FN Thomson Reuters Web of Science™ VR 1.0 PT J AU Beach, JR Billington, N Remmert, K Barzik, M Heissler, SM Shao, L Li, D Friedman, TB Betzig, E Sellers, JR Hammer, JA AF Beach, J. R. Billington, N. Remmert, K. Barzik, M. Heissler, S. M. Shao, L. Li, D. Friedman, T. B. Betzig, E. Sellers, J. R. Hammer, J. A. TI Myosin 18A Co-assembles with Myosin II to Drive the Functional Diversity of Myosin II Bipolar Filaments. SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract CT ASCB/IFCB Meeting CY DEC 06-10, 2014 CL Philadelphia, PA SP Amer Soc Cell Biol, Int Federat Cell Biol C1 [Beach, J. R.; Remmert, K.; Hammer, J. A.] NHLBI, LCB, NIH, Bethesda, MD 20892 USA. [Billington, N.; Heissler, S. M.] NHLBI, NIH, Bethesda, MD 20892 USA. [Barzik, M.] NIDCD, NIH, Bethesda, MD USA. [Shao, L.; Li, D.; Betzig, E.] HHMI, Ashburn, VA USA. [Friedman, T. B.] NIDCD, NIH, Rockville, MD USA. [Sellers, J. R.] NHLBI, LMP, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 EI 1939-4586 J9 MOL BIOL CELL JI Mol. Biol. Cell PD DEC PY 2014 VL 25 MA P107 PG 2 WC Cell Biology SC Cell Biology GA CE8LP UT WOS:000352094100108 ER PT J AU Bruun, K Beach, JR Murugesan, S Remmert, K Hammer, JA AF Bruun, K. Beach, J. R. Murugesan, S. Remmert, K. Hammer, J. A. TI Investigating the Role of Myosin 18A in Golgi Morphology. SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract CT ASCB/IFCB Meeting CY DEC 06-10, 2014 CL Philadelphia, PA SP Amer Soc Cell Biol, Int Federat Cell Biol C1 [Bruun, K.] St Josephs Univ, Dept Biol, Philadelphia, PA 19131 USA. [Beach, J. R.] NHLBI, CBPC, NIH, Bethesda, MD 20892 USA. [Murugesan, S.] NHLBI, NIH, Bethesda, MD 20892 USA. [Remmert, K.; Hammer, J. A.] NHLBI, LCB, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 2 U2 2 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 EI 1939-4586 J9 MOL BIOL CELL JI Mol. Biol. Cell PD DEC PY 2014 VL 25 MA P2096 PG 2 WC Cell Biology SC Cell Biology GA CE8LP UT WOS:000352094105125 ER PT J AU Case, L Baird, M Shtengel, G Campbell, S Hess, H Davidson, MW Waterman, C AF Case, L. Baird, M. Shtengel, G. Campbell, S. Hess, H. Davidson, M. W. Waterman, C. TI iPALM and FRET reveal the mechanism of vinculin activation and nano-scale spatial organization in focal adhesions SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract CT ASCB/IFCB Meeting CY DEC 06-10, 2014 CL Philadelphia, PA SP Amer Soc Cell Biol, Int Federat Cell Biol C1 [Case, L.] NHLBI, Cell Biol & Physiol Ctr, NIH, Bethesda, MD 20892 USA. [Baird, M.] Florida State Univ, Tallahassee, FL 32306 USA. [Shtengel, G.; Hess, H.] HHMI, Janelia Farm, Ashburn, VA USA. [Campbell, S.] UNC, Biochem & Biophys, Chapel Hill, NC USA. [Davidson, M. W.] Florida State Univ, Natl High Magnet Field Lab, Tallahassee, FL 32306 USA. [Davidson, M. W.] Florida State Univ, Dept Biol Sci, Tallahassee, FL 32306 USA. [Waterman, C.] Natl Inst Hlth, Natl Heart Lung & Blood Inst, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 2 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 EI 1939-4586 J9 MOL BIOL CELL JI Mol. Biol. Cell PD DEC PY 2014 VL 25 MA P1463 PG 1 WC Cell Biology SC Cell Biology GA CE8LP UT WOS:000352094103314 ER PT J AU Cekan, P Ryu, S Hasegawa, K Lee, J Kalab, P AF Cekan, P. Ryu, S. Hasegawa, K. Lee, J. Kalab, P. TI Ran GTPase activates DNA damage response and cell cycle resumption, driving the evasion of cell senescence in normal and cancer cells SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract CT ASCB/IFCB Meeting CY DEC 06-10, 2014 CL Philadelphia, PA SP Amer Soc Cell Biol, Int Federat Cell Biol C1 [Cekan, P.; Ryu, S.; Hasegawa, K.; Lee, J.; Kalab, P.] NCI, NIH, Bethesda, MD 20892 USA. [Ryu, S.] Samsung Adv Inst Technol, Well Aging Res Ctr, Osan, South Korea. [Hasegawa, K.] Amherst Coll, Biochem Biophys, Amherst, MA 01002 USA. NR 0 TC 0 Z9 0 U1 1 U2 2 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 EI 1939-4586 J9 MOL BIOL CELL JI Mol. Biol. Cell PD DEC PY 2014 VL 25 MA P219 PG 1 WC Cell Biology SC Cell Biology GA CE8LP UT WOS:000352094100220 ER PT J AU Cervantes, CBL Tokuhiro, K Zhang, Y Conti, M Bae, DH Daniels, M Dean, J Adelstein, RS AF Cervantes, C. B. Lerma Tokuhiro, K. Zhang, Y. Conti, M. Bae, D. H. Daniels, M. Dean, J. Adelstein, R. S. TI A Point Mutation in Nonmuscle Myosin II-A Disrupts Mouse Spermatogenesis SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract CT ASCB/IFCB Meeting CY DEC 06-10, 2014 CL Philadelphia, PA SP Amer Soc Cell Biol, Int Federat Cell Biol C1 [Cervantes, C. B. Lerma; Zhang, Y.; Conti, M.; Adelstein, R. S.] NHLBI, Mol Cardiol Lab, Genet & Dev Biol Ctr, NIH, Bethesda, MD 20892 USA. [Tokuhiro, K.; Dean, J.] NIDDK, Cellular & Dev Biol Lab, NIH, Bethesda, MD 20892 USA. [Bae, D. H.; Daniels, M.] NHLBI, Electron Microscopy Core, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 EI 1939-4586 J9 MOL BIOL CELL JI Mol. Biol. Cell PD DEC PY 2014 VL 25 MA P2317 PG 1 WC Cell Biology SC Cell Biology GA CE8LP UT WOS:000352094105347 ER PT J AU Chang, J Lee, S Blackstone, CD AF Chang, J. Lee, S. Blackstone, C. D. TI Spastic paraplegia proteins spastizin and spatacsin mediate autophagic lysosome reformation SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract CT ASCB/IFCB Meeting CY DEC 06-10, 2014 CL Philadelphia, PA SP Amer Soc Cell Biol, Int Federat Cell Biol C1 [Chang, J.; Lee, S.; Blackstone, C. D.] NINDS, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 EI 1939-4586 J9 MOL BIOL CELL JI Mol. Biol. Cell PD DEC PY 2014 VL 25 MA P1224 PG 1 WC Cell Biology SC Cell Biology GA CE8LP UT WOS:000352094103075 ER PT J AU Chen, J Liu, J AF Chen, J. Liu, J. TI Spatio-temporal Model for Silencing of the Mitotic Spindle Assembly Checkpoint. SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract CT ASCB/IFCB Meeting CY DEC 06-10, 2014 CL Philadelphia, PA SP Amer Soc Cell Biol, Int Federat Cell Biol C1 [Chen, J.] NIH, Bethesda, MD 20892 USA. [Liu, J.] NHLBI, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 EI 1939-4586 J9 MOL BIOL CELL JI Mol. Biol. Cell PD DEC PY 2014 VL 25 MA P178 PG 1 WC Cell Biology SC Cell Biology GA CE8LP UT WOS:000352094100179 ER PT J AU Chua, J Senft, J Lockett, S Brett, P Burtnick, M Deshazer, D Friedlander, A AF Chua, J. Senft, J. Lockett, S. Brett, P. Burtnick, M. Deshazer, D. Friedlander, A. TI pH Alkalinization by Chloroquine Suppresses Burkholderia T6SS-1 Gene Expression, Phagosomal Escape and Multi-Nucleated Giant Cell Formation. SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract CT ASCB/IFCB Meeting CY DEC 06-10, 2014 CL Philadelphia, PA SP Amer Soc Cell Biol, Int Federat Cell Biol C1 [Chua, J.; Senft, J.; Deshazer, D.; Friedlander, A.] USAMRIID, Bacteriol, Ft Detrick, MD USA. [Lockett, S.] Frederick Natl Lab Canc Res, Opt Microscopy & Anal Lab, Frederick, MD USA. [Brett, P.] Univ S Alabama, Microbiol & Immunol, Mobile, AL 36688 USA. NR 0 TC 0 Z9 0 U1 1 U2 2 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 EI 1939-4586 J9 MOL BIOL CELL JI Mol. Biol. Cell PD DEC PY 2014 VL 25 MA P746 PG 2 WC Cell Biology SC Cell Biology GA CE8LP UT WOS:000352094101374 ER PT J AU Cohen-Fix, O Walters, A May, C Dauster, E Cinquin, B Smith, E Larabell, C AF Cohen-Fix, O. Walters, A. May, C. Dauster, E. Cinquin, B. Smith, E. Larabell, C. TI The budding yeast polo kinase, Cdc5, regulates domain-specific expansion of the nuclear envelope SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract CT ASCB/IFCB Meeting CY DEC 06-10, 2014 CL Philadelphia, PA SP Amer Soc Cell Biol, Int Federat Cell Biol C1 [Cohen-Fix, O.; Walters, A.; May, C.; Dauster, E.] NIDDK, NIH, Bethesda, MD 20892 USA. [Cinquin, B.; Smith, E.; Larabell, C.] Univ Calif San Francisco, Sch Med, Dept Anat, San Francisco, CA USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 EI 1939-4586 J9 MOL BIOL CELL JI Mol. Biol. Cell PD DEC PY 2014 VL 25 MA M100 PG 2 WC Cell Biology SC Cell Biology GA CE8LP UT WOS:000352094106197 ER PT J AU Conti, M Saleh, A Cornelius, S Van Waes, C Adelstein, RS AF Conti, M. Saleh, A. Cornelius, S. Van Waes, C. Adelstein, R. S. TI Conditional Deletion of Nonmuscle Myosin II-A Leads to Squamous Cell Carcinoma of the Tongue SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract CT ASCB/IFCB Meeting CY DEC 06-10, 2014 CL Philadelphia, PA SP Amer Soc Cell Biol, Int Federat Cell Biol C1 [Conti, M.; Adelstein, R. S.] NHLBI, Mol Cardiol Lab, Genet & Dev Biol Ctr, NIH, Bethesda, MD 20892 USA. [Saleh, A.; Cornelius, S.; Van Waes, C.] NIDCD, Clin Genom Unit, NIH, Bethesda, MD USA. [Saleh, A.; Cornelius, S.; Van Waes, C.] NIDCD, Tumor Biol Sect, Head & Neck Surg Branch, NIH, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 EI 1939-4586 J9 MOL BIOL CELL JI Mol. Biol. Cell PD DEC PY 2014 VL 25 MA P926 PG 1 WC Cell Biology SC Cell Biology GA CE8LP UT WOS:000352094102171 ER PT J AU Cruz, LA Vedula, P Gutierrez, N Abramczyk, R Ocegueda, M Petrie, RJ Rodriguez, AJ AF Cruz, L. A. Vedula, P. Gutierrez, N. Abramczyk, R. Ocegueda, M. Petrie, R. J. Rodriguez, A. J. TI Compartmentalized 3D colocalization analysis - a method to quantify epithelial adherens junction assembly. SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract CT ASCB/IFCB Meeting CY DEC 06-10, 2014 CL Philadelphia, PA SP Amer Soc Cell Biol, Int Federat Cell Biol C1 [Cruz, L. A.; Vedula, P.; Gutierrez, N.; Abramczyk, R.; Ocegueda, M.; Rodriguez, A. J.] Rutgers State Univ, Federated Dept Biol, Newark, NJ 07102 USA. [Petrie, R. J.] NIDCR, NIH, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 EI 1939-4586 J9 MOL BIOL CELL JI Mol. Biol. Cell PD DEC PY 2014 VL 25 MA P578 PG 1 WC Cell Biology SC Cell Biology GA CE8LP UT WOS:000352094101206 ER PT J AU Das, A Waterman, C AF Das, A. Waterman, C. TI Cytoskeletal integrity and acto-myosin contractility act by distinct pathways to regulate nuclear Yap1 localization and phosphorylation during mechanotransduction. SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract CT ASCB/IFCB Meeting CY DEC 06-10, 2014 CL Philadelphia, PA SP Amer Soc Cell Biol, Int Federat Cell Biol C1 [Das, A.] NHLBI, Cell Biol & Physiol, NIH, Bethesda, MD 20892 USA. [Waterman, C.] NHLBI, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 EI 1939-4586 J9 MOL BIOL CELL JI Mol. Biol. Cell PD DEC PY 2014 VL 25 MA P524 PG 1 WC Cell Biology SC Cell Biology GA CE8LP UT WOS:000352094101153 ER PT J AU Dasso, M Arnaoutov, A AF Dasso, M. Arnaoutov, A. TI IRBIT is a novel regulator of Ribonucleotide reductase in high eucaryotes SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract CT ASCB/IFCB Meeting CY DEC 06-10, 2014 CL Philadelphia, PA SP Amer Soc Cell Biol, Int Federat Cell Biol C1 [Dasso, M.; Arnaoutov, A.] NICHHD, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 EI 1939-4586 J9 MOL BIOL CELL JI Mol. Biol. Cell PD DEC PY 2014 VL 25 MA P218 PG 1 WC Cell Biology SC Cell Biology GA CE8LP UT WOS:000352094100219 ER PT J AU Dhingra, A Frost, LS Lopes, VS Rodriguez, IR Williams, DS Boesze-Battaglia, K AF Dhingra, A. Frost, L. S. Lopes, V. S. Rodriguez, I. R. Williams, D. S. Boesze-Battaglia, K. TI The Contribution of Melanoregulin to Microtubule-Associated Protein 1 Light Chain 3 (LC3) Associated Phagocytosis. SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract CT ASCB/IFCB Meeting CY DEC 06-10, 2014 CL Philadelphia, PA SP Amer Soc Cell Biol, Int Federat Cell Biol C1 [Dhingra, A.; Frost, L. S.; Boesze-Battaglia, K.] Univ Penn, Biochem, Philadelphia, PA 19104 USA. [Lopes, V. S.; Williams, D. S.] Univ Calif Los Angeles, Los Angeles, CA USA. [Rodriguez, I. R.] NEI, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 EI 1939-4586 J9 MOL BIOL CELL JI Mol. Biol. Cell PD DEC PY 2014 VL 25 MA P1365 PG 1 WC Cell Biology SC Cell Biology GA CE8LP UT WOS:000352094103216 ER PT J AU Dorward, DW Raae-Nielsen, J Hansen, BT Nair, V Fischer, ER AF Dorward, D. W. Raae-Nielsen, J. Hansen, B. T. Nair, V. Fischer, E. R. TI Device for microwave-enhanced processing of cryo-substitution for light and electron microscopy. SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract CT ASCB/IFCB Meeting CY DEC 06-10, 2014 CL Philadelphia, PA SP Amer Soc Cell Biol, Int Federat Cell Biol C1 [Dorward, D. W.; Raae-Nielsen, J.; Hansen, B. T.; Nair, V.; Fischer, E. R.] NIAID, RTB, Microscopy Unit, NIH,Rocky Mt Labs, Hamilton, MT USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 EI 1939-4586 J9 MOL BIOL CELL JI Mol. Biol. Cell PD DEC PY 2014 VL 25 MA P13 PG 2 WC Cell Biology SC Cell Biology GA CE8LP UT WOS:000352094100014 ER PT J AU Doyle, AD Yamada, KM Matsumoto, K AF Doyle, A. D. Yamada, K. M. Matsumoto, K. TI The local 3D microenvironment controls adhesion dynamics and cell motility by balancing forces at the leading edge. SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract CT ASCB/IFCB Meeting CY DEC 06-10, 2014 CL Philadelphia, PA SP Amer Soc Cell Biol, Int Federat Cell Biol C1 [Doyle, A. D.; Yamada, K. M.; Matsumoto, K.] NIDCR, NIH, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 EI 1939-4586 J9 MOL BIOL CELL JI Mol. Biol. Cell PD DEC PY 2014 VL 25 MA P522 PG 2 WC Cell Biology SC Cell Biology GA CE8LP UT WOS:000352094101151 ER PT J AU Dutta, D Donaldson, JG AF Dutta, D. Donaldson, J. G. TI Cross-talk between clathrin-mediated and clathrin-independent endosomal membrane systems coordinated by Rab35 and Arf6 SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract CT ASCB/IFCB Meeting CY DEC 06-10, 2014 CL Philadelphia, PA SP Amer Soc Cell Biol, Int Federat Cell Biol C1 [Dutta, D.; Donaldson, J. G.] NLHBI, Cell Biol & Physiol Ctr, NIH, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 EI 1939-4586 J9 MOL BIOL CELL JI Mol. Biol. Cell PD DEC PY 2014 VL 25 MA P1201 PG 1 WC Cell Biology SC Cell Biology GA CE8LP UT WOS:000352094103052 ER PT J AU Fabritius, AS Golden, A AF Fabritius, A. S. Golden, A. TI Defining genetic pathways of disease through genetic suppression screens in Caenorhabditis elegans. SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract CT ASCB/IFCB Meeting CY DEC 06-10, 2014 CL Philadelphia, PA SP Amer Soc Cell Biol, Int Federat Cell Biol C1 [Fabritius, A. S.; Golden, A.] NIDDK NIH, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 EI 1939-4586 J9 MOL BIOL CELL JI Mol. Biol. Cell PD DEC PY 2014 VL 25 MA P780 PG 2 WC Cell Biology SC Cell Biology GA CE8LP UT WOS:000352094102026 ER PT J AU Fischer, RS Elliott, HL Myers, KA Desai, RA Chen, CS Adelstein, RS Waterman, C Danuser, G AF Fischer, R. S. Elliott, H. L. Myers, K. A. Desai, R. A. Chen, C. S. Adelstein, R. S. Waterman, C. Danuser, G. TI Myosin II controls cellular branching morphogenesis and migration in 3D by responding to and minimizing cell surface curvature SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract CT ASCB/IFCB Meeting CY DEC 06-10, 2014 CL Philadelphia, PA SP Amer Soc Cell Biol, Int Federat Cell Biol C1 [Fischer, R. S.] NHLBI, Cell & Tissue Morphogenesis, Bethesda, MD 20892 USA. [Elliott, H. L.] Harvard Univ, Sch Med, Image & Data Anal Core, Boston, MA USA. [Myers, K. A.] Univ Sci, Misher Coll Arts & Sci, Dept Biol Sci, Philadelphia, PA USA. [Desai, R. A.] MRC NIMR, London, England. [Chen, C. S.] Boston Univ, Biomed Engn, Boston, MA 02215 USA. [Chen, C. S.] Harvard Univ, Wyss Inst Biologically Inspired Engn, Boston, MA USA. [Adelstein, R. S.] NHLBI, Mol Cardiol Lab, Genet & Dev Biol Ctr, NIH, Bethesda, MD 20892 USA. [Waterman, C.] NHLBI, NIH, Bethesda, MD 20892 USA. [Danuser, G.] Univ Texas SW Med Ctr Dallas, Dept Cell Biol, Dallas, TX 75390 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 EI 1939-4586 J9 MOL BIOL CELL JI Mol. Biol. Cell PD DEC PY 2014 VL 25 MA P940 PG 1 WC Cell Biology SC Cell Biology GA CE8LP UT WOS:000352094102185 ER PT J AU Fuentes, R Escobar-Aguirre, M Kugath, A Montecinos-Franjola, F Lopez, P Fernandez, J Mullins, MC AF Fuentes, R. Escobar-Aguirre, M. Kugath, A. Montecinos-Franjola, F. Lopez, P. Fernandez, J. Mullins, M. C. TI Cation/proton exchanger 1 protein (Cax1), a maternal-effect regulator of zebrafish cytoplasmic segregation and mRNA localization. SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract CT ASCB/IFCB Meeting CY DEC 06-10, 2014 CL Philadelphia, PA SP Amer Soc Cell Biol, Int Federat Cell Biol C1 [Fuentes, R.; Escobar-Aguirre, M.; Kugath, A.; Mullins, M. C.] Univ Penn, Dept Cell & Dev Biol, Philadelphia, PA 19104 USA. [Montecinos-Franjola, F.] NIH, LIMB, Bethesda, MD 20892 USA. [Lopez, P.; Fernandez, J.] Univ Chile, Dept Biol, Santiago, Chile. NR 0 TC 0 Z9 0 U1 0 U2 3 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 EI 1939-4586 J9 MOL BIOL CELL JI Mol. Biol. Cell PD DEC PY 2014 VL 25 MA P718 PG 2 WC Cell Biology SC Cell Biology GA CE8LP UT WOS:000352094101346 ER PT J AU Galletta, BJ Jacobs, KC Fagerstron, CJ Slep, KC Rusan, NM AF Galletta, B. J. Jacobs, K. C. Fagerstron, C. J. Slep, K. C. Rusan, N. M. TI A Detailed Centrosome Interactome Reveals a Novel Role for Asterless/CEP152 in Controlling Centriole Length Via Cep97. SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract CT ASCB/IFCB Meeting CY DEC 06-10, 2014 CL Philadelphia, PA SP Amer Soc Cell Biol, Int Federat Cell Biol C1 [Galletta, B. J.; Jacobs, K. C.; Fagerstron, C. J.; Rusan, N. M.] NHLBI, NIH, Bethesda, MD 20892 USA. [Slep, K. C.] Univ N Carolina, Dept Biol, Chapel Hill, NC USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 EI 1939-4586 J9 MOL BIOL CELL JI Mol. Biol. Cell PD DEC PY 2014 VL 25 MA P1738 PG 2 WC Cell Biology SC Cell Biology GA CE8LP UT WOS:000352094104203 ER PT J AU Gaspar, A Lucas, M Rojas, A Hierro, A Machner, M AF Gaspar, A. Lucas, M. Rojas, A. Hierro, A. Machner, M. TI A molecular mechanism for endosomal avoidance by the pathogen Legionella pneumophila. SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract CT ASCB/IFCB Meeting CY DEC 06-10, 2014 CL Philadelphia, PA SP Amer Soc Cell Biol, Int Federat Cell Biol C1 [Gaspar, A.; Machner, M.] NIH, Bethesda, MD 20892 USA. [Lucas, M.; Rojas, A.; Hierro, A.] CIC bioGUNE, Bilbao, Spain. NR 0 TC 0 Z9 0 U1 1 U2 2 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 EI 1939-4586 J9 MOL BIOL CELL JI Mol. Biol. Cell PD DEC PY 2014 VL 25 MA M50 PG 1 WC Cell Biology SC Cell Biology GA CE8LP UT WOS:000352094106099 ER PT J AU Gibbs, K Griffin, K AF Gibbs, K. Griffin, K. TI Biomedical Science Ph.D. Career Development and Interest Patterns by Race/Ethnicity and Gender. SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract CT ASCB/IFCB Meeting CY DEC 06-10, 2014 CL Philadelphia, PA SP Amer Soc Cell Biol, Int Federat Cell Biol C1 [Gibbs, K.] NCI, Bethesda, MD 20892 USA. [Griffin, K.] Univ Maryland, Counseling, Higher Educ, Special Educ, College Pk, MD 20742 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 EI 1939-4586 J9 MOL BIOL CELL JI Mol. Biol. Cell PD DEC PY 2014 VL 25 MA P791 PG 2 WC Cell Biology SC Cell Biology GA CE8LP UT WOS:000352094102037 ER PT J AU Glushakova, SE Wirth, CC Scheuermayer, M Leikina, E Humphrey, G Balaban, A Kachman, MM Pradel, G Zimmerberg, J AF Glushakova, S. E. Wirth, C. C. Scheuermayer, M. Leikina, E. Humphrey, G. Balaban, A. Kachman, M. M. Pradel, G. Zimmerberg, J. TI Release of malaria parasites from red blood cells requires parasite-derived pore-forming proteins. SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract CT ASCB/IFCB Meeting CY DEC 06-10, 2014 CL Philadelphia, PA SP Amer Soc Cell Biol, Int Federat Cell Biol C1 [Glushakova, S. E.; Leikina, E.; Humphrey, G.; Balaban, A.; Kachman, M. M.; Zimmerberg, J.] NICHHD, Program Phys Biol, NIH, Bethesda, MD 20892 USA. [Wirth, C. C.; Pradel, G.] Rhein Westfal TH Aachen, Inst Mol Biotechnol, Aachen, Germany. [Scheuermayer, M.] Univ Wurzburg, Res Ctr Infect Dis, D-97070 Wurzburg, Germany. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 EI 1939-4586 J9 MOL BIOL CELL JI Mol. Biol. Cell PD DEC PY 2014 VL 25 MA P2364 PG 1 WC Cell Biology SC Cell Biology GA CE8LP UT WOS:000352094105393 ER PT J AU Guha, M Srinivasan, S Ruthel, G Kashina, AS Carstens, R Mendoza, A Khanna, C Van Winkle, T Avadhani, NG AF Guha, M. Srinivasan, S. Ruthel, G. Kashina, A. S. Carstens, R. Mendoza, A. Khanna, C. Van Winkle, T. Avadhani, N. G. TI Mitochondrial retrograde signaling induces epithelial-mesenchymal transition and generates breast cancer stem cells SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract CT ASCB/IFCB Meeting CY DEC 06-10, 2014 CL Philadelphia, PA SP Amer Soc Cell Biol, Int Federat Cell Biol C1 [Guha, M.] Univ Penn, Anim Biol, Philadelphia, PA 19104 USA. [Srinivasan, S.; Ruthel, G.] Univ Penn, Philadelphia, PA 19104 USA. [Kashina, A. S.; Avadhani, N. G.] Univ Penn, Sch Vet Med, Dept Anim Biol, Philadelphia, PA 19104 USA. [Carstens, R.] Univ Penn, Dept Med, Perelman Sch Med, Philadelphia, PA 19104 USA. [Mendoza, A.; Khanna, C.] NIH, Tumor & Metastasis Biol Sect, Ctr Canc Res, Bethesda, MD 20892 USA. [Van Winkle, T.] Univ Penn, Sch Vet Med, Dept Pathobiol 3, Philadelphia, PA 19104 USA. NR 0 TC 0 Z9 0 U1 1 U2 2 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 EI 1939-4586 J9 MOL BIOL CELL JI Mol. Biol. Cell PD DEC PY 2014 VL 25 MA P1888 PG 2 WC Cell Biology SC Cell Biology GA CE8LP UT WOS:000352094104335 ER PT J AU Hanson, JC Chen, Y AF Hanson, J. C. Chen, Y. TI Induction of Carcinoma-Associated Fibroblasts in 3D Cell Coculture SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract CT ASCB/IFCB Meeting CY DEC 06-10, 2014 CL Philadelphia, PA SP Amer Soc Cell Biol, Int Federat Cell Biol C1 [Hanson, J. C.; Chen, Y.] NCI, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 EI 1939-4586 J9 MOL BIOL CELL JI Mol. Biol. Cell PD DEC PY 2014 VL 25 MA P1899 PG 1 WC Cell Biology SC Cell Biology GA CE8LP UT WOS:000352094104346 ER PT J AU Hardeman, EC Yang, L Kee, AJ Polishchuk, E Polishchuk, R Pleines, I Kile, B Weigert, R Gunning, PW AF Hardeman, E. C. Yang, L. Kee, A. J. Polishchuk, E. Polishchuk, R. Pleines, I. Kile, B. Weigert, R. Gunning, P. W. TI A novel actin filament population defined by the tropomyosin Tm4 regulates ER-to-Golgi trafficking. SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract CT ASCB/IFCB Meeting CY DEC 06-10, 2014 CL Philadelphia, PA SP Amer Soc Cell Biol, Int Federat Cell Biol C1 [Hardeman, E. C.; Yang, L.; Kee, A. J.; Gunning, P. W.] UNSW, Sch Med Sci, Sydney, NSW, Australia. [Polishchuk, E.; Polishchuk, R.] Telethon Inst Genet & Med, Naples, Italy. [Pleines, I.; Kile, B.] Water & Eliza Hall Inst, Melbourne, Vic, Australia. [Weigert, R.] NIDCR, NIH, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 EI 1939-4586 J9 MOL BIOL CELL JI Mol. Biol. Cell PD DEC PY 2014 VL 25 MA P1640 PG 1 WC Cell Biology SC Cell Biology GA CE8LP UT WOS:000352094104105 ER PT J AU Hayakawa, EH Tokumasu, F Usukura, J Matsuoka, H Tsuboi, T Wellems, TE AF Hayakawa, E. H. Tokumasu, F. Usukura, J. Matsuoka, H. Tsuboi, T. Wellems, T. E. TI Three dimensional structure of Maurer's cleft with tiny filaments in Plasmodium falciparum-infected Erythrocytes by "unroofing" method SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract CT ASCB/IFCB Meeting CY DEC 06-10, 2014 CL Philadelphia, PA SP Amer Soc Cell Biol, Int Federat Cell Biol C1 [Hayakawa, E. H.; Matsuoka, H.] Jichi Med Univ, Lab Med Zool & Parasitol, Shimotsuke, Japan. [Tokumasu, F.] Univ Tokyo, Dept Lipid, Tokyo, MD, Japan. [Usukura, J.] Nagoya Univ, Struct Biol Ctr, Nagoya, Aichi 4648601, Japan. [Tsuboi, T.] Ehime Univ, Cell Free Sci & Technol Res Ctr, Matsuyama, Ehime, Japan. [Wellems, T. E.] NIAID, Lab Malaria & Vector Res, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 EI 1939-4586 J9 MOL BIOL CELL JI Mol. Biol. Cell PD DEC PY 2014 VL 25 MA P2355 PG 1 WC Cell Biology SC Cell Biology GA CE8LP UT WOS:000352094105384 ER PT J AU Henderson, MJ Wires, ES Trychta, KA Richie, CT Yan, X Harvey, BK AF Henderson, M. J. Wires, E. S. Trychta, K. A. Richie, C. T. Yan, X. Harvey, B. K. TI Monitoring perturbations in endoplasmic reticulum calcium homeostasis using a novel secreted reporter protein. SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract CT ASCB/IFCB Meeting CY DEC 06-10, 2014 CL Philadelphia, PA SP Amer Soc Cell Biol, Int Federat Cell Biol C1 [Henderson, M. J.; Wires, E. S.; Trychta, K. A.; Richie, C. T.; Yan, X.; Harvey, B. K.] NIDA, NIH, Baltimore, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 EI 1939-4586 J9 MOL BIOL CELL JI Mol. Biol. Cell PD DEC PY 2014 VL 25 MA P43 PG 1 WC Cell Biology SC Cell Biology GA CE8LP UT WOS:000352094100044 ER PT J AU Hu, L Liu, J AF Hu, L. Liu, J. TI Mechanochemistry of persistent plasmid movement. SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract CT ASCB/IFCB Meeting CY DEC 06-10, 2014 CL Philadelphia, PA SP Amer Soc Cell Biol, Int Federat Cell Biol C1 [Hu, L.; Liu, J.] NHLBI, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 EI 1939-4586 J9 MOL BIOL CELL JI Mol. Biol. Cell PD DEC PY 2014 VL 25 MA P1513 PG 2 WC Cell Biology SC Cell Biology GA CE8LP UT WOS:000352094103364 ER PT J AU Insinna, C Lu, Q Ott, CM Baxa, U Lopes, S Lippincott-Schwartz, J Caplan, S Jackson, PK Westlake, CJ AF Insinna (Kettenhofen), C. Lu, Q. Ott, C. M. Baxa, U. Lopes, S. Lippincott-Schwartz, J. Caplan, S. Jackson, P. K. Westlake, C. J. TI EHD proteins coordinate membrane reorganization and fusion to initiate early steps of ciliogenesis. SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract CT ASCB/IFCB Meeting CY DEC 06-10, 2014 CL Philadelphia, PA SP Amer Soc Cell Biol, Int Federat Cell Biol C1 [Insinna (Kettenhofen), C.; Lu, Q.] NCI, LCDS, Frederick, MD 21701 USA. [Ott, C. M.] NICHD, NIH, Bethesda, MD USA. [Baxa, U.] NCI, NIH, Leidos, Frederick, MD 21701 USA. [Lopes, S.] CEDOC, Fac Ciencias Med, Lisbon, Portugal. [Lippincott-Schwartz, J.] Physiol Course Marine Biol Lab, Woods Hole, MA USA. [Lippincott-Schwartz, J.] NIH, Cell Biol & Metab program, NICHD, Bethesda, MD 20892 USA. [Caplan, S.] Univ Nebraska Med Ctr, Omaha, NE USA. [Jackson, P. K.] Stanford Univ, Sch Med, Dept Microbiol & Immunol, Stanford, CA 94305 USA. [Westlake, C. J.] NCI, Frederick, MD 21701 USA. NR 0 TC 0 Z9 0 U1 0 U2 2 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 EI 1939-4586 J9 MOL BIOL CELL JI Mol. Biol. Cell PD DEC PY 2014 VL 25 MA P993 PG 1 WC Cell Biology SC Cell Biology GA CE8LP UT WOS:000352094102238 ER PT J AU Jaramillo-Lambert, A Golden, A AF Jaramillo-Lambert, A. Golden, A. TI Identification and characterization of paternal-effect lethal mutants in C. elegans. SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract CT ASCB/IFCB Meeting CY DEC 06-10, 2014 CL Philadelphia, PA SP Amer Soc Cell Biol, Int Federat Cell Biol C1 [Jaramillo-Lambert, A.; Golden, A.] NIDDK, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 EI 1939-4586 J9 MOL BIOL CELL JI Mol. Biol. Cell PD DEC PY 2014 VL 25 MA P721 PG 1 WC Cell Biology SC Cell Biology GA CE8LP UT WOS:000352094101349 ER PT J AU Johnson, D Wilson, JM Donaldson, JG AF Johnson, D. Wilson, J. M. Donaldson, J. G. TI Clathrin Independent Endosomal Trafficking is required for T Cell Conjugate Formation and Activation. SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract CT ASCB/IFCB Meeting CY DEC 06-10, 2014 CL Philadelphia, PA SP Amer Soc Cell Biol, Int Federat Cell Biol C1 [Johnson, D.] Univ Arizona, Tucson, AZ USA. [Wilson, J. M.] Univ Arizona, Coll Med, Tucson, AZ USA. [Donaldson, J. G.] NHLBI, Cell Biol & Physiol Ctr, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 EI 1939-4586 J9 MOL BIOL CELL JI Mol. Biol. Cell PD DEC PY 2014 VL 25 MA P2040 PG 2 WC Cell Biology SC Cell Biology GA CE8LP UT WOS:000352094105069 ER PT J AU Joshi, AS Prinz, W AF Joshi, A. S. Prinz, W. TI Novel ER shaping proteins Pex30 and Pex31 are involved in pre-peroxisome vesicle biogenesis. SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract CT ASCB/IFCB Meeting CY DEC 06-10, 2014 CL Philadelphia, PA SP Amer Soc Cell Biol, Int Federat Cell Biol C1 [Joshi, A. S.; Prinz, W.] NIDDK, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 EI 1939-4586 J9 MOL BIOL CELL JI Mol. Biol. Cell PD DEC PY 2014 VL 25 MA P2095 PG 2 WC Cell Biology SC Cell Biology GA CE8LP UT WOS:000352094105124 ER PT J AU Jung, G Alexander, CJ Chen, B Betzig, E Hammer, JA AF Jung, G. Alexander, C. J. Chen, B. Betzig, E. Hammer, J. A. TI V-1/Myotrophin Regulates Capping Protein Activity in Vivo. SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract CT ASCB/IFCB Meeting CY DEC 06-10, 2014 CL Philadelphia, PA SP Amer Soc Cell Biol, Int Federat Cell Biol C1 [Jung, G.; Alexander, C. J.] NHLBI, NIH, Bethesda, MD 20892 USA. [Chen, B.; Betzig, E.] HHMI, Janelia Farm Res Campus, Ashburn, VA USA. [Hammer, J. A.] NHLBI, LCB, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 EI 1939-4586 J9 MOL BIOL CELL JI Mol. Biol. Cell PD DEC PY 2014 VL 25 MA P905 PG 2 WC Cell Biology SC Cell Biology GA CE8LP UT WOS:000352094102151 ER PT J AU Kane, LA Lazarou, M Fogel, AI Li, Y Yamano, K Sarraf, SA Banerjee, S Youle, RJ AF Kane, L. A. Lazarou, M. Fogel, A. I. Li, Y. Yamano, K. Sarraf, S. A. Banerjee, S. Youle, R. J. TI PINK1 is a ubiquitin kinase SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract CT ASCB/IFCB Meeting CY DEC 06-10, 2014 CL Philadelphia, PA SP Amer Soc Cell Biol, Int Federat Cell Biol C1 [Kane, L. A.; Lazarou, M.; Fogel, A. I.; Li, Y.; Yamano, K.; Sarraf, S. A.; Banerjee, S.; Youle, R. J.] NINDS, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 EI 1939-4586 J9 MOL BIOL CELL JI Mol. Biol. Cell PD DEC PY 2014 VL 25 MA P2140 PG 2 WC Cell Biology SC Cell Biology GA CE8LP UT WOS:000352094105169 ER PT J AU Kaushik, G Spenlehauer, A Sessions, AO Trujillo, A Fuhrmann, A Fu, Z Venkatraman, V Pohl, D Tuler, J Wang, M Lakatta, E Ocorr, K Bodmer, R Bernstein, S Van Eyk, J Cammarato, A Engler, AJ AF Kaushik, G. Spenlehauer, A. Sessions, A. O. Trujillo, A. Fuhrmann, A. Fu, Z. Venkatraman, V. Pohl, D. Tuler, J. Wang, M. Lakatta, E. Ocorr, K. Bodmer, R. Bernstein, S. Van Eyk, J. Cammarato, A. Engler, A. J. TI The vinculin network regulates cytoskeletal remodeling and contractile function in aging myocardium. SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract CT ASCB/IFCB Meeting CY DEC 06-10, 2014 CL Philadelphia, PA SP Amer Soc Cell Biol, Int Federat Cell Biol C1 [Kaushik, G.; Fuhrmann, A.; Engler, A. J.] Univ Calif San Diego, Bioengn, La Jolla, CA 92093 USA. [Spenlehauer, A.; Tuler, J.] Univ Calif San Diego, Bioengn, San Diego, CA 92103 USA. [Sessions, A. O.] Univ Calif San Diego, Biomed Sci, La Jolla, CA 92093 USA. [Trujillo, A.; Bernstein, S.] San Diego State Univ, San Diego, CA 92182 USA. [Fu, Z.; Venkatraman, V.; Van Eyk, J.] Johns Hopkins Univ, Sch Med, Cardiol, Baltimore, MD USA. [Pohl, D.] Iowa State Univ, Ames, IA USA. [Wang, M.; Lakatta, E.] NIA, Bethesda, MD 20892 USA. [Ocorr, K.; Bodmer, R.] Sanford Burnham Med Res Inst, La Jolla, CA USA. [Cammarato, A.] Johns Hopkins Univ, Med, Baltimore, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 EI 1939-4586 J9 MOL BIOL CELL JI Mol. Biol. Cell PD DEC PY 2014 VL 25 MA P1392 PG 2 WC Cell Biology SC Cell Biology GA CE8LP UT WOS:000352094103243 ER PT J AU Kim, LY Thompson, P Campbell, S Alushin, GM AF Kim, L. Y. Thompson, P. Campbell, S. Alushin, G. M. TI Structural Basis of the Vinculin-F-actin Interaction. SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract CT ASCB/IFCB Meeting CY DEC 06-10, 2014 CL Philadelphia, PA SP Amer Soc Cell Biol, Int Federat Cell Biol C1 [Kim, L. Y.; Alushin, G. M.] NHLBI, CBPC, NIH, Bethesda, MD 20892 USA. [Thompson, P.; Campbell, S.] UNC, Biochem & Biophys, Chapel Hill, NC USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 EI 1939-4586 J9 MOL BIOL CELL JI Mol. Biol. Cell PD DEC PY 2014 VL 25 MA P876 PG 2 WC Cell Biology SC Cell Biology GA CE8LP UT WOS:000352094102122 ER PT J AU Kim, YJ Guzman-Hernandez, ML Wisniewski, E Balla, T AF Kim, Yeun Ju Guzman-Hernandez, Maria-Luisa Wisniewski, Eva Balla, Tamas TI Nir2 plays a central role in ER-PM junctions maintaining Phosphoinositide Signaling Competence. SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract CT ASCB/IFCB Meeting CY DEC 06-10, 2014 CL Philadelphia, PA SP Amer Soc Cell Biol, Int Federat Cell Biol C1 [Kim, Yeun Ju; Guzman-Hernandez, Maria-Luisa; Wisniewski, Eva; Balla, Tamas] NICHD, Sect Mol Signal Transduct, Program Dev Neurosci, NIH, Bethesda, MD USA. RI Wisniewski, Eva/O-9233-2015 OI Wisniewski, Eva/0000-0001-8698-6867 NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 EI 1939-4586 J9 MOL BIOL CELL JI Mol. Biol. Cell PD DEC PY 2014 VL 25 MA P1332 PG 1 WC Cell Biology SC Cell Biology GA CE8LP UT WOS:000352094103183 ER PT J AU Kong, D Farmer, V Shukla, AK Loncarek, J AF Kong, D. Farmer, V. Shukla, A. K. Loncarek, J. TI Centriole maturation requires regulated Plk1 activity during two consecutive cell cycles. SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract CT ASCB/IFCB Meeting CY DEC 06-10, 2014 CL Philadelphia, PA SP Amer Soc Cell Biol, Int Federat Cell Biol C1 [Kong, D.; Farmer, V.; Shukla, A. K.; Loncarek, J.] NCI, NIH, Lab Prot Dynam & Signaling, Frederick, MD 21701 USA. RI Kong, Dong/O-4465-2016 OI Kong, Dong/0000-0002-7144-3808 NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 EI 1939-4586 J9 MOL BIOL CELL JI Mol. Biol. Cell PD DEC PY 2014 VL 25 MA P1020 PG 2 WC Cell Biology SC Cell Biology GA CE8LP UT WOS:000352094102265 ER PT J AU Korzeniowski, MK Wisniewski, E Holowka, DA Baird, B Balla, T AF Korzeniowski, M. K. Wisniewski, E. Holowka, D. A. Baird, B. Balla, T. TI Molecular Anatomy of Early Events in STIM1 Activation; Oligomerization or Conformational Change?. SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract CT ASCB/IFCB Meeting CY DEC 06-10, 2014 CL Philadelphia, PA SP Amer Soc Cell Biol, Int Federat Cell Biol C1 [Korzeniowski, M. K.; Holowka, D. A.; Baird, B.] Cornell Univ, Chem & Chem Biol, Ithaca, NY USA. [Wisniewski, E.; Balla, T.] NICHD, NIH, Bethesda, MD USA. RI Wisniewski, Eva/O-9233-2015 OI Wisniewski, Eva/0000-0001-8698-6867 NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 EI 1939-4586 J9 MOL BIOL CELL JI Mol. Biol. Cell PD DEC PY 2014 VL 25 MA P472 PG 1 WC Cell Biology SC Cell Biology GA CE8LP UT WOS:000352094101101 ER PT J AU Kotlyanskaya, L Giniger, E Kannan, R AF Kotlyanskaya, L. Giniger, E. Kannan, R. TI Disabled regulates Abelson nonreceptor tyrosine kinase localization and kinase activity in Drosophila. SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract CT ASCB/IFCB Meeting CY DEC 06-10, 2014 CL Philadelphia, PA SP Amer Soc Cell Biol, Int Federat Cell Biol C1 [Kotlyanskaya, L.] Univ N Carolina, Neurobiol Curriculum, Bethesda, MD USA. [Giniger, E.; Kannan, R.] NINDS Inst, NIH, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 EI 1939-4586 J9 MOL BIOL CELL JI Mol. Biol. Cell PD DEC PY 2014 VL 25 MA P77 PG 1 WC Cell Biology SC Cell Biology GA CE8LP UT WOS:000352094100078 ER PT J AU Lakdawala, S Wu, Y Wawrzusin, P Broadbent, A Kabat, J Lamirande, E Fodor, E Altan-Bonnet, N Shroff, H Subbarao, K AF Lakdawala, S. Wu, Y. Wawrzusin, P. Broadbent, A. Kabat, J. Lamirande, E. Fodor, E. Altan-Bonnet, N. Shroff, H. Subbarao, K. TI Influenza A Virus Assembly Intermediates Fuse in the Cytoplasm. SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract CT ASCB/IFCB Meeting CY DEC 06-10, 2014 CL Philadelphia, PA SP Amer Soc Cell Biol, Int Federat Cell Biol C1 [Lakdawala, S.; Broadbent, A.; Lamirande, E.; Subbarao, K.] NIAID, Infect Dis Lab, NIH, Bethesda, MD 20892 USA. [Wu, Y.; Wawrzusin, P.; Shroff, H.] NIBIB, Sect High Resolut Opt Imaging, NIH, Bethesda, MD USA. [Kabat, J.] NIAID, Res Technol Branch, NIH, Bethesda, MD 20892 USA. [Fodor, E.] Univ Oxford, Sir William Dunn Sch Pathol, Oxford OX1 3RE, England. [Altan-Bonnet, N.] NHLBI, NIH, Bethesda, MD 20892 USA. RI Shroff, Hari/E-7247-2016 OI Shroff, Hari/0000-0003-3613-8215 NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 EI 1939-4586 J9 MOL BIOL CELL JI Mol. Biol. Cell PD DEC PY 2014 VL 25 MA E38 PG 1 WC Cell Biology SC Cell Biology GA CE8LP UT WOS:000352094106043 ER PT J AU Lakdawala, S Wu, Y Wawrzusin, P Broadbent, A Kabat, J Lamirande, E Fodor, E Altan-Bonnet, N Shroff, H Subbarao, K AF Lakdawala, S. Wu, Y. Wawrzusin, P. Broadbent, A. Kabat, J. Lamirande, E. Fodor, E. Altan-Bonnet, N. Shroff, H. Subbarao, K. TI Influenza A Virus Assembly Intermediates Fuse in the Cytoplasm. SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract CT ASCB/IFCB Meeting CY DEC 06-10, 2014 CL Philadelphia, PA SP Amer Soc Cell Biol, Int Federat Cell Biol C1 [Lakdawala, S.; Broadbent, A.; Lamirande, E.; Subbarao, K.] NIAID, Infect Dis Lab, NIH, Bethesda, MD 20892 USA. [Wu, Y.; Wawrzusin, P.; Shroff, H.] NIBIB, Sect High Resolut Opt Imaging, Bethesda, MD USA. [Kabat, J.] NIAID, Res Technol Branch, NIH, Bethesda, MD 20892 USA. [Fodor, E.] Univ Oxford, Sir William Dunn Sch Pathol, Oxford OX1 3RE, England. [Altan-Bonnet, N.] NHLBI, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 EI 1939-4586 J9 MOL BIOL CELL JI Mol. Biol. Cell PD DEC PY 2014 VL 25 MA P1236 PG 2 WC Cell Biology SC Cell Biology GA CE8LP UT WOS:000352094103087 ER PT J AU Lee, S Chang, J Blackstone, CD AF Lee, S. Chang, J. Blackstone, C. D. TI FAM21 regulates recycling of SNX27-retromer cargoes to the plasma membrane. SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract CT ASCB/IFCB Meeting CY DEC 06-10, 2014 CL Philadelphia, PA SP Amer Soc Cell Biol, Int Federat Cell Biol C1 [Lee, S.; Chang, J.; Blackstone, C. D.] NINDS, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 EI 1939-4586 J9 MOL BIOL CELL JI Mol. Biol. Cell PD DEC PY 2014 VL 25 MA P2046 PG 2 WC Cell Biology SC Cell Biology GA CE8LP UT WOS:000352094105075 ER PT J AU Lerit, DA Poulton, JS Jordan, HA Peifer, M Rusan, NM AF Lerit, D. A. Poulton, J. S. Jordan, H. A. Peifer, M. Rusan, N. M. TI PLP forms novel centriole satellites and is critical for embryonic development. SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract CT ASCB/IFCB Meeting CY DEC 06-10, 2014 CL Philadelphia, PA SP Amer Soc Cell Biol, Int Federat Cell Biol C1 [Lerit, D. A.; Jordan, H. A.; Rusan, N. M.] NHLBI, Cell Biol & Physiol Ctr, NIH, Bethesda, MD 20892 USA. [Poulton, J. S.; Peifer, M.] Univ N Carolina, Dept Biol, Chapel Hill, NC USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 EI 1939-4586 J9 MOL BIOL CELL JI Mol. Biol. Cell PD DEC PY 2014 VL 25 MA P1024 PG 1 WC Cell Biology SC Cell Biology GA CE8LP UT WOS:000352094102269 ER PT J AU Li, Z AF Li, Z. TI Regulation of synaptic vesicles by the mitochondria-caspase-autohpagy pathway. SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract CT ASCB/IFCB Meeting CY DEC 06-10, 2014 CL Philadelphia, PA SP Amer Soc Cell Biol, Int Federat Cell Biol C1 [Li, Z.] NIMH, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 EI 1939-4586 J9 MOL BIOL CELL JI Mol. Biol. Cell PD DEC PY 2014 VL 25 MA P1294 PG 1 WC Cell Biology SC Cell Biology GA CE8LP UT WOS:000352094103145 ER PT J AU Lin, M Sheng, Z AF Lin, M. Sheng, Z. TI Mechanism Removing Damaged Mitochondria from Axonal Terminals. SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract CT ASCB/IFCB Meeting CY DEC 06-10, 2014 CL Philadelphia, PA SP Amer Soc Cell Biol, Int Federat Cell Biol C1 [Lin, M.; Sheng, Z.] NINDS, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 EI 1939-4586 J9 MOL BIOL CELL JI Mol. Biol. Cell PD DEC PY 2014 VL 25 MA P1339 PG 1 WC Cell Biology SC Cell Biology GA CE8LP UT WOS:000352094103190 ER PT J AU Liu, L AF Liu, L. TI Role of ER-Golgi contact sites in sphingolipid synthesis in yeast. SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract CT ASCB/IFCB Meeting CY DEC 06-10, 2014 CL Philadelphia, PA SP Amer Soc Cell Biol, Int Federat Cell Biol C1 [Liu, L.] NIDDK, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 EI 1939-4586 J9 MOL BIOL CELL JI Mol. Biol. Cell PD DEC PY 2014 VL 25 MA P1331 PG 2 WC Cell Biology SC Cell Biology GA CE8LP UT WOS:000352094103182 ER PT J AU Loew, M Sackett, DL Bane, SL AF Loew, M. Sackett, D. L. Bane, S. L. TI Interaction of Colchicine-Site Drugs with beta VI-Isotype of Tubulin. SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract CT ASCB/IFCB Meeting CY DEC 06-10, 2014 CL Philadelphia, PA SP Amer Soc Cell Biol, Int Federat Cell Biol C1 [Loew, M.; Bane, S. L.] SUNY Binghamton, Chem, Binghamton, NY USA. [Sackett, D. L.] NICHD, Program Phys Biol, NIH, Bethesda, MD USA. RI Bane, Susan/C-1414-2013 OI Bane, Susan/0000-0002-4270-6314 NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 EI 1939-4586 J9 MOL BIOL CELL JI Mol. Biol. Cell PD DEC PY 2014 VL 25 MA P137 PG 1 WC Cell Biology SC Cell Biology GA CE8LP UT WOS:000352094100138 ER PT J AU Logue, J Cartagena-Rivera, A Chadwick, R Waterman, C AF Logue, J. Cartagena-Rivera, A. Chadwick, R. Waterman, C. TI Bundling of the actin cortex by Erk phosphorylated Eps8 is essential for high cortex tension and the bleb-based migration of melanoma cells SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract CT ASCB/IFCB Meeting CY DEC 06-10, 2014 CL Philadelphia, PA SP Amer Soc Cell Biol, Int Federat Cell Biol C1 [Logue, J.] NHLBI, NIDCD, NIH, Bethesda, MD 20892 USA. [Cartagena-Rivera, A.; Chadwick, R.] NIDCD, NIH, Bethesda, MD USA. [Waterman, C.] NHLBI, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 EI 1939-4586 J9 MOL BIOL CELL JI Mol. Biol. Cell PD DEC PY 2014 VL 25 MA P248 PG 1 WC Cell Biology SC Cell Biology GA CE8LP UT WOS:000352094100267 ER PT J AU Ma, X Uchida, Y Bowen, C Mukoyama, Y Adelstein, RS AF Ma, X. Uchida, Y. Bowen, C. Mukoyama, Y. Adelstein, R. S. TI The Role of Nonmuscle Myosin II-A and II-B in Coronary Vessel Development in Mice. 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TI Triple miRNA Shank knockdown shows that Shank-cortactin interactions control actin dynamics in neuronal spines and synapses. SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract CT ASCB/IFCB Meeting CY DEC 06-10, 2014 CL Philadelphia, PA SP Amer Soc Cell Biol, Int Federat Cell Biol C1 [MacGillavry, H. D.] Univ Utrecht, Cell Biol, Utrecht, Netherlands. [Kerr, J. M.] NINDS, NIH, Bethesda, MD 20892 USA. [Frost, N. A.] UCSF, Sch Med, Psychiat, San Francisco, CA USA. [Blanpied, T. A.] Univ Maryland, Sch Med, Dept Physiol, Baltimore, MD 21201 USA. [Blanpied, T. A.] Univ Maryland, Sch Med, Program Neurosci, Baltimore, MD 21201 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 EI 1939-4586 J9 MOL BIOL CELL JI Mol. Biol. Cell PD DEC PY 2014 VL 25 MA P2090 PG 2 WC Cell Biology SC Cell Biology GA CE8LP UT WOS:000352094105119 ER PT J AU Majumdar, R Tavakoli-Tameh, A Kriebel, P Parent, CA AF Majumdar, R. Tavakoli-Tameh, A. Kriebel, P. Parent, C. A. TI Exosomes mediate LTB4 signal relay during neutrophil chemotaxis. SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract CT ASCB/IFCB Meeting CY DEC 06-10, 2014 CL Philadelphia, PA SP Amer Soc Cell Biol, Int Federat Cell Biol C1 [Majumdar, R.; Tavakoli-Tameh, A.; Kriebel, P.; Parent, C. A.] NCI, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 EI 1939-4586 J9 MOL BIOL CELL JI Mol. Biol. Cell PD DEC PY 2014 VL 25 MA P553 PG 2 WC Cell Biology SC Cell Biology GA CE8LP UT WOS:000352094101182 ER PT J AU Malide, D AF Malide, D. TI In vivo tracking of label-free resident cells in murine tissues via third harmonic generation microscopy. SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract CT ASCB/IFCB Meeting CY DEC 06-10, 2014 CL Philadelphia, PA SP Amer Soc Cell Biol, Int Federat Cell Biol C1 [Malide, D.] NHLBI, Light Microscopy Core Facil, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 EI 1939-4586 J9 MOL BIOL CELL JI Mol. Biol. Cell PD DEC PY 2014 VL 25 MA P23 PG 2 WC Cell Biology SC Cell Biology GA CE8LP UT WOS:000352094100024 ER PT J AU Manor, U Bartholomew, S Higgs, H Spudich, JA Lippincott-Schwartz, J AF Manor, U. Bartholomew, S. Higgs, H. Spudich, J. A. Lippincott-Schwartz, J. TI Spire1C promotes actin- and ER-mediated mitochondria constriction and fission SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract CT Joint Annual Meeting of the American-Society-for-Cell-Biology (ASCB) / International-Federation-for-Cell-Biology (IFCB) CY DEC 06-10, 2014 CL Philadelphia, PA SP Amer Soc Cell Biol, Int Federat Cell Biol C1 [Manor, U.] NICHD, Cell Biol & Metab, NIH, Bethesda, MD USA. [Bartholomew, S.; Spudich, J. A.] Stanford Univ, Stanford, CA 94305 USA. [Higgs, H.] Dartmouth Coll, Geisel Sch Med, Dept Biochem, Hanover, NH 03755 USA. [Lippincott-Schwartz, J.] Marine Biol Lab, Physiol Course, Woods Hole, MA 02543 USA. [Lippincott-Schwartz, J.] NICHD, Cell Biol & Metab Program, NIH, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 EI 1939-4586 J9 MOL BIOL CELL JI Mol. Biol. Cell PD DEC PY 2014 VL 25 MA P2134 PG 1 WC Cell Biology SC Cell Biology GA CE8LP UT WOS:000352094105163 ER PT J AU Markossian, S Arnaoutov, A Larionov, V Dasso, M AF Markossian, S. Arnaoutov, A. Larionov, V. Dasso, M. TI Quantitative Assessment of Chromosome Instability Promoted by Chemotherapeutic Agents. SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract CT ASCB/IFCB Meeting CY DEC 06-10, 2014 CL Philadelphia, PA SP Amer Soc Cell Biol, Int Federat Cell Biol C1 [Markossian, S.; Arnaoutov, A.; Dasso, M.] NICHHD, NIH, Bethesda, MD 20892 USA. [Larionov, V.] NCI, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 EI 1939-4586 J9 MOL BIOL CELL JI Mol. Biol. Cell PD DEC PY 2014 VL 25 MA P1818 PG 2 WC Cell Biology SC Cell Biology GA CE8LP UT WOS:000352094104283 ER PT J AU Marteil, G Guerrero, A Godinho, S Machado, P Loncarek, J Mendonca, S Fonseca, I Pellman, D Bettencourt-Dias, M AF Marteil, G. Guerrero, A. Godinho, S. Machado, P. Loncarek, J. Mendonca, S. Fonseca, I. Pellman, D. Bettencourt-Dias, M. TI Cancer-wide survey of centrosomes reveals centriole fragmentation as a novel origin of supernumerary centrosomes. SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract CT ASCB/IFCB Meeting CY DEC 06-10, 2014 CL Philadelphia, PA SP Amer Soc Cell Biol, Int Federat Cell Biol C1 [Marteil, G.; Machado, P.; Mendonca, S.; Fonseca, I.; Bettencourt-Dias, M.] Gulbenkian Inst Sci, Oeiras, Portugal. [Guerrero, A.] Univ Nacl Autonoma Mexico, Inst Biotechnol, Oeiras, Portugal. [Godinho, S.] Barts Canc Inst, London, England. [Machado, P.] EMBL, Heidelberg, Germany. [Loncarek, J.] NCI, NIH, Lab Prot Dynam & Signaling, Frederick, MD 21701 USA. 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G.; Inglese, J.] NCATS, Assay Dev & Screening Technol ADST Lab, NIH, Rockville, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 EI 1939-4586 J9 MOL BIOL CELL JI Mol. Biol. Cell PD DEC PY 2014 VL 25 MA P544 PG 1 WC Cell Biology SC Cell Biology GA CE8LP UT WOS:000352094101173 ER PT J AU Meng, L Park, J Kim, T Lee, K AF Meng, L. Park, J. Kim, T. Lee, K. TI Plk1 binds to the two distinct phospho-motifs on a centrosomal scaffold, Cep192, to promote bipolar spindle formation. SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract CT ASCB/IFCB Meeting CY DEC 06-10, 2014 CL Philadelphia, PA SP Amer Soc Cell Biol, Int Federat Cell Biol C1 [Meng, L.] NIH, Bethesda, MD 20892 USA. [Park, J.; Kim, T.; Lee, K.] NCI, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 EI 1939-4586 J9 MOL BIOL CELL JI Mol. Biol. Cell PD DEC PY 2014 VL 25 MA P167 PG 2 WC Cell Biology SC Cell Biology GA CE8LP UT WOS:000352094100168 ER PT J AU Meseroll, RA Cohen-Fix, O AF Meseroll, R. A. Cohen-Fix, O. TI A genetic screen reveals the requirement for mRNA processing genes and the topoisomerase TOP2 in nuclear morphology. SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract CT ASCB/IFCB Meeting CY DEC 06-10, 2014 CL Philadelphia, PA SP Amer Soc Cell Biol, Int Federat Cell Biol C1 [Meseroll, R. A.; Cohen-Fix, O.] NIDDK, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 EI 1939-4586 J9 MOL BIOL CELL JI Mol. Biol. Cell PD DEC PY 2014 VL 25 MA P1180 PG 1 WC Cell Biology SC Cell Biology GA CE8LP UT WOS:000352094103031 ER PT J AU Milgroom, A Ralston, E AF Milgroom, A. Ralston, E. TI Optical clearing of mouse skeletal muscle with the CLARITY method. SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract CT ASCB/IFCB Meeting CY DEC 06-10, 2014 CL Philadelphia, PA SP Amer Soc Cell Biol, Int Federat Cell Biol C1 [Milgroom, A.; Ralston, E.] NIAMS, NIH, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 2 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 EI 1939-4586 J9 MOL BIOL CELL JI Mol. Biol. Cell PD DEC PY 2014 VL 25 MA P42 PG 2 WC Cell Biology SC Cell Biology GA CE8LP UT WOS:000352094100043 ER PT J AU Mo, M Dasso, M Arnaoutov, A AF Mo, M. Dasso, M. Arnaoutov, A. TI Phosphorylation of Xenopus p31comet potentiates mitotic checkpoint exit SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract CT ASCB/IFCB Meeting CY DEC 06-10, 2014 CL Philadelphia, PA SP Amer Soc Cell Biol, Int Federat Cell Biol C1 [Mo, M.] NIH, Bethesda, MD 20892 USA. [Dasso, M.; Arnaoutov, A.] NICHHD, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 EI 1939-4586 J9 MOL BIOL CELL JI Mol. Biol. Cell PD DEC PY 2014 VL 25 MA P231 PG 1 WC Cell Biology SC Cell Biology GA CE8LP UT WOS:000352094100232 ER PT J AU Molina, O Shah, P Kouprina, N Larionov, V Earnshaw, WC AF Molina, O. Shah, P. Kouprina, N. Larionov, V. Earnshaw, W. C. TI Construction of Human Artificial Chromosomes in a non-transformed cell line. 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SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract CT ASCB/IFCB Meeting CY DEC 06-10, 2014 CL Philadelphia, PA SP Amer Soc Cell Biol, Int Federat Cell Biol C1 [Morsci, N.; Sheng, Z.] NINDS, NIH, Bethesda, MD 20892 USA. [Hall, D. H.] Albert Einstein Coll Med, Nrurosci, Bronx, NY 10467 USA. [Driscoll, M.] Rutgers State Univ, Mol Biol & Biochem, Piscataway, NJ USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 EI 1939-4586 J9 MOL BIOL CELL JI Mol. Biol. Cell PD DEC PY 2014 VL 25 MA P1338 PG 2 WC Cell Biology SC Cell Biology GA CE8LP UT WOS:000352094103189 ER PT J AU Mukherjee, K Chio, TI Sorrentino, AM Sackett, DL Bane, SL AF Mukherjee, K. Chio, T. I. Sorrentino, A. M. Sackett, D. L. Bane, S. L. TI One Step Detection of Oxidative Stress-Induced Carbonylation in Live Mammalian Cells. SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract CT ASCB/IFCB Meeting CY DEC 06-10, 2014 CL Philadelphia, PA SP Amer Soc Cell Biol, Int Federat Cell Biol C1 [Mukherjee, K.; Chio, T. I.; Sorrentino, A. M.; Bane, S. L.] SUNY Binghamton, Chem, Binghamton, NY USA. [Sackett, D. L.] NICHD, Program Phys Biol, NIH, Bethesda, MD USA. RI Bane, Susan/C-1414-2013 OI Bane, Susan/0000-0002-4270-6314 NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 EI 1939-4586 J9 MOL BIOL CELL JI Mol. Biol. Cell PD DEC PY 2014 VL 25 MA P670 PG 2 WC Cell Biology SC Cell Biology GA CE8LP UT WOS:000352094101298 ER PT J AU Murugesan, S Yi, J Li, D Shao, L Betzig, E Wu, X Hammer, JA AF Murugesan, S. Yi, J. Li, D. Shao, L. Betzig, E. Wu, X. Hammer, J. A. TI An Alternative Mechanism for Actin Arc Formation at the Immunological Synapse of Jurkat T cells. SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract CT ASCB/IFCB Meeting CY DEC 06-10, 2014 CL Philadelphia, PA SP Amer Soc Cell Biol, Int Federat Cell Biol C1 [Murugesan, S.; Yi, J.; Wu, X.; Hammer, J. A.] NHLBI, NIH, Bethesda, MD 20892 USA. [Li, D.; Shao, L.; Betzig, E.] HHMI, Ashburn, VA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 EI 1939-4586 J9 MOL BIOL CELL JI Mol. Biol. Cell PD DEC PY 2014 VL 25 MA P44 PG 1 WC Cell Biology SC Cell Biology GA CE8LP UT WOS:000352094100045 ER PT J AU Nezich, C Fogel, AI Wang, C Youle, RJ AF Nezich, C. Fogel, A. I. Wang, C. Youle, R. J. TI Parkin regulates the activity of MiTF/TFE transcription factors independent of mTORC1 during mitophagy SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract CT ASCB/IFCB Meeting CY DEC 06-10, 2014 CL Philadelphia, PA SP Amer Soc Cell Biol, Int Federat Cell Biol C1 [Nezich, C.; Fogel, A. 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NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 EI 1939-4586 J9 MOL BIOL CELL JI Mol. Biol. Cell PD DEC PY 2014 VL 25 MA P2394 PG 2 WC Cell Biology SC Cell Biology GA CE8LP UT WOS:000352094105422 ER PT J AU Ohman, R Brubaker, L Kawakami-Schulz, S Lin, X Subedi, K Chow, I Kaufman, J Wingfield, P Mankodi, AK AF Ohman, R. Brubaker, L. Kawakami-Schulz, S. Lin, X. Subedi, K. Chow, I. Kaufman, J. Wingfield, P. Mankodi, A. K. TI Isoform-specific oligomerization of ZASP, a myofibrillar myopathy gene product, in vitro and in vivo. SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract CT ASCB/IFCB Meeting CY DEC 06-10, 2014 CL Philadelphia, PA SP Amer Soc Cell Biol, Int Federat Cell Biol C1 [Ohman, R.; Brubaker, L.; Kawakami-Schulz, S.; Lin, X.; Subedi, K.; Chow, I.; Mankodi, A. K.] NINDS, NIH, Bethesda, MD 20892 USA. [Kaufman, J.; Wingfield, P.] NIAMS, NIH, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 2 U2 3 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 EI 1939-4586 J9 MOL BIOL CELL JI Mol. Biol. Cell PD DEC PY 2014 VL 25 MA P79 PG 2 WC Cell Biology SC Cell Biology GA CE8LP UT WOS:000352094100080 ER PT J AU Ojha, N Choudhary, V Prinz, W AF Ojha, N. Choudhary, V. Prinz, W. TI A dynamin-like ER-shaping protein and FIT proteins regulate lipid droplet biogenesis in yeast SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract CT ASCB/IFCB Meeting CY DEC 06-10, 2014 CL Philadelphia, PA SP Amer Soc Cell Biol, Int Federat Cell Biol C1 [Ojha, N.; Choudhary, V.; Prinz, W.] NIDDK, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 EI 1939-4586 J9 MOL BIOL CELL JI Mol. Biol. Cell PD DEC PY 2014 VL 25 MA P2118 PG 1 WC Cell Biology SC Cell Biology GA CE8LP UT WOS:000352094105147 ER PT J AU Ott, CM Battle, C Lippincott-Schwartz, J Schmidt, CF AF Ott, C. M. Battle, C. Lippincott-Schwartz, J. Schmidt, C. F. TI Primary cilia bend and pivot in response to intracellular and extracellular forces. SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract CT Joint Annual Meeting of the American-Society-for-Cell-Biology (ASCB) / International-Federation-for-Cell-Biology (IFCB) CY DEC 06-10, 2014 CL Philadelphia, PA SP Amer Soc Cell Biol, Int Federat Cell Biol C1 [Ott, C. M.] NICHD, NIH, Bethesda, MD USA. [Battle, C.] Univ Gottingen, Drittes Phys Inst, Gottingen, Germany. [Lippincott-Schwartz, J.] Marine Biol Lab, Physiol Course, Woods Hole, MA 02543 USA. [Lippincott-Schwartz, J.] NICHD, Cell Biol & Metab Program, NIH, Bethesda, MD USA. [Schmidt, C. F.] Univ Gottingen, Phys Inst Biophys, D-37073 Gottingen, Germany. RI Schmidt, Christoph/G-3787-2011 OI Schmidt, Christoph/0000-0003-2864-6973 NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 EI 1939-4586 J9 MOL BIOL CELL JI Mol. Biol. Cell PD DEC PY 2014 VL 25 MA P1764 PG 1 WC Cell Biology SC Cell Biology GA CE8LP UT WOS:000352094104229 ER PT J AU Park, C Park, J Kim, T Lee, K AF Park, C. Park, J. Kim, T. Lee, K. TI Plk1-dependent timely delocalization of the PBIP1-CENP-Q complex from kinetochores is critical for proper chromosome segregation. SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract CT ASCB/IFCB Meeting CY DEC 06-10, 2014 CL Philadelphia, PA SP Amer Soc Cell Biol, Int Federat Cell Biol C1 [Park, C.] Korea Res Inst Chem Technol, Taejon 305606, South Korea. [Park, J.; Kim, T.; Lee, K.] NCI, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 EI 1939-4586 J9 MOL BIOL CELL JI Mol. Biol. Cell PD DEC PY 2014 VL 25 MA P1052 PG 1 WC Cell Biology SC Cell Biology GA CE8LP UT WOS:000352094102297 ER PT J AU Park, J Park, S Kim, T Kim, J Kwak, M Ku, B Tian, L Kim, S Oh, B Yang, W Lee, K AF Park, J. Park, S. Kim, T. Kim, J. Kwak, M. Ku, B. Tian, L. Kim, S. Oh, B. Yang, W. Lee, K. TI Molecular basis of ordered Plk4 binding to two distinct scaffolds critical for centriole biogenesis. SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract CT ASCB/IFCB Meeting CY DEC 06-10, 2014 CL Philadelphia, PA SP Amer Soc Cell Biol, Int Federat Cell Biol C1 [Park, J.; Park, S.; Kim, T.; Lee, K.] NCI, NIH, Bethesda, MD 20892 USA. [Kim, J.; Ku, B.; Kim, S.] Korea Res Inst Biosci & Biotechnol, Taejon, South Korea. [Kwak, M.; Oh, B.] Korea Adv Inst Sci & Technologycience & Biotechno, Daejeon, South Korea. 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Cell PD DEC PY 2014 VL 25 MA P1031 PG 1 WC Cell Biology SC Cell Biology GA CE8LP UT WOS:000352094102276 ER PT J AU Petrie, R Koo, H Yamada, K AF Petrie, R. Koo, H. Yamada, K. TI Myosin II pulls the nucleus forward to increase intracellular pressure and drive 3D cell movement. SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract CT ASCB/IFCB Meeting CY DEC 06-10, 2014 CL Philadelphia, PA SP Amer Soc Cell Biol, Int Federat Cell Biol C1 [Petrie, R.; Yamada, K.] NIDCR, NIH, Bethesda, MD USA. [Koo, H.] Univ Penn, Sch Dent Med, Dept Orthodont, Philadelphia, PA 19104 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 EI 1939-4586 J9 MOL BIOL CELL JI Mol. Biol. Cell PD DEC PY 2014 VL 25 MA P523 PG 1 WC Cell Biology SC Cell Biology GA CE8LP UT WOS:000352094101152 ER PT J AU Plevock, KM Guillen, RX Galletta, BJ Slep, KC Rusan, NM AF Plevock, K. M. Guillen, R. X. Galletta, B. J. Slep, K. C. Rusan, N. M. TI CP190-microtubule association is mediated by a novel N-terminal region that requires dimerization mediated by a flanking BTB domain. SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract CT ASCB/IFCB Meeting CY DEC 06-10, 2014 CL Philadelphia, PA SP Amer Soc Cell Biol, Int Federat Cell Biol C1 [Plevock, K. M.] Univ N Carolina, Chapel Hill, NC USA. [Plevock, K. M.; Guillen, R. X.; Galletta, B. J.; Rusan, N. M.] NHLBI, NIH, Bethesda, MD 20892 USA. [Slep, K. C.] Univ N Carolina, Dept Biol, Chapel Hill, NC USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 EI 1939-4586 J9 MOL BIOL CELL JI Mol. Biol. Cell PD DEC PY 2014 VL 25 MA P119 PG 2 WC Cell Biology SC Cell Biology GA CE8LP UT WOS:000352094100120 ER PT J AU Porat-Shliom, N Chen, Y Shitara, A Tora, M Harding, O Masedunskas, A Weigert, R AF Porat-Shliom, N. Chen, Y. Shitara, A. Tora, M. Harding, O. Masedunskas, A. Weigert, R. TI In vivo tissue-wide synchronization of mitochondrial metabolic oscillations SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract CT ASCB/IFCB Meeting CY DEC 06-10, 2014 CL Philadelphia, PA SP Amer Soc Cell Biol, Int Federat Cell Biol C1 [Porat-Shliom, N.; Shitara, A.; Tora, M.; Harding, O.; Masedunskas, A.; Weigert, R.] NIDCR, NIH, Bethesda, MD USA. [Chen, Y.] NCI, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 EI 1939-4586 J9 MOL BIOL CELL JI Mol. Biol. Cell PD DEC PY 2014 VL 25 MA P2144 PG 2 WC Cell Biology SC Cell Biology GA CE8LP UT WOS:000352094105173 ER PT J AU Porter, JR Fisher, BE Batchelor, E AF Porter, J. R. Fisher, B. E. Batchelor, E. TI Multiplexed transcriptional analysis of p53 targets in single cells SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract CT ASCB/IFCB Meeting CY DEC 06-10, 2014 CL Philadelphia, PA SP Amer Soc Cell Biol, Int Federat Cell Biol C1 [Porter, J. R.; Fisher, B. E.; Batchelor, E.] NCI, Pathol Lab, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 EI 1939-4586 J9 MOL BIOL CELL JI Mol. Biol. Cell PD DEC PY 2014 VL 25 MA P2286 PG 2 WC Cell Biology SC Cell Biology GA CE8LP UT WOS:000352094105316 ER PT J AU Pronobis, M Rusan, NM Peifer, M AF Pronobis, M. Rusan, N. M. Peifer, M. TI Inside the destruction complex: APC's mechanistic role in downregulation of Wnt signaling. SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract CT ASCB/IFCB Meeting CY DEC 06-10, 2014 CL Philadelphia, PA SP Amer Soc Cell Biol, Int Federat Cell Biol C1 [Pronobis, M.] UNC, GMB, Chapel Hill, NC USA. [Pronobis, M.] HHMI, Chevy Chase, MD USA. [Rusan, N. M.] NHLBI, Cell Biol & Physiol Ctr, NIH, Bethesda, MD 20892 USA. [Peifer, M.] Univ N Carolina, Dept Biol, Chapel Hill, NC USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 EI 1939-4586 J9 MOL BIOL CELL JI Mol. Biol. Cell PD DEC PY 2014 VL 25 MA P1387 PG 1 WC Cell Biology SC Cell Biology GA CE8LP UT WOS:000352094103238 ER PT J AU Rambold, A Cohen, S Lippincott-Schwartz, J AF Rambold, A. Cohen, S. Lippincott-Schwartz, J. TI Regulated by mitochondrial fusion dynamics, lipid droplets serve as central fatty acid conduit to supply mitochondria with fatty acids for oxidation during nutrient stress SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract CT ASCB/IFCB Meeting CY DEC 06-10, 2014 CL Philadelphia, PA SP Amer Soc Cell Biol, Int Federat Cell Biol C1 [Rambold, A.] Max Planck Inst IE, Freiburg, Germany. [Cohen, S.; Lippincott-Schwartz, J.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Cell Biol & Metab Program, NIH, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 EI 1939-4586 J9 MOL BIOL CELL JI Mol. Biol. Cell PD DEC PY 2014 VL 25 MA P2123 PG 1 WC Cell Biology SC Cell Biology GA CE8LP UT WOS:000352094105152 ER PT J AU Remmert, K Beach, JR Porat-Shliom, N Weigert, R Yang, Y Sellers, JR Hammer, JA AF Remmert, K. Beach, J. R. Porat-Shliom, N. Weigert, R. Yang, Y. Sellers, J. R. Hammer, J. A. TI Myosin 18A localizes with myosin II at cell: cell junctions in epithelial cells and tissues. SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract CT ASCB/IFCB Meeting CY DEC 06-10, 2014 CL Philadelphia, PA SP Amer Soc Cell Biol, Int Federat Cell Biol C1 [Remmert, K.; Beach, J. R.; Hammer, J. A.] NHLBI, LCB, NIH, Bethesda, MD 20892 USA. [Porat-Shliom, N.; Weigert, R.] NIDCR, NIH, Bethesda, MD USA. [Yang, Y.] Hunan Agr Univ, Changsha, Hunan, Peoples R China. [Sellers, J. R.] NHLBI, LMP, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 EI 1939-4586 J9 MOL BIOL CELL JI Mol. Biol. Cell PD DEC PY 2014 VL 25 MA P108 PG 2 WC Cell Biology SC Cell Biology GA CE8LP UT WOS:000352094100109 ER PT J AU Reveal, B Lilly, M AF Reveal, B. Lilly, M. TI The role of the TORC1 regulator IML1 in meiotic progression and the response to cellular stress SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract CT ASCB/IFCB Meeting CY DEC 06-10, 2014 CL Philadelphia, PA SP Amer Soc Cell Biol, Int Federat Cell Biol C1 [Reveal, B.; Lilly, M.] NICHD, NIH, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 EI 1939-4586 J9 MOL BIOL CELL JI Mol. Biol. Cell PD DEC PY 2014 VL 25 MA P2324 PG 1 WC Cell Biology SC Cell Biology GA CE8LP UT WOS:000352094105354 ER PT J AU Ricca, BL Venugopalan, G Tanner, K Furata, S Orellana, W Reber, C Brownfield, DG Bissell, MJ Fletcher, DA AF Ricca, B. L. Venugopalan, G. Tanner, K. Furata, S. Orellana, W. Reber, C. Brownfield, D. G. Bissell, M. J. Fletcher, D. A. TI Transient external force induces phenotypic reversion of malignant epithelial structures via nitric oxide Signaling. SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract CT ASCB/IFCB Meeting CY DEC 06-10, 2014 CL Philadelphia, PA SP Amer Soc Cell Biol, Int Federat Cell Biol C1 [Ricca, B. L.; Venugopalan, G.; Reber, C.; Brownfield, D. G.; Fletcher, D. A.] Univ Calif Berkeley, Dept Bioengn, Berkeley, CA 94720 USA. [Tanner, K.; Furata, S.; Orellana, W.; Brownfield, D. G.; Bissell, M. J.] Univ Calif Berkeley, Lawrence Berkeley Natl Lab, Life Sci Div, Berkeley, CA 94720 USA. [Tanner, K.; Orellana, W.] NCI, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. [Brownfield, D. G.] Stanford Univ, Biochem, Stanford, CA 94305 USA. [Fletcher, D. A.] Univ Calif Berkeley, Biophys Grad Grp, Berkeley, CA 94720 USA. [Fletcher, D. A.] Univ Calif Berkeley, Lawrence Berkeley Natl Lab, Phys Biosci Div, Berkeley, CA 94720 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 EI 1939-4586 J9 MOL BIOL CELL JI Mol. Biol. Cell PD DEC PY 2014 VL 25 MA P1915 PG 1 WC Cell Biology SC Cell Biology GA CE8LP UT WOS:000352094104362 ER PT J AU Ritter, AT Betzig, E Griffiths, GM Lippincott-Schwartz, J AF Ritter, A. T. Betzig, E. Griffiths, G. M. Lippincott-Schwartz, J. TI Dynamic modulation of cortical actin at the immunological synapse controls cytotoxic granule secretion. SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract CT Joint Annual Meeting of the American-Society-for-Cell-Biology (ASCB) / International-Federation-for-Cell-Biology (IFCB) CY DEC 06-10, 2014 CL Philadelphia, PA SP Amer Soc Cell Biol, Int Federat Cell Biol C1 [Ritter, A. T.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Cell Biol & Metab Program, NIH, Bethesda, MD 20892 USA. [Ritter, A. T.] Univ Cambridge, Cambridge Inst Med Res, Cambridge, England. [Betzig, E.] HHMI Janelia Farm Res Campus, Ashburn, VA USA. [Griffiths, G. M.] Univ Cambridge, Cambridge, England. 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M.; Toro, C.; Introne, W. J.; Huizing, M.; Gahl, W. A.; Cullinane, A. R.] NHGRI, Med Genet Branch, NIH, Bethesda, MD 20892 USA. [Gul, D.] Gulhane Mil Med Acad, Dept Med Genet, Ankara, Turkey. [Mullikin, J. C.] NHGRI, Comparat Genom Anal Unit, Canc Genet & Comparat Genom Branch, NIH, Bethesda, MD 20892 USA. [Mullikin, J. C.] NIH Intramural Sequencing Ctr, NHGRI, NIH, Rockville, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 2 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 EI 1939-4586 J9 MOL BIOL CELL JI Mol. Biol. Cell PD DEC PY 2014 VL 25 MA P398 PG 1 WC Cell Biology SC Cell Biology GA CE8LP UT WOS:000352094101028 ER PT J AU Ryoo, M Harding, O Tangrea, MA Weigert, R Shitara, A Hanson, JC Rosenberg, A Porat-Shliom, N Chen, Y AF Ryoo, M. Harding, O. Tangrea, M. A. Weigert, R. Shitara, A. Hanson, J. C. Rosenberg, A. Porat-Shliom, N. Chen, Y. TI Developing Mitochondrial Enrichment for Targeted Analysis (META) to Study Phosphorylation Kinetics SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract CT ASCB/IFCB Meeting CY DEC 06-10, 2014 CL Philadelphia, PA SP Amer Soc Cell Biol, Int Federat Cell Biol C1 [Ryoo, M.; Tangrea, M. A.; Hanson, J. C.; Rosenberg, A.; Chen, Y.] NCI, NIH, Bethesda, MD 20892 USA. [Ryoo, M.] Duke Univ, Durham, NC USA. [Harding, O.; Weigert, R.; Shitara, A.; Porat-Shliom, N.] NIDCR, NIH, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 EI 1939-4586 J9 MOL BIOL CELL JI Mol. Biol. Cell PD DEC PY 2014 VL 25 MA P1605 PG 1 WC Cell Biology SC Cell Biology GA CE8LP UT WOS:000352094104070 ER PT J AU Satpute-Krishnan, P Lippincott-Schwartz, J AF Satpute-Krishnan, P. Lippincott-Schwartz, J. TI Quality control of GPI-anchored proteins in the secretory pathway. SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract CT Joint Annual Meeting of the American-Society-for-Cell-Biology (ASCB) / International-Federation-for-Cell-Biology (IFCB) CY DEC 06-10, 2014 CL Philadelphia, PA SP Amer Soc Cell Biol, Int Federat Cell Biol C1 [Satpute-Krishnan, P.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Cell Biol & Metab Program, NIH, Bethesda, MD USA. [Lippincott-Schwartz, J.] Marine Biol Lab, Physiol Course, Woods Hole, MA 02543 USA. [Lippincott-Schwartz, J.] NICHD, Cell Biol & Metab Program, NIH, Bethesda, MD USA. NR 2 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 EI 1939-4586 J9 MOL BIOL CELL JI Mol. Biol. Cell PD DEC PY 2014 VL 25 MA P650 PG 2 WC Cell Biology SC Cell Biology GA CE8LP UT WOS:000352094101278 ER PT J AU Schoborg, T Guillen, RX Rusan, NM AF Schoborg, T. Guillen, R. X. Rusan, N. M. TI Calmodulin and Abnormal Spindle Cooperate to Maintain Mitotic/Meiotic Spindle Integrity in D. melanogaster SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract CT ASCB/IFCB Meeting CY DEC 06-10, 2014 CL Philadelphia, PA SP Amer Soc Cell Biol, Int Federat Cell Biol C1 [Schoborg, T.; Rusan, N. M.] NHLBI, Cell Biol & Physiol Ctr, NIH, Bethesda, MD 20892 USA. [Guillen, R. X.] NHLBI, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 2 U2 3 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 EI 1939-4586 J9 MOL BIOL CELL JI Mol. Biol. Cell PD DEC PY 2014 VL 25 MA P1805 PG 1 WC Cell Biology SC Cell Biology GA CE8LP UT WOS:000352094104270 ER PT J AU Sengupta, P van Engelenburg, S Johnson, M Lippincott-Schwartz, J AF Sengupta, P. van Engelenburg, S. Johnson, M. Lippincott-Schwartz, J. TI Mechanism of protein incorporation into envelop of budding HIV particle. SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract CT Joint Annual Meeting of the American-Society-for-Cell-Biology (ASCB) / International-Federation-for-Cell-Biology (IFCB) CY DEC 06-10, 2014 CL Philadelphia, PA SP Amer Soc Cell Biol, Int Federat Cell Biol C1 [Sengupta, P.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Cell Biol & Metab Program, NIH, Bethesda, MD USA. [van Engelenburg, S.; Lippincott-Schwartz, J.] Marine Biol Lab, Physiol Course, Woods Hole, MA 02543 USA. [van Engelenburg, S.; Lippincott-Schwartz, J.] NICHD, Cell Biol & Metab Program, NIH, Bethesda, MD USA. [Johnson, M.] Univ Missouri, Columbia, MO USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 EI 1939-4586 J9 MOL BIOL CELL JI Mol. Biol. Cell PD DEC PY 2014 VL 25 MA M46 PG 1 WC Cell Biology SC Cell Biology GA CE8LP UT WOS:000352094106095 ER PT J AU Sheldon, KL Bezrukov, SM Sackett, DL AF Sheldon, K. L. Bezrukov, S. M. Sackett, D. L. TI Not just charged strings: binding of Tubulin's disordered tails to VDAC is regulated by small sequence changes and by posttranlational modification. SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract CT ASCB/IFCB Meeting CY DEC 06-10, 2014 CL Philadelphia, PA SP Amer Soc Cell Biol, Int Federat Cell Biol C1 [Sheldon, K. L.; Bezrukov, S. M.; Sackett, D. L.] NICHD, Program Phys Biol, NIH, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 1 U2 2 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 EI 1939-4586 J9 MOL BIOL CELL JI Mol. Biol. Cell PD DEC PY 2014 VL 25 MA P134 PG 2 WC Cell Biology SC Cell Biology GA CE8LP UT WOS:000352094100135 ER PT J AU Shomron, O Nevo-Yassaf, I Aviad, T Patterson, GH Hirschberg, K AF Shomron, O. Nevo-Yassaf, I. Aviad, T. Patterson, G. H. Hirschberg, K. TI Live cell microscopy of early ER export events underpins a new model for COPII function at the ER-ER exit site boundary. SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract CT ASCB/IFCB Meeting CY DEC 06-10, 2014 CL Philadelphia, PA SP Amer Soc Cell Biol, Int Federat Cell Biol C1 [Shomron, O.; Nevo-Yassaf, I.; Aviad, T.; Hirschberg, K.] Tel Aviv Univ, Pathol, IL-69978 Tel Aviv, Israel. [Patterson, G. H.] NIBIB, NIH, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 EI 1939-4586 J9 MOL BIOL CELL JI Mol. Biol. Cell PD DEC PY 2014 VL 25 MA P416 PG 2 WC Cell Biology SC Cell Biology GA CE8LP UT WOS:000352094101046 ER PT J AU Shu, S Liu, X Yu, S Lee, D Wang, G Gucek, M Korn, ED AF Shu, S. Liu, X. Yu, S. Lee, D. Wang, G. Gucek, M. Korn, E. D. TI Biochemical and Biological Properties of Dictyostelium Cortexillin III and Its Complex(es) with DGAP1. SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract CT ASCB/IFCB Meeting CY DEC 06-10, 2014 CL Philadelphia, PA SP Amer Soc Cell Biol, Int Federat Cell Biol C1 [Shu, S.; Liu, X.; Yu, S.; Lee, D.; Wang, G.; Gucek, M.; Korn, E. D.] NHLBI, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 EI 1939-4586 J9 MOL BIOL CELL JI Mol. Biol. Cell PD DEC PY 2014 VL 25 MA P899 PG 1 WC Cell Biology SC Cell Biology GA CE8LP UT WOS:000352094102145 ER PT J AU Shukla, AK Kong, D Sharma, M Loncarek, J AF Shukla, A. K. Kong, D. Sharma, M. Loncarek, J. TI Loss of block-to-centriole reduplication without a loss of centriole orthogonal orientation in human cells. SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract CT ASCB/IFCB Meeting CY DEC 06-10, 2014 CL Philadelphia, PA SP Amer Soc Cell Biol, Int Federat Cell Biol C1 [Shukla, A. K.; Kong, D.; Sharma, M.; Loncarek, J.] NCI, NIH, Lab Prot Dynam & Signaling, Frederick, MD 21701 USA. RI Kong, Dong/O-4465-2016 OI Kong, Dong/0000-0002-7144-3808 NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 EI 1939-4586 J9 MOL BIOL CELL JI Mol. Biol. Cell PD DEC PY 2014 VL 25 MA P1021 PG 1 WC Cell Biology SC Cell Biology GA CE8LP UT WOS:000352094102266 ER PT J AU Skau, CT Waterman, C AF Skau, C. T. Waterman, C. TI A novel actin-adhesion structure involved in nuclear positioning requires the formin FMN2. SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract CT ASCB/IFCB Meeting CY DEC 06-10, 2014 CL Philadelphia, PA SP Amer Soc Cell Biol, Int Federat Cell Biol C1 [Skau, C. T.; Waterman, C.] NHLBI, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 EI 1939-4586 J9 MOL BIOL CELL JI Mol. Biol. Cell PD DEC PY 2014 VL 25 MA P1649 PG 2 WC Cell Biology SC Cell Biology GA CE8LP UT WOS:000352094104114 ER PT J AU Skau, CT Plotnikov, SV Waterman, C AF Skau, C. T. Plotnikov, S. V. Waterman, C. TI The formin INF2 is a focal adhesion protein that promotes dorsal stress fiber and fibrillar adhesion formation to drive extracellular matrix assembly. SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract CT ASCB/IFCB Meeting CY DEC 06-10, 2014 CL Philadelphia, PA SP Amer Soc Cell Biol, Int Federat Cell Biol C1 [Skau, C. T.; Plotnikov, S. V.; Waterman, C.] NHLBI, NIH, Bethesda, MD 20892 USA. [Plotnikov, S. V.] Univ Toronto, Cell & Syst Biol, Toronto, ON, Canada. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 EI 1939-4586 J9 MOL BIOL CELL JI Mol. Biol. Cell PD DEC PY 2014 VL 25 MA P903 PG 1 WC Cell Biology SC Cell Biology GA CE8LP UT WOS:000352094102149 ER PT J AU Smith, GH AF Smith, G. H. TI Paracrine rescued lobulogenesis in PR null mammary outgrowths by redirected testicular cells SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract CT ASCB/IFCB Meeting CY DEC 06-10, 2014 CL Philadelphia, PA SP Amer Soc Cell Biol, Int Federat Cell Biol C1 [Smith, G. H.] NCI, BRL, NIH, CCR, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 EI 1939-4586 J9 MOL BIOL CELL JI Mol. Biol. Cell PD DEC PY 2014 VL 25 MA P2351 PG 2 WC Cell Biology SC Cell Biology GA CE8LP UT WOS:000352094105380 ER PT J AU Sochacki, KA Taraska, JW AF Sochacki, K. A. Taraska, J. W. TI A nanometer-scale survey of the structure and organization of clathrin-mediated endocytosis among mammalian cell lines SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract CT ASCB/IFCB Meeting CY DEC 06-10, 2014 CL Philadelphia, PA SP Amer Soc Cell Biol, Int Federat Cell Biol C1 [Sochacki, K. A.; Taraska, J. W.] NHLBI, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 EI 1939-4586 J9 MOL BIOL CELL JI Mol. Biol. Cell PD DEC PY 2014 VL 25 MA P1192 PG 2 WC Cell Biology SC Cell Biology GA CE8LP UT WOS:000352094103043 ER PT J AU Sun, L Vergarajauregui, S Puertollano, R AF Sun, L. Vergarajauregui, S. Puertollano, R. TI Inducible expression of MCOLN2 in immune cells SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract CT ASCB/IFCB Meeting CY DEC 06-10, 2014 CL Philadelphia, PA SP Amer Soc Cell Biol, Int Federat Cell Biol C1 [Sun, L.; Vergarajauregui, S.; Puertollano, R.] NHLBI, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 EI 1939-4586 J9 MOL BIOL CELL JI Mol. Biol. Cell PD DEC PY 2014 VL 25 MA P1216 PG 1 WC Cell Biology SC Cell Biology GA CE8LP UT WOS:000352094103067 ER PT J AU Sundborger, AC Hinshaw, JE AF Sundborger, A. C. Hinshaw, J. E. TI Super-constriction precedes GTP-hydrolysis dependent conformational changes in dynamin polymers during plasma membrane fission SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract CT ASCB/IFCB Meeting CY DEC 06-10, 2014 CL Philadelphia, PA SP Amer Soc Cell Biol, Int Federat Cell Biol C1 [Sundborger, A. C.; Hinshaw, J. E.] NIDDK, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 EI 1939-4586 J9 MOL BIOL CELL JI Mol. Biol. Cell PD DEC PY 2014 VL 25 MA P833 PG 1 WC Cell Biology SC Cell Biology GA CE8LP UT WOS:000352094102079 ER PT J AU Swaminathan, V Waterman, C AF Swaminathan, V. Waterman, C. TI Focal adhesion kinase links lamellipodial actin and nascent adhesions to the ECM through the Arp2/3 complex to regulate leading edge dynamics. SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract CT ASCB/IFCB Meeting CY DEC 06-10, 2014 CL Philadelphia, PA SP Amer Soc Cell Biol, Int Federat Cell Biol C1 [Swaminathan, V.] NHLBI, Cell Biol & Physiol Ctr, NIH, Bethesda, MD 20892 USA. [Waterman, C.] NHLBI, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 EI 1939-4586 J9 MOL BIOL CELL JI Mol. Biol. Cell PD DEC PY 2014 VL 25 MA P2226 PG 2 WC Cell Biology SC Cell Biology GA CE8LP UT WOS:000352094105256 ER PT J AU Szyk, A Deaconescu, A Spector, J Valenstein, M Goodman, B Kormendi, V Grigorieff, N Roll-Mecak, A AF Szyk, A. Deaconescu, A. Spector, J. Valenstein, M. Goodman, B. Kormendi, V. Grigorieff, N. Roll-Mecak, A. TI Generating the chemical complexity of tubulin: insights into the mechanism of tubulin post-translational modification enzymes SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract CT ASCB/IFCB Meeting CY DEC 06-10, 2014 CL Philadelphia, PA SP Amer Soc Cell Biol, Int Federat Cell Biol C1 [Szyk, A.; Spector, J.; Valenstein, M.; Goodman, B.; Kormendi, V.; Roll-Mecak, A.] NINDS, Cell Biol & Biophys, NIH, Bethesda, MD 20892 USA. 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NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 EI 1939-4586 J9 MOL BIOL CELL JI Mol. Biol. Cell PD DEC PY 2014 VL 25 MA P2241 PG 1 WC Cell Biology SC Cell Biology GA CE8LP UT WOS:000352094105271 ER PT J AU Traver, MK Paul, S Losert, W Shroff, H Schaefer, BC AF Traver, M. K. Paul, S. Losert, W. Shroff, H. Schaefer, B. C. TI Regulation of T cell receptor signaling to NF-kappa B by microtubule transport of signalosomes. SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract CT ASCB/IFCB Meeting CY DEC 06-10, 2014 CL Philadelphia, PA SP Amer Soc Cell Biol, Int Federat Cell Biol C1 [Traver, M. K.; Schaefer, B. C.] Uniformed Serv Univ Hlth Sci, Microbiol & Immunol, Bethesda, MD USA. [Paul, S.] Univ Toledo, Dept Internal Med, Med Ctr, Toledo, OH 43606 USA. [Losert, W.] Univ Maryland, Dept Phys, College Pk, MD 20742 USA. [Shroff, H.] NIBIB, Sect High Resolut Opt Imaging, NIH, Bethesda, MD USA. RI Shroff, Hari/E-7247-2016 OI Shroff, Hari/0000-0003-3613-8215 NR 0 TC 0 Z9 0 U1 0 U2 2 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 EI 1939-4586 J9 MOL BIOL CELL JI Mol. Biol. Cell PD DEC PY 2014 VL 25 MA M41 PG 2 WC Cell Biology SC Cell Biology GA CE8LP UT WOS:000352094106090 ER PT J AU Trexler, AJ Taraska, JW AF Trexler, A. J. Taraska, J. W. TI Investigating the regulation of pulmonary surfactant secretion using fluorescence microscopy. SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract CT ASCB/IFCB Meeting CY DEC 06-10, 2014 CL Philadelphia, PA SP Amer Soc Cell Biol, Int Federat Cell Biol C1 [Trexler, A. J.; Taraska, J. W.] NHLBI, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 EI 1939-4586 J9 MOL BIOL CELL JI Mol. Biol. Cell PD DEC PY 2014 VL 25 MA P1991 PG 2 WC Cell Biology SC Cell Biology GA CE8LP UT WOS:000352094105020 ER PT J AU Tsai, SA Pokrass, MJ Su, T AF Tsai, S. A. Pokrass, M. J. Su, T. TI Sigma-1 Receptor Deficiency Hinders p35 Degradation and Causes Impaired Neuronal Circuitry. SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract CT ASCB/IFCB Meeting CY DEC 06-10, 2014 CL Philadelphia, PA SP Amer Soc Cell Biol, Int Federat Cell Biol C1 [Tsai, S. A.; Pokrass, M. J.; Su, T.] NIDA, NIH, Baltimore, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 EI 1939-4586 J9 MOL BIOL CELL JI Mol. Biol. Cell PD DEC PY 2014 VL 25 MA P1502 PG 1 WC Cell Biology SC Cell Biology GA CE8LP UT WOS:000352094103353 ER PT J AU Valm, AM Cohen, S Legant, WR Davidson, MW Betzig, E Lippincott-Schwartz, J AF Valm, A. M. Cohen, S. Legant, W. R. Davidson, M. W. Betzig, E. Lippincott-Schwartz, J. TI Novel spectral imaging and analysis to unravel the organelle interactome SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract CT Joint Annual Meeting of the American-Society-for-Cell-Biology (ASCB) / International-Federation-for-Cell-Biology (IFCB) CY DEC 06-10, 2014 CL Philadelphia, PA SP Amer Soc Cell Biol, Int Federat Cell Biol C1 [Valm, A. M.; Cohen, S.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Cell Biol & Metab Program, NIH, Bethesda, MD USA. [Legant, W. R.; Betzig, E.] HHMI Janelia Farm Res Campus, Ashburn, VA USA. [Davidson, M. W.] Florida State Univ, Natl High Magnet Field Lab, Tallahassee, FL 32306 USA. [Davidson, M. W.] Florida State Univ, Dept Biol Sci, Tallahassee, FL 32306 USA. [Lippincott-Schwartz, J.] Marine Biol Lab, Physiol Course, Woods Hole, MA 02543 USA. [Lippincott-Schwartz, J.] NICHD, Cell Biol & Metab Program, NIH, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 EI 1939-4586 J9 MOL BIOL CELL JI Mol. Biol. Cell PD DEC PY 2014 VL 25 MA P1600 PG 2 WC Cell Biology SC Cell Biology GA CE8LP UT WOS:000352094104065 ER PT J AU Vural, A Al-Khodor, S Cheung, GY Shi, CS Srinivasan, L Briken, V Otto, M Fraser, ID Kehrl, JH AF Vural, A. Al-Khodor, S. Cheung, G. Y. Shi, C. S. Srinivasan, L. Briken, V. Otto, M. Fraser, I. D. Kehrl, J. H. TI Activator of G-protein Signaling 3 (AGS3)-induced lysosomal biogenesis mediates resistance against (antibiotic-resistant) intracellular pathogens. SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract CT ASCB/IFCB Meeting CY DEC 06-10, 2014 CL Philadelphia, PA SP Amer Soc Cell Biol, Int Federat Cell Biol C1 [Vural, A.; Shi, C. S.; Kehrl, J. H.] NIAID, Immunoregulat Lab, Bethesda, MD 20892 USA. [Al-Khodor, S.; Fraser, I. D.] NIAID, Lab Syst Biol, Bethesda, MD 20892 USA. [Cheung, G. 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RI Lu, Quanlong/M-4436-2015 OI Lu, Quanlong/0000-0002-4261-5121 NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 EI 1939-4586 J9 MOL BIOL CELL JI Mol. Biol. Cell PD DEC PY 2014 VL 25 MA P991 PG 1 WC Cell Biology SC Cell Biology GA CE8LP UT WOS:000352094102236 ER PT J AU Waterman, C Case, L Swaminathan, VS Skau, CT AF Waterman, C. Case, L. Swaminathan, V. S. Skau, C. T. TI Functional specificity of integrin-based adhesions in cell function is defined by actin nucleators. SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract CT ASCB/IFCB Meeting CY DEC 06-10, 2014 CL Philadelphia, PA SP Amer Soc Cell Biol, Int Federat Cell Biol C1 [Waterman, C.; Case, L.; Swaminathan, V. S.; Skau, C. T.] NHLBI, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 EI 1939-4586 J9 MOL BIOL CELL JI Mol. 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NR 0 TC 0 Z9 0 U1 1 U2 1 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 EI 1939-4586 J9 MOL BIOL CELL JI Mol. Biol. Cell PD DEC PY 2014 VL 25 MA P588 PG 2 WC Cell Biology SC Cell Biology GA CE8LP UT WOS:000352094101216 ER PT J AU Webster, MR Xu, M Kinzler, KA Kaur, A Appleton, J O'Connell, MP Marchbank, K Valiga, A Dang, VM Perego, M Zang, G Slipicevic, A Keeney, F Lehrmann, E Wood, W Becker, K Kossenkov, A Frederick, D Flaherty, K Xu, X Herlyn, M Murphy, ME Weeraratna, AT AF Webster, M. R. Xu, M. Kinzler, K. A. Kaur, A. Appleton, J. O'Connell, M. P. Marchbank, K. Valiga, A. Dang, V. M. Perego, M. Zang, G. Slipicevic, A. Keeney, F. Lehrmann, E. Wood, W., III Becker, K. Kossenkov, A. Frederick, D. Flaherty, K. Xu, X. Herlyn, M. Murphy, M. E. Weeraratna, A. T. TI Wnt5A promotes an adaptive, senescent-like stress response, while continuing to drive invasion in melanoma cells SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract CT ASCB/IFCB Meeting CY DEC 06-10, 2014 CL Philadelphia, PA SP Amer Soc Cell Biol, Int Federat Cell Biol C1 [Webster, M. R.; Kaur, A.; Appleton, J.; O'Connell, M. P.; Marchbank, K.; Valiga, A.; Dang, V. M.; Perego, M.; Zang, G.; Slipicevic, A.; Herlyn, M.; Weeraratna, A. T.] Wistar Inst Anat & Biol, Tumor Microenvironm & Metastasis, Philadelphia, PA 19104 USA. [Xu, M.; Kinzler, K. A.; Lehrmann, E.; Wood, W., III; Becker, K.] NIA, Baltimore, MD 21224 USA. [Keeney, F.] Wistar Inst Anat & Biol, Microscopy, Philadelphia, PA 19104 USA. [Kossenkov, A.] Wistar Inst Anat & Biol, Bioinformat, Philadelphia, PA 19104 USA. [Frederick, D.; Flaherty, K.] Massachusetts Gen Hosp, Ctr Canc, Boston, MA USA. [Xu, X.] Univ Penn, Abramson Canc Ctr, Philadelphia, PA 19104 USA. [Murphy, M. E.] Wistar Inst Anat & Biol, Mol & Cellular Oncogenesis, Philadelphia, PA 19104 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 EI 1939-4586 J9 MOL BIOL CELL JI Mol. Biol. Cell PD DEC PY 2014 VL 25 MA P1878 PG 2 WC Cell Biology SC Cell Biology GA CE8LP UT WOS:000352094104325 ER PT J AU Wei, Y Lilly, M AF Wei, Y. Lilly, M. TI The Drosophila SEA/GATOR complex controls meiotic progression and the response to amino acid starvation by modulating TORC1 activity SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract CT ASCB/IFCB Meeting CY DEC 06-10, 2014 CL Philadelphia, PA SP Amer Soc Cell Biol, Int Federat Cell Biol C1 [Wei, Y.] NICHD, NIH, Rockville, MD USA. [Lilly, M.] NICHD, NIH, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 EI 1939-4586 J9 MOL BIOL CELL JI Mol. Biol. Cell PD DEC PY 2014 VL 25 MA P2326 PG 1 WC Cell Biology SC Cell Biology GA CE8LP UT WOS:000352094105356 ER PT J AU Williams, C Liu, Y O'Connell, KF AF Williams, C. Liu, Y. O'Connell, K. F. TI A novel function for CDK--11 in fertilization and fecundity in C. elegans SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract CT ASCB/IFCB Meeting CY DEC 06-10, 2014 CL Philadelphia, PA SP Amer Soc Cell Biol, Int Federat Cell Biol C1 [Williams, C.; Liu, Y.; O'Connell, K. F.] NIDDK, Lab Biochem & Genet, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 EI 1939-4586 J9 MOL BIOL CELL JI Mol. Biol. Cell PD DEC PY 2014 VL 25 MA P2321 PG 1 WC Cell Biology SC Cell Biology GA CE8LP UT WOS:000352094105351 ER PT J AU Williamson, CD Donaldson, JG AF Williamson, C. D. Donaldson, J. G. TI Macropinocytosis as a model for tracking clathrin-independent cargo sorting in space and time. SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract CT ASCB/IFCB Meeting CY DEC 06-10, 2014 CL Philadelphia, PA SP Amer Soc Cell Biol, Int Federat Cell Biol C1 [Williamson, C. D.; Donaldson, J. G.] NHLBI, Cell Biol & Physiol Ctr, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 1 U2 2 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 EI 1939-4586 J9 MOL BIOL CELL JI Mol. Biol. Cell PD DEC PY 2014 VL 25 MA P378 PG 2 WC Cell Biology SC Cell Biology GA CE8LP UT WOS:000352094101008 ER PT J AU Wu, X Hammer, JA AF Wu, X. Hammer, J. A. TI Melanoregulin may influence melanosome distribution through its effects on the organization of lipids in the melanosome membrane. SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract CT ASCB/IFCB Meeting CY DEC 06-10, 2014 CL Philadelphia, PA SP Amer Soc Cell Biol, Int Federat Cell Biol C1 [Wu, X.] NHLBI, NIH, Bethesda, MD 20892 USA. [Hammer, J. A.] NHLBI, LCB, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 EI 1939-4586 J9 MOL BIOL CELL JI Mol. Biol. Cell PD DEC PY 2014 VL 25 MA P395 PG 2 WC Cell Biology SC Cell Biology GA CE8LP UT WOS:000352094101025 ER PT J AU Wu, Z Plotnikov, SV Waterman, C Liu, J AF Wu, Z. Plotnikov, S. V. Waterman, C. Liu, J. TI Two distinct actin networks mediate traction oscillations to confer mechanosensitivity of focal adhesions. SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract CT ASCB/IFCB Meeting CY DEC 06-10, 2014 CL Philadelphia, PA SP Amer Soc Cell Biol, Int Federat Cell Biol C1 [Wu, Z.; Plotnikov, S. V.; Waterman, C.; Liu, J.] Natl Inst Hlth, Natl Heart Lung & Blood Inst, Bethesda, MD USA. [Plotnikov, S. V.] Univ Toronto, Cell & Syst Biol, Toronto, ON, Canada. NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 EI 1939-4586 J9 MOL BIOL CELL JI Mol. Biol. Cell PD DEC PY 2014 VL 25 MA P1470 PG 2 WC Cell Biology SC Cell Biology GA CE8LP UT WOS:000352094103321 ER PT J AU Yamashita, RA Marchler-Bauer, A Bryant, S AF Yamashita, R. A. Marchler-Bauer, A. Bryant, S. TI Myosin Superfamily Classification using the Conserved Domain Database (CDD) Resource at NCBI SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract CT ASCB/IFCB Meeting CY DEC 06-10, 2014 CL Philadelphia, PA SP Amer Soc Cell Biol, Int Federat Cell Biol C1 [Yamashita, R. A.; Marchler-Bauer, A.; Bryant, S.] NCBI, NIH, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 EI 1939-4586 J9 MOL BIOL CELL JI Mol. Biol. Cell PD DEC PY 2014 VL 25 MA P937 PG 1 WC Cell Biology SC Cell Biology GA CE8LP UT WOS:000352094102182 ER PT J AU Yasui, Y Su, T AF Yasui, Y. Su, T. TI PCAF is involved in acetylation and subcellular distribution of Sigma-1 receptors. SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract CT ASCB/IFCB Meeting CY DEC 06-10, 2014 CL Philadelphia, PA SP Amer Soc Cell Biol, Int Federat Cell Biol C1 [Yasui, Y.; Su, T.] NIDA, NIH, Baltimore, MD USA. NR 0 TC 0 Z9 0 U1 2 U2 2 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 EI 1939-4586 J9 MOL BIOL CELL JI Mol. Biol. Cell PD DEC PY 2014 VL 25 MA P426 PG 2 WC Cell Biology SC Cell Biology GA CE8LP UT WOS:000352094101056 ER PT J AU Youle, RJ AF Youle, R. J. TI Damage control: how PINK1 and Parkin survey mitochondrial fidelity and respond with selective autophagy SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract CT ASCB/IFCB Meeting CY DEC 06-10, 2014 CL Philadelphia, PA SP Amer Soc Cell Biol, Int Federat Cell Biol C1 [Youle, R. J.] NINDS, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 EI 1939-4586 J9 MOL BIOL CELL JI Mol. Biol. Cell PD DEC PY 2014 VL 25 MA S13 PG 1 WC Cell Biology SC Cell Biology GA CE8LP UT WOS:000352094106236 ER PT J AU Young, LE Gauvin, TJ Heimsath, EG Higgs, H AF Young, L. E. Gauvin, T. J. Heimsath, E. G. Higgs, H. TI Arp2/3 complex-dependent assembly of filopodia by the formin FMNL3 contributes to cell-cell adhesion. SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract CT ASCB/IFCB Meeting CY DEC 06-10, 2014 CL Philadelphia, PA SP Amer Soc Cell Biol, Int Federat Cell Biol C1 [Young, L. E.] Dartmouth Coll, Hanover, NH 03755 USA. [Gauvin, T. J.] Dartmouth Geisel Sch Med, Hanover, NH USA. [Heimsath, E. G.] NIDCD, NIH, Bethesda, MD USA. [Higgs, H.] Dartmouth Coll, Geisel Sch Med, Dept Biochem, Hanover, NH 03755 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 EI 1939-4586 J9 MOL BIOL CELL JI Mol. Biol. Cell PD DEC PY 2014 VL 25 MA P1671 PG 2 WC Cell Biology SC Cell Biology GA CE8LP UT WOS:000352094104136 ER PT J AU Zhang, F Colavita, K Rodionova, I Buckley, B Scott, D Kumar, A Shabalina, S Saha, S Chernov, M Osterman, A Kashina, AS AF Zhang, F. Colavita, K. Rodionova, I. Buckley, B. Scott, D. Kumar, A. Shabalina, S. Saha, S. Chernov, M. Osterman, A. Kashina, A. S. TI Arginylation Regulates Purine Biosynthesis by Facilitating the Biological Activity of Phosphorybosyl Pyrophospate Synthase. SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract CT ASCB/IFCB Meeting CY DEC 06-10, 2014 CL Philadelphia, PA SP Amer Soc Cell Biol, Int Federat Cell Biol C1 [Zhang, F.; Kumar, A.] Univ Miami, Sch Med, Miami, FL USA. [Colavita, K.] Univ Penn, Philadelphia, PA 19104 USA. [Rodionova, I.] Sanford Burham Med Res Inst, La Jolla, CA USA. [Buckley, B.] Roswell Pk Canc Res Ctr, Buffalo, NY USA. [Scott, D.; Osterman, A.] 3Sanford Burnham Med Res Inst, La Jolla, CA USA. [Shabalina, S.] NCBI, NIH, Bethesda, MD USA. [Saha, S.] Tezpur Univ, Napaam, India. [Chernov, M.] Roswell Pk Canc Inst, Buffalo, NY 14263 USA. [Kashina, A. S.] Univ Penn, Sch Vet Med, Dept Anim Biol, Philadelphia, PA 19104 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 EI 1939-4586 J9 MOL BIOL CELL JI Mol. Biol. Cell PD DEC PY 2014 VL 25 MA P514 PG 2 WC Cell Biology SC Cell Biology GA CE8LP UT WOS:000352094101143 ER PT J AU Zhang, M Arnaoutov, A Dasso, M AF Zhang, M. Arnaoutov, A. Dasso, M. TI RanBP1 governs spindle assembly by defining mitotic Ran-GTP production. SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract CT ASCB/IFCB Meeting CY DEC 06-10, 2014 CL Philadelphia, PA SP Amer Soc Cell Biol, Int Federat Cell Biol C1 [Zhang, M.; Arnaoutov, A.; Dasso, M.] NICHHD, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 EI 1939-4586 J9 MOL BIOL CELL JI Mol. Biol. Cell PD DEC PY 2014 VL 25 MA P181 PG 2 WC Cell Biology SC Cell Biology GA CE8LP UT WOS:000352094100182 ER PT J AU Said, M AF Said, Maria TI In Liberia, the End of the Ebola Epidemic will be the Beginning SO ECOHEALTH LA English DT Editorial Material C1 [Said, Maria] US PHS, LCDR, Washington, DC 20201 USA. [Said, Maria] NIH, Div Int Training & Res, Fogarty Int Ctr, Rockville, MD 20852 USA. [Said, Maria] US FDA, Div Epidemiol, Off Biostat & Epidemiol, Ctr Biol Evaluat & Res, Silver Spring, MD 20993 USA. RP Said, M (reprint author), US PHS, LCDR, Washington, DC 20201 USA. EM said.maria@gmail.com NR 1 TC 0 Z9 0 U1 1 U2 3 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1612-9202 EI 1612-9210 J9 ECOHEALTH JI EcoHealth PD DEC PY 2014 VL 11 IS 4 BP 459 EP 460 DI 10.1007/s10393-015-1017-4 PG 2 WC Biodiversity Conservation; Ecology; Environmental Sciences SC Biodiversity & Conservation; Environmental Sciences & Ecology GA CE5HB UT WOS:000351860800003 PM 25691142 ER PT J AU Perrings, C Castillo-Chavez, C Chowell, G Daszak, P Fenichel, EP Finnoff, D Horan, RD Kilpatrick, AM Kinzig, AP Kuminoff, NV Levin, S Morin, B Smith, KF Springborn, M AF Perrings, Charles Castillo-Chavez, Carlos Chowell, Gerardo Daszak, Peter Fenichel, Eli P. Finnoff, David Horan, Richard D. Kilpatrick, A. Marm Kinzig, Ann P. Kuminoff, Nicolai V. Levin, Simon Morin, Benjamin Smith, Katherine F. Springborn, Michael TI Merging Economics and Epidemiology to Improve the Prediction and Management of Infectious Disease SO ECOHEALTH LA English DT Article DE economic epidemiology; epidemiological economics; incentives; infectious disease ID PANDEMIC INFLUENZA; WILDLIFE DISEASE; UNITED-KINGDOM; REPRODUCTION NUMBER; MATHEMATICAL-MODELS; COST-EFFECTIVENESS; AVIAN INFLUENZA; HUMAN-BEHAVIOR; SPREAD; TRADE AB Mathematical epidemiology, one of the oldest and richest areas in mathematical biology, has significantly enhanced our understanding of how pathogens emerge, evolve, and spread. Classical epidemiological models, the standard for predicting and managing the spread of infectious disease, assume that contacts between susceptible and infectious individuals depend on their relative frequency in the population. The behavioral factors that underpin contact rates are not generally addressed. There is, however, an emerging a class of models that addresses the feedbacks between infectious disease dynamics and the behavioral decisions driving host contact. Referred to as "economic epidemiology" or "epidemiological economics," the approach explores the determinants of decisions about the number and type of contacts made by individuals, using insights and methods from economics. We show how the approach has the potential both to improve predictions of the course of infectious disease, and to support development of novel approaches to infectious disease management. C1 [Perrings, Charles; Kinzig, Ann P.; Morin, Benjamin] Arizona State Univ, Sch Life Sci, Tempe, AZ 85287 USA. [Castillo-Chavez, Carlos] Arizona State Univ, Math Computat & Modeling Sci Ctr, Tempe, AZ 85287 USA. [Castillo-Chavez, Carlos; Chowell, Gerardo] Arizona State Univ, Sch Human Evolut & Social Change, Tempe, AZ 85287 USA. [Chowell, Gerardo] NIH, Div Epidemiol & Populat Studies, Fogarty Int Ctr, Bethesda, MD 20892 USA. [Daszak, Peter] EcoHlth Alliance, New York, NY 10001 USA. [Fenichel, Eli P.] Yale Univ, Sch Forestry & Environm Studies, New Haven, CT 06511 USA. [Finnoff, David] Univ Wyoming, Dept Econ & Finance, Laramie, WY 82071 USA. [Horan, Richard D.] Michigan State Univ, Dept Agr Food & Resource Econ, E Lansing, MI 48824 USA. [Kilpatrick, A. Marm] Univ Calif Santa Cruz, Dept Ecol & Evolutionary Biol, Santa Cruz, CA 95064 USA. [Kuminoff, Nicolai V.] Arizona State Univ, Dept Econ, Tempe, AZ 85287 USA. [Levin, Simon] Princeton Univ, Dept Ecol & Evolutionary Biol, Princeton, NJ 08544 USA. [Smith, Katherine F.] Brown Univ, Dept Ecol & Evolutionary Biol, Providence, RI 02912 USA. [Springborn, Michael] Univ Calif Davis, Dept Environm Sci & Policy, Davis, CA 95616 USA. RP Perrings, C (reprint author), Arizona State Univ, Sch Life Sci, Tempe, AZ 85287 USA. EM charles.perrings@asu.edu; ccchavez@asu.edu; gchowell@asu.edu; daszak@ecohealthalliance.org; eli.fenichel@yale.edu; finnoff@uwyo.edu; horan@msu.edu; akilpatr@ucsc.edu; kinzig@asu.edu; kuminoff@asu.edu; slevin@princeton.edu; brmorin@asu.edu; katherine_smith@brown.edu; mspringborn@ucdavis.edu OI Fenichel, Eli/0000-0002-7649-8250; Castillo-Chavez, Carlos/0000-0002-1046-3901 FU National Institute of General Medical Sciences (NIGMS) at the National Institutes of Health [1R01GM100471-01]; USDA National Institute of Food and Agriculture [2011-67023-30872]; NSF [81140 - 443559]; American people through the United States Agency for International Development (USAID) Emerging Pandemic Threats PREDICT FX This publication was made possible by grant #1R01GM100471-01 from the National Institute of General Medical Sciences (NIGMS) at the National Institutes of Health. In addition, Rick Horan acknowledges funding from the USDA National Institute of Food and Agriculture, grant #2011-67023-30872. Marm Kilpatrick acknowledges NSF grant #81140 - 443559. Peter Daszak acknowledges the generous support of the American people through the United States Agency for International Development (USAID) Emerging Pandemic Threats PREDICT. NR 131 TC 11 Z9 11 U1 6 U2 33 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1612-9202 EI 1612-9210 J9 ECOHEALTH JI EcoHealth PD DEC PY 2014 VL 11 IS 4 BP 464 EP 475 DI 10.1007/s10393-014-0963-6 PG 12 WC Biodiversity Conservation; Ecology; Environmental Sciences SC Biodiversity & Conservation; Environmental Sciences & Ecology GA CE5HB UT WOS:000351860800005 PM 25233829 ER PT J AU Dunleavy, K AF Dunleavy, Kieron TI Double-hit lymphomas: current paradigms and novel treatment approaches SO HEMATOLOGY-AMERICAN SOCIETY OF HEMATOLOGY EDUCATION PROGRAM LA English DT Article ID B-CELL LYMPHOMA; RITUXIMAB PLUS CYCLOPHOSPHAMIDE; BURKITT-LYMPHOMA; GERMINAL CENTER; MOLECULAR SUBTYPES; ANTITUMOR-ACTIVITY; PREDICTS SURVIVAL; GENE-EXPRESSION; POOR-PROGNOSIS; PHASE-II AB Double-hit lymphomas (DHLs) are a heterogeneous group of mature B-cell lymphomas that harbor concurrent rearrangements of MYC and BCL2 or, occasionally, BCL6. Several studies have now shown that they are associated with a very aggressive clinical course and poor outcome after standard R-CHOP (cyclophosphamide, doxorubicin, vincristine, and prednisone) therapy, with few patients surviving beyond 2 years. Due to their rarity, there is a paucity of data evaluating patient outcomes with alternative strategies to R-CHOP and no consensus on how they should be optimally managed. Recent studies have demonstrated that a significant proportion of diffuse large B-cell lymphoma (DLBCL) cases have high protein expression of MYC and BCL2 as detected by IHC. These so-called "double-expressor" DLBCLs are also associated with a poor outcome after R-CHOP, even when MYC and BCL2 rearrangements are absent. There is much interest in developing new strategies for DHL and better characterizing the underlying biology that drives their poor prognosis. Alternative chemotherapy platforms to R-CHOP, such as DA-EPOCH-R (dose-adjusted etoposide, prednisone, vincristine, cyclophosphamide, doxorubicin and rituximab), are under investigation for MYC-rearranged DLBCL, including DHL, and several novel small-molecule inhibitors of MYC and BCL2 are in development. C1 [Dunleavy, Kieron] NCI, Lymphoid Malignancies Branch, Ctr Canc Res, Bethesda, MD 20892 USA. RP Dunleavy, K (reprint author), NCI, Lymphoid Malignancies Branch, 9000 Rockville Pike,Bldg 10,Room 4N-115, Bethesda, MD 20892 USA. EM dunleavk@mail.nih.gov FU intramural program of the National Cancer Institute FX This work was supported by the intramural program of the National Cancer Institute. NR 45 TC 0 Z9 1 U1 2 U2 8 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 2021 L ST NW, SUITE 900, WASHINGTON, DC 20036 USA SN 1520-4391 EI 1520-4383 J9 HEMATOL-AM SOC HEMAT JI Hematol.-Am. Soc. Hematol. Educ. Program PD DEC PY 2014 BP 107 EP 112 DI 10.1182/asheducation-2014.1.107 PG 6 WC Education, Scientific Disciplines; Hematology SC Education & Educational Research; Hematology GA CC9XN UT WOS:000350724600015 ER PT J AU Wiestner, A AF Wiestner, Adrian TI BCR pathway inhibition as therapy for chronic lymphocytic leukemia and lymphoplasmacytic lymphoma SO HEMATOLOGY-AMERICAN SOCIETY OF HEMATOLOGY EDUCATION PROGRAM LA English DT Article ID B-CELL-RECEPTOR; TYROSINE KINASE INHIBITOR; L265P SOMATIC MUTATION; NON-HODGKIN-LYMPHOMA; WALDENSTROM MACROGLOBULINEMIA; TUMOR PROLIFERATION; PHOSPHATIDYLINOSITOL 3-KINASE-DELTA; ANTIGEN RECEPTORS; T-LYMPHOCYTES; TARGETING BTK AB Chronic lymphocytic leukemia (CLL) and lymphoplasmacytic lymphoma (LPL) are malignancies of mature B cells. In LPL, mutations of the adaptor protein MYD88 (L265P) in the Toll-like receptor pathway have been recognized recently as being a hallmark of the disease and indicate a dependence of the tumor on this pathway. In CLL, functional studies have implicated BCR activation in the tissue microenvironment as a pivotal pathway in the pathogenesis. Bruton's tyrosine kinase (BTK) and the PI3K delta isoform are essential for BCR signaling and also seem to be required for signal transduction in LPL cells, even if the role of BCR signaling in this disease remains less well defined. Ibrutinib, a covalent inhibitor of BTK approved by the Food and Drug Administration as a second-line treatment for CLL, and idelalisib, a selective inhibitor of PI3K delta, achieve excellent clinical responses in both diseases irrespective of classic markers indicating high-risk disease. Several additional inhibitors targeting BTK and PI3K delta, as well as the spleen tyrosine kinase, have entered clinical trials. This review discusses the biologic basis for kinase inhibitors as targeted therapy for CLL and LPL and summarizes the clinical experience with these agents. C1 NHLBI, Hematol Branch, NIH, Bethesda, MD 20892 USA. RP Wiestner, A (reprint author), NHLBI, Hematol Branch, NIH, Bldg 10,CRC 3-5140,10 Ctr Dr, Bethesda, MD 20892 USA. EM wiestnea@nhlbi.nih.gov FU National Heart, Lung, and Blood Institute of the National Institutes of Health FX The author is supported by the intramural research program of the National Heart, Lung, and Blood Institute of the National Institutes of Health. NR 107 TC 1 Z9 1 U1 0 U2 4 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 2021 L ST NW, SUITE 900, WASHINGTON, DC 20036 USA SN 1520-4391 EI 1520-4383 J9 HEMATOL-AM SOC HEMAT JI Hematol.-Am. Soc. Hematol. Educ. Program PD DEC PY 2014 BP 125 EP 134 DI 10.1182/asheducation-2014.1.125 PG 10 WC Education, Scientific Disciplines; Hematology SC Education & Educational Research; Hematology GA CC9XN UT WOS:000350724600018 ER PT J AU Bollard, CM Barrett, AJ AF Bollard, Catherine M. Barrett, A. John TI Cytotoxic T lymphocytes for leukemia and lymphoma SO HEMATOLOGY-AMERICAN SOCIETY OF HEMATOLOGY EDUCATION PROGRAM LA English DT Article ID EPSTEIN-BARR-VIRUS; MINOR HISTOCOMPATIBILITY ANTIGENS; HODGKIN-LYMPHOMA; CELL THERAPY; LYMPHOPROLIFERATIVE DISEASE; TRANSPLANT RECIPIENTS; COMPLETE RESPONSES; DONOR LYMPHOCYTES; IMMUNOTHERAPY; TUMORS AB This chapter focuses on the recent advances in adoptive T-cell immunotherapies, not only for patients after hematopoietic stem cell transplantation, but also in the autologous setting using T cells early in the disease process for the treatment of the highest-risk patients with leukemias and lymphomas. The particular emphasis is to highlight the role of T-cell therapies for hematologic malignancies using a non-gene-transfer approach to direct specificity, including the clinical use of T-cell therapies for EBV-associated lymphomas and strategies for targeting nonviral lymphoma-and leukemia-associated antigens. C1 [Bollard, Catherine M.] Childrens Natl Hlth Syst, Washington, DC 20010 USA. [Bollard, Catherine M.] George Washington Univ, Washington, DC USA. [Barrett, A. John] NHLBI, NIH, Bethesda, MD 20892 USA. RP Bollard, CM (reprint author), Childrens Natl Hlth Syst, 111 Michigan Ave NW, Washington, DC 20010 USA. EM cbollard@cnmc.org NR 37 TC 0 Z9 0 U1 1 U2 4 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 2021 L ST NW, SUITE 900, WASHINGTON, DC 20036 USA SN 1520-4391 EI 1520-4383 J9 HEMATOL-AM SOC HEMAT JI Hematol.-Am. Soc. Hematol. Educ. Program PD DEC PY 2014 BP 565 EP 569 DI 10.1182/asheducation-2014.1.565 PG 5 WC Education, Scientific Disciplines; Hematology SC Education & Educational Research; Hematology GA CC9XN UT WOS:000350724600085 ER PT J AU Zholdybayeva, EV Rakhimova, SE Baikara, BT Nigmatullina, NB Mustapayeva, NM Momynaliev, KT AF Zholdybayeva, Elena V. Rakhimova, Saule E. Baikara, Barshagul T. Nigmatullina, Nazym B. Mustapayeva, Nagima M. Momynaliev, Kuvat T. TI Alport syndrome in a Kazakh family: a case study SO JOURNAL OF GENETICS LA English DT Article DE Alport syndrome; COL4A5 gene; X-linked Alport syndrome ID COLLAGEN; IDENTIFICATION; MUTATIONS; GENES C1 [Zholdybayeva, Elena V.; Rakhimova, Saule E.; Baikara, Barshagul T.; Momynaliev, Kuvat T.] Natl Biotechnol Ctr, Astana 010000, Kazakhstan. [Nigmatullina, Nazym B.; Mustapayeva, Nagima M.] Natl Res Ctr Maternal & Child Hlth, Astana 010000, Kazakhstan. RP Zholdybayeva, EV (reprint author), Natl Biotechnol Ctr, 13-1 Valikhanov St, Astana 010000, Kazakhstan. EM lenazhol@gmail.com FU Ministry of Education and Science of the Republic of Kazakhstan FX We are grateful to the XLAS family for their participation in this study. This study was supported by Ministry of Education and Science of the Republic of Kazakhstan. NR 14 TC 0 Z9 0 U1 0 U2 3 PU INDIAN ACAD SCIENCES PI BANGALORE PA C V RAMAN AVENUE, SADASHIVANAGAR, P B #8005, BANGALORE 560 080, INDIA SN 0022-1333 EI 0973-7731 J9 J GENET JI J. Genet. PD DEC PY 2014 VL 93 IS 3 BP 855 EP 858 DI 10.1007/s12041-014-0448-y PG 4 WC Genetics & Heredity SC Genetics & Heredity GA CC4BZ UT WOS:000350297100030 PM 25572247 ER PT J AU Deveney, CM Brotman, MA Thomas, LA Hinton, KE Muhrer, EM Reynolds, RC Adleman, NE Zarate, CA Pine, DS Leibenluft, E AF Deveney, Christen M. Brotman, Melissa A. Thomas, Laura A. Hinton, Kendra E. Muhrer, Eli M. Reynolds, Richard C. Adleman, Nancy E. Zarate, Carlos A., Jr. Pine, Daniel S. Leibenluft, Ellen TI Neural response during explicit and implicit face processing varies developmentally in bipolar disorder SO SOCIAL COGNITIVE AND AFFECTIVE NEUROSCIENCE LA English DT Article ID MAJOR DEPRESSIVE DISORDER; SEVERE MOOD DYSREGULATION; FACIAL EXPRESSIONS; ANTERIOR CINGULATE; AMYGDALA ACTIVATION; LABELING DEFICITS; EMOTIONAL FACES; NEUTRAL FACES; CHILDREN; CIRCUITRY AB Both children and adults with bipolar disorder (BD) exhibit face emotion labeling deficits and neural circuitry dysfunction in response to emotional faces. However, few studies have compared these groups directly to distinguish effects of age and diagnosis. Such studies are important to begin to elucidate the developmental trajectory of BD and facilitate its diagnosis, prevention and treatment. This functional magnetic resonance imaging study compares 41 individuals with BD (19 children; 22 adults) and 44 age-matched healthy individuals (25 children; 19 adults) when making explicit or implicit judgments about angry or happy face morphs across a range of emotion intensity. Linear trend analyses revealed that BD patients, irrespective of age, failed to recruit the amygdala in response to increasing angry face. This finding was no longer significant when the group was restricted to euthymic youth or those without comorbid attention deficit hyperactivity disorder although this may reflect low statistical power. Deficits in subgenual anterior cingulate modulation were observed in both patient groups but were related to implicit processing for child patients and explicit processing for adult patients. Abnormalities in face emotion labeling and the circuitry mediating it may be biomarkers of BD that are present across development. C1 [Deveney, Christen M.; Brotman, Melissa A.; Thomas, Laura A.; Hinton, Kendra E.; Muhrer, Eli M.; Adleman, Nancy E.; Pine, Daniel S.; Leibenluft, Ellen] NIMH, Emot & Dev Branch, Dept Hlth & Human Serv, NIH, Bethesda, MD 20892 USA. [Zarate, Carlos A., Jr.] NIMH, Sect Neurobiol & Treatment Mood Disorders, Dept Hlth & Human Serv, NIH, Bethesda, MD 20892 USA. [Reynolds, Richard C.] NIMH, Sci & Stat Comp Core, Dept Hlth & Human Serv, NIH, Bethesda, MD 20892 USA. RP Deveney, CM (reprint author), Wellesley Coll, Dept Psychol, 106 Cent St, Wellesley, MA 02481 USA. EM cdeveney@wellesley.edu RI Brotman, Melissa/H-7409-2013; OI Thomas, Laura/0000-0002-4106-1358 FU Intramural Research Program at the National Institute of Mental Health, part of the National Institutes of Health [ZIA MH002786 12] FX This research was supported by the Intramural Research Program at the National Institute of Mental Health, part of the National Institutes of Health (ZIA MH002786 12). C.A.Z. is listed as a co-inventor on a patent application for the use of ketamine in major depression; he has assigned his rights in the patent to the US government but will share a percentage of any royalties that may be received by the government. All other authors report no financial relationships with commercial interests. The authors gratefully acknowledge the efforts of members of the Emotion and Development Branch, and the participation of the patients and families in their research endeavors. NR 52 TC 2 Z9 2 U1 5 U2 9 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 1749-5016 EI 1749-5024 J9 SOC COGN AFFECT NEUR JI Soc. Cogn. Affect. Neurosci. PD DEC PY 2014 VL 9 IS 12 BP 1984 EP 1992 DI 10.1093/scan/nsu014 PG 9 WC Neurosciences; Psychology; Psychology, Experimental SC Neurosciences & Neurology; Psychology GA CC1MU UT WOS:000350105900015 PM 24493839 ER PT J AU Sukal-Moulton, T de Campos, AC Stanley, CJ Damiano, DL AF Sukal-Moulton, Theresa de Campos, Ana Carolina Stanley, Christopher J. Damiano, Diane L. TI Functional Near Infrared Spectroscopy of the Sensory and Motor Brain Regions with Simultaneous Kinematic and EMG Monitoring During Motor Tasks SO JOVE-JOURNAL OF VISUALIZED EXPERIMENTS LA English DT Article DE Behavior; Issue 94; functional near infrared spectroscopy; fNIRS; brain activity; gait; motor tasks; cerebral palsy; coordination ID CEREBRAL-PALSY; CONGENITAL HEMIPARESIS; CHILDREN; REORGANIZATION; TREADMILL; SYSTEM; FNIRS; FMRI AB There are several advantages that functional near-infrared spectroscopy (fNIRS) presents in the study of the neural control of human movement. It is relatively flexible with respect to participant positioning and allows for some head movements during tasks. Additionally, it is inexpensive, light weight, and portable, with very few contraindications to its use. This presents a unique opportunity to study functional brain activity during motor tasks in individuals who are typically developing, as well as those with movement disorders, such as cerebral palsy. An additional consideration when studying movement disorders, however, is the quality of actual movements performed and the potential for additional, unintended movements. Therefore, concurrent monitoring of both blood flow changes in the brain and actual movements of the body during testing is required for appropriate interpretation of fNIRS results. Here, we show a protocol for the combination of fNIRS with muscle and kinematic monitoring during motor tasks. We explore gait, a unilateral multi-joint movement (cycling), and two unilateral single-joint movements (isolated ankle dorsiflexion, and isolated hand squeezing). The techniques presented can be useful in studying both typical and atypical motor control, and can be modified to investigate a broad range of tasks and scientific questions. C1 [Sukal-Moulton, Theresa; de Campos, Ana Carolina; Stanley, Christopher J.; Damiano, Diane L.] NIH, Funct & Appl Biomech Sect, Dept Rehabil Med, Ctr Clin, Bethesda, MD 20892 USA. RP Damiano, DL (reprint author), NIH, Funct & Appl Biomech Sect, Dept Rehabil Med, Ctr Clin, Bethesda, MD 20892 USA. EM damianod@cc.nih.gov FU Intramural Research Program at the National Institutes of Health Clinical Center FX This project was funded by the Intramural Research Program at the National Institutes of Health Clinical Center. We acknowledge the helpful discussions with Dr. Thomas Bulea, PhD and Laurie Ohlrich, PT in refining the procedures presented in this protocol. Muyinat W. Osoba and Andrew Gravunder, MS assisted with the animations. NR 26 TC 1 Z9 1 U1 2 U2 9 PU JOURNAL OF VISUALIZED EXPERIMENTS PI CAMBRIDGE PA 1 ALEWIFE CENTER, STE 200, CAMBRIDGE, MA 02140 USA SN 1940-087X J9 JOVE-J VIS EXP JI J. Vis. Exp. PD DEC PY 2014 IS 94 AR e52391 DI 10.3791/52391 PG 10 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA CB1AE UT WOS:000349358000069 ER PT J AU Baker, SG Prorok, PC Kramer, BS AF Baker, Stuart G. Prorok, Philip C. Kramer, Barnett S. TI Lead Time and Overdiagnosis SO JNCI-JOURNAL OF THE NATIONAL CANCER INSTITUTE LA English DT Editorial Material ID BREAST-CANCER; MORTALITY C1 [Baker, Stuart G.; Prorok, Philip C.; Kramer, Barnett S.] NCI, Canc Prevent Div, Bethesda, MD 20892 USA. RP Baker, SG (reprint author), NCI, 9609 Med Ctr Dr,5E638 MSC 9789, Bethesda, MD 20892 USA. EM sb16i@nih.gov NR 10 TC 7 Z9 7 U1 0 U2 1 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0027-8874 EI 1460-2105 J9 JNCI-J NATL CANCER I JI JNCI-J. Natl. Cancer Inst. PD DEC PY 2014 VL 106 IS 12 AR dju346 DI 10.1093/jnci/dju346 PG 3 WC Oncology SC Oncology GA CA0FU UT WOS:000348593200024 ER PT J AU Gu, FY Wacholder, S Freedman, ND Panagiotou, OA Reyes-Guzman, C Bertazzi, PA Caporaso, NE AF Gu, Fangyi Wacholder, Sholom Freedman, Neal D. Panagiotou, Orestis A. Reyes-Guzman, Carolyn Bertazzi, Pier Alberto Caporaso, Neil E. TI RE: Time to Smoke First Morning Cigarette (TTFC) and Lung Cancer in a Case-Control Study Response SO JNCI-JOURNAL OF THE NATIONAL CANCER INSTITUTE LA English DT Letter C1 NCI, Div Canc Epidemiol & Genet, NIH, Bethesda, MD 20850 USA. [Bertazzi, Pier Alberto] Univ Milan, Milan, Italy. RP Caporaso, NE (reprint author), NCI, Div Canc Epidemiol & Genet, Room 6E410,9609 Med Ctr Dr, Bethesda, MD 20850 USA. EM caporaso@nih.gov RI Freedman, Neal/B-9741-2015; Panagiotou, Orestis/I-5934-2015; bertazzi, pietro alberto/D-5039-2017 OI Freedman, Neal/0000-0003-0074-1098; Panagiotou, Orestis/0000-0001-9604-8380; bertazzi, pietro alberto/0000-0003-3475-2449 NR 8 TC 1 Z9 1 U1 2 U2 3 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 DEC PY 2014 VL 106 IS 12 AR dju350 DI 10.1093/jnci/dju350 PG 1 WC Oncology SC Oncology GA CA0FU UT WOS:000348593200026 ER PT J AU Renfro, LA Grothey, A Xue, Y Saltz, LB Andre, T Twelves, C Labianca, R Allegra, CJ Alberts, SR Loprinzi, CL Yothers, G Sargent, DJ AF Renfro, Lindsay A. Grothey, Axel Xue, Yuan Saltz, Leonard B. Andre, Thierry Twelves, Chris Labianca, Roberto Allegra, Carmen J. Alberts, Steven R. Loprinzi, Charles L. Yothers, Greg Sargent, Daniel J. CA Adjuvant Colon Canc Endpoints TI ACCENT-Based Web Calculators to Predict Recurrence and Overall Survival in Stage III Colon Cancer SO JNCI-JOURNAL OF THE NATIONAL CANCER INSTITUTE LA English DT Article ID ADJUVANT TREATMENT; PLUS OXALIPLATIN; TRIAL; FLUOROURACIL; THERAPY; BEVACIZUMAB; LEUCOVORIN; CARCINOMA AB Background Current prognostic tools in colon cancer use relatively few patient characteristics. We constructed and validated clinical calculators for overall survival (OS) and time to recurrence (TTR) for stage III colon cancer and compared their performance against an existing tool (Numeracy) and American Joint Committee on Cancer (AJCC) version 7 staging. Methods Data from 15 936 stage III patients accrued to phase III clinical trials since 1989 were used to construct Cox models for TTR and OS. Variables included age, sex, race, body mass index, performance status, tumor grade, tumor stage, ratio of positive lymph nodes to nodes examined, number and location of primary tumors, and adjuvant treatment (fluoropyrimidine single agent or in combination). Missing data were imputed, and final models internally validated for optimism-corrected calibration and discrimination and compared with AJCC. External validation and comparisons against Numeracy were performed using stage III patients from NSABP trial C-08. All statistical tests were two-sided. Results All variables were statistically and clinically significant for OS prediction, while age and race did not predict TTR. No meaningful interactions existed. Models for OS and TTR were well calibrated and associated with C-indices of 0.66 and 0.65, respectively, compared with C-indices of 0.58 and 0.59 for AJCC. These tools, available online, better predicted patient outcomes than Numeracy, both overall and within patient subgroups, in external validation. Conclusions The proposed ACCENT calculators are internally and externally valid, better discriminate patient risk than AJCC version 7 staging, and better predict patient outcomes than Numeracy. These tools have replaced Numeracy for online clinical use and will aid prognostication and patient/physician communication. C1 [Renfro, Lindsay A.; Sargent, Daniel J.] Mayo Clin, Div Biomed Stat & Informat, Rochester, MN 55905 USA. [Grothey, Axel; Alberts, Steven R.; Loprinzi, Charles L.] Mayo Clin, Dept Oncol, Rochester, MN 55905 USA. [Xue, Yuan] Univ Virginia, Dept Stat, Charlottesville, VA USA. [Saltz, Leonard B.] Mem Sloan Kettering Canc Ctr, Gastrointestinal Oncol Serv, New York, NY 10021 USA. [Andre, Thierry] Hop St Antoine, F-75571 Paris, France. [Andre, Thierry] Univ Paris 06, Paris, France. [Twelves, Chris] Univ Leeds, Leeds Inst Canc & Pathol, Leeds LS2 9JT, W Yorkshire, England. [Twelves, Chris] St James Univ Hosp, Leeds Canc Res UK Ctr, Leeds, W Yorkshire, England. [Labianca, Roberto] Osped Giovanni 23, Oncol Unit, Bergamo, Italy. [Allegra, Carmen J.] Univ Florida, Div Hematol & Oncol, Gainesville, FL USA. [Yothers, Greg] Natl Surg Adjuvant Breast & Bowel Project, Ctr Biostat, Pittsburgh, PA USA. RP Renfro, LA (reprint author), Mayo Clin, Harwick 8-43,200 First St SW, Rochester, MN 55905 USA. EM renfro.lindsay@mayo.edu RI Labianca, Roberto/N-1847-2016; OI Labianca, Roberto/0000-0001-7149-822X; Yothers, Greg/0000-0002-7965-7333; Saltz, Leonard/0000-0001-8353-4670 FU National Cancer Institute [CA 25224] FX Funding was provided by National Cancer Institute Grant CA 25224. NR 22 TC 4 Z9 4 U1 0 U2 1 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0027-8874 EI 1460-2105 J9 JNCI-J NATL CANCER I JI JNCI-J. Natl. Cancer Inst. PD DEC PY 2014 VL 106 IS 12 AR dju333 DI 10.1093/jnci/dju333 PG 9 WC Oncology SC Oncology GA CA0FU UT WOS:000348593200009 ER PT J AU Falorni, A Minarelli, V Eads, CM Joachim, CM Persani, L Rossetti, R Beim, PY Pellegrini, VA Schnatz, PF Rafique, S Kissell, K Calis, KA Popat, V Nelson, LM AF Falorni, A. Minarelli, V. Eads, C. M. Joachim, C. M. Persani, L. Rossetti, R. Beim, P. Yurttas Pellegrini, V. A. Schnatz, P. F. Rafique, S. Kissell, K. Calis, K. A. Popat, V. Nelson, L. M. TI A clinical research integration special program (CRISP) for young women with primary ovarian insufficiency SO PANMINERVA MEDICA LA English DT Article DE Autoimmune oophoritis; Community-based participatory research; Mobile health units; Menopause; premature; Primary ovarian insufficiency; Rare diseases ID RANDOMIZED-CONTROLLED-TRIAL; BONE-MINERAL DENSITY; AUTOIMMUNE POLYGLANDULAR SYNDROME; HORMONE REPLACEMENT THERAPY; IDIOPATHIC ADDISONS-DISEASE; FRAGILE-X-SYNDROME; POSTMENOPAUSAL WOMEN; ADRENAL INSUFFICIENCY; TURNER-SYNDROME; GONADOTROPIN RECEPTORS AB Large-scale medical sequencing provides a focal point around which to reorganize health care and health care research. Mobile health (mHealth) is also currently undergoing explosive growth and could be another innovation that will change the face of future health care. We are employing primary ovarian insufficiency (POI) as a model rare condition to explore the intersection of these potentials. As both sequencing capabilities and our ability to intepret this information improve, sequencing for medical purposes will play an increasing role in health care beyond basic research: it will help guide the delivery of care to patients. POI is a serious chronic disorder and syndrome characterized by hypergonadotrophic hypogonadism before the age of 40 years and most commonly presents with amenorrhea. It may have adverse health effects that become fully evident years after the initial diagnosis. The condition is most commonly viewed as one of infertility, however, it may also be associated with adverse long-term outcomes related to inadequate bone mineral density, increased risk of cardiovascular disease, adrenal insufficiency, hypothyroidism and, if pregnancy ensues, having a child with Fragile X Syndrome. There may also be adverse outcomes related to increased rates of anxiety and depression. POI is also a rare disease, and accordingly, presents special challenges. Too often advances in research are not effectively integrated into community care at the point of service for those with rare diseases. There is a need to connect community health providers in real time with investigators who have the requisite knowledge and expertise to help manage the rare disease and to conduct ongoing research. Here we review the pathophysiology and management of POI and propose the development of an international Clinical Research Integration Special Program (CRISP) for the condition. C1 [Falorni, A.; Minarelli, V.] Univ Perugia, Dept Med, I-06126 Perugia, Italy. [Eads, C. M.; Joachim, C. M.] Rachels Well, Mclean, VA USA. [Persani, L.; Rossetti, R.] Univ Milan, Dept Clin Sci & Community Hlth, Lab Endocrine & Metab Res, Milan, Italy. [Persani, L.; Rossetti, R.] IRCCS, Ist Auxologico Italiano, Div Endocrine & Metab Dis, Milan, Italy. [Beim, P. Yurttas] Celmatix Inc, New York, NY USA. [Pellegrini, V. A.; Schnatz, P. F.] Reading Hosp, Dept Obstet & Gynecol, Reading, PA USA. [Schnatz, P. F.] Reading Hosp, Dept Internal Med, Reading, PA USA. [Schnatz, P. F.] Thomas Jefferson Univ, Jefferson Med Coll, Dept Obstet & Gynecol, Philadelphia, PA 19107 USA. [Schnatz, P. F.] Thomas Jefferson Univ, Jefferson Med Coll, Dept Internal Med, Philadelphia, PA 19107 USA. [Schnatz, P. F.] FaithCare, Hartford, CT USA. [Rafique, S.; Kissell, K.; Calis, K. A.; Popat, V.; Nelson, L. M.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Intramural Res Program Reprod & Adult Endocrinol, NIH, Bethesda, MD USA. [Nelson, L. M.] US PHS, Rockville, MD USA. RP Falorni, A (reprint author), Univ Perugia, Dept Med, Via E Dal Pozzo, I-06126 Perugia, Italy. EM alberto.falorni@unipg.it OI Persani, Luca/0000-0003-2068-9581 FU EU FP7 [201167]; Euradrenal and Fondazione Cassa di Risparmio di Perugia; Mary Elizabeth Conover Foundation; Telethon Foundation, Italy [GGP09126A]; Intramural Research Program of the Eunice Kennedy Schriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, Maryland, USA FX The associated research activity has been supported by EU FP7, Grant number 201167, Euradrenal and Fondazione Cassa di Risparmio di Perugia (to AF), a grant from the Mary Elizabeth Conover Foundation (to CME), Telethon Foundation, Grant GGP09126A (to LP), Italy, and by the Intramural Research Program of the Eunice Kennedy Schriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, Maryland, USA. We thank Peter and Cindy Catches of Oceti Wakan (http://www.ocetiwakan.org) for valuable discussions and Mark Ferguson for valuable help in graphic design. NR 147 TC 1 Z9 1 U1 1 U2 9 PU EDIZIONI MINERVA MEDICA PI TURIN PA CORSO BRAMANTE 83-85 INT JOURNALS DEPT., 10126 TURIN, ITALY SN 0031-0808 EI 1827-1898 J9 PANMINERVA MED JI Panminerva Medica PD DEC PY 2014 VL 56 IS 4 BP 245 EP 261 PG 17 WC Medicine, General & Internal SC General & Internal Medicine GA CA9UK UT WOS:000349270100001 PM 25288327 ER PT J AU Jacobson, KA AF Jacobson, Kenneth A. TI Structure-based discovery of novel ligands of GPCRs: adenosine and P2Y receptors SO PURINERGIC SIGNALLING LA English DT Meeting Abstract C1 [Jacobson, Kenneth A.] NIDDK, Mol Recognit Sect, Bioorgan Chem Lab, NIH, Bethesda, MD 20892 USA. RI Jacobson, Kenneth/A-1530-2009 OI Jacobson, Kenneth/0000-0001-8104-1493 NR 7 TC 0 Z9 0 U1 1 U2 1 PU SPRINGER PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 1573-9538 EI 1573-9546 J9 PURINERG SIGNAL JI Purinergic Signal. PD DEC PY 2014 VL 10 IS 4 BP 658 EP 658 PG 1 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA CA0BF UT WOS:000348578700015 ER PT J AU Jacobson, KA Robaye, B Boeynaems, JM Balasubramanian, R AF Jacobson, Kenneth A. Robaye, Bernard Boeynaems, Jean-Marie Balasubramanian, Ramachandran TI Beneficial effects of P2Y(6) receptor agonists on insulin release and survival of pancreatic beta-islet cells and in target tissue: involvement of 5 '-AMP-activated protein kinase (AMPK) SO PURINERGIC SIGNALLING LA English DT Meeting Abstract C1 [Jacobson, Kenneth A.; Balasubramanian, Ramachandran] Natl Inst Diabet & Digest & Kidney Dis, Mol Recognit Sect, NIH, Bethesda, MD USA. [Robaye, Bernard] Univ Libre Bruxelles, IRIBHM, Inst Interdisciplinary Res, Gosselies, Belgium. [Boeynaems, Jean-Marie] Univ Libre Bruxelles, Brussels, Belgium. RI Jacobson, Kenneth/A-1530-2009 OI Jacobson, Kenneth/0000-0001-8104-1493 NR 1 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 1573-9538 EI 1573-9546 J9 PURINERG SIGNAL JI Purinergic Signal. PD DEC PY 2014 VL 10 IS 4 BP 668 EP 669 PG 2 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA CA0BF UT WOS:000348578700039 ER PT J AU Yang, TH Shen, JB Yang, RH Redden, J Dodge-Kafka, K Grady, J Jacobson, KA Liang, BT AF Yang, Tiehong Shen, Jian-Bing Yang, Ronghua Redden, John Dodge-Kafka, Kimberley Grady, James Jacobson, Kenneth A. Liang, Bruce T. TI Novel protective role of endogenous cardiac myocyte P2X4 receptors in heart failure SO PURINERGIC SIGNALLING LA English DT Meeting Abstract C1 [Yang, Tiehong; Shen, Jian-Bing; Yang, Ronghua; Redden, John; Dodge-Kafka, Kimberley; Grady, James; Liang, Bruce T.] Univ Connecticut, Sch Med, Farmington, CT USA. NIH, Bethesda, MD 20892 USA. RI Jacobson, Kenneth/A-1530-2009 OI Jacobson, Kenneth/0000-0001-8104-1493 NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 1573-9538 EI 1573-9546 J9 PURINERG SIGNAL JI Purinergic Signal. PD DEC PY 2014 VL 10 IS 4 BP 676 EP 676 PG 1 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA CA0BF UT WOS:000348578700062 ER PT J AU Kang, E Sharma, K Han, KL Malech, H AF Kang, Elizabeth Sharma, Karlie Han, Kyu Lee Malech, Harry TI Adenosine agonists for the management of graft versus host disease SO PURINERGIC SIGNALLING LA English DT Meeting Abstract C1 [Kang, Elizabeth; Sharma, Karlie; Han, Kyu Lee; Malech, Harry] NIAID, NIH, Bethesda, MD 20892 USA. NR 1 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 1573-9538 EI 1573-9546 J9 PURINERG SIGNAL JI Purinergic Signal. PD DEC PY 2014 VL 10 IS 4 BP 682 EP 682 PG 1 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA CA0BF UT WOS:000348578700077 ER PT J AU Zhao, Q Zhang, KH Zhang, J Gao, ZG Jiang, HL Mueller, CE Cherezov, V Katritch, V Stevens, R Jacobson, KA Wu, BL AF Zhao, Qiang Zhang, Kaihua Zhang, Jin Gao, Zhan-Guo Jiang, Hualiang Mueller, Christa E. Cherezov, Vadim Katritch, Vsevolod Stevens, Raymond Jacobson, Kenneth A. Wu, Beili TI Structure and functional implications of purinoceptor 12 SO PURINERGIC SIGNALLING LA English DT Meeting Abstract C1 [Zhao, Qiang; Zhang, Kaihua; Zhang, Jin; Jiang, Hualiang] Shanghai Inst Mat Med, Shanghai, Peoples R China. [Mueller, Christa E.] Univ Bonn, Pharma Ctr Bonn, Bonn, Germany. [Gao, Zhan-Guo; Jacobson, Kenneth A.] Natl Inst Diabet & Digest & Kidney Dis, Bethesda, MD USA. [Cherezov, Vadim; Katritch, Vsevolod; Stevens, Raymond] Scripps Res Inst, La Jolla, CA 92037 USA. RI Jacobson, Kenneth/A-1530-2009; Katritch, Vsevolod/Q-8357-2016 OI Jacobson, Kenneth/0000-0001-8104-1493; NR 0 TC 0 Z9 0 U1 0 U2 2 PU SPRINGER PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 1573-9538 EI 1573-9546 J9 PURINERG SIGNAL JI Purinergic Signal. PD DEC PY 2014 VL 10 IS 4 BP 689 EP 689 PG 1 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA CA0BF UT WOS:000348578700095 ER PT J AU Du, LL Gao, ZG Paoletta, S Wan, TN van Veldhoven, J IJzerman, A Jacobson, K Auchampach, J AF Du, Lili Gao, Zhan-Guo Paoletta, Silvia Wan, Tina van Veldhoven, Jacobus IJzerman, Adriaan Jacobson, Kenneth Auchampach, John TI Species differences and molecular mechanism of action of A(3) adenosine receptor allosteric modulators SO PURINERGIC SIGNALLING LA English DT Meeting Abstract C1 [Du, Lili; Wan, Tina; Auchampach, John] Med Coll Wisconsin, Milwaukee, WI 53226 USA. [Gao, Zhan-Guo; Paoletta, Silvia; Jacobson, Kenneth] NIH, Mol Recognit Sect, Bethesda, MD 20892 USA. [van Veldhoven, Jacobus; IJzerman, Adriaan] Leiden Univ, Div Med Chem, Leiden, Netherlands. NR 0 TC 0 Z9 0 U1 1 U2 1 PU SPRINGER PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 1573-9538 EI 1573-9546 J9 PURINERG SIGNAL JI Purinergic Signal. PD DEC PY 2014 VL 10 IS 4 MA C024 BP 755 EP 755 PG 1 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA CA0BF UT WOS:000348578700253 ER PT J AU Carlsson, J Rodriguez, D Ranganathan, A Moss, SM Gao, ZG Stoddart, LA Hill, SJ Jacobson, KA AF Carlsson, Jens Rodriguez, David Ranganathan, Anirudh Moss, Steven M. Gao, Zhan-Guo Stoddart, Leigh A. Hill, Stephen J. Jacobson, Kenneth A. TI Ligand discovery from adenosine receptor crystal structures and homology models SO PURINERGIC SIGNALLING LA English DT Meeting Abstract C1 [Carlsson, Jens; Rodriguez, David; Ranganathan, Anirudh] Stockholm Univ, S-10691 Stockholm, Sweden. [Moss, Steven M.; Gao, Zhan-Guo; Jacobson, Kenneth A.] NIDDK, NIH, Mol Recognit Sect, Bioorgan Chem Lab, Bethesda, MD 20892 USA. [Stoddart, Leigh A.; Hill, Stephen J.] Univ Nottingham, Inst Cell Signalling, Sch Biomed Sci, Nottingham NG7 2RD, England. RI Jacobson, Kenneth/A-1530-2009 OI Jacobson, Kenneth/0000-0001-8104-1493 NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 1573-9538 EI 1573-9546 J9 PURINERG SIGNAL JI Purinergic Signal. PD DEC PY 2014 VL 10 IS 4 MA D059 BP 771 EP 772 PG 2 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA CA0BF UT WOS:000348578700288 ER PT J AU Jacobson, KA Kiselev, E Jayasekara, PS Barrett, MO Katritch, V Paoletta, S Weitzer, C Hammes, E Balasubramanian, R Gao, ZG Zhao, Q Stevens, RC Harden, TK AF Jacobson, Kenneth A. Kiselev, Evgeny Jayasekara, P. Suresh Barrett, Matthew O. Katritch, Vsevolod Paoletta, Silvia Weitzer, Clarissa Hammes, Eva Balasubramanian, Ramachandran Gao, Zhan-Guo Zhao, Qiang Stevens, Raymond C. Harden, T. Kendall TI Design, synthesis and characterization of high affinity fluorescent agonist and antagonist ligands of G protein-coupled P2Y receptors SO PURINERGIC SIGNALLING LA English DT Meeting Abstract C1 [Jacobson, Kenneth A.; Kiselev, Evgeny; Jayasekara, P. Suresh; Paoletta, Silvia; Hammes, Eva; Balasubramanian, Ramachandran; Gao, Zhan-Guo] NIDDK, Mol Recognit Sect, Bioorgan Chem Lab, NIH, Bethesda, MD 20892 USA. [Barrett, Matthew O.; Weitzer, Clarissa; Harden, T. Kendall] Univ N Carolina, Sch Med, Dept Pharmacol, Chapel Hill, NC 27599 USA. [Zhao, Qiang] Chinese Acad Sci, Shanghai Inst Mat Med, CAS Key Lab Receptor Res, Shanghai 201203, Peoples R China. [Katritch, Vsevolod; Stevens, Raymond C.] Scripps Res Inst, Dept Integrat Struct & Computat Biol, La Jolla, CA 92037 USA. RI Jacobson, Kenneth/A-1530-2009; Katritch, Vsevolod/Q-8357-2016 OI Jacobson, Kenneth/0000-0001-8104-1493; NR 1 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 1573-9538 EI 1573-9546 J9 PURINERG SIGNAL JI Purinergic Signal. PD DEC PY 2014 VL 10 IS 4 MA D074 BP 781 EP 781 PG 1 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA CA0BF UT WOS:000348578700303 ER PT J AU Trikalinos, TA Hoaglin, DC Small, KM Terrin, N Schmid, CH AF Trikalinos, Thomas A. Hoaglin, David C. Small, Kevin M. Terrin, Norma Schmid, Christopher H. TI Methods for the joint meta-analysis of multiple tests SO RESEARCH SYNTHESIS METHODS LA English DT Article DE joint meta-analysis; multinomial likelihood; multivariate normal; regularized regression; restricted maximum likelihood; Bayesian analysis ID SONOGRAPHIC SCORING INDEX; FEMUR LENGTH RATIO; DOWN-SYNDROME; CHROMOSOMAL-ABNORMALITIES; 2ND-TRIMESTER FETUSES; TRISOMY-21; ULTRASOUND; HUMERUS; RISK; IDENTIFICATION AB Existing methods for meta-analysis of diagnostic test accuracy focus primarily on a single index test. We propose models for the joint meta-analysis of studies comparing multiple index tests on the same participants in paired designs. These models respect the grouping of data by studies, account for the within-study correlation between the tests' true-positive rates (TPRs) and between their false-positive rates (FPRs) (induced because tests are applied to the same participants), and allow for between-study correlations between TPRs and FPRs (such as those induced by threshold effects). We estimate models in the Bayesian setting. We demonstrate using a meta-analysis of screening for Down syndrome with two tests: shortened humerus (arm bone), and shortened femur (thigh bone). Separate and joint meta-analyses yielded similar TPR and FPR estimates. For example, the summary TPR for a shortened humerus was 35.3% (95% credible interval (CrI): 26.9, 41.8%) versus 37.9% (27.7, 50.3%) with joint versus separate meta-analysis. Joint meta-analysis is more efficient when calculating comparative accuracy: the difference in the summary TPRs was 0.0% (-8.9, 9.5%; TPR higher for shortened humerus) with joint versus 2.6% (-14.7, 19.8%) with separate meta-analyses. Simulation and empirical analyses are needed to refine the role of the proposed methodology. Copyright (c) 2014 John Wiley & Sons, Ltd. C1 [Trikalinos, Thomas A.; Hoaglin, David C.; Schmid, Christopher H.] Brown Univ, Sch Publ Hlth, Ctr Evidence Based Med, Providence, RI 02912 USA. [Trikalinos, Thomas A.] Brown Univ, Sch Publ Hlth, Dept Hlth Serv Policy & Practice, Providence, RI 02912 USA. [Hoaglin, David C.] Univ Massachusetts, Sch Med, Dept Quantitat Hlth Sci, Worcester, MA USA. [Hoaglin, David C.] Consulting Statistician, Sudbury, ON, Canada. [Small, Kevin M.] NIH, Off Portfolio Anal, Bethesda, MD 20892 USA. [Terrin, Norma] Tufts Univ, Clin & Translat Sci Inst, Biostat Res Ctr, Res Design Ctr, Boston, MA 02111 USA. [Terrin, Norma] Tufts Med Ctr, Inst Clin Res & Hlth Policy Studies, Boston, MA USA. [Schmid, Christopher H.] Brown Univ, Sch Publ Hlth, Dept Biostat, Providence, RI 02912 USA. RP Trikalinos, TA (reprint author), Brown Univ, Ctr Evidence Based Med, 121 S Main St, Providence, RI 02912 USA. EM thomas_trikalinos@brown.edu OI Schmid, Christopher/0000-0002-0855-5313 FU Effective Healthcare Program of the Agency for Health Care Research and Quality (AHRQ) [HHSA 290 2007 10055 I]; AHRQ [R01HS018574] FX This manuscript is based on work performed under Contract No. HHSA 290 2007 10055 I to Tufts Medical Center in the context of the Effective Healthcare Program of the Agency for Health Care Research and Quality (AHRQ). The findings and conclusions expressed here are those of the authors and do not necessarily represent the views of AHRQ. Therefore, no statement should be construed as an official position of AHRQ or of the U.S. Department of Health and Human Services. Authors TT and CS were partly funded by grant R01HS018574 from AHRQ. NR 52 TC 1 Z9 1 U1 0 U2 2 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1759-2879 EI 1759-2887 J9 RES SYNTH METHODS JI Res. Synth. Methods PD DEC PY 2014 VL 5 IS 4 BP 294 EP 312 DI 10.1002/jrsm.1115 PG 19 WC Mathematical & Computational Biology; Multidisciplinary Sciences SC Mathematical & Computational Biology; Science & Technology - Other Topics GA CA6VH UT WOS:000349053400002 PM 26052954 ER PT J AU Kiselev, E Barrett, MO Katritch, V Paoletta, S Weitzer, CD Brown, KA Hammes, E Yin, AL Zhao, Q Stevens, RC Harden, TK Jacobson, KA AF Kiselev, Evgeny Barrett, Matthew O. Katritch, Vsevolod Paoletta, Silvia Weitzer, Clarissa D. Brown, Kyle A. Hammes, Eva Yin, Andrew L. Zhao, Qiang Stevens, Raymond C. Harden, T. Kendall Jacobson, Kenneth A. TI Exploring a 2-Naphthoic Acid Template for the Structure-Based Design of P2Y(14) Receptor Antagonist Molecular Probes SO ACS CHEMICAL BIOLOGY LA English DT Article ID HUMAN NEUTROPHILS; DERIVATIVES; AGONISTS; CHEMOTAXIS; ALKYLATION; MECHANISM; ANALOGS; SCOPE; DRUG AB The P2Y(14) receptor (P2Y(14)R), one of eight P2Y G protein-coupled receptors (GPCR), is involved in inflammatory, endocrine, and hypoxic processes and is an attractive pharmaceutical target. The goal of this research is to develop high-affinity P2Y(14)R fluorescent probes based on the potent and highly selective antagonist 4-(4-(piperidin-4-yl)-phenyl)-7-(4-(trifluoromethyl)-phenyl)-2-naphthoic acid (6, PPTN). A model of hP2Y(14)R based on recent hP2Y(12)R X-ray structures together with simulated antagonist docking suggested that the piperidine ring is suitable for fluorophore conjugation while preserving affinity. Chain-elongated alkynyl or amino derivatives of 6 for click or amide coupling were synthesized, and their antagonist activities were measured in hP2Y(14)R-expressing CHO cells. Moreover, a new Alexa Fluor 488 (AF488) containing derivative 30 (MRS4174, K-i = 80 pM) exhibited exceptionally high affinity, as compared to 13 nM for the alkyne precursor 22. A flow cytometry assay employing 30 as a fluorescent probe was used to quantify specific binding to P2Y(14)R. Known P2Y receptor ligands inhibited binding of 30 with properties consistent with their previously established receptor selectivities and affinities. These results illustrate that potency in this series of 2-naphthoic acid derivatives can be preserved by chain functionalization, leading to highly potent fluorescent molecular probes for P2Y(14)R. Such conjugates will be useful tools in expanding the SAR of this receptor, which still lacks chemical diversity in its collective ligands. This approach demonstrates the predictive power of GPCR homology modeling and the relevance of newly determined X-ray structures to GPCR medicinal chemistry. C1 [Kiselev, Evgeny; Paoletta, Silvia; Hammes, Eva; Yin, Andrew L.; Jacobson, Kenneth A.] NIDDK, Mol Recognit Sect, Bioorgan Chem Lab, NIH, Bethesda, MD 20892 USA. [Barrett, Matthew O.; Weitzer, Clarissa D.; Brown, Kyle A.; Harden, T. Kendall] Univ N Carolina, Sch Med, Dept Pharmacol, Chapel Hill, NC 27599 USA. [Zhao, Qiang] Chinese Acad Sci, Shanghai Inst Mat Med, CAS Key Lab Receptor Res, Shanghai 201203, Peoples R China. [Katritch, Vsevolod; Stevens, Raymond C.] Scripps Res Inst, Dept Integrat Struct & Computat Biol, La Jolla, CA 92037 USA. RP Jacobson, KA (reprint author), NIDDK, Mol Recognit Sect, Bioorgan Chem Lab, NIH, Bethesda, MD 20892 USA. EM kajacobs@helix.nih.gov RI Jacobson, Kenneth/A-1530-2009; Katritch, Vsevolod/Q-8357-2016; Stevens, Raymond/K-7272-2015 OI Jacobson, Kenneth/0000-0001-8104-1493; Stevens, Raymond/0000-0002-4522-8725 FU NIGMS Postdoctoral Research Associate (PRAT) Program; Intramural Program of the National Institute of Diabetes and Digestive and Kidney Diseases; National Institutes of Health [GM38213, U54GM094618] FX Mass spectral measurements were carried out by J. Lloyd and N. Whittaker (NIDDK). We acknowledge support from the NIGMS Postdoctoral Research Associate (PRAT) Program and the Intramural Program of the National Institute of Diabetes and Digestive and Kidney Diseases. This work was supported by National Institutes of Health grant nos. GM38213 to T.K.H. and U54GM094618 to V.K. and R.C.S. NR 40 TC 10 Z9 10 U1 3 U2 8 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 1554-8929 EI 1554-8937 J9 ACS CHEM BIOL JI ACS Chem. Biol. PD DEC PY 2014 VL 9 IS 12 BP 2833 EP 2842 DI 10.1021/cb500614p PG 10 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA AX2FS UT WOS:000346759600017 PM 25299434 ER PT J AU Xu, J Zhou, JY Xu, ZF Kho, DH Zhuang, ZP Raz, A Wu, GS AF Xu, Jing Zhou, Jun-Ying Xu, Zhengfan Kho, Dhong-Hyo Zhuang, Zhengping Raz, Avraham Wu, Gen Sheng TI The role of Cullin3-mediated ubiquitination of the catalytic subunit of PP2A in TRAIL signaling SO CELL CYCLE LA English DT Article DE apoptosis resistance; Cullin3; PP2A; TRAIL; ubiquitination ID PROTEIN PHOSPHATASE 2A; INDUCED APOPTOSIS; DEATH RECEPTORS; CANCER CELLS; PHASE-I; LIGASES; INHIBITION; FAMILY; LIGAND; IDENTIFICATION AB Protein phosphatase 2A (PP2A) is the major serine-threonine phosphatase that regulates a number of cell signaling pathways. PP2A activity is controlled partially through protein degradation; however, the underlying mechanism is not fully understood. Here we show that PP2A/C, a catalytic subunit of PP2A, is degraded by the Cullin3 (Cul3) ligase-mediated ubiquitin-proteasome pathway. In response to death receptor signaling by tumor-necrosis factor-related apoptosis-inducing ligand (TRAIL), PP2A/C, caspase-8 and Cul3, a subunit of the cullin family of E3 ligases, are recruited into the death-inducing signaling complex (DISC) where the Cul3 ligase targets PP2A/C for ubiquitination and subsequent degradation. Functionally, knockdown of PP2A/C expression by siRNA or pharmacological inhibition of PP2A activity increases TRAIL-induced apoptosis. In cancer cells that have developed acquired TRAIL resistance, PP2A phosphatase activity is increased, and PP2A/C protein is resistant to TRAIL-induced degradation. Thus, this work identifies a new mechanism by which PP2A/C is regulated by Cul3 ligase-mediated degradation in response to death receptor signaling and suggests that inhibition of PP2A/C degradation may contribute to resistance of cancer cells to death receptor-induced apoptosis. C1 [Xu, Jing; Zhou, Jun-Ying; Xu, Zhengfan; Kho, Dhong-Hyo; Raz, Avraham; Wu, Gen Sheng] Wayne State Univ, Sch Med, Karmanos Canc Inst, Dept Oncol, Detroit, MI 48202 USA. [Xu, Jing; Zhou, Jun-Ying; Xu, Zhengfan; Kho, Dhong-Hyo; Raz, Avraham; Wu, Gen Sheng] Wayne State Univ, Sch Med, Dept Pathol, Karmanos Canc Inst, Detroit, MI 48201 USA. [Zhuang, Zhengping] NINDS, Surg Neurol Branch, NIH, Bethesda, MD 20892 USA. RP Wu, GS (reprint author), Wayne State Univ, Sch Med, Karmanos Canc Inst, Dept Oncol, Detroit, MI 48202 USA. EM wug@karmanos.org FU NIH/NCI [R01CA174949-01A1] FX This work was supported in part by NIH/NCI R01CA174949-01A1. NR 40 TC 4 Z9 4 U1 0 U2 1 PU LANDES BIOSCIENCE PI AUSTIN PA 1806 RIO GRANDE ST, AUSTIN, TX 78702 USA SN 1538-4101 EI 1551-4005 J9 CELL CYCLE JI Cell Cycle PD DEC 1 PY 2014 VL 13 IS 23 BP 3750 EP 3758 DI 10.4161/15384101.2014.965068 PG 9 WC Cell Biology SC Cell Biology GA AZ6KQ UT WOS:000348329200017 PM 25551360 ER PT J AU Onoye, JMM Hishinuma, ES McArdle, JJ Zonderman, AB Bumanglag, RJ Takeshita, J AF Onoye, Jane M. M. Hishinuma, Earl S. McArdle, John J. Zonderman, Alan B. Bumanglag, R. Janine Takeshita, Junji TI Cohort Profile: The Hawai'i Family Study of Cognition SO INTERNATIONAL JOURNAL OF EPIDEMIOLOGY LA English DT Article DE Cognition; family; longitudinal studies; ethnic groups ID JAPANESE-AMERICAN MEN; 2 ETHNIC-GROUPS; PARENT-OFFSPRING RESEMBLANCE; OCCUPATIONAL ATTAINMENT; DEPRESSIVE SYMPTOMS; BETWEEN-FAMILY; LIFE-SPAN; PERSONALITY; ABILITIES; INTELLIGENCE AB Intergenerational longitudinal studies over the lifespan provide valuable information for understanding the contexts and dynamic relations among cognition, family and health in adults and the elderly. The Hawai'i Family Study of Cognition (HFSC), initiated in the early 1970s, included a cohort of over 6500 individuals representing over 1800 families of parents and their offspring. The HFSC gathered data on cognitive, personality, biological and other psychosocial variables, and provided novel information on the nature of cognitive abilities, especially on family issues. Some families were reassessed with short-term retesting in the 1970s. A select sample of offspring and their siblings and spouses were re-measured in the 1980s. Decades later, a 40-year follow-up of the original HFSC cohort was facilitated by the availability of contemporary tracking and tracing methods and internet-based testing. A subgroup of the original HFSC participants was re-contacted and retested on contemporary cognitive as well as socio-demographic and health measures. In this paper, we describe the original HFSC cohort and the design and methodology of the re-contact and retest studies of the HFSC, plans for expanding the re-contact and retesting, as well as directions for future research and collaborations. The Principal Investigator may be contacted for more information regarding the application, review and approval process for data access requests from qualified individuals outside the project. C1 [Onoye, Jane M. M.; Hishinuma, Earl S.; Bumanglag, R. Janine; Takeshita, Junji] Univ Hawaii Manoa, Dept Psychiat, Honolulu, HI 96813 USA. [Onoye, Jane M. M.; Takeshita, Junji] Queens Med Ctr, Honolulu, HI USA. [Zonderman, Alan B.] Univ So Calif, Dept Psychol, Los Angeles, CA 90089 USA. [McArdle, John J.] Longitudinal Res Inst, Charlottesville, VA USA. [Zonderman, Alan B.] NIA, Behav Epidemiol Sect, Baltimore, MD 21224 USA. RP Onoye, JMM (reprint author), Univ Hawaii Manoa, Dept Psychiat, 1356 Lusitana St,4th Floor, Honolulu, HI 96813 USA. EM onoyej@dop.hawaii.edu OI Zonderman, Alan B/0000-0002-6523-4778 FU National Institute on Aging at the National Institutes of Health [HHSN311200900372P, HHSN311201000229P, HHSN271201100465P]; University of Southern California [Y71692]; Queen's Medical Center FX The present research and dissemination efforts were supported in part by: the National Institute on Aging at the National Institutes of Health [Contracts HHSN311200900372P; HHSN311201000229P; HHSN271201100465P]; University of Southern California [Contract Y71692]; and the Queen's Medical Center. NR 34 TC 0 Z9 0 U1 1 U2 3 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0300-5771 EI 1464-3685 J9 INT J EPIDEMIOL JI Int. J. Epidemiol. PD DEC PY 2014 VL 43 IS 6 BP 1726 EP 1735 DI 10.1093/ije/dyu012 PG 10 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA CA0AD UT WOS:000348575500015 PM 24639439 ER PT J AU Wright, ME Albanes, D Moser, AB Weinstein, SJ Snyder, K Mannisto, S Gann, PH AF Wright, Margaret E. Albanes, Demetrius Moser, Ann B. Weinstein, Stephanie J. Snyder, Kirk Mannisto, Satu Gann, Peter H. TI Serum phytanic and pristanic acid levels and prostate cancer risk in Finnish smokers SO CANCER MEDICINE LA English DT Article DE Biomarker; diet; phytanic acid; pristanic acid; prostate cancer ID METHYLACYL-COA RACEMASE; PROSPECTIVE COHORT; BETA-CAROTENE; FATTY-ACID; DISEASE; PLASMA; METAANALYSIS; CONSUMPTION; METABOLISM; BIOMARKERS AB Phytanic acid is a saturated branched-chain fatty acid found predominantly in red meat and dairy products, and may contribute to the elevated risks of prostate cancer associated with higher consumption of these foods. Pristanic acid is formed during peroxisomal oxidation of phytanic acid, and is the direct substrate of a-Methyl-CoA-Racemase (AMACR)-an enzyme that is consistently overexpressed in prostate tumors relative to benign tissue. We measured phytanic and pristanic acids as percentages of total fatty acids by gas chromatography-mass spectrometry in prediagnostic blood samples from 300 prostate cancer cases and 300 matched controls, all of whom were participants in the Alpha-Tocopherol, Beta-Carotene Cancer Prevention (ATBC) Study supplementation trial and follow-up cohort. In addition to providing a fasting blood sample at baseline, all men completed extensive diet, lifestyle, and medical history questionnaires. Among controls, the strongest dietary correlates of serum phytanic and pristanic acids were saturated fat, dairy fat, and butter (r = 0.50 and 0.40, 0.46 and 0.38, and 0.40 and 0.37, respectively; all P-values <0.001). There was no association between serum phytanic acid and risk of total or aggressive prostate cancer in multivariate logistic regression models (for increasing quartiles, odds ratios (OR) and 95% confidence intervals (CI) for aggressive cancer were 1.0 (referent), 1.62 (0.97-2.68), 1.12 (0.66-1.90), and 1.14 (0.67-1.94), P-trend = 0.87). Pristanic acid was strongly correlated with phytanic acid levels (r = 0.73, P < 0.0001), and was similarly unrelated to prostate cancer risk. Significant interactions between phytanic and pristanic acids and baseline circulating beta-carotene concentrations were noted in relation to total and aggressive disease among participants who did not receive beta-carotene supplements as part of the original ATBC intervention trial. In summary, we observed no overall association between serum phytanic and pristanic acid levels and prostate cancer risk. Findings indicating that the direction and magnitude of these associations depended upon serum levels of the antioxidant beta-carotene among men not taking beta-carotene supplements should be interpreted cautiously, as they are likely due to chance. C1 [Wright, Margaret E.; Gann, Peter H.] Univ Illinois, Coll Med, Dept Pathol, Chicago, IL 60612 USA. [Wright, Margaret E.] Amer Acad Pediat, Elk Grove Village, IL 60007 USA. [Albanes, Demetrius; Weinstein, Stephanie J.] NCI, Nutr Epidemiol Branch, Div Canc Epidemiol & Genet, NIH,DHHS, Bethesda, MD 20892 USA. [Moser, Ann B.] Kennedy Krieger Inst, Baltimore, MD USA. [Snyder, Kirk] Informat Management Serv Inc, Silver Spring, MD USA. [Mannisto, Satu] Natl Inst Hlth & Welf, Dept Chron Dis Prevent, Helsinki, Finland. RP Wright, ME (reprint author), Amer Acad Pediat, 141 Northwest Point Blvd, Elk Grove Village, IL 60007 USA. EM mwright@aap.org RI Albanes, Demetrius/B-9749-2015; OI Mannisto, Satu/0000-0002-8668-3046 FU American Cancer Society [MSRG-08-109-01-CCE]; Department of Defense [PC050393]; Intramural Research Program of the NIH; National Cancer Institute; U.S. Public Health Service from the National Cancer Institute, Department of Health and Human Services [N01-CN-45165, N01-RC-45035, N01-RC-37004, HHSN261201000006C] FX Supported by American Cancer Society grant MSRG-08-109-01-CCE, Department of Defense grant PC050393, the Intramural Research Program of the NIH and the National Cancer Institute, and U.S. Public Health Service contracts N01-CN-45165, N01-RC-45035, N01-RC-37004 and HHSN261201000006C from the National Cancer Institute, Department of Health and Human Services. NR 34 TC 3 Z9 3 U1 1 U2 11 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 2045-7634 J9 CANCER MED-US JI Cancer Med. PD DEC PY 2014 VL 3 IS 6 BP 1562 EP 1569 DI 10.1002/cam4.319 PG 8 WC Oncology SC Oncology GA AZ4YB UT WOS:000348226000012 PM 25132681 ER PT J AU Owonikoko, TK Zhang, GJ Deng, XM Rossi, MR Switchenko, JM Doho, GH Chen, ZJ Kim, S Strychor, S Christner, SM Beumer, J Li, CY Yue, P Chen, A Sica, GL Ramalingam, SS Kowalski, J Khuri, FR Sun, SY AF Owonikoko, Taofeek K. Zhang, Guojing Deng, Xingming Rossi, Michael R. Switchenko, Jeffrey M. Doho, Gregory H. Chen, Zhengjia Kim, Sungjin Strychor, Sandy Christner, Susan M. Beumer, Jan Li, Chunyang Yue, Ping Chen, Alice Sica, Gabriel L. Ramalingam, Suresh S. Kowalski, Jeanne Khuri, Fadlo R. Sun, Shi-Yong TI Poly (ADP) ribose polymerase enzyme inhibitor, veliparib, potentiates chemotherapy and radiation in vitro and in vivo in small cell lung cancer SO CANCER MEDICINE LA English DT Article DE Carboplatin; cisplatin; etoposide; PARP; SCLC; veliparib (ABT-888) ID DEPENDENT PROTEIN-KINASE; CHROMATIN TRANSCRIPTION FACT; POLY(ADP-RIBOSE) POLYMERASE; DNA-REPAIR; THERAPEUTIC TARGETS; PARP INHIBITORS; OVARIAN-CANCER; BREAST-CANCER; BMN 673; CISPLATIN AB Poly (ADP) ribose polymerase (PARP) plays a key role in DNA repair and is highly expressed in small cell lung cancer (SCLC). We investigated the therapeutic impact of PARP inhibition in SCLC. In vitro cytotoxicity of veliparib, cisplatin, carboplatin, and etoposide singly and combined was determined by MTS in 9 SCLC cell lines (H69, H128, H146, H526, H187, H209, DMS53, DMS153, and DMS114). Subcutaneous xenografts in athymic nu/nu mice of H146 and H128 cells with relatively high and low platinum sensitivity, respectively, were employed for in vivo testing. Mechanisms of differential sensitivity of SCLC cell lines to PARP inhibition were investigated by comparing protein and gene expression profiles of the platinum sensitive and the less sensitive cell lines. Veliparib showed limited single-agent cytotoxicity but selectively potentiated (>= 50% reduction in IC50) cisplatin, carboplatin, and etoposide in vitro in five of nine SCLC cell lines. Veliparib with cisplatin or etoposide or with both cisplatin and etoposide showed greater delay in tumor growth than chemotherapy alone in H146 but not H128 xenografts. The potentiating effect of veliparib was associated with in vitro cell line sensitivity to cisplatin (CC = 0.672; P = 0.048) and DNA-PKcs protein modulation. Gene expression profiling identified differential expression of a 5-gene panel (GLS, UBEC2, HACL1, MSI2, and LOC100129585) in cell lines with relatively greater sensitivity to platinum and veliparib combination. Veliparib potentiates standard cytotoxic agents against SCLC in a cell-specific manner. This potentiation correlates with platinum sensitivity, DNA-PKcs expression and a 5-gene expression profile. C1 [Owonikoko, Taofeek K.; Zhang, Guojing; Yue, Ping; Ramalingam, Suresh S.; Khuri, Fadlo R.; Sun, Shi-Yong] Emory Univ, Sch Med, Dept Hematol & Med Oncol, Atlanta, GA 30322 USA. [Owonikoko, Taofeek K.; Deng, Xingming; Switchenko, Jeffrey M.; Chen, Zhengjia; Kim, Sungjin; Li, Chunyang; Ramalingam, Suresh S.; Kowalski, Jeanne; Khuri, Fadlo R.] Emory Univ, Winship Canc Inst, Atlanta, GA 30322 USA. [Deng, Xingming; Rossi, Michael R.] Emory Univ, Sch Med, Dept Radiat Oncol, Atlanta, GA 30322 USA. [Switchenko, Jeffrey M.; Chen, Zhengjia; Kowalski, Jeanne] Emory Univ, Rollins Sch Publ Hlth, Dept Biostat & Bioinformat, Atlanta, GA 30322 USA. [Doho, Gregory H.] Emory Univ, Sch Med, Emory Integrated Genom Core Lab, Atlanta, GA 30322 USA. [Strychor, Sandy; Christner, Susan M.; Beumer, Jan] Univ Pittsburgh, Mol Therapeut Drug Discovery Program, Inst Canc, Pittsburgh, PA USA. [Chen, Alice] NCI, Invest Drug Branch, Canc Therapy Evaluat Program, Bethesda, MD 20892 USA. [Sica, Gabriel L.] Emory Univ, Sch Med, Dept Pathol, Atlanta, GA 30322 USA. RP Owonikoko, TK (reprint author), Emory Univ, Sch Med, Dept Hematol & Med Oncol, 1365C Clifton Rd NE,Room C3080, Atlanta, GA 30322 USA. EM towonik@emory.edu OI Beumer, Jan/0000-0002-8978-9401 FU NIH [1K23CA164015, P01CA116676, P30CA138292, P30CA47904, U01CA099168]; Georgia Research Alliance Distinguished Cancer Scientist Award FX This work was supported by NIH grants (1K23CA164015, P01CA116676, P30CA138292, P30CA47904, and U01CA099168); and Georgia Research Alliance Distinguished Cancer Scientist Award. NR 52 TC 9 Z9 9 U1 2 U2 13 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 2045-7634 J9 CANCER MED-US JI Cancer Med. PD DEC PY 2014 VL 3 IS 6 BP 1579 EP 1594 DI 10.1002/cam4.317 PG 16 WC Oncology SC Oncology GA AZ4YB UT WOS:000348226000014 PM 25124282 ER PT J AU Richter, S Seah, JA Pond, GR Gan, HK Mackenzie, MJ Hotte, SJ Mukherjee, SD Murray, N Kollmannsberger, C Heng, D Haider, MA Halford, R Ivy, SP Moore, MJ Sridhar, SS AF Richter, Suzanne Seah, Jo-An Pond, Gregory R. Gan, Hui K. Mackenzie, Mary J. Hotte, Sebastien J. Mukherjee, Som D. Murray, Nevin Kollmannsberger, Christian Heng, Daniel Haider, Masoom A. Halford, Robert Ivy, S. Percy Moore, Malcolm J. Sridhar, Srikala S. TI Evaluation of second-line and subsequent targeted therapies in metastatic renal cell cancer (mRCC) patients treated with first-line cediranib SO CUAJ-CANADIAN UROLOGICAL ASSOCIATION JOURNAL LA English DT Article ID PHASE-III TRIAL; INTERFERON-ALPHA; CARCINOMA; SUNITINIB; SORAFENIB; TEMSIROLIMUS AB Introduction: Pivotal phase III trials have positioned angiogenesis inhibitors as first-line therapy for the management of most advanced or metastatic renal cell carcinomas (mRCC). Approaches to secondline therapy, however, remain more controversial with respect to drug selection and drug sequencing. Methods: In this study we evaluated mRCC patients who were initially treated on the first-line National Cancer Institute (NCI) trial with the highly potent vascular endothelial growth factor receptor tyrosine kinase inhibitor (TKI), cediranib, to determine the efficacy and tolerability of subsequent therapies. Results: Twenty-eight (65.1%) of the 43 patients enrolled on the first-line cediranib trial were known to receive second-line therapy, most commonly sunitinib (n = 21), with 4 (14%), 2 (7%) and 1 (3%) patients receiving temsirolimus, sorafenib, and interleukin, respectively. Of these, 14 (50%) went on to have 3 or more lines of therapy. The progression-free survival (PFS) proportion (PFS) at 1 year from starting second line was 30% (14.5%-47.9%). Longer duration of first-line cediranib treatment was modestly associated with longer duration of second-line treatment (Spearman rho 0.26). Patients who discontinued cediranib for toxicity were less likely to receive second-line sunitinib. Conclusion: In this real world evaluation, sequential use of TKIs for the management of mRCC was common. PFS with sequential TKIs was similar to observed and published results for any secondline therapy. Prior toxicity affected treatment patterns and the frequent use of at least 3 lines of therapy underscores the need for prospective sequencing trials in this disease. C1 [Richter, Suzanne; Seah, Jo-An; Halford, Robert; Moore, Malcolm J.; Sridhar, Srikala S.] Princess Margaret Canc Ctr, Toronto, ON, Canada. [Pond, Gregory R.] McMaster Univ, Hamilton, ON, Canada. [Gan, Hui K.] Ludwig Inst Canc Res, Austin Hlth, Melbourne, Vic 3050, Australia. [Mackenzie, Mary J.] Western Univ, London Reg Canc Program, London, ON, Canada. [Hotte, Sebastien J.; Mukherjee, Som D.] McMaster Univ, Juravinski Canc Ctr, Hamilton, ON, Canada. [Murray, Nevin; Kollmannsberger, Christian] Univ British Columbia, BC Canc Agcy, Vancouver, BC V5Z 1M9, Canada. [Heng, Daniel] Univ Alberta, Tom Baker Canc Ctr, Calgary, AB, Canada. [Haider, Masoom A.] Univ Toronto, Sunnybrook Hlth Sci Ctr, Toronto, ON, Canada. [Ivy, S. Percy] NCI, Canc Therapy Evaluat Program, Rockville, MD USA. RP Sridhar, SS (reprint author), Univ Toronto, Princess Margaret Canc Ctr, 5-222,610 Univ Ave, Toronto, ON M5G 6M9, Canada. EM srikala.sridhar@uhn.ca FU NCI NIH HHS [N01CM62203] NR 13 TC 2 Z9 2 U1 0 U2 1 PU CANADIAN UROLOGICAL ASSOCIATION PI DORVAL PA 185 DORVAL AVENUE, STE 401, DORVAL, QC H9S 5J9, CANADA SN 1911-6470 EI 1920-1214 J9 CUAJ-CAN UROL ASSOC JI CUAJ-Can. Urol. Assoc. J. PD DEC PY 2014 VL 8 IS 11-12 BP 398 EP 402 DI 10.5489/cuaj.2426 PG 5 WC Urology & Nephrology SC Urology & Nephrology GA AY6ZJ UT WOS:000347710800024 PM 25553152 ER PT J AU Abate-Daga, D Lagisetty, KH Tran, E Zheng, ZL Gattinoni, L Yu, ZY Burns, WR Miermont, AM Teper, Y Rudloff, U Restifo, NP Feldman, SA Rosenberg, SA Morgan, RA AF Abate-Daga, Daniel Lagisetty, Kiran H. Tran, Eric Zheng, Zhili Gattinoni, Luca Yu, Zhiya Burns, William R. Miermont, Anne M. Teper, Yaroslav Rudloff, Udo Restifo, Nicholas P. Feldman, Steven A. Rosenberg, Steven A. Morgan, Richard A. TI A Novel Chimeric Antigen Receptor Against Prostate Stem Cell Antigen Mediates Tumor Destruction in a Humanized Mouse Model of Pancreatic Cancer SO HUMAN GENE THERAPY LA English DT Article ID ENGINEERED T-CELLS; EXPRESSING TUMORS; CLINICAL-TRIAL; ADVERSE EVENT; PHASE-I; PSCA; THERAPY; MICE; CD28; ADENOCARCINOMA AB Despite advances in the understanding of its molecular pathophysiology, pancreatic cancer remains largely incurable, highlighting the need for novel therapies. We developed a chimeric antigen receptor (CAR) specific for prostate stem cell antigen (PSCA), a glycoprotein that is overexpressed in pancreatic cancer starting at early stages of malignant transformation. To optimize the CAR design, we used antigen-recognition domains derived from mouse or human antibodies, and intracellular signaling domains containing one or two T cell costimulatory elements, in addition to CD3zeta. Comparing multiple constructs established that the CAR based on human monoclonal antibody Ha1-4.117 had the greatest reactivity in vitro. To further analyze this CAR, we developed a human pancreatic cancer xenograft model and adoptively transferred CAR-engineered T cells into animals with established tumors. CAR-engineered human lymphocytes induced significant antitumor activity, and unlike what has been described for other CARs, a second-generation CAR (containing CD28 cosignaling domain) induced a more potent antitumor effect than a third-generation CAR (containing CD28 and 41BB cosignaling domains). While our results provide evidence to support PSCA as a target antigen for CAR-based immunotherapy of pancreatic cancer, the expression of PSCA on selected normal tissues could be a source of limiting toxicity. C1 [Abate-Daga, Daniel; Lagisetty, Kiran H.; Tran, Eric; Zheng, Zhili; Gattinoni, Luca; Yu, Zhiya; Burns, William R.; Miermont, Anne M.; Teper, Yaroslav; Rudloff, Udo; Restifo, Nicholas P.; Feldman, Steven A.; Rosenberg, Steven A.; Morgan, Richard A.] NCI, Surg Branch, NIH, Bethesda, MD 20892 USA. RP Abate-Daga, D (reprint author), NIH, CRC, Bldg 10,Room 3W-3864,10 Ctr Dr, Bethesda, MD 20892 USA. EM daniel.abate-daga@nih.gov RI Gattinoni, Luca/A-2281-2008; OI Gattinoni, Luca/0000-0003-2239-3282; Restifo, Nicholas P./0000-0003-4229-4580 FU Milstein Family Foundation; Intramural Research Program of the Center for Cancer Research, National Cancer Institute, Bethesda, MD FX We would like to thank Arnold Mixon, Shawn Farid, and Dave Jones for technical support. This project was supported in part by a generous contribution from the Milstein Family Foundation and by the Intramural Research Program of the Center for Cancer Research, National Cancer Institute, Bethesda, MD. NR 41 TC 25 Z9 25 U1 0 U2 11 PU MARY ANN LIEBERT, INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1043-0342 EI 1557-7422 J9 HUM GENE THER JI Hum. Gene Ther. PD DEC 1 PY 2014 VL 25 IS 12 BP 1003 EP 1012 DI 10.1089/hum.2013.209 PG 10 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine, Research & Experimental SC Biotechnology & Applied Microbiology; Genetics & Heredity; Research & Experimental Medicine GA AW6AT UT WOS:000346352600077 PM 24694017 ER PT J AU Agochukwu, NB Solomon, BD Muenke, M AF Agochukwu, Nneamaka B. Solomon, Benjamin D. Muenke, Maximilian TI Hearing loss in syndromic craniosynostoses: Otologic manifestations and clinical findings SO INTERNATIONAL JOURNAL OF PEDIATRIC OTORHINOLARYNGOLOGY LA English DT Review DE Craniosynostosis; Syndromic craniosynostosis; Hearing loss craniosynostosis; Hearing loss syndromes; Hearing FGFR syndromes ID BEARE-STEVENSON-SYNDROME; FIBROBLAST-GROWTH-FACTOR; CUTIS-GYRATA-SYNDROME; JACKSON-WEISS-SYNDROME; FACTOR RECEPTOR-2 GENE; PFEIFFER-SYNDROME; CROUZON-SYNDROME; APERT-SYNDROME; ACANTHOSIS NIGRICANS; OTITIS-MEDIA AB Objective: This review addresses hearing loss as it occurs and has been reported in Muenke syndrome as well as six additional FGFR related craniosynostosis syndromes (Apert syndrome, Pfeiffer syndrome, Crouzon syndrome, Beare-Stevenson syndrome, Crouzon syndrome with acanthosis nigricans, and Jackson-Weiss syndrome. Data sources: Pub-Med, Medline, Cochrane Database, Science Direct, NLM Catalog. Review methods: A Medline search was conducted to find all reported cases of the 7 FGFR related syndromic craniosynostosis. Special attention was paid to literature that reported hearing findings and the audiology literature. Results: Hearing loss occurs in variable percentage as a component part of all FGFR related craniosynostosis syndromes. Our literature review revealed the following incidences of hearing loss in FGFR craniosynostoses: 61% in Muenlce syndrome, 80% in Apert Syndrome, 92% in Pfeiffer syndrome, 74% in Crouzon syndrome, 68% in Jackson Weiss syndrome, 4% in Beare Stevenson syndrome and 14% in Crouzon syndrome with Acanthosis Nigricans. The majority of the hearing loss is a conductive hearing loss, with the exception of Muenke syndrome where the majority of patients have a sensorineural hearing loss and Crouzon syndrome where almost half of patients have a pure or component of sensorineural hearing loss. Conclusion: This manuscript presents a diagnostic and management algorithm for patients with syndromic craniosynostosis. It will aid clinicians in treating these patients and further, the recognition of a possible syndrome in patients with hearing loss who also have syndromic features. Published by Elsevier Ireland Ltd. C1 [Agochukwu, Nneamaka B.; Solomon, Benjamin D.; Muenke, Maximilian] NHGRI, Med Genet Branch, NIH, Bethesda, MD 20892 USA. [Agochukwu, Nneamaka B.] NIH, Clin Res Training Program, Bethesda, MD 20892 USA. RP Agochukwu, NB (reprint author), NHGRI, Med Genet Branch, NIH, MSC 3717,Bldg 35,Room 1B-202, Bethesda, MD 20892 USA. EM agochukwunb@mail.nih.gov FU Division of Intramural Research at the National Human Genome Research Institute (National Institutes of Health, Department of Health and Human Services, United States of America) [TTY8664111010] FX We would like to express our gratitude to the patients who participate in our ongoing studies of Muenke syndrome at the NIH. This research was supported by the Division of Intramural Research at the National Human Genome Research Institute (Grant no. TTY8664111010) (National Institutes of Health, Department of Health and Human Services, United States of America). NR 97 TC 3 Z9 3 U1 0 U2 5 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0165-5876 EI 1872-8464 J9 INT J PEDIATR OTORHI JI Int. J. Pediatr. Otorhinolaryngol. PD DEC PY 2014 VL 78 IS 12 BP 2037 EP 2047 DI 10.1016/j.ijporl.2014.09.019 PG 11 WC Otorhinolaryngology; Pediatrics SC Otorhinolaryngology; Pediatrics GA AY6FY UT WOS:000347663800002 PM 25441602 ER PT J AU Davis, BJK Vidal, JS Garcia, M Aspelund, T van Buchem, MA Jonsdottir, MK Sigurdsson, S Harris, TB Gudnason, V Launer, LJ AF Davis, Benjamin J. K. Vidal, Jean-Sebastian Garcia, Melissa Aspelund, Thor van Buchem, Mark A. Jonsdottir, Maria K. Sigurdsson, Sigurdur Harris, Tamara B. Gudnason, Vilmundur Launer, Lenore J. TI The Alcohol Paradox: Light-to-Moderate Alcohol Consumption, Cognitive Function, and Brain Volume SO JOURNALS OF GERONTOLOGY SERIES A-BIOLOGICAL SCIENCES AND MEDICAL SCIENCES LA English DT Article DE Alcohol consumption; Brain aging; Epidemiology; Imaging; Cognitive aging ID OLDER-ADULTS; CARDIOVASCULAR HEALTH; AGES-REYKJAVIK; DEMENTIA; RISK; ASSOCIATION; DECLINE; PERFORMANCE; ROTTERDAM; COHORT AB Background. Studies of older persons show consumption of light-to-moderate amounts of alcohol is positively associated with cognitive function and, separately, is negatively associated with total brain volume (TBV). This is paradoxical as generally, cognitive function is positively associated with TBV. We examined the relationships of TBV, global cognitive function (GCF), and alcohol consumption in a population-based cohort of 3,363 men and women (b. 1907-1935) participating in the Age Gene/Environment Susceptibility-Reykjavik Study (2002-2006) and who were free of dementia or mild cognitive impairment Methods. Drinking status (never, former, and current) and current amount of alcohol consumed were assessed by questionnaire. GCF is a composite score derived from a battery of cognitive tests. TBV, standardized to head size, is estimated quantitatively from brain magnetic resonance imaging. Results. Among women and not men, adjusting for demographic and cardiovascular risk factors, current drinkers had significantly higher GCF scores than abstainers and former drinkers (p < .0001); and GCF was associated with amount consumed. TBV was not associated with drinking status or amount consumed in men or women. GCF and TBV did significantly differ in their associations across alcohol categories (p(interaction) < .001). Within categories of alcohol intake, GCF and TBV were positively associated. Conclusions. The difference in associations of alcohol intake to brain structure and function suggests there may be unmeasured factors that contribute to maintaining better GCF relative to TBV. However, at higher levels of reasonable alcohol consumption, there may be factors leading to reduced brain volume. C1 [Davis, Benjamin J. K.; Vidal, Jean-Sebastian; Garcia, Melissa; Harris, Tamara B.; Launer, Lenore J.] NIA, Lab Epidemiol & Populat Sci, Intramural Res Program, NIH, Bethesda, MD 20892 USA. [Aspelund, Thor; Jonsdottir, Maria K.; Sigurdsson, Sigurdur] Iceland Heart Assoc, Kopavogur, Iceland. [Aspelund, Thor; Gudnason, Vilmundur] Univ Iceland, Ctr Publ Hlth Sci, Reykjavik, Iceland. [van Buchem, Mark A.] Leiden Univ Med Ctr, Dept Radiol, Leiden, Netherlands. [Jonsdottir, Maria K.] Univ Iceland, Fac Psychol, Reykjavik, Iceland. [Jonsdottir, Maria K.] Natl Univ Hosp Iceland, Geriatr Res Ctr Landsptiali, Reykjavik, Iceland. [Gudnason, Vilmundur] Univ Iceland, Fac Med, Reykjavik, Iceland. RP Launer, LJ (reprint author), NIA, Lab Epidemiol & Populat Sci, Intramural Res Program, NIH, 7201 Wisconsin Ave, Bethesda, MD 20892 USA. EM launerl@nia.nih.gov RI Gudnason, Vilmundur/K-6885-2015; Vidal, Jean-Sebastien/D-1941-2016 OI Gudnason, Vilmundur/0000-0001-5696-0084; Vidal, Jean-Sebastien/0000-0001-6770-0720 FU National Institutes of Health [N01-AG-12100]; National Institutes of Health/National Institute on Aging Intramural Research Program; Hjartavernd (the Icelandic Heart Association); Althingi (the Icelandic Parliament); University of Iceland Research Fund FX This work was supported by National Institutes of Health (N01-AG-12100), the National Institutes of Health/National Institute on Aging Intramural Research Program, Hjartavernd (the Icelandic Heart Association), the Althingi (the Icelandic Parliament), and the University of Iceland Research Fund. NR 40 TC 6 Z9 6 U1 2 U2 8 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 1079-5006 EI 1758-535X J9 J GERONTOL A-BIOL JI J. Gerontol. Ser. A-Biol. Sci. Med. Sci. PD DEC PY 2014 VL 69 IS 12 BP 1528 EP 1535 DI 10.1093/gerona/glu092 PG 8 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA AZ6OX UT WOS:000348339800010 PM 24994845 ER PT J AU Su, JM Thompson, P Adesina, A Li, XN Kilburn, L Onar-Thomas, A Kocak, M Chyla, B McKeegan, E Warren, KE Goldman, S Pollack, IF Fouladi, M Chen, A Giranda, V Boyett, J Kun, L Blaney, SM AF Su, Jack M. Thompson, Patrick Adesina, Adekunle Li, Xiao-Nan Kilburn, Lindsay Onar-Thomas, Arzu Kocak, Mehmet Chyla, Brenda McKeegan, Evelyn Warren, Katherine E. Goldman, Stewart Pollack, Ian F. Fouladi, Maryam Chen, Alice Giranda, Vincent Boyett, James Kun, Larry Blaney, Susan M. TI A phase I trial of veliparib (ABT-888) and temozolomide in children with recurrent CNS tumors: a Pediatric Brain Tumor Consortium report SO NEURO-ONCOLOGY LA English DT Article DE ABT-888; CNS tumors; PARP inhibition; pediatric phase I study; veliparib ID POLY(ADP-RIBOSE) POLYMERASE INHIBITOR; ADP-RIBOSE POLYMERASE; HOMOLOGOUS RECOMBINATION REPAIR; REFRACTORY SOLID TUMORS; HIGH-GRADE GLIOMA; PARP INHIBITION; IONIZING-RADIATION; CLINICAL-TRIALS; OVARIAN-CANCER; COMBINATION AB Background. A phase I trial of veliparib (ABT-888), an oral poly(ADP-ribose) polymerase (PARP) inhibitor, and temozolomide (TMZ) was conducted in children with recurrent brain tumors to (i) estimate the maximum tolerated doses (MTDs) or recommended phase II doses (RP2Ds) of veliparib and TMZ; (ii) describe the toxicities of this regimen; and (iii) evaluate the plasma pharmacokinetic parameters and extent of PARP inhibition in peripheral blood mononuclear cells (PBMCs) following veliparib. Methods. TMZ was given once daily and veliparib twice daily for 5 days every 28 days. Veliparib concentrations and poly(ADP-ribose) (PAR) levels in PBMCs were measured on days 1 and 4. Analysis of pharmacokinetic and PBMC PAR levels were performed twice during study conduct to rationally guide dose modifications and to determine biologically optimal MTD/RP2D. Results. Twenty-nine evaluable patients were enrolled. Myelosuppression (grade 4 neutropenia and thrombocytopenia) were dose limiting. The RP2Ds are veliparib 25 mg/m(2) b.i.d. and TMZ 135 mg/m(2)/d. Only 2 out of 12 patients treated at RP2Ds experienced dose-limiting toxicities. Although no objective response was observed, 4 patients had stable disease >6 months in duration, including 1 with glioblastoma multiforme and 1 with ependymoma. At the RP2D of veliparib, pediatric pharmacokinetic parameters were similar to those in adults. Conclusions. Veliparib and TMZ at the RP2D were well tolerated in children with recurrent brain tumors. A phase I/II trial to evaluate the tolerability and efficacy of veliparib, TMZ, and radiation in children with newly diagnosed brainstem gliomas is in progress. C1 [Su, Jack M.; Thompson, Patrick; Adesina, Adekunle; Li, Xiao-Nan; Blaney, Susan M.] Baylor Coll Med, Texas Childrens Canc Ctr, Houston, TX 77030 USA. [Kilburn, Lindsay] Childrens Natl Med Ctr, Washington, DC 20010 USA. [Onar-Thomas, Arzu; Boyett, James; Kun, Larry] St Jude Childrens Res Hosp, Memphis, TN 38105 USA. [Kocak, Mehmet] Univ Tennessee, Hlth Sci Ctr, Knoxville, TN 37996 USA. [Warren, Katherine E.] NCI, Pediat Oncol Branch, Bethesda, MD 20892 USA. [Goldman, Stewart] Childrens Hosp Chicago, Chicago, IL USA. [Pollack, Ian F.] Childrens Hosp Pittsburgh, Pittsburgh, PA USA. [Fouladi, Maryam] Cincinnati Childrens Hosp Med Ctr, Cincinnati, OH 45229 USA. [Chen, Alice] NCI, Canc Therapy Evaluat Program, Bethesda, MD 20892 USA. RP Su, JM (reprint author), 6701 Fannin St,CC1510, Houston, TX 77030 USA. EM jmsu@txch.org FU NIH [U01 CA81457]; American Lebanese Syrian Associated Charities FX This work was supported in part by NIH grant U01 CA81457 for the Pediatric Brain Tumor Consortium and American Lebanese Syrian Associated Charities. NR 37 TC 13 Z9 13 U1 1 U2 7 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 1522-8517 EI 1523-5866 J9 NEURO-ONCOLOGY JI Neuro-Oncology PD DEC PY 2014 VL 16 IS 12 BP 1661 EP 1668 DI 10.1093/neuonc/nou103 PG 8 WC Oncology; Clinical Neurology SC Oncology; Neurosciences & Neurology GA CA0JK UT WOS:000348604000013 PM 24908656 ER PT J AU de Dios, JKL Shrader, JA Joe, GO McClean, JC Williams, K Evers, R Malicdan, MCV Ciccone, C Mankodi, A Huizing, M McKew, JC Bluemke, DA Gahl, WA Carrillo-Carrasco, N AF de Dios, John Karl L. Shrader, Joseph A. Joe, Galen O. McClean, Jeffrey C. Williams, Kayla Evers, Robert Malicdan, May Christine V. Ciccone, Carla Mankodi, Ami Huizing, Marjan McKew, John C. Bluemke, David A. Gahl, William A. Carrillo-Carrasco, Nuria TI Atypical presentation of GNE myopathy with asymmetric hand weakness SO NEUROMUSCULAR DISORDERS LA English DT Article DE GNE myopathy; Inclusion body myopathy 2; Hereditary inclusion body myopathy (HIBM); Nonaka myopathy; Distal myopathy with rimmed vacuoles (DMRV); N-acetylmannosamine (ManNAc); Sialic acid ID INCLUSION-BODY MYOPATHY; DISTAL MYOPATHY; REFERENCE VALUES; RIMMED VACUOLES; ENDOSCOPISTS; SIALYLATION; STRENGTH; GENE AB GNE myopathy is a rare autosomal recessive muscle disease caused by mutations in GNE, the gene encoding the rate-limiting enzyme in sialic acid biosynthesis. GNE myopathy usually manifests in early adulthood with distal myopathy that progresses slowly and symmetrically, first involving distal muscles of the lower extremities, followed by proximal muscles with relative sparing of the quadriceps. Upper extremities are typically affected later in the disease. We report a patient with GNE myopathy who presented with asymmetric hand weakness. He had considerably decreased left grip strength, atrophy of the left anterior forearm and fibro-fatty tissue replacement of left forearm flexor muscles on T1-weighted magnetic resonance imaging. The patient was an endoscopist and thus the asymmetric hand involvement may be associated with left hand overuse in daily repetitive pinching and gripping movements, highlighting the possible impact of environmental factors on the progression of genetic muscle conditions. Published by Elsevier B.V. C1 [de Dios, John Karl L.; Malicdan, May Christine V.; Ciccone, Carla; Huizing, Marjan; Gahl, William A.] NHGRI, MGB, NIH, Bethesda, MD USA. [Shrader, Joseph A.; Joe, Galen O.; Williams, Kayla] NIH, Dept Rehabil Med, Ctr Clin, Bethesda, MD USA. [McClean, Jeffrey C.] San Antonio Mil Med Ctr, Dept Neurol, San Antonio, TX USA. [Evers, Robert; Bluemke, David A.] NIH, Ctr Clin, Bethesda, MD USA. [Mankodi, Ami] NINDS, NIH, Bethesda, MD 20892 USA. [McKew, John C.; Carrillo-Carrasco, Nuria] NIH, NCATS, Bethesda, MD USA. RP Carrillo-Carrasco, N (reprint author), 9000 Rockville Pike,Bldg 31,Room 3B11, Bethesda, MD 20892 USA. EM carrilln@mail.nih.gov RI Carrillo-Carrasco, Nuria/B-9034-2009; OI Carrillo-Carrasco, Nuria/0000-0003-0374-0808; Bluemke, David/0000-0002-8323-8086 FU Intramural NIH HHS [Z99 TR999999] NR 24 TC 3 Z9 3 U1 1 U2 2 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0960-8966 EI 1873-2364 J9 NEUROMUSCULAR DISORD JI Neuromusc. Disord. PD DEC PY 2014 VL 24 IS 12 BP 1063 EP 1067 DI 10.1016/j.nmd.2014.07.006 PG 5 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA AY7XW UT WOS:000347770100005 PM 25182749 ER PT J AU Lee, PT Chao, PK Ou, LC Chuang, JY Lin, YC Chen, SC Chang, HF Law, PY Loh, HH Chao, YS Su, TP Yeh, SH AF Lee, Pin-Tse Chao, Po-Kuan Ou, Li-Chin Chuang, Jian-Ying Lin, Yen-Chang Chen, Shu-Chun Chang, Hsiao-Fu Law, Ping-Yee Loh, Horace H. Chao, Yu-Sheng Su, Tsung-Ping Yeh, Shiu-Hwa TI Morphine drives internal ribosome entry site-mediated hnRNP K translation in neurons through opioid receptor-dependent signaling SO NUCLEIC ACIDS RESEARCH LA English DT Article ID NUCLEAR RIBONUCLEOPROTEIN-K; PERIAQUEDUCTAL GRAY; MESSENGER-RNAS; SPINAL-CORD; PAIN; RAT; PHOSPHORYLATION; TRANSCRIPTION; CONTRIBUTES; ACTIVATION AB Heterogeneous nuclear ribonucleoprotein K (hnRNP K) binds to the promoter region of mu-opioid receptor (MOR) to regulate its transcriptional activity. How hnRNP K contributes to the analgesic effects of morphine, however, is largely unknown. We provide evidence that morphine increases hnRNP K protein expression via MOR activation in rat primary cortical neurons and HEK-293 cells expressing MORs, without increasing mRNA levels. Using the bicistronic reporter assay, we examined whether morphine-mediated accumulation of hnRNP K resulted from translational control. We identified potential internal ribosome entry site elements located in the 5' untranslated regions of hnRNP K transcripts that were regulated by morphine. This finding suggests that internal translation contributes to the morphine-induced accumulation of hnRNP K protein in regions of the central nervous system correlated with nociceptive and antinociceptive modulatory systems in mice. Finally, we found that down-regulation of hnRNP K mediated by siRNA attenuated morphine-induced hyperpolarization of membrane potential in AtT20 cells. Silencing hnRNP K expression in the spinal cord increased nociceptive sensitivity in wild-type mice, but not in MOR-knockout mice. Thus, our findings identify the role of translational control of hnRNP K in morphine-induced analgesia through activation of MOR. C1 [Lee, Pin-Tse; Chao, Po-Kuan; Ou, Li-Chin; Chen, Shu-Chun; Chang, Hsiao-Fu; Chao, Yu-Sheng; Yeh, Shiu-Hwa] Natl Hlth Res Inst, Inst Biotechnol & Pharmaceut Res, Zhunan 35053, Miaoli County, Taiwan. [Chuang, Jian-Ying] Taipei Med Univ, PhD Program Neural Regenerat Med, Taipei 110, Taiwan. [Lin, Yen-Chang] Chinese Culture Univ, Grad Inst Biotechnol, Taipei 11114, Taiwan. [Law, Ping-Yee; Loh, Horace H.] Univ Minnesota, Sch Med, Dept Pharmacol, Minneapolis, MN 55455 USA. [Su, Tsung-Ping] NIDA, Cellular Pathobiol Sect, Intramural Res Program, Baltimore, MD 21224 USA. RP Yeh, SH (reprint author), Natl Hlth Res Inst, Inst Biotechnol & Pharmaceut Res, Zhunan 35053, Miaoli County, Taiwan. EM bau9763@bp.nhri.org.tw RI Yeh, Shiu-Hwa/D-2088-2010; OI Law, Ping-Yee/0000-0002-5364-1093 FU Intramural Research Program of National Health Research Institutes, Taiwan, Republic of China; Ministry of Science and Technology, Taiwan, Republic of China [NSC 101-2325-B-400-005, NSC 102-2325-B-400-005, NSC 103-2325-B-400-018, NSC 101-2311-B-400-005-MY3, NSC 101-2320-B-034-001] FX Intramural Research Program of National Health Research Institutes, Taiwan, Republic of China; and Ministry of Science and Technology, Taiwan, Republic of China [NSC 101-2325-B-400-005, NSC 102-2325-B-400-005, NSC 103-2325-B-400-018, NSC 101-2311-B-400-005-MY3 and NSC 101-2320-B-034-001]. Funding for open access charge: Ministry of Science and Technology, Taiwan, Republic of China [NSC 103-2325-B-400-018]. NR 43 TC 5 Z9 5 U1 0 U2 6 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0305-1048 EI 1362-4962 J9 NUCLEIC ACIDS RES JI Nucleic Acids Res. PD DEC 1 PY 2014 VL 42 IS 21 BP 13012 EP 13025 DI 10.1093/nar/gku1016 PG 14 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA AZ0CS UT WOS:000347914600012 PM 25361975 ER PT J AU Kononenko, AV Bansal, R Lee, NCO Grimes, BR Masumoto, H Earnshaw, WC Larionov, V Kouprina, N AF Kononenko, Artem V. Bansal, Ruchi Lee, Nicholas C. O. Grimes, Brenda R. Masumoto, Hiroshi Earnshaw, William C. Larionov, Vladimir Kouprina, Natalay TI A portable BRCA1-HAC (human artificial chromosome) module for analysis of BRCA1 tumor suppressor function SO NUCLEIC ACIDS RESEARCH LA English DT Article ID TRANSFORMATION-ASSOCIATED RECOMBINATION; CANCER CELL-LINE; CONDITIONAL CENTROMERE; GENE DELIVERY; IONIZING-RADIATION; SATELLITE ARRAYS; BARR BODY; INSTABILITY; DNA; HETEROCHROMATIN AB BRCA1 is involved in many disparate cellular functions, including DNA damage repair, cell-cycle checkpoint activation, gene transcriptional regulation, DNA replication, centrosome function and others. The majority of evidence strongly favors the maintenance of genomic integrity as a principal tumor suppressor activity of BRCA1. At the same time some functional aspects of BRCA1 are not fully understood. Here, a HAC (human artificial chromosome) module with a regulated centromere was constructed for delivery and expression of the 90 kb genomic copy of the BRCA1 gene into BRCA1-deficient human cells. A battery of functional tests was carried out to demonstrate functionality of the exogenous BRCA1. In separate experiments, we investigated the role of BRCA1 in maintenance of heterochromatin integrity within a human functional kinetochore. We demonstrated that BRCA1 deficiency results in a specific activation of transcription of higher-order alphasatellite repeats (HORs) assembled into heterochromatin domains flanking the kinetochore. At the same time no detectable elevation of transcription was observed within HORs assembled into centrochromatin domains. Thus, we demonstrated a link between BRCA1 deficiency and kinetochore dysfunction and extended previous observations that BRCA1 is required to silence transcription in heterochromatin in specific genomic loci. This supports the hypothesis that epigenetic alterations of the kinetochore initiated in the absence of BRCA1 may contribute to cellular transformation. C1 [Kononenko, Artem V.; Lee, Nicholas C. O.; Larionov, Vladimir; Kouprina, Natalay] NCI, Dev Therapeut Branch, Bethesda, MD 20892 USA. [Bansal, Ruchi; Grimes, Brenda R.] Indiana Univ Melvin & Bren Simon Canc Ctr, Indiana Univ Sch Med, Dept Med & Mol Genet, Indianapolis, IN 46202 USA. [Masumoto, Hiroshi] Kazusa DNA, Dept Frontier Res, Lab Cell Engn, Res Inst, Kisarazu, Chiba 2920818, Japan. [Earnshaw, William C.] Univ Edinburgh, Wellcome Trust Ctr Cell Biol, Edinburgh EH9 3JR, Midlothian, Scotland. RP Kouprina, N (reprint author), NCI, Dev Therapeut Branch, Bethesda, MD 20892 USA. EM kouprinn@mail.nih.gov RI Lee, Nicholas/F-3668-2015; OI lee, nicholas/0000-0003-2628-6599 FU Intramural Research Program of the National Institutes of Health (NIH), National Cancer Institute, Center for Cancer Research, USA; Wellcome Trust Principal Research Fellowship [073915]; Ministry of Education, Culture, Sports, Science and Technology of Japan [23247030, 23114008]; Kazusa DNA Research Institute Foundation; Indiana Genomics Initiative (INGEN); Lilly Endowment; NIH FX Intramural Research Program of the National Institutes of Health (NIH), National Cancer Institute, Center for Cancer Research, USA [to V.L. and N.K]; Wellcome Trust Principal Research Fellowship [073915 to W. C.E.]; Grand-in-Aid for Scientific Research from Ministry of Education, Culture, Sports, Science and Technology of Japan [23247030, 23114008 to H.M.]; Kazusa DNA Research Institute Foundation [to H.M.]; Indiana Genomics Initiative (INGEN) [to B. R.G.]. INGEN is supported in part by the Lilly Endowment. Funding for open access charge: NIH. NR 58 TC 4 Z9 4 U1 1 U2 4 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0305-1048 EI 1362-4962 J9 NUCLEIC ACIDS RES JI Nucleic Acids Res. PD DEC 1 PY 2014 VL 42 IS 21 AR e164 DI 10.1093/nar/gku870 PG 15 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA AZ0CS UT WOS:000347914600005 ER PT J AU Grammatikakis, I Panda, AC Abdelmohsen, K Gorospe, M AF Grammatikakis, Ioannis Panda, Amaresh C. Abdelmohsen, Kotb Gorospe, Myriam TI Long noncoding RNAs (lncRNAs) and the molecular hallmarks of aging SO AGING-US LA English DT Article DE long noncoding RNAs; senescence-associated lncRNAs; epigenetic control by lncRNAs; lncRNA regulation of post-transcriptional gene expression; lncRNA influencing aging phenotypes ID PLURIPOTENT STEM-CELLS; HUMAN TUMOR-GROWTH; CELLULAR SENESCENCE; DNA-DAMAGE; HEPATOCELLULAR-CARCINOMA; GENE-EXPRESSION; RIBOSOMAL-RNA; IN-VIVO; TRANSCRIPTIONAL ENHANCERS; HETEROCHROMATIN FORMATION AB During aging, progressive deleterious changes increase the risk of disease and death. Prominent molecular hallmarks of aging are genomic instability, telomere attrition, epigenetic alterations, loss of proteostasis, cellular senescence, stem cell exhaustion, and altered intercellular communication. Long noncoding RNAs (lncRNAs) play important roles in a wide range of biological processes, including age-related diseases like cancer, cardiovascular pathologies, and neurodegenerative disorders. Evidence is emerging that lncRNAs influence the molecular processes that underlie age-associated phenotypes. Here, we review our current understanding of lncRNAs that control the development of aging traits. C1 [Grammatikakis, Ioannis; Panda, Amaresh C.; Abdelmohsen, Kotb; Gorospe, Myriam] NIA, Genet Lab, Intramural Res Program, NIH, Baltimore, MD 21224 USA. RP Abdelmohsen, K (reprint author), NIA, Genet Lab, Intramural Res Program, NIH, Baltimore, MD 21224 USA. EM abdelmohsenk@mail.nih.gov OI PANDA, AMARESH/0000-0003-3189-8995 FU National Institute on Aging-Intramural Research Program of the National Institutes of Health FX This work was supported in its entirety by the National Institute on Aging-Intramural Research Program of the National Institutes of Health. NR 196 TC 22 Z9 23 U1 4 U2 16 PU IMPACT JOURNALS LLC PI ALBANY PA 6211 TIPTON HOUSE, STE 6, ALBANY, NY 12203 USA SN 1945-4589 J9 AGING-US JI Aging-US PD DEC PY 2014 VL 6 IS 12 BP 992 EP 1009 PG 18 WC Cell Biology SC Cell Biology GA AZ2HR UT WOS:000348055500001 PM 25543668 ER PT J AU Rioux-Leclercq, N Ferran, A Mahul, A Argani, P Billis, A Bonsib, S Cheng, L Cheville, J Eble, J Egevad, L Epstein, J Grignon, D Hes, O Humphrey, P Magi-Galluzzi, C Martignoni, G McKenney, J Merino, M Moch, H Montironi, R Netto, G Reuter, V Samaratunga, H Shen, S Srigley, J Tamboli, P Tan, PH Tickoo, S Trpkov, K Zhou, M Delahunt, B Comperat, E AF Rioux-Leclercq, Nathalie Ferran, Algaba Mahul, Amin Argani, Pedram Billis, Athanase Bonsib, Stephen Cheng, Liang Cheville, John Eble, John Egevad, Lars Epstein, Jonathan Grignon, David Hes, Ondrej Humphrey, Peter Magi-Galluzzi, Cristina Martignoni, Guido McKenney, Jesse Merino, Maria Moch, Holger Montironi, Rodolfo Netto, George Reuter, Viktor Samaratunga, Hemamali Shen, Steven Srigley, John Tamboli, Pheroze Tan, Puay Hoon Tickoo, Satish Trpkov, Kiril Zhou, Ming Delahunt, Brett Comperat, Eva TI Renal tumors: The International Society of Urologic Pathology (ISUP) 2012 consensus conference recommendations SO ANNALES DE PATHOLOGIE LA French DT Article DE Renal cancer; ISUP; Recommedations; Consensus conference ID ACQUIRED CYSTIC-DISEASE; COLLECTING DUCT CARCINOMA; CELL-CARCINOMA; CLEAR-CELL; TUBULOCYSTIC CARCINOMA; HEREDITARY LEIOMYOMATOSIS; CLINICOPATHOLOGICAL FEATURES; TRANSLOCATION CARCINOMAS; DIFFERENTIAL-DIAGNOSIS; FOLLICULAR CARCINOMA AB During the last 30 years many advances have been made in kidney tumor pathology. In 1981, 9 entities were recognized in the WHO Classification. In the latest classification of 2004, 50 different types have been recognized. Additional tumor entities have been described since and a wide variety of prognostic parameters have been investigated with variable success; however, much attention has centered upon the importance of features relating to both stage and grade. The International Society of Urological Pathology (ISUP) recommends after consensus conferences the development of reporting guidelines, which have been adopted worldwide ISUP undertook to review all aspects of the pathology of adult renal malignancy through an international consensus conference to be held in 2012. As in the past, participation in this consensus conference was restricted to acknowledged experts in the field. (C) 2014 Elsevier Masson SAS. All rights reserved. C1 [Rioux-Leclercq, Nathalie] CHU Pontchailloux, F-35033 Rennes 9, France. [Ferran, Algaba] Fdn Puigvert Univ Antonomous, Barcelona, Spain. [Mahul, Amin] Cedars Sinai Med Ctr, Los Angeles, CA 90048 USA. [Argani, Pedram] Johns Hopkins Med Inst, Baltimore, MD 21205 USA. [Bonsib, Stephen] Univ Estadual Campinas, Unicamp, Sch Med Sci, Campinas, SP, Brazil. [Cheville, John] Univ Arkansas Med Sci, Little Rock, AR 72212 USA. [Magi-Galluzzi, Cristina] Indiana Univ, Sch Med, Indianapolis, IN 46204 USA. [Cheville, John] Mayo Clin, Rochester, MN USA. [Humphrey, Peter] Karolinska Univ Hosp, Stockholm, Sweden. [Martignoni, Guido] Univ Hosp Plzen, Plzen, Czech Republic. [McKenney, Jesse] Yale Univ, Sch Med, New Haven, CT USA. [Netto, George] Canc Biol & Glickman Urol Inst, Cleveland, OH USA. [Magi-Galluzzi, Cristina] Univ Verona, I-37100 Verona, Italy. [Samaratunga, Hemamali] NCI, Bethesda, MD 20892 USA. [Shen, Steven] Univ Zurich, Zurich, Switzerland. [Cheville, John; Eble, John; Hes, Ondrej] Univ Ancona, Sch Med, Ancona, Italy. [Humphrey, Peter; McKenney, Jesse] Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. [McKenney, Jesse; Moch, Holger] Univ Queensland, Brisbane, Qld, Australia. [Grignon, David; Hes, Ondrej] Cornell Univ, Methodist Hosp, Houston, TX USA. [Srigley, John] Cornell Univ, Weill Med Coll, Houston, TX USA. [Srigley, John] McMaster Univ, Hamilton, ON, Canada. [Tamboli, Pheroze] Univ Otago, Wellington Sch Med & Hlth Sci, Wellington, New Zealand. [Tan, Puay Hoon] Univ Otago, Wellington Sch Med & Hlth Sci, Wellington, New Zealand. [Tickoo, Satish] Univ Calgary, Calgary, AB, Canada. [Trpkov, Kiril] Calgary Lab Serv, Calgary, AB, Canada. [Zhou, Ming] NYU, Med Ctr, New York, NY USA. [Delahunt, Brett] Univ Otago, Wellington Sch Med, Wellington, New Zealand. [Comperat, Eva] UPMC, Hop Pitie Salpetriere, Dept Pathol, F-75651 Paris 13, France. RP Comperat, E (reprint author), UPMC, Hop Pitie Salpetriere, Dept Pathol, 47-83 Blvd Hop, F-75651 Paris 13, France. EM evacomperat@yahoo.fr RI Samaratunga, Hemamali/D-1559-2013; OI Samaratunga, Hemamali/0000-0001-5796-1791; Shen, Steven/0000-0001-7725-1260 NR 63 TC 1 Z9 1 U1 0 U2 2 PU MASSON EDITEUR PI MOULINEAUX CEDEX 9 PA 21 STREET CAMILLE DESMOULINS, ISSY, 92789 MOULINEAUX CEDEX 9, FRANCE SN 0242-6498 J9 ANN PATHOL JI Ann. Pathol. PD DEC PY 2014 VL 34 IS 6 BP 448 EP 461 DI 10.1016/j.annpat.2014.10.003 PG 14 WC Pathology SC Pathology GA AY7IK UT WOS:000347734000004 PM 25499860 ER PT J AU Zipunnikov, V Greven, S Shou, HC Caffo, BS Reich, DS Crainiceanu, CM AF Zipunnikov, Vadim Greven, Sonja Shou, Haochang Caffo, Brian S. Reich, Daniel S. Crainiceanu, Ciprian M. TI LONGITUDINAL HIGH-DIMENSIONAL PRINCIPAL COMPONENTS ANALYSIS WITH APPLICATION TO DIFFUSION TENSOR IMAGING OF MULTIPLE SCLEROSIS SO ANNALS OF APPLIED STATISTICS LA English DT Article DE Principal components; linear mixed model; diffusion tensor imaging; brain imaging data; multiple sclerosis ID FUNCTIONAL MIXED MODELS; REGRESSION; PREDICTORS; FRAMEWORK; PCA AB We develop a flexible framework for modeling high-dimensional imaging data observed longitudinally. The approach decomposes the observed variability of repeatedly measured high-dimensional observations into three additive components: a subject-specific imaging random intercept that quantifies the cross-sectional variability, a subject-specific imaging slope that quantifies the dynamic irreversible deformation over multiple realizations, and a subject-visit-specific imaging deviation that quantifies exchangeable effects between visits. The proposed method is very fast, scalable to studies including ultrahigh-dimensional data, and can easily be adapted to and executed on modest computing infrastructures. The method is applied to the longitudinal analysis of diffusion tensor imaging (DTI) data of the corpus callosum of multiple sclerosis (MS) subjects. The study includes 176 subjects observed at 466 visits. For each subject and visit the study contains a registered DTI scan of the corpus callosum at roughly 30,000 voxels. C1 [Zipunnikov, Vadim; Caffo, Brian S.; Crainiceanu, Ciprian M.] Johns Hopkins Univ, Dept Biostat, Baltimore, MD 21205 USA. [Greven, Sonja] Univ Munich, Dept Stat, D-80539 Munich, Germany. [Shou, Haochang] Univ Penn, Dept Biostat & Epidemiol, Philadelphia, PA 19104 USA. [Reich, Daniel S.] NINDS, NIH, Bethesda, MD 20824 USA. RP Zipunnikov, V (reprint author), Johns Hopkins Univ, Dept Biostat, Baltimore, MD 21205 USA. EM vzipunn1@jhu.edu RI Reich, Daniel/E-5701-2010 OI Reich, Daniel/0000-0002-2628-4334 FU National Institute of Neurological Disorders and Stroke [R01NS060910]; NIH National Institute of Biomedical Imaging and Bioengineering (NIBIB) [EB012547]; German Research Foundation through the Emmy Noether Programme, Grant [GR 3793/1-1]; Intramural Research Program of the National Institute of Neurological Disorders and Stroke FX Supported by Grant R01NS060910 from the National Institute of Neurological Disorders and Stroke and by Award Number EB012547 from the NIH National Institute of Biomedical Imaging and Bioengineering (NIBIB).; Supported by the German Research Foundation through the Emmy Noether Programme, Grant GR 3793/1-1.; Supported by the Intramural Research Program of the National Institute of Neurological Disorders and Stroke. NR 44 TC 4 Z9 4 U1 1 U2 7 PU INST MATHEMATICAL STATISTICS PI CLEVELAND PA 3163 SOMERSET DR, CLEVELAND, OH 44122 USA SN 1932-6157 J9 ANN APPL STAT JI Ann. Appl. Stat. PD DEC PY 2014 VL 8 IS 4 BP 2175 EP 2202 DI 10.1214/14-AOAS748 PG 28 WC Statistics & Probability SC Mathematics GA AY4EF UT WOS:000347530200014 PM 25663955 ER PT J AU Zhang, ZW Nie, L Soon, GX Liu, AY AF Zhang, Zhiwei Nie, Lei Soon, Guoxing Liu, Aiyi TI THE USE OF COVARIATES AND RANDOM EFFECTS IN EVALUATING PREDICTIVE BIOMARKERS UNDER A POTENTIAL OUTCOME FRAMEWORK SO ANNALS OF APPLIED STATISTICS LA English DT Article DE Conditional independence; counterfactual; ROC regression; sensitivity analysis; treatment effect heterogeneity; treatment selection ID TREATMENT-SELECTION; TRIAL; CANCER AB Predictive or treatment selection biomarkers are usually evaluated in a subgroup or regression analysis with focus on the treatment-by-marker interaction. Under a potential outcome framework (Huang, Gilbert and Janes [Biometrics 68 (2012) 687-696]), a predictive biomarker is considered a predictor for a desirable treatment benefit (defined by comparing potential outcomes for different treatments) and evaluated using familiar concepts in prediction and classification. However, the desired treatment benefit is unobservable because each patient can receive only one treatment in a typical study. Huang et al. overcome this problem by assuming monotonicity of potential outcomes, with one treatment dominating the other in all patients. Motivated by an HIV example that appears to violate the monotonicity assumption, we propose a different approach based on covariates and random effects for evaluating predictive biomarkers under the potential outcome framework. Under the proposed approach, the parameters of interest can be identified by assuming conditional independence of potential outcomes given observed covariates, and a sensitivity analysis can be performed by incorporating an unobserved random effect that accounts for any residual dependence. Application of this approach to the motivating example shows that baseline viral load and CD4 cell count are both useful as predictive biomarkers for choosing antiretroviral drugs for treatment-naive patients. C1 [Zhang, Zhiwei] US FDA, Div Biostat, Off Surveillance & Biometr, Ctr Devices & Radiol Hlth, Silver Spring, MD 20993 USA. [Nie, Lei] US FDA, Div Biometr 5, Off Biostat, Ctr Drug Evaluat & Res, Silver Spring, MD 20993 USA. [Soon, Guoxing] US FDA, Div Biometr 4, Off Biostat, Ctr Drug Evaluat & Res, Silver Spring, MD 20993 USA. [Liu, Aiyi] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Biostat & Bioinformat Branch, Div Intramural Population Hlth Res, NIH, Bethesda, MD 20892 USA. RP Zhang, ZW (reprint author), US FDA, Div Biostat, Off Surveillance & Biometr, Ctr Devices & Radiol Hlth, 10903 New Hampshire Ave, Silver Spring, MD 20993 USA. EM zhiwei.zhang@fda.hhs.gov; lei.nie@fda.hhs.gov; guoxing.soon@fda.hhs.gov; liua@mail.nih.gov OI Liu, Aiyi/0000-0002-6618-5082 FU Intramural NIH HHS [ZIA HD008875-01] NR 25 TC 1 Z9 1 U1 1 U2 6 PU INST MATHEMATICAL STATISTICS PI CLEVELAND PA 3163 SOMERSET DR, CLEVELAND, OH 44122 USA SN 1932-6157 J9 ANN APPL STAT JI Ann. Appl. Stat. PD DEC PY 2014 VL 8 IS 4 BP 2336 EP 2355 DI 10.1214/14-AOAS773 PG 20 WC Statistics & Probability SC Mathematics GA AY4EF UT WOS:000347530200021 PM 26779295 ER PT J AU Bornstein, MH Esposito, G AF Bornstein, Marc H. Esposito, Gianluca TI Beyond cry and laugh: Toward a multilevel model of language production SO BEHAVIORAL AND BRAIN SCIENCES LA English DT Editorial Material ID DISORDER; INFANTS AB Language production is a multilevel phenomenon, and human capacities to communicate vocally progress from early forms, based on projections of motor cortex to brainstem nuclei, to complex elaborations, mediated by high-order cognition and fostered by socially mediated feedback. C1 [Bornstein, Marc H.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Bethesda, MD 20892 USA. [Esposito, Gianluca] Univ Trento, Dept Psychol & Cognit Sci, I-38068 Trento, Italy. [Esposito, Gianluca] Nanyang Technol Univ, Div Psychol, Singapore 639798, Singapore. RP Bornstein, MH (reprint author), Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Rockledge 1, Bethesda, MD 20892 USA. EM Marc_H_Bornstein@nih.gov; gianluca.esposito@unitn.it NR 9 TC 0 Z9 0 U1 0 U2 4 PU CAMBRIDGE UNIV PRESS PI NEW YORK PA 32 AVENUE OF THE AMERICAS, NEW YORK, NY 10013-2473 USA SN 0140-525X EI 1469-1825 J9 BEHAV BRAIN SCI JI Behav. Brain Sci. PD DEC PY 2014 VL 37 IS 6 DI 10.1017/S0140525X13003968 PG 4 WC Psychology, Biological; Behavioral Sciences; Neurosciences SC Psychology; Behavioral Sciences; Neurosciences & Neurology GA AZ2IE UT WOS:000348056700004 ER PT J AU Maity, J Bohr, VA Laskar, A Karmakar, P AF Maity, Jyotirindra Bohr, Vilhelm A. Laskar, Aparna Karmakar, Parimal TI Transient overexpression of Werner protein rescues starvation induced autophagy in Werner syndrome cells SO BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR BASIS OF DISEASE LA English DT Article DE Autophagy; Aging; Beclin-1; RecQ helicase; Werner protein; Werner syndrome ID RNA-POLYMERASE-I; RECQ HELICASES; MAMMALIAN TARGET; DNA-DAMAGE; TRANSCRIPTION; WRN; EXPRESSION; DISEASE; CANCER; REPAIR AB Reduced autophagy may be associated with normal and pathological aging. Here we report a link between autophagy and Werner protein (WRNp), mutated in Werner syndrome, the human premature aging Werner syndrome (WS). WRN mutant fibroblast AG11395 and AG05229 respond weakly to starvation induced autophagy compared to normal cells. While the fusion of phagosomes with lysosome is normal, WS cells contain fewer autophagy vacuoles. Cellular starvation autophagy in WS cells is restored after transfection with full length WRN. Further, siRNA mediated silencing of WRN in the normal fibroblast cell line WI-38 results in decreased autophagy and altered expression of autophagy related proteins. Thus, our observations suggest that WRN may have a role in controlling autophagy and hereby cellular maintenance. (C) 2014 Elsevier B.V. All rights reserved. C1 [Maity, Jyotirindra; Karmakar, Parimal] Jadavpur Univ, Dept Life Sci & Biotechnol, Kolkata 700032, India. [Bohr, Vilhelm A.] NIA, Lab Mol Gerontol, NIH, Baltimore, MD 21224 USA. [Laskar, Aparna] CSIR, Indian Inst Chem Biol, Kolkata 700032, India. RP Karmakar, P (reprint author), Jadavpur Univ, Dept Life Sci & Biotechnol, Kolkata 700032, W Bengal, India. EM pkarmakar_28@yahoo.co.in FU Council for Scientific and Industrial Research (CSIR), Government of India [37/(1442)/10/EMR-II]; National Institute on Aging, NIH FX The authors would like to acknowledge for financial support for this research work the Council for Scientific and Industrial Research (CSIR), project no: [37/(1442)/10/EMR-II] Government of India. We sincerely acknowledge Dr. Jayanta Debnath (Department of Pathology, University California, San Francisco) for pBABE-puro mCherry-EGFP-LC3B and Prof. Tamatsu Yoshimori (Osaka, Japan) for EGFP-LC3 plasmid. We also express sincere thanks to Prof. S. Roy, Director, Indian Institute of Chemical Biology, Kolkata, India, for his permission to use the transmission electron microscope. This project was partially supported by funds from the Intramural program of the National Institute on Aging, NIH. NR 45 TC 2 Z9 2 U1 1 U2 6 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0925-4439 EI 0006-3002 J9 BBA-MOL BASIS DIS JI Biochim. Biophys. Acta-Mol. Basis Dis. PD DEC PY 2014 VL 1842 IS 12 BP 2387 EP 2394 DI 10.1016/j.bbadis.2014.09.007 PN A PG 8 WC Biochemistry & Molecular Biology; Biophysics; Cell Biology SC Biochemistry & Molecular Biology; Biophysics; Cell Biology GA AY5CK UT WOS:000347590700005 PM 25257404 ER PT J AU Castoria, G Giovannelli, P Di Donato, M Ciociola, A Hayashi, R Bernal, F Appella, E Auricchio, F Migliaccio, A AF Castoria, G. Giovannelli, P. Di Donato, M. Ciociola, A. Hayashi, R. Bernal, F. Appella, E. Auricchio, F. Migliaccio, A. TI Role of non-genomic androgen signalling in suppressing proliferation of fibroblasts and fibrosarcoma cells SO CELL DEATH & DISEASE LA English DT Article ID GROWTH-FACTOR RECEPTOR; DEPENDENT NUCLEAR EXPORT; BREAST-CANCER CELLS; PROSTATE-CANCER; ESTRADIOL-RECEPTOR; CYCLE PROGRESSION; RAS ONCOGENES; DNA-SYNTHESIS; STAPLED P53; IN-VIVO AB The functions of androgen receptor (AR) in stromal cells are still debated in spite of the demonstrated importance of these cells in organ development and diseases. Here, we show that physiological androgen concentration (10 nM R1881 or DHT) fails to induce DNA synthesis, while it consistently stimulates cell migration in mesenchymal and transformed mesenchymal cells. Ten nanomolar R1881 triggers p27 Ser10 phosphorylation and its stabilization in NIH3T3 fibroblasts. Activation of Rac and its downstream effector DYRK 1B is responsible for p27 Ser10 phosphorylation and cell quiescence. Ten nanomolar androgen also inhibits transformation induced by oncogenic Ras in NIH3T3 fibroblasts. Overexpression of an AR mutant unable to interact with filamin A, use of a small peptide displacing AR/filamin A interaction, and filamin A knockdown indicate that the androgen-triggered AR/filamin A complex regulates the pathway leading to p27 Ser10 phosphorylation and cell cycle arrest. As the AR/filamin A complex is also responsible for migration stimulated by 10 nM androgen, our report shows that the androgen-triggered AR/filamin A complex controls, through Rac 1, the decision of cells to halt cell cycle and migration. This study reveals a new and unexpected role of androgen/AR signalling in coordinating stromal cell functions. C1 [Castoria, G.; Giovannelli, P.; Di Donato, M.; Ciociola, A.; Auricchio, F.; Migliaccio, A.] Univ Naples Federico II, Dept Biochem Biophys & Gen Pathol, I-80138 Naples, Italy. [Hayashi, R.; Appella, E.] NCI, Lab Cell Biol, Bethesda, MD 20892 USA. [Bernal, F.] NCI, Metabol Branch, Bethesda, MD 20892 USA. RP Castoria, G (reprint author), Univ Naples Federico II, Dept Biochem Biophys & Gen Pathol, Via L De Crecchio 7, I-80138 Naples, Italy. EM gabriella.castoria@unina2.it; antimo.migliaccio@unina2.it OI Migliaccio, Antimo/0000-0002-4197-2055; Di Donato, Marzia/0000-0001-7207-826X; Castoria, Gabriella/0000-0002-0576-4494 FU Italian Association for Cancer Research [IG11520]; Italian Ministry of University and Scientific Research (P.R.I.N.) [2010NFEB9L_002]; Italian Ministry of University and Scientific Research FX We thank M.V. Barone for Src- and Ras-transformed fibroblasts, F. Claessens for 3416 and 3424 constructs, P. Coffer for pGL2-p27 construct, E.L. Yong for Delta 622-670 hAR mutant, P. Friedl for human fibrosarcoma HT1080 cells, and M. Pagano for HA-tagged wt p27 and S10A constructs. The Italian Association for Cancer Research (IG11520 to A. M.) and the Italian Ministry of University and Scientific Research (P.R.I.N. 2010-2011; 2010NFEB9L_002 to G.C.) supported this work. Pia Giovannelli and Marzia Di Donato are supported by a fellowship of the Italian Ministry of University and Scientific Research. NR 52 TC 7 Z9 7 U1 0 U2 5 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 2041-4889 J9 CELL DEATH DIS JI Cell Death Dis. PD DEC PY 2014 VL 5 AR e1548 DI 10.1038/cddis.2014.497 PG 12 WC Cell Biology SC Cell Biology GA AY8YU UT WOS:000347837400001 PM 25476896 ER PT J AU Li, Y Hong, N Zhang, A Chen, W Wang, RH Xu, XL Deng, CX AF Li, Y. Hong, N. Zhang, A. Chen, W. Wang, R-H Xu, X-L Deng, C-X TI Enhancing mammary differentiation by overcoming lineage-specific epigenetic modification and signature gene expression of fibroblast-derived iPSCs SO CELL DEATH & DISEASE LA English DT Article ID PLURIPOTENT STEM-CELLS; CLAUDIN-7 EXPRESSION; DNA-METHYLATION; MOUSE; GLAND; HETEROGENEITY; MORPHOGENESIS; CARCINOMA; MEDICINE; BRCA1 AB Recent studies have shown that induced pluripotent stem cells (iPSCs) retain a memory of their origin and exhibit biased differentiation potential. This finding reveals a severe limitation in the application of iPSCs to cell-based therapy because it means that certain cell types are not available for reprogramming for patients. Here we show that the iPSC differentiation process is accompanied by profound gene expression and epigenetic modifications that reflect cells' origins. Under typical conditions for mammary differentiation, iPSCs reprogrammed from tail-tip fibroblasts (TF-iPSCs) activated a fibroblast-specific signature that was not compatible with mammary differentiation. Strikingly, under optimized conditions, including coculture with iPSCs derived from the mammary epithelium or in the presence of pregnancy hormones, the fibroblast-specific signature of TF-iPSCs obtained during differentiation was erased and cells displayed a mammary-specific signature with a markedly enhanced ability for mammary differentiation. These findings provide new insights into the precise control of differentiation conditions that may have applications in personalized cell-based therapy. C1 [Li, Y.; Hong, N.; Zhang, A.; Wang, R-H; Xu, X-L; Deng, C-X] NIDDK, Genet Dev & Dis Branch, NIH, Bethesda, MD 20892 USA. [Li, Y.] Third Mil Med Univ, Xin Qiao Hosp, Chongqing, Peoples R China. [Chen, W.] NIDDK, Microarray Core Facil, NIH, Bethesda, MD 20892 USA. [Wang, R-H; Xu, X-L; Deng, C-X] Univ Macau, Fac Hlth Sci, Macau, Macau Sar, Peoples R China. RP Deng, CX (reprint author), NIDDK, Genet Dev & Dis Branch, NIH, 10-9N105, Bethesda, MD 20892 USA. EM chuxiad@bdg10.niddk.nih.gov FU Intramural Research Program of the National Institute of Diabetes, Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD, USA FX We thank Dr Gertraud Robinson for technical assistance in mammary fat pat implantation and members of the Deng laboratory for the critical reading of and helpful discussion about this manuscript. This work was supported by the Intramural Research Program of the National Institute of Diabetes, Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD, USA. NR 41 TC 1 Z9 1 U1 0 U2 8 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 2041-4889 J9 CELL DEATH DIS JI Cell Death Dis. PD DEC PY 2014 VL 5 AR e1550 DI 10.1038/cddis.2014.499 PG 12 WC Cell Biology SC Cell Biology GA AY8YU UT WOS:000347837400003 PM 25476898 ER PT J AU Freedman, BR Brindle, TJ Sheehan, FT AF Freedman, Benjamin R. Brindle, Timothy J. Sheehan, Frances T. TI Re-evaluating the functional implications of the Q-angle and its relationship to in-vivo patellofemoral kinematics SO CLINICAL BIOMECHANICS LA English DT Article DE Patellofemoral joint; Patellofemoral pain syndrome; Magnetic resonance imaging; Kinematics; Knee ID ANTERIOR KNEE PAIN; PHYSICAL-EXAMINATION; GENDER-DIFFERENCES; PATELLAR TRACKING; BIOMECHANICS; POSITION; WOMEN; JOINT; MEN; DISORDERS AB Background: The Q-angle is widely used clinically to evaluate individuals with anterior knee pain. Recent studies have questioned the utility of this measure and have suggested that a large Q-angle may not be associated with lateral patellofemoral translation, as often assumed. The objective of this study was to determine: 1) how accurately the Q-angle represents the line-of-action of the quadriceps and 2) if adding active quadriceps contraction or a bent knee position to the measurement of the Q-angle improves its reliability, accuracy, and association with patellofemoral kinematics. Methods: The study included individuals diagnosed with chronic idiopathic patellofemoral pain and control subjects (n = 43 and n = 30 knees). Three measures of the clinical Q-angle (straight- and bent-knee with relaxed quadriceps and straight-knee with maximum isometric quadriceps contraction) were obtained with a goniometer and compared to a fourth MR-based measure of Q-angle. Patellofemoral kinematics were derived from dynamic cine-phase contrast images, acquired while subjects extended/flexed their knee from approximately 0 degrees and 45 degrees. Findings: The Q-angle did not represent the line-of-action of the quadriceps. The average difference between each clinical and the MR-based Q-angle ranged from 5 degrees to 8 degrees. These differences varied greatly across subjects (range: -28.5 degrees to 3.9 degrees). Adding an active quadriceps contraction or a bent knee position, did not improve the reliability of the Q-angle. An increased Q-angle correlated to medial patellar displacement and tilt (r = 0.38-0.54, P < 0.001) in the cohort with anterior knee pain. Interpretation: Clinicians are cautioned against using the Q-angle to infer patellofemoral kinematics. (C) 2014 Published by Elsevier Ltd. C1 [Freedman, Benjamin R.; Sheehan, Frances T.] NIH, Dept Rehabil Med, Bethesda, MD 20892 USA. [Brindle, Timothy J.] Univ Maryland, College Pk, MD 20742 USA. [Freedman, Benjamin R.] Univ Penn, Dept Bioengn, Philadelphia, PA 19104 USA. RP Freedman, BR (reprint author), Univ Penn, McKay Orthopaed Res Lab, 424 Stemmler Hal,36th & Hamilton Walk, Philadelphia, PA 19104 USA. EM bfreed@seas.upenn.edu FU NIH Clinical Center Intramural Research Program; Biomedical Engineering Summer Internship Program - National Institute of Biomedical Imaging and Bioengineering; Diagnostic Radiology Department at the National Institutes of Health FX This research was supported by the NIH Clinical Center Intramural Research Program and the Biomedical Engineering Summer Internship Program (funded by the National Institute of Biomedical Imaging and Bioengineering). Special thanks are given to Sara Sadeghi, Abrahm Behnam, Cris Zampieri-Gallagher, Ching Yi Shieh, Bonnie Damaska, and the Diagnostic Radiology Department at the National Institutes of Health for their support and research time. NR 42 TC 4 Z9 6 U1 1 U2 11 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0268-0033 EI 1879-1271 J9 CLIN BIOMECH JI Clin. Biomech. PD DEC PY 2014 VL 29 IS 10 BP 1139 EP 1145 DI 10.1016/j.clinbiomech.2014.09.012 PG 7 WC Engineering, Biomedical; Orthopedics; Sport Sciences SC Engineering; Orthopedics; Sport Sciences GA AY5CW UT WOS:000347591800009 PM 25451861 ER PT J AU Gao, X Cao, HB Ming, D Qi, HZ Wang, XM Wang, XL Chen, RG Zhou, P AF Gao, Xiang Cao, Hongbao Ming, Dong Qi, Hongzhi Wang, Xuemin Wang, Xiaolu Chen, Runge Zhou, Peng TI Analysis of EEG activity in response to binaural beats with different frequencies SO INTERNATIONAL JOURNAL OF PSYCHOPHYSIOLOGY LA English DT Article DE Binaural beat; Connectivity; RP; PLV; CMI ID ATTENTION-DEFICIT/HYPERACTIVITY DISORDER; MUTUAL INFORMATION ANALYSIS; FUNCTIONAL-ORGANIZATION; HYPNOTIC-SUSCEPTIBILITY; SCHIZOPHRENIC-PATIENTS; AUDITORY BEATS; PHASE-LOCKING; BRAIN; COHERENCE; NEUROFEEDBACK AB When two coherent sounds with nearly similar frequencies are presented to each ear respectively with stereo headphones, the brain integrates the two signals and produces a sensation of a third sound called binaural beat (BB). Although earlier studies showed that BB could influence behavior and cognition, common agreement on the mechanism of BB has not been reached yet. In this work, we employed Relative Power (RP), Phase Locking Value (PLV) and Cross-Mutual Information (CMI) to track EEG changes during BB stimulations. EEG signals were acquired from 13 healthy subjects. Five-minute BBs with four different frequencies were tested: delta band (1 Hz), theta band (5 Hz), alpha band (10 Hz) and beta band (20 Hz). We observed RP increase in theta and alpha bands and decrease in beta band during delta and alpha BB stimulations. RP decreased in beta band during theta BB, while RP decreased in theta band during beta BB. However, no clear brainwave entrainment effect was identified. Connectivity changes were detected following the variation of RP during BB stimulations. Our observation supports the hypothesis that BBs could affect functional brain connectivity, suggesting that the mechanism of BB-brain interaction is worth further study. (C) 2014 Published by Elsevier B.V. C1 [Gao, Xiang; Ming, Dong; Qi, Hongzhi; Wang, Xuemin; Wang, Xiaolu; Chen, Runge; Zhou, Peng] Tianjin Univ, Sch Precis Instruments & Optoelect Engn, Tianjin 300072, Peoples R China. [Cao, Hongbao] NIMH, Unit Stat Genom, NIH, Bethesda, MD 20852 USA. RP Zhou, P (reprint author), Tianjin Univ, Sch Precis Instruments & Optoelect Engn, Tianjin 300072, Peoples R China. EM zpzpa@vip.sina.com FU National Natural Science Foundation of China [51377120, 81222021, 31271062, 61172008, 81171423, 51007063]; National Key Technology R&D Program of the Ministry of Science and Technology of China [2012BAI34B02]; Program for New Century Excellent Talents in University of the Ministry of Education of China [NCET-10-0618] FX This research was supported by the National Natural Science Foundation of China (No. 51377120, 81222021, 31271062, 61172008, 81171423, 51007063), the National Key Technology R&D Program of the Ministry of Science and Technology of China (No. 2012BAI34B02) and the Program for New Century Excellent Talents in University of the Ministry of Education of China (No. NCET-10-0618). NR 50 TC 10 Z9 11 U1 10 U2 40 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0167-8760 EI 1872-7697 J9 INT J PSYCHOPHYSIOL JI Int. J. Psychophysiol. PD DEC PY 2014 VL 94 IS 3 BP 399 EP 406 DI 10.1016/j.ijpsycho.2014.10.010 PG 8 WC Psychology, Biological; Neurosciences; Physiology; Psychology; Psychology, Experimental SC Psychology; Neurosciences & Neurology; Physiology GA AZ1RI UT WOS:000348015200017 PM 25448376 ER PT J AU Karev, GP AF Karev, Georgy P. TI Non-linearity and heterogeneity in modeling of population dynamics SO MATHEMATICAL BIOSCIENCES LA English DT Article DE Non-exponential growth; Distributed parameters; Heterogeneous population; Prebiological evolution ID REPLICATORS; GROWTH; REPRODUCERS; TEMPLATES; SURVIVAL AB The study of population growth reveals that the behaviors that follow the power law appear in numerous biological, demographical, ecological, physical and other contexts. Parabolic models appear to be realistic approximations of real-life replicator systems, while hyperbolic models were successfully applied to problems of global demography and appear relevant in quasispecies and hypercycle modeling. Nevertheless, it is not always clear why non-exponential growth is observed empirically and what possible origins of the non-exponential models are. In this paper the power equation is considered within the frameworks of inhomogeneous population models; it is proven that any power equation describes the total population size of a frequency-dependent model with Gamma-distributed Malthusian parameter. Additionally, any super-exponential equation describes the dynamics of inhomogeneous Malthusian density-dependent population model. All statistical characteristics of the underlying inhomogeneous models are computed explicitly. The results of this analysis show that population heterogeneity can be a reasonable explanation for power law accurately describing total population growth. (C) 2014 Elsevier Inc. All rights reserved. C1 NIH, Natl Ctr Biotechnol Informat, Bethesda, MD 20894 USA. RP Karev, GP (reprint author), NIH, Natl Ctr Biotechnol Informat, Bldg 38A,8600 Rockville Pike, Bethesda, MD 20894 USA. EM karev@ncbi.nlm.nih.gov FU NIH, NCBI FX This research was supported by the Intramural Research Program of the NIH, NCBI. NR 34 TC 2 Z9 2 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0025-5564 EI 1879-3134 J9 MATH BIOSCI JI Math. Biosci. PD DEC PY 2014 VL 258 BP 85 EP 92 DI 10.1016/j.mbs.2014.09.010 PG 8 WC Biology; Mathematical & Computational Biology SC Life Sciences & Biomedicine - Other Topics; Mathematical & Computational Biology GA AZ1TN UT WOS:000348020700009 PM 25262656 ER PT J AU Morissette, R McDonnell, NB Merke, DP AF Morissette, Rachel McDonnell, Nazli B. Merke, Deborah P. TI Tenascin-X gene defects and cardiovascular disease SO MEDICAL HYPOTHESES LA English DT Letter ID EHLERS-DANLOS-SYNDROME C1 [Morissette, Rachel] NIH, Ctr Clin, Bethesda, MD 20892 USA. [McDonnell, Nazli B.] NIA, NIH, Baltimore, MD 21224 USA. [Merke, Deborah P.] NIH, Ctr Clin, CRC, Bethesda, MD 20892 USA. [Merke, Deborah P.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Bethesda, MD USA. RP Morissette, R (reprint author), NIH, Ctr Clin, Bethesda, MD 20892 USA. EM dmerke@nih.gov FU Intramural NIH HHS NR 3 TC 0 Z9 0 U1 1 U2 3 PU CHURCHILL LIVINGSTONE PI EDINBURGH PA JOURNAL PRODUCTION DEPT, ROBERT STEVENSON HOUSE, 1-3 BAXTERS PLACE, LEITH WALK, EDINBURGH EH1 3AF, MIDLOTHIAN, SCOTLAND SN 0306-9877 EI 1532-2777 J9 MED HYPOTHESES JI Med. Hypotheses PD DEC PY 2014 VL 83 IS 6 BP 844 EP 844 DI 10.1016/j.mehy.2014.01.027 PG 1 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA AY5EJ UT WOS:000347595600046 PM 24709065 ER PT J AU Li, QT Zou, J Wang, MJ Ding, XL Chepelev, I Zhou, XK Zhao, W Wei, G Cui, J Zhao, KJ Wang, HY Wang, RF AF Li, Qingtian Zou, Jia Wang, Mingjun Ding, Xilai Chepelev, Iouri Zhou, Xikun Zhao, Wei Wei, Gang Cui, Jun Zhao, Keji Wang, Helen Y. Wang, Rong-Fu TI Critical role of histone demethylase Jmjd3 in the regulation of CD4(+) T-cell differentiation SO NATURE COMMUNICATIONS LA English DT Article ID EMBRYONIC STEM-CELLS; EPIGENETIC CONTROL; GENE-EXPRESSION; MOLECULAR-MECHANISMS; TRANSCRIPTION FACTOR; MEDIATED REPRESSION; LINEAGE COMMITMENT; HELPER TYPE-1; IMMUNE-SYSTEM; T(H)17 CELLS AB Epigenetic factors have been implicated in the regulation of CD4(+) T-cell differentiation. Jmjd3 plays a role in many biological processes, but its in vivo function in T-cell differentiation remains unknown. Here we report that Jmjd3 ablation promotes CD4(+) T-cell differentiation into Th2 and Th17 cells in the small intestine and colon, and inhibits T-cell differentiation into Th1 cells under different cytokine-polarizing conditions and in a Th1-dependent colitis model. Jmjd3 deficiency also restrains the plasticity of the conversion of Th2, Th17 or Treg cells to Th1 cells. The skewing of T-cell differentiation is concomitant with changes in the expression of key transcription factors and cytokines. H3K27me3 and H3K4me3 levels in Jmjd3-deficient cells are correlated with altered gene expression through interactions with specific transcription factors. Our results identify Jmjd3 as an epigenetic factor in T-cell differentiation via changes in histone methylation and target gene expression. C1 [Li, Qingtian; Zou, Jia; Wang, Mingjun; Ding, Xilai; Zhou, Xikun; Zhao, Wei; Cui, Jun; Wang, Helen Y.; Wang, Rong-Fu] Houston Methodist Res Inst, Ctr Inflammat & Epigenet, Houston, TX 77030 USA. [Chepelev, Iouri] Cincinnati Childrens Hosp Med Ctr, Ctr Autoimmune Genom & Etiol, Cincinnati, OH 45229 USA. [Wei, Gang] Chinese Acad Sci, Shanghai Inst Biol Sci, CAS MPG Partner Inst Computat Biol, Shanghai 200031, Peoples R China. [Zhao, Keji] NHLBI, Syst Biol Ctr, NIH, Bethesda, MD 20892 USA. RP Wang, RF (reprint author), Houston Methodist Res Inst, Ctr Inflammat & Epigenet, Houston, TX 77030 USA. EM rwang3@tmhs.org FU NIH [R01CA101795, R01CA090327]; GlaxoSmithKline FX We thank Dr Alexander Rudensky (Sloan-Kettering Institute, NY) for the Foxp3-GFP reporter mice, David Haviland (Houston Methodist Research Institute) for his assistance with the FACS analysis, and Jana S. Burchfield for editing the manuscript. This work is supported, in part, by grants from the NIH (R01CA101795, R01CA090327) and GlaxoSmithKline. NR 56 TC 21 Z9 21 U1 0 U2 4 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 DEC PY 2014 VL 5 AR 5780 DI 10.1038/ncomms6780 PG 15 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA AY5LI UT WOS:000347613200001 PM 25531312 ER PT J AU Citrin, DE Mitchell, JB AF Citrin, Deborah E. Mitchell, James B. TI Altering the Response to Radiation: Sensitizers and Protectors SO SEMINARS IN ONCOLOGY LA English DT Review ID IN-VIVO RADIOSENSITIZATION; HUMAN TUMOR-CELLS; IONIZING-RADIATION; RANDOMIZED-TRIAL; DNA-REPAIR; MOLECULAR-AGENTS; INDUCED FIBROSIS; PROSTATE-CANCER; GENE-EXPRESSION; NORMAL-TISSUES AB A number of agents are used clinically to enhance the efficacy of radiotherapy today, many of which are cytotoxic chemotherapies. Agents that enhance radiation induced tumor cell killing or protect normal tissues from the deleterious effects of ionizing radiation are collectively termed radiation modifiers. A significant effort in radiobiological research is geared towards describing and testing radiation modifiers with the intent of enhancing the therapeutic effects of radiation while minimizing normal tissue toxicity. In this review, we discuss the characteristics of these agents, the testing required to translate these agents into clinical trials, and highlight some challenges in these efforts. Published by Elsevier Inc. C1 NCI, Radiat Oncol Branch, Bethesda, MD 20892 USA. NCI, Radiat Biol Branch, Bethesda, MD 20892 USA. RP Citrin, DE (reprint author), NCI, Sect Translat Radiat Oncol, Radiat Oncol Branch, Bethesda, MD 20892 USA. EM citrind@mail.nih.gov FU Intramural Research Program of the National Institutes of Health; National Cancer Institute FX This research was supported by the Intramural Research Program of the National Institutes of Health, National Cancer Institute. NR 64 TC 3 Z9 3 U1 3 U2 9 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0093-7754 EI 1532-8708 J9 SEMIN ONCOL JI Semin. Oncol. PD DEC PY 2014 VL 41 IS 6 BP 848 EP 859 DI 10.1053/j.seminoncol.2014.09.013 PG 12 WC Oncology SC Oncology GA AY6CQ UT WOS:000347655600013 PM 25499642 ER PT J AU Snow, SJ McGee, J Miller, DB Bass, V Schladweiler, MC Thomas, RF Krantz, T King, C Ledbetter, AD Richards, J Weinstein, JP Conner, T Willis, R Linak, WP Nash, D Wood, CE Elmore, SA Morrison, JP Johnson, CL Gilmour, MI Kodavanti, UP AF Snow, Samantha J. McGee, John Miller, Desinia B. Bass, Virginia Schladweiler, Mette C. Thomas, Ronald F. Krantz, Todd King, Charly Ledbetter, Allen D. Richards, Judy Weinstein, Jason P. Conner, Teri Willis, Robert Linak, William P. Nash, David Wood, Charles E. Elmore, Susan A. Morrison, James P. Johnson, Crystal L. Gilmour, Matthew Ian Kodavanti, Urmila P. TI Inhaled Diesel Emissions Generated with Cerium Oxide Nanoparticle Fuel Additive Induce Adverse Pulmonary and Systemic Effects SO TOXICOLOGICAL SCIENCES LA English DT Article DE diesel exhaust; cerium oxide; cardiopulmonary; nanoparticle ID SPRAGUE-DAWLEY RATS; OXIDATIVE STRESS; EXHAUST INHALATION; INTRATRACHEAL INSTILLATION; PARTICULATE MATTER; PERIPHERAL-BLOOD; IMMUNE-RESPONSES; EXPOSURE; PARTICLES; CELLS AB Diesel exhaust (DE) exposure induces adverse cardiopulmonary effects. Cerium oxide nanoparticles added to diesel fuel (DECe) increases fuel burning efficiency but leads to altered emission characteristics and potentially altered health effects. Here, we evaluated whether DECe results in greater adverse pulmonary effects compared with DE. Male Sprague Dawley rats were exposed to filtered air, DE, or DECe for 5 h/day for 2 days. N-acetyl glucosaminidase activity was increased in bronchial alveolar lavage fluid (BALF) of rats exposed to DECe but not DE. There were also marginal but insignificant increases in several other lung injury biomarkers in both exposure groups (DECe>DE for all). To further characterize DECe toxicity, rats in a second study were exposed to filtered air or DECe for 5 h/day for 2 days or 4 weeks. Tissue analysis indicated a concentration-and time-dependent accumulation of lung and liver cerium followed by a delayed clearance. The gas-phase and high concentration of DECe increased lung inflammation at the 2-day time point, indicating that gas-phase components, in addition to particles, contribute to pulmonary toxicity. This effect was reduced at 4 weeks except for a sustained increase in BALF gamma-glutamyl transferase activity. Histopathology and transmission electron microscopy revealed increased alveolar septa thickness due to edema and increased numbers of pigmented macrophages after DECe exposure. Collectively, these findings indicate that DECe induces more adverse pulmonary effects on a mass basis than DE. In addition, lung accumulation of cerium, systemic translocation to the liver, and delayed clearance are added concerns to existing health effects of DECe. C1 [Snow, Samantha J.; Miller, Desinia B.] Univ N Carolina, Curriculum Toxicol, Chapel Hill, NC 27599 USA. [Snow, Samantha J.; McGee, John; Schladweiler, Mette C.; Thomas, Ronald F.; Krantz, Todd; King, Charly; Ledbetter, Allen D.; Richards, Judy; Gilmour, Matthew Ian; Kodavanti, Urmila P.] US EPA, Environm Publ Hlth Div, NHEERL, Res Triangle Pk, NC 27711 USA. [Bass, Virginia] Univ N Carolina, Gillings Sch Publ Hlth, Dept Environm Sci & Engn, Chapel Hill, NC 27599 USA. [Weinstein, Jason P.; Conner, Teri; Willis, Robert] US EPA, Environm Characterizat & Apportionment Branch, NERL, Res Triangle Pk, NC 27711 USA. [Linak, William P.; Nash, David] US EPA, Air Pollut Prevent & Control Div, NRMRL, Res Triangle Pk, NC 27711 USA. [Nash, David] Arcadis US Inc, Durham, NC 27713 USA. [Wood, Charles E.] US EPA, Integrated Syst Toxicol Div, NHEERL, Res Triangle Pk, NC 27711 USA. [Elmore, Susan A.] Natl Inst Environm Hlth Sci, Natl Toxicol Program Div, Res Triangle Pk, NC 27711 USA. [Morrison, James P.; Johnson, Crystal L.] Pathol Associates Inc, Charles River Labs, Durham, NC 27703 USA. RP Snow, SJ (reprint author), US EPA, Environm Publ Hlth Div, NHEERL, 109 TW Alexander Dr, Res Triangle Pk, NC 27711 USA. EM snow.samantha@epa.gov OI Bass, Virginia/0000-0001-6219-2448; Snow, Samantha/0000-0003-1812-8582 FU U.S. Environmental Protection Agency/University of North Carolina Toxicology [CR835152010]; U.S. Environmental Protection Agency Senior Environmental Employment Program; Division of the National Toxicology Program of the National Institutes of Health FX This work was supported by the U.S. Environmental Protection Agency/University of North Carolina Toxicology Training Agreement CR835152010 to S.J.S.; U.S. Environmental Protection Agency Senior Environmental Employment Program to R.F.T.; and the Division of the National Toxicology Program of the National Institutes of Health. NR 66 TC 7 Z9 8 U1 2 U2 22 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 1096-6080 EI 1096-0929 J9 TOXICOL SCI JI Toxicol. Sci. PD DEC PY 2014 VL 142 IS 2 BP 403 EP 417 DI 10.1093/toxsci/kfu187 PG 15 WC Toxicology SC Toxicology GA AY5MZ UT WOS:000347617800010 PM 25239632 ER PT J AU Ngalame, NNO Tokar, EJ Person, RJ Waalkes, MP AF Ngalame, Ntube N. O. Tokar, Erik J. Person, Rachel J. Waalkes, Michael P. TI Silencing KRAS Overexpression in Arsenic-Transformed Prostate Epithelial and Stem Cells Partially Mitigates Malignant Phenotype SO TOXICOLOGICAL SCIENCES LA English DT Article DE arsenic; prostate cells; stem cells; shRNA; KRAS; cancer ID RAS ONCOGENE ACTIVATION; MATRIX METALLOPROTEINASES; PANCREATIC-CANCER; K-RAS; THERAPY; STEM/PROGENITOR; STATISTICS; KNOCKDOWN; MUTATIONS; GROWTH AB Inorganic arsenic is a human carcinogen that likely targets the prostate. Chronic arsenic exposure malignantly transforms the RWPE-1 human prostate epithelial line to chronic arsenic exposed-prostate epithelial (CAsE-PE) cells, and a derivative normal prostate stem cell (SC) line, WPE-stem to arsenic-cancer SCs (As-CSCs). The KRAS oncogene is highly overexpressed in CAsE-PE cells and activation precedes transformation, inferring mechanistic significance. As-CSCs also highly overexpress KRAS. Thus, we hypothesize KRAS activation is key in causing and maintaining an arsenic-induced malignant phenotype, and hence, KRAS knockdown (KD) may reverse this malignant phenotype. RNA interference using shRNAmirs to obtain KRAS KD was used in CAsE-PE and As-CSC cells. Cells analyzed 2 weeks post transduction showed KRAS protein decreased to 5% of control after KD, confirming stable KD. KRAS KD decreased phosphorylated ERK, indicating inhibition of RAS/ERK signaling, a proliferation/survival pathway activated with arsenic transformation. Secreted metalloproteinase (MMP) activity was increased by arsenic-induced malignant transformation, but KRAS KD from 4 weeks on decreased secreted MMP-9 activity by 50% in As-CSCs. Colony formation, a characteristic of cancer cells, was decreased in both KRAS KD transformants. KRAS KD also decreased the invasive capacity of both cell types. KRAS KD decreased proliferation in As-CSCs, consistent with loss of rapid tumor growth. Genes predicted to impact cell proliferation (eg, Cyclin D1, p16, and p21) changed accordingly in both KD cell types. Thus, KRAS silencing impacts aspects of arsenic-induced malignant phenotype, inducing loss of many typical cancer characteristics particularly in As-CSCs. C1 [Ngalame, Ntube N. O.; Tokar, Erik J.; Person, Rachel J.; Waalkes, Michael P.] NIEHS, Inorgan Toxicol Grp, Natl Toxicol Program Lab, Div Natl Toxicol Program, Res Triangle Pk, NC 27709 USA. RP Waalkes, MP (reprint author), DNTP, Div Natl Toxicol Program, 111 TW Alexander Dr,MD E1-07, Res Triangle Pk, NC 27709 USA. EM waalkes@niehs.nih.gov FU National Institute of Environmental Health Sciences of the National Institutes of Health (NIH); National Toxicology Program (NTP) [ES 102925] FX The intramural program of the National Institute of Environmental Health Sciences of the National Institutes of Health (NIH), and the National Toxicology Program (NTP) under project ES 102925. NR 36 TC 8 Z9 9 U1 1 U2 5 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 1096-6080 EI 1096-0929 J9 TOXICOL SCI JI Toxicol. Sci. PD DEC PY 2014 VL 142 IS 2 BP 489 EP 496 DI 10.1093/toxsci/kfu201 PG 8 WC Toxicology SC Toxicology GA AY5MZ UT WOS:000347617800018 PM 25273566 ER PT J AU Kim, H Hofstetter, CR Hughes, S Irvin, VL Kang, S Hovell, MF AF Kim, Hyeongsu Hofstetter, C. Richard Hughes, Suzanne Irvin, Veronica L. Kang, Sunny Hovell, Melbourne F. TI Changes in and Factors Affecting Second-hand Smoke Exposure in Nonsmoking Korean Americans in California: A Panel Study SO ASIAN NURSING RESEARCH LA English DT Article DE follow-up; immigrants; Korean Americans; second-hand smoke exposure ID ENVIRONMENTAL TOBACCO-SMOKE; SECONDHAND SMOKE; UNITED-STATES; DESCENT; ADULTS; ACCULTURATION; SEOUL AB Purpose: We evaluated changes in and factors affecting second-hand smoke (SHS) exposure in a panel study of nonsmokers. Methods: This study was based on data from a larger study of tobacco use among a representative sample of adults of Korean descent residing in California. Participants included 846 males and 1,399 females who were nonsmokers at baseline (2005-2006) and at follow-up (2007-2009). Participants were selected by probability sampling and were interviewed by telephone. Results: At baseline, 50.0% were exposed to any SHS, and at follow-up 2 years later, 60.4% were exposed to any SHS (p < .001). SHS expbsure at baseline was associated with acculturation, employment, spousal smoking, and having a friend who smoked (p < .001). Employment, spousal smoking, and other family members smoking were associated with SHS at follow-up (p < .001). The odds ratio of SHS in the employed group declined from 2.01 at baseline to 1.53 at follow-up, that of the group having a smoking spouse increased from 1.88 to 2.36, and that of the group having other family members smoking increased from 1.20 to 1.69. Conclusions: We showed that SHS exposure increased among Korean American nonsmokers in California, and the most important variables explaining the change in SHS exposure involved smoking among others with whom the subject is associated. These findings could be used as objective evidence for developing public health policies to reduce SHS exposure. Copyright (c) 2014, Korean Society of Nursing Science. Published by Elsevier. All rights reserved. C1 [Kim, Hyeongsu] Konkuk Univ, Sch Med, Dept Prevent Med, Seoul 143701, South Korea. [Hofstetter, C. Richard] San Diego State Univ, Grad Sch Publ Hlth, Dept Polit Sci, San Diego, CA 92182 USA. [Hughes, Suzanne; Kang, Sunny; Hovell, Melbourne F.] San Diego State Univ, Grad Sch Publ Hlth, Ctr Behav Epidemiol & Community Hlth, San Diego, CA 92182 USA. [Irvin, Veronica L.] NIH, Ctr Clin, Dept Rehabil Med, Bethesda, MD 20892 USA. [Irvin, Veronica L.] Off Behav & Social Sci Res, Bethesda, MD USA. RP Kim, H (reprint author), Konkuk Univ, Sch Med, Dept Prevent Med, 120 Neungdong Ro, Seoul 143701, South Korea. EM mubul@kku.ac.kr NR 35 TC 1 Z9 1 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1976-1317 EI 2093-7482 J9 ASIAN NURS RES JI Asian Nurs. Res. PD DEC PY 2014 VL 8 IS 4 BP 313 EP 318 DI 10.1016/j.anr.2014.07.004 PG 6 WC Nursing SC Nursing GA AZ1OO UT WOS:000348008300012 PM 25529916 ER PT J AU Spagnolo, PA Ramchandani, VA Schwandt, ML Zhang, LS Blaine, SK Usala, JM Diamond, KA Phillips, MJ George, DT Momenan, R Heilig, M AF Spagnolo, Primavera A. Ramchandani, Vijay A. Schwandt, Melanie L. Zhang, Lishu Blaine, Sara K. Usala, Julie M. Diamond, Kristie A. Phillips, Monte J. George, David T. Momenan, Reza Heilig, Markus TI Effects of Naltrexone on Neural and Subjective Response to Alcohol in Treatment-Seeking Alcohol-Dependent Patients SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH LA English DT Article DE Alcoholism; Dopamine; Ventral Striatum; Naltrexone; Opioid System ID MU-OPIOID RECEPTOR; VENTRAL TEGMENTAL AREA; NUCLEUS-ACCUMBENS; DOPAMINE RELEASE; CUE REACTIVITY; KNOCKOUT MICE; ETHANOL; REWARD; MECHANISMS; RAT AB BackgroundPositively reinforcing properties of alcohol are in part mediated by activation of the ventral striatum (VS). Alcohol-induced release of endogenous opioids is thought to contribute to this response. Preclinical studies show that the opioid antagonist naltrexone (NTX) can block this cascade, but its ability to do so in treatment-seeking alcoholics has not been examined. Our objective was to study the effects of NTX on alcohol-induced VS activation and on amygdala response to affective stimuli in treatment-seeking alcohol-dependent inpatients. MethodsSixty-three treatment-seeking alcoholics were randomized to receive NTX (50mg) or placebo (PLC) daily. On Day 7, participants underwent an alcohol cue reactivity session, and craving was measured using the Penn Alcohol Craving Scale. On Day 9, participants received a saline infusion followed by an alcohol infusion and also viewed affective stimuli in a magnetic resonance scanner. ResultsIrrespective of medication treatment condition, the alcohol infusion did not activate the VS in the alcohol-dependent patients. Unexpectedly, VS activation was greater in NTX treated patients than in the PLC group. NTX treated patients also reported increased craving in response to alcohol cue exposure, and increased subjective response to alcohol (high and intoxicated) compared to PLC subjects. No significant effects of alcohol infusion on brain response to affective stimuli were in the NTX or PLC groups. ConclusionsUnlike previous findings in social drinkers, a moderate level of intoxication did not activate the VS in treatment-seeking alcoholics. This is likely to reflect tolerance to the positively reinforcing properties of alcohol in this clinical population. Our findings may help explain the efficacy of NTX to reduce heavy drinking, but not to maintain abstinence. C1 [Spagnolo, Primavera A.; Ramchandani, Vijay A.; Schwandt, Melanie L.; Zhang, Lishu; Blaine, Sara K.; Usala, Julie M.; Diamond, Kristie A.; Phillips, Monte J.; George, David T.; Momenan, Reza; Heilig, Markus] NIAAA, Lab Clin & Translat Studies, NIH, Bethesda, MD 20892 USA. RP Spagnolo, PA (reprint author), NIAAA, Lab Clin & Translat Studies, NIH, Clin Res Ctr, Bldg 10,10 Ctr Dr, Bethesda, MD 20892 USA. EM vera.spagnolo@nih.gov RI Schwandt, Melanie/L-9866-2016; OI Heilig, Markus/0000-0003-2706-2482 FU Division of Intramural Clinical and Biological Research, National Institute on Alcohol Abuse and Alcoholism, National Institutes of Health FX Supported by the Division of Intramural Clinical and Biological Research, National Institute on Alcohol Abuse and Alcoholism, National Institutes of Health. None of the authors has any conflict to disclose. NR 50 TC 3 Z9 3 U1 0 U2 4 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0145-6008 EI 1530-0277 J9 ALCOHOL CLIN EXP RES JI Alcoholism (NY) PD DEC PY 2014 VL 38 IS 12 BP 3024 EP 3032 DI 10.1111/acer.12581 PG 9 WC Substance Abuse SC Substance Abuse GA AY4IN UT WOS:000347541500019 PM 25581657 ER PT J AU Robinson, JC Graham, BB Rouault, TC Tuder, RM AF Robinson, Jeffrey C. Graham, Brian B. Rouault, Tracey C. Tuder, Rubin M. TI The Crossroads of Iron with Hypoxia and Cellular Metabolism Implications in the Pathobiology of Pulmonary Hypertension SO AMERICAN JOURNAL OF RESPIRATORY CELL AND MOLECULAR BIOLOGY LA English DT Review ID POSITRON-EMISSION-TOMOGRAPHY; ARTERIAL-HYPERTENSION; PLEXIFORM LESIONS; CHUVASH POLYCYTHEMIA; REGULATORY PROTEIN-1; DISTRIBUTION WIDTH; MESSENGER-RNA; HIF-ALPHA; DISEASE; DEFICIENCY AB The pathologic hallmark of pulmonary arterial hypertension (PAH) is pulmonary vascular remodeling, characterized by endothelial cell proliferation, smooth muscle hypertrophy, and perivascular inflammation, ultimately contributing to increased pulmonary arterial pressures. Several recent studies have observed that iron deficiency in patients with various forms of PAH is associated with worsened clinical outcome. Iron plays a key role in many cellular processes regulating the response to hypoxia, oxidative stress, cellular proliferation, and cell metabolism. Given the potential importance of iron supplementation in patients with the disease and the broad cellular functions of iron, we review its role in processes that pertain to PAH. C1 [Robinson, Jeffrey C.; Graham, Brian B.; Tuder, Rubin M.] Univ Colorado, Sch Med, Dept Med, Div Pulm Sci & Crit Care Med,Program Tradit Lung, Aurora, CO 80045 USA. [Rouault, Tracey C.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Program Mol Med, Bethesda, MD USA. RP Robinson, JC (reprint author), Univ Colorado, Sch Med, Dept Med, Div Pulm Sci & Crit Care Med,Program Tradit Lung, Aurora, CO 80045 USA. EM jeffrey.robinson@ucdenver.edu FU NHLBI NIH HHS [K08 HL105536] NR 92 TC 13 Z9 14 U1 0 U2 3 PU AMER THORACIC SOC PI NEW YORK PA 25 BROADWAY, 18 FL, NEW YORK, NY 10004 USA SN 1044-1549 EI 1535-4989 J9 AM J RESP CELL MOL JI Am. J. Respir. Cell Mol. Biol. PD DEC PY 2014 VL 51 IS 6 BP 721 EP 729 DI 10.1165/rcmb.2014-0021TR PG 9 WC Biochemistry & Molecular Biology; Cell Biology; Respiratory System SC Biochemistry & Molecular Biology; Cell Biology; Respiratory System GA AY2KS UT WOS:000347419700001 PM 24988529 ER PT J AU Martinu, T Gowdy, KM Nugent, JL Sun, J Kinnier, CV Nelson, ME Lyes, MA Kelly, FL Foster, WM Gunn, MD Palmer, SM AF Martinu, Tereza Gowdy, Kymberly M. Nugent, Julia L. Sun, Jesse Kinnier, Christine V. Nelson, Margaret E. Lyes, Matthew A. Kelly, Francine L. Foster, W. Michael Gunn, Michael D. Palmer, Scott M. TI Role of C-C Motif Ligand 2 and C-C Motif Receptor 2 in Murine Pulmonary Graft-versus-Host Disease after Lipopolysaccharide Inhalations SO AMERICAN JOURNAL OF RESPIRATORY CELL AND MOLECULAR BIOLOGY LA English DT Article DE graft-versus-host disease; lipopolysaccharide; dendritic cells; C-C motif ligand 2; C-C motif receptor 2 ID CHEMOATTRACTANT PROTEIN-1 MCP-1; IDIOPATHIC PNEUMONIA SYNDROME; STEM-CELL TRANSPLANTATION; INNATE IMMUNE ACTIVATION; DENDRITIC CELLS; LUNG INJURY; AIRWAY HYPERRESPONSIVENESS; INHALED LIPOPOLYSACCHARIDE; CHEMOKINE RECEPTOR-2; CCR2(-/-) MICE AB Environmental exposures are a potential trigger of chronic pulmonary graft-versus-host disease (pGVHD) after successful recovery from hematopoietic cell transplant (HCT). We hypothesized that inhalations of LPS, a prototypic environmental stimulus, trigger pGVHD via increased pulmonary recruitment of donor-derived antigen-presenting cells (APCs) through the C-C motif ligand 2 (CCL2)-C-C motif receptor 2 (CCR2) chemokine axis. B10.BR(H2(k)) and C57BL/6(H2(b)) mice underwent allogeneic (Allo) or syngeneic (Syn) HCT with wild-type (WT) C57BL/6, CCL2(-/-), or CCR2(-/-) donors. After 4 weeks, recipient mice received daily inhaled LPS for 5 days and were killed at multiple time points. Allo mice exposed to repeated inhaled LPS developed prominent lymphocytic bronchiolitis, similar to human pGVHD. The increase in pulmonary T cells in Allo mice after LPS exposures was accompanied by increased CCL2, CCR2, and Type-1 T-helper cytokines as well as by monocytes and monocytederived dendritic cells (moDCs) compared with Syn and nontransplanted controls. Using CCL2(-/-) donors leads to a significant decrease in lungDCs but to only mildly reduced CD4 T cells. Using CCR2(-/-) donors significantly reduces lung DCs and moDCs but does not change T cells. CCL2 or CCR2 deficiency does not alter pGVHD pathology but increases airway hyperreactivity and IL-5 or IL-13 cytokines. Our results show that hematopoietic donor- derived CCL2 and CCR2 regulate recruitment of APCs to the Allo lung after LPS exposure. Although they do not alter pathologic pGVHD, their absence is associated with increased airway hyperreactivity and IL-5 and IL-13 cytokines. These results suggest that the APC changes that result from CCL2-CCR2 blockade may have unexpected effects on T cell differentiation and physiologic outcomes in HCT. C1 [Martinu, Tereza; Nelson, Margaret E.; Lyes, Matthew A.; Kelly, Francine L.; Foster, W. Michael; Gunn, Michael D.; Palmer, Scott M.] Duke Univ, Med Ctr, Dept Med, Durham, NC 27710 USA. [Palmer, Scott M.] Duke Univ, Med Ctr, Duke Clin Res Inst, Durham, NC 27710 USA. [Gowdy, Kymberly M.] Natl Inst Environm Hlth Sci, Res Triangle Pk, NC USA. [Nugent, Julia L.; Sun, Jesse] Univ N Carolina, Sch Med, Chapel Hill, NC USA. [Kinnier, Christine V.] Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA. RP Martinu, T (reprint author), Duke Univ, Med Ctr, DUMC Box 3221, Durham, NC 27710 USA. EM tereza.martinu@duke.edu FU National Institutes of Health [S10RR019145] FX The authors thank Mr. Robert F. Beasley for help with lung DC isolation. Flow cytometric sorting was performed in the Duke Human Vaccine Institute Research Flow Cytometry Shared Resource Facility (Durham, NC) supported by National Institutes of Health grant S10RR019145. NR 36 TC 1 Z9 1 U1 0 U2 3 PU AMER THORACIC SOC PI NEW YORK PA 25 BROADWAY, 18 FL, NEW YORK, NY 10004 USA SN 1044-1549 EI 1535-4989 J9 AM J RESP CELL MOL JI Am. J. Respir. Cell Mol. Biol. PD DEC PY 2014 VL 51 IS 6 BP 810 EP 821 DI 10.1165/rcmb.2013-0451OC PG 12 WC Biochemistry & Molecular Biology; Cell Biology; Respiratory System SC Biochemistry & Molecular Biology; Cell Biology; Respiratory System GA AY2KS UT WOS:000347419700010 PM 24921973 ER PT J AU Leja, M You, WC Camargo, MC Saito, H AF Leja, Marcis You, Weicheng Camargo, M. Constanza Saito, Hiroshi TI Implementation of gastric cancer screening - The global experience SO BEST PRACTICE & RESEARCH IN CLINICAL GASTROENTEROLOGY LA English DT Article DE Biomarkers; Gastric cancer; Helicobacter pylori; Precancerous lesions; Screening ID HELICOBACTER-PYLORI ERADICATION; SERUM PEPSINOGEN; STOMACH-CANCER; HIGH-RISK; COST-EFFECTIVENESS; FOLLOW-UP; PRECANCEROUS LESIONS; MULTIPLEX SEROLOGY; GENE POLYMORPHISMS; CHINESE POPULATION AB Gastric cancer (GC) is still an important global healthcare problem, and in absolute figures it is going to remain at the present level in foreseeable future. In general, survival' of patients with GC is poor mainly due to advanced-stage diagnosis. Early-stage GC can be cured by endoscopic resection or less invasive surgical treatment. Unfortunately, there is no appropriate screening strategy available for global application. This article provides a description of established national and regional GC screening programs and the screening modalities used. This review also summarizes current approaches to develop cancer-screening biomarkers. Although candidates with initial promising results have been suggested, moving discovery into clinical practice is still a major challenge. Well-designed biomarker studies, with systematic validation steps, are needed to decrease the burden of this fatal disease. (C) 2014 Elsevier Ltd. All rights reserved. C1 [Leja, Marcis] Univ Latvia, Fac Med, LV-1006 Riga, Latvia. [You, Weicheng] Peking Univ Canc Hosp & Inst, Dept Canc Epidemiol, Key Lab Carcinogenesis & Translat Res, Minist Educ, Beijing 100142, Peoples R China. [Camargo, M. Constanza] NCI, Div Canc Epidemiol & Genet, Rockville, MD USA. [Saito, Hiroshi] Natl Canc Ctr, Res Ctr Canc Prevent & Detect, Canc Screening Assessment & Management Div, Tokyo 1040045, Japan. RP Leja, M (reprint author), Univ Latvia, Fac Med, 6 Linezera Iela, LV-1006 Riga, Latvia. EM cei@latnet.lv; weichengyou@yahoo.com; camargomc@mail.nih.gov; hrsaito@ncc.go.jp RI Camargo, M. Constanza/R-9891-2016 FU National Research Program in Public Health priority [4] FX ML has been supported in part for writing of the manuscript from the project No. 4 'Evaluation of the possibilities to decrease the gastric cancer caused mortality in Latvia' within the National Research Program in Public Health priority. NR 95 TC 8 Z9 9 U1 1 U2 12 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 1521-6918 EI 1532-1916 J9 BEST PRACT RES CL GA JI Best Pract. Res. Clin. Gastroenterol. PD DEC PY 2014 VL 28 IS 6 BP 1093 EP 1106 DI 10.1016/j.bpg.2014.09.005 PG 14 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA AY1PK UT WOS:000347364500013 PM 25439074 ER PT J AU Soubias, O Teague, WE Hines, KG Gawrisch, K AF Soubias, Olivier Teague, Walter E. Hines, Kirk G. Gawrisch, Klaus TI The role of membrane curvature elastic stress for function of rhodopsin-like G protein-coupled receptors SO BIOCHIMIE LA English DT Review DE G protein-coupled membrane receptor; Rhodopsin; Membrane; Lipid; Cholesterol ID ACTIVATION; TRANSDUCIN; NETWORKS; SEQUENCE; DISTANCE; BILAYERS AB The human genome encodes about 800 different G protein-coupled receptors (GPCR). They are key molecules in signal transduction pathways that transmit signals of a variety of ligands such as hormones and neurotransmitters to the cell interior. Upon ligand binding, the receptors undergo structural transitions that either enhance or inhibit transmission of a specific signal to the cell interior. Here we discuss results which indicate that transmission of such signals can be strongly modulated by the composition of the lipid matrix into which GPCR are imbedded. Experimental results have been obtained on rhodopsin, a prototype GPCR whose structure and function is representative for the great majority of GPCR in humans. The data shed light on the importance of curvature elastic stress in the lipid domain for function of GPCR. (C) Published by Elsevier B.V. C1 [Soubias, Olivier; Teague, Walter E.; Hines, Kirk G.; Gawrisch, Klaus] Natl Inst Alcohol & Alcoholism, Lab Membrane Biochem & Biophys, NIH, Bethesda, MD 20892 USA. RP Gawrisch, K (reprint author), Natl Inst Alcohol & Alcoholism, Lab Membrane Biochem & Biophys, NIH, Bethesda, MD 20892 USA. EM klausg@mail.nih.gov FU Intramural Research Program of the National Institute on Alcohol Abuse and Alcoholism, National Institutes of Health FX This work was supported by the Intramural Research Program of the National Institute on Alcohol Abuse and Alcoholism, National Institutes of Health. NR 28 TC 5 Z9 5 U1 2 U2 21 PU ELSEVIER FRANCE-EDITIONS SCIENTIFIQUES MEDICALES ELSEVIER PI PARIS PA 23 RUE LINOIS, 75724 PARIS, FRANCE SN 0300-9084 EI 1638-6183 J9 BIOCHIMIE JI Biochimie PD DEC PY 2014 VL 107 BP 28 EP 32 DI 10.1016/j.biochi.2014.10.011 PN A PG 5 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA AY6FA UT WOS:000347661500006 PM 25447139 ER PT J AU Natarajan, B Salahuddin, T Sadek, A Dave, J Nanda, N Le, B Reddy, A Gelfand, J Mehta, N AF Natarajan, B. Salahuddin, T. Sadek, A. Dave, J. Nanda, N. Le, B. Reddy, A. Gelfand, J. Mehta, N. TI In vivo characterization of vascular diseases in psoriasis through implementation of a multimodal imaging program SO BRITISH JOURNAL OF DERMATOLOGY LA English DT Meeting Abstract CT 7th International Congress of Psoriasis - From Gene to Clinic CY DEC 11-13, 2014 CL London, ENGLAND C1 [Natarajan, B.; Salahuddin, T.; Sadek, A.; Dave, J.; Nanda, N.; Le, B.; Reddy, A.; Mehta, N.] NIH, Bethesda, MD 20892 USA. [Gelfand, J.] Univ Penn, Philadelphia, PA 19104 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0007-0963 EI 1365-2133 J9 BRIT J DERMATOL JI Br. J. Dermatol. PD DEC PY 2014 VL 171 IS 6 MA FC24 BP E116 EP E116 PG 1 WC Dermatology SC Dermatology GA AX9QD UT WOS:000347236100025 ER PT J AU Filer, D Patisaul, HB Schug, T Reif, D Thayer, K AF Filer, Dayne Patisaul, Heather B. Schug, Thaddeus Reif, David Thayer, Kristina TI Test driving ToxCast: endocrine profiling for 1858 chemicals included in phase II SO CURRENT OPINION IN PHARMACOLOGY LA English DT Article ID PROTECTION AB Identifying chemicals, beyond those already implicated, to test for potential endocrine disruption is a challenge and high throughput approaches have emerged as a potential tool for this type of screening. This review focused the Environmental Protection Agency's (EPA) ToxCast (TM) high throughput in vitro screening (HTS) program. Utility for identifying compounds was assessed and reviewed by using it to run the recently expanded chemical library (from 309 compounds to 1858) through the ToxPi (TM) prioritization scheme for endocrine disruption. The analysis included metabolic and neuroendocrine targets. This investigative approach simultaneously assessed the utility of ToxCast, and helped identify novel chemicals which may have endocrine activity. Results from this exercise suggest the spectrum of environmental chemicals with potential endocrine activity is much broader than indicated, and that some aspects of endocrine disruption are not fully covered in ToxCast. C1 [Filer, Dayne] US EPA, Natl Ctr Computat Toxicol, Off Res & Dev, Res Triangle Pk, NC 27709 USA. [Patisaul, Heather B.] N Carolina State Univ, Dept Biol Sci, Ctr Human Hlth & Environm, Raleigh, NC 27695 USA. [Schug, Thaddeus] NIEHS, Div Extramural Res, NIH, Dept Hlth & Human Serv, Morrisville, NC 27560 USA. [Reif, David] N Carolina State Univ, Bioinformat Res Ctr, Dept Biol Sci, Raleigh, NC 27695 USA. [Thayer, Kristina] NIEHS, Off Hlth Assessment & Translat, Div Natl Toxicol Program, NIH,Dept Hlth & Human Serv, Morrisville, NC 27560 USA. RP Thayer, K (reprint author), NIEHS, Off Hlth Assessment & Translat, Div Natl Toxicol Program, NIH,Dept Hlth & Human Serv, 530 Davis Dr,Room 2150 Mail Drop K2-04, Morrisville, NC 27560 USA. EM thayer@niehs.nih.gov OI Reif, David/0000-0001-7815-6767 FU Intramural NIH HHS [ZIA ES103226-01] NR 16 TC 13 Z9 13 U1 3 U2 14 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 1471-4892 EI 1471-4973 J9 CURR OPIN PHARMACOL JI Curr. Opin. Pharmacol. PD DEC PY 2014 VL 19 BP 145 EP 152 DI 10.1016/j.coph.2014.09.021 PG 8 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA AY3UO UT WOS:000347508000023 PM 25460227 ER PT J AU Shaughnessy, DT McAllister, K Worth, L Haugen, AC Meyer, JN Domann, FE Van Houten, B Mostoslavsky, R Bultman, SJ Baccarelli, AA Begley, TJ Sobol, RW Hirschey, MD Ideker, T Santos, JH Copeland, WC Tice, RR Balshaw, DM Tyson, FL AF Shaughnessy, Daniel T. McAllister, Kimberly Worth, Leroy Haugen, Astrid C. Meyer, Joel N. Domann, Frederick E. Van Houten, Bennett Mostoslavsky, Raul Bultman, Scott J. Baccarelli, Andrea A. Begley, Thomas J. Sobol, Robert W. Hirschey, Matthew D. Ideker, Trey Santos, Janine H. Copeland, William C. Tice, Raymond R. Balshaw, David M. Tyson, Frederick L. TI Mitochondria, Energetics, Epigenetics, and Cellular Responses to Stress SO ENVIRONMENTAL HEALTH PERSPECTIVES LA English DT Review ID DNA COPY NUMBER; PLURIPOTENT STEM-CELLS; COLON-CARCINOMA CELLS; ENERGY-METABOLISM; EXCISION-REPAIR; OXIDATIVE-PHOSPHORYLATION; ATAXIA-TELANGIECTASIA; HISTONE ACETYLATION; BUTYRATE METABOLISM; CANCER METABOLISM AB Background: Cells respond to environmental stressors through several key pathways, including response to reactive oxygen species (ROS), nutrient and ATP sensing, DNA damage response (DDR), and epigenetic alterations. Mitochondria play a central role in these pathways not only through energetics and ATP production but also through metabolites generated in the tricarboxylic acid cycle, as well as mitochondria-nuclear signaling related to mitochondria morphology, biogenesis, fission/fusion, mitophagy, apoptosis, and epigenetic regulation. Objectives: We investigated the concept of bidirectional interactions between mitochondria and cellular pathways in response to environmental stress with a focus on epigenetic regulation, and we examined DNA repair and DDR pathways as examples of biological processes that respond to exogenous insults through changes in homeostasis and altered mitochondrial function. Methods: The National Institute of Environmental Health Sciences sponsored the Workshop on Mitochondria, Energetics, Epigenetics, Environment, and DNA Damage Response on 25-26 March 2013. Here, we summarize key points and ideas emerging from this meeting. Discussion: A more comprehensive understanding of signaling mechanisms (cross-talk) between the mitochondria and nucleus is central to elucidating the integration of mitochondrial functions with other cellular response pathways in modulating the effects of environmental agents. Recent studies have highlighted the importance of mitochondrial functions in epigenetic regulation and DDR with environmental stress. Development and application of novel technologies, enhanced experimental models, and a systems-type research approach will help to discern how environmentally induced mitochondrial dysfunction affects key mechanistic pathways. Conclusions: Understanding mitochondria-cell signaling will provide insight into individual responses to environmental hazards, improving prediction of hazard and susceptibility to environmental stressors. C1 [Shaughnessy, Daniel T.; McAllister, Kimberly; Worth, Leroy; Haugen, Astrid C.; Balshaw, David M.; Tyson, Frederick L.] NIEHS, Div Extramural Res & Training, NIH, Dept Hlth & Human Serv, Res Triangle Pk, NC 27709 USA. [Meyer, Joel N.] Duke Univ, Nicholas Sch Environm, Durham, NC 27708 USA. [Domann, Frederick E.] Univ Iowa, Carver Coll Med, Dept Radiat Oncol, Free Radical & Radiat Biol Program, Iowa City, IA USA. [Van Houten, Bennett; Sobol, Robert W.] Univ Pittsburgh, Inst Canc, Hillman Canc Ctr, Pittsburgh, PA USA. [Mostoslavsky, Raul] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Canc, Boston, MA USA. [Bultman, Scott J.] Univ N Carolina, Dept Genet, Chapel Hill, NC USA. [Baccarelli, Andrea A.] Harvard Univ, Sch Publ Hlth, Exposure Epidemiol & Risk Program, Lab Environm Epigenet, Boston, MA 02115 USA. [Begley, Thomas J.] SUNY Albany, Coll Nanoscale Sci & Engn, Albany, NY 12222 USA. [Sobol, Robert W.] Univ Pittsburgh, Sch Med, Dept Pharmacol & Chem Biol, Pittsburgh, PA USA. [Hirschey, Matthew D.] Duke Univ, Med Ctr, Durham, NC USA. [Ideker, Trey] Univ Calif San Diego, Dept Med, La Jolla, CA 92093 USA. [Ideker, Trey] Univ Calif San Diego, Dept Bioengn, La Jolla, CA 92093 USA. [Santos, Janine H.] NIEHS, Mol Carcinogenesis Lab, NIH, DHHS, Res Triangle Pk, NC 27709 USA. [Copeland, William C.] NIEHS, Mol Genet Lab, NIH, DHHS, Res Triangle Pk, NC 27709 USA. [Tice, Raymond R.] NIEHS, Biomol Screening Branch, Div Natl Toxicol Program, NIH,DHHS, Res Triangle Pk, NC 27709 USA. RP Shaughnessy, DT (reprint author), NIEHS, Div Extramural Res & Training, MD K3-12,POB 12233, Res Triangle Pk, NC 27709 USA. EM shaughn1@niehs.nih.gov OI Baccarelli, Andrea/0000-0002-3436-0640; Domann, Frederick/0000-0002-0489-2179 FU NIA NIH HHS [R01 AG045351]; NIEHS NIH HHS [R01 ES017540, P30 ES005605, P42 ES010356] NR 105 TC 35 Z9 35 U1 7 U2 55 PU US DEPT HEALTH HUMAN SCIENCES PUBLIC HEALTH SCIENCE PI RES TRIANGLE PK PA NATL INST HEALTH, NATL INST ENVIRONMENTAL HEALTH SCIENCES, PO BOX 12233, RES TRIANGLE PK, NC 27709-2233 USA SN 0091-6765 EI 1552-9924 J9 ENVIRON HEALTH PERSP JI Environ. Health Perspect. PD DEC PY 2014 VL 122 IS 12 BP 1271 EP 1278 DI 10.1289/ehp.1408418 PG 8 WC Environmental Sciences; Public, Environmental & Occupational Health; Toxicology SC Environmental Sciences & Ecology; Public, Environmental & Occupational Health; Toxicology GA AY1YC UT WOS:000347384600012 PM 25127496 ER PT J AU Chia, R Haddock, S Beilina, A Rudenko, IN Mamais, A Kaganovich, A Li, Y Kumaran, R Nalls, MA Cookson, MR AF Chia, Ruth Haddock, Sara Beilina, Alexandra Rudenko, Iakov N. Mamais, Adamantios Kaganovich, Alice Li, Yan Kumaran, Ravindran Nalls, Michael A. Cookson, Mark R. TI Phosphorylation of LRRK2 by casein kinase 1 alpha regulates trans-Golgi clustering via differential interaction with ARHGEF7 SO NATURE COMMUNICATIONS LA English DT Article ID PARKINSONS-DISEASE; CYTOPLASMIC LOCALIZATION; 14-3-3 BINDING; PROTEIN; INHIBITION; MUTATION; MUTANT; RISK AB LRRK2, a gene relevant to Parkinson's disease, encodes a scaffolding protein with both GTPase and kinase activities. LRRK2 protein is itself phosphorylated and therefore is subject to regulation by cell signalling; however, the kinase(s) responsible for this event have not been definitively identified. Here using an unbiased siRNA kinome screen, we identify and validate casein kinase 1 alpha (CK1 alpha) as being responsible for LRRK2 phosphorylation, including in the adult mouse striatum. We further show that LRRK2 recruitment to TGN46-positive Golgi-derived vesicles is modulated by constitutive LRRK2 phosphorylation by CK1 alpha. These effects are mediated by differential protein interactions of LRRK2 with a guanine nucleotide exchange factor, ARHGEF7. These pathways are therefore likely involved in the physiological maintenance of the Golgi in cells, which may play a role in the pathogenesis of Parkinson's disease. C1 [Chia, Ruth; Haddock, Sara; Beilina, Alexandra; Rudenko, Iakov N.; Mamais, Adamantios; Kaganovich, Alice; Kumaran, Ravindran; Cookson, Mark R.] NIA, Cell Biol & Gene Express Sect, Neurogenet Lab, Bethesda, MD 20892 USA. [Nalls, Michael A.] NIA, Mol Genet Sect, Neurogenet Lab, Bethesda, MD 20892 USA. [Li, Yan] NINDS, Peptide Sequencing Facil, NIH, Bethesda, MD 20892 USA. RP Cookson, MR (reprint author), NIA, Cell Biol & Gene Express Sect, Neurogenet Lab, 35 Convent Dr, Bethesda, MD 20892 USA. EM cookson@mail.nih.gov FU National Institute on Aging, National Institutes of Health; Bachmann-Strauss Dystonia and Parkinson Foundation REP FX This work was supported by the Intramural Research Programme of the National Institute on Aging, National Institutes of Health and the Bachmann-Strauss Dystonia and Parkinson Foundation RFP 2012. We thank our laboratory colleagues for their support, advice and critical reading of the manuscript. We would also like to thank Dr Jean-Marc Taymans, Leuven, for the gift of stable FLAG-tagged LRRK2 cell lines and Dr Dario Alessi, Dundee, for antibodies and access to LRRK2-IN1. NR 43 TC 16 Z9 16 U1 2 U2 6 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 2041-1723 J9 NAT COMMUN JI Nat. Commun. PD DEC PY 2014 VL 5 AR 5827 DI 10.1038/ncomms6827 PG 11 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA AY5LU UT WOS:000347614400002 PM 25500533 ER PT J AU Maleth, J Choi, S Muallem, S Ahuja, M AF Maleth, Jozsef Choi, Seok Muallem, Shmuel Ahuja, Malini TI Translocation between PI(4,5)P-2-poor and PI(4,5)P-2-rich microdomains during store depletion determines STIM1 conformation and Orai1 gating SO NATURE COMMUNICATIONS LA English DT Article ID FAST CA2+-DEPENDENT INACTIVATION; STROMAL INTERACTION MOLECULE-1; CRAC CHANNELS; CALCIUM-ENTRY; DOMAIN; ACTIVATION; PROTEINS; ER; PHOSPHOINOSITIDES; STIM1-ORAI1 AB The Orai1-STIM1 current undergoes slow Ca2+-dependent inactivation (SCDI) mediated by the binding of SARAF to STIM1. Here we report the use of SCDI by SARAF as a probe of the conformation and microdomain localization of the Orai1-STIM1 complex. We find that the interaction of STIM1 with Orai1 carboxyl terminus (C terminus) and the STIM1 K-domain are required for the interaction of SARAF with STIM1 and SCDI. STIM1-Orai1 must be in a PM/ER microdomain tethered by E-Syt1, stabilized by septin4 and enriched in PI(4,5)P-2 for STIM1-SARAF interaction. Targeting STIM1 to PI(4,5)P-2-rich and -poor microdomains reveals that SARAF-dependent SCDI is observed only when STIM1-Orai1 are within the PI(4,5)P-2-rich microdomain. Notably, store depletion results in transient localization of STIM1-Orai1 in the PI(4,5)P-2-poor microdomain, which then translocates to the PI(4,5)P-2-rich domain. These findings reveal the role of PM/ER tethers in the regulation of Orai1 function and a mode of regulation by PI(4,5)P-2 involving translocation between PI(4,5)P-2 microdomains. C1 [Maleth, Jozsef; Choi, Seok; Muallem, Shmuel; Ahuja, Malini] NIDCR, Epithelial Signaling & Transport Sect, Mol Physiol & Therapeut Branch, NIH, Bethesda, MD 20892 USA. [Maleth, Jozsef] Univ Szeged, Dept Med 1, H-6725 Szeged, Hungary. [Choi, Seok] Chosun Univ, Coll Med, Dept Physiol, Chosun 501375, South Korea. RP Muallem, S (reprint author), NIDCR, Epithelial Signaling & Transport Sect, Mol Physiol & Therapeut Branch, NIH, Bethesda, MD 20892 USA. EM shmuel.muallem@nih.gov FU NIH/NIDCR intramural grant [DE000735] FX We thank Drs Pietro De Camilli (Yale) for providing the E-Syt1, E-Syt2 and E-Syt3 plasmids and Jen Liou (UT Southwestern Medical center, Dallas) for providing E-Syt1. We thank Dr Tamas Balla for valuable discussions and suggestions and for providing the PI(4,5)P2 depletion system. This work was supported by the NIH/NIDCR intramural grant DE000735 to S. M. NR 39 TC 21 Z9 21 U1 0 U2 6 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 2041-1723 J9 NAT COMMUN JI Nat. Commun. PD DEC PY 2014 VL 5 AR 5843 DI 10.1038/ncomms6843 PG 10 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA AY6NF UT WOS:000347682200004 PM 25517631 ER PT J AU Yong, RL Yang, CZ Lu, J Wang, HE Schlaff, CD Tandle, A Graves, CA Elkahloun, AG Chen, XY Zhuang, ZP Lonser, RR AF Yong, Raymund L. Yang, Chunzhang Lu, Jie Wang, Huaien Schlaff, Cody D. Tandle, Anita Graves, Christian A. Elkahloun, Abdel G. Chen, Xiaoyuan Zhuang, Zhengping Lonser, Russell R. TI Cell transcriptional state alters genomic patterns of DNA double-strand break repair in human astrocytes SO NATURE COMMUNICATIONS LA English DT Article ID RECURRENT CHROMOSOMAL TRANSLOCATIONS; CHILDHOOD-CANCER SURVIVOR; SPINAL-CORD-INJURY; GENE FUSIONS; IONIZING-RADIATION; REACTIVE GLIOSIS; GLIAL-CELLS; EXPRESSION; GAMMA-H2AX; GLIOBLASTOMA AB The misrepair of DNA double-strand breaks in close spatial proximity within the nucleus can result in chromosomal rearrangements that are important in the pathogenesis of haematopoietic and solid malignancies. It is unknown why certain epigenetic states, such as those found in stem or progenitor cells, appear to facilitate neoplastic transformation. Here we show that altering the transcriptional state of human astrocytes alters patterns of DNA damage repair from ionizing radiation at a gene locus-specific and genome-wide level. Astrocytes induced into a reactive state exhibit increased DNA repair, compared with non-reactive cells, in actively transcribed chromatin after irradiation. In mapping these repair sites, we identify misrepair events and repair hotspots that are unique to each state. The precise characterization of genomic regions susceptible to mutation in specific transcriptional states provides new opportunities for addressing clonal evolution in solid cancers, in particular those where double-strand break induction is a cornerstone of clinical intervention. C1 [Yong, Raymund L.; Wang, Huaien] Icahn Sch Med Mt Sinai, Dept Neurosurg, New York, NY 10029 USA. [Yong, Raymund L.; Yang, Chunzhang; Lu, Jie; Zhuang, Zhengping; Lonser, Russell R.] NINDS, Surg Neurol Branch, NIH, Bethesda, MD 20892 USA. [Lu, Jie; Chen, Xiaoyuan] Natl Inst Biomed Imaging & Bioengn, Lab Mol Imaging & Nanomed, NIH, Bethesda, MD 20892 USA. [Schlaff, Cody D.; Tandle, Anita; Graves, Christian A.] NCI, Radiat Oncol Branch, NIH, Bethesda, MD 20892 USA. [Elkahloun, Abdel G.] NHGRI, Canc Genet Branch, NIH, Bethesda, MD 20892 USA. [Lonser, Russell R.] Ohio State Univ, Wexner Med Ctr, Dept Neurol Surg, Columbus, OH 43210 USA. RP Yong, RL (reprint author), Icahn Sch Med Mt Sinai, Dept Neurosurg, 1463 Madison Ave,Box 1136, New York, NY 10029 USA. EM raymund.yong@mountsinai.org; russell.lonser@osumc.edu FU NINDS; NCI; NHGRI; Radiology and Imaging Sciences Department, NIH Clinical Center; NIBIB FX We thank P. Gallant, I. Gordon, R. Hanson, B. Ikejiri, S. Pack and K. Camphausen for discussions and support, and K. Johnson for bioinformatics assistance. This work was funded by the Intramural Research Programs of NINDS, NCI and NHGRI. J.L. is in an Imaging Sciences Training Fellowship jointly supported by the Radiology and Imaging Sciences Department, NIH Clinical Center and the Intramural Research Program of NIBIB. NR 56 TC 4 Z9 5 U1 1 U2 12 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 DEC PY 2014 VL 5 AR 5799 DI 10.1038/ncomms6799 PG 12 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA AY5LL UT WOS:000347613500005 PM 25517576 ER PT J AU Metti, AL Yaffe, K Boudreau, RM Simonsick, EM Carnahan, RM Satterfield, S Harris, TB Ayonayon, HN Rosano, C Cauley, JA AF Metti, Andrea L. Yaffe, Kristine Boudreau, Robert M. Simonsick, Eleanor M. Carnahan, Ryan M. Satterfield, Suzanne Harris, Tamara B. Ayonayon, Hilsa N. Rosano, Caterina Cauley, Jane A. CA Hlth ABC Study TI Trajectories of inflammatory markers and cognitive decline over 10 years SO NEUROBIOLOGY OF AGING LA English DT Article DE Inflammatory markers; Cognitive decline; C-reactive protein; Interleukin-6 ID C-REACTIVE PROTEIN; ALZHEIMERS-DISEASE; OLDER-ADULTS; CARDIOVASCULAR HEALTH; HEART-DISEASE; RISK; DEMENTIA; ATHEROSCLEROSIS; INTERLEUKIN-6; ASSOCIATION AB We aimed to examine trajectories of inflammatory markers and cognitive decline over 10 years. Cox proportional hazards models were used to examine the association between interleukin-6 and C-reactive protein (CRP) trajectory components (slope, variability, and baseline level) and cognitive decline among 1323 adults, aged 70-79 years in the Health, Aging, and Body Composition Study. We tested for interactions by sex and apolipoprotein E (APOE) genotype. In models adjusted for multiple covariates and comorbidities, extreme CRP variability was significantly associated with cognitive decline (hazard ratio [HR] 1.6, 95% confidence interval [CI]: 1.1-2.3). This association was modified by sex and APOE e4 (p < 0.001 for both), such that the association remained among women (HR = 1.8; 95% CI: 1.1, 3.0) and among those with no APOE e4 allele (HR = 1.6; 95% CI: 1.1, 2.5). There were no significant associations between slope or baseline level of CRP and cognitive decline nor between interleukin-6 and cognitive decline. We believe CRP variability likely reflects poor control of or greater changes in vascular or metabolic disease over time, which in turn is associated with cognitive decline. (C) 2014 Elsevier Inc. All rights reserved. C1 [Metti, Andrea L.; Boudreau, Robert M.; Rosano, Caterina; Cauley, Jane A.] Univ Pittsburgh, Grad Sch Publ Hlth, Dept Epidemiol, Pittsburgh, PA 15213 USA. [Yaffe, Kristine] Univ Calif San Francisco, Dept Psychiat, San Francisco, CA USA. [Yaffe, Kristine] Univ Calif San Francisco, Dept Neurol, San Francisco, CA USA. [Yaffe, Kristine; Ayonayon, Hilsa N.] Univ Calif San Francisco, Dept Epidemiol & Biostat, San Francisco, CA 94143 USA. [Simonsick, Eleanor M.] NIA, Clin Res Branch, Baltimore, MD 21224 USA. [Carnahan, Ryan M.] Univ Iowa, Coll Publ Hlth, Dept Epidemiol, Iowa City, IA USA. [Satterfield, Suzanne] Univ Tennessee, Dept Prevent Med, Memphis, TN USA. [Harris, Tamara B.] NIA, Lab Epidemiol & Populat Sci, Intramural Res Program, Bethesda, MD 20892 USA. RP Metti, AL (reprint author), Univ Pittsburgh, Grad Sch Publ Hlth, Dept Epidemiol, Ctr Aging & Populat Hlth, 130 N Bellefield,Fourth Floor 456, Pittsburgh, PA 15213 USA. EM alw111@pitt.edu RI Cauley, Jane/N-4836-2015; OI Cauley, Jane/0000-0003-0752-4408; Rosano, Caterina/0000-0002-0909-1506; Rosano, Caterina/0000-0002-4271-6010; Boudreau, Robert/0000-0003-0162-5187; Carnahan, Ryan/0000-0002-7478-4739 FU National Institute on Aging [N01-AG-6-2101, N01-AG-6-2103, N01-AG-6-2106, R01-AG028050]; R01-AG028050 [R01-NR012459]; Intramural Research Program on the National Institutes of Health, National Institute on Aging; National Institutes of Health Training Grant [2T32AG000181] FX This work was supported by National Institute on Aging Contracts N01-AG-6-2101; N01-AG-6-2103; N01-AG-6-2106; National Institute on Aging grant R01-AG028050 and National Institute of Nursing Research grant R01-NR012459. This research was supported in part by the Intramural Research Program on the National Institutes of Health, National Institute on Aging. Andrea Metti is supported by a National Institutes of Health Training Grant 2T32AG000181. Andrea Metti would like to acknowledge Dr Mary Ganguli and Dr Oscar Lopez who both provided invaluable feedback and advice on this manuscript over multiple phases of its developments. NR 33 TC 5 Z9 5 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0197-4580 EI 1558-1497 J9 NEUROBIOL AGING JI Neurobiol. Aging PD DEC PY 2014 VL 35 IS 12 BP 2785 EP 2790 DI 10.1016/j.neurobiolaging.2014.05.030 PG 6 WC Geriatrics & Gerontology; Neurosciences SC Geriatrics & Gerontology; Neurosciences & Neurology GA AX9PB UT WOS:000347233200013 PM 24997674 ER PT J AU Borghero, G Pugliatti, M Marrosu, F Marrosu, MG Murru, MR Floris, G Cannas, A Parish, LD Occhineri, P Cau, TB Loi, D Ticca, A Traccis, S Manera, U Canosa, A Moglia, C Calvo, A Barberis, M Brunetti, M Pliner, HA Renton, AE Nalls, MA Traynor, BJ Restagno, G Chio, A AF Borghero, Giuseppe Pugliatti, Maura Marrosu, Francesco Marrosu, Maria Giovanna Murru, Maria Rita Floris, Gianluca Cannas, Antonino Parish, Leslie D. Occhineri, Patrizia Cau, Tea B. Loi, Daniela Ticca, Anna Traccis, Sebastiano Manera, Umberto Canosa, Antonio Moglia, Cristina Calvo, Andrea Barberis, Marco Brunetti, Maura Pliner, Hannah A. Renton, Alan E. Nalls, Mike A. Traynor, Bryan J. Restagno, Gabriella Chio, Adriano CA ITALSGEN & SARDINALS Consortia TI Genetic architecture of ALS in Sardinia SO NEUROBIOLOGY OF AGING LA English DT Article DE Amyotrophic lateral sclerosis; Sardinia; Phenotype; Genetics; Penetrance; Prognosis ID AMYOTROPHIC-LATERAL-SCLEROSIS; HEXANUCLEOTIDE REPEAT EXPANSION; TARDBP GENE; C9ORF72; MUTATIONS; FTD AB Conserved populations, such as Sardinians, displaying elevated rates of familial or sporadic amyotrophic lateral sclerosis (ALS) provide unique information on the genetics of the disease. Our aim was to describe the genetic profile of a consecutive series of ALS patients of Sardinian ancestry. All ALS patients of Sardinian ancestry, identified between 2008 and 2013 through the Italian ALS Genetic Consortium, were eligible to be included in the study. Patients and controls underwent the analysis of TARDBP, C9ORF72, SOD1, and FUS genes. Genetic mutations were identified in 155 out of 375 Sardinian ALS cases (41.3%), more commonly the p.A382T and p.G295S mutations of TARDBP and the GGGGCC hexanucleotide repeat expansion of C9ORF72. One patient had both p.G295S and p.A382T mutations of TARDBP and 8 carried both the heterozygous p.A382T mutation of TARDBP and a repeat expansion of C9ORF72. Patients carrying the p.A382T and the p.G295S mutations of TARDBP and the C9ORF72 repeat expansion shared distinct haplotypes across these loci. Patients with cooccurrence of C9ORF72 and TARDBP p.A382T missense mutation had a significantly lower age at onset and shorter survival. More than 40% of all cases on the island of Sardinia carry a mutation of an ALS-related gene, representing the highest percentage of ALS cases genetically explained outside of Scandinavia. Clinical phenotypes associated with different genetic mutations show some distinctive characteristics, but the heterogeneity between and among families carrying the same mutations implies that ALS manifestation is influenced by other genetic and nongenetic factors. (C) 2014 Elsevier Inc. All rights reserved. C1 [Borghero, Giuseppe; Marrosu, Francesco; Floris, Gianluca; Cannas, Antonino] Azienda Univ Osped Cagliari, Dept Neurol, Cagliari, Italy. [Borghero, Giuseppe; Marrosu, Francesco; Floris, Gianluca; Cannas, Antonino] Univ Cagliari, Cagliari, Italy. [Pugliatti, Maura; Parish, Leslie D.; Occhineri, Patrizia] Univ Sassari, Dept Clin & Expt Med, I-07100 Sassari, Italy. [Marrosu, Maria Giovanna; Murru, Maria Rita] Univ Cagliari, Multiple Sclerosis Ctr Lab, Cagliari, Italy. [Loi, Daniela] Azienda Sanit Locale 2, Olbia Tempio, Italy. [Ticca, Anna] Azienda Osped San Francesco, Dept Neurol, Nuoro, Italy. [Traccis, Sebastiano] Osped Antonio Segni, Dept Neurol, Ozieri, Italy. [Manera, Umberto; Canosa, Antonio; Moglia, Cristina; Calvo, Andrea; Barberis, Marco; Brunetti, Maura; Chio, Adriano] Univ Turin, Amyotroph Lateral Sclerosis Ctr, Rita Levi Montalcini Dept Neurosci, Turin, Italy. [Canosa, Antonio; Chio, Adriano] Univ Genoa, Dept Neurosci Ophthalmol Genet Rehabil & Child Hl, Genoa, Italy. [Canosa, Antonio; Calvo, Andrea; Chio, Adriano] Azienda Osped Univ Citta Salute & Sci, Turin, Italy. [Barberis, Marco; Brunetti, Maura; Restagno, Gabriella] Azienda Osped Univ Citta Salute & Sci, Mol Genet Lab, Turin, Italy. [Pliner, Hannah A.; Renton, Alan E.; Traynor, Bryan J.] NIA, Neuromuscular Dis Res Sect, Neurogenet Lab, Bethesda, MD 20892 USA. [Nalls, Mike A.] NIA, Mol Genet Sect, Neurogenet Lab, Bethesda, MD 20892 USA. [Traynor, Bryan J.] Johns Hopkins Univ, Dept Neurol, Brain Sci Inst, Baltimore, MD 21218 USA. [Chio, Adriano] NIT, Turin, Italy. RP Chio, A (reprint author), ALS Ctr, Rita Levi Montalcini Dept Neurosci, Via Cherasco 15, I-10126 Turin, Italy. EM achio@usa.net RI Pliner, Hannah/F-3608-2015; Calvo, Andrea/K-4141-2016; MANDRIOLI, JESSICA/K-7235-2016; Moglia, Cristina/K-4142-2016; OI Pliner, Hannah/0000-0003-1484-6501; Calvo, Andrea/0000-0002-5122-7243; MANDRIOLI, JESSICA/0000-0002-9244-9782; Moglia, Cristina/0000-0001-7377-7222; Chio, Adriano/0000-0001-9579-5341; Marrosu, Maria Giovanna/0000-0003-2334-2081 FU Italian Ministry of Health (Ministero della Salute, Ricerca Sanitaria Finalizzata) [RF-2010-2309849]; European Community [259867]; Joint Programme-Neurodegenerative Disease Research; Italian Ministry of Health; Strength Project - Italian Ministry of University and Research; Agenzia Italiana per la Ricerca sulla SLA (ARISLA) (SARDINIALS Project); Fondazione Vialli e Mauro per la SLA onlus; Fondazione Mauro e Anna Magnetto; Associazione Piemontese per l'Assistenza alla SLA; Assessorato alla Sanita, dell'Igiene e dell'Assistenza; Regione Autonoma della Sardegna; US National Institutes of Health, National Institute on Aging [Z01-AG000949-02]; National Institute of Neurological Disorder and Stroke; Center for Disease Control and Prevention/Agency for Toxic Substances and Disease Registry FX We thank the patients and research subjects who contributed samples for this study. This work was in part supported by the Italian Ministry of Health (Ministero della Salute, Ricerca Sanitaria Finalizzata, 2010, grant RF-2010-2309849), the European Community's Health Seventh Framework Programme (FP7/2007-2013 under grant agreement no. 259867), and the Joint Programme-Neurodegenerative Disease Research (Sophia Project, supported by the Italian Ministry of Health, and Strength Project, supported by the Italian Ministry of University and Research), Agenzia Italiana per la Ricerca sulla SLA (ARISLA) (SARDINIALS Project), Fondazione Vialli e Mauro per la SLA onlus, Fondazione Mauro e Anna Magnetto, Associazione Piemontese per l'Assistenza alla SLA, Assessorato alla Sanita, dell'Igiene e dell'Assistenza, and Regione Autonoma della Sardegna. This work was supported in part by the Intramural Research Programs of the US National Institutes of Health, National Institute on Aging (Z01-AG000949-02), and National Institute of Neurological Disorder and Stroke. The work was also supported by the Center for Disease Control and Prevention/Agency for Toxic Substances and Disease Registry. Author contributions-study concept and design: GB, MP, BJT, GR, and AC; acquisition of data: MRM, GF, AC, LDP, PO, TBC, DL, AT, UM, AC, CM, AC, MBa, MBr, HAP, AER, and MAN; analysis and interpretation of data: GB, MP, FM, MGM, MRM, AER, MAN, BJT, GR, and AC; drafting of the article: GB, MP, BJT, and AC; critical revision of the article for important intellectual content: GB, MP, FM, MGM, MRM, GF, AC, LDP, PC, TBC, DL, AT, UM, AC, CM, AC, MBa, MBr, HAP, AER, MAN, BJT, GR, and AC; obtained funding: GB, MP, GR, and AC; administrative, technical, and material support: MRM, GF, AC, LDP, PC, TBC, DL, AT, UM, AC, CM, AC, MBa, MBr, HAP, AER, and MAN; study supervision: GB, MP, BJT, GR, and AC. AC has full access to data. The corresponding author confirms that all these authors have read and approved the final draft of the article and given written permission to include their names in it. NR 25 TC 6 Z9 6 U1 0 U2 3 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0197-4580 EI 1558-1497 J9 NEUROBIOL AGING JI Neurobiol. Aging PD DEC PY 2014 VL 35 IS 12 AR 2882.e7 DI 10.1016/j.neurobiolaging.2014.07.012 PG 6 WC Geriatrics & Gerontology; Neurosciences SC Geriatrics & Gerontology; Neurosciences & Neurology GA AX9PB UT WOS:000347233200027 PM 25123918 ER PT J AU Sassi, C Guerreiro, R Gibbs, R Ding, JH Lupton, MK Troakes, C Al-Sarraj, S Niblock, M Gallo, JM Adnan, J Killick, R Brown, KS Medway, C Lord, J Turton, J Bras, J Morgan, K Powell, JF Singleton, A Hardy, J AF Sassi, Celeste Guerreiro, Rita Gibbs, Raphael Ding, Jinhui Lupton, Michelle K. Troakes, Claire Al-Sarraj, Safa Niblock, Michael Gallo, Jean-Marc Adnan, Jihad Killick, Richard Brown, Kristelle S. Medway, Christopher Lord, Jenny Turton, James Bras, Jose Morgan, Kevin Powell, John F. Singleton, Andrew Hardy, John CA Alzheimer's Res Uk Consortium TI Investigating the role of rare coding variability in Mendelian dementia genes (APP, PSEN1, PSEN2, GRN, MAPT, and PRNP) in late-onset Alzheimer's disease SO NEUROBIOLOGY OF AGING LA English DT Article DE Alzheimer's disease; Neurodegenerative dementia; APP; PSEN1; PSEN2; MAPT; GRN; PRNP; Exome sequencing ID GENOME-WIDE ASSOCIATION; PRION PROTEIN GENE; IDENTIFIES VARIANTS; COMMON VARIANTS; SEQUENCING DATA; MUTATIONS; DELETIONS; CD2AP; EPHA1; RISK AB The overlapping clinical and neuropathologic features between late-onset apparently sporadic Alzheimer's disease (LOAD), familial Alzheimer's disease (FAD), and other neurodegenerative dementias (frontotemporal dementia, corticobasal degeneration, progressive supranuclear palsy, and Creutzfeldt-Jakob disease) raise the question of whether shared genetic risk factors may explain the similar phenotype among these disparate disorders. To investigate this intriguing hypothesis, we analyzed rare coding variability in 6 Mendelian dementia genes (APP, PSEN1, PSEN2, GRN, MAPT, and PRNP), in 141 LOAD patients and 179 elderly controls, neuropathologically proven, from the UK. In our cohort, 14 LOAD cases (10%) and 11 controls (6%) carry at least 1 rare variant in the genes studied. We report a novel variant in PSEN1 (p.I168T) and a rare variant in PSEN2 (p.A237V), absent in controls and both likely pathogenic. Our findings support previous studies, suggesting that (1) rare coding variability in PSEN1 and PSEN2 may influence the susceptibility for LOAD and (2) GRN, MAPT, and PRNP are not major contributors to LOAD. Thus, genetic screening is pivotal for the clinical differential diagnosis of these neurodegenerative dementias. (C) 2014 Elsevier Inc. All rights reserved. C1 [Sassi, Celeste; Guerreiro, Rita; Gibbs, Raphael; Bras, Jose; Hardy, John] UCL, UCL Inst Neurol, Dept Mol Neurosci, London, England. [Sassi, Celeste; Guerreiro, Rita; Gibbs, Raphael; Ding, Jinhui; Singleton, Andrew] NIA, Neurogenet Lab, Bethesda, MD 20892 USA. [Lupton, Michelle K.; Troakes, Claire; Al-Sarraj, Safa; Niblock, Michael; Gallo, Jean-Marc; Adnan, Jihad; Killick, Richard; Powell, John F.] Kings Coll London, Inst Psychiat, London, England. [Brown, Kristelle S.; Medway, Christopher; Lord, Jenny; Turton, James; Morgan, Kevin] Univ Nottingham, Queens Med Ctr, Sch Life Sci, Nottingham NG7 2RD, England. RP Sassi, C (reprint author), NIH, Neurogenet Lab, 35 Convent Dr, Bethesda, MD 20892 USA. EM celeste.sassi.10@ucl.ac.uk RI Powell, John/G-4412-2011; Hardy, John/C-2451-2009; Singleton, Andrew/C-3010-2009; Troakes, Claire/K-4346-2015; Guerreiro, Rita/A-1327-2011; OI Powell, John/0000-0001-6124-439X; Bras, Jose/0000-0001-8186-0333; Killick, Richard/0000-0002-8815-3436 FU Alzheimer's Research UK; Medical Research Council (MRC); Wellcome Trust/MRC Joint Call in Neurodegeneration Award [WT089698]; National Institute for Health Research Biomedical Research Unit in Dementia at University College London Hospitals, University College London; National Institute on Aging [ZO1 AG000950-10]; National Institute of Neurological Disease and Stroke, National Institutes of Health (Department of Health and Human Services) [ZO1 AG000950-10]; Alzheimer's Association; [P50 AG016574]; [U01 AG006786]; [R01 AG18023] FX This study was supported by the Alzheimer's Research UK, the Medical Research Council (MRC), and the Wellcome Trust/MRC Joint Call in Neurodegeneration Award (WT089698) to the UK Parkinson's Disease Consortium (whose members are from the University College London, the National Institute for Health Research Biomedical Research Centre for Mental Health and Biomedical Research Unit for Dementia at the South London, and Maudsley NHS Foundation Trust and Kings College London; Institute of Neurology, the University of Sheffield, and the MRC Protein Phosphorylation Unit at the University of Dundee), grants (P50 AG016574, U01 AG006786, and R01 AG18023), the National Institute for Health Research Biomedical Research Unit in Dementia at University College London Hospitals, University College London; an anonymous donor, the Big Lottery (to Dr Morgan); a fellowship from Alzheimer's Research UK (to Dr Guerreiro); and the Intramural Research Programs of the National Institute on Aging and the National Institute of Neurological Disease and Stroke, National Institutes of Health (Department of Health and Human Services Project number, ZO1 AG000950-10). The MRC London Neurodegenerative Diseases Brain Bank and the Manchester Brain Bank from Brains for Dementia Research are jointly funded from Alzheimer's Research UK and Alzheimer's Association. The views expressed are those of the authors and not necessarily those of the NHS, the NIHR, or the Department of Health. NR 33 TC 4 Z9 5 U1 2 U2 7 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0197-4580 EI 1558-1497 J9 NEUROBIOL AGING JI Neurobiol. Aging PD DEC PY 2014 VL 35 IS 12 AR 2881.e1 DI 10.1016/j.neurobiolaging.2014.06.002 PG 6 WC Geriatrics & Gerontology; Neurosciences SC Geriatrics & Gerontology; Neurosciences & Neurology GA AX9PB UT WOS:000347233200023 PM 25104557 ER PT J AU Nie, LM Huang, P Li, WT Yan, XF Jin, A Wang, Z Tang, YX Wang, SJ Zhang, XF Niu, G Chen, XY AF Nie, Liming Huang, Peng Li, Weitao Yan, Xuefeng Jin, Albert Wang, Zhe Tang, Yuxia Wang, Shouju Zhang, Xiaofen Niu, Gang Chen, Xiaoyuan TI Early-Stage Imaging of Nanocarrier-Enhanced Chemotherapy Response in Living Subjects by Scalable Photoacoustic Microscopy SO ACS NANO LA English DT Article DE early prediction; chemotherapy response; nanocarrier; photoacoustic microscopy; scalable imaging; graphene oxide; signal amplification ID GRAPHENE OXIDE; GOLD NANOPARTICLES; PHOTOTHERMAL THERAPY; MOLECULAR TOMOGRAPHY; CONTRAST AGENTS; DRUG-DELIVERY; BREAST-CANCER; IN-VITRO; FUNCTIONALIZATION; GENERATION AB Conventional evaluation methods of chemotherapeutic efficacy such as tissue biopsy and anatomical measurement are either invasive with potential complications or dilatory to capture the rapid pathological changes. Here, a sensitive and resolution-scalable photoacoustic microscopy (PAM) with theranostic nanoformulation was developed to noninvasively monitor the therapy response in a timely manner. Ultrasmall graphene oxide nanosheets were designed as both drug-loading vehicle and photoacoustic signal amplifier to the tumor. With the signal enhancement by the injected contrast agents, the subtle microvascular changes of the chemotherapy response in tumor were advantagely revealed by our PAM system, which was much earlier than the morphological measurement by standard imaging techniques. High tumor uptake of the enhanced nanodrug with Cy5.5 labeling was validated by fluorescence imaging. At different observation scales, PAM offered unprecedented sensitivity of optical absorption and high spatial resolution over optical imaging. Our studies demonstrate the PAM system with synergistic theranostic strategy to be a multiplexing platform for tumor diagnosis, drug delivery, and chemotherapy response monitoring at a very early stage and in an effective way. C1 [Nie, Liming; Zhang, Xiaofen] Xiamen Univ, Sch Publ Hlth, State Key Lab Mol Vaccinol & Mol Diagnost, Xiamen 361102, Peoples R China. [Nie, Liming; Zhang, Xiaofen] Xiamen Univ, Sch Publ Hlth, Ctr Mol Imaging & Translat Med, Xiamen 361102, Peoples R China. [Huang, Peng; Li, Weitao; Yan, Xuefeng; Wang, Zhe; Tang, Yuxia; Wang, Shouju; Niu, Gang; Chen, Xiaoyuan] NIBIB, Lab Mol Imaging & Nanomed LOMIN, NIH, Bethesda, MD 20892 USA. [Li, Weitao] Nanjing Univ Aeronaut & Astronaut, Coll Automat Engn, Dept Biomed Engn, Nanjing 210016, Jiangsu, Peoples R China. [Jin, Albert] NIBIB, Lab Cellular Imaging & Macromol Biophys, NIH, Bethesda, MD 20982 USA. RP Nie, LM (reprint author), Xiamen Univ, Sch Publ Hlth, State Key Lab Mol Vaccinol & Mol Diagnost, Xiamen 361102, Peoples R China. EM nielm@xmu.edu.cn RI Huang, Peng/H-9985-2013; Nie, Liming/F-7718-2016; Huang, Peng/R-2480-2016; OI Huang, Peng/0000-0003-3651-7813; Jin, Albert/0000-0003-3826-1081 FU National Science Foundation of China [81301257, 81371596, 51373144]; National Basic Research Program of China (973 Program) [2013CB733802, 2014CB744503]; Intramural Research Program (IRP) of the National Institute of Biomedical Imaging and Bioengineering (NIBIB), National Institutes of Health (NIH) FX This work was supported by the National Science Foundation of China (81301257, 81371596, 51373144), the National Basic Research Program of China (973 Program 2013CB733802, 2014CB744503), and the Intramural Research Program (IRP) of the National Institute of Biomedical Imaging and Bioengineering (NIBIB), National Institutes of Health (NIH). The authors also acknowledge instrumental and technical support from nanoPAM Inc. NR 45 TC 21 Z9 23 U1 2 U2 48 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 1936-0851 EI 1936-086X J9 ACS NANO JI ACS Nano PD DEC PY 2014 VL 8 IS 12 BP 12141 EP 12150 DI 10.1021/nn505989e PG 10 WC Chemistry, Multidisciplinary; Chemistry, Physical; Nanoscience & Nanotechnology; Materials Science, Multidisciplinary SC Chemistry; Science & Technology - Other Topics; Materials Science GA AX8CL UT WOS:000347138000027 PM 25406986 ER PT J AU Wang, Z Zhang, RL Wang, ZL Wang, HF Wang, Y Zhao, J Wang, F Li, WT Niu, G Kiesewetter, DO Chen, XY AF Wang, Zhe Zhang, Ruili Wang, Zhongliang Wang, He-Fang Wang, Yu Zhao, Jun Wang, Fu Li, Weitao Niu, Gang Kiesewetter, Dale O. Chen, Xiaoyuan TI Bioinspired Nanocomplex for Spatiotemporal Imaging of Sequential mRNA Expression in Differentiating Neural Stem Cells SO ACS NANO LA English DT Article DE mRNA; imaging; gold nanoparticle; drug delivery; neural stem cell ID LIVING CELLS; MOLECULAR BEACON; MAMMALIAN-CELLS; MICELLE FLARES; RETINOIC ACID; CANCER-CELLS; NANOPROBE; NANOPARTICLES; LOCALIZATION; MONOLAYERS AB Messenger RNA plays a pivotal role in regulating cellular activities. The expression dynamics of specific mRNA contains substantial information on the intracellular milieu. Unlike the imaging of stationary mRNAs, real-time intracellular imaging of the dynamics of mRNA expression is of great value for investigating mRNA biology and exploring specific cellular cascades. In addition to advanced imaging methods, timely extracellular stimulation is another key factor in regulating the mRNA expression repertoire. The integration of effective stimulation and imaging into a single robust system would significantly improve stimulation efficiency and imaging accuracy, producing fewer unwanted artifacts. In this study, we developed a multifunctional nanocomplex to enable self-activating and spatiotemporal imaging of the dynamics of mRNA sequential expression during the neural stem cell differentiation process. This nanocomplex showed improved enzymatic stability, fast recognition kinetics, and high specificity. With a mechanism regulated by endogenous cell machinery, this nanocomplex realized the successive stimulating motif release and the dynamic imaging of chronological mRNA expression during neural stem cell differentiation without the use of transgenetic manipulation. The dynamic imaging montage of mRNA expression ultimately facilitated genetic heterogeneity analysis. In vivo lateral ventricle injection of this nanocomplex enabled endogenous neural stem cell activation and labeling at their specific differentiation stages. This nanocomplex is highly amenable as an alternative tool to explore the dynamics of intricate mRNA activities in various physiological and pathological conditions. C1 [Wang, Zhe; Zhang, Ruili; Wang, Zhongliang; Wang, He-Fang; Wang, Yu; Wang, Fu; Li, Weitao; Niu, Gang; Kiesewetter, Dale O.; Chen, Xiaoyuan] Natl Inst Biomed Imaging & Bioengn, Lab Mol Imaging & Nanomed, NIH, Bethesda, MD 20892 USA. [Zhang, Ruili; Wang, Zhongliang; Wang, Fu] Xidian Univ, Sch Life Sci & Technol, Xian 710071, Shaanxi, Peoples R China. [Zhao, Jun] NIMH, Unit Synapse Dev & Plast, NIH, Bethesda, MD 20892 USA. RP Wang, ZL (reprint author), Natl Inst Biomed Imaging & Bioengn, Lab Mol Imaging & Nanomed, NIH, Bethesda, MD 20892 USA. EM zhongliang.wang@nih.gov; shawn.chen@nih.gov RI Wang, He-Fang/D-7842-2011; OI Wang, He-Fang/0000-0003-4127-5038; Wang, Fu/0000-0001-9222-0833 FU Center for Neuroscience and Regenerative Medicine (CNRM) program at Henry M. Jackson Foundation; Intramural Research Program (IRP) of the National Institute of Biomedical Imaging and Bioengineering (NIBIB) at the National Institutes of Health (NIH) FX This study was supported, in part, by the Center for Neuroscience and Regenerative Medicine (CNRM) program at Henry M. Jackson Foundation and the Intramural Research Program (IRP) of the National Institute of Biomedical Imaging and Bioengineering (NIBIB) at the National Institutes of Health (NIH). NR 44 TC 5 Z9 5 U1 6 U2 66 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 1936-0851 EI 1936-086X J9 ACS NANO JI ACS Nano PD DEC PY 2014 VL 8 IS 12 BP 12386 EP 12396 DI 10.1021/nn505047n PG 11 WC Chemistry, Multidisciplinary; Chemistry, Physical; Nanoscience & Nanotechnology; Materials Science, Multidisciplinary SC Chemistry; Science & Technology - Other Topics; Materials Science GA AX8CL UT WOS:000347138000051 PM 25494492 ER PT J AU Spielberg, F Levy, V Lensing, S Chattopadhyay, I Venkatasubramanian, L Acevedo, N Wolff, P Callabresi, D Philip, S Lopez, TP Padian, N Blake, DR Gaydos, CA AF Spielberg, Freya Levy, Vivian Lensing, Shelly Chattopadhyay, Ishita Venkatasubramanian, Lalitha Acevedo, Nincoshka Wolff, Peter Callabresi, Debra Philip, Susan Lopez, Teresa P. Padian, Nancy Blake, Diane R. Gaydos, Charlotte A. TI Fully Integrated e-Services for Prevention, Diagnosis, and Treatment of Sexually Transmitted Infections: Results of a 4-County Study in California SO AMERICAN JOURNAL OF PUBLIC HEALTH LA English DT Article ID CHLAMYDIA-TRACHOMATIS; VAGINAL SWABS; NEISSERIA-GONORRHOEAE; HOME; INTERNET; ACCEPTABILITY; METAANALYSIS; URINE; COST AB Objectives. We examined the acceptability, feasibility, and cost of a fully integrated online system (eSTI) for sexually transmitted infection (STI) testing, treatment, and linkage to care with 4 Northern California health departments. Methods. In April 2012, we implemented the eSTI system, which provided education; testing of self-collected vaginal swabs for chlamydia, gonorrhea, and trichomoniasis; e-prescriptions; e-partner notification; and data integration with clinic electronic health records. We analyzed feasibility, acceptability, and cost measures. Results. During a 3-month period, 217 women aged 18 to 30 years enrolled; 67% returned the kit. Of these, 92% viewed their results online. STI prevalence was 5.6% (chlamydia and trichomoniasis). All participants with STIs received treatment either the same day at a pharmacy (62%) or within 7 days at a clinic (38%). Among participants completing follow-up surveys, 99% would recommend the online eSTI system to a friend, and 95% preferred it over clinic-based testing within a study. Conclusions. The fully integrated eSTI system has the potential to increase diagnosis and treatment of STIs with higher patient satisfaction at a potentially lower cost. C1 [Spielberg, Freya] George Washington Univ, Dept Prevent & Community Hlth, Washington, DC 20052 USA. [Levy, Vivian; Lopez, Teresa P.] San Mateo Cty Hlth Syst, San Mateo, CA USA. [Lensing, Shelly] Univ Arkansas Med Sci, Dept Biostat, Little Rock, AR 72205 USA. [Chattopadhyay, Ishita] Res Triangle Inst Int, Res Triangle Pk, NC USA. [Venkatasubramanian, Lalitha; Acevedo, Nincoshka] FHI 360, Durham, NC USA. [Wolff, Peter] NIAID, Bethesda, MD 20892 USA. [Callabresi, Debra] N Ton, Los Angeles, CA USA. [Philip, Susan] San Francisco Dept Publ Hlth, San Francisco, CA USA. [Padian, Nancy] Berkeley Sch Publ Hlth, Berkeley, CA USA. [Blake, Diane R.] Univ Massachusetts, Sch Med, Dept Pediat, Worcester, MA USA. [Gaydos, Charlotte A.] Johns Hopkins Univ, Dept Med, Div Infect Dis, Baltimore, MD USA. RP Spielberg, F (reprint author), George Washington Univ, Dept Prevent & Community Hlth, 2175 K St NW,Suite 700,Room 728, Washington, DC 20052 USA. EM fspielberg@e-mail.gwu.edu FU National Institute of Allergy and Infectious Diseases through the Sexually Transmitted Infections Clinical Trials Group [HHSN266200400074C]; National Institute of Biomedical Imaging and Bioengineering, NIH [U54EB007958]; National Institute of Allergy and Infectious Diseases, NIH [U-01 AI068613] FX This work was supported by the National Institute of Allergy and Infectious Diseases (HHSN266200400074C) through the Sexually Transmitted Infections Clinical Trials Group. C.A. Gaydos was also supported by the National Institute of Biomedical Imaging and Bioengineering, NIH U54EB007958 and National Institute of Allergy and Infectious Diseases, NIH U-01 AI068613. NR 20 TC 6 Z9 6 U1 0 U2 3 PU AMER PUBLIC HEALTH ASSOC INC PI WASHINGTON PA 800 I STREET, NW, WASHINGTON, DC 20001-3710 USA SN 0090-0036 EI 1541-0048 J9 AM J PUBLIC HEALTH JI Am. J. Public Health PD DEC PY 2014 VL 104 IS 12 BP 2313 EP 2320 DI 10.2105/AJPH.2014.302302 PG 8 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA AX9GB UT WOS:000347210500038 PM 25320878 ER PT J AU Han, B Compton, WM Gfroerer, J McKeon, R AF Han, Beth Compton, Wilson M. Gfroerer, Joseph McKeon, Richard TI Mental Health Treatment Patterns Among Adults With Recent Suicide Attempts in the United States SO AMERICAN JOURNAL OF PUBLIC HEALTH LA English DT Article ID COMMON OUTCOMES; RELATIVE RISK; SUBSTANCE USE; CARE; BEHAVIORS; IDEATION; COHORT; MODEL; INDIVIDUALS; DISORDERS AB Objectives. We examined mental health treatment patterns among adults with suicide attempts in the past 12 months in the United States. Methods. We examined data from 2000 persons, aged 18 years or older, who participated in the 2008 to 2012 National Survey on Drug Use and Health and who reported attempting suicide in the past 12 months. We applied descriptive analyses and multivariable logistic regression models. Results. In adults who attempted suicide in the past year, 56.3% received mental health treatment, but half of those who received treatment perceived unmet treatment needs, and of the 43.0% who did not receive mental health treatment, one fourth perceived unmet treatment needs. From 2008 to 2012, the mental health treatment rate among suicide attempters remained unchanged. Factors associated with receipt of mental health treatment varied by perceived unmet treatment need and receipt of medical attention that resulted from a suicide attempt. Conclusions. Suicide prevention strategies that focus on suicide attempters are needed to increase their access to mental health treatments that meet their needs. To be effective, these strategies need to account for language and cultural differences and barriers to financial and treatment delivery. C1 [Han, Beth; Gfroerer, Joseph; McKeon, Richard] Subst Abuse & Mental Hlth Serv Adm, Rockville, MD USA. [Compton, Wilson M.] NIDA, NIH, Bethesda, MD 20892 USA. RP Han, B (reprint author), 1 Choke Cherry Rd,Room 2-1079, Rockville, MD 20857 USA. EM Beth.Han@SAMHSA.HHS.GOV NR 37 TC 7 Z9 7 U1 1 U2 7 PU AMER PUBLIC HEALTH ASSOC INC PI WASHINGTON PA 800 I STREET, NW, WASHINGTON, DC 20001-3710 USA SN 0090-0036 EI 1541-0048 J9 AM J PUBLIC HEALTH JI Am. J. Public Health PD DEC PY 2014 VL 104 IS 12 BP 2359 EP 2368 DI 10.2105/AJPH.2014.302163 PG 10 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA AX9GB UT WOS:000347210500044 PM 25322299 ER PT J AU Garrison, AR Giomarelli, BG Lear-Rooney, CM Saucedo, CJ Yellayi, S Krumpe, LRH Rose, M Paragas, J Bray, M Olinger, GG McMahon, JB Huggins, J O'Keefe, BR AF Garrison, Aura R. Giomarelli, Barbara G. Lear-Rooney, Calli M. Saucedo, Carrie J. Yellayi, Srikanth Krumpe, Lauren R. H. Rose, Maura Paragas, Jason Bray, Mike Olinger, Gene G., Jr. McMahon, James B. Huggins, John O'Keefe, Barry R. TI The cyanobacterial lectin scytovirin displays potent in vitro and in vivo activity against Zaire Ebola virus SO ANTIVIRAL RESEARCH LA English DT Article DE Ebola; Scytovirin; Lectin; Natural product; Cyanobacteria ID ANTI-HIV PROTEIN; CYANOVIRIN-N; INACTIVATING PROTEIN; FILOVIRUS INFECTION; SCYTONEMA-VARIUM; GLYCOPROTEIN; ENTRY; GRIFFITHSIN; INHIBITOR; BINDS AB The cyanobacterial lectin scytovirin (SVN) binds with high affinity to mannose-rich oligosaccharides on the envelope glycoprotein (GP) of a number of viruses, blocking entry into target cells. In this study, we assessed the ability of SVN to bind to the envelope GP of Zaire Ebola virus (ZEBOV) and inhibit its replication. SVN interacted specifically with the protein's mucin-rich domain. In cell culture, it inhibited ZEBOV replication with a 50% virus-inhibitory concentration (EC50) of 50 nM, and was also active against the Angola strain of the related Marburg virus (MARV), with a similar EC50. Injected subcutaneously in mice, SVN reached a peak plasma level of 100 nm in 45 min, but was cleared within 4 h. When ZEBOV-infected mice were given 30 mg/kg/day of SVN by subcutaneous injection every 6 h, beginning the day before virus challenge, 9 of 10 animals survived the infection, while all infected, untreated mice died. When treatment was begun one hour or one day after challenge, 70-90% of mice survived. Quantitation of infectious virus and viral RNA in samples of serum, liver and spleen collected on days 2 and 5 postinfection showed a trend toward lower titers in treated than control mice, with a significant decrease in liver titers on day 2. Our findings provide further evidence of the potential of natural lectins as therapeutic agents for viral infections. Published by Elsevier B.V. C1 [Garrison, Aura R.; Lear-Rooney, Calli M.; Paragas, Jason; Bray, Mike; Olinger, Gene G., Jr.; Huggins, John] US Army, Med Res Inst Infect Dis, Dept Viral Therapeut, Div Virol, Ft Detrick, MD 21702 USA. [Giomarelli, Barbara G.; Saucedo, Carrie J.; Krumpe, Lauren R. H.; Rose, Maura; McMahon, James B.; O'Keefe, Barry R.] NCI, Ctr Canc Res, Mol Targets Lab, NIH,Frederick Natl Lab Canc Res, Ft Detrick, MD 21702 USA. [Saucedo, Carrie J.; Krumpe, Lauren R. H.] Leidos Biomed Res Inc, Frederick Natl Lab Canc Res, Basic Sci Program, Frederick, MD 21702 USA. [Yellayi, Srikanth] NIAID, Off Chief Scientist, Integrated Res Facil, Div Clin Res, Frederick, MD USA. [Bray, Mike] NIAID, Div Clin Res, NIH, Bethesda, MD 20892 USA. RP O'Keefe, BR (reprint author), NCI, Mol Targets Lab, Bldg 562,Rm 201, Ft Detrick, MD 21702 USA. EM okeefeba@mail.nih.gov FU Intramural Research Program of the NIH, National Cancer Institute, Center for Cancer Research and the NIAID Trans-NIH/FDA Biodefense Grant Program; Frederick National Laboratory for Cancer Research, National Institutes of Health [HHSN261200800001E] FX This research was supported by the Intramural Research Program of the NIH, National Cancer Institute, Center for Cancer Research and the NIAID Trans-NIH/FDA Biodefense Grant Program. 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. 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. Opinions, interpretations, conclusions, and recommendations are those of the author and are not necessarily endorsed by the U.S. Army. NR 24 TC 11 Z9 13 U1 3 U2 26 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0166-3542 EI 1872-9096 J9 ANTIVIR RES JI Antiviral Res. PD DEC PY 2014 VL 112 BP 1 EP 7 DI 10.1016/j.antiviral.2014.09.012 PG 7 WC Pharmacology & Pharmacy; Virology SC Pharmacology & Pharmacy; Virology GA AX5CE UT WOS:000346943900001 PM 25265598 ER PT J AU Smith, DR Holbrook, MR Gowen, BB AF Smith, Darci R. Holbrook, Michael R. Gowen, Brian B. TI Animal models of viral hemorrhagic fever SO ANTIVIRAL RESEARCH LA English DT Review DE Animal models; Viral hemorrhagic fever; Rodents; Non-human primates; Medical countermeasures ID RIFT-VALLEY-FEVER; EXPERIMENTAL YELLOW-FEVER; EBOLA-VIRUS INFECTION; HANTAVIRUS PULMONARY SYNDROME; SYRIAN GOLDEN-HAMSTER; THROMBOCYTOPENIA SYNDROME VIRUS; EXPERIMENTAL LASSA FEVER; KYASANUR-FOREST-DISEASE; SIN-NOMBRE-VIRUS; LYMPHOCYTIC CHORIOMENINGITIS VIRUS AB The term "viral hemorrhagic fever" (VHF) designates a syndrome of acute febrile illness, increased vascular permeability and coagulation defects which often progresses to bleeding and shock and may be fatal in a significant percentage of cases. The causative agents are some 20 different RNA viruses in the families Arenaviridae, Bunyaviridae, Filoviridae and Flaviviridae, which are maintained in a variety of animal species and are transferred to humans through direct or indirect contact or by an arthropod vector. Except for dengue, which is transmitted among humans by mosquitoes, the geographic distribution of each type of VHF is determined by the range of its animal reservoir. Treatments are available for Argentine HF and Lassa fever, but no approved countermeasures have been developed against other types of VHF. The development of effective interventions is hindered by the sporadic nature of most infections and their occurrence in geographic regions with limited medical resources. Laboratory animal models that faithfully reproduce human disease are therefore essential for the evaluation of potential vaccines and therapeutics. The goal of this review is to highlight the current status of animal models that can be used to study the pathogenesis of VHF and test new countermeasures. (C) 2014 Elsevier B.V. All rights reserved. C1 [Smith, Darci R.] So Res Inst, Frederick, MD 21701 USA. [Holbrook, Michael R.] NIAID, Integrated Res Facil, NIH, Frederick, MD USA. [Gowen, Brian B.] Utah State Univ, Inst Antiviral Res, Logan, UT 84322 USA. [Gowen, Brian B.] Utah State Univ, Dept Anim Dairy & Vet Sci, Logan, UT 84322 USA. RP Smith, DR (reprint author), So Res Inst, 431 Aviat Way, Frederick, MD 21701 USA. EM smithdr@southernresearch.org FU NIAID [HHSN272200200016I] FX The authors would like to thank Jiro Wada for his illustration work. MRH is an employee of Battelle Memorial Institute under its prime contract with NIAID No. HHSN272200200016I. The information presented here is the responsibility of the authors and does not necessarily represent views or policies of the US Department of Health and Human Services or Battelle Memorial Institute. NR 336 TC 8 Z9 9 U1 2 U2 23 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0166-3542 EI 1872-9096 J9 ANTIVIR RES JI Antiviral Res. PD DEC PY 2014 VL 112 BP 59 EP 79 DI 10.1016/j.antiviral.2014.10.001 PG 21 WC Pharmacology & Pharmacy; Virology SC Pharmacology & Pharmacy; Virology GA AX5CE UT WOS:000346943900007 PM 25448088 ER PT J AU Kanevskiy, LM Erokhina, SA Streltsova, MA Telford, WG Sapozhnikov, AM Kovalenko, EI AF Kanevskiy, L. M. Erokhina, S. A. Streltsova, M. A. Telford, W. G. Sapozhnikov, A. M. Kovalenko, E. I. TI Bacterial Lipopolysaccharide Activates CD57-Negative Human NK Cells SO BIOCHEMISTRY-MOSCOW LA English DT Article DE NK cells; lipopolysaccharide; IFN-gamma production; CD57; cytotoxicity; TLR4 ID NATURAL-KILLER-CELLS; TOLL-LIKE RECEPTOR; IMMUNE-RESPONSE; IFN-GAMMA; RECOGNITION; MACROPHAGES; EXPRESSION; SEPSIS; SUBSET; MODEL AB NK cells play an important regulatory role in sepsis by induction and augmentation of proinflammatory reactions in early stages of the septic process and by suppression of immune response in later stages of inflammation. The present work was aimed at the effect of bacterial lipopolysaccharide (LPS), the main pathogenic factor of sepsis development, on human NK cells ex vivo. We show that LPS activates immature CD57-negative NK cells, which typically constitute less than half of the normal NK cell population in human peripheral blood. Under conditions of NK cell stimulation with IL-2, addition of LPS provokes an increase in IFN-gamma production. However, LPS both increased and inhibited NK cell cytotoxic activity. It is important to note that the activation of NK cells on LPS addition was observed in the absence of TLR4 on the NK cell surface. These results confirm our previous data arguing for a direct interaction of LPS with NK cells and evidence an atypical mechanism of LPS-induced NK cell activation without the involvement of surface TLR4. C1 [Kanevskiy, L. M.; Erokhina, S. A.; Streltsova, M. A.; Sapozhnikov, A. M.; Kovalenko, E. I.] Russian Acad Sci, Shemyakin & Ovchinnikov Inst Bioorgan Chem, Moscow 117997, Russia. [Erokhina, S. A.; Sapozhnikov, A. M.] Moscow MV Lomonosov State Univ, Fac Biol, Moscow 119991, Russia. [Telford, W. G.] NCI, Expt Transplantat & Immunol Branch, NIH, Bethesda, MD 20892 USA. RP Kovalenko, EI (reprint author), Russian Acad Sci, Shemyakin & Ovchinnikov Inst Bioorgan Chem, Ul Miklukho Maklaya 16-10, Moscow 117997, Russia. EM leonid_kanewski@mail.ru; lenkovalen@mail.ru RI Streltsova, Maria/S-2066-2016; Kovalenko, Elena/S-2086-2016 FU Russian Foundation for Basic Research [13-04-02041, 14-04-01842] FX This work was supported by the Russian Foundation for Basic Research grants (Nos. 13-04-02041 and 14-04-01842). NR 30 TC 1 Z9 1 U1 1 U2 6 PU MAIK NAUKA/INTERPERIODICA/SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013-1578 USA SN 0006-2979 EI 0320-9725 J9 BIOCHEMISTRY-MOSCOW+ JI Biochem.-Moscow PD DEC PY 2014 VL 79 IS 12 BP 1339 EP 1348 DI 10.1134/S0006297914120074 PG 10 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA AX4UE UT WOS:000346926000007 PM 25716727 ER PT J AU Sissung, TM Price, DK Del Re, M Ley, AM Giovannetti, E Figg, WD Danesi, R AF Sissung, Tristan M. Price, Douglas K. Del Re, Marzia Ley, Ariel M. Giovannetti, Elisa Figg, William D. Danesi, Romano TI Genetic variation: effect on prostate cancer SO BIOCHIMICA ET BIOPHYSICA ACTA-REVIEWS ON CANCER LA English DT Review DE Pharmacogenomics; Prostate cancer; Androgen deprivation therapy; Chemotherapy; Steroid ID ANDROGEN-DEPRIVATION THERAPY; ENDOTHELIAL GROWTH-FACTOR; SINGLE NUCLEOTIDE POLYMORPHISMS; 5-ALPHA-REDUCTASE TYPE-II; GENOME-WIDE ASSOCIATION; NORTH INDIAN POPULATION; VITAMIN-D-RECEPTOR; CAG REPEAT LENGTH; REDUCTASE TYPE-II; CYP17 GENE AB The crucial role of androgens in the development of prostate cancer is well established. The aim of this review is to examine the role of constitutional (germline) and tumor-specific (somatic) polymorphisms within important regulatory genes of prostate cancer. These include genes encoding enzymes of the androgen biosynthetic pathway, the androgen receptor gene, genes that encode proteins of the signal transduction pathways that may have a role in disease progression and survival, and genes involved in prostate cancer angiogenesis. Characterization of deregulated pathways critical to cancer cell growth have lead to the development of new treatments, including the CYP17 inhibitor abiraterone and clinical trials using novel drugs that are ongoing or recently completed [1]. The pharmacogenetics of the drugs used to treat prostate cancer will also be addressed. This review will define how germline polymorphisms are known affect a multitude of pathways, and therefore phenotypes, in prostate cancer etiology, progression, and treatment. Published by Elsevier B.V. C1 [Sissung, Tristan M.; Price, Douglas K.; Ley, Ariel M.; Figg, William D.] NCI, NIH, Bethesda, MD 20892 USA. [Del Re, Marzia; Giovannetti, Elisa; Danesi, Romano] Univ Pisa, Dept Clin & Expt Med, I-56100 Pisa, Italy. RP Figg, WD (reprint author), NCI, NIH, Bethesda, MD 20892 USA. RI Figg Sr, William/M-2411-2016; OI Del Re, Marzia/0000-0001-7343-6161 FU Intramural NIH HHS [ZIA BC010627-10] NR 213 TC 8 Z9 8 U1 2 U2 10 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0304-419X EI 0006-3002 J9 BBA-REV CANCER JI Biochim. Biophys. Acta-Rev. Cancer PD DEC PY 2014 VL 1846 IS 2 BP 446 EP 456 DI 10.1016/j.bbcan.2014.08.007 PG 11 WC Biochemistry & Molecular Biology; Biophysics; Oncology SC Biochemistry & Molecular Biology; Biophysics; Oncology GA AY0BQ UT WOS:000347263400014 PM 25199985 ER PT J AU Volkin, D Turkbey, B Hoang, AN Rais-Bahrami, S Yerram, N Walton-Diaz, A Nix, JW Wood, BJ Choyke, PL Pinto, PA AF Volkin, Dmitry Turkbey, Baris Hoang, Anthony N. Rais-Bahrami, Soroush Yerram, Nitin Walton-Diaz, Annerleim Nix, Jeffrey W. Wood, Bradford J. Choyke, Peter L. Pinto, Peter A. TI Multiparametric magnetic resonance imaging (MRI) and subsequent MRI/ultrasonography fusion-guided biopsy increase the detection of anteriorly located prostate cancers SO BJU INTERNATIONAL LA English DT Article DE prostatic adenocarcinoma; functional MRI; cancer screening; prostate biopsy ID CLINICAL-SIGNIFICANCE; TUMOR VOLUME AB ObjectiveTo describe the detection rate of anteriorly located prostate cancer (PCa) with the addition of magnetic resonance imaging (MRI)/ultrasonography (US) fusion-guided biopsy (FGB) to the standard transrectal ultrasonography (TRUS)-guided biopsy. Patients and MethodsAll patients, regardless of their biopsy history, who were referred for clinical suspicion of PCa (i.e elevated prostate-specific antigen (PSA) level and abnormal digital rectal examination) underwent 3T multiparametric-MRI (mpMRI) screening; and those with suspicious lesions in the anterior region of the prostate were identified. Patients then received a FGB of all suspicious lesions in addition to a systematic 12-core extended sextant TRUS-guided biopsy. We conducted a lesion-based analysis comparing cancer detection rates of anterior targets using FGB vs systematic cores taken from the same anatomic sextant within the prostate. Lengths of cancer in the most involved core were also compared between the two biopsy techniques used. Patients with only anterior targets were analysed separately. ResultsOf 499 patients undergoing FGB, 162 had a total of 241 anterior lesions. The mean age, PSA level and prostate volume in this group were 62 years, 12.7ng/dL, and 57mL, respectively. In total, PCa was diagnosed in 121 anterior lesions (50.2%) identified on mpMRI. Sixty-two (25.7%) of these anterior lesions were documented as positive for cancer on systematic 12-core TRUS-guided biopsy cores, while 97 (40.2%) were positive on the targeted FGB cores (P = 0.001). In lesions that were positive on both FGB and TRUS biopsy, the most involved core was 112% longer on FGB (3.7 vs 1.6mm, P 0.01). Forty-two patients had only anterior lesions on mpMRI; of these, 24 (57.1%) were found to have cancer on the FGB + TRUS biopsy platform. Six patients were positive on FGB only and 13 were positive on both biopsy techniques; however, 7/13 patients were upgraded to a higher Gleason score after FGB. All five patients positive on TRUS biopsy only were candidates for active surveillance. ConclusionThe results showed that FGB detects significantly more anteriorly located PCa than does TRUS-guided biopsy alone and it may serve as an effective tool for the subset of patients with such tumours. C1 [Volkin, Dmitry; Hoang, Anthony N.; Rais-Bahrami, Soroush; Yerram, Nitin; Walton-Diaz, Annerleim; Nix, Jeffrey W.; Pinto, Peter A.] NCI, Urol Oncol Branch, NIH, Bethesda, MD 20892 USA. [Turkbey, Baris; Choyke, Peter L.] NCI, Mol Imaging Program, NIH, Bethesda, MD 20892 USA. [Wood, Bradford J.; Pinto, Peter A.] NCI, Ctr Intervent Oncol, NIH, Bethesda, MD 20892 USA. RP Pinto, PA (reprint author), NCI, Urol Oncol Branch, NIH, 10 Ctr Dr,MSC1210,Building10,CRCRoom2W-5940, Bethesda, MD 20892 USA. EM pintop@mail.nih.gov OI Rais-Bahrami, Soroush/0000-0001-9466-9925 NR 33 TC 24 Z9 24 U1 0 U2 2 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1464-4096 EI 1464-410X J9 BJU INT JI BJU Int. PD DEC PY 2014 VL 114 IS 6B BP E43 EP E49 DI 10.1111/bju.12670 PG 7 WC Urology & Nephrology SC Urology & Nephrology GA AX5ST UT WOS:000346988300006 PM 24712649 ER PT J AU Mitchell, SA Hoffman, AJ Clark, JC DeGennaro, RM Poirier, P Robinson, CB Weisbrod, BL AF Mitchell, Sandra A. Hoffman, Amy J. Clark, Jane C. DeGennaro, Regina M. Poirier, Patricia Robinson, Carolene B. Weisbrod, Breanna L. TI Putting Evidence Into Practice: An Update of Evidence-Based Interventions for Cancer-Related Fatigue During and Following Treatment SO CLINICAL JOURNAL OF ONCOLOGY NURSING LA English DT Article DE cancer-related fatigue; cancer; management; nursing; evidence-based practice ID QUALITY-OF-LIFE; RANDOMIZED CONTROLLED-TRIAL; PATIENTS RECEIVING CHEMOTHERAPY; PLACEBO-CONTROLLED TRIAL; ERYTHROPOIESIS-STIMULATING AGENTS; COGNITIVE-BEHAVIOR THERAPY; L-CARNITINE SUPPLEMENTATION; STEM-CELL TRANSPLANTATION; STAGE BREAST-CANCER; III CLINICAL-TRIAL AB Cancer-related fatigue (CRF) has deleterious effects on physical, social, cognitive, and vocational functioning, and causes emotional and spiritual distress for patients and their families; however, it remains under-recognized and undertreated. This article critically reviews and integrates the available empirical evidence supporting the efficacy of pharmacologic and nonpharmacologic treatment approaches to CRF, highlighting new evidence since 2007 and 2009 Putting Evidence Into Practice publications. Interventions that are recommended for practice or likely to be effective in improving fatigue outcomes include exercise; screening for treatable risk factors; management of concurrent symptoms; yoga; structured rehabilitation; Wisconsin ginseng; cognitive-behavioral therapies for insomnia, pain, and depression; mindfulness-based stress reduction; and psychoeducational interventions such as anticipatory guidance, psychosocial support, and energy conservation and activity management. This information can be applied to improve the management of CRF, inform health policy and program development, shape the design of clinical trials of new therapies for CRF, and drive basic and translational research. C1 [Mitchell, Sandra A.] Natl Canc Ctr, Div Canc Control & Populat Sci, Bethesda, MD 20892 USA. [Hoffman, Amy J.] Michigan State Univ, Coll Nursing, E Lansing, MI 48824 USA. [Clark, Jane C.] Georgia Ctr Oncol Res & Educ, Atlanta, GA USA. [DeGennaro, Regina M.] Univ Virginia, Sch Nursing, Charlottesville, VA 22903 USA. [Poirier, Patricia] Univ Maine, Sch Nursing, Orono, ME USA. [Robinson, Carolene B.] UnityPoint Hlth Trinity, Moline, IL USA. [Weisbrod, Breanna L.] Univ Kansas Hosp, Dept Nursing, Kansas City, KS USA. RP Mitchell, SA (reprint author), Natl Canc Ctr, Div Canc Control & Populat Sci, Bethesda, MD 20892 USA. EM mitchlls@mailnih.gov NR 324 TC 20 Z9 21 U1 9 U2 44 PU ONCOLOGY NURSING SOC PI PITTSBURGH PA 125 ENTERPRISE DR, PITTSBURGH, PA 15275 USA SN 1092-1095 EI 1538-067X J9 CLIN J ONCOL NURS JI Clin. J. Oncol. Nurs. PD DEC PY 2014 VL 18 SU S BP 38 EP 58 DI 10.1188/14.CJON.S3.38-58 PG 21 WC Oncology; Nursing SC Oncology; Nursing GA AX9OP UT WOS:000347232100005 PM 25427608 ER PT J AU Wester, JC McBain, CJ AF Wester, Jason C. McBain, Chris J. TI Behavioral state-dependent modulation of distinct interneuron subtypes and consequences for circuit function SO CURRENT OPINION IN NEUROBIOLOGY LA English DT Article ID CHOLECYSTOKININ-POSITIVE INTERNEURONS; CORTICAL INTERNEURONS; GABAERGIC NEURONS; VISUAL-CORTEX; BARREL CORTEX; CHOLINERGIC MODULATION; SOMATOSENSORY CORTEX; NICOTINIC RECEPTORS; PYRAMIDAL NEURONS; RAT HIPPOCAMPUS AB Multiple neuromodulators regulate neuronal response properties and synaptic connections in order to adjust circuit function. Inhibitory interneurons are a diverse group of cells that are differentially modulated depending on neuronal subtype and play key roles in regulating local circuit activity. Importantly, new tools to target specific subtypes are greatly improving our understanding of interneuron circuits and their modulation. Indeed, recent work has demonstrated that during different behavioral states interneuron activity changes in a subtype specific manner in both neocortex and hippocampus. Furthermore, in neocortex, modulation of specific interneuron microcircuits results in pyramidal cell disinhibition with important consequences for synaptic plasticity and animal behavior. Thus, neuromodulators tune the output of different interneuron subtypes to provide neural circuits with great flexibility. C1 [Wester, Jason C.; McBain, Chris J.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Program Dev Neurobiol, NIH, Bethesda, MD 20892 USA. RP McBain, CJ (reprint author), Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Program Dev Neurobiol, NIH, Bethesda, MD 20892 USA. EM mcbainc@mail.nih.gov FU National Institute of Child Health and Human Development [Z1A-HD001205-21] FX We thank the National Institute of Child Health and Human Development (Z1A-HD001205-21) for funding support. We also thank Ken Pelkey for helpful comments on this manuscript, as well as Carl Petersen, Bernardo Rudy, and Peyman Golshani for their kind permission to modify the figures presented here. NR 60 TC 11 Z9 11 U1 1 U2 12 PU CURRENT BIOLOGY LTD PI LONDON PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND SN 0959-4388 EI 1873-6882 J9 CURR OPIN NEUROBIOL JI Curr. Opin. Neurobiol. PD DEC PY 2014 VL 29 BP 118 EP 125 DI 10.1016/j.conb.2014.07.007 PG 8 WC Neurosciences SC Neurosciences & Neurology GA AX7YS UT WOS:000347128200017 PM 25058112 ER PT J AU Horvat, B Berges, BK Lusso, P AF Horvat, Branka Berges, Bradford K. Lusso, Paolo TI Recent developments in animal models for human herpesvirus 6A and 6B SO CURRENT OPINION IN VIROLOGY LA English DT Article ID IN-VITRO SUSCEPTIBILITY; MULTIPLE-SCLEROSIS; CELLULAR RECEPTOR; HIV-1 INFECTION; DOWN-REGULATION; T-LYMPHOCYTES; HUMAN-HERPESVIRUS-6; HHV-6; MICE; ANTIGEN AB Progress in the identification of suitable animal models for human herpesvirus (HHV)-6A and HHV-6B infections has been slow. Recently, new models have been established, mainly for HHV-6A, which reproduce some pathological features seen in humans. Neuroinflammatory signs were observed in infected marmosets and CD46-transgenic mice; although viral replication was not prominent, persistence of viral DNA and specific immunologic responses were detected, suggesting an immune-mediated pathogenic mechanism. Pig-tailed macaques showed robust viral replication concomitant with acute-phase symptoms, and provided a model to study the effects of HHV-6A on AIDS progression. In humanized mice, viral replication was less evident, but infection led to T-cell alterations. Altogether, these recent developments have opened new perspectives for studying the pathogenic role of HHV-6A in humans. C1 [Horvat, Branka] INSERM, U1111, F-69008 Lyon, France. [Horvat, Branka] CNRS, UMR5308, Lyon, France. [Horvat, Branka] Univ Lyon 1, F-69365 Lyon, France. [Horvat, Branka] Ecole Normale Super Lyon, F-69364 Lyon, France. [Berges, Bradford K.] Brigham Young Univ, Dept Microbiol & Mol Biol, Provo, UT 84602 USA. [Lusso, Paolo] NIAID, Immunoregulat Lab, NIH, Bethesda, MD 20892 USA. RP Lusso, P (reprint author), NIAID, Immunoregulat Lab, NIH, Bldg 10, Bethesda, MD 20892 USA. EM plusso@niaid.nih.gov RI Horvat, Branka/M-3504-2014 OI Horvat, Branka/0000-0003-0578-7765 FU Intramural Research Program of the NIAID; NIH; HHV-6 Foundation; INSERM and ARSEP, France FX This work was supported in part by the Intramural Research Program of the NIAID, NIH (PL), the HHV-6 Foundation (BKB) and the INSERM and ARSEP, France (BFI). NR 27 TC 2 Z9 2 U1 0 U2 3 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 DEC PY 2014 VL 9 BP 97 EP 103 DI 10.1016/j.coviro.2014.09.012 PG 7 WC Virology SC Virology GA AX5IC UT WOS:000346958700017 PM 25462440 ER PT J AU Leibovitch, EC Jacobson, S AF Leibovitch, Emily C. Jacobson, Steven TI Evidence linking HHV-6 with multiple sclerosis: an update SO CURRENT OPINION IN VIROLOGY LA English DT Article ID HUMAN-HERPESVIRUS 6; POLYMERASE-CHAIN-REACTION; EPSTEIN-BARR-VIRUS; INTERFERON-BETA; DISEASE PROGRESSION; CEREBROSPINAL-FLUID; OLIGOCLONAL BANDS; CROSS-REACTIVITY; DNA-SEQUENCES; BRAIN-TISSUE AB Following reports of elevated antiviral antibodies in MS patient sera and viral DNA detection in MS plaques nearly two decades ago, the neurovirology community has actively explored how herpesviruses such as HHV-6 might be involved in MS disease pathogenesis. Though findings across the field are non-uniform, an emerging consensus of viral correlates with disease course and evidence of HHV-6-specific immune responses in the CNS provide compelling evidence for a role, direct or indirect, of this virus in MS. Ultimately, the only way to demonstrate the involvement, or lack thereof, of HHV-6 or other herpesviruses in this disease is through a controlled clinical trial of an efficacious antiviral drug. C1 [Leibovitch, Emily C.; Jacobson, Steven] NINDS, Neuroimmunol Branch, NIH, Bethesda, MD 20892 USA. [Leibovitch, Emily C.] George Washington Univ, Sch Med & Hlth Sci, Inst Biomed Sci, Washington, DC 20052 USA. RP Jacobson, S (reprint author), NINDS, Neuroimmunol Branch, NIH, Bldg 36,Rm 4D04, Bethesda, MD 20892 USA. EM jacobsons@ninds.nih.gov FU National Institutes of Health; National Institute of Neurologic Disease and Stroke (NINDS) FX Funding was provided by the intramural program of the National Institutes of Health, National Institute of Neurologic Disease and Stroke (NINDS). We thank Bridgette Jeanne Billioux and Breanna Caruso for critical reading of the manuscript. NR 52 TC 14 Z9 15 U1 1 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 DEC PY 2014 VL 9 BP 127 EP 133 DI 10.1016/j.coviro.2014.09.016 PG 7 WC Virology SC Virology GA AX5IC UT WOS:000346958700021 PM 25462444 ER PT J AU Boffetta, P Bobak, M Borsch-Supan, A Brenner, H Eriksson, S Grodstein, F Jansen, E Jenab, M Juerges, H Kampman, E Kee, F Kuulasmaa, K Park, Y Tjonneland, A van Duijn, C Wilsgaard, T Wolk, A Trichopoulos, D Bamia, C Trichopoulou, A AF Boffetta, Paolo Bobak, Martin Borsch-Supan, Axel Brenner, Hermann Eriksson, Sture Grodstein, Fran Jansen, Eugene Jenab, Mazda Juerges, Hendrik Kampman, Ellen Kee, Frank Kuulasmaa, Kari Park, Yikyung Tjonneland, Anne van Duijn, Cornelia Wilsgaard, Tom Wolk, Alicja Trichopoulos, Dimitrios Bamia, Christina Trichopoulou, Antonia TI The Consortium on Health and Ageing: Network of Cohorts in Europe and the United States (CHANCES) project-design, population and data harmonization of a large-scale, international study SO EUROPEAN JOURNAL OF EPIDEMIOLOGY LA English DT Article DE Cohort; Ageing; Elderly; Meta-analysis ID OSTEOPOROTIC FRACTURES; CARDIOVASCULAR-DISEASE; LIFE-STYLE; EPIDEMIOLOGY; MORTALITY; WOMEN; DIET; CONSUMPTION; DISABILITY; CANCER AB There is a public health demand to prevent health conditions which lead to increased morbidity and mortality among the rapidly-increasing elderly population. Data for the incidence of such conditions exist in cohort studies worldwide, which, however, differ in various aspects. The Consortium on Health and Ageing: Network of Cohorts in Europe and the United States (CHANCES) project aims at harmonizing data from existing major longitudinal studies for the elderly whilst focussing on cardiovascular diseases, diabetes mellitus, cancer, fractures and cognitive impairment in order to estimate their prevalence, incidence and cause-specific mortality, and identify lifestyle, socioeconomic, and genetic determinants and biomarkers for the incidence of and mortality from these conditions. A survey instrument assessing ageing-related conditions of the elderly will be also developed. Fourteen cohort studies participate in CHANCES with 683,228 elderly (and 150,210 deaths), from 23 European and three non-European countries. So far, 287 variables on health conditions and a variety of exposures, including biomarkers and genetic data have been harmonized. Different research hypotheses are investigated with meta-analyses. The results which will be produced can help international organizations, governments and policy-makers to better understand the broader implications and consequences of ageing and thus make informed decisions. C1 [Boffetta, Paolo; Trichopoulos, Dimitrios; Bamia, Christina; Trichopoulou, Antonia] Hellen Hlth Fdn, Athens 11527, Greece. [Boffetta, Paolo] Icahn Sch Med Mt Sinai, Inst Translat Epidemiol, New York, NY 10029 USA. [Boffetta, Paolo] Icahn Sch Med Mt Sinai, Tisch Canc Inst, New York, NY 10029 USA. [Bobak, Martin] UCL, Dept Epidemiol & Publ Hlth, London WC1E 6BT, England. [Borsch-Supan, Axel] Max Planck Inst Social Law & Social Policy, Munich Ctr Econ Aging, Munich, Germany. [Brenner, Hermann] German Canc Res Ctr, Div Clin Epidemiol & Aging Res, D-69120 Heidelberg, Germany. [Eriksson, Sture] Umea Univ, S-90185 Umea, Sweden. [Grodstein, Fran] Brigham & Womens Hosp, Channing Div Network Med, Boston, MA 02115 USA. [Jansen, Eugene] Natl Inst Publ Hlth & Environm, Ctr Hlth Protect, NL-3720 BA Bilthoven, Netherlands. [Jenab, Mazda] Int Agcy Res Canc IARC WHO, Lyon, France. [Juerges, Hendrik] Univ Wuppertal, Schumpeter Sch Business & Econ, D-42119 Wuppertal, Germany. [Kampman, Ellen] Wageningen Univ, Div Human Nutr, NL-6700 EV Wageningen, Netherlands. [Kee, Frank] Queens Univ Belfast, Inst Clin Sci, UKCRC Ctr Excellence Publ Hlth Northern Ireland, Belfast BT12 6BJ, Antrim, North Ireland. [Kuulasmaa, Kari] Natl Inst Hlth & Welf THL, Chron Dis Epidemiol & Prevent Unit, Helsinki 00271, Finland. [Park, Yikyung] NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. [Tjonneland, Anne] Danish Canc Soc, Res Ctr, DK-2100 Copenhagen O, Denmark. [van Duijn, Cornelia] Erasmus Univ, Med Ctr, Dept Epidemiol, NL-3015 GE Rotterdam, Netherlands. [Wilsgaard, Tom] UIT, Dept Community Med, N-9037 Tromso, Norway. [Wolk, Alicja] Karolinska Inst, Inst Environm Med, S-10401 Stockholm, Sweden. [Trichopoulos, Dimitrios] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. [Trichopoulos, Dimitrios] Acad Athens, Bur Epidemiol Res, Athens, Greece. [Bamia, Christina; Trichopoulou, Antonia] Univ Athens, Sch Med, Dept Hyg Epidemiol & Med Stat, GR-11527 Athens, Greece. RP Trichopoulou, A (reprint author), Hellen Hlth Fdn, 13 Kaisareias & Alexandroupoleos St, Athens 11527, Greece. EM atrichopoulou@hhf-greece.gr RI Kampman, E./H-8057-2014; Brenner, Hermann/B-4627-2017; OI Brenner, Hermann/0000-0002-6129-1572; Kuulasmaa, Kari/0000-0003-2165-1411; Park, Yikyung/0000-0002-6281-489X FU European Community [HEALTH-F3-2010-242244] FX The research leading to these results has received funding from the European Community's Seventh Framework Programme (FP7/2007-2013) DG-RESEARCH under Grant Agreement No. HEALTH-F3-2010-242244. NR 40 TC 16 Z9 16 U1 0 U2 7 PU SPRINGER PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 0393-2990 EI 1573-7284 J9 EUR J EPIDEMIOL JI Eur. J. Epidemiol. PD DEC PY 2014 VL 29 IS 12 BP 929 EP 936 DI 10.1007/s10654-014-9977-1 PG 8 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA AX4PA UT WOS:000346912900006 PM 25504016 ER PT J AU Sinai, P Dozmorov, IM Song, R Schwartzberg, PL Wakeland, EK Wulfing, C AF Sinai, Parisa Dozmorov, Igor M. Song, Ran Schwartzberg, Pamela L. Wakeland, Edward K. Wuelfing, Christoph TI T/B-cell interactions are more transient in response to weak stimuli in SLE-prone mice SO EUROPEAN JOURNAL OF IMMUNOLOGY LA English DT Article DE Actin; Imaging; Immunological synapse; Protein kinase C; Systemic lupus erythematosus ID SYSTEMIC-LUPUS-ERYTHEMATOSUS; GERMINAL-CENTER; PKC-THETA; T-CELLS; SPATIOTEMPORAL ORGANIZATION; IMMUNOLOGICAL SYNAPSE; IMMUNE-RESPONSES; SLAM RECEPTORS; B-CELLS; ACTIVATION AB Changes in immune function during the course of systemic lupus erythematosus (SLE) are well characterized. Class-switched antinuclear antibodies are the hallmark of SLE, and T/B-cell interactions are thus critical. However, changes in immune function contributing to disease susceptibility are unknown. Here, we have analyzed primary T and B cells from a mouse model of SLE prior to the onset of disease. To allow cognate T-cell activation with low affinity, we have developed a lower potency peptide ligand for the OTII TCR. T-and B-cell couples formed less frequently and retained their polarity less efficiently preferentially in response to low-affinity stimulation in SLE-prone mice. This matched decreased recruitment of actin and Vav1 and an enhanced PKC Theta recruitment to the cellular interface in T cells. The induction of the GC B-cell marker GL7 was increased in T/B cell couples from SLE-prone mice when the T-cell numbers were limited. However, the overall gene expression changes were marginal. Taken together, the enhanced cell-couple transience may allow a more efficient sampling of a large number of T/B cell couples, preferentially in response to limiting stimuli, therefore enhancing the immune reactivity in the development of SLE. C1 [Sinai, Parisa; Wuelfing, Christoph] Univ Bristol, Sch Cellular & Mol Med, Bristol BS8 1TD, Avon, England. [Sinai, Parisa; Dozmorov, Igor M.; Song, Ran; Wakeland, Edward K.; Wuelfing, Christoph] UT Southwestern Med Ctr, Dept Immunol, Dallas, TX USA. [Schwartzberg, Pamela L.] NHGRI, NIH, Bethesda, MD 20892 USA. [Wuelfing, Christoph] UT Southwestern Med Ctr, Dept Cell Biol, Dallas, TX USA. RP Wulfing, C (reprint author), Univ Bristol, Sch Cellular & Mol Med, Bristol BS8 1TD, Avon, England. EM Christoph.Wuelfing@bristol.ac.uk FU National Institutes of Health [CA90436]; National Human Genome Research Institute FX This work was supported by grants from the National Institutes of Health (CA90436) and in part by the intramural program of the National Human Genome Research Institute. P.S., E.K.W., and C.W. designed the experiments; P.S., I.M.D., and C.W. executed the experiments; P.L.S. and E.K.W. provided critical mouse strains; P.S. and C.W. wrote the manuscript. NR 37 TC 3 Z9 3 U1 0 U2 5 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0014-2980 EI 1521-4141 J9 EUR J IMMUNOL JI Eur. J. Immunol. PD DEC PY 2014 VL 44 IS 12 BP 3522 EP 3531 DI 10.1002/eji.201444602 PG 10 WC Immunology SC Immunology GA AX1IO UT WOS:000346701200007 PM 25209945 ER PT J AU Brown, PR Odet, F Bortner, CD Eddy, EM AF Brown, Paula R. Odet, Fanny Bortner, Carl D. Eddy, Edward M. TI Reporter Mice Express Green Fluorescent Protein at Initiation of Meiosis in Spermatocytes SO GENESIS LA English DT Article DE spermatogenesis; heat shock protein; variegated gene expression; fluorescence activated cell sorting ID MOUSE SPERMATOGENIC CELLS; TRANSGENIC MICE; SP-10 GENE; CENTRIFUGAL ELUTRIATION; SEDIMENTATION-VELOCITY; STEM-CELLS; PROMOTER; TESTIS; INSULATOR; P70 AB Transgenic mice were generated using a heat shock protein 2 (Hspa2) gene promoter to express green fluorescent protein (GFP) at the beginning of meiotic prophase I in spermatocytes. Expression was confirmed in four lines by in situ fluorescence, immunohistochemistry, western blotting, and PCR assays. The expression and distribution of the GFP and HSPA2 proteins co-localized in spermatocytes and spermatids in three lines, but GFP expression was variegated in one line (F46), being present in some clones of meiotic and post-meiotic germ cells and not in others. Fluorescence activated cell sorting (FACS) was used to isolate purified populations of spermatocytes and spermatids. Although bisulfite sequencing revealed differences in the DNA methylation patterns in the promoter regions of the transgene of the variegated expressing GFP line, a uniformly expressing GFP reporter line, and the Hspa2 gene, these differences did not correlate with variegated expression. The Hspa2-GFP reporter mice provide a novel tool for studies of meiosis by allowing detection of GFP in situ and in isolated spermatogenic cells. They will allow sorting of meiotic and post-meiotic germ cells for characterization of molecular features and correlation of expression of GFP with stage-specific spermatogenic cell proteins and developmental events. genesis 52:976-984, 2014. (c) 2014 Wiley Periodicals, Inc. C1 [Brown, Paula R.; Odet, Fanny; Eddy, Edward M.] NIEHS, Gamete Biol Sect, Reprod & Dev Toxicol Lab, NIH, Res Triangle Pk, NC 27709 USA. [Odet, Fanny] GenOway, Lyon, France. [Bortner, Carl D.] NIEHS, Mol Endocrinol Grp, Lab Signal Transduct, NIH, Res Triangle Pk, NC 27709 USA. RP Eddy, EM (reprint author), NIEHS, Gamete Biol Sect, Reprod & Dev Toxicol Lab, NIH, POB 12233, Res Triangle Pk, NC 27709 USA. EM eddy@niehs.nih.gov FU NIH, National Institute of Environmental Health Sciences FX Supported by the Intramural Research Program of the NIH, National Institute of Environmental Health Sciences NR 28 TC 1 Z9 1 U1 0 U2 5 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1526-954X EI 1526-968X J9 GENESIS JI Genesis PD DEC PY 2014 VL 52 IS 12 BP 976 EP 984 DI 10.1002/dvg.22830 PG 9 WC Developmental Biology; Genetics & Heredity SC Developmental Biology; Genetics & Heredity GA AX1IY UT WOS:000346702100007 PM 25293348 ER PT J AU Bai, HH Guo, XS Zhang, D Narisu, N Bu, JJ Jirimutu, J Liang, F Zhao, X Xing, YP Wang, DZ Li, TD Zhang, YR Guan, BZ Yang, XK Yang, ZL Shuangshan, S Su, Z Wu, HG Li, WJ Chen, M Zhu, SL Bayinnamula, B Chang, YQ Gao, Y Lan, TM Suyalatu, S Huang, H Su, Y Chen, YJ Li, WQ Yang, X Feng, Q Wang, J Yang, HM Wang, J Wu, QZ Yin, Y Zhou, HM AF Bai, Haihua Guo, Xiaosen Zhang, Dong Narisu, Narisu Bu, Junjie Jirimutu, Jirimutu Liang, Fan Zhao, Xiang Xing, Yanping Wang, Dingzhu Li, Tongda Zhang, Yanru Guan, Baozhu Yang, Xukui Yang, Zili Shuangshan, Shuangshan Su, Zhe Wu, Huiguang Li, Wenjing Chen, Ming Zhu, Shilin Bayinnamula, Bayinnamula Chang, Yuqi Gao, Ying Lan, Tianming Suyalatu, Suyalatu Huang, Hui Su, Yan Chen, Yujie Li, Wenqi Yang, Xu Feng, Qiang Wang, Jian Yang, Huanming Wang, Jun Wu, Qizhu Yin, Ye Zhou, Huanmin TI The Genome of a Mongolian Individual Reveals the Genetic Imprints of Mongolians on Modern Human Populations SO GENOME BIOLOGY AND EVOLUTION LA English DT Article DE Mongolian genome; de novo assembly; genetic variations; patrilineal origin; genetic imprints ID Y-CHROMOSOME EVIDENCE; HUMAN MITOCHONDRIAL-DNA; SEQUENCING DATA; CARNITINE DEFICIENCY; WIDE PATTERNS; EASTERN ASIA; NEW-WORLD; HISTORY; PROTEIN; DATABASE AB Mongolians have played a significant role in modern human evolution, especially after the rise of Genghis Khan (1162[?]-1227). Although the social cultural impacts of Genghis Khan and the Mongolian population have been well documented, explorations of their genome structure and genetic imprints on other human populations have been lacking. We here present the genome of a Mongolian male individual. The genome was de novo assembled using a total of 130.8-fold genomic data produced from massively parallel whole-genome sequencing. We identified high-confidence variation sets, including 3.7 million single nucleotide polymorphisms (SNPs) and 756,234 short insertions and deletions. Functional SNP analysis predicted that the individual has a pathogenic risk for carnitine deficiency. We located the patrilineal inheritance of the Mongolian genome to the lineage D3a through Y haplogroup analysis and inferred that the individual has a common patrilineal ancestor with Tibeto-Burman populations and is likely to be the progeny of the earliest settlers in East Asia. We finally investigated the genetic imprints of Mongolians on other human populations using different approaches. We found varying degrees of gene flows between Mongolians and populations living in Europe, South/Central Asia, and the Indian subcontinent. The analyses demonstrate that the genetic impacts of Mongolians likely resulted from the expansion of the Mongolian Empire in the 13th century. The genome will be of great help in further explorations of modern human evolution and genetic causes of diseases/traits specific to Mongolians. C1 [Bai, Haihua; Jirimutu, Jirimutu; Wang, Dingzhu; Shuangshan, Shuangshan; Wu, Huiguang; Chen, Ming; Bayinnamula, Bayinnamula; Gao, Ying; Suyalatu, Suyalatu; Chen, Yujie; Wu, Qizhu] Inner Mongolia Univ Nationalities, Tongliao, Peoples R China. [Guo, Xiaosen; Bu, Junjie; Liang, Fan; Zhao, Xiang; Li, Tongda; Yang, Xukui; Su, Zhe; Li, Wenjing; Zhu, Shilin; Chang, Yuqi; Lan, Tianming; Huang, Hui; Su, Yan; Li, Wenqi; Yang, Xu; Feng, Qiang; Wang, Jian; Yang, Huanming; Wang, Jun; Yin, Ye] BGI Shenzhen, Shenzhen, Peoples R China. [Guo, Xiaosen; Feng, Qiang; Wang, Jun] Univ Copenhagen, Dept Biol, DK-1168 Copenhagen, Denmark. [Zhang, Dong; Xing, Yanping; Zhang, Yanru; Yang, Zili; Zhou, Huanmin] Inner Mongolia Agr Univ, Inner Mongolia Autonomous Reg Key Lab Biomanufact, Hohhot, Peoples R China. [Narisu, Narisu] NHGRI, Med Genom & Metab Genet Branch, NIH, Bethesda, MD 20892 USA. [Bu, Junjie; Yang, Huanming] Univ Elect Sci & Technol China, Sch Life Sci & Technol, Minist Educ, Key Lab NeuroInformat, Chengdu 610054, Peoples R China. [Li, Tongda] S China Univ Technol, Sch Biosci & Bioengn, Guangzhou, Guangdong, Peoples R China. [Guan, Baozhu] Inner Mongolia Int Mongolian Hosp, Hohhot, Peoples R China. [Shuangshan, Shuangshan] Baotou Normal Coll, Baotou, Peoples R China. [Chen, Ming] Zhejiang Univ, Coll Life Sci, Dept Bioinformat, Hangzhou 310003, Zhejiang, Peoples R China. [Wang, Jian; Yang, Huanming] James D Watson Inst Genome Sci, Hangzhou, Zhejiang, Peoples R China. [Wang, Jun] Univ Copenhagen, Ctr Basic Metab Res, Novo Nordisk Fdn, DK-1168 Copenhagen, Denmark. [Wang, Jun] King Abdulaziz Univ, Jeddah 21413, Saudi Arabia. [Wang, Jun] Aarhus Univ, Ctr iSequencing, DK-8000 Aarhus C, Denmark. RP Wu, QZ (reprint author), Inner Mongolia Univ Nationalities, Tongliao, Peoples R China. EM qizhu_wu@sohu.com; yinye@genomics.cn; huanminzhou@gmail.com RI Wang, Jun/C-8434-2016; Wang, Jun/B-9503-2016 OI Wang, Jun/0000-0002-8540-8931; Wang, Jun/0000-0002-2113-5874 FU National Basic Research Program of China (973 program) [2011CB809201, 2011CB809202, 2011CB809203]; Chinese 863 Program [2012AA02A201]; National Natural Science Foundation of China [30890032, 31161130357, 81060098, 81160101]; Foundation of the Inner Mongolia Department of Education [NJZY13169]; Shenzhen Municipal Government of China [ZYC200903240080A, ZYC201105170397A]; NHGRI [1ZIAHG000024]; National Institute of Health (NIH) FX The authors sincerely thank our sample donor for generously contributing his blood. This project was supported by the National Basic Research Program of China (973 program no. 2011CB809201, 2011CB809202, and 2011CB809203), the Chinese 863 Program (2012AA02A201), the National Natural Science Foundation of China (30890032, 31161130357, 81060098, and 81160101), Foundation of the Inner Mongolia Department of Education (NJZY13169), and the Shenzhen Municipal Government of China (grants ZYC200903240080A and ZYC201105170397A). It was also supported by the intramural program of NHGRI (1ZIAHG000024), the National Institute of Health (NIH) to N.N. The authors are indebted to the Mongolian historians and anthropologists who contributed to this work, but are not included in the author list, including Dr Yuqing Bao, Dr Ming Chen, Dr Yongchun Fu, and others. They sincerely thank Dr David Reich for generously providing the genotype data of India populations. They thank Dr Francis S. Collins, Dr Steve C.J. Parker, Dr Lawrence Brody, and Dr Kevin Stuart for helpful advice, comments, and editing. They also thank two anonymous reviewers for critical comments. The authors declare that they have no competing interest. NR 70 TC 3 Z9 3 U1 3 U2 19 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 1759-6653 J9 GENOME BIOL EVOL JI Genome Biol. Evol. PD DEC PY 2014 VL 6 IS 12 BP 3122 EP 3136 DI 10.1093/gbe/evu242 PG 15 WC Evolutionary Biology; Genetics & Heredity SC Evolutionary Biology; Genetics & Heredity GA AX5YO UT WOS:000347000800001 PM 25377941 ER PT J AU Manasanch, EE Korde, N Mailankody, S Tageja, N Bhutani, M Roschewski, M Landgren, O AF Manasanch, Elisabet E. Korde, Neha Mailankody, Sham Tageja, Nishant Bhutani, Manisha Roschewski, Mark Landgren, Ola TI Smoldering multiple myeloma: special considerations surrounding treatment on versus off clinical trials SO HAEMATOLOGICA LA English DT Editorial Material ID STEM-CELL TRANSPLANTATION; MONOCLONAL GAMMOPATHY; UNDETERMINED SIGNIFICANCE; COMPLETE RESPONSE; PROGRESSION; THERAPY; RISK C1 [Manasanch, Elisabet E.] Univ Texas MD Anderson Canc Ctr, Dept Lymphoma Myeloma, Houston, TX 77030 USA. [Korde, Neha; Landgren, Ola] Mem Sloan Kettering Canc Ctr, Myeloma Serv, New York, NY 10021 USA. [Mailankody, Sham; Tageja, Nishant; Bhutani, Manisha; Roschewski, Mark] NCI, Multiple Myeloma Sect, Lymphoid Malignancies Branch, NIH, Bethesda, MD 20892 USA. RP Manasanch, EE (reprint author), Univ Texas MD Anderson Canc Ctr, Dept Lymphoma Myeloma, Houston, TX 77030 USA. EM EEManasanch@mdanderson.org; landgrec@mskcc.org NR 17 TC 2 Z9 2 U1 0 U2 0 PU FERRATA STORTI FOUNDATION PI PAVIA PA VIA GIUSEPPE BELLI 4, 27100 PAVIA, ITALY SN 0390-6078 J9 HAEMATOLOGICA JI Haematologica PD DEC PY 2014 VL 99 IS 12 BP 1769 EP 1771 DI 10.3324/haematol.2014.107516 PG 3 WC Hematology SC Hematology GA AX6EP UT WOS:000347016400001 PM 25472951 ER PT J AU Kim, SY Le Rademacher, J Antin, JH Anderlini, P Ayas, M Battiwalla, M Carreras, J Kurtzberg, J Nakamura, R Eapen, M Deeg, HJ AF Kim, Sung-Yong Le Rademacher, Jennifer Antin, Joseph H. Anderlini, Paolo Ayas, Mouhab Battiwalla, Minoo Carreras, Jeanette Kurtzberg, Joanne Nakamura, Ryotaro Eapen, Mary Deeg, H. Joachim TI Myelodysplastic syndrome evolving from aplastic anemia treated with immunosuppressive therapy: efficacy of hematopoietic stem cell transplantation SO HAEMATOLOGICA LA English DT Article ID ACUTE MYELOID-LEUKEMIA; UNRELATED DONOR TRANSPLANTATION; ANTITHYMOCYTE GLOBULIN; TELOMERE LENGTH; RISK-FACTORS; CYCLOSPORINE; ASSOCIATION; KARYOTYPE; RECIPIENT; CHILDREN AB A proportion of patients with aplastic anemia who are treated with immunosuppressive therapy develop clonal hematologic disorders, including post-aplastic anemia myelodysplastic syndrome. Many will proceed to allogeneic hematopoietic stem cell transplantation. We identified 123 patients with post-aplastic anemia myelodysplastic syndrome who from 1991 through 2011 underwent allogeneic hematopoietic stem cell transplantation, and in a matched-pair analysis compared outcome to that in 393 patients with de novo myelodysplastic syndrome. There was no difference in overall survival. There were no significant differences with regard to 5-year probabilities of relapse, non-relapse mortality, relapse-free survival and overall survival; these were 14%, 40%, 46% and 49% for post-aplastic anemia myelodysplastic syndrome, and 20%, 33%, 47% and 49% for de novo myelodysplastic syndrome, respectively. In multivariate analysis, relapse (hazard ratio 0.71; P=0.18), non-relapse mortality (hazard ratio 1.28; P=0.18), relapse-free survival (hazard ratio 0.97; P=0.80) and overall survival (hazard ratio 1.02; P=0.88) of post-aplastic anemia myelodysplastic syndrome were similar to those of patients with de novo myelodysplastic syndrome. Cytogenetic risk was independently associated with overall survival in both groups. Thus, transplant success in patients with post-aplastic anemia myelodysplastic syndrome was similar to that in patients with de novo myelodysplastic syndrome, and cytogenetics was the only significant prognostic factor for post-aplastic anemia myelodysplastic syndrome patients. C1 [Kim, Sung-Yong; Deeg, H. Joachim] Fred Hutchinson Canc Res Ctr, Div Clin Res, Seattle, WA 98104 USA. [Kim, Sung-Yong] KonKuk Univ, Sch Med, Med Ctr, Seoul, South Korea. [Le Rademacher, Jennifer; Carreras, Jeanette; Eapen, Mary] Med Coll Wisconsin, Ctr Int Blood & Marrow Transplant Res, Dept Med, Milwaukee, WI 53226 USA. [Le Rademacher, Jennifer] Med Coll Wisconsin, Div Biostat, Milwaukee, WI 53226 USA. [Antin, Joseph H.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Anderlini, Paolo] Univ Texas MD Anderson Canc Ctr, Dept Stem Cell Transplantat & Cellular Therapy, Houston, TX 77030 USA. [Ayas, Mouhab] King Faisal Specialist Hosp & Res Ctr, Dept Pediat Hematol Oncol, Riyadh 11211, Saudi Arabia. [Carreras, Jeanette] NHLBI, Hematol Branch, NIH, Bethesda, MD 20892 USA. [Kurtzberg, Joanne] Duke Univ, Med Ctr, Dept Pediat Pediat Blood & Marrow Transplant, Durham, NC USA. [Nakamura, Ryotaro] City Hope Natl Med Ctr, Duarte, CA 91010 USA. RP Deeg, HJ (reprint author), Fred Hutchinson Canc Res Ctr, Div Clin Res, 1124 Columbia St, Seattle, WA 98104 USA. EM jdeeg@fhcrc.org FU National Cancer Institute (NCI) [U24-CA076518]; National Heart, Lung and Blood Institute (NHLBI); National Institute of Allergy and Infectious Diseases (NIAID); NHLBI [5U10HL069294]; NCI; Health Resources and Services Administration (HRSA/DHHS) [HHSH250201200016C]; Office of Naval Research [N00014-13-10039, N00014-14-1-0028]; Actinium Pharmaceuticals; Allos Therapeutics, Inc.; Amgen, Inc.; [HL036444]; [HL095999]; [CA015704] FX The CIBMTR which is supported by Public Health Service Grant/Cooperative Agreement U24-CA076518 from the National Cancer Institute (NCI), the National Heart, Lung and Blood Institute (NHLBI) and the National Institute of Allergy and Infectious Diseases (NIAID); a Grant/Cooperative Agreement 5U10HL069294 from NHLBI and NCI; a contract HHSH250201200016C with Health Resources and Services Administration (HRSA/DHHS); two Grants N00014-13-10039 and N00014-14-1-0028 from the Office of Naval Research; and grants from *Actinium Pharmaceuticals; Allos Therapeutics, Inc.; *Amgen, Inc.; anonymous donation to the Medical College of Wisconsin; Ariad; Be the Match Foundation; Blue Cross and Blue Shield Association; *Celgene Corporation; Chimerix, Inc.; Fred Hutchinson Cancer Research Center; Fresenius-Biotech North America, Inc.; *Gamida Cell Teva Joint Venture Ltd.; Genentech, Inc.;*Gentium SpA; Genzyme Corporation; GlaxoSmithKline; Health Research, Inc. Roswell Park Cancer Institute; HistoGenetics, Inc.; Incyte Corporation; Jeff Gordon Children's Foundation; Kiadis Pharma; The Leukemia & Lymphoma Society; Medac GmbH; The Medical College of Wisconsin; Merck & Co, Inc.; Millennium: The Takeda Oncology Co.; *Milliman USA, Inc.; *Miltenyi Biotec, Inc.; National Marrow Donor Program; Onyx Pharmaceuticals; Optum Healthcare Solutions, Inc.; Osiris Therapeutics, Inc.; Otsuka America Pharmaceutical, Inc.; Perkin Elmer, Inc.; *Remedy Informatics; *Sanofi US; Seattle Genetics; Sigma-Tau Pharmaceuticals; Soligenix, Inc.; St. Baldrick's Foundation; StemCyte, A Global Cord Blood Therapeutics Co.; Stemsoft Software, Inc.; Swedish Orphan Biovitrum; *Tarix Pharmaceuticals; *TerumoBCT; *Teva Neuroscience, Inc.; *THERAKOS, Inc.; University of Minnesota; University of Utah; and *Wellpoint, Inc. The views expressed in this article do not reflect the official policy or position of the National Institute of Health, the Department of the Navy, the Department of Defense, Health Resources and Services Administration (HRSA) or any other agency of the U.S. Government. *Corporate Members. SY K and HJD were supported by grants HL036444, HL095999 and CA015704. NR 28 TC 3 Z9 3 U1 2 U2 6 PU FERRATA STORTI FOUNDATION PI PAVIA PA VIA GIUSEPPE BELLI 4, 27100 PAVIA, ITALY SN 0390-6078 J9 HAEMATOLOGICA JI Haematologica PD DEC PY 2014 VL 99 IS 12 BP 1868 EP 1875 DI 10.3324/haematol.2014.108977 PG 8 WC Hematology SC Hematology GA AX6EP UT WOS:000347016400013 PM 25107891 ER PT J AU Jelacic, TM Chabot, DJ Bozue, JA Tobery, SA West, MW Moody, K Yang, D Oppenheim, JJ Friedlander, AM AF Jelacic, Tanya M. Chabot, Donald J. Bozue, Joel A. Tobery, Steven A. West, Michael W. Moody, Krishna Yang, De Oppenheim, Joost J. Friedlander, Arthur M. TI Exposure to Bacillus anthracis Capsule Results in Suppression of Human Monocyte-Derived Dendritic Cells (vol 82, pg 3405, 2014) SO INFECTION AND IMMUNITY LA English DT Correction C1 [Jelacic, Tanya M.; Chabot, Donald J.; Bozue, Joel A.; Tobery, Steven A.; West, Michael W.; Friedlander, Arthur M.] US Army, Med Res Inst Infect Dis, Frederick, MD 21702 USA. [Yang, De; Oppenheim, Joost J.] Frederick Natl Lab Canc Res, Mol Immunoregulat Lab, Frederick, MD USA. [Moody, Krishna] Boston Univ, Sch Med, Dept Microbiol, Boston, MA 02118 USA. RP Jelacic, TM (reprint author), US Army, Med Res Inst Infect Dis, Frederick, MD 21702 USA. NR 1 TC 0 Z9 0 U1 0 U2 1 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0019-9567 EI 1098-5522 J9 INFECT IMMUN JI Infect. Immun. PD DEC PY 2014 VL 82 IS 12 BP 5347 EP 5347 DI 10.1128/IAI.02665-14 PG 1 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA AX5HZ UT WOS:000346958400043 ER PT J AU Zhang, XX Ito, Y Liang, JR Liu, JL He, J Sun, WJ AF Zhang, Xin-xin Ito, Yoichiro Liang, Jin-ru Liu, Jian-li He, Jiao Sun, Wen-ji TI Therapeutic effects of total steroid saponin extracts from the rhizome of Dioscorea zingiberensis CHWright in Freund's complete adjuvant induced arthritis in rats SO INTERNATIONAL IMMUNOPHARMACOLOGY LA English DT Article DE Dioscorea zingiberensis CHWright; Total steroid saponins; Adjuvant-induced arthritis; Lipopolysaccharide; NF-kappa B ID COLLAGEN-INDUCED ARTHRITIS; KAPPA-B; INFLAMMATORY MEDIATORS; RHEUMATOID-ARTHRITIS; ACTIVATION; SUPPRESSES; IDENTIFICATION; PATHWAY; DIOSCIN; WRIGHT AB The aim of our present study is to explore the anti-arthritic potential effect of total steroid saponins (TSSNs) extracted from the rhizome of Dioscorea zingiberensis C.H.Wright (DZW) and to investigate the underlying mechanisms. This work was performed using adjuvant-induced arthritis (AIA) rats in vivo and lipopolysaccharide (LPS) simulated 264.7 macrophage cells in vitro. In ALA-induced arthritic rats, TSSN significantly alleviated the arthritic progression through evaluating arthritic score, immune organ indexes, paw swelling, and body weight This phenomenon was well correlated with significant suppression of the overproduction of inflammation cytokines (IL-1, IL-1 beta, IL-6, and TNF-alpha.), oxidant stress makers (MDA and NO), eicosanoids (LTB4 and PGE(2)), and inflammatory enzymes (5-LOX and COX-2) versus the ALA rats without treatment. On the contrary, the release of SOD and IL-10 was profoundly increased. What's more, TSSN could obviously ameliorate the translocation of NF-kappa B to the nucleus through phosphorylation of the p65 and I kappa B alpha in vivo and in vitro. The current findings demonstrated that TSSN could protect the injured ankle joint from further deterioration and exert its satisfactory anti-arthritis properties through anti-inflammatory and anti-oxidant effects via inactivating the NF-kappa B signal pathway. This research implies that DZW may be a useful therapeutic agent for the treatment of human arthritis. (C) 2014 Published by Elsevier B.V. C1 [Zhang, Xin-xin; Liang, Jin-ru; Liu, Jian-li; He, Jiao; Sun, Wen-ji] NW Univ Xian, Biomed Key Lab Shaanxi Prov, Xian 710069, Peoples R China. [Ito, Yoichiro] NHLBI, Lab Bioseparat Technol, Biochem & Biophys Ctr, NIH, Bethesda, MD 20892 USA. RP Ito, Y (reprint author), NHLBI, Lab Bioseparat Technol, Biochem & Biophys Ctr, NIH, Bldg 10, Bethesda, MD 20892 USA. EM itoy@nhlbi.nih.gov; guoxiaolizhang@163.com FU Intramural NIH HHS [Z99 HL999999] NR 33 TC 5 Z9 5 U1 1 U2 18 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 1567-5769 EI 1878-1705 J9 INT IMMUNOPHARMACOL JI Int. Immunopharmacol. PD DEC PY 2014 VL 23 IS 2 BP 407 EP 416 DI 10.1016/j.intimp.2014.07.018 PG 10 WC Immunology; Pharmacology & Pharmacy SC Immunology; Pharmacology & Pharmacy GA AX5GF UT WOS:000346954000006 PM 25066758 ER PT J AU Bode, C Wang, J Klinman, DM AF Bode, Christian Wang, Jing Klinman, Dennis M. TI Suppressive oligodeoxynucleotides promote the generation of regulatory T cells by inhibiting STAT1 phosphorylation SO INTERNATIONAL IMMUNOPHARMACOLOGY LA English DT Article DE Suppressive oligonucleotides; Regulatory T cells; STAT transcription factors ID TRANSCRIPTION FACTOR FOXP3; IMMUNE TOLERANCE; COMMENSAL DNA; TTAGGG MOTIFS; INDUCTION; EFFECTOR; MICE; OLIGONUCLEOTIDES; ACTIVATION; ANTIGEN AB Suppressive oligodeoxynucleotides (Sup ODN) express repetitive TTAGGG motifs that have proven useful in the treatment/prevention of numerous inflammatory and autoimmune diseases. The mechanism underlying the immunosuppressive activity of Sup ODN is incompletely understood. Regulatory T cells (T-reg) Play a key role in controlling a variety of pathologic autoimmune responses. T-reg are generated from activated CD4(+) T cells in a process that involves the phosphorylation of STAT family members. Current studies demonstrate that Sup ODN promote the differentiation of CD4(+)CD25(-) T cells into functionally active iT(reg) in vitro. When administered in vivo, Sup ODN promote the generation of iT(reg) in response to peptide challenge. Central to this effect is the ability of Sup ODN to block the phosphorylation of STAT1. These findings clarify the mechanism underlying the therapeutic activity of Sup ODN and support their use in T-reg-based immunotherapy. Published by Elsevier B.V. All rights reserved. C1 [Bode, Christian; Wang, Jing; Klinman, Dennis M.] NCI, Ctr Canc Res, Canc & Inflammat Program, Frederick, MD 21702 USA. [Bode, Christian] Univ Hosp Bonn, Dept Anesthesiol & Intens Care Med, Bonn, Germany. RP Klinman, DM (reprint author), NCI, CCR, Bldg 567 Rm 205, Frederick, MD 21702 USA. EM klinmand@mail.nih.gov FU National Cancer Institute of the National Institutes of Health FX This research was supported by the Intramural Research Program of the National Cancer Institute of the National Institutes of Health. NR 48 TC 3 Z9 3 U1 0 U2 5 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 1567-5769 EI 1878-1705 J9 INT IMMUNOPHARMACOL JI Int. Immunopharmacol. PD DEC PY 2014 VL 23 IS 2 BP 516 EP 522 DI 10.1016/j.intimp.2014.09.027 PG 7 WC Immunology; Pharmacology & Pharmacy SC Immunology; Pharmacology & Pharmacy GA AX5GF UT WOS:000346954000020 PM 25311665 ER PT J AU Yang, J Lernmark, A Uusitalo, UM Lynch, KF Veijola, R Winkler, C Larsson, HE Rewers, M She, JX Ziegler, AG Simell, OG Hagopian, WA Akolkar, B Krischer, JP Vehik, K AF Yang, J. Lernmark, A. Uusitalo, U. M. Lynch, K. F. Veijola, R. Winkler, C. Larsson, H. E. Rewers, M. She, J-X Ziegler, A. G. Simell, O. G. Hagopian, W. A. Akolkar, B. Krischer, J. P. Vehik, K. CA TEDDY Study Grp TI Prevalence of obesity was related to HLA-DQ in 2-4-year-old children at genetic risk for type 1 diabetes SO INTERNATIONAL JOURNAL OF OBESITY LA English DT Article DE body mass index; HLA genotype; type 1 diabetes; pediatric; autoantibodies ID BODY-MASS INDEX; INCREASED LINEAR GROWTH; ACCELERATOR HYPOTHESIS; ENVIRONMENTAL DETERMINANTS; FINNISH CHILDREN; CELIAC-DISEASE; AGE; DIAGNOSIS; OVERWEIGHT; GENOTYPES AB OBJECTIVES: Body size is postulated to modulate type 1 diabetes as either a trigger of islet autoimmunity or an accelerator to clinical onset after seroconversion. As overweight and obesity continue to rise among children, the aim of this study was to determine whether human leukocyte antigen DQ (HLA-DQ) genotypes may be related to body size among children genetically at risk for type 1 diabetes. METHODS: Repeated measures of weight and height were collected from 5969 children 2-4 years of age enrolled in The Environmental Determinants of Diabetes in the Young prospective study. Overweight and obesity was determined by the International Obesity Task Force cutoff values that correspond to body mass index (BMI) of 25 and 30 kg m(-2) at age 18. RESULTS: The average BMI was comparable across specific HLA genotypes at every age point. The proportion of overweight was not different by HLA, but percent obesity varied by age with a decreasing trend among DQ2/8 carriers (P for trend = 0.0315). A multivariable regression model suggested DQ2/2 was associated with higher obesity risk at age 4 (odds ratio, 2.41; 95% confidence interval, 1.21-4.80) after adjusting for the development of islet autoantibody and/or type 1 diabetes. CONCLUSIONS: The HLA-DQ2/2 genotype may predispose to obesity among 2-4-year-old children with genetic risk for type 1 diabetes. C1 [Yang, J.; Uusitalo, U. M.; Lynch, K. F.; Krischer, J. P.; Vehik, K.] Univ S Florida, Dept Pediat, Morsani Coll Med, Pediat Epidemiol Ctr, Tampa, FL 33612 USA. [Lernmark, A.; Larsson, H. E.] Lund Univ, CRC, Skane Univ Hosp SUS, Dept Clin Sci, Malmo, Sweden. [Veijola, R.] Univ Oulu, Dept Pediat, Inst Clin Med, SF-90100 Oulu, Finland. [Winkler, C.; Ziegler, A. G.] Helmholtz Zentrum Munchen, Inst Diabet Res, Neuherberg, Germany. [Winkler, C.; Ziegler, A. G.] Tech Univ Munich, Klinikum Rechts Isar, Neuherberg, Germany. [Winkler, C.; Ziegler, A. G.] Forschergrp Diabet eV, Neuherberg, Germany. [Rewers, M.] Univ Colorado, Barbara Davis Ctr Childhood Diabet, Aurora, CO USA. [She, J-X] Georgia Regents Univ, Med Coll Georgia, Ctr Biotechnol & Genom Med, Augusta, GA USA. [Simell, O. G.] Univ Turku, Dept Pediat, Turku, Finland. [Hagopian, W. A.] Pacific Northwest Diabet Res Inst, Seattle, WA USA. [Akolkar, B.] NIDDK, Bethesda, MD USA. RP Yang, J (reprint author), Univ S Florida, Dept Pediat, Morsani Coll Med, Pediat Epidemiol Ctr, 3650 Spectrum Blvd,Suite 100, Tampa, FL 33612 USA. EM jimin.yang@epi.usf.edu RI Ziegler, Anette-Gabriele/M-4614-2014; OI Ziegler, Anette-Gabriele/0000-0002-6290-5548; Elding Larsson, Helena/0000-0003-3306-1742 FU National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) [U01 DK63829, U01 DK63861, U01 DK63821, U01 DK63865, U01 DK63863, U01 DK63836, U01 DK63790, UC4 DK63829, UC4 DK63861, UC4 DK63821, UC4 DK63865, UC4 DK63863, UC4 DK63836, UC4 DK95300, HHSN267200700014C]; National Institute of Allergy and Infectious Diseases (NIAID); National Institute of Child Health and Human Development (NICHD); National Institute of Environmental Health Sciences (NIEHS); Juvenile Diabetes Research Foundation (JDRF); Centers for Disease Control and Prevention (CDC) FX This study was funded by U01 DK63829, U01 DK63861, U01 DK63821, U01 DK63865, U01 DK63863, U01 DK63836, U01 DK63790, UC4 DK63829, UC4 DK63861, UC4 DK63821, UC4 DK63865, UC4 DK63863, UC4 DK63836 and UC4 DK95300 and Contract No. HHSN267200700014C from the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK), National Institute of Allergy and Infectious Diseases (NIAID), National Institute of Child Health and Human Development (NICHD), National Institute of Environmental Health Sciences (NIEHS), Juvenile Diabetes Research Foundation (JDRF), and Centers for Disease Control and Prevention (CDC). NR 42 TC 0 Z9 0 U1 4 U2 5 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0307-0565 EI 1476-5497 J9 INT J OBESITY JI Int. J. Obes. PD DEC PY 2014 VL 38 IS 12 BP 1491 EP 1496 DI 10.1038/ijo.2014.55 PG 6 WC Endocrinology & Metabolism; Nutrition & Dietetics SC Endocrinology & Metabolism; Nutrition & Dietetics GA AX7PL UT WOS:000347107400002 PM 24694666 ER PT J AU Chrysovergis, K Wang, X Kosak, J Lee, SH Kim, JS Foley, JF Travlos, G Singh, S Baek, SJ Eling, TE AF Chrysovergis, K. Wang, X. Kosak, J. Lee, S-H Kim, J. S. Foley, J. F. Travlos, G. Singh, S. Baek, S. J. Eling, T. E. TI NAG-1/GDF-15 prevents obesity by increasing thermogenesis, lipolysis and oxidative metabolism SO INTERNATIONAL JOURNAL OF OBESITY LA English DT Article DE NAG-1/GDF-15; insulin resistance; BAT; thermogenesis; lipolysis ID BROWN ADIPOSE-TISSUE; DIET-INDUCED OBESITY; TGF-BETA SUPERFAMILY; MACROPHAGE INHIBITORY CYTOKINE-1; INSULIN-RESISTANCE; ENERGY-EXPENDITURE; ADIPOCYTE DIFFERENTIATION; ENDOCRINE ORGAN; SENSITIVITY; MICE AB OBJECTIVE: Obesity is a major health problem associated with high morbidity and mortality. NSAID-activated gene (NAG-1) is a TGF-beta superfamily member reported to alter adipose tissue levels in mice. We investigated whether hNAG-1 acts as a regulator of adiposity and energy metabolism. DESIGN/SUBJECTS: hNAG-1 mice, ubiquitously expressing hNAG-1, were placed on a control or high-fat diet for 12 weeks. hNAG-1-expressing B16/F10 melanoma cells were used in a xenograft model to deliver hNAG-1 to obese C57BL/6 mice. RESULTS: As compared with wild-type littermates, transgenic hNAG-1 mice have less white fat and brown fat despite equivalent food intake, improved glucose tolerance, lower insulin levels and are resistant to dietary-and genetic-induced obesity. hNAG-1 mice are more metabolically active with higher energy expenditure. Obese C57BL/6 mice treated with hNAG-1-expressing xenografts show decreases in adipose tissue and serum insulin levels. hNAG-1 mice and obese mice treated with hNAG-1-expressing xenografts show increased thermogenic gene expression (UCP1, PGC1 alpha, ECH1, Cox8b, Dio2, Cyc1, PGC1 beta, PPAR alpha, Elvol3) in brown adipose tissue (BAT) and increased expression of lipolytic genes (Adrb3, ATGL, HSL) in both white adipose tissue (WAT) and BAT, consistent with higher energy metabolism. CONCLUSION: hNAG-1 modulates metabolic activity by increasing the expression of key thermogenic and lipolytic genes in BAT and WAT. hNAG-1 appears to be a novel therapeutic target in preventing and treating obesity and insulin resistance. C1 [Chrysovergis, K.; Wang, X.; Kosak, J.; Kim, J. S.; Singh, S.; Eling, T. E.] NIEHS, Mol Carcinogenesis Lab, NIH, Res Triangle Pk, NC 27709 USA. [Lee, S-H; Baek, S. J.] Univ Tennessee, Coll Vet Med, Dept Biomed & Diagnost Sci, Knoxville, TN USA. [Foley, J. F.; Travlos, G.] NIEHS, Cellular & Mol Pathol Branch, NIH, Res Triangle Pk, NC 27709 USA. [Kim, J. S.] Andong Natl Univ, Dept Biol Sci, Andong, South Korea. RP Eling, TE (reprint author), NIEHS, Mol Carcinogenesis Lab, NIH, 111 TW Alexander Dr,Bldg 101,Room D448B, Res Triangle Pk, NC 27709 USA. EM eling@niehs.nih.gov FU NIH, NIEHS Intramural Research Program [Z01- ES010016-14]; Center of Excellence in Livestock Diseases and Human Health, University of Tennessee FX We thank David Goulding, Page Myers and the Necropsy core for their technical help. We thank Drs Paul Wade and Xiaoling Li for critical reading of this manuscript. There are no conflicts of interests. This research was supported by NIH, NIEHS Intramural Research Program (Eling) Z01- ES010016-14 and in part, the Center of Excellence in Livestock Diseases and Human Health, University of Tennessee (Baek). NR 50 TC 12 Z9 12 U1 0 U2 8 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0307-0565 EI 1476-5497 J9 INT J OBESITY JI Int. J. Obes. PD DEC PY 2014 VL 38 IS 12 BP 1555 EP 1564 DI 10.1038/ijo.2014.27 PG 10 WC Endocrinology & Metabolism; Nutrition & Dietetics SC Endocrinology & Metabolism; Nutrition & Dietetics GA AX7PL UT WOS:000347107400011 PM 24531647 ER PT J AU Weiss, DJ Atkinson, PM Bhatt, S Mappin, B Hay, SI Gething, PW AF Weiss, Daniel J. Atkinson, Peter M. Bhatt, Samir Mappin, Bonnie Hay, Simon I. Gething, Peter W. TI An effective approach for gap-filling continental scale remotely sensed time-series SO ISPRS JOURNAL OF PHOTOGRAMMETRY AND REMOTE SENSING LA English DT Article DE Gap-filling; MODIS; EVI; LST; Africa ID SLC-OFF IMAGES; GEOSTATISTICAL APPROACH; CLOUDED PIXELS; MODIS; PRODUCTS; INTERPOLATION; COVER; VALIDATION AB The archives of imagery and modeled data products derived from remote sensing programs with high temporal resolution provide powerful resources for characterizing inter- and intra-annual environmental dynamics. The impressive depth of available time-series from such missions (e.g., MODIS and AVHRR) affords new opportunities for improving data usability by leveraging spatial and temporal information inherent to longitudinal geospatial datasets. In this research we develop an approach for filling gaps in imagery time-series that result primarily from cloud cover, which is particularly problematic in forested equatorial regions. Our approach consists of two, complementary gap-filling algorithms and a variety of run-time options that allow users to balance competing demands of model accuracy and processing time. We applied the gap-filling methodology to MODIS Enhanced Vegetation Index (EVI) and daytime and nighttime Land Surface Temperature (LST) datasets for the African continent for 2000-2012, with a 1 km spatial resolution, and an 8-day temporal resolution. We validated the method by introducing and filling artificial gaps, and then comparing the original data with model predictions. Our approach achieved R-2 values above 0.87 even for pixels within 500 km wide introduced gaps. Furthermore, the structure of our approach allows estimation of the error associated with each gap-filled pixel based on the distance to the non-gap pixels used to model its fill value, thus providing a mechanism for including uncertainty associated with the gap-filling process in downstream applications of the resulting datasets. (C) 2014 The Authors. Published by Elsevier B.V. on behalf of International Society for Photogrammetry and Remote Sensing, Inc. (ISPRS). C1 [Weiss, Daniel J.; Bhatt, Samir; Mappin, Bonnie; Hay, Simon I.; Gething, Peter W.] Univ Oxford, Dept Zool, Spatial Ecol & Epidemiol Grp, Oxford, England. [Atkinson, Peter M.] Univ Southampton, Southampton SO17 1BJ, Hants, England. [Hay, Simon I.] NIH, Fogarty Int Ctr, Bethesda, MD 20892 USA. RP Weiss, DJ (reprint author), Univ Oxford, Dept Zool, Spatial Ecol & Epidemiol Grp, Tinbergen Bldg, Oxford, England. EM daniel.weiss@zoo.ox.ac.uk RI Hay, Simon/F-8967-2015; OI Hay, Simon/0000-0002-0611-7272; Mappin, Bonnie/0000-0002-1205-719X; Gething, Peter/0000-0001-6759-5449 FU UK Medical Research Council (MRC) [K00669X]; UK Department for International Development (DFID) under the MRC/DFID [K00669X]; Bill and Melinda Gates Foundation [OPP1068048] FX PWG is a Career Development Fellow (#K00669X) jointly funded by the UK Medical Research Council (MRC) and the UK Department for International Development (DFID) under the MRC/DFID Concordat agreement and also receives support from the Bill and Melinda Gates Foundation (#OPP1068048). These grants also support DW, SB, and BM. NR 28 TC 19 Z9 19 U1 3 U2 13 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0924-2716 EI 1872-8235 J9 ISPRS J PHOTOGRAMM JI ISPRS-J. Photogramm. Remote Sens. PD DEC PY 2014 VL 98 BP 106 EP 118 DI 10.1016/j.isprsjprs.2014.10.001 PG 13 WC Geography, Physical; Geosciences, Multidisciplinary; Remote Sensing; Imaging Science & Photographic Technology SC Physical Geography; Geology; Remote Sensing; Imaging Science & Photographic Technology GA AX8BL UT WOS:000347135500009 PM 25642100 ER PT J AU Cimino, JJ Ayres, EJ Remennik, L Rath, S Freedman, R Beri, A Chen, Y Huser, V AF Cimino, James J. Ayres, Elaine J. Remennik, Lyubov Rath, Sachi Freedman, Robert Beri, Andrea Chen, Yang Huser, Vojtech TI The National Institutes of Health's Biomedical Translational Research Information System (BTRIS): Design, contents, functionality and experience to date SO JOURNAL OF BIOMEDICAL INFORMATICS LA English DT Article DE Clinical research; Translational research; Research data repository; Research data warehouse; Ontology ID DATABASE; TERMINOLOGIES; DESIDERATA; KNOWLEDGE; SCIENCE; MODEL; WEB AB The US National Institutes of Health (NIH) has developed the Biomedical Translational Research Information System (BTRIS) to support researchers' access to translational and clinical data. BTRIS includes a data repository, a set of programs for loading data from NIH electronic health records and research data management systems, an ontology for coding the disparate data with a single terminology, and a set of user interface tools that provide access to identified data from individual research studies and data across all studies from which individually identifiable data have been removed. This paper reports on unique design elements of the system, progress to date and user experience after five years of development and operation. Published by Elsevier Inc. C1 [Cimino, James J.; Ayres, Elaine J.; Remennik, Lyubov; Huser, Vojtech] NIH, Lab Informat Dev, Ctr Clin, Bethesda, MD 20892 USA. [Rath, Sachi; Freedman, Robert; Beri, Andrea; Chen, Yang] Comp Sci Corp, Falls Church, VA USA. RP Cimino, JJ (reprint author), NIH, Lab Informat Dev, Ctr Clin, Room 6-2551,10 Ctr Dr, Bethesda, MD 20892 USA. EM ciminoj@mail.nih.gov OI Cimino, James/0000-0003-4101-1622 FU NIH Clinical Center; National Library of Medicine FX The authors thank NIH Clinical Center Director John Gallin and former NIH Director Elias Zerhouni for the vision to launch the BTRIS project. We have had additional invaluable guidance from Dr. Richard Cannon and Dr. Richard Davey on many design and policy decisions. We also thank all the BTRIS staff, past and present, for their contributions to the project, especially Mark Budd, James Rohrbaugh and Donald Griffin. We are grateful to the National Cancer Institute's Center for Biomedical Informatics and Information Technology (CBIIT) for sharing their ontology development tools and experience. Drs. Cimino and Huser are supported by research funding from the NIH Clinical Center and the National Library of Medicine. NR 41 TC 3 Z9 3 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 1532-0464 EI 1532-0480 J9 J BIOMED INFORM JI J. Biomed. Inform. PD DEC PY 2014 VL 52 BP 11 EP 27 DI 10.1016/j.jbi.2013.11.004 PG 17 WC Computer Science, Interdisciplinary Applications; Medical Informatics SC Computer Science; Medical Informatics GA AY0HC UT WOS:000347277000003 PM 24262893 ER PT J AU Shang, N Xu, H Rindflesch, TC Cohen, T AF Shang, Ning Xu, Hua Rindflesch, Thomas C. Cohen, Trevor TI Identifying plausible adverse drug reactions using knowledge extracted from the literature SO JOURNAL OF BIOMEDICAL INFORMATICS LA English DT Article DE Pharmacovigilance; Distributional semantics; Literature-based discovery; Predication-based semantic indexing; Reflective random indexing ID LITERATURE-BASED DISCOVERY; ACTIVATED RECEPTOR-GAMMA; SPONTANEOUS REPORTING SYSTEM; ELECTRONIC HEALTH RECORDS; TYPE-2 DIABETES-MELLITUS; MIGRAINE-MAGNESIUM DISCOVERIES; UNDISCOVERED PUBLIC KNOWLEDGE; MYOCARDIAL-INFARCTION; PPAR-GAMMA; CARDIOVASCULAR OUTCOMES AB Pharmacovigilance involves continually monitoring drug safety after drugs are put to market. To aid this process; algorithms for the identification of strongly correlated drug/adverse drug reaction (ADR) pairs from data sources such as adverse event reporting systems or Electronic Health Records have been developed. These methods are generally statistical in nature, and do not draw upon the large volumes of knowledge embedded in the biomedical literature. In this paper, we investigate the ability of scalable Literature Based Discovery (LBD) methods to identify side effects of pharmaceutical agents. The advantage of LBD methods is that they can provide evidence from the literature to support the plausibility of a drug/ADR association, thereby assisting human review to validate the signal, which is an essential component of pharmacovigilance. To do so, we draw upon vast repositories of knowledge that has been extracted from the biomedical literature by two Natural Language Processing tools, MetaMap and SemRep. We evaluate two LBD methods that scale comfortably to the volume of knowledge available in these repositories. Specifically, we evaluate Reflective Random Indexing (RAI), a model based on concept-level co-occurrence, and Predication-based Semantic Indexing (PSI), a model that encodes the nature of the relationship between concepts to support reasoning analogically about drug-effect relationships. An evaluation set was constructed from the Side Effect Resource 2 (SIDER2), which contains known drug/ADR relations, and models were evaluated for their ability to "rediscover" these relations. In this paper, we demonstrate that both RRI and PSI can recover known drug-adverse event associations. However, PSI performed better overall, and has the additional advantage of being able to recover the literature underlying the reasoning pathways it used to make its predictions. (C) 2014 Elsevier Inc. All rights reserved. C1 [Shang, Ning; Xu, Hua; Cohen, Trevor] Univ Texas Hlth Sci Ctr Houston, Sch Biomed Informat, Houston, TX 77030 USA. [Rindflesch, Thomas C.] Natl Lib Med, Bethesda, MD USA. RP Shang, N (reprint author), Univ Texas Hlth Sci Ctr Houston, Sch Biomed Informat, Houston, TX 77030 USA. EM sunnyshang001@gmail.com FU U.S. National Library of Medicine [1R01LM011563]; Intramural Research Program of the U.S. National Institutes of Health, National Library of Medicine FX The work was supported by the U.S. National Library of Medicine Grant (1R01LM011563), Using Biomedical Knowledge to Identify Plausible Signals for Pharmacovigilance. This work was also supported in part by the Intramural Research Program of the U.S. National Institutes of Health, National Library of Medicine. The authors would like to thank Peter Davies for his comments on the paper, and for discussions regarding the implications of these methods for the evaluation of potential ADRs. NR 155 TC 9 Z9 9 U1 2 U2 13 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1532-0464 EI 1532-0480 J9 J BIOMED INFORM JI J. Biomed. Inform. PD DEC PY 2014 VL 52 BP 293 EP 310 DI 10.1016/j.jbi.2014.07.011 PG 18 WC Computer Science, Interdisciplinary Applications; Medical Informatics SC Computer Science; Medical Informatics GA AY0HC UT WOS:000347277000031 PM 25046831 ER PT J AU Mishra, R Bian, JT Fiszman, M Weir, CR Jonnalagadda, S Mostafa, J Del Fiol, G AF Mishra, Rashmi Bian, Jiantao Fiszman, Marcelo Weir, Charlene R. Jonnalagadda, Siddhartha Mostafa, Javed Del Fiol, Guilherme TI Text summarization in the biomedical domain: A systematic review of recent research SO JOURNAL OF BIOMEDICAL INFORMATICS LA English DT Review DE Text summarization; Intrinsic evaluation; Language processing; Machine learning; Biomedical domain ID KNOWLEDGE; STRATEGIES; DOCUMENTS AB Objective: The amount of information for clinicians and clinical researchers is growing exponentially. Text summarization reduces information as an attempt to enable users to find and understand relevant source texts more quickly and effortlessly. In recent years, substantial research has been conducted to develop and evaluate various summarization techniques in the biomedical domain. The goal of this study was to systematically review recent published research on summarization of textual documents in the biomedical domain. Materials and methods: MEDLINE (2000 to October 2013), IEEE Digital Library, and the ACM digital library were searched. Investigators independently screened and abstracted studies that examined text summarization techniques in the biomedical domain. Information is derived from selected articles on five dimensions: input, purpose, output, method and evaluation. Results: Of 10,786 studies retrieved, 34(0.3%) met the inclusion criteria. Natural language processing (17; 50%) and a hybrid technique comprising of statistical, Natural language processing and machine learning (15; 44%) were the most common summarization approaches. Most studies (28; 82%) conducted an intrinsic evaluation. Discussion: This is the first systematic review of text summarization in the biomedical domain. The study identified research gaps and provides recommendations for guiding future research on biomedical text summarization. Conclusion: Recent research has focused on a hybrid technique comprising statistical, language processing and machine learning techniques. Further research is needed on the application and evaluation of text summarization in real research or patient care settings. (C) 2014 Elsevier Inc. All rights reserved. C1 [Mishra, Rashmi; Bian, Jiantao; Weir, Charlene R.; Del Fiol, Guilherme] Univ Utah, Dept Biomed Informat, Salt Lake City, UT 84108 USA. [Bian, Jiantao] Intermt Healthcare, Clin Modeling Team, Salt Lake City, UT USA. [Fiszman, Marcelo] Natl Lib Med, Lister Hill Ctr, Bethesda, MD USA. [Weir, Charlene R.] VA Med Ctr, Salt Lake City, UT USA. [Jonnalagadda, Siddhartha] Northwestern Univ, Dept Prevent Med Hlth & Biomed Informat, Chicago, IL 60611 USA. [Mostafa, Javed] Univ N Carolina, SILS, Chapel Hill, NC USA. RP Del Fiol, G (reprint author), Univ Utah, Dept Biomed Informat, 421 Wakara Way, Salt Lake City, UT 84108 USA. EM guilherme.delfiol@utah.edu OI Bian, Jiantao/0000-0001-5989-5177; Del Fiol, Guilherme/0000-0001-9954-6799 FU National Library of Medicine [1R01LM011416] FX The authors would like to acknowledge Alice Weber for providing insights on the search strategy of this systematic review. This project was supported by Grant Number 1R01LM011416-01 from the National Library of Medicine. NR 52 TC 4 Z9 4 U1 0 U2 15 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1532-0464 EI 1532-0480 J9 J BIOMED INFORM JI J. Biomed. Inform. PD DEC PY 2014 VL 52 BP 457 EP 467 DI 10.1016/j.jbi.2014.06.009 PG 11 WC Computer Science, Interdisciplinary Applications; Medical Informatics SC Computer Science; Medical Informatics GA AY0HC UT WOS:000347277000046 PM 25016293 ER PT J AU Kuban, KCK O'Shea, TM Allred, EN Paneth, N Hirtz, D Fichorova, RN Leviton, A AF Kuban, Karl C. K. O'Shea, T. Michael Allred, Elizabeth N. Paneth, Nigel Hirtz, Deborah Fichorova, Raina N. Leviton, Alan CA ELGAN Study Investigators TI Systemic Inflammation and Cerebral Palsy Risk in Extremely Preterm Infants SO JOURNAL OF CHILD NEUROLOGY LA English DT Article DE cerebral palsy risk; inflammation ID WHITE-MATTER DAMAGE; LOW GESTATIONAL-AGE; BRAIN-DAMAGE; PERIVENTRICULAR LEUKOMALACIA; HISTOLOGIC CHARACTERISTICS; CHILDREN BORN; 28TH WEEK; BLOOD; CYTOKINES; PROTEINS AB The authors hypothesized that among extremely preterm infants, elevated concentrations of inflammation-related proteins in neonatal blood are associated with cerebral palsy at 24 months. In 939 infants born before 28 weeks gestation, the authors measured blood concentrations of 25 proteins on postnatal days 1, 7, and 14 and evaluated associations between elevated protein concentrations and cerebral palsy diagnosis. Protein elevations within 3 days of birth were not associated with cerebral palsy. Elevations of tumor necrosis factor-alpha, tumor necrosis factor-alpha-receptor-1, interleukin-8, and intercellular adhesion molecule-1 on at least 2 days were associated with diparesis. Recurrent-persistent elevations of interleukin-6, E-selectin, or insulin-like growth factor binding protein-1 were associated with hemiparesis. Diparesis and hemiparesis were more likely among infants who had at least 4 of 9 protein elevations that previously have been associated with cognitive impairment and microcephaly. Repeated elevations of inflammation-related proteins during the first 2 postnatal weeks are associated with increased risk of cerebral palsy. C1 [Kuban, Karl C. K.] Boston Med Ctr, Dept Pediat, Boston, MA USA. [O'Shea, T. Michael] Wake Forest Univ, Bowman Gray Sch Med, Winston Salem, NC USA. [Allred, Elizabeth N.; Fichorova, Raina N.; Leviton, Alan] Harvard Univ, Sch Med, Boston, MA USA. [Allred, Elizabeth N.; Leviton, Alan] Boston Childrens Hosp, Boston, MA USA. [Allred, Elizabeth N.] Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA. [Paneth, Nigel] Michigan State Univ, Dept Epidemiol & Biostat, E Lansing, MI 48824 USA. [Hirtz, Deborah] NINDS, Bethesda, MD 20892 USA. [Fichorova, Raina N.] Brigham & Womens Hosp, Dept Obstet Gynecol & Reprod Biol, Boston, MA 02115 USA. RP Kuban, KCK (reprint author), Boston Univ, Sch Med, Boston Med Ctr, Dept Pediat, 771 Albany St, Boston, MA 02118 USA. EM karl.kuban@bmc.org FU National Institute of Neurological Disorders and Stroke [5U01NS040069-05, 2R01NS040069-06A2] FX The authors disclosed receipt of the following financial support for the research, authorship, and/or publication of this article: This study was completed as a cooperative agreement with the National Institute of Neurological Disorders and Stroke (5U01NS040069-05 and 2R01NS040069-06A2). The study sponsor participated in the study design, analyses, and manuscript writing. NR 49 TC 12 Z9 12 U1 0 U2 4 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 0883-0738 EI 1708-8283 J9 J CHILD NEUROL JI J. Child Neurol. PD DEC PY 2014 VL 29 IS 12 BP 1692 EP 1698 DI 10.1177/0883073813513335 PG 7 WC Clinical Neurology; Pediatrics SC Neurosciences & Neurology; Pediatrics GA AX4NB UT WOS:000346908000024 PM 24646503 ER PT J AU Goswami, SC Mishra, SK Maric, D Kaszas, K Gonnella, GL Clokie, SJ Kominsky, HD Gross, JR Keller, JM Mannes, AJ Hoon, MA Iadarola, MJ AF Goswami, Samridhi C. Mishra, Santosh K. Maric, Dragan Kaszas, Krisztian Gonnella, Gian Luigi Clokie, Samuel J. Kominsky, Hal D. Gross, Jacklyn R. Keller, Jason M. Mannes, Andrew J. Hoon, Mark A. Iadarola, Michael J. TI Molecular Signatures of Mouse TRPV1-Lineage Neurons Revealed by RNA-Seq Transcriptome Analysis SO JOURNAL OF PAIN LA English DT Article DE Pain; nociception; dorsal root ganglion; capsaicin; resiniferatoxin ID DORSAL-ROOT GANGLION; PRIMARY SENSORY NEURONS; PRIMARY AFFERENT NEURONS; MU-OPIOID RECEPTORS; SPINAL-CORD; NEUROPATHIC PAIN; GENE-EXPRESSION; THERMAL STIMULI; C-KIT; DIFFERENTIAL EXPRESSION AB Disorders of pain neural systems are frequently chronic and, when recalcitrant to treatment, can severely degrade the quality of life. The pain pathway begins with sensory neurons in dorsal root or trigeminal ganglia, and the neuronal subpopulations that express the transient receptor potential cation channel, subfamily V. member 1 (TRPV1) ion channel transduce sensations of painful heat and inflammation and play a fundamental role in clinical pain arising from cancer and arthritis. In the present study, we elucidate the complete transcriptomes of neurons from the TRPV1 lineage and a non-TRPV1 neuroglial population in sensory ganglia through the combined application of next-gen deep RNA-Seq, genetic neuronal labeling with fluorescence-activated cell sorting, or neuron-selective chemoablation. RNA-Seq accurately quantitates gene expression, a difficult parameter to determine with most other methods, especially for very low and very high expressed genes. Differentially expressed genes are present at every level of cellular function from the nucleus to the plasma membrane. We identified many ligand receptor pairs in the TRPV1 population, suggesting that autonomous presynaptic regulation may be a major regulatory mechanism in nociceptive neurons. The data define, in a quantitative, cell population-specific fashion, the molecular signature of a distinct and clinically important group of pain-sensing neurons and provide an overall framework for understanding the transcriptome of TRPV1 nociceptive neurons. Perspective: Next-gen RNA-Seq, combined with molecular genetics, provides a comprehensive and quantitative measurement of transcripts in TRPV1 lineage neurons and a contrasting transcriptome from non-TRPV1 neurons and cells. The transcriptome highlights previously unrecognized protein families, identifies multiple molecular circuits for excitatory or inhibitory autocrine and paracrine signaling, and suggests new combinatorial approaches to pain control. Published by Elsevier Inc. C1 [Goswami, Samridhi C.; Kaszas, Krisztian; Gonnella, Gian Luigi; Clokie, Samuel J.; Kominsky, Hal D.; Gross, Jacklyn R.; Keller, Jason M.; Mannes, Andrew J.; Iadarola, Michael J.] NIH, Ctr Clin, Dept Perioperat Med, Anesthesia Sect, Bethesda, MD 20892 USA. [Mishra, Santosh K.; Hoon, Mark A.] Natl Inst Dent & Craniofacial Res, Lab Sensory Biol, Mol Genet Unit, Bethesda, MD USA. [Maric, Dragan] NINDS, Neurophysiol Lab, NIH, Bethesda, MD 20892 USA. RP Iadarola, MJ (reprint author), NIH, Ctr Clin, Dept Perioperat Med, Bldg 10,Room 2C401,10 Ctr Dr,MSC 1510, Bethesda, MD 20892 USA. EM michael.iadarola@nih.gov OI Clokie, Samuel/0000-0002-0025-3652 FU National Center for Complementary and Alternative Medicine; National Institute of Dental and Craniofacial Research; Department of Perioperative Medicine, Clinical Center of the National Institutes of Health FX This research was supported by the Intramural Research Programs of the National Center for Complementary and Alternative Medicine, the National Institute of Dental and Craniofacial Research, and the Department of Perioperative Medicine, Clinical Center of the National Institutes of Health. Supplementary data accompanying this article are available online at www.jpain.org and www.sciencedirect.com. NR 107 TC 15 Z9 15 U1 0 U2 8 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 DEC PY 2014 VL 15 IS 12 BP 1338 EP 1359 DI 10.1016/j.jpain.2014.09.010 PG 22 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA AX4HC UT WOS:000346893100013 PM 25281809 ER PT J AU Hanson, LC Bull, J Wessell, K Massie, L Bennett, RE Kutner, JS Aziz, NM Abernethy, A AF Hanson, Laura C. Bull, Janet Wessell, Kathryn Massie, Lisa Bennett, Rachael E. Kutner, Jean S. Aziz, Noreen M. Abernethy, Amy TI Strategies to Support Recruitment of Patients With Life-Limiting Illness for Research: The Palliative Care Research Cooperative Group SO JOURNAL OF PAIN AND SYMPTOM MANAGEMENT LA English DT Article DE Palliative care; recruitment; research networks; clinical trials ID STATIN THERAPY; EVIDENCE BASE; DISCONTINUATION; METAANALYSIS; MEDICATIONS; CHALLENGES; PATTERNS AB Context. The Palliative Care Research Cooperative Group (PCRC) is the first clinical trials cooperative for palliative care in the U.S. Objectives. To describe barriers and strategies for recruitment during the inaugural PCRC clinical trial. Methods. The parent study was a multisite randomized controlled trial enrolling adults with life expectancy anticipated to be one to six months, randomized to discontinue statins (intervention) vs. to continue on statins (control). To study recruitment best practices, we conducted semistructured interviews with 18 site principal investigators (PIs) and clinical research coordinators (CRCs) and reviewed recruitment rates. Interviews covered three topics: 1) successful strategies for recruitment, 2) barriers to recruitment, and 3) optimal roles of the PI and CRC. Results. All eligible site PIs and CRCs completed interviews and provided data on statin protocol recruitment. The parent study completed recruitment of 381 patients. Site enrollment ranged from 1 to 109 participants, with an average of 25 enrolled per site. Five major barriers included difficulty locating eligible patients, severity of illness, family and provider protectiveness, seeking patients in multiple settings, and lack of resources for recruitment activities. Five effective recruitment strategies included systematic screening of patient lists, thoughtful messaging to make research relevant, flexible protocols to accommodate patients' needs, support from clinical champions, and the additional resources of a trials cooperative group. Conclusion. The recruitment experience from the multisite PCRC yields new insights into methods for effective recruitment to palliative care clinical trials. These results will inform training materials for the PCRC and may assist other investigators in the field. J Pain Symptom Manage 2014;48:1021-1030. (C) 2014 American Academy of Hospice and Palliative Medicine. Published by Elsevier Inc. All rights reserved. C1 [Hanson, Laura C.] Univ N Carolina, Div Geriatr Med, Chapel Hill, NC 27599 USA. [Hanson, Laura C.] Univ N Carolina, Palliat Care Program, Chapel Hill, NC 27599 USA. [Hanson, Laura C.; Wessell, Kathryn] Univ N Carolina, Cecil B Sheps Ctr Hlth Serv Res, Chapel Hill, NC 27599 USA. [Bull, Janet; Massie, Lisa] Four Seasons Hosp & Palliat Care, Flat Rock, NC USA. [Bennett, Rachael E.; Kutner, Jean S.] Univ Colorado, Sch Med, Dept Med, Div Gen Internal Med, Denver, CO USA. [Aziz, Noreen M.] NINR, NIH, Bethesda, MD 20892 USA. [Abernethy, Amy] Duke Univ, Sch Med, Dept Med, Div Oncol, Durham, NC 27706 USA. RP Hanson, LC (reprint author), Univ N Carolina, Div Geriatr Med, CB 7550, Chapel Hill, NC 27599 USA. EM lhanson@med.unc.edu OI Wessell, Kathryn/0000-0001-9127-7088 FU National Institutes of Health-National Institute of Nursing Research [UC4 NR012584]; National Institute of Nursing Research; National Institute on Aging; National Heart, Lung, and Blood Institute; National Cancer Institute; Agency for Healthcare Research and Quality; DARA; GlaxoSmithKline; Celgene; Helsinn; Dendreon; Pfizer; Informed Medical Decisions Foundation FX This study was supported by National Institutes of Health-National Institute of Nursing Research grant UC4 NR012584. Dr. Hanson has research funding from the National Institute of Nursing Research, the National Institute on Aging, and the National Heart, Lung, and Blood Institute. Funds are distributed to the University of North Carolina for salary and research support. Further consulting is pending for the Research Triangle Institute. Dr. Abernethy has research funding from the National Institute of Nursing Research, National Cancer Institute, Agency for Healthcare Research and Quality, DARA, GlaxoSmithKline, Celgene, Helsinn, Dendreon, and Pfizer; these funds are all distributed to Duke University Medical Center to support research including salary support for Dr. Abernethy. Pending industry-funded projects include Genentech, Bristol-Myers Squibb, Insys, and Kanglaite. In the last two years, she has had nominal consulting agreements with or received honoraria (<$10,000 annually) from Novartis, Bristol-Myers Squibb, and Pfizer. Consulting with Bristol-Meyers Squibb in 2013, for role as cochair of a Scientific Advisory Committee. Dr. Abernethy had a paid leadership role with American Academy of Hospice & Palliative Medicine (President). She has corporate leadership responsibility in AthenaHealth (health IT company), Advoset (an education company that has a contract with Novartis), and Orange Leaf Associates LLC (an IT development company). Dr. Kutner has research funding from the National Institute of Nursing Research, National Cancer Institute, and Agency for Healthcare Research and Quality. She is supported by the Informed Medical Decisions Foundation in her role as medical editor. All these funds are distributed to University of Colorado School of Medicine to support research including salary support for Dr. Kutner. NR 30 TC 2 Z9 2 U1 0 U2 9 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0885-3924 EI 1873-6513 J9 J PAIN SYMPTOM MANAG JI J. Pain Symptom Manage. PD DEC PY 2014 VL 48 IS 6 BP 1021 EP 1030 DI 10.1016/j.jpainsymman.2014.04.008 PG 10 WC Health Care Sciences & Services; Medicine, General & Internal; Clinical Neurology SC Health Care Sciences & Services; General & Internal Medicine; Neurosciences & Neurology GA AX1ZG UT WOS:000346742300001 PM 24863152 ER PT J AU Hsiao, CP Wang, D Kaushal, A Chen, MK Saligan, L AF Hsiao, Chao-Pin Wang, Dan Kaushal, Aradhana Chen, Mei-Kuang Saligan, Leorey TI Differential Expression of Genes Related to Mitochondrial Biogenesis and Bioenergetics in Fatigued Prostate Cancer Men Receiving External Beam Radiation Therapy SO JOURNAL OF PAIN AND SYMPTOM MANAGEMENT LA English DT Article DE Fatigue; gene expression; mitochondria; biogenesis; bioenergetics; prostate cancer; radiation therapy ID ALPHA-SYNUCLEIN; RADIOTHERAPY; AUTOPHAGY; PATIENT; HOMEOSTASIS; ACTIVATION; DEPRESSION; MITOPHAGY; MUTATION; FISSION AB Objectives. This prospective study explored relationships between expression changes of genes related to mitochondrial biogenesis/bioenergetics and fatigue in men with prostate cancer receiving external beam radiation therapy (EBRT). Methods. Fatigue and gene expression were measured before (Day 0), at midpoint (Days 19-21), and at completion (Days 38-42) of EBRT using the seven-item Patient-Reported Outcomes Measurement Information System-Fatigue short form and from whole blood cell RNA, respectively. The human mitochondria RT2 Profiler (TM) PCR Array System was used to identify differential expression of mitochondrial biogenesis/bioenergetics-related genes. Mixed linear modeling estimated the changes in fatigue and gene expression over time and determined significant associations between gene expression and fatigue. Results. Subjects were 50 men with prostate cancer (scheduled for EBRT = 25, active surveillance as matched controls = 25). The mean Patient-Reported Outcomes Measurement Information System-Fatigue T-score (mean = 50 +/- 10 in a general population) for study subjects was 44.87 +/- 5.89 and for controls was 43.5 +/- 2.8 at baseline. Differential expression of two genes inside the mitochondria involved in critical mitochondrial complexes: BCS1L (beta = 1.30), SLC25A37 (beta = -2.44), and two genes on the outer mitochondrial membrane vital for mitochondrial integrity: BCL2L1 (beta = -1.68) and FIS1 (beta = -2.35) were significantly associated with changes in fatigue scores of study subjects during EBRT. Conclusion. Genes related to oxidative phosphorylation, energy production, and mitochondrial membrane integrity are associated with worsening fatigue during EBRT. Further investigation of the pathways involved with this association may explain mechanisms behind the development of fatigue in this population. Published by Elsevier Inc. on behalf of American Academy of Hospice and Palliative Medicine. C1 [Hsiao, Chao-Pin; Wang, Dan; Saligan, Leorey] NINR, NIH, Cleveland, OH 44106 USA. [Kaushal, Aradhana] NCI, NIH, Cleveland, OH USA. [Chen, Mei-Kuang] Univ Arizona, Tucson, AZ USA. [Hsiao, Chao-Pin] Case Western Reserve Univ, Cleveland, OH 44106 USA. RP Hsiao, CP (reprint author), NINR, 2120 Cornell Rd, Cleveland, OH 44106 USA. EM cxh416@case.edu OI Chen, Mei-kuang/0000-0002-0407-6788 FU Intramural Research Program of National Institute of Nursing Research, National Institutes of Health, Bethesda, MD [09-NR-0088] FX This study was supported by the Intramural Research Program of National Institute of Nursing Research (Protocol # 09-NR-0088), National Institutes of Health, Bethesda, MD. The authors have no consultant or advisory positions and no stock or other ownership interests to disclose. NR 41 TC 4 Z9 4 U1 1 U2 3 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0885-3924 EI 1873-6513 J9 J PAIN SYMPTOM MANAG JI J. Pain Symptom Manage. PD DEC PY 2014 VL 48 IS 6 BP 1080 EP 1090 DI 10.1016/j.jpainsymman.2014.03.010 PG 11 WC Health Care Sciences & Services; Medicine, General & Internal; Clinical Neurology SC Health Care Sciences & Services; General & Internal Medicine; Neurosciences & Neurology GA AX1ZG UT WOS:000346742300007 PM 24786901 ER PT J AU Abernethy, AP Capell, WH Aziz, NM Ritchie, C Prince-Paul, M Bennett, RE Kutner, JS AF Abernethy, Amy P. Capell, Warren H. Aziz, Noreen M. Ritchie, Christine Prince-Paul, Maryjo Bennett, Rachael E. Kutner, Jean S. TI Ethical Conduct of Palliative Care Research: Enhancing Communication Between Investigators and Institutional Review Boards SO JOURNAL OF PAIN AND SYMPTOM MANAGEMENT LA English DT Article DE Palliative care; human subjects protection; research ethics; institutional review boards ID END-OF-LIFE; CLINICAL-RESEARCH; EVIDENCE BASE; ISSUES; CHALLENGES; STRATEGIES; GUIDELINES; BARRIERS; SCIENCE; CANCER AB Palliative care has faced moral and ethical challenges when conducting research involving human subjects. There are currently no resources to guide institutional review boards (IRBs) in applying standard ethical principles and terms-in a specific way-to palliative care research. Using as a case study a recently completed multisite palliative care clinical trial, this article provides guidance and recommendations for both IRBs and palliative care investigators to facilitate communication and attain the goal of conducting ethical palliative care research and protecting study participants while advancing the science. Beyond identifying current challenges faced by palliative care researchers and IRBs reviewing palliative care research, this article suggests steps that the palliative care research community can take to establish a scientifically sound, stable, productive, and well-functioning relationship between palliative care investigators and the ethical bodies that oversee their work. (C) 2014 American Academy of Hospice and Palliative Medicine. Published by Elsevier Inc. All rights reserved. C1 [Abernethy, Amy P.] Duke Univ, Sch Med, Duke Clin Res Inst, Durham, NC USA. [Abernethy, Amy P.] Duke Univ, Sch Med, Duke Canc Inst, Durham, NC USA. [Capell, Warren H.; Bennett, Rachael E.] Univ Colorado, Sch Med, Aurora, CO USA. [Aziz, Noreen M.] NINR, Div Extramural Act, NIH, Bethesda, MD 20892 USA. [Ritchie, Christine] Univ Calif San Francisco, San Francisco, CA 94143 USA. [Prince-Paul, Maryjo] Case Western Reserve Univ, Frances Payne Bolton Sch Nursing, Cleveland, OH 44106 USA. RP Kutner, JS (reprint author), Univ Colorado, Sch Med, 12631 E 17th Ave,Mail Stop B180, Aurora, CO 80045 USA. EM Jean.Kutner@ucdenver.edu FU NINR [1UC4NR012584-01]; National Cancer Institute; Agency for Healthcare Research and Quality; DARA; GlaxoSmithKline; Celgene; Helsinn; Dendreon; Pfizer; National Institute on Aging; Commonwealth Fund; Retirement Research Foundation; California Healthcare Foundation; Steven D. Bechtel, Jr. Foundation; National Heart Lung Blood Institute; American Cancer Society FX This work was supported by the NINR (1UC4NR012584-01). Dr. Abernethy has research funding from the NINR, National Cancer Institute, Agency for Healthcare Research and Quality, DARA, GlaxoSmithKline, Celgene, Helsinn, Dendreon, and Pfizer; all these funds are distributed to Duke University Medical Center to support research including salary support for Dr. Abernethy. Pending industry-funded projects include Genentech, Bristol-Myers Squibb, Insys, and Kanglaite. In the last two years, she has had nominal consulting agreements with or received honoraria (<$10,000 annually) from Novartis, Bristol-Myers Squibb, and Pfizer. Dr. Abernethy had a paid leadership role with American Academy of Hospice & Palliative Medicine (President). She has corporate leadership responsibility in AthenaHealth (health IT company), Advoset (an education company that has a contract with Novartis), and Orange Leaf Associates LLC (an IT development company). Dr. Ritchie has research funding from the NINR, National Institute on Aging, the Commonwealth Fund, the Retirement Research Foundation, the California Healthcare Foundation, and the Steven D. Bechtel, Jr. Foundation. All these funds are distributed to the University of California San Francisco to support research including salary support for Dr. Ritchie. She is also Editor for Up to Date Palliative Care.; Dr. Kutner has research funding from the NINR, National Institute on Aging, National Cancer Institute, Agency for Healthcare Research and Quality, the National Heart Lung Blood Institute, and the American Cancer Society. Dr. Kutner is a Medical Editor for the Informed Medical Decisions Foundation. All these funds are distributed to the University of Colorado to support research including salary support for Dr. Kutner. Drs. Capell, Prince-Paul and Aziz and Ms. Bennett have no disclosures. NR 44 TC 0 Z9 1 U1 1 U2 9 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0885-3924 EI 1873-6513 J9 J PAIN SYMPTOM MANAG JI J. Pain Symptom Manage. PD DEC PY 2014 VL 48 IS 6 BP 1211 EP 1221 DI 10.1016/j.jpainsymman.2014.05.005 PG 11 WC Health Care Sciences & Services; Medicine, General & Internal; Clinical Neurology SC Health Care Sciences & Services; General & Internal Medicine; Neurosciences & Neurology GA AX1ZG UT WOS:000346742300019 PM 24879998 ER PT J AU Schmoll, HJ Twelves, C Sun, WJ O'Connell, MJ Cartwright, T McKenna, E Saif, M Lee, S Yothers, G Haller, D AF Schmoll, Hans-Joachim Twelves, Chris Sun, Weijing O'Connell, Michael J. Cartwright, Thomas McKenna, Edward Saif, Muhammad Lee, Steve Yothers, Greg Haller, Daniel TI Effect of adjuvant capecitabine or fluorouracil, with or without oxaliplatin, on survival outcomes in stage III colon cancer and the effect of oxaliplatin on post-relapse survival: a pooled analysis of individual patient data from four randomised controlled trials SO LANCET ONCOLOGY LA English DT Article ID METASTATIC COLORECTAL-CANCER; ACID PLUS OXALIPLATIN; PHASE-III; 5-FLUOROURACIL/FOLINIC ACID; 1ST-LINE THERAPY; MONTHLY REGIMEN; ONCOLOGY-GROUP; NSABP C-07; LEUCOVORIN; BEVACIZUMAB AB Background Oxaliplatin-based adjuvant therapy is the standard of care for stage III colon cancer. Adjuvant capecitabine with or without oxaliplatin versus leucovorin and fluorouracil with or without oxaliplatin has not been directly compared; therefore, we aimed to analyse the efficacy and safety of these treatments using individual patient data pooled from four randomised controlled trials. We also assessed post-relapse survival, which has been postulated to be worse in patients receiving adjuvant oxaliplatin. Methods Patients with resected stage III colon cancer who were 18 years of age or older, with an Eastern Cooperative Oncology Group performance status of 0 or 1, from four randomised controlled trials (NSABP C-08, XELOXA, X-ACT, and AVANT; 8734 patients in total) were pooled and analysed. The treatment regimens included in our analyses were: XELOX (oxaliplatin and capecitabine); leucovorin and fluorouracil; capecitabine; FOLFOX-4 (leucovorin, fluorouracil, and oxaliplatin); and modified FOLFOX-6 (mFOLFOX-6). Disease-free survival was the primary endpoint for all trials that supplied patients for this analysis. Here, we compared disease-free, relapse-free, and overall survival between the patient groups who received capecitabine with or without oxaliplatin and those who received leucovorin and fluorouracil with or without oxaliplatin. Post-relapse survival was compared between the combined XELOX and FOLFOX groups, and the leucovorin and fluorouracil groups. Post-relapse survival was also compared between the capecitabine with or without oxaliplatin and leucovorin and fluorouracil with or without oxaliplatin groups. Findings Disease-free survival did not differ significantly between patients who received leucovorin and fluorouracil versus those who received capecitabine in adjusted analyses (hazard ratio [HR] 1.02 [0.93-1.11; p=0.72]) or in unadjusted analyses (HR 1.01 [95% CI 0.92-1.10; p= 0.86]). Relapse-free survival was similar (adjusted HR 1.02 [0.93-1.12; p=0.72] and unadjusted HR 1.01 [95% CI 0.92-1.11; p=0.86]), as was overall survival (adjusted HR 1.04 [95% CI 0.93-1.15; p=0.50] and unadjusted HR 1.02 [0.92-1.14]; p=0.65). For overall survival, a significant interaction between oxaliplatin and fluoropyrimidine was recorded in the multiple Cox regression analysis (p=0.014). Post-relapse survival was similar in adjusted (p=0.23) and unadjusted analyses (p=0.33) for the comparison of XELOX or FOLFOX versus leucovorin and fluorouracil, and was also similar for capecitabine-based regimens versus leucovorin and fluorouracil-based regimens (unadjusted p=0.26). Interpretation Combination therapy with oxaliplatin provided consistently improved outcomes without adversely affecting post-relapse survival in the adjuvant treatment of stage III colon cancer, irrespective of whether the fluoropyrimidine backbone was capecitabine or leucovorin and fluorouracil. These data add to the existing evidence that oxaliplatin plus capecitabine or leucovorin and fluorouracil is the standard of care for the adjuvant treatment of stage III colon cancer, and offers physicians flexibility to treat patients according to the patients' overall physical performance and preference. C1 [Schmoll, Hans-Joachim] Univ Halle Wittenberg, Univ Clin, D-06120 Halle, Germany. [Twelves, Chris] Leeds Inst Canc & Pathol, Leeds, W Yorkshire, England. [Twelves, Chris] St James Univ Hosp, Leeds, W Yorkshire, England. [Sun, Weijing] Univ Pittsburgh, Inst Canc, Pittsburgh, PA USA. [O'Connell, Michael J.] Natl Surg Adjuvant Breast & Bowel Project NSABP, Pittsburgh, PA USA. [Cartwright, Thomas] Florida Canc Affiliates, New Port Richey, FL USA. [McKenna, Edward] Genentech Inc, San Francisco, CA 94080 USA. [Saif, Muhammad] Tufts Univ, Sch Med, Boston, MA 02111 USA. [Yothers, Greg] NSABP, Biostat Ctr, Pittsburgh, PA USA. [Yothers, Greg] Univ Pittsburgh, Grad Sch Publ Hlth, Dept Biostat, Pittsburgh, PA 15261 USA. [Haller, Daniel] Univ Penn, Abramson Canc Ctr, Philadelphia, PA 19104 USA. RP Schmoll, HJ (reprint author), Univ Halle Wittenberg, Univ Clin, Dept Internal Med, Ernst Grube Str 40, D-06120 Halle, Germany. EM hans-joachim.schmoll@uk-halle.de FU Genentech Inc. FX Genentech Inc. NR 30 TC 21 Z9 22 U1 0 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1470-2045 EI 1474-5488 J9 LANCET ONCOL JI Lancet Oncol. PD DEC PY 2014 VL 15 IS 13 BP 1481 EP 1492 DI 10.1016/S1470-2045(14)70486-3 PG 12 WC Oncology SC Oncology GA AX4OT UT WOS:000346912300047 PM 25456367 ER PT J AU Anic, GM Weinstein, SJ Mondul, AM Mannisto, S Albanes, D AF Anic, Gabriella M. Weinstein, Stephanie J. Mondul, Alison M. Mannisto, Satu Albanes, Demetrius TI Serum vitamin D, vitamin D binding protein, and lung cancer survival SO LUNG CANCER LA English DT Article DE Serum vitamin D; Vitamin D binding protein; Lung cancer; Survival; Cohort; 25-hydroxyvitamin D ID CIRCULATING 25-HYDROXYVITAMIN D; PHYSICAL-ACTIVITY; RISK; COHORT; REPRODUCIBILITY; POPULATION; PROGNOSIS; PLASMA; D-3; POLYMORPHISMS AB Objectives: Vitamin D may prolong cancer survival by inhibiting tumor progression and metastasis, however, there are limited epidemiologic studies regarding the association between circulating 25-hydroxyvitamin D (25(OH)D) and lung cancer survival. The aim of this study was to examine the relationship between serum 25(OH)D and lung cancer specific survival and to evaluate whether vitamin D binding protein (DBP) concentration modified this association. Materials and methods: 25(OH)D and DBP were measured in fasting serum samples from 500 male lung cancer cases in the Alpha-Tocopherol, Beta-Carotene Cancer Prevention Study. Cox proportional hazards regression was used to estimate hazard ratios (HRs) and 95% confidence intervals (CI) for lung cancer related death according to quartiles of season-specific 25(OH)D, DBP, and the molar ratio of 25(OH)D:DBP, a proxy for free circulating 25(OH)D. Results: Comparing highest to lowest quartiles, serum 25(OH)D (HR=1.18; 95% CI: 0.89-1.56) and DBP (HR=0.95; 95% CI: 0.71-1.26) were not associated with lung cancer survival and DBP concentration did not modify the association with 25(OH)D (p for interaction=0.56). There was suggestion of an association between higher serum 25(OH)D and better survival from adenocarcinoma (HR=0.64; 95% CI: 0.17-2.45) and small cell carcinoma (HR=0.55; 95% CI: 0.21-1.45), but these estimates were based on a relatively small number of cases. Conclusion: Serum 25(OH)D was not associated with overall lung cancer survival regardless of DBP concentration, however, these findings should be examined in other studies that include women and subjects with higher 25(OH)D levels. Published by Elsevier Ireland Ltd. C1 [Anic, Gabriella M.] NCI, Canc Prevent Fellowship Program, Canc Prevent Div, Bethesda, MD 20892 USA. [Anic, Gabriella M.; Weinstein, Stephanie J.; Mondul, Alison M.; Albanes, Demetrius] NCI, Nutr Epidemiol Branch, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. [Mannisto, Satu] Natl Inst Hlth & Welf, Dept Chron Dis Prevent, Helsinki, Finland. RP Anic, GM (reprint author), NCI, Nutr Epidemiol Branch, Div Canc Epidemiol & Genet, 9609 Med Ctr Dr,6E316, Bethesda, MD 20892 USA. EM gabriella.anic@nih.gov RI Albanes, Demetrius/B-9749-2015; OI Mondul, Alison/0000-0002-8843-1416; Mannisto, Satu/0000-0002-8668-3046 FU US National Institutes of Health; National Cancer Institute; US Public Health Service from the National Cancer Institute [N01-CN-45165, N01-RC-45035, N01-RC-37004, HHSN261201000006C] FX This work was supported in part by the Intramural Research Program of the US National Institutes of Health and the National Cancer Institute. Additionally, this research was supported by US Public Health Service contracts N01-CN-45165, N01-RC-45035, N01-RC-37004, and HHSN261201000006C from the National Cancer Institute. NR 42 TC 6 Z9 6 U1 0 U2 10 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0169-5002 EI 1872-8332 J9 LUNG CANCER JI Lung Cancer PD DEC PY 2014 VL 86 IS 3 BP 297 EP 303 DI 10.1016/j.lungcan.2014.10.008 PG 7 WC Oncology; Respiratory System SC Oncology; Respiratory System GA AX8BU UT WOS:000347136400001 PM 25456734 ER PT J AU Beerli, RR Bauer, M Fritzer, A Rosen, LB Buser, RB Hanner, M Maudrich, M Nebenfuehr, M Toepfer, JAS Mangold, S Bauer, A Holland, SM Browne, SK Meinke, A AF Beerli, Roger R. Bauer, Monika Fritzer, Andrea Rosen, Lindsey B. Buser, Regula B. Hanner, Markus Maudrich, Melanie Nebenfuehr, Mario Toepfer, Jorge Alejandro Sepulveda Mangold, Susanne Bauer, Anton Holland, Steven M. Browne, Sarah K. Meinke, Andreas TI Mining the human autoantibody repertoire: Isolation of potent IL17A-neutralizing monoclonal antibodies from a patient with thymoma SO MABS LA English DT Article DE AIN457; human autoantibodies; ixekizumab; IL17; mammalian cell display; monoclonal antibodies; secukinumab; Sindbis virus; scFv-Fc ID CHRONIC MUCOCUTANEOUS CANDIDIASIS; INFLUENZA-A VIRUSES; ANTI-CYTOKINE AUTOANTIBODIES; SEVERE PLAQUE PSORIASIS; GM-CSF AUTOANTIBODIES; CANCER-CELL GROWTH; RHEUMATOID-ARTHRITIS; NEUTRALIZING ANTIBODIES; DOUBLE-BLIND; MOLECULAR CHARACTERIZATION AB Anti-cytokine autoantibodies have been widely reported to be present in human plasma, both in healthy subjects and in patients with underlying autoimmune conditions, such as autoimmune polyendocrinopathy candidiasis ectodermal dystrophy (APECED) or thymic epithelial neoplasms. While often asymptomatic, they can cause or facilitate a wide range of diseases including opportunistic infections. The potential therapeutic value of specific neutralizing anticytokine autoantibodies has not been thoroughly investigated. Here we used mammalian cell display to isolate IL17A-specific antibodies from a thymoma patient with proven high-titer autoantibodies against the same. We identified 3 distinct clonotypes that efficiently neutralized IL17A in a cell-based in vitro assay. Their potencies were comparable to those of known neutralizing antibodies, including 2, AIN457 (secukinumab) and ixekizumab that are currently in clinical development for the treatment of various inflammatory disorders. These data clearly demonstrate that the human autoantibody repertoire can be mined for antibodies with high therapeutic potential for clinical development. C1 [Bauer, Monika; Fritzer, Andrea; Hanner, Markus; Nebenfuehr, Mario; Toepfer, Jorge Alejandro Sepulveda; Bauer, Anton; Meinke, Andreas] Valneva Austria GmbH, Vienna, Austria. [Rosen, Lindsey B.; Holland, Steven M.; Browne, Sarah K.] NIAID, Bethesda, MD 20892 USA. [Buser, Regula B.] ImmunoQure Res AG, Schlieren, Switzerland. [Maudrich, Melanie] Univ Zurich Hosp, Dept Dermatol, CH-8091 Zurich, Switzerland. [Mangold, Susanne] Andreasklin, Synlab, Cham, Switzerland. [Beerli, Roger R.] NBE Therapeut LLC, Basel, Switzerland. RP Meinke, A (reprint author), Valneva Austria GmbH, Campus Vienna Bioctr 3, Vienna, Austria. EM andreas.meinke@valneva.com FU Division of Intramural Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health FX This work supported in part by the Division of Intramural Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health. NR 80 TC 1 Z9 1 U1 1 U2 4 PU LANDES BIOSCIENCE PI AUSTIN PA 1806 RIO GRANDE ST, AUSTIN, TX 78702 USA SN 1942-0862 EI 1942-0870 J9 MABS-AUSTIN JI mAbs PD DEC PY 2014 VL 6 IS 6 BP 1608 EP 1620 DI 10.4161/mabs.36292 PG 13 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA AX4BH UT WOS:000346878600025 PM 25484038 ER PT J AU You, XX Bian, C Zan, QJ Xu, X Liu, X Chen, JM Wang, JT Qiu, Y Li, WJ Zhang, XH Sun, Y Chen, SX Hong, WS Li, YX Cheng, SF Fan, GY Shi, CC Liang, J Tang, YT Yang, CY Ruan, ZQ Bai, J Peng, C Mu, Q Lu, J Fan, MJ Yang, S Huang, ZY Jiang, XT Fang, XD Zhang, GJ Zhang, Y Polgar, G Yu, H Li, J Liu, ZJ Zhang, GQ Ravi, V Coon, SL Wang, J Yang, HM Venkatesh, B Wang, J Shi, Q AF You, Xinxin Bian, Chao Zan, Qijie Xu, Xun Liu, Xin Chen, Jieming Wang, Jintu Qiu, Ying Li, Wujiao Zhang, Xinhui Sun, Ying Chen, Shixi Hong, Wanshu Li, Yuxiang Cheng, Shifeng Fan, Guangyi Shi, Chengcheng Liang, Jie Tang, Y. Tom Yang, Chengye Ruan, Zhiqiang Bai, Jie Peng, Chao Mu, Qian Lu, Jun Fan, Mingjun Yang, Shuang Huang, Zhiyong Jiang, Xuanting Fang, Xiaodong Zhang, Guojie Zhang, Yong Polgar, Gianluca Yu, Hui Li, Jia Liu, Zhongjian Zhang, Guoqiang Ravi, Vydianathan Coon, Steven L. Wang, Jian Yang, Huanming Venkatesh, Byrappa Wang, Jun Shi, Qiong TI Mudskipper genomes provide insights into the terrestrial adaptation of amphibious fishes SO NATURE COMMUNICATIONS LA English DT Article ID GENE-EXPRESSION; PERIOPHTHALMODON-SCHLOSSERI; BOLEOPHTHALMUS-BODDAERTI; RNA-SEQ; AMMONIA; RECEPTOR; HYPOXIA; TRANSCRIPTS; VERTEBRATES; DIVERGENCE AB Mudskippers are amphibious fishes that have developed morphological and physiological adaptations to match their unique lifestyles. Here we perform whole-genome sequencing of four representative mudskippers to elucidate the molecular mechanisms underlying these adaptations. We discover an expansion of innate immune system genes in the mudskippers that may provide defence against terrestrial pathogens. Several genes of the ammonia excretion pathway in the gills have experienced positive selection, suggesting their important roles in mudskippers' tolerance to environmental ammonia. Some vision-related genes are differentially lost or mutated, illustrating genomic changes associated with aerial vision. Transcriptomic analyses of mudskippers exposed to air highlight regulatory pathways that are up-or down-regulated in response to hypoxia. The present study provides a valuable resource for understanding the molecular mechanisms underlying water-to-land transition of vertebrates. C1 [You, Xinxin; Bian, Chao; Chen, Jieming; Qiu, Ying; Li, Wujiao; Zhang, Xinhui; Ruan, Zhiqiang; Bai, Jie; Peng, Chao; Yu, Hui; Li, Jia; Shi, Qiong] State Key Lab Agr Genom, Shenzhen Key Lab Marine Genom, Shenzhen 518083, Peoples R China. [You, Xinxin; Bian, Chao; Xu, Xun; Liu, Xin; Chen, Jieming; Wang, Jintu; Qiu, Ying; Zhang, Xinhui; Sun, Ying; Li, Yuxiang; Cheng, Shifeng; Fan, Guangyi; Shi, Chengcheng; Liang, Jie; Tang, Y. Tom; Yang, Chengye; Ruan, Zhiqiang; Bai, Jie; Peng, Chao; Mu, Qian; Lu, Jun; Yang, Shuang; Huang, Zhiyong; Jiang, Xuanting; Fang, Xiaodong; Zhang, Guojie; Zhang, Yong; Yu, Hui; Li, Jia; Wang, Jian; Yang, Huanming; Wang, Jun; Shi, Qiong] BGI Shenzhen, Shenzhen 518083, Peoples R China. [Zan, Qijie] Shenzhen Wild Anim Rescue Ctr, Shenzhen 518040, Peoples R China. [Chen, Shixi; Hong, Wanshu] Xiamen Univ, Coll Ocean & Earth Sci, Xiamen 361005, Peoples R China. [Lu, Jun; Shi, Qiong] Shenzhen BGI Fisheries Sci & Tech Co Ltd, Shenzhen 518083, Peoples R China. [Fan, Mingjun; Yang, Shuang; Shi, Qiong] BGI Wuhan, Ctr Fish Genom, Wuhan 430075, Peoples R China. [Polgar, Gianluca] Univ Brunei Darussalam, Fac Sci, Environm & Life Sci Programme, BE-1410 Jln Tungku Link, Brunei. [Liu, Zhongjian; Zhang, Guoqiang] Orchid Conservat & Res Ctr Shenzhen, Shenzhen Key Lab Orchid Conservat & Utilizat, Shenzhen 518114, Peoples R China. [Ravi, Vydianathan; Venkatesh, Byrappa] ASTAR, Biopolis, Inst Mol & Cell Biol, Singapore 138673, Singapore. [Coon, Steven L.] NIH, Mol Genom Lab, Bethesda, MD 20892 USA. [Wang, Jian; Yang, Huanming] James D Watson Inst Genome Sci, Hangzhou 310008, Zhejiang, Peoples R China. [Yang, Huanming; Wang, Jun] King Abdulaziz Univ, Princess Al Jawhara Ctr Excellence Res Hereditary, Jeddah 21413, Saudi Arabia. [Wang, Jun] Univ Copenhagen, Dept Biol, DK-2200 Copenhagen, Denmark. RP Bian, C (reprint author), State Key Lab Agr Genom, Shenzhen Key Lab Marine Genom, Shenzhen 518083, Peoples R China. EM bianchao@genomics.cn; wangj@genomics.cn; shiqiong@genomics.cn RI Zhang, Guojie/B-6188-2014; ASTAR, IMCB/E-2320-2012; Wang, Jun/C-8434-2016; Vydianathan, Ravi/B-2759-2009; Wang, Jun/B-9503-2016; OI Venkatesh, Byrappa/0000-0003-3620-0277; Zhang, Guojie/0000-0001-6860-1521; Wang, Jun/0000-0002-8540-8931; Vydianathan, Ravi/0000-0003-0807-7697; Wang, Jun/0000-0002-2113-5874; Polgar, Gianluca/0000-0002-4901-6287 FU Shenzhen Key Lab of Marine Genomics [CXB201108250095A]; China National High-Technology Research and Development Program [2012AA10A407]; State Key Laboratory of Agricultural Genomics [ZDSY20120618171817275]; Biomedical Research Council of A*STAR, Singapore; Intramural Research Program of the Eunice Kennedy Shriver National Institute of Child Health and Human Development at the National Institutes of Health, USA; Xiamen University President Research Award [2013121044] FX We acknowledge L. Lin, R. You, C. Wang, H. Zhong and Yuen K. Ip for their help in collecting mudskipper samples, S. He, H. Ye, Y. Kawabata, A. Ishimatsu and J. Chung for fruitful discussions; L. Goodman for manuscript revision. C. K. Ching provided the high-quality photo of mudskippers for the Featured image. This study was supported by grants from Shenzhen Key Lab of Marine Genomics (CXB201108250095A), China National High-Technology Research and Development Program (2012AA10A407) and State Key Laboratory of Agricultural Genomics (ZDSY20120618171817275) to Q. Shi. It was also supported in part by the Biomedical Research Council of A*STAR, Singapore (to B.V.), the Intramural Research Program of the Eunice Kennedy Shriver National Institute of Child Health and Human Development at the National Institutes of Health, USA (to S.L.C.) and the Xiamen University President Research Award (No. 2013121044) to S.C. NR 56 TC 15 Z9 15 U1 5 U2 49 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 DEC PY 2014 VL 5 AR 5594 DI 10.1038/ncomms6594 PG 8 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA AX9LO UT WOS:000347224500001 PM 25463417 ER PT J AU Omonijo, O Wongprayoon, P Ladenheim, B Mccoy, MT Govitrapong, P Jayanthi, S Cadet, JL AF Omonijo, Oluwaseyi Wongprayoon, Pawaris Ladenheim, Bruce Mccoy, Michael T. Govitrapong, Piyarat Jayanthi, Subramaniam Cadet, Jean Lud TI Differential effects of binge methamphetamine injections on the mRNA expression of histone deacetylases (HDACs) in the rat striatum SO NEUROTOXICOLOGY LA English DT Article DE Epigenetics; Sirtuins; Neurotoxicity; Gene expression ID INDUCED NEURONAL APOPTOSIS; MYOCYTE-ENHANCER FACTOR-2; DEPENDENT PROTEIN-KINASE; PHOSPHATE SYNTHETASE 1; GENE-EXPRESSION; ENDOPLASMIC-RETICULUM; INDUCED NEUROTOXICITY; UP-REGULATION; CLONING; SIRT5 AB Methamphetamine use disorder is characterized by recurrent binge episodes. Humans addicted to methamphetamine experience various degrees of cognitive deficits and show evidence of neurodegenerative processes in the brain. Binge injections of METH to rodents also cause significant toxic changes in the brain. In addition, this pattern of METH injections can alter gene expression in the dorsal striatum. Gene expression is regulated, in part, by histone deacetylation. We thus tested the possibility that METH toxic doses might cause changes in the mRNA levels of histone deacetylases (HDACs). We found that METH did produce significant decreases in the mRNA expression of HDAC8, which is a class I HDAC. METH also decreased expression of HDAC6, HDAC9, and HDAC10 that are class II HDACs. The expression of the class IV HDAC, HDAC11, was also suppressed by METH. The expression of Sirt2, Sirt5, and Sirt6 that are members of class III HDACs was also downregulated by METH injections. Our findings implicate changes in HDAC expression may be an early indicator of impending METH-induced neurotoxicity in the striatum. This idea is consistent with the accumulated evidence that some HDACs are involved in neurodegenerative processes in the brain. Published by Elsevier Inc. C1 [Omonijo, Oluwaseyi; Ladenheim, Bruce; Mccoy, Michael T.; Jayanthi, Subramaniam; Cadet, Jean Lud] NIDA Intramural Res Program, Mol Neuropsychiat Res Branch, Baltimore, MD 21224 USA. [Wongprayoon, Pawaris; Govitrapong, Piyarat] Mahidol Univ, Inst Mol Biosci, Res Ctr Neurosci, Bangkok 10700, Thailand. RP Cadet, JL (reprint author), NIDA Intramural Res Program, Mol Neuropsychiat Res Branch, 251 Bayview Blvd, Baltimore, MD 21224 USA. EM jcadet@intra.nida.nih.gov FU Intramural Research Program of the DHHS/NIH/NIDA; Thailand Research Fund (TRF) - Royal Golden Jubilee Ph.D. Program; Mahidol University FX This research was supported by funds of the Intramural Research Program of the DHHS/NIH/NIDA. Pawaris Wongprayoon and Dr. Piyarat Govitrapong were supported by funds from the Thailand Research Fund (TRF) - Royal Golden Jubilee Ph.D. Program and Mahidol University. The authors also thank the comments of two reviewers who help make this a better paper. NR 81 TC 5 Z9 5 U1 1 U2 8 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0161-813X EI 1872-9711 J9 NEUROTOXICOLOGY JI Neurotoxicology PD DEC PY 2014 VL 45 BP 178 EP 184 DI 10.1016/j.neuro.2014.10.008 PG 7 WC Neurosciences; Pharmacology & Pharmacy; Toxicology SC Neurosciences & Neurology; Pharmacology & Pharmacy; Toxicology GA AX5GQ UT WOS:000346955100019 PM 25452209 ER PT J AU Malik, N Efthymiou, AG Mather, K Chester, N Wang, XT Nath, A Rao, MS Steiner, JP AF Malik, Nasir Efthymiou, Anastasia G. Mather, Karly Chester, Nathaniel Wang, Xiantao Nath, Avindra Rao, Mahendra S. Steiner, Joseph P. TI Compounds with species and cell type specific toxicity identified in a 2000 compound drug screen of neural stem cells and rat mixed cortical neurons SO NEUROTOXICOLOGY LA English DT Article DE Neurotoxicity screening; Neural stem cells; Cardiac glycosides ID DEFINED CONDITIONS; SMALL-MOLECULE; NEUROTOXICITY; GENERATION; EFFICIENT; LIGAND; DIFFERENTIATION; DERIVATION; INHIBITION; EXPRESSION AB Human primary neural tissue is a vital component for the quick and simple determination of chemical compound neurotoxicity in vitro. In particular, such tissue would be ideal for high-throughput screens that can be used to identify novel neurotoxic or neurotherapeutic compounds. We have previously established a high-throughput screening platform using human induced pluripotent stem cell (iPSC)-derived neural stem cells (NSCs) and neurons. In this study, we conducted a 2000 compound screen with human NSCs and rat cortical cells to identify compounds that are selectively toxic to each group. Approximately 100 of the tested compounds showed specific toxicity to human NSCs. A secondary screen of a small subset of compounds from the primary screen on human iPSCs, NSC-derived neurons, and fetal astrocytes validated the results from >80% of these compounds with some showing cell specific toxicity. Amongst those compounds were several cardiac glycosides, all of which were selectively toxic to the human cells. As the screen was able to reliably identify neurotoxicants, many with species and cell-type specificity, this study demonstrates the feasibility of this NSC-driven platform for higher-throughput neurotoxicity screens. Published by Elsevier Inc. C1 [Malik, Nasir; Efthymiou, Anastasia G.; Wang, Xiantao; Rao, Mahendra S.] NIAMS, NIH, Bethesda, MD 20892 USA. [Mather, Karly; Chester, Nathaniel; Nath, Avindra; Steiner, Joseph P.] NINDS, NIH, Bethesda, MD 20892 USA. [Rao, Mahendra S.] Natl Inst Hlth Ctr Regenerat Med, Natl Inst Hlth, Bethesda, MD USA. RP Malik, N (reprint author), NIAMS, NIH, 50 South Dr,Room 1142, Bethesda, MD 20892 USA. EM malikn@mail.nih.gov OI Efthymiou, Anastasia/0000-0002-1769-5078 FU NIH Common Fund FX This work was funded by the NIH Common Fund. NR 37 TC 9 Z9 9 U1 1 U2 12 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0161-813X EI 1872-9711 J9 NEUROTOXICOLOGY JI Neurotoxicology PD DEC PY 2014 VL 45 BP 192 EP 200 DI 10.1016/j.neuro.2014.10.007 PG 9 WC Neurosciences; Pharmacology & Pharmacy; Toxicology SC Neurosciences & Neurology; Pharmacology & Pharmacy; Toxicology GA AX5GQ UT WOS:000346955100021 PM 25454721 ER PT J AU Buckland, RJ Watt, DL Chittoor, B Nilsson, AK Kunkel, TA Chabes, A AF Buckland, Robert J. Watt, Danielle L. Chittoor, Balasubramanyam Nilsson, Anna Karin Kunkel, Thomas A. Chabes, Andrei TI Increased and Imbalanced dNTP Pools Symmetrically Promote Both Leading and Lagging Strand Replication Infidelity SO PLOS GENETICS LA English DT Article ID DNA MISMATCH-REPAIR; ESCHERICHIA-COLI; SACCHAROMYCES-CEREVISIAE; RIBONUCLEOTIDE REDUCTASE; SPONTANEOUS MUTATION; BUDDING YEAST; CANCER; GENE; FORK; MUTAGENESIS AB The fidelity of DNA replication requires an appropriate balance of dNTPs, yet the nascent leading and lagging strands of the nuclear genome are primarily synthesized by replicases that differ in subunit composition, protein partnerships and biochemical properties, including fidelity. These facts pose the question of whether imbalanced dNTP pools differentially influence leading and lagging strand replication fidelity. Here we test this possibility by examining strand-specific replication infidelity driven by a mutation in yeast ribonucleotide reductase, rnr1-Y285A, that leads to elevated dTTP and dCTP concentrations. The results for the CAN1 mutational reporter gene present in opposite orientations in the genome reveal that the rates, and surprisingly even the sequence contexts, of replication errors are remarkably similar for leading and lagging strand synthesis. Moreover, while many mismatches driven by the dNTP pool imbalance are efficiently corrected by mismatch repair, others are repaired less efficiently, especially those in sequence contexts suggesting reduced proofreading due to increased mismatch extension driven by the high dTTP and dCTP concentrations. Thus the two DNA strands of the nuclear genome are at similar risk of mutations resulting from this dNTP pool imbalance, and this risk is not completely suppressed even when both major replication error correction mechanisms are genetically intact. C1 [Buckland, Robert J.; Chittoor, Balasubramanyam; Nilsson, Anna Karin; Chabes, Andrei] Umea Univ, Dept Med Biochem & Biophys, S-90187 Umea, Sweden. [Buckland, Robert J.; Chabes, Andrei] Umea Univ, Lab Mol Infect Med Sweden MIMS, Umea, Sweden. [Watt, Danielle L.; Kunkel, Thomas A.] NIEHS, Mol Genet Lab, NIH, DHHS, Res Triangle Pk, NC 27709 USA. [Watt, Danielle L.; Kunkel, Thomas A.] NIEHS, Struct Biol Lab, NIH, DHHS, Res Triangle Pk, NC 27709 USA. RP Buckland, RJ (reprint author), Umea Univ, Dept Med Biochem & Biophys, S-90187 Umea, Sweden. EM andrei.chabes@medchem.umu.se RI Buckland, Robert/L-6137-2014 OI Buckland, Robert/0000-0001-9749-5422 FU Division of Intramural Research of the NIH, NIEHS [Z01 ES065070]; Knut and Alice Wallenberg Foundation; Swedish Foundation for Strategic Research; Swedish Cancer Society FX This work was supported by Project Z01 ES065070 to TAK from the Division of Intramural Research of the NIH, NIEHS, and by The Knut and Alice Wallenberg Foundation, the Swedish Foundation for Strategic Research and the Swedish Cancer Society to AC. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 42 TC 11 Z9 11 U1 0 U2 7 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA SN 1553-7390 EI 1553-7404 J9 PLOS GENET JI PLoS Genet. PD DEC PY 2014 VL 10 IS 12 AR e1004846 DI 10.1371/journal.pgen.1004846 PG 8 WC Genetics & Heredity SC Genetics & Heredity GA AX0NW UT WOS:000346649900047 PM 25474551 ER PT J AU Bastian, H AF Bastian, Hilda TI A Stronger Post-Publication Culture Is Needed for Better Science SO PLOS MEDICINE LA English DT Editorial Material ID MEDICAL LITERATURE; GENDER; LANGUAGE; AUTHORS; WOMEN C1 NIH, Natl Ctr Biotechnol Informat, Natl Lib Med, Bethesda, MD 20892 USA. RP Bastian, H (reprint author), NIH, Natl Ctr Biotechnol Informat, Natl Lib Med, Bldg 10, Bethesda, MD 20892 USA. EM hilda.bastian@nih.gov OI Bastian, Hilda/0000-0001-8544-7386 FU Intramural NIH HHS NR 33 TC 7 Z9 7 U1 0 U2 9 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA SN 1549-1676 J9 PLOS MED JI PLos Med. PD DEC PY 2014 VL 11 IS 12 AR e1001772 DI 10.1371/journal.pmed.1001772 PG 3 WC Medicine, General & Internal SC General & Internal Medicine GA AX5ZD UT WOS:000347002300010 PM 25548904 ER PT J AU Kim, JH Sohn, BH Lee, HS Kim, SB Yoo, JE Park, YY Jeong, W Lee, SS Park, ES Kaseb, A Kim, BH Kim, WB Yeon, JE Byun, KS Chu, IS Kim, SS Wang, XW Thorgeirsson, SS Luk, JM Kang, KJ Heo, J Park, YN Lee, JS AF Kim, Ji Hoon Sohn, Bo Hwa Lee, Hyun-Sung Kim, Sang-Bae Yoo, Jeong Eun Park, Yun-Yong Jeong, Woojin Lee, Sung Sook Park, Eun Sung Kaseb, Ahmed Kim, Baek Hui Kim, Wan Bae Yeon, Jong Eun Byun, Kwan Soo Chu, In-Sun Kim, Sung Soo Wang, Xin Wei Thorgeirsson, Snorri S. Luk, John M. Kang, Koo Jeong Heo, Jeonghoon Park, Young Nyun Lee, Ju-Seog TI Genomic Predictors for Recurrence Patterns of Hepatocellular Carcinoma: Model Derivation and Validation SO PLOS MEDICINE LA English DT Article ID GENE-EXPRESSION; INTRAHEPATIC RECURRENCE; RISK-FACTORS; THERAPEUTIC TARGET; CURATIVE RESECTION; SIGNALING PATHWAY; STAT3 ACTIVATION; UNITED-STATES; TUMOR-GROWTH; LIVER AB Background: Typically observed at 2 y after surgical resection, late recurrence is a major challenge in the management of hepatocellular carcinoma (HCC). We aimed to develop a genomic predictor that can identify patients at high risk for late recurrence and assess its clinical implications. Methods and Findings: Systematic analysis of gene expression data fromhuman liver undergoing hepatic injury and regeneration revealed a 233-gene signature that was significantly associated with late recurrence of HCC. Using this signature, we developed a prognostic predictor that can identify patients at high risk of late recurrence, and tested and validated the robustness of the predictor in patients (n = 396) who underwent surgery between 1990 and 2011 at four centers (210 recurrences during a median of 3.7 y of follow-up). In multivariate analysis, this signature was the strongest risk factor for late recurrence (hazard ratio, 2.2; 95% confidence interval, 1.3-3.7; p = 0.002). In contrast, our previously developed tumor-derived 65-gene risk score was significantly associated with early recurrence (p = 0.005) but not with late recurrence (p = 0.7). In multivariate analysis, the 65-gene risk score was the strongest risk factor for very early recurrence (< 1 y after surgical resection) (hazard ratio, 1.7; 95% confidence interval, 1.1-2.6; p = 0.01). The potential significance of STAT3 activation in late recurrence was predicted by gene network analysis and validated later. We also developed and validated 4- and 20-gene predictors from the full 233-gene predictor. The main limitation of the study is that most of the patients in our study were hepatitis B virus-positive. Further investigations are needed to test our prediction models in patients with different etiologies of HCC, such as hepatitis C virus. Conclusions: Two independently developed predictors reflected well the differences between early and late recurrence of HCC at the molecular level and provided new biomarkers for risk stratification. C1 [Kim, Ji Hoon; Sohn, Bo Hwa; Lee, Hyun-Sung; Kim, Sang-Bae; Lee, Ju-Seog] Univ Texas MD Anderson Canc Ctr, Div Canc Med, Dept Syst Biol, Houston, TX 77030 USA. [Kim, Ji Hoon; Sohn, Bo Hwa; Lee, Hyun-Sung; Kim, Sang-Bae; Lee, Ju-Seog] Univ Texas MD Anderson Canc Ctr, Kleberg Ctr Mol Markers, Houston, TX 77030 USA. [Kim, Ji Hoon; Yeon, Jong Eun; Byun, Kwan Soo] Korea Univ, Coll Med, Dept Internal Med, Div Gastroenterol & Hepatol, Seoul 136705, South Korea. [Yoo, Jeong Eun; Park, Young Nyun] Yonsei Univ, Coll Med, Dept Pathol, Seoul, South Korea. [Yoo, Jeong Eun; Park, Young Nyun] Yonsei Univ, Coll Med, Brain Korea Project Med Sci 21, Seoul, South Korea. [Park, Yun-Yong] Univ Ulsan, Coll Med, Dept Med, ASAN Inst Life Sci,Asan Med Ctr, Seoul, South Korea. [Jeong, Woojin] Ewha Womans Univ, Dept Life Sci, Div Life & Pharmaceut Sci, Ctr Cell Signaling & Drug Discovery Res, Seoul, South Korea. [Lee, Sung Sook] Inje Univ, Haeundae Paik Hosp, Dept Hematol Oncol, Pusan, South Korea. [Park, Eun Sung] Yonsei Univ, Coll Med, Inst Med Convergence, Seoul, South Korea. [Kaseb, Ahmed] Univ Texas MD Anderson Canc Ctr, Div Canc Med, Dept GI Med Oncol, Houston, TX 77030 USA. [Kim, Baek Hui] Korea Univ, Coll Med, Dept Internal Med, Dept Pathol, Seoul 136705, South Korea. [Kim, Wan Bae] Korea Univ, Coll Med, Dept Internal Med, Dept Surg, Seoul 136705, South Korea. [Chu, In-Sun] Korea Res Inst Biosci & Biotechnol, Korean Bioinformat Ctr, Taejon, South Korea. [Kim, Sung Soo; Lee, Ju-Seog] Kyung Hee Univ, Med Res Ctr, Dept Biochem & Mol Biol, Seoul, South Korea. [Kim, Sung Soo; Lee, Ju-Seog] Kyung Hee Univ, Sch Med, Inst Biomed Sci, Seoul, South Korea. [Wang, Xin Wei] NCI, Human Carcinogenesis Lab, NIH, Bethesda, MD 20892 USA. [Thorgeirsson, Snorri S.] NCI, Expt Carcinogenesis Lab, NIH, Bethesda, MD 20892 USA. [Luk, John M.] Natl Univ Singapore, Dept Pharmacol, Singapore 117548, Singapore. [Kang, Koo Jeong] Keimyung Univ, Sch Med, Dept Surg, Taegu, South Korea. [Heo, Jeonghoon] Kosin Univ, Coll Med, Dept Mol Biol, Pusan, South Korea. [Heo, Jeonghoon] Kosin Univ, Coll Med, Dept Immunol, Pusan, South Korea. RP Kim, JH (reprint author), Univ Texas MD Anderson Canc Ctr, Div Canc Med, Dept Syst Biol, Houston, TX 77030 USA. EM jlee@mdanderson.org RI Wang, Xin/B-6162-2009; Luk, John/A-4085-2008; OI Luk, John/0000-0002-6323-7940; Lee, Hyun-Sung/0000-0001-8259-046X FU MD Anderson Sister Institute Network Fund; Bio & Medical Technology Development Program [M10642040002-07N4204-00210]; Scientific Research Center Program [2012R1A5A1048236]; GlaxoSmithKline Research Fund of the Korean Association for the Study of the Liver; Center for Cancer Research, National Cancer Institute; National Research Foundation (NSF) of Korea by the Korea government (Ministry of Science, ICT, and Future Planning) [2013R1A2A2A05005990] FX This work is supported in part by 2011 and 2012 cycle of MD Anderson Sister Institute Network Fund (JSL); Bio & Medical Technology Development Program Grant M10642040002-07N4204-00210 (WJ); Scientific Research Center Program Grant 2012R1A5A1048236 (WJ); the GlaxoSmithKline Research Fund of the Korean Association for the Study of the Liver (JHK); the intramural program of the Center for Cancer Research, National Cancer Institute (XWW and SST); and the National Research Foundation (NSF); of Korea grant by the Korea government (Ministry of Science, ICT, and Future Planning) (No. 2013R1A2A2A05005990) (YNP). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 55 TC 8 Z9 8 U1 0 U2 3 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA SN 1549-1676 J9 PLOS MED JI PLos Med. PD DEC PY 2014 VL 11 IS 12 AR e1001770 DI 10.1371/journal.pmed.1001770 PG 16 WC Medicine, General & Internal SC General & Internal Medicine GA AX5ZD UT WOS:000347002300008 PM 25536056 ER PT J AU Schwarz, A Medrano-Mercado, N Schaub, GA Struchiner, CJ Bargues, MD Levy, MZ Ribeiro, JMC AF Schwarz, Alexandra Medrano-Mercado, Nora Schaub, Guenter A. Struchiner, Claudio J. Dolores Bargues, M. Levy, Michael Z. Ribeiro, Jose M. C. TI An Updated Insight into the Sialotranscriptome of Triatoma infestans: Developmental Stage and Geographic Variations SO PLOS NEGLECTED TROPICAL DISEASES LA English DT Article ID PANSTRONGYLUS-MEGISTUS HEMIPTERA; INDUCED PLATELET-AGGREGATION; BUG RHODNIUS-PROLIXUS; CHAGAS-DISEASE; NUCLEAR RDNA; SALIVARY PROTEINS; PHYLOGENETIC-RELATIONSHIPS; BRAZILIAN POPULATIONS; ANOPHELES-GAMBIAE; SERINE-PROTEASE AB Background: Triatoma infestans is the main vector of Chagas disease in South America. As in all hematophagous arthropods, its saliva contains a complex cocktail that assists blood feeding by preventing platelet aggregation and blood clotting and promoting vasodilation. These salivary components can be immunologically recognized by their vector's hosts and targeted with antibodies that might disrupt blood feeding. These antibodies can be used to detect vector exposure using immunoassays. Antibodies may also contribute to the fast evolution of the salivary cocktail. Methodology: Salivary gland cDNA libraries from nymphal and adult T. infestans of breeding colonies originating from different locations (Argentina, Chile, Peru and Bolivia), and cDNA libraries originating from F1 populations of Bolivia, were sequenced using Illumina technology. Coding sequences (CDS) were extracted from the assembled reads, the numbers of reads mapped to these CDS, sequences were functionally annotated and polymorphisms determined. Main findings/Significance: Over five thousand CDS, mostly full length or near full length, were publicly deposited on GenBank. Transcripts that were over 10-fold overexpressed from different geographical regions, or from different developmental stages were identified. Polymorphisms were mapped to derived coding sequences, and found to vary between developmental instars and geographic origin of the biological material. This expanded sialome database from T. infestans should be of assistance in future proteomic work attempting to identify salivary proteins that might be used as epidemiological markers of vector exposure, or proteins of pharmacological interest. C1 [Schwarz, Alexandra] Acad Sci Czech Republic, Inst Parasitol, Ctr Biol, CR-37005 Ceske Budejovice, Czech Republic. [Medrano-Mercado, Nora] Univ Mayor San Simon, Lab Chagas Dis & Immunoparasitol, Cochabamba, Bolivia. [Schaub, Guenter A.] Ruhr Univ Bochum, Zool Parasitol Grp, Bochum, Germany. [Struchiner, Claudio J.] Fiocruz MS, Escola Nacl Saude Publ, BR-21045900 Rio De Janeiro, Brazil. [Dolores Bargues, M.] Univ Valencia, Fac Farm, Dept Parasitol, E-46010 Valencia, Spain. [Levy, Michael Z.] Univ Peruana Cayetano Heredia, Sede De Arequipa, Arequipa, Peru. [Levy, Michael Z.] Univ Penn, Sch Med, Dept Biostat & Epidemiol, Ctr Clin Epidemiol & Biostat, Philadelphia, PA 19104 USA. [Ribeiro, Jose M. C.] NIAID, Lab Malaria & Vector Res, NIH, Rockville, MD USA. RP Schwarz, A (reprint author), Acad Sci Czech Republic, Inst Parasitol, Ctr Biol, Branisovska 31, CR-37005 Ceske Budejovice, Czech Republic. EM jribeiro@niaid.nih.gov OI Ribeiro, Jose/0000-0002-9107-0818 FU National Institute of Allergy and Infectious Diseases [ZIA AI000810-16]; Ministry of Education, Youth and Sports of the Czech Republic [LH12002]; Academy of Sciences of the Czech Republic [Z60220518]; RETICS, Red de Investigacion Cooperativa en Enfermedades Tropicales - RICET [RD12/0018/0013]; VI National Plan of I+D+I, ISCIII - Subdireccion General de Redes y Centros de Investigacion Cooperativa; Ministry of Health, Madrid, Spain; PROMETEO Project, Programa of Ayudas para Grupos de Investigacion de Excelencia, Generalitat Valenciana, Valencia, Spain [2012/042] FX This work was partially supported by grants ZIA AI000810-16 from the National Institute of Allergy and Infectious Diseases to JMCR, by grant KONTAKT II no. LH12002 from the Ministry of Education, Youth and Sports of the Czech Republic and grant no. Z60220518 from the Academy of Sciences of the Czech Republic to AS, and project No. RD12/0018/0013 of RETICS, Red de Investigacion Cooperativa en Enfermedades Tropicales - RICET, VI National Plan of I+D+I 2008-2011, ISCIII - Subdireccion General de Redes y Centros de Investigacion Cooperativa, Ministry of Health, Madrid, Spain and PROMETEO Project No. 2012/042, Programa of Ayudas para Grupos de Investigacion de Excelencia, Generalitat Valenciana, Valencia, Spain to MDB. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 68 TC 5 Z9 5 U1 2 U2 11 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 DEC PY 2014 VL 8 IS 12 AR e3372 DI 10.1371/journal.pntd.0003372 PG 15 WC Infectious Diseases; Parasitology; Tropical Medicine SC Infectious Diseases; Parasitology; Tropical Medicine GA AX1IM UT WOS:000346701000045 PM 25474469 ER PT J AU Malinowski, JR Denny, JC Bielinski, SJ Basford, MA Bradford, Y Peissig, PL Carrell, D Crosslin, DR Pathak, J Rasmussen, L Pacheco, J Kho, A Newton, KM Li, RL Kullo, IJ Chute, CG Chisholm, RL Jarvik, GP Larson, EB McCarty, CA Masys, DR Roden, DM de Andrade, M Ritchie, MD Crawford, DC AF Malinowski, Jennifer R. Denny, Joshua C. Bielinski, Suzette J. Basford, Melissa A. Bradford, Yuki Peissig, Peggy L. Carrell, David Crosslin, David R. Pathak, Jyotishman Rasmussen, Luke Pacheco, Jennifer Kho, Abel Newton, Katherine M. Li, Rongling Kullo, Iftikhar J. Chute, Christopher G. Chisholm, Rex L. Jarvik, Gail P. Larson, Eric B. McCarty, Catherine A. Masys, Daniel R. Roden, Dan M. de Andrade, Mariza Ritchie, Marylyn D. Crawford, Dana C. TI Genetic Variants Associated with Serum Thyroid Stimulating Hormone (TSH) Levels in European Americans and African Americans from the eMERGE Network SO PLOS ONE LA English DT Article ID GENOME-WIDE ASSOCIATION; ELECTRONIC MEDICAL-RECORDS; REFERENCE LIMITS; NATIONAL-HEALTH; TWIN COHORT; FREE T4; POPULATION; CANCER; LOCI; METAANALYSIS AB Thyroid stimulating hormone (TSH) hormone levels are normally tightly regulated within an individual; thus, relatively small variations may indicate thyroid disease. Genome-wide association studies (GWAS) have identified variants in PDE8B and FOXE1 that are associated with TSH levels. However, prior studies lacked racial/ethnic diversity, limiting the generalization of these findings to individuals of non-European ethnicities. The Electronic Medical Records and Genomics (eMERGE) Network is a collaboration across institutions with biobanks linked to electronic medical records (EMRs). The eMERGE Network uses EMR-derived phenotypes to perform GWAS in diverse populations for a variety of phenotypes. In this report, we identified serum TSH levels from 4,501 European American and 351 African American euthyroid individuals in the eMERGE Network with existing GWAS data. Tests of association were performed using linear regression and adjusted for age, sex, body mass index (BMI), and principal components, assuming an additive genetic model. Our results replicate the known association of PDE8B with serum TSH levels in European Americans (rs2046045 p=1.85x10(-17), beta=0.09). FOXE1 variants, associated with hypothyroidism, were not genome-wide significant (rs10759944: p=1.08x10(-6), beta=-0.05). No SNPs reached genome-wide significance in African Americans. However, multiple known associations with TSH levels in European ancestry were nominally significant in African Americans, including PDE8B (rs2046045 p=0.03, beta=-0.09), VEGFA (rs11755845 p=0.01, beta=-0.13), and NFIA (rs334699 p=1.50x10(-3), beta=-0.17). We found little evidence that SNPs previously associated with other thyroid-related disorders were associated with serum TSH levels in this study. These results support the previously reported association between PDE8B and serum TSH levels in European Americans and emphasize the need for additional genetic studies in more diverse populations. C1 [Denny, Joshua C.; Masys, Daniel R.; Ritchie, Marylyn D.] Vanderbilt Univ, Dept Biomed Informat, Nashville, TN 37235 USA. [Denny, Joshua C.; Roden, Dan M.] Vanderbilt Univ, Dept Med, Nashville, TN USA. [Ritchie, Marylyn D.; Crawford, Dana C.] Vanderbilt Univ, Dept Mol Physiol & Biophys, Nashville, TN 37232 USA. [Malinowski, Jennifer R.; Bradford, Yuki; Ritchie, Marylyn D.; Crawford, Dana C.] Vanderbilt Univ, Ctr Human Genet Res, Nashville, TN 37235 USA. [Bielinski, Suzette J.] Mayo Clin, Div Epidemiol, Dept Hlth Sci Res, Rochester, MN USA. [Basford, Melissa A.] Vanderbilt Univ, Res Off, Nashville, TN 37235 USA. [Pathak, Jyotishman; Chute, Christopher G.; de Andrade, Mariza] Mayo Clin, Div Biomed Stat & Informat, Dept Hlth Sci Res, Rochester, MN USA. [Peissig, Peggy L.; Rasmussen, Luke] Marshfield Clin Res Fdn, Biomed Informat Res Ctr, Marshfield, WI USA. [Carrell, David; Newton, Katherine M.; Larson, Eric B.] Grp Hlth Res Inst, Seattle, WA USA. [Pacheco, Jennifer; Kho, Abel] Northwestern Univ, Dept Med, Chicago, IL 60611 USA. [Li, Rongling] NHGRI, Div Genom Med, Bethesda, MD 20892 USA. [Kullo, Iftikhar J.] Mayo Clin, Div Cardiovasc Dis, Dept Hlth Sci Res, Rochester, MN USA. [Chisholm, Rex L.] Northwestern Univ, Ctr Genet Med, Chicago, IL 60611 USA. [McCarty, Catherine A.] Essentia Inst Rural Hlth, Duluth, MN USA. [Roden, Dan M.] Vanderbilt Univ, Dept Pharmacol, Nashville, TN USA. [Crosslin, David R.; Jarvik, Gail P.] Univ Washington, Dept Med Med Genet, Seattle, WA 98195 USA. [Crosslin, David R.; Jarvik, Gail P.] Univ Washington, Dept Genome Sci, Seattle, WA 98195 USA. RP Crawford, DC (reprint author), Vanderbilt Univ, Dept Mol Physiol & Biophys, Nashville, TN 37232 USA. EM dana.crawford@case.edu RI Bielinski, Suzette/A-2238-2009; OI Bielinski, Suzette/0000-0002-2905-5430; Rasmussen, Luke/0000-0002-4497-8049 FU NHGRI; NIGMS [U01HG04599, U01HG006379, U01HG004610, U01HG006375, U01HG004608, U01HG006389, U01HG004609, U01HG006388, U01HG04603, U01HG006378, U01HG006385, U01HG006382, U01HG006380, U01HG006830, U01HG006828]; Group Health/UW ADPR/ACT [UO1 AG 0681] FX Funding: The eMERGE Network is funded by NHGRI, with additional funding from NIGMS through the following grants: U01HG04599 and U01HG006379 to Mayo Clinic; U01HG004610 and U01HG006375 to Group Health Cooperative; U01HG004608 to Marshfield Clinic; U01HG006389 to Essentia Institute of Rural Health; U01HG004609 and U01HG006388 to Northwestern University; U01HG04603 and U01HG006378 to Vanderbilt University; U01HG006385 to the Coordinating Center; U01HG006382 to Geisinger Clinic; U01HG006380 to Icahn School of Medicine at Mount Sinai; U01HG006830 to The Children's Hospital of Philadelphia; and U01HG006828 to Cincinnati Children's Hospital and Boston Children's Hospital. Group Health/University of Washington received additional funding through Group Health/UW ADPR/ACT grant UO1 AG 0681. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 50 TC 4 Z9 4 U1 0 U2 5 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA SN 1932-6203 J9 PLOS ONE JI PLoS One PD DEC 1 PY 2014 VL 9 IS 12 AR e111301 DI 10.1371/journal.pone.0111301 PG 21 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA AX7SK UT WOS:000347114900008 PM 25436638 ER PT J AU Peters, NC Pagan, AJ Lawyer, PG Hand, TW Roma, EH Stamper, LW Romano, A Sacks, DL AF Peters, Nathan C. Pagan, Antonio J. Lawyer, Phillip G. Hand, Timothy W. Roma, Eric Henrique Stamper, Lisa W. Romano, Audrey Sacks, David L. TI Chronic Parasitic Infection Maintains High Frequencies of Short-Lived Ly6C(+)CD4(+) Effector T Cells That Are Required for Protection against Re-infection SO PLOS PATHOGENS LA English DT Article ID LEISHMANIA-MAJOR INFECTION; TUBERCULOSIS INFECTION; CONCOMITANT IMMUNITY; IMMUNOLOGICAL MEMORY; PERSISTENCE; RESPONSES; CD4(+); MIGRATION; ANTIBODY; TRANSMISSION AB In contrast to the ability of long-lived CD8(+) memory T cells to mediate protection against systemic viral infections, the relationship between CD4(+) T cell memory and acquired resistance against infectious pathogens remains poorly defined. This is especially true for T helper 1 (Th1) concomitant immunity, in which protection against reinfection coincides with a persisting primary infection. In these situations, pre-existing effector CD4 T cells generated by ongoing chronic infection, not memory cells, may be essential for protection against reinfection. We present a systematic study of the tissue homing properties, functionality, and life span of subsets of memory and effector CD4 T cells activated in the setting of chronic Leishmania major infection in resistant C57Bl/6 mice. We found that pre-existing, CD44(+)CD62L(-)T-bet(+)Ly6C(+) effector (T-EFF) cells that are short-lived in the absence of infection and are not derived from memory cells reactivated by secondary challenge, mediate concomitant immunity. Upon adoptive transfer and challenge, non-dividing Ly6C(+) T-EFF cells preferentially homed to the skin, released IFN-gamma, and conferred protection as compared to CD44(+)CD62L(-)Ly6C(-) effector memory or CD44(+)CD62L(+)Ly6C(-) central memory cells. During chronic infection, Ly6C(+) T-EFF cells were maintained at high frequencies via reactivation of TCM and the T-EFF themselves. The lack of effective vaccines for many chronic diseases may be because protection against infectious challenge requires the maintenance of pre-existing T-EFF cells, and is therefore not amenable to conventional, memory inducing, vaccination strategies. C1 [Peters, Nathan C.; Lawyer, Phillip G.; Hand, Timothy W.; Roma, Eric Henrique; Stamper, Lisa W.; Romano, Audrey; Sacks, David L.] NIAID, Intracellular Parasite Biol Sect, Parasit Dis Lab, NIH, Bethesda, MD 20892 USA. [Pagan, Antonio J.] Univ Minnesota, Sch Med, Dept Microbiol, Ctr Immunol, Minneapolis, MN 55455 USA. RP Peters, NC (reprint author), Univ Calgary, Fac Vet Med, Dept Comparat Biol & Expt Med, Dept Microbiol Immunol & Infect Dis,Cumming Sch M, Calgary, AB, Canada. EM ncpeters@ucalgary.ca RI Roma, Eric /E-2752-2014 OI Roma, Eric /0000-0001-5265-5277 FU National Institute of Allergy and Infectious Diseases FX This work was supported by the Intramural Research Program of the National Institute of Allergy and Infectious Diseases. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 42 TC 19 Z9 19 U1 2 U2 6 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 DEC PY 2014 VL 10 IS 12 AR e1004538 DI 10.1371/journal.ppat.1004538 PG 17 WC Microbiology; Parasitology; Virology SC Microbiology; Parasitology; Virology GA AX1JB UT WOS:000346702400026 PM 25473946 ER PT J AU Schuetz, A Deleage, C Sereti, I Rerknimitr, R Phanuphak, N Phuang-Ngern, Y Estes, JD Sandler, NG Sukhumvittaya, S Marovich, M Jongrakthaitae, S Akapirat, S Fletscher, JLK Kroon, E Dewar, R Trichavaroj, R Chomchey, N Douek, DC O'Connell, RJ Ngauy, V Robb, ML Phanuphak, P Michael, NL Excler, JL Kim, JH de Souza, MS Ananworanich, J AF Schuetz, Alexandra Deleage, Claire Sereti, Irini Rerknimitr, Rungsun Phanuphak, Nittaya Phuang-Ngern, Yuwadee Estes, Jacob D. Sandler, Netanya G. Sukhumvittaya, Suchada Marovich, Mary Jongrakthaitae, Surat Akapirat, Siriwat Fletscher, James L. K. Kroon, Eugene Dewar, Robin Trichavaroj, Rapee Chomchey, Nitiya Douek, Daniel C. O'Connell, Robert J. Ngauy, Viseth Robb, Merlin L. Phanuphak, Praphan Michael, Nelson L. Excler, Jean-Louis Kim, Jerome H. de Souza, Mark S. Ananworanich, Jintanat CA RV254 SEARCH 010 Study Grp RV304 SEARCH 013 Study Grp TI Initiation of ART during Early Acute HIV Infection Preserves Mucosal Th17 Function and Reverses HIV-Related Immune Activation SO PLOS PATHOGENS LA English DT Article ID HUMAN-IMMUNODEFICIENCY-VIRUS; REGULATORY T-CELLS; ANTIRETROVIRAL THERAPY; MICROBIAL TRANSLOCATION; TYPE-1 INFECTION; LYMPHOID-TISSUE; PERIPHERAL LYMPHOCYTES; LENTIVIRAL INFECTIONS; DISEASE PROGRESSION; GENE-EXPRESSION AB Mucosal Th17 cells play an important role in maintaining gut epithelium integrity and thus prevent microbial translocation. Chronic HIV infection is characterized by mucosal Th17 cell depletion, microbial translocation and subsequent immune-activation, which remain elevated despite antiretroviral therapy (ART) correlating with increased mortality. However, when Th17 depletion occurs following HIV infection is unknown. We analyzed mucosal Th17 cells in 42 acute HIV infection (AHI) subjects (Fiebig (F) stage I-V) with a median duration of infection of 16 days and the short-term impact of early initiation of ART. Th17 cells were defined as IL-17+ CD4+ T cells and their function was assessed by the co-expression of IL-22, IL-2 and IFN gamma. While intact during FI/II, depletion of mucosal Th17 cell numbers and function was observed during FIII correlating with local and systemic markers of immune-activation. ART initiated at FI/II prevented loss of Th17 cell numbers and function, while initiation at FIII restored Th17 cell numbers but not their polyfunctionality. Furthermore, early initiation of ART in FI/II fully reversed the initially observed mucosal and systemic immune-activation. In contrast, patients treated later during AHI maintained elevated mucosal and systemic CD8+ T-cell activation post initiation of ART. These data support a loss of Th17 cells at early stages of acute HIV infection, and highlight that studies of ART initiation during early AHI should be further explored to assess the underlying mechanism of mucosal Th17 function preservation. C1 [Schuetz, Alexandra; Phuang-Ngern, Yuwadee; Sukhumvittaya, Suchada; Jongrakthaitae, Surat; Akapirat, Siriwat; Kroon, Eugene; Trichavaroj, Rapee; O'Connell, Robert J.; Ngauy, Viseth; de Souza, Mark S.] Armed Forces Res Inst Med Sci US Component, Dept Retrovirol, Bangkok, Thailand. [Schuetz, Alexandra; Robb, Merlin L.; Excler, Jean-Louis; Ananworanich, Jintanat] Henry M Jackson Fdn Adv Mil Med, Bethesda, MD USA. [Deleage, Claire; Estes, Jacob D.] Frederick Natl Lab Canc Res, Leidos Biomed Res Inc, AIDS & Canc Virus Program, Frederick, MD USA. [Sereti, Irini] NIAID, Clin & Mol Retrovirol Sect, Immunoregulat Lab, NIH, Bethesda, MD 20892 USA. [Rerknimitr, Rungsun; Phanuphak, Praphan] Chulalongkorn Univ, Fac Med, Dept Med, Bangkok 10330, Thailand. [Phanuphak, Nittaya; Fletscher, James L. K.; Kroon, Eugene; Chomchey, Nitiya; Phanuphak, Praphan; Kim, Jerome H.; de Souza, Mark S.; Ananworanich, Jintanat] SEARCH, Bangkok, Thailand. [Phanuphak, Nittaya; Chomchey, Nitiya; Phanuphak, Praphan; Ananworanich, Jintanat] Thai Red Cross AIDS Res Ctr, Bangkok, Thailand. [Sandler, Netanya G.; Douek, Daniel C.] NIAID, Human Immunol Sect, Vaccine Res Ctr, NIH, Bethesda, MD 20892 USA. [Marovich, Mary; Robb, Merlin L.; Michael, Nelson L.; Excler, Jean-Louis; Kim, Jerome H.; Ananworanich, Jintanat] Walter Reed Army Inst Res, US Mil HIV Res Program, Silver Spring, MD USA. [Dewar, Robin] NCI, Virus Isolat & Serol Lab Appl & Dev Res Directora, Frederick Inc, Frederick Canc Res & Dev Ctr, Frederick, MD 21701 USA. RP Schuetz, A (reprint author), Armed Forces Res Inst Med Sci US Component, Dept Retrovirol, Bangkok, Thailand. EM schuetza@afrims.org OI Utay, Netanya/0000-0002-6407-8670 FU Henry M. Jackson Foundation for the Advancement of Military Medicine, Inc. [W81XWH-07-2-0067]; U.S. Department of Defense (DOD) [W81XWH-07-2-0067]; Thai Red Cross AIDS Research Center; UCLA CFAR grant [5P30 AI028697]; NIAID/NIH FX This work was supported by a cooperative agreement (W81XWH-07-2-0067) between the Henry M. Jackson Foundation for the Advancement of Military Medicine, Inc., and the U.S. Department of Defense (DOD) and by an intramural grant from the Thai Red Cross AIDS Research Center. Antiretroviral therapy was supported by the Thai Government Pharmaceutical Organization, Gilead, Merck and ViiV Healthcare. The UCLA CFAR Mucosal Immunology Core Laboratory is funded by UCLA CFAR grant 5P30 AI028697 and provided support and guidance regarding the isolation of MMC. The work of Irini Sereti was supported by Intramural Research Program of NIAID/NIH. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 79 TC 63 Z9 63 U1 0 U2 7 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 DEC PY 2014 VL 10 IS 12 AR e1004543 DI 10.1371/journal.ppat.1004543 PG 15 WC Microbiology; Parasitology; Virology SC Microbiology; Parasitology; Virology GA AX1JB UT WOS:000346702400030 PM 25503054 ER PT J AU Looy, CV Hotton, CL AF Looy, Cindy V. Hotton, Carol L. TI Spatiotemporal relationships among Late Pennsylvanian plant assemblages: Palynological evidence from the Markley Formation, West Texas, USA SO REVIEW OF PALAEOBOTANY AND PALYNOLOGY LA English DT Article DE Palaeoecology; Palynology; Environmental change; Pennsylvanian; Texas; Markley Formation ID PALEOZOIC ICE-AGE; NORTH-CENTRAL TEXAS; SEED FERN POLLEN; PERMIAN PALEOBOTANY; CLIMATE-CHANGE; FORMING ENVIRONMENTS; APPALACHIAN BASIN; MARATTIALEAN FERN; ATLANTIC CANADA; FOSSIL RECORD AB The Pennsylvanian lowlands of western Pangea are best known for their diverse wetland floras of arborescent and herbaceous ferns, and arborescent horsetails and clubmosses. In apparent juxtaposition, a very different kind of flora, dominated by a xerophilous assemblage of conifers, taeniopterids and peltasperms, is occasionally glimpsed. Once believed to represent upland or extrabasinal floras from well-drained portions of the landscape, these dryland floras more recently have been interpreted as lowland assemblages growing during drier phases of glacial/interglacial cycles. Whether Pennsylvanian dryland and wetland floras were separated spatially or temporally remains an unsettled question, due in large part to taphonomic bias toward preservation of wetland plants. Previous paleobotanical and sedimentological analysis of the Markley Formation of latest Pennsylvanian (Gzhelian) age, from north central Texas, U.S.A, indicates close correlation between lithofacies and distinct dryland and wetland megaflora assemblages. Here we present a detailed analysis one of those localities, a section unusual in containing abundant palynomorphs, from the lower Markley Formation. Paleobotanical, palynological and lithological data from a section thought to represent a single interglacial/glacial phase are integrated and analyzed to create a complex picture of an evolving landscape. Megafloral data from throughout the Markley Formation show that conifer-dominated dryland floras occur exclusively in highly leached kaolinite beds, likely eroded from underlying soils, whereas a mosaic of wetland floras occupy histosols, ultisols, and fluvial overbank deposits. Palynological data largely conform to this pattern but reveal a more complex picture. An assemblage of mixed wetland and dryland palynofloral taxa is interpolated between a dryland assemblage and an overlying histosol containing wetland taxa. In this section, as well as elsewhere in the Markley Formation, kaolinite and overlying organic beds appear to have formed as a single genetic unit, with the kaolinite forming an impermeable aquiclude upon which a poorly drained wetland subsequently formed. Within a single inferred glacial/interglacial cycle, lithological data indicate significant fluctuations in water availability tracked by changes in palynofloral and megafloral taxa. Palynology reveals that elements of the dryland floras appear at low abundance even within wetland deposits. The combined data indicate a complex pattern of succession and suggest a mosaic of dryland and wetland plant communities in the Late Pennsylvanian. Our data alone cannot show whether dryland and wetland assemblages succeed one another temporally, or coexisted on the landscape. However, the combined evidence suggests relatively close spatial proximity within a fragmenting and increasingly arid environment. (C) 2014 Elsevier B.V. All rights reserved. C1 [Looy, Cindy V.] Univ Calif Berkeley, Dept Integrat Biol, Berkeley, CA 94720 USA. [Looy, Cindy V.] Univ Calif Berkeley, Museum Paleontol, Berkeley, CA 94720 USA. [Hotton, Carol L.] NIH, Natl Ctr Biotechnol Informat, Natl Lib Med, Bethesda, MD 20892 USA. [Hotton, Carol L.] Smithsonian Inst, Natl Museum Nat Hist, Dept Paleobiol, Washington, DC 20560 USA. RP Looy, CV (reprint author), Univ Calif Berkeley, Dept Integrat Biol, 1005 Valley Life Sci Bldg 3140, Berkeley, CA 94720 USA. EM looy@berkeley.edu; hotton@ncbi.nlm.nih.gov FU Hellman Family Foundation; Intramural Research Program of the National Institutes of Health, National Library of Medicine FX We acknowledge William A. DiMichele for his generous sharing of samples and field notes, helpful discussions and support for this work. Ivo Duijnstee and Robert Stevenson assisted with imaging, figure and plate preparation. Critiques by Henk Visscher, Tom van Hoof and especially Hans Kerp greatly improved the manuscript. Cindy Looy was supported by the Hellman Family Foundation. The research of Carol Hotton was supported in part by the Intramural Research Program of the National Institutes of Health, National Library of Medicine. This is ETE publication 337, and UCMP Contribution 2055. NR 158 TC 2 Z9 2 U1 2 U2 85 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0034-6667 EI 1879-0615 J9 REV PALAEOBOT PALYNO JI Rev. Palaeobot. Palynology PD DEC PY 2014 VL 211 BP 10 EP 27 DI 10.1016/j.revpalbo.2014.09.007 PG 18 WC Plant Sciences; Paleontology SC Plant Sciences; Paleontology GA AX8BX UT WOS:000347136600002 PM 26028779 ER PT J AU Allen, JD Caspi, C Yang, M Leyva, B Stoddard, AM Tamers, S Tucker-Seeley, RD Sorensen, GC AF Allen, Jennifer Dacey Caspi, Caitlin Yang, May Leyva, Bryan Stoddard, Anne M. Tamers, Sara Tucker-Seeley, Reginald D. Sorensen, Glorian C. TI Pathways between acculturation and health behaviors among residents of low-income housing: The mediating role of social and contextual factors SO SOCIAL SCIENCE & MEDICINE LA English DT Article DE United States; Acculturation; Health behavior; Immigrant; Public housing; Social context ID FOOD FREQUENCY QUESTIONNAIRE; SELF-REPORTED SMOKING; UNITED-STATES; PHYSICAL-ACTIVITY; HISPANIC IMMIGRANTS; US HISPANICS; LIFE-COURSE; VALIDITY; DISCRIMINATION; MODEL AB Acculturation may influence health behaviors, yet mechanisms underlying its effect are not well understood. In this study, we describe relationships between acculturation and health behaviors among low-income housing residents, and examine whether these relationships are mediated by social and contextual factors. Residents of 20 low-income housing sites in the Boston metropolitan area completed surveys that assessed acculturative characteristics, social/contextual factors, and health behaviors. A composite acculturation scale was developed using latent class analysis, resulting in four distinct acculturative groups. Path analysis was used to examine interrelationships between acculturation, health behaviors, and social/contextual factors, specifically self-reported social ties, social support, stress, material hardship, and discrimination. Of the 828 respondents, 69% were born outside of the U.S. Less acculturated groups exhibited healthier dietary practices and were less likely to smoke than more acculturated groups. Acculturation had a direct effect on diet and smoking, but not physical activity. Acculturation also showed an indirect effect on diet through its relationship with material hardship. Our finding that material hardship mediated the relationship between acculturation and diet suggests the need to explicate the significant role of financial resources in interventions seeking to promote healthy diets among low-income immigrant groups. Future research should examine these social and contextual mediators using larger, population-based samples, preferably with longitudinal data. (C) 2014 The Authors. Published by Elsevier Ltd. C1 [Allen, Jennifer Dacey; Tamers, Sara; Tucker-Seeley, Reginald D.; Sorensen, Glorian C.] Dana Farber Canc Inst, Boston, MA 02215 USA. [Caspi, Caitlin] Univ Minnesota, Dept Family Med & Community Hlth, Minneapolis, MN 55455 USA. [Yang, May; Stoddard, Anne M.] New England Res Inst, Watertown, MA USA. [Leyva, Bryan] NCI, NIH, Bethesda, MD 20892 USA. RP Allen, JD (reprint author), Dana Farber Canc Inst, Phyllis Cantor Ctr Nursing Res & Patient Care Ser, Ctr Community Based Res, 450 Brookline Ave, Boston, MA 02215 USA. EM jennifer.allen@tufts.edu RI Allen, Jennifer/M-2113-2015 FU National Cancer Institute [R01 CA111310-01A1, K05 CA108663-05]; Centers for Disease Control and Prevention the NIH/NCI Harvard Education Program in Cancer Prevention and Control [U48DP001946, R25 CA057713]; NIH/NCI Cancer Related Health Disparities Education and Career Development Program [R25 CA163184]; NIH/NCI Reducing Social Disparities in Cancer Risk [K05 CA108663- 05]; NCI K01 career development award [CA169041-01] FX This research was supported by the National Cancer Institute (grant numbers R01 CA111310-01A1; K05 CA108663-05), Cooperative Agreement Number U48DP001946 from the Centers for Disease Control and Prevention the NIH/NCI Harvard Education Program in Cancer Prevention and Control (R25 CA057713), the NIH/NCI Cancer Related Health Disparities Education and Career Development Program (R25 CA163184), the NIH/NCI Reducing Social Disparities in Cancer Risk (K05 CA108663- 05), and an NCI K01 career development award (Grant# CA169041-01).The findings and conclusions in this journal article are those of the authors and do not necessarily represent the official position of the Centers for Disease Control and Prevention. The authors would like to thank the 20 low-income housing sites that participated in this research, and the assistance from the Cambridge, Somerville and Chelsea Public Housing Authorities. The authors also acknowledge the administrative and field staff at the Harvard School of Public Health and Dana-Farber Cancer Institute, and the study participants for their contributions to this project. They also thank Gary Adamkiewicz, Marty Alvarez-Reeves, Amy Harley, Ruth Lederman, Samuel Lipson, Carol Lowenstein, Hannah L Mills, Laura Tom, Brianna Wadler, and Lorraine Wallace for their contributions to the overall study design and implementation. NR 69 TC 10 Z9 10 U1 8 U2 31 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 DEC PY 2014 VL 123 BP 26 EP 36 DI 10.1016/j.socscimed.2014.10.034 PG 11 WC Public, Environmental & Occupational Health; Social Sciences, Biomedical SC Public, Environmental & Occupational Health; Biomedical Social Sciences GA AX6GT UT WOS:000347021800004 PM 25462602 ER PT J AU Chen, L Mathema, B Chavda, KD DeLeo, FR Bonomo, RA Kreiswirth, BN AF Chen, Liang Mathema, Barun Chavda, Kalyan D. DeLeo, Frank R. Bonomo, Robert A. Kreiswirth, Barry N. TI Carbapenemase-producing Klebsiella pneumoniae: molecular and genetic decoding SO TRENDS IN MICROBIOLOGY LA English DT Review DE Klebsiella pneumoniae carbapenemase; carbapenem-resistant; ST258 ID SEQUENCE TYPE 258; COMPLETE NUCLEOTIDE-SEQUENCE; COMPLETE GENOME SEQUENCE; NEW-YORK HOSPITALS; HYDROLYZING BETA-LACTAMASE; NEW-JERSEY; PSEUDOMONAS-AERUGINOSA; ANTIBIOTIC-RESISTANCE; BLA(KPC) GENE; 1ST DESCRIPTION AB Klebsiella pneumoniae carbapenemases (KPCs) were first identified in 1996 in the USA. Since then, regional outbreaks of KPC-producing K. pneumoniae (KPC-Kp) have occurred in the USA, and have spread internationally. Dissemination of bla(KPC) involves both horizontal transfer of bla(KPC) genes and plasmids, and clonal spread. Of epidemiological significance, the international spread of KPC-producing K. pneumoniae is primarily associated with a single multilocus sequence type (ST), ST258, and its related variants. However, the molecular factors contributing to the success of ST258 largely remain unclear. In this review, we discuss the recent progresses in understanding KPC-producing K. pneumoniae that are contributing to our knowledge of plasmid and genome composition and structure among the KPC epidemic clone, and we identify possible factors that influence its epidemiological success. C1 [Chen, Liang; Mathema, Barun; Chavda, Kalyan D.; Kreiswirth, Barry N.] Rutgers State Univ, New Jersey Med Sch, Publ Res Inst, TB Ctr, Newark, NJ 07103 USA. [Mathema, Barun] Columbia Univ, Dept Epidemiol, Mailman Sch Publ Hlth, New York, NY 10032 USA. [DeLeo, Frank R.] NIAID, Lab Human Bacterial Pathogenesis, Rocky Mt Labs, NIH, Hamilton, MT 59840 USA. [Bonomo, Robert A.] Vet Affairs Med Ctr, Louis Stokes Cleveland Dept, Res Serv, Cleveland, OH 44106 USA. [Bonomo, Robert A.] Case Western Reserve Univ, Dept Med, Cleveland, OH 44106 USA. [Bonomo, Robert A.] Case Western Reserve Univ, Dept Pharmacol, Cleveland, OH 44106 USA. [Bonomo, Robert A.] Case Western Reserve Univ, Dept Mol Biol & Microbiol, Cleveland, OH 44106 USA. RP Kreiswirth, BN (reprint author), Rutgers State Univ, New Jersey Med Sch, Publ Res Inst, TB Ctr, Newark, NJ 07103 USA. EM kreiswba@njms.rutgers.edu OI DeLeo, Frank/0000-0003-3150-2516 FU National Institutes of Health (NIH) [1R01AI090155]; Intramural Research Program of the NIAID, NIH; Public Health Service [R01AI072219, R01AI063517]; Cleveland Department of Veterans Affairs; Veterans Affairs Merit Review Program; Geriatric Research Education and Clinical Center [VISN 10] FX This work was supported in part by National Institutes of Health (NIH) Grant 1R01AI090155 (to B.N.K.), and by the Intramural Research Program of the NIAID, NIH. This work was also supported by Public Health Service grant R01AI072219 and R01AI063517 (to R.A. Bonomo) from the National Institutes of Health and funds and/or facilities provided by the Cleveland Department of Veterans Affairs, the Veterans Affairs Merit Review Program and the Geriatric Research Education and Clinical Center VISN 10 to R. A. Bonomo. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institute of Health. NR 80 TC 47 Z9 52 U1 5 U2 24 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0966-842X EI 1878-4380 J9 TRENDS MICROBIOL JI Trends Microbiol. PD DEC PY 2014 VL 22 IS 12 BP 686 EP 696 DI 10.1016/j.tim.2014.09.003 PG 11 WC Biochemistry & Molecular Biology; Microbiology SC Biochemistry & Molecular Biology; Microbiology GA AX8CF UT WOS:000347137400006 PM 25304194 ER PT J AU Safdar, B Greenberg, MR Anise, A Brown, J Conwit, R Filart, R Scott, J Choo, EK AF Safdar, Basmah Greenberg, Marna R. Anise, Ayodola Brown, Jeremy Conwit, Robin Filart, Rosemarie Scott, Jane Choo, Esther K. TI Funding Mechanisms for Gender-specific Research: Proceedings from a Panel Discussion at the 2014 Academic Emergency Medicine Consensus Conference SO ACADEMIC EMERGENCY MEDICINE LA English DT Article AB As part of the 2014 Academic Emergency Medicine (AEM) consensus conference Gender-Specific Research in Emergency Care: Investigate, Understand, and Translate How Gender Affects Patient Outcomes, we assembled a diverse panel of representatives from federal and nonfederal funding agencies to discuss future opportunities for sex- and gender-specific research. The discussion revolved around the mission and priorities of each organization, as well as its interest in promoting sex- and gender-specific research. The panelists were asked to provide specific examples of funding lines generated or planned for as pertinent to emergency care. Training opportunities for future researchers in this area were also discussed. C1 [Safdar, Basmah] Yale Univ, Dept Emergency Med, New Haven, CT 06520 USA. [Greenberg, Marna R.] Lehigh Valley Hlth Networks, Dept Emergency Med, Allentown, PA USA. [Anise, Ayodola] Patient Ctr Outcome Res Inst, Addressing Dispar Program, Washington, DC USA. [Brown, Jeremy] NIH, Off Emergency Care Res, Bethesda, MD 20892 USA. [Conwit, Robin] NINDS, Off Clin Res, Bethesda, MD 20892 USA. [Filart, Rosemarie] NIH, Off Res Womens Hlth, Bethesda, MD 20892 USA. [Scott, Jane] NHLBI, DCVS, NIH, Bethesda, MD 20892 USA. [Choo, Esther K.] Brown Univ, Dept Emergency Med, Providence, RI 02912 USA. RP Safdar, B (reprint author), Yale Univ, Dept Emergency Med, New Haven, CT 06520 USA. EM basmah.safdar@yale.edu FU National Institute of Neurological Disorders and Stroke [1R13NS087861-01]; Office of Research on Women's Health at the NIH FX The consensus conference was supported by grant 1R13NS087861-01 from the National Institute of Neurological Disorders and Stroke and the Office of Research on Women's Health at the NIH. Additional funding was provided by several organizational, institutional, and individual donors. Non-CME events were supported by Janssen Pharmaceuticals and Besins Critical Care/BH Pharma. See the Executive Summary elsewhere in this issue for full funding information. NR 8 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1069-6563 EI 1553-2712 J9 ACAD EMERG MED JI Acad. Emerg. Med. PD DEC PY 2014 VL 21 IS 12 BP 1329 EP 1333 DI 10.1111/acem.12522 PG 5 WC Emergency Medicine SC Emergency Medicine GA AW9KS UT WOS:000346576700005 PM 25413301 ER PT J AU Safdar, B Nagurney, JT Anise, A DeVon, HA D'Onofrio, G Hess, EP Hollander, JE Legato, MJ McGregor, AJ Scott, J Tewelde, S Diercks, DB AF Safdar, Basmah Nagurney, John T. Anise, Ayodola DeVon, Holli A. D'Onofrio, Gail Hess, Erik P. Hollander, Judd E. Legato, Mariane J. McGregor, Alyson J. Scott, Jane Tewelde, Semhar Diercks, Deborah B. TI Gender-specific Research for Emergency Diagnosis and Management of Ischemic Heart Disease: Proceedings from the 2014 Academic Emergency Medicine Consensus Conference Cardiovascular Research Workgroup SO ACADEMIC EMERGENCY MEDICINE LA English DT Article ID CORONARY-ARTERY-DISEASE; SYNDROME EVALUATION WISE; QUANTITATIVE PRETEST PROBABILITY; ELEVATION MYOCARDIAL-INFARCTION; TAKO-TSUBO CARDIOMYOPATHY; ACUTE CHEST-PAIN; DEPARTMENT PATIENTS; ANGINA-PECTORIS; SEX-DIFFERENCES; TAKOTSUBO CARDIOMYOPATHY AB Coronary artery disease (CAD) is the most common cause of death for both men and women. However, over the years, emergency physicians, cardiologists, and other health care practitioners have observed varying outcomes in men and women with symptomatic CAD. Women in general are 10 to 15 years older than men when they develop CAD, but suffer worse postinfarction outcomes compared to age-matched men. This article was developed by the cardiovascular workgroup at the 2014 Academic Emergency Medicine (AEM) consensus conference to identify sex- and gender-specific gaps in the key themes and research questions related to emergency cardiac ischemia care. The workgroup had diverse stakeholder representation from emergency medicine, cardiology, critical care, nursing, emergency medical services, patients, and major policy-makers in government, academia, and patient care. We implemented the nominal group technique to identify and prioritize themes and research questions using electronic mail, monthly conference calls, in-person meetings, and Web-based surveys between June 2013 and May 2014. Through three rounds of nomination and refinement, followed by an in-person meeting on May 13, 2014, we achieved consensus on five priority themes and 30 research questions. The overarching themes were as follows: 1) the full spectrum of sex-specific risk as well as presentation of cardiac ischemia may not be captured by our standard definition of CAD and needs to incorporate other forms of ischemic heart disease (IHD); 2) diagnosis is further challenged by sex/gender differences in presentation and variable sensitivity of cardiac biomarkers, imaging, and risk scores; 3) sex-specific pathophysiology of cardiac ischemia extends beyond conventional obstructive CAD to include other causes such as microvascular dysfunction, takotsubo, and coronary artery dissection, better recognized as IHD; 4) treatment and prognosis are influenced by sex-specific variations in biology, as well as patient-provider communication; and 5) the changing definitions of pathophysiology call for looking beyond conventionally defined cardiovascular outcomes to patient-centered outcomes. These emergency care priorities should guide future clinical and basic science research and extramural funding in an area that greatly influences patient outcomes. C1 [Safdar, Basmah; D'Onofrio, Gail] Yale Univ, Dept Emergency Med, New Haven, CT 06520 USA. [Nagurney, John T.] Massachusetts Gen Hosp, Dept Emergency Med, Boston, MA 02114 USA. [Hess, Erik P.] Mayo Clin, Dept Emergency Med, Rochester, MN USA. Thomas Jefferson Univ, Dept Emergency Med, Sidney Kimmel Med Coll, Philadelphia, PA 19107 USA. [McGregor, Alyson J.] Brown Univ, Dept Emergency Med, Warren Alpert Med Sch, Providence, RI 02912 USA. [Tewelde, Semhar] Univ Maryland, Dept Emergency Med, College Pk, MD 20742 USA. [Diercks, Deborah B.] Univ Calif Davis, Med Ctr, Dept Emergency Med, Davis, CA 95616 USA. [Anise, Ayodola] Patient Ctr Outcomes Res Inst, Washington, DC USA. [DeVon, Holli A.] Univ Illinois, Coll Nursing, Chicago, IL USA. [Legato, Mariane J.] Columbia Univ, Cardiol Sect, Dept Med, New York, NY USA. [Scott, Jane] NHLBI, Washington, DC USA. RP Safdar, B (reprint author), Yale Univ, Dept Emergency Med, New Haven, CT 06520 USA. EM basmah.safdar@yale.edu OI Hollander, Judd/0000-0002-1318-2785; D'Onofrio, Gail/0000-0002-3833-1871 FU National Institute of Neurological Disorders and Stroke [1R13NS087861-01]; Office of Research on Women's Health at the National Institutes of Health FX The consensus conference was supported by grant 1R13NS087861-01 from the National Institute of Neurological Disorders and Stroke and the Office of Research on Women's Health at the National Institutes of Health. Additional funding was provided by several organizational, institutional, and individual donors. Non-CME events were supported by Janssen Pharmaceuticals and Besins Critical Care/BH Pharma. See the executive summary elsewhere in this issue for full funding information. NR 76 TC 4 Z9 5 U1 3 U2 13 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1069-6563 EI 1553-2712 J9 ACAD EMERG MED JI Acad. Emerg. Med. PD DEC PY 2014 VL 21 IS 12 BP 1350 EP 1360 DI 10.1111/acem.12527 PG 11 WC Emergency Medicine SC Emergency Medicine GA AW9KS UT WOS:000346576700009 PM 25413468 ER PT J AU Wager, TT Chandrasekaran, RY Bradley, J Rubitski, D Berke, H Mente, S Butler, T Doran, A Chang, C Fisher, K Knafels, J Liu, SP Ohren, J Marconi, M DeMarco, G Sneed, B Walton, K Horton, D Rosado, A Mead, A AF Wager, Travis T. Chandrasekaran, Ramalakshmi Y. Bradley, Jenifer Rubitski, David Berke, Helen Mente, Scot Butler, Todd Doran, Angela Chang, Cheng Fisher, Katherine Knafels, John Liu, Shenping Ohren, Jeff Marconi, Michael DeMarco, George Sneed, Blossom Walton, Kevin Horton, David Rosado, Amy Mead, Andy TI Casein Kinase 1 delta/epsilon Inhibitor PF-5006739 Attenuates Opioid Drug-Seeking Behavior SO ACS CHEMICAL NEUROSCIENCE LA English DT Article DE Casein kinase 1; CK1 delta; CK1 epsilon; PF-5006739; dual inhibitor; circadian rhythm; phase-delaying; opioid reinstatement; drug addiction ID CENTRAL-NERVOUS-SYSTEM; SLEEP-PHASE SYNDROME; CIRCADIAN CLOCK; DARPP-32; MUTATION; RECEPTOR; DETERMINANTS; ADDICTION; ALIGNMENT; EPSILON AB Casein kinase 1 delta (CK1 delta) and casein kinase 1 epsilon (CK1 epsilon) inhibitors are potential therapeutic agents for a range of psychiatric disorders. The feasibility of developing a CNS kinase inhibitor has been limited by an inability to identify safe brain-penetrant compounds with high kinome selectivity. Guided by structure-based drug design, potent and selective CK1 delta/epsilon inhibitors have now been identified that address this gap, through the design and synthesis of novel 4-[4-(4-fluoropheny1)-1-(piperidin-4-yl)-1H-imidazol-5-yl]pyrimidin-2-amine derivatives. PF-5006739 (6) possesses a desirable profile, with low nanomolar in vitro potency for CK1 delta/epsilon (IC50 = 3.9 and 17.0 nM, respectively) and high kinome selectivity. In vivo, 6 demonstrated robust centrally mediated circadian rhythm phase-delaying effects in both nocturnal and diurnal animal models. Further, 6 dose-dependently attenuated opioid drug-seeking behavior in a rodent operant reinstatement model in animals trained to self-administer fentanyl. Collectively, our data supports further development of 6 as a promising candidate to test the hypothesis of CK1 delta/epsilon inhibition in treating multiple indications in the clinic. C1 [Wager, Travis T.; Rubitski, David; Mente, Scot; Fisher, Katherine; Marconi, Michael; DeMarco, George] Pfizer Worldwide Res & Dev, Cambridge, MA 02139 USA. [Chandrasekaran, Ramalakshmi Y.; Bradley, Jenifer; Berke, Helen; Butler, Todd; Doran, Angela; Chang, Cheng; Knafels, John; Liu, Shenping; Ohren, Jeff; Sneed, Blossom; Horton, David; Rosado, Amy; Mead, Andy] Pfizer Worldwide Res & Dev, Groton, CT 06340 USA. [Walton, Kevin] NIAID, Div Pharmacotherapies & Med Consequences Drug Abu, NIH, Rockville, MD 20852 USA. RP Wager, TT (reprint author), Pfizer Worldwide Res & Dev, 610 Main St, Cambridge, MA 02139 USA. EM travis.t.wager@pfizer.com NR 37 TC 4 Z9 4 U1 0 U2 3 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 DEC PY 2014 VL 5 IS 12 BP 1253 EP 1265 DI 10.1021/cn500201x PG 13 WC Biochemistry & Molecular Biology; Chemistry, Medicinal; Neurosciences SC Biochemistry & Molecular Biology; Pharmacology & Pharmacy; Neurosciences & Neurology GA AX1AY UT WOS:000346682000015 PM 25299732 ER PT J AU Elias, AF AF Elias, Abdallah F. TI The Shodair Medical Genetics Department-Recent Past and Future Developments SO AMERICAN JOURNAL OF MEDICAL GENETICS PART C-SEMINARS IN MEDICAL GENETICS LA English DT Article DE Shodair Hospital; Philip Pallister; medical genetics ID DELETION; MUTATIONS AB Philip Pallister and John Opitz laid the ground work for a unique genetic service model in Montana that continues to flourish through ongoing support by the Montana Legislature, the Montana Department of Public Health and Human Services and the Shodair Foundation. At the heart of the model are clinical and laboratory genetic specialists based at Shodair Children's Hospital in Helena providing genetic care for patients through outreach clinics. Clinical services are supported by a state-of-the-art cytogenetics and molecular genetic laboratory as well a fetal genetic pathology program. Over the years, the reach of regular genetics clinics expanded to include large geographic areas including northwest (Kalispell), west central (Missoula), southwest (Bozeman, Butte), north central (Great Falls), and south central Montana (Billings). Building on the foundation of its world-renowned pioneers, the next generation of medical geneticists at Shodair carries the responsibility of integrating genomic medicine in the diagnosis and care of their patients, reducing inequality of services within Montana and partnering with colleagues across specialties to develop a more personalized practice of medicine. (c) 2014 Wiley Periodicals, Inc. C1 [Elias, Abdallah F.] Shodair Childrens Hosp, Helena, MT 59601 USA. [Elias, Abdallah F.] Johns Hopkins Univ, Sch Med, McKusick Nathans Inst Genet Med, Baltimore, MD 21218 USA. [Elias, Abdallah F.] Univ Montana, Dept Biomed & Pharmaceut Sci, Missoula, MT 59812 USA. [Elias, Abdallah F.] Western Montana Family Med Residency Program, Missoula, MT USA. [Elias, Abdallah F.] NIAID, Rocky Mt Labs, NIH, Bethesda, MD USA. RP Elias, AF (reprint author), Shodair Childrens Hosp, Dept Med Genet, 2755 Colonial Dr, Helena, MT 59601 USA. EM aelias@shodair.org NR 10 TC 0 Z9 0 U1 1 U2 2 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1552-4868 EI 1552-4876 J9 AM J MED GENET C JI Am. J. Med. Genet. C PD DEC PY 2014 VL 166 IS 4 BP 381 EP 386 DI 10.1002/ajmg.c.31417 PG 6 WC Genetics & Heredity SC Genetics & Heredity GA AX1HW UT WOS:000346699300003 PM 25424535 ER PT J AU Kobayashi, H Turkbey, B Watanabe, R Choyke, PL AF Kobayashi, Hisataka Turkbey, Baris Watanabe, Rira Choyke, Peter L. TI Cancer Drug Delivery: Considerations in the Rational Design of Nanosized Bioconjugates SO BIOCONJUGATE CHEMISTRY LA English DT Review ID TRANSCAPILLARY PRESSURE-GRADIENT; HUMAN OSTEOSARCOMA XENOGRAFTS; GROWTH-FACTOR VEGF; SOLID TUMORS; IN-VIVO; ENHANCED PERMEABILITY; LIPOSOMAL DOXORUBICIN; VASCULAR-PERMEABILITY; BLOOD-VESSELS; SIZE AB In order to efficiently deliver anticancer agents to tumors, biocompatible nanoparticles or bioconjugates, including antibody-drug conjugates (ADCs), have recently been designed, synthesized, and tested, some even in clinical trials. Controlled delivery can be enhanced by changing specific design characteristics of the bioconjugate such as its size, the nature of the payload, and the surface features. The delivery of macromolecular drugs to cancers largely relies on the leaky nature of the tumor vasculature compared with healthy vessels in normal organs. When administered intravenously, macromolecular bioconjugates and nanosized agents tend to circulate for prolonged times, unless they are small enough to be excreted by the kidney or stealthy enough to evade the macrophage phagocytic system (MPS), formerly the reticulo-endothelial system (RES). Therefore, macromolecular bioconjugates and nanosized agents with long circulation times leak preferentially into tumor tissue through permeable tumor vessels and are then retained in the tumor bed due to reduced lymphatic drainage. This process is known as the enhanced permeability and retention (EPR) effect. However, success of cancer drug delivery only relying on the EPR effect is still limited. To cure cancer patients, further improvement of drug delivery is required by both designing superior agents and enhancing EPR effects. In this Review, we describe the basis of macromolecular or nanosized bioconjugate delivery into cancer tissue and discuss current diagnostic methods for evaluating leakiness of the tumor vasculature. Then, we discuss methods to augment conventional "permeability and retention" effects for macromolecular or nanosized bioconjugates in cancer tissue. C1 [Kobayashi, Hisataka; Turkbey, Baris; Watanabe, Rira; Choyke, Peter L.] NCI, Mol Imaging Program, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. RP Kobayashi, H (reprint author), NCI, Mol Imaging Program, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. EM Kobayash@mail.nih.gov FU Intramural Research Program of the 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 75 TC 16 Z9 16 U1 8 U2 47 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 1043-1802 J9 BIOCONJUGATE CHEM JI Bioconjugate Chem. PD DEC PY 2014 VL 25 IS 12 BP 2093 EP 2100 DI 10.1021/bc500481x PG 8 WC Biochemical Research Methods; Biochemistry & Molecular Biology; Chemistry, Multidisciplinary; Chemistry, Organic SC Biochemistry & Molecular Biology; Chemistry GA AX1BB UT WOS:000346682300001 PM 25385142 ER PT J AU Huynh, D Laeyendecker, O Brookmeyer, R AF Huynh, Dat Laeyendecker, Oliver Brookmeyer, Ron TI A Serial Risk Score Approach to Disease Classification that Accounts for Accuracy and Cost SO BIOMETRICS LA English DT Article DE Biomarkers; Classification; Diagnostic tests; HIV ID HIV-INFECTION; BIOMARKERS; COHORT; ERROR AB The performance of diagnostic tests for disease classification is often measured by accuracy (e.g., sensitivity or specificity); however, costs of the diagnostic test are a concern as well. Combinations of multiple diagnostic tests may improve accuracy, but incur additional costs. Here, we consider serial testing approaches that maintain accuracy while controlling costs of the diagnostic tests. We present a serial risk score classification approach. The basic idea is to sequentially test with additional diagnostic tests just until persons are classified. In this way, it is not necessary to test all persons with all tests. The methods are studied in simulations and compared with logistic regression. We applied the methods to data from HIV cohort studies to identify HIV infected individuals who are recently infected (<1 year) by testing with assays for multiple biomarkers. We find that the serial risk score classification approach can maintain accuracy while achieving a reduction in cost compared to testing all individuals with all assays. C1 [Huynh, Dat; Brookmeyer, Ron] Univ Calif Los Angeles, Dept Biostat, Los Angeles, CA 90095 USA. [Laeyendecker, Oliver] Johns Hopkins Univ, Sch Med, Dept Med, NIAID,NIH, Baltimore, MD 21205 USA. RP Brookmeyer, R (reprint author), Univ Calif Los Angeles, Dept Biostat, Los Angeles, CA 90095 USA. EM rbrookmeyer@ucla.edu OI Laeyendecker, Oliver/0000-0002-6429-4760 FU National Institutes of Health [R01-AI095068]; Division of Intramural Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health; HIVNET; NIAID; NIDA; NIAIDNational Cancer Institute; National Heart, Lung, and Blood Institute FX This work was supported by National Institutes of Health grant R01-AI095068 and in part by the Division of Intramural Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health.; The HIV Network for Prevention Trials (HIVNET) 001 Study was funded by the HIVNET and sponsored by the NIAID; the AIDS Link to Intravenous Experience (ALIVE) Study was funded by the NIDA; and the Multicenter AIDS Cohort Study (MACS) was funded by the NIAID, with additional supplemental funding from the National Cancer Institute and National Heart, Lung, and Blood Institute. NR 21 TC 1 Z9 1 U1 1 U2 1 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0006-341X EI 1541-0420 J9 BIOMETRICS JI Biometrics PD DEC PY 2014 VL 70 IS 4 BP 1042 EP 1051 DI 10.1111/biom.12217 PG 10 WC Biology; Mathematical & Computational Biology; Statistics & Probability SC Life Sciences & Biomedicine - Other Topics; Mathematical & Computational Biology; Mathematics GA AX3GF UT WOS:000346827500028 PM 25156309 ER PT J AU McLain, AC Albert, PS AF McLain, Alexander C. Albert, Paul S. TI Modeling Longitudinal Data with a Random Change Point and No Time-Zero: Applications to Inference and Prediction of the Labor Curve SO BIOMETRICS LA English DT Article DE Change point; Heterogeneity; Longitudinal analysis; Prediction ID MIXED-EFFECTS MODEL AB In some longitudinal studies the initiation time of the process is not clearly defined, yet it is important to make inference or do predictions about the longitudinal process. The application of interest in this article is to provide a framework for modeling individualized labor curves (longitudinal cervical dilation measurements) where the start of labor is not clearly defined. This is a well-known problem in obstetrics where the benchmark reference time is often chosen as the end of the process (individuals are fully dilated at 10cm) and time is run backwards. This approach results in valid and efficient inference unless subjects are censored before the end of the process, or if we are focused on prediction. Providing dynamic individualized predictions of the longitudinal labor curve prospectively (where backwards time is unknown) is of interest to aid obstetricians to determine if a labor is on a suitable trajectory. We propose a model for longitudinal labor dilation that uses a random-effects model with unknown time-zero and a random change point. We present a maximum likelihood approach for parameter estimation that uses adaptive Gaussian quadrature for the numerical integration. Further, we propose a Monte Carlo approach for dynamic prediction of the future longitudinal dilation trajectory from past dilation measurements. The methodology is illustrated with longitudinal cervical dilation data from the Consortium of Safe Labor Study. C1 [McLain, Alexander C.] Univ S Carolina, Dept Epidemiol & Biostat, Columbia, SC 29208 USA. [Albert, Paul S.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Biostat & Bioinformat Branch, Div Intramural Populat Hlth Res, NIH,DHHS, Rockville, MD 20852 USA. RP McLain, AC (reprint author), Univ S Carolina, Dept Epidemiol & Biostat, 800 Sumter St, Columbia, SC 29208 USA. EM mclaina@mailbox.sc.edu FU Intramural Research Program of the National Institutes of Health Eunice Kennedy Shriver National Institute of Child Health and Human Development; Division of Intramural Population Health Research, Eunice Kennedy Shriver National Institute of Child Health and Human Development FX We thank the editor, associate editor, and referee for their helpful comments. This study utilized the high-performance computational capabilities of the Biowulf Linux cluster at the National Institutes of Health, Bethesda, MD (http://biowulf.nih.gov). The research of Paul Albert was supported by the Intramural Research Program of the National Institutes of Health Eunice Kennedy Shriver National Institute of Child Health and Human Development. The research by Alexander McLain was supported, in part, by an Interpersonal Agreement with the Division of Intramural Population Health Research, Eunice Kennedy Shriver National Institute of Child Health and Human Development. NR 16 TC 1 Z9 1 U1 2 U2 7 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0006-341X EI 1541-0420 J9 BIOMETRICS JI Biometrics PD DEC PY 2014 VL 70 IS 4 BP 1052 EP 1060 DI 10.1111/biom.12218 PG 9 WC Biology; Mathematical & Computational Biology; Statistics & Probability SC Life Sciences & Biomedicine - Other Topics; Mathematical & Computational Biology; Mathematics GA AX3GF UT WOS:000346827500029 PM 25156417 ER PT J AU Johnson, JO Glynn, SM Gibbs, R Nalls, MA Sabatelli, M Restagno, G Drory, VE Chio, A Rogaeva, E Traynor, BJ AF Johnson, Janel O. Glynn, Shannon M. Gibbs, Raphael Nalls, Mike A. Sabatelli, Mario Restagno, Gabriella Drory, Vivian E. Chio, Adriano Rogaeva, Ekaterina Traynor, Bryan J. TI Mutations in the CHCHD10 gene are a common cause of familial amyotrophic lateral sclerosis SO BRAIN LA English DT Letter C1 [Johnson, Janel O.; Glynn, Shannon M.; Traynor, Bryan J.] NIA, Neuromuscular Dis Res Sect, Neurogenet Lab, Bethesda, MD 20892 USA. [Gibbs, Raphael] NIA, Computat Biol Core, Neurogenet Lab, Bethesda, MD 20892 USA. [Nalls, Mike A.] NIA, Mol Genet Sect, Neurogenet Lab, Bethesda, MD 20892 USA. [Sabatelli, Mario] Univ Cattolica Sacro Cuore, Neurol Inst, I-00168 Rome, Italy. [Sabatelli, Mario] Insieme Contro Malattie Motoneurone Assoc ALS Res, I-00168 Rome, Italy. [Restagno, Gabriella] Azienda Sanit Osped Osped Infantile Reg Margher S, Dept Clin Pathol, Mol Genet Unit, I-10126 Turin, Italy. [Drory, Vivian E.] Sourasky Med Ctr, Dept Neurol, IL-64239 Tel Aviv, Israel. [Chio, Adriano] Univ Turin, Rita Levi Montalcini Dept Neurosci, I-10124 Turin, Italy. [Rogaeva, Ekaterina] Univ Toronto, Div Neurol, Dept Med, Tanz Ctr Res Neurodegenerat Dis, Toronto, ON M5S 3H2, Canada. RP Traynor, BJ (reprint author), NIA, Neurogenet Lab, NIH, 35 Convent Dr, Bethesda, MD 20892 USA. EM traynorb@mail.nih.gov OI Sabatelli, Mario/0000-0001-6635-4985; Chio, Adriano/0000-0001-9579-5341 FU Intramural NIH HHS; NIA NIH HHS [Z01-AG000949-02] NR 5 TC 34 Z9 34 U1 2 U2 8 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0006-8950 EI 1460-2156 J9 BRAIN JI Brain PD DEC PY 2014 VL 137 AR e311 DI 10.1093/brain/awu265 PN 12 PG 2 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA AX2GJ UT WOS:000346761200003 PM 25261972 ER PT J AU Chen, LY Brown, PR Willis, WB Eddy, EM AF Chen, Liang-Yu Brown, Paula R. Willis, William B. Eddy, Edward M. TI Peritubular Myoid Cells Participate in Male Mouse Spermatogonial Stem Cell Maintenance SO ENDOCRINOLOGY LA English DT Article ID NEUROTROPHIC FACTOR; SERTOLI-CELLS; SEMINIFEROUS TUBULES; ANDROGEN RECEPTOR; GENE-EXPRESSION; GROWTH-FACTOR; SELF-RENEWAL; RAT TESTIS; IMMUNOHISTOCHEMICAL LOCALIZATION; UNDIFFERENTIATED SPERMATOGONIA AB Peritubular myoid (PM) cells surround the seminiferous tubule and together with Sertoli cells form the cellular boundary of the spermatogonial stem cell (SSC) niche. However, it remains unclear what role PM cells have in determining the microenvironment in the niche required for maintenance of the ability of SSCs to undergo self-renewal and differentiation into spermatogonia. Mice with a targeted disruption of the androgen receptorgene(Ar) in PM cells experienced a progressive loss of spermatogonia, suggesting that PM cells require testosterone (T) action to produce factors influencing SSC maintenance in the niche. Other studies showed that glial cell line-derived neurotrophic factor (GDNF) is required for SSC self-renewal and differentiation of SSCs in vitro and in vivo. This led us to hypothesize that T-regulated GDNF expression by PM cells contributes to the maintenance of SSCs. This hypothesis was tested using an adult mouse PM cell primary culture system and germ cell transplantation. We found that T induced GDNF expression at the mRNA and protein levels in PM cells. Furthermore, when thymus cell antigen 1-positive spermatogonia isolated from neonatal mice were cocultured with PM cells with or without T and transplanted to the testes of germ cell-depleted mice, the number and length of transplant-derived colonies was increased considerably by in vitro T treatment. These results support the novel hypothesis that T-dependent regulation of GDNF expression in PM cells has a significant influence on the microenvironment of the niche and SSC maintenance. C1 [Chen, Liang-Yu; Willis, William B.; Eddy, Edward M.] NIEHS, Gamete Biol Grp, Lab Reprod & Dev Toxicol, NIH, Res Triangle Pk, NC 27709 USA. [Brown, Paula R.] NIEHS, Reprod Dev Biol Grp, Lab Reprod & Dev Toxicol, NIH, Res Triangle Pk, NC 27709 USA. RP Eddy, EM (reprint author), NIEHS, Reprod & Dev Toxicol Lab, NIH, 111 TW Alexander Dr, Res Triangle Pk, NC 27709 USA. EM eddy@niehs.nih.gov FU Intramural Research Program of the National Institutes of Health, National Institute of Environmental Health Sciences FX This work was supported by the Intramural Research Program of the National Institutes of Health, National Institute of Environmental Health Sciences. NR 70 TC 15 Z9 16 U1 1 U2 9 PU ENDOCRINE SOC PI WASHINGTON PA 2055 L ST NW, SUITE 600, WASHINGTON, DC 20036 USA SN 0013-7227 EI 1945-7170 J9 ENDOCRINOLOGY JI Endocrinology PD DEC PY 2014 VL 155 IS 12 BP 4964 EP 4974 DI 10.1210/en.2014-1406 PG 11 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA AX0UN UT WOS:000346668000034 PM 25181385 ER PT J AU Tamaresis, JS Irwin, JC Goldfien, GA Rabban, JT Burney, RO Nezhat, C DePaolo, LV Giudice, LC AF Tamaresis, John S. Irwin, Juan C. Goldfien, Gabriel A. Rabban, Joseph T. Burney, Richard O. Nezhat, Camran DePaolo, Louis V. Giudice, Linda C. TI Molecular Classification of Endometriosis and Disease Stage Using High-Dimensional Genomic Data SO ENDOCRINOLOGY LA English DT Article ID QUALITY-OF-LIFE; GENE-EXPRESSION; EUTOPIC ENDOMETRIUM; MILD ENDOMETRIOSIS; WOMEN; BIOMARKERS; MICROARRAY; DIAGNOSIS; PATHWAYS; FOS AB Endometriosis (E), an estrogen-dependent, progesterone-resistant, inflammatory disorder, affects 10% of reproductive-age women. It is diagnosed and staged at surgery, resulting in an 11-year latency from symptom onset to diagnosis, underscoring the need for less invasive, less expensive approaches. Because the uterine lining (endometrium) in women with E has altered molecular profiles, we tested whether molecular classification of this tissue can distinguish and stage disease. We developed classifiers using genomic data from n = 148 archived endometrial samples from women with E or without E (normal controls or with other common uterine/pelvic pathologies) across the menstrual cycle and evaluated their performance on independent sample sets. Classifiers were trained separately on samples in specific hormonal milieu, using margin tree classification, and accuracies were scored on independent validation samples. Classification of samples from women with E or no E involved 2 binary decisions, each based on expression of specific genes. These first distinguished presence or absence of uterine/pelvic pathology and then no E from E, with the latter further classified according to severity (minimal/mild or moderate/severe). Best performing classifiers identified E with 90%-100% accuracy, were cycle phase-specific or independent, and used relatively few genes to determine disease and severity. Differential gene expression and pathway analyses revealed immune activation, altered steroid and thyroid hormone signaling/metabolism, and growth factor signaling in endometrium of women with E. Similar findings were observed with other disorders vs controls. Thus, classifier analysis of genomic data from endometrium can detect and stage pelvic E with high accuracy, dependent or independent of hormonal milieu. We propose that limited classifier candidate genes are of high value in developing diagnostics and identifying therapeutic targets. Discovery of endometrial molecular differences in the presence of E and other uterine/pelvic pathologies raises the broader biological question of their impact on the steroid hormone response and normal functions of this tissue. C1 [Tamaresis, John S.; Irwin, Juan C.; Goldfien, Gabriel A.; Giudice, Linda C.] Univ Calif San Francisco, Dept Obstet Gynecol & Reprod Sci, Ctr Reprod Sci, San Francisco, CA 94143 USA. [Rabban, Joseph T.] Univ Calif San Francisco, Dept Pathol, San Francisco, CA 94143 USA. [Burney, Richard O.] Madigan Healthcare Syst, Dept Obstet & Gynecol & Clin Invest, Tacoma, WA 98431 USA. [Nezhat, Camran] Stanford Univ, Dept Obstet & Gynecol, Stanford, CA 94024 USA. [DePaolo, Louis V.] NIH, Fertil & Infertil Branch, Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Bethesda, MD 20892 USA. RP Giudice, LC (reprint author), Univ Calif San Francisco, Dept Obstet Gynecol & Reprod Sci, 505 Parnassus Ave,Room 1496, San Francisco, CA 94143 USA. EM giudice@obgyn.ucsf.edu FU National Institutes of Health; Eunice Kennedy Shriver National Institute of Child Health and Human Development Specialized Cooperative Centers Program in Reproduction and Infertility Research Grant [U54HD 055764]; National Institutes of Health/University of California; San Francisco Human Endometrial Tissue and DNA Bank; University of California, San Francisco Clinical and Translational Research Institute Resource Allocation Program; University of California Office of the President Proof of Concept grant FX This work was supported by the National Institutes of Health, Eunice Kennedy Shriver National Institute of Child Health and Human Development Specialized Cooperative Centers Program in Reproduction and Infertility Research Grant U54HD 055764 (to L.C.G.), the National Institutes of Health/University of California, San Francisco Human Endometrial Tissue and DNA Bank, the University of California, San Francisco Clinical and Translational Research Institute Resource Allocation Program (L.C.G.), and a University of California Office of the President Proof of Concept grant (L.C.G.). NR 57 TC 17 Z9 17 U1 1 U2 6 PU ENDOCRINE SOC PI WASHINGTON PA 2055 L ST NW, SUITE 600, WASHINGTON, DC 20036 USA SN 0013-7227 EI 1945-7170 J9 ENDOCRINOLOGY JI Endocrinology PD DEC PY 2014 VL 155 IS 12 BP 4986 EP 4999 DI 10.1210/en.2014-1490 PG 14 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA AX0UN UT WOS:000346668000036 PM 25243856 ER PT J AU Sun, GH Fu, LZ Wen, L Shi, YB AF Sun, Guihong Fu, Liezhen Wen, Luan Shi, Yun-Bo TI Activation of Sox3 Gene by Thyroid Hormone in the Developing Adult Intestinal Stem Cell During Xenopus Metamorphosis SO ENDOCRINOLOGY LA English DT Article ID AMPHIBIAN METAMORPHOSIS; SONIC HEDGEHOG; POSTEMBRYONIC DEVELOPMENT; EPITHELIAL DEVELOPMENT; CONNECTIVE-TISSUE; LAEVIS INTESTINE; BETA-CATENIN; TR-ALPHA; RECEPTOR; DIFFERENTIATION AB The maturation of the intestine into the adult form involves the formation of adult stem cells in a thyroid hormone (T-3)-dependent process in vertebrates. In mammals, this takes place during postembryonic development, a period around birth when the T-3 level peaks. Due to the difficulty of manipulating late-stage, uterus-enclosed embryos, very little is known about the development of the adult intestinal stem cells. Interestingly, the remodeling of the intestine during the T-3-dependent amphibian metamorphosis mimics the maturation of mammalian intestine. Our earlier microarray studies in Xenopus laevis revealed that the transcription factor SRY (sex-determining region Y)-box 3 (Sox3), well known for its involvement in neural development, was upregulated in the intestinal epithelium during metamorphosis. Here, we show that Sox3 is highly and specifically expressed in the developing adult intestinal progenitor/stem cells. We further show that its induction by T-3 is independent of new protein synthesis, suggesting that Sox3 is directly activated by liganded T-3 receptor. Thus, T-3 activates Sox3 as one of the earliest changes in the epithelium, and Sox3 in turn may facilitate the dedifferentiation of the larval epithelial cells into adult stem cells. C1 [Sun, Guihong] Wuhan Univ, Sch Basic Med Sci, Wuhan 430072, Peoples R China. [Fu, Liezhen; Wen, Luan; Shi, Yun-Bo] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Sect Mol Morphogenesis, Program Cellular Regulat & Metab, NIH, Bethesda, MD 20892 USA. RP Shi, YB (reprint author), Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, NIH, Lab Gene Regulat & Dev, Bldg 18T Room 106,18 Lib Dr,MSC 5431, Bethesda, MD 20892 USA. EM shi@helix.nih.gov FU intramural Research Program of the Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health; National Natural Science Foundation of China [31370187, 30870113] FX This work 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 National Natural Science Foundation of China (Grants 31370187 and 30870113). NR 75 TC 3 Z9 3 U1 0 U2 5 PU ENDOCRINE SOC PI WASHINGTON PA 2055 L ST NW, SUITE 600, WASHINGTON, DC 20036 USA SN 0013-7227 EI 1945-7170 J9 ENDOCRINOLOGY JI Endocrinology PD DEC PY 2014 VL 155 IS 12 BP 5024 EP 5032 DI 10.1210/en.2014-1316 PG 9 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA AX0UN UT WOS:000346668000039 PM 25211587 ER PT J AU Feng, Y Zhao, Q Chen, WZ Wang, YP Crowder, K Dimitrov, DS AF Feng, Yang Zhao, Qi Chen, Weizao Wang, Yanping Crowder, Karalyne Dimitrov, Dimiter S. TI A new bispecific antibody targeting non-overlapping epitopes on IGF2: Design, in vitro characterization and pharmacokinetics in macaques SO EXPERIMENTAL AND MOLECULAR PATHOLOGY LA English DT Article DE IGF ligand; Bispecific antibodies; Half-life; Cynomolgus macaques ID HUMAN MONOCLONAL-ANTIBODIES; GROWTH-FACTOR-II; PHASE-2 TRIAL; INSULIN; CANCER; RECEPTOR; TUMORS; INHIBITION; BINDING AB The insulin-like growth factor 2 (IGF2) is an important target for cancer therapy. We have previously proposed an approach for fast and irreversible removal of IGF2 from the circulation by using monoclonal antibodies (mAbs) that bind to two or more non-overlapping epitopes on the same molecule. We provided initial evidence for the formation of oligomeric antibody-ligand complexes that can bind to cells expressing Fc gamma receptors (Fc gamma Rs) with high avidity using an antibody domain with relatively low affinity as one of the anti-IGF2 mAbs. Recently, we identified a mAb, m708.5, in a scFv format which binds to both IGF2 and IGF1 with very high (pM) affinity. Interestingly, and rather surprisingly, this mAb did not compete with our other high affinity mAb, m610.27, for binding to IGF2. Therefore, we generated a new bispecific mAb, m67, by combining m708.5 and m610.27. As expected m67 potently inhibited binding of IGF2 to cells expressing the IGF1R and its phosphorylation, and resulted in formation of multimolecular complexes when incubated with IGF2 and bound with high avidity to cells expressing Fc gamma RII; the complexes were internalized in a macrophage-like cell line. However, although m67 exhibited a reasonably long half-life (6.4 +/- 0.6 days) in cynomolgus macaques and high stability in serum, its administration to three animals did not result in any measurable decrease in the IGF2 concentration likely due to the complexity of the IGF2 interactions in the blood and the relatively low (2 mg/kg) dose of the mAb leading to a relatively low maximal blood concentration of 120 nM. In spite of the lack of effect on the IGF2 concentration in this particular experimental setup, m67 exhibited good drugability properties and could be highly effective in other animal models and in humans. Studies with animal models of cancer are ongoing to evaluate the potential of m67 as a new candidate mAb-based therapeutic. Published by Elsevier Inc. C1 [Feng, Yang; Chen, Weizao; Wang, Yanping; Dimitrov, Dimiter S.] NCI, Ctr Canc Res, Prot Interact Grp, Canc & Inflammat Program, Frederick, MD 21702 USA. [Zhao, Qi] Chinese Acad Sci, Shenzhen Inst Adv Technol, Guangzhou 518000, Guangdong, Peoples R China. [Wang, Yanping] Geneva Fdn, Tacoma, WA 98402 USA. [Crowder, Karalyne] SNBL USA, Everett, WA 98203 USA. RP Feng, Y (reprint author), NCI, Bldg 567,Rm180,1050 Boyles St, Frederick, MD 21702 USA. EM fengya@mail.nih.gov FU Intramural Research Program of the Center for Cancer Research, National Cancer Institute, National Institutes of Health [NO1-CO-12400, HHSN261200800001E] FX This work was supported by the Intramural Research Program of the Center for Cancer Research, National Cancer Institute, National Institutes of Health (Contract No. NO1-CO-12400 and HHSN261200800001E). NR 22 TC 4 Z9 4 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 0014-4800 EI 1096-0945 J9 EXP MOL PATHOL JI Exp. Mol. Pathol. PD DEC PY 2014 VL 97 IS 3 BP 359 EP 367 DI 10.1016/j.yexmp.2014.09.007 PG 9 WC Pathology SC Pathology GA AX1CK UT WOS:000346685700007 PM 25220345 ER PT J AU Neuman, MG French, SW French, BA Seitz, HK Cohen, LB Mueller, S Osna, NA Kharbanda, KK Seth, D Bautista, A Thompson, KJ McKillop, IH Kirpich, IA McClain, CJ Bataller, R Nanau, RM Voiculescu, M Opris, M Shen, H Tillman, B Li, J Liu, H Thomes, PG Ganesan, M Malnick, S AF Neuman, Manuela G. French, Samuel W. French, Barbara A. Seitz, Helmut K. Cohen, Lawrence B. Mueller, Sebastian Osna, Natalia A. Kharbanda, Kusum K. Seth, Devanshi Bautista, Abraham Thompson, Kyle J. McKillop, Iain H. Kirpich, Irina A. McClain, Craig J. Bataller, Ramon Nanau, Radu M. Voiculescu, Mihai Opris, Mihai Shen, Hong Tillman, Brittany Li, Jun Liu, Hui Thomes, Paul G. Ganesan, Murali Malnick, Steve TI Alcoholic and non-alcoholic steatohepatitis SO EXPERIMENTAL AND MOLECULAR PATHOLOGY LA English DT Review DE Alcoholic hepatitis; Nonalcoholic steatohepatitis; Alcoholic liver disease; CYP2E1; Hangover; Hepatocarcinogenesis; Immunohistochemistry; Laboratory markers; Mallory-Denk bodies; Methylation; Mitochondrion; Micronutrients; Viral hepatitis; Human immunodeficiency virus ID FATTY LIVER-DISEASE; CARBOHYDRATE-DEFICIENT TRANSFERRIN; HEPATITIS-C VIRUS; HEPATOCYTE NUCLEAR FACTOR-4-ALPHA; HUMAN HEPATOCELLULAR-CARCINOMA; GAMMA-GLUTAMYL-TRANSFERASE; CHRONIC ETHANOL INGESTION; INDUCED OXIDATIVE STRESS; MALLORY-DENK BODIES; METABOLIC SYNDROME AB This paper is based upon the "Charles Lieber Satellite Symposia" organized by Manuela G. Neuman at the Research Society on Alcoholism (RSA) Annual Meetings, 2013 and 2014. The present review includes pre-clinical, translational and clinical research that characterize alcoholic liver disease (ALD) and non-alcoholic steatohepatitis (NASH). In addition, a literature search in the discussed area was performed. Strong clinical and experimental evidence lead to recognition of the key toxic role of alcohol in the pathogenesis of ALD. The liver biopsy can confirm the etiology of NASH or alcoholic steatohepatitis (ASH) and assess structural alterations of cells, their organelles, as well as inflammatory activity. Three histological stages of ALD are simple steatosis, ASH, and chronic hepatitis with hepatic fibrosis or cirrhosis. These latter stages may also be associated with a number of cellular and histological changes, including the presence of Mallory's hyaline, megamitochondria, or perivenular and perisinusoidal fibrosis. Genetic polymorphisms of ethanol metabolizing enzymes such as cytochrome p450 (CYP) 2E1 activation may change the severity of ASH and NASH. Alcohol mediated hepatocarcinogenesis, immune response to alcohol in ASH, as well as the role of other risk factors such as its co-morbidities with chronic viral hepatitis in the presence or absence of human immunodeficiency virus are discussed. Dysregulation of hepatic methylation, as result of ethanol exposure, in hepatocytes transfected with hepatitis C virus (HCV), illustrates an impaired interferon signaling. The hepatotoxic effects of ethanol undermine the contribution of malnutrition to the liver injury. Dietary interventions such as micro and macronutrients, as well as changes to the microbiota are suggested. The clinical aspects of NASH, as part of metabolic syndrome in the aging population, are offered. The integrative symposia investigate different aspects of alcohol-induced liver damage and possible repair. We aim to (1) determine the immuno-pathology of alcohol-induced liver damage, (2) examine the role of genetics in the development of ASH, (3) propose diagnostic markers of ASH and NASH, (4) examine age differences, (5) develop common research tools to study alcohol-induced effects in clinical and pre-clinical studies, and (6) focus on factors that aggravate severity of organ-damage. The intention of these symposia is to advance the international profile of the biological research on alcoholism. We also wish to further our mission of leading the forum to progress the science and practice of translational research in alcoholism. (C) 2014 Elsevier Inc. All rights reserved. C1 [Neuman, Manuela G.; Nanau, Radu M.; Opris, Mihai] Univ Toronto, Toronto, ON M5G 0A3, Canada. [Neuman, Manuela G.] Univ Toronto, Fac Med, Dept Pharmacol & Toxicol, Toronto, ON M5G 0A3, Canada. [French, Samuel W.; French, Barbara A.; Shen, Hong; Tillman, Brittany; Li, Jun; Liu, Hui] Harbor UCLA Med Ctr, Torrance, CA 90509 USA. [Seitz, Helmut K.; Mueller, Sebastian] Heidelberg Univ, Alcohol Res Ctr, Heidelberg, Germany. [Seitz, Helmut K.; Mueller, Sebastian] Salem Med Ctr, Dept Med Gastroenterol & Hepatol, Heidelberg, Germany. [Cohen, Lawrence B.] Univ Toronto, Fac Med, Sunnybrook Hlth Sci Ctr, Dept Med,Div Gastroenterol, Toronto, ON M5G 0A3, Canada. [Osna, Natalia A.; Kharbanda, Kusum K.; Thomes, Paul G.; Ganesan, Murali] Univ Nebraska, Med Ctr, Vet Affairs Nebraska Western Iowa Hlth Care Syst, Res Serv, Omaha, NE 68182 USA. [Seth, Devanshi] Royal Prince Alfred Hosp, Centenary Inst Canc Med & Cell Biol, Drug Hlth Serv, Camperdown, NSW 2050, Australia. [Seth, Devanshi] Univ Sydney, Fac Med, Sydney, NSW 2006, Australia. [Bautista, Abraham] NIAAA, Off Extramural Activ, NIH, Rockville, MD 20852 USA. [Thompson, Kyle J.; McKillop, Iain H.] NIAAA, Off Extramural Activ, NIH, Rockville, MD 20852 USA. [McClain, Craig J.] Univ Louisville, Sch Med, Louisville, KY 40292 USA. [Bataller, Ramon] Robley Rex Vet Med Ctr, Louisville, KY USA. [Bataller, Ramon] Univ N Carolina, Dept Med, Div Gastroenterol & Hepatol, Chapel Hill, NC USA. [Malnick, Steve] Univ N Carolina, Dept Nutr, Chapel Hill, NC USA. [Malnick, Steve] Kaplan Med Ctr, Dept Internal Med, Rehovot, Israel. [Voiculescu, Mihai] Hebrew Univ Jerusalem, IL-76100 Rehovot, Israel. [Opris, Mihai] Fundeni Clin Inst, Div Nephrol & Internal Med, Bucharest, Romania. [Opris, Mihai] Univ Med & Pharm Carol Davila, Bucharest, Romania. [Opris, Mihai] Family Med Clin CAR, Bucharest, Romania. RP Neuman, MG (reprint author), Univ Toronto, Fac Med, Vitro Drug Safety & Biotechnol Banting Inst, Dept Pharmacol & Toxicol, 100 Coll St,Lab 217, Toronto, ON M5G 0A3, Canada. EM manuela.neuman@utoronto.ca FU NIH [AAUOI-021848-02, P50-11999]; Merit Review grants from the Department of Veterans Affairs, Office of Research and Development (Biomedical Laboratory and Development) [BX001673, BX001155]; In Vitro Drug Safety and Biotechnology; Mahaffy Grant, Sunnybrook HSC FX S. French and his team thank Adriana Flores for typing the manuscript and thank NIH for the grant support (AAUOI-021848-02 and P50-11999 Morphology Core).; Drs. Osna and Kharbanda acknowledge that their research reported here was supported by Merit Review grants BX001673 (NAO) and BX001155 (KKK) from the Department of Veterans Affairs, Office of Research and Development (Biomedical Laboratory and Development).; Drs. Neuman and Cohen thank In Vitro Drug Safety and Biotechnology and Mahaffy Grant, Sunnybrook HSC for the funding. NR 243 TC 16 Z9 16 U1 9 U2 40 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0014-4800 EI 1096-0945 J9 EXP MOL PATHOL JI Exp. Mol. Pathol. PD DEC PY 2014 VL 97 IS 3 BP 492 EP 510 DI 10.1016/j.yexmp.2014.09.005 PG 19 WC Pathology SC Pathology GA AX1CK UT WOS:000346685700024 PM 25217800 ER PT J AU Kang, E Gennery, A AF Kang, Elizabeth Gennery, Andrew TI Hematopoietic Stem Cell Transplantation for Primary Immunodeficiencies SO HEMATOLOGY-ONCOLOGY CLINICS OF NORTH AMERICA LA English DT Article DE Immunodeficiency; Immune reconstitution; Infection; Immunosuppression; Inflammation ID BONE-MARROW-TRANSPLANTATION; CHRONIC GRANULOMATOUS-DISEASE; WISKOTT-ALDRICH-SYNDROME; TERM IMMUNE RECONSTITUTION; IN-UTERO TRANSPLANTATION; CERNUNNOS-XLF DEFICIENCY; SINGLE-CENTER EXPERIENCE; HYPER-IGE SYNDROME; DNA-LIGASE-IV; DOCK8 DEFICIENCY AB Allogeneic hematopoietic stem cell transplantation has been shown to be curative for well-described as well as newly discovered immunodeficiencies. However, it is difficult to define a universal transplant regimen given the rarity of these disorders and the varied pathophysiology these disorders encompass. This article discusses those primary immunodeficiencies most commonly treated by hematopoietic stem cell transplant and describes the transplant issues specific to these disorders. C1 [Kang, Elizabeth] NIAID, Hematotherapeut Unit, Lab Host Def, NIH, Bethesda, MD 20892 USA. [Gennery, Andrew] Great North Childrens Hosp, Inst Cellular Med, Paediat Immunol Dept, Newcastle Upon Tyne NE1 4LP, Tyne & Wear, England. RP Kang, E (reprint author), NIAID, Hematotherapeut Unit, Lab Host Def, NIH, 10-CRC Room 6-3752,10 Ctr Dr, Bethesda, MD 20892 USA. EM ekang@niaid.nih.gov FU Intramural NIH HHS [Z99 AI999999] NR 97 TC 1 Z9 2 U1 1 U2 11 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0889-8588 EI 1558-1977 J9 HEMATOL ONCOL CLIN N JI Hematol. Oncol. Clin. North Am. PD DEC PY 2014 VL 28 IS 6 BP 1157 EP + DI 10.1016/j.hoc.2014.08.006 PG 15 WC Oncology; Hematology SC Oncology; Hematology GA AX1CS UT WOS:000346686500013 PM 25459185 ER PT J AU Bras, J Guerreiro, R Darwent, L Parkkinen, L Ansorge, O Escott-Price, V Hernandez, DG Nalls, MA Clark, LN Honig, LS Marder, K Van Der Flier, WM Lemstra, A Scheltens, P Rogaeva, E St George-Hyslop, P Londos, E Zetterberg, H Ortega-Cubero, S Pastor, P Ferman, TJ Graff-Radford, NR Ross, OA Barber, I Braae, A Brown, K Morgan, K Maetzler, W Berg, D Troakes, C Al-Sarraj, S Lashley, T Compta, Y Revesz, T Lees, A Cairns, N Halliday, GM Mann, D Pickering-Brown, S Dickson, DW Singleton, A Hardy, J AF Bras, Jose Guerreiro, Rita Darwent, Lee Parkkinen, Laura Ansorge, Olaf Escott-Price, Valentina Hernandez, Dena G. Nalls, Michael A. Clark, Lorraine N. Honig, Lawrence S. Marder, Karen Van Der Flier, Wiesje M. Lemstra, Afina Scheltens, Philip Rogaeva, Ekaterina St George-Hyslop, Peter Londos, Elisabet Zetterberg, Henrik Ortega-Cubero, Sara Pastor, Pau Ferman, Tanis J. Graff-Radford, Neill R. Ross, Owen A. Barber, Imelda Braae, Anne Brown, Kristelle Morgan, Kevin Maetzler, Walter Berg, Daniela Troakes, Claire Al-Sarraj, Safa Lashley, Tammaryn Compta, Yaroslau Revesz, Tamas Lees, Andrew Cairns, Nigel Halliday, Glenda M. Mann, David Pickering-Brown, Stuart Dickson, Dennis W. Singleton, Andrew Hardy, John TI Genetic analysis implicates APOE, SNCA and suggests lysosomal dysfunction in the etiology of dementia with Lewy bodies SO HUMAN MOLECULAR GENETICS LA English DT Article ID GENOME-WIDE ASSOCIATION; ALZHEIMERS-DISEASE; PARKINSONS-DISEASE; GLUCOCEREBROSIDASE MUTATIONS; IDENTIFIES VARIANTS; DIAGNOSIS; MULTICENTER; PATHOLOGY; RISK; DLB AB Clinical and neuropathological similarities between dementia with Lewy bodies (DLB), Parkinson's and Alzheimer's diseases (PD and AD, respectively) suggest that these disorders may share etiology. To test this hypothesis, we have performed an association study of 54 genomic regions, previously implicated in PD or AD, in a large cohort of DLB cases and controls. The cohort comprised 788 DLB cases and 2624 controls. To minimize the issue of potential misdiagnosis, we have also performed the analysis including only neuropathologically proven DLB cases (667 cases). The results show that the APOE is a strong genetic risk factor for DLB, confirming previous findings, and that the SNCA and SCARB2 loci are also associated after a study-wise Bonferroni correction, although these have a different association profile than the associations reported for the same loci in PD. We have previously shown that the p.N370S variant in GBA is associated with DLB, which, together with the findings at the SCARB2 locus, suggests a role for lysosomal dysfunction in this disease. These results indicate that DLB has a unique genetic risk profile when compared with the two most common neurodegenerative diseases and that the lysosome may play an important role in the etiology of this disorder. We make all these data available. C1 [Bras, Jose; Guerreiro, Rita; Darwent, Lee] UCL Inst Neurol, Dept Mol Neurosci, London WC1N 3BG, England. [Lashley, Tammaryn; Compta, Yaroslau; Revesz, Tamas; Lees, Andrew] UCL Inst Neurol, Queen Sq Brain Bank, Dept Mol Neurosci, London WC1N 3BG, England. [Hardy, John] UCL Inst Neurol, Reta Lila Weston Res Labs, Dept Mol Neurosci, London WC1N 3BG, England. [Parkkinen, Laura; Ansorge, Olaf] Univ Oxford, Nuffield Dept Clin Neurosci, Oxford Parkinsons Dis Ctr, Oxford, England. [Escott-Price, Valentina] Cardiff Univ, Sch Med, MRC Ctr Neuropsychiatr Genet & Genom, Cardiff CF10 3AX, S Glam, Wales. [Hernandez, Dena G.; Nalls, Michael A.; Singleton, Andrew] NIA, Neurogenet Lab, NIH, Bethesda, MD 20892 USA. [Clark, Lorraine N.; Honig, Lawrence S.; Marder, Karen] Columbia Univ, Taub Inst Alzheimer Dis & Aging Brain, New York, NY USA. [Clark, Lorraine N.] Columbia Univ, Dept Pathol & Cell Biol, New York, NY USA. [Honig, Lawrence S.; Marder, Karen] Columbia Univ, Dept Neurol, New York, NY USA. [Van Der Flier, Wiesje M.; Lemstra, Afina; Scheltens, Philip] Vrije Univ Amsterdam, Med Ctr, Dept Neurol, Amsterdam, Netherlands. [Van Der Flier, Wiesje M.; Lemstra, Afina; Scheltens, Philip] Vrije Univ Amsterdam, Med Ctr, Alzheimer Ctr, Amsterdam, Netherlands. [Rogaeva, Ekaterina; St George-Hyslop, Peter] Univ Toronto, Dept Med, Tanz Ctr Res Neurodegenerat Dis, Toronto, ON, Canada. [St George-Hyslop, Peter] Univ Cambridge, Cambridge Inst Med Res, Cambridge CB2 0XY, England. [St George-Hyslop, Peter] Univ Cambridge, Cambridge Natl Inst Hlth Res Biomed Res Unit Deme, Cambridge CB2 0XY, England. [Londos, Elisabet] Lund Univ, Clin Memory Res Unit, Inst Clin Sci Malmo, S-22100 Lund, Sweden. [Zetterberg, Henrik] Univ Gothenburg, Clin Neurochem Lab, Dept Psychiat & Neurochem, Inst Neurosci & Physiol,Sahlgrenska Acad, Molndal, Sweden. [Ortega-Cubero, Sara; Pastor, Pau] Univ Navarra, Neurogenet Lab, Div Neurosci, Ctr Appl Med Res, E-31080 Pamplona, Spain. [Ortega-Cubero, Sara; Pastor, Pau] Univ Navarra, Sch Med, Dept Neurol, Univ Navarra Clin, E-31080 Pamplona, Spain. [Ortega-Cubero, Sara; Pastor, Pau] Inst Salud Carlos III, CIBERNED, Ctr Invest Biomed Red Enfermedades Neurodegenerat, Madrid, Spain. [Ferman, Tanis J.] Mayo Clin, Dept Psychiat, Jacksonville, FL 32224 USA. [Ferman, Tanis J.] Mayo Clin, Dept Psychol, Jacksonville, FL 32224 USA. [Graff-Radford, Neill R.] Mayo Clin, Dept Neurol, Jacksonville, FL 32224 USA. [Ross, Owen A.; Dickson, Dennis W.] Mayo Clin, Dept Neurosci, Jacksonville, FL 32224 USA. [Barber, Imelda; Braae, Anne; Brown, Kristelle; Morgan, Kevin] Univ Nottingham, Sch Life Sci, Queens Med Ctr, Nottingham NG7 2RD, England. [Maetzler, Walter; Berg, Daniela] Univ Tubingen, Hertie Inst Clin Brain Res, Dept Neurodegenerat, Ctr Neurol, Tubingen, Germany. [Maetzler, Walter; Berg, Daniela] German Ctr Neurodegenerat Dis, DZNE, Tubingen, Germany. [Troakes, Claire; Al-Sarraj, Safa] Kings Coll London, Inst Psychiat, MRC London Neurodegenerat Dis Brain Bank, Dept Clin Neurosci, London WC2R 2LS, England. [Cairns, Nigel] Washington Univ, Sch Med, Knight Alzheimers Dis Res Ctr, St Louis, MO USA. [Cairns, Nigel] Washington Univ, Sch Med, Dept Neurol, St Louis, MO 63110 USA. [Halliday, Glenda M.] Neurosci Res Australia, Sydney, NSW, Australia. [Halliday, Glenda M.] Univ New S Wales, Sch Med Sci, Fac Med, Sydney, NSW, Australia. [Mann, David; Pickering-Brown, Stuart] Univ Manchester, Fac Med & Human Sci, Inst Brain Behav & Mental Hlth, Manchester, Lancs, England. [Compta, Yaroslau] Hosp Clin Barcelona, Parkinsons Dis & Movement Disorders Unit, Neurol Serv, IDIBAPS,CIBERNED, Barcelona, Catalonia, Spain. RP Bras, J (reprint author), UCL Inst Neurol, Dept Mol Neurosci, Queen Sq House,Queen Sq, London WC1N 3BG, England. EM j.bras@ucl.ac.uk RI Pastor, Pau/C-9834-2009; Lashley, Tammaryn/D-2583-2009; Hardy, John/C-2451-2009; Singleton, Andrew/C-3010-2009; Halliday, Glenda/E-8555-2011; Pickering-Brown, Stuart/D-4008-2009; Troakes, Claire/K-4346-2015; Maetzler, Walter/A-6796-2011; Guerreiro, Rita/A-1327-2011; Revesz, Tamas/A-8732-2010; OI Pastor, Pau/0000-0002-7493-8777; Bras, Jose/0000-0001-8186-0333; Halliday, Glenda/0000-0003-0422-8398; Pickering-Brown, Stuart/0000-0003-1561-6054; Revesz, Tamas/0000-0003-2501-0259; Escott-Price, Valentina/0000-0003-1784-5483 FU Parkinson's UK [K-1204]; Wellcome Trust/MRC [WT089698]; Alzheimer's Research UK; Spanish Ministry of Science and Innovation [SAF2006-10126, SAF2010-22329-C02-01]; UTE project FIMA; Stichting Dioraphte; Stichting VUMC fonds; Wellcome Trust; Medical Research Council; Canadian Institutes of Health Research; Ontario Research Fund; ARUK; Big Lottery Fund; Taub Institute; Panasci Fund; Parkinson's Disease Foundation; NIH [NS060113, P50AG008702, P50NS038370, UL1TR000040]; Michael J. Fox Foundation; NINDS [NS078086]; Mangurian Foundation for Lewy body research; Queen Square Brain Bank at the UCL Institute of Neurology; Alzheimer's Society; NIHR UCLH Biomedical Research Centre; Queen Square Dementia Biomedical Research Unit; National Institute on Aging, National Institutes of Health, Department of Health and Human Services [AG000951-12] FX This work was supported in part by a Parkinson's UK Innovation Award (K-1204) and by the Wellcome Trust/MRC Joint Call in Neurodegeneration award (WT089698) to the UK Parkinson's Disease Consortium whose members are from the UCL Institute of Neurology, the University of Sheffield, and the MRC Protein Phosphorylation Unit at the University of Dundee and by an anonymous Foundation. R.G. is supported by an Alzheimer's Research UK Travelling Fellowship. The authors would like to acknowledge Elena Lorenzo for her technical assistance. This study was supported in part by grants from the Spanish Ministry of Science and Innovation SAF2006-10126 (2006-2009) and SAF2010-22329-C02-01 (2011-2013) to P.P. and by the UTE project FIMA to P.P. The sample collection and database of the Amsterdam Dementia Cohort was funded by Stichting Dioraphte and Stichting VUMC fonds. G.M.H. is a Senior Principal Research Fellow of the National Health and Medical Research Council of Australia. For the neuropathologically confirmed samples from Australia, brain tissue was received from the Sydney Brain Bank, which is supported by Neuroscience Research Australia, the University of New South Wales and the National Health and Medical Research Council of Australia. This study was also partially funded by the Wellcome Trust, Medical Research Council, Canadian Institutes of Health Research, Ontario Research Fund. The Nottingham Genetics Group is supported by ARUK and The Big Lottery Fund. The effort from Columbia University was supported by the Taub Institute, the Panasci Fund, the Parkinson's Disease Foundation, and NIH grants NS060113 (L. Clark), P50AG008702 (P.I. Scott Small), P50NS038370 (P.I. R. Burke), and UL1TR000040 (P.I. H. Ginsberg). O.A.R. is supported by the Michael J. Fox Foundation, NINDS R01# NS078086. The Mayo Clinic Jacksonville is a Morris K. Udall Parkinson's Disease Research Center of Excellence (NINDS P50 #NS072187) and is supported by the Mangurian Foundation for Lewy body research. This work has received support from The Queen Square Brain Bank at the UCL Institute of Neurology. Some of the tissue samples studied were provided by the MRC London Neurodegenerative Diseases Brain Bank and the Brains for Dementia Research project (funded by Alzheimer's Society and ARUK). This research was supported in part by both the NIHR UCLH Biomedical Research Centre and the Queen Square Dementia Biomedical Research Unit. This work was supported in part by the Intramural Research Program of the National Institute on Aging, National Institutes of Health, Department of Health and Human Services; project AG000951-12. Funding to pay the Open Access publication charges for this article was provided by the Wellcome Trust and the Medical Research Council. NR 31 TC 39 Z9 39 U1 2 U2 11 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0964-6906 EI 1460-2083 J9 HUM MOL GENET JI Hum. Mol. Genet. PD DEC 1 PY 2014 VL 23 IS 23 BP 6139 EP 6146 DI 10.1093/hmg/ddu334 PG 8 WC Biochemistry & Molecular Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Genetics & Heredity GA AX2MF UT WOS:000346777400001 PM 24973356 ER PT J AU Squires, RB Pickett, BE Das, S Scheuermann, RH AF Squires, R. Burke Pickett, Brett E. Das, Sajal Scheuermann, Richard H. TI Toward a method for tracking virus evolutionary trajectory applied to the pandemic H1N1 2009 influenza virus SO INFECTION GENETICS AND EVOLUTION LA English DT Article DE Influenza; Virus; Evolution; Metadata; Swine flu; Pandemic ID A VIRUS; MUTATION-RATES; ORIGIN; GENES; PERFORMANCE AB In 2009 a novel pandemic H1N1 influenza virus (H1N1pdm09) emerged as the first official influenza pandemic of the 21st century. Early genomic sequence analysis pointed to the swine origin of the virus. Here we report a novel computational approach to determine the evolutionary trajectory of viral sequences that uses data-driven estimations of nucleotide substitution rates to track the gradual accumulation of observed sequence alterations over time. Phylogenetic analysis and multiple sequence alignments show that sequences belonging to the resulting evolutionary trajectory of the H1N1pdm09 lineage exhibit a gradual accumulation of sequence variations and tight temporal correlations in the topological structure of the phylogenetic trees. These results suggest that our evolutionary trajectory analysis (ETA) can more effectively pinpoint the evolutionary history of viruses, including the host and geographical location traversed by each segment, when compared against either BLAST or traditional phylogenetic analysis alone. (C) 2014 Elsevier B.V. All rights reserved. C1 [Squires, R. Burke] NIAID, Bioinformat & Computat Biosci Branch, Off Cyber Infrastruct & Computat Biol, NIH, Bethesda, MD 20892 USA. [Pickett, Brett E.; Scheuermann, Richard H.] J Craig Venter Inst, La Jolla, CA USA. [Das, Sajal] Missouri Univ Sci & Technol, Dept Comp Sci, Rolla, MO USA. [Scheuermann, Richard H.] Univ Calif San Diego, Dept Pathol, San Diego, CA 92103 USA. RP Squires, RB (reprint author), NIAID, Bioinformat & Computat Biosci Branch, Off Cyber Infrastruct & Computat Biol, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA. EM richard.squires@nih.gov OI Squires, R Burke/0000-0001-9666-6285 FU NIAID [N01AI40041] FX Thanks to Megan Coakley for critical reading of the manuscript. We also acknowledge the generous support received from the NIAID - N01AI40041. NR 16 TC 1 Z9 1 U1 5 U2 31 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 1567-1348 EI 1567-7257 J9 INFECT GENET EVOL JI Infect. Genet. Evol. PD DEC PY 2014 VL 28 BP 351 EP 357 DI 10.1016/j.meegid.2014.07.015 PG 7 WC Infectious Diseases SC Infectious Diseases GA AX1YI UT WOS:000346739500053 PM 25064525 ER PT J AU Huestis, DL Lehmann, T AF Huestis, Diana L. Lehmann, Tovi TI Ecophysiology of Anopheles gambiae s.l.: Persistence in the Sahel SO INFECTION GENETICS AND EVOLUTION LA English DT Article DE Aestivation; Diapause; Dormancy; Geographic variation; Malaria; Vector ecology ID MOSQUITO CULEX-PIPIENS; OVIPOSITION-SITE DEPRIVATION; DISCONTINUOUS GAS-EXCHANGE; METABOLIC-RATE DEPRESSION; MOTH CYMBALOPHORA-PUDICA; NORTHERN HOUSE MOSQUITO; DRY SEASON; DESICCATION RESISTANCE; CULISETA-INORNATA; SUMMER DIAPAUSE AB The dry-season biology of malaria vectors is poorly understood, especially in arid environments when no surface waters are available for several months, such as during the dry season in the Sahel. Here we reappraise results on the dry-season physiology of members of the Anopheles gambiae s.l. complex in the broad context of dormancy in insects and especially in mosquitoes. We examine evidence on seasonal changes in reproduction, metabolism, stress tolerance, nutrition, molecular regulation, and environmental conditions and determine if the current results are compatible with dry-season diapause (aestivation) as the primary strategy for persistence throughout the dry season in the Sahel. In the process, we point out critical gaps in our knowledge that future studies can fill. We find compelling evidence that members of the An. gambiae s.l. complex undergo a form of aestivation during the Sahelian dry season by shifting energetic resources away from reproduction and towards increased longevity. Considering the differences between winter at temperate latitudes, which entails immobility of the insect and hence reliance on physiological solutions, as opposed to the Sahelian dry season, which restricts reproduction exclusively, we propose that behavioral changes play an important role in complementing physiological changes in this strategy. (C) 2014 Elsevier B.V. All rights reserved. C1 [Huestis, Diana L.; Lehmann, Tovi] NIAID, Lab Malaria & Vector Res, NIH, Rockville, MD 20852 USA. RP Huestis, DL (reprint author), 12735 Twinbrook Pkwy,Room 2W-13A, Rockville, MD 20852 USA. EM diana.huestis@nih.gov FU Division of Intramural Research, NIAID, NIH FX We thank Dia Elnaiem, Peter Armbruster, Phil Lounibos, and 1 anonymous reviewer for their comments on earlier versions of this manuscript. Research conducted by the authors mentioned throughout was supported by the Division of Intramural Research, NIAID, NIH. NR 145 TC 9 Z9 9 U1 2 U2 18 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 1567-1348 EI 1567-7257 J9 INFECT GENET EVOL JI Infect. Genet. Evol. PD DEC PY 2014 VL 28 BP 648 EP 661 DI 10.1016/j.meegid.2014.05.027 PG 14 WC Infectious Diseases SC Infectious Diseases GA AX1YI UT WOS:000346739500084 PM 24933461 ER PT J AU Abdeladhim, M Kamhawi, S Valenzuela, JG AF Abdeladhim, Maha Kamhawi, Shaden Valenzuela, Jesus G. TI What's behind a sand fly bite? The profound effect of sand fly saliva on host hemostasis, inflammation and immunity SO INFECTION GENETICS AND EVOLUTION LA English DT Article DE Sand flies; Salivary protein; Immunity; Leishmaniasis; Vaccine; Transcriptomes ID LUTZOMYIA-LONGIPALPIS SALIVA; TRANSMITTED LEISHMANIA-MAJOR; POSSIBLE ETIOLOGIC LINK; VISCERAL LEISHMANIASIS; PHLEBOTOMUS-PAPATASI; CUTANEOUS LEISHMANIASIS; ANTI-DESMOGLEIN-1 ANTIBODIES; BRAZILIENSIS INFECTION; VASODILATORY PEPTIDE; GLAND TRANSCRIPTOMES AB Sand flies are blood-feeding insects and vectors of the Leishmania parasite. For many years, saliva of these insects has represented a gold mine for the discovery of molecules with anti- hemostatic and immunomodulatory activities. Furthermore, proteins in sand fly saliva have been shown to be a potential vaccine against leishmaniasis and also markers of vector exposure. A bottleneck to progress in these areas of research has been the identification of molecules responsible for the observed activities and properties of saliva. Over the past decade, rapid advances in transcriptomics and proteomics resulted in the completion of a number of sialomes (salivary gland transcriptomes) and the expression of several recombinant salivary proteins from different species of sand fly vectors. This review will provide readers with a comprehensive update of recent advances in the characterization of these salivary molecules and their biological activities and offer insights pertaining to their protective effect against leishmaniasis and their potential as markers of vector exposure. Published by Elsevier B.V. This is an open access article under the CC BY-NC-ND license C1 [Abdeladhim, Maha; Kamhawi, Shaden; Valenzuela, Jesus G.] NIAID, Vector Mol Biol Sect, Lab Malaria & Vector Res, NIH, Rockville, MD 20852 USA. RP Kamhawi, S (reprint author), NIAID, Vector Mol Biol Sect, Lab Malaria & Vector Res, NIH, Rockville, MD 20852 USA. EM skamhawi@niaid.nih.gov; jvalenzuela@niaid.nih.gov FU Intramural Research Program of the NIH; National Institute of Allergy and Infectious Diseases, United States FX M.A., S.K. and J.G.V. were supported by the Intramural Research Program of the NIH, National Institute of Allergy and Infectious Diseases, United States. NR 90 TC 14 Z9 14 U1 0 U2 13 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 1567-1348 EI 1567-7257 J9 INFECT GENET EVOL JI Infect. Genet. Evol. PD DEC PY 2014 VL 28 BP 691 EP 703 DI 10.1016/j.meegid.2014.07.028 PG 13 WC Infectious Diseases SC Infectious Diseases GA AX1YI UT WOS:000346739500089 PM 25117872 ER PT J AU Saag, MS Masur, H AF Saag, Michael S. Masur, Henry TI HIV/AIDS Preface SO INFECTIOUS DISEASE CLINICS OF NORTH AMERICA LA English DT Editorial Material C1 [Saag, Michael S.] Univ Alabama Birmingham, Ctr AIDS Res, Birmingham, AL 35294 USA. [Masur, Henry] NIH, Dept Crit Care Med, Bethesda, MD 20892 USA. RP Saag, MS (reprint author), Univ Alabama Birmingham, Ctr AIDS Res, 845 19th St South BBRB 256, Birmingham, AL 35294 USA. EM msaag@uab.edu; hmasur@cc.nih.gov NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0891-5520 EI 1557-9824 J9 INFECT DIS CLIN N AM JI Infect. Dis. Clin. North Am. PD DEC PY 2014 VL 28 IS 4 BP IX EP X DI 10.1016/j.idc.2014.09.001 PG 2 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA AX1BC UT WOS:000346682400001 PM 25455316 ER PT J AU Beekmann, SE Henderson, DK AF Beekmann, Susan E. Henderson, David K. TI Prevention of Human Immunodeficiency Virus and AIDS Postexposure Prophylaxis (Including Health Care Workers) SO INFECTIOUS DISEASE CLINICS OF NORTH AMERICA LA English DT Article DE HIV; Postexposure prophylaxis; Occupational exposure; Nonoccupational exposure; HIV PEP ID TRANSMITTED DRUG-RESISTANCE; OCCUPATIONAL-EXPOSURE; NEEDLESTICK INJURY; HIV SEROCONVERSION; SEXUAL EXPOSURE; UNITED-STATES; TRANSMISSION; INFECTION; NEVIRAPINE; MACAQUES AB Postexposure prophylaxis (PEP), which is designed to prevent human immunodeficiency virus (HIV) infection after an exposure, is one of several strategies for HIV prevention. PEP was first used after occupational HIV exposures in the late 1980s, with the Centers for Disease Control and Prevention issuing the first set of guidelines that included considerations regarding the use of antiretroviral agents for PEP after occupational HIV exposures in 1990. Use of PEP has been extended to nonoccupational exposures, including after sexual contact or injection-drug use. This article provides a rationale for PEP, assessment of the need for PEP, and details of its implementation. C1 [Beekmann, Susan E.] Univ Iowa, Coll Med, Dept Internal Med, Iowa City, IA 52242 USA. [Henderson, David K.] NIH, Ctr Clin, Bethesda, MD 20892 USA. RP Henderson, DK (reprint author), NIH, Ctr Clin, Bldg 10 CRC,Rm 6-2551, Bethesda, MD 20892 USA. EM DHenderson@cc.nih.gov FU Intramural NIH HHS [Z99 CL999999] NR 55 TC 2 Z9 2 U1 0 U2 5 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0891-5520 EI 1557-9824 J9 INFECT DIS CLIN N AM JI Infect. Dis. Clin. North Am. PD DEC PY 2014 VL 28 IS 4 BP 601 EP + DI 10.1016/j.idc.2014.08.005 PG 14 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA AX1BC UT WOS:000346682400006 PM 25287589 ER PT J AU Fojo, T Mailankody, S Lo, A AF Fojo, Tito Mailankody, Sham Lo, Andrew TI Unintended Consequences of Expensive Cancer Therapeutics-The Pursuit of Marginal Indications and a Me-Too Mentality That Stifles Innovation and Creativity The John Conley Lecture SO JAMA OTOLARYNGOLOGY-HEAD & NECK SURGERY LA English DT Article ID CELL LUNG-CANCER; PHASE-III TRIAL; METASTATIC COLORECTAL-CANCER; ADVANCED BREAST-CANCER; GASTROINTESTINAL STROMAL TUMORS; IXABEPILONE PLUS CAPECITABINE; MEDULLARY-THYROID CANCER; PROSTATE-CANCER; OPEN-LABEL; DOUBLE-BLIND AB Cancer is expected to continue as a major health and economic problem worldwide. Several factors are contributing to the increasing economic burden imposed by cancer, with the cost of cancer drugs an undeniably important variable. The use of expensive therapies with marginal benefits for their approved indications and for unproven indications is contributing to the rising cost of cancer care. We believe that expensive therapies are stifling progress by (1) encouraging enormous expenditures of time, money, and resources on marginal therapeutic indications and (2) promoting a me-too mentality that is stifling innovation and creativity. The modest gains of Food and Drug Administration-approved therapies and the limited progress against major cancers is evidence of a lowering of the efficacy bar that, together with high drug prices, has inadvertently incentivized the pursuit of marginal outcomes and a me-too mentality evidenced by the duplication of effort and redundant pharmaceutical pipelines. We discuss the economic realities that are driving this process and provide suggestions for radical changes to reengineer our collective cancer ecosystem to achieve better outcomes for society. C1 [Fojo, Tito; Mailankody, Sham] NCI, Ctr Canc Res, Bethesda, MD 20892 USA. [Lo, Andrew] MIT, Sloan Sch Management, Cambridge, MA 02139 USA. RP Fojo, T (reprint author), NCI, Ctr Canc Res, 9000 Rockville Pike,Bldg 10,Rm 12N226, Bethesda, MD 20892 USA. EM fojot@mail.nih.gov NR 113 TC 53 Z9 53 U1 3 U2 20 PU AMER MEDICAL ASSOC PI CHICAGO PA 330 N WABASH AVE, STE 39300, CHICAGO, IL 60611-5885 USA SN 2168-6181 EI 2168-619X J9 JAMA OTOLARYNGOL JI JAMA Otolaryngol-Head Neck Surg. PD DEC PY 2014 VL 140 IS 12 BP 1225 EP 1236 DI 10.1001/jamaoto.2014.1570 PG 12 WC Otorhinolaryngology; Surgery SC Otorhinolaryngology; Surgery GA AX0JC UT WOS:000346637700017 PM 25068501 ER PT J AU Fuhrman, BJ Feigelson, HS Flores, R Gail, MH Xu, X Ravel, J Goedert, JJ AF Fuhrman, Barbara J. Feigelson, Heather Spencer Flores, Roberto Gail, Mitchell H. Xu, Xia Ravel, Jacques Goedert, James J. TI Associations of the Fecal Microbiome With Urinary Estrogens and Estrogen Metabolites in Postmenopausal Women SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article ID BREAST-CANCER RISK; MASS SPECTROMETRY METHOD; NECROSIS-FACTOR-ALPHA; CORE GUT MICROBIOME; ESTRADIOL METABOLISM; MENOPAUSAL WOMEN; OBESITY; HORMONES; DETERMINANTS; EXCRETION AB Context: Thegut microbiota may influence the risk of breast cancer through effects on endogenous estrogens. Objective: The objective of the study was to investigate whether urinary estrogens and estrogen metabolites are associated with the diversity and composition of the fecal microbiome. Design and Setting: This was a cross-sectional study among women enrolled in Kaiser Permanente of Colorado. Participants: A total of 60 women drawn from a random sample of healthy postmenopausal women (aged 55-69 y), without current or recent use of antibiotics or hormone therapy and no history of cancer or gastrointestinal disease participated in the study. Outcome Measures and Methods: Creatinine-standardized urinary estrogens (estrone and estradiol) and 13 hydroxylated estrogen metabolites were measured in spot urines by liquid chromatography-tandem mass spectrometry. The fecal microbiome was assessed using pyrosequencing of 16S rRNA amplicons. General linear models were used to test for associations of diversity and composition of the fecal microbiome with parent estrogen (estrone + estradiol), total estrogens, and estrogen metabolites and the ratio of estrogen metabolites to parent estrogen, which has been predictive of postmenopausal breast cancer risk in previous studies. Results: The ratio of metabolites to parents was directly associated with whole-tree phylogenetic diversity (R = 0.35, P = .01 ). Relative abundances of the order Clostridiales (R = 0.32, P = .02) and the genus Bacteroides (R = -0.30, P = .03) were also correlated with the ratio of metabolites to parents. Associations were independent of age, body mass index, and study design factors. Conclusions: Ourdata suggest that women with a more diverse gut microbiome exhibit an elevated urinary ratio of hydroxylated estrogen metabolites to parent estrogen. Further research is warranted to confirm and relate these findings to clinical disease. C1 [Fuhrman, Barbara J.] Univ Arkansas Med Sci, Fay W Boozman Coll Publ Hlth, Dept Epidemiol, Little Rock, AR 72205 USA. [Fuhrman, Barbara J.; Flores, Roberto; Gail, Mitchell H.; Goedert, James J.] NCI, Div Canc Epidemiol & Genet, NIH, Dept Hlth & Human Serv, Bethesda, MD 20892 USA. [Flores, Roberto] NCI, Canc Prevent Div, NIH, Dept Hlth & Human Serv, Bethesda, MD 20892 USA. [Feigelson, Heather Spencer] Kaiser Permanente Colorado, Inst Hlth Res, Denver, CO 80231 USA. [Xu, Xia] Leidos Biomed Res Inc, Canc Res Technol Program, Frederick Natl Lab Canc Res, Frederick, MD 21702 USA. [Ravel, Jacques] Univ Maryland, Inst Genome Sci, Baltimore, MD 21201 USA. RP Goedert, JJ (reprint author), NCI, Div Canc Epidemiol, NIH, Dept Hlth & Human Serv, 9609 Med Ctr Dr,Room 6E106,MSC 9767, Bethesda, MD 20892 USA. EM goedertj@mail.nih.gov OI Fuhrman, Barbara/0000-0002-1777-9888; Ravel, Jacques/0000-0002-0851-2233 FU Intramural Research Program of the NCI; National Institutes of Health; National Cancer Institute Intramural Research Program [HHSN261200800001E] FX This research was supported by the Intramural Research Program of the NCI, National Institutes of Health, but this support did not influence the data analysis, manuscript preparation, or decision to submit for publication.; This work was supported in whole or in part by federal funds from the National Cancer Institute Intramural Research Program under Contract HHSN261200800001E. NR 40 TC 11 Z9 13 U1 7 U2 27 PU ENDOCRINE SOC PI WASHINGTON PA 2055 L ST NW, SUITE 600, WASHINGTON, DC 20036 USA SN 0021-972X EI 1945-7197 J9 J CLIN ENDOCR METAB JI J. Clin. Endocrinol. Metab. PD DEC PY 2014 VL 99 IS 12 BP 4632 EP 4640 DI 10.1210/jc.2014-2222 PG 9 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA AX1ZP UT WOS:000346743300035 PM 25211668 ER PT J AU Crocker, MK Gourgari, E Lodish, M Stratakis, CA AF Crocker, Melissa K. Gourgari, Evgenia Lodish, Maya Stratakis, Constantine A. TI Use of Aromatase Inhibitors in Large Cell Calcifying Sertoli Cell Tumors: Effects on Gynecomastia, Growth Velocity, and Bone Age SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article ID PEUTZ-JEGHERS-SYNDROME; PREPUBERTAL GYNECOMASTIA; CARNEY COMPLEX; FEATURES; TESTIS AB Context: Large cell calcifying Sertoli cell tumors (LCCSCT) present in isolation or, especially in children, in association with Carney Complex (CNC) or Peutz- Jeghers Syndrome (PJS). These tumors overexpress aromatase (CYP19A1), which leads to increased conversion of delta-4-androstenedi-one to estrone and testosterone to estradiol. Prepubertal boys may present with growth acceleration, advanced bone age, and gynecomastia. Objective: To investigate the outcomes of aromatase inhibitor therapy (AIT) in prepubertal boys with LCCSCTs. Design: Case series of a very rare tumor and chart review of cases treated at other institutions. Setting: Tertiary care and referral center. Patients: Six boys, five with PJS and one with CNC, were referred to the National Institutes of Health for treatment of LCCSCT. All patients had gynecomastia, testicular enlargement, and advanced bone ages, and were being treated by their referring physicians with AIT. Interventions: Patients were treated for a total of 6-60 months on AIT. Main Outcome Measures: Height, breast tissue mass, and testicular size were all followed; physical examination, scrotal ultrasounds, and bone ages were obtained, and hormonal concentrations and tumor markers were measured. Results: Tumor markers were negative. All patients had decreases in breast tissue while on therapy. Height percentiles declined, and predicted adult height moved closer to midparental height as bone age advancement slowed. Testicular enlargement stabilized until entry into central puberty. Only one patient required unilateral orchiectomy. Conclusions: Patients with LCCSCT benefit from AIT with reduction and/or elimination of gynecomastia and slowing of linear growth and bone age advancement. Further study of long-term outcomesandsafety monitoring areneededbut these preliminary data suggest thatmammoplasty and/or orchiectomy may be foregone in light of the availability of medical therapy. C1 [Crocker, Melissa K.; Gourgari, Evgenia; Lodish, Maya; Stratakis, Constantine A.] NIH, Sect Endocrinol & Genet, Program Dev Endocrinol & Genet, Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Bethesda, MD 20892 USA. [Crocker, Melissa K.] Boston Childrens Hosp, Div Endocrinol, Boston, MA 02115 USA. [Gourgari, Evgenia] Georgetown Univ, Div Pediat Endocrinol, Washington, DC 20007 USA. RP Lodish, M (reprint author), Bg 10-CRC Room 1-3330,10 Ctr Dr, Bethesda, MD 20814 USA. EM lodishma@mail.nih.gov FU Intramural Research Programs of The Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD); National Institutes of Health Clinical Center FX This work was supported by The Intramural Research Programs of The Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) and the National Institutes of Health Clinical Center. NR 21 TC 2 Z9 2 U1 0 U2 2 PU ENDOCRINE SOC PI WASHINGTON PA 2055 L ST NW, SUITE 600, WASHINGTON, DC 20036 USA SN 0021-972X EI 1945-7197 J9 J CLIN ENDOCR METAB JI J. Clin. Endocrinol. Metab. PD DEC PY 2014 VL 99 IS 12 BP E2673 EP E2680 DI 10.1210/jc.2014-2530 PG 8 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA AX1ZP UT WOS:000346743300076 PM 25226294 ER PT J AU Ma, YHV Schwartz, AV Sigurdsson, S Hue, TF Lang, TF Harris, TB Rosen, CJ Vittinghoff, E Eiriksdottir, G Hauksdottir, AM Siggeirsdottir, K Sigurdsson, G Oskarsdottir, D Napoli, N Palermo, L Gudnason, V Li, XJ AF Ma, Yu-Heng Vivian Schwartz, Ann V. Sigurdsson, Sigurdur Hue, Trisha F. Lang, Thomas F. Harris, Tamara B. Rosen, Clifford J. Vittinghoff, Eric Eiriksdottir, Gudny Hauksdottir, Alda M. Siggeirsdottir, Kristin Sigurdsson, Gunnar Oskarsdottir, Diana Napoli, Nicola Palermo, Lisa Gudnason, Vilmundur Li, Xiaojuan TI Circulating Sclerostin Associated With Vertebral Bone Marrow Fat in Older Men But Not Women SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article ID SERUM SCLEROSTIN; MINERAL DENSITY; POSTMENOPAUSAL WOMEN; FRACTURE; ADULTS; MASS; ADIPOGENESIS; OSTEOPOROSIS; PERFUSION; STRENGTH AB Context: Osteocyte activity is crucial to the maintenance of bone quality. Sclerostin, an osteocyte product, inhibits bone formation, yet higher circulating sclerostin is associated with higher bone density. Bone marrow fat (MF) is associated with osteoporosis, but little is known about the relationship between osteocyte activity and MF. Objective: Our objective was to assess the relationships between circulating sclerostin, vertebral MF, volumetric bone mineral density (vBMD), and other fat depots in older adults. Design, Setting, and Participants: We conducted a cross-sectional study in the Age Gene/Environment Susceptibility-Reykjavik cohort. Main Outcome Measures: Outcome measures included vertebral MF (L1-L4) measured with magnetic resonance spectroscopy and vBMD (spine and hip) and abdominal fat measured with quantitative computed tomography. Results: After excluding subjects with bone-active medication use (n = 50), inadequate serum (n = 2), or inadequate magnetic resonance spectroscopy (n = 1), analyses included 115 men and 134 women (mean age 79 y, mean body mass index 27.7 kg/m(2)). In men, but not women, vertebral MF was greater in those with higher serum sclerostin levels. MF was 52.2% in the lowest tertile of serum sclerostin and 56.3% in the highest tertile in men (P for trend <.01) in models adjusted for age, body mass index, and diabetes. Sclerostin was positively associated with cortical and trabecular total hip vBMD, weight in men and women, and total fat mass in men but was not associated with total lean mass or abdominal fat depots. Conclusion: Circulating sclerostin levels are associated with higher vertebral marrow fat in men, suggesting a relationship between osteocyte function and marrow adipogenesis. C1 [Ma, Yu-Heng Vivian; Schwartz, Ann V.; Hue, Trisha F.; Lang, Thomas F.; Vittinghoff, Eric; Palermo, Lisa; Li, Xiaojuan] Univ Calif San Francisco, San Francisco, CA 94107 USA. [Sigurdsson, Sigurdur; Eiriksdottir, Gudny; Hauksdottir, Alda M.; Siggeirsdottir, Kristin; Oskarsdottir, Diana; Gudnason, Vilmundur] Iceland Heart Assoc, IS-201 Kopavogur, Iceland. [Harris, Tamara B.] NIA, Lab Epidemiol Demog & Biometry, Intramural Res Program, Bethesda, MD 20892 USA. [Rosen, Clifford J.] Maine Med Ctr Res Inst, Scarborough, ME 04074 USA. [Sigurdsson, Gunnar; Oskarsdottir, Diana; Gudnason, Vilmundur] Univ Iceland, Fac Med, IS-101 Reykjavik, Iceland. [Sigurdsson, Gunnar] Landspitali Univ Hosp, Dept Endocrinol & Metab, IS-101 Reykjavik, Iceland. [Napoli, Nicola] Univ Campus Bio Med, I-00128 Rome, Italy. RP Schwartz, AV (reprint author), Univ Calif San Francisco, 185 Berry St,Lobby 5,Suite 5700, San Francisco, CA 94107 USA. EM aschwartz@psg.ucsf.edu RI Gudnason, Vilmundur/K-6885-2015; OI Gudnason, Vilmundur/0000-0001-5696-0084; Napoli, Nicola/0000-0002-3091-8205 FU National Institute of Arthritis and Musculoskeletal and Skin Diseases [R01AR057819]; National Institutes of Health [N01-AG-12100]; National Institute on Aging Intramural Research Program, Hjartavernd (The Icelandic Heart Association); Althingi (The Icelandic Parliament); National Institute of Diabetes and Digestive and Kidney Diseases [R24DK092759] FX The ancillary study was supported by the National Institute of Arthritis and Musculoskeletal and Skin Diseases (Grant R01AR057819). The AGES Reykjavik Study is supported by funding from the National Institutes of Health (Contract N01-AG-12100), the National Institute on Aging Intramural Research Program, Hjartavernd (The Icelandic Heart Association), and the Althingi (The Icelandic Parliament). C.J.R. received support from the National Institute of Diabetes and Digestive and Kidney Diseases (Grant R24DK092759). NR 31 TC 11 Z9 12 U1 1 U2 3 PU ENDOCRINE SOC PI WASHINGTON PA 2055 L ST NW, SUITE 600, WASHINGTON, DC 20036 USA SN 0021-972X EI 1945-7197 J9 J CLIN ENDOCR METAB JI J. Clin. Endocrinol. Metab. PD DEC PY 2014 VL 99 IS 12 BP E2584 EP E2590 DI 10.1210/jc.2013-4493 PG 7 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA AX1ZP UT WOS:000346743300065 PM 25144629 ER PT J AU Moustgaard, H Bello, S Miller, FG Hrobjartsson, A AF Moustgaard, Helene Bello, Segun Miller, Franklin G. Hrobjartsson, Asbjorn TI Subjective and objective outcomes in randomized clinical trials: definitions differed in methods publications and were often absent from trial reports SO JOURNAL OF CLINICAL EPIDEMIOLOGY LA English DT Review DE Subjective outcomes; Objective outcomes; Types of outcomes; Endpoints; Risk of bias; Randomized clinical trials ID OBSERVER BIAS; ASSESSORS; AUTHORS AB Objectives: The degree of bias in randomized clinical trials varies depending on whether the outcome is subjective or objective. Assessment of the risk of bias in a clinical trial will therefore often involve categorization of the type of outcome. Our primary aim was to examine how the concepts "subjective outcome" and "objective outcome" are defined in methodological publications and clinical trial reports. To put this examination into perspective, we also provide an overview of how outcomes are classified more broadly. Study Design and Setting: A systematic review of methodological publications providing a classification of clinical trial outcomes and a descriptive study of how outcomes were classified in 200 PubMed indexed clinical trial reports published in 2012. Results: We identified 90 methodological publications with some form of a classification of outcomes. Three distinct definitions were provided for subjective outcome: (1) dependent on assessor judgment, (2) patient-reported outcome, or (3) private phenomena (ie, phenomena only assessable by the patient). Of the 200 clinical trial reports, 12 used the term "subjective" and/or "objective" about outcomes, but no clinical trial reports explicitly defined the terms. Conclusion: The terms "subjective" and "objective" are ambiguous when used to describe outcomes in randomized clinical trials. We suggest that the terms should be defined explicitly when used in connection with the assessment of risk of bias in a clinical trial, in meta-epidemiological research, and generally in the reporting of clinical trials. We also suggest that adding an explicit clarification of the terms in future versions of the Cochrane Handbook might further strengthen its important role in guiding review authors. (C) 2014 Elsevier Inc. All rights reserved. C1 [Moustgaard, Helene; Bello, Segun; Hrobjartsson, Asbjorn] Rigshosp, Nord Cochrane Ctr, DK-2100 Copenhagen O, Denmark. [Miller, Franklin G.] NIH, Dept Bioeth, Bethesda, MD 20892 USA. RP Moustgaard, H (reprint author), Rigshosp, Nord Cochrane Ctr, Dept 7811,Blegdamsvej 9, DK-2100 Copenhagen O, Denmark. EM helene.moustgaard@gmail.com NR 26 TC 5 Z9 5 U1 2 U2 5 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0895-4356 EI 1878-5921 J9 J CLIN EPIDEMIOL JI J. Clin. Epidemiol. PD DEC PY 2014 VL 67 IS 12 BP 1327 EP 1334 DI 10.1016/j.jclinepi.2014.06.020 PG 8 WC Health Care Sciences & Services; Public, Environmental & Occupational Health SC Health Care Sciences & Services; Public, Environmental & Occupational Health GA AX4DI UT WOS:000346883700008 PM 25263546 ER PT J AU Ning, J Qin, J Shen, Y AF Ning, Jing Qin, Jing Shen, Yu TI Score Estimating Equations from Embedded Likelihood Functions Under Accelerated Failure Time Model SO JOURNAL OF THE AMERICAN STATISTICAL ASSOCIATION LA English DT Article DE Cox model; Length-biased data; Proportional odds model; Score equation ID RIGHT-CENSORED DATA; LARGE-SAMPLE THEORY; LINEAR RANK-TESTS; EMPIRICAL DISTRIBUTIONS; REGRESSION-ANALYSIS; PREVALENT COHORT; SURVIVAL; INFERENCE AB The semiparametric accelerated failure time (AFT) model is one of the most popular models for analyzing time-to-event outcomes. One appealing feature of the AFT model is that the observed failure time data can be transformed to identically independent distributed random variables without covariate effects. We describe a class of estimating equations based on the score functions for the transformed data, which are derived from the full likelihood function under commonly used semiparametric models such as the proportional hazards or proportional odds model. The methods of estimating regression parameters under the AFT model can be applied to traditional right-censored survival data as well as more complex time-to-event data subject to length-biased sampling. We establish the asymptotic properties and evaluate the small sample performance of the proposed estimators. We illustrate the proposed methods through applications in two examples. C1 [Ning, Jing; Shen, Yu] Univ Texas MD Anderson Canc Ctr, Dept Biostat, Houston, TX 77030 USA. [Qin, Jing] NIAID, Biostat Res Branch, Bethesda, MD 20817 USA. RP Ning, J (reprint author), Univ Texas MD Anderson Canc Ctr, Dept Biostat, Houston, TX 77030 USA. EM jning@mdanderson.edu; jingqin@niaid.nih.gov; yshen@mdanderson.org FU National Institutes of Health [CA079466, CA016672]; Seniors' Independence Research Program through the National Health Research and Development Program of Health Canada [6606-3954-MC(S)]; Pfizer Canada Incorporated through Medical Research Council/Pharmaceutical Manufacturers Association of Canada Health Activity Program, NHRDP [6603-1417-302(R)]; Bayer Incorporated; British Columbia Health Research Foundation [38 (93-2), 34 (96-1)] FX This work was supported in part by grants CA079466 and CA016672 from the National Institutes of Health. The authors are grateful to Professor M. Asgharian and investigators from the Canadian Study of Health and Aging for providing us with the dementia data. The data reported in the example were collected as part of the CSHA. The core study was funded by the Seniors' Independence Research Program through the National Health Research and Development Program of Health Canada (Project no. 6606-3954-MC(S)). Additional funding was provided by Pfizer Canada Incorporated through the Medical Research Council/Pharmaceutical Manufacturers Association of Canada Health Activity Program, NHRDP Project 6603-1417-302(R), Bayer Incorporated, and the British Columbia Health Research Foundation Projects 38 (93-2) and 34 (96-1). The study was coordinated through the University of Ottawa and the Division of Aging and Seniors, Health Canada. NR 36 TC 2 Z9 2 U1 2 U2 7 PU AMER STATISTICAL ASSOC PI ALEXANDRIA PA 732 N WASHINGTON ST, ALEXANDRIA, VA 22314-1943 USA SN 0162-1459 EI 1537-274X J9 J AM STAT ASSOC JI J. Am. Stat. Assoc. PD DEC PY 2014 VL 109 IS 508 BP 1625 EP 1635 DI 10.1080/01621459.2014.946034 PG 11 WC Statistics & Probability SC Mathematics GA AX2TI UT WOS:000346797000024 PM 25663727 ER PT J AU Li, Y Arao, Y Hall, JM Burkett, S Liu, LW Gerrish, K Cavailles, V Korach, KS AF Li, Yin Arao, Yukitomo Hall, Julie M. Burkett, Sandra Liu, Liwen Gerrish, Kevin Cavailles, Vincent Korach, Kenneth S. TI Research Resource: STR DNA Profile and Gene Expression Comparisons of Human BG-1 Cells and a BG-1/MCF-7 Clonal Variant SO MOLECULAR ENDOCRINOLOGY LA English DT Article ID OVARIAN-CANCER CELLS; ESTROGEN-RECEPTOR-BETA; ENDOCRINE DISRUPTING CHEMICALS; MESSENGER-RIBONUCLEIC-ACID; HUMAN-BREAST-CANCER; ALPHA ER-ALPHA; DOWN-REGULATION; LINE; FIBULIN-1; ESTRADIOL AB Human ovarian cancer BG-1 cells are a valuable in vitro model that has enabled several laboratories to study the estrogenic responses of ovarian cancers. We recently discovered that there are two different BG-1 cell lines being used for experiments, denoted here as BG-1 FR and BG-1 NIEHS, which exhibit striking morphological differences. The objective of this study was to methodically analyze these two BG-1 variants and compare their characteristics. Short tandem repeat analysis revealed that the DNA profile of BG-1 FR cells was unique, yet the Short tandem repeat pattern of BG-1 NIEHS was identical with that of MCF-7 cells. From a cytogenetic analysis, it became apparent that the BG-1 FR line had the same profile as previously reported, whereas the BG-1 NIEHS and MCF-7 cells share a similar genetic display. A significant number of unique chromosomal translocations were observed between the BG-1 NIEHS and MCF-7 cells, suggesting that acquired genotypic differences resulted in the formation of two lines from a common origin. Although all cell types demonstrated a similar estrogen responsiveness in reporter gene assays, a microarray analysis revealed distinct estrogen-responsive gene expression patterns with surprisingly moderate to low overlap. We conclude that BG-1 FR is the original ovarian cancer cell line, whereas the BG-1 NIEHS is a variant from the MCF-7 cells. These findings provide much needed clarification of the identities and characteristics of key cell line models that are widely used to study estrogen action in female reproductive cancers. C1 [Li, Yin; Arao, Yukitomo; Korach, Kenneth S.] NIEHS, Reprod & Dev Toxicol Lab, NIH, Res Triangle Pk, NC 27709 USA. [Liu, Liwen; Gerrish, Kevin] NIEHS, Mol Genom Core Facil, NIH, Res Triangle Pk, NC 27709 USA. [Hall, Julie M.] Campbell Univ, Coll Pharm & Hlth Sci, Buies Creek, NC 27506 USA. [Burkett, Sandra] NCI, Ctr Canc Res, NIH, Frederick, MD 21702 USA. [Cavailles, Vincent] Univ Montpellier I, Inst Rech Cancerol Montpellier, F-34298 Montpellier, France. [Cavailles, Vincent] Univ Montpellier I, INSERM, Unite 896, F-34298 Montpellier, France. RP Korach, KS (reprint author), NIEHS, Reprod & Dev Toxicol Lab, NIH, 111 Alexander Dr,POB 12233, Res Triangle Pk, NC 27709 USA. EM korach@niehs.nih.gov OI Korach, Kenneth/0000-0002-7765-418X FU Division of Intramural Research of the National Institute of Environmental Health Sciences [Z01 ES70065] FX This work was supported by the Division of Intramural Research of the National Institute of Environmental Health Sciences through Grant Z01 ES70065 (to K.S.K.). NR 48 TC 2 Z9 2 U1 2 U2 5 PU ENDOCRINE SOC PI WASHINGTON PA 2055 L ST NW, SUITE 600, WASHINGTON, DC 20036 USA SN 0888-8809 J9 MOL ENDOCRINOL JI Mol. Endocrinol. PD DEC PY 2014 VL 28 IS 12 BP 2072 EP 2081 DI 10.1210/me.2014-1229 PG 10 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA AX3KC UT WOS:000346837200015 PM 25321415 ER PT J AU Polotow, TG Vardaris, CV Mihaliuc, AR Goncalves, MS Pereira, B Ganini, D Barros, MP AF Polotow, Tatiana G. Vardaris, Cristina V. Mihaliuc, Andrea R. Goncalves, Marina S. Pereira, Benedito Ganini, Douglas Barros, Marcelo P. TI Astaxanthin Supplementation Delays Physical Exhaustion and Prevents Redox Imbalances in Plasma and Soleus Muscles of Wistar Rats SO NUTRIENTS LA English DT Article DE carotenoid; exercise; iron; uric acid; oxidative stress; mitochondria ID OXIDATIVE STRESS; SKELETAL-MUSCLE; LIQUID-CHROMATOGRAPHY; TISSUE DISTRIBUTION; LIPID-METABOLISM; FREE-RADICALS; HUMAN HEALTH; EXERCISE; GLUTATHIONE; FATIGUE AB Astaxanthin (ASTA) is a pinkish-orange carotenoid commonly found in marine organisms, especially salmon. ASTA is a powerful antioxidant and suggested to provide benefits for human health, including the inhibition of LDL oxidation, UV-photoprotection, and prophylaxis of bacterial stomach ulcers. Exercise is associated to overproduction of free radicals in muscles and plasma, with pivotal participation of iron ions and glutathione (GSH). Thus, ASTA was studied here as an auxiliary supplement to improve antioxidant defenses in soleus muscles and plasma against oxidative damage induced by exhaustive exercise. Long-term 1 mg ASTA/kg body weight (BW) supplementation in Wistar rats (for 45 days) significantly delayed time to exhaustion by 29% in a swimming test. ASTA supplementation increased scavenging/iron-chelating capacities (TEAC/FRAP) and limited exercise-induced iron overload and its related pro-oxidant effects in plasma of exercising animals. On the other hand, ASTA induced significant mitochondrial Mn-dependent superoxide dismutase and cytosolic glutathione peroxidase antioxidant responses in soleus muscles that, in turn, increased GSH content during exercise, limited oxidative stress, and delayed exhaustion. We also provided significant discussion about a putative "mitochondrial-targeted" action of ASTA based on previous publications and on the positive results found in the highly mitochondrial populated (oxidative-type) soleus muscles here. C1 [Polotow, Tatiana G.; Vardaris, Cristina V.; Mihaliuc, Andrea R.; Goncalves, Marina S.; Ganini, Douglas; Barros, Marcelo P.] Univ Cruzeiro Sul, Inst Phys Act & Sports Sci ICAFE, BR-01506000 Sao Paulo, Brazil. [Pereira, Benedito] Univ Sao Paulo, Sch Phys Educ & Sports EEFE, BR-05508900 Sao Paulo, Brazil. [Ganini, Douglas] NIEHS, Free Rad Metab Grp, Lab Toxicol & Pharmacol, Durham, NC 27709 USA. RP Barros, MP (reprint author), Univ Cruzeiro Sul, Inst Phys Act & Sports Sci ICAFE, BR-01506000 Sao Paulo, Brazil. EM tatianapolotow@hotmail.com; crisvardaris@gmail.com; andreamihaliuc@hotmail.com; masg_je@yahoo.com.br; benepe@usp.br; douganini@uol.com.br; marcelo.barros@cruzeirodosul.edu.br RI Barros, Marcelo/K-1410-2013 OI Barros, Marcelo/0000-0003-3565-8331 FU Fundacao de Amparo a Pesquisa do Estado de Sao Paulo [FAPESP 2009/12342-8]; Conselho Nacional de Desenvolvimento Cientifico e Tecnologico (Bolsa Produtividade em Pesquisa, Nivel 2, CNPq, Brazil) [307474/2012-7]; Programa de Suporte a Pos-Graduacao de Instituicoes de Ensino Particulares (PROSUP/CAPES); CYTED (Spain, EU) [112RT0445] FX The authors are indebted to the Brazilian funding agencies Fundacao de Amparo a Pesquisa do Estado de Sao Paulo (FAPESP 2009/12342-8), Conselho Nacional de Desenvolvimento Cientifico e Tecnologico (Bolsa Produtividade em Pesquisa, Nivel 2, #307474/2012-7, CNPq, Brazil), and the Programa de Suporte a Pos-Graduacao de Instituicoes de Ensino Particulares (PROSUP/CAPES). The authors, Tatiana G. Polotow, Cristina V. Vardaris, and Marcelo P. Barros are members of the IBERCAROT network, funded by CYTED (ref. 112RT0445, Spain, EU). The authors are also indebted to Gustavo Egea Gallucci, Marilia Cerqueira Leite Seelaender and Rui Curi, from Institute of Biological Sciences (ICB/USP), University of Sao Paulo, and Etelvino J. H. Bechara, from Federal University of Sao Paulo (UNIFESP-Diadema) for experimental and equipment support. Marcelo Paes de Barros is also indebted to Ake Lignell, CEO and Marketing Director of AstaReal AB (Gustavsberg, Sweden) for donating astaxanthin-rich algal biomass for animal supplementation in our study. NR 57 TC 4 Z9 7 U1 5 U2 23 PU MDPI AG PI BASEL PA POSTFACH, CH-4005 BASEL, SWITZERLAND SN 2072-6643 J9 NUTRIENTS JI Nutrients PD DEC PY 2014 VL 6 IS 12 BP 5819 EP 5838 DI 10.3390/nu6125819 PG 20 WC Nutrition & Dietetics SC Nutrition & Dietetics GA AX2TA UT WOS:000346796100028 PM 25514562 ER PT J AU Jacobson, KA Costanzi, S Paolettal, S AF Jacobson, Kenneth A. Costanzi, Stefano Paolettal, Silvia TI Computational studies to predict or explain G protein coupled receptor polypharmacology SO TRENDS IN PHARMACOLOGICAL SCIENCES LA English DT Review DE G protein-coupled receptors; molecular modeling; bioinformatics; chemoinformatics ID STRUCTURE-BASED DISCOVERY; LIGAND DISCOVERY; DRUG DISCOVERY; CRYSTAL-STRUCTURE; HOMOLOGY MODELS; IN-SILICO; ANTAGONISTS; DOCKING; GENOME; CRYSTALLOGRAPHY AB Since G protein-coupled receptors (GPCRs) belong to a very large superfamily of evolutionarily related receptors (>800 members in humans), and due to the rapid progress on their structural biology, they are ideal candidates for polypharmacology studies. Broad screening and bioinformatics/chemoinformatics have been applied to understanding off-target effects of GPCR ligands. It is now feasible to approach the question of GPCR polypharmacology using molecular modeling and the available X-ray GPCR structures. As an example, large and sterically constrained adenosine derivatives (potent adenosine receptor ligands with low conformational freedom and multiple extended substituents) were screened for binding at diverse receptors. Unanticipated off-target interactions, including at biogenic amine receptors, were then modeled using a structure-based approach to provide a consistent understanding of recognition. A conserved Asp in TM3 changed its role from counterion for biogenic amines to characteristic H-bonding to adenosine. The same systematic approach could potentially be applied to many GPCRs or other receptors using other sets of congeneric ligands. C1 [Jacobson, Kenneth A.; Paolettal, Silvia] NIDDK, Mol Recognit Sect, Bioorgan Chem Lab, NIH, Bethesda, MD 20892 USA. [Costanzi, Stefano] Amer Univ, Dept Chem, Washington, DC 20016 USA. [Costanzi, Stefano] Amer Univ, Ctr Behav Neurosci, Washington, DC 20016 USA. RP Jacobson, KA (reprint author), NIDDK, Mol Recognit Sect, Bioorgan Chem Lab, NIH, Bethesda, MD 20892 USA. EM kennethj@helix.nih.gov RI Jacobson, Kenneth/A-1530-2009 OI Jacobson, Kenneth/0000-0001-8104-1493 FU Intramural NIH HHS [Z99 DK999999, ZIA DK031126-08] NR 58 TC 11 Z9 11 U1 3 U2 21 PU ELSEVIER SCIENCE LONDON PI LONDON PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND SN 0165-6147 J9 TRENDS PHARMACOL SCI JI Trends Pharmacol. Sci. PD DEC PY 2014 VL 35 IS 12 BP 658 EP 663 DI 10.1016/j.tips.2014.10.009 PG 6 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA AX4HS UT WOS:000346894700008 PM 25458540 ER PT J AU Duignan, PJ Van Bressem, MF Baker, JD Barbieri, M Colegrove, KM De Guise, S de Swart, RL Di Guardo, G Dobson, A Duprex, WP Early, G Fauquier, D Goldstein, T Goodman, SJ Grenfell, B Groch, KR Gulland, F Hall, A Jensen, BA Lamy, K Matassa, K Mazzariol, S Morris, SE Nielsen, O Rotstein, D Rowles, TK Saliki, JT Siebert, U Waltzek, T Wellehan, JFX AF Duignan, Padraig J. Van Bressem, Marie-Francoise Baker, Jason D. Barbieri, Michelle Colegrove, Kathleen M. De Guise, Sylvain de Swart, Rik L. Di Guardo, Giovanni Dobson, Andrew Duprex, W. Paul Early, Greg Fauquier, Deborah Goldstein, Tracey Goodman, Simon J. Grenfell, Bryan Groch, Katia R. Gulland, Frances Hall, Ailsa Jensen, Brenda A. Lamy, Karina Matassa, Keith Mazzariol, Sandro Morris, Sinead E. Nielsen, Ole Rotstein, David Rowles, Teresa K. Saliki, Jeremy T. Siebert, Ursula Waltzek, Thomas Wellehan, James F. X. TI Phocine Distemper Virus: Current Knowledge and Future Directions SO VIRUSES-BASEL LA English DT Review DE Morbillivirus; pinnipeds; sea otter; CD150/SLAM; phylogeny; pathology; epidemiology; immunity; vaccine ID EUROPEAN HARBOR SEALS; OTTERS ENHYDRA-LUTRIS; SCOTTISH GREY SEALS; HAWAIIAN MONK SEAL; CANINE-DISTEMPER; MEASLES-VIRUS; HALICHOERUS-GRYPUS; MORBILLIVIRUS INFECTION; MASS MORTALITY; CETACEAN MORBILLIVIRUS AB Phocine distemper virus (PDV) was first recognized in 1988 following a massive epidemic in harbor and grey seals in north-western Europe. Since then, the epidemiology of infection in North Atlantic and Arctic pinnipeds has been investigated. In the western North Atlantic endemic infection in harp and grey seals predates the European epidemic, with relatively small, localized mortality events occurring primarily in harbor seals. By contrast, PDV seems not to have become established in European harbor seals following the 1988 epidemic and a second event of similar magnitude and extent occurred in 2002. PDV is a distinct species within the Morbillivirus genus with minor sequence variation between outbreaks over time. There is now mounting evidence of PDV-like viruses in the North Pacific/Western Arctic with serological and molecular evidence of infection in pinnipeds and sea otters. However, despite the absence of associated mortality in the region, there is concern that the virus may infect the large Pacific harbor seal and northern elephant seal populations or the endangered Hawaiian monk seals. Here, we review the current state of knowledge on PDV with particular focus on developments in diagnostics, pathogenesis, immune response, vaccine development, phylogenetics and modeling over the past 20 years. C1 [Duignan, Padraig J.; Lamy, Karina] Univ Calgary, Dept Ecosyst & Publ Hlth, Calgary, AB T2N 4Z6, Canada. [Van Bressem, Marie-Francoise] Peruvian Ctr Cetacean Res CEPEC, Cetacean Conservat Med Grp CMED, Lima 20, Peru. [Baker, Jason D.; Barbieri, Michelle] NOAA, Natl Marine Fisheries Serv, Pacific Isl Fisheries Sci Ctr, Honolulu, HI 96818 USA. [Barbieri, Michelle; Gulland, Frances] Marine Mammal Ctr, Sausalito, CA 94965 USA. [Colegrove, Kathleen M.] Univ Illinois, Coll Vet Med, Zool Pathol Program, Maywood, IL 60153 USA. [De Guise, Sylvain] Univ Connecticut, Dept Pathobiol & Vet Sci, Storrs, CT 06269 USA. [De Guise, Sylvain] Univ Connecticut, Connecticut Sea Grant Coll Program, Storrs, CT 06269 USA. [de Swart, Rik L.] Erasmus MC, Dept Virosci, NL-3015 CN Rotterdam, Netherlands. [Di Guardo, Giovanni] Univ Teramo, Fac Vet Med, I-64100 Teramo, Italy. [Dobson, Andrew; Grenfell, Bryan; Morris, Sinead E.] Princeton Univ, Dept Ecol & Evolutionary Biol, Princeton, NJ 08544 USA. [Duprex, W. Paul] Boston Univ, Sch Med, Dept Microbiol, Boston, MA 02118 USA. [Early, Greg] Integrated Stat, Woods Hole, MA 02543 USA. [Fauquier, Deborah; Rowles, Teresa K.] NOAA, Natl Marine Fisheries Serv, Marine Mammal Hlth & Stranding Response Program, Silver Spring, MD 20910 USA. [Goldstein, Tracey] Univ Calif Davis, Sch Vet Med, Hlth Inst 1, Davis, CA 95616 USA. [Goodman, Simon J.] Univ Leeds, Sch Biol, Leeds LS2 9JT, W Yorkshire, England. [Grenfell, Bryan] NIH, Fogarty Int Ctr, Bethesda, MD 20892 USA. [Groch, Katia R.] Univ Sao Paulo, Sch Vet Med & Anim Sci, Dept Pathol, BR-05508270 Sao Paulo, Brazil. [Gulland, Frances] Marine Mammal Commiss, Bethesda, MD 20814 USA. [Hall, Ailsa] Univ St Andrews, Scottish Oceans Inst, Sea Mammal Res Unit, St Andrews KY16 8LB, Fife, Scotland. [Jensen, Brenda A.] Hawaii Pacific Univ, Dept Nat Sci, Kaneohe, HI 96744 USA. [Matassa, Keith] Pacific Marine Mammal Ctr, Laguna Beach, CA 92651 USA. [Mazzariol, Sandro] Univ Padua, Dept Comparat Biomed & Food Sci, I-35020 Legnaro Padua, Italy. [Nielsen, Ole] Dept Fisheries & Oceans Canada, Winnipeg, MB R3T 2N6, Canada. [Rotstein, David] Marine Mammal Pathol Serv, Olney, MD 20832 USA. [Saliki, Jeremy T.] Univ Georgia, Coll Vet Med, Athens Vet Diagnost Lab, Athens, GA 30602 USA. [Siebert, Ursula] Univ Vet Med, Inst Terr & Aquat Wildlife Res, D-30173 Hannover, Germany. [Waltzek, Thomas] Univ Florida, Coll Vet Med, Dept Infect Dis & Pathol, Gainesville, FL 32611 USA. [Wellehan, James F. X.] Univ Florida, Coll Vet Med, Dept Small Anim Clin Sci, Gainesville, FL 32610 USA. RP Duignan, PJ (reprint author), Univ Calgary, Dept Ecosyst & Publ Hlth, Calgary, AB T2N 4Z6, Canada. EM ppjduign@ucalgary.ca; mfb.cmed@gmail.com; Jason.Baker@noaa.gov; michelle.barbieri@noaa.gov; katie.colegrove@gmail.com; sylvain.deguise@uconn.edu; r.deswart@erasmusmc.nl; gdiguardo@unite.it; dobson@princeton.edu; pduprex@bu.edu; greg.early@yahoo.com; deborah.fauquier@noaa.gov; tgoldstein@ucdavis.edu; s.j.goodman@leeds.ac.uk; grenfell@princeton.edu; katia.groch@gmail.com; gullandf@tmmc.org; ajh7@st-andrews.ac.uk; bjensen@hpu.edu; klamy@gmail.com; kmatassa@pacificmmc.org; sandro.mazzariol@unipd.it; semorris@princeton.edu; ole.nielsen@dfo-mpo.gc.ca; drdrot@gmail.com; teri.rowles@noaa.gov; jsaliki@uga.edu; ursula.siebert@tiho-hannover.de; tomwaltzek@gmail.com; wellehanj@ufl.edu OI Mazzariol, Sandro/0000-0002-4756-1871; De Swart, Rik/0000-0003-3599-8969 FU RAPIDD program of the Science and Technology Directorate, Department of Homeland Security; Fogarty International Center, National Institutes of Health FX This review is the product of an international marine mammal morbillivirus workshop held at Princeton University, USA, in August 2014 and funded by the RAPIDD program of the Science and Technology Directorate, Department of Homeland Security and the Fogarty International Center, National Institutes of Health. NR 228 TC 7 Z9 7 U1 4 U2 50 PU MDPI AG PI BASEL PA POSTFACH, CH-4005 BASEL, SWITZERLAND SN 1999-4915 J9 VIRUSES-BASEL JI Viruses-Basel PD DEC PY 2014 VL 6 IS 12 BP 5093 EP 5134 DI 10.3390/v6125093 PG 42 WC Virology SC Virology GA AX3JA UT WOS:000346834500015 PM 25533658 ER PT J AU Van Bressem, MF Duignan, PJ Banyard, A Barbieri, M Colegrove, KM De Guise, S Di Guardo, G Dobson, A Domingo, M Fauquier, D Fernandez, A Goldstein, T Grenfell, B Groch, KR Gulland, F Jensen, BA Jepson, PD Hall, A Kuiken, T Mazzariol, S Morris, SE Nielsen, O Raga, JA Rowles, TK Saliki, J Sierra, E Stephens, N Stone, B Tomo, I Wang, J Waltzek, T Wellehan, JFX AF Van Bressem, Marie-Francoise Duignan, Padraig J. Banyard, Ashley Barbieri, Michelle Colegrove, Kathleen M. De Guise, Sylvain Di Guardo, Giovanni Dobson, Andrew Domingo, Mariano Fauquier, Deborah Fernandez, Antonio Goldstein, Tracey Grenfell, Bryan Groch, Katia R. Gulland, Frances Jensen, Brenda A. Jepson, Paul D. Hall, Ailsa Kuiken, Thijs Mazzariol, Sandro Morris, Sinead E. Nielsen, Ole Raga, Juan A. Rowles, Teresa K. Saliki, Jeremy Sierra, Eva Stephens, Nahiid Stone, Brett Tomo, Ikuko Wang, Jianning Waltzek, Thomas Wellehan, James F. X. TI Cetacean Morbillivirus: Current Knowledge and Future Directions SO VIRUSES-BASEL LA English DT Review DE cetacean morbillivirus; epidemics; mass stranding; SLAM; phylogeny; pathogenesis; diagnosis; endemic infections ID DOLPHINS STENELLA-COERULEOALBA; CANINE-DISTEMPER-VIRUS; BOTTLE-NOSED DOLPHINS; PORPOISES PHOCOENA-PHOCOENA; GULF-OF-MEXICO; SUBACUTE SCLEROSING-PANENCEPHALITIS; POLYMERASE-CHAIN-REACTION; PETITS RUMINANTS VIRUS; MEASLES-VIRUS; STRIPED DOLPHINS AB We review the molecular and epidemiological characteristics of cetacean morbillivirus (CeMV) and the diagnosis and pathogenesis of associated disease, with six different strains detected in cetaceans worldwide. CeMV has caused epidemics with high mortality in odontocetes in Europe, the USA and Australia. It represents a distinct species within the Morbillivirus genus. Although most CeMV strains are phylogenetically closely related, recent data indicate that morbilliviruses recovered from Indo-Pacific bottlenose dolphins (Tursiops aduncus), from Western Australia, and a Guiana dolphin (Sotalia guianensis), from Brazil, are divergent. The signaling lymphocyte activation molecule (SLAM) cell receptor for CeMV has been characterized in cetaceans. It shares higher amino acid identity with the ruminant SLAM than with the receptors of carnivores or humans, reflecting the evolutionary history of these mammalian taxa. In Delphinidae, three amino acid substitutions may result in a higher affinity for the virus. Infection is diagnosed by histology, immunohistochemistry, virus isolation, RT-PCR, and serology. Classical CeMV-associated lesions include bronchointerstitial pneumonia, encephalitis, syncytia, and lymphoid depletion associated with immunosuppression. Cetaceans that survive the acute disease may develop fatal secondary infections and chronic encephalitis. Endemically infected, gregarious odontocetes probably serve as reservoirs and vectors. Transmission likely occurs through the inhalation of aerosolized virus but mother to fetus transmission was also reported. C1 [Van Bressem, Marie-Francoise] Peruvian Ctr Cetacean Res CEPEC, Cetacean Conservat Med Grp CMED, Lima 20, Peru. [Duignan, Padraig J.] Univ Calgary, Dept Ecosyst & Publ Hlth, Calgary, AB T2N 4Z6, Canada. [Banyard, Ashley] APHA, Wildlife Zoonoses & Vector Borne Dis Res Grp, Weybridge KT15 3NB, Surrey, England. [Barbieri, Michelle; Gulland, Frances] Marine Mammal Ctr, Sausalito, CA 94965 USA. [Colegrove, Kathleen M.] Univ Illinois, Coll Vet Med, Zool Pathol Program, Maywood, IL 60153 USA. [De Guise, Sylvain] Univ Connecticut, Dept Pathobiol & Vet Sci, Storrs, CT 06269 USA. [De Guise, Sylvain] Univ Connecticut, Connecticut Sea Grant Coll Program, Storrs, CT 06269 USA. [Di Guardo, Giovanni] Univ Teramo, Fac Vet Med, I-64100 Teramo, Italy. [Dobson, Andrew; Grenfell, Bryan; Morris, Sinead E.] Princeton Univ, Dept Ecol & Evolutionary Biol, Princeton, NJ 08544 USA. [Domingo, Mariano] Autonomous Univ Barcelona, Ctr Recerca Sanitat Anim CReSA, E-08193 Barcelona, Spain. [Fauquier, Deborah; Rowles, Teresa K.] Natl Marine Fisheries Serv, Marine Mammal Hlth & Stranding Response Program, Silver Spring, MD 20910 USA. [Fernandez, Antonio; Sierra, Eva] Univ Las Palmas Gran Canaria, Sch Vet, Inst Anim Hlth, Dept Vet Pathol, Las Palmas Gran Canaria 35413, Spain. [Goldstein, Tracey] Univ Calif Davis, Sch Vet Med, Hlth Inst 1, Davis, CA 95616 USA. [Grenfell, Bryan] NIH, Fogarty Int Ctr, Bethesda, MD 20892 USA. [Groch, Katia R.] Univ Sao Paulo, Sch Vet Med & Anim Sci, Dept Pathol, BR-05508207 Sao Paulo, Brazil. [Groch, Katia R.] Humpback Whale Inst, BR-45900000 Caravelas, Bahia, Brazil. [Gulland, Frances] Marine Mammal Commiss, Bethesda, MD 20814 USA. [Jensen, Brenda A.] Hawaii Pacific Univ, Dept Nat Sci, Kaneohe, HI 96744 USA. [Jepson, Paul D.] Zool Soc London, Inst Zool, London NW1 4RY, England. [Hall, Ailsa] Univ St Andrews, Scottish Oceans Inst, Sea Mammal Res Unit, St Andrews KY16 8LB, Fife, Scotland. [Kuiken, Thijs] Erasmus MC, Dept Virosci, NL-3015 CN Rotterdam, Netherlands. [Mazzariol, Sandro] Univ Padua, Dept Comparat Biomed & Food Sci, I-35020 Padua, Italy. [Nielsen, Ole] Cent & Arctic Reg, Dept Fisheries & Oceans Canada, Winnipeg, MB R3T 2N6, Canada. [Raga, Juan A.] Univ Valencia, Cavanilles Inst Biodivers & Evolutionary Biol, Marine Zool Unit, Valencia 22085, Spain. [Saliki, Jeremy] Univ Georgia, Athens Vet Diagnost Lab, Coll Vet Med, Athens, GA 30602 USA. [Stephens, Nahiid] Murdoch Univ, Sch Vet & Life Sci, Perth, WA 6150, Australia. [Stone, Brett] QML Vetnost, Murarrie, Qld 4172, Australia. [Tomo, Ikuko] S Australian Museum, Adelaide, SA 5000, Australia. [Wang, Jianning] CSIRO, East Geelong, Vic 3220, Australia. [Waltzek, Thomas] Univ Florida, Dept Infect Dis & Pathol, Coll Vet Med, Gainesville, FL 32611 USA. [Wellehan, James F. X.] Univ Florida, Dept Small Anim Clin Sci, Coll Vet Med, Gainesville, FL 32611 USA. RP Van Bressem, MF (reprint author), Peruvian Ctr Cetacean Res CEPEC, Cetacean Conservat Med Grp CMED, Lima 20, Peru. EM mfb.cmed@gmail.com; ppjduign@ucalgary.ca; ashley.banyard@apha.gsi.gov.uk; michelle.barbieri@noaa.gov; katie.colegrove@gmail.com; sylvain.deguise@uconn.edu; gdiguardo@unite.it; dobson@princeton.edu; Mariano.Domingo@cresa.uab.cat; deborah.fauquier@noaa.gov; afernandez@dmor.ulpgc.es; tgoldstein@ucdavis.edu; grenfell@princeton.edu; katia.groch@gmail.com; gullandf@tmmc.org; bjensen@hpu.edu; paul.jepson@ioz.ac.uk; ajh7@st-andrews.ac.uk; t.kuiken@erasmusmc.n1; sandro.mazzariol@unipd.it; semorris@princeton.edu; ole.nielsen@dfo-mpo.gc.ca; raga@uv.es; teri.rowles@noaa.gov; jsaliki@uga.edu; esierra@becarios.ulpgc.es; n.stephens@murdoch.edu.au; brett.stone@qml.com.au; ikuko.tomo@samuseum.sa.gov.au; Jianning.Wang@csiro.au; tomwaltzek@gmail.com; wellehanj@ufl.edu RI Banyard, Ashley/C-7998-2011; APHA, Staff publications/E-6082-2010; Fernandez, Antonio/G-3448-2015; Sierra, Eva/H-9352-2015; OI Banyard, Ashley/0000-0002-1286-9825; Fernandez, Antonio/0000-0001-5281-0521; Sierra, Eva/0000-0003-3749-8845; Mazzariol, Sandro/0000-0002-4756-1871; Raga, Juan Antonio/0000-0003-2687-2539 FU RAPIDD program of the Science and Technology Directorate, Department of Homeland Security; Fogarty International Center, National Institutes of Health; Swan River Trust; Department of Parks and Wildlife FX We kindly thank Rik de Swart for inviting us to participate to this special issue, K Van Waerebeek and Jason Baker for their constructive comments on this manuscript, two anonymous reviewers for their useful comments and suggestions and Rob Deaville for the image of a harbor porpoise. This work emerged from a meeting funded by the RAPIDD program of the Science and Technology Directorate, Department of Homeland Security and the Fogarty International Center, National Institutes of Health. N. Stephens thanks the Swan River Trust and the Department of Parks and Wildlife for their support. NR 162 TC 26 Z9 27 U1 6 U2 45 PU MDPI AG PI BASEL PA POSTFACH, CH-4005 BASEL, SWITZERLAND SN 1999-4915 J9 VIRUSES-BASEL JI Viruses-Basel PD DEC PY 2014 VL 6 IS 12 BP 5145 EP 5181 DI 10.3390/v6125145 PG 37 WC Virology SC Virology GA AX3JA UT WOS:000346834500017 PM 25533660 ER PT J AU Conde-Agudelo, A Romero, R AF Conde-Agudelo, Agustin Romero, Roberto TI Prediction of preterm birth in twin gestations using biophysical and biochemical tests SO AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY LA English DT Review DE cervical length; fetal fibronectin; predictive value of tests; pregnancy; premature birth ID TUMOR-NECROSIS-FACTOR; AMNIOTIC-FLUID INTERLEUKIN-6; MONOCYTE CHEMOTACTIC PROTEIN-1; HUMAN CHORIONIC-GONADOTROPIN; ACTIVATING PEPTIDE-1 INTERLEUKIN-8; SONOGRAPHIC CERVICAL LENGTH; FETAL GROWTH RESTRICTION; BLOOD-CELL COUNT; MULTIPLE PREGNANCIES; MICROBIAL INVASION AB The objective of this study was to determine the performance of biophysical and biochemical tests for the prediction of preterm birth in both asymptomatic and symptomatic women with twin gestations. We identified a total of 19 tests proposed to predict preterm birth, mainly in asymptomatic women. In these women, a single measurement of cervical length with transvaginal ultrasound before 25 weeks of gestation appears to be a good test to predict preterm birth. Its clinical potential is enhanced by the evidence that vaginal progesterone administration in asymptomatic women with twin gestations and a short cervix reduces neonatal morbidity and mortality associated with spontaneous preterm delivery. Other tests proposed for the early identification of asymptomatic women at increased risk of preterm birth showed minimal to moderate predictive accuracy. None of the tests evaluated in this review meet the criteria to be considered clinically useful to predict preterm birth among patients with an episode of preterm labor. However, a negative cervicovaginal fetal fibronectin test could be useful in identifying women who are not at risk for delivering within the next week, which could avoid unnecessary hospitalization and treatment. This review underscores the need to develop accurate tests for predicting preterm birth in twin gestations. Moreover, the use of interventions in these patients based on test results should be associated with the improvement of perinatal outcomes. C1 [Conde-Agudelo, Agustin; Romero, Roberto] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Perinatol Res Branch, NIH, Dept Hlth & Human Serv, Bethesda, MD 20892 USA. [Conde-Agudelo, Agustin; Romero, Roberto] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Perinatol Res Branch, NIH, Dept Hlth & Human Serv, Detroit, MI USA. [Romero, Roberto] Univ Michigan, Dept Obstet & Gynecol, Ann Arbor, MI 48109 USA. [Romero, Roberto] Michigan State Univ, Dept Epidemiol & Biostat, E Lansing, MI 48824 USA. RP Romero, R (reprint author), Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Perinatol Res Branch, NIH, Dept Hlth & Human Serv, Bethesda, MD 20892 USA. EM romeror@mail.nih.gov FU Intramural Research Program of the Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Department of Health and Human Services 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, Department of Health and Human Services. NR 139 TC 13 Z9 13 U1 0 U2 12 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0002-9378 EI 1097-6868 J9 AM J OBSTET GYNECOL JI Am. J. Obstet. Gynecol. PD DEC PY 2014 VL 211 IS 6 BP 583 EP 595 DI 10.1016/j.ajog.2014.07.047 PG 13 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA AW9NW UT WOS:000346585300005 PM 25072736 ER PT J AU Parry, S Zhang, HP Biggio, J Bukowski, R Varner, M Xu, YJ Andrews, WW Saade, GR Esplin, MS Leite, R Ilekis, J Reddy, UM Sadovsky, Y Blair, IA AF Parry, Samuel Zhang, Heping Biggio, Joseph Bukowski, Radek Varner, Michael Xu, Yaji Andrews, William W. Saade, George R. Esplin, M. Sean Leite, Rita Ilekis, John Reddy, Uma M. Sadovsky, Yoel Blair, Ian A. CA Eunice Kennedy Shriver Natl Inst C Genomic Proteomic Network Preterm TI Maternal serum serpin B7 is associated with early spontaneous preterm birth SO AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY LA English DT Article DE preterm birth; proteomics; serine proteinase inhibitors ID SPECTROMETRY-BASED PROTEOMICS; TANDEM MASS-SPECTROMETRY; AMNIOTIC-FLUID; STATISTICAL-MODEL; IGA NEPHROPATHY; IDENTIFICATION; BIOMARKERS; EXPRESSION; PROTEINS; MEGSIN AB OBJECTIVE: We sought to identify serum biomarkers of early spontaneous preterm birth (SPTB) using semiquantitative proteomic analyses. STUDY DESIGN: This was a nested case-control study of pregnant women with previous SPTB. Maternal serum was collected at 19-24 and 28-32 weeks' gestation, and analyzed by liquid chromatography-multiple reaction monitoring/mass spectrometry. Targeted and shotgun proteomics identified 31 candidate proteins that were differentially expressed in pooled serum samples from spontaneous preterm (cases [< 34 weeks]) and term (controls) deliveries. Candidate protein expression was compared in individual serum samples between cases and controls matched by age and race groups, and clinical site. Protein expression was verified by Western blot in the placenta and fetal membranes from cases and controls. RESULTS: Serum samples were available for 35 cases and 35 controls at 19-24 weeks, and 16 cases and 16 controls at 28-32 weeks. One protein, serpin B7, yielded serum concentrations that differed between cases and controls. The mean concentration of serpin B7 at 28-32 weeks was 1.5-fold higher in women with subsequent preterm deliveries compared to controls; there was no difference at 19-24 weeks. Higher levels of serpin B7 at both gestational age windows were associated with a shorter interval to delivery, and higher levels of serpin B7 in samples from 28-32 weeks were associated with a lower gestational age at delivery. Western blotting identified serpin B7 protein in placenta, amnion, and chorion from cases and controls. CONCLUSION: Targeted and shotgun serum proteomics analyses associated 1 protein, serpin B7, with early SPTB. Our results require validation in other cohorts and analysis of the possible mechanistic role of serpin B7 in parturition. C1 [Parry, Samuel; Leite, Rita] Univ Penn, Sch Med, Dept Obstet & Gynecol, Philadelphia, PA 19104 USA. [Zhang, Heping; Xu, Yaji] Yale Univ, Sch Publ Hlth, Collaborat Ctr Stat Sci, New Haven, CT USA. [Biggio, Joseph; Andrews, William W.] Univ Alabama Birmingham, Sch Med, Dept Obstet & Gynecol, Birmingham, AL USA. [Bukowski, Radek; Saade, George R.] Univ Texas Med Branch, Dept Obstet & Gynecol, Div Maternal Fetal Med, Galveston, TX 77555 USA. [Varner, Michael; Esplin, M. Sean] Univ Utah, Sch Med, Dept Obstet & Gynecol, Salt Lake City, UT 84132 USA. [Ilekis, John; Reddy, Uma M.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Pregnancy & Perinatol Branch, Ctr Dev Biol & Perinatal Med, Bethesda, MD USA. [Sadovsky, Yoel] Univ Pittsburgh, Magee Womens Res Inst, Sch Med, Pittsburgh, PA USA. [Blair, Ian A.] Univ Penn, Sch Med, Ctr Canc Pharmacol, Philadelphia, PA 19104 USA. RP Parry, S (reprint author), Univ Penn, Sch Med, Dept Obstet & Gynecol, Philadelphia, PA 19104 USA. EM parry@mail.med.upenn.edu RI Xu, Yaji/M-4985-2015; Varner, Michael/K-9890-2013 OI Varner, Michael/0000-0001-9455-3973 FU National Institutes of Health; Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD); National Center for Advancing Translational Sciences FX The National Institutes of Health, the Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD), and the National Center for Advancing Translational Sciences provided grant support for the NICHD Genomics and Proteomics Network for Preterm Birth (GPN). While NICHD staff had input into the study design, conduct, analysis, and manuscript drafting, the comments and views of the authors do not necessarily represent the views of the NICHD. NR 31 TC 2 Z9 2 U1 0 U2 5 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0002-9378 EI 1097-6868 J9 AM J OBSTET GYNECOL JI Am. J. Obstet. Gynecol. PD DEC PY 2014 VL 211 IS 6 AR 678.e1 DI 10.1016/j.ajog.2014.06.035 PG 12 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA AW9NW UT WOS:000346585300031 PM 24954659 ER PT J AU Yao, JH Taveira-DaSilva, AM Jones, AM Julien-Williams, P Stylianou, M Moss, J AF Yao, Jianhua Taveira-DaSilva, Angelo M. Jones, Amanda M. Julien-Williams, Patricia Stylianou, Mario Moss, Joel TI Sustained Effects of Sirolimus on Lung Function and Cystic Lung Lesions in Lymphangioleiomyomatosis SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Article DE sirolimus; lung cystic destruction; LAM ID TUBEROUS SCLEROSIS COMPLEX; PLACEBO-CONTROLLED TRIAL; GIANT-CELL ASTROCYTOMAS; PULMONARY LYMPHANGIOLEIOMYOMATOSIS; MATRIX METALLOPROTEINASES; TISSUE INHIBITORS; DOXYCYCLINE USE; GENE-PRODUCTS; TSC2; ACTIVATION AB Rationale: Sirolimus therapy stabilizes lung function and reduces the size of chylous effusions and lymphangioleiomyomas in patients with lymphangioleiomyomatosis. Objectives: to determine whether sirolimus has beneficial effects on lung function, cystic areas, and adjacent lung parenchyma; whether these effects are sustained; and whether sirolimus is well tolerated by patients. Methods: Lung function decline over time, lung volume occupied by cysts (cyst score), and lung tissue texture in the vicinity of the cysts were quantified with a computer-aided diagnosis system in 38 patients. Then we compared cyst scores from the last study on sirolimus with studies done on sirolimus therapy. In 12 patients, we evaluated rates of change in lung function and cyst scores off and on sirolimus. Measurements and Main Results: Sirolimus reduced yearly declines in FEV1 (-2.3 +/- 0.1 vs. 1.0 +/- 0.3% predicted; P < 0.001) and diffusing capacity of carbon monoxide (-2.6 +/- 0.1 vs. 0.9 +/- 0.2% predicted; P < 0.001). Cyst scores 1.2 +/- 0.8 years (30.5 +/- 11.9%) and 2.5 +/- 2 years (29.7 +/- 12.1%) after initiating sirolimus were not significantly different from pretreatment values (28.4 +/- 12.5%). In 12 patients followed for 5 years, a significant reduction in rates of yearly decline in FEV1 (-1.4 +/- 0.2 vs. 0.3 +/- 0.4% predicted; P = 0.025) was observed. Analyses of 104 computed tomography scans showed a nonsignificant (P = 0.23) reduction in yearly rates of change of cyst scores (1.8 +/- 0.2 vs. 0.3 +/- 0.3%; P = 0.23) and lung texture features. Despite adverse events, most patients were able to continue sirolimus therapy. Conclusions: Sirolimus therapy slowed down lung function decline and increase in cystic lesions. Most patients were able to tolerate sirolimus therapy. C1 [Yao, Jianhua] NHLBI, Radiol & Imaging Sci Dept, NIH, Bethesda, MD 20892 USA. [Taveira-DaSilva, Angelo M.; Jones, Amanda M.; Julien-Williams, Patricia; Moss, Joel] NHLBI, Cardiovasc & Pulm Branch, NIH, Bethesda, MD 20892 USA. [Stylianou, Mario] NHLBI, Off Biostat Res, NIH, Bethesda, MD 20892 USA. RP Taveira-DaSilva, AM (reprint author), NHLBI, Cardiovasc & Pulm Branch, NIH, Bldg 10,Room 6D03,MSC 1590, Bethesda, MD 20892 USA. EM dasilvaa@nhlbi.nih.gov FU Intramural Research Program, National Institutes of Health, NHLBI [95-H-0186] FX Supported by the Intramural Research Program, National Institutes of Health, NHLBI (Protocol 95-H-0186, J.M.). NR 47 TC 16 Z9 16 U1 0 U2 2 PU AMER THORACIC SOC PI NEW YORK PA 25 BROADWAY, 18 FL, NEW YORK, NY 10004 USA SN 1073-449X EI 1535-4970 J9 AM J RESP CRIT CARE JI Am. J. Respir. Crit. Care Med. PD DEC 1 PY 2014 VL 190 IS 11 BP 1273 EP 1282 DI 10.1164/rccm.201405-09180C PG 10 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA AW5RF UT WOS:000346331000011 PM 25329516 ER PT J AU Duncan, K Sturke, R AF Duncan, Kalina Sturke, Rachel TI NIH TOBACCO OR HEALTH RESEARCH AND CAPACITY BUILDING GRANT PROGRAM REVIEW SO ASIA-PACIFIC JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract C1 [Duncan, Kalina] NCI, Rockville, MD USA. [Sturke, Rachel] Fogarty Int Ctr, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1743-7555 EI 1743-7563 J9 ASIA-PAC J CLIN ONCO JI Asia-Pac. J. Clin. Oncol. PD DEC PY 2014 VL 10 SU 9 SI SI MA 304 BP 1 EP 2 PG 2 WC Oncology SC Oncology GA AW5XG UT WOS:000346343700005 ER PT J AU Vinson, C Stevens, L Torode, J Saraiya, M Sutcliffe, S Gospodacrowicz, M Anderson, B Adewole, I Luciani, S AF Vinson, Cynthia Stevens, Lisa Torode, Julie Saraiya, Mona Sutcliffe, Simon Gospodacrowicz, Mary Anderson, Benjamin Adewole, Isaac Luciani, Silvana TI AN INTERNATIONAL PARTNERSHIP TO ALIGN CANCER CONTROL PLANNING EFFORTS WITH GLOBAL NONCOMMUNICABLE DISEASE (NCD) CONTROL TARGETS SO ASIA-PACIFIC JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract C1 [Vinson, Cynthia; Stevens, Lisa] NCI, Bethesda, MD 20892 USA. [Torode, Julie] UICC, Geneva, Switzerland. [Saraiya, Mona] Ctr Dis Control & Prevent, Atlanta, GA USA. [Sutcliffe, Simon] Int Canc Control Congress Assoc, Vancouver, BC, Canada. [Gospodacrowicz, Mary] Univ Toronto, Princess Margaret Hosp, Toronto, ON, Canada. [Anderson, Benjamin] Fred Hutchinson Canc Res Ctr, Seattle, WA 98104 USA. [Adewole, Isaac] African Org Res & Training Canc, Ibadan, Nigeria. [Luciani, Silvana] Pan Amer Hlth Org, Washington, DC USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1743-7555 EI 1743-7563 J9 ASIA-PAC J CLIN ONCO JI Asia-Pac. J. Clin. Oncol. PD DEC PY 2014 VL 10 SU 9 SI SI MA 326 BP 8 EP 8 PG 1 WC Oncology SC Oncology GA AW5XG UT WOS:000346343700022 ER PT J AU Galassi, A Burg, A Schneider, J Williams, M Al-Ruzzieh, M Bigirimana, JB Buswell, L Challinor, J Cummings, G Day, S de Calvo, LEA Houlihan, K Nevidjon, B Teahon, M So, WN Were, P AF Galassi, Annette Burg, Allison Schneider, Julie Williams, Makeda Al-Ruzzieh, Majeda Bigirimana, Jean Bosco Buswell, Lori Challinor, Julia Cummings, Greta Day, Sara Esperanza Ayala de Calvo, Luz Houlihan, Kathy Nevidjon, Brenda Teahon, Marina So, Winnie Were, Pamela TI BUILDING CAPACITY FOR ONCOLOGY NURSING EDUCATION AND TRAINING IN LOW- AND MIDDLE-INCOME COUNTRIES: A CALL TO ACTION SO ASIA-PACIFIC JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract C1 [Galassi, Annette; Schneider, Julie; Williams, Makeda] NCI, Rockville, MD USA. [Burg, Allison] Amer Soc Clin Oncol, Alexandria, VA USA. [Al-Ruzzieh, Majeda] King Hussein Canc Ctr, Amman, Jordan. [Bigirimana, Jean Bosco] Inshuti Mu Buzima, Rwinkwavu, Rwanda. [Buswell, Lori; Houlihan, Kathy] Dana Farber Canc Inst, Boston, MA 02115 USA. [Challinor, Julia] Int Network Canc Treatment & Res, Brussels, Belgium. [Cummings, Greta; Nevidjon, Brenda] Int Soc Nurses Canc Care, Vancouver, BC, Canada. [Day, Sara] St Jude Childrens Res Hosp, Memphis, TN 38105 USA. [Teahon, Marina] Union Int Canc Control, Geneva, Switzerland. [So, Winnie] Chinese Univ Hong Kong, Shatin, Hong Kong, Peoples R China. [Were, Pamela] Epidemiol Burkitt Lymphoma East African Children, Eldoret, Kenya. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1743-7555 EI 1743-7563 J9 ASIA-PAC J CLIN ONCO JI Asia-Pac. J. Clin. Oncol. PD DEC PY 2014 VL 10 SU 9 SI SI MA 330 BP 9 EP 9 PG 1 WC Oncology SC Oncology GA AW5XG UT WOS:000346343700026 ER PT J AU Cremer, M Maza, M Alfaro, K Gage, J Castle, P Kim, J AF Cremer, Miriam Maza, Mauricio Alfaro, Karla Gage, Julia Castle, Philip Kim, Jane TI INTRODUCING CAREHPV INTO A PUBLIC SECTOR SCREENING PROGRAM IN EL SALVADOR SO ASIA-PACIFIC JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract C1 [Cremer, Miriam] Univ Pittsburgh, Med Ctr, Pittsburgh, PA USA. [Maza, Mauricio; Alfaro, Karla] Basic Hlth Int, San Salvador, El Salvador. [Gage, Julia] NCI, Bethesda, MD 20892 USA. [Kim, Jane] Harvard Univ, Sch Publ Hlth, Cambridge, MA 02138 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1743-7555 EI 1743-7563 J9 ASIA-PAC J CLIN ONCO JI Asia-Pac. J. Clin. Oncol. PD DEC PY 2014 VL 10 SU 9 SI SI MA 341 BP 13 EP 13 PG 1 WC Oncology SC Oncology GA AW5XG UT WOS:000346343700036 ER PT J AU Sun, L Dickie, L Adamo, P Li, J Houston, K Su, J AF Sun, Leon Dickie, Lois Adamo, Peggy Li, Jun Houston, Keisha Su, Joseph TI EPIDEMIOLOGICAL AND CLINICAL CHARACTERISTICS OF PROSTATE CANCER MEN WITH MULTIPLE CANCERS SO ASIA-PACIFIC JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract C1 [Sun, Leon; Dickie, Lois; Adamo, Peggy] NCI, NIH, Rockville, MD USA. [Li, Jun] Ctr Dis Control & Prevent, Div Canc Prevent & Control, Atlanta, GA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1743-7555 EI 1743-7563 J9 ASIA-PAC J CLIN ONCO JI Asia-Pac. J. Clin. Oncol. PD DEC PY 2014 VL 10 SU 9 SI SI MA 539 BP 56 EP 57 PG 2 WC Oncology SC Oncology GA AW5XG UT WOS:000346343700163 ER PT J AU Duncan, K Galassi, A Williams, M AF Duncan, Kalina Galassi, Annette Williams, Makeda TI JOINING FORCES TO OVERCOME CANCER: THE KENYA CANCER RESEARCH AND CONTROL STAKEHOLDER MEETING EXPERIENCE SO ASIA-PACIFIC JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract C1 [Duncan, Kalina; Galassi, Annette; Williams, Makeda] NCI, Rockville, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1743-7555 EI 1743-7563 J9 ASIA-PAC J CLIN ONCO JI Asia-Pac. J. Clin. Oncol. PD DEC PY 2014 VL 10 SU 9 SI SI MA 696 BP 104 EP 104 PG 1 WC Oncology SC Oncology GA AW5XG UT WOS:000346343700310 ER PT J AU Khrushchinskii, AA Kuten', SA Minenko, VF Zhukova, OM Podgaiskaya, AA Germenchuk, MG Kukhta, TA Vakulovskii, SM Drozdovitch, VV AF Khrushchinskii, A. A. Kuten', S. A. Minenko, V. F. Zhukova, O. M. Podgaiskaya, A. A. Germenchuk, M. G. Kukhta, T. A. Vakulovskii, S. M. Drozdovitch, V. V. TI Radionuclide Ratios in Precipitation on the Territory of Belarus After the Chernobyl Accident: Calculation from Gamma-Spectrometric Measurements on Soil in May-July 1986 SO ATOMIC ENERGY LA English DT Article AB The correlations between the fallout density and ratio of radionuclides in different regions of Belarus after the accident at the Chernobyl NPP are investigated using data obtained by means of gamma-spectrometric measurements performed on soil in May-July 1986. It is shown that the isotopes of cesium and/or ruthenium are most suitable for reconstructing the activity of I-131 in the fallout. Charts showing the isolines of the activity ratios I-131/Cs-137 and Cs-134/Cs-137 in the fallout are constructed. The geometric averages obtained for the log-normal distribution of the ratios Cs-134/Cs-137 and I-131/Cs-137 in terms of May 10, 1986 equal 0.47 and 5.4, respectively. The distribution of the activity ratio I-131/Cs-137 in the fallout and the correlation coefficients show that on the whole there is no consistent interrelation between the fallout indices of these radionuclides over the territory. C1 [Khrushchinskii, A. A.; Kuten', S. A.; Minenko, V. F.] Belarusian State Univ, Res Inst Nucl Problems, Minsk 220050, Byelarus. [Zhukova, O. M.; Podgaiskaya, A. A.; Germenchuk, M. G.] Minist Nat Resources Republ Belarus, Republican Ctr Radiat Control & Environm Monitori, Minsk, Byelarus. [Kukhta, T. A.] Joint Inst Informat Problems, Minsk, Byelarus. [Vakulovskii, S. M.] Taifun Sci Ind Assoc, Obninsk, Russia. [Drozdovitch, V. V.] NCI, Bethesda, MD 20892 USA. RP Khrushchinskii, AA (reprint author), Belarusian State Univ, Res Inst Nucl Problems, Minsk 220050, Byelarus. RI Kuten, Semen/F-6699-2016 OI Kuten, Semen/0000-0003-0827-8421 FU International Scientific and Technical Center [MNTTs-B-488P, MNTTS-3452]; National Cancer Institute (USA) FX This work was performed as part of the projects MNTTs-B-488P and MNTTS-3452 of the International Scientific and Technical Center with the financial support from the National Cancer Institute (USA). NR 16 TC 1 Z9 1 U1 2 U2 4 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1063-4258 EI 1573-8205 J9 ATOM ENERGY+ JI Atom. Energy PD DEC PY 2014 VL 117 IS 2 BP 143 EP 148 DI 10.1007/s10512-014-9902-4 PG 6 WC Nuclear Science & Technology SC Nuclear Science & Technology GA AW4FF UT WOS:000346235800011 ER PT J AU Buchanan, S Noinaj, N Kuszak, AJ Gumbart, JC Lukacik, P Chang, H Easley, NC Lithgow, T AF Buchanan, S. Noinaj, N. Kuszak, A. J. Gumbart, J. C. Lukacik, P. Chang, H. Easley, N. C. Lithgow, T. TI Structural insight into the biogenesis of beta-barrel membrane proteins SO BIOCHEMISTRY AND CELL BIOLOGY-BIOCHIMIE ET BIOLOGIE CELLULAIRE LA English DT Meeting Abstract C1 [Buchanan, S.; Noinaj, N.; Kuszak, A. J.; Chang, H.; Easley, N. C.] NIDDK, NIH, Bethesda, MD 20892 USA. [Gumbart, J. C.] Georgia Inst Technol, Atlanta, GA 30332 USA. [Lukacik, P.] Harwell Sci & Innovat Campus, Diamond Light Source, Didcot OX11 0QX, Oxon, England. [Lithgow, T.] Monash Univ, Clayton, Vic 3800, Australia. NR 0 TC 0 Z9 0 U1 0 U2 4 PU CANADIAN SCIENCE PUBLISHING, NRC RESEARCH PRESS PI OTTAWA PA 65 AURIGA DR, SUITE 203, OTTAWA, ON K2E 7W6, CANADA SN 0829-8211 EI 1208-6002 J9 BIOCHEM CELL BIOL JI Biochem. Cell Biol. PD DEC PY 2014 VL 92 IS 6 BP 597 EP 597 PG 1 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA AW6FX UT WOS:000346366200101 ER PT J AU Wentzensen, N Fetterman, B Tokugawa, D Schiffman, M Castle, PE Wood, SN Stiemerling, E Poitras, N Lorey, T Kinney, W AF Wentzensen, Nicolas Fetterman, Barbara Tokugawa, Diane Schiffman, Mark Castle, Philip E. Wood, Shannon N. Stiemerling, Eric Poitras, Nancy Lorey, Thomas Kinney, Walter TI Interobserver Reproducibility and Accuracy of p16/Ki-67 Dual-Stain Cytology in Cervical Cancer Screening SO CANCER CYTOPATHOLOGY LA English DT Article DE cervical cancer screening; p16; Ki-67; human papillomavirus; reproducibility; cytology; Papanicolaou test ID HPV-POSITIVE WOMEN; INTRAEPITHELIAL NEOPLASIA; HUMAN-PAPILLOMAVIRUS; TRIAGE; POPULATION; COLPOSCOPY; PRECURSORS; CELLS; ASCUS; RISK AB BACKGROUNDDual-stain cytology for p16 and Ki-67 has been proposed as a biomarker in cervical cancer screening. The authors evaluated the reproducibility and accuracy of dual-stain cytology among 10 newly trained evaluators. METHODSIn total, 480 p16/Ki-67-stained slides from human papillomavirus-positive women were evaluated in masked fashion by 10 evaluators. None of the evaluators had previous experience with p16 or p16/Ki-67 cytology. All participants underwent p16/Ki-67 training and subsequent proficiency testing. Reproducibility of dual-stain cytology was measured using the percentage agreement, individual and aggregate values, as well as McNemar statistics. Clinical performance for the detection of cervical intraepithelial neoplasia grade 2 or greater (CIN2+) was evaluated for each individual evaluator and for all evaluators combined compared with the reference evaluation by a cytotechnologist who had extensive experience with dual-stain cytology. RESULTSThe percentage agreement of individual evaluators with the reference evaluation ranged from 83% to 91%, and the values ranged from 0.65 to 0.81. The combined value was 0.71 for all evaluators and 0.73 for cytotechnologists. The average sensitivity and specificity for the detection of CIN2+ among novice evaluators was 82% and 64%, respectively; whereas the reference evaluation had 84% sensitivity and 63% specificity, respectively. Agreement on dual-stain positivity increased with greater numbers of p16/Ki-67-positive cells on the slides. CONCLUSIONSGood to excellent reproducibility of p16/Ki-67 dual-stain cytology was observed with almost identical clinical performance of novice evaluators compared with reference evaluations. The current findings suggest that p16/Ki-67 dual-stain evaluation can be implemented in routine cytology practice with limited training. Cancer (Cancer Cytopathol) 2014;122:914-920. (c) 2014 American Cancer Society. The authors evaluate the reproducibility and accuracy of p16/Ki-67 dual-stain cytology among 10 newly trained evaluators. The results indicate that the evaluation of p16/Ki-67 dual staining on cytology slides can be implemented in routine cytology practice with limited training and good to excellent reproducibility. C1 [Wentzensen, Nicolas; Schiffman, Mark; Wood, Shannon N.] NCI, Div Canc Epidemiol & Genet, NIH, Rockville, MD USA. [Fetterman, Barbara; Tokugawa, Diane; Stiemerling, Eric; Poitras, Nancy; Lorey, Thomas] Kaiser Permanente, Permanente Med Grp Reg Lab, Berkeley, CA USA. [Castle, Philip E.] Global Coalit Cerv Canc, Arlington, VA USA. [Kinney, Walter] Kaiser Permanente Med Care Program, Div Gynecol Oncol, Oakland, CA USA. RP Wentzensen, N (reprint author), NCI, Div Canc Epidemiol & Genet, 9609 Med Ctr Dr,Room 7-E114, Bethesda, MD 20892 USA. EM wentzenn@mail.nih.gov FU Roche; BD; GE Healthcare; Cepheid; Hologic; Qiagen; ClearPath; Guided Therapeutics FX Dr. Wentzensen reports non-financial support from mtm Laboratories. Dr. Schiffman reports that Roche has performed HPV tests at no cost for NCI-sponsored studies; the results are published collaboratively. Dr. Castle is compensated for serving on a Merck Data and Safety Monitoring Board for HPV vaccines and has served as a paid consultant to Roche, BD, GE Healthcare, Cepheid, and Hologic; he reports personal fees from Qiagen, BD, ClearPath, Guided Therapeutics, Cepheid, and GE Healthcare and non-financial support from Roche, Qiagen, Norchip, and mtm Laboratories. NR 16 TC 14 Z9 15 U1 0 U2 2 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1934-662X EI 1934-6638 J9 CANCER CYTOPATHOL JI Cancer Cytopathol. PD DEC PY 2014 VL 122 IS 12 BP 914 EP 920 DI 10.1002/cncy.21473 PG 7 WC Oncology; Pathology SC Oncology; Pathology GA AW5YY UT WOS:000346348000011 PM 25132656 ER PT J AU Soto-Pantoja, DR Terabe, M Ghosh, A Ridnour, LA DeGraff, WG Wink, DA Berzofsky, JA Roberts, DD AF Soto-Pantoja, David R. Terabe, Masaki Ghosh, Arunima Ridnour, Lisa A. DeGraff, William G. Wink, David A. Berzofsky, Jay A. Roberts, David D. TI CD47 in the Tumor Microenvironment Limits Cooperation between Antitumor T-cell Immunity and Radiotherapy SO CANCER RESEARCH LA English DT Article ID DENDRITIC CELLS; STEM-CELLS; THROMBOSPONDIN-1; ANTIBODY; PROTEIN; CANCER; PHAGOCYTOSIS; INTEGRIN; MODEL; IMMUNOSURVEILLANCE AB Although significant advances in radiotherapy have increased its effectiveness in many cancer settings, general strategies to widen the therapeutic window between normal tissue toxicity and malignant tumor destruction would still offer great value. CD47 blockade has been found to confer radioprotection to normal tissues while enhancing tumor radiosensitivity. Here, we report that CD47 blockade directly enhances tumor immunosurveillance by CD8(+) T cells. Combining CD47 blockade with irradiation did not affect fibrosarcoma growth in T cell-deficient mice, whereas adoptive transfer of tumor-specific CD8(+) T cells restored combinatorial efficacy. Furthermore, ablation of CD8(+) T cells abolished radiotherapeutic response in immunocompetent syngeneic hosts. CD47 blockade in either target cells or effector cells was sufficient to enhance antigen-dependent CD8(+) CTL-mediated tumor cell killing in vitro. In CD47-deficient syngeneic hosts, engrafted B16 melanomas were 50% more sensitive to irradiation, establishing that CD47 expression in the microenvironment was sufficient to limit tumor radiosensitivity. Mechanistic investigations revealed increased tumor infiltration by cytotoxic CD8(+) T cells in a CD47-deficient microenvironment, with an associated increase in T cell-dependent intratumoral expression of granzyme B. Correspondingly, an inverse correlation between CD8(+) T-cell infiltration and CD47 expression was observed in human melanomas. Our findings establish that blocking CD47 in the context of radiotherapy enhances antitumor immunity by directly stimulating CD8(+) cytotoxic T cells, with the potential to increase curative responses. (C) 2014 AACR. C1 [Soto-Pantoja, David R.; Ghosh, Arunima; Roberts, David D.] NCI, Pathol Lab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. [Terabe, Masaki; Berzofsky, Jay A.] NCI, Vaccine Branch, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. [Ridnour, Lisa A.; DeGraff, William G.; Wink, David A.] NCI, Radiat Biol Branch, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. RP Roberts, DD (reprint author), NCI, Pathol Lab, Ctr Canc Res, NIH, 10 Ctr Dr, Bethesda, MD 20892 USA. EM dr9y@nih.gov RI Roberts, David/A-9699-2008 OI Roberts, David/0000-0002-2481-2981 FU Intramural Research Program of the NIH/NCI FX This work was supported by the Intramural Research Program of the NIH/NCI (D.D. Roberts, D.A. Wink, and J.A. Berzofsky). NR 55 TC 26 Z9 26 U1 2 U2 18 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD DEC 1 PY 2014 VL 74 IS 23 BP 6771 EP 6783 DI 10.1158/0008-5472.AN-14-0037-T PG 13 WC Oncology SC Oncology GA AW6EN UT WOS:000346362400005 PM 25297630 ER PT J AU Lapeire, L Hendrix, A Lambein, K Van Bockstal, M Braems, G Van Den Broecke, R Limame, R Mestdagh, P Vandesompele, J Vanhove, C Maynard, D Lehuede, C Muller, C Valet, P Gespach, CP Bracke, M Cocquyt, V Denys, H De Wever, O AF Lapeire, Lore Hendrix, An Lambein, Kathleen Van Bockstal, Mieke Braems, Geert Van Den Broecke, Rudy Limame, Ridha Mestdagh, Pieter Vandesompele, Jo Vanhove, Christian Maynard, Dawn Lehuede, Camille Muller, Catherine Valet, Philippe Gespach, Christian P. Bracke, Marc Cocquyt, Veronique Denys, Hannelore De Wever, Olivier TI Cancer-Associated Adipose Tissue Promotes Breast Cancer Progression by Paracrine Oncostatin M and Jak/STAT3 Signaling SO CANCER RESEARCH LA English DT Article ID EPITHELIAL-CELLS; GENE-EXPRESSION; RHEUMATOID-ARTHRITIS; TUMOR PROGRESSION; STROMAL CELLS; STEM-CELLS; IN-VIVO; DIFFERENTIATION; INVASION; TUMORIGENESIS AB Increasing evidence supports the critical roles played by adipose tissue in breast cancer progression. Yet, the mediators and mechanisms are poorly understood. Here, we show that breast cancer-associated adipose tissue from freshly isolated tumors promotes F-actin remodeling, cellular scattering, invasiveness, and spheroid reorganization of cultured breast cancer cells. A combination of techniques, including transcriptomics, proteomics, and kinomics enabled us to identify paracrine secretion of oncostatin M (OSM) by cancer-associated adipose tissue. Specifically, OSM, expressed by CD45(+) leucocytes in the stromal vascular fraction, induced phosphorylation of STAT3 (pSTAT3-) Y705 and S727 in breast cancer cells and transcription of several STAT3-dependent genes, including S100 family members S100A7, S100A8, and S100A9. Autocrine activation of STAT3 in MCF-7 cells ectopically expressing OSM-induced cellular scattering and peritumoral neovascularization of orthotopic xenografts. Conversely, selective inhibition of OSM by neutralizing antibody and Jak family kinases by tofacitinib inhibited STAT3 signaling, peritumoral angiogenesis, and cellular scattering. Importantly, nuclear staining of pSTAT3-Y705 identified at the tumor invasion front in ductal breast carcinomas correlates with increased lymphovascular invasion. Our work reveals the potential of novel therapeutic strategies targeting the OSM and STAT3 axis in patients with breast cancer harboring nuclear pSTAT3-Y705. (C) 2014 AACR. C1 [Lapeire, Lore; Cocquyt, Veronique; Denys, Hannelore] Ghent Univ Hosp, Dept Med Oncol, B-9000 Ghent, Belgium. [Hendrix, An; Bracke, Marc; De Wever, Olivier] Ghent Univ Hosp, Dept Radiat Oncol & Expt Canc Res, Lab Expt Canc Res, B-9000 Ghent, Belgium. [Lambein, Kathleen; Van Bockstal, Mieke] Ghent Univ Hosp, Dept Pathol, B-9000 Ghent, Belgium. [Braems, Geert; Van Den Broecke, Rudy] Ghent Univ Hosp, Dept Gynaecol, B-9000 Ghent, Belgium. [Limame, Ridha] Univ Antwerp, Ctr Oncol Res CORE, B-2020 Antwerp, Belgium. [Mestdagh, Pieter; Vandesompele, Jo] Ghent Univ Hosp, Ctr Med Genet, B-9000 Ghent, Belgium. [Vanhove, Christian] Ghent Univ Hosp, Inst Biomed Technol, B-9000 Ghent, Belgium. [Maynard, Dawn] NHGRI, Med Genet Branch, Bethesda, MD 20892 USA. [Lehuede, Camille; Muller, Catherine] Univ Toulouse, UPS, Inst Pharmacol & Biol Struct, Toulouse, France. [Valet, Philippe] Univ Toulouse 3, INSERM, U1048, F-31062 Toulouse, France. [Gespach, Christian P.] Univ Paris 06, INSERM, U938, Paris, France. RP De Wever, O (reprint author), Ghent Univ Hosp, Dept Radiat Oncol & Expt Canc Res, Lab Expt Canc Res, De Pintelaan 185, B-9000 Ghent, Belgium. EM olivier.dewever@ugent.be RI de wever, olivier/J-3094-2013; MULLER, Catherine/E-2060-2011 OI de wever, olivier/0000-0002-5453-760X; FU Fund for Scientific Spearheads of Ghent University Hospital and Research Council of Ghent University; National Cancer Plan [KPC_ 29_ 012]; "Bijzonder Onderzoeksfonds" (BOF) of Ghent University; Fund for Scientific Research-Flanders FX This research was supported by Fund for Scientific Spearheads of Ghent University Hospital and Research Council of Ghent University, the National Cancer Plan (KPC_ 29_ 012), a grant from the "Bijzonder Onderzoeksfonds" (BOF) of Ghent University (to H. Denys), a postdoctoral grant (to A. Hendrix), and a travel grant (L. Lapeire) from Fund for Scientific Research-Flanders. NR 53 TC 17 Z9 17 U1 1 U2 10 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD DEC 1 PY 2014 VL 74 IS 23 BP 6806 EP 6819 DI 10.1158/0008-5472.CAN-14-0160 PG 14 WC Oncology SC Oncology GA AW6EN UT WOS:000346362400008 PM 25252914 ER PT J AU Josse, R Martin, SE Guha, R Ormanoglu, P Pfister, TD Reaper, PM Barnes, CS Jones, J Charlton, P Pollard, JR Morris, J Doroshow, JH Pommier, Y AF Josse, Rozenn Martin, Scott E. Guha, Rajarshi Ormanoglu, Pinar Pfister, Thomas D. Reaper, Philip M. Barnes, Christopher S. Jones, Julie Charlton, Peter Pollard, John R. Morris, Joel Doroshow, James H. Pommier, Yves TI ATR Inhibitors VE-821 and VX-970 Sensitize Cancer Cells to Topoisomerase I Inhibitors by Disabling DNA Replication Initiation and Fork Elongation Responses SO CANCER RESEARCH LA English DT Article ID S-PHASE CHECKPOINT; MULTIDRUG-RESISTANCE; DAMAGE RESPONSE; PROTEIN-KINASE; SINGLE-CELL; ACTIVATION; CAMPTOTHECIN; ANTICANCER; RADIATION; STRESS AB Camptothecin and its derivatives, topotecan and irinotecan, are specific topoisomerase I (Top1) inhibitors and potent anticancer drugs killing cancer cells by producing replication-associated DNA double-strand breaks, and the indenoisoquinoline LMP-400 (indotecan) is a novel Top1 inhibitor in clinical trial. To develop novel drug combinations, we conducted a synthetic lethal siRNA screen using a library that targets nearly 7,000 human genes. Depletion of ATR, the main transducer of replication stress, came as a top candidate gene for camptothecin synthetic lethality. Validation studies using ATR siRNA and the ATR inhibitor VE-821 confirmed marked antiproliferative synergy with camptothecin and even greater synergy with LMP-400. Single-cell analyses and DNA fiber combing assays showed that VE-821 abrogates the S-phase replication elongation checkpoint and the replication origin-firing checkpoint induced by camptothecin and LMP-400. As expected, the combination of Top1 inhibitors with VE-821 inhibited the phosphorylation of ATR and Chk1; however, it strongly induced gamma H2AX. In cells treated with the combination, the gamma H2AX pattern changed over time from the well-defined Top1-induced damage foci to an intense peripheral and diffuse nuclear staining, which could be used as response biomarker. Finally, the clinical derivative of VE-821, VX-970, enhanced the in vivo tumor response to irinotecan without additional toxicity. A key implication of our work is the mechanistic rationale and proof of principle it provides to evaluate the combination of Top1 inhibitors with ATR inhibitors in clinical trials. (C) 2014 AACR. C1 [Josse, Rozenn; Doroshow, James H.; Pommier, Yves] NCI, Dev Therapeut Branch, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. [Josse, Rozenn; Doroshow, James H.; Pommier, Yves] NCI, Mol Pharmacol Lab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. [Martin, Scott E.; Guha, Rajarshi; Ormanoglu, Pinar] NIH, Natl Ctr Adv Translat Sci, Div Preclin Innovat, Rockville, MD USA. [Pfister, Thomas D.] Leidos Biomed Res Inc, Natl Lab Canc Res, Lab Human Toxicol & Pharmacol, Appl Dev Res Directorate, Frederick, MD USA. [Reaper, Philip M.; Barnes, Christopher S.; Jones, Julie; Charlton, Peter; Pollard, John R.] Vertex Pharmaceut Europe Ltd, Abingdon, Oxon, England. [Morris, Joel; Doroshow, James H.] NCI, Drug Synth & Chem Branch, Div Canc Treatment, Div Canc Treatment & Diag DTP DCTD,NIH, Bethesda, MD 20892 USA. RP Pommier, Y (reprint author), NCI, NIH, 37 Convent Dr,Bldg 37,Room 5068, Bethesda, MD 20892 USA. EM pommier@nih.gov FU NCI Intramural Program, Center for Cancer Research [Z01-BC006161, Z01-BC006150]; Federal funds from NCI, NIH [HHSN261200800001E]; American Recovery and Reinvestment Act funds FX The studies were supported by the NCI Intramural Program, Center for Cancer Research (Z01-BC006161 and Z01-BC006150), by the Federal funds from the NCI, NIH under contract no. HHSN261200800001E, and in part by the American Recovery and Reinvestment Act funds. NR 50 TC 25 Z9 27 U1 2 U2 18 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD DEC 1 PY 2014 VL 74 IS 23 BP 6968 EP 6979 DI 10.1158/0008-5472.CAN-13-3369 PG 12 WC Oncology SC Oncology GA AW6EN UT WOS:000346362400022 PM 25269479 ER PT J AU Gordon, MS Robert, F Matei, D Mendelson, DS Goldman, JW Chiorean, EG Strother, RM Seon, BK Figg, WD Peer, CJ Alvarez, D Adams, BJ Theuer, CP Rosen, LS AF Gordon, Michael S. Robert, Francisco Matei, Daniela Mendelson, David S. Goldman, Jonathan W. Chiorean, E. Gabriela Strother, Robert M. Seon, Ben K. Figg, William D. Peer, Cody J. Alvarez, Delia Adams, Bonne J. Theuer, Charles P. Rosen, Lee S. TI An Open-Label Phase Ib Dose-Escalation Study of TRC105 (Anti-Endoglin Antibody) with Bevacizumab in Patients with Advanced Cancer SO CLINICAL CANCER RESEARCH LA English DT Article ID ENDOTHELIAL GROWTH-FACTOR; HEREDITARY HEMORRHAGIC TELANGIECTASIA; MICROVESSEL DENSITY; CD105 EXPRESSION; HEPATOCELLULAR-CARCINOMA; MONOCLONAL-ANTIBODY; PROGNOSTIC MARKERS; TUMOR VASCULATURE; COLORECTAL-CANCER; THERAPY AB Purpose: Endoglin, an endothelial cell membrane receptor expressed on angiogenic tumor vessels, is essential for angiogenesis and upregulated in the setting of VEGF inhibition. TRC105 is an anti-endoglin IgG1 monoclonal antibody that potentiates VEGF inhibitors in preclinical models. This study assessed safety, pharmacokinetics, and antitumor activity of TRC105 in combination with bevacizumab. Experimental Design: Patients (n = 38) with advanced solid tumors, Eastern Cooperative Group performance status 0-1, and normal organ function were treated with escalating doses of TRC105 plus bevacizumab until disease progression or unacceptable toxicity using a standard 3 + 3 phase I design. Results: TRC105 and bevacizumab were well tolerated at their recommended single-agent doses (10 mg/kg) when the initial dose of TRC105 was delayed by one week and divided over 2 days to limit the frequency of headache. The concurrent administration of bevacizumab and TRC105 did not otherwise potentiate known toxicities of TRC105 or bevacizumab. Hypertension and proteinuria were observed, though not at rates expected for single-agent bevacizumab. Several patients who had previously progressed on bevacizumab or VEGF receptor tyrosine kinase inhibitor (VEGFR TKI) treatment experienced reductions in tumor volume, including two partial responses by RECIST, and 6 remained without progression for longer periods than during their prior VEGF inhibitor therapy. Conclusions: TRC105 was well tolerated with bevacizumab and clinical activity was observed in a VEGF inhibitor- refractory population. Ongoing clinical trials are testing TRC105 in combination with bevacizumab in glioblastoma and with VEGFR TKIs in renal cell carcinoma, hepatocellular carcinoma, and soft tissue sarcoma. C1 [Gordon, Michael S.; Mendelson, David S.] Pinnacle Oncol Hematol, Scottsdale, AZ 85258 USA. [Robert, Francisco] Univ Alabama Birmingham, Birmingham, AL USA. [Matei, Daniela; Chiorean, E. Gabriela; Strother, Robert M.] Indiana Univ Sch Med, Indianapolis, IN 46202 USA. [Goldman, Jonathan W.; Rosen, Lee S.] Univ Calif Los Angeles, Dept Med, Los Angeles, CA 90024 USA. [Chiorean, E. Gabriela] Univ Washington, Seattle, WA 98195 USA. [Seon, Ben K.] Roswell Pk Canc Inst, Buffalo, NY 14263 USA. [Figg, William D.; Peer, Cody J.] NCI, Clin Pharmacol Program, Bethesda, MD 20892 USA. [Alvarez, Delia; Adams, Bonne J.; Theuer, Charles P.] TRACON Pharmaceut, San Diego, CA USA. RP Gordon, MS (reprint author), Pinnacle Oncol Hematol, 9055 E Del Camino,Suite 100, Scottsdale, AZ 85258 USA. EM mgordon@azpoh.com RI Figg Sr, William/M-2411-2016; OI Strother, Robert Matthew/0000-0001-8118-8954 FU TRACON Pharmaceuticals Inc; Center for Cancer Research of the National Cancer Institute; National Cancer Institute; NIH [HHSN261200800001E] FX This research was supported by TRACON Pharmaceuticals Inc and the Center for Cancer Research of the National Cancer Institute. This study has also been funded in whole or in part with federal funds from the National Cancer Institute, NIH, under contract number HHSN261200800001E. NR 40 TC 17 Z9 18 U1 1 U2 11 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1078-0432 EI 1557-3265 J9 CLIN CANCER RES JI Clin. Cancer Res. PD DEC 1 PY 2014 VL 20 IS 23 BP 5918 EP 5926 DI 10.1158/1078-0432.CCR-14-1143 PG 9 WC Oncology SC Oncology GA AW7AS UT WOS:000346417400009 PM 25261556 ER PT J AU Hassan, R Kindler, HL Jahan, T Bazhenova, L Reck, M Thomas, A Pastan, I Parno, J O'Shannessy, DJ Fatato, P Maltzman, JD Wallin, BA AF Hassan, Raffit Kindler, Hedy L. Jahan, Thierry Bazhenova, Lyudmila Reck, Martin Thomas, Anish Pastan, Ira Parno, Jeff O'Shannessy, Daniel J. Fatato, Penny Maltzman, Julia D. Wallin, Bruce A. TI Phase II Clinical Trial of Amatuximab, a Chimeric Antimesothelin Antibody with Pemetrexed and Cisplatin in Advanced Unresectable Pleural Mesothelioma SO CLINICAL CANCER RESEARCH LA English DT Article ID MEGAKARYOCYTE POTENTIATING FACTOR; MALIGNANT MESOTHELIOMA; MONOCLONAL-ANTIBODY; OVARIAN-CANCER; TUMOR-MARKER; SOLUBLE MESOTHELIN; EXPRESSION; SERUM; ADENOCARCINOMAS; OSTEOPONTIN AB Purpose: Amatuximab is a chimeric monoclonal antibody to mesothelin, a cell surface glycoprotein highly expressed in malignant pleural mesothelioma (MPM). On the basis of its synergy with chemotherapy in preclinical studies, we evaluated the antitumor activity of amatuximab plus pemetrexed and cisplatin in patients with unresectable MPM. Experimental Design: In a single-arm phase II study, amatuximab (5 mg/kg) was administered on days 1 and 8 with pemetrexed (500 mg/m(2)) and cisplatin (75 mg/m(2)) on day 1 of 21-day cycles for up to six cycles. Patients with response or stable disease received amatuximab maintenance until disease progression. Primary endpoint was progression-free survival (PFS) at 6 months. Secondary endpoints were overall survival (OS), response rate, and safety. Results: Eighty-nine patients were enrolled at 26 centers. Median of five cycles (range, 1-6) of combination treatment was administered, and 56 (63%) patients received amatuximab maintenance. Combination therapy resulted in no overlapping toxicities. Eleven patients (12.4%) had amatuximabrelated hypersensitivity reactions. Responses included partial responses in 33 (40%) and stable disease in 42 (51%). Six-month PFS rate was 51% [95% confidence interval (CI), 39.1-62.3)], median PFS was 6.1 months (95% CI, 5.8-6.4), and median OS was 14.8 months (95% CI, 12.4-18.5) with 29 patients alive at data cut-off. Conclusions: Amatuximab with pemetrexed and cisplatin was well tolerated with objective tumor response or stable disease rate of 90% by independent radiologic review. Although PFS was not significantly different from historical controls, the median OS was 14.8 months with a third of patients alive and 5 continuing to receive amatuximab at the time of analysis. C1 [Hassan, Raffit; Thomas, Anish] NCI, Thorac & GI Oncol Branch, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. [Kindler, Hedy L.] Univ Chicago, Chicago, IL 60637 USA. [Jahan, Thierry] Univ Calif San Francisco, San Francisco, CA 94143 USA. [Bazhenova, Lyudmila] Univ Calif San Diego, San Diego, CA 92103 USA. [Reck, Martin] Lung Clin Grosshansdorf, Dept Thorac Oncol, Grosshansdorf, Stormarn, Germany. [Pastan, Ira] NCI, Mol Biol Lab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. [Parno, Jeff] United BioSource Corp, Blue Bell, PA USA. [O'Shannessy, Daniel J.; Fatato, Penny; Maltzman, Julia D.; Wallin, Bruce A.] Morphotek Inc, Exton, PA USA. RP Hassan, R (reprint author), NCI, NIH, Bethesda, MD 20892 USA. EM hassanr@mail.nih.gov OI Thomas, Anish/0000-0003-3293-3115 FU Intramural Research Program of the NIH; National Cancer Institute; Morphotek, Inc.; Cooperative Research and Development Agreement; NCI FX This research was supported in part by the Intramural Research Program of the NIH, National Cancer Institute, Center for Cancer Research, and in part by Morphotek, Inc., under a Cooperative Research and Development Agreement with the NCI. NR 33 TC 30 Z9 30 U1 2 U2 3 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1078-0432 EI 1557-3265 J9 CLIN CANCER RES JI Clin. Cancer Res. PD DEC 1 PY 2014 VL 20 IS 23 BP 5927 EP 5936 DI 10.1158/1078-0432.CCR-14-0804 PG 10 WC Oncology SC Oncology GA AW7AS UT WOS:000346417400010 PM 25231400 ER PT J AU Kim, EJ Sahai, V Abel, EV Griffith, KA Greenson, JK Takebe, N Khan, GN Blau, JL Craig, R Balis, UG Zalupski, MM Simeone, DM AF Kim, Edward J. Sahai, Vaibhav Abel, Ethan V. Griffith, Kent A. Greenson, Joel K. Takebe, Naoko Khan, Gazala N. Blau, John L. Craig, Ronald Balis, Ulysses G. Zalupski, Mark M. Simeone, Diane M. TI Pilot Clinical Trial of Hedgehog Pathway Inhibitor GDC-0449 (Vismodegib) in Combination with Gemcitabine in Patients with Metastatic Pancreatic Adenocarcinoma SO CLINICAL CANCER RESEARCH LA English DT Article ID PHASE-III TRIAL; DUCTAL ADENOCARCINOMA; 1ST-LINE TREATMENT; PLUS GEMCITABINE; ONCOLOGY-GROUP; CANCER; SURVIVAL; THERAPY; STROMA AB Purpose: The hedgehog (HH) signaling pathway is a key regulator in tumorigenesis of pancreatic adenocarcinoma and is upregulated in pancreatic adenocarcinoma cancer stem cells (CSCs). GDC-0449 is an oral small-molecule inhibitor of the HH pathway. This study assessed the effect of GDC-0449-mediated HH inhibition in paired biopsies, followed by combined treatment with gemcitabine, in patients with metastatic pancreatic adenocarcinoma. Experimental Design: Twenty-five patients were enrolled of which 23 underwent core biopsies at baseline and following 3 weeks of GDC-0449. On day 29, 23 patients started weekly gemcitabine while continuing GDC-0449. We evaluated GLI1 and PTCH1 inhibition, change in CSCs, Ki-67, fibrosis, and assessed tumor response, survival and toxicity. Results: On pretreatment biopsy, 75% of patients had elevated sonic hedgehog (SHH) expression. On posttreatment biopsy, GLI1 and PTCH1 decreased in 95.6% and 82.6% of 23 patients, fibrosis decreased in 45.4% of 22, and Ki-67 in 52.9% of 17 evaluable patients. No significant changes were detected in CSCs pre-and postbiopsy. The median progression-free and overall survival for all treated patients were 2.8 and 5.3 months. The response and disease control rate was 21.7% and 65.2%. No significant correlation was noted between CSCs, fibrosis, SHH, Ki-67, GLI1, PTCH1 (baseline values or relative change on posttreatment biopsy), and survival. Grade >= 3 adverse events were noted in 56% of patients. Conclusion: We show that GDC-0449 for 3 weeks leads to downmodulation of GLI1 and PTCH1, without significant changes in CSCs compared with baseline. GDC-0449 and gemcitabine were not superior to gemcitabine alone in the treatment of metastatic pancreatic cancer. (C) 2014 AACR. C1 [Kim, Edward J.; Sahai, Vaibhav; Khan, Gazala N.; Zalupski, Mark M.] Univ Michigan, Div Hematol Oncol, Dept Internal Med, Ann Arbor, MI 48109 USA. [Sahai, Vaibhav; Abel, Ethan V.; Simeone, Diane M.] Univ Michigan, Translat Oncol Program, Ann Arbor, MI 48109 USA. [Griffith, Kent A.] Univ Michigan, Sch Publ Hlth, Ctr Canc Biostat, Ann Arbor, MI 48109 USA. [Greenson, Joel K.; Blau, John L.; Craig, Ronald; Balis, Ulysses G.] Univ Michigan, Dept Pathol, Ann Arbor, MI 48109 USA. [Takebe, Naoko] NCI, Div Canc Treatment & Diag, Bethesda, MD 20892 USA. RP Simeone, DM (reprint author), Univ Michigan, Translat Oncol Program, 1500 E Med Ctr Dr, Ann Arbor, MI 48109 USA. EM simeone@med.umich.edu FU NIH through the University of Michigan's Cancer Center Support Grant [5 P30 CA046592]; Cancer Center Clinical Trials Office Core; Michigan Institute for Clinical and Health Research Pilot Grant [ULRR024986] FX This work was supported (in part) by the NIH through the University of Michigan's Cancer Center Support Grant (5 P30 CA046592) by the use of the Cancer Center Clinical Trials Office Core and also supported (in part) by a Michigan Institute for Clinical and Health Research Pilot Grant (ULRR024986). NR 27 TC 48 Z9 49 U1 1 U2 16 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1078-0432 EI 1557-3265 J9 CLIN CANCER RES JI Clin. Cancer Res. PD DEC 1 PY 2014 VL 20 IS 23 BP 5937 EP 5945 DI 10.1158/1078-0432.CCR-14-1269 PG 9 WC Oncology SC Oncology GA AW7AS UT WOS:000346417400011 PM 25278454 ER PT J AU Huestis, MA AF Huestis, Marilyn A. TI Untitled SO CLINICAL CHEMISTRY LA English DT Editorial Material C1 [Huestis, Marilyn A.] NIDA, Baltimore, MD 21224 USA. RP Huestis, MA (reprint author), NIDA, Biomed Res Ctr, 251 Bayview Blvd,Suite 200,Rm 05A-721, Baltimore, MD 21224 USA. EM mhuestis@intra.nida.nih.gov NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER ASSOC CLINICAL CHEMISTRY PI WASHINGTON PA 2101 L STREET NW, SUITE 202, WASHINGTON, DC 20037-1526 USA SN 0009-9147 EI 1530-8561 J9 CLIN CHEM JI Clin. Chem. PD DEC PY 2014 VL 60 IS 12 BP 1484 EP 1485 DI 10.1373/clinchem.2014.224543 PG 3 WC Medical Laboratory Technology SC Medical Laboratory Technology GA AW7CS UT WOS:000346422800008 PM 25432994 ER PT J AU Vuppalanchi, R Jain, AK Deppe, R Yates, K Comerford, M Masuoka, HC Neuschwander-Tetri, BA Loomba, R Brunt, EM Kleiner, DE Molleston, JP Schwimmer, JB Lavine, JE Tonascia, J Chalasani, N AF Vuppalanchi, Raj Jain, Ajay K. Deppe, Ross Yates, Katherine Comerford, Megan Masuoka, Howard C. Neuschwander-Tetri, Brent A. Loomba, Rohit Brunt, Elizabeth M. Kleiner, David E. Molleston, Jean P. Schwimmer, Jeffrey B. Lavine, Joel E. Tonascia, James Chalasani, Naga TI Relationship Between Changes in Serum Levels of Keratin 18 and Changes in Liver Histology in Children and Adults With Nonalcoholic Fatty Liver Disease SO CLINICAL GASTROENTEROLOGY AND HEPATOLOGY LA English DT Article DE Serum K18; Noninvasive Biomarker; Nonalcoholic Steatohepatitis; PIVENS; TONIC ID VITAMIN-E; CYTOKERATIN-18 FRAGMENTS; PLASMA CYTOKERATIN-18; HEPATIC STEATOSIS; STEATOHEPATITIS; PREVALENCE; APOPTOSIS; PIOGLITAZONE; EPIDEMIOLOGY; POPULATION AB BACKGROUND & AIMS: Cross-sectional studies have associated serum levels of the keratin 18 (K18) fragment with histologic features of liver in individuals with nonalcoholic fatty liver disease (NAFLD). We investigated the relationship between changes in serum levels of K18 and changes in liver histology in adults and children with NAFLD. METHODS: We measured levels of K18 in stored serum samples collected at baseline and various time points from 231 adults with nonalcoholic steatohepatitis and 152 children with NAFLD who participated in 2 separate prospective randomized clinical trials. Liver biopsy specimens collected at baseline and week 96 were reviewed centrally. RESULTS: There were greater decreases in serum levels of K18 in adults with histologic improvement at week 96 than in those without histologic improvement at week 16 (decrease, 193 +/- 293 vs 139 +/- 467 U/L; P < .001), week 48 (decrease, 232 +/- 360 vs 113 +/- 425 U/L; P < .001), or week 96 (decrease, 269 +/- 368 vs 97 +/- 400 U/L; P < .001). There were greater decreases in serum levels of K18 in children with histologic improvements than in those without histologic improvements at week 48 (decrease, 197 +/- 467 vs 47 +/- 350 U/L; P = .005) and week 96 (decrease, 206 +/- 432 vs 2 +/- 474 U/L; P < .001). However, reductions in serum levels of K18 were not better than reductions in levels of alanine aminotransferase in identifying adults with histologic improvement (area under the receiver operator characteristic [AUROC], 0.71; 95% confidence interval [CI], 0.63-0.80; vs AUROC, 0.68; 95% CI, 0.61-0.79; P = .34) or children (AUROC, 0.72; 95% CI, 0.63-0.81; vs AUROC, 0.79; 95% CI, 0.70-0.87; P = .42). CONCLUSIONS: Decreases in serum levels of K18 are associated strongly with improved liver histologies in adults or children with NAFLD. However, reductions in K18 do not perform better than those in alanine aminotransferase level in identifying histologic changes in NAFLD. C1 [Vuppalanchi, Raj; Deppe, Ross; Comerford, Megan; Masuoka, Howard C.; Molleston, Jean P.; Chalasani, Naga] Indiana Univ Sch Med, Dept Med, Indianapolis, IN 46202 USA. [Jain, Ajay K.; Neuschwander-Tetri, Brent A.] St Louis Univ, St Louis, MO 63103 USA. [Yates, Katherine; Tonascia, James] Johns Hopkins Univ, Bloomberg Sch Publ Hlth, Baltimore, MD USA. [Loomba, Rohit] Univ Calif San Diego, Div Gastroenterol, San Diego, CA 92103 USA. [Schwimmer, Jeffrey B.] Univ Calif San Diego, Dept Pediat, San Diego, CA 92103 USA. [Brunt, Elizabeth M.] Washington Univ, Sch Med, St Louis, MO USA. [Kleiner, David E.] NCI, Pathol Lab, Bethesda, MD 20892 USA. [Schwimmer, Jeffrey B.] Rady Childrens Hosp, Dept Gastroenterol, San Diego, CA USA. [Lavine, Joel E.] Columbia Univ, Dept Pediat, New York, NY 10027 USA. RP Chalasani, N (reprint author), Indiana Univ Sch Med, Div Gastroenterol & Hepatol, 1050 Wishard Blvd,RG 4100, Indianapolis, IN 46202 USA. EM nchalasa@iu.edu OI Vuppalanchi, Raj/0000-0003-0637-1577 FU American Recovery and Reinvestment Act [3K24DK069290-05S1] FX Supported in part by an award from the American Recovery and Reinvestment Act of 2009 ( 3K24DK069290-05S1 to N.C.). NR 33 TC 12 Z9 12 U1 0 U2 4 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1542-3565 EI 1542-7714 J9 CLIN GASTROENTEROL H JI Clin. Gastroenterol. Hepatol. PD DEC PY 2014 VL 12 IS 12 BP 2121 EP U416 DI 10.1016/j.cgh.2014.05.010 PG 12 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA AW6FA UT WOS:000346363600029 PM 24846279 ER PT J AU Lauer, MS AF Lauer, Michael S. TI Clinical trials in crisis: Four simple methodologic fixes Commentary SO CLINICAL TRIALS LA English DT Editorial Material ID HEALTH-CARE; GISSI; STORY; LUNG C1 NHLBI, Div Cardiovasc Sci DCVS, Bethesda, MD 20892 USA. RP Lauer, MS (reprint author), NHLBI, Div Cardiovasc Sci DCVS, Bldg 10, Bethesda, MD 20892 USA. EM lauerm@nhlbi.nih.gov FU Intramural NIH HHS [Z99 HL999999] NR 16 TC 0 Z9 0 U1 0 U2 1 PU SAGE PUBLICATIONS LTD PI LONDON PA 1 OLIVERS YARD, 55 CITY ROAD, LONDON EC1Y 1SP, ENGLAND SN 1740-7745 EI 1740-7753 J9 CLIN TRIALS JI Clin. Trials PD DEC PY 2014 VL 11 IS 6 BP 622 EP 623 DI 10.1177/1740774514553482 PG 2 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA AW6QU UT WOS:000346394500002 PM 25389225 ER PT J AU Meert, K Keele, L Clark, A AF Meert, Kathleen Keele, Linda Clark, Amy CA Collaborative Pediat Critical Care TI VARIABILITY IN END-OF-LIFE PRACTICE AMONG US TERTIARY CARE PEDIATRIC INTENSIVE CARE UNITS (PICUS) SO CRITICAL CARE MEDICINE LA English DT Meeting Abstract C1 [Meert, Kathleen] Wayne State Univ, Detroit, MI USA. [Keele, Linda; Clark, Amy] Univ Utah, Salt Lake City, UT USA. [Collaborative Pediat Critical Care] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Bethesda, 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 0090-3493 EI 1530-0293 J9 CRIT CARE MED JI Crit. Care Med. PD DEC PY 2014 VL 42 IS 12 SU S MA 389 PG 1 WC Critical Care Medicine SC General & Internal Medicine GA AW3UP UT WOS:000346211800354 ER PT J AU Pollack, M Holubkov, R Tomohiko, F AF Pollack, Murray Holubkov, Richard Tomohiko, Funai CA CPCCRN TI SIMULTANEOUS PREDICTION OF MORBIDITY (M), MORTALITY (D), AND INTACT SURVIVAL (S) SO CRITICAL CARE MEDICINE LA English DT Meeting Abstract C1 [Pollack, Murray] Childrens Natl Hlth Syst, Washington, DC USA. [Holubkov, Richard; Tomohiko, Funai] Univ Utah, Salt Lake City, UT USA. [CPCCRN] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, 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 0090-3493 EI 1530-0293 J9 CRIT CARE MED JI Crit. Care Med. PD DEC PY 2014 VL 42 IS 12 SU S MA 373 PG 1 WC Critical Care Medicine SC General & Internal Medicine GA AW3UP UT WOS:000346211800338 ER PT J AU Kost, RG Lee, LN Yessis, JL Wesley, R Alfano, S Alexander, SR Kassis, SB Cola, P Dozier, A Ford, DE Harris, PA Kim, E Lee, SC O'Riordan, G Roth, MT Schuff, K Wasser, J Henderson, DK Coller, BS AF Kost, Rhonda G. Lee, Laura N. Yessis, Jennifer L. Wesley, Robert Alfano, Sandra Alexander, Steven R. Kassis, Sylvia Baedorf Cola, Philip Dozier, Ann Ford, Dan E. Harris, Paul A. Kim, Emmelyn Lee, Simon Craddock O'Riordan, Gerri Roth, Mary-Tara Schuff, Kathryn Wasser, June Henderson, David K. Coller, Barry S. TI Research Participant-Centered Outcomes at NIH-Supported Clinical Research Centers SO CTS-CLINICAL AND TRANSLATIONAL SCIENCE LA English DT Article DE patient-centered outcomes research; translational research; patient satisfaction; outcomes research; clinical trials ID CARE-SYSTEM DISTRUST; HOSPITAL SURVEY; PERCEPTION; RETURN AB BackgroundAlthough research participation is essential for clinical investigation, few quantitative outcome measures exist to assess participants' experiences. To address this, we developed and deployed a survey at 15 NIH-supported clinical research centers to assess participant-centered outcomes; we report responses from 4,961 participants. MethodsSurvey questions addressed core aspects of the research participants' experience, including their overall rating, motivation, trust, and informed consent. We describe participant characteristics, responses to individual questions, and correlations among responses. ResultsRespondents broadly represented the research population in sex, race, and ethnicity. Seventy-three percent awarded top ratings to their overall research experience and 94% reported no pressure to enroll. Top ratings correlated with feeling treated with respect, listened to, and having access to the research team (R-2 = 0.80-0.96). White participants trusted researchers more (88%) than did nonwhite participants collectively (80%; p < 0.0001). Many participants felt fully prepared by the informed consent process (67%) and wanted to receive research results (72%). ConclusionsOur survey demonstrates that a majority of participants at NIH-supported clinical research centers rate their research experience very positively and that participant-centered outcome measures identify actionable items for improvement of participant's experiences, research protections, and the conduct of clinical investigation. C1 [Kost, Rhonda G.; Coller, Barry S.] Rockefeller Univ, Ctr Clin Translat Sci, New York, NY 10021 USA. [Lee, Laura N.; Wesley, Robert; Henderson, David K.] NIH, Off Deputy Director Clin Care, Ctr Clin, Bethesda, MD 20892 USA. [Yessis, Jennifer L.] Univ Waterloo, Propel Ctr Populat Hlth, Waterloo, ON N2L 3G1, Canada. [Alfano, Sandra] Yale Univ, Human Invest Comm, New Haven, CT USA. [Alexander, Steven R.; O'Riordan, Gerri] Stanford Univ, Spectrum Stanford Univ Ctr Clin & Translat Educ &, Palo Alto, CA 94304 USA. [Kassis, Sylvia Baedorf; Roth, Mary-Tara] Boston Univ, Clin & Translat Sci Inst, Boston, MA 02215 USA. [Cola, Philip] Univ Hosp Case Med Ctr, Cleveland, OH USA. [Cola, Philip] Case Western Reserve Univ, Sch Med, Cleveland, OH USA. [Dozier, Ann] Univ Rochester, Rochester, NY USA. [Ford, Dan E.] Johns Hopkins Inst Clin Translat Res, Baltimore, MD USA. [Harris, Paul A.] Vanderbilt Univ, Vanderbilt Inst Clin & Translat Res, Nashville, TN 37235 USA. [Kim, Emmelyn] North Shore LIJ Hlth Syst, Feinstein Inst Med Res, Manhasset, NY USA. [Lee, Simon Craddock] Univ Texas SW Med Ctr Dallas, Dept Clin Sci, Dallas, TX 75390 USA. [Schuff, Kathryn] Oregon Hlth & Sci Univ, Portland, OR 97201 USA. [Wasser, June] Tufts Univ, Sch Med, Boston, MA 02111 USA. RP Kost, RG (reprint author), Rockefeller Univ, Ctr Clin Translat Sci, 1230 York Ave, New York, NY 10021 USA. EM kostr@rockefeller.edu OI Lee, Simon J. Craddock/0000-0001-6345-1237 FU National Center for Research Resources (NCRR) [UL1TR000043, UL1TR000157, UL1TR000128, UL1TR000093, 1-U54-AI108332-01, UL1TR000445, UL1TR001085, UL1RR024143, UL1TR001064, UL1TR000073, UL1TR000439, UL1TR001105, UL1RR024160, UL1RR024128, UL1TR00111]; National Center for Advancing Translational Sciences (NCATS), National Institutes of Health FX Supported in part by grants UL1TR000043, UL1TR000157, UL1TR000128, UL1TR000093, 1-U54-AI108332-01, UL1TR000445, UL1TR001085, UL1RR024143, UL1TR001064, UL1TR000073, UL1TR000439, UL1TR001105, UL1RR024160, UL1RR024128, and UL1TR00111 from the National Center for Research Resources (NCRR) and the National Center for Advancing Translational Sciences (NCATS), National Institutes of Health. NR 35 TC 1 Z9 1 U1 1 U2 3 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1752-8054 EI 1752-8062 J9 CTS-CLIN TRANSL SCI JI CTS-Clin. Transl. Sci. PD DEC PY 2014 VL 7 IS 6 BP 430 EP 440 DI 10.1111/cts.12167 PG 11 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA AW5CD UT WOS:000346292600002 PM 24842076 ER PT J AU Zhao, GH Blackstone, C AF Zhao, Guohua Blackstone, Craig TI ER Morphology: Sculpting with XendoU SO CURRENT BIOLOGY LA English DT Editorial Material ID ENDOPLASMIC-RETICULUM; NETWORK FORMATION; FAMILY C1 [Zhao, Guohua; Blackstone, Craig] NINDS, Cell Biol Sect, Neurogenet Branch, NIH, Bethesda, MD 20892 USA. RP Blackstone, C (reprint author), NINDS, Cell Biol Sect, Neurogenet Branch, NIH, Bldg 35,Room 2C-913,9000 Rockville Pike, Bethesda, MD 20892 USA. EM blackstc@ninds.nih.gov NR 20 TC 0 Z9 0 U1 1 U2 6 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 0960-9822 EI 1879-0445 J9 CURR BIOL JI Curr. Biol. PD DEC PY 2014 VL 24 IS 24 DI 10.1016/j.cub.2014.11.005 PG 4 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA AW9ME UT WOS:000346580700014 PM 25514011 ER PT J AU Burns, DN Grossman, C Turpin, J Elharrar, V Veronese, F AF Burns, David N. Grossman, Cynthia Turpin, Jim Elharrar, Vanessa Veronese, Fulvia TI Role of Oral Pre-exposure Prophylaxis (PrEP) in Current and Future HIV Prevention Strategies SO CURRENT HIV/AIDS REPORTS LA English DT Article DE HIV/human immunodeficiency virus; Prevention; PrEP/pre-exposure prophylaxis; ARVs/antiretrovirals ID TENOFOVIR DISOPROXIL FUMARATE; FEMALE GENITAL-TRACT; UNITED-STATES; COST-EFFECTIVENESS; ANTIRETROVIRAL THERAPY; TOPICAL MICROBICIDES; MATHEMATICAL-MODELS; INTERIM GUIDANCE; HETEROSEXUAL MEN; DRUG-RESISTANCE AB Treatment as prevention is expected to have a major role in reducing HIV incidence, but other prevention interventions will also be required to bring the epidemic under control, particularly among key populations. One or more forms of pre-exposure prophylaxis (PrEP) will likely play a critical role. Oral PrEP with emtricitabine-tenofovir (TruvadaA (R)) is currently available in the US and some other countries, but uptake has been slow. We review the concerns that have contributed to this slow uptake and discuss current and future research in this critical area of HIV prevention research. C1 [Burns, David N.; Turpin, Jim; Elharrar, Vanessa; Veronese, Fulvia] NIAID, Div Aids, NIH, Bethesda, MD 20892 USA. [Grossman, Cynthia] NIMH, Div Aids, NIH, Bethesda, MD 20892 USA. RP Burns, DN (reprint author), NIAID, Div Aids, NIH, 5601 Fishers Lane,MSC 9831, Bethesda, MD 20892 USA. EM burnsda@niaid.nih.gov NR 81 TC 7 Z9 7 U1 3 U2 22 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1548-3568 EI 1548-3576 J9 CURR HIV-AIDS REP JI Curr. Hiv/Aids Rep. PD DEC PY 2014 VL 11 IS 4 BP 393 EP 403 DI 10.1007/s11904-014-0234-8 PG 11 WC Infectious Diseases SC Infectious Diseases GA AW4IY UT WOS:000346245800003 PM 25283184 ER PT J AU Bezrukov, SM Schimansky-Geier, L Schmid, G AF Bezrukov, S. M. Schimansky-Geier, L. Schmid, G. TI Brownian motion in confined geometries SO EUROPEAN PHYSICAL JOURNAL-SPECIAL TOPICS LA English DT Editorial Material ID DIFFUSION; TRANSPORT; CHANNEL AB In a great number of technologically and biologically relevant cases, transport of micro- or nanosized objects is governed by both omnipresent thermal fluctuations and confining walls or constrictions limiting the available phase space. The present Topical Issue covers the most recent applications and theoretical findings devoted to studies of Brownian motion under confinement of channel-like geometries. C1 [Bezrukov, S. M.] NICHD, Program Phys Biol, NIH, Bethesda, MD 20892 USA. [Schimansky-Geier, L.] Humboldt Univ, Inst Phys, D-12489 Berlin, Germany. [Schmid, G.] Univ Augsburg, Inst Phys, D-86159 Augsburg, Germany. RP Bezrukov, SM (reprint author), NICHD, Program Phys Biol, NIH, Bethesda, MD 20892 USA. EM bezrukos@mail.nih.gov; alsg@physik.hu-berlin.de; Gerhard.Schmid@physik.uni-augsburg.de NR 41 TC 1 Z9 1 U1 3 U2 24 PU SPRINGER HEIDELBERG PI HEIDELBERG PA TIERGARTENSTRASSE 17, D-69121 HEIDELBERG, GERMANY SN 1951-6355 EI 1951-6401 J9 EUR PHYS J-SPEC TOP JI Eur. Phys. J.-Spec. Top. PD DEC PY 2014 VL 223 IS 14 BP 3021 EP 3025 DI 10.1140/epjst/e2014-02316-6 PG 5 WC Physics, Multidisciplinary SC Physics GA AW7AI UT WOS:000346416400001 ER PT J AU Berezhkovskii, AM Bezrukov, SM AF Berezhkovskii, A. M. Bezrukov, S. M. TI On the applicability of entropy potentials in transport problems SO EUROPEAN PHYSICAL JOURNAL-SPECIAL TOPICS LA English DT Review ID FACILITATED MEMBRANE-TRANSPORT; CHANNEL; DIFFUSION; VDAC; TUBULIN AB Transport in confined structures of varying geometry has become the subject of growing attention in recent years since such structures are ubiquitous in biology and technology. In analyzing transport in systems of this type, the notion of entropy potentials is widely used. Entropy potentials naturally arise in one-dimensional description of equilibrium distributions in multidimensional confined structures. However, their application to transport problems requires some caution. In this article we discuss such applications and summarize the results of recent studies exploring the limits of applicability. We also consider an example of a transport problem in a system of varying geometry, where the conventional approach is inapplicable since the geometry changes abruptly. In addition, we demonstrate how the entropy potential can be used to analyze optimal transport through a three-dimensional cosine-shaped channel. C1 [Berezhkovskii, A. M.; Bezrukov, S. M.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Program Phys Biol, NIH, Bethesda, MD 20892 USA. [Berezhkovskii, A. M.] NIH, Math & Stat Comp Lab, Div Computat Biosci, Ctr Informat Technol, Bethesda, MD 20892 USA. RP Berezhkovskii, AM (reprint author), Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Program Phys Biol, NIH, Bethesda, MD 20892 USA. FU NIH, Center for Information Technology; Eunice Kennedy Shriver National Institute of Child Health and Human Development FX This study was supported by the Intramural Research Program of the NIH, Center for Information Technology and Eunice Kennedy Shriver National Institute of Child Health and Human Development. NR 36 TC 6 Z9 6 U1 1 U2 10 PU SPRINGER HEIDELBERG PI HEIDELBERG PA TIERGARTENSTRASSE 17, D-69121 HEIDELBERG, GERMANY SN 1951-6355 EI 1951-6401 J9 EUR PHYS J-SPEC TOP JI Eur. Phys. J.-Spec. Top. PD DEC PY 2014 VL 223 IS 14 BP 3063 EP 3077 DI 10.1140/epjst/e2014-02319-3 PG 15 WC Physics, Multidisciplinary SC Physics GA AW7AI UT WOS:000346416400004 PM 26339466 ER PT J AU Liang, XY Chen, LJ Ng, TK Tuo, J Gao, JL Tam, POS Lai, TYY Chan, CC Pang, CP AF Liang, X. Y. Chen, L. J. Ng, T. K. Tuo, J. Gao, J-L Tam, P. O. S. Lai, T. Y. Y. Chan, C-C Pang, C. P. TI FPR1 interacts with CFH, HTRA1 and smoking in exudative age-related macular degeneration and polypoidal choroidal vasculopathy SO EYE LA English DT Article ID FORMYL PEPTIDE RECEPTOR; PIGMENT EPITHELIAL-CELLS; FORMYLPEPTIDE RECEPTOR; BRUCHS MEMBRANE; FUNCTIONAL DOMAINS; ALZHEIMERS-DISEASE; ASSOCIATION; POLYMORPHISMS; INFLAMMATION; CHEMOTAXIS AB Purpose To determine the genetic association of an inflammation-related gene, formyl peptide receptor 1 (FPR1), in exudative age-related macular degeneration (AMD) and polypoidal choroidal vasculopathy (PCV). Methods The coding region of FPR1 gene was sequenced in 554 unrelated Chinese individuals: 155 exudative AMD patients, 179 PCV patients, and 220 controls. Interactions and combined effects of FPR1 with complement factor H (CFH), high temperature requirement factor A1 (HTRA1), and smoking were also investigated. Results A total of 28 polymorphisms in FPR1 were identified. Single nucleotide polymorphisms (SNP) rs78488639 increased the risk to exudative AMD (P = 0.043) and PCV (P = 0.016), whereas SNP rs867229 decreased the risk to exudative AMD (P = 0.0026), but not PCV. Homozygous G allele of rs1042229 was associated with exudative AMD (P = 0.0394, odds ratio (OR) = 2.27, 95% confident interval: 1.08-4.74), but not with PCV. Exudative AMD, but not PCV, was associated with the heterozygous genotypes of rs2070746 (P = 0.019, OR = 0.57) and rs867229 (P = 0.0082, OR = 0.54). Significantly, interactions were identified among FPR1 rs78488639, CFH rs800292, and HTRA1 rs11200638 in both exudative AMD and PCV. Combined heterozygous risk alleles of CFH rs800292 GA and FPR1 rs78488639 CA were posed to PCV (P = 2.22 x 10(-4), OR = 10.47), but not exudative AMD. Furthermore, FPR1 rs78488639 CA combining with HTRA1 rs11200638 and smoking was also predisposed risks to exudative AMD and PCV. Conclusion FPR1 is associated with exudative AMD and PCV in a Hong Kong Chinese cohort. FPR1 rs78488639 interacted with CFH rs800292, HTRA1 rs11200638, and smoking, enhancing risk to exudative AMD and PCV. C1 [Liang, X. Y.; Chen, L. J.; Ng, T. K.; Tam, P. O. S.; Lai, T. Y. Y.; Pang, C. P.] Chinese Univ Hong Kong, Dept Ophthalmol & Visual Sci, Hong Kong Eye Hosp, Kowloon, Hong Kong, Peoples R China. [Tuo, J.; Chan, C-C] NEI, Immunol Lab, NIH, Bethesda, MD 20892 USA. [Gao, J-L] NIAID, Lab Mol Immunol, NIH, Bethesda, MD 20892 USA. RP Pang, CP (reprint author), Chinese Univ Hong Kong, Dept Ophthalmol & Visual Sci, Hong Kong Eye Hosp, 4-F,147K Argyle St, Kowloon, Hong Kong, Peoples R China. EM cppang@cuhk.edu.hk OI Ng, Tsz Kin/0000-0001-7863-7229 FU Endowment Fund for Lim Por-Yen Eye Genetics Research Centre; Chinese University of Hong Kong; General Research Fund from the Research Grants Council, Hong Kong [473410] FX We express our greatest appreciation to all the study participants. This study was supported in part by the Endowment Fund for Lim Por-Yen Eye Genetics Research Centre, the Chinese University of Hong Kong and the General Research Fund from the Research Grants Council (grant number 473410), Hong Kong. NR 51 TC 2 Z9 2 U1 1 U2 2 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0950-222X EI 1476-5454 J9 EYE JI Eye PD DEC PY 2014 VL 28 IS 12 BP 1502 EP 1510 DI 10.1038/eye.2014.226 PG 9 WC Ophthalmology SC Ophthalmology GA AW6FQ UT WOS:000346365600015 PM 25277308 ER PT J AU Chen, J Teixeira, PF Glaser, E Levine, RL AF Chen, Jue Teixeira, Pedro Filipe Glaser, Elzbieta Levine, Rodney L. TI Mechanism of oxidative inactivation of human presequence protease by hydrogen peroxide SO FREE RADICAL BIOLOGY AND MEDICINE LA English DT Article DE Presequence protease; Protein oxidation; Peptide degradation; Cysteine oxidation; Methionine sulfoxide; Free radicals ID METHIONINE SULFOXIDE REDUCTASE; METAL-CATALYZED OXIDATION; ALZHEIMERS-DISEASE; ORGANELLAR PEPTIDASOME; PROTEINS; PREP; DEGRADATION; MITOCHONDRIA; PEROXIREDOXINS; QUANTITATION AB The mitochondrial presequence protease (PreP) is a member of the pitrilysin class of metalloproteases. It degrades the mitochondrial targeting presequences of mitochondria-localized proteins as well as unstructured peptides such as amyloid-beta peptide. The specific activity of PreP is reduced in Alzheimer patients and animal models of Alzheimer disease. The loss of activity can be mimicked in vitro by exposure to oxidizing conditions, and indirect evidence suggested that inactivation was due to methionine oxidation. We performed peptide mapping analyses to elucidate the mechanism of inactivation. None of the 24 methionine residues in recombinant human PreP was oxidized. We present evidence that inactivation is due to oxidation of cysteine residues and consequent oligomerization through intermolecular disulfide bonds. The most susceptible cysteine residues to oxidation are Cys34, Cys112, and Cys119. Most, but not all, of the activity loss is restored by the reducing agent dithiothreitol. These findings elucidate a redox mechanism for regulation of PreP and also provide a rational basis for therapeutic intervention in conditions characterized by excessive oxidation of PreP. Published by Elsevier Inc. C1 [Chen, Jue; Levine, Rodney L.] Natl Heart Lung & Blood Inst, Biochem Lab, Bethesda, MD 20892 USA. [Teixeira, Pedro Filipe; Glaser, Elzbieta] Stockholm Univ, Arrhenius Labs Nat Sci, Dept Biochem & Biophys, S-10691 Stockholm, Sweden. RP Levine, RL (reprint author), Natl Heart Lung & Blood Inst, Biochem Lab, Bethesda, MD 20892 USA. EM rlevine@nih.gov RI Levine, Rodney/D-9885-2011 FU Intramural Research Program of the National Heart, Lung, and Blood Institute; Swedish Research Council [621-2012-4713]; Swedish Alzheimer Foundation [03-067] FX This study was supported by the Intramural Research Program of the National Heart, Lung, and Blood Institute (J.C., R.L.L.) and by grants from the Swedish Research Council (621-2012-4713) and the Swedish Alzheimer Foundation (03-067) (to E.G.). NR 31 TC 1 Z9 1 U1 2 U2 5 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0891-5849 EI 1873-4596 J9 FREE RADICAL BIO MED JI Free Radic. Biol. Med. PD DEC PY 2014 VL 77 BP 57 EP 63 DI 10.1016/j.freeradbiomed.2014.08.016 PG 7 WC Biochemistry & Molecular Biology; Endocrinology & Metabolism SC Biochemistry & Molecular Biology; Endocrinology & Metabolism GA AW6QA UT WOS:000346392500007 PM 25236746 ER PT J AU Ono, K Akaike, T Sawa, T Kumagai, Y Wink, DA Tantillo, DJ Hobbs, AJ Nagy, P Xian, M Lin, J Fukuto, JM AF Ono, Katsuhiko Akaike, Takaaki Sawa, Tomohiro Kumagai, Yoshito Wink, David A. Tantillo, Dean J. Hobbs, Adrian J. Nagy, Peter Xian, Ming Lin, Joseph Fukuto, Jon M. TI Redox chemistry and chemical biology of H2S, hydropersulfides, and derived species: Implications of their possible biological activity and utility SO FREE RADICAL BIOLOGY AND MEDICINE LA English DT Review DE Hydrogen sulfide; Persulfides; Polysulfides; Thiols; Thiol redox ID PECTINATA BACTERIA SYMBIOSIS; PROTEIN S-SULFHYDRATION; SPERM-WHALE MYOGLOBIN; ANIMATION-LIKE STATE; HYDROGEN-SULFIDE; LUCINA-PECTINATA; OXIDATIVE STRESS; HEMOGLOBIN-I; REDUCTION POTENTIALS; ALIPHATIC DISULFIDES AB Hydrogen sulfide (H2S) is an endogenously generated and putative signaling/effector molecule. Despite its numerous reported functions, the chemistry by which it elicits its functions is not understood. Moreover, recent studies allude to the existence of other sulfur species besides H2S that may play critical physiological roles. Herein, the basic chemical biology of H2S as well as other related or derived species is discussed and reviewed. This review particularly focuses on the per- and polysulfides which are likely in equilibrium with free H2S and which may be important biological effectors themselves. (C) 2014 Elsevier Inc. All rights reserved. C1 [Ono, Katsuhiko; Fukuto, Jon M.] Sonoma State Univ, Dept Chem, Rohnert Pk, CA 94928 USA. [Akaike, Takaaki; Sawa, Tomohiro] Tohoku Univ, Grad Sch Med, Dept Environm Hlth Sci & Mol Toxicol, Sendai, Miyagi 9808575, Japan. [Kumagai, Yoshito] Univ Tsukuba, Grad Sch Comprehens Human Sci, Doctoral Program Biomed Sci, Tsukuba, Ibaraki 3058575, Japan. [Wink, David A.] NCI, Radiat Biol Branch, Tumor Biol Sect, Bethesda, MD 20892 USA. [Tantillo, Dean J.] Univ Calif Davis, Dept Chem, Davis, CA 95616 USA. [Hobbs, Adrian J.] Queen Mary Univ London, Bart & London Sch Med, William Harvey Res Inst, London EC1M 6BQ, England. [Nagy, Peter] Natl Inst Oncol, Dept Mol Immunol & Toxicol, Budapest, Hungary. [Xian, Ming] Washington State Univ, Dept Chem, Pullman, WA 99164 USA. [Lin, Joseph] Sonoma State Univ, Dept Biol, Rohnert Pk, CA 94928 USA. RP Fukuto, JM (reprint author), Sonoma State Univ, Dept Chem, Rohnert Pk, CA 94928 USA. EM fukuto@sonoma.edu RI Nagy, Peter/C-6768-2008 OI Nagy, Peter/0000-0003-3393-235X FU Marie Curie International Reintegration Grant [PIRG08-GA-2010-277006] FX P.N. is grateful for financial support from FP7-PEOPLE-2010-RG (Marie Curie International Reintegration Grant PIRG08-GA-2010-277006) and The Hungarian National Science Foundation (OTKA; Grant K109843). The authors also acknowledge support from the NIH (HL106598 to J.M.F.; R01HL116571 to M.X.), NSF (CHE-1148641 to J.M.F.), and ACS-PRF (52801-ND4 to D.J.T.). T.A., T.S., and Y.K. acknowledge support by Grants-in Aid for Scientific Research from the Ministry of Education, Culture, Sports, Sciences, and Technology (MEXT), Japan. P.N., J. M. F. and A. J. H. also acknowledge COST action BM1005 for providing networking opportunities. NR 100 TC 62 Z9 65 U1 11 U2 53 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0891-5849 EI 1873-4596 J9 FREE RADICAL BIO MED JI Free Radic. Biol. Med. PD DEC PY 2014 VL 77 BP 82 EP 94 DI 10.1016/j.freeradbiomed.2014.09.007 PG 13 WC Biochemistry & Molecular Biology; Endocrinology & Metabolism SC Biochemistry & Molecular Biology; Endocrinology & Metabolism GA AW6QA UT WOS:000346392500010 PM 25229186 ER PT J AU Yun, JW Son, MJ Abdelmegeed, MA Banerjee, A Morgan, TR Yoo, SH Song, BJ AF Yun, Jun-Won Son, Min-Jeong Abdelmegeed, Mohamed A. Banerjee, Atrayee Morgan, Timothy R. Yoo, Seong-Ho Song, Byoung-Joon TI Binge alcohol promotes hypoxic liver injury through a CYP2E1-HIF-1 alpha-dependent apoptosis pathway in mice and humans SO FREE RADICAL BIOLOGY AND MEDICINE LA English DT Article DE Binge ethanol; Alcohol-metabolizing enzymes; CYP2E1; Hypoxia; Protein nitration; Apoptosis; Human liver injury; Free radicals ID INDUCIBLE FACTOR 1-ALPHA; INDUCED MITOCHONDRIAL DYSFUNCTION; PROLYL HYDROXYLASE-ACTIVITY; PROTEIN-TYROSINE NITRATION; NITRIC-OXIDE SYNTHASE; FATTY LIVER; PROTEASOME ACTIVITY; OXYGEN-CONSUMPTION; CYTOCHROME P4502E1; ETHANOL AB Binge drinking, a common pattern of alcohol ingestion, is known to potentiate liver injury caused by chronic alcohol abuse. This study was aimed at investigating the effects of acute binge alcohol on hypoxia-inducible factor-la (HIF-1 alpha)-mediated liver injury and the roles of alcohol-metabolizing enzymes in alcohol-induced hypoxia and hepatotoxicity. Mice and human specimens assigned to binge or nonbinge groups were analyzed for blood alcohol concentration (BAC), alcohol-metabolizing enzymes, HIF-1 alpha-related protein nitration, and apoptosis. Binge alcohol promoted acute liver injury in mice with elevated levels of ethanol-inducible cytochrome P450 2E1 (CYP2E1) and hypoxia, both of which were colocalized in the centrilobular areas. We observed positive correlations among elevated BAC, CYP2E1, and HIF-1 alpha in mice and humans exposed to binge alcohol. The CYP2E1 protein levels (r = 0.629, p = 0.001) and activity (r = 0.641, p = 0.001) showed a significantly positive correlation with BAC in human livers. HIF-1 alpha levels were also positively correlated with BAC (r = 0.745, p < 0.001) or CYP2E1 activity (r = 0.792, p < 0.001) in humans. Binge alcohol promoted protein nitration and apoptosis with significant correlations observed between inducible nitric oxide synthase and BAC, CYP2E1, or HIF-1 alpha in human specimens. Binge-alcohol-induced HIF-1 alpha activation and subsequent protein nitration or apoptosis seen in wild type were significantly alleviated in the corresponding Cyp2e1-null mice, whereas pretreatment with an HIF-1 alpha inhibitor, PX-478, prevented HIF-1 alpha elevation with a trend of decreased levels of 3-nitrotyrosine and apoptosis, supporting the roles of CYP2E1 and HIF-1 alpha in binge-alcohol-mediated protein nitration and hepatotoxicity. Thus binge alcohol promotes acute liver injury in mice and humans at least partly through a CYP2E1-HIF-1 alpha-dependent apoptosis pathway. Published by Elsevier Inc. C1 [Yun, Jun-Won; Abdelmegeed, Mohamed A.; Banerjee, Atrayee; Song, Byoung-Joon] NIAAA, Lab Membrane Biochem & Biophys, Bethesda, MD 20892 USA. [Son, Min-Jeong; Yoo, Seong-Ho] Seoul Natl Univ, Coll Med, Inst Forens Med, Seoul, South Korea. [Morgan, Timothy R.] Vet Adm Long Beach Healthcare Syst, Gastroenterol Serv, Long Beach, CA 90822 USA. [Morgan, Timothy R.] Univ Calif Irvine, Div Gastroenterol, Irvine, CA 92697 USA. RP Yoo, SH (reprint author), Seoul Natl Univ, Coll Med, Inst Forens Med, Seoul, South Korea. EM yoosh@snu.ac.kr; bj.song@nih.gov FU Intramural Program of the National Institute on Alcohol Abuse and Alcoholism; National Research Foundation grant - Korean government [800-20120365] FX This research was supported by the Intramural Program of the National Institute on Alcohol Abuse and Alcoholism and a National Research Foundation grant funded by the Korean government (800-20120365 to S.-H.Y.). We are also grateful to Dr. Klaus Gawrisch for his support. NR 55 TC 7 Z9 8 U1 4 U2 14 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0891-5849 EI 1873-4596 J9 FREE RADICAL BIO MED JI Free Radic. Biol. Med. PD DEC PY 2014 VL 77 BP 183 EP 194 DI 10.1016/j.freeradbiomed.2014.08.030 PG 12 WC Biochemistry & Molecular Biology; Endocrinology & Metabolism SC Biochemistry & Molecular Biology; Endocrinology & Metabolism GA AW6QA UT WOS:000346392500018 PM 25236742 ER PT J AU Allen, AK Nesmith, JE Golden, A AF Allen, Anna K. Nesmith, Jessica E. Golden, Andy TI An RNAi-Based Suppressor Screen Identifies Interactors of the Myt1 Ortholog of Caenorhabditis elegans SO G3-GENES GENOMES GENETICS LA English DT Article DE WEE-1.3; fertility; suppressor; oocyte maturation; EGA ID TO-EMBRYO TRANSITION; OOCYTE MEIOTIC MATURATION; YEAST NUCLEOLAR PROTEIN; CELL-CYCLE PROGRESSION; LARGE GENE LISTS; C-ELEGANS; ENDOPLASMIC-RETICULUM; FUNCTIONAL-ANALYSIS; HISTONE H3; KINASE AB Oocyte maturation in all species is controlled by a protein complex termed the maturation promoting factor (MPF). MPF comprises a cyclin-dependent kinase (CDK) and its partner cyclin, and it is regulated by dueling regulatory phosphorylation events on the CDK. In Caenorhabditis elegans, the Wee1/Myt1 ortholog WEE-1.3 provides the inhibitory phosphorylations on CDK-1 that keep MPF inactive and halt meiosis. Prior work has shown that depletion of WEE-1.3 in C. elegans results in precocious oocyte maturation in vivo and a highly penetrant infertility phenotype. This study sought to further define the precocious maturation phenotype and to identify novel interactors with WEE-1.3. We found that WEE-1.3 is expressed throughout the germline and in developing embryos in a perinuclear pattern, and demonstrated that oocytes in WEE-1.3-depleted germlines have begun to transcribe embryonic genes and exhibit inappropriate expression of proteins normally restricted to fertilized eggs. In addition, we performed an RNAi suppressor screen of the infertile phenotype to identify novel factors that, when co-depleted with WEE-1.3, restore fertility to these animals. We screened similar to 1900 essential genes by RNAi feeding and identified 44 (similar to 2% of the tested genes) that are suppressors of the WEE-1.3 depletion phenotype. The suppressors include many previously unidentified players in the meiotic cell cycle and represent a pool of potential WEE-1.3 interacting proteins that function during C. elegans oocyte maturation and zygotic development. C1 [Allen, Anna K.; Nesmith, Jessica E.; Golden, Andy] NIDDK, Lab Biochem & Genet, NIH, Bethesda, MD 20892 USA. RP Allen, AK (reprint author), Howard Univ, EE Just Hall,Room 244, Washington, DC 20059 USA. EM anna.allen@howard.edu FU Intramural Research Program of the NIH, The National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK); NIH National Center for Research Resources FX We thank Daphna Joseph-Strauss and Orna Cohen-Fix for generating the EMB RNAi library from the OpenBiosystems RNAi library, David Levine for making the CBD-1::mCherry transgenic animal, John Hanover for help with the DAVID analysis, and Aimee Jaramillo-Lambert, Michelle Bond, and Harold Smith for advice and comments regarding the manuscript. We thank members of the O'Connell and Golden laboratory for valuable discussions. This research was supported by the Intramural Research Program of the NIH, The National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK). Some nematode strains used in this work were provided by the Caenorhabditis Genetics Center, which is funded by the NIH National Center for Research Resources. NR 64 TC 2 Z9 2 U1 2 U2 6 PU GENETICS SOCIETY AMERICA PI BETHESDA PA 9650 ROCKVILLE AVE, BETHESDA, MD 20814 USA SN 2160-1836 J9 G3-GENES GENOM GENET JI G3-Genes Genomes Genet. PD DEC 1 PY 2014 VL 4 IS 12 BP 2329 EP 2343 DI 10.1534/g3.114.013649 PG 15 WC Genetics & Heredity SC Genetics & Heredity GA AW5WJ UT WOS:000346341500004 PM 25298536 ER PT J AU Jansen, M Scholvinck, DW Kushima, R Sekine, S Weusten, BLAM Wang, GQQ Fleischer, DE Yoshinaga, S Dawsey, SM Meijer, SL Bergman, JJGHM Oda, I AF Jansen, Marnix Scholvinck, Dirk W. Kushima, Ryoji Sekine, Shigeki Weusten, Bas L. A. M. Wang, Guiqi Q. Fleischer, David E. Yoshinaga, Shigetaka Dawsey, Sanford M. Meijer, Sybren L. Bergman, Jacques J. G. H. M. Oda, Ichiro TI Is it justified to ablate flat-type esophageal squamous cancer? An analysis of endoscopic submucosal dissection specimens of lesions meeting the selection criteria of radio frequency studies SO GASTROINTESTINAL ENDOSCOPY LA English DT Article ID CELL CARCINOMA; RADIOFREQUENCY ABLATION; MUCOSAL RESECTION; METASTASIS; PREVALENCE; EPITHELIUM; NEOPLASIA; DEVICE AB Background: Endoscopic radiofrequency ablation (RFA) appears to be a safe and effective treatment for flat-type noninvasive squamous neoplasia of the esophagus. However, if RFA is applied to lesions containing invasive cancer (esophageal squamous cell carcinoma [ESCC]), histological features associated with lymph node metastases may remain undetected. In addition, extension of neoplasia down the ducts of esophageal submucosal glands (SMGs) may create a sheltered "niche" beyond the reach of ablation. Objective: To determine the RFA eligibility of flat-type ESCC. Design: Retrospective analysis of prospectively collected data of ESCC patients. Setting: National Cancer Center Hospital, Tokyo, Japan. Patients: Patients with flat-type ESCC larger than 3 cm removed by endoscopic submucosal dissection (ESD). Interventions: Three endoscopists involved in RFA studies in China reviewed endoscopic images to select lesions eligible for RFA. Corresponding ESD resection specimens were histologically examined. Main Outcome Measurements: The presence of poor histological features (ie, invasion in m3 or deeper, poor tumor differentiation, or lymphovascular invasion) and the number of involved esophageal SMGs and ducts. Results: Sixty-five lesions were included, 17 (26%) of which qualified as RFA eligible by RFA endoscopists. Interobserver agreement for this assessment was poor (k = 0.09). Six of the 17 specimens (35%) showed relevant disease: 4 lesions invaded in the muscularis mucosae, 1 of which also showed lymphovascular invasion; 2 lesions showed extension of neoplasia into SMGs. Limitations: Limited number of cases. RFA eligibility status was based on analysis of still images. Conclusions: One third of flat-type ESCC, deemed eligible for RFA, demonstrated histological features that are considered (relative) contraindications to endoscopic treatment. Because it appears difficult for endoscopists to identify low-risk ESCC, conservative use of RFA for flat-type ESCC is advocated until long-term follow-up data are available. C1 [Jansen, Marnix; Meijer, Sybren L.] Univ Amsterdam, Acad Med Ctr, Dept Pathol, NL-1105 AZ Amsterdam, Netherlands. [Scholvinck, Dirk W.; Bergman, Jacques J. G. H. M.] Univ Amsterdam, Acad Med Ctr, Dept Gastroenterol & Hepatol, NL-1105 AZ Amsterdam, Netherlands. [Scholvinck, Dirk W.; Weusten, Bas L. A. M.] St Antonius Hosp, Dept Gastroenterol & Hepatol, Nieuwegein, Netherlands. [Kushima, Ryoji; Sekine, Shigeki] Natl Canc Ctr, Div Pathol, Tokyo, Japan. [Yoshinaga, Shigetaka; Oda, Ichiro] Natl Canc Ctr, Endoscopy Div, Tokyo, Japan. [Wang, Guiqi Q.] Chinese Acad Med Sci, Peking Union Med Coll, Dept Endoscopy, Canc Inst & Hosp, Beijing 100730, Peoples R China. [Fleischer, David E.] Mayo Clin, Dept Gastroenterol & Hepatol, Scottsdale, AZ USA. [Dawsey, Sanford M.] NCI, Div Canc Epidemiol & Genet, NIH, Bethesda, MD 20892 USA. RP Bergman, JJGHM (reprint author), Univ Amsterdam, Acad Med Ctr, Dept Gastroenterol & Hepatol, Meibergdreef 9, NL-1105 AZ Amsterdam, Netherlands. NR 24 TC 3 Z9 3 U1 0 U2 2 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0016-5107 EI 1097-6779 J9 GASTROINTEST ENDOSC JI Gastrointest. Endosc. PD DEC PY 2014 VL 80 IS 6 BP 995 EP 1002 DI 10.1016/j.gie.2014.09.004 PG 8 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA AW7JY UT WOS:000346441600009 PM 25434658 ER PT J AU Ma, BY Kolb, S Diprima, M Karna, M Tosato, G Yang, QQ Huang, Q Nussinov, R AF Ma, Buyong Kolb, Stephanie Diprima, Michael Karna, Molleshree Tosato, Giovanna Yang, Qiqi Huang, Qiang Nussinov, Ruth TI Investigation of the interactions between the EphB2 receptor and SNEW peptide variants SO GROWTH FACTORS LA English DT Article DE EphB2 receptor; ephrin ligands; inhibitor design; molecular dynamics simulations; protein stability; protein dynamics ID MOLECULAR-DYNAMICS; EPHA4 RECEPTOR; TUMOR SUPPRESSION; PROTEIN DYNAMICS; CELL; EPHRINS; BINDING; CANCER; PROLIFERATION; SIMULATION AB EphB2 interacts with cell surface-bound ephrin ligands to relay bidirectional signals. Overexpression of the EphB2 receptor protein has been linked to different types of cancer. The SNEW (SNEWIQPRLPQH) peptide binds with high selectivity and moderate affinity to EphB2, inhibiting Eph-ephrin interactions by competing with ephrin ligands for the EphB2 high-affinity pocket. We used rigorous free energy perturbation (FEP) calculations to re-evaluate the binding interactions of SNEW peptide with the EphB2 receptor, followed by experimental testing of the computational results. Our results provide insight into dynamic interactions of EphB2 with SNEW peptide. While the first four residues of the SNEW peptide are already highly optimized, change of the C-terminal end of the peptide has the potential to improve SNEW-binding affinity. We identified a PXSPY motif that can be similarly aligned with several other EphB2-binding peptides. C1 [Ma, Buyong; Kolb, Stephanie; Nussinov, Ruth] NCI, Basic Sci Program, Leidos Biomed Res Inc, Canc & Inflammat Program, Frederick, MD 21702 USA. [Diprima, Michael; Karna, Molleshree; Tosato, Giovanna] NCI, Cellular Oncol Lab, Ctr Canc Res, Bethesda, MD 20892 USA. [Yang, Qiqi; Huang, Qiang] Fudan Univ, Sch Life Sci, State Key Lab Genet Engn, Shanghai 200433, Peoples R China. [Nussinov, Ruth] Tel Aviv Univ, Sackler Sch Med, Sackler Inst Mol Med, Dept Human Genet & Mol Med, IL-69978 Tel Aviv, Israel. RP Ma, BY (reprint author), NCI, Basic Sci Program, Leidos Biomed Res Inc, Canc & Inflammat Program, Frederick, MD 21702 USA. EM mabuyong@-mail.nih.gov; NussinoR@helix.nih.gov RI Ma, Buyong/F-9491-2011 OI Ma, Buyong/0000-0002-7383-719X FU National Cancer Institute, National Institutes of Health [HHSN261200800001E]; CCR/NCI; NIBIB/NIH Biomedical Engineering Summer Internship Program (BESIP); Hi-tech Research and Development Program of China [2008AA02Z311]; Shanghai Natural Science Foundation [13ZR1402400]; Shanghai Leading Academic Discipline Project [B111] FX The authors report no declarations of interest. This project has been funded in whole or in part with federal funds from the National Cancer Institute, National Institutes of Health, under Contract number HHSN261200800001E. This work was also supported by the intramural program of the CCR/NCI. M. K. was supported by the NIBIB/NIH Biomedical Engineering Summer Internship Program (BESIP). Q. Huang was supported in part by the grants from the Hi-tech Research and Development Program of China (No. 2008AA02Z311), the Shanghai Natural Science Foundation (No. 13ZR1402400), and the Shanghai Leading Academic Discipline Project (B111). NR 53 TC 3 Z9 3 U1 1 U2 5 PU INFORMA HEALTHCARE PI LONDON PA TELEPHONE HOUSE, 69-77 PAUL STREET, LONDON EC2A 4LQ, ENGLAND SN 0897-7194 EI 1029-2292 J9 GROWTH FACTORS JI Growth Factors PD DEC PY 2014 VL 32 IS 6 BP 236 EP 246 DI 10.3109/08977194.2014.985786 PG 11 WC Cell Biology; Endocrinology & Metabolism SC Cell Biology; Endocrinology & Metabolism GA AW5FZ UT WOS:000346302600009 PM 25410963 ER PT J AU Maroun, MC Olivero, O Lipovich, L Stark, A Tait, L Bandyopadhyay, S Burke, M Zarbo, R Chitale, D Nathanson, SD Long, M Peebles, C Madrid, FF AF Maroun, Marie-Claire Olivero, Ofelia Lipovich, Leonard Stark, Azadeh Tait, Larry Bandyopadhyay, Sudeshna Burke, Matthew Zarbo, Richard Chitale, Dhananjay Nathanson, S. David Long, Mike Peebles, Carol Madrid, Felix Fernandez TI Anti-centrosome antibodies in breast cancer are the expression of autoimmunity SO IMMUNOLOGIC RESEARCH LA English DT Article DE Breast cancer; Centrosome proteins; Autoimmunity; Chromosomal instability ID UBIQUITIN-PROTEASOME PATHWAY; DUCTAL CARCINOMA; STATHMIN; AUTOANTIBODIES; KINASE; TUMORS; ACTIN; ONCOPROTEIN-18; OVEREXPRESSION; INSTABILITY AB Centrosome abnormalities have been observed in nearly all human solid tumors, but their role in tumorigenesis is unclear. We have demonstrated that autoantibodies reacting with antigens in centrosomes are frequently found in BC sera. In this work, we attempted to characterize the centrosome antigens associated with BC. We immunoscreened a T7 cDNA library of BC proteins with BC sera, and the autoantigens identified were printed as a microarray and hybridized with BC and control sera. We used immunohistochemistry (IHC) to investigate the expression of the cloned autoantigens in BC tissue. Immunoscreening with BC sera led to the cloning of autoantibodies recognizing epitopes developing in a family of proteins located on centrosomes such as peri-centriolar material-1, isomorph CRA, stathmin1, HS actin gamma1, SUMO/sentrin peptidase 2, and ubiquitin-conjugating enzyme E2 variant 1. Antibody reactivity to these proteins that are associated with centrosome assembly and/or microtubule function was highly associated with the diagnosis of BC. IHC staining of formalin-fixed paraffin-embedded sections with specific antibodies showed that aurora and stathmin are expressed in BC. The discovery of autoantibodies to important centrosome antigens associated with BC suggests that this immune reactivity could be related to autoimmunity developing in BC. Our finding that some of these antibodies are also present in a group of healthy women suggests that breakdown of tolerance to centrosome proteins may occur early in breast carcinogenesis and that autoantibodies to centrosome antigens might be biomarkers of early BC. C1 [Maroun, Marie-Claire; Madrid, Felix Fernandez] Wayne State Univ, Sch Med, Dept Internal Med, Div Rheumatol, Detroit, MI 48201 USA. [Olivero, Ofelia] NCI, Lab Canc Biol & Genet, NIH, Bethesda, MD 20892 USA. [Lipovich, Leonard; Madrid, Felix Fernandez] Wayne State Univ, Ctr Mol Med & Genet, Detroit, MI 48201 USA. [Stark, Azadeh] Henry Ford Hlth Syst, Dept Pathol, Detroit, MI 48202 USA. [Tait, Larry; Madrid, Felix Fernandez] Karmanos Canc Inst, Detroit, MI 48201 USA. [Bandyopadhyay, Sudeshna] Wayne State Univ, Dept Pathol, Detroit, MI 48202 USA. [Burke, Matthew] Henry Ford Hosp & Hlth Network, Dept Diagnost Radiol, Detroit, MI 48202 USA. [Zarbo, Richard; Chitale, Dhananjay] Henry Ford Hosp, Detroit, MI 48202 USA. [Nathanson, S. David] Henry Ford Hlth Syst, Dept Surg, Detroit, MI 48202 USA. [Long, Mike] Childrens Hosp Michigan, Wayne State Sch Med, Dept Pathol, Detroit, MI USA. [Peebles, Carol] INOVA Diagnost Inc, San Diego, CA 92131 USA. RP Maroun, MC (reprint author), Wayne State Univ, Sch Med, Dept Internal Med, Div Rheumatol, 540 Canfield, Detroit, MI 48201 USA. EM mmaroun@med.wayne.edu FU NIH NCI [R01 122277] FX This work was done with the partial support of NIH NCI R01 122277. We thank the technical work of Naimei Tang and Xinbo Zhang in several aspects of this project. NR 57 TC 3 Z9 3 U1 0 U2 3 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DRIVE SUITE 208, TOTOWA, NJ 07512 USA SN 0257-277X EI 1559-0755 J9 IMMUNOL RES JI Immunol. Res. PD DEC PY 2014 VL 60 IS 2-3 SI SI BP 339 EP 347 DI 10.1007/s12026-014-8582-4 PG 9 WC Immunology SC Immunology GA AW6YT UT WOS:000346412300022 PM 25420961 ER PT J AU Courcoulas, AP Yanovski, SZ Bonds, D Eggerman, TL Horlick, M Staten, MA Arterburn, DE AF Courcoulas, Anita P. Yanovski, Susan Z. Bonds, Denise Eggerman, Thomas L. Horlick, Mary Staten, Myrlene A. Arterburn, David E. TI Long-term Outcomes of Bariatric Surgery A National Institutes of Health Symposium SO JAMA SURGERY LA English DT Article ID SWEDISH OBESE SUBJECTS; GASTRIC BYPASS-SURGERY; HIGH-RISK PATIENTS; CONTROLLED INTERVENTION; LONGITUDINAL ASSESSMENT; CARDIOVASCULAR EVENTS; SLEEVE GASTRECTOMY; MEDICAL THERAPY; TRIAL; ATTITUDES AB IMPORTANCE The clinical evidence base demonstrating bariatric surgery's health benefits is much larger than it was when the National Institutes of Health last held a consensus panel in 1991. Still, it remains unclear whether ongoing studies will address critical questions about long-term complication rates and the sustainability of weight loss and comorbidity control. OBJECTIVE To summarize findings from a multidisciplinary workshop convened in May 2013 by the National Institute of Diabetes and Digestive and Kidney Diseases and the National Heart, Lung, and Blood Institute. The workshop aimed to summarize the current state of knowledge of bariatric surgery, review research findings on the long-term outcomes of bariatric surgery, and establish priorities for future research directions. EVIDENCE REVIEW The evidence presented at the workshop was selected by the planning committee for both its quality and duration of follow-up. The data review emphasized randomized clinical trials and large observational studies with long-term follow-up, with or without a control group. FINDINGS Several small randomized clinical trials showed greater weight loss and type 2 diabetes mellitus remission compared with nonsurgical treatments within the first 2 years of follow-up after bariatric surgery. Large, long-term observational studies have shown durable (>5 years) weight loss, diabetes, and lipid improvements with bariatric surgery. Still unclear are predictors of outcomes, long-term complications, long-term survival, microvascular and macrovascular events, mental health outcomes, and costs. The studies needed to address these knowledge gaps would be expensive and logistically difficult to perform. CONCLUSIONS AND RELEVANCE High-quality evidence shows that bariatric surgical procedures result in greater weight loss than nonsurgical treatments and are more effective at inducing initial type 2 diabetes mellitus remission in obese patients. More information is needed about the long-term durability of comorbidity control and complications after bariatric procedures and this evidence will most likely come from carefully designed observational studies. C1 [Courcoulas, Anita P.] Univ Pittsburgh, Med Ctr, Pittsburgh, PA 15213 USA. [Yanovski, Susan Z.; Horlick, Mary] NIDDK, Div Digest Dis & Nutr, NIH, Bethesda, MD 20892 USA. [Bonds, Denise] NHLBI, Div Cardiovasc Sci, NIH, Bethesda, MD 20892 USA. [Eggerman, Thomas L.; Staten, Myrlene A.] NIDDK, Div Diabet, NIH, Bethesda, MD 20892 USA. [Arterburn, David E.] Grp Hlth Cooperat Puget Sound, Grp Hlth Res Inst, Seattle, WA USA. RP Courcoulas, AP (reprint author), Univ Pittsburgh, Med Ctr, 3380 Blvd Allies,Ste 390, Pittsburgh, PA 15213 USA. EM courcoulasap@upmc.edu FU National Institutes of Health (NIH)-National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK); Covidien; EndoGastric Solutions; Nutrisystem; J&J Ethicon Scientific; NIH; Informed Medical Decisions Foundation; Department of Veterans Affairs; Agency for Healthcare Research and Quality FX Dr Courcoulas has received grants from the National Institutes of Health (NIH)-National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK), Covidien, EndoGastric Solutions, and Nutrisystem, and advisory board and personal fees from J&J Ethicon Scientific outside of the submitted work. Dr Arterburn has received grants from the NIH, grants and nonfinancial support from the Informed Medical Decisions Foundation, grants from the Department of Veterans Affairs, and grants from the Agency for Healthcare Research and Quality outside of the submitted work. No other disclosures were reported. NR 47 TC 46 Z9 46 U1 2 U2 13 PU AMER MEDICAL ASSOC PI CHICAGO PA 330 N WABASH AVE, STE 39300, CHICAGO, IL 60611-5885 USA SN 2168-6254 EI 2168-6262 J9 JAMA SURG JI JAMA Surg. PD DEC PY 2014 VL 149 IS 12 BP 1323 EP 1329 DI 10.1001/jamasurg.2014.2440 PG 7 WC Surgery SC Surgery GA AW7YK UT WOS:000346477400025 PM 25271405 ER PT J AU Thorpe, RJ McCleary, R Smolen, JR Whitfield, KE Simonsick, EM LaVeist, T AF Thorpe, Roland J., Jr. McCleary, Rachael Smolen, Jenny R. Whitfield, Keith E. Simonsick, Eleanor M. LaVeist, Thomas TI Racial Disparities in Disability Among Older Adults: Finding From the Exploring Health Disparities in Integrated Communities Study SO JOURNAL OF AGING AND HEALTH LA English DT Article DE disability; older adults; racial disparities; African Americans; EHDIC ID INCIDENT MOBILITY LIMITATION; LOWER-EXTREMITY FUNCTION; BLACK-WHITE DIFFERENCES; SOCIOECONOMIC-STATUS; RESIDENTIAL SEGREGATION; RACE DISPARITIES; NEIGHBORHOOD CHARACTERISTICS; AFRICAN-AMERICANS; PHYSICAL FUNCTION; SOCIAL-CONTEXT AB Objective: Persistent and consistently observed racial disparities in physical functioning likely stem from racial differences in social resources and environmental conditions. Method: We examined the association between race and reported difficulty performing instrumental activities of daily living (IADL) in 347 African American (45.5%) and Whites aged 50 or above in the Exploring Health Disparities in Integrated Communities-Southwest Baltimore, Maryland Study (EHDIC-SWB). Results: Contrary to previous studies, African Americans had lower rates of disability (women: 25.6% vs. 44.6%, p = .006; men: 15.7% vs. 32.9%; p = .017) than Whites. After adjusting for sociodemographics, health behaviors, and comorbidities, African American women (odds ratio [OR] = 0.32, 95% confidence interval [CI] = [0.14, 0.70]) and African American men (OR = 0.34, 95% CI = [0.13, 0.90]) retained their functional advantage compared with White women and men, respectively. Conclusion: These findings within an integrated, low-income urban sample support efforts to ameliorate health disparities by focusing on the social context in which people live. C1 [Thorpe, Roland J., Jr.; McCleary, Rachael; Smolen, Jenny R.; LaVeist, Thomas] Johns Hopkins Bloomberg Sch Publ Hlth, Hopkins Ctr Hlth Dispar Solut, Baltimore, MD 21205 USA. [Thorpe, Roland J., Jr.; Whitfield, Keith E.] Duke Univ, Ctr Biobehav Hlth Dispar Res, Durham, NC USA. [Simonsick, Eleanor M.] Johns Hopkins Sch Med, Baltimore, MD USA. [Simonsick, Eleanor M.] NIA, Baltimore, MD 21224 USA. RP Thorpe, RJ (reprint author), Johns Hopkins Bloomberg Sch Publ Hlth, Hopkins Ctr Hlth Dispar Solut, 624 N Broadway,Ste 708, Baltimore, MD 21205 USA. EM rthorpe@jhu.edu FU NIMHD NIH HHS [P60MD000214, P60 MD000217, P60 MD000214] NR 73 TC 2 Z9 2 U1 2 U2 13 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 0898-2643 EI 1552-6887 J9 J AGING HEALTH JI J. Aging Health PD DEC PY 2014 VL 26 IS 8 SI SI BP 1261 EP 1279 DI 10.1177/0898264314534892 PG 19 WC Gerontology; Health Policy & Services SC Geriatrics & Gerontology; Health Care Sciences & Services GA AW4PD UT WOS:000346262200002 PM 25502241 ER PT J AU Yeboah, J Bluemke, DA Hundley, WG Rodriguez, CJ Lima, JAC Herrington, DM AF Yeboah, Joseph Bluemke, David A. Hundley, W. Gregory Rodriguez, Carlos J. Lima, Joao A. C. Herrington, David M. TI Left Ventricular Dilation and Incident Congestive Heart Failure in Asymptomatic Adults Without Cardiovascular Disease: Multi-Ethnic Study of Atherosclerosis (MESA) SO JOURNAL OF CARDIAC FAILURE LA English DT Article DE Left ventricular dilation; left ventricular remodeling; heart failure; risk factors; left ventricular ejection fraction ID MYOCARDIAL-INFARCTION; SYSTOLIC DYSFUNCTION; MORTALITY; SURVIVAL AB Background: Limited data exist on the association between left ventricular (LV) dilation/remodeling and incident heart failure (I-IF), especially in adults without prior myocardial infarction (MI) and valvular heart disease. We assessed the association between LV dilation and remodeling and incident HF in a multiethnic cohort. Methods and Results: A total of 4,974 of 6,814 participants in the Multi-Ethnic Study of Atherosclerosis (MESA) had cardiac magnetic resonance imaging and complete data. Kaplan-Meier and Cox proportional hazard analyses were used to assess the association between LV end-diastolic diameter (LVEDD) and adjudicated HF. During the 12 years of follow-up (mean 9.4 y), 177 (3.6%) HF events occurred, 126(71.2%) in HF with reduced ejection fraction (EF) and 51(28.8%) in HF with preserved EF. LV dilation (LVEDD >52 mm or > 95th percentile) was associated with HF in univariate (hazard ratio [HR] 1.21, 95% confidence interval [CI] 1.08-1.46; P = .007) and multivariable Cox models (HR 1.28, 95% CI 1.09-1.57; P = .01) adjusting for traditional risk factors, medication use, LV EF, and interim MI. We found a significant multiplicative interaction between LVEDD and LV EF in our full multivariable models. Participants with dilated LV and preserved EF had increased risk [HR 2.22, 95% CI 1.46-3.37; P = .006) and those with dilated LV and reduced EF had worse prognosis (HR 7.35, 95% CI 2.36-22.85; P = .0006) compared with normal-size LV and preserved EF. A high proportion of participants with LV dilation had eccentric remodeling, a risk factor for HF. Concentric hypertrophy, also a risk factor for HF, was common in the normal-size LV group. Conclusions: LV dilation predicts incident HF independently from risk factors, LV EF, and interim MI. C1 [Yeboah, Joseph; Hundley, W. Gregory; Rodriguez, Carlos J.; Herrington, David M.] Wake Forest Univ, Bowman Gray Sch Med, Dept Internal Med, Winston Salem, NC 27103 USA. [Yeboah, Joseph; Hundley, W. Gregory; Rodriguez, Carlos J.; Herrington, David M.] Wake Forest Univ, Bowman Gray Sch Med, Dept Cardiol, Winston Salem, NC USA. [Yeboah, Joseph; Rodriguez, Carlos J.; Herrington, David M.] Wake Forest Sch Med, Dept Epidemiol & Prevent, Winston Salem, NC 27157 USA. [Bluemke, David A.] NIH, Ctr Clin, Bethesda, MD 20892 USA. [Lima, Joao A. C.] Johns Hopkins Univ, Baltimore, MD USA. RP Yeboah, J (reprint author), Wake Forest Sch Med, Dept Internal Med Cardiol, Med Ctr Blvd, Winston Salem, NC 27157 USA. EM jyeboah@wakehealth.edu OI Bluemke, David/0000-0002-8323-8086 FU NIH/NHLBI [N01-HC-95159, N01-HC-95160, N01-HC-95161, N01-HC-95162, N01-HC-95163, N01-HC-95164, N01-HC-95165, N01-HC-95166, N01-HC-95167]; [R01HL098445] FX NIH/NHLBI contracts N01-HC-95159 through N01-HC-95167 and a Diversity Supplement to R01HL098445. NR 20 TC 3 Z9 3 U1 0 U2 1 PU CHURCHILL LIVINGSTONE INC MEDICAL PUBLISHERS PI PHILADELPHIA PA CURTIS CENTER, INDEPENDENCE SQUARE WEST, PHILADELPHIA, PA 19106-3399 USA SN 1071-9164 EI 1532-8414 J9 J CARD FAIL JI J. Card. Fail. PD DEC PY 2014 VL 20 IS 12 BP 905 EP 911 DI 10.1016/j.cardfail.2014.09.002 PG 7 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA AW4CP UT WOS:000346229300006 PM 25225112 ER PT J AU Murthy, SB Moradiya, Y Shah, S Naval, NS AF Murthy, Santosh B. Moradiya, Yogesh Shah, Shreyansh Naval, Neeraj S. TI In-hospital outcomes of aneurysmal subarachnoid hemorrhage associated with cocaine use in the USA SO JOURNAL OF CLINICAL NEUROSCIENCE LA English DT Article DE Cocaine use; Intracranial aneurysms; Nationwide Inpatient Sample; Subarachnoid hemorrhage ID VASOSPASM; ABUSE AB Cocaine use is associated with higher mortality in small retrospective studies of brain-injured patients. We aimed to explore in-hospital outcomes in a large population based study of aneurysmal subarachnoid hemorrhage (aSAH) with cocaine use. aSAH patients were identified from the 2007-2010 USA Nationwide Inpatient Sample using International Classification of Disease, Ninth Revision codes. Demographics, comorbidities and surgical procedures were compared between cocaine users and non-users. The primary outcomes were in-hospital mortality and home discharge/self-care. Secondary outcomes were vasospasm treated with angioplasty, hydrocephalus, gastrostomy and tracheostomy. There were 103,876 patients with aSAH. The cocaine group were younger (45.8 +/- 9.8 versus 58.4 +/- 15.8, p < 0.001), predominantly male (53.3% versus 38.5%, p < 0.001) and had a higher proportion of black patients (36.9% versus 11.5%, p < 0.001). The incidence of seizures was higher among cocaine users (16.2% versus 11.1%, p < 0.001). Endovascular coiling of intracranial aneurysms (24% versus 18.5%, p < 0.001) was more frequent in cocaine users. The univariate analysis showed higher rates of in-hospital mortality and vasospasm treated with angioplasty, but lower home discharge in the cocaine group. In the multivariate analysis, the cocaine cohort had higher in-hospital mortality (odds ratio [OR] 1.43, 95% confidence interval [CI] 1.27-1.61, p < 0.001) and lower home discharge rates (OR 0.79, 95% CI 0.69-0.87, p < 0.001) after adjusting for confounders. Rates of vasospasm treated with angioplasty however were similar between the two groups. Cocaine use was found to be independently associated with poor outcomes, particularly higher mortality and lower home discharge rates. Cocaine use however, was not associated with vasospasm that required treatment with angioplasty. Prospective confirmation is warranted. (C) 2014 Elsevier Ltd. All rights reserved. C1 [Murthy, Santosh B.; Moradiya, Yogesh; Naval, Neeraj S.] Johns Hopkins Univ, Sch Med, Div Neurosci Crit Care, Baltimore, MD 21287 USA. [Shah, Shreyansh] NIH, Dept Vasc Neurol, Bethesda, MD 20892 USA. RP Murthy, SB (reprint author), Johns Hopkins Univ, Sch Med, Div Neurosci Crit Care, 600 N Wolfe St,Phipps 455, Baltimore, MD 21287 USA. EM santoshbmurthy@gmail.com NR 18 TC 6 Z9 6 U1 0 U2 1 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0967-5868 EI 1532-2653 J9 J CLIN NEUROSCI JI J. Clin. Neurosci. PD DEC PY 2014 VL 21 IS 12 BP 2088 EP 2091 DI 10.1016/j.jocn.2014.05.012 PG 4 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA AX0DF UT WOS:000346622900006 PM 24998859 ER PT J AU Kim, S Yang, JY Jung, ES Lee, J Heo, NJ Lee, JW Na, KY Han, JS AF Kim, Sejoong Yang, Jin Young Jung, Eun Sook Lee, Jeonghwan Heo, Nam Ju Lee, Jae Wook Na, Ki Young Han, Jin Suk TI Effects of Sodium Citrate on Salt Sensitivity and Kidney Injury in Chronic Renal Failure SO JOURNAL OF KOREAN MEDICAL SCIENCE LA English DT Article DE Kidney Failure, Chronic; Citrates; Acidosis; Natriuresis ID GLOMERULAR-FILTRATION-RATE; METABOLIC-ACIDOSIS; ESSENTIAL-HYPERTENSION; ENDOTHELIN; DECLINE; TRANSPORTERS; PROGRESSION; RATS; GFR AB Metabolic acidosis, which is observed in salt-sensitive hypertension, is also associated with kidney injury. Alkali therapy in chronic renal failure (CRF) may ameliorate the progression of kidney disease; however, few studies have examined the effects of alkali therapy on salt sensitivity and kidney injury in CRF. We randomly administered standard diet (SD), sodium chloride with 20% casein diet (NACL), or sodium citrate with 20% casein diet (NACT) to Sprague-Dawley rats after a CRF or a sham operation. Four weeks after 5/6 nephrectomy, serum bicarbonate levels were higher in the NACT-treated group. On the pressure-natriuresis curve, NACT-treated CRF rats were more salt-resistant than NACL-treated CRF rats. Additionally, the NACT-treated CRF group showed less tubulointerstitial damage than the NACL-treated CRF group. The expression and immunoreactivity of NHE3 in the kidney in the NACT-treated CRF group were lower than those in the NACL-treated CRF group. We observed that dietary NACT as alkali therapy in CRF might improve the altered salt-sensitivity and ameliorate the progression of kidney injury compared to the NACL diet, which may be related to reduced renal NHE3 expression. C1 [Kim, Sejoong; Yang, Jin Young; Na, Ki Young] Seoul Natl Univ, Bundang Hosp, Dept Internal Med, Songnam, South Korea. [Kim, Sejoong; Jung, Eun Sook; Heo, Nam Ju; Na, Ki Young; Han, Jin Suk] Seoul Natl Univ, Coll Med, Dept Internal Med, Seoul 151, South Korea. [Lee, Jeonghwan] Hallym Univ, Hangang Sacred Heart Hosp, Dept Internal Med, Seoul, South Korea. [Heo, Nam Ju] Seoul Natl Univ Hosp, Dept Internal Med, Healthcare Syst Gangnam Ctr, Seoul 110744, South Korea. [Lee, Jae Wook] NHLBI, Epithelial Syst Biol Lab, NIH, Bethesda, MD 20892 USA. RP Han, JS (reprint author), Seoul Natl Univ Hosp, Dept Internal Med, 103 Daehak Ro, Seoul 110744, South Korea. EM jshan@snu.ac.kr OI Lee, Jae Wook/0000-0003-0120-8164 FU Seoul National University Bundang Hospital Research Fund [03-2012-020]; National Research Foundation of Korea [2013R1A1A1012689] FX This work was supported by grant from the Seoul National University Bundang Hospital Research Fund (No. 03-2012-020) and grant (No. 2013R1A1A1012689) from the National Research Foundation of Korea. NR 25 TC 1 Z9 2 U1 1 U2 7 PU KOREAN ACAD MEDICAL SCIENCES PI SEOUL PA 302 75 DONG DU ICHON, DONG YONGSAN KU, SEOUL 140 031, SOUTH KOREA SN 1011-8934 EI 1598-6357 J9 J KOREAN MED SCI JI J. Korean Med. Sci. PD DEC PY 2014 VL 29 IS 12 BP 1658 EP 1664 DI 10.3346/jkms.2014.29.12.1658 PG 7 WC Medicine, General & Internal SC General & Internal Medicine GA AW8JF UT WOS:000346507200012 PM 25469066 ER PT J AU Yaniv, Y Lyashkov, AE Sirenko, S Okamoto, Y Guiriba, TR Ziman, BD Morrell, CH Lakatta, EG AF Yaniv, Yael Lyashkov, Alexey E. Sirenko, Syevda Okamoto, Yosuke Guiriba, Toni-Rose Ziman, Bruce D. Morrell, Christopher H. Lakatta, Edward G. TI Stochasticity intrinsic to coupled-clock mechanisms underlies beat-to-beat variability of spontaneous action potential firing in sinoatrial node pacemaker cells SO JOURNAL OF MOLECULAR AND CELLULAR CARDIOLOGY LA English DT Article DE Ca2+ cycling; Ion channels; Physiology; Sarcoplasmic reticulum; Sinoatrial nodal pacemaker cells ID HEART-RATE-VARIABILITY; RECTIFIER K+ CURRENT; CYCLOPIAZONIC ACID; RABBIT SINOATRIAL; IVABRADINE; SYNCHRONIZATION; AUTOMATICITY; MODULATION; KINETICS; CURRENTS AB Recent evidence indicates that the spontaneous action potential (AP) of isolated sinoatrial node cells (SANCs) is regulated by a system of stochastic mechanisms embodied within two clocks: ryanodine receptors of the "Ca2+ clock" within the sarcoplasmic reticulum, spontaneously activate during diastole and discharge local Ca2+ releases (LCRs) beneath the cell surface membrane; clock crosstalk occurs as LCRs activate an inward Na+/Ca2+ exchanger current (I-NCX), which together with I-f and decay of K+ channels prompts the "M clock," the ensemble of sarcolemmal-electrogenic molecules, to generate APs. Prolongation of the average LCR period accompanies prolongation of the average AP beating interval (BI). Moreover, the prolongation of the average AP BI accompanies increased AP BI variability. We hypothesized that both the average AP Bland AP BI variability are dependent upon stochasticity of clock mechanisms reported by the variability of LCR period. We perturbed the coupled-clock system by directly inhibiting the M clock by ivabradine (IVA) or the Ca2+ clock by cyclopiazonic acid (CPA). When either clock is perturbed by IVA (3, 10 and 30 mu M), which has no direct effect on Ca2+ cycling, or CPA (0.5 and 5 mu M), which has no direct effect on the M clock ion channels, the clock system failed to achieve the basal AP Bland both AP BI and AP BI variability increased. The changes in average LCR period and its variability in response to perturbations of the coupled-clock system were correlated with changes in AP beating interval and AP beating interval variability. We conclude that the stochasticity within the coupled-clock system affects and is affected by the AP BI firing rate and rhythm via modulation of the effectiveness of clock coupling. (C) 2014 Elsevier Ltd. All rights reserved. C1 [Yaniv, Yael; Sirenko, Syevda; Okamoto, Yosuke; Guiriba, Toni-Rose; Ziman, Bruce D.; Morrell, Christopher H.; Lakatta, Edward G.] NIA, Lab Cardiovasc Sci, Biomed Res Ctr, Intramural Res Program,NIH, Baltimore, MD 21224 USA. [Yaniv, Yael] Technion Israel Inst Technol, Biomed Engn Fac, Haifa, Israel. [Lyashkov, Alexey E.] NIA, Biomed Res Ctr, Translat Gerontol Branch, Intramural Res Program,NIH, Baltimore, MD 21224 USA. [Morrell, Christopher H.] Loyola Univ, Dept Math & Stat, Baltimore, MD USA. RP Yaniv, Y (reprint author), Technion Israel Inst Technol, Biomed Engn Fac, Haifa, Israel. EM yaely@bm.technion.ac.il; lakattae@grc.nia.nih.gov RI Yaniv, Yael/B-3311-2015 OI Yaniv, Yael/0000-0002-5183-6284 FU National Institute on Aging, National Institutes of Health; Technion V.P.R. Fund -Krbling Biomedical Engineering Research Fund FX The work was supported in part by the Intramural Research Program of the National Institute on Aging, National Institutes of Health and by the Technion V.P.R. Fund -Krbling Biomedical Engineering Research Fund (Y.Y.). NR 34 TC 9 Z9 9 U1 1 U2 15 PU ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD PI LONDON PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND SN 0022-2828 EI 1095-8584 J9 J MOL CELL CARDIOL JI J. Mol. Cell. Cardiol. PD DEC PY 2014 VL 77 BP 1 EP 10 DI 10.1016/j.yjmcc.2014.09.008 PG 10 WC Cardiac & Cardiovascular Systems; Cell Biology SC Cardiovascular System & Cardiology; Cell Biology GA AW7QQ UT WOS:000346460100001 PM 25257916 ER PT J AU Meulendyke, KA Queen, SE Engle, EL Shirk, EN Liu, JY Steiner, JP Nath, A Tarwater, PM Graham, DR Mankowski, JL Zink, MC AF Meulendyke, Kelly A. Queen, Suzanne E. Engle, Elizabeth L. Shirk, Erin N. Liu, Jiayang Steiner, Joseph P. Nath, Avindra Tarwater, Patrick M. Graham, David R. Mankowski, Joseph L. Zink, M. Christine TI Combination fluconazole/paroxetine treatment is neuroprotective despite ongoing neuroinflammation and viral replication in an SIV model of HIV neurological disease SO JOURNAL OF NEUROVIROLOGY LA English DT Article DE HIV; SIV; Fluconazole; Paroxetine; Selective serotonin reuptake inhibitor; CNS ID CENTRAL-NERVOUS-SYSTEM; IMMUNODEFICIENCY VIRUS ENCEPHALITIS; BETA-AMYLOID PRECURSOR; NEUROCOGNITIVE DISORDERS; CEREBROSPINAL-FLUID; OXIDATIVE STRESS; NEUROFILAMENT PROTEIN; NEURONAL PLASTICITY; BEHAVIORAL DEFICITS; MACAQUE MODEL AB Effective combined antiretroviral therapy (cART) in HIV-infected patients has made HIV a treatable infection; however, debilitating HIV-associated neurocognitive disorders (HAND) can still affect approximately 50 % of HIV-infected individuals even under cART. While cART has greatly reduced the prevalence of the most severe form of HAND, milder forms have increased in prevalence, leaving the total proportion of HIV-infected individuals suffering from HAND relatively unchanged. In this study, an in vitro drug screen identified fluconazole and paroxetine as protective compounds against HIV gp120 and Tat neurotoxicity. Using an accelerated, consistent SIV/macaque model of HIV-associated CNS disease, we tested the in vivo neuroprotective capabilities of combination fluconazole/paroxetine (FluPar) treatment. FluPar treatment protected macaques from SIV-induced neurodegeneration, as measured by neurofilament light chain in the CSF, APP accumulation in axons, and CaMKII alpha in the frontal cortex, but did not significantly reduce markers of neuroinflammation or plasma or CNS viral loads. Since HIV and SIV neurodegeneration is often attributed to accompanying neuroinflammation, this study provides proof of concept that neuroprotection can be achieved even in the face of ongoing neuroinflammation and viral replication. C1 [Meulendyke, Kelly A.; Queen, Suzanne E.; Engle, Elizabeth L.; Shirk, Erin N.; Graham, David R.; Mankowski, Joseph L.; Zink, M. Christine] Johns Hopkins Univ, Sch Med, Dept Mol & Comparat Pathobiol, Baltimore, MD 21205 USA. [Liu, Jiayang; Tarwater, Patrick M.] Texas Tech Univ, Hlth Sci Ctr, Foster Sch Med, Dept Biostat & Epidemiol, El Paso, TX USA. [Steiner, Joseph P.] NINDS, Translat Neurosci Ctr, NIH, Bethesda, MD 20892 USA. [Nath, Avindra] NINDS, Sect Infect Nervous Syst, NIH, Bethesda, MD 20892 USA. RP Zink, MC (reprint author), Johns Hopkins Univ, Sch Med, Dept Mol & Comparat Pathobiol, 733 North Broadway St,MRB 819, Baltimore, MD 21205 USA. EM mczink@jhmi.edu FU National Institutes of Health [P30 MH075673, R01 MH087233, R01 MH085554, P01 MH070306, P40 OD013117] FX These studies were funded by the National Institutes of Health (grants P30 MH075673, R01 MH087233, R01 MH085554, P01 MH070306, and P40 OD013117). NR 60 TC 5 Z9 5 U1 0 U2 4 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1355-0284 EI 1538-2443 J9 J NEUROVIROL JI J. Neurovirol. PD DEC PY 2014 VL 20 IS 6 BP 591 EP 602 DI 10.1007/s13365-014-0283-1 PG 12 WC Neurosciences; Virology SC Neurosciences & Neurology; Virology GA AW4FX UT WOS:000346237700005 PM 25227932 ER PT J AU Sacktor, N Miyahara, S Evans, S Schifitto, G Cohen, B Haughey, N Drewes, JL Graham, D Zink, MC Anderson, C Nath, A Pardo, CA McCarthy, S Hosey, L Clifford, D AF Sacktor, Ned Miyahara, Sachiko Evans, Scott Schifitto, Giovanni Cohen, Bruce Haughey, Norman Drewes, Julia L. Graham, David Zink, M. Christine Anderson, Caroline Nath, Avindra Pardo, Carlos A. McCarthy, Sean Hosey, Lara Clifford, David CA ACTG A5235 Team TI Impact of minocycline on cerebrospinal fluid markers of oxidative stress, neuronal injury, and inflammation in HIV-seropositive individuals with cognitive impairment SO JOURNAL OF NEUROVIROLOGY LA English DT Article DE Minocycline; HIV; Cognitive; Oxidative; Stress; Biomarker ID NERVOUS-SYSTEM; DEMENTIA; CERAMIDE; METABOLISM; INFECTION; TRIAL; BRAIN AB Elevated cerebrospinal fluid (CSF) levels of markers of oxidative stress, neuronal injury, and inflammation and decreased neurotransmitter levels have been reported in HIV-associated neurocognitive disorders (HAND). Minocycline may have a neuroprotective effect by inhibiting inducible nitric oxide synthase, which produces nitric oxide, a compound that induces oxygen free radical production. In A5235, "Phase II, Randomized, Placebo-Controlled, Double-Blind Study of Minocycline in the Treatment of HIV-Associated Cognitive Impairment," minocycline was not associated with cognitive improvement, but the effect on the above CSF measures was not examined previously. The objective of this study was to examine the effect of minocycline on markers of oxidative stress, neuronal injury, neurotransmitter levels, and inflammation from CSF in participants in A5235. One hundred seven HIV+ individuals received either minocycline 100 mg or placebo orally every 12 h for 24 weeks. Twenty-one HIV+ individuals received the optional lumbar punctures. Lipid and protein markers of oxidative stress (e.g., ceramides and protein carbonyls), glutamate, neurotransmitter precursors, kynurenine metabolites, neurofilament heavy chain, and inflammatory cytokines were measured in the CSF before and after treatment. The 24-week change in ceramides was larger in a beneficial direction in the minocycline group compared to the placebo group. The two groups did not differ in the 24-week changes for other markers. These results suggest that minocycline may decrease lipid markers of oxidative stress (ceramides) in individuals with HAND; however, an effect of minocycline on other CSF markers was not observed. A larger sample size is needed to further validate these results. C1 [Sacktor, Ned; Haughey, Norman; Drewes, Julia L.; Graham, David; Zink, M. Christine; Pardo, Carlos A.] Johns Hopkins Univ, Sch Med, Baltimore, MD 21205 USA. [Miyahara, Sachiko; Evans, Scott] Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA. [Schifitto, Giovanni] Univ Rochester, Rochester, NY USA. [Cohen, Bruce] Northwestern Univ, Chicago, IL 60611 USA. [Anderson, Caroline; Nath, Avindra] NIH, Bethesda, MD 20892 USA. [McCarthy, Sean; Hosey, Lara] AIDS Clin Trials Grp ACTG Operat Ctr, Silver Spring, MD USA. [Clifford, David] Washington Univ, St Louis, MO USA. RP Sacktor, N (reprint author), Johns Hopkins Univ, Sch Med, Baltimore, MD 21205 USA. EM sacktor@jhmi.edu FU AIDS Clinical Trials Group (ACTG) - NIAID [AI38858, AI38855, AI27670, AI27668, AI27658, AI34853, AI127660, AI27664, AI27659, AI25903, AI25915, AI046376, AI46370, AI46381, AI50410, AI25868, AI46386, CFAR AI 127757]; AIDS Clinical Trials Group (ACTG) - Neurologic AIDS Research Consortium [NS32228, NS081196, NS055628, MH075673, MH64409, AI 068634]; GCRC Units - National Center for Research Resources (NCRR) [RR00052, RR00044, RR00046]; University of California, San Diego Antiviral Research CTU [AI069432]; Johns Hopkins University CTU [AI069465]; CTSA [UL1 RR025005]; UCLA School of Medicine CTU [AI069424]; Washington University (St. Louis) CTU [AI069495]; Research & Education Group-Portland CRS CTU [AI069503]; Henry Ford Hospital CRS CTU [AI069503]; Massachusetts General Hospital CTU [AI069472]; NYU/NYC HHC at Bellevue CTU [AI069532]; Univ. of Colorado Hospital CTU [AI069450]; Northwestern University CTU [AI069471]; Virginia Commonwealth University Medical Center CRS CTU [AI069503]; University of Washington (Seattle) CTU [AI069434]; University of North Carolina CTU [AI069423]; University of Rochester Medical Center CTU [AI069511]; Emory University, The Ponce de Leon Center CTU [AI069452]; University of Pennsylvania, Philadelphia CTU [AI069467-04]; National Institute of Allergy and Infectious Diseases, National Institute of Mental Health (NIMH) [AI068636]; National Institute of Dental and Craniofacial Research (NIDCR) FX The authors would like to thank Marie Sonderman for administrative support. The statistical analysis was carried out by S. Miyahara. This study was supported in part by the AIDS Clinical Trials Group (ACTG) funded by the following: NIAID, AI38858, AI38855, AI27670, AI27668, AI27658, AI34853, AI127660, AI27664, AI27659, AI25903, AI25915, AI046376, AI46370, AI46381, AI50410, AI25868, AI46386, CFAR AI 127757, the Neurologic AIDS Research Consortium, NS32228, NS081196, NS055628, MH075673, MH64409, AI 068634 and GCRC Units funded by the National Center for Research Resources (NCRR), RR00052, RR00044, RR00046. The NCT number for this study is NCT 00361257. This study is registered in Clinical Trials.gov. Participating site ACTG Clinical Trials Unit (CTU) grant numbers include the following:; University of California, San Diego Antiviral Research CTU Grant AI069432; Johns Hopkins University CTU Grant AI069465; CTSA Grant UL1 RR025005; UCLA School of Medicine CTU Grant AI069424; Washington University (St. Louis) CTU Grant AI069495; The Research & Education Group-Portland CRS CTU Grant AI069503; Henry Ford Hospital CRS CTU Grant AI069503; Massachusetts General Hospital CTU Grant AI069472; NYU/NYC HHC at Bellevue CTU Grant AI069532; Univ. of Colorado Hospital CTU Grant AI069450; Northwestern University CTU Grant AI069471; Virginia Commonwealth University Medical Center CRS CTU Grant AI069503; University of Washington (Seattle) CTU Grant AI069434; University of North Carolina CTU Grant AI069423; University of Rochester Medical Center CTU Grant AI069511; Emory University, The Ponce de Leon Center CTU Grant AI069452; and University of Pennsylvania, Philadelphia CTU Grant AI069467-04.; The project described was supported by Award Number AI068636 from the National Institute of Allergy and Infectious Diseases, National Institute of Mental Health (NIMH), and National Institute of Dental and Craniofacial Research (NIDCR). The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institute of Allergy and Infectious Diseases or the National Institutes of Health. NR 22 TC 8 Z9 8 U1 0 U2 3 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1355-0284 EI 1538-2443 J9 J NEUROVIROL JI J. Neurovirol. PD DEC PY 2014 VL 20 IS 6 BP 620 EP 626 DI 10.1007/s13365-014-0292-0 PG 7 WC Neurosciences; Virology SC Neurosciences & Neurology; Virology GA AW4FX UT WOS:000346237700008 PM 25377444 ER PT J AU Ward, RE Boudreau, RM Caserotti, P Harris, TB Zivkovic, S Goodpaster, BH Satterfield, S Kritchevsky, SB Schwartz, AV Vinik, AI Cauley, JA Simonsick, EM Newman, AB Strotmeyer, ES AF Ward, Rachel E. Boudreau, Robert M. Caserotti, Paolo Harris, Tamara B. Zivkovic, Sasa Goodpaster, Bret H. Satterfield, Suzanne Kritchevsky, Stephen B. Schwartz, Ann V. Vinik, Aaron I. Cauley, Jane A. Simonsick, Eleanor M. Newman, Anne B. Strotmeyer, Elsa S. CA Hlth Aging Body Composition Study TI Sensory and Motor Peripheral Nerve Function and Incident Mobility Disability SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY LA English DT Article DE peripheral nerve function; disability; older adults; longitudinal analysis; muscle strength ID MUSCLE STRENGTH; OLDER-ADULTS; BODY-COMPOSITION; PHYSICAL PERFORMANCE; DIABETIC-NEUROPATHY; WOMENS HEALTH; AGE; CONDUCTION; BLACK; DEGENERATION AB ObjectivesTo assess the relationship between sensorimotor nerve function and incident mobility disability over 10years. DesignProspective cohort study with longitudinal analysis. SettingTwo U.S. clinical sites. ParticipantsPopulation-based sample of community-dwelling older adults with no mobility disability at 2000/01 examination (N=1,680; mean age SD 76.52.9, body mass index 27.14.6; 50.2% female, 36.6% black, 10.7% with diabetes mellitus). MeasurementsMotor nerve conduction amplitude (poor <1 mV) and velocity (poor <40m/s) were measured on the deep peroneal nerve. Sensory nerve function was measured using 10- and 1.4-g monofilaments and vibration detection threshold at the toe. Lower extremity symptoms included numbness or tingling and aching or burning pain. Incident mobility disability assessed semiannually over 8.5years (interquartile range 4.5-9.6years) was defined as two consecutive self-reports of a lot of difficulty or inability to walk one-quarter of a mile or climb 10 steps. ResultsNerve impairments were detected in 55% of participants, and 30% developed mobility disability. Worse motor amplitude (HR=1.29 per SD, 95% CI=1.16-1.44), vibration detection threshold (HR=1.13 per SD, 95% CI=1.04-1.23), symptoms (HR=1.65, 95% CI=1.26-2.17), two motor impairments (HR=2.10, 95% CI=1.43-3.09), two sensory impairments (HR=1.91, 95% CI=1.37-2.68), and three or more nerve impairments (HR=2.33, 95% CI=1.54-3.53) predicted incident mobility disability after adjustment. Quadriceps strength mediated relationships between certain nerve impairments and mobility disability, although most remained significant. ConclusionPoor sensorimotor nerve function independently predicted mobility disability. Future work should investigate modifiable risk factors and interventions such as strength training for preventing disability and improving function in older adults with poor nerve function. C1 [Ward, Rachel E.] Spaulding Rehabil Hosp, Cambridge, England. [Ward, Rachel E.] Boston Univ, Sch Publ Hlth, Boston, MA USA. [Boudreau, Robert M.; Cauley, Jane A.; Newman, Anne B.; Strotmeyer, Elsa S.] Univ Pittsburgh, Grad Sch Publ Hlth, Dept Epidemiol, Pittsburgh, PA 15213 USA. [Caserotti, Paolo] Univ Southern Denmark, Inst Sports Sci & Clin Biomech, Odense, Denmark. [Harris, Tamara B.] NIA, Lab Epidemiol Biometry & Demog, NIH, Bethesda, MD USA. [Zivkovic, Sasa] Univ Pittsburgh, Sch Med, Dept Neurol, Pittsburgh, PA 15213 USA. [Zivkovic, Sasa] Vet Affairs Pittsburgh Hlth Care Syst, Pittsburgh, PA USA. [Goodpaster, Bret H.] Univ Pittsburgh, Sch Med, Dept Med, Pittsburgh, PA 15213 USA. [Satterfield, Suzanne] Univ Tennessee, Dept Prevent Med, Memphis, TN USA. [Kritchevsky, Stephen B.] Wake Forest, Div Gerontol & Geriatr Med, Dept Internal Med, Winston Salem, NC USA. [Schwartz, Ann V.] Univ Calif San Francisco, Dept Epidemiol & Biostat, San Francisco, CA 94143 USA. [Vinik, Aaron I.] Eastern Virginia Med Sch, Dept Neurobiol, Norfolk, VA 23501 USA. [Simonsick, Eleanor M.] NIA, Translat Gerontol Branch, NIH, Baltimore, MD 21224 USA. RP Strotmeyer, ES (reprint author), Univ Pittsburgh, Dept Epidemiol, 130 N Bellefield Ave,Rm 515, Pittsburgh, PA 15213 USA. EM StrotmeyerE@edc.pitt.edu RI Cauley, Jane/N-4836-2015; Newman, Anne B./C-6408-2013; OI Cauley, Jane/0000-0003-0752-4408; Newman, Anne B./0000-0002-0106-1150; Strotmeyer, Elsa/0000-0002-4093-6036; Boudreau, Robert/0000-0003-0162-5187 FU National Institute on Aging [N01-AG-6-2101, N01-AG-6-2103, N01-AG-6-2106, 1-R01-AG 028050]; National Institute of Nursing Research Grant [R01-NR012459]; Intramural Research Program of the National Institutes of Health, National Institute on Aging; University of Pittsburgh Claude D. Pepper Older Americans Independence Center [P30-AG024827]; American Diabetes Association [1-04-JF-46] FX This research was supported by National Institute on Aging Contracts N01-AG-6-2101, N01-AG-6-2103, and N01-AG-6-2106 and Grant 1-R01-AG 028050 (to ESS) and National Institute of Nursing Research Grant R01-NR012459 and supported in part by the Intramural Research Program of the National Institutes of Health, National Institute on Aging, the University of Pittsburgh Claude D. Pepper Older Americans Independence Center (P30-AG024827) Pilot Grant (to ESS), and the American Diabetes Association (1-04-JF-46 to ESS). NR 33 TC 10 Z9 10 U1 1 U2 6 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0002-8614 EI 1532-5415 J9 J AM GERIATR SOC JI J. Am. Geriatr. Soc. PD DEC PY 2014 VL 62 IS 12 BP 2273 EP 2279 DI 10.1111/jgs.13152 PG 7 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA AW8FX UT WOS:000346497600005 PM 25482096 ER PT J AU Wang, WD Qiu, LR Howard, A Solis, N Li, CL Wang, XX Kopp, JB Levi, M AF Wang, Weidong Qiu, Liru Howard, Allison Solis, Nathaniel Li, Chunling Wang, Xiaoxin Kopp, Jeffrey B. Levi, Moshe TI Protective effects of aliskiren and valsartan in mice with diabetic nephropathy SO JOURNAL OF THE RENIN-ANGIOTENSIN-ALDOSTERONE SYSTEM LA English DT Article DE Albuminuria; renin inhibition; lipid metabolism; ER stress; diabetic nephropathy ID RENIN-ANGIOTENSIN SYSTEM; RENAL LIPID-METABOLISM; ENDOPLASMIC-RETICULUM-STRESS; CARDIORENAL END-POINTS; MESANGIAL CELLS; KIDNEY-DISEASE; ALDOSTERONE SYSTEM; GLUCOSE-METABOLISM; INSULIN-RESISTANCE; ACE-INHIBITION AB Aim: We investigated whether aliskiren, a direct renin inhibitor, provided protection in a model of diabetic nephropathy in mice and compared its protective effects to valsartan, an angiotensin II type 1 receptor blocker. Materials and methods: Hyperglycemia was induced with streptozotocin (STZ, 40 mg/kg/day x 5 days) injection in DBA/2J mice fed on a high fat diet. Mice were treated with either aliskiren (25 mg/kg/day) or valsartan (8 mg/kg/day) for 6 weeks. Results: Aliskiren and/or valsartan treatment significantly attenuated albuminuria, urinary nephrin excretion and glomerulosclerosis. Aliskiren and/or valsartan prevented reduction of podocin and WT1 protein abundance in diabetic mice. Aliskiren and/or valsartan significantly prevented increased expression of profibrotic growth factors (TGF, CTGF and PAI-1), proinflammatory cytokines (MCP-1, TNF and IL-1), endoplasmic reticulum (ER) stress markers (CHOP and XBP-1) and lipid accumulation in the kidney of diabetic animals. Aliskiren showed similar efficacy compared to valsartan therapy and dual treatment in some aspects has synergistic protective effects. Conclusion: Our study indicates that aliskiren and/or valsartan protects against diabetic kidney disease through multiple mechanisms, including decreasing podocyte injury, activation of profibrotic growth factors and proinflammatory cytokines, ER stress and accumulation of lipids. C1 [Wang, Weidong; Qiu, Liru; Howard, Allison; Solis, Nathaniel; Wang, Xiaoxin; Levi, Moshe] Univ Colorado, Dept Med, Div Renal Dis & Hypertens, Boulder, CO 80309 USA. [Wang, Weidong; Li, Chunling] Sun Yat Sen Univ, Zhongshan Sch Med, Inst Hypertens & Kidney Res, Guangzhou 510080, Guangdong, Peoples R China. [Kopp, Jeffrey B.] NIDDK, Kidney Dis Sect, NIH, Bethesda, MD 20892 USA. RP Wang, WD (reprint author), Sun Yat Sen Univ, Zhongshan Sch Med, Inst Hypertens & Kidney Res, 74 Zhongshan Er Rd, Guangzhou 510080, Guangdong, Peoples R China. EM wangwd6@mail.sysu.edu.cn OI Kopp, Jeffrey/0000-0001-9052-186X FU Novartis Medical School IISS; NIH [R01 AG026529]; Novartis grants; Natural Science Foundation of China [81370822]; Guangdong Nature Science Foundation [S2013010015499] FX This work was supported by grants from Grants from Novartis Medical School IISS and NIH R01 AG026529. WW was supported by Novartis grants. This work was also supported by the Natural Science Foundation of China (Grant No. 81370822) and Guangdong Nature Science Foundation (Grant No. S2013010015499). NR 54 TC 13 Z9 14 U1 3 U2 6 PU SAGE PUBLICATIONS LTD PI LONDON PA 1 OLIVERS YARD, 55 CITY ROAD, LONDON EC1Y 1SP, ENGLAND SN 1470-3203 EI 1752-8976 J9 J RENIN-ANGIO-ALDO S JI J. Renin-Angiotensin-Aldosterone Syst. PD DEC PY 2014 VL 15 IS 4 BP 384 EP 395 DI 10.1177/1470320313507123 PG 12 WC Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA AW4SA UT WOS:000346269600007 PM 25031296 ER PT J AU Blumenfeld, YJ Momirova, V Rouse, DJ Caritis, SN Sciscione, A Peaceman, AM Reddy, UM Varner, MW Malone, FD Iams, JD Mercer, BM Thorp, JM Sorokin, Y Carpenter, MW Lo, J Ramin, SM Harper, M AF Blumenfeld, Yair J. Momirova, Valerija Rouse, Dwight J. Caritis, Steve N. Sciscione, Anthony Peaceman, Alan M. Reddy, Uma M. Varner, Michael W. Malone, Fergal D. Iams, Jay D. Mercer, Brian M. Thorp, John M., Jr. Sorokin, Yoram Carpenter, Marshall W. Lo, Julie Ramin, Susan M. Harper, Margaret CA Eunice Kennedy Shriver Natl Inst TI Accuracy of Sonographic Chorionicity Classification in Twin Gestations SO JOURNAL OF ULTRASOUND IN MEDICINE LA English DT Article DE accuracy; chorionicity; obstetric ultrasound; sonography; twins ID PREGNANT-WOMEN; AMNIONICITY; PREDICTION; STILLBIRTH; ULTRASOUND; DIAGNOSIS; COHORT; RISK AB Objectives-To evaluate the accuracy of sonographic classification of chorionicity in a large cohort of twins and investigate which factors maybe associated with sonographic accuracy. Methods-We conducted a secondary analysis of a randomized trial of preterm birth prevention in twins. Sonographic classification of chorionicity was compared with pathologic examination of the placenta. Maternal (age, body mass index, diabetes, and hypertension), obstetric (prior cesarean delivery, gestational age at the first sonographic examination, and antepartum bleeding), and sonographic (oligohydramnios, polyhydramnios, and twin-twin transfusion syndrome) factors were assessed for their possible association with accuracy. Results-A total of 545 twin sets in which chorionicity was classified by sonography before 20 weeks' gestation were included; 455 were dichorionic and 90 were monochorionic based on pathologic examination. Sonography misclassified 35 of 545 twin pregnancies (6.4%): 18 of 455 dichorionic twins (4.0%) and 17 of 90 monochorionic twins (19.0%). The sensitivity and specificity of sonographic diagnosis of monochorionicity were 81.1% and 96.0%, respectively. In a multivariable analysis, pregnancies with initial sonographic examinations before 14 weeks' gestation were less likely to have misclassified chorionicity than those with sonographic examinations at 15 to 20 weeks (odds ratio [On 0.47; 95% confidence interval [CI], 0.23-0.96). For each week increase in gestational age, the odds of misclassification rose by 10% (OR, 1.10; 95% CI, 1.01-1.2). In the multivariable analysis, maternal age, body mass index, parity, and prior cesarean delivery were not associated with sonographic accuracy. Conclusions-Sonography before 20 weeks incorrectly classified chorionicity in 6.4% of twin gestations. Those with first sonographic examinations performed at earlier gestational ages had improved chorionicity diagnosis. C1 [Blumenfeld, Yair J.] Stanford Univ, Sch Med, Dept Obstet & Gynecol, Stanford, CA 94305 USA. [Momirova, Valerija] George Washington Univ, Ctr Biostat, Washington, DC USA. [Rouse, Dwight J.] Univ Alabama Birmingham, Dept Obstet & Gynecol, Birmingham, AL 35294 USA. [Caritis, Steve N.] Univ Pittsburgh, Pittsburgh, PA USA. [Sciscione, Anthony] Drexel Univ, Philadelphia, PA 19104 USA. [Peaceman, Alan M.] Northwestern Univ, Chicago, IL 60611 USA. [Reddy, Uma M.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Bethesda, MD USA. [Varner, Michael W.] Univ Utah, Salt Lake City, UT USA. [Malone, Fergal D.] Columbia Univ, New York, NY USA. [Iams, Jay D.] Ohio State Univ, Columbus, OH 43210 USA. [Mercer, Brian M.] Case Western Reserve Univ, Metrohlth Med Ctr, Cleveland, OH USA. [Thorp, John M., Jr.] Univ N Carolina, Chapel Hill, NC USA. [Sorokin, Yoram] Wayne State Univ, Detroit, MI USA. [Carpenter, Marshall W.] Brown Univ, Providence, RI 02912 USA. [Lo, Julie] Univ Texas SW Med Ctr Dallas, Dallas, TX 75390 USA. [Ramin, Susan M.] Univ Texas Hlth Sci Ctr Houston, Houston, TX 77030 USA. [Harper, Margaret] Wake Forest Univ Hlth Sci, Winston Salem, NC USA. RP Blumenfeld, YJ (reprint author), Stanford Univ, Sch Med, Dept Obstet & Gynecol, Div Maternal Fetal Med, 300 Pasteur Dr,Room HH333, Stanford, CA 94305 USA. EM yairb@stanford.edu RI Varner, Michael/K-9890-2013 OI Varner, Michael/0000-0001-9455-3973 FU Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) [HD27869, HD21410, HD40512, HD34136, HD34208, HD40485, HD27915, HD40544, HD40560, HD27917, HD40500, HD34116, HD40545, HD27860, HD36801]; National Center for Research Resources [M01 RR00080, UL1 RR024989] FX We thank the following subcommittee members who participated in protocol development and coordination between clinical research centers (Margaret Cotroneo, RN, and Allison T. Northen, MSN, RN), protocol/data management and statistical analysis (Elizabeth Thom, PhD), and protocol development and oversight (Catherine Y. Spong, MD). This project was supported by grants from the Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD; HD27869, HD21410, HD40512, HD34136, HD34208, HD40485, HD27915, HD40544, HD40560, HD27917, HD40500, HD34116, HD40545, HD27860, and HD36801) and the National Center for Research Resources (M01 RR00080 and UL1 RR024989); its contents do not necessarily represent the official view of the NICHD, National Heart, Lung, and Blood Institute, National Center for Research Resources, or National Institutes of Health. Source of the study: NICHD Maternal-Fetal Medicine Units Network Trial of Progesterone in Twins and Triplets to Prevent Preterm Birth study (clinicaltrials.gov number NCT00099164). The study was presented at the 2013 American Institute of Ultrasound in Medicine Annual Convention; April 6-10, 2013; New York, New York. NR 20 TC 8 Z9 8 U1 0 U2 2 PU AMER INST ULTRASOUND MEDICINE PI LAUREL PA SUBSCRIPTION DEPT, 14750 SWEITZER LANE, STE 100, LAUREL, MD 20707-5906 USA SN 0278-4297 EI 1550-9613 J9 J ULTRAS MED JI J. Ultrasound Med. PD DEC PY 2014 VL 33 IS 12 BP 2187 EP 2192 DI 10.7863/ultra.33.12.2187 PG 6 WC Acoustics; Radiology, Nuclear Medicine & Medical Imaging SC Acoustics; Radiology, Nuclear Medicine & Medical Imaging GA AW4DY UT WOS:000346232600017 PM 25425377 ER PT J AU Eudy, AM Vines, AI Dooley, MA Cooper, GS Parks, CG AF Eudy, A. M. Vines, A. I. Dooley, M. A. Cooper, G. S. Parks, C. G. TI Elevated C-reactive protein and self-reported disease activity in systemic lupus erythematosus SO LUPUS LA English DT Article DE Systemic lupus erythematosus; C-reactive protein; flares; socioeconomic factors ID ERYTHROCYTE SEDIMENTATION-RATE; SOUTHEASTERN UNITED-STATES; RHEUMATOID-ARTHRITIS; ACTIVITY QUESTIONNAIRE; SOCIOECONOMIC-STATUS; REVISED CRITERIA; HEALTH; DAMAGE; VALIDATION; AMERICAN AB C-reactive protein (CRP), a biomarker of inflammation, has been associated with increased disease activity in rheumatoid arthritis. However, the association in systemic lupus erythematosus (SLE) remains unclear. We examined the association of CRP with self-reported disease activity in the Carolina Lupus Study and described differences by sociodemographic characteristics. The study included baseline and three-year follow-up data on 107 African-American and 69 Caucasian SLE patients enrolled at a median 13 months since diagnosis. Models estimated prevalence differences in the association of baseline CRP with self-reported flares, adjusting for age, sex, race and education. Active disease or flare was reported by 59% at baseline and 58% at follow-up. Higher CRP (> 10 mu g/ml vs. <3 mu g/ml) was associated with a 17% (95% confidence interval (CI): -20, 53%) higher prevalence of flare at baseline and a 26% (95% CI: -9, 62%) higher prevalence of flare at follow-up. These CRP-flare associations were notably stronger in patients with lower education at baseline and in African-Americans at follow-up. These findings suggest that CRP may be a useful marker in studies of SLE health disparities. C1 [Eudy, A. M.; Vines, A. I.] Univ N Carolina, Dept Epidemiol, Gillings Sch Global Publ Hlth, Chapel Hill, NC 27599 USA. [Dooley, M. A.] Univ N Carolina, Chapel Hill, NC 27599 USA. [Cooper, G. S.] US EPA, Natl Ctr Environm Assessment, Washington, DC 20460 USA. [Parks, C. G.] NIEHS, Epidemiol Branch, NIH, DHHS, Durham, NC USA. RP Eudy, AM (reprint author), Univ N Carolina, Dept Epidemiol, Gillings Sch Global Publ Hlth, Campus Box 7435, Chapel Hill, NC 27599 USA. EM aeudy@email.unc.edu OI Eudy, Amanda/0000-0002-3107-5545; Parks, Christine/0000-0002-5734-3456 FU Intramural Research Program of the NIEHS; National Center for Minority Health and Health Disparities of the NIH FX This work was supported by the Intramural Research Program of the NIEHS and the National Center for Minority Health and Health Disparities of the NIH. NR 36 TC 3 Z9 3 U1 1 U2 5 PU SAGE PUBLICATIONS LTD PI LONDON PA 1 OLIVERS YARD, 55 CITY ROAD, LONDON EC1Y 1SP, ENGLAND SN 0961-2033 EI 1477-0962 J9 LUPUS JI Lupus PD DEC PY 2014 VL 23 IS 14 BP 1460 EP 1467 DI 10.1177/0961203314543915 PG 8 WC Rheumatology SC Rheumatology GA AW3HK UT WOS:000346177000003 PM 25057037 ER PT J AU Lee, M Dworkin, AM Lichtenberg, J Patel, SJ Trivedi, NS Gildea, D Bodine, DM Crawford, NPS AF Lee, Minnkyong Dworkin, Amy M. Lichtenberg, Jens Patel, Shashank J. Trivedi, Niraj S. Gildea, Derek Bodine, David M. Crawford, Nigel P. S. TI Metastasis-Associated Protein Ribosomal RNA Processing 1 Homolog B (RRP1B) Modulates Metastasis through Regulation of Histone Methylation SO MOLECULAR CANCER RESEARCH LA English DT Article ID ZINC-FINGER PROTEINS; BREAST-CANCER; TRANSCRIPTIONAL REPRESSION; C-MYC; GENOME; EXPRESSION; SIGNATURE; INTERACTS; SURVIVAL; DATABASE AB Overexpression of ribosomal RNA processing 1 homolog B (RRP1B) induces a transcriptional profile that accurately predicts patient outcome in breast cancer. However, the mechanism by which RRP1B modulates transcription is unclear. Here, the chromatin-binding properties of RRP1B were examined to define how it regulates metastasis-associated transcription. To identify genome-wide RRP1B-binding sites, high-throughput ChIP-seq was performed in the human breast cancer cell line MDA-MB-231 and HeLa cells using antibodies against endogenous RRP1B. Global changes in repressive marks such as histone H3 lysine 9 trimethylation (H3K9me3) were also examined by ChIP-seq. Analysis of these samples identified 339 binding regions in MDA-MB-231 cells and 689 RRP1B-binding regions in HeLa cells. Among these, 136 regions were common to both cell lines. Gene expression analyses of these RRP1B-binding regions revealed that transcriptional repression is the primary result of RRP1B binding to chromatin. ChIP-reChIP assays demonstrated that RRP1B co-occupies loci with decreased gene expression with the heterochromatin-associated proteins, tripartite motif-containing protein 28 (TRIM28/KAP1), and heterochromatin protein 1-alpha (CBX5/HP1 alpha). RRP1B occupancy at these loci was also associated with higher H3K9me3 levels, indicative of heterochromatinization mediated by the TRIM28/HP1 alpha complex. In addition, RRP1B upregulation, which is associated with metastasis suppression, induced globalchanges in histone methylation. (C) 2014 AACR. C1 [Lee, Minnkyong; Dworkin, Amy M.; Lichtenberg, Jens; Patel, Shashank J.; Bodine, David M.; Crawford, Nigel P. S.] NHGRI, Genet & Mol Biol Branch, NIH, Bethesda, MD 20892 USA. [Trivedi, Niraj S.; Gildea, Derek] NHGRI, Genome Technol Branch, NIH, Bethesda, MD 20892 USA. RP Crawford, NPS (reprint author), NHGRI, NIH, 50 South Dr Rm 5154, Bethesda, MD 20892 USA. EM crawforn@mail.nih.gov FU Intramural Research Program of the National Human Genome Research Institute, NIH FX This work was supported by the Intramural Research Program of the National Human Genome Research Institute, NIH. NR 37 TC 5 Z9 5 U1 0 U2 2 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1541-7786 EI 1557-3125 J9 MOL CANCER RES JI Mol. Cancer Res. PD DEC PY 2014 VL 12 IS 12 BP 1818 EP 1828 DI 10.1158/1541-7786.MCR-14-0167 PG 11 WC Oncology; Cell Biology SC Oncology; Cell Biology GA AW9EN UT WOS:000346560400011 PM 25092915 ER PT J AU Johnson, IRD Parkinson-Lawrence, EJ Shandala, T Weigert, R Butler, LM Brooks, DA AF Johnson, Ian R. D. Parkinson-Lawrence, Emma J. Shandala, Tetyana Weigert, Roberto Butler, Lisa M. Brooks, Doug A. TI Altered Endosome Biogenesis in Prostate Cancer Has Biomarker Potential SO MOLECULAR CANCER RESEARCH LA English DT Article ID CATHEPSIN-B; CELL-LINES; ACID-PHOSPHATASE; ADAPTER PROTEIN; RAB PROTEINS; TRAFFICKING; PROGRESSION; STATISTICS; MORPHOLOGY; SECRETION AB Prostate cancer is the second most common form of cancer in males, affecting one in eight men by the time they reach the age of 70 years. Current diagnostic tests for prostate cancer have significant problems with both false negatives and false positives, necessitating the search for new molecular markers. A recent investigation of endosomal and lysosomal proteins revealed that the critical process of endosomal biogenesis might be altered in prostate cancer. Here, a panel of endosomal markers was evaluated in prostate cancer and nonmalignant cells and a significant increase in gene and protein expression was found for early, but not late endosomal proteins. There was also a differential distribution of early endosomes, and altered endosomal traffic and signaling of the transferrin receptors (TFRC and TFR2) in prostate cancer cells. These findings support the concept that endosome biogenesis and function are altered in prostate cancer. Microarray analysis of a clinical cohort confirmed the altered endosomal gene expression observed in cultured prostate cancer cells. Furthermore, in prostate cancer patient tissue specimens, the early endosomal marker and adaptor protein APPL1 showed consistently altered basement membrane histology in the vicinity of tumors and concentrated staining within tumor masses. These novel observations on altered early endosome biogenesis provide a new avenue for prostate cancer biomarker investigation and suggest new methods for the early diagnosis and accurate prognosis of prostate cancer. (C) 2014 AACR. C1 [Johnson, Ian R. D.; Parkinson-Lawrence, Emma J.; Shandala, Tetyana; Brooks, Doug A.] Univ S Australia, Sch Pharm & Med Sci, Sansom Inst Hlth Res, Mech Cell Biol & Dis Res Grp Leader, Adelaide, SA 5001, Australia. [Weigert, Roberto] NIDCR, NIH, Bethesda, MD USA. [Butler, Lisa M.] Univ Adelaide, Sch Med, Dame Roma Mitchell Canc Res Lab, Adelaide, SA, Australia. [Butler, Lisa M.] Univ Adelaide, Sch Med, Adelaide Prostate Canc Res Ctr, Adelaide, SA, Australia. RP Brooks, DA (reprint author), Univ S Australia, Sch Pharm & Med Sci, Sansom Inst Hlth Res, Mech Cell Biol & Dis Res Grp Leader, GPO Box 2471, Adelaide, SA 5001, Australia. EM Doug.Brooks@unisa.edu.au RI Brooks, Doug/K-6714-2012; di Ronza, Alberto/H-7674-2016; OI di Ronza, Alberto/0000-0002-9813-5143; Johnson, Ian/0000-0001-7875-3510 FU University of South Australia Presidents Scholarship; University of South Australia Postgraduate Award; University of South Australia Research SA Seeding Funds FX This project was funded by a University of South Australia Presidents Scholarship and a University of South Australia Postgraduate Award, together with additional support from University of South Australia Research SA Seeding Funds. NR 51 TC 5 Z9 5 U1 0 U2 3 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1541-7786 EI 1557-3125 J9 MOL CANCER RES JI Mol. Cancer Res. PD DEC PY 2014 VL 12 IS 12 BP 1851 EP 1862 DI 10.1158/1541-7786.MCR-14-0074 PG 12 WC Oncology; Cell Biology SC Oncology; Cell Biology GA AW9EN UT WOS:000346560400014 PM 25080433 ER PT J AU Haddad, MR Patel, KD Sullivan, PH Goldstein, DS Murphy, KM Centeno, JA Kaler, SG AF Haddad, Marie Reine Patel, Keyur D. Sullivan, Patricia H. Goldstein, David S. Murphy, Kevin M. Centeno, Jose A. Kaler, Stephen G. TI Molecular and biochemical characterization of Mottled-dappled, an embryonic lethal Menkes disease mouse model SO MOLECULAR GENETICS AND METABOLISM LA English DT Article DE Copper; Mottled-dappled; Menkes disease; Atp7a ID NEUROCHEMICAL ABNORMALITIES; NEONATAL DIAGNOSIS; ATP7A GENE; TRANSPORT; PLASMA; LOCALIZATION; TRAFFICKING; DELETION; PATTERN; PROTEIN AB Mottled-dappled (Mo-dp) is a mouse model of Menkes disease caused by a large, previously uncharacterized deletion in the 5' region of Atp7a, the mouse ortholog of ATP7A. Affected mutants die in utero at embryonic day 17, and show bending and thickening of the ribs and distortion of the pectoral and pelvic girdles and limbs. To characterize this allele, we designed a custom 4x180K microarray on the mouse X chromosome and performed comparative genomic hybridization using extracted DNA from normal and carrier Mo-dp females, and identified an approximately 9 kb deletion. We used PCR to fine-map the breakpoints and amplify a junction fragment of 630 bp. Sequencing of the junction fragment disclosed the exact breakpoint locations and that the Mo-dp deletion is precisely 8990 bp, including approximately 2 kb in the promoter region of Atp7a. Western blot analysis of Mo-dp heterozygous brains showed diminished amounts of Atp7a protein, consistent with reduced expression due to the promoter region deletion on one allele. In heterozygous females, brain copper levels tended to be lower compared to wild type whereas neurochemical analyses revealed higher dihydroxyphenylacetic acid: dihydroxyphenylglycol (DOPAC:DHPG) and dopamine:norepinephrine (DA:NE) ratios compared to normal (P = 0.002 and 0.029, respectively), consistent with partial deficiency of dopamine-beta-hydroxylase, a copper-dependent enzyme. Heterozygous females showed no significant differences in body weight compared to wild type females. Our results delineate the molecular details of the Mo-dp mutation for the first time and define novel biochemical findings in heterozygous female carriers of this allele. Published by Elsevier Inc. C1 [Haddad, Marie Reine; Patel, Keyur D.; Kaler, Stephen G.] NICHD, Sect Translat Neurosci, Program Mol Med, NIH, Bethesda, MD 20892 USA. [Sullivan, Patricia H.; Goldstein, David S.] NINDS, Clin Neurocardiol Sect, Clin Neurosci Program, NIH, Bethesda, MD 20892 USA. [Murphy, Kevin M.; Centeno, Jose A.] Andrews Air Force Base, Malcolm Grow Med Clin, Joint Pathol Ctr, Div Biophys Toxicol, Camp Springs, MD 20762 USA. RP Kaler, SG (reprint author), NICHD, Sect Translat Neurosci, Program Mol Med, NIH, 35A Convent Dr,Bldg 35A,Room 2D971,MSC 3754, Bethesda, MD 20892 USA. EM reina.haddad@nih.gov; keyur.patel19@gmail.com; psullivanl@ninds.nih.gov; goldsteind@ninds.nih.gov; kevin.m.murphy2@navy.mil; jose.centeno@afncr.af.mil; kalers@mail.nih.gov FU Intramural Research Program of the National Institutes of Health [Z01 HD008768] FX We thank Daniel Abebe, Lynn Holtzclaw, and Matt Schech for animal care support and assistance and Diego Martinelli for helpful discussions and comments. We also wish to acknowledge the late David Newsom (Nationwide Children's Hospital, Columbus, OH) for very helpful discussions and planning for array CGH. This work was supported by the Intramural Research Program of the National Institutes of Health Grant No. Z01 HD008768 (Disorders of Copper Transport). NR 27 TC 1 Z9 1 U1 0 U2 2 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1096-7192 EI 1096-7206 J9 MOL GENET METAB JI Mol. Genet. Metab. PD DEC PY 2014 VL 113 IS 4 BP 294 EP 300 DI 10.1016/j.ymgme.2014.10.001 PG 7 WC Endocrinology & Metabolism; Genetics & Heredity; Medicine, Research & Experimental SC Endocrinology & Metabolism; Genetics & Heredity; Research & Experimental Medicine GA AX0DG UT WOS:000346623000010 PM 25456742 ER PT J AU Kramar, CP Barbano, MF Medina, JH AF Kramar, Cecilia P. Flavia Barbano, M. Medina, Jorge H. TI Dopamine D1/D5 receptors in the dorsal hippocampus are required for the acquisition and expression of a single trial cocaine-associated memory SO NEUROBIOLOGY OF LEARNING AND MEMORY LA English DT Article DE Cocaine; Memory; Dopamine; Hippocampus; One-pairing CPP ID LONG-TERM-MEMORY; CONDITIONED PLACE PREFERENCE; NUCLEUS-ACCUMBENS CORE; MEDIAL PREFRONTAL CORTEX; REWARD MEMORY; BASOLATERAL AMYGDALA; SYNAPTIC PLASTICITY; SEEKING BEHAVIOR; D-1 RECEPTOR; CONSOLIDATION AB The role of the hippocampus in memory supporting associative learning between contexts and unconditioned stimuli is well documented. Hippocampal dopamine neurotransmission modulates synaptic plasticity and memory processing of fear-motivated and spatial learning tasks. Much less is known about the involvement of the hippocampus and its D1/D5 dopamine receptors in the acquisition, consolidation and expression of memories for drug-associated experiences, more particularly, in the processing of single pairing cocaine conditioned place preference (CPP) training. To determine the temporal dynamics of cocaine CPP memory formation, we trained rats in a one-pairing CPP paradigm and tested them at different time intervals after conditioning. The cocaine-associated memory lasted 24 h but not 72 h. Then, we bilaterally infused the dorsal hippocampus with the GABA A receptor agonist muscimol or the D1/D5 dopamine receptor antagonist SCH 23390 at different stages to evaluate the mechanisms involved in the acquisition, consolidation or expression of cocaine CPP memory. Blockade of D1/D5 dopamine receptors at the moment of training impaired the acquisition of cocaine CPP memories, without having any effect when administered immediately or 12 h after training. The expression of cocaine CPP memory was also affected by the administration of SCH 23390 at the moment of the test. Conversely, muscimol impaired the consolidation of cocaine CPP memory only when administered 12 h post conditioning. These findings suggests that dopaminergic inputs to the dorsal hippocampus are required for the acquisition and expression of one trial cocaine-associated memory while neural activity of this structure is required for the late consolidation of these types of memories. (C) 2014 Elsevier Inc. All rights reserved. C1 [Kramar, Cecilia P.; Flavia Barbano, M.; Medina, Jorge H.] Univ Buenos Aires, Fac Med, Inst Biol Celular & Neurociencias, CONICET UBA, Buenos Aires, DF, Argentina. [Flavia Barbano, M.] NIDA, Neuronal Networks Sect, NIH, Baltimore, MD USA. [Medina, Jorge H.] Univ Buenos Aires, Fac Med, Dept Fisiol, Buenos Aires, DF, Argentina. RP Medina, JH (reprint author), Univ Buenos Aires, Fac Med, Inst Biol Celular & Neurociencias, Paraguay 2155 3rd Floor,C1121ABG, Buenos Aires, DF, Argentina. EM jmedina@fmed.uba.ar FU CONICET, Argentina; CONICET [PIP 11420110100282]; UBA; Foncyt [PICT 2010-1169, PICT 2011-1941] FX We gratefully acknowledge Verardo y Cia. laboratory for their kind donation of cocaine hydrochloride. We would also like to thank Carolina Gonzalez and Fernando Castillo Diaz for excellent technical help and Pedro Bekinschtein for the revision of the manuscript. CP Kramar was supported by a doctoral fellowship from CONICET, Argentina. This work was supported by CONICET (Grant PIP 11420110100282 to Dr. Barbano), UBA and Foncyt (Grants PICT 2010-1169 to Dr. Medina and PICT 2011-1941 to Dr. Barbano). The authors declare no conflict of interests. NR 67 TC 6 Z9 6 U1 0 U2 7 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1074-7427 EI 1095-9564 J9 NEUROBIOL LEARN MEM JI Neurobiol. Learn. Mem. PD DEC PY 2014 VL 116 BP 172 EP 180 DI 10.1016/j.nlm.2014.10.004 PG 9 WC Behavioral Sciences; Neurosciences; Psychology; Psychology, Multidisciplinary SC Behavioral Sciences; Neurosciences & Neurology; Psychology GA AW6QN UT WOS:000346393800019 PM 25452086 ER PT J AU Grimes, CL Lukacz, ES Gantz, MG Warren, LK Brubaker, L Zyczynski, HM Richter, HE Jelovsek, JE Cundiff, G Fine, P Visco, AG Zhang, M Meikle, S AF Grimes, Cara L. Lukacz, Emily S. Gantz, Marie G. Warren, Lauren Klein Brubaker, Linda Zyczynski, Halina M. Richter, Holly E. Jelovsek, John Eric Cundiff, Geoffrey Fine, Paul Visco, Anthony G. Zhang, Min Meikle, Susan CA NICHD Pelvic Floor Disorders TI What Happens to the Posterior Compartment and Bowel Symptoms After Sacrocolpopexy?: Evaluation of 5-Year Outcomes From E-CARE SO OBSTETRICAL & GYNECOLOGICAL SURVEY LA English DT Editorial Material AB Posterior pelvic organ prolapse (pPOP) commonly occurs with apical prolapse, other vaginal compartment defects, and symptoms of defecatory dysfunction including obstructed defecation (OD). The indication for concomitant posterior repair (PR) during apical prolapse repair may be based on the presence or absence of symptoms. Some surgeons do not perform PR during repair of apical prolapse in the absence of symptoms. The Extended Colpopexy and Urinary Reduction Efforts (E-CARE) trial assessed the progression of posterior compartment prolapse and symptoms of OD after open abdominal sacrocolpopexy (ASC). Data from that study have been published in the primary article (Nygaard, JAMA 2013;309:2016). This secondary analysis of E-CARE data assessed the occurrence of pPOP and symptoms of OD in patients 5 years after open ASC. The study was designed to determine whether PR is necessary at the time of ASC. Participants with baseline and 5-year outcome data were divided into 3 groups using baseline posterior Pelvic Organ Prolapse Quantification points and concomitant PR: (1) no PR, Ap < 0; (2) no PR, Ap 0; and (3) +PR. Decision for concomitant PR was performed at the surgeon's discretion and included posterior colporrhaphy, perineorrhaphy, or sacrocolpoperineopexy. Five-year outcomes were dichotomized into presence/absence of pPOP (Ap > 0) and OD symptoms of moderate or greater bother (2) on 1 or more Pelvic Floor Distress Inventory questions about digital assistance, excessive straining, or incomplete evacuation. Composite failure during the 5-year interval was defined by both pPOP and OD symptoms or pPOP reoperation. Completed baseline and 5-year outcomes were available for 90 participants (60%); mean (SD) follow-up was 7.1 (1.0) years. At 5 years, only 2 women (6%) with no PR (AP < 0) developed de novo pPOP with OD symptoms; 1 of these underwent subsequent PR. Without PR repair, nearly all participants (23/24; 96%) demonstrated sustained resolution of pPOP, and none underwent PR within 5 years. Obstructed defecation symptoms improved in all groups after ASC with or without PR, although OD symptoms were still present at 5 years, with rates ranging from 17% to 19%. Regardless of concomitant PR, symptomatic pPOP is common 5 years after ASC. Obstructed defecation symptoms may improve after ASC with or without PR. Additional studies are needed to define criteria for performing PR at the time of planned ASC. C1 [Grimes, Cara L.] Columbia Univ, Med Ctr, Dept Obstet & Gynecol, New York, NY 10027 USA. [Lukacz, Emily S.] UC San Diego Hlth Syst, Dept Reprod Med, San Diego, CA USA. [Gantz, Marie G.; Warren, Lauren Klein] RTI Int, Res Triangle Pk, NC USA. [Brubaker, Linda] Loyola Univ, Stritch Sch Med, Dept Obstet & Gynecol, Chicago, IL 60611 USA. [Brubaker, Linda] Loyola Univ, Stritch Sch Med, Dept Urol, Chicago, IL 60611 USA. [Zyczynski, Halina M.] Univ Pittsburgh, Dept Obstet Gynecol & Reprod Sci, Pittsburgh, PA USA. [Richter, Holly E.] Univ Alabama Birmingham, Dept Obstet & Gynecol, Birmingham, AL 35294 USA. [Jelovsek, John Eric] Cleveland Clin, Obstet Gynecol & Womens Hlth Inst, Cleveland, OH 44106 USA. [Cundiff, Geoffrey] Univ British Columbia, Dept Obstet & Gynaecol, Vancouver, BC V5Z 1M9, Canada. [Fine, Paul] Baylor Coll Med, Dept Obstet & Gynecol, Houston, TX 77030 USA. [Visco, Anthony G.] Duke Univ, Med Ctr, Dept Obstet & Gynecol, Durham, NC 27710 USA. [Zhang, Min] Univ Michigan, Dept Biostat, Ann Arbor, MI 48109 USA. [Meikle, Susan] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, NIH, Bethesda, MD USA. RP Grimes, CL (reprint author), Columbia Univ, Med Ctr, Dept Obstet & Gynecol, New York, NY 10027 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 0029-7828 EI 1533-9866 J9 OBSTET GYNECOL SURV JI Obstet. Gynecol. Surv. PD DEC PY 2014 VL 69 IS 12 BP 734 EP 735 DI 10.1097/OGX.0000000000000131 PG 2 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA AW4XM UT WOS:000346280900011 ER PT J AU Alstott, J Panzarasa, P Rubinov, M Bullmore, ET Vertes, PE AF Alstott, Jeff Panzarasa, Pietro Rubinov, Mikail Bullmore, Edward T. Vertes, Petra E. TI A Unifying Framework for Measuring Weighted Rich Clubs SO SCIENTIFIC REPORTS LA English DT Article ID COMMUNITY STRUCTURE; COMPLEX NETWORKS; ORGANIZATION; CONNECTOME; CENTRALITY AB Network analysis can help uncover meaningful regularities in the organization of complex systems. Among these, rich clubs are a functionally important property of a variety of social, technological and biological networks. Rich clubs emerge when nodes that are somehow prominent or 'rich' (e.g., highly connected) interact preferentially with one another. The identification of rich clubs is non-trivial, especially in weighted networks, and to this end multiple distinct metrics have been proposed. Here we describe a unifying framework for detecting rich clubs which intuitively generalizes various metrics into a single integrated method. This generalization rests upon the explicit incorporation of randomized control networks into the measurement process. We apply this framework to real-life examples, and show that, depending on the selection of randomized controls, different kinds of rich-club structures can be detected, such as topological and weighted rich clubs. C1 [Alstott, Jeff; Rubinov, Mikail; Bullmore, Edward T.; Vertes, Petra E.] Univ Cambridge, Dept Psychiat, Behav & Clin Neurosci Inst, Cambridge CB2 0SZ, England. [Alstott, Jeff] NIMH, Sect Crit Brain Dynam, Bethesda, MD 20892 USA. [Panzarasa, Pietro] Queen Mary Univ London, Sch Business & Management, London E1 4NS, England. [Rubinov, Mikail] Univ Cambridge, Churchill Coll, Cambridge CB2 0SZ, England. RP Alstott, J (reprint author), Univ Cambridge, Dept Psychiat, Behav & Clin Neurosci Inst, Cambridge CB2 0SZ, England. EM jja34@cam.ac.uk OI Vertes, Petra E./0000-0002-0992-3210; Bullmore, Edward/0000-0002-8955-8283 FU NIH-Oxford-Cambridge Scholarship Program; NARSAD Young Investigator grant; Isaac Newton Trust grant; Medical Research Council [MR/K020706/1] FX We would like to extend our gratitude to Vittoria Colizza for her comments and suggestions on the development of this paper. We would like to thank Tore Opsahl and Martijn van den Heuvel for making their data easily accessible. J.A. is supported by the NIH-Oxford-Cambridge Scholarship Program. P.P. is employed by Queen Mary University of London. M.R. is supported by the NARSAD Young Investigator and Isaac Newton Trust grants. E.T.B. is employed half-time by the University of Cambridge, UK, and half-time by GlaxoSmithKline (GSK). P.E.V. is supported by the Medical Research Council (grant number MR/K020706/1). NR 28 TC 5 Z9 5 U1 1 U2 5 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 2045-2322 J9 SCI REP-UK JI Sci Rep PD DEC 1 PY 2014 VL 4 AR 7258 DI 10.1038/srep07258 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA AW4NK UT WOS:000346257700006 PM 25435201 ER PT J AU Behar, SM Carpenter, SM Booty, MG Barber, DL Jayaraman, P AF Behar, Samuel M. Carpenter, Stephen M. Booty, Matthew G. Barber, Daniel L. Jayaraman, Pushpa TI Orchestration of pulmonary T cell immunity during Mycobacterium tuberculosis infection: Immunity interruptus SO SEMINARS IN IMMUNOLOGY LA English DT Review DE Tuberculosis; T cell; Priming; Cytokine; Exhaustion; Memory ID CHRONIC VIRAL-INFECTION; NITRIC-OXIDE SYNTHASE; TUMOR-NECROSIS-FACTOR; IFN-GAMMA PRODUCTION; CD8(+) T; ACTIVE TUBERCULOSIS; PROTECTIVE IMMUNITY; IN-VIVO; INTERFERON-GAMMA; LATENT TUBERCULOSIS AB Despite the introduction almost a century ago of Mycobacterium bovis BCG (BCG), an attenuated form of M. bovis that is used as a vaccine against Mycobacterium tuberculosis, tuberculosis remains a global health threat and kills more than 1.5 million people each year. This is mostly because BCG fails to prevent pulmonary disease - the contagious form of tuberculosis. Although there have been significant advances in understanding how the immune system responds to infection, the qualities that define protective immunity against M. tuberculosis remain poorly characterized. The ability to predict who will maintain control over the infection and who will succumb to clinical disease would revolutionize our approach to surveillance, control, and treatment. Here we review the current understanding of pulmonary T cell responses following M. tuberculosis infection. While infection elicits a strong immune response that contains infection, M. tuberculosis evades eradication. Traditionally, its intracellular lifestyle and alteration of macrophage function are viewed as the dominant mechanisms of evasion. Now we appreciate that chronic inflammation leads to T cell dysfunction. While this may arise as the host balances the goals of bacterial sterilization and avoidance of tissue damage, it is becoming clear that T cell dysfunction impairs host resistance. Defining the mechanisms that lead to T cell dysfunction is crucial as memory T cell responses are likely to be subject to the same subject to the same pressures. Thus, success of T cell based vaccines is predicated on memory T cells avoiding exhaustion while at the same time not promoting overt tissue damage. (C) 2014 Elsevier Ltd. All rights reserved. C1 [Behar, Samuel M.; Carpenter, Stephen M.; Booty, Matthew G.; Jayaraman, Pushpa] Univ Massachusetts, Sch Med, Dept Microbiol & Physiol Syst, Worcester, MA 01655 USA. [Carpenter, Stephen M.] Univ Massachusetts, Sch Med, Millennium Program, Grad Sch Biomed Sci, Worcester, MA 01605 USA. [Carpenter, Stephen M.] Univ Massachusetts, Sch Med, Dept Med, Div Infect Dis & Immunol, Worcester, MA 01605 USA. [Carpenter, Stephen M.] Brigham & Womens Hosp, Div Infect Dis, Dept Med, Boston, MA 02115 USA. [Booty, Matthew G.] Harvard Univ, Div Med Sci, Program Immunol, Sch Med, Boston, MA 02115 USA. [Barber, Daniel L.] NIAID, Lymphocyte Biol Unit T, Parasit Dis Lab, NIH, Bethesda, MD 20892 USA. RP Behar, SM (reprint author), Univ Massachusetts, Sch Med, Dept Microbiol & Physiol Syst, Sherman Ctr 8th Floor,55 Lake Ave North, Worcester, MA 01655 USA. EM samuel.behar@umassmed.edu OI Booty, Matthew/0000-0002-0835-3439; Behar, Samuel/0000-0002-3374-6699 FU Intramural Research Program of the NIH/NIAID; NIH [AI106725, AI098637, AI085669, AI100766] FX D.L.B. is supported by the Intramural Research Program of the NIH/NIAID. S.M.B. is supported by the following NIH grants: AI106725, AI098637, AI085669, and AI100766. NR 247 TC 18 Z9 18 U1 1 U2 5 PU ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD PI LONDON PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND SN 1044-5323 J9 SEMIN IMMUNOL JI Semin. Immunol. PD DEC PY 2014 VL 26 IS 6 BP 559 EP 577 DI 10.1016/j.smim.2014.09.003 PG 19 WC Immunology SC Immunology GA AW5RE UT WOS:000346330900013 PM 25311810 ER PT J AU Zeng, XM Hunsberger, JG Simeonov, A Malik, N Pei, Y Rao, M AF Zeng, Xianmin Hunsberger, Joshua G. Simeonov, Anton Malik, Nasir Pei, Ying Rao, Mahendra TI Concise Review: Modeling Central Nervous System Diseases Using Induced Pluripotent Stem Cells SO STEM CELLS TRANSLATIONAL MEDICINE LA English DT Review DE Central nervous system disease; iPSC; Cell-based screening; Genetic engineering ID FATTY-ACID-COMPOSITION; BLOOD-BRAIN-BARRIER; IN-VITRO MODELS; ALZHEIMERS-DISEASE; IPS CELLS; DOCOSAHEXAENOIC ACID; DOPAMINERGIC-NEURONS; DRUG DISCOVERY; SMALL-MOLECULE; RETT-SYNDROME AB Induced pluripotent stem cells (iPSCs) offer an opportunity to delve into the mechanisms underlying development while also affording the potential to take advantage of a number of naturally occurring mutations that contribute to either disease susceptibility or resistance. Just as with any new field, several models of screening are being explored, and innovators are working on the most efficient methods to overcome the inherent limitations of primary cell screens using iPSCs. In the present review, we provide a background regarding why iPSCs represent a paradigm shift for central nervous system (CNS) disease modeling. We describe the efforts in the field to develop more biologically relevant CNS disease models, which should provide screening assays useful for the pharmaceutical industry. We also provide some examples of successful uses for iPSC-based screens and suggest that additional development could revolutionize the field of drug discovery. The development and implementation of these advanced iPSC-based screens will create a more efficient disease-specific process underpinned by the biological mechanism in a patient- and disease-specific manner rather than by trial-and-error. Moreover, with careful and strategic planning, shared resources can be developed that will enable exponential advances in the field. This will undoubtedly lead to more sensitive and accurate screens for early diagnosis and allow the identification of patient-specific therapies, thus, paving the way to personalized medicine. C1 [Zeng, Xianmin] XCell Sci Inc, Novato, CA USA. [Zeng, Xianmin; Pei, Ying] Buck Inst Res Aging, Novato, CA 94945 USA. [Hunsberger, Joshua G.; Malik, Nasir; Rao, Mahendra] Ctr Regenerat Med, Lab Stem Cell Biol, NIH, Bethesda, MD USA. [Simeonov, Anton] Natl Ctr Adv Translat Sci, NIH, Bethesda, MD USA. [Rao, Mahendra] New York Stem Cell Fdn, New York, NY USA. RP Zeng, XM (reprint author), Buck Inst Res Aging, 8001 Redwood Blvd, Novato, CA 94945 USA. EM xzeng@xcellscience.com NR 67 TC 8 Z9 9 U1 2 U2 17 PU ALPHAMED PRESS PI DURHAM PA 318 BLACKWELL ST, STE 260, DURHAM, NC 27701-2884 USA SN 2157-6564 EI 2157-6580 J9 STEM CELL TRANSL MED JI Stem Cells Transl. Med. PD DEC PY 2014 VL 3 IS 12 BP 1418 EP 1428 DI 10.5966/sctm.2014-0102 PG 11 WC Cell & Tissue Engineering SC Cell Biology GA AW7QZ UT WOS:000346460900017 PM 25368377 ER PT J AU Desai, VG Kwekel, JC Vijay, V Moland, CL Herman, EH Lee, T Han, T Lewis, SM Davis, KJ Muskhelishvili, L Kerr, S Fuscoe, JC AF Desai, Varsha G. Kwekel, Joshua C. Vijay, Vikrant Moland, Carrie L. Herman, Eugene H. Lee, Taewon Han, Tao Lewis, Sherry M. Davis, Kelly J. Muskhelishvili, Levan Kerr, Susan Fuscoe, James C. TI Early biomarkers of doxorubicin-induced heart injury in a mouse model SO TOXICOLOGY AND APPLIED PHARMACOLOGY LA English DT Article DE Doxorubicin; Heart; MicroRNA profiling; Biomarker; Mouse ID CARDIAC TROPONIN-T; MYOCARDIAL-INFARCTION; INDUCED CARDIOTOXICITY; CARDIOVASCULAR-DISEASE; INDUCED CARDIOMYOPATHY; MOLECULAR-MECHANISMS; GENE-EXPRESSION; MUSCLE CELLS; MICRORNAS; FAILURE AB Cardiac troponins, which are used as myocardial injury markers, are released in plasma only after tissue damage has occurred. Therefore, there is a need for identification of biomarkers of earlier events in cardiac injury to limit the extent of damage. To accomplish this, expression profiling of 1179 unique microRNAs (miRNAs) was performed in a chronic cardiotoxicity mouse model developed in our laboratory. Male B6C3F(1) mice were injected intravenously with 3 mg/kg doxorubicin (DOX; an anti-cancer drug), or saline once a week for 2, 3, 4, 6, and 8 weeks, resulting in cumulative DOX doses of 6, 9, 12, 18, and 24 mg/kg, respectively. Mice were euthanized a week after the last dose. Cardiac injury was evidenced in mice exposed to 18 mg/kg and higher cumulative DOX dose whereas examination of hearts by light microscopy revealed cardiac lesions at 24 mg/kg DOX. Also, 24 miRNAs were differentially expressed in mouse hearts, with the expression of 1, 1, 2, 8, and 21 miRNAs altered at 6, 9, 12, 18, and 24 mg/kg DOX, respectively. A pro-apoptotic miR-34a was the only miRNA that was upregulated at all cumulative DOX doses and showed a significant dose-related response. Up-regulation of miR-34a at 6 mg/kg DOX may suggest apoptosis as an early molecular change in the hearts of DOX-treated mice. At 12 mg/kg DOX, up-regulation of miR-34a was associated with down-regulation of hypertrophy-related miR-150; changes observed before cardiac injury. These findings may lead to the development of biomarkers of earlier events in DOX-induced cardiotoxicity that occur before the release of cardiac troponins. Published by Elsevier Inc. C1 [Desai, Varsha G.; Kwekel, Joshua C.; Vijay, Vikrant; Moland, Carrie L.; Han, Tao; Fuscoe, James C.] US FDA, Personalized Med Branch, Div Syst Biol, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. [Herman, Eugene H.] NCI, Toxicol & Pharmacol Branch, Dev Therapeut Program, Div Canc Treatment & Diag, Rockville, MD 20850 USA. [Lee, Taewon] Korea Univ, Dept Math, Sejong 339700, Chungnam, South Korea. [Lewis, Sherry M.] US FDA, Off Sci Coordinat, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. [Davis, Kelly J.; Muskhelishvili, Levan] Natl Ctr Toxicol Res, Toxicol Pathol Associates, Jefferson, AR 72079 USA. [Kerr, Susan] Arkansas Heart Hosp, Little Rock, AR 72211 USA. RP Desai, VG (reprint author), US FDA, Personalized Med Branch, Div Syst Biol, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. EM varsha.desai@fda.hhs.gov RI Vijay, Vikrant/E-7651-2010 OI Vijay, Vikrant/0000-0001-8425-1285 NR 63 TC 20 Z9 21 U1 2 U2 13 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0041-008X EI 1096-0333 J9 TOXICOL APPL PHARM JI Toxicol. Appl. Pharmacol. PD DEC 1 PY 2014 VL 281 IS 2 BP 221 EP 229 DI 10.1016/j.taap.2014.10.006 PG 9 WC Pharmacology & Pharmacy; Toxicology SC Pharmacology & Pharmacy; Toxicology GA AW4BR UT WOS:000346227000008 PM 25448438 ER PT J AU Ennis, RC Asico, LD Armando, I Yang, J Feranil, JB Jurgens, JA Escano, CS Yu, PY Wang, XY Sibley, DR Jose, PA Villar, VAM AF Ennis, Riley Charles Asico, Laureano D. Armando, Ines Yang, Jian Feranil, Jun B. Jurgens, Julie A. Escano, Crisanto S., Jr. Yu, Peiying Wang, Xiaoyan Sibley, David R. Jose, Pedro A. Villar, Van Anthony M. TI Dopamine D-1-like receptors regulate the alpha(1A)-adrenergic receptor in human renal proximal tubule cells and D-1-like dopamine receptor knockout mice SO AMERICAN JOURNAL OF PHYSIOLOGY-RENAL PHYSIOLOGY LA English DT Article DE adrenergic receptor; dopamine receptor; knockout mice; renal proximal tubule cells; sodium transport ID ANGIOTENSIN-II TYPE-1; NA-K-ATPASE; EPITHELIAL-CELLS; NA+,K+-ATPASE ACTIVITY; SODIUM-TRANSPORT; ALPHA-1-ADRENERGIC RECEPTOR; BIDIRECTIONAL REGULATION; ADRENERGIC-STIMULATION; CAVEOLAE MICRODOMAINS; INTRARENAL DOPAMINE AB Thehomeostatic control of blood pressure hinges upon the delicate balance between prohypertensinogenic and antihypertensinogenic systems. D-1-like dopamine receptors [dopamine D-1 and D-5 receptors (D(1)Rs and D(5)Rs, respectively)] and the alpha(1A)-adrenergic receptor (alpha(1A)-AR) are expressed in the renal proximal tubule and engender opposing effects on Na+ transport, i.e., natriuresis (via D(1)Rs and D(5)Rs) or antinatriuresis (via alpha(1A)-ARs). We tested the hypothesis that the D1R/D5R regulates the alpha(1A)-AR. D-1-like dopamine receptors coimmunoprecipitated, colocalized, and cofractionated with alpha(1A)-ARs in lipid rafts in immortalized human renal proximal tubule cells. Long-term treatment with the D1R/D5R agonist fenoldopam resulted in decreased D1R and D5R expression but increased alpha(1A)-AR abundance in the plasma membrane. Short-term fenoldopam treatment stimulated the translocation of Na+-K+-ATPase from the plasma membrane to the cytosol that was partially reversed by an alpha(1A)-AR agonist, which by itself induced Na+-K+-ATPase translocation from the cytosol to the plasma membrane. The alpha(1A)-AR-specific agonist A610603 also minimized the ability of fenoldopam to inhibit Na+ K+-ATPase activity. To determine the interaction among D(1)Rs, D(5)Rs, and alpha(1A)-ARs in vivo, we used phenylephrine and A610603 to decrease Na+ excretion in several D1-like dopamine receptor knockout mouse strains. Phenylephrine and A61603 treatment resulted in a partial reduction of urinary Na+ excretion in wild-type mice and its abolition in D1R knockout, D5R knockout, and D1R-D5R double-knockout mice. Our results demonstrate the ability of the D-1-like dopamine receptors to regulate the expression and activity of alpha(1A)-AR. Elucidating the intricacies of the interaction among these receptors is crucial for a better understanding of the crosstalk between anti-and pro-hypertensive systems. C1 [Ennis, Riley Charles] Thomas Jefferson High Sch Sci & Technol, Alexandria, VA USA. [Asico, Laureano D.; Armando, Ines; Yang, Jian; Feranil, Jun B.; Jurgens, Julie A.; Escano, Crisanto S., Jr.; Yu, Peiying; Wang, Xiaoyan; Jose, Pedro A.; Villar, Van Anthony M.] Univ Maryland, Sch Med, Dept Med, Div Nephrol, Baltimore, MD 21201 USA. [Sibley, David R.] NINDS, Mol Neuropharmacol Sect, NIH, Bethesda, MD 20892 USA. [Jose, Pedro A.] Univ Maryland, Sch Med, Dept Physiol, Baltimore, MD 21201 USA. RP Villar, VAM (reprint author), Univ Maryland, Sch Med, 20 Penn St,HSF 2,Suite S003C, Baltimore, MD 21201 USA. EM vvillar@medicine.umaryland.edu FU National Institutes of Health [R01-DK-039308, R01-HL-092196, R37-HL-023081, R01-DK-090918] FX This work was supported, in part, by National Institutes of Health Grants R01-DK-039308, R01-HL-092196, R37-HL-023081, and R01-DK-090918. NR 77 TC 0 Z9 0 U1 0 U2 1 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 1931-857X EI 1522-1466 J9 AM J PHYSIOL-RENAL JI Am. J. Physiol.-Renal Physiol. PD DEC 1 PY 2014 VL 307 IS 11 BP F1238 EP F1248 DI 10.1152/ajprenal.00119.2014 PG 11 WC Physiology; Urology & Nephrology SC Physiology; Urology & Nephrology GA AW0YW UT WOS:000346018200009 PM 25339698 ER PT J AU Tan, FCC Hutchison, ER Eitan, E Mattson, MP AF Tan, Florence C. C. Hutchison, Emmette R. Eitan, Erez Mattson, Mark P. TI Are there roles for brain cell senescence in aging and neurodegenerative disorders? SO BIOGERONTOLOGY LA English DT Review DE Senescence; Neurons; Neurodegeneration; Astrocytes ID DNA-DAMAGE RESPONSE; NEURAL STEM-CELLS; LYSOSOMAL BETA-GALACTOSIDASE; AMYLOID PRECURSOR PROTEIN; SPINAL GANGLION NEURONS; FIBROBLASTS IN-VITRO; N-TERMINAL KINASE; ALZHEIMERS-DISEASE; PARKINSONS-DISEASE; REPLICATIVE SENESCENCE AB The term cellular senescence was introduced more than five decades ago to describe the state of growth arrest observed in aging cells. Since this initial discovery, the phenotypes associated with cellular senescence have expanded beyond growth arrest to include alterations in cellular metabolism, secreted cytokines, epigenetic regulation and protein expression. Recently, senescence has been shown to play an important role in vivo not only in relation to aging, but also during embryonic development. Thus, cellular senescence serves different purposes and comprises a wide range of distinct phenotypes across multiple cell types. Whether all cell types, including post-mitotic neurons, are capable of entering into a senescent state remains unclear. In this review we examine recent data that suggest that cellular senescence plays a role in brain aging and, notably, may not be limited to glia but also neurons. We suggest that there is a high level of similarity between some of the pathological changes that occur in the brain in Alzheimer's and Parkinson's diseases and those phenotypes observed in cellular senescence, leading us to propose that neurons and glia can exhibit hallmarks of senescence previously documented in peripheral tissues. C1 [Tan, Florence C. C.; Hutchison, Emmette R.; Eitan, Erez; Mattson, Mark P.] NIA, Lab Neurosci, Intramural Res Program, Baltimore, MD 21224 USA. RP Hutchison, ER (reprint author), NIA, Lab Neurosci, Intramural Res Program, Baltimore, MD 21224 USA. EM hutchisone@mail.nih.gov; erez.eitan@nih.gov FU Intramural Research Program of the NIH, National Institute on Aging FX This research was supported by the Intramural Research Program of the NIH, National Institute on Aging. NR 190 TC 8 Z9 9 U1 1 U2 18 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1389-5729 EI 1573-6768 J9 BIOGERONTOLOGY JI Biogerontology PD DEC PY 2014 VL 15 IS 6 SI SI BP 643 EP 660 DI 10.1007/s10522-014-9532-1 PG 18 WC Geriatrics & Gerontology SC Geriatrics & Gerontology GA AW3EH UT WOS:000346168100008 PM 25305051 ER PT J AU Roy, AK Benson, BE Degnan, KA Perez-Edgar, K Pine, DS Fox, NA Ernst, M AF Roy, Amy Krain Benson, Brenda E. Degnan, Kathryn A. Perez-Edgar, Koraly Pine, Daniel S. Fox, Nathan A. Ernst, Monique TI Alterations in amygdala functional connectivity reflect early temperament SO BIOLOGICAL PSYCHOLOGY LA English DT Article DE Behavioral inhibition; Functional connectivity; Amygdala; Temperament; Anxiety; fMRI ID GENERALIZED ANXIETY DISORDER; BEHAVIORAL-INHIBITION; ANXIOUS TEMPERAMENT; RISK-FACTOR; CORTEX; ADOLESCENTS; CHILDHOOD; CEREBELLUM; RESPONSES; FACES AB Behavioral inhibition (BI) is a temperament identified early in life that is associated with increased risk for anxiety disorders. Amygdala hyperresponsivity, found both in behaviorally inhibited and anxious individuals, suggests that amygdala dysfunction may represent a marker of anxiety risk. However, broader amygdala networks have not been examined in individuals with a history of childhood BI. This study uses resting state fMRI to assess amygdala intrinsic functional connectivity (iFC) in 38 healthy young adults (19 with a history of BI, 19 with no history of BI) selected from a longitudinal study. Centromedial, basolateral, and superficial amygdala iFCs were compared between groups and examined in relation to self-report measures of anxiety. Group differences were observed in amygdala iFC with prefrontal cortex, striatum, anterior insula, and cerebellum. Adults characterized with BI in childhood endorsed greater state anxiety prior to entering the scanner, which was associated with several of the group differences. Findings support enduring effects of BI on amygdala circuitry, even in the absence of current psychopathology. (C) 2014 Elsevier B.V. All rights reserved. C1 [Roy, Amy Krain] Fordham Univ, Dept Psychol, Bronx, NY 10458 USA. [Benson, Brenda E.; Pine, Daniel S.; Ernst, Monique] NIMH, Sect Dev & Affect Neurosci, Bethesda, MD 20892 USA. [Degnan, Kathryn A.; Fox, Nathan A.] Univ Maryland, Dept Human Dev & Quantitat Methodol, College Pk, MD 20742 USA. [Perez-Edgar, Koraly] Penn State Univ, Dept Psychol, University Pk, PA 16802 USA. RP Roy, AK (reprint author), Fordham Univ, Dept Psychol, 441 East Fordham Rd, Bronx, NY 10458 USA. EM aroy3@fordham.edu OI Perez-Edgar, Koraly/0000-0003-4051-9563 FU National Institute of Mental Health [5U01MH093349-02, 3U01MH093349-02S1, K01-MH073569] FX This research was supported by the National Institute of Mental Health (5U01MH093349-02; 3U01MH093349-02S1 [PI: N.A. Fox]; K01-MH073569 [PI: K. Perez-Edgar]). NR 41 TC 9 Z9 9 U1 5 U2 16 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0301-0511 EI 1873-6246 J9 BIOL PSYCHOL JI Biol. Psychol. PD DEC PY 2014 VL 103 BP 248 EP 254 DI 10.1016/j.biopsycho.2014.09.007 PG 7 WC Psychology, Biological; Behavioral Sciences; Psychology; Psychology, Experimental SC Psychology; Behavioral Sciences GA AW0HF UT WOS:000345971200031 PM 25261727 ER PT J AU Zhu, C Pinsky, P Huang, WY Purdue, M AF Zhu, Claire Pinsky, Paul Huang, Wen-Yi Purdue, Mark TI Laboratory Detective Work Identifies a Mishandling Problem in Sample Aliquoting SO BIOPRESERVATION AND BIOBANKING LA English DT Article ID CANCER SCREENING TRIAL; OVARIAN-CANCER; PROSTATE; LUNG AB Data from a recent ovarian cancer biomarker study using serum aliquots from the Prostate, Lung, Colorectal, and Ovarian (PLCO) Cancer Screening Trial Biorepository showed that CA125II concentrations in these aliquots were significantly lower than those previously measured in the same subjects from the same blood draw. We designed an experiment to investigate whether samples used in the study (reference study) were compromised during the aliquoting process. We measured CA125II in the "sister" vials created during the same aliquoting process as the reference study aliquot, and in "cousin" vials newly aliquoted from another parent vial from the same blood draw, from 15 healthy controls in the study. Because the sister vials were created in a specific order, we also assessed whether there was a CA125II concentration gradient among the sisters. The Wilcoxon signed-rank test was used to test the statistical significance of the observed differences. Mean CA125II concentration (volume-averaged) was greater in the sisters than the cousins in all 15 subjects (p<0.001). The mean coefficient of variation was 0.25 (range: 0.12-0.43) in the sisters and 0.11 (range: 0.-1.1) in the cousins (p<0.008). The mean ratio of CA125II in the 5(th) aliquoted versus the 3(rd) aliquoted sister vial was 1.66 (1.25-2.5, p<0.001). These data suggest that the parent vials were not adequately mixed before they were aliquoted. CA125II in serum can partially precipitate to form a concentration gradient in long-term storage. Rigorous vortexing after thawing and before aliquoting is thus critical. C1 [Zhu, Claire; Pinsky, Paul] NCI, Canc Prevent Div, Bethesda, MD 20892 USA. [Huang, Wen-Yi; Purdue, Mark] NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. RP Zhu, C (reprint author), NCI, Early Detect Res Grp, Canc Prevent Div, 9609 Med Ctr Dr,Room 5E106 MSC 9790, Bethesda, MD 20892 USA. EM zhucla@mail.nih.gov NR 5 TC 0 Z9 0 U1 2 U2 2 PU MARY ANN LIEBERT, INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1947-5535 EI 1947-5543 J9 BIOPRESERV BIOBANK JI Biopreserv. Biobank. PD DEC 1 PY 2014 VL 12 IS 6 BP 430 EP 432 DI 10.1089/bio.2014.0046 PG 3 WC Cell Biology; Chemistry, Applied; Medical Laboratory Technology SC Cell Biology; Chemistry; Medical Laboratory Technology GA AW5SY UT WOS:000346335300012 PM 25496156 ER PT J AU Modi, HR Basselin, M Rapoport, SI AF Modi, Hiren R. Basselin, Mireille Rapoport, Stanley I. TI Valnoctamide, a non-teratogenic amide derivative of valproic acid, inhibits arachidonic acid activation in vitro by recombinant acyl-CoA synthetase-4 SO BIPOLAR DISORDERS LA English DT Article DE acyl-CoA synthetase 4; anticonvulsant; arachidonic acid; bipolar disorder; brain; cascade; enzyme; inhibition; metabolism; Michaelis-Menten kinetics; mood stabilizer; rat; valnoctamide; valproate ID STEREOSELECTIVE PHARMACOKINETIC ANALYSIS; BIPOLAR DISORDER; HEALTHY-SUBJECTS; LIGASE 4; BRAIN; ISOMER; DRUG; RATS; ANTICONVULSANT; EXPRESSION AB ObjectiveValproic acid (VPA), a mood stabilizer used for treating bipolar disorder (BD), uncompetitively inhibits acylation of arachidonic acid (AA) by recombinant AA-selective acyl-CoA synthetase 4 (Acsl4) at an enzyme inhibition constant (K-i) of 25mM. Inhibition may account for VPA's ability to reduce AA turnover in brain phospholipids of unanesthetized rats and to be therapeutic in BD. However, VPA is teratogenic. We tested whether valnoctamide (VCD), a non-teratogenic amide derivative of a VPA chiral isomer, which had antimanic potency in a phase III BD trial, also inhibits recombinant Acsl4. MethodsRat Acsl4-flag protein was expressed in Escherichia coli. We used Michaelis-Menten kinetics to characterize and quantify the ability of VCD to inhibit conversion of AA to AA-CoA by recombinant Acsl4 in vitro. ResultsAcsl4-mediated activation of AA to AA-CoA by Acsl4 was inhibited uncompetitively by VCD, with a K-i of 6.38mM. ConclusionsVCD's ability to uncompetitively inhibit AA activation to AA-CoA by Acsl4, at a lower K-i than VPA, suggests that, like VPA, VCD may reduce AA turnover in rat brain phospholipids. If so, VCD and other non-teratogenic Acsl4 inhibitors might be considered further for treating BD. C1 [Modi, Hiren R.; Basselin, Mireille; Rapoport, Stanley I.] NIA, Brain Physiol & Metab Sect, Lab Neurosci, NIH, Bethesda, MD 20892 USA. RP Modi, HR (reprint author), NIA, Brain Physiol & Metab Sect, Lab Neurosci, NIH, 9000 Rockville Pike Bldg 9,Room 1S126, Bethesda, MD 20892 USA. EM hirumodi@gmail.com FU Intramural Research Program of the National Institute on Aging, National Institute of Health FX This work was supported by the Intramural Research Program of the National Institute on Aging, National Institute of Health. We thank the Chemical Synthesis and Drug Supply Program of the National Institute of Mental Health (Research Triangle Park, NC, USA) for supplying us with valnoctamide. NR 39 TC 1 Z9 1 U1 3 U2 4 PU WILEY PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1398-5647 EI 1399-5618 J9 BIPOLAR DISORD JI Bipolar Disord. PD DEC PY 2014 VL 16 IS 8 BP 875 EP 880 DI 10.1111/bdi.12220 PG 6 WC Clinical Neurology; Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA AW0KK UT WOS:000345980900010 PM 25041123 ER PT J AU Fuhrman, BJ Xu, X Falk, RT Dallal, CM Veenstra, TD Keefer, LK Graubard, BI Brinton, LA Ziegler, RG Gierach, GL AF Fuhrman, Barbara J. Xu, Xia Falk, Roni T. Dallal, Cher M. Veenstra, Timothy D. Keefer, Larry K. Graubard, Barry I. Brinton, Louise A. Ziegler, Regina G. Gierach, Gretchen L. TI Assay Reproducibility and Interindividual Variation for 15 Serum Estrogens and Estrogen Metabolites Measured by Liquid Chromatography-Tandem Mass Spectrometry SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Article ID BREAST-CANCER RISK; POSTMENOPAUSAL WOMEN; URINARY ESTROGENS; HORMONE-LEVELS; ESTRADIOL AB Background: Interindividual differences in estrogen metabolism may partially account for differences in risks of estrogen-responsive cancers. Weconducted a proof-of-performance study to assess the reproducibility of a LC/MS-MS method for measurement of 15 serum estrogens and metabolites (all 15 termed EM) in total (conjugated+unconjugated) and unconjugated forms and describe interindividual variation. Methods: Interindividual variation in serum EM profiles was evaluated for 20 premenopausal women, 15 postmenopausal women, and 10 men. Replicate aliquots from 10 premenopausal women, 5 postmenopausal women, and 5 men were assayed eight times over 4 weeks. Components of variance were used to calculate coefficients of variation (CV) and intraclass correlation coefficients (ICC). Results: In postmenopausal women and men, median EM concentrations were similar and substantially lower than that in premenopausal women. Within each sex/menopausal group, the sum of all EM varied 5- to 7-fold across extreme deciles. Some EM had greater variation; total estrone varied approximately 12-fold in premenopausal and postmenopausal women. Unconjugated estradiol varied 17-fold in postmenopausal women but only 5- fold in premenopausal women and men. CVs reflecting variation across replicate measures for individuals were <5% for most EM, but higher in some individuals with a low EM concentration. Overall laboratory CVs for all but one EM were <2% and ICCs were >99% for all EM in each group. Conclusions: The serum EM assay has excellent laboratory reproducibility. In premenopausal women, postmenopausal women, and men, interindividual variation in EM measures is substantially greater than laboratory variation. Impact: The serum EM assay is suitable for epidemiologic application. (C) 2014 AACR. C1 [Fuhrman, Barbara J.; Falk, Roni T.; Dallal, Cher M.; Graubard, Barry I.; Brinton, Louise A.; Ziegler, Regina G.; Gierach, Gretchen L.] NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. [Xu, Xia; Veenstra, Timothy D.] Leidos Biomed Res Inc, Lab Analyt Technol, Canc Res Technol Program, Frederick Natl Lab Canc Res, Frederick, MD USA. [Keefer, Larry K.] NCI, Biol Chem Lab, Ctr Canc Res, Frederick, MD 21701 USA. RP Fuhrman, BJ (reprint author), Univ Arkansas Med Sci, Fay Boozman Coll Publ Hlth, Dept Epidemiol, 4301 W Markham St 820, Little Rock, AR 72205 USA. EM bjfuhrman@uams.edu RI Keefer, Larry/N-3247-2014; Brinton, Louise/G-7486-2015; Gierach, Gretchen/E-1817-2016; OI Keefer, Larry/0000-0001-7489-9555; Brinton, Louise/0000-0003-3853-8562; Gierach, Gretchen/0000-0002-0165-5522; Fuhrman, Barbara/0000-0002-1777-9888 FU Intramural Research Program of the Division of Cancer Epidemiology and Genetics of the National Cancer Institute; National Cancer Institute federal funds [HHSN261200800001E] FX This work was supported by the Intramural Research Program of the Division of Cancer Epidemiology and Genetics of the National Cancer Institute and National Cancer Institute federal funds awarded under Contract HHSN261200800001E to SAIC-Frederick, Inc. NR 18 TC 11 Z9 11 U1 0 U2 7 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1055-9965 EI 1538-7755 J9 CANCER EPIDEM BIOMAR JI Cancer Epidemiol. Biomarkers Prev. PD DEC PY 2014 VL 23 IS 12 BP 2649 EP 2657 DI 10.1158/1055-9965.EPI-14-0438 PG 9 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA AW0FU UT WOS:000345967300005 PM 25472673 ER PT J AU Altekruse, SF Rosenfeld, GE Carrick, DM Pressman, EJ Schully, SD Mechanic, LE Cronin, KA Hernandez, BY Lynch, CF Cozen, W Khoury, MJ Penberthy, LT AF Altekruse, Sean F. Rosenfeld, Gabriel E. Carrick, Danielle M. Pressman, Emilee J. Schully, Sheri D. Mechanic, Leah E. Cronin, Kathleen A. Hernandez, Brenda Y. Lynch, Charles F. Cozen, Wendy Khoury, Muin J. Penberthy, Lynne T. TI SEER Cancer Registry Biospecimen Research: Yesterday and Tomorrow SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Article ID PARAFFIN-EMBEDDED TISSUES; EPITHELIAL HISTOPATHOLOGIC MARKERS; HUMAN-PAPILLOMAVIRUS TYPES; PRE-RITUXIMAB ERA; B-CELL LYMPHOMA; UNITED-STATES; PROTEIN EXPRESSION; COLORECTAL-CANCER; VACCINE INTRODUCTION; DNA METHYLATION AB The National Cancer Institute's (NCI) Surveillance, Epidemiology, and End Results (SEER) registries have been a source of biospecimens for cancer research for decades. Recently, registry-based biospecimen studies have become more practical, with the expansion of electronic networks for pathology and medical record reporting. Formalin-fixed paraffin-embedded specimens are now used for next-generation sequencing and other molecular techniques. These developments create new opportunities for SEER biospecimen research. We evaluated 31 research articles published during 2005 to 2013 based on authors' confirmation that these studies involved linkage of SEER data to biospecimens. Rather than providing an exhaustive review of all possible articles, our intent was to indicate the breadth of research made possible by such a resource. We also summarize responses to a 2012 questionnaire that was broadly distributed to the NCI intra- and extramural biospecimen research community. This included responses from 30 investigators who had used SEER biospecimens in their research. The survey was not intended to be a systematic sample, but instead to provide anecdotal insight on strengths, limitations, and the future of SEER biospecimen research. Identified strengths of this research resource include biospecimen availability, cost, and annotation of data, including demographic information, stage, and survival. Shortcomings include limited annotation of clinical attributes such as detailed chemotherapy history and recurrence, and timeliness of turnaround following biospecimen requests. A review of selected SEER biospecimen articles, investigator feedback, and technological advances reinforced our view that SEER biospecimen resources should be developed. This would advance cancer biology, etiology, and personalized therapy research. (C) 2014 AACR. C1 [Altekruse, Sean F.; Rosenfeld, Gabriel E.; Carrick, Danielle M.; Pressman, Emilee J.; Schully, Sheri D.; Mechanic, Leah E.; Cronin, Kathleen A.; Khoury, Muin J.; Penberthy, Lynne T.] NCI, Div Canc Control & Populat Sci, NIH, Rockville, MD 20850 USA. [Hernandez, Brenda Y.] Univ Hawaii, Ctr Canc, Honolulu, HI 96822 USA. [Lynch, Charles F.] Univ Iowa, Dept Epidemiol, Coll Publ Hlth, Iowa City, IA USA. [Cozen, Wendy] Univ So Calif, Dept Prevent Med, Keck Sch Med, USC Norris Comprehens Canc Ctr, Los Angeles, CA USA. [Cozen, Wendy] Univ So Calif, Dept Pathol, Keck Sch Med, USC Norris Comprehens Canc Ctr, Los Angeles, CA USA. [Khoury, Muin J.] Ctr Dis Control & Prevent, Off Publ Hlth Gen, Atlanta, GA USA. RP Altekruse, SF (reprint author), NCI, Div Canc Control & Populat Sci, 9609 Med Ctr Dr,Room 4E536, Rockville, MD 20850 USA. EM altekrusesf@mail.nih.gov FU Intramural NIH HHS [Z99 CA999999] NR 46 TC 3 Z9 3 U1 1 U2 4 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1055-9965 EI 1538-7755 J9 CANCER EPIDEM BIOMAR JI Cancer Epidemiol. Biomarkers Prev. PD DEC PY 2014 VL 23 IS 12 BP 2681 EP 2687 DI 10.1158/1055-9965.EPI-14-0490 PG 7 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA AW0FU UT WOS:000345967300009 PM 25472677 ER PT J AU Khodr, ZG Sherman, ME Pfeiffer, RM Gierach, GL Brinton, LA Falk, RT Patel, DA Linville, LM Papathomas, D Clare, SE Visscher, DW Mies, C Hewitt, SM Storniolo, AMV Rosebrock, A Caban, JJ Figueroa, JD AF Khodr, Zeina G. Sherman, Mark E. Pfeiffer, Ruth M. Gierach, Gretchen L. Brinton, Louise A. Falk, Roni T. Patel, Deesha A. Linville, Laura M. Papathomas, Daphne Clare, Susan E. Visscher, Daniel W. Mies, Carolyn Hewitt, Stephen M. Storniolo, Anna Maria V. Rosebrock, Adrian Caban, Jesus J. Figueroa, Jonine D. TI Circulating Sex Hormones and Terminal Duct Lobular Unit Involution of the Normal Breast SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Article ID PLASMA PROLACTIN CONCENTRATIONS; CANCER RISK; POSTMENOPAUSAL WOMEN; PREMENOPAUSAL WOMEN; EPIC COHORT; SERUM; PROGESTERONE; TESTOSTERONE; ESTROGEN; AGE AB Background: Terminal duct lobular units (TDLU) are the predominant source of breast cancers. Lesser degrees of age-related TDLU involution have been associated with increased breast cancer risk, but factors that influence involution are largely unknown. We assessed whether circulating hormones, implicated in breast cancer risk, are associated with levels of TDLU involution using data from the Susan G. Komen Tissue Bank (KTB) at the Indiana University Simon Cancer Center (2009-2011). Methods: Weevaluated three highly reproducible measures of TDLU involution, using normal breast tissue samples from the KTB (n = 390): TDLU counts, median TDLU span, and median acini counts per TDLU. RRs (for continuous measures), ORs (for categorical measures), 95% confidence intervals (95% CI), and P-trends were calculated to assess the association between tertiles of estradiol, testosterone, sex hormone-binding globulin (SHBG), progesterone, and prolactin with TDLU measures. All models were stratified by menopausal status and adjusted for confounders. Results: Among premenopausal women, higher prolactin levels were associated with higher TDLU counts (RRT3vsT1:1.18; 95% CI: 1.07-1.31; P-trend = 0.0005), but higher progesterone was associated with lower TDLU counts (RRT3vsT1:0.80; 95% CI: 0.72-0.89; P-trend < 0.0001). Among postmenopausal women, higher levels of estradiol (RRT3vsT1:1.61; 95% CI: 1.32-1.97; P-trend < 0.0001) and testosterone (RRT3vsT1: 1.32; 95% CI: 1.09-1.59; P-trend = 0.0043) were associated with higher TDLU counts. Conclusions: These data suggest that select hormones may influence breast cancer risk potentially through delaying TDLU involution. Impact: Increased understanding of the relationship between circulating markers and TDLU involution may offer new insights into breast carcinogenesis. (C) 2014 AACR. C1 [Khodr, Zeina G.; Sherman, Mark E.; Pfeiffer, Ruth M.; Gierach, Gretchen L.; Brinton, Louise A.; Falk, Roni T.; Patel, Deesha A.; Papathomas, Daphne; Figueroa, Jonine D.] NCI, Div Canc Epidemiol & Genet, Dept Hlth & Human Serv, Bethesda, MD 20892 USA. [Sherman, Mark E.] NCI, Canc Prevent Div, Dept Hlth & Human Serv, Bethesda, MD 20892 USA. [Linville, Laura M.] George Washington Univ, Sch Med & Hlth Sci, Washington, DC 20052 USA. [Clare, Susan E.] Northwestern Univ, Dept Surg, Feinberg Sch Med, Chicago, IL 60611 USA. [Visscher, Daniel W.] Mayo Clin, Dept Lab Med & Pathol, Rochester, MN USA. [Mies, Carolyn] Univ Penn, Dept Pathol & Lab Med, Philadelphia, PA 19104 USA. [Hewitt, Stephen M.] NCI, Appl Mol Pathol Lab, Pathol Lab, Ctr Canc Res, Bethesda, MD 20892 USA. [Storniolo, Anna Maria V.] Indiana Univ, Susan G Komen Tissue Bank, Simon Canc Ctr, Indianapolis, IN 46204 USA. [Rosebrock, Adrian] Univ Maryland, Dept Comp Sci & Elect Engn, Baltimore, MD 21201 USA. [Caban, Jesus J.] Walter Reed Natl Mil Med Ctr, Natl Intrepid Ctr Excellence, Bethesda, MD USA. RP Figueroa, JD (reprint author), NCI, 9609 Med Ctr Dr,7E-122,MSC 9774, Bethesda, MD 20892 USA. EM FigueroaJ@mail.nih.gov RI Brinton, Louise/G-7486-2015; Gierach, Gretchen/E-1817-2016; OI Brinton, Louise/0000-0003-3853-8562; Gierach, Gretchen/0000-0002-0165-5522; Hewitt, Stephen/0000-0001-8283-1788 FU Division of Cancer Epidemiology and Genetics at the National Cancer Institute; Breast Cancer Research Foundation, Oracle Giving; Catherine Peachey Fund, Inc.; National Cancer Institute, Intramural Research Program; Susan G. Komen FX This study was supported by intramural funds from the Division of Cancer Epidemiology and Genetics at the National Cancer Institute. S. Clare and A. Storniolo are supported by Susan G. Komen, the Breast Cancer Research Foundation, Oracle Giving, and the Catherine Peachey Fund, Inc. Z. Khodr, M. Sherman, R. Pfeiffer, G. Gierach, L. Brinton, R. Falk, D. Patel, L. Linvile, D. Papathomas, S. Hewitt, and J. Figueroa are supported by funds from the National Cancer Institute, Intramural Research Program. NR 53 TC 8 Z9 8 U1 1 U2 3 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1055-9965 EI 1538-7755 J9 CANCER EPIDEM BIOMAR JI Cancer Epidemiol. Biomarkers Prev. PD DEC PY 2014 VL 23 IS 12 BP 2765 EP 2773 DI 10.1158/1055-9965.EPI-14-0667 PG 9 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA AW0FU UT WOS:000345967300018 PM 25472681 ER PT J AU Sun, XZ Sandhu, R Figueroa, JD Gierach, GL Sherman, ME Troester, MA AF Sun, Xuezheng Sandhu, Rupninder Figueroa, Jonine D. Gierach, Gretchen L. Sherman, Mark E. Troester, Melissa A. TI Benign Breast Tissue Composition in Breast Cancer Patients: Association with Risk Factors, Clinical Variables, and Gene Expression SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Article ID MAMMARY-GLAND DEVELOPMENT; TUMOR-STROMA RATIO; MAMMOGRAPHIC DENSITY; PROGNOSTIC-SIGNIFICANCE; BASAL-LIKE; MICROENVIRONMENT; PROGRESSION; INVOLUTION; PATTERNS; SUBTYPES AB Background: Breast tissue composition (epithelium, non-fatty stroma, and adipose) changes qualitatively and quantitatively throughout the lifespan, and may mediate relationships between risk factors and breast cancer initiation. We sought to identify relationships between tissue composition, risk factors, tumor characteristics, and gene expression. Methods: Participants were 146 patients from the Polish Breast Cancer Study, with data on risk factor and clinicopathological characteristics. Benign breast tissue composition was evaluated using digital image analysis of histologic sections. Whole-genome microarrays were performed on the same tissue blocks. Results: Mean epithelial, non-fatty stromal, and adipose proportions were 8.4% (SD = 4.9%), 27.7% (SD = 24.0%), and 64.0% (SD = 24.0%), respectively. Among women <50 years old, stroma proportion decreased and adipose proportion increased with age, with approximately 2% difference per year (P < 0.01). The variation in epithelial proportion with age was modest (0.1% per year). Higher epithelial proportion was associated with obesity (7.6% in nonobese vs. 10.1% in obese; P = 0.02) and with poorly differentiated tumors (7.8% in well/moderate vs. 9.9% in poor; P = 0.05). Gene expression signatures associated with epithelial and stromal proportion were identified and validated. Stroma-associated genes were in metabolism and stem cell maintenance pathways, whereas epithelial genes were enriched for cytokine and immune response pathways. Conclusions: Breast tissue composition was associated with age, body mass index, and tumor grade, with consequences for breast gene expression. Impact: Breast tissue morphologic factors may influence breast cancer etiology. Composition and gene expression may act as biomarkers of breast cancer risk and progression. (C) 2014 AACR. C1 [Sun, Xuezheng; Troester, Melissa A.] Univ N Carolina, Dept Epidemiol, Chapel Hill, NC 27599 USA. [Sandhu, Rupninder; Troester, Melissa A.] Univ N Carolina, Lineberger Comprehens Canc Ctr, Chapel Hill, NC 27599 USA. [Figueroa, Jonine D.; Gierach, Gretchen L.; Sherman, Mark E.] NCI, Hormonal & Reprod Epidemiol Branch, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. [Sherman, Mark E.] NCI, Breast & Gynecol Canc Res Grp, Canc Prevent Div, Bethesda, MD 20892 USA. RP Troester, MA (reprint author), Univ N Carolina, Dept Epidemiol, CB 7435, Chapel Hill, NC 27599 USA. EM troester@unc.edu RI Gierach, Gretchen/E-1817-2016 OI Gierach, Gretchen/0000-0002-0165-5522 FU National Cancer Institute [U01-ES019472, R01-CA138255]; Breast SPORE Project [P50CA058223]; Avon Foundation; Intramural Research Program of the NIH, National Cancer Institute FX This work was supported by grants from the National Cancer Institute (U01-ES019472 and R01-CA138255 to M.A. Troester), a Breast SPORE Project (grant P50CA058223, H.S. Earp PI), and a grant from the Avon Foundation (to M.A. Troester). This work was supported (in part) by the Intramural Research Program of the NIH, National Cancer Institute. NR 43 TC 5 Z9 5 U1 0 U2 5 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1055-9965 EI 1538-7755 J9 CANCER EPIDEM BIOMAR JI Cancer Epidemiol. Biomarkers Prev. PD DEC PY 2014 VL 23 IS 12 BP 2810 EP 2818 DI 10.1158/1055-9965.EPI-14-0507 PG 9 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA AW0FU UT WOS:000345967300022 PM 25249325 ER PT J AU Kitahara, CM Trabert, B Katki, HA Chaturvedi, AK Kemp, TJ Pinto, LA Moore, SC Purdue, MP Wentzensen, N Hildesheim, A Shiels, MS AF Kitahara, Cari M. Trabert, Britton Katki, Hormuzd A. Chaturvedi, Anil K. Kemp, Troy J. Pinto, Ligia A. Moore, Steven C. Purdue, Mark P. Wentzensen, Nicolas Hildesheim, Allan Shiels, Meredith S. TI Body Mass Index, Physical Activity, and Serum Markers of Inflammation, Immunity, and Insulin Resistance SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Article ID C-REACTIVE PROTEIN; ENDOMETRIAL CANCER-RISK; ADIPOSE-TISSUE; BREAST-CANCER; OBESITY; WOMEN; COHORT; MECHANISMS; BIOMARKERS; LEPTIN AB Background: Epidemiologic studies examining circulating levels of inflammatory markers in relation to obesity and physical inactivity may aid in our understanding of the role of inflammation in obesity-related cancers. However, previous studies on this topic have focused on a limited set of markers. Methods: We evaluated associations between body mass index (BMI) and vigorous physical activity level, based on self-report, and serum levels of 78 inflammation-related markers. Markers were measured using a bead-based multiplex method among 1,703 men and women, ages 55-74 years, and with no prior history of cancer at blood draw, and selected for case-control studies nested within the Prostate, Lung, Ovarian, and Colorectal Cancer Screening Trial. Analyses were adjusted for age, sex, smoking, case-control study, physical activity, and BMI. Results: Twelve markers were positively associated with BMI after FDR correction. ORs and 95% confidence interval (CI) for highest versus lowest levels of CCL2/MCP-1, CXCL5/ENA-78, sTNFRII, CXCL10/IP-10, CXCL6/GCP2, CCL13/MCP-4, amylin, CRP, C-peptide, CCL19/MIP-3b, insulin, and leptin were: 1.50 (1.14-1.98), 1.52 (1.12-2.05), 1.61 (1.17-2.20), 1.69 (1.25-2.28), 1.74 (1.24-2.44), 1.75 (1.22-2.50), 1.91 (1.31-2.78), 2.41 (1.36-4.25), 2.78 (1.83-4.24), 3.30 (2.28-4.78), 4.05 (2.51-6.55), and 50.03 (19.87-125.99) per 5 kg/m(2), respectively. Only CXCL12/SDF-1a was associated with physical activity (>= 3 vs. <1 h/wk; OR, 3.28; 95% CI, 1.55-6.94) after FDR correction. Conclusions: BMI was associated with a wide range of circulating markers involved in the inflammatory response. Impact: This cross-sectional analysis identified serum markers could be considered in future studies aimed at understanding the underlying mechanisms linking inflammation with obesity and obesity-related cancers. (C) 2014 AACR. C1 [Kitahara, Cari M.; Trabert, Britton; Katki, Hormuzd A.; Chaturvedi, Anil K.; Moore, Steven C.; Purdue, Mark P.; Wentzensen, Nicolas; Hildesheim, Allan; Shiels, Meredith S.] NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. [Kemp, Troy J.; Pinto, Ligia A.] Leidos Biomed Res Inc, Frederick Natl Lab Canc Res, HPV Immunol Lab, Frederick, MD USA. RP Kitahara, CM (reprint author), Div Canc Epidemiol & Genet, 9609 Med Ctr Dr,Room 7E 566, Bethesda, MD 20892 USA. EM meinholdc@mail.nih.gov RI Katki, Hormuzd/B-4003-2015; Hildesheim, Allan/B-9760-2015; Purdue, Mark/C-9228-2016; Trabert, Britton/F-8051-2015; Moore, Steven/D-8760-2016; Chaturvedi, Anil/J-2024-2015; Kitahara, Cari/R-8267-2016 OI Hildesheim, Allan/0000-0003-0257-2363; Purdue, Mark/0000-0003-1177-3108; Moore, Steven/0000-0002-8169-1661; Chaturvedi, Anil/0000-0003-2696-8899; FU Intramural Research Program of the National Cancer Institute, NIH, Bethesda, Maryland FX This work was supported in part by the Intramural Research Program of the National Cancer Institute, NIH, Bethesda, Maryland. NR 34 TC 19 Z9 19 U1 0 U2 13 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1055-9965 EI 1538-7755 J9 CANCER EPIDEM BIOMAR JI Cancer Epidemiol. Biomarkers Prev. PD DEC PY 2014 VL 23 IS 12 BP 2840 EP 2849 DI 10.1158/1055-9965.EPI-14-0699-T PG 10 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA AW0FU UT WOS:000345967300025 PM 25249326 ER PT J AU Cui, Y Shu, XO Gao, YT Cai, QY Ji, BT Li, HL Rothman, N Wu, J Yang, G Xiang, YB Zheng, W AF Cui, Yong Shu, Xiao-Ou Gao, Yu-Tang Cai, Qiuyin Ji, Bu-Tian Li, Hong-Lan Rothman, Nathaniel Wu, Jie Yang, Gong Xiang, Yong-Bing Zheng, Wei TI Urinary Prostaglandin E-2 Metabolite and Breast Cancer Risk SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Article ID CARCINOMA IN-SITU; ELEVATED AROMATASE EXPRESSION; CYCLOOXYGENASE-2 EXPRESSION; ASPIRIN USE; INFLAMMATION; OBESITY; TUMORIGENESIS; METAANALYSIS; ASSOCIATION; INHIBITORS AB Background: Levels of the cyclooxygenase 2 (COX2) enzyme are elevated in breast cancer tissue, and most COX2 effects are believed to be mediated through overproduction of prostaglandin E2 (PGE2). We evaluated associations between the primary urinary metabolite of PGE2 (PGE-M) and breast cancer risk. Methods: A nested case-control study of 504 cases and 1,082 controls was conducted using data from the Shanghai Women's Health Study, a large population-based prospective cohort study of 74,941 Chinese women. Urinary PGE-M was measured using a liquid chromatography/tandem mass spectrometric method. Logistic regression estimated odds ratios (OR) and 95% confidence intervals (95% CI) with adjustment for potential confounders. Results: Overall, no association between urinary PGE-M and breast cancer was detected. However, a suggestive positive association was found among postmenopausal women. In particular, a clear dose-response relationship between urinary PGE-M and breast cancer was observed among postmenopausal women with a body mass index (BMI) < 25 kg/m(2) (P-linear trend = 0.005). Among these women, risk of breast cancer increased from 1.00 (reference) to 1.06 (95% CI, 0.56-1.99), 1.50 (95% CI, 0.79-2.83), and 2.32 (95% CI, 1.24-4.41) for the lowest to highest quartiles of PGE-M, and such associations were stronger among those who were diagnosed with cancer within the first four years of sample collection. No apparent association was observed among overweight postmenopausal women (BMI >= 25 kg/m(2)). Conclusion: High urinary PGE-M level was associated with elevated risk of breast cancer among normal weight, postmenopausal women. Impact: Urinary PGE-M level may be useful for breast cancer risk assessment among normal weight, postmenopausal women. (C) 2014 AACR. C1 [Cui, Yong; Shu, Xiao-Ou; Cai, Qiuyin; Wu, Jie; Yang, Gong; Zheng, Wei] Vanderbilt Univ, Vanderbilt Epidemiol Ctr, Vanderbilt Ingram Canc Ctr, Sch Med,Dept Med,Div Epidemiol, Nashville, TN 37203 USA. [Gao, Yu-Tang; Li, Hong-Lan; Xiang, Yong-Bing] Shanghai Jiao Tong Univ, Renji Hosp, Sch Med, Shanghai Canc Inst,Dept Epidemiol, Shanghai 200030, Peoples R China. [Ji, Bu-Tian; Rothman, Nathaniel] NCI, Div Canc Epidemiol & Genet, NIH, Rockville, MD USA. [Gao, Yu-Tang; Li, Hong-Lan; Xiang, Yong-Bing] Shanghai Canc Inst, Dept Epidemiol, Shanghai, Peoples R China. RP Zheng, W (reprint author), Vanderbilt Univ, Vanderbilt Epidemiol Ctr, Sch Med, 2525 West End Ave,8th Floor, Nashville, TN 37203 USA. EM wei.zheng@vanderbilt.edu FU U.S. NIH [R37 CA070867] FX This study was supported by grant number R37 CA070867 (to W. Zheng) from the U.S. NIH. NR 38 TC 7 Z9 7 U1 0 U2 6 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1055-9965 EI 1538-7755 J9 CANCER EPIDEM BIOMAR JI Cancer Epidemiol. Biomarkers Prev. PD DEC PY 2014 VL 23 IS 12 BP 2866 EP 2873 DI 10.1158/1055-9965.EPI-14-0685 PG 8 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA AW0FU UT WOS:000345967300028 PM 25214156 ER PT J AU Tasevska, N Midthune, D Tinker, LF Potischman, N Lampe, JW Neuhouser, ML Beasley, JM van Horn, L Prentice, RL Kipnis, V AF Tasevska, Natasha Midthune, Douglas Tinker, Lesley F. Potischman, Nancy Lampe, Johanna W. Neuhouser, Marian L. Beasley, Jeannette M. van Horn, Linda Prentice, Ross L. Kipnis, Victor TI Use of a Urinary Sugars Biomarker to Assess Measurement Error in Self-Reported Sugars Intake in the Nutrition and Physical Activity Assessment Study (NPAAS) SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Article ID FOOD FREQUENCY QUESTIONNAIRE; DOUBLY LABELED WATER; RECOVERY BIOMARKERS; ENERGY-EXPENDITURE; EPIDEMIOLOGIC ASSESSMENT; CALIBRATION EQUATIONS; OBSERVING PROTEIN; HEALTH; CONSUMPTION; RELIABILITY AB Background: Measurement error in self- reported sugars intake may be obscuring the association between sugars and cancer risk in nutritional epidemiologic studies. Methods: We used 24-hour urinary sucrose and fructose as a predictive biomarker for total sugars, to assess measurement error in self-reported sugars intake. The Nutrition and Physical Activity Assessment Study (NPAAS) is a biomarker study within the Women's Health Initiative (WHI) Observational Study that includes 450 postmenopausal women ages 60 to 91 years. Food Frequency Questionnaires (FFQ), four-day food records (4DFR), and three 24-hour dietaryrecalls (24HRs) were collected along with sugars and energy dietary biomarkers. Results: Using the biomarker, we found self-reported sugars to be substantially and roughly equally misreported across the FFQ, 4DFR, and 24HR. All instruments were associated with considerable intake-and person-specific bias. Three 24HRs would provide the least attenuated risk estimate for sugars (attenuation factor, AF = 0.57), followed by FFQ (AF = 0.48) and 4DFR (AF = 0.32), in studies of energy-adjusted sugars and disease risk. In calibration models, self-reports explained little variation in true intake (5%-6% for absolute sugars and 7%-18% for sugars density). Adding participants' characteristics somewhat improved the percentage variation explained (16%-18% for absolute sugars and 29%-40% for sugars density). Conclusions: None of the self-report instruments provided a good estimate of sugars intake, although overall 24HRs seemed to perform the best. Impact: Assuming the calibrated sugars biomarker is unbiased, this analysis suggests that measuring the biomarker in a subsample of the study population for calibration purposes may be necessary for obtaining unbiased risk estimates in cancer association studies. (C) 2014 AACR. C1 [Tasevska, Natasha; Midthune, Douglas; Potischman, Nancy; Kipnis, Victor] NCI, Bethesda, MD 20892 USA. [Tasevska, Natasha] Arizona State Univ, Sch Nutr & Hlth Promot, Phoenix, AZ 85004 USA. [Tinker, Lesley F.; Lampe, Johanna W.; Neuhouser, Marian L.; Prentice, Ross L.] Fred Hutchinson Canc Res Ctr, Div Publ Hlth Sci, Seattle, WA 98104 USA. [Beasley, Jeannette M.] Albert Einstein Coll Med, Dept Epidemiol & Populat Sci, Bronx, NY 10467 USA. [van Horn, Linda] Northwestern Univ, Dept Prevent Med, Chicago, IL 60611 USA. RP Tasevska, N (reprint author), Arizona State Univ, Sch Nutr & Hlth Promot, 500 North 3rd St, Phoenix, AZ 85004 USA. EM natasha.tasevska@asu.edu OI Beasley, Jeannette/0000-0002-9343-6895 FU Intramural Research Program of the National Cancer Institute, NIH; National Cancer Institute [R01 CA119171-04A1]; National Heart, Lung, and Blood Institute, NIH; U.S. Department of Health and Human Services [HHSN268201100046C, HHSN268201100001C, HHSN268201100002C, HHSN268201100003C, HHSN268201100004C, HHSN271201100004C] FX This work was supported by the Intramural Research Program of the National Cancer Institute, NIH, U.S. Department of Health and Human Services. The NPAAS was supported by the National Cancer Institute grant R01 CA119171-04A1 (L.F. Tinker, J.W. Lampe, M.L. Neuhouser, and R.L. Prentice). The WHI program is funded by the National Heart, Lung, and Blood Institute, NIH, U.S. Department of Health and Human Services through contracts HHSN268201100046C, HHSN268201100001C, HHSN268201100002C, HHSN268201100003C, HHSN268201100004C, and HHSN271201100004C. NR 35 TC 8 Z9 8 U1 2 U2 8 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1055-9965 EI 1538-7755 J9 CANCER EPIDEM BIOMAR JI Cancer Epidemiol. Biomarkers Prev. PD DEC PY 2014 VL 23 IS 12 BP 2874 EP 2883 DI 10.1158/1055-9965.EPI-14-0594 PG 10 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA AW0FU UT WOS:000345967300029 PM 25234237 ER PT J AU Okayama, H Schetter, AJ Ishigame, T Robles, AI Kohno, T Yokota, J Takenoshita, S Harris, CC AF Okayama, Hirokazu Schetter, Aaron J. Ishigame, Teruhide Robles, Ana I. Kohno, Takashi Yokota, Jun Takenoshita, Seiichi Harris, Curtis C. TI The Expression of Four Genes as a Prognostic Classifier for Stage I Lung Adenocarcinoma in 12 Independent Cohorts SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Article ID SQUAMOUS-CELL CARCINOMA; ADJUVANT CHEMOTHERAPY; SURVIVAL PREDICTION; CANCER PATIENTS; BREAST-CANCER; SIGNATURES; VALIDATION; METAANALYSES; ASSAY AB Background: We previously developed a prognostic classifier using the expression levels of BRCA1, HIF1A, DLC1, and XPO1 that identified stage I lung adenocarcinoma patients with a high risk of relapse. That study evaluated patients in five independent cohorts from various regions of the world. In an attempt to further validate the classifier, we have used a meta-analysis-based approach to study 12 cohorts consisting of 1,069 tumor-node-metastasis stage I lung adenocarcinoma patients from every suitable, publically available dataset. Methods: Cohorts were obtained through a systematic search of public gene expression datasets. These data were used to calculate the risk score using the previously published 4-gene risk model. A fixed effect metaanalysis model was used to generate a pooled estimate for all cohorts. Results: The classifier was associated with prognosis in 10 of the 12 cohorts (P < 0.05). This association was highly consistent regardless of the ethnic diversity or microarray platform. The pooled estimate demonstrated that patients classified as high risk had worse overall survival for all stage I [HR, 2.66; 95% confidence interval (CI), 1.93-3.67; P < 0.0001] patients and in stratified analyses of stage IA (HR, 2.69; 95% CI, 1.66-4.35; P < 0.0001) and stage IB (HR, 2.69; 95% CI, 1.74-4.16; P < 0.0001) patients. Conclusions: The 4-gene classifier provides independent prognostic stratification of stage IA and stage IB patients beyond conventional clinical factors. Impact: Our results suggest that the 4-gene classifier may assist clinicians in decisions about the postoperative management of early-stage lung adenocarcinoma patients. (C) 2014 AACR. C1 [Okayama, Hirokazu; Schetter, Aaron J.; Ishigame, Teruhide; Robles, Ana I.; Harris, Curtis C.] NCI, Ctr Canc Res, Human Carcinogenesis Lab, NIH, Bethesda, MD 20892 USA. [Kohno, Takashi] Natl Canc Ctr, Res Inst, Div Genome Biol, Tokyo 104, Japan. [Yokota, Jun] Inst Predict & Personalized Med Canc, Genom & Epigenom Canc Predict Program, Barcelona, Spain. [Takenoshita, Seiichi] Fukushima Med Univ, Sch Med, Dept Organ Regulatory Surg, Fukushima, Japan. RP Harris, CC (reprint author), NCI, Human Carcinogenesis Lab, NIH, 37 Convent Dr MSC4258,Bldg 37,Room 3068A, Bethesda, MD 20892 USA. EM Curtis_Harris@nih.gov FU Intramural Research Program of the National Cancer Institute, NIH; Department of Defense Congressionally Directed Medical Research Program [PR093793] FX This work was supported by the Intramural Research Program of the National Cancer Institute, NIH and Department of Defense Congressionally Directed Medical Research Program Grant PR093793. NR 44 TC 12 Z9 12 U1 0 U2 4 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1055-9965 EI 1538-7755 J9 CANCER EPIDEM BIOMAR JI Cancer Epidemiol. Biomarkers Prev. PD DEC PY 2014 VL 23 IS 12 BP 2884 EP 2894 DI 10.1158/1055-9965.EPI-14-0182 PG 11 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA AW0FU UT WOS:000345967300030 PM 25242053 ER PT J AU Arnold, KB Hermos, JA Anderson, KB Minasian, L Tangen, CM Probstfield, JF Cook, ED AF Arnold, Kathryn B. Hermos, John A. Anderson, Karen B. Minasian, Lori Tangen, Catherine M. Probstfield, Jeffrey F. Cook, Elise D. TI Retention of Black and White Participants in the Selenium and Vitamin E Cancer Prevention Trial (SWOG-Coordinated Intergroup Study S0000) SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Article ID AFRICAN-AMERICAN MEN; FOLLOW-UP; CLINICAL-TRIALS; PROSTATE-CANCER; MINORITY RECRUITMENT; SCREENING TRIAL; COLORECTAL-CANCER; RISK; HEALTH; SELECT AB Background: Disproportionally low retention of minority populations can adversely affect the generalizability of clinical research trials. We determine the overall retention rates for White and Black participants from the Selenium and Vitamin E Cancer Prevention Trial (SELECT) and explore participant and site characteristics associated with retention failure (study disengagement) for these groups. Methods: A secondary analysis of 28,118 White (age >= 55), and 4,322 Black (age >= 50) SELECT participants used multivariate Cox regression to estimate overall retention rates and to calculate HRs and 95% confidence intervals (CI). Results: Blacks had higher age-adjusted risk of disengagement than Whites (HR, 1.92; 95% CI, 1.77-2.08). Among Black participants, those ages 50 to 54 were at three times the risk of disengagement than those >= 65 years of age (HR, 3.61; 95% CI, 2.41-5.41). Blacks age >= 65 had 1.6 times the risk of disengagement than Whites age >= 65 (HR, 1.60; 95% CI, 1.38-1.87). By 6 years after randomization, 84% of Whites and 69% of Blacks remained engaged in the study. Current smoking status was an independent risk factor for study disengagement for both White and Black participants. For both groups, sites whose staffs missed SELECT training sessions or who received SELECT Retention and Adherence grants were associated with increased and decreased disengagement risks, respectively. Conclusions: SELECT retention was disproportionately lower for Blacks than for Whites. Impact: The observed difference in retention rates for Blacks and Whites and factors identified by race for study disengagement in SELECT may inform retention efforts for future long-term, cancer prevention trials. (C) 2014 AACR. C1 [Arnold, Kathryn B.; Tangen, Catherine M.] Fred Hutchinson Canc Res Ctr, SWOG Stat Ctr, Seattle, WA 98109 USA. [Hermos, John A.] VA Boston Healthcare Syst, VA Cooperat Studies Program, Coordinating Ctr, Boston, MA USA. [Anderson, Karen B.] SWOG Data Management Canc Res & Biostat, Seattle, WA USA. [Minasian, Lori] NCI, Div Canc Prevent, Rockville, MD USA. [Probstfield, Jeffrey F.] Univ Washington, Dept Med, Clin Trials Serv Unit, Seattle, WA USA. [Cook, Elise D.] Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA. RP Arnold, KB (reprint author), Fred Hutchinson Canc Res Ctr, SWOG Stat Ctr, 1100 Fairview Ave North,M3-C102,POB 19024, Seattle, WA 98109 USA. EM karnold@fhcrc.org FU Public Health Service Cooperative Agreement, National Cancer Institute, NIH, Department of Health and Human Services [CA37429]; National Center for Complementary and Alternative Medicine (NIH) FX This research was supported in part by Public Health Service Cooperative Agreement grant CA37429 (to K.B. Arnold, K.B. Anderson, C.M. Tangen; and PI, C. Blanke) awarded by the National Cancer Institute, NIH, Department of Health and Human Services, and in part by the National Center for Complementary and Alternative Medicine (NIH). Study agents and packaging were provided by Perrigo Company (Allegan, MI), Sabinsa Corporation (Piscataway, NJ), Tishcon Corporation (Westbury, NY), and DSM Nutritional Products Inc. NR 46 TC 2 Z9 2 U1 0 U2 2 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1055-9965 EI 1538-7755 J9 CANCER EPIDEM BIOMAR JI Cancer Epidemiol. Biomarkers Prev. PD DEC PY 2014 VL 23 IS 12 BP 2895 EP 2905 DI 10.1158/1055-9965.EPI-14-0724 PG 11 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA AW0FU UT WOS:000345967300031 PM 25242051 ER PT J AU Han, PKJ Williams, AE Haskins, A Gutheil, C Lucas, FL Klein, WMP Mazor, KM AF Han, Paul K. J. Williams, Andrew E. Haskins, Amy Gutheil, Caitlin Lucas, F. Lee Klein, William M. P. Mazor, Kathleen M. TI Individual Differences in Aversion to Ambiguity Regarding Medical Tests and Treatments: Association with Cancer Screening Cognitions SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Article ID PREFERENCES; UNCERTAINTY; RISK; LITERACY; CARE AB Background: Aversion to "ambiguity"-uncertainty about the reliability, credibility, or adequacy of information-about medical tests and treatments is an important psychological response that varies among individuals, but little is known about its nature and extent. The purpose of this study was to examine how individual-level ambiguity aversion relates to important health cognitions related to different cancer screening tests. Methods: A survey of 1,074 adults, ages 40 to 70 years, was conducted in four integrated U.S. healthcare systems. The Ambiguity Aversion in Medicine (AA-Med) scale, a measure of individual differences in aversion to ambiguity (AA) about medical tests and treatments, was administered along with measures of several cancer screening-related cognitions: perceived benefits and harms of colonoscopy, mammography, and PSA screening, and ambivalence and future intentions regarding these tests. Multivariable analyses were conducted to assess the associations between AA-Med scores and cancer screening cognitions. Results: Individual-level AA as assessed by the AA-Med scale was significantly associated (P < 0.05) with lower perceived benefits, greater perceived harms, and greater ambivalence about all three screening tests, and lower intentions for colonoscopy but not mammography or PSA screening. Conclusion: Individual-level AA is broadly and simultaneously associated with various pessimistic cognitive appraisals of multiple cancer screening tests. The breadth of these associations suggests that the influence of individual-level AA is insensitive to the degree and nonspecific with respect to the causes of ambiguity. Impact: Individual-level AA constitutes a measurable, wide-ranging cognitive bias against medical intervention, and more research is needed to elucidate its mechanisms and effects. (C) 2014 AACR. C1 [Han, Paul K. J.; Williams, Andrew E.; Haskins, Amy; Gutheil, Caitlin; Lucas, F. Lee] Maine Med Ctr, Ctr Outcomes Res Evaluat, Portland, ME 04101 USA. [Klein, William M. P.] NCI, Div Canc Control & Populat Sci, Bethesda, MD 20892 USA. [Mazor, Kathleen M.] Univ Massachusetts, Sch Med, Meyers Primary Care Inst, Worcester, MA USA. RP Han, PKJ (reprint author), Maine Med Ctr, Ctr Outcomes Res Evaluat, 509 Forest Ave, Portland, ME 04101 USA. EM hanp@mmc.org OI Han, Paul/0000-0003-0165-1940 FU National Cancer Institute [U19 CA079689] FX This work was supported by the National Cancer Institute (grant U19 CA079689; to K.M. Mazor, A.E. Williams, and P.K.J. Han). NR 18 TC 3 Z9 3 U1 0 U2 2 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1055-9965 EI 1538-7755 J9 CANCER EPIDEM BIOMAR JI Cancer Epidemiol. Biomarkers Prev. PD DEC PY 2014 VL 23 IS 12 BP 2916 EP 2923 DI 10.1158/1055-9965.EPI-14-0872 PG 8 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA AW0FU UT WOS:000345967300033 PM 25258015 ER PT J AU Du, MM Zhang, XH Hoffmeister, M Schoen, RE Baron, JA Berndt, SI Brenner, H Carlson, CS Casey, G Chan, AT Curtis, KR Duggan, D Gauderman, WJ Giovannucci, EL Gong, J Harrison, TA Hayes, RB Henderson, BE Hopper, JL Hsu, L Hudson, TJ Hutter, CM Jenkins, MA Jiao, S Kocarnik, JM Kolonel, LN Le Marchand, L Lin, Y Newcomb, PA Rudolph, A Seminara, D Thornquist, MD Ulrich, CM White, E Wu, K Zanke, BW Campbell, PT Slattery, ML Peters, U Chang-Claude, J Potter, JD AF Du, Mengmeng Zhang, Xuehong Hoffmeister, Michael Schoen, Robert E. Baron, John A. Berndt, Sonja I. Brenner, Hermann Carlson, Christopher S. Casey, Graham Chan, Andrew T. Curtis, Keith R. Duggan, David Gauderman, W. James Giovannucci, Edward L. Gong, Jian Harrison, Tabitha A. Hayes, Richard B. Henderson, Brian E. Hopper, John L. Hsu, Li Hudson, Thomas J. Hutter, Carolyn M. Jenkins, Mark A. Jiao, Shuo Kocarnik, Jonathan M. Kolonel, Laurence N. Le Marchand, Loic Lin, Yi Newcomb, Polly A. Rudolph, Anja Seminara, Daniela Thornquist, Mark D. Ulrich, Cornelia M. White, Emily Wu, Kana Zanke, Brent W. Campbell, Peter T. Slattery, Martha L. Peters, Ulrike Chang-Claude, Jenny Potter, John D. CA Colon Canc Family Registry Geneti TI No Evidence of Gene-Calcium Interactions from Genome-Wide Analysis of Colorectal Cancer Risk SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Article ID ENVIRONMENT INTERACTIONS; SUSCEPTIBILITY LOCI; METAANALYSIS AB Background: Calcium intake may reduce risk of colorectal cancer, but the mechanisms remain unclear. Studies of interaction between calcium intake and SNPs in calcium-related pathways have yielded inconsistent results. Methods: To identify gene-calcium interactions, we tested interactions between approximately 2.7 million SNPs across the genome with self-reported calcium intake (from dietary or supplemental sources) in 9,006 colorectal cancer cases and 9,503 controls of European ancestry. To test for multiplicative interactions, we used multivariable logistic regression and defined statistical significance using the conventional genome-wide alpha = 5E-08. Results: After accounting for multiple comparisons, there were no statistically significant SNP interactions with total, dietary, or supplemental calcium intake. Conclusions: We found no evidence of SNP interactions with calcium intake for colorectal cancer risk in a large population of 18,509 individuals. Impact: These results suggest that in genome-wide analysis common genetic variants do not strongly modify the association between calcium intake and colorectal cancer in European populations. (C) 2014 AACR. C1 [Du, Mengmeng; Carlson, Christopher S.; Curtis, Keith R.; Gong, Jian; Harrison, Tabitha A.; Hsu, Li; Hutter, Carolyn M.; Jiao, Shuo; Kocarnik, Jonathan M.; Lin, Yi; Newcomb, Polly A.; Thornquist, Mark D.; Ulrich, Cornelia M.; White, Emily; Peters, Ulrike; Potter, John D.] Fred Hutchinson Canc Res Ctr, Publ Hlth Sci Div, Seattle, WA 98109 USA. [Du, Mengmeng; Kocarnik, Jonathan M.; Newcomb, Polly A.; Ulrich, Cornelia M.; White, Emily; Peters, Ulrike; Potter, John D.] Univ Washington, Sch Publ Hlth, Seattle, WA 98195 USA. [Du, Mengmeng; Zhang, Xuehong; Chan, Andrew T.; Giovannucci, Edward L.] Brigham & Womens Hosp, Channing Div Network Med, Boston, MA 02115 USA. [Du, Mengmeng; Zhang, Xuehong; Chan, Andrew T.; Giovannucci, Edward L.] Harvard Univ, Sch Med, Boston, MA 02115 USA. [Hoffmeister, Michael; Brenner, Hermann] German Canc Res Ctr, Div Clin Epidemiol & Aging Res, Heidelberg, Germany. [Schoen, Robert E.] Univ Pittsburgh, Med Ctr, Dept Med & Epidemiol, Pittsburgh, PA USA. [Baron, John A.] Univ N Carolina, Sch Med, Dept Med, Chapel Hill, NC USA. [Berndt, Sonja I.] NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. [Brenner, Hermann] German Canc Consortium DKTK, Heidelberg, Germany. [Casey, Graham] Univ So Calif, Dept Prevent Med, Los Angeles, CA 90089 USA. [Chan, Andrew T.] Massachusetts Gen Hosp, Div Gastroenterol, Boston, MA 02114 USA. [Chan, Andrew T.] Harvard Univ, Sch Med, Boston, MA 02115 USA. [Duggan, David] Genet Basis Human Dis Translat Genom Res Inst TGe, Phoenix, AZ USA. [Gauderman, W. James] Univ So Calif, Keck Sch Med, Los Angeles, CA 90033 USA. [Giovannucci, Edward L.; Wu, Kana] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. [Giovannucci, Edward L.] Harvard Univ, Sch Publ Hlth, Dept Nutr, Boston, MA 02115 USA. [Hayes, Richard B.; Jenkins, Mark A.] NYU, Sch Med, Dept Populat Hlth, Div Epidemiol, New York, NY USA. [Hopper, John L.; Jenkins, Mark A.] Univ Melbourne, Melbourne Sch Populat & Global Hlth, Melbourne, Vic, Australia. [Hudson, Thomas J.] Ontario Inst Canc Res, Toronto, ON, Canada. [Hudson, Thomas J.] Univ Toronto, Dept Med Biophys, Toronto, ON, Canada. [Hudson, Thomas J.] Univ Toronto, Dept Mol Genet, Toronto, ON, Canada. [Hutter, Carolyn M.; Seminara, Daniela; Chang-Claude, Jenny] NCI, Div Canc Control & Populat Sci, Bethesda, MD 20892 USA. [Kolonel, Laurence N.; Le Marchand, Loic] Univ Hawaii, Ctr Canc, Program Epidemiol, Honolulu, HI 96822 USA. [Rudolph, Anja] German Canc Res Ctr, Div Canc Epidemiol, Unit Genet Epidemiol, Heidelberg, Germany. [Ulrich, Cornelia M.] Natl Ctr Tumor Dis NCT, Heidelberg, Germany. [Zanke, Brent W.] Univ Ottawa, Fac Med, Div Hematol, Ottawa, ON, Canada. [Campbell, Peter T.] Amer Canc Soc, Epidemiol Res Program, Atlanta, GA 30329 USA. [Slattery, Martha L.] Univ Utah, Hlth Sci Ctr, Dept Internal Med, Salt Lake City, UT USA. [Potter, John D.] Massey Univ, Ctr Publ Hlth Res, Wellington, New Zealand. RP Du, MM (reprint author), Fred Hutchinson Canc Res Ctr, Canc Prevent Program, 1100 Fairview Ave North,M4-B402, Seattle, WA 98109 USA. EM mdu@fhcrc.org RI Hoffmeister, Michael/B-5745-2012; Brenner, Hermann/B-4627-2017; Jenkins, Mark/P-7803-2015; OI Hoffmeister, Michael/0000-0002-8307-3197; Brenner, Hermann/0000-0002-6129-1572; Potter, John/0000-0001-5439-1500; Jenkins, Mark/0000-0002-8964-6160; Hayes, Richard/0000-0002-0918-661X FU National Cancer Institute, NIH, U.S. Department of Health and Human Services [U01 CA137088, R01 CA059045]; NIH [R01 CA60987, R01 CA48998, P01 CA 055075, UM1 CA167552, R01 137178, P50 CA127003, R01 CA137178, P01 CA 087969, P50 CA 127003, R01 CA42182, R37 CA54281, P01 CA033619, R01 CA63464, U01 CA074783, U01 HG004446, R01 CA076366]; NIH (RFA) [CA-95011]; National Cancer Institute, NIH [U01 CA122839, R25 CA94880]; NIH: Australasian Colorectal Cancer Family Registry [U01 CA097735]; Ontario Registry for Studies of Familial Colorectal Cancer [U01 CA074783]; Seattle Colorectal Cancer Family Registry [U01 CA074794]; German Research Council (Deutsche Forschungsgemeinschaft) [BR 17046-1, BR 17046-3, BR 17046-4, CH1171-1]; German Federal Ministry of Education and Research [01KH0404, 01ER0814]; Ontario Research Fund; Canadian Institutes of Health Research; Ontario Institute for Cancer Research, through Ontario Ministry of Research and Innovation; Intramural Research Program of the Division of Cancer Epidemiology and Genetics; Division of Cancer Prevention, National Cancer Institute, NIH, DHHS; National Institutes of Health (NIH) Genes, Environment, and Health Initiative (GEI) [Z01 CP 010200]; NIH GEI [U01 HG 004438]; NIH from the National Cancer Institute [K05 CA154337]; NIH from the Office of Dietary Supplements; ACS; GECCO [R01 CA059045]; National Institutes of Environmental Health Sciences [ES020801]; National Heart, Lung, and Blood Institute, NIH, U.S. Department of Health and Human Services [HHSN268201100046C, HHSN268201100001C, HHSN268201100002C, HHSN268201100003C, HHSN268201100004C, HHSN271201100004C]; [U19 CA148107] FX C.S. Carlson, K.R. Curtis, M. Du, J. Gong, T. A. Harrison, L. Hsu, C.M. Hutter, J.M. Kocarnik, S. Jiao, Y. Lin, U. Peters, M.D. Thornquist, and C.M. Ulrich are affiliated with GECCO, which is supported by the following grants from the National Cancer Institute, NIH, U.S. Department of Health and Human Services: U01 CA137088 and R01 CA059045.; L. Le Marchand is affiliated with COLO2& 3, which is supported by the NIH (R01 CA60987).; J.A. Baron, G. Casey, J.L. Hopper, M.A. Jenkins, and P.A. Newcomb are affiliated with CCFR, which is supported by the NIH (RFA # CA-95011) and through cooperative agreements with members of the Colon Cancer Family Registry and P.I.s. This genome-wide scan was supported by the National Cancer Institute, NIH by U01 CA122839. The following Colon CFR centers contributed data to this article and were supported by NIH: Australasian Colorectal Cancer Family Registry (U01 CA097735), Ontario Registry for Studies of Familial Colorectal Cancer (U01 CA074783), and Seattle Colorectal Cancer Family Registry (U01 CA074794).; H. Brenner, J. Chang-Claude, M. Hoffmeister, and A. Rudolph are affiliated with DACHS, which was supported by grants from the German Research Council (Deutsche Forschungsgemeinschaft, BR 17046-1, BR 17046-3, BR 17046-4 and CH1171-1), and the German Federal Ministry of Education and Research (01KH0404 and 01ER0814).; J.D. Potter and M.L. Slattery are affiliated with DALS, which was supported by the NIH (R01 CA48998 to M.L. Slattery). A.T. Chan, E.L. Giovannucci, K. Wu, and X. Zhang are affiliated with HPFS, NHS, and PHS. HPFS was supported by the NIH (P01 CA 055075, UM1 CA167552, R01 137178, and P50 CA127003), NHS by the NIH (R01 CA137178, P01 CA 087969, and P50 CA 127003), and PHS by the NIH (R01 CA42182).; B.E. Henderson, L.N. Kolonel, and L. Le Marchand are affiliated with MEC, which is supported by the following grants from the NIH: R37 CA54281, P01 CA033619, and R01 CA63464.; T.J. Hudson and B.W. Zanke are affiliated with OFCCR, which is supported by the NIH, through funding allocated to the Ontario Registry for Studies of Familial Colorectal Cancer (U01 CA074783); see CCFR section above. Additional funding toward genetic analyses of OFCCR includes the Ontario Research Fund, the Canadian Institutes of Health Research, and the Ontario Institute for Cancer Research, through generous support from the Ontario Ministry of Research and Innovation.; S.I. Berndt, R.B. Hayes, and R.E. Schoen are affiliated with PLCO, which was supported by the Intramural Research Program of the Division of Cancer Epidemiology and Genetics and supported by contracts from the Division of Cancer Prevention, National Cancer Institute, NIH, DHHS. In addition, a subset of control samples were genotyped as part of the Cancer Genetic Markers of Susceptibility (CGEMS) Prostate Cancer GWAS (Yeager, M and colleagues Genome-wide association study of prostate cancer identifies a second risk locus at 8q24. Nat Genet. 2007 May; 39(5): 645-9), Colon CGEMS pancreatic cancer scan (PanScan; Amundadottir, L and colleagues Genome-wide association study identifies variants in the ABO locus associated with susceptibility to pancreatic cancer. Nat Genet. 2009 Sep;41(9):986-90, and Petersen, GM and colleagues A genome-wide association study identifies pancreatic cancer susceptibility loci on chromosomes 13q22.1, 1q32.1 and 5p15.33. Nat Genet. 2010 Mar;42(3):224-8), and the Lung Cancer and Smoking study (Landi MT, and colleagues A genome-wide association study of lung cancer identifies a region of chromosome 5p15 associated with risk for adenocarcinoma. Am J Hum Genet. 2009 Nov;85(5):679-91). The prostate and PanScan study datasets were accessed with appropriate approval through the dbGaP online resource (http://cgems.cancer.gov/data/) accession numbers phs000207.v1.p1 and phs000206.v3.p2, respectively, and the lung datasets were accessed from the dbGaP website (http://www.ncbi.nlm.nih.gov/gap) through accession number phs000093.v2.p2. Funding for the Lung Cancer and Smoking study was provided by National Institutes of Health (NIH), Genes, Environment, and Health Initiative (GEI) Z01 CP 010200, NIH U01 HG004446, and NIH GEI U01 HG 004438. For the lung study, the GENEVA Coordinating Center provided assistance with genotype cleaning and general study coordination, and the Johns Hopkins University Center for Inherited Disease Research conducted genotyping.; P.A. Newcomb is affiliated with PMH, which is supported by the NIH (R01 CA076366 to P.A. Newcomb). E. White is affiliated with VITAL, which is supported in part by the NIH (K05 CA154337) from the National Cancer Institute and Office of Dietary Supplements.; P.T. Campbell is at the American Cancer Society (ACS) and funded through ACS.; M. Du is supported by the National Cancer Institute, NIH (R25 CA94880).; D. Duggan is affiliated with TGEN and funded through a subaward with GECCO (R01 CA059045).; W.J. Gauderman is affiliated with Colorectal Transdisciplinary Study (CORECT), which is funded through U19 CA148107, and by the National Institutes of Environmental Health Sciences (ES020801).; D. Seminara is a Senior Scientist and Consortia Coordinator at the Epidemiology and Genetics Research Program, Division of Cancer Control and Population Sciences, National Cancer Institute, NIH.; The WHI program is funded by the National Heart, Lung, and Blood Institute, NIH, U.S. Department of Health and Human Services through contracts HHSN268201100046C, HHSN268201100001C, HHSN268201100002C, HHSN268201100003C, HHSN268201100004C, and HHSN271201100004C. NR 8 TC 1 Z9 1 U1 0 U2 3 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1055-9965 EI 1538-7755 J9 CANCER EPIDEM BIOMAR JI Cancer Epidemiol. Biomarkers Prev. PD DEC PY 2014 VL 23 IS 12 BP 2971 EP 2976 DI 10.1158/1055-9965.EPI-14-0893 PG 6 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA AW0FU UT WOS:000345967300040 PM 25192705 ER PT J AU Kim, C Bassig, BA Seow, WJ Hu, W Purdue, MP Shu, XO Huang, WY Liu, CS Cheng, WL Lin, TT Xiang, YB Ji, BT Gao, YT Chow, WH Mannisto, S Weinstein, SJ Albanes, D Zheng, W Hosgood, HD Lim, U Rothman, N Lan, Q AF Kim, Christopher Bassig, Bryan A. Seow, Wei Jie Hu, Wei Purdue, Mark P. Shu, Xiao-Ou Huang, Wen-Yi Liu, Chin-San Cheng, Wen-Ling Lin, Ta-Tsung Xiang, Yong-Bing Ji, Bu-Tian Gao, Yu-Tang Chow, Wong-Ho Maennistoe, Satu Weinstein, Stephanie J. Albanes, Demetrius Zheng, Wei Hosgood, H. Dean Lim, Unhee Rothman, Nathaniel Lan, Qing TI Pooled Analysis of Mitochondrial DNA Copy Number and Lung Cancer Risk in Three Prospective Studies SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Article ID OXIDATIVE STRESS AB Background: We previously reported that higher levels of mitochondrial DNA copy number (mtDNA CN) were associated with lung cancer risk among male heavy smokers (i.e., >= 20 cigarettes per day) in the Alpha-Tocopherol Beta-Carotene (ATBC) study. Here, we present two additional prospective investigations nested in the Prostate, Lung, Colorectal, and Ovarian (PLCO) cancer screening trial and the Shanghai Women's Health Study (SWHS), and pooled with previously published data from ATBC. Materials: All DNA were extracted from peripheral whole blood samples using the phenol-chloroform method, and mtDNA CN was assayed by fluorescence-based qPCR. Multivariate unconditional logistic regression models were used to estimate ORs and 95% confidence intervals for the association of mtDNA CN and lung cancer risk. Results: Overall, mtDNA CN was not associated with lung cancer risk in the PLCO, SWHS, or pooled populations (all P trends > 0.42, P heterogeneity = 0.0001), and mtDNA CN was inversely associated with lung cancer risk among male smokers in PLCO, the opposite direction observed in ATBC. In addition, the mtDNA CN association observed among male heavy smokers in ATBC was the opposite direction in PLCO. Conclusions: mtDNA CN was not consistently associated with lung cancer risk across three prospective study populations from Europe, Asia, and the United States. Impact: This pooled study suggests no consistent association between prediagnostic mtDNA CN levels and lung cancer risk across several populations. (C) 2014 AACR. C1 [Kim, Christopher; Bassig, Bryan A.; Seow, Wei Jie; Hu, Wei; Purdue, Mark P.; Huang, Wen-Yi; Ji, Bu-Tian; Weinstein, Stephanie J.; Albanes, Demetrius; Rothman, Nathaniel; Lan, Qing] NCI, Div Canc Epidemiol & Genet, NIH, Bethesda, MD 20892 USA. [Shu, Xiao-Ou; Zheng, Wei] Vanderbilt Univ, Med Ctr, Nashville, TN USA. [Liu, Chin-San; Cheng, Wen-Ling; Lin, Ta-Tsung] Changhua Christian Hosp, Neurol & Vasc & Genom Ctr, Changhua, Taiwan. [Xiang, Yong-Bing] Shanghai Jiao Tong Univ, Sch Med, Renji Hosp, Shanghai Canc Inst, Shanghai 200030, Peoples R China. [Gao, Yu-Tang] Shanghai Canc Inst, Shanghai, Peoples R China. [Chow, Wong-Ho] Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA. [Maennistoe, Satu] Natl Inst Hlth & Welf, Dept Chron Dis Prevent, Helsinki, Finland. [Hosgood, H. Dean] Yeshiva Univ Albert Einstein Coll Med, Bronx, NY 10461 USA. [Lim, Unhee] Univ Hawaii, Ctr Canc, Program Epidemiol, Honolulu, HI 96822 USA. RP Kim, C (reprint author), NCI, NIH, 9609 Med Ctr Dr,MSSC 9771, Bethesda, MD 20892 USA. EM christopher.kim@nih.gov RI Albanes, Demetrius/B-9749-2015; Purdue, Mark/C-9228-2016; OI Purdue, Mark/0000-0003-1177-3108; Mannisto, Satu/0000-0002-8668-3046 FU NIH intramural research program FX This study was supported by NIH intramural research program. NR 8 TC 3 Z9 3 U1 0 U2 1 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1055-9965 EI 1538-7755 J9 CANCER EPIDEM BIOMAR JI Cancer Epidemiol. Biomarkers Prev. PD DEC PY 2014 VL 23 IS 12 BP 2977 EP 2980 DI 10.1158/1055-9965.EPI-14-1070 PG 4 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA AW0FU UT WOS:000345967300041 PM 25293879 ER PT J AU Tucker, JA Jochems, C Boyerinas, B Fallon, J Greiner, JW Palena, C Rodell, TC Schlom, J Tsang, KY AF Tucker, Jo A. Jochems, Caroline Boyerinas, Benjamin Fallon, Jonathan Greiner, John W. Palena, Claudia Rodell, Timothy C. Schlom, Jeffrey Tsang, Kwong-Yok TI Identification and characterization of a cytotoxic T-lymphocyte agonist epitope of brachyury, a transcription factor involved in epithelial to mesenchymal transition and metastasis SO CANCER IMMUNOLOGY IMMUNOTHERAPY LA English DT Article DE Agonist epitope; Brachyury; Cytotoxic T lymphocytes (CTL); Epithelial to mesenchymal transition (EMT); Immunotherapy; Saccharomyces cerevisiae vector ID PROSTATE-SPECIFIC ANTIGEN; CARCINOEMBRYONIC ANTIGEN; TUMOR-CELLS; VACCINE; CANCER; PROGRESSION; EXPRESSION; RESISTANCE; REGULATOR; TARGET AB The transcription factor brachyury is a major driver of epithelial to mesenchymal transition in human carcinoma cells. It is overexpressed in several human tumor types versus normal adult tissues, except for testes and thyroid. Overexpression is associated with drug resistance and poor prognosis. Previous studies identified a brachyury HLA-A2 cytotoxic T-lymphocyte epitope. The studies reported here describe an enhancer epitope of brachyury. Compared to the native epitope, the agonist epitope: (a) has enhanced binding to MHC class I, (b) increased the IFN-gamma production from brachyury-specific T cells, (c) generated brachyury-specific T cells with greater levels of perforin and increased proliferation, (d) generated T cells more proficient at lysing human carcinoma cells endogenously expressing the native epitope, and (e) achieved greater brachyury-specific T-cell responses in vivo in HLA-A2 transgenic mice. These studies also report the generation of a heat-killed recombinant Saccharomyces cerevisiae (yeast) vector expressing the full-length brachyury gene encoding the agonist epitope. Compared to yeast-brachyury (native) devoid of the agonist epitope, the yeast-brachyury (agonist) enhanced the activation of brachyury-specific T cells, which efficiently lysed human carcinoma cells. In addition to providing the rationale for the recombinant yeast-brachyury (agonist) as a potential vaccine in cancer therapy, these studies also provide the rationale for the use of the agonist in (a) dendritic cell (DC) vaccines, (b) adjuvant or liposomal vaccines, (c) recombinant viral and/or bacterial vaccines, (d) protein/polypeptide vaccines, (e) activation of T cells ex vivo in adoptive therapy protocols, and (f) generation of genetically engineered targeted T cells. C1 [Tucker, Jo A.; Jochems, Caroline; Boyerinas, Benjamin; Fallon, Jonathan; Greiner, John W.; Palena, Claudia; Schlom, Jeffrey; Tsang, Kwong-Yok] NCI, Lab Tumor Immunol & Biol, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. [Rodell, Timothy C.] GlobeImmune Inc, Louisville, CO 80027 USA. RP Schlom, J (reprint author), NCI, Lab Tumor Immunol & Biol, Ctr Canc Res, NIH, 10 Ctr Dr,Room 8B09,MSC 1750, Bethesda, MD 20892 USA. EM js141c@nih.gov FU Intramural Research Program of the Center for Cancer Research, National Cancer Institute, National Institutes of Health; National Cancer Institute; GlobeImmune, Inc. FX Grant support was provided by the Intramural Research Program of the Center for Cancer Research, National Cancer Institute, National Institutes of Health, and a Cooperative Research and Development Agreement between the National Cancer Institute and GlobeImmune, Inc. The authors thank Diane J. Poole, Garland Davis and Curtis Randolph for technical assistance and Debra Weingarten for editorial assistance in the preparation of this manuscript. NR 39 TC 15 Z9 15 U1 1 U2 6 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0340-7004 EI 1432-0851 J9 CANCER IMMUNOL IMMUN JI Cancer Immunol. Immunother. PD DEC PY 2014 VL 63 IS 12 BP 1307 EP 1317 DI 10.1007/s00262-014-1603-2 PG 11 WC Oncology; Immunology SC Oncology; Immunology GA AW0EK UT WOS:000345963000007 PM 25186612 ER PT J AU Brown, AW Hall, KD Thomas, D Dhurandhar, NV Heymsfield, SB Allison, DB AF Brown, Andrew W. Hall, Kevin D. Thomas, Diana Dhurandhar, Nikhil V. Heymsfield, Steven B. Allison, David B. TI Order of Magnitude Misestimation of Weight Effects of Children's Meal Policy Proposals SO CHILDHOOD OBESITY LA English DT Letter ID POUND; RULE C1 [Brown, Andrew W.; Allison, David B.] Univ Alabama Birmingham, Off Energet, Nutr & Obes Res Ctr, Birmingham, AL 35294 USA. [Hall, Kevin D.] NIDDKD, Lab Biol Modeling, NIH, Bethesda, MD USA. [Thomas, Diana] Montclair State Univ, Ctr Quantitat Obes Res, Montclair, NJ USA. [Dhurandhar, Nikhil V.; Heymsfield, Steven B.] Louisiana State Univ Syst, Pennington Biomed Res Ctr, Baton Rouge, LA USA. [Allison, David B.] Univ Alabama Birmingham, Dept Nutr Sci, Birmingham, AL 35294 USA. RP Brown, AW (reprint author), Univ Alabama Birmingham, Off Energet, Nutr & Obes Res Ctr, 435 Lister Hall Lib, Birmingham, AL 35294 USA. EM awbrown@uab.edu OI Allison, David/0000-0003-3566-9399; Brown, Andrew/0000-0002-1758-8205 FU NIDDK NIH HHS [P30 DK056336] NR 16 TC 4 Z9 4 U1 0 U2 1 PU MARY ANN LIEBERT, INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 2153-2168 EI 2153-2176 J9 CHILD OBES JI Child Obes. PD DEC 1 PY 2014 VL 10 IS 6 BP 542 EP 544 DI 10.1089/chi.2014.0081 PG 3 WC Pediatrics SC Pediatrics GA AW1SN UT WOS:000346070300012 PM 25496036 ER PT J AU Luo, FR Ding, J Chen, HX Liu, H Fung, MC Koehler, M Armand, JP Jiang, L Xu, X Zhang, G Xu, L Qian, P Yan, L AF Luo, Feng Roger Ding, Jian Chen, Helen X. Liu, Hao Fung, Man-Cheong Koehler, Maria Armand, Jean Pierre Jiang, Lei Xu, Xiao Zhang, Ge Xu, Li Qian, Pascal Yan, Li TI Breakthrough cancer medicine and its impact on novel drug development in China: report of the US Chinese Anti-Cancer Association (USCACA) and Chinese Society of Clinical Oncology (CSCO) Joint Session at the 17th CSCO Annual Meeting SO CHINESE JOURNAL OF CANCER LA English DT Review DE Breakthrough; clinical trial; cancer medicine ID CELL LUNG-CANCER; GASTRIC-CANCER; BREAST-CANCER; INHIBITOR; PCI-32765; IBRUTINIB AB The US Chinese Anti-Cancer Association (USCACA) teamed up with Chinese Society of Clinical Oncology (CSCO) to host a joint session at the 17th CSCO Annual Meeting on September 20th, 2014 in Xiamen, China. With a focus on breakthrough cancer medicines, the session featured innovative approaches to evaluate breakthrough agents and established a platform to interactively share successful experiences from case studies of 6 novel agents from both the United States and China. The goal of the session is to inspire scientific and practical considerations for clinical trial design and strategy to expedite cancer drug development in China. A panel discussion further provided in-depth advice on advancing both early and full development of novel cancer medicines in China. C1 [Luo, Feng Roger; Chen, Helen X.; Xu, Xiao; Xu, Li; Qian, Pascal; Yan, Li] US Chinese Anticanc Assoc, Martinez, CA 94553 USA. [Luo, Feng Roger; Fung, Man-Cheong] Janssen Res & Dev LLC, Dept Oncol, Raritan, NJ 08869 USA. [Ding, Jian; Jiang, Lei] Chinese Acad Sci, Shanghai Inst Mat Med, Shanghai 201203, Peoples R China. [Chen, Helen X.] NCI, Canc Therapy Evaluat Program, Bethesda, MD 20892 USA. [Liu, Hao; Qian, Pascal] Novartis Pharmaceut China Oncol, Beijing 10004, Peoples R China. [Koehler, Maria] Pfizer Oncol, New York, NY 10017 USA. [Armand, Jean Pierre] Inst Gustave Roussy, F-94805 Villejuif, France. [Xu, Xiao] ACEA Biosci Inc, San Diego, CA 92121 USA. [Zhang, Ge; Xu, Li] Jiangsu Hengrui Med Co Ltd, Shanghai 200122, Peoples R China. [Yan, Li] Peking Univ, Beijing Canc Hosp & Inst, Sch Oncol, Beijing 100142, Peoples R China. RP Luo, FR (reprint author), US Chinese Anticanc Assoc, Martinez, CA 94553 USA. EM Rluo1@its.jnj.com; ynyinternational@yahoo.com NR 24 TC 0 Z9 0 U1 4 U2 7 PU SUN YAT SEN UNIV MED SCI WHO PI GUANGZHOU PA 651 DONGFENG RD E, GUANGZHOU, GUANGDONG 510060, PEOPLES R CHINA SN 1000-467X EI 1944-446X J9 CHIN J CANCER JI Chin. J. Cancer PD DEC PY 2014 VL 33 IS 12 BP 620 EP 624 DI 10.5732/cjc.014.10246 PG 5 WC Oncology SC Oncology GA AW4CH UT WOS:000346228500007 PM 25418191 ER PT J AU Berkowitz, JL Janik, JE Stewart, DM Jaffe, ES Stetler-Stevenson, M Shih, JH Fleisher, TA Turner, M Urquhart, NE Wharfe, GH Figg, WD Peer, CJ Goldman, CK Waldmann, TA Morris, JC AF Berkowitz, Jonathan L. Janik, John E. Stewart, Donn M. Jaffe, Elaine S. Stetler-Stevenson, Maryalice Shih, Joanna H. Fleisher, Thomas A. Turner, Maria Urquhart, Nicole E. Wharfe, Gillian H. Figg, William D. Peer, Cody J. Goldman, Carolyn K. Waldmann, Thomas A. Morris, John C. TI Safety, efficacy, and pharmacokinetics/pharmacodynamics of daclizumab (anti-CD25) in patients with adult T-cell leukemia/lymphoma SO CLINICAL IMMUNOLOGY LA English DT Article DE Adult T-cell leukemia/lymphoma; Daclizumab; Human T-cell leukemia virus 1 (HTLV-1) associated ATL; Interleukin-2 receptor alpha; Monoclonal antibody ID LEUKEMIA-LYMPHOMA VIRUS; AND/OR PARACRINE GROWTH; HUMANIZED ANTI-TAC; RENAL-TRANSPLANTATION; MULTIPLE-SCLEROSIS; CLINICAL-TRIALS; IL-2 RECEPTOR; THERAPY; INTERLEUKIN-2-RECEPTOR; BLOCKADE AB Interleukin-2 receptor a chain (CD25) is overexpressed in human T-cell leukemia virus 1 associated adult T-cell leukemia! lymphoma (ATL). Daclizumab a humanized monoclonal antibody blocks IL-2 binding by recognizing the interleukin-2 receptor a chain (CD25). We conducted a phase I/II trial of daclizumab in 34 patients with ATL. Saturation of surface CD25 on circulating ATL cells was achieved at all doses; however saturation on ATL cells in lymph nodes required 8 mg/kg. Up to 8 mg/kg of daclizumab administered every 3 weeks was well tolerated. No responses were observed in 18 patients with acute or lymphoma ATL; however, 6 partial responses were observed in 16 chronic and smoldering ATL patients. The pharmacokinetics/ pharmacodynamics of daclizumab suggest that high-dose daclizumab would be more effective than low-dose daclizumab in treatment of lymphoid malignancies and autoimmune diseases (e.g., multiple sclerosis) since high-dose daclizumab is required to saturate IL-2R alpha in extravascular sites. Published by Elsevier Inc. C1 [Berkowitz, Jonathan L.; Janik, John E.; Stewart, Donn M.; Goldman, Carolyn K.; Waldmann, Thomas A.; Morris, John C.] NCI, Lymphoid Malignancies Branch, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. [Jaffe, Elaine S.; Stetler-Stevenson, Maryalice] NCI, Pathol Lab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. [Shih, Joanna H.] NCI, Biometr Res Branch, NIH, Bethesda, MD 20892 USA. [Fleisher, Thomas A.] NIH, Dept Clin Pathol, Bethesda, MD 20892 USA. [Turner, Maria] NCI, Dermatol Branch, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. [Urquhart, Nicole E.; Wharfe, Gillian H.] Univ W Indies, Dept Haematol & Pathol, Jamaica, NY USA. [Figg, William D.; Peer, Cody J.] NCI, Med Oncol Branch, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. RP Waldmann, TA (reprint author), NIH, Ctr Canc Res, Lymphoid Malignancies Branch, 10 Ctr Dr,Bldg 10,Room 4N115, Bethesda, MD 20892 USA. EM tawald@helix.nih.gov RI Figg Sr, William/M-2411-2016 FU Intramural Research Program of the National Cancer Institute, Center for Cancer Research, National Institutes of Health FX The work was supported by the Intramural Research Program of the National Cancer Institute, Center for Cancer Research, National Institutes of Health. NR 44 TC 16 Z9 18 U1 2 U2 14 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1521-6616 EI 1521-7035 J9 CLIN IMMUNOL JI Clin. Immunol. PD DEC PY 2014 VL 155 IS 2 BP 176 EP 187 DI 10.1016/j.clim.2014.09.012 PG 12 WC Immunology SC Immunology GA AW2JQ UT WOS:000346114300003 PM 25267440 ER PT J AU Symonds, JM Hoffman, MP AF Symonds, Jennifer M. Hoffman, Matthew P. TI Luminal Signaling: It's What's on the Inside that Counts SO DEVELOPMENTAL CELL LA English DT Editorial Material ID MORPHOGENESIS; TISSUE AB During organogenesis, FGFs are diffusible communication signals that allow cells to coordinate morphogenesis and establish tissue architecture. Recently in Nature, Durdu et al. (2014) show that epithelial cell clusters secrete FGFs into a microlumen, restricting FGF localization so that participating cells coordinate differentiation and collective migration via luminal signaling. C1 [Symonds, Jennifer M.; Hoffman, Matthew P.] NIDCR, Matrix & Morphogenesis Sect, NIH, Bethesda, MD 20892 USA. RP Hoffman, MP (reprint author), NIDCR, Matrix & Morphogenesis Sect, NIH, Bethesda, MD 20892 USA. EM mhoffman@mail.nih.gov FU Intramural NIH HHS NR 7 TC 0 Z9 0 U1 0 U2 1 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 1534-5807 EI 1878-1551 J9 DEV CELL JI Dev. Cell PD DEC PY 2014 VL 31 IS 5 BP 519 EP 520 DI 10.1016/j.devcel.2014.11.019 PG 2 WC Cell Biology; Developmental Biology SC Cell Biology; Developmental Biology GA AW2JB UT WOS:000346112800002 PM 25490261 ER PT J AU Kindberg, AA Bendriem, RM Spivak, CE Chen, J Handreck, A Lupica, CR Liu, J Freed, WJ Lee, CT AF Kindberg, Abigail A. Bendriem, Raphael M. Spivak, Charles E. Chen, Jia Handreck, Annelie Lupica, Carl R. Liu, Jinny Freed, William J. Lee, Chun-Ting TI An in vitro model of human neocortical development using pluripotent stem cells: cocaine-induced cytoarchitectural alterations SO DISEASE MODELS & MECHANISMS LA English DT Article DE Neocortical development; Dorsal forebrain model; hPSCs; Cocaine; Premature neuronal differentiation ID DEVELOPING CEREBRAL-CORTEX; NEUROTROPHIC FACTOR; SIGMA-1 RECEPTOR; LAMINAR FATE; INTERNEURONS; NEURONS; PROLIFERATION; INHIBITION; MONKEY; MOUSE AB Neocortical development involves ordered specification of forebrain cortical progenitors to various neuronal subtypes, ultimately forming the layered cortical structure. Modeling of this process using human pluripotent stem cells (hPSCs) would enable mechanistic studies of human neocortical development, while providing new avenues for exploration of developmental neocortical abnormalities. Here, we show that preserving hPSCs aggregates - allowing embryoid body formation - while adding basic fibroblast growth factor (bFGF) during neuroepithelial development generates neural rosettes showing dorsal forebrain identity, including Mash1(+) dorsal telencephalic GABAergic progenitors. Structures that mirrored the organization of the cerebral cortex formed after rosettes were seeded and cultured for 3 weeks in the presence of FGF18, BDNF and NT3. Neurons migrated along radial glia scaffolding, with deep-layer CTIP2(+) cortical neurons appearing after 1 week and upper-layer SATB2(+) cortical neurons forming during the second and third weeks. At the end of differentiation, these structures contained both glutamatergic and GABAergic neurons, with glutamatergic neurons being most abundant. Thus, this differentiation protocol generated an hPSC-based model that exhibits temporal patterning and a neuronal subtype ratio similar to that of the developing human neocortex. This model was used to examine the effects of cocaine during neocorticogenesis. Cocaine caused premature neuronal differentiation and enhanced neurogenesis of various cortical neuronal subtypes. These cocaine-induced changes were inhibited by the cytochrome P450 inhibitor cimetidine. This in vitro model enables mechanistic studies of neocorticogenesis, and can be used to examine the mechanisms through which cocaine alters the development of the human neocortex. C1 [Kindberg, Abigail A.; Bendriem, Raphael M.; Spivak, Charles E.; Chen, Jia; Lupica, Carl R.; Freed, William J.; Lee, Chun-Ting] NIDA, Cellular Neurobiol Res Branch, Intramural Res Program, NIH,Dept Hlth & Human Serv, Baltimore, MD 21244 USA. [Handreck, Annelie] Univ Vet Med, Dept Pharmacol Toxicol & Pharm, D-30173 Hannover, Germany. [Liu, Jinny] US Naval Res Lab, Center Bio Mol Sci & Engn, Washington, DC 20375 USA. RP Lee, CT (reprint author), NIDA, Cellular Neurobiol Res Branch, Intramural Res Program, NIH,Dept Hlth & Human Serv, Baltimore, MD 21244 USA. EM clee@mail.nih.gov FU National Institute on Drug Abuse Intramural Research Program (NIDA IRP) FX This work was funded by the National Institute on Drug Abuse Intramural Research Program (NIDA IRP). NR 35 TC 3 Z9 3 U1 2 U2 20 PU COMPANY OF BIOLOGISTS LTD PI CAMBRIDGE PA BIDDER BUILDING CAMBRIDGE COMMERCIAL PARK COWLEY RD, CAMBRIDGE CB4 4DL, CAMBS, ENGLAND SN 1754-8403 EI 1754-8411 J9 DIS MODEL MECH JI Dis. Model. Mech. PD DEC PY 2014 VL 7 IS 12 BP 1397 EP 1405 DI 10.1242/dmm.017251 PG 9 WC Cell Biology; Pathology SC Cell Biology; Pathology GA AW2AL UT WOS:000346090500009 PM 25288682 ER PT J AU Chowell, G Blumberg, S Simonsen, L Miller, MA Viboud, C AF Chowell, Gerardo Blumberg, Seth Simonsen, Lone Miller, Mark A. Viboud, Cecile TI Synthesizing data and models for the spread of MERS-CoV, 2013: Key role of index cases and hospital transmission SO EPIDEMICS LA English DT Article DE Middle East respiratory syndrome; Reproduction number; Epidemic modeling; Index cases; Community; Hospital ID RESPIRATORY SYNDROME CORONAVIRUS; HONG-KONG; DROMEDARY CAMELS; SYNDROME SARS; SAUDI-ARABIA; INFECTIOUS-DISEASES; EPIDEMIC; OUTBREAK; SINGAPORE; DYNAMICS AB The outbreak of Middle East respiratory syndrome coronavirus (MERS-CoV) has caused 209 deaths and 699 laboratory-confirmed cases in the Arabian Peninsula as of June 11, 2014. Preparedness efforts are hampered by considerable uncertainty about the nature and intensity of human-to-human transmission, with previous reproduction number estimates ranging from 0.4 to 1.5. Here we synthesize epidemiological data and transmission models for the MERS-CoV outbreak during April-October 2013 to resolve uncertainties in epidemic risk, while considering the impact of observation bias. We match the progression of MERS-CoV cases in 2013 to a dynamic transmission model that incorporates community and hospital compartments, and distinguishes transmission by zoonotic (index) cases and secondary cases. When observation bias is assumed to account for the fact that all reported zoonotic cases are severe, but only similar to 57% of secondary cases are symptomatic, the average reproduction number of MERS-CoV is estimated to be 0.45 (95% CI: 0.29-0.61). Alternatively, if these epidemiological observations are taken at face value, index cases are estimated to transmit substantially more effectively than secondary cases, (R-i=0.84 (0.58-1.20) vs R-s=0.36 (0.24-0.51)). In both scenarios the relative contribution of hospital-based transmission is over four times higher than that of community transmission, indicating that disease control should be focused on hospitalized patients. Adjusting previously published estimates for observation bias confirms a strong support for the average R < 1 in the first stage of the outbreak in 2013 and thus, transmissibility of secondary cases of MERS-CoV remained well below the epidemic threshold. More information on the observation process is needed to clarify whether MERS-CoV is intrinsically weakly transmissible between people or whether existing control measures have contributed meaningfully to reducing the transmissibility of secondary cases. Our results could help evaluate the progression of MERS-CoV in recent months in response to changes in disease surveillance, control interventions, or viral adaptation. (C) 2014 The Authors. Published by Elsevier B.V. C1 [Chowell, Gerardo; Blumberg, Seth; Simonsen, Lone; Miller, Mark A.; Viboud, Cecile] NIH, Div Int Epidemiol & Populat Studies, Fogarty Int Ctr, Bethesda, MD 20892 USA. [Chowell, Gerardo] Arizona State Univ, Sch Human Evolut & Social Change, Ctr Global Hlth, Tempe, AZ USA. [Chowell, Gerardo] Arizona State Univ, Sch Human Evolut & Social Change, Math Computat & Modeling Sci Ctr, Tempe, AZ USA. [Blumberg, Seth] Univ Calif San Francisco, Francis I Proctor Fdn, San Francisco, CA 94143 USA. [Simonsen, Lone] George Washington Univ, Sch Publ Hlth & Hlth Serv, Dept Global Hlth, Washington, DC USA. RP Chowell, G (reprint author), Arizona State Univ, POB 872402, Tempe, AZ 85287 USA. EM gchowell@asu.edu OI Simonsen, Lone/0000-0003-1535-8526 FU RAPIDD program of the Science & Technology Directorate, Department of Homeland Security; Office of Global Affairs' International Influenza Unit in the Office of the Secretary of the Department of Health and Human Services; RAPIDD program of the Science and Technology Directorate, Department of Homeland Security; Fogarty International Center; National Institutes of Health; National Institute of Health MIDAS program (Modeling Infectious Disease Agent Study) [NIH NIGMS 1-U01-GM08778] FX This research was conducted in the context of the Multinational Influenza Seasonal Mortality Study (MISMS), an on-going international collaborative effort to understand influenza epidemiological and evolutionary patterns, led by the Fogarty International Center, National Institutes of Health (http://www.origem.info/misms/index.php). Funding for this project comes in part (LS) from the RAPIDD program of the Science & Technology Directorate, Department of Homeland Security, and from the Office of Global Affairs' International Influenza Unit in the Office of the Secretary of the Department of Health and Human Services. SB acknowledges financial support from RAPIDD program of the Science and Technology Directorate, Department of Homeland Security, the Fogarty International Center, National Institutes of Health, and the National Institute of Health MIDAS program (Modeling Infectious Disease Agent Study, grant number NIH NIGMS 1-U01-GM08778]. NR 52 TC 30 Z9 31 U1 6 U2 21 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 1755-4365 J9 EPIDEMICS-NETH JI Epidemics PD DEC PY 2014 VL 9 BP 40 EP 51 DI 10.1016/j.epidem.2014.09.011 PG 12 WC Infectious Diseases SC Infectious Diseases GA AW0TN UT WOS:000346006500005 PM 25480133 ER PT J AU Camacho, A Kucharski, AJ Funk, S Breman, J Piot, P Edmunds, WJ AF Camacho, A. Kucharski, A. J. Funk, S. Breman, J. Piot, P. Edmunds, W. J. TI Potential for large outbreaks of Ebola virus disease SO EPIDEMICS LA English DT Article DE Ebola; 1976 Zaire outbreak; Mathematical model; Basic reproduction number ID HEMORRHAGIC-FEVER; REPRODUCTIVE NUMBER; RISK-FACTORS; EPIDEMIC; UGANDA; CONGO; TRANSMISSION; INFERENCE; ZAIRE AB Outbreaks of Ebola virus can cause substantial morbidity and mortality in affected regions. The largest outbreak of Ebola to date is currently underway in West Africa, with 3944 cases reported as of 5th September 2014. To develop a better understanding of Ebola transmission dynamics, we revisited data from the first known Ebola outbreak, which occurred in 1976 in Zaire (now Democratic Republic of Congo). By fitting a mathematical model to time series stratified by disease onset, outcome and source of infection, we were able to estimate several epidemiological quantities that have previously proved challenging to measure, including the contribution of hospital and community infection to transmission. We found evidence that transmission decreased considerably before the closure of the hospital, suggesting that the decline of the outbreak was most likely the result of changes in host behaviour. Our analysis suggests that the person-to-person reproduction number was 1.34 (95% CI: 0.92-2.11) in the early part of the outbreak. Using stochastic simulations we demonstrate that the same epidemiological conditions that were present in 1976 could have generated a large outbreak purely by chance. At the same time, the relatively high person-to-person basic reproduction number suggests that Ebola would have been difficult to control through hospital-based infection control measures alone. (C) 2014 The Authors. Published by Elsevier B.V. C1 [Camacho, A.; Kucharski, A. J.; Funk, S.; Edmunds, W. J.] London Sch Hyg & Trop Med, Ctr Math Modelling Infect Dis, Dept Infect Dis Epidemiol, London WC1, England. [Breman, J.] NIH, Fogarty Int Ctr, Bethesda, MD USA. [Piot, P.] London Sch Hyg & Trop Med, London WC1, England. RP Camacho, A (reprint author), London Sch Hyg & Trop Med, Ctr Math Modelling Infect Dis, Dept Infect Dis Epidemiol, London WC1, England. EM anton.camacho@lshtm.ac.uk; adam.kucharski@lshtm.ac.uk FU Medical Research Council [MR/J01432X/1, MR/K021524/1, MR/K021680/1]; Region Ile-de-France through the scientific program DIM MALINF FX This work was supported by the Medical Research Council (AC, fellowship MR/J01432X/1; AJK, fellowship MR/K021524/1; SF, fellowship MR/K021680/1). We thank Prof. Bernard Cazelles for access to the computational resources used in this work, which were funded by an investment grant from the Region Ile-de-France through the scientific program DIM MALINF. NR 28 TC 32 Z9 34 U1 3 U2 71 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 1755-4365 J9 EPIDEMICS-NETH JI Epidemics PD DEC PY 2014 VL 9 BP 70 EP 78 DI 10.1016/j.epidem.2014.09.003 PG 9 WC Infectious Diseases SC Infectious Diseases GA AW0TN UT WOS:000346006500008 PM 25480136 ER PT J AU Robert, MA Okamoto, KW Gould, F Lloyd, AL AF Robert, Michael A. Okamoto, Kenichi W. Gould, Fred Lloyd, Alun L. TI Antipathogen genes and the replacement of disease-vectoring mosquito populations: a model-based evaluation SO EVOLUTIONARY APPLICATIONS LA English DT Article DE Aedes aegypti; antipathogen genes; dengue fever; female-killing; ordinary differential equation model; reduce and replace ID AEDES-AEGYPTI DIPTERA; GENETICALLY-MODIFIED MOSQUITOS; BORNE DISEASES; DENGUE TRANSMISSION; ENGINEERED UNDERDOMINANCE; INTRODUCING TRANSGENES; THEORETICAL-ANALYSIS; INSECT POPULATIONS; DENSITY-DEPENDENCE; AUTOCIDAL CONTROL AB Recently, genetic strategies aimed at controlling populations of disease-vectoring mosquitoes have received considerable attention as alternatives to traditional measures. Theoretical studies have shown that female-killing (FK), antipathogen (AP), and reduce and replace (R&R) strategies can each decrease the number competent vectors. In this study, we utilize a mathematical model to evaluate impacts on competent Aedes aegypti populations of FK, AP, and R&R releases as well as hybrid strategies that result from combinations of these three approaches. We show that while the ordering of efficacy of these strategies depends upon population life history parameters, sex ratio of releases, and switch time in combination strategies, AP-only and R&R/AP releases typically lead to the greatest long-term reduction in competent vectors. R&R-only releases are often less effective at long-term reduction of competent vectors than AP-only releases or R&R/AP releases. Furthermore, the reduction in competent vectors caused by AP-only releases is easier to maintain than that caused by FK-only or R&R-only releases even when the AP gene confers a fitness cost. We discuss the roles that density dependence and inclusion of females play in the order of efficacy of the strategies. We anticipate that our results will provide added impetus to continue developing AP strategies. C1 [Robert, Michael A.; Lloyd, Alun L.] N Carolina State Univ, Dept Math, Raleigh, NC 27695 USA. [Robert, Michael A.; Lloyd, Alun L.] N Carolina State Univ, Biomath Grad Program, Raleigh, NC 27695 USA. [Robert, Michael A.] Univ New Mexico, Dept Biol, Albuquerque, NM 87131 USA. [Robert, Michael A.] Univ New Mexico, Dept Math & Stat, Albuquerque, NM 87131 USA. [Okamoto, Kenichi W.; Gould, Fred] N Carolina State Univ, Dept Entomol, Raleigh, NC 27695 USA. [Gould, Fred; Lloyd, Alun L.] NIH, Fogarty Int Ctr, Bethesda, MD 20892 USA. RP Robert, MA (reprint author), Univ New Mexico, Dept Biol, Albuquerque, NM 87131 USA. EM marobert@unm.edu FU National Institutes of Health (NIH) [R01AI091980]; Foundation for the NIH through the Bill and Melinda Gates Foundation Grand Challenges in Global Health initiative; W.M. Keck Foundation; University of Pretoria-North Carolina State University Strategic Collaboration Seed Grant; Isaac Newton Institute for Mathematical Sciences, Cambridge, UK, as part of their Infectious Disease Dynamics program; NIH [U01GM097661] FX We are grateful to Tim Antonelli, Kevin Gross, and two anonymous reviewers for comments that improved the content of this paper. This work benefitted from discussion fostered by the Research and Policy for Infectious Disease Dynamics (RAPIDD) program of the Science and Technology Directory, Department of Homeland Security, and Fogarty International Center, NIH. This work was funded in part by National Institutes of Health (NIH) grant R01AI091980, a grant to the Regents of the University of California from the Foundation for the NIH through the Bill and Melinda Gates Foundation Grand Challenges in Global Health initiative and a grant from the W.M. Keck Foundation. A.L. Lloyd also acknowledges support from a University of Pretoria-North Carolina State University Strategic Collaboration Seed Grant and from the Isaac Newton Institute for Mathematical Sciences, Cambridge, UK, as part of their Infectious Disease Dynamics program (August-September 2013). M. A. Robert was also partially supported by NIH grant U01GM097661. NR 64 TC 1 Z9 2 U1 3 U2 24 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1752-4571 J9 EVOL APPL JI Evol. Appl. PD DEC PY 2014 VL 7 IS 10 BP 1238 EP 1251 DI 10.1111/eva.12219 PG 14 WC Evolutionary Biology SC Evolutionary Biology GA AW1WO UT WOS:000346079400008 PM 25558284 ER PT J AU Paix, A Wang, YM Smith, HE Lee, CYS Calidas, D Lu, T Smith, J Schmidt, H Krause, MW Seydoux, G AF Paix, Alexandre Wang, Yuemeng Smith, Harold E. Lee, Chih-Yung S. Calidas, Deepika Lu, Tu Smith, Jarrett Schmidt, Helen Krause, Michael W. Seydoux, Geraldine TI Scalable and Versatile Genome Editing Using Linear DNAs with Microhomology to Cas9 Sites in Caenorhabditis elegans SO GENETICS LA English DT Article ID HOMOLOGOUS RECOMBINATION; CRISPR-CAS; C-ELEGANS; DROSOPHILA; IMMUNITY; SYSTEMS AB Homology-directed repair (HDR) of double-strand DNA breaks is a promising method for genome editing, but is thought to be less efficient than error-prone nonhomologous end joining in most cell types. We have investigated HDR of double-strand breaks induced by CRISPR-associated protein 9 (Cas9) in Caenorhabditis elegans. We find that HDR is very robust in the C. elegans germline. Linear repair templates with short (similar to 30-60 bases) homology arms support the integration of base and gene-sized edits with high efficiency, bypassing the need for selection. Based on these findings, we developed a systematic method to mutate, tag, or delete any gene in the C. elegans genome without the use of co-integrated markers or long homology arms. We generated 23 unique edits at 11 genes, including premature stops, whole-gene deletions, and protein fusions to antigenic peptides and GFP. Whole-genome sequencing of five edited strains revealed the presence of passenger variants, but no mutations at predicted off-target sites. The method is scalable for multi-gene editing projects and could be applied to other animals with an accessible germline. C1 [Paix, Alexandre; Wang, Yuemeng; Lee, Chih-Yung S.; Calidas, Deepika; Lu, Tu; Smith, Jarrett; Schmidt, Helen; Seydoux, Geraldine] Johns Hopkins Univ, Sch Med, Dept Mol Biol & Genet, Baltimore, MD 21205 USA. [Smith, Harold E.; Krause, Michael W.] NIDDK, NIH, Bethesda, MD 20892 USA. RP Seydoux, G (reprint author), Johns Hopkins Univ, Sch Med, Dept Mol Biol & Genet, PCTB 706, Baltimore, MD 21205 USA. EM gseydoux@jhmi.edu RI Paix, Alexandre/E-9137-2011; OI Wang, Yuemeng/0000-0003-3928-6926; Paix, Alexandre/0000-0002-8080-7546; Seydoux, Geraldine/0000-0001-8257-0493; Krause, Michael/0000-0001-6127-3940; Schmidt, Helen/0000-0002-3449-2790 FU National Institutes of Health (NIH) [R01HD37047]; Intramural Research Program of the NIH; National Institute of Diabetes and Digestive and Kidney Diseases FX We thank Craig Mello for sharing results prior to publication, Mario de Bono for reagents, Bram Lambrus for sgRNA cloning assistance, Dominique Rasoloson for strain archival, and Andrew Folkmann and Dan Dickinson for discussion and comments on the manuscript. This work was supported by National Institutes of Health (NIH) grant R01HD37047, by the Intramural Research Program of the NIH, and the National Institute of Diabetes and Digestive and Kidney Diseases. G.S. is an investigator of the Howard Hughes Medical Institute. NR 27 TC 50 Z9 51 U1 2 U2 21 PU GENETICS SOCIETY AMERICA PI BETHESDA PA 9650 ROCKVILLE AVE, BETHESDA, MD 20814 USA SN 0016-6731 EI 1943-2631 J9 GENETICS JI Genetics PD DEC PY 2014 VL 198 IS 4 BP 1347 EP + DI 10.1534/genetics.114.170423 PG 25 WC Genetics & Heredity SC Genetics & Heredity GA AW1OQ UT WOS:000346059300001 PM 25249454 ER PT J AU Teutsch, SM Fielding, JE Khoury, MJ Evans, JP AF Teutsch, Steven M. Fielding, Jonathan E. Khoury, Muin J. Evans, James P. TI Utility before business SO GENETICS IN MEDICINE LA English DT Editorial Material ID MEDICINE; COST C1 [Teutsch, Steven M.; Fielding, Jonathan E.] Dept Publ Hlth, Los Angeles, CA 90082 USA. [Fielding, Jonathan E.] Univ Calif Los Angeles, Fielding Sch Publ Hlth, Los Angeles, CA USA. [Fielding, Jonathan E.] Univ Calif Los Angeles, Sch Med, Los Angeles, CA USA. [Khoury, Muin J.] Ctr Dis Control & Prevent, Off Publ Hlth Genom, Atlanta, GA USA. [Khoury, Muin J.] NIH, Epidemiol & Genom Res Program, Bethesda, MD 20892 USA. [Evans, James P.] Univ N Carolina, Sch Med, Chapel Hill, NC USA. RP Teutsch, SM (reprint author), Dept Publ Hlth, Los Angeles, CA 90082 USA. EM steventeutsch@gmail.com; jfielding@ph.lacounty.gov FU Intramural CDC HHS [CC999999]; NHGRI NIH HHS [U01 HG006487] NR 12 TC 2 Z9 2 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1098-3600 EI 1530-0366 J9 GENET MED JI Genet. Med. PD DEC PY 2014 VL 16 IS 12 BP 869 EP 870 DI 10.1038/gim.2014.71 PG 2 WC Genetics & Heredity SC Genetics & Heredity GA AW1HN UT WOS:000346040900002 PM 25010054 ER PT J AU Feero, WG Manolio, TA Khoury, MJ AF Feero, W. Gregory Manolio, Teri A. Khoury, Muin J. TI Translational research is a key to nongeneticist physicians' genomics education SO GENETICS IN MEDICINE LA English DT Editorial Material ID GENETICS C1 [Feero, W. Gregory] Maine Dartmouth Family Med Residency Program, Augusta, ME 04332 USA. [Manolio, Teri A.] NHGRI, Div Genom Med, NIH, Bethesda, MD 20892 USA. [Khoury, Muin J.] Ctr Dis Control & Prevent, Off Publ Hlth Genom, Atlanta, GA USA. [Khoury, Muin J.] NCI, Epidemiol & Genom Res Program, Div Canc Control & Populat Sci, NIH, Rockville, MD USA. RP Feero, WG (reprint author), Maine Dartmouth Family Med Residency Program, Augusta, ME 04332 USA. EM wfeero@mainegeneral.org FU Intramural CDC HHS [CC999999] NR 8 TC 10 Z9 10 U1 0 U2 3 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1098-3600 EI 1530-0366 J9 GENET MED JI Genet. Med. PD DEC PY 2014 VL 16 IS 12 BP 871 EP 873 DI 10.1038/gim.2014.67 PG 3 WC Genetics & Heredity SC Genetics & Heredity GA AW1HN UT WOS:000346040900003 PM 24875299 ER PT J AU Biesecker, BB Klein, W Lewis, KL Fisher, TC Wright, MF Biesecker, LG Han, PK AF Biesecker, Barbara B. Klein, William Lewis, Katie L. Fisher, Tyler C. Wright, Martha Frances Biesecker, Leslie G. Han, Paul K. TI How do research participants perceive "uncertainty" in genome sequencing? SO GENETICS IN MEDICINE LA English DT Article DE epistemological beliefs; expectations; genome sequencing; informed choice; uncertainty ID DECISION-MAKING; CHILDREN; CLINSEQ AB Purpose: The scope of uncertainty in genome sequence information has no rival in health-care delivery. We present data from adults participating in a National Institutes of Health study using this technology, in which perceptions of uncertainty are hypothesized to be key in predicting decisions to learn and act on genome health information. Methods: We conducted six professionally moderated focus groups with 39 randomly selected ClinSeq participants varying on whether they had coronary heart disease and had received prior sequence results. We elicited perceptions of the uncertainties associated with genome sequencing using written prompts. Results: Participants perceived uncertainty as a quality of genome information. The majority of participants characterized uncertainty of sequencing information as "changing, fluid, developing, or ground breaking" These responses led to anticipation of more optimistic future outcomes. Fewer participants described uncertainty as, "questionable; less accurate, limited, or poorly understood." These; perceptions seemed to undermine participants' faith in genome information, leading to feelings of disillusionment. Conclusion: Our findings suggest that perceptions Of uncertainty are related to epistemological beliefs that inform expectations for the information. Interventions that promote realistic expectations of genome sequencing may mitigate negative responses to uncertainty. C1 [Biesecker, Barbara B.; Fisher, Tyler C.] NHGRI, Social & Behav Res Branch, NIH, Bethesda, MD 20892 USA. [Klein, William] NCI, Div Canc Control & Populat Sci, NIH, Bethesda, MD 20892 USA. [Lewis, Katie L.; Wright, Martha Frances; Biesecker, Leslie G.] NHGRI, Genet Dis Res Branch, NIH, Bethesda, MD 20892 USA. [Han, Paul K.] Ctr Outcomes Res & Evaluat, Maine Med Ctr, Res Inst, Scarborough, ME USA. RP Biesecker, BB (reprint author), NHGRI, Social & Behav Res Branch, NIH, Bethesda, MD 20892 USA. EM barbarab@mail.nih.gov OI Han, Paul/0000-0003-0165-1940 FU National Human Genome Research Institute, National Institutes of Health FX We thank the focus group participants; Chanza Baytop and Barbara Rosenthal for moderating the groups; and Chris Anderson for help with the references. The Intramural Research Program of the National Human Genome Research Institute, National Institutes of Health, funded this research. NR 15 TC 9 Z9 9 U1 2 U2 3 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1098-3600 EI 1530-0366 J9 GENET MED JI Genet. Med. PD DEC PY 2014 VL 16 IS 12 BP 977 EP 980 DI 10.1038/gim.2014.57 PG 4 WC Genetics & Heredity SC Genetics & Heredity GA AW1HN UT WOS:000346040900017 PM 24875302 ER PT J AU Lin, HH Joehanes, R Pilling, LC Dupuis, J Lunetta, KL Ying, SX Benjamin, EJ Hernandez, D Singleton, A Melzer, D Munson, PJ Levy, D Ferrucci, L Murabito, JM AF Lin, Honghuang Joehanes, Roby Pilling, Luke C. Dupuis, Josee Lunetta, Kathryn L. Ying, Sai-Xia Benjamin, Emelia J. Hernandez, Dena Singleton, Andrew Melzer, David Munson, Peter J. Levy, Daniel Ferrucci, Luigi Murabito, Joanne M. TI Whole blood gene expression and interleukin-6 levels SO GENOMICS LA English DT Article DE Inflammation; Gene expression; Interleukin-6; Epidemiology ID CORONARY-HEART-DISEASE; C-REACTIVE PROTEIN; FRAIL MOUSE MODEL; ANDROGEN RECEPTOR; INFLAMMATORY BIOMARKERS; OLDER PERSONS; FRAMINGHAM; CELLS; RISK; AGE AB Background: Circulating interleukin-6 levels increase with advancing age and are a risk factor for various diseases and mortality. The characterization of gene expression profiles associated with interleukin-6 levels might suggest important molecular events underlying its regulation. Methods and results: We studied the association of transcriptional profiles with interleukin-6 levels in 2422 participants from the Framingham Heart Study Offspring Cohort using Affymetrix Human Exon 1.0 ST Array. We identified 4139 genes that were significantly associated with interleukin-6 levels (FDR < 0.05) after adjusting for age, sex and blood cell components. We then replicated 807 genes in the InCHIANTI study with 694 participants. Many of the top genes are involved in inflammation-related pathways or erythrocyte function, including JAK/Stat signaling pathway and interleukin-10 signaling pathway. Conclusion: We identified and replicated 807 genes that were associated with circulating interleukin-6 levels. Future characterization of interleukin-6 regulation networks may facilitate the identification of additional potential targets for treating inflammation-related diseases. (C) 2014 Elsevier Inc. All rights reserved. C1 [Lin, Honghuang] Boston Univ, Sch Med, Dept Med, Sect Computat Biomed, Boston, MA 02118 USA. [Lin, Honghuang; Joehanes, Roby; Dupuis, Josee; Lunetta, Kathryn L.; Benjamin, Emelia J.; Munson, Peter J.; Levy, Daniel; Murabito, Joanne M.] NHLBI, Framingham, MA USA. [Lin, Honghuang; Joehanes, Roby; Dupuis, Josee; Lunetta, Kathryn L.; Benjamin, Emelia J.; Munson, Peter J.; Levy, Daniel; Murabito, Joanne M.] Boston Univ, Framingham Heart Study, Framingham, MA USA. [Joehanes, Roby; Ying, Sai-Xia; Munson, Peter J.] NIH, Ctr Informat Technol, Math & Stat Comp Lab, Bethesda, MD 20892 USA. [Joehanes, Roby; Munson, Peter J.; Levy, Daniel] NHLBI, Populat Sci Branch, Bethesda, MD 20892 USA. [Pilling, Luke C.; Melzer, David] Univ Exeter, Sch Med, Exeter EX1 2LU, Devon, England. NIA, Neurogenet Lab, NIH, Bethesda, MD 20892 USA. [Dupuis, Josee; Lunetta, Kathryn L.] Boston Univ, Sch Publ Hlth, Dept Biostat, Boston, MA USA. [Benjamin, Emelia J.] Boston Univ, Sch Med, Dept Med, Sect Cardiovasc Med & Prevent Med, Boston, MA 02118 USA. [Benjamin, Emelia J.] Boston Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA USA. [Ferrucci, Luigi] NIA, Clin Res Branch, Baltimore, MD 21224 USA. [Murabito, Joanne M.] Boston Univ, Sch Med, Dept Med, Gen Internal Med Sect, Boston, MA 02118 USA. RP Lin, HH (reprint author), Boston Univ, Sch Med, Dept Med, Sect Computat Biomed, 72 East Concord St,B-616, Boston, MA 02118 USA. EM hhlin@bu.edu; murabito@bu.edu RI Singleton, Andrew/C-3010-2009; OI Pilling, Luke/0000-0002-3332-8454; Lin, Honghuang/0000-0003-3043-3942; Benjamin, Emelia/0000-0003-4076-2336; Melzer, David/0000-0002-0170-3838 FU Division of Intramural Research; National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD.; NIH [1R01 HL64753, R01AG028321, R01AG029451]; Intramural Research Program, National Institute on Aging (Ferrucci); Wellcome Trust grant; plus internal medical school funding (Melzer); National Heart, Lung, and Blood Institute [N01-HC-25195]; [R01 HL 064753]; [R01 HL076784] FX FHS gene expression profiling was funded through the Division of Intramural Research (Principal Investigator, Daniel Levy), National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD. Measurement of interleukin-6 was funded through R01 HL 064753 and R01 HL076784. This work is supported by NIH grants 1R01 HL64753 (Benjamin), R01AG028321 (Benjamin), and R01AG029451 (Murabito). This study was supported in part by the Intramural Research Program, National Institute on Aging (Ferrucci). UK based work was supported by a Wellcome Trust grant to the University of Exeter, plus internal medical school funding (Melzer). The Framingham Heart Study is supported by the National Heart, Lung, and Blood Institute contract N01-HC-25195. NR 61 TC 5 Z9 5 U1 0 U2 3 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0888-7543 EI 1089-8646 J9 GENOMICS JI Genomics PD DEC PY 2014 VL 104 IS 6 BP 490 EP 495 DI 10.1016/j.ygeno.2014.10.003 PN B PG 6 WC Biotechnology & Applied Microbiology; Genetics & Heredity SC Biotechnology & Applied Microbiology; Genetics & Heredity GA AW1OT UT WOS:000346059600007 PM 25311648 ER PT J AU Marangoni, D Wu, ZJ Wiley, HE Zeiss, CJ Vijayasarathy, C Zeng, Y Hiriyanna, S Bush, RA Wei, LL Colosi, P Sieving, PA AF Marangoni, Dario Wu, Zhijian Wiley, Henry E. Zeiss, Caroline J. Vijayasarathy, Camasamudram Zeng, Yong Hiriyanna, Suja Bush, Ronald A. Wei, Lisa L. Colosi, Peter Sieving, Paul A. TI Preclinical Safety Evaluation of a Recombinant AAV8 Vector for X-Linked Retinoschisis After Intravitreal Administration in Rabbits SO HUMAN GENE THERAPY CLINICAL DEVELOPMENT LA English DT Article ID HUMAN GENE-THERAPY; LEBERS CONGENITAL AMAUROSIS; RETINAL TOXICITY; CLINICAL-TRIAL; DELIVERY; TRIAMCINOLONE; TRANSDUCTION; EXPRESSION; KNOCKOUT; EFFICACY AB X-linked retinoschisis (XLRS) is a retinal disease caused by mutations in the gene encoding the protein retinoschisin (RS1) and one of the most common causes of macular degeneration in young men. Currently, no FDA-approved treatments are available for XLRS and a replacement gene therapy could provide a promising strategy. We have developed a novel gene therapy approach for XLRS, based on the administration of AAV8-scRS/IRBPhRS, an adeno-associated viral vector coding the human RS1 protein, via the intravitreal route. On the basis of our prior study in an Rs1-KO mouse, this construct transduces efficiently all the retinal layers, resulting in an RS1 expression similar to that observed in the wild-type and improving retinal structure and function. In support of a clinical trial, we carried out a study to evaluate the ocular safety of intravitreal administration of AAV8-scRS/IRBPhRS into 39 New Zealand White rabbits. Two dose levels of vector, 2e(10) and 2e(11) vector genomes per eye (vg/eye), were tested and ocular inflammation was monitored over a 12-week period by serial ophthalmological and histopathological analysis. A mild ocular inflammatory reaction, consisting mainly of vitreous infiltrates, was observed within 4 weeks from injection, in both 2e(10) and 2e(11) vg/eye groups and was likely driven by the AAV8 capsid. At 12-week follow-up, ophthalmological examination revealed no clinical signs of vitreitis in either of the dose groups. However, while vitreous inflammatory infiltrate was significantly reduced in the 2e(10) vg/eye group at 12 weeks, some rabbits in the higher dose group still showed persistence of inflammatory cells, histologically. In conclusion, intravitreal administration of AAV8-scRS/IRBPhRS into the rabbit eye produces a mild and transient intraocular inflammation that resolves, at a 2e(10) vg/eye dose, within 3 months, and does not cause irreversible tissue damages. These data support the initiation of a clinical trial of intravitreal administration of AAV8-scRS/IRBPhRS in XLRS patients. C1 [Marangoni, Dario; Vijayasarathy, Camasamudram; Zeng, Yong; Bush, Ronald A.; Sieving, Paul A.] Natl Inst Deafness & Other Commun Disorders, NIH, Bethesda, MD 20892 USA. [Wu, Zhijian; Wiley, Henry E.; Hiriyanna, Suja; Wei, Lisa L.; Colosi, Peter; Sieving, Paul A.] NEI, NIH, Bethesda, MD 20892 USA. [Marangoni, Dario] Univ Aquila, Dept Biotechnol & Appl Clin Sci, I-67100 Laquila, Italy. [Zeiss, Caroline J.] Yale Univ, Sch Med, Comparat Med Sect, New Haven, CT 06520 USA. RP Sieving, PA (reprint author), NEI, NIH, 31 Ctr Dr,Room 6A03, Bethesda, MD 20892 USA. EM pas@nei.nih.gov FU National Institutes of Health, National Institute on Deafness and Other Communication Disorders; National Eye Institute FX This work was supported by the Intramural Research Program of the National Institutes of Health, National Institute on Deafness and Other Communication Disorders, and the National Eye Institute. NR 41 TC 6 Z9 7 U1 0 U2 7 PU MARY ANN LIEBERT, INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 2324-8637 EI 2324-8645 J9 HUM GENE THER CL DEV JI Hum. Gene Ther. Clin. Dev. PD DEC 1 PY 2014 VL 25 IS 4 BP 202 EP 211 DI 10.1089/humc.2014.067 PG 10 WC Biotechnology & Applied Microbiology; Critical Care Medicine; Medicine, Research & Experimental SC Biotechnology & Applied Microbiology; General & Internal Medicine; Research & Experimental Medicine GA AW5TG UT WOS:000346336100002 PM 25211193 ER PT J AU Nagaraja, N Warach, S Hsia, AW Adams, HP Auh, S Latour, LL Merino, JG AF Nagaraja, Nandakumar Warach, Steven Hsia, Amie W. Adams, Harold P., Jr. Auh, Sungyoung Latour, Lawrence L. Merino, Jose G. TI Association Between Neurologic Improvement With Decline in Blood Pressure and Recanalization in Stroke SO JAMA NEUROLOGY LA English DT Article ID VENTRICULAR RESPONSE; ATRIAL-FIBRILLATION; ISCHEMIC-STROKE; THROMBOLYSIS AB IMPORTANCE Patients with stroke often have a decline in blood pressure after thrombolysis. Neurologic improvement could result from recanalization or better collateral flow despite persistent occlusion. We hypothesized that neurologic improvement with concurrent decline in blood pressure may be a clinical sign of recanalization after intravenous tissue plasminogen activator. OBSERVATIONS Patients treated with intravenous tissue plasminogen activator at Suburban Hospital, Bethesda, Maryland, and MedStar Washington Hospital Center, Washington, DC, from 1999 to 2009 were included in the study if they had pretreatment and 24-hour magnetic resonance angiographic scans, National Institutes of Health Stroke Scale scores at those times, and proximal middle cerebral artery occlusion demonstrated prior to treatment. The recanalization status on 24-hour magnetic resonance angiography was classified as none, partial, or complete. Seventeen patients met study criteria. On 24-hour magnetic resonance angiography, 3 patients had no recanalization, 8 had partial recanalization, and 6 had complete recanalization. At 24 hours after thrombolysis, neurologic improvement with concurrent decline in systolic blood pressure of 20 mm Hg or greater was seen in 4 patients with partial recanalization, 4 patients with complete recanalization, and none of the patients with no recanalization. CONCLUSIONS AND RELEVANCE Neurologic improvement with concurrent decline in systolic blood pressure of 20 mm Hg or greater after intravenous tissue plasminogen activator may be a clinical sign of recanalization. This observation needs confirmation in a larger cohort. C1 [Nagaraja, Nandakumar; Hsia, Amie W.; Latour, Lawrence L.; Merino, Jose G.] NINDS, Stroke Diagnost & Therapeut Sect, Bethesda, MD 20892 USA. [Nagaraja, Nandakumar; Adams, Harold P., Jr.] Univ Iowa, Iowa City, IA 52242 USA. [Warach, Steven] Univ Texas SW Med Ctr, Austin, TX USA. [Hsia, Amie W.] MedStar Washington Hosp Ctr, Washington, DC USA. [Auh, Sungyoung] NINDS, Bethesda, MD 20892 USA. [Merino, Jose G.] Johns Hopkins Community Phys, Bethesda, MD USA. RP Nagaraja, N (reprint author), Univ Iowa, 200 Hawkins Dr,2149 RCP, Iowa City, IA 52242 USA. EM nandakumar-nagaraja@uiowa.edu OI Merino, Jose/0000-0002-6676-0008 FU Intramural Research Program of the National Institutes of Health, National Institute of Neurological Disorders and Stroke; National Institute of Neurological Disorders and Stroke FX This research was supported by the Intramural Research Program of the National Institutes of Health, National Institute of Neurological Disorders and Stroke. Dr Adams has grant support from the National Institute of Neurological Disorders and Stroke. NR 6 TC 3 Z9 4 U1 0 U2 2 PU AMER MEDICAL ASSOC PI CHICAGO PA 330 N WABASH AVE, STE 39300, CHICAGO, IL 60611-5885 USA SN 2168-6149 EI 2168-6157 J9 JAMA NEUROL JI JAMA Neurol. PD DEC PY 2014 VL 71 IS 12 BP 1555 EP 1558 DI 10.1001/jamaneurol.2014.2036 PG 4 WC Clinical Neurology SC Neurosciences & Neurology GA AW1YA UT WOS:000346083500015 PM 25330362 ER PT J AU Pandey, S Byler, DL Hallett, M AF Pandey, Sanjay Byler, Debra L. Hallett, Mark TI HemidystoniaWith One Eye-of-the-Tiger Sign SO JAMA NEUROLOGY LA English DT Editorial Material C1 [Pandey, Sanjay; Hallett, Mark] NINDS, Human Motor Control Sect, NIH, Bethesda, MD 20892 USA. [Pandey, Sanjay] Govind Ballabh Pant Hosp, Dept Neurol, New Delhi, India. [Byler, Debra L.] Penn State Coll Med, Dept Neurol, Hershey, PA USA. [Byler, Debra L.] Penn State Coll Med, Dept Pediat, Hershey, PA USA. RP Hallett, M (reprint author), NINDS, Human Motor Control Sect, NIH, 10 Ctr Dr,MSC 1428,Bldg 10,Room 7D37, Bethesda, MD 20892 USA. EM hallettm@ninds.nih.gov FU Intramural NIH HHS NR 3 TC 2 Z9 2 U1 0 U2 0 PU AMER MEDICAL ASSOC PI CHICAGO PA 330 N WABASH AVE, STE 39300, CHICAGO, IL 60611-5885 USA SN 2168-6149 EI 2168-6157 J9 JAMA NEUROL JI JAMA Neurol. PD DEC PY 2014 VL 71 IS 12 BP 1574 EP 1575 DI 10.1001/jamaneurol.2014.1077 PG 2 WC Clinical Neurology SC Neurosciences & Neurology GA AW1YA UT WOS:000346083500019 PM 25347119 ER PT J AU Janssen, E Morbach, H Ullas, S Bannock, JM Massad, C Menard, L Barlan, I Lefranc, G Su, H Dasouki, M Al-Herz, W Keles, S Chatila, T Geha, RS Meffre, E AF Janssen, Erin Morbach, Henner Ullas, Sumana Bannock, Jason M. Massad, Christopher Menard, Laurence Barlan, Isil Lefranc, Gerard Su, Helen Dasouki, Majed Al-Herz, Waleed Keles, Sevgi Chatila, Talal Geha, Raif S. Meffre, Eric TI Dedicator of cytokinesis 8-deficient patients have a breakdown in peripheral B-cell tolerance and defective regulatory T cells SO JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY LA English DT Article DE Dedicator of cytokinesis 8; autoimmunity; B-cell tolerance; regulatory T cells ID HYPER-IGE SYNDROME; DOCK8 DEFICIENCY; AUTOANTIBODY PRODUCTION; TRANSPLANTATION; HUMANS; ACTIVATION; EXPRESSION; MUTATIONS; LIGAND; LUPUS AB Background: Dedicator of cytokinesis 8 (DOCK8) deficiency is typified by recurrent infections, increased serum IgE levels, eosinophilia, and a high incidence of allergic and autoimmune manifestations. Objective: We sought to determine the role of DOCK8 in the establishment and maintenance of human B-cell tolerance. Methods: Autoantibodies were measured in the plasma of DOCK8-deficient patients. The antibody-coding genes from new emigrant/transitional and mature naive B cells were cloned and assessed for their ability to bind self-antigens. RegulatoryT(Treg) cells in the blood were analyzed by means of flow cytometry, and their function was tested by examining their capacity to inhibit the proliferation of CD4(+)CD25(-) effector T cells. Results: DOCK8-deficient patients had increased levels of autoantibodies in their plasma. We determined that central B-cell tolerance did not require DOCK8, as evidenced by the normally low frequency of polyreactive new emigrant/transitional B cells in DOCK8-deficient patients. In contrast, autoreactive B cells were enriched in the mature naive B-cell compartment, revealing a defective peripheral B-cell tolerance checkpoint. In addition, we found that Treg cells were decreased and exhibited impaired suppressive activity in DOCK8-deficient patients. Conclusions: Our data support a critical role for DOCK8 in Treg cell homeostasis and function and the enforcement of peripheral B-cell tolerance. C1 [Janssen, Erin; Ullas, Sumana; Keles, Sevgi; Chatila, Talal; Geha, Raif S.] Boston Childrens Hosp, Div Immunol, Boston, MA 02115 USA. [Janssen, Erin; Chatila, Talal; Geha, Raif S.] Harvard Univ, Sch Med, Dept Pediat, Boston, MA 02115 USA. [Morbach, Henner; Bannock, Jason M.; Massad, Christopher; Menard, Laurence; Meffre, Eric] Yale Univ, Sch Med, Dept Immunobiol, New Haven, CT USA. [Barlan, Isil] Marmara Univ, Istanbul, Turkey. [Lefranc, Gerard] Univ Montpellier, IMGT, F-34059 Montpellier, France. [Lefranc, Gerard] CNRS, Inst Human Genet, Montpellier, France. [Su, Helen] NIH, Human Immunol Dis Unit, Bethesda, MD 20892 USA. [Dasouki, Majed] Univ Kansas, Med Ctr, Div Genet Endocrinol & Metab, Dept Pediat, Kansas City, MO USA. [Dasouki, Majed] Univ Kansas, Med Ctr, Div Genet Endocrinol & Metab, Dept Internal Med, Kansas City, MO USA. [Al-Herz, Waleed] Kuwait Univ, Fac Med, Dept Pediat, Safat 13060, Kuwait. [Keles, Sevgi] Necmettin Erbakan Univ, Meram Med Fac, Div Pediat Immunol & Allergy, Konya, Turkey. RP Geha, RS (reprint author), Boston Childrens Hosp, One Blackfan St, Boston, MA 02115 USA. EM raif.geha@childrens.harvard.edu; eric.meffre@yale.edu RI Su, Helen/H-9541-2015 OI Su, Helen/0000-0002-5582-9110 FU National Institutes of Health (NIH)/National Institute of Allergy and Infectious Diseases (NIAID) [AI061093, AI071087, AI082713, AI095848, AI100315, HL059561, 5K 12HD052896]; Manton Foundation; German Research Foundation [DFG MO2160/2-1]; Dubai-Harvard Foundation for Medical Research; Jeffrey Modell Foundation; Intramural Research Program of the NIH; NIAID; Kuwait Foundation for the Advancement of Sciences [2010-1302-05] FX Supported by National Institutes of Health (NIH)/National Institute of Allergy and Infectious Diseases (NIAID) grants AI061093, AI071087, AI082713, and AI095848 (to E.M.); AI100315 and HL059561 (to R.S.G.); and 5K 12HD052896 (to E.J.), as well as by grants from the Manton Foundation (to E.J.), German Research Foundation grant DFG MO2160/2-1 (to H.M.), the Dubai-Harvard Foundation for Medical Research and the Jeffrey Modell Foundation (to R.S.G.), the Intramural Research Program of the NIH, NIAID (to H.S.), and the Kuwait Foundation for the Advancement of Sciences 2010-1302-05 (to W.A.-H.). NR 48 TC 22 Z9 22 U1 0 U2 8 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0091-6749 EI 1097-6825 J9 J ALLERGY CLIN IMMUN JI J. Allergy Clin. Immunol. PD DEC PY 2014 VL 134 IS 6 BP 1365 EP 1374 DI 10.1016/j.jaci.2014.07.042 PG 10 WC Allergy; Immunology SC Allergy; Immunology GA AW1UG UT WOS:000346075400019 PM 25218284 ER PT J AU Cookson, MR AF Cookson, Mark R. TI Lardy brains make Parkinson's disease mice worse SO JOURNAL OF NEUROCHEMISTRY LA English DT Editorial Material AB Read the full article Diet-induced obesity accelerates the onset of terminal phenotypes in -synuclein transgenic mice' on page 848. C1 NIA, Cell Biol & Gene Express Sect, Neurogenet Lab, NIH, Bethesda, MD 20892 USA. RP Cookson, MR (reprint author), NIA, Cell Biol & Gene Express Sect, Neurogenet Lab, NIH, Bethesda, MD 20892 USA. EM cookson@mail.nih.gov FU Intramural NIH HHS [ZIA AG000939-07] NR 7 TC 1 Z9 1 U1 0 U2 1 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0022-3042 EI 1471-4159 J9 J NEUROCHEM JI J. Neurochem. PD DEC PY 2014 VL 131 IS 6 BP 697 EP 698 DI 10.1111/jnc.12843 PG 2 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA AW2ZX UT WOS:000346156200001 PM 25142063 ER PT J AU Shpyleva, S Pogribna, M Cozart, C Bryant, MS Muskhelishvili, L Tryndyak, VP Ross, SA Beland, FA Pogribny, IP AF Shpyleva, Svitlana Pogribna, Marta Cozart, Christy Bryant, Matthew S. Muskhelishvili, Levan Tryndyak, Volodymyr P. Ross, Sharon A. Beland, Frederick A. Pogribny, Igor P. TI Interstrain differences in the progression of nonalcoholic steatohepatitis to fibrosis in mice are associated with altered hepatic iron metabolism SO JOURNAL OF NUTRITIONAL BIOCHEMISTRY LA English DT Article DE NAFLD; Methyl-deficient diet; Liver fibrogenesis; Iron metabolism; IRP1; miR-200a ID FATTY LIVER-DISEASE; FOLATE-DEFICIENT DIET; ENDOPLASMIC-RETICULUM STRESS; REGULATORY PROTEINS; LIPID-METABOLISM; OXIDATIVE STRESS; STELLATE CELLS; FERRITIN; CHOLINE; INJURY AB Nonalcoholic fatty liver disease (NAFLD) is a major health problem worldwide. Currently, there is a lack of conclusive information to clarify the molecular events and mechanisms responsible for the progression of NAFLD to fibrosis and cirrhosis and, more importantly, for differences in interindividual disease severity. The aim of this study was to investigate a role of interindividual differences in iron metabolism among inbred mouse strains in the pathogenesis and severity of fibrosis in a model of NAFLD. Feeding male A/J, 129S1/SvImJ and WSB/EiJ mice a choline- and folate-deficient diet caused NAFLD-associated liver injury and iron metabolism abnormalities, especially in WSB/EiJ mice. NAFLD-associated fibrogenesis was correlated with a marked strain- and injury-dependent increase in the expression of iron metabolism genes, especially transferrin receptor (Tfrc), ferritin heavy chain (Fth1), and solute carrier family 40 (iron-regulated transporter), member 1 (Slc40a1, Fpn1) and their related proteins, and pronounced down-regulation of the iron regulatory protein 1 (IRP1), with the magnitude being A/J<129S1/SvImJ 1.5, whereas this was seen in none of the controls (p < 0.0001). At time of the first positive qPCR for JCV DNA, 11 of 20 (55%) patients with natalizumab-associated PML had an AI(JCV) > 1.5. JCV DNA levels of <100 copies/ml were seen in 14 (70%) of these 20 patients, of whom 8 (57%) demonstrated an AI(JCV) > 1.5. InterpretationDetermination of the AI(JCV) could be an added tool in the diagnostic workup for PML and should be included in the case definition of natalizumab-associated PML. Ann Neurol 2014;76:792-801 C1 [Warnke, Clemens; Dehmel, Thomas; Hartung, Hans-Peter; Kieseier, Bernd C.] Univ Dusseldorf, Dept Neurol, Fac Med, D-40225 Dusseldorf, Germany. [von Geldern, Gloria; Major, Eugene] NINDS, NIH, Bethesda, MD 20892 USA. [Markwerth, Philipp; Adams, Ortwin] Univ Dusseldorf, Inst Virol, D-40225 Dusseldorf, Germany. [Hoepner, Robert; Gold, Ralf] Ruhr Univ Bochum, Dept Neurol, Bochum, Germany. [Pawlita, Michael] German Canc Res Ctr, Res Program Infect & Canc, Heidelberg, Germany. [Kuempfel, Tania; Hohlfeld, Reinhard] Univ Munich, Inst Clin Neuroimmunol, Munich, Germany. [Kuempfel, Tania; Hohlfeld, Reinhard] Munich Cluster Syst Neurol SyNergy, Munich, Germany. [Maeurer, Mathias] Caritas Hosp, Dept Neurol, Bad Mergentheim, Germany. [Stangel, Martin; Wegner, Florian] Hannover Med Sch, Dept Neurol, Hannover, Germany. [Straeten, Vera] Johannes Wesling Hosp Minden, Dept Neurol, Minden, Germany. [Limmroth, Volker] Merheim Hosp, Dept Neurol, Cologne, Germany. [Weber, Thomas] Marienhosp Hamburg, Dept Neurol, Hamburg, Germany. [Hermsen, Derik] Univ Hosp Dusseldorf, Inst Clin Chem & Lab Diagnost, Dusseldorf, Germany. [Kleinschnitz, Christoph] Univ Wurzburg, Dept Neurol, Wurzburg, Germany. [Wattjes, Mike P.] Vrije Univ Amsterdam, Med Ctr, MS Ctr Amsterdam, Amsterdam, Netherlands. [Wattjes, Mike P.] Vrije Univ Amsterdam, Med Ctr, Dept Radiol, Amsterdam, Netherlands. [Svenningson, Anders] Umea Univ Hosp, Dept Pharmacol & Clin Neurosci, S-90185 Umea, Sweden. [Olsson, Tomas] Karolinska Inst, Ctr Mol Med, Dept Neurol, Stockholm, Sweden. RP Warnke, C (reprint author), Univ Dusseldorf, Dept Neurol, Moorenstr 5, D-40225 Dusseldorf, Germany. EM clemens.warnke@med.uni-duesseldorf.de RI Waterboer, Tim/G-1252-2010; OI Svenningsson, Anders/0000-0003-0663-2220; Pawlita, Michael/0000-0002-4720-8306 FU Research Commission of Heinrich Heine University, Dusseldorf [HHU]; German Ministry for Education and Research (BMBF; German Competence Network MS [KKNMS], Natalizumab Pharmacovigilance Study) [01GI1002]; European Committee for Treatment and Research; European Union [115303]; European Federation of Pharmaceutical Industries and Associations companies; Walter and Ilse Rose Foundation; German Research Foundation [DFG CRC TRR128]; BMBF (KKNMS); Niedersachsen Research Network on Neuroinfectiology of the Ministry of Science and Culture of Lower Saxony FX This work was supported by a local faculty grant (Research Commission of Heinrich Heine University, Dusseldorf [HHU]; O.A.) and a grant from the German Ministry for Education and Research (BMBF; German Competence Network MS [KKNMS], Natalizumab Pharmacovigilance Study, 01GI1002; B.C.K.). C.W. was supported by a European Committee for Treatment and Research in MS fellowship stipend. The research leading to these results received support from the Innovative Medicines Initiative Joint Undertaking under grant agreement No. 115303, resources of which are composed of a financial contribution from the European Union's Seventh Framework Program (FP7/2007-2013) and European Federation of Pharmaceutical Industries and Associations companies' in-kind contribution (to H.P.H., B.C.K, C.W.). The MS Center at the Department of Neurology, HHU is supported by the Walter and Ilse Rose Foundation. R.Hoh. was supported by the German Research Foundation (DFG CRC TRR128, Z2) and BMBF (KKNMS). M.S. is supported by the Niedersachsen Research Network on Neuroinfectiology of the Ministry of Science and Culture of Lower Saxony. NR 39 TC 30 Z9 30 U1 0 U2 8 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0364-5134 EI 1531-8249 J9 ANN NEUROL JI Ann. Neurol. PD DEC PY 2014 VL 76 IS 6 BP 792 EP 801 DI 10.1002/ana.24153 PG 10 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA AU6BN UT WOS:000345687600004 PM 24729444 ER PT J AU Zhou, YF Wang, SN Yu, ZX Hoyt, RF Hunt, T Kindzelski, B Shou, D Xie, W Du, YB Liu, CY Horvath, KA AF Zhou, Yifu Wang, Suna Yu, Zuxi Hoyt, Robert F., Jr. Hunt, Timothy Kindzelski, Bogdan Shou, David Xie, Wen Du, Yubin Liu, Chengyu Horvath, Keith A. TI Induced Pluripotent Stem Cell Transplantation in the Treatment of Porcine Chronic Myocardial Ischemia SO ANNALS OF THORACIC SURGERY LA English DT Article ID CORONARY-ARTERY-DISEASE; EPIGENETIC MEMORY; SOMATIC-CELLS; TOPCARE-AMI; INFARCTION; DIFFERENTIATION; PARACRINE; REGENERATION; DELIVERY; KIDNEY AB Background. This study was designed to test the effects of induced pluripotent stem cell (iPSC) in the treatment of chronic myocardial ischemia. Methods. The reprogramming of passage 3 myocardial fibroblasts was performed by using the lentiviral vector containing 4 human factors: OCT4, SOX2, KLF4, and c-MYC. The iPSC colonies at P12-17 were allogeneically transplanted into ischemic myocardium of 10 swine by direct injection. Cohorts of 2 animals were sacrificed at 2, 4, 6, 8, and 12 weeks after injection. Results. No signs of graft versus host disease were evident at any time points. At 2 weeks, clusters of SSEA-4-positive iPSCs were detected in the injected area. At 4 to 8 weeks, these cells started to proliferate into small spheres surrounded by thin capsules. At 12 weeks the cell clusters still existed, but decreased in size and numbers. The cells inside these masses were homogeneous with no sign of differentiation into any specific lineage. Increased smooth muscle actin or vWF positive cells were found inside and around the iPSC clusters, compared with non-injected areas. By real-time polymerase chain reaction, the levels of VEGF, basic FGF, and ANRT expression were significantly higher in the iPSC-treated myocardium compared with untreated areas. These results suggest that iPSCs contributed to angiogenesis. Conclusions. Allogeneically transplanted pig iPSCs proliferated despite an ischemic environment in the first 2 months and survived for at least 3 months in immunocompetent hosts. Transplanted iPSCs were also proangiogenic and thus might have beneficial effects on the ischemic heart diseases. (C) 2014 by The Society of Thoracic Surgeons C1 [Zhou, Yifu; Wang, Suna; Yu, Zuxi; Hoyt, Robert F., Jr.; Hunt, Timothy; Kindzelski, Bogdan; Shou, David; Xie, Wen; Du, Yubin; Liu, Chengyu; Horvath, Keith A.] NHLBI, Cellular Biol Sect, Cardiothorac Surg Res Program, NIH, Bethesda, MD 20892 USA. RP Zhou, YF (reprint author), NHLBI, Cellular Biol Sect, Cardiothorac Surg Res Program, NIH, 10 Ctr Dr,MSC 1550,Bldg 10,Rm B1-D47, Bethesda, MD 20892 USA. EM zhouyifu@mail.nih.gov FU Intramural NIH HHS [Z99 HL999999] NR 27 TC 3 Z9 6 U1 0 U2 9 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0003-4975 EI 1552-6259 J9 ANN THORAC SURG JI Ann. Thorac. Surg. PD DEC PY 2014 VL 98 IS 6 BP 2130 EP 2137 DI 10.1016/j.athoracsur.2014.07.008 PG 8 WC Cardiac & Cardiovascular Systems; Respiratory System; Surgery SC Cardiovascular System & Cardiology; Respiratory System; Surgery GA AU6WX UT WOS:000345743200045 PM 25443017 ER PT J AU Kindzelski, BA Li, M Mazilu, D Hunt, T Horvath, KA AF Kindzelski, Bogdan A. Li, Ming Mazilu, Dumitru Hunt, Timothy Horvath, Keith A. TI Real-Time Magnetic Resonance-Guided Aortic Valve Replacement Using Engager Valve SO ANNALS OF THORACIC SURGERY LA English DT Article ID IMPLANTATION AB Purpose. New-generation stented bioprostheses coupled with better imaging modalities are expanding the clinical utility of transcatheter aortic valve replacement (TAVR). This study aimed at evaluating the feasibility of real-time cardiovascular magnetic resonance (rtCMR) -guided TAVR using the Medtronic Engager aortic valve system in a preclinical model. Description. The Engager delivery device was slightly modified to make it CMR-compatible. Ten Yucatan swine underwent rtCMR-guided transapical TAVR. Postplacement phase-contrast and first-pass perfusion CMR sequences were used to evaluate for aortic regurgitation and myocardial perfusion, respectively. Evaluation. Real-time CMR provided excellent visualization of cardiac anatomy during TAVR. Nine of 10 animals had proper valve placement in the aortic annulus as determined by CMR and confirmed by necropsy inspection. Postplacement phase-contrast scans confirmed no intravalvular or paravalvular leaks. Perfusion scans demonstrated sufficient coronary flow. Roentgenographs confirmed proper placement of the prostheses. Conclusions. The Engager valve can be implanted transapically under rtCMR guidance with a modified, CMR-compatible delivery device in a preclinical model. Cardiovascular magnetic resonance allowed for accurate preplacement evaluation, real-time guidance, and postplacement functional assessment. (C) 2014 by The Society of Thoracic Surgeons. C1 [Kindzelski, Bogdan A.; Li, Ming; Mazilu, Dumitru; Hunt, Timothy; Horvath, Keith A.] NHLBI, Cardiothorac Surg Res Program, NIH, Bethesda, MD 20892 USA. RP Horvath, KA (reprint author), NHLBI, Cardiothorac Surg Res Program, NIH, Bldg 10,Rm B1D47,10 Ctr Dr, Bethesda, MD 20892 USA. EM horvathka@mail.nih.gov FU National Heart, Lung, and Blood Institute, NIH; NIH Medical Research Scholars Program; NIH; DHHS FX This research was made possible by funding from the Intramural Research Program of the National Heart, Lung, and Blood Institute, NIH, DHHS, and the NIH Medical Research Scholars Program, a public-private partnership supported jointly by the NIH and generous contributions to the Foundation for the NIH from Pfizer Inc, The Doris Duke Charitable Foundation, The Alexandria Real Estate Equities, Inc and Mr. and Mrs. Joel S. Marcus, and the Howard Hughes Medical Institute, as well as other private donors. The authors would like to thank Medtronic for generously providing the Engager valves and delivery devices for the rtCMR-guided experiments. The authors had full freedom of investigation. NR 10 TC 2 Z9 2 U1 0 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0003-4975 EI 1552-6259 J9 ANN THORAC SURG JI Ann. Thorac. Surg. PD DEC PY 2014 VL 98 IS 6 BP 2194 EP 2199 DI 10.1016/j.athoracsur.2014.09.017 PG 6 WC Cardiac & Cardiovascular Systems; Respiratory System; Surgery SC Cardiovascular System & Cardiology; Respiratory System; Surgery GA AU6WX UT WOS:000345743200055 PM 25468087 ER PT J AU Hendrickx, DM Boyles, RR Kleinjans, JCS Dearry, A AF Hendrickx, Diana M. Boyles, Rebecca R. Kleinjans, Jos C. S. Dearry, Allen TI Workshop report: Identifying opportunities for global integration of toxicogenomics databases, 26-27 June 2013, Research Triangle Park, NC, USA SO ARCHIVES OF TOXICOLOGY LA English DT Article DE Databases; Data sharing; Hazard identification; Human; Omics technologies; Risk assessment ID BIOLOGICAL-SYSTEMS; TOXICITY DATA; IN-VITRO; MICROARRAY; TOXICOLOGY; PROJECT; DISCOVERY; SCIENCE; DISEASE; DESIGN AB A joint US-EU workshop on enhancing data sharing and exchange in toxicogenomics was held at the National Institute for Environmental Health Sciences. Currently, efficient reuse of data is hampered by problems related to public data availability, data quality, database interoperability (the ability to exchange information), standardization and sustainability. At the workshop, experts from universities and research institutes presented databases, studies, organizations and tools that attempt to deal with these problems. Furthermore, a case study showing that combining toxicogenomics data from multiple resources leads to more accurate predictions in risk assessment was presented. All participants agreed that there is a need for a web portal describing the diverse, heterogeneous data resources relevant for toxicogenomics research. Furthermore, there was agreement that linking more data resources would improve toxicogenomics data analysis. To outline a roadmap to enhance interoperability between data resources, the participants recommend collecting user stories from the toxicogenomics research community on barriers in data sharing and exchange currently hampering answering to certain research questions. These user stories may guide the prioritization of steps to be taken for enhancing integration of toxicogenomics databases. C1 [Hendrickx, Diana M.; Kleinjans, Jos C. S.] Maastricht Univ, Dept Toxicogen, NL-6229 ER Maastricht, Netherlands. [Boyles, Rebecca R.; Dearry, Allen] NIEHS, Dept Hlth & Human Serv, NIH, Res Triangle Pk, NC 27709 USA. RP Hendrickx, DM (reprint author), Maastricht Univ, Dept Toxicogen, Univ Singel 40, NL-6229 ER Maastricht, Netherlands. EM d.hendrickx@maastrichtuniversity.nl RI Kleinjans, Jos/E-7241-2015; OI Hendrickx, Diana/0000-0001-7225-4307; Boyles, Rebecca/0000-0003-0073-6854 FU Research Data Alliance (RDA) Europe (European Union); NIEHS; NIH, National Institute of Environmental Health Sciences FX This report is based on the "Workshop on Identifying Opportunities for Global Integration of Toxicogenomics Databases", 26-27 June 2013, hosted at the National Institute of Environmental Health Sciences (NIEHS) and sponsored by Research Data Alliance (RDA) Europe (the European Union's Seventh Framework Programme) and the NIEHS. The paper reflects a consensus view of the participants of the workshop. This work was supported in part by the NIH, National Institute of Environmental Health Sciences. The views in this article are those of the authors and do not necessarily reflect the views of the NIEHS or the European Union. The authors like to thank the other participants of the workshop: Beth Plale (Indiana University, USA), Jennifer Fostel (NIEHS, USA), Ugis Sarkans (EMBL-EBI, UK), Caroline Mattingly (North Carolina State University, USA), Aravind Subramanian (Broad Institute, USA), Florian Caiment (Maastricht University, The Netherlands), Weida Tong (FDA, USA), Stephen Edwards (EPA, USA), Scott Auerbach (NIEHS, USA) and Anne Hersey (EMBL-EBI, UK). NR 33 TC 3 Z9 3 U1 0 U2 6 PU SPRINGER HEIDELBERG PI HEIDELBERG PA TIERGARTENSTRASSE 17, D-69121 HEIDELBERG, GERMANY SN 0340-5761 EI 1432-0738 J9 ARCH TOXICOL JI Arch. Toxicol. PD DEC PY 2014 VL 88 IS 12 BP 2323 EP 2332 DI 10.1007/s00204-014-1387-3 PG 10 WC Toxicology SC Toxicology GA AU6GG UT WOS:000345701100021 PM 25326818 ER PT J AU Fleischer, SJ Giesecke, C Mei, HE Lipsky, PE Daridon, C Dorner, T AF Fleischer, Sarah J. Giesecke, Claudia Mei, Henrik E. Lipsky, Peter E. Daridon, Capucine Doerner, Thomas TI Increased Frequency of a Unique Spleen Tyrosine Kinase Bright Memory B Cell Population in Systemic Lupus Erythematosus SO ARTHRITIS & RHEUMATOLOGY LA English DT Article ID TRANSCRIPTION FACTOR BRIGHT; AUTOANTIBODY PRODUCTION; REVISED CRITERIA; DISEASE-ACTIVITY; TRANSGENIC MICE; CLASSIFICATION; PATHOGENESIS; EXPRESSION; NEPHRITIS; ARTHRITIS AB Objective. Systemic lupus erythematosus (SLE) is characterized by B cell hyperactivity and autoantibody production. As spleen tyrosine kinase (Syk) is pivotal in B cell activation, these experiments aimed to examine the extent to which Syk was abnormally expressed in SLE B cells and the nature of the B cell subset that differently expressed Syk. Methods. B cells from healthy donors and SLE patients were analyzed by flow cytometry to assess basal expression of Syk and phosphorylated Syk. B cell subsets expressing higher levels of Syk were found, and their detailed phenotype, in vitro differentiation into plasmablasts/ plasma cells, and Syk induction by cytokines were determined. Results. Syk expression was higher in CD27 memory B cells than in naive B cells from SLE patients. However, a significantly increased frequency of CD27 B cells with bright expression of Syk (Syk ) was found in SLE patients. CD27 Syk B cells showed enhanced basal expression of p-Syk and stronger Syk phosphorylation upon B cell receptor (BCR) engagement as compared to CD27 Syk B cells. CD27 Syk B cells were CD38 as well as CD19 , CD20 , and mainly CD21 , with decreased ABCB1 transporter activity. In contrast to CD27 Syk B cells, CD27 Syk B cells exhibited enhanced differentiation into CD27 IgG-secreting cells and expressed somatically mutated BCR gene rearrangements. Syk B cells were inducible in vitro by stimulation with interferon-, lipopolysaccharide, or tumor necrosis factor . Conclusion. SLE patients exhibit an increased frequency of hitherto unknown CD27 Syk memorylike B cells, indicating that intracellular Syk density could distinguish CD27 memory B cells from truly naive B cell subsets. Furthermore, the CD27 Syk subset is a candidate for a source of increased plasma cells in SLE. C1 [Fleischer, Sarah J.; Giesecke, Claudia; Mei, Henrik E.; Daridon, Capucine; Doerner, Thomas] Charite, D-13353 Berlin, Germany. [Fleischer, Sarah J.; Giesecke, Claudia; Mei, Henrik E.; Daridon, Capucine; Doerner, Thomas] German Rheumatism Res Ctr Berlin, Berlin, Germany. [Lipsky, Peter E.] NIAMSD, NIH, Bethesda, MD 20892 USA. RP Dorner, T (reprint author), Charite, Dept Med Rheumatol & Clin Immunol, Charitepl 01, D-10098 Berlin, Germany. EM thomas.doerner@charite.de FU DFG [SFB650, SFB633 A14, SPP ImmunoBone DFG Do491/8-2, Do491/7-3] FX Supported by the DFG (SFB650 project TP16, SFB633 A14, SPP ImmunoBone DFG Do491/8-2, and DFG project Do491/7-3). NR 35 TC 14 Z9 14 U1 0 U2 3 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 2326-5191 EI 2326-5205 J9 ARTHRITIS RHEUMATOL JI Arthritis Rheumatol. PD DEC PY 2014 VL 66 IS 12 BP 3424 EP 3435 DI 10.1002/art.38854 PG 12 WC Rheumatology SC Rheumatology GA AU4HK UT WOS:000345571200020 PM 25156507 ER PT J AU Galski, H Oved-Gelber, T Simanovsky, M Lazarovici, P Gottesman, MM Nagler, A AF Galski, Hanan Oved-Gelber, Tamar Simanovsky, Masha Lazarovici, Philip Gottesman, Michael M. Nagler, Arnon TI P-glycoprotein-dependent resistance of cancer cells toward the extrinsic TRAIL apoptosis signaling pathway (vol 86, pg 584, 2013) SO BIOCHEMICAL PHARMACOLOGY LA English DT Correction C1 [Galski, Hanan; Oved-Gelber, Tamar; Simanovsky, Masha; Nagler, Arnon] Chaim Sheba Med Ctr, Div Hematol, Lab Mol Immunol, IL-52621 Tel Hashomer, Israel. [Lazarovici, Philip] Hebrew Univ Jerusalem, Inst Drug Sci, Sch Pharm, IL-91905 Jerusalem, Israel. [Gottesman, Michael M.] NCI, Cell Biol Lab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. RP Galski, H (reprint author), Chaim Sheba Med Ctr, Lab Mol Immunobiol, IL-52621 Ramat Gan, Israel. EM Hanan.Galski@sheba.health.gov.il NR 1 TC 0 Z9 0 U1 1 U2 2 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0006-2952 EI 1873-2968 J9 BIOCHEM PHARMACOL JI Biochem. Pharmacol. PD DEC 1 PY 2014 VL 92 IS 3 BP 518 EP 518 DI 10.1016/j.bcp.2014.08.020 PG 1 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA AW0BM UT WOS:000345955400014 ER PT J AU Qin, J Follmann, DA AF Qin, Jing Follmann, Dean A. TI Semiparametric maximum likelihood inference by using failed contact attempts to adjust for nonignorable nonresponse SO BIOMETRIKA LA English DT Article DE Call-back in survey; Nonignorable nonresponse data; Semiparametric maximum likelihood estimation AB In marketing research, social science and epidemiological studies, call-back of nonrespondents is standard. If respondents and nonrespondents tend to give different answers, the missing data are called non-ignorable, and using them alone may produce biased results. To extend earlier work on nonresponse in the presence of call-backs, Alho (1990) proposed modelling the probability of response at each attempt through logistic regression, where outcomes of interest and covariates are explanatory variables. In this paper we propose a semiparametric maximum likelihood approach, and discuss large-sample properties and the semiparametric likelihood ratio statistic used to test whether the data are missing completely at random. Simulations are conducted to evaluate this approach and a modification of the method of Alho (1990). Data from the National Health Interview Survey are used for illustration. C1 [Qin, Jing; Follmann, Dean A.] NIAID, Biostat Res Branch, Bethesda, MD 20892 USA. RP Qin, J (reprint author), NIAID, Biostat Res Branch, 9000 Rockville Pike, Bethesda, MD 20892 USA. EM jingqin@niaid.nih.gov; DFollmann@niaid.nih.gov NR 5 TC 0 Z9 0 U1 2 U2 4 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0006-3444 EI 1464-3510 J9 BIOMETRIKA JI Biometrika PD DEC PY 2014 VL 101 IS 4 BP 985 EP 991 DI 10.1093/biomet/asu046 PG 7 WC Biology; Mathematical & Computational Biology; Statistics & Probability SC Life Sciences & Biomedicine - Other Topics; Mathematical & Computational Biology; Mathematics GA AU8DZ UT WOS:000345827900018 ER PT J AU Curtis, LM Grkovic, L Mitchell, SA Steinberg, SM Cowen, EW Datiles, MB Mays, J Bassim, C Joe, G Comis, LE Berger, A Avila, D Taylor, T Pulanic, D Cole, K Baruffaldi, J Fowler, DH Gress, RE Pavletic, SZ AF Curtis, L. M. Grkovic, L. Mitchell, S. A. Steinberg, S. M. Cowen, E. W. Datiles, M. B. Mays, J. Bassim, C. Joe, G. Comis, L. E. Berger, A. Avila, D. Taylor, T. Pulanic, D. Cole, K. Baruffaldi, J. Fowler, D. H. Gress, R. E. Pavletic, S. Z. TI NIH response criteria measures are associated with important parameters of disease severity in patients with chronic GVHD SO BONE MARROW TRANSPLANTATION LA English DT Article ID VERSUS-HOST-DISEASE; CONSENSUS DEVELOPMENT PROJECT; WORKING GROUP-REPORT; CLINICAL-TRIALS; VALIDATION; SCALES AB Lack of standardized criteria measuring therapeutic response remains an obstacle to the development of better treatments for chronic GVHD (cGVHD). This cross-sectional prospective study examined the concurrent and predictive validity of 18 clinician-reported ('Form A') and 8 patient-reported ('Form B') response measures proposed by NIH criteria. Concurrent parameters of interest were NIH global score, cGVHD activity, Lee symptom score and SF36 PCS. Patient cohort included 193 adults with moderate-to-severe cGVHD. Measures associated with the highest number of outcomes were lung function score (LFS), 2-min walk, grip strength, 4-point health-care provider (HCP) and patient global scores, 11-point clinician- and patient-reported global symptom severity scores, and Karnofsky performance score (KPS). Measures associated with survival in univariate analyses led to a Cox model containing skin erythema, LFS, KPS, eosinophil count and interval from cGVHD diagnosis to enrollment as jointly associated with survival. In conclusion, 4-point HCP and patient global scores and 11-point clinician- and patient-reported global symptom severity scores are associated with the majority of concurrent outcomes. Skin erythema is a potentially reversible sign of cGVHD that is associated with survival. These results define a subset of measures that should be prioritized for evaluation in future studies. C1 [Curtis, L. M.] NCI, Med Oncol Serv, NIH, Bethesda, MD 20892 USA. [Curtis, L. M.; Grkovic, L.; Avila, D.; Taylor, T.; Cole, K.; Baruffaldi, J.; Fowler, D. H.; Gress, R. E.; Pavletic, S. Z.] NCI, Expt Transplantat & Immunol Branch, NIH, Bethesda, MD 20892 USA. [Grkovic, L.; Pulanic, D.] Univ Zagreb, Clin Hosp Ctr Zagreb, Dept Hematol, Zagreb 41000, Croatia. [Mitchell, S. A.] NCI, Outcomes Branch, Bethesda, MD 20892 USA. [Mitchell, S. A.] NCI, Div Canc Control & Populat Sci, NIH, Bethesda, MD 20892 USA. [Steinberg, S. M.] NCI, Biostat & Data Management Sect, NIH, Rockville, MD USA. [Cowen, E. W.] NCI, Dermatol Branch, NIH, Bethesda, MD 20892 USA. [Datiles, M. B.] NEI, NIH, Bethesda, MD 20892 USA. [Mays, J.; Bassim, C.] Natl Inst Dent & Craniofacial Res, Bethesda, MD USA. [Joe, G.; Comis, L. E.] NIH, Ctr Clin, Dept Rehabil Med, Bethesda, MD 20892 USA. [Berger, A.] NIH, Ctr Clin, Pain & Palliat Care Med Dept, Bethesda, MD 20892 USA. RP Pavletic, SZ (reprint author), NCI, Ctr Canc Res, NIH, Bldg 10,Room CRC 3-3330, Bethesda, MD 20892 USA. EM pavletis@mail.nih.gov OI Datiles, Manuel III B./0000-0003-4660-1664 FU National Institutes of Health, Clinical Center, Nursing and Patient Care Services; Research Program of the National Institutes of Health (NIH), National Cancer Institute, Center for Cancer Research FX This research was also supported also by National Institutes of Health, Clinical Center, Nursing and Patient Care Services. We thank all patients and their families who participated in the natural history of cGVHD protocol. This research was supported by the Intramural Research Program of the National Institutes of Health (NIH), National Cancer Institute, Center for Cancer Research. The authors are employees of the United States Government, and, as such, this work was carried out in that capacity. The views expressed do not necessarily represent the views of the National Institutes of Health or the United States Government. NR 21 TC 6 Z9 6 U1 1 U2 4 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0268-3369 EI 1476-5365 J9 BONE MARROW TRANSPL JI Bone Marrow Transplant. PD DEC PY 2014 VL 49 IS 12 BP 1513 EP 1520 DI 10.1038/bmt.2014.188 PG 8 WC Biophysics; Oncology; Hematology; Immunology; Transplantation SC Biophysics; Oncology; Hematology; Immunology; Transplantation GA AU9IM UT WOS:000345905300011 PM 25153693 ER PT J AU Pinsky, PF Nath, PH Gierada, DS Sonavane, S Szabo, E AF Pinsky, Paul F. Nath, P. Hrudaya Gierada, David S. Sonavane, Sushil Szabo, Eva TI Short- and Long-term Lung Cancer Risk Associated with Noncalcified Nodules Observed on Low-Dose CT SO CANCER PREVENTION RESEARCH LA English DT Article ID GROUND-GLASS OPACITY; COMPUTED-TOMOGRAPHY; SCREENING CT; MORTALITY; SMOKERS; TRIAL; SCAN AB Chemoprevention is an important potential tool in reducing lung cancer incidence. Noncalcified nodules (NCN) observed on low-dose computed tomography (LDCT) have been proposed as intermediate endpoints in chemoprevention trials, but whether NCNs represent cancer precursors is unclear. We analyzed data from subjects in the LDCT arm of the National Lung Screening Trial (NLST) to examine short- and long-term lung cancer risks associated with NCNs and to elucidate whether some NCNs may be cancer precursors. NLST subjects received a baseline and two additional LDCT screens and were followed for a median of 6.5 years. We examined lung cancer incidence over three distinct periods from baseline-0-23 months (short-term), 24-59 months (medium-term), and 60-84 months (long-term)-in relation to baseline NCN characteristics. Spatially, lung cancer incidence was analyzed at the person, lung, and lobe levels relative to NCN location. A total of 26,272 subjects received the baseline LDCT screen, with 468, 413, and 190 lung cancers observed in the three periods. The presence of an NCN gave significantly elevated long-term lung cancer risk ratios (RR) of 1.8, 2.4, and 3.5 at the person, lung, and lobe levels; corresponding short-term RRs were 10.3, 16.8, and 38.0. Ground-glass attenuation was positively associated with long-term lung cancer risk but inversely associated with short-term risk; NCN size was positively associated with short-term risk but not significantly associated with long-term risk. That NCNs convey significantly elevated excess long-term of lung cancer lends evidence to the hypothesis that some NCNs may be cancer precursors. (C)2014 AACR. C1 [Pinsky, Paul F.; Szabo, Eva] NCI, Canc Prevent Div, NIH, Bethesda, MD 20892 USA. [Nath, P. Hrudaya; Sonavane, Sushil] Univ Alabama Birmingham, Birmingham, AL USA. [Gierada, David S.] Washington Univ, Sch Med, St Louis, MO USA. RP Pinsky, PF (reprint author), NCI, 9609 Med Ctr Dr, Bethesda, MD 20892 USA. EM pp4f@nih.gov FU National Cancer Institute FX This study was supported by contracts from the National Cancer Institute. NR 15 TC 8 Z9 8 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 EI 1940-6215 J9 CANCER PREV RES JI Cancer Prev. Res. PD DEC PY 2014 VL 7 IS 12 BP 1179 EP 1185 DI 10.1158/1940-6207.CAPR-13-0438 PG 7 WC Oncology SC Oncology GA AU6WP UT WOS:000345742400002 PM 24755313 ER PT J AU Mohammed, A Janakiram, NB Madka, V Ritchie, RL Brewer, M Biddick, L Patlolla, JMR Sadeghi, M Lightfoot, S Steele, VE Rao, CV AF Mohammed, Altaf Janakiram, Naveena B. Madka, Venkateshwar Ritchie, Rebekah L. Brewer, Misty Biddick, Laura Patlolla, Jagan Mohan R. Sadeghi, Michael Lightfoot, Stan Steele, Vernon E. Rao, Chinthalapally V. TI Eflornithine (DFMO) Prevents Progression of Pancreatic Cancer by Modulating Ornithine Decarboxylase Signaling SO CANCER PREVENTION RESEARCH LA English DT Article ID ENGINEERED MOUSE MODELS; ALPHA-DIFLUOROMETHYLORNITHINE; C-MYC; PROSTATE CARCINOGENESIS; POLYAMINE BIOSYNTHESIS; DUCTAL ADENOCARCINOMA; CELL-PROLIFERATION; DOUBLE-BLIND; SKIN-CANCER; CHEMOPREVENTION AB Ornithine decarboxylase (ODC) is the key rate-limiting enzyme in the polyamine synthesis pathway and it is overexpressed in a variety of cancers. We found that polyamine synthesis and modulation of ODC signaling occurs at early stages of pancreatic precursor lesions and increases as the tumor progresses in Krasactivated p48(Cre/+) -LSL-Kras(G12D/+) mice. Interest in use of the ODC inhibitor eflornithine (DFMO) as a cancer chemopreventive agent has increased in recent years since ODC was shown to be transactivated by the c-myc oncogene and to cooperate with the ras oncogene in malignant transformation of epithelial tissues. We tested the effects of DFMO on pancreatic intraepithelial neoplasias (PanIN) and their progression to pancreatic ductal adenocarcinoma (PDAC) in genetically engineered Kras mice. The Kras(G12D/+) mice fed DFMO at 0.1% and 0.2% in the diet showed a significant inhibition (P < 0.0001) of PDAC incidence compared with mice fed control diet. Pancreatic tumor weights were decreased by 31% to 43% (P < 0.03-0.001) with both doses of DFMO. DFMO at 0.1% and 0.2% caused a significant suppression (27% and 31%; P < 0.02-0.004) of PanIN 3 lesions (carcinoma in situ). DFMO-treated pancreas exhibited modulated ODC pathway components along with decreased proliferation and increased expression of p21/p27 as compared with pancreatic tissues derived from mice fed control diet. In summary, our preclinical data indicate that DFMO has potential for chemoprevention of pancreatic cancer and should be evaluated in other PDAC models and in combination with other drugs in anticipation of future clinical trials. (C)2014 AACR. C1 [Mohammed, Altaf; Janakiram, Naveena B.; Madka, Venkateshwar; Ritchie, Rebekah L.; Brewer, Misty; Biddick, Laura; Patlolla, Jagan Mohan R.; Sadeghi, Michael; Lightfoot, Stan; Rao, Chinthalapally V.] Univ Oklahoma, Hlth Sci Ctr, Ctr Canc Prevent & Drug Dev, Dept Med,Hem Onc Sect, Oklahoma City, OK 73104 USA. [Steele, Vernon E.] NCI, Canc Prevent Div, Chemoprevent Agent Dev Res Grp, Bethesda, MD 20892 USA. RP Rao, CV (reprint author), Univ Oklahoma, Hlth Sci Ctr, Ctr Canc Prevent & Drug Dev, 975 NE 10th St,BRC 2,Room 1203, Oklahoma City, OK 73104 USA. EM altaf-mohammed@ouhsc.edu; cv-rao@ouhsc.edu FU National Cancer Institute [N01-CN-53300] FX This work was supported by the National Cancer Institute N01-CN-53300 to C.V. Rao. NR 50 TC 10 Z9 11 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 EI 1940-6215 J9 CANCER PREV RES JI Cancer Prev. Res. PD DEC PY 2014 VL 7 IS 12 BP 1198 EP 1209 DI 10.1158/1940-6207.CAPR-14-0176 PG 12 WC Oncology SC Oncology GA AU6WP UT WOS:000345742400004 PM 25248858 ER PT J AU Robles, AI Yang, P Jen, J McClary, AC Calhoun, K Bowman, ED Vahakangas, K Greathouse, KL Wang, Y Olivo-Marston, S Wenzlaff, AS Deng, B Schwartz, AG Ryan, BM AF Robles, Ana I. Yang, Ping Jen, Jin McClary, Andrew C. Calhoun, Kara Bowman, Elise D. Vahakangas, Kirsi Greathouse, K. Leigh Wang, Yi Olivo-Marston, Susan Wenzlaff, Angela S. Deng, Bo Schwartz, Ann G. Ryan, Brid M. TI A DRD1 Polymorphism Predisposes to Lung Cancer among Those Exposed to Secondhand Smoke during Childhood SO CANCER PREVENTION RESEARCH LA English DT Article ID DOPAMINE D1 RECEPTOR; CD4+AND CD8+T CELLS; TOBACCO-SMOKE; GENOME-WIDE; SUSCEPTIBILITY LOCUS; PARKINSONS-DISEASE; NICOTINE DEPENDENCE; CIGARETTE-SMOKING; TUMOR-GROWTH; IN-VITRO AB Lung cancer has a familial component which suggests a genetic contribution to its etiology. Given the strong evidence linking smoking with lung cancer, we studied miRNA-related loci in genes associated with smoking behavior. CHRNA, CHRNB gene families, CYP2A6, and DRD1 (dopamine receptor D1) were mined for SNPs that fell within the seed region of miRNA binding sites and then tested for associations with risk in a three-stage validation approach. A 3'UTR (untranslated region) SNP in DRD1 was associated with a lower risk of lung cancer among individuals exposed to secondhand smoke during childhood [OR, 0.69; 95% confidence interval (CI), 0.60-0.79; P < 0.0001]. This relationship was evident in both ever (OR, 0.74; 95% CI, 0.62-0.88; P = 0.001) and never smokers (OR, 0.61; 95% CI, 0.47-0.79; P < 0.0001), European American (OR, 0.65; 95% CI, 0.53-0.80; P < 0.0001), and African American (OR, 0.73; 95% CI, 0.62-0.88; P = 0.001) populations. Although much remains undefined about the long-term risks associated with exposure to secondhand smoke and heterogeneity between individuals in regard to their susceptibility to the effects of secondhand smoke, our data show an interaction between an SNP in the 3'UTR of DRD1 and exposure to secondhand smoke during childhood. Further work is needed to explore the mechanistic underpinnings of this SNP and the nature of the interaction between DRD1 and exposure to secondhand smoke during childhood. (C)2014 AACR. C1 [Robles, Ana I.; McClary, Andrew C.; Calhoun, Kara; Bowman, Elise D.; Greathouse, K. Leigh; Ryan, Brid M.] NCI, Human Carcinogenesis Lab, Ctr Canc Res, Bethesda, MD 20892 USA. [Yang, Ping] Mayo Clin, Dept Hlth Sci Res, Rochester, MN USA. [Jen, Jin] Mayo Clin, Dept Lab Med & Pathol, Rochester, MN USA. [Jen, Jin] Mayo Clin, Div Pulm & Crit Care Med, Rochester, MN USA. [McClary, Andrew C.] Stanford Univ Hosp & Clin, Dept Pathol, Stanford, CA USA. [Vahakangas, Kirsi] Univ Eastern Finland, Sch Pharm Toxicol, Fac Hlth Sci, Kuopio, Finland. [Wang, Yi] Wenzhou Med Univ, Sch Environm Sci & Publ Hlth, Div Prevent Med, Wenzhou, Zhejiang, Peoples R China. [Wang, Yi; Deng, Bo] Mayo Clin, Div Epidemiol, Rochester, MN USA. [Olivo-Marston, Susan] Ohio State Univ, Coll Publ Hlth, Div Epidemiol, Columbus, OH 43210 USA. [Wenzlaff, Angela S.; Schwartz, Ann G.] Wayne State Univ, Sch Med, Dept Oncol, Karmanos Canc Inst, Detroit, MI USA. [Deng, Bo] Third Mil Med Univ, Inst Surg Res, Daping Hosp, Dept Thorac Surg, Chongqing, Peoples R China. RP Ryan, BM (reprint author), NCI, Ctr Canc Res, Bethesda, MD 20892 USA. EM ryanb@mail.nih.gov FU Intramural Program of the Centre for Cancer Research, National Cancer Institute; NIH [R01 CA060691, P30 CA022453, HHSN26120100028C, NIH-R01-CA80127, NIH-R01-CA84354, NIH-R01-CA115857]; American Cancer Society; Mayo Clinic Cancer Center; Center for Individualized Medicine; Mayo Clinic Foundation FX This work was supported by the Intramural Program of the Centre for Cancer Research, National Cancer Institute (to A.I. Robles and B.M. Ryan), NIH R01 CA060691 (to A.G. Schwartz), contracts HHSN26120100028C (to A.G. Schwartz), NIH P30 CA022453 (to A.G. Schwartz), NIH-R01-CA80127 (to P. Yang), NIH-R01-CA84354 (to P. Yang), and NIH-R01-CA115857 (to P. Yang). J. Jen is a recipient of the New Investigator Award from the American Cancer Society and supported by funding from Mayo Clinic Cancer Center and the Center for Individualized Medicine. P. Yang, J. Jen, and Y. Wang received support from The Mayo Clinic Foundation. NR 61 TC 6 Z9 6 U1 7 U2 16 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1940-6207 EI 1940-6215 J9 CANCER PREV RES JI Cancer Prev. Res. PD DEC PY 2014 VL 7 IS 12 BP 1210 EP 1218 DI 10.1158/1940-6207.CAPR-14-0158 PG 9 WC Oncology SC Oncology GA AU6WP UT WOS:000345742400005 PM 25281486 ER PT J AU Barry, KH Moore, LE Sampson, J Yan, LY Meyer, A Oler, AJ Chung, CC Wang, ZM Yeager, M Amundadottir, L Berndt, SI AF Barry, Kathryn Hughes Moore, Lee E. Sampson, Joshua Yan, Liying Meyer, Ann Oler, Andrew J. Chung, Charles C. Wang, Zhaoming Yeager, Meredith Amundadottir, Laufey Berndt, Sonja I. TI DNA Methylation Levels at Chromosome 8q24 in Peripheral Blood Are Associated with 8q24 Cancer Susceptibility Loci SO CANCER PREVENTION RESEARCH LA English DT Article ID GENOME-WIDE ASSOCIATION; SINGLE-NUCLEOTIDE POLYMORPHISM; LONG-RANGE INTERACTION; PROSTATE-CANCER; COLORECTAL-CANCER; BLADDER-CANCER; RISK LOCI; GENETIC-VARIANTS; OVARIAN-CANCER; NONCODING RNA AB Chromosome 8q24 has emerged as an important region for genetic susceptibility to various cancers, but little is known about the contribution of DNA methylation at 8q24. To evaluate variability in DNA methylation levels at 8q24 and the relationship with cancer susceptibility single nucleotide polymorphisms (SNPs) in this region, we quantified DNA methylation levels in peripheral blood at 145 CpG sites nearby 8q24 cancer susceptibility SNPs or MYC using pyrosequencing among 80 Caucasian men in the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial. For the 60 CpG sites meeting quality control, which also demonstrated temporal stability over a 5-year period, we calculated pairwise Spearman correlations for DNA methylation levels at each CpG site with 42 8q24 cancer susceptibility SNPs. To account for multiple testing, we adjusted P values into q values reflecting the false discovery rate (FDR). In contrast to the MYC CpG sites, most sites nearby the SNPs demonstrated good reproducibility, high methylation levels, and moderate-high between-individual variation. We observed 10 statistically significant (FDR<0.05) CpG site-SNP correlations. These included correlations between an intergenic CpG site at Chr8: 128393157 and the prostate cancer SNP rs16902094 (rho = -0.54; P = 9.7 x 10(-7); q = 0.002), a PRNCR1 CpG site at Chr8: 128167809 and the prostate cancer SNP rs1456315 (rho = 0.52; P = 1.4 x 10(-6); q = 0.002), and two POU5F1B CpG sites and several prostate/colorectal cancer SNPs (for Chr8: 128498051 and rs6983267, rho = 0.46; P = 2.0 x 10(-5); q = 0.01). This is the first report of correlations between blood DNA methylation levels and cancer susceptibility SNPs at 8q24, suggesting that DNA methylation at this important susceptibility locus may contribute to cancer risk. (C)2014 AACR. C1 [Barry, Kathryn Hughes; Moore, Lee E.; Berndt, Sonja I.] NCI, Occupat & Environm Epidemiol Branch, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. [Sampson, Joshua] NCI, Biostat Branch, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. [Yan, Liying; Meyer, Ann] EpigenDx Inc, Hopkinton, MA USA. [Oler, Andrew J.] NIAID, Bioinformat & Computat Biosci Branch, Off Cyber Infrastruct & Computat Biol, Bethesda, MD 20892 USA. [Chung, Charles C.; Wang, Zhaoming; Yeager, Meredith] NCI, Canc Genom Res Lab, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. [Amundadottir, Laufey] NCI, Lab Translat Genom, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. RP Barry, KH (reprint author), NCI, Occupat & Environm Epidemiol Branch, Div Canc Epidemiol & Genet, NIH, 9609 Med Ctr Dr,Room 6E618 MSC 9771, Bethesda, MD 20892 USA. EM barrykh@mail.nih.gov RI Amundadottir, Laufey/L-7656-2016 OI Amundadottir, Laufey/0000-0003-1859-8971 FU Intramural Research Program of the National Cancer Institute; National Institute of Allergy and Infectious Diseases, NIH FX This research was supported by the Intramural Research Program of the National Cancer Institute and in part by the National Institute of Allergy and Infectious Diseases, NIH (to A. Oler). NR 49 TC 3 Z9 4 U1 0 U2 3 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1940-6207 EI 1940-6215 J9 CANCER PREV RES JI Cancer Prev. Res. PD DEC PY 2014 VL 7 IS 12 BP 1282 EP 1292 DI 10.1158/1940-6207.CAPR-14-0132 PG 11 WC Oncology SC Oncology GA AU6WP UT WOS:000345742400012 PM 25315430 ER PT J AU Brenerman, BM Illuzzi, JL Wilson, DM AF Brenerman, Boris M. Illuzzi, Jennifer L. Wilson, David M., III TI Base excision repair capacity in informing healthspan SO CARCINOGENESIS LA English DT Review ID DNA-POLYMERASE-BETA; PERFORMANCE LIQUID-CHROMATOGRAPHY; SINGLE-STRAND BREAKS; ABASIC SITES; APURINIC/APYRIMIDINIC-ENDONUCLEASE; COLON CARCINOGENESIS; HETEROZYGOUS MICE; OXIDATIVE STRESS; MOUSE MODELS; LUNG-CANCER AB Base excision repair (BER) is a frontline defense mechanism for dealing with many common forms of endogenous DNA damage, several of which can drive mutagenic or cell death outcomes. The pathway engages proteins such as glycosylases, abasic endonucleases, polymerases and ligases to remove substrate modifications from DNA and restore the genome back to its original state. Inherited mutations in genes related to BER can give rise to disorders involving cancer, immunodeficiency and neurodegeneration. Studies employing genetically defined heterozygous (haploinsufficient) mouse models indicate that partial reduction in BER capacity can increase vulnerability to both spontaneous and exposure-dependent pathologies. In humans, measurement of BER variation has been imperfect to this point, yet tools to assess BER in epidemiological surveys are steadily evolving. We provide herein an overview of the BER pathway and discuss the current efforts toward defining the relationship of BER defects with disease susceptibility. C1 [Brenerman, Boris M.; Illuzzi, Jennifer L.; Wilson, David M., III] NIA, Lab Mol Gerontol, Intramural Res Program, Natl Inst Hlth, Baltimore, MD 21224 USA. RP Wilson, DM (reprint author), NIA, Lab Mol Gerontol, Intramural Res Program, Natl Inst Hlth, Baltimore, MD 21224 USA. EM wilsonda@mail.nih.gov FU National Institutes of Health, National Institute on Aging [Z01 AG000750] FX Intramural Research Program at the National Institutes of Health, National Institute on Aging (Z01 AG000750). NR 111 TC 8 Z9 8 U1 0 U2 12 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0143-3334 EI 1460-2180 J9 CARCINOGENESIS JI Carcinogenesis PD DEC PY 2014 VL 35 IS 12 BP 2643 EP 2652 DI 10.1093/carcin/bgu225 PG 10 WC Oncology SC Oncology GA AU8HC UT WOS:000345836200002 PM 25355293 ER PT J AU Hoskins, JW Jia, JP Flandez, M Parikh, H Xiao, WM Collins, I Emmanuel, MA Ibrahim, A Powell, J Zhang, L Malats, N Bamlet, WR Petersen, GM Real, FX Amundadottir, LT AF Hoskins, Jason W. Jia, Jinping Flandez, Marta Parikh, Hemang Xiao, Wenming Collins, Irene Emmanuel, Mickey A. Ibrahim, Abdisamad Powell, John Zhang, Lizhi Malats, Nuria Bamlet, William R. Petersen, Gloria M. Real, Francisco X. Amundadottir, Laufey T. TI Transcriptome analysis of pancreatic cancer reveals a tumor suppressor function for HNF1A SO CARCINOGENESIS LA English DT Article ID GENOME-WIDE ASSOCIATION; COHORT-CONSORTIUM; GENE-EXPRESSION; POOLED-ANALYSIS; INTRAEPITHELIAL NEOPLASIA; DUCTAL ADENOCARCINOMA; CIGARETTE-SMOKING; NUCLEAR FACTOR; SUSCEPTIBILITY; CELLS AB Pancreatic ductal adenocarcinoma (PDAC) is driven by the accumulation of somatic mutations, epigenetic modifications and changes in the micro-environment. New approaches to investigating disruptions of gene expression networks promise to uncover key regulators and pathways in carcinogenesis. We performed messenger RNA-sequencing in pancreatic normal (n = 10) and tumor (n = 8) derived tissue samples, as well as in pancreatic cancer cell lines (n = 9), to determine differential gene expression (DE) patterns. Sub-network enrichment analyses identified HNF1A as the regulator of the most significantly and consistently dysregulated expression sub-network in pancreatic tumor tissues and cells (median P = 7.56 x 10(-7), median rank = 1, range = 1-25). To explore the effects of HNF1A expression in pancreatic tumor-derived cells, we generated stable HNF1A-inducible clones in two pancreatic cancer cell lines (PANC-1 and MIA PaCa-2) and observed growth inhibition (5.3-fold, P = 4.5 x 10(-5) for MIA PaCa-2 clones; 7.2-fold, P = 2.2 x 10(-5) for PANC-1 clones), and a G(0)/G(1) cell cycle arrest and apoptosis upon induction. These effects correlated with HNF1A-induced down-regulation of 51 of 84 cell cycle genes (e. g. E2F1, CDK2, CDK4, MCM2/3/4/5, SKP2 and CCND1), decreased expression of anti-apoptotic genes (e. g. BIRC2/5/6 and AKT) and increased expression of pro-apoptotic genes (e. g. CASP4/9/10 and APAF1). In light of the established role of HNF1A in the regulation of pancreatic development and homeostasis, our data suggest that it also functions as an important tumor suppressor in the pancreas. C1 [Hoskins, Jason W.; Jia, Jinping; Parikh, Hemang; Collins, Irene; Emmanuel, Mickey A.; Ibrahim, Abdisamad; Amundadottir, Laufey T.] NIH, Lab Translat Gen, Div Canc Epidemiol & Genet, Natl Canc Inst, Bethesda, MD 20892 USA. [Flandez, Marta; Malats, Nuria; Real, Francisco X.] CNIO Spanish Natl Canc Res Ctr, Epithelial Carcinogenesis Grp, E-28029 Madrid, Spain. [Xiao, Wenming] NIH, Lymphoid Malignancies Branch, Ctr Canc Res, Natl Canc Inst, Bethesda, MD 20892 USA. [Powell, John] NIH, Bioinformat & Mol Anal Sect, Div Computat Biosci, Ctr Informat Technol, Bethesda, MD 20892 USA. [Zhang, Lizhi] Dept Lab Med & Pathol, Rochester, MN 55905 USA. [Bamlet, William R.; Petersen, Gloria M.] Dept Hlth Sci Res, Div Epidemiol, Mayo Clin, Rochester, MN 55905 USA. [Real, Francisco X.] Univ Pompeu Fabra, Dept Ciencies Expt Salut, Barcelona 08003, Spain. RP Amundadottir, LT (reprint author), NIH, Lab Translat Gen, Div Canc Epidemiol & Genet, Natl Canc Inst, Bldg 10, Bethesda, MD 20892 USA. EM amundadottirl@mail.nih.gov RI Malats, Nuria/H-7041-2015; Real Arribas, Francisco/H-5275-2015; Amundadottir, Laufey/L-7656-2016; OI Malats, Nuria/0000-0003-2538-3784; Real Arribas, Francisco/0000-0001-9501-498X; Amundadottir, Laufey/0000-0003-1859-8971; Hoskins, Jason/0000-0001-6944-1996 FU Intramural Research Program of the Division of Cancer Epidemiology and Genetics; National Cancer Institute; National Institutes of Health [HHSN261200800001E] FX Intramural Research Program of the Division of Cancer Epidemiology and Genetics; National Cancer Institute; National Institutes of Health (HHSN261200800001E). NR 50 TC 9 Z9 9 U1 1 U2 8 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0143-3334 EI 1460-2180 J9 CARCINOGENESIS JI Carcinogenesis PD DEC PY 2014 VL 35 IS 12 BP 2670 EP 2678 DI 10.1093/carcin/bgu193 PG 9 WC Oncology SC Oncology GA AU8HC UT WOS:000345836200005 PM 25233928 ER PT J AU Li, WQ Pfeiffer, RM Hyland, PL Shi, JX Gu, FY Wang, ZM Bhattacharjee, S Luo, J Xiong, XQ Yeager, M Deng, X Hu, N Taylor, PR Albanes, D Caporaso, NE Gapstur, SM Amundadottir, L Chanock, SJ Chatterjee, N Landi, MT Tucker, MA Goldstein, AM Yang, XHR AF Li, Wen-Qing y Pfeiffer, Ruth M. Hyland, Paula L. Shi, Jianxin Gu, Fangyi Wang, Zhaoming Bhattacharjee, Samsiddhi Luo, Jun Xiong, Xiaoqin Yeager, Meredith Deng, Xiang Hu, Nan Taylor, Philip R. Albanes, Demetrius Caporaso, Neil E. Gapstur, Susan M. Amundadottir, Laufey Chanock, Stephen J. Chatterjee, Nilanjan Landi, Maria Teresa Tucker, Margaret A. Goldstein, Alisa M. Yang, Xiaohong R. TI Genetic polymorphisms in the 9p21 region associated with risk of multiple cancers SO CARCINOGENESIS LA English DT Article ID GENOME-WIDE ASSOCIATION; SQUAMOUS-CELL CARCINOMA; SUSCEPTIBILITY LOCI; PANCREATIC-CANCER; BREAST-CANCER; GASTRIC ADENOCARCINOMA; CHINESE POPULATION; CDKN2A MUTATIONS; IDENTIFIES 5; VARIANTS AB The chromosome 9p21 region has been implicated in the pathogenesis of multiple cancers. We analyzed 9p21 single nucleotide polymorphisms (SNPs) from eight genome-wide association studies (GWAS) with data deposited in dbGaP, including studies of esophageal squamous cell carcinoma (ESCC), gastric cancer (GC), pancreatic cancer, renal cell carcinoma (RCC), lung cancer (LC), breast cancer (BrC), bladder cancer (BC) and prostate cancer (PrC). The number of subjects ranged from 2252 (PrC) to 7619 (LC). SNP-level analyses for each cancer were conducted by logistic regression or random-effects meta-analysis. A subset-based statistical approach (ASSET) was performed to combine SNP-level P values across multiple cancers. We calculated gene-level P values using the adaptive rank truncated product method. We identified that rs1063192 and rs2157719 in the CDKN2A/2B region were significantly associated with ESCC and rs2764736 (3' of TUSC1) was associated with BC (P = 2.59 x 10(-6)). ASSET analyses identified four SNPs significantly associated with multiple cancers: rs3731239 (CDKN2A intronic) with ESCC, GC and BC (P = 3.96 x 10(-4)); rs10811474 (3' of IFNW1) with RCC and BrC (P = 0.001); rs12683422 (LINGO2 intronic) with RCC and BC (P = 5.93 x 10(-4)) and rs10511729 (3' of ELAVL2) with LC and BrC (P = 8.63 x 10(-4)). At gene level, CDKN2B, CDKN2A and CDKN2B-AS1 were significantly associated with ESCC (P = 4.70 x 10(-5)). Rs10511729 and rs10811474 were associated with cis-expression of 9p21 genes in corresponding cancer tissues in the expression quantitative trait loci analysis. In conclusion, we identified several genetic variants in the 9p21 region associated with the risk of multiple cancers, suggesting that this region may contribute to a shared susceptibility across different cancer types. C1 [Li, Wen-Qing y; Pfeiffer, Ruth M.; Hyland, Paula L.; Shi, Jianxin; Gu, Fangyi; Wang, Zhaoming; Yeager, Meredith; Deng, Xiang; Hu, Nan; Taylor, Philip R.; Albanes, Demetrius; Caporaso, Neil E.; Amundadottir, Laufey; Chanock, Stephen J.; Chatterjee, Nilanjan; Landi, Maria Teresa; Tucker, Margaret A.; Goldstein, Alisa M.; Yang, Xiaohong R.] NIH, Div Canc Epidemiol & Genet, NCI, Bethesda, MD 20892 USA. [Li, Wen-Qing y] Brown Univ, Dept Dermatol, Warren Alpert Med Sch, Providence, RI 02912 USA. [Wang, Zhaoming; Yeager, Meredith; Deng, Xiang] SAIC Frederick Inc, NCI Frederick, Can Genom Res Lab, Frederick, MD USA. [Bhattacharjee, Samsiddhi] Nat Inst Biomed Gen, Kalyani, W Bengal, India. [Xiong, Xiaoqin] Informat Management Serv Inc, Calverton, MD USA. [Gapstur, Susan M.] Amer Canc Soc, Epidemiol Res Program, Atlanta, GA 30329 USA. RP Li, WQ (reprint author), NIH, Div Canc Epidemiol & Genet, NCI, Bldg 10, Bethesda, MD 20892 USA. EM wen-qing_li@brown.edu; royang@mail.nih.gov RI Tucker, Margaret/B-4297-2015; Albanes, Demetrius/B-9749-2015; Amundadottir, Laufey/L-7656-2016 OI Amundadottir, Laufey/0000-0003-1859-8971 FU Intramural Research Program of the National Institute of Health (NIH); National Cancer Institute; Division of Cancer Epidemiology and Genetics FX Intramural Research Program of the National Institute of Health (NIH); National Cancer Institute; Division of Cancer Epidemiology and Genetics. NR 44 TC 19 Z9 19 U1 1 U2 15 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0143-3334 EI 1460-2180 J9 CARCINOGENESIS JI Carcinogenesis PD DEC PY 2014 VL 35 IS 12 BP 2698 EP 2705 DI 10.1093/carcin/bgu203 PG 8 WC Oncology SC Oncology GA AU8HC UT WOS:000345836200008 PM 25239644 ER PT J AU Saud, SM Li, WD Morris, NL Matter, MS Colburn, NH Kim, YS Young, MR AF Saud, Shakir M. Li, Weidong Morris, Nicole L. Matter, Matthias S. Colburn, Nancy H. Kim, Young S. Young, Matthew R. TI Resveratrol prevents tumorigenesis in mouse model of Kras activated sporadic colorectal cancer by suppressing oncogenic Kras expression SO CARCINOGENESIS LA English DT Article ID FAMILIAL ADENOMATOUS POLYPOSIS; K-RAS; TUMOR-SUPPRESSOR; COLON; CELLS; GENE; PROGRESSION; MUTATIONS; CARCINOMA; APC AB Sporadic and non-hereditary mutations account for the majority of colorectal cancers (CRC). After the loss of adenomatous polyposis coli (APC) function and activation of the beta-catenin/LEF signaling pathway, activating mutations in Kras are major drivers of sporadic CRC. Preventing the outgrowth of cells that develop sporadic mutations will decrease CRC. Resveratrol, a naturally occurring polyphenolic compound has anti-inflammatory, anti-oxidant and anti-cancer activities. We used a genetically engineered mouse model for sporadic CRC where the APC locus is knocked out and Kras is activated specifically in the distal colon to determine the effects of resveratrol on preventing and treating CRC. Feeding mice a diet supplemented with 150 or 300 ppm resveratrol (105 and 210 mg daily human equivalent dose, respectively) before tumors were visible by colonoscopy resulted in a 60% inhibition of tumor production. In the 40% of mice that did develop tumors Kras expression was lost in the tumors. In a therapeutic assay where tumors were allowed to develop prior to treatment, feeding tumor bearing mice with resveratrol resulted in a complete remission in 33% of the mice and a 97% decrease in tumor size in the remaining mice. Analysis of miRNA expression in non-tumoral and tumoral colonic tissue of resveratrol treated mice showed an increased expression of miR-96, a miRNA previously shown to regulate Kras translation. These data indicate that resveratrol can prevent the formation and growth of colorectal tumors by downregulating Kras expression. C1 [Saud, Shakir M.; Kim, Young S.] NCI, Nutr Sci Res Grp, Canc Prevent Div, Rockville, MD USA. [Saud, Shakir M.; Li, Weidong; Young, Matthew R.] NCI, Lab Canc Prevent, Ctr Canc Res, Frederick, MD 21701 USA. [Li, Weidong] China Acad Chinese Med Sci, Dept Oncol, Guanganmen Hosp, Beijing, Peoples R China. [Morris, Nicole L.] Leidos Biomed Res Inc, Lab Anim Sci Program, Frederick, MD USA. [Matter, Matthias S.] NCI, Expt Carcinogenesis Lab, Ctr Canc Res, Bethesda, MD 20892 USA. RP Young, MR (reprint author), NCI, 1050 Boyles St, Ft Detrick, MD 21702 USA. EM youngma@mail.nih.gov FU Office of Dietary Supplements, Office of the Director; Division of Cancer Prevention; Intramural Research Program, National Cancer Institute; Department of Health and Human Services (DHHS), National Institutes of Health, Bethesda, MD [ZIA BC 010025] FX The Office of Dietary Supplements, Office of the Director; the Division of Cancer Prevention and the Intramural Research Program, National Cancer Institute; Department of Health and Human Services (DHHS), National Institutes of Health, Bethesda, MD (ZIA BC 010025). NR 41 TC 14 Z9 16 U1 0 U2 9 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0143-3334 EI 1460-2180 J9 CARCINOGENESIS JI Carcinogenesis PD DEC PY 2014 VL 35 IS 12 BP 2778 EP 2786 DI 10.1093/carcin/bgu209 PG 9 WC Oncology SC Oncology GA AU8HC UT WOS:000345836200018 PM 25280562 ER PT J AU Benabentos, R Ray, P Kumar, D AF Benabentos, Rocio Ray, Payal Kumar, Deepak TI Addressing Health Disparities in the Undergraduate Curriculum: An Approach to Develop a Knowledgeable Biomedical Workforce SO CBE-LIFE SCIENCES EDUCATION LA English DT Article ID MEDICAL-EDUCATION; CARE DISPARITIES; IMPROVE CARE; PHYSICIANS AB Disparities in health and healthcare are a major concern in the United States and worldwide. Approaches to alleviate these disparities must be multifaceted and should include initiatives that touch upon the diverse areas that influence the healthcare system. Developing a strong biomedical workforce with an awareness of the issues concerning health disparities is crucial for addressing this issue. Establishing undergraduate health disparities courses that are accessible to undergraduate students in the life sciences is necessary to increase students' understanding and awareness of these issues and motivate them to address these disparities during their careers. The majority of universities do not include courses related to health disparities in their curricula, and only a few universities manage them from their life sciences departments. The figures are especially low for minority-serving institutions, which serve students from communities disproportionally affected by health disparities. Universities should consider several possible approaches to infuse their undergraduate curricula with health disparities courses or activities. Eliminating health disparities will require efforts from diverse stakeholders. Undergraduate institutions can play an important role in developing an aware biomedical workforce and helping to close the gap in health outcomes. C1 [Benabentos, Rocio] Natl Sci Fdn, Div Human Resource Dev, Directorate Educ & Human Resources, Arlington, VA 22230 USA. [Ray, Payal] NICHHD, NIH, Bethesda, MD 20892 USA. [Benabentos, Rocio; Ray, Payal; Kumar, Deepak] Univ Dist Columbia, Coll Arts & Sci, Dept Biol Chem & Phys, Washington, DC 20008 USA. RP Kumar, D (reprint author), Univ Dist Columbia, Coll Arts & Sci, Dept Biol Chem & Phys, Washington, DC 20008 USA. EM dkumar@udc.edu FU CDMPRP Prostate Cancer Research Program [PC073564, PC131862, PC111314]; National Cancer Institute Center to Reduce Cancer Health Disparities [CA162264] FX The authors thank Shifali Arora, Oni Celestin, Sharmi Das, Patricia Forcinito, Natasha Lugo-Escobar, Steve Schultz, and Susan Singer for insightful comments and suggestions. R.B. thanks Beth Mitchneck and Sylvia James for support of this work. Any opinions, findings, and conclusions or recommendations expressed in this material are those of the authors alone and do not necessarily reflect the views of the National Science Foundation, NIH, AAAS, or any other organizations with which the authors are affiliated. D.K. gratefully acknowledges the support from the CDMPRP Prostate Cancer Research Program (PC073564, PC131862, PC111314) and the National Cancer Institute Center to Reduce Cancer Health Disparities (CA162264). NR 29 TC 0 Z9 0 U1 2 U2 4 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1931-7913 J9 CBE-LIFE SCI EDUC JI CBE-Life Sci. Educ. PD DEC 1 PY 2014 VL 13 IS 4 BP 636 EP 640 DI 10.1187/cbe.14-06-0101 PG 5 WC Education, Scientific Disciplines SC Education & Educational Research GA AU7FR UT WOS:000345766800010 PM 25452486 ER PT J AU Akinkugbe, A Iafolla, T Chattopadhyay, A Garcia, I Adams, A Kingman, A AF Akinkugbe, Aderonke Iafolla, Timothy Chattopadhyay, Amit Garcia, Isabel Adams, Amy Kingman, Albert TI The role of partial recording protocols in reporting prevalence and severity of dental fluorosis SO COMMUNITY DENTISTRY AND ORAL EPIDEMIOLOGY LA English DT Article DE bias; correction factor; dental fluorosis; fluorosis; negative predictive value; partial recording protocols; sensitivity; subset of teeth ID PERIODONTAL-DISEASE; DRINKING-WATER; FLUORIDE; INDEX; COMMUNITIES; PATTERNS AB ObjectivesTo evaluate the role of partial recording protocols (PRPs) in reporting prevalence and severity of dental fluorosis and assess whether prevalence/severity estimates derived from PRPs differ by race/ethnicity. MethodsData from the National Health and Nutrition Examination Survey (NHANES) for the years 1999-2004 were analyzed with Stata((R)) v.11. Prevalence of dental fluorosis obtained from a full-mouth examination (28 teeth gold standard) was compared with estimates derived from four subsets of teeth (maxillary canine-to-canine; maxillary first-premolar-to-first-premolar; all-premolars; all-molars). Sensitivity, negative predictive value (NPV), absolute bias, and correction factors were calculated against gold standard estimate. Analysis was stratified according to race/ethnicity to assess differences in estimates derived from PRPs. ResultsAll subsets underestimated prevalence albeit to varying degrees. Two subsets (all-premolars and all-molars) had prevalence and severity estimates closest to gold standard estimates. The all-molars subset (eight teeth) recorded the highest sensitivity (84.5%) and the lowest absolute bias (3.5%) of all subsets relative to gold standard. Subsets derived from esthetically relevant teeth produced the lowest fluorosis prevalence. For instance, the maxillary canine-to-canine subset underestimated prevalence by 9.5%; incorporating the maxillary first premolars in the span improved prevalence estimate by 31%. Among non-Hispanic Whites, the all-premolars subset produced estimates closest to gold standard while the all-molars subset produced estimates closest to the gold standard among non-Hispanic Blacks and Hispanics. ConclusionWhile the majority of dental fluorosis in the United States is very mild, concerns regarding its growing prevalence underscore the need for careful monitoring. The use of PRPs offers an alternative method of assessment, with validity of reported prevalence and severity dependent on choice of subset. C1 [Akinkugbe, Aderonke] Univ N Carolina, Dept Epidemiol, Chapel Hill, NC USA. [Iafolla, Timothy; Chattopadhyay, Amit; Adams, Amy; Kingman, Albert] NIDCR, Off Sci Policy & Anal, NIH, Bethesda, MD 20892 USA. [Garcia, Isabel] NIDCR, NIH, Bethesda, MD 20892 USA. RP Chattopadhyay, A (reprint author), NIDCR, NIH, 31 Ctr Dr,5B55 MSC 2190, Bethesda, MD 20892 USA. EM Amit.Chattopadhyay@nih.gov FU NIDCR's Dental Public Health Residency Program; NIH/NIDCR Training Grant [R90 DE022527] FX The authors gratefully acknowledge Drs. Eugenio Beltran-Aguilar and Bruce Dye for providing very useful historical perspectives about the NHANES and the dental examination portion of the NHANES. This work was supported by NIDCR's Dental Public Health Residency Program. Dr. Akinkugbe's work was partly supported by the NIH/NIDCR Training Grant R90 DE022527. NR 27 TC 0 Z9 0 U1 2 U2 5 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0301-5661 EI 1600-0528 J9 COMMUNITY DENT ORAL JI Community Dentist. Oral Epidemiol. PD DEC PY 2014 VL 42 IS 6 BP 563 EP 571 DI 10.1111/cdoe.12115 PG 9 WC Dentistry, Oral Surgery & Medicine; Public, Environmental & Occupational Health SC Dentistry, Oral Surgery & Medicine; Public, Environmental & Occupational Health GA AU6EE UT WOS:000345695000009 PM 24995860 ER PT J AU Scott, BH Mishkin, M Yin, PB AF Scott, Brian H. Mishkin, Mortimer Yin, Pingbo TI Neural Correlates of Auditory Short-Term Memory in Rostral Superior Temporal Cortex SO CURRENT BIOLOGY LA English DT Article ID SINGLE-UNIT-ACTIVITY; PREFRONTAL CORTEX; RECOGNITION MEMORY; WORKING-MEMORY; BEHAVIORAL DEPENDENCY; RHESUS-MONKEYS; VISUAL MEMORY; TASK; INFORMATION; PITCH AB Background: Auditory short-term memory (STM) in the monkey is less robust than visual STM and may depend on a retained sensory trace, which is likely to reside in the higher-order cortical areas of the auditory ventral stream. Results: We recorded from the rostral superior temporal cortex as monkeys performed serial auditory delayed match-to-sample (DMS). A subset of neurons exhibited modulations of their firing rate during the delay between sounds, during the sensory response, or during both. This distributed subpopulation carried a predominantly sensory signal modulated by the mnemonic context of the stimulus. Excitatory and suppressive effects on match responses were dissociable in their timing and in their resistance to sounds intervening between the sample and match. Conclusions: Like the monkeys' behavioral performance, these neuronal effects differ from those reported in the same species during visual DMS, suggesting different neural mechanisms for retaining dynamic sounds and static images in STM. C1 [Scott, Brian H.; Mishkin, Mortimer; Yin, Pingbo] NIMH, Neuropsychol Lab, NIH, Bethesda, MD 20892 USA. [Yin, Pingbo] Univ Maryland, Syst Res Inst, Neural Syst Lab, College Pk, MD 20742 USA. RP Scott, BH (reprint author), NIMH, Neuropsychol Lab, NIH, Bldg 9, Bethesda, MD 20892 USA. EM brianscott@mail.nih.gov FU Intramural Research Program of the NIMH/NIH/DHHS FX We thank H. Tak, M. Munoz-Lopez, K. Moorhead, P. Sergo, A. Kloth, and H. Vinal for assistance with animal training and data collection and R.C. Saunders and M. Malloy for providing technical expertise. This research was supported by the Intramural Research Program of the NIMH/NIH/DHHS. NR 48 TC 6 Z9 6 U1 0 U2 4 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 0960-9822 EI 1879-0445 J9 CURR BIOL JI Curr. Biol. PD DEC 1 PY 2014 VL 24 IS 23 BP 2767 EP 2775 DI 10.1016/j.cub.2014.10.004 PG 9 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA AU7WH UT WOS:000345808700017 PM 25456448 ER PT J AU Feldblum, JT Wroblewski, EE Rudicell, RS Hahn, BH Paiva, T Cetinkaya-Rundel, M Pusey, AE Gilby, IC AF Feldblum, Joseph T. Wroblewski, Emily E. Rudicell, Rebecca S. Hahn, Beatrice H. Paiva, Thais Cetinkaya-Rundel, Mine Pusey, Anne E. Gilby, Ian C. TI Sexually Coercive Male Chimpanzees Sire More Offspring SO CURRENT BIOLOGY LA English DT Article ID PAN-TROGLODYTES-SCHWEINFURTHII; KIBALE NATIONAL-PARK; FEMALE CHOICE; WILD CHIMPANZEES; GENETIC-MARKERS; COTE-DIVOIRE; AGGRESSION; DOMINANCE; VERUS; PRIMATES AB In sexually reproducing animals, male and female reproductive strategies often conflict [1]. In some species, males use aggression to overcome female choice [2, 3], but debate persists over the extent to which this strategy is successful. Previous studies of male aggression toward females among wild chimpanzees have yielded contradictory results about the relationship between aggression and mating behavior [4-11]. Critically, however, copulation frequency in primates is not always predictive of reproductive success [12]. We analyzed a 17-year sample of behavioral and genetic data from the Kasekela chimpanzee (Pan troglodytes schweinfurthii)community in Gombe National Park, Tanzania, to test the hypothesis that male aggression toward females increases male reproductive success. We examined the effect of male aggression toward females during ovarian cycling, including periods when the females were sexually receptive (swollen) and periods when they were not. We found that, after controlling for confounding factors, male aggression during a female's swollen periods was positively correlated with copulation frequency. However, aggression toward swollen females was not predictive of paternity. Instead, aggression by high-ranking males toward females during their nonswollen periods was positively associated with likelihood of paternity. This indicates that long-term patterns of intimidation allow high-ranking males to increase their reproductive success, supporting the sexual coercion hypothesis. To our knowledge, this is the first study to present genetic evidence of sexual coercion as an adaptive strategy in a social mammal. C1 [Feldblum, Joseph T.; Pusey, Anne E.] Duke Univ, Dept Evolutionary Anthropol, Durham, NC 27708 USA. [Wroblewski, Emily E.] Stanford Univ, Sch Med, Dept Biol Struct, Stanford, CA 94305 USA. [Rudicell, Rebecca S.] NIH, Vaccine Res Ctr, Bethesda, MD 20892 USA. [Rudicell, Rebecca S.] Sanofi, Cambridge, MA 02139 USA. [Hahn, Beatrice H.] Univ Penn, Perelman Sch Med, Dept Med, Philadelphia, PA 19104 USA. [Hahn, Beatrice H.] Univ Penn, Perelman Sch Med, Dept Microbiol, Philadelphia, PA 19104 USA. [Paiva, Thais; Cetinkaya-Rundel, Mine] Duke Univ, Dept Stat Sci, Durham, NC 27708 USA. [Gilby, Ian C.] Arizona State Univ, Sch Human Evolut & Social Change, Tempe, AZ 85287 USA. RP Feldblum, JT (reprint author), Duke Univ, Dept Evolutionary Anthropol, Durham, NC 27708 USA. EM jtf9@duke.edu FU National Science Foundation (NSF) [LTREB-1052693]; National Institutes of Health (NIH) [R01 AI 058715]; NSF [LTREB-1052693, DBS-9021946, SBR-9319909, BCS-0452315, BCS-0648481]; NIH [R01 AI 058715]; University of Minnesota; Harris Steel Group; Windibrow Foundation; JGI; Carnegie Corporation; Duke University FX Data collection was supported primarily by the Jane Goodall Institute (JGI), with additional support from the National Science Foundation (NSF) (LTREB-1052693) and the National Institutes of Health (NIH) (R01 AI 058715). Digitization and analysis of behavioral and genetic data were supported by grants from the NSF (DBS-9021946, SBR-9319909, BCS-0452315, BCS-0648481, and LTREB-1052693), the NIH (R01 AI 058715), the University of Minnesota, the Harris Steel Group, the Windibrow Foundation, JGI, the Carnegie Corporation, and Duke University. We thank Jane Goodall for permission to work with the long-term data and the Tanzania National Parks, Tanzania Wildlife Research Institute, and Tanzania Commission for Science and Technology for permission to work in Gombe National Park. All data collection was approved by these Tanzanian bodies and the Duke University Institutional Animal Care and Use Committee. We are very grateful to the wonderful Gombe Stream Research Center staff for their heroic data collection; Esther Collins for translation; Joann Schumacher-Stankey for data extraction; and Kara Schroepfer-Walker, Emily Boehm, Steffen Foerster, Susan Alberts, Mathias Franz, Amanda Lea, Sammy Feldblum, and Amelia O'Rourke-Owens for thoughtful comments and invaluable technical advice. NR 40 TC 16 Z9 16 U1 15 U2 65 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 0960-9822 EI 1879-0445 J9 CURR BIOL JI Curr. Biol. PD DEC 1 PY 2014 VL 24 IS 23 BP 2855 EP 2860 DI 10.1016/j.cub.2014.10.039 PG 6 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA AU7WH UT WOS:000345808700031 PM 25454788 ER PT J AU Walters, AD May, CK Dauster, ES Cinquin, BP Smith, EA Robellet, X D'Amours, D Larabell, CA Cohen-Fix, O AF Walters, Alison D. May, Christopher K. Dauster, Emma S. Cinquin, Bertrand P. Smith, Elizabeth A. Robellet, Xavier D'Amours, Damien Larabell, Carolyn A. Cohen-Fix, Orna TI The Yeast Polo Kinase Cdc5 Regulates the Shape of the Mitotic Nucleus SO CURRENT BIOLOGY LA English DT Article ID SISTER-CHROMATID SEPARATION; CHROMOSOME CONDENSATION; BUDDING-YEAST; SACCHAROMYCES-CEREVISIAE; GENOME STABILITY; IN-VIVO; ENVELOPE; EXIT; PHOSPHORYLATION; NETWORK AB Abnormal nuclear size and shape are hallmarks of aging and cancer [1, 2]. However, the mechanisms regulating nuclear morphology and nuclear envelope (NE) expansion are poorly understood. In metazoans, the NE disassembles prior to chromosome segregation and reassembles at the end of mitosis [3]. In budding yeast, the NE remains intact. The nucleus elongates as chromosomes segregate and then divides at the end of mitosis to form two daughter nuclei without NE disassembly. The budding yeast nucleus also undergoes remodeling during a mitotic arrest; the NE continues to expand despite the pause in chromosome segregation, forming a nuclear extension, or "flare," that encompasses the nucleolus [4]. The distinct nucleolar localization of the mitotic flare indicates that the NE is compartmentalized and that there is a mechanism by which NE expansion is confined to the region adjacent to the nucleolus. Here we show that mitotic flare formation is dependent on the yeast polo kinase Cdc5. This function of Cdc5 is independent of its known mitotic roles, including rDNA condensation. High-resolution imaging revealed that following Cdc5 inactivation, nuclei expand isometrically rather than forming a flare, indicating that Cdc5 is needed for NE compartmentalization. Even in an uninterrupted cell cycle, a small NE expansion occurs adjacent to the nucleolus prior to anaphase in a Cdc5-dependent manner. Our data provide the first evidence that polo kinase, a key regulator of mitosis [5], plays a role in regulating nuclear morphology and NE expansion. C1 [Walters, Alison D.; May, Christopher K.; Dauster, Emma S.; Cohen-Fix, Orna] NIDDK, Mol & Cellular Biol Lab, NIH, Bethesda, MD 20892 USA. [Cinquin, Bertrand P.; Smith, Elizabeth A.; Larabell, Carolyn A.] Univ Calif San Francisco, Dept Anat, San Francisco, CA 94158 USA. [Cinquin, Bertrand P.; Smith, Elizabeth A.; Larabell, Carolyn A.] Univ Calif Berkeley, Lawrence Berkeley Natl Lab, Phys Biosci Div, Berkeley, CA 94720 USA. [Robellet, Xavier; D'Amours, Damien] Univ Montreal, Inst Res Immunol & Canc, Montreal, PQ H3C 3J7, Canada. [Robellet, Xavier; D'Amours, Damien] Univ Montreal, Dept Pathol & Biol Cellulaire, Montreal, PQ H3C 3J7, Canada. RP Cohen-Fix, O (reprint author), NIDDK, Mol & Cellular Biol Lab, NIH, Bethesda, MD 20892 USA. EM ornac@helix.nih.gov FU National Institute of Diabetes and Digestive and Kidney Diseases; National Institute of General Medical Science of the NIH [P41GM103445]; U.S. Department of Energy, Office of Biological and Environmental Research [DE-AC02-05CH11231]; Canadian Institutes of Health Research [MOP 82912, MOP 136788]; Canada Research Chair in Cell Cycle Regulation and Genomic Integrity FX We thank D. Reynolds, A. Hoyt, T. Eng, D. Koshland, A. Amon, S. Lacefield, and J. Diffley for yeast strains and plasmids and M. Lichten, W. Prinz, F. Chang, and members of the O.C.-F. laboratory for discussions on the manuscript. A.D.W., C.K.M., E.S.D., and O.C.-F. are funded by an intramural National Institute of Diabetes and Digestive and Kidney Diseases grant. C.A.L., B.P.C., and E.A.S. are funded by the National Institute of General Medical Science of the NIH (P41GM103445) and the U.S. Department of Energy, Office of Biological and Environmental Research (DE-AC02-05CH11231). Research in D.D.'s laboratory is supported by the Canadian Institutes of Health Research (MOP 82912 and MOP 136788). D.D. is a recipient of a Tier II Canada Research Chair in Cell Cycle Regulation and Genomic Integrity. NR 31 TC 7 Z9 7 U1 2 U2 9 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 0960-9822 EI 1879-0445 J9 CURR BIOL JI Curr. Biol. PD DEC 1 PY 2014 VL 24 IS 23 BP 2861 EP 2867 DI 10.1016/j.cub.2014.10.029 PG 7 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA AU7WH UT WOS:000345808700032 PM 25454593 ER PT J AU Heffner, KM Hizal, DB Kumar, A Shiloach, J Zhu, J Bowen, MA Betenbaugh, MJ AF Heffner, Kelley M. Hizal, Deniz Baycin Kumar, Amit Shiloach, Joseph Zhu, Jie Bowen, Michael A. Betenbaugh, Michael J. TI Exploiting the proteomics revolution in biotechnology: from disease and antibody targets to optimizing bioprocess development SO CURRENT OPINION IN BIOTECHNOLOGY LA English DT Review ID HAMSTER OVARY CELLS; ESCHERICHIA-COLI; MONOCLONAL-ANTIBODIES; SHOTGUN PROTEOMICS; PROTEIN; IDENTIFICATION; CULTURE; GENOME; SERUM; CLEAVAGE AB Recent advancements in proteomics have enabled the generation of high-quality data sets useful for applications ranging from target and monoclonal antibody (mAB) discovery to bioprocess optimization. Comparative proteomics approaches have recently been used to identify novel disease targets in oncology and other disease conditions. Proteomics has also been applied as a new avenue for mAb discovery. Finally, CHO and Escherichia coli cells represent the dominant production hosts for biopharmaceutical development, yet the physiology of these cells types has yet to be fully established. Proteomics approaches can provide new insights into these cell types, aiding in recombinant protein production, cell growth regulation, and medium formulation. Optimization of sample preparations and protein database developments are enhancing the quantity and accuracy of proteomic results. In these ways, innovations in proteomics are enriching biotechnology and bioprocessing research across a wide spectrum of applications. C1 [Heffner, Kelley M.; Kumar, Amit; Betenbaugh, Michael J.] Johns Hopkins Univ, Baltimore, MD 21218 USA. [Hizal, Deniz Baycin; Zhu, Jie; Bowen, Michael A.] MedImmune LLC, Antibody Discovery & Prot Engn, Gaithersburg, MD 20878 USA. [Kumar, Amit; Shiloach, Joseph] NIDDK, NIH, Bethesda, MD 20892 USA. RP Heffner, KM (reprint author), Johns Hopkins Univ, Baltimore, MD 21218 USA. FU National Science Foundation [DGE-1232825] FX This material is based upon work supported by the National Science Foundation Graduate Research Fellowship Program under Grant No. DGE-1232825. Any opinions, findings, and conclusions or recommendations expressed in this material are those of the author(s) and do not necessarily reflect the views of the National Science Foundation. NR 44 TC 8 Z9 9 U1 2 U2 32 PU CURRENT BIOLOGY LTD PI LONDON PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND SN 0958-1669 EI 1879-0429 J9 CURR OPIN BIOTECH JI Curr. Opin. Biotechnol. PD DEC PY 2014 VL 30 BP 80 EP 86 DI 10.1016/j.copbio.2014.06.006 PG 7 WC Biochemical Research Methods; Biotechnology & Applied Microbiology SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology GA AU8BS UT WOS:000345822300014 PM 24997444 ER PT J AU Adney, DR van Doremalen, N Brown, VR Bushmaker, T Scott, D de Wit, E Bowen, RA Munster, VJ AF Adney, Danielle R. van Doremalen, Neeltje Brown, Vienna R. Bushmaker, Trenton Scott, Dana de Wit, Emmie Bowen, Richard A. Munster, Vincent J. TI Replication and Shedding of MERS-CoV in Upper Respiratory Tract of Inoculated Dromedary Camels SO EMERGING INFECTIOUS DISEASES LA English DT Article ID SYNDROME CORONAVIRUS; SAUDI-ARABIA; INFECTION; ANTIBODIES; LIVESTOCK; JUNE AB In 2012, a novel coronavirus associated with severe respiratory disease in humans emerged in the Middle East. Epidemiologic investigations identified dromedary camels as the likely source of zoonotic transmission of Middle East respiratory syndrome coronavirus (MERS-CoV). Here we provide experimental support for camels as a reservoir for MERS-CoV. We inoculated 3 adult camels with a human isolate of MERS-CoV and a transient, primarily upper respiratory tract infection developed in each of the 3 animals. Clinical signs of the MERS-CoV infection were benign, but each of the camels shed large quantities of virus from the upper respiratory tract. We detected infectious virus in nasal secretions through 7 days postinoculation, and viral RNA up to 35 days postinoculation. The pattern of shedding and propensity for the upper respiratory tract infection in dromedary camels may help explain the lack of systemic illness among naturally infected camels and the means of efficient camel-to-camel and camel-to-human transmission. C1 [Adney, Danielle R.; Brown, Vienna R.; Bowen, Richard A.] Colorado State Univ, Ft Collins, CO 80523 USA. [van Doremalen, Neeltje; Bushmaker, Trenton; Scott, Dana; de Wit, Emmie; Munster, Vincent J.] NIH, Hamilton, MT USA. RP Bowen, RA (reprint author), Colorado State Univ, Dept Biomed Sci, W113 ARBL Bldg,Foothills Campus, Ft Collins, CO 80523 USA. EM Richard.Bowen@colostate.edu OI de Wit, Emmie/0000-0002-9763-7758; Munster, Vincent/0000-0002-2288-3196 FU National Institute of Allergy and Infectious Diseases, National Institutes of Health; Animal Models Core at Colorado State University; Colorado State University FX This work was supported by the Intramural Research Program of the National Institute of Allergy and Infectious Diseases, National Institutes of Health, and the Animal Models Core at Colorado State University. D.R.A. was supported through the Infectious Disease: Translational Research Training Program at Colorado State University. NR 29 TC 70 Z9 71 U1 2 U2 19 PU CENTERS DISEASE CONTROL PI ATLANTA PA 1600 CLIFTON RD, ATLANTA, GA 30333 USA SN 1080-6040 EI 1080-6059 J9 EMERG INFECT DIS JI Emerg. Infect. Dis PD DEC PY 2014 VL 20 IS 12 BP 1999 EP 2005 DI 10.3201/eid2012.141280 PG 7 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA AU6RP UT WOS:000345729900004 PM 25418529 ER PT J AU Yondon, M Zayat, B Nelson, MI Heil, GL Anderson, BD Lin, XD Halpin, RA McKenzie, PP White, SK Wentworth, DE Gray, GC AF Yondon, Myagmarsukh Zayat, Batsukh Nelson, Martha I. Heil, Gary L. Anderson, Benjamin D. Lin, Xudong Halpin, Rebecca A. McKenzie, Pamela P. White, Sarah K. Wentworth, David E. Gray, Gregory C. TI Equine Influenza A(H3N8) Virus Isolated from Bactrian Camel, Mongolia SO EMERGING INFECTIOUS DISEASES LA English DT Article ID A VIRUS; H1N1 AB Because little is known about the ecology of influenza viruses in camels, 460 nasal swab specimens were collected from healthy (no overt illness) Bactrian camels in Mongolia during 2012. One specimen was positive for influenza A virus (A/camel/Mongolia/335/2012[H3N8]), which is phylogenetically related to equine influenza A(H3N8) viruses and probably represents natural horse-to-camel transmission. C1 [Yondon, Myagmarsukh; Zayat, Batsukh] Inst Vet Med, Ulaanbaatar, Mongol Peo Rep. [Nelson, Martha I.] NIH, Bethesda, MD 20892 USA. [Heil, Gary L.; Anderson, Benjamin D.; White, Sarah K.; Gray, Gregory C.] Univ Florida, Gainesville, FL USA. [Lin, Xudong; Halpin, Rebecca A.; Wentworth, David E.] J Craig Venter Inst, Rockville, MD USA. [McKenzie, Pamela P.] St Jude Childrens Res Hosp, Memphis, TN 38105 USA. RP Gray, GC (reprint author), Univ Florida, Coll Publ Hlth & Hlth Profess, Box 100188, Gainesville, FL 32610 USA. EM gcgray@phhp.ufl.edu OI Wentworth, David/0000-0002-5190-980X FU National Institute of Allergy and Infectious Diseases, National Institutes of Health, Department of Health and Human Services, USA [HH-SN266200700005C, HHSN272200900007C]; National Institute of Allergy and Infectious Diseases [R01 AI068803-ARRA]; US Department of Defense Armed Forces Health Surveillance Center, Global Emerging Infections Surveillance and Response Program; Office of Global Affairs at the Department of Health and Human Services FX This research was supported by multiple grants: contracts HH-SN266200700005C (St. Jude Children's Research Hospital) and HHSN272200900007C (J. Craig Venter Institute) from the National Institute of Allergy and Infectious Diseases, National Institutes of Health, Department of Health and Human Services, USA; R01 AI068803-ARRA supplement (G.C.G.) from the National Institute of Allergy and Infectious Diseases; and multiple grants (G.C.G.) from the US Department of Defense Armed Forces Health Surveillance Center, Global Emerging Infections Surveillance and Response Program. This research was conducted within the context of the Multinational Influenza Seasonal Mortality Study, an ongoing international collaborative effort to understand influenza epidemiology and evolution, led by the Fogarty International Center, National Institutes of Health, with funding from the Office of Global Affairs at the Department of Health and Human Services (M.I.N.). NR 15 TC 6 Z9 7 U1 0 U2 6 PU CENTERS DISEASE CONTROL PI ATLANTA PA 1600 CLIFTON RD, ATLANTA, GA 30333 USA SN 1080-6040 EI 1080-6059 J9 EMERG INFECT DIS JI Emerg. Infect. Dis PD DEC PY 2014 VL 20 IS 12 BP 2144 EP 2147 DI 10.3201/eid2012.140435 PG 4 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA AU6RP UT WOS:000345729900033 PM 25418532 ER PT J AU Wall, EH Hewitt, SC Case, LK Lin, CY Korach, KS Teuscher, C AF Wall, Emma H. Hewitt, Sylvia C. Case, Laure K. Lin, Chin-Yo Korach, Kenneth S. Teuscher, Cory TI The role of genetics in estrogen responses: a critical piece of an intricate puzzle SO FASEB JOURNAL LA English DT Review DE genotype; reproductive tissue ID MAMMARY-GLAND DEVELOPMENT; ESTRADIOL-REGULATED RESPONSES; QUANTITATIVE TRAIT LOCI; BREAST-CANCER CELLS; X ACI INTERCROSS; RECEPTOR-ALPHA; FEMALE MICE; IN-VIVO; OPPOSITE-SEX; BISPHENOL-A AB The estrogens are female sex hormones that are involved in a variety of physiological processes, including reproductive development and function, wound healing, and bone growth. They are mainly known for their roles in reproductive tissues-specifically, 17 beta-estradiol (E-2), the primary estrogen, which is secreted by the ovaries and induces cellular proliferation and growth of the uterus and mammary glands. In addition to the role of estrogens in promoting tissue growth and development during normal physiological states, they have a well-established role in determining susceptibility to disease, particularly cancer, in reproductive tissues. The responsiveness of various tissues to estrogen is genetically controlled, with marked quantitative variation observed across multiple species, including humans. This variation presents both researchers and clinicians with a veritable physiological puzzle, the pieces of which-many of them unknown-are complex and difficult to fit together. Although genetics is known to play a major role in determining sensitivity to estrogens, there are other factors, including parent of origin and the maternal environment, that are intimately linked to heritable phenotypes but do not represent genotype, per se. The objectives of this review article were to summarize the current knowledge of the role of genotype, and uterine and neonatal environments, in phenotypic variation in the response to estrogens; to discuss recent findings and the potential mechanisms involved; and to highlight exciting research opportunities for the future. C1 [Wall, Emma H.; Case, Laure K.; Teuscher, Cory] Univ Vermont, Dept Med & Pathol, Burlington, VT 05405 USA. [Hewitt, Sylvia C.; Korach, Kenneth S.] US Natl Inst Hlth, Natl Inst Environm Hlth Sci, Res Triangle Pk, NC USA. [Lin, Chin-Yo] Univ Houston, Ctr Nucl Receptors & Cell Signaling, Houston, TX USA. RP Teuscher, C (reprint author), Univ Vermont, C331 Given Med Bldg, Burlington, VT 05405 USA. EM c.teuscher@uvm.edu OI Korach, Kenneth/0000-0002-7765-418X FU Intramural Research Program of the U.S. National Institutes of Health, National Institute of Environmental Health Sciences grant [Z01ES70065] FX This research was supported, in part, by the Intramural Research Program of the U.S. National Institutes of Health, National Institute of Environmental Health Sciences grant Z01ES70065. NR 137 TC 4 Z9 4 U1 0 U2 7 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 EI 1530-6860 J9 FASEB J JI Faseb J. PD DEC PY 2014 VL 28 IS 12 BP 5042 EP 5054 DI 10.1096/fj.14-260307 PG 13 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA AU9EN UT WOS:000345894500003 PM 25212221 ER PT J AU Usadi, RS Alvero, R Armstrong, AY Rebar, RW DeCherney, AH Maddox, YT AF Usadi, Rebecca S. Alvero, Ruben Armstrong, Alicia Y. Rebar, Robert W. DeCherney, Alan H. Maddox, Yvonne T. TI Keeping clinicians in research: the Clinical Research/Reproductive Scientist Training Program (CREST) strategy, 2006-2012 SO FERTILITY AND STERILITY LA English DT Editorial Material C1 [Usadi, Rebecca S.] North Carolinas Healthcare Syst, Carolinas Healthcare Reprod Med & Infertil, Charlotte, NC 28204 USA. [Alvero, Ruben] Univ Colorado, Dept Obstet & Gynecol, Div Reprod Endocrinol & Infertil, Denver, CO 80202 USA. [Armstrong, Alicia Y.; DeCherney, Alan H.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Program Reprod & Adult Endocrinol, NIH, Bethesda, MD USA. [Rebar, Robert W.] Western Michigan Univ, Homer Stryker MD Sch Med, Dept Obstet & Gynecol, Kalamazoo, MI 49008 USA. [Rebar, Robert W.] Michigan State Univ, Coll Human Med, Dept Obstet Gynecol & Reprod Biol, Grand Rapids, MI USA. [Rebar, Robert W.] Univ Alabama Birmingham, Dept Obstet & Gynecol, Birmingham, AL 35294 USA. [Maddox, Yvonne T.] Natl Inst Minor Hlth & Hlth Dispar, NIH, Bethesda, MD USA. RP Usadi, RS (reprint author), North Carolinas Healthcare Syst, Carolinas Healthcare Reprod Med & Infertil, Charlotte, NC 28204 USA. NR 5 TC 0 Z9 0 U1 0 U2 3 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0015-0282 EI 1556-5653 J9 FERTIL STERIL JI Fertil. Steril. PD DEC PY 2014 VL 102 IS 6 BP 1542 EP 1544 DI 10.1016/j.fertnstert.2014.09.002 PG 3 WC Obstetrics & Gynecology; Reproductive Biology SC Obstetrics & Gynecology; Reproductive Biology GA AU4YF UT WOS:000345613600008 PM 25439798 ER PT J AU Cote, LR Bornstein, MH AF Cote, Linda R. Bornstein, Marc H. TI Productive vocabulary among three groups of bilingual American children: Comparison and prediction SO FIRST LANGUAGE LA English DT Article DE Bilingual; development; English; immigrant; Japanese; Korean; language; Spanish; toddlers; vocabulary ID DUAL LANGUAGE EXPOSURE; EXPRESSIVE VOCABULARY; FIT INDEXES; TODDLERS; VALIDITY; ENGLISH; SPANISH; INFANTS; PARENT; INPUT AB The importance of input factors for bilingual children's vocabulary development was investigated. Forty-seven Argentine, 42 South Korean, 51 European American, 29 Latino immigrant, 26 Japanese immigrant, and 35 Korean immigrant mothers completed checklists of their 20-month-old children's productive vocabularies. Bilingual children's vocabulary sizes in each language separately were consistently smaller than their monolingual peers but only Latino bilingual children had smaller total vocabularies than monolingual children. Bilingual children's vocabulary sizes were similar to each other. Maternal acculturation predicted the amount of input in each language, which then predicted children's vocabulary size in each language. Maternal acculturation also predicted children's English-language vocabulary size directly. C1 [Cote, Linda R.] Marymount Univ, Arlington, VA 22207 USA. [Cote, Linda R.; Bornstein, Marc H.] NIH, Bethesda, MD USA. RP Cote, LR (reprint author), Marymount Univ, Dept Psychol, 2807 N Glebe Rd, Arlington, VA 22207 USA. EM linda.cote-reilly@marymount.edu FU Intramural NIH HHS [ZIA HD001119-27] NR 58 TC 4 Z9 4 U1 1 U2 9 PU SAGE PUBLICATIONS LTD PI LONDON PA 1 OLIVERS YARD, 55 CITY ROAD, LONDON EC1Y 1SP, ENGLAND SN 0142-7237 EI 1740-2344 J9 FIRST LANG JI First Lang. PD DEC PY 2014 VL 34 IS 6 BP 467 EP 485 DI 10.1177/0142723714560178 PG 19 WC Psychology, Developmental; Linguistics; Language & Linguistics SC Psychology; Linguistics GA AU9NX UT WOS:000345922000001 PM 25620820 ER PT J AU Steinberg, KM Schneider, VA Graves-Lindsay, TA Fulton, RS Agarwala, R Huddleston, J Shiryev, SA Morgulis, A Surti, U Warren, WC Church, DM Eichler, EE Wilson, RK AF Steinberg, Karyn Meltz Schneider, Valerie A. Graves-Lindsay, Tina A. Fulton, Robert S. Agarwala, Richa Huddleston, John Shiryev, Sergey A. Morgulis, Aleksandr Surti, Urvashi Warren, Wesley C. Church, Deanna M. Eichler, Evan E. Wilson, Richard K. TI Single haplotype assembly of the human genome from a hydatidiform mole SO GENOME RESEARCH LA English DT Article ID COPY-NUMBER VARIATION; SEGMENTAL DUPLICATIONS; STRUCTURAL VARIATION; BREAKPOINT REGION; SEQUENCE; MAP; DIVERSITY; EVOLUTION; GENES; ISOCHROMOSOME AB A complete reference assembly is essential for accurately interpreting individual genomes and associating variation with phenotypes. While the current human reference genome sequence is of very high quality, gaps and misassemblies remain due to biological and technical complexities. Large repetitive sequences and complex allelic diversity are the two main drivers of assembly error. Although increasing the length of sequence reads and library fragments can improve assembly, even the longest available reads do not resolve all regions. In order to overcome the issue of allelic diversity, we used genomic DNA from an essentially haploid hydatidiform mole, CHM1. We utilized several resources from this DNA including a set of end-sequenced and indexed BAC clones and 100x Illumina whole-genome shotgun (WGS) sequence coverage. We used the WGS sequence and the GRCh37 reference assembly to create an assembly of the CHM1 genome. We subsequently incorporated 382 finished BAC clone sequences to generate a draft assembly, CHM_11.1(NCBI AssemblyDB GCA_000306695.2). Analysis of gene, repetitive element, and segmental duplication content show this assembly to be of excellent quality and contiguity. However, comparison to assembly-independent resources, such as BAC clone end sequences and PacBio long reads, indicate misassembled regions. Most of these regions are enriched for structural variation and segmental duplication, and can be resolved in the future. This publicly available assembly will be integrated into the Genome Reference Consortium curation framework for further improvement, with the ultimate goal being a completely finished gap-free assembly. C1 [Steinberg, Karyn Meltz; Graves-Lindsay, Tina A.; Fulton, Robert S.; Warren, Wesley C.; Wilson, Richard K.] Washington Univ, Genome Inst, St Louis, MO 63108 USA. [Schneider, Valerie A.; Agarwala, Richa; Shiryev, Sergey A.; Morgulis, Aleksandr] NIH, Natl Ctr Biotechnol Informat, Natl Lib Med, Bethesda, MD 20894 USA. [Huddleston, John; Eichler, Evan E.] Univ Washington, Dept Genome Sci, Seattle, WA 98195 USA. [Huddleston, John; Eichler, Evan E.] Univ Washington, Howard Hughes Med Inst, Seattle, WA 98795 USA. [Surti, Urvashi] Univ Pittsburgh, Dept Pathol & Human Genet, Pittsburgh, PA 15260 USA. [Church, Deanna M.] Personalis Inc, Menlo Pk, CA 94025 USA. RP Wilson, RK (reprint author), Washington Univ, Genome Inst, St Louis, MO 63108 USA. EM rwilson@genome.wustl.edu OI Meltz Steinberg, Karyn/0000-0002-8676-3337 FU NIH [2R01HG002385, 5P01HG004120] FX We thank Pieter de Jong for the creation of the CHORI-17 BAG library used extensively in this project. We acknowledge Nathan Bouk for his expertise in sequence alignment and insightful discussions of alignment data. We acknowledge the efforts of the production and finishing groups at The Genome Institute, particularly Aye Wollom, Susie Rock, Milinn Kremitzki, and Derek Albrecht. We are greatly appreciative of BioNano Genomics and Dr. Pui Kwok for generously sharing the genomic map and alignments to the CHM1_1.1 assembly. E.E.E. is an investigator of the Howard Hughes Medical Institute. This work was supported by NIH Grants 2R01HG002385 and 5P01HG004120 to E.E.E. NR 49 TC 17 Z9 17 U1 1 U2 8 PU COLD SPRING HARBOR LAB PRESS, PUBLICATIONS DEPT PI COLD SPRING HARBOR PA 1 BUNGTOWN RD, COLD SPRING HARBOR, NY 11724 USA SN 1088-9051 EI 1549-5469 J9 GENOME RES JI Genome Res. PD DEC PY 2014 VL 24 IS 12 BP 2066 EP 2076 DI 10.1101/gr.180893.114 PG 11 WC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity GA AU7XB UT WOS:000345810600015 PM 25373144 ER PT J AU Aka, P Emmanuel, B Vila, MC Jariwala, A Nkrumah, F Periago, MV Neequaye, J Kiruthu, C Levine, PH Biggar, RJ Bhatia, K Bethony, JM Mbulaiteye, SM AF Aka, Peter Emmanuel, Benjamin Vila, Maria Candida Jariwala, Amar Nkrumah, Francis Periago, Maria V. Neequaye, Janet Kiruthu, Christine Levine, Paul H. Biggar, Robert J. Bhatia, Kishor Bethony, Jeffrey M. Mbulaiteye, Sam M. TI Elevated serum levels of interleukin-6 in endemic Burkitt lymphoma in Ghana SO HEMATOLOGICAL ONCOLOGY LA English DT Letter ID EPSTEIN-BARR-VIRUS; MALARIA C1 [Aka, Peter; Emmanuel, Benjamin; Kiruthu, Christine; Bhatia, Kishor; Mbulaiteye, Sam M.] NCI, Div Canc Epidemiol & Genet, DCEG, Bethesda, MD 20892 USA. [Vila, Maria Candida; Jariwala, Amar; Periago, Maria V.; Levine, Paul H.; Bethony, Jeffrey M.] George Washington Univ, Dept Microbiol & Trop Med, Washington, DC USA. [Nkrumah, Francis] Noguchi Mem Inst, Accra, Ghana. [Neequaye, Janet] Korle Bu Univ, Teaching Hosp Accra, Dept Child Hlth, Accra, Ghana. [Biggar, Robert J.] Queensland Univ Technol, Inst Hlth & Biotechnol, Brisbane, Qld 4001, Australia. RP Aka, P (reprint author), NCI, Div Canc Epidemiol & Genet, DCEG, Bethesda, MD 20892 USA. EM mbulaits@mail.nih.gov OI Periago, Maria Victoria/0000-0002-1470-5146 FU Intramural NIH HHS [Z99 CA999999]; NCI NIH HHS [N01CO12400, N01-CO-12400] NR 13 TC 0 Z9 0 U1 0 U2 2 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0278-0232 EI 1099-1069 J9 HEMATOL ONCOL JI Hematol. Oncol. PD DEC PY 2014 VL 32 IS 4 BP 218 EP 220 DI 10.1002/hon.2121 PG 3 WC Oncology; Hematology SC Oncology; Hematology GA AU9LL UT WOS:000345914200009 PM 24493366 ER PT J AU Hou, YA Wu, XM Hallett, M Chan, P Wu, T AF Hou, Yanan Wu, Xuemin Hallett, Mark Chan, Piu Wu, Tao TI Frequency-Dependent Neural Activity in Parkinson's Disease SO HUMAN BRAIN MAPPING LA English DT Article DE functional MRI; amplitude of low frequency fluctuation; frequency band; midbrain; basal ganglia ID EXTERNALLY TRIGGERED MOVEMENTS; SPONTANEOUS BRAIN ACTIVITY; STATE FUNCTIONAL MRI; CEREBRAL-BLOOD-FLOW; BASAL GANGLIA; REGIONAL HOMOGENEITY; RED NUCLEUS; PREFRONTAL CORTEX; SUBSTANTIA-NIGRA; PYRAMIDAL TRACT AB The brainstem and basal ganglia are important in the pathophysiology of Parkinson's disease (PD). Reliable and sensitive detection of neural activity changes in these regions should be helpful in scientific and clinical research on PD. In this study, we used resting state functional MRI and amplitude of low frequency fluctuation (ALFF) methods to examine spontaneous neural activity in 109 patients with PD. We examined activity in two frequency bands, slow-4 (between 0.027 and 0.073 Hz) and slow-5 (0.010-0.027 Hz). Patients had decreased ALFF in the striatum and increased ALFF in the midbrain, and changes were more significant in slow-4. Additionally, changes in slow-4 in both basal ganglia and midbrain correlated with the severity of the parkinsonism. The ALFF in the caudate nucleus positively correlated with the dose of levodopa, while the ALFF in the putamen negatively correlated with the disease duration in both slow-4 and slow-5 bands. In addition, the ALFF in the rostral supplementary motor area negatively correlated with bradykinesia subscale scores. Our findings show that with a large cohort of patients and distinguishing frequency bands, neural modulations in the brainstem and striatum in PD can be detected and may have clinical relevance. The physiological interpretation of these changes needs to be determined. Hum Brain Mapp 35:5815-5833, 2014. (c) 2014 Wiley Periodicals, Inc. C1 [Hou, Yanan; Wu, Xuemin; Chan, Piu; Wu, Tao] Capital Med Univ, Dept Neurobiol, Key Lab Neurodegenerat Disorders, Minist Educ,Beijing Inst Geriatr,Xuanwu Hosp, Beijing 100053, Peoples R China. [Hou, Yanan; Wu, Xuemin; Chan, Piu; Wu, Tao] Beijing Inst Brain Disorders, Beijing Key Lab Parkinsons Dis, Parkinson Dis Ctr, Beijing, Peoples R China. [Hallett, Mark] NINDS, Human Motor Control Sect, Med Neurol Branch, NIH, Bethesda, MD 20892 USA. RP Wu, T (reprint author), Capital Med Univ, Dept Neurobiol, Key Lab Neurodegenerat Disorders, Minist Educ,Beijing Inst Geriatr,Xuanwu Hosp, Beijing 100053, Peoples R China. EM wutao69@gmail.com FU National Science Foundation of China [30870693, 81071012, 81271429]; NINDS Intramural Program FX Contract grant sponsor: National Science Foundation of China; Contract grant numbers: 30870693; 81071012; and 81271429; Contract grant sponsor: NINDS Intramural Program (to Dr. Hallett). NR 63 TC 14 Z9 16 U1 1 U2 15 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1065-9471 EI 1097-0193 J9 HUM BRAIN MAPP JI Hum. Brain Mapp. PD DEC PY 2014 VL 35 IS 12 BP 5815 EP 5833 DI 10.1002/hbm.22587 PG 19 WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA AS6WA UT WOS:000344398900007 PM 25045127 ER PT J AU Tinaz, S Belluscio, BA Malone, P van der Veen, JW Hallett, M Horovitz, SG AF Tinaz, Sule Belluscio, Beth A. Malone, Patrick van der Veen, Jan Willem Hallett, Mark Horovitz, Silvina G. TI Role of the Sensorimotor Cortex in Tourette Syndrome using Multimodal Imaging SO HUMAN BRAIN MAPPING LA English DT Article DE gamma-aminobutyric acid; magnetic resonance spectroscopy; functional magnetic resonance imaging; magnetoencephalography; resting state; functional connectivity; beta oscillations ID IN-VIVO NEUROCHEMISTRY; HUMAN CEREBRAL-CORTEX; TIC GENERATION; INSULA; SYSTEM; DISORDER; SCALE; BODY; INDIVIDUALS; ABNORMALITY AB Tourette syndrome (TS) is a neuropsychiatric disorder characterized by motor and vocal tics. Most patients describe uncomfortable premonitory sensations preceding the tics and a subjective experience of increased sensitivity to tactile stimuli. These reports indicate that a sensory processing disturbance is an important component of TS together with motor phenomena. Thus, we focused our investigation on the role of the sensorimotor cortex (SMC) in TS using multimodal neuroimaging techniques. We measured the gamma-aminobutyric acid (GABA)+/Creatine (Cre) ratio in the SMC using GABA H-1 magnetic resonance spectroscopy. We recorded the baseline beta activity in the SMC using magnetoencephalography and correlated GABA+/Cre ratio with baseline beta band power. Finally, we examined the resting state functional connectivity (FC) pattern of the SMC using functional magnetic resonance imaging (fMRI). GABA+/Cre ratio in the SMC did not differ between patients and controls. Correlation between the baseline beta band power and GABA+/Cre ratio was abnormal in patients. The anterior insula showed increased FC with the SMC in patients. These findings suggest that altered limbic input to the SMC and abnormal GABA-mediated beta oscillations in the SMC may underpin some of the sensorimotor processing disturbances in TS and contribute to tic generation. Hum Brain Mapp 35:5834-5846, 2014. Published 2014. This article is a U.S. Government work and is in the public domain in the USA. C1 [Tinaz, Sule; Belluscio, Beth A.; Malone, Patrick; Hallett, Mark; Horovitz, Silvina G.] NINDS, Human Motor Control Sect, NIH, Bethesda, MD 20892 USA. [van der Veen, Jan Willem] NIMH, Magnet Resonance Spect Core, NIH, Bethesda, MD 20892 USA. RP Tinaz, S (reprint author), 10 Ctr Dr MSC 1428,Bldg 10,Room 7D42, Bethesda, MD 20892 USA. EM aysesule.tinaz@nih.gov FU NINDS FX Contract grant sponsor: NINDS Intramural Research Program NR 48 TC 15 Z9 15 U1 2 U2 6 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1065-9471 EI 1097-0193 J9 HUM BRAIN MAPP JI Hum. Brain Mapp. PD DEC PY 2014 VL 35 IS 12 BP 5834 EP 5846 DI 10.1002/hbm.22588 PG 13 WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA AS6WA UT WOS:000344398900008 PM 25044024 ER PT J AU Hamann, JM Dayan, E Hummel, FC Cohen, LG AF Hamann, Janne M. Dayan, Eran Hummel, Friedhelm C. Cohen, Leonardo G. TI Baseline Frontostriatal-Limbic Connectivity Predicts Reward-Based Memory Formation SO HUMAN BRAIN MAPPING LA English DT Article DE reward learning; brain connectivity; learning; memory; resting state functional magnetic resonance imaging; ventral striatum ID INTRINSIC FUNCTIONAL CONNECTIVITY; HUMAN NUCLEUS-ACCUMBENS; DEFAULT-MODE NETWORK; RESTING STATE FMRI; LONG-TERM-MEMORY; MOTOR SKILL; CORRELATION-COEFFICIENT; DOPAMINERGIC MIDBRAIN; NEURAL MECHANISMS; MONETARY REWARD AB Reward mediates the acquisition and long-term retention of procedural skills in humans. Yet, learning under rewarded conditions is highly variable across individuals and the mechanisms that determine interindividual variability in rewarded learning are not known. We postulated that baseline functional connectivity in a large-scale frontostriatal-limbic network could predict subsequent interindividual variability in rewarded learning. Resting-state functional MRI was acquired in two groups of subjects (n=30) who then trained on a visuomotor procedural learning task with or without reward feedback. We then tested whether baseline functional connectivity within the frontostriatal-limbic network predicted memory strength measured immediately, 24 h and 1 month after training in both groups. We found that connectivity in the frontostriatal-limbic network predicted interindividual variability in the rewarded but not in the unrewarded learning group. Prediction was strongest for long-term memory. Similar links between connectivity and reward-based memory were absent in two control networks, a fronto-parieto-temporal language network and the dorsal attention network. The results indicate that baseline functional connectivity within the frontostriatal-limbic network successfully predicts long-term retention of rewarded learning. Hum Brain Mapp 35:5921-5931, 2014. (c) 2014 Wiley Periodicals, Inc. C1 [Hamann, Janne M.; Dayan, Eran; Cohen, Leonardo G.] NINDS, Human Cort Physiol & Neurorehabil Sect, NIH, Bethesda, MD 20892 USA. [Hamann, Janne M.; Hummel, Friedhelm C.] Univ Med Ctr Hamburg Eppendorf, BrainImaging & NeuroStimulat BINS Lab, D-20251 Hamburg, Germany. RP Dayan, E (reprint author), NINDS, Human Cort Physiol & Neurorehabil Sect, NIH, Bldg 10, Bethesda, MD 20892 USA. EM dayane@ninds.nih.gov OI Dayan, Eran/0000-0001-9710-9210 FU Intramural Research Program of the National Institute of Neurological Disorders and Stroke at the National Institutes of Health and by the Mentoring Program for Excellent Students of the University Medical Center Hamburg-Eppendorf; Scholarship from Claussen-Simon Stiftung FX Contract grant sponsor(s): Intramural Research Program of the National Institute of Neurological Disorders and Stroke at the National Institutes of Health and by the Mentoring Program for Excellent Students of the University Medical Center Hamburg-Eppendorf (to JMH); Scholarship from Claussen-Simon Stiftung (to JMH). NR 85 TC 2 Z9 2 U1 2 U2 8 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1065-9471 EI 1097-0193 J9 HUM BRAIN MAPP JI Hum. Brain Mapp. PD DEC PY 2014 VL 35 IS 12 BP 5921 EP 5931 DI 10.1002/hbm.22594 PG 11 WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA AS6WA UT WOS:000344398900014 PM 25078102 ER PT J AU Eddin, AS Wang, J Wu, WS Sargolzaei, S Bjornson, B Jones, RA Gaillard, WD Adjouadi, M AF Eddin, Anas Salah Wang, Jin Wu, Wensong Sargolzaei, Saman Bjornson, Bruce Jones, Richard A. Gaillard, William D. Adjouadi, Malek TI The Effects of Pediatric Epilepsy on a Language Connectome SO HUMAN BRAIN MAPPING LA English DT Article DE functional network; language network; graph theory; functional magnetic resonance imaging; independent component analysis ID TEMPORAL-LOBE EPILEPSY; INDEPENDENT COMPONENT ANALYSIS; LOCALIZATION-RELATED EPILEPSY; SMALL-WORLD ORGANIZATION; DEFAULT-MODE NETWORK; FUNCTIONAL CONNECTIVITY; RESTING-STATE; BRAIN NETWORKS; IMPAIRED ATTENTION; ATYPICAL LANGUAGE AB This study introduces a new approach for assessing the effects of pediatric epilepsy on a language connectome. Two novel data-driven network construction approaches are presented. These methods rely on connecting different brain regions using either extent or intensity of language related activations as identified by independent component analysis of fMRI. An auditory word definition decision task paradigm was used to activate the language network for 29 patients and 30 controls. Evaluations illustrated that pediatric epilepsy is associated with a network efficiency reduction. Patients showed a propensity to inefficiently use the whole brain network to perform the language task; whereas, controls seemed to efficiently use smaller segregated network components to achieve the same task. To explain the causes of the decreased efficiency, graph theoretical analysis was performed. The analysis revealed substantial global network feature differences between the patients and controls for the extent of activation network. It also showed that for both subject groups the language network exhibited small-world characteristics; however, the patient's extent of activation network showed a tendency toward randomness. It was also shown that the intensity of activation network displayed ipsilateral hub reorganization on the local level. We finally showed that a clustering scheme was able to fairly separate the subjects into their respective patient or control groups. The clustering was initiated using local and global nodal measurements. Compared to the intensity of activation network, the extent of activation network clustering demonstrated better precision. This ascertained that the network differences presented by the networks were associated with pediatric epilepsy. Hum Brain Mapp 35:5996-6010, 2014. (c) 2014 Wiley Periodicals, Inc. C1 [Eddin, Anas Salah] Florida Polytech Univ, Dept Comp Sci & Informat Technol, Lakeland, FL USA. [Eddin, Anas Salah; Wang, Jin; Sargolzaei, Saman; Adjouadi, Malek] Florida Int Univ, Dept Elect & Comp Engn, Miami, FL 33174 USA. [Wu, Wensong] Florida Int Univ, Dept Math & Stat, Miami, FL 33174 USA. [Bjornson, Bruce] British Columbia Childrens Hosp, Div Neurol, Vancouver, BC V6H 3V4, Canada. [Jones, Richard A.] Childrens Healthcare Atlanta, Dept Radiol, Atlanta, GA USA. [Jones, Richard A.] Emory Univ, Dept Radiol, Atlanta, GA 30322 USA. [Gaillard, William D.] George Washington Univ, Childrens Natl Med Ctr, Dept Neurosci, Washington, DC USA. [Gaillard, William D.] NINDS, Clin Epilepsy Sect, NIH, Bethesda, MD 20892 USA. [Adjouadi, Malek] Florida Int Univ, Dept Biomed Engn, Miami, FL 33174 USA. RP Adjouadi, M (reprint author), Florida Int Univ, Coll Engn & Comp, 10555 W Flagler St,EC 2672, Miami, FL 33174 USA. EM adjouadi@fiu.edu RI Bjornson, Bruce/A-8616-2010 OI Bjornson, Bruce/0000-0002-1465-6196 FU National Science Foundation [CNS-0959985, CNS-1042341, HRD-0833093, IIP-1230661]; National Institutes of Health [NINDS R01 NS44280, NCRR M01RR020359]; Intellectual and Developmental Research Center [HD040677-07]; Ware Foundation; joint Neuro-Engineering Program; Miami Children's Hospital FX Contract grant sponsor: National Science Foundation; Contract grant numbers: CNS-0959985; CNS-1042341; HRD-0833093; and IIP-1230661; Contract grant sponsor: National Institutes of Health; Contract grant numbers: NINDS R01 NS44280; NCRR M01RR020359; Contract grant sponsor: Intellectual and Developmental Research Center; Contract grant number: HD040677-07; Contract grant sponsor: Ware Foundation and the joint Neuro-Engineering Program with Miami Children's Hospital. NR 82 TC 1 Z9 1 U1 1 U2 15 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1065-9471 EI 1097-0193 J9 HUM BRAIN MAPP JI Hum. Brain Mapp. PD DEC PY 2014 VL 35 IS 12 BP 5996 EP 6010 DI 10.1002/hbm.22600 PG 15 WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA AS6WA UT WOS:000344398900020 PM 25082062 ER PT J AU Mansoor, A Bagci, U Xu, ZY Foster, B Olivier, KN Elinoff, JM Suffredini, AF Udupa, JK Mollura, DJ AF Mansoor, Awais Bagci, Ulas Xu, Ziyue Foster, Brent Olivier, Kenneth N. Elinoff, Jason M. Suffredini, Anthony F. Udupa, Jayaram K. Mollura, Daniel J. TI A Generic Approach to Pathological Lung Segmentation SO IEEE TRANSACTIONS ON MEDICAL IMAGING LA English DT Article DE Anatomy-guided segmentation; computed tomography; fuzzy connectedness; pathological lung segmentation; random forest ID COMPUTER-AIDED DIAGNOSIS; CT IMAGES; FUZZY CONNECTEDNESS; THORACIC CT; AUTOMATIC SEGMENTATION; ATTENUATION VALUES; LOBE SEGMENTATION; GROUND-GLASS; ATLAS; CLASSIFICATION AB In this study, we propose a novel pathological lung segmentation method that takes into account neighbor prior constraints and a novel pathology recognition system. Our proposed framework has two stages; during stage one, we adapted the fuzzy connectedness (FC) image segmentation algorithm to perform initial lung parenchyma extraction. In parallel, we estimate the lung volume using rib-cage information without explicitly delineating lungs. This rudimentary, but intelligent lung volume estimation system allows comparison of volume differences between rib cage and FC based lung volume measurements. Significant volume difference indicates the presence of pathology, which invokes the second stage of the proposed framework for the refinement of segmented lung. In stage two, texture-based features are utilized to detect abnormal imaging patterns (consolidations, ground glass, interstitial thickening, tree-inbud, honeycombing, nodules, and micro-nodules) that might have been missed during the first stage of the algorithm. This refinement stage is further completed by a novel neighboring anatomy-guided segmentation approach to include abnormalities with weak textures, and pleura regions. We evaluated the accuracy and efficiency of the proposed method on more than 400 CT scans with the presence of a wide spectrum of abnormalities. To our best of knowledge, this is the first study to evaluate all abnormal imaging patterns in a single segmentation framework. The quantitative results show that our pathological lung segmentation method improves on current standards because of its high sensitivity and specificity and may have considerable potential to enhance the performance of routine clinical tasks. C1 [Mansoor, Awais; Bagci, Ulas; Xu, Ziyue; Foster, Brent; Mollura, Daniel J.] NIH, Dept Radiol & Imaging Sci, Bethesda, MD 20892 USA. [Elinoff, Jason M.; Suffredini, Anthony F.] NIH, Dept Crit Care Med, Ctr Clin, Bethesda, MD 20892 USA. [Olivier, Kenneth N.] NIAID, Immunopathogenesis Sect, Lab Clin Infect Dis, NIH, Bethesda, MD 20892 USA. [Udupa, Jayaram K.] Univ Penn, Dept Radiol, Philadelphia, PA 19104 USA. RP Mansoor, A (reprint author), NIH, Dept Radiol & Imaging Sci, Bldg 10, Bethesda, MD 20892 USA. EM ulasbagci@gmail.com OI Bagci, Ulas/0000-0001-7379-6829 FU Center for Infectious Disease Imaging (CIDI); National Institute of Allergy and Infectious Diseases (NIAID); National Institute of Biomedical Imaging and Bioengineering (NIBIB) FX This work was supported by Center for Infectious Disease Imaging (CIDI), the intramural research program of the National Institute of Allergy and Infectious Diseases (NIAID), and the National Institute of Biomedical Imaging and Bioengineering (NIBIB). Asterisk indicates corresponding author. NR 61 TC 21 Z9 22 U1 4 U2 24 PU IEEE-INST ELECTRICAL ELECTRONICS ENGINEERS INC PI PISCATAWAY PA 445 HOES LANE, PISCATAWAY, NJ 08855-4141 USA SN 0278-0062 EI 1558-254X J9 IEEE T MED IMAGING JI IEEE Trans. Med. Imaging PD DEC PY 2014 VL 33 IS 12 BP 2293 EP 2310 DI 10.1109/TMI.2014.2337057 PG 18 WC Computer Science, Interdisciplinary Applications; Engineering, Biomedical; Engineering, Electrical & Electronic; Imaging Science & Photographic Technology; Radiology, Nuclear Medicine & Medical Imaging SC Computer Science; Engineering; Imaging Science & Photographic Technology; Radiology, Nuclear Medicine & Medical Imaging GA AU9JC UT WOS:000345907400006 PM 25020069 ER PT J AU Trinchieri, G AF Trinchieri, G. TI Cancer as a disease of the metaorganism SO IMMUNOLOGY LA English DT Meeting Abstract C1 [Trinchieri, G.] NCI, Canc & Inflammat Program, Frederick, MD 21701 USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0019-2805 EI 1365-2567 J9 IMMUNOLOGY JI Immunology PD DEC PY 2014 VL 143 SU 2 SI SI MA 93 BP 13 EP 13 PG 1 WC Immunology SC Immunology GA AU6GT UT WOS:000345702600030 ER PT J AU Ombrello, MJ AF Ombrello, M. J. TI Genetically-complex autoinflammatory diseases: Still's disease and Behcet's disease SO IMMUNOLOGY LA English DT Meeting Abstract C1 [Ombrello, M. J.] NIAMSD, Translat Genet & Genom Unit, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 2 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0019-2805 EI 1365-2567 J9 IMMUNOLOGY JI Immunology PD DEC PY 2014 VL 143 SU 2 SI SI MA 109 BP 34 EP 34 PG 1 WC Immunology SC Immunology GA AU6GT UT WOS:000345702600076 ER PT J AU Kolev, M Dimeloe, S Le Friec, G Arbore, G Povoleri, GA Fischer, M Razik, L Watson, J Couzi, L Afzali, B Lavender, P Hess, C Kemper, C AF Kolev, M. Dimeloe, S. Le Friec, G. Arbore, G. Povoleri, G. A. Fischer, M. Razik, L. Watson, J. Couzi, L. Afzali, B. Lavender, P. Hess, C. Kemper, C. TI CD46 links complement and metabolic reprogramming in human Th1 responses SO IMMUNOLOGY LA English DT Meeting Abstract C1 [Kolev, M.; Le Friec, G.; Arbore, G.; Povoleri, G. A.; Afzali, B.; Kemper, C.] Kings Coll London, MRC, Ctr Transplantat, Div Transplant Immunol & Mucosal Biol, London, England. [Dimeloe, S.; Fischer, M.; Razik, L.; Hess, C.] Univ Basel, Dept Biomed, Basel, Switzerland. [Povoleri, G. A.; Afzali, B.] Kings Hlth Partners, Biomed Res Ctr, London, England. [Watson, J.; Lavender, P.] Kings Coll London, MRC, London, England. [Watson, J.; Lavender, P.] Kings Coll London, Asthma UK Ctr Allerg Mech Asthma, London, England. [Couzi, L.] CHU Bordeaux, Hosp Pellegrin, CNRS, UMR 1564, Bordeaux, France. [Afzali, B.] NIAMSD, Mol Immunol & Inflammat Branch, NIH, Bethesda, MD 20892 USA. RI Kemper, Claudia/B-1502-2015; kolev, mihail/D-1476-2015 OI kolev, mihail/0000-0002-5226-4759 NR 0 TC 0 Z9 0 U1 0 U2 1 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0019-2805 EI 1365-2567 J9 IMMUNOLOGY JI Immunology PD DEC PY 2014 VL 143 SU 2 SI SI MA 613 BP 49 EP 49 PG 1 WC Immunology SC Immunology GA AU6GT UT WOS:000345702600110 ER PT J AU Galloway, A Hodson, D Bell, L Saveliev, A Lukasiak, S Turner, M AF Galloway, A. Hodson, D. Bell, L. Saveliev, A. Lukasiak, S. Turner, M. TI The RNA-binding proteins ZFP36L1 and ZFP36L2 are essential for the development of B lymphocytes SO IMMUNOLOGY LA English DT Meeting Abstract C1 [Galloway, A.; Bell, L.; Saveliev, A.; Lukasiak, S.; Turner, M.] Babraham Inst, LLSD, Cambridge, England. [Hodson, D.] NCI, Ctr Canc Res, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0019-2805 EI 1365-2567 J9 IMMUNOLOGY JI Immunology PD DEC PY 2014 VL 143 SU 2 SI SI MA 489 BP 73 EP 73 PG 1 WC Immunology SC Immunology GA AU6GT UT WOS:000345702600186 ER PT J AU Dutzan, N Abusleme, L Bouladoux, N Greenwell-Wild, T Betts, K Belkaid, Y Moutsopoulos, N Konkel, JE AF Dutzan, N. Abusleme, L. Bouladoux, N. Greenwell-Wild, T. Betts, K. Belkaid, Y. Moutsopoulos, N. Konkel, J. E. TI Tissue-specific control of immune responses in the oral mucosa SO IMMUNOLOGY LA English DT Meeting Abstract C1 [Dutzan, N.; Abusleme, L.; Greenwell-Wild, T.; Betts, K.; Moutsopoulos, N.] NIDCR, NIH, Bethesda, MD USA. [Bouladoux, N.; Belkaid, Y.] NIAID, NIH, Bethesda, MD 20892 USA. [Konkel, J. E.] Univ Manchester, Manchester, Lancs, England. NR 0 TC 0 Z9 0 U1 0 U2 1 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0019-2805 EI 1365-2567 J9 IMMUNOLOGY JI Immunology PD DEC PY 2014 VL 143 SU 2 SI SI MA 560 BP 75 EP 75 PG 1 WC Immunology SC Immunology GA AU6GT UT WOS:000345702600193 ER PT J AU Whibley, N Mamo, A Coleman, B Conti, H Traggiai, E Kolbinger, F Vogel, B Kammuller, M Siebenlist, U Iwakura, Y Gaffen, S AF Whibley, N. Mamo, A. Coleman, B. Conti, H. Traggiai, E. Kolbinger, F. Vogel, B. Kammuller, M. Siebenlist, U. Iwakura, Y. Gaffen, S. TI Differential requirements of IL-17 family cytokines in anti-fungal immunity against oral candidiasis SO IMMUNOLOGY LA English DT Meeting Abstract C1 [Whibley, N.; Mamo, A.; Coleman, B.; Conti, H.; Gaffen, S.] Univ Pittsburgh, Pittsburgh, PA USA. [Traggiai, E.; Kolbinger, F.; Vogel, B.; Kammuller, M.] Novartis Inst Biomed Res, Basel, Switzerland. [Siebenlist, U.] NIAID, NIH, Bethesda, MD 20892 USA. [Iwakura, Y.] Tokyo Univ Sci, Chiba, Japan. RI Iwakura, Yoichiro/E-5457-2011 OI Iwakura, Yoichiro/0000-0002-9934-5775 NR 0 TC 0 Z9 0 U1 0 U2 1 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0019-2805 EI 1365-2567 J9 IMMUNOLOGY JI Immunology PD DEC PY 2014 VL 143 SU 2 SI SI MA 433 BP 86 EP 86 PG 1 WC Immunology SC Immunology GA AU6GT UT WOS:000345702600232 ER PT J AU Askenase, MH Byrd, AL Bouladoux, N da Fonseca, DM Konkel, JE Belkaid, Y Grainger, JR AF Askenase, M. H. Byrd, A. L. Bouladoux, N. da Fonseca, D. Morais Konkel, J. E. Belkaid, Y. Grainger, J. R. TI Education of monocyte precursors instructs for regulatory function at barrier sites during infection SO IMMUNOLOGY LA English DT Meeting Abstract C1 [Askenase, M. H.; Byrd, A. L.; Bouladoux, N.; da Fonseca, D. Morais; Belkaid, Y.; Grainger, J. R.] NIAID, Program Barrier Immun & Repair, Mucosal Immunol Sect, LPD,NIH, Bethesda, MD 20892 USA. Univ Penn, Immunol Grad Grp, Philadelphia, PA 19104 USA. NHGRI, Translat & Funct Genom Branch, NIH, Bethesda, MD 20892 USA. [Konkel, J. E.] MCCIR, Manchester, Lancs, England. Univ Manchester, Fac Life Sci, Manchester, Lancs, England. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0019-2805 EI 1365-2567 J9 IMMUNOLOGY JI Immunology PD DEC PY 2014 VL 143 SU 2 SI SI MA 532 BP 104 EP 104 PG 1 WC Immunology SC Immunology GA AU6GT UT WOS:000345702600295 ER PT J AU Sansom, DM Schubert, D Bode, C Kenefeck, R Hou, T Wing, J Kennedy, A Unger, S Bulashevska, A Gruning, B Petersen, B Schaffer, A Frede, N Dueckers, G Seneviratne, S Kanariou, M Rensing-Ehl, A Salzer, U Warnatz, K Cathomen, T Emmerich, F Fisch, P Rakhmanov, M Franke, A Sakaguchi, S Walker, LS Grimbacher, B AF Sansom, D. M. Schubert, D. Bode, C. Kenefeck, R. Hou, T. Wing, J. Kennedy, A. Unger, S. Bulashevska, A. Gruning, B. Petersen, B. Schaffer, A. Frede, N. Dueckers, G. Seneviratne, S. Kanariou, M. Rensing-Ehl, A. Salzer, U. Warnatz, K. Cathomen, T. Emmerich, F. Fisch, P. Rakhmanov, M. Franke, A. Sakaguchi, S. Walker, L. S. Grimbacher, B. TI Heterozygous mutations in CTLA-4 are associated with defective regulatory T-cell function, causing an immune dysregulation syndrome in humans SO IMMUNOLOGY LA English DT Meeting Abstract CT Annual Congress of the British-Society-for-Immunology CY DEC 01-04, 2014 CL Brighton, ENGLAND SP British Soc Immunol C1 [Sansom, D. M.; Schubert, D.; Bode, C.; Kenefeck, R.; Hou, T.; Kennedy, A.; Kanariou, M.; Emmerich, F.; Fisch, P.; Walker, L. S.; Grimbacher, B.] UCL, Inst Immun & Transplantat, London, 20892, England. [Unger, S.; Bulashevska, A.; Frede, N.; Rensing-Ehl, A.; Salzer, U.; Warnatz, K.; Cathomen, T.; Rakhmanov, M.] Univ Med Ctr, Ctr Chron Immunodeficiency, Freiburg, Germany. Univ Freiburg, Spemann Grad Sch Biol & Med, Freiburg NW3 2QG, Germany. [Wing, J.; Sakaguchi, S.] Osaka Univ, Dept Expt Immunol, Osaka, Japan. [Gruning, B.] Univ Freiburg, Dept Comp Sci, Freiburg, Germany. [Petersen, B.; Franke, A.] Univ Kiel, Inst Clin Mol Biol, Kiel, Germany. [Schaffer, A.] NIH, Bethesda, MD USA. [Dueckers, G.] Childrens Hosp Krefeld, Krefeld, Germany. [Seneviratne, S.] Royal Free Hosp, Dept Immunol, London, England. AS Childrens Hosp, Dept Immunol & Histocompatibil, Athens, Greece. Univ Med Ctr, Dept Transfus Med, Freiburg, Germany. Univ Med Ctr, Dept Pathol, Freiburg, Germany. RI HOU, TIEZHENG/B-4848-2015 NR 0 TC 0 Z9 0 U1 0 U2 1 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0019-2805 EI 1365-2567 J9 IMMUNOLOGY JI Immunology PD DEC PY 2014 VL 143 SU 2 SI SI MA 329 BP 155 EP 155 PG 1 WC Immunology SC Immunology GA AU6GT UT WOS:000345702600470 ER PT J AU Williams, EL Dhanda, A Liu, B Lait, PJP Schewitz-Bowers, LP Collins, P Dick, AD Nussenblatt, RB Lee, RWJ AF Williams, E. L. Dhanda, A. Liu, B. Lait, P. J. P. Schewitz-Bowers, L. P. Collins, P. Dick, A. D. Nussenblatt, R. B. Lee, R. W. J. CA UNITE Human Ocular Immunology TI CD14(++)CD16(+) monocytes are enriched in inflammatory diseases and promote the sensitivity of T-cells to corticosteroids SO IMMUNOLOGY LA English DT Meeting Abstract C1 [Williams, E. L.; Dhanda, A.; Lait, P. J. P.; Schewitz-Bowers, L. P.; Dick, A. D.; Lee, R. W. J.] Univ Bristol, Sch Clin Sci, Bristol, Avon, England. Moorfields Eye Hosp, Natl Inst Hlth Res NIHR Biomed Res Ctr, London, England. UCL, Inst Ophthalmol, London, England. [Collins, P.] Univ Hosp Bristol NHS Fdn Trust, Bristol, Avon, England. [Liu, B.; Nussenblatt, R. B.] NEI, Immunol Lab, NIH, Bethesda, MD 20892 USA. NIH, Natl Ctr Complementary & Alternat Med, Bethesda, MD 20892 USA. NIH, Ctr Human Immunol Autoimmun & Inflammat, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0019-2805 EI 1365-2567 J9 IMMUNOLOGY JI Immunology PD DEC PY 2014 VL 143 SU 2 SI SI MA 357 BP 157 EP 158 PG 2 WC Immunology SC Immunology GA AU6GT UT WOS:000345702600477 ER PT J AU Lait, PJP Schewitz-Bowers, LP Copland, DA Chen, P Vistica, B Dhanda, A Liu, B Jawad, S Li, Z Hirani, S Wu, W Sen, HN Conway-Campbell, B Wei, L Gery, I Dick, AD Lee, RWJ Nussenblatt, RB AF Lait, P. J. P. Schewitz-Bowers, L. P. Copland, D. A. Chen, P. Vistica, B. Dhanda, A. Liu, B. Jawad, S. Li, Z. Hirani, S. Wu, W. Sen, H. Nida Conway-Campbell, B. Wei, L. Gery, I. Dick, A. D. Lee, R. W. J. Nussenblatt, R. B. CA UNITE Human Ocular Immunolgy Cons TI Corticosteroid resistant Th17 cells are sensitive to calcineurin inhibition SO IMMUNOLOGY LA English DT Meeting Abstract C1 [Lait, P. J. P.; Schewitz-Bowers, L. P.; Copland, D. A.; Dhanda, A.; Conway-Campbell, B.; Dick, A. D.; Lee, R. W. J.] Univ Bristol, Sch Clin Sci, Bristol, Avon, England. Moorfields Eye Hosp, Natl Inst Hlth Res, Biomed Res Ctr, London, England. UCL, Inst Ophthalmol, London, England. [Chen, P.; Vistica, B.; Liu, B.; Jawad, S.; Li, Z.; Hirani, S.; Wu, W.; Sen, H. Nida; Wei, L.; Gery, I.; Nussenblatt, R. B.] NEI, Immunol Lab, NIH, Bethesda, MD 20892 USA. Univ Hosp Bristol NHS Fdn Trust, Bristol, Avon, England. NIH, Natl Ctr Complementary & Alternat Med, Bethesda, MD 20892 USA. NIH, Ctr Human Immunol Autoimmun & Inflammat, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0019-2805 EI 1365-2567 J9 IMMUNOLOGY JI Immunology PD DEC PY 2014 VL 143 SU 2 SI SI MA 428 BP 161 EP 161 PG 1 WC Immunology SC Immunology GA AU6GT UT WOS:000345702600490 ER PT J AU Persaud, D Patel, K Karalius, B Rainwater-Lovett, K Ziemniak, C Ellis, A Chen, YH Richman, D Siberry, GK Van Dyke, RB Burchett, S Seage, GR Luzuriaga, K AF Persaud, Deborah Patel, Kunjal Karalius, Brad Rainwater-Lovett, Kaitlin Ziemniak, Carrie Ellis, Angela Chen, Ya Hui Richman, Douglas Siberry, George K. Van Dyke, Russell B. Burchett, Sandra Seage, George R., III Luzuriaga, Katherine CA Pediat HIV AIDS Cohort Study TI Influence of Age at Virologic Control on Peripheral Blood Human Immunodeficiency Virus Reservoir Size and Serostatus in Perinatally Infected Adolescents SO JAMA PEDIATRICS LA English DT Article ID PRIMARY HIV-1 INFECTION; ACTIVE ANTIRETROVIRAL THERAPY; HIV-1-INFECTED CHILDREN; MICROBIAL TRANSLOCATION; GASTROINTESTINAL-TRACT; IMMUNE ACTIVATION; VIRAL RESERVOIRS; SOLUBLE CD14; INFANTS; PERSISTENCE AB IMPORTANCE Combination antiretroviral therapy initiated within several weeks of human immunodeficiency virus (HIV) infection in adults limits proviral reservoirs that preclude HIV cure. Biomarkers of restricted proviral reservoirs may aid in the monitoring of HIV remission or cure. OBJECTIVES To quantify peripheral blood proviral reservoir size in perinatally HIV-infected (PHIV+) adolescents and to identify correlates of limited proviral reservoirs. DESIGN, SETTING, AND PARTICIPANTS A cross-sectional study including 144 PHIV+ youths (median age, 14.3 years) enrolled in the United States-based Pediatric HIV/AIDS Cohort Study and receiving durable (median duration, 10.2 years) combination antiretroviral therapy, stratified by age at virologic control. MAIN OUTCOMES AND MEASURES The primary end pointwas peripheral blood mononuclear cell (PBMC) proviral load after virologic control at different ages. Correlations between proviral load and markers of active HIV production (ie, HIV-specific antibodies, 2-long terminal repeat circles) and markers of immune activation and inflammation were also assessed. RESULTS Proviral reservoir size was markedly reduced in the PHIV+ youth who achieved virologic control before 1 year of age (4.2 [interquartile range, 2.6-8.6] copies per 1 million PBMCs) compared with those who achieved virologic control at 1 to 5 years of age (19.4 [interquartile range, 5.5-99.8] copies per 1 million PBMCs) or after 5 years of age (70.7 [interquartile range, 23.2-209.4] copies per 1 million PBMCs; P < .001). A proviral burden of less than 10 copies per 1 million PBMCs in PHIV+ youth was measured in 11 (79%), 20 (40%), and 13 (18%) participants with virologic control before 1 year, at 1 to 5 years, and after 5 years of age, respectively (P < .001). Lower proviral load was associated with undetectable 2-long terminal repeat circles (P < .001) and HIV-negative or indeterminate serostatus (P < .001) but not with concentrations of soluble immune activation markers CD14 and CD163. CONCLUSIONS AND RELEVANCE Early effective combination antiretroviral therapy with prolonged virologic suppression after perinatal HIV infection leads to negligible peripheral blood proviral reservoirs in adolescence and is associated with negative or indeterminate HIV serostatus. These findings highlight the long-term effect of early effective control of HIV replication on biomarkers of HIV persistence in perinatal infection and the utility of HIV serostatus as a biomarker for small proviral reservoir size, although not necessarily for cure. C1 [Persaud, Deborah; Rainwater-Lovett, Kaitlin; Ziemniak, Carrie; Chen, Ya Hui] Johns Hopkins Univ, Sch Med, Dept Pediat, Baltimore, MD 21287 USA. [Patel, Kunjal; Karalius, Brad; Seage, George R., III] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. [Patel, Kunjal; Karalius, Brad; Seage, George R., III] Harvard Univ, Sch Publ Hlth, Ctr Biostat AIDS Res, Boston, MA 02115 USA. [Ellis, Angela] Frontier Sci & Technol Res Fdn Inc, Buffalo, NY USA. [Richman, Douglas] Univ Calif San Diego, Dept Pathol, La Jolla, CA 92093 USA. [Richman, Douglas] Vet Affairs San Diego Healthcare Syst, San Diego, CA USA. [Siberry, George K.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Maternal & Pediat Infect Dis Branch, Bethesda, MD USA. [Van Dyke, Russell B.] Tulane Univ, Sch Med, Dept Pediat, New Orleans, LA 70112 USA. [Burchett, Sandra] Boston Childrens Hosp, Div Infect Dis, Boston, MA USA. [Luzuriaga, Katherine] Univ Massachusetts, Sch Med, Dept Pediat, Program Mol Med, Worcester, MA USA. [Luzuriaga, Katherine] Univ Massachusetts, Sch Med, Ctr Clin & Translat Sci, Worcester, MA USA. RP Persaud, D (reprint author), Johns Hopkins Univ, Sch Med, Dept Pediat, 720 Rutland Ave,Ross Bldg,Room 1170, Baltimore, MD 21287 USA. EM dpers@jhmi.edu FU National Institutes of Health (NIH) [R01HD080474, R21AI100656]; American Foundation for AIDS Research; International Maternal Pediatric Adolescent AIDS Clinical Trials Network (Dr Persaud) [UO1-AI-068632]; Johns Hopkins University Center for AIDS Research [P30-AI094189]; Eunice Kennedy Shriver National Institute of Child Health and Human Development; National Institute on Drug Abuse; National Institute of Allergy and Infectious Diseases; Office of AIDS Research; National Institute of Mental Health; National Institute of Neurological and Communicative Disorders and Stroke; National Institute on Deafness and Other Communication Disorders; National Heart, Lung, and Blood Institute; National Institute of Dental and Craniofacial Research; National Institute on Alcohol Abuse and Alcoholism [HD052102, 3 U01 HD052102-05S1, 3 U01 HD052102-06S3]; Harvard School of Public Health; Tulane University School of Medicine [HD052104, 3U01 HD052104-06S1]; Collaboratory for AIDS Research on Eradication (CARE) [U19 AI096113]; University of California; San Diego; Center for AIDS Research; James Pendleton Charitable Trust FX The laboratory studies were supported by grants R01HD080474 and R21AI100656 from the National Institutes of Health (NIH) (Dr Persaud); by funding from the American Foundation for AIDS Research (Drs Persaud and Luzuriaga); and by grants U01-AI-068632 from the International Maternal Pediatric Adolescent AIDS Clinical Trials Network (Dr Persaud) and P30-AI094189 from the Johns Hopkins University Center for AIDS Research (Dr Persaud). The study was also supported by the Eunice Kennedy Shriver National Institute of Child Health and Human Development with cofunding from the National Institute on Drug Abuse, the National Institute of Allergy and Infectious Diseases, the Office of AIDS Research, the National Institute of Mental Health, the National Institute of Neurological and Communicative Disorders and Stroke, the National Institute on Deafness and Other Communication Disorders, the National Heart, Lung, and Blood Institute, the National Institute of Dental and Craniofacial Research, and the National Institute on Alcohol Abuse and Alcoholism through cooperative agreements HD052102, 3 U01 HD052102-05S1, and 3 U01 HD052102-06S3 with the Harvard School of Public Health (principal investigator [PI], George R. Seage III, DSc, MPH; project director, Julie Alperen, DrPH) and HD052104 and 3U01 HD052104-06S1 from the Tulane University School of Medicine (PI, Russell B. Van Dyke, MD; co-PI, Kenneth Rich, MD; project director, Patrick Davis, BS). Dr Richman was supported by grant U19 AI096113 from the Collaboratory for AIDS Research on Eradication (CARE), grant AI306214 from the University of California, San Diego, Center for AIDS Research, and the James Pendleton Charitable Trust. Data management services were provided by Frontier Science and Technology Research Foundation (PI, Suzanne Siminski, MS, MBA), and regulatory services and logistical support were provided byWestat, Inc (PI, Julie Davidson, MSN). NR 39 TC 17 Z9 17 U1 1 U2 5 PU AMER MEDICAL ASSOC PI CHICAGO PA 330 N WABASH AVE, STE 39300, CHICAGO, IL 60611-5885 USA SN 2168-6203 EI 2168-6211 J9 JAMA PEDIATR JI JAMA Pediatr. PD DEC PY 2014 VL 168 IS 12 BP 1138 EP 1146 DI 10.1001/jamapediatrics.2014.1560 PG 9 WC Pediatrics SC Pediatrics GA AU9GO UT WOS:000345900000012 PM 25286283 ER PT J AU Vanicek, T Spies, M Rami-Mark, C Savli, M Hoflich, A Kranz, GS Hahn, A Kutzelnigg, A Traub-Weidinger, T Mitterhauser, M Wadsak, W Hacker, M Volkow, ND Kasper, S Lanzenberger, R AF Vanicek, Thomas Spies, Marie Rami-Mark, Christina Savli, Markus Hoeflich, Anna Kranz, Georg S. Hahn, Andreas Kutzelnigg, Alexandra Traub-Weidinger, Tatjana Mitterhauser, Markus Wadsak, Wolfgang Hacker, Marcus Volkow, Nora D. Kasper, Siegfried Lanzenberger, Rupert TI The Norepinephrine Transporter in Attention-Deficit/Hyperactivity Disorder Investigated With Positron Emission Tomography SO JAMA PSYCHIATRY LA English DT Article ID DEFICIT-HYPERACTIVITY DISORDER; NONHUMAN PRIMATE BRAIN; DOPAMINE TRANSPORTER; EXTRACELLULAR DOPAMINE; PREFRONTAL CORTEX; IN-VIVO; ORAL METHYLPHENIDATE; LOCUS-COERULEUS; NAIVE ADULTS; PET AB IMPORTANCE Attention-deficit/hyperactivity disorder (ADHD) research has long focused on the dopaminergic system's contribution to pathogenesis, although the results have been inconclusive. However, a case has been made for the involvement of the noradrenergic system, which modulates cognitive processes, such as arousal, working memory, and response inhibition, all of which are typically affected in ADHD. Furthermore, the norepinephrine transporter (NET) is an important target for frequently prescribed medication in ADHD. Therefore, the NET is suggested to play a critical role in ADHD. OBJECTIVE To explore the differences in NET nondisplaceable binding potential (NET BPND) using positron emission tomography and the highly selective radioligand (S,S)-[F-18]FMeNER-D-2 [(S,S)-2-(alpha-(2-[F-18]fluoro[H-2(2)]methoxyphenoxy)benzyl)morpholine] between adults with ADHD and healthy volunteers serving as controls. DESIGN, SETTING, AND PARTICIPANTS Twenty-two medication-free patients with ADHD (mean [SD] age, 30.7[10.4] years; 15[68%] men) without psychiatric comorbidities and 22 age-and sex-matched healthy controls (30.9[10.6] years; 15[68%] men) underwent positron emission tomography once. A linear mixed model was used to compare NET BPND between groups. MAIN OUTCOMES AND MEASURES The NET BPND in selected regions of interest relevant for ADHD, including the hippocampus, putamen, pallidum, thalamus, midbrain with pons (comprising a region of interest that includes the locus coeruleus), and cerebellum. In addition, the NET BPND was evaluated in thalamic subnuclei (13 atlas-based regions of interest). RESULTS We found no significant differences in NET availability or regional distribution between patients with ADHD and healthy controls in all investigated brain regions (F-1,F-41 < 0.01; P = .96). Furthermore, we identified no significant association between ADHD symptom severity and regional NET availability. Neither sex nor smoking status influenced NET availability. We determined a significant negative correlation between age and NET availability in the thalamus (R-2 = 0.29; P < .01 corrected) and midbrain with pons, including the locus coeruleus (R-2 = 0.18; P < .01 corrected), which corroborates prior findings of a decrease in NET availability with aging in the human brain. CONCLUSIONS AND RELEVANCE Our results do not indicate involvement of changes in brain NET availability or distribution in the pathogenesis of ADHD. However, the noradrenergic transmitter system may be affected on a different level, such as in cortical regions, which cannot be reliably quantified with this positron emission tomography ligand. Alternatively, different key proteins of noradrenergic neurotransmission might be affected. C1 [Vanicek, Thomas; Spies, Marie; Savli, Markus; Hoeflich, Anna; Kranz, Georg S.; Hahn, Andreas; Kutzelnigg, Alexandra; Kasper, Siegfried; Lanzenberger, Rupert] Med Univ Vienna, Dept Psychiat & Psychotherapy, A-1090 Vienna, Austria. [Rami-Mark, Christina; Traub-Weidinger, Tatjana; Mitterhauser, Markus; Wadsak, Wolfgang; Hacker, Marcus] Med Univ Vienna, Dept Biomed Imaging & Image Guided Therapy, Div Nucl Med, A-1090 Vienna, Austria. [Volkow, Nora D.] NIAAA, NIH, Bethesda, MD USA. RP Lanzenberger, R (reprint author), Med Univ Vienna, Dept Psychiat & Psychotherapy, Funct Mol & Translat Neuroimaging Lab, Waehringer Guertel 18-20, A-1090 Vienna, Austria. EM rupert.lanzenberger@meduniwien.ac.at OI Hahn, Andreas/0000-0001-9727-7580 FU Austrian Science Fund (FWF) [P22981] FX This research was supported by grant P22981 from the Austrian Science Fund (FWF) (Dr Lanzenberger). NR 76 TC 10 Z9 10 U1 5 U2 13 PU AMER MEDICAL ASSOC PI CHICAGO PA 330 N WABASH AVE, STE 39300, CHICAGO, IL 60611-5885 USA SN 2168-622X EI 2168-6238 J9 JAMA PSYCHIAT JI JAMA Psychiatry PD DEC PY 2014 VL 71 IS 12 BP 1340 EP 1349 DI 10.1001/jamapsychiatry.2014.1226 PG 10 WC Psychiatry SC Psychiatry GA AU9MQ UT WOS:000345917900006 PM 25338091 ER PT J AU Correll, CU Robinson, DG Schooler, NR Brunette, MF Mueser, KT Rosenheck, RA Marcy, P Addington, J Estroff, SE Robinson, J Penn, DL Azrin, S Goldstein, A Severe, J Heinssen, R Kane, JM AF Correll, Christoph U. Robinson, Delbert G. Schooler, Nina R. Brunette, Mary F. Mueser, Kim T. Rosenheck, Robert A. Marcy, Patricia Addington, Jean Estroff, Sue E. Robinson, James Penn, David L. Azrin, Susan Goldstein, Amy Severe, Joanne Heinssen, Robert Kane, John M. TI Cardiometabolic Risk in Patients With First-Episode Schizophrenia Spectrum Disorders Baseline Results From the RAISE-ETP Study SO JAMA PSYCHIATRY LA English DT Article ID NUTRITION EXAMINATION SURVEY; 3RD NATIONAL-HEALTH; DENSITY-LIPOPROTEIN CHOLESTEROL; RANDOMIZED CLINICAL-TRIAL; FASTING PLASMA-GLUCOSE; UNITED-STATES; METABOLIC SYNDROME; MENTAL-ILLNESS; ANTIPSYCHOTIC-DRUGS; SCHIZOAFFECTIVE DISORDER AB IMPORTANCE The fact that individuals with schizophrenia have high cardiovascular morbidity and mortality is well established. However, risk status and moderators or mediators in the earliest stages of illness are less clear. OBJECTIVE To assess cardiometabolic risk in first-episode schizophrenia spectrum disorders (FES) and its relationship to illness duration, antipsychotic treatment duration and type, sex, and race/ethnicity. DESIGN, SETTING, AND PARTICIPANTS Baseline results of the Recovery After an Initial Schizophrenia Episode (RAISE) study, collected between July 22, 2010, and July 5, 2012, from 34 community mental health facilities without major research, teaching, or clinical FES programs. Patients were aged 15 to 40 years, had research-confirmed diagnoses of FES, and had less than 6 months of lifetime antipsychotic treatment. EXPOSURE Prebaseline antipsychotic treatment was based on the community clinician's and/or patient's decision. MAIN OUTCOMES AND MEASURES Body composition and fasting lipid, glucose, and insulin parameters. RESULTS In 394 of 404 patients with cardiometabolic data (mean [SD] age, 23.6 [5.0] years; mean [SD] lifetime antipsychotic treatment, 47.3 [46.1] days), 48.3% were obese or overweight, 50.8% smoked, 56.5% had dyslipidemia, 39.9% had prehypertension, 10.0% had hypertension, and 13.2% had metabolic syndrome. Prediabetes (glucose based, 4.0%; hemoglobin A(1c) based, 15.4%) and diabetes (glucose based, 3.0%; hemoglobin A1c based, 2.9%) were less frequent. Total psychiatric illness duration correlated significantly with higher body mass index, fat mass, fat percentage, and waist circumference (all P < .01) but not elevated metabolic parameters (except triglycerides to HDL-C ratio [P = .04]). Conversely, antipsychotic treatment duration correlated significantly with higher non-HDL-C, triglycerides, and triglycerides to HDL-C ratio and lower HDL-C and systolic blood pressure (all P <= .01). Olanzapine was significantly associated with higher triglycerides, insulin, and insulin resistance, whereas quetiapine fumarate was associated with significantly higher triglycerides to HDL-C ratio (all P <= .02). CONCLUSIONS AND RELEVANCE In patients with FES, cardiometabolic risk factors and abnormalities are present early in the illness and likely related to the underlying illness, unhealthy lifestyle, and antipsychotic medications, which interact with each other. Prevention of and early interventions for psychiatric illness and treatment with lower-risk agents, routine antipsychotic adverse effect monitoring, and smoking cessation interventions are needed from the earliest illness phases. C1 [Correll, Christoph U.; Robinson, Delbert G.; Schooler, Nina R.; Marcy, Patricia; Kane, John M.] Zucker Hillside Hosp, North Shore LIJ Hlth Syst, Div Psychiat Res, Glen Oaks, NY 11004 USA. [Correll, Christoph U.; Robinson, Delbert G.; Marcy, Patricia; Kane, John M.] Feinstein Inst Med Res, Manhasset, NY USA. [Correll, Christoph U.; Robinson, Delbert G.; Robinson, James; Kane, John M.] Hofstra North Shore LIJ Sch Med, Hempstead, NY USA. [Correll, Christoph U.; Robinson, Delbert G.; Kane, John M.] Albert Einstein Coll Med, Bronx, NY 10467 USA. [Schooler, Nina R.] Suny Downstate Med Ctr, New York, NY USA. [Brunette, Mary F.] Geisel Sch Med Dartmouth, Hanover, NH USA. [Brunette, Mary F.] Dept Hlth & Human Serv, Bur Behav Hlth, Hanover, NH USA. [Mueser, Kim T.] Boston Univ, Ctr Psychiat Rehabil, Dept Occupat Therapy, Boston, MA 02215 USA. [Mueser, Kim T.] Boston Univ, Ctr Psychiat Rehabil, Dept Psychiat, Boston, MA 02215 USA. [Mueser, Kim T.] Boston Univ, Ctr Psychiat Rehabil, Dept Psychol, Boston, MA 02215 USA. [Rosenheck, Robert A.] Yale Univ, Dept Psychiat & Epidemiol, Princeton, NJ USA. [Rosenheck, Robert A.] Yale Univ, Dept Publ Hlth, Princeton, NJ USA. [Addington, Jean] Univ Calgary, Hotchkiss Brain Inst, Dept Psychiat, Calgary, AB, Canada. [Estroff, Sue E.] Univ N Carolina, Dept Social Med, Chapel Hill, NC USA. [Robinson, James] Nathan S Kline Inst Psychiat Res, Orangeburg, NY USA. [Penn, David L.] Univ N Carolina, Dept Psychol, Chapel Hill, NC USA. [Azrin, Susan; Goldstein, Amy; Severe, Joanne; Heinssen, Robert] NIMH, Bethesda, MD 20892 USA. RP Correll, CU (reprint author), Zucker Hillside Hosp, North Shore LIJ Hlth Syst, Div Psychiat Res, 75-59 263rd St, Glen Oaks, NY 11004 USA. EM ccorrell@lij.edu FU National Institute of Mental Health [HHSN-271-2009-00019C]; American Recovery and Reinvestment Act FX This work was supported in part by grant HHSN-271-2009-00019C from the National Institute of Mental Health (Dr Kane) and by federal funds from the American Recovery and Reinvestment Act. NR 79 TC 71 Z9 73 U1 7 U2 22 PU AMER MEDICAL ASSOC PI CHICAGO PA 330 N WABASH AVE, STE 39300, CHICAGO, IL 60611-5885 USA SN 2168-622X EI 2168-6238 J9 JAMA PSYCHIAT JI JAMA Psychiatry PD DEC PY 2014 VL 71 IS 12 BP 1350 EP 1363 DI 10.1001/jamapsychiatry.2014.1314 PG 14 WC Psychiatry SC Psychiatry GA AU9MQ UT WOS:000345917900007 PM 25321337 ER PT J AU Duverger, O Ohara, T Shaffer, JR Donahue, D Zerfas, P Dullnig, A Crecelius, C Beniash, E Marazita, ML Morasso, MI AF Duverger, Olivier Ohara, Takahiro Shaffer, John R. Donahue, Danielle Zerfas, Patricia Dullnig, Andrew Crecelius, Christopher Beniash, Elia Marazita, Mary L. Morasso, Maria I. TI Hair keratin mutations in tooth enamel increase dental decay risk SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Article ID TUFT PROTEIN; CARIES; MATRIX; MORPHOGENESIS; DETERMINANTS; DISORDER; TEETH; K6HF AB Tooth enamel is the hardest substance in the human body and has a unique combination of hardness and fracture toughness that protects teeth from dental caries, the most common chronic disease worldwide. In addition to a high mineral content, tooth enamel comprises organic material that is important for mechanical performance and influences the initiation and progression of caries; however, the protein composition of tooth enamel has not been fully characterized. Here, we determined that epithelial hair keratins, which are crucial for maintaining the integrity of the sheaths that support the hair shaft, are expressed in the enamel organ and are essential organic components of mature enamel. Using genetic and intraoral examination data from 386 children and 706 adults, we found that individuals harboring known hair disorder-associated polymorphisms in the gene encoding keratin 75 (KRT75), KRT75(A161T) and KRT75(E337K), are prone to increased dental caries. Analysis of teeth from individuals carrying the KRT75(A161T) variant revealed an altered enamel structure and a marked reduction of enamel hardness, suggesting that a functional keratin network is required for the mechanical stability of tooth enamel. Taken together, our results identify a genetic locus that influences enamel structure and establish a connection between hair disorders and susceptibility to dental caries. C1 [Duverger, Olivier; Ohara, Takahiro; Morasso, Maria I.] NIAMSD, Skin Biol Lab, NIAMS, NIH, Bethesda, MD USA. [Shaffer, John R.; Marazita, Mary L.] Univ Pittsburgh, Dept Human Genet, Pittsburgh, PA USA. [Donahue, Danielle] NINDS, Mouse Imaging Facil, NIH, Bethesda, MD 20892 USA. [Zerfas, Patricia] NIH, Off Res Serv, Div Vet Resources, Bethesda, MD 20892 USA. [Dullnig, Andrew; Crecelius, Christopher] Walter Reed Natl Mil Med Ctr, Natl Capital Consortium Oral & Maxillofacial Surg, Bethesda, MD USA. [Beniash, Elia; Marazita, Mary L.] Univ Pittsburgh, Dept Oral Biol, Pittsburgh, PA USA. [Beniash, Elia] Univ Pittsburgh, Ctr Craniofacial Regenerat, Pittsburgh, PA USA. [Marazita, Mary L.] Univ Pittsburgh, Ctr Craniofacial & Dent Genet, Pittsburgh, PA USA. [Marazita, Mary L.] Univ Pittsburgh, Clin & Translat Sci Inst, Pittsburgh, PA USA. RP Morasso, MI (reprint author), Skin Biol Lab, 50 South Dr,Room 1523, Bethesda, MD 20892 USA. EM morasso@nih.gov FU Intramural Research Program of NIAMS [ZIA AR041171-07]; National Institute of Dental and Craniofacial Research [R01-DE014899, U01-DE018903, R56-DE016703] FX This work was supported by the Intramural Research Program of NIAMS (ZIA AR041171-07 to M.I. Morasso) and by grants from the National Institute of Dental and Craniofacial Research (R01-DE014899 and U01-DE018903 to M.L. Marazita and R56-DE016703 to E. Beniash). We thank Paul Bible, Meghan Kellett, Julie Erthal, and Juliane Lessard from the Laboratory of Skin Biology. We thank members of NIAMS: Martha Somerman, Leon Nesti, Gustavo Gutierrez-Cruz, Hong-Wei Sun, and the Light Imaging Facility. We thank Glen Imamura and the residents at the Walter Reed National Military Medical Center; Yang Xu, Toshiki Soejima, and Robert J. Weyant from the University of Pittsburgh; Daniel W. McNeil and Richard Crout from West Virginia University; Jiang Chen and Dennis Roop from the University of Colorado Denver. We would like to express our gratitude to the COHRA participants and field research teams whose contributions made this work possible. NR 32 TC 5 Z9 5 U1 1 U2 22 PU AMER SOC CLINICAL INVESTIGATION INC PI ANN ARBOR PA 35 RESEARCH DR, STE 300, ANN ARBOR, MI 48103 USA SN 0021-9738 EI 1558-8238 J9 J CLIN INVEST JI J. Clin. Invest. PD DEC PY 2014 VL 124 IS 12 BP 5219 EP 5224 DI 10.1172/JCI78272 PG 6 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA AU5XP UT WOS:000345677200015 PM 25347471 ER PT J AU Chang, J Lee, S Blackstone, C AF Chang, Jaerak Lee, Seongju Blackstone, Craig TI Spastic paraplegia proteins spastizin and spatacsin mediate autophagic lysosome reformation SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Article ID NEURODEGENERATIVE DISEASE; SPG11; LOCALIZATION; CYTOKINESIS; BIOGENESIS; MECHANISM; ENDOSOME; MTOR; MICE AB Autophagy allows cells to adapt to changes in their environment by coordinating the degradation and recycling of cellular components and organelles to maintain homeostasis. Lysosomes are organelles critical for terminating autophagy via their fusion with mature autophagosomes to generate autolysosomes that degrade autophagic materials; therefore, maintenance of the lysosomal population is essential for autophagy-dependent cellular clearance. Here, we have demonstrated that the two most common autosomal recessive hereditary spastic paraplegia gene products, the SPG15 protein spastizin and the SPG11 protein spatacsin, are pivotal for autophagic lysosome reformation (ALR), a pathway that generates new lysosomes. Lysosomal targeting of spastizin required an intact FYVE domain, which binds phosphatidylinositol 3-phosphate. Loss of spastizin or spatacsin resulted in depletion of free lysosomes, which are competent to fuse with autophagosomes, and an accumulation of autolysosomes, reflecting a failure in ALR. Moreover, spastizin and spatacsin were essential components for the initiation of lysosomal tubulation. Together, these results link dysfunction of the autophagy/lysosomal biogenesis machinery to neurodegeneration. C1 [Chang, Jaerak; Lee, Seongju; Blackstone, Craig] NINDS, Cell Biol Sect, Neurogenet Branch, NIH, Bethesda, MD 20892 USA. RP Blackstone, C (reprint author), NINDS, Neurogenet Branch, NIH Bldg 35,Room 2C-913,9000 Rockville Pike, Bethesda, MD 20892 USA. EM blackstc@ninds.nih.gov FU Intramural Research Program of the National Institute of Neurological Disorders and Stroke, NIH FX This work was supported by the Intramural Research Program of the National Institute of Neurological Disorders and Stroke, NIH. NR 41 TC 26 Z9 26 U1 0 U2 8 PU AMER SOC CLINICAL INVESTIGATION INC PI ANN ARBOR PA 35 RESEARCH DR, STE 300, ANN ARBOR, MI 48103 USA SN 0021-9738 EI 1558-8238 J9 J CLIN INVEST JI J. Clin. Invest. PD DEC PY 2014 VL 124 IS 12 BP 5249 EP 5262 DI 10.1172/JCI77598 PG 14 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA AU5XP UT WOS:000345677200018 PM 25365221 ER PT J AU Sungalee, S Mamessier, E Morgado, E Gregoire, E Brohawn, PZ Morehouse, CA Jouve, N Monvoisin, C Menard, C Debroas, G Faroudi, M Mechin, V Navarro, JM Drevet, C Eberle, FC Chasson, L Baudimont, F Mancini, SJ Tellier, J Picquenot, JM Kelly, R Vineis, P Ruminy, P Chetaille, B Jaffe, ES Schiff, C Hardwigsen, J Tice, DA Higgs, BW Tarte, K Nadel, B Roulland, S AF Sungalee, Stephanie Mamessier, Emilie Morgado, Ester Gregoire, Emilie Brohawn, Philip Z. Morehouse, Christopher A. Jouve, Nathalie Monvoisin, Celine Menard, Cedric Debroas, Guilhaume Faroudi, Mustapha Mechin, Violaine Navarro, Jean-Marc Drevet, Charlotte Eberle, Franziska C. Chasson, Lionel Baudimont, Fannie Mancini, Stephane J. Tellier, Julie Picquenot, Jean-Michel Kelly, Rachel Vineis, Paolo Ruminy, Philippe Chetaille, Bruno Jaffe, Elaine S. Schiff, Claudine Hardwigsen, Jean Tice, David A. Higgs, Brandon W. Tarte, Karin Nadel, Bertrand Roulland, Sandrine TI Germinal center reentries of BCL2-overexpressing B cells drive follicular lymphoma progression SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Article ID CLASS SWITCH RECOMBINATION; HEALTHY-INDIVIDUALS; T(14/18) TRANSLOCATION; IN-SITU; MEMORY; STEP; TRANSFORMATION; HYPERMUTATION; PATHOGENESIS; ACTIVATION AB It has recently been demonstrated that memory B cells can reenter and reengage germinal center (GC) reactions, opening the possibility that multi-hit lymphomagenesis gradually occurs throughout life during successive immunological challenges. Here, we investigated this scenario in follicular lymphoma (FL), an indolent GC-derived malignancy. We developed a mouse model that recapitulates the FL hallmark t(14;18) translocation, which results in constitutive activation of antiapoptotic protein B cell lymphoma 2 (BCL2) in a subset of B cells, and applied a combination of molecular and immunofluorescence approaches to track normal and t(14;18)(+) memory B cells in human and BCL2-overexpressing B cells in murine lymphoid tissues. BCL2-overexpressing B cells required multiple GC transits before acquiring FL-associated developmental arrest and presenting as GCB cells with constitutive activation-induced cytidine deaminase (AID) mutator activity. Moreover, multiple reentries into the GC were necessary for the progression to advanced precursor stages of FL. Together, our results demonstrate that protracted subversion of immune dynamics contributes to early dissemination and progression of t(14;18)(+) precursors and shapes the systemic presentation of FL patients. C1 [Sungalee, Stephanie; Mamessier, Emilie; Morgado, Ester; Jouve, Nathalie; Debroas, Guilhaume; Faroudi, Mustapha; Mechin, Violaine; Navarro, Jean-Marc; Drevet, Charlotte; Chasson, Lionel; Baudimont, Fannie; Mancini, Stephane J.; Tellier, Julie; Schiff, Claudine; Nadel, Bertrand; Roulland, Sandrine] Aix Marseille Univ, Ctr Immunol Marseille Luminy, F-13288 Marseille 9, France. [Sungalee, Stephanie; Mamessier, Emilie; Morgado, Ester; Jouve, Nathalie; Debroas, Guilhaume; Faroudi, Mustapha; Mechin, Violaine; Navarro, Jean-Marc; Drevet, Charlotte; Chasson, Lionel; Baudimont, Fannie; Mancini, Stephane J.; Tellier, Julie; Schiff, Claudine; Nadel, Bertrand; Roulland, Sandrine] INSERM, U1104, F-13258 Marseille, France. [Sungalee, Stephanie; Mamessier, Emilie; Morgado, Ester; Jouve, Nathalie; Debroas, Guilhaume; Faroudi, Mustapha; Mechin, Violaine; Navarro, Jean-Marc; Drevet, Charlotte; Chasson, Lionel; Baudimont, Fannie; Mancini, Stephane J.; Tellier, Julie; Schiff, Claudine; Nadel, Bertrand; Roulland, Sandrine] CNRS, UMR7280, Marseille, France. [Gregoire, Emilie; Hardwigsen, Jean] Hop Conception, AP HM, Dept Surg & Liver Transplantat, Marseille, France. [Brohawn, Philip Z.; Morehouse, Christopher A.; Tice, David A.; Higgs, Brandon W.] MedImmune, Translat Sci, Gaithersburg, MD USA. [Monvoisin, Celine; Menard, Cedric; Tarte, Karin] Univ Rennes 1, EFS Bretagne, INSERM U917, Rennes, France. [Eberle, Franziska C.; Jaffe, Elaine S.] NCI, Hematopathol Sect, Pathol Lab, Ctr Canc Res, Bethesda, MD 20892 USA. [Picquenot, Jean-Michel; Ruminy, Philippe] Ctr Henri Becquerel, Dept Pathol, INSERM U918, F-76038 Rouen, France. [Kelly, Rachel; Vineis, Paolo] Univ London Imperial Coll Sci Technol & Med, Sch Publ Hlth, MRC HPA Ctr Environm & Hlth, London, England. [Chetaille, Bruno] Inst J Paoli I Calmettes, Dept Pathol, F-13009 Marseille, France. RP Roulland, S (reprint author), Aix Marseille Univ, Ctr Immunol Marseille Luminy, F-13288 Marseille 9, France. EM nadel@ciml.univ-mrs.fr; roulland@ciml.univ-mrs.fr RI Jaffe, Elaine/G-8984-2014; Nadel, Bertrand/J-2197-2014; Mancini, Stephane/R-4109-2016; jouve, nathalie/D-5098-2017; OI Jaffe, Elaine/0000-0003-4632-0301; Mancini, Stephane/0000-0001-9255-4606; Sungalee, Stephanie/0000-0001-5633-8826 FU Institut National du Cancer (INCa); Association pour la Recherche sur le Cancer (ARC); MedImmune Strategic Collaboration to Fund; Conduct Medical Science Research program; INSERM; CNRS; French Ministry of Research (MRT); Fondation pour la Recherche Medicale (FRM) FX This work was funded by grants from the Institut National du Cancer (INCa); the Association pour la Recherche sur le Cancer (ARC); the MedImmune Strategic Collaboration to Fund and Conduct Medical Science Research program; INSERM; and CNRS. S. Sungalee was supported by a fellowship from the French Ministry of Research (MRT) and the Fondation pour la Recherche Medicale (FRM). We thank B. Malissen for providing the LatY136F mice. We thank A. Anginot for help with mice immunization and analysis and R. Fara, A. Camerlot, and D. Novero for providing paired organ donor samples. We thank M. Bajenoff, M. Cogne, and B. Reina-San-Martin for critical reading of the manuscript and C.J. van Noesel for helpful discussions. NR 43 TC 15 Z9 15 U1 1 U2 16 PU AMER SOC CLINICAL INVESTIGATION INC PI ANN ARBOR PA 35 RESEARCH DR, STE 300, ANN ARBOR, MI 48103 USA SN 0021-9738 EI 1558-8238 J9 J CLIN INVEST JI J. Clin. Invest. PD DEC PY 2014 VL 124 IS 12 BP 5337 EP 5351 DI 10.1172/JCI72415 PG 15 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA AU5XP UT WOS:000345677200025 PM 25384217 ER PT J AU Blanch-Hartigan, D Nekhlyudov, L Smith, T Alfano, CM Rowland, JH Forsythe, LP Ganz, PA AF Blanch-Hartigan, Danielle Nekhlyudov, Larissa Smith, Tenbroeck Alfano, Catherine M. Rowland, Julia H. Forsythe, Laura P. Ganz, Patricia A. TI Survivorship Care Plans: A Change of Perspective or a Failure Reply SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Letter ID CANCER SURVIVORS C1 [Blanch-Hartigan, Danielle] Bentley Univ, Waltham, MA 02452 USA. [Nekhlyudov, Larissa] Harvard Univ, Sch Med, Boston, MA 02115 USA. [Nekhlyudov, Larissa] Harvard Vanguard Med Associates, Boston, MA 02115 USA. [Smith, Tenbroeck] Amer Canc Soc, Atlanta, GA 30329 USA. [Alfano, Catherine M.; Rowland, Julia H.] Natl Canc Inst, Bethesda, MD USA. [Forsythe, Laura P.] Patient Centered Outcomes Res Inst, Washington, DC USA. [Ganz, Patricia A.] Univ Calif Los Angeles, Jonsson Comprehens Canc Ctr, Los Angeles, CA 90024 USA. RP Blanch-Hartigan, D (reprint author), Bentley Univ, Waltham, MA 02452 USA. FU PHS HHS [HHSN261200700068C] NR 10 TC 0 Z9 0 U1 0 U2 1 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X EI 1527-7755 J9 J CLIN ONCOL JI J. Clin. Oncol. PD DEC 1 PY 2014 VL 32 IS 34 BP 3905 EP 3906 DI 10.1200/JCO.2014.58.1348 PG 2 WC Oncology SC Oncology GA AU9ID UT WOS:000345904300025 PM 25245438 ER PT J AU Schuster, DM Nanni, C Fanti, S Oka, S Okudaira, H Inoue, Y Sorensen, J Owenius, R Choyke, P Turkbey, B Bogsrud, TV Bach-Gansmo, T Halkar, RK Nye, JA Odewole, OA Savir-Baruch, B Goodman, MM AF Schuster, David M. Nanni, Cristina Fanti, Stefano Oka, Shuntaro Okudaira, Hiroyuki Inoue, Yusuke Sorensen, Jens Owenius, Rikard Choyke, Peter Turkbey, Baris Bogsrud, Trond V. Bach-Gansmo, Tore Halkar, Raghuveer K. Nye, Jonathon A. Odewole, Oluwaseun A. Savir-Baruch, Bital Goodman, Mark M. TI Anti-1-Amino-3-F-18-Fluorocyclobutane-1-Carboxylic Acid: Physiologic Uptake Patterns, Incidental Findings, and Variants That May Simulate Disease SO JOURNAL OF NUCLEAR MEDICINE LA English DT Article DE F-18-FACBC; physiologic uptake; positron emission tomography ID RECURRENT PROSTATE CARCINOMA; RADIOLABELED AMINO-ACIDS; TRANSPORT MECHANISMS; RADIATION-DOSIMETRY; CANCER; PET/CT; BIODISTRIBUTION; RADIOTRACER; AGENT; CELLS AB Anti-1-amino-3-F-18-fluorocyclobutane-1-carboxylic acid (F-18-FACBC) is a synthetic amino acid analog PET radiotracer undergoing clinical trials for the evaluation of prostate and other cancers. We aimed to describe common physiologic uptake patterns, incidental findings, and variants in patients who had undergone F-18-FACBC PET. Methods: Sixteen clinical trials involving 611 F-18-FACBC studies from 6 centers, which included dosimetry studies on 12 healthy volunteers, were reviewed. Qualitative observations of common physiologic patterns, incidental uptake, and variants that could simulate disease were recorded and compared with similar observations in studies of the healthy volunteers. Quantitative analysis of select data and review of prior published reports and observations were also made. Results: The liver and pancreas demonstrated the most intense uptake. Moderate salivary and pituitary uptake and variable mild to moderate bowel activity were commonly visualized. Moderate bone marrow and mild muscle activity were present on early images, with marrow activity decreasing and muscle activity increasing with time. Brain and lungs demonstrated activity less than blood pool. Though F-18-FACBC exhibited little renal excretion or bladder uptake during the clinically useful early imaging time window, mild to moderate activity might accumulate in the bladder and interfere with evaluation of adjacent prostate bed and seminal vesicles in 5%-10% of patients. Uptake might also occur from benign processes such as infection, inflammation, prostatic hyperplasia, and metabolically active benign bone lesions such as osteoid osteoma. Conclusion: Common physiologic uptake patterns were similar to those noted in healthy volunteers. The activity in organs followed the presence of amino acid transport and metabolism described with other amino acid-based PET radiotracers. As with other PET radiotracers such as F-18-FDG, focal nonphysiologic uptake may represent incidental malignancy. Uptake due to benign etiologies distinct from physiologic background also occurred and could lead to misinterpretations if the reader is unaware of them. C1 [Schuster, David M.; Halkar, Raghuveer K.; Nye, Jonathon A.; Odewole, Oluwaseun A.; Savir-Baruch, Bital; Goodman, Mark M.] Emory Univ Hosp, Dept Radiol & Imaging Sci, Atlanta, GA 30322 USA. [Nanni, Cristina; Fanti, Stefano] Univ Bologna, Dept Nucl Med, Policlin S Orsola, Bologna, Italy. [Oka, Shuntaro; Okudaira, Hiroyuki] Nihon Mediphys Co Ltd, Res Ctr, Chiba, Japan. [Inoue, Yusuke] Kitasato Univ, Dept Diagnost Radiol, Sch Med, Kitasato, Japan. [Sorensen, Jens] Uppsala Univ, Dept Radiol Oncol & Radiat Sci, Uppsala, Sweden. [Owenius, Rikard] GE Healthcare, Imaging R&D, Uppsala, Sweden. [Choyke, Peter; Turkbey, Baris] NCI, Mol Imaging Program, Bethesda, MD 20892 USA. [Bogsrud, Trond V.; Bach-Gansmo, Tore] Oslo Univ Hosp, Dept Radiol & Nucl Med, Oslo, Norway. [Bogsrud, Trond V.] Aarhus Univ Hosp, Dept Nucl Med, DK-8000 Aarhus, Denmark. [Bogsrud, Trond V.] Aarhus Univ Hosp, PET Ctr, DK-8000 Aarhus, Denmark. RP Schuster, DM (reprint author), Emory Univ Hosp, Div Nucl Med & Mol Imaging, Dept Radiol & Imaging Sci, Room E152,1364 Clifton Rd, Atlanta, GA 30322 USA. EM dschust@emory.edu RI Schuster, David/D-6156-2011 OI Schuster, David/0000-0003-3077-742X FU National Institutes of Health [5R01CA129356, P50 CA 128301]; Society of Nuclear Medicine and Molecular Imaging Research and Education Foundation; Nihon Medi-Physics Co., Ltd.; GE Healthcare; Blue Earth Diagnostics Limited; Glenn Family Breast Center Award, Winship Cancer Institute of Emory University; Programma di Ricerca Regione (Emilia Romagna)-Universita, Bando Giovani Ricercatori; Georgia Cancer Coalition FX The costs of publication of this article were defrayed in part by the payment of page charges. Therefore, and solely to indicate this fact, this article is hereby marked "advertisement" in accordance with 18 USC section 1734. Support was provided by the National Institutes of Health (5R01CA129356 and P50 CA 128301); Society of Nuclear Medicine and Molecular Imaging Research and Education Foundation; Nihon Medi-Physics Co., Ltd.; GE Healthcare; Blue Earth Diagnostics Limited; Glenn Family Breast Center Award, Winship Cancer Institute of Emory University; Georgia Cancer Coalition; and Programma di Ricerca Regione (Emilia Romagna)-Universita 2010-2012, Bando Giovani Ricercatori. Emory University and Dr. Mark Goodman are eligible to receive royalties for 18F-FACBC. Dr. Schuster participates in sponsored research involving 18F-FACBC and other radiotracers. No other potential conflict of interest relevant to this article was reported. NR 36 TC 11 Z9 11 U1 1 U2 5 PU SOC NUCLEAR MEDICINE INC PI RESTON PA 1850 SAMUEL MORSE DR, RESTON, VA 20190-5316 USA SN 0161-5505 EI 1535-5667 J9 J NUCL MED JI J. Nucl. Med. PD DEC PY 2014 VL 55 IS 12 BP 1986 EP 1992 DI 10.2967/jnumed.114.143628 PG 7 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA AU8EC UT WOS:000345828300015 PM 25453047 ER EF