marjan TI The Gne M712T Mouse as a Model for Human Glomerulopathy SO AMERICAN JOURNAL OF PATHOLOGY LA English DT Article ID ACETYLGLUCOSAMINE 2-EPIMERASE/N-ACETYLMANNOSAMINE KINASE; SIALIC-ACID BIOSYNTHESIS; HELIX-POMATIA AGGLUTININ; INCLUSION-BODY MYOPATHY; N-ACETYLNEURAMINIC ACID; AMINONUCLEOSIDE NEPHROSIS; ACTIN CYTOSKELETON; EPITHELIAL-CELL; MEMBRANOUS GLOMERULONEPHRITIS; AFFINITY-CHROMATOGRAPHY AB Pathological glomerular hyposialylation has been implicated in certain unexplained glomerulopathies, including minimal change nephrosis, membranous glomerulonephritis, and IgA nephropathy. We studied our previously established mouse model carrying a homozygous mutation in the key enzyme of sialic acid biosynthesis, N-acetylglucosamine 2-epimerase/N-acetylmannosamine kinase. Mutant mice died before postnatal day 3 (P3) from severe glomerulopathy with podocyte effacement and segmental glomerular basement membrane splitting due to hyposialylation. Administration of the sialic acid precursor N-acetylmannosamine (ManNAc) led to improved sialylation and survival of mutant pups beyond P3. We determined the onset of the glomerulopathy in the embryonic stage. A lectin panel, distinguishing normally sialylated from hyposialylated glycans, used WGA, SNA, PNA, Jacalin, HPA, and VVA, indicating glomerular hyposialylation of predominantly O-linked glycoproteins in mutant mice. The glomerular glycoproteins nephrin and podocalyxin were hyposialylated in this unique murine model. ManNAc treatment appeared to ameliorate the hyposialylation status of mutant mice, indicated by a lectin histochemistry pattern similar to that of wild-type mice, with improved sialylation of both nephrin and podocalyxin, as well as reduced albuminuria compared with untreated mutant mice. These findings suggest application of our lectin panel for categorizing human kidney specimens based on glomerular sialylation status. Moreover, the partial restoration of glomerular architecture in ManNAc-treated mice highlights ManNAc as a potential treatment for humans affected with disorders of glomerular hyposialylation. (Am J Pathol 2012, 180:1431-1444; DOI: 10.1016/j.ajpath.2011.12.023) C1 [Huizing, Marjan] NHGRI, Cell Biol Metab Disorders Unit, Med Genet Branch, NIH, Bethesda, MD 20892 USA. [Hoogstraten-Miller, Shelley] NHGRI, Off Lab Anim Med, Bethesda, MD 20892 USA. [Manoli, Irini; Gahl, William A.] Natl Inst Dent & Craniofacial Res, Off Rare Dis Res, Off Director, Bethesda, MD USA. [Zerfas, Patricia] Natl Inst Dent & Craniofacial Res, Div Vet Resources, Bethesda, MD USA. [Tian, E.; Ten Hagen, Kelly G.] Natl Inst Dent & Craniofacial Res, Dev Glycobiol Unit, Off Res Serv, Bethesda, MD USA. [Kopp, Jeffrey B.] NIDDK, Kidney Dis Sect, NIH, Bethesda, MD USA. [Yardeni, Tal] Tel Aviv Univ, Sackler Sch Med, Grad Partner Program, IL-69978 Tel Aviv, Israel. [Poling, Justin] Howard Hughes Med Inst, Chevy Chase, MD USA. [Klootwijk, Enriko D.] UCL, Dept Med, London, England. [Darvish, Daniel] HIBM Res Grp, Encino, CA USA. RP Huizing, M (reprint author), NHGRI, Cell Biol Metab Disorders Unit, Med Genet Branch, NIH, Bethesda, MD 20892 USA. EM mhuizing@mail.nih.gov OI Manoli, Irini/0000-0003-1543-2941; Kopp, Jeffrey/0000-0001-9052-186X FU National Human Genome Research Institute; National Dental and Craniofacial Research Institute; National Institute of Diabetes and Digestive and Kidney Diseases, NIH, Bethesda, MD FX Supported by the Intramural Research Programs of the National Human Genome Research Institute, the National Dental and Craniofacial Research Institute, and the National Institute of Diabetes and Digestive and Kidney Diseases, NIH, Bethesda, MD. NR 82 TC 10 Z9 10 U1 0 U2 3 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0002-9440 J9 AM J PATHOL JI Am. J. Pathol. PD APR PY 2012 VL 180 IS 4 BP 1431 EP 1440 DI 10.1016/j.ajpath.2011.12.023 PG 10 WC Pathology SC Pathology GA 919LO UT WOS:000302329400013 PM 22322304 ER PT J AU Howden, R Cho, HY Miller-DeGraff, L Walker, C Clark, JA Myers, PH Rouse, DC Kleeberger, SR AF Howden, Reuben Cho, Hye-Youn Miller-DeGraff, Laura Walker, Christopher Clark, James A. Myers, Page H. Rouse, D. Clay Kleeberger, Steven R. TI Cardiac Physiologic and Genetic Predictors of Hyperoxia-Induced Acute Lung Injury in Mice SO AMERICAN JOURNAL OF RESPIRATORY CELL AND MOLECULAR BIOLOGY LA English DT Article DE heart rate; hyperoxia; genome-wide mapping ID HEART-RATE-VARIABILITY; NRF2; RESPONSES; STRESS; OXYGEN; SUSCEPTIBILITY; INHALATION; INDUCTION; DYSPLASIA; PROTEINS AB Exposure of mice to hyperoxia produces pulmonary toxicity similar to acute lung injury/acute respiratory distress syndrome, but little is known about the interactions within the cardiopulmonary system. This study was designed to characterize the cardiopulmonary response to hyperoxia, and to identify candidate susceptibility genes in mice. Electrocardiogram and ventilatory data were recorded continuously from 4 inbred and 29 recombinant inbred strains during 96 hours of hyperoxia (100% oxygen). Genome-wide linkage analysis was performed in 27 recombinant inbred strains against response time indices (TIs) calculated from each cardiac phenotype. Reductions in minute ventilation, heart rate (HR), low-frequency(LF) HR variability (HRV), high-frequency HRV, and total power HRV were found in all mice during hyperoxia exposure, but the lag time before these changes began was strain dependent. Significant (chromosome 9) or suggestive (chromosomes 3 and 5) quantitative trait loci were identified for the HRTI and LFTI. Functional polymorphisms in several candidate susceptibility genes were identified within the quantitative trait loci and were associated with hyperoxia susceptibility. This is the first study to report highly significant interstrain variation in hyperoxia-induced changes in minute ventilation, HR, and HRV, and to identify polymorphisms in candidate susceptibility genes that associate with cardiac responses. Results indicate that changes in HR and LF HRV could be important predictors of subsequent adverse outcome during hyperoxia exposure, specifically the pathogenesis of acute lung injury. Understanding the genetic mechanisms of these responses may have significant diagnostic clinical value. C1 [Howden, Reuben] Univ N Carolina, Dept Kinesiol, Charlotte, NC 28223 USA. [Cho, Hye-Youn; Miller-DeGraff, Laura; Walker, Christopher; Kleeberger, Steven R.] Natl Inst Environm Hlth Sci, Lab Resp Biol, NIH, Res Triangle Pk, NC USA. [Clark, James A.; Myers, Page H.] Natl Inst Environm Hlth Sci, Comparat Med Branch, NIH, Res Triangle Pk, NC USA. [Rouse, D. Clay] Duke Univ, Med Ctr, Div Lab Anim Resources, Durham, NC USA. RP Howden, R (reprint author), Univ N Carolina, Dept Kinesiol, Charlotte, NC 28223 USA. EM rhowden@uncc.edu FU National Institute of Environmental Health Sciences, National Institutes of Health, Department of Health and Human Services FX This work was supported by the Intramural Research Program of the National Institute of Environmental Health Sciences, National Institutes of Health, Department of Health and Human Services. NR 30 TC 9 Z9 9 U1 0 U2 0 PU AMER THORACIC SOC PI NEW YORK PA 61 BROADWAY, FL 4, NEW YORK, NY 10006 USA SN 1044-1549 J9 AM J RESP CELL MOL JI Am. J. Respir. Cell Mol. Biol. PD APR PY 2012 VL 46 IS 4 BP 470 EP 478 DI 10.1165/rcmb.2011-0204OC PG 9 WC Biochemistry & Molecular Biology; Cell Biology; Respiratory System SC Biochemistry & Molecular Biology; Cell Biology; Respiratory System GA 924LC UT WOS:000302691900008 PM 22052878 ER PT J AU Guindo, MA Shott, JP Saye, R Diakite, ML Sanogo, S Dembele, MB Keita, S Nagel, MC Ellis, RD Aebig, JA Diallo, DA Doumbo, OK AF Guindo, Merepen A. Shott, Joseph P. Saye, Renion Diakite, Moussa L. Sanogo, Sintry Dembele, Moussa B. Keita, Sekouba Nagel, Mary C. Ellis, Ruth D. Aebig, Joan A. Diallo, Dapa A. Doumbo, Ogobara K. TI Promoting Good Clinical Laboratory Practices and Laboratory Accreditation to Support Clinical Trials in Sub-Saharan Africa SO AMERICAN JOURNAL OF TROPICAL MEDICINE AND HYGIENE LA English DT Article ID MALARIA VACCINE; FALCIPARUM-MALARIA; MALI; CHILDREN; PHASE-2; VILLAGE; ANEMIA AB Laboratory capacity in the developing world frequently lacks quality management systems (QMS) such as good clinical laboratory practices, proper safety precautions, and adequate facilities; impacting the ability to conduct biomedical research where it is needed most. As the regulatory climate changes globally, higher quality laboratory support is needed to protect study volunteers and to accurately assess biological parameters. The University of Bamako and its partners have undertaken a comprehensive QMS plan to improve quality and productivity using the Clinical and Laboratory Standards Institute standards and guidelines. The clinical laboratory passed the College of American Pathologists inspection in April 2010, and received full accreditation in June 2010. Our efforts to implement high-quality standards have been valuable for evaluating safety and immunogenicity of malaria vaccine candidates in Mali. Other disease-specific research groups in resource-limited settings may benefit by incorporating similar training initiatives, QMS methods, and continual improvement practices to ensure best practices. C1 [Guindo, Merepen A.; Diakite, Moussa L.; Sanogo, Sintry; Dembele, Moussa B.; Keita, Sekouba; Diallo, Dapa A.; Doumbo, Ogobara K.] Univ Bamako, Malaria Res & Training Ctr, Mali ICER, Bamako, Mali. [Shott, Joseph P.] NIAID, OD, DIR, Bethesda, MD 20892 USA. [Saye, Renion] USAID Mali, Bamako, Mali. [Nagel, Mary C.] Minist Hlth, Lab Natl Sante Publ, Port Au Prince, Haiti. NIAID, LMIV, DIR, NIH, Rockville, MD USA. NCI, Clin Monitoring Res Program, SAIC Frederick Inc, Frederick, MD 21701 USA. GHP, CLSI, Wayne, PA USA. Univ Bamako, MRTC, FMPOS, Mali Int Ctr Excellence Res ICER, Bamako, Mali. RP Shott, JP (reprint author), 33 North Dr,MSC 3207, Bethesda, MD 20892 USA. EM agnes@icermali.org; ShottJ@mail.nih.gov; saye@icermali.org; mldiakite@icermali.org; ssanogo@icermali.org; moussab@icermali.org; Sekouba@icermali.org; mcnagel@live.com; ellisru@niaid.nih.gov; jaebig@niaid.nih.gov; dadiallo@icermali.org; okd@icermali.org FU Division of Intramural Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health; National Cancer Institute, National Institutes of Health [HHSN261200800001E]; National Institute of Allergy and Infectious Diseases FX The clinical laboratory is financially supported by the Division of Intramural Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health. This project has been funded in whole or in part with federal funds from the National Cancer Institute, National Institutes of Health, under contract no. HHSN261200800001E. This research was supported (in part) by the National Institute of Allergy and Infectious Diseases. NR 15 TC 6 Z9 8 U1 0 U2 0 PU AMER SOC TROP MED & HYGIENE PI MCLEAN PA 8000 WESTPARK DR, STE 130, MCLEAN, VA 22101 USA SN 0002-9637 J9 AM J TROP MED HYG JI Am. J. Trop. Med. Hyg. PD APR PY 2012 VL 86 IS 4 BP 573 EP 579 DI 10.4269/ajtmh.2012.11-0691 PG 7 WC Public, Environmental & Occupational Health; Tropical Medicine SC Public, Environmental & Occupational Health; Tropical Medicine GA 922AR UT WOS:000302519700005 PM 22492138 ER PT J AU Valerio, L Facchinelli, L Ramsey, JM Scott, TW AF Valerio, Laura Facchinelli, Luca Ramsey, Janine M. Scott, Thomas W. TI Dispersal of Male Aedes aegypti in a Coastal Village in Southern Mexico SO AMERICAN JOURNAL OF TROPICAL MEDICINE AND HYGIENE LA English DT Article ID DENGUE VECTOR MOSQUITOS; RELEASE-RECAPTURE; SURVIVAL RATES; BORNE DISEASES; BODY-SIZE; POPULATION; CULICIDAE; DIPTERA; THAILAND; ALBOPICTUS AB Most Aedes aegypti dispersal studies have focused on females because of their central role in dengue virus transmission. Only a few mark-release-recapture (MRR) studies provided insights into male Ae. aegypti dispersal. To fill this knowledge gap, we conducted five male Ae. aegypti MRR experiments in a coastal village in southern Mexico. Small and large male cohorts were marked with fluorescent dusts, released outside buildings, and recaptures were carried out by using backpack aspirators. Recapture rates ranged between 0.35% and 6.55% and median distance traveled was 12-166 meters. A statistically significant difference in median distance traveled with large males dispersing farther than small ones was detected only in one experiment (MRR5: U = 3.5, P < 0.01). Male dispersal data will be useful for constructing and estimating parameter values and validating models that will be used to plan the most effective release strategies for genetically modified male Ae. aegypti. C1 [Valerio, Laura; Facchinelli, Luca; Scott, Thomas W.] Univ Calif Davis, Dept Entomol, Davis, CA 95616 USA. [Valerio, Laura] Univ Roma La Sapienza, Inst Pasteur, Cenci Bolognetti Fdn, Rome, Italy. [Ramsey, Janine M.] INSP, Ctr Reg Invest Salud Publ, Tapachula 30700, Chiapas, Mexico. [Scott, Thomas W.] NIH, Fogarty Int Ctr, Bethesda, MD 20892 USA. RP Valerio, L (reprint author), Univ Calif Davis, Dept Entomol, Davis, CA 95616 USA. EM lvalerio@ucdavis.edu; lfacchinelli@ucdavis.edu; jramsey@insp.mx; twscott@ucdavis.edu OI Facchinelli, Luca/0000-0002-8987-1472 FU Pasteur Institute-Cenci Bolognetti Foundation; Foundation for the National Institutes of Health [316] FX This study was supported by the Pasteur Institute-Cenci Bolognetti Foundation and the Foundation for the National Institutes of Health through the Grand Challenges in Global Health Initiative (GC7 #316). NR 41 TC 13 Z9 13 U1 0 U2 21 PU AMER SOC TROP MED & HYGIENE PI MCLEAN PA 8000 WESTPARK DR, STE 130, MCLEAN, VA 22101 USA SN 0002-9637 J9 AM J TROP MED HYG JI Am. J. Trop. Med. Hyg. PD APR PY 2012 VL 86 IS 4 BP 665 EP 676 DI 10.4269/ajtmh.2012.11-0513 PG 12 WC Public, Environmental & Occupational Health; Tropical Medicine SC Public, Environmental & Occupational Health; Tropical Medicine GA 922AR UT WOS:000302519700019 PM 22492152 ER PT J AU Yeh, S Fahle, G Flaxel, CJ Francis, PJ AF Yeh, Steven Fahle, Gary Flaxel, Christina J. Francis, Peter J. TI Central Retinal Vascular Occlusion Associated With Acute Retinal Necrosis SO ARCHIVES OF OPHTHALMOLOGY LA English DT Editorial Material C1 [Flaxel, Christina J.; Francis, Peter J.] Oregon Hlth & Sci Univ, Casey Eye Inst, Portland, OR 97239 USA. [Yeh, Steven] Emory Univ, Sch Med, Emory Eye Ctr, Atlanta, GA USA. [Fahle, Gary] NIH, Dept Lab Med, Bethesda, MD 20892 USA. RP Francis, PJ (reprint author), Oregon Hlth & Sci Univ, Casey Eye Inst, 3375 SW Terwilliger Blvd, Portland, OR 97239 USA. EM francisp@ohsu.edu NR 7 TC 2 Z9 2 U1 0 U2 3 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60654-0946 USA SN 0003-9950 J9 ARCH OPHTHALMOL-CHIC JI Arch. Ophthalmol. PD APR PY 2012 VL 130 IS 4 BP 514 EP 517 PG 4 WC Ophthalmology SC Ophthalmology GA 922OK UT WOS:000302557100016 PM 22491922 ER PT J AU Varga, T Mogyorodi, B Bago, AG Cservenak, M Domokos, D Renner, E Gallatz, K Usdin, TB Palkovits, M Dobolyi, A AF Varga, Tamas Mogyorodi, Bence Bago, Attila G. Cservenak, Melinda Domokos, Dominika Renner, Eva Gallatz, Katalin Usdin, Ted B. Palkovits, Miklos Dobolyi, Arpad TI Paralemniscal TIP39 is induced in rat dams and may participate in maternal functions SO BRAIN STRUCTURE & FUNCTION LA English DT Article DE Tuberoinfundibular peptide of 39 residues; Parathyroid hormone 2 receptor; Medial paralemniscal nucleus; Formalin pain stress; A7 noradrenergic cell group; Pontine tegmentum; Suckling ID ECHOLOCATING HORSESHOE BATS; CATECHOLAMINE CELL GROUP; TUBEROINFUNDIBULAR PEPTIDE; 39 RESIDUES; PERIAQUEDUCTAL GRAY; NERVOUS-SYSTEM; C-FOS; RETICULAR-FORMATION; PROLACTIN-RELEASE; SQUIRREL-MONKEY AB The paralemniscal area, situated between the pontine reticular formation and the lateral lemniscus in the pontomesencephalic tegmentum contains some tuberoinfundibular peptide of 39 residues (TIP39)-expressing neurons. In the present study, we measured a 4 times increase in the level of TIP39 mRNA in the paralemniscal area of lactating mothers as opposed to nulliparous females and mothers deprived of pups using real-time RT-PCR. In situ hybridization histochemistry and immunolabeling demonstrated that the induction of TIP39 in mothers takes place within the medial paralemniscal nucleus, a cytoarchitectonically distinct part of the paralemniscal area, and that the increase in TIP39 mRNA levels translates into elevated peptide levels in dams. The paralemniscal area has been implicated in maternal control as well as in pain perception. To establish the function of induced TIP39, we investigated the activation of TIP39 neurons in response to pup exposure as maternal, and formalin injection as noxious stimulus. Both stimuli elicited c-fos expression in the paralemniscal area. Subsequent double labeling demonstrated that 95% of neurons expressing Fos in response to pup exposure also contained TIP39 immunoreactivity and 91% of TIP39 neurons showed c-fos activation by pup exposure. In contrast, formalin-induced Fos does not co-localize with TIP39. Instead, most formalin-activated neurons are situated medial to the TIP39 cell group. Our data indicate that paralemniscal neurons may be involved in the processing of maternal and nociceptive information. However, two different groups of paralemniscal neurons participate in the two functions. In particular, TIP39 neurons may participate in the control of maternal functions. C1 [Varga, Tamas; Mogyorodi, Bence; Bago, Attila G.; Cservenak, Melinda; Domokos, Dominika; Renner, Eva; Gallatz, Katalin; Palkovits, Miklos; Dobolyi, Arpad] Semmelweis Univ, Neuromorphol & Neuroendocrine Res Lab, Dept Anat Histol & Embryol, H-1094 Budapest, Hungary. [Bago, Attila G.] Natl Inst Neurosurg, Budapest, Hungary. [Usdin, Ted B.] NIMH, Sect Fundamental Neurosci, Bethesda, MD 20892 USA. RP Dobolyi, A (reprint author), Semmelweis Univ, Neuromorphol & Neuroendocrine Res Lab, Dept Anat Histol & Embryol, Tuzolto 58, H-1094 Budapest, Hungary. EM dobolyi@ana.sote.hu RI Palkovits, Miklos/F-2707-2013; OI Palkovits, Miklos/0000-0003-0578-0387 FU Hungarian Academy of Sciences; Hungarian Science Foundation NKTH-OTKA [K67646]; Hungarian Science Foundation OTKA [CK80180]; NIMH; [OTKA K100319]; [OTKA NNF85612] FX Support was provided by the Bolyai Award of the Hungarian Academy of Sciences, the Hungarian Science Foundation NKTH-OTKA K67646, OTKA K100319, and OTKA NNF85612 research grants for AD, the Hungarian Science Foundation OTKA CK80180 research grant for MP, and the NIMH Intramural Research Program for TBU. We are grateful for the technical assistance of Szilvia Deak and Nikolett Hanak. NR 53 TC 4 Z9 4 U1 0 U2 8 PU SPRINGER HEIDELBERG PI HEIDELBERG PA TIERGARTENSTRASSE 17, D-69121 HEIDELBERG, GERMANY SN 1863-2653 J9 BRAIN STRUCT FUNCT JI Brain Struct. Funct. PD APR PY 2012 VL 217 IS 2 BP 323 EP 335 DI 10.1007/s00429-011-0357-2 PG 13 WC Anatomy & Morphology; Neurosciences SC Anatomy & Morphology; Neurosciences & Neurology GA 922UG UT WOS:000302573200011 PM 22081168 ER PT J AU Auner, HW Pavlu, J Szydlo, R Giles, C Kanfer, E Macdonald, D Marin, D Milojkovic, D Rezvani, K Goldman, JM Apperley, JF Landgren, O Rahemtulla, A AF Auner, Holger W. Pavlu, Jiri Szydlo, Richard Giles, Chrissy Kanfer, Ed Macdonald, Donald Marin, David Milojkovic, Dragana Rezvani, Katayoun Goldman, John M. Apperley, Jane F. Landgren, Ola Rahemtulla, Amin TI Autologous haematopoietic stem cell transplantation in multiple myeloma patients from ethnic minority groups in an equal access healthcare system SO BRITISH JOURNAL OF HAEMATOLOGY LA English DT Letter DE multiple myeloma; stem cell transplantation; ethnicity; race ID RACE; CHEMOTHERAPY; OUTCOMES C1 [Auner, Holger W.; Pavlu, Jiri; Szydlo, Richard; Giles, Chrissy; Kanfer, Ed; Macdonald, Donald; Marin, David; Milojkovic, Dragana; Rezvani, Katayoun; Goldman, John M.; Apperley, Jane F.; Rahemtulla, Amin] Univ London Imperial Coll Sci Technol & Med, Hammersmith Hosp, Ctr Haematol, London, England. [Auner, Holger W.] Univ London Imperial Coll Sci Technol & Med, Ctr Clin Sci, MRC, London, England. [Landgren, Ola] NCI, Multiple Myeloma Sect, Med Oncol Branch, Ctr Canc Res,NIH, Bethesda, MD 20892 USA. RP Auner, HW (reprint author), Univ London Imperial Coll Sci Technol & Med, Hammersmith Hosp, Ctr Haematol, London, England. EM holger.auner@csc.mrc.ac.uk; a.rahemtulla@imperial.ac.uk RI Szydlo, Richard/C-6678-2012; OI Szydlo, Richard/0000-0003-1102-8298; Auner, Holger/0000-0003-4040-0642 FU Medical Research Council [MC_G0802523] NR 10 TC 3 Z9 3 U1 0 U2 0 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0007-1048 J9 BRIT J HAEMATOL JI Br. J. Haematol. PD APR PY 2012 VL 157 IS 1 BP 125 EP 127 DI 10.1111/j.1365-2141.2011.08906.x PG 3 WC Hematology SC Hematology GA 907RZ UT WOS:000301436700015 PM 22050411 ER PT J AU Sherman, ME Figueroa, JD Henry, JE Clare, SE Rufenbarger, C Storniolo, AM AF Sherman, Mark E. Figueroa, Jonine D. Henry, Jill E. Clare, Susan E. Rufenbarger, Connie Storniolo, Anna Maria TI The Susan G. Komen for the Cure Tissue Bank at the IU Simon Cancer Center: A Unique Resource for Defining the "Molecular Histology" of the Breast SO CANCER PREVENTION RESEARCH LA English DT Article ID ESTROGEN-RECEPTOR EXPRESSION; RISK-FACTORS; INTERVAL; WOMEN; AGE; INVOLUTION; PHENOTYPE; MORTALITY; PREGNANCY; THERAPY AB "Molecular histology" of the breast may be conceptualized as encompassing the normative ranges of histologic structure and marker expression in normal breast tissues in relation to a woman's age and life experiences. Studies of molecular histology can aid our understanding of early events in breast carcinogenesis and provide data for comparison with diseased breast tissues. Until recently, lack of epidemiologically annotated, optimally prepared normal breast tissues obtained from healthy women presented a barrier to breast cancer research. The Komen Tissue Bank at Indiana University (Indianapolis, IN) is a unique biorepository that was developed to overcome this limitation. The Bank enrolls healthy donors who provide questionnaire data, blood, and up to four breast biopsies, which are prepared as both formalin-fixed, paraffin-embedded and frozen tissues. The resource is accessible to researchers worldwide through a proposal submission, review, and approval process. As of November 2010, the Bank had collected specimens and information from 1,174 donors. In this review, we discuss the importance of studying normal breast tissues, assess the strengths and limitations of studying normal tissues obtained from different sources, and summarize the features of the Komen Tissue Bank. As research projects are completed, results will be posted on the Bank's website. Cancer Prev Res; 5(4); 528-35. (C) 2012 AACR. C1 [Sherman, Mark E.; Figueroa, Jonine D.] NCI, Div Canc Epidemiol & Genet, Hormonal & Reprod Epidemiol Branch, Rockville, MD USA. [Henry, Jill E.; Clare, Susan E.; Rufenbarger, Connie; Storniolo, Anna Maria] Indiana Univ, Sch Med, IU Simon Canc Ctr, Susan G Komen Cure Tissue Bank, Indianapolis, IN 46202 USA. [Clare, Susan E.] Indiana Univ, Sch Med, Dept Surg, Div Breast Surg Oncol, Indianapolis, IN 46202 USA. [Storniolo, Anna Maria] Indiana Univ, Sch Med, Dept Med, Div Hematol Oncol, Indianapolis, IN 46202 USA. [Rufenbarger, Connie] Catherine Peachey Fund Inc, Warsaw, IN USA. RP Storniolo, AM (reprint author), Indiana Univ, Sch Med, Melvin & Bren Simon Canc Ctr, 535 Barnhill Dr,Room 473, Indianapolis, IN 46202 USA. EM astornio@iupui.edu FU Susan G. Komen for the Cure; Breast Cancer Research Foundation; Oracle Giving; Catherine Peachey Fund, Inc.; National Cancer Institute FX This study was supported by Susan G. Komen for the Cure; the Breast Cancer Research Foundation; Oracle Giving; the Catherine Peachey Fund, Inc.; and National Cancer Institute, Intramural Research Program. NR 34 TC 15 Z9 15 U1 0 U2 2 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1940-6207 J9 CANCER PREV RES JI Cancer Prev. Res. PD APR PY 2012 VL 5 IS 4 BP 528 EP 535 DI 10.1158/1940-6207.CAPR-11-0234 PG 8 WC Oncology SC Oncology GA 922TY UT WOS:000302572400007 PM 22345117 ER PT J AU Vitale-Cross, L Molinolo, AA Martin, D Younis, RH Maruyama, T Patel, V Chen, WJ Schneider, A Gutkind, JS AF Vitale-Cross, Lynn Molinolo, Alfredo A. Martin, Daniel Younis, Rania H. Maruyama, Takashi Patel, Vyomesh Chen, Wanjun Schneider, Abraham Gutkind, J. Silvio TI Metformin Prevents the Development of Oral Squamous Cell Carcinomas from Carcinogen-Induced Premalignant Lesions SO CANCER PREVENTION RESEARCH LA English DT Article ID BREAST-CANCER CELLS; NECK-CANCER; MAMMALIAN TARGET; ANTIDIABETIC DRUG; MTOR INHIBITION; CYCLE ARREST; IN-VITRO; HEAD; RAPAMYCIN; KINASE AB Head and neck squamous cell carcinoma (HNSCC) is a major public health concern. The recent identification of the mTOR complex 1 (mTORC1) signaling pathway as a highly prevalent molecular signature underlying HNSCC pathogenesis has provided the foundation to search for novel therapeutic approaches to prevent and treat HNSCC. Here, we asked whether metformin, the most widely used medication for the treatment of type II diabetes, which acts in part by stimulating the AMP-activated protein kinase (AMPK) signaling pathway thereby reducing mTORC1 activity, may lower the risk of HNSCC development. Indeed, we show that metformin reduces the growth of HNSCC cells and diminishes their mTORC1 activity by both AMPK-dependent and -independent mechanisms. We also optimized an oral-specific carcinogenesis mouse model that results in the accumulation of multiple oral premalignant lesions at the end of the carcinogen exposure, some of which then spontaneously progress into HNSCC. Using this mouse model, we observed that metformin specifically inhibits mTORC1 in the basal proliferating epithelial layer of oral premalignant lesions. Remarkably, metformin prevented the development of HNSCC by reducing significantly the size and number of carcinogen-induced oral tumoral lesions and by preventing their spontaneous conversion to squamous cell carcinomas. Collectively, our data underscore the potential clinical benefits of using metformin as a targeted chemopreventive agent in the control of HNSCC development and progression. Cancer Prev Res; 5(4); 562-73. (C) 2012 AACR. C1 [Vitale-Cross, Lynn; Molinolo, Alfredo A.; Martin, Daniel; Patel, Vyomesh; Gutkind, J. Silvio] Natl Inst Dent & Craniofacial Res, Mol Carcinogenesis Sect, Oral & Pharyngeal Canc Branch, NIH, Bethesda, MD 20892 USA. [Maruyama, Takashi; Chen, Wanjun] Natl Inst Dent & Craniofacial Res, Oral Mucosal Immunol Sect, Oral Infect & Immun Branch, NIH, Bethesda, MD 20892 USA. [Younis, Rania H.; Schneider, Abraham] Univ Maryland, Sch Dent, Dept Oncol & Diagnost Sci, Baltimore, MD 21201 USA. [Schneider, Abraham] Univ Maryland, Program Oncol, Greenebaum Canc Ctr, Baltimore, MD 21201 USA. RP Gutkind, JS (reprint author), Natl Inst Dent & Craniofacial Res, Mol Carcinogenesis Sect, Oral & Pharyngeal Canc Branch, NIH, 30 Convent Dr, Bethesda, MD 20892 USA. EM aschneider@umaryland.edu; sg39v@nih.gov FU NIH, National Institute of Dental and Craniofacial Research [Z01DE00558]; University of Maryland; JSPS at NIH FX This article was supported by the Intramural Research Program of the NIH, National Institute of Dental and Craniofacial Research, project Z01DE00558, and by the University of Maryland (to R.H. Younis and A. Schneider). T. Maruyama was supported in part by a JSPS Research Fellowship for Japanese Biomedical and Behavioral Researchers at NIH. NR 40 TC 46 Z9 49 U1 0 U2 2 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1940-6207 J9 CANCER PREV RES JI Cancer Prev. Res. PD APR PY 2012 VL 5 IS 4 BP 562 EP 573 DI 10.1158/1940-6207.CAPR-11-0502 PG 12 WC Oncology SC Oncology GA 922TY UT WOS:000302572400011 PM 22467081 ER PT J AU Messing, E Gee, JR Saltzstein, DR Kim, K diSant'Agnese, A Kolesar, J Harris, L Faerber, A Havighurst, T Young, JM Efros, M Getzenberg, RH Wheeler, MA Tangrea, J Parnes, H House, M Busby, JE Hohl, R Bailey, H AF Messing, Edward Gee, Jason R. Saltzstein, Daniel R. Kim, KyungMann diSant'Agnese, Anthony Kolesar, Jill Harris, Linda Faerber, Adrienne Havighurst, Thomas Young, Jay M. Efros, Mitchell Getzenberg, Robert H. Wheeler, Marcia A. Tangrea, Joseph Parnes, Howard House, Margaret Busby, J. Erik Hohl, Raymond Bailey, Howard TI A Phase 2 Cancer Chemoprevention Biomarker Trial of Isoflavone G-2535 (Genistein) in Presurgical Bladder Cancer Patients SO CANCER PREVENTION RESEARCH LA English DT Article ID TRANSITIONAL-CELL-CARCINOMA; PURIFIED SOY ISOFLAVONES; SINGAPORE CHINESE HEALTH; AKT SIGNALING PATHWAY; PROSTATE-CANCER; BREAST-CANCER; PROTEIN-KINASES; INCREASED RISK; DIETARY SOY; KAPPA-B AB The soy compound genistein has been observed preclinically to inhibit bladder cancer growth with one potential mechanism being the inhibition of epidermal growth factor receptor phosphorylation (p-EGFR). A phase 2 randomized, placebo-controlled trial investigated whether daily, oral genistein (300 or 600 mg/d as the purified soy extract G-2535) for 14 to 21 days before surgery alters molecular pathways in bladder epithelial tissue in 59 subjects diagnosed with urothelial bladder cancer (median age, 71 years). G-2535 treatment was well tolerated; observed toxicities were primarily mild to moderate gastrointestinal or metabolic and usually not attributed to study drug. Genistein was detected in plasma and urine of subjects receiving G-2535 at concentrations greater than placebo subjects' but were not dose-dependent. Reduction in bladder cancer tissue p-EGFR staining between the placebo arm and the combined genistein arms was significant at the protocol-specified significance level of 0.10 (P = 0.07). This difference was most prominent when comparing the 300-mg group with placebo (P = 0.015), but there was no significant reduction in p-EGFR staining between the 600-mg group and placebo. No difference in normal bladder epithelium p-EGFR staining was observed between treatment groups. No significant differences in tumor tissue staining between treatment groups were observed for COX-2, Ki-67, activated caspase-3, Akt, p-Akt, mitogen-activated protein kinase (MAPK), or p-MAPK. No significant differences in urinary survivin or BLCA-4 levels between treatment groups were observed. Genistein displayed a possible bimodal effect (more effective at the lower dose) on bladder cancer tissue EGFR phosphorylation that should be evaluated further, possibly in combination with other agents. Cancer Prev Res; 5(4); 621-30. (C) 2012 AACR. C1 [Gee, Jason R.; Kim, KyungMann; diSant'Agnese, Anthony; Kolesar, Jill; Harris, Linda; Faerber, Adrienne; Havighurst, Thomas; Bailey, Howard] Univ Wisconsin, Carbone Canc Ctr, Madison, WI 53792 USA. [Messing, Edward] Univ Rochester, Med Ctr, Rochester, NY 14642 USA. [Busby, J. Erik] Univ Alabama Birmingham, Birmingham, AL USA. [Hohl, Raymond] Univ Iowa, Iowa City, IA USA. [Young, Jay M.] S Orange Cty Med Res Ctr, Tustin, CA USA. [Saltzstein, Daniel R.] Urol San Antonio Res, San Antonio, TX USA. [Efros, Mitchell] AccuMed Res Associates LLC, Garden City, NY USA. [Getzenberg, Robert H.] Johns Hopkins Univ, Sch Med, Baltimore, MD USA. [Tangrea, Joseph; Parnes, Howard; House, Margaret] NCI, Canc Prevent Div, NIH, Bethesda, MD 20892 USA. [Wheeler, Marcia A.] Yale Univ, New Haven, CT USA. RP Bailey, H (reprint author), Univ Wisconsin, Carbone Canc Ctr, Box 6164 Clin Sci Ctr,600 Highland Ave, Madison, WI 53792 USA. EM hhb@medicine.wisc.edu FU NIH [N01 CN35153, P30 CA014520, 1UL1RR025011] FX The work was supported by NIH contract N01 CN35153 and grants P30 CA014520 and 1UL1RR025011. NR 55 TC 23 Z9 25 U1 1 U2 9 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1940-6207 J9 CANCER PREV RES JI Cancer Prev. Res. PD APR PY 2012 VL 5 IS 4 BP 621 EP 630 DI 10.1158/1940-6207.CAPR-11-0455 PG 10 WC Oncology SC Oncology GA 922TY UT WOS:000302572400017 PM 22293631 ER PT J AU Zaidi, MR De Fabo, EC Noonan, FP Merlino, G AF Zaidi, M. Raza De Fabo, Edward C. Noonan, Frances P. Merlino, Glenn TI Shedding Light on Melanocyte Pathobiology In Vivo SO CANCER RESEARCH LA English DT Review ID INTERFERON-GAMMA; ULTRAVIOLET-RADIATION; HLA-G; CANCER; EXPRESSION; MICE; MUTATIONS; MECHANISM; CTLA-4; MOUSE AB Cutaneous malignant melanoma is rapidly increasing in the developed world and continues to be a challenge in the clinic. Although extensive epidemiologic evidence points to solar UV as the major risk factor for melanoma, there is a significant gap in our knowledge about how this most ubiquitous environmental carcinogen interacts with the largest organ of the mammalian body (skin) at the microenvironmental and molecular level. We review some recent advances that have started to close this gap. Cancer Res; 72(7); 1591-5. (C) 2012 AACR. C1 [Zaidi, M. Raza; Merlino, Glenn] NCI, Lab Canc Biol & Genet, NIH, Bethesda, MD 20892 USA. [De Fabo, Edward C.; Noonan, Frances P.] George Washington Univ, Med Ctr, Lab Photobiol & Photoimmunol, Dept Microbiol Immunol & Trop Med, Washington, DC 20037 USA. RP Zaidi, MR (reprint author), NCI, Lab Canc Biol & Genet, NIH, 37 Convent Dr,Bldg 37,Room 5002, Bethesda, MD 20892 USA. EM zaidir@mail.nih.gov RI Zaidi, M. Raza/H-1386-2016 OI Zaidi, M. Raza/0000-0003-0480-3188 FU Intramural NIH HHS [Z99 CA999999] NR 29 TC 6 Z9 6 U1 0 U2 5 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 APR 1 PY 2012 VL 72 IS 7 BP 1591 EP 1595 DI 10.1158/0008-5472.CAN-11-2586 PG 5 WC Oncology SC Oncology GA 922MO UT WOS:000302551800001 PM 22422936 ER PT J AU Stevens, KN Fredericksen, Z Vachon, CM Wang, XS Margolin, S Lindblom, A Nevanlinna, H Greco, D Aittomaki, K Blomqvist, C Chang-Claude, J Vrieling, A Flesch-Janys, D Sinn, HP Wang-Gohrke, S Nickels, S Brauch, H Ko, YD Fischer, HP Schmutzler, RK Meindl, A Bartram, CR Schott, S Engel, C Godwin, AK Weaver, J Pathak, HB Sharma, P Brenner, H Muller, H Arndt, V Stegmaier, C Miron, P Yannoukakos, D Stavropoulou, A Fountzilas, G Gogas, HJ Swann, R Dwek, M Perkins, A Milne, RL Benitez, J Zamora, MP Perez, JIA Bojesen, SE Nielsen, SF Nordestgaard, BG Flyger, H Guenel, P Truong, T Menegaux, F Cordina-Duverger, E Burwinkel, B Marme, F Schneeweiss, A Sohn, C Sawyer, E Tomlinson, I Kerin, MJ Peto, J Johnson, N Fletcher, O Silva, ID Fasching, PA Beckmann, MW Hartmann, A Ekici, AB Lophatananon, A Muir, K Puttawibul, P Wiangnon, S Schmidt, MK Broeks, A Braaf, LM Rosenberg, EH Hopper, JL Apicella, C Park, DJ Southey, MC Swerdlow, AJ Ashworth, A Orr, N Schoemaker, MJ Anton-Culver, H Ziogas, A Bernstein, L Dur, CC Shen, CY Yu, JC Hsu, HM Hsiung, CN Hamann, U Dunnebier, T Rudiger, T Ulmer, HU Pharoah, PP Dunning, AM Humphreys, MK Wang, Q Cox, A Cross, SS Reed, MW Hall, P Czene, K Ambrosone, CB Ademuyiwa, F Hwang, H Eccles, DM Garcia-Closas, M Figueroa, JD Sherman, ME Lissowska, J Devilee, P Seynaeve, C Tollenaar, RAEM Hooning, MJ Andrulis, IL Knight, JA Glendon, G Mulligan, AM Winqvist, R Pylkas, K Jukkola-Vuorinen, A Grip, M John, EM Miron, A Alnaes, GG Kristensen, V Borresen-Dale, AL Giles, GG Baglietto, L McLean, CA Severi, G Kosel, ML Pankratz, VS Slager, S Olson, JE Radice, P Peterlongo, P Manoukian, S Barile, M Lambrechts, D Hatse, S Dieudonne, AS Christiaens, MR Chenevix-Trench, G Beesley, J Chen, XQ Mannermaa, A Kosma, VM Hartikainen, JM Soini, Y Easton, DF Couch, FJ AF Stevens, Kristen N. Fredericksen, Zachary Vachon, Celine M. Wang, Xianshu Margolin, Sara Lindblom, Annika Nevanlinna, Heli Greco, Dario Aittomaki, Kristiina Blomqvist, Carl Chang-Claude, Jenny Vrieling, Alina Flesch-Janys, Dieter Sinn, Hans-Peter Wang-Gohrke, Shan Nickels, Stefan Brauch, Hiltrud Ko, Yon-Dschun Fischer, Hans-Peter Schmutzler, Rita K. Meindl, Alfons Bartram, Claus R. Schott, Sarah Engel, Christoph Godwin, Andrew K. Weaver, JoEllen Pathak, Harsh B. Sharma, Priyanka Brenner, Hermann Mueller, Heiko Arndt, Volker Stegmaier, Christa Miron, Penelope Yannoukakos, Drakoulis Stavropoulou, Alexandra Fountzilas, George Gogas, Helen J. Swann, Ruth Dwek, Miriam Perkins, Annie Milne, Roger L. Benitez, Javier Pilar Zamora, Maria Arias Perez, Jose Ignacio Bojesen, Stig E. Nielsen, Sune F. Nordestgaard, Borge G. Flyger, Henrik Guenel, Pascal Therese Truong Menegaux, Florence Cordina-Duverger, Emilie Burwinkel, Barbara Marme, Frederick Schneeweiss, Andreas Sohn, Christof Sawyer, Elinor Tomlinson, Ian Kerin, Michael J. Peto, Julian Johnson, Nichola Fletcher, Olivia dos Santos Silva, Isabel Fasching, Peter A. Beckmann, Matthias W. Hartmann, Arndt Ekici, Arif B. Lophatananon, Artitaya Muir, Kenneth Puttawibul, Puttisak Wiangnon, Surapon Schmidt, Marjanka K. Broeks, Annegien Braaf, Linde M. Rosenberg, Efraim H. Hopper, John L. Apicella, Carmel Park, Daniel J. Southey, Melissa C. Swerdlow, Anthony J. Ashworth, Alan Orr, Nicholas Schoemaker, Minouk J. Anton-Culver, Hoda Ziogas, Argyrios Bernstein, Leslie Dur, Christina Clarke Shen, Chen-Yang Yu, Jyh-Cherng Hsu, Huan-Ming Hsiung, Chia-Ni Hamann, Ute Duennebier, Thomas Ruediger, Thomas Ulmer, Hans Ulrich Pharoah, Paul P. Dunning, Alison M. Humphreys, Manjeet K. Wang, Qin Cox, Angela Cross, Simon S. Reed, Malcom W. Hall, Per Czene, Kamila Ambrosone, Christine B. Ademuyiwa, Foluso Hwang, Helena Eccles, Diana M. Garcia-Closas, Montserrat Figueroa, Jonine D. Sherman, Mark E. Lissowska, Jolanta Devilee, Peter Seynaeve, Caroline Tollenaar, Rob A. E. M. Hooning, Maartje J. Andrulis, Irene L. Knight, Julia A. Glendon, Gord Mulligan, Anna Marie Winqvist, Robert Pylkas, Katri Jukkola-Vuorinen, Arja Grip, Mervi John, Esther M. Miron, Alexander Alnaes, Grethe Grenaker Kristensen, Vessela Borresen-Dale, Anne-Lise Giles, Graham G. Baglietto, Laura McLean, Catriona A. Severi, Gianluca Kosel, Matthew L. Pankratz, V. S. Slager, Susan Olson, Janet E. Radice, Paolo Peterlongo, Paolo Manoukian, Siranoush Barile, Monica Lambrechts, Diether Hatse, Sigrid Dieudonne, Anne-Sophie Christiaens, Marie-Rose Chenevix-Trench, Georgia Beesley, Jonathan Chen, Xiaoqing Mannermaa, Arto Kosma, Veli-Matti Hartikainen, Jaana M. Soini, Ylermi Easton, Douglas F. Couch, Fergus J. CA GENICA Network kConFab Investigators AOCS Grp TI 19p13.1 Is a Triple-Negative-Specific Breast Cancer Susceptibility Locus SO CANCER RESEARCH LA English DT Article ID GENOME-WIDE ASSOCIATION; COMMON VARIANTS; RISK-FACTORS; CONFER SUSCEPTIBILITY; 14Q24.1 RAD51L1; TUMOR SUBTYPES; BRCA1; POPULATION; CONSORTIUM; COMPLEX AB The 19p13.1 breast cancer susceptibility locus is a modifier of breast cancer risk in BRCA1 mutation carriers and is also associated with the risk of ovarian cancer. Here, we investigated 19p13.1 variation and risk of breast cancer subtypes, defined by estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor-2 (HER2) status, using 48,869 breast cancer cases and 49,787 controls from the Breast Cancer Association Consortium (BCAC). Variants from 19p13.1 were not associated with breast cancer overall or with ER-positive breast cancer but were significantly associated with ER-negative breast cancer risk [rs8170 OR, 1.10; 95% confidence interval (CI), 1.05-1.15; P = 3.49 x 10(-5)] and triple-negative (ER-, PR-, and HER2-negative) breast cancer (rs8170: OR, 1.22; 95% CI, 1.13-1.31; P = 2.22 x 10(-7)). However, rs8170 was no longer associated with ER-negative breast cancer risk when triple-negative cases were excluded (OR, 0.98; 95% CI, 0.89-1.07; P = 0.62). In addition, a combined analysis of triple-negative cases from BCAC and the Triple Negative Breast Cancer Consortium (TNBCC; N = 3,566) identified a genome-wide significant association between rs8170 and triple-negative breast cancer risk (OR, 1.25; 95% CI, 1.18-1.33; P = 3.31 x 10-(13)]. Thus, 19p13.1 is the first triple-negativespecific breast cancer risk locus and the first locus specific to a histologic subtype defined by ER, PR, and HER2 to be identified. These findings provide convincing evidence that genetic susceptibility to breast cancer varies by tumor subtype and that triple-negative tumors and other subtypes likely arise through distinct etiologic pathways. Cancer Res; 72(7); 1795-803. (C)2012 AACR. C1 [Wang, Xianshu; Couch, Fergus J.] Mayo Clin, Dept Lab Med & Pathol, Rochester, MN 55905 USA. [Stevens, Kristen N.; Fredericksen, Zachary; Vachon, Celine M.; Kosel, Matthew L.; Pankratz, V. S.; Slager, Susan; Olson, Janet E.] Mayo Clin, Dept Hlth Sci Res, Rochester, MN 55905 USA. [Margolin, Sara; Lindblom, Annika] Karolinska Univ Hosp, Dept Clin Genet, Stockholm, Sweden. [Hall, Per; Czene, Kamila] Karolinska Inst, Stockholm, Sweden. [Nevanlinna, Heli; Greco, Dario] Univ Helsinki, Dept Obstet & Gynecol, Helsinki, Finland. [Aittomaki, Kristiina] Univ Helsinki, Cent Hosp, Dept Clin Genet, Helsinki, Finland. [Blomqvist, Carl] Univ Helsinki, Dept Oncol, Helsinki, Finland. [Chang-Claude, Jenny; Vrieling, Alina; Nickels, Stefan] German Canc Res Ctr, Div Canc Epidemiol, Heidelberg, Germany. [Burwinkel, Barbara] German Canc Res Ctr, Mol Epidemiol Grp, Heidelberg, Germany. [Sinn, Hans-Peter] Univ Heidelberg Hosp, Dept Pathol, Heidelberg, Germany. [Schott, Sarah; Burwinkel, Barbara; Marme, Frederick; Schneeweiss, Andreas; Sohn, Christof] Univ Heidelberg Hosp, Dept Obstet & Gynecol, Heidelberg, Germany. [Bartram, Claus R.] Univ Heidelberg, Inst Human Genet, Heidelberg, Germany. [Marme, Frederick; Schneeweiss, Andreas] Univ Heidelberg, Natl Ctr Tumor Dis, Heidelberg, Germany. [Brenner, Hermann; Mueller, Heiko; Arndt, Volker] German Canc Res Ctr, Div Clin Epidemiol & Aging Res, D-6900 Heidelberg, Germany. [Flesch-Janys, Dieter] Univ Clin Hamburg Eppendorf, Inst Med Biometr & Epidemiol, Hamburg, Germany. [Wang-Gohrke, Shan] Univ Ulm, Dept Obstet & Gynecol, Ulm, Germany. [Brauch, Hiltrud] Dr Margarete Fischer Bosch Inst Clin Pharmacol, D-7000 Stuttgart, Germany. [Brauch, Hiltrud] Univ Tubingen, Tubingen, Germany. [Ko, Yon-Dschun] Johanniter Krankenhaus, Evangel Kliniken Bonn gGmbH, Dept Internal Med, Bonn, Germany. [Fischer, Hans-Peter] Univ Bonn, Inst Pathol, Fac Med, Bonn, Germany. [GENICA Network] German Social Accid Insurance IPA, Inst Prevent & Occupat Med, Bochum, Germany. [Schmutzler, Rita K.] Univ Hosp Cologne, CMMC, Dept Obstet & Gynaecol, Div Mol Gynecooncol, Cologne, Germany. [Meindl, Alfons] Tech Univ Munich, Klinikum Rechts Isar, Dept Obstet & Gynaecol, Div Tumor Genet, D-8000 Munich, Germany. [Engel, Christoph] Univ Leipzig, Inst Med Informat Stat & Epidemiol, Leipzig, Germany. [Godwin, Andrew K.; Pathak, Harsh B.] Univ Kansas, Med Ctr, Dept Pathol & Lab Med, Kansas City, KS 66103 USA. [Sharma, Priyanka] Univ Kansas, Med Ctr, Div Hematol & Oncol, Kansas City, KS 66103 USA. [Weaver, JoEllen] Fox Chase Canc Ctr, Philadelphia, PA 19111 USA. [Stegmaier, Christa] Saarland Canc Registry, Saarbrucken, Germany. [Miron, Penelope; Miron, Alexander] Dana Farber Canc Inst, Dept Canc Biol, Boston, MA 02115 USA. [Yannoukakos, Drakoulis; Stavropoulou, Alexandra] Natl Ctr Sci Res Demokritos, IRRP, Mol Diagnost Lab, Athens, Greece. [Gogas, Helen J.] Univ Athens, Sch Med, Dept Med 1, GR-11527 Athens, Greece. [Fountzilas, George] Aristotle Univ Thessaloniki, Sch Med, Papageorgiou Hosp, Dept Med Oncol, GR-54006 Thessaloniki, Greece. [Swann, Ruth; Dwek, Miriam; Perkins, Annie] Univ Westminster, Sch Life Sci, Against Breast Canc Res Unit, London W1R 8AL, England. [Sawyer, Elinor] Guys & St Thomas NHS Fdn Trust, Kings Coll London, Comprehens Biomed Res Ctr, NIHR, London, England. [Sawyer, Elinor] Kings Coll Hosp NHS Fdn Trust, London, England. [Peto, Julian] London Sch Hyg & Trop Med, Dept Noncommunicable Dis Epidemiol, London WC1, England. [dos Santos Silva, Isabel] London Sch Hyg & Trop Med, Fac Epidemiol & Populat Hlth, London WC1, England. [Johnson, Nichola; Fletcher, Olivia; Ashworth, Alan; Orr, Nicholas] Inst Canc Res, Breakthrough Breast Canc Res Ctr, London SW3 6JB, England. [Milne, Roger L.] Spanish Natl Canc Res Ctr CNIO, Genet & Mol Epidemiol Grp, Madrid, Spain. [Benitez, Javier] Spanish Natl Canc Res Ctr CNIO, Human Genet Grp, Madrid, Spain. [Pilar Zamora, Maria] Hosp Univ La Paz, Med Oncol Serv, Madrid, Spain. [Arias Perez, Jose Ignacio] Hosp Monte Naranco, Serv Cirugia Gen & Especialidades, Oviedo, Spain. [Bojesen, Stig E.; Nielsen, Sune F.; Nordestgaard, Borge G.] Copenhagen Univ Hosp, Herlev Hosp, Dept Clin Biochem, Herlev, Denmark. [Flyger, Henrik] Copenhagen Univ Hosp, Herlev Hosp, Dept Breast Surg, Herlev, Denmark. [Bojesen, Stig E.; Nielsen, Sune F.; Nordestgaard, Borge G.] Copenhagen Univ Hosp, Herlev Hosp, Copenhagen Gen Populat Study, Herlev, Denmark. [Guenel, Pascal; Therese Truong; Menegaux, Florence; Cordina-Duverger, Emilie] CESP Ctr Res Epidemiol & Populat Hlth, INSERM, U1018, Villejuif, France. 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[Wiangnon, Surapon] Khon Kaen Univ, Sch Med, Dept Pediat, Khon Kaen, Thailand. [Schmidt, Marjanka K.; Broeks, Annegien; Braaf, Linde M.; Rosenberg, Efraim H.] Netherlands Canc Inst, Amsterdam, Netherlands. [Hopper, John L.; Apicella, Carmel; Giles, Graham G.; Baglietto, Laura; Severi, Gianluca] Univ Melbourne, Ctr Mol Environm Genet & Analyt Epidemiol, Melbourne, Vic, Australia. [Park, Daniel J.; Southey, Melissa C.] Univ Melbourne, Dept Pathol, Melbourne, Vic, Australia. [Giles, Graham G.; Baglietto, Laura; Severi, Gianluca] Canc Council Victoria, Canc Epidemiol Ctr, Melbourne, Vic, Australia. [McLean, Catriona A.] Alfred Hosp, Melbourne, Vic, Australia. [kConFab Investigators] Peter MacCallum Canc Ctr, Melbourne, Vic, Australia. [Swerdlow, Anthony J.; Schoemaker, Minouk J.] Inst Canc Res, Epidemiol Sect, Sutton, Surrey, England. [Garcia-Closas, Montserrat] Inst Canc Res, Div Genet & Epidemiol, Sutton, Surrey, England. [Anton-Culver, Hoda; Ziogas, Argyrios] Univ Calif Irvine, Sch Med, Dept Epidemiol, Irvine, CA 92717 USA. [Bernstein, Leslie] City Hope Natl Med Ctr, Beckman Res Inst, Dept Populat Sci, Div Canc Etiol, Duarte, CA USA. [Dur, Christina Clarke; John, Esther M.] Canc Prevent Inst Calif, Dept Epidemiol, Fremont, CA USA. [Shen, Chen-Yang; Hsiung, Chia-Ni] Acad Sinica, Inst Biomed Sci, Taipei, Taiwan. [Yu, Jyh-Cherng; Hsu, Huan-Ming] Triserv Gen Hosp, Dept Surg, Taipei, Taiwan. [Ruediger, Thomas] Stadt Klinikum Karlsruhe, Inst Pathol, Karlsruhe, Germany. [Ulmer, Hans Ulrich; Easton, Douglas F.] Stadt Klinikum Karlsruhe, Womens Clin, Karlsruhe, Germany. [Pharoah, Paul P.; Dunning, Alison M.; Easton, Douglas F.] Univ Cambridge, Dept Oncol, Ctr Canc Genet Epidemiol, Cambridge, England. [Pharoah, Paul P.; Humphreys, Manjeet K.; Wang, Qin] Univ Cambridge, Dept Publ Hlth & Primary Care, Ctr Canc Genet Epidemiol, Cambridge, England. [Cox, Angela; Reed, Malcom W.] Univ Sheffield, Dept Oncol, Fac Med Dent & Hlth, Sheffield, S Yorkshire, England. [Cross, Simon S.] Univ Sheffield, Dept Neurosci, Fac Med Dent & Hlth, Sheffield, S Yorkshire, England. [Ambrosone, Christine B.] Roswell Pk Canc Inst, Dept Canc Prevent & Control, Buffalo, NY 14263 USA. [Ademuyiwa, Foluso] Roswell Pk Canc Inst, Dept Med, Buffalo, NY 14263 USA. [Hwang, Helena] Roswell Pk Canc Inst, Dept Pathol, Buffalo, NY 14263 USA. [Eccles, Diana M.] Univ Southampton, Fac Med, Southampton SO9 5NH, Hants, England. [Figueroa, Jonine D.; Sherman, Mark E.] NCI, Div Canc Epidemiol & Genet, Hormonal & Reprod Epidemiol Branch, NIH, Bethesda, MD 20892 USA. [Lissowska, Jolanta] M Sklodowska Curie Canc Ctr, Dept Canc Epidemiol & Prevent, Warsaw, Poland. [Lissowska, Jolanta] Inst Oncol, Warsaw, Poland. [Devilee, Peter] Leiden Univ, Dept Human Genet, Med Ctr, NL-2300 RA Leiden, Netherlands. [Devilee, Peter] Leiden Univ, Dept Pathol, Med Ctr, Leiden, Netherlands. [Tollenaar, Rob A. E. M.] Leiden Univ, Dept Surg Oncol, Med Ctr, Leiden, Netherlands. [Seynaeve, Caroline; Hooning, Maartje J.] Dr Daniel Den Hoed Canc Ctr, Erasmus Med Ctr, Dept Med Oncol, NL-3008 AE Rotterdam, Netherlands. [Andrulis, Irene L.] Univ Toronto, Dept Mol Genet, Toronto, ON, Canada. [Andrulis, Irene L.] Univ Toronto, Dept Lab Med & Pathobiol, Toronto, ON, Canada. [Knight, Julia A.] Univ Toronto, Dalla Lana Sch Publ Hlth, Prosserman Ctr Hlth Res, Toronto, ON, Canada. [Glendon, Gord] Princess Margaret Hosp, Toronto, ON M4X 1K9, Canada. [Mulligan, Anna Marie] St Michaels Hosp, Li Ka Shing Knowledge Inst, Dept Lab Med, Keenan Res Ctr, Toronto, ON M5B 1W8, Canada. [Winqvist, Robert; Pylkas, Katri] Univ Oulu, Bioctr Oulu, Inst Clin Med, Dept Clin Genet,Oulu Univ Hosp, Oulu, Finland. [Jukkola-Vuorinen, Arja] Univ Oulu, Dept Oncol, Oulu Univ Hosp, Oulu, Finland. [Grip, Mervi] Univ Oulu, Dept Surg, Oulu Univ Hosp, Oulu, Finland. [Alnaes, Grethe Grenaker; Kristensen, Vessela] Univ Oslo, Fac Med, Inst Clin Epidemiol & Mol Biol EpiGen, Oslo, Norway. [Alnaes, Grethe Grenaker; Kristensen, Vessela] Inst Canc Res, Dept Genet, Grp Canc Genome Variat, Oslo, Norway. [Borresen-Dale, Anne-Lise] Norwegian Radium Hosp, Inst Canc Res, Dept Genet, Oslo, Norway. [Radice, Paolo; Peterlongo, Paolo] Fdn IRCCS Ist Nazl, Dept Prevent & Predict Med, Unit Mol Bases Genet Risk & Genet Testing, Tumori INT, Milan, Italy. [Radice, Paolo; Peterlongo, Paolo] Fdn Ist FIRC Oncol Mol, IFOM, Milan, Italy. [Manoukian, Siranoush] Fdn IRCCS Ist Nazl Tumori INT, Dept Prevent & Predict Med, Unit Med Genet, Milan, Italy. [Barile, Monica] European Inst Oncol, Div Canc Prevent & Genet, Milan, Italy. [Lambrechts, Diether] VIB, Vesalius Res Ctr, Louvain, Belgium. [Lambrechts, Diether] Univ Louvain, Vesalius Res Ctr, Louvain, Belgium. [Hatse, Sigrid; Dieudonne, Anne-Sophie; Christiaens, Marie-Rose] Univ Hosp Gasthuisberg, Multidisciplinary Breast Ctr, B-3000 Louvain, Belgium. [Chenevix-Trench, Georgia; Beesley, Jonathan; Chen, Xiaoqing; AOCS Grp] Queensland Inst Med Res, Herston, Qld 4006, Australia. [Mannermaa, Arto; Kosma, Veli-Matti; Hartikainen, Jaana M.; Soini, Ylermi] Univ Eastern Finland, Dept Pathol, Inst Clin Med, Kuopio, Finland. [Mannermaa, Arto; Kosma, Veli-Matti; Hartikainen, Jaana M.; Soini, Ylermi] Kuopio Univ Hosp, Bioctr Kuopio, SF-70210 Kuopio, Finland. RP Couch, FJ (reprint author), Mayo Clin, Dept Lab Med & Pathol, Stabile 2-42,200 1st St SW, Rochester, MN 55905 USA. EM couch.fergus@mayo.edu RI manoukian, siranoush/E-7132-2017; Shen, CY/F-6271-2010; Verdrengh, Evelien/H-4571-2012; truong, therese/A-2837-2013; Kerin, Michael/D-6748-2013; Ekici, Arif/C-3971-2013; Andrulis, Irene/E-7267-2013; Radice, Paolo/O-3119-2013; Knight, Julia/A-6843-2012; Garcia-Closas, Montserrat /F-3871-2015; Hartikainen, Jaana/E-6256-2015; Vrieling, Alina/A-2725-2016; Bowtell, David/H-1007-2016; Brenner, Hermann/B-4627-2017 OI ADEMUYIWA, FOLUSO/0000-0002-6766-2258; Giles, Graham/0000-0003-4946-9099; Arndt, Volker/0000-0001-9320-8684; Schoemaker, Minouk/0000-0001-8403-2234; Greco, Dario/0000-0001-9195-9003; Czene, Kamila/0000-0002-3233-5695; Rosenberg, Efraim/0000-0002-3859-6941; Cross, Simon/0000-0003-2044-1754; Lissowska, Jolanta/0000-0003-2695-5799; Dunning, Alison Margaret/0000-0001-6651-7166; Nevanlinna, Heli/0000-0002-0916-2976; dos Santos Silva, Isabel/0000-0002-6596-8798; Cox, Angela/0000-0002-5138-1099; Yannoukakos, Drakoulis/0000-0001-7509-3510; Park, Daniel/0000-0002-6354-0931; manoukian, siranoush/0000-0002-6034-7562; Garcia-Closas, Montserrat /0000-0003-1033-2650; Bowtell, David/0000-0001-9089-7525; Brenner, Hermann/0000-0002-6129-1572 FU NIH [CA122340, RFA-CA-06-503, R01 CA77398, CA58860, CA92044]; SPORE [CA116201]; Komen Foundation for the Cure; Breast Cancer Research Foundation (BCRF); Cancer Research UK [C1287/A10118, C1287/A12014]; European Community [223175, HEALTH-F2-2009-223175]; European Union COST [BM0606]; Institute for Cancer Studies; ABCS; Dutch Cancer Society [NKI 2009-4363, NKI 2007-3839]; Dutch National Genomics Initiative; ACP: Breast Cancer Research Trust, UK; National Institute for Health Research (NIHR) Comprehensive Biomedical Research Centre; Guy's & St. Thomas' NHS Foundation; Oxford Biomedical Research Centre; ABCFS; NC-BCFR; OFBCR; National Cancer Institute; Cancer Care Ontario [U01 CA69467]; Northern California Cancer Center [U01 CA69417]; University of Melbourne [U01 CA69638]; ABCFS: National Health and Medical Research Council of Australia; New South Wales Cancer Council; Victorian Health Promotion Foundation (Australia); Victorian Breast Cancer Research Consortium; Asociacion Espanola Contra el Cancer; Fondo de Investigacion Sanitario [PI081583, PI081120]; The California Teachers Study; California Breast Cancer Act of 1993; Lon V Smith Foundation [LVS39420]; California Breast Cancer Research Fund [97-10500]; UCIBCS; ESTHER; Baden Wurttemberg Ministry of Science; German Cancer Aid (Deutsche Krebshilfe) FX This work was supported by the NIH grant CA122340, a Specialized Program of Research Excellence (SPORE) in Breast Cancer (CA116201), the Komen Foundation for the Cure and the Breast Cancer Research Foundation (BCRF); the BCAC is funded by Cancer Research UK (C1287/A10118 and C1287/A12014), by the European Community's Seventh Framework Programme under grant agreement no. 223175 (HEALTH-F2-2009-223175; COGS), and by the European Union COST programme (BM0606). D.F. Easton is a Principal Research Fellow of Cancer Research UK; SBCS: Breast Cancer Campaign (2004 Nov 49 to A. Cox) and Yorkshire Cancer Research Core Funding (Institute for Cancer Studies); ABCS: Dutch Cancer Society grant (NKI 2009-4363 and NKI 2007-3839 to M.K. Schmidt) and the Dutch National Genomics Initiative; ACP: Breast Cancer Research Trust, UK. E. Sawyer is funded by National Institute for Health Research (NIHR) Comprehensive Biomedical Research Centre, Guy's & St. Thomas' NHS Foundation Trust in partnership with King's College London. I. Tomlinson is funded by the Oxford Biomedical Research Centre; ABCFS, NC-BCFR and OFBCR: National Cancer Institute, NIH under RFA-CA-06-503, and through cooperative agreements with members of the Breast Cancer Family Registry (BCFR) and Principal Investigators, including Cancer Care Ontario (U01 CA69467), Northern California Cancer Center (U01 CA69417), University of Melbourne (U01 CA69638); ABCFS: National Health and Medical Research Council of Australia, the New South Wales Cancer Council, the Victorian Health Promotion Foundation (Australia), and the Victorian Breast Cancer Research Consortium. J.L. Hopper is a National Health and Medical Research Council (NHMRC) Australia Fellow and a Victorian Breast Cancer Research Consortium Group Leader. M.C. Southey is an NHMRC Senior Research Fellow and a Victorian Breast Cancer Research Consortium Group Leader; CNIO-BCS: Genome Spain Foundation, the Red Tematica de Investigacion Cooperativa en Cancer and grants from the Asociacion Espanola Contra el Cancer and the Fondo de Investigacion Sanitario (PI081583 and PI081120); The California Teachers Study: California Breast Cancer Act of 1993, NIH (R01 CA77398), the Lon V Smith Foundation [LVS39420]), and the California Breast Cancer Research Fund (contract 97-10500); UCIBCS: NIH (CA58860 and CA92044) and the Lon V Smith Foundation (LVS39420); ESTHER: Baden Wurttemberg Ministry of Science, Research and Arts, and the VERDI study supported by a grant from the German Cancer Aid (Deutsche Krebshilfe); GENICA: Federal Ministry of Education and Research (BMBF) Germany (01KW9975/5, 01KW9976/8, 01KW9977/0 and 01KW0114), the Robert Bosch Foundation, Stuttgart, Deutsches Krebsforschungszentrum (DKFZ) Heidelberg, Institute for Prevention and Occupational Medicine of the German Social Accident Insurance (IPA), Bochum, and the Department of Internal Medicine, Evangelische Kliniken Bonn gGmbH, Johanniter Krankenhaus, Bonn, Germany: KBCP: Finnish Cancer Society, the Academy of Finland (grant number 127220), the special Government Funding (EVO) of Kuopio University Hospital (grant number 5654113 and 5501) and by the strategic funding of the University of Eastern Finland; OBCS: Finnish Cancer Foundation, the Academy of Finland, the University of Oulu, the Oulu University Hospital and Biocenter Oulu; RPCI: P30 grant to RPCI (CA016056-32); The Breakthrough Generations Study: Breakthrough Breast Cancer and the Institute of Cancer Research (ICR).; ICR acknowledges NHS funding to the NIHR Biomedical Research Centre; PBCS: Intramural Research Funds of the National Cancer Institute, Bethesda, MD; HEBCS: Helsinki University Central Hospital Research Fund, Academy of Finland (132473), the Finnish Cancer Society, and the Sigrid Juselius Foundation; MARIE: Deutsche Krebshilfe e.V., grant number 70-2892-BR I, the Hamburg Cancer Society, the German Cancer Research Center (DKFZ), and the Federal Ministry of Education and Research (BMBF) Germany grant 01KH0402; GESBC: Deutsche Krebshilfe e. V. (70492) and the state of Baden-Wurttemberg through the Medical Faculty of the University of Ulm (P.685); BSUCH: Dietmar Hopp Foundation, the German Cancer Research Center, DKFZ, and the Helmholtz association; GC-HBOC: Deutsche Krebshilfe (107054), the Center of Molecular Medicine, Cologne, the German Cancer Research Center, DKFZ, and the Helmholtz society; BBCS: Cancer Research UK, Breakthrough Breast Cancer and the National Cancer Research Network (NCRN); kConFab: National Breast Cancer Foundation, the National Health and Medical Research Council (NHMRC) and by the Queensland Cancer Fund, the Cancer Councils of New South Wales, Victoria, Tasmania, and South Australia, the Cancer Foundation of Western Australia, and Cancer Australia #628333; LMBC: 'Stichting tegen Kanker' (232-2008 and 196-2010); MCCS: Australian National Health and Medical Research Council (grants #209057, 251533, 396414, and 504711), Cancer Council Victoria, and VicHealth; ORIGO: Dutch Cancer Society; SEARCH: Cancer Research UK (C8197/A10123, C8197/A10123, and C490/A10124). A.M. Dunning was supported by Cancer Research UK grant (C8197/A10865) and by the Joseph Mitchell Fund; FCCC: NIH (U01 CA69631, 5U01 CA113916 to A.K. Godwin), the Eileen Stein Jacoby Fund, The University of Kansas Cancer Center, and the Kansas Bioscience Authority Eminent Scholar Program. A.K. Godwin is the Chancellors Distinguished Chair in Biomedical Sciences endowed Professor. NR 24 TC 42 Z9 43 U1 1 U2 12 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 APR 1 PY 2012 VL 72 IS 7 BP 1795 EP 1803 DI 10.1158/0008-5472.CAN-11-3364 PG 9 WC Oncology SC Oncology GA 922MO UT WOS:000302551800022 PM 22331459 ER PT J AU Chen, KG Sikic, BI AF Chen, Kevin G. Sikic, Branimir I. TI Molecular Pathways: Regulation and Therapeutic Implications of Multidrug Resistance SO CLINICAL CANCER RESEARCH LA English DT Article ID ACUTE MYELOID-LEUKEMIA; PHASE-I TRIAL; HUMAN MDR1 GENE; P-GLYCOPROTEIN EXPRESSION; BREAST-CANCER CELLS; TRANSCRIPTIONAL REGULATION; LYMPHOCYTIC-LEUKEMIA; EPIGENETIC CHANGES; DRUG-RESISTANCE; PROMOTER REGION AB Multidrug transporters constitute major mechanisms of MDR in human cancers. The ABCB1 (MDR1) gene encodes a well-characterized transmembrane transporter, termed P-glycoprotein (P-gp), which is expressed in many normal human tissues and cancers. P-gp plays a major role in the distribution and excretion of drugs and is involved in intrinsic and acquired drug resistance of cancers. The regulation of ABCB1 expression is complex and has not been well studied in a clinical setting. In this review, we elucidate molecular signaling and epigenetic interactions that govern ABCB1 expression and the development of MDR in cancer. We focus on acquired expression of ABCB1 that is associated with genomic instability of cancer cells, including mutational events that alter chromatin structures, gene rearrangements, and mutations in tumor suppressor proteins (e. g., mutant p53), which guard the integrity of genome. In addition, epigenetic modifications of the ABCB1 proximal and far upstream promoters by either demethylation of DNA or acetylation of histone H3 play a pivotal role in inducing ABCB1 expression. We describe a molecular network that coordinates genetic and epigenetic events leading to the activation of ABCB1. These mechanistic insights provide additional translational targets and potential strategies to deal with clinical MDR. Clin Cancer Res; 18(7); 1863-9. (C) 2012 AACR. C1 [Chen, Kevin G.; Sikic, Branimir I.] Stanford Univ, Dept Med, Div Oncol, Sch Med, Stanford, CA 94305 USA. [Chen, Kevin G.] Natl Inst Neurol Disorders & Stroke, NIH Stem Cell Unit, NIH, Bethesda, MD USA. RP Sikic, BI (reprint author), Stanford Univ, Dept Med, Div Oncol, Sch Med, CCSR 1105, Stanford, CA 94305 USA. EM brandy@stanford.edu RI Chen, Kevin/D-6769-2011 OI Chen, Kevin/0000-0003-2983-6330 FU National Cancer Institute [CA09302]; NIH [R01 CA52168, R01 CA92474]; General Clinical Research Center, Stanford University [M01 RR0070] FX This work was supported by National Cancer Institute grant CA09302 (K.G. Chen), NIH grants R01 CA52168 and R01 CA92474 (B. I. Sikic), and M01 RR0070 (General Clinical Research Center, Stanford University). NR 68 TC 74 Z9 83 U1 3 U2 22 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 APR 1 PY 2012 VL 18 IS 7 BP 1863 EP 1869 DI 10.1158/1078-0432.CCR-11-1590 PG 7 WC Oncology SC Oncology GA 922LX UT WOS:000302549900008 PM 22344233 ER PT J AU Lockwood, WW Thu, KL Lin, L Pikor, LA Chari, R Lam, WL Beer, DG AF Lockwood, William W. Thu, Kelsie L. Lin, Lin Pikor, Larissa A. Chari, Raj Lam, Wan L. Beer, David G. TI Integrative Genomics Identified RFC3 As an Amplified Candidate Oncogene in Esophageal Adenocarcinoma SO CLINICAL CANCER RESEARCH LA English DT Article ID REPLICATION-FACTOR-C; NUCLEOTIDE POLYMORPHISM ARRAYS; SQUAMOUS-CELL CARCINOMA; COPY NUMBER ALTERATIONS; BARRETTS-ESOPHAGUS; CHROMOSOMAL-ABERRATIONS; GASTRIC CARDIA; N-MYC; HYBRIDIZATION; CANCER AB Purpose: Esophageal adenocarcinoma (EAC) is a lethal malignancy that can develop from the premalignant condition, Barrett's esophagus (BE). Currently, there are no validated simple methods to predict which patients will progress to EAC. A better understanding of the genetic mechanisms driving EAC tumorigenesis is needed to identify new therapeutic targets and develop biomarkers capable of identifying high-risk patients that would benefit from aggressive neoadjuvant therapy. We employed an integrative genomics approach to identify novel genes involved inEAC biology that may serve as useful clinical markers. Experimental Design: Whole genome tiling-path array comparative genomic hybridization was used to identify significant regions of copy number alteration in 20 EACs and 10 matching BE tissues. Copy number and gene expression data were integrated to identify candidate oncogenes within regions of amplification and multiple additional sample cohorts were assessed to validate candidate genes. Results: We identified RFC3 as a novel, candidate oncogene activated by amplification in approximately 25% of EAC samples. RFC3 was also amplified in BE from a patient whose EAC harbored amplification and was differentially expressed between nonmalignant and EAC tissues. Copy number gains were detected in other cancer types and RFC3 knockdown inhibited proliferation and anchorage-independent growth of cancer cells with increased copy number but had little effect on those without. Moreover, high RFC3 expression was associated with poor patient outcome in multiple cancer types. Conclusions: RFC3 is a candidate oncogene amplified in EAC. RFC3 DNA amplification is also prevalent in other epithelial cancer types and RFC3 expression could serve as a prognostic marker. Clin Cancer Res; 18(7); 1936-46. (C) 2012 AACR. C1 [Lockwood, William W.; Thu, Kelsie L.; Pikor, Larissa A.; Chari, Raj; Lam, Wan L.] British Columbia Canc Res Ctr, Vancouver, BC V5Z 1L3, Canada. [Lin, Lin; Beer, David G.] Univ Michigan, Dept Surg, Ann Arbor, MI 48109 USA. RP Lockwood, WW (reprint author), NHGRI, Canc Genet Branch, NIH, 50 South Dr, Bethesda, MD 20892 USA. EM william.lockwood@nih.gov FU Canadian Institutes of Health Research; Canadian Cancer Society FX This work was supported by the Canadian Institutes of Health Research (W. L. Lam), Canadian Cancer Society (W. L. Lam), and Canadian Institutes of Health Research Vanier Canada Graduate Scholarships (K. L. Thu and L. A. Pikor), and CIHR Jean-Francois Saint Denis Fellowship in Cancer Research (W. W. Lockwood). NR 47 TC 14 Z9 14 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 J9 CLIN CANCER RES JI Clin. Cancer Res. PD APR 1 PY 2012 VL 18 IS 7 BP 1936 EP 1946 DI 10.1158/1078-0432.CCR-11-1431 PG 11 WC Oncology SC Oncology GA 922LX UT WOS:000302549900015 PM 22328562 ER PT J AU Chapman, CM Sun, XM Roschewski, M Aue, G Farooqui, M Stennett, L Gibellini, F Arthur, D Perez-Galan, P Wiestner, A AF Chapman, Colby M. Sun, Xiameng Roschewski, Mark Aue, Georg Farooqui, Mohamed Stennett, Lawrence Gibellini, Federica Arthur, Diane Perez-Galan, Patricia Wiestner, Adrian TI ON 01910.Na Is Selectively Cytotoxic for Chronic Lymphocytic Leukemia Cells through a Dual Mechanism of Action Involving PI3K/AKT Inhibition and Induction of Oxidative Stress SO CLINICAL CANCER RESEARCH LA English DT Article ID SMALL-MOLECULE INHIBITOR; CLL-B-CELLS; INDUCED APOPTOSIS; THERAPEUTIC APPROACH; MEDIATED MECHANISM; LYMPHOMA-CELLS; CANCER-CELLS; RECEPTOR; ROS; PROLIFERATION AB Purpose: Chronic lymphocytic leukemia (CLL), a malignancy of mature B cells, is incurable with chemotherapy. Signals from the microenvironment support leukemic cell survival and proliferation and may confer chemotherapy resistance. ON 01910.Na (Rigosertib), a multikinase phosphoinositide 3-kinase (PI3K) inhibitor, is entering phase III trials for myelodysplastic syndrome. Our aim was to analyze the efficacy of ON 01910.Na against CLL cells in vitro and investigate the molecular effects of this drug on tumor biology. Experimental Design: Cytotoxicity of ON 01910.Na against CLL cells from 34 patients was determined in vitro with flow cytometry of cells stained with Annexin V and CD19. Global gene expression profiling on Affymetrix microarrays, flow cytometry, Western blotting, and cocultures with stroma cells were used to delineate ON 01910.Na mechanism of action. Results: ON 01910.Na induced apoptosis in CLL B cells without significant toxicity against T cells or normal B cells. ON 01910.Na was equally active against leukemic cells associated with a more aggressive disease course [immunoglobulin heavy-chain variable region unmutated, adverse cytogenetics] than against cells without these features. Gene expression profiling revealed two main mechanisms of action: PI3K/AKT inhibition and induction of ROS that resulted in an oxidative stress response through activating protein 1 (AP-1), c-jun-NH2-terminal kinase, and ATF3 culminating in the upregulation of NOXA. ROS scavengers and shRNA mediated knockdown of ATF3- and NOXA-protected cells from drug-induced apoptosis. ON 01910.Na also abrogated the prosurvival effect of follicular dendritic cells on CLL cells and reduced SDF-1-induced migration of leukemic cells. Conclusions: These data support the clinical development of ON 01910.Na in CLL. Clin Cancer Res; 18(7); 1979-91. (C) 2012 AACR. C1 [Chapman, Colby M.; Sun, Xiameng; Roschewski, Mark; Aue, Georg; Farooqui, Mohamed; Stennett, Lawrence; Gibellini, Federica; Wiestner, Adrian] NHLBI, Hematol Branch, NIH, Bethesda, MD 20892 USA. [Arthur, Diane] NCI, Pathol Lab, Ctr Canc Res, Bethesda, MD 20892 USA. [Perez-Galan, Patricia] IDIBAPS, Ctr Esther Koplowitz, Dept Hematooncol, Barcelona 08036, Spain. RP Wiestner, A (reprint author), NHLBI, Hematol Branch, NIH, Bldg 10,CRC 3-5140,10 Ctr Dr, Bethesda, MD 20892 USA. EM pperez@clinic.ub.es; wiestnea@nhlbi.nih.gov OI Roschewski, Mark/0000-0003-0278-2635 FU National, Heart, Lung and Blood Institute; National Cancer Institute, NIH; Spanish Ministry of Science and Innovation [RYC2009-05134] FX This work was supported by the Intramural Research Program of the National, Heart, Lung and Blood Institute and the National Cancer Institute, NIH and the Spanish Ministry of Science and Innovation (RYC2009-05134). NR 50 TC 32 Z9 32 U1 0 U2 9 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1078-0432 J9 CLIN CANCER RES JI Clin. Cancer Res. PD APR 1 PY 2012 VL 18 IS 7 BP 1979 EP 1991 DI 10.1158/1078-0432.CCR-11-2113 PG 13 WC Oncology SC Oncology GA 922LX UT WOS:000302549900019 PM 22351695 ER PT J AU Prieto, PA Yang, JC Sherry, RM Hughes, MS Kammula, US White, DE Levy, CL Rosenberg, SA Phan, GQ AF Prieto, Peter A. Yang, James C. Sherry, Richard M. Hughes, Marybeth S. Kammula, Udai S. White, Donald E. Levy, Catherine L. Rosenberg, Steven A. Phan, Giao Q. TI CTLA-4 Blockade with Ipilimumab: Long-term Follow-up of 177 Patients with Metastatic Melanoma SO CLINICAL CANCER RESEARCH LA English DT Article ID LYMPHOCYTE-ASSOCIATED ANTIGEN-4; HIGH-DOSE INTERLEUKIN-2; REGULATORY T-CELLS; RECOMBINANT INTERLEUKIN-2; COMPLETE RESPONSES; CANCER REGRESSION; TUMOR-REGRESSION; PHASE-I/II; AUTOIMMUNITY; EFFICACY AB Purpose: Treatment with ipilimumab can cause objective tumor responses in patients with metastatic melanoma. We have treated 177 evaluable patients in three clinical trials and have long-term follow-up to evaluate the durability of responses. Experimental Design: Patients with metastatic melanoma were treated in three trials from 2002 to 2005. In protocol 1, 56 patients received ipilimumab with gp100 peptides. In protocol 2, 36 patients received ipilimumab with interleukin-2. In protocol 3, 85 patients received ipilimumab with intrapatient dose-escalation and were randomized to receive gp100 peptides. We have analyzed their long-term follow-up and survival data. Results: With median follow-up for protocols 1, 2, and 3 being 92, 84, and 71 months, median survival was 14, 16, and 13 months with 5-year survival rates being 13%, 25%, and 23%, respectively. Patients in protocol 2 had a 17% complete response (CR) rate, compared with 7% in protocol 1 and 6% in protocol 3. These CR rates are higher than previously reported for the same trials because some patients who eventually became complete responders had continual tumor regression months to years after therapy. All but one of the 15 complete responders are ongoing at 54+ to 99+ months. Conclusions: This report provides the longest follow-up of patients with melanoma treated with ipilimumab and shows that ipilimumab can induce durable, potentially curative tumor regression in a small percentage of patients with metastatic melanoma. The combination of ipilimumab and interleukin-2 seems to have an increased CR rate, but this needs to be tested in a randomized trial. Clin Cancer Res; 18(7); 2039-47. (C) 2012 AACR. C1 [Prieto, Peter A.; Yang, James C.; Sherry, Richard M.; Hughes, Marybeth S.; Kammula, Udai S.; White, Donald E.; Levy, Catherine L.; Rosenberg, Steven A.; Phan, Giao Q.] NCI, Surg Branch, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. RP Phan, GQ (reprint author), NCI, Surg Branch, Ctr Canc Res, NIH, Bldg 10 CRC,Room 3-5760,10 Ctr Dr, Bethesda, MD 20892 USA. EM Giao.Phan@nih.gov FU NIH FX This work was supported by NIH. NR 35 TC 231 Z9 237 U1 2 U2 15 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 APR 1 PY 2012 VL 18 IS 7 BP 2039 EP 2047 DI 10.1158/1078-0432.CCR-11-1823 PG 9 WC Oncology SC Oncology GA 922LX UT WOS:000302549900025 PM 22271879 ER PT J AU Peer, CJ Sissung, TM Kim, A Jain, L Woo, S Gardner, ER Kirkland, CT Troutman, SM English, BC Richardson, ED Federspiel, J Venzon, D Dahut, W Kohn, E Kummar, S Yarchoan, R Giaccone, G Widemann, B Figg, WD AF Peer, Cody J. Sissung, Tristan M. Kim, AeRang Jain, Lokesh Woo, Sukyung Gardner, Erin R. Kirkland, C. Tyler Troutman, Sarah M. English, Bevin C. Richardson, Emily D. Federspiel, Joel Venzon, David Dahut, William Kohn, Elise Kummar, Shivaani Yarchoan, Robert Giaccone, Giuseppe Widemann, Brigitte Figg, William D. TI Sorafenib Is an Inhibitor of UGT1A1 but Is Metabolized by UGT1A9: Implications of Genetic Variants on Pharmacokinetics and Hyperbilirubinemia SO CLINICAL CANCER RESEARCH LA English DT Article ID CRIGLER-NAJJAR; PHASE-I; UDP-GLUCURONOSYLTRANSFERASE; ANTITUMOR-ACTIVITY; PROSTATE-CANCER; GLUCURONIDATION; BILIRUBIN; THERAPY; TRIAL; BEVACIZUMAB AB Purpose: Several case reports suggest sorafenib exposure and sorafenib-induced hyperbilirubinemia may be related to a (TA)(5/6/7) repeat polymorphism in UGT1A1*28 (UGT, uridine glucuronosyl transferase). We hypothesized that sorafenib inhibits UGT1A1 and individuals carrying UGT1A1*28 and/or UGT1A9 variants experience greater sorafenib exposure and greater increase in sorafenib-induced plasma bilirubin concentration. Experimental Design: Inhibition of UGT1A1-mediated bilirubin glucuronidation by sorafenib was assessed in vitro. UGT1A1*28 and UGT1A9*3 genotypes were ascertained with fragment analysis or direct sequencing in 120 cancer patients receiving sorafenib on five different clinical trials. Total bilirubin measurements were collected in prostate cancer patients before receiving sorafenib (n=41) and 19 to 30 days following treatment and were compared with UGT1A1*28 genotype. Results: Sorafenib exhibited mixed-mode inhibition of UGT1A1-mediated bilirubin glucuronidation (IC50 = 18 mu mol/L; K-i = 11.7 mu mol/L) in vitro. Five patients carrying UGT1A1*28/*28 (n = 4) or UGT1A9*3/*3 (n 1) genotypes had first dose, dose-normalized areas under the sorafenib plasma concentration versus time curve (AUC) that were in the 93rd percentile, whereas three patients carrying UGT1A1*28/*28 had AUCs in the bottom quartile of all genotyped patients. The Drug Metabolizing Enzymes and Transporters genotyping platform was applied to DNA obtained from six patients, which revealed the ABCC2-24C>T genotype cosegregated with sorafenib AUC phenotype. Sorafenib exposure was related to plasma bilirubin increases in patients carrying 1 or 2 copies of UGT1A1*28 alleles (n = 12 and n = 5; R-2 = 0.38 and R-2 = 0.77; P = 0.032 and P = 0.051, respectively). UGT1A1*28 carriers showed two distinct phenotypes that could be explained by ABCC2-24C>T genotype and are more likely to experience plasma bilirubin increases following sorafenib if they had high sorafenib exposure. Conclusions: This pilot study indicates that genotype status of UGT1A1, UGT1A9, and ABCC2 and serum bilirubin concentration increases reflect abnormally highAUCin patients treated with sorafenib. Clin Cancer Res; 18(7); 2099-107. (C) 2012 AACR. C1 [Figg, William D.] NCI, Med Oncol Branch, CCR, NIH,Clin Pharmacol Program, Bethesda, MD 20892 USA. [Kim, AeRang; Widemann, Brigitte] NCI, Pharmacol & Expt Therapeut Sect, Bethesda, MD 20892 USA. [Kirkland, C. Tyler; Troutman, Sarah M.; English, Bevin C.; Richardson, Emily D.; Figg, William D.] NCI, Mol Pharmacol Sect, Bethesda, MD 20892 USA. [Venzon, David] NCI, Biostat & Data Management Branch, Bethesda, MD 20892 USA. [Dahut, William; Kohn, Elise; Kummar, Shivaani; Giaccone, Giuseppe] NCI, Med Oncol Branch, Bethesda, MD 20892 USA. [Yarchoan, Robert] NCI, HIV AIDS Malignancy Branch, Bethesda, MD 20892 USA. RP Figg, WD (reprint author), NCI, Med Oncol Branch, CCR, NIH,Clin Pharmacol Program, 9000 Rockville Pike,Bldg 10,Room 5A01, Bethesda, MD 20892 USA. EM wf13e@nih.gov RI Figg Sr, William/M-2411-2016; Giaccone, Giuseppe/E-8297-2017 OI Giaccone, Giuseppe/0000-0002-5023-7562 NR 32 TC 56 Z9 58 U1 2 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 APR 1 PY 2012 VL 18 IS 7 BP 2099 EP 2107 DI 10.1158/1078-0432.CCR-11-2484 PG 9 WC Oncology SC Oncology GA 922LX UT WOS:000302549900031 PM 22307138 ER PT J AU Narva, AS AF Narva, Andrew S. TI Decision Support and CKD: Not There Yet SO CLINICAL JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Editorial Material ID PRIMARY-CARE C1 NIDDKD, Natl Kidney Dis Educ Program, Div Kidney Urol & Hematol Dis, NIH, Bethesda, MD 20892 USA. RP Narva, AS (reprint author), NIDDKD, Natl Kidney Dis Educ Program, Div Kidney Urol & Hematol Dis, NIH, 2 Democracy Pl,Room 645,6707 Democracy Blvd, Bethesda, MD 20892 USA. EM narvaa@nidclk.nih.gov NR 9 TC 5 Z9 5 U1 0 U2 0 PU AMER SOC NEPHROLOGY PI WASHINGTON PA 1725 I ST, NW STE 510, WASHINGTON, DC 20006 USA SN 1555-9041 J9 CLIN J AM SOC NEPHRO JI Clin. J. Am. Soc. Nephrol. PD APR PY 2012 VL 7 IS 4 BP 525 EP 526 DI 10.2215/CJN.02140212 PG 2 WC Urology & Nephrology SC Urology & Nephrology GA 918WK UT WOS:000302281900001 PM 22422537 ER EF