FN Thomson Reuters Web of Science™ VR 1.0 PT J AU Jayatilaka, HU Kim, SH Chen, JJ Tyle, P Matsuda, M Ju, JA Gilkes, DM Wu, P Lee, JS Fan, R Wirtz, D AF Jayatilaka, H. U. Kim, S. H. Chen, J. J. Tyle, P. Matsuda, M. Ju, J. A. Gilkes, D. M. Wu, P. Lee, J. S. Fan, R. Wirtz, D. TI Functional coupling of cancer cell proliferation and migration through the synergistic paracrine signaling of Interleukins 6/8 SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 [Jayatilaka, H. U.; Kim, S. H.; Tyle, P.; Matsuda, M.; Ju, J. A.; Gilkes, D. M.; Wu, P.; Lee, J. S.; Wirtz, D.] Johns Hopkins Univ, Dept Biomol & Chem Engn, Baltimore, MD USA. [Chen, J. J.; Fan, R.] Yale Univ, Dept Biomed Engn, New Haven, CT USA. [Wu, P.; Wirtz, D.] Johns Hopkins Univ, Johns Hopkins Phys Sci Oncol Ctr, Baltimore, MD USA. [Lee, J. S.] NCI, Ctr Strateg Sci Initiat, Bethesda, MD 20892 USA. [Wirtz, D.] Johns Hopkins Univ, Dept Oncol, Baltimore, MD USA. [Wirtz, D.] Johns Hopkins Univ, Dept Pathol, 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 PY 2015 VL 26 MA P883 PG 1 WC Cell Biology SC Cell Biology GA V47BY UT WOS:000209928500073 ER PT J AU Johnson, DL Wilson, JM Donaldson, J AF Johnson, D. L. Wilson, J. M. Donaldson, J. TI Arf6 and Rab22 control T cell conjugate formation through regulation of the clathrin independent endosomal system SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 [Johnson, D. L.; Donaldson, J.] NHLBI, NIH, Bethesda, MD 20892 USA. [Johnson, D. L.; Wilson, J. M.] Univ Arizona, Cellular & Mol Med, Tucson, AZ USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 EI 1939-4586 J9 MOL BIOL CELL JI Mol. Biol. Cell PY 2015 VL 26 MA P1257 PG 1 WC Cell Biology SC Cell Biology GA V47BY UT WOS:000209928500445 ER PT J AU Katagiri, Y Morgan, AA Yu, P Bangayan, NJ Junka, R Geller, HM AF Katagiri, Y. Morgan, A. A. Yu, P. Bangayan, N. J. Junka, R. Geller, H. M. TI Identification of a Novel Binding Domain for Heparin in RPTPs, but not LAR or RPTP delta: Implications for Proteoglycan Signaling SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 [Katagiri, Y.; Morgan, A. A.; Yu, P.; Bangayan, N. J.; Junka, R.; Geller, H. M.] NHLBI, Dev Neurobiol Sect, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 EI 1939-4586 J9 MOL BIOL CELL JI Mol. Biol. Cell PY 2015 VL 26 MA P604 PG 1 WC Cell Biology SC Cell Biology GA V47BX UT WOS:000209928402213 ER PT J AU Kim, J Staunton, JR Tanner, K AF Kim, J. Staunton, J. R. Tanner, K. TI Independent control of topography and bulk tissue stiffness using magnetic field-induced nanoparticle self-assembly for three-dimensional patterning of the ECM tissue microenvironment SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 [Kim, J.; Staunton, J. R.; Tanner, 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 PY 2015 VL 26 MA P1403 PG 2 WC Cell Biology SC Cell Biology GA V47BY UT WOS:000209928500589 ER PT J AU Kim, K Yang, Y Zhu, J Adelstein, RS Kawamoto, S AF Kim, K. Yang, Y. Zhu, J. Adelstein, R. S. Kawamoto, S. TI Rbfox3 controls the biogenesis of a subset of microRNAs SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 [Kim, K.; Yang, Y.; Zhu, J.; Adelstein, R. S.; Kawamoto, S.] 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 PY 2015 VL 26 MA P1918 PG 1 WC Cell Biology SC Cell Biology GA V47BZ UT WOS:000209928600193 ER PT J AU Konzman, DW Delaspre, F Parsons, MJ Carrington, B Sood, R Gahl, WA Malicdan, MV AF Konzman, D. W. Delaspre, F. Parsons, M. J. Carrington, B. Sood, R. Gahl, W. A. Malicdan, M. V. TI Characterization of zebrafish models of diabetic nephropathy SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 [Konzman, D. W.; Gahl, W. A.; Malicdan, M. V.] NHGRI, Sect Human Biochem Genet, Med Genet Branch, NIH, Bethesda, MD 20892 USA. [Delaspre, F.; Parsons, M. J.] Johns Hopkins Univ, McKusick Nathans Inst Genet Med, Baltimore, MD USA. [Carrington, B.; Sood, R.] NHGRI, Zebrafish Core, Translat & Funct Genom Branch, NIH, Bethesda, MD 20892 USA. [Gahl, W. A.; Malicdan, M. V.] NIH, Undiagnosed Dis Program, Common Fund, Off Director, Bethesda, MD 20892 USA. [Gahl, W. A.; Malicdan, M. V.] NHGRI, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 EI 1939-4586 J9 MOL BIOL CELL JI Mol. Biol. Cell PY 2015 VL 26 MA P780 PG 2 WC Cell Biology SC Cell Biology GA V47BX UT WOS:000209928402388 ER PT J AU Kraft, ML Klitzing, HA Kim, R Weber, PK Zimmerberg, J AF Kraft, M. L. Klitzing, H. A. Kim, R. Weber, P. K. Zimmerberg, J. TI Interplay between Membrane Traffic and Sphingolipid Organization in the Plasma Membrane. SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 [Kraft, M. L.; Klitzing, H. A.; Kim, R.] Univ Illinois, Sch Chem Sci, Urbana, IL 61801 USA. [Weber, P. K.] Lawrence Livermore Natl Lab, Chem Biol & Nucl Sci, Livermore, CA USA. [Zimmerberg, J.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, NIH, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 EI 1939-4586 J9 MOL BIOL CELL JI Mol. Biol. Cell PY 2015 VL 26 MA M70 PG 1 WC Cell Biology SC Cell Biology GA V47BX UT WOS:000209928400166 ER PT J AU Kruhlak, MJ Khurana, S Burgess, R Nyswaner, K Shi, L Ofir, H Burman, B Misteli, T Nussenzweig, A Oberdoerffer, P AF Kruhlak, M. J. Khurana, S. Burgess, R. Nyswaner, K. Shi, L. Ofir, H. Burman, B. Misteli, T. Nussenzweig, A. Oberdoerffer, P. TI Dynamic Chromatin Structural Changes are involved in the Activation of DNA Damage Response Signaling and Promoting BRCA1-Dependent Genome Maintenance SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 [Kruhlak, M. J.] NCI, Expt Immunol Branch, Bethesda, MD 20892 USA. [Khurana, S.; Burgess, R.; Burman, B.; Misteli, T.; Oberdoerffer, P.] NCI, Cell Biol Genomes Grp, Bethesda, MD 20892 USA. [Burgess, R.] Stevenson Univ, Stevenson, MD USA. [Nyswaner, K.; Shi, L.; Ofir, H.] NCI, Frederick Natl Lab, Frederick, MD 21701 USA. [Burman, B.] Tufts Univ, Sackler Sch Biomed Sci, Boston, MA 02111 USA. [Nussenzweig, A.] NCI, Lab Genom Integr, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 EI 1939-4586 J9 MOL BIOL CELL JI Mol. Biol. Cell PY 2015 VL 26 MA P1160 PG 2 WC Cell Biology SC Cell Biology GA V47BY UT WOS:000209928500348 ER PT J AU Lerit, DA Jordan, HA Poulton, JS Fagerstrom, CJ Brian, GJ Peifer, M Rusan, NM AF Lerit, D. A. Jordan, H. A. Poulton, J. S. Fagerstrom, C. J. Brian, G. J. Peifer, M. Rusan, N. M. TI Proper organization of the interphase centrosome structure through the coordinated activities of Centrosomin and Pericentrin-like protein is essential for viability SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 [Lerit, D. A.; Jordan, H. A.; Fagerstrom, C. J.; Brian, G. J.; Rusan, N. M.] NHLBI, Cell Biol & Physiol Ctr, NIH, Bldg 10, Bethesda, MD 20892 USA. [Poulton, J. S.; Peifer, M.] Univ North Carolina Chapel Hill, Biol Dept, Chapel Hill, NC USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 EI 1939-4586 J9 MOL BIOL CELL JI Mol. Biol. Cell PY 2015 VL 26 MA P232 PG 2 WC Cell Biology SC Cell Biology GA V47BX UT WOS:000209928401259 ER PT J AU Lerit, DA Jordan, HA Poulton, JS Fagerstrom, CJ Brian, GJ Peifer, M Rusan, NM AF Lerit, D. A. Jordan, H. A. Poulton, J. S. Fagerstrom, C. J. Brian, G. J. Peifer, M. Rusan, N. M. TI Proper organization of the interphase centrosome structure through the coordinated activities of Centrosomin and Pericentrin-like protein is essential for viability. SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 [Lerit, D. A.; Jordan, H. A.; Fagerstrom, C. J.; Brian, G. J.; Rusan, N. M.] NHLBI, Cell Biol & Physiol Ctr, NIH, Bethesda, MD 20892 USA. [Poulton, J. S.; Peifer, M.] Univ North Carolina Chapel Hill, 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 PY 2015 VL 26 MA M60 PG 2 WC Cell Biology SC Cell Biology GA V47BX UT WOS:000209928400156 ER PT J AU Li, C Le, K Moss, J Vaughan, M AF Li, C. Le, K. Moss, J. Vaughan, M. TI Regulation of beta-catenin activity by Arf guanine nucleotide-exchange factors BIG1 and BIG2 via direct interaction SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 [Li, C.; Le, K.; Moss, J.; Vaughan, M.] NHLBI, Cardiovasc & Pulm Branch, NIH, Bethesda, MD 20892 USA. [Li, C.] Natl Cheng Kung Univ, Dept Life Sci, Tainan, Taiwan. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 EI 1939-4586 J9 MOL BIOL CELL JI Mol. Biol. Cell PY 2015 VL 26 MA P2001 PG 2 WC Cell Biology SC Cell Biology GA V47BZ UT WOS:000209928600275 ER PT J AU Logue, JS Cartagena-Rivera, AX Baird, MA Davidson, MW Chadwick, RS Waterman, CM AF Logue, J. S. Cartagena-Rivera, A. X. Baird, M. A. Davidson, M. W. Chadwick, R. S. Waterman, C. M. TI Erk regulation of actin capping and bundling by Eps8 promotes cortex tension and leader bleb-based migration SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 [Logue, J. S.; Waterman, C. M.] NHLBI, NIH, Bethesda, MD 20892 USA. [Logue, J. S.; Cartagena-Rivera, A. X.; Chadwick, R. S.] NIDCD, NIH, Bethesda, MD USA. [Baird, M. A.; Davidson, M. W.] Florida State Univ, Natl High Magnet Field Lab, Tallahassee, FL 32306 USA. [Baird, M. A.; Davidson, M. W.] Florida State Univ, Dept Biol Sci, Tallahassee, FL 32306 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 EI 1939-4586 J9 MOL BIOL CELL JI Mol. Biol. Cell PY 2015 VL 26 MA P249 PG 1 WC Cell Biology SC Cell Biology GA V47BX UT WOS:000209928401276 ER PT J AU Ma, X Adelstein, RS AF Ma, X. Adelstein, R. S. TI Normal Heart Development Requires Epicardial Expression of Nonmuscle Myosin II-B. SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 [Ma, X.; Adelstein, R. S.] NHLBI, Mol Cardiol 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 PY 2015 VL 26 MA P676 PG 1 WC Cell Biology SC Cell Biology GA V47BX UT WOS:000209928402285 ER PT J AU Mactaggart, B Bowen, C Chong, JX Bamshad, MJ Ma, X Adelstein, RS AF Mactaggart, B. Bowen, C. Chong, J. X. Bamshad, M. J. Ma, X. Adelstein, R. S. TI Using Whole Exomic Sequencing to Identify Genetic Variants in Patients Diagnosed with Pentalogy of Cantrell SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 [Mactaggart, B.; Bowen, C.; Ma, X.; Adelstein, R. S.] NHLBI, Mol Cardiol Lab, NIH, Bethesda, MD 20892 USA. [Chong, J. X.; Bamshad, M. J.] Univ Washington, Ctr Mendelian Genom, Seattle, WA 98195 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 EI 1939-4586 J9 MOL BIOL CELL JI Mol. Biol. Cell PY 2015 VL 26 MA P2318 PG 1 WC Cell Biology SC Cell Biology GA V47BZ UT WOS:000209928600582 ER PT J AU Malide, D AF Malide, D. TI Imaging adipose tissue across scales: from two-photon to super-resolution microscopy SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract 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 PY 2015 VL 26 MA P782 PG 2 WC Cell Biology SC Cell Biology GA V47BX UT WOS:000209928402389 ER PT J AU Markossian, S Arnaoutov, A Saba, NS Larionov, V Dasso, M AF Markossian, S. Arnaoutov, A. Saba, N. S. Larionov, V. Dasso, M. TI Quantitative Assessment of Chromosome Instability Induced through chemical disruption of mitotic progression. SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 [Markossian, S.; Arnaoutov, A.; Dasso, M.] NICHHD, Lab Gene Regulat & Dev, Bethesda, MD 20892 USA. [Saba, N. S.] Tulane Univ, Dept Med, Sect Hematol & Med Oncol, New Orleans, LA 70118 USA. [Larionov, V.] NCI, Dev Therapeut Branch, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 EI 1939-4586 J9 MOL BIOL CELL JI Mol. Biol. Cell PY 2015 VL 26 MA P190 PG 1 WC Cell Biology SC Cell Biology GA V47BX UT WOS:000209928401218 ER PT J AU Markossian, S Arnaoutov, A Saba, NS Larionov, V Dasso, M AF Markossian, S. Arnaoutov, A. Saba, N. S. Larionov, V. Dasso, M. TI Quantitative Assessment of Chromosome Instability Induced through chemical disruption of mitotic progression. SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 [Markossian, S.; Arnaoutov, A.; Dasso, M.] NICHHD, Lab Gene Regulat & Dev, Bethesda, MD 20892 USA. [Saba, N. S.] Tulane Univ, Dept Med, Sect Hematol & Med Oncol, New Orleans, LA 70118 USA. [Larionov, V.] NCI, Dev Therapeut Branch, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 EI 1939-4586 J9 MOL BIOL CELL JI Mol. Biol. Cell PY 2015 VL 26 MA M18 PG 1 WC Cell Biology SC Cell Biology GA V47BX UT WOS:000209928400065 ER PT J AU Martin, MM Redmond, C Smith, OK Fu, H Zhang, Y Ryan, M Kim, R Epner, EM Mirit, AI AF Martin, M. M. Redmond, C. Smith, O. K. Fu, H. Zhang, Y. Ryan, M. Kim, R. Epner, E. M. Mirit, A. I. TI CDK independent role of chromatin-bound nuclear cyclin D1 in cancer SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 [Martin, M. M.] Grambling State Univ, Grambling, LA USA. [Redmond, C.] Univ Maryland Baltimore Cty, Baltimore, MD 21228 USA. [Smith, O. K.; Fu, H.; Zhang, Y.; Mirit, A. I.] NCI, Dev Therapeut Branch, NIH, Bethesda, MD 20892 USA. [Ryan, M.] In Silico Solut, Falls Church, VA USA. [Epner, E. M.] Penn State Univ, Hershey, PA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 EI 1939-4586 J9 MOL BIOL CELL JI Mol. Biol. Cell PY 2015 VL 26 MA P296 PG 2 WC Cell Biology SC Cell Biology GA V47BX UT WOS:000209928401323 ER PT J AU Martina, JA Diab, HI Brady, OA Puertollano, R AF Martina, J. A. Diab, H. I. Brady, O. A. Puertollano, R. TI Novel role of TFEB and TFE3 in cellular response to ER stress SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 [Martina, J. A.; Diab, H. I.; Brady, O. A.; Puertollano, R.] 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 PY 2015 VL 26 MA P2003 PG 2 WC Cell Biology SC Cell Biology GA V47BZ UT WOS:000209928600277 ER PT J AU Mehedi, M McCarty, T Martin, S Nouen, C Buehler, E Chen, Y Smelkinson, M Ganesan, S Fischer, E Brock, L Liang, B Hoenen, T Munir, S Collins, P Buchholz, U AF Mehedi, M. McCarty, T. Martin, S. Nouen, C. Buehler, E. Chen, Y. Smelkinson, M. Ganesan, S. Fischer, E. Brock, L. Liang, B. Hoenen, T. Munir, S. Collins, P. Buchholz, U. TI Actin-related protein 2 (ARP2) and filopodia promote human respiratory syncytial virus spread in respiratory epithelial cells SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 [Mehedi, M.; McCarty, T.; Nouen, C.; Brock, L.; Liang, B.; Munir, S.; Collins, P.; Buchholz, U.] NIAID, Infect Dis Lab, NIH, Bethesda, MD 20892 USA. [Martin, S.; Buehler, E.; Chen, Y.] NIH, Div Preclin Innovat, NCATS, Rockville, MD USA. [Smelkinson, M.; Ganesan, S.] NIAID, Biol Imaging Sect, RTB, NIH, Bethesda, MD 20892 USA. [Fischer, E.] NIH, Electron Microscopy Unit, Rocky Mt Labs, Hamilton, MT USA. [Hoenen, T.] NIH, Lab Virol, Rocky Mt Labs, Hamilton, MT USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 EI 1939-4586 J9 MOL BIOL CELL JI Mol. Biol. Cell PY 2015 VL 26 MA P758 PG 2 WC Cell Biology SC Cell Biology GA V47BX UT WOS:000209928402366 ER PT J AU Mehta, SB Fischer, RS Spira, FG Gerlich, DW Waterman, CM Oldenbourg, R AF Mehta, S. B. Fischer, R. S. Spira, F. G. Gerlich, D. W. Waterman, C. M. Oldenbourg, R. TI Three dimensional imaging of molecular order of the cytoskeleton by confocal fluorescence polarization microscopy SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 [Mehta, S. B.; Oldenbourg, R.] Marine Biol Lab, Eugene Bell Ctr Regenerat Biol Tissue Engn, Woods Hole, MA 02543 USA. [Fischer, R. S.; Waterman, C. M.] NHLBI, Cell Biol & Physiol Ctr, Bethesda, MD 20892 USA. [Spira, F. G.; Gerlich, D. W.] Austrian Acad Sci, Inst Mol Biotechnol, Vienna, Austria. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 EI 1939-4586 J9 MOL BIOL CELL JI Mol. Biol. Cell PY 2015 VL 26 MA P1625 PG 2 WC Cell Biology SC Cell Biology GA V47BY UT WOS:000209928500819 ER PT J AU Meinhardt, JT Madison, G Hong, J Murugesan, S Hammer, JA AF Meinhardt, J. T. Madison, G. Hong, J. Murugesan, S. Hammer, J. A. TI Determining the role of formins mDia1 and FMNL1 in actin arc formation at the Jurkat T cell immune synapse SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 [Meinhardt, J. T.; Madison, G.; Hong, J.; Murugesan, S.; Hammer, J. A.] NHLBI, NIH, Bethesda, MD 20892 USA. [Meinhardt, J. T.] Hampden Sydney Coll, Biol, Hampden Sydney, VA 23943 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 EI 1939-4586 J9 MOL BIOL CELL JI Mol. Biol. Cell PY 2015 VL 26 MA P63 PG 1 WC Cell Biology SC Cell Biology GA V47BX UT WOS:000209928401090 ER PT J AU Meseroll, RA Cohen-Fix, O AF Meseroll, R. A. Cohen-Fix, O. TI The essential DNA topoisomerase, Top2, is required for normal nuclear morphology SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 [Meseroll, R. A.; Cohen-Fix, O.] Natl Inst Diabet & Digest & Kidney Dis, NIH, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 EI 1939-4586 J9 MOL BIOL CELL JI Mol. Biol. Cell PY 2015 VL 26 MA P1194 PG 2 WC Cell Biology SC Cell Biology GA V47BY UT WOS:000209928500382 ER PT J AU Moore, TI Nordenfelt, P Mehta, S Lambert, T Swaminathan, V Mathew, JK Koga, N Baker, D Tani, T Mayor, S Waterman, CM Springer, TA AF Moore, T. I. Nordenfelt, P. Mehta, S. Lambert, T. Swaminathan, V. Mathew, J. K. Koga, N. Baker, D. Tani, T. Mayor, S. Waterman, C. M. Springer, T. A. TI Leukocyte integrin LFA-1 is aligned and oriented by actin flow during cell migration. SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 [Moore, T. I.; Nordenfelt, P.; Springer, T. A.] Boston Childrens Hosp, Program Cellular & Mol Med, Boston, MA USA. [Moore, T. I.; Nordenfelt, P.; Springer, T. A.] Harvard Med Sch, Biol Chem & Mol Pharmacol, Boston, MA USA. [Moore, T. I.; Nordenfelt, P.; Swaminathan, V.; Mathew, J. K.; Mayor, S.; Waterman, C. M.; Springer, T. A.] Marine Biol Lab, Whitman Ctr, Woods Hole, MA 02543 USA. [Nordenfelt, P.; Swaminathan, V.; Mathew, J. K.; Mayor, S.; Waterman, C. M.] Marine Biol Lab, Physiol Course, Woods Hole, MA 02543 USA. [Mehta, S.; Tani, T.] Marine Biol Lab, Eugene Bell Ctr, Woods Hole, MA 02543 USA. [Lambert, T.] Harvard Med Sch, Nikon Imaging Ctr, Boston, MA USA. [Swaminathan, V.; Waterman, C. M.] NHLBI, Cell Biol & Physiol Ctr, NIH, Bethesda, MD 20892 USA. [Mathew, J. K.; Mayor, S.] Natl Ctr Biol Sci, TIFR, Bangalore, Karnataka, India. [Koga, N.; Baker, D.] Univ Washington, Biochem, Seattle, WA 98195 USA. [Baker, D.] Howard Hughes Med Inst, Seattle, WA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 EI 1939-4586 J9 MOL BIOL CELL JI Mol. Biol. Cell PY 2015 VL 26 MA E6 PG 2 WC Cell Biology SC Cell Biology GA V47BX UT WOS:000209928400012 ER PT J AU Moore, TI Nordenfelt, P Mehta, S Lambert, T Swaminathan, V Mathew, JK Koga, N Baker, D Tani, T Mayor, S Waterman, CM Springer, TA AF Moore, T. I. Nordenfelt, P. Mehta, S. Lambert, T. Swaminathan, V. Mathew, J. K. Koga, N. Baker, D. Tani, T. Mayor, S. Waterman, C. M. Springer, T. A. TI Leukocyte integrin LFA-1 is aligned and oriented by actin flow during cell migration SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 [Moore, T. I.; Nordenfelt, P.; Springer, T. A.] Boston Childrens Hosp, Program Cellular & Mol Med, Boston, MA USA. [Moore, T. I.; Nordenfelt, P.; Springer, T. A.] Harvard Med Sch, Biol Chem & Mol Pharmacol, Boston, MA USA. [Moore, T. I.; Nordenfelt, P.; Swaminathan, V.; Mathew, J. K.; Mayor, S.; Waterman, C. M.; Springer, T. A.] Marine Biol Lab, Whitman Ctr, Woods Hole, MA 02543 USA. [Nordenfelt, P.; Swaminathan, V.; Mathew, J. K.; Mayor, S.; Waterman, C. M.] Marine Biol Lab, Physiol Course, Woods Hole, MA 02543 USA. [Mehta, S.; Tani, T.] Marine Biol Lab, Eugene Bell Ctr, Woods Hole, MA 02543 USA. [Lambert, T.] Harvard Med Sch, Nikon Imaging Ctr, Boston, MA USA. [Swaminathan, V.; Waterman, C. M.] NHLBI, Cell Biol & Physiol Ctr, NIH, Bethesda, MD 20892 USA. [Mathew, J. K.; Mayor, S.] Natl Ctr Biol Sci, TIFR, Bangalore, Karnataka, India. [Koga, N.; Baker, D.] Univ Washington, Biochem, Seattle, WA 98195 USA. [Koga, N.; Baker, D.] Howard Hughes Med Inst, Seattle, WA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 EI 1939-4586 J9 MOL BIOL CELL JI Mol. Biol. Cell PY 2015 VL 26 MA P2153 PG 2 WC Cell Biology SC Cell Biology GA V47BZ UT WOS:000209928600427 ER PT J AU Murugesan, S Hong, J Yi, J Li, D Shao, L Wu, X Betzig, E Hammer, JA AF Murugesan, S. Hong, J. Yi, J. Li, D. Shao, L. Wu, X. Betzig, E. Hammer, J. A. TI Formin-generated actin arcs and myosin II cooperate to create a contractile structure that drives the maturation of the immune synapse SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 [Murugesan, S.; Hong, J.; Yi, J.; Wu, X.; Hammer, J. A.] NIH, Cell Biol & Physiol Ctr, Bethesda, MD 20892 USA. [Li, D.; Shao, L.; Betzig, E.] Janelia Farm Res Campus, 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 PY 2015 VL 26 MA P62 PG 1 WC Cell Biology SC Cell Biology GA V47BX UT WOS:000209928401089 ER PT J AU Nixon-Abell, J Obara, CJ Weigel, AV Li, D Legant, WR Harvey, K Betzig, E Lippincott-Schwartz, J Blackstone, CD AF Nixon-Abell, J. Obara, C. J. Weigel, A. V. Li, D. Legant, W. R. Harvey, K. Betzig, E. Lippincott-Schwartz, J. Blackstone, C. D. TI Increased spatiotemporal resolution reveals highly dynamic, tubular lattices in the peripheral endoplasmic reticulum. SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 [Nixon-Abell, J.; Blackstone, C. D.] NINDS, Cell Neurol Sect, Bethesda, MD 20892 USA. [Nixon-Abell, J.; Harvey, K.] UCL Sch Pharm, Dept Pharmacol, London, England. [Obara, C. J.; Weigel, A. V.; Lippincott-Schwartz, J.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Sect Organelle Biol, Bethesda, MD USA. [Li, D.; Legant, W. R.; Betzig, E.] Howard Hughes Med Inst, Janelia Res Campus, Ashburn, VA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 EI 1939-4586 J9 MOL BIOL CELL JI Mol. Biol. Cell PY 2015 VL 26 MA M169 PG 2 WC Cell Biology SC Cell Biology GA V47BX UT WOS:000209928400324 ER PT J AU Nixon-Abell, J Obara, CJ Weigel, AV Li, D Legant, WR Harvey, K Betzig, E Lippincott-Schwartz, J Blackstone, CD AF Nixon-Abell, J. Obara, C. J. Weigel, A. V. Li, D. Legant, W. R. Harvey, K. Betzig, E. Lippincott-Schwartz, J. Blackstone, C. D. TI Increased spatiotemporal resolution reveals highly dynamic, tubular lattices in the peripheral endoplasmic reticulum SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 [Nixon-Abell, J.; Harvey, K.] UCL Sch Pharm, Dept Pharmacol, London, England. [Nixon-Abell, J.; Blackstone, C. D.] NINDS, Cell Neurol Sect, Bethesda, MD 20892 USA. [Obara, C. J.; Weigel, A. V.; Lippincott-Schwartz, J.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Sect Organelle Biol, Bethesda, MD USA. [Li, D.; Legant, W. R.; Betzig, E.] Howard Hughes Med Inst, Ashburn, VA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 EI 1939-4586 J9 MOL BIOL CELL JI Mol. Biol. Cell PY 2015 VL 26 MA P1299 PG 1 WC Cell Biology SC Cell Biology GA V47BY UT WOS:000209928500485 ER PT J AU Ott, CM Nachmias, D Jarnik, M Lippincott-Schwartz, J Elia, N AF Ott, C. M. Nachmias, D. Jarnik, M. Lippincott-Schwartz, J. Elia, N. TI The AAATPase VPS4 shapes early steps in cilia formation and alters centriolar satellites and the pericentriolar material SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 [Ott, C. M.; Jarnik, M.; Lippincott-Schwartz, J.] NICHHD, Cell Biol, Bethesda, MD 20892 USA. [Nachmias, D.; Elia, N.] Ben Gurion Univ Negev, Dept Life Sci, Beer Sheva, Israel. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 EI 1939-4586 J9 MOL BIOL CELL JI Mol. Biol. Cell PY 2015 VL 26 MA P1757 PG 1 WC Cell Biology SC Cell Biology GA V47BZ UT WOS:000209928600032 ER PT J AU Park, J Kim, T Meng, L Lee, KS AF Park, J. Kim, T. Meng, L. Lee, K. S. TI Selective blockade of cancer cell proliferation and anchorage-independent growth by Plk1 activity-dependent suicidal inhibition of its polo-box domain SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 [Park, J.; Kim, T.; Meng, L.; Lee, K. S.] NCI, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 EI 1939-4586 J9 MOL BIOL CELL JI Mol. Biol. Cell PY 2015 VL 26 MA P1897 PG 1 WC Cell Biology SC Cell Biology GA V47BZ UT WOS:000209928600172 ER PT J AU Pasapera-Limon, AM Fischer, RS Waterman, CM AF Pasapera-Limon, A. M. Fischer, R. S. Waterman, C. M. TI Microtubule affinity-regulating kinase2 is associated with Actin and Focal adhesions to regulate directed cell migration SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 [Pasapera-Limon, A. M.; Fischer, R. S.; Waterman, C. M.] NIH, Cell Biol & Physiol Ctr, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 EI 1939-4586 J9 MOL BIOL CELL JI Mol. Biol. Cell PY 2015 VL 26 MA P582 PG 1 WC Cell Biology SC Cell Biology GA V47BX UT WOS:000209928402191 ER PT J AU Petrie, RJ Yamada, KM AF Petrie, R. J. Yamada, K. M. TI Activating the nuclear piston mechanism to generate intracellular pressure during 3D cancer cell migration. SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 [Petrie, R. J.] Drexel Univ, Biol, Philadelphia, PA 19104 USA. [Yamada, K. M.] NIDCR, NIH, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 EI 1939-4586 J9 MOL BIOL CELL JI Mol. Biol. Cell PY 2015 VL 26 MA P2248 PG 1 WC Cell Biology SC Cell Biology GA V47BZ UT WOS:000209928600513 ER PT J AU Petrie, TA Jug, F Schwartz, JL AF Petrie, T. A. Jug, F. Schwartz, J. Lippincott TI M1 and M2 polarized fused "hybrid" cells display distinct fusion mechanics and bioenergetics SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 [Petrie, T. A.; Schwartz, J. Lippincott] NICHD, NIH, Bethesda, MD USA. [Petrie, T. A.; Jug, F.; Schwartz, J. Lippincott] Marine Biol Lab, Physiol Course, Woods Hole, MA 02543 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 EI 1939-4586 J9 MOL BIOL CELL JI Mol. Biol. Cell PY 2015 VL 26 MA P580 PG 2 WC Cell Biology SC Cell Biology GA V47BX UT WOS:000209928402189 ER PT J AU Pickrell, AM Kennedy, SR Huang, C Ordureau, A Sideris, DP Hoekstra, J Harper, JW Youle, RJ AF Pickrell, A. M. Kennedy, S. R. Huang, C. Ordureau, A. Sideris, D. P. Hoekstra, J. Harper, J. W. Youle, R. J. TI Endogenous Parkin Preserves Dopaminergic Substantia Nigral Neurons following Mitochondrial DNA Mutagenic Stress. SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 [Pickrell, A. M.; Huang, C.; Sideris, D. P.; Youle, R. J.] NINDS, NIH, Bethesda, MD 20892 USA. [Kennedy, S. R.; Hoekstra, J.] Univ Washington, Dept Pathol, Seattle, WA 98195 USA. [Ordureau, A.; Harper, J. W.] Harvard Med Sch, Dept Cell Biol, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 EI 1939-4586 J9 MOL BIOL CELL JI Mol. Biol. Cell PY 2015 VL 26 MA M214 PG 1 WC Cell Biology SC Cell Biology GA V47BX UT WOS:000209928401010 ER PT J AU Pim, D Broniarczyk, J Bergant, M Playford, M Banks, L AF Pim, D. Broniarczyk, J. Bergant, M. Playford, M. Banks, L. TI Exploitation of host cell endosomal pathways by papillomavirus L2 protein during viral trafficking to the nucleus - involvement of sorting nexins 17 and 27. SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 [Pim, D.; Banks, L.] Int Ctr Genet Engn & Biotechnol, Tumour Virol, Trieste, Italy. [Broniarczyk, J.] Adam Mickiewicz Univ, Dept Mol Virol, Poznzn, Poland. [Bergant, M.] Univ Nova Gorica, Ctr Biomed Sci & Engn, Nova Gorica, Slovenia. [Playford, M.] 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 PY 2015 VL 26 MA P466 PG 1 WC Cell Biology SC Cell Biology GA V47BX UT WOS:000209928402076 ER PT J AU Porat-Shliom, N Harding, O Chen, Y Weigert, R AF Porat-Shliom, N. Harding, O. Chen, Y. Weigert, R. TI Stimulation of Regulated Exocytosis Induces Changes in Mitochondrial Organization and Metabolism to Sustain Membrane Remodeling in Live Animals. SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 [Porat-Shliom, N.; Harding, O.; Chen, Y.; Weigert, R.] NCI, Cellular & Mol Biol Lab, 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 PY 2015 VL 26 MA P452 PG 2 WC Cell Biology SC Cell Biology GA V47BX UT WOS:000209928402063 ER PT J AU Pronobis, M Peifer, M Rusan, NM AF Pronobis, M. Peifer, M. Rusan, N. M. TI A novel GSK3-regulated APC: Axin interaction regulates Wnt signaling by driving a catalytic cycle of efficient beta catenin destruction. SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 [Pronobis, M.; Peifer, M.] Univ North Carolina Chapel Hill, Curriculum Genet & Mol Biol, Chape Hill, NC USA. [Peifer, M.] Univ North Carolina Chapel Hill, Biol, Chapel Hill, NC USA. [Rusan, N. M.] 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 PY 2015 VL 26 MA P520 PG 2 WC Cell Biology SC Cell Biology GA V47BX UT WOS:000209928402130 ER PT J AU Pronobis, M Peifer, M Rusan, NM AF Pronobis, M. Peifer, M. Rusan, N. M. TI A novel GSK3-regulated APC: Axin interaction regulates Wnt signaling by driving a catalytic cycle of efficient beta catenin destruction. SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 [Pronobis, M.; Peifer, M.] Univ North Carolina Chapel Hill, Curriculum Genet & Mol Biol, Chape Hill, NC USA. [Peifer, M.] Univ North Carolina Chapel Hill, Biol, Chapel Hill, NC USA. [Rusan, N. M.] 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 PY 2015 VL 26 MA E83 PG 1 WC Cell Biology SC Cell Biology GA V47BX UT WOS:000209928400154 ER PT J AU Quintanilla, I Wangsa, D Brown, M Vila, M Ercilla, A Lozano, J Agell, N Castells, A Szallasi, Z Cimini, D Ried, T Camps, J AF Quintanilla, I. Wangsa, D. Brown, M. Vila, M. Ercilla, A. Lozano, J. Agell, N. Castells, A. Szallasi, Z. Cimini, D. Ried, T. Camps, J. TI Replication stress and DNA damage promote genomic instability in near-tetraploid cancer cells SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 [Quintanilla, I.; Castells, A.; Camps, J.] Inst Invest Biomed August Pi & Sunyer, Gastrointestinal, Barcelona, Spain. [Wangsa, D.; Brown, M.; Ried, T.] NCI, Genet Branch, NIH, Bethesda, MD 20892 USA. [Vila, M.; Lozano, J.] CIBERehd, Bioinformat, Barcelona, Spain. [Ercilla, A.; Agell, N.] Univ Barcelona, Biol Celular & Neurociencies, Barcelona, Spain. [Szallasi, Z.] Harvard Med Sch, Boston, MA USA. [Cimini, D.] Virginia Tech, Biol Sci, Bioinformat Inst, Blacksburg, VA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 EI 1939-4586 J9 MOL BIOL CELL JI Mol. Biol. Cell PY 2015 VL 26 MA P1884 PG 1 WC Cell Biology SC Cell Biology GA V47BZ UT WOS:000209928600159 ER PT J AU Ramos, CI Serpe, M AF Ramos, C. I. Serpe, M. TI Neto-mediated intracellular interactions organize postsynaptic structures at the Drosophila neuromuscular junction SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 [Ramos, C. I.; Serpe, 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 PY 2015 VL 26 MA P2041 PG 2 WC Cell Biology SC Cell Biology GA V47BZ UT WOS:000209928600315 ER PT J AU Randazzo, D Oddoux, S Zaal, KJ Talsness, DM Belanto, JJ Tran, MD Kenea, A Ervasti, JM Ralston, E AF Randazzo, D. Oddoux, S. Zaal, K. J. Talsness, D. M. Belanto, J. J. Tran, M. D. Kenea, A. Ervasti, J. M. Ralston, E. TI Changes in the balance of specific tubulin isotypes perturb the organization of skeletal muscle microtubules SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 [Randazzo, D.; Oddoux, S.; Zaal, K. J.; Tran, M. D.; Kenea, A.; Ralston, E.] NIAMSD, Light Imaging Sect, Off Sci & Technol, NIH, Bethesda, MD 20892 USA. [Talsness, D. M.; Belanto, J. J.; Ervasti, J. M.] Univ Minnesota Twin Cities, Dept Biochem Mol Biol & Biophys, Program Mol Cellular Dev Biol & Genet, Minneapolis, MN USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 EI 1939-4586 J9 MOL BIOL CELL JI Mol. Biol. Cell PY 2015 VL 26 MA P952 PG 2 WC Cell Biology SC Cell Biology GA V47BY UT WOS:000209928500141 ER PT J AU Raval, MH Quintero, OA Weck, ML Unrath, W Gallagher, J Runjia, C Kachar, B Tyska, MJ Yengo, CM AF Raval, M. H. Quintero, O. A. Weck, M. L. Unrath, W. Gallagher, J. Runjia, C. Kachar, B. Tyska, M. J. Yengo, C. M. TI MECHANISM OF CLASS III MYOSIN-INDUCED ACTIN PROTRUSION FORMATION AND ELONGATION SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 [Raval, M. H.; Unrath, W.; Yengo, C. M.] Penn State Univ, Dept Cellular & Mol Physiol, Coll Med, Hershey, PA USA. [Quintero, O. A.] Univ Richmond, Dept Biol, Richmond, VA 23173 USA. [Weck, M. L.; Tyska, M. J.] Vanderbilt Univ, Med Ctr, Dept Cell & Dev Biol, Nashville, TN USA. [Gallagher, J.] Lincoln Univ, Dept Biol, Philadelphia, PA USA. [Runjia, C.; Kachar, B.] Natl Inst Deafness & Other Commun Disorders, NIH, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 EI 1939-4586 J9 MOL BIOL CELL JI Mol. Biol. Cell PY 2015 VL 26 MA P1712 PG 1 WC Cell Biology SC Cell Biology GA V47BY UT WOS:000209928500906 ER PT J AU Ricca, BL Venugopalan, G Tanner, K Furata, S Orellana, WA Reber, CD Brownfield, D Bissell, MJ Fletcher, DA AF Ricca, B. L. Venugopalan, G. Tanner, K. Furata, S. Orellana, W. A. Reber, C. D. Brownfield, D. Bissell, M. J. Fletcher, D. A. TI Transient Nitric Oxide Signal Drives Mechanically-Induced Phenotypic Reversion SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 [Ricca, B. L.; Venugopalan, G.; Reber, C. D.; Brownfield, D.; Fletcher, D. A.] Univ Calif Berkeley, Bioengn Dept, Biophys Program, Berkeley, CA 94720 USA. [Tanner, K.; Orellana, W. A.] NCI, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. [Tanner, K.; Furata, S.; Orellana, W. A.; Brownfield, D.; Bissell, M. J.] Lawrence Berkeley Natl Lab, Div Life Sci, Berkeley, CA USA. [Fletcher, D. A.] Lawrence Berkeley Natl Lab, Phys Biosci Div, Berkeley, CA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 EI 1939-4586 J9 MOL BIOL CELL JI Mol. Biol. Cell PY 2015 VL 26 MA P1878 PG 1 WC Cell Biology SC Cell Biology GA V47BZ UT WOS:000209928600153 ER PT J AU Ritter, AT Griffiths, GM Lippincott-Schwartz, J AF Ritter, A. T. 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 C1 [Ritter, A. T.; Lippincott-Schwartz, J.] NICHD, NIH, Bethesda, MD USA. [Ritter, A. T.; Griffiths, G. M.] Univ Cambridge, Cambridge Inst Med Res, Cambridge, England. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 EI 1939-4586 J9 MOL BIOL CELL JI Mol. Biol. Cell PY 2015 VL 26 MA P370 PG 2 WC Cell Biology SC Cell Biology GA V47BX UT WOS:000209928401397 ER PT J AU Rutledge, SD Douglas, TA Kantzler, CL Wangsa, D Kale, SD Logarinho, E Cimini, D AF Rutledge, S. D. Douglas, T. A. Kantzler, C. L. Wangsa, D. Kale, S. D. Logarinho, E. Cimini, D. TI Aneuploidy confers a selective advantage to cancer cells by promoting karyotypic heterogeneity. SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 [Rutledge, S. D.; Kantzler, C. L.; Cimini, D.] Virginia Tech, Biol Sci, Blacksburg, VA USA. [Rutledge, S. D.; Kantzler, C. L.; Kale, S. D.; Cimini, D.] Virginia Tech, Virginia Bioinformat Inst, Blacksburg, VA USA. [Douglas, T. A.] Virginia Tech, Sch Biomed Engn & Sci, Blacksburg, VA USA. [Wangsa, D.] NCI, Genet Branch, NIH, Bethesda, MD 20892 USA. [Logarinho, E.] Univ Porto, Inst Biol Mol & Celular, Oporto, Portugal. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 EI 1939-4586 J9 MOL BIOL CELL JI Mol. Biol. Cell PY 2015 VL 26 MA M17 PG 2 WC Cell Biology SC Cell Biology GA V47BX UT WOS:000209928400064 ER PT J AU Satpute-krishnan, P Park, BS Lippincott-Schwartz, J AF Satpute-krishnan, P. Park, B. S. Lippincott-Schwartz, J. TI Quality control of GPI-anchored proteins at the plasma membrane. SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 [Satpute-krishnan, P.; Park, B. S.; Lippincott-Schwartz, J.] NICHD, Cell Biol & Metab Program, NIH, Bethesda, MD USA. [Park, B. S.] Thomas Jefferson High Sch Sci & Technol, Alexandria, VA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 EI 1939-4586 J9 MOL BIOL CELL JI Mol. Biol. Cell PY 2015 VL 26 MA M211 PG 1 WC Cell Biology SC Cell Biology GA V47BX UT WOS:000209928401007 ER PT J AU Satpute-krishnan, P Park, BS Lippincott-Schwartz, J AF Satpute-krishnan, P. Park, B. S. Lippincott-Schwartz, J. TI Quality control of GPI-anchored proteins at the plasma membrane SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 [Satpute-krishnan, P.; Park, B. S.; Lippincott-Schwartz, J.] NICHD, Cell Biol & Metab Program, NIH, Bethesda, MD USA. [Park, B. S.] Thomas Jefferson High Sch Sci & Technol, Alexandria, VA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 EI 1939-4586 J9 MOL BIOL CELL JI Mol. Biol. Cell PY 2015 VL 26 MA P2276 PG 2 WC Cell Biology SC Cell Biology GA V47BZ UT WOS:000209928600540 ER PT J AU Schoborg, T Zajac, AL Fagerstrom, CJ Guillen, RX Rusan, NM AF Schoborg, T. Zajac, A. L. Fagerstrom, C. J. Guillen, R. X. Rusan, N. M. TI Centrosome-Pole Cohesion Requires Abnormal Spindle and Calmodulin to Ensure Proper Centrosome Inheritance in Neural Stem Cells SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 [Schoborg, T.; Zajac, A. L.; Fagerstrom, C. J.; Guillen, R. X.; Rusan, N. M.] NHLBI, Cell Biol Physiol Ctr, Bldg 10, Bethesda, MD 20892 USA. [Zajac, A. L.] Univ Chicago, Dept Mol Genet & Cell Biol, Chicago, IL 60637 USA. [Guillen, R. X.] Vanderbilt Univ, Sch Med, Dept Cell & Dev Biol, Nashville, TN 37212 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 EI 1939-4586 J9 MOL BIOL CELL JI Mol. Biol. Cell PY 2015 VL 26 MA P215 PG 1 WC Cell Biology SC Cell Biology GA V47BX UT WOS:000209928401242 ER PT J AU Scott, BL Bailey, EM Sochaki, KA Low-Nam, ST Kerkvliet, JG Taraska, JW Hoppe, AD AF Scott, B. L. Bailey, E. M. Sochaki, K. A. Low-Nam, S. T. Kerkvliet, J. G. Taraska, J. W. Hoppe, A. D. TI Imaging Sub-Diffraction Membrane Bending Dynamics During Clathrin-Mediated Endocytosis SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 [Scott, B. L.; Bailey, E. M.; Kerkvliet, J. G.; Hoppe, A. D.] South Dakota State Univ, Chem & Biochem, Brookings, SD 57007 USA. [Sochaki, K. A.; Taraska, J. W.] NHLBI, NIH, Bethesda, MD 20892 USA. [Low-Nam, S. T.] Univ Calif Berkeley, Chem, Berkeley, CA 94720 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 EI 1939-4586 J9 MOL BIOL CELL JI Mol. Biol. Cell PY 2015 VL 26 MA P854 PG 2 WC Cell Biology SC Cell Biology GA V47BY UT WOS:000209928500045 ER PT J AU Sengupta, P Cruz, A Siegel, R Lippincott-Schwartz, J AF Sengupta, P. Cruz, A. Siegel, R. Lippincott-Schwartz, J. TI Nanoscale spatiotemporal organization of Fas receptor (CD95) during early stages of signaling revealed by quantitative superresolution microscopy. SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 [Sengupta, P.; Lippincott-Schwartz, J.] NICHD, CBMP, Bethesda, MD USA. [Cruz, A.; Siegel, R.] NIAMS, Autoimmun Branch, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 EI 1939-4586 J9 MOL BIOL CELL JI Mol. Biol. Cell PY 2015 VL 26 MA E20 PG 2 WC Cell Biology SC Cell Biology GA V47BX UT WOS:000209928400026 ER PT J AU Seo, AY Lau, P Feliciano, D Le Gros, MA Cinquin, B Larabell, CA Lippincott-Schwartz, J AF Seo, A. Y. Lau, P. Feliciano, D. Le Gros, M. A. Cinquin, B. Larabell, C. A. Lippincott-Schwartz, J. TI Snf1p Activation Redistributes Atg14p onto the Vacuole to Trigger Lipid Droplet Autophagy upon Glucose Restriction in Budding Yeast SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 [Seo, A. Y.; Lau, P.; Feliciano, D.; Lippincott-Schwartz, J.] NICHHD, NIH, Bethesda, MD 20892 USA. [Le Gros, M. A.; Cinquin, B.; Larabell, C. A.] Univ Calif San Francisco, Dept Anat, San Francisco, CA 94143 USA. [Le Gros, M. A.; Larabell, C. A.] Lawrence Berkeley Natl Lab, Phys Biosci Div, Berkeley, CA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 EI 1939-4586 J9 MOL BIOL CELL JI Mol. Biol. Cell PY 2015 VL 26 MA P1464 PG 1 WC Cell Biology SC Cell Biology GA V47BY UT WOS:000209928500650 ER PT J AU Shachar, S Burman, B Voss, TC Misteli, T Pegoraro, G AF Shachar, S. Burman, B. Voss, T. C. Misteli, T. Pegoraro, G. TI High-throughput imaging for the systematic spatial analysis of genomic positioning SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 [Shachar, S.; Burman, B.; Misteli, T.] NCI, Cell Biol Genomes Grp, NIH, Bethesda, MD 20892 USA. [Voss, T. C.; Pegoraro, G.] NCI, HiTIF, NIH, Bethesda, MD 20892 USA. [Voss, T. C.] PerkinElmer, Waltham, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 EI 1939-4586 J9 MOL BIOL CELL JI Mol. Biol. Cell PY 2015 VL 26 MA P1615 PG 1 WC Cell Biology SC Cell Biology GA V47BY UT WOS:000209928500809 ER PT J AU Shitara, A Tora, MS Weigert, R AF Shitara, A. Tora, M. S. Weigert, R. TI Assembly of the actin cytoskeleton during regulated exocytosis in salivary gland of live rodents SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 [Shitara, A.; Tora, M. S.; Weigert, R.] Natl Inst Dent & Craniofacial Res, NIH, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 EI 1939-4586 J9 MOL BIOL CELL JI Mol. Biol. Cell PY 2015 VL 26 MA P1657 PG 1 WC Cell Biology SC Cell Biology GA V47BY UT WOS:000209928500851 ER PT J AU Shu, S Liu, X Billington, N Yu, S Williamson, CD Brezska, HB Donaldson, J Sellers, JR Korn, ED AF Shu, S. Liu, X. Billington, N. Yu, S. Williamson, C. D. Brezska, H. B. Donaldson, J. Sellers, J. R. Korn, E. D. TI Mammalian nonmuscle myosin IIs bind to anionic phospholipid liposomes via the regulatory light chain binding site SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 [Shu, S.; Liu, X.; Yu, S.; Williamson, C. D.; Brezska, H. B.; Donaldson, J.; Korn, E. D.] NHLBI, Lab Cell Biol, CBCP Ctr, NIH, Betesda, MD USA. [Billington, N.; Sellers, J. R.] NHLBI, Lab Mol Physiol, CBCP 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 PY 2015 VL 26 MA P1724 PG 2 WC Cell Biology SC Cell Biology GA V47BY UT WOS:000209928500918 ER PT J AU Shukla, AK Kong, D Sharma, M Loncarek, J AF Shukla, A. K. Kong, D. Sharma, M. Loncarek, J. TI Plk1 relieves centriole block to reduplication by promoting daughter centriole maturation. SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 [Shukla, A. K.; Kong, D.; Sharma, M.; Loncarek, J.] NCI, Lab Prot Dynam & Signaling, CCR, NIH, Frederick, MD 21701 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 EI 1939-4586 J9 MOL BIOL CELL JI Mol. Biol. Cell PY 2015 VL 26 MA P213 PG 2 WC Cell Biology SC Cell Biology GA V47BX UT WOS:000209928401240 ER PT J AU Skau, CT Thiam, HR Alushin, GM Gurel, P Tubbs, A Piel, M Nussenzweig, A Waterman, CM AF Skau, C. T. Thiam, H. Racine Alushin, G. M. Gurel, P. Tubbs, A. Piel, M. Nussenzweig, A. Waterman, C. M. TI A novel actin-adhesion structure requiring the formin FMN2 positions the nucleus and protects it from DNA damage during confined migration SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 [Skau, C. T.; Thiam, H. Racine; Alushin, G. M.; Gurel, P.; Waterman, C. M.] NHLBI, NIH, Bethesda, MD 20892 USA. [Tubbs, A.; Nussenzweig, A.] NCI, NIH, Bethesda, MD 20892 USA. [Piel, M.] Inst Curie, Syst Cell Biol Cell Polar & Cell Div, Paris, France. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 EI 1939-4586 J9 MOL BIOL CELL JI Mol. Biol. Cell PY 2015 VL 26 MA P57 PG 2 WC Cell Biology SC Cell Biology GA V47BX UT WOS:000209928401084 ER PT J AU Skau, CT Thiam, HR Alushin, GM Gurel, P Tubbs, A Piel, M Nussenzweig, A Waterman, CM AF Skau, C. T. Thiam, H. Racine Alushin, G. M. Gurel, P. Tubbs, A. Piel, M. Nussenzweig, A. Waterman, C. M. TI A novel actin-adhesion structure requiring the formin FMN2 positions the nucleus and protects it from DNA damage during confined migration. SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 [Skau, C. T.; Thiam, H. Racine; Alushin, G. M.; Gurel, P.; Waterman, C. M.] NHLBI, NIH, Bethesda, MD 20892 USA. [Tubbs, A.; Nussenzweig, A.] NCI, NIH, Bethesda, MD 20892 USA. [Piel, M.] Inst Curie, Syst Cell Biol Cell Polar & Cell Div, Paris, France. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 EI 1939-4586 J9 MOL BIOL CELL JI Mol. Biol. Cell PY 2015 VL 26 MA E3 PG 1 WC Cell Biology SC Cell Biology GA V47BX UT WOS:000209928400009 ER PT J AU Sohn, M Ivanova, PT Brown, AH Kim, Y Balla, T AF Sohn, M. Ivanova, P. T. Brown, A. H. Kim, Y. Balla, T. TI A TIGHT METABOLIC RELATIONSHIP BETWEEN PHOSPHATIDYLINOSITOL 4-PHOSPHATE TURNOVER AND PHOSPHATIDYSERINE SYNTHESIS. SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 [Sohn, M.; Kim, Y.; Balla, T.] NICHD, NIH, Bethesda, MD USA. [Ivanova, P. T.; Brown, A. H.] Vanderbilt Univ, Sch Med, Vanderbilt Ingram Canc Ctr, Dept Pharmacol & Biochem, Nashville, TN 37212 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 EI 1939-4586 J9 MOL BIOL CELL JI Mol. Biol. Cell PY 2015 VL 26 MA P474 PG 2 WC Cell Biology SC Cell Biology GA V47BX UT WOS:000209928402084 ER PT J AU Sohn, M Ivanova, PT Brown, AH Kim, Y Balla, T AF Sohn, M. Ivanova, P. T. Brown, A. H. Kim, Y. Balla, T. TI A TIGHT METABOLIC RELATIONSHIP BETWEEN PHOSPHATIDYLINOSITOL 4-PHOSPHATE TURNOVER AND PHOSPHATIDYSERINE SYNTHESIS. SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 [Sohn, M.; Kim, Y.; Balla, T.] NICHD, NIH, Bethesda, MD USA. [Ivanova, P. T.; Brown, A. H.] Vanderbilt Univ, Sch Med, Vanderbilt Ingram Canc Ctr, Dept Pharmacol & Biochem, Nashville, TN 37212 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 EI 1939-4586 J9 MOL BIOL CELL JI Mol. Biol. Cell PY 2015 VL 26 MA M72 PG 2 WC Cell Biology SC Cell Biology GA V47BX UT WOS:000209928400168 ER PT J AU Somasundaram, A Taraska, JW AF Somasundaram, A. Taraska, J. W. TI Investigating Protein Dynamics At Sites Of Exocytosis In Live Cells SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 [Somasundaram, A.; 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 PY 2015 VL 26 MA P387 PG 1 WC Cell Biology SC Cell Biology GA V47BX UT WOS:000209928401414 ER PT J AU Staunton, JR Blehm, BH Tanner, K AF Staunton, J. R. Blehm, B. H. Tanner, K. TI Linking microscale heterogeneities to material properties-microscale topography and nanoscale frequency-dependent stress-strain responses in surrogate hydrogels to mimic the stromal microenvironment SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 [Staunton, J. R.; Blehm, B. H.; Tanner, K.] NCI, Cell Biol Lab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 EI 1939-4586 J9 MOL BIOL CELL JI Mol. Biol. Cell PY 2015 VL 26 MA P598 PG 1 WC Cell Biology SC Cell Biology GA V47BX UT WOS:000209928402207 ER PT J AU Staunton, JR Blehm, BH Devine, A Tanner, K AF Staunton, J. R. Blehm, B. H. Devine, A. Tanner, K. TI aMOTIV microscopy: mechanical characterization of the in vitro and in vivo tissue microenvironment. SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 [Staunton, J. R.; Blehm, B. H.; Devine, A.; Tanner, 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 PY 2015 VL 26 MA M140 PG 2 WC Cell Biology SC Cell Biology GA V47BX UT WOS:000209928400291 ER PT J AU Sulkowski, MJ Han, T Ott, CM Verheyen, EM Lippincott-Schwartz, J Serpe, M AF Sulkowski, M. J. Han, T. Ott, C. M. Verheyen, E. M. Lippincott-Schwartz, J. Serpe, M. TI A novel, noncanonical BMP pathway modulates synapse maturation at the Drosophila neuromuscular junction. SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 [Sulkowski, M. J.; Han, T.; Ott, C. M.; Lippincott-Schwartz, J.; Serpe, M.] NICHD, NIH, Bethesda, MD USA. [Verheyen, E. M.] Simon Fraser Univ, Dept Mol Biol & Biochem, Burnaby, BC, 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 PY 2015 VL 26 MA M223 PG 2 WC Cell Biology SC Cell Biology GA V47BX UT WOS:000209928401019 ER PT J AU Swaminathan, V Mathew, JK Nordenfelt, P Mehta, SB Moore, TI Nobuyasu, K Tani, T Mayor, S Springer, TA Waterman, CM AF Swaminathan, V. Mathew, J. K. Nordenfelt, P. Mehta, S. B. Moore, T. I. Nobuyasu, K. Tani, T. Mayor, S. Springer, T. A. Waterman, C. M. TI Actin retrograde flow orients and aligns activated, ligand-engaged integrins in focal adhesions. SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 [Swaminathan, V.; Waterman, C. M.] NHLBI, Cell Biol & Physiol Ctr, NIH, Bethesda, MD 20892 USA. [Mathew, J. K.; Mayor, S.] Natl Ctr Biol Sci, Bangalore, Karnataka, India. [Nordenfelt, P.] Lund Univ, Div Infect Med, Lund, Sweden. [Mehta, S. B.; Tani, T.] Marine Biol Lab, Woods Hole, MA 02543 USA. [Moore, T. I.; Springer, T. A.] Harvard Med Sch, Dept Biol Chem & Mol Pharmacol, Boston, MA USA. [Moore, T. I.; Springer, T. A.] Harvard Med Sch, Dept Med, Boston, MA USA. [Nobuyasu, K.] Inst Mol Sci, Okazaki, Aichi, Japan. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 EI 1939-4586 J9 MOL BIOL CELL JI Mol. Biol. Cell PY 2015 VL 26 MA P2228 PG 2 WC Cell Biology SC Cell Biology GA V47BZ UT WOS:000209928600493 ER PT J AU Tang, Q Billington, N Bookwalter, C Lord, MJ Trybus, KM AF Tang, Q. Billington, N. Bookwalter, C. Lord, M. J. Trybus, K. M. TI A single-headed fission yeast myosin V transports actin in a tropomyosin-dependent manner SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 [Tang, Q.; Bookwalter, C.; Lord, M. J.; Trybus, K. M.] Univ Vermont, Mol Physiol & Biophys, Burlington, VT USA. [Billington, N.] NHLBI, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 EI 1939-4586 J9 MOL BIOL CELL JI Mol. Biol. Cell PY 2015 VL 26 MA P1714 PG 2 WC Cell Biology SC Cell Biology GA V47BY UT WOS:000209928500908 ER PT J AU Thiam, HR Waterman, CM AF Thiam, H. R. Waterman, C. M. TI Spatiotemporal regulation of focal adhesion disassembly at mitosis SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 [Thiam, H. R.; Waterman, C. M.] 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 PY 2015 VL 26 MA P1809 PG 1 WC Cell Biology SC Cell Biology GA V47BZ UT WOS:000209928600084 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 C1 [Valm, A. M.; Cohen, S.; Lippincott-Schwartz, J.] NICHD, NIH, Bethesda, MD USA. [Legant, W. R.; Betzig, E.] Howard Hughes Med Inst, Janelia Farm, Ashburn, VA USA. [Davidson, M. W.] Florida State Univ, Natl High Magnet Field Lab, Tallahassee, DC USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 EI 1939-4586 J9 MOL BIOL CELL JI Mol. Biol. Cell PY 2015 VL 26 MA P1628 PG 2 WC Cell Biology SC Cell Biology GA V47BY UT WOS:000209928500822 ER PT J AU Van der Bliek, AM Youle, R AF Van der Bliek, A. M. Youle, R. TI Role of Fis1 in mitochondrial fission and stress. SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 [Van der Bliek, A. M.] Univ Calif Los Angeles, David Geffen Sch Med, Biol Chem, Los Angeles, CA 90095 USA. [Youle, R.] 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 PY 2015 VL 26 MA M217 PG 2 WC Cell Biology SC Cell Biology GA V47BX UT WOS:000209928401013 ER PT J AU Vecchiarelli, AG AF Vecchiarelli, A. G. TI Cytoplasmic MinD Depletion and a MinD/MinE Stoichiometric Toggle Switch on the Membrane Drive Min Oscillation SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 [Vecchiarelli, A. G.] NIDDK, NIH, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 EI 1939-4586 J9 MOL BIOL CELL JI Mol. Biol. Cell PY 2015 VL 26 MA P1580 PG 1 WC Cell Biology SC Cell Biology GA V47BY UT WOS:000209928500765 ER PT J AU Vemu, A Atherton, J Spector, JO Szyk, A Moores, CA Roll-Mecak, A AF Vemu, A. Atherton, J. Spector, J. O. Szyk, A. Moores, C. A. Roll-Mecak, A. TI In vitro dynamics with engineered recombinant human tubulin reveal mechanism of regulation by the intrinsically disordered C-terminal tails SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 [Vemu, A.; Spector, J. O.; Szyk, A.; Roll-Mecak, A.] NINDS, Cell Biol & Biophys Unit, NIH, Bethesda, MD 20892 USA. [Atherton, J.; Moores, C. A.] Univ London, Inst Struct & Mol Biol, Dept Biol Sci, Birkbeck Coll, London, England. [Roll-Mecak, A.] NHLBI, Biophys 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 PY 2015 VL 26 MA P956 PG 1 WC Cell Biology SC Cell Biology GA V47BY UT WOS:000209928500145 ER PT J AU Walia, V Insinna, C Lu, Q Specht, S Meng, Z Zhou, M Ritt, D Morrison, D Westlake, CJ AF Walia, V. Insinna, C. Lu, Q. Specht, S. Meng, Z. Zhou, M. Ritt, D. Morrison, D. Westlake, C. J. TI Akt stabilizes a Rab11-WDR44 interaction to regulate pre-ciliary vesicle trafficking and ciliogenesis initiation. SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 [Walia, V.; Insinna, C.; Lu, Q.; Specht, S.; Meng, Z.; Zhou, M.; Ritt, D.; Morrison, D.; Westlake, C. J.] NCI, Frederick, MD 21701 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 EI 1939-4586 J9 MOL BIOL CELL JI Mol. Biol. Cell PY 2015 VL 26 MA P157 PG 1 WC Cell Biology SC Cell Biology GA V47BX UT WOS:000209928401185 ER PT J AU Walia, V Insinna, C Lu, Q Specht, S Meng, Z Zhou, M Ritt, D Morrison, D Westlake, CJ AF Walia, V. Insinna, C. Lu, Q. Specht, S. Meng, Z. Zhou, M. Ritt, D. Morrison, D. Westlake, C. J. TI Akt stabilizes a Rab11-WDR44 interaction to regulate pre-ciliary vesicle trafficking and ciliogenesis initiation. SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 [Walia, V.; Insinna, C.; Lu, Q.; Specht, S.; Meng, Z.; Zhou, M.; Ritt, D.; Morrison, D.; Westlake, C. J.] NCI, Frederick, MD 21701 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 EI 1939-4586 J9 MOL BIOL CELL JI Mol. Biol. Cell PY 2015 VL 26 MA E60 PG 1 WC Cell Biology SC Cell Biology GA V47BX UT WOS:000209928400132 ER PT J AU Webster, MT Manor, U Lippincott-Schwartz, J Fan, C AF Webster, M. T. Manor, U. Lippincott-Schwartz, J. Fan, C. TI Intravital Imaging Reveals Ghost Fibers as Architectural Units Guiding Muscle Progenitors During Skeletal Muscle Regeneration. SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 [Webster, M. T.; Fan, C.] Carnegie Inst Sci, Embryol, Baltimore, MD USA. [Manor, U.; Lippincott-Schwartz, J.] 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 PY 2015 VL 26 MA P673 PG 1 WC Cell Biology SC Cell Biology GA V47BX UT WOS:000209928402282 ER PT J AU Webster, MT Manor, U Lippincott-Schwartz, J Fan, C AF Webster, M. T. Manor, U. Lippincott-Schwartz, J. Fan, C. TI Intravital Imaging Reveals Ghost Fibers as Architectural Units Guiding Muscle Progenitors During Skeletal Muscle Regeneration. SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 [Webster, M. T.; Fan, C.] Carnegie Inst Sci, Embryol, Baltimore, MD USA. [Manor, U.; Lippincott-Schwartz, J.] 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 PY 2015 VL 26 MA M7 PG 1 WC Cell Biology SC Cell Biology GA V47BX UT WOS:000209928400054 ER PT J AU Williamson, CD Donaldson, JG AF Williamson, C. D. Donaldson, J. G. TI Dynein and microtubules capture newly-formed macropinosomes for transport through the actin-rich lamellae and subsequent sorting of cargo and membrane SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 [Williamson, C. D.; Donaldson, J. G.] NHLBI, Cell Biol & Physiol Ctr, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 EI 1939-4586 J9 MOL BIOL CELL JI Mol. Biol. Cell PY 2015 VL 26 MA P1219 PG 1 WC Cell Biology SC Cell Biology GA V47BY UT WOS:000209928500407 ER PT J AU Wolyniak, MJ Prunuske, AJ Adler, JJ Crowe, AJ Keller, LC Kolber, BJ Leland, BA Murugesan, S Schreiner, SM Whatley, Z Wick, SM AF Wolyniak, M. J. Prunuske, A. J. Adler, J. J. Crowe, A. J. Keller, L. C. Kolber, B. J. Leland, B. A. Murugesan, S. Schreiner, S. M. Whatley, Z. Wick, S. M. TI Spreading Vision and Change Through Faculty Mentorship: The ASCB Mentoring in Active Learning and Teaching (MALT) program. SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 [Wolyniak, M. J.] Hampden Sydney Coll, Biol, Hampden Sydney, VA 23943 USA. [Prunuske, A. J.] Univ Minnesota, Sch Med, Biomed Sci, Duluth, MN 55812 USA. [Adler, J. J.] Univ Brescia, Biol, Owensboro, KY USA. [Crowe, A. J.] Univ Washington, Biol, Seattle, WA 98195 USA. [Keller, L. C.] Quinnipiac Univ, Biol Sci, Hamden, CT USA. [Kolber, B. J.] Duquesne Univ, Biol Sci, Pittsburgh, PA 15219 USA. [Leland, B. A.; Schreiner, S. M.] Yale Univ, Sch Med, Cell Biol, New Haven, CT USA. [Murugesan, S.] NHLBI, Cell Biol & Physiol, Bethesda, MD 20892 USA. [Whatley, Z.] Gettysburg Coll, Biol, Gettysburg, PA 17325 USA. [Wick, S. M.] Univ Minnesota, Plant Biol, St Paul, MN 55108 USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 EI 1939-4586 J9 MOL BIOL CELL JI Mol. Biol. Cell PY 2015 VL 26 MA M56 PG 2 WC Cell Biology SC Cell Biology GA V47BX UT WOS:000209928400103 ER PT J AU Wolyniak, MJ Prunuske, AJ Adler, JJ Crowe, AJ Keller, LC Kolber, BJ Leland, BA Murugesan, S Schreiner, SM Whatley, Z Wick, SM AF Wolyniak, M. J. Prunuske, A. J. Adler, J. J. Crowe, A. J. Keller, L. C. Kolber, B. J. Leland, B. A. Murugesan, S. Schreiner, S. M. Whatley, Z. Wick, S. M. TI Spreading Vision and Change Through Faculty Mentorship: The ASCB Mentoring in Active Learning and Teaching (MALT) program SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 [Wolyniak, M. J.] Hampden Sydney Coll, Biol, Hampden Sydney, VA 23943 USA. [Prunuske, A. J.] Univ Minnesota, Sch Med, Biomed Sci, Duluth, MN 55812 USA. [Adler, J. J.] Univ Brescia, Biol, Owensboro, KY USA. [Crowe, A. J.] Univ Washington, Biol, Seattle, WA 98195 USA. [Keller, L. C.] Quinnipiac Univ, Biol Sci, Hamden, CT USA. [Kolber, B. J.] Duquesne Univ, Biol Sci, Pittsburgh, PA 15219 USA. [Leland, B. A.; Schreiner, S. M.] Yale Univ, Sch Med, Cell Biol, New Haven, CT USA. [Murugesan, S.] NHLBI, Cell Biol & Physiol, Bethesda, MD 20892 USA. [Whatley, Z.] Gettysburg Coll, Biol, Gettysburg, PA 17325 USA. [Wick, S. M.] Univ Minnesota, Plant Biol, St Paul, MN 55108 USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 EI 1939-4586 J9 MOL BIOL CELL JI Mol. Biol. Cell PY 2015 VL 26 MA P816 PG 2 WC Cell Biology SC Cell Biology GA V47BY UT WOS:000209928500008 ER PT J AU Xie, Y Zhou, B Lin, M Wang, S Sheng, Z AF Xie, Y. Zhou, B. Lin, M. Wang, S. Sheng, Z. TI Endolysosomal Deficits Augment Mitochondria Pathology in Spinal Motor Neurons of Asymptomatic fALS Mice. SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 [Xie, Y.; Zhou, B.; Lin, M.; Wang, S.; Sheng, Z.] NINDS, NIH, Rockville, MD USA. FU Intramural Research Program of NINDS, NIH FX Supported by the Intramural Research Program of NINDS, NIH NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 EI 1939-4586 J9 MOL BIOL CELL JI Mol. Biol. Cell PY 2015 VL 26 MA P344 PG 2 WC Cell Biology SC Cell Biology GA V47BX UT WOS:000209928401371 ER PT J AU Xie, Y Zhou, B Lin, M Wang, S Sheng, Z AF Xie, Y. Zhou, B. Lin, M. Wang, S. Sheng, Z. TI Endolysosomal Deficits Augment Mitochondria Pathology in Spinal Motor Neurons of Asymptomatic fALS Mice. SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 [Xie, Y.; Zhou, B.; Lin, M.; Wang, S.; Sheng, Z.] NINDS, NIH, Rockville, MD USA. FU NINDS, NIH FX Supported by the Intramural Research Program of NINDS, NIH NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 EI 1939-4586 J9 MOL BIOL CELL JI Mol. Biol. Cell PY 2015 VL 26 MA E63 PG 2 WC Cell Biology SC Cell Biology GA V47BX UT WOS:000209928400135 ER PT J AU Young, DJ Guydosh, NR Zhang, F Hinnebusch, AG Green, R AF Young, D. J. Guydosh, N. R. Zhang, F. Hinnebusch, A. G. Green, R. TI Rli1/ABCE1 Recycles Terminating Ribosomes and Controls Translation Reinitiation in 3 ' UTRs In Vivo SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 [Young, D. J.; Zhang, F.; Hinnebusch, A. G.] NIH, Lab Gene Regulat & Dev, Bethesda, MD 20892 USA. [Guydosh, N. R.; Green, R.] Johns Hopkins Univ, Sch Med, Mol Biol & Genet, 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 PY 2015 VL 26 MA P1168 PG 2 WC Cell Biology SC Cell Biology GA V47BY UT WOS:000209928500356 ER PT J AU Yu, L Das, P Vall, A Yan, Y Gao, X Sifre, M Castro, L Kissling, GE Moore, AB Dixon, D AF Yu, L. Das, P. Vall, A. Yan, Y. Gao, X. Sifre, M. Castro, L. Kissling, G. E. Moore, A. B. Dixon, D. TI Cell proliferation induced by a low dose of Bisphenol A through nongenomic signaling via membrane-associated estrogen receptor alpha 36 in human uterine leiomyoma cells SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 [Yu, L.; Das, P.; Vall, A.; Yan, Y.; Gao, X.; Castro, L.; Moore, A. B.; Dixon, D.] NIEHS, Mol Pathogenesis Grp, NTPL, Res Triangle Pk, NC 27709 USA. [Sifre, M.] NIEHS, Flow Cytometry Ctr, Lab Signal Transduct, Res Triangle Pk, NC 27709 USA. [Kissling, G. E.] NIEHS, Biostat & Computat Biol Branch, Res Triangle Pk, NC 27709 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 EI 1939-4586 J9 MOL BIOL CELL JI Mol. Biol. Cell PY 2015 VL 26 MA P2146 PG 2 WC Cell Biology SC Cell Biology GA V47BZ UT WOS:000209928600420 ER PT J AU Zaal, KJ Oddoux, S Kenea, A Randazzo, D Ralston, E AF Zaal, K. J. Oddoux, S. Kenea, A. Randazzo, D. Ralston, E. TI Changes in polarity of Golgi complexes contribute to microtubule defects in mdx muscle, the murine model for Duchenne muscular dystrophy SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 [Zaal, K. J.; Oddoux, S.; Kenea, A.; Randazzo, D.; Ralston, E.] NIAMS, Light Imaing Sect, NIH, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 EI 1939-4586 J9 MOL BIOL CELL JI Mol. Biol. Cell PY 2015 VL 26 MA P2425 PG 2 WC Cell Biology SC Cell Biology GA V47BZ UT WOS:000209928600688 ER PT J AU Battle, KE Guerra, CA Golding, N Duda, KA Cameron, E Howes, RE Elyazar, IRF Baird, JK Reiner, RC Gething, PW Smith, DL Hay, SI AF Battle, Katherine E. Guerra, Carlos A. Golding, Nick Duda, Kirsten A. Cameron, Ewan Howes, Rosalind E. Elyazar, Iqbal R. F. Baird, J. Kevin Reiner, Robert C., Jr. Gething, Peter W. Smith, David L. Hay, Simon I. TI Global database of matched Plasmodium falciparum and P-vivax incidence and prevalence records from 1985-2013 SO SCIENTIFIC DATA LA English DT Article AB Measures of clinical incidence are necessary to help estimate the burden of a disease. Incidence is a metric not commonly measured in malariology because the longitudinal surveys required are costly and labour intensive. This database is an effort to collate published incidence records obtained using active case detection for Plasmodium falciparum and Plasmodium vivax malaria. The literature search methods, data abstraction procedures and data processing procedures are described here. A total of 1,680 spatio-temporally unique incidence records were collected for the database: 1,187 for P. falciparum and 493 for P. vivax. These data were gathered to model the relationship between clinical incidence and prevalence of infection and can be used for a variety of modelling exercises including the assessment of change in disease burden in relation to age and control interventions. The subset of data that have been used for such modelling exercises are described and identified. C1 [Battle, Katherine E.; Golding, Nick; Duda, Kirsten A.; Cameron, Ewan; Howes, Rosalind E.; Gething, Peter W.; Smith, David L.; Hay, Simon I.] Univ Oxford, Dept Zool, Spatial Ecol & Epidemiol Grp, Tinbergen Bldg,South Parks Rd, Oxford OX1 3PS, England. [Guerra, Carlos A.] Sanaria Inst Global Hlth & Trop Med, Rockville, MD 20850 USA. [Elyazar, Iqbal R. F.; Baird, J. Kevin] Eijkman Oxford Clin Res Unit, Jakarta 10430, Indonesia. [Baird, J. Kevin] Univ Oxford, Nuffield Dept Med, Ctr Trop Med, Oxford OX3 7FZ, England. [Reiner, Robert C., Jr.] Indiana Univ, Sch Publ Hlth, Bloomington, IN 47405 USA. [Smith, David L.; Hay, Simon I.] NIH, Fogarty Int Ctr, Bethesda, MD 20892 USA. RP Battle, KE (reprint author), Univ Oxford, Dept Zool, Spatial Ecol & Epidemiol Grp, Tinbergen Bldg,South Parks Rd, Oxford OX1 3PS, England. EM katherine.battle@zoo.ox.ac.uk OI Golding, Nick/0000-0001-8916-5570; Hay, Simon/0000-0002-0611-7272; Gething, Peter/0000-0001-6759-5449; Battle, Katherine/0000-0003-2401-2615 FU Wellcome Trust [095066, B9RJIXO, B9RZGS0]; Bill & Melinda Gates Foundation [OPP1053338, OPP1068048, OPP1110495]; RAPIDD program of the Science & Technology Directorate, Department of Homeland Security; Fogarty International Center, National Institutes of Health FX S.I.H. is funded by a Senior Research Fellowship from the Wellcome Trust (095066), which also supports K.E.B., C.A.G., K.A.D. and R.E.H. N.G. is funded by a grant from the Bill & Melinda Gates Foundation (OPP1053338). J.K.B. is supported by Wellcome Trust grant (B9RJIXO). I.R.F.E. is funded by a Public Health and Tropical Medicine Fellowship of the Wellcome Trust (B9RZGS0). P.W.G. is a Medical Research Council Career Development Fellow (K00669X) and receives support from the Bill and Melinda Gates Foundation (OPP1068048), which also supports E.C. D.L.S. is funded by a grant from the Bill & Melinda Gates Foundation (OPP1110495), which also supports R.C.R. R.C.R., D.L.S. and S.I.H. also acknowledge funding support from the RAPIDD program of the Science & Technology Directorate, Department of Homeland Security, and the Fogarty International Center, National Institutes of Health. The authors also thank Joshua Longbottom his for proof-reading and comments. NR 33 TC 4 Z9 4 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 2052-4463 J9 SCI DATA JI Sci. Data PY 2015 VL 2 AR 150012 DI 10.1038/sdata.2015.12 PG 12 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA V45VM UT WOS:000209844100007 ER PT J AU Kraemer, MUG Sinka, ME Duda, KA Mylne, A Shearer, FM Brady, OJ Messina, JP Barker, CM Moore, CG Carvalho, RG Coelho, GE Van Bortel, W Hendrickx, G Schaffner, F Wint, GRW Elyazar, IRF Teng, HJ Hay, SI AF Kraemer, Moritz U. G. Sinka, Marianne E. Duda, Kirsten A. Mylne, Adrian Shearer, Freya M. Brady, Oliver J. Messina, Jane P. Barker, Christopher M. Moore, Chester G. Carvalho, Roberta G. Coelho, Giovanini E. Van Bortel, Wim Hendrickx, Guy Schaffner, Francis Wint, G. R. William Elyazar, Iqbal R. F. Teng, Hwa-Jen Hay, Simon I. TI The global compendium of Aedes aegypti and Ae. albopictus occurrence SO SCIENTIFIC DATA LA English DT Article AB Aedes aegypti and Ae. albopictus are the main vectors transmitting dengue and chikungunya viruses. Despite being pathogens of global public health importance, knowledge of their vectors' global distribution remains patchy and sparse. A global geographic database of known occurrences of Ae. aegypti and Ae. albopictus between 1960 and 2014 was compiled. Herein we present the database, which comprises occurrence data linked to point or polygon locations, derived from peer-reviewed literature and unpublished studies including national entomological surveys and expert networks. We describe all data collection processes, as well as geo-positioning methods, database management and quality-control procedures. This is the first comprehensive global database of Ae. aegypti and Ae. albopictus occurrence, consisting of 19,930 and 22,137 geo-positioned occurrence records respectively. Both datasets can be used for a variety of mapping and spatial analyses of the vectors and, by inference, the diseases they transmit. C1 [Kraemer, Moritz U. G.; Duda, Kirsten A.; Messina, Jane P.; Wint, G. R. William; Hay, Simon I.] Univ Oxford, Dept Zool, Spatial Ecol & Epidemiol Grp, South Pk Rd, Oxford OX1 3PS, England. [Sinka, Marianne E.; Mylne, Adrian; Shearer, Freya M.; Brady, Oliver J.] Univ Oxford, Wellcome Trust Ctr Human Genet, Oxford, England. [Sinka, Marianne E.; Mylne, Adrian; Shearer, Freya M.; Brady, Oliver J.] Univ Washington, Inst Hlth Metr & Evaluat, Seattle, WA 98195 USA. [Barker, Christopher M.] Univ Calif Davis, Sch Vet Med, Dept Pathol Microbiol & Immunol, Davis, CA 95616 USA. [Barker, Christopher M.] Univ Calif Davis, Ctr Vectorborne Dis, Davis, CA 95616 USA. [Barker, Christopher M.; Hay, Simon I.] NIH, Fogarty Int Ctr, Bethesda, MD 20892 USA. [Moore, Chester G.] Colorado State Univ, Dept Microbiol Immunol & Pathol, Ft Collins, CO 80523 USA. [Carvalho, Roberta G.; Coelho, Giovanini E.] Minist Hlth, Natl Dengue Control Program, Brasilia, DF, Brazil. [Van Bortel, Wim] European Ctr Dis Prevent & Control, Stockholm, Sweden. [Hendrickx, Guy; Schaffner, Francis] Avia GIS, Zoersel, Belgium. [Wint, G. R. William] Environm Res Grp Oxford Ltd, Dept Zool, Oxford OX1 3PS, England. [Elyazar, Iqbal R. F.] Eijkman Oxford Clin Res Unit, Jakarta, Indonesia. [Teng, Hwa-Jen] Ctr Dis Control, Ctr Res Diagnost & Vaccine Dev, Taipei, Taiwan. RP Hay, SI (reprint author), Univ Oxford, Dept Zool, Spatial Ecol & Epidemiol Grp, South Pk Rd, Oxford OX1 3PS, England. EM simon.i.hay@gmail.com OI Hay, Simon/0000-0002-0611-7272; Brady, Oliver/0000-0002-3235-2129 FU German Academic Exchange Service (DAAD); Bill and Melinda Gates Foundation; BBSRC studentship; International Research Consortium on Dengue Risk Assessment Management and Surveillance (IDAMS, European Commission 7th Framework Programme) [21803]; Wellcome Trust [B9RZGS0, 095066]; ECDC [ECDC/09/018]; RAPIDD program of the Science & Technology Directorate, Department of Homeland Security; Fogarty International Center, National Institutes of Health; Rhodes Trust FX M.U.G.K. is funded by the German Academic Exchange Service (DAAD) through a graduate scholarship. M.E.S. is funded by a project grant from the Bill and Melinda Gates Foundation via the VecNet consortium (http://vecnet.org). O.J.B. is funded by a BBSRC studentship. J.P.M. and G.R.W.W. are funded by the International Research Consortium on Dengue Risk Assessment Management and Surveillance (IDAMS, European Commission 7th Framework Programme (21803), http:www.idams.eu, Publication #28). I.R.F.E. is funded by the Wellcome Trust (#B9RZGS0). VBORNET is an ECDC funded project (contract number ECDC/09/018). S.I.H. is funded by a Senior Research Fellowship from the Wellcome Trust (#095066) which also supports A.M. and K.A.D. S.I.H. and C.M.D. also acknowledge funding support from the RAPIDD program of the Science & Technology Directorate, Department of Homeland Security, and the Fogarty International Center, National Institutes of Health. FMS is funded by the Rhodes Trust. NR 31 TC 8 Z9 8 U1 1 U2 5 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 2052-4463 J9 SCI DATA JI Sci. Data PY 2015 VL 2 AR 150035 DI 10.1038/sdata.2015.35 PG 8 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA V45VM UT WOS:000209844100032 PM 26175912 ER PT J AU Messina, JP Pigott, DM Duda, KA Brownstein, JS Myers, MF George, DB Hay, SI AF Messina, Jane P. Pigott, David M. Duda, Kirsten A. Brownstein, John S. Myers, Monica F. George, Dylan B. Hay, Simon I. TI A global compendium of human Crimean-Congo haemorrhagic fever virus occurrence SO SCIENTIFIC DATA LA English DT Article AB In order to map global disease risk, a geographic database of human Crimean-Congo haemorrhagic fever virus (CCHFV) occurrence was produced by surveying peer-reviewed literature and case reports, as well as informal online sources. Here we present this database, comprising occurrence data linked to geographic point or polygon locations dating from 1953 to 2013. We fully describe all data collection, geo-positioning, database management and quality-control procedures. This is the most comprehensive database of confirmed CCHF occurrence in humans to-date, containing 1,721 geo-positioned occurrences in total. C1 [Messina, Jane P.; Pigott, David M.; Duda, Kirsten A.; Myers, Monica F.; George, Dylan B.; Hay, Simon I.] Univ Oxford, Dept Zool, Spatial Ecol & Epidemiol Grp, South Parks Rd, Oxford OX1 3PS, England. [Brownstein, John S.] Harvard Med Sch, Dept Pediat, Boston, MA 02115 USA. [Brownstein, John S.] Boston Childrens Hosp, Childrens Hosp, Informat Program, Boston, MA 02115 USA. [Hay, Simon I.] NIH, Fogarty Int Ctr, Bethesda, MD 20892 USA. RP Messina, JP (reprint author), Univ Oxford, Dept Zool, Spatial Ecol & Epidemiol Grp, South Parks Rd, Oxford OX1 3PS, England. EM jane.messina@zoo.ox.ac.uk OI Hay, Simon/0000-0002-0611-7272 FU Wellcome Trust [095066]; International Research Consortium on Dengue Risk Assessment Management and Surveillance (IDAMS) [21803]; Sir Richard Southwood Graduate Scholarship from the Department of Zoology at the University of Oxford; NIH National Library of Medicine [R01LM010812]; Bill & Melinda Gates Foundation [OPP1093011]; RAPIDD program of the Science & Technology Directorate, Department of Homeland Security; Fogarty International Center, National Institutes of Health FX S.I.H. is funded by a Senior Research Fellowship from the Wellcome Trust (095066), which also funds K.A.D. J.P.M. is funded by the International Research Consortium on Dengue Risk Assessment Management and Surveillance (IDAMS, 21803, http://www.idams.eu). D.M.P. is funded by a Sir Richard Southwood Graduate Scholarship from the Department of Zoology at the University of Oxford. JSB acknowledges funding from NIH National Library of Medicine (R01LM010812) and from the Bill & Melinda Gates Foundation (#OPP1093011). S.I.H. also acknowledges funding support from the RAPIDD program of the Science & Technology Directorate, Department of Homeland Security, and the Fogarty International Center, National Institutes of Health. NR 5 TC 1 Z9 1 U1 1 U2 2 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 2052-4463 J9 SCI DATA JI Sci. Data PY 2015 VL 2 AR 150016 DI 10.1038/sdata.2015.16 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA V45VM UT WOS:000209844100011 PM 25977820 ER PT J AU Sorichetta, A Hornby, GM Stevens, FR Gaughan, AE Linard, C Tatem, AJ AF Sorichetta, Alessandro Hornby, Graeme M. Stevens, Forrest R. Gaughan, Andrea E. Linard, Catherine Tatem, Andrew J. TI High-resolution gridded population datasets for Latin America and the Caribbean in 2010, 2015, and 2020 SO SCIENTIFIC DATA LA English DT Article AB The Latin America and the Caribbean region is one of the most urbanized regions in the world, with a total population of around 630 million that is expected to increase by 25% by 2050. In this context, detailed and contemporary datasets accurately describing the distribution of residential population in the region are required for measuring the impacts of population growth, monitoring changes, supporting environmental and health applications, and planning interventions. To support these needs, an open access archive of high- resolution gridded population datasets was created through disaggregation of the most recent official population count data available for 28 countries located in the region. These datasets are described here along with the approach and methods used to create and validate them. For each country, population distribution datasets, having a resolution of 3 arc seconds (approximately 100 m at the equator), were produced for the population count year, as well as for 2010, 2015, and 2020. All these products are available both through the WorldPop Project website and the WorldPop Dataverse Repository. C1 [Sorichetta, Alessandro; Tatem, Andrew J.] Univ Southampton, Geog & Environm, Highfield Campus, Southampton SO17 1BJ, Hants, England. [Sorichetta, Alessandro] Univ Southampton, Inst Life Sci, Southampton SO17 1BJ, Hants, England. [Hornby, Graeme M.] Univ Southampton, GeoData, Southampton SO17 1BJ, Hants, England. [Stevens, Forrest R.; Gaughan, Andrea E.] Univ Louisville, Dept Geog & Geosci, Louisville, KY 40292 USA. [Linard, Catherine] Univ Libre Bruxelles, Lutte Biol & Ecol Spatiale LUBIES, B-1050 Brussels, Belgium. [Linard, Catherine] Fonds Natl Rech Sci, B-1000 Brussels, Belgium. [Tatem, Andrew J.] NIH, Fogarty Int Ctr, Bethesda, MD 20892 USA. [Tatem, Andrew J.] Flowminder Fdn, SE-11355 Stockholm, Sweden. RP Sorichetta, A (reprint author), Univ Southampton, Geog & Environm, Highfield Campus, Southampton SO17 1BJ, Hants, England. EM A.Sorichetta@soton.ac.uk OI Stevens, Forrest/0000-0002-9328-3753 FU Bill & Melinda Gates Foundation [OPP1106427, 1032350]; NIH/NIAID [U19AI089674]; RAPIDD program of the Science and Technology Directorate; Department of Homeland Security; Fogarty International Center, National Institutes of Health FX A.S. is supported by funding from the Bill & Melinda Gates Foundation (OPP1106427, 1032350). A.J.T. is supported by funding from NIH/NIAID (U19AI089674), the Bill & Melinda Gates Foundation (OPP1106427, 1032350), and the RAPIDD program of the Science and Technology Directorate, Department of Homeland Security, and the Fogarty International Center, National Institutes of Health. This work forms part of the WorldPop Project (www.worldpop.org). The funders had no role in study design, data collection and analysis, decision to publish, and preparation of the manuscript. NR 65 TC 2 Z9 2 U1 1 U2 1 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 2052-4463 J9 SCI DATA JI Sci. Data PY 2015 VL 2 AR 150045 DI 10.1038/sdata.2015.45 PG 12 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA V45VM UT WOS:000209844100043 ER PT S AU Temprine, K York, AG Shroff, H AF Temprine, Kelsey York, Andrew G. Shroff, Hari BE Verveer, PJ TI Three-Dimensional Photoactivated Localization Microscopy with Genetically Expressed Probes SO ADVANCED FLUORESCENCE MICROSCOPY: METHODS AND PROTOCOLS SE Methods in Molecular Biology LA English DT Article; Book Chapter DE Super resolution; Single-molecule imaging; 3D microscopy; Cell biology ID OPTICAL RECONSTRUCTION MICROSCOPY; FLUORESCENCE MICROSCOPY; DIFFRACTION-LIMIT; RESOLUTION; PROTEINS; STORM AB Photoactivated localization microscopy (PALM) and related single-molecule imaging techniques enable biological image acquisition at similar to 20 nm lateral and similar to 50-100 nm axial resolution. Although such techniques were originally demonstrated on single imaging planes close to the coverslip surface, recent technical developments now enable the 3D imaging of whole fixed cells. We describe methods for converting a 2D PALM into a system capable of acquiring such 3D images, with a particular emphasis on instrumentation that is compatible with choosing relatively dim, genetically expressed photoactivatable fluorescent proteins (PA-FPs) as PALM probes. After reviewing the basics of 2D PALM, we detail astigmatic and multiphoton imaging approaches well suited to working with PA-FPs. We also discuss the use of open-source localization software appropriate for 3D PALM. C1 [Temprine, Kelsey; York, Andrew G.; Shroff, Hari] Natl Inst Biomed & Bioengn, Sect High Resolut Opt Imaging, NIH, Bethesda, MD 20892 USA. RP Temprine, K (reprint author), Natl Inst Biomed & Bioengn, Sect High Resolut Opt Imaging, NIH, Bethesda, MD 20892 USA. RI Shroff, Hari/E-7247-2016 OI Shroff, Hari/0000-0003-3613-8215 FU Intramural NIH HHS [, ZIA EB000074-03] NR 24 TC 0 Z9 0 U1 1 U2 11 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DR, STE 208, TOTOWA, NJ 07512-1165 USA SN 1064-3745 BN 978-1-4939-2080-8; 978-1-4939-2079-2 J9 METHODS MOL BIOL JI Methods Mol. Biol. PY 2015 VL 1251 BP 231 EP 261 DI 10.1007/978-1-4939-2080-8_13 D2 10.1007/978-1-4939-2080-8 PG 31 WC Biochemical Research Methods; Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA BB7SD UT WOS:000345967400014 PM 25391803 ER PT J AU Park, JS Kim, SH Kim, K Jin, CH Choi, KY Jang, J Choi, Y Gwon, AR Baik, SH Yun, UJ Chae, SY Lee, S Kang, YM Lee, KC Arumugam, TV Mattson, MP Park, JH Jo, DG AF Park, Jong-Sung Kim, Seol-Hee Kim, Kwangmeyung Jin, Cheng-Hao Choi, Ki Young Jang, Jiyeon Choi, Yuri Gwon, A-Ryeong Baik, Sang-Ha Yun, Ui Jeong Chae, Su Young Lee, Seulki Kang, Young Mo Lee, Kang Choon Arumugam, Thiruma V. Mattson, Mark P. Park, Jae Hyung Jo, Dong-Gyu TI Inhibition of Notch signalling ameliorates experimental inflammatory arthritis SO ANNALS OF THE RHEUMATIC DISEASES LA English DT Article ID NF-KAPPA-B; COLLAGEN-INDUCED ARTHRITIS; RHEUMATOID-ARTHRITIS; IN-VIVO; SYNOVIAL FIBROBLASTS; ENDOTHELIAL-CELLS; ISCHEMIC-STROKE; ANGIOGENESIS; EXPRESSION; NANOPARTICLES AB Objective To test the hypothesis that Notch signalling plays a role in the pathogenesis of rheumatoid arthritis (RA) and to determine whether pharmacological inhibition of Notch signalling with gamma-secretase inhibitors can ameliorate the RA disease process in an animal model. Methods Collagen-induced arthritis was induced in C57BL/6 or Notch antisense transgenic mice by immunisation with chicken type II collagen (CII). C57BL/6 mice were administered with different doses of inhibitors of gamma-secretase, an enzyme required for Notch activation, at disease onset or after onset of symptoms. Severity of arthritis was monitored by clinical and histological scores, and in vivo non-invasive near-infrared fluorescence (NIRF) images. Micro-CT was used to confirm joint destruction. The levels of CII antibodies and cytokines in serum were determined by ELISA and bead-based cytokine assay. The expression levels of cytokines were studied by quantitative PCR in rheumatoid synovial fibroblasts. Results The data show that Notch signalling stimulates synoviocytes and accelerates their production of proinflammatory cytokines and immune responses involving the upregulation of IgG1 and IgG2a. Pharmacological inhibition of gamma-secretase and antisense-mediated knockdown of Notch attenuates the severity of inflammatory arthritis, including arthritis indices, paw thickness, tissue damage and neutrophil infiltration, and reduces the levels of active NF-kappa B, ICAM-1, proinflammatory cytokines and matrix metalloproteinase-3 activity in the mouse model of RA. Conclusions These results suggest that Notch is involved in the pathogenesis of RA and that inhibition of Notch signalling is a novel approach for treating RA. C1 [Park, Jong-Sung; Kim, Seol-Hee; Jang, Jiyeon; Choi, Yuri; Gwon, A-Ryeong; Baik, Sang-Ha; Yun, Ui Jeong; Chae, Su Young; Lee, Kang Choon; Arumugam, Thiruma V.; Jo, Dong-Gyu] Sungkyunkwan Univ, Sch Pharm, Suwon 440746, South Korea. [Kim, Seol-Hee; Park, Jae Hyung] Sungkyunkwan Univ, Dept Polymer Sci, Suwon 440746, South Korea. [Kim, Seol-Hee; Park, Jae Hyung] Sungkyunkwan Univ, Dept Chem Engn, Suwon 440746, South Korea. [Kim, Kwangmeyung] Korea Inst Sci & Technol, Biomed Res Ctr, Seoul, South Korea. [Jin, Cheng-Hao] Heilongjiang Bayi Agr Univ, Coll Life Sci & Technol, Dept Biochem & Mol Biol, Daqing, Peoples R China. [Choi, Ki Young] Natl Inst Biomed Imaging & Bioengn, Lab Mol Imaging & Nanomed, NIH, Bethesda, MD USA. [Lee, Seulki] Johns Hopkins Univ, Wilmer Eye Inst, Russell H Morgan Dept Radiol & Radiol Sci, Ctr Canc Nanotechnol Excellence,Ctr Nanomed, Baltimore, MD 21218 USA. [Kang, Young Mo] Kyungpook Natl Univ, Sch Med, Dept Internal Med Rheumatol, Taegu, South Korea. [Arumugam, Thiruma V.] Natl Univ Singapore, Yong Loo Lin Sch Med, Dept Physiol, Singapore 117595, Singapore. [Mattson, Mark P.] NIA, Neurosci Lab, Intramural Res Program, Baltimore, MD 21224 USA. [Mattson, Mark P.] Johns Hopkins Univ, Sch Med, Dept Neurosci, Baltimore, MD 21205 USA. RP Jo, DG (reprint author), Sungkyunkwan Univ, Sch Pharm, 300 Cheoncheon Dong, Suwon 440746, South Korea. EM jhpark1@skku.edu; jodg@skku.edu RI Arumugam, Thiruma/B-4898-2011; CHOI, KI YOUNG/Q-7177-2016 FU Korea Healthcare Technology RD project [A092042]; National Research Foundation of Korean Government [2012-0009851, 2012R1A2A2A01047551, 2012R1A1A2009093] FX The Korea Healthcare Technology R&D project (A092042) and National Research Foundation of Korean Government (2012-0009851, 2012R1A2A2A01047551, 2012R1A1A2009093). NR 49 TC 12 Z9 12 U1 1 U2 13 PU BMJ PUBLISHING GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 0003-4967 EI 1468-2060 J9 ANN RHEUM DIS JI Ann. Rheum. Dis. PD JAN PY 2015 VL 74 IS 1 BP 267 EP 274 DI 10.1136/annrheumdis-2013-203467 PG 8 WC Rheumatology SC Rheumatology GA AU9XT UT WOS:000345945700049 PM 24255545 ER PT J AU Kelly, CM Northey, T Ryan, K Brooks, BR Kholkin, AL Rodriguez, BJ Buchete, NV AF Kelly, Catherine M. Northey, Thomas Ryan, Kate Brooks, Bernard R. Kholkin, Andrei L. Rodriguez, Brian J. Buchete, Nicolae-Viorel TI Conformational dynamics and aggregation behavior of piezoelectric diphenylalanine peptides in an external electric field SO BIOPHYSICAL CHEMISTRY LA English DT Article DE Diphenylalanine peptide; Piezoelectric peptide; Atomistic molecular dynamics; External electric field; Peptide-peptide interaction; Peptide aggregate ID MOLECULAR-DYNAMICS; BUILDING-BLOCKS; LIPID-MEMBRANES; FORCE-FIELDS; NANOTUBES; DIELECTROPHORESIS; FIBRILS; MANIPULATION; SIMULATIONS; POTENTIALS AB Aromatic peptides including diphenylalanine (FF) have the capacity to self-assemble into ordered, biocompatible nanostructures with piezoelectric properties relevant to a variety of biomedical applications. Electric fields are commonly applied to align FF nanotubes, yet little is known about the effect of the electric field on the assembly process. Using all-atom molecular dynamics with explicit water molecules, we examine the response of FF monomers to the application of a constant external electric field over a range of intensities. We probe the aggregation mechanism of FF peptides, and find that the presence of even relatively weak fields can accelerate ordered aggregation, primarily by facilitating the alignment of individual molecular dipole moments. This is modulated by the conformational response of individual FF peptides (e.g., backbone stretching) and by the cooperative alignment of neighboring FF and water molecules. These observations may facilitate future studies on the controlled formation of nanostructured aggregates of piezoelectric peptides and the understanding of their electro-mechanical properties. (C) 2014 Elsevier B.V. All rights reserved. C1 [Kelly, Catherine M.; Northey, Thomas; Ryan, Kate; Rodriguez, Brian J.; Buchete, Nicolae-Viorel] Univ Coll Dublin, Sch Phys, Dublin 4, Ireland. [Kelly, Catherine M.; Northey, Thomas; Buchete, Nicolae-Viorel] Univ Coll Dublin, Complex & Adapt Syst Lab, Dublin 4, Ireland. [Ryan, Kate; Rodriguez, Brian J.] Univ Coll Dublin, Conway Inst Biomol & Biomed Res, Dublin 4, Ireland. [Brooks, Bernard R.] NHLBI, Lab Computat Biol, NIH, Bethesda, MD 20892 USA. [Kholkin, Andrei L.] Univ Aveiro, Dept Mat & Ceram Engn, Aveiro, Portugal. [Kholkin, Andrei L.] Univ Aveiro, CICECO, Aveiro, Portugal. RP Buchete, NV (reprint author), Univ Coll Dublin, Sch Phys, Dublin 4, Ireland. EM buchete@ucd.ie RI Buchete, Nicolae-Viorel/C-6200-2015; Kholkin, Andrei/G-5834-2010; Kelly, Catherine/D-6267-2014 OI Buchete, Nicolae-Viorel/0000-0001-9861-1157; Kholkin, Andrei/0000-0003-3432-7610; Kelly, Catherine/0000-0002-9408-7463 FU University College Dublin Structured Ph.D. Programme in Simulation Science; European Regional Development Fund (ERDF); European Commission within FP7 Marie Curie Initial Training Network "Nanomotion" [290158]; DJEI/DES/SFI/HEA Irish Centre for High-End Computing (ICHEC); Biowulf Linux cluster at the National Institutes of Health, USA FX This work was supported by the University College Dublin Structured Ph.D. Programme in Simulation Science, funded under the Programme for Research in Third Level Institutions (PRTLI) Cycle 5 which is co-funded by the European Regional Development Fund (ERDF), and also by the European Commission within FP7 Marie Curie Initial Training Network "Nanomotion" (grant agreement number 290158).; The authors thank the DJEI/DES/SFI/HEA Irish Centre for High-End Computing (ICHEC) and the Biowulf Linux cluster at the National Institutes of Health, USA (http://biowulf.nih.gov) for the provision of computational facilities and support. NR 46 TC 12 Z9 12 U1 5 U2 46 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0301-4622 EI 1873-4200 J9 BIOPHYS CHEM JI Biophys. Chem. PD JAN PY 2015 VL 196 BP 16 EP 24 DI 10.1016/j.bpc.2014.08.009 PG 9 WC Biochemistry & Molecular Biology; Biophysics; Chemistry, Physical SC Biochemistry & Molecular Biology; Biophysics; Chemistry GA AU6QP UT WOS:000345727400003 PM 25240398 ER PT J AU Simonetti, FR Kearney, MF AF Simonetti, Francesco R. Kearney, Mary F. TI Review: influence of ART on HIV genetics SO CURRENT OPINION IN HIV AND AIDS LA English DT Review DE antiretroviral therapy; HIV diversity; HIV early infection; HIV genetics; HIV replication ID IMMUNODEFICIENCY-VIRUS TYPE-1; SUPPRESSIVE ANTIRETROVIRAL THERAPY; FEMALE GENITAL-TRACT; LOW-LEVEL VIREMIA; T-CELL COUNTS; INFECTED-CELLS; PERIPHERAL-BLOOD; VIRAL RESERVOIR; COMPARTMENTALIZATION; PROLIFERATION AB Purpose of review HIV genetic diversity poses major challenges for the prevention, control, and cure of infection. Characterizing the diversity and evolution of HIV populations within the host provides insights into the mechanisms of HIV persistence during antiretroviral therapy (ART). This review describes the HIV diversity within patients, how it is affected by suppressive ART, and makes a case for early treatment after HIV infection. Recent findings HIV evolution is effectively halted by ART. However, cells that were infected prior to initiating therapy can proliferate to very high numbers both before and during treatment. Such clonal expansions result in the persistence of integrated proviruses despite therapy. These expanding proviruses have been shown to be a source for residual viremia during ART, and they may be a source for viral rebound after interrupting ART. Summary Plasma HIV RNA shows no evidence for evolution during ART, suggesting that HIV persistence is not driven by low-level, ongoing replication. The emergence of identical viral sequences observed in both HIV RNA and DNA is likely due to proliferation of infected cells. Early treatment restricts the viral population and reduces the number of variants that must be targeted for future therapeutic strategies. C1 [Simonetti, Francesco R.; Kearney, Mary F.] NCI, HIV Drug Resistance Program, Frederick, MD 21702 USA. [Simonetti, Francesco R.] L Sacco, Dept Biomed & Clin Sci, Milan, Italy. RP Kearney, MF (reprint author), NCI, HIV Drug Resistance Program, 1050 Boyles St,Bldg 535,Room 109, Frederick, MD 21702 USA. EM kearneym@ncifcrf.gov FU NIH; NIH Bench-to-Bedside grants FX The laboratories of F.R.S. and M.F.K. are funded by intramural NIH funding and NIH Bench-to-Bedside grants. NR 55 TC 2 Z9 2 U1 3 U2 17 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1746-630X EI 1746-6318 J9 CURR OPIN HIV AIDS JI Curr. Opin. HIV AIDS PD JAN PY 2015 VL 10 IS 1 BP 49 EP 54 DI 10.1097/COH.0000000000000120 PG 6 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA AU9TY UT WOS:000345938600008 PM 25389802 ER PT J AU Kim, JC Duverger, O Hwang, J Morasso, MI AF Kim, Jin-Chul Duverger, Olivier Hwang, Joonsung Morasso, Maria I. TI Epidermal Stem Cells in the Isthmus/Infundibulum Influence Hair Shaft Differentiation: Evidence from Targeted DLX3 Deletion SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Letter ID FOLLICLE; POPULATIONS C1 [Kim, Jin-Chul; Duverger, Olivier; Hwang, Joonsung; Morasso, Maria I.] NIAMSD, Skin Biol Lab, NIH, Bethesda, MD 20892 USA. RP Kim, JC (reprint author), NIAMSD, Skin Biol Lab, NIH, Bethesda, MD 20892 USA. EM morasso@nih.gov FU Intramural NIH HHS [ZIA AR041171-06] NR 12 TC 0 Z9 0 U1 1 U2 4 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0022-202X EI 1523-1747 J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD JAN PY 2015 VL 135 IS 1 BP 299 EP 301 DI 10.1038/jid.2014.287 PG 3 WC Dermatology SC Dermatology GA AW4AX UT WOS:000346225000036 PM 25120002 ER PT J AU Mehta, NN Dagur, PK Rose, SM Naik, HB Stansky, E Doveikis, J Biancotto, A Playford, MP McCoy, JP AF Mehta, Nehal N. Dagur, Pradeep K. Rose, Shawn M. Naik, Haley B. Stansky, Elena Doveikis, Julia Biancotto, Angelique Playford, Martin P. McCoy, J. Philip, Jr. TI IL-17A Production in Human Psoriatic Blood and Lesions by CD146+T Cells SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Letter ID PERIPHERAL-BLOOD; LYMPHOCYTES; DISEASES; PROMOTES C1 [Mehta, Nehal N.; Rose, Shawn M.; Doveikis, Julia; Playford, Martin P.] NHLBI, Sect Inflammat & Cardiometabol Dis, Bethesda, MD 20892 USA. [Dagur, Pradeep K.; Stansky, Elena; McCoy, J. Philip, Jr.] NHLBI, Bethesda, MD 20892 USA. [Rose, Shawn M.] Natl Inst Arthrit & Musculoskeletal & Skin Dis NI, Bethesda, MD USA. [Naik, Haley B.] NCI, NIH, Bethesda, MD 20892 USA. [Biancotto, Angelique; McCoy, J. Philip, Jr.] Ctr Human Immunol Autoimmun & Inflammat, Bethesda, MD USA. RP Mehta, NN (reprint author), NHLBI, Sect Inflammat & Cardiometabol Dis, Bldg 10, Bethesda, MD 20892 USA. EM nehal.mehta@nih.gov FU Intramural NIH HHS [ZIC HL005905-06] NR 9 TC 5 Z9 5 U1 0 U2 3 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0022-202X EI 1523-1747 J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD JAN PY 2015 VL 135 IS 1 BP 311 EP 314 DI 10.1038/jid.2014.317 PG 4 WC Dermatology SC Dermatology GA AW4AX UT WOS:000346225000040 PM 25058615 ER PT J AU Kenton, K Stoddard, AM Zyczynski, H Albo, M Rickey, L Norton, P Wai, C Kraus, SR Sirls, LT Kusek, JW Litman, HJ Chang, RP Richter, HE AF Kenton, Kimberly Stoddard, Anne M. Zyczynski, Halina Albo, Michael Rickey, Leslie Norton, Peggy Wai, Clifford Kraus, Stephen R. Sirls, Larry T. Kusek, John W. Litman, Heather J. Chang, Robert P. Richter, Holly E. TI 5-Year Longitudinal Followup after Retropubic and Transobturator Mid Urethral Slings SO JOURNAL OF UROLOGY LA English DT Article DE urinary incontinence, stress; suburethral slings ID STRESS URINARY-INCONTINENCE; FREE VAGINAL TAPE; SURGERY; COLPOSUSPENSION; QUESTIONNAIRE; SATISFACTION; WOMEN AB Purpose: Few studies have characterized longer-term outcomes after retropubic and transobturator mid urethral slings. Materials and Methods: Women completing 2-year participation in a randomized equivalence trial who had not undergone surgical re-treatment for stress urinary incontinence were invited to participate in a 5-year observational cohort. The primary outcome, treatment success, was defined as no re-treatment or self-reported stress incontinence symptoms. Secondary outcomes included urinary symptoms and quality of life, satisfaction, sexual function and adverse events. Results: Of 597 women 404 (68%) from the original trial enrolled in the study. Five years after surgical treatment success was 7.9% greater in women assigned to the retropubic sling compared to the transobturator sling (51.3% vs 43.4%, 95% CI = 1.4, 17.2), not meeting prespecified criteria for equivalence. Satisfaction decreased during 5 years but remained high and similar between arms (retropubic sling 79% vs transobturator sling 85%, p = 0.15). Urinary symptoms and quality of life worsened with time (p < 0.001), and women with a retropubic sling reported greater urinary urgency (p = 0.001), more negative impact on quality of life (p = 0.02) and worse sexual function (p = 0.001). There was no difference in the proportion of women experiencing at least 1 adverse event (p = 0.17). Seven new mesh erosions were noted (retropubic sling 3, transobturator sling 4). Conclusions: Treatment success decreased during 5 years for retropubic and transobturator slings, and did not meet the prespecified criteria for equivalence with retropubic demonstrating a slight benefit. However, satisfaction remained high in both arms. Women undergoing a transobturator sling procedure reported more sustained improvement in urinary symptoms and sexual function. New mesh erosions occurred in both arms over time, although at a similarly low rate. C1 [Kenton, Kimberly] Northwestern Univ, Chicago, IL 60611 USA. [Stoddard, Anne M.; Chang, Robert P.] New England Res Inst, Watertown, MA 02172 USA. [Litman, Heather J.] Boston Childrens Hosp, Boston, MA USA. [Zyczynski, Halina] Univ Pittsburgh, Magee Womens Res Inst, Pittsburgh, PA USA. [Albo, Michael] Univ Calif San Diego, San Diego, CA 92103 USA. [Rickey, Leslie] Yale Univ, New Haven, CT USA. [Norton, Peggy] Univ Utah, Salt Lake City, UT USA. [Wai, Clifford] Univ Texas SW Med Ctr Dallas, Dallas, TX 75390 USA. [Kraus, Stephen R.] Univ Texas Hlth Sci Ctr San Antonio, San Antonio, TX 78229 USA. [Sirls, Larry T.] William Beaumont Hosp, Royal Oak, MI 48072 USA. [Kusek, John W.] NIDDK, Bethesda, MD USA. [Richter, Holly E.] Univ Alabama Birmingham, Birmingham, AL USA. Urinary Incontinence Treatment Network, Salt Lake City, UT USA. RP Kenton, K (reprint author), Northwestern Univ, Prentice Womens Hosp, Feinberg Sch Med, Chicago, IL 60611 USA. EM kimberly.kenton@northwestern.edu FU NIH NIDDK [1U10 DK60379-01] FX Supported by NIH NIDDK 1U10 DK60379-01. NR 23 TC 17 Z9 17 U1 1 U2 3 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0022-5347 EI 1527-3792 J9 J UROLOGY JI J. Urol. PD JAN PY 2015 VL 193 IS 1 BP 203 EP 210 DI 10.1016/j.juro.2014.08.089 PG 8 WC Urology & Nephrology SC Urology & Nephrology GA AW3FL UT WOS:000346171500053 PM 25158274 ER PT J AU Fwu, CW Kirkali, Z McVary, KT Burrows, PK Eggers, PW Kusek, JW AF Fwu, Chyng-Wen Kirkali, Ziya McVary, Kevin T. Burrows, Pamela K. Eggers, Paul W. Kusek, John W. TI Cross-Sectional and Longitudinal Associations of Sexual Function with Lower Urinary Tract Symptoms in Men with Benign Prostatic Hyperplasia SO JOURNAL OF UROLOGY LA English DT Article DE prostatic hyperplasia; lower urinary tract symptoms; sexual dysfunction, physiological ID MODIFIABLE RISK-FACTORS; ERECTILE DYSFUNCTION; EJACULATORY DYSFUNCTION; DOUBLE-BLIND; FINASTERIDE; TRIAL; PROGRESSION; THERAPY AB Purpose: We examine the cross-sectional associations between baseline characteristics and sexual function and the longitudinal associations between change in lower urinary tract symptoms and change in sexual function among men with benign prostatic hyperplasia. Materials and Methods: We studied lower urinary tract symptoms assessed by the AUA-SI and sexual function determined by the BMSFI in men enrolled in the MTOPS study. The cross-sectional cohort included 2,916 men who completed the BMSFI at baseline. The longitudinal cohort included 672 men who were randomized to placebo and had completed the BMSFI at baseline and at least once during a 4-year followup. Multiple adjusted linear modeling for each domain of the BMSFI was performed to assess associations of sexual function with lower urinary tract symptoms. Results: After adjustment for baseline demographic and clinical characteristics, increased age, less education, obesity and severe lower urinary tract symptoms were each significantly associated with poorer sexual drive, erectile function, ejaculatory function, sexual problem assessment and overall satisfaction in the cross-sectional cohort. However, none of these baseline characteristics predicted change in sexual function in the longitudinal cohort. Decline in sexual function in all sexual function domains associated with worsening of lower urinary tract symptoms in this group was small. Conclusions: Increased age, less education, obesity and more severe lower urinary tract symptoms were individually associated cross-sectionally, but not longitudinally, with poorer sexual function in men with lower urinary tract symptoms/benign prostatic hyperplasia. The decline in sexual function associated with worsening of lower urinary tract symptoms in men assigned to placebo was small. C1 [Fwu, Chyng-Wen] Social & Sci Syst Inc, Silver Spring, MD 20910 USA. [Kirkali, Ziya; Eggers, Paul W.; Kusek, John W.] NIDDK, Div Kidney Urol & Hematol Dis, NIH, Bethesda, MD 20892 USA. [Burrows, Pamela K.] George Washington Univ, Ctr Biostat, Rockville, MD USA. [McVary, Kevin T.] So Illinois Univ, Sch Med, Div Urol, Springfield, IL USA. RP Fwu, CW (reprint author), Social & Sci Syst Inc, 8757 Georgia Ave,12th Floor, Silver Spring, MD 20910 USA. EM cfwu@s-3.com FU National Institute of Diabetes and Digestive and Kidney Diseases [HHSN 276201200161U] FX Supported by a contract from the National Institute of Diabetes and Digestive and Kidney Diseases (HHSN 276201200161U). NR 30 TC 4 Z9 4 U1 0 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0022-5347 EI 1527-3792 J9 J UROLOGY JI J. Urol. PD JAN PY 2015 VL 193 IS 1 BP 231 EP 238 DI 10.1016/j.juro.2014.08.086 PG 8 WC Urology & Nephrology SC Urology & Nephrology GA AW3FL UT WOS:000346171500067 PM 25150638 ER PT J AU McBain, CJ Kittler, J Luscher, B Mody, I Orser, BA AF McBain, Chris J. Kittler, Josef Luscher, Bernhard Mody, Istvan Orser, Beverley A. TI GABAergic Signaling in Health and Disease SO NEUROPHARMACOLOGY LA English DT Editorial Material C1 [McBain, Chris J.; Kittler, Josef; Luscher, Bernhard; Mody, Istvan; Orser, Beverley A.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Porter Neurosci Res Ctr, Bethesda, MD 20892 USA. RP McBain, CJ (reprint author), Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Porter Neurosci Res Ctr, Bldg 35,Room 3C-903,35 Convent Dr,MSC 3715, Bethesda, MD 20892 USA. EM mcbainc@mail.nih.gov RI Kittler, Josef/E-9113-2010; OI Kittler, Josef/0000-0002-3437-9456; Luscher, Bernhard/0000-0003-1375-1906 FU NIMH NIH HHS [R01 MH099851] NR 0 TC 1 Z9 1 U1 0 U2 9 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0028-3908 EI 1873-7064 J9 NEUROPHARMACOLOGY JI Neuropharmacology PD JAN PY 2015 VL 88 SI SI BP 1 EP 1 DI 10.1016/j.neuropharm.2014.10.001 PG 1 WC Neurosciences; Pharmacology & Pharmacy SC Neurosciences & Neurology; Pharmacology & Pharmacy GA AU9ZD UT WOS:000345949500001 PM 25305324 ER PT J AU Brown, HA Roth, G Holzapfel, G Shen, S Rahbari, K Ireland, J Zou, ZC Sun, PD AF Brown, Haley A. Roth, Gwynne Holzapfel, Genevieve Shen, Sarek Rahbari, Kate Ireland, Joanna Zou, Zhongcheng Sun, Peter D. TI Development of an improved mammalian overexpression method for human CD62L SO PROTEIN EXPRESSION AND PURIFICATION LA English DT Article DE Recombinant mammalian overexpression system; Glutamine synthetase-based expression system; Methionine sulfoximine (MSX); Recombinant CD62L; L-selectin; Stable CD62L-expression CHO cell lines ID CELL EXPRESSION SYSTEM; NODE HOMING RECEPTOR; SELECTIN; GENE AB We have previously developed a glutamine synthetase (GS)-based mammalian recombinant protein expression system that is capable of producing 5-30 mg/L recombinant proteins. The over expression is based on multiple rounds of target gene amplification driven by methionine sulfoximine (MSX), an inhibitor of glutamine synthetase. However, like other stable mammalian over expression systems, a major shortcoming of the GS-based expression system is its lengthy turn-around time, typically taking 4-6 months to produce. To shorten the construction time, we replaced the multi-round target gene amplifications with single-round in situ amplifications, thereby shortening the cell line construction to 2 months. The single-round in situ amplification method resulted in highest recombinant CD62L expressing CHO cell lines producing similar to 5 mg/L soluble CD62L, similar to those derived from the multi-round amplification and selection method. In addition, we developed a MSX resistance assay as an alternative to utilizing ELISA for evaluating the expression level of stable recombinant CHO cell lines. Published by Elsevier Inc. C1 [Brown, Haley A.; Roth, Gwynne; Holzapfel, Genevieve; Shen, Sarek; Rahbari, Kate; Ireland, Joanna; Zou, Zhongcheng; Sun, Peter D.] NIAID, Struct Immunol Sect, Immunogenet Lab, NIH, Rockville, MD 20852 USA. RP Sun, PD (reprint author), NIAID, Struct Immunol Sect, Immunogenet Lab, NIH, 12441 Parklawn Dr, Rockville, MD 20852 USA. EM psun@nih.gov FU Intramural Research Program of the National Institute of Allergy and Infectious Diseases, National Institutes of Health FX This research is supported by the Intramural Research Program of the National Institute of Allergy and Infectious Diseases, National Institutes of Health. NR 15 TC 0 Z9 0 U1 0 U2 1 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1046-5928 EI 1096-0279 J9 PROTEIN EXPRES PURIF JI Protein Expr. Purif. PD JAN PY 2015 VL 105 BP 8 EP 13 DI 10.1016/j.pep.2014.09.018 PG 6 WC Biochemical Research Methods; Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology GA AU8CB UT WOS:000345823100002 PM 25286402 ER PT J AU Holmgren, M Rosenthal, JJC AF Holmgren, Miguel Rosenthal, Joshua J. C. TI Regulation of Ion Channel and Transporter Function Through RNA Editing SO CURRENT ISSUES IN MOLECULAR BIOLOGY LA English DT Review ID CURRENT-VOLTAGE RELATIONSHIP; GLUTAMATE-OPERATED CHANNELS; SHAKER POTASSIUM CHANNELS; PIG VENTRICULAR MYOCYTES; RECEPTOR SUBUNITS GLUR5; DEPENDENT K+ CHANNELS; MEMBRANE FATTY-ACIDS; AUDITORY HAIR-CELLS; PRE-MESSENGER-RNAS; NA/K PUMP CURRENT AB A large proportion of the recoding events mediated by RNA editing are in mRNAs that encode ion channels and transporters. The effects of these events on protein function have been characterized in only a few cases. In even fewer instances are the mechanistic underpinnings of these effects understood. This review focuses on how RNA editing affects protein function and higher order physiology. In mammals, particular attention is given to the GluA2, an ionotropic glutamate receptor subunit, and K-v 1.1, a voltage-dependent K+ channel, because they are particularly well understood. In K-v addition, work on cephalopod K+ channels and Na+/K+-ATPases has also provided important clues on the rules used by RNA editing to regulate excitability. Finally, we discuss some of the emerging targets for editing and how this process may be used to regulate nervous function in response to a variable environment. C1 [Holmgren, Miguel] NINDS, Mol Neurophysiol Sect, Porter Neurosci Res Ctr, NIH, Bethesda, MD 20892 USA. [Rosenthal, Joshua J. C.] Univ Puerto Rico Med Sci, Inst Neurobiol, San Juan, PR USA. [Rosenthal, Joshua J. C.] Univ Puerto Rico Med Sci, Dept Biochem, San Juan, PR USA. RP Holmgren, M (reprint author), NINDS, Mol Neurophysiol Sect, Porter Neurosci Res Ctr, NIH, Bldg 36,Rm 4D04, Bethesda, MD 20892 USA. EM Holmgren@ninds.nih.gov; rosenthal.joshua@gmail.com FU Intramural NIH HHS [Z01 NS003019-01] NR 101 TC 2 Z9 2 U1 1 U2 22 PU HORIZON SCIENTIFIC PRESS PI POOLE PA UNIT 7570, PO BOX 7169, WAREHAM RD, POOLE BH15 9EL, ENGLAND SN 1467-3037 EI 1467-3045 J9 CURR ISSUES MOL BIOL JI Curr. Issues Mol. Biol. PY 2015 VL 17 BP 23 EP 36 PG 14 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA AU2CS UT WOS:000345424200003 PM 25347917 ER PT J AU Chen, SH Oyarzabal, EA Sung, YF Chu, CH Wang, QS Chen, SL Lu, RB Hong, JS AF Chen, Shih-Heng Oyarzabal, Esteban A. Sung, Yueh-Feng Chu, Chun-Hsien Wang, Qingshan Chen, Shiou-Lan Lu, Ru-Band Hong, Jau-Shyong TI Microglial Regulation of Immunological and Neuroprotective Functions of Astroglia SO GLIA LA English DT Article DE astroglia; microglia; glial cell line-derived neurotrophic factor; glial interaction; neuroinflammation; neuroprotection ID TUMOR-NECROSIS-FACTOR; NITRIC-OXIDE SYNTHASE; TOLL-LIKE RECEPTOR-4; TNF-ALPHA; DOPAMINERGIC-NEURONS; HUMAN ASTROCYTES; UP-REGULATION; NG2-POSITIVE CELLS; GENE-EXPRESSION; INNATE IMMUNITY AB Microglia and astroglia play critical roles in the development, function, and survival of neurons in the CNS. However, under inflammatory conditions the role of astrogliosis in the inflammatory process and its effects on neurons remains unclear. Here, we used several types of cell cultures treated with the bacterial inflammogen LPS to address these questions. We found that the presence of astroglia reduced inflammation-driven neurotoxicity, suggesting that astrogliosis is principally neuroprotective. Neutralization of supernatant glial cell line-derived neurotrophic factor (GDNF) released from astroglia significantly reduced this neuroprotective effect during inflammation. To determine the immunological role of astroglia, we optimized a highly-enriched astroglial culture protocol and demonstrated that LPS failed to induce the synthesis and release of TNF- and iNOS/NO. Instead we found significant enhancement of TNF- and iNOS expression in highly-enriched astroglial cultures required the presence of 0.5-1% microglia, respectively. Thus suggesting that microglial-astroglial interactions are required for LPS to induce the expression of pro-inflammatory factors and GDNF from astroglia. Specifically, we found that microglia-derived TNF- plays a pivotal role as a paracrine signal to regulate the neuroprotective functions of astrogliosis. Taken together, these findings suggest that astroglia may not possess the ability to directly recognize the innate immune stimuli LPS, but rather depend on crosstalk with microglia to elicit release of neurotrophic factors as a counterbalance to support neuronal survival from the collateral damage generated by activated microglia during neuroinflammation. GLIA 2015;63:118-131 Main Points Microglia modulate astroglial in response to neuroinflammation through paracrine signaling. Microglia driven astrogliosis during neuroinflammation is neuroprotective rather than neurotoxic C1 [Chen, Shih-Heng; Oyarzabal, Esteban A.; Sung, Yueh-Feng; Chu, Chun-Hsien; Wang, Qingshan; Hong, Jau-Shyong] NIEHS, Lab Toxicol & Pharmacol, NIH, Res Triangle Pk, NC 27709 USA. [Sung, Yueh-Feng] Natl Def Med Ctr, Triserv Gen Hosp, Dept Neurol, Taipei, Taiwan. [Chen, Shiou-Lan] Kaohsiung Med Univ, Sch Med, Dept Neurol, Kaohsiung, Taiwan. [Lu, Ru-Band] Natl Cheng Kung Univ, Inst Behav Med, Coll Med & Hosp, Tainan 70428, Taiwan. [Lu, Ru-Band] Natl Cheng Kung Univ, Dept Psychiat, Tainan 70428, Taiwan. RP Chen, SH (reprint author), NIEHS, NIH, 111 TW Alexander Dr, Res Triangle Pk, NC 27709 USA. EM chens3@niehs.nih.gov; rblu@mail.ncku.edu.tw OI Chen, Shih-Heng/0000-0002-5853-6903 FU National Institute of Environmental Health Sciences, NIH FX Grant sponsor: National Institute of Environmental Health Sciences, NIH. NR 77 TC 11 Z9 11 U1 1 U2 15 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0894-1491 EI 1098-1136 J9 GLIA JI Glia PD JAN PY 2015 VL 63 IS 1 BP 118 EP 131 DI 10.1002/glia.22738 PG 14 WC Neurosciences SC Neurosciences & Neurology GA AU0XC UT WOS:000345344500009 PM 25130274 ER PT J AU Cascio, CN Carp, J O'Donnell, MB Tinney, FJ Bingham, CR Shope, JT Ouimet, MC Pradhan, AK Simons-Morton, BG Falk, EB AF Cascio, Christopher N. Carp, Joshua O'Donnell, Matthew Brook Tinney, Francis J., Jr. Bingham, C. Raymond Shope, Jean T. Ouimet, Marie Claude Pradhan, Anuj K. Simons-Morton, Bruce G. Falk, Emily B. TI Buffering Social Influence: Neural Correlates of Response Inhibition Predict Driving Safety in the Presence of a Peer SO JOURNAL OF COGNITIVE NEUROSCIENCE LA English DT Article ID ADOLESCENT RISK-TAKING; DECISION-MAKING; TEENAGE DRIVERS; PROSOCIAL BEHAVIOR; BRAIN; PASSENGERS; CRASHES; SUSCEPTIBILITY; FRIENDSHIPS; REACTIVITY AB Adolescence is a period characterized by increased sensitivity to social cues, as well as increased risk-taking in the presence of peers. For example, automobile crashes are the leading cause of death for adolescents, and driving with peers increases the risk of a fatal crash. Growing evidence points to an interaction between neural systems implicated in cognitive control and social and emotional context in predicting adolescent risk. We tested such a relationship in recently licensed teen drivers. Participants completed an fMRI session in which neural activity was measured during a response inhibition task, followed by a separate driving simulator session 1 week later. Participants drove alone and with a peer who was randomly assigned to express risk-promoting or risk-averse social norms. The experimentally manipulated social context during the simulated drive moderated the relationship between individual differences in neural activity in the hypothesized cognitive control network (right inferior frontal gyrus, BG) and risk-taking in the driving context a week later. Increased activity in the response inhibition network was not associated with risk-taking in the presence of a risky peer but was significantly predictive of safer driving in the presence of a cautious peer, above and beyond self-reported susceptibility to peer pressure. Individual differences in recruitment of the response inhibition network may allow those with stronger inhibitory control to override risky tendencies when in the presence of cautious peers. This relationship between social context and individual differences in brain function expands our understanding of neural systems involved in top-down cognitive control during adolescent development. C1 [Cascio, Christopher N.; O'Donnell, Matthew Brook; Falk, Emily B.] Univ Penn, Philadelphia, PA 19104 USA. [Carp, Joshua; Tinney, Francis J., Jr.; Bingham, C. Raymond; Shope, Jean T.; Pradhan, Anuj K.] Univ Michigan, Ann Arbor, MI 48109 USA. [Ouimet, Marie Claude] Univ Sherbrooke, Sherbrooke, PQ J1K 2R1, Canada. [Simons-Morton, Bruce G.] NICHHD, Bethesda, MD USA. RP Cascio, CN (reprint author), Univ Penn, Annenberg Sch Commun, 3620 Walnut St, Philadelphia, PA 19104 USA. EM ccascio@asc.upenn.edu; falk@asc.upenn.edu OI Pradhan, Anuj/0000-0002-7612-4208; Simons-Morton, Bruce/0000-0003-1099-6617 FU Eunice Kennedy Shriver National Institute of Child Health and Human Development [HHSN275201000007C]; University of Michigan Injury Center Pilot Grant [1R21HD073549-01A1]; NIH/NICHD [IR21HD073549-01A1] FX The research was supported by (1) the intramural research program of the Eunice Kennedy Shriver National Institute of Child Health and Human Development Contract HHSN275201000007C (PI: Bingham), (2) University of Michigan Injury Center Pilot Grant 1R21HD073549-01A1 (PI: Falk), and (3) NIH/NICHD IR21HD073549-01A1 (PI: Falk). The authors gratefully acknowledge Nicholas Wasylyshyn, Andrew Suzuki, Robin Liu, Ryan Bondy, Matthew Sweet, and Cary Welsh, as well as Andrea I. Barretto, Jennifer LaRose, Farideh Almani, and Alyssa Templar, for research assistance and the staff of the University of Michigan fMRI Center. We also thank Sylvia Morelli, Elliot Berkman, Will Moore, and the Pfeifer lab for provision of anatomical regions of interest and Eva Telzer for helpful discussions of our results. Finally, the authors would like to thank the reviewers for their helpful feedback and suggestions. NR 63 TC 6 Z9 6 U1 4 U2 41 PU MIT PRESS PI CAMBRIDGE PA ONE ROGERS ST, CAMBRIDGE, MA 02142-1209 USA SN 0898-929X EI 1530-8898 J9 J COGNITIVE NEUROSCI JI J. Cogn. Neurosci. PD JAN PY 2015 VL 27 IS 1 BP 83 EP 95 DI 10.1162/jocn_a_00693 PG 13 WC Neurosciences; Psychology, Experimental SC Neurosciences & Neurology; Psychology GA AU4ZK UT WOS:000345616600008 PM 25100217 ER PT J AU Liang, ZF Liu, X Zhang, NY AF Liang, Zhifeng Liu, Xiao Zhang, Nanyin TI Dynamic resting state functional connectivity in awake and anesthetized rodents SO NEUROIMAGE LA English DT Article DE Resting-state functional connectivity; Dynamic; Rat; Medial prefrontal cortex; Somatosensory cortex ID DEFAULT-MODE NETWORK; TRAUMATIC BRAIN-INJURY; CINGULATE CORTEX; RAT-BRAIN; SPATIOTEMPORAL DYNAMICS; FMRI; FLUCTUATIONS; MRI; SIGNAL; ANTICORRELATIONS AB Since its introduction, resting-state functional magnetic resonance imaging (rsfMRI) has been a powerful tool for investigating functional neural networks in both normal and pathological conditions. When measuring resting-state functional connectivity (RSFC), most rsfMRI approaches do not consider its temporal variations and thus only provide the averaged RSFC over the scan time. Recently, there has been a surge of interest to investigate the dynamic characteristics of RSFC in humans, and promising results have been yielded. However, our knowledge regarding the dynamic RSFC in animals remains sparse. In the present study we utilized the single-volume co-activation method to systematically study the dynamic properties of RSFC within the networks of infralimbic cortex (IL) and primary somatosensory cortex (S1) in both awake and anesthetized rats. Our data showed that both IL and S1 networks could be decomposed into several spatially reproducible but temporally changing co-activation patterns (CAPs), suggesting that dynamic RSFC was indeed a characteristic feature in rodents. In addition, we demonstrated that anesthesia profoundly impacted the dynamic RSFC of neural circuits subserving cognitive and emotional functions but had less effects on sensorimotor systems. Finally, we examined the temporal characteristics of each CAP, and found that individual CAPs exhibited consistent temporal evolution patterns. Together, these results suggest that dynamic RSFC might be a general phenomenon in vertebrate animals. In addition, this study has paved the way for further understanding the alterations of dynamic RSFC in animal models of brain disorders. (C) 2014 Elsevier Inc. All rights reserved. C1 [Liang, Zhifeng; Zhang, Nanyin] Penn State Univ, Dept Biomed Engn, Huck Inst Life Sci, University Pk, PA 16802 USA. [Liu, Xiao] NINDS, Adv MRI Sect, Lab Funct & Mol Imaging, NIH, Bethesda, MD 20892 USA. RP Zhang, NY (reprint author), Penn State Univ, Dept Biomed Engn, Huck Inst Life Sci, W341 Millennium Sci Complex, University Pk, PA 16802 USA. EM nuz2@psu.edu RI Liang, Zhfieng/A-4914-2016; Liu, Xiao/C-5943-2016 OI Liang, Zhfieng/0000-0001-7940-3467; FU National Institutes of Health from the National Institute of Mental Health [R01MH098003]; National Institutes of Health from the National Institute of Neurological Disorders and Stroke [R01NS085200] FX We thank Ms. Christina Hamilton for editing the manuscript. The work was also supported by the National Institutes of Health, Grant Numbers R01MH098003 (PI: Nanyin Zhang, PhD) from the National Institute of Mental Health and R01NS085200 (PI: Nanyin Zhang, PhD) from the National Institute of Neurological Disorders and Stroke. NR 69 TC 11 Z9 11 U1 1 U2 19 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1053-8119 EI 1095-9572 J9 NEUROIMAGE JI Neuroimage PD JAN 1 PY 2015 VL 104 BP 89 EP 99 DI 10.1016/j.neuroimage.2014.10.013 PG 11 WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA AU1PZ UT WOS:000345393800009 PM 25315787 ER PT J AU Golestani, AM Chang, C Kwinta, JB Khatamian, YB Chen, JJ AF Golestani, Ali M. Chang, Catie Kwinta, Jonathan B. Khatamian, Yasha B. Chen, J. Jean TI Mapping the end-tidal CO2 response function in the resting-state BOLD fMRI signal: Spatial specificity, test-retest reliability and effect of fMRI sampling rate SO NEUROIMAGE LA English DT Article DE Resting-state fMRI; Physiological noise; Carbon dioxide; Respiratory volume; Heart rate variability; Cardiac variability; Multi-slice fMRI; Multiband fMRI ID CEREBRAL-BLOOD-FLOW; HEART-RATE; CARBON-DIOXIDE; CEREBROVASCULAR REACTIVITY; FLUCTUATIONS; RESPIRATION; BRAIN; VARIABILITY; ARTERIAL; HUMANS AB The blood oxygenation level dependent (BOLD) signal measures brain function indirectly through physiological processes and hence is susceptible to global physiological changes. Specifically, fluctuations in end-tidal CO2 (PETCO2), in addition to cardiac rate variation (CRV), and respiratory volume per time (RVT) variations, have been known to confound the resting-state fMRI (rs-fMRI) signal. Previous studies addressed the resting-state fMRI response function to CRV and RVT, but no attempt has been made to directly estimate the voxel-wise response function to PETCO2. Moreover, the potential interactions among PETCO2, CRV, and RVT necessitate their simultaneous inclusion in a multi-regression model to estimate the PETCO2 response. In this study, we use such a model to estimate the voxel-wise PETCO2 response functions directly from rs-fMRI data of nine healthy subjects. We also characterized the effect of sampling rate (TR=2 seconds vs. 323 ms) on the temporal and spatial variability of the PETCO2 response function in addition to that of CRV and RVT. In addition, we assess the test-retest reproducibility of the response functions to PETCO2, CRV and RVT. We found that despite overlaps across their spatial patterns, PETCO2 explains a unique portion of the rs-fMRI signal variance compared to RVT and CRV. We also found the shapes of the estimated responses are very similar between long-and short-TR data, although responses estimated from short-TR data have higher reproducibility. Crown Copyright (C) 2014 Published by Elsevier Inc. All rights reserved. C1 [Golestani, Ali M.; Kwinta, Jonathan B.; Khatamian, Yasha B.; Chen, J. Jean] Rotman Res Inst, Baycrest Ctr, Toronto, ON M6A 2E1, Canada. [Chang, Catie] NINDS, Adv MRI Sect, Lab Funct & Mol Imaging, NIH, Bethesda, MD 20892 USA. [Kwinta, Jonathan B.; Chen, J. Jean] Univ Toronto, Dept Med Biophys, Toronto, ON M5S 1A1, Canada. RP Golestani, AM (reprint author), Rotman Res Inst, 3560 Bathurst St, Toronto, ON M6A 2E1, Canada. EM agolestani@research.baycrest.org FU Natural Sciences and Engineering Council of Canada (NSERC); Canadian Institutes of Health Research (CIHR) FX This research was supported by grant funding from the Natural Sciences and Engineering Council of Canada (NSERC) and the Canadian Institutes of Health Research (CIHR). NR 55 TC 7 Z9 7 U1 1 U2 8 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1053-8119 EI 1095-9572 J9 NEUROIMAGE JI Neuroimage PD JAN 1 PY 2015 VL 104 BP 266 EP 277 DI 10.1016/j.neuroimage.2014.10.031 PG 12 WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA AU1PZ UT WOS:000345393800026 PM 25462695 ER PT J AU Voss, SD Glade-Bender, J Spunt, SL DuBois, SG Widemann, BC Park, JR Leary, SES Nelson, MD Adamson, PC Blaney, SM Weigel, B AF Voss, Stephan D. Glade-Bender, Julia Spunt, Sheri L. DuBois, Steven G. Widemann, Brigitte C. Park, Julie R. Leary, Sarah E. S. Nelson, Marvin D. Adamson, Peter C. Blaney, Susan M. Weigel, Brenda TI Growth Plate Abnormalities in Pediatric Cancer Patients Undergoing Phase 1 Anti-Angiogenic Therapy: A Report From the Children's Oncology Group Phase I Consortium SO PEDIATRIC BLOOD & CANCER LA English DT Article DE anti-angiogenic therapy; developing growth plate; physeal toxicity ID REFRACTORY SOLID TUMORS; SKELETAL RADIOGRAPHIC CHANGES; SAFETY EVALUATION; TRIAL; VEGF; BEVACIZUMAB; NEUROBLASTOMA; RECEPTORS; SUNITINIB; ADOLESCENTS AB BackgroundPre-clinical studies suggest that anti-angiogenic agents may be toxic to the developing growth plate. The purpose of this study was to evaluate the incidence of growth plate abnormalities in children with refractory cancer undergoing anti-angiogenic therapy. ProcedureTargeted radiographic studies from 53 subjects enrolled on six separate Children's Oncology Group Phase 1 and Pilot Consortium clinical trials evaluating new anti-cancer agents interfering with angiogenesis were reviewed. Subjects received tyrosine kinase inhibitors with anti-angiogenic effects (n=35), monoclonal antibodies targeting vascular endothelial growth factor (VEGF) (n=13), or angiopoietin (n=5). Radiographs of their distal femur/proximal tibia were obtained at baseline. Follow-up radiographs were obtained after odd-numbered treatment cycles in patients with open growth plates who did not experience disease progression prior to cycle 3. ResultsBaseline and follow-up growth plate radiographs were acquired in 48/53 (90%) of patients. Five patients (9.4%), all of whom received a specific VEGF/VEGFR blocking agent (sunitinib [n=1] or pazopanib [n=4]), had growth plate abnormalities. Four patients had growth plate widening that was apparent on at least two successive radiographs, but was not confirmed by MRI. The fifth patient had progressive growth plate widening and evidence of physeal cartilage hypertrophy on MRI. Subsequent off treatment radiographs showed that the growth plate changes were reversible. ConclusionGrowth plate abnormalities occur in a small, but relevant number of patients undergoing anti-angiogenic therapy. These results support the need for growth plate monitoring in children with open growth plates who are receiving anti-angiogenic therapy, and for improved methods to assess toxicity of anti-angiogenic agents to the developing skeleton. Pediatr Blood Cancer 2015;62:45-51. (c) 2014 Wiley Periodicals, Inc. C1 [Voss, Stephan D.] Boston Childrens Hosp, Dept Radiol, Dana Farber Canc Inst, Boston, MA 02115 USA. [Glade-Bender, Julia] Columbia Univ, Med Ctr, Dept Pediat Oncol, New York, NY USA. [Spunt, Sheri L.] Stanford Univ, Dept Pediat Hematol Oncol, Lucile Packard Childrens Hosp, Palo Alto, CA 94304 USA. [DuBois, Steven G.] UCSF Med Ctr Parnassus, Dept Pediat Hematol Oncol, San Francisco, CA USA. [Widemann, Brigitte C.] NCI, Dept Pharmacol & Expt Therapeut, Pediat Oncol Branch, CCR,Mark O Hatfield Warren Grant Magnuson Clin Ct, Bethesda, MD 20892 USA. [Park, Julie R.; Leary, Sarah E. S.] Seattle Childrens Hosp, Dept Hematol Oncol, Seattle, WA USA. [Nelson, Marvin D.] Childrens Hosp Los Angeles, Dept Radiol, Los Angeles, CA 90027 USA. [Adamson, Peter C.] Childrens Hosp Philadelphia, Abramson Res Ctr, Philadelphia, PA 19104 USA. [Blaney, Susan M.] Baylor Coll Med, Texas Childrens Canc Ctr, Houston, TX 77030 USA. [Weigel, Brenda] Univ Minnesota, Amplatz Childrens Hosp, Div Hematol & Oncol, Minneapolis, MN USA. RP Voss, SD (reprint author), Boston Childrens Hosp, Dept Radiol, Dana Farber Canc Inst, 300 Longwood Ave, Boston, MA 02115 USA. EM stephan.voss@childrens.harvard.edu OI Leary, Sarah/0000-0003-0225-6184 FU NCI NIH HHS [UM1 CA097452, 5UM1 CA097452-12] NR 39 TC 4 Z9 4 U1 0 U2 6 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1545-5009 EI 1545-5017 J9 PEDIATR BLOOD CANCER JI Pediatr. Blood Cancer PD JAN PY 2015 VL 62 IS 1 BP 45 EP 51 DI 10.1002/pbc.25229 PG 7 WC Oncology; Hematology; Pediatrics SC Oncology; Hematology; Pediatrics GA AU0NG UT WOS:000345319300010 PM 25257751 ER PT J AU Carol, H Fan, MMY Harasym, TO Boehm, I Mayer, LD Houghton, P Smith, MA Lock, RB AF Carol, Hernan Fan, Mannie M. Y. Harasym, Troy O. Boehm, Ingrid Mayer, Lawrence D. Houghton, Peter Smith, Malcolm A. Lock, Richard B. TI Efficacy of CPX-351, (Cytarabine: Daunorubicin) Liposome Injection, Against Acute Lymphoblastic Leukemia (ALL) Xenograft Models of the Pediatric Preclinical Testing Program SO PEDIATRIC BLOOD & CANCER LA English DT Article DE acute leukemia; CPX-351; efficacy; pharmacokinetics; synergy ID ACUTE MYELOID-LEUKEMIA; ACUTE LYMPHOCYTIC-LEUKEMIA; ADULT PATIENTS; 1ST RELAPSE; ARA-C; THERAPY; CYTARABINEDAUNORUBICIN; COMBINATION; FORMULATION; IDARUBICIN AB BackgroundCPX-351, a liposomal formulation of cytarabine and daunorubicin co-encapsulated at an optimized synergistic 5:1 molar ratio, has demonstrated improved clinical outcomes over conventional cytarabine/daunorubicin treatment in a randomized phase 2 trial in patients with AML as well as superior efficacy against preclinical leukemia models when compared to the free drugs in combination. ProceduresGiven the promising phase 2 data, limited toxicities observed, and the known clinical activities of cytarabine/daunorubicin, we assessed the efficacy of CPX-351 against a panel of childhood ALL xenograft models. Plasma pharmacokinetics of cytarabine and daunorubicin following CPX-351 treatment were determined by HPLC in order to correlate efficacy with drug exposure. ResultsCPX-351, at a dose of 5units/kg (corresponding to 5mg/kg cytarabine and 2.2mg/kg daunorubicin), was highly efficacious against all xenografts tested, inducing complete responses in four B-lineage xenografts and partial response in one T-lineage xenograft. These therapeutic responses were achieved with CPX-351 doses that provided drug exposures (based on C-max and AUC) comparable to those observed in patients with AML. ConclusionsThese results suggest that CPX-351 may be a promising chemotherapeutic to be utilized in the treatment of ALL and support its testing in pediatric patients with leukemia. Pediatr Blood Cancer 2015;62:65-71. (c) 2014 Wiley Periodicals, Inc. C1 [Carol, Hernan; Boehm, Ingrid; Lock, Richard B.] Univ New S Wales, Childrens Canc Inst Australia Med Res, Sydney, NSW, Australia. [Fan, Mannie M. Y.; Harasym, Troy O.; Mayer, Lawrence D.] Celator Pharmaceut Corp, Vancouver, BC, Canada. [Houghton, Peter] Nationwide Childrens Hosp, Columbus, OH USA. [Smith, Malcolm A.] NCI, Canc Therapy Evaluat Program, Bethesda, MD 20892 USA. RP Lock, RB (reprint author), Childrens Canc Inst Australia, Leukaemia Biol Program, Lowy Canc Res Ctr, High St, Randwick, NSW 2031, Australia. EM rlock@ccia.unsw.edu.au RI Lock, Richard/G-4253-2013 FU NCI NIH HHS [CA108786, CA21765, N01-CM-42216, N01CM42216, P30 CA021765, P50 CA108786] NR 38 TC 7 Z9 7 U1 1 U2 16 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1545-5009 EI 1545-5017 J9 PEDIATR BLOOD CANCER JI Pediatr. Blood Cancer PD JAN PY 2015 VL 62 IS 1 BP 65 EP 71 DI 10.1002/pbc.25133 PG 7 WC Oncology; Hematology; Pediatrics SC Oncology; Hematology; Pediatrics GA AU0NG UT WOS:000345319300013 PM 25203866 ER PT J AU Smith, MA Hampton, OA Reynolds, CP Kang, MH Maris, JM Gorlick, R Kolb, EA Lock, R Carol, H Keir, ST Wu, JR Kurmasheva, RT Wheeler, DA Houghton, PJ AF Smith, Malcolm A. Hampton, Oliver A. Reynolds, C. Patrick Kang, Min H. Maris, John M. Gorlick, Richard Kolb, E. Anders Lock, Richard Carol, Hernan Keir, Stephen T. Wu, Jianrong Kurmasheva, Raushan T. Wheeler, David A. Houghton, Peter J. TI Initial Testing (Stage 1) of the PARP Inhibitor BMN 673 by the Pediatric Preclinical Testing Program: PALB2 Mutation Predicts Exceptional In Vivo Response to BMN 673 SO PEDIATRIC BLOOD & CANCER LA English DT Article DE developmental therapeutics; PALB2; PARP inhibitor; preclinical testing ID BREAST-CANCER SUSCEPTIBILITY; FANCONI-ANEMIA; HOMOLOGOUS RECOMBINATION; POLY(ADP-RIBOSE) POLYMERASE; BIALLELIC MUTATIONS; MAMMARY-TUMORS; BRCA2; MEDULLOBLASTOMA; REPAIR; CELLS AB BackgroundBMN 673 is a potent inhibitor of poly-ADP ribose polymerase (PARP) that is in clinical testing with a primary focus on BRCA-mutated cancers. BMN 673 is active both through inhibiting PARP catalytic activity and by tightly trapping PARP to DNA at sites of single strand breaks. ProcedureBMN 673 was tested in vitro at concentrations ranging from 0.1nM to 1M and in vivo at a daily dose of 0.33mg/kg administered orally twice daily (Mon-Fri) and once daily on weekends (solid tumors) for 28 days. ResultsThe median relative IC50 (rIC(50)) concentration against the PPTP cell lines was 25.8nM. The median rIC(50) for the Ewing cell lines was lower than for the remaining cell lines (6.4 vs. 31.1nM, respectively). In vivo BMN 673 induced statistically significant differences in EFS distribution in 17/43 (39.5%) xenograft models. Three objective regressions were observed: a complete response (CR) in a medulloblastoma line (BT-45), a maintained CR in a Wilms tumor line (KT-10), and a maintained CR in an ependymoma line (BT-41). BMN 673 maintained its high level of activity against KT-10 with a threefold reduction in dose. KT-10 possesses a truncating mutation in PALB2 analogous to PALB2 mutations associated with hereditary breast and ovarian cancer that abrogate homologous recombination (HR) repair. ConclusionsThe PPTP results suggest that single agent BMN 673 may have limited clinical activity against pediatric cancers. Single agent activity is more likely for patients whose tumors have defects in HR repair. Pediatr Blood Cancer 2015;62:91-98. (c) 2014 Wiley Periodicals, Inc. C1 [Smith, Malcolm A.] NCI, Canc Therapy Evaluat Program, Bethesda, MD 20892 USA. [Hampton, Oliver A.; Wheeler, David A.] Baylor Coll Med, Human Genome Sequencing Ctr, Houston, TX 77030 USA. [Hampton, Oliver A.; Wheeler, David A.] Baylor Coll Med, Dept Mol & Human Genet, Houston, TX 77030 USA. [Reynolds, C. Patrick; Kang, Min H.] Texas Tech Univ, Hlth Sci Ctr, Lubbock, TX 79430 USA. [Maris, John M.] Univ Penn, Childrens Hosp Philadelphia, Sch Med, Philadelphia, PA 19104 USA. [Maris, John M.] Abramson Family Canc Res Inst, Philadelphia, PA USA. [Gorlick, Richard] Childrens Hosp Montefiore, Bronx, NY USA. [Kolb, E. Anders] Alfred I DuPont Hosp Children, Wilmington, DE USA. [Lock, Richard; Carol, Hernan] Childrens Canc Inst Australia Med Res, Randwick, NSW, Australia. [Keir, Stephen T.] Duke Univ, Med Ctr, Durham, NC USA. [Wu, Jianrong] St Jude Childrens Res Hosp, Memphis, TN 38105 USA. [Kurmasheva, Raushan T.; Houghton, Peter J.] Nationwide Childrens Hosp, Columbus, OH USA. RP Smith, MA (reprint author), NCI, 9609 Med Ctr Dr,RM 5-W414,MSC 9737, Bethesda, MD 20892 USA. EM malcolm.smith@nih.gov RI Lock, Richard/G-4253-2013; OI Reynolds, C. Patrick/0000-0002-2827-8536 FU Intramural NIH HHS [Z99 CA999999]; NCI NIH HHS [CA21765, N01 CM042216, N01-CM-42216, N01-CM91001-03, N01CM42216, P30 CA021765, P50 CA108786] NR 48 TC 12 Z9 13 U1 0 U2 10 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1545-5009 EI 1545-5017 J9 PEDIATR BLOOD CANCER JI Pediatr. Blood Cancer PD JAN PY 2015 VL 62 IS 1 BP 91 EP 98 DI 10.1002/pbc.25201 PG 8 WC Oncology; Hematology; Pediatrics SC Oncology; Hematology; Pediatrics GA AU0NG UT WOS:000345319300017 PM 25263539 ER PT J AU Lebel, A Yacobovich, J Krasnov, T Koren, A Levin, C Kaplinsky, C Ravel-Vilk, S Laor, R Attias, D Ben Barak, A Shtager, D Stein, J Kuperman, A Miskin, H Dgany, O Giri, N Alter, BP Tamary, H AF Lebel, Asaf Yacobovich, Joanne Krasnov, Tanya Koren, Ariel Levin, Carina Kaplinsky, Chaim Ravel-Vilk, Shoshana Laor, Ruth Attias, Dina Ben Barak, Ayelet Shtager, Dalia Stein, Jerry Kuperman, Amir Miskin, Hagit Dgany, Orly Giri, Neelam Alter, Blanche P. Tamary, Hannah TI Genetic Analysis and Clinical Picture of Severe Congenital Neutropenia in Israel SO PEDIATRIC BLOOD & CANCER LA English DT Article DE bone marrow failure; molecular genetics; neutropenia ID CYCLIC NEUTROPENIA; G6PC3 MUTATIONS; HAX1; ELA2; DEFICIENCY; ELASTASE; GFI1; HETEROGENEITY; DIAGNOSIS; SPECTRUM AB BackgroundThe relative frequency of mutated genes among patients with severe congenital neutropenia (SCN) may differ between various ethnic groups. To date, few population-based genetic studies have been reported. This study describes the genetic analysis of 32 Israeli patients with SCN. ProceduresClinical data were retrieved from the prospective Israeli Inherited Bone Marrow Failure Registry. Recruitment included living and deceased patients who were diagnosed between 1982 and 2012, for whom molecular diagnosis was performed. ELANE, HAX1 and G6PC3 genes were sequenced in all patients, and GFI-1 and WAS genes were sequenced if other genes were wildtype. ResultsEleven patients (34%) had heterozygous mutations in ELANE (10 kindreds), eight (25%) had homozygous mutations in G6PC3 (5 kindreds) and 13 (41%) had no detected mutations. No patients had mutations in HAX1 or WAS. Four of the eight patients with G6PC3 mutations had congenital anomalies. The probability of survival for all patients was 50% at age of 18. Deaths were mainly due to sepsis (5 patients, 4/5 not responding to G-CSF, none with G6PC3 mutation). Two patients developed acute myelogenous leukemia (AML) and one myelodysplastic syndrome (MDS), none with G6PC3 mutation. ConclusionsWe found a unique pattern of SCN mutations in Israel with homozygous G6PC3 mutations in eight (25%) patients, the highest frequency described so far. HAX1 mutations, reported mainly in Sweden and Iran, were absent. Patients with G6PC3 mutations had congenital anomalies, appeared to have a better response to G-CSF, and so far have not developed AML or MDS. Pediatr Blood Cancer 2015;62:103-108. (c) 2014 Wiley Periodicals, Inc. C1 [Lebel, Asaf] Schneider Childrens Med Ctr Israel, Dept Pediat B, IL-49202 Petah Tiqwa, Israel. [Lebel, Asaf; Yacobovich, Joanne; Stein, Jerry; Tamary, Hannah] Tel Aviv Univ, Sackler Fac Med, IL-69978 Tel Aviv, Israel. [Yacobovich, Joanne; Tamary, Hannah] Schneider Childrens Med Ctr Israel, Pediat Hematol Oncol Dept, IL-49202 Petah Tiqwa, Israel. [Krasnov, Tanya; Dgany, Orly; Tamary, Hannah] Felsenstein Med Res Ctr, Pediat Hematol Lab, Petah Tiqwa, Israel. [Koren, Ariel; Levin, Carina] HaEmek Med Ctr, Pediat Hematol Unit, Afula, Israel. [Kaplinsky, Chaim] Chaim Sheba Med Ctr, Pediat Hematol Oncol Dept, IL-52621 Tel Hashomer, Israel. [Ravel-Vilk, Shoshana] Hadassah Med Ctr, Pediat Hematol Oncol Dept, IL-91120 Jerusalem, Israel. [Laor, Ruth; Attias, Dina] Bnai Zion Med Ctr, Pediat Hematol Oncol Unit, Haifa, Israel. [Ben Barak, Ayelet] Rambam Med Ctr, Pediat Hematol Oncol Dept, Haifa, Israel. [Shtager, Dalia] Kaplan Med Ctr, Pediat Hematol Oncol Unit, Rehovot, Israel. [Stein, Jerry] Schneider Childrens Med Ctr Israel, Bone Marrow Transplant Unit, IL-49202 Petah Tiqwa, Israel. [Kuperman, Amir] Bar Ilan Univ, Pediat Hematol Clin, Galilee Med Ctr, Fac Med Galilee, Safed, Israel. [Kuperman, Amir] Bar Ilan Univ, Blood Coagulat Serv, Galilee Med Ctr, Fac Med Galilee, Safed, Israel. [Miskin, Hagit] Shaare Zedek Med Ctr, Pediat Hematol Unit, Jerusalem, Israel. [Giri, Neelam; Alter, Blanche P.] NCI, Clin Genet Branch, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. RP Tamary, H (reprint author), Schneider Childrens Med Ctr Israel, Hematol Unit, 14 Kaplan St, IL-49202 Petah Tiqwa, Israel. EM htamary@post.tau.ac.il FU Intramural NIH HHS NR 35 TC 1 Z9 1 U1 2 U2 6 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1545-5009 EI 1545-5017 J9 PEDIATR BLOOD CANCER JI Pediatr. Blood Cancer PD JAN PY 2015 VL 62 IS 1 BP 103 EP 108 DI 10.1002/pbc.25251 PG 6 WC Oncology; Hematology; Pediatrics SC Oncology; Hematology; Pediatrics GA AU0NG UT WOS:000345319300019 PM 25284454 ER PT J AU Mitchell, CD Chernoff, MC Seage, GR Purswani, MU Spiegel, HML Zilleruelo, G Abitbol, C Heckman, B Ponce, CB Oleske, JM AF Mitchell, Charles D. Chernoff, Miriam C. Seage, George R., III Purswani, Murli U. Spiegel, Hans M. L. Zilleruelo, Gaston Abitbol, Carolyn Heckman, Barbara Ponce, Christopher B. Oleske, James M. CA IMPAACT 219 219C Study Team TI Predictors of resolution and persistence of renal laboratory abnormalities in pediatric HIV infection SO PEDIATRIC NEPHROLOGY LA English DT Article DE HIV; HIV renal disease; HAART; Pediatric; Perinatal ID CHRONIC KIDNEY-DISEASE; ANTIRETROVIRAL THERAPY; CHILDREN; NEPHROPATHY; ASSOCIATION; ADOLESCENTS; CHILDHOOD; SPECTRUM; HISTORY; COHORT AB Among human immunodeficiency virus (HIV)-infected youth, the role of renal disease (RD) and its management has become increasingly important as these children/adolescents mature into young adults. The identification of predictors of abnormal renal laboratory events (RLE) may be helpful in the management of their HIV infection and its associated renal complications. Data collected from HIV-infected youth followed for a parts per thousand yenaEuro parts per thousand 48 months were analyzed to identify predictors of resolution versus persistence of RLE and determine the utility of RLE to predict the onset of RD. Analysis included descriptive and inferential methods using a multivariable extended Cox proportional hazards model. Of the 1,874 at-risk children enrolled in the study, 428 (23 %) developed RLE, which persisted in 229 of these (54 %). CD4 percentages of < 25 % [hazard ratio (HR) 0.63, p < 0.002) and an HIV viral load of > 100,000 copies/ml (HR 0.31, p < 0.01) were associated with reduced rates of resolution, while in most cases exposure to highly active antiretroviral therapy (HAART)/nephrotoxic HAART prior to or subsequent to RLE were not. Persistence of RLE was 88 % sensitive for identifying new RD. Negative predictive values for RD were > 95 % for both the at-risk cohort and those with RLE. Advanced HIV disease predicted persistence of RLE in HIV-infected youth. Persistent RLE were useful for identifying RD. C1 [Mitchell, Charles D.] Univ Miami, Miller Sch Med, Div Infect Dis & Immunol, Batchelor Childrens Res Inst,Dept Pediat, Miami, FL 33136 USA. [Chernoff, Miriam C.; Seage, George R., III] Harvard Univ, Sch Publ Hlth, Ctr Biostat AIDS Res, Boston, MA 02115 USA. [Seage, George R., III] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. [Purswani, Murli U.] Albert Einstein Coll Med, Bronx Lebanon Hosp Ctr, Div Pediat Infect Dis, Boston, MA USA. [Spiegel, Hans M. L.] NIAID, HJF DAIDS, NIH, US Dept HHS, Bethesda, MD 20892 USA. [Zilleruelo, Gaston; Abitbol, Carolyn] Univ Miami, Miller Sch Med, Dept Pediat, Div Pediat Nephrol, Miami, FL 33136 USA. [Heckman, Barbara] Frontier Sci & Technol Res Fdn Inc, Amherst, NY USA. [Ponce, Christopher B.; Oleske, James M.] Rutgers State Univ, New Jersey Med Sch, Dept Pediat, Piscataway, NJ 08855 USA. RP Mitchell, CD (reprint author), Univ Miami, Miller Sch Med, Div Infect Dis & Immunol, Batchelor Childrens Res Inst,Dept Pediat, Room 286,1580 NW 10th Ave, Miami, FL 33136 USA. EM cmitchel@med.miami.edu RI Oleske, James/C-1951-2016; OI Oleske, James/0000-0003-2305-5605; Bonagura, Vincent/0000-0002-0681-2099 FU National Institute of Allergy and Infectious Diseases (NIAID) [U01 AI068632]; Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD); National Institute of Mental Health (NIMH) [AI068632]; Statistical and Data Analysis Center at Harvard School of Public Health, under the National Institute of Allergy and Infectious Diseases [5 U01 AI41110]; Pediatric AIDS Clinical Trials Group (PACTG); IMPAACT Group [1 U01 AI068616]; National Institute of Allergy and Infectious Diseases (NIAID); NICHD International and Domestic Pediatric and Maternal HIV Clinical Trials Network - NICHD [N01-DK-9-001/HHSN267200800001C]; National Institutes of Allergy and Infectious Diseases, National Institutes of Health, Department of Health and Human Services [HHSN272200800014C] FX The authors would like to thank the researchers and institutions involved in the conduct of 219C as well as the leadership and participants of the P219/219C protocol team and the 219C iDACS617 Working Group. The authors are grateful for the contributions of Joyce Kraimer, Carol Elgie, Barbara Heckman, Shirley Traite, and Nathan Tryon. Overall support for the International Maternal Pediatric Adolescent AIDS Clinical Trials Group (IMPAACT) was provided by the National Institute of Allergy and Infectious Diseases (NIAID) [U01 AI068632], the Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD), and the National Institute of Mental Health (NIMH) [AI068632]. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. This work was supported by the Statistical and Data Analysis Center at Harvard School of Public Health, under the National Institute of Allergy and Infectious Diseases cooperative agreement #5 U01 AI41110 with the Pediatric AIDS Clinical Trials Group (PACTG) and #1 U01 AI068616 with the IMPAACT Group. Support of the sites was provided by the National Institute of Allergy and Infectious Diseases (NIAID) the NICHD International and Domestic Pediatric and Maternal HIV Clinical Trials Network funded by NICHD (contract number N01-DK-9-001/HHSN267200800001C). This project has been funded in whole or in part with Federal funds from the National Institutes of Allergy and Infectious Diseases, National Institutes of Health, Department of Health and Human Services, under Contract No. HHSN272200800014C. The authors also thank the individual staff members and sites who have participated in the conduct of this study, as provided in Appendix 1. NR 22 TC 1 Z9 1 U1 0 U2 3 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0931-041X EI 1432-198X J9 PEDIATR NEPHROL JI Pediatr. Nephrol. PD JAN PY 2015 VL 30 IS 1 BP 153 EP 165 DI 10.1007/s00467-014-2909-1 PG 13 WC Pediatrics; Urology & Nephrology SC Pediatrics; Urology & Nephrology GA AU1XP UT WOS:000345411200017 PM 25149850 ER PT J AU Nuche-Berenguer, B Moreno, P Jensen, RT AF Nuche-Berenguer, Bernardo Moreno, Paola Jensen, R. T. TI Elucidation of the Roles of the Src Kinases in Pancreatic Acinar Cell Signaling SO JOURNAL OF CELLULAR BIOCHEMISTRY LA English DT Article DE Src; PANCREATITIS; PANCREATIC ACINI; CCK; SIGNALING; FOCAL ADHESION KINASES; MAP KINASES ID FOCAL ADHESION KINASE; TYROSINE PHOSPHORYLATION; FAMILY KINASES; C-SRC; GASTROINTESTINAL HORMONES/NEUROTRANSMITTERS; ACTIN CYTOSKELETON; CATALYTIC-ACTIVITY; GROWTH-FACTORS; BINDING-SITE; IN-VIVO AB Recent studies report the Src-family kinases (SFK's) are important in a number of physiological and pathophysiological responses of pancreatic acinar cells (pancreatitis, growth, apoptosis); however, the role of SFKs in various signaling cascades important in mediating these cell functions is either not investigated or unclear. To address this we investigated the action of SFKs in these signaling cascades in rat pancreatic acini by modulating SFK activity using three methods: adenovirus-induced expression of an inactive dominant-negative CSK (Dn-CSK-Advirus) or wild-type CSK (Wt-CSK-Advirus), which activate or inhibit SFK, respectively, or using the chemical inhibitor, PP2, with its inactive control, PP3. CCK (0.3, 100nM) and TPA (1M) activated SFK and altered the activation of FAK proteins (PYK2, p125(FAK)), adaptor proteins (p130(CAS), paxillin), MAPK (p42/44, JNK, p38), Shc, PKC (PKD, MARCKS), Akt but not GSK3-. Changes in SFK activity by using the three methods of altering SFK activity affected CCK/TPAs activation of SFK, PYK2, p125(FAK), p130(CAS), Shc, paxillin, Akt but not p42/44, JNK, p38, PKC (PKD, MARCKS) or GSK3-. With chemical inhibition the active SFK inhibitor, PP2, but not the inactive control analogue, PP3, showed these effects. For all stimulated changes pre-incubation with both adenoviruses showed similar effects to chemical inhibition of SFK activity. In conclusion, using three different approaches to altering Src activity allowed us to define fully for the first time the roles of SFKs in acinar cell signaling. Our results show that in pancreatic acinar cells, SFKs play a much wider role than previously reported in activating a number of important cellular signaling cascades shown to be important in mediating both acinar cell physiological and pathophysiological responses. J. Cell. Biochem. 116: 22-36, 2015. Published 2014. This article is a U.S. Government work and is in the public domain in the USA. C1 [Nuche-Berenguer, Bernardo; Moreno, Paola; Jensen, R. T.] Natl Inst Diabet & Digest & Kidney Dis, Digest Dis Branch, NIH, Bethesda, MD 20892 USA. RP Jensen, RT (reprint author), NIDDK, NIH, DDB, Bldg 10,Rm 9C-103,10 Ctr Dr MSC 1804, Bethesda, MD 20892 USA. EM robertj@bdg10.niddk.nih.gov FU NIDDK, NIH FX Grant sponsor: NIDDK, NIH. NR 50 TC 4 Z9 4 U1 0 U2 8 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0730-2312 EI 1097-4644 J9 J CELL BIOCHEM JI J. Cell. Biochem. PD JAN PY 2015 VL 116 IS 1 BP 22 EP 36 DI 10.1002/jcb.24895 PG 15 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA AT2YB UT WOS:000344799200004 PM 25079913 ER PT S AU Katebi, AR Sankar, K Jia, K Jernigan, RL AF Katebi, Ataur R. Sankar, Kannan Jia, Kejue Jernigan, Robert L. BE Kukol, A TI The Use of Experimental Structures to Model Protein Dynamics SO MOLECULAR MODELING OF PROTEINS: 2ND EDITION SE Methods in Molecular Biology LA English DT Article; Book Chapter DE HIV-1 protease; Principal component analysis; Elastic network model; Protein dynamics; Acquired immunodeficiency syndrome; Protein data bank ID PRINCIPAL COMPONENT ANALYSIS; ELASTIC NETWORK MODELS; MOLECULAR-DYNAMICS; ATOMIC FLUCTUATIONS; ALIGNMENT ALGORITHM; GLOBULAR-PROTEINS; ANISOTROPY; ENSEMBLES; MOTIONS; ANHARMONICITY AB The number of solved protein structures submitted in the Protein Data Bank (PDB) has increased dramatically in recent years. For some specific proteins, this number is very high-for example, there are over 550 solved structures for HIV-1 protease, one protein that is essential for the life cycle of human immunodeficiency virus (HIV) which causes acquired immunodeficiency syndrome (AIDS) in humans. The large number of structures for the same protein and its variants include a sample of different conformational states of the protein. A rich set of structures solved experimentally for the same protein has information buried within the dataset that can explain the functional dynamics and structural mechanism of the protein. To extract the dynamics information and functional mechanism from the experimental structures, this chapter focuses on two methods-Principal Component Analysis (PCA) and Elastic Network Models (ENM). PCA is a widely used statistical dimensionality reduction technique to classify and visualize high-dimensional data. On the other hand, ENMs are well-established simple biophysical method for modeling the functionally important global motions of proteins. This chapter covers the basics of these two. Moreover, an improved ENM version that utilizes the variations found within a given set of structures for a protein is described. As a practical example, we have extracted the functional dynamics and mechanism of HIV-1 protease dimeric structure by using a set of 329 PDB structures of this protein. We have described, step by step, how to select a set of protein structures, how to extract the needed information from the PDB files for PCA, how to extract the dynamics information using PCA, how to calculate ENM modes, how to measure the congruency between the dynamics computed from the principal components (PCs) and the ENM modes, and how to compute entropies using the PCs. We provide the computer programs or references to software tools to accomplish each step and show how to use these programs and tools. We also include computer programs to generate movies based on PCs and ENM modes and describe how to visualize them. C1 [Katebi, Ataur R.; Sankar, Kannan; Jia, Kejue; Jernigan, Robert L.] NCI, NIH, Bethesda, MD 20892 USA. [Katebi, Ataur R.; Sankar, Kannan; Jia, Kejue; Jernigan, Robert L.] Iowa State Univ, LH Baker Ctr Bioinformat & Biol Stat, Interdept Program Bioinformat & Computat Biol, Ames, IA USA. RP Katebi, AR (reprint author), NCI, NIH, Bethesda, MD 20892 USA. FU NIGMS NIH HHS [R01GM072014, R01 GM073095, R01 GM072014] NR 37 TC 2 Z9 2 U1 0 U2 9 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DR, STE 208, TOTOWA, NJ 07512-1165 USA SN 1064-3745 BN 978-1-4939-1465-4; 978-1-4939-1464-7 J9 METHODS MOL BIOL JI Methods Mol. Biol. PY 2015 VL 1215 BP 213 EP 236 DI 10.1007/978-1-4939-1465-4_10 D2 10.1007/978-1-4939-1465-4 PG 24 WC Biochemical Research Methods; Biochemistry & Molecular Biology; Mathematical & Computational Biology SC Biochemistry & Molecular Biology; Mathematical & Computational Biology GA BB6DG UT WOS:000344689900011 PM 25330965 ER PT J AU Ballard, ED Patel, AB Ward, M Lamis, DA AF Ballard, Elizabeth D. Patel, Amee B. Ward, Martha Lamis, Dorian A. TI Future disposition and suicidal ideation: Mediation by depressive symptom clusters SO JOURNAL OF AFFECTIVE DISORDERS LA English DT Article DE Depression; Hopelessness; Suicidal ideation ID SOCIAL-DESIRABILITY-SCALE; COLLEGE-STUDENTS; HOPELESSNESS DEPRESSION; COGNITIVE VULNERABILITY; ATTRIBUTIONAL STYLE; BEHAVIOR; THINKING; PARASUICIDE; COMPONENTS; UNIVERSITY AB Background: In line with hopelessness theory, both increased negative expectancies and reduced positive expectancies for the future have been associated with suicidal ideation. This study evaluated two depression symptom clusters as mediators of the relationship between future disposition and suicide: subjective feelings of depression and self-blame. Methods: Data from 140 undergraduate students with moderate to severe depression symptoms are presented who completed the Beck Scale for Suicidal Ideation, Beck Depression Inventory, and the Future Disposition Inventory. Results: On mediation analysis, subjective depression mediated the relationship between positive disposition and suicidal ideation. In contrast, the relationship between negative disposition and suicidal ideation was mediated by self-blame. The reverse of these relationships was not significant. Limitations: This is a cross-sectional study of an undergraduate sample and results warrant replication in clinical samples with clinician-administered assessments. Conclusions: Findings suggest two potential pathways to suicidal thoughts with implications for assessment and treatment Depressed individuals with few positive expectations of the future may benefit from interventions focusing on subjective depression symptoms, such as sadness or anhedonia. For depressed individuals with negative expectations for the future, a clinical focus on negative attributions or sell blame may be warranted. Published by Elsevier B.V. C1 [Ballard, Elizabeth D.] NIMH, Expt Therapeut & Pathophysiol Branch, NIH, Bethesda, MD 20892 USA. [Patel, Amee B.] South Cent Mental Illness Res Educ & Clin Ctr MIR, GV Sonny Montgomery VA Med Ctr, Bethesda, MD USA. [Ward, Martha; Lamis, Dorian A.] Emory Univ, Sch Med, Atlanta, GA 30322 USA. RP Ballard, ED (reprint author), Bldg10,CRC 7-5541, Bethesda, MD 20892 USA. FU Intramural NIH HHS [Z99 MH999999] NR 49 TC 3 Z9 3 U1 1 U2 14 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0165-0327 EI 1573-2517 J9 J AFFECT DISORDERS JI J. Affect. Disord. PD JAN 1 PY 2015 VL 170 BP 1 EP 6 DI 10.1016/j.jad.2014.08.029 PG 6 WC Clinical Neurology; Psychiatry SC Neurosciences & Neurology; Psychiatry GA AS4ET UT WOS:000344226700001 PM 25217757 ER PT J AU Wang, SJ Li, D Petrick, N Sahiner, B Linguraru, MG Summers, RM AF Wang, Shijun Li, Diana Petrick, Nicholas Sahiner, Berkman Linguraru, Marius George Summers, Ronald M. TI Optimizing area under the ROC curve using semi-supervised learning SO PATTERN RECOGNITION LA English DT Article DE Receiver operating characteristic; AUC; Semi-supervised learning; Transfer learning; Semidefinite programming; RankBoost; SVMROC; SSLROC ID SUPPORT VECTOR MACHINES; CT COLONOGRAPHY; CLASSIFICATION; ALGORITHMS; AUC; TESTS AB Receiver operating characteristic (ROC) analysis is a standard methodology to evaluate the performance of a binary classification system. The area under the ROC curve (AUC) is a performance metric that summarizes how well a classifier separates two classes. Traditional AUC optimization techniques are supervised learning methods that utilize only labeled data (i.e., the true class is known for all data) to train the classifiers. In this work, inspired by semi-supervised and transductive learning, we propose two new AUC optimization algorithms hereby referred to as semi-supervised learning receiver operating characteristic (SSLROC) algorithms, which utilize unlabeled test samples in classifier training to maximize AUC. Unlabeled samples are incorporated into the AUC optimization process, and their ranking relationships to labeled positive and negative training samples are considered as optimization constraints. The introduced test samples will cause the learned decision boundary in a multidimensional feature space to adapt not only to the distribution of labeled training data, but also to the distribution of unlabeled test data. We formulate the semi-supervised AUC optimization problem as a semi-definite programming problem based on the margin maximization theory. The proposed methods SSLROC1 (1-norm) and SSLROC2 (2-norm) were evaluated using 34 (determined by power analysis) randomly selected datasets from the University of California, Irvine machine learning repository. Wilcoxon signed rank tests showed that the proposed methods achieved significant improvement compared with state-of-the-art methods. The proposed methods were also applied to a CT colonography dataset for colonic polyp classification and showed promising results.(1) Published by Elsevier Ltd. C1 [Wang, Shijun; Li, Diana; Summers, Ronald M.] NIH, Imaging Biomarkers & Comp Aided Diag Lab, Ctr Clin, Bethesda, MD 20892 USA. [Petrick, Nicholas; Sahiner, Berkman] US FDA, Ctr Devices & Radiol Hlth, Silver Spring, MD 20993 USA. [Linguraru, Marius George] Childrens Natl Hlth Syst, Sheikh Zayed Inst Pediat Surg Innovat, Washington, DC 20010 USA. [Linguraru, Marius George] George Washington Univ, Sch Med & Hlth Sci, Washington, DC 20037 USA. RP Summers, RM (reprint author), NIH, Imaging Biomarkers & Comp Aided Diag Lab, Ctr Clin, Bldg 10 Room 1C224D MSC 1182, Bethesda, MD 20892 USA. EM rms@nih.gov FU Intramural NIH HHS [ZIA CL040003-11] NR 54 TC 4 Z9 4 U1 1 U2 17 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0031-3203 EI 1873-5142 J9 PATTERN RECOGN JI Pattern Recognit. PD JAN PY 2015 VL 48 IS 1 BP 276 EP 287 DI 10.1016/j.patcog.2014.07.025 PG 12 WC Computer Science, Artificial Intelligence; Engineering, Electrical & Electronic SC Computer Science; Engineering GA AS3UR UT WOS:000344204000021 PM 25395692 ER PT S AU Kouprina, N Lee, NCO Kononenko, AV Samoshkin, A Larionov, V AF Kouprina, Natalay Lee, Nicholas C. O. Kononenko, Artem V. Samoshkin, Alexander Larionov, Vladimir BE Narayanan, K TI From Selective Full-Length Genes Isolation by TAR Cloning in Yeast to Their Expression from HAC Vectors in Human Cells SO BACTERIAL ARTIFICIAL CHROMOSOMES, 2ND EDITION SE Methods in Molecular Biology LA English DT Article; Book Chapter DE YAC; BAC; TAR cloning; Gene isolation; Human artificial chromosome (HAC) ID TRANSFORMATION-ASSOCIATED RECOMBINATION; HUMAN ARTIFICIAL CHROMOSOMES; SACCHAROMYCES-CEREVISIAE; COMPLEX GENOMES; FUNCTIONAL GENOMICS; PROSTATE-CANCER; SEQUENCE; REGION; EVOLUTION; LOCUS AB Transformation-associated recombination (TAR) cloning allows selective isolation of full-length genes and genomic loci as large circular Yeast Artificial Chromosomes (YACs) in yeast. The method has a broad application for structural and functional genomics, long-range haplotyping, characterization of chromosomal rearrangements, and evolutionary studies. In this paper, we describe a basic protocol for gene isolation by TAR as well as a method to convert TAR isolates into Bacterial Artificial Chromosomes (BACs) using a retrofitting vector. The retrofitting vector contains a 3 ' HPRT-loxP cassette to allow subsequent gene loading into a unique loxP site of the HAC-based (Human Artificial Chromosome) gene delivery vector. The benefit of combining the TAR gene cloning technology with the HAC gene delivery system for gene expression studies is discussed. C1 [Kouprina, Natalay; Lee, Nicholas C. O.; Kononenko, Artem V.; Samoshkin, Alexander; Larionov, Vladimir] NCI, Mol Pharmacol Lab, NIH, Bethesda, MD 20892 USA. RP Kouprina, N (reprint author), NCI, Mol Pharmacol Lab, NIH, Bethesda, MD 20892 USA. RI Lee, Nicholas/F-3668-2015; OI lee, nicholas/0000-0003-2628-6599 FU Intramural NIH HHS NR 39 TC 0 Z9 0 U1 1 U2 9 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DR, STE 208, TOTOWA, NJ 07512-1165 USA SN 1064-3745 BN 978-1-4939-1652-8; 978-1-4939-1651-1 J9 METHODS MOL BIOL JI Methods Mol. Biol. PY 2015 VL 1227 BP 3 EP 26 DI 10.1007/978-1-4939-1652-8_1 D2 10.1007/978-1-4939-1652-8 PG 24 WC Biochemical Research Methods; Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA BB4NQ UT WOS:000343243500002 PM 25239739 ER PT S AU David, A Yewdell, JW AF David, Alexandre Yewdell, Jonathan W. BE Hancock, R TI Applying the Ribopuromycylation Method to Detect Nuclear Translation SO NUCLEUS, 2ND EDITION SE Methods in Molecular Biology LA English DT Article; Book Chapter DE Nuclear translation; Puromycin; Ribopuromycylation; Ribosome; Emetine; Nascent chain ID PROTEIN-SYNTHESIS; INHIBITORS AB Protein translation in the nucleus has been controversial for more than four decades. To take a new look at this potentially important phenomenon, we adapted the RiboPuromycylation Method (RPM) which labels actively translating ribosomes in cells via standard immunofluorescence microscopy. RPM is based on puromycylation of nascent chains trapped on ribosomes by antibiotics which inhibit chain elongation, followed by cell permeabilization/fixation and detection of puromycylated nascent chains using a puromycin-specific monoclonal antibody. To adapt the method to the nucleus, we use NP-40 rather than digitonin to permeabilize cells because NP-40 enables better antibody penetration into the nucleoplasm and particularly the nucleoli, a region of high translation as shown by RPM. C1 [David, Alexandre] CNRS, UMR 5203, Montpellier, France. [David, Alexandre] INSERM, Montpellier, France. [David, Alexandre] UM1, Montpellier, France. [David, Alexandre] Inst Genom Fonct, UM2, Montpellier, France. [Yewdell, Jonathan W.] NIAID, Viral Dis Lab, Bethesda, MD 20892 USA. RP David, A (reprint author), CNRS, UMR 5203, Montpellier, France. FU Intramural NIH HHS NR 17 TC 3 Z9 3 U1 0 U2 8 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DR, STE 208, TOTOWA, NJ 07512-1165 USA SN 1064-3745 BN 978-1-4939-1680-1; 978-1-4939-1679-5 J9 METHODS MOL BIOL JI Methods Mol. Biol. PY 2015 VL 1228 BP 133 EP 142 DI 10.1007/978-1-4939-1680-1_11 D2 10.1007/978-1-4939-1680-1 PG 10 WC Biochemical Research Methods; Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA BB4SO UT WOS:000343313300012 PM 25311127 ER PT S AU Nakano, M Yamasaki, E Moss, J Hirayama, T Kurazono, H AF Nakano, Masayuki Yamasaki, Eiki Moss, Joel Hirayama, Toshiya Kurazono, Hisao BE Schatten, H Eisenstark, A TI Study of the Stn Protein in Salmonella; A Regulator of Membrane Composition and Integrity SO SALMONELLA: METHODS AND PROTOCOLS, 2ND EDITION SE Methods in Molecular Biology LA English DT Article; Book Chapter DE Salmonella; Stn protein; Bacterial membrane; Electron microscopy; Immunogold stain ID TYPHIMURIUM; ENTEROTOXIN; VIRULENCE; MICROSCOPY AB Our studies were undertaken to develop new insights into the function of the Salmonella Stn protein. An analysis of total cell membrane protein fraction suggested the possibility that Stn associates with OmpA. This possibility was confirmed by immunogold labeling using anti-OmpA antibody and far-western blotting. From these results, we conclude that Stn regulates membrane composition and integrity in Salmonella C1 [Nakano, Masayuki; Hirayama, Toshiya] Nagasaki Univ, Inst Trop Med, Dept Bacteriol, Sakamoto, Nagasaki, Japan. [Yamasaki, Eiki; Kurazono, Hisao] Obihiro Univ Agr & Vet Med, Dept Anim & Food Hyg, Obihiro, Hokkaido 080, Japan. [Moss, Joel] NHLBI, Cardiovasc & Pulm Branch, NIH, Bethesda, MD 20892 USA. RP Nakano, M (reprint author), Nagasaki Univ, Inst Trop Med, Dept Bacteriol, Sakamoto, Nagasaki, Japan. NR 9 TC 1 Z9 1 U1 0 U2 3 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DR, STE 208, TOTOWA, NJ 07512-1165 USA SN 1064-3745 BN 978-1-4939-1625-2; 978-1-4939-1624-5 J9 METHODS MOL BIOL JI Methods Mol. Biol. PY 2015 VL 1225 BP 127 EP 138 DI 10.1007/978-1-4939-1625-2_9 D2 10.1007/978-1-4939-1625-2 PG 12 WC Biochemical Research Methods; Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA BB4NJ UT WOS:000343241500010 PM 25253253 ER PT J AU Huang, P Wang, SJ Wang, XS Shen, GX Lin, J Wang, Z Guo, SW Cui, DX Yang, M Chen, XY AF Huang, Peng Wang, Shouju Wang, Xiansong Shen, Guangxia Lin, Jing Wang, Zhe Guo, Shouwu Cui, Daxiang Yang, Min Chen, Xiaoyuan TI Surface Functionalization of Chemically Reduced Graphene Oxide for Targeted Photodynamic Therapy SO JOURNAL OF BIOMEDICAL NANOTECHNOLOGY LA English DT Article DE Graphene Oxide; Polyvinylpyrrolidone; Chlorin e6; RGD; Photodynamic Therapy ID PHOTOTHERMAL THERAPY; BIOMEDICAL APPLICATIONS; GOLD NANOPARTICLES; CELLULAR UPTAKE; POLYVINYLPYRROLIDONE; THERANOSTICS; DELIVERY; PEPTIDE; CELLS; DOTS AB In this study, using chemically reduced graphene oxide (GO) as a model nanocarbon, we successfully developed a facile surface-functionalization strategy of nanocarbons to allow both biocompatibility and receptor targeted drug delivery. Polyvinylpyrrolidone (PVP) coating improves aqueous dispersibility and biocompatibility of GO, and provides anchoring sites for ACDCRGDCFCG peptide (RGD4C). Aromatic photosensitizer chlorin e6 (Ce6) can be effectively loaded into the rGO-PVP-RGD system via hydrophobic interactions and pi-pi stacking. The nanodelivery system can significantly increase the accumulation of Ce6 in tumor cells and lead to an improved photodynamic therapy (PDT) efficacy as compared to Ce6 alone. The facile surface functionalization strategy can be applied to other nanomaterials such as carbon nanotubes, and inorganic nanomaterials. C1 [Huang, Peng; Yang, Min] Jiangsu Inst Nucl Med, Key Lab Nucl Med, Jiangsu Key Lab Mol Nucl Med, Minist Hlth, Wuxi 214063, Jiangsu, Peoples R China. [Huang, Peng; Wang, Shouju; Lin, Jing; Wang, Zhe; Chen, Xiaoyuan] Natl Inst Biomed Imaging & Bioengn, Lab Mol Imaging & Nanomed LOMIN, NIH, Bethesda, MD 20892 USA. [Wang, Xiansong; Shen, Guangxia; Guo, Shouwu; Cui, Daxiang] Shanghai Jiao Tong Univ, Res Inst Micro Nano Sci & Technol, Shanghai 200240, Peoples R China. [Wang, Zhe] Xiamen Univ, Sch Publ Hlth, Ctr Mol Imaging & Translat Med, State Key Lab Mol Vaccinol & Mol Diagnost, Xiamen 361005, Peoples R China. RP Yang, M (reprint author), Jiangsu Inst Nucl Med, Key Lab Nucl Med, Jiangsu Key Lab Mol Nucl Med, Minist Hlth, Wuxi 214063, Jiangsu, Peoples R China. EM yangmin@jsinm.org; shawn.chen@nih.gov RI Huang, Peng/H-9985-2013; Huang, Peng/R-2480-2016 OI Huang, Peng/0000-0003-3651-7813 FU MOST [2010CB933901, 2011CB933100, 2013CB733802]; NSFC [81171399, 81101077]; National Significant New Drugs Creation Program [2012ZX09505-001-001]; Jiangsu Province Science and Technology Foundation [BE2012622, BK2011166, BL2012031]; Health Ministry of Jiangsu Province Fund [RC2011095, H201028]; Public service platform for Science and technology infrastructure construction project of Jiangsu Province [BM2012066]; Intramural Research Program (IRP), National Institute of Biomedical Imaging and Bioengineering (NIBIB), National Institutes of Health (NIH) FX This work is supported, in part, by MOST (2010CB933901, 2011CB933100 and 2013CB733802), NSFC (81171399 and 81101077), National Significant New Drugs Creation Program (2012ZX09505-001-001), Jiangsu Province Science and Technology Foundation (BE2012622, BK2011166 and BL2012031), Health Ministry of Jiangsu Province Fund (RC2011095 and H201028), Public service platform for Science and technology infrastructure construction project of Jiangsu Province (BM2012066), and the Intramural Research Program (IRP), National Institute of Biomedical Imaging and Bioengineering (NIBIB), National Institutes of Health (NIH). NR 39 TC 14 Z9 14 U1 10 U2 177 PU AMER SCIENTIFIC PUBLISHERS PI VALENCIA PA 26650 THE OLD RD, STE 208, VALENCIA, CA 91381-0751 USA SN 1550-7033 EI 1550-7041 J9 J BIOMED NANOTECHNOL JI J. Biomed. Nanotechnol. PD JAN PY 2015 VL 11 IS 1 BP 117 EP 125 DI 10.1166/jbn.2015.2055 PG 9 WC Nanoscience & Nanotechnology; Materials Science, Biomaterials SC Science & Technology - Other Topics; Materials Science GA AQ4TY UT WOS:000342793800008 PM 26301305 ER PT J AU Cruz-Topete, D Cidlowski, JA AF Cruz-Topete, Diana Cidlowski, John A. TI One Hormone, Two Actions: Anti- and Pro-Inflammatory Effects of Glucocorticoids SO NEUROIMMUNOMODULATION LA English DT Article DE Glucocorticoids; Stress hormones; Glucocorticoid receptor; Inflammation; Immunity; Pro-inflammatory and anti-inflammatory ID NF-KAPPA-B; INNATE IMMUNE-SYSTEM; P38 MAP KINASE; TRANSCRIPTIONAL ACTIVITY; GENE-EXPRESSION; RECEPTOR-BETA; ZINC-FINGER; IN-VIVO; ANTIINFLAMMATORY ACTION; CARDIOVASCULAR-SYSTEM AB Glucocorticoids are essential steroid hormones secreted from the adrenal gland in response to stress. Since their discovery in the 1940s, glucocorticoids have been widely prescribed to treat inflammatory disorders and hematological cancers. In the traditional view, glucocorticoids are regarded as anti-inflammatory molecules; however, emerging evidence suggests that glucocorticoid actions are more complex than previously anticipated. The anti-inflammatory activity of glucocorticoids is attributed to the repression of pro-inflammatory genes through signal transduction by their steroid receptor, the glucocorticoid receptor (GR). The mechanisms modulating the pro-inflammatory effects of glucocorticoids are not well understood. In this review, we discuss recent findings that provide insights into the mechanism by which GR signaling can play a dual role in the regulation of the immune response. We hypothesize that these apparently opposite processes are working together to prepare the immune system to respond to a stressor (pro-inflammatory effects) and subsequently restore homeostasis (anti-inflammatory effects). Finally, we propose that determining the mechanisms which underlie the tissue-specific effects of glucocorticoids will provide an excellent tool to develop more efficient and selective glucocorticoid therapies. (C) 2014 S. Karger AG, Basel C1 [Cruz-Topete, Diana; Cidlowski, John A.] NIEHS, Lab Signal Transduct, NIH, US Dept HHS, Res Triangle Pk, NC 27709 USA. RP Cidlowski, JA (reprint author), NIEHS, Lab Signal Transduct, POB 12233, Res Triangle Pk, NC 27709 USA. EM cidlows1@niehs.nih.gov FU NIEHS Intramural Research Program of the National Institutes of Health FX We would like to apologize to those colleagues whose work we were unable to cite owing to space limitations. We would like to thank these individuals for all their work that has significantly contributed to our understanding of GR molecular actions. We also would like to thank Dr. Mahita Kadmiel, Dr. Sivapriya Ramamoorthy, Dr. Shannon Whirledge and Alyson Scoltock for their helpful input. Finally, we would like to acknowledge NIEHS arts and photography for their assistance. This work was supported by the NIEHS Intramural Research Program of the National Institutes of Health. NR 81 TC 26 Z9 27 U1 0 U2 35 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 1021-7401 EI 1423-0216 J9 NEUROIMMUNOMODULAT JI Neuroimmunomodulation PY 2015 VL 22 IS 1-2 BP 20 EP 32 DI 10.1159/000362724 PG 13 WC Endocrinology & Metabolism; Immunology; Neurosciences SC Endocrinology & Metabolism; Immunology; Neurosciences & Neurology GA AQ5PE UT WOS:000342860300003 PM 25227506 ER PT B AU Kotlyar, D Blonski, W Gorodenker, J Lichtenstein, GR AF Kotlyar, David Blonski, Wojciech Gorodenker, Joseph Lichtenstein, Gary R. BE Rubin, DT Friedman, S Farrsye, FA TI WHICH THERAPIES ARE STEROID SPARING IN CROHNIS DISEASE AND ULCERATIVE COLITIS? HOW SHOULD I MANAGE A STEROID DEPENDENT PATIENT? SO CURBSIDE CONSULTATION IN IBD, SECOND EDITION SE Curbside Consultation in Gastroenterology LA English DT Article; Book Chapter ID INFLAMMATORY-BOWEL-DISEASE; T-CELL LYMPHOMA; CORTICOSTEROIDS; RISK; IMMUNOMODULATORS; ASSOCIATION; INFLIXIMAB C1 [Kotlyar, David] NCI, Med Oncol Serv, NIH, Bethesda, MD 20892 USA. [Blonski, Wojciech; Lichtenstein, Gary R.] Hosp Univ Penn, Inflammatory Bowel Dis Program, Philadelphia, PA 19104 USA. [Gorodenker, Joseph] George Washington Univ Hosp, Washington, DC USA. RP Kotlyar, D (reprint author), NCI, Med Oncol Serv, NIH, Bethesda, MD 20892 USA. NR 14 TC 0 Z9 0 U1 0 U2 2 PU SLACK INC PI THOROFARE PA 6900 GROVE ROAD, THOROFARE, NJ 08086-9447 USA BN 978-1-61711-034-4 J9 CURB CONSULT GASTROE PY 2015 BP 63 EP 66 PG 4 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA BB0KI UT WOS:000340342700014 ER PT J AU Baumert, J Huang, J McKnight, B Sabater-Lleal, M Steri, M Chu, AY Trompet, S Lopez, LM Fornage, M Teumer, A Tang, WH Rudnicka, AR Malarstig, A Hottenga, JJ Kavousi, M Lahti, J Tanaka, T Hayward, C Huffman, JE Morange, PE Rose, LM Basu, S Rumley, A Stott, DJ Buckley, BM de Craen, AJM Sanna, S Masala, M Biffar, R Homuth, G Silveira, A Sennblad, B Goel, A Watkins, H Muller-Nurasyid, M Ruckerl, R Taylor, K Chen, MH de Geus, EJC Hofman, A Witteman, JCM de Maat, MPM Palotie, A Davies, G Siscovick, DS Kolcic, I Wild, SH Song, J McArdle, WL Ford, I Sattar, N Schlessinger, D Grotevendt, A Franzosi, MG Illig, T Waldenberger, M Lumley, T Tofler, GH Willemsen, G Uitterlinden, AG Rivadeneira, F Raikkonen, K Chasman, DI Folsom, AR Lowe, GD Westendorp, RGJ Slagboom, PE Cucca, F Wallaschofski, H Strawbridge, RJ Seedorf, U Koenig, W Bis, JC Mukamal, KJ van Dongen, J Widen, E Franco, OH Starr, JM Liu, K Ferrucci, L Polasek, O Wilson, JF Oudot-Mellakh, T Campbell, H Navarro, P Bandinelli, S Eriksson, J Boomsma, DI Dehghan, A Clarke, R Hamsten, A Boerwinkle, E Jukema, JW Naitza, S Ridker, PM Volzke, H Deary, IJ Reiner, AP Tregouet, DA O'Donnell, CJ Strachan, DP Peters, A Smith, NL AF Baumert, Jens Huang, Jie McKnight, Barbara Sabater-Lleal, Maria Steri, Maristella Chu, Audrey Y. Trompet, Stella Lopez, Lorna M. Fornage, Myriam Teumer, Alexander Tang, Weihong Rudnicka, Alicja R. Maelarstig, Anders Hottenga, Jouke-Jan Kavousi, Maryam Lahti, Jari Tanaka, Toshiko Hayward, Caroline Huffman, Jennifer E. Morange, Pierre-Emmanuel Rose, Lynda M. Basu, Saonli Rumley, Ann Stott, David J. Buckley, Brendan M. de Craen, Anton J. M. Sanna, Serena Masala, Marco Biffar, Reiner Homuth, Georg Silveira, Angela Sennblad, Bengt Goel, Anuj Watkins, Hugh Mueller-Nurasyid, Martina Rueckerl, Regina Taylor, Kent Chen, Ming-Huei de Geus, Eco J. C. Hofman, Albert Witteman, Jacqueline C. M. de Maat, Moniek P. M. Palotie, Aarno Davies, Gail Siscovick, David S. Kolcic, Ivana Wild, Sarah H. Song, Jaejoon McArdle, Wendy L. Ford, Ian Sattar, Naveed Schlessinger, David Grotevendt, Anne Franzosi, Maria Grazia Illig, Thomas Waldenberger, Melanie Lumley, Thomas Tofler, Geoffrey H. Willemsen, Gonneke Uitterlinden, Andre G. Rivadeneira, Fernando Raeikkonen, Katri Chasman, Daniel I. Folsom, Aaron R. Lowe, Gordon D. Westendorp, Rudi G. J. Slagboom, P. Eline Cucca, Francesco Wallaschofski, Henri Strawbridge, Rona J. Seedorf, Udo Koenig, Wolfgang Bis, Joshua C. Mukamal, Kenneth J. van Dongen, Jenny Widen, Elisabeth Franco, Oscar H. Starr, John M. Liu, Kiang Ferrucci, Luigi Polasek, Ozren Wilson, James F. Oudot-Mellakh, Tiphaine Campbell, Harry Navarro, Pau Bandinelli, Stefania Eriksson, Johan Boomsma, Dorret I. Dehghan, Abbas Clarke, Robert Hamsten, Anders Boerwinkle, Eric Jukema, J. Wouter Naitza, Silvia Ridker, Paul M. Voezke, Henry Deary, Ian J. Reiner, Alexander P. Tregoueet, David-Alexandre O'Donnell, Christopher J. Strachan, David P. Peters, Annette Smith, Nicholas L. TI No Evidence for Genome-Wide Interactions on Plasma Fibrinogen by Smoking, Alcohol Consumption and Body Mass Index: Results from Meta-Analyses of 80,607 Subjects SO PLOS ONE LA English DT Article ID INDIVIDUAL PARTICIPANT METAANALYSIS; CARDIOVASCULAR-DISEASE RISK; CIRCULATING FIBRINOGEN; MYOCARDIAL-INFARCTION; LUNG-CANCER; INFLAMMATORY MARKERS; CIGARETTE-SMOKING; GENETIC-VARIATION; ASSOCIATION; LOCI AB Plasma fibrinogen is an acute phase protein playing an important role in the blood coagulation cascade having strong associations with smoking, alcohol consumption and body mass index (BMI). Genome-wide association studies (GWAS) have identified a variety of gene regions associated with elevated plasma fibrinogen concentrations. However, little is yet known about how associations between environmental factors and fibrinogen might be modified by genetic variation. Therefore, we conducted large-scale meta-analyses of genome-wide interaction studies to identify possible interactions of genetic variants and smoking status, alcohol consumption or BMI on fibrinogen concentration. The present study included 80,607 subjects of European ancestry from 22 studies. Genome-wide interaction analyses were performed separately in each study for about 2.6 million single nucleotide polymorphisms (SNPs) across the 22 autosomal chromosomes. For each SNP and risk factor, we performed a linear regression under an additive genetic model including an interaction term between SNP and risk factor. Interaction estimates were meta-analysed using a fixed-effects model. No genome-wide significant interaction with smoking status, alcohol consumption or BMI was observed in the meta-analyses. The most suggestive interaction was found for smoking and rs10519203, located in the LOC123688 region on chromosome 15, with a p value of 6.2x10(-8). This large genome-wide interaction study including 80,607 participants found no strong evidence of interaction between genetic variants and smoking status, alcohol consumption or BMI on fibrinogen concentrations. Further studies are needed to yield deeper insight in the interplay between environmental factors and gene variants on the regulation of fibrinogen concentrations. C1 [Baumert, Jens; Rueckerl, Regina; Peters, Annette] Helmholtz Zentrum Munchen, Inst Epidemiol 2, German Res Ctr Environm Hlth, Neuherberg, Germany. [Huang, Jie] NHLBI, Framingham Heart Study, Framingham, MA USA. [Huang, Jie] NHLBI, Div Intramural Res, Bethesda, MD 20892 USA. [Huang, Jie] Wellcome Trust Sanger Inst, Dept Human Genet, Cambridge, England. [McKnight, Barbara] Univ Washington, Dept Biostat, Seattle, WA 98195 USA. [Sabater-Lleal, Maria; Maelarstig, Anders; Silveira, Angela; Sennblad, Bengt; Strawbridge, Rona J.; Hamsten, Anders] Karolinska Univ Hosp Solna, Karolinska Inst, Dept Med, Cardiovasc Genet & Genom Grp,Atherosclerosis Res, Stockholm, Sweden. [Steri, Maristella; Sanna, Serena; Masala, Marco; Cucca, Francesco; Naitza, Silvia] CNR, Ist Ric Genet & Biomed, Cagliari, Italy. [Chu, Audrey Y.; Rose, Lynda M.] Brigham & Womens Hosp, Div Prevent Med, Boston, MA 02115 USA. [Trompet, Stella; Jukema, J. Wouter] Leiden Univ, Med Ctr, Dept Cardiol, Leiden, Netherlands. [Trompet, Stella; de Craen, Anton J. M.; Westendorp, Rudi G. J.] Leiden Univ, Med Ctr, Dept Gerontol & Geriatr, Leiden, Netherlands. [Lopez, Lorna M.; Davies, Gail; Deary, Ian J.] Univ Edinburgh, Dept Psychol, Edinburgh, Midlothian, Scotland. [Lopez, Lorna M.; Davies, Gail; Starr, John M.; Deary, Ian J.; Reiner, Alexander P.] Univ Edinburgh, Ctr Cognit Ageing & Cognit Epidemiol, Edinburgh, Midlothian, Scotland. [Fornage, Myriam] Univ Texas Hlth Sci Ctr Houston, Brown Fdn Inst Mol Med, Div Epidemiol, Sch Publ Hlth, Houston, TX 77030 USA. [Teumer, Alexander; Homuth, Georg] Ernst Moritz Arndt Univ Greifswald, Interfac Inst Genet & Funct Genom, Greifswald, Germany. [Tang, Weihong; Folsom, Aaron R.] Univ Minnesota, Div Epidemiol & Community Hlth, Minneapolis, MN USA. [Rudnicka, Alicja R.; Strachan, David P.] Univ London, Div Populat Hlth Sci & Educ, London, England. [Hottenga, Jouke-Jan; Willemsen, Gonneke; van Dongen, Jenny; Boomsma, Dorret I.] Vrije Univ Amsterdam, Dept Biol Psychol, Amsterdam, Netherlands. [Hottenga, Jouke-Jan; Willemsen, Gonneke; van Dongen, Jenny; Boomsma, Dorret I.] Vrije Univ Amsterdam Med Ctr, EMGO Inst, Amsterdam, Netherlands. [Kavousi, Maryam; Hofman, Albert; Witteman, Jacqueline C. M.; Uitterlinden, Andre G.; Franco, Oscar H.; Dehghan, Abbas] Erasmus MC, Dept Epidemiol, Rotterdam, Netherlands. [Kavousi, Maryam; Hofman, Albert; Witteman, Jacqueline C. M.; Uitterlinden, Andre G.; Franco, Oscar H.; Dehghan, Abbas] NCHA, NGI, Rotterdam, Netherlands. [Lahti, Jari; Raeikkonen, Katri] Univ Helsinki, Inst Behav Sci, Helsinki, Finland. [Lahti, Jari; Eriksson, Johan] Folkhalsan Res Ctr, Helsinki, Finland. [Tanaka, Toshiko; Ferrucci, Luigi] NIA, Translat Gerontol Branch, Baltimore, MD 21224 USA. [Hayward, Caroline; Huffman, Jennifer E.; Navarro, Pau] Western Gen Hosp, MRC Human Genet Unit, Inst Genet & Mol Med, Edinburgh EH4 2XU, Midlothian, Scotland. [Morange, Pierre-Emmanuel] Aix Marseille Univ, INSERM, UMR S 1062, Marseille, France. [Basu, Saonli; Song, Jaejoon] Univ Minnesota, Div Biostat, Minneapolis, MN USA. [Rumley, Ann] Univ Glasgow, Div Cardiovasc & Med Sci, Glasgow, Lanark, Scotland. [Stott, David J.] Univ Glasgow, Fac Med, Inst Cardiovasc & Med Sci, Glasgow, Lanark, Scotland. [Buckley, Brendan M.] Natl Univ Ireland Univ Coll Cork, Dept Pharmacol & Therapeut, Cork, Ireland. [Biffar, Reiner] Univ Med Greifswald, Dept Prosthet Dent Gerostomatol & Dent Mat, Greifswald, Germany. [Sennblad, Bengt] Karolinska Inst, Sci Life Lab, Stockholm, Sweden. [Goel, Anuj; Watkins, Hugh] Univ Oxford, John Radcliffe Hosp, Dept Cardiovasc Med, Oxford OX3 9DU, England. [Goel, Anuj; Watkins, Hugh] Univ Oxford, Dept Cardiovasc Med, Wellcome Trust Ctr Human Genet, Oxford, England. [Mueller-Nurasyid, Martina] German Res Ctr Environm Hlth, Helmholtz Zentrum Munchen, Inst Genet Epidemiol, Neuherberg, Germany. [Mueller-Nurasyid, Martina] Univ Munich, Inst Med Informat Biometry & Epidemiol, Chair Genet Epidemiol, Munich, Germany. [Mueller-Nurasyid, Martina] Univ Munich, Dept Med 1, Univ Hosp Grosshadern, Munich, Germany. [Rueckerl, Regina] Univ Augsburg, ESC Environm Sci Ctr, D-86159 Augsburg, Germany. [Taylor, Kent] Cedars Sinai Med Ctr, Inst Med Genet, Los Angeles, CA 90048 USA. [Chen, Ming-Huei] Boston Univ, Dept Biostat, Boston, MA 02215 USA. [de Geus, Eco J. C.; de Maat, Moniek P. M.] Erasmus MC, Dept Haematol, Rotterdam, Netherlands. [Palotie, Aarno; Widen, Elisabeth] Wellcome Trust Sanger Inst, Cambridge, England. [Palotie, Aarno] Univ Helsinki, Inst Mol Med Finland FIMM, Helsinki, Finland. [Palotie, Aarno; O'Donnell, Christopher J.; Smith, Nicholas L.] Univ Helsinki, Dept Med Genet, Helsinki, Finland. [Palotie, Aarno; O'Donnell, Christopher J.; Smith, Nicholas L.] Univ Cent Hosp, Helsinki, Finland. [Siscovick, David S.; Polasek, Ozren] Univ Washington, Dept Epidemiol, Seattle, WA 98195 USA. [Kolcic, Ivana; Wilson, James F.; Campbell, Harry] Univ Split, Sch Med, Dept Publ Hlth, Split, Croatia. [Wild, Sarah H.] Univ Edinburgh, Ctr Populat Hlth Sci, Edinburgh, Midlothian, Scotland. [McArdle, Wendy L.] Univ Bristol, Sch Social & Community Med, Bristol, Avon, England. [Ford, Ian] Univ Glasgow, Robertson Ctr Biostat, Glasgow, Lanark, Scotland. [Sattar, Naveed] BHF Glasgow Cardiovasc Res Ctr, Fac Med, Glasgow, Lanark, Scotland. [Schlessinger, David; Wallaschofski, Henri] NIA, Intramural Res Program, Baltimore, MD 21224 USA. [Grotevendt, Anne] Univ Med Greifswald, Inst Clin Chem & Lab Med, Greifswald, Germany. [Franzosi, Maria Grazia] IRCCS Ist Ric Farmacol Mario Negri, Dept Cardiovasc Res, Milan, Italy. [Illig, Thomas; Waldenberger, Melanie] German Res Ctr Environm Hlth, Helmholtz Zentrum Munchen, Res Unit Mol Epidemiol, Neuherberg, Germany. [Illig, Thomas] Hannover Med Sch, Hannover Unified Biobank, Hannover, Germany. [Lumley, Thomas] Univ Auckland, Dept Stat, Auckland 1, New Zealand. [Tofler, Geoffrey H.] Univ Sydney, Royal N Shore Hosp, Sydney, NSW 2006, Australia. [Uitterlinden, Andre G.] Erasmus MC, Dept Internal Med, Rotterdam, Netherlands. [Rivadeneira, Fernando; Chasman, Daniel I.] Brigham & Womens Hosp, Div Prevent Med, Div Genet, Boston, MA 02115 USA. [Rivadeneira, Fernando; Chasman, Daniel I.] Harvard Univ, Sch Med, Boston, MA USA. [Lowe, Gordon D.] Univ Glasgow, Inst Cardiovasc & Med Sci, Glasgow, Lanark, Scotland. Leiden Univ, Dept Mol Epidemiol, Med Ctr, Leiden, Netherlands. [Wallaschofski, Henri] DZHK German Ctr Cardiovasc Res, Greifswald, Germany. [Seedorf, Udo] Univ Munster, Leibniz Inst Arterioskleroseforsch, Munster, Germany. [Koenig, Wolfgang] Univ Ulm, Dept Internal Med Cardiol 2, Med Ctr, D-89069 Ulm, Germany. [Bis, Joshua C.] Univ Washington, Dept Med, Cardiovasc Hlth Res Unit, Seattle, WA USA. [Mukamal, Kenneth J.] Harvard Univ, Sch Med, Boston, MA USA. [Mukamal, Kenneth J.] Beth Israel Deaconess Med Ctr, Div Gen Med & Primary Care, Boston, MA 02215 USA. [Starr, John M.] Univ Edinburgh, Alzheimer Scotland Dementia Res Ctr, Edinburgh, Midlothian, Scotland. [Liu, Kiang] Northwestern Univ, Dept Prevent Med, Sch Med, Chicago, IL 60611 USA. [Oudot-Mellakh, Tiphaine; Tregoueet, David-Alexandre] INSERM, UMRS 1166, Paris, France. [Oudot-Mellakh, Tiphaine; Tregoueet, David-Alexandre] Univ Paris 06, Univ Sorbonne, UMRS 1166, Team Genom & Pathophysiol Cardiovasc Dis, Paris, France. [Oudot-Mellakh, Tiphaine; Tregoueet, David-Alexandre] ICAN Inst Cardiometabolism & Nutr, Paris, France. [Bandinelli, Stefania] Azienda Sanitaria Firenze ASF, Geriatr Unit, Florence, Italy. [Eriksson, Johan] Natl Inst Hlth & Welf, Helsinki, Finland. [Eriksson, Johan] Univ Helsinki, Dept Gen Practice & Primary Hlth Care, Helsinki, Finland. [Eriksson, Johan] Univ Helsinki, Cent Hosp, Unit Gen Practice, Helsinki, Finland. [Clarke, Robert] Univ Oxford, Clin Trial Serv Unit, Oxford, England. [Boerwinkle, Eric] Univ Texas Hlth Sci Ctr Houston, Human Genet Ctr & Inst Mol Med, Houston, TX 77030 USA. [Jukema, J. Wouter] Durrer Ctr Cardiogenet Res, Amsterdam, Netherlands. [Jukema, J. Wouter] Interuniv Cardiol Inst Netherlands, Utrecht, Netherlands. [Ridker, Paul M.] Brigham & Womens Hosp, Div Cardiol, Div Prevent Med, Boston, MA 02115 USA. [Ridker, Paul M.] Harvard Univ, Sch Med, Boston, MA USA. [Voezke, Henry] Univ Med Greifswald, Inst Community Med, Greifswald, Germany. [Peters, Annette] DZHK German Ctr Cardiovascr Res, Munich, Germany. [Smith, Nicholas L.] Grp Hlth Cooperat Puget Sound, Grp Hlth Res Inst, Seattle, WA USA. [Smith, Nicholas L.] Vet Affairs Off Res & Dev, Seattle Epidemiol Res & Informat Ctr, Seattle, WA USA. RP Peters, A (reprint author), Helmholtz Zentrum Munchen, Inst Epidemiol 2, German Res Ctr Environm Hlth, Neuherberg, Germany. EM peters@helmholtz-muenchen.de; nlsmith@u.washington.edu RI Wilson, James F/A-5704-2009; Naitza, Silvia/D-5620-2017; Polasek, Ozren/B-6002-2011; Rivadeneira, Fernando/O-5385-2015; Peters, Annette/A-6117-2011; Tregouet, David-Alexandre/E-3961-2016; Kolcic, Ivana/E-2713-2017; Slagboom, P. Eline/R-4790-2016 OI Steri, Anna Maristella/0000-0001-5869-3872; Watkins, Hugh/0000-0002-5287-9016; Sabater Lleal, Maria/0000-0002-0128-379X; Lahti, Jari/0000-0002-4310-5297; de Geus, Eco/0000-0001-6022-2666; Dehghan, Abbas/0000-0001-6403-016X; Wilson, James F/0000-0001-5751-9178; Polasek, Ozren/0000-0002-5765-1862; Rivadeneira, Fernando/0000-0001-9435-9441; Kolcic, Ivana/0000-0001-7918-6052; Strawbridge, Rona/0000-0001-8506-3585; Navarro, Pau/0000-0001-5576-8584; sanna, serena/0000-0002-3768-1749; Slagboom, P. Eline/0000-0002-2875-4723 FU National Heart, Lung and Blood Institute's Framingham Heart Study [N01-HC-25195]; Affymetrix, Inc [N02-HL-6-4278]; Bristol-Myers Squibb; AXA Research Fund; Nestle Nutrition (Nestec Ltd); Metagenics Inc; AXA; Siemens Healthcare, Erlangen, Germany; Federal State of Mecklenburg FX The Framingham Heart Study (FHS) was supported by the National Heart, Lung and Blood Institute's Framingham Heart Study (Contract No. N01-HC-25195) and its contract with Affymetrix, Inc for genotyping services (Contract No. N02-HL-6-4278). The PROSPER/PHASE study was supported by an investigator initiated grant obtained from Bristol-Myers Squibb. Dr. Kavousi is supported by AXA Research Fund. Oscar H. Franco works in ErasmusAGE, a center for aging research across the life course funded by Nestle Nutrition (Nestec Ltd), Metagenics Inc, and AXA. Part of the SHIP study was funded by a joint grant from Siemens Healthcare, Erlangen, Germany and the Federal State of Mecklenburg NR 33 TC 2 Z9 2 U1 3 U2 17 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA SN 1932-6203 J9 PLOS ONE JI PLoS One PD DEC 31 PY 2014 VL 9 IS 12 AR e111156 DI 10.1371/journal.pone.0111156 PG 18 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA AX7UC UT WOS:000347119100003 PM 25551457 ER PT J AU Covo, S Chiou, E Gordenin, DA Resnick, MA AF Covo, Shay Chiou, Eric Gordenin, Dmitry A. Resnick, Michael A. TI Suppression of Allelic Recombination and Aneuploidy by Cohesin Is Independent of Chk1 in Saccharomyces cerevisiae SO PLOS ONE LA English DT Article ID SISTER-CHROMATID COHESION; DOUBLE-STRAND BREAKS; DNA-DAMAGE RESPONSE; S-PHASE; REPAIR; ECO1; AMPLIFICATION; ESTABLISHMENT; CONDENSATION; CHECKPOINT AB Sister chromatid cohesion (SCC), which is established during DNA replication, ensures genome stability. Establishment of SCC is inhibited in G2. However, this inhibition is relived and SCC is established as a response to DNA damage, a process known as Damage Induced Cohesion (DIC). In yeast, Chk1, which is a kinase that functions in DNA damage signal transduction, is considered an activator of SCC through DIC. Nonetheless, here we show that, unlike SCC mutations, loss of CHK1 did not increase spontaneous or damage-induced allelic recombination or aneuploidy. We suggest that Chk1 has a redundant role in the control of DIC or that DIC is redundant for maintaining genome stability. C1 [Covo, Shay; Chiou, Eric; Gordenin, Dmitry A.; Resnick, Michael A.] NIEHS, Mol Genet Lab, Res Triangle Pk, NC 27709 USA. RP Covo, S (reprint author), Hebrew Univ Jerusalem, Dept Plant Pathol & Microbiol, Robert H Smith Fac Agr, IL-76100 Rehovot, Israel. EM shay.covo@mail.huji.ac.il FU Intramural Research Program of the National Institute of Environmental Health Sciences (NIEHS NIH, DHHS) [1Z01ES065073] FX This work was supported by the Intramural Research Program of the National Institute of Environmental Health Sciences (NIEHS NIH, DHHS) under project 1Z01ES065073 to MAR. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 27 TC 2 Z9 2 U1 1 U2 6 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA SN 1932-6203 J9 PLOS ONE JI PLoS One PD DEC 31 PY 2014 VL 9 IS 12 AR e113435 DI 10.1371/journal.pone.0113435 PG 10 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA AX7UC UT WOS:000347119100006 PM 25551702 ER PT J AU Shebl, FM Hsing, AW Park, Y Hollenbeck, AR Chu, LW Meyer, TE Koshiol, J AF Shebl, Fatma M. Hsing, Ann W. Park, Yikyung Hollenbeck, Albert R. Chu, Lisa W. Meyer, Tamra E. Koshiol, Jill TI Non-Steroidal Anti-Inflammatory Drugs Use Is Associated with Reduced Risk of Inflammation-Associated Cancers: NIH-AARP Study SO PLOS ONE LA English DT Article ID PREVENT COLORECTAL ADENOMAS; UPPER AERODIGESTIVE TRACT; LONG-TERM USE; ENDOMETRIAL CANCER; LARGE COHORT; ASPIRIN USE; GASTRIC-CANCER; LUNG-CANCER; NSAID USE; HEPATOCELLULAR-CARCINOMA AB Background: Chronic inflammation has been linked to cancers, and use of nonsteroidal anti-inflammatory drugs (NSAIDs) has been associated with reduced risk of several cancers. To further refine the magnitude of NSAID-related associations, in particular for cancers related to inflammation, such as alcohol-, infection-, obesity-, and smoking-related cancers, as well as for less common cancers, we evaluated the use of NSAIDs and cancer risk in a very large cohort. We used propensity scores to account for potential selection bias and hypothesized that NSAID use is associated with decreased cancer incidence. Methods: We conducted a prospective study among 314,522 participants in the NIH-AARP Diet and Health Study. Individuals who completed the lifestyle questionnaire, which included NSAID use, in 1996-1997 were followed through 2006. Information on cancer incidence was ascertained by linking to cancer registries and vital status databases. Findings: During 2,715,994 person-years of follow-up (median 10.1 person-years), there were 51,894 incident cancers. Compared with non-users of NSAIDs, individuals who reported use in the 12 months prior to interview had a significantly lower risk of all inflammation-related cancer, alcohol-related, infection-related, obesity-related, and smoking-related cancers [hazard ratio (HR) (95% CI)) 0.90 (0.87-0.93), 0.80 (0.74-0.85), 0.82 (0.78-0.87), 0.88 (0.84-0.92), and 0.88 (0.85-0.92) respectively)]. Conclusions: After accounting for potential selection bias, our data showed an inverse association between NSAID use and alcohol-related, infection-related, obesity-related, and smoking-related cancers and support the hypothesis that inflammation is related to an increased risk of certain cancers. C1 [Shebl, Fatma M.; Hsing, Ann W.; Park, Yikyung; Meyer, Tamra E.; Koshiol, Jill] NCI, Div Canc Epidemiol & Genet, NIH, Dept Human Hlth & Serv, Rockville, MD USA. [Hollenbeck, Albert R.] AARP, Washington, DC USA. [Chu, Lisa W.] Canc Prevent Inst Calif, Fremont, CA USA. [Chu, Lisa W.] Stanford Canc Inst, Palo Alto, CA USA. RP Shebl, FM (reprint author), Yale Univ, Dept Chron Dis Epidemiol, Sch Publ Hlth, New Haven, CT 06520 USA. EM fatma.shebl@yale.edu FU Intramural Research Program of the NIH, National Cancer Institute FX This research was supported by the Intramural Research Program of the NIH, National Cancer Institute. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 84 TC 8 Z9 8 U1 0 U2 22 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA SN 1932-6203 J9 PLOS ONE JI PLoS One PD DEC 31 PY 2014 VL 9 IS 12 AR e114633 DI 10.1371/journal.pone.0114633 PG 18 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA AX7UC UT WOS:000347119100013 PM 25551641 ER PT J AU Kuchenbaecker, KB Neuhausen, SL Robson, M Barrowdale, D McGuffog, L Mulligan, AM Andrulis, IL Spurdle, AB Schmidt, MK Schmutzler, RK Engel, C Wappenschmidt, B Nevanlinna, H Thomassen, M Southey, M Radice, P Ramus, SJ Domchek, SM Nathanson, KL Lee, A Healey, S Nussbaum, RL Rebbeck, TR Arun, BK James, P Karlan, BY Lester, J Cass, I Terry, MB Daly, MB Goldgar, DE Buys, SS Janavicius, R Tihomirova, L Tung, N Dorfling, CM van Rensburg, EJ Steele, L Hansen, TVO Ejlertsen, B Gerdes, AM Nielsen, FC Dennis, J Cunningham, J Hart, S Slager, S Osorio, A Benitez, J Duran, M Weitzel, JN Tafur, I Hander, M Peterlongo, P Manoukian, S Peissel, B Roversi, G Scuvera, G Bonanni, B Mariani, P Volorio, S Dolcetti, R Varesco, L Papi, L Tibiletti, MG Giannini, G Fostira, F Konstantopoulou, I Garber, J Hamann, U Donaldson, A Brewer, C Foo, C Evans, DG Frost, D Eccles, D Douglas, F Brady, A Cook, J Tischkowitz, M Adlard, J Barwell, J Ong, KR Walker, L Izatt, L Side, LE Kennedy, MJ Rogers, MT Porteous, ME Morrison, PJ Platte, R Eeles, R Davidson, R Hodgson, S Ellis, S Godwin, AK Rhiem, K Meindl, A Ditsch, N Arnold, N Plendl, H Niederacher, D Sutter, C Steinemann, D Bogdanova-Markov, N Kast, K Varon-Mateeva, R Wang-Gohrke, S Gehrig, A Markiefka, B Buecher, B Lefol, C Stoppa-Lyonnet, D Rouleau, E Prieur, F Damiola, F Barjhoux, L Faivre, L Longy, M Sevenet, N Sinilnikova, OM Mazoyer, S Bonadona, V Caux-Moncoutier, V Isaacs, C Van Maerken, T Claes, K Piedmonte, M Andrews, L Hays, J Rodriguez, GC Caldes, T de la Hoya, M Khan, S Hogervorst, FBL Aalfs, CM de Lange, JL Meijers-Heijboer, HEJ van der Hout, AH Wijnen, JT van Roozendaal, KEP Mensenkamp, AR van den Ouweland, AMW van Deurzen, CHM van der Luijt, RB Olah, E Diez, O Lazaro, C Blanco, I Teule, A Menendez, M Jakubowska, A Lubinski, J Cybulski, C Gronwald, J Jaworska-Bieniek, K Durda, K Arason, A Maugard, C Soucy, P Montagna, M Agata, S Teixeira, MR Olswold, C Lindor, N Pankratz, VS Hallberg, E Wang, XS Szabo, CI Vijai, J Jacobs, L Corines, M Lincoln, A Berger, A Fink-Retter, A Singer, CF Rappaport, C Kaulich, DG Pfeiler, G Tea, MK Phelan, CM Mai, PL Greene, MH Rennert, G Imyanitov, EN Glendon, G Toland, AE Bojesen, A Pedersen, IS Jensen, UB Caligo, MA Friedman, E Berger, R Laitman, Y Rantala, J Arver, B Loman, N Borg, A Ehrencrona, H Olopade, OI Simard, J Easton, DF Chenevix-Trench, G Offit, K Couch, FJ Antoniou, AC AF Kuchenbaecker, Karoline B. Neuhausen, Susan L. Robson, Mark Barrowdale, Daniel McGuffog, Lesley Mulligan, Anna Marie Andrulis, Irene L. Spurdle, Amanda B. Schmidt, Marjanka K. Schmutzler, Rita K. Engel, Christoph Wappenschmidt, Barbara Nevanlinna, Heli Thomassen, Mads Southey, Melissa Radice, Paolo Ramus, Susan J. Domchek, Susan M. Nathanson, Katherine L. Lee, Andrew Healey, Sue Nussbaum, Robert L. Rebbeck, Timothy R. Arun, Banu K. James, Paul Karlan, Beth Y. Lester, Jenny Cass, Ilana Terry, Mary Beth Daly, Mary B. Goldgar, David E. Buys, Saundra S. Janavicius, Ramunas Tihomirova, Laima Tung, Nadine Dorfling, Cecilia M. van Rensburg, Elizabeth J. Steele, Linda Hansen, Thomas V. O. Ejlertsen, Bent Gerdes, Anne-Marie Nielsen, Finn C. Dennis, Joe Cunningham, Julie Hart, Steven Slager, Susan Osorio, Ana Benitez, Javier Duran, Mercedes Weitzel, Jeffrey N. Tafur, Isaac Hander, Mary Peterlongo, Paolo Manoukian, Siranoush Peissel, Bernard Roversi, Gaia Scuvera, Giulietta Bonanni, Bernardo Mariani, Paolo Volorio, Sara Dolcetti, Riccardo Varesco, Liliana Papi, Laura Tibiletti, Maria Grazia Giannini, Giuseppe Fostira, Florentia Konstantopoulou, Irene Garber, Judy Hamann, Ute Donaldson, Alan Brewer, Carole Foo, Claire Evans, D. Gareth Frost, Debra Eccles, Diana Douglas, Fiona Brady, Angela Cook, Jackie Tischkowitz, Marc Adlard, Julian Barwell, Julian Ong, Kai-ren Walker, Lisa Izatt, Louise Side, Lucy E. Kennedy, M. John Rogers, Mark T. Porteous, Mary E. Morrison, Patrick J. Platte, Radka Eeles, Ros Davidson, Rosemarie Hodgson, Shirley Ellis, Steve Godwin, Andrew K. Rhiem, Kerstin Meindl, Alfons Ditsch, Nina Arnold, Norbert Plendl, Hansjoerg Niederacher, Dieter Sutter, Christian Steinemann, Doris Bogdanova-Markov, Nadja Kast, Karin Varon-Mateeva, Raymonda Wang-Gohrke, Shan Gehrig, Andrea Markiefka, Birgid Buecher, Bruno Lefol, Cedrick Stoppa-Lyonnet, Dominique Rouleau, Etienne Prieur, Fabienne Damiola, Francesca Barjhoux, Laure Faivre, Laurence Longy, Michel Sevenet, Nicolas Sinilnikova, Olga M. Mazoyer, Sylvie Bonadona, Valerie Caux-Moncoutier, Virginie Isaacs, Claudine Van Maerken, Tom Claes, Kathleen Piedmonte, Marion Andrews, Lesley Hays, John Rodriguez, Gustavo C. Caldes, Trinidad de la Hoya, Miguel Khan, Sofia Hogervorst, Frans B. L. Aalfs, Cora M. de lange, J. L. Meijers-Heijboer, Hanne E. J. van der Hout, Annemarie H. Wijnen, Juul T. van Roozendaal, K. E. P. Mensenkamp, Arjen R. van den Ouweland, Ans M. W. van Deurzen, Carolien H. M. van der Luijt, Rob B. Olah, Edith Diez, Orland Lazaro, Conxi Blanco, Ignacio Teule, Alex Menendez, Mireia Jakubowska, Anna Lubinski, Jan Cybulski, Cezary Gronwald, Jacek Jaworska-Bieniek, Katarzyna Durda, Katarzyna Arason, Adalgeir Maugard, Christine Soucy, Penny Montagna, Marco Agata, Simona Teixeira, Manuel R. Olswold, Curtis Lindor, Noralane Pankratz, Vernon S. Hallberg, Emily Wang, Xianshu Szabo, Csilla I. Vijai, Joseph Jacobs, Lauren Corines, Marina Lincoln, Anne Berger, Andreas Fink-Retter, Anneliese Singer, Christian F. Rappaport, Christine Kaulich, Daphne Gschwantler Pfeiler, Georg Tea, Muy-Kheng Phelan, Catherine M. Mai, Phuong L. Greene, Mark H. Rennert, Gad Imyanitov, Evgeny N. Glendon, Gord Toland, Amanda Ewart Bojesen, Anders Pedersen, Inge Sokilde Jensen, Uffe Birk Caligo, Maria A. Friedman, Eitan Berger, Raanan Laitman, Yael Rantala, Johanna Arver, Brita Loman, Niklas Borg, Ake Ehrencrona, Hans Olopade, Olufunmilayo I. Simard, Jacques Easton, Douglas F. Chenevix-Trench, Georgia Offit, Kenneth Couch, Fergus J. Antoniou, Antonis C. CA Breast Canc Family Registry EMBRACE Study GEMO Study Collaborators HEBON KConFab Investigators CIMBA TI Associations of common breast cancer susceptibility alleles with risk of breast cancer subtypes in BRCA1 and BRCA2 mutation carriers SO BREAST CANCER RESEARCH LA English DT Article AB Introduction: More than 70 common alleles are known to be involved in breast cancer (BC) susceptibility, and several exhibit significant heterogeneity in their associations with different BC subtypes. Although there are differences in the association patterns between BRCA1 and BRCA2 mutation carriers and the general population for several loci, no study has comprehensively evaluated the associations of all known BC susceptibility alleles with risk of BC subtypes in BRCA1 and BRCA2 carriers. Methods: We used data from 15,252 BRCA1 and 8,211 BRCA2 carriers to analyze the associations between approximately 200,000 genetic variants on the iCOGS array and risk of BC subtypes defined by estrogen receptor (ER), progesterone receptor (PR), human epidermal growth factor receptor 2 (HER2) and triple-negative-(TN) status; morphologic subtypes; histological grade; and nodal involvement. Results: The estimated BC hazard ratios (HRs) for the 74 known BC alleles in BRCA1 carriers exhibited moderate correlations with the corresponding odds ratios from the general population. However, their associations with ER-positive BC in BRCA1 carriers were more consistent with the ER-positive associations in the general population (intraclass correlation (ICC) = 0.61, 95% confidence interval (CI): 0.45 to 0.74), and the same was true when considering ER-negative associations in both groups (ICC = 0.59, 95% CI: 0.42 to 0.72). Similarly, there was strong correlation between the ER-positive associations for BRCA1 and BRCA2 carriers (ICC = 0.67, 95% CI: 0.52 to 0.78), whereas ER-positive associations in any one of the groups were generally inconsistent with ER-negative associations in any of the others. After stratifying by ER status in mutation carriers, additional significant associations were observed. Several previously unreported variants exhibited associations at P < 10-6 in the analyses by PR status, HER2 status, TN phenotype, morphologic subtypes, histological grade and nodal involvement. Conclusions: Differences in associations of common BC susceptibility alleles between BRCA1 and BRCA2 carriers and the general population are explained to a large extent by differences in the prevalence of ER-positive and ER-negative tumors. Estimates of the risks associated with these variants based on population-based studies are likely to be applicable to mutation carriers after taking ER status into account, which has implications for risk prediction. C1 [Kuchenbaecker, Karoline B.; Barrowdale, Daniel; McGuffog, Lesley; Dennis, Joe; Frost, Debra; Platte, Radka; Ellis, Steve; Bojesen, Anders; Easton, Douglas F.; Antoniou, Antonis C.; EMBRACE Study; CIMBA] Univ Cambridge, Dept Publ Hlth & Primary Care, Ctr Canc Genet Epidemiol, Cambridge, England. [Neuhausen, Susan L.; Steele, Linda] Beckman Res Inst City Hope, Dept Populat Sci, Duarte, CA USA. [Robson, Mark; Vijai, Joseph; Offit, Kenneth] Mem Sloan Kettering Canc Ctr, Clin Genet Res Lab, New York, NY 10021 USA. [Mulligan, Anna Marie] Univ Toronto, Dept Lab Med & Pathobiol, Toronto, ON, Canada. [Mulligan, Anna Marie] Univ Hlth Network, Lab Med Program, Toronto, ON, Canada. [Andrulis, Irene L.] Mt Sinai Hosp, Lunenfeld Tanenbaum Res Inst, Toronto, ON, Canada. [Andrulis, Irene L.] Univ Toronto, Dept Mol Genet, Toronto, ON, Canada. [Andrulis, Irene L.] Univ Toronto, Dept Lab Med & Pathobiol, Toronto, ON, Canada. [Spurdle, Amanda B.; Chenevix-Trench, Georgia] QIMR Berghofer Med Res Inst, Dept Genet & Computat Biol, Brisbane, Qld, Australia. [Schmidt, Marjanka K.] Netherlands Canc Inst, Div Psychosocial Res & Epidemiol, Amsterdam, Netherlands. [Schmutzler, Rita K.; Wappenschmidt, Barbara; Rhiem, Kerstin] Univ Hosp Cologne, Fac Med, Ctr Hereditary Breast & Ovarian Canc, Cologne, Germany. [Wappenschmidt, Barbara; Rhiem, Kerstin; Markiefka, Birgid] Univ Hosp Cologne, Fac Med, CIO, Cologne, Germany. [Schmutzler, Rita K.] Univ Cologne, CMMC, GC HBOC, Cologne, Germany. [Engel, Christoph] Univ Leipzig, Inst Med Informat Stat & Epidemiol, Leipzig, Germany. [Wappenschmidt, Barbara; Rhiem, Kerstin] Univ Cologne, CMMC, Cologne, Germany. [Nevanlinna, Heli; Khan, Sofia] Univ Helsinki, Dept Obstet & Gynecol, Helsinki, Hus, Finland. [Nevanlinna, Heli; Khan, Sofia] Univ Helsinki, Cent Hosp, HUS, Helsinki, Hus, Finland. [Thomassen, Mads] Odense Univ Hosp, Dept Clin Genet, Odense C, Denmark. [Southey, Melissa] Univ Melbourne, Genet Epidemiol Lab, Dept Pathol, Parkville, Vic, Australia. [Radice, Paolo] Fdn IRCCS Ist Nazl Tumori INT, Unit Mol Bases Genet Risk & Genet Testing, Dept Prevent & Predict Med, Milan, Italy. [Ramus, Susan J.] Univ Southern Calif, Keck Sch Med, Dept Prevent Med, Los Angeles, CA USA. [Domchek, Susan M.; Nathanson, Katherine L.] Univ Penn, Dept Med, Abramson Canc Ctr, Perelman Sch Med, Philadelphia, PA 19104 USA. [Healey, Sue] Queensland Inst Med Res, Dept Genet & Computat Biol, Herston, Qld, Australia. [Nussbaum, Robert L.] Univ Calif San Francisco, Dept Med, San Francisco, CA USA. [Nussbaum, Robert L.] Univ Calif San Francisco, Inst Human Genet, San Francisco, CA 94143 USA. [Rebbeck, Timothy R.] Univ Penn, Perelman Sch Med, Abramson Canc Ctr, Philadelphia, PA 19104 USA. [Rebbeck, Timothy R.] Univ Penn, Perelman Sch Med, Ctr Clin Epidemiol & Biostat, Philadelphia, PA 19104 USA. [Arun, Banu K.] Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA. [James, Paul] Peter MacCallum Canc Ctr, Familial Canc Ctr, Melbourne, Vic, Australia. [James, Paul] Univ Melbourne, Sir Peter MacCallum Dept Oncol, Parkville, Vic, Australia. [Karlan, Beth Y.; Lester, Jenny; Cass, Ilana] Cedars Sinai Med Ctr, Samuel Oschin Comprehens Canc Inst, Womens Canc Program, Los Angeles, CA 90048 USA. [Breast Canc Family Registry] Canc Prevent Inst Calif, Dept Epidemiol, Fremont, CA USA. [Terry, Mary Beth] Columbia Univ, Dept Epidemiol, New York, NY USA. [Daly, Mary B.] Fox Chase Canc Ctr, Philadelphia, PA 19111 USA. [Goldgar, David E.] Univ Utah, Sch Med, Dept Dermatol, Salt Lake City, UT USA. [Buys, Saundra S.] Univ Utah, Sch Med, Huntsman Canc Inst, Dept Oncol Sci, Salt Lake City, UT USA. [Janavicius, Ramunas] Vilnius Univ Hosp Santariskiu Clin, Dept Mol & Regenerat Med, Hematol Oncol & Transfus Med Ctr, Vilnius, Lithuania. [Janavicius, Ramunas] State Res Inst, Ctr Innovat Med, Vilnius, Lithuania. [Tihomirova, Laima] Latvian Biomed Res & Study Ctr, Riga, Latvia. [Tung, Nadine] Beth Israel Deaconess Med Ctr, Dept Med Oncol, Boston, MA 02215 USA. [Dorfling, Cecilia M.; van Rensburg, Elizabeth J.] Univ Pretoria, Dept Genet, Pretoria, South Africa. [Hansen, Thomas V. O.; Nielsen, Finn C.] Copenhagen Univ Hosp, Rigshosp, Ctr Genom Med, Copenhagen, Denmark. [Ejlertsen, Bent] Copenhagen Univ Hosp, Rigshosp, Dept Oncol, Copenhagen, Denmark. [Gerdes, Anne-Marie] Copenhagen Univ Hosp, Rigshosp, Dept Clin Genet, Copenhagen, Denmark. [Cunningham, Julie; Couch, Fergus J.] Mayo Clin, Dept Lab Med & Pathol, Rochester, MN USA. 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[Soucy, Penny; Simard, Jacques] Univ Laval, Quebec City, PQ, Canada. [Montagna, Marco; Agata, Simona] IRCCS, Ist Oncol Veneto, Immunol & Mol Oncol Unit, Padua, Italy. [Teixeira, Manuel R.] Portuguese Oncol Inst, Dept Genet, Oporto, Portugal. [KConFab Investigators] Peter MacCallum Canc Ctr, kConFab Kathleen Cuningham Consortium Res Familia, Melbourne, Vic, Australia. [Lindor, Noralane] Mayo Clin, Hlth Sci Res, Scottsdale, AZ USA. [Wang, Xianshu] Mayo Clin, Dept Lab Med & Pathol, Rochester, MN USA. [Szabo, Csilla I.] NHGRI, NIH, Bethesda, MD 20892 USA. [Jacobs, Lauren; Corines, Marina; Lincoln, Anne] Mem Sloan Kettering Canc Ctr, Dept Med, Clin Genet Serv, New York, NY 10021 USA. [Berger, Andreas; Fink-Retter, Anneliese; Rappaport, Christine; Kaulich, Daphne Gschwantler; Pfeiler, Georg; Tea, Muy-Kheng] Med Univ Vienna, Dept Obstet & Gynecol, Vienna, Austria. 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[Toland, Amanda Ewart] Ohio State Univ, Ctr Comprehens Canc, Dept Immunol & Med Genet, Columbus, OH 43210 USA. [Bojesen, Anders] Vejle Hosp, Dept Clin Genet, Vejle, Denmark. [Pedersen, Inge Sokilde] Aalborg Univ Hosp, Dept Biochem, Sect Mol Diagnost, Aalborg, Denmark. [Jensen, Uffe Birk] Aarhus Univ Hosp, Dept Clin Genet, Aarhus N, Denmark. [Caligo, Maria A.] Univ Pisa, Dept Lab Med, Sect Genet Oncol, Pisa, Italy. [Caligo, Maria A.] Univ Hosp Pisa, Pisa, Italy. [Friedman, Eitan; Berger, Raanan; Laitman, Yael] Sheba Med Ctr, Tel Aviv, Israel. [Rantala, Johanna] Karolinska Univ Hosp, Dept Clin Genet, Stockholm, Sweden. [Arver, Brita] Karolinska Univ Hosp, Dept Oncol, Stockholm, Sweden. [Loman, Niklas] Univ Lund Hosp, Dept Oncol, Lund, Sweden. [Borg, Ake] Lund Univ, Dept Oncol, Lund, Sweden. Uppsala Univ, Dept Immunol Genet & Pathol, Uppsala, Sweden. Univ Lund Hosp, Dept Clin Genet, Lund, Sweden. [Ehrencrona, Hans] Univ Chicago, Med Ctr, Ctr Clin Canc Genet & Global Hlth, Chicago, IL 60637 USA. [Ehrencrona, Hans] Univ Lund Hosp, Dept Clin Genet, Lund, Sweden. RP Kuchenbaecker, KB (reprint author), Univ Cambridge, Dept Publ Hlth & Primary Care, Ctr Canc Genet Epidemiol, Cambridge, England. EM kbk21@medschl.cam.ac.uk RI Giannini, Giuseppe/B-5672-2013; montagna, marco/E-2225-2012; Mensenkamp, A.R./L-4520-2015; Jansen van Rensburg, Elizabeth (Lizette)/B-9104-2011; Gronwald, Jacek/A-4576-2017; manoukian, siranoush/E-7132-2017; Peissel, Bernard/E-8187-2017; Spurdle, Amanda/A-4978-2011; Menendez Vila, Mireia/H-9981-2015; OI Giannini, Giuseppe/0000-0003-0299-4056; Blanco, Ignacio/0000-0002-7414-7481; Ramus, Susan/0000-0003-0005-7798; montagna, marco/0000-0002-4929-2150; Gronwald, Jacek/0000-0002-3643-2871; manoukian, siranoush/0000-0002-6034-7562; Peissel, Bernard/0000-0001-9233-3571; Eeles, Rosalind/0000-0002-3698-6241; Spurdle, Amanda/0000-0003-1337-7897; Barrowdale, Daniel/0000-0003-1661-3939; Dolcetti, Riccardo/0000-0003-1625-9853; Papi, Laura/0000-0003-4552-9517; Menendez Vila, Mireia/0000-0001-8050-0803; Ehrencrona, Hans/0000-0002-5589-3622; Khan, Sofia/0000-0003-4185-8882; Evans, Gareth/0000-0002-8482-5784 FU Cancer Research UK grant [C12292/A11174]; European Community's Seventh Framework Programme (COGS) [223175 (HEALTH-F2-2009-223175)]; Cancer Research UK [C12292/A11174, C1287/A10118, C1287/A 10710, C1281/A12014, C5047/A8384, C5047/A15007, C5047/A10692]; National Institutes of Health [CA128978, 5U01 CA113916, R01 CA140323]; Post-Cancer GWAS initiative (Genetic Associations and Mechanisms in Oncology (GAME-ON) initiative) [1U19 CA148537, 1U19 CA148065, 1U19 CA148112]; US Department of Defense [W81XWH-10-1-0341]; Canadian Institutes of Health Research (CIHR) for the CIHR Team in Familial Risks of Breast Cancer; Komen Foundation for the Cure; Breast Cancer Research Foundation; Ovarian Cancer Research Fund; National Cancer Institute [UM1 CA164920, RC4CA153828, CA 27469, CA 37517, CA 101165]; Lithuania (BFBOCC-LT): Research Council of Lithuania [LIG-07/2012]; LSC grant [10.0010.08]; ESF [2009/0220/1DP/1.1.1.2.0/09/APIA/VIAA/016]; Liepaja's municipal council; Cancer Association of South Africa (CANSA); Morris and Horowitz Families Endowed Professorship; NEYE Foundation; Spanish Association against Cancer [AECC08]; RTICC [06/0020/1060, FISPI12/00070]; Mutua Madrilena Foundation (FMMA); Office of the Director, National Institutes of Health; Fondazione IRCCS Istituto Nazionale Tumori; IRCCS AOU San Martino; IST Istituto Nazionale per la Ricerca sul Cancro; Italian Association for Cancer Research (AIRC); Associazione CAOS-Varese; NHMRC Program Grant; European Union (European Social Fund (ESF)); Greek national funds through Operational Program "Education and Lifelong Learning" of the National Strategic Reference Framework (NSRF); Research Funding Program of the General Secretariat for Research & Technology: ARISTEIA; DKFZ; Cancer Research UK grants [C1287/A10118, C1287/A16563, C1287/A17523, C5047/A8385]; NIHR grant; University of Kansas Cancer Center [P30 CA168524]; Kansas Bioscience Authority Eminent Scholar Program; Chancellors Distinguished Chair in Biomedical Sciences Professorship; German Cancer Aid [109076]; Center for Molecular Medicine Cologne (CMMC); Ligue National Contre le Cancer; Association "Le cancer du sein, parlons-en!" Award; Canadian Institutes of Health Research for the "CIHR Team in Familial Risks of Breast Cancer" program; National Cancer Institute; NCI Intramural Research Program; ISCIII (Spain) [RD12/00369/0006, 12/00539]; European Regional Development FEDER funds; Helsinki University Central Hospital Research Fund, Academy of Finland [266528]; Finnish Cancer Society; Sigrid Juselius Foundation; Dutch Cancer Society grants [NKI1998-1854, NKI2004-3088, NKI2007-3756]; Netherlands Organization of Scientific Research grant [NWO 91109024]; Pink Ribbon grant [110005]; BBMRI grant [NWO 184.021.007/CP46]; Hong Kong Hereditary Breast Cancer Family Registry; Dr Ellen Li Charitable Foundation, Hong Kong; Hungarian Research Grants [KTIA-OTKA CK-80745, OTKA K-112228]; Asociacion Espanola Contra el Cancer, Spanish Health Research Fund; Carlos III Health Institute; Catalan Health Institute and Autonomous Government of Catalonia; ISCIIIRETIC [RD06/0020/1051, RD12/0036/008, PI10/01422, PI10/00748, PI13/00285, 2009SGR290]; Icelandic Association "Walking for Breast Cancer Research"; Landspitali University Hospital Research Fund; Canadian Breast Cancer Research Alliance grant [019511]; Ministry of Economic Development, Innovation and Export Trade grant [PSR-SIIRI-701]; Ministero della Salute; "5 x 1000" Istituto Oncologico Veneto grant; Liga Portuguesa Contra o Cancro; National Breast Cancer Foundation; National Health and Medical Research Council (NHMRC); Queensland Cancer Fund; Cancer Councils of New South Wales, Victoria, Tasmania and South Australia; Cancer Foundation of Western Australia; NHMRC Research Fellowship scheme; National R&D Program for Cancer Control, Ministry for Health, Welfare and Family Affairs, Republic of Korea [1020350]; NIH grant [CA128978]; NCI Specialized Program of Research Excellence (SPORE) in Breast Cancer [CA116201, CA125183, R01 CA142996, 1U01 CA161032]; US Department of Defense Ovarian Cancer Idea award [W81XWH-10-1-0341]; MH CZ - DRO (MMCI) [00209805]; European Regional Development Fund; State Budget of the Czech Republic (RECAMO) [CZ. 1.05/2.1.00/03.0101]; Charles University in Prague project [UNCE204024]; Robert and Kate Niehaus Clinical Cancer Genetics Initiative [1R01 CA149429-01]; Intramural Research Program of the US National Cancer Institute, NIH; Westat (Rockville, MD, USA) [N02-CP-11019-50, N02-CP-65504]; Clalit Health Services in Israel; Israel Cancer Association; Breast Cancer Research Foundation (BCRF), New York; Russian Foundation for Basic Research [13-04-92613]; Ohio State University Comprehensive Cancer Center; ITT (Istituto Toscano Tumori) grants [2011-2013]; Ministry of Science, Technology and Innovation, Ministry of Higher Education [UM.C/HlR/MOHE/06]; Cancer Research Initiatives Foundation; Israeli Inherited breast cancer consortium; Swedish Cancer Society; Ralph and Marion Falk Medical Research Trust; Entertainment Industry Fund National Women's Cancer Research Alliance; CRUK; American Cancer Society Early Detection Professorship [SIOP-06-258-01-COUN]; [PBZ_KBN_122/P05/2004] FX The CIMBA data management and analysis are funded through Cancer Research UK grant C12292/A11174. ACA is a Senior Cancer Research UK Research Fellow. Funding for the iCOGS infrastructure came from: the European Community's Seventh Framework Programme under grant agreement 223175 (HEALTH-F2-2009-223175) (COGS), Cancer Research UK (C1287/A10118, C1287/A 10710, C12292/A11174, C1281/A12014, C5047/A8384, C5047/A15007, C5047/A10692), the National Institutes of Health (CA128978) and Post-Cancer GWAS initiative (1U19 CA148537, 1U19 CA148065 and 1U19 CA148112: the Genetic Associations and Mechanisms in Oncology (GAME-ON) initiative), the US Department of Defense (W81XWH-10-1-0341), the Canadian Institutes of Health Research (CIHR) for the CIHR Team in Familial Risks of Breast Cancer, Komen Foundation for the Cure, the Breast Cancer Research Foundation, and the Ovarian Cancer Research Fund. This work was supported by grant UM1 CA164920 from the National Cancer Institute. The content of this manuscript does not necessarily reflect the views or policies of the National Cancer Institute or any of the collaborating centers in the Breast Cancer Family Registry (BCFR), nor does mention of trade names, commercial products, or organizations imply endorsement by the US government or the BCFR. This work was supported by grant UM1 CA164920 from the National Cancer Institute. The content of this article does not necessarily reflect the views or policies of the National Cancer Institute or any of the collaborating centers in the Breast Cancer Family Registry (BCFR), nor does mention of trade names, commercial products, or organizations imply endorsement by the US government or the BCFR. This work was supported by grant UM1 CA164920 from the National Cancer Institute. The content of this manuscript does not necessarily reflect the views or policies of the National Cancer Institute or any of the collaborating centers in the Breast Cancer Family Registry (BCFR), nor does mention of trade names, commercial products, or organizations imply endorsement by the US government or the BCFR. BFBOCC is partly supported by: Lithuania (BFBOCC-LT): Research Council of Lithuania grant LIG-07/2012; Latvia (BFBOCC-LV) is partly supported by LSC grant 10.0010.08 and in part by a grant from the ESF 2009/0220/1DP/1.1.1.2.0/09/APIA/VIAA/016 and Liepaja's municipal council.; BIDMC is supported by the Breast Cancer Research Foundation. BRCA-gene mutations and breast cancer in South African women (BMBSA) was supported by grants from the Cancer Association of South Africa (CANSA) to Elizabeth J van Rensburg. SLN was partially supported by the Morris and Horowitz Families Endowed Professorship. This work was supported by the NEYE Foundation. The CNIO study was supported by Spanish Association against Cancer (AECC08), RTICC 06/0020/1060 and FISPI12/00070 and Mutua Madrilena Foundation (FMMA). City of Hope Clinical Cancer Genetics Community Network and the Hereditary Cancer Research Registry, supported in part by Award Number RC4CA153828 (Principal Investigator: J Weitzel) from the National Cancer Institute and the Office of the Director, National Institutes of Health. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. Funds from Italian citizens who allocated the "5 x 1000" share of their tax payment, according to Italian laws, in support of the Fondazione IRCCS Istituto Nazionale Tumori (to SM), and of IRCCS AOU San Martino, IST Istituto Nazionale per la Ricerca sul Cancro (to LV); Italian Association for Cancer Research (AIRC) to GG; Associazione CAOS-Varese (to MGT). SH is supported by an NHMRC Program Grant (to GCT). GCT is an NHMRC Senior Principal Research Fellow. This research has been cofinanced by the European Union (European Social Fund (ESF)) and Greek national funds through the Operational Program "Education and Lifelong Learning" of the National Strategic Reference Framework (NSRF), Research Funding Program of the General Secretariat for Research & Technology: ARISTEIA, investing in knowledge society through the European Social Fund. The DKFZ study was supported by the DKFZ. EMBRACE is supported by Cancer Research UK grants C1287/A10118, C1287/A16563 and C1287/A17523. D Gareth Evans and Fiona Lalloo are supported by an NIHR grant to the Biomedical Research Centre, Manchester. The investigators at The Institute of Cancer Research and The Royal Marsden NHS Foundation Trust are supported by an NIHR grant to the Biomedical Research Centre at The Institute of Cancer Research and The Royal Marsden NHS Foundation Trust. Ros Eeles and Elizabeth Bancroft are supported by Cancer Research UK grant C5047/A8385. The authors acknowledge support from The University of Kansas Cancer Center (P30 CA168524) and the Kansas Bioscience Authority Eminent Scholar Program. AKG was funded by grants 5U01 CA113916, R01 CA140323 from the National Institutes of Health and by the Chancellors Distinguished Chair in Biomedical Sciences Professorship. The German Consortium of Hereditary Breast and Ovarian Cancer (GC-HBOC) is supported by the German Cancer Aid (grant no 109076, Rita K Schmutzler) and by the Center for Molecular Medicine Cologne (CMMC). The study was supported by the Ligue National Contre le Cancer; the Association "Le cancer du sein, parlons-en!" Award; and the Canadian Institutes of Health Research for the "CIHR Team in Familial Risks of Breast Cancer" program. Tom Van Maerken is senior clinical investigator of FWO. This study was supported by National Cancer Institute grants to the Gynecologic Oncology Group (GOG) Administrative Office and Tissue Bank (CA 27469), the GOG Statistical and Data Center (CA 37517), and GOG's Cancer Prevention and Control Committee (CA 101165). Drs Greene, Mai and Savage were supported by funding from the NCI Intramural Research Program.; HCSC was supported by a grant RD12/00369/0006 and 12/00539 from ISCIII (Spain), partially supported by European Regional Development FEDER funds. The HEBCS was financially supported by the Helsinki University Central Hospital Research Fund, Academy of Finland (266528), the Finnish Cancer Society and the Sigrid Juselius Foundation. The HEBON study is supported by the Dutch Cancer Society grants NKI1998-1854, NKI2004-3088, NKI2007-3756, the Netherlands Organization of Scientific Research grant NWO 91109024, the Pink Ribbon grant 110005 and the BBMRI grant NWO 184.021.007/CP46. HEBON thanks the registration teams of the Comprehensive Cancer Centre Netherlands and Comprehensive Centre South (together the Netherlands Cancer Registry) and PALGA (Dutch Pathology Registry) for part of the data collection. HRBCP is supported by The Hong Kong Hereditary Breast Cancer Family Registry and the Dr Ellen Li Charitable Foundation, Hong Kong.; The Hungarian Breast and Ovarian Cancer Study was supported by Hungarian Research Grants KTIA-OTKA CK-80745 and OTKA K-112228. ICO: Contract grant sponsor: Asociacion Espanola Contra el Cancer, Spanish Health Research Fund; Carlos III Health Institute; Catalan Health Institute and Autonomous Government of Catalonia. Contract grants ISCIIIRETIC RD06/0020/1051, RD12/0036/008, PI10/01422, PI10/00748, PI13/00285 and 2009SGR290. The IHCC was supported by Grant PBZ_KBN_122/P05/2004. The ILUH group was supported by the Icelandic Association "Walking for Breast Cancer Research" and by the Landspitali University Hospital Research Fund. This work was supported by the Canadian Institutes of Health Research for the "CIHR Team in Familial Risks of Breast Cancer" program, Canadian Breast Cancer Research Alliance grant 019511 and Ministry of Economic Development, Innovation and Export Trade grant PSR-SIIRI-701. IOVHBOCS is supported by Ministero della Salute and "5 x 1000" Istituto Oncologico Veneto grant. This study was in part supported by Liga Portuguesa Contra o Cancro. kConFab is supported by grants from the National Breast Cancer Foundation, the National Health and Medical Research Council (NHMRC) and by the Queensland Cancer Fund, the Cancer Councils of New South Wales, Victoria, Tasmania and South Australia, and the Cancer Foundation of Western Australia. GCT and ABS are supported by the NHMRC Research Fellowship scheme. KOHBRA is supported by a grant from the National R&D Program for Cancer Control, Ministry for Health, Welfare and Family Affairs, Republic of Korea (1020350). MAYO is supported by NIH grant CA128978, an NCI Specialized Program of Research Excellence (SPORE) in Breast Cancer (CA116201), a US Department of Defense Ovarian Cancer Idea award (W81XWH-10-1-0341) and a grant from the Breast Cancer Research Foundation. Jewish General Hospital Weekend to End Breast Cancer, Quebec Ministry of Economic Development, Innovation and Export Trade. MODSQUAD was supported by MH CZ - DRO (MMCI, 00209805) and by the European Regional Development Fund and the State Budget of the Czech Republic (RECAMO, CZ. 1.05/2.1.00/03.0101) (to LF), and by Charles University in Prague project UNCE204024 (MZ). MSKCC is supported by grants from the Breast Cancer Research Foundation and Robert and Kate Niehaus Clinical Cancer Genetics Initiative 1R01 CA149429-01. The research of MH Greene and PL Mai was supported by the Intramural Research Program of the US National Cancer Institute, NIH, and by support services contracts N02-CP-11019-50 and N02-CP-65504 with Westat (Rockville, MD, USA). NICCC is supported by Clalit Health Services in Israel. Some of its activities are supported by the Israel Cancer Association and the Breast Cancer Research Foundation (BCRF), New York. This work has been supported by the Russian Foundation for Basic Research (grant 13-04-92613).; This work was supported by grant UM1 CA164920 from the National Cancer Institute. The content of this manuscript does not necessarily reflect the views or policies of the National Cancer Institute or any of the collaborating centers in the Breast Cancer Family Registry (BCFR), nor does mention of trade names, commercial products, or organizations imply endorsement by the US government or the BCFR. OSUCCG is supported by The Ohio State University Comprehensive Cancer Center. This work was supported by the ITT (Istituto Toscano Tumori) grants 2011-2013; the Ministry of Science, Technology and Innovation, Ministry of Higher Education (UM.C/HlR/MOHE/06); and the Cancer Research Initiatives Foundation. This project was partially funded through a grant by the Israel cancer association and the funding for the Israeli Inherited breast cancer consortium.; SWE-BRCA collaborators are supported by the Swedish Cancer Society. UCHICAGO is supported by NCI Specialized Program of Research Excellence (SPORE) in Breast Cancer (CA125183), R01 CA142996, 1U01 CA161032 and by the Ralph and Marion Falk Medical Research Trust, the Entertainment Industry Fund National Women's Cancer Research Alliance and the Breast Cancer Research Foundation. OIO is an ACS Clinical Research Professor. Jonsson Comprehensive Cancer Center Foundation; Breast Cancer Research Foundation. UCSF Cancer Risk Program and Helen Diller Family Comprehensive Cancer Center. UKFOCR was supported by a project grant from CRUK to Paul Pharoah. National Institutes of Health (NIH) (R01 CA102776 and R01 CA083855; Breast Cancer Research Foundation; Susan G Komen Foundation for the cure, Basser Research Center for BRCA. Victorian Cancer Agency, Cancer Australia, National Breast Cancer Foundation. The Women's Cancer Program (WCP) at the Samuel Oschin Comprehensive Cancer Institute is funded by the American Cancer Society Early Detection Professorship (SIOP-06-258-01-COUN). NR 26 TC 4 Z9 4 U1 11 U2 15 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1465-542X EI 1465-5411 J9 BREAST CANCER RES JI Breast Cancer Res. PD DEC 31 PY 2014 VL 16 AR 3416 DI 10.1186/s13058-014-0492-9 PG 27 WC Oncology SC Oncology GA V44TY UT WOS:000209772500001 PM 25919761 ER PT J AU Kim, MK Min, DJ Wright, G Goldlust, I Annunziata, CM AF Kim, Marianne K. Min, Dong J. Wright, George Goldlust, Ian Annunziata, Christina M. TI Loss of compensatory pro-survival and anti-apoptotic modulator, IKK epsilon, sensitizes ovarian cancer cells to CHEK1 loss through an increased level of p21 SO ONCOTARGET LA English DT Article DE shRNAs; therapeutic targets; IKK epsilon; CHEK1; p21; ovarian cancer ID GROWTH ARREST; INHIBITOR; ACTIVATION; CHECKPOINT; CARCINOMA; KINASE; PHOSPHORYLATION; CISPLATIN; CHK1; P21(WAF1/CIP1) AB Ovarian cancer (OC) is extremely heterogeneous, implying that therapeutic strategies should be specifically designed based on molecular characteristics of an individual's tumor. Previously, we showed that IKK epsilon promotes invasion and metastasis in a subset of OCs. Here, we identified CHEK1 as an IKK epsilon-dependent lethal gene from shRNA kinome library screen. In subsequent pharmacological intervention studies, the co-inhibition of IKK epsilon and CHEK1 was more effective in killing OC cells than single treatment. At the molecular level, co-inhibition dramatically decreased pro-survival proteins, but increased proteins involved in DNA damage and apoptosis. IKK epsilon-knockdown increased p21 levels, while overexpression of wild-type IKK epsilon, but not a kinase dead IKK epsilon mutant decreased p21 levels. We further demonstrated that the depletion of p21 rendered OC cells more resistant to cell death induced by co-inhibition of IKK epsilon and CHEK1. In conclusion, we revealed a novel interplay between IKK epsilon, CHEK1 and p21 signaling in survival of OC. Our study provides a rationale for the clinical development of specific IKK epsilon inhibitor and for usage of IKK epsilon as an exploratory marker for resistance to CHEK1 inhibitors in the clinic. The interplay provides one potential explanation as to why very few clinical responses were achieved in patients treated with single-agent CHEK1 inhibitors. C1 [Kim, Marianne K.; Annunziata, Christina M.] NCI, Womens Malignancies Branch, Ctr Canc Res, Bethesda, MD 20892 USA. [Min, Dong J.] NCI, Transgen Oncogen & Genom Sect, Ctr Canc Res, Bethesda, MD 20892 USA. [Wright, George] NCI, Biometr Res Branch, Ctr Canc Res, Bethesda, MD 20892 USA. [Goldlust, Ian] NIH, Chem Genom Ctr, Div Preclin Innovat, Natl Ctr Adv Translat Sci, Bethesda, MD 20892 USA. RP Annunziata, CM (reprint author), NCI, Womens Malignancies Branch, Ctr Canc Res, Bethesda, MD 20892 USA. EM annunzic@mail.nih.gov RI Annunziata, Christina/L-3219-2016 OI Annunziata, Christina/0000-0003-2033-6532 FU CCR, NCI; National Institutes of Health [K99CA151746] FX This work is supported by the Intramural Research Program, CCR, NCI (C.M.A.) and National Institutes of Health Grant K99CA151746 (C.M.A.). Human kinome shRNA library was kindly provided by Dr. L. Staudt (NCI, Bethesda, MD). The barcode sequencing and target gene alignments were done at CCR-sequencing facility (NCI). NR 28 TC 4 Z9 4 U1 0 U2 6 PU IMPACT JOURNALS LLC PI ALBANY PA 6211 TIPTON HOUSE, STE 6, ALBANY, NY 12203 USA SN 1949-2553 J9 ONCOTARGET JI Oncotarget PD DEC 30 PY 2014 VL 5 IS 24 BP 1 EP 15 PG 15 WC Oncology; Cell Biology SC Oncology; Cell Biology GA AZ2AX UT WOS:000348038000021 ER PT J AU Galluzzi, L Vacchelli, E Bravo-San Pedro, JM Buque, A Senovilla, L Baracco, EE Bloy, N Castoldi, F Abastado, JP Agostinis, P Apte, RN Aranda, F Ayyoub, M Beckhove, P Blay, JY Bracci, L Caignard, A Castelli, C Cavallo, F Celis, E Cerundolo, V Clayton, A Colombo, MP Coussens, L Dhodapkar, MV Eggermont, AM Fearon, DT Fridman, WH Fucikova, J Gabrilovich, DI Galon, J Garg, A Ghiringhelli, F Giaccone, G Gilboa, E Gnjatic, S Hoos, A Hosmalin, A Jager, D Kalinski, P Karre, K Kepp, O Kiessling, R Kirkwood, JM Klein, E Knuth, A Lewis, CE Liblau, R Lotze, MT Lugli, E Mach, JP Mattei, F Mavilio, D Melero, I Melief, CJ Mittendorf, EA Moretta, L Odunsi, A Okada, H Palucka, AK Peter, ME Pienta, KJ Porgador, A Prendergast, GC Rabinovich, GA Restifo, NP Rizvi, N Sautes-Fridman, C Schreiber, H Seliger, B Shiku, H Silva-Santos, B Smyth, MJ Speiser, DE Spisek, R Srivastava, PK Talmadge, JE Tartour, E Van der Burg, SH Van den Eynde, BJ Vile, R Wagner, H Weber, JS Whiteside, TL Wolchok, JD Zitvogel, L Zou, WP Kroemer, G AF Galluzzi, Lorenzo Vacchelli, Erika Bravo-San Pedro, Jose-Manuel Buque, Aitziber Senovilla, Laura Baracco, Elisa Elena Bloy, Norma Castoldi, Francesca Abastado, Jean-Pierre Agostinis, Patrizia Apte, Ron N. Aranda, Fernando Ayyoub, Maha Beckhove, Philipp Blay, Jean-Yves Bracci, Laura Caignard, Anne Castelli, Chiara Cavallo, Federica Celis, Estaban Cerundolo, Vincenzo Clayton, Aled Colombo, Mario P. Coussens, Lisa Dhodapkar, Madhav V. Eggermont, Alexander M. Fearon, Douglas T. Fridman, Wolf H. Fucikova, Jitka Gabrilovich, Dmitry I. Galon, Jerome Garg, Abhishek Ghiringhelli, Francois Giaccone, Giuseppe Gilboa, Eli Gnjatic, Sacha Hoos, Axel Hosmalin, Anne Jaeger, Dirk Kalinski, Pawel Kaerre, Klas Kepp, Oliver Kiessling, Rolf Kirkwood, John M. Klein, Eva Knuth, Alexander Lewis, Claire E. Liblau, Roland Lotze, Michael T. Lugli, Enrico Mach, Jean-Pierre Mattei, Fabrizio Mavilio, Domenico Melero, Ignacio Melief, Cornelis J. Mittendorf, Elizabeth A. Moretta, Lorenzo Odunsi, Adekunke Okada, Hideho Palucka, Anna Karolina Peter, Marcus E. Pienta, Kenneth J. Porgador, Angel Prendergast, George C. Rabinovich, Gabriel A. Restifo, Nicholas P. Rizvi, Naiyer Sautes-Fridman, Catherine Schreiber, Hans Seliger, Barbara Shiku, Hiroshi Silva-Santos, Bruno Smyth, Mark J. Speiser, Daniel E. Spisek, Radek Srivastava, Pramod K. Talmadge, James E. Tartour, Eric Van der Burg, Sjoerd H. Van den Eynde, Benoit J. Vile, Richard Wagner, Hermann Weber, Jeffrey S. Whiteside, Theresa L. Wolchok, Jedd D. Zitvogel, Laurence Zou, Weiping Kroemer, Guido TI Classification of current anticancer immunotherapies SO ONCOTARGET LA English DT Review DE adoptive cell transfer; checkpoint blockers; dendritic cell-based interventions; DNA-based vaccines; immunostimulatory cytokines; peptide-based vaccines; oncolytic viruses; Toll-like receptor agonists ID REGULATORY T-CELLS; HUMAN DENDRITIC CELLS; NATURAL-KILLER-CELLS; COLONY-STIMULATING FACTOR; ISOLATED LIMB PERFUSION; NECROSIS-FACTOR-ALPHA; TOLL-LIKE RECEPTORS; PHASE-I TRIAL; IMMUNOSTIMULATORY MONOCLONAL-ANTIBODIES; DEPENDENT CELLULAR CYTOTOXICITY AB During the past decades, anticancer immunotherapy has evolved from a promising therapeutic option to a robust clinical reality. Many immunotherapeutic regimens are now approved by the US Food and Drug Administration and the European Medicines Agency for use in cancer patients, and many others are being investigated as standalone therapeutic interventions or combined with conventional treatments in clinical studies. Immunotherapies may be subdivided into "passive" and "active" based on their ability to engage the host immune system against cancer. Since the anticancer activity of most passive immunotherapeutics (including tumor-targeting monoclonal antibodies) also relies on the host immune system, this classification does not properly reflect the complexity of the drug-host-tumor interaction. Alternatively, anticancer immunotherapeutics can be classified according to their antigen specificity. While some immunotherapies specifically target one (or a few) defined tumor-associated antigen(s), others operate in a relatively non-specific manner and boost natural or therapy-elicited anticancer immune responses of unknown and often broad specificity. Here, we propose a critical, integrated classification of anticancer immunotherapies and discuss the clinical relevance of these approaches. C1 [Galluzzi, Lorenzo; Vacchelli, Erika; Bravo-San Pedro, Jose-Manuel; Buque, Aitziber; Senovilla, Laura; Baracco, Elisa Elena; Bloy, Norma; Castoldi, Francesca; Aranda, Fernando; Kepp, Oliver; Kroemer, Guido] Ctr Rech Cordeliers, Equipe Labellisee Pas Ligue Natl Canc 11, Paris, France. [Galluzzi, Lorenzo; Vacchelli, Erika; Bravo-San Pedro, Jose-Manuel; Buque, Aitziber; Senovilla, Laura; Baracco, Elisa Elena; Bloy, Norma; Castoldi, Francesca; Aranda, Fernando; Fridman, Wolf H.; Galon, Jerome; Kepp, Oliver; Sautes-Fridman, Catherine; Kroemer, Guido] INSERM, U1138, Paris, France. [Galluzzi, Lorenzo; Vacchelli, Erika; Bravo-San Pedro, Jose-Manuel; Buque, Aitziber; Senovilla, Laura; Baracco, Elisa Elena; Bloy, Norma; Castoldi, Francesca; Aranda, Fernando; Eggermont, Alexander M.; Zitvogel, Laurence] Gustave Roussy Canc Campus, Villejuif, France. [Galluzzi, Lorenzo; Fridman, Wolf H.; Galon, Jerome; Hosmalin, Anne; Sautes-Fridman, Catherine; Tartour, Eric; Kroemer, Guido] Univ Paris 05, Sorbonne Paris Cite, Paris, France. [Baracco, Elisa Elena; Bloy, Norma; Castoldi, Francesca] Univ Paris 11, Fac Med, Le Kremlin Bicetre, France. [Castoldi, Francesca; Fucikova, Jitka; Spisek, Radek] Sotio Ac, Prague, Czech Republic. [Abastado, Jean-Pierre] Inst Rech Int Servier, Pole Innovat Therapeut Oncol, Suresnes, France. [Agostinis, Patrizia; Garg, Abhishek] Univ Leuven, Dept Cellular & Mol Med, Cell Death Res & Therapy CDRT Lab, Leuven, Belgium. [Apte, Ron N.; Porgador, Angel] Ben Gurion Univ Negev, Fac Hlth Sci, Shraga Segal Dept Microbiol Immunol & Genet, Beer Sheva, Israel. [Aranda, Fernando] Inst Invest Biomed August Pi & Sunyer IDIBAPS, Grp Immune Receptors Innate & Adapt Syst, Barcelona, Spain. [Ayyoub, Maha] INSERM, U1102, St Herblain, France. [Ayyoub, Maha] Inst Cancerol Ouest, St Herblain, France. [Beckhove, Philipp] German Canc Res Ctr, Translat Immunol Div, Heidelberg, Germany. [Blay, Jean-Yves] CLR, Equipe 11, Lyon, France. [Blay, Jean-Yves] CRCL, Lyon, France. [Bracci, Laura; Mattei, Fabrizio] Ist Super Sanita, Dept Hematol Oncol & Mol Med, I-00161 Rome, Italy. [Caignard, Anne] INSERM, U1160, Paris, France. [Caignard, Anne] Grp Hosp St Louis Lariboisiere F Vidal, Paris, France. [Castelli, Chiara; Colombo, Mario P.] Fdn IRCCS Ist Nazl Tumori, Dept Expt Oncol & Mol Med, Unit Immunotherapy Human Tumors, Milan, Italy. [Cavallo, Federica] Univ Turin, Dept Mol Biotechnol & Hlth Sci, Ctr Mol Biotechnol, Turin, Italy. [Celis, Estaban] Georgia Regents Univ, Ctr Canc, Canc Immunol Inflammat & Tolerance Program, Augusta, GA USA. [Cerundolo, Vincenzo] Univ Oxford, Weatherall Inst Mol Med, MRC Human Immunol Unit, Oxford, England. [Clayton, Aled] Cardiff Univ, Sch Med, Inst Canc & Genet, Cardiff CF10 3AX, S Glam, Wales. [Clayton, Aled] Velindre Canc Ctr, Cardiff, S Glam, Wales. [Coussens, Lisa] Oregon Hlth & Sci Univ, Knight Canc Inst, Portland, OR 97201 USA. [Dhodapkar, Madhav V.] Yale Univ, Yale Canc Ctr, Sect Hematol & Immunobiol, New Haven, CT USA. [Fearon, Douglas T.] Cold Spring Harbor Lab, Cold Spring Harbor, NY 11724 USA. [Fridman, Wolf H.; Galon, Jerome; Sautes-Fridman, Catherine] Univ Paris 06, Paris, France. [Fridman, Wolf H.; Sautes-Fridman, Catherine] Ctr Rech Cordeliers, Equipe 13, Paris, France. [Fucikova, Jitka; Spisek, Radek] Charles Univ Prague, Fac Med 2, Dept Immunol, Prague, Czech Republic. [Fucikova, Jitka; Spisek, Radek] Charles Univ Prague, Univ Hosp Motol, Prague, Czech Republic. [Gabrilovich, Dmitry I.] Univ Penn, Dept Pathol & Lab Med, Perelman Sch Med, Philadelphia, PA USA. [Galon, Jerome] Ctr Rech Cordeliers, Lab Integrat Canc Immunol, Paris, France. [Ghiringhelli, Francois] INSERM, UMR866, Dijon, France. [Ghiringhelli, Francois] Ctr Georges Francois Leclerc, Dijon, France. [Ghiringhelli, Francois] Univ Bourgogne, Dijon, France. [Giaccone, Giuseppe] NCI, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. [Giaccone, Giuseppe] Georgetown Univ, Lombardi Comprehens Canc Ctr, Washington, DC USA. [Gilboa, Eli] Univ Miami, Miller Sch Med, Sylvester Comprehens Canc Ctr, Dept Microbiol & Immunol, Miami, FL 33136 USA. [Gnjatic, Sacha] Icahn Sch Med Mt Sinai, Tisch Canc Inst, Sect Hematol Oncol Immunol, New York, NY 10029 USA. [Hoos, Axel] GlaxoSmithKline, Canc Immunotherapy Consortium, Collegeville, PA USA. [Hosmalin, Anne] INSERM, U1016, Paris, France. [Hosmalin, Anne] CNRS, UMR8104, Paris, France. [Hosmalin, Anne] Hop Cochin, AP HP, F-75674 Paris, France. [Jaeger, Dirk] Univ Med Ctr Heidelberg, Natl Ctr Tumor Dis, Heidelberg, Germany. [Kalinski, Pawel; Lotze, Michael T.] Univ Pittsburgh, Dept Surg, Pittsburgh, PA USA. [Kalinski, Pawel; Lotze, Michael T.; Whiteside, Theresa L.] Univ Pittsburgh, Inst Canc, Hillman Canc Ctr, Pittsburgh, PA USA. [Kalinski, Pawel] Univ Pittsburgh, Dept Immunol & Infect Dis & Microbiol, Pittsburgh, PA USA. [Kaerre, Klas; Klein, Eva] Karolinska Inst, Dept Microbiol Tumor & Cell Biol, Stockholm, Sweden. [Kepp, Oliver; Kroemer, Guido] Gustave Roussy Canc Campus, Metab & Cell Biol Platforms, Villejuif, France. [Kiessling, Rolf] Karolinska Inst Hosp, Dept Oncol, Stockholm, Sweden. [Kirkwood, John M.] Univ Pittsburgh, Canc Inst Lab, Pittsburgh, PA USA. [Knuth, Alexander] Hamad Med Corp, Natl Ctr Canc Care & Res, Doha, Qatar. [Lewis, Claire E.] Univ Sheffield, Sch Med, Dept Oncol, Acad Unit Inflammat & Tumour Targeting, Sheffield, S Yorkshire, England. [Liblau, Roland] Fac Med Toulouse, INSERM, UMR1043, F-31073 Toulouse, France. [Liblau, Roland] CNRS, UMR5282, Toulouse, France. [Liblau, Roland] Univ Toulouse 2, CHU Toulouse, Lab Immunol, Toulouse, France. [Lugli, Enrico; Mavilio, Domenico] Humanitas Clin & Res Inst, Unit Clin & Expt Immunol, Rozzano, Italy. [Mach, Jean-Pierre] Univ Lausanne, Dept Biochem, CH-1066 Epalinges, Switzerland. [Mavilio, Domenico] Univ Milan, Dept Med Biotechnol & Translat Med, Rozzano, Italy. [Melero, Ignacio] Univ Navarra, CIMA, Dept Immunol, E-31080 Pamplona, Spain. [Melero, Ignacio] Univ Navarra Clin, Dept Oncol, Pamplona, Spain. [Melief, Cornelis J.] ISA Therapeut, Leiden, Netherlands. [Melief, Cornelis J.] Leiden Univ, Med Ctr, Dept Immunohematol & Blood Transfus, Leiden, Netherlands. [Mittendorf, Elizabeth A.] Univ Texas Houston, MD Anderson Canc Ctr, Res Dept Surg Oncol, Houston, TX 77030 USA. [Moretta, Lorenzo] Ist Giannina Gaslini, I-16148 Genoa, Italy. [Odunsi, Adekunke] Roswell Pk Canc Inst, Ctr Immunotherapy, Buffalo, NY 14263 USA. [Okada, Hideho] Univ Calif San Francisco, Dept Neurol Surg, San Francisco, CA USA. [Palucka, Anna Karolina] Jackson Lab Genom Med, Farmington, CT USA. [Peter, Marcus E.] Northwestern Univ, Feinberg Sch Med, Div Hematol Oncol, Chicago, IL 60611 USA. [Pienta, Kenneth J.] Johns Hopkins Med Inst, James Buchanan Brady Urol Inst, Baltimore, MD 21205 USA. [Prendergast, George C.] Lankenau Inst Med Res, Wynnewood, PA USA. [Prendergast, George C.] Sidney Kimmel Med Coll, Dept Pathol Anat & Cell Biol, Philadelphia, PA USA. [Prendergast, George C.] Thomas Jefferson Univ, Kimmel Canc Ctr, Cell Biol & Signaling Program, Philadelphia, PA 19107 USA. [Rabinovich, Gabriel A.] IBYME, Lab Inmunopatol, Buenos Aires, DF, Argentina. [Restifo, Nicholas P.] NCI, NIH, Bethesda, MD 20892 USA. [Rizvi, Naiyer] Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. [Schreiber, Hans] Univ Chicago, Dept Pathol, Canc Res Ctr, Chicago, IL 60637 USA. [Seliger, Barbara] Univ Halle Wittenberg, Inst Med Immunol, D-06108 Halle, Germany. [Shiku, Hiroshi] Mie Univ, Grad Sch Med, Dept ImmunogeneTherapy, Tsu, Mie 514, Japan. [Silva-Santos, Bruno] Univ Lisbon, Inst Med Mol, P-1699 Lisbon, Portugal. [Smyth, Mark J.] QIMR Berghofer Med Res Inst, Immunol Canc & Infect Lab, Herston, Qld, Australia. [Smyth, Mark J.] Univ Queensland, Sch Med, Herston, Qld, Australia. [Speiser, Daniel E.] Univ Lausanne, Dept Oncol, Lausanne, Switzerland. [Speiser, Daniel E.] Ludwig Canc Res Ctr, Lausanne, Switzerland. [Srivastava, Pramod K.] Univ Connecticut, Sch Med, Dept Immunol, Farmington, CT USA. [Srivastava, Pramod K.] Carole & Ray Neag Comprehens Canc Ctr, Farmington, CT USA. [Talmadge, James E.] Univ Nebraska Med Ctr, Dept Pathol & Microbiol, Lab Transplantat Immunol, Omaha, NE USA. [Tartour, Eric] INSERM, U970, Paris, France. [Tartour, Eric] Paris Cardiovasc Res Ctr PARCC, Paris, France. [Tartour, Eric] HEGP, AP HP, Serv Immunol Biol, Paris, France. [Van der Burg, Sjoerd H.] Leiden Univ, Med Ctr, Dept Clin Oncol, Leiden, Netherlands. [Van den Eynde, Benoit J.] Ludwig Inst Canc Res, Brussels, Belgium. [Van den Eynde, Benoit J.] de Duve Inst, Brussels, Belgium. [Van den Eynde, Benoit J.] Catholic Univ Louvain, B-1200 Brussels, Belgium. [Vile, Richard] Mayo Clin, Coll Med, Dept Mol Med & Immunol, Rochester, MN USA. [Wagner, Hermann] Tech Univ Munich, Inst Med Microbiol Immunol & Hyg, D-80290 Munich, Germany. [Weber, Jeffrey S.] Univ S Florida, H Lee Moffitt Canc Ctr, Donald A Adam Comprehens Melanoma Res Ctr, Tampa, FL 33682 USA. [Whiteside, Theresa L.] Univ Pittsburgh, Sch Med, Pittsburgh, PA USA. [Wolchok, Jedd D.] MSKCC, Dept Med, New York, NY USA. [Wolchok, Jedd D.] MSKCC, Ludwig Ctr, New York, NY USA. [Wolchok, Jedd D.] Weill Cornell Med Coll, New York, NY USA. [Zitvogel, Laurence] INSERM, U1015, Villejuif, France. [Zitvogel, Laurence] Gustave Roussy Canc Campus, Ctr Invest Clin Biotherapie CICBT507 507, Villejuif, France. [Zou, Weiping] Univ Michigan, Sch Med, Ann Arbor, MI USA. [Kroemer, Guido] HEGP, AP HP, Pole Biol, Paris, France. RP Galluzzi, L (reprint author), Ctr Rech Cordeliers, Equipe Labellisee Pas Ligue Natl Canc 11, Paris, France. EM deadoc@vodafone.it RI Garg, Abhishek/D-5230-2012; Pienta, Kenneth/E-7679-2015; Bravo San Pedro, Jose Manuel/F-1680-2015; Caignard, Anne/F-8159-2013; Smyth, Mark/H-8709-2014; Mattei, Fabrizio/J-6585-2016; BRACCI, LAURA/J-8777-2016; Blay, Jean-Yves/N-3966-2016; Aranda, Fernando/N-2112-2014; Ayyoub, Maha/A-2074-2017; castelli, chiara/K-6899-2012; Giaccone, Giuseppe/E-8297-2017; OI Garg, Abhishek/0000-0002-9976-9922; Pienta, Kenneth/0000-0002-4138-2186; Smyth, Mark/0000-0001-7098-7240; Mattei, Fabrizio/0000-0002-5357-7773; BRACCI, LAURA/0000-0002-2535-4353; Blay, Jean-Yves/0000-0001-7190-120X; Aranda, Fernando/0000-0002-9364-474X; castelli, chiara/0000-0001-6891-8350; Giaccone, Giuseppe/0000-0002-5023-7562; Colombo, Mario Paolo/0000-0003-0042-7955; Restifo, Nicholas P./0000-0003-4229-4580; Mavilio, Domenico/0000-0001-6147-0952 FU Ligue contre le Cancer (equipe labelisee); Agence Nationale de la Recherche (ANR); Association pour la recherche sur le cancer (ARC); Canceropole Ile-de-France; Institut National du Cancer (INCa); Fondation Bettencourt-Schueller; Fondation de France; Fondation pour la Recherche Medicale (FRM); European Commission (ArtForce); European Research Council (ERC); LabEx Immuno-Oncology; SIRIC Stratified Oncology Cell DNA Repair and Tumor Immune Elimination (SOCRATE); SIRIC Cancer Research and Personalized Medicine (CARPEM); Paris Alliance of Cancer Research Institutes (PACRI); Association for Cancer Research (AIRC); Cancer Vaccine Collaborative and Cancer Research Institute; National Health and Medical Research Council of Australia; QIMR Berghofer Medical Research Institute; Susan G Komen Breast Cancer Foundation; Italian Ministry of Health FX GK is supported by the Ligue contre le Cancer (equipe labelisee); Agence Nationale de la Recherche (ANR); Association pour la recherche sur le cancer (ARC); Canceropole Ile-de-France; Institut National du Cancer (INCa); Fondation Bettencourt-Schueller; Fondation de France; Fondation pour la Recherche Medicale (FRM); the European Commission (ArtForce); the European Research Council (ERC); the LabEx Immuno-Oncology; the SIRIC Stratified Oncology Cell DNA Repair and Tumor Immune Elimination (SOCRATE); the SIRIC Cancer Research and Personalized Medicine (CARPEM); and the Paris Alliance of Cancer Research Institutes (PACRI). MPC is supported by Association for Cancer Research (AIRC). SG is supported by Cancer Vaccine Collaborative and Cancer Research Institute. MJS is supported by the National Health and Medical Research Council of Australia; the QIMR Berghofer Medical Research Institute; and the Susan G Komen Breast Cancer Foundation. FM is supported by a grant from the Italian Ministry of Health. NR 541 TC 87 Z9 91 U1 9 U2 101 PU IMPACT JOURNALS LLC PI ORCHARD PARK PA 6666 E QUAKER ST, STE 1, ORCHARD PARK, NY 14127 USA SN 1949-2553 J9 ONCOTARGET JI Oncotarget PD DEC 30 PY 2014 VL 5 IS 24 BP 12472 EP 12508 DI 10.18632/oncotarget.2998 PG 37 WC Oncology; Cell Biology SC Oncology; Cell Biology GA AZ2AX UT WOS:000348038000001 PM 25537519 ER PT J AU Chalfoun, J Majurski, M Dima, A Stuelten, C Peskin, A Brady, M AF Chalfoun, Joe Majurski, Michael Dima, Alden Stuelten, Christina Peskin, Adele Brady, Mary TI FogBank: a single cell segmentation across multiple cell lines and image modalities SO BMC BIOINFORMATICS LA English DT Article DE FogBank; Single cell segmentation; Robustness; Open-source ID WATERSHED TRANSFORM; ALGORITHMS; MICROSCOPY; CANCER; ROBUST AB Background: Many cell lines currently used in medical research, such as cancer cells or stem cells, grow in confluent sheets or colonies. The biology of individual cells provide valuable information, thus the separation of touching cells in these microscopy images is critical for counting, identification and measurement of individual cells. Over-segmentation of single cells continues to be a major problem for methods based on morphological watershed due to the high level of noise in microscopy cell images. There is a need for a new segmentation method that is robust over a wide variety of biological images and can accurately separate individual cells even in challenging datasets such as confluent sheets or colonies. Results: We present a new automated segmentation method called FogBank that accurately separates cells when confluent and touching each other. This technique is successfully applied to phase contrast, bright field, fluorescence microscopy and binary images. The method is based on morphological watershed principles with two new features to improve accuracy and minimize over-segmentation. First, FogBank uses histogram binning to quantize pixel intensities which minimizes the image noise that causes over-segmentation. Second, FogBank uses a geodesic distance mask derived from raw images to detect the shapes of individual cells, in contrast to the more linear cell edges that other watershed-like algorithms produce. We evaluated the segmentation accuracy against manually segmented datasets using two metrics. FogBank achieved segmentation accuracy on the order of 0.75 (1 being a perfect match). We compared our method with other available segmentation techniques in term of achieved performance over the reference data sets. FogBank outperformed all related algorithms. The accuracy has also been visually verified on data sets with 14 cell lines across 3 imaging modalities leading to 876 segmentation evaluation images. Conclusions: FogBank produces single cell segmentation from confluent cell sheets with high accuracy. It can be applied to microscopy images of multiple cell lines and a variety of imaging modalities. The code for the segmentation method is available as open-source and includes a Graphical User Interface for user friendly execution. C1 [Chalfoun, Joe; Majurski, Michael; Dima, Alden; Peskin, Adele; Brady, Mary] NIST, Informat Technol Lab, Gaithersburg, MD 20899 USA. [Stuelten, Christina] NCI, Cellular & Mol Biol Lab, NIH, Bethesda, MD 20892 USA. RP Chalfoun, J (reprint author), NIST, Informat Technol Lab, Gaithersburg, MD 20899 USA. EM joe.chalfoun@nist.gov NR 45 TC 6 Z9 6 U1 3 U2 11 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1471-2105 J9 BMC BIOINFORMATICS JI BMC Bioinformatics PD DEC 30 PY 2014 VL 15 AR 431 DI 10.1186/s12859-014-0431-x PG 12 WC Biochemical Research Methods; Biotechnology & Applied Microbiology; Mathematical & Computational Biology SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Mathematical & Computational Biology GA AZ8PG UT WOS:000348476800001 PM 25547324 ER PT J AU Pike, J Bogich, T Elwood, S Finnoff, DC Daszak, P AF Pike, Jamison Bogich, Tiffany Elwood, Sarah Finnoff, David C. Daszak, Peter TI Economic optimization of a global strategy to address the pandemic threat SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE emerging infectious diseases; One Health; adaptation; mitigation; climate change ID INTERNATIONAL HEALTH REGULATIONS; INFECTIOUS-DISEASES; AVIAN INFLUENZA; SURVEILLANCE; PREVENTION; EMERGENCE AB Emerging pandemics threaten global health and economies and are increasing in frequency. Globally coordinated strategies to combat pandemics, similar to current strategies that address climate change, are largely adaptive, in that they attempt to reduce the impact of a pathogen after it has emerged. However, like climate change, mitigation strategies have been developed that include programs to reduce the underlying drivers of pandemics, particularly animal-to-human disease transmission. Here, we use real options economic modeling of current globally coordinated adaptation strategies for pandemic prevention. We show that they would be optimally implemented within 27 y to reduce the annual rise of emerging infectious disease events by 50% at an estimated one-time cost of approximately $343.7 billion. We then analyze World Bank data on multilateral "One Health" pandemic mitigation programs. We find that, because most pandemics have animal origins, mitigation is a more cost-effective policy than business-asusual adaptation programs, saving between $344.0.7 billion and $360.3 billion over the next 100 y if implemented today. We conclude that globally coordinated pandemic prevention policies need to be enacted urgently to be optimally effective and that strategies to mitigate pandemics by reducing the impact of their underlying drivers are likely to be more effective than business as usual. C1 [Pike, Jamison; Finnoff, David C.] Univ Wyoming, Coll Business, Dept Econ & Finance, Laramie, WY 82071 USA. [Pike, Jamison; Bogich, Tiffany; Elwood, Sarah; Daszak, Peter] EcoHlth Alliance, New York, NY 10001 USA. [Bogich, Tiffany] NIH, Fogarty Int Ctr, Bethesda, MD 20892 USA. [Bogich, Tiffany] Princeton Univ, Dept Ecol Evolut Biol, Princeton, NJ 08544 USA. RP Daszak, P (reprint author), EcoHlth Alliance, New York, NY 10001 USA. EM daszak@ecohealthalliance.org OI Bogich, Tiffany/0000-0002-8143-5289 FU US Agency for International Development Emerging Pandemic Threats PREDICT; National Science Foundation (NSF)-NIH-US Department of Agriculture (USDA) Ecology and Evolution of Infectious Diseases program [DEB-1414374]; UK Biotechnology and Biological Sciences Research Council (BBSRC) [BB/M008894/1]; National Institute of General Medical Sciences at the National Institutes of Health [1R01-GM100471-01] FX This study was made possible by the generous support of the American people through the US Agency for International Development Emerging Pandemic Threats PREDICT, a US-UK collaborative award between the National Science Foundation (NSF)-NIH-US Department of Agriculture (USDA) Ecology and Evolution of Infectious Diseases program (Grant DEB-1414374) and the UK Biotechnology and Biological Sciences Research Council (BBSRC) (Grant BB/M008894/1), and by Grant 1R01-GM100471-01 from the National Institute of General Medical Sciences at the National Institutes of Health. NR 33 TC 9 Z9 9 U1 4 U2 31 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD DEC 30 PY 2014 VL 111 IS 52 BP 18519 EP 18523 DI 10.1073/pnas.1412661112 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA AY2UL UT WOS:000347444400039 PM 25512538 ER PT J AU Qiu, C McCann, KL Wine, RN Baserga, SJ Hall, TMT AF Qiu, Chen McCann, Kathleen L. Wine, Robert N. Baserga, Susan J. Hall, Traci M. Tanaka TI A divergent Pumilio repeat protein family for pre-rRNA processing and mRNA localization SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE Puf-A; crystal structure; Puf6; ribosome biogenesis; mRNA localization ID MINOR HISTOCOMPATIBILITY ANTIGEN; STEM-CELL TRANSPLANTATION; VERSUS-HOST-DISEASE; HOMOLOGY DOMAIN; PUF PROTEINS; BINDING; RECOGNITION; YEAST; SPECIFICITY; BIOGENESIS AB Pumilio/feminization of XX and XO animals (fem)-3 mRNA-binding factor (PUF) proteins bind sequence specifically to mRNA targets using a single-stranded RNA-binding domain comprising eight Pumilio (PUM) repeats. PUM repeats have now been identified in proteins that function in pre-rRNA processing, including human Puf-A and yeast Puf6. This is a role not previously ascribed to PUF proteins. Here we present crystal structures of human Puf-A that reveal a class of nucleic acid-binding proteins with 11 PUM repeats arranged in an "L"-like shape. In contrast to classical PUF proteins, Puf-A forms sequence-independent interactions with DNA or RNA, mediated by conserved basic residues. We demonstrate that equivalent basic residues in yeast Puf6 are important for RNA binding, pre-rRNA processing, and mRNA localization. Thus, PUM repeats can be assembled into alternative folds that bind to structured nucleic acids in addition to forming canonical eight-repeat crescent-shaped RNA-binding domains found in classical PUF proteins. C1 [Qiu, Chen; Wine, Robert N.; Hall, Traci M. Tanaka] NIEHS, Epigenet & Stem Cell Biol Lab, NIH, Res Triangle Pk, NC 27709 USA. [McCann, Kathleen L.; Baserga, Susan J.] Yale Univ, Sch Med, Dept Genet, New Haven, CT 06520 USA. [Baserga, Susan J.] Yale Univ, Sch Med, Dept Mol Biophys & Biochem, New Haven, CT 06520 USA. [Baserga, Susan J.] Yale Univ, Sch Med, Dept Therapeut Radiol, New Haven, CT 06520 USA. RP Baserga, SJ (reprint author), Yale Univ, Sch Med, Dept Genet, 333 Cedar St, New Haven, CT 06520 USA. EM susan.baserga@yale.edu; hall4@niehs.nih.gov OI McCann, Kathleen/0000-0002-7144-4851 FU National Institutes of Health, National Institute of Environmental Health Sciences and National Institutes of Health Grant [GM52581]; US Department of Energy, Office of Science, Office of Basic Energy Sciences [W-31-109-Eng-38]; Office of Science, Office of Basic Energy Sciences, of the US Department of Energy [DE-AC02-05CH11231] FX We thank L. Pedersen and the staff of the Southeast Regional Collaborative Access Team (SER-CAT) beamlines for assistance with X-ray data collection, J. Williams and the National Institute of Environmental Health Sciences (NIEHS) Protein Microcharacterization Facility for mass spectrometric analyses, J. Tucker and A. Janoshazi of the NIEHS Fluorescence Microscopy Imaging Center for imaging and data analysis support, G. Kissling for statistical analyses, and A. Clark for discussions regarding yeast growth and spheroplasting. This work was supported in part by the Intramural Research Program of the National Institutes of Health, National Institute of Environmental Health Sciences and National Institutes of Health Grant GM52581 (to S.J.B.). The Advanced Photon Source used for this study is supported by the US Department of Energy, Office of Science, Office of Basic Energy Sciences, under Contract W-31-109-Eng-38. The Advanced Light Source used for this study is supported by the Director, Office of Science, Office of Basic Energy Sciences, of the US Department of Energy under Contract DE-AC02-05CH11231. NR 34 TC 9 Z9 10 U1 0 U2 3 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD DEC 30 PY 2014 VL 111 IS 52 BP 18554 EP 18559 DI 10.1073/pnas.1407634112 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA AY2UL UT WOS:000347444400045 PM 25512524 ER PT J AU Wang, Q Oliveira, T Jankovic, M Silva, IT Hakim, O Yao, KH Gazumyan, A Mayer, CT Pavri, R Casellas, R Nussenzweig, MC Robbiani, DF AF Wang, Qiao Oliveira, Thiago Jankovic, Mila Silva, Israel T. Hakim, Ofir Yao, Kaihui Gazumyan, Anna Mayer, Christian T. Pavri, Rushad Casellas, Rafael Nussenzweig, Michel C. Robbiani, Davide F. TI Epigenetic targeting of activation-induced cytidine deaminase SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE chromosome translocation; mouse embryonic fibroblast; active enhancer; transcription elongation; lymphoma ID CLASS-SWITCH RECOMBINATION; SINGLE-STRANDED-DNA; SOMATIC HYPERMUTATION; CHROMOSOMAL TRANSLOCATIONS; ANTIBODY DIVERSIFICATION; TRANSCRIPTION INITIATION; NUCLEAR-ORGANIZATION; SEQUENCING REVEALS; CELL LYMPHOMAS; B-LYMPHOCYTES AB Activation-induced cytidine deaminase (AID) initiates class switch recombination (CSR) and somatic hypermutation (SHM) by deaminating cytosine residues in immunoglobulin genes (Igh, Ig kappa, and Ig lambda). At a lower frequency, AID also causes collateral DNA damage at non-Ig loci, including genes that are rearranged or mutated in Bcell lymphoma. Precisely how AID is recruited to these off-target sites is not entirely understood. To gain further insight into how AID selects its targets, we compared AID-mediated translocations in two different cell types, B cells and mouse embryonic fibroblasts (MEFs). AID targets a distinct set of hotspots in the two cell types. In both cases, hotspots are concentrated in highly transcribed but stalled genes. However, transcription alone is insufficient to recruit AID activity. Comparison of genes similarly transcribed in B cells and MEFs but targeted in only one of the two cell types reveals a common set of epigenetic features associated with AID recruitment in both cells. AID target genes are enriched in chromatin modifications associated with active enhancers (such as H3K27Ac) and marks of active transcription (such as H3K36me3) in both fibroblasts and B cells, indicating that these features are universal mediators of AID recruitment. C1 [Wang, Qiao; Oliveira, Thiago; Jankovic, Mila; Silva, Israel T.; Yao, Kaihui; Gazumyan, Anna; Mayer, Christian T.; Pavri, Rushad; Nussenzweig, Michel C.; Robbiani, Davide F.] Rockefeller Univ, Lab Mol Immunol, New York, NY 10065 USA. [Nussenzweig, Michel C.] Rockefeller Univ, Howard Hughes Med Inst, New York, NY 10065 USA. [Hakim, Ofir; Casellas, Rafael] NCI, NIAMSD, NIH, Bethesda, MD 20892 USA. RP Nussenzweig, MC (reprint author), Rockefeller Univ, Lab Mol Immunol, New York, NY 10065 USA. EM nussen@rockefeller.edu; drobbiani@rockefeller.edu RI Silva, Israel/N-3858-2014 OI Silva, Israel/0000-0002-4687-1499 FU European Molecular Biology Organization [ALTF 456-2014]; European Commission [GA-2012-600394]; NIH [AI037526] FX We thank members of the laboratory for discussions and suggestions, Dr. Feng Zhang (Harvard University) for providing Cas9 and sgRNA plasmids, David Bosque and Tom Eisenreich for help in managing the mouse colonies, and Klara Velinzon and Yelena Shatalina for FACS sorting. C. T. M. is supported by a European Molecular Biology Organization fellowship (ALTF 456-2014) and by the European Commission Seventh Framework Programme (Marie Curie Actions, EMBOCOFUND2012, GA-2012-600394). This work was supported in part by NIH Grant AI037526 (to M.C.N.). M.C.N. is a Howard Hughes Medical Institute Investigator. NR 36 TC 14 Z9 14 U1 0 U2 10 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD DEC 30 PY 2014 VL 111 IS 52 BP 18667 EP 18672 DI 10.1073/pnas.1420575111 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA AY2UL UT WOS:000347444400064 PM 25512519 ER PT J AU Chouikha, I Hinnebusch, BJ AF Chouikha, Iman Hinnebusch, B. Joseph TI Silencing urease: A key evolutionary step that facilitated the adaptation of Yersinia pestis to the flea-borne transmission route SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE Yersinia urease; plague; evolution; arthropod-borne transmission; pseudogene ID PLASMINOGEN-ACTIVATOR; PROTEOLYTIC ACTIVATION; PLAGUE; PSEUDOTUBERCULOSIS; VECTOR; GENE; BACILLUS; METALLOCENTER; BIOSYNTHESIS; VIRULENCE AB The arthropod-borne transmission route of Yersinia pestis, the bacterial agent of plague, is a recent evolutionary adaptation. Yersinia pseudotuberculosis, the closely related food-and water-borne enteric species from which Y. pestis diverged less than 6,400 y ago, exhibits significant oral toxicity to the flea vectors of plague, whereas Y. pestis does not. In this study, we identify the Yersinia urease enzyme as the responsible oral toxin. All Y. pestis strains, including those phylogenetically closest to the Y. pseudotuberculosis progenitor, contain a mutated ureD allele that eliminated urease activity. Restoration of a functional ureD was sufficient to make Y. pestis orally toxic to fleas. Conversely, deletion of the urease operon in Y. pseudotuberculosis rendered it nontoxic. Enzymatic activity was required for toxicity. Because urease-related mortality eliminates 30-40% of infective flea vectors, ureD mutation early in the evolution of Y. pestis was likely subject to strong positive selection because it significantly increased transmission potential. C1 [Chouikha, Iman; Hinnebusch, B. Joseph] NIAID, Lab Zoonot Pathogens, Rocky Mt Labs, NIH, Hamilton, MT 59840 USA. RP Chouikha, I (reprint author), NIAID, Lab Zoonot Pathogens, Rocky Mt Labs, NIH, Hamilton, MT 59840 USA. EM iman.chouikha@nih.gov FU Intramural Research Program of the NIAID, National Institutes of Health FX We thank Lisa Olano, Raynaldo Martin, and Carl Hammer [Protein Chemistry Section, Research Technologies Branch, National Institute of Allergy and Infectious Diseases (NIAID), National Institutes of Health] for mass spectrometry analysis and protein characterization. We thank Clayton Jarrett for his assistance with X. cheopis and O. montana fleas. We thank Christopher Bosio, James Carroll, Clayton Jarrett, Jeffrey Shannon, Justin Spinner, and Philip Stewart for critical review of the manuscript. This research was supported by the Intramural Research Program of the NIAID, National Institutes of Health. NR 45 TC 11 Z9 11 U1 5 U2 23 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD DEC 30 PY 2014 VL 111 IS 52 BP 18709 EP 18714 DI 10.1073/pnas.1413209111 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA AY2UL UT WOS:000347444400071 PM 25453069 ER PT J AU Yaffe, RB Kerr, MSD Damera, S Sarma, SV Inati, SK Zaghloul, KA AF Yaffe, Robert B. Kerr, Matthew S. D. Damera, Srikanth Sarma, Sridevi V. Inati, Sara K. Zaghloul, Kareem A. TI Reinstatement of distributed cortical oscillations occurs with precise spatiotemporal dynamics during successful memory retrieval SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE memory; intracranial EEG; oscillations; reinstatement ID MEDIAL TEMPORAL-LOBE; COMPLEMENTARY-LEARNING-SYSTEMS; MULTIVOXEL PATTERN-ANALYSIS; BRAIN OSCILLATIONS; HIPPOCAMPAL REPLAY; SUBSEQUENT MEMORY; NEURAL ACTIVITY; FREE-RECALL; CONTEXT; CONSOLIDATION AB Reinstatement of neural activity is hypothesized to underlie our ability to mentally travel back in time to recover the context of a previous experience. We used intracranial recordings to directly examine the precise spatiotemporal extent of neural reinstatement as 32 participants with electrodes placed for seizure monitoring performed a paired-associates episodic verbal memory task. By cueing recall, we were able to compare reinstatement during correct and incorrect trials, and found that successful retrieval occurs with reinstatement of a gradually changing neural signal present during encoding. We examined reinstatement in individual frequency bands and individual electrodes and found that neural reinstatement was largely mediated by temporal lobe theta and high-gamma frequencies. Leveraging the high temporal precision afforded by intracranial recordings, our data demonstrate that high-gamma activity associated with reinstatement preceded theta activity during encoding, but during retrieval this difference in timing between frequency bands was absent. Our results build upon previous studies to provide direct evidence that successful retrieval involves the reinstatement of a temporal context, and that such reinstatement occurs with precise spatiotemporal dynamics. C1 [Yaffe, Robert B.; Kerr, Matthew S. D.; Sarma, Sridevi V.] Johns Hopkins Univ, Dept Biomed Engn, Inst Computat Med, Baltimore, MD 21218 USA. [Damera, Srikanth; Zaghloul, Kareem A.] NINDS, Surg Neurol Branch, NIH, Bethesda, MD 20892 USA. [Inati, Sara K.] NINDS, Off Clin Director, NIH, Bethesda, MD 20892 USA. RP Zaghloul, KA (reprint author), NINDS, Surg Neurol Branch, NIH, Bethesda, MD 20892 USA. EM kareem.zaghloul@nih.gov FU National Institute of Neurological Disorders and Stroke; National Institutes of Health [MH055687, MH061975, NS067316, MH017168]; National Science Foundation (NSF) [1055560]; Burroughs Wellcome Fund Career Award at the Scientific Interface [1007274]; NSF Graduate Research Fellowship Program (GRFP) [DGE-1232825]; Achievement Rewards for College Scientists (ARCS) Foundation; Epilepsy Foundation Pre-doctoral Research Training Fellowship FX We thank Marc W. Howard, John F. Burke, John H. Wittig, Jr., and Michael J. Kahana for helpful and insightful comments on the manuscript. We thank the clinical teams at the University of Pennsylvania Hospital and Thomas Jefferson Hospital for assistance in data collection. We are indebted to all patients who have selflessly volunteered their time to participate in this study. This work was supported by the intramural research program of the National Institute of Neurological Disorders and Stroke. Data collection at the University of Pennsylvania and at Thomas Jefferson University was supported by National Institutes of Health Grants MH055687, MH061975, NS067316, and MH017168. S.V.S. was supported by the National Science Foundation (NSF) Career Award 1055560 and Burroughs Wellcome Fund Career Award at the Scientific Interface 1007274. M.S.D.K. was supported by NSF Graduate Research Fellowship Program (GRFP) DGE-1232825 and the Achievement Rewards for College Scientists (ARCS) Foundation. R.B.Y. was supported by the Epilepsy Foundation Pre-doctoral Research Training Fellowship. NR 34 TC 9 Z9 10 U1 5 U2 19 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD DEC 30 PY 2014 VL 111 IS 52 BP 18727 EP 18732 DI 10.1073/pnas.1417017112 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA AY2UL UT WOS:000347444400074 PM 25512550 ER PT J AU Wei, YH Reveal, B Reich, J Laursen, WJ Senger, S Akbar, T Iida-Jones, T Cai, WL Jarnik, M Lilly, MA AF Wei, Youheng Reveal, Brad Reich, John Laursen, Willem J. Senger, Stefania Akbar, Tanveer Iida-Jones, Takako Cai, Weili Jarnik, Michal Lilly, Mary A. TI TORC1 regulators Iml1/GATOR1 and GATOR2 control meiotic entry and oocyte development in Drosophila SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE meiosis; Iml1; GATOR1; GATOR2; Drosophila ID TUMOR-SUPPRESSOR COMPLEX; STEM-CELLS; SYNAPTONEMAL COMPLEX; NITROGEN STARVATION; WILD-TYPE; OOGENESIS; MELANOGASTER; RAPAMYCIN; PROTEIN; TARGET AB In single-cell eukaryotes the pathways that monitor nutrient availability are central to initiating the meiotic program and gametogenesis. In Saccharomyces cerevisiae an essential step in the transition to the meiotic cycle is the down-regulation of the nutrient-sensitive target of rapamycin complex 1 (TORC1) by the increased minichromosome loss 1/ GTPase-activating proteins toward Rags 1 (Iml1/GATOR1) complex in response to amino acid starvation. How metabolic inputs influence early meiotic progression and gametogenesis remains poorly understood in metazoans. Here we define opposing functions for the TORC1 regulatory complexes Iml1/GATOR1 and GATOR2 during Drosophila oogenesis. We demonstrate that, as is observed in yeast, the Iml1/GATOR1 complex inhibits TORC1 activity to slow cellular metabolism and drive the mitotic/meiotic transition in developing ovarian cysts. In iml1 germline depletions, ovarian cysts undergo an extra mitotic division before meiotic entry. The TORC1 inhibitor rapamycin can suppress this extra mitotic division. Thus, high TORC1 activity delays the mitotic/meiotic transition. Conversely, mutations in Tor, which encodes the catalytic subunit of the TORC1 complex, result in premature meiotic entry. Later in oogenesis, the GATOR2 components Mio and Seh1 are required to oppose Iml1/GATOR1 activity to prevent the constitutive inhibition of TORC1 and a block to oocyte growth and development. To our knowledge, these studies represent the first examination of the regulatory relationship between the Iml1/GATOR1 and GATOR2 complexes within the context of a multicellular organism. Our data imply that the central role of the Iml1/GATOR1 complex in the regulation of TORC1 activity in the early meiotic cycle has been conserved from single cell to multicellular organisms. C1 [Wei, Youheng; Reveal, Brad; Reich, John; Laursen, Willem J.; Senger, Stefania; Akbar, Tanveer; Iida-Jones, Takako; Cai, Weili; Jarnik, Michal; Lilly, Mary A.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Cell Biol & Metab Program, NIH, Bethesda, MD 20892 USA. RP Lilly, MA (reprint author), Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Cell Biol & Metab Program, NIH, Bethesda, MD 20892 USA. EM mlilly@helix.nih.gov OI Lilly, Mary/0000-0003-1564-619X FU National Institutes of Health (NIH)/National Institute of General Medical Sciences Grant [R01-GM084947]; NIH [P40OD018537]; Intramural Program of the Eunice Kennedy Shriver National Institute of Child Health and Human Development, NIH [ZIA HD001613 16] FX We thank Aurello Teleman, Thomas Neufeld, Eric Baehrecke, and Helmut Kramer for providing reagents and the Transgenic RNAi Project at Harvard Medical School [supported by National Institutes of Health (NIH)/National Institute of General Medical Sciences Grant R01-GM084947] for providing transgenic RNAi plasmid vectors used in this study. Some stocks used in this study were obtained from the Bloomington Drosophila Stock Center (supported by NIH Grant P40OD018537). This work was supported by Grant ZIA HD001613 16 from the Intramural Program of the Eunice Kennedy Shriver National Institute of Child Health and Human Development, NIH. NR 43 TC 5 Z9 5 U1 0 U2 8 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD DEC 30 PY 2014 VL 111 IS 52 BP E5670 EP E5677 DI 10.1073/pnas.1419156112 PG 8 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA AY2UL UT WOS:000347444400012 PM 25512509 ER PT J AU Balasubramanian, R Robaye, B Boeynaems, JM Jacobson, KA AF Balasubramanian, Ramachandran Robaye, Bernard Boeynaems, Jean-Marie Jacobson, Kenneth A. TI Enhancement of Glucose Uptake in Mouse Skeletal Muscle Cells and Adipocytes by P2Y(6) Receptor Agonists SO PLOS ONE LA English DT Article ID ACTIVATED PROTEIN-KINASE; G(Q)-COUPLED RECEPTOR; DEPENDENT MECHANISM; INSULIN-SECRETION; GLUT4 PROMOTER; IN-VIVO; TRANSCRIPTION; TRANSPORT; MICE; UDP AB Glucose uptake by peripheral tissues such as skeletal muscles and adipocytes is important in the maintenance of glucose homeostasis. We previously demonstrated that P2Y(6) receptor (P2Y(6)R) agonists protect pancreatic islet cells from apoptosis and stimulate glucose-dependent insulin release. Here, we investigated the effects of P2Y(6)R activation on glucose uptake in insulin target tissues. An agonist of the P2Y(6)R, P-1-(5'-uridine)-P-3-(5'-N-4-methoxycytidine)-triphosphate (MRS2957), significantly increased the uptake of [H-3]2-deoxyglucose in mouse C2C12 myotubes and 3T3-L1 adipocytes, and this stimulation was significantly decreased by a selective P2Y6R antagonist N,N'-1,4-butanediyl-bis[N'-(3-isothiocyanatophenyl)thiourea] (MRS2578). Pre-incubation with Compound C (an inhibitor of 5'-AMP-activated protein kinase, AMPK), or AMPK siRNA abolished the stimulatory effect of MRS2957 on glucose uptake. Also, MRS2957 (60 min incubation) increased recruitment of the facilitated glucose transporter-4 (GLUT4) to the cell membrane, which was blocked by MRS2578. Treatment of C2C12 myotubes with MRS2957 induced significant phosphorylation of AMPK, which increase GLUT4 expression through histone deacetylase (HDAC) 5 signaling. Glucose uptake in primary mouse adipocytes from wild-type mice was stimulated upon P2Y6R activation by either MRS2957 or native agonist UDP, and the P2Y(6)R effect was antagonized by MRS2578. However, in adipocytes from P2Y(6)R-knockout mice P2Y(6)R agonists had no effect on glucose uptake, and there was no change in the glucose uptake by insulin. Our results indicate that the P2Y(6)R promotes glucose metabolism in peripheral tissues, which may be mediated through AMPK signaling. C1 [Balasubramanian, Ramachandran; Jacobson, Kenneth A.] NIDDK, Mol Recognit Sect, Bioorgan Chem Lab, NIH, Bethesda, MD 20892 USA. [Robaye, Bernard] Univ Libre Bruxelles, IRIBHM, Inst Interdisciplinary Res, Gosselies, Belgium. [Boeynaems, Jean-Marie] Univ Libre Bruxelles, Brussels, Belgium. 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 OI Jacobson, Kenneth/0000-0001-8104-1493 FU Intramural Research Program of NIDDK, National Institutes of Health, Bethesda, MD, USA [Z01 DK031116-27] FX This work was supported by Intramural Research Program of NIDDK, National Institutes of Health, Bethesda, MD, USA; Grant: Z01 DK031116-27. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 42 TC 6 Z9 6 U1 0 U2 8 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 30 PY 2014 VL 9 IS 12 AR e116203 DI 10.1371/journal.pone.0116203 PG 19 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA AX6YH UT WOS:000347063500060 PM 25549240 ER PT J AU Henderson, SE Vallejo, AI Ely, BA Kang, GX Roy, AK Pine, DS Stern, ER Gabbay, V AF Henderson, Sarah E. Vallejo, Ana I. Ely, Benjamin A. Kang, Guoxin Roy, Amy Krain Pine, Daniel S. Stern, Emily R. Gabbay, Vilma TI The neural correlates of emotional face-processing in adolescent depression: a dimensional approach focusing on anhedonia and illness severity SO PSYCHIATRY RESEARCH-NEUROIMAGING LA English DT Article DE Adolescents; Depression; Anhedonia; Emotion perception; fMRI; Faces ID HAPPY FACIAL EXPRESSIONS; MAJOR DEPRESSION; ANTIDEPRESSANT TREATMENT; BRAIN ACTIVATION; DISORDER; FMRI; CHILDREN; RESPONSES; METAANALYSIS; PREDICTORS AB Deficits in emotion processing, a known clinical feature of major depressive disorder (MDD), have been widely investigated using emotional face paradigms and neuroimaging. However, most studies have not accounted for the high inter-subject variability of symptom severity. Similarly, only sparse research has focused on MDD in adolescence, early in the course of the illness. Here we sought to investigate neural responses to emotional faces using both categorical and dimensional analyses with a focus on anhedonia, a core symptom of MDD associated with poor outcomes. Nineteen medication-free depressed adolescents and 18 healthy controls (HC) were scanned during presentation of happy, sad, fearful, and neutral faces. ANCOVAs and regressions assessed group differences and relationships with illness and anhedonia severity, respectively. Findings included a group by valence interaction with depressed adolescents exhibiting decreased activity in the superior temporal gyrus (STG), putamen and premotor cortex. Post-hoc analyses confirmed decreased STG activity in MDD adolescents. Dimensional analyses revealed associations between illness severity and altered responses to negative faces in prefrontal, cingulate, striatal, and limbic regions. However, anhedonia severity was uniquely correlated with responses to happy faces in the prefrontal, cingulate, and insular regions. Our work highlights the need for studying specific symptoms dimensionally in psychiatric research. (C) 2014 Elsevier Ireland Ltd. All rights reserved. C1 [Henderson, Sarah E.; Vallejo, Ana I.; Stern, Emily R.; Gabbay, Vilma] Icahn Sch Med Mt Sinai, Dept Psychiat, New York, NY 10029 USA. [Ely, Benjamin A.; Stern, Emily R.; Gabbay, Vilma] Icahn Sch Med Mt Sinai, Dept Neurosci, New York, NY 10029 USA. [Kang, Guoxin] Weill Cornell Med Coll, Dept Radiol, New York, NY USA. [Roy, Amy Krain] Fordham Univ, Dept Psychol, New York, NY 10023 USA. [Pine, Daniel S.] NIMH, Bethesda, MD 20892 USA. [Gabbay, Vilma] Nathan S Kline Inst Psychiat Res, Orangeburg, NY 10962 USA. RP Gabbay, V (reprint author), Icahn Sch Med Mt Sinai, Dept Psychiat, 1230 Gustave L Levy Pl, New York, NY 10029 USA. EM vilma.gabbay@mssm.edu FU National Institutes of Health [AT004576, AT002395, MH095807]; Chrissy Rossi National Alliance for Research on Schizophrenia and Depression [16328]; Hope for Depression Research Foundation (RGA) [9-012] FX This study was supported by grants from the National Institutes of Health (AT004576, AT002395, MH095807), the Chrissy Rossi National Alliance for Research on Schizophrenia and Depression (16328), the Hope for Depression Research Foundation (RGA#9-012), and generous gifts from the Leon Levy Foundation. NR 52 TC 10 Z9 11 U1 4 U2 25 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0925-4927 EI 1872-7506 J9 PSYCHIAT RES-NEUROIM JI Psychiatry Res. Neuroimaging PD DEC 30 PY 2014 VL 224 IS 3 BP 234 EP 241 DI 10.1016/j.pscychresns.2014.09.006 PG 8 WC Clinical Neurology; Neuroimaging; Psychiatry SC Neurosciences & Neurology; Psychiatry GA AU3QG UT WOS:000345527900012 PM 25448398 ER PT J AU Tong, SQ Ito, Y Ma, Y AF Tong, Shengqiang Ito, Yoichiro Ma, Ying TI Enantioseparation of DL-tryptophan by spiral tube assembly counter-current chromatography and evaluation of mass transfer rate for enantiomers SO JOURNAL OF CHROMATOGRAPHY A LA English DT Article; Proceedings Paper CT 8th International Conference on Countercurrent Chromatography (CCC) CY JUL 23-25, 2014 CL Uxbridge, ENGLAND DE Counter-current chromatography; Enantioseparation; DL-Tryptophan; Aqueous-aqueous solvent system; Bovine serum albumin; Mass transfer rate ID BOVINE-SERUM-ALBUMIN; PROTEIN STATIONARY PHASES; AQUEOUS 2-PHASE SYSTEM; AFFINITY-CHROMATOGRAPHY; OPTICAL RESOLUTION; SOLVENT SYSTEMS; SEPARATION; BEHAVIOR; AGAROSE; BINDING AB Spiral tube assembly counter-current chromatography was successfully applied in enantioseparation of DL-tryptophan using bovine serum albumin as chiral selector. An improved biphasic aqueous-aqueous solvent system 12.0% (w/w) polyethyleneglycol 8000-9.0% (w/w) dibasic potassium phosphate-0.1% ammonia-78.9% water was used as the solvent system for counter-current chromatography, in which bovine serum albumin was predominantly distributed in the lower phase of the two-phase aqueous system. The aqueous-aqueous solvent system gave a very high enantioselectivity for D- and L-tryptophan at alpha = 2.605 along with distribution ratio D-D = 1.200 and D-L = 0.461. High peak resolution was obtained for enantioseparation of 2.0 mg of DL-tryptophan by spiral tube assembly counter-current chromatography under room temperature. It was found that 0.1% ammonia added in the aqueous-aqueous solvent system greatly improved the enantioseparations. An unusual extremely broad peak for L-tryptophan was observed during enantioseparations. In order to give an explanation, mass transfer rates of D- and L-enantiomers through the interface between the two phases were measured. It was found that L-tryptophan showed lower mass transfer rate than D-tryptophan. Further discussions were proposed for possible reasons for mass transfer rate difference between the enantiomers. Published by Elsevier B.V. C1 [Tong, Shengqiang] Zhejiang Univ Technol, Coll Pharmaceut Sci, Hangzhou 310032, Zhejiang, Peoples R China. [Tong, Shengqiang; Ito, Yoichiro] NHLBI, Lab Bioseparat Technol, Biochem & Biophys Ctr, NIH, Bethesda, MD 20892 USA. [Ma, Ying] Natl Inst Biomed Imaging & Bioengn, Lab Mol Imaging & Nanomed, 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 FU Natural Science Foundation of P. R. China [21105090]; Department of Education of Zhejiang Province of China [pd2013031] FX This work was partially supported by Natural Science Foundation of P. R. China (21105090), Department of Education of Zhejiang Province of China (pd2013031). S.Q, Tong also thanks Personnel Department of Zhejiang University of Technology for providing the visiting scholar program (Zhaohui Program 2011). NR 25 TC 6 Z9 7 U1 3 U2 13 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0021-9673 EI 1873-3778 J9 J CHROMATOGR A JI J. Chromatogr. A PD DEC 29 PY 2014 VL 1374 BP 77 EP 84 DI 10.1016/j.chroma.2014.11.013 PG 8 WC Biochemical Research Methods; Chemistry, Analytical SC Biochemistry & Molecular Biology; Chemistry GA AY5ID UT WOS:000347605000009 PM 25476690 ER PT J AU Bihlmeyer, NA Brody, JA Smith, AV Lunetta, KL Nalls, M Smith, JA Tanaka, T Davies, G Yu, L Mirza, SS Teumer, A Coresh, J Pankow, JS Franceschini, N Scaria, A Oshima, J Psaty, BM Gudnason, V Eiriksdottir, G Harris, TB Li, HY Karasik, D Kiel, DP Garcia, M Liu, YM Faul, JD Kardia, SLR Zhao, W Ferrucci, L Allerhand, M Liewald, DC Redmond, P Starr, JM De Jager, PL Evans, DA Direk, N Ikram, MA Uitterlinden, A Homuth, G Lorbeer, R Grabe, HJ Launer, L Murabito, JM Singleton, AB Weir, DR Bandinelli, S Deary, IJ Bennett, DA Tiemeier, H Kocher, T Lumley, T Arking, DE AF Bihlmeyer, Nathan A. Brody, Jennifer A. Smith, Albert Vernon Lunetta, Kathryn L. Nalls, Mike Smith, Jennifer A. Tanaka, Toshiko Davies, Gail Yu, Lei Mirza, Saira Saeed Teumer, Alexander Coresh, Josef Pankow, James S. Franceschini, Nora Scaria, Anish Oshima, Junko Psaty, Bruce M. Gudnason, Vilmundur Eiriksdottir, Gudny Harris, Tamara B. Li, Hanyue Karasik, David Kiel, Douglas P. Garcia, Melissa Liu, Yongmei Faul, Jessica D. Kardia, Sharon L. R. Zhao, Wei Ferrucci, Luigi Allerhand, Michael Liewald, David C. Redmond, Paul Starr, John M. De Jager, Philip L. Evans, Denis A. Direk, Nese Ikram, Mohammed Arfan Uitterlinden, Andre Homuth, Georg Lorbeer, Roberto Grabe, Hans J. Launer, Lenore Murabito, Joanne M. Singleton, Andrew B. Weir, David R. Bandinelli, Stefania Deary, Ian J. Bennett, David A. Tiemeier, Henning Kocher, Thomas Lumley, Thomas Arking, Dan E. TI Genetic diversity is a predictor of mortality in humans SO BMC GENETICS LA English DT Article DE Heterozygosity; Human; Survival; GWAS ID FACIAL ATTRACTIVENESS; HETEROZYGOSITY; DISEASES; TRAITS; HEALTH AB Background: It has been well-established, both by population genetics theory and direct observation in many organisms, that increased genetic diversity provides a survival advantage. However, given the limitations of both sample size and genome-wide metrics, this hypothesis has not been comprehensively tested in human populations. Moreover, the presence of numerous segregating small effect alleles that influence traits that directly impact health directly raises the question as to whether global measures of genomic variation are themselves associated with human health and disease. Results: We performed a meta-analysis of 17 cohorts followed prospectively, with a combined sample size of 46,716 individuals, including a total of 15,234 deaths. We find a significant association between increased heterozygosity and survival (P = 0.03). We estimate that within a single population, every standard deviation of heterozygosity an individual has over the mean decreases that person's risk of death by 1.57%. Conclusions: This effect was consistent between European and African ancestry cohorts, men and women, and major causes of death (cancer and cardiovascular disease), demonstrating the broad positive impact of genomic diversity on human survival. C1 [Bihlmeyer, Nathan A.] Johns Hopkins Univ, Sch Med, Predoctoral Training Program Human Genet, McKusick Nathans Inst Genet Med, Baltimore, MD USA. [Bihlmeyer, Nathan A.; Arking, Dan E.] Johns Hopkins Univ, Sch Med, McKusick Nathans Inst Genet Med, Baltimore, MD 21205 USA. [Scaria, Anish; Lumley, Thomas] Univ Auckland, Dept Stat, Sci Ctr 303 325, Auckland 1142, New Zealand. [Oshima, Junko] Univ Washington, Dept Pathol, Seattle, WA 98195 USA. [Psaty, Bruce M.] Univ Washington, Dept Med, Seattle, WA USA. [Psaty, Bruce M.] Univ Washington, Dept Epidemiol, Seattle, WA 98195 USA. [Psaty, Bruce M.] Univ Washington, Dept Hlth Serv, Seattle, WA 98195 USA. [Nalls, Mike; Singleton, Andrew B.] NIA, Lab Neurogenet, NIH, Bethesda, MD 20892 USA. [Garcia, Melissa] NIA, Lab Epidemiol Demog & Biometry, NIH, Bethesda, MD 20892 USA. [Liu, Yongmei] Wake Forest Univ, Bowman Gray Sch Med, Dept Epidemiol & Prevent, Div Publ Hlth Sci, Winston Salem, NC USA. [Lunetta, Kathryn L.; Li, Hanyue] Boston Univ, Sch Publ Hlth, Dept Biostat, Boston, MA USA. [Lunetta, Kathryn L.; Murabito, Joanne M.] NHLBI, Framingham Heart Study, Framingham, MA USA. [Murabito, Joanne M.] Boston Univ, Sch Med, Dept Med, Sect Gen Internal Med, Boston, MA 02118 USA. [Karasik, David; Kiel, Douglas P.] Beth Israel Deaconess Med Ctr, Dept Med, Inst Aging Res, Cambridge, MA USA. [Karasik, David; Kiel, Douglas P.] Harvard Univ, Sch Med, Cambridge, MA 02138 USA. [Faul, Jessica D.; Weir, David R.] Univ Michigan, Inst Social Res, Survey Res Ctr, Ann Arbor, MI USA. [Smith, Jennifer A.; Kardia, Sharon L. R.; Zhao, Wei] Univ Michigan, Sch Publ Hlth, Dept Epidemiol, Ann Arbor, MI 48109 USA. [Davies, Gail; Allerhand, Michael; Liewald, David C.; Starr, John M.; Deary, Ian J.] Univ Edinburgh, Ctr Cognit Ageing & Cognit Epidemiol, Edinburgh, Midlothian, Scotland. [Davies, Gail; Redmond, Paul; Deary, Ian J.] Univ Edinburgh, Dept Psychol, Edinburgh, Midlothian, Scotland. [Starr, John M.] Univ Edinburgh, Alzheimer Scotland Dementia Res Ctr, Edinburgh, Midlothian, Scotland. [Yu, Lei; Bennett, David A.] Rush Univ, Rush Alzheimers Dis Ctr, Med Ctr, Chicago, IL 60612 USA. [De Jager, Philip L.] Brigham & Womens Hosp, Dept Neurol, Program Translat NeuroPsychiat Genom, Boston, MA 02115 USA. [De Jager, Philip L.] Harvard Univ, Sch Med, Boston, MA USA. [Evans, Denis A.] Rush Univ, Rush Inst Hlth Aging, Med Ctr, Chicago, IL 60612 USA. [Evans, Denis A.] Rush Univ, Dept Internal Med, Med Ctr, Chicago, IL 60612 USA. [Mirza, Saira Saeed; Direk, Nese; Ikram, Mohammed Arfan; Uitterlinden, Andre; Tiemeier, Henning] Erasmus MC, Dept Epidemiol, Rotterdam, Netherlands. [Ikram, Mohammed Arfan] Erasmus MC, Dept Neurol, Rotterdam, Netherlands. [Ikram, Mohammed Arfan] Erasmus MC, Dept Radiol, Rotterdam, Netherlands. [Tiemeier, Henning] Erasmus MC, Dept Child & Adolescent Psychiat, Rotterdam, Netherlands. [Tiemeier, Henning] Erasmus MC, Dept Psychiat, Rotterdam, Netherlands. [Uitterlinden, Andre] Erasmus MC, Dept Internal Med, Rotterdam, Netherlands. [Teumer, Alexander; Homuth, Georg] Univ Med Greifswald, Interfac Inst Genet & Funct Genom, Greifswald, Germany. [Teumer, Alexander; Lorbeer, Roberto] Univ Med Greifswald, Inst Community Med, Greifswald, Germany. [Grabe, Hans J.] Univ Med Greifswald, HELIOS Hosp Stralsund, Dept Psychiat & Psychotherapy, Greifswald, Germany. [Grabe, Hans J.] German Ctr Neurodegenerat Dis DZNE, Greifswald, Germany. [Kocher, Thomas] Univ Med Greifswald, Dept Restorat Dent Periodontol & Endodontol, Unit Periodontol, Greifswald, Germany. [Smith, Albert Vernon; Gudnason, Vilmundur; Eiriksdottir, Gudny] Iceland Heart Assoc, Kopavogur, Iceland. [Smith, Albert Vernon; Gudnason, Vilmundur] Univ Iceland, Reykjavik, Iceland. [Harris, Tamara B.; Launer, Lenore] NIA, NIH, Bethesda, MD 20892 USA. [Brody, Jennifer A.] Univ Washington, Dept Med, Cardiovasc Hlth Res Unit, Seattle, WA USA. [Tanaka, Toshiko; Ferrucci, Luigi] NIA, Translat Gerontol Branch, Baltimore, MD 21224 USA. [Bandinelli, Stefania] ASF, Geriatr Unit, Florence, Italy. [Coresh, Josef] Johns Hopkins Bloomberg Sch Publ Hlth, Dept Epidemiol, Baltimore, MD USA. [Pankow, James S.] Univ Minnesota, Div Epidemiol & Community Hlth, Minneapolis, MN USA. [Franceschini, Nora] Univ N Carolina, Sch Publ Hlth, Dept Epidemiol, Chapel Hill, NC 27514 USA. RP Lumley, T (reprint author), Univ Auckland, Dept Stat, Sci Ctr 303 325, Private Bag 92019, Auckland 1142, New Zealand. EM t.lumley@auckland.ac.nz; arking@jhmi.edu RI Singleton, Andrew/C-3010-2009; Gudnason, Vilmundur/K-6885-2015; Smith, Albert/K-5150-2015; OI Gudnason, Vilmundur/0000-0001-5696-0084; Smith, Albert/0000-0003-1942-5845; Tiemeier, Henning/0000-0002-4395-1397; Bihlmeyer, Nathan/0000-0002-4415-7419; Karasik, David/0000-0002-8826-0530; Pankow, James/0000-0001-7076-483X FU NIGMS [5T32GM07814]; National Science Foundation [DGE-1232825]; National Heart, Lung, and Blood Institute [HHSN268201100005C, HHSN268201100006C, HHSN268201100007C, HHSN268201100008C, HHSN268201100009C, HHSN268201100010C, HHSN268201100011C, HHSN268201100012C, R01HL087641, R01HL59367, R01HL086694]; National Human Genome Research Institute [U01HG004402]; National Institutes of Health [HHSN268200625226C, UL1RR025005, HHSN268200782096C]; NIH Roadmap for Medical Research; NIH [N01-AG-12100, Z01 AG000949-02, Z01 AG007390-07]; NIA Intramural Research Program, Hjartavernd (the Icelandic Heart Association); Althingi (the Icelandic Parliament); NHLBI [HHSN268201200036C, HHSN268200800007C, N01HC55222, N01HC85079, N01HC85080, N01HC85081, N01HC85082, N01HC85083, N01HC85086, HL080295, HL087652, HL105756, HL085251]; National Institute on Aging (NIA) [AG023629]; National Center for Advancing Translational Sciences, CTSI [UL1TR000124]; National Institute of Diabetes and Digestive and Kidney Disease Diabetes Research Center (DRC) [DK063491]; National Institute of Aging [Z01 AG000949-02, Z01 AG007390-07, R01AG29451, NIA U01AG009740, RC2 AG036495, RC4 AG039029, P30AG10161, R01AG17917, R01AG15819, R01AG30146]; National Heart, Lung and Blood Institute's Framingham Heart Study [N01-HC-25195]; Affymetrix, Inc [N02-HL-6-4278]; Robert Dawson Evans Endowment of the Department of Medicine at Boston University School of Medicine; Boston Medical Center; National Institute of Arthritis Musculoskeletal and Skin Diseases [R01 AR41398]; NIA [N01AG62101, N01AG62103, N01AG62106, 1R01AG03209801A1]; Italian Ministry of Health [ICS110.1/RF97.71]; U.S. National Institute on Aging [263 MD 9164, 263 MD 821336]; BBSRC; Royal Society; Chief Scientist Office of the Scottish Government; Age UK (The Disconnected Mind project); UK Biotechnology and Biological Sciences Research Council (BBSRC); Medical Research Council (MRC); Illinois Department of Public Health; Translational Genomics Research Institute; Erasmus Medical Centre; Erasmus University Rotterdam; Netherlands Organization for Scientific Research (NWO); Netherlands Organization for Health Research and Development (ZonMw); Research Institute for Diseases in the Elderly (RIDE); Netherlands Genomics Initiative; Ministry of Education, Culture and Science; Ministry of Health, Welfare and Sports; European Commission (DG XII); Municipality of Rotterdam; ZonMw [2009-017.106.370]; NWO; Federal Ministry of Education and Research [01ZZ9603, 01ZZ0103, 01ZZ0403, 03ZIK012]; Ministry of Cultural Affairs; Social Ministry of the Federal State of Mecklenburg-West Pomerania; network 'Greifswald Approach to Individualized Medicine (GANI_MED)' - Federal Ministry of Education and Research [03IS2061A]; Siemens Healthcare, Erlangen, Germany; Federal State of Mecklenburg-West Pomerania FX Funded in part by training grant (NIGMS) 5T32GM07814. This material is based upon work supported by the National Science Foundation Graduate Research Fellowship under Grant No. DGE-1232825. Any opinion, findings, and conclusions or recommendations expressed in this material are those of the authors(s) and do not necessarily reflect the views of the National Science Foundation.; Cohorts; ARIC; The Atherosclerosis Risk in Communities Study is carried out as a collaborative study supported by National Heart, Lung, and Blood Institute contracts (HHSN268201100005C, HHSN268201100006C, HHSN268201100007C, HHSN268201100008C, HHSN268201100009C, HHSN268201100010C, HHSN268201100011C, and HHSN268201100012C), R01HL087641, R01HL59367 and R01HL086694; National Human Genome Research Institute contract U01HG004402; and National Institutes of Health contract HHSN268200625226C. The authors thank the staff and participants of the ARIC study for their important contributions. Infrastructure was partly supported by Grant Number UL1RR025005, a component of the National Institutes of Health and NIH Roadmap for Medical Research.; AGES; The Age, Gene/Environment Susceptibility Reykjavik Study has been funded by NIH contract N01-AG-12100, the NIA Intramural Research Program, Hjartavernd (the Icelandic Heart Association), and the Althingi (the Icelandic Parliament). The study is approved by the Icelandic National Bioethics Committee, (VSN: 00-063) and the Data Protection Authority. The researchers are indebted to the participants for their willingness to participate in the study.; CHS; Cardiovascular Health Study: This CHS research was supported by NHLBI contracts HHSN268201200036C, HHSN268200800007C, N01HC55222, N01HC85079, N01HC85080, N01HC85081, N01HC85082, N01HC85083, N01HC85086; and NHLBI grants HL080295, HL087652, HL105756, HL085251 with additional contribution from the National Institute of Neurological Disorders and Stroke (NINDS). Additional support was provided through AG023629 from the National Institute on Aging (NIA). A full list of principal CHS investigators and institutions can be found at CHS-NHLBI.org/.; The provision of genotyping data was supported in part by the National Center for Advancing Translational Sciences, CTSI grant UL1TR000124, and the National Institute of Diabetes and Digestive and Kidney Disease Diabetes Research Center (DRC) grant DK063491 to the Southern California Diabetes Endocrinology Research Center.; The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.; FHS; Funding: The Framingham Heart Study analyses were supported by the National Institute of Aging (R01AG29451). This research was conducted in part using data and resources from the Framingham Heart Study of the National Heart Lung and Blood Institute of the National Institutes of Health and Boston University School of Medicine. The analyses reflect intellectual input and resource development from the Framingham Heart Study investigators participating in the SNP Health Association Resource (SHARe) project. This work was partially supported by the National Heart, Lung and Blood Institute's Framingham Heart Study (Contract No. N01-HC-25195) and its contract with Affymetrix, Inc for genotyping services (Contract No. N02-HL-6-4278). A portion of this research utilized the Linux Cluster for Genetic Analysis (LinGA-II) funded by the Robert Dawson Evans Endowment of the Department of Medicine at Boston University School of Medicine and Boston Medical Center. Dr. Kiel was partially supported by the National Institute of Arthritis Musculoskeletal and Skin Diseases (R01 AR41398).; HealthABC; This research was supported by NIA contracts N01AG62101, N01AG62103, and N01AG62106 and was supported in part by the Intramural Research Program of the NIH, National Institute on Aging (Z01 AG000949-02 and Z01 AG007390-07, Human subjects protocol UCSF IRB is H5254-12688-11). The genome-wide association study was funded by NIA grant 1R01AG03209801A1 to Wake Forest University Health Sciences and genotyping services were provided by the Center for Inherited Disease Research (CIDR). CIDR is fully funded through a federal contract from the National Institutes of Health to The Johns Hopkins University, contract number HHSN268200782096C. 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).; HRS; HRS is supported by the National Institute on Aging (NIA U01AG009740). The genotyping was funded separately by the National Institute on Aging (RC2 AG036495, RC4 AG039029). Our genotyping was conducted by the NIH Center for Inherited Disease Research (CIDR) at Johns Hopkins University. Genotyping quality control and final preparation of the data were performed by the Genetics Coordinating Center at the University of Washington.; InCHIANTI; The InCHIANTI study baseline (1998-2000) was supported as a "targeted project" (ICS110.1/RF97.71) by the Italian Ministry of Health and in part by the U.S. National Institute on Aging (Contracts: 263 MD 9164 and 263 MD 821336).; LBC; Lothian Birth Cohorts 1921 and 1936 (LBC1921, LBC1936); We thank the cohort participants and team members who contributed to these studies. Phenotype collection in the Lothian Birth Cohort 1921 was supported by the BBSRC, The Royal Society and The Chief Scientist Office of the Scottish Government. Phenotype collection in the Lothian Birth Cohort 1936 was supported by Age UK (The Disconnected Mind project).; Genotyping of the cohorts was funded by the UK Biotechnology and Biological Sciences Research Council (BBSRC). The work was undertaken by The University of Edinburgh Centre for Cognitive Ageing and Cognitive Epidemiology, part of the cross council Lifelong Health and Wellbeing Initiative (MR/K026992/1). Funding from the BBSRC, and Medical Research Council (MRC) is gratefully acknowledged.; MAP/ROS; The MAP and ROS data used in this analysis was supported by National Institute on Aging grants P30AG10161, R01AG17917, R01AG15819, R01AG30146, the Illinois Department of Public Health, and the Translational Genomics Research Institute.; Rotterdam; The Rotterdam Study is supported by Erasmus Medical Centre and Erasmus University Rotterdam, the Netherlands Organization for Scientific Research (NWO), the Netherlands Organization for Health Research and Development (ZonMw), the Research Institute for Diseases in the Elderly (RIDE), the Netherlands Genomics Initiative, the Ministry of Education, Culture and Science, the Ministry of Health, Welfare and Sports, the European Commission (DG XII), and the Municipality of Rotterdam. Prof. Tiemeier was supported by the VIDI grant of ZonMw (2009-017.106.370). Dr. Ikram was supported by the VENI grant of NWO. The funders had no role in the study design or data collection and analysis.; SHIP; SHIP is part of the Community Medicine Research net of the University of Greifswald, Germany, which is funded by the Federal Ministry of Education and Research (grants no. 01ZZ9603, 01ZZ0103, and 01ZZ0403), the Ministry of Cultural Affairs as well as the Social Ministry of the Federal State of Mecklenburg-West Pomerania, and the network 'Greifswald Approach to Individualized Medicine (GANI_MED)' funded by the Federal Ministry of Education and Research (grant 03IS2061A). Genome-wide data have been supported by the Federal Ministry of Education and Research (grant no. 03ZIK012) and a joint grant from Siemens Healthcare, Erlangen, Germany and the Federal State of Mecklenburg-West Pomerania. The University of Greifswald is a member of the 'Center of Knowledge Interchange' program of the Siemens AG and the Cach, Campus program of the InterSystems GmbH. NR 15 TC 2 Z9 2 U1 2 U2 15 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1471-2156 J9 BMC GENET JI BMC Genet. PD DEC 29 PY 2014 VL 15 AR 159 DI 10.1186/s12863-014-0159-7 PG 7 WC Genetics & Heredity SC Genetics & Heredity GA AZ4ZM UT WOS:000348229900001 PM 25543667 ER PT J AU Hernandez, BY Goodman, MT Lynch, CF Cozen, W Unger, ER Steinau, M Thompson, T Saber, MS Altekruse, SF Lyu, C Saraiya, M AF Hernandez, Brenda Y. Goodman, Marc T. Lynch, Charles F. Cozen, Wendy Unger, Elizabeth R. Steinau, Martin Thompson, Trevor Saber, Maria Sibug Altekruse, Sean F. Lyu, Christopher Saraiya, Mona CA HPV Typing Canc Workgrp TI Human Papillomavirus Prevalence in Invasive Laryngeal Cancer in the United States SO PLOS ONE LA English DT Article ID SQUAMOUS-CELL CARCINOMA; OROPHARYNGEAL CANCER; NECK CANCERS; GENDER-DIFFERENCES; ORAL-CAVITY; PROGNOSTIC-SIGNIFICANCE; PHARYNGEAL CANCER; HPV-DNA; HEAD; SURVIVAL AB Purpose: Human papillomavirus (HPV) is a major risk factor for specific cancers of the head and neck, particularly malignancies of the tonsil and base of the tongue. However, the role of HPV in the development of laryngeal cancer has not been definitively established. We conducted a population-based, cancer registry study to evaluate and characterize the genotype-specific prevalence of HPV in invasive laryngeal cancer cases diagnosed in the U.S. Methods: The presence of genotype-specific HPV DNA was evaluated using the Linear Array HPV Genotyping Test and the INNO-LiPA HPV Genotyping Assay in formalin-fixed paraffin embedded tissue from 148 invasive laryngeal cancer cases diagnosed in 1993-2004 within the catchment area of three U. S. SEER cancer registries. Results: HPV DNA was detected in 31 of 148 (21%) invasive laryngeal cancers. Thirteen different genotypes were detected. Overall, HPV 16 and HPV 33 were the most commonly detected types. HPV was detected in 33% (9/27) of women compared with 18% (22/121) of men (p=0.08). After adjustment for age and year of diagnosis, female patients were more likely to have HPV-positive laryngeal tumors compared to males (adjusted OR 2.84, 95% CI 1.07-7.51). Viral genotype differences were also observed between the sexes. While HPV 16 and 18 constituted half of HPV-positive cases occurring in men, among women, only 1 was HPV 16 positive and none were positive for HPV 18. Overall 5-year survival did not vary by HPV status. Conclusions: HPV may be involved in the development of a subset of laryngeal cancers and its role may be more predominant in women compared to men. C1 [Hernandez, Brenda Y.] Univ Hawaii, Ctr Canc, Honolulu, HI 96822 USA. [Goodman, Marc T.] Cedars Sinai Med Ctr, Los Angeles, CA 90048 USA. [Lynch, Charles F.] Univ Iowa, Coll Publ Hlth, Dept Epidemiol, Iowa City, IA USA. [Cozen, Wendy; Saber, Maria Sibug] Univ So Calif, Kenneth Norris Jr Comprehens Canc Ctr, USC Keck Sch Med, Los Angeles, CA 90033 USA. [Cozen, Wendy; Saber, Maria Sibug] Univ So Calif, Dept Prevent Med, USC Keck Sch Med, Los Angeles, CA 90089 USA. [Cozen, Wendy; Saber, Maria Sibug] Univ So Calif, Dept Pathol, USC Keck Sch Med, Los Angeles, CA 90089 USA. [Unger, Elizabeth R.; Steinau, Martin] Ctr Dis Control & Prevent, Div High Consequence Pathogens & Pathol, Natl Ctr Emerging & Zoonot Infect Dis, Atlanta, GA USA. [Thompson, Trevor; Saraiya, Mona] Ctr Dis Control & Prevent, Div Canc Prevent & Control, Natl Ctr Chron Dis Prevent & Hlth Promot, Atlanta, GA USA. [Altekruse, Sean F.] NCI, Div Canc Control & Populat Sci, Rockville, MD USA. [Lyu, Christopher] Battelle Mem Inst, Durham, NC USA. RP Hernandez, BY (reprint author), Univ Hawaii, Ctr Canc, Honolulu, HI 96822 USA. EM brenda@cc.hawaii.edu FU Centers for Disease Control and Prevention (CDC); SEER Program; National Institutes of Health, Department of Health and Human Services [N01-PC-35139, N01-PC-35143, N01-PC-35137]; CDC intramural funds; Vaccine for Children Funds; California Department of Health Services, California Health and Safety [103885]; NationalCancer Institute, National Institutes of Health, Department of Health and Human Services [N01-PC-2010-00035]; Centers for Disease Control and Prevention [1U58DP000807-3] FX This project was supported in part by the Centers for Disease Control and Prevention (CDC) and the SEER Program, National Institutes of Health, Department of Health and Human Services, under Contracts N01-PC-35139 (Los Angeles), N01-PC-35143 (Iowa) and N01-PC-35137 (Hawaii). The support for coordination of genotyping data and genotyping was largely supported by CDC intramural funds and Vaccine for Children Funds. The collection of data from California was largely supported by the California Department of Health Services as part of the statewide cancer reporting program mandated by California Health and Safety Code Section 103885; by the NationalCancer Institute, National Institutes of Health, Department of Health and Human Services under Contract N01-PC-2010-00035; and cooperative agreement number 1U58DP000807-3 from the Centers for Disease Control and Prevention. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 51 TC 7 Z9 7 U1 1 U2 9 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA SN 1932-6203 J9 PLOS ONE JI PLoS One PD DEC 29 PY 2014 VL 9 IS 12 AR e115931 DI 10.1371/journal.pone.0115931 PG 14 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA AX7UN UT WOS:000347120200083 PM 25546150 ER PT J AU Zhao, ZZ Fan, HT Higgins, T Qi, J Haines, D Trivett, A Oppenheim, JJ Wei, H Li, J Lin, HS Howard, OMZ AF Zhao, Zhizheng Fan, Huiting Higgins, Tim Qi, Jia Haines, Diana Trivett, Anna Oppenheim, Joost J. Wei, Hou Li, Jie Lin, Hongsheng Howard, O. M. Zack TI Fufang Kushen injection inhibits sarcoma growth and tumor-induced hyperalgesia via TRPV1 signaling pathways SO CANCER LETTERS LA English DT Article DE Sarcoma; Hyperalgesia; TRPV1; ERK; Fufang Kushen injection ID ACTIVATED PROTEIN-KINASES; BONE CANCER PAIN; FACTOR-KAPPA-B; NUCLEAR-FACTOR; ANALGESIC ACTIVITY; INDUCED APOPTOSIS; ION-CHANNEL; SPINAL-CORD; RAT MODEL; CELLS AB Cancer pain is a deleterious consequence of tumor growth and related inflammation. Opioids and anti-inflammatory drugs provide first line treatment for cancer pain, but both are limited by side effects. Fufang Kushen injection (FKI) is GMP produced, traditional Chinese medicine used alone or with chemotherapy to reduce cancer-associated pain. FKI limited mouse sarcoma growth both in vivo and in vitro, in part, by reducing the phosphorylation of ERK and AKT kinases and BAD. FKI inhibited TRPV1 mediated capsaicin-induced ERK phosphorylation and reduced tumor-induced proinflammatory cytokine production. Thus, FKI limited cancer pain both directly by blocking TRPV1 signaling and indirectly by reducing tumor growth. Published by Elsevier Ireland Ltd. C1 [Zhao, Zhizheng; Fan, Huiting; Higgins, Tim; Trivett, Anna; Oppenheim, Joost J.; Howard, O. M. Zack] NCI, Mol Immunoregulat Lab, Canc & Inflammat Program, Ctr Canc Res, Ft Detrick, MD 21702 USA. [Zhao, Zhizheng; Fan, Huiting; Wei, Hou; Li, Jie; Lin, Hongsheng] China Acad Chinese Med Sci, Guang An Men Hosp, Beijing, Peoples R China. [Qi, Jia] NIDA, Neuronal Networks Sect, Intramural Res Program, NIH, Baltimore, MD 21224 USA. [Haines, Diana] Leidos Biomed, Frederick Natl Lab Canc Res, Frederick, MD 21702 USA. RP Howard, OMZ (reprint author), NCI, Mol Immunoregulat Lab, Canc & Inflammat Program, Ctr Canc Res, Ft Detrick, MD 21702 USA. EM howardz@mail.nih.gov FU NIH, National Cancer Institute, Center for Cancer Research [1 ZIA BC009369 23]; Ministry of Science and Technology of China [2006DFA31700]; National Natural Science Foundation of China [30600839, 30672764] FX This research was supported by the Intramural Research Program of the NIH, National Cancer Institute, Center for Cancer Research (grant No. 1 ZIA BC009369 23) and in part supported by grants No. 2006DFA31700 from the Ministry of Science and Technology of China and No. 30600839, No. 30672764 from National Natural Science Foundation of China. NR 55 TC 8 Z9 9 U1 4 U2 23 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0304-3835 EI 1872-7980 J9 CANCER LETT JI Cancer Lett. PD DEC 28 PY 2014 VL 355 IS 2 BP 232 EP 241 DI 10.1016/j.canlet.2014.08.037 PG 10 WC Oncology SC Oncology GA AS7IL UT WOS:000344430000009 PM 25242356 ER PT J AU Bai, XL Zhi, X Zhang, Q Liang, F Chen, W Liang, C Hu, QD Sun, X Zhuang, ZP Liang, TB AF Bai, Xueli Zhi, Xiao Zhang, Qi Liang, Feng Chen, Wei Liang, Chao Hu, Qida Sun, Xu Zhuang, Zhengping Liang, Tingbo TI Inhibition of protein phosphatase 2A sensitizes pancreatic cancer to chemotherapy by increasing drug perfusion via HIF-1 alpha-VEGF mediated angiogenesis SO CANCER LETTERS LA English DT Article DE Drug delivery; Chemotherapy sensitization; Angiogenesis; Vascular permeability; Xenograft model ID ENDOTHELIAL GROWTH-FACTOR; PHASE-III TRIAL; HEPATOCELLULAR-CARCINOMA; TUMOR-SUPPRESSOR; CELL-LINE; HYPOXIA; GEMCITABINE; PP2A; EXPRESSION; ENHANCEMENT AB Pancreatic cancer is a malignant disease without efficient treatment. Improved treatments are urgently needed to enhance or replace chemotherapy. Here we used a small molecular compound LB-100 to assess the effect of pharmacological inhibition of protein phosphatase 2A (PP2A) in combination with doxorubicin on the proliferation of pancreatic cancer in cell lines and a xenograft model. LB-100 moderately reduced PP2A activity and the growth of the cell lines but did not show chemosensitization in vitro. In vivo, however, LB-100 synergistically enhanced the activity of doxorubicin. This effect was associated with increased microvessel density, blood perfusion, and doxorubicin concentrations within the xenografts. Mechanically, LB-100 induced expression of hypoxia-induced factor-1 alpha (HIF-1 alpha) and vascular endothelial growth factor (VEGF). In an umbilical vein endothelial cell monolayer model for measuring changes in vascular permeability, increased VEGF secretion following exposure to LB-100 and doxorubicin was accompanied by increased amounts of doxorubicin penetrating the endothelial barrier. In conclusion, PP2A inhibition by LB-100 enhanced the cytotoxicity of doxorubicin in vivo but not in vitro potentially via HIF-1 alpha-VEGF mediated angiogenesis. Combining inhibition of PP2A with chemotherapeutic regimens may enhance their effectiveness against pancreatic cancer. (C) 2014 Elsevier Ireland Ltd. All rights reserved. C1 [Bai, Xueli; Zhi, Xiao; Zhang, Qi; Chen, Wei; Liang, Chao; Hu, Qida; Sun, Xu; Liang, Tingbo] Zhejiang Univ, Sch Med, Affiliated Hosp 2, Dept Hepatobiliary & Pancreat Surg, Hangzhou 310003, Zhejiang, Peoples R China. [Bai, Xueli; Zhang, Qi; Liang, Tingbo] Zhejiang Univ, Sch Med, Affiliated Hosp 2, Key Lab Canc Prevent & Intervent, Hangzhou 310003, Zhejiang, Peoples R China. [Liang, Feng] Zhejiang Univ, Sch Med, Affiliated Hosp 2, Dept Neurosurg, Hangzhou 310003, Zhejiang, Peoples R China. [Zhuang, Zhengping] NINDS, NIH, Bethesda, MD 20892 USA. RP Liang, TB (reprint author), Zhejiang Univ, Sch Med, Affiliated Hosp 2, Dept Hepatobiliary & Pancreat Surg, Hangzhou 310003, Zhejiang, Peoples R China. EM liangtingbo@zju.edu.cn RI Hu, Qida/B-4558-2009 OI Hu, Qida/0000-0002-9092-7808 FU National Natural Science Foundation of China [81171884]; National Key Basic Research Program of China [2014CB542101]; Traditional Medicine Science & Technology Research Program of Zhejiang [2014ZZ007]; Department of Health of Zhejiang; Science & Technology Innovation Team of Zhejiang FX We thank Lixte Biotechnology Holdings, Inc. (East Setauket, NY, USA) for the gift of LB-100. This study was financially supported by the National Natural Science Foundation of China (No. 81171884), the National Key Basic Research Program of China (No. 2014CB542101), the Traditional Medicine Science & Technology Research Program of Zhejiang (2014ZZ007), the Innovation and High-Level Talent Training Program of Department of Health of Zhejiang, and the Science & Technology Innovation Team of Zhejiang. We appreciate Mr. Hu Liqiang (The Second Affiliated Hospital, Zhejiang University School of Medicine, China) for his great help in certain experiments. NR 33 TC 11 Z9 11 U1 4 U2 47 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0304-3835 EI 1872-7980 J9 CANCER LETT JI Cancer Lett. PD DEC 28 PY 2014 VL 355 IS 2 BP 281 EP 287 DI 10.1016/j.canlet.2014.09.048 PG 7 WC Oncology SC Oncology GA AS7IL UT WOS:000344430000014 PM 25304380 ER PT J AU Franceschini, N Hu, YJ Reiner, AP Buyske, S Nalls, M Yanek, LR Li, Y Hindorff, LA Cole, SA Howard, BV Stafford, JM Carty, CL Sethupathy, P Martin, LW Lin, DY Johnson, KC Becker, LC North, KE Dehghan, A Bis, JC Liu, YM Greenland, P Manson, JE Maeda, N Garcia, M Harris, TB Becker, DM O'Donnell, C Heiss, G Kooperberg, C Boerwinkle, E AF Franceschini, Nora Hu, Yijuan Reiner, Alex P. Buyske, Steven Nalls, Mike Yanek, Lisa R. Li, Yun Hindorff, Lucia A. Cole, Shelley A. Howard, Barbara V. Stafford, Jeanette M. Carty, Cara L. Sethupathy, Praveen Martin, Lisa W. Lin, Dan-Yu Johnson, Karen C. Becker, Lewis C. North, Kari E. Dehghan, Abbas Bis, Joshua C. Liu, Yongmei Greenland, Philip Manson, JoAnn E. Maeda, Nobuyo Garcia, Melissa Harris, Tamara B. Becker, Diane M. O'Donnell, Christopher Heiss, Gerardo Kooperberg, Charles Boerwinkle, Eric TI Prospective Associations of Coronary Heart Disease Loci in African Americans Using the MetaboChip: The PAGE Study SO PLOS ONE LA English DT Article ID GENOME-WIDE ASSOCIATION; ARTERY-DISEASE; MYOCARDIAL-INFARCTION; SUSCEPTIBILITY LOCUS; BLOOD-PRESSURE; CELL-CYCLE; VARIANTS; HEALTH; RISK; METAANALYSIS AB Background: Coronary heart disease (CHD) is a leading cause of morbidity and mortality in African Americans. However, there is a paucity of studies assessing genetic determinants of CHD in African Americans. We examined the association of published variants in CHD loci with incident CHD, attempted to fine map these loci, and characterize novel variants influencing CHD risk in African Americans. Methods and Results: Up to 8,201 African Americans (including 546 first CHD events) were genotyped using the MetaboChip array in the Atherosclerosis Risk in Communities (ARIC) study and Women's Health Initiative (WHI). We tested associations using Cox proportional hazard models in sex-and study-stratified analyses and combined results using meta-analysis. Among 44 validated CHD loci available in the array, we replicated and fine-mapped the SORT1 locus, and showed same direction of effects as reported in studies of individuals of European ancestry for SNPs in 22 additional published loci. We also identified a SNP achieving array wide significance (MYC: rs2070583, allele frequency 0.02, P=8.1x10(-8)), but the association did not replicate in an additional 8,059 African Americans (577 events) from the WHI, HealthABC and GeneSTAR studies, and in a meta-analysis of 5 cohort studies of European ancestry (24,024 individuals including 1,570 cases of MI and 2,406 cases of CHD) from the CHARGE Consortium. Conclusions: Our findings suggest that some CHD loci previously identified in individuals of European ancestry may be relevant to incident CHD in African Americans. C1 [Franceschini, Nora; North, Kari E.; Heiss, Gerardo] Univ N Carolina, Gillings Sch Global Publ Hlth, Chapel Hill, NC 27514 USA. [Hu, Yijuan] Emory Univ, Dept Biostat & Bioinformat, Atlanta, GA 30322 USA. [Reiner, Alex P.] Univ Washington, Dept Epidemiol, Seattle, WA 98195 USA. [Buyske, Steven] Rutgers State Univ, Dept Stat & Biostat, Piscataway, NJ USA. [Nalls, Mike] NIA, Neurogenet Lab, NIH, Bethesda, MD 20892 USA. [Yanek, Lisa R.; Becker, Lewis C.; Becker, Diane M.] Johns Hopkins Univ, Sch Med, Dept Med, Div Gen Internal Med, Baltimore, MD 21205 USA. [Li, Yun; Lin, Dan-Yu] Univ N Carolina, Dept Biostat, Chapel Hill, NC USA. [Hindorff, Lucia A.] NHGRI, Div Gen Med, NIH, Bethesda, MD USA. [Cole, Shelley A.] SW Fdn Biomed Res, Dept Genet, San Antonio, TX USA. [Howard, Barbara V.] MedStar Hlth Res Inst, Hyattsville, MD USA. [Reiner, Alex P.; Stafford, Jeanette M.] Wake Forest Univ, Bowman Gray Sch Med, Dept Biostat Sci, Winston Salem, NC USA. [Carty, Cara L.; Kooperberg, Charles] Fred Hutchinson Canc Res Ctr, Div Publ Hlth Sci, Seattle, WA 98104 USA. [Sethupathy, Praveen] Univ N Carolina, Lineberger Comprehens Canc Ctr, Sch Med, Dept Genet, Chapel Hill, NC 27599 USA. [Martin, Lisa W.] George Washington Univ, Cardiovasc Inst, Washington, DC USA. [Johnson, Karen C.] Univ Tennessee, Ctr Hlth Sci, Dept Prevent Med, Memphis, TN 38163 USA. [North, Kari E.] UNC, Ctr Genome Sci, Chapel Hill, NC USA. [Dehghan, Abbas] Erasmus Univ, Med Ctr, Dept Epidemiol, Rotterdam, Netherlands. [Bis, Joshua C.] Univ Washington, Cardiovasc Hlth Res Unit, Seattle, WA 98195 USA. [Bis, Joshua C.] Univ Washington, Dept Med, Seattle, WA 98195 USA. [Liu, Yongmei] Wake Forest Univ, Sch Med, Ctr Human Gen, Dept Epidemiol & Prevent, Winston Salem, NC 27109 USA. [Greenland, Philip] Northwestern Univ, Dept Prevent Med, Chicago, IL 60611 USA. [Greenland, Philip] Northwestern Univ, Dept Med, Chicago, IL 60611 USA. [Manson, JoAnn E.] Harvard Univ, Sch Med, Brigham & Womens Hosp, Dept Med, Boston, MA USA. [Maeda, Nobuyo] Univ N Carolina, Dept Pathol, Chapel Hill, NC USA. [Maeda, Nobuyo] Univ N Carolina, Lab Med, Chapel Hill, NC USA. [Garcia, Melissa; Harris, Tamara B.] NIA, Lab Epidemiol & Populat Sci, NIH, Bethesda, MD 20892 USA. [Becker, Diane M.] Johns Hopkins Univ, Bloomberg Sch Publ Hlth, Dept Hlth Policy & Management, Baltimore, MD USA. [O'Donnell, Christopher] Lung & Blood Inst, Framingham Heart Study, Framingham, MA USA. [Boerwinkle, Eric] Univ Texas Hlth Sci Ctr Houston, Ctr Human Genet, Houston, TX 77030 USA. RP Franceschini, N (reprint author), Univ N Carolina, Gillings Sch Global Publ Hlth, Chapel Hill, NC 27514 USA. EM noraf@unc.edu OI Buyske, Steven/0000-0001-8539-5416; Dehghan, Abbas/0000-0001-6403-016X FU National Human Genome Research Institute (NHGRI); CALiCo [U01HG004803]; EAGLE [U01HG004798]; MEC [U01HG004802]; WHI [U01HG004790]; Coordinating Center [U01HG004801]; National Heart, Lung, and Blood Institute contracts [HHSN268201100005C, HHSN268201100006C, HHSN268201100007C, HHSN268201100008C, HSN268201100009C, HHSN268201100010C, HHSN268201100011C, HHSN268201100012C, R01HL087641, R01HL59367, R01HL086694]; National Human Genome Research Institute [U01HG004402]; National Institutes of Health [HHSN268200625226C, HHSN268200782096C]; National Institutes of Health and NIH Roadmap for Medical Research [UL1RR025005]; National Heart, Lung, and Blood Institute, National Institutes of Health, U.S. Department of Health and Human Services [N01WH22110, 24152, 32100-2, 32105-6, 32108-9, 32111-13, 32115, 32118-32119, 32122, 42107-26, 42129-32, 44221]; NIA [N01AG62101, N01AG62103, N01AG62106, 1R01AG032098-01A1]; Intramural Research Program of the NIH, National Institute on Aging [Z01 AG000949-02, Z01 AG007390-07]; National Institutes of Health, Bethesda, Maryland [U01 HL72518, HL097698, HL59684, HL58625-01A1, HL071025-01A1, NR0224103, NR008153-01, M01 RR00052]; [R21HL123677-01] FX The Population Architecture Using Genomics and Epidemiology (PAGE) program is funded by the National Human Genome Research Institute (NHGRI), supported by U01HG004803 (CALiCo), U01HG004798 (EAGLE), U01HG004802 (MEC), U01HG004790 (WHI), and U01HG004801 (Coordinating Center), and their respective NHGRI ARRA supplements. The contents of this paper are solely the responsibility of the authors and do not necessarily represent the official views of the NIH. The complete list of PAGE members can be found at http://www.pagestudy.org. The Atherosclerosis Risk in Communities Study is carried out as a collaborative study supported by National Heart, Lung, and Blood Institute contracts (HHSN268201100005C, HHSN268201100006C, HHSN268201100007C, HHSN268201100008C, HSN268201100009C, HHSN268201100010C, HHSN268201100011C, and HHSN268201100012C), R01HL087641, R01HL59367 and R01HL086694; National Human Genome Research Institute contract U01HG004402; and National Institutes of Health contract HHSN268200625226C. NF is supported by R21HL123677-01. The authors thank the staff and participants of the ARIC study for their important contributions. Infrastructure was partly supported by Grant Number UL1RR025005, a component of the National Institutes of Health and NIH Roadmap for Medical Research. The WHI program is funded by the National Heart, Lung, and Blood Institute, National Institutes of Health, U.S. Department of Health and Human Services through contracts N01WH22110, 24152, 32100-2, 32105-6, 32108-9, 32111-13, 32115, 32118-32119, 32122, 42107-26, 42129-32, and 44221. This manuscript was prepared in collaboration with investigators of the WHI, and has been approved by the WHI. WHI investigators are listed at http://www.whiscience.org/publications/WHI_investigators_shortlist.pdf. HealthABC was supported by NIA contracts N01AG62101, N01AG62103, and N01AG62106 and was supported in part by the Intramural Research Program of the NIH, National Institute on Aging (Z01 AG000949-02 and Z01 AG007390-07, Human subjects protocol UCSF IRB is H5254-12688- 11). The genome-wide association study was funded by NIA grant 1R01AG032098-01A1 to Wake Forest University Health Sciences and genotyping services were provided by the Center for Inherited Disease Research (CIDR). CIDR is fully funded through a federal contract from the National Institutes of Health to The Johns Hopkins University, contract number HHSN268200782096C. 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). GeneSTAR was supported in part by grants U01 HL72518, HL097698, HL59684, HL58625-01A1, HL071025-01A1, NR0224103, NR008153-01 from the National Institutes of Health, Bethesda, Maryland, and grant M01 RR00052 from the National Institutes of Health, Bethesda, Maryland, to the Johns Hopkins University School of Medicine General Clinical Research Center. NR 40 TC 4 Z9 4 U1 2 U2 8 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 26 PY 2014 VL 9 IS 12 AR e113203 DI 10.1371/journal.pone.0113203 PG 18 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA AX9RO UT WOS:000347239900006 PM 25542012 ER PT J AU Hobbs, CV Dixit, S Penzak, SR Sahu, T Orr-Gonzalez, S Lambert, L Zeleski, K Chen, JY Neal, J Borkowsky, W Wu, YM Duffy, PE AF Hobbs, Charlotte V. Dixit, Saurabh Penzak, Scott R. Sahu, Tejram Orr-Gonzalez, Sachy Lambert, Lynn Zeleski, Katie Chen, Jingyang Neal, Jillian Borkowsky, William Wu, Yimin Duffy, Patrick E. TI Neither the HIV Protease Inhibitor Lopinavir-Ritonavir nor the Antimicrobial Trimethoprim-Sulfamethoxazole Prevent Malaria Relapse in Plasmodium cynomolgi-Infected Non-Human Primates SO PLOS ONE LA English DT Article ID ANTIMALARIAL-DRUGS; RHESUS-MONKEYS; MACACA-MULATTA; LIVER STAGES; IN-VITRO; PHARMACOKINETICS; HYPNOZOITE; FALCIPARUM; QUININE; VIVAX AB Plasmodium vivax malaria causes significant morbidity and mortality worldwide, and only one drug is in clinical use that can kill the hypnozoites that cause P. vivax relapses. HIV and P. vivax malaria geographically overlap in many areas of the world, including South America and Asia. Despite the increasing body of knowledge regarding HIV protease inhibitors (HIV PIs) on P. falciparum malaria, there are no data regarding the effects of these treatments on P. vivax's hypnozoite form and clinical relapses of malaria. We have previously shown that the HIV protease inhibitor lopinavir-ritonavir (LPV-RTV) and the antibiotic trimethoprim sulfamethoxazole (TMP-SMX) inhibit Plasmodium actively dividing liver stages in rodent malarias and in vitro in P. falciparum, but effect against Plasmodium dormant hypnozoite forms remains untested. Separately, although other antifolates have been tested against hypnozoites, the antibiotic trimethoprim sulfamethoxazole, commonly used in HIV infection and exposure management, has not been evaluated for hypnozoite-killing activity. Since Plasmodium cynomolgi is an established animal model for the study of liver stages of malaria as a surrogate for P. vivax infection, we investigated the antimalarial activity of these drugs on Plasmodium cynomolgi relapsing malaria in rhesus macaques. Herein, we demonstrate that neither TMP-SMX nor LPV-RTV kills hypnozoite parasite liver stage forms at the doses tested. Because HIV and malaria geographically overlap, and more patients are being managed for HIV infection and exposure, understanding HIV drug impact on malaria infection is important. C1 [Hobbs, Charlotte V.; Dixit, Saurabh; Sahu, Tejram; Orr-Gonzalez, Sachy; Lambert, Lynn; Zeleski, Katie; Chen, Jingyang; Neal, Jillian; Wu, Yimin; Duffy, Patrick E.] NIAID, Lab Malaria Immunol & Vaccinol, NIH, Rockville, MD 20852 USA. [Penzak, Scott R.] Univ North Texas Syst Coll Pharm, Dept Pharmacotherapy, Ft Worth, TX 76107 USA. [Borkowsky, William] NYU, Dept Pediat, Sch Med, Div Infect Dis & Immunol, New York, NY 10016 USA. RP Hobbs, CV (reprint author), NIAID, Lab Malaria Immunol & Vaccinol, NIH, Rockville, MD 20852 USA. EM charlotte.hobbs@nih.gov OI Sahu, Tejram/0000-0002-0912-7660 FU National Institutes of Health Division of Intramural Research FX Funding: This work was supported by the National Institutes of Health Division of Intramural Research. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 49 TC 2 Z9 2 U1 3 U2 7 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA SN 1932-6203 J9 PLOS ONE JI PLoS One PD DEC 26 PY 2014 VL 9 IS 12 AR e115506 DI 10.1371/journal.pone.0115506 PG 12 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA AX9RO UT WOS:000347239900048 PM 25541998 ER PT J AU Klein, JD Sherrill, JB Morello, GM Miguel, PJS Ding, ZM Liangpunsakul, S Liang, TB Muir, WM Lumeng, L Lossie, AC AF Klein, Jonathon D. Sherrill, Jeremy B. Morello, Gabriella M. Miguel, Phillip J. San Ding, Zhenming Liangpunsakul, Suthat Liang, Tiebing Muir, William M. Lumeng, Lawrence Lossie, Amy C. TI A Snapshot of the Hepatic Transcriptome: Ad Libitum Alcohol Intake Suppresses Expression of Cholesterol Synthesis Genes in Alcohol-Preferring (P) Rats SO PLOS ONE LA English DT Article ID CORONARY-HEART-DISEASE; LIVER-DISEASE; MULTIPLE CONCENTRATIONS; CARDIOVASCULAR-DISEASE; INTRAGASTRIC INFUSION; SINGLE CONCENTRATION; CONCURRENT ACCESS; ETHANOL TREATMENT; MESSENGER-RNA; METABOLISM AB Research is uncovering the genetic and biochemical effects of consuming large quantities of alcohol. One prime example is the J- or U-shaped relationship between the levels of alcohol consumption and the risk of atherosclerotic cardiovascular disease. Moderate alcohol consumption in humans (about 30 g ethanol/d) is associated with reduced risk of coronary heart disease, while abstinence and heavier alcohol intake is linked to increased risk. However, the hepatic consequences of moderate alcohol drinking are largely unknown. Previous data from alcohol-preferring (P) rats showed that chronic consumption does not produce significant hepatic steatosis in this well-established model. Therefore, free-choice alcohol drinking in P rats may mimic low risk or nonhazardous drinking in humans, and chronic exposure in P animals can illuminate the molecular underpinnings of free-choice drinking in the liver. To address this gap, we captured the global, steady-state liver transcriptome following a 23 week free-choice, moderate alcohol consumption regimen (similar to 7.43 g ethanol/kg/day) in inbred alcoholpreferring (iP10a) rats. Chronic consumption led to down-regulation of nine genes in the cholesterol biosynthesis pathway, including HMG-CoA reductase, the rate-limiting step for cholesterol synthesis. These findings corroborate our phenotypic analyses, which indicate that this paradigm produced animals whose hepatic triglyceride levels, cholesterol levels and liver histology were indistinguishable from controls. These findings explain, at least in part, the J- or U-shaped relationship between cardiovascular risk and alcohol intake, and provide outstanding candidates for future studies aimed at understanding the mechanisms that underlie the salutary cardiovascular benefits of chronic low risk and nonhazardous alcohol intake. C1 [Klein, Jonathon D.; Muir, William M.; Lossie, Amy C.] Purdue Univ, Interdisciplinary Life Sci Grad Program, W Lafayette, IN 47907 USA. [Klein, Jonathon D.; Sherrill, Jeremy B.; Morello, Gabriella M.; Muir, William M.; Lossie, Amy C.] Purdue Univ, Dept Anim Sci, W Lafayette, IN 47907 USA. Purdue Univ, Core Facil, W Lafayette, IN 47907 USA. [Miguel, Phillip J. San] Purdue Univ, Dept Hort & Landscape Architecture, W Lafayette, IN 47907 USA. [Ding, Zhenming] Indiana Univ, Sch Med, Dept Psychiat, Indianapolis, IN 46202 USA. [Liangpunsakul, Suthat; Liang, Tiebing; Muir, William M.; Lumeng, Lawrence; Lossie, Amy C.] Indiana Univ, Sch Med, Dept Med, Indianapolis, IN USA. RP Lossie, AC (reprint author), NIH, Off Behav & Social Sci Res, Off Director, Bldg 10, Bethesda, MD 20892 USA. EM amy.lossie@nih.gov RI SanMiguel, Phillip/I-2196-2015 OI SanMiguel, Phillip/0000-0002-3742-9527 FU National Center for Advancing Translational Science [UL1TR00110801]; National Institute on Alcohol Abuse and Alcoholism [R24 AA015512 06, R24 AA015512 06S1, P60 AA007611 24] FX This study was funded by grant numbers: UL1TR00110801 (National Center for Advancing Translational Science; http://www.ncats.nih.gov) to ACL and LL; R24 AA015512 06, R24 AA015512 06S1 and P60 AA007611 24 (National Institute on Alcohol Abuse and Alcoholism; http://www.niaaa.nih.gov) to LL. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 54 TC 1 Z9 1 U1 1 U2 8 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 26 PY 2014 VL 9 IS 12 AR e110501 DI 10.1371/journal.pone.0110501 PG 23 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA AX9RO UT WOS:000347239900003 PM 25542004 ER PT J AU Ohno, M Kanayama, T Moore, R Ray, M Negishi, M AF Ohno, Marumi Kanayama, Tomohiko Moore, Rick Ray, Manas Negishi, Masahiko TI The Roles of Co-Chaperone CCRP/DNAJC7 in Cyp2b10 Gene Activation and Steatosis Development in Mouse Livers SO PLOS ONE LA English DT Article ID NUCLEAR RECEPTOR CAR; ARYL-HYDROCARBON RECEPTOR; CONSTITUTIVE ACTIVE/ANDROSTANE RECEPTOR; X-ASSOCIATED PROTEIN-2; INTERACTING PROTEIN; J-DOMAIN; INDUCTION; COMPLEX; EXPRESSION; ELEMENTS AB Cytoplasmic constitutive active/androstane receptor (CAR) retention protein (CCRP and also known as DNAJC7) is a co-chaperone previously characterized to retain nuclear receptor CAR in the cytoplasm of HepG2 cells. Here we have produced CCRP knockout (KO) mice and demonstrated that CCRP regulates CAR at multiple steps in activation of the cytochrome (Cyp) 2b10 gene in liver: nuclear accumulation, RNA polymerase II recruitment and epigenetic modifications. Phenobarbital treatment greatly increased nuclear CAR accumulation in the livers of KO males as compared to those of wild type (WT) males. Despite this accumulation, phenobarbital-induced activation of the Cyp2b10 gene was significantly attenuated. In ChIP assays, a CAR/retinoid X receptor-alpha (RXRa) heterodimer binding to the Cyp2b10 promoter was already increased before phenobarbital treatment and further pronounced after treatment. However, RNA polymerase II was barely recruited to the promoter even after phenobarbital treatment. Histone H3K27 on the Cyp2b10 promoter was de-methylated only after phenobarbital treatment in WT but was fully de-methylated before treatment in KO males. Thus, CCRP confers phenobarbital-induced de-methylation capability to the promoter as well as the phenobarbital responsiveness of recruiting RNA polymerase II, but is not responsible for the binding between CAR and its cognate sequence, phenobarbital responsive element module. In addition, KO males developed steatotic livers and increased serum levels of total cholesterol and high density lipoprotein in response to fasting. CCRP appears to be involved in various hepatic regulations far beyond CAR-mediated drug metabolism. C1 [Ohno, Marumi; Kanayama, Tomohiko; Moore, Rick; Negishi, Masahiko] NIEHS, Pharmacogenet Sect, Reprod & Dev Biol Lab, NIH, Res Triangle Pk, NC 27709 USA. [Ray, Manas] NIEHS, Knockout Core, NIH, Res Triangle Pk, NC 27709 USA. RP Negishi, M (reprint author), NIEHS, Pharmacogenet Sect, Reprod & Dev Biol Lab, NIH, POB 12233, Res Triangle Pk, NC 27709 USA. EM negishi@niehs.nih.gov FU National Institutes of Health [Z01ES1005-01] FX This work was supported by National Institutes of Health Intramural Research program:: Z01ES1005-01. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 43 TC 4 Z9 4 U1 1 U2 7 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA SN 1932-6203 J9 PLOS ONE JI PLoS One PD DEC 26 PY 2014 VL 9 IS 12 AR e115663 DI 10.1371/journal.pone.0115663 PG 18 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA AX9RO UT WOS:000347239900066 PM 25542016 ER PT J AU Wright, DW Yeatts, SD Silbergleit, R Palesch, YY Hertzberg, VS Frankel, M Goldstein, FC Caveney, AF Howlett-Smith, H Bengelink, EM Manley, GT Merck, LH Janis, LS Barsan, WG AF Wright, David W. Yeatts, Sharon D. Silbergleit, Robert Palesch, Yuko Y. Hertzberg, Vicki S. Frankel, Michael Goldstein, Felicia C. Caveney, Angela F. Howlett-Smith, Harriet Bengelink, Erin M. Manley, Geoffrey T. Merck, Lisa H. Janis, L. Scott Barsan, William G. CA NETT Investigators TI Very Early Administration of Progesterone for Acute Traumatic Brain Injury SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Article ID CLINICAL-TRIALS; PRACTICAL SCALE; NEUROPROTECTION; COMA AB BACKGROUND Traumatic brain injury (TBI) is a major cause of death and disability worldwide. Progesterone has been shown to improve neurologic outcome in multiple experimental models and two early-phase trials involving patients with TBI. METHODS We conducted a double-blind, multicenter clinical trial in which patients with severe, moderate-to-severe, or moderate acute TBI (Glasgow Coma Scale score of 4 to 12, on a scale from 3 to 15, with lower scores indicating a lower level of consciousness) were randomly assigned to intravenous progesterone or placebo, with the study treatment initiated within 4 hours after injury and administered for a total of 96 hours. Efficacy was defined as an increase of 10 percentage points in the proportion of patients with a favorable outcome, as determined with the use of the stratified dichotomy of the Extended Glasgow Outcome Scale score at 6 months after injury. Secondary outcomes included mortality and the Disability Rating Scale score. RESULTS A total of 882 of the planned sample of 1140 patients underwent randomization before the trial was stopped for futility with respect to the primary outcome. The study groups were similar with regard to baseline characteristics; the median age of the patients was 35 years, 73.7% were men, 15.2% were black, and the mean Injury Severity Score was 24.4 (on a scale from 0 to 75, with higher scores indicating greater severity). The most frequent mechanism of injury was a motor vehicle accident. There was no significant difference between the progesterone group and the placebo group in the proportion of patients with a favorable outcome (relative benefit of progesterone, 0.95; 95% confidence interval [CI], 0.85 to 1.06; P = 0.35). Phlebitis or thrombophlebitis was more frequent in the progesterone group than in the placebo group (relative risk, 3.03; CI, 1.96 to 4.66). There were no significant differences in the other prespecified safety outcomes. CONCLUSIONS This clinical trial did not show a benefit of progesterone over placebo in the improvement of outcomes in patients with acute TBI. C1 [Wright, David W.; Howlett-Smith, Harriet] Emory Univ, Sch Med, Dept Emergency Med, Atlanta, GA USA. [Frankel, Michael; Goldstein, Felicia C.] Emory Univ, Sch Med, Dept Neurol, Atlanta, GA 30322 USA. Grady Mem Hosp, Atlanta, GA USA. [Hertzberg, Vicki S.] Emory Univ, Dept Biostat, Rollins Sch Publ Hlth, Atlanta, GA 30322 USA. [Yeatts, Sharon D.; Palesch, Yuko Y.] Med Univ S Carolina, Dept Publ Hlth Sci, Charleston, SC USA. [Silbergleit, Robert; Bengelink, Erin M.; Barsan, William G.] Univ Michigan, Dept Emergency Med, Ann Arbor, MI 48109 USA. [Caveney, Angela F.] Univ Michigan, Dept Psychiat, Ann Arbor, MI 48109 USA. [Manley, Geoffrey T.] Univ Calif San Francisco, Dept Neurosurg, San Francisco, CA USA. [Merck, Lisa H.] Brown Univ, Dept Emergency Med, Warren Alpert Med Sch, Providence, RI 02912 USA. [Janis, L. Scott] NINDS, NIH, Bethesda, MD 20892 USA. RP Wright, DW (reprint author), 49 Jesse Hill Jr Dr, Atlanta, GA 30303 USA. EM david.wright@emory.edu FU National Institute of Neurological Disorders and Stroke of the National Institutes of Health [NS062778, 5U10NS059032, U01NS056975]; National Center for Advancing Translational Sciences of the National Institutes of Health [UL1TR000454]; Emory Emergency Neurosciences Laboratory in the Department of Emergency Medicine, Emory School of Medicine; Grady Memorial Hospital FX Supported by grants from the National Institute of Neurological Disorders and Stroke of the National Institutes of Health (NS062778, 5U10NS059032, and U01NS056975) and the National Center for Advancing Translational Sciences of the National Institutes of Health (UL1TR000454) and by the Emory Emergency Neurosciences Laboratory in the Department of Emergency Medicine, Emory School of Medicine, and Grady Memorial Hospital. NR 17 TC 109 Z9 114 U1 2 U2 14 PU MASSACHUSETTS MEDICAL SOC PI WALTHAM PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA SN 0028-4793 EI 1533-4406 J9 NEW ENGL J MED JI N. Engl. J. Med. PD DEC 25 PY 2014 VL 371 IS 26 BP 2457 EP 2466 DI 10.1056/NEJMoa1404304 PG 10 WC Medicine, General & Internal SC General & Internal Medicine GA AX4RZ UT WOS:000346920300005 PM 25493974 ER PT J AU Ouyang, Q Wang, LR Mu, Y Xie, XQ AF Ouyang, Qin Wang, Lirong Mu, Ying Xie, Xiang-Qun TI Modeling skin sensitization potential of mechanistically hard-to-be-classified aniline and phenol compounds with quantum mechanistic properties SO BMC PHARMACOLOGY & TOXICOLOGY LA English DT Article DE Chemical mechanisms; Structure-activity relationship; Skin sensitizer; Anilines; Phenols; Quantum mechanism ID LYMPH-NODE ASSAY; CONTACT ALLERGENS; KNOWLEDGE GENERATION; METABOLIC-ACTIVATION; RISK-ASSESSMENT; IN-VITRO; PREDICTION; REACTIVITY; TOXICITY; POTENCY AB Background: Advanced structure-activity relationship (SAR) modeling can be used as an alternative tool for identification of skin sensitizers and in improvement of the medical diagnosis and more effective practical measures to reduce the causative chemical exposures. It can also circumvent ethical concern of using animals in toxicological tests, and reduce time and cost. Compounds with aniline or phenol moieties represent two large classes of frequently skin sensitizing chemicals but exhibiting very variable, and difficult to predict, potency. The mechanisms of action are not well-understood. Methods: A group of mechanistically hard-to-be-classified aniline and phenol chemicals were collected. An in silico model was established by statistical analysis of quantum descriptors for the determination of the relationship between their chemical structures and skin sensitization potential. The sensitization mechanisms were investigated based on the features of the established model. Then the model was utilized to analyze a subset of FDA approved drugs containing aniline and/or phenol groups for prediction of their skin sensitization potential. Results and discussion: A linear discriminant model using the energy of the highest occupied molecular orbital (epsilon(HOMO)) as the descriptor yielded high prediction accuracy. The contribution of epsilon(HOMO) as a major determinant may suggest that autoxidation or free radical binding could be involved. The model was further applied to predict allergic potential of a subset of FDA approved drugs containing aniline and/or phenol moiety. The predictions imply that similar mechanisms (autoxidation or free radical binding) may also play a role in the skin sensitization caused by these drugs. Conclusions: An accurate and simple quantum mechanistic model has been developed to predict the skin sensitization potential of mechanistically hard-to-be-classified aniline and phenol chemicals. The model could be useful for the skin sensitization potential predictions of a subset of FDA approved drugs. C1 [Ouyang, Qin; Wang, Lirong; Xie, Xiang-Qun] Univ Pittsburgh, Sch Pharm,Dept Pharmaceut Sci,Drug Discovery Inst, Natl Ctr Excellence Computat Drug Abuse Res, Computat Chem Genom Screening Ctr,NIH, Pittsburgh, PA 15261 USA. [Xie, Xiang-Qun] Univ Pittsburgh, Dept Computat & Syst Biol, Pittsburgh, PA 15261 USA. [Mu, Ying] US FDA, Div Biol, Off Sci & Engn Labs, Ctr Devices & Radiobiol Hlth, Silver Spring, MD 20993 USA. [Ouyang, Qin] Third Mil Med Univ, Coll Pharm, Chongqing 400038, Peoples R China. RP Xie, XQ (reprint author), Univ Pittsburgh, Sch Pharm,Dept Pharmaceut Sci,Drug Discovery Inst, Natl Ctr Excellence Computat Drug Abuse Res, Computat Chem Genom Screening Ctr,NIH, 718 Salk Hall, Pittsburgh, PA 15261 USA. EM xix15@pitt.edu FU National Natural Science Foundation of China [NSFC21202201] FX OQ would like to acknowledge the support from the National Natural Science Foundation of China (NSFC21202201). NR 45 TC 1 Z9 1 U1 2 U2 5 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1471-2210 J9 BMC PHARMACOL TOXICO JI BMC Pharmacol. Toxicol. PD DEC 24 PY 2014 VL 15 AR 76 DI 10.1186/2050-6511-15-76 PG 9 WC Pharmacology & Pharmacy; Toxicology SC Pharmacology & Pharmacy; Toxicology GA AZ3UL UT WOS:000348152000001 PM 25539579 ER PT J AU Nussinov, R Tsai, CJ Liu, J AF Nussinov, Ruth Tsai, Chung-Jung Liu, Jin TI Principles of Allosteric Interactions in Cell Signaling SO JOURNAL OF THE AMERICAN CHEMICAL SOCIETY LA English DT Article ID CONFORMATIONAL SELECTION; POPULATION-SHIFT; PROTEIN FUNCTION; INDUCED FIT; COMMUNICATION PATHWAYS; MOLECULAR RECOGNITION; RECEPTOR ACTIVATION; RESPONSE ELEMENTS; ENERGY LANDSCAPES; NMR-SPECTROSCOPY AB Linking cell signaling events to the fundamental physicochemical basis of the conformational behavior of single molecules and ultimately to cellular function is a key challenge facing the life sciences. Here we outline the emerging principles of allosteric interactions in cell signaling, with emphasis on the following points. (1) Allosteric efficacy is not a function of the chemical composition of the allosteric pocket but reflects the extent of the population shift between the inactive and active states. That is, the allosteric effect is determined by the extent of preferred binding, not by the overall binding affinity. (2) Coupling between the allosteric and active sites does not decide the allosteric effect; however, it does define the propagation pathways, the allosteric binding sites, and key on-path residues. (3) Atoms of allosteric effectors can act as driver or anchor and create attractive pulling or repulsive pushing interactions. Deciphering, quantifying, and integrating the multiple co-occurring events present daunting challenges to our scientific community. C1 [Nussinov, Ruth; Tsai, Chung-Jung] NCI, Canc & Inflammat Program, Leidos Biomed Res Inc, Frederick Natl Lab Canc Res, Frederick, MD 21702 USA. [Nussinov, Ruth] Tel Aviv Univ, Sackler Inst Mol Med, Sackler Sch Med, Dept Human Genet & Mol Med, IL-69978 Tel Aviv, Israel. [Liu, Jin] Univ Texas SW Med Ctr Dallas, Dept Biophys, Dallas, TX 75390 USA. [Liu, Jin] So Methodist Univ, Dept Chem, Ctr Drug Discovery Design & Delivery CD4, Dallas, TX 75275 USA. [Liu, Jin] So Methodist Univ, Ctr Sci Computat, Dallas, TX 75275 USA. RP Nussinov, R (reprint author), NCI, Canc & Inflammat Program, Leidos Biomed Res Inc, Frederick Natl Lab Canc Res, Frederick, MD 21702 USA. EM nussinor@helix.nih.gov FU National Cancer Institute, National Institutes of Health [HHSN261200800001E]; Intramural Research Program of the NIH, National Cancer Institute, Center for Cancer Research FX This project has been funded in whole or in part with federal funds from the National Cancer Institute, National Institutes of Health, under contract no. HHSN261200800001E. This research was supported (in part) by the Intramural Research Program of the NIH, National Cancer Institute, Center for Cancer Research. NR 131 TC 26 Z9 26 U1 3 U2 79 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0002-7863 J9 J AM CHEM SOC JI J. Am. Chem. Soc. PD DEC 24 PY 2014 VL 136 IS 51 BP 17692 EP 17701 DI 10.1021/ja510028c PG 10 WC Chemistry, Multidisciplinary SC Chemistry GA AX8CY UT WOS:000347139200001 PM 25474128 ER PT J AU Zhou, D Zhang, Z He, LM Du, J Zhang, F Sun, CK Zhou, Y Wang, XW Lin, G Song, KM Wu, LG Yang, Q AF Zhou, Di Zhang, Zhen He, Li-Ming Du, Juan Zhang, Fan Sun, Chong-Kui Zhou, Yu Wang, Xiao-Wei Lin, Ge Song, Ke-Ming Wu, Ling-Gang Yang, Qin TI Conversion of Fibroblasts to Neural Cells by p53 Depletion SO CELL REPORTS LA English DT Article ID ADULT HUMAN FIBROBLASTS; STEM-CELLS; DOPAMINERGIC-NEURONS; FUNCTIONAL-NEURONS; DEFINED FACTORS; CANCER; MOUSE; INDUCTION; SUPPRESSION; CROSSROADS AB Conversion from fibroblasts to neurons has recently been successfully induced. However, the underlying mechanisms are poorly understood. Here, we find that depletion of p53 alone converts fibroblasts into all three major neural lineages. The induced neuronal cells express multiple neuron-specific proteins and generate action potentials and transmitter-receptor-mediated currents. Surprisingly, depletion does not affect the well-known tumorigenic p53 target, p21. Instead, knockdown of p53 upregulates neurogenic transcription factors, which in turn boosts fibroblast-neuron conversion. p53 binds the promoter of the neurogenic transcription factor Neurod2 and regulates its expression during fibroblastneuron conversion. Furthermore, our method provides a high efficiency of conversion in late-passage fibroblasts. Genome-wide transcriptional analysis shows that the p53-deficiency-induced neurons exhibit an expression profile different from parental fibroblasts and similar to control-induced neurons. The results may help to understand and improve neural conversion mechanisms to develop robust neuron-replacement therapy strategies. C1 [Zhou, Di; Du, Juan; Zhang, Fan; Sun, Chong-Kui; Zhou, Yu; Wang, Xiao-Wei; Yang, Qin] Washington Univ, Sch Med, Canc Biol Div, St Louis, MO 63108 USA. [Zhang, Zhen; He, Li-Ming; Wu, Ling-Gang] NINDS, Synapt Transmiss Sect, NIH, Bethesda, MD 20892 USA. [Lin, Ge] Cent S Univ, Inst Reprod & Stem Cell Engn, Changsha 410078, Hunan, Peoples R China. [Song, Ke-Ming] Sigma Aldrich Corp, Res Biotechnol Business Unit, St Louis, MO 63103 USA. RP Wu, LG (reprint author), NINDS, Synapt Transmiss Sect, NIH, Bethesda, MD 20892 USA. EM wul@ninds.nih.gov; qyang@wustl.edu FU Natural Science Foundation [81228017]; Science and Technology Support Program [2014SK3243]; Ministry of Science and Technology (863 program) [2011AA020113] FX We thank Andrew Yoo for helpful suggestions and reagents and Buck Rogers and Wilbur Song for proofreading this manuscript. We thank the Genome Technology Access Center in the Department of Genetics at Washington University School of Medicine for help with genomic analysis. This work is supported in part by grants from the Natural Science Foundation (no. 81228017), the Science and Technology Support Program (no. 2014SK3243), and Ministry of Science and Technology (863 program 2011AA020113). NR 27 TC 2 Z9 2 U1 1 U2 8 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 2211-1247 J9 CELL REP JI Cell Reports PD DEC 24 PY 2014 VL 9 IS 6 BP 2034 EP 2042 DI 10.1016/j.celrep.2014.11.040 PG 9 WC Cell Biology SC Cell Biology GA AX3PX UT WOS:000346852400007 PM 25533343 ER PT J AU Killian, JK Miettinen, M Walker, RL Wang, YH Zhu, YJ Waterfall, JJ Noyes, N Retnakumar, P Yang, ZM Smith, WI Killian, MS Lau, CC Pineda, M Walling, J Stevenson, H Smith, C Wang, ZF Lasota, J Kim, SY Boikos, SA Helman, LJ Meltzer, PS AF Killian, J. Keith Miettinen, Markku Walker, Robert L. Wang, Yonghong Zhu, Yuelin Jack Waterfall, Joshua J. Noyes, Natalia Retnakumar, Parvathy Yang, Zhiming Smith, William I., Jr. Killian, M. Scott Lau, C. Christopher Pineda, Marbin Walling, Jennifer Stevenson, Holly Smith, Carly Wang, Zengfeng Lasota, Jerzy Kim, Su Young Boikos, Sosipatros A. Helman, Lee J. Meltzer, Paul S. TI Recurrent epimutation of SDHC in gastrointestinal stromal tumors SO SCIENCE TRANSLATIONAL MEDICINE LA English DT Article ID CARNEY TRIAD; IDH2 MUTATIONS; SUCCINATE; HYPERMETHYLATION; PARAGANGLIOMA; RECEPTOR; INHIBITION; EXPRESSION; PHENOTYPE; HISTONE AB Succinate dehydrogenase (SDH) is a conserved effector of cellular metabolism and energy production, and loss of SDH function is a driver mechanism in several cancers. SDH-deficient gastrointestinal stromal tumors (dSDH GISTs) collectively manifest similar phenotypes, including hypermethylated epigenomic signatures, tendency to occur in pediatric patients, and lack of KIT/PDGFRA mutations. dSDH GISTs often harbor deleterious mutations in SDH subunit genes (SDHA, SDHB, SDHC, and SDHD, termed SDHx), but some are SDHx wild type (WT). To further elucidate mechanisms of SDH deactivation in SDHx-WT GIST, we performed targeted exome sequencing on 59 dSDH GISTs to identify 43 SDHx-mutant and 16 SDHx-WT cases. Genome-wide DNA methylation and expression profiling exposed SDHC promoter-specific CpG island hypermethylation and gene silencing in SDHx-WT dSDH GISTs [ 15 of 16 cases (94%)]. Six of 15 SDHC-epimutant GISTs occurred in the setting of the multitumor syndrome Carney triad. We observed neither SDHB promoter hypermethylation nor large deletions on chromosome 1q in any SDHx-WT cases. Deep genome sequencing of a 130-kbp (kilo-base pair) window around SDHC revealed no recognizable sequence anomalies in SDHC-epimutant tumors. More than 2000 benign and tumor reference tissues, including stem cells and malignancies with a hypermethylator epigenotype, exhibit solely a non-epimutant SDHC promoter. Mosaic constitutional SDHC promoter hypermethylation in blood and saliva from patients with SDHC-epimutant GIST implicates a postzygotic mechanism in the establishment and maintenance of SDHC epimutation. The discovery of SDHC epimutation provides a unifying explanation for the pathogenesis of dSDH GIST, whereby loss of SDH function stems from either SDHx mutation or SDHC epimutation. C1 [Killian, J. Keith; Walker, Robert L.; Wang, Yonghong; Zhu, Yuelin Jack; Waterfall, Joshua J.; Noyes, Natalia; Retnakumar, Parvathy; Lau, C. Christopher; Pineda, Marbin; Walling, Jennifer; Stevenson, Holly; Meltzer, Paul S.] NCI, Genet Branch, NIH, Bethesda, MD 20892 USA. [Miettinen, Markku; Wang, Zengfeng; Lasota, Jerzy] NIH, Pathol Lab, Ctr Canc Res, Bethesda, MD 20892 USA. [Smith, William I., Jr.] Suburban Hosp, Dept Pathol, Bethesda, MD 20814 USA. [Killian, M. Scott] Univ S Dakota, Vermillion, SD 57069 USA. [Smith, Carly] NHLBI, NIH, Bethesda, MD 20892 USA. [Kim, Su Young; Boikos, Sosipatros A.; Helman, Lee J.] NIH, Pediat Oncol Branch, Ctr Canc Res, Bethesda, MD 20892 USA. RP Meltzer, PS (reprint author), NCI, Genet Branch, NIH, Bethesda, MD 20892 USA. EM pmeltzer@mail.nih.gov OI Miettinen, Markku/0000-0002-3282-8107 FU Life Raft Group; Intramural Research Program of NIH, NCI, Center for Cancer Research FX We thank the Life Raft Group and the Intramural Research Program of NIH, NCI, Center for Cancer Research, for funding this study. NR 30 TC 38 Z9 39 U1 1 U2 10 PU AMER ASSOC ADVANCEMENT SCIENCE PI WASHINGTON PA 1200 NEW YORK AVE, NW, WASHINGTON, DC 20005 USA SN 1946-6234 EI 1946-6242 J9 SCI TRANSL MED JI Sci. Transl. Med. PD DEC 24 PY 2014 VL 6 IS 268 AR 268ra177 DI 10.1126/scitranslmed.3009961 PG 9 WC Cell Biology; Medicine, Research & Experimental SC Cell Biology; Research & Experimental Medicine GA AX3MR UT WOS:000346844100003 PM 25540324 ER PT J AU Lu, XH Mattis, VB Wang, N Al-Ramahi, I van den Berg, N Fratantoni, SA Waldvogel, H Greiner, E Osmand, A Elzein, K Xiao, JB Dijkstra, S de Pril, R Vinters, HV Faull, R Signer, E Kwak, S Marugan, JJ Botas, J Fischer, DF Svendsen, CN Munoz-Sanjuan, I Yang, XW AF Lu, Xiao-Hong Mattis, Virginia B. Wang, Nan Al-Ramahi, Ismael van den Berg, Nick Fratantoni, Silvina A. Waldvogel, Henry Greiner, Erin Osmand, Alex Elzein, Karla Xiao, Jingbo Dijkstra, Sipke de Pril, Remko Vinters, Harry V. Faull, Richard Signer, Ethan Kwak, Seung Marugan, Juan J. Botas, Juan Fischer, David F. Svendsen, Clive N. Munoz-Sanjuan, Ignacio Yang, X. William TI Targeting ATM ameliorates mutant Huntingtin toxicity in cell and animal models of Huntington's disease SO SCIENCE TRANSLATIONAL MEDICINE LA English DT Article ID DOUBLE-STRAND BREAKS; DNA-DAMAGE RESPONSE; ATAXIA-TELANGIECTASIA; OXIDATIVE STRESS; WILD-TYPE; MEDIATES NEURODEGENERATION; INDUCED APOPTOSIS; PROTEIN-KINASE; NEURONS; MICE AB Age-related neurodegenerative disorders including Alzheimer's disease and Huntington's disease (HD) consistently show elevated DNA damage, but the relevant molecular pathways in disease pathogenesis remain unclear. One attractive gene is that encoding the ataxia-telangiectasia mutated (ATM) protein, a kinase involved in the DNA damage response, apoptosis, and cellular homeostasis. Loss-of-function mutations in both alleles of ATM cause ataxia-telangiectasia in children, but heterozygous mutation carriers are disease-free. Persistently elevated ATM signaling has been demonstrated in Alzheimer's disease and in mouse models of other neurodegenerative diseases. We show that ATM signaling was consistently elevated in cells derived from HD mice and in brain tissue from HD mice and patients. ATM knockdown protected from toxicities induced by mutant Huntingtin (mHTT) fragments in mammalian cells and in transgenic Drosophila models. By crossing the murine Atm heterozygous null allele onto BACHD mice expressing full-length human mHTT, we show that genetic reduction of Atm gene dosage by one copy ameliorated multiple behavioral deficits and partially improved neuropathology. Small-molecule ATM inhibitors reduced mHTT-induced death of rat striatal neurons and induced pluripotent stem cells derived from HD patients. Our study provides converging genetic and pharmacological evidence that reduction of ATM signaling could ameliorate mHTT toxicity in cellular and animal models of HD, suggesting that ATM may be a useful therapeutic target for HD. C1 [Lu, Xiao-Hong; Wang, Nan; Greiner, Erin; Yang, X. William] Univ Calif Los Angeles, Semel Inst Neurosci & Human Behav, Ctr Neurobehav Genet, Los Angeles, CA 90095 USA. [Lu, Xiao-Hong; Wang, Nan; Greiner, Erin; Yang, X. William] Univ Calif Los Angeles, David Geffen Sch Med, Dept Psychiat & Biobehav Sci, Los Angeles, CA 90095 USA. [Lu, Xiao-Hong; Wang, Nan; Greiner, Erin; Yang, X. William] Univ Calif Los Angeles, Brain Res Inst, Los Angeles, CA 90095 USA. [Mattis, Virginia B.; Svendsen, Clive N.] Cedars Sinai Med Ctr, Board Governors Regenerat Med Inst, Los Angeles, CA 90048 USA. [Al-Ramahi, Ismael; Elzein, Karla; Botas, Juan] Baylor Coll Med, Dept Mol & Human Genet, Houston, TX 77030 USA. [Al-Ramahi, Ismael; Elzein, Karla; Botas, Juan] Texas Childrens Hosp, Jan & Dan Duncan Neurol Res Inst, Houston, TX 77030 USA. [van den Berg, Nick; Fratantoni, Silvina A.; Dijkstra, Sipke; Fischer, David F.] BioFocus, NL-233 CR Leiden, Netherlands. [Waldvogel, Henry; Faull, Richard] Univ Auckland, Dept Anat Radiol, Ctr Brain Res, Fac Med & Hlth Sci, Auckland 1023, New Zealand. [Osmand, Alex] Dept Biochem & Cellular & Mol Biol, Knoxville, TN 37996 USA. [Xiao, Jingbo; Marugan, Juan J.] NIH, Chem Genom Ctr, Natl Ctr Adv Translat Sci, Rockville, MD 20892 USA. [de Pril, Remko] Galapagos, Leiden, Netherlands. [Vinters, Harry V.] Univ Calif Los Angeles, David Geffen Sch Med, Dept Pathol & Lab Med Neurol, Los Angeles, CA 90095 USA. [Signer, Ethan; Kwak, Seung; Munoz-Sanjuan, Ignacio] CHDI Management Inc, CHDI Fdn, Los Angeles, CA 90045 USA. RP Yang, XW (reprint author), Univ Calif Los Angeles, Semel Inst Neurosci & Human Behav, Ctr Neurobehav Genet, Los Angeles, CA 90095 USA. EM xwyang@mednet.ucla.edu RI Al-Ramahi, Ismael/B-4000-2017 OI Al-Ramahi, Ismael/0000-0002-1275-1114 FU National Institute of Neurological Disorders and Stroke (NINDS)/NIH [R01 NS049501, R01 NS074312]; Hereditary Disease Foundation; CHDI Foundation; David Weil Fund; Neuroscience of Brain Disorders Award from The McKnight Foundation; NINDS/NIH [R01 NS074312]; UCLA Alzheimer's Disease Research Center (National Institute on Aging/NIH) [P50 AG16570]; NIH [NS42179] FX X.W.Y. is supported by the National Institute of Neurological Disorders and Stroke (NINDS)/NIH (grants R01 NS049501 and R01 NS074312), the Hereditary Disease Foundation, CHDI Foundation, the David Weil Fund to the Semel Institute at UCLA, and the Neuroscience of Brain Disorders Award from The McKnight Foundation. X.W.Y. is the Carol Moss Spivak Scholar in Neuroscience at the UCLA Brain Research Institute. This work is supported in part by a supplement grant from NINDS/NIH (R01 NS074312). H.V.V. is supported by UCLA Alzheimer's Disease Research Center (National Institute on Aging/NIH P50 AG16570). J.B. is supported by NIH grant NS42179. NR 74 TC 13 Z9 13 U1 1 U2 27 PU AMER ASSOC ADVANCEMENT SCIENCE PI WASHINGTON PA 1200 NEW YORK AVE, NW, WASHINGTON, DC 20005 USA SN 1946-6234 EI 1946-6242 J9 SCI TRANSL MED JI Sci. Transl. Med. PD DEC 24 PY 2014 VL 6 IS 268 AR 268ra178 DI 10.1126/scitranslmed.3010523 PG 12 WC Cell Biology; Medicine, Research & Experimental SC Cell Biology; Research & Experimental Medicine GA AX3MR UT WOS:000346844100004 PM 25540325 ER PT J AU Shankaran, S Laptook, AR Pappas, A McDonald, SA Das, A Tyson, JE Poindexter, BB Schibler, K Bell, EF Heyne, RJ Pedroza, C Bara, R Van Meurs, KP Grisby, C Huitema, CMP Garg, M Ehrenkranz, RA Shepherd, EG Chalak, LF Hamrick, SEG Khan, AM Reynolds, AM Laughon, MM Truog, WE Dysart, KC Carlo, WA Walsh, MC Watterberg, KL Higgins, RD AF Shankaran, Seetha Laptook, Abbot R. Pappas, Athina McDonald, Scott. A. Das, Abhik Tyson, Jon E. Poindexter, Brenda B. Schibler, Kurt Bell, Edward F. Heyne, Roy J. Pedroza, Claudia Bara, Rebecca Van Meurs, Krisa P. Grisby, Cathy Huitema, Carolyn M. Petrie Garg, Meena Ehrenkranz, Richard A. Shepherd, Edward G. Chalak, Lina F. Hamrick, Shannon E. G. Khan, Amir M. Reynolds, Anne Marie Laughon, Matthew M. Truog, William E. Dysart, Kevin C. Carlo, Waldemar A. Walsh, Michele C. Watterberg, Kristi L. Higgins, Rosemary D. CA Eunice Kennedy Shriver Natl Inst C TI Effect of Depth and Duration of Cooling on Deaths in the NICU Among Neonates With Hypoxic Ischemic Encephalopathy A Randomized Clinical Trial SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Article ID WHOLE-BODY HYPOTHERMIA; SYSTEMIC HYPOTHERMIA; CHILDHOOD OUTCOMES; DEEP HYPOTHERMIA; NEUROPROTECTION; TEMPERATURE; ASPHYXIA; INJURY; SAFETY; RISK AB IMPORTANCE Hypothermia at 33.5 degrees C for 72 hours for neonatal hypoxic ischemic encephalopathy reduces death or disability to 44% to 55%; longer cooling and deeper cooling are neuroprotective in animal models. OBJECTIVE To determine if longer duration cooling (120 hours), deeper cooling (32.0 degrees C), or both are superior to cooling at 33.5 degrees C for 72 hours in neonates who are full-term with moderate or severe hypoxic ischemic encephalopathy. DESIGN, SETTING, AND PARTICIPANTS A randomized, 2 x 2 factorial design clinical trial performed in 18 US centers in the Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) Neonatal Research Network between October 2010 and November 2013. INTERVENTIONS Neonates were assigned to 4 hypothermia groups; 33.5 degrees C for 72 hours, 32.0 degrees C for 72 hours, 33.5 degrees C for 120 hours, and 32.0 degrees C for 120 hours. MAIN OUTCOMES AND MEASURES The primary outcome of death or disability at 18 to 22 months is ongoing. The independent data and safety monitoring committee paused the trial to evaluate safety (cardiac arrhythmia, persistent acidosis, major vessel thrombosis and bleeding, and death in the neonatal intensive care unit [NICU]) after the first 50 neonates were enrolled, then after every subsequent 25 neonates. The trial was closed for emerging safety profile and futility analysis after the eighth review with 364 neonates enrolled (of 726 planned). This report focuses on safety and NICU deaths by marginal comparisons of 72 hours' vs 120 hours' duration and 33.5 degrees C depth vs 32.0 degrees C depth (predefined secondary outcomes). RESULTS The NICU death rates were 7 of 95 neonates (7%) for the 33.5 degrees C for 72 hours group, 13 of 90 neonates (14%) for the 32.0 degrees C for 72 hours group, 15 of 96 neonates (16%) for the 33.5 degrees C for 120 hours group, and 14 of 83 neonates (17%) for the 32.0 degrees C for 120 hours group. The adjusted risk ratio (RR) for NICU deaths for the 120 hours group vs 72 hours group was 1.37 (95% CI, 0.92-2.04) and for the 32.0 degrees C group vs 33.5 degrees C group was 1.24 (95% CI, 0.69-2.25). Safety outcomes were similar between the 120 hours group vs 72 hours group and the 32.0 degrees C group vs 33.5 degrees C group, except major bleeding occurred among 1% in the 120 hours group vs 3% in the 72 hours group (RR, 0.25 [95% CI, 0.07-0.91]). Futility analysis determined that the probability of detecting a statistically significant benefit for longer cooling, deeper cooling, or both for NICU death was less than 2%. CONCLUSIONS AND RELEVANCE Among neonates who were full-term with moderate or severe hypoxic ischemic encephalopathy, longer cooling, deeper cooling, or both compared with hypothermia at 33.5 degrees C for 72 hours did not reduce NICU death. These results have implications for patient care and design of future trials. C1 [Shankaran, Seetha; Pappas, Athina; Bara, Rebecca] Wayne State Univ, Dept Pediat, Detroit, MI 48201 USA. [Laptook, Abbot R.] Brown Univ, Women & Infants Hosp, Dept Pediat, Providence, RI 02908 USA. [McDonald, Scott. A.] RTI Int, Social Stat & Environm Sci Unit, Res Triangle Pk, NC USA. [Das, Abhik; Huitema, Carolyn M. Petrie] RTI Int, Social Stat & Environm Sci Unit, Rockville, MD USA. [Tyson, Jon E.; Khan, Amir M.] Univ Texas Houston, Sch Med, Dept Pediat, Houston, TX USA. [Poindexter, Brenda B.] Indiana Univ Sch Med, Dept Pediat, Indianapolis, IN 46202 USA. [Schibler, Kurt; Pedroza, Claudia; Grisby, Cathy] Cincinnati Childrens Hosp Med Ctr, Perinatal Inst, Cincinnati, OH 45229 USA. [Bell, Edward F.] Univ Iowa, Dept Pediat, Iowa City, IA 52242 USA. [Heyne, Roy J.; Chalak, Lina F.] Univ Texas SW Med Ctr Dallas, Dept Pediat, Dallas, TX 75390 USA. [Van Meurs, Krisa P.] Stanford Univ, Sch Med, Div Neonatal & Dev Med, Dept Pediat,Lucile Packard Childrens Hosp, Palo Alto, CA 94304 USA. [Garg, Meena] Univ Calif Los Angeles, Dept Pediat, Los Angeles, CA 90024 USA. [Ehrenkranz, Richard A.] Yale Univ, Sch Med, Dept Pediat, New Haven, CT 06510 USA. [Shepherd, Edward G.] Ohio State Univ, Nationwide Childrens Hosp, Dept Pediat, Columbus, OH 43210 USA. [Hamrick, Shannon E. G.] Emory Univ, Sch Med, Dept Pediat, Childrens Healthcare Atlanta, Atlanta, GA USA. [Reynolds, Anne Marie] SUNY Buffalo, Dept Pediat, Buffalo, NY 14260 USA. [Laughon, Matthew M.] Univ N Carolina, Dept Pediat, Div Neonatal Perinatal Med, Chapel Hill, NC USA. [Truog, William E.] Univ Missouri, Childrens Mercy Hosp, Kansas City Sch Med, Dept Pediat, Columbia, MO 65211 USA. [Dysart, Kevin C.] Univ Penn, Childrens Hosp Philadelphia, Dept Pediat, Perelman Sch Med, Philadelphia, PA 19104 USA. [Carlo, Waldemar A.] Univ Alabama Birmingham, Div Neonatol, Birmingham, AL USA. [Walsh, Michele C.] Case Western Reserve Univ, Rainbow Babies & Childrens Hosp, Dept Pediat, Cleveland, OH 44106 USA. [Watterberg, Kristi L.] Univ New Mexico, Hlth Sci Ctr, Albuquerque, NM 87131 USA. [Higgins, Rosemary D.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Pregnancy & Perinatol Branch, NIH, Bethesda, MD USA. RP Shankaran, S (reprint author), Wayne State Univ, Childrens Hosp Michigan, Dept Pediat, 3901 Beaubien Blvd, Detroit, MI 48201 USA. EM sshankar@med.wayne.edu RI Shah, Birju/C-4811-2014; Shepherd, Edward/E-4080-2011; OI Shah, Birju/0000-0002-9051-1183; Lakshminrusimha, Satyan/0000-0001-6098-2155; Ambalavanan, Namasivayam/0000-0003-0731-9092; Keszler, Martin/0000-0002-9964-664X 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 Neonatal Research Network's Optimizing Cooling trial through cooperative agreements. NR 32 TC 41 Z9 42 U1 1 U2 17 PU AMER MEDICAL ASSOC PI CHICAGO PA 330 N WABASH AVE, STE 39300, CHICAGO, IL 60611-5885 USA SN 0098-7484 EI 1538-3598 J9 JAMA-J AM MED ASSOC JI JAMA-J. Am. Med. Assoc. PD DEC 24 PY 2014 VL 312 IS 24 BP 2629 EP 2639 DI 10.1001/jama.2014.16058 PG 11 WC Medicine, General & Internal SC General & Internal Medicine GA AX5KW UT WOS:000346966100015 PM 25536254 ER PT J AU Sharma, A Berga-Bolanos, R Sen, JM AF Sharma, Archna Berga-Bolanos, Rosa Sen, Jyoti Misra TI T Cell Factor-1 Controls the Lifetime of CD4+CD8+Thymocytes In Vivo and Distal T Cell Receptor alpha-Chain Rearrangement Required for NKT Cell Development SO PLOS ONE LA English DT Article ID THYMOCYTE SURVIVAL; TCRA REARRANGEMENT; LINEAGE; DIFFERENTIATION; SPECIFICATION; PATHWAY; REPERTOIRE; SELECTION; WNT AB Natural killer T (NKT) cells are a component of innate and adaptive immune systems implicated in immune, autoimmune responses and in the control of obesity and cancer. NKT cells develop from common CD4+ CD8+ double positive (DP) thymocyte precursors after the rearrangement and expression of T cell receptor (TCR) V alpha 14-J alpha 18 gene. Temporal regulation and late appearance of V alpha 14-J alpha 18 rearrangement in immature DP thymocytes has been demonstrated. However, the precise control of lifetime of DP thymocytes in vivo that enables distal rearrangements remains incompletely defined. Here we demonstrate that T cell factor (TCF)-1, encoded by the Tcf7 gene, is critical for the extended lifetime of DP thymocytes. TCF-1-deficient DP thymocytes fail to undergo TCR V alpha 14-J alpha 18 rearrangement and produce significantly fewer NKT cells. Ectopic expression of Bcl-x(L) permits V alpha 14-J alpha 18 rearrangement and rescues NKT cell development. We report that TCF-1 regulates expression of ROR gamma t, which regulates DP thymocyte survival by controlling expression of Bcl-x(L). We posit that TCF-1 along with its cofactors controls the lifetime of DP thymocytes in vivo. C1 [Sharma, Archna; Berga-Bolanos, Rosa; Sen, Jyoti Misra] NIA, Immune Cells & Inflammat Sect, NIH, Baltimore, MD 21224 USA. RP Sen, JM (reprint author), NIA, Immune Cells & Inflammat Sect, NIH, Baltimore, MD 21224 USA. EM Jyoti-Sen@nih.gov RI Sharma, Archna/R-9377-2016 OI Sharma, Archna/0000-0003-4745-0220 FU Intramural Research Program of the National Institute on Aging at the NIH FX This research was supported by the Intramural Research Program of the National Institute on Aging at the NIH. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 26 TC 2 Z9 2 U1 0 U2 0 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA SN 1932-6203 J9 PLOS ONE JI PLoS One PD DEC 23 PY 2014 VL 9 IS 12 AR e115803 DI 10.1371/journal.pone.0115803 PG 12 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA AZ9UY UT WOS:000348563300076 PM 25536344 ER PT J AU Redheuil, A Wu, CO Kachenoura, N Ohyama, Y Yan, RT Bertoni, AG Hundley, GW Duprez, DA Jacobs, DR Daniels, LB Darwin, C Sibley, C Bluemke, DA Lima, JAC AF Redheuil, Alban Wu, Colin O. Kachenoura, Nadjia Ohyama, Yoshiaki Yan, Raymond T. Bertoni, Alain G. Hundley, Gregory W. Duprez, Daniel A. Jacobs, David R. Daniels, Lori B. Darwin, Christine Sibley, Christopher Bluemke, David A. Lima, Joao A. C. TI Proximal Aortic Distensibility Is an Independent Predictor of All-Cause Mortality and Incident CV Events The MESA Study SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Article DE aortic stiffness; cardiovascular risk; magnetic resonance imaging; mortality ID CARDIOVASCULAR RISK-FACTORS; LEFT-VENTRICULAR MASS; PULSE-WAVE VELOCITY; ARTERIAL STIFFNESS; ATHEROSCLEROSIS MESA; HYPERTENSIVE PATIENTS; AGE; DETERMINANTS; DYSFUNCTION; THICKNESS AB BACKGROUND The predictive value of ascending aortic distensibility (AAD) for mortality and hard cardiovascular disease (CVD) events has not been fully established. OBJECTIVES This study sought to assess the utility of AAD to predict mortality and incident CVD events beyond conventional risk factors in MESA (Multi-Ethnic Study of Atherosclerosis). METHODS AAD was measured with magnetic resonance imaging at baseline in 3,675 MESA participants free of overt CVD. Cox proportional hazards regression was used to evaluate risk of death, heart failure (HF), and incident CVD in relation to AAD, CVD risk factors, indexes of subclinical atherosclerosis, and Framingham risk score. RESULTS There were 246 deaths, 171 hard CVD events (myocardial infarction, resuscitated cardiac arrest, stroke and CV death), and 88 HF events over a median 8.5-year follow-up. Decreased AAD was associated with increased all-cause mortality with a hazard ratio (HR) for the first versus fifth quintile of AAD of 2.7 (p = 0.008) independent of age, sex, ethnicity, other CVD risk factors, and indexes of subclinical atherosclerosis. Overall, patients with the lowest AAD had an independent 2-fold higher risk of hard CVD events. Decreased AAD was associated with CV events in low to intermediate-CVD risk individuals with an HR for the first quintile of AAD of 5.3 (p = 0.03) as well as with incident HF but not after full adjustment. CONCLUSIONS Decreased proximal aorta distensibility significantly predicted all-cause mortality and hard CV events among individuals without overt CVD. AAD may help refine risk stratification, especially among asymptomatic, low-to intermediate-risk individuals. (C) 2014 by the American College of Cardiology Foundation. C1 [Redheuil, Alban; Kachenoura, Nadjia] UPMC, Univ Sorbonne, INSERM, Lab Imagerie Biomed,UMR S1146, Paris, France. [Redheuil, Alban] La Pitie Salpetriere, Cardiovasc Imaging Dept, Paris, France. [Redheuil, Alban] Hop La Pitie Salpetriere, ICAN Imaging Core Lab, Paris, France. [Wu, Colin O.] NHLBI, Off Biostat Res, Bethesda, MD 20892 USA. [Ohyama, Yoshiaki; Lima, Joao A. C.] Johns Hopkins Univ, Div Cardiol & Radiol, Baltimore, MD USA. [Yan, Raymond T.] Univ Toronto, Dept Med, Toronto, ON, Canada. [Bertoni, Alain G.; Hundley, Gregory W.] Wake Forest Sch Med, Dept Epidemiol & Prevent, Winston Salem, NC USA. [Duprez, Daniel A.; Jacobs, David R.] Univ Minnesota, Sch Publ Hlth, Div Cardiol, Minneapolis, MN USA. [Daniels, Lori B.] Univ Minnesota, Sch Publ Hlth, Div Epidemiol & Community Hlth, Minneapolis, MN USA. [Darwin, Christine] Univ Calif San Diego, Div Cardiol, La Jolla, CA 92093 USA. [Bluemke, David A.; Lima, Joao A. C.] Univ Calif Los Angeles, Res Ctr, Alhambra, CA USA. [Bluemke, David A.; Lima, Joao A. C.] NIH, Bethesda, MD 20892 USA. RP Redheuil, A (reprint author), UPMC, Univ Sorbonne, INSERM, Lab Imagerie Biomed,UMR S1146, Paris, France. OI Bluemke, David/0000-0002-8323-8086 FU National Heart, Lung, and Blood Institute [N01-HC-95159, N01-HC-95169]; Sanofi; Regeneron; Pfizer FX MESA was supported by contracts N01-HC-95159 through N01-HC-95169 from the National Heart, Lung, and Blood Institute. Dr. Duprez has received research grants from Sanofi, Regeneron, and Pfizer; and served on advisory boards for AstraZeneca and Novartis. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose. NR 29 TC 18 Z9 18 U1 2 U2 5 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0735-1097 EI 1558-3597 J9 J AM COLL CARDIOL JI J. Am. Coll. Cardiol. PD DEC 23 PY 2014 VL 64 IS 24 BP 2619 EP 2629 DI 10.1016/j.jacc.2014.09.060 PG 11 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA AW5ZL UT WOS:000346349300010 PM 25524341 ER PT J AU Kashi, VP Jacob, RA Shamanna, RA Menon, M Balasiddaiah, A Varghese, RK Bachu, M Ranga, U AF Kashi, Venkatesh P. Jacob, Rajesh A. Shamanna, Raghavendra A. Menon, Malini Balasiddaiah, Anangi Varghese, Rebu K. Bachu, Mahesh Ranga, Udaykumar TI The Grafting of Universal T-Helper Epitopes Enhances Immunogenicity of HIV-1 Tat Concurrently Improving Its Safety Profile SO PLoS One LA English DT Article ID HUMAN-IMMUNODEFICIENCY-VIRUS; CLADE-SPECIFIC DIFFERENCES; IMMUNE-RESPONSES; TYPE-1 TAT; NEUTRALIZING ANTIBODIES; CYNOMOLGUS MONKEYS; RHESUS MACAQUES; 89.6P CHALLENGE; PROTEIN; AIDS AB Extracellular Tat (eTat) plays an important role in HIV-1 pathogenesis. The presence of anti-Tat antibodies is negatively correlated with disease progression, hence making Tat a potential vaccine candidate. The cytotoxicity and moderate immunogenicity of Tat however remain impediments for developing Tat-based vaccines. Here, we report a novel strategy to concurrently enhance the immunogenicity and safety profile of Tat. The grafting of universal helper T-lymphocyte (HTL) epitopes, Pan DR Epitope (PADRE) and Pol(711) into the cysteine rich domain (CRD) and the basic domain (BD) abolished the transactivation potential of the Tat protein. The HTL-Tat proteins elicited a significantly higher titer of antibodies as compared to the wild-type Tat in BALB/c mice. While the N-terminal epitope remained immunodominant in HTL-Tat immunizations, an additional epitope in exon-2 was recognized with comparable magnitude suggesting a broader immune recognition. Additionally, the HTL-Tat proteins induced cross-reactive antibodies of high avidity that efficiently neutralized exogenous Tat, thus blocking the activation of a Tat-defective provirus. With advantages such as presentation of multiple B-cell epitopes, enhanced antibody response and importantly, transactivation-deficient Tat protein, this approach has potential application for the generation of Tat-based HIV/AIDS vaccines. C1 [Kashi, Venkatesh P.; Jacob, Rajesh A.; Shamanna, Raghavendra A.; Menon, Malini; Balasiddaiah, Anangi; Varghese, Rebu K.; Bachu, Mahesh; Ranga, Udaykumar] Jawaharlal Nehru Ctr Adv Sci Res, HIV AIDS Lab, Mol Biol & Genet Unit, Bangalore 560064, Karnataka, India. [Jacob, Rajesh A.] Int Ctr Genet Engn & Biotechnol, Cellular Immunol Grp, Cape Town, South Africa. [Shamanna, Raghavendra A.] NIA, Lab Mol Gerontol, Baltimore, MD 21224 USA. RP Ranga, U (reprint author), Jawaharlal Nehru Ctr Adv Sci Res, HIV AIDS Lab, Mol Biol & Genet Unit, Bangalore 560064, Karnataka, India. EM udaykumar@jncasr.ac.in FU Indian Council of Medical Research, India [HIV/50/114/09-ECDII, 2008-06300]; Jawaharlal Nehru Center for Advanced Scientific Research to Udaykumar Ranga FX This study was supported by grants from the Indian Council of Medical Research, India (HIV/50/114/09-ECDII, IRIS No. 2008-06300) and intramural grants from Jawaharlal Nehru Center for Advanced Scientific Research to Udaykumar Ranga. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 46 TC 2 Z9 2 U1 1 U2 7 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA SN 1932-6203 J9 PLOS ONE JI PLoS One PD DEC 22 PY 2014 VL 9 IS 12 AR e114155 DI 10.1371/journal.pone.0114155 PG 17 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA CA3ZY UT WOS:000348845100009 PM 25531437 ER PT J AU Kumar, S Zheng, H Deng, BB Mahajan, B Grabias, B Kozakai, Y Morin, MJ Locke, E Birkett, A Miura, K Long, C AF Kumar, Sanjai Zheng, Hong Deng, Bingbing Mahajan, Babita Grabias, Bryan Kozakai, Yukiko Morin, Merribeth J. Locke, Emily Birkett, Ashley Miura, Kazutoyo Long, Carole TI A Slot Blot Immunoassay for Quantitative Detection of Plasmodium falciparum Circumsporozoite Protein in Mosquito Midgut Oocyst SO PLoS One LA English DT Article ID LINKED-IMMUNOSORBENT-ASSAY; MALARIA TRANSMISSION; FALSE POSITIVITY; SPOROZOITES; VIVAX; ANTIBODIES; PFS48/45; ANTIGEN; VACCINE; VECTOR AB There is still a need for sensitive and reproducible immunoassays for quantitative detection of malarial antigens in preclinical and clinical phases of vaccine development and in epidemiology and surveillance studies, particularly in the vector host. Here we report the results of sensitivity and reproducibility studies for a research-grade, quantitative enhanced chemiluminescent-based slot blot assay (ECL-SB) for detection of both recombinant Plasmodium falciparum circumsporozoite protein (rPfCSP) and native PfCSP from Oocysts (Pf Oocyst) developing in the midguts of Anopheles stephensi mosquitoes. The ECL-SB detects as little as 1.25 pg of rPfCSP (linear range of quantitation 2.5-20 pg; R-2 = 0.9505). We also find the earliest detectable expression of native PfCSP in Pf Oocyst by ECL-SB occurs on day 7 post feeding with infected blood meal. The ECL-SB was able to detect approximately as few as 0.5 day 8 Pf Oocysts (linear quantitation range 1-4, R-2 = 0.9795) and determined that one Pf Oocyst expressed approximately 2.0 pg (0.5-3 pg) of native PfCSP, suggesting a similar range of detection for recombinant and native forms of PfCSP. The ECL-SB is highly reproducible; the Coefficient of Variation (CV) for inter-assay variability for rPfCSP and native PfCSP were 1.74% and 1.32%, respectively. The CVs for intra-assay variability performed on three days for rPfCSP were 2.41%, 0.82% and 2% and for native PfCSP 1.52%, 0.57%, and 1.86%, respectively. In addition, the ECL-SB was comparable to microscopy in determining the P. falciparum prevalence in mosquito populations that distinctly contained either high and low midgut Pf Oocyst burden. In whole mosquito samples, estimations of positivity for P. falciparum in the high and low burden groups were 83.3% and 23.3% by ECL-SB and 85.7% and 27.6% by microscopy. Based on its performance characteristics, ECL-SB could be valuable in vaccine development and to measure the parasite prevalence in mosquitoes and transmission-blocking interventions in endemic areas. C1 [Kumar, Sanjai; Zheng, Hong; Mahajan, Babita; Grabias, Bryan; Kozakai, Yukiko] Ctr Biol Evaluat & Res Food & Drug Adm, Div Emerging & Transfus Transmitted Dis, Lab Emerging Pathogens, Silver Spring, MD 20993 USA. [Deng, Bingbing; Miura, Kazutoyo; Long, Carole] NIAID, Lab Malaria & Vector Res, NIH, Rockville, MD 20852 USA. [Morin, Merribeth J.; Locke, Emily; Birkett, Ashley] PATH Malaria Vaccine Initiat, Washington, DC 20001 USA. RP Kumar, S (reprint author), Ctr Biol Evaluat & Res Food & Drug Adm, Div Emerging & Transfus Transmitted Dis, Lab Emerging Pathogens, Silver Spring, MD 20993 USA. EM Sanjai.kumar@fda.hhs.gov FU PATH Malaria Vaccine Initiative; US Food and Drug Administration [CRADA 145-08]; National Institute of Allergy and Infectious Diseases FX This research was funded, in part, through financial support from the PATH Malaria Vaccine Initiative (http://www.malariavaccine.org, SK) and intramural funding from the US Food and Drug Administration (http://www.FDA.gov, SK, CRADA 145-08) and the National Institute of Allergy and Infectious Diseases (http://www.NIAID.NIH.gov, CL). The Path Malaria Vaccine initiative was extensively involved in the design of the study, data collection and analysis, decision to publish, and the preparation of the manuscript. All other funders had no such involvement. NR 25 TC 2 Z9 2 U1 0 U2 1 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA SN 1932-6203 J9 PLOS ONE JI PLoS One PD DEC 22 PY 2014 VL 9 IS 12 AR e115807 DI 10.1371/journal.pone.0115807 PG 20 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA CA3ZY UT WOS:000348845100110 PM 25531543 ER PT J AU Kuranov, AB Vavilov, MN Abildinova, GZ Akilzhanova, AR Iskakova, AN Zholdybayeva, EV Boldyreva, MN Muller, CA Momynaliev, KT AF Kuranov, Alexandr B. Vavilov, Mikhail N. Abildinova, Gulshara Zh. Akilzhanova, Ainur R. Iskakova, Aisha N. Zholdybayeva, Elena V. Boldyreva, Margarita N. Mueller, Claudia A. Momynaliev, Kuvat T. TI Polymorphisms of HLA-DRB1,-DQA1 and-DQB1 in Inhabitants of Astana, the Capital City of Kazakhstan SO PLoS One LA English DT Article ID CLASS-II ALLELE; HLA CLASS-I; SIBERIAN POPULATIONS; HAPLOTYPE FREQUENCIES; MOLECULAR ANALYSIS; GENE-FREQUENCIES; ETHNIC-GROUPS; RUSSIA; ORIGIN; DIVERSITY AB Background: Kazakhstan has been inhabited by different populations, such as the Kazakh, Kyrgyz, Uzbek and others. Here we investigate allelic and haplotypic polymorphisms of human leukocyte antigen (HLA) genes at DRB1, DQA1 and DQB1 loci in the Kazakh ethnic group, and their genetic relationship between world populations. Methodology/Principal Findings: A total of 157 unrelated Kazakh ethnic individuals from Astana were genotyped using sequence based typing (SBTMethod) for HLA-DRB1, -DQA1 and -DQB1 loci. Allele frequencies, neighborjoining method, and multidimensional scaling analysis have been obtained for comparison with other world populations. Statistical analyses were performed using Arlequin v3.11. Applying the software PAST v. 2.17 the resulting genetic distance matrix was used for a multidimensional scaling analysis (MDS). Respectively 37, 17 and 19 alleles were observed at HLA-DRB1, -DQA1 and -DQB1 loci. The most frequent alleles were HLA-DRB1*07: 01 (13.1%), HLA-DQA1*03:01 (13.1%) and HLA-DQB1*03:01 (17.6%). In the observed group of Kazakhs DRB1*07:01DQA1* 02: 01-DQB1*02: 01 (8.0%) was the most common three loci haplotype. DRB1*10:01-DQB1*05:01 showed the strongest linkage disequilibrium. The Kazakh population shows genetic kinship with the Kazakhs from China, Uyghurs, Mongolians, Todzhinians, Tuvinians and as well as with other Siberians and Asians. Conclusions/Significance: The HLA-DRB1, -DQA1and -DQB1 loci are highly polymorphic in the Kazakh population, and this population has the closest relationship with other Asian and Siberian populations. C1 [Kuranov, Alexandr B.; Mueller, Claudia A.] Med Univ Clin, Tubingen, Germany. [Vavilov, Mikhail N.] Chelyabinsk Reg Blood Ctr, Chelyabinsk, Russia. [Abildinova, Gulshara Zh.] Natl Res Ctr Maternal & Child Hlth, Astana, Kazakhstan. [Akilzhanova, Ainur R.; Iskakova, Aisha N.; Zholdybayeva, Elena V.; Momynaliev, Kuvat T.] Natl Biotechnol Ctr, Astana, Kazakhstan. [Boldyreva, Margarita N.] NRC Inst Immunol FMBA Russia, Moscow, Russia. RP Kuranov, AB (reprint author), Med Univ Clin, Tubingen, Germany. EM iskander.kuranov@gmail.com RI Iskakova, Aisha/C-7136-2015 OI Iskakova, Aisha/0000-0002-0631-062X FU Ministry of Education and Science of the Republic of Kazakhstan [N01.04.01]; German Academic Exchange Service (DAAD); Deutsche Forschungsgemeinschaft and Open Access Publishing Fund of Tubingen University FX This research was supported by funding from the Ministry of Education and Science of the Republic of Kazakhstan N01.04.01, German Academic Exchange Service (DAAD) for Alexandr B. Kuranov, Deutsche Forschungsgemeinschaft and Open Access Publishing Fund of Tubingen University. This work was also supported in part by an intramural funding. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 72 TC 1 Z9 1 U1 1 U2 7 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA SN 1932-6203 J9 PLOS ONE JI PLoS One PD DEC 22 PY 2014 VL 9 IS 12 AR e115265 DI 10.1371/journal.pone.0115265 PG 18 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA CA3ZY UT WOS:000348845100047 PM 25531278 ER PT J AU Clough, E Jimenez, E Kim, YA Whitworth, C Neville, MC Hempel, LU Pavlou, HJ Chen, ZX Sturgill, D Dale, RK Smith, HE Przytycka, TM Goodwin, SF Van Doren, M Oliver, B AF Clough, Emily Jimenez, Erin Kim, Yoo-Ah Whitworth, Cale Neville, Megan C. Hempel, Leonie U. Pavlou, Hania J. Chen, Zhen-Xia Sturgill, David Dale, Ryan K. Smith, Harold E. Przytycka, Teresa M. Goodwin, Stephen F. Van Doren, Mark Oliver, Brian TI Sex- and Tissue-Specific Functions of Drosophila Doublesex Transcription Factor Target Genes SO DEVELOPMENTAL CELL LA English DT Article ID GENITAL IMAGINAL DISC; DNA-SEQUENCES; RNA-SEQ; EXPRESSION ANALYSIS; H3K79 METHYLATION; JUVENILE-HORMONE; NERVOUS-SYSTEM; DM DOMAIN; MELANOGASTER; EVOLUTION AB Primary sex-determination "switches" evolve rapidly, but Doublesex (DSX)-related transcription factors (DMRTs) act downstream of these switches to control sexual development in most animal species. Drosophila dsx encodes female- and male-specific isoforms (DSXF and DSXM), but little is known about how dsx controls sexual development, whether DSXF and DSXM bind different targets, or how DSX proteins direct different outcomes in diverse tissues. We undertook genome-wide analyses to identify DSX targets using in vivo occupancy, binding site prediction, and evolutionary conservation. We find that DSXF and DSXM bind thousands of the same targets in multiple tissues in both sexes, yet these targets have sex- and tissue-specific functions. Interestingly, DSX targets show considerable overlap with targets identified for mouse DMRT1. DSX targets include transcription factors and signaling pathway components providing for direct and indirect regulation of sex- biased expression. C1 [Clough, Emily; Whitworth, Cale; Hempel, Leonie U.; Chen, Zhen-Xia; Sturgill, David; Dale, Ryan K.; Smith, Harold E.; Oliver, Brian] NIDDK, NIH, Bethesda, MD 20892 USA. [Jimenez, Erin; Whitworth, Cale; Van Doren, Mark] Johns Hopkins Univ, Dept Biol, Baltimore, MD 21218 USA. [Kim, Yoo-Ah; Przytycka, Teresa M.] NIH, Computat Biol Branch, NCBI, NLM, Bethesda, MD 20814 USA. [Neville, Megan C.; Pavlou, Hania J.; Goodwin, Stephen F.] Univ Oxford, Dept Physiol Anat & Genet, Oxford OX1 3PT, England. RP Whitworth, C (reprint author), NIDDK, NIH, Bethesda, MD 20892 USA. EM cale.whitworth@nih.gov FU Intramural Research Program of the NIH; National Institute of Diabetes and Digestive and Kidney Diseases; National Center for Biotechnology Information; NIH [5R21HD066244-02, 5F31HD076558-02]; Wellcome Trust [WT085521MA, WT082987MF] FX We thank the Developmental Studies Hybridoma Bank, Drosophila RNAi Screening Center, Bruce Baker, Ken Howard, Gyunghee Lee, Ruth Lehmann, Tony Southall, and Phil Garrett-Engele for stocks and reagents and Shaad Ahmad for comments on the manuscript. This work was supported by the Intramural Research Program of the NIH, the National Institute of Diabetes and Digestive and Kidney Diseases (B.O.), and the National Center for Biotechnology Information (T.P.). C.W. and E.J. were supported by NIH grant 5R21HD066244-02 awarded to M.V.D., and E.J. was supported by NIH grant 5F31HD076558-02. M.C.N. and H.J.P. were supported by grants from the Wellcome Trust to S.F.G. (WT085521MA and WT082987MF). This study utilized the high-performance computational capabilities of the Biowulf Linux cluster at the NIH, Bethesda, MD (http://biowulf.nih.gov). Stocks obtained from the Bloomington Drosophila Stock Center (NIH P40OD018537) were used in this study. NR 78 TC 18 Z9 18 U1 4 U2 31 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 22 PY 2014 VL 31 IS 6 BP 761 EP 773 DI 10.1016/j.devcel.2014.11.021 PG 13 WC Cell Biology; Developmental Biology SC Cell Biology; Developmental Biology GA AX1ZL UT WOS:000346742900011 PM 25535918 ER PT J AU Parker, JL Mindell, JA Newstead, S AF Parker, Joanne L. Mindell, Joseph A. Newstead, Simon TI Thermodynamic evidence for a dual transport mechanism in a POT peptide transporter SO ELIFE LA English DT Article ID COUPLED OLIGOPEPTIDE TRANSPORTER; STRUCTURAL BASIS; FAMILY SLC15; PROTON; IDENTIFICATION; STOICHIOMETRY; HPEPT1; COTRANSPORTER; RECOGNITION; BACTERIA AB Peptide transport plays an important role in cellular homeostasis as a key route for nitrogen acquisition in mammalian cells. PepT1 and PepT2, the mammalian proton coupled peptide transporters (POTs), function to assimilate and retain diet-derived peptides and play important roles in drug pharmacokinetics. A key characteristic of the POT family is the mechanism of peptide selectivity, with members able to recognise and transport >8000 different peptides. In this study, we present thermodynamic evidence that in the bacterial POT family transporter PepT(St), from Streptococcus thermophilus, at least two alternative transport mechanisms operate to move peptides into the cell. Whilst tri-peptides are transported with a proton:peptide stoichiometry of 3:1, di-peptides are co-transported with either 4 or 5 protons. This is the first thermodynamic study of proton: peptide stoichiometry in the POT family and reveals that secondary active transporters can evolve different coupling mechanisms to accommodate and transport chemically and physically diverse ligands across the membrane. C1 [Parker, Joanne L.; Newstead, Simon] Univ Oxford, Dept Biochem, Oxford OX1 3QU, England. [Mindell, Joseph A.] NINDS, Membrane Transport Biophys Unit, NIH, Bethesda, MD 20892 USA. RP Newstead, S (reprint author), Univ Oxford, Dept Biochem, Oxford OX1 3QU, England. EM simon.newstead@bioch.ox.ac.uk OI Newstead, Simon/0000-0001-7432-2270 FU Wellcome Trust [102890/Z/13/Z] FX Wellcome Trust 102890/Z/13/Z Simon Newstead NR 36 TC 8 Z9 8 U1 5 U2 13 PU ELIFE SCIENCES PUBLICATIONS LTD PI CAMBRIDGE PA SHERATON HOUSE, CASTLE PARK, CAMBRIDGE, CB3 0AX, ENGLAND SN 2050-084X J9 ELIFE JI eLife PD DEC 22 PY 2014 VL 3 AR e04273 DI 10.7554/eLife.04273 PG 13 WC Biology SC Life Sciences & Biomedicine - Other Topics GA AX2JY UT WOS:000346770700004 ER PT J AU Wang, L Kantovitz, KR Cullinane, AR Nociti, FH Foster, BL Roney, JC Tran, AB Introne, WJ Somerman, MJ AF Wang, Le Kantovitz, Kamila Rosamilia Cullinane, Andrew Robert Nociti, Francisco Humberto, Jr. Foster, Brian Lee Roney, Joseph Concepcion Anne Bich Tran Introne, Wendy Jewell Somerman, Martha Joan TI Skin fibroblasts from individuals with Chediak-Higashi Syndrome (CHS) exhibit hyposensitive immunogenic response SO ORPHANET JOURNAL OF RARE DISEASES LA English DT Article DE Lysosome trafficking regulator; Intracellular vesicle trafficking; Immunodeficiency; Toll-like receptors ID TOLL-LIKE RECEPTORS; CELL; DEFICIENCY; NEUTROPHILS; MICE; TLR4; IDENTIFICATION; ACTIVATION; EXPRESSION; TOLERANCE AB Background: Chediak-Higashi Syndrome (CHS) is a rare autosomal recessive disease characterized by immunodeficiency, oculocutaneous albinism, neurological dysfunction, and early death. Individuals with CHS present with increased susceptibility to infections of the skin, upper-respiratory tract, gastrointestinal tract, and oral tissues. Classical CHS is caused by mutations in the gene encoding lysosomal trafficking regulator (LYST). Although defects in cytotoxic T cell lytic secretory granule secretion and neutrophil phagocytosis are suggested to contribute to the immunodeficiency in CHS, the underlying molecular mechanisms are unknown. We hypothesized that skin fibroblasts from CHS subjects exhibit impaired immune response due to defective trafficking of inflammatory factors. Methods and results: Primary skin fibroblasts from CHS subjects or healthy controls were assessed for genes encoding inflammatory response factors using PCR array. At baseline, we found CD14, IL1R1 and TLR-1 were down-regulated significantly (>= 2 fold change) and the genes encoding TLR-3, IL-1 beta and IL-6 were up-regulated in CHS cells compared to control cells. When challenged with E. coli lipopolysaccharide (LPS), CHS cells were less responsive than control cells, with only 8 genes significantly up-regulated (3-68 fold change) compared to baseline values, whereas 28 genes in control cells were significantly up-regulated at a much higher magnitude (3-4,629 fold change). In addition, 50% of the genes significantly up-regulated in LPS-treated control cells were significantly lower in LPS-treated CHS cells. IL-6, a fibroblast-derived proinflammatory cytokine essential for fighting infections was significantly lower in culture media of CHS cells with or without LPS. Furthermore, Western blot and immunofluorescent staining revealed that TLR-2 and TLR-4 were diminished on cell membranes of CHS cells and dissociated from Rab11a. Conclusions: For the first time, results from our study indicate defective trafficking of TLR-2 and TLR-4 contributes to the hyposensitive response of CHS skin fibroblasts to immunogenic challenge, providing a potential therapeutic target for clinical intervention in CHS. C1 [Wang, Le; Kantovitz, Kamila Rosamilia; Nociti, Francisco Humberto, Jr.; Foster, Brian Lee; Anne Bich Tran; Somerman, Martha Joan] NIAMS Natl Inst Arthrit & Musculoskeletal & Skin, NIH, Bethesda, MD 20892 USA. [Kantovitz, Kamila Rosamilia; Nociti, Francisco Humberto, Jr.] Univ Estadual Campinas, Piracicaba Dent Sch, Sao Paulo, Brazil. [Cullinane, Andrew Robert; Roney, Joseph Concepcion; Introne, Wendy Jewell] NHGRI, NIH, Bethesda, MD 20892 USA. RP Wang, L (reprint author), NIAMS Natl Inst Arthrit & Musculoskeletal & Skin, NIH, Bethesda, MD 20892 USA. EM le.wang@nih.gov RI Nociti, Francisco/G-4907-2015; Foster, Brian/H-8375-2015; Kantovitz, Kamila/J-4567-2013 OI Foster, Brian/0000-0003-3444-0576; Kantovitz, Kamila/0000-0003-2045-7924 FU Intramural Research Program of NIAMS; NHGRI of the NIH FX This research was supported by the Intramural Research Program of NIAMS (LW, KRK, FHN, BLF, ABT, MJS) and NHGRI (ARC, JCR and WJI) of the NIH. The authors acknowledge Dr. Samuel Black (University of Massachusetts at Amherst), Dr. Richard Darveau (University of Washington), and Dr. Vivek Thumbigere-Math (NIAMS/NIH, Bethesda, MD) for scientific advice, and Mudita Patel (NIAMS/NIH, Bethesda, MD) for technique assistance. NR 46 TC 2 Z9 2 U1 0 U2 4 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1750-1172 J9 ORPHANET J RARE DIS JI Orphanet J. Rare Dis. PD DEC 21 PY 2014 VL 9 AR 212 DI 10.1186/s13023-014-0212-7 PG 11 WC Genetics & Heredity; Medicine, Research & Experimental SC Genetics & Heredity; Research & Experimental Medicine GA CC6FL UT WOS:000350460300002 PM 25528552 ER PT J AU Alves, MC Santos, WS Lee, C Bolch, WE Hunt, JG Carvalho, AB AF Alves, M. C. Santos, W. S. Lee, Choonsik Bolch, Wesley E. Hunt, John G. Carvalho Junior, A. B. TI Organ and effective dose conversion coefficients for a sitting female hybrid computational phantom exposed to monoenergetic protons in idealized irradiation geometries SO PHYSICS IN MEDICINE AND BIOLOGY LA English DT Article DE protons; computational dosimetry; conversion coefficients AB The conversion coefficients (CCs) relate protection quantities, mean absorbed dose (D-T) and effective dose (E), with physical radiation field quantities, such as fluence (Phi). The calculation of CCs through Monte Carlo simulations is useful for estimating the dose in individuals exposed to radiation. The aim of this work was the calculation of conversion coefficients for absorbed and effective doses per fluence (D-T/Phi and E/Phi) using a sitting and standing female hybrid phantom (UFH/NCI) exposure to monoenergetic protons with energy ranging from 2 MeV to 10 GeV. The radiation transport code MCNPX was used to develop exposure scenarios implementing the female UFH/NCI phantom in sitting and standing postures. Whole-body irradiations were performed using the recommended irradiation geometries by ICRP publication 116 (AP, PA, RLAT, LLAT, ROT and ISO). In most organs, the conversion coefficients D-T/Phi were similar for both postures. However, relative differences were significant for organs located in the abdominal region, such as ovaries, uterus and urinary bladder, especially in the AP, RLAT and LLAT geometries. Anatomical differences caused by changing the posture of the female UFH/NCI phantom led an attenuation of incident protons with energies below 150 MeV by the thigh of the phantom in the sitting posture, for the front-to-back irradiation, and by the arms and hands of the phantom in the standing posture, for the lateral irradiation. C1 [Alves, M. C.; Carvalho Junior, A. B.] Univ Fed Sergipe, Dept Fis, BR-49100000 Sao Cristovao, SE, Brazil. [Santos, W. S.] Comissao Nacl Energia Nucl IPEN CNEN SP Sao Paulo, Inst Pesquisas Energet & Nucl, Sao Paulo, Brazil. [Lee, Choonsik] NCI, Div Canc Epidemiol & Genet, NIH, Rockville, MD 20852 USA. [Bolch, Wesley E.] Univ Florida, Dept Nucl & Radiol Engn, Gainesville, FL 32611 USA. [Hunt, John G.] Inst Radioprotecao & Dosimetria, Dosimetry Div, BR-22783127 Rio De Janeiro, RJ, Brazil. RP Alves, MC (reprint author), Univ Fed Sergipe, Dept Fis, Campus Prof Jose Aloisio Campos, BR-49100000 Sao Cristovao, SE, Brazil. EM alves.materia@gmail.com NR 15 TC 2 Z9 2 U1 0 U2 2 PU IOP PUBLISHING LTD PI BRISTOL PA TEMPLE CIRCUS, TEMPLE WAY, BRISTOL BS1 6BE, ENGLAND SN 0031-9155 EI 1361-6560 J9 PHYS MED BIOL JI Phys. Med. Biol. PD DEC 21 PY 2014 VL 59 IS 24 BP 7957 EP 8003 DI 10.1088/0031-9155/59/24/7957 PG 47 WC Engineering, Biomedical; Radiology, Nuclear Medicine & Medical Imaging SC Engineering; Radiology, Nuclear Medicine & Medical Imaging GA V41QB UT WOS:000209559600026 PM 25427139 ER PT J AU Arajo-Santos, T Prates, DB Frana-Costa, J Luz, NF Andrade, BB Miranda, JC Brodskyn, CI Barral, A Bozza, PT Borges, VM AF Arajo-Santos, Tho Prates, Deboraci Brito Frana-Costa, Jaqueline Luz, Nvea F. Andrade, Bruno B. Miranda, Jos Carlos Brodskyn, Claudia I. Barral, Aldina Bozza, Patrcia T. Borges, Valria Matos TI Prostaglandin E-2/Leukotriene B-4 balance induced by Lutzomyia longipalpis saliva favors Leishmania infantum infection SO PARASITES & VECTORS LA English DT Article DE Lutzomyia longipalpis; Leishmania infantum; Saliva; Prostaglandina E-2; Leukotriene B-4 ID SAND FLY SALIVA; CUTANEOUS LEISHMANIASIS; AMAZONENSIS INFECTION; EARLY VISCERALIZATION; MOUSE MACROPHAGES; PARASITE BURDEN; LEUKOTRIENES; NEUTROPHILS; INFLAMMATION; MEDIATORS AB Background: Eicosanoids and sand fly saliva have a critical role in the Leishmania infection. Here, we evaluated the effect of Lutzomyia longipalpis salivary gland sonicate (SGS) on neutrophil and monocyte recruitment and activation of eicosanoid production in a murine model of inflammation. Methods: C57BL/6 mice were inoculated intraperitonealy with Lutzomyia longipalpis SGS or Leishmania infantum or both, followed by analyses of cell recruitment, parasite load and eicosanoid production. Results: Intraperitoneal injection of Lutzomyia longipalpis SGS together with Leishmania infantum induced an early increased parasite viability in monocytes and neutrophils. L. longipalpis SGS increased prostaglandin E-2 (PGE(2)), but reduced leukotriene B-4 (LTB4) production ex vivo in peritoneal leukocytes. In addition, the pharmacological inhibition of cyclooxygenase 2 (COX-2) with NS-398 decreased parasite viability inside macrophages during Leishmania infection in the presence of L. longipalpis SGS arguing that PGE(2) production is associated with diminished parasite killing. Conclusions: These findings indicate that L. longipalpis SGS is a critical factor driving immune evasion of Leishmania through modulation of PGE(2)/LTB4 axis, which may represent an important mechanism on establishment of the infection. C1 [Arajo-Santos, Tho; Prates, Deboraci Brito; Frana-Costa, Jaqueline; Luz, Nvea F.; Miranda, Jos Carlos; Brodskyn, Claudia I.; Barral, Aldina; Borges, Valria Matos] Oswaldo Cruz Fdn FIOCRUZ, Gonalo Moniz Res Ctr, Salvador, BA, Brazil. [Frana-Costa, Jaqueline; Luz, Nvea F.; Brodskyn, Claudia I.; Barral, Aldina] Fed Univ Bahia UFBA, Salvador, BA, Brazil. [Prates, Deboraci Brito] Univ Fed,Bahia, Inst Ciencias Saude, Dept Biomorfol, BR-40110100 Salvador, BA, Brazil. [Andrade, Bruno B.] NIAID, Immunobiol Sect, Parasit Dis Lab, NIH, Bethesda, MD 20893 USA. [Brodskyn, Claudia I.; Barral, Aldina; Borges, Valria Matos] iii INCT Natl Inst Sci & Technol, Inst Invest Immunol, Sao Paulo, Brazil. [Bozza, Patrcia T.] Fundacao Oswaldo Cruz, Inst Oswaldo Cruz, Rio De Janeiro, RJ, Brazil. RP Borges, VM (reprint author), Oswaldo Cruz Fdn FIOCRUZ, Gonalo Moniz Res Ctr, Salvador, BA, Brazil. EM vborges@bahia.fiocruz.br RI Borges, Valeria/G-2009-2014; Araujo-Santos, Theo/F-9807-2014; OI Araujo-Santos, Theo/0000-0001-9861-6660; Borges, Valeria/0000-0002-2775-5409 FU Brazilian National Research Council (CNPq) INCT/CNPq [57.3879/2008-7]; Brazilian National Research Council (CNPq) [478480/2013-0, 202109/2010-0] FX This work was supported by the Brazilian National Research Council (CNPq) INCT/CNPq [Grant number: 57.3879/2008-7] (VMB); The Brazilian National Research Council (CNPq) [Grant number: 478480/2013-0 (VMB) and 202109/2010-0 (IAS)]. We thank Edvaldo Passos for technical assistance with the insect colony and Dr. Adriana Lanfredi for electron microscopy support. NR 36 TC 0 Z9 0 U1 0 U2 2 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1756-3305 J9 PARASITE VECTOR JI Parasites Vectors PD DEC 20 PY 2014 VL 7 AR 601 DI 10.1186/s13071-014-0601-8 PG 8 WC Parasitology SC Parasitology GA CA5KE UT WOS:000348946500001 ER PT J AU Ha, M Kraushaar, DC Zhao, KJ AF Ha, Misook Kraushaar, Daniel C. Zhao, Keji TI Genome-wide analysis of H3.3 dissociation reveals high nucleosome turnover at distal regulatory regions of embryonic stem cells SO EPIGENETICS & CHROMATIN LA English DT Article DE Histone variant; H3.3 dissociation; Nucleosome stability; Genome-wide chromatin dynamics ID HISTONE VARIANT H3.3; TRANSCRIPTION FACTORS; ACTIVE CHROMATIN; GENE-EXPRESSION; IN-VIVO; DIFFERENTIATION; DEPOSITION; DYNAMICS; PLURIPOTENT; H2A.Z AB Background: The histone variant H3.3 plays a critical role in maintaining the pluripotency of embryonic stem cells (ESCs) by regulating gene expression programs important for lineage specification. H3.3 is deposited by various chaperones at regulatory sites, gene bodies, and certain heterochromatic sites such as telomeres and centromeres. Using Tet-inhibited expression of epitope-tagged H3.3 combined with ChIP-Seq we undertook genome-wide measurements of H3.3 dissociation rates across the ESC genome and examined the relationship between H3.3-nucleosome turnover and ESC-specific transcription factors, chromatin modifiers, and epigenetic marks. Results: Our comprehensive analysis of H3.3 dissociation rates revealed distinct H3.3 dissociation dynamics at various functional chromatin domains. At transcription start sites, H3.3 dissociates rapidly with the highest rate at nucleosome-depleted regions (NDRs) just upstream of Pol II binding, followed by low H3.3 dissociation rates across gene bodies. H3.3 turnover at transcription start sites, gene bodies, and transcription end sites was positively correlated with transcriptional activity. H3.3 is found decorated with various histone modifications that regulate transcription and maintain chromatin integrity. We find greatly varying H3.3 dissociation rates across various histone modification domains: high dissociation rates at active histone marks and low dissociation rates at heterochromatic marks. Well-defined zones of high H3.3-nucleosome turnover were detected at binding sites of ESC-specific pluripotency factors and chromatin remodelers, suggesting an important role for H3.3 in facilitating protein binding. Among transcription factor binding sites we detected higher H3.3 turnover at distal cis-acting sites compared to proximal genic transcription factor binding sites. Our results imply that fast H3.3 dissociation is a hallmark of interactions between DNA and transcriptional regulators. Conclusion: Our study demonstrates that H3.3 turnover and nucleosome stability vary greatly across the chromatin landscape of embryonic stem cells. The presence of high H3.3 turnover at RNA Pol II binding sites at extragenic regions as well as at transcription start and end sites of genes, suggests a specific role for H3.3 in transcriptional initiation and termination. On the other hand, the presence of well-defined zones of high H3.3 dissociation at transcription factor and chromatin remodeler binding sites point to a broader role in facilitating accessibility. C1 [Ha, Misook] Samsung Elect Corp, Samsung Adv Inst Technol, Yongin 446712, Gyeonggi Do, South Korea. [Kraushaar, Daniel C.; Zhao, Keji] NHLBI, Syst Biol Ctr, NIH, Bethesda, MD 20892 USA. RP Ha, M (reprint author), Samsung Elect Corp, Samsung Adv Inst Technol, Yongin 446712, Gyeonggi Do, South Korea. EM misook.ha@gmail.com FU Division of Intramural Research, NHLBI, NIH, USA FX We thank the NHLBI DNA Sequencing Core facility for sequencing the ChIP-Seq and RNA-Seq libraries. The work was supported by the Division of Intramural Research, NHLBI, NIH, USA. NR 52 TC 3 Z9 3 U1 2 U2 5 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1756-8935 J9 EPIGENET CHROMATIN JI Epigenetics Chromatin PD DEC 20 PY 2014 VL 7 AR 38 DI 10.1186/1756-8935-7-38 PG 14 WC Genetics & Heredity SC Genetics & Heredity GA AZ0JE UT WOS:000347931100001 PM 25598842 ER PT J AU Yun, KS Ajima, R Sharma, N Costantini, F Mackem, S Lewandoski, M Yamaguchi, TP Perantoni, AO AF Yun, Kangsun Ajima, Rieko Sharma, Nirmala Costantini, Frank Mackem, Susan Lewandoski, Mark Yamaguchi, Terry P. Perantoni, Alan O. TI Non-canonical Wnt5a/Ror2 signaling regulates kidney morphogenesis by controlling intermediate mesoderm extension SO HUMAN MOLECULAR GENETICS LA English DT Article ID PLANAR CELL POLARITY; RECEPTOR TYROSINE KINASE; BRANCHING MORPHOGENESIS; ROBINOW-SYNDROME; ROR2; REVEALS; PATHWAY; TRACT; MOUSE; MICE AB Congenital anomalies of the kidney and urinary tract (CAKUT) affect about 1 in 500 births and are a major cause of morbidity in infants. Duplex collecting systems rank among the most common abnormalities of CAKUT, but the molecular basis for this defect is poorly understood. In mice, conditional deletion of Wnt5a in mesoderm results in bilateral duplex kidney and ureter formation. The ureteric buds(UBs) inmutants emerge as doublets from the intermediate mesoderm (IM)-derived nephric duct (ND) without anterior expansion of the glial cell line-derived neurotrophic factor (Gdnf) expression domain in the surrounding mesenchyme. Wnt5a is normally expressed in a graded manner at the posterior end of the IM, but its expression is down-regulated prior to UB outgrowth at E10.5. Furthermore, ablation of Wnt5a in the mesoderm with an inducible Cre at E7.5 results in duplex UBs, whereas ablation at E8.5 yields normal UB outgrowth, demonstrating that Wnt5a functions in IM development well before the formation of the metanephros. In mutants, the posterior ND is duplicated and surrounding Pax2-positive mesenchymal cells persist in the nephric cord, suggesting that disruption of normal ND patterning prompts the formation of duplex ureters and kidneys. Ror2homozygous mutants, which in frequently yield duplex collecting systems, show a dramatic increase in incidence with the additional deletion of one copy of Wnt5a, implicating this receptor in non-canonical Wnt5a signaling during IM development. This work provides the first evidence of a role of Wnt5a/Ror2 signaling in IM extension and offers new insights into the etiology of CAKUT and possible involvement of Wnt5a/Ror2 mutations. C1 [Yun, Kangsun; Ajima, Rieko; Sharma, Nirmala; Mackem, Susan; Lewandoski, Mark; Yamaguchi, Terry P.; Perantoni, Alan O.] NCI, Canc & Dev Biol Lab, NIH, Frederick, MD 21702 USA. [Costantini, Frank] Columbia Univ, Med Ctr, Dept Genet & Dev, New York, NY 10032 USA. RP Perantoni, AO (reprint author), NCI, Canc & Dev Biol Lab, NIH, Frederick, MD 21702 USA. EM perantoa@mail.nih.gov FU National Institutes of Health; National Cancer Institute; Center for Cancer Research FX This work was supported by the National Institutes of Health, National Cancer Institute and Center for Cancer Research. NR 36 TC 10 Z9 10 U1 0 U2 6 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 20 PY 2014 VL 23 IS 25 BP 6807 EP 6814 DI 10.1093/hmg/ddu397 PG 8 WC Biochemistry & Molecular Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Genetics & Heredity GA AZ0GB UT WOS:000347923000010 PM 25082826 ER PT J AU Keller, MF Reiner, AP Okada, Y van Rooij, FJA Johnson, AD Chen, MH Smith, AV Morris, AP Tanaka, T Ferrucci, L Zonderman, AB Lettre, G Harris, T Garcia, M Bandinelli, S Qayyum, R Yanek, LR Becker, DM Becker, LC Kooperberg, C Keating, B Reis, J Tang, H Boerwinkle, E Kamatani, Y Matsuda, K Kamatani, N Nakamura, Y Kubo, M Liu, SM Dehghan, A Felix, JF Hofman, A Uitterlinden, AG van Duijn, CM Franco, OH Longo, DL Singleton, AB Psaty, BM Evans, MK Cupples, LA Rotter, JI O'Donnell, CJ Takahashi, A Wilson, JG Ganesh, SK Nalls, MA AF Keller, Margaux F. Reiner, Alexander P. Okada, Yukinori van Rooij, Frank J. A. Johnson, Andrew D. Chen, Ming-Huei Smith, Albert V. Morris, Andrew P. Tanaka, Toshiko Ferrucci, Luigi Zonderman, Alan B. Lettre, Guillaume Harris, Tamara Garcia, Melissa Bandinelli, Stefania Qayyum, Rehan Yanek, Lisa R. Becker, Diane M. Becker, Lewis C. Kooperberg, Charles Keating, Brendan Reis, Jared Tang, Hua Boerwinkle, Eric Kamatani, Yoichiro Matsuda, Koichi Kamatani, Naoyuki Nakamura, Yusuke Kubo, Michiaki Liu, Simin Dehghan, Abbas Felix, Janine F. Hofman, Albert Uitterlinden, Andre G. van Duijn, Cornelia M. Franco, Oscar H. Longo, Dan L. Singleton, Andrew B. Psaty, Bruce M. Evans, Michelle K. Cupples, L. Adrienne Rotter, Jerome I. O'Donnell, Christopher J. Takahashi, Atsushi Wilson, James G. Ganesh, Santhi K. Nalls, Mike A. CA Charge Hematology Working Grp COGENT Working Grp BioBank Japan Project RIKEN TI Trans-ethnic meta-analysis of white blood cell phenotypes SO HUMAN MOLECULAR GENETICS LA English DT Article ID GENOME-WIDE ASSOCIATION; GENE-EXPRESSION; TRANSETHNIC METAANALYSIS; LEUKOCYTE COUNT; COMPLEX TRAITS; RECEPTOR; LOCI; VARIANTS; DISEASE; PROTEIN AB White blood cell (WBC) count is a common clinical measure used as a predictor of certain aspects of human health, including immunity and infection status. WBC count is also a complex trait that varies among individuals and ancestry groups. Differences in linkage disequilibrium structure and heterogeneity in allelic effects are expected to play a role in the associations observed between populations. Prior genome-wide association study (GWAS) meta-analyses have identified genomic loci associated with WBC and its subtypes, but much of the heritability of these phenotypes remains unexplained. Using GWAS summary statistics for over 50 000 individuals from three diverse populations (Japanese, African-American and European ancestry), a Bayesian model methodology was employed to account for heterogeneity between ancestry groups. This approach was used to perform a trans-ethnic meta-analysis of total WBC, neutrophil and monocyte counts. Ten previously known associations were replicated and six new loci were identified, including several regions harboring genes related to inflammation and immune cell function. Ninety-five percent credible interval regions were calculated to narrow the association signals and fine-map the putatively causal variants within loci. Finally, a conditional analysis was performed on the most significant SNPs identified by the trans-ethnic meta-analysis (MA), and nine secondary signals within loci previously associated with WBC or its subtypes were identified. This work illustrates the potential of trans-ethnic analysis and ascribes a critical role to multi-ethnic cohorts and consortia in exploring complex phenotypes with respect to variants that lie outside the European-biased GWAS pool. C1 [Keller, Margaux F.; Singleton, Andrew B.; Nalls, Mike A.] NIA, Neurogenet Lab, NIH, Bethesda, MD 20892 USA. [Harris, Tamara; Garcia, Melissa] NIA, Lab Epidemiol & Populat Sci, NIH, Bethesda, MD 20892 USA. [Tanaka, Toshiko; Ferrucci, Luigi] NIA, Longitudinal Studies Sect, Clin Res Branch, Intramural Res Program,NIH, Baltimore, MD 21224 USA. [Zonderman, Alan B.] NIA, Behav Epidemiol Sect, Lab Epidemiol & Populat Sci, Intramural Res Program,NIH, Baltimore, MD 21224 USA. [Longo, Dan L.] NIA, Genet Lab, NIH, Baltimore, MD 21224 USA. [Evans, Michelle K.] NIA, Hlth Dispar Res Sect, Clin Res Branch, NIH, Baltimore, MD 21224 USA. [Keller, Margaux F.] Temple Univ, Dept Biol Anthropol, Philadelphia, PA 19122 USA. [Reiner, Alexander P.] Univ Washington, Dept Epidemiol, Seattle, WA 98195 USA. [Psaty, Bruce M.] Univ Washington, Cardiovasc Hlth Res Unit, Seattle, WA 98195 USA. [Psaty, Bruce M.] Univ Washington, Dept Med, Seattle, WA USA. [Psaty, Bruce M.] Univ Washington, Dept Epidemiol & Hlth Serv, Seattle, WA 98195 USA. [Reiner, Alexander P.; Kooperberg, Charles] Fred Hutchinson Canc Res Ctr, Div Publ Hlth Sci, Seattle, WA 98104 USA. [Okada, Yukinori; Kamatani, Yoichiro; Kamatani, Naoyuki; Takahashi, Atsushi] RIKEN Ctr Integrat Med Sci, Lab Stat Anal, Yokohama, Kanagawa, Japan. [Kubo, Michiaki] RIKEN Ctr Integrat Med Sci, Lab Genotyping Dev, Yokohama, Kanagawa, Japan. [Okada, Yukinori] Tokyo Med & Dent Univ, Grad Sch Med & Dent Sci, Dept Human Genet & Dis Divers, Tokyo, Japan. [van Rooij, Frank J. A.; Dehghan, Abbas; Felix, Janine F.; Hofman, Albert; Uitterlinden, Andre G.; van Duijn, Cornelia M.; Franco, Oscar H.] Erasmus MC, Dept Epidemiol, Rotterdam, Netherlands. [Franco, Oscar H.] Erasmus MC, Dept Epidemiol, ErasmusAGE, Rotterdam, Netherlands. [Uitterlinden, Andre G.] Erasmus MC, Dept Internal Med, Rotterdam, Netherlands. [van Rooij, Frank J. A.; Dehghan, Abbas; Felix, Janine F.; Hofman, Albert; Uitterlinden, Andre G.; van Duijn, Cornelia M.; Franco, Oscar H.] Consortium Healthy Aging NG INCHA, Leiden, Netherlands. [Johnson, Andrew D.; O'Donnell, Christopher J.] NHLBI, Cardiovasc Epidemiol & Human Genom Branch, Div Intramural Res, Bethesda, MD 20892 USA. [Chen, Ming-Huei] Boston Univ, Sch Med, Dept Neurol, Boston, MA 02118 USA. [Johnson, Andrew D.; Chen, Ming-Huei; Cupples, L. Adrienne; O'Donnell, Christopher J.] NHLBI Framingham Heart Study, Bethesda, MD USA. [Smith, Albert V.] Iceland Heart Assoc, Kopavogur, Iceland. [Smith, Albert V.] Univ Iceland, Reykjavik, Iceland. [Morris, Andrew P.] Univ Oxford, Wellcome Trust Ctr Human Genet, Genet & Genom Epidemiol Unit, Oxford, England. [Morris, Andrew P.] Univ Liverpool, Dept Biostat, Liverpool L69 3BX, Merseyside, England. [Lettre, Guillaume] Montreal Heart Inst, Montreal, PQ H1T 1C8, Canada. [Lettre, Guillaume] Univ Montreal, Dept Med, Montreal, PQ H3C 3J7, Canada. [Bandinelli, Stefania] ASF, Geriatr Rehabil Unit, Florence, Italy. [Qayyum, Rehan; Yanek, Lisa R.; Becker, Diane M.; Becker, Lewis C.] Johns Hopkins Sch Med, Div Gen Internal Med, GeneSTAR Res Program, Baltimore, MD USA. [Becker, Lewis C.] Johns Hopkins Sch Med, Divis Cardiol, Baltimore, MD USA. [Keating, Brendan] Childrens Hosp Philadelphia, Ctr Appl Genom, Philadelphia, PA 19104 USA. [Keating, Brendan] Univ Penn, Dept Pediat, Philadelphia, PA 19104 USA. [Reis, Jared] NHLBI, Div Cardiovasc Sci, Bethesda, MD 20892 USA. [Tang, Hua] Stanford Univ, Sch Med, Stanford, CA 94305 USA. [Boerwinkle, Eric] Univ Texas Houston, Brown Fdn, Inst Mol Med Prevent Human Dis, Houston, TX USA. [Matsuda, Koichi; Nakamura, Yusuke] Univ Tokyo, Inst Med Sci, Ctr Human Genome, Mol Med Lab, Tokyo, Japan. [Nakamura, Yusuke] Univ Chicago, Dept Med, Chicago, IL 60637 USA. [Nakamura, Yusuke] Univ Chicago, Dept Surg, Ctr Personalized Therapeut, Chicago, IL 60637 USA. [Liu, Simin] Brown Univ, Dept Epidemiol, Providence, RI 02912 USA. [Liu, Simin] Brown Univ, Dept Med, Providence, RI 02912 USA. [Psaty, Bruce M.] Grp Hlth Cooperat Puget Sound, Grp Hlth Res Inst, Seattle, WA USA. [Cupples, L. Adrienne] Boston Univ, Dept Stat, Boston, MA 02215 USA. [Rotter, Jerome I.] Harbor UCLA Med Ctr, Los Angeles BioMed Res Inst, Inst Translat Genom & Populat Sci, Torrance, CA 90509 USA. [Rotter, Jerome I.] Harbor UCLA Med Ctr, Dept Pediat, Div Genet Outcomes, Torrance, CA 90509 USA. [Wilson, James G.] Univ Mississippi, Med Ctr, Dept Physiol & Biophys, Jackson, MS 39216 USA. [Ganesh, Santhi K.] Univ Michigan, Dept Internal Med, Div Cardiovasc Med, Ann Arbor, MI 48109 USA. [Ganesh, Santhi K.] Univ Michigan, Dept Human Genet, Ann Arbor, MI 48109 USA. RP Ganesh, SK (reprint author), Univ Michigan, Dept Internal Med, Div Cardiovasc Med, 1500 E Med Ctr Dr, Ann Arbor, MI 48109 USA. EM sganesh@med.umich.edu; nallsm@mail.nih.gov RI Singleton, Andrew/C-3010-2009; Meisinger, Christine/B-5358-2014; Gudnason, Vilmundur/K-6885-2015; Kamatani, Yoichiro/N-5513-2015; Smith, Albert/K-5150-2015; Kubo, Michiaki/N-7947-2015; Johnson, Andrew/G-6520-2013; OI Ouwehand, Willem/0000-0002-7744-1790; Dehghan, Abbas/0000-0001-6403-016X; Pirastu, Nicola/0000-0002-5363-3886; Melzer, David/0000-0002-0170-3838; Gudnason, Vilmundur/0000-0001-5696-0084; Zonderman, Alan B/0000-0002-6523-4778; Smith, Albert/0000-0003-1942-5845; Felix, Janine/0000-0002-9801-5774 FU Japan Society of the Promotion of Science (JSPS); Wellcome Trust [WT098017, WT090532, WT064890]; NIA/NIH [AG000932-2 (2009)]; NIH [N01-AG-12100, R01 HL71862-06]; NIA Intramural Research Program; Hjartavernd (the Icelandic Heart Association); Althingi (the Icelandic Parliament); National Heart, Lung, and Blood Institute [HHSN268201100005C, HHSN268201100006C, HHSN2682 01100007C, HHSN268201100008C, HHSN268201100009C, HHSN268201100010C, HHSN268201100011C, HHSN268 201100012C, R01HL087641, R01HL59367, R01HL086694]; National Human Genome Research Institute [U01HG 004402, U01HG004402]; National Institutes of Health [HHSN 268200625226C, HHSN268200782096C, HHSN268200625226C, UL1RR025005]; NIH Roadmap for Medical Research [UL1RR025005]; National Heart, Lung, and Blood Institute's Framingham Heart Study [N01-HC-25195]; Affymetrix for genotyping services [N02-HL-6-4278]; Robert Dawson Evans Endowment of the Department of Medicine at the Boston University School of Medicine; Boston Medical Center; Intramural Research Program of the NIH, National Institute on Aging, NIA [N01AG62101, N01AG62103, N01AG 62106]; NIA [N01AG62101, N01AG62103, 1R01AG032098-01A1, N01AG62106]; 'targeted project' by the Italian Ministry of Health [ICS 110.1RS97.71]; Italian Ministry of Health; US National Institute on Aging [N01-AG-916413, N01-AG-821336, 263 MD 9164 13, 263 MD 821336]; Intramural Research Program, National Institute on Aging, National Institutes of Health, USA; Erasmus Medical Center; Erasmus University, Rotterdam; Netherlands Organization for the Health Research and Development (ZonMw); Research Institute for Diseases in the Elderly (RIDE); Ministry of Education, Culture and Science; Ministry for Health, Welfare and Sports; European Commission (DG XII); Municipality of Rotterdam; Broad Institute [N01-HC-65226]; University of North Carolina at Chapel Hill [N01-HC-55015]; Baylor Medical College [N01-HC-55016]; University of Mississippi Medical Center [N01-HC-55021]; University of Minnesota [N01-HC-55019]; Johns Hopkins University [N01-HC-55020]; University of Texas Houston [N01-HC-55017]; University of North Carolina [N01-HC-55018]; Intramural Research Program of the NIH, National Institute on Aging; National Center on Minority Health and Health Disparities [Z01-AG000513, 2009-149]; National Heart, Lung, and Blood Institute (NHLBI) through the PROGENI [U01 HL72518]; STAMPEED consortia [R01 HL087698-01]; NIH/National Institute of Nursing Research [R01 NR08153]; NIH/National Center for Research Resources [M01-RR000052]; National Heart, Lung, and Blood Institute, National Institutes of Health, US Department of Health and Human Services [N01WH22110, 24152, 32100-2, 32105-6, 32108-9, 32111-13, 32115, 32118-32119, 32122, 42107-26, 42129-32, 44221]; National Institute of Neurological Disorders and Stroke; ARRA [N000949304]; US Public Health Service Resource Grant from the National Center for Research Resources [RR03655]; Ministry of Education, Culture, Sports, Science and Technology, Japan; The National Heart, Lung, and Blood Institute [HHSN268 201100006C, HHSN268201100007C, HHSN26820 1100011C, HHSN268201100012C, R01HL 59367, N01-HC-35129, N01-HC-45133]; National Heart, Lung, and Blood Institute. [N01-HC-75150, N01-HC-85079, N01-HC-85080, N01-HC-85081, N01-HC-85082, N01-HC-85083, N01-HC-85084, N01-HC-85085, N01-HC-85086, N01 HC-15103, N01 HC-55222, U01 HL080295]; [P30HL101290] FX Y.O. is supported by a grant from the Japan Society of the Promotion of Science (JSPS). The development of the software package MANTRA was supported by Wellcome Trust (grant nos WT098017, WT090532 and WT064890). S.K.G. was supported in part by P30HL101290. Funding for CHARGE was made possible by NIA/NIH contract AG000932-2 (2009) Characterization of Normal Genomic Variability. The Age, Gene/Environment Susceptibility Reykjavik Study is funded by NIH contract N01-AG-12100, the NIA Intramural Research Program, Hjartavernd (the Icelandic Heart Association) and the Althingi (the Icelandic Parliament). The Atherosclerosis Risk in the Communities Study is carried out as a collaborative study supported by National Heart, Lung, and Blood Institute contracts (HHSN268201100005C, HHSN268201100006C, HHSN2682 01100007C, HHSN268201100008C, HHSN268201100009C, HHSN268201100010C, HHSN268201100011C and HHSN268 201100012C), R01HL087641, R01HL59367 and R01HL086694; National Human Genome Research Institute contract (U01HG 004402) and National Institutes of Health contract (HHSN 268200625226C). The authors thank the staff and participants of the ARIC study for their important contributions. Infrastructure was partly supported by grant number UL1RR025005, a component of the National Institutes of Health and NIH Roadmap for Medical Research. The National Heart, Lung, and Blood Institute's Framingham Heart Study is a joint project of the National Institutes of Health and Boston University School of Medicine and was supported by the National Heart, Lung, and Blood Institute's Framingham Heart Study (contract No. N01-HC-25195) and its contract with Affymetrix for genotyping services (contract No. N02-HL-6-4278). Analyses reflect the efforts and resource development from the Framingham Heart Study investigators participating in the SNP Health Association Resource (SHARe) project. A portion of this research was conducted using the Linux Cluster for Genetic Analysis (LinGA-II) funded by the Robert Dawson Evans Endowment of the Department of Medicine at the Boston University School of Medicine and Boston Medical Center. The Health ABC Study was supported in part by the Intramural Research Program of the NIH, National Institute on Aging, NIA contracts N01AG62101, N01AG62103 and N01AG 62106. The GWAS was funded by NIA grant 1R01AG032098-01A1 to Wake Forest University Health Sciences and genotyping services were provided by the Center for Inherited Disease Research (CIDR). CIDR is fully funded through a federal contract from the National Institutes of Health to The Johns Hopkins University (contract number HHSN268200782096C). The InChianti Study was supported as a 'targeted project' (ICS 110.1RS97.71) by the Italian Ministry of Health, by the US National Institute on Aging (contracts N01-AG-916413, N01-AG-821336, 263 MD 9164 13 and 263 MD 821336) and in part by the Intramural Research Program, National Institute on Aging, National Institutes of Health, USA. The generation and management of GWAS genotype data for the Rotterdam Study is supported by the Netherlands Organization of Scientific Research NWO Investments (no. 175.010.2005.011, 911-03-012), the Research Institute for Diseases in the Elderly (014-93-015; RIDE2), EUROSPAN (European Special Populations Research Network; LSHG-CT-2006-01947), the Netherlands Organization for Scientific Research (Pionier, 047.016.009, 047.017.; 043; 050-060-810), Erasmus Medical Center and the Centre for Medical Systems Biology (CMSB I and II and Grand; National Genomics Initiative) of the Netherlands Genomics Initiative (NGI); The Rotterdam Study is further funded by Erasmus Medical Center and Erasmus University, Rotterdam, Netherlands Organization for the Health Research and Development (ZonMw), the Research Institute for Diseases in the Elderly (RIDE), the Ministry of Education, Culture and Science, the Ministry for Health, Welfare and Sports, the European Commission (DG XII) and the Municipality of Rotterdam. Funding for COGENT was obtained through the Broad Institute (N01-HC-65226) to create this genotype/phenotype database for wide dissemination to the biomedical research community. The Atherosclerosis Risk in Communities Study is carried out as a collaborative study supported by National Heart, Lung, and Blood Institute contracts (HHSN268201100005C, HHSN268 201100006C, HHSN268201100007C, HHSN268201100008C, HHSN268201100009C, HHSN268201100010C, HHSN26820 1100011C and HHSN268201100012C), R01HL087641, R01HL 59367 and R01HL086694; National Human Genome Research Institute (contract U01HG004402) and National Institutes of Health (contract HHSN268200625226C). The authors thank the staff and participants of the ARIC study for their important contributions. Infrastructure was partly supported by grant number UL1RR025005, a component of the National Institutes of Health and NIH Roadmap for Medical Research. ARIC is also supported by University of North Carolina at Chapel Hill (funded by N01-HC-55015), Baylor Medical College (N01-HC-55016), University of Mississippi Medical Center (N01-HC-55021), University of Minnesota (N01-HC-55019), Johns Hopkins University (N01-HC-55020), University of Texas Houston (N01-HC-55017) and University of North Carolina (N01-HC-55018). Coronary Artery Risk in Young Adults (CARDIA): University of Alabama at Birmingham (N01-HC-48047), University of Minnesota (N01-HC-48048), Northwestern University (N01-HC-48049), Kaiser Foundation Research Institute (N01-HC-48050), University of Alabama at Birmingham (N01-HC-95095), Tufts-New England Medical Center (N01-HC-45204), Wake Forest University (N01-HC-45205), Harbor-UCLA Research and Education Institute (N01-HC-05187), University of California, Irvine (N01-HC-45134 and N01-HC-95100). Jackson Heart Study (JHS): Jackson State University (N01-HC-95170), University of Mississippi (N01-HC-95171), Tougaloo College (N01-HC-95172). Healthy Aging in Neighborhoods of Diversity across the Life Span Study (HANDLS): This research was supported by the Intramural Research Program of the NIH, National Institute on Aging and the National Center on Minority Health and Health Disparities (intramural project # Z01-AG000513 and human subjects protocol # 2009-149). Health ABC: This research was supported by NIA contracts N01AG62101, N01AG62103 and N01AG62106. The GWAS was funded by NIA grant 1R01AG032098-01A1 to Wake Forest University Health Sciences and genotyping services were provided by the Center for Inherited Disease Research (CIDR). CIDR is fully funded through a federal contract from the National Institutes of Health to The Johns Hopkins University (contract number HHSN268200782096C). This research was supported in part by the Intramural Research Program of the NIH, National Institute on Aging. Gene STAR Acknowledgement: This research was supported by the National Heart, Lung, and Blood Institute (NHLBI) through the PROGENI (U01 HL72518) and STAMPEED (R01 HL087698-01) consortia.; Additional support was provided by grants from the NIH/National Institute of Nursing Research (R01 NR08153) and the NIH/National Center for Research Resources (M01-RR000052) to the Johns Hopkins General Clinical Research Center. WHI: The WHI program is funded by the National Heart, Lung, and Blood Institute, National Institutes of Health, US Department of Health and Human Services, through contracts N01WH22110, 24152, 32100-2, 32105-6, 32108-9, 32111-13, 32115, 32118-32119, 32122, 42107-26, 42129-32 and 44221. The Cardiovascular Health Study (CHS) is supported from contracts N01-HC-35129, N01-HC-45133, N01-HC-75150, N01-HC-85079 through N01-HC-85086, N01 HC-15103, N01 HC-55222 and U01 HL080295 from the National Heart, Lung, and Blood Institute, with additional contribution from the National Institute of Neurological Disorders and Stroke. Additional support for this work was provided by NIH R01 HL71862-06 and ARRA N000949304 (to A.P.R.). Some of the results of this paper were obtained by using the program package SAGE., which is supported by a US Public Health Service Resource Grant (RR03655) from the National Center for Research Resources. The funders had no role in study design, data collection and analysis, decision to publish or preparation of the manuscript. Funding for RIKEN and the BioBank Japan Project was supported by Ministry of Education, Culture, Sports, Science and Technology, Japan. The funders had no role in study design, data collection and analysis, decision to publish or preparation of the manuscript. NR 68 TC 6 Z9 6 U1 1 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 20 PY 2014 VL 23 IS 25 BP 6944 EP 6960 DI 10.1093/hmg/ddu401 PG 17 WC Biochemistry & Molecular Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Genetics & Heredity GA AZ0GB UT WOS:000347923000022 PM 25096241 ER PT J AU Qi, QB Kilpelainen, TO Downer, MK Tanaka, T Smith, CE Sluijs, I Sonestedtl, E Chull, AY Renstrom, F Lin, XC Angquist, LH Huang, JY Liu, ZH Li, YP Ali, MA Xu, M Ahluwalia, TS Boer, JMA Chen, P Daimon, M Eriksson, J Perola, M Friedlander, Y Gao, YT Heppe, DHM Holloway, JW Houston, DK Kanoni, S Kim, YM Laaksonen, MA Jaaskelainen, T Lee, NR Lehtimaki, T Lemaitre, RN Lu, W Luben, RN Manichaiku, A Mannisto, S Marques-Vidal, P Monda, KL Ngwa, JS Perusse, L van Rooij, FJA Xiang, YB Wen, WQ Wojczynski, MK Zhu, JW Borecki, IB Bouchard, C Cai, QY Cooper, C Dedoussis, GV Deloukas, P Ferrucci, L Forouhi, NG Hansen, T Christiansen, L Hofman, A Johansson, I Jorgensen, T Karasawa, S Khaw, KT Kim, MK Kristiansson, K Li, HX Lin, X Liu, YM Lohman, KK Long, JR Mikkila, V Mozaffarian, D North, K Pedersen, O Raitakari, O Rissanen, H Tuomilehto, J van der Schouw, YT Uitterlinden, AG Zillikens, MC Franco, OH Tai, ES Shu, XO Siscovick, DS Toft, U Verschuren, WMM Vollenweider, P Wareham, NJ Witteman, JCM Zheng, W Ridker, PM Kang, JH Liang, LM Jensen, MK Curhan, GC Pasquale, LR Hunter, DJ Mohlke, KL Uusitupa, M Cupples, LA Rankinen, T Orho-Melander, M Wang, T Chasman, DI Franks, PW Sorensen, TIA Hu, FB Loos, RJF Nettleton, JA Qi, L AF Qi, Qibin Kilpelainen, Tuomas O. Downer, Mary K. Tanaka, Toshiko Smith, Caren E. Sluijs, Ivonne Sonestedtl, Emily Chull, Audrey Y. Renstrom, Frida Lin, Xiaochen Angquist, Lars H. Huang, Jinyan Liu, Zhonghua Li, Yanping Ali, Muhammad Asif Xu, Min Ahluwalia, Tarunveer Singh Boer, Jolanda M. A. Chen, Peng Daimon, Makoto Eriksson, Johan Perola, Markus Friedlander, Yechiel Gao, Yu-Tang Heppe, Denise H. M. Holloway, John W. Houston, Denise K. Kanoni, Stavroula Kim, Yu-Mi Laaksonen, Maarit A. Jaaskelainen, Tiina Lee, Nanette R. Lehtimaki, Terho Lemaitre, Rozenn N. Lu, Wei Luben, Robert N. Manichaiku, Ani Mannisto, Satu Marques-Vidal, Pedro Monda, Keri L. Ngwa, Julius S. Perusse, Louis van Rooij, Frank J. A. Xiang, Yong-Bing Wen, Wanqing Wojczynski, Mary K. Zhu, Jingwen Borecki, Ingrid B. Bouchard, Claude Cai, Qiuyin Cooper, Cyrus Dedoussis, George V. Deloukas, Panos Ferrucci, Luigi Forouhi, Nita G. Hansen, Torben Christiansen, Lene Hofman, Albert Johansson, Ingegerd Jorgensen, Torben Karasawa, Shigeru Khaw, Kay-Tee Kim, Mi-Kyung Kristiansson, Kati Li, Huaixing Lin, Xu Liu, Yongmei Lohman, Kurt K. Long, Jirong Mikkila, Vera Mozaffarian, Dariush North, Kari Pedersen, Oluf Raitakari, Olli Rissanen, Harri Tuomilehto, Jaakko van der Schouw, Yvonne T. Uitterlinden, Andre G. Zillikens, M. Carola Franco, Oscar H. Tai, E. Shyong Shu, Xiao Ou Siscovick, David S. Toft, Ulla Verschuren, W. M. Monique Vollenweider, Peter Wareham, Nicholas J. Witteman, Jacqueline C. M. Zheng, Wei Ridker, Paul M. Kang, Jae H. Liang, Liming Jensen, Majken K. Curhan, Gary C. Pasquale, Louis R. Hunter, David J. Mohlke, Karen L. Uusitupa, Matti Cupples, L. Adrienne Rankinen, Tuomo Orho-Melander, Marju Wang, Tao Chasman, Daniel I. Franks, Paul W. Sorensen, Thorkild I. A. Hu, Frank B. Loos, Ruth J. F. Nettleton, Jennifer A. Qi, Lu TI FTO genetic variants, dietary intake and body mass index: insights from 177 330 individuals SO HUMAN MOLECULAR GENETICS LA English DT Article ID OBESITY-ASSOCIATED GENE; TIME PHYSICAL-ACTIVITY; FAT MASS; ENERGY-INTAKE; FOOD-INTAKE; METABOLIC-RATE; ASSOCIATION; CHILDREN; RS9939609; GENOTYPE AB FTO is the strongest known genetic susceptibility locus for obesity. Experimental studies in animals suggest the potential roles of FTO in regulating food intake. The interactive relation among FTO variants, dietary intake and body mass index (BMI) is complex and results from previous often small-scale studies in humans are highly inconsistent. We performed large-scale analyses based on data from 177 330 adults (154 439 Whites, 5776 African Americans and 17 115 Asians) from 40 studies to examine: (i) the association between the FTO-rs9939609 variant (or a proxy single-nucleotide polymorphism) and total energy and macronutrient intake and (ii) the interaction between the FTO variant and dietary intake on BM I. The minor allele (A-allele) of the FTO-rs9939609 variant was associated with higher BMI in Whites (effect per allele = 0.34 [0.31, 0.37] kg/m(2), P = 1.9 x 10(-105)), and all participants (0.30 [0.30, 0.35] kg/m(2), P = 3.6 x 10(-107)). The BMI-increasing allele of the FTO variant showed a significant association with higher dietary protein intake (effect per allele = 0.08 [0.06, 0.10] %, P = 2.4 x 10(-16)), and relative weak associations with lower total energy intake (-6.4 [- 10.1, -2.6] kcal/day, P = 0.001) and lower dietary carbohydrate intake (-0.07 [- 0.11, -0.02] %, P = 0.004). The associations with protein (P = 7.5 x 10(-9)) and total energy (P = 0.002) were attenuated but remained significant after adjustment for BMI. We did not find significant interactions between the FTO variant and dietary intake of total energy, protein, carbohydrate or fat on BMI. Our findings suggest a positive association between the BMI-increasing allele of FTO variant and higher dietary protein intake and offer insight into potential link between FTO, dietary protein intake and adiposity. C1 [Qi, Qibin; Wang, Tao] Albert Einstein Coll Med, Dept Epidemiol, Bronx, NY 10467 USA. [Qi, Qibin; Downer, Mary K.; Li, Yanping; Ali, Muhammad Asif; Xu, Min; Mozaffarian, Dariush; Jensen, Majken K.; Hunter, David J.; Franks, Paul W.; Hu, Frank B.; Qi, Lu] Harvard Univ, Sch Publ Hlth, Dept Nutr, Boston, MA 02115 USA. [Lin, Xiaochen; Liu, Zhonghua; Mozaffarian, Dariush; Liang, Liming; Jensen, Majken K.; Curhan, Gary C.; Hunter, David J.; Franks, Paul W.; Hu, Frank B.] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. [Kilpelainen, Tuomas O.; Forouhi, Nita G.; Wareham, Nicholas J.; Loos, Ruth J. F.] Univ Cambridge, Sch Clin Med, Inst Metab Sci, MRC Epidemiol Unit, Cambridge, England. [Kilpelainen, Tuomas O.; Ahluwalia, Tarunveer Singh; Hansen, Torben; Pedersen, Oluf; Sorensen, Thorkild I. A.] Univ Copenhagen, Fac Hlth & Med Sci, Sect Metab Genet, Novo Nordisk Fdn Ctr Basic Metab Res, Copenhagen, Denmark. [Ahluwalia, Tarunveer Singh] Univ Copenhagen, Fac Hlth & Med Sci, Copenhagen Prospect Studies Asthma Childhood, Copenhagen, Denmark. [Tanaka, Toshiko; Ferrucci, Luigi] NIA, Translat Gerontol Branch, Baltimore, MD 21224 USA. [Smith, Caren E.] Tufts Univ, Jean Mayer USDA HNRCA, Nutr & Genom Lab, Boston, MA 02111 USA. 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[Perola, Markus; Laaksonen, Maarit A.; Mannisto, Satu; Kristiansson, Kati; Rissanen, Harri; Tuomilehto, Jaakko] Natl Inst Hlth & Welf, Helsinki, Finland. [Perola, Markus] Univ Tartu, Estonian Genome Ctr, EE-50090 Tartu, Estonia. [Friedlander, Yechiel] Hebrew Univ Jerusalem, Sch Publ Hlth, Jerusalem, Israel. [Gao, Yu-Tang; Xiang, Yong-Bing] Shanghai Jiao Tong Univ, Sch Med, Renji Hosp, Shanghai Canc Inst, Shanghai 200030, Peoples R China. [Heppe, Denise H. M.] Erasmus MC, Generat Study Grp R, Rotterdam, Netherlands. [Heppe, Denise H. M.; van Rooij, Frank J. A.; Hofman, Albert; Uitterlinden, Andre G.; Franco, Oscar H.; Witteman, Jacqueline C. M.] Erasmus MC, Dept Epidemiol, Rotterdam, Netherlands. [Heppe, Denise H. M.] Erasmus MC, Dept Pediat, Rotterdam, Netherlands. [Uitterlinden, Andre G.; Zillikens, M. Carola] Erasmus MC, Dept Internal Med, Rotterdam, Netherlands. [Holloway, John W.] Univ Southampton, Fac Med, Southampton SO9 5NH, Hants, England. [Houston, Denise K.] Wake Forest Sch Med, Dept Internal Med, Sect Gerontol & Geriatr Med, Winston Salem, NC USA. [Liu, Yongmei] Wake Forest Sch Med, Div Publ Hlth Sci, Dept Epidemiol, Winston Salem, NC USA. [Lohman, Kurt K.] Wake Forest Sch Med, Div Publ Hlth Sci, Dept Biostat Sci, Winston Salem, NC USA. [Kanoni, Stavroula; Deloukas, Panos] Queen Mary Univ London, Barts & London Sch Med & Dent, William Harvey Res Inst, London EC1M 6BQ, England. [Kim, Yu-Mi] Dong A Univ, Coll Med, Dept Prevent Med, Pusan, South Korea. [Jaaskelainen, Tiina; Uusitupa, Matti] Univ Eastern Finland, Inst Publ Hlth & Clin Nutr, Kuopio, Finland. [Lee, Nanette R.] Univ San Carlos, U5C Off Populat Studies Fdn Inc, Cebu, Philippines. [Lehtimaki, Terho] Univ Tampere, Dept Clin Chem, Fimlab Labs, FIN-33101 Tampere, Finland. [Lehtimaki, Terho] Univ Tampere, Sch Med, FIN-33101 Tampere, Finland. [Lemaitre, Rozenn N.; Siscovick, David S.] Univ Washington, Dept Med, Cardiovasc Hlth Res Unit, Seattle, WA USA. [Siscovick, David S.] Univ Washington, Dept Epidemiol, Cardiovasc Hlth Res Unit, Seattle, WA 98195 USA. [Lu, Wei] Shanghai Inst Prevent Med, Shanghai, Peoples R China. [Luben, Robert N.; Khaw, Kay-Tee] Univ Cambridge, Inst Publ Hlth, Dept Publ Hlth & Primary Care, Cambridge, England. [Manichaiku, Ani] Univ Virginia, Ctr Publ Hlth Genom, Charlottesville, VA USA. [Manichaiku, Ani] Univ Virginia, Dept Publ Hlth Sci, Div Biostat & Epidemiol, Charlottesville, VA USA. [Marques-Vidal, Pedro] Inst Social & Prevent Med, CH-1010 Lausanne, Switzerland. [Marques-Vidal, Pedro; Vollenweider, Peter] CHU Vaudois, Dept Med, CH-1011 Lausanne, Switzerland. [Monda, Keri L.; North, Kari] Univ N Carolina, Dept Epidemiol, Chapel Hill, NC USA. [North, Kari] Univ N Carolina, Carolina Ctr Genome Sci, Chapel Hill, NC USA. [Mohlke, Karen L.] Univ N Carolina, Dept Genet, Chapel Hill, NC USA. [Monda, Keri L.] Amgen Inc, Ctr Observat Res, Thousand Oaks, CA 91320 USA. [Ngwa, Julius S.; Cupples, L. Adrienne] Boston Univ, Sch Publ Hlth, Dept Biostat, Boston, MA USA. [Perusse, Louis] Univ Laval, Dept Kinesiol, Ste Foy, PQ, Canada. [van Rooij, Frank J. A.; Hofman, Albert; Uitterlinden, Andre G.; Zillikens, M. Carola; Franco, Oscar H.; Witteman, Jacqueline C. M.] NGI NCHA, Leiden, Netherlands. [Wen, Wanqing; Cai, Qiuyin; Long, Jirong; Shu, Xiao Ou; Zheng, Wei] Vanderbilt Univ, Sch Med, Vanderbilt Ingram Canc Ctr, Dept Med,Vanderbilt Epidemiol Ctr,Div Epidemiol, Nashville, TN 37212 USA. [Wojczynski, Mary K.; Borecki, Ingrid B.] Washington Univ, Sch Med, Dept Genet, St Louis, MO 63110 USA. [Zhu, Jingwen; Li, Huaixing; Lin, Xu] Chinese Acad Sci, Shanghai Inst Biol Sci, Inst Nutr Sci, Key Lab Nutr & Metab, Shanghai, Peoples R China. [Zhu, Jingwen; Li, Huaixing; Lin, Xu] Chinese Acad Sci, Grad Sch, Shanghai, Peoples R China. [Bouchard, Claude; Rankinen, Tuomo] Pennington Biomed Res Ctr, Human Genom Lab, Baton Rouge, LA 70808 USA. [Cooper, Cyrus] Univ Southampton, Southampton Gen Hosp, MRC Lifecourse Epidemiol Unit, Southampton SO16 6YD, Hants, England. [Cooper, Cyrus] Univ Southampton, Natl Inst Hlth Res Biomed Res Ctr, Southampton SO16 6YD, Hants, England. [Cooper, Cyrus] Univ Hosp Southampton NHS Fdn Trust, Southampton SO16 6YD, Hants, England. [Cooper, Cyrus] Univ Oxford, Natl Inst Hlth Res Musculoskeletal Biomed Res Uni, Oxford OX3 7LE, England. [Dedoussis, George V.] Harokopio Univ, Dept Dietet Nutr, Athens, Greece. [Deloukas, Panos] Wellcome Trust Sanger Inst, Cambridge CB10 1SA, England. [Deloukas, Panos] PACER HD, Jeddah 21589, Saudi Arabia. [Tuomilehto, Jaakko] King Abdulaziz Univ, Diabet Res Grp, Jeddah 21589, Saudi Arabia. [Christiansen, Lene] Univ Southern Denmark, Inst Publ Hlth, Danish Twin Registry, Odense, Denmark. [Johansson, Ingegerd] Umea Univ, Dept Odontol, Umea, Sweden. [Franks, Paul W.] Umea Univ, Dept Publ Hlth & Clin Med, Genet Epidemiol & Clin Res Grp, Umea, Sweden. [Jorgensen, Torben; Toft, Ulla] Glostrup Univ Hosp, Res Ctr Prevent & Hlth, Glostrup, Denmark. [Kim, Mi-Kyung] Hanyang Univ, Coll Med, Dept Prevent Med, Seoul 133791, South Korea. [Mikkila, Vera; Raitakari, Olli] Univ Turku, Res Ctr Appl & Prevent Cardiovasc Med, Turku, Finland. [Mozaffarian, Dariush] Tufts Univ, Friedman Sch Nutr Sci & Policy, Boston, MA 02111 USA. [Raitakari, Olli] Univ Turku, Dept Clin Physiol & Nucl Med, Turku, Finland. [Raitakari, Olli] Turku Univ Hosp, FIN-20520 Turku, Finland. [Tuomilehto, Jaakko] Danube Univ Krems, Ctr Vasc Prevent, A-3500 Krems, Austria. [Tuomilehto, Jaakko] Hosp Univ LaPaz IdiPAZ, Inst Invest Sanitaria, Madrid, Spain. [Tai, E. Shyong] Duke Natl Univ Singapore, Grad Sch Med, Singapore, Singapore. [Pasquale, Louis R.] Harvard Univ, Sch Med, Dept Ophthalmol, Mass Eye & Ear Infirm, Boston, MA USA. [Uusitupa, Matti] Kuopio Univ Hosp, Res Unit, SF-70210 Kuopio, Finland. [Cupples, L. Adrienne] Framingham Heart Dis Epidemiol Study, Framingham, MA USA. [Loos, Ruth J. F.] Mt Sinai Sch Med, Dept Prevent Med, Mindich Child Hlth & Dev Inst, Genet Obes & Related Metab Traits Program,Charles, New York, NY USA. [Nettleton, Jennifer A.] Univ Texas Hlth Sci Ctr Houston, Div Epidemiol Human Genet & Environm Sci, Houston, TX 77030 USA. RP Qi, L (reprint author), Harvard Univ, Sch Publ Hlth, Dept Nutr, 665 Huntington Ave, Boston, MA 02115 USA. EM nhlqi@channing.harvard.edu RI Holloway, John/B-5424-2009; Colaus, PsyColaus/K-6607-2013; Chen, Peng/E-5546-2015; Lin, Xiaochen/P-6460-2015; Sonestedt, Emily/I-3814-2016; Bouchard, Claude/A-7637-2009; Deloukas, Panos/B-2922-2013 OI Forouhi, Nita/0000-0002-5041-248X; Jorgensen, Torben/0000-0001-9453-2830; Tai, E Shyong/0000-0003-2929-8966; Franks, Paul/0000-0002-0520-7604; Kristiansson, Kati/0000-0003-4688-107X; Mannisto, Satu/0000-0002-8668-3046; Holloway, John/0000-0001-9998-0464; Chen, Peng/0000-0002-1422-4641; Luben, Robert/0000-0002-5088-6343; Sonestedt, Emily/0000-0002-0747-4562; Deloukas, Panos/0000-0001-9251-070X FU Canadian Institutes of Health Research [GR-15187, MOP-77652]; Cancer Research UK [, 14136]; FIC NIH HHS [TW008288, TW05596]; Medical Research Council [, G0401527, G0701863, G1000143, MC_U106179471, MC_UP_A100_1003, MC_UP_A620_1014, MC_UU_12011/1, MC_UU_12015/1, MC_UU_12015/5]; NCATS NIH HHS [UL1 TR000124, UL1TR000124]; NCI NIH HHS [R01CA148667, CA047988, CA055075, CA49449, CA87969, P30 CA016086, R01CA064277, R01CA082729, R01CA092585, R01CA122364, R01CA124558, R01CA82729, R37CA070867, U54CA155626, UM1 CA173640, UM1 CA182910]; NCRR NIH HHS [RR-024156, RR20649, UL1RR025005]; NEI NIH HHS [EY015473, R01 EY015473]; NHGRI NIH HHS [U01 HG004728, U01HG004399, U01HG004402, U01HG004728-02]; NHLBI NIH HHS [5R01 HL08770003, 5R01 HL08821502, HL-45670, HL043851, HL071981, HL073168, HL080295, HL080467, HL085144, HL085251, HL087652, HL088521, HL103612, HL105756, HL120393, HL34594, K08 HL112845, N01-HC-25195, N01-HC-95159, N01-HC-95169, N01HC55222, N01HC85079, N01HC85080, N01HC85081, N01HC85082, N01HC85083, N01HC85086, N02-HL-6-4278, N02‐HL‐6‐4278, R01 HL034594, R01 HL105756, R01 HL120393, R01HL071051, R01HL071205, R01HL071250, R01HL071251, R01HL071252, R01HL071258, R01HL071259, R01HL085710, R01HL086694, R01HL087641, R01HL59367]; NIA NIH HHS [AG023629, N01-AG-6-2101, N01-AG-6-2103, N01-AG-6-2106, R01-AG032098]; NIDDK NIH HHS [5P30DK46200, 5R01 DK06833603, 5R01 DK07568102, DK063491, DK078150, DK080140, DK091718, DK46200, DK56350, DK58845, DK70756, P30 DK046200, R01 DK078150, R01 DK089256, R01 DK091718]; NIEHS NIH HHS [ES10126, P30 ES010126]; NIMHD NIH HHS [263 MD 821336, 263 MD 9164]; PHS HHS [HHSN268200625226C, HHSN268200782096C, HHSN268200800007C, HHSN268201100005C, HHSN268201100006C, HHSN268201100007C, HHSN268201100008C, HHSN268201100009C, HHSN268201100010C, HHSN268201100011C, HHSN268201100012C, HHSN268201200036C] NR 52 TC 24 Z9 24 U1 3 U2 23 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 20 PY 2014 VL 23 IS 25 BP 6961 EP 6972 DI 10.1093/hmg/ddu411 PG 12 WC Biochemistry & Molecular Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Genetics & Heredity GA AZ0GB UT WOS:000347923000023 PM 25104851 ER PT J AU Gabizon, A Bradbury, M Prabhakar, U Zamboni, W Libutti, S Grodzinski, P AF Gabizon, Alberto Bradbury, Michelle Prabhakar, Uma Zamboni, William Libutti, Steven Grodzinski, Piotr TI Cancer nanomedicines: closing the translational gap SO LANCET LA English DT Editorial Material ID PERSONALIZED MEDICINE; NANOPARTICLES C1 [Gabizon, Alberto] Shaare Zedek Med Ctr, Jerusalem, Israel. [Gabizon, Alberto] Hebrew Univ Jerusalem, Sch Med, IL-91010 Jerusalem, Israel. [Bradbury, Michelle] Cornell Univ, Sloan Kettering Inst Canc Res, New York, NY 10021 USA. [Bradbury, Michelle] Cornell Univ, Weill Med Coll, New York, NY 10021 USA. [Prabhakar, Uma; Grodzinski, Piotr] NCI, Alliance Nanotechnol Canc, Bethesda, MD 20892 USA. [Zamboni, William] Univ N Carolina, UNC Lineberger Comprehens Canc Ctr, UNC Eshelman Sch Pharm, Chapel Hill, NC USA. [Libutti, Steven] Albert Einstein Coll Med, New York, NY USA. RP Grodzinski, P (reprint author), NCI, Alliance Nanotechnol Canc, Bethesda, MD 20892 USA. EM grodzinp@mail.nih.gov NR 12 TC 16 Z9 16 U1 4 U2 27 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0140-6736 EI 1474-547X J9 LANCET JI Lancet PD DEC 20 PY 2014 VL 384 IS 9961 BP 2175 EP 2176 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA AX0QC UT WOS:000346655700006 PM 25625382 ER PT J AU Lee, JH Patel, K Tae, HJ Lustig, A Kim, JW Mattson, MP Taub, DD AF Lee, Jun Ho Patel, Kalpesh Tae, Hyun Jin Lustig, Ana Kim, Jie Wan Mattson, Mark P. Taub, Dennis D. TI Ghrelin augments murine T-cell proliferation by activation of the phosphatidylinositol-3-kinase, extracellular signal-regulated kinase and protein kinase C signaling pathways SO FEBS LETTERS LA English DT Article DE Ghrelin; T-cell; Stress; Glucocorticoid; Proliferation; Signaling; Thymus ID GROWTH-HORMONE RELEASE; PROINFLAMMATORY CYTOKINE EXPRESSION; SMOOTH-MUSCLE-CELLS; CALORIC RESTRICTION; ENDOTHELIAL-CELLS; IMMUNE-SYSTEM; THYMOCYTE HOMEOSTASIS; SECRETAGOGUE RECEPTOR; UNACYLATED GHRELIN; THYMIC INVOLUTION AB Thymic atrophy occurs during normal aging, and is accelerated by exposure to chronic stressors that elevate glucocorticoid levels and impair the naive T cell output. The orexigenic hormone ghrelin was recently shown to attenuate age-associated thymic atrophy. Here, we report that ghrelin enhances the proliferation of murine CD4+ primary T cells and a CD4+ T-cell line. Ghrelin induced activation of the ERK1/2 and Akt signaling pathways, via upstream activation of phosphatidylinositol-3-kinase and protein kinase C, to enhance T-cell proliferation. Moreover, ghrelin induced expression of the cell cycle proteins cyclin D1, cyclin E, cyclin-dependent kinase 2 (CDK2) and retinoblastoma phosphorylation. Finally, ghrelin activated the above-mentioned signaling pathways and stimulated thymocyte proliferation in young and older mice in vivo. Published by Elsevier B.V. on behalf of the Federation of European Biochemical Societies. C1 [Lee, Jun Ho; Patel, Kalpesh; Lustig, Ana; Kim, Jie Wan; Taub, Dennis D.] NIA, Intramural Res Program, Lab Mol Biol & Immunol, Baltimore, MD 21224 USA. [Lee, Jun Ho] Korea Univ, Coll Med, Dept Biochem, Seoul 136701, South Korea. [Lee, Jun Ho] Korea Univ, Coll Med, Div Brain Korea Plus Program Biomed Sci 21, Seoul 136701, South Korea. [Tae, Hyun Jin] NIA, Intramural Res Program, Cardiovasc Sci Lab, Baltimore, MD 21224 USA. [Mattson, Mark P.] NIA, Intramural Res Program, Neurosci Lab, Baltimore, MD 21224 USA. [Taub, Dennis D.] Vet Affairs Med Ctr, Med Serv, Ctr Translat Studies, Washington, DC 20422 USA. RP Mattson, MP (reprint author), NIA, Intramural Res Program, Neurosci Lab, Baltimore, MD 21224 USA. EM mark.mattson@nih.gov; Daniel.Taub@va.gov FU Intramural Research Program of the National Institute on Aging, National Institutes of Health FX We thank Gary Collins and Arnell Carter for technical assistance. This work was supported by the Intramural Research Program of the National Institute on Aging, National Institutes of Health. NR 56 TC 3 Z9 4 U1 5 U2 10 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0014-5793 EI 1873-3468 J9 FEBS LETT JI FEBS Lett. PD DEC 20 PY 2014 VL 588 IS 24 BP 4708 EP 4719 DI 10.1016/j.febslet.2014.10.044 PG 12 WC Biochemistry & Molecular Biology; Biophysics; Cell Biology SC Biochemistry & Molecular Biology; Biophysics; Cell Biology GA AW9KW UT WOS:000346577000025 PM 25447526 ER PT J AU Huang, FZ Zhang, L Long, Z Chen, Z Hou, X Wang, CR Peng, HR Wang, JL Li, JD Duan, RH Xia, K Chuang, DM Tang, BS Jiang, H AF Huang, Fengzhen Zhang, Li Long, Zhe Chen, Zhao Hou, Xuan Wang, Chunrong Peng, Huirong Wang, Junling Li, Jiada Duan, Ranhui Xia, Kun Chuang, De-Maw Tang, Beisha Jiang, Hong TI miR-25 alleviates polyQ-mediated cytotoxicity by silencing ATXN3 SO FEBS LETTERS LA English DT Article DE Spinocerebellar ataxia type 3/Machado-Joseph disease; ATXN3; Cytotoxicity; Neuronal intranuclear inclusion; miR-25; Gene expression regulation ID SPINOCEREBELLAR ATAXIA TYPE-3; MICRORNA EXPRESSION; POLYGLUTAMINE DISEASES; EXPANDED POLYGLUTAMINE; PARKINSONS-DISEASE; ALZHEIMER-DISEASE; HUNTINGTIN-GENE; PROTEIN; NEURODEGENERATION; MODEL AB MicroRNAs (miRNAs) have been reported to play significant roles in the pathogenesis of various polyQ diseases. This study aims to investigate the regulation of ATXN3 gene expression by miRNA. We found that miR-25 reduced both wild-type and polyQ-expanded mutant ataxin-3 protein levels by interacting with the 3'UTR of ATXN3 mRNA. miR-25 also increased cell viability, decreased early apoptosis, and downregulated the accumulation of mutant ataxin-3 protein aggregates in SCA3/MJD cells. These novel results shed light on the potential role of miR-25 in the pathogenesis of SCA3/MJD, and provide a possible therapeutic intervention for this disorder. (C) 2014 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved. C1 [Huang, Fengzhen; Zhang, Li; Long, Zhe; Chen, Zhao; Hou, Xuan; Wang, Chunrong; Peng, Huirong; Wang, Junling; Tang, Beisha; Jiang, Hong] Cent S Univ, Xiangya Hosp, Dept Neurol, Changsha 410008, Hunan, Peoples R China. [Li, Jiada; Duan, Ranhui; Xia, Kun; Tang, Beisha; Jiang, Hong] Cent S Univ, State Key Lab Med Genet China, Changsha 410008, Hunan, Peoples R China. [Tang, Beisha; Jiang, Hong] Cent S Univ, Key Lab Hunan Prov Neurodegenerat Disorders, Changsha 410008, Hunan, Peoples R China. [Huang, Fengzhen] Univ South China, Peoples Hosp Chenzhou 1, Dept Neurol, Chenzhou, Peoples R China. [Huang, Fengzhen] Univ South China, Peoples Hosp Chenzhou 1, Inst Translat Med, Chenzhou, Peoples R China. [Chuang, De-Maw] NIMH, Mol Neurobiol Sect, NIH, Bethesda, MD 20892 USA. RP Jiang, H (reprint author), Cent S Univ, Xiangya Hosp, Dept Neurol, Changsha 410008, Hunan, Peoples R China. EM jianghong73868@126.com FU National Basic Research Program (973 Program) [2012CB944601, 2012CB517902, 2011CB510002]; National Natural Science Foundation of China [81410308019, 81471156, 81271260, 30971585]; Hunan Funds for Distinguished Young Scientists [14JJ1008]; Xinjiang Natural Science Foundation [201318101-4]; High-level medical personnel of Hunan province "225'' Project; Intramural Research Program of the National Institute of Mental Health, National Institutes of Health (IRP-NIMH-NIH); Undergraduate Innovation Project of Central South University [YB13028] FX This study was supported in part by the National Basic Research Program (973 Program) (Nos. 2012CB944601, 2012CB517902 and 2011CB510002 to Hong Jiang), the National Natural Science Foundation of China (Nos. 81410308019, 81471156, 81271260, 30971585 to Hong Jiang), Hunan Funds for Distinguished Young Scientists (No. 14JJ1008 to Hong Jiang), Xinjiang Natural Science Foundation (No. 201318101-4 to Hong Jiang), the Undergraduate Innovation Project of Central South University (No. YB13028 to Hong Jiang), High-level medical personnel of Hunan province "225'' Project, and the Intramural Research Program of the National Institute of Mental Health, National Institutes of Health (IRP-NIMH-NIH). The funders had no further role in study design; in the collection, analysis, or interpretation of data; in the writing of the report; or in the decision to submit the paper for publication. NR 43 TC 2 Z9 2 U1 1 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0014-5793 EI 1873-3468 J9 FEBS LETT JI FEBS Lett. PD DEC 20 PY 2014 VL 588 IS 24 BP 4791 EP 4798 DI 10.1016/j.febslet.2014.11.013 PG 8 WC Biochemistry & Molecular Biology; Biophysics; Cell Biology SC Biochemistry & Molecular Biology; Biophysics; Cell Biology GA AW9KW UT WOS:000346577000035 PM 25451224 ER PT J AU Wei, JT Feng, ZD Partin, AW Brown, E Thompson, I Sokoll, L Chan, DW Lotan, Y Kibel, AS Busby, JE Bidair, M Lin, DW Taneja, SS Viterbo, R Joon, AY Dahlgren, J Kagan, J Srivastava, S Sanda, MG AF Wei, John T. Feng, Ziding Partin, Alan W. Brown, Elissa Thompson, Ian Sokoll, Lori Chan, Daniel W. Lotan, Yair Kibel, Adam S. Busby, J. Erik Bidair, Mohamed Lin, Daniel W. Taneja, Samir S. Viterbo, Rosalia Joon, Aron Y. Dahlgren, Jackie Kagan, Jacob Srivastava, Sudhir Sanda, Martin G. TI Can Urinary PCA3 Supplement PSA in the Early Detection of Prostate Cancer? SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article ID REPEAT BIOPSY; ANTIGEN; ASSAY; MEN; MULTICENTER; SENSITIVITY; TRIAL; PREDICTIVENESS; SPECIFICITY; PERFORMANCE AB Purpose Given the limited sensitivity and specificity of prostate-specific antigen (PSA), its widespread use as a screening tool has raised concerns for the overdiagnosis of low-risk and the underdiagnosis of high-grade prostate cancer. To improve early-detection biopsy decisions, the National Cancer Institute conducted a prospective validation trial to assess the diagnostic performance of the prostate cancer antigen 3 (PCA3) urinary assay for the detection of prostate cancer among men screened with PSA. Patients and Methods In all, 859 men (mean age, 62 years) from 11 centers scheduled for a diagnostic prostate biopsy between December 2009 and June 2011 were enrolled. The primary outcomes were to assess whether PCA3 could improve the positive predictive value (PPV) for an initial biopsy (at a score > 60) and the negative predictive value (NPV) for a repeat biopsy (at a score < 20). Results For the detection of any cancer, PPV was 80% (95% CI, 72% to 86%) in the initial biopsy group, and NPV was 88% (95% CI, 81% to 93%) in the repeat biopsy group. The addition of PCA3 to individual risk estimation models (which included age, race/ethnicity, prior biopsy, PSA, and digital rectal examination) improved the stratification of cancer and of high-grade cancer. Conclusion These data independently support the role of PCA3 in reducing the burden of prostate biopsies among men undergoing a repeat prostate biopsy. For biopsy-naive patients, a high PCA3 score (> 60) significantly increases the probability that an initial prostate biopsy will identify cancer. (C) 2014 by American Society of Clinical Oncology C1 [Wei, John T.] Univ Michigan, Ann Arbor, MI 48109 USA. [Feng, Ziding; Brown, Elissa; Joon, Aron Y.; Dahlgren, Jackie] Fred Hutchinson Canc Res Ctr, Seattle, WA 98109 USA. [Chan, Daniel W.] Univ Washington, Seattle, WA 98195 USA. [Partin, Alan W.; Sokoll, Lori; Chan, Daniel W.] Johns Hopkins Univ, Baltimore, MD USA. [Kagan, Jacob; Srivastava, Sudhir] NCI, Bethesda, MD 20892 USA. [Thompson, Ian] Univ Texas San Antonio, San Antonio, TX USA. [Lotan, Yair] Univ Texas SW Med Ctr Dallas, Dallas, TX 75390 USA. [Kibel, Adam S.] Harvard Univ, Cambridge, MA 02138 USA. [Sanda, Martin G.] Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. [Sanda, Martin G.] Harvard Univ, Sch Med, Boston, MA 02115 USA. [Busby, J. Erik] Univ S Carolina, Greenville, SC USA. [Bidair, Mohamed] San Diego Clin Trials, San Diego, CA USA. [Taneja, Samir S.] NYU, New York, NY USA. [Viterbo, Rosalia] Fox Chase Canc Ctr, Philadelphia, PA 19111 USA. RP Wei, JT (reprint author), Univ Michigan, Dept Urol, 1500 East Med Ctr Dr SPC 5330,3875TC, Ann Arbor, MI 48109 USA. EM jtwei@umich.edu RI Sanda, Martin/B-2023-2015; Wei, John/E-8967-2012 FU [U01-CA-086402]; [U01-CA513913]; [U01-CA96368]; [U24-CA115102] FX Supported by Grants No. U01-CA-086402 (J.T.W.), U01-CA513913 (M.G.S.),U01-CA96368 (Z.F.), and U24-CA115102 (D.W.C.). Some of the reagents for this trial were provided by Gen-Probe. NR 39 TC 42 Z9 43 U1 1 U2 7 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 20 PY 2014 VL 32 IS 36 BP 4066 EP U274 DI 10.1200/JCO.2013.52.8505 PG 8 WC Oncology SC Oncology GA AW4JO UT WOS:000346247500011 PM 25385735 ER PT J AU Palmer, NRA Kent, EE Forsythe, LP Arora, NK Rowland, JH Aziz, NM Blanch-Hartigan, D Oakley-Girvan, I Hamilton, AS Weaver, KE AF Palmer, Nynikka R. A. Kent, Erin E. Forsythe, Laura P. Arora, Neeraj K. Rowland, Julia H. Aziz, Noreen M. Blanch-Hartigan, Danielle Oakley-Girvan, Ingrid Hamilton, Ann S. Weaver, Kathryn E. TI Racial and Ethnic Disparities in Patient-Provider Communication, Quality-of-Care Ratings, and Patient Activation Among Long-Term Cancer Survivors SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article ID BREAST-CANCER; HEALTH-CARE; COLORECTAL-CANCER; PATIENTS PERCEPTIONS; PHYSICIAN COMMUNICATION; CHINESE-AMERICAN; LUNG-CANCER; MEASURE PAM; EXPERIENCES; BEHAVIORS AB Purpose We examined racial and ethnic disparities in patient-provider communication (PPC), perceived care quality, and patient activation among long-term cancer survivors. Methods In 2005 to 2006, survivors of breast, prostate, colorectal, ovarian, and endometrial cancers completed a mailed survey on cancer follow-up care. African American, Asian/Pacific Islander (Asian), Hispanic, and non-Hispanic white (white) survivors who had seen a physician for follow-up care in the past 2 years (n = 1,196) composed the analytic sample. We conducted linear and logistic regression analyses to identify racial and ethnic differences in PPC (overall communication and medical test communication), perceived care quality, and patient activation in clinical care (self-efficacy in medical decisions and perceived control). We further examined the potential contribution of PPC to racial and ethnic differences in perceived care quality and patient activation. Results Compared with white survivors (mean score, 85.16), Hispanic (mean score, 79.95) and Asian (mean score, 76.55) survivors reported poorer overall communication (P = .04 and P < .001, respectively), and Asian survivors (mean score, 79.97) reported poorer medical test communication (P = .001). Asian survivors were less likely to report high care quality (odds ratio, 0.47; 95% CI, 0.30 to 0.72) and reported lower self-efficacy in medical decisions (mean score, 74.71; P < .001) compared with white survivors (mean score, 84.22). No disparity was found in perceived control. PPC was positively associated with care quality (P < .001) and self-efficacy (P < .001). After adjusting for PPC and other covariates, when compared with whites, Asian disparities remained significant. Conclusion Asian survivors report poorer follow-up care communication and care quality. More research is needed to identify contributing factors beyond PPC, such as cultural influences and medical system factors. (C) 2014 by American Society of Clinical Oncology C1 [Palmer, Nynikka R. A.] Univ Calif San Francisco, San Francisco Gen Hosp, San Francisco, CA 94110 USA. [Oakley-Girvan, Ingrid] Canc Prevent Inst Calif, Fremont, CA USA. [Hamilton, Ann S.] Univ So Calif, Keck Sch Med, Los Angeles, CA 90033 USA. [Kent, Erin E.; Arora, Neeraj K.; Rowland, Julia H.; Blanch-Hartigan, Danielle] NCI, NIH, Bethesda, MD 20892 USA. [Aziz, Noreen M.] NINR, NIH, Bethesda, MD 20892 USA. [Forsythe, Laura P.] Patient Ctr Outcomes Res Inst, Washington, DC USA. [Weaver, Kathryn E.] Wake Forest Sch Med, Winston Salem, NC USA. RP Palmer, NRA (reprint author), Univ Calif San Francisco, Dept Med, Div Gen Internal Med, Bldg 10,Ward 13, San Francisco, CA 94110 USA. EM palmern@medsfgh.ucsf.edu OI Palmer, Nynikka/0000-0002-5311-447X FU National Cancer Institute Contracts [N01-PC-35136, N01-PC-35139, HHSN 261201100189P, R25-CA-122061] FX Supported by National Cancer Institute Contracts and Grants No. N01-PC-35136, N01-PC-35139, HHSN 261201100189P, and R25-CA-122061. NR 52 TC 10 Z9 10 U1 4 U2 10 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 20 PY 2014 VL 32 IS 36 BP 4087 EP U304 DI 10.1200/JCO.2014.55.5060 PG 10 WC Oncology SC Oncology GA AW4JO UT WOS:000346247500014 PM 25403220 ER PT J AU Sternberg, CN Apolo, AB AF Sternberg, Cora N. Apolo, Andrea B. TI Neoadjuvant Phase II Studies of Modified Methotrexate, Vinblastine, Doxorubicin, and Cisplatin in Muscle-Invasive Bladder Cancer Reply SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Letter ID CHEMOTHERAPY; TRIAL C1 [Sternberg, Cora N.] Hosp San Camillo Forlanini, Rome, Italy. [Apolo, Andrea B.] NCI, Bethesda, MD 20892 USA. RP Sternberg, CN (reprint author), Hosp San Camillo Forlanini, Rome, Italy. NR 11 TC 0 Z9 0 U1 0 U2 3 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X EI 1527-7755 J9 J CLIN ONCOL JI J. Clin. Oncol. PD DEC 20 PY 2014 VL 32 IS 36 BP 4172 EP 4173 DI 10.1200/JCO.2014.58.5299 PG 2 WC Oncology SC Oncology GA AW4JO UT WOS:000346247500029 PM 25385726 ER PT J AU Gu, JZ Ghosal, S Kleiner, DE AF Gu, Jiezhun Ghosal, Subhashis Kleiner, David E. TI Bayesian ROC curve estimation under verification bias SO STATISTICS IN MEDICINE LA English DT Article DE binormal model; MAR assumption; posterior consistency; ROC curve; verification bias-correction ID DIAGNOSTIC-TESTS; AREA AB Receiver operating characteristic (ROC) curve has been widely used in medical science for its ability to measure the accuracy of diagnostic tests under the gold standard. However, in a complicated medical practice, a gold standard test can be invasive, expensive, and its result may not always be available for all the subjects under study. Thus, a gold standard test is implemented only when it is necessary and possible. This leads to the so-called verification bias', meaning that subjects with verified disease status (also called label) are not selected in a completely random fashion. In this paper, we propose a new Bayesian approach for estimating an ROC curve based on continuous data following the popular semiparametric binormal model in the presence of verification bias. By using a rank-based likelihood, and following Gibbs sampling techniques, we compute the posterior distribution of the binormal parameters intercept and slope, as well as the area under the curve by imputing the missing labels within Markov Chain Monte-Carlo iterations. Consistency of the resulting posterior under mild conditions is also established. We compare the new method with other comparable methods and conclude that our estimator performs well in terms of accuracy. Copyright (c) 2014 John Wiley & Sons, Ltd. C1 [Gu, Jiezhun] Duke Univ, Med Ctr, Duke Clin Res Inst, Durham, NC 27715 USA. [Ghosal, Subhashis] N Carolina State Univ, Dept Stat, Raleigh, NC 27695 USA. [Kleiner, David E.] NCI, Pathol Lab, Bethesda, MD 20892 USA. RP Gu, JZ (reprint author), Duke Univ, Med Ctr, Duke Clin Res Inst, POB 17969, Durham, NC 27715 USA. EM jiezhun.gu@duke.edu FU NSF [DMS-0349111] FX Research of the second author is partially supported by NSF grant number DMS-0349111. NR 22 TC 3 Z9 3 U1 0 U2 6 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0277-6715 EI 1097-0258 J9 STAT MED JI Stat. Med. PD DEC 20 PY 2014 VL 33 IS 29 BP 5081 EP 5096 DI 10.1002/sim.6297 PG 16 WC Mathematical & Computational Biology; Public, Environmental & Occupational Health; Medical Informatics; Medicine, Research & Experimental; Statistics & Probability SC Mathematical & Computational Biology; Public, Environmental & Occupational Health; Medical Informatics; Research & Experimental Medicine; Mathematics GA AT5ZC UT WOS:000345017400004 PM 25269427 ER PT J AU Polley, MYC Polley, EC Huang, EP Freidlin, B Simon, R AF Polley, Mei-Yin C. Polley, Eric C. Huang, Erich P. Freidlin, Boris Simon, Richard TI Two-stage adaptive cutoff design for building and validating a prognostic biomarker signature SO STATISTICS IN MEDICINE LA English DT Article DE cancer biomarker; two-stage design; biomarker validation; cross-validation; early stopping ID NON-HODGKINS-LYMPHOMA; B-CELL LYMPHOMA; ERROR ESTIMATION; CHEMOTHERAPY; SELECTION; MODEL; CHOP AB Cancer biomarkers are frequently evaluated using archived specimens collected from previously conducted therapeutic trials. Routine collection and banking of high quality specimens is an expensive and time-consuming process. Therefore, care should be taken to preserve these precious resources. Here, we propose a novel two-stage adaptive cutoff design that affords the possibility to stop the biomarker study early if an evaluation of the model performance is unsatisfactory at an early stage, thereby allowing one to preserve the remaining specimens for future research. In addition, our design integrates important elements necessary to meet statistical rigor and practical demands for developing and validating a prognostic biomarker signature, including maintaining strict separation between the datasets used to build and evaluate the model and producing a locked-down signature to facilitate future validation. We conduct simulation studies to evaluate the operating characteristics of the proposed design. We show that under the null hypothesis when the model performance is deemed undesirable, the proposed design maintains type I error at the nominal level, has high probabilities of terminating the study early, and results in substantial savings in specimens. Under the alternative hypothesis, power is generally high when the total sample size and the targeted degree of improvement in prediction accuracy are reasonably large. We illustrate the use of the procedure with a dataset in patients with diffuse large-B-cell lymphoma. The practical aspects of the proposed designs are discussed. Published 2014. This article is a U.S. Government work and is in the public domain in the USA. C1 [Polley, Mei-Yin C.; Polley, Eric C.; Huang, Erich P.; Freidlin, Boris; Simon, Richard] NCI, Biometr Res Branch, Bethesda, MD 20892 USA. RP Polley, MYC (reprint author), NCI, Biometr Res Branch, 9609 Med Ctr Dr,Room 5W638,MSC 9735, Bethesda, MD 20892 USA. EM polleymc@mail.nih.gov FU Intramural NIH HHS [Z99 CA999999] NR 18 TC 1 Z9 1 U1 1 U2 6 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0277-6715 EI 1097-0258 J9 STAT MED JI Stat. Med. PD DEC 20 PY 2014 VL 33 IS 29 BP 5097 EP 5110 DI 10.1002/sim.6310 PG 14 WC Mathematical & Computational Biology; Public, Environmental & Occupational Health; Medical Informatics; Medicine, Research & Experimental; Statistics & Probability SC Mathematical & Computational Biology; Public, Environmental & Occupational Health; Medical Informatics; Research & Experimental Medicine; Mathematics GA AT5ZC UT WOS:000345017400005 PM 25263614 ER PT J AU Ali, N Nakhasi, HL Valenzuela, JG Reis, AB AF Ali, Nahid Nakhasi, Hira L. Valenzuela, Jesus G. Reis, Alexandre Barbosa TI largetec immunology for prevention and cure of VL SO FRONTIERS IN IMMUNOLOGY LA English DT Editorial Material DE visceral leishmaniasis; immunotherapy; vaccine; immuno-modulator; Thl response ID HYDROLASE TERMINAL DOMAINS; VISCERAL LEISHMANIASIS; SALIVARY PROTEIN; IMMUNE-RESPONSE; IMMUNOTHERAPY; AMAZONENSIS; PROTECTION; GAMMA C1 [Ali, Nahid] Indian Inst Chem Biol, Infect Dis & Immunol, Kolkata, India. [Nakhasi, Hira L.] US FDA, Silver Spring, MD USA. [Valenzuela, Jesus G.] NIAID, Rockville, MD USA. [Reis, Alexandre Barbosa] Univ Fed Ouro Preto, Ouro Preto, Brazil. RP Ali, N (reprint author), Indian Inst Chem Biol, Infect Dis & Immunol, Kolkata, India. EM nali@iicb.res.in NR 25 TC 1 Z9 1 U1 0 U2 6 PU FRONTIERS RESEARCH FOUNDATION PI LAUSANNE PA PO BOX 110, LAUSANNE, 1015, SWITZERLAND SN 1664-3224 J9 FRONT IMMUNOL JI Front. Immunol. PD DEC 19 PY 2014 VL 5 AR 660 DI 10.3389/fimmu.2014.00660 PG 2 WC Immunology SC Immunology GA CI1YC UT WOS:000354540100001 PM 25566268 ER PT J AU Baez, A Shiloach, J AF Baez, Antonino Shiloach, Joseph TI Effect of elevated oxygen concentration on bacteria, yeasts, and cells propagated for production of biological compounds SO Microbial Cell Factories LA English DT Review DE Hyperoxia; Oxidative stress; ROS; Protein oxidation; SOD activity; Hyperoxygenation ID MITOCHONDRIAL ELECTRON-TRANSPORT; MANGANESE-SUPEROXIDE DISMUTASE; ESCHERICHIA-COLI ACONITASE; AMINO-ACID BIOSYNTHESIS; HUMAN GROWTH-HORMONE; DISSOLVED-OXYGEN; SACCHAROMYCES-CEREVISIAE; RECOMBINANT PROTEIN; HYDROGEN-PEROXIDE; HYPERBARIC-OXYGEN AB The response of bacteria, yeast, and mammalian and insects cells to oxidative stress is a topic that has been studied for many years. However, in most the reported studies, the oxidative stress was caused by challenging the organisms with H2O2 and redox-cycling drugs, but not by subjecting the cells to high concentrations of molecular oxygen. In this review we summarize available information about the effect of elevated oxygen concentrations on the physiology of microorganisms and cells at various culture conditions. In general, increased oxygen concentrations promote higher leakage of reactive oxygen species (superoxide and H2O2) from the respiratory chain affecting metalloenzymes and DNA that in turn cause impaired growth and elevated mutagenesis. To prevent the potential damage, the microorganisms and cells respond by activating antioxidant defenses and repair systems. This review described the factors that affect growth properties and metabolism at elevated oxygen concentrations that cells may be exposed to, in bioreactor sparged with oxygen enriched air which could affect the yield and quality of the recombinant proteins produced by high cell density schemes. C1 [Baez, Antonino; Shiloach, Joseph] NIDDK, Biotechnol Core Lab, NIH, Bethesda, MD 20892 USA. RP Shiloach, J (reprint author), NIDDK, Biotechnol Core Lab, NIH, Bethesda, MD 20892 USA. EM yossi@nih.gov FU National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health FX Funding was provided by the intramural program of the National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health. The authors would like to thank Mrs. D. Livnat for critical editorial assistance. NR 73 TC 3 Z9 3 U1 0 U2 43 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1475-2859 J9 MICROB CELL FACT JI Microb. Cell. Fact. PD DEC 19 PY 2014 VL 13 AR 181 DI 10.1186/s12934-014-0181-5 PG 7 WC Biotechnology & Applied Microbiology SC Biotechnology & Applied Microbiology GA CA6RX UT WOS:000349044300001 PM 25547171 ER PT J AU Choi, YJ Lai, WS Fedic, R Stumpo, DJ Huang, WC Li, LP Perera, L Brewer, BY Wilson, GM Mason, JM Blackshear, PJ AF Choi, Youn-Jeong Lai, Wi S. Fedic, Robert Stumpo, Deborah J. Huang, Weichun Li, Leping Perera, Lalith Brewer, Brandy Y. Wilson, Gerald M. Mason, James M. Blackshear, Perry J. TI The Drosophila Tis11 Protein and Its Effects on mRNA Expression in Flies SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article DE Drosophila; mRNA Decay; Post-transcriptional Regulation; RNA-binding Protein; Zinc Finger; AU-rich Elements; Deadenylation ID ZINC-FINGER PROTEINS; AU-RICH ELEMENT; TRISTETRAPROLIN FAMILY; SCHIZOSACCHAROMYCES-POMBE; GENE-EXPRESSION; FORCE-FIELD; BINDING; DEGRADATION; DEADENYLATION; STABILITY AB Members of the mammalian tristetraprolin family of CCCH tandem zinc finger proteins can bind to certain AU-rich elements (AREs) in mRNAs, leading to their deadenylation and destabilization. Mammals express three or four members of this family, but Drosophila melanogaster and other insects appear to contain a single gene, Tis11. We found that recombinant Drosophila Tis11 protein could bind to ARE-containing RNA oligonucleotides with low nanomolar affinity. Remarkably, co-expression in mammalian cells with target RNAs demonstrated that Tis11 could promote destabilization of ARE-containing mRNAs and that this was partially dependent on a conserved C-terminal sequence resembling the mammalian NOT1 binding domain. Drosophila Tis11 promoted both deadenylation and decay of a target transcript in this heterologous cell system. We used chromosome deletion/duplication and P element insertion to produce two types of Tis11 deficiency in adult flies, both of which were viable and fertile. To address the hypothesis that Tis11 deficiency would lead to the abnormal accumulation of potential target transcripts, we analyzed gene expression in adult flies by deep mRNA sequencing. We identified 69 transcripts from 56 genes that were significantly up-regulated more than 1.5-fold in both types of Tis11-deficient flies. Ten of the up-regulated transcripts encoded probable proteases, but many other functional classes of proteins were represented. Many of the up-regulated transcripts contained potential binding sites for tristetraprolin family member proteins that were conserved in other Drosophila species. Tis11 is thus an ARE-binding, mRNA-destabilizing protein that may play a role in post-transcriptional gene expression in Drosophila and other insects. C1 [Choi, Youn-Jeong; Lai, Wi S.; Stumpo, Deborah J.; Blackshear, Perry J.] NIEHS, Lab Signal Transduct, NIH, Res Triangle Pk, NC 27709 USA. [Fedic, Robert; Mason, James M.] NIEHS, Lab Mol Genet, NIH, Res Triangle Pk, NC 27709 USA. [Huang, Weichun; Li, Leping] NIEHS, Lab Biostat, NIH, Res Triangle Pk, NC 27709 USA. [Perera, Lalith] NIEHS, Struct Biol Lab, NIH, Res Triangle Pk, NC 27709 USA. [Brewer, Brandy Y.; Wilson, Gerald M.] Univ Maryland, Dept Biochem & Mol Biol, Baltimore, MD 21201 USA. [Blackshear, Perry J.] Duke Univ, Med Ctr, Dept Med, Durham, NC 27710 USA. [Blackshear, Perry J.] Duke Univ, Med Ctr, Dept Biochem, Durham, NC 27710 USA. RP Blackshear, PJ (reprint author), NIEHS, NIH, 111 Alexander Dr,F1-13, Res Triangle Pk, NC 27709 USA. EM black009@niehs.nih.gov FU National Institutes of Health (NIH), NIEHS, Intramural Research Program; NIH [R01 CA102428]; Oliver Smithies Visiting Professorship at Balliol College, Oxford FX This work was supported, in whole or in part, by the National Institutes of Health (NIH), NIEHS, Intramural Research Program and by NIH Grant R01 CA102428 (to G. M. W.). This work was also supported by an Oliver Smithies Visiting Professorship at Balliol College, Oxford (to P. J. B.). NR 60 TC 3 Z9 3 U1 2 U2 10 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 EI 1083-351X J9 J BIOL CHEM JI J. Biol. Chem. PD DEC 19 PY 2014 VL 289 IS 51 BP 35042 EP 35060 DI 10.1074/jbc.M114.593491 PG 19 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA AX0RT UT WOS:000346660200001 PM 25342740 ER PT J AU Park, SY Waheed, AA Zhang, ZR Freed, EO Bonifacino, JS AF Park, Sang Yoon Waheed, Abdul A. Zhang, Zai-Rong Freed, Eric O. Bonifacino, Juan S. TI HIV-1 Vpu Accessory Protein Induces Caspase-mediated Cleavage of IRF3 Transcription Factor SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article DE Apoptosis; Caspase; Cellular Immune Response; Human Immunodeficiency Virus (HIV); Innate Immunity; Vpu; Interferon Regulatory Factor 3 ID INTERFERON REGULATORY FACTOR-3; VIRUS TYPE-1 NEF; CD4(+) T-CELLS; BETA-TRCP; KAPPA-B; ANTIVIRAL RESPONSE; DENDRITIC CELLS; RESTRICTS HIV-1; DOWN-REGULATION; INFECTED-CELLS AB Vpu is an accessory protein encoded by HIV-1 that interferes with multiple host-cell functions. Herein we report that expression of Vpu by transfection into 293T cells causes partial proteolytic cleavage of interferon regulatory factor 3 (IRF3), a key transcription factor in the innate anti-viral response. Vpu-induced IRF3 cleavage is mediated by caspases and occurs mainly at Asp-121. Cleavage produces a C-terminal fragment of approximate to 37 kDa that comprises the IRF dimerization and transactivation domains but lacks the DNA-binding domain. A similar cleavage is observed upon infection of the Jurkat T-cell line with vesicular stomatitis virus G glycoprotein (VSV-G)-pseudotyped HIV-1. Two other HIV-1 accessory proteins, Vif and Vpr, also contribute to the induction of IRF3 cleavage in both the transfection and the infection systems. The C-terminal IRF3 fragment interferes with the transcriptional activity of full-length IRF3. Cleavage of IRF3 under all of these conditions correlates with cleavage of poly(ADP-ribose) polymerase, an indicator of apoptosis. We conclude that Vpu contributes to the attenuation of the anti-viral response by partial inactivation of IRF3 while host cells undergo apoptosis. C1 [Park, Sang Yoon; Zhang, Zai-Rong; Bonifacino, Juan S.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Cell Biol & Metab Program, NIH, Bethesda, MD 20892 USA. [Waheed, Abdul A.; Freed, Eric O.] NCI, HIV Drug Resistance Program, Ctr Canc Res, NIH, Frederick, MD 21702 USA. RP Bonifacino, JS (reprint author), Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Cell Biol & Metab Program, NIH, Bethesda, MD 20892 USA. EM bonifacinoj@helix.nih.gov OI Bonifacino, Juan S./0000-0002-5673-6370 FU NICHD; NCI; Intramural AIDS Targeted Antiviral Program (IATAP), National Institutes of Health; National Institutes of Health [IATAP-ZIA HD008909, NICHD DIR-ZIA HD001607] FX This work was funded by the Intramural Programs of the NICHD and NCI and the Intramural AIDS Targeted Antiviral Program (IATAP), National Institutes of Health, and by National Institutes of Health Grants IATAP-ZIA HD008909 and NICHD DIR-ZIA HD001607 (to J. S. B.). NR 43 TC 6 Z9 6 U1 0 U2 3 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 EI 1083-351X J9 J BIOL CHEM JI J. Biol. Chem. PD DEC 19 PY 2014 VL 289 IS 51 BP 35102 EP 35110 DI 10.1074/jbc.M114.597062 PG 9 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA AX0RT UT WOS:000346660200005 PM 25352594 ER PT J AU Rout, AK Strub, MP Piszczek, G Tjandra, N AF Rout, Ashok K. Strub, Marie-Paule Piszczek, Grzegorz Tjandra, Nico TI Structure of Transmembrane Domain of Lysosome-associated Membrane Protein Type 2a (LAMP-2A) Reveals Key Features for Substrate Specificity in Chaperone-mediated Autophagy SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article DE Autophagy; Chaperone; Nuclear Magnetic Resonance (NMR); Protein Structure; Transport; CMA; DPC; LAMP-2; Micelles ID TRIPLE-RESONANCE NMR; CYTOSOLIC PROTEINS; ALPHA-SYNUCLEIN; RAT-LIVER; BACKBONE DYNAMICS; RIBONUCLEASE-A; MUTANT UCH-L1; DISEASE; DEGRADATION; MACROAUTOPHAGY AB Chaperone-mediated autophagy (CMA) is a highly regulated cellular process that mediates the degradation of a selective subset of cytosolic proteins in lysosomes. Increasing CMA activity is one way for a cell to respond to stress, and it leads to enhanced turnover of non-critical cytosolic proteins into sources of energy or clearance of unwanted or damaged proteins from the cytosol. The lysosome-associated membrane protein type 2a (LAMP-2A) together with a complex of chaperones and co-chaperones are key regulators of CMA. LAMP-2A is a transmembrane protein component for protein translocation to the lysosome. Here we present a study of the structure and dynamics of the transmembrane domain of human LAMP-2A in n-dodecylphosphocholine micelles by nuclear magnetic resonance (NMR). We showed that LAMP-2A exists as a homotrimer in which the membrane-spanning helices wrap around each other to form a parallel coiled coil conformation, whereas its cytosolic tail is flexible and exposed to the cytosol. This cytosolic tail of LAMP-2A interacts with chaperone Hsc70 and a CMA substrate RNase A with comparable affinity but not with Hsp40 and RNase S peptide. Because the substrates and the chaperone complex can bind at the same time, thus creating a bimodal interaction, we propose that substrate recognition by chaperones and targeting to the lysosomal membrane by LAMP-2A are coupled. This can increase substrate affinity and specificity as well as prevent substrate aggregation, assist in the unfolding of the substrate, and promote the formation of the higher order complex of LAMP-2A required for translocation. C1 [Rout, Ashok K.; Strub, Marie-Paule; Tjandra, Nico] NHLBI, Lab Mol Biophys, NIH, Bethesda, MD 20892 USA. [Piszczek, Grzegorz] NHLBI, Biophys Core, Biochem & Biophys Ctr, NIH, Bethesda, MD 20892 USA. RP Tjandra, N (reprint author), NHLBI, Lab Mol Biophys, NIH, Bldg 10, Bethesda, MD 20892 USA. EM tjandran@nhlbi.nih.gov FU Intramural Research Program of the National Institutes of Health, NHLBI FX This work was supported by the Intramural Research Program of the National Institutes of Health, NHLBI. NR 81 TC 12 Z9 14 U1 5 U2 17 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 EI 1083-351X J9 J BIOL CHEM JI J. Biol. Chem. PD DEC 19 PY 2014 VL 289 IS 51 BP 35111 EP 35123 DI 10.1074/jbc.M114.609446 PG 13 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA AX0RT UT WOS:000346660200006 PM 25342746 ER PT J AU Diner, I Hales, CM Bishof, I Rabenold, L Duong, DM Yi, H Laur, O Gearing, M Troncoso, J Thambisetty, M Lah, JJ Levey, AI Seyfried, NT AF Diner, Ian Hales, Chadwick M. Bishof, Isaac Rabenold, Lake Duong, Duc M. Yi, Hong Laur, Oskar Gearing, Marla Troncoso, Juan Thambisetty, Madhav Lah, James J. Levey, Allan I. Seyfried, Nicholas T. TI Aggregation Properties of the Small Nuclear Ribonucleoprotein U1-70K in Alzheimer Disease SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article DE Neurodegenerative Disease; Protein Aggregation; RNA; Spliceosome; Tau Protein (Tau) ID FRONTOTEMPORAL LOBAR DEGENERATION; AMYOTROPHIC-LATERAL-SCLEROSIS; CELL-FREE FORMATION; PRION-LIKE DOMAINS; NEURODEGENERATIVE DISEASE; PROTEIN AGGREGATION; CORTICOBASAL DEGENERATION; TDP-43; GRANULES; PHOSPHORYLATION AB Recent evidence indicates that U1-70K and other U1 small nuclear ribonucleoproteins are Sarkosyl-insoluble and associate with Tau neurofibrillary tangles selectively in Alzheimer disease (AD). Currently, the mechanisms underlying the conversion of soluble nuclear U1 small nuclear ribonucleoproteins into insoluble cytoplasmic aggregates remain elusive. Based on the biochemical and subcellular distribution properties of U1-70K in AD, we hypothesized that aggregated U1-70K itself or other biopolymers (e.g. proteins or nucleic acids) interact with and sequester natively folded soluble U1-70K into insoluble aggregates. Here, we demonstrate that total homogenates from AD brain induce soluble U1-70K from control brain or recombinant U1-70K to become Sarkosyl-insoluble. This effect was not dependent on RNA and did not correlate with detergent-insoluble Tau levels as AD homogenates with reduced levels of these components were still capable of inducing U1-70K aggregation. In contrast, proteinase K-treated AD homogenates and Sarkosyl-soluble AD fractions were unable to induce U1-70K aggregation, indicating that aggregated proteins in AD brain are responsible for inducing soluble U1-70K aggregation. It was determined that the C terminus of U1-70K, which harbors two disordered low complexity (LC) domains, is necessary for U1-70K aggregation. Moreover, both LC1 and LC2 domains were sufficient for aggregation. Finally, protein cross-linking and mass spectrometry studies demonstrated that a U1-70K fragment harboring the LC1 domain directly interacts with aggregated U1-70K in AD brain. Our results support a hypothesis that aberrant forms of U1-70K in AD can directly sequester soluble forms of U1-70K into insoluble aggregates. C1 [Diner, Ian; Bishof, Isaac; Rabenold, Lake; Duong, Duc M.; Seyfried, Nicholas T.] Emory Univ, Dept Biochem, Atlanta, GA 30322 USA. [Hales, Chadwick M.; Lah, James J.; Levey, Allan I.; Seyfried, Nicholas T.] Emory Univ, Dept Neurol, Atlanta, GA 30322 USA. [Yi, Hong] Emory Univ, Robert P Apkarian Integrated Electron Microscopy, Atlanta, GA 30322 USA. [Laur, Oskar] Emory Univ, Div Microbiol, Atlanta, GA 30322 USA. [Laur, Oskar] Emory Univ, Yerkes Res Ctr, Atlanta, GA 30322 USA. [Gearing, Marla] Johns Hopkins Sch Med, Dept Expt Pathol, Baltimore, MD 21205 USA. [Troncoso, Juan] Johns Hopkins Sch Med, Dept Pathol & Neurol, Baltimore, MD 21205 USA. [Thambisetty, Madhav] NIA, NIH, Baltimore, MD 21224 USA. [Diner, Ian; Hales, Chadwick M.; Bishof, Isaac; Rabenold, Lake; Duong, Duc M.; Gearing, Marla; Lah, James J.; Levey, Allan I.; Seyfried, Nicholas T.] Ctr Neurodegenerat Dis, Atlanta, GA 30322 USA. [Diner, Ian; Hales, Chadwick M.; Bishof, Isaac; Rabenold, Lake; Duong, Duc M.; Yi, Hong; Laur, Oskar; Gearing, Marla; Lah, James J.; Levey, Allan I.; Seyfried, Nicholas T.] Emory Univ, Sch Med, Atlanta, GA 30322 USA. RP Seyfried, NT (reprint author), Emory Univ, Sch Med, Dept Biochem, 1510 Clifton Rd, Atlanta, GA 30322 USA. EM nseyfri@emory.edu FU National Institutes of Health [P50AG025688, P30NS055077, 5T32GM008367]; National Institutes of Health Intramural Research Program; National Institute on Aging; Alzheimer's Association New Investigator Research Award [NIRG-12-242297] FX This work was supported, in whole or in part, by National Institutes of Health Grant P50AG025688 (to the Emory Alzheimer's Disease Center) and Grant P30NS055077 (to the Emory Neuroscience NINDS Core Facilities), the National Institutes of Health Intramural Research Program, and the National Institute on Aging. This work was also supported by Alzheimer's Association New Investigator Research Award NIRG-12-242297 (to N. T. S.).; Supported by National Institutes of Health Grant 5T32GM008367. NR 49 TC 4 Z9 4 U1 0 U2 4 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 EI 1083-351X J9 J BIOL CHEM JI J. Biol. Chem. PD DEC 19 PY 2014 VL 289 IS 51 BP 35296 EP 35313 DI 10.1074/jbc.M114.562959 PG 18 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA AX0RT UT WOS:000346660200022 PM 25355317 ER PT J AU Lorsch, JR Collins, FS Lippincott-Schwartz, J AF Lorsch, Jon R. Collins, Francis S. Lippincott-Schwartz, Jennifer TI Fixing problems with cell lines SO SCIENCE LA English DT Editorial Material ID REPRODUCIBILITY C1 [Lorsch, Jon R.] NIGMS, Bethesda, MD 20892 USA. [Collins, Francis S.] NIH, Bethesda, MD 20892 USA. [Lippincott-Schwartz, Jennifer] Amer Soc Cell Biol, Bethesda, MD 20814 USA. [Lippincott-Schwartz, Jennifer] NICHHD, Bethesda, MD 20892 USA. RP Lorsch, JR (reprint author), NIGMS, Bethesda, MD 20892 USA. EM jon.lorsch@nih.gov OI Lorsch, Jon/0000-0002-4521-4999 NR 13 TC 22 Z9 24 U1 5 U2 18 PU AMER ASSOC ADVANCEMENT SCIENCE PI WASHINGTON PA 1200 NEW YORK AVE, NW, WASHINGTON, DC 20005 USA SN 0036-8075 EI 1095-9203 J9 SCIENCE JI Science PD DEC 19 PY 2014 VL 346 IS 6216 BP 1452 EP 1453 DI 10.1126/science.1259110 PG 2 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA AW8UI UT WOS:000346536500034 PM 25525228 ER PT J AU Briggs, JP AF Briggs, Josephine P. TI A global scientific challenge: Learning the right lessons from ancient healing practices SO SCIENCE LA English DT Article ID ACUPUNCTURE C1 NIH, Natl Ctr Complementary & Alternat Med, Bethesda, MD 20892 USA. RP Briggs, JP (reprint author), NIH, Natl Ctr Complementary & Alternat Med, Bldg 10, Bethesda, MD 20892 USA. EM briggsj@mail.nih.gov NR 10 TC 0 Z9 0 U1 0 U2 9 PU AMER ASSOC ADVANCEMENT SCIENCE PI WASHINGTON PA 1200 NEW YORK AVE, NW, WASHINGTON, DC 20005 USA SN 0036-8075 EI 1095-9203 J9 SCIENCE JI Science PD DEC 19 PY 2014 VL 346 IS 6216 BP S7 EP S9 PG 3 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA AW8UI UT WOS:000346536500005 ER PT J AU Fan, TP Briggs, J Liu, L Lu, A van der Greef, J Xu, A AF Fan, Tai-Ping Briggs, Josephine Liu, Liang Lu, Aiping Van der Greef, Jan Xu, Anlong TI Integrating traditional medicine into modern health care SO SCIENCE LA English DT Editorial Material C1 [Fan, Tai-Ping] Univ Cambridge, Cambridge CB2 1TN, England. [Briggs, Josephine] NIH, Natl Ctr Complementary & Alternat Med, Hyattsville, MD USA. [Liu, Liang] Macau Univ Sci & Technol, Macau Sar, Peoples R China. [Lu, Aiping] Hong Kong Baptist Univ, Hong Kong, Hong Kong, Peoples R China. [Van der Greef, Jan] Leiden Univ, NL-2300 RA Leiden, Netherlands. [Van der Greef, Jan] TNO, Delft, Netherlands. [Xu, Anlong] Beijing Univ Chinese Med, Beijing, Peoples R China. RP Fan, TP (reprint author), Univ Cambridge, Cambridge CB2 1TN, England. NR 0 TC 0 Z9 0 U1 1 U2 15 PU AMER ASSOC ADVANCEMENT SCIENCE PI WASHINGTON PA 1200 NEW YORK AVE, NW, WASHINGTON, DC 20005 USA SN 0036-8075 EI 1095-9203 J9 SCIENCE JI Science PD DEC 19 PY 2014 VL 346 IS 6216 BP S4 EP S4 PG 1 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA AW8UI UT WOS:000346536500003 ER PT J AU Ishwaran, H Malley, JD AF Ishwaran, Hemant Malley, James D. TI Synthetic learning machines SO BIODATA MINING LA English DT Article DE Machine; Nodesize; Random forest; Trees; Synthetic feature ID RANDOM FORESTS AB Background: Using a collection of different terminal nodesize constructed random forests, each generating a synthetic feature, a synthetic random forest is defined as a kind of hyperforest, calculated using the new input synthetic features, along with the original features. Results: Using a large collection of regression and multiclass datasets we show that synthetic random forests outperforms both conventional random forests and the optimized forest from the regresssion portfolio. Conclusions: Synthetic forests removes the need for tuning random forests with no additional effort on the part of the researcher. Importantly, the synthetic forest does this with evidently no loss in prediction compared to a well-optimized single random forest. C1 [Ishwaran, Hemant] Univ Miami, Div Biostat, Miami, FL 33136 USA. [Malley, James D.] NIH, Ctr Informat Technol, Bethesda, MD 20892 USA. RP Ishwaran, H (reprint author), Univ Miami, Div Biostat, 1120 NW 14th St, Miami, FL 33136 USA. EM hemant.ishwaran@gmail.com FU National Science Foundation [1148991]; National Cancer Institute [R01CA163739]; Intramural Research Program at the National Institutes of Health FX HI was funded by DMS grant 1148991 from the National Science Foundation and grant R01CA163739 from the National Cancer Institute. JDM was supported by the Intramural Research Program at the National Institutes of Health. The authors thank the referee of the paper for their wonderfully helpful comments. NR 15 TC 1 Z9 1 U1 2 U2 2 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1756-0381 J9 BIODATA MIN JI BioData Min. PD DEC 18 PY 2014 VL 7 AR 28 DI 10.1186/s13040-014-0028-y PG 12 WC Mathematical & Computational Biology SC Mathematical & Computational Biology GA CB6AY UT WOS:000349710400001 PM 25614764 ER PT J AU Qian, J Wang, Q Dose, M Pruett, N Kieffer-Kwon, KR Resch, W Liang, GQ Tang, ZH Mathe, E Benner, C Dubois, W Nelson, S Vian, L Oliveira, TY Jankovic, M Hakim, O Gazumyan, A Pavri, R Awasthi, P Song, B Liu, G Chen, LY Zhu, SD Feigenbaum, L Staudt, L Murre, C Ruan, YJ Robbiani, DF Pan-Hammarstrom, Q Nussenzweig, MC Casellas, R AF Qian, Jason Wang, Qiao Dose, Marei Pruett, Nathanael Kieffer-Kwon, Kyong-Rim Resch, Wolfgang Liang, Genqing Tang, Zhonghui Mathe, Ewy Benner, Christopher Dubois, Wendy Nelson, Steevenson Vian, Laura Oliveira, Thiago Y. Jankovic, Mila Hakim, Ofir Gazumyan, Anna Pavri, Rushad Awasthi, Parirokh Song, Bin Liu, Geng Chen, Longyun Zhu, Shida Feigenbaum, Lionel Staudt, Louis Murre, Cornelis Ruan, Yijun Robbiani, Davide F. Pan-Hammarstrom, Qiang Nussenzweig, Michel C. Casellas, Rafael TI B Cell Super-Enhancers and Regulatory Clusters Recruit AID Tumorigenic Activity SO CELL LA English DT Article ID INDUCED CYTIDINE DEAMINASE; RNA-POLYMERASE-II; RECURRENT CHROMOSOMAL TRANSLOCATIONS; CLASS SWITCH RECOMBINATION; HEAVY-CHAIN LOCUS; SOMATIC HYPERMUTATION; MUTATIONAL PROCESSES; GENOMIC INSTABILITY; SEQUENCING REVEALS; IG GENES AB The antibody gene mutator activation-induced cytidine deaminase (AID) promiscuously damages oncogenes, leading to chromosomal translocations and tumorigenesis. Why nonimmunoglobulin loci are susceptible to AID activity is unknown. Here, we study AID-mediated lesions in the context of nuclear architecture and the B cell regulome. We show that AID targets are not randomly distributed across the genome but are predominantly grouped within super-enhancers and regulatory clusters. Unexpectedly, in these domains, AID deaminates active promoters and eRNA(+) enhancers interconnected in some instances over megabases of linear chromatin. Using genome editing, we demonstrate that 3D-linked targets cooperate to recruit AID-mediated breaks. Furthermore, a comparison of hypermutation in mouse B cells, AID-induced kataegis in human lymphomas, and translocations in MEFs reveals that AID damages different genes in different cell types. Yet, in all cases, the targets are predominantly associated with topological complex, highly transcribed super-enhancers, demonstrating that these compartments are key mediators of AID recruitment. C1 [Qian, Jason; Dose, Marei; Pruett, Nathanael; Kieffer-Kwon, Kyong-Rim; Resch, Wolfgang; Liang, Genqing; Mathe, Ewy; Nelson, Steevenson; Vian, Laura; Casellas, Rafael] NIAMS, NIH, Bethesda, MD 20892 USA. [Wang, Qiao; Oliveira, Thiago Y.; Jankovic, Mila; Gazumyan, Anna; Robbiani, Davide F.; Nussenzweig, Michel C.] Rockefeller Univ, Lab Mol Immunol, New York, NY 10065 USA. [Tang, Zhonghui; Ruan, Yijun] Univ Connecticut, Jackson Lab Genom Med, Dept Genet & Dev Biol, Farmington, CT 06030 USA. [Murre, Cornelis] Univ Calif San Diego, Div Biol Sci, Dept Mol Biol, La Jolla, CA 92093 USA. [Dubois, Wendy; Casellas, Rafael] NCI, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. [Hakim, Ofir] Bar Ilan Univ, IL-5290002 Ramat Gan, Israel. [Pavri, Rushad] Vienna BioCtr, IMP, A-1030 Vienna, Austria. [Awasthi, Parirokh; Feigenbaum, Lionel] Sci Applicat Int Corp Frederick, NCI Frederick Canc Res & Dev Ctr, Frederick, MD 21702 USA. [Song, Bin; Liu, Geng; Chen, Longyun; Zhu, Shida] Beijing Genom Inst, Shenzhen 518083, Peoples R China. [Staudt, Louis] NCI, Metab Branch, NIH, Bethesda, MD 20892 USA. [Pan-Hammarstrom, Qiang] Karolinska Inst, Karolinska Univ Hosp, Dept Lab Med, S-14186 Stockholm, Sweden. [Nussenzweig, Michel C.] Rockefeller Univ, HHMI, New York, NY 10065 USA. [Benner, Christopher] Salk Inst Biol Studies, Integrat Genom & Bioinformat Core, La Jolla, CA 92037 USA. RP Dose, M (reprint author), NIAMS, NIH, Bethesda, MD 20892 USA. EM marei.dose@nih.gov; rafael.casellas@nih.gov OI Dose, Marei/0000-0001-5394-9779 FU Intramural Research Programs of the National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS); National Cancer Institute (NCI); Jackson Laboratory fund [JAX19020120]; European Research Council (ERC) [242551-ImmunoSwitch]; NIH grant [AI037526] FX We thank Daniel Hodson for isolating GC B cells, Ethan Tyler for designing Figure S7B, Gustavo Gutierrez for technical assistance with deep-sequencing, David Bosque and Tom Eisenreich for managing the mouse colonies, and Jim Simone, Klara Velinzon, and Yelena Shatalina for FACS sorting. This work was supported by the Intramural Research Programs of the National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS) and the National Cancer Institute (NCI), the Jackson Laboratory fund (JAX19020120), the European Research Council (ERC) (242551-ImmunoSwitch), and NIH grant AI037526 to M.C.N. M.C.N. is a Howard Hughes Medical Institute (HHMI) Investigator. Animal experiments were performed according to NIH and Rockefeller approved protocols. This study used the high-performance computational capabilities of NIH Helix Systems (http://helix.nih.gov). NR 57 TC 60 Z9 61 U1 3 U2 24 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 0092-8674 EI 1097-4172 J9 CELL JI Cell PD DEC 18 PY 2014 VL 159 IS 7 BP 1524 EP 1537 DI 10.1016/j.cell.2014.11.013 PG 14 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA AZ0FW UT WOS:000347922500008 PM 25483777 ER PT J AU Meng, FL Du, Z Federation, A Hu, JZ Wang, Q Kieffer-Kwon, KR Meyers, RM Amor, C Wasserman, CR Neuberg, D Casellas, R Nussenzweig, MC Bradner, JE Liu, XS Alt, FW AF Meng, Fei-Long Du, Zhou Federation, Alexander Hu, Jiazhi Wang, Qiao Kieffer-Kwon, Kyong-Rim Meyers, Robin M. Amor, Corina Wasserman, Caitlyn R. Neuberg, Donna Casellas, Rafael Nussenzweig, Michel C. Bradner, James E. Liu, X. Shirley Alt, Frederick W. TI Convergent Transcription at Intragenic Super-Enhancers Targets AID-Initiated Genomic Instability SO CELL LA English DT Article ID RNA-POLYMERASE-II; INDUCED CYTIDINE DEAMINASE; CLASS-SWITCH RECOMBINATION; B-CELL LYMPHOMA; SOMATIC HYPERMUTATION; SEQUENCING REVEALS; CHROMOSOMAL TRANSLOCATIONS; NONCODING TRANSCRIPTION; IG GENES; C-MYC AB Activation-induced cytidine deaminase (AID) initiates both somatic hypermutation (SHM) for antibody affinity maturation and DNA breakage for antibody class switch recombination (CSR) via transcription-dependent cytidine deamination of single-stranded DNA targets. Though largely specific for immunoglobulin genes, AID also acts on a limited set of off-targets, generating oncogenic translocations and mutations that contribute to B cell lymphoma. How AID is recruited to off-targets has been a long-standing mystery. Based on deep GRO-seq studies of mouse and human B lineage cells activated for CSR or SHM, we report that most robust AID off-target translocations occur within highly focal regions of target genes in which sense and antisense transcription converge. Moreover, we found that such AID-targeting "convergent'' transcription arises from antisense transcription that emanates from super-enhancers within sense transcribed gene bodies. Our findings provide an explanation for AID off-targeting to a small subset of mostly lineage-specific genes in activated B cells. C1 [Meng, Fei-Long; Du, Zhou; Hu, Jiazhi; Meyers, Robin M.; Amor, Corina; Wasserman, Caitlyn R.; Alt, Frederick W.] Harvard Univ, Boston Childrens Hosp, Howard Hughes Med Inst, Program Cellular & Mol Med,Med Sch, Boston, MA 02115 USA. [Meng, Fei-Long; Du, Zhou; Hu, Jiazhi; Meyers, Robin M.; Amor, Corina; Wasserman, Caitlyn R.; Alt, Frederick W.] Harvard Univ, Sch Med, Dept Genet, Boston, MA 02115 USA. [Du, Zhou] Tongji Univ, Sch Life Sci & Technol, Dept Bioinformat, Shanghai 200092, Peoples R China. [Federation, Alexander; Bradner, James E.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Federation, Alexander; Bradner, James E.] Harvard Univ, Sch Med, Dept Med, Boston, MA 02115 USA. [Wang, Qiao; Nussenzweig, Michel C.] Rockefeller Univ, Howard Hughes Med Inst, Lab Mol Immunol, New York, NY 10065 USA. [Kieffer-Kwon, Kyong-Rim; Casellas, Rafael] NCI, NIAMS, NIH, Bethesda, MD 20892 USA. [Kieffer-Kwon, Kyong-Rim; Casellas, Rafael] NCI, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. [Neuberg, Donna; Liu, X. Shirley] Dana Farber Canc Inst, Dept Biostat & Computat Biol, Boston, MA 02115 USA. [Neuberg, Donna; Liu, X. Shirley] Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA. RP Bradner, JE (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Med Oncol, 44 Binney St, Boston, MA 02115 USA. EM james_bradner@dfci.harvard.edu; alt@enders.tch.harvard.edu FU NIH grants [R01AI077595, P01CA109901]; Leukemia and Lymphoma Society (LLS) SCOR grant; NIH grant [1R01GM099409]; Leukemia and Lymphoma Society SCOR; National Science Foundation; NIH [1R01 CA176745-01, P01 CA109901, AI072529, AI037526]; intramural research program of NIAMS, NIH; Robertson Foundation/Cancer Research Institute Irvington Fellowship; National Science Foundation of China [NSFC 31329003] FX F.W.A was supported by NIH grants R01AI077595 and P01CA109901, and a Leukemia and Lymphoma Society (LLS) SCOR grant, and he is an investigator of the Howard Hughes Medical Institute. X.S.L was supported by NIH grant 1R01GM099409. A.F. and J.E.B. were supported by a Leukemia and Lymphoma Society SCOR, the National Science Foundation, and NIH grants 1R01 CA176745-01 and P01 CA109901. M.C.N. was supported by NIH grants AI072529 and AI037526 and is an investigator of the Howard Hughes Medical Institute. K.K. and R.C. were supported by the intramural research program of NIAMS, NIH. F.L.M. is a Lymphoma Research Foundation postdoctoral fellow and was a Cancer Research Institute postdoctoral fellow. J.Z. is supported by a Robertson Foundation/Cancer Research Institute Irvington Fellowship. Z.D. was supported by the National Science Foundation of China grant NSFC 31329003. The authors thank Drs. Yi Zhang and Li Shen for assistance with DNA sequencing and Dr. David Schatz (Yale University) for providing primers for GC SHM targets. Dr. Bradner is a scientific founder of Syros Pharmaceuticals, which is developing drugs targeting super-enhancers. NR 53 TC 55 Z9 56 U1 2 U2 18 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 0092-8674 EI 1097-4172 J9 CELL JI Cell PD DEC 18 PY 2014 VL 159 IS 7 BP 1538 EP 1548 DI 10.1016/j.cell.2014.11.014 PG 11 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA AZ0FW UT WOS:000347922500009 PM 25483776 ER PT J AU Lu, W Zhang, Y McDonald, DO Jing, HE Carroll, B Robertson, N Zhang, Q Griffin, H Sanderson, S Lakey, JH Morgan, NV Reynard, LN Zheng, L Murdock, HM Turvey, SE Hackett, SJ Prestidge, T Hall, JM Cant, AJ Matthews, HF Koref, MFS Simon, AK Korolchuk, VI Lenardo, MJ Hambleton, S Su, HC AF Lu, Wei Zhang, Yu McDonald, David O. Jing, Huie Carroll, Bernadette Robertson, Nic Zhang, Qian Griffin, Helen Sanderson, Sharon Lakey, Jeremy H. Morgan, Neil V. Reynard, Louise N. Zheng, Lixin Murdock, Heardley M. Turvey, Stuart E. Hackett, Scott J. Prestidge, Tim Hall, Julie M. Cant, Andrew J. Matthews, Helen F. Koref, Mauro F. Santibanez Simon, Anna Katharina Korolchuk, Viktor I. Lenardo, Michael J. Hambleton, Sophie Su, Helen C. TI Dual Proteolytic Pathways Govern Glycolysis and Immune Competence SO CELL LA English DT Article ID TRIPEPTIDYL PEPTIDASE-II; CHAPERONE-MEDIATED AUTOPHAGY; CELL-ACTIVATION; AEROBIC GLYCOLYSIS; GENE-EXPRESSION; T-LYMPHOCYTES; HEXOKINASE 2; HUMAN BRAIN; DEGRADATION; GLUCOSE AB Proteasomes and lysosomes constitute the major cellular systems that catabolize proteins to recycle free amino acids for energy and new protein synthesis. Tripeptidyl peptidase II (TPPII) is a large cytosolic proteolytic complex that functions in tandem with the proteasome-ubiquitin protein degradation pathway. We found that autosomal recessive TPP2 mutations cause recurrent infections, autoimmunity, and neurodevelopmental delay in humans. We show that a major function of TPPII in mammalian cells is to maintain amino acid levels and that TPPII-deficient cells compensate by increasing lysosome number and proteolytic activity. However, the overabundant lysosomes derange cellular metabolism by consuming the key glycolytic enzyme hexokinase-2 through chaperone-mediated autophagy. This reduces glycolysis and impairs the production of effector cytokines, including IFN-gamma and IL-1 beta. Thus, TPPII controls the balance between intracellular amino acid availability, lysosome number, and glycolysis, which is vital for adaptive and innate immunity and neurodevelopmental health. C1 [Lu, Wei; Zheng, Lixin; Matthews, Helen F.; Lenardo, Michael J.] NIAID, Immunol Lab, NIH, Bethesda, MD 20892 USA. [Lu, Wei; Zhang, Yu; Jing, Huie; Zhang, Qian; Zheng, Lixin; Murdock, Heardley M.; Matthews, Helen F.; Lenardo, Michael J.; Su, Helen C.] NIAID, Clin Genom Program, NIH, Bethesda, MD 20892 USA. [Zhang, Yu; Jing, Huie; Zhang, Qian; Murdock, Heardley M.; Su, Helen C.] NIAID, Lab Host Def, NIH, Bethesda, MD 20892 USA. [McDonald, David O.; Robertson, Nic; Reynard, Louise N.; Cant, Andrew J.; Hambleton, Sophie] Newcastle Univ, Inst Cellular Med, Newcastle Upon Tyne NE2 4HH, Tyne & Wear, England. [Carroll, Bernadette; Lakey, Jeremy H.; Korolchuk, Viktor I.] Newcastle Univ, Inst Cell & Mol Biosci, Newcastle Upon Tyne NE2 4HH, Tyne & Wear, England. [Robertson, Nic; Hall, Julie M.; Cant, Andrew J.; Hambleton, Sophie] Newcastle Upon Tyne Hosp NHS Fdn Trust, Great North Childrens Hosp, Newcastle Upon Tyne NE1 4LP, Tyne & Wear, England. [Griffin, Helen; Koref, Mauro F. Santibanez] Newcastle Univ, Inst Genet Med, Newcastle Upon Tyne NE1 3BZ, Tyne & Wear, England. [Sanderson, Sharon; Simon, Anna Katharina] Univ Oxford, John Radcliffe Hosp, NIHR BRC Translat Immunol Lab, Oxford OX3 9DU, England. [Morgan, Neil V.] Univ Birmingham, Coll Med & Dent Sci, Sch Clin & Expt Med, Ctr Cardiovasc Sci, Birmingham B15 2TT, W Midlands, England. [Turvey, Stuart E.] Univ British Columbia, Dept Pediat, Child & Family Res Inst, Vancouver, BC V5Z 4H4, Canada. [Turvey, Stuart E.] Univ British Columbia, BC Childrens Hosp, Vancouver, BC V5Z 4H4, Canada. [Hackett, Scott J.] Birmingham Heartlands Hosp, Paediat Immunol Dept, Birmingham B9 5SS, W Midlands, England. [Prestidge, Tim] Starship Childrens Hosp, Blood & Canc Ctr, Auckland 1142, New Zealand. [Simon, Anna Katharina] Univ Oxford, MRC Unit Human Immunol Unit, Weatherall Inst Mol Med, Oxford OX3 9DS, England. RP Hambleton, S (reprint author), Newcastle Univ, Inst Cellular Med, Newcastle Upon Tyne NE2 4HH, Tyne & Wear, England. EM sophie.hambleton@newcastle.ac.uk; hsu@niaid.nih.gov RI Su, Helen/H-9541-2015; OI Su, Helen/0000-0002-5582-9110; Turvey, Stuart/0000-0003-1599-1065; Morgan, Neil/0000-0001-6433-5692; Zhang, Qian/0000-0002-9040-3289; Griffin, Helen R/0000-0002-5288-3322 FU Intramural Research Program of the NIAID, NIH; UK MRC; Sir Jules Thorn Charitable Trust; NIHR Newcastle Biomedical Research Centre; Newcastle upon Tyne Hospitals NHS Charity; UK BBSRC; NIHR Oxford Biomedical Research Centre; Canadian Institutes of Health Research [MOP-133691] FX We thank the following people: for technical help, David Dorward, Louise Tee, Sonia Majri, Matt Biancalana, Alex Leney-Greene, Sam Drain, and Yaobo Xu; for clinical support, Angela Wang, Emily Jewel, Shanaz Pasha, and colleagues at the BC Children's Hospital and the Great North Children's Hospital; for sharing reagents, data, and equipment, Kenneth Rock, Beate Rockel, Thomas von Zglinicki, and Richard Siegel; for help with genetic investigations, Eamonn Maher and the Newcastle Exome Consortium, especially John Loughlin and Patrick Chinnery; for advice and critically reading the manuscript, Karin Engelhardt, Richard Siegel, Fengyi Wan, and Li Yu; and the patients and their families for participating in this study. This work was supported by the Intramural Research Program of the NIAID, NIH (H.C.S., M.J.L.); the UK MRC (S.H.); the Sir Jules Thorn Charitable Trust (S.H., M.F.S.K.); the NIHR Newcastle Biomedical Research Centre and the Newcastle upon Tyne Hospitals NHS Charity (S.H., M.F.S.K., V.I.K.); UK BBSRC (B.C., V.I.K.); NIHR Oxford Biomedical Research Centre (S.S., A.K.S.); and the Canadian Institutes of Health Research (S.E.T., MOP-133691). S.E.T. is a Clinical Scholar of the Michael Smith Foundation for Health Research. NR 42 TC 11 Z9 11 U1 3 U2 23 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 0092-8674 EI 1097-4172 J9 CELL JI Cell PD DEC 18 PY 2014 VL 159 IS 7 BP 1578 EP 1590 DI 10.1016/j.cell.2014.12.001 PG 13 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA AZ0FW UT WOS:000347922500012 PM 25525876 ER PT J AU Rabani, M Raychowdhury, R Jovanovic, M Rooney, M Stumpo, DJ Pauli, A Hacohen, N Schier, AF Blackshear, PJ Friedman, N Amit, I Regev, A AF Rabani, Michal Raychowdhury, Raktima Jovanovic, Marko Rooney, Michael Stumpo, Deborah J. Pauli, Andrea Hacohen, Nir Schier, Alexander F. Blackshear, Perry J. Friedman, Nir Amit, Ido Regev, Aviv TI High-Resolution Sequencing and Modeling Identifies Distinct Dynamic RNA Regulatory Strategies SO CELL LA English DT Article ID MESSENGER-RNA; HUMAN TRANSCRIPTOME; GENE-EXPRESSION; WIDESPREAD RNA; NUCLEOTIDE RESOLUTION; WIDE IDENTIFICATION; ZYGOTIC TRANSITION; PROFILING REVEALS; MAMMALIAN-CELLS; NONCODING RNAS AB Cells control dynamic transitions in transcript levels by regulating transcription, processing, and/or degradation through an integrated regulatory strategy. Here, we combine RNA metabolic labeling, rRNA-depleted RNA-seq, and DRiLL, a novel computational framework, to quantify the level; editing sites; and transcription, processing, and degradation rates of each transcript at a splice junction resolution during the LPS response of mouse dendritic cells. Four key regulatory strategies, dominated by RNA transcription changes, generate most temporal gene expression patterns. Noncanonical strategies that also employ dynamic posttranscriptional regulation control only a minority of genes, but provide unique signal processing features. We validate Tristetraprolin (TTP) as a major regulator of RNA degradation in one noncanonical strategy. Applying DRiLL to the regulation of noncoding RNAs and to zebrafish embryogenesis demonstrates its broad utility. Our study provides a new quantitative approach to discover transcriptional and posttranscriptional events that control dynamic changes in transcript levels using RNA sequencing data. C1 [Rabani, Michal; Raychowdhury, Raktima; Jovanovic, Marko; Rooney, Michael; Hacohen, Nir; Schier, Alexander F.; Regev, Aviv] Broad Inst MIT & Harvard, Cambridge, MA 02142 USA. [Rabani, Michal] MIT, Dept Elect Engn & Comp Sci, Cambridge, MA 02140 USA. [Rooney, Michael] Harvard MIT Div Hlth Sci & Technol, Cambridge, MA 02141 USA. [Stumpo, Deborah J.; Blackshear, Perry J.] NIEHS, Lab Signal Transduct, Res Triangle Pk, NC 27709 USA. [Pauli, Andrea; Schier, Alexander F.] Harvard Univ, Dept Mol & Cellular Biol, Cambridge, MA 02138 USA. [Schier, Alexander F.] Harvard Univ, FAS Ctr Syst Biol, Cambridge, MA 02138 USA. [Blackshear, Perry J.] Duke Univ, Med Ctr, Dept Med, Durham, NC 27710 USA. [Blackshear, Perry J.] Duke Univ, Med Ctr, Dept Biochem, Durham, NC 27710 USA. [Friedman, Nir] Hebrew Univ Jerusalem, Sch Comp Sci & Inst Life Sci, IL-91904 Jerusalem, Israel. [Amit, Ido] Weizmann Inst Sci, Dept Immunol, IL-76100 Rehovot, Israel. [Regev, Aviv] MIT, Howard Hughes Med Inst, Dept Biol, Cambridge, MA 02140 USA. RP Regev, A (reprint author), Broad Inst MIT & Harvard, Cambridge, MA 02142 USA. EM aregev@broadinstitute.org FU William Asbjornsen Albert Memorial fellowship; Xerox-MIT fellowship; Swiss National Science Foundation (SNSF); NIH [R01GM056211, K99-HD076935]; Human Frontier Science Program (HFSP); Centers of Excellence in Genomic Sciences (CEGS) [1P50HG006193-01]; Pioneer Award [DP1OD003958-01]; Howard Hughes Medical Institute (HHMI); Klarman Cell Observatory; United States-Israel Binational Science Foundation (BSF); European Research Council (ERC) [309788, 340712]; Israel Science Foundation (ISF) [1782/11]; I-CORE; Intramural Research Program of the NIH, National Institute of Environmental Health Sciences (NIEHS) FX We thank the Broad Genomics Platform for sequencing and C. de Boer for comments on the manuscript. Work was supported by William Asbjornsen Albert Memorial and Xerox-MIT fellowships (M.R.), the Swiss National Science Foundation (SNSF) for advanced researchers and Marie Sklodowska-Curie IOF fellowships (M.J.), NIH R01GM056211 (A.F.S.), the Human Frontier Science Program (HFSP) and NIH K99-HD076935 (A.P.), the Centers of Excellence in Genomic Sciences (CEGS) (1P50HG006193-01, N.H., I.A., A.R.), and Pioneer Award (DP1OD003958-01, A.R.), the Howard Hughes Medical Institute (HHMI), the Klarman Cell Observatory (A.R.), the United States-Israel Binational Science Foundation (BSF) (N.F.), the European Research Council (ERC) (309788, I.A.; 340712 N.F.), the Israel Science Foundation (ISF) (1782/11, I.A.), I-CORE (I.A. and N.F.), and the Intramural Research Program of the NIH, National Institute of Environmental Health Sciences (NIEHS) (P.J.B.). NR 45 TC 30 Z9 30 U1 1 U2 25 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 0092-8674 EI 1097-4172 J9 CELL JI Cell PD DEC 18 PY 2014 VL 159 IS 7 BP 1698 EP 1710 DI 10.1016/j.cell.2014.11.015 PG 13 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA AZ0FW UT WOS:000347922500021 PM 25497548 ER PT J AU Dao, A Yaro, AS Diallo, M Timbine, S Huestis, DL Kassogue, Y Traore, AI Sanogo, ZL Samake, D Lehmann, T AF Dao, A. Yaro, A. S. Diallo, M. Timbine, S. Huestis, D. L. Kassogue, Y. Traore, A. I. Sanogo, Z. L. Samake, D. Lehmann, T. TI Signatures of aestivation and migration in Sahelian malaria mosquito populations SO NATURE LA English DT Article ID ANOPHELES-GAMBIAE COMPLEX; DRY SEASON; MOLECULAR-FORMS; SUDAN SAVANNA; WEST-AFRICA; MALI; PERSISTENCE; ARABIENSIS; DIFFERENTIATION; TRANSMISSION AB During the long Sahelian dry season, mosquito vectors of malaria are expected to perish when no larval sites are available; yet, days after the first rains, mosquitoes reappear in large numbers. How these vectors persist over the 3-6-month long dry season has not been resolved, despite extensive research for over a century(1-3.) Hypotheses for vector persistence include dry-season diapause (aestivation) and long-distance migration (LDM); both are facets of vector biology that have been highly controversial owing to lack of concrete evidence. Here we show that certain species persist by a form of aestivation, while others engage in LDM. Using time-series analyses, the seasonal cycles of Anopheles coluzzii, Anopheles gambiae sensu stricto (s.s.), and Anopheles arabiensis were estimated, and their effects were found to be significant, stable and highly species-specific. Contrary to all expectations, the most complex dynamics occurred during the dry season, when the density of A. coluzzii fluctuated markedly, peaking when migration would seem highly unlikely, whereas A. gambiae s.s. was undetected. The population growth of A. coluzzii followed the first rains closely, consistent with aestivation, whereas the growth phase of both A. gambiae s.s. and A. arabiensis lagged by two months. Such a delay is incompatible with local persistence, but fits LDM. Surviving the long dry season in situ allows A. coluzzii to predominate and form the primary force of malaria transmission. Our results reveal profound ecological divergence between A. coluzzii and A. gambiae s.s., whose standing as distinct species has been challenged, and suggest that climate is one of the selective pressures that led to their speciation. Incorporating vector dormancy and LDM is key to predicting shifts in the range of malaria due to global climate change(4), and to the elimination of malaria from Africa. C1 [Dao, A.; Yaro, A. S.; Diallo, M.; Timbine, S.; Kassogue, Y.; Traore, A. I.; Sanogo, Z. L.; Samake, D.] Univ Sci Tech & Technol, ICER, Bamako, Mali. [Huestis, D. L.; Lehmann, T.] NIAID, Lab Malaria & Vector Res, NIH, Rockville, MD 20852 USA. RP Lehmann, T (reprint author), NIAID, Lab Malaria & Vector Res, NIH, Rockville, MD 20852 USA. EM tlehmann@niaid.nih.gov FU Tamaki Foundation; Division of Intramural Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health FX We thank the residents of Thierola for their hospitality and assistance with mosquito collections; J. Ribeiro, T. Wellems, P. McQueen, R. Faiman and G. Wasserberg for their comments on previous versions of this manuscript; and C. Traore, R. Sakai, R. Gwadz and T. Wellems for logistical support. This study was supported by the Tamaki Foundation and by the Division of Intramural Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health. NR 31 TC 9 Z9 9 U1 8 U2 46 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0028-0836 EI 1476-4687 J9 NATURE JI Nature PD DEC 18 PY 2014 VL 516 IS 7531 BP 387 EP + DI 10.1038/nature13987 PG 11 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA AW8BE UT WOS:000346484800045 PM 25470038 ER PT J AU Mizuguchi, T Fudenberg, G Mehta, S Belton, JM Taneja, N Folco, HD FitzGerald, P Dekker, J Mirny, L Barrowman, J Grewal, SIS AF Mizuguchi, Takeshi Fudenberg, Geoffrey Mehta, Sameet Belton, Jon-Matthew Taneja, Nitika Folco, Hernan Diego FitzGerald, Peter Dekker, Job Mirny, Leonid Barrowman, Jemima Grewal, Shiv I. S. TI Cohesin-dependent globules and heterochromatin shape 3D genome architecture in S. pombe SO NATURE LA English DT Article ID FISSION YEAST CHROMOSOMES; GENE-EXPRESSION; SACCHAROMYCES-CEREVISIAE; CHROMATIN INTERACTIONS; DROSOPHILA GENOME; HI-C; ORGANIZATION; CENTROMERES; PRINCIPLES; DOMAINS AB Eukaryotic genomes are folded into three-dimensional structures, such as self-associating topological domains, the borders of which are enriched in cohesin and CCCTC-binding factor (CTCF) required for long-range interactions(1-7). How local chromatin interactions govern higher-order folding of chromatin fibres and the function of cohesin in this process remain poorly understood. Here we perform genome-wide chromatin conformation capture (Hi-C) analysis(8) to explore the high-resolution organization of the Schizosaccharomyces pombe genome, which despite its small size exhibits fundamental features found in other eukaryotes(9). Our analyses of wild-type and mutant strains reveal key elements of chromosome architecture and genome organization. On chromosome arms, small regions of chromatin locally interact to form 'globules'. This feature requires a function of cohesin distinct from its role in sister chromatid cohesion. Cohesin is enriched at globule boundaries and its loss causes disruption of local globule structures and global chromosome territories. By contrast, heterochromatin, which loads cohesin at specific sites including pericentromeric and subtelomeric domains(9-11), is dispensable for globule formation but nevertheless affects genome organization. We show that heterochromatin mediates chromatin fibre compaction at centromeres and promotes prominent inter-arm interactions within centromere-proximal regions, providing structural constraints crucial for proper genome organization. Loss of heterochromatin relaxes constraints on chromosomes, causing an increase in intra-and inter-chromosomal interactions. Together, our analyses uncover fundamental genome folding principles that drive higher-order chromosome organization crucial for coordinating nuclear functions. C1 [Mizuguchi, Takeshi; Mehta, Sameet; Taneja, Nitika; Folco, Hernan Diego; Barrowman, Jemima; Grewal, Shiv I. S.] NCI, Lab Biochem & Mol Biol, NIH, Bethesda, MD 20892 USA. [Fudenberg, Geoffrey; Mirny, Leonid] Harvard Univ, Grad Program Biophys, Boston, MA 02115 USA. [Fudenberg, Geoffrey; Mirny, Leonid] MIT, Dept Phys, Inst Med Engn & Sci, Cambridge, MA 02139 USA. [Belton, Jon-Matthew; Dekker, Job] Univ Massachusetts, Sch Med, Program Syst Biol, Worcester, MA 01605 USA. [FitzGerald, Peter] NCI, Genome Anal Unit, NIH, Bethesda, MD 20892 USA. RP Grewal, SIS (reprint author), NCI, Lab Biochem & Mol Biol, NIH, Bethesda, MD 20892 USA. EM grewals@mail.nih.gov OI Mehta, Sameet/0000-0002-3029-3217; , /0000-0001-5905-6517 FU National Institutes of Health, National Cancer Institute; NHGRI [HG003143]; NCI Physical Sciences-Oncology Center at MIT [U54CA143874] FX We thank Y. Watanabe and M. Yanagida for strains, M. Zofall for contributions, and A. Kelly for comments. This study used the Helix Systems and the Biowulf Linux cluster at the National Institutes of Health. This work was supported by the Intramural Research Program of the National Institutes of Health, National Cancer Institute and by a grant from NHGRI (HG003143) to J.D. The work of G.F. and L.M is supported by NCI Physical Sciences-Oncology Center at MIT (U54CA143874). NR 35 TC 57 Z9 60 U1 7 U2 41 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0028-0836 EI 1476-4687 J9 NATURE JI Nature PD DEC 18 PY 2014 VL 516 IS 7531 BP 432 EP + DI 10.1038/nature13833 PG 16 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA AW8BE UT WOS:000346484800055 PM 25307058 ER PT J AU Trivellin, G Daly, AF Faucz, FR Yuan, B Rostomyan, L Larco, DO Schernthaner-Reiter, MH Szarek, E Leal, LF Caberg, JH Castermans, E Villa, C Dimopoulos, A Chittiboina, P Xekouki, P Shah, N Metzger, D Lysy, PA Ferrante, E Strebkova, N Mazerkina, N Zatelli, MC Lodish, M Horvath, A de Alexandre, RB Manning, AD Levy, I Keil, MF Sierra, MD Palmeira, L Coppieters, W Georges, M Naves, LA Jamar, M Bours, V Wu, TJ Choong, CS Bertherat, J Chanson, P Kamenicky, P Farrell, WE Barlier, A Quezado, M Bjelobaba, I Stojilkovic, SS Wess, J Costanzi, S Liu, P Lupski, JR Beckers, A Stratakis, CA AF Trivellin, G. Daly, A. F. Faucz, F. R. Yuan, B. Rostomyan, L. Larco, D. O. Schernthaner-Reiter, M. H. Szarek, E. Leal, L. F. Caberg, J. -H. Castermans, E. Villa, C. Dimopoulos, A. Chittiboina, P. Xekouki, P. Shah, N. Metzger, D. Lysy, P. A. Ferrante, E. Strebkova, N. Mazerkina, N. Zatelli, M. C. Lodish, M. Horvath, A. de Alexandre, R. Bertollo Manning, A. D. Levy, I. Keil, M. F. Sierra, M. de la Luz Palmeira, L. Coppieters, W. Georges, M. Naves, L. A. Jamar, M. Bours, V. Wu, T. J. Choong, C. S. Bertherat, J. Chanson, P. Kamenicky, P. Farrell, W. E. Barlier, A. Quezado, M. Bjelobaba, I. Stojilkovic, S. S. Wess, J. Costanzi, S. Liu, P. Lupski, J. R. Beckers, A. Stratakis, C. A. TI Gigantism and Acromegaly Due to Xq26 Microduplications and GPR101 Mutation SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Article ID PROTEIN-COUPLED RECEPTOR; ISOLATED PITUITARY-ADENOMAS; SHORT STATURE; EXPRESSION; GENE; DUPLICATION; MESSENGER; AIP AB BACKGROUND Increased secretion of growth hormone leads to gigantism in children and acromegaly in adults; the genetic causes of gigantism and acromegaly are poorly understood. METHODS We performed clinical and genetic studies of samples obtained from 43 patients with gigantism and then sequenced an implicated gene in samples from 248 patients with acromegaly. RESULTS We observed microduplication on chromosome Xq26.3 in samples from 13 patients with gigantism; of these samples, 4 were obtained from members of two unrelated kindreds, and 9 were from patients with sporadic cases. All the patients had disease onset during early childhood. Of the patients with gigantism who did not carry an Xq26.3 microduplication, none presented before the age of 5 years. Genomic characterization of the Xq26.3 region suggests that the microduplications are generated during chromosome replication and that they contain four protein-coding genes. Only one of these genes, GPR101, which encodes a G-protein-coupled receptor, was overexpressed in patients' pituitary lesions. We identified a recurrent GPR101 mutation (p.E308D) in 11 of 248 patients with acromegaly, with the mutation found mostly in tumors. When the mutation was transfected into rat GH3 cells, it led to increased release of growth hormone and proliferation of growth hormone-producing cells. CONCLUSIONS We describe a pediatric disorder (which we have termed X-linked acrogigantism [X-LAG]) that is caused by an Xq26.3 genomic duplication and is characterized by early-onset gigantism resulting from an excess of growth hormone. Duplication of GPR101 probably causes X-LAG. We also found a recurrent mutation in GPR101 in some adults with acromegaly. C1 [Trivellin, G.; Faucz, F. R.; Schernthaner-Reiter, M. H.; Szarek, E.; Leal, L. F.; Dimopoulos, A.; Xekouki, P.; Lodish, M.; Horvath, A.; de Alexandre, R. Bertollo; Manning, A. D.; Levy, I.; Keil, M. F.; Sierra, M. de la Luz; Stratakis, C. A.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Sect Endocrinol & Genet, Program Dev Endocrinol & Genet, NIH, Bethesda, MD USA. [Trivellin, G.; Faucz, F. R.; Schernthaner-Reiter, M. H.; Szarek, E.; Leal, L. F.; Dimopoulos, A.; Xekouki, P.; Lodish, M.; Horvath, A.; de Alexandre, R. Bertollo; Manning, A. D.; Levy, I.; Keil, M. F.; Sierra, M. de la Luz; Stratakis, C. A.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Pediat Endocrinol Interinst Training Program, NIH, Bethesda, MD USA. [Bjelobaba, I.; Stojilkovic, S. S.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Sect Cellular Signaling, Program Dev Neurosci, NIH, Bethesda, MD USA. [Chittiboina, P.] NINDS, Surg Neurol Branch, NIH, Bethesda, MD 20892 USA. [Quezado, M.] NCI, Pathol Lab, NIH, Bethesda, MD 20892 USA. [Wess, J.] NIDDK, Mol Signaling Sect, Bioorgan Chem Lab, NIH, Bethesda, MD USA. [Larco, D. O.; Wu, T. J.] Uniformed Serv Univ Hlth Sci, Dept Obstet & Gynecol, Bethesda, MD 20814 USA. [Daly, A. F.; Rostomyan, L.; Villa, C.; Beckers, A.] Univ Liege, Ctr Hosp Univ Liege, Dept Endocrinol, Liege, Belgium. [Caberg, J. -H.; Castermans, E.; Jamar, M.; Bours, V.] Univ Liege, Ctr Hosp Univ Liege, Dept Clin Genet, Liege, Belgium. [Palmeira, L.; Coppieters, W.; Georges, M.] Domaine Univ Sart Tilman, Grp Interdisciplinaire Genoprote Appl GIGA Genom, Liege, Belgium. [Lysy, P. A.] Catholic Univ Louvain, Clin Univ St Luc, Dept Pediat, Pediat Endocrinol Unit, Louvain, Belgium. [Faucz, F. R.; de Alexandre, R. Bertollo] Pontificia Univ Catolica Parana, Sch Hlth & Biosci, Curitiba, Parana, Brazil. [Naves, L. A.] Univ Brasilia, Fac Med, Dept Endocrinol, Brasilia, DF, Brazil. [Yuan, B.; Liu, P.; Lupski, J. R.] Baylor Coll Med, Dept Mol & Human Genet, Houston, TX 77030 USA. [Lupski, J. R.] Baylor Coll Med, Dept Pediat, Houston, TX 77030 USA. [Lupski, J. R.] Texas Childrens Hosp, Baylor Coll Med, Houston, TX 77030 USA. [Villa, C.] Hop Foch, Dept Anat & Cytol Pathol, Suresnes, France. [Villa, C.; Bertherat, J.] Univ Paris 05, Inst Cochin, Hop Cochin, INSERM,U1016,Serv Endocrinol, Paris, France. [Chanson, P.; Kamenicky, P.] Hop Univ Paris Sud, AP HP, Serv Endocrinol & Malad Reprod, Le Kremlin Bicetre, France. [Chanson, P.; Kamenicky, P.] Ctr Reference Malad Endocriniennes Rares Croissan, Le Kremlin Bicetre, France. [Chanson, P.; Kamenicky, P.] Univ Paris 11, Fac Med, UMR S693, Le Kremlin Bicetre, France. [Barlier, A.] Aix Marseille Univ, CNRS, UMR 7286, Ctr Rech Neurobiol & Neurophysiol Marseille, Marseille, France. [Shah, N.] King Edward Mem Hosp, Dept Endocrinol, Mumbai, Maharashtra, India. [Metzger, D.] BC Childrens Hosp, Endocrinol & Diabet Unit, Vancouver, BC, Canada. [Levy, I.] Hosp Sick Children, Div Endocrinol, Toronto, ON M5G 1X8, Canada. [Ferrante, E.] Fdn Ist Ricovero & Cura Carattere Sci Ca Granda O, Endocrinol & Diabetol Unit, Milan, Italy. [Zatelli, M. C.] Univ Ferrara, Dept Med Sci, Endocrinol Sect, I-44100 Ferrara, Italy. [Strebkova, N.] Inst Pediat Endocrinol, Endocrinol Res Ctr, Moscow, Russia. [Mazerkina, N.] NN Burdenko Inst Neurosurg, Moscow, Russia. [Horvath, A.] George Washington Univ, Dept Physiol & Pharmacol, Washington, DC USA. [Costanzi, S.] Amer Univ, Dept Chem, Washington, DC 20016 USA. [Costanzi, S.] Amer Univ, Ctr Behav Neurosci, Washington, DC 20016 USA. [Choong, C. S.] Princess Margaret Hosp Children, Dept Paediat Endocrinol, Perth, WA, Australia. [Choong, C. S.] Univ Western Australia, Sch Pediat & Child Hlth, Perth, WA 6009, Australia. [Farrell, W. E.] Keele Univ, Guy Hilton Res Ctr, Inst Sci & Technol Med, Stoke On Trent, Staffs, England. RP Stratakis, CA (reprint author), NIH, Clin Res Ctr, 10 Ctr Dr,Bldg 10,Rm 1-3330,MSC1103, Bethesda, MD 20892 USA. EM albert.beckers@chu.ulg.ac.be; stratakc@mail.nih.gov RI Trivellin, Giampaolo/J-6583-2016; Daly, Adrian /E-2178-2011; de Alexandre, Rodrigo/H-9489-2013; OI Trivellin, Giampaolo/0000-0003-2384-4153; Daly, Adrian /0000-0001-6130-2975; de Alexandre, Rodrigo/0000-0002-1253-7716; Rostomyan, Liliya/0000-0003-3784-2132; Zatelli, Maria Chiara/0000-0001-8408-7796; Barlier, Anne/0000-0002-3740-6173; Schernthaner-Reiter, Marie Helene/0000-0002-7972-7610 FU Eunice Kennedy Shriver National Institute of Child Health and Human Development FX Funded by the Eunice Kennedy Shriver National Institute of Child Health and Human Development and others. NR 28 TC 63 Z9 64 U1 3 U2 22 PU MASSACHUSETTS MEDICAL SOC PI WALTHAM PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA SN 0028-4793 EI 1533-4406 J9 NEW ENGL J MED JI N. Engl. J. Med. PD DEC 18 PY 2014 VL 371 IS 25 BP 2363 EP 2374 DI 10.1056/NEJMoa1408028 PG 12 WC Medicine, General & Internal SC General & Internal Medicine GA AW7DX UT WOS:000346425800005 PM 25470569 ER PT J AU Kouznetsova, J Sun, W Martinez-Romero, C Tawa, G Shinn, P Chen, CZ Schimmer, A Sanderson, P McKew, JC Zheng, W Garcia-Sastre, A AF Kouznetsova, Jennifer Sun, Wei Martinez-Romero, Carles Tawa, Gregory Shinn, Paul Chen, Catherine Z. Schimmer, Aaron Sanderson, Philip McKew, John C. Zheng, Wei Garcia-Sastre, Adolfo TI Identification of 53 compounds that block Ebola virus-like particle entry via a repurposing screen of approved drugs SO EMERGING MICROBES & INFECTIONS LA English DT Article DE Antipsychotics; drug repurposing screen; Ebola virus; Ebola virus glycoprotein; estrogen receptor modulator; microtubule inhibitor; virus entry; VP40 ID CARDIAC-GLYCOSIDES; CELL-LINES; DISEASE; GLYCOPROTEIN; TRANSFECTION; DRONEDARONE; INHIBITION; THERAPY; CANCER; ALPHA AB In light of the current outbreak of Ebola virus disease, there is an urgent need to develop effective therapeutics to treat Ebola infection, and drug repurposing screening is a potentially rapid approach for identifying such therapeutics. We developed a biosafety level 2 (BSL-2) 1536-well plate assay to screen for entry inhibitors of Ebola virus-like particles (VLPs) containing the glycoprotein (GP) and the matrix VP40 protein fused to a beta-lactamase reporter protein and applied this assay for a rapid drug repurposing screen of Food and Drug Administration (FDA)-approved drugs. We report here the identification of 53 drugs with activity of blocking Ebola VLP entry into cells. These 53 active compounds can be divided into categories including microtubule inhibitors, estrogen receptor modulators, antihistamines, antipsychotics, pump/channel antagonists, and anticancer/antibiotics. Several of these compounds, including microtubule inhibitors and estrogen receptor modulators, had previously been reported to be active in BSL-4 infectious Ebola virus replication assays and in animal model studies. Our assay represents a robust, effective and rapid high-throughput screen for the identification of lead compounds in drug development for the treatment of Ebola virus infection. C1 [Kouznetsova, Jennifer; Sun, Wei; Tawa, Gregory; Shinn, Paul; Chen, Catherine Z.; Sanderson, Philip; McKew, John C.; Zheng, Wei] NIH, Natl Ctr Adv Translat Sci, Bethesda, MD 20892 USA. [Martinez-Romero, Carles; Garcia-Sastre, Adolfo] Icahn Sch Med Mt Sinai, Dept Microbiol, New York, NY 10029 USA. [Martinez-Romero, Carles; Garcia-Sastre, Adolfo] Icahn Sch Med Mt Sinai, Global Hlth & Emerging Pathogens Inst, New York, NY 10029 USA. [Schimmer, Aaron] Univ Hlth Network, Princess Margaret Canc Ctr, Toronto, ON M5T 2M9, Canada. [Garcia-Sastre, Adolfo] Icahn Sch Med Mt Sinai, Dept Med, Div Infect Dis, New York, NY 10029 USA. RP Zheng, W (reprint author), NIH, Natl Ctr Adv Translat Sci, Bethesda, MD 20892 USA. EM wzheng@mail.nih.gov; Adolfo.Garcia-Sastre@mssm.edu RI Zheng, Wei/J-8889-2014; OI Zheng, Wei/0000-0003-1034-0757; Garcia-Sastre, Adolfo/0000-0002-6551-1827; Martinez-Romero, Carles/0000-0001-8888-7715 FU Intramural Research Program of the NCATS; NIH; NIH [R01AI079110, R01AI089539] FX The authors would like to thank the compound management group at NCATS, National Institutes of Health (NIH), for their professional support, as well as Richard Cadagan and Osman Lizardo for excellent technical support at the Icahn School of Medicine at Mount Sinai, New York, USA. This work was supported by the Intramural Research Program of the NCATS, and the NIH. Antiviral screen assays in Adolfo Garcia-Sastre's lab are supported by NIH grants R01AI079110 and R01AI089539. NR 31 TC 34 Z9 36 U1 4 U2 19 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 2222-1751 J9 EMERG MICROBES INFEC JI Emerg. Microbes Infect. PD DEC 17 PY 2014 VL 3 AR e84 DI 10.1038/emi.2014.88 PG 7 WC Immunology; Microbiology SC Immunology; Microbiology GA CF1MD UT WOS:000352308900001 PM 26038505 ER PT J AU Wang, LY Sacks, FM Furtado, JD Ricks, M Courville, AB Sumner, AE AF Wang, Liyun Sacks, Frank M. Furtado, Jeremy D. Ricks, Madia Courville, Amber B. Sumner, Anne E. TI Racial differences between African-American and white women in insulin resistance and visceral adiposity are associated with differences in apoCIII containing apoAI and apoB lipoproteins SO NUTRITION & METABOLISM LA English DT Article DE ApoAI; ApoCIII; HDL; ApoB lipoproteins; Visceral adipose tissue; Insulin resistance; African-Americans; Coronary heart disease ID APOLIPOPROTEIN-C-III; NUTRITION EXAMINATION SURVEY; LOW-DENSITY LIPOPROTEINS; CORONARY-HEART-DISEASE; TRIGLYCERIDE LEVELS; METABOLIC SYNDROME; CARDIOVASCULAR EVENTS; ETHNIC-DIFFERENCES; HEPATIC STEATOSIS; NATIONAL-HEALTH AB Background: African-Americans have higher HDL, less visceral adipose tissue (VAT) and lower triglyceride (TG) and apoCIII concentrations than whites, despite being more insulin-resistant. We studied in African-American and white women the influences of insulin resistance and VAT on the apoAI concentrations of two HDL subspecies, one that contains apoCIII that is associated with increased risk of coronary heart disease (CHD) and one that does not have apoCIII that is associated with decreased CHD; and on the apoCIII concentrations of HDL and of the apoB lipoproteins. Methods: The participants were 32 women (14 African-Americans, 18 white) of similar age (39 +/- 12 vs. 42 +/- 11y). Mean BMI was 34 kg/m(2) in the African-Americans compared to 30 in the whites. A standard diet (33% fat, 52% carbohydrate, 15% protein) was provided for 7 days followed by a test meal (40% fat, 40% carbohydrate, 20% protein) on Day 8. Insulin sensitivity index (SI) was calculated from the minimal model. Results: After controlling for SI, African-Americans have a higher mean apoAI level in HDL with apoCIII compared with whites (12.9 +/- 2.8 and 10.9 +/- 2.9 mg/dL, respectively, P = 0.05). S I was associated with higher apoAI in HDL with apoCIII, whereas VAT was not associated with this HDL subspecies. This pattern of results was reversed for apoCIII concentrations in apoB lipoproteins. After adjusting for SI, African-Americans had lower apoCIII in apoB lipoproteins. SI was associated with lower apoCIII in total apoB lipoproteins, whereas VAT was associated with higher apoCIII in all the apoB lipoproteins. Additional adjustment for VAT tended to reduce the difference in apoCIII between the groups. Conclusions: African-American women have a higher HDL with apoCIII level than whites when controlled for insulin sensitivity. African-Americans have lower insulin sensitivity. Insulin sensitivity is associated with higher levels of HDL with apoCIII. ApoCIII levels in VLDL are lower in African-American women than whites, also affected by insulin sensitivity which is associated with low apoCIII in VLDL. VAT has a strong association with apoCIII in apoB lipoproteins but not with apoAI in HDL with apoCIII. C1 [Wang, Liyun; Sacks, Frank M.; Furtado, Jeremy D.] Harvard Univ, Sch Publ Hlth, Dept Nutr, Boston, MA 02115 USA. [Sacks, Frank M.] Brigham & Womens Hosp, Dept Med, Channing Div Network Med, Boston, MA 02115 USA. [Sacks, Frank M.] Harvard Univ, Sch Med, Boston, MA USA. [Ricks, Madia; Sumner, Anne E.] NIDDK, Diabet Endocrinol & Obes Branch, NIH, Bethesda, MD 20892 USA. [Courville, Amber B.] NIH, Dept Nutr, Ctr Clin, Bethesda, MD 20892 USA. RP Sacks, FM (reprint author), Harvard Univ, Sch Publ Hlth, Dept Nutr, 665 Huntington Ave,Bldg 1,Room 201, Boston, MA 02115 USA. EM fsacks@hsph.harvard.edu FU intramural program of NIDDK, NIH; Nutrition Department of the Clinical Center, NIH FX Anne E. Sumner and Madia Ricks were supported by the intramural program of NIDDK, NIH. Amber B. Courville was supported by the Nutrition Department of the Clinical Center, NIH. NR 35 TC 1 Z9 1 U1 0 U2 0 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1743-7075 J9 NUTR METAB JI Nutr. Metab. PD DEC 17 PY 2014 VL 11 AR 56 DI 10.1186/1743-7075-11-56 PG 11 WC Nutrition & Dietetics SC Nutrition & Dietetics GA AX3YJ UT WOS:000346871300001 PM 25553059 ER PT J AU Rudebeck, PH Murray, EA AF Rudebeck, Peter H. Murray, Elisabeth A. TI The Orbitofrontal Oracle: Cortical Mechanisms for the Prediction and Evaluation of Specific Behavioral Outcomes SO NEURON LA English DT Review ID ORBITAL PREFRONTAL CORTEX; FRONTAL-CORTEX; NEURONAL-ACTIVITY; REWARD-VALUE; DECISION-MAKING; BASOLATERAL AMYGDALA; MACAQUE MONKEYS; RHESUS-MONKEYS; ECONOMIC VALUE; PREMOTOR CORTEX AB The orbitofrontal cortex (OFC) has long been associated with the flexible control of behavior and concepts such as behavioral inhibition, self-control, and emotional regulation. These ideas emphasize the suppression of behaviors and emotions, but OFC's affirmative functions have remained enigmatic. Here we review recent work that has advanced our understanding of this prefrontal area and how its functions are shaped through interaction with subcortical structures such as the amygdala. Recent findings have overturned theories emphasizing behavioral inhibition as OFC's fundamental function. Instead, new findings indicate that OFC provides predictions about specific outcomes associated with stimuli, choices, and actions, especially their moment-to-moment value based on current internal states. OFC function thereby encompasses a broad representation or model of an individual's sensory milieu and potential actions, along with their relationship to likely behavioral outcomes. C1 [Rudebeck, Peter H.] Icahn Sch Med Mt Sinai, Friedman Brain Inst, New York, NY 10014 USA. [Murray, Elisabeth A.] NIMH, Sect Neurobiol Learning & Memory, Neuropsychol Lab, Bethesda, MD 20892 USA. RP Rudebeck, PH (reprint author), Icahn Sch Med Mt Sinai, Friedman Brain Inst, One Gustave L Levy Pl, New York, NY 10014 USA. EM peter.rudebeck@mssm.edu; murraye@mail.nih.gov OI Rudebeck, Peter/0000-0002-1411-7555; Murray, Elisabeth/0000-0003-1450-1642 FU Intramural Research Program of the National Institute of Mental Health; Icahn School of Medicine at Mount Sinai FX This work was supported, in part, by the Intramural Research Program of the National Institute of Mental Health and an internal grant from the Icahn School of Medicine at Mount Sinai. We are indebted to Steven P. Wise for comments on an earlier version of the manuscript and Andrew Rudebeck for his contagious excitement for obscure artifacts of antiquity. NR 118 TC 44 Z9 45 U1 5 U2 40 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 0896-6273 EI 1097-4199 J9 NEURON JI Neuron PD DEC 17 PY 2014 VL 84 IS 6 BP 1143 EP 1156 DI 10.1016/j.neuron.2014.10.049 PG 14 WC Neurosciences SC Neurosciences & Neurology GA AW9JY UT WOS:000346574500008 PM 25521376 ER PT J AU Kohli, A Kottilil, S AF Kohli, Anita Kottilil, Shyam TI Assessment of Outcomes of Hepatitis C Treatment Reply SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Letter C1 [Kohli, Anita] NIH, Dept Crit Care Med, Bethesda, MD 20892 USA. [Kottilil, Shyam] Univ Maryland, Sch Med, Inst Human Virol, Baltimore, MD 21201 USA. RP Kottilil, S (reprint author), Univ Maryland, Med Ctr, Inst Human Virol, 725 W Lombard St, Baltimore, MD 21201 USA. EM skottilil@niaid.nih.gov NR 2 TC 0 Z9 0 U1 0 U2 0 PU AMER MEDICAL ASSOC PI CHICAGO PA 330 N WABASH AVE, STE 39300, CHICAGO, IL 60611-5885 USA SN 0098-7484 EI 1538-3598 J9 JAMA-J AM MED ASSOC JI JAMA-J. Am. Med. Assoc. PD DEC 17 PY 2014 VL 312 IS 23 BP 2571 EP 2571 DI 10.1001/jama.2014.14905 PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA AW5YN UT WOS:000346346900024 PM 25514309 ER PT J AU Yang, MQ Elnitski, L AF Yang, Mary Qu Elnitski, Laura TI Orthology-driven mapping of bidirectional promoters in human and mouse genomes SO BMC BIOINFORMATICS LA English DT Article ID CANCER; ATLAS AB Background: The presence of bidirectional promoters in all vertebrate species suggests that the promoters may be maintained in orthologous positions. Therefore the identification of the comprehensive orthologous mapping of this type promoter across species can facilitate elucidation of regulatory mechanisms controlling bidirectional gene expression. However, the lack of annotation for many transcribed regions in the genome can impact the orthology designation of these promoters. Human and mouse are among genomes that have been relatively well annotated. Thus we used them as models to study the orthologous patterns of bidirectional promoters. Results: We developed a method to annotate these regulatory regions by confirming the orthology of the genes found on each side of the promoters. In this manuscript we report the cross-species comparisons between human and mouse genomes, where the bidirectional promoter sets regulating UCSC Known Genes and spliced EST annotations were mapped from human to mouse and vice versa. We validate hundreds of orthologous bidirectional promoters through the presence of orthologous flanking gene annotations in the second species. We also show that regulatory activity of these orthologous promoters confers similar gene expression profiles in 21 tissues of human and mouse. In particular, more than one third of human bidirectional promoters annotated from spliced EST annotations regulate ncRNA, of which over 90% are lncRNAs. Conclusions: Although evolutionary conservation shows a weaker signature in promoters than coding regions, our technique of mapping of orthologous genes shows that most bidirectional promoter arrangements are conserved across human and mouse genomes, suggesting a critical function. In addition, the similar expression patterns of the orthologous gene sets indicate that the regulatory mechanisms remain largely conserved as well. C1 [Yang, Mary Qu] Univ Arkansas, George W Donaghey Coll Engn & Informat Technol, Dept Informat Sci, MidSouth Bioinformat Ctr, Little Rock, AR 72204 USA. [Yang, Mary Qu] Univ Arkansas, Joint Bioinformat Grad Program, Little Rock, AR 72204 USA. [Yang, Mary Qu] Univ Arkansas Med Sci, Little Rock, AR 72204 USA. [Elnitski, Laura] NHGRI, NIH, Rockville, MD 20852 USA. RP Yang, MQ (reprint author), Univ Arkansas, George W Donaghey Coll Engn & Informat Technol, Dept Informat Sci, MidSouth Bioinformat Ctr, 2801 S Univ Ave, Little Rock, AR 72204 USA. EM mqyang@ualr.edu; elnitski@mail.nih.gov FU NIH [5P20GM10342913]; ASTA [15-B-23]; National Human Genome Research Institute, National Institutes of Health (NIH) FX This work and publication were funded by the intramural research program of the National Human Genome Research Institute, National Institutes of Health (NIH). In addition, MQY was also supported by NIH 5P20GM10342913 and ASTA award #15-B-23. NR 15 TC 2 Z9 2 U1 1 U2 3 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1471-2105 J9 BMC BIOINFORMATICS JI BMC Bioinformatics PD DEC 16 PY 2014 VL 15 SU 17 AR S1 DI 10.1186/1471-2105-15-S17-S1 PG 9 WC Biochemical Research Methods; Biotechnology & Applied Microbiology; Mathematical & Computational Biology SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Mathematical & Computational Biology GA CH4AS UT WOS:000353973500002 PM 25559261 ER PT J AU Hall, FS Sora, I Hen, R Uhl, GR AF Hall, Frank Scott Sora, Ichiro Hen, Rene Uhl, George R. TI Serotonin/Dopamine Interactions in a Hyperactive Mouse: Reduced Serotonin Receptor 1B Activity Reverses Effects of Dopamine Transporter Knockout SO PLOS ONE LA English DT Article ID ATTENTION-DEFICIT/HYPERACTIVITY DISORDER; PREPULSE INHIBITION DEFICITS; NUCLEUS ACCUMBENS SEPTI; VENTRAL TEGMENTAL AREA; 5-HT1B RECEPTOR; LOCOMOTOR-ACTIVITY; MICE LACKING; IN-VIVO; 5-HYDROXYTRYPTAMINE(1B) RECEPTORS; AGGRESSIVE-BEHAVIOR AB Knockout (KO) mice that lack the dopamine transporter (SL6A3; DAT) display increased locomotion that can be attenuated, under some circumstances, by administration of drugs that normally produce psychostimulant-like effects, such as amphetamine and methylphenidate. These results have led to suggestions that DAT KO mice may model features of attention deficit hyperactivity disorder (ADHD) and that these drugs may act upon serotonin (5-HT) systems to produce these unusual locomotor decreasing effects. Evidence from patterns of brain expression and initial pharmacologic studies led us to use genetic and pharmacologic approaches to examine the influence of altered 5-HT1B receptor activity on hyperactivity in DAT KO mice. Heterozygous 5-HT1B KO and pharmacologic 5-HT1B antagonism both attenuated locomotor hyperactivity in DAT KO mice. Furthermore, DAT KO mice with reduced, but not eliminated, 5-HT1B receptor expression regained cocaine-stimulated locomotion, which was absent in DAT KO mice with normal levels of 5-HT1B receptor expression. Further experiments demonstrated that the degree of habituation to the testing apparatus determined whether cocaine had no effect on locomotion in DAT KO or reduced locomotion, helping to resolve differences among prior reports. These findings of complementation of the locomotor effects of DAT KO by reducing 5-HT1B receptor activity underscore roles for interactions between specific 5-HT receptors and dopamine (DA) systems in basal and cocaine-stimulated locomotion and support evaluation of 5-HT1B antagonists as potential, non-stimulant ADHD therapeutics. C1 [Hall, Frank Scott] Univ Toledo, Coll Pharm & Pharmaceut Sci, Dept Pharmacol, Toledo, OH 43606 USA. [Hall, Frank Scott; Uhl, George R.] NIDA, Mol Neurobiol Branch, Intramural Res Program, Baltimore, MD USA. [Sora, Ichiro] Kobe Univ, Grad Sch Med, Kobe, Hyogo 657, Japan. [Hen, Rene] Columbia Univ, Dept Pharmacol, New York, NY USA. [Hen, Rene] Columbia Univ, Dept Neurosci, New York, NY USA. [Hen, Rene] Columbia Univ, Dept Pharmacol, New York, NY USA. [Hen, Rene] New York State Psychiat Inst & Hosp, Div Integrat Neurosci, New York, NY 10032 USA. RP Hall, FS (reprint author), Univ Toledo, Coll Pharm & Pharmaceut Sci, Dept Pharmacol, 2801 W Bancroft St, Toledo, OH 43606 USA. EM frank.hall@utoledo.edu RI Hall, Frank/C-3036-2013 OI Hall, Frank/0000-0002-0822-4063 FU National Institute on Drug Abuse, Intramural Research Program (NIH/DHHS, USA) FX This research was supported by the National Institute on Drug Abuse, Intramural Research Program (NIH/DHHS, USA). The funder had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 83 TC 3 Z9 3 U1 1 U2 3 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA SN 1932-6203 J9 PLOS ONE JI PLoS One PD DEC 16 PY 2014 VL 9 IS 12 AR e115009 DI 10.1371/journal.pone.0115009 PG 20 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA CA8DI UT WOS:000349146300025 PM 25514162 ER PT J AU Cosgrove, KP Mckay, R Esterlis, I Kloczynski, T Perkins, E Bois, F Pittman, B Lancaster, J Glahn, DC O'Malley, S Carson, RE Krystal, JH AF Cosgrove, Kelly P. McKay, Reese Esterlis, Irina Kloczynski, Tracy Perkins, Evgenia Bois, Frederic Pittman, Brian Lancaster, Jack Glahn, David C. O'Malley, Stephanie Carson, Richard E. Krystal, John H. TI Tobacco smoking interferes with GABA(A) receptor neuroadaptations during prolonged alcohol withdrawal SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE alcohol dependence; tobacco smoking; neuroimaging; GABA(A) receptors; translational ID BENZODIAZEPINE-RECEPTORS; CIGARETTE-SMOKING; CESSATION TREATMENT; DELTA-SUBUNIT; A RECEPTORS; BINDING; DEPENDENCE; PET; SPECT; ETHANOL AB Understanding the effects of tobacco smoking on neuroadaptations in GABA(A) receptor levels over alcohol withdrawal will provide critical insights for the treatment of comorbid alcohol and nicotine dependence. We conducted parallel studies in human subjects and nonhuman primates to investigate the differential effects of tobacco smoking and nicotine on changes in GABA(A) receptor availability during acute and prolonged alcohol withdrawal. We report that alcohol withdrawal with or without concurrent tobacco smoking/nicotine consumption resulted in significant and robust elevations in GABA(A) receptor levels over the first week of withdrawal. Over prolonged withdrawal, GABA(A) receptors returned to control levels in alcohol-dependent nonsmokers, but alcohol-dependent smokers had significant and sustained elevations in GABA(A) receptors that were associated with craving for alcohol and cigarettes. In nonhuman primates, GABA(A) receptor levels normalized by 1 mo of abstinence in both groups-that is, those that consumed alcohol alone or the combination of alcohol and nicotine. These data suggest that constituents in tobacco smoke other than nicotine block the recovery of GABA(A) receptor systems during sustained alcohol abstinence, contributing to alcohol relapse and the perpetuation of smoking. C1 [Cosgrove, Kelly P.; McKay, Reese; Esterlis, Irina; Kloczynski, Tracy; Perkins, Evgenia; Bois, Frederic; Pittman, Brian; Glahn, David C.; O'Malley, Stephanie; Krystal, John H.] Yale Univ, Sch Med, Yale PET Ctr, Dept Psychiat, New Haven, CT 06510 USA. [Cosgrove, Kelly P.; Krystal, John H.] Yale Univ, Sch Med, Yale PET Ctr, Dept Neurobiol, New Haven, CT 06510 USA. [Cosgrove, Kelly P.; Esterlis, Irina; Carson, Richard E.] Yale Univ, Sch Med, Yale PET Ctr, Dept Diagnost Radiol, New Haven, CT 06510 USA. [Cosgrove, Kelly P.; Esterlis, Irina; Krystal, John H.] VA Connecticut Healthcare Syst, VA Natl Ctr PTSD, Clin Neurosci Div, West Haven, CT 06516 USA. [Cosgrove, Kelly P.; Esterlis, Irina; Pittman, Brian; O'Malley, Stephanie; Krystal, John H.] NIAAA, Ctr Translat Neurosci Alcoholism, New Haven, CT 06510 USA. [McKay, Reese; Glahn, David C.] Olin Neuropsychiatr Res Ctr, Inst Living, Hartford, CT 06114 USA. [Lancaster, Jack] Univ Texas Hlth Sci Ctr San Antonio, Res Imaging Inst, San Antonio, TX 78229 USA. RP Krystal, JH (reprint author), Yale Univ, Sch Med, Yale PET Ctr, Dept Psychiat, New Haven, CT 06510 USA. EM kelly.cosgrove@yale.edu RI Carson, Richard/H-3250-2011 OI Carson, Richard/0000-0002-9338-7966 FU Center for Translational Neuroscience of Alcoholism; US Department of Veterans Affairs Alcohol Center; US Department of Veterans Affairs Clinical Neuroscience Division; National Center for PTSD; National Institute on Alcohol Abuse and Alcoholism [R01AA17464, R01AA11321, P50-AA-12870]; National Institute on Drug Abuse [K02DA031750]; Yale Center for Clinical Investigation [UL1 RR024139]; State of Connecticut Support for the Clinical Neuroscience Research Unit FX We thank the Institute for Neurodegenerative Disorders, the Yale PET Center, the late Dr. Julie Staley, and Lou Amici for imaging and chemistry support. We thank Dr. Peter Jatlow for analysis of plasma nicotine and cotinine. We thank the staff of the CNRU of the Abraham Ribicoff Research Facilities of the Connecticut Mental Health Center. This work was supported by the Center for Translational Neuroscience of Alcoholism, US Department of Veterans Affairs Alcohol Center, US Department of Veterans Affairs Clinical Neuroscience Division, National Center for PTSD, National Institute on Alcohol Abuse and Alcoholism (R01AA17464, R01AA11321, and P50-AA-12870), National Institute on Drug Abuse (K02DA031750), the Yale Center for Clinical Investigation (UL1 RR024139), and the State of Connecticut Support for the Clinical Neuroscience Research Unit. NR 42 TC 6 Z9 7 U1 1 U2 6 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD DEC 16 PY 2014 VL 111 IS 50 BP 18031 EP 18036 DI 10.1073/pnas.1413947111 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA AW6GA UT WOS:000346366500078 PM 25453062 ER PT J AU Jourdan, T Szanda, G Rosenberg, AZ Tam, J Earley, BJ Godlewski, G Cinar, R Liu, ZY Liu, J Ju, C Pacher, P Kunos, G AF Jourdan, Tony Szanda, Gergo Rosenberg, Avi Z. Tam, Joseph Earley, Brian James Godlewski, Grzegorz Cinar, Resat Liu, Ziyi Liu, Jie Ju, Cynthia Pacher, Pal Kunos, George TI Overactive cannabinoid 1 receptor in podocytes drives type 2 diabetic nephropathy SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE endocannabinoid; podocyte; angiotensin II; nephropathy; hyperglycemia ID ANGIOTENSIN-II; FATTY RATS; KIDNEY-DISEASE; TRANSCRIPTIONAL REGULATION; ENDOCANNABINOID SYSTEM; INSULIN-RESISTANCE; EPITHELIAL-CELLS; RENAL-FAILURE; CB1 RECEPTORS; URIC-ACID AB Diabetic nephropathy is a major cause of end-stage kidney disease, and overactivity of the endocannabinoid/cannabinoid 1 receptor (CB1R) system contributes to diabetes and its complications. Zucker diabetic fatty (ZDF) rats develop type 2 diabetic nephropathy with albuminuria, reduced glomerular filtration, activation of the reninangiotensin system (RAS), oxidative/nitrative stress, podocyte loss, and increased CB1R expression in glomeruli. Peripheral CB1R blockade initiated in the prediabetic stage prevented these changes or reversed them when animals with fully developed diabetic nephropathy were treated. Treatment of diabetic ZDF rats with losartan, an angiotensin II receptor-1 (Agtr1) antagonist, attenuated the development of nephropathy and down-regulated renal cortical CB1R expression, without affecting the marked hyperglycemia. In cultured human podocytes, CB1R and desmin gene expression were increased and podocin and nephrin content were decreased by either the CB1R agonist arachydonoyl-2'-chloroethylamide, angiotensin II, or high glucose, and the effects of all three were antagonized by CB1R blockade or siRNA-mediated knockdown of CNR1 (the cannabinoid type 1 receptor gene). We conclude that increased CB1R signaling in podocytes contributes to the development of diabetic nephropathy and represents a common pathway through which both hyperglycemia and increased RAS activity exert their deleterious effects, highlighting the therapeutic potential of peripheral CB1R blockade. C1 [Jourdan, Tony; Szanda, Gergo; Tam, Joseph; Earley, Brian James; Godlewski, Grzegorz; Cinar, Resat; Liu, Ziyi; Liu, Jie; Kunos, George] NIDDK, Lab Physiol Studies, Sect Neuroendocrinol, NIAAA,NIH, Bethesda, MD 20892 USA. [Pacher, Pal] NIDDK, Lab Physiol Studies, Sect Oxidat Stress & Tissue Injury, NIAAA,NIH, Bethesda, MD 20892 USA. [Rosenberg, Avi Z.] NIDDK, Kidney Dis Sect, NIH, Bethesda, MD 20892 USA. [Rosenberg, Avi Z.] Johns Hopkins Univ, Sch Med, Baltimore, MD 21205 USA. [Ju, Cynthia] Univ Colorado, Skaggs Sch Pharm & Pharmaceut Sci, Dept Pharmaceut Sci, Aurora, CO 80045 USA. RP Jourdan, T (reprint author), NIDDK, Lab Physiol Studies, Sect Neuroendocrinol, NIAAA,NIH, Bethesda, MD 20892 USA. EM jourdant@mail.nih.gov; george.kunos@nih.gov RI Pacher, Pal/B-6378-2008; OI Pacher, Pal/0000-0001-7036-8108; Rosenberg, Avi/0000-0003-2356-950X; CINAR, RESAT/0000-0002-8597-7253; Earley, Brian/0000-0002-6707-6785 FU National Institute on Alcohol Abuse and Alcoholism, National Institutes of Health. FX We thank Drs. J. F. McElroy and R. J. Chorvat (Jenrin Discovery) for providing the cannabinoid 1 receptor antagonist JD5037, Dr. J. Kopp (National Institute on Diabetes, Digestive, and Kidney Diseases, National Institutes of Health) for providing the human podocyte cell line and for helpful comments on the manuscript, Ms. J. Harvey-White for technical assistance, Dr. R. Kechrid for assistance with the animal studies, and Mr. Kris Ylaya for his help on histological preparation. This study was supported by intramural funds from the National Institute on Alcohol Abuse and Alcoholism, National Institutes of Health. NR 54 TC 6 Z9 7 U1 1 U2 6 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD DEC 16 PY 2014 VL 111 IS 50 BP E5420 EP E5428 DI 10.1073/pnas.1419901111 PG 9 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA AW6GA UT WOS:000346366500014 PM 25422468 ER PT J AU Marinelli, F Almagor, L Hiller, R Giladi, M Khananshvili, D Faraldo-Gomez, JD AF Marinelli, Fabrizio Almagor, Lior Hiller, Reuben Giladi, Moshe Khananshvili, Daniel Faraldo-Gomez, Jose D. TI Sodium recognition by the Na+/Ca2+ exchanger in the outward-facing conformation SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE secondary transporters; membrane antiporters; ion specificity; CaCA superfamily; molecular-dynamics simulations ID CALCIUM EXCHANGER; MOLECULAR-DYNAMICS; NA+-CA2+ EXCHANGER; BINDING-SITES; TRANSPORT; STOICHIOMETRY; NCX; ION; PROTEINS; RESIDUES AB Na+/Ca2+ exchangers (NCXs) are ubiquitous membrane transporters with a key role in Ca2+ homeostasis and signaling. NCXs mediate the bidirectional translocation of either Na+ or Ca2+, and thus can catalyze uphill Ca2+ transport driven by a Na+ gradient, or vice versa. In a major breakthrough, a prokaryotic NCX homolog (NCX_Mj) was recently isolated and its crystal structure determined at atomic resolution. The structure revealed an intriguing architecture consisting of two inverted-topology repeats, each comprising five transmembrane helices. These repeats adopt asymmetric conformations, yielding an outward-facing occluded state. The crystal structure also revealed four putative ion-binding sites, but the occupancy and specificity thereof could not be conclusively established. Here, we use molecular-dynamics simulations and free-energy calculations to identify the ion configuration that best corresponds to the crystallographic data and that is also thermodynamically optimal. In this most probable configuration, three Na+ ions occupy the so-called S-ext, S-Ca, and S-int sites, whereas the Smid site is occupied by one water molecule and one H+, which protonates an adjacent aspartate side chain (D240). Experimental measurements of Na+/Ca2+ and Ca2+/Ca2+ exchange by wild-type and mutagenized NCX_Mj confirm that transport of both Na+ and Ca2+ requires protonation of D240, and that this side chain does not coordinate either ion at Smid. These results imply that the ion exchange stoichiometry of NCX_Mj is 3:1 and that translocation of Na+ across the membrane is electrogenic, whereas transport of Ca2+ is not. Altogether, these findings provide the basis for further experimental and computational studies of the conformational mechanism of this exchanger. C1 [Marinelli, Fabrizio; Faraldo-Gomez, Jose D.] NHLBI, Theoret Mol Biophys Sect, NIH, Bethesda, MD 20892 USA. [Almagor, Lior; Hiller, Reuben; Giladi, Moshe; Khananshvili, Daniel] Tel Aviv Univ, Sackler Sch Med, Dept Physiol & Pharmacol, IL-69978 Tel Aviv, Israel. RP Faraldo-Gomez, JD (reprint author), NHLBI, Theoret Mol Biophys Sect, NIH, Bldg 10, Bethesda, MD 20892 USA. EM dhanan@post.tau.ac.il; jose.faraldo@nih.gov RI Faraldo-Gomez, Jose/H-7127-2016; OI Giladi, Moshe/0000-0002-8589-6920 FU Division of Intramural Research of the National Heart, Lung, and Blood Institute (National Institutes of Health); Israel Science Foundation [825/14]; Fields Estate Foundation FX We thank Prof. Youxing Jiang for helpful discussions of our simulation results. This work was funded in part by the Division of Intramural Research of the National Heart, Lung, and Blood Institute (National Institutes of Health, J.D.F.-G) and by the Israel Science Foundation Grant 825/14 (to D.K.). Financial support from the Fields Estate Foundation (to D.K.) is highly appreciated. NR 38 TC 9 Z9 9 U1 0 U2 13 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD DEC 16 PY 2014 VL 111 IS 50 BP E5354 EP E5362 DI 10.1073/pnas.1415751111 PG 9 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA AW6GA UT WOS:000346366500007 PM 25468964 ER PT J AU Mihailescu, M Krepkiy, D Milescu, M Gawrisch, K Swartz, KJ White, S AF Mihailescu, Mihaela Krepkiy, Dmitriy Milescu, Mirela Gawrisch, Klaus Swartz, Kenton J. White, Stephen TI Structural interactions of a voltage sensor toxin with lipid membranes SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE voltage sensor toxin; voltage-activated ion channel; toxin-membrane interaction; membrane structure; neutron diffraction ID DEPENDENT K+ CHANNEL; OMEGA-GRAMMOTOXIN-SIA; GATING MODIFIER TOXINS; TARANTULA TOXIN; NEUTRON-DIFFRACTION; MAGNETIC-RESONANCE; POTASSIUM CHANNELS; SENSING DOMAINS; ION CHANNELS; HYDROCARBON CHAINS AB Protein toxins from tarantula venom alter the activity of diverse ion channel proteins, including voltage, stretch, and ligand-activated cation channels. Although tarantula toxins have been shown to partition into membranes, and the membrane is thought to play an important role in their activity, the structural interactions between these toxins and lipid membranes are poorly understood. Here, we use solid-state NMR and neutron diffraction to investigate the interactions between a voltage sensor toxin (VSTx1) and lipid membranes, with the goal of localizing the toxin in the membrane and determining its influence on membrane structure. Our results demonstrate that VSTx1 localizes to the headgroup region of lipid membranes and produces a thinning of the bilayer. The toxin orients such that many basic residues are in the aqueous phase, all three Trp residues adopt interfacial positions, and several hydrophobic residues are within the membrane interior. One remarkable feature of this preferred orientation is that the surface of the toxin that mediates binding to voltage sensors is ideally positioned within the lipid bilayer to favor complex formation between the toxin and the voltage sensor. C1 [Mihailescu, Mihaela] Univ Maryland, Inst Biosci & Biotechnol Res, Rockville, MD 20850 USA. [Mihailescu, Mihaela] NIST, Ctr Neutron Res, Gaithersburg, MD 20899 USA. [Krepkiy, Dmitriy; Milescu, Mirela; Swartz, Kenton J.] NINDS, Porter Neurosci Res Ctr, Mol Physiol & Biophys Sect, NIH, Bethesda, MD 20892 USA. [Milescu, Mirela] Univ Missouri, Div Biol, Columbia, MO 65211 USA. [Gawrisch, Klaus] NIAAA, Lab Membrane Biochem & Biophys, NIH, Bethesda, MD 20892 USA. [White, Stephen] Univ Calif Irvine, Dept Physiol & Biophys, Irvine, CA 92697 USA. RP Swartz, KJ (reprint author), NINDS, Porter Neurosci Res Ctr, Mol Physiol & Biophys Sect, NIH, Bethesda, MD 20892 USA. EM swartzk@ninds.nih.gov; Stephen.white@uci.edu FU Intramural Research Programs of the NINDS-NIH; National Institute on Alcohol Abuse and Alcoholism-NIH; NIH [GM74637]; NINDS [GM86685]; National Institute of General Medical Sciences FX We thank Howard Jaffe, Tomohiro Kimura, David Worcester, Joseph Mindell, and members of the K.J.S. and S.W. laboratories for helpful discussions. We thank Tomohiro Kimura for oriented sample NMR probe-head design. We also thank the NINDS protein sequencing facility for mass spectrometry and peptide sequencing. This work was supported by the Intramural Research Programs of the NINDS-NIH (K.J.S.) and National Institute on Alcohol Abuse and Alcoholism-NIH (K.G.), NIH Grant GM74637 (to S.W.), and Program Project GM86685 from NINDS and National Institute of General Medical Sciences (to S.W.). We are grateful for the National Institute of Standards and Technology, US Department of Commerce, in providing the neutron research facilities used for neutron diffraction experiments. NR 74 TC 15 Z9 15 U1 2 U2 23 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD DEC 16 PY 2014 VL 111 IS 50 BP E5463 EP E5470 DI 10.1073/pnas.1415324111 PG 8 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA AW6GA UT WOS:000346366500019 PM 25453087 ER PT J AU Salton, M Voss, TC Misteli, T AF Salton, Maayan Voss, Ty C. Misteli, Tom TI Identification by high-throughput imaging of the histone methyltransferase EHMT2 as an epigenetic regulator of VEGFA alternative splicing SO NUCLEIC ACIDS RESEARCH LA English DT Article ID ENDOTHELIAL GROWTH-FACTOR; LYSINE 9; HUMAN TRANSCRIPTOME; GENE-EXPRESSION; HP1 PROTEINS; CANCER CELLS; IN-VIVO; METHYLATION; H3; G9A AB Recent evidence points to a role of chromatin in regulation of alternative pre-mRNA splicing (AS). In order to identify novel chromatin regulators of AS, we screened an RNAi library of chromatin proteins using a cell-based high-throughput in vivo assay. We identified a set of chromatin proteins that regulate AS. Using simultaneous genome-wide expression and AS analysis, we demonstrate distinct and non-overlapping functions of these chromatin modifiers on transcription and AS. Detailed mechanistic characterization of one dual function chromatin modifier, the H3K9 methyltransferase EHMT2 (G9a), identified VEGFA as a major chromatin-mediated AS target. Silencing of EHMT2, or its heterodimer partner EHMT1, affects AS by promoting exclusion of VEGFA exon 6a, but does not alter total VEGFA mRNA levels. The epigenetic regulatory mechanism of AS by EHMT2 involves an adaptor system consisting of the chromatin modulator HP1 gamma, which binds methylated H3K9 and recruits splicing regulator SRSF1. The epigenetic regulation of VEGFA is physiologically relevant since EHMT2 is transcriptionally induced in response to hypoxia and triggers concomitant changes in AS of VEGFA. These results characterize a novel epigenetic regulatory mechanism of AS and they demonstrate separate roles of epigenetic modifiers in transcription and alternative splicing. C1 [Salton, Maayan; Voss, Ty C.; Misteli, Tom] NCI, NIH, Bethesda, MD 20892 USA. RP Salton, M (reprint author), NCI, NIH, Bethesda, MD 20892 USA. EM maayan.salton@gmail.com; mistelit@mail.nih.gov FU National Institutes of Health (NIH), NCI, Center for Cancer Research; NIH FX Intramural Research Program of the National Institutes of Health (NIH), NCI, Center for Cancer Research. Funding for open access charge: NIH Intramural Program. NR 63 TC 10 Z9 10 U1 1 U2 7 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0305-1048 EI 1362-4962 J9 NUCLEIC ACIDS RES JI Nucleic Acids Res. PD DEC 16 PY 2014 VL 42 IS 22 BP 13662 EP 13673 DI 10.1093/nar/gku1226 PG 12 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA AZ0DQ UT WOS:000347916900025 PM 25414343 ER PT J AU Cagliero, C Zhou, YN Jin, DJ AF Cagliero, Cedric Zhou, Yan Ning Jin, Ding Jun TI Spatial organization of transcription machinery and its segregation from the replisome in fast-growing bacterial cells SO NUCLEIC ACIDS RESEARCH LA English DT Article ID ESCHERICHIA-COLI CHROMOSOME; RIBOSOMAL-RNA TRANSCRIPTION; STRUCTURED ILLUMINATION MICROSCOPY; REPLICATION FORKS; BACILLUS-SUBTILIS; SEQA PROTEIN; POLYMERASE; ANTITERMINATION; NUSB; DNA AB In a fast-growing Escherichia coli cell, most RNA polymerase (RNAP) is allocated to rRNA synthesis forming transcription foci at clusters of rrn operons or bacterial nucleolus, and each of the several nascent nucleoids contains multiple pairs of replication forks. The composition of transcription foci has not been determined. In addition, how the transcription machinery is three-dimensionally organized to promote cell growth in concord with replication machinery in the nucleoid remains essentially unknown. Here, we determine the spatial and functional landscapes of transcription and replication machineries in fast-growing E. coli cells using super-resolution-structured illumination microscopy. Co-images of RNAP and DNA reveal spatial compartmentation and duplication of the transcription foci at the surface of the bacterial chromosome, encompassing multiple nascent nucleoids. Transcription foci cluster with NusA and NusB, which are the rrn anti-termination system and are associated with nascent rRNAs. However, transcription foci tend to separate from SeqA and SSB foci, which track DNA replication forks and/or the replisomes, demonstrating that transcription machinery and replisome are mostly located in different chromosomal territories to maintain harmony between the two major cellular functions in fast-growing cells. Our study suggests that bacterial chromosomes are spatially and functionally organized, analogous to eukaryotes. C1 [Cagliero, Cedric; Zhou, Yan Ning; Jin, Ding Jun] NCI, Transcript Control Sect, Gene Regulat & Chromosome Biol Lab, NIH, Frederick, MD 21702 USA. RP Jin, DJ (reprint author), NCI, Transcript Control Sect, Gene Regulat & Chromosome Biol Lab, NIH, Frederick, MD 21702 USA. EM jind@mail.nih.gov FU National Institutes of Health, National Cancer Institute, Center for Cancer Research; National Institutes of Health FX The Intramural Research Program of the National Institutes of Health, National Cancer Institute, Center for Cancer Research. Funding for open access charge: National Institutes of Health. NR 56 TC 6 Z9 6 U1 1 U2 9 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0305-1048 EI 1362-4962 J9 NUCLEIC ACIDS RES JI Nucleic Acids Res. PD DEC 16 PY 2014 VL 42 IS 22 BP 13696 EP 13705 DI 10.1093/nar/gku1103 PG 10 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA AZ0DQ UT WOS:000347916900028 PM 25416798 ER PT J AU Downward, GS Hu, W Rothman, N Reiss, B Wu, GP Wei, FS Chapman, RS Portengen, L Qing, L Vermeulen, R AF Downward, George S. Hu, Wei Rothman, Nat Reiss, Boris Wu, Guoping Wei, Fusheng Chapman, Robert S. Portengen, Lutzen Qing, Lan Vermeulen, Roel TI Polycyclic Aromatic Hydrocarbon Exposure in Household Air Pollution from Solid Fuel Combustion among the Female Population of Xuanwei and Fuyuan Counties, China SO ENVIRONMENTAL SCIENCE & TECHNOLOGY LA English DT Article ID LUNG-CANCER RISK; STOVE IMPROVEMENT; CURRENT PROGRESS; COAL; WEI; MORTALITY; EMISSIONS; REGION; URBAN; PAHS AB Exposure to polycyclic aromatic hydrocarbons (PAHs) from burning "smoky" (bituminous) coal has been implicated as a cause of the high lung cancer incidence in the counties of Xuanwei and Fuyuan, China. Little is known about variations in PAH exposure from throughout the region nor how fuel source and stove design affects exposure. Indoor and personal PAH exposure resulting from solid fuel combustion in Xuanwei and Fuyuan was investigated using repeated 24 h particle bound and gas-phase PAH measurements, which were collected from 163 female residents of Xuanwei and Fuyuan. 549 particle bound (283 indoor and 266 personal) and 193 gas phase (all personal) PAH measurements were collected. Mixed effect models indicated that PAH exposure was up to 6 times higher when burning smoky coal than smokeless coal and varied by up to a factor of 3 between different smoky coal geographic sources. PAH measurements from unventilated firepits were up to 5 times that of ventilated stoves. Exposure also varied between different room sizes and season of measurement. These findings indicate that PAH exposure is modulated by a variety of factors, including fuel type, coal source, and stove design. These findings may provide valuable insight into potential causes of lung cancer in the area. C1 [Downward, George S.; Reiss, Boris; Portengen, Lutzen; Vermeulen, Roel] Univ Utrecht, Div Environm Epidemiol, Inst Risk Assessment Sci, NL-3512 JE Utrecht, Netherlands. [Hu, Wei; Rothman, Nat; Qing, Lan] NCI, Div Canc Epidemiol, NIH, DHHS, Bethesda, MD 20892 USA. [Wu, Guoping; Wei, Fusheng] China Natl Environm Monitoring Ctr, Beijing 100062, Peoples R China. [Chapman, Robert S.] Chulalongkorn Univ, Coll Publ Hlth Sci, Bangkok 10330, Thailand. RP Downward, GS (reprint author), Univ Utrecht, Div Environm Epidemiol, Inst Risk Assessment Sci, NL-3512 JE Utrecht, Netherlands. EM g.s.downward@uu.nl RI Vermeulen, Roel/F-8037-2011 OI Vermeulen, Roel/0000-0003-4082-8163 FU National Institutes of Health [HHSN261201400122P] FX This project was supported by the National Institutes of Health (HHSN261201400122P) intramural research program. 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. We acknowledge Johan Beekhuizen and Meng Wang from the Institute for Risk Assessment Sciences, Utrecht University for their support in the production of Figure 1. NR 38 TC 11 Z9 12 U1 4 U2 35 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0013-936X EI 1520-5851 J9 ENVIRON SCI TECHNOL JI Environ. Sci. Technol. PD DEC 16 PY 2014 VL 48 IS 24 BP 14632 EP 14641 DI 10.1021/es504102z PG 10 WC Engineering, Environmental; Environmental Sciences SC Engineering; Environmental Sciences & Ecology GA AX1CO UT WOS:000346686100069 PM 25393345 ER PT J AU Rahma, OE Herrin, VE Ibrahim, RA Toubaji, A Bernstein, S Dakheel, O Steinberg, SM Abu Eid, R Mkrtichyan, M Berzofsky, JA Khleif, SN AF Rahma, Osama E. Herrin, Vincent E. Ibrahim, Rami A. Toubaji, Anton Bernstein, Sarah Dakheel, Omar Steinberg, Seth M. Abu Eid, Rasha Mkrtichyan, Mikayel Berzofsky, Jay A. Khleif, Samir N. TI Pre-immature dendritic cells (PIDC) pulsed with HPV16 E6 or E7 peptide are capable of eliciting specific immune response in patients with advanced cervical cancer SO JOURNAL OF TRANSLATIONAL MEDICINE LA English DT Article DE Dendritic cells; HPV16; E6; E7; Vaccine; Cervical cancer ID GYNECOLOGIC-ONCOLOGY-GROUP; HUMAN-PAPILLOMAVIRUS TYPE-16; INTRAEPITHELIAL NEOPLASIA; PARTICLE VACCINE; PHASE-III; RECURRENT; TRIAL; IMMUNOTHERAPY; CARCINOMA; CISPLATIN AB Background: The protein products of the early genes E6 and E7 in high-risk HPV types 16 and 18 have been implicated in the oncogenic capability of these viruses. Therefore, these peptides represent attractive vaccine therapy targets. Methods: Thirty-two patients with advanced cervical cancer (HPV16 or 18 positive) were treated with HPV16 E6 (18-26) (Arm A) or HPV16 E7 (12-20) peptide (Arm B) pulsed on PBMCs in order to illicit immune response against the relevant peptide on both arms. These PBMCs were cultured for a short time (48 hours only) and in the presence of GM-CSF, accordingly, they were identified as "Pre-Immature Dentritic Cells". Results: 51Cr release assay and ELISPOT demonstrated evidence of specific immune response against the relevant peptide in 10/16 (63%) evaluable patients in arm A and 7/12 (58%) in arm B. HPV16 E6 was found to be homologous to HPV18 E6 in both vivo and vitro. The median overall survival (OS) and progression free survival (PFS) for the full cohort was 10.0 and 3.5 months, respectively. There were no RECIST responses in any patient. The majority of toxicities were grade I and II. Conclusions: We demonstrated the feasibility and ability of Pre-Immature Dentritic Cells pulsed with HPV16 E6 (18-26) or HPV16 E7 (12-20) to induce a specific immune response against the relevant peptide despite the advanced disease of the cervical cancer patients treated on this trial. We believe that this observation deserves further investigations. C1 [Rahma, Osama E.; Herrin, Vincent E.; Ibrahim, Rami A.; Toubaji, Anton; Dakheel, Omar; Berzofsky, Jay A.; Khleif, Samir N.] NCI, Canc Vaccine Branch, CCR, Bethesda, MD 20892 USA. [Bernstein, Sarah] Walter Reed Natl Mil Med Ctr, Bethesda, MD 20814 USA. [Steinberg, Seth M.] NCI, Biostat & Data Management Sect, CCR, Rockville, MD 20850 USA. [Rahma, Osama E.] Univ Virginia, Charlottesville, VA 22908 USA. [Abu Eid, Rasha; Mkrtichyan, Mikayel; Khleif, Samir N.] Georgia Regents Univ, Ctr Canc, Augusta, GA 30912 USA. RP Khleif, SN (reprint author), NCI, Canc Vaccine Branch, CCR, 10 Ctr Dr, Bethesda, MD 20892 USA. EM skhleif@gru.edu 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. The content of this publication does not necessarily reflect the views or policies of the Department of Health and Human Services, nor does mention of trade names, commercial products, or organizations imply endorsement by the US Government. NR 24 TC 4 Z9 4 U1 1 U2 6 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1479-5876 J9 J TRANSL MED JI J. Transl. Med. PD DEC 16 PY 2014 VL 12 AR 353 DI 10.1186/s12967-014-0353-4 PG 10 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA AX9GZ UT WOS:000347212900001 PM 25510844 ER PT J AU Cantor, SB Brosh, RM AF Cantor, Sharon B. Brosh, Robert M., Jr. TI What is wrong with Fanconi anemia cells? SO CELL CYCLE LA English DT Article DE crosslink repair; DNA repair; FANCJ helicase; Fanconi Anemia; mismatch repair; MSH2 ID CROSS-LINK REPAIR; DNA MISMATCH REPAIR; REPLICATION PROTEIN-A; HOMOLOGOUS RECOMBINATION; DAMAGE RESPONSE; BRCA1 DEFICIENCY; TUMOR-CELLS; HUMAN MUTS; PATHWAY; RESISTANCE AB Figuring out what is wrong in Fanconi anemia (FA) patient cells is critical to understanding the contributions of the FA pathway to DNA repair and tumor suppression. Although FA patients exhibit a wide range of disease manifestation as well as severity (asymptomatic to congenital abnormalities, bone marrow failure, and cancer), cells from FA patients share underlying defects in their ability to process DNA lesions that interfere with DNA replication. In particular, FA cells are very sensitive to agents that induce DNA interstrand crosslinks (ICLs). The cause of this pronounced ICL sensitivity is not fully understood, but has been linked to the aberrant activation of DNA damage repair proteins, checkpoints and pathways. Thus, regulation of these responses through coordination of repair processing at stalled replication forks is an essential function of the FA pathway. Here, we briefly summarize some of the aberrant DNA damage responses contributing to defects in FA cells, and detail the newly-identified relationship between FA and the mismatch repair protein, MSH2. Understanding the contribution of MSH2 and/or other proteins to the replication problem in FA cells will be key to assessing therapeutic options to improve the health of FA patients. Moreover, loss of these factors, if linked to improved replication, could be a key event in the progression of FA cells to cancer cells. Likewise, loss of these factors could synergize to enhance tumorigenesis or confer chemoresistance in tumors defective in FA-BRCA pathway proteins and provide a basis for biomarkers for disease progression and response. C1 [Cantor, Sharon B.] Univ Massachusetts, Sch Med, Dept Canc Biol, UMASS Mem Canc Ctr, Worcester, MA 01655 USA. [Brosh, Robert M., Jr.] NIA, Lab Mol Gerontol, NIH, Biomed Res Ctr, Baltimore, MD 21224 USA. RP Cantor, SB (reprint author), Univ Massachusetts, Sch Med, Dept Canc Biol, UMASS Mem Canc Ctr, Worcester, MA 01655 USA. EM Sharon.Cantor@umassmed.edu FU NCI RO1 Grant [11150917]; Intramural Research Program of the National Institutes of Health, National Institute on Aging FX This work was supported by NCI RO1 Grant 11150917 (SC) and in part by the Intramural Research Program of the National Institutes of Health, National Institute on Aging (RMB). NR 75 TC 5 Z9 5 U1 0 U2 1 PU LANDES BIOSCIENCE PI AUSTIN PA 1806 RIO GRANDE ST, AUSTIN, TX 78702 USA SN 1538-4101 EI 1551-4005 J9 CELL CYCLE JI Cell Cycle PD DEC 15 PY 2014 VL 13 IS 24 BP 3823 EP 3827 DI 10.4161/15384101.2014.980633 PG 5 WC Cell Biology SC Cell Biology GA AZ6KU UT WOS:000348329600012 PM 25486020 ER PT J AU Luo, J Sun, LX Lin, X Liu, GX Yu, J Parisiadou, L Xie, CS Ding, JH Cai, HB AF Luo, Jing Sun, Lixin Lin, Xian Liu, Guoxiang Yu, Jia Parisiadou, Loukia Xie, Chengsong Ding, Jinhui Cai, Huaibin TI A calcineurin- and NFAT-dependent pathway is involved in alpha-synuclein-induced degeneration of midbrain dopaminergic neurons SO HUMAN MOLECULAR GENETICS LA English DT Article ID ACTIVATED T-CELLS; PARKINSONS-DISEASE; NUCLEAR FACTOR; BINDING PROTEIN; TRANSGENIC MICE; CALCIUM; DEATH; NEURODEGENERATION; OVEREXPRESSION; CYCLOSPORINE AB Parkinson's disease (PD), the most common degenerative movement disorder, is caused by a preferential loss of midbrain dopaminergic (mDA) neurons. Both alpha-synuclein (alpha-syn) missense and multiplication mutations have been linked to PD. However, the underlying intracellular signalling transduction pathways of alpha-syn-mediated mDA neurodegeneration remain elusive. Here, we show that transgenic expression of PD-related human alpha-syn A53T missense mutation promoted calcineurin (CN) activity and the subsequent nuclear translocation of nuclear factor of activated T cells (NFATs) in mDA neurons. alpha-syn enhanced the phosphatase activity of CN in both cell-free assays and cell lines transfected with either human wild-type or A53T alpha-syn. Furthermore, overexpression of alpha-syn A53T mutation significantly increased the CN-dependent nuclear import of NFATc3 in the mDA neurons of transgenic mice. More importantly, a pharmacological inhibition of CN by cyclosporine A (CsA) ameliorated the alpha-syn-induced loss of mDA neurons. These findings demonstrate an active involvement of CN- and NFAT-mediated signalling pathway in alpha-syn-mediated degeneration of mDA neurons in PD. C1 [Luo, Jing] Beijing Normal Univ, Dept Biochem & Mol Biol, Gene Engn & Biotechnol Beijing Key Lab, Beijing 100875, Peoples R China. [Luo, Jing; Sun, Lixin; Lin, Xian; Liu, Guoxiang; Yu, Jia; Parisiadou, Loukia; Xie, Chengsong; Cai, Huaibin] NIA, Transgen Sect, NIH, Bethesda, MD 20892 USA. [Ding, Jinhui] NIA, Bioinformat Core, Neurogenet Lab, NIH, Bethesda, MD 20892 USA. RP Cai, HB (reprint author), NIA, Transgen Sect, Neurogenet Lab, NIH, Bldg 35,Room 1A116,MSC 3707,35 Convent Dr, Bethesda, MD 20892 USA. EM caih@mail.nih.gov FU National Institute on Aging [AG000928, AG000929]; National Natural Science Foundation of China [81072648, 81373389] FX This work was supported in part by the intramural research programs of National Institute on Aging (AG000928, AG000929) and by the National Natural Science Foundation of China (Project 81072648 and 81373389). NR 40 TC 8 Z9 8 U1 0 U2 4 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 15 PY 2014 VL 23 IS 24 BP 6567 EP 6574 DI 10.1093/hmg/ddu377 PG 8 WC Biochemistry & Molecular Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Genetics & Heredity GA AZ0FP UT WOS:000347921900012 PM 25051958 ER PT J AU Kumari, D Usdin, K AF Kumari, Daman Usdin, Karen TI Polycomb group complexes are recruited to reactivated FMR1 alleles in Fragile X syndrome in response to FMR1 transcription SO HUMAN MOLECULAR GENETICS LA English DT Article ID DNA METHYLATION; HISTONE MODIFICATIONS; MAMMALIAN-CELLS; MESSENGER-RNA; CGG REPEAT; STEM-CELLS; GENE; CANCER; HYPERMETHYLATION; DEMETHYLATION AB The FMR1 geneis subject to repeat mediated-gene silencingwhentheCGG-repeat tract in the 5' UTR exceeds 200 repeat units. This results in Fragile X syndrome, the most common heritable cause of intellectual disability and a major cause of autism spectrum disorders. The mechanism of gene silencing is not fully understood, and efforts to reverse this gene silencing have had limited success. Here, we show that the level of trimethylation of histone H3 on lysine 27, a hallmark of the activity of EZH2, a component of repressive Polycomb Group (PcG) complexes like PRC2, is increased on reactivation of the silenced allele by either the DNA demethylating agent 5-azadeoxycytidine or the SIRT1 inhibitor splitomicin. The level of H3K27me3 increases and decreases in parallel with the FMR1 mRNA level. Furthermore, reducing the levels of the FMR1 mRNA reduces the accumulation of H3K27me3. This suggests a model for FMR1 gene silencing in which the FMR1 mRNA generated from the reactivated allele acts in cis to repress its own transcription via the recruitment of PcG complexes to the FMR1 locus. C1 [Kumari, Daman; Usdin, Karen] Natl Inst Diabet Digest & Kidney Dis, Sect Gene Struct & Dis, Lab Cell & Mol Biol, NIH, Bethesda, MD 20892 USA. RP Usdin, K (reprint author), NIH, Bldg 8,Room 2A19,8 Ctr Dr MSC 0830, Bethesda, MD 20892 USA. EM ku@helix.nih.gov FU National Institute of Diabetes, Digestive and Kidney Diseases, National Institutes of Health FX This work was supported by a grant from the Intramural program of the National Institute of Diabetes, Digestive and Kidney Diseases, National Institutes of Health to K.U. NR 43 TC 7 Z9 7 U1 0 U2 6 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 15 PY 2014 VL 23 IS 24 BP 6575 EP 6583 DI 10.1093/hmg/ddu378 PG 9 WC Biochemistry & Molecular Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Genetics & Heredity GA AZ0FP UT WOS:000347921900013 PM 25055869 ER PT J AU Wang, ZM Zhu, B Zhang, MF Parikh, H Jia, JP Chung, CC Sampson, JN Hoskins, JW Hutchinson, A Burdette, L Ibrahim, A Hautman, C Raj, PS Abnet, CC Adjei, AA Ahlbom, A Albanes, D Allen, NE Ambrosone, CB Aldrich, M Amiano, P Amos, C Andersson, U Andriole, G Andrulis, IL Arici, C Arslan, AA Austin, MA Baris, D Barkauskas, DA Bassig, BA Freeman, LEB Berg, CD Berndt, SI Bertazzi, PA Biritwum, RB Black, A Blot, W Boeing, H Boffetta, P Bolton, K Boutron-Ruault, MC Bracci, PM Brennan, P Brinton, LA Brotzman, M Bueno-de-Mesquita, HB Buring, JE Butler, MA Cai, QY Cancel-Tassin, G Canzian, F Cao, GW Caporaso, NE Carrato, A Carreon, T Carta, A Chang, GC Chang, IS Chang-Claude, J Che, X Chen, CJ Chen, CY Chen, CH Chen, C Chen, KY Chen, YM Chokkalingam, AP Chu, LW Clavel-Chapelon, F Colditz, GA Colt, JS Conti, D Cook, MB Cortessis, VK Crawford, ED Cussenot, O Davis, FG De Vivo, I Deng, X Ding, T Dinney, CP Di Stefano, AL Diver, WR Duell, EJ Elena, JW Fan, JH Feigelson, HS Feychting, M Figueroa, JD Flanagan, AM Fraumeni, JF Freedman, ND Fridley, BL Fuchs, CS Gago-Dominguez, M Gallinger, S Gao, YT Gapstur, SM Garcia-Closas, M Garcia-Closas, R Gastier-Foster, JM Gaziano, JM Gerhard, DS Giffen, CA Giles, GG Gillanders, EM Giovannucci, EL Goggins, M Gokgoz, N Goldstein, AM Gonzalez, C Gorlick, R Greene, MH Gross, M Grossman, HB Grubb, R Gu, J Guan, P Haiman, CA Hallmans, G Hankinson, SE Harris, CC Hartge, P Hattinger, C Hayes, RB He, QC Helman, L Henderson, BE Henriksson, R Hoffman-Bolton, J Hohensee, C Holly, EA Hong, YC Hoover, RN Hosgood, HD Hsiao, CF Hsing, AW Hsiung, CA Hu, N Hu, W Hu, ZB Huang, MS Hunter, DJ Inskip, PD Ito, H Jacobs, EJ Jacobs, KB Jenab, M Ji, BT Johansen, C Johansson, M Johnson, A Kaaks, R Kamat, AM Kamineni, A Karagas, M Khanna, C Khaw, KT Kim, C Kim, IS Kim, JH Kim, YH Kim, YC Kim, YT Kang, CH Jung, YJ Kitahara, CM Klein, AP Klein, R Kogevinas, M Koh, WP Kohno, T Kolonel, LN Kooperberg, C Kratz, CP Krogh, V Kunitoh, H Kurtz, RC Kurucu, N Lan, Q Lathrop, M Lau, CC Lecanda, F Lee, KM Lee, MP Le Marchand, L Lerner, SP Li, DH Liao, LM Lim, WY Lin, DX Lin, J Lindstrom, S Linet, MS Lissowska, J Liu, JJ Ljungberg, B Lloreta, J Lu, DR Ma, J Malats, N Mannisto, S Marina, N Mastrangelo, G Matsuo, K McGlynn, KA McKean-Cowdin, R McNeill, LH McWilliams, RR Melin, BS Meltzer, PS Mensah, JE Miao, XP Michaud, DS Mondul, AM Moore, LE Muir, K Niwa, S Olson, SH Orr, N Panico, S Park, JY Patel, AV Patino-Garcia, A Pavanello, S Peeters, PHM Peplonska, B Peters, U Petersen, GM Picci, P Pike, MC Porru, S Prescott, J Pu, X Purdue, MP Qiao, YL Rajaraman, P Riboli, E Risch, HA Rodabough, RJ Rothman, N Ruder, AM Ryu, JS Sanson, M Schned, A Schumacher, FR Schwartz, AG Schwartz, KL Schwenn, M Scotlandi, K Seow, A Serra, C Serra, M Sesso, HD Severi, G Shen, HB Shen, M Shete, S Shiraishi, K Shu, XO Siddiq, A Sierrasesumaga, L Sierri, S Sihoe, ADL Silverman, DT Simon, M Southey, MC Spector, L Spitz, M Stampfer, M Stattin, P Stern, MC Stevens, VL Stolzenberg-Solomon, RZ Stram, DO Strom, SS Su, WC Sund, M Sung, SW Swerdlow, A Tan, W Tanaka, H Tang, W Tang, ZZ Tardon, A Tay, E Taylor, PR Tettey, Y Thomas, DM Tirabosco, R Tjonneland, A Tobias, GS Toro, JR Travis, RC Trichopoulos, D Troisi, R Truelove, A Tsai, YH Tucker, MA Tumino, R Van Den Berg, D Van Den Eeden, SK Vermeulen, R Vineis, P Visvanathan, K Vogel, U Wang, CY Wang, CF Wang, JW Wang, SS Weiderpass, E Weinstein, SJ Wentzensen, N Wheeler, W White, E Wiencke, JK Wolk, A Wolpin, BM Wong, MP Wrensch, M Wu, C Wu, TC Wu, XF Wu, YL Wunder, JS Xiang, YB Xu, J Yang, HP Yang, PC Yatabe, Y Ye, YQ Yeboah, ED Yin, ZH Ying, C Yu, CJ Yu, K Yuan, JM Zanetti, KA Zeleniuch-Jacquotte, A Zheng, W Zhou, BS Mirabello, L Savage, SA Kraft, P Chanock, SJ Yeager, M Landi, MT Shi, JX Chatterjee, N Amundadottir, LT AF Wang, Zhaoming Zhu, Bin Zhang, Mingfeng Parikh, Hemang Jia, Jinping Chung, Charles C. Sampson, Joshua N. Hoskins, Jason W. Hutchinson, Amy Burdette, Laurie Ibrahim, Abdisamad Hautman, Christopher Raj, Preethi S. Abnet, Christian C. Adjei, Andrew A. Ahlbom, Anders Albanes, Demetrius Allen, Naomi E. Ambrosone, Christine B. Aldrich, Melinda Amiano, Pilar Amos, Christopher Andersson, Ulrika Andriole, Gerald, Jr. Andrulis, Irene L. Arici, Cecilia Arslan, Alan A. Austin, Melissa A. Baris, Dalsu Barkauskas, Donald A. Bassig, Bryan A. Freeman, Laura E. Beane Berg, Christine D. Berndt, Sonja I. Bertazzi, Pier Alberto Biritwum, Richard B. Black, Amanda Blot, William Boeing, Heiner Boffetta, Paolo Bolton, Kelly Boutron-Ruault, Marie-Christine Bracci, Paige M. Brennan, Paul Brinton, Louise A. Brotzman, Michelle Bueno-de-Mesquita, H. Bas Buring, Julie E. Butler, Mary Ann Cai, Qiuyin Cancel-Tassin, Geraldine Canzian, Federico Cao, Guangwen Caporaso, Neil E. Carrato, Alfredo Carreon, Tania Carta, Angela Chang, Gee-Chen Chang, I-Shou Chang-Claude, Jenny Che, Xu Chen, Chien-Jen Chen, Chih-Yi Chen, Chung-Hsing Chen, Constance Chen, Kuan-Yu Chen, Yuh-Min Chokkalingam, Anand P. Chu, Lisa W. Clavel-Chapelon, Francoise Colditz, Graham A. Colt, Joanne S. Conti, David Cook, Michael B. Cortessis, Victoria K. Crawford, E. David Cussenot, Olivier Davis, Faith G. De Vivo, Immaculata Deng, Xiang Ding, Ti Dinney, Colin P. Di Stefano, Anna Luisa Diver, W. Ryan Duell, Eric J. Elena, Joanne W. Fan, Jin-Hu Feigelson, Heather Spencer Feychting, Maria Figueroa, Jonine D. Flanagan, Adrienne M. Fraumeni, Joseph F., Jr. Freedman, Neal D. Fridley, Brooke L. Fuchs, Charles S. Gago-Dominguez, Manuela Gallinger, Steven Gao, Yu-Tang Gapstur, Susan M. Garcia-Closas, Montserrat Garcia-Closas, Reina Gastier-Foster, Julie M. Gaziano, J. Michael Gerhard, Daniela S. Giffen, Carol A. Giles, Graham G. Gillanders, Elizabeth M. Giovannucci, Edward L. Goggins, Michael Gokgoz, Nalan Goldstein, Alisa M. Gonzalez, Carlos Gorlick, Richard Greene, Mark H. Gross, Myron Grossman, H. Barton Grubb, Robert, III Gu, Jian Guan, Peng Haiman, Christopher A. Hallmans, Goran Hankinson, Susan E. Harris, Curtis C. Hartge, Patricia Hattinger, Claudia Hayes, Richard B. He, Qincheng Helman, Lee Henderson, Brian E. Henriksson, Roger Hoffman-Bolton, Judith Hohensee, Chancellor Holly, Elizabeth A. Hong, Yun-Chul Hoover, Robert N. Hosgood, H. Dean Hsiao, Chin-Fu Hsing, Ann W. Hsiung, Chao Agnes Hu, Nan Hu, Wei Hu, Zhibin Huang, Ming-Shyan Hunter, David J. Inskip, Peter D. Ito, Hidemi Jacobs, Eric J. Jacobs, Kevin B. Jenab, Mazda Ji, Bu-Tian Johansen, Christoffer Johansson, Mattias Johnson, Alison Kaaks, Rudolf Kamat, Ashish M. Kamineni, Aruna Karagas, Margaret Khanna, Chand Khaw, Kay-Tee Kim, Christopher Kim, In-Sam Kim, Jin Hee Kim, Yeul Hong Kim, Young-Chul Kim, Young Tae Kang, Chang Hyun Jung, Yoo Jin Kitahara, Cari M. Klein, Alison P. Klein, Robert Kogevinas, Manolis Koh, Woon-Puay Kohno, Takashi Kolonel, Laurence N. Kooperberg, Charles Kratz, Christian P. Krogh, Vittorio Kunitoh, Hideo Kurtz, Robert C. Kurucu, Nilgun Lan, Qing Lathrop, Mark Lau, Ching C. Lecanda, Fernando Lee, Kyoung-Mu Lee, Maxwell P. Le Marchand, Loic Lerner, Seth P. Li, Donghui Liao, Linda M. Lim, Wei-Yen Lin, Dongxin Lin, Jie Lindstrom, Sara Linet, Martha S. Lissowska, Jolanta Liu, Jianjun Ljungberg, Boerje Lloreta, Josep Lu, Daru Ma, Jing Malats, Nuria Mannisto, Satu Marina, Neyssa Mastrangelo, Giuseppe Matsuo, Keitaro McGlynn, Katherine A. McKean-Cowdin, Roberta McNeill, Lorna H. McWilliams, Robert R. Melin, Beatrice S. Meltzer, Paul S. Mensah, James E. Miao, Xiaoping Michaud, Dominique S. Mondul, Alison M. Moore, Lee E. Muir, Kenneth Niwa, Shelley Olson, Sara H. Orr, Nick Panico, Salvatore Park, Jae Yong Patel, Alpa V. Patino-Garcia, Ana Pavanello, Sofia Peeters, Petra H. M. Peplonska, Beata Peters, Ulrike Petersen, Gloria M. Picci, Piero Pike, Malcolm C. Porru, Stefano Prescott, Jennifer Pu, Xia Purdue, Mark P. Qiao, You-Lin Rajaraman, Preetha Riboli, Elio Risch, Harvey A. Rodabough, Rebecca J. Rothman, Nathaniel Ruder, Avima M. Ryu, Jeong-Seon Sanson, Marc Schned, Alan Schumacher, Fredrick R. Schwartz, Ann G. Schwartz, Kendra L. Schwenn, Molly Scotlandi, Katia Seow, Adeline Serra, Consol Serra, Massimo Sesso, Howard D. Severi, Gianluca Shen, Hongbing Shen, Min Shete, Sanjay Shiraishi, Kouya Shu, Xiao-Ou Siddiq, Afshan Sierrasesumaga, Luis Sierri, Sabina Sihoe, Alan Dart Loon Silverman, Debra T. Simon, Matthias Southey, Melissa C. Spector, Logan Spitz, Margaret Stampfer, Meir Stattin, Par Stern, Mariana C. Stevens, Victoria L. Stolzenberg-Solomon, Rachael Z. Stram, Daniel O. Strom, Sara S. Su, Wu-Chou Sund, Malin Sung, Sook Whan Swerdlow, Anthony Tan, Wen Tanaka, Hideo Tang, Wei Tang, Ze-Zhang Tardon, Adonina Tay, Evelyn Taylor, Philip R. Tettey, Yao Thomas, David M. Tirabosco, Roberto Tjonneland, Anne Tobias, Geoffrey S. Toro, Jorge R. Travis, Ruth C. Trichopoulos, Dimitrios Troisi, Rebecca Truelove, Ann Tsai, Ying-Huang Tucker, Margaret A. Tumino, Rosario Van Den Berg, David Van Den Eeden, Stephen K. Vermeulen, Roel Vineis, Paolo Visvanathan, Kala Vogel, Ulla Wang, Chaoyu Wang, Chengfeng Wang, Junwen Wang, Sophia S. Weiderpass, Elisabete Weinstein, Stephanie J. Wentzensen, Nicolas Wheeler, William White, Emily Wiencke, John K. Wolk, Alicja Wolpin, Brian M. Wong, Maria Pik Wrensch, Margaret Wu, Chen Wu, Tangchun Wu, Xifeng Wu, Yi-Long Wunder, Jay S. Xiang, Yong-Bing Xu, Jun Yang, Hannah P. Yang, Pan-Chyr Yatabe, Yasushi Ye, Yuanqing Yeboah, Edward D. Yin, Zhihua Ying, Chen Yu, Chong-Jen Yu, Kai Yuan, Jian-Min Zanetti, Krista A. Zeleniuch-Jacquotte, Anne Zheng, Wei Zhou, Baosen Mirabello, Lisa Savage, Sharon A. Kraft, Peter Chanock, Stephen J. Yeager, Meredith Landi, Maria Terese Shi, Jianxin Chatterjee, Nilanjan Amundadottir, Laufey T. TI Imputation and subset-based association analysis across different cancer types identifies multiple independent risk loci in the TERT-CLPTM1L region on chromosome 5p15.33 SO HUMAN MOLECULAR GENETICS LA English DT Article ID GENOME-WIDE ASSOCIATION; SINGLE-NUCLEOTIDE POLYMORPHISM; POSTMENOPAUSAL BREAST-CANCER; TERT PROMOTER MUTATIONS; 2 SUSCEPTIBILITY LOCI; TELOMERE LENGTH; LUNG-CANCER; PROSTATE-CANCER; PANCREATIC-CANCER; DNA METHYLATION AB Genome-wide association studies (GWAS) have mapped risk alleles for at least 10 distinct cancers to a small region of 63 000 bp on chromosome 5p15.33. This region harbors the TERT and CLPTM1L genes; the former encodes the catalytic subunit of telomerase reverse transcriptase and the latter may play a role in apoptosis. To investigate further the genetic architecture of common susceptibility alleles in this region, we conducted an agnostic subset-based meta-analysis (association analysis based on subsets) across six distinct cancers in 34 248 cases and 45 036 controls. Based on sequential conditional analysis, we identified as many as six independent risk loci marked by common single-nucleotide polymorphisms: five in the TERT gene (Region 1: rs7726159, P = 2.10 x 10(-39); Region 3: rs2853677, P = 3.30 x 10(-36) and P-Conditional = 2.36 x 10(-8); Region 4: rs2736098, P = 3.87 x 10(-12) and P-Conditional = 5.19 x 10(-6), Region 5: rs13172201, P = 0.041 and P-Conditional = 2.04 x 10(-6); and Region 6: rs10069690, P = 7.49 x 10 215 and P-Conditional = 5.35 x 10(-7)) and one in the neighboring CLPTM1L gene(Region 2: rs451360; P = 1.90 x 10(-18) and P-Conditional = 7.06 x 10(-16)). Between three and five cancers mapped to each independent locus with both risk-enhancing and protective effects. Allele-specific effects on DNA methylation were seen for a subset of risk loci, indicating that methylation and subsequent effects on gene expression may contribute to the biology of risk variants on 5p15.33. Our results provide strong support for extensive pleiotropy across this region of 5p15.33, to an extent not previously observed in other cancer susceptibility loci. C1 [Wang, Zhaoming; Zhu, Bin; Zhang, Mingfeng; Parikh, Hemang; Jia, Jinping; Chung, Charles C.; Sampson, Joshua N.; Hoskins, Jason W.; Hutchinson, Amy; Burdette, Laurie; Ibrahim, Abdisamad; Hautman, Christopher; Raj, Preethi S.; Abnet, Christian C.; Albanes, Demetrius; Baris, Dalsu; Bassig, Bryan A.; Freeman, Laura E. Beane; Berndt, Sonja I.; Black, Amanda; Bolton, Kelly; Brinton, Louise A.; Caporaso, Neil E.; Colt, Joanne S.; Cook, Michael B.; Deng, Xiang; Figueroa, Jonine D.; Fraumeni, Joseph F., Jr.; Freedman, Neal D.; Garcia-Closas, Montserrat; Goldstein, Alisa M.; Greene, Mark H.; Hartge, Patricia; Hayes, Richard B.; Hoover, Robert N.; Hu, Nan; Hu, Wei; Inskip, Peter D.; Ji, Bu-Tian; Kim, Christopher; Kitahara, Cari M.; Kratz, Christian P.; Lan, Qing; Liao, Linda M.; Linet, Martha S.; McGlynn, Katherine A.; Mondul, Alison M.; Moore, Lee E.; Purdue, Mark P.; Rajaraman, Preetha; Rothman, Nathaniel; Shen, Min; Silverman, Debra T.; Stolzenberg-Solomon, Rachael Z.; Tang, Wei; Taylor, Philip R.; Tobias, Geoffrey S.; Toro, Jorge R.; Troisi, Rebecca; Tucker, Margaret A.; Wang, Chaoyu; Wang, Junwen; Weinstein, Stephanie J.; Wentzensen, Nicolas; Yang, Hannah P.; Yu, Kai; Mirabello, Lisa; Savage, Sharon A.; Chanock, Stephen J.; Yeager, Meredith; Landi, Maria Terese; Shi, Jianxin; Chatterjee, Nilanjan; Amundadottir, Laufey T.] NCI, Div Canc Epidemiol & Genet, NIH, Bethesda, MD 20892 USA. [Berg, Christine D.] NCI, Div Canc Prevent, NIH, Bethesda, MD 20892 USA. [Helman, Lee; Khanna, Chand; Lee, Maxwell P.; Meltzer, Paul S.] NCI, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. [Gerhard, Daniela S.; Jacobs, Kevin B.] NCI, Off Canc Genom, Dept Hlth & Human Serv, NIH, Bethesda, MD 20892 USA. [Wang, Zhaoming; Chung, Charles C.; Hutchinson, Amy; Burdette, Laurie; Hautman, Christopher; Deng, Xiang; Jacobs, Kevin B.; Wang, Junwen; Chanock, Stephen J.; Yeager, Meredith] NCI, Canc Genom Res Lab, Div Canc Epidemiol & Genet, SAIC Frederick Inc,Frederick Natl Lab Canc Res, Frederick, MD 21701 USA. [Adjei, Andrew A.; Biritwum, Richard B.; Mensah, James E.; Tay, Evelyn; Tettey, Yao; Yeboah, Edward D.] Korle Bu Teaching Hosp, Accra, Ghana. [Adjei, Andrew A.; Biritwum, Richard B.; Mensah, James E.; Tay, Evelyn; Tettey, Yao; Yeboah, Edward D.] Univ Ghana, Sch Med, Accra, Ghana. [Ahlbom, Anders; Feychting, Maria] Karolinska Inst, Epidemiol Unit, Inst Environm Med, Stockholm, Sweden. [Weiderpass, Elisabete] Karolinska Inst, Dept Med Epidemiol & Biostat, Stockholm, Sweden. [Wolk, Alicja] Karolinska Inst, Unit Nutr Epidemiol, Inst Environm Med, Stockholm, Sweden. [Allen, Naomi E.; Travis, Ruth C.] Univ Oxford, Clin Trial Serv Unit, Oxford, England. [Allen, Naomi E.; Travis, Ruth C.] Univ Oxford, Epidemiol Studies Unit, Oxford, England. [Ambrosone, Christine B.] Roswell Pk Canc Inst, Dept Canc Prevent & Control, Buffalo, NY 14263 USA. [Aldrich, Melinda; Blot, William; Cai, Qiuyin; Shu, Xiao-Ou; Zheng, Wei] Vanderbilt Univ, Sch Med, Vanderbilt Epidemiol Ctr, Div Epidemiol,Dept Med, Nashville, TN 37212 USA. [Aldrich, Melinda; Blot, William; Cai, Qiuyin; Shu, Xiao-Ou; Zheng, Wei] Vanderbilt Univ, Sch Med, Vanderbilt Ingram Canc Ctr, Nashville, TN 37212 USA. [Amiano, Pilar] Basque Reg Hlth Dept, Publ Hlth Div Gipuzkoa, San Sebastian, Spain. [Amiano, Pilar] CIBER Epidemiol & Salud Publ, CIBERESP, Madrid, Spain. [Amos, Christopher; Karagas, Margaret; Schned, Alan] Geisel Sch Med Dartmouth, Hanover, NH USA. [Andersson, Ulrika; Henriksson, Roger; Melin, Beatrice S.] Umea Univ, Dept Radiat Sci, Umea, Sweden. [Hallmans, Goran] Umea Univ, Dept Publ Hlth & Clin Med Nutr Res, Umea, Sweden. [Johansson, Mattias] Umea Univ, Dept Publ Hlth & Clin Med, Umea, Sweden. [Ljungberg, Boerje; Stattin, Par] Umea Univ, Dept Surg & Perioperat Sci, Umea, Sweden. [Sund, Malin] Umea Univ, Dept Surg & Perioperat Sci Surg, Umea, Sweden. [Andriole, Gerald, Jr.; Wunder, Jay S.] Washington Univ, Sch Med, Div Urol Surg, St Louis, MO 63110 USA. [Andrulis, Irene L.; Carta, Angela] Univ Toronto, Mt Sinai Hosp, Samuel Lunenfeld Res Inst, Litwin Ctr Canc Genet, Toronto, ON M5G 1X5, Canada. [Arici, Cecilia; Porru, Stefano] Univ Brescia, Dept Med & Surg Specialties Radiol Sci & Publ Hlt, I-25121 Brescia, Italy. [Arslan, Alan A.] NYU, Dept Obstet & Gynecol, Sch Med, New York, NY 10016 USA. 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Michael] Vet Affairs Boston Healthcare Syst, Massachusetts Vet Epidemiol, Res & Informat Ctr, Geriatr Res Educ & Clin Ctr, Boston, MA USA. [Giffen, Carol A.; Wheeler, William] Informat Management Serv Inc, Calverton, MD USA. [Giles, Graham G.; Severi, Gianluca] Univ Melbourne, Canc Epidemiol Ctr, Canc Council Victoria, Melbourne, Vic 3010, Australia. [Giles, Graham G.; Severi, Gianluca] Univ Melbourne, Ctr Mol Environm Genet & Analyt Epidemiol, Melbourne, Vic 3010, Australia. [Gillanders, Elizabeth M.] NCI, Div Canc Control & Populat Sci, Bethesda, MD 20892 USA. [Harris, Curtis C.] NCI, Human Carcinogenesis Lab, Ctr Canc Res, Bethesda, MD 20892 USA. [Goggins, Michael; Klein, Alison P.] Johns Hopkins Univ, Sch Med, Dept Oncol, Baltimore, MD 21205 USA. [Goggins, Michael; Klein, Alison P.] Johns Hopkins Univ, Sch Med, Dept Pathol, Baltimore, MD 21205 USA. [Goggins, Michael; Klein, Alison P.] Johns Hopkins Univ, Sch Med, Dept Med, Sol Goldman Pancreat Res Ctr, Baltimore, MD 21205 USA. 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[Xu, Jun] Univ Hong Kong, Sch Publ Hlth, Li Ka Shing LKS Fac Med, Hong Kong, Hong Kong, Peoples R China. [Wang, Sophia S.] City Hope Natl Med Ctr, Dept Populat Sci, Div Canc Etiol, Duarte, CA USA. [Wang, Sophia S.] City Hope Natl Med Ctr, Beckman Res Inst, Duarte, CA 91010 USA. [Weiderpass, Elisabete] Arct Univ Norway, Dept Community Med, Fac Hlth Sci, Univ Tromso, Tromso, Norway. [Weiderpass, Elisabete] Canc Registry Norway, Dept Res, Oslo, Norway. [Weiderpass, Elisabete] Samfundet Folkhalsan, Helsinki, Finland. [Wiencke, John K.; Wrensch, Margaret] Univ Calif San Francisco, San Francisco, CA 94143 USA. [Wu, Yi-Long] Guangdong Acad Med Sci, Med Res Ctr, Guangdong Lung Canc Inst, Guangzhou, Guangdong, Peoples R China. [Wu, Yi-Long] Guangdong Acad Med Sci, Ctr Canc, Guangdong Gen Hosp, Guangzhou, Guangdong, Peoples R China. [Yatabe, Yasushi] Aichi Canc Ctr Hosp, Dept Pathol & Mol Diagnost, Pittsburgh, PA USA. [Yuan, Jian-Min] Univ Pittsburgh, Inst Canc, Pittsburgh, PA USA. [Lee, Kyoung-Mu] Korea Natl Open Univ, Dept Environm Hlth, Seoul, South Korea. RP Amundadottir, LT (reprint author), NCI, Lab Translat Genom, Div Canc Epidemiol & Genet, Adv Technol Ctr, 8717 Grovemont Circle, Bethesda, MD 20892 USA. EM amundadottirl@mail.nih.gov RI Freedman, Neal/B-9741-2015; Gallinger, Steven/E-4575-2013; Albanes, Demetrius/B-9749-2015; Beane Freeman, Laura/C-4468-2015; miao, xiaoping/C-4336-2011; Andrulis, Irene/E-7267-2013; Fridley, Brooke/D-8315-2015; Hsiung, Chao Agnes/E-3994-2010; Garcia-Closas, Montserrat /F-3871-2015; Chang, I-Shou/D-2084-2010; Hsiao, Chin-Fu/E-3993-2010; Boutron-Ruault, Marie-Christine/H-3936-2014; Brinton, Louise/G-7486-2015; Serra, Massimo/J-4878-2016; Tobias, Geoffrey/M-4135-2016; Weiderpass, Elisabete/M-4029-2016; Wang, Junwen/D-3700-2011; Hattinger, Claudia/Q-1212-2016; Kitahara, Cari/R-8267-2016; Jung, Yoojin/G-2519-2015; Kogevinas, Manolis/C-3918-2017; Vermeulen, Roel/F-8037-2011; bertazzi, pietro alberto/D-5039-2017; Vogel, Ulla/I-5048-2012; Abnet, Christian/C-4111-2015; Malats, Nuria/H-7041-2015; Chen, Chien-Jen/C-6976-2008; Patino-Garcia, Ana/I-4299-2012; Tucker, Margaret/B-4297-2015; Simon, Matthias/F-3046-2014; Cook, Michael/A-5641-2009; Purdue, Mark/C-9228-2016; Savage, Sharon/B-9747-2015; Tanaka, Hideo/A-8145-2016; Krogh, Vittorio/K-2628-2016; Panico, Salvatore/K-6506-2016; Amundadottir, Laufey/L-7656-2016 OI Freedman, Neal/0000-0003-0074-1098; Beane Freeman, Laura/0000-0003-1294-4124; miao, xiaoping/0000-0002-6818-9722; Fridley, Brooke/0000-0001-7739-7956; Garcia-Closas, Montserrat /0000-0003-1033-2650; Brinton, Louise/0000-0003-3853-8562; Qiao, You-Lin/0000-0001-6380-0871; Spector, Logan/0000-0003-2516-0222; Giles, Graham/0000-0003-4946-9099; Cancel-Tassin, Geraldine/0000-0002-9583-6382; Zeleniuch-Jacquotte, Anne/0000-0001-9350-1303; Liao, Linda/0000-0002-1923-5294; Mondul, Alison/0000-0002-8843-1416; Hoskins, Jason/0000-0001-6944-1996; Hayes, Richard/0000-0002-0918-661X; Serra, Massimo/0000-0003-0742-1177; Tobias, Geoffrey/0000-0002-2878-8253; Weiderpass, Elisabete/0000-0003-2237-0128; Wang, Junwen/0000-0002-4432-4707; Hattinger, Claudia/0000-0002-9316-5095; Vermeulen, Roel/0000-0003-4082-8163; bertazzi, pietro alberto/0000-0003-3475-2449; Duell, Eric J/0000-0001-5256-0163; Vogel, Ulla/0000-0001-6807-1524; Abnet, Christian/0000-0002-3008-7843; Malats, Nuria/0000-0003-2538-3784; Cook, Michael/0000-0002-0533-7302; Purdue, Mark/0000-0003-1177-3108; Savage, Sharon/0000-0001-6006-0740; Krogh, Vittorio/0000-0003-0122-8624; Panico, Salvatore/0000-0002-5498-8312; Amundadottir, Laufey/0000-0003-1859-8971 FU US National Institutes of Health (NIH), National Cancer Institute [HHSN261200800001E]; Intramural Research Program FX This work was supported by the Intramural Research Program and by contract number HHSN261200800001E of the US National Institutes of Health (NIH), National Cancer Institute. 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. Additional funding acknowledgements are listed in Supplementary Material. The funders had no role in study design, data collection and analysis, decision to publish or preparation of the manuscript. NR 89 TC 25 Z9 25 U1 4 U2 59 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 15 PY 2014 VL 23 IS 24 BP 6616 EP 6633 DI 10.1093/hmg/ddu363 PG 18 WC Biochemistry & Molecular Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Genetics & Heredity GA AZ0FP UT WOS:000347921900017 PM 25027329 ER PT J AU Kwan, JSH Hsu, YH Cheung, CL Dupuis, J Saint-Pierre, A Eriksson, J Handelman, SK Aragaki, A Karasik, D Pramstaller, PP Kooperberg, C Lacroix, AZ Larson, MG Lau, KS Lorentzon, M Pichler, I Sham, PC Taliun, D Vandenput, L Kiel, DP Hicks, AA Jackson, RD Ohlsson, C Benjamin, EJ Kung, AWC AF Kwan, Johnny S. H. Hsu, Yi-Hsiang Cheung, Ching-Lung Dupuis, Josee Saint-Pierre, Aude Eriksson, Joel Handelman, Samuel K. Aragaki, Aaron Karasik, David Pramstaller, Peter P. Kooperberg, Charles Lacroix, Andrea Z. Larson, Martin G. Lau, Kam-Shing Lorentzon, Mattias Pichler, Irene Sham, Pak C. Taliun, Daniel Vandenput, Liesbeth Kiel, Douglas P. Hicks, Andrew A. Jackson, Rebecca D. Ohlsson, Claes Benjamin, Emelia J. Kung, Annie W. C. TI Meta-analysis of genome-wide association studies identifies two loci associated with circulating osteoprotegerin levels SO HUMAN MOLECULAR GENETICS LA English DT Article ID BREAST-CANCER CELLS; TRAIL-INDUCED APOPTOSIS; COMPLEX TRAITS; RANK LIGAND; VASCULAR CALCIFICATION; ENDOTHELIAL-CELLS; POTENTIAL MARKER; BONE METABOLISM; EXPRESSION; DISEASE AB Osteoprotegerin (OPG) is involved in bone homeostasis and tumor cell survival. Circulating OPG levels are also important biomarkers of various clinical traits, such as cancers and atherosclerosis. OPG levels were measured in serum or in plasma. In a meta-analysis of genome-wide association studies in up to 10 336 individuals from European and Asian origin, we discovered that variants > 100 kb upstream of the TNFRSF11B gene encoding OPG and another new locus on chromosome 17q11.2 were significantly associated with OPG variation. We also identified a suggestive locus on chromosome 14q21.2 associated with the trait. Moreover, we estimated that over half of the heritability of OPG levels could be explained by all variants examined in our study. Our findings provide further insight into the genetic regulation of circulating OPG levels. C1 [Kwan, Johnny S. H.; Cheung, Ching-Lung; Lau, Kam-Shing; Kung, Annie W. C.] Univ Hong Kong, Dept Med, Pokfulam, Hong Kong, Peoples R China. [Kwan, Johnny S. H.; Sham, Pak C.] Univ Hong Kong, Dept Psychiat, Pokfulam, Hong Kong, Peoples R China. [Sham, Pak C.] Univ Hong Kong, Ctr Genom Sci, Pokfulam, Hong Kong, Peoples R China. [Hsu, Yi-Hsiang; Karasik, David; Kiel, Douglas P.] Hebrew SeniorLife, Inst Aging Res, Boston, MA USA. [Hsu, Yi-Hsiang] Harvard Univ, Sch Publ Hlth, Program Quantitat Genom, Boston, MA 02115 USA. [Hsu, Yi-Hsiang; Kiel, Douglas P.] BROAD Inst MIT & Harvard, Cambridge, MA USA. [Dupuis, Josee; Larson, Martin G.; Benjamin, Emelia J.] NHLBI, Framingham Heart Study, Framingham, MA USA. [Dupuis, Josee; Larson, Martin G.; Benjamin, Emelia J.] Boston Univ, Framingham, MA USA. [Dupuis, Josee; Larson, Martin G.] Boston Univ, Sch Publ Hlth, Dept Biostat, Boston, MA USA. [Saint-Pierre, Aude; Pramstaller, Peter P.; Pichler, Irene; Taliun, Daniel; Hicks, Andrew A.] European Acad Bozen Bolzano EURAC, Ctr Biomed, Bolzano, Italy. [Saint-Pierre, Aude; Pramstaller, Peter P.; Pichler, Irene; Taliun, Daniel; Hicks, Andrew A.] Med Univ Lubeck, Affiliated Inst, D-23538 Lubeck, Germany. [Saint-Pierre, Aude] Etab Francais Sang, INSERM, U1078, Brest, France. [Eriksson, Joel; Lorentzon, Mattias; Vandenput, Liesbeth; Ohlsson, Claes] Univ Gothenburg, Dept Internal Med, Sahlgrenska Acad, Ctr Bone & Arthrit Res, Gothenburg, Sweden. [Eriksson, Joel; Lorentzon, Mattias; Vandenput, Liesbeth; Ohlsson, Claes] Univ Gothenburg, Dept Geriatr, Sahlgrenska Acad, Gothenburg, Sweden. [Handelman, Samuel K.] Ohio State Univ, Dept Pharmacol, Columbus, OH 43210 USA. [Aragaki, Aaron; Jackson, Rebecca D.] Ohio State Univ, Dept Med, Div Endocrinol Diabet & Metab, Columbus, OH 43210 USA. [Kooperberg, Charles] Fred Hutchinson Canc Res Ctr, Seattle, WA 98104 USA. [Pramstaller, Peter P.] Gen Cent Hosp, Dept Neurol, Bolzano, Italy. [Pramstaller, Peter P.] Med Univ Lubeck, Dept Neurol, D-23538 Lubeck, Germany. [Lacroix, Andrea Z.] Univ Calif San Diego, Dept Prevent Med, San Diego, CA 92103 USA. [Benjamin, Emelia J.] Boston Univ, Sch Med, Dept Med, Boston, MA 02118 USA. [Kiel, Douglas P.] Beth Israel Deaconess Med Ctr, Dept Med, Boston, MA 02215 USA. [Kiel, Douglas P.] Harvard Univ, Sch Med, Boston, MA USA. RP Kung, AWC (reprint author), Univ Hong Kong, Queen Mary Hosp, Dept Med, Pokfulam, Hong Kong, Peoples R China. EM awckung@hkucc.hku.hk RI Hicks, Andrew/E-9518-2017; OI Cheung, Ching Lung/0000-0002-6233-9144; Hicks, Andrew/0000-0001-6320-0411; Benjamin, Emelia/0000-0003-4076-2336; Kiel, Douglas/0000-0001-8474-0310; Karasik, David/0000-0002-8826-0530; Vandenput, Liesbeth/0000-0002-1712-6131 FU Hong Kong Research Grant Council; Small Project Funding HKU [201309176244, 201109176063]; Bone Health Fund of HKU Foundation; Matching Grant; CRCG Grant; Osteoporosis Research Fund of The University of Hong Kong; Swedish Research Council; Swedish Foundation for Strategic Research; COMBINE; ALF/LUA research grant from the Sahlgrenska University Hospital; Lundberg Foundation; Torsten and Ragnar Soderberg's Foundation; Novo Nordisk Foundation; Gustav V and Queen Victoria Freemason Foundation; European Commission [HEALTH-F2-2008-201865-GEFOS]; NHLBI's Framingham Heart Study [N01-HC-25195]; Affymetrix, Inc. [N02-HL-6-4278]; Ministry of Health and Department for Promotion of Educational Policies, Universities and Research of the Autonomous Province of Bolzano, South Tyrol; South Tyrolean Sparkasse Foundation; European Union Framework Program 6 EUROSPAN Project [LSHG-CT-2006-018947]; NIH [R01 AR/AG 41398]; FHS [1RO1HL64753, R01HL076784, 1 R01AG028321, 2R01H L092577] FX This work was supported by the Hong Kong Research Grant Council; the Small Project Funding HKU 201309176244 and 201109176063; the Bone Health Fund of HKU Foundation and Matching Grant; the CRCG Grant and the Osteoporosis Research Fund of The University of Hong Kong. The GOOD study was supported by the Swedish Research Council, the Swedish Foundation for Strategic Research, COMBINE, the ALF/LUA research grant from the Sahlgrenska University Hospital, the Lundberg Foundation, the Torsten and Ragnar Soderberg's Foundation, the Novo Nordisk Foundation, the Gustav V and Queen Victoria Freemason Foundation and the European Commission Grant HEALTH-F2-2008-201865-GEFOS. The Framingham Heart Study of the NHLBI, NIH and Boston University School of Medicine were supported by the NHLBI's Framingham Heart Study (N01-HC-25195) and its contract with Affymetrix, Inc. for genotyping services (N02-HL-6-4278). The WHI work was supported in part by an allocation of computing time from the Ohio Supercomputer Center and the National Institute of General Medical Sciences (U01GM092655) as well as HHSN268201100002C, NO1-6H74316, U54RR0024384 and HHSN268200960002C. The MICROS study was supported by the Ministry of Health and Department for Promotion of Educational Policies, Universities and Research of the Autonomous Province of Bolzano, South Tyrol, the South Tyrolean Sparkasse Foundation, and the European Union Framework Program 6 EUROSPAN Project (contract no. LSHG-CT-2006-018947). In addition, D.P.K. received support from NIH (Grant R01 AR/AG 41398). E.J.B. received support from the FHS grants 1RO1HL64753, R01HL076784, 1 R01AG028321 and 2R01H L092577. NR 63 TC 3 Z9 3 U1 0 U2 6 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 15 PY 2014 VL 23 IS 24 BP 6684 EP 6693 DI 10.1093/hmg/ddu386 PG 10 WC Biochemistry & Molecular Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Genetics & Heredity GA AZ0FP UT WOS:000347921900023 PM 25080503 ER PT J AU Cutler, RG Thompson, KW Camandola, S Mack, KT Mattson, MP AF Cutler, Roy G. Thompson, Kenneth W. Camandola, Simonetta Mack, Kendra T. Mattson, Mark P. TI Sphingolipid metabolism regulates development and lifespan in Caenorhabditis elegans SO MECHANISMS OF AGEING AND DEVELOPMENT LA English DT Article DE Longevity; Oxidative stress; Ceramide; Gangliosides; Sphingomyelin ID C-ELEGANS; SERINE PALMITOYLTRANSFERASE; CERAMIDE; INHIBITOR; SYNTHASE; BIOSYNTHESIS; ACCUMULATION; INTERFERENCE; REPRODUCTION; MANIPULATION AB Sphingolipids are a highly conserved lipid component of cell membranes involved in the formation of lipid raft domains that house many of the receptors and cell-to-cell signaling factors involved in regulating cell division, maturation, and terminal differentiation. By measuring and manipulating sphingolipid metabolism using pharmacological and genetic tools in Caenorhabditis elegans, we provide evidence that the synthesis and remodeling of specific ceramides (e.g., dC18:1-C24:1), gangliosides (e.g., GM1-C24:1), and sphingomyelins (e.g., dC18:1-C18:1) influence development rate and lifespan. We found that the levels of fatty acid chain desaturation and elongation in many sphingolipid species increased during development and aging, with no such changes in developmentally-arrested dauer larvae or normal adults after food withdrawal (an anti-aging intervention). Pharmacological inhibitors and small interfering RNAs directed against serine palmitoyl transferase and glucosylceramide synthase acted to slow development rate, extend the reproductive period, and increase lifespan. In contrast, worms fed an egg yolk diet rich in sphingolipids exhibited accelerated development and reduced lifespan. Our findings demonstrate that sphingolipid accumulation and remodeling are critical events that determine development rate and lifespan in the nematode model, with both development rate and aging being accelerated by the synthesis of sphingomyelin, and its metabolism to ceramides and gangliosides. Published by Elsevier Ireland Ltd C1 [Cutler, Roy G.; Thompson, Kenneth W.; Camandola, Simonetta; Mack, Kendra T.; Mattson, Mark P.] NIA, Lab Neurosci, Intramural Res Program, Baltimore, MD 21224 USA. [Mattson, Mark P.] Johns Hopkins Univ, Sch Med, Dept Neurosci, Baltimore, MD 21205 USA. RP Mattson, MP (reprint author), NIA, Lab Neurosci, Intramural Res Program, Baltimore, MD 21224 USA. EM mattsonm@grc.nia.nih.gov FU National Institute on Aging Intramural Research Program; NIH National Center for Research Resources (NCRR) FX The National Institute on Aging Intramural Research Program supported this research. We thank the Caenorhabditis Genetics Center (T. Stiernagle, University of Minnesota, Minneapolis, MN) (which is funded by the NIH National Center for Research Resources (NCRR)) and the C elegans Gene Knockout Consortium (R. Barstead, Oklahoma Medical Research Foundation, Oklahoma City, OK) for providing the nematode and E. coli strains. We would also like to thank Wendy Iser for culturing and genotyping the RNAi strains used in this work, Mark Wilson for help with editing, and Cathy Wolkow for valuable advice and technical assistance. NR 47 TC 9 Z9 9 U1 1 U2 9 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0047-6374 J9 MECH AGEING DEV JI Mech. Ageing Dev. PD DEC 15 PY 2014 VL 143 BP 9 EP 18 DI 10.1016/j.mad.2014.11.002 PG 10 WC Cell Biology; Geriatrics & Gerontology SC Cell Biology; Geriatrics & Gerontology GA CA1QJ UT WOS:000348686500002 PM 25437839 ER PT J AU Kovalenko, EI Boyko, AA Semenkov, VF Lutsenko, GV Grechikhina, MV Kanevskiy, LM Azhikina, TL Telford, WG Sapozhnikov, AM AF Kovalenko, Elena I. Boyko, Anna A. Semenkov, Victor F. Lutsenko, Gennady V. Grechikhina, Maria V. Kanevskiy, Leonid M. Azhikina, Tatyana L. Telford, William G. Sapozhnikov, Alexander M. TI ROS production, intracellular HSP70 levels and their relationship in human neutrophils: effects of age SO ONCOTARGET LA English DT Article DE Aging; neutrophils; reactive oxygen species; heat shock proteins; HSP70; cell stress ID HEAT-SHOCK PROTEINS; INNATE IMMUNE-SYSTEM; STRESS-PROTEINS; ELDERLY HUMANS; FREE-RADICALS; AGING ROS; TOR; APOPTOSIS; CHEMILUMINESCENCE; IMMUNOSENESCENCE AB ROS production and intracellular HSP70 levels were measured in human neutrophils for three age groups: young (20-59 years), elders (60-89 years) and nonagenarians (90 years and older). Elders showed higher levels of spontaneous intracellular ROS content compared with young and nonagenarian groups, which had similar intracellular ROS levels. Zymosan-induced (non-spontaneous) extracellular ROS levels were also similar for young and nonagenarians but were lower in elders. However, spontaneous extracellular ROS production increased continuously with age. Correlation analysis revealed positive relationships between HSP70 levels and zymosan-stimulated ROS production in the elder group. This was consistent with a promoting role for HSP70 in ROS-associated neutrophils response to pathogens. No positive correlation between ROS production and intracellular HSP70 levels was found for groups of young people and nonagenarians. In contrast, significant negative correlations of some ROS and HSP70 characteriscics were found for neutrophils from young people and nonagenarians. The observed difference in ROS and HSP70 correlations in elders and nonagenarians might be associated with an increased risk of mortality in older individuals less than 90 years old. C1 [Kovalenko, Elena I.; Boyko, Anna A.; Lutsenko, Gennady V.; Grechikhina, Maria V.; Kanevskiy, Leonid M.; Azhikina, Tatyana L.; Sapozhnikov, Alexander M.] Shemyakin & Ovchinnikov Inst Bioorgan Chem RAS, Moscow, Russia. [Semenkov, Victor F.] Russian State Med Univ, Ctr Gerontol, Moscow 117437, Russia. [Telford, William G.] NCI, NIH, Bethesda, MD 20892 USA. RP Kovalenko, EI (reprint author), Shemyakin & Ovchinnikov Inst Bioorgan Chem RAS, Moscow, Russia. EM kovalenelen@gmail.com RI Kovalenko, Elena/S-2086-2016 FU Russian Foundation for Basic Research [14-04-01280]; Program "Nanotechnologies & Nanomaterials" of the Russian Academy of Sciences FX This work was partly supported by the Russian Foundation for Basic Research (grant # 14-04-01280) and by the Program "Nanotechnologies & Nanomaterials" of the Russian Academy of Sciences. Authors declare no conflict of interests. NR 56 TC 4 Z9 4 U1 1 U2 3 PU IMPACT JOURNALS LLC PI ALBANY PA 6211 TIPTON HOUSE, STE 6, ALBANY, NY 12203 USA SN 1949-2553 J9 ONCOTARGET JI Oncotarget PD DEC 15 PY 2014 VL 5 IS 23 BP 11800 EP 11812 PG 13 WC Oncology; Cell Biology SC Oncology; Cell Biology GA AZ2AT UT WOS:000348037700004 PM 25514461 ER PT J AU Tham, M Tan, KW Keeble, J Wang, XJ Hubert, S Barron, L Tan, NS Kato, M Prevost-Blondel, A Angeli, V Abastado, JP AF Tham, Muly Tan, Kar Wai Keeble, Jo Wang, Xiaojie Hubert, Sandra Barron, Luke Tan, Nguan Soon Kato, Masashi Prevost-Blondel, Armelle Angeli, Veronique Abastado, Jean-Pierre TI Melanoma-initiating cells exploit M2 macrophage TGF beta and arginase pathway for survival and proliferation SO ONCOTARGET LA English DT Article DE Arginase; Macrophages; TGF beta; Tumor-initiating cell ID TUMOR-ASSOCIATED MACROPHAGES; EPITHELIAL-MESENCHYMAL TRANSITION; CANCER-ASSOCIATED FIBROBLASTS; BREAST-CANCER; STEM-CELLS; IN-VIVO; T-CELLS; GROWTH; PROGRESSION; INHIBITION AB M2 macrophages promote tumor growth and metastasis, but their interactions with specific tumor cell populations are poorly characterized. Using a mouse model of spontaneous melanoma, we showed that CD34(-) but not CD34(+) tumor-initiating cells (TICs) depend on M2 macrophages for survival and proliferation. Tumor-associated macrophages (TAMs) and macrophage-conditioned media protected CD34(-) TICs from chemotherapy in vitro. In vivo, while inhibition of CD115 suppressed the macrophage-dependent CD34(-) TIC population, chemotherapy accelerated its development. The ability of TICs to respond to TAMs was acquired during melanoma progression and immediately preceded a surge in metastatic outgrowth. TAM-derived transforming growth factor-beta (TGF beta) and polyamines produced via the Arginase pathway were critical for stimulation of TICs and synergized to promote their growth. C1 [Tham, Muly; Tan, Kar Wai; Keeble, Jo; Wang, Xiaojie; Hubert, Sandra; Abastado, Jean-Pierre] ASTAR, Singapore Immunol Network, BMSI, Singapore, Singapore. [Barron, Luke] NIAID, Parasit Dis Lab, NIH, Bethesda, MD 20892 USA. [Tan, Nguan Soon] Nanyang Technol Univ, Sch Biol Sci, Singapore 639798, Singapore. [Kato, Masashi] Nagoya Univ, Grad Sch Med, Dept Occupat & Environm Hlth, Nagoya, Aichi 4648601, Japan. [Prevost-Blondel, Armelle] Univ Paris 05, CNRS UMR, Inst Cochin, Paris, France. [Angeli, Veronique] Natl Univ Singapore, Yong Loo Lin Sch Med, Dept Microbiol, Singapore 117595, Singapore. [Tan, Kar Wai] Singapore Gen Hosp, Dept Clin Res, Singapore, Singapore. [Abastado, Jean-Pierre] Inst Rech Int Servier, Suresnes, France. RP Tham, M (reprint author), ASTAR, Singapore Immunol Network, BMSI, Singapore, Singapore. EM muly_tham@immunol.a-star.edu.sg RI KATO, Masashi/I-7250-2014 FU NIH/NIAID FX This research was funded by government funding to SIgN, A*STAR, Singapore, and supported by the NIH/NIAID. We thank the following people from SIgN: Benjamin Toh and Florent Ginhoux for helpful discussions; Karen Khoo and Lu-En Wai for assistance with necropsies; Guillaume Hoeffel for providing purified anti-CD115 antibody; Subrah Biswas for the L929 cell line; Francesca Zolezzi (Functional Genomics platform) for microarray analysis and data generation; Michael Poidinger (Bioinformatics platform) for help with data analysis; Anis Larbi's team (Flow Cytometry platform) for cell sorting; and Irfan Khalis Bi Rosdi (Mouse Core) for maintaining the RETAAD mice. We also thank Lucy Robinson of Insight Editing London for critical review and manuscript editing. NR 58 TC 10 Z9 10 U1 0 U2 7 PU IMPACT JOURNALS LLC PI ALBANY PA 6211 TIPTON HOUSE, STE 6, ALBANY, NY 12203 USA SN 1949-2553 J9 ONCOTARGET JI Oncotarget PD DEC 15 PY 2014 VL 5 IS 23 BP 12027 EP 12042 PG 16 WC Oncology; Cell Biology SC Oncology; Cell Biology GA AZ2AT UT WOS:000348037700020 PM 25294815 ER PT J AU Trimble, A Gochuico, BR Markello, TC Fischer, R Gahl, WA Lee, JK Kim, Y Burdick, MD Strieter, RM Mehrad, B AF Trimble, Aaron Gochuico, Bernadette R. Markello, Thomas C. Fischer, Roxanne Gahl, William A. Lee, Jae K. Kim, Youngchul Burdick, Marie D. Strieter, Robert M. Mehrad, Borna TI Circulating Fibrocytes as Biomarker of Prognosis in Hermansky-Pudlak Syndrome SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Article DE interstitial lung diseases; stem cells; chemoldnes; CXCR4 receptors ID IDIOPATHIC PULMONARY-FIBROSIS; INTERSTITIAL LUNG-DISEASE; ACUTE EXACERBATION; RENAL FIBROSIS; RECRUITMENT; PNEUMONIAS; TYPE-2; MODEL; FORM; CT AB Rationale: The rate of progression of most interstitial lung diseases (ILD) is unpredictable. Fibrocytes are circulating bone marrow-derived cells that have been implicated in the pathogenesis of lung fibrosis. Hermansky-Pudlak syndrome (HPS), a genetic cause of ILD in early adulthood, allows for study of biomarkers of ILD in a homogeneous population at near-certain risk of developing fibrotic lung disease. Objectives: To test the hypothesis that, in subjects with HPS, the number or phenotype of circulating fibrocytes predicts progression and outcome of ILD. Methods: We measured circulating fibrocyte counts and chemoldne levels in a cohort of subjects with HPS and healthy control subjects and correlated the results to disease outcome. Measurements and Main Results: In a cross-sectional analysis, peripheral blood fibrocyte concentrations were markedly elevated in a subset of subjects with HPS who had ILD but not subjects without lung disease or normal control subjects. The blood concentration of fibrocytes expressing the chemokine receptor CXCR4 correlated significantly with the plasma concentration of the CXCR4 ligand, CXCL12. In a longitudinal study, we found marked episodic elevations in circulating fibrocyte counts over a median follow-up period of 614 days. Elevations in both maximal values and final values of peripheral blood CXCR4(+) fibrocyte concentration were strongly associated with death from ILD. Conclusions: CXCR4(+) fibrocyte concentration may be useful as a biomarker for outcome of ILD in subjects with HPS. C1 [Trimble, Aaron; Burdick, Marie D.; Strieter, Robert M.; Mehrad, Borna] Univ Virginia, Dept Med, Charlottesville, VA USA. [Mehrad, Borna] Univ Virginia, Carter Ctr Immunol, Charlottesville, VA USA. [Gochuico, Bernadette R.; Markello, Thomas C.; Fischer, Roxanne; Gahl, William A.] NHGRI, Med Genet Branch, Bethesda, MD 20892 USA. [Markello, Thomas C.; Gahl, William A.] NHGRI, Off Clin Director, Bethesda, MD 20892 USA. [Lee, Jae K.; Kim, Youngchul] H Lee Moffitt Canc Ctr & Res Inst, Dept Biostat & Bioinformat, Tampa, FL USA. RP Mehrad, B (reprint author), POB 800546, Charlottesville, VA 22908 USA. EM mehrad@virginia.edu RI Mehrad, Borna/D-9363-2015 OI Mehrad, Borna/0000-0001-5198-065X FU National Institutes of Health [HL098526, HL098329] FX Funded by National Institutes of Health grants HL098526 and HL098329 (both to B.M.). NR 37 TC 11 Z9 11 U1 1 U2 3 PU AMER THORACIC SOC PI NEW YORK PA 25 BROADWAY, 18 FL, NEW YORK, NY 10004 USA SN 1073-449X EI 1535-4970 J9 AM J RESP CRIT CARE JI Am. J. Respir. Crit. Care Med. PD DEC 15 PY 2014 VL 190 IS 12 BP 1395 EP 1401 DI 10.1164/rccm.201407-1287OC PG 7 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA AX4IG UT WOS:000346896000014 PM 25347450 ER PT J AU Verma, SK Leikina, E Melikov, K Chernomordik, LV AF Verma, Santosh K. Leikina, Evgenia Melikov, Kamran Chernomordik, Leonid V. TI Late stages of the synchronized macrophage fusion in osteoclast formation depend on dynamin SO BIOCHEMICAL JOURNAL LA English DT Article DE cell fusion; dynamin; fusion pore expansion; lysophosphatidylcholine; osteoclast formation; syncytium formation ID CELL-CELL FUSION; BODY GIANT-CELLS; MYOBLAST FUSION; ENDOCYTOSIS; DROSOPHILA; PROTEIN; HEMIFUSION; MECHANISMS; INHIBITORS; REGULATOR AB Macrophage fusion that leads to osteoclast formation is one of the most important examples of cell cell fusion in development, tissue homoeostasis and immune response. Protein machinery that fuses macrophages remains to be identified. In the present study, we explored the fusion stage of osteoclast formation for RAW macrophage-like murine cells and for macrophages derived from human monocytes. To uncouple fusion from the preceding differentiation processes, we accumulated fusion-committed cells in the presence of LPC (lysophosphatidylcholine) that reversibly blocks membrane merger. After 16 h, we removed LPC and observed cell fusion events that would normally develop within 16 h develop instead within 30-90 min. Thus, whereas osteoclastogenesis, generally, takes several days, our approach allowed us to focus on an hour in which we observe robust fusion between the cells. Complementing syncytium formation assay with a novel membrane merger assay let us study the synchronized fusion events downstream of a local merger between two plasma membranes, but before expansion of nascent membrane connections and complete unification of the cells. We found that the expansion of membrane connections detected as a growth of multinucleated osteoclasts depends on dynamin activity. In contrast, a merger between the plasma membranes of the two cells was not affected by inhibitors of dynamin GTPase. Thus dynamin that was recently found to control late stages of myoblast fusion also controls late stages of macrophage fusion, revealing an intriguing conserved mechanistic motif shared by diverse cell cell fusion processes. C1 [Verma, Santosh K.; Leikina, Evgenia; Melikov, Kamran; Chernomordik, Leonid V.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Sect Membrane Biol, Program Phys Biol, NIH, Bethesda, MD 20892 USA. RP Chernomordik, LV (reprint author), Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Sect Membrane Biol, Program Phys Biol, NIH, Bldg 10,Room 10D05,10 Ctr Dr, Bethesda, MD 20892 USA. EM chernoml@mail.nih.gov FU Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health FX The 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 (to L.V.C.). NR 45 TC 8 Z9 8 U1 1 U2 14 PU PORTLAND PRESS LTD PI LONDON PA CHARLES DARWIN HOUSE, 12 ROGER STREET, LONDON WC1N 2JU, ENGLAND SN 0264-6021 EI 1470-8728 J9 BIOCHEM J JI Biochem. J. PD DEC 15 PY 2014 VL 464 BP 293 EP 300 DI 10.1042/BJ20141233 PN 3 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA AX4CN UT WOS:000346881700001 PM 25336256 ER PT J AU Cho, H Chung, JY Kim, S Braunschweig, T Kang, TH Kim, J Chung, EJ Hewitt, SM Kim, JH AF Cho, Hanbyoul Chung, Joon-Yong Kim, Sunghoon Braunschweig, Till Kang, Tae Heung Kim, Jennie Chung, Eun Joo Hewitt, Stephen M. Kim, Jae-Hoon TI MICA/B and ULBP1 NKG2D ligands are independent predictors of good prognosis in cervical cancer SO BMC CANCER LA English DT Article DE Cervical cancer; Tissue microarray; Immunohistochemistry; NKG2D ligands ID NATURAL-KILLER-CELLS; POOR-PROGNOSIS; RETINOIC ACID; EXPRESSION; RECEPTOR; CYTOTOXICITY; WORLDWIDE; CARCINOMA; CHAIN AB Background: NKG2D (natural killer group 2, member D) is thought to play an important role in mediating the activation of anticancer immune response. Expression of NKG2D ligands (NKG2DLs) is pronounced in malignancies and the heterogeneity of NKG2DL expression remains unclear. Here, we investigate the expression and clinical significance of NKG2DLs in cervical cancer. Methods: Immunohistochemical analyses of MICA/B, ULBP1, ULBP2, ULBP3, RAET1E, and RAET1G were performed using tissue microarray analysis of 200 cervical cancers, 327 high-grade cervical intraepithelial neoplasias (CINs), 99 low-grade CINs, and 541 matched nonadjacent normal cervical epithelial tissues and compared the data with clinicopathologic variables, including the survival of cervical cancer patients. Results: MICA/B, ULBP1, and RAET1E expression was higher in cervical cancer than in low-grade CIN (p < 0.001, p = 0.012, p = 0.013, respectively) and normal cervix (all p < 0.001). Among these markers, expression of ULBP1 was significantly different depending on patient tumor stage (p = 0.010) and tumor size (p = 0.045). ULBP1 expression was correlated with MICA/B (p < 0.001) and ULBP2 (p = 0.002) expression in cervical cancer. While MICA/B+ or ULBP1+ patients had improved disease-free survival time (p = 0.027 and p = 0.009, respectively) relative to that of the low expression group, RAET1E+ or RAET1G+ was correlated with shorter survival time (p = 0.018 and p = 0.029, respectively). However, in terms of overall survival, the ULBP1+ group had significantly longer survival time than the low expression group (p = 0.009). Multivariate analysis indicated that MICA/B+/ULBP1+ (HR = 0.16, p = 0.015) and ULBP1+ (HR = 0.31, p = 0.024) are independent prognostic factors of disease-free survival in cervical cancer. Conclusions: High expression of either ULBP1 or MICA/B and ULBP1 combined is an indicator of good prognosis in cervical cancer, suggesting their potential utility as prognostic tests in clinical assessment. C1 [Cho, Hanbyoul; Kim, Jae-Hoon] Yonsei Univ, Gangnam Severance Hosp, Dept Obstet & Gynecol, Coll Med, Seoul 135720, South Korea. [Cho, Hanbyoul; Kim, Sunghoon; Kim, Jae-Hoon] Yonsei Univ, Coll Med, Inst Womens Life Med Sci, Seoul 135720, South Korea. [Cho, Hanbyoul; Chung, Joon-Yong; Braunschweig, Till; Kim, Jennie; Hewitt, Stephen M.] NCI, Tissue Array Res Program, Pathol Lab, NIH, Bethesda, MD 20892 USA. [Kim, Sunghoon] Yonsei Univ, Coll Med, Dept Obstet & Gynecol, Severance Hosp, Seoul 135720, South Korea. [Braunschweig, Till] Rhein Westfal TH Aachen, Inst Pathol, Aachen, Germany. [Kang, Tae Heung] Konkuk Univ, Dept Immunol, Coll Med, Chungju, South Korea. [Chung, Eun Joo] NCI, Radiat Oncol Branch, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. RP Kim, JH (reprint author), NCI, Tissue Array Res Program, Pathol Lab, NIH, 10 Ctr Dr,MSC 1500, Bethesda, MD 20892 USA. EM genejock@helix.nih.gov; jaehoonkim@yuhs.ac OI Hewitt, Stephen/0000-0001-8283-1788; Chung, Joon-Yong/0000-0001-5041-5982 FU Basic Science Research Program through the National Research Foundation of Korea (NRF)-Ministry of Education, Science and Technology [2011-0007146]; Yonsei University College of Medicine [6-2014-0072]; Intramural Research Program of the National Institutes of Health, National Cancer Institute, and Center for Cancer Research FX This work was supported in part by grants from the Basic Science Research Program through the National Research Foundation of Korea (NRF), funded by the Ministry of Education, Science and Technology (2011-0007146) and faculty research grants from Yonsei University College of Medicine for 2014 (6-2014-0072) and Intramural Research Program of the National Institutes of Health, National Cancer Institute, and Center for Cancer Research. NR 34 TC 9 Z9 11 U1 0 U2 9 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1471-2407 J9 BMC CANCER JI BMC Cancer PD DEC 15 PY 2014 VL 14 AR 957 DI 10.1186/1471-2407-14-957 PG 11 WC Oncology SC Oncology GA AX9CQ UT WOS:000347202000001 PM 25510288 ER PT J AU Khan, RJ Gebreab, SY Riestra, P Xu, RH Davis, SK AF Khan, Rumana J. Gebreab, Samson Y. Riestra, Pia Xu, Ruihua Davis, Sharon K. TI Parent-offspring association of metabolic syndrome in the Framingham Heart Study SO DIABETOLOGY & METABOLIC SYNDROME LA English DT Article DE Metabolic syndrome; Parent-offspring; Abdominal obesity; Impaired fasting glucose; Framingham Heart Study ID BODY-MASS INDEX; FAMILIAL AGGREGATION; CARDIOVASCULAR-DISEASE; RISK-FACTORS; OBESITY; CHILDHOOD; COHORT; TRANSMISSION; COMPONENTS; POPULATION AB Background: Metabolic syndrome (MetS) is a clustering of five metabolic risk factors including abdominal obesity, elevated blood pressure, hypertriglyceridemia, low high-density lipoprotein cholesterol (HDL-C), and impaired fasting glucose. Few studies have fully reported the strength of clustering of these risk factors in a parent-offspring relationship. This analysis describes the associations between parents and their adult offspring in regard to MetS. It also estimates the association between each risk factor in parents and the presence of MetS in their offspring. Methods: We analyzed data for 1193 offspring (565 sons, and 628 daughters) from the Framingham Offspring Study who attended examinations 5, 6, and 7. Information about their parents was collected from examinations 13, 14 and 15 of the Framingham Original Cohort study. We used pedigree file to combine parental and offspring's data. Participants were classified as having the MetS according to the Adult Treatment Panel III criteria. Analyses were conducted separately for mothers and fathers. Logistic regression was used to estimate the associations. Results: After adjusting for age, education, smoking, alcohol consumption and physical activity level of offspring, no significant association was found between father's and their offspring's MetS. Mother's MetS was significantly and positively associated with their daughter's MetS (adjusted odds ratio or adj OR: 1.63; 95% confidence Interval, CI: 1.02-2.61), but not with their sons' MetS. When analyzed by individual components, maternal impaired glucose (adj OR: 2.03; 95% CI:1.02-9.31), abdominal obesity (adj OR: 1.56; 95% CI: 0.98-2.55) and low HDL-C (adj OR: 2.12; 95% CI: 1.36-3.32) were associated daughter's MetS. Maternal low HDL-C and raised total cholesterol showed marginal association with son's MetS. For fathers, only impaired glucose (adj OR: 4.91; 95% CI: 2.07-11.68) was associated with their daughter's MetS. Conclusions: Using the data from Framingham Heart Study, we demonstrate differential association of MetS and its components between parents and offspring. Mother's MetS was strongly related with daughter's MetS, but the association was inconsistent with son's MetS. No association was found between father's MetS and offspring's Mets. These results provide evidence that daughters with mother's MetS are in higher risk than daughters or sons with father's MetS. C1 [Khan, Rumana J.; Gebreab, Samson Y.; Riestra, Pia; Xu, Ruihua; Davis, Sharon K.] NHGRI, Cardiovasc Sect, Genom Metab Cardiovasc & Inflammatory Dis Branch, Social Epidemiol Res Unit, Bethesda, MD 20892 USA. RP Khan, RJ (reprint author), NHGRI, Cardiovasc Sect, Genom Metab Cardiovasc & Inflammatory Dis Branch, Social Epidemiol Res Unit, 10 Ctr Dr,Room 7 N316 MSC 1644, Bethesda, MD 20892 USA. EM rumana.khan@nih.gov FU National Institutes of Health, National Library of Medicine FX This research was supported by the Intramural Research Program of the National Institutes of Health, National Library of Medicine. This Manuscript was prepared using The Framingham Heart Study (FHS) datasets obtained from Biologic Specimen and Data Repository Information Coordinating Center of the National Heart, Lung, and Blood Institute (NHLBI). The authors acknowledge the enormous contributions of the FHS and NHLBI staff in creating and maintaining this data set. NR 49 TC 3 Z9 4 U1 0 U2 2 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1758-5996 J9 DIABETOL METAB SYNDR JI Diabetol. Metab. Syndr. PD DEC 15 PY 2014 VL 6 AR 140 DI 10.1186/1758-5996-6-140 PG 9 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA AX7WS UT WOS:000347123200001 PM 25584075 ER PT J AU Xia, P Liu, X Wu, B Zhang, SY Song, XY Yao, PY Lippincott-Schwartz, J Yao, XB AF Xia, Peng Liu, Xing Wu, Bing Zhang, Shuyuan Song, Xiaoyu Yao, Phil Y. Lippincott-Schwartz, Jennifer Yao, Xuebiao TI Superresolution imaging reveals structural features of EB1 in microtubule plus-end tracking SO MOLECULAR BIOLOGY OF THE CELL LA English DT Article ID BINDING-PROTEINS; CELL-MIGRATION; MITOSIS; PHOSPHORYLATION; INTERACTS; DYNAMICS; INSIGHTS; TIP150; DOMAIN; TIPS AB Visualization of specific molecules and their interactions in real time and space is essential to delineate how cellular dynamics and the signaling circuit are orchestrated. Spatial regulation of conformational dynamics and structural plasticity of protein interactions is required to rewire signaling circuitry in response to extracellular cues. We introduce a method for optically imaging intracellular protein interactions at nanometer spatial resolution in live cells, using photoactivatable complementary fluorescent (PACF) proteins. Subsets of complementary fluorescent protein molecules were activated, localized, and then bleached; this was followed by the assembly of superresolution images from aggregate position of sum interactive molecules. Using PACF, we obtained precise localization of dynamic microtubule plus-end hub protein EB1 dimers and their distinct distributions at the leading edges and in the cell bodies of migrating cells. We further delineated the structure-function relationship of EB1 by generating EB1-PACF dimers (EB1(wt):EB1(wt), EB1(wt):EB1(mt), and EB1(mt):EB1(mt)) and imaging their precise localizations in culture cells. Surprisingly, our analyses revealed critical role of a previously uncharacterized EB1 linker region in tracking microtubule plus ends in live cells. Thus PACF provides a unique approach to delineating spatial dynamics of homo-or heterodimerized proteins at the nanometer scale and establishes a platform to report the precise regulation of protein interactions in space and time in live cells. C1 [Xia, Peng; Liu, Xing; Wu, Bing; Zhang, Shuyuan; Song, Xiaoyu; Yao, Xuebiao] Univ Sci & Technol China, Anhui Key Lab Cellular Dynam & Chem Biol, Hefei 230026, Anhui, Peoples R China. [Xia, Peng; Liu, Xing; Wu, Bing; Zhang, Shuyuan; Song, Xiaoyu; Yao, Xuebiao] Univ Sci & Technol China, Ctr Integrated Imaging, Hefei Natl Lab Phys Sci Nanoscale, Hefei 230026, Anhui, Peoples R China. [Liu, Xing; Yao, Phil Y.] Univ Georgia, Morehouse Sch Med, Mol Imaging Ctr, Atlanta, GA 30310 USA. [Lippincott-Schwartz, Jennifer] Natl Inst Hlth, Bethesda, MD 20892 USA. RP Yao, XB (reprint author), Univ Sci & Technol China, Anhui Key Lab Cellular Dynam & Chem Biol, Hefei 230026, Anhui, Peoples R China. EM yaoxb@ustc.edu.cn FU Chinese 973 projects [2014CB964803, 2012CB945002, 2010CB912103]; Chinese Natural Science Foundation [31320103904, 314300054, 31271518, 91313303]; Chinese Academy of Science [KSCX1-YW-R-65]; MOST [2009DFA31010]; Ministry of Education [20113402130010, PCSIRT IRT13038]; Anhui Project [08040102005]; National Institutes of Health [CA164133, DK56292, G12RR03034]; Central University [WK2340000032, WK2340000021] FX We thank Yunyu Shi for support and Martin Chalfie for input. This work was supported by Chinese 973 projects 2014CB964803, 2012CB945002, and 2010CB912103; Chinese Natural Science Foundation grants 31320103904, 314300054, 31271518, and 91313303; Chinese Academy of Science grant KSCX1-YW-R-65; MOST grant 2009DFA31010; Ministry of Education grants 20113402130010 and PCSIRT IRT13038; Anhui Project 08040102005; National Institutes of Health grants CA164133, DK56292, and G12RR03034; and Central University grants WK2340000032 and WK2340000021. NR 23 TC 12 Z9 13 U1 3 U2 24 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 15 PY 2014 VL 25 IS 25 BP 4166 EP 4173 DI 10.1091/mbc.E14-06-1133 PG 8 WC Cell Biology SC Cell Biology GA AX4TE UT WOS:000346923300016 PM 25355949 ER PT J AU Panagiotou, OA Wacholder, S AF Panagiotou, Orestis A. Wacholder, Sholom TI Invited Commentary: How Big Is That Interaction (in My Community)-and in Which Direction? SO AMERICAN JOURNAL OF EPIDEMIOLOGY LA English DT Editorial Material DE absolute risk; additive interaction; air pollution; intervention; lung cancer; public health; smoking ID ANTAGONISM; PREVENTION; SYNERGY AB In an accompanying article, Turner et al. (Am J Epidemiol. 2014; 180(12): 1145-1149) compare the joint effects of smoking and air pollution to make inferences about the reduction in lung cancer mortality achieved when reducing each exposure separately and when reducing both together. In this commentary, we use first principles to quantify the difference between the risk or mortality reduction obtained from reducing each of 2 exposures together and the sum of the risk differences obtained from reducing the 2 exposures separately. Metrics of the impact of joint effects or comparisons of joint effects presented in units of absolute risk, such as Rothman's I, can provide more meaningful quantitative measures of public health impact than unitless metrics (e.g., ratios) and standardized metrics (e.g., the population attributable fraction) of potential interventions for reducing smoking and air pollution exposure. In particular, the venerable attributable community risk metric can provide an estimate of the community impact of such interventions in units of absolute risk. A spreadsheet we provide demonstrates the calculation of the various metrics for hypothetical data similar to those reported by Turner et al. Using algebra, graphics, and examples, we show that positive interaction, or synergy, on the additive scale implies that the impact on risk reduction from a program that applies both interventions will be lesser than the sum of the impacts of the separate interventions. C1 [Panagiotou, Orestis A.; Wacholder, Sholom] NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. RP Wacholder, S (reprint author), NCI, Div Canc Epidemiol & Genet, 9609 Med Ctr Dr,Room 7E592, Bethesda, MD 20892 USA. EM wacholds@mail.nih.gov RI Panagiotou, Orestis/I-5934-2015 OI Panagiotou, Orestis/0000-0001-9604-8380 FU Intramural NIH HHS [Z99 CA999999] NR 13 TC 2 Z9 2 U1 0 U2 6 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0002-9262 EI 1476-6256 J9 AM J EPIDEMIOL JI Am. J. Epidemiol. PD DEC 15 PY 2014 VL 180 IS 12 BP 1150 EP 1158 DI 10.1093/aje/kwu279 PG 9 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA AW6ZN UT WOS:000346414300004 PM 25395027 ER PT J AU Louis, GMB Kannan, K Sapra, KJ Maisog, J Sundaram, R AF Louis, Germaine M. Buck Kannan, Kurunthachalam Sapra, Katherine J. Maisog, Jose Sundaram, Rajeshwari TI Urinary Concentrations of Benzophenone-Type Ultraviolet Radiation Filters and Couples' Fecundity SO AMERICAN JOURNAL OF EPIDEMIOLOGY LA English DT Article DE benzophenone; environment; fecundity; personal-care products; reproduction; sunscreen agents; time to pregnancy; ultraviolet light filters ID BISPHENOL-A CONCENTRATIONS; TANDEM MASS-SPECTROMETRY; YEAST 2-HYBRID ASSAY; UV FILTERS; DEVELOPMENTAL TOXICITY; REGRESSION-MODELS; PREGNANT-WOMEN; DERIVATIVES; FERTILITY; EXPOSURE AB Concern has arisen about benzophenone (BP) ultraviolet (UV) radiation filters, given their use in sunscreen and personal-care products and their reported estrogenic and antiandrogenic activity. We recruited 501 couples who were discontinuing use of contraceptives in order to become pregnant for the Longitudinal Investigation of Fertility and the Environment (LIFE) Study (Michigan and Texas, 2005-2009). Couples provided urine specimens and completed daily journals until they either achieved pregnancy or had tried for 12 months. Women used fertility monitors to time sexual intercourse and digital pregnancy tests. Urinary concentrations of 5 UV filters (ng/mL) were determined using triple-quadrupole mass spectrometry: 2,4-dihydroxybenzophenone (also called BP-1); 2,20,4,40-tetrahydroxybenzophenone (BP-2); 2-hydroxy-4-methoxybenzophenone (BP-3); 2,20-dihydroxy-4-methoxybenzophenone (BP-8); and 4-hydroxybenzophenone. Fecundability odds ratios were estimated for each UV filter (dichotomized at the 75th percentile) and adjusted for age, creatinine concentration, body mass index (weight (kg)/height (m)(2)), cotinine concentration, season, and site, while accounting for time off contraception. Separate models were fitted for each UV filter and partner; final models included partners' concentrations. Male partners' concentrations of BP-2 and 4-hydroxybenzophenone were associated with reduced fecundity in adjusted models (fecundability odds ratio (FOR) = 0.69 (95% confidence interval (CI): 0.50, 0.95) and FOR = 0.74 (95% CI: 0.54, 1.00), respectively). In models adjusting for both partners' concentrations, male BP-2 concentration remained associated with reduced fecundity (FOR = 0.69, 95% CI: 0.49, 0.97). These data suggest that male exposure to select UV filters may diminish couples' fecundity, resulting in a longer time to pregnancy. C1 [Louis, Germaine M. Buck; Sapra, Katherine J.] NICHD, Off Director, Div Intramural Populat Hlth Res, Rockville, MD USA. [Kannan, Kurunthachalam] New York State Dept Hlth, Wadsworth Ctr, Div Environm Hlth Sci, Albany, NY USA. [Kannan, Kurunthachalam] SUNY Albany, Sch Publ Hlth, Dept Environm Hlth Sci, Albany, NY 12222 USA. [Maisog, Jose] NICHD, Div Intramural Populat Hlth, Rockville, MD USA. [Sundaram, Rajeshwari] NICHD, Biostat & Bioinformat Branch, Div Intramural Populat Hlth Res, Rockville, MD USA. RP Louis, GMB (reprint author), Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Div Intramural Populat Hlth Res, 6100 Execut Blvd,Room 7B05, Rockville, MD 20852 USA. EM louisg@mail.nih.gov OI Sundaram, Rajeshwari/0000-0002-6918-5002; Buck Louis, Germaine/0000-0002-1774-4490 FU NICHD, National Institutes of Health [N01-HD-3-3355, N01-HD-3-3356, NOH-HD-3-3358, HHSN27500001] FX This work was funded by the Intramural Research Program of the NICHD, National Institutes of Health (contracts N01-HD-3-3355, N01-HD-3-3356, NOH-HD-3-3358, and HHSN27500001). NR 43 TC 12 Z9 12 U1 4 U2 17 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0002-9262 EI 1476-6256 J9 AM J EPIDEMIOL JI Am. J. Epidemiol. PD DEC 15 PY 2014 VL 180 IS 12 BP 1168 EP 1175 DI 10.1093/aje/kwu285 PG 8 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA AW6ZN UT WOS:000346414300006 ER PT J AU Zemp, FJ McKenzie, BA Lun, XQ Reilly, KM McFadden, G Yong, VW Forsyth, PA AF Zemp, Franz J. McKenzie, Brienne A. Lun, Xueqing Reilly, Karlyne M. McFadden, Grant Yong, V. Wee Forsyth, Peter A. TI Cellular Factors Promoting Resistance to Effective Treatment of Glioma with Oncolytic Myxoma Virus SO CANCER RESEARCH LA English DT Article ID HERPES-SIMPLEX-VIRUS; SIGNIFICANT ANTITUMOR-ACTIVITY; IMMUNOCOMPETENT ANIMAL-MODELS; MALIGNANT GLIOMAS; CEREBRAL-ISCHEMIA; IMMUNE-RESPONSES; GLIOBLASTOMA; VIROTHERAPY; CELLS; RAPAMYCIN AB Oncolytic virus therapy is being evaluated in clinical trials for human glioma. While it is widely assumed that the immune response of the patient to the virus infection limits the utility of the therapy, investigations into the specific cell type(s) involved in this response have been performed using nonspecific pharmacologic inhibitors or allogeneic models with compromised immunity. To identify the immune cells that participate in clearing an oncolytic infection in glioma, we used flow cytometry and immunohistochemistry to immunophenotype an orthotopic glioma model in immunocompetent mice after Myxoma virus (MYXV) administration. These studies revealed a large resident microglia and macrophage population in untreated tumors, and robust monocyte, T-, and NK cell infiltration 3 days after MYXV infection. To determine the role on the clinical utility of MYXV therapy for glioma, we used a combination of knockout mouse strains and specific immunocyte ablation techniques. Collectively, our experiments identify an important role for tumor-resident myeloid cells and overlapping roles for recruited NK and T cells in the clearance and efficacy of oncolytic MYXV from gliomas. Using a cyclophosphamide regimen to achieve lymphoablation prior and during MYXV treatment, we prevented treatment-induced peripheral immunocyte recruitment and, surprisingly, largely ablated the tumor- resident macrophage population. Virotherapy of cyclophosphamide-treated animals resulted in sustained viral infection within the glioma as well as a substantial survival advantage. This study demonstrates that resistance to MYXV virotherapy in syngeneic glioma models involves a multifaceted cellular immune response that can be overcome with cyclophosphamide-mediated lymphoablation. C1 [Zemp, Franz J.; McKenzie, Brienne A.; Lun, Xueqing; Forsyth, Peter A.] Univ Calgary, Southern Alberta Canc Res Inst, Calgary, AB T2N 1N4, Canada. [Zemp, Franz J.; McKenzie, Brienne A.; Lun, Xueqing; Forsyth, Peter A.] Univ Calgary, Clark H Smith Brain Tumor Ctr, Calgary, AB T2N 1N4, Canada. [Reilly, Karlyne M.] NCI, Mouse Canc Genet Program, Frederick, MD 21701 USA. [McFadden, Grant] Univ Florida, Coll Med, Mouse Canc Genet Program, Gainesville, FL USA. [Yong, V. Wee] Univ Calgary, Dept Clin Neurosci, Hotchkiss Brain Inst, Calgary, AB T2N 1N4, Canada. [Yong, V. Wee] Univ Calgary, Dept Oncol, Hotchkiss Brain Inst, Calgary, AB T2N 1N4, Canada. [Forsyth, Peter A.] Univ S Florida, Coll Med, H Lee Moffitt Canc Ctr & Res Inst, Dept Neurooncol, Tampa, FL 33612 USA. [Forsyth, Peter A.] Univ S Florida, Tampa, FL USA. RP Forsyth, PA (reprint author), Univ S Florida, Coll Med, H Lee Moffitt Canc Ctr & Res Inst, Dept Neurooncol, 12902 Magnolia Dr, Tampa, FL 33612 USA. EM Peter.Forsyth@moffitt.org FU Canadian Cancer Society Research Institute (CCSRI); Canadian Cancer Society; Terry Fox Foundation; V Foundation; Canadian Institutes of Health Research (CIHR); Alberta Innovates Health Solutions; CIHR; Izaak Walton Killam scholarship; NIH [R01 AI080607, R01 CA138541]; Intramural Research Program of NIH, NCI [ZIA BC 010541] FX This work was funded by the Canadian Cancer Society Research Institute (CCSRI) with funds raised by the Canadian Cancer Society (P.A. Forsyth), a Program Project Grant from the Terry Fox Foundation (P.A. Forsyth), the V Foundation (P.A. Forsyth), and the Canadian Institutes of Health Research (CIHR; V.W. Yong). During this work, F.J. Zemp was funded by Alberta Innovates Health Solutions, Vanier Scholarship from CIHR, and the Izaak Walton Killam scholarship. B.A. McKenzie was funded by CIHR. G. McFadden's laboratory is funded by NIH grants R01 AI080607 and R01 CA138541. K.M. Reilly's laboratory is funded by the Intramural Research Program of NIH, NCI (ZIA BC 010541). NR 48 TC 5 Z9 5 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 15 PY 2014 VL 74 IS 24 BP 7260 EP 7273 DI 10.1158/0008-5472.CAN-14-0876 PG 14 WC Oncology SC Oncology GA AW6FC UT WOS:000346363900013 PM 25336188 ER PT J AU Vire, B Skarzynski, M Thomas, JD Nelson, CG David, A Aue, G Burke, TR Rader, C Wiestner, A AF Vire, Berengere Skarzynski, Martin Thomas, Joshua D. Nelson, Christopher G. David, Alexandre Aue, Georg Burke, Terrence R., Jr. Rader, Christoph Wiestner, Adrian TI Harnessing the Fc mu Receptor for Potent and Selective Cytotoxic Therapy of Chronic Lymphocytic Leukemia SO CANCER RESEARCH LA English DT Article ID RELAPSED HODGKIN LYMPHOMA; HUMORAL IMMUNE-RESPONSES; LARGE-CELL LYMPHOMA; BRENTUXIMAB VEDOTIN; B-CELLS; TRASTUZUMAB EMTANSINE; MONOCLONAL-ANTIBODIES; TUMOR PROLIFERATION; BREAST-CANCER; IGM BINDING AB Chronic lymphocytic leukemia (CLL) is a B-cell malignancy in need of new, effective, and safe therapies. The recently identified IgM receptor Fc mu R is overexpressed on malignant B cells in CLL and mediates the rapid internalization and lysosomal shuttling of IgM via its Fc fragment (Fc mu). To exploit this internalization and trafficking pathway for targeted drug delivery, we engineered an IgM-derived protein scaffold (Fc mu) and linked it with the cytotoxic agent monomethylauristatin F. This Fc mu-drug conjugate was selectively toxic for Fc mu R-expressing cell lines in vitro and for CLL cells but not autologous normal T cells ex vivo. Notably, the cytotoxic activity of the Fcm-drug conjugate was maintained in CLL cells carrying a 17p deletion, which predicts resistance to standard chemotherapy. Next, we tested the possible therapeutic application of the Fc mu-drug conjugate in immunodeficient NOD/SCID/IL-2R gamma(null) (NSG) mice engrafted with peripheral blood cells from patients with leukemia. Three intravenous injections of the Fcm-drug conjugate over a 10-day period were well tolerated and selectively killed the human CLL cells but not the coengrafted autologous human T cells. In summary, we developed a novel strategy for targeted cytotoxic therapy of CLL based on the unique properties of Fc mu R. Fc mu R-targeted drug delivery showed potent and specific therapeutic activity in CLL, thus providing proof of concept for Fc mu R as a valuable therapeutic target in CLL and for IgM-based antibody-drug conjugates as a new targeting platform. C1 [Vire, Berengere; Skarzynski, Martin; Aue, Georg; Wiestner, Adrian] NHLBI, Hematol Branch, NIH, Bethesda, MD 20892 USA. [Thomas, Joshua D.; Nelson, Christopher G.; Burke, Terrence R., Jr.] NCI, Biol Chem Lab, Mol Discovery Program, Ctr Canc Res,NIH, Frederick, MD 21701 USA. [David, Alexandre] NIAID, Viral Dis Lab, NIH, Bethesda, MD 20892 USA. [Rader, Christoph] NCI, Expt Transplantat & Immunol Branch, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. [Rader, Christoph] Scripps Res Inst, Dept Canc Biol, Jupiter, FL USA. [Rader, Christoph] Scripps Res Inst, Dept Mol Therapeut, Jupiter, FL USA. RP Wiestner, A (reprint author), NHLBI, Hematol Branch, NIH, Bldg 10,CRC 3-5140,10 Ctr Dr, Bethesda, MD 20892 USA. EM crader@scripps.edu; wiestnera@mail.nih.gov RI Burke, Terrence/N-2601-2014 FU Intramural Research Programs of the National Heart, Lung, and Blood Institute and the National Cancer Institute, NIH [NIH U01, CA174844] FX This work was funded by the Intramural Research Programs of the National Heart, Lung, and Blood Institute and the National Cancer Institute, NIH, and by the NIH U01 grant CA174844. NR 49 TC 3 Z9 3 U1 1 U2 11 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD DEC 15 PY 2014 VL 74 IS 24 BP 7510 EP 7520 DI 10.1158/0008-5472.CAN-14-2030 PG 11 WC Oncology SC Oncology GA AW6FC UT WOS:000346363900034 PM 25344228 ER PT J AU Polascik, TJ Passoni, NM Villers, A Choyke, PL AF Polascik, Thomas J. Passoni, Niccolo' M. Villers, Arnauld Choyke, Peter L. TI Modernizing the Diagnostic and Decision-Making Pathway for Prostate Cancer SO CLINICAL CANCER RESEARCH LA English DT Article ID TRANSRECTAL ULTRASOUND BIOPSY; RADICAL PROSTATECTOMY; FUSION BIOPSY; MEN; ANTIGEN; MRI; CALCULATOR; SPECIMENS; OUTCOMES; TIME AB PSA has led to a drastic increase in the detection of prostate cancer, rendering this biomarker the gateway for the diagnostic pathway of prostatic neoplasms. However, the increase in incidence has not been mirrored by a similar reduction in mortality. Widespread PSA testing has facilitated the overdiagnosis and overtreatment of indolent disease. To reduce this phenomenon and avoid negative repercussions on the quality of life of men undergoing unnecessary therapies, the diagnostic pathway of prostate cancer needs to be improved. Multiparametric MRI (mp-MRI) can enhance the sensitivity and specificity of PSA, as well as the shortcomings of random biopsy sampling. This novel imaging technique has been proven to identify larger and more aggressive cancer foci, which should be targeted for treatment. New technological developments now allow for fusion of mp-MRI images with real-time ultrasound, opening the way to lesion-targeted biopsies. Furthermore, mp-MRI and targeted biopsies can also improve active surveillance protocols and permit more conservative focal therapy strategies. By implementing targeted biopsies, the diagnostic pathway will focus on clinically significant disease, consequently reducing overdiagnosis and overtreatment. Before this novel protocol becomes the new gold standard, mp-MRI acquisition and interpretation need to be standardized and targeted-biopsy strategies need to be further validated prior to abandoning random-sampling ones. Several multidisciplinary consortiums are already working on the standardization of prostate MRI, and there are ongoing prospective trials on targeted biopsies and MRI. Soon, imaging of prostatic lesions and selected biopsies will modify the diagnostic evaluation of prostate cancer, reducing overtreatment and therapy-derived complications that negatively affect quality of life. (C) 2014 AACR. C1 [Polascik, Thomas J.; Passoni, Niccolo' M.] Duke Univ, Med Ctr, Duke Canc Inst, Durham, NC USA. [Villers, Arnauld] Univ Lille Nord France, CHU Lille, Dept Urol, Lille, France. [Choyke, Peter L.] NCI, Mol Imaging Program, Ctr Canc Res, Bethesda, MD 20892 USA. RP Passoni, NM (reprint author), Duke Clin, Duke Canc Inst, Room 1080 Yellow Zone, Durham, NC 27710 USA. EM niccolo.passoni@gmail.com RI Arnauld, VILLERS/K-6629-2016 OI Arnauld, VILLERS/0000-0002-6298-7758 NR 32 TC 7 Z9 8 U1 1 U2 1 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1078-0432 EI 1557-3265 J9 CLIN CANCER RES JI Clin. Cancer Res. PD DEC 15 PY 2014 VL 20 IS 24 BP 6254 EP 6257 DI 10.1158/1078-0432.CCR-14-0247 PG 4 WC Oncology SC Oncology GA AW7AZ UT WOS:000346418100006 PM 25316814 ER PT J AU Anderson, AA Smith, E Chernomordik, V Ardeshirpour, Y Chowdhry, F Thurm, A Black, D Matthews, D Rennert, O Gandjbakhche, AH AF Anderson, Afrouz A. Smith, Elizabeth Chernomordik, Victor Ardeshirpour, Yasaman Chowdhry, Fatima Thurm, Audrey Black, David Matthews, Dennis Rennert, Owen Gandjbakhche, Amir H. TI Prefrontal cortex hemodynamics and age: a pilot study using functional near infrared spectroscopy in children SO FRONTIERS IN NEUROSCIENCE LA English DT Article DE functional near infrared spectroscopy; autoregulation; hemodynamic model ID CEREBRAL-BLOOD-FLOW; BRAIN ACTIVATION; AUTOREGULATION; FREQUENCY; OSCILLATIONS; METHODOLOGY; METABOLISM; DEPENDENCE; PERFUSION; PRESSURE AB Cerebral hemodynamics reflect cognitive processes and underlying physiological processes, both of which are captured by functional near infrared spectroscopy (fNIRS). Here, we introduce a novel parameter of Oxygenation Variability directly obtained from fNIRS data -the OV Index-and we demonstrate its use in children. fNIRS data were collected from 17 children (ages 4-8 years), while they performed a standard Go/No-Go task. Data were analyzed using two frequency bands-the first attributed to cerebral autoregulation (CA) (< 0.1 Hz) and the second to respiration (0.2-0.3 Hz). Results indicate differences in variability of oscillations of oxygen saturation (SO2) between the two different bands. These pilot data reveal a dynamic relationship between chronological age and OV index in CA associated frequency of < 0.1 Hz. Specifically, OV index increased with age between 4 and 6 years. In addition, there was much higher variability in frequencies associated with CA than for respiration across subjects. These findings provide preliminary evidence for the utility of the OV index and are the first to describe the relationship between cerebral autoregulation and age in children using fNIRS methodology. C1 [Anderson, Afrouz A.; Chernomordik, Victor; Ardeshirpour, Yasaman; Chowdhry, Fatima; Rennert, Owen; Gandjbakhche, Amir H.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, NIH, Bethesda, MD 20814 USA. [Anderson, Afrouz A.] Univ Calif Davis, Dept Biomed Engn, Davis, CA 95616 USA. [Smith, Elizabeth; Thurm, Audrey; Black, David] NIMH, Bethesda, MD 20892 USA. [Matthews, Dennis] Univ Calif Davis, Sch Med, Dept Neurol Surg, Davis, CA 95616 USA. RP Gandjbakhche, AH (reprint author), Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, NIH, BG 9 RM 1E116,9 Mem Dr, Bethesda, MD 20814 USA. EM gandjbaa@mail.nih.gov FU National Institute of Mental Health and Eunice Kennedy Shriver National Institute of Child Health and Human Development; NIMH [2013-M-0007] FX We thank the families that dedicated their time to make this research happen. This research was supported by the Intramural Program of the National Institute of Mental Health and Eunice Kennedy Shriver National Institute of Child Health and Human Development and was completed as part of NIMH protocol 2013-M-0007. NR 37 TC 1 Z9 1 U1 3 U2 7 PU FRONTIERS RESEARCH FOUNDATION PI LAUSANNE PA PO BOX 110, LAUSANNE, 1015, SWITZERLAND SN 1662-453X J9 FRONT NEUROSCI-SWITZ JI Front. Neurosci. PD DEC 15 PY 2014 VL 8 AR UNSP 393 DI 10.3389/fnins.2014.00393 PG 7 WC Neurosciences SC Neurosciences & Neurology GA AW9EO UT WOS:000346560500001 PM 25565935 ER PT J AU Nakamura, T Yoshitomi, Y Sakai, K Patel, V Fukumoto, S Yamada, Y AF Nakamura, Takashi Yoshitomi, Yasuo Sakai, Kiyoshi Patel, Vyomesh Fukumoto, Satoshi Yamada, Yoshihiko TI Epiprofin orchestrates epidermal keratinocyte proliferation and differentiation SO JOURNAL OF CELL SCIENCE LA English DT Article DE Sp transcription factor; Skin development; Proliferation; Differentiation; Keratinocyte; Transit amplifying cell; Stem cell; p63; Notch ID TRANSIT-AMPLIFYING CELLS; STEM-CELLS; RETINOBLASTOMA PROTEIN; TUMOR-SUPPRESSOR; EPITHELIAL DEVELOPMENT; TRANSCRIPTION FACTORS; NEGATIVE REGULATION; NOTCH; LRIG1; EXPRESSION AB The basal layer of the epidermis contains stem cells and transit amplifying cells that rapidly proliferate and differentiate further into the upper layers of the epidermis. A number of molecules have been identified as regulators of this process, including p63 (also known as tumor protein 63) and Notch1. However, little is known about the mechanisms that regulate the transitions from stem cell to proliferating or differentiating transit amplifying cell. Here, we demonstrate that epiprofin (Epfn, also known as Sp6) plays crucial distinct roles in these transition stages as a cell cycle regulator and a transcription factor. Epfn knockout mice have a thickened epidermis, in which p63-expressing basal cells form multiple layers owing to the accumulation of premature transit amplifying cells with reduced proliferation and a reduction in the number of differentiating keratinocytes expressing Notch1. We found that low levels of Epfn expression increased the proliferation of human immortalized keratinocyte (HaCaT) cells by increasing EGF responsiveness and superphosphorylation of Rb. By contrast, high levels of Epfn expression promoted cell cycle exit and differentiation, by reducing E2F transactivation and inducing Notch1 expression. Our findings identify multiple novel functions of Epfn in epidermal development. C1 [Nakamura, Takashi; Fukumoto, Satoshi] Tohoku Univ, Grad Sch Dent, Dept Oral Hlth & Dev Sci, Div Pediat Dent, Sendai, Miyagi 9808575, Japan. [Nakamura, Takashi] Tohoku Univ, Grad Sch Dent, Liaison Ctr Innovat Dent, Sendai, Miyagi 9808575, Japan. [Nakamura, Takashi; Yoshitomi, Yasuo; Sakai, Kiyoshi; Yamada, Yoshihiko] Natl Inst Dent & Craniofacial Res, Lab Cell & Dev Biol, NIH, Bethesda, MD 20892 USA. [Patel, Vyomesh] Natl Inst Dent & Craniofacial Res, Oral & Pharyngeal Canc Branch, NIH, Bethesda, MD 20892 USA. RP Nakamura, T (reprint author), Tohoku Univ, Grad Sch Dent, Dept Oral Hlth & Dev Sci, Div Pediat Dent, Sendai, Miyagi 9808575, Japan. EM taka@dent.tohoku.ac.jp; yoshi.yamada@nih.gov RI Nakamura, Takashi/P-7796-2016 OI Nakamura, Takashi/0000-0001-9904-1037 FU Intramural Research Program of the National Institutes of Health, National Institute of Dental and Craniofacial Research [DE000483-26, DE000720-08]; Ministry of Education, Science and Culture of Japan [24390441, 24659908]; NEXT program [LS010]; Japan Society for the Promotion of Science FX This work was supported in part by the Intramural Research Program of the National Institutes of Health, National Institute of Dental and Craniofacial Research [grant numbers DE000483-26 and DE000720-08 to Y.Yamada]; and grants-in-aid [grant numbers 24390441 and 24659908 to T.N.] from the Ministry of Education, Science and Culture of Japan; and the NEXT program [grant number LS010 to S.F.]; as well as a fellowship from the Japan Society for the Promotion of Science (to T.N. and Y.Yoshitomi). Deposited in PMC for release after 12 months. NR 54 TC 6 Z9 6 U1 0 U2 3 PU COMPANY OF BIOLOGISTS LTD PI CAMBRIDGE PA BIDDER BUILDING CAMBRIDGE COMMERCIAL PARK COWLEY RD, CAMBRIDGE CB4 4DL, CAMBS, ENGLAND SN 0021-9533 EI 1477-9137 J9 J CELL SCI JI J. Cell Sci. PD DEC 15 PY 2014 VL 127 IS 24 BP 5261 EP 5272 DI 10.1242/jcs.156778 PG 12 WC Cell Biology SC Cell Biology GA AW6WF UT WOS:000346405500013 PM 25344255 ER PT J AU Nakagawa, M Schmitz, R Xiao, WM Goldman, CK Xu, WH Yang, YD Yu, X Waldmann, TA Staudt, LM AF Nakagawa, Masao Schmitz, Roland Xiao, Wenming Goldman, Carolyn K. Xu, Weihong Yang, Yandan Yu, Xin Waldmann, Thomas A. Staudt, Louis M. TI Gain-of-function CCR4 mutations in adult T cell leukemia/lymphoma SO JOURNAL OF EXPERIMENTAL MEDICINE LA English DT Article ID MACROPHAGE-DERIVED CHEMOKINE; CLINICAL-SIGNIFICANCE; LEUKEMIA-LYMPHOMA; WHIM-SYNDROME; RECEPTOR 4; IN-VITRO; EXPRESSION; CXCR4; LIGAND; ACTIVATION AB Adult T cell leukemia/lymphoma (ATLL) is an aggressive malignancy caused by human T cell lymphotropic virus type-I (HTLV-I) without curative treatment at present. To illuminate the pathogenesis of ATLL we performed whole transcriptome sequencing of purified ATLL patient samples and discovered recurrent somatic mutations in CCR4, encoding CC chemokine receptor 4. CCR4 mutations were detected in 14/53 ATLL samples (26%) and consisted exclusively of nonsense or frameshift mutations that truncated the coding region at C329, Q330, or Y331 in the carboxy terminus. Functionally, the CCR4-Q330 nonsense isoform was gain-of-function because it increased cell migration toward the CCR4 ligands CCL17 and CCL22, in part by impairing receptor internalization. This mutant enhanced PI(3) kinase/AKT activation after receptor engagement by CCL22 in ATLL cells and conferred a growth advantage in long-term in vitro cultures. These findings implicate somatic gain-of-function CCR4 mutations in the pathogenesis of ATLL and suggest that inhibition of CCR4 signaling might have therapeutic potential in this refractory malignancy. C1 [Nakagawa, Masao; Schmitz, Roland; Xiao, Wenming; Goldman, Carolyn K.; Xu, Weihong; Yang, Yandan; Yu, Xin; Waldmann, Thomas A.; Staudt, Louis M.] NCI, Lymphoid Malignancies Branch, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. RP Staudt, LM (reprint author), NCI, Lymphoid Malignancies Branch, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. EM lstaudt@mail.nih.gov FU Intramural Research Program of the National Institutes of Health, National Cancer Institute, Center for Cancer Research; Dr. Mildred Scheel Stiftung fur Krebsforschug (Deutsche Krebshilfe) FX This research was supported by the Intramural Research Program of the National Institutes of Health, National Cancer Institute, Center for Cancer Research. Roland Schmitz was supported by the Dr. Mildred Scheel Stiftung fur Krebsforschung (Deutsche Krebshilfe) NR 31 TC 25 Z9 25 U1 1 U2 8 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 950 THIRD AVE, 2ND FLR, NEW YORK, NY 10022 USA SN 0022-1007 EI 1540-9538 J9 J EXP MED JI J. Exp. Med. PD DEC 15 PY 2014 VL 211 IS 13 BP 2497 EP 2505 DI 10.1084/jem.20140987 PG 9 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA AW6FW UT WOS:000346366100002 PM 25488980 ER PT J AU Lucas, CL Zhang, Y Venida, A Wang, Y Hughes, J McElwee, J Butrick, M Matthews, H Price, S Biancalana, M Wang, XC Richards, M Pozos, T Barlan, I Ozen, A Rao, VK Su, HC Lenardo, MJ AF Lucas, Carrie L. Zhang, Yu Venida, Anthony Wang, Ying Hughes, Jason McElwee, Joshua Butrick, Morgan Matthews, Helen Price, Susan Biancalana, Matthew Wang, Xiaochuan Richards, Michael Pozos, Tamara Barlan, Isil Ozen, Ahmet Rao, V. Koneti Su, Helen C. Lenardo, Michael J. TI Heterozygous splice mutation in PIK3R1 causes human immunodeficiency with lymphoproliferation due to dominant activation of PI3K SO JOURNAL OF EXPERIMENTAL MEDICINE LA English DT Article ID B-CELL MALIGNANCIES; PHOSPHOINOSITIDE 3-KINASE; REGULATORY SUBUNIT; CATALYTIC SUBUNIT; SOMATIC MUTATIONS; P85-ALPHA SUBUNIT; IDELALISIB; P110-ALPHA; INHIBITOR; P110-DELTA AB Class IA phosphatidylinositol 3-kinases (PI3K), which generate PIP3 as a signal for cell growth and proliferation, exist as an intracellular complex of a catalytic subunit bound to a regulatory subunit. We and others have previously reported that heterozygous mutations in PIK3CD encoding the p110 delta catalytic PI3K subunit cause a unique disorder termed p110 delta activating mutations causing senescent T cells, lymphadenopathy, and immunodeficiency (PASLI) disease. We report four patients from three families with a similar disease who harbor a recently reported heterozygous splice site mutation in PIK3R1, which encodes the p85 alpha, p55 alpha, and p50 alpha regulatory PI3K subunits. These patients suffer from recurrent sinopulmonary infections and lymphoproliferation, exhibit hyperactive PI3K signaling, and have prominent expansion and skewing of peripheral blood CD8(+) T cells toward terminally differentiated senescent effector cells with short telomeres. The PIK3R1 splice site mutation causes skipping of an exon, corresponding to loss of amino acid residues 434-475 in the inter-SH2 domain. The mutant p85. protein is expressed at low levels in patient cells and activates PI3K signaling when overexpressed in T cells from healthy subjects due to qualitative and quantitative binding changes in the p85 alpha-p110 delta complex and failure of the C-terminal region to properly inhibit p110 delta catalytic activity. C1 [Lucas, Carrie L.; Venida, Anthony; Matthews, Helen; Price, Susan; Biancalana, Matthew; Rao, V. Koneti; Lenardo, Michael J.] NIAID, Mol Dev Immune Syst Sect, Immunol Lab, NIH, Bethesda, MD 20892 USA. [Lucas, Carrie L.; Zhang, Yu; Venida, Anthony; Butrick, Morgan; Matthews, Helen; Price, Susan; Biancalana, Matthew; Rao, V. Koneti; Su, Helen C.; Lenardo, Michael J.] NIAID, NIAID Clin Genom Program, NIH, Bethesda, MD 20892 USA. [Zhang, Yu; Su, Helen C.] NIAID, Human Immunol Dis Unit, Host Def Lab, NIH, Bethesda, MD 20892 USA. [Butrick, Morgan] NIAID, Intramural Clin Management & Operat Branch, NIH, Bethesda, MD 20892 USA. [Wang, Ying; Wang, Xiaochuan] Fudan Univ, Dept Clin Immunol, Childrens Hosp, Shanghai 200433, Peoples R China. [Hughes, Jason; McElwee, Joshua] Merck & Co Inc, Merck Res Labs, Boston, MA 02115 USA. RP Lenardo, MJ (reprint author), NIAID, Mol Dev Immune Syst Sect, Immunol Lab, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA. EM lenardo@nih.gov RI Su, Helen/H-9541-2015 OI Su, Helen/0000-0002-5582-9110 FU Intramural NIH HHS NR 37 TC 39 Z9 40 U1 3 U2 18 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 950 THIRD AVE, 2ND FLR, NEW YORK, NY 10022 USA SN 0022-1007 EI 1540-9538 J9 J EXP MED JI J. Exp. Med. PD DEC 15 PY 2014 VL 211 IS 13 BP 2537 EP 2547 DI 10.1084/jem.20141759 PG 11 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA AW6FW UT WOS:000346366100005 PM 25488983 ER PT J AU Zhang, Q Dove, CG Hor, JL Murdock, HM Strauss-Albee, DM Garcia, JA Mandl, JN Grodick, RA Jing, H Chandler-Brown, DB Lenardo, TE Crawford, G Matthews, HF Freeman, AF Cornall, RJ Germain, RN Mueller, SN Su, HC AF Zhang, Qian Dove, Christopher G. Hor, Jyh Liang Murdock, Heardley M. Strauss-Albee, Dara M. Garcia, Jordan A. Mandl, Judith N. Grodick, Rachael A. Jing, Huie Chandler-Brown, Devon B. Lenardo, Timothy E. Crawford, Greg Matthews, Helen F. Freeman, Alexandra F. Cornall, Richard J. Germain, Ronald N. Mueller, Scott N. Su, Helen C. TI DOCK8 regulates lymphocyte shape integrity for skin antiviral immunity SO JOURNAL OF EXPERIMENTAL MEDICINE LA English DT Article ID HERPES-SIMPLEX-VIRUS; WISKOTT-ALDRICH-SYNDROME; CD8(+) T-CELLS; VARICELLA-ZOSTER-VIRUS; NATURAL-KILLER-CELLS; SYNDROME PROTEIN; LEUKOCYTE MIGRATION; DENDRITIC CELLS; IMMUNOLOGICAL SYNAPSES; NEUTROPHIL CHEMOTAXIS AB DOCK8 mutations result in an inherited combined immunodeficiency characterized by increased susceptibility to skin and other infections. We show that when DOCK8-deficient T and NK cells migrate through confined spaces, they develop cell shape and nuclear deformation abnormalities that do not impair chemotaxis but contribute to a distinct form of catastrophic cell death we term cytothripsis. Such defects arise during lymphocyte migration in collagen-dense tissues when DOCK8, through CDC42 and p21-activated kinase (PAK), is unavailable to coordinate cytoskeletal structures. Cytothripsis of DOCK8-deficient cells prevents the generation of long-lived skin-resident memory CD8 T cells, which in turn impairs control of herpesvirus skin infections. Our results establish that DOCK8-regulated shape integrity of lymphocytes prevents cytothripsis and promotes antiviral immunity in the skin. C1 [Zhang, Qian; Dove, Christopher G.; Murdock, Heardley M.; Strauss-Albee, Dara M.; Garcia, Jordan A.; Grodick, Rachael A.; Jing, Huie; Chandler-Brown, Devon B.; Lenardo, Timothy E.; Su, Helen C.] NIAID, Host Def Lab, NIH, Bethesda, MD 20892 USA. [Mandl, Judith N.; Germain, Ronald N.] NIAID, Lab Syst Biol, NIH, Bethesda, MD 20892 USA. [Matthews, Helen F.] NIAID, Immunol Lab, NIH, Bethesda, MD 20892 USA. [Freeman, Alexandra F.] NIAID, Lab Clin Infect Dis, NIH, Bethesda, MD 20892 USA. [Hor, Jyh Liang; Mueller, Scott N.] Univ Melbourne, Dept Microbiol & Immunol, Peter Doherty Inst Infect & Immun, Melbourne, Vic 3010, Australia. [Hor, Jyh Liang; Mueller, Scott N.] Univ Melbourne, ARC Ctr Excellence Adv Mol Imaging, Melbourne, Vic 3010, Australia. [Crawford, Greg; Cornall, Richard J.] Univ Oxford, Nuffield Dept Med, MRC Human Immunol Unit, Oxford OX3 7BN, England. RP Su, HC (reprint author), NIAID, Host Def Lab, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA. EM smue@unimelb.edu.au; hsu@niaid.nih.gov RI Su, Helen/H-9541-2015; Mueller, Scott/B-1918-2012; OI Su, Helen/0000-0002-5582-9110; Mueller, Scott/0000-0002-3838-3989; Zhang, Qian/0000-0002-9040-3289 FU Intramural Research Program of the NIAID; NIH; Australian Research Council; Medical Research Council UK; Oxford NIHR Biomedical Research Centre FX This work was supported by the Intramural Research Program of the NIAID, NIH, the Australian Research Council (S.N. Mueller), the Medical Research Council UK (R.J. Cornall), and the Oxford NIHR Biomedical Research Centre (R.J. Cornall). R.A. Grodick was an HHMI-NIH Research Scholar. NR 79 TC 24 Z9 24 U1 3 U2 7 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 950 THIRD AVE, 2ND FLR, NEW YORK, NY 10022 USA SN 0022-1007 EI 1540-9538 J9 J EXP MED JI J. Exp. Med. PD DEC 15 PY 2014 VL 211 IS 13 BP 2549 EP 2566 DI 10.1084/jem.20141307 PG 18 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA AW6FW UT WOS:000346366100006 PM 25422492 ER PT J AU Gao, P Han, XJ Zhang, Q Yang, ZQ Fuss, IJ Myers, TG Gardina, PJ Zhang, FP Strober, W AF Gao, Ping Han, Xiaojuan Zhang, Qi Yang, Zhiqiong Fuss, Ivan J. Myers, Timothy G. Gardina, Paul J. Zhang, Fuping Strober, Warren TI Dynamic changes in E-protein activity regulate T reg cell development SO JOURNAL OF EXPERIMENTAL MEDICINE LA English DT Article ID FOXP3 TRANSCRIPTION-FACTOR; LOOP-HELIX PROTEINS; NF-KAPPA-B; DIFFERENTIAL REQUIREMENT; LYMPHOCYTE DEVELOPMENT; RECEPTOR; ACTIVATION; ID3; MODULATION; EXPRESSION AB E-proteins are TCR-sensitive transcription factors essential for intrathymic T cell transitions. Here, we show that deletion of E-proteins leads to both enhanced peripheral TGF-beta-induced regulatory T (iT reg) cell and thymic naturally arising T reg cell (nT reg cell) differentiation. In contrast, deletion of Id proteins results in reduced nT reg cell differentiation. Mechanistic analysis indicated that decreased E-protein activity leads to de-repression of signaling pathways that are essential to Foxp3 expression. Decreased E-protein binding to an IL-2R alpha enhancer locus facilitated TCR-induced IL-2R alpha expression. Similarly, decreased E-protein activity facilitated TCR-induced NF-kappa B activation and generation of c-Rel. Consistent with this, microarray analysis indicated that cells with E-protein depletion that are not yet expressing Foxp3 exhibit activation of the IL-2 and NF-kappa B signaling pathways as well as enhanced expression of many of the genes associated with Foxp3 induction. Finally, studies using Nur77-GFP mice to monitor TCR signaling showed that TCR signaling strength sufficient to induce Foxp3 differentiation is accompanied by down-regulation of E-protein levels. Collectively, these data suggest that TCR stimulation acts in part through down-regulation of E-protein activity to induce T reg cell lineage development. C1 [Gao, Ping; Han, Xiaojuan; Zhang, Qi; Zhang, Fuping] Chinese Acad Sci, Inst Microbiol, CAS Key Lab Pathogen Microbiol & Immunol, Beijing 100101, Peoples R China. [Yang, Zhiqiong; Fuss, Ivan J.; Strober, Warren] NIAID, Mucosal Immun Sect, Host Def Lab, NIH, Bethesda, MD 20892 USA. [Myers, Timothy G.; Gardina, Paul J.] NIAID, Genom Technol Sect, Res Technol Branch, NIH, Bethesda, MD 20892 USA. RP Zhang, FP (reprint author), Chinese Acad Sci, Inst Microbiol, CAS Key Lab Pathogen Microbiol & Immunol, Beijing 100101, Peoples R China. EM zhangfp@im.ac.cn; wstrober@niaid.nih.gov FU National Natural science Foundation of China [31270933]; Ministry of Health of China [2013ZX10004608]; Intramural Research Program of National Institute of Allergy and Infectious Diseases FX This work was supported by National Natural science Foundation of China (31270933, F. Zhang), Ministry of Health of China (2013ZX10004608, F. Zhang), and Intramural Research Program of National Institute of Allergy and Infectious Diseases (W. Strober). NR 35 TC 5 Z9 5 U1 1 U2 3 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 950 THIRD AVE, 2ND FLR, NEW YORK, NY 10022 USA SN 0022-1007 EI 1540-9538 J9 J EXP MED JI J. Exp. Med. PD DEC 15 PY 2014 VL 211 IS 13 BP 2651 EP 2668 DI 10.1084/jem.20132681 PG 18 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA AW6FW UT WOS:000346366100012 PM 25488982 ER PT J AU Wilhelm, CM Snider, TH Babin, MC Jett, DA Platoff, GE Yeung, DT AF Wilhelm, Christina M. Snider, Thomas H. Babin, Michael C. Jett, David A. Platoff, Gennady E., Jr. Yeung, David T. TI A comprehensive evaluation of the efficacy of leading oxime therapies in guinea pigs exposed to organophosphorus chemical warfare agents or pesticides SO TOXICOLOGY AND APPLIED PHARMACOLOGY LA English DT Article DE Oxime; Efficacy; Guinea pig; Intramuscular; Toxicity ID IN-VIVO REACTIVATION; NERVE AGENTS; INHIBITED ACETYLCHOLINESTERASE; PHOSPHYLATED CHOLINESTERASES; PYRIDINIUM OXIMES; HYDROXAMIC ACIDS; SARIN; TABUN; CYCLOSARIN; BRAIN AB The currently fielded pre-hospital therapeutic regimen for the treatment of organophosphorus (OP) poisoning in the United States (U.S.) is the administration of atropine in combination with an oxime antidote (2-PAM Cl) to reactivate inhibited acetylcholinesterase (AChE). Depending on clinical symptoms, an anticonvulsant, e.g., diazepam, may also be administered. Unfortunately, 2-PAM Cl does not offer sufficient protection across the range of OP threat agents, and there is some question as to whether it is the most effective oxime compound available. The objective of the present study is to identify an oxime antidote, under standardized and comparable conditions, that offers protection at the FDA approved human equivalent dose (HED) of 2-PAM Cl against tabun (GA), satin (GB), soman (GD), cyclosarin (GF), and VX, and the pesticides paraoxon, chlorpyrifos oxon, and phorate oxon. Male Hartley guinea pigs were subcutaneously challenged with a lethal level of OP and treated at approximately 1 min post challenge with atropine followed by equimolar oxime therapy (2-PAM Cl, HI-6 DMS, obidoxime Cl-2, TMB-4, MMB4-DMS, HLo-7 DMS, MINA, and RS194B) or therapeutic-index (TI) level therapy (HI-6 DMS, MMB4-DMS, MINA, and RS194B). Clinical signs of toxicity were observed for 24 h post challenge and blood cholinesterase [AChE and butyrylcholinesterase (BChE)] activity was analyzed utilizing a modified Ellman's method. When the oxime is standardized against the HED of 2-PAM Cl for guinea pigs, the evidence from clinical observations, lethality, quality of life (QOL) scores, and cholinesterase reactivation rates across all OPs indicated that MMB4 DMS and HLo-7 DMS were the two most consistently efficacious oximes. (C) 2014 The Authors. Published by Elsevier Inc. C1 [Wilhelm, Christina M.; Snider, Thomas H.; Babin, Michael C.] Battelle Mem Inst, Columbus, OH 43201 USA. [Jett, David A.; Yeung, David T.] NINDS, NIH, Bethesda, MD 20892 USA. [Platoff, Gennady E., Jr.] NIAID, NIH, Bethesda, MD 20892 USA. RP Wilhelm, CM (reprint author), Battelle Mem Inst, 505 King Ave,JM-7, Columbus, OH 43201 USA. EM wilhelmc@battelle.org; snidert@battelle.org; babinm@battelle.org; jettd@ninds.nih.gov; platoffg@niaid.nih.gov; dy70v@nih.gov OI Snider, Thomas/0000-0001-5673-2903; /0000-0001-5692-0170 FU National Institutes of Health (NIH) [Y1-OD-0387-01]; NIH; NIAID; National Institute of Neurological Disorders and Stroke (NINDS); DoD Defense Technical Information Center (DTIC) under the Chemical, Biological, Radiological & Nuclear Defense Information Analysis Center (CBRNIAC) program [SP0700-00-D-3180, 0687, 832/CB-IO-OOI2] FX This work was supported by the National Institutes of Health (NIH) Office of the Director through an interagency agreement (OD#: Y1-OD-0387-01) between the National Institute of Allergy and Infectious Diseases (NIAID) and Department of Defense (DoD) and prepared under the auspices of the NIH, NIAID, National Institute of Neurological Disorders and Stroke (NINDS), and the DoD Defense Technical Information Center (DTIC) under the Chemical, Biological, Radiological & Nuclear Defense Information Analysis Center (CBRNIAC) program, Contract No. SP0700-00-D-3180, Delivery Order Number 0687, CBRNIAC Task 832/CB-IO-OOI2. NR 61 TC 14 Z9 15 U1 5 U2 57 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 15 PY 2014 VL 281 IS 3 BP 254 EP 265 DI 10.1016/j.taap.2014.10.009 PG 12 WC Pharmacology & Pharmacy; Toxicology SC Pharmacology & Pharmacy; Toxicology GA AW7QX UT WOS:000346460700002 PM 25448441 ER PT J AU Eldridge, SR Covey, J Morris, J Fang, BL Horn, TL Elsass, KE Hamre, JR McCormick, DL Davis, MA AF Eldridge, Sandy R. Covey, Joseph Morris, Joel Fang, Bingliang Horn, Thomas L. Elsass, Karen E. Hamre, John R., III McCormick, David L. Davis, Myrtle A. TI Characterization of acute biliary hyperplasia in Fisher 344 Rats administered the Indole-3-Carbinol Analog, NSC-743380 SO TOXICOLOGY AND APPLIED PHARMACOLOGY LA English DT Article DE Hepatotoxicity; Biliary hyperplasia; Rat liver; Indole-3-carbinol ID LIVER; CHOLANGIOCYTES; PROLIFERATION AB NSC-743380 (1-[(3-chlorophenyl)-methyl]-1H-indole-3-carbinol) is in early stages of development as an anticancer agent Two metabolites reflect sequential conversion of the carbinol functionality to a carboxaldehyde and the major metabolite, 1-[(3-chlorophenyl)-methyl]-1H-indole-3-carboxylic acid. In an exploratory toxicity study in rats, NSC-743380 induced elevations in liver-associated serum enzymes and biliary hyperplasia. Biliaty hyperplasia was observed 2 days after dosing orally for 2 consecutive days at 100 mg/kg/day. Notably, hepatotoxicity and biliaty hyperplasia were observed after oral administration of the parent compound, but not when major metabolites were administered. The toxicities of a structurally similar but pharmacologically inactive molecule and a structurally diverse molecule with a similar efficacy profile in killing cancer cells in vitro were compared to NSC-743380 to explore scaffold versus target-mediated toxicity. Following two oral doses of 100 mg/kg/day given once daily on two consecutive days, the structurally unrelated active compound produced hepatic toxicity similar to NSC-743380. The structurally similar inactive compound did not, but, lower exposures were achieved. The weight of evidence implies that the hepatotoxicity associated with NSC-743380 is related to the anticancer activity of the parent molecule. Furthermore, because biliary hyperplasia represents an unmanageable and non-monitorable adverse effect in clinical settings, this model may provide an opportunity for investigators to use a short-duration study design to explore biomarkers of biliary hyperplasia. Published by Elsevier Inc. C1 [Eldridge, Sandy R.; Covey, Joseph; Morris, Joel; Davis, Myrtle A.] NCI, Dev Therapeut Program, Div Canc Treatment & Diag, Rockville, MD 20892 USA. [Horn, Thomas L.; McCormick, David L.] IIT, Res Inst, Chicago, IL 60616 USA. [Elsass, Karen E.] Battelle Columbus, Columbus, OH 43201 USA. [Hamre, John R., III] Leidos Biomed Res Inc, Frederick Natl Lab Canc Res, Invest Toxicol Lab, Frederick, MD 21702 USA. [Fang, Bingliang] Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA. RP Eldridge, SR (reprint author), NCI, Dev Therapeut Program, Div Canc Treatment & Diag, Rockville, MD 20892 USA. EM myrtledavis@mail.nih.gov FU Developmental Therapeutics Program in the Division of Cancer Treatment and Diagnosis of the National Cancer Institute; National Cancer Institute, National Institutes of Health [HHSN261200800001E, N01-CM-201100019, N01-CM-201100027] FX The authors declared no potential conflicts of interest with respect to the authorship and/or publication of this article. The content of this publication does not necessarily reflect the views or policies of the Department of Health and Human Services, nor does mention of trade names, commercial products, or organizations imply endorsement by the U.S. Government. This research was supported [in part] by the Developmental Therapeutics Program in the Division of Cancer Treatment and Diagnosis of the National Cancer Institute and with federal funds from the National Cancer Institute, National Institutes of Health, under Contracts No. HHSN261200800001E, N01-CM-201100019 and N01-CM-201100027. NR 15 TC 2 Z9 2 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 0041-008X EI 1096-0333 J9 TOXICOL APPL PHARM JI Toxicol. Appl. Pharmacol. PD DEC 15 PY 2014 VL 281 IS 3 BP 303 EP 309 DI 10.1016/j.taap.2014.10.015 PG 7 WC Pharmacology & Pharmacy; Toxicology SC Pharmacology & Pharmacy; Toxicology GA AW7QX UT WOS:000346460700007 PM 25448049 ER PT J AU Sheetlin, SL Park, Y Frith, MC Spouge, JL AF Sheetlin, Sergey L. Park, Yonil Frith, Martin C. Spouge, John L. TI Frameshift alignment: statistics and post-genomic applications SO BIOINFORMATICS LA English DT Article ID LOCAL ALIGNMENT; SCORE DISTRIBUTIONS; SIMILARITY SEARCH; PROTEIN SEQUENCES; DNA-SEQUENCES; GENERATION; ERRORS; MUTATIONS; BLAST; TOOL AB Motivation: The alignment of DNA sequences to proteins, allowing for frameshifts, is a classic method in sequence analysis. It can help identify pseudogenes (which accumulate mutations), analyze raw DNA and RNA sequence data (which may have frameshift sequencing errors), investigate ribosomal frameshifts, etc. Often, however, only ad hoc approximations or simulations are available to provide the statistical significance of a frameshift alignment score. Results: We describe a method to estimate statistical significance of frameshift alignments, similar to classic BLAST statistics. (BLAST presently does not permit its alignments to include frameshifts.) We also illustrate the continuing usefulness of frameshift alignment with two 'post-genomic' applications: (i) when finding pseudogenes within the human genome, frameshift alignments show that most anciently conserved non-coding human elements are recent pseudogenes with conserved ancestral genes; and (ii) when analyzing metagenomic DNA reads from polluted soil, frameshift alignments show that most alignable metagenomic reads contain frameshifts, suggesting that metagenomic analysis needs to use frameshift alignment to derive accurate results. C1 [Sheetlin, Sergey L.; Park, Yonil; Spouge, John L.] Natl Lib Med, Natl Ctr Biotechnol Informat, Bethesda, MD 20894 USA. [Frith, Martin C.] Natl Inst Adv Ind Sci & Technol, Computat Biol Res Ctr, Tokyo 1350064, Japan. RP Frith, MC (reprint author), Natl Inst Adv Ind Sci & Technol, Computat Biol Res Ctr, Tokyo 1350064, Japan. EM martin@cbrc.jp; spouge@ncbi.nlm.nih.gov OI Frith, Martin/0000-0003-0998-2859 FU Intramural Research Program of the NIH, National Library of Medicine FX This research was supported by the Intramural Research Program of the NIH, National Library of Medicine. NR 46 TC 3 Z9 3 U1 1 U2 9 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 1367-4803 EI 1460-2059 J9 BIOINFORMATICS JI Bioinformatics PD DEC 15 PY 2014 VL 30 IS 24 BP 3575 EP 3582 DI 10.1093/bioinformatics/btu576 PG 8 WC Biochemical Research Methods; Biotechnology & Applied Microbiology; Computer Science, Interdisciplinary Applications; Mathematical & Computational Biology; Statistics & Probability SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Computer Science; Mathematical & Computational Biology; Mathematics GA AW1LN UT WOS:000346051000019 PM 25172925 ER PT J AU Nizsaloczki, E Csomos, I Nagy, P Fazekas, Z Goldman, CK Waldmann, TA Damjanovich, S Vamosi, G Matyus, L Bodnar, A AF Nizsaloczki, Eniko Csomos, Istvan Nagy, Peter Fazekas, Zsolt Goldman, Carolyn K. Waldmann, Thomas A. Damjanovich, Sandor Vamosi, Gyoergy Matyus, Laszlo Bodnar, Andrea TI Distinct Spatial Relationship of the Interleukin-9 Receptor with Interleukin-2 Receptor and Major Histocompatibility Complex Glycoproteins in Human T Lymphoma Cells SO CHEMPHYSCHEM LA English DT Article DE confocal microscopy; FRET; membrane proteins; protein-protein interactions; receptors ID CLASS-I MOLECULES; RESONANCE ENERGY-TRANSFER; LIPID RAFTS; MEMBRANE RAFTS; SIGNAL-TRANSDUCTION; CYTOKINE RECEPTORS; FAMILY CYTOKINES; ALPHA-SUBUNITS; GAMMA-CHAIN; IL-2 AB The interleukin-9 receptor (IL-9R) consists of an a subunit and a gamma(c) chain that are shared with other cytokine receptors, including interleukin-2 receptor (IL-2R), an important regulator of T cells. We previously showed that IL-2R is expressed in common clusters with major histocompatibility complex (MHC) glycoproteins in lipid rafts of human T lymphoma cells, which raised the question about what the relationship between clusters of IL-2R/MHC and IL-9R is. Confocal microscopy colocalization and fluorescence resonance energy transfer experiments capable of detecting membrane protein organization at different size scales revealed nonrandom association of IL-9R with IL-2R/MHC clusters at the surface of human T lymphoma cells. Accommodation of IL-9R alpha in membrane areas segregated from the IL-2R/MHC domains was also detected. The bipartite nature of IL-9R distribution was mirrored by signal transducer and activator of transcription (STAT) activation results. Our data indicate that co-compartmentalization with MHC glycoproteins is a general property of gamma(c) receptors. Distribution of receptor chains between different membrane domains may regulate their function. C1 [Nizsaloczki, Eniko; Csomos, Istvan; Nagy, Peter; Fazekas, Zsolt; Damjanovich, Sandor; Vamosi, Gyoergy; Matyus, Laszlo; Bodnar, Andrea] Univ Debrecen, Dept Biophys & Cell Biol, Res Ctr Mol Med, H-4012 Debrecen, Hungary. [Goldman, Carolyn K.; Waldmann, Thomas A.] NCI, Metab Branch, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. RP Matyus, L (reprint author), Univ Debrecen, Dept Biophys & Cell Biol, Res Ctr Mol Med, POB 39, H-4012 Debrecen, Hungary. EM lmatyus@med.unideb.hu RI Nagy, Peter/D-2188-2013 OI Nagy, Peter/0000-0002-7466-805X FU New Hungary Development Plan; European Union; European Social Fund [TAMOP-4.2.1/B-09/1/KONV-2010-0007, 4.2.2/B-10/1-2010-0024, 4.2.2.A-11/1/KONV-2012-0023, 4.2.2-A-11/1/KONV-2012-0025, TAMOP-4.2.4.A/2-11/1-2012-0001]; National Excellence Program; State of Hungary; Hungarian Scientific Research Fund [CK 78179, K 103965, K 103906, NK 101337]; Baross Gabor Program [REG-EA-09-1-2009-0010]; Internal Research Program of the University of Debrecen [RH/885/2013]; National Cancer Institute, National Institutes of Health FX We thank Rita Szabo and Adrienn Bagosi for their excellent technical assistance. This work was supported by projects implemented through the New Hungary Development Plan and cofinanced by the European Union and the European Social Fund (grants TAMOP-4.2.1/B-09/1/KONV-2010-0007, 4.2.2/B-10/1-2010-0024, 4.2.2.A-11/1/KONV-2012-0023, and 4.2.2-A-11/1/KONV-2012-0025); the National Excellence Program co-financed by the European Union, the State of Hungary, and the European Social Fund (TAMOP-4.2.4.A/2-11/1-2012-0001); the Hungarian Scientific Research Fund (grants CK 78179, K 103965, K 103906, and NK 101337); and the Baross Gabor Program (REG-EA-09-1-2009-0010). The work was also supported by the Internal Research Program of the University of Debrecen (RH/885/2013) and the Intramural Research Program of the National Cancer Institute, National Institutes of Health. NR 50 TC 3 Z9 3 U1 0 U2 5 PU WILEY-V C H VERLAG GMBH PI WEINHEIM PA BOSCHSTRASSE 12, D-69469 WEINHEIM, GERMANY SN 1439-4235 EI 1439-7641 J9 CHEMPHYSCHEM JI ChemPhysChem PD DEC 15 PY 2014 VL 15 IS 18 BP 3969 EP 3978 DI 10.1002/cphc.201402501 PG 10 WC Chemistry, Physical; Physics, Atomic, Molecular & Chemical SC Chemistry; Physics GA AW1NQ UT WOS:000346056500010 PM 25297818 ER PT J AU Abd-Elmoniem, KZ Unsal, AB Eshera, S Matta, JR Muldoon, N McAreavey, D Purdy, JB Hazra, R Hadigan, C Gharib, AM AF Abd-Elmoniem, Khaled Z. Unsal, Aylin B. Eshera, Sarah Matta, Jatin R. Muldoon, Nancy McAreavey, Dorothea Purdy, Julia B. Hazra, Rohan Hadigan, Colleen Gharib, Ahmed M. TI Increased Coronary Vessel Wall Thickness in HIV-Infected Young Adults SO CLINICAL INFECTIOUS DISEASES LA English DT Article DE perinatal HIV; coronary artery; cardiovascular disease; antiretroviral therapy; smoking ID INTIMA-MEDIA THICKNESS; ANTIRETROVIRAL THERAPY; ARTERY-DISEASE; COMPUTED-TOMOGRAPHY; PROGNOSTIC VALUE; ATHEROSCLEROSIS; ANGIOGRAPHY; RISK; INFLAMMATION; VASCULATURE AB Background. Individuals with long-term human immunodeficiency virus (HIV) infection are at risk for premature vasculopathy and cardiovascular disease (CVD). We evaluated coronary vessel wall thickening, coronary plaque, and epicardial fat in patients infected with HIV early in life compared with healthy controls. Methods. This is a prospective cross-sectional study of 35 young adults who acquired HIV in early life and 11 healthy controls, free of CVD. Time resolved phase-sensitive dual inversion recovery black-blood vessel wall magnetic resonance imaging (TRAPD) was used to measure proximal right coronary artery (RCA) wall thickness, and multidetector computed tomography (CT) angiography was used to quantify coronary plaque and epicardial fat. Results. RCA vessel wall thickness was significantly increased in HIV-infected patients compared with sex-and race-matched controls (1.32 +/- 0.21 mm vs 1.09 +/- 0.14 mm, P = .002). No subject had discrete plaque on CT sufficient to cause luminal narrowing, and plaque was not related to RCA wall thickness. In multivariate regression analyses, smoking pack-years (P = .004) and HIV infection (P = .007) were independently associated with thicker RCA vessel walls. Epicardial fat did not differ between groups. Among the HIV-infected group, duration of antiretroviral therapy (ART) (P = .02), duration of stavudine exposure (P < .01), low-density lipoprotein cholesterol (P = .04), and smoking pack-years (P < .01) were positively correlated with RCA wall thickness. Conclusions. This investigation provides evidence of subclinical coronary vascular disease among individuals infected with HIV in early life. Increased duration of ART, hyperlipidemia, and smoking contributed to proximal RCA thickening, independent of atherosclerotic plaque quantified by CT. These modifiable risk factors appear to influence early atherogenesis as measured by coronary wall thickness and may be important targets for CVD risk reduction. C1 [Abd-Elmoniem, Khaled Z.; Eshera, Sarah; Matta, Jatin R.; Gharib, Ahmed M.] Natl Inst Diabet & Digest & Kidney Dis, Biomed & Metab Imaging Branch, Bethesda, MD USA. [Unsal, Aylin B.; Hadigan, Colleen] NIAID, Immunoregulat Lab, Bethesda, MD 20892 USA. [Muldoon, Nancy; McAreavey, Dorothea; Purdy, Julia B.] Ctr Clin, Crit Care Med Dept, Bethesda, MD USA. [Hazra, Rohan] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Maternal & Pediat Infect Dis Branch, NIH, Bethesda, MD USA. RP Hadigan, C (reprint author), NIAID, Immunoregulat Lab, NIH, 10 Ctr Dr,11C103, Bethesda, MD 20892 USA. EM hadiganc@niaid.nih.gov RI Gharib, Ahmed/O-2629-2016; Abd-Elmoniem, Khaled/B-9289-2008 OI Gharib, Ahmed/0000-0002-2476-481X; Abd-Elmoniem, Khaled/0000-0002-1001-1702 FU National Institutes of Health through the National Institute of Allergy and Infectious Diseases; National Institutes of Health through the National Institute of Diabetes and Digestive and Kidney Diseases; National Institutes of Health through the National Institutes of Health Clinical Center FX This work was supported by the National Institutes of Health through the National Institute of Allergy and Infectious Diseases Intramural Research Program, the National Institute of Diabetes and Digestive and Kidney Diseases Intramural Research Program, and the National Institutes of Health Clinical Center. NR 35 TC 5 Z9 5 U1 0 U2 1 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 1058-4838 EI 1537-6591 J9 CLIN INFECT DIS JI Clin. Infect. Dis. PD DEC 15 PY 2014 VL 59 IS 12 BP 1779 EP 1786 DI 10.1093/cid/ciu672 PG 8 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA AU9KM UT WOS:000345911500025 PM 25159580 ER PT J AU Smrz, D Cruse, G Beaven, MA Kirshenbaum, A Metcalfe, DD Gilfillan, AM AF Smrz, Daniel Cruse, Glenn Beaven, Michael A. Kirshenbaum, Arnold Metcalfe, Dean D. Gilfillan, Alasdair M. TI Rictor Negatively Regulates High-Affinity Receptors for IgE-Induced Mast Cell Degranulation SO JOURNAL OF IMMUNOLOGY LA English DT Article ID FC-EPSILON-RI; P70 S6 KINASE; MAMMALIAN TARGET; MTOR COMPLEX; ENDOPLASMIC-RETICULUM; AKT PHOSPHORYLATION; ACTIN CYTOSKELETON; 3T3-L1 ADIPOCYTES; MEDIATOR RELEASE; RAPAMYCIN AB Rictor is a regulatory component of the mammalian target of rapamycin (mTOR) complex 2 (mTORC2). We have previously demonstrated that rictor expression is substantially downregulated in terminally differentiated mast cells as compared with their immature or transformed counterparts. However, it is not known whether rictor and mTORC2 regulate mast cell activation. In this article, we show that mast cell degranulation induced by aggregation of high-affinity receptors for IgE (Fc epsilon pn RI) is negatively regulated by rictor independently of mTOR. We found that inhibition of mTORC2 by the dual mTORC1/mTORC2 inhibitor Torin1 or by downregulation of mTOR by short hairpin RNA had no impact on Fc epsilon RI-induced degranulation, whereas downregulation of rictor itself resulted in an increased sensitivity (similar to 50-fold) of cells to Fc epsilon RI aggregation with enhancement of degranulation. This was linked to a similar enhancement in calcium mobilization and cytoskeletal rearrangement attributable to increased phosphorylation of LAT and PLC gamma(1). In contrast, degranulation and calcium responses elicited by the G protein-coupled receptor ligand, C3a, or by thapsigargin, which induces a receptor-independent calcium signal, was unaffected by rictor knockdown. Overexpression of rictor, in contrast with knockdown, suppressed Fc epsilon RI-mediated degranulation. Taken together, these data provide evidence that rictor is a multifunctional signaling regulator that can regulate Fc epsilon RI-mediated degranulation independently of mTORC2. C1 [Smrz, Daniel; Cruse, Glenn; Kirshenbaum, Arnold; Metcalfe, Dean D.; Gilfillan, Alasdair M.] NIAID, Lab Allerg Dis, NIH, Bethesda, MD 20892 USA. [Beaven, Michael A.] NHLBI, Lab Mol Immunol, NIH, Bethesda, MD 20892 USA. RP Smrz, D (reprint author), Charles Univ Prague, Sch Med 2, Inst Immunol, V Uvalu 84, Prague 15006 5, Czech Republic. EM daniel.smrz@lfmotol.cuni.cz RI Smrz, Daniel/D-4853-2014 OI Smrz, Daniel/0000-0003-0143-8744 FU Division of Intramural Research programs within the National Institute of Allergy and Infectious Diseases; National Heart, Lung, and Blood Institute FX This work was supported by Division of Intramural Research programs within the National Institute of Allergy and Infectious Diseases (to D.S., G.C., A.K., D.D.M., and A.M.G.) and the National Heart, Lung, and Blood Institute (to M.A.B.). NR 69 TC 1 Z9 1 U1 1 U2 5 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 EI 1550-6606 J9 J IMMUNOL JI J. Immunol. PD DEC 15 PY 2014 VL 193 IS 12 BP 5924 EP 5932 DI 10.4049/jimmunol.1303495 PG 9 WC Immunology SC Immunology GA AW1XQ UT WOS:000346082400021 PM 25378594 ER PT J AU Stevens, LA Barbieri, JT Piszczek, G Otuonye, AN Levine, RL Zheng, G Moss, J AF Stevens, Linda A. Barbieri, Joseph T. Piszczek, Grzegorz Otuonye, Amy N. Levine, Rodney L. Zheng, Gang Moss, Joel TI Nonenzymatic Conversion of ADP-Ribosylated Arginines to Ornithine Alters the Biological Activities of Human Neutrophil Peptide-1 SO JOURNAL OF IMMUNOLOGY LA English DT Article ID IDIOPATHIC PULMONARY-FIBROSIS; BRONCHIAL EPITHELIAL-CELLS; HUMAN LUNG FIBROBLASTS; ALPHA-DEFENSINS; ANTIMICROBIAL PEPTIDES; ALPHA(1)-ANTITRYPSIN DEFICIENCY; INTERLEUKIN-8 PRODUCTION; SIGNALING PATHWAY; IN-VITRO; EXPRESSION AB Activated neutrophils, recruited to the airway of diseased lung, release human neutrophil peptides (HNP1-4) that are cytotoxic to airway cells as well as microbes. Airway epithelial cells express arginine-specific ADP ribosyltransferase (ART)-1, a GPI-anchored ART that transfers ADP-ribose from NAD to arginines 14 and 24 of HNP-1. We previously reported that ADP-ribosyl-arginine is converted nonenzymatically to ornithine and that ADP-ribosylated HNP-1 and ADP-ribosyl-HNP-(ornithine) were isolated from bronchoalveolar lavage fluid of a patient with idiopathic pulmonary fibrosis, indicating that these reactions occur in vivo. To determine effects of HNP-ornithine on the airway, three analogs of HNP-1, HNP-(R14orn), HNP-(R24orn), and HNP-(R14,24orn), were tested for their activity against Pseudomonas aeruginosa, Escherichia coli, and Staphylococcus aureus; their cytotoxic effects on A549, NCI-H441, small airway epithelial-like cells, and normal human lung fibroblasts; and their ability to stimulate IL-8 and TGF-beta 1 release from A549 cells, and to serve as ART1 substrates. HNP and the three analogs had similar effects on IL-8 and TGF-beta 1 release from A549 cells and were all cytotoxic for small airway epithelial cells, NCI-H441, and normal human lung fibroblasts. HNP-(R14,24orn), when compared with HNP-1 and HNP-1 with a single ornithine substitution for arginine 14 or 24, exhibited reduced cytotoxicity, but it enhanced proliferation of A549 cells and had antibacterial activity. Thus, arginines 14 and 24, which can be ADP ribosylated by ART1, are critical to the regulation of the cytotoxic and antibacterial effects of HNP-1. The HNP analog, HNP-(R14,24orn), lacks the epithelial cell cytotoxicity of HNP-1, but partially retains its antibacterial activity and thus may have clinical applications in airway disease. C1 [Stevens, Linda A.; Otuonye, Amy N.; Moss, Joel] NHLBI, Cardiovasc & Pulm Branch, NIH, Bethesda, MD 20892 USA. [Barbieri, Joseph T.] Med Coll Wisconsin, Milwaukee, WI 53226 USA. [Piszczek, Grzegorz] NHLBI, Biophys Core Facil, NIH, Bethesda, MD 20892 USA. [Levine, Rodney L.] NHLBI, Biochem Lab, NIH, Bethesda, MD 20892 USA. [Zheng, Gang] NHLBI, Off Biostat Res, NIH, Bethesda, MD 20892 USA. RP Moss, J (reprint author), NIH, Room 6D05,Bldg 10,9000 Rockville Pike, Bethesda, MD 20892 USA. EM mossj@nhlbi.nih.gov RI Levine, Rodney/D-9885-2011 FU Intramural Research Program of the National Institutes of Health, National Heart, Lung, and Blood Institute FX This work was supported by the Intramural Research Program of the National Institutes of Health, National Heart, Lung, and Blood Institute. NR 49 TC 0 Z9 0 U1 0 U2 6 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 EI 1550-6606 J9 J IMMUNOL JI J. Immunol. PD DEC 15 PY 2014 VL 193 IS 12 BP 6144 EP 6151 DI 10.4049/jimmunol.1303068 PG 8 WC Immunology SC Immunology GA AW1XQ UT WOS:000346082400041 PM 25392530 ER PT J AU Gordon, SN Doster, MN Kines, RC Keele, BF Brocca-Cofano, E Guan, YJ Pegu, P Liyanage, NPM Vaccari, M Cuburu, N Buck, CB Ferrari, G Montefiori, D Piatak, M Lifson, JD Xenophontos, AM Venzon, D Robert-Guroff, M Graham, BS Lowy, DR Schiller, JT Franchini, G AF Gordon, Shari N. Doster, Melvin N. Kines, Rhonda C. Keele, Brandon F. Brocca-Cofano, Egidio Guan, Yongjun Pegu, Poonam Liyanage, Namal P. M. Vaccari, Monica Cuburu, Nicolas Buck, Christopher B. Ferrari, Guido Montefiori, David Piatak, Michael, Jr. Lifson, Jeffrey D. Xenophontos, Anastasia M. Venzon, David Robert-Guroff, Marjorie Graham, Barney S. Lowy, Douglas R. Schiller, John T. Franchini, Genoveffa TI Antibody to the gp120 V1/V2 Loops and CD4(+) and CD8(+) T Cell Responses in Protection from SIVmac251 Vaginal Acquisition and Persistent Viremia SO JOURNAL OF IMMUNOLOGY LA English DT Article ID SIMIAN IMMUNODEFICIENCY VIRUS; PREVENT HIV-1 INFECTION; HIGHLY PATHOGENIC SIV; RHESUS MACAQUES; EFFICACY TRIAL; DOUBLE-BLIND; INTRAVAGINAL IMMUNIZATION; GAG/POL/NEF VACCINE; MUCOSAL INFECTION; ENVELOPE PROTEIN AB The human papillomavirus pseudovirions (HPV-PsVs) approach is an effective gene-delivery system that can prime or boost an immune response in the vaginal tract of nonhuman primates and mice. Intravaginal vaccination with HPV-PsVs expressing SIV genes, combined with an i.m. gp120 protein injection, induced humoral and cellular SIV-specific responses in macaques. Priming systemic immune responses with i.m. immunization with ALVAC-SIV vaccines, followed by intravaginal HPV-PsV-SIV/gp120 boosting, expanded and/or recruited T cells in the female genital tract. Using a stringent repeated low-dose intravaginal challenge with the highly pathogenic SIVmac251, we show that although these regimens did not demonstrate significant protection from virus acquisition, they provided control of viremia in a number of animals. High-avidity Ab responses to the envelope gp120 V1/V2 region correlated with delayed SIVmac251 acquisition, whereas virus levels in mucosal tissues were inversely correlated with antienvelope CD4(+) T cell responses. CD8(+) T cell depletion in animals with controlled viremia caused an increase in tissue virus load in some animals, suggesting a role for CD8(+) T cells in virus control. This study highlights the importance of CD8(+) cells and antienvelope CD4(+) T cells in curtailing virus replication and antienvelope V1/V2 Abs in preventing SIVmac251 acquisition. C1 [Gordon, Shari N.; Doster, Melvin N.; Pegu, Poonam; Liyanage, Namal P. M.; Vaccari, Monica; Xenophontos, Anastasia M.; Franchini, Genoveffa] NCI, Anim Models & Retroviral Vaccines Sect, Bethesda, MD 20892 USA. [Kines, Rhonda C.; Cuburu, Nicolas; Buck, Christopher B.; Lowy, Douglas R.; Schiller, John T.] NCI, Ctr Canc Res, Cellular Oncol Lab, Bethesda, MD 20892 USA. [Guan, Yongjun] Univ Maryland, Sch Med, Inst Human Virol, Div Basic Sci & Vaccine Res, Baltimore, MD 21201 USA. [Ferrari, Guido; Montefiori, David] Duke Univ, Med Ctr, Dept Surg, Durham, NC 27710 USA. [Venzon, David] NCI, Biostat & Data Management Sect, Bethesda, MD 20892 USA. [Graham, Barney S.] NIAID, Vaccine Res Ctr, Bethesda, MD 20892 USA. RP Franchini, G (reprint author), NCI, Anim Models & Retroviral Vaccines Sect, 9000 Rockville Pike,Bldg 41,Room D804, Bethesda, MD 20892 USA. EM franchig@mail.nih.gov RI Ferrari, Guido/A-6088-2015; OI Buck, Christopher/0000-0003-3165-8094 FU Office of AIDS award; National Cancer Institute [HHSN261200800001E, HHSN266200400088C] FX This work was supported by the intramural budget (to G.F. and J.T.S.), by an Office of AIDS award, and in part by federal funds from the National Cancer Institute under Contracts HHSN261200800001E and HHSN266200400088C. NR 55 TC 7 Z9 7 U1 0 U2 4 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 EI 1550-6606 J9 J IMMUNOL JI J. Immunol. PD DEC 15 PY 2014 VL 193 IS 12 BP 6172 EP 6183 DI 10.4049/jimmunol.1401504 PG 12 WC Immunology SC Immunology GA AW1XQ UT WOS:000346082400044 PM 25398324 ER PT J AU Beigi, RH Fortner, KB Munoz, FM Roberts, J Gordon, JL Han, HH Glenn, G Dormitzer, PR Gu, XX Read, JS Edwards, K Patel, SM Swamy, GK AF Beigi, Richard H. Fortner, Kimberly B. Munoz, Flor M. Roberts, Jeff Gordon, Jennifer L. Han, Htay Htay Glenn, Greg Dormitzer, Philip R. Gu, Xing Xing Read, Jennifer S. Edwards, Kathryn Patel, Shital M. Swamy, Geeta K. TI Maternal Immunization: Opportunities for Scientific Advancement SO CLINICAL INFECTIOUS DISEASES LA English DT Article DE maternal; immunization; vaccines; pregnancy; research ID PREGNANT-WOMEN; INFLUENZA IMMUNIZATION; DEVELOPING-COUNTRIES; TETANUS-DIPHTHERIA; ANTIBODY-RESPONSE; IMMUNE-RESPONSE; BREAST-MILK; VACCINE; INFANTS; MOTHERS AB Maternal immunization is an effective strategy to prevent and/or minimize the severity of infectious diseases in pregnant women and their infants. Based on the success of vaccination programs to prevent maternal and neonatal tetanus, maternal immunization has been well received in the United States and globally as a promising strategy for the prevention of other vaccine-preventable diseases that threaten pregnant women and infants, such as influenza and pertussis. Given the promise for reducing the burden of infectious conditions of perinatal significance through the development of vaccines against relevant pathogens, the Division of Microbiology and Infectious Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health (NIH) sponsored a series of meetings to foster progress toward clinical development of vaccines for use in pregnancy. A multidisciplinary group of stakeholders convened at the NIH in December 2013 to identify potential barriers and opportunities for scientific advancement in maternal immunization. C1 [Beigi, Richard H.] Univ Pittsburgh, Med Ctr, Magee Womens Hosp, Dept Obstet Gynecol & Reprod Sci, Pittsburgh, PA 15260 USA. [Fortner, Kimberly B.] Vanderbilt Univ, Dept Obstet & Gynecol, Nashville, TN 37235 USA. [Munoz, Flor M.] Baylor Coll Med, Dept Pediat, Houston, TX 77030 USA. [Munoz, Flor M.; Patel, Shital M.] Baylor Coll Med, Dept Mol Virol & Microbiol, Houston, TX 77030 USA. [Roberts, Jeff] US FDA, Ctr Biol Evaluat & Res, Off Vaccines Res & Review, Silver Spring, MD USA. [Gordon, Jennifer L.] US Dept HHS, Natl Vaccine Program Off, Off Assistant Secretary Hlth, Washington, DC 20201 USA. [Han, Htay Htay] GlaxoSmithKline Vaccines, King Of Prussia, PA USA. [Glenn, Greg] Novavax Inc, Gaithersburg, MD USA. [Dormitzer, Philip R.] Novartis Vaccines & Diagnost Inc, Cambridge, MA USA. [Gu, Xing Xing; Read, Jennifer S.] NIAID, NIH, Bethesda, MD 20892 USA. [Edwards, Kathryn] Vanderbilt Univ, Dept Pediat, Vanderbilt Vaccine Res Program, Nashville, TN USA. [Patel, Shital M.] Baylor Coll Med, Dept Med, Houston, TX 77030 USA. [Swamy, Geeta K.] Duke Univ, Dept Obstet & Gynecol, Durham, NC USA. RP Beigi, RH (reprint author), UPMC, Magee Womens Hosp, Dept Ob Gyn RS, 300 Halket St, Pittsburgh, PA 15213 USA. EM rbeigi@magee.edu FU Bill & Melinda Gates Foundation FX This article appears as part of the supplement "Including Pregnant Women in Clinical Trials of Antimicrobials and Vaccines," sponsored by the Bill & Melinda Gates Foundation. NR 53 TC 7 Z9 7 U1 1 U2 14 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 1058-4838 EI 1537-6591 J9 CLIN INFECT DIS JI Clin. Infect. Dis. PD DEC 15 PY 2014 VL 59 SU 7 BP S408 EP S414 DI 10.1093/cid/ciu708 PG 7 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA AU9LB UT WOS:000345913100003 PM 25425719 ER PT J AU Frew, PM Saint-Victor, DS Isaacs, MB Kim, S Swamy, GK Sheffield, JS Edwards, KM Villafana, T Kamagate, O Ault, K AF Frew, Paula M. Saint-Victor, Diane S. Isaacs, Margaret Brewinski Kim, Sonnie Swamy, Geeta K. Sheffield, Jeanne S. Edwards, Kathryn M. Villafana, Tonya Kamagate, Ouda Ault, Kevin TI Recruitment and Retention of Pregnant Women Into Clinical Research Trials: An Overview of Challenges, Facilitators, and Best Practices SO CLINICAL INFECTIOUS DISEASES LA English DT Article DE pregnant women; clinical research trials; recruitment; retention; vulnerable populations ID RANDOMIZED-CONTROLLED-TRIAL; HEALTH PROMOTION PROGRAMS; HIV VACCINE RESEARCH; INFLUENZA VACCINATION; LOW-INCOME; AFRICAN-AMERICANS; POSTPARTUM WOMEN; PARTICIPATION; MODEL; IMMUNIZATION AB Pregnant women are a vulnerable group who are needed in clinical research studies to advance prevention and treatment options for this population. Yet, pregnant women remain underrepresented in clinical research. Through the lens of the socioecological model, we highlight reported barriers and facilitators to recruitment and retention of pregnant women in studies that sought their participation. We trace historical, policy-based reasons for the exclusion of pregnant women in clinical studies to present-day rationale for inclusion of this group. The findings highlight why it has been difficult to recruit and retain this population over time. A body of literature suggests that integrative sampling and recruitment methods that leverage the influence and reach of prenatal providers will overcome recruitment challenges. We argue that these strategies, in combination with building strong engagement with existing community-based organizations, will enable teams to more effectively promote and retain pregnant women in future longitudinal cohort studies. C1 [Frew, Paula M.; Saint-Victor, Diane S.; Kamagate, Ouda] Emory Univ, Sch Med, Dept Med, Div Infect Dis, Atlanta, GA USA. [Frew, Paula M.] Emory Univ, Dept Behav Sci & Hlth Educ, Emory Rollins Sch Publ Hlth, Atlanta, GA 30322 USA. [Isaacs, Margaret Brewinski] NIH, Off Res Womens Hlth, Bethesda, MD 20892 USA. [Kim, Sonnie] NIAID, NIH, Bethesda, MD 20892 USA. [Swamy, Geeta K.] Duke Univ, Durham, NC USA. [Sheffield, Jeanne S.] Univ Texas SW Med Ctr Dallas, Dallas, TX 75390 USA. [Edwards, Kathryn M.] Vanderbilt Univ, Med Ctr, Nashville, TN USA. [Villafana, Tonya] MedImmune, Gaithersburg, MD USA. [Ault, Kevin] Univ Kansas, Med Ctr, Dept Obstet & Gynecol, Kansas City, KS USA. RP Frew, PM (reprint author), Emory Univ, Sch Med, Dept Med, Div Infect Dis, 500 Irvin Court,Ste 200, Decatur, GA 30030 USA. EM pfrew@emory.edu FU Bill & Melinda Gates Foundation; Division of Microbiology and Infectious Diseases of the National Institute of Allergy and Infectious Diseases, National Institutes of Health FX This article was supported by an unrestricted grant from the Bill & Melinda Gates Foundation and the Division of Microbiology and Infectious Diseases of the National Institute of Allergy and Infectious Diseases, National Institutes of Health. NR 85 TC 8 Z9 8 U1 1 U2 13 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 1058-4838 EI 1537-6591 J9 CLIN INFECT DIS JI Clin. Infect. Dis. PD DEC 15 PY 2014 VL 59 SU 7 BP S400 EP S407 DI 10.1093/cid/ciu726 PG 8 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA AU9LB UT WOS:000345913100002 PM 25425718 ER PT J AU Munoz, FM Weisman, LE Read, JS Siberry, G Kotloff, K Friedman, J Higgins, RD Hill, H Seifert, H Nesin, M AF Munoz, Flor M. Weisman, Leonard E. Read, Jennifer S. Siberry, George Kotloff, Karen Friedman, Jennifer Higgins, Rosemary D. Hill, Heather Seifert, Harry Nesin, Mirjana TI Assessment of Safety in Newborns of Mothers Participating in Clinical Trials of Vaccines Administered During Pregnancy SO CLINICAL INFECTIOUS DISEASES LA English DT Article DE maternal immunization; safety; pregnancy; vaccines; clinical trials ID MONOCLONAL-ANTIBODY; IMMUNIZATION; INFANTS; WOMEN; TDAP; IMMUNOGENICITY; PAGIBAXIMAB; PREVENTION; DIPHTHERIA AB A panel of experts convened by the Division of Microbiology and Infectious Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, developed proposed guidelines for the evaluation of adverse events in newborns of women participating in clinical trials of maternal immunization in the United States. C1 [Munoz, Flor M.; Weisman, Leonard E.] Baylor Coll Med, Dept Pediat, Houston, TX 77030 USA. [Munoz, Flor M.] Baylor Coll Med, Dept Mol Virol & Microbiol, Houston, TX 77030 USA. [Read, Jennifer S.] NIAID, Div Allergy Immunol & Transplantat, Bethesda, MD 20892 USA. [Siberry, George] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Maternal & Pediat Infect Dis Branch, NIH, Bethesda, MD USA. [Kotloff, Karen] Univ Maryland, Dept Pediat, Baltimore, MD 21201 USA. [Friedman, Jennifer] Brown Univ, Rhode Isl Hosp, Ctr Int Hlth Res, Providence, RI 02903 USA. [Friedman, Jennifer] Brown Univ, Dept Pediat, Alpert Med Sch, Providence, RI 02912 USA. [Higgins, Rosemary D.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Pregnancy & Perinatol Branch, NIH, Bethesda, MD USA. [Hill, Heather] EMMES Corp, Rockville, MD USA. [Seifert, Harry] GlaxoSmithKline Vaccines, King Of Prussia, PA USA. [Nesin, Mirjana] NIAID, Div Microbiol & Infect Dis, NIH, Bethesda, MD 20892 USA. RP Munoz, FM (reprint author), Baylor Coll Med, Dept Pediat Mol Virol & Microbiol, One Baylor Plaza,BCM 280, Houston, TX 77030 USA. EM florm@bcm.edu FU Bill & Melinda Gates Foundation FX This article appears as part of the supplement "Including Pregnant Women in Clinical Trials of Antimicrobials and Vaccines," sponsored by the Bill & Melinda Gates Foundation. NR 40 TC 7 Z9 7 U1 1 U2 8 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 1058-4838 EI 1537-6591 J9 CLIN INFECT DIS JI Clin. Infect. Dis. PD DEC 15 PY 2014 VL 59 SU 7 BP S415 EP S427 DI 10.1093/cid/ciu727 PG 13 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA AU9LB UT WOS:000345913100004 PM 25425720 ER PT J AU Rasmussen, SA Hernandez-Diaz, S Abdul-Rahman, OA Sahin, L Petrie, CR Keppler-Noreuil, KM Frey, SE Mason, RM Nesin, M Carey, JC AF Rasmussen, Sonja A. Hernandez-Diaz, Sonia Abdul-Rahman, Omar A. Sahin, Leyla Petrie, Carey R. Keppler-Noreuil, Kim M. Frey, Sharon E. Mason, Robin M. Nesin, Mirjana Carey, John C. TI Assessment of Congenital Anomalies in Infants Born to Pregnant Women Enrolled in Clinical Trials SO CLINICAL INFECTIOUS DISEASES LA English DT Article DE congenital anomalies; birth defects; clinical trials; pregnant women ID MORPHOLOGY STANDARD TERMINOLOGY; FETAL ALCOHOL SYNDROME; BIRTH-DEFECTS; POSTMARKETING SURVEILLANCE; MAJOR MALFORMATIONS; EXCLUSION CRITERIA; TERATOGEN UPDATE; PREDICTIVE VALUE; NEWBORN-INFANTS; MINOR ANOMALIES AB In 2011 and 2012, the Division of Microbiology and Infectious Diseases at the National Institute of Allergy and Infectious Diseases, National Institutes of Health, held a series of meetings to provide guidance to investigators regarding study design of clinical trials of vaccines and antimicrobial medications that enroll pregnant women. Assessment of congenital anomalies among infants born to women enrolled in these trials was recognized as a challenging issue, and a workgroup with expertise in epidemiology, pediatrics, genetics, dysmorphology, clinical trials, and infectious diseases was formed to address this issue. The workgroup considered 3 approaches for congenital anomalies assessment that have been developed for use in other studies: (1) maternal report combined with medical records review, (2) standardized photographic assessment and physical examination by a health professional who has received specific training in congenital anomalies, and (3) standardized physical examination by a trained dysmorphologist (combined with maternal interview and medical records review). The strengths and limitations of these approaches were discussed with regard to their use in clinical trials. None of the approaches was deemed appropriate for use in all clinical trials. Instead, the workgroup acknowledged that decisions regarding the optimal method of assessment of congenital anomalies will likely vary depending on the clinical trial, its setting, and the agent under study; in some cases, a combination of approaches may be appropriate. The workgroup recognized the need for more research on approaches to the assessment of congenital anomalies to better guide investigators in optimal design of clinical trials that enroll pregnant women. C1 [Rasmussen, Sonja A.] Ctr Dis Control & Prevent, Atlanta, GA USA. [Hernandez-Diaz, Sonia] Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA. [Abdul-Rahman, Omar A.] Univ Mississippi, Med Ctr, University, MS 38677 USA. [Sahin, Leyla] US FDA, Silver Spring, MD USA. [Petrie, Carey R.] EMMES Corp, Rockville, MD USA. [Keppler-Noreuil, Kim M.; Mason, Robin M.; Nesin, Mirjana] NIH, Bethesda, MD 20892 USA. [Frey, Sharon E.] St Louis Univ, Sch Med, St Louis, MO 63103 USA. [Carey, John C.] Univ Utah, Sch Med, Salt Lake City, UT USA. RP Rasmussen, SA (reprint author), CDC, 1600 Clifton Rd,MS A-28, Atlanta, GA 30333 USA. EM skr9@cdc.gov FU NIAID (HHS) [HHSN272200800013C] FX C. R. P.'s work on the article was supported by NIAID contract (HHS contract HHSN272200800013C). NR 40 TC 1 Z9 1 U1 1 U2 12 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 1058-4838 EI 1537-6591 J9 CLIN INFECT DIS JI Clin. Infect. Dis. PD DEC 15 PY 2014 VL 59 SU 7 BP S428 EP S436 DI 10.1093/cid/ciu738 PG 9 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA AU9LB UT WOS:000345913100005 PM 25425721 ER PT J AU Sheffield, JS Siegel, D Mirochnick, M Heine, RP Nguyen, C Bergman, KL Savic, RM Long, J Dooley, KE Nesin, M AF Sheffield, Jeanne S. Siegel, David Mirochnick, Mark Heine, R. Phillips Nguyen, Christine Bergman, Kimberly L. Savic, Rada M. Long, Jill Dooley, Kelly E. Nesin, Mirjana TI Designing Drug Trials: Considerations for Pregnant Women SO CLINICAL INFECTIOUS DISEASES LA English DT Article DE pregnancy; drug trials; pharmacokinetics ID MEDICATIONS AB Clinical pharmacology studies that describe the pharmacokinetics and pharmacodynamics of drugs in pregnant women are critical for informing on the safe and effective use of drugs during pregnancy. That being said, multiple factors have hindered the ability to study drugs in pregnant patients. These include concerns for maternal and fetal safety, ethical considerations, the difficulty in designing appropriate trials to assess the study objectives, and funding limitations. This document summarizes the recommendations of a panel of experts convened by the Division of Microbiology and Infectious Diseases at the National Institute of Allergy and Infectious Diseases, National Institutes of Health. These experts were charged with reviewing the issues related to the development of preclinical and clinical drug studies in pregnant women and to develop strategies for addressing these issues. These findings may also be utilized in the development of future drug studies involving pregnant women and their fetus/neonate. C1 [Sheffield, Jeanne S.] Univ Texas SW Med Ctr Dallas, Div Maternal Fetal Med, Dallas, TX 75390 USA. [Siegel, David] NICHHD, NIH, Bethesda, MD 20892 USA. [Mirochnick, Mark] Boston Univ, Div Neonatol, Boston, MA 02215 USA. [Heine, R. Phillips] Duke Univ, Div Maternal Fetal Med, Durham, NC USA. [Nguyen, Christine] Ctr Drug Evaluat & Res, Div Bone Reprod & Urol Prod, Off Drug Evaluat 3, Silver Spring, MD USA. [Bergman, Kimberly L.] US FDA, Off Clin Pharmacol, Off Translat Sci, Silver Spring, MD USA. [Savic, Rada M.] Univ Calif San Francisco, Dept Bioengn, San Francisco, CA 94143 USA. [Long, Jill; Nesin, Mirjana] NIAID, Div Microbiol & Infect Dis, NIH, Bethesda, MD 20892 USA. [Dooley, Kelly E.] Johns Hopkins Univ, Sch Med, Div Infect Dis, Baltimore, MD 21205 USA. RP Sheffield, JS (reprint author), 5323 Harry Hines Blvd, Dallas, TX 75390 USA. EM jeanne.sheffield@utsouthwestern.edu FU Bill & Melinda Gates Foundation; Division of Microbiology and Infectious Diseases of the National Institute of Allergy and Infectious Diseases, National Institutes of Health FX This article was supported by an unrestricted grant from the Bill & Melinda Gates Foundation and the Division of Microbiology and Infectious Diseases of the National Institute of Allergy and Infectious Diseases, National Institutes of Health. NR 17 TC 6 Z9 6 U1 0 U2 8 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 1058-4838 EI 1537-6591 J9 CLIN INFECT DIS JI Clin. Infect. Dis. PD DEC 15 PY 2014 VL 59 SU 7 BP S437 EP S444 DI 10.1093/cid/ciu709 PG 8 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA AU9LB UT WOS:000345913100006 PM 25425722 ER PT J AU Sakiani, S Koh, C Heller, T AF Sakiani, Sasan Koh, Christopher Heller, Theo TI Understanding the Presence of False-Positive Antibodies in Acute Hepatitis SO JOURNAL OF INFECTIOUS DISEASES LA English DT Article DE acute hepatitis; liver; hepatitis C virus; antibodies; false-positive antibodies ID C VIRUS-INFECTION; AUTOIMMUNITY; TESTS; LIVER; PREVALENCE; SYPHILIS AB Although false-positive antibodies (FPAs) have been well described in chronic hepatitis C virus (HCV), this has not been evaluated in acute viral hepatitis. Patients with acute viral hepatitis underwent antibody testing for other causes of liver disease and sexually transmitted diseases. Those with antibody positivity underwent confirmatory testing and monitoring. Patients with FPAs were compared with patients with acute hepatitis C infection without FPAs. In total 7 of 24 patients (29%) had FPAs. FPAs during acute viral hepatitis are associated with higher IgM levels and higher ESR in acute HCV. This has both mechanistic and clinical implications and should be evaluated further. C1 [Sakiani, Sasan; Koh, Christopher; Heller, Theo] NIDDK, Translat Hepatol Unit, Liver Dis Branch, NIH, Bethesda, MD 20892 USA. [Sakiani, Sasan] Case Western Univ, Metrohlth Med Ctr, Div Gastroenterol & Hepatol, Cleveland, OH USA. RP Sakiani, S (reprint author), NIDDK, Translat Hepatol Unit, Liver Dis Branch, NIH, Bldg 10,Rm 9B16,10 Ctr Dr,MSC 1800, Bethesda, MD 20892 USA. EM christopher.koh@nih.gov FU Intramural Research Program of the NIDDK, NIH FX This research was supported by the Intramural Research Program of the NIDDK, NIH. NR 15 TC 3 Z9 3 U1 0 U2 4 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0022-1899 EI 1537-6613 J9 J INFECT DIS JI J. Infect. Dis. PD DEC 15 PY 2014 VL 210 IS 12 BP 1886 EP 1889 DI 10.1093/infdis/jiu348 PG 4 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA AU7HK UT WOS:000345771200006 PM 24943727 ER PT J AU Kuhs, KAL Gonzalez, P Rodriguez, AC van Doorn, LJ Schiffman, M Struijk, L Chen, S Quint, W Lowy, DR Porras, C DelVecchio, C Jimenez, S Safaeian, M Schiller, JT Wacholder, S Herrero, R Hildesheim, A Kreimer, AR AF Kuhs, Krystle A. Lang Gonzalez, Paula Cecilia Rodriguez, Ana van Doorn, Leen-Jan Schiffman, Mark Struijk, Linda Chen, Sabrina Quint, Wim Lowy, Douglas R. Porras, Carolina DelVecchio, Corey Jimenez, Silvia Safaeian, Mahboobeh Schiller, John T. Wacholder, Sholom Herrero, Rolando Hildesheim, Allan Kreimer, Aimee R. CA Costa Rica Vaccine Trial Grp TI Reduced Prevalence of Vulvar HPV16/18 Infection Among Women Who Received the HPV16/18 Bivalent Vaccine: A Nested Analysis Within the Costa Rica Vaccine Trial SO JOURNAL OF INFECTIOUS DISEASES LA English DT Article DE Costa Rica; HPV; HPV vaccine; vulvar human papillomavirus vaccine ID HUMAN-PAPILLOMAVIRUS INFECTIONS; YOUNG-WOMEN; INTRAEPITHELIAL NEOPLASIA; BROAD-SPECTRUM; TRENDS; CANCER; PCR; CARCINOMA; EFFICACY; DISEASES AB Vaccine efficacy (VE) against vulvar human papillomavirus (HPV) infection has not been reported and data regarding its epidemiology are sparse. Women (n = 5404) age 22-29 present at the 4-year study visit of the Costa Rica Vaccine Trial provided vulvar and cervical samples. A subset (n = 1044) was tested for HPV DNA (SPF10/LiPA(25) version 1). VE against 1-time detection of vulvar HPV16/18 among HPV vaccinated versus unvaccinated women was calculated and compared to the cervix. Prevalence of and risk factors for HPV were evaluated in the control arm (n = 536). Vulvar HPV16/18 VE (54.1%; 95% confidence interval [CI], 4.9%-79.1%) was comparable to cervix (45.8%; 95% CI, 6.4%-69.4%). Vulvar and cervical HPV16 prevalence within the control arm was 3.0% and 4.7%, respectively. Independent risk factors for vulvar HPV were similar to cervix and included: age (adjusted odds ratio [aOR] 0.5 [95% CI, .3-.9] a parts per thousand yen28 vs 22-23]); marital status (aOR 2.3 [95% CI, 1.5-3.5] single vs married/living-as-married); and number of sexual partners (aOR 3.6 [95% CI, 1.9-7.0] a parts per thousand yen6 vs 1). In this intention-to-treat analysis, VE against vulvar and cervical HPV16/18 were comparable 4 years following vaccination. Risk factors for HPV were similar by anatomic site. NCT00128661. C1 [Kuhs, Krystle A. Lang; Schiffman, Mark; Lowy, Douglas R.; Safaeian, Mahboobeh; Schiller, John T.; Wacholder, Sholom; Hildesheim, Allan; Kreimer, Aimee R.] NCI, NIH, Bethesda, MD 20892 USA. [Gonzalez, Paula; Cecilia Rodriguez, Ana; Porras, Carolina; Jimenez, Silvia] Fdn INCIENSA, Proyecto Epidemiol Guanacaste, San Jose, Costa Rica. [Gonzalez, Paula; Herrero, Rolando] Int Agcy Res Canc, Prevent & Implementat Grp, F-69372 Lyon, France. [van Doorn, Leen-Jan; Struijk, Linda; Quint, Wim] DDL Diagnost Lab, Rijswijk, Netherlands. [Chen, Sabrina; DelVecchio, Corey] Informat Management Serv Inc, Calverton, MD USA. RP Kuhs, KAL (reprint author), NCI, Infect & Immunoepidemiol Branch, Div Canc Epidemiol & Genet, 9609 Med Ctr Dr,Rm 6 E210, Bethesda, MD 20892 USA. EM krystle.kuhs@nih.gov RI Schiffman, Mark/B-9766-2015; Hildesheim, Allan/B-9760-2015; Kreimer, Aimee/H-1687-2015 OI Hildesheim, Allan/0000-0003-0257-2363; FU NCI [N01-CP-11005]; National Institutes of Health Office of Research on Women's Health FX This work was supported by the NCI (contract N01-CP-11005), with funding support from the National Institutes of Health Office of Research on Women's Health. The Costa Rica HPV Vaccine Trial is a long-standing collaboration between investigators in Costa Rica and the NCI. NR 29 TC 8 Z9 8 U1 0 U2 2 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0022-1899 EI 1537-6613 J9 J INFECT DIS JI J. Infect. Dis. PD DEC 15 PY 2014 VL 210 IS 12 BP 1890 EP 1899 DI 10.1093/infdis/jiu357 PG 10 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA AU7HK UT WOS:000345771200007 ER PT J AU Ocholla, H Preston, MD Mipando, M Jensen, ATR Campino, S MacInnis, B Alcock, D Terlouw, A Zongo, I Oudraogo, JB Djimde, AA Assefa, S Doumbo, OK Borrmann, S Nzila, A Marsh, K Fairhurst, RM Nosten, F Anderson, TJC Kwiatkowski, DP Craig, A Clark, TG Montgomery, J AF Ocholla, Harold Preston, Mark D. Mipando, Mwapatsa Jensen, Anja T. R. Campino, Susana MacInnis, Bronwyn Alcock, Daniel Terlouw, Anja Zongo, Issaka Oudraogo, Jean-Bosco Djimde, Abdoulaye A. Assefa, Samuel Doumbo, Ogobara K. Borrmann, Steffen Nzila, Alexis Marsh, Kevin Fairhurst, Rick M. Nosten, Francois Anderson, Tim J. C. Kwiatkowski, Dominic P. Craig, Alister Clark, Taane G. Montgomery, Jacqui TI Whole-Genome Scans Provide Evidence of Adaptive Evolution in Malawian Plasmodium falciparum Isolates SO JOURNAL OF INFECTIOUS DISEASES LA English DT Article DE Plasmodium falciparum; genomes; genetic epidemiology; Malawi ID MALARIA PARASITES; CHLOROQUINE RESISTANCE; DNA POLYMORPHISM; SELECTION; GENES; POPULATIONS; DIVERSITY; ENDEMICITY; INDEXES; RETURN AB Selection by host immunity and antimalarial drugs has driven extensive adaptive evolution in Plasmodium falciparum and continues to produce ever-changing landscapes of genetic variation. We performed whole-genome sequencing of 69 P. falciparum isolates from Malawi and used population genetics approaches to investigate genetic diversity and population structure and identify loci under selection. High genetic diversity (pi = 2.4 x 10(-4)), moderately high multiplicity of infection (2.7), and low linkage disequilibrium (500-bp) were observed in Chikhwawa District, Malawi, an area of high malaria transmission. Allele frequency-based tests provided evidence of recent population growth in Malawi and detected potential targets of host immunity and candidate vaccine antigens. Comparison of the sequence variation between isolates from Malawi and those from 5 geographically dispersed countries (Kenya, Burkina Faso, Mali, Cambodia, and Thailand) detected population genetic differences between Africa and Asia, within Southeast Asia, and within Africa. Haplotype-based tests of selection to sequence data from all 6 populations identified signals of directional selection at known drug-resistance loci, including pfcrt, pfdhps, pfmdr1, and pfgch1. The sequence variations observed at drug-resistance loci reflect differences in each country's historical use of antimalarial drugs and may be useful in formulating local malaria treatment guidelines. C1 [Ocholla, Harold; Terlouw, Anja; Montgomery, Jacqui] Univ Malawi, Coll Med, Malawi Liverpool Wellcome Trust Clin Res Programm, Blantyre, Malawi. [Mipando, Mwapatsa] Univ Malawi, Coll Med, Dept Physiol, Blantyre, Malawi. [Ocholla, Harold; Terlouw, Anja; Craig, Alister; Montgomery, Jacqui] Univ Liverpool, Liverpool Sch Trop Med, Liverpool L3 5QA, Merseyside, England. [Preston, Mark D.; Assefa, Samuel; Clark, Taane G.] London Sch Hyg & Trop Med, Fac Infect & Trop Dis, London, England. [Campino, Susana; MacInnis, Bronwyn; Alcock, Daniel; Djimde, Abdoulaye A.; Kwiatkowski, Dominic P.] Wellcome Trust Sanger Inst, Hinxton, Cambs, England. [Kwiatkowski, Dominic P.] Univ Oxford, Wellcome Trust Ctr Human Genet, Oxford OX1 2JD, England. [Jensen, Anja T. R.] Univ Copenhagen, Dept Int Hlth Immunol & Microbiol, Ctr Med Parasitol, DK-1168 Copenhagen, Denmark. [Jensen, Anja T. R.] Copenhagen Univ Hosp, Dept Infect Dis, Copenhagen, Denmark. [Zongo, Issaka; Oudraogo, Jean-Bosco] Inst Rech Sci St, Bobo Dioulasso, Burkina Faso. [Djimde, Abdoulaye A.; Doumbo, Ogobara K.] Univ Bamako, Malaria Res & Training Ctr, Fac Med Pharm & Dent, Bamako, Mali. [Borrmann, Steffen] Univ Tubingen, Inst Trop Med, Tubingen, Germany. [Nzila, Alexis] King Fahd Univ Petr & Minerals, Dept Biol, Dhahran, Saudi Arabia. [Marsh, Kevin] KEMRI Wellcome Trust Res Programme, Kilifi, Kenya. [Fairhurst, Rick M.] NIAID, Lab Malaria & Vector Res, NIH, Bethesda, MD 20892 USA. [Anderson, Tim J. C.] Texas Biomed Res Inst, San Antonio, TX USA. [Nosten, Francois] Univ Oxford, Nuffield Dept Med, Ctr Trop Med, Oxford OX1 2JD, England. [Nosten, Francois] Mahidol Univ, Fac Trop Med, Shoklo Malaria Res Unit, Mahidol Oxford Trop Med Res Unit, Mae Sot, Thailand. RP Ocholla, H (reprint author), KEMRI CDC Labs, Kisumu, Kenya. EM ocholla@me.com RI Preston, Mark/P-1429-2015; OI Preston, Mark/0000-0002-6506-3104; Borrmann, Steffen/0000-0001-9189-4393; Ramstedt Jensen, Anja Tatiana/0000-0002-4004-7554; Craig, Alister/0000-0003-0914-6164; Kwiatkowski, Dominic/0000-0002-5023-0176; Mead, Daniel/0000-0001-7717-4330 FU Wellcome Trust [WT084289MA, 080964, 077012/Z/05/Z, 098051, 090770/Z/09/Z]; Medical Research Council UK [MR/K000551/1]; Intramural Research Program, National Institute of Allergy and Infectious Diseases, National Institutes of Health FX This work was supported by the Wellcome Trust (grant WT084289MA to H. O., on behalf of the Malaria Capacity Development Consortium; fellowship grant 080964 to J. M.; core support grants 077012/Z/05/Z, 098051 [to the Wellcome Trust Sanger Institute] and 090770/Z/09/Z [to the Resource Centre for Genomic Epidemiology of Malaria]); and a core grant to the Malawi-Liverpool-Wellcome Trust Programme), the Medical Research Council UK (grant MR/K000551/1 to T. G. C. and M. D. P.), and the Intramural Research Program, National Institute of Allergy and Infectious Diseases, National Institutes of Health. NR 48 TC 11 Z9 11 U1 0 U2 37 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0022-1899 EI 1537-6613 J9 J INFECT DIS JI J. Infect. Dis. PD DEC 15 PY 2014 VL 210 IS 12 BP 1991 EP 2000 DI 10.1093/infdis/jiu349 PG 10 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA AU7HK UT WOS:000345771200018 PM 24948693 ER PT J AU Jozwiak, K Targowska-Duda, KM Kaczor, AA Kozak, J Ligeza, A Szacon, E Wrobel, TM Budzynska, B Biala, G Fornal, E Poso, A Wainer, IW Matosiuk, D AF Jozwiak, Krzysztof Targowska-Duda, Katarzyna M. Kaczor, Agnieszka A. Kozak, Joanna Ligeza, Agnieszka Szacon, Elzbieta Wrobel, Tomasz M. Budzynska, Barbara Biala, Grazyna Fornal, Emilia Poso, Antti Wainer, Irving W. Matosiuk, Dariusz TI Synthesis, in vitro and in vivo studies, and molecular modeling of N-alkylated dextromethorphan derivatives as non-competitive inhibitors of alpha(3)beta(4) nicotinic acetylcholine receptor SO BIOORGANIC & MEDICINAL CHEMISTRY LA English DT Article DE Dextromethorphan; Nicotinic acetylcholine receptors; Non-competitive inhibitors; alpha 3 beta 4 nicotinic acetylcholine receptor ID CONDITIONED PLACE PREFERENCE; BINDING-SITES; ELECTRON-TRANSFER; TERTIARY-AMINES; LIGAND-BINDING; HIGH-AFFINITY; MORPHINE; BRAIN; RATS; MICE AB 9 N-alkylated derivatives of dextromethorphan are synthesized and studied as non-competitive inhibitors of alpha 3 beta 4 nicotinic acetylcholine receptors (nAChRs). In vitro activity towards alpha 3 beta 4 nicotinic acetylcholine receptor is determined using a patch-clamp technique and is in the micromolar range. Homology modeling, molecular docking and molecular dynamics of ligand-receptor complexes in POPC membrane are used to find the mode of interactions of N-alkylated dextromethorphan derivatives with alpha 3 beta 4 nAChR. The compounds, similarly as dextromethorphan, interact with the middle portion of a3b4 nAChR ion channel. Finally, behavioral tests confirmed potential application of the studied compounds for the treatment of addiction. (C) 2014 Elsevier Ltd. All rights reserved. C1 [Jozwiak, Krzysztof; Targowska-Duda, Katarzyna M.; Kozak, Joanna] Med Univ Lublin, Dept Chem, Lab Med Chem & Neuroengn, PL-20093 Lublin, Poland. [Kaczor, Agnieszka A.; Ligeza, Agnieszka; Szacon, Elzbieta; Wrobel, Tomasz M.; Matosiuk, Dariusz] Fac Pharm, Div Med Analyt, Comp Modeling Lab, Dept Synth & Chem Technol Pharmaceut Subst, PL-20093 Lublin, Poland. [Kaczor, Agnieszka A.; Poso, Antti] Univ Eastern Finland, Sch Pharm, FI-70211 Kuopio, Finland. [Kozak, Joanna] Med Univ Lublin, Dept Anat, PL-20090 Lublin, Poland. [Budzynska, Barbara; Biala, Grazyna] Med Univ Lublin, Dept Pharmacol & Pharmacodynam, PL-20093 Lublin, Poland. [Fornal, Emilia] Catholic Univ Lublin, Dept Chem, PL-20718 Lublin, Poland. [Wainer, Irving W.] NIA, Clin Invest Lab, Div Intramural Res Programs, NIH, Baltimore, MD 21224 USA. RP Matosiuk, D (reprint author), Fac Pharm, Div Med Analyt, Comp Modeling Lab, Dept Synth & Chem Technol Pharmaceut Subst, 4a Chodzki St, PL-20093 Lublin, Poland. EM darek.matosiuk@umlub.pl RI Targowska-Duda, Katarzyna/I-3434-2016; Kaczor, Agnieszka Anna/A-3744-2015; OI Kaczor, Agnieszka Anna/0000-0001-8679-9623; Poso, Antti/0000-0003-4196-4204 FU Intramural Research Program of the National Institute on Aging/ NIH; Foundation For Polish Science [TEAM 2009-4/5]; Polish Ministry for Science and Higher Education [N N405 0633 34] FX The paper was developed using the equipment purchased within the project ` The equipment of innovative laboratories doing research on new medicines used in the therapy of civilization and neoplastic diseases' within the Operational Program Development of Eastern Poland 2007- 2013, Priority Axis I modern Economy, operations I. 3 Innovation promotion. The research was partially performed during the postdoctoral Marie Curie fellowship of Dr. Agnieszka A. Kaczor at University of Eastern Finland, Kuopio, Finland, and during the scholar visit of Dr. Katarzyna TargowskaDuda at this University. The work was supported by funds from the Intramural Research Program of the National Institute on Aging/ NIH and the Foundation For Polish Science (TEAM 2009-4/5 and FOCUS 4/2006 programmes), and Polish Ministry for Science and Higher Education ( grant number N N405 0633 34). Calculations were partially were performed under a computational grant by Interdisciplinary Center for Mathematical and Computational Modeling ( ICM), Warsaw, Poland, grant number G30- 18 and under resources and licenses from CSC, Finland. The authors wish to thank Dr. Lawrence Toll for critical reading and valuable suggestion to the work. NR 42 TC 2 Z9 2 U1 0 U2 19 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0968-0896 EI 1464-3391 J9 BIOORGAN MED CHEM JI Bioorg. Med. Chem. PD DEC 15 PY 2014 VL 22 IS 24 BP 6846 EP 6856 DI 10.1016/j.bmc.2014.10.036 PG 11 WC Biochemistry & Molecular Biology; Chemistry, Medicinal; Chemistry, Organic SC Biochemistry & Molecular Biology; Pharmacology & Pharmacy; Chemistry GA AU5MJ UT WOS:000345650800013 PM 25464883 ER PT J AU Massilamany, C Gangaplara, A Reddy, J AF Massilamany, Chandirasegaran Gangaplara, Arunakumar Reddy, Jay TI Intricacies of cardiac damage in coxsackievirus B3 infection: Implications for therapy SO INTERNATIONAL JOURNAL OF CARDIOLOGY LA English DT Review DE Heart; Viral myocarditis; Coxsackievirus; Autoimmunity ID EXPERIMENTAL AUTOIMMUNE MYOCARDITIS; ACUTE VIRAL MYOCARDITIS; NATURAL-KILLER-CELLS; REGULATORY T-CELLS; EXPERIMENTAL MURINE MYOCARDITIS; LINKED DILATED CARDIOMYOPATHY; HEART-SPECIFIC AUTOANTIBODIES; VIRUS B3-INDUCED MYOCARDITIS; LEFT-VENTRICULAR DYSFUNCTION; ENCODED PROTEASE 3C(PRO) AB Heart disease is the leading cause of death in humans, and myocarditis is one predominant cause of heart failure in young adults. Patients affected with myocarditis can develop dilated cardiomyopathy (DCM), a common reason for heart transplantation, which to date is the only viable option for combatting DCM. Myocarditis/DCM patients show antibodies to coxsackievirus B (CVB)3 and cardiac antigens, suggesting a role for CVB-mediated autoimmunity in the disease pathogenesis; however, a direct causal link remains to be determined clinically. Experimentally, myocarditis can be induced in susceptible strains of mice using the human isolates of CVB3, and the disease pathogenesis of postinfectious myocarditis resembles that of human disease, making the observations made in animals relevant to humans. In this review, we discuss the complex nature of CVB3-induced myocarditis as it relates to the damage caused by both the virus and the host's response to infection. Based on recent data we obtained in the mouse model of CVB3 infection, we provide evidence to suggest that CVB3 infection accompanies the generation of cardiac myosin-specific CD4 T cells that can transfer the disease to naive recipients. The therapeutic implications of these observations are also discussed. (C) 2014 Elsevier Ireland Ltd. All rights reserved. C1 [Massilamany, Chandirasegaran; Reddy, Jay] Univ Nebraska, Sch Vet Med & Biomed Sci, Lincoln, NE 68583 USA. [Gangaplara, Arunakumar] NIAID, Immunol Lab, NIH, Bethesda, MD 20892 USA. RP Reddy, J (reprint author), Univ Nebraska, Sch Vet Med & Biomed Sci, Room 202,Bldg VBS, Lincoln, NE 68583 USA. EM nreddy2@unl.edu RI Massilamany, Chandirasegaran/D-9305-2016; OI Massilamany, Chandirasegaran/0000-0002-0205-282X; Gangaplara, Arunakumar/0000-0001-6307-9391 FU National Institutes of Health [HL114669]; Myocarditis Foundation, NJ. FX This work was supported by the National Institutes of Health (HL114669). CM is a recipient of a postdoctoral research fellowship grant awarded by the Myocarditis Foundation, NJ. NR 182 TC 4 Z9 4 U1 2 U2 7 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0167-5273 EI 1874-1754 J9 INT J CARDIOL JI Int. J. Cardiol. PD DEC 15 PY 2014 VL 177 IS 2 BP 330 EP 339 DI 10.1016/j.ijcard.2014.09.136 PG 10 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA AT9FB UT WOS:000345232200024 PM 25449464 ER PT J AU Vyas, NS Ahn, K Stahl, DR Caviston, P Simic, M Netherwood, S Puri, BK Lee, Y Aitchison, KJ AF Vyas, Nora S. Ahn, Kwangmi Stahl, Daniel R. Caviston, Paul Simic, Mima Netherwood, Siobhan Puri, Basant K. Lee, Yohan Aitchison, Katherine J. TI Association of KIBRA rs17070145 polymorphism with episodic memory in the early stages of a human neurodevelopmental disorder SO PSYCHIATRY RESEARCH LA English DT Article DE Adolescent; KIBRA; Schizophrenia; WWC1 protein; Memory; Polymorphism ID CHILDHOOD-ONSET SCHIZOPHRENIA; VISUAL SUSTAINED ATTENTION; COGNITIVE DEFICITS; NONPSYCHOTIC SIBLINGS; VERBAL MEMORY; SPECTRUM DISORDERS; GENE VARIANTS; METAANALYSIS; IMPAIRMENT; PERFORMANCE AB A common T/C polymorphism within the ninth intron of the KIBRA gene (rs17070145) is thought to influence memory in humans. Since cognitive impairment, including memory, is a core feature of schizophrenia, we attempted to investigate this association in an independent sample of adolescent patients with early-onset schizophrenia (EOS; onset before age 18) probands and their healthy siblings. In a sample of 25 pairs of EOS proband-healthy full sibling, we sought to investigate the association of KIBRA with memory performance. Episodic memory was measured using immediate and delayed recall measures of the California Verbal Learning Test. EOS underperformed at immediate and delayed recall compared with siblings. In a combined analysis (TT vs. TC/CC) assuming a C dominant model of inheritance, we found a main effect of genotype where individuals with TT genotype outperformed non-TT-carriers at immediate and delayed recall. A genotype by group interaction showed that EOS with IT genotype did not show a memory advantage over siblings with TT or non-TT-carriers at immediate or delayed recall. Siblings with TT genotype showed enhanced immediate recall (not delayed recall) compared with non-TT-carriers. This study demonstrates an association between the KIBRA gene and episodic memory (immediate free recall) and suggests a differential effect of this genetic variant in EOS and healthy siblings. (C) 2014 Elsevier Ireland Ltd. All rights reserved. C1 [Vyas, Nora S.] Kingston Univ London, Dept Psychol, Kingston KT1 2EE, Surrey, England. [Vyas, Nora S.; Ahn, Kwangmi; Lee, Yohan] NIMH, NIH, Child Psychiat Branch, Bethesda, MD 20892 USA. [Vyas, Nora S.; Aitchison, Katherine J.] Kings Coll London, Inst Psychiat, MRC SGDP Ctr, London SE5 8AF, England. [Stahl, Daniel R.] Kings Coll London, NIHR Biomed Res Ctr Mental Hlth, Dept Biostat, London SE5 8AF, England. [Stahl, Daniel R.] Kings Coll London, Inst Psychiat, Dept Biostat, London SE5 8AF, England. [Caviston, Paul] North East London NHS Fdn Trust, Child & Adolescent Mental Hlth Serv, London IG3 8XQ, Essex, England. [Simic, Mima] South London & Maudsley NHS Fdn Trust, CAMHS Natl & Specialist Serv, London SE5 8AF, England. [Netherwood, Siobhan] South London & Maudsley NHS Fdn Trust, CAMHS, London CR0 1QG, England. [Puri, Basant K.] Univ London Imperial Coll Sci Technol & Med, Dept Med, London W12 0HS, England. [Aitchison, Katherine J.] Univ Alberta, Dept Psychiat & Med Genet, Edmonton, AB T6G 2E1, Canada. RP Vyas, NS (reprint author), NIMH, NIH, Child Psychiat Branch, 10 Ctr Dr,Bldg 10,Room 3N202, Bethesda, MD 20892 USA. EM nora.vyas@nih.gov RI Stahl, Daniel/B-9713-2011; Aitchison, Katherine/G-4476-2013 OI Stahl, Daniel/0000-0001-7987-6619; Aitchison, Katherine/0000-0002-1107-3024 NR 75 TC 2 Z9 2 U1 6 U2 8 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0165-1781 J9 PSYCHIAT RES JI Psychiatry Res. PD DEC 15 PY 2014 VL 220 IS 1-2 BP 37 EP 43 DI 10.1016/j.psychres.2014.07.024 PG 7 WC Psychiatry SC Psychiatry GA AT6OJ UT WOS:000345058400005 PM 25146696 ER PT J AU Lardinois, O Kirby, PJ Morgan, DL Sills, RC Tomer, KB Deterding, LJ AF Lardinois, O. Kirby, P. J. Morgan, D. L. Sills, R. C. Tomer, K. B. Deterding, L. J. TI Mass spectrometric analysis of rat cerebrospinal fluid proteins following exposure to the neurotoxicant carbonyl sulfide SO RAPID COMMUNICATIONS IN MASS SPECTROMETRY LA English DT Article ID BIOMARKER DISCOVERY; ALZHEIMERS-DISEASE; LUMBAR PUNCTURE; F344 RATS; PROTEOMICS; CSF; IDENTIFICATION; EXPRESSION; DIAGNOSIS; BRAIN AB RATIONALE: Using a proteomic-based approach we have investigated possible altered expression of a range of cerebral spinal fluid (CSF) proteins following exposure to the neurotoxicant carbonyl sulfide (COS). CSF is ideal for the investigation of markers of brain injury or disease since it is secreted from several central nervous system structures and changes in the CSF composition may reflect brain insult and many pathological processes. METHODS: Animals were placed in exposure chambers and were exposed to 0 ppm or 500 ppm COS for 1, 2 or 3 days, 6 h per day. After the last inhalation exposure, 50-70 mu LCSF sample was obtained by lumbar puncture. CSF samples were analyzed by electrospray ionization mass spectrometry (ESI-MS) on either a Premier quadrupole time-of-flight (QTOF) or an Agilent 6340 ion trap and by matrix-assisted laser desorption/ionization (MALDI)-MS on a 4800 MALDI-TOF/TOF analyzer. RESULTS: The dynamic range of abundance of the identified proteins spanned over more than three orders of magnitude. The four most abundant proteins identified (albumin, cystatin C, serotransferrin, transthyretin) are major proteins that are present in both CSF and blood at high levels but the fifth most abundant protein identified (prostaglandin H2D isomerase) is the second most abundant protein in human CSF and is secreted and synthesized in the rat central nervous system. No significant differences were observed between COS-treated CSF samples and the control CSF samples because of blood contamination. CONCLUSIONS: Quantitative MS protein analyses of rat CSF is limited by the low sample volumes that can practicably be obtained from rats and the low protein concentrations in rat CSF. Results of this work suggest a clear need for CSF collection that would minimize blood contamination. Published in 2014. This article is a U. S. Government work and is in the public domain in the USA. C1 [Lardinois, O.; Tomer, K. B.; Deterding, L. J.] NIEHS, Struct Biol Lab, NIH, DHHS, Res Triangle Pk, NC 27709 USA. [Kirby, P. J.; Morgan, D. L.] NIEHS, Lab Toxicol & Pharmacol, NIH, DHHS, Res Triangle Pk, NC 27709 USA. [Sills, R. C.] NIEHS, NIH, DHHS, Res Triangle Pk, NC 27709 USA. RP Deterding, LJ (reprint author), NIEHS, Struct Biol Lab, NIH, 111 TW Alexander Dr, Res Triangle Pk, NC 27709 USA. EM deterdi2@niehs.nih.gov FU NIH, National Institute of Environmental Health Sciences FX This research has been supported by the Intramural Research Program of the NIH, National Institute of Environmental Health Sciences. The authors would like to acknowledge Dr. Jeffrey Kuhn (NIEHS/NIH) and Dr. Jason Williams (NIEHS/NIH) for critical review of the manuscript, and the NIEHS Protein Microcharacterization Core Facility for helpful suggestions and assistance. NR 33 TC 3 Z9 3 U1 0 U2 14 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0951-4198 EI 1097-0231 J9 RAPID COMMUN MASS SP JI Rapid Commun. Mass Spectrom. PD DEC 15 PY 2014 VL 28 IS 23 BP 2531 EP 2538 DI 10.1002/rcm.7046 PG 8 WC Biochemical Research Methods; Chemistry, Analytical; Spectroscopy SC Biochemistry & Molecular Biology; Chemistry; Spectroscopy GA AT0HH UT WOS:000344617100006 PM 25366400 ER PT J AU Best, RB Miller, C Mittal, J AF Best, Robert B. Miller, Cayla Mittal, Jeetain TI Role of solvation in pressure-induced helix stabilization SO JOURNAL OF CHEMICAL PHYSICS LA English DT Article ID MOLECULAR-DYNAMICS; COIL TRANSITION; INTERNAL CAVITIES; PROTEIN-STRUCTURE; TRP-CAGE; STABILITY; POLYPEPTIDES; SIMULATIONS; PEPTIDE; MODEL AB In contrast to the well-known destabilization of globular proteins by high pressure, recent work has shown that pressure stabilizes the formation of isolated a-helices. However, all simulations to date have obtained a qualitatively opposite result within the experimental pressure range. We show that using a protein force field (Amber03w) parametrized in conjunction with an accurate water model (TIP4P/2005) recovers the correct pressure-dependence and an overall stability diagram for helix formation similar to that from experiment; on the other hand, we confirm that using TIP3P water results in a very weak pressure destabilization of helices. By carefully analyzing the contributing factors, we show that this is not merely a consequence of different peptide conformations sampled using TIP3P. Rather, there is a critical role for the solvent itself in determining the dependence of total system volume (peptide and solvent) on helix content. Helical peptide structures exclude a smaller volume to water, relative to non-helical structures with both the water models, but the total system volume for helical conformations is higher than non-helical conformations with TIP3P water at low to intermediate pressures, in contrast to TIP4P/ 2005 water. Our results further emphasize the importance of using an accurate water model to study protein folding under conditions away from standard temperature and pressure. (C) 2014 AIP Publishing LLC. C1 [Best, Robert B.] NIDDKD, Lab Chem Phys, NIH, Bethesda, MD 20892 USA. [Miller, Cayla; Mittal, Jeetain] Lehigh Univ, Dept Chem & Biomol Engn, Bethlehem, PA 18015 USA. RP Best, RB (reprint author), NIDDKD, Lab Chem Phys, NIH, Bethesda, MD 20892 USA. EM robertbe@helix.nih.gov; jeetain@lehigh.edu RI Best, Robert/H-7588-2016; OI Best, Robert/0000-0002-7893-3543; Mittal, Jeetain/0000-0002-9725-6402 FU Intramural Research Program of the National Institute of Diabetes and Digestive and Kidney Diseases of the National Institutes of Health; Alfred P. Sloan Foundation Research Fellowship; National Science Foundation [TG-MCB-120014] FX R.B. is supported by the Intramural Research Program of the National Institute of Diabetes and Digestive and Kidney Diseases of the National Institutes of Health. J.M. is supported by Alfred P. Sloan Foundation Research Fellowship. 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) and the high-performance computing capabilities of the Extreme Science and Engineering Discovery Environment (XSEDE), which is supported by the National Science Foundation (Grant No. TG-MCB-120014). NR 34 TC 5 Z9 5 U1 5 U2 21 PU AMER INST PHYSICS PI MELVILLE PA 1305 WALT WHITMAN RD, STE 300, MELVILLE, NY 11747-4501 USA SN 0021-9606 EI 1089-7690 J9 J CHEM PHYS JI J. Chem. Phys. PD DEC 14 PY 2014 VL 141 IS 22 AR 22D522 DI 10.1063/1.4901112 PG 7 WC Chemistry, Physical; Physics, Atomic, Molecular & Chemical SC Chemistry; Physics GA AW4TH UT WOS:000346272800069 PM 25494793 ER PT J AU Yun, S Yun, S AF Yun, Sajung Yun, Sijung TI Masking as an effective quality control method for next-generation sequencing data analysis SO BMC BIOINFORMATICS LA English DT Article DE NGS; Preprocessing; Masking; Trimming ID READ ALIGNMENT; FRAMEWORK AB Background: Next generation sequencing produces base calls with low quality scores that can affect the accuracy of identifying simple nucleotide variation calls, including single nucleotide polymorphisms and small insertions and deletions. Here we compare the effectiveness of two data preprocessing methods, masking and trimming, and the accuracy of simple nucleotide variation calls on whole-genome sequence data from Caenorhabditis elegans. Masking substitutes low quality base calls with 'N's (undetermined bases), whereas trimming removes low quality bases that results in a shorter read lengths. Results: We demonstrate that masking is more effective than trimming in reducing the false-positive rate in single nucleotide polymorphism (SNP) calling. However, both of the preprocessing methods did not affect the false-negative rate in SNP calling with statistical significance compared to the data analysis without preprocessing. False-positive rate and false-negative rate for small insertions and deletions did not show differences between masking and trimming. Conclusions: We recommend masking over trimming as a more effective preprocessing method for next generation sequencing data analysis since masking reduces the false-positive rate in SNP calling without sacrificing the false-negative rate although trimming is more commonly used currently in the field. C1 [Yun, Sajung] Univ Hawaii Manoa, John A Burns Sch Med, Honolulu, HI 96822 USA. [Yun, Sijung] NIDDK, Mol Biol Lab, NIH, Bethesda, MD 20892 USA. RP Yun, S (reprint author), NIDDK, Mol Biol Lab, NIH, Bethesda, MD 20892 USA. EM yuns@mail.nih.gov FU National Institutes of Health (NIH), National Institute of Diabetes and Digestive and Kidney Diseases FX The work was supported by the Intramural Research Program of the National Institutes of Health (NIH), National Institute of Diabetes and Digestive and Kidney Diseases (Sijung Yun). NR 15 TC 1 Z9 1 U1 0 U2 4 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1471-2105 J9 BMC BIOINFORMATICS JI BMC Bioinformatics PD DEC 13 PY 2014 VL 15 AR 382 DI 10.1186/s12859-014-0382-2 PG 8 WC Biochemical Research Methods; Biotechnology & Applied Microbiology; Mathematical & Computational Biology SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Mathematical & Computational Biology GA AW8LL UT WOS:000346513300001 PM 25494997 ER PT J AU Li, MD Wang, J Niu, TH Ma, JZ Seneviratne, C Ait-Daoud, N Saadvandi, J Morris, R Weiss, D Campbell, J Haning, W Mawhinney, DJ Weis, D McCann, M Stock, C Kahn, R Iturriaga, E Yu, E Elkashef, A Johnson, BA AF Li, Ming D. Wang, Ju Niu, Tianhua Ma, Jennie Z. Seneviratne, Chamindi Ait-Daoud, Nassima Saadvandi, Jim Morris, Rana Weiss, David Campbell, Jan Haning, William Mawhinney, David J. Weis, Denis McCann, Michael Stock, Christopher Kahn, Roberta Iturriaga, Erin Yu, Elmer Elkashef, Ahmed Johnson, Bankole A. TI Transcriptome profiling and pathway analysis of genes expressed differentially in participants with or without a positive response to topiramate treatment for methamphetamine addiction SO BMC MEDICAL GENOMICS LA English DT Article DE Topiramate; Pharmacogenetics; Genes; Pathways; Transcriptome; Addiction treatment; Methamphetamine addiction ID RANDOMIZED CONTROLLED-TRIAL; MICROARRAY DATA-ANALYSIS; HUMAN BLOOD; BEHAVIORAL SENSITIZATION; DEPENDENT INDIVIDUALS; MOLECULAR-MECHANISMS; OXIDATIVE STRESS; ORAL TOPIRAMATE; PROBE LEVEL; RAT-BRAIN AB Background: Developing efficacious medications to treat methamphetamine dependence is a global challenge in public health. Topiramate (TPM) is undergoing evaluation for this indication. The molecular mechanisms underlying its effects are largely unknown. Examining the effects of TPM on genome-wide gene expression in methamphetamine addicts is a clinically and scientifically important component of understanding its therapeutic profile. Methods: In this double-blind, placebo-controlled clinical trial, 140 individuals who met the DSM-IV criteria for methamphetamine dependence were randomized to receive either TPM or placebo, of whom 99 consented to participate in our genome-wide expression study. The RNA samples were collected from whole blood for 50 TPM- and 49 placebo-treated participants at three time points: baseline and the ends of weeks 8 and 12. Genome-wide expression profiles and pathways of the two groups were compared for the responders and non-responders at Weeks 8 and 12. To minimize individual variations, expression of all examined genes at Weeks 8 and 12 were normalized to the values at baseline prior to identification of differentially expressed genes and pathways. Results: At the single-gene level, we identified 1054, 502, 204, and 404 genes at nominal P values < 0.01 in the responders vs. non-responders at Weeks 8 and 12 for the TPM and placebo groups, respectively. Among them, expression of 159, 38, 2, and 21 genes was still significantly different after Bonferroni corrections for multiple testing. Many of these genes, such as GRINA, PRKACA, PRKCI, SNAP23, and TRAK2, which are involved in glutamate receptor and GABA receptor signaling, are direct targets for TPM. In contrast, no TPM drug targets were identified in the 38 significant genes for the Week 8 placebo group. Pathway analyses based on nominally significant genes revealed 27 enriched pathways shared by the Weeks 8 and 12 TPM groups. These pathways are involved in relevant physiological functions such as neuronal function/synaptic plasticity, signal transduction, cardiovascular function, and inflammation/immune function. Conclusion: Topiramate treatment of methamphetamine addicts significantly modulates the expression of genes involved in multiple biological processes underlying addiction behavior and other physiological functions. C1 [Li, Ming D.; Wang, Ju; Niu, Tianhua; Ma, Jennie Z.; Ait-Daoud, Nassima] Univ Virginia, Dept Psychiat & Neurobehav Sci, Charlottesville, VA 22904 USA. [Saadvandi, Jim; Morris, Rana] Informat Management Consultants, Reston, VA USA. [Campbell, Jan] Univ Missouri, Dept Psychiat, Kansas City, MO 65211 USA. [Haning, William] Pacif Addict Res Ctr, Honolulu, HI USA. [Weiss, David] South Bay Treatment Ctr, San Diego, CA USA. [Weis, Denis] Lutheran Hosp Off Res, Des Moines, IA USA. [McCann, Michael] Matrix Inst Addict, West Los Angeles, CA USA. [Stock, Christopher] Salt Lake City Hlth Care Syst, Dept Vet Affairs, Salt Lake City, UT USA. [Kahn, Roberta; Iturriaga, Erin; Elkashef, Ahmed] NIDA, Div Pharmacotherapies & Med Consequences Drug, Bethesda, MD 20892 USA. [Yu, Elmer] Veterans Adm Med Ctr, Philadelphia, PA USA. [Seneviratne, Chamindi; Johnson, Bankole A.] Univ Maryland, Dept Psychiat, Baltimore, MD 21201 USA. [Weiss, David] Program Coordinat Ctr, Dept Vet Affairs Cooperat Studies, Perry Point, MD USA. RP Li, MD (reprint author), Univ Virginia, Dept Psychiat & Neurobehav Sci, Charlottesville, VA 22904 USA. EM Ming_Li@virginia.edu FU National Institute on Drug Abuse through the Department of Veterans Affairs Cooperative Studies Program [Y1-DA4006]; NIH [DA-137873] FX The clinical trial data used for this study are registered in Clinicaltrials.gov with the identifier: NCT00345371. We are grateful for the invaluable contributions of clinical information and blood samples by all participants in this clinical trial, as well as the dedicated work of many research staff at the clinical sites. We are grateful to the National Institute on Drug Abuse for its generous support through the Department of Veterans Affairs Cooperative Studies Program (Interagency Agreement No. Y1-DA4006). In addition, statistical and bioinformatics analyses of expression data were in part supported by NIH grant DA-137873 to MDL and an NIH contract to IMC. NR 65 TC 3 Z9 3 U1 2 U2 7 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1755-8794 J9 BMC MED GENOMICS JI BMC Med. Genomics PD DEC 12 PY 2014 VL 7 AR 65 DI 10.1186/s12920-014-0065-x PG 15 WC Genetics & Heredity SC Genetics & Heredity GA AZ7KP UT WOS:000348398300001 PM 25495887 ER PT J AU Jiang, ZP Lee, JC AF Jiang, Zhiping Lee, Jennifer C. TI Lysophospholipid-Containing Membranes Modulate the Fibril Formation of the Repeat Domain of a Human Functional Amyloid, Pmel17 SO JOURNAL OF MOLECULAR BIOLOGY LA English DT Article ID PINK-EYED DILUTION; ALPHA-SYNUCLEIN; BETA-PEPTIDE; SURFACTANT INTERACTIONS; AGGREGATION KINETICS; 17 SILVER; PROTEIN; MELANOSOMES; PH; LYSOLECITHIN AB Pmel17 is an important protein for pigmentation in human skin and eyes. Proteolytic fragments from Pme117 form fibrils upon which melanin is deposited in melanosomes. The repeat domain (RPT) derived from Pme117 only forms fibrils under acidic melanosomal conditions. Here, we examined the effects of lipids on RPT aggregation to explore whether intramelanosomal vesicles can facilitate fibrillogenesis. Using transmission electron microscopy, circular dichroism, and fluorescence spectroscopy, we monitored fibril formation at the ultrastructural, secondary conformational, and local levels, respectively. Phospholipid vesicles and lysophospholipid (lysolipid) micelles were employed as membrane mimics. The surfactant-like lysolipids are particularly pertinent due to their high content in melanosomal membranes. Interestingly, RPT aggregation kinetics were influenced only by lysolipid-containing phospholipid vesicles. While both vesicles containing either anionic lysophosphatidylglycerol (LPG) or zwitterionic lysophosphatidylcholine (LPC) stimulate aggregation, LPG exerted a greater effect on reducing the apparent nucleation time. A detailed comparison showed distinct behaviors of LPG versus LPC monomers and micelles plausibly originating from their headgroup hydrogen bonding capabilities. Acceleration and retardation of aggregation were observed for LPG monomers and micelles, respectively. Because a specific interaction between LPG and RPT was identified by intrinsic W423 fluorescence and induced alpha-helical structure, it is inferred that binding of LPG near the C-terminal amyloid core initiates intermolecular association, whereas stabilization of alpha-helical conformation inhibits beta-sheet formation. Contrastingly, LPC promotes RPT aggregation at both submicellar and micellar concentrations via non-specific binding with undetectable secondary structural change. Our findings suggest that protein lysolipid interactions within melanosomes may regulate amyloid formation in vivo. Published by Elsevier Ltd. C1 [Jiang, Zhiping; Lee, Jennifer C.] NHLBI, Lab Mol Biophys, Biochem & Biophys Ctr, NIH, Bethesda, MD 20892 USA. RP Lee, JC (reprint author), Lab Mol Biophys, 50 South Dr MSC 8013, Bethesda, MD 20892 USA. EM leej4@mail.nih.gov RI Lee, Jennifer/E-9658-2015 OI Lee, Jennifer/0000-0003-0506-8349 FU Intramural Research Program at the National Institutes of Health, National Heart, Lung, and Blood Institute FX This work is supported by the Intramural Research Program at the National Institutes of Health, National Heart, Lung, and Blood Institute. We thank M. Daniels, P. Connelly (Electron Microscopy Core Facility), Y. He (Protein Expression Facility), D.-Y. Lee (Biochemistry Core Facility), and G. Piszczek (Biophysics Core Facility) for technical assistance and use of equipment. We acknowledge R. P. McGlinchey for performing Trp variant PCR and helpful discussions and S. K. Hess for manuscript proof reading. NR 63 TC 5 Z9 5 U1 1 U2 12 PU ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD PI LONDON PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND SN 0022-2836 EI 1089-8638 J9 J MOL BIOL JI J. Mol. Biol. PD DEC 12 PY 2014 VL 426 IS 24 BP 4074 EP 4086 DI 10.1016/j.jmb.2014.10.009 PG 13 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA AY6DF UT WOS:000347657000013 PM 25451784 ER PT J AU Callicrate, T Dikow, R Thomas, JW Mullikin, JC Jarvis, ED Fleischer, RC AF Callicrate, Taylor Dikow, Rebecca Thomas, James W. Mullikin, James C. Jarvis, Erich D. Fleischer, Robert C. CA NISC Comparative Sequencing TI Genomic resources for the endangered Hawaiian honeycreepers SO BMC GENOMICS LA English DT Article DE Genome; Hawaiian honeycreepers; SNP; RAD tags; Drepanidines; Hemignathus virens ID DNA-SEQUENCING DATA; MALARIA PLASMODIUM-RELICTUM; AVIAN MALARIA; GENETIC DIVERSITY; SNP DISCOVERY; LINKAGE MAP; DE-NOVO; EVOLUTION; BIRDS; PHYLOGENY AB Background: The Hawaiian honeycreepers are an avian adaptive radiation containing many endangered and extinct species. They display a dramatic range of phenotypic variation and are a model system for studies of evolution, conservation, disease dynamics and population genetics. Development of a genome-scale resources for this group would augment the quality of research focusing on Hawaiian honeycreepers and facilitate comparative avian genomic research. Results: We assembled the genome sequence of a Hawaii amakihi (Hemignathus virens), and identified similar to 3.9 million single nucleotide polymorphisms (SNPs) in the genome. Using the amakihi genome as a reference, we also identified similar to 156,000 SNPs in RAD tag (restriction site associated DNA) sequencing of five honeycreeper species (palila [Loxioides bailleui], Nihoa finch [Telespiza ultima], iiwi [Vestiaria coccinea], apapane [Himatione sanguinea], and amakihi). SNPs are distributed throughout the amakihi genome, and the individual sequenced shows several large regions of low heterozygosity on chromosomes 1, 5, 6, 8 and 11. SNPs from RAD tag sequencing were also found throughout the genome but were found to be more densely located on microchromosomes, apparently a result of differential distribution of the particular site recognized by restriction enzyme BseXI. Conclusions: The amakihi genome sequence will be useful for comparative avian genomics research and provides a significant resource for studies in such areas as disease ecology, evolution, and conservation genetics. The genome sequences will enable mapping of transcriptome data for honeycreepers and comparison of gene sequences between avian taxa. Researchers will be able to use the large number of SNP markers to genotype honeycreepers in regions of interest or across the whole genome. There are enough markers to enable use of methods such as genome-wide association studies (GWAS) that will allow researchers to make connections between phenotypic diversity of honeycreepers and specific genetic variants. Genome-wide markers will also help resolve phylogenetic and population genetic questions in honeycreepers. C1 [Callicrate, Taylor; Dikow, Rebecca; Fleischer, Robert C.] Smithsonian Conservat Biol Inst, Ctr Conservat & Evolutionary Genet, Washington, DC 20008 USA. [Callicrate, Taylor] Univ Maryland, Dept Anim & Avian Sci, College Pk, MD 20742 USA. [Thomas, James W.; Mullikin, James C.] NHGRI, NIH, Bethesda, MD 20892 USA. [Jarvis, Erich D.] Duke Univ, Med Ctr, Howard Hughes Med Inst, Dept Neurobiol, Durham, NC 27710 USA. RP Fleischer, RC (reprint author), Smithsonian Conservat Biol Inst, Ctr Conservat & Evolutionary Genet, Washington, DC 20008 USA. EM fleischerr@si.edu RI Jarvis, Erich/A-2319-2008 OI Jarvis, Erich/0000-0001-8931-5049 FU Smithsonian Institution; NHGRI Intramural Research Program; Office of the Undersecretary for Science Next Generation Sequencing Small Grants Program FX The Smithsonian Institution provided funds to R.C.F. and T.C. for this research through the Pell Competitive Grants Program for Science and the Office of the Undersecretary for Science Next Generation Sequencing Small Grants Program. J.W.T., J.C.M. and the NISC Comparative Sequencing Program were funded by the NHGRI Intramural Research Program. Samples used in this study were obtained under appropriate USFWS and Hawaii DLNR-DOFAW permits, and IACUC approvals. Bhanu Rekepalli and Amit Upadhyay from the Joint Institute for Computational Sciences group at the University of Tennessee provided scripts for comparing Stacks and amakihi genome genotypes. We thank Jason Howard of the Jarvis lab for assistance in coordinating the Roche 454 Sequencing reactions, and Roche 454 and the Duke Genome center for help in conducting the reactions. We also thank Nancy Rotzel Mclnerney of the CCEG lab for facilitating this research, Helen James for discussion and comments on the manuscript, and Jack Jeffrey for use of his photographs in Figure 4. NR 60 TC 7 Z9 7 U1 6 U2 58 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1471-2164 J9 BMC GENOMICS JI BMC Genomics PD DEC 12 PY 2014 VL 15 AR 1098 DI 10.1186/1471-2164-15-1098 PG 13 WC Biotechnology & Applied Microbiology; Genetics & Heredity SC Biotechnology & Applied Microbiology; Genetics & Heredity GA AY4WE UT WOS:000347575100002 PM 25496081 ER PT J AU Ito, Y AF Ito, Yoichiro TI Counter-current motion in counter-current chromatography SO JOURNAL OF CHROMATOGRAPHY A LA English DT Article; Proceedings Paper CT 8th International Conference on Countercurrent Chromatography (CCC) CY JUL 23-25, 2014 CL Uxbridge, ENGLAND DE Countercurrent chromatography; Liquid-liquid separations; Centrifugal separations; Terminology; Countercurrent; Stationary phase ID COIL PLANET CENTRIFUGE AB After the CCC2012 meeting, I have received an e-mail regarding the terminology of "Countercurrent Chromatography". It stated that the term "Countercurrent" is a misnomer, because its stationary phase is motionless in the column and that the method should be renamed as liquid-liquid separations or centrifugal separations. However, it was found that these names are already used for various other techniques as found via Google search. The term "Countercurrent Chromatography" was originally made after two preparative methods of Countercurrent distribution and liquid Chromatography, both having no countercurrent motion in the column. However, it is surprising to find that this F1 hybrid method "Countercurrent Chromatography" can clearly exhibit countercurrent motion within the separation column in both hydrodynamic and hydrostatic equilibrium systems. This justifies that "Countercurrent Chromatography" is a proper term for this chromatographic method. Published by Elsevier B.V. C1 NHLBI, Biochem & Biophys Ctr, Lab Bioseparat Technol, NIH, Bethesda, MD 20892 USA. RP Ito, Y (reprint author), NHLBI, Biochem & Biophys Ctr, Lab Bioseparat Technol, NIH, 10 Ctr Dr,Bldg 10,Rm 8N230, Bethesda, MD 20892 USA. EM itoy2@mail.nih.gov FU Intramural NIH HHS [Z99 HL999999] NR 7 TC 5 Z9 5 U1 2 U2 9 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0021-9673 EI 1873-3778 J9 J CHROMATOGR A JI J. Chromatogr. A PD DEC 12 PY 2014 VL 1372 BP 128 EP 132 DI 10.1016/j.chroma.2014.09.033 PG 5 WC Biochemical Research Methods; Chemistry, Analytical SC Biochemistry & Molecular Biology; Chemistry GA AX6GK UT WOS:000347020900014 PM 25301393 ER PT J AU Lewis, BA Hanover, JA AF Lewis, Brian A. Hanover, John A. TI O-GlcNAc and the Epigenetic Regulation of Gene Expression SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Review DE Epigenetics; Glycobiology; O-GlcNAcylation; Polycomb; RNA Polymerase II; Signaling; Histones; O-GlcNAc; Transcription ID RNA-POLYMERASE-II; CARBOXYL-TERMINAL DOMAIN; N-ACETYLGLUCOSAMINE TRANSFERASE; TRITHORAX-GROUP PROTEIN; EMBRYONIC STEM-CELLS; HISTONE H3; TETRATRICOPEPTIDE REPEATS; TYROSINE PHOSPHORYLATION; TRANSCRIPTION ELONGATION; MESSENGER-RNA AB O-GlcNAcylation is an abundant nutrient-driven modification linked to cellular signaling and regulation of gene expression. Utilizing precursors derived from metabolic flux, O-GlcNAc functions as a homeostatic regulator. The enzymes of O-GlcNAc cycling, OGT and O-GlcNAcase, act in mitochondria, the cytoplasm, and the nucleus in association with epigenetic writers and erasers of the histone code. Both O-GlcNAc and O-phosphate modify repeats within the RNA polymerase II C-terminal domain (CTD). By communicating with the histone and CTD codes, O-GlcNAc cycling provides a link between cellular metabolic status and the epigenetic machinery. Thus, O-GlcNAcylation is poised to influence trans-generational epigenetic inheritance. C1 [Lewis, Brian A.] NCI, NIH, Bethesda, MD 20892 USA. [Hanover, John A.] NIDDK, NIH, Bethesda, MD 20892 USA. RP Lewis, BA (reprint author), NCI, Lymphoid Malignancies Branch, NIH, Bldg 10,Rm 6B05,10 Ctr Dr, Bethesda, MD 20814 USA. EM lewisbri@mail.nih.gov; jah@helix.nih.gov FU National Institutes of Health from NCI; NIDDK FX This work was supported, in whole or in part, by National Institutes of Health intramural grants from the NCI (to B. A. L.) and NIDDK (to J. A. H.). This is the third article in the Minireview Series on the Thirtieth Anniversary of Research on O-GlcNAcylation of Nuclear and Cytoplasmic Proteins: Nutrient Regulation of Cellular Metabolism and Physiology by O-GlcNAcylation. NR 101 TC 28 Z9 28 U1 7 U2 39 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 EI 1083-351X J9 J BIOL CHEM JI J. Biol. Chem. PD DEC 12 PY 2014 VL 289 IS 50 BP 34440 EP 34448 DI 10.1074/jbc.R114.595439 PG 9 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA AW4OP UT WOS:000346260800004 PM 25336654 ER PT J AU Ke, HJ Sigala, PA Miura, K Morrisey, JM Mather, MW Crowley, JR Henderson, JP Goldberg, DE Long, CA Vaidya, AB AF Ke, Hangjun Sigala, Paul A. Miura, Kazutoyo Morrisey, Joanne M. Mather, Michael W. Crowley, Jan R. Henderson, Jeffrey P. Goldberg, Daniel E. Long, Carole A. Vaidya, Akhil B. TI The Heme Biosynthesis Pathway Is Essential for Plasmodium falciparum Development in Mosquito Stage but Not in Blood Stages SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article DE Heme; Insect; Malaria; Mitochondria; Mitochondrial Metabolism ID COPROPORPHYRINOGEN-III OXIDASE; TANDEM MASS-SPECTROMETRY; MALARIAL PARASITE; METABOLISM; MECHANISM; TARGET; CELLS; DRUG; FERROCHELATASE; PROTEINS AB Background: Malaria parasites require heme for growth. Results: Genetic disruption of the P. falciparum heme biosynthesis pathway ablated growth in mosquitoes but had no effect on blood-stage growth. Conclusion: The heme biosynthesis pathway is only essential for exoerythrocytic parasite growth and transmission to mosquitoes. Significance: Pathway inhibition is unlikely to be an effective antimalarial drug strategy. Heme salvage mechanisms likely exist in blood stages. Heme is an essential cofactor for aerobic organisms. Its redox chemistry is central to a variety of biological functions mediated by hemoproteins. In blood stages, malaria parasites consume most of the hemoglobin inside the infected erythrocytes, forming nontoxic hemozoin crystals from large quantities of heme released during digestion. At the same time, the parasites possess a heme de novo biosynthetic pathway. This pathway in the human malaria parasite Plasmodium falciparum has been considered essential and is proposed as a potential drug target. However, we successfully disrupted the first and last genes of the pathway, individually and in combination. These knock-out parasite lines, lacking 5-aminolevulinic acid synthase and/or ferrochelatase (FC), grew normally in blood-stage culture and exhibited no changes in sensitivity to heme-related antimalarial drugs. We developed a sensitive LC-MS/MS assay to monitor stable isotope incorporation into heme from its precursor 5-[C-13(4)]aminolevulinic acid, and this assay confirmed that de novo heme synthesis was ablated in FC knock-out parasites. Disrupting the FC gene also caused no defects in gametocyte generation or maturation but resulted in a greater than 70% reduction in male gamete formation and completely prevented oocyst formation in female Anopheles stephensi mosquitoes. Our data demonstrate that the heme biosynthesis pathway is not essential for asexual blood-stage growth of P. falciparum parasites but is required for mosquito transmission. Drug inhibition of pathway activity is therefore unlikely to provide successful antimalarial therapy. These data also suggest the existence of a parasite mechanism for scavenging host heme to meet metabolic needs. C1 [Ke, Hangjun; Morrisey, Joanne M.; Mather, Michael W.; Vaidya, Akhil B.] Drexel Univ, Dept Microbiol & Immunol, Ctr Mol Parasitol, Coll Med, Philadelphia, PA 19129 USA. [Sigala, Paul A.; Goldberg, Daniel E.] Washington Univ, Sch Med, Dept Mol Microbiol, St Louis, MO 63110 USA. [Sigala, Paul A.; Goldberg, Daniel E.] Washington Univ, Sch Med, Howard Hughes Med Inst, St Louis, MO 63110 USA. [Miura, Kazutoyo; Long, Carole A.] NIAID, Lab Malaria & Vector Res, NIH, Rockville, MD 20852 USA. [Crowley, Jan R.; Henderson, Jeffrey P.] Washington Univ, Sch Med, Ctr Womens Infect Dis Res, St Louis, MO 63110 USA. [Henderson, Jeffrey P.; Goldberg, Daniel E.] Washington Univ, Sch Med, Dept Med, St Louis, MO 63110 USA. RP Vaidya, AB (reprint author), Drexel Univ, Dept Microbiol & Immunol, Ctr Mol Parasitol, Coll Med, 2900 Queen Lane, Philadelphia, PA 19129 USA. EM avaidya@drexelmed.edu OI Sigala, Paul/0000-0002-3464-3042 FU National Institutes of Health [R01 AI028398, R01 DK099534]; Burroughs Wellcome Fund Career Award at the Scientific Interface; Burroughs Wellcome Fund Career Award for Medical Scientists FX This work was supported, in whole or in part, by National Institutes of Health Grants R01 AI028398 (to A. B. V.) and R01 DK099534 (to J. P. H.).; Recipient of a Burroughs Wellcome Fund Career Award at the Scientific Interface.; Recipient of a Burroughs Wellcome Fund Career Award for Medical Scientists. NR 61 TC 22 Z9 22 U1 4 U2 15 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 EI 1083-351X J9 J BIOL CHEM JI J. Biol. Chem. PD DEC 12 PY 2014 VL 289 IS 50 BP 34827 EP 34837 DI 10.1074/jbc.M114.615831 PG 11 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA AW4OP UT WOS:000346260800034 PM 25352601 ER PT J AU Diepenhorst, NA Petrie, EJ Chen, CZ Wang, A Hossain, MA Bathgate, RAD Gooley, PR AF Diepenhorst, Natalie A. Petrie, Emma J. Chen, Catherine Z. Wang, Amy Hossain, Mohammed Akhter Bathgate, Ross A. D. Gooley, Paul R. TI Investigation of Interactions at the Extracellular Loops of the Relaxin Family Peptide Receptor 1 (RXFP1) SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article DE G Protein-coupled Receptor (GPCR); Nuclear Magnetic Resonance (NMR); Peptide Hormone; Protein Engineering; Receptor Structure-Function; RXFP1; Relaxin; Serelaxin ID CLASS-A MODULE; PROTEIN-COUPLED RECEPTORS; SMALL-MOLECULE AGONISTS; BINDING-SITE; CHEMOKINE-RECEPTOR; CHEMICAL-SYNTHESIS; ACTIVATION; IDENTIFICATION; LGR7; HORMONE AB Background: Extracellular loops of the transmembrane domain of the relaxin receptor RXFP1 are predicted to interact with relaxin. Results: RXFP1 extracellular loops displayed on a scaffold protein enabled investigation of ligand interactions. Conclusion: RXFP1 activation involves interactions between the extracellular loops with relaxin and the receptor LDLa module. Significance: Understanding the molecular mechanisms of RXFP1 activation will aid drug design at this receptor. Relaxin, an emerging pharmaceutical treatment for acute heart failure, activates the relaxin family peptide receptor (RXFP1), which is a class A G-protein-coupled receptor. In addition to the classic transmembrane (TM) domain, RXFP1 possesses a large extracellular domain consisting of 10 leucine-rich repeats and an N-terminal low density lipoprotein class A (LDLa) module. Relaxin-mediated activation of RXFP1 requires multiple coordinated interactions between the ligand and various receptor domains including a high affinity interaction involving the leucine-rich repeats and a predicted lower affinity interaction involving the extracellular loops (ELs). The LDLa is essential for signal activation; therefore the ELs/TM may additionally present an interaction site to facilitate this LDLa-mediated signaling. To overcome the many challenges of investigating relaxin and the LDLa module interactions with the ELs, we engineered the EL1 and EL2 loops onto a soluble protein scaffold, mapping specific ligand and loop interactions using nuclear magnetic resonance spectroscopy. Key EL residues were subsequently mutated in RXFP1, and changes in function and relaxin binding were assessed alongside the RXFP1 agonist ML290 to monitor the functional integrity of the TM domain of these mutant receptors. The outcomes of this work make an important contribution to understanding the mechanism of RXFP1 activation and will aid future development of small molecule RXFP1 agonists/antagonists. C1 [Diepenhorst, Natalie A.; Hossain, Mohammed Akhter; Bathgate, Ross A. D.] Univ Melbourne, Florey Inst Neurosci & Mental Hlth, Parkville, Vic 3010, Australia. [Diepenhorst, Natalie A.; Petrie, Emma J.; Bathgate, Ross A. D.; Gooley, Paul R.] Univ Melbourne, Dept Biochem & Mol Biol, Parkville, Vic 3010, Australia. [Hossain, Mohammed Akhter] Univ Melbourne, Sch Chem, Parkville, Vic 3010, Australia. [Chen, Catherine Z.; Wang, Amy] NIH, Natl Ctr Adv Translat Sci, Div Preclin Innovat, Rockville, MD 20850 USA. RP Bathgate, RAD (reprint author), Univ Melbourne, Florey Inst Neurosci & Mental Hlth, Parkville, Vic 3010, Australia. EM bathgate@florey.edu.au; prg@unimelb.edu.au OI Gooley, Paul/0000-0002-0323-449X; Bathgate, Ross/0000-0001-6301-861X FU National Health and Medical Research Council of Australia [628427, 1043750]; Victorian Government Operational Infrastructure Support Program; State of Victoria; Australian Research Council; Rowden White Foundation; Melbourne Research Fellowship (Career Interruptions); National Health and Medical Research Council Research Fellowship FX This work was supported by National Health and Medical Research Council of Australia Project Grants 628427 and 1043750 (to R. A. D. B. and P. R. G.) by the Victorian Government Operational Infrastructure Support Program, and through instrument funding from the State of Victoria, Australian Research Council, and the Rowden White Foundation.; Recipient of a Melbourne Research Fellowship (Career Interruptions).; Recipient of a National Health and Medical Research Council Research Fellowship. To whom correspondence may be addressed: Florey Inst. of Neuroscience and Mental Health, University of Melbourne, Parkville, Victoria 3010, Australia. Tel.: 61-3-9035-6735; E-mail: bathgate@florey.edu.au. NR 49 TC 7 Z9 7 U1 1 U2 9 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 EI 1083-351X J9 J BIOL CHEM JI J. Biol. Chem. PD DEC 12 PY 2014 VL 289 IS 50 BP 34938 EP 34952 DI 10.1074/jbc.M114.600882 PG 15 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA AW4OP UT WOS:000346260800043 PM 25352603 ER PT J AU Jarvis, ED Mirarab, S Aberer, AJ Li, B Houde, P Li, C Ho, SYW Faircloth, BC Nabholz, B Howard, JT Suh, A Weber, CC da Fonseca, RR Li, JW Zhang, F Li, H Zhou, L Narula, N Liu, L Ganapathy, G Boussau, B Bayzid, MS Zavidovych, V Subramanian, S Gabaldon, T Capella-Gutierrez, S Huerta-Cepas, J Rekepalli, B Munch, K Schierup, M Lindow, B Warren, WC Ray, D Green, RE Bruford, MW Zhan, XJ Dixon, A Li, SB Li, N Huang, YH Derryberry, EP Bertelsen, MF Sheldon, FH Brumfield, RT Mello, CV Lovell, PV Wirthlin, M Schneider, MPC Prosdocimi, F Samaniego, JA Velazquez, AMV Alfaro-Nunez, A Campos, PF Petersen, B Sicheritz-Ponten, T Pas, A Bailey, T Scofield, P Bunce, M Lambert, DM Zhou, Q Perelman, P Driskell, AC Shapiro, B Xiong, ZJ Zeng, YL Liu, SP Li, ZY Liu, BH Wu, K Xiao, J Yinqi, X Zheng, QM Zhang, Y Yang, HM Wang, J Smeds, L Rheindt, FE Braun, M Fjeldsa, J Orlando, L Barker, FK Jonsson, KA Johnson, W Koepfli, KP O'Brien, S Haussler, D Ryder, OA Rahbek, C Willerslev, E Graves, GR Glenn, TC McCormack, J Burt, D Ellegren, H Alstrom, P Edwards, SV Stamatakis, A Mindell, DP Cracraft, J Braun, EL Warnow, T Jun, W Gilbert, MTP Zhang, GJ AF Jarvis, Erich D. Mirarab, Siavash Aberer, Andre J. Li, Bo Houde, Peter Li, Cai Ho, Simon Y. W. Faircloth, Brant C. Nabholz, Benoit Howard, Jason T. Suh, Alexander Weber, Claudia C. da Fonseca, Rute R. Li, Jianwen Zhang, Fang Li, Hui Zhou, Long Narula, Nitish Liu, Liang Ganapathy, Ganesh Boussau, Bastien Bayzid, Md. Shamsuzzoha Zavidovych, Volodymyr Subramanian, Sankar Gabaldon, Toni Capella-Gutierrez, Salvador Huerta-Cepas, Jaime Rekepalli, Bhanu Munch, Kasper Schierup, Mikkel Lindow, Bent Warren, Wesley C. Ray, David Green, Richard E. Bruford, Michael W. Zhan, Xiangjiang Dixon, Andrew Li, Shengbin Li, Ning Huang, Yinhua Derryberry, Elizabeth P. Bertelsen, Mads Frost Sheldon, Frederick H. Brumfield, Robb T. Mello, Claudio V. Lovell, Peter V. Wirthlin, Morgan Cruz Schneider, Maria Paula Prosdocimi, Francisco Samaniego, Jose Alfredo Vargas Velazquez, Amhed Missael Alfaro-Nunez, Alonzo Campos, Paula F. Petersen, Bent Sicheritz-Ponten, Thomas Pas, An Bailey, Tom Scofield, Paul Bunce, Michael Lambert, David M. Zhou, Qi Perelman, Polina Driskell, Amy C. Shapiro, Beth Xiong, Zijun Zeng, Yongli Liu, Shiping Li, Zhenyu Liu, Binghang Wu, Kui Xiao, Jin Yinqi, Xiong Zheng, Qiuemei Zhang, Yong Yang, Huanming Wang, Jian Smeds, Linnea Rheindt, Frank E. Braun, Michael Fjeldsa, Jon Orlando, Ludovic Barker, F. Keith Jonsson, Knud Andreas Johnson, Warren Koepfli, Klaus-Peter O'Brien, Stephen Haussler, David Ryder, Oliver A. Rahbek, Carsten Willerslev, Eske Graves, Gary R. Glenn, Travis C. McCormack, John Burt, Dave Ellegren, Hans Alstrom, Per Edwards, Scott V. Stamatakis, Alexandros Mindell, David P. Cracraft, Joel Braun, Edward L. Warnow, Tandy Jun, Wang Gilbert, M. Thomas P. Zhang, Guojie TI Whole-genome analyses resolve early branches in the tree of life of modern birds SO SCIENCE LA English DT Article ID BIASED GENE CONVERSION; PHYLOGENETIC TREES; SPECIES TREES; SEQUENCE ALIGNMENTS; PARALLEL RADIATIONS; CRETACEOUS ORIGIN; COALESCENT MODEL; MASS EXTINCTION; PASSERINE BIRDS; FOSSIL RECORD AB To better determine the history of modern birds, we performed a genome-scale phylogenetic analysis of 48 species representing all orders of Neoaves using phylogenomic methods created to handle genome-scale data. We recovered a highly resolved tree that confirms previously controversial sister or close relationships. We identified the first divergence in Neoaves, two groups we named Passerea and Columbea, representing independent lineages of diverse and convergently evolved land and water bird species. Among Passerea, we infer the common ancestor of core landbirds to have been an apex predator and confirm independent gains of vocal learning. Among Columbea, we identify pigeons and flamingoes as belonging to sister clades. Even with whole genomes, some of the earliest branches in Neoaves proved challenging to resolve, which was best explained by massive protein-coding sequence convergence and high levels of incomplete lineage sorting that occurred during a rapid radiation after the Cretaceous-Paleogene mass extinction event about 66 million years ago. C1 [Jarvis, Erich D.; Howard, Jason T.; Ganapathy, Ganesh; Zavidovych, Volodymyr] Duke Univ, Med Ctr, Howard Hughes Med Inst, Dept Neurobiol, Durham, NC 27710 USA. [Jarvis, Erich D.; Howard, Jason T.; Ganapathy, Ganesh; Zavidovych, Volodymyr] Duke Univ, Med Ctr, Durham, NC 27710 USA. [Mirarab, Siavash; Bayzid, Md. Shamsuzzoha; Warnow, Tandy] Univ Texas Austin, Dept Comp Sci, Austin, TX 78712 USA. [Aberer, Andre J.; Stamatakis, Alexandros] Heidelberg Inst Theoret Studies, Sci Comp Grp, Heidelberg, Germany. [Li, Bo; Li, Cai; Li, Jianwen; Zhang, Fang; Li, Hui; Zhou, Long; Xiong, Zijun; Zeng, Yongli; Liu, Shiping; Li, Zhenyu; Liu, Binghang; Wu, Kui; Xiao, Jin; Yinqi, Xiong; Zheng, Qiuemei; Zhang, Yong; Zhang, Guojie] BGI Shenzhen, China Natl GeneBank, Shenzhen 518083, Peoples R China. [Li, Bo; Li, Shengbin] Xi An Jiao Tong Univ, Coll Med & Forens, Xian 710061, Peoples R China. [Li, Bo; Li, Cai; da Fonseca, Rute R.; Lindow, Bent; Samaniego, Jose Alfredo; Vargas Velazquez, Amhed Missael; Alfaro-Nunez, Alonzo; Campos, Paula F.; Orlando, Ludovic; Willerslev, Eske; Gilbert, M. Thomas P.] Univ Copenhagen, Nat Hist Museum Denmark, Ctr GeoGenet, DK-1350 Copenhagen, Denmark. [Houde, Peter; Narula, Nitish] New Mexico State Univ, Dept Biol, Las Cruces, NM 88003 USA. [Ho, Simon Y. W.] Univ Sydney, Sch Biol Sci, Sydney, NSW 2006, Australia. [Faircloth, Brant C.] Univ Calif Los Angeles, Dept Ecol & Evolutionary Biol, Los Angeles, CA 90095 USA. [Faircloth, Brant C.] Louisiana State Univ, Dept Biol Sci, Baton Rouge, LA 70803 USA. [Nabholz, Benoit] Univ Montpellier 2, Inst Sci Evolut Montpellier, CNRS, UMR 5554, Montpellier, France. [Suh, Alexander; Weber, Claudia C.; Smeds, Linnea; Ellegren, Hans] Uppsala Univ, Evolutionary Biol Ctr, Dept Evolutionary Biol, SE-75236 Uppsala, Sweden. [Narula, Nitish] Okinawa Inst Sci & Technol Onna Son, Biodivers & Biocomplex Unit, Okinawa 9040495, Japan. [Liu, Liang] Univ Georgia, Dept Stat, Athens, GA 30602 USA. [Liu, Liang] Univ Georgia, Inst Bioinformat, Athens, GA 30602 USA. [Boussau, Bastien] Univ Lyon, Ctr Natl Rech Sci, Lab Biometrie & Biol Evolut, F-69622 Villeurbanne, France. [Subramanian, Sankar; Lambert, David M.] Griffith Univ, Environm Futures Res Inst, Nathan, Qld 4111, Australia. [Gabaldon, Toni; Capella-Gutierrez, Salvador; Huerta-Cepas, Jaime] Ctr Genom Regulat, Bioinformat & Genom Programme, Barcelona 08003, Spain. [Gabaldon, Toni; Capella-Gutierrez, Salvador; Huerta-Cepas, Jaime] Univ Pompeu Fabra, Barcelona, Spain. [Gabaldon, Toni] Inst Catalana Recerca & Estudis Avancats, Barcelona, Spain. [Rekepalli, Bhanu] Univ Tennessee, Oak Ridge Natl Lab, Joint Inst Computat Sci, Oak Ridge, TN 37831 USA. [Munch, Kasper; Schierup, Mikkel] Aarhus Univ, Bioinformat Res Ctr, DK-8000 Aarhus C, Denmark. [Warren, Wesley C.] Washington Univ, Sch Med, Genome Inst, St Louis, MI 63108 USA. [Ray, David] Mississippi State Univ, Dept Biochem Mol Biol Entomol & Plant Pathol, Mississippi State, MS 39762 USA. [Ray, David] Mississippi State Univ, Inst Gen Biocomp & Biotechnol, Mississippi State, MS 39762 USA. [Ray, David] Texas Tech Univ, Dept Biol Sci, Lubbock, TX 79409 USA. [Green, Richard E.; Shapiro, Beth] Univ Calif Santa Cruz, Dept Ecol & Evolutionary Biol, Santa Cruz, CA 95064 USA. [Bruford, Michael W.; Zhan, Xiangjiang] Cardiff Univ, Cardiff Sch Biosci, Organisms & Environm Div, Cardiff CF10 3AX, S Glam, Wales. [Zhan, Xiangjiang] Chinese Acad Sci, Inst Zool, Key Lab Anim Ecol & Conservat Biol, Beijing 100101, Peoples R China. [Dixon, Andrew] Int Wildlife Consultants, Carmarthen SA33 5YL, Dyfed, Wales. [Li, Ning; Huang, Yinhua] China Agr Univ, State Key Lab Agrobiotechnol, Beijing 100094, Peoples R China. [Derryberry, Elizabeth P.] Tulane Univ, Dept Ecol & Evolutionary Biol, New Orleans, LA 70118 USA. [Derryberry, Elizabeth P.; Sheldon, Frederick H.; Brumfield, Robb T.] Louisiana State Univ, Museum Nat Sci, Baton Rouge, LA 70803 USA. [Derryberry, Elizabeth P.; Sheldon, Frederick H.; Brumfield, Robb T.] Louisiana State Univ, Dept Biol Sci, Baton Rouge, LA 70803 USA. [Bertelsen, Mads Frost] Ctr Zoo & Wild Anim Hlth, DK-2000 Frederiksberg, Denmark. [Mello, Claudio V.; Lovell, Peter V.; Wirthlin, Morgan] Oregon Hlth & Sci Univ, Dept Behav Neurosci, Portland, OR 97239 USA. [Mello, Claudio V.; Cruz Schneider, Maria Paula; Prosdocimi, Francisco] Fed Univ Para, Brazilian Avian Genome Consortium CNPq FAPESPA SI, BR-66059 Belem, Para, Brazil. [Cruz Schneider, Maria Paula] Fed Univ Para, Inst Biol Sci, BR-66059 Belem, Para, Brazil. [Prosdocimi, Francisco] Univ Fed Rio de Janeiro, Inst Med Biochem Leopoldo de Meis, BR-21941902 Rio De Janeiro, Brazil. [Petersen, Bent; Sicheritz-Ponten, Thomas] Tech Univ, Dept Syst Biol, Ctr Biol Sequence Anal, DK-2800 Lyngby, Denmark. [Pas, An] Breeding Ctr Endangered Arabian Wildlife, Sharjah, U Arab Emirates. [Bailey, Tom] Dubai Falcon Hosp, Dubai, U Arab Emirates. [Scofield, Paul] Canterbury Museum, Christchurch 8050, New Zealand. [Bunce, Michael; Gilbert, M. Thomas P.] Curtin Univ, Dept Environm & Agr, Trace & Environm DNA Lab, Perth, WA 6102, Australia. [Zhou, Qi] Univ Calif Berkeley, Dept Integrat Biol, Berkeley, CA 94720 USA. [Perelman, Polina] NCI, Lab Genom Div, Frederick, MD 21702 USA. [Perelman, Polina] SB RAS, Inst Mol & Cellular Biol, Novosibirsk, Russia. [Perelman, Polina] Novosibirsk State Univ, Novosibirsk 630090, Russia. [Driskell, Amy C.] Smithsonian Inst, Natl Museum Nat Hist, Washington, DC 20013 USA. [Yang, Huanming; Wang, Jian; Jun, Wang] BGI Shenzhen, Shenzhen 518083, Peoples R China. [Rheindt, Frank E.] Natl Univ Singapore, Dept Biol Sci, Singapore 117548, Singapore. [Braun, Michael] Natl Museum Nat Hist, Dept Vertebrate Zool, Smithsonian Suitland, MD 20746 USA. [Fjeldsa, Jon; Jonsson, Knud Andreas; Rahbek, Carsten; Graves, Gary R.] Univ Copenhagen, Nat Hist Museum Denmark, Ctr Macroecol Evolut & Climate, DK-2100 Copenhagen O, Denmark. [Barker, F. Keith] Univ Minnesota, Bell Museum Nat Hist, St Paul, MN 55108 USA. [Jonsson, Knud Andreas] Nat Hist Museum, Dept Life Sci, London SW7 5BD, England. [Jonsson, Knud Andreas; Rahbek, Carsten] Imperial Coll London, Dept Life Sci, Ascot SL5 7PY, Berks, England. [Johnson, Warren] Smithsonian Conservat Biol Inst, Front Royal, VA 22630 USA. [Koepfli, Klaus-Peter] Smithsonian Conservat Biol Inst, Washington, DC 20008 USA. [O'Brien, Stephen] St Petersburg State Univ, Theodosius Dobzhansky Ctr Genome Bioinformat, St Petersburg 199004, Russia. [O'Brien, Stephen] Nova SE Univ, Oceanog Ctr, Ft Lauderdale, FL 33004 USA. [Haussler, David] Univ Calif Santa Cruz, Ctr Biomol Sci & Engn, Santa Cruz, CA 95064 USA. [Ryder, Oliver A.] San Diego Zoo Inst Conservat Res, Escondido, CA 92027 USA. [Graves, Gary R.] Smithsonian Inst, Dept Vertebrate Zool, Natl Museum Nat Hist, MRC 116, Washington, DC 20013 USA. [Glenn, Travis C.] Univ Georgia, Dept Environm Hlth Sci, Athens, GA 30602 USA. [McCormack, John] Occidental Coll, Moore Lab Zool, Los Angeles, CA 90041 USA. [McCormack, John] Occidental Coll, Dept Biol, Los Angeles, CA 90041 USA. [Burt, Dave] Univ Edinburgh, Roslin Inst, Dept Genom & Genet, Roslin EH25 9RG, Midlothian, Scotland. [Burt, Dave] Univ Edinburgh, Royal Dick Sch Vet Studies, Roslin EH25 9RG, Midlothian, Scotland. [Alstrom, Per] Swedish Univ Agr Sci, Swedish Species Informat Ctr, SE-75007 Uppsala, Sweden. [Alstrom, Per] Chinese Acad Sci, Inst Zool, Key Lab Zool Syst & Evolut, Beijing 100101, Peoples R China. [Edwards, Scott V.] Harvard Univ, Dept Organism & Evolutionary Biol, Cambridge, MA 02138 USA. [Edwards, Scott V.] Harvard Univ, Museum Comparat Zool, Cambridge, MA 02138 USA. [Stamatakis, Alexandros] Karlsruhe Inst Technol, Inst Theoret Informat, Dept Informat, D-76131 Karlsruhe, Germany. [Mindell, David P.] Univ Calif San Francisco, Dept Biochem & Biophys, San Francisco, CA 94158 USA. [Cracraft, Joel] Amer Museum Nat Hist, Dept Ornithol, New York, NY 10024 USA. [Braun, Edward L.] Univ Florida, Dept Biol, Gainesville, FL 32611 USA. [Braun, Edward L.] Univ Florida, Genet Inst, Gainesville, FL 32611 USA. [Warnow, Tandy] Univ Illinois, Dept Bioengn, Urbana, IL 61801 USA. [Warnow, Tandy] Univ Illinois, Dept Comp Sci, Urbana, IL 61801 USA. [Jun, Wang] Univ Copenhagen, Dept Biol, DK-2200 Copenhagen, Denmark. [Jun, Wang] King Abdulaziz Univ, Princess Al Jawhara Ctr Excellence Res Hereditary, Jeddah 21589, Saudi Arabia. [Jun, Wang] Macau Univ Sci & Technol, Taipa 999078, Macau, Peoples R China. [Jun, Wang] Univ Hong Kong, Dept Med, Hong Kong, Hong Kong, Peoples R China. [Zhang, Guojie] Univ Copenhagen, Dept Biol, Ctr Social Evolut, DK-2100 Copenhagen, Denmark. RP Jarvis, ED (reprint author), Duke Univ, Med Ctr, Howard Hughes Med Inst, Dept Neurobiol, Durham, NC 27710 USA. EM jarvis@neuro.duke.edu; tandywarnow@gmail.com; wangj@genomics.cn; mtpgilbert@gmail.com; zhanggj@genomics.cn RI Wang, Jun/B-9503-2016; Ho, Simon/A-8417-2008; Gabaldon, Toni/A-7336-2008; Samaniego Castruita, Jose Alfredo/B-9033-2015; Zhang, Guojie/B-6188-2014; Alstrom, Per/C-1619-2015; Gilbert, Marcus/A-8936-2013; Campos, Paula/B-1634-2010; Rahbek, Carsten/L-1129-2013; Fjeldsa, Jon/A-9699-2013; Munch, Kasper/A-1434-2010; Capella-Gutierrez, Salvador/H-5053-2015; Brumfield, Robb/K-6108-2015; Orlando, Ludovic/A-8932-2013; Perelman, Polina/N-8088-2015; Bruford, Michael/D-3750-2009; da Fonseca, Rute/F-9143-2013; Wang, Jun/C-8434-2016; Jarvis, Erich/A-2319-2008; Schierup, Mikkel/F-1675-2010; Prosdocimi, Francisco/F-6847-2012; Stamatakis, Alexandros/B-8740-2009; publist, CMEC/C-3010-2012; Narula, Nitish/G-5784-2015; publicationpage, cmec/B-4405-2017; OI Li, Cai/0000-0001-7843-2151; Wirthlin, Morgan/0000-0001-7967-7070; Wang, Jun/0000-0002-2113-5874; Alfaro-Nunez, Alonzo/0000-0002-4050-5041; Weber, Claudia/0000-0002-5910-8898; Edwards, Scott/0000-0003-2535-6217; Ho, Simon/0000-0002-0361-2307; Gabaldon, Toni/0000-0003-0019-1735; Samaniego Castruita, Jose Alfredo/0000-0001-5904-1198; Zhang, Guojie/0000-0001-6860-1521; Alstrom, Per/0000-0001-7182-2763; Gilbert, Marcus/0000-0002-5805-7195; Campos, Paula/0000-0003-1285-4671; Fjeldsa, Jon/0000-0003-0790-3600; Munch, Kasper/0000-0003-2880-6252; Capella-Gutierrez, Salvador/0000-0002-0309-604X; Brumfield, Robb/0000-0003-2307-0688; Orlando, Ludovic/0000-0003-3936-1850; Perelman, Polina/0000-0002-0982-5100; Bruford, Michael/0000-0001-6357-6080; da Fonseca, Rute/0000-0002-2805-4698; Wang, Jun/0000-0002-8540-8931; Jarvis, Erich/0000-0001-8931-5049; Schierup, Mikkel/0000-0002-5028-1790; Prosdocimi, Francisco/0000-0002-6761-3069; Narula, Nitish/0000-0002-8309-8642; Bertelsen, Mads/0000-0001-9201-7499; Suh, Alexander/0000-0002-8979-9992; Faircloth, Brant/0000-0002-1943-0217; Braun, Edward/0000-0003-1643-5212; Howard, Jason/0000-0003-3265-5127; Subramanian, Sankar/0000-0002-2375-3254; Shapiro, Beth/0000-0002-2733-7776; Scofield, Richard/0000-0002-7510-6980; Jonsson, Knud/0000-0002-1875-9504 FU BGI; NIH [DP1OD000448]; HHMI; Marie Curie International Incoming Fellowship [300837]; NSF [DEB 0733029, DBI 1062335]; NSF IR/D program; Danish National Research Foundation [DNRF94]; Lundbeck Foundation [R52-A5062] FX Genome assemblies, annotations, alignments, tree files, and other data sets used or generated in this study are available at GigaScience, the National Center for Biotechnology Information (NCBI), ENSEMBL, CoGe, UCSC, and other sources listed in SM13 (table S17). We thank S. Edmunds at GigaScience, K. Pruit at NCBI, and P. Flicek at ENSEMBL for making this possible. The majority of genome sequencing and annotation was supported by internal funding from BGI. Additional major support is from the coordinators of the project: E.D.J. from the HHMI and NIH Directors Pioneer Award DP1OD000448; S.M. from an HHMI International Student Fellowship; G.Z. from Marie Curie International Incoming Fellowship grant (300837); T.W. from NSF DEB 0733029, NSF DBI 1062335, and NSF IR/D program; and M.T.P.G. from a Danish National Research Foundation grant (DNRF94) and a Lundbeck Foundation grant (R52-A5062). J. Fjeldsa generated the bird drawings used in the figures. O.A.R. acknowledges a uniform biological material transfer agreement between San Diego Zoo Global and BGI used for some tissue samples. R.E.G. declares that he is President of Dovetail Genomics, with no conflicts of interest. Additional acknowledgements are listed in the supplementary materials. We thank the following for allowing us to conduct the computationally intensive analyses for this study: Heidelberg Institute for Theoretical Studies; San Diego Supercomputer Center, with support by an NSF grant; SuperMUC Petascale System at the Leibniz Supercomputing Center; Technical University of Denmark; Texas Advanced Computing Center; Georgia Advanced Computing Resource Center, a partnership between the University of Georgia's Office of the Vice President for Research and Office of the Vice President for Information Technology; Amazon Web Services; BGI; the Nautilus supercomputer at the National Institute for Computational Sciences of the University of Tennessee and Smithsonian; and Duke University Institute for Genome Sciences and Policy. NR 101 TC 306 Z9 311 U1 46 U2 353 PU AMER ASSOC ADVANCEMENT SCIENCE PI WASHINGTON PA 1200 NEW YORK AVE, NW, WASHINGTON, DC 20005 USA SN 0036-8075 EI 1095-9203 J9 SCIENCE JI Science PD DEC 12 PY 2014 VL 346 IS 6215 BP 1320 EP 1331 DI 10.1126/science.1253451 PG 12 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA AW3MA UT WOS:000346189600036 PM 25504713 ER PT J AU Xu, X Zhou, ZH Dudley, R Mackem, S Chuong, CM Erickson, GM Varricchio, DJ AF Xu, Xing Zhou, Zhonghe Dudley, Robert Mackem, Susan Chuong, Cheng-Ming Erickson, Gregory M. Varricchio, David J. TI An integrative approach to understanding bird origins SO SCIENCE LA English DT Review ID DINOSAUR TROODON-FORMOSUS; NON-AVIAN DINOSAURS; THEROPOD DINOSAURS; FEATHERED DINOSAURS; EVOLUTIONARY ORIGIN; REPRODUCTIVE TRAITS; PROTEIN SEQUENCES; GROWTH-PATTERNS; SKIN APPENDAGES; DERMAL PAPILLAE AB Recent discoveries of spectacular dinosaur fossils overwhelmingly support the hypothesis that birds are descended from maniraptoran theropod dinosaurs, and furthermore, demonstrate that distinctive bird characteristics such as feathers, flight, endothermic physiology, unique strategies for reproduction and growth, and a novel pulmonary system originated among Mesozoic terrestrial dinosaurs. The transition from ground-living to flight-capable theropod dinosaurs now probably represents one of the best-documented major evolutionary transitions in life history. Recent studies in developmental biology and other disciplines provide additional insights into how bird characteristics originated and evolved. The iconic features of extant birds for the most part evolved in a gradual and stepwise fashion throughout archosaur evolution. However, new data also highlight occasional bursts of morphological novelty at certain stages particularly close to the origin of birds and an unavoidable complex, mosaic evolutionary distribution of major bird characteristics on the theropod tree. Research into bird origins provides a premier example of how paleontological and neontological data can interact to reveal the complexity of major innovations, to answer key evolutionary questions, and to lead to new research directions. A better understanding of bird origins requires multifaceted and integrative approaches, yet fossils necessarily provide the final test of any evolutionary model. C1 [Xu, Xing; Zhou, Zhonghe] Chinese Acad Sci, Inst Vertebrate Paleontol & Paleoanthropol, Key Lab Vertebrate Evolut & Human Origins, Beijing 100044, Peoples R China. [Dudley, Robert] Univ Calif Berkeley, Dept Integrat Biol, Berkeley, CA 94720 USA. [Mackem, Susan] NCI Frederick, Canc & Dev Biol Lab, Ctr Canc Res, NIH, Frederick, MD 21702 USA. [Chuong, Cheng-Ming] Univ So Calif, Dept Pathol, Los Angeles, CA 90033 USA. [Erickson, Gregory M.] Florida State Univ, Dept Biol Sci, Tallahassee, FL 32306 USA. [Varricchio, David J.] Montana State Univ, Bozeman, MT 59717 USA. [Chuong, Cheng-Ming] Cheng Kung Univ, Lab Wound Repair & Regenerat, Grad Inst Clin Med, Tainan 70101, Taiwan. RP Xu, X (reprint author), Chinese Acad Sci, Inst Vertebrate Paleontol & Paleoanthropol, Key Lab Vertebrate Evolut & Human Origins, Beijing 100044, Peoples R China. EM xu.xing@ivpp.ac.cn FU Fukui Prefecture Dinosaur Museum; National Natural Science Foundation of China [41120124002]; 973 program [2012CB821900]; U.S. National Institute of Arthritis and Musculoskeletal Diseases, NIH [AR 60306, 47364]; NSF [DBI 0446224, EAR 044186549, EAR 0847777] FX We thank Y. Liu, L. Xing, R. Li, X. Ding, P. M. O'Connor, M. Ellison, H. Zang, and K. Womble for illustrations. X. X. and Z.H.Z. thank X. Zheng (Shandong Tianyu Museum of Nature) and H. Li (Jizantang Museum) for access to specimens in their care. D.J.V. thanks the Fukui Prefecture Dinosaur Museum for research support. X. X. and Z.H.Z. are supported by the National Natural Science Foundation of China (41120124002) and 973 program (2012CB821900), C.M.C. by U.S. National Institute of Arthritis and Musculoskeletal Diseases, NIH, grant AR 60306 and 47364, G.M.E. by NSF grants DBI 0446224 and EAR 044186549, and D.J.V. by NSF grant EAR 0847777. NR 150 TC 39 Z9 41 U1 15 U2 274 PU AMER ASSOC ADVANCEMENT SCIENCE PI WASHINGTON PA 1200 NEW YORK AVE, NW, WASHINGTON, DC 20005 USA SN 0036-8075 EI 1095-9203 J9 SCIENCE JI Science PD DEC 12 PY 2014 VL 346 IS 6215 BP 1341 EP + AR 1253293 DI 10.1126/science.1253293 PG 11 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA AW3MA UT WOS:000346189600043 PM 25504729 ER PT J AU Morales, M Root, DH AF Morales, M. Root, D. H. TI GLUTAMATE NEURONS WITHIN THE MIDBRAIN DOPAMINE REGIONS SO NEUROSCIENCE LA English DT Review DE ventral tegmental area; substantia nigra; retrorubral field; dopamine; VGluT2; Addiction ID VENTRAL TEGMENTAL AREA; NUCLEUS-ACCUMBENS DOPAMINE; FLUORESCENT RETROGRADE TRACER; SUBSTANTIA-NIGRA; RAT-BRAIN; ELECTROPHYSIOLOGICAL PROPERTIES; RETRORUBRAL FIELD; REWARD-SEEKING; FRONTAL-CORTEX; IN-VITRO AB Midbrain dopamine systems play important roles in Parkinson's disease, schizophrenia, addiction, and depression. The participation of midbrain dopamine systems in diverse clinical contexts suggests these systems are highly complex. Midbrain dopamine regions contain at least three neuronal phenotypes: dopaminergic, GABAergic, and glutamatergic. Here, we review the locations, subtypes, and functions of glutamatergic neurons within midbrain dopamine regions. Vesicular glutamate transporter 2 (VGluT2) mRNA-expressing neurons are observed within each midbrain dopamine system. Within rat retrorubral field (RRF), large populations of VGluT2 neurons are observed throughout its anteroposterior extent. Within rat substantia nigra pars compacta (SNC), VGluT2 neurons are observed centrally and caudally, and are most dense within the laterodorsal subdivision. RRF and SNC rat VGluT2 neurons lack tyrosine hydroxylase (TH), making them an entirely distinct population of neurons from dopaminergic neurons. The rat ventral tegmental area (VTA) contains the most heterogeneous populations of VGluT2 neurons. VGluT2 neurons are found in each VTA subnucleus but are most dense within the anterior midline subnuclei. Some subpopulations of rat VGluT2 neurons co-express TH or glutamic acid decarboxylase (GAD), but most of the VGluT2 neurons lack TH or GAD. Different subsets of rat VGluT2-TH neurons exist based on the presence or absence of vesicular monoamine transporter 2, dopamine transporter, or D2 dopamine receptor. Thus, the capacity by which VGluT2-TH neurons may release dopamine will differ based on their capacity to accumulate vesicular dopamine, uptake extracellular dopamine, or be autoregulated by dopamine. Rat VTA VGluT2 neurons exhibit intrinsic VTA projections and extrinsic projections to the accumbens and to the prefrontal cortex. Mouse VTA VGluT2 neurons project to accumbens shell, prefrontal cortex, ventral pallidum, amygdala, and lateral habenula. Given their molecular diversity and participation in circuits involved in addiction, we hypothesize that individual VGluT2 subpopulations of neurons play unique roles in addiction and other disorders. This article is part of a Special Issue entitled: Ventral Tegmentum & Dopamine. Published by Elsevier Ltd. on behalf of IBRO. C1 [Morales, M.; Root, D. H.] NIDA, Neuronal Networks Sect, Integrat Neurosci Res Branch, Baltimore, MD 21224 USA. RP Morales, M (reprint author), NIDA, Neuronal Networks Sect, Integrat Neurosci Res Branch, 251 Bayview Blvd,Suite 200, Baltimore, MD 21224 USA. EM mmorales@intra.nida.nih.gov FU NIDA Intramural Research Program FX This research was supported by the NIDA Intramural Research Program. NR 77 TC 64 Z9 65 U1 4 U2 32 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0306-4522 EI 1873-7544 J9 NEUROSCIENCE JI Neuroscience PD DEC 12 PY 2014 VL 282 BP 60 EP 68 DI 10.1016/j.neuroscience.2014.05.032 PG 9 WC Neurosciences SC Neurosciences & Neurology GA AU3KS UT WOS:000345512600005 PM 24875175 ER PT J AU Hong, S Hikosaka, O AF Hong, S. Hikosaka, O. TI PEDUNCULOPONTINE TEGMENTAL NUCLEUS NEURONS PROVIDE REWARD, SENSORIMOTOR, AND ALERTING SIGNALS TO MIDBRAIN DOPAMINE NEURONS SO NEUROSCIENCE LA English DT Review DE antidromic activation; reward value; salience; cuneiform nucleus; substantia nigra pars compacta; monkey ID SUBSTANTIA-NIGRA NEURONS; LATERAL HABENULA; PARKINSONS-DISEASE; BASAL GANGLIA; SQUIRREL-MONKEY; MESOPONTINE TEGMENTUM; MOTIVATIONAL SIGNALS; GABAERGIC NEURONS; GLOBUS-PALLIDUS; BRAIN-TISSUE AB Dopamine (DA) neurons in the midbrain are crucial for motivational control of behavior. However, recent studies suggest that signals transmitted by DA neurons are heterogeneous. This may reflect a wide range of inputs to DA neurons, but which signals are provided by which brain areas is still unclear. Here we focused on the pedunculopontine tegmental nucleus (PPTg) in macaque monkeys and characterized its inputs to DA neurons. Since the PPTg projects to many brain areas, it is crucial to identify PPTg neurons that project to DA neuron areas. For this purpose we used antidromic activation technique by electrically stimulating three locations (medial, central, lateral) in the substantia nigra pars compacta (SNc). We found SNc-projecting neurons mainly in the PPTg, and some in the cuneiform nucleus. Electrical stimulation in the SNc-projecting PPTg regions induced a burst of spikes in presumed DA neurons, suggesting that the PPTg-DA (SNc) connection is excitatory. Behavioral tasks and clinical tests showed that the SNc-projecting PPTg neurons encoded reward, sensorimotor and arousal/alerting signals. Importantly, reward-related PPTg neurons tended to project to the medial and central SNc, whereas sensorimotor/arousal/alerting-related PPTg neurons tended to project to the lateral SNc. Most reward-related signals were positively biased: excitation and inhibition when a better and worse reward was expected, respectively. These PPTg neurons tended to retain the reward value signal until after a reward outcome, representing 'value state'; this was different from DA neurons which show phasic signals representing 'value change'. Our data, together with previous studies, suggest that PPTg neurons send positive reward-related signals mainly to the medial-central SNc where DA neurons encode motivational values, and sensorimotor/arousal signals to the lateral SNc where DA neurons encode motivational salience. This article is part of a Special Issue entitled: Ventral Tegmentum & Dopamine. Published by Elsevier Ltd. on behalf of IBRO. C1 [Hong, S.] MIT, McGovern Inst Brain Res, Cambridge, MA 02139 USA. [Hong, S.] MIT, Dept Brain & Cognit Sci, Cambridge, MA 02139 USA. [Hong, S.; Hikosaka, O.] NEI, Sensorimotor Res Lab, NIH, Bethesda, MD 20892 USA. RP Hikosaka, O (reprint author), NEI, Sensorimotor Res Lab, NIH, 49 Convent Dr, Bethesda, MD 20892 USA. EM oh@lsr.nei.nih.gov FU Intramural Research Program at the National Institutes of Health, National Eye Institute FX We thank M. Yasuda, I. Monosov, and E. Bromberg-Martin for discussions and M. Smith, D. Parker, I. Bunea, M. K. Smith, G. Tansey, A. M. Nichols, T. W. Ruffner, J.W. McClurkin, and A. V. Hays for technical assistance. This research was supported by the Intramural Research Program at the National Institutes of Health, National Eye Institute. NR 69 TC 27 Z9 27 U1 1 U2 8 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0306-4522 EI 1873-7544 J9 NEUROSCIENCE JI Neuroscience PD DEC 12 PY 2014 VL 282 BP 139 EP 155 DI 10.1016/j.neuroscience.2014.07.002 PG 17 WC Neurosciences SC Neurosciences & Neurology GA AU3KS UT WOS:000345512600011 PM 25058502 ER PT J AU Deniger, DC Moyes, JS Cooper, LJN AF Deniger, Drew C. Moyes, Judy S. Cooper, Laurence J. N. TI Clinical applications of gamma delta T cells with multivalent immunity SO FRONTIERS IN IMMUNOLOGY LA English DT Review DE cancer; immunotherapy; gamma delta T cells; adoptive T-cell therapy; T-cell receptor; allogeneic transplantation; chimeric antigen receptors; artificial APC ID CHIMERIC ANTIGEN RECEPTOR; SLEEPING-BEAUTY TRANSPOSONS; ADOPTIVE IMMUNOTHERAPY; CANCER-IMMUNOTHERAPY; EX-VIVO; PRESENTING CELLS; GENE-THERAPY; IN-VITRO; BROMOHYDRIN PYROPHOSPHATE; LYMPHOID MALIGNANCIES AB gamma delta T cells hold promise for adoptive immunotherapy because of their reactivity to bacteria, viruses, and tumors. However, these cells represent a small fraction (1-5%) of the peripheral T-cell pool and require activation and propagation to achieve clinical benefit. Aminobisphosphonates specifically expand the V gamma 9V delta 2 subset of gamma delta T cells and have been used in clinical trials of cancer where objective responses were detected. The V gamma 9V delta 2 T cell receptor (TCR) heterodimer binds multiple ligands and results in a multivalent attack by a monoclonal T cell population. Alternatively, populations of gamma delta T cells with oligoclonal or polyclonal TCR repertoire could be infused for broad-range specificity. However, this goal has been restricted by a lack of applicable expansion protocols for non-V gamma 9V delta 2 cells. Recent advances using immobilized antigens, agonistic monoclonal antibodies (mAbs), tumor-derived artificial antigen presenting cells (aAPC), or combinations of activating mAbs and aAPC have been successful in expanding gamma delta T cells with oligoclonal or polyclonal TCR repertoires. Immobilized major histocompatibility complex Class-I chain-related A was a stimulus for gamma delta T cells expressing TCR delta 1 isotypes, and plate-bound activating antibodies have expanded V delta 1 and V delta 2 cells ex vivo. Clinically sufficient quantities of TCR delta 1, TCR delta 2, and TCR gamma 1(neg)TCR delta 2(neg) have been produced following co-culture on aAPC, and these subsets displayed differences in memory phenotype and reactivity to tumors in vitro and in vivo. Gamma delta T cells are also amenable to genetic modification as evidenced by introduction of alpha beta TCRs, chimeric antigen receptors, and drug-resistance genes. This represents a promising future for the clinical application of oligoclonal or polyclonal gamma delta T cells in autologous and allogeneic settings that builds on current trials testing the safety and efficacy of V gamma 9V delta 2 T cells. C1 [Deniger, Drew C.] NCI, Surg Branch, Bethesda, MD 20892 USA. [Moyes, Judy S.; Cooper, Laurence J. N.] Univ Texas MD Anderson Canc Ctr, Div Pediat, Houston, TX 77030 USA. [Cooper, Laurence J. N.] Univ Texas Houston, Grad Sch Biomed Sci, UT MD Anderson Canc Ctr, Houston, TX USA. RP Cooper, LJN (reprint author), Univ Texas MD Anderson Canc Ctr, Div Pediat, Unit 907, 1515 Holcombe Blvd, Houston, TX 77030 USA. EM ljncooper@mdanderson.org FU Cancer Center Core Grant [CA16672]; RO1 [CA124782, CA120956, CA141303]; P01 [CA148600]; SPORE [CA83639]; Albert J. Ward Foundation; Alex Lemonade Stand Foundation; American Legion Auxiliary, Burroughs Wellcome Fund; Cancer Answers; Cancer Prevention and Research Institute of Texas; Charles B. Goddard Foundation of Texas; CLL Global Research Foundation; DARPA (Defense Sciences Office); Department of Defense; Estate of Noelan L. Bibler; Gillson Longenbaugh Foundation; Harry T. Mangurian, Jr., Fund for Leukemia Immunotherapy; Khalifa Bin Zayed Al Nahyan Foundation; Leukemia and Lymphoma Society; Lymphoma Research Foundation; Miller Foundation; Moon Shot program at MDACC, Mr. Herb Simons; Mr. and Mrs. Joe H. Scales; Mr. Thomas Scott; National Foundation for Cancer Research; Pediatric Cancer Research Foundation; Sheikh Khalifa Bin Zayed Al Nahyan Institute for Personalized Cancer Therapy; R. W. Butcher Foundation, University of Texas MD Anderson Cancer Center Sister Institution Network Fund; Moon Shot Fund; William Lawrence and Blanche Hughes Children's Foundation FX Funding for this work was provided by Cancer Center Core Grant (CA16672); RO1 (CA124782, CA120956, CA141303; CA141303); P01 (CA148600); SPORE (CA83639); Albert J. Ward Foundation; Alex Lemonade Stand Foundation; American Legion Auxiliary, Burroughs Wellcome Fund; Cancer Answers; Cancer Prevention and Research Institute of Texas; Charles B. Goddard Foundation of Texas; CLL Global Research Foundation; DARPA (Defense Sciences Office); Department of Defense; Estate of Noelan L. Bibler; Gillson Longenbaugh Foundation; Harry T. Mangurian, Jr., Fund for Leukemia Immunotherapy; Khalifa Bin Zayed Al Nahyan Foundation; Leukemia and Lymphoma Society; Lymphoma Research Foundation; Miller Foundation; Moon Shot program at MDACC, Mr. Herb Simons; Mr. and Mrs. Joe H. Scales; Mr. Thomas Scott; National Foundation for Cancer Research; Pediatric Cancer Research Foundation; Sheikh Khalifa Bin Zayed Al Nahyan Institute for Personalized Cancer Therapy; R. W. Butcher Foundation, University of Texas MD Anderson Cancer Center Sister Institution Network Fund and Moon Shot Fund; William Lawrence and Blanche Hughes Children's Foundation. NR 116 TC 14 Z9 15 U1 2 U2 10 PU FRONTIERS RESEARCH FOUNDATION PI LAUSANNE PA PO BOX 110, LAUSANNE, 1015, SWITZERLAND SN 1664-3224 J9 FRONT IMMUNOL JI Front. Immunol. PD DEC 11 PY 2014 VL 5 AR 636 DI 10.3389/fimmu.2014.00636 PG 10 WC Immunology SC Immunology GA CI1WJ UT WOS:000354535500001 PM 25566249 ER PT J AU Lin, FC Karwan, M Saleh, B Hodge, DL Chan, T Boelte, KC Keller, JR Young, HA AF Lin, Fan-ching Karwan, Megan Saleh, Bahara Hodge, Deborah L. Chan, Tim Boelte, Kimberly C. Keller, Jonathan R. Young, Howard A. TI IFN-gamma causes aplastic anemia by altering hematopoietic stem/progenitor cell composition and disrupting lineage differentiation SO BLOOD LA English DT Article ID PAROXYSMAL-NOCTURNAL HEMOGLOBINURIA; NECROSIS-FACTOR-ALPHA; BONE-MARROW PLASMA; INTERFERON-GAMMA; T-CELLS; IMMUNOSUPPRESSIVE THERAPY; IMMUNE-RESPONSES; STEM-CELLS; ERYTHROPOIESIS; MICE AB Aplastic anemia (AA) is characterized by hypocellular marrow and peripheral pancytopenia. Because interferon gamma (IFN-gamma) can be detected in peripheral blood mononuclear cells of AA patients, it has been hypothesized that autoreactive T lymphocytes may be involved in destroying the hematopoietic stem cells. We have observed AA-like symptoms in our IFN-gamma adenylate-uridylate-rich element (ARE)-deleted (del) mice, which constitutively express a low level of IFN-gamma under normal physiologic conditions. Because no T-cell autoimmunity was observed, we hypothesized that IFN-gamma may be directly involved in the pathophysiology of AA. In these mice, we did not detect infiltration of T cells in bone marrow (BM), and the existing T cells seemed to be hyporesponsive. We observed inhibition in myeloid progenitor differentiation despite an increase in serum levels of cytokines involved in hematopoietic differentiation and maturation. Furthermore, there was a disruption in erythropoiesis and B-cell differentiation. The same phenomena were also observed in wild-type recipients of IFN-gamma ARE-del BM. The data suggest that AA occurs when IFN-gamma inhibits the generation of myeloid progenitors and prevents lineage differentiation, as opposed to infiltration of activated T cells. These results may be useful in improving treatment as well as maintaining a disease-free status. C1 [Lin, Fan-ching; Saleh, Bahara; Hodge, Deborah L.; Chan, Tim; Boelte, Kimberly C.; Young, Howard A.] NCI, Canc & Inflammat Program, Ctr Canc Res, Frederick, MD 21701 USA. [Karwan, Megan] Leidos Biomed Res Inc, Lab Anim Sci, Frederick Natl Lab Canc Res, Frederick, MD USA. [Keller, Jonathan R.] NCI, Hematopoiesis & Stem Cell Biol Sect, Ctr Canc Res, Frederick, MD 21701 USA. RP Lin, FC (reprint author), Canc & Inflammat Program, POB B,Bldg 560,Room 31-16, Frederick, MD 21702 USA. EM fanching.lin@nih.gov; kellerjo@mail.nih.gov; younghow@mail.nih.gov FU National Cancer Institute; National Institutes of Health [Z1A BC009283-30] FX This work is supported by National Cancer Institute intramural funding and National Institutes of Health grant Z1A BC009283-30. NR 32 TC 13 Z9 15 U1 1 U2 13 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 2021 L ST NW, SUITE 900, WASHINGTON, DC 20036 USA SN 0006-4971 EI 1528-0020 J9 BLOOD JI Blood PD DEC 11 PY 2014 VL 124 IS 25 BP 3699 EP 3708 DI 10.1182/blood-2014-01-549527 PG 10 WC Hematology SC Hematology GA AY3EM UT WOS:000347467400007 PM 25342713 ER PT J AU Burgess, RC Burman, B Kruhlak, MJ Misteli, T AF Burgess, Rebecca C. Burman, Bharat Kruhlak, Michael J. Misteli, Tom TI Activation of DNA Damage Response Signaling by Condensed Chromatin SO CELL REPORTS LA English DT Article ID DOUBLE-STRAND BREAKS; REMODELING FACTOR CHD4; MAMMALIAN-CELLS; ATM ACTIVATION; HISTONE H2AX; IN-VIVO; HETEROCHROMATIN PROTEIN-1; KAP-1 PHOSPHORYLATION; REPAIR; GENOME AB The DNA damage response (DDR) occurs in the context of chromatin, and architectural features of chromatin have been implicated in DNA damage signaling and repair. Whereas a role of chromatin decondensation in the DDR is well established, we show here that chromatin condensation is integral to DDR signaling. We find that, in response to DNA damage chromatin regions transiently expand before undergoing extensive compaction. Using a protein-chromatin- tethering system to create defined chromatin domains, we show that interference with chromatin condensation results in failure to fully activate DDR. Conversely, forced induction of local chromatin condensation promotes ataxia telangiectasia mutated (ATM)-and ATR-dependent activation of upstream DDR signaling in a break-independent manner. Whereas persistent chromatin compaction enhanced upstream DDR signaling from irradiation-induced breaks, it reduced recovery and survival after damage. Our results demonstrate that chromatin condensation is sufficient for activation of DDR signaling and is an integral part of physiological DDR signaling. C1 [Burgess, Rebecca C.; Burman, Bharat; Misteli, Tom] NCI, NIH, Bethesda, MD 20892 USA. [Burman, Bharat] Tufts Univ, Sackler Sch Biomed Sci, Program Cell Mol & Dev Biol, Boston, MA 02111 USA. [Kruhlak, Michael J.] NCI, Expt Immunol Branch, NIH, Bethesda, MD 20892 USA. RP Misteli, T (reprint author), NCI, NIH, Bethesda, MD 20892 USA. EM mistelit@mail.nih.gov FU Intramural Research Program of the NIH, NCI, Center for Cancer Research FX The authors thank Andrew Belmont, Daniel Foltz, Alexander Tarakhovsky, Evi Soutoglou, Maria Jasin, David Skalnik, and Thomas Jenuwein for reagents. Members of the T.M. lab, particularly Vassilis Roukos, provided technical support and comments. Imaging was performed in the NCI Fluorescence Imaging facility, and FACS was performed in the NCI Vaccine Branch FACS Core Facility. This work was supported by the Intramural Research Program of the NIH, NCI, Center for Cancer Research. NR 83 TC 36 Z9 36 U1 1 U2 23 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 2211-1247 J9 CELL REP JI Cell Reports PD DEC 11 PY 2014 VL 9 IS 5 BP 1703 EP 1717 DI 10.1016/j.celrep.2014.10.060 PG 15 WC Cell Biology SC Cell Biology GA AX3PR UT WOS:000346851900016 PM 25464843 ER PT J AU Muppidi, JR Schmitz, R Green, JA Xiao, WM Larsens, AB Braun, SE An, JP Xu, Y Rosenwald, A Ott, G Gascoyne, RD Rimsza, LM Campo, E Jaffe, ES Delabie, J Smeland, EB Braziel, RM Tubbs, RR Cook, JR Weisenburger, DD Chan, WC Vaidehi, N Staudt, LM Cyster, JG AF Muppidi, Jagan R. Schmitz, Roland Green, Jesse A. Xiao, Wenming Larsens, Adrien B. Braun, Sterling E. An, Jinping Xu, Ying Rosenwald, Andreas Ott, German Gascoyne, Randy D. Rimsza, Lisa M. Campo, Elias Jaffe, Elaine S. Delabie, Jan Smeland, Erlend B. Braziel, Rita M. Tubbs, Raymond R. Cook, J. R. Weisenburger, Dennis D. Chan, Wing C. Vaidehi, Nagarajan Staudt, Louis M. Cyster, Jason G. TI Loss of signalling via G alpha 13 in germinal centre B-cell-derived lymphoma SO NATURE LA English DT Article ID SOMATIC MUTATIONS; BURKITT-LYMPHOMA; PATHOGENESIS; DISEASE; EZH2; EXPRESSION; PHYSIOLOGY; DEFINES; TARGETS; GENOME AB Germinal centre B-cell-like diffuse large B-cell lymphoma(GCB-DLBCL) is a common malignancy, yet the signalling pathways that are deregulated and the factors leading to its systemic dissemination are poorly defined(1,2). Work in mice showed that sphingosine-1-phosphate receptor-2 (S1PR2), a G alpha 12 and G alpha 13 coupled receptor, promotes growth regulation and local confinement of germinal centre B cells(3,4). Recent deep sequencing studies of GCB-DLBCL have revealed mutations in many genes in this cancer, including in GNA13 (encoding G alpha 13) and S1PR2 (refs 5-7). Here we show, using in vitro and in vivo assays, that GCB-DLBCL-associated mutations occurring in S1PR2 frequently disrupt the receptor's Akt and migration inhibitory functions. G alpha 13-deficient mouse germinal centre B cells and human GCB-DLBCL cells were unable to suppress pAkt and migration in response to S1P, and G alpha 13-deficient mice developed germinal centre B-cell-derived lymphoma. Germinal centre B cells, unlike most lymphocytes, are tightly confined in lymphoid organs and do not recirculate. Remarkably, deficiency in G alpha 13, but not S1PR2, led to germinal centre B-cell dissemination into lymph and blood. GCB-DLBCL cell lines frequently carried mutations in the G alpha 13 effector ARHGEF1, and Arhgef1 deficiency also led to germinal centre B-cell dissemination. The incomplete phenocopy of G alpha 13- and S1PR2 deficiency led us to discover that P2RY8, an orphan receptor that is mutated in GCB-DLBCL and another germinal centre B-cell-derived malignancy, Burkitt's lymphoma, also represses germinal centre B-cell growth and promotes confinement via G alpha 13. These findings identify a G alpha 13-dependent pathway that exerts dual actions in suppressing growth and blocking dissemination of germinal centre B cells that is frequently disrupted in germinal centre B-cell-derived lymphoma. C1 [Muppidi, Jagan R.; Green, Jesse A.; Braun, Sterling E.; An, Jinping; Xu, Ying; Cyster, Jason G.] Univ Calif San Francisco, Dept Microbiol & Immunol, San Francisco, CA 94143 USA. [Muppidi, Jagan R.] Univ Calif San Francisco, Dept Med, San Francisco, CA 94143 USA. [Muppidi, Jagan R.; Green, Jesse A.; Braun, Sterling E.; An, Jinping; Xu, Ying; Cyster, Jason G.] Univ Calif San Francisco, Howard Hughes Med Inst, San Francisco, CA 94143 USA. [Schmitz, Roland; Xiao, Wenming; Staudt, Louis M.] NCI, Lymphoid Malignancies Branch, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. [Larsens, Adrien B.; Vaidehi, Nagarajan] City Hope Natl Med Ctr, Beckman Res Inst, Div Immunol, Duarte, CA 91010 USA. [Rosenwald, Andreas] Univ Wurzburg, Dept Pathol, D-97080 Wurzburg, Germany. [Ott, German] Robert Bosch Krankenhaus, Dept Clin Pathol, D-70376 Stuttgart, Germany. [Ott, German] Dr Margarete Fischer Bosch Inst Clin Pharmacol, D-70376 Stuttgart, Germany. [Gascoyne, Randy D.] British Columbia Canc Agcy, Vancouver, BC V5Z 1L3, Canada. [Rimsza, Lisa M.] Univ Arizona, Dept Pathol, Tucson, AZ 85724 USA. [Campo, Elias] Univ Barcelona, Hosp Clin, E-08036 Barcelona, Spain. [Jaffe, Elaine S.] NCI, Pathol Lab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. [Delabie, Jan] Univ Hosp, Rikshosp, Pathol Clin, N-0372 Oslo, Norway. [Smeland, Erlend B.] Univ Oslo, Univ Hosp, Rikshosp, Inst Canc Res, N-0310 Oslo, Norway. [Smeland, Erlend B.] Univ Oslo, Norwegian Radium Hosp, Fac Div, Ctr Canc Biomed, N-0310 Oslo, Norway. [Braziel, Rita M.] Oregon Hlth & Sci Univ, Portland, OR 97239 USA. [Tubbs, Raymond R.; Cook, J. R.] Cleveland Clin, Pathol & Lab Med Inst, Cleveland, OH 44195 USA. [Weisenburger, Dennis D.] City Hope Natl Med Ctr, Dept Pathol, Duarte, CA 91010 USA. [Chan, Wing C.] Univ Nebraska Med Ctr, Dept Pathol, Omaha, NE 68198 USA. [Chan, Wing C.] Univ Nebraska Med Ctr, Dept Microbiol, Omaha, NE 68198 USA. RP Cyster, JG (reprint author), Univ Calif San Francisco, Dept Microbiol & Immunol, San Francisco, CA 94143 USA. EM lstaudt@mail.nih.gov; jason.cyster@ucsf.edu RI Campo, elias/O-7192-2016 OI Campo, elias/0000-0001-9850-9793 FU Leukemia & Lymphoma Society; National Institutes of Health (NIH) [T32 DK007636, T32 CA1285835]; Dr Mildred Scheel Stiftung fur Krebsforschung (Deutsche Krebshilfe); NIH [GM097261, AI45073]; Lymphoma/Leukemia Molecular Profiling Project; NIH, National Cancer Institute, Center for Cancer Research FX We thank S. Coughlin for Gna13f/f and Arhgef1-/- mice and R. Proia for S1pr2-/- mice. We thank X. Geng and G. Doitsch for assistance with processing of human tonsil, A. Reboldi for discussion, and T. Arnon and O. Bannard for reading the manuscript. J.R.M. is supported by a Fellow Award from the Leukemia & Lymphoma Society and by National Institutes of Health (NIH) institutional training grants (T32 DK007636 and T32 CA1285835); R.S. is supported by the Dr Mildred Scheel Stiftung fur Krebsforschung (Deutsche Krebshilfe). N.V. was supported by NIH grant GM097261 for the modelling work. J.G.C. is an Investigator of the Howard Hughes Medical Institute. The human lymphoma samples were studied under the auspices of the Lymphoma/Leukemia Molecular Profiling Project. The work was supported in part by the Intramural Research Program of the NIH, National Cancer Institute, Center for Cancer Research, and NIH grant AI45073. NR 37 TC 51 Z9 52 U1 4 U2 13 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0028-0836 EI 1476-4687 J9 NATURE JI Nature PD DEC 11 PY 2014 VL 516 IS 7530 BP 254 EP + DI 10.1038/nature13765 PG 18 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA AW6ML UT WOS:000346383500047 PM 25274307 ER PT J AU Stasevich, TJ Hayashi-Takanaka, Y Sato, Y Maehara, K Ohkawa, Y Sakata-Sogawa, K Tokunaga, M Nagase, T Nozaki, N McNally, JG Kimura, H AF Stasevich, Timothy J. Hayashi-Takanaka, Yoko Sato, Yuko Maehara, Kazumitsu Ohkawa, Yasuyuki Sakata-Sogawa, Kumiko Tokunaga, Makio Nagase, Takahiro Nozaki, Naohito McNally, James G. Kimura, Hiroshi TI Regulation of RNA polymerase II activation by histone acetylation in single living cells SO NATURE LA English DT Article ID GLUCOCORTICOID-RECEPTOR; FRAP ANALYSIS; IN-VIVO; TRANSCRIPTION; PHOSPHORYLATION; CHROMATIN; DYNAMICS; REVEALS; ORGANIZATION; DEACETYLASES AB In eukaryotic cells, post-translational histone modifications have an important role in gene regulation. Starting with early work on histone acetylation 1, a variety of residue-specific modifications have now been linked to RNA polymerase II (RNAP2) activity(2,3), but it remains unclear if these markers are active regulators of transcription or just passive byproducts(4,5). This is because studies have traditionally relied on fixed cell populations, meaning temporal resolution is limited to minutes at best, and correlated factors may not actually be present in the same cell at the same time. Complementary approaches are therefore needed to probe the dynamic interplay of histone modifications and RNAP2 with higher temporal resolution in single living cells(2,5,6). Here we address this problem by developing a system to track residue-specific histone modifications and RNAP2 phosphorylation in living cells by fluorescence microscopy. This increases temporal resolution to the tens-of-seconds range. Our single-cell analysis reveals histone H3 lysine-27 acetylation at a gene locus can alter downstream transcription kinetics by as much as 50%, affecting two temporally separate events. First acetylation enhances the search kinetics of transcriptional activators, and later the acetylation accelerates the transition of RNAP2 from initiation to elongation. Signatures of the latter can be found genome-wide using chromatin immunoprecipitation followed by sequencing. We argue that this regulation leads to a robust and potentially tunable transcriptional response. C1 [Stasevich, Timothy J.; Hayashi-Takanaka, Yoko; Sato, Yuko; Kimura, Hiroshi] Osaka Univ, Grad Sch Frontier Biosci, Osaka 5650871, Japan. [Stasevich, Timothy J.] Colorado State Univ, Dept Biochem & Mol Biol, Ft Collins, CO 80523 USA. [Stasevich, Timothy J.] Howard Hughes Med Inst, Transcript Imaging Consortium, Ashburn, VA 20147 USA. [Hayashi-Takanaka, Yoko; Ohkawa, Yasuyuki; Kimura, Hiroshi] Japan Sci & Technol Agcy JST, Core Res Evolut Sci & Technol CREST, Saitama 3320012, Japan. [Hayashi-Takanaka, Yoko; Sato, Yuko; Kimura, Hiroshi] Tokyo Inst Technol, Grad Sch Biosci & Biotechnol, Dept Biol Sci, Yokohama, Kanagawa 2268501, Japan. [Maehara, Kazumitsu; Ohkawa, Yasuyuki] Kyushu Univ, Dept Adv Med Initiat, Fac Med, Fukuoka 8128582, Japan. [Sakata-Sogawa, Kumiko; Tokunaga, Makio] Tokyo Inst Technol, Grad Sch Biosci & Biotechnol, Dept Biol Informat, Yokohama, Kanagawa 2268501, Japan. [Sakata-Sogawa, Kumiko; Tokunaga, Makio] RIKEN Ctr Integrat Med Sci IMS, Yokohama, Kanagawa 2300045, Japan. [Nagase, Takahiro] Kazusa DNA Res Inst, Dept Biotechnol Res, Chiba 2920818, Japan. [Nozaki, Naohito] Mab Inst Inc, Sapporo, Hokkaido 00002, Japan. [McNally, James G.] NCI, Lab Receptor Biol & Gene Express, NIH, Bethesda, MD 20892 USA. [McNally, James G.] Helmholtz Zentrum Berlin, Inst Soft Matter & Funct Mat, D-14109 Berlin, Germany. RP Stasevich, TJ (reprint author), Osaka Univ, Grad Sch Frontier Biosci, Osaka 5650871, Japan. EM tim.stasevich@colostate.edu; hkimura@bio.titech.ac.jp RI U-ID, Kyushu/C-5291-2016; Ohkawa, Yasuyuki/C-4087-2016; OI Ohkawa, Yasuyuki/0000-0001-6440-9954; Kimura, Hiroshi/0000-0003-0854-083X FU Japan Society for the Promotion of Science (JSPS); Ministry of Education, Culture, Sports, Science and Technology of Japan; JSPS FX This work was supported by grants-in-aid from the Japan Society for the Promotion of Science (JSPS) and the Ministry of Education, Culture, Sports, Science and Technology of Japan. T.J.S. and Y.H.-T. were supported by JSPS fellowships. We thank T. Kanda, A. Kitamura and T. Morisaki for the mCh-H2B construct, D. Stavreva and G. Hager for the mCherry-NF1A1.1 construct, and F. Mueller and D. Mazza for comments on the manuscript. NR 44 TC 61 Z9 61 U1 9 U2 40 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0028-0836 EI 1476-4687 J9 NATURE JI Nature PD DEC 11 PY 2014 VL 516 IS 7530 BP 272 EP + DI 10.1038/nature13714 PG 18 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA AW6ML UT WOS:000346383500051 PM 25252976 ER PT J AU Tosh, DK Finley, A Paoletta, S Moss, SM Gao, ZG Gizewski, ET Auchampach, JA Salvemini, D Jacobson, KA AF Tosh, Dilip K. Finley, Amanda Paoletta, Silvia Moss, Steven M. Gao, Zhan-Guo Gizewski, Elizabeth T. Auchampach, John A. Salvemini, Daniela Jacobson, Kenneth A. TI In Vivo Phenotypic Screening for Treating Chronic Neuropathic Pain: Modification of C2-Arylethynyl Group of Conformationally Constrained A(3) Adenosine Receptor Agonists SO JOURNAL OF MEDICINAL CHEMISTRY LA English DT Article ID MEDICINAL CHEMISTRY; DERIVATIVES; BINDING; POTENT; ACTIVATION; INHIBITOR; LIGANDS; DESIGN; MOTOR; MICE AB (N)-Methanocarba adenosine 5'-methyluronamides containing 2-arylethynyl groups were synthesized as A3 adenosine receptor (AR) agonists and screened in vivo (po) for reduction of neuropathic pain. A small N-6-methyl group maintained binding affinity, with human > mouse A3AR and MW < 500 and other favorable physicochemical properties. Emax (maximal efficacy in a mouse chronic constriction injury pain model) of previously characterized A3AR agonist, 2-(3,4-difluorophenylethynyl)-N-6-(3-chlorobenzyl) derivative 6a, MRS5698, was surpassed. More efficacious analogues (in vivo) contained the following C2-arylethynyl groups: pyrazin-2-yl 23 (binding Ki, hA(3)AR, nM 1.8), fur-2-yl 27 (0.6), thien-2-yl 32 (0.6) and its 5-chloro 33, MRS5980 (0.7) and 5-bromo 34 (0.4) equivalents, and physiologically unstable ferrocene 36, MRS5979 (2.7). 33 and 36 displayed particularly long in vivo duration (>3 h). Selected analogues were docked to an A3AR homology model to explore the environment of receptor-bound C2 and N-6 groups. Various analogues bound with mu M affinity at off-target biogenic amine (M-2, 5HT(2A), beta(3), 5HT(2B), 5HT(2C), and alpha(2C)) or other receptors. Thus, we have expanded the structural range of orally active A3AR agonists for chronic pain treatment. C1 [Tosh, Dilip K.; Paoletta, Silvia; Moss, Steven M.; Gao, Zhan-Guo; Jacobson, Kenneth A.] NIDDK, Mol Recognit Sect, Bioorgan Chem Lab, NIH, Bethesda, MD 20892 USA. [Gizewski, Elizabeth T.; Auchampach, John A.] Med Coll Wisconsin, Dept Pharmacol, Milwaukee, WI 53226 USA. [Finley, Amanda; Salvemini, Daniela] St Louis Univ, Sch Med, Dept Pharmacol & Physiol Sci, St Louis, MO 63104 USA. RP Jacobson, KA (reprint author), NIDDK, Mol Recognit Sect, Bioorgan Chem Lab, NIH, Bldg 8A,Room B1A-19, Bethesda, MD 20892 USA. EM kajacobs@helix.nih.gov RI Jacobson, Kenneth/A-1530-2009 OI Jacobson, Kenneth/0000-0001-8104-1493 FU National Institutes of Health [R01HL077707]; National Institute of Mental Health's Psychoactive Drug Screening Program [HHSN-271-2008-00025-C] FX We thank Dr. John Lloyd and Dr. Noel Whittaker (NIDDK) for mass spectral determinations. This research was supported by the National Institutes of Health (Intramural Research Program of the NIDDK and R01HL077707). We thank Dr. Bryan L. Roth (University of North Carolina at Chapel Hill) and National Institute of Mental Health's Psychoactive Drug Screening Program (contract no. HHSN-271-2008-00025-C) for screening data. NR 46 TC 15 Z9 15 U1 0 U2 18 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0022-2623 EI 1520-4804 J9 J MED CHEM JI J. Med. Chem. PD DEC 11 PY 2014 VL 57 IS 23 BP 9901 EP 9914 DI 10.1021/jm501021n PG 14 WC Chemistry, Medicinal SC Pharmacology & Pharmacy GA AW5NH UT WOS:000346321200014 PM 25422861 ER PT J AU Kang, Z Yu, Y Zhu, YJ Davis, S Walker, R Meltzer, PS Helman, LJ Cao, L AF Kang, Z. Yu, Y. Zhu, Y. J. Davis, S. Walker, R. Meltzer, P. S. Helman, L. J. Cao, L. TI Downregulation of IGFBP2 is associated with resistance to IGF1R therapy in rhabdomyosarcoma SO ONCOGENE LA English DT Article DE IGF1R; IGFBP2; rhabdomyosarcoma; antibody therapy; drug resistance; drug combination ID GROWTH-FACTOR-I; FACTOR-BINDING PROTEIN-2; FACTOR RECEPTOR INHIBITORS; CHILDRENS ONCOLOGY GROUP; PHASE-II; CANDIDATE BIOMARKER; MONOCLONAL-ANTIBODY; PROSTATE-CANCER; INSULIN; TARGET AB Agents targeting the insulin-like growth factor-1 receptor (IGF1R) are in clinical development, but, despite some initial success of single agents in sarcoma, response rates are low with brief durations. Thus, it is important to identify markers predictive of response, to understand mechanisms of resistance, and to explore combination therapies. In this study, we found that, although associated with PAX3-FKHR translocation, increased IGF1R level is an independent prognostic marker for worse overall survival, particularly in patients with PAX3-FKHR-positive rhabdomyosarcoma (RMS). IGF1R antibody-resistant RMS cells were generated using an in vivo model. Expression analysis indicated that IGFBP2 is both the most affected gene in the insulin-like growth factor (IGF) signaling pathway and the most significantly downregulated gene in the resistant lines, indicating that there is a strong selection to repress IGFBP2 expression in tumor cells resistant to IGF1R antibody. IGFBP2 is inhibitory to IGF1R phosphorylation and its signaling. Similar to antibodies to IGF1/2 or IGF2, the addition of exogenous IGFBP2 potentiates the activity of IGF1R antibody against the RMS cells, and it reverses the resistance to IGF1R antibody. In contrast to IGF1R, lower expression of IGFBP2 is associated with poorer overall survival, consistent with its inhibitory activity found in this study. Finally, blocking downstream Protein kinase B (AKT) activation with Phosphatidylinositide 3-kinases (PI3K)- or mammalian target of rapamycin (mTOR)-specific inhibitors significantly sensitized the resistant cells to the IGF1R antibody. These findings show that constitutive IGFBP2 downregulation may represent a novel mechanism for acquired resistance to IGF1R therapeutic antibody in vivo and suggest various drug combinations to enhance antibody activity and to overcome resistance. C1 [Kang, Z.; Yu, Y.; Zhu, Y. J.; Davis, S.; Walker, R.; Meltzer, P. S.; Cao, L.] NCI, Genet Branch, Ctr Canc Res, Bethesda, MD 20892 USA. [Kang, Z.] Leidos Biomed Res Inc, Canc Res Technol Program, Frederick, MD USA. [Helman, L. J.] NCI, Ctr Canc Res, Pediatr Oncol Branch, Bethesda, MD 20892 USA. RP Cao, L (reprint author), NCI, Genet Branch, 37 Convent Dr,MSC 4265, Bethesda, MD 20892 USA. EM caoli@mail.nih.gov OI Davis, Sean/0000-0002-8991-6458 FU Intramural Research Program of the US National Cancer Institute (NCI); NCI; NIH [N01-CO-12400] FX This research was supported by the Intramural Research Program of the US National Cancer Institute (NCI). This project was also funded in part with federal funds from the NCI, NIH, under contract N01-CO-12400. NR 43 TC 5 Z9 5 U1 2 U2 5 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0950-9232 EI 1476-5594 J9 ONCOGENE JI Oncogene PD DEC 11 PY 2014 VL 33 IS 50 BP 5697 EP 5705 DI 10.1038/onc.2013.509 PG 9 WC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity GA AW2AB UT WOS:000346089300005 PM 24292683 ER PT J AU Schrier, RW Abebe, KZ Perrone, RD Torres, VE Braun, WE Steinman, TI Winklhofer, FT Brosnahan, G Czarnecki, PG Hogan, MC Miskulin, DC Rahbari-Oskoui, FF Grantham, JJ Harris, PC Flessner, MF Bae, KT Moore, CG Chapman, AB AF Schrier, Robert W. Abebe, Kaleab Z. Perrone, Ronald D. Torres, Vicente E. Braun, William E. Steinman, Theodore I. Winklhofer, Franz T. Brosnahan, Godela Czarnecki, Peter G. Hogan, Marie C. Miskulin, Dana C. Rahbari-Oskoui, Frederic F. Grantham, Jared J. Harris, Peter C. Flessner, Michael F. Bae, Kyongtae T. Moore, Charity G. Chapman, Arlene B. CA HALT-PKD Trial Investigators TI Blood Pressure in Early Autosomal Dominant Polycystic Kidney Disease SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Article ID VOLUME PROGRESSION; CONVERTING ENZYME; RENAL-DISEASE; OUTCOMES; RENIN; HYPERTENSION; ALDOSTERONE; INHIBITION; TRIALS; RISK AB BACKGROUND Hypertension is common in autosomal dominant polycystic kidney disease (ADPKD) and is associated with increased total kidney volume, activation of the renin-angiotensin-aldosterone system, and progression of kidney disease. METHODS In this double-blind, placebo-controlled trial, we randomly assigned 558 hypertensive participants with ADPKD (15 to 49 years of age, with an estimated glomerular filtration rate [GFR] >60 ml per minute per 1.73 m(2) of body-surface area) to either a standard blood-pressure target (120/70 to 130/80 mm Hg) or a low blood-pressure target (95/60 to 110/75 mm Hg) and to either an angiotensin-converting-enzyme inhibitor (lisinopril) plus an angiotensin-receptor blocker (telmisartan) or lisinopril plus placebo. The primary outcome was the annual percentage change in the total kidney volume. RESULTS The annual percentage increase in total kidney volume was significantly lower in the low-blood-pressure group than in the standard-blood-pressure group (5.6% vs. 6.6%, P = 0.006), without significant differences between the lisinopril-telmisartan group and the lisinopril-placebo group. The rate of change in estimated GFR was similar in the two medication groups, with a negative slope difference in the short term in the low-blood-pressure group as compared with the standard-blood-pressure group (P<0.001) and a marginally positive slope difference in the long term (P = 0.05). The left-ventricular-mass index decreased more in the low-blood-pressure group than in the standard-blood-pressure group (-1.17 vs. -0.57 g per square meter per year, P<0.001); urinary albumin excretion was reduced by 3.77% with the low-pressure target and increased by 2.43% with the standard target (P<0.001). Dizziness and light-headedness were more common in the low-blood-pressure group than in the standard-blood-pressure group (80.7% vs. 69.4%, P = 0.002). CONCLUSIONS In early ADPKD, the combination of lisinopril and telmisartan did not significantly alter the rate of increase in total kidney volume. As compared with standard blood-pressure control, rigorous blood-pressure control was associated with a slower increase in total kidney volume, no overall change in the estimated GFR, a greater decline in the left-ventricular-mass index, and greater reduction in urinary albumin excretion. C1 [Schrier, Robert W.; Brosnahan, Godela] Univ Colorado, Denver, CO 80202 USA. [Abebe, Kaleab Z.; Bae, Kyongtae T.; Moore, Charity G.] Univ Pittsburgh, Sch Med, Pittsburgh, PA USA. [Perrone, Ronald D.; Miskulin, Dana C.] Tufts Med Ctr, Boston, MA USA. [Steinman, Theodore I.; Czarnecki, Peter G.] Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. [Torres, Vicente E.; Hogan, Marie C.; Harris, Peter C.] Mayo Clin, Coll Med, Rochester, MN USA. [Braun, William E.] Cleveland Clin, Cleveland, OH USA. [Winklhofer, Franz T.; Grantham, Jared J.] Univ Kansas, Med Ctr, Kansas City, MO USA. [Rahbari-Oskoui, Frederic F.; Chapman, Arlene B.] Emory Univ, Sch Med, Atlanta, GA USA. [Flessner, Michael F.] NIH, Bethesda, MD 20892 USA. RP Schrier, RW (reprint author), Univ Colorado, Div Renal Dis & Hypertens, Aurora, CO 80045 USA. EM robert.schrier@ucdenver.edu OI Abebe, Kaleab/0000-0002-3644-8419 FU National Institute of Diabetes and Digestive and Kidney Diseases FX Funded by the National Institute of Diabetes and Digestive and Kidney Diseases and others; HALT-PKD [Study A] ClinicalTrials.gov number, NCT00283686. NR 35 TC 75 Z9 76 U1 2 U2 12 PU MASSACHUSETTS MEDICAL SOC PI WALTHAM PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA SN 0028-4793 EI 1533-4406 J9 NEW ENGL J MED JI N. Engl. J. Med. PD DEC 11 PY 2014 VL 371 IS 24 BP 2255 EP 2266 DI 10.1056/NEJMoa1402685 PG 12 WC Medicine, General & Internal SC General & Internal Medicine GA AW1KQ UT WOS:000346048800006 PM 25399733 ER PT J AU Torres, VE Abebe, KZ Chapman, AB Schrier, RW Braun, WE Steinman, TI Winklhofer, FT Brosnahan, G Czarnecki, PG Hogan, MC Miskulin, DC Rahbari-Oskoui, FF Grantham, JJ Harris, PC Flessner, MF Moore, CG Perrone, RD AF Torres, Vicente E. Abebe, Kaleab Z. Chapman, Arlene B. Schrier, Robert W. Braun, William E. Steinman, Theodore I. Winklhofer, Franz T. Brosnahan, Godela Czarnecki, Peter G. Hogan, Marie C. Miskulin, Dana C. Rahbari-Oskoui, Frederic F. Grantham, Jared J. Harris, Peter C. Flessner, Michael F. Moore, Charity G. Perrone, Ronald D. CA HALT-PKD Trial Investigators TI Angiotensin Blockade in Late Autosomal Dominant Polycystic Kidney Disease SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Article ID BLOOD-PRESSURE CONTROL; COMBINATION THERAPY; ALDOSTERONE SYSTEM; CONVERTING-ENZYME; DIABETIC-NEPHROPATHY; RECEPTOR BLOCKER; ACE-INHIBITOR; RENAL-DISEASE; RENIN; METAANALYSIS AB BACKGROUND Hypertension develops early in patients with autosomal dominant polycystic kidney disease (ADPKD) and is associated with disease progression. The renin-angiotensin-aldosterone system (RAAS) is implicated in the pathogenesis of hypertension in patients with ADPKD. Dual blockade of the RAAS may circumvent compensatory mechanisms that limit the efficacy of monotherapy with an angiotensin-converting- enzyme (ACE) inhibitor or angiotensin II-receptor blocker (ARB). METHODS In this double-blind, placebo-controlled trial, we randomly assigned 486 patients, 18 to 64 years of age, with ADPKD (estimated glomerular filtration rate [GFR], 25 to 60 ml per minute per 1.73 m(2) of body-surface area) to receive an ACE inhibitor (lisinopril) and placebo or lisinopril and an ARB (telmisartan), with the doses adjusted to achieve a blood pressure of 110/70 to 130/80 mm Hg. The composite primary outcome was the time to death, end-stage renal disease, or a 50% reduction from the baseline estimated GFR. Secondary outcomes included the rates of change in urinary aldosterone and albumin excretion, frequency of hospitalizations for any cause and for cardiovascular causes, incidence of pain, frequency of ADPKD-related symptoms, quality of life, and adverse study-medication effects. Patients were followed for 5 to 8 years. RESULTS There was no significant difference between the study groups in the incidence of the composite primary outcome (hazard ratio with lisinopril-telmisartan, 1.08; 95% confidence interval, 0.82 to 1.42). The two treatments controlled blood pressure and lowered urinary aldosterone excretion similarly. The rates of decline in the estimated GFR, urinary albumin excretion, and other secondary outcomes and adverse events, including hyperkalemia and acute kidney injury, were also similar in the two groups. CONCLUSIONS Monotherapy with an ACE inhibitor was associated with blood-pressure control in most patients with ADPKD and stage 3 chronic kidney disease. The addition of an ARB did not alter the decline in the estimated GFR. C1 [Torres, Vicente E.; Hogan, Marie C.; Harris, Peter C.] Mayo Clin, Coll Med, Rochester, MN 55901 USA. [Abebe, Kaleab Z.; Moore, Charity G.] Univ Pittsburgh, Sch Med, Pittsburgh, PA USA. [Chapman, Arlene B.; Rahbari-Oskoui, Frederic F.] Emory Univ, Sch Med, Atlanta, GA USA. [Schrier, Robert W.; Brosnahan, Godela] Univ Colorado, Hlth Sci Ctr, Denver, CO USA. [Braun, William E.] Cleveland Clin, Cleveland, OH USA. [Steinman, Theodore I.; Czarnecki, Peter G.] Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. [Miskulin, Dana C.; Perrone, Ronald D.] Tufts Med Ctr, Boston, MA USA. [Winklhofer, Franz T.; Grantham, Jared J.] Univ Kansas, Med Ctr, Kansas City, MO USA. [Flessner, Michael F.] NIH, Bethesda, MD 20892 USA. RP Torres, VE (reprint author), Mayo Clin, Div Nephrol & Hypertens, Rochester, MN 55901 USA. EM torres.vicente@mayo.edu OI Abebe, Kaleab/0000-0002-3644-8419 FU National Institute of Diabetes and Digestive and Kidney Diseases FX Funded by the National Institute of Diabetes and Digestive and Kidney Diseases and others; HALT-PKD [Study B] ClinicalTrials.gov number, NCT01885559. NR 36 TC 50 Z9 52 U1 2 U2 10 PU MASSACHUSETTS MEDICAL SOC PI WALTHAM PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA SN 0028-4793 EI 1533-4406 J9 NEW ENGL J MED JI N. Engl. J. Med. PD DEC 11 PY 2014 VL 371 IS 24 BP 2267 EP 2276 DI 10.1056/NEJMoa1402686 PG 10 WC Medicine, General & Internal SC General & Internal Medicine GA AW1KQ UT WOS:000346048800007 PM 25399731 ER PT J AU Han, XS Yabroff, KR Robbins, AS Zheng, ZY Jamal, A AF Han, Xuesong Yabroff, K. Robin Robbins, Anthony S. Zheng, Zhiyuan Jamal, Ahmedin TI Dependent Coverage and Use of Preventive Care under the Affordable Care Act SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Letter ID HEALTH-INSURANCE; YOUNG-ADULTS C1 [Han, Xuesong; Robbins, Anthony S.; Zheng, Zhiyuan; Jamal, Ahmedin] Amer Canc Soc, Atlanta, GA 30329 USA. [Yabroff, K. Robin] NCI, Rockville, MD USA. RP Han, XS (reprint author), Amer Canc Soc, Atlanta, GA 30329 USA. EM xuesong.han@cancer.org OI Yabroff, K. Robin/0000-0003-0644-5572 FU Intramural NIH HHS [Z99 CA999999] NR 4 TC 6 Z9 6 U1 0 U2 4 PU MASSACHUSETTS MEDICAL SOC PI WALTHAM PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA SN 0028-4793 EI 1533-4406 J9 NEW ENGL J MED JI N. Engl. J. Med. PD DEC 11 PY 2014 VL 371 IS 24 BP 2341 EP 2342 DI 10.1056/NEJMc1406586 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA AW1KQ UT WOS:000346048800027 PM 25494285 ER PT J AU Gibbs, KD McGready, J Bennett, JC Griffin, K AF Gibbs, Kenneth D., Jr. McGready, John Bennett, Jessica C. Griffin, Kimberly TI Biomedical Science Ph.D. Career Interest Patterns by Race/Ethnicity and Gender SO PLOS ONE LA English DT Article ID DOUBLE BIND; DIVERSITY; WORKFORCE; COLOR; UNDERGRADUATE; EDUCATION; FACULTY; WOMEN AB Increasing biomedical workforce diversity remains a persistent challenge. Recent reports have shown that biomedical sciences (BMS) graduate students become less interested in faculty careers as training progresses; however, it is unclear whether or how the career preferences of women and underrepresented minority (URM) scientists change in manners distinct from their better-represented peers. We report results from a survey of 1500 recent American BMS Ph. D. graduates (including 276 URMs) that examined career preferences over the course of their graduate training experiences. On average, scientists from all social backgrounds showed significantly decreased interest in faculty careers at research universities, and significantly increased interest in non-research careers at Ph. D. completion relative to entry. However, group differences emerged in overall levels of interest (at Ph.D. entry and completion), and the magnitude of change in interest in these careers. Multiple logistic regression showed that when controlling for career pathway interest at Ph.D. entry, first-author publication rate, faculty support, research self-efficacy, and graduate training experiences, differences in career pathway interest between social identity groups persisted. All groups were less likely than men from well-represented (WR) racial/ethnic backgrounds to report high interest in faculty careers at research-intensive universities (URM men: OR 0.60, 95% CI: 0.36-0.98, p=0.04; WR women: OR: 0.64, 95% CI: 0.47-0.89, p=0.008; URM women: OR: 0.46, 95% CI: 0.30-0.71, p, 0.001), and URM women were more likely than all other groups to report high interest in non-research careers (OR: 1.93, 95% CI: 1.28-2.90, p=0.002). The persistence of disparities in the career interests of Ph. D. recipients suggests that a supply- side (or "pipeline'') framing of biomedical workforce diversity challenges may limit the effectiveness of efforts to attract and retain the best and most diverse workforce. We propose incorporation of an ecological perspective of career development when considering strategies to enhance the biomedical workforce and professoriate through diversity. C1 [Gibbs, Kenneth D., Jr.] NCI, Canc Prevent Fellowship Program, Canc Prevent Div, Bethesda, MD 20892 USA. [Gibbs, Kenneth D., Jr.] NCI, Sci Res & Technol Branch, Behav Res Program, Div Canc Control & Populat Sci, Bethesda, MD 20892 USA. [McGready, John] Johns Hopkins Bloomberg Sch Publ Hlth, Dept Biostat, Baltimore, MD USA. [Bennett, Jessica C.; Griffin, Kimberly] Univ Maryland, Dept Counseling Higher Educ & Special Educ, College Pk, MD 20742 USA. RP Gibbs, KD (reprint author), NCI, Canc Prevent Fellowship Program, Canc Prevent Div, Bethesda, MD 20892 USA. EM kenneth.gibbs@nih.gov; kgriff29@umd.edu OI Gibbs, Kenneth/0000-0002-3532-5396 FU Burroughs Wellcome Fund FX This work was supported by the Burroughs Wellcome Fund. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 47 TC 24 Z9 24 U1 10 U2 34 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 10 PY 2014 VL 9 IS 12 AR e114736 DI 10.1371/journal.pone.0114736 PG 18 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA AW9YP UT WOS:000346611400073 PM 25493425 ER PT J AU Kuwabara, H Heishman, SJ Brasic, JR Contoreggi, C Cascella, N Mackowick, KM Taylor, R Rousset, O Willis, W Huestis, MA Concheiro, M Wand, G Wong, DF Volkow, ND AF Kuwabara, Hiroto Heishman, Stephen J. Brasic, James R. Contoreggi, Carlo Cascella, Nicola Mackowick, Kristen M. Taylor, Richard Rousset, Olivier Willis, William Huestis, Marilyn A. Concheiro, Marta Wand, Gary Wong, Dean F. Volkow, Nora D. TI Mu Opioid Receptor Binding Correlates with Nicotine Dependence and Reward in Smokers SO PLOS ONE LA English DT Article ID POSITRON-EMISSION-TOMOGRAPHY; STRIATAL DOPAMINE RELEASE; KNOCK-OUT MICE; DENICOTINIZED CIGARETTE; WITHDRAWAL SYMPTOMS; TOBACCO WITHDRAWAL; HUMAN BRAIN; SMOKING; FMRI; CARFENTANIL AB The rewarding effects of nicotine are associated with activation of nicotine receptors. However, there is increasing evidence that the endogenous opioid system is involved in nicotine's rewarding effects. We employed PET imaging with [C-11] carfentanil to test the hypotheses that acute cigarette smoking increases release of endogenous opioids in the human brain and that smokers have an upregulation of mu opioid receptors (MORs) when compared to nonsmokers. We found no significant changes in binding potential (BPND) of [C-11] carfentanil between the placebo and the active cigarette sessions, nor did we observe differences in MOR binding between smokers and nonsmokers. Interestingly, we showed that in smokers MOR availability in bilateral superior temporal cortices during the placebo condition was negatively correlated with scores on the Fagerstrom Test for Nicotine Dependence (FTND). Also in smokers, smoking-induced decreases in [C-11] carfentanil binding in frontal cortical regions were associated with self-reports of cigarette liking and wanting. Although we did not show differences between smokers and nonsmokers, the negative correlation with FTND corroborates the role of MORs in superior temporal cortices in nicotine addiction and provides preliminary evidence of a role of endogenous opioid signaling in frontal cortex in nicotine reward. C1 [Kuwabara, Hiroto; Brasic, James R.; Rousset, Olivier; Willis, William; Wong, Dean F.] Johns Hopkins Univ, Russell H Morgan Dept Radiol & Radiol Sci, Baltimore, MD 21218 USA. [Heishman, Stephen J.; Cascella, Nicola; Wong, Dean F.] Johns Hopkins Univ, Dept Psychiat, Baltimore, MD USA. [Wand, Gary] Johns Hopkins Univ, Dept Med, Baltimore, MD USA. [Wong, Dean F.] Johns Hopkins Univ, Dept Neurosci, Baltimore, MD USA. [Heishman, Stephen J.; Contoreggi, Carlo; Mackowick, Kristen M.; Taylor, Richard; Huestis, Marilyn A.; Concheiro, Marta] NIDA, Intramural Res Program, Baltimore, MD USA. [Volkow, Nora D.] NIDA, Rockville, MD USA. RP Kuwabara, H (reprint author), Johns Hopkins Univ, Russell H Morgan Dept Radiol & Radiol Sci, Baltimore, MD 21218 USA. EM hkuwaba1@jhmi.edu FU NIH, National Institute on Drug Abuse; NIDA [K24 DA000412]; Radiology Internal Funds; National Center for Advancing Translational Sciences (NCATS) a component of the National Institutes of Health (NIH) [UL1 TR 001079]; NIH Roadmap for Medical Research FX Financial support was provided by the Intramural Research Program of NIH, National Institute on Drug Abuse (SH, CC, KM, RT), and an award from NIDA, K24 DA000412 (DFW), as well as Radiology Internal Funds (DFW). All authors declare no conflicts of interest. Additionally, resources were provided by the Johns Hopkins Institute for Clinical and Translational Research (ICTR), which is funded in part by grant number UL1 TR 001079 from the National Center for Advancing Translational Sciences (NCATS) a component of the National Institutes of Health (NIH), and NIH Roadmap for Medical Research. Its contents are solely the responsibility of the authors and do not necessarily represent the official view of the Johns Hopkins ICTR, NCATS or NIH. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 49 TC 5 Z9 5 U1 0 U2 11 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA SN 1932-6203 J9 PLOS ONE JI PLoS One PD DEC 10 PY 2014 VL 9 IS 12 AR e113694 DI 10.1371/journal.pone.0113694 PG 15 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA AW9YP UT WOS:000346611400017 PM 25493427 ER PT J AU Cargnin, F Nechiporuk, T Mullendorff, K Stumpo, DJ Blackshear, PJ Ballas, N Mandel, G AF Cargnin, Francesca Nechiporuk, Tamilla Muellendorff, Karin Stumpo, Deborah J. Blackshear, Perry J. Ballas, Nurit Mandel, Gail TI An RNA Binding Protein Promotes Axonal Integrity in Peripheral Neurons by Destabilizing REST SO JOURNAL OF NEUROSCIENCE LA English DT Article DE axonal integrity; peripheral nervous system; post-transcriptional regulation; REST; RNA binding protein; ZFP36L2 ID RESTRICTIVE SILENCER FACTOR; MESSENGER-RNA; GENE-EXPRESSION; STEM-CELLS; TRANSCRIPTIONAL REPRESSION; HISTONE DEACETYLASE; INJURY-RESPONSE; TARGET GENES; TRISTETRAPROLIN; NETWORKS AB The RE1 Silencing Transcription Factor (REST) acts as a governor of the mature neuronal phenotype by repressing a large consortium of neuronal genes in non-neuronal cells. In the developing nervous system, REST is present in progenitors and downregulated at terminal differentiation to promote acquisition of mature neuronal phenotypes. Paradoxically, REST is still detected in some regions of the adult nervous system, but how REST levels are regulated, and whether REST can still repress neuronal genes, is not known. Here, we report that homeostatic levels of REST are maintained in mature peripheral neurons by a constitutive post-transcriptional mechanism. Specifically, using a three-hybrid genetic screen, we identify the RNA binding protein, ZFP36L2, associated previously only with female fertility and hematopoiesis, and show that it regulates REST mRNA stability. Dorsal root ganglia in Zfp36l2 knock-out mice, or wild-type ganglia expressing ZFP36L2 shRNA, show higher steady-state levels of Rest mRNA and protein, and extend thin and disintegrating axons. This phenotype is due, at least in part, to abnormally elevated REST levels in the ganglia because the axonal phenotype is attenuated by acute knockdown of REST in Zfp36l2 KO DRG explants. The higher REST levels result in lower levels of target genes, indicating that REST can still fine-tune gene expression through repression. Thus, REST levels are titrated in mature peripheral neurons, in part through a ZFP36L2-mediated post-transcriptional mechanism, with consequences for axonal integrity. C1 [Cargnin, Francesca; Nechiporuk, Tamilla; Muellendorff, Karin; Mandel, Gail] Oregon Hlth & Sci Univ, Vollum Inst, Howard Hughes Med Inst, Portland, OR 97239 USA. [Stumpo, Deborah J.; Blackshear, Perry J.] NIEHS, Lab Signal Transduct, Res Triangle Pk, NC 27709 USA. [Ballas, Nurit] SUNY Stony Brook, Dept Biochem & Cell Biol, Stony Brook, NY 11794 USA. RP Mandel, G (reprint author), Oregon Hlth & Sci Univ, Vollum Inst, Howard Hughes Med Inst, 3181 SW Sam Jackson Pk Rd, Portland, OR 97239 USA. EM mandelg@ohsu.edu FU Intramural Research Program of the National Institutes of Health, National Institute of Environmental Health Sciences; National Institutes of Health [NS22518] FX This work was supported in part by the Intramural Research Program of the National Institutes of Health, National Institute of Environmental Health Sciences to D.J.S. and P.J.B. and National Institutes of Health Grant NS22518 to G.M., G.M. is an Investigator of the Howard Hughes Medical Institute. We thank Andrea Ansari and Travis Polston for excellent support in genotyping and mouse husbandry; Glen Corson and Daniel Cawley for expertise in generating the monoclonal antibodies to REST; and Drs. Wi S. Lai and Stephanie N. Hicks for performing the gel shift analyses. NR 57 TC 2 Z9 2 U1 1 U2 8 PU SOC NEUROSCIENCE PI WASHINGTON PA 11 DUPONT CIRCLE, NW, STE 500, WASHINGTON, DC 20036 USA SN 0270-6474 J9 J NEUROSCI JI J. Neurosci. PD DEC 10 PY 2014 VL 34 IS 50 BP 16650 EP 16661 DI 10.1523/JNEUROSCI.1650-14.2014 PG 12 WC Neurosciences SC Neurosciences & Neurology GA AW3MS UT WOS:000346191500012 PM 25505318 ER PT J AU Shiels, MS Gibson, T Sampson, J Albanes, D Andreotti, G Freeman, LB de Gonzalez, AB Caporaso, N Curtis, RE Elena, J Freedman, ND Robien, K Black, A Morton, LM AF Shiels, Meredith S. Gibson, Todd Sampson, Joshua Albanes, Demetrius Andreotti, Gabriella Freeman, Laura Beane de Gonzalez, Amy Berrington Caporaso, Neil Curtis, Rochelle E. Elena, Joanne Freedman, Neal D. Robien, Kim Black, Amanda Morton, Lindsay M. TI Cigarette Smoking Prior to First Cancer and Risk of Second Smoking-Associated Cancers Among Survivors of Bladder, Kidney, Head and Neck, and Stage I Lung Cancers SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article ID PRIMARY TUMORS; COMPETING RISKS; CESSATION; HEALTH; DIAGNOSIS; DESIGN; TRIAL AB Purpose Data on smoking and second cancer risk among cancer survivors are limited. We assessed associations between smoking before first cancer diagnosis and risk of second primary smoking-associated cancers among survivors of lung (stage I), bladder, kidney, and head/neck cancers. Methods Data were pooled from 2,552 patients with stage I lung cancer, 6,386 with bladder cancer, 3,179 with kidney cancer, and 2,967 with head/neck cancer from five cohort studies. We assessed the association between prediagnostic smoking and second smoking-associated cancer risk with proportional hazards regression, and compared these estimates to those for first smoking-associated cancers in all cohort participants. Results Compared with never smoking, current smoking of >= 20 cigarettes per day was associated with increased second smoking-associated cancer risk among survivors of stage I lung (hazard ratio [HR] = 3.26; 95% CI, 0.92 to 11.6), bladder (HR = 3.67; 95% CI, 2.25 to 5.99), head/neck (HR = 4.45; 95% CI, 2.56 to 7.73), and kidney cancers (HR = 5.33; 95% CI, 2.55 to 11.1). These estimates were similar to those for first smoking-associated cancer among all cohort participants (HR = 5.41; 95% CI, 5.23 to 5.61). The 5-year cumulative incidence of second smoking-associated cancers ranged from 3% to 8% in this group of cancer survivors. Conclusion Understanding risk factors for second cancers among cancer survivors is crucial. Our data indicate that cigarette smoking before first cancer diagnosis increases second cancer risk among cancer survivors, and elevated cancer risk in these survivors is likely due to increased smoking prevalence. The high 5-year cumulative risks of smoking-associated cancers among current smoking survivors of stage I lung, bladder, kidney, and head/neck cancers highlight the importance of smoking cessation in patients with cancer. (C) 2014 by American Society of Clinical Oncology C1 [Shiels, Meredith S.; Gibson, Todd; Sampson, Joshua; Albanes, Demetrius; Andreotti, Gabriella; Freeman, Laura Beane; de Gonzalez, Amy Berrington; Caporaso, Neil; Curtis, Rochelle E.; Elena, Joanne; Freedman, Neal D.; Black, Amanda; Morton, Lindsay M.] NCI, Bethesda, MD 20892 USA. [Gibson, Todd] St Jude Childrens Res Hosp, Memphis, TN USA. [Robien, Kim] George Washington Univ, Milken Inst Sch Publ Hlth, Washington, DC USA. RP Shiels, MS (reprint author), NCI, Div Canc Epidemiol & Genet, 9609 Med Ctr Dr,Room 6E-218 MSC 9767, Bethesda, MD 20892 USA. EM shielsms@mail.nih.gov RI Morton, Lindsay/B-5234-2015; Albanes, Demetrius/B-9749-2015; Beane Freeman, Laura/C-4468-2015; Freedman, Neal/B-9741-2015 OI Morton, Lindsay/0000-0001-9767-2310; Beane Freeman, Laura/0000-0003-1294-4124; Freedman, Neal/0000-0003-0074-1098 FU National Cancer Institute, National Institutes of Health; National Cancer Institute [R01 CA39742] FX Supported in part by the Intramural program of the National Cancer Institute, National Institutes of Health. The Iowa Women's Health Study was funded by National Cancer Institute Grant No. R01 CA39742. NR 34 TC 14 Z9 14 U1 2 U2 13 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 10 PY 2014 VL 32 IS 35 BP 3989 EP U130 DI 10.1200/JCO.2014.56.8220 PG 14 WC Oncology SC Oncology GA AU9IK UT WOS:000345905100015 PM 25385740 ER PT J AU Gibson, TM Park, Y Robien, K Shiels, MS Black, A Sampson, JN Purdue, MP Freeman, LEB Andreotti, G Weinstein, SJ Albanes, D Fraumeni, JF Curtis, RE de Gonzalez, AB Morton, LM AF Gibson, Todd M. Park, Yikyung Robien, Kim Shiels, Meredith S. Black, Amanda Sampson, Joshua N. Purdue, Mark P. Freeman, Laura E. Beane Andreotti, Gabriella Weinstein, Stephanie J. Albanes, Demetrius Fraumeni, Joseph F., Jr. Curtis, Rochelle E. de Gonzalez, Amy Berrington Morton, Lindsay M. TI Body Mass Index and Risk of Second Obesity-Associated Cancers After Colorectal Cancer: A Pooled Analysis of Prospective Cohort Studies SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article ID POSTMENOPAUSAL BREAST-CANCER; SUBSEQUENT PRIMARY CANCERS; IOWA WOMENS HEALTH; WEIGHT CHANGE; NATIONAL-INSTITUTES; COLON-CANCER; PHYSICAL-ACTIVITY; UNITED-STATES; SURVIVAL; DIAGNOSIS AB Purpose To determine whether prediagnostic body mass index (BMI) is associated with risk of second obesity-associated cancers in colorectal cancer (CRC) survivors, and whether CRC survivors have increased susceptibility to obesity-associated cancer compared with cancer-free individuals. Patients and Methods Incident first primary CRC cases (N = 11,598) were identified from five prospective cohort studies. We used Cox proportional hazards regression models to examine associations between baseline (prediagnostic) BMI and risk of second obesity-associated cancers (postmenopausal breast, kidney, pancreas, esophageal adenocarcinoma, endometrium) in CRC survivors, and compared associations to those for first obesity-associated cancers in the full cohort. Results Compared with survivors with normal prediagnostic BMI (18.5-24.9 kg/m(2)), those who were overweight (25-29.9 kg/m(2)) or obese (30 + kg/m(2)) had greater risk of a second obesity-associated cancer (n = 224; overweight hazard ratio [HR], 1.39; 95% CI, 1.01 to 1.92; obese HR, 1.47; 95% CI, 1.02 to 2.12; per 5-unit change in BMI HR, 1.12; 95% CI, 0.98 to 1.29). The magnitude of risk for developing a first primary obesity-associated cancer was similar (overweight HR, 1.18; 95% CI, 1.14 to 1.21; obese HR, 1.61; 95% CI, 1.56 to 1.66; per 5-unit change in BMI HR, 1.23; 95% CI, 1.21 to 1.24). Before diagnosis CRC patients were somewhat more likely than the overall cohort to be overweight (44% v 41%) or obese (25% v 21%). Conclusion CRC survivors who were overweight or obese before diagnosis had increased risk of second obesity-associated cancers compared with survivors with normal weight. The risks were similar in magnitude to those observed for first cancers in this population, suggesting increased prevalence of overweight or obesity, rather than increased susceptibility, may contribute to elevated second cancer risks in colorectal cancer survivors compared with the general population. These results support emphasis of existing weight guidelines for this high-risk group. (C) 2014 by American Society of Clinical Oncology C1 [Gibson, Todd M.; Park, Yikyung; Shiels, Meredith S.; Black, Amanda; Sampson, Joshua N.; Purdue, Mark P.; Freeman, Laura E. Beane; Andreotti, Gabriella; Weinstein, Stephanie J.; Albanes, Demetrius; Fraumeni, Joseph F., Jr.; Curtis, Rochelle E.; de Gonzalez, Amy Berrington; Morton, Lindsay M.] NCI, Bethesda, MD 20892 USA. [Robien, Kim] George Washington Univ, Milken Inst Sch Publ Hlth, Washington, DC USA. RP Gibson, TM (reprint author), St Jude Childrens Res Hosp, 262 Danny Thomas Pl,Mail Stop 735, Memphis, TN 38105 USA. EM todd.gibson@stjude.org RI Morton, Lindsay/B-5234-2015; Albanes, Demetrius/B-9749-2015; Purdue, Mark/C-9228-2016; OI Morton, Lindsay/0000-0001-9767-2310; Purdue, Mark/0000-0003-1177-3108; Park, Yikyung/0000-0002-6281-489X FU Intramural program of the National Cancer Institute; National Institute of Environmental Health Sciences [Z01-ES049030]; National Cancer Institute [Z01-CP010119, R01 CA39742] FX This research was funded in part by the Intramural program of the National Cancer Institute. The Agricultural Health Study was additionally supported by the National Institute of Environmental Health Sciences (Z01-ES049030) and National Cancer Institute (Z01-CP010119). The Iowa Women's Health Study was funded by National Cancer Institute grant R01 CA39742. NR 42 TC 12 Z9 12 U1 1 U2 14 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 10 PY 2014 VL 32 IS 35 BP 4004 EP U151 DI 10.1200/JCO.2014.56.8444 PG 10 WC Oncology SC Oncology GA AU9IK UT WOS:000345905100017 PM 25267739 ER PT J AU Mitchell, EM Lyles, RH Manatunga, AK Perkins, NJ Schisterman, EF AF Mitchell, Emily M. Lyles, Robert H. Manatunga, Amita K. Perkins, Neil J. Schisterman, Enrique F. TI A highly efficient design strategy for regression with outcome pooling SO STATISTICS IN MEDICINE LA English DT Article DE biomarkers; design; k-means clustering; pooling; regression analysis ID BIOMARKER DATA SUBJECT; PREVALENCE; MODELS; HIV AB The potential for research involving biospecimens can be hindered by the prohibitive cost of performing laboratory assays on individual samples. To mitigate this cost, strategies such as randomly selecting a portion of specimens for analysis or randomly pooling specimens prior to performing laboratory assays may be employed. These techniques, while effective in reducing cost, are often accompanied by a considerable loss of statistical efficiency. We propose a novel pooling strategy based on the k-means clustering algorithm to reduce laboratory costs while maintaining a high level of statistical efficiency when predictor variables are measured on all subjects, but the outcome of interest is assessed in pools. We perform simulations motivated by the BioCycle study to compare this k-means pooling strategy with current pooling and selection techniques under simple and multiple linear regression models. While all of the methods considered produce unbiased estimates and confidence intervals with appropriate coverage, pooling under k-means clustering provides the most precise estimates, closely approximating results from the full data and losing minimal precision as the total number of pools decreases. The benefits of k-means clustering evident in the simulation study are then applied to an analysis of the BioCycle dataset. In conclusion, when the number of lab tests is limited by budget, pooling specimens based on k-means clustering prior to performing lab assays can be an effective way to save money with minimal information loss in a regression setting. Copyright (C) 2014 JohnWiley & Sons, Ltd. C1 [Mitchell, Emily M.; Perkins, Neil J.; Schisterman, Enrique F.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Div Intramural Populat Hlth Res, Bethesda, MD 20892 USA. [Mitchell, Emily M.; Lyles, Robert H.; Manatunga, Amita K.] Emory Univ, Rollins Sch Publ Hlth, Dept Biostat & Bioinformat, Atlanta, GA 30322 USA. RP Mitchell, EM (reprint author), Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Div Intramural Populat Hlth Res, Bethesda, MD 20892 USA. EM emily.mitchell@nih.gov OI Perkins, Neil/0000-0002-6802-4733; Schisterman, Enrique/0000-0003-3757-641X FU National Institute of Nursing Research [1RC4NR012527-01]; National Institute of Environmental Health Sciences [5R01ES012458-07]; Intramural Research Program of the Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health; Long-Range Research Initiative of the American Chemistry Council; National Center for Advancing Translational Sciences of the National Institutes of Health [UL1TR000454] FX This research was supported by grants from the National Institute of Nursing Research (1RC4NR012527-01), the National Institute of Environmental Health Sciences (5R01ES012458-07), the Intramural Research Program of the Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, and by the Long-Range Research Initiative of the American Chemistry Council. Additional partial support from the National Center for Advancing Translational Sciences of the National Institutes of Health under award number UL1TR000454 is also acknowledged. NR 23 TC 5 Z9 5 U1 0 U2 4 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0277-6715 EI 1097-0258 J9 STAT MED JI Stat. Med. PD DEC 10 PY 2014 VL 33 IS 28 BP 5028 EP 5040 DI 10.1002/sim.6305 PG 13 WC Mathematical & Computational Biology; Public, Environmental & Occupational Health; Medical Informatics; Medicine, Research & Experimental; Statistics & Probability SC Mathematical & Computational Biology; Public, Environmental & Occupational Health; Medical Informatics; Research & Experimental Medicine; Mathematics GA AT5YU UT WOS:000345016700013 PM 25220822 ER PT J AU Woodard, GE Ji, Y Christopherson, GT Wolcott, KM Hall, DJ Jackson, WM Nesti, LJ AF Woodard, Geoffrey E. Ji, Youngmi Christopherson, Gregory T. Wolcott, Karen M. Hall, David J. Jackson, Wesley M. Nesti, Leon J. TI Characterization of Discrete Subpopulations of Progenitor Cells in Traumatic Human Extremity Wounds SO PLOS ONE LA English DT Article ID VASCULAR ENDOTHELIAL-CELLS; MUSCLE SATELLITE CELLS; STEM-CELLS; CEREBRAL VASOSPASM; INJURY; TISSUE; DIFFERENTIATION; MECHANISMS; EXPRESSION; CD34 AB Here we show that distinct subpopulations of cells exist within traumatic human extremity wounds, each having the ability to differentiate into multiple cells types in vitro. A crude cell suspension derived from traumatized muscle was positively sorted for CD29, CD31, CD34, CD56 or CD91. The cell suspension was also simultaneously negatively sorted for either CD45 or CD117 to exclude hematopoietic stem cells. These subpopulations varied in terms their total numbers and their abilities to grow, migrate, differentiate and secrete cytokines. While all five subpopulations demonstrated equal abilities to undergo osteogenesis, they were distinct in their ability to undergo adipogenesis and vascular endotheliogenesis. The most abundant subpopulations were CD29+ and CD34+, which overlapped significantly. The CD29+ and CD34+ cells had the greatest proliferative and migratory capacity while the CD56+ subpopulation produced the highest amounts of TGFSS1 and TGFSS2. When cultured under endothelial differentiation conditions the CD29+ and CD34+ cells expressed VE-cadherin, Tie2 and CD31, all markers of endothelial cells. These data indicate that while there are multiple cell types within traumatized muscle that have osteogenic differentiation capacity and may contribute to bone formation in post-traumatic heterotopic ossification (HO), the major contributory cell types are CD29+ and CD34+, which demonstrate endothelial progenitor cell characteristics. C1 [Woodard, Geoffrey E.; Jackson, Wesley M.; Nesti, Leon J.] Uniformed Serv Univ Hlth Sci, Dept Surg, Bethesda, MD 20814 USA. [Ji, Youngmi; Christopherson, Gregory T.; Hall, David J.; Nesti, Leon J.] NIAMSD, NIH, Bethesda, MD 20892 USA. [Wolcott, Karen M.] NCI, Lab Genome Integr, NIH, Bethesda, MD 20892 USA. [Nesti, Leon J.] Walter Reed Natl Mil Med Ctr, Dept Orthopaed Surg, Bethesda, MD USA. RP Woodard, GE (reprint author), Uniformed Serv Univ Hlth Sci, Dept Surg, Bethesda, MD 20814 USA. EM gew232000@gmail.com; leonnesti@gmail.com FU Military Amputee Research Program at Walter Reed Army Medical Center [P05-A011]; Comprehensive Neurosciences Program [CNP-2008-CR01]; Defense Medical Research and Development Program [D10_1_AR_J5_920]; NIH Intramural Research Program [Z01 AR41131] FX Support was provided by the Military Amputee Research Program at Walter Reed Army Medical Center (P05-A011), the Comprehensive Neurosciences Program (CNP-2008-CR01), the Defense Medical Research and Development Program (D10_1_AR_J5_920) and the NIH Intramural Research Program (Z01 AR41131). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 56 TC 4 Z9 5 U1 1 U2 4 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA SN 1932-6203 J9 PLOS ONE JI PLoS One PD DEC 9 PY 2014 VL 9 IS 12 AR e114318 DI 10.1371/journal.pone.0114318 PG 20 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA AY3YM UT WOS:000347515300028 PM 25490403 ER PT J AU Tran, CH Sugimoto, JD Pulliam, JRC Ryan, KA Myers, PD Castleman, JB Doty, R Johnson, J Stringfellow, J Kovacevich, N Brew, J Cheung, LL Caron, B Lipori, G Harle, CA Alexander, C Yang, Y Longini, IM Halloran, ME Morris, JG Small, PA AF Tran, Cuc H. Sugimoto, Jonathan D. Pulliam, Juliet R. C. Ryan, Kathleen A. Myers, Paul D. Castleman, Joan B. Doty, Randell Johnson, Jackie Stringfellow, Jim Kovacevich, Nadia Brew, Joe Cheung, Lai Ling Caron, Brad Lipori, Gloria Harle, Christopher A. Alexander, Charles Yang, Yang Longini, Ira M., Jr. Halloran, M. Elizabeth Morris, J. Glenn, Jr. Small, Parker A., Jr. TI School-Located Influenza Vaccination Reduces Community Risk for Influenza and Influenza-Like Illness Emergency Care Visits SO PLOS ONE LA English DT Article ID UNITED-STATES; PANDEMIC INFLUENZA; SCHOOLCHILDREN; COVERAGE; CHILDREN; SEASON; TECUMSEH; OUTBREAK AB Background: School-located influenza vaccination (SLIV) programs can substantially enhance the sub-optimal coverage achieved under existing delivery strategies. Randomized SLIV trials have shown these programs reduce laboratory-confirmed influenza among both vaccinated and unvaccinated children. This work explores the effectiveness of a SLIV program in reducing the community risk of influenza and influenza-like illness (ILI) associated emergency care visits. Methods: For the 2011/12 and 2012/13 influenza seasons, we estimated age-group specific attack rates (AR) for ILI from routine surveillance and census data. Age-group specific SLIV program effectiveness was estimated as one minus the AR ratio for Alachua County versus two comparison regions: the 12 county region surrounding Alachua County, and all non-Alachua counties in Florida. Results: Vaccination of,50% of 5-17 year-olds in Alachua reduced their risk of ILI-associated visits, compared to the rest of Florida, by 79% (95% confidence interval: 70, 85) in 2011/12 and 71% (63, 77) in 2012/13. The greatest indirect effectiveness was observed among 0-4 year-olds, reducing AR by 89% (84, 93) in 2011/12 and 84% (79, 88) in 2012/13. Among all non-school age residents, the estimated indirect effectiveness was 60% (54, 65) and 36% (31, 41) for 2011/12 and 2012/13. The overall effectiveness among all age-groups was 65% (61, 70) and 46% (42, 50) for 2011/12 and 2012/13. Conclusion: Wider implementation of SLIV programs can significantly reduce the influenza-associated public health burden in communities. C1 [Tran, Cuc H.] Univ Florida, Coll Publ Hlth & Hlth Profess, Dept Environm & Global Hlth, Gainesville, FL USA. [Tran, Cuc H.; Sugimoto, Jonathan D.; Pulliam, Juliet R. C.; Ryan, Kathleen A.; Cheung, Lai Ling; Yang, Yang; Longini, Ira M., Jr.; Morris, J. Glenn, Jr.; Small, Parker A., Jr.] Univ Florida, Emerging Pathogens Inst, Gainesville, FL 32611 USA. [Tran, Cuc H.; Harle, Christopher A.] Univ Florida, Clin Translat Sci Inst, Gainesville, FL USA. [Sugimoto, Jonathan D.; Brew, Joe] Univ Florida, Dept Epidemiol, Coll Publ Hlth & Hlth Profess, Gainesville, FL USA. [Sugimoto, Jonathan D.; Brew, Joe] Univ Florida, Coll Med, Dept Epidemiol, Gainesville, FL USA. [Sugimoto, Jonathan D.; Halloran, M. Elizabeth] Fred Hutchinson Canc Res Ctr, Vaccine & Infect Dis Div, Seattle, WA 98104 USA. [Pulliam, Juliet R. C.; Harle, Christopher A.] Univ Florida, Coll Liberal Arts & Sci, Dept Biol, Gainesville, FL USA. [Pulliam, Juliet R. C.] NIH, Fogarty Int Ctr, Bethesda, MD 20892 USA. [Ryan, Kathleen A.; Small, Parker A., Jr.] Univ Florida, Coll Med, Dept Pediat, Gainesville, FL USA. [Myers, Paul D.; Kovacevich, Nadia; Brew, Joe; Caron, Brad] Florida Dept Hlth Alachua Cty, Gainesville, FL USA. [Castleman, Joan B.] Univ Florida, Coll Nursing, Gainesville, FL 32611 USA. [Doty, Randell] Univ Florida, Coll Pharm, Gainesville, FL USA. [Johnson, Jackie] Alachua Cty Publ Sch, Gainesville, FL USA. [Stringfellow, Jim] Partnership Strong Families, Gainesville, FL USA. [Lipori, Gloria] Univ Florida Hlth Integrated Data Repository, UF Hlth, Gainesville, FL USA. [Harle, Christopher A.] Univ Florida, Coll Publ Hlth & Hlth Profess, Dept Hlth Serv Res Management & Policy, Gainesville, FL USA. [Alexander, Charles] Florida Dept Hlth, Tallahassee, FL USA. [Yang, Yang; Longini, Ira M., Jr.] Univ Florida, Coll Publ Hlth & Hlth Profess, Dept Biostat, Gainesville, FL USA. [Yang, Yang; Longini, Ira M., Jr.] Univ Florida, Coll Med, Dept Biostat, Gainesville, FL USA. [Halloran, M. Elizabeth] Univ Washington, Dept Biostat, Seattle, WA 98195 USA. [Morris, J. Glenn, Jr.] Univ Florida, Coll Med, Dept Med, Gainesville, FL USA. [Small, Parker A., Jr.] Univ Florida, Coll Med, Dept Pathol, Gainesville, FL USA. RP Morris, JG (reprint author), Univ Florida, Emerging Pathogens Inst, Gainesville, FL 32611 USA. EM JGMorris@epi.ufl.edu RI Pulliam, Juliet/A-6516-2008; OI Pulliam, Juliet/0000-0003-3314-8223; Brew, Joe/0000-0002-4119-0117 FU University of Florida Emerging Pathogens Institute; National Institutes of Health [NIH R37 AI032042, NIH U01 GM070749, NIH U54 GM111274, UL1 TR000064, TL1TR000066, KL2TR000065]; Alachua County Board of Commissioners Community Health Offering Innovative Care & Educational Services (CHOICES) FX This work was supported by internal funding from the University of Florida Emerging Pathogens Institute and funding from the National Institutes of Health (NIH R37 AI032042, NIH U01 GM070749, NIH U54 GM111274 to J.D.S., Y.Y, I.M.L., M.E.H), (UL1 TR000064 & TL1TR000066 to C.H.T), (UL1 TR000064 & KL2TR000065 to C.A.H). The Alachua County School-located Influenza Vaccination program (Florida Department of Health in Alachua County) is supported by the Alachua County Board of Commissioners Community Health Offering Innovative Care & Educational Services (CHOICES), and vaccine reimbursement from private health insurance and Medicaid. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 33 TC 5 Z9 5 U1 2 U2 12 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 9 PY 2014 VL 9 IS 12 AR UNSP e114479 DI 10.1371/journal.pone.0114479 PG 17 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA AY3YM UT WOS:000347515300043 PM 25489850 ER PT J AU Lai, GY Weinstein, SJ Taylor, PR McGlynn, KA Virtamo, J Gail, MH Albanes, D Freedman, ND AF Lai, G. Y. Weinstein, S. J. Taylor, P. R. McGlynn, K. A. Virtamo, J. Gail, M. H. Albanes, D. Freedman, N. D. TI Effects of alpha-tocopherol and beta-carotene supplementation on liver cancer incidence and chronic liver disease mortality in the ATBC study SO BRITISH JOURNAL OF CANCER LA English DT Article DE randomised trial; vitamin supplement; liver cancer; chronic liver disease ID HEPATOCELLULAR-CARCINOMA; NONALCOHOLIC STEATOHEPATITIS; SERUM RETINOL; VITAMIN-E; RISK; PIOGLITAZONE; CIRRHOSIS; TRIAL; LEVEL AB Background: Recent data suggest the possible benefits of alpha-tocopherol and beta-carotene supplementation on liver cancer and chronic liver disease (CLD), but the long-term trial data are limited. Methods: We evaluated the efficacy of supplemental 50 mg day(-1) alpha-tocopherol and 20 mg day(-1) beta-carotene on incident liver cancer and CLD mortality in a randomised trial of 29 105 Finnish male smokers, who received supplementation for 5-8 years and were followed for 16 additional years for outcomes. Results: Supplemental alpha-tocopherol, beta-carotene, or both, relative to placebo, did not reduce the risk of liver cancer or CLD, either overall, during the intervention or during the post-intervention period. Conclusions: Long-term supplemental alpha-tocopherol or beta-carotene had no effect on liver cancer or CLD mortality over 24 years of follow-up. C1 [Lai, G. Y.] NCI, Cancer Prevent Fellowship Program, Bethesda, MD 20892 USA. [Lai, G. Y.; Weinstein, S. J.; Albanes, D.; Freedman, N. D.] NCI, Nutr Epidemiol Branch, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. [Taylor, P. R.] NCI, Genet Epidemiol Branch, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. [McGlynn, K. A.] NCI, Hormonal & Reprod Epidemiol Branch, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. [Virtamo, J.] Natl Inst Hlth & Welf, Dept Chron Dis Prevent, FI-00271 Helsinki, Finland. [Gail, M. H.] NCI, Biostat Branch, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. RP Lai, GY (reprint author), NCI, Cancer Prevent Fellowship Program, 9609 Med Ctr Dr,Rm 2W136,MSC 9712, Bethesda, MD 20892 USA. EM laigy@mail.nih.gov RI Albanes, Demetrius/B-9749-2015; Freedman, Neal/B-9741-2015 OI Freedman, Neal/0000-0003-0074-1098 FU Intramural Research Program, Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Department of Health and Human Services; US Public Health Service [N01-CN-45165, N01-RC-45035, N01-RC-37004] FX We thank all individuals for their participation in this study. This research was supported by the Intramural Research Program, Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Department of Health and Human Services and US Public Health Service contracts (N01-CN-45165, N01-RC-45035, and N01-RC-37004). The ATBC Study was registered with clinicaltrials.gov (#NCT00342992). NR 22 TC 4 Z9 4 U1 0 U2 3 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0007-0920 EI 1532-1827 J9 BRIT J CANCER JI Br. J. Cancer PD DEC 9 PY 2014 VL 111 IS 12 BP 2220 EP 2223 DI 10.1038/bjc.2014.514 PG 4 WC Oncology SC Oncology GA AW4JJ UT WOS:000346247000003 PM 25314069 ER PT J AU Roshandel, G Merat, S Sotoudeh, M Khoshnia, M Poustchi, H Lao-Sirieix, P Malhotra, S O'Donovan, M Etemadi, A Nickmanesh, A Pourshams, A Norouzi, A Debiram, I Semnani, S Abnet, CC Dawsey, SM Fitzgerald, RC Malekzadeh, R AF Roshandel, G. Merat, S. Sotoudeh, M. Khoshnia, M. Poustchi, H. Lao-Sirieix, P. Malhotra, S. O'Donovan, M. Etemadi, A. Nickmanesh, A. Pourshams, A. Norouzi, A. Debiram, I. Semnani, S. Abnet, C. C. Dawsey, S. M. Fitzgerald, R. C. Malekzadeh, R. TI Pilot study of cytological testing for oesophageal squamous cell dysplasia in a high-risk area in Northern Iran SO BRITISH JOURNAL OF CANCER LA English DT Article DE oesophageal squamous cell carcinoma; screening; cytological examination; p53; Northern Iran ID ASYMPTOMATIC ADULTS; CARCINOMA; CANCER; CHINA; LINXIAN; POPULATION; NEOPLASIA; LESIONS; ADENOCARCINOMA; SAMPLERS AB Background: Oesophageal squamous cell carcinoma (ESCC) is a fatal disease with 5-year survival rates of <5% in Northern Iran. Oesophageal squamous dysplasia (ESD) is the precursor histologic lesion of ESCC. This pilot study was conducted to assess the feasibility, safety, and acceptability of non-endoscopic cytological examination of the oesophagus and to provide initial data on the accuracy of cytological atypia for identifying patients with ESD in this very-high-risk area. Methods: Randomly selected asymptomatic participants of the Golestan Cohort Study were recruited. A cytological specimen was taken using a capsule sponge device and evaluated for atypical cells. Sections of the cytological specimen were also stained for p53 protein. Patient acceptability was assessed using a visual analogue scale. The cytological diagnosis was compared with a chromoendoscopic examination using Lugol's solution. Results: Three hundred and forty-four subjects (43% male, mean (s.d.) age 55.6 (7.9) years) were referred to the study clinic. Three hundred and twelve met eligibility criteria and consented, of which 301 subjects (96.5%) completed both cytological and endoscopic examinations. There were no complications. Most of the participants (279; 92.7%) were satisfied with the examination. The sensitivity and specificity of the cytological examination for identifying subjects with high-grade ESD were 100 and 97%, respectively. We found an accuracy of 100% (95% CI = 99-100%) for a combination of cytological examination and p53 staining to detect high-grade ESD. Conclusions: The capsule sponge methodology seems to be a feasible, safe, and acceptable method for diagnosing precancerous lesions of the oesophagus in this population, with promising initial accuracy data for the detection of high-grade ESD. C1 [Roshandel, G.; Merat, S.; Sotoudeh, M.; Poustchi, H.; Etemadi, A.; Nickmanesh, A.; Pourshams, A.; Malekzadeh, R.] Univ Tehran Med Sci, Shariati Hosp, Digest Dis Res Inst, Digest Oncol Res Ctr, Tehran 1411713135, Iran. [Roshandel, G.; Khoshnia, M.; Norouzi, A.; Semnani, S.] Golestan Univ Med Sci, Golestan Res Ctr Gastroenterol & Hepatol, Gorgan 4917774979, Iran. [Lao-Sirieix, P.; Malhotra, S.; O'Donovan, M.; Fitzgerald, R. C.] Univ Cambridge, MRC Canc Cell, Hutchison MRC Res Ctr, Cambridge CB2 0XZ, England. [Etemadi, A.; Abnet, C. C.; Dawsey, S. M.] NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20895 USA. RP Malekzadeh, R (reprint author), Univ Tehran Med Sci, Shariati Hosp, Digest Dis Res Inst, Digest Oncol Res Ctr, Tehran 1411713135, Iran. EM dr.reza.malekzadeh@gmail.com RI Abnet, Christian/C-4111-2015; Etemadi, Arash/C-1386-2016; Norouzi, Alireza/L-6872-2016; Semnani, Shahryar/N-2270-2016; Roshandel, gholamreza/N-2260-2016; Khoshnia, Masoud/P-5665-2016; OI Abnet, Christian/0000-0002-3008-7843; Etemadi, Arash/0000-0002-3458-1072; Norouzi, Alireza/0000-0003-4227-7350; Semnani, Shahryar/0000-0002-8768-6142; Roshandel, gholamreza/0000-0002-5494-0722; Khoshnia, Masoud/0000-0001-7352-8058; Malekzadeh, Reza/0000-0003-1043-3814 FU Digestive Disease Research Institute (DDRI); Golestan Research Center of Gastroenterology and Hepatology (GRCGH); Intramural Research Program of the National Cancer Institute, NIH FX We would like to thank Miss Kor, Mrs Ghasemi-Kebria, Mrs Noorbakhsh, Dr Sharifi, Dr Khalilipour, Dr Abaie, Mr Yolmeh, Mr Ataie, Mrs Nasi and Mrs Mohammadi for their valuable work in data collection and sample processing. This study was supported by the Digestive Disease Research Institute (DDRI) affiliated with Tehran University of Medical Sciences (TUMS) as a thesis for obtaining a PhD degree; the Golestan Research Center of Gastroenterology and Hepatology (GRCGH) affiliated with Golestan University of Medical Sciences (GOUMS); and in part by the Intramural Research Program of the National Cancer Institute, NIH. NR 41 TC 4 Z9 4 U1 0 U2 5 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0007-0920 EI 1532-1827 J9 BRIT J CANCER JI Br. J. Cancer PD DEC 9 PY 2014 VL 111 IS 12 BP 2235 EP 2241 DI 10.1038/bjc.2014.506 PG 7 WC Oncology SC Oncology GA AW4JJ UT WOS:000346247000006 PM 25247319 ER PT J AU Koczywas, M Frankel, PH Synold, TW Lenz, HJ Mortimer, JE El-Khoueiry, AB Gandara, DR Cristea, MC Chung, VM Lim, D Reckamp, KL Lau, DH Doyle, LA Ruel, C Carroll, MI Newman, EM AF Koczywas, M. Frankel, P. H. Synold, T. W. Lenz, H-J Mortimer, J. E. El-Khoueiry, A. B. Gandara, D. R. Cristea, M. C. Chung, V. M. Lim, D. Reckamp, K. L. Lau, D. H. Doyle, L. A. Ruel, C. Carroll, M. I. Newman, E. M. TI Phase I study of the halichondrin B analogue eribulin mesylate in combination with cisplatin in advanced solid tumors SO BRITISH JOURNAL OF CANCER LA English DT Article DE eribulin mesylate (E7389); cisplatin; advanced solid tumours ID E7389; MECHANISM; TUBULIN; BINDING AB Background: Eribulin mesylate is a synthetic macrocyclic ketone analogue of Halichondrin B that has demonstrated high antitumor activity in preclinical and clinical settings. This phase I study aimed to determine the maximum tolerated dose (MTD), dose-limiting toxicities (DLTs), and pharmacokinetics in combination with cisplatin (CP) in patients with advanced solid tumours. Methods: Thirty-six patients with advanced solid tumours received eribulin mesylate 0.7-1.4 mg m(-2) and CP 60-75 mg m(-2). Eribulin mesylate was administered on days 1, 8, and 15 in combination with CP day 1 every 28-day cycle. The protocol was amended after dose level 4 (eribulin mesylate 1.4 mg m(-2), CP 60 mg m(-2)) when it was not feasible to administer eribulin mesylate on day 15 because of neutropenia; the treatment schedule was changed to eribulin mesylate on days 1 and 8 and CP on day 1 every 21 days. Results: On the 28-day schedule, three patients had DLT during the first cycle: grade (G) 4 febrile neutropenia (1.0 mg m(-2), 60 mg m(-2)); G 3 anorexia/fatigue/hypokalemia (1.2 mg m(-2), 60 mg m(-2)); and G 3 stomatitis/nausea/vomiting/fatigue (1.4 mg m(-2), 60 mg m(-2)). On the 21-day schedule, three patients had DLT during the first cycle: G 3 hypokalemia/hyponatremia (1.4 mg m(-2), 60 mg m(-2)); G 4 mucositis (1.4 mg m(-2), 60 mg m(-2)); and G 3 hypokalemia (1.2 mg m(-2), 75 mg m(-2)). The MTD and recommended phase II dose was determined as eribulin mesylate 1.2 mg m(-2) (days 1, 8) and CP 75 mg m(-2) (day 1), on a 21-day cycle. Two patients had unconfirmed partial responses (PR) (pancreatic and breast cancers) and two had PR (oesophageal and bladder cancers). Conclusions: On the 21-day cycle, eribulin mesylate 1.2 mg m(-2), administered on days 1 and 8, in combination with CP 75 mg m(-2), administered on day 1 is well tolerated and showed preliminary anticancer activity. C1 [Koczywas, M.; Mortimer, J. E.; Cristea, M. C.; Chung, V. M.; Lim, D.; Reckamp, K. L.] City Hope Natl Med Ctr, Dept Med Oncol, Duarte, CA 91010 USA. [Frankel, P. H.; Ruel, C.] City Hope Natl Med Ctr, Dept Informat Sci, Duarte, CA USA. [Synold, T. W.; Newman, E. M.] City Hope Natl Med Ctr, Natl Med Ctr, Dept Mol Pharmacol, Duarte, CA USA. [Lenz, H-J; El-Khoueiry, A. B.] Univ So Calif, Kenneth Norris Jr Comprehens Canc Ctr, Los Angeles, CA 90033 USA. [Gandara, D. R.; Lau, D. H.] Univ Calif Davis, Med Ctr, Ctr Comprehens Canc, Sacramento, CA 95817 USA. [Doyle, L. A.] NCI, Rockville, MD USA. [Carroll, M. I.] City Hope Natl Med Ctr, Dep Res RN, Duarte, CA USA. RP Koczywas, M (reprint author), City Hope Natl Med Ctr, Dept Med Oncol, Duarte, CA 91010 USA. EM mkoczywas@coh.org OI Reckamp, Karen/0000-0002-9213-0325 FU National Cancer Institute Cancer Therapy Evaluation Program; National Cancer Institute of the National Institutes of Health [U01CA062505/UM1CA186717, P30CA33572, P30 CA014089, P30 CA93373] FX A California Cancer Consortium trial sponsored by the National Cancer Institute Cancer Therapy Evaluation Program. Research reported in this publication was supported by the National Cancer Institute of the National Institutes of Health under award numbers U01CA062505/UM1CA186717 (City of Hope), P30CA33572 (City of Hope, including work performed in the Analytical Pharmacology Core), P30 CA014089 (University of Southern California) and P30 CA93373 (University of California, Davis). The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. NR 20 TC 4 Z9 4 U1 0 U2 5 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0007-0920 EI 1532-1827 J9 BRIT J CANCER JI Br. J. Cancer PD DEC 9 PY 2014 VL 111 IS 12 BP 2268 EP 2274 DI 10.1038/bjc.2014.554 PG 7 WC Oncology SC Oncology GA AW4JJ UT WOS:000346247000011 PM 25349975 ER PT J AU Heckman, MG Schottlaender, L Soto-Ortolaza, AI Diehl, NN Rayaprolu, S Ogaki, K Fujioka, S Murray, ME Cheshire, WP Uitti, RJ Wszolek, ZK Farrer, MJ Sailer, A Singleton, AB Chinnery, PF Keogh, MJ Gentleman, SM Holton, JL Aoife, K Mann, DMA Al-Sarraj, S Troakes, C Dickson, DW Houlden, H Ross, OA AF Heckman, Michael G. Schottlaender, Lucia Soto-Ortolaza, Alexandra I. Diehl, Nancy N. Rayaprolu, Sruti Ogaki, Kotaro Fujioka, Shinsuke Murray, Melissa E. Cheshire, William P. Uitti, Ryan J. Wszolek, Zbigniew K. Farrer, Matthew J. Sailer, Anna Singleton, Andrew B. Chinnery, Patrick F. Keogh, Michael J. Gentleman, Steve M. Holton, Janice L. Aoife, Kiely Mann, David M. A. Al-Sarraj, Safa Troakes, Claire Dickson, Dennis W. Houlden, Henry Ross, Owen A. TI LRRK2 exonic variants and risk of multiple system atrophy SO NEUROLOGY LA English DT Article ID SNCA VARIANTS; ASSOCIATION AB Objective:The aim of this study was to evaluate the association between common exonic variants in the leucine-rich repeat kinase 2 (LRRK2) gene and risk of multiple system atrophy (MSA).Methods:One series from the United States (92 patients with pathologically confirmed MSA, 416 controls) and a second series from the United Kingdom (85 patients with pathologically confirmed MSA, 352 controls) were included in this case-control study. We supplemented these data with those of 53 patients from the United States with clinically probable or possible MSA. Seventeen common LRRK2 exonic variants were genotyped and assessed for association with MSA.Results:In the combined series of 177 patients with pathologically confirmed MSA and 768 controls, there was a significant association between LRRK2 p.M2397T and MSA (odds ratio [OR] = 0.60, p = 0.002). This protective effect was observed more strongly in the US series (OR = 0.46, p = 0.0008) than the UK series (OR = 0.82, p = 0.41). We observed other noteworthy associations with MSA for p.G1624G (OR = 0.63, p = 0.006) and p.N2081D (OR = 0.15, p = 0.010). The p.G1624G-M2397T haplotype was significantly associated with MSA in the US series (p < 0.0001) and combined series (p = 0.003) but not the UK series (p = 0.67). Results were consistent when additionally including the US patients with clinical MSA, where the strongest single-variant association was again observed for p.M2397T (OR = 0.59, p = 0.0005).Conclusions:These findings provide evidence that LRRK2 exonic variants may contribute to susceptibility to MSA. Validation in other series and meta-analytic studies will be important. C1 [Heckman, Michael G.; Diehl, Nancy N.] Mayo Clin, Biostat Sect, Jacksonville, FL 32224 USA. [Soto-Ortolaza, Alexandra I.; Rayaprolu, Sruti; Ogaki, Kotaro; Murray, Melissa E.; Dickson, Dennis W.; Ross, Owen A.] Mayo Clin, Dept Neurosci, Jacksonville, FL 32224 USA. [Fujioka, Shinsuke; Cheshire, William P.; Uitti, Ryan J.; Wszolek, Zbigniew K.] Mayo Clin, Dept Neurol, Jacksonville, FL 32224 USA. [Schottlaender, Lucia; Sailer, Anna; Houlden, Henry] Inst Neurol, Dept Mol Neurosci, London WC1N 3BG, England. [Schottlaender, Lucia; Sailer, Anna; Houlden, Henry] Natl Hosp Neurol & Neurosurg, London WC1N 3BG, England. [Farrer, Matthew J.] Univ British Columbia, Dept Med Genet, Vancouver, BC, Canada. [Singleton, Andrew B.] NIA, Neurogenet Lab, Bethesda, MD 20892 USA. [Chinnery, Patrick F.; Keogh, Michael J.] Newcastle Univ, Inst Med Genet, Newcastle Upon Tyne NE1 7RU, Tyne & Wear, England. [Gentleman, Steve M.] Univ London Imperial Coll Sci Technol & Med, Dept Med, Neuropathol Unit, London SW7 2AZ, England. [Holton, Janice L.; Aoife, Kiely] UCL, UCL Inst Neurol, Dept Mol Neurosci, Queen Sq Brain Bank Neurol Disorders, London WC1E 6BT, England. [Mann, David M. A.] Univ Manchester, Salford Royal Hosp, Inst Brain Behav & Mental Hlth, Clin & Cognit Sci Res Grp,Fac Med & Human Sci, Salford, Lancs, England. [Al-Sarraj, Safa; Troakes, Claire] Kings Coll London, MRC London Neurodegenerat Dis Brain Bank, London WC2R 2LS, England. RP Heckman, MG (reprint author), Mayo Clin, Biostat Sect, Jacksonville, FL 32224 USA. EM heckman.michael@mayo.edu RI Murray, Melissa/C-2763-2015; Singleton, Andrew/C-3010-2009; Troakes, Claire/K-4346-2015; Houlden, Henry/C-1532-2008; OI Murray, Melissa/0000-0001-7379-2545; Houlden, Henry/0000-0002-2866-7777; Cheshire, William/0000-0002-6364-5362 FU NIH/National Institute of Neurological Disorders and Stroke [P50 NS072187]; National Institute of Neurological Disorders and Stroke [R01 NS078086]; Michael J. Fox Foundation for Parkinson's Research; Canada Excellence Research Chairs program; Dr. Donald Rix BC Leadership Chair; Cundill Foundation; Reta Lila Weston Institute for Neurological Studies; Multiple System Atrophy Trust; Department of Health's NIHR Biomedical Research Centres funding scheme FX R.J.U., O.A.R., Z.K.W., and D.W.D. are partially supported by the NIH/National Institute of Neurological Disorders and Stroke P50 NS072187. O.A.R. is supported by the National Institute of Neurological Disorders and Stroke R01 NS078086. M.J.F. and O.A.R. are supported by the Michael J. Fox Foundation for Parkinson's Research. Z.K.W. is also partially supported by the Michael J. Fox Foundation for Parkinson's Research, and the gift from Carl Edward Bolch, Jr., and Susan Bass Bolch. M.J.F. is also supported by the Canada Excellence Research Chairs program, the Dr. Donald Rix BC Leadership Chair, and the Cundill Foundation. J.H. is supported by the Reta Lila Weston Institute for Neurological Studies and the Multiple System Atrophy Trust. Part of this work was undertaken at UCLH/UCL who received a proportion of funding from the Department of Health's NIHR Biomedical Research Centres funding scheme. NR 11 TC 9 Z9 9 U1 1 U2 4 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0028-3878 EI 1526-632X J9 NEUROLOGY JI Neurology PD DEC 9 PY 2014 VL 83 IS 24 BP 2256 EP 2261 DI 10.1212/WNL.0000000000001078 PG 6 WC Clinical Neurology SC Neurosciences & Neurology GA AW1SK UT WOS:000346070000015 PM 25378673 ER PT J AU Stone, J Hallett, M Carson, A Bergen, D Shakir, R AF Stone, Jon Hallett, Mark Carson, Alan Bergen, Donna Shakir, Raad TI Functional disorders in the Neurology section of ICD-11 A landmark opportunity SO NEUROLOGY LA English DT Editorial Material AB Functional disorders are one of the most common diagnoses in neurologic practice, but this is not reflected in current classification systems. The 11th revision of the World Health Organization's International Classification of Diseases (ICD-11) in 2017 offers an opportunity for these disorders to appear within both neurologic and psychiatric categories for the first time. We discuss the rationale for this proposal and highlight the potential benefits for health professionals and patients. C1 [Stone, Jon] Univ Edinburgh, Western Gen Hosp, Dept Clin Neurosci, Edinburgh, Midlothian, Scotland. [Carson, Alan] Univ Edinburgh, Dept Psychiat, Western Gen Hosp, Edinburgh EH8 9YL, Midlothian, Scotland. [Hallett, Mark] NINDS, Human Motor Control Sect, Med Neurol Branch, NIH, Bethesda, MD 20892 USA. [Bergen, Donna] Rush Univ, Med Ctr, Dept Neurol Sci, Chicago, IL 60612 USA. [Shakir, Raad] Charing Cross Hosp, Imperial Coll Healthcare, London, England. RP Stone, J (reprint author), Univ Edinburgh, Western Gen Hosp, Dept Clin Neurosci, Edinburgh, Midlothian, Scotland. EM Jon.Stone@ed.ac.uk OI Stone, Jon/0000-0001-9829-8092 NR 5 TC 3 Z9 3 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 0028-3878 EI 1526-632X J9 NEUROLOGY JI Neurology PD DEC 9 PY 2014 VL 83 IS 24 BP 2299 EP 2301 DI 10.1212/WNL.0000000000001063 PG 3 WC Clinical Neurology SC Neurosciences & Neurology GA AW1SK UT WOS:000346070000021 PM 25488992 ER PT J AU Baskaran, S Carlson, LA Stjepanovic, G Young, LN Kim, DJ Grob, P Stanley, RE Nogales, E Hurley, JH AF Baskaran, Sulochanadevi Carlson, Lars-Anders Stjepanovic, Goran Young, Lindsey N. Kim, Do Jin Grob, Patricia Stanley, Robin E. Nogales, Eva Hurley, James H. TI Architecture and Dynamics of the Autophagic Phosphatidylinositol 3-Kinase Complex SO ELIFE LA English DT Article ID ELECTRON-MICROSCOPY; CRYSTAL-STRUCTURE; PROTEIN-KINASE; BECLIN 1; LIPID KINASE; VPS34; SYSTEM; BIOGENESIS; ATG14L; DOMAIN AB The class III phosphatidylinositol 3-kinase complex I (PI3KC3-C1) that functions in early autophagy consists of the lipid kinase VPS34, the scaffolding protein VPS15, the tumor suppressor BECN1, and the autophagy-specific subunit ATG14. The structure of the ATG14-containing PI3KC3-C1 was determined by single-particle EM, revealing a V-shaped architecture. All of the ordered domains of VPS34, VPS15, and BECN1 were mapped by MBP tagging. The dynamics of the complex were defined using hydrogen-deuterium exchange, revealing a novel 20-residue ordered region C-terminal to the VPS34 C2 domain. VPS15 organizes the complex and serves as a bridge between VPS34 and the ATG14: BECN1 subcomplex. Dynamic transitions occur in which the lipid kinase domain is ejected from the complex and VPS15 pivots at the base of the V. The N-terminus of BECN1, the target for signaling inputs that regulate PI3KC3 activity, resides near the pivot point. These observations provide a framework for understanding the allosteric regulation of lipid kinase activity. C1 [Baskaran, Sulochanadevi; Carlson, Lars-Anders; Stjepanovic, Goran; Young, Lindsey N.; Kim, Do Jin; Grob, Patricia; Nogales, Eva; Hurley, James H.] Univ Calif Berkeley, Dept Mol & Cell Biol, Berkeley, CA 94720 USA. [Baskaran, Sulochanadevi; Carlson, Lars-Anders; Stjepanovic, Goran; Young, Lindsey N.; Kim, Do Jin; Grob, Patricia; Nogales, Eva; Hurley, James H.] Univ Calif Berkeley, Calif Inst Quantitat Biosci, Berkeley, CA 94720 USA. [Grob, Patricia; Nogales, Eva] Univ Calif Berkeley, Howard Hughes Med Inst, Berkeley, CA 94720 USA. [Nogales, Eva; Hurley, James H.] Univ Calif Berkeley, Lawrence Berkeley Natl Lab, Div Life Sci, Berkeley, CA 94720 USA. [Stanley, Robin E.] Natl Inst Diabet & Digest & Kidney Dis, Mol Biol Lab, NIH, Bethesda, MD 20892 USA. RP Nogales, E (reprint author), Univ Calif Berkeley, Dept Mol & Cell Biol, 229 Stanley Hall, Berkeley, CA 94720 USA. EM enogales@lbl.gov; jimhurley@berkeley.edu RI Stjepanovic, Goran/A-7902-2010 OI Stjepanovic, Goran/0000-0002-4841-9949 FU National Institutes of Health [GM111730]; Damon Runyon Cancer Research Fellowship; L'Oreal USA Women in Science Fellowship; Human Frontiers Science Program [LT001037/2011-L] FX This work was supported by National Institutes of Health grant GM111730 (J.H.H.). R. E. S. was supported by a Damon Runyon Cancer Research Fellowship and a L'Oreal USA Women in Science Fellowship. L.-A. C was supported by a Long-Term Fellowship from the Human Frontiers Science Program (LT001037/2011-L). We thank David Taylor for assistance with the tilt pair validation. E.N. is a Howard Hughes Medical Institute Investigator. NR 60 TC 29 Z9 30 U1 2 U2 4 PU ELIFE SCIENCES PUBLICATIONS LTD PI CAMBRIDGE PA SHERATON HOUSE, CASTLE PARK, CAMBRIDGE, CB3 0AX, ENGLAND SN 2050-084X J9 ELIFE JI eLife PD DEC 9 PY 2014 VL 3 AR e05115 DI 10.7554/eLife.05115 PG 36 WC Biology SC Life Sciences & Biomedicine - Other Topics GA AW3FB UT WOS:000346170300002 ER PT J AU Adamus, G Chew, EY Ferris, FL Klein, ML AF Adamus, Grazyna Chew, Emily Y. Ferris, Frederick L. Klein, Michael L. TI Prevalence of anti-retinal autoantibodies in different stages of Age-related macular degeneration SO BMC OPHTHALMOLOGY LA English DT Article DE Age-related macular degeneration; AREDS; Autoantibodies; Enolase; Antibody signature; Biomarker; Retina; Macula; Smoking; Arthritis ID CANCER-ASSOCIATED RETINOPATHY; PIGMENT EPITHELIAL-CELLS; COMPLEMENT FACTOR-H; ALPHA-ENOLASE; RHEUMATOID-ARTHRITIS; AUTOIMMUNE RETINOPATHY; CIGARETTE-SMOKING; RISK-FACTORS; INFLAMMATION; ANTIBODIES AB Background: Age-related macular degeneration (AMD) is the leading cause of central vision loss in older adults. Anti-retinal autoantibodies (AAbs) have been found in individuals with AMD. The goal of the study was to determine the AAb specificity in different stages of AMD, and determine whether there is a prevalent AAb signature. Methods: Sera of 134 participants in the Age-related Eye Disease Study were analyzed for anti-retinal AAbs by western blotting. The subjects were classified by diagnostic subgroups based upon their clinical classification: No AMD, Intermediate AMD, and Late AMD -geographic atrophy (GA) and Late AMD -neovascular (NV). Results: The presence of anti-retinal AAb was detected in 58% patients with Intermediate and Late AMD, and 54% of those with no AMD. AAbs bound to fifteen different retinal antigens. Most individuals had 1 specific AAbs (67%), with the remainder having 2 to 4 different AAbs. Over 40% of patients with Intermediate AMD, and 46% of those with GA had anti-enolase AAbs, compared with 29% of individuals with NV and 29% with no AMD. Different AAbs signatures related to NV as compared to GA and/or Intermediate AMD were distinguished. Anti-40-kDa (10%) and 42-kDa (16%) autoantibodies were associated with Intermediate AMD, while anti-30-kDa AAbs (23%) were primarily present in GA. Anti-32-kDa (12%), 35-kDa (21%), and 60-kDa (8%) AAbs were more frequent in NV AMD. Conclusions: A unique AAb pattern for each of the disease subgroups was present when AMD progressed from the intermediate to the late forms of severity. Differences in the frequency of specific AAbs between AMD subgroups suggested that they may participate in pathogenicity of AMD. Further studies are necessary to confirm these observations in the larger cohort and individual AMD patients over time. C1 [Adamus, Grazyna; Klein, Michael L.] Oregon Hlth & Sci Univ, Casey Eye Inst, Ocular Immunol Lab, Portland, OR 97239 USA. [Chew, Emily Y.; Ferris, Frederick L.] NEI, NIH, Bethesda, MD 20892 USA. RP Adamus, G (reprint author), Oregon Hlth & Sci Univ, Casey Eye Inst, Ocular Immunol Lab, L467AD,3181 SW Sam Jackson Pk Rd, Portland, OR 97239 USA. EM adamusg@ohsu.edu FU National Eye Institute [EY13053, EY021532]; Macular Degeneration Center Research Fund [P30EY010572]; Foundation to Prevent Blindness FX This work was supported in part by the National Eye Institute grants EY13053 (GA) and EY021532 (MK), the Macular Degeneration Center Research Fund (MK), core grant P30EY010572 and unrestricted grant to Casey Eye Institute from the Foundation to Prevent Blindness. NR 60 TC 4 Z9 4 U1 1 U2 2 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1471-2415 J9 BMC OPHTHALMOL JI BMC Ophthalmol. PD DEC 8 PY 2014 VL 14 AR 154 DI 10.1186/1471-2415-14-154 PG 9 WC Ophthalmology SC Ophthalmology GA AZ4BF UT WOS:000348166600001 PM 25488058 ER PT J AU Sourbier, C Ricketts, CJ Matsumoto, S Crooks, DR Liao, PJ Mannes, PZ Yang, Y Wei, MH Srivastava, G Ghosh, S Chen, V Vocke, CD Merino, M Srinivasan, R Krishna, MC Mitchell, JB Pendergast, AM Rouault, TA Neckers, L Linehan, WM AF Sourbier, Carole Ricketts, Christopher J. Matsumoto, Shingo Crooks, Daniel R. Liao, Pei-Jyun Mannes, Philip Z. Yang, Youfeng Wei, Ming-Hui Srivastava, Gaurav Ghosh, Sanchari Chen, Viola Vocke, Cathy D. Merino, Maria Srinivasan, Ramaprasad Krishna, Murali C. Mitchell, James B. Pendergast, Ann Marie Rouault, Tracey A. Neckers, Len Linehan, W. Marston TI Targeting ABL1-Mediated Oxidative Stress Adaptation in Fumarate Hydratase-Deficient Cancer SO CANCER CELL LA English DT Article ID RENAL-CELL CARCINOMA; KINASE INHIBITOR SELECTIVITY; HEREDITARY LEIOMYOMATOSIS; BCR-ABL; IN-VITRO; C-ABL; ACTIVATION; NRF2; PATHWAY; METABOLISM AB Patients with germline fumarate hydratase (FH) mutation are predisposed to develop aggressive kidney cancer with few treatment options and poor therapeutic outcomes. Activity of the proto-oncogene ABL1 is upregulated in FH-deficient kidney tumors and drives a metabolic and survival signaling network necessary to cope with impaired mitochondrial function and abnormal accumulation of intracellular fumarate. Excess fumarate indirectly stimulates ABL1 activity, while restoration of wild-type FH abrogates both ABL1 activation and the cytotoxicity caused by ABL1 inhibition or knockdown. ABL1 upregulates aerobic glycolysis via the mTOR/HIF1 alpha pathway and neutralizes fumarate-induced proteotoxic stress by promoting nuclear localization of the antioxidant response transcription factor NRF2. Our findings identify ABL1 as a pharmacologically tractable therapeutic target in glycolytically dependent, oxidatively stressed tumors. C1 [Sourbier, Carole; Ricketts, Christopher J.; Crooks, Daniel R.; Liao, Pei-Jyun; Mannes, Philip Z.; Yang, Youfeng; Wei, Ming-Hui; Srivastava, Gaurav; Ghosh, Sanchari; Chen, Viola; Vocke, Cathy D.; Srinivasan, Ramaprasad; Neckers, Len; Linehan, W. Marston] NCI, Urol Oncol Branch, Ctr Canc Res, Bethesda, MD 20892 USA. [Matsumoto, Shingo; Krishna, Murali C.; Mitchell, James B.] NCI, Radiat Biol Branch, Ctr Canc Res, Bethesda, MD 20892 USA. [Rouault, Tracey A.] Eunice Kennedy Shriver Natl Inst Child Hlth & Dev, Program Mol Med, Bethesda, MD 20892 USA. [Merino, Maria] NCI, Pathol Lab, Bethesda, MD 20892 USA. [Pendergast, Ann Marie] Duke Univ, Sch Med, Dept Pharmacol & Canc Biol, Durham, NC 27710 USA. RP Linehan, WM (reprint author), NCI, Urol Oncol Branch, Ctr Canc Res, Bethesda, MD 20892 USA. EM wml@nih.gov FU National Cancer Institute; Center for Cancer Research FX This research was supported by the Intramural Research Program of the National Cancer Institute, Center for Cancer Research. V.C. was supported by Howard Hughes Medical Institute. We acknowledge the outstanding editorial and graphics support by Georgia Shaw. We thank Dr. Carlos Torres-Cabala (Laboratory of Pathology, National Cancer Institute) for his help with immunohistochemistry and Mrs. Catherine Wells for technical assistance with the animal studies. NR 44 TC 16 Z9 16 U1 1 U2 16 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 1535-6108 EI 1878-3686 J9 CANCER CELL JI Cancer Cell PD DEC 8 PY 2014 VL 26 IS 6 BP 840 EP 850 DI 10.1016/j.ccell.2014.10.005 PG 11 WC Oncology; Cell Biology SC Oncology; Cell Biology GA AW2JN UT WOS:000346114000013 PM 25490448 ER PT J AU Tripathi, BK Qian, XL Mertins, P Wang, DR Papageorge, AG Carr, SA Lowy, DR AF Tripathi, Brajendra K. Qian, Xiaolan Mertins, Philipp Wang, Dunrui Papageorge, Alex G. Carr, Steven A. Lowy, Douglas R. TI CDK5 is a major regulator of the tumor suppressor DLC1 SO JOURNAL OF CELL BIOLOGY LA English DT Article ID GTPASE-ACTIVATING PROTEIN; CYCLIN-DEPENDENT KINASE-5; CANCER 1 DLC1; CELL-MIGRATION; RHO-GTPASES; SH2 DOMAIN; PHOSPHORYLATION; GENE; GROWTH; DIFFERENTIATION AB DLC1 is a tumor suppressor protein whose full activity depends on its presence at focal adhesions, its Rho-GTPase activating protein (RhoGAP) function, and its ability to bind several ligands, including tensin and talin. However, the mechanisms that regulate and coordinate these activities remain poorly understood. Here we identify CDK5, a predominantly cytoplasmic serine/threonine kinase, as an important regulator of DLC1 functions. The CDK5 kinase phosphorylates four serines in DLC1 located N-terminal to the Rho-GAP domain. When not phosphorylated, this N-terminal region functions as an autoinhibitory domain that places DLC1 in a closed, inactive conformation by efficiently binding to the Rho-GAP domain. CDK5 phosphorylation reduces this binding and orchestrates the coordinate activation DLC1, including its localization to focal adhesions, its RhoGAP activity, and its ability to bind tensin and talin. In cancer, these anti-oncogenic effects of CDK5 can provide selective pressure for the down-regulation of DLC1, which occurs frequently in tumors, and can contribute to the pro-oncogenic activity of CDK5 in lung adenocarcinoma. C1 [Tripathi, Brajendra K.; Qian, Xiaolan; Wang, Dunrui; Papageorge, Alex G.; Lowy, Douglas R.] NCI, Cellular Oncol Lab, NIH, Bethesda, MD 20892 USA. [Mertins, Philipp; Carr, Steven A.] Broad Inst MIT & Harvard, Cambridge, MA 02142 USA. RP Lowy, DR (reprint author), NCI, Cellular Oncol Lab, NIH, Bethesda, MD 20892 USA. EM tripathib@mail.nih.gov; lowyd@mail.nih.gov FU Intramural Research Program, National Institutes of Health, National Cancer Institute; Center for Cancer Research FX This research is supported by the Intramural Research Program, National Institutes of Health, National Cancer Institute, and Center for Cancer Research. NR 56 TC 12 Z9 12 U1 0 U2 6 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 950 THIRD AVE, 2ND FLR, NEW YORK, NY 10022 USA SN 0021-9525 EI 1540-8140 J9 J CELL BIOL JI J. Cell Biol. PD DEC 8 PY 2014 VL 207 IS 5 BP 627 EP 642 DI 10.1083/jcb.201405105 PG 16 WC Cell Biology SC Cell Biology GA AW3EA UT WOS:000346167300007 PM 25452387 ER PT J AU Wang, YS Thomas, A Lau, C Rajan, A Zhu, YL Killian, JK Petrini, I Pham, T Morrow, B Zhong, XG Meltzer, PS Giaccone, G AF Wang, Yisong Thomas, Anish Lau, Christopher Rajan, Arun Zhu, Yuelin Killian, J. Keith Petrini, Iacopo Pham, Trung Morrow, Betsy Zhong, Xiaogang Meltzer, Paul S. Giaccone, Giuseppe TI Mutations of epigenetic regulatory genes are common in thymic carcinomas SO SCIENTIFIC REPORTS LA English DT Article ID EPITHELIAL TUMORS; SOMATIC MUTATIONS; DNMT3A MUTATIONS; CANCER GENOMES; DNA; LEUKEMIA; MALIGNANCIES; THERAPIES; RECURRENT; DISEASES AB Genetic alterations and etiology of thymic epithelial tumors (TETs) are largely unknown, hampering the development of effective targeted therapies for patients with TETs. Here TETs of advanced-stage patients enrolled in a clinical trial of molecularly-guided targeted therapies were employed for targeted sequencing of 197 cancer-associated genes. Comparative sequence analysis of 78 TET/blood paired samples obtained from 47 thymic carcinoma (TC) and 31 thymoma patients revealed a total of 86 somatic non-synonymous sequence variations across 39 different genes in 33 (42%) TETs. TCs (62%; 29/47) showed higher incidence of somatic non-synonymous mutations than thymomas (13%; 4/31; p < 0.0001). TP53 was the most frequently mutated gene in TETs (n = 13; 17%), especially in TCs (26%), and was associated with a poorer overall survival (p, 0.0001). Genes in histone modification [BAP1 (n = 6; 13%), SETD2 (n = 5; 11%), ASXL1 (n = 2; 4%)], chromatin remodeling [SMARCA4 (n = 2; 4%)], and DNA methylation [DNMT3A (n = 3; 7%), TET2 (n = 2; 4%), WT1 (n = 2; 4%)] pathways were recurrently mutated in TCs, but not in thymomas. Our results suggest a potential disruption of epigenetic homeostasis in TCs, and a substantial difference in genetic makeup between TCs and thymomas. Further investigation is warranted into the roles of epigenetic dysregulation in TC development and its potential for targeted therapy. C1 [Wang, Yisong; Thomas, Anish; Lau, Christopher; Rajan, Arun; Zhu, Yuelin; Killian, J. Keith; Petrini, Iacopo; Pham, Trung; Morrow, Betsy; Meltzer, Paul S.; Giaccone, Giuseppe] NCI, Ctr Canc Res, Bethesda, MD 20892 USA. [Zhong, Xiaogang; Giaccone, Giuseppe] Georgetown Univ, Lombardi Comprehens Canc Ctr, Washington, DC 20007 USA. RP Giaccone, G (reprint author), NCI, Ctr Canc Res, Bethesda, MD 20892 USA. EM gg496@georgetown.edu RI Petrini, Iacopo/K-7316-2016; Giaccone, Giuseppe/E-8297-2017; OI Petrini, Iacopo/0000-0002-7752-6866; Giaccone, Giuseppe/0000-0002-5023-7562; Thomas, Anish/0000-0003-3293-3115 FU NIH/NCI intramural research program; Lombardi Cancer Center, Georgetown University FX The study was supported by NIH/NCI intramural research program and by Lombardi Cancer Center, Georgetown University. NR 55 TC 12 Z9 12 U1 2 U2 8 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 2045-2322 J9 SCI REP-UK JI Sci Rep PD DEC 8 PY 2014 VL 4 AR 7336 DI 10.1038/srep07336 PG 11 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA AW4TJ UT WOS:000346273000001 PM 25482724 ER PT J AU Ghitza, UE AF Ghitza, Udi E. TI ASPIRE model for treating cannabis and other substance use disorders: a novel personalized-medicine framework SO FRONTIERS IN PSYCHIATRY LA English DT Editorial Material DE substance use disorder; drug abuse; substance abuse; addiction; dependence; addiction treatment; substance abuse treatment; drug abuse treatment C1 [Ghitza, Udi E.] NIDA, Ctr Clin Trials Network, NIH, Bethesda, MD 20892 USA. RP Ghitza, UE (reprint author), NIDA, Ctr Clin Trials Network, NIH, Bethesda, MD 20892 USA. EM ghitzau@nida.nih.gov NR 27 TC 4 Z9 4 U1 1 U2 1 PU FRONTIERS MEDIA SA PI LAUSANNE PA PO BOX 110, EPFL INNOVATION PARK, BUILDING I, LAUSANNE, 1015, SWITZERLAND SN 1664-0640 J9 FRONT PSYCHIATRY JI Front. Psychiatry PD DEC 8 PY 2014 VL 5 DI 10.3389/fpsyt.2014.00180 PG 4 WC Psychiatry SC Psychiatry GA V46XP UT WOS:000209917200001 PM 25538635 ER PT J AU Benjamini, D Basser, PJ AF Benjamini, Dan Basser, Peter J. TI Joint radius-length distribution as a measure of anisotropic pore eccentricity: An experimental and analytical framework SO JOURNAL OF CHEMICAL PHYSICS LA English DT Article ID FIELD-GRADIENT; SIZE DISTRIBUTION; SKELETAL-MUSCLE; NERVE-FIBERS; PULSED NMR; DIFFUSION; MR; POROSITY; BONE; PFG AB In this work, we present an experimental design and analytical framework to measure the non-parametric joint radius-length (R-L) distribution of an ensemble of parallel, finite cylindrical pores, and more generally, the eccentricity distribution of anisotropic pores. Employing a novel 3D double pulsed-field gradient acquisition scheme, we first obtain both the marginal radius and length distributions of a population of cylindrical pores and then use these to constrain and stabilize the estimate of the joint radius-length distribution. Using the marginal distributions as constraints allows the joint R-L distribution to be reconstructed from an underdetermined system (i.e., more variables than equations), which requires a relatively small and feasible number of MR acquisitions. Three simulated representative joint R-L distribution phantoms corrupted by different noise levels were reconstructed to demonstrate the process, using this new framework. As expected, the broader the peaks in the joint distribution, the less stable and more sensitive to noise the estimation of the marginal distributions. Nevertheless, the reconstruction of the joint distribution is remarkably robust to increases in noise level; we attribute this characteristic to the use of the marginal distributions as constraints. Axons are known to exhibit local compartment eccentricity variations upon injury; the extent of the variations depends on the severity of the injury. Nonparametric estimation of the eccentricity distribution of injured axonal tissue is of particular interest since generally one cannot assume a parametric distribution a priori. Reconstructing the eccentricity distribution may provide vital information about changes resulting from injury or that occurred during development. C1 [Benjamini, Dan; Basser, Peter J.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Sect Tissue Biophys & Biomimet, PPITS, NIH, Bethesda, MD 20892 USA. [Benjamini, Dan] Tel Aviv Univ, Dept Biomed Engn, Iby & Aladar Fleischman Fac Engn, IL-69978 Tel Aviv, Israel. RP Basser, PJ (reprint author), Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Sect Tissue Biophys & Biomimet, PPITS, NIH, Bethesda, MD 20892 USA. EM basserp@helix.nih.gov FU Intramural Research Program of the Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) FX This work was supported by funds provided by the Intramural Research Program of the Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD). The authors would like to thank Dr. Michal Komlosh and Dr. Alexandru Avram for the helpful discussions. D.B. would like to thank Dr. Uri Nevo for his advice and guidance. We thank L. Salak for editing the paper. NR 47 TC 5 Z9 5 U1 0 U2 9 PU AMER INST PHYSICS PI MELVILLE PA CIRCULATION & FULFILLMENT DIV, 2 HUNTINGTON QUADRANGLE, STE 1 N O 1, MELVILLE, NY 11747-4501 USA SN 0021-9606 EI 1089-7690 J9 J CHEM PHYS JI J. Chem. Phys. PD DEC 7 PY 2014 VL 141 IS 21 AR 214202 DI 10.1063/1.4901134 PG 12 WC Chemistry, Physical; Physics, Atomic, Molecular & Chemical SC Chemistry; Physics GA AW0XJ UT WOS:000346014200016 PM 25481136 ER PT J AU Zitserman, VY Berezhkovskii, AM Antipov, AE Makhnovskii, YA AF Zitserman, Vladimir Yu Berezhkovskii, Alexander M. Antipov, Anatoly E. Makhnovskii, Yurii A. TI Biased diffusion in tubes of alternating diameter: Analytical treatment in the case of strong bias SO JOURNAL OF CHEMICAL PHYSICS LA English DT Article ID BROWNIAN MOTORS; TRANSPORT AB This paper is devoted to the effective transport coefficients of a particle in a tube of alternating diameter. Analytical expressions are derived for the effective mobility and diffusivity under strong bias conditions, i.e., in the limiting case where the external biasing force tends to infinity. The expressions give the transport coefficients as functions of the geometric parameters of the tube and the external force. They show that the effective diffusivity is a linear function of the square of the external force, whereas the effective mobility is independent of the force. The problem of finding effective transport coefficients in a tube of alternating diameter is too complex to be analyzed by conventional methods. Therefore, the expressions are derived in the framework of an intuition-based approach and validated by Brownian dynamics simulations. The obtained results extend a short list of available analytical expressions for the effective transport coefficients. (C) 2014 AIP Publishing LLC. C1 [Zitserman, Vladimir Yu] Russian Acad Sci, Joint Inst High Temp, Moscow 125412, Russia. [Berezhkovskii, Alexander M.] NIH, Math & Stat Comp Lab, Div Computat Biosci, Ctr Informat Technol, Bethesda, MD 20819 USA. [Antipov, Anatoly E.] Moscow MV Lomonosov State Univ, Fac Fundamental Phys & Chem Engn, Moscow 19991, Russia. [Makhnovskii, Yurii A.] Russian Acad Sci, Topchiev Inst Petrochem Synth, Moscow 19991, Russia. RP Zitserman, VY (reprint author), Russian Acad Sci, Joint Inst High Temp, Izhorskaya 13,Bldg 2, Moscow 125412, Russia. FU Russian Foundation for Basic Research [14-03-00343]; Presidium of Russian Academy of Sciences [1]; Ministry of Education and Science of the Russian Federation [11.G34.31.0055]; Intramural Research Program of the NIH, Center for Information Technology FX V.Yu.Z., A.E.A., and Yu.A.M. thank the Russian Foundation for Basic Research for partial support (Grant No. 14-03-00343). V.Yu.Z. is grateful for partial support to the Program of Basic Research No. 1 of Presidium of Russian Academy of Sciences "Fundamental Problems of Mathematical Modeling" (supervisor academician V. B. Betelin). A.E.A. and Yu.A.M. thank Ministry of Education and Science of the Russian Federation for partial support (Grant No. 11.G34.31.0055). This study was supported by the Intramural Research Program of the NIH, Center for Information Technology. NR 19 TC 1 Z9 1 U1 2 U2 9 PU AMER INST PHYSICS PI MELVILLE PA CIRCULATION & FULFILLMENT DIV, 2 HUNTINGTON QUADRANGLE, STE 1 N O 1, MELVILLE, NY 11747-4501 USA SN 0021-9606 EI 1089-7690 J9 J CHEM PHYS JI J. Chem. Phys. PD DEC 7 PY 2014 VL 141 IS 21 AR 214103 DI 10.1063/1.4902552 PG 8 WC Chemistry, Physical; Physics, Atomic, Molecular & Chemical SC Chemistry; Physics GA AW0XJ UT WOS:000346014200005 PM 25481125 ER PT J AU Bhar, S Mirabello, L Chatterjee, N Williams, C Alter, BP Giri, N Person, R Landsverk, M Eng, C Savage, SA Bertuch, A AF Bhar, Saleh Mirabello, Lisa Chatterjee, Nimrat Williams, Christopher Alter, Blanche P. Giri, Neelam Person, Richard Landsverk, Megan Eng, Christine Savage, Sharon A. Bertuch, Alison TI De Novo RPS20 Mutations in Diamond Blackfan Anemia SO BLOOD LA English DT Meeting Abstract C1 [Bhar, Saleh; Chatterjee, Nimrat; Williams, Christopher; Person, Richard; Landsverk, Megan; Eng, Christine; Bertuch, Alison] Baylor Coll Med, Houston, TX 77030 USA. [Bhar, Saleh] Texas Childrens Hosp, Houston, TX 77030 USA. [Mirabello, Lisa] NCI, Bethesda, MD 20892 USA. [Alter, Blanche P.] NCI, NIH, Rockville, MD USA. [Giri, Neelam; Savage, Sharon A.] NCI, Rockville, MD USA. RI Savage, Sharon/B-9747-2015 OI Savage, Sharon/0000-0001-6006-0740 NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 2021 L ST NW, SUITE 900, WASHINGTON, DC 20036 USA SN 0006-4971 EI 1528-0020 J9 BLOOD JI Blood PD DEC 6 PY 2014 VL 124 IS 21 PG 3 WC Hematology SC Hematology GA CA9KQ UT WOS:000349242704092 ER PT J AU Ciurea, SO Zhang, MJ Bacigalupo, A Bashey, A Appelbaum, FR Antin, JH Chen, JF Devine, SM Fowler, DH Nakamura, R Perales, MA Pingali, SR Porter, DL Ringden, O Rocha, V Vij, R Weisdorf, DJ Champlin, RE Fuchs, EJ Eapen, M AF Ciurea, Stefan O. Zhang, Mei-Jie Bacigalupo, Andrea Bashey, Asad Appelbaum, Frederick R. Antin, Joseph H. Chen, Junfang Devine, Steven M. Fowler, Daniel H. Nakamura, Ryotaro Perales, Miguel-Angel Pingali, Sai Ravi Porter, David L. Ringden, Olle Rocha, Vanderson Vij, Ravi Weisdorf, Daniel J. Champlin, Richard E. Fuchs, Ephraim J. Eapen, Mary TI Survival after T-Cell Replete Haplo-Identical Related Donor Transplant Using Post-Transplant Cyclophosphamide Compared with Matched Unrelated Donor Transplant for Acute Myeloid Leukemia SO BLOOD LA English DT Meeting Abstract C1 [Ciurea, Stefan O.; Pingali, Sai Ravi; Champlin, Richard E.] Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA. [Zhang, Mei-Jie; Chen, Junfang; Eapen, Mary] Med Coll Wisconsin, Milwaukee, WI 53226 USA. [Bacigalupo, Andrea] IRCCS AOU San Martino IST, Genoa, Italy. [Bashey, Asad] Northside Hosp, Blood & Marrow Transplant Program, Atlanta, GA USA. [Appelbaum, Frederick R.] Fred Hutchinson Canc Res Ctr, Seattle, WA 98104 USA. [Antin, Joseph H.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Devine, Steven M.] Ohio State Univ, Ctr Comprehens Canc, Columbus, OH 43210 USA. [Fowler, Daniel H.] NCI, Bethesda, MD 20892 USA. [Nakamura, Ryotaro] City Hope Natl Med Ctr, Duarte, CA USA. [Perales, Miguel-Angel] Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. [Porter, David L.] Univ Penn, Abramson Canc Ctr, Philadelphia, PA 19104 USA. [Ringden, Olle] Karolinska Univ Hosp Huddinge, Stockholm, Sweden. [Rocha, Vanderson] Churchill Hosp, Oxford OX3 7LJ, England. [Vij, Ravi] Washington Univ, Sch Med, St Louis, MO USA. [Weisdorf, Daniel J.] Univ Minnesota, Minneapolis, MN USA. [Fuchs, Ephraim J.] Johns Hopkins Univ, Baltimore, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 2021 L ST NW, SUITE 900, WASHINGTON, DC 20036 USA SN 0006-4971 EI 1528-0020 J9 BLOOD JI Blood PD DEC 6 PY 2014 VL 124 IS 21 PG 4 WC Hematology SC Hematology GA CA9KQ UT WOS:000349242708145 ER PT J AU Cuellar-Rodriguez, J Hickstein, DD Grossman, JK Parta, M Gea-Banacloche, J Zerbe, CS Freeman, AF Holland, SM Calvo, KR AF Cuellar-Rodriguez, Jennifer Hickstein, Dennis D. Grossman, Jennifer K. Parta, Mark Gea-Banacloche, Juan Zerbe, Christa S. Freeman, Alexandra F. Holland, Steven M. Calvo, Katherine R. TI Nonmyeloablative Versus Myeloablative Allogeneic Hematopoietic Stem Cell Transplant for GATA2 Deficiency SO BLOOD LA English DT Meeting Abstract C1 [Cuellar-Rodriguez, Jennifer; Zerbe, Christa S.; Freeman, Alexandra F.] NIAID, Bethesda, MD 20892 USA. [Hickstein, Dennis D.; Parta, Mark; Gea-Banacloche, Juan; Holland, Steven M.; Calvo, Katherine R.] NIH, Bethesda, MD 20892 USA. [Grossman, Jennifer K.] Univ Calgary, Calgary, AB, Canada. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 2021 L ST NW, SUITE 900, WASHINGTON, DC 20036 USA SN 0006-4971 EI 1528-0020 J9 BLOOD JI Blood PD DEC 6 PY 2014 VL 124 IS 21 PG 3 WC Hematology SC Hematology GA CA9KQ UT WOS:000349242701058 ER PT J AU Dale, DC Bolyard, AA Zeidler, C Marrero, TM Boxer, LA Newburger, PE Alter, BP Morrow, PK Bonilla, MA Dror, Y Firkin, F Kinsey, S Levine, JE Link, DC Reeves, L Rosenberg, PS Shimamura, A Welte, K AF Dale, David C. Bolyard, Audrey Anna Zeidler, Cornelia Marrero, Tracy M. Boxer, Laurence A. Newburger, Peter E. Alter, Blanche P. Morrow, P. K. Bonilla, Mary Ann Dror, Yigal Firkin, Frank Kinsey, Sally Levine, John E. Link, Daniel C. Reeves, Lee Rosenberg, Philip S. Shimamura, Akiko Welte, Karl TI Understanding Neutropenia: The 20 Year Experience of the Severe Chronic Neutropenia International Registry (SCNIR) SO BLOOD LA English DT Meeting Abstract C1 [Dale, David C.; Bolyard, Audrey Anna] Univ Washington, Seattle, WA 98195 USA. [Zeidler, Cornelia; Welte, Karl] Hannover Med Sch, Hannover, Germany. [Marrero, Tracy M.] Univ Washington, Severe Chron Neutropenia Int Registry, Seattle, WA 98195 USA. [Boxer, Laurence A.] Univ Michigan Hlth Syst, Ann Arbor, MI USA. [Newburger, Peter E.] Univ Massachusetts, Sch Med, Worcester, MA USA. [Alter, Blanche P.; Rosenberg, Philip S.] NCI, NIH, Rockville, MD USA. [Morrow, P. K.] Global Dev, Thousand Oaks, CA USA. [Bonilla, Mary Ann] St Josephs Childrens Hosp, Paterson, NJ USA. [Dror, Yigal] Hosp Sick Children, Toronto, ON M5G 1X8, Canada. [Dror, Yigal] Genet & Genome Biol Program, Toronto, ON, Canada. [Dror, Yigal] Univ Toronto, Inst Med Sci, Toronto, ON, Canada. [Firkin, Frank] St Vincents Hosp Melbourne, Fitzroy, Vic, Australia. [Kinsey, Sally] Leeds Teaching Hosp, Leeds, W Yorkshire, England. [Levine, John E.] Univ Michigan, Med Ctr, Ann Arbor, MI USA. [Link, Daniel C.] Washington Univ, Sch Med, St Louis, MO USA. [Reeves, Lee] Natl Neutropenia Network, Brighton, MI USA. [Shimamura, Akiko] Fred Hutchinson Canc Res Ctr, Seattle, WA 98104 USA. NR 0 TC 0 Z9 0 U1 1 U2 2 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 2021 L ST NW, SUITE 900, WASHINGTON, DC 20036 USA SN 0006-4971 EI 1528-0020 J9 BLOOD JI Blood PD DEC 6 PY 2014 VL 124 IS 21 PG 3 WC Hematology SC Hematology GA CA9KQ UT WOS:000349242702106 ER PT J AU de Vasconcellos, JF Byrnes, C Lee, YT Kaushal, M Allwardt, JM Rabel, A Miller, JL AF de Vasconcellos, Jaira F. Byrnes, Colleen Lee, Y. Terry Kaushal, Megha Allwardt, Joshua M. Rabel, Antoinette Miller, Jeffery L. TI Targeted Reduction of Let-7a miRNA Increases Fetal Hemoglobin in Human Adult Erythroblasts SO BLOOD LA English DT Meeting Abstract C1 [de Vasconcellos, Jaira F.; Byrnes, Colleen; Lee, Y. Terry; Kaushal, Megha; Allwardt, Joshua M.; Rabel, Antoinette; Miller, Jeffery L.] NIDDK, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 2021 L ST NW, SUITE 900, WASHINGTON, DC 20036 USA SN 0006-4971 EI 1528-0020 J9 BLOOD JI Blood PD DEC 6 PY 2014 VL 124 IS 21 PG 3 WC Hematology SC Hematology GA CA9KQ UT WOS:000349242704209 ER PT J AU Di Maggio, R Hsieh, M Fitzhugh, C Zhao, XC Calvaruso, G Rigano, P Renda, D Siragusa, S Tisdale, JF Maggio, A AF Di Maggio, Rosario Hsieh, Matthew Fitzhugh, Courtney Zhao, Xiongce Calvaruso, Giusi Rigano, Paolo Renda, Disma Siragusa, Sergio Tisdale, John F. Maggio, Aurelio TI Chronic Administration of Hydroxyurea (HU) and Outcomes in Patients with Sickle Cell Disease (SCD) at a Single Referral Institution SO BLOOD LA English DT Meeting Abstract C1 [Di Maggio, Rosario; Maggio, Aurelio] AOR Villa Sofia V Cervello, Palermo, Italy. [Hsieh, Matthew; Tisdale, John F.] NHLBI, NIDDK, NIH, Bethesda, MD 20892 USA. [Fitzhugh, Courtney] NHLBI, NIH, Bethesda, MD 20892 USA. [Zhao, Xiongce] NIDDK, NIH, Bethesda, MD 20892 USA. [Calvaruso, Giusi] AO Villa Sofia V Cervello, Palermo, Italy. [Rigano, Paolo; Renda, Disma] Osped Riuniti Villa Sofia Cervello, Palermo, Italy. [Siragusa, Sergio] Policlin Univ Palermo, Palermo, Italy. NR 0 TC 0 Z9 0 U1 0 U2 2 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 2021 L ST NW, SUITE 900, WASHINGTON, DC 20036 USA SN 0006-4971 EI 1528-0020 J9 BLOOD JI Blood PD DEC 6 PY 2014 VL 124 IS 21 PG 3 WC Hematology SC Hematology GA CA9KQ UT WOS:000349242706043 ER PT J AU Dolai, S Sia, KCS Robbins, AK Zhong, L Heatley, S Vincent, T Hochgrafe, F Kurmasheva, RT White, DL Houghton, PJ Smith, MA Teachey, DT Daly, RJ Raftery, MJ Lock, RB AF Dolai, Sibasish Sia, Keith C. S. Robbins, Alissa K. Zhong, Ling Heatley, Sue Vincent, Tiffaney Hochgraefe, Falko Kurmasheva, Raushan T. White, Deborah L. Houghton, Peter J. Smith, Malcolm A. Teachey, David T. Daly, Roger J. Raftery, Mark J. Lock, Richard B. TI Targeted Cancer Therapy in High-Risk Pediatric Leukemia Using Global Phosphotyrosine Profiling SO BLOOD LA English DT Meeting Abstract C1 [Dolai, Sibasish; Sia, Keith C. S.; Robbins, Alissa K.; Zhong, Ling; Raftery, Mark J.; Lock, Richard B.] Univ New S Wales, Sydney, NSW, Australia. [Heatley, Sue; White, Deborah L.] SAHMRI, Adelaide, SA, Australia. [Vincent, Tiffaney; Teachey, David T.] Childrens Hosp Philadelphia, Philadelphia, PA 19104 USA. [Hochgraefe, Falko] Ernst Moritz Arndt Univ Greifswald, Greifswald, Germany. [Kurmasheva, Raushan T.; Houghton, Peter J.] Nationwide Childrens Hosp, Columbus, OH USA. [Smith, Malcolm A.] NCI, Bethesda, MD 20892 USA. [Daly, Roger J.] Monash Univ, Clayton, Vic 3800, Australia. NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 2021 L ST NW, SUITE 900, WASHINGTON, DC 20036 USA SN 0006-4971 EI 1528-0020 J9 BLOOD JI Blood PD DEC 6 PY 2014 VL 124 IS 21 PG 3 WC Hematology SC Hematology GA CA9KQ UT WOS:000349242705041 ER PT J AU Du, E Mendelsohn, L Nichols, JS Dao, M Kato, GJ AF Du, E. Mendelsohn, Laurel Nichols, James S. Dao, Ming Kato, Gregory J. TI Quantification of Anti-Sickling Effect of Aes-103 in Sickle Cell Disease Using an in Vitro Microfluidic Assay SO BLOOD LA English DT Meeting Abstract C1 [Du, E.; Dao, Ming] MIT, Boston, MA USA. [Mendelsohn, Laurel; Nichols, James S.] NHLBI, Bethesda, MD 20892 USA. [Kato, Gregory J.] Univ Pittsburgh, Pittsburgh, PA USA. RI Dao, Ming/B-1602-2008; Kato, Gregory/I-7615-2014 OI Kato, Gregory/0000-0003-4465-3217 NR 0 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 0006-4971 EI 1528-0020 J9 BLOOD JI Blood PD DEC 6 PY 2014 VL 124 IS 21 PG 3 WC Hematology SC Hematology GA CA9KQ UT WOS:000349242706039 ER PT J AU Dunleavy, K Fanale, M LaCasce, A Noy, A Caimi, P Parekh, S Hayslip, JW Jagadeesh, D Lord, RS Lechowicz, MJ Gaur, R Lucas, A Staudt, LM Steinberg, SM Kahl, B Friedberg, JW Little, RF Bartlett, NL Wilson, WH AF Dunleavy, Kieron Fanale, Michelle LaCasce, Ann Noy, Ariela Caimi, Paolo Parekh, Samir Hayslip, John W. Jagadeesh, Deepa Lord, Raymond S. Lechowicz, Mary J. Gaur, Rakesh Lucas, Andrea Staudt, Louis M. Steinberg, Seth M. Kahl, Brad Friedberg, Jonathan W. Little, Richard F. Bartlett, Nancy L. Wilson, Wyndham H. TI Preliminary Report of a Multicenter Prospective Phase II Study of DA-EPOCH-R in MYC-Rearranged Aggressive B-Cell Lymphoma SO BLOOD LA English DT Meeting Abstract C1 [Dunleavy, Kieron; Lucas, Andrea; Staudt, Louis M.; Steinberg, Seth M.; Little, Richard F.; Wilson, Wyndham H.] NCI, Bethesda, MD 20892 USA. [Fanale, Michelle] Univ Texas, Houston, TX USA. [LaCasce, Ann] Dana Farber Canc Inst, Boston, MA 02115 USA. [Noy, Ariela] Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. [Caimi, Paolo] Case Western Reserve Univ, Cleveland, OH 44106 USA. [Parekh, Samir] Icahn Sch Med Mt Sinai, New York, NY 10029 USA. [Hayslip, John W.] Univ Kentucky, Lexington, KY USA. [Jagadeesh, Deepa] Cleveland Clin, Cleveland, OH 44106 USA. [Lord, Raymond S.] West Michigan Canc Ctr, Kalamazoo, MI USA. [Lechowicz, Mary J.] Emory Univ, Sch Med, Atlanta, GA USA. [Gaur, Rakesh] Kansas City CCOP, Kansas City, KS USA. [Kahl, Brad] UW Carbone Canc Ctr, Madison, WI USA. [Friedberg, Jonathan W.] Univ Rochester, Rochester, NY USA. [Bartlett, Nancy L.] Washington Univ, Sch Med, St Louis, MO USA. NR 0 TC 0 Z9 0 U1 3 U2 10 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 2021 L ST NW, SUITE 900, WASHINGTON, DC 20036 USA SN 0006-4971 EI 1528-0020 J9 BLOOD JI Blood PD DEC 6 PY 2014 VL 124 IS 21 PG 3 WC Hematology SC Hematology GA CA9KQ UT WOS:000349242707201 ER PT J AU Gerecitano, JF Hamlin, P Horwitz, SM Matasar, MJ Moskowitz, AJ Moskowitz, CH Noy, A Portlock, CS Palomba, ML Straus, DJ Younes, A Zelenetz, AD Chen, A Little, RF Fallon, F Whang, JH AF Gerecitano, John F. Hamlin, Paul Horwitz, Steven M. Matasar, Matthew J. Moskowitz, Alison J. Moskowitz, Craig H. Noy, Ariela Portlock, Carol S. Palomba, Maria Lia Straus, David J. Younes, Anas Zelenetz, Andrew D. Chen, Alice Little, Richard F. Fallon, France Whang, Juho TI Safety and Early Efficacy Analysis of a Novel Combination of the PARP Inhibitor Veliparib (ABT-888) Plus Bendamustine and Rituximab in Patients with Lymphoma SO BLOOD LA English DT Meeting Abstract C1 [Horwitz, Steven M.; Matasar, Matthew J.; Moskowitz, Alison J.; Moskowitz, Craig H.; Noy, Ariela; Portlock, Carol S.; Palomba, Maria Lia; Straus, David J.; Zelenetz, Andrew D.; Fallon, France; Whang, Juho] Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. [Younes, Anas] Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA. [Chen, Alice] NCI, Rockville, MD USA. [Little, Richard F.] NCI, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 2021 L ST NW, SUITE 900, WASHINGTON, DC 20036 USA SN 0006-4971 EI 1528-0020 J9 BLOOD JI Blood PD DEC 6 PY 2014 VL 124 IS 21 PG 3 WC Hematology SC Hematology GA CA9KQ UT WOS:000349242704065 ER PT J AU Giri, N Alter, BP Savage, SA Stratton, P AF Giri, Neelam Alter, Blanche P. Savage, Sharon A. Stratton, Pamela TI Fertility and Pregnancy Outcomes in Females with Dyskeratosis Congenita SO BLOOD LA English DT Meeting Abstract C1 [Giri, Neelam; Alter, Blanche P.; Savage, Sharon A.] NCI, Rockville, MD USA. [Stratton, Pamela] Program Reprod & Adult Endocrinol, Bethesda, MD USA. RI Savage, Sharon/B-9747-2015 OI Savage, Sharon/0000-0001-6006-0740 NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 2021 L ST NW, SUITE 900, WASHINGTON, DC 20036 USA SN 0006-4971 EI 1528-0020 J9 BLOOD JI Blood PD DEC 6 PY 2014 VL 124 IS 21 PG 3 WC Hematology SC Hematology GA CA9KQ UT WOS:000349242703067 ER PT J AU Goswami, M McGowan, KS Lu, K Jain, NA Candia, J Hensel, NF Tang, JR Calvo, KR Battiwalla, M Barrett, AJ Hourigan, CS AF Goswami, Meghali McGowan, Katherine S. Lu, Kit Jain, Natasha A. Candia, Julian Hensel, Nancy F. Tang, Jingrong Calvo, Katherine R. Battiwalla, Minoo Barrett, Austin John Hourigan, Christopher S. TI A Novel Multi-Gene Array Allows Relapse Risk Stratification in Acute Myeloid Leukemia Patients Undergoing Stem Cell Transplantation SO BLOOD LA English DT Meeting Abstract C1 [Goswami, Meghali; McGowan, Katherine S.; Lu, Kit; Jain, Natasha A.; Hensel, Nancy F.; Tang, Jingrong; Battiwalla, Minoo; Barrett, Austin John; Hourigan, Christopher S.] NHLBI, Hematol Branch, NIH, Bethesda, MD 20892 USA. [Candia, Julian] Univ Maryland, Dept Phys, College Pk, MD 20742 USA. [Calvo, Katherine R.] NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 2021 L ST NW, SUITE 900, WASHINGTON, DC 20036 USA SN 0006-4971 EI 1528-0020 J9 BLOOD JI Blood PD DEC 6 PY 2014 VL 124 IS 21 PG 4 WC Hematology SC Hematology GA CA9KQ UT WOS:000349242704164 ER PT J AU Haetscher, N Feuermann, YD Wingert, S Rehage, M Weiser, C Thalheimer, FB Bohnenberger, H Schroeder, T Serve, H Oellerich, T Hennighausen, L Rieger, MA AF Haetscher, Nadine Feuermann, Yonatan D. Wingert, Susanne Rehage, Maike Weiser, Christian Thalheimer, Frederic B. Bohnenberger, Hanibal Schroeder, Timm Serve, Hubert Oellerich, Thomas Hennighausen, Lothar Rieger, Michael A. TI STAT5-Regulated miRNA193b Controls Hematopoietic Stem and Progenitor Cell Expansion By Fine Tuning Cytokine Signaling SO BLOOD LA English DT Meeting Abstract C1 [Haetscher, Nadine; Feuermann, Yonatan D.; Wingert, Susanne; Rehage, Maike; Thalheimer, Frederic B.; Serve, Hubert; Oellerich, Thomas; Rieger, Michael A.] Goethe Univ Hosp, Dept Hematol Oncol, Frankfurt, Germany. [Haetscher, Nadine; Feuermann, Yonatan D.; Wingert, Susanne; Rehage, Maike; Thalheimer, Frederic B.; Rieger, Michael A.] LOEWE Ctr Cell & Gene Therapy, Frankfurt, Germany. [Feuermann, Yonatan D.; Hennighausen, Lothar] NIDDK, Lab Genet & Physiol, NIH, Bethesda, MD 20892 USA. [Bohnenberger, Hanibal] Univ Med Ctr Gottingen, Inst Pathol, Gottingen, Germany. [Schroeder, Timm] Dept Biosyst Sci & Engn D BSSE, Zurich, Switzerland. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 2021 L ST NW, SUITE 900, WASHINGTON, DC 20036 USA SN 0006-4971 EI 1528-0020 J9 BLOOD JI Blood PD DEC 6 PY 2014 VL 124 IS 21 PG 3 WC Hematology SC Hematology GA CA9KQ UT WOS:000349242703080 ER PT J AU Ishii, K Birmann, BM Zhang, XH Giovannucci, E Bertrand, KA AF Ishii, Kazusa Birmann, Brenda M. Zhang, Xuehong Giovannucci, Edward Bertrand, Kimberly A. TI A Prospective Analysis of Blood Donation History and Incidence of Non-Hodgkin Lymphoma SO BLOOD LA English DT Meeting Abstract C1 [Ishii, Kazusa] NIH, Bethesda, MD 20892 USA. [Birmann, Brenda M.; Zhang, Xuehong; Giovannucci, Edward; Bertrand, Kimberly A.] Brigham & Womens Hosp, Boston, MA 02115 USA. [Birmann, Brenda M.; Zhang, Xuehong; Giovannucci, Edward; Bertrand, Kimberly A.] Harvard Univ, Sch Med, Boston, MA USA. [Giovannucci, Edward; Bertrand, Kimberly A.] Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 2021 L ST NW, SUITE 900, WASHINGTON, DC 20036 USA SN 0006-4971 EI 1528-0020 J9 BLOOD JI Blood PD DEC 6 PY 2014 VL 124 IS 21 PG 3 WC Hematology SC Hematology GA CA9KQ UT WOS:000349242700132 ER PT J AU Ito, S Barrett, J Savani, BN Jagasia, M Brissot, E Miner, S Hensel, NF Chinian, F Keyvanfar, K Battiwalla, M Savona, MR Mohan, S Carlsten, M Muranski, P Strickland, SA AF Ito, Sawa Barrett, John Savani, Bipin N. Jagasia, Madan Brissot, Eolia Miner, Samantha Hensel, Nancy F. Chinian, Fariba Keyvanfar, Keyvan Battiwalla, Minoo Savona, Michael R. Mohan, Sanjay Carlsten, Mattias Muranski, Pawel Strickland, Stephen A. TI A Suppressive Microenvironment in Acute Myeloid Leukemia Induces Global Alteration of T and NK Cell Profiles - Evidence for Immune-Editing Effect By Leukemia SO BLOOD LA English DT Meeting Abstract C1 [Ito, Sawa; Barrett, John; Brissot, Eolia; Miner, Samantha; Hensel, Nancy F.; Chinian, Fariba; Keyvanfar, Keyvan; Battiwalla, Minoo; Carlsten, Mattias; Muranski, Pawel] NHLBI, NIH, Bethesda, MD 20892 USA. [Savani, Bipin N.; Jagasia, Madan; Savona, Michael R.; Mohan, Sanjay; Strickland, Stephen A.] Vanderbilt Univ, Med Ctr, Nashville, TN USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 2021 L ST NW, SUITE 900, WASHINGTON, DC 20036 USA SN 0006-4971 EI 1528-0020 J9 BLOOD JI Blood PD DEC 6 PY 2014 VL 124 IS 21 PG 3 WC Hematology SC Hematology GA CA9KQ UT WOS:000349242706053 ER PT J AU Kekre, N Mak, K Binder, M Branvall, E Ishii, K Stopsack, K Cutler, CS AF Kekre, Natasha Mak, Kimberley Binder, Moritz Branvall, Elsa Ishii, Kazusa Stopsack, Konrad Cutler, Corey S. TI Meta-Analysis of HLA-Mismatched Compared to HLA-Matched Hematopoietic Stem Cell Transplantation SO BLOOD LA English DT Meeting Abstract C1 [Kekre, Natasha; Cutler, Corey S.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Mak, Kimberley] Harvard Radiat Oncol Program, Boston, MA USA. [Binder, Moritz; Stopsack, Konrad] Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA. [Branvall, Elsa] Karolinska Univ Hosp, Stockholm, Sweden. [Ishii, Kazusa] NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 2021 L ST NW, SUITE 900, WASHINGTON, DC 20036 USA SN 0006-4971 EI 1528-0020 J9 BLOOD JI Blood PD DEC 6 PY 2014 VL 124 IS 21 PG 3 WC Hematology SC Hematology GA CA9KQ UT WOS:000349242708130 ER PT J AU Kochenderfer, JN Somerville, R Lu, LL Iwamoto, A Yang, JC Klebanoff, C Kammula, U Sherry, RM Victoria, S Yuan, C Feldman, S Feldman, T Goy, A Morton, KE Toomey, MA Rosenberg, SA AF Kochenderfer, James N. Somerville, Robert Lu, Lily Iwamoto, Alex Yang, James C. Klebanoff, Christopher Kammula, Udai Sherry, Richard M. Victoria, Shi Yuan, Constance Feldman, Steven Feldman, Tatyana Goy, Andre Morton, Kathleen E. Toomey, Mary Ann Rosenberg, Steven A. TI Anti-CD19 CAR T Cells Administered after Low-Dose Chemotherapy Can Induce Remissions of Chemotherapy-Refractory Diffuse Large B-Cell Lymphoma SO BLOOD LA English DT Meeting Abstract C1 [Kochenderfer, James N.; Yang, James C.; Sherry, Richard M.; Feldman, Steven; Morton, Kathleen E.; Toomey, Mary Ann] NCI, Bethesda, MD 20892 USA. [Somerville, Robert; Lu, Lily; Iwamoto, Alex; Klebanoff, Christopher; Kammula, Udai; Rosenberg, Steven A.] NCI, Surg Branch, Bethesda, MD 20892 USA. [Victoria, Shi] NCI, Expt Transplantat & Immunol Branch, Bethesda, MD 20892 USA. [Yuan, Constance] NIH, Bethesda, MD 20892 USA. [Feldman, Tatyana] Hackensack Univ, Med Ctr, Hackensack, NJ USA. [Goy, Andre] Hackensack Univ, Med Ctr, John Theurer Canc Ctr, Hackensack, NJ USA. NR 0 TC 2 Z9 2 U1 0 U2 4 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 2021 L ST NW, SUITE 900, WASHINGTON, DC 20036 USA SN 0006-4971 EI 1528-0020 J9 BLOOD JI Blood PD DEC 6 PY 2014 VL 124 IS 21 PG 3 WC Hematology SC Hematology GA CA9KQ UT WOS:000349242704143 ER PT J AU Kotlyar, D Petrovas, C Cooper, A Ambrozak, D Annunziata, C Hernandez, L Yamamoto, T Ferrando-Martinez, S Casazza, J Koup, R AF Kotlyar, David Petrovas, Constantinos Cooper, Arik Ambrozak, David Annunziata, Christina Hernandez, Lidia Yamamoto, Takuya Ferrando-Martinez, Sara Casazza, Joseph Koup, Richard TI Potential Synergy of TRAIL with CDK9 Inhibition in Selective Killing of HIV Infected Cell Lines and Primary CD4+T Cells SO BLOOD LA English DT Meeting Abstract C1 [Kotlyar, David; Petrovas, Constantinos; Cooper, Arik; Ambrozak, David; Annunziata, Christina; Hernandez, Lidia; Yamamoto, Takuya; Ferrando-Martinez, Sara; Casazza, Joseph; Koup, Richard] NIH, Bethesda, MD 20892 USA. RI Annunziata, Christina/L-3219-2016 OI Annunziata, Christina/0000-0003-2033-6532 NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 2021 L ST NW, SUITE 900, WASHINGTON, DC 20036 USA SN 0006-4971 EI 1528-0020 J9 BLOOD JI Blood PD DEC 6 PY 2014 VL 124 IS 21 PG 4 WC Hematology SC Hematology GA CA9KQ UT WOS:000349242702031 ER PT J AU Lai, C Cole, D Lucas, N Steinberg, SM Widemann, BC Dunleavy, K Wilson, WH AF Lai, Catherine Cole, Diane Lucas, Nicole Steinberg, Seth M. Widemann, Brigitte C. Dunleavy, Kieron Wilson, Wyndham H. TI Pharmacokinetics and Tolerability of Etoposide in Newly Diagnosed Lymphoma Patients with Hepatic Impairment SO BLOOD LA English DT Meeting Abstract C1 [Lai, Catherine; Lucas, Nicole] NCI, NIH, Bethesda, MD 20892 USA. [Cole, Diane; Widemann, Brigitte C.; Dunleavy, Kieron] NIH, Bethesda, MD 20892 USA. [Steinberg, Seth M.] NCI, Bethesda, MD 20892 USA. [Wilson, Wyndham H.] NCI, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 2021 L ST NW, SUITE 900, WASHINGTON, DC 20036 USA SN 0006-4971 EI 1528-0020 J9 BLOOD JI Blood PD DEC 6 PY 2014 VL 124 IS 21 PG 3 WC Hematology SC Hematology GA CA9KQ UT WOS:000349242705077 ER PT J AU Le, RQ Tian, X Jain, NA Lu, K Ito, S Draper, DA Anandi, P Hourigan, CS Dunavin, N Barrett, J Battiwalla, M AF Le, Robert Q. Tian, Xin Jain, Natasha A. Lu, Kit Ito, Sawa Draper, Debbie A. Anandi, Prathima Hourigan, Christopher S. Dunavin, Neil Barrett, John Battiwalla, Minoo TI Clinical Comorbidity Measures and Predictive Scores in Ex Vivo T Cell Depleted Allogeneic Hematopoietic Stem Cell Transplantation SO BLOOD LA English DT Meeting Abstract C1 [Le, Robert Q.; Jain, Natasha A.; Lu, Kit; Ito, Sawa; Draper, Debbie A.; Anandi, Prathima; Hourigan, Christopher S.; Dunavin, Neil; Barrett, John; Battiwalla, Minoo] NHLBI, Hematol Branch, NIH, Bethesda, MD 20892 USA. [Tian, Xin] NHLBI, Off Biostat Res, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 2021 L ST NW, SUITE 900, WASHINGTON, DC 20036 USA SN 0006-4971 EI 1528-0020 J9 BLOOD JI Blood PD DEC 6 PY 2014 VL 124 IS 21 PG 3 WC Hematology SC Hematology GA CA9KQ UT WOS:000349242705153 ER PT J AU Lei, HY Li, TW Tsai, S Biggar, RJ Nkrumah, F Neequayee, J Gutierrez, M Epelman, S Lo, SC Mbulaiteye, SM Bhatia, K AF Lei, Haiyan Li, Tianwei Tsai, Shien Biggar, Robert J. Nkrumah, Francis Neequayee, Janet Gutierrez, Marina Epelman, Sidnei Lo, Shyh-Ching Mbulaiteye, Sam M. Bhatia, Kishor TI Whole Genome Sequences of Epstein-Barr Viruses Associated with Burkitt Lymphoma Tissues SO BLOOD LA English DT Meeting Abstract C1 [Lei, Haiyan; Li, Tianwei; Tsai, Shien; Lo, Shyh-Ching] US FDA, Bethesda, MD 20014 USA. [Biggar, Robert J.] Queensland Univ Technol, Brisbane, Qld 4001, Australia. [Nkrumah, Francis] Noguchi Mem Inst, Accra, Ghana. [Neequayee, Janet] Univ Ghana, Accra, Ghana. [Gutierrez, Marina] Lab Stamboulian, Buenos Aires, DF, Argentina. [Epelman, Sidnei] St Marcelina Hosp, Sao Paulo, Brazil. [Mbulaiteye, Sam M.; Bhatia, Kishor] NCI, Div Canc Epidemiol & Genet, NIH, Rockville, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 4 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 2021 L ST NW, SUITE 900, WASHINGTON, DC 20036 USA SN 0006-4971 EI 1528-0020 J9 BLOOD JI Blood PD DEC 6 PY 2014 VL 124 IS 21 PG 3 WC Hematology SC Hematology GA CA9KQ UT WOS:000349242706051 ER PT J AU Meier, ER Byrnes, C Lee, YT Weissman, M Miller, JL AF Meier, Emily R. Byrnes, Colleen Lee, Y. Terry Weissman, Maxine Miller, Jeffery L. TI Absolute Reticulocyte Count Is Negatively Correlated with Fetal Hemoglobin during Infancy and Early Childhood in Patients with Sickle Cell Anemia SO BLOOD LA English DT Meeting Abstract C1 [Meier, Emily R.] Childrens Natl Med Ctr, Div Hematol, Washington, DC 20010 USA. [Meier, Emily R.; Byrnes, Colleen; Lee, Y. Terry; Miller, Jeffery L.] NIDDK, NIH, Bethesda, MD 20892 USA. [Weissman, Maxine] NIH, Ctr Clin, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 2021 L ST NW, SUITE 900, WASHINGTON, DC 20036 USA SN 0006-4971 EI 1528-0020 J9 BLOOD JI Blood PD DEC 6 PY 2014 VL 124 IS 21 PG 3 WC Hematology SC Hematology GA CA9KQ UT WOS:000349242703172 ER PT J AU Minniti, CP Baird, JH Xu, DH Mendelsohn, L Saiyed, R Jackson, M Nichols, J Kim-Shapiro, D Xia, Y Kato, GJ AF Minniti, Caterina P. Baird, John H. Xu, Dihua Mendelsohn, Laurel Saiyed, Rehan Jackson, Mary Nichols, James Kim-Shapiro, Daniel Xia, Yang Kato, Gregory J. TI End-Alveolar Carbon Monoxide As a Measure of Erythrocyte Survival and Hemolytic Severity in Sickle Cell Disease SO BLOOD LA English DT Meeting Abstract C1 [Minniti, Caterina P.; Baird, John H.; Mendelsohn, Laurel; Saiyed, Rehan; Nichols, James] NHLBI, Bethesda, MD 20892 USA. [Minniti, Caterina P.] NHLBI, NIH, Bethesda, MD 20892 USA. [Xu, Dihua; Jackson, Mary] NIH, Bethesda, MD 20892 USA. [Kim-Shapiro, Daniel] Wake Forest Univ, Winston Salem, NC 27109 USA. [Xia, Yang] Univ Texas Med Sch Houston, Houston, TX USA. [Kato, Gregory J.] Univ Pittsburgh, Pittsburgh, PA USA. RI Kato, Gregory/I-7615-2014 OI Kato, Gregory/0000-0003-4465-3217 NR 0 TC 0 Z9 0 U1 0 U2 2 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 2021 L ST NW, SUITE 900, WASHINGTON, DC 20036 USA SN 0006-4971 EI 1528-0020 J9 BLOOD JI Blood PD DEC 6 PY 2014 VL 124 IS 21 PG 3 WC Hematology SC Hematology GA CA9KQ UT WOS:000349242702073 ER PT J AU Muranski, P Franco-Colon, M Chinnasamy, D Chen, K Stegemann, S Sui, J Ito, S Sabatino, M Stroncek, DF Palmore, T Kolls, J Barrett, AJ AF Muranski, Pawel Franco-Colon, Manuel Chinnasamy, Dhanalakshmi Chen, Kong Stegemann, Scott Sui, Jinwen Ito, Sawa Sabatino, Marianna Stroncek, David F. Palmore, Tara Kolls, Jay Barrett, A. John TI Ex Vivo Generation of CD4(+) Th17 Cells to Prevent and Treat Infection from Antibiotic-Resistant Klebsiella Pneumoniae in Immunocompromised Patients SO BLOOD LA English DT Meeting Abstract C1 [Muranski, Pawel; Franco-Colon, Manuel; Chinnasamy, Dhanalakshmi; Stegemann, Scott; Sui, Jinwen; Barrett, A. John] NHLBI, Hematol Branch, NIH, Bethesda, MD 20892 USA. [Chen, Kong; Kolls, Jay] Univ Pittsburgh, Sch Med, Pittsburgh, PA USA. [Ito, Sawa] NHLBI, NIH, Bethesda, MD 20892 USA. [Sabatino, Marianna] NIH, Bethesda, MD 20892 USA. [Stroncek, David F.] NIH, Ctr Clin, Bethesda, MD 20892 USA. [Palmore, Tara] NIAID, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 2021 L ST NW, SUITE 900, WASHINGTON, DC 20036 USA SN 0006-4971 EI 1528-0020 J9 BLOOD JI Blood PD DEC 6 PY 2014 VL 124 IS 21 PG 3 WC Hematology SC Hematology GA CA9KQ UT WOS:000349242704087 ER PT J AU Nakagawa, M Schmitz, R Xiao, WM Goldman, CK Xu, WH Yang, YD Waldmann, TA Staudt, LM AF Nakagawa, Masao Schmitz, Roland Xiao, Wenming Goldman, Carolyn K. Xu, Weihong Yang, Yandan Waldmann, Thomas A. Staudt, Louis M. TI A Gain-of-Function CCR4 Mutations in Adult T-Cell Leukemia/Lymphoma (ATLL) Enhance the Chemotactic Abilities and PI3K/AKT Activation SO BLOOD LA English DT Meeting Abstract C1 [Nakagawa, Masao; Xiao, Wenming; Goldman, Carolyn K.; Xu, Weihong; Yang, Yandan] NIH, Bethesda, MD 20892 USA. [Schmitz, Roland] NCI, Bethesda, MD 20892 USA. [Waldmann, Thomas A.] NCI, NIH, Bethesda, MD 20892 USA. [Staudt, Louis M.] NCI, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 2021 L ST NW, SUITE 900, WASHINGTON, DC 20036 USA SN 0006-4971 EI 1528-0020 J9 BLOOD JI Blood PD DEC 6 PY 2014 VL 124 IS 21 PG 3 WC Hematology SC Hematology GA CA9KQ UT WOS:000349242702109 ER PT J AU Nakata, Y Ueda, T Nagamachi, A Wolff, L Seishi, O Inaba, T Honda, H AF Nakata, Yuichiro Ueda, Takeshi Nagamachi, Akiko Wolff, Linda Seishi, Ogawa Inaba, Toshiya Honda, Hiroaki TI Generation and Analysis of a Novel Mouse Model for Chronic Myelomonocytic Leukemia (CMML) with Acquired Expression of c-CBLQ367P SO BLOOD LA English DT Meeting Abstract C1 [Nakata, Yuichiro; Ueda, Takeshi; Nagamachi, Akiko; Inaba, Toshiya; Honda, Hiroaki] Hiroshima Univ, Hiroshima, Japan. [Wolff, Linda] NCI, NIH, Bethesda, MD 20892 USA. [Seishi, Ogawa] Kyoto Univ, Kyoto, Japan. NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 2021 L ST NW, SUITE 900, WASHINGTON, DC 20036 USA SN 0006-4971 EI 1528-0020 J9 BLOOD JI Blood PD DEC 6 PY 2014 VL 124 IS 21 PG 3 WC Hematology SC Hematology GA CA9KQ UT WOS:000349242705204 ER PT J AU O'Brien, KA Anderson, SM Farrar, J Vlachos, A Atsidaftos, E Lipton, JM Ellis, SR Bodine, DM AF O'Brien, Kelly A. Anderson, Stacie M. Farrar, Jason Vlachos, Adrianna Atsidaftos, Eva Lipton, Jeffrey Michael Ellis, Steven R. Bodine, David M. TI In Vitro Analysis of Erythroid Cells Derived from the Culture of Diamond Blackfan Anemia Patient CD34+Cells SO BLOOD LA English DT Meeting Abstract C1 [O'Brien, Kelly A.; Bodine, David M.] NHGRI, Genet & Mol Biol Branch, Bethesda, MD 20892 USA. [Anderson, Stacie M.] Flow Cytometry Core, Bethesda, MD USA. [Farrar, Jason] Univ Arkansas Med Sci, Little Rock, AR 72205 USA. [Vlachos, Adrianna; Atsidaftos, Eva; Lipton, Jeffrey Michael] Hofstra North Shore LIJ Sch Med, Feinstein Inst Med Res, Steven & Alexandra Cohen Childrens Med Ctr, New Hyde Pk, NY USA. [Ellis, Steven R.] Univ Louisville, Sch Med, Louisville, KY 40292 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 2021 L ST NW, SUITE 900, WASHINGTON, DC 20036 USA SN 0006-4971 EI 1528-0020 J9 BLOOD JI Blood PD DEC 6 PY 2014 VL 124 IS 21 PG 3 WC Hematology SC Hematology GA CA9KQ UT WOS:000349242701059 ER PT J AU Osnos, L Sheikh, V Hahn, J Perez-Diez, A Sereti, I Maric, I AF Osnos, Leah Sheikh, Virginia Hahn, Jamie Perez-Diez, Ainhoa Sereti, Irini Maric, Irina TI Administration of rhIL-7 Is Associated with Increase in Precursor T-Cells in Bone Marrows of Patients with Idiopathic CD4 Lymphocytopenia SO BLOOD LA English DT Meeting Abstract C1 [Osnos, Leah; Sheikh, Virginia; Perez-Diez, Ainhoa; Sereti, Irini] NIAID, Bethesda, MD 20892 USA. [Hahn, Jamie] NIH, Dept Lab Med, Ctr Clin, Bethesda, MD 20892 USA. [Maric, Irina] NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 2021 L ST NW, SUITE 900, WASHINGTON, DC 20036 USA SN 0006-4971 EI 1528-0020 J9 BLOOD JI Blood PD DEC 6 PY 2014 VL 124 IS 21 PG 3 WC Hematology SC Hematology GA CA9KQ UT WOS:000349242702194 ER PT J AU Polizzotto, MN Sereti, I Uldrick, TS Wyvill, KM Jensen, SMR Singh, A Kovacs, SB Aleman, KO Marshall, V Whitby, D Maldarelli, F Steinberg, SM Zeldis, JB Yarchoan, R AF Polizzotto, Mark N. Sereti, Irini Uldrick, Thomas S. Wyvill, Kathleen M. Jensen, Stig M. R. Singh, Amrit Kovacs, Stephen B. Aleman, Karen O. Marshall, Vickie Whitby, Denise Maldarelli, Frank Steinberg, Seth M. Zeldis, Jerome B. Yarchoan, Robert TI Pomalidomide Induces Expansion of Activated and Central Memory CD4+and CD8+T Cells in Vivo in Patients with and without HIV Infection SO BLOOD LA English DT Meeting Abstract C1 [Polizzotto, Mark N.; Uldrick, Thomas S.; Wyvill, Kathleen M.; Aleman, Karen O.; Maldarelli, Frank; Steinberg, Seth M.; Yarchoan, Robert] NCI, Bethesda, MD 20892 USA. [Sereti, Irini; Jensen, Stig M. R.; Singh, Amrit; Kovacs, Stephen B.] NIAID, Bethesda, MD 20892 USA. [Marshall, Vickie; Whitby, Denise] Frederick Natl Lab Canc Res, Frederick, MD USA. [Zeldis, Jerome B.] Celgene Corp, Summit, NJ USA. NR 0 TC 0 Z9 0 U1 1 U2 2 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 2021 L ST NW, SUITE 900, WASHINGTON, DC 20036 USA SN 0006-4971 EI 1528-0020 J9 BLOOD JI Blood PD DEC 6 PY 2014 VL 124 IS 21 PG 3 WC Hematology SC Hematology GA CA9KQ UT WOS:000349242702070 ER PT J AU Porter, DL Lacey, SF Hwang, WT Shaw, P Frey, NV Chew, A Chen, F Kalos, M Gonzalez, V Marcucci, KT Maude, SL Melenhorst, JJ Litchman, M Teachey, DT Shen, A Quintas-Cardamas, A Wood, PA Levine, BL June, CH Grupp, SA AF Porter, David L. Lacey, Simon F. Hwang, Wei-Ting Shaw, Pamela Frey, Noelle V. Chew, Anne Chen, Fang Kalos, Michael Gonzalez, Vanessa Marcucci, Katherine T. Maude, Shannon L. Melenhorst, Jan J. Litchman, Manuel Teachey, David T. Shen, Angela Quintas-Cardamas, Alfonso Wood, Patricia A. Levine, Bruce L. June, Carl H. Grupp, Stephan A. TI Cytokine Release Syndrome (CRS) after Chimeric Antigen Receptor (CAR) T Cell Therapy for Relapsed/Refractory (R/R) CLL SO BLOOD LA English DT Meeting Abstract C1 [Porter, David L.; Lacey, Simon F.; Chen, Fang; Kalos, Michael; Gonzalez, Vanessa; Marcucci, Katherine T.; Litchman, Manuel; June, Carl H.] Univ Penn, Philadelphia, PA 19104 USA. [Hwang, Wei-Ting] Univ Penn, Sch Med, Philadelphia, PA 19104 USA. [Shaw, Pamela; Chew, Anne; Levine, Bruce L.] Univ Penn, Perelman Sch Med, Philadelphia, PA 19104 USA. [Frey, Noelle V.] Univ Penn, Abramson Canc Ctr, Philadelphia, PA 19104 USA. [Maude, Shannon L.; Teachey, David T.; Grupp, Stephan A.] Childrens Hosp Philadelphia, Philadelphia, PA 19104 USA. [Melenhorst, Jan J.] NHLBI, Hematol Branch, NIH, Bethesda, MD 20892 USA. [Litchman, Manuel] Novartis, E Hanover, NJ USA. [Shen, Angela; Wood, Patricia A.] Novartis Pharmaceut, E Hanover, NJ USA. [Quintas-Cardamas, Alfonso] Novartis Pharmaceut, E Hanover, NJ USA. NR 0 TC 0 Z9 0 U1 2 U2 4 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 2021 L ST NW, SUITE 900, WASHINGTON, DC 20036 USA SN 0006-4971 EI 1528-0020 J9 BLOOD JI Blood PD DEC 6 PY 2014 VL 124 IS 21 PG 3 WC Hematology SC Hematology GA CA9KQ UT WOS:000349242704076 ER PT J AU Prasad, PK Landry, I Keegan, THM Harlan, L Parsons, H Lynch, CF Wilder-Smith, A Hamilton, AS Wu, XC AF Prasad, Pinki K. Landry, Ian Keegan, Theresa H. M. Harlan, Lynne Parsons, Helen Lynch, Charles F. Wilder-Smith, Ashley Hamilton, Ann S. Wu, Xiao-Cheng TI Healthcare Services Needs and Co-Morbidity Assessment Among Adolescents and Young Adults with Cancer: the AYA Hope Study SO BLOOD LA English DT Meeting Abstract C1 [Prasad, Pinki K.] LSUSHC, Childrens Hosp New Orleans, New Orleans, LA USA. [Landry, Ian; Wu, Xiao-Cheng] LSUSHC, New Orleans, LA USA. [Keegan, Theresa H. M.] Canc Prevent Inst Calif, Fremont, CA USA. [Harlan, Lynne; Wilder-Smith, Ashley] NIH, Bethesda, MD 20892 USA. [Parsons, Helen] UTHSCSA, San Antonio, TX USA. [Lynch, Charles F.] Univ Iowa, Iowa City, IA USA. [Hamilton, Ann S.] Univ So Calif, Norris Canc Ctr, Los Angeles, CA USA. NR 0 TC 0 Z9 0 U1 1 U2 2 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 2021 L ST NW, SUITE 900, WASHINGTON, DC 20036 USA SN 0006-4971 EI 1528-0020 J9 BLOOD JI Blood PD DEC 6 PY 2014 VL 124 IS 21 PG 3 WC Hematology SC Hematology GA CA9KQ UT WOS:000349242700168 ER PT J AU Pulsipher, MA Logan, BR Kiefer, DM Chitphakdithai, P Switzer, GE Riches, ML Rizzo, JD Anderlini, P Leitman, SF Varni, JW Hays, A Kobusingye, H Besser, RM Miller, JP Drexler, RJ King, RJ Horowitz, MM Navarro, WH Confer, DL AF Pulsipher, Michael A. Logan, Brent R. Kiefer, Deidre M. Chitphakdithai, Pintip Switzer, Galen E. Riches, Marcie L. Rizzo, J. Douglas Anderlini, Paolo Leitman, Susan F. Varni, James W. Hays, Amy Kobusingye, Hati Besser, RaeAnne M. Miller, John P. Drexler, Rebecca J. King, Roberta J. Horowitz, Mary M. Navarro, Willis H. Confer, Dennis L. TI Baseline Symptoms, Female Sex, and Younger Age Are Correlated with Higher Levels of Peri-Collection Pain, Symptoms, and Persistent Discomfort One Year after Related Donor BM and PBSC Donation: An Analysis of the Related Donor Safety Study (RDSafe) SO BLOOD LA English DT Meeting Abstract C1 [Pulsipher, Michael A.] Univ Utah, Sch Med, Salt Lake City, UT USA. [Logan, Brent R.; Rizzo, J. Douglas; Horowitz, Mary M.] Med Coll Wisconsin, Milwaukee, WI 53226 USA. [Kiefer, Deidre M.; Chitphakdithai, Pintip; Hays, Amy; Kobusingye, Hati; Besser, RaeAnne M.; Miller, John P.; Drexler, Rebecca J.; King, Roberta J.; Navarro, Willis H.; Confer, Dennis L.] Natl Marrow Donor Program, Minneapolis, MN USA. [Switzer, Galen E.] Univ Pittsburgh, Pittsburgh, PA USA. [Riches, Marcie L.] H Lee Moffitt Canc Ctr & Res Inst, Tampa, FL USA. [Anderlini, Paolo] Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA. [Leitman, Susan F.] NIH, Bethesda, MD 20892 USA. [Varni, James W.] Texas A&M Univ, College Stn, TX USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 2021 L ST NW, SUITE 900, WASHINGTON, DC 20036 USA SN 0006-4971 EI 1528-0020 J9 BLOOD JI Blood PD DEC 6 PY 2014 VL 124 IS 21 PG 4 WC Hematology SC Hematology GA CA9KQ UT WOS:000349242707185 ER PT J AU Purev, E Tian, X Pantin, JM Reger, RN Cook, L Ramos, C Cho, E Purvey, S Prince, P Khuu, H Stroncek, D Leitman, S Townsley, DM Young, NS Aue, G Childs, RW AF Purev, Enkhtsetseg Tian, Xin Pantin, Jeremy M. Reger, Robert N. Cook, Lisa Ramos, Catalina Cho, Elena Purvey, Sneha Prince, Patricia Khuu, Hahn Stroncek, David Leitman, Susan Townsley, Danielle M. Young, Neal S. Aue, Georg Childs, Richard W. TI Excellent Engraftment and Reduced Acute and Chronic Graft Versus Host Disease (GVHD) in ATG-Refractory Severe Aplastic Anemia (SAA) Following Transplantation of a PBSC Allograft Containing CD34+Selected Cells Combined with Non-Mobilized Donor T-Cells SO BLOOD LA English DT Meeting Abstract C1 [Purev, Enkhtsetseg; Tian, Xin; Reger, Robert N.; Cook, Lisa; Ramos, Catalina; Cho, Elena; Prince, Patricia; Khuu, Hahn; Stroncek, David; Leitman, Susan; Young, Neal S.; Aue, Georg; Childs, Richard W.] NIH, Bethesda, MD 20892 USA. [Pantin, Jeremy M.] Georgia Regents Univ, Ctr Canc, Augusta, GA USA. [Purvey, Sneha] MedStar Washington Hosp Ctr, Washington, DC USA. [Townsley, Danielle M.] NHLBI, Hematol Branch, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 2021 L ST NW, SUITE 900, WASHINGTON, DC 20036 USA SN 0006-4971 EI 1528-0020 J9 BLOOD JI Blood PD DEC 6 PY 2014 VL 124 IS 21 PG 3 WC Hematology SC Hematology GA CA9KQ UT WOS:000349242701136 ER PT J AU Rand, KA Song, C Hwang, AE Huff, CA Bernal-Mizrachi, L Tomasson, MH Ailawadhi, S Van Den Berg, DJ Sheng, X Graff, JJ Conti, DV Zimmerman, T Peters, E Singhal, S Bock, CH Pawlish, K Colditz, GA Sheng, X Stram, A Strom, SS Rybicki, B Kittles, R Terebelo, H Stanford, J Goodman, PJ Berndt, SI Carpten, J Hennis, AJ Chu, LS Casey, G Driver, WR Klein, EA Leske, MC John, E Murphy, AB Neslund-Dudas, C Stevens, VL Pettaway, C Zheng, W Wu, SY Witte, J Zheng, SL Xu, JF Munshi, NC Hsing, A Ingles, S Mehta, J Signorello, LB Chanock, SJ Nemesure, B Mohrbacher, AM Janakiraman, N Blot, WJ Henderson, BE Kolonel, LN Anderson, KC Chiu, BCH Zonder, J Orlowski, RZ Lonial, S Stram, DO Haiman, C Cozen, W AF Rand, Kristin A. Song, Chi Hwang, Amie E. Huff, Carol A. Bernal-Mizrachi, Leon Tomasson, Michael H. Ailawadhi, Sikander Van Den Berg, David J. Sheng, Xin Graff, John J. Conti, David V. Zimmerman, Todd Peters, Edward Singhal, Seema Bock, Cathryn H. Pawlish, Karen Colditz, Graham A. Sheng, Xin Stram, Alexander Strom, Sara S. Rybicki, Benjamin Kittles, Rick Terebelo, Howard Stanford, Janet Goodman, Phyllis J. Berndt, Sonja I. Carpten, John Hennis, Anselm Jm Chu, Lisa Casey, Graham Driver, W. R. Klein, Eric A. Leske, M. Christina John, Esther Murphy, Adam Bryant Neslund-Dudas, Christine Stevens, Victoria L. Pettaway, Curtis Zheng, Wei Wu, Suh-Yuh Witte, John Zheng, Siqun Lilly Xu, Jianfeng Munshi, Nikhil C. Hsing, Ann Ingles, Sue Mehta, Jayesh Signorello, Lisa B. Chanock, Stephen Jacob Nemesure, Barbara Mohrbacher, Ann M. Janakiraman, Nalini Blot, William J. Henderson, Brian E. Kolonel, Laurence N. Anderson, Kenneth C. Chiu, Brian C-H Zonder, Jeffrey Orlowski, Robert Z. Lonial, Sagar Stram, Daniel O. Haiman, Christopher Cozen, Wendy TI Genetic Susceptibility Markers of Multiple Myeloma in African-Americans SO BLOOD LA English DT Meeting Abstract C1 [Rand, Kristin A.; Hwang, Amie E.; Conti, David V.; Mohrbacher, Ann M.; Henderson, Brian E.; Haiman, Christopher] Univ So Calif, USC Keck Sch Med, Los Angeles, CA USA. [Song, Chi; Sheng, Xin; Sheng, Xin; Ingles, Sue; Stram, Daniel O.; Cozen, Wendy] Univ So Calif, Keck Sch Med, Los Angeles, CA 90033 USA. [Hwang, Amie E.; Van Den Berg, David J.] Univ So Calif, Norris Canc Ctr, Los Angeles, CA USA. [Huff, Carol A.] Johns Hopkins Univ, Baltimore, MD USA. [Bernal-Mizrachi, Leon] Emory Univ, Sch Med, Atlanta, GA USA. [Tomasson, Michael H.; Colditz, Graham A.] Washington Univ, Sch Med, St Louis, MO USA. [Ailawadhi, Sikander] Mayo Clin, Jacksonville, FL 32224 USA. [Graff, John J.] Univ Med & Dent New Jersey, Robert Wood Johnson Med Sch, Canc Inst New Jersey, New Brunswick, NJ USA. [Zimmerman, Todd] Univ Chicago Med, Chicago, IL USA. [Peters, Edward] Louisiana State Univ, Sch Publ Hlth, New Orleans, LA USA. [Singhal, Seema] Northwestern Univ, Feinberg Sch Med, Chicago, IL 60611 USA. [Bock, Cathryn H.] Wayne State Univ, Sch Med, Karmanos Canc Inst, Detroit, MI USA. [Pawlish, Karen] New Jersey Dept Hlth & Senior Serv, Trenton, NJ USA. [Stram, Alexander; Casey, Graham; Witte, John] Univ So Calif, Keck Sch Med, Norris Comprehens Ctr, Los Angeles, CA 90033 USA. [Pettaway, Curtis; Orlowski, Robert Z.] Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA. [Rybicki, Benjamin; Murphy, Adam Bryant; Janakiraman, Nalini] Henry Ford Hosp, Detroit, MI 48202 USA. [Kittles, Rick] Univ Arizona, Tucson, AZ USA. [Terebelo, Howard] Providence Canc Inst, Southfield, MI USA. [Stanford, Janet; Goodman, Phyllis J.] Univ Washington, Seattle, WA 98195 USA. [Berndt, Sonja I.] NCI, NIH, Bethesda, MD 20892 USA. [Carpten, John] Translat Genom Res Inst, Phoenix, AZ USA. [Hennis, Anselm Jm] Univ W Indies, Bridgetown, Barbados. [Chu, Lisa; John, Esther; Hsing, Ann] Canc Prevent Inst Calif, Fremont, CA USA. [Driver, W. R.; Stevens, Victoria L.] Amer Canc Soc, Atlanta, GA 30329 USA. Cleveland Clin, Cleveland, OH 44106 USA. [Leske, M. Christina] SUNY Stony Brook, Med Ctr, Stony Brook, NY 11794 USA. [Murphy, Adam Bryant; Mehta, Jayesh] Northwestern Univ, Chicago, IL 60611 USA. [Neslund-Dudas, Christine] Henry Ford Hlth Syst, Detroit, MI USA. [Zheng, Wei] Vanderbilt Univ, Sch Med, Nashville, TN 37212 USA. [Wu, Suh-Yuh; Nemesure, Barbara] SUNY Stony Brook, Stony Brook, NY 11794 USA. Univ Calif San Francisco, San Francisco, CA 94143 USA. [Zheng, Siqun Lilly] Wake Forest Sch Med, Winston Salem, NC USA. [Xu, Jianfeng] Wake Forest Sch Med, Salem Winston, NC USA. [Munshi, Nikhil C.; Anderson, Kenneth C.] Harvard Univ, Sch Med, LeBow Inst Myeloma Therapeut, Boston, MA USA. [Munshi, Nikhil C.; Anderson, Kenneth C.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Jerome Lipper Myeloma Ctr,Dept Med Oncol, Boston, MA 02115 USA. [Signorello, Lisa B.] Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA. [Chanock, Stephen Jacob] NCI, NIH, US Dept Human Hlth Serv, Rockville, MD USA. [Blot, William J.] Vanderbilt Univ, Sch Med, Vanderbilt Epidemiol Ctr, Nashville, TN 37212 USA. [Kolonel, Laurence N.] Univ Hawaii, Ctr Canc, Honolulu, HI 96822 USA. [Chiu, Brian C-H] Univ Chicago, Chicago, IL 60637 USA. [Zonder, Jeffrey] Karmanos Canc Inst, Detroit, MI USA. [Lonial, Sagar] Emory Univ, Winship Canc Inst, Atlanta, GA 30322 USA. NR 0 TC 0 Z9 0 U1 2 U2 3 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 2021 L ST NW, SUITE 900, WASHINGTON, DC 20036 USA SN 0006-4971 EI 1528-0020 J9 BLOOD JI Blood PD DEC 6 PY 2014 VL 124 IS 21 PG 4 WC Hematology SC Hematology GA CA9KQ UT WOS:000349242702025 ER PT J AU Rawstron, A Fazi, C Villamor, N Delgado, J Letestu, R Cymbalista, F Palacio, C Bosch, F De Tute, RM Liptrot, S O'Brien, D Spacek, M Dobber, J Kater, AP Gambell, PC Westerman, DA Soosapilla, A Mulligan, SP Lozanski, G Lin, K Pettitt, AR Brachtl, G Egle, A Williamson, DW Sanders, CM Robins, H Boysen, J Shanafelt, TD Hanson, CA Jorgensen, JL Wierda, WG Yuan, C Stetler-Stevenson, M Rassenti, L Broome, HE Kipps, TJ Hauwel, M Marinov, I Craig, FE Josep, N Moreno, C Stehlikova, O Doubek, M Pospisilova, S Kreuzer, KA Hallek, M Hillmen, P Montserrat, E Ghia, P AF Rawstron, Andy Fazi, Claudia Villamor, Neus Delgado, Julio Letestu, Remi Cymbalista, Florence Palacio, Carlos Bosch, Francesc De Tute, Ruth M. Liptrot, Stuart O'Brien, David Spacek, Martin Dobber, Johan Kater, Arnon P. Gambell, Peter C. Westerman, David A. Soosapilla, Asha Mulligan, Stephen P. Lozanski, Gerard Lin, Ke Pettitt, Andrew R. Brachtl, Gabi Egle, Alexander Williamson, David W. Sanders, Catherine M. Robins, Harlan Boysen, Justin Shanafelt, Tait D. Hanson, Curtis A. Jorgensen, Jeffrey L. Wierda, William G. Yuan, Constance Stetler-Stevenson, Maryalice Rassenti, Laura Broome, H. Elizabeth Kipps, Thomas J. Hauwel, Mathieu Marinov, Iuri Craig, Fiona E. Josep, Nomdedeu Moreno, Carol Stehlikova, Olga Doubek, Michael Pospisilova, Sarka Kreuzer, Karl-Anton Hallek, Michael Hillmen, Peter Montserrat, Emili Ghia, Paolo TI A Complementary Role of High Throughput Sequencing and Multiparameter Cytometry for Minimal Residual Disease (MRD) Detection in Chronic Lymphocytic Leukemia (CLL):an European Research Initiative (ERIC) Study SO BLOOD LA English DT Meeting Abstract C1 [Rawstron, Andy; De Tute, Ruth M.] St Jamess Inst Oncol, Leeds, W Yorkshire, England. [Fazi, Claudia] IRCCS San Raffaele Sci Inst, Milan, Italy. [Villamor, Neus] Hosp Clin Barcelona, IDIBAPS, Barcelona, Spain. [Delgado, Julio; Montserrat, Emili] Univ Barcelona, IDIBAPS, Hosp Clin, Inst Hematol & Oncol,Dept Hematol, Barcelona, Spain. [Letestu, Remi] Hop Avicenne, F-93009 Bobigny, France. [Cymbalista, Florence] Hop Avicenne, AP HP, F-93009 Bobigny, France. [Palacio, Carlos] Hosp Univ Vall dHebron, Barcelona, Spain. [Bosch, Francesc] Hosp Valle De Hebron, Barcelona, Spain. [Liptrot, Stuart; O'Brien, David] St James Hosp, Dublin 8, Ireland. [Spacek, Martin] Gen Univ Hosp, Prague, Czech Republic. [Dobber, Johan; Kater, Arnon P.] Univ Amsterdam, Acad Med Ctr, NL-1105 AZ Amsterdam, Netherlands. [Gambell, Peter C.; Westerman, David A.] Peter MacCallum Canc Ctr, Melbourne, Vic, Australia. [Soosapilla, Asha] Laverty Pathol, Sydney, NSW, Australia. [Mulligan, Stephen P.] Royal N Shore Hosp, Sydney, NSW, Australia. [Lozanski, Gerard] Ohio State Univ, Med Ctr, Columbus, OH 43210 USA. [Lin, Ke] Royal Liverpool & Broadgreen Univ Hosp NHS Trust, Dept Haematol, Liverpool, Merseyside, England. [Pettitt, Andrew R.] Royal Liverpool & Broadgreen Univ Hosp NHS Trust, Liverpool, Merseyside, England. [Brachtl, Gabi] Paracelsus Med Univ, Salzburg, Austria. [Egle, Alexander] Paracelsus Med Univ, Dept Internal Med 3, Salzburg, Austria. [Williamson, David W.; Sanders, Catherine M.; Robins, Harlan] Adapt Biotechnol, Seattle, WA USA. [Boysen, Justin; Shanafelt, Tait D.; Hanson, Curtis A.] Mayo Clin, Rochester, MN USA. [Jorgensen, Jeffrey L.; Wierda, William G.] Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA. [Yuan, Constance] NIH, Bethesda, MD 20892 USA. [Stetler-Stevenson, Maryalice] NCI, NIH, Bethesda, MD 20892 USA. [Rassenti, Laura; Kipps, Thomas J.] Univ Calif San Diego, La Jolla, CA 92093 USA. [Broome, H. Elizabeth] Moores UCSD Canc Ctr, La Jolla, CA USA. [Hauwel, Mathieu] Univ Hosp Geneva, Geneva, Switzerland. [Marinov, Iuri] Inst Hematol & Blood Transfus, CR-12820 Prague, Czech Republic. [Craig, Fiona E.] Univ Pittsburgh, Pittsburgh, PA USA. [Josep, Nomdedeu] Hosp Santa Creu & Sant Pau, Barcelona, Spain. [Moreno, Carol] Hosp Santa Creu & Sant Pau, Barcelona, Spain. [Stehlikova, Olga] Univ Hosp, Brno, Czech Republic. [Doubek, Michael; Pospisilova, Sarka] Univ Hosp Brno, Brno, Czech Republic. [Doubek, Michael] Med Fac MU, Brno, Czech Republic. [Kreuzer, Karl-Anton] Univ Cologne, D-50931 Cologne, Germany. [Hallek, Michael] Univ Hosp, Cologne, Germany. [Hillmen, Peter] St James Univ Hosp, Leeds, W Yorkshire, England. [Ghia, Paolo] Univ Vita Salute San Raffaele, Milan, Italy. RI Delgado, Julio/D-4891-2013 OI Delgado, Julio/0000-0002-5157-4376 NR 0 TC 0 Z9 0 U1 0 U2 4 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 2021 L ST NW, SUITE 900, WASHINGTON, DC 20036 USA SN 0006-4971 EI 1528-0020 J9 BLOOD JI Blood PD DEC 6 PY 2014 VL 124 IS 21 PG 4 WC Hematology SC Hematology GA CA9KQ UT WOS:000349242704119 ER PT J AU Ruella, M Barrett, D Kenderian, SS Shestova, O Hofmann, TJ Scholler, J Lacey, SF Melenhorst, JJ Nazimuddin, F Kalos, M Porter, DL June, CH Grupp, SA Gill, SI AF Ruella, Marco Barrett, David Kenderian, Saad S. Shestova, Olga Hofmann, Ted J. Scholler, John Lacey, Simon F. Melenhorst, Jan J. Nazimuddin, Farzana Kalos, Michael Porter, David L. June, Carl H. Grupp, Stephan A. Gill, Saar I. TI Novel Chimeric Antigen Receptor T Cells for the Treatment of CD19-Negative Relapses Occurring after CD19-Targeted Immunotherapies SO BLOOD LA English DT Meeting Abstract C1 [Ruella, Marco; Kenderian, Saad S.; Shestova, Olga; Scholler, John; Lacey, Simon F.; Nazimuddin, Farzana; Kalos, Michael; Porter, David L.; June, Carl H.; Gill, Saar I.] Univ Penn, Philadelphia, PA 19104 USA. [Barrett, David; Hofmann, Ted J.; Grupp, Stephan A.] Childrens Hosp Philadelphia, Philadelphia, PA 19104 USA. [Kenderian, Saad S.] Mayo Clin, Rochester, MN USA. [Melenhorst, Jan J.] NHLBI, Hematol Branch, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 2021 L ST NW, SUITE 900, WASHINGTON, DC 20036 USA SN 0006-4971 EI 1528-0020 J9 BLOOD JI Blood PD DEC 6 PY 2014 VL 124 IS 21 PG 4 WC Hematology SC Hematology GA CA9KQ UT WOS:000349242704063 ER PT J AU Scott, DW Wright, GW Williams, M Lih, J Jaffe, ES Rosenwald, A Campo, E Chan, WC Connors, JM Smeland, E Braziel, RM Ott, G Delabie, J Weisenburger, DD Cook, JR Greiner, TC Fu, K Walsh, W Gascoyne, RD Staudt, LM Rimsza, LM AF Scott, David W. Wright, George W. Williams, Mickey Lih, Jason Jaffe, Elaine S. Rosenwald, Andreas Campo, Elias Chan, Wing (John) C. Connors, Joseph M. Smeland, Erlend Braziel, Rita M. Ott, German Delabie, Jan Weisenburger, Dennis D. Cook, James R. Greiner, Timothy C. Fu, Kai Walsh, William Gascoyne, Randy D. Staudt, Louis M. Rimsza, Lisa M. TI Accurate Diagnosis of Aggressive B Cell Non-Hodgkin Lymphomas Using Gene Expression Profiling of Formalin-Fixed, Paraffin-Embedded Tissues SO BLOOD LA English DT Meeting Abstract C1 [Scott, David W.] British Columbia Canc Agcy, Vancouver, BC V5Z 4E6, Canada. [Wright, George W.; Jaffe, Elaine S.] NCI, Bethesda, MD 20892 USA. [Williams, Mickey; Lih, Jason; Walsh, William] SAIC Frederick Natl Lab Canc Res, Frederick, MD USA. [Rosenwald, Andreas] Univ Wurzburg, D-97070 Wurzburg, Germany. [Campo, Elias] Hosp Clin IDIBAPS, Barcelona, Spain. [Chan, Wing (John) C.] City Hope Natl Med Ctr, Los Angeles, CA USA. [Connors, Joseph M.] British Columbia Canc Agcy, Ctr Lymphoid Canc, Vancouver, BC V5Z 4E6, Canada. [Connors, Joseph M.] Univ British Columbia, Vancouver, BC V5Z 1M9, Canada. [Smeland, Erlend] Univ Olso, Oslo, Norway. [Braziel, Rita M.] Oregon Hlth & Sci Univ, Portland, OR 97201 USA. [Ott, German] Robert Bosch Krankenhaus, Stuttgart, Germany. [Ott, German] Dr Margarete Fischer Bosch Inst Clin Pharmacol, Stuttgart, Germany. [Delabie, Jan] Oslo Univ Hosp, Oslo, Norway. [Weisenburger, Dennis D.] City Hope Natl Med Ctr, Duarte, CA 91010 USA. [Cook, James R.] Cleveland Clin Fdn, Cleveland, OH 44195 USA. [Greiner, Timothy C.; Fu, Kai] Univ Nebraska Med Ctr, Omaha, NE USA. [Gascoyne, Randy D.] Ctr Lymphoid Canc, Vancouver, BC, Canada. [Staudt, Louis M.] NCI, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. [Rimsza, Lisa M.] Univ Arizona, Tucson, AZ USA. NR 0 TC 0 Z9 0 U1 1 U2 5 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 2021 L ST NW, SUITE 900, WASHINGTON, DC 20036 USA SN 0006-4971 EI 1528-0020 J9 BLOOD JI Blood PD DEC 6 PY 2014 VL 124 IS 21 PG 4 WC Hematology SC Hematology GA CA9KQ UT WOS:000349242708051 ER PT J AU Sood, RB Hansen, NF Donovan, FX Carrington, B Maskeri, B Young, A Bucci, D Chandrasekharaappa, S Mullikin, JC Bloomfield, CD Marcucci, G Liu, P AF Sood, Raman B. Hansen, Nancy F. Donovan, Frank X. Carrington, Blake Maskeri, Baishali Young, Alice Bucci, Donna Chandrasekharaappa, Settara Mullikin, James C. Bloomfield, Clara D. Marcucci, Guido Liu, Paul TI Somatic Mutational Landscape of AML with Inv(16) and t(8;21) Identifies Two Distinct Patterns in Relapse Tumors SO BLOOD LA English DT Meeting Abstract C1 [Sood, Raman B.; Hansen, Nancy F.; Donovan, Frank X.; Carrington, Blake; Maskeri, Baishali; Young, Alice; Chandrasekharaappa, Settara; Mullikin, James C.; Liu, Paul] NIH, Bethesda, MD 20892 USA. [Bucci, Donna; Bloomfield, Clara D.; Marcucci, Guido] Ohio State Univ, Columbus, OH 43210 USA. NR 0 TC 0 Z9 0 U1 1 U2 2 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 2021 L ST NW, SUITE 900, WASHINGTON, DC 20036 USA SN 0006-4971 EI 1528-0020 J9 BLOOD JI Blood PD DEC 6 PY 2014 VL 124 IS 21 PG 2 WC Hematology SC Hematology GA CA9KQ UT WOS:000349242702208 ER PT J AU Swaminathan, S Klemm, L Park, E Ford, AM Kweon, SM Trageser, D Hasselfeld, B Henke, N Geng, HM Schwarz, K Casellas, R Schatz, DG Lieber, MR Papaemmanuil, E Greaves, M Muschen, M AF Swaminathan, Srividya Klemm, Lars Park, Eugene Ford, Anthony M. Kweon, Soo-mi Trageser, Daniel Hasselfeld, Brian Henke, Nadine Geng, Huimin Schwarz, Klaus Casellas, Rafael Schatz, David G. Lieber, Michael R. Papaemmanuil, Elli Greaves, Mel Muschen, Markus TI Mechanisms of Clonal Evolution of Pre-Leukemic Clones in Childhood Pre-B Acute Lymphoblastic Leukemia SO BLOOD LA English DT Meeting Abstract C1 [Swaminathan, Srividya; Klemm, Lars; Park, Eugene; Geng, Huimin; Muschen, Markus] Univ Calif San Francisco, San Francisco, CA 94143 USA. [Park, Eugene; Papaemmanuil, Elli; Muschen, Markus] Univ Cambridge, Cambridge, England. [Ford, Anthony M.; Greaves, Mel] Inst Canc Res, London SW3 6JB, England. [Kweon, Soo-mi; Trageser, Daniel; Hasselfeld, Brian; Lieber, Michael R.] Univ So Calif, Los Angeles, CA USA. [Henke, Nadine] Univ Dusseldorf, Dusseldorf, Germany. [Schwarz, Klaus] Univ Ulm, D-89069 Ulm, Germany. [Casellas, Rafael] NIAMS, Bethesda, MD USA. [Schatz, David G.] Yale Univ, New Haven, CT USA. NR 0 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 0006-4971 EI 1528-0020 J9 BLOOD JI Blood PD DEC 6 PY 2014 VL 124 IS 21 PG 3 WC Hematology SC Hematology GA CA9KQ UT WOS:000349242705195 ER PT J AU Tristan, SM Peer, CJ Korde, N Nehal, L Sham, M Landgren, O Figg, WD AF Tristan, Sissung M. Peer, Cody J. Korde, Neha Nehal, Lakhani Sham, Malinkody Landgren, Ola Figg, William D. TI Plasma Protease-Mediated Metabolism of Carfilzomib and Its Implications on Clinical Effects and Side Effects SO BLOOD LA English DT Meeting Abstract C1 [Tristan, Sissung M.] Off Clin Director, Clin Pharmacol Program, Bethesda, MD USA. [Peer, Cody J.; Sham, Malinkody; Figg, William D.] NCI, Bethesda, MD 20892 USA. [Korde, Neha; Landgren, Ola] Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. [Nehal, Lakhani] Mem Sloan Kettering, New York, NY USA. RI Figg Sr, William/M-2411-2016 NR 0 TC 0 Z9 0 U1 1 U2 2 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 2021 L ST NW, SUITE 900, WASHINGTON, DC 20036 USA SN 0006-4971 EI 1528-0020 J9 BLOOD JI Blood PD DEC 6 PY 2014 VL 124 IS 21 PG 3 WC Hematology SC Hematology GA CA9KQ UT WOS:000349242705091 ER PT J AU Uldrick, TS Bhutani, M Polizzotto, MN Aleman, KO Wyvill, KM Goncalves, PH Pittaluga, S Filie, A Marshall, V Rupert, AW Tosato, G Whitby, D Little, RF Steinberg, SM Yarchoan, R AF Uldrick, Thomas S. Bhutani, Manisha Polizzotto, Mark N. Aleman, Karen O. Wyvill, Kathleen M. Goncalves, Priscila H. Pittaluga, Stefania Filie, Armando Marshall, Vickie Rupert, Adam W. Tosato, Giovanna Whitby, Denise Little, Richard F. Steinberg, Seth M. Yarchoan, Robert TI Inflammatory Cytokines, Hyperferritinemia and IgE Are Prognostic in Patients with KSHV-Associated Lymphomas Treated with Curative Intent Therapy SO BLOOD LA English DT Meeting Abstract C1 [Uldrick, Thomas S.; Bhutani, Manisha; Polizzotto, Mark N.; Aleman, Karen O.; Wyvill, Kathleen M.; Goncalves, Priscila H.; Filie, Armando; Tosato, Giovanna; Steinberg, Seth M.; Yarchoan, Robert] NIH, Bethesda, MD 20892 USA. [Pittaluga, Stefania] NCI, NIH, Bethesda, MD 20892 USA. [Marshall, Vickie; Whitby, Denise] Frederick Natl Lab Canc Res, Frederick, MD USA. [Rupert, Adam W.] Leidos Biomed Res Inc, Frederick, MD USA. [Little, Richard F.] NCI, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 2 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 2021 L ST NW, SUITE 900, WASHINGTON, DC 20036 USA SN 0006-4971 EI 1528-0020 J9 BLOOD JI Blood PD DEC 6 PY 2014 VL 124 IS 21 PG 4 WC Hematology SC Hematology GA CA9KQ UT WOS:000349242708141 ER PT J AU van Beers, EJ Yang, YQ Raghavachari, N Tian, X Allen, D Nichols, JS Mendelsohn, L Nekhai, SA Gordeuk, VR Taylor, JG Kato, GJ AF van Beers, Eduard J. Yang, Yanqin Raghavachari, Nalini Tian, Xin Allen, Darlene Nichols, James S. Mendelsohn, Laurel Nekhai, Sergei A. Gordeuk, Victor R. Taylor, James G. Kato, Gregory J. TI Iron, Expression of the Pattern Recognition Receptor-Inflammasome System, and Early Death in Adults with Sickle Cell Disease SO BLOOD LA English DT Meeting Abstract C1 [van Beers, Eduard J.; Tian, Xin; Nichols, James S.; Mendelsohn, Laurel] NHLBI, Bethesda, MD 20892 USA. [van Beers, Eduard J.] Univ Med Ctr Utrecht, Utrecht, Netherlands. [Yang, Yanqin; Allen, Darlene] NHLBI, NIH, Bethesda, MD 20892 USA. [Raghavachari, Nalini] NIH, Bethesda, MD 20892 USA. [Nekhai, Sergei A.] Howard Univ, Washington, DC 20059 USA. [Gordeuk, Victor R.] Univ Illinois, Chicago, IL USA. [Taylor, James G.] NHLBI, Genom Med Sect, Hematol Branch, NIH, Bethesda, MD 20892 USA. [Kato, Gregory J.] Univ Pittsburgh, Pittsburgh, PA USA. RI Kato, Gregory/I-7615-2014 OI Kato, Gregory/0000-0003-4465-3217 NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 2021 L ST NW, SUITE 900, WASHINGTON, DC 20036 USA SN 0006-4971 EI 1528-0020 J9 BLOOD JI Blood PD DEC 6 PY 2014 VL 124 IS 21 PG 4 WC Hematology SC Hematology GA CA9KQ UT WOS:000349242707089 ER PT J AU Vaughan, K Diaw, L Wang, ZY Liu, CH Barr, M Darbari, D Woodhouse, KA Allen, D Quinn, M Seamon, C Klings, ES Raghavachari, N Taylor, JG AF Vaughan, Kathleen Diaw, Lena Wang Zhengyuan Liu, Chia-Hao Barr, Marci Darbari, Deepika Woodhouse, Kimberley A. Allen, Darlene Quinn, Meghan Seamon, Catherine Klings, Elizabeth S. Raghavachari, Nalini Taylor, James G. TI Comparative Clinical and Gene Expression Analysis of Sickle Cell Anemia and Hemoglobin SC Disease SO BLOOD LA English DT Meeting Abstract C1 [Vaughan, Kathleen; Diaw, Lena; Wang Zhengyuan; Liu, Chia-Hao; Woodhouse, Kimberley A.; Quinn, Meghan; Seamon, Catherine] NHLBI, Genom Med Sect, Hematol Branch, Bethesda, MD 20892 USA. [Barr, Marci; Darbari, Deepika; Allen, Darlene] NHLBI, NIH, Bethesda, MD 20892 USA. [Darbari, Deepika] NHLBI, Childrens Natl Med Ctr, Bethesda, MD 20892 USA. [Klings, Elizabeth S.] Boston Univ, Sch Med, Boston, MA 02118 USA. [Raghavachari, Nalini] NHLBI, Genom Core Facil, NIH, Bethesda, MD 20892 USA. [Taylor, James G.] NHLBI, Genom Med Sect, Hematol Branch, NIH, Bethesda, MD 20892 USA. NR 0 TC 1 Z9 1 U1 0 U2 1 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 2021 L ST NW, SUITE 900, WASHINGTON, DC 20036 USA SN 0006-4971 EI 1528-0020 J9 BLOOD JI Blood PD DEC 6 PY 2014 VL 124 IS 21 PG 3 WC Hematology SC Hematology GA CA9KQ UT WOS:000349242706208 ER PT J AU Wang, XD Mendelsohn, L Freeman, L Vaisman, B Remaley, A Kato, GJ AF Wang, Xunde Mendelsohn, Laurel Freeman, Lita Vaisman, Boris Remaley, Alan Kato, Gregory J. TI Stimulation of Nitric Oxide Synthase Activity By Plasma Apolipoproteins: a Biomarker of Endothelial Function in Adults with Sickle Cell Disease SO BLOOD LA English DT Meeting Abstract C1 [Wang, Xunde; Mendelsohn, Laurel; Remaley, Alan] NHLBI, Bethesda, MD 20892 USA. [Freeman, Lita] NHLBI, NIH, Bethesda, MD 20892 USA. [Vaisman, Boris] NIH, Bethesda, MD 20892 USA. [Kato, Gregory J.] Univ Pittsburgh, Pittsburgh, PA USA. RI Kato, Gregory/I-7615-2014 OI Kato, Gregory/0000-0003-4465-3217 NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 2021 L ST NW, SUITE 900, WASHINGTON, DC 20036 USA SN 0006-4971 EI 1528-0020 J9 BLOOD JI Blood PD DEC 6 PY 2014 VL 124 IS 21 PG 3 WC Hematology SC Hematology GA CA9KQ UT WOS:000349242703007 ER PT J AU Wang, XD Callacondo, D Rojas, J Quesada-Olarte, J Remaley, AT Maric, I Tisdale, JF Leon-Velarde, F Villafuerte, F Hsieh, M AF Wang, Xunde Callacondo, David Rojas, Jose Quesada-Olarte, Jose Remaley, Alan T. Maric, Irina Tisdale, John F. Leon-Velarde, Fabiola Villafuerte, Francisco Hsieh, Matthew TI Erythrocytosis in Chronic Mountain Sickness (CMS) in Andeans SO BLOOD LA English DT Meeting Abstract C1 [Wang, Xunde] NHLBI, Bethesda, MD 20892 USA. [Callacondo, David; Rojas, Jose; Quesada-Olarte, Jose; Leon-Velarde, Fabiola; Villafuerte, Francisco] UPCH, Lima, Peru. [Remaley, Alan T.] NHLBI, NIH, Bethesda, MD 20892 USA. [Maric, Irina] NIH, Bethesda, MD 20892 USA. [Tisdale, John F.; Hsieh, Matthew] NIDDK, NHLBI, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 1 U2 3 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 2021 L ST NW, SUITE 900, WASHINGTON, DC 20036 USA SN 0006-4971 EI 1528-0020 J9 BLOOD JI Blood PD DEC 6 PY 2014 VL 124 IS 21 PG 3 WC Hematology SC Hematology GA CA9KQ UT WOS:000349242700032 ER PT J AU Watts, JM Dumitriu, B Hilden, P Chen, C Rapaport, F Kishtagari, A Ahn, J Devlin, SM Rampal, RK Levine, RL Young, NS Tallman, MS AF Watts, Justin M. Dumitriu, Bogdan Hilden, Patrick Chen, Christina Rapaport, Franck Kishtagari, Ashwin Ahn, Jihae Devlin, Sean M. Rampal, Raajit K. Levine, Ross L. Young, Neal S. Tallman, Martin S. TI Telomere Length Is Associated with Specific Mutations and Mutation Classes in Patients with Acute Myeloid Leukemia SO BLOOD LA English DT Meeting Abstract C1 [Watts, Justin M.; Hilden, Patrick; Rapaport, Franck; Kishtagari, Ashwin; Ahn, Jihae; Devlin, Sean M.; Rampal, Raajit K.; Levine, Ross L.; Tallman, Martin S.] Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. [Watts, Justin M.] Univ Miami, Miller Sch Med, Sylvester Comprehens Canc Ctr, Miami, FL 33136 USA. [Dumitriu, Bogdan; Chen, Christina; Young, Neal S.] NIH, Bethesda, MD 20892 USA. [Kishtagari, Ashwin] Mt Sinai St Lukes Roosevelt Hosp, New York, NY USA. NR 0 TC 1 Z9 1 U1 0 U2 3 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 2021 L ST NW, SUITE 900, WASHINGTON, DC 20036 USA SN 0006-4971 EI 1528-0020 J9 BLOOD JI Blood PD DEC 6 PY 2014 VL 124 IS 21 PG 4 WC Hematology SC Hematology GA CA9KQ UT WOS:000349242705070 ER PT J AU Xu, YL Jiang, L Fang, RR Zhou, JX Morse, H AF Xu, Yulian Jiang, Lei Fang, Rachel R. Zhou, Jeff Xiwu Morse, Herbert TI Loss of IRF8 Inhibits the Growth of Diffuse Large B-Cell Lymphoma SO BLOOD LA English DT Meeting Abstract C1 [Xu, Yulian; Jiang, Lei] Ningbo Univ, Ningbo 315211, Zhejiang, Peoples R China. [Fang, Rachel R.; Zhou, Jeff Xiwu] Ningbo Univ, Sch Med, Ningbo 315211, Zhejiang, Peoples R China. [Morse, Herbert] NIAID, NIH, Rockville, MD USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 2021 L ST NW, SUITE 900, WASHINGTON, DC 20036 USA SN 0006-4971 EI 1528-0020 J9 BLOOD JI Blood PD DEC 6 PY 2014 VL 124 IS 21 PG 3 WC Hematology SC Hematology GA CA9KQ UT WOS:000349242707003 ER PT J AU Alter, BP Giri, N Savage, SA Rosenberg, PS AF Alter, Blanche P. Giri, Neelam Savage, Sharon A. Rosenberg, Philip S. TI Telomere Length in Inherited Bone Marrow Failure Syndromes SO BLOOD LA English DT Meeting Abstract CT 56th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2014 CL San Francisco, CA SP Amer Soc Hematol C1 [Alter, Blanche P.; Rosenberg, Philip S.] NCI, NIH, Rockville, MD USA. [Giri, Neelam; Savage, Sharon A.] NCI, Rockville, MD USA. RI Savage, Sharon/B-9747-2015 OI Savage, Sharon/0000-0001-6006-0740 NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 2021 L ST NW, SUITE 900, WASHINGTON, DC 20036 USA SN 0006-4971 EI 1528-0020 J9 BLOOD JI Blood PD DEC 6 PY 2014 VL 124 IS 21 PG 3 WC Hematology SC Hematology GA CA9HU UT WOS:000349233800059 ER PT J AU Alvarnas, J Le Rademacher, J Wang, Y Little, RF Akpek, G Ayala, E Devine, S Kaplan, L Noy, A Popat, U Thompson, J Horowitz, MH Mendizabal, A Navarro, WH Ambinder, R AF Alvarnas, J. Le Rademacher, J. Wang, Y. Little, Richard F. Akpek, G. Ayala, E. Devine, S. Kaplan, L. Noy, A. Popat, U. Thompson, J. Horowitz, M. H. Mendizabal, A. Navarro, W. H. Ambinder, R. CA BMT CTN AMC TI Autologous Hematopoietic Stem Cell Transplantation (AHCT) in Patients with Chemotherapy-Sensitive, Relapsed/Refractory (CSRR) Human Immunodeficiency Virus (HIV)-Associated Lymphoma (HAL): Results from the Blood and Marrow Transplant Clinical Trials Network (BMT CTN 0803)/AIDS Malignancy Consortium (AMC-071) Trial SO BLOOD LA English DT Meeting Abstract CT 56th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2014 CL San Francisco, CA SP Amer Soc Hematol C1 [Alvarnas, J.] City Hope Natl Med Ctr, Duarte, CA 91010 USA. [Le Rademacher, J.; Horowitz, M. H.] Med Coll Wisconsin, Milwaukee, WI 53226 USA. [Wang, Y.; Thompson, J.; Mendizabal, A.] Emmes Corp, Rockville, MD USA. [Little, Richard F.] NCI, Canc Therapy Evaluat Program, Div Canc Therapy & Diag, Rockville, MD USA. [Akpek, G.] Univ Maryland Med Syst, Greenebaum Canc Ctr, Baltimore, MD USA. [Ayala, E.] Univ S Florida, H Lee Moffitt Canc Ctr, Tampa, FL 33682 USA. [Devine, S.] Ohio State Univ, Arthur G James Canc Ctr Hosp, Columbus, OH 43210 USA. [Kaplan, L.] Univ Calif San Francisco, San Francisco, CA 94143 USA. [Noy, A.] Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. [Popat, U.] Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA. [Navarro, W. H.] Natl Marrow Donor Program, Minneapolis, MN USA. [Ambinder, R.] Johns Hopkins Sch Med, Baltimore, MD USA. [BMT CTN] Blood & Marrow Transplant Clin Trials Network, Duarte, CA USA. [AMC] AIDS Malignancy Consortium, Duarte, CA USA. NR 0 TC 0 Z9 0 U1 0 U2 2 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 2021 L ST NW, SUITE 900, WASHINGTON, DC 20036 USA SN 0006-4971 EI 1528-0020 J9 BLOOD JI Blood PD DEC 6 PY 2014 VL 124 IS 21 PG 4 WC Hematology SC Hematology GA CA9KX UT WOS:000349243502101 ER PT J AU Anand, A Anandi, P Natasha, JA Lu, K Dunavin, N Hourigan, CS Le, RQ Chokshi, PD Ito, S Stroncek, DF Sabatino, M Barrett, J Battiwalla, M AF Anand, Ankit Anandi, Prathima Natasha, Jain A. Lu, Kit Dunavin, Neil Hourigan, Christopher S. Le, Robert Q. Chokshi, Puja D. Ito, Sawa Stroncek, David F. Sabatino, Marianna Barrett, John Battiwalla, Minoo TI CD34+Selection Avoids Methotrexate and Reduces the Severity of Oral Mucositis in TBI-Based Allogeneic Stem Cell Transplantation SO BLOOD LA English DT Meeting Abstract CT 56th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2014 CL San Francisco, CA SP Amer Soc Hematol C1 [Anand, Ankit; Anandi, Prathima; Natasha, Jain A.; Lu, Kit; Dunavin, Neil; Hourigan, Christopher S.; Le, Robert Q.; Chokshi, Puja D.; Ito, Sawa; Barrett, John; Battiwalla, Minoo] NHLBI, Hematol Branch, NIH, Bethesda, MD 20892 USA. [Stroncek, David F.; Sabatino, Marianna] NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 2021 L ST NW, SUITE 900, WASHINGTON, DC 20036 USA SN 0006-4971 EI 1528-0020 J9 BLOOD JI Blood PD DEC 6 PY 2014 VL 124 IS 21 PG 2 WC Hematology SC Hematology GA CA9KX UT WOS:000349243500111 ER PT J AU Arons, E Still, K Davies, S Zhou, H Kreitman, RJ AF Arons, Evgeny Still, Katherine Davies, Sarah Zhou, Hong Kreitman, Robert J. TI Minimal Residual Disease By Patient-Specific Taqman Real Time PCR in Newly Diagnosed Hairy Cell Leukemia Patients Randomized to Initial Vs Delayed Rituximab in Combination with Cladribine SO BLOOD LA English DT Meeting Abstract CT 56th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2014 CL San Francisco, CA SP Amer Soc Hematol C1 [Arons, Evgeny; Still, Katherine; Davies, Sarah; Zhou, Hong; Kreitman, Robert J.] NCI, NIH, Bethesda, MD 20892 USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 2021 L ST NW, SUITE 900, WASHINGTON, DC 20036 USA SN 0006-4971 EI 1528-0020 J9 BLOOD JI Blood PD DEC 6 PY 2014 VL 124 IS 21 PG 3 WC Hematology SC Hematology GA CA9KX UT WOS:000349243504118 ER PT J AU Baljevic, M Dumitriu, B Lee, JW Paietta, E Racevskis, J Chen, C Stein, EM Gallagher, RE Rowe, JM Appelbaum, FR Powell, BL Larson, RA Young, NS Tallman, MS AF Baljevic, Muhamed Dumitriu, Bogdan Lee, Ju-Whei Paietta, Elisabeth Racevskis, Janis Chen, Christina Stein, Eytan M. Gallagher, Robert E. Rowe, Jacob M. Appelbaum, Frederick R. Powell, Bayard L. Larson, Richard A. Young, Neal S. Tallman, Martin S. TI Telomere Length Recovery Strongly Predicts Overall Survival in Acute Promyelocytic Leukemia SO BLOOD LA English DT Meeting Abstract CT 56th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2014 CL San Francisco, CA SP Amer Soc Hematol C1 [Baljevic, Muhamed] Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA. [Dumitriu, Bogdan; Chen, Christina; Young, Neal S.] NIH, Bethesda, MD 20892 USA. [Lee, Ju-Whei] Dana Farber Canc Inst, Boston, MA 02115 USA. [Paietta, Elisabeth] Montefiore Med Ctr, North Div, Bronx, NY 10467 USA. [Racevskis, Janis] 4Montefiore Med Ctr, Albert Einstein Coll Med, Bronx, NY USA. [Stein, Eytan M.; Tallman, Martin S.] Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. [Gallagher, Robert E.] Albert Einstein Coll Med, Bronx, NY 10467 USA. [Rowe, Jacob M.] Shaare Zedek Med Ctr, Jerusalem, Israel. [Appelbaum, Frederick R.] Fred Hutchinson Canc Res Ctr, Seattle, WA 98104 USA. [Powell, Bayard L.] Wake Forest Univ, Ctr Comprehens Canc, Winston Salem, NC 27109 USA. [Larson, Richard A.] Univ Chicago, Chicago, IL 60637 USA. NR 0 TC 0 Z9 0 U1 0 U2 2 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 2021 L ST NW, SUITE 900, WASHINGTON, DC 20036 USA SN 0006-4971 EI 1528-0020 J9 BLOOD JI Blood PD DEC 6 PY 2014 VL 124 IS 21 PG 3 WC Hematology SC Hematology GA CA9HU UT WOS:000349233804117 ER PT J AU Bjorklund, AT Carlsten, M Schaffer, M Liu, L Cooley, SA Miller, JS Watz, E Palma, M Hansson, L Wahlin, BE Mollgard, L Hagglund, H Blomberg, P Ljungman, PT Hellstrom-Lindberg, E Ljunggren, HG Malmberg, KJ AF Bjorklund, Andreas T. Carlsten, Mattias Schaffer, Marie Liu, Lisa Cooley, Sarah A. Miller, Jeffrey S. Watz, Emma Palma, Marzia Hansson, Lotta Wahlin, Bjorn E. Mollgard, Lars Hagglund, Hans Blomberg, Pontus Ljungman, Per T. Hellstrom-Lindberg, Eva Ljunggren, Hans-Gustaf Malmberg, Karl-Johan TI Early and Transient Microchimerism Associated with Complete Remission after Adoptively Transferred Haploidentical NK Cells Against High Risk Myelodysplastic Syndrome and Refractory Acute Myeloid Leukemia SO BLOOD LA English DT Meeting Abstract CT 56th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2014 CL San Francisco, CA SP Amer Soc Hematol C1 [Bjorklund, Andreas T.; Liu, Lisa; Palma, Marzia; Hansson, Lotta; Wahlin, Bjorn E.; Ljungman, Per T.; Ljunggren, Hans-Gustaf; Malmberg, Karl-Johan] Karolinska Inst, Stockholm, Sweden. [Carlsten, Mattias] NHLBI, NIH, Bethesda, MD 20892 USA. [Schaffer, Marie; Palma, Marzia; Hansson, Lotta; Blomberg, Pontus; Ljungman, Per T.] Karolinska Univ Hosp, Stockholm, Sweden. [Cooley, Sarah A.; Miller, Jeffrey S.] Univ Minnesota, Minneapolis, MN USA. [Watz, Emma] Karolinska Univ Hosp, Huddinge, Sweden. [Mollgard, Lars] Sahlgrens Univ Hosp, Gothenburg, Sweden. [Hagglund, Hans] Akad Sjukhuset, Uppsala, Sweden. [Hellstrom-Lindberg, Eva] Karolinska Inst, Karolinska Univ Hosp Huddinge, Ctr Hematol & Regenerat Med, Dept Med, Stockholm, Sweden. [Malmberg, Karl-Johan] Oslo Univ Hosp, Oslo, Norway. NR 0 TC 0 Z9 0 U1 0 U2 2 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 2021 L ST NW, SUITE 900, WASHINGTON, DC 20036 USA SN 0006-4971 EI 1528-0020 J9 BLOOD JI Blood PD DEC 6 PY 2014 VL 124 IS 21 PG 3 WC Hematology SC Hematology GA CA9KX UT WOS:000349243500076 ER PT J AU Branvall, E Smedby, KE Rosner, BA Giovannucci, E Glossmann, JP Bertrand, KA Chen, H Laden, F Zhang, S Birmann, BM AF Branvall, Elsa Smedby, Karin E. Rosner, Bernard A. Giovannucci, Edward Glossmann, Jan-Peter Bertrand, Kimberly A. Chen, Honglei Laden, Francine Zhang, Shumin Birmann, Brenda M. TI Regular Aspirin Use and Risk of Non-Hodgkin Lymphoma: A Prospective Analysis in the Nurses' Health Study SO BLOOD LA English DT Meeting Abstract CT 56th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2014 CL San Francisco, CA SP Amer Soc Hematol C1 [Branvall, Elsa; Smedby, Karin E.] Karolinska Univ Hosp, Stockholm, Sweden. [Branvall, Elsa] Karolinska Inst, Stockholm, Sweden. [Rosner, Bernard A.; Giovannucci, Edward; Bertrand, Kimberly A.; Laden, Francine; Zhang, Shumin; Birmann, Brenda M.] Brigham & Womens Hosp, Boston, MA 02115 USA. [Rosner, Bernard A.; Giovannucci, Edward; Bertrand, Kimberly A.; Laden, Francine; Zhang, Shumin; Birmann, Brenda M.] Harvard Univ, Sch Med, Boston, MA USA. [Rosner, Bernard A.; Giovannucci, Edward; Bertrand, Kimberly A.; Laden, Francine] Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA. [Glossmann, Jan-Peter] Univ Hosp Cologne, Cologne, Germany. [Chen, Honglei] NIH, Res Triangle Pk, NC USA. [Zhang, Shumin] Takeda Pharmaceut Int Inc, Deerfield, IL USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 2021 L ST NW, SUITE 900, WASHINGTON, DC 20036 USA SN 0006-4971 EI 1528-0020 J9 BLOOD JI Blood PD DEC 6 PY 2014 VL 124 IS 21 PG 3 WC Hematology SC Hematology GA CA9HU UT WOS:000349233808168 ER PT J AU Brissot, E Ito, S Lu, K Cantilena, C Smith, BD Prince, G Sadrzadeh, H Fathi, AT Strickland, SA Hensel, NF Chinian, F Keyvanfar, K Battiwalla, M Muranski, P Hourigan, CS Barrett, J AF Brissot, Eolia Ito, Sawa Lu, Kit Cantilena, Carly Smith, B. Douglas Prince, Gabrielle Sadrzadeh, Hossein Fathi, Amir T. Strickland, Stephen A. Hensel, Nancy F. Chinian, Fariba Keyvanfar, Keyvan Battiwalla, Minoo Muranski, Pawel Hourigan, Christopher S. Barrett, John TI T Cell Exhaustion and Downregulation of Cytotoxic NK Cells - an Immune Escape Mechanism in Adult Acute Lymphoblastic Leukemia SO BLOOD LA English DT Meeting Abstract CT 56th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2014 CL San Francisco, CA SP Amer Soc Hematol C1 [Brissot, Eolia] NHLBI, NIH, Bethesda, MD 20892 USA. [Ito, Sawa; Lu, Kit; Keyvanfar, Keyvan; Battiwalla, Minoo; Muranski, Pawel; Hourigan, Christopher S.; Barrett, John] NHLBI, Hematol Branch, NIH, Bethesda, MD 20892 USA. [Cantilena, Carly] NHLBI, Hematol Branch, Bethesda, MD 20892 USA. [Smith, B. Douglas; Prince, Gabrielle] Sidney Kimmel Comprehens Canc Ctr Johns Hopkins, Baltimore, MD USA. [Sadrzadeh, Hossein; Fathi, Amir T.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Canc, Boston, MA USA. [Strickland, Stephen A.] Vanderbilt Univ, Med Ctr, Nashville, TN USA. [Hensel, Nancy F.; Chinian, Fariba] NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 2021 L ST NW, SUITE 900, WASHINGTON, DC 20036 USA SN 0006-4971 EI 1528-0020 J9 BLOOD JI Blood PD DEC 6 PY 2014 VL 124 IS 21 PG 3 WC Hematology SC Hematology GA CA9KX UT WOS:000349243507203 ER PT J AU Carlsten, M Li, LH Su, S Berg, M Reger, R Peshwa, MV Childs, R AF Carlsten, Mattias Li, Linhong Su, Su Berg, Maria Reger, Robert Peshwa, Madhusudan V. Childs, Richard TI Clinical-Grade mRNA Electroporation of NK Cells: A Novel and Highly Efficient Method to Genetically Reprogram Human NK Cells for Cancer Immunotherapy SO BLOOD LA English DT Meeting Abstract CT 56th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2014 CL San Francisco, CA SP Amer Soc Hematol C1 [Carlsten, Mattias; Su, Su; Berg, Maria; Reger, Robert; Childs, Richard] NHLBI, NIH, Bethesda, MD 20892 USA. [Li, Linhong; Peshwa, Madhusudan V.] MaxCyte Inc, Gaithersburg, MD USA. NR 0 TC 0 Z9 0 U1 1 U2 6 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 2021 L ST NW, SUITE 900, WASHINGTON, DC 20036 USA SN 0006-4971 EI 1528-0020 J9 BLOOD JI Blood PD DEC 6 PY 2014 VL 124 IS 21 PG 3 WC Hematology SC Hematology GA CA9HU UT WOS:000349233800090 ER PT J AU Castillo, PA Melenhorst, JJ Hanley, PJ Keller, M Krance, RA Margolin, J Leen, A Heslop, HE Barrett, J Rooney, CM Bollard, CM AF Castillo, Paul A. Melenhorst, Jan J. Hanley, Patrick J. Keller, Michael Krance, Robert A. Margolin, Judith Leen, Ann Heslop, Helen E. Barrett, John Rooney, Cliona M. Bollard, Catherine M. TI Graft Versus Leukemia Response without Graft Versus Host Disease Elicited By Adoptively Transferred Multivirus-Specific T-Cells SO BLOOD LA English DT Meeting Abstract CT 56th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2014 CL San Francisco, CA SP Amer Soc Hematol C1 [Castillo, Paul A.; Krance, Robert A.; Margolin, Judith; Leen, Ann; Heslop, Helen E.; Rooney, Cliona M.; Bollard, Catherine M.] Texas Childrens Hosp, Baylor Coll Med, Ctr Cell & Gene Therapy, Houston, TX 77030 USA. [Castillo, Paul A.; Krance, Robert A.; Margolin, Judith; Leen, Ann; Heslop, Helen E.; Rooney, Cliona M.; Bollard, Catherine M.] Houston Methodist Hosp, Houston, TX USA. [Melenhorst, Jan J.; Barrett, John] NHLBI, Hematol Branch, NIH, Bethesda, MD 20892 USA. [Melenhorst, Jan J.] Univ Penn, Perelman Sch Med, Translat Res Program, Philadelphia, PA 19104 USA. [Hanley, Patrick J.; Keller, Michael; Bollard, Catherine M.] Childrens Natl Hlth Syst, Program Cell Enhancement & Technol Immunotherapy, Sheikh Zayed Inst Pediat Surg Innovat, Washington, DC USA. [Hanley, Patrick J.; Keller, Michael; Bollard, Catherine M.] Childrens Natl Hlth Syst, Ctr Canc & Immunol Res, Washington, DC USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 2021 L ST NW, SUITE 900, WASHINGTON, DC 20036 USA SN 0006-4971 EI 1528-0020 J9 BLOOD JI Blood PD DEC 6 PY 2014 VL 124 IS 21 PG 3 WC Hematology SC Hematology GA CA9HU UT WOS:000349233803093 ER PT J AU Chen, ZS Shojaee, S Geng, HM Lee, JW Buchner, M Klemm, L Lowell, CA Paietta, E Willman, CL Carroll, WL Melnick, A Jung, JU Jumaa, H Coligan, JE Bolland, S Mak, TW Muschen, M AF Chen, Zhengshan Shojaee, Seyedmehdi Geng, Huimin Lee, Jae-Woong Buchner, Maike Klemm, Lars Lowell, Clifford A. Paietta, Elisabeth Willman, Cheryl L. Carroll, William L. Melnick, Ari Jung, Jae U. Jumaa, Hassan Coligan, John E. Bolland, Silvia Mak, Tak W. Muschen, Markus TI Harnessing Negative B Cell Selection to Overcome Drug-Resistance in Acute Lymphoblastic Leukemia SO BLOOD LA English DT Meeting Abstract CT 56th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2014 CL San Francisco, CA SP Amer Soc Hematol C1 [Chen, Zhengshan; Shojaee, Seyedmehdi; Geng, Huimin; Lee, Jae-Woong; Buchner, Maike; Klemm, Lars; Lowell, Clifford A.; Muschen, Markus] Univ Calif San Francisco, San Francisco, CA 94143 USA. [Paietta, Elisabeth] Albert Einsten Coll Med, Bronx, NY USA. [Willman, Cheryl L.] Univ New Mexico, Albuquerque, NM 87131 USA. [Carroll, William L.] NYU, New York, NY USA. [Melnick, Ari] Weill Cornell Med Coll, New York, NY USA. [Jung, Jae U.] Univ So Calif, Los Angeles, CA USA. [Jumaa, Hassan] Max Planck Inst Immunobiol, Freiburg, Germany. [Coligan, John E.] NIH, Rockville, MD USA. [Bolland, Silvia] NIAID, NIH, Rockville, MD USA. [Mak, Tak W.] Ontario Canc Inst, Univ Hlth Network, Campbell Family Inst Breast Canc Res, Toronto, ON M4X 1K9, Canada. NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 2021 L ST NW, SUITE 900, WASHINGTON, DC 20036 USA SN 0006-4971 EI 1528-0020 J9 BLOOD JI Blood PD DEC 6 PY 2014 VL 124 IS 21 PG 3 WC Hematology SC Hematology GA CA9HU UT WOS:000349233806211 ER PT J AU Corat, MAF Metais, JY Dunbar, CE AF Corat, Marcus A. F. Metais, Jean-Yves Dunbar, Cynthia E. TI Progress Towards Creation of a Rhesus Macaque Animal Model for PNH Disease Via Crispr/Cas9 Technology to Knock out the PIG-a Gene SO BLOOD LA English DT Meeting Abstract CT 56th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2014 CL San Francisco, CA SP Amer Soc Hematol C1 [Corat, Marcus A. F.; Metais, Jean-Yves; Dunbar, Cynthia E.] NIH, Bethesda, MD 20892 USA. [Corat, Marcus A. F.] Univ Estadual Campinas, Campinas, SP, Brazil. NR 0 TC 0 Z9 0 U1 2 U2 10 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 2021 L ST NW, SUITE 900, WASHINGTON, DC 20036 USA SN 0006-4971 EI 1528-0020 J9 BLOOD JI Blood PD DEC 6 PY 2014 VL 124 IS 21 PG 3 WC Hematology SC Hematology GA CA9HU UT WOS:000349233806002 ER PT J AU Czuczman, MS Davies, A Linton, KM Wagner-Johnston, N Gascoyne, RD Eberhard, DA Salles, G Witzig, TE Zinzani, PL Wright, GW Staudt, LM Repici, J Song, D Manzke, O Lewis, ID AF Czuczman, Myron S. Davies, Andrew Linton, Kim M. Wagner-Johnston, Nina Gascoyne, Randy D. Eberhard, David A. Salles, Gilles Witzig, Thomas E. Zinzani, Pier Luigi Wright, George W. Staudt, Louis M. Repici, Jacqueline Song, Dale Manzke, Oliver Lewis, Ian D. TI A Phase 2/3 Multicenter, Randomized Study Comparing the Efficacy and Safety of Lenalidomide Versus Investigator's Choice in Relapsed/Refractory DLBCL SO BLOOD LA English DT Meeting Abstract CT 56th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2014 CL San Francisco, CA SP Amer Soc Hematol C1 [Czuczman, Myron S.] Roswell Pk Canc Inst, Buffalo, NY 14263 USA. [Davies, Andrew] Univ Southampton, Canc Sci Div, Southampton, Hants, England. [Linton, Kim M.] Univ Manchester, Manchester, Lancs, England. [Linton, Kim M.] Christie NHS Fdn Trust, Manchester, Lancs, England. [Wagner-Johnston, Nina] Washington Univ, Sch Med, Siteman Canc Ctr, St Louis, MO USA. [Gascoyne, Randy D.] Ctr Lymphoid Canc, Vancouver, BC, Canada. [Eberhard, David A.] Univ N Carolina, Sch Med, Chapel Hill, NC USA. [Salles, Gilles] Ctr Hosp Lyon Sud, Pierre Benite, France. [Witzig, Thomas E.] Mayo Clin, Rochester, MN USA. [Zinzani, Pier Luigi] Inst Hematol & Med Oncol, Bologna, Italy. [Wright, George W.] NCI, Bethesda, MD 20892 USA. [Staudt, Louis M.] NCI, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. [Repici, Jacqueline] Celgene Corp, Basking Ridge, NJ USA. [Song, Dale] Celgene Corp, Summit, NJ USA. [Manzke, Oliver] Celgene Corp, Boudry, Switzerland. [Lewis, Ian D.] Royal Adelaide Hosp, Adelaide, SA 5000, Australia. RI Linton, Kim/O-9903-2015; Zinzani, Pier Luigi/J-9182-2016 OI Linton, Kim/0000-0002-3294-1548; Zinzani, Pier Luigi/0000-0002-2112-2651 NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 2021 L ST NW, SUITE 900, WASHINGTON, DC 20036 USA SN 0006-4971 EI 1528-0020 J9 BLOOD JI Blood PD DEC 6 PY 2014 VL 124 IS 21 PG 4 WC Hematology SC Hematology GA CA9KX UT WOS:000349243506190 ER PT J AU Davidson-Moncada, J Sato, N Hoyt, RF Reger, RN Thomas, M Clevenger, R Metzger, ME Donahue, RE Eclarinal, PC Szajek, L Griffiths, GL Dunbar, CE Choyke, P Childs, R AF Davidson-Moncada, Jan Sato, Noriko Hoyt, Robert F. Reger, Robert N. Thomas, Marvin Clevenger, Randy Metzger, Mark E. Donahue, Robert E. Eclarinal, Philip C. Szajek, Lawrence Griffiths, Gary L. Dunbar, Cynthia E. Choyke, Peter Childs, Richard TI A Novel Method to Study the in Vivo Trafficking and Homing of Adoptively Transferred NK Cells in Rhesus Macaques and Humans SO BLOOD LA English DT Meeting Abstract CT 56th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2014 CL San Francisco, CA SP Amer Soc Hematol C1 [Davidson-Moncada, Jan; Reger, Robert N.; Thomas, Marvin; Clevenger, Randy; Eclarinal, Philip C.; Szajek, Lawrence; Dunbar, Cynthia E.] NIH, Bethesda, MD 20892 USA. [Sato, Noriko; Hoyt, Robert F.; Choyke, Peter] NCI, NIH, Bethesda, MD 20892 USA. [Metzger, Mark E.; Donahue, Robert E.; Childs, Richard] NHLBI, NIH, Bethesda, MD 20892 USA. [Griffiths, Gary L.] Frederick Natl Lab Canc Res, Frederick, MD USA. NR 0 TC 0 Z9 0 U1 1 U2 3 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 2021 L ST NW, SUITE 900, WASHINGTON, DC 20036 USA SN 0006-4971 EI 1528-0020 J9 BLOOD JI Blood PD DEC 6 PY 2014 VL 124 IS 21 PG 3 WC Hematology SC Hematology GA CA9HU UT WOS:000349233807146 ER PT J AU Donahue, RE Metzger, ME Bonifacino, AC Parker, DM Leitman, SF Cullis, H Lienesch, M AF Donahue, Robert E. Metzger, Mark E. Bonifacino, Aylin C. Parker, Drew M. Leitman, Susan F. Cullis, Herb Lienesch, Maura TI Optimization of the Spectra Optia for Leukapheresis of Very Small Subjects SO BLOOD LA English DT Meeting Abstract CT 56th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2014 CL San Francisco, CA SP Amer Soc Hematol C1 [Donahue, Robert E.; Metzger, Mark E.; Bonifacino, Aylin C.] NHLBI, NIH, Bethesda, MD 20892 USA. [Parker, Drew M.; Lienesch, Maura] Terumo BCT Inc, Lakewood, CO USA. [Leitman, Susan F.] NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 2021 L ST NW, SUITE 900, WASHINGTON, DC 20036 USA SN 0006-4971 EI 1528-0020 J9 BLOOD JI Blood PD DEC 6 PY 2014 VL 124 IS 21 PG 3 WC Hematology SC Hematology GA CA9HU UT WOS:000349233802091 ER PT J AU Donahue, RE Srinivasula, S Uchida, N Kim, I Duralde, G DeGrange, P Claire, MS Reba, RC Bonifacino, AC Krouse, AE Metzger, ME Paik, CH Lane, HC Tisdale, JF Di Mascio, M AF Donahue, Robert E. Srinivasula, Sharat Uchida, Naoya Kim, Insook Duralde, Gorka DeGrange, Paula Claire, Marisa St. Reba, Richard C. Bonifacino, Aylin C. Krouse, Allen E. Metzger, Mark E. Paik, Chang H. Lane, H. Clifford Tisdale, John F. Di Mascio, Michele TI Evaluation of CD4+Cell Recovery in Vivo Using Single Photon Emission Tomography (SPECT) in Real Time Following CD34+Cell Transplantation in Rhesus Macaques SO BLOOD LA English DT Meeting Abstract CT 56th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2014 CL San Francisco, CA SP Amer Soc Hematol C1 [Donahue, Robert E.; Uchida, Naoya; Bonifacino, Aylin C.; Krouse, Allen E.; Metzger, Mark E.] NHLBI, NIH, Bethesda, MD 20892 USA. [Srinivasula, Sharat] Leidos Biomed Res Inc, FNLCR, Frederick, MD USA. [Kim, Insook] Frederick Natl Lab, Frederick, MD USA. [Duralde, Gorka; DeGrange, Paula; Claire, Marisa St.; Lane, H. Clifford; Di Mascio, Michele] NIAID, NIH, Bethesda, MD 20892 USA. [Reba, Richard C.; Paik, Chang H.] NIH, Ctr Clin, Bethesda, MD 20892 USA. [Tisdale, John F.] NIDDK, NHLBI, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 2021 L ST NW, SUITE 900, WASHINGTON, DC 20036 USA SN 0006-4971 EI 1528-0020 J9 BLOOD JI Blood PD DEC 6 PY 2014 VL 124 IS 21 PG 4 WC Hematology SC Hematology GA CA9HU UT WOS:000349233802021 ER PT J AU Dumitriu, B Townsley, DM Chen, C Calado, RT Scheinberg, P Young, NS AF Dumitriu, Bogdan Townsley, Danielle M. Chen, Christina Calado, Rodrigo T. Scheinberg, Phillip Young, Neal S. TI Telomere Elongation and Hematologic Improvement in Humans Treated with Androgens: A Prospective Clinical Trial of Danazol in Telomeropathies SO BLOOD LA English DT Meeting Abstract CT 56th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2014 CL San Francisco, CA SP Amer Soc Hematol C1 [Dumitriu, Bogdan] NHLBI, NIH, Bethesda, MD 20892 USA. [Townsley, Danielle M.] NHLBI, Hematol Branch, NIH, Bethesda, MD 20892 USA. [Chen, Christina; Young, Neal S.] NIH, Bethesda, MD 20892 USA. [Calado, Rodrigo T.] Univ Sao Paulo, Sch Med, BR-14049 Ribeirao Preto, Brazil. [Scheinberg, Phillip] Hosp Sao Jose, Sao Paulo, Brazil. RI Calado, Rodrigo/G-2619-2011 NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 2021 L ST NW, SUITE 900, WASHINGTON, DC 20036 USA SN 0006-4971 EI 1528-0020 J9 BLOOD JI Blood PD DEC 6 PY 2014 VL 124 IS 21 PG 3 WC Hematology SC Hematology GA CA9HU UT WOS:000349233802169 ER PT J AU Durham, B Ma, J Kim, E Choi, JK Campbell, P Estrada-Veras, J Walsh, MP Lacouture, ME Chung, YR Nakitandwe, J Diamond, E Hyman, DM Rampal, RK Patel, M Park, CY Gruber, TA Abdel-Wahab, O AF Durham, Benjamin Ma, Jing Kim, Eunhee Choi, John K. Campbell, Patrick Estrada-Veras, Juvianee Walsh, Michael P. Lacouture, Mario E. Chung, Young Rock Nakitandwe, Joy Diamond, Eli Hyman, David M. Rampal, Raajit K. Patel, Minal Park, Christopher Y. Gruber, Tanja A. Abdel-Wahab, Omar TI Unraveling the Molecular Basis of Langerhans and Non-Langerhans Cell Histiocytic Neoplasms through Whole Exome Sequencing SO BLOOD LA English DT Meeting Abstract CT 56th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2014 CL San Francisco, CA SP Amer Soc Hematol C1 [Durham, Benjamin; Kim, Eunhee; Lacouture, Mario E.; Chung, Young Rock; Diamond, Eli; Hyman, David M.; Rampal, Raajit K.; Patel, Minal; Park, Christopher Y.; Abdel-Wahab, Omar] Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. [Ma, Jing; Choi, John K.; Campbell, Patrick; Walsh, Michael P.; Nakitandwe, Joy; Gruber, Tanja A.] St Jude Childrens Res Hosp, Memphis, TN 38105 USA. [Estrada-Veras, Juvianee] NHGRI, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 2021 L ST NW, SUITE 900, WASHINGTON, DC 20036 USA SN 0006-4971 EI 1528-0020 J9 BLOOD JI Blood PD DEC 6 PY 2014 VL 124 IS 21 PG 3 WC Hematology SC Hematology GA CA9HU UT WOS:000349233801061 ER PT J AU Fitzhugh, C Hannoush, H Sachdev, V Di Maggio, R Coles, W Link, M Katradis, E Zhao, XC Tisdale, JF Hsieh, M AF Fitzhugh, Courtney Hannoush, Hwaida Sachdev, Vandana Di Maggio, Rosario Coles, Wynona Link, Mary Katradis, Evan Zhao, Xiongce Tisdale, John F. Hsieh, Matthew TI Nonmyeloablative Hematopoietic Stem Cell Transplantation Improves a Marker of Diastolic Dysfunction in Patients with Sickle Cell Disease SO BLOOD LA English DT Meeting Abstract CT 56th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2014 CL San Francisco, CA SP Amer Soc Hematol C1 [Fitzhugh, Courtney; Hannoush, Hwaida; Sachdev, Vandana] NHLBI, NIH, Bethesda, MD 20892 USA. [Di Maggio, Rosario; Coles, Wynona; Link, Mary; Katradis, Evan; Tisdale, John F.; Hsieh, Matthew] NHLBI, NIDDK, NIH, Bethesda, MD 20892 USA. [Zhao, Xiongce] NIDDK, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 2021 L ST NW, SUITE 900, WASHINGTON, DC 20036 USA SN 0006-4971 EI 1528-0020 J9 BLOOD JI Blood PD DEC 6 PY 2014 VL 124 IS 21 PG 3 WC Hematology SC Hematology GA CA9HU UT WOS:000349233801174 ER PT J AU Florea, AED Braylan, RC Schafernak, KT Pittaluga, S Holland, SM Uzel, G Calvo, KR AF Florea, Alina E. Dulau Braylan, Raul C. Schafernak, Kristian T. Pittaluga, Stefania Holland, Steven M. Uzel, Gulbu Calvo, Katherine R. TI Abnormal B-Cell Maturation Pattern in the Bone Marrow of Patients with Germline Mutations in PIK3CD SO BLOOD LA English DT Meeting Abstract CT 56th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2014 CL San Francisco, CA SP Amer Soc Hematol C1 [Florea, Alina E. Dulau; Braylan, Raul C.; Pittaluga, Stefania; Holland, Steven M.; Uzel, Gulbu; Calvo, Katherine R.] NIH, Bethesda, MD 20892 USA. [Schafernak, Kristian T.] Lurie Childrens Hosp, Chicago, IL USA. NR 0 TC 0 Z9 0 U1 4 U2 4 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 2021 L ST NW, SUITE 900, WASHINGTON, DC 20036 USA SN 0006-4971 EI 1528-0020 J9 BLOOD JI Blood PD DEC 6 PY 2014 VL 124 IS 21 PG 3 WC Hematology SC Hematology GA CA9HU UT WOS:000349233803070 ER PT J AU Gine, E Bea, S Navarro, A Martinez-Cibrian, N Salaverria, I Martin-Garcia, D Jares, P Pinyol, M Royo, C Clot, G Aymerich, M Villamor, N Colomo, L Martinez, A Valera, A Rozman, M Enjuanes, A Forcada, P Muntanola, A Hartmann, E Rosenwald, A Ott, G Gonzalez, M Hernandez-Rivas, JM Klapper, W Siebert, R Wiestner, A Wilson, WH Calasanz, MJ Magnano, L Rovira, J Colomer, D Campo, E Lopez-Guillermo, A AF Gine, Eva Bea, Slvia Navarro, Alba Martinez-Cibrian, Nuria Salaverria, Itziar Martin-Garcia, David Jares, Pedro Pinyol, Magda Royo, Cristina Clot, Guillem Aymerich, Marta Villamor, Neus Colomo, Lluis Martinez, Antonio Valera, Alexandra Rozman, Maria Enjuanes, Anna Forcada, Pilar Muntanola, Anna Hartmann, Elena Rosenwald, Andreas Ott, German Gonzalez, Marcos Hernandez-Rivas, Jesus M. Klapper, Wolfram Siebert, Reiner Wiestner, Adrian Wilson, Wyndham H. Jose Calasanz, Maria Magnano, Laura Rovira, Jordina Colomer, Dolors Campo, Elias Lopez-Guillermo, Armando TI Risk of Central Nervous System (CNS) Involvement in Patients with Mantle Cell Lymphoma (MCL): Analysis of Clinico-Biological Factors in a Series of 283 Cases SO BLOOD LA English DT Meeting Abstract CT 56th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2014 CL San Francisco, CA SP Amer Soc Hematol C1 [Gine, Eva; Bea, Slvia; Navarro, Alba; Martinez-Cibrian, Nuria; Salaverria, Itziar; Martin-Garcia, David; Jares, Pedro; Pinyol, Magda; Royo, Cristina; Clot, Guillem; Aymerich, Marta; Villamor, Neus; Colomo, Lluis; Martinez, Antonio; Valera, Alexandra; Rozman, Maria; Enjuanes, Anna; Magnano, Laura; Rovira, Jordina; Colomer, Dolors; Campo, Elias; Lopez-Guillermo, Armando] Hosp Clin Barcelona, IDIBAPS, Barcelona, Spain. [Forcada, Pilar; Muntanola, Anna] Hosp Mutua Terrassa, Terrassa, Spain. [Hartmann, Elena; Rosenwald, Andreas] Univ Wurzburg, D-97070 Wurzburg, Germany. [Ott, German] Robert Bosch Krankenhaus, Stuttgart, Germany. [Ott, German] Dr Margarete Fischer Bosch Inst Clin Pharmacol, Stuttgart, Germany. [Gonzalez, Marcos] Hosp Clin U, Dept Hematol, Salamanca, Spain. [Hernandez-Rivas, Jesus M.] Hosp Clin Salamanca, IBSAL, Salamanca, Spain. [Klapper, Wolfram; Siebert, Reiner] Univ Kiel, Kiel, Germany. [Wiestner, Adrian] NHLBI, NIH, Bethesda, MD 20892 USA. [Wilson, Wyndham H.] NCI, Bethesda, MD 20892 USA. [Jose Calasanz, Maria] Univ Navarra, E-31080 Pamplona, Spain. RI Navarro, Alba/H-2611-2015; Royo, Cristina/H-3193-2015; ENJUANES, Anna/H-3245-2015; Calasanz, MJ/R-5813-2016; Colomo, Luis/A-2259-2016 OI Navarro, Alba/0000-0002-4041-0974; Royo, Cristina/0000-0002-1214-4656; ENJUANES, Anna/0000-0002-4679-6687; Calasanz, MJ/0000-0002-0374-3008; Colomo, Luis/0000-0001-5236-5085 NR 0 TC 0 Z9 0 U1 1 U2 2 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 2021 L ST NW, SUITE 900, WASHINGTON, DC 20036 USA SN 0006-4971 EI 1528-0020 J9 BLOOD JI Blood PD DEC 6 PY 2014 VL 124 IS 21 PG 3 WC Hematology SC Hematology GA CA9HU UT WOS:000349233802220 ER PT J AU Gondek, LP Lim, Y Makishima, H Wang, QJ Maciejewski, JP Aplan, PD DeZern, AE Matsui, W AF Gondek, Lukasz P. Lim, Yiting Makishima, Hideki Wang, Qiuju Maciejewski, Jaroslaw P. Aplan, Peter D. DeZern, Amy E. Matsui, William TI Aberrant Hedgehog Pathway Activity Marks Clinical MDS Progression and Accelerates Leukemic Transformation in Vivo SO BLOOD LA English DT Meeting Abstract CT 56th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2014 CL San Francisco, CA SP Amer Soc Hematol C1 [Gondek, Lukasz P.; Lim, Yiting; Wang, Qiuju; DeZern, Amy E.; Matsui, William] Johns Hopkins Univ, Baltimore, MD USA. [Makishima, Hideki; Maciejewski, Jaroslaw P.] Cleveland Clin, Cleveland, OH 44106 USA. [Aplan, Peter D.] NCI, NIH, Bethesda, MD 20892 USA. RI Aplan, Peter/K-9064-2016 NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 2021 L ST NW, SUITE 900, WASHINGTON, DC 20036 USA SN 0006-4971 EI 1528-0020 J9 BLOOD JI Blood PD DEC 6 PY 2014 VL 124 IS 21 PG 3 WC Hematology SC Hematology GA CA9HU UT WOS:000349233800188 ER PT J AU Gough, SM Goldberg, L Pineda, M Walker, RL Zhu, YLJ Bilke, S Meltzer, PS Aplan, PD AF Gough, Sheryl M. Goldberg, Liat Pineda, Marbin Walker, Robert L. Zhu, Yuelin J. Bilke, Sven Meltzer, Paul S. Aplan, Peter D. TI Spontaneous Mutations of Bcor and Jak1/2 genes Lead to an Aggressive Leukemia of B-1 Progenitor B Cells SO BLOOD LA English DT Meeting Abstract CT 56th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2014 CL San Francisco, CA SP Amer Soc Hematol C1 [Gough, Sheryl M.; Goldberg, Liat; Pineda, Marbin; Walker, Robert L.; Zhu, Yuelin J.; Bilke, Sven; Meltzer, Paul S.; Aplan, Peter D.] NCI, NIH, CCR, Bethesda, MD 20892 USA. RI Aplan, Peter/K-9064-2016 NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 2021 L ST NW, SUITE 900, WASHINGTON, DC 20036 USA SN 0006-4971 EI 1528-0020 J9 BLOOD JI Blood PD DEC 6 PY 2014 VL 124 IS 21 PG 3 WC Hematology SC Hematology GA CA9HU UT WOS:000349233800223 ER PT J AU Griffiths, EA Carter-Cooper, B Tolu, S Ford, LA Lapidus, RG Wetzler, M Wang, ES Etemadi, A Emadi, A AF Griffiths, Elizabeth A. Carter-Cooper, Brandon Tolu, Seda Ford, Laurie A. Lapidus, Rena G. Wetzler, Meir Wang, Eunice S. Etemadi, Arash Emadi, Ashkan TI Presence of Isocitrate Dehydrogenase (IDH) Mutations May Predict Clinical Response to Hypomethylating Agents in Patients with Acute Myeloid Leukemia (AML) SO BLOOD LA English DT Meeting Abstract CT 56th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2014 CL San Francisco, CA SP Amer Soc Hematol C1 [Griffiths, Elizabeth A.; Ford, Laurie A.; Wetzler, Meir; Wang, Eunice S.] Roswell Pk Canc Inst, Buffalo, NY 14263 USA. [Carter-Cooper, Brandon; Tolu, Seda; Lapidus, Rena G.; Emadi, Ashkan] Univ Maryland, Greenebaum Canc Ctr, Baltimore, MD 21201 USA. [Etemadi, Arash] NCI, Div Canc Epidemiol & Genet, NIH, Bethesda, MD 20892 USA. RI Etemadi, Arash/C-1386-2016 OI Etemadi, Arash/0000-0002-3458-1072 NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 2021 L ST NW, SUITE 900, WASHINGTON, DC 20036 USA SN 0006-4971 EI 1528-0020 J9 BLOOD JI Blood PD DEC 6 PY 2014 VL 124 IS 21 PG 3 WC Hematology SC Hematology GA CA9KX UT WOS:000349243501091 ER PT J AU Herman, SEM Mustafa, RZ Farooqui, M Wiestner, A AF Herman, Sarah E. M. Mustafa, Rashida Z. Farooqui, Mohammed Wiestner, Adrian TI In Vivo Ibrutinib Abrogates BCR-Dependent Adhesion in Tumor Cells of Patients with Chronic Lymphocytic Leukemia SO BLOOD LA English DT Meeting Abstract CT 56th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2014 CL San Francisco, CA SP Amer Soc Hematol C1 [Herman, Sarah E. M.; Mustafa, Rashida Z.; Farooqui, Mohammed; Wiestner, Adrian] NIH, Bethesda, MD 20892 USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 2021 L ST NW, SUITE 900, WASHINGTON, DC 20036 USA SN 0006-4971 EI 1528-0020 J9 BLOOD JI Blood PD DEC 6 PY 2014 VL 124 IS 21 PG 3 WC Hematology SC Hematology GA CA9KX UT WOS:000349243500175 ER PT J AU Hosokawa, K Muranski, P Feng, XM Keyvanfar, K Townsley, DM Dumitriu, B Chen, JC Kajigaya, S Taylor, JG Hourigan, CS Barrett, J Young, NS AF Hosokawa, Kohei Muranski, Pawel Feng, Xingmin Keyvanfar, Keyvan Townsley, Danielle M. Dumitriu, Bogdan Chen, Jichun Kajigaya, Sachiko Taylor, James G. Hourigan, Christopher S. Barrett, John Young, Neal S. TI Altered microRNAs in T Cells from Patients with Acquired Aplastic Anemia SO BLOOD LA English DT Meeting Abstract CT 56th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2014 CL San Francisco, CA SP Amer Soc Hematol C1 [Hosokawa, Kohei; Muranski, Pawel; Feng, Xingmin; Keyvanfar, Keyvan; Townsley, Danielle M.; Chen, Jichun; Kajigaya, Sachiko; Taylor, James G.; Hourigan, Christopher S.; Barrett, John] NHLBI, Hematol Branch, NIH, Bethesda, MD 20892 USA. [Dumitriu, Bogdan; Young, Neal S.] NHLBI, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 2021 L ST NW, SUITE 900, WASHINGTON, DC 20036 USA SN 0006-4971 EI 1528-0020 J9 BLOOD JI Blood PD DEC 6 PY 2014 VL 124 IS 21 PG 3 WC Hematology SC Hematology GA CA9HU UT WOS:000349233807018 ER PT J AU Hsiung, CCS Morrissey, C Udugama, M Frank, C Keller, CA Baek, S Giardine, B Crawford, GE Sung, MH Raj, A Hardison, RC Blobel, GA AF Hsiung, Chris C. S. Morrissey, Christapher Udugama, Maheshi Frank, Christopher Keller, Cheryl A. Baek, Songjoon Giardine, Belinda Crawford, Gregory E. Sung, Myong-Hee Raj, Arjun Hardison, Ross C. Blobel, Gerd A. TI Epigenetics of Cellular Memory: Insights from the Chromatin Accessibility Landscape of the Mitotic Genome SO BLOOD LA English DT Meeting Abstract CT 56th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2014 CL San Francisco, CA SP Amer Soc Hematol C1 [Hsiung, Chris C. S.; Udugama, Maheshi; Blobel, Gerd A.] Childrens Hosp Philadelphia, Philadelphia, PA 19104 USA. [Hsiung, Chris C. S.] Univ Penn, Perelman Sch Med, Philadelphia, PA 19104 USA. [Morrissey, Christapher; Keller, Cheryl A.; Giardine, Belinda; Hardison, Ross C.] Penn State Univ, University Pk, PA 16802 USA. [Frank, Christopher; Crawford, Gregory E.] Duke Univ, Durham, NC USA. [Baek, Songjoon; Sung, Myong-Hee] NIH, Bethesda, MD 20892 USA. [Raj, Arjun] Univ Penn, Philadelphia, PA 19104 USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 2021 L ST NW, SUITE 900, WASHINGTON, DC 20036 USA SN 0006-4971 EI 1528-0020 J9 BLOOD JI Blood PD DEC 6 PY 2014 VL 124 IS 21 PG 3 WC Hematology SC Hematology GA CA9HU UT WOS:000349233807040 ER PT J AU Jacoby, E Qin, HY Yang, YM Chien, CD Fry, TJ AF Jacoby, Elad Qin, Haiying Yang, Yinmeng Chien, Christopher Daniel Fry, Terry J. TI CD19 CAR T Cells Maintain Efficacy in the Allogeneic Environment but Mediate Acute Graft-Versus-HostDisease Only in the Presence CD19+Acute Lymphoblastic Leukemia SO BLOOD LA English DT Meeting Abstract CT 56th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2014 CL San Francisco, CA SP Amer Soc Hematol C1 [Jacoby, Elad; Qin, Haiying; Yang, Yinmeng; Chien, Christopher Daniel; Fry, Terry J.] NCI, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 2021 L ST NW, SUITE 900, WASHINGTON, DC 20036 USA SN 0006-4971 EI 1528-0020 J9 BLOOD JI Blood PD DEC 6 PY 2014 VL 124 IS 21 PG 3 WC Hematology SC Hematology GA CA9KX UT WOS:000349243505107 ER PT J AU Jiang, L Zhou, JX Morse, H Xu, YL AF Jiang, Lei Zhou, Jeff Xiwu Morse, Herbert Xu, Yulian TI The Stimulatory Role of CD300a in Diffuse Large B-Cell Lymphoma SO BLOOD LA English DT Meeting Abstract CT 56th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2014 CL San Francisco, CA SP Amer Soc Hematol C1 [Jiang, Lei; Xu, Yulian] Ningbo Univ, Ningbo 315211, Zhejiang, Peoples R China. [Zhou, Jeff Xiwu] Ningbo Univ, Sch Med, Ningbo 315211, Zhejiang, Peoples R China. [Morse, Herbert] NIAID, NIH, Rockville, MD USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 2021 L ST NW, SUITE 900, WASHINGTON, DC 20036 USA SN 0006-4971 EI 1528-0020 J9 BLOOD JI Blood PD DEC 6 PY 2014 VL 124 IS 21 PG 2 WC Hematology SC Hematology GA CA9HU UT WOS:000349233806203 ER PT J AU Jun, HS Chou, JY AF Jun, Hyun Sik Chou, Janice Y. TI Mesenchymal Stem Cells Lacking Glucose-6-Phosphatase-beta Exhibit Disturbed Energy Homeostasis and Defective Adipogenesis SO BLOOD LA English DT Meeting Abstract CT 56th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2014 CL San Francisco, CA SP Amer Soc Hematol C1 [Jun, Hyun Sik; Chou, Janice Y.] NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 1 U2 3 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 2021 L ST NW, SUITE 900, WASHINGTON, DC 20036 USA SN 0006-4971 EI 1528-0020 J9 BLOOD JI Blood PD DEC 6 PY 2014 VL 124 IS 21 PG 3 WC Hematology SC Hematology GA CA9KX UT WOS:000349243507128 ER PT J AU Jung, M Davidson-Moncada, JK Wu, CF Koelle, S Winkler, T Townsley, DM Hsu, A Keyvanfar, K Holland, SM Hickstein, DD Childs, RW Dunbar, CE AF Jung, Moonjung Davidson-Moncada, Jan K. Wu, Chuanfeng Koelle, Samson Winkler, Thomas Townsley, Danielle M. Hsu, Amy Keyvanfar, Keyvan Holland, Steven M. Hickstein, Dennis D. Childs, Richard W. Dunbar, Cynthia E. TI Specific Impaired CD56+NK Cell Development in GATA2 Deficiency As Revealed By Ex Vivo NK Expansion SO BLOOD LA English DT Meeting Abstract CT 56th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2014 CL San Francisco, CA SP Amer Soc Hematol C1 [Jung, Moonjung; Davidson-Moncada, Jan K.; Wu, Chuanfeng; Koelle, Samson; Winkler, Thomas; Hsu, Amy; Keyvanfar, Keyvan; Holland, Steven M.; Hickstein, Dennis D.; Childs, Richard W.; Dunbar, Cynthia E.] NIH, Bethesda, MD 20892 USA. [Townsley, Danielle M.] NHLBI, Hematol Branch, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 2021 L ST NW, SUITE 900, WASHINGTON, DC 20036 USA SN 0006-4971 EI 1528-0020 J9 BLOOD JI Blood PD DEC 6 PY 2014 VL 124 IS 21 PG 3 WC Hematology SC Hematology GA CA9HU UT WOS:000349233802180 ER PT J AU Kapadia, E Jacoby, E Kohler, M Haso, W Chien, CD Fry, TJ AF Kapadia, Ekta Jacoby, Elad Kohler, Mark Haso, Waleed Chien, Christopher Daniel Fry, Terry J. TI 41BBL-Based Activation and Expansion of Autologous Natural Killer Cells Results in Enhanced Activity Against Leukemia Including ALL SO BLOOD LA English DT Meeting Abstract CT 56th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2014 CL San Francisco, CA SP Amer Soc Hematol C1 [Kapadia, Ekta] Childrens Natl Med Ctr, Washington, DC 20010 USA. [Kapadia, Ekta] NCI, Rockville, MD USA. [Jacoby, Elad; Haso, Waleed; Chien, Christopher Daniel; Fry, Terry J.] NCI, NIH, Bethesda, MD 20892 USA. [Kohler, Mark] NIH, Rockville, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 2021 L ST NW, SUITE 900, WASHINGTON, DC 20036 USA SN 0006-4971 EI 1528-0020 J9 BLOOD JI Blood PD DEC 6 PY 2014 VL 124 IS 21 PG 3 WC Hematology SC Hematology GA CA9HU UT WOS:000349233800136 ER PT J AU Kendrick, SL Tus, K Scott, DW Wright, G Jaffe, ES Rosenwald, A Campo, E Chan, WC Connors, JM Braziel, RM Ott, G Delabie, J Cook, JR Weisenburger, DD Greiner, TC Fu, K Staudt, LM Gascoyne, RD Rimsza, LM AF Kendrick, Samantha L. Tus, Katalin Scott, David W. Wright, George Jaffe, Elaine S. Rosenwald, Andreas Campo, Elias Chan, Wing Chung Connors, Joseph M. Braziel, Rita M. Ott, German Delabie, Jan Cook, James R. Weisenburger, Dennis D. Greiner, Timothy C. Fu, Kai Staudt, Louis M. Gascoyne, Randy D. Rimsza, Lisa M. TI Cell-of-Origin Subtype Classification of Diffuse Large B-Cell Lymphoma Using the Lymph2Cx Assay Retains Relevance in the Context of BCL2 and MYC Expression Status SO BLOOD LA English DT Meeting Abstract CT 56th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2014 CL San Francisco, CA SP Amer Soc Hematol C1 [Kendrick, Samantha L.; Tus, Katalin] Univ Arizona, Tucson, AZ USA. [Scott, David W.; Connors, Joseph M.] British Columbia Canc Agcy, Vancouver, BC V5Z 4E6, Canada. [Wright, George; Jaffe, Elaine S.] NCI, Bethesda, MD 20892 USA. [Rosenwald, Andreas] Univ Wurzburg, D-97070 Wurzburg, Germany. [Campo, Elias] Hosp Clin Barcelona, Barcelona, Spain. [Chan, Wing Chung; Greiner, Timothy C.; Fu, Kai] Univ Nebraska Med Ctr, Omaha, NE USA. [Braziel, Rita M.] Oregon Hlth & Sci Univ, Portland, OR 97201 USA. [Ott, German] Robert Bosch Krankenhaus, Stuttgart, Germany. [Ott, German] Dr Margarete Fischer Bosch Inst Clin Pharmacol, Stuttgart, Germany. [Delabie, Jan] Norwegian Radium Hosp, Oslo Univ Hosp, Oslo, Norway. [Cook, James R.] Cleveland Clin, Cleveland, OH 44106 USA. [Weisenburger, Dennis D.] City Hope Natl Med Ctr, Duarte, CA 91010 USA. [Staudt, Louis M.] NCI, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. [Gascoyne, Randy D.] Ctr Lymphoid Canc, Vancouver, BC, Canada. [Rimsza, Lisa M.] Univ Arizona, Dept Pathol, Tucson, AZ USA. RI Jaffe, Elaine/G-8984-2014 OI Jaffe, Elaine/0000-0003-4632-0301 NR 0 TC 0 Z9 0 U1 1 U2 2 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 2021 L ST NW, SUITE 900, WASHINGTON, DC 20036 USA SN 0006-4971 EI 1528-0020 J9 BLOOD JI Blood PD DEC 6 PY 2014 VL 124 IS 21 PG 4 WC Hematology SC Hematology GA CA9KX UT WOS:000349243502221 ER PT J AU Kim, YC Zhang, AH Pratt, KP Shevach, E Scott, DW AF Kim, Yong Chan Zhang, Aihong Pratt, Kathleen P. Shevach, Ethan Scott, David William TI Engineered Antigen-Specific Human Regulatory T Cells Suppress Both FVIII-Specific T- and B-Cell Responses SO BLOOD LA English DT Meeting Abstract CT 56th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2014 CL San Francisco, CA SP Amer Soc Hematol C1 [Kim, Yong Chan; Zhang, Aihong; Pratt, Kathleen P.; Scott, David William] Uniformed Serv Univ Hlth Sci, Dept Med, Bethesda, MD 20814 USA. [Shevach, Ethan] NIH, Bethesda, ME USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 2021 L ST NW, SUITE 900, WASHINGTON, DC 20036 USA SN 0006-4971 EI 1528-0020 J9 BLOOD JI Blood PD DEC 6 PY 2014 VL 124 IS 21 PG 3 WC Hematology SC Hematology GA CA9HU UT WOS:000349233807093 ER PT J AU Kirimunda, S Kinyera, T Ogwang, M Reynolds, SJ Joloba, M Pfeiffer, RM Goedert, JJ Bhatia, K Mbulaiteye, SM AF Kirimunda, Samuel Kinyera, Tobias Ogwang, Martin Reynolds, Steven J. Joloba, Moses Pfeiffer, Ruth M. Goedert, James J. Bhatia, Kishor Mbulaiteye, Sam M. TI Risk for Endemic Burkitt Lymphoma Is Elevated in Children Who Are Resistant to Blood-Stage Plasmodium Falciparum Malaria Infection: Preliminary Results from the Emblem Study SO BLOOD LA English DT Meeting Abstract CT 56th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2014 CL San Francisco, CA SP Amer Soc Hematol C1 [Kirimunda, Samuel; Joloba, Moses] Makerere Coll Hlth Sci, Kampala, Uganda. [Kinyera, Tobias] EMBLEM Study, Gulu, Uganda. [Ogwang, Martin] St Mary Hosp, Lacor, Gulu, Uganda. [Reynolds, Steven J.] NIH, Div Intramural Res, Bethesda, MD 20892 USA. [Pfeiffer, Ruth M.] NCI, Div Canc Epidemiol & Genet, NIH, Bethesda, MD 20892 USA. [Goedert, James J.] NCI, NIH, Rockville, MD USA. [Bhatia, Kishor; Mbulaiteye, Sam M.] NCI, Div Canc Epidemiol & Genet, NIH, Rockville, MD USA. NR 0 TC 0 Z9 0 U1 1 U2 2 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 2021 L ST NW, SUITE 900, WASHINGTON, DC 20036 USA SN 0006-4971 EI 1528-0020 J9 BLOOD JI Blood PD DEC 6 PY 2014 VL 124 IS 21 PG 3 WC Hematology SC Hematology GA CA9KX UT WOS:000349243505150 ER PT J AU Koelle, S Wu, CF Li, B Lu, R Donahue, RE Dunbar, CE AF Koelle, Samson Wu, Chuanfeng Li, Brian Lu, Rong Donahue, Robert E. Dunbar, Cynthia E. TI Long-Term Hematopoietic Clonal Stability Tracked Using Molecular Barcoding in Non-Human Primates SO BLOOD LA English DT Meeting Abstract CT 56th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2014 CL San Francisco, CA SP Amer Soc Hematol C1 [Koelle, Samson; Wu, Chuanfeng; Dunbar, Cynthia E.] NIH, Bethesda, MD 20892 USA. [Li, Brian] Boston Childrens Hosp, Boston, MA USA. [Lu, Rong] Univ So Calif, Los Angeles, CA USA. [Donahue, Robert E.] NHLBI, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 2021 L ST NW, SUITE 900, WASHINGTON, DC 20036 USA SN 0006-4971 EI 1528-0020 J9 BLOOD JI Blood PD DEC 6 PY 2014 VL 124 IS 21 PG 3 WC Hematology SC Hematology GA CA9HU UT WOS:000349233804221 ER PT J AU Kordasti, S Seidl, T Ellis, RJ Kulasekararaj, A Feng, XM Townsley, DM Heck, S Young, NS Marsh, JC Mufti, GJ AF Kordasti, Shahram Seidl, Thomas Ellis, Richard J. Kulasekararaj, Austin Feng, Xingmin Townsley, Danielle M. Heck, Susanne Young, Neal S. Marsh, Judith C. Mufti, Ghulam J. TI High Resolution Mass Cytometry (CyTOF) in Aplastic Anaemia (AA) Can Identify an Aberrant Treg Subset with Pro-Inflammatory Properties, Predicting Poor Response to Immunosuppressive Therapy SO BLOOD LA English DT Meeting Abstract CT 56th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2014 CL San Francisco, CA SP Amer Soc Hematol C1 [Kordasti, Shahram; Mufti, Ghulam J.] Kings Coll Hosp London, London, England. [Kordasti, Shahram; Seidl, Thomas; Ellis, Richard J.; Heck, Susanne; Marsh, Judith C.; Mufti, Ghulam J.] Kings Coll London, London WC2R 2LS, England. [Ellis, Richard J.; Heck, Susanne] Guys & St Thomas NHS Fdn Trust, London, England. [Kulasekararaj, Austin] Dept Haematol Med, London, England. [Kulasekararaj, Austin; Marsh, Judith C.] NHS Fdn Trust, Kings Coll Hosp London, London, England. [Feng, Xingmin; Townsley, Danielle M.] NIH, Bethesda, MD 20892 USA. [Young, Neal S.] NHLBI, NIH, Bethesda, MD 20892 USA. NR 0 TC 1 Z9 1 U1 1 U2 2 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 2021 L ST NW, SUITE 900, WASHINGTON, DC 20036 USA SN 0006-4971 EI 1528-0020 J9 BLOOD JI Blood PD DEC 6 PY 2014 VL 124 IS 21 PG 4 WC Hematology SC Hematology GA CA9KX UT WOS:000349243504198 ER PT J AU Korde, N Mailankody, S Roschewski, M Faham, M Kotwaliwale, C Moorhead, M Kwok, ML Manasanch, EE Bhutani, M Tageja, N Kazandjian, D Costello, R Zhang, Y Zingone, A Burton, D Mulquin, M Carpenter, A Zuchlinski, D Lamping, E Carter, G Morrison, C Kurdziel, K Lindenberg, M Kurlander, R Maric, I Calvo, KR Braylan, RC Yuan, C Stetler-Stevenson, M Arthur, DC Steinberg, SM Figg, WD Choyke, P Landgren, O AF Korde, Neha Mailankody, Sham Roschewski, Mark Faham, Malek Kotwaliwale, Chitra Moorhead, Martin Kwok, Mary L. Manasanch, Elisabet E. Bhutani, Manisha Tageja, Nishant Kazandjian, Dickran Costello, Rene Zhang, Yong Zingone, Adriana Burton, Debbie Mulquin, Marcia Carpenter, Ashley Zuchlinski, Diamond Lamping, Elizabeth Carter, George Morrison, Candis Kurdziel, Karen Lindenberg, Maria Kurlander, Roger Maric, Irina Calvo, Katherine R. Braylan, Raul C. Yuan, Constance Stetler-Stevenson, Maryalice Arthur, Diane C. Steinberg, Seth M. Figg, William D. Choyke, Peter Landgren, Ola TI Minimal Residual Disease (MRD) Testing in Newly Diagnosed Multiple myeloma (MM) Patients: A Prospective Head-to-Head Assessment of Cell-Based, Molecular, and Molecular-Imaging Modalities SO BLOOD LA English DT Meeting Abstract CT 56th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2014 CL San Francisco, CA SP Amer Soc Hematol C1 [Korde, Neha; Landgren, Ola] Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. [Mailankody, Sham; Roschewski, Mark; Tageja, Nishant; Costello, Rene; Zhang, Yong; Zingone, Adriana; Mulquin, Marcia; Carpenter, Ashley; Zuchlinski, Diamond; Carter, George; Stetler-Stevenson, Maryalice; Choyke, Peter] NCI, NIH, Bethesda, MD 20892 USA. [Faham, Malek; Moorhead, Martin] Sequenta Inc, San Francisco, CA USA. [Kotwaliwale, Chitra] Sequenta Inc, San Francisco, CA USA. [Kwok, Mary L.] Walter Reed Natl Mil Med Ctr, Bethesda, MD USA. [Manasanch, Elisabet E.] Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA. [Bhutani, Manisha; Kazandjian, Dickran; Burton, Debbie; Lamping, Elizabeth; Morrison, Candis; Kurdziel, Karen; Lindenberg, Maria; Kurlander, Roger; Maric, Irina; Calvo, Katherine R.; Braylan, Raul C.; Yuan, Constance; Arthur, Diane C.] NIH, Bethesda, MD 20892 USA. [Steinberg, Seth M.; Figg, William D.] NCI, Bethesda, MD 20892 USA. RI Figg Sr, William/M-2411-2016 NR 0 TC 1 Z9 1 U1 0 U2 1 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 2021 L ST NW, SUITE 900, WASHINGTON, DC 20036 USA SN 0006-4971 EI 1528-0020 J9 BLOOD JI Blood PD DEC 6 PY 2014 VL 124 IS 21 PG 3 WC Hematology SC Hematology GA CA9KX UT WOS:000349243506062 ER PT J AU Korde, N Dosani, T Simakova, O Mailankody, S Costello, R Roschewski, M Yuan, C Stetler-Stevenson, M Figg, WD Landgren, O Maric, I AF Korde, Neha Dosani, Talib Simakova, Olga Mailankody, Sham Costello, Rene Roschewski, Mark Yuan, Constance Stetler-Stevenson, Maryalice Figg, William D. Landgren, Ola Maric, Irina TI Biomarker Proteasome Levels Predict Response to Combination Therapy with Carfilzomib, Lenalidomide, and Dexamethasone in Newly Diagnosed Multiple Myeloma Patients SO BLOOD LA English DT Meeting Abstract CT 56th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2014 CL San Francisco, CA SP Amer Soc Hematol C1 [Korde, Neha; Landgren, Ola] Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. [Simakova, Olga] NIH, Ctr Clin, Bethesda, MD 20892 USA. [Mailankody, Sham; Costello, Rene; Roschewski, Mark; Stetler-Stevenson, Maryalice] NCI, NIH, Bethesda, MD 20892 USA. [Yuan, Constance; Maric, Irina] NIH, Bethesda, MD 20892 USA. [Figg, William D.] NCI, Bethesda, MD 20892 USA. RI Figg Sr, William/M-2411-2016 NR 0 TC 0 Z9 0 U1 0 U2 2 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 2021 L ST NW, SUITE 900, WASHINGTON, DC 20036 USA SN 0006-4971 EI 1528-0020 J9 BLOOD JI Blood PD DEC 6 PY 2014 VL 124 IS 21 PG 3 WC Hematology SC Hematology GA CA9KX UT WOS:000349243505190 ER PT J AU Korde, N Mailankody, S Arons, E Braylan, RC Raffeld, M Maestri, E Yuan, C Stetler-Stevenson, M Landgren, O Maric, I Kreitman, RJ AF Korde, Neha Mailankody, Sham Arons, Evgeny Braylan, Raul C. Raffeld, Mark Maestri, Elizabeth Yuan, Constance Stetler-Stevenson, Maryalice Landgren, Ola Maric, Irina Kreitman, Robert J. TI Series of Hairy Cell Leukemia Patients with Co-Existent Plasma Cell Disorders SO BLOOD LA English DT Meeting Abstract CT 56th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2014 CL San Francisco, CA SP Amer Soc Hematol C1 [Korde, Neha; Landgren, Ola] Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. [Mailankody, Sham; Arons, Evgeny; Raffeld, Mark; Kreitman, Robert J.] NCI, NIH, Bethesda, MD 20892 USA. [Braylan, Raul C.; Yuan, Constance; Stetler-Stevenson, Maryalice; Maric, Irina] NIH, Bethesda, MD USA. [Maestri, Elizabeth] Mol Biol Lab, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 2021 L ST NW, SUITE 900, WASHINGTON, DC 20036 USA SN 0006-4971 EI 1528-0020 J9 BLOOD JI Blood PD DEC 6 PY 2014 VL 124 IS 21 PG 3 WC Hematology SC Hematology GA CA9HU UT WOS:000349233804213 ER PT J AU Krivega, I Byrnes, C de Vasconcellos, JF Lee, YT Kaushal, M Dean, A Miller, JL AF Krivega, Ivan Byrnes, Colleen de Vasconcellos, Jaira F. Lee, Y. Terry Kaushal, Megha Dean, Ann Miller, Jeffery L. TI Inhibition of G9a Methyltransferase in Adult Human Erythroblasts Stimulates Fetal Hemoglobin Production By Facilitating Looping Between LCR and gamma-Globin Gene SO BLOOD LA English DT Meeting Abstract CT 56th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2014 CL San Francisco, CA SP Amer Soc Hematol C1 [Krivega, Ivan; Byrnes, Colleen; de Vasconcellos, Jaira F.; Lee, Y. Terry; Kaushal, Megha; Dean, Ann; Miller, Jeffery L.] NIDDK, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 2021 L ST NW, SUITE 900, WASHINGTON, DC 20036 USA SN 0006-4971 EI 1528-0020 J9 BLOOD JI Blood PD DEC 6 PY 2014 VL 124 IS 21 PG 3 WC Hematology SC Hematology GA CA9KX UT WOS:000349243501210 ER PT J AU Kumkhaek, C Shriner, D Doumatey, AP Rotimi, CN Rodgers, GP AF Kumkhaek, Chutima Shriner, Daniel Doumatey, Ayo P. Rotimi, Charles N. Rodgers, Griffin P. TI An Intergenic SNP in the beta-globin Gene Cluster Is Associated with Hyperuricemia and Influences Gene Transcription in Vitro SO BLOOD LA English DT Meeting Abstract CT 56th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2014 CL San Francisco, CA SP Amer Soc Hematol C1 [Kumkhaek, Chutima; Rodgers, Griffin P.] NHLBI, NIH, Bethesda, MD 20892 USA. [Shriner, Daniel; Doumatey, Ayo P.; Rotimi, Charles N.] NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 2021 L ST NW, SUITE 900, WASHINGTON, DC 20036 USA SN 0006-4971 EI 1528-0020 J9 BLOOD JI Blood PD DEC 6 PY 2014 VL 124 IS 21 PG 2 WC Hematology SC Hematology GA CA9KX UT WOS:000349243506204 ER PT J AU Landgren, O Roschewski, M Mailankody, S Kwok, M Manasanch, EE Bhutani, M Tageja, N Kazandjian, D Zingone, A Costello, R Burton, D Zhang, Y Wu, P Carter, G Mulquin, M Zuchlinski, D Carpenter, A Gounden, V Morrison, C Maric, I Calvo, KR Braylan, RC Yuan, C Stetler-Stevenson, M Arthur, DC Lindenberg, L Karen, K Choyke, P Steinberg, SM Figg, WD Korde, N AF Landgren, Ola Roschewski, Mark Mailankody, Sham Kwok, Mary Manasanch, Elisabet E. Bhutani, Manisha Tageja, Nishant Kazandjian, Dickran Zingone, Adriana Costello, Rene Burton, Debra Zhang, Yong Wu, Peter Carter, George Mulquin, Marcia Zuchlinski, Diamond Carpenter, Ashley Gounden, Verena Morrison, Candice Maric, Irina Calvo, Katherine R. Braylan, Raul C. Yuan, Constance Stetler-Stevenson, Maryalice Arthur, Diane C. Lindenberg, Liza Karen, Kurdziel Choyke, Peter Steinberg, Seth M. Figg, William D. Korde, Neha TI Carfilzomib, Lenalidomide, and Dexamethasone in HighRisk Smoldering Multiple Myeloma: Final Results from the NCI Phase 2 Pilot Study SO BLOOD LA English DT Meeting Abstract CT 56th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2014 CL San Francisco, CA SP Amer Soc Hematol C1 [Landgren, Ola; Korde, Neha] Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. [Landgren, Ola; Roschewski, Mark; Mailankody, Sham; Kwok, Mary; Bhutani, Manisha; Tageja, Nishant; Kazandjian, Dickran; Zingone, Adriana; Costello, Rene; Burton, Debra; Zhang, Yong; Wu, Peter; Carter, George; Mulquin, Marcia; Zuchlinski, Diamond; Carpenter, Ashley; Morrison, Candice; Stetler-Stevenson, Maryalice; Karen, Kurdziel; Choyke, Peter; Korde, Neha] NCI, NIH, Bethesda, MD 20892 USA. [Manasanch, Elisabet E.] Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA. [Gounden, Verena; Maric, Irina; Calvo, Katherine R.; Braylan, Raul C.; Yuan, Constance; Arthur, Diane C.; Lindenberg, Liza] NIH, Bethesda, MD 20892 USA. [Steinberg, Seth M.; Figg, William D.] NCI, Bethesda, MD 20892 USA. RI Figg Sr, William/M-2411-2016 NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 2021 L ST NW, SUITE 900, WASHINGTON, DC 20036 USA SN 0006-4971 EI 1528-0020 J9 BLOOD JI Blood PD DEC 6 PY 2014 VL 124 IS 21 PG 3 WC Hematology SC Hematology GA CA9KX UT WOS:000349243501164 ER PT J AU Lee, DW Stetler-Stevenson, M Sabatino, M Yuan, C Fry, TJ Shah, NN Delbrook, C Yates, B Zhang, H Zhang, L Tschernia, N Cui, YZ Feldman, S Kochenderfer, JN Rosenberg, SA Stroncek, DF Wayne, AS Mackall, CL AF Lee, Daniel W. Stetler-Stevenson, Maryalice Sabatino, Marianna Yuan, Constance Fry, Terry J. Shah, Nirali N. Delbrook, Cindy Yates, Bonnie Zhang, Hua Zhang, Ling Tschernia, Nick Cui, Yongzhi Feldman, Steven Kochenderfer, James N. Rosenberg, Steven A. Stroncek, David F. Wayne, Alan S. Mackall, Crystal L. TI Intent-to-Treat Results of a Phase I Trial of CD19 Chimeric Antigen Receptor Engineered T Cells Using a Consistent Treatment Regimen Reveals a 67% Complete Response Rate in Relapsed, Refractory Acute Lymphoblastic Leukemia SO BLOOD LA English DT Meeting Abstract CT 56th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2014 CL San Francisco, CA SP Amer Soc Hematol C1 [Lee, Daniel W.; Stetler-Stevenson, Maryalice; Fry, Terry J.; Yates, Bonnie; Zhang, Hua; Zhang, Ling; Tschernia, Nick; Cui, Yongzhi; Wayne, Alan S.; Mackall, Crystal L.] NCI, NIH, Bethesda, MD 20892 USA. [Sabatino, Marianna; Yuan, Constance; Shah, Nirali N.; Delbrook, Cindy] NIH, Bethesda, MD 20892 USA. [Feldman, Steven; Kochenderfer, James N.; Rosenberg, Steven A.] NCI, Bethesda, MD 20892 USA. [Stroncek, David F.] NIH, Ctr Clin, Bethesda, MD 20892 USA. [Wayne, Alan S.] Univ So Calif, Keck Sch Med, Childrens Hosp Los Angeles, Los Angeles, CA 90033 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 2021 L ST NW, SUITE 900, WASHINGTON, DC 20036 USA SN 0006-4971 EI 1528-0020 J9 BLOOD JI Blood PD DEC 6 PY 2014 VL 124 IS 21 PG 3 WC Hematology SC Hematology GA CA9HU UT WOS:000349233808086 ER PT J AU Lee, YT Byrnes, C de Vasconcellos, JF Kaushal, M Rabel, A Tumburu, L Allwardt, JM Miller, JL AF Lee, Y. Terry Byrnes, Colleen de Vasconcellos, Jaira F. Kaushal, Megha Rabel, Antoinette Tumburu, Laxminath Allwardt, Joshua M. Miller, Jeffery L. TI Erythroid-Specific Expression of LIN28A Is Sufficient for Robust Gamma-Globin Gene and Protein Expression in Adult Erythroblasts SO BLOOD LA English DT Meeting Abstract CT 56th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2014 CL San Francisco, CA SP Amer Soc Hematol C1 [Lee, Y. Terry; Byrnes, Colleen; de Vasconcellos, Jaira F.; Kaushal, Megha; Rabel, Antoinette; Tumburu, Laxminath; Allwardt, Joshua M.; Miller, Jeffery L.] Natl Inst Diabet & Digest & Kidney Dis, NIH, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 2021 L ST NW, SUITE 900, WASHINGTON, DC 20036 USA SN 0006-4971 EI 1528-0020 J9 BLOOD JI Blood PD DEC 6 PY 2014 VL 124 IS 21 PG 3 WC Hematology SC Hematology GA CA9HU UT WOS:000349233803045 ER PT J AU Lund, SH Hultcrantz, M Goldin, L Landgren, O Bjorkholm, M Turesson, I Kristinsson, SY AF Lund, Sigrun Helga Hultcrantz, Malin Goldin, Lynn Landgren, Ola Bjorkholm, Magnus Turesson, Ingemar Kristinsson, Sigurdur Y. TI Patterns of Infectious Morbidity in Patients with Waldenstrom's Macroglobulinaemia/Lymphoplasmacytic Lymphoma: A Population-Based Study SO BLOOD LA English DT Meeting Abstract CT 56th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2014 CL San Francisco, CA SP Amer Soc Hematol C1 [Lund, Sigrun Helga] Univ Iceland, Reykjavik, Iceland. [Hultcrantz, Malin; Bjorkholm, Magnus; Kristinsson, Sigurdur Y.] Karolinska Univ Hosp, Stockholm, Sweden. [Hultcrantz, Malin; Bjorkholm, Magnus; Kristinsson, Sigurdur Y.] Karolinska Inst, Stockholm, Sweden. [Goldin, Lynn] NCI, NIH, Bethesda, MD 20892 USA. [Landgren, Ola] Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. [Turesson, Ingemar] Skane Univ Hosp, Malmo, Sweden. [Kristinsson, Sigurdur Y.] Fac Med, Reykjavik, Iceland. RI Kristinsson, Sigurdur /M-2910-2015 OI Kristinsson, Sigurdur /0000-0002-4964-7476 NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 2021 L ST NW, SUITE 900, WASHINGTON, DC 20036 USA SN 0006-4971 EI 1528-0020 J9 BLOOD JI Blood PD DEC 6 PY 2014 VL 124 IS 21 PG 3 WC Hematology SC Hematology GA CA9KX UT WOS:000349243507154 ER PT J AU Mast, AE Kiss, J Cable, RG Glynn, S Brambilla, D AF Mast, Alan E. Kiss, Joseph Cable, Ritchard G. Glynn, Simone Brambilla, Donald CA NHLBI Recipient Epidemiology Donor TI Effects of Storage Iron on Erythropoietin and Hepcidin Responses to Acute Hemorrhage SO BLOOD LA English DT Meeting Abstract CT 56th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2014 CL San Francisco, CA SP Amer Soc Hematol C1 [Mast, Alan E.] Blood Ctr Wisconsin, Milwaukee, WI USA. [Kiss, Joseph] Univ Pittsburgh, Pittsburgh, PA USA. [Kiss, Joseph] Inst Transfus Med, Pittsburgh, PA USA. [Cable, Ritchard G.] Amer Red Cross, Farmington, CT USA. [Glynn, Simone] NHLBI, Bethesda, MD 20892 USA. [NHLBI Recipient Epidemiology Donor] RTI, Rockville, MD USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 2021 L ST NW, SUITE 900, WASHINGTON, DC 20036 USA SN 0006-4971 EI 1528-0020 J9 BLOOD JI Blood PD DEC 6 PY 2014 VL 124 IS 21 PG 3 WC Hematology SC Hematology GA CA9HU UT WOS:000349233805228 ER PT J AU Matas-Cespedes, A Vidal-Crespo, A Rodriguez, V Delgado, J Villamor, N Roue, G Campo, E Colomer, D Doshi, P Wiestner, A Parren, PWHI van Bueren, JL Perez-Galan, P AF Matas-Cespedes, Alba Vidal-Crespo, Anna Rodriguez, Vanina Delgado, Julio Villamor, Neus Roue, Gael Campo, Elas Colomer, Dolors Doshi, Parul Wiestner, Adrian Parren, Paul W. H. I. van Bueren, Jeroen Lammerts Perez-Galan, Patricia TI Daratumumab, a Novel Anti-CD38 Monoclonal Antibody Shows Anti- Tumor Activity in CLL and hampers Leukemia-Microenvironment Interactions SO BLOOD LA English DT Meeting Abstract CT 56th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2014 CL San Francisco, CA SP Amer Soc Hematol C1 [Matas-Cespedes, Alba; Vidal-Crespo, Anna; Rodriguez, Vanina; Roue, Gael; Perez-Galan, Patricia] IDIBAPS, Barcelona, Spain. [Delgado, Julio; Villamor, Neus; Colomer, Dolors] Hosp Clin IDIBAPS, Barcelona, Spain. [Campo, Elas] Hosp Clin Barcelona, Barcelona, Spain. [Doshi, Parul] Janssen Res & Dev, Spring House, PA USA. [Wiestner, Adrian] NHLBI, NIH, Bethesda, MD 20892 USA. [Parren, Paul W. H. I.; van Bueren, Jeroen Lammerts] Genmab BV, Utrecht, Netherlands. RI Delgado, Julio/D-4891-2013; Roue, Gael/D-4759-2014 OI Delgado, Julio/0000-0002-5157-4376; Roue, Gael/0000-0003-0245-2257 NR 0 TC 0 Z9 0 U1 0 U2 2 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 2021 L ST NW, SUITE 900, WASHINGTON, DC 20036 USA SN 0006-4971 EI 1528-0020 J9 BLOOD JI Blood PD DEC 6 PY 2014 VL 124 IS 21 PG 3 WC Hematology SC Hematology GA CA9HU UT WOS:000349233802087 ER PT J AU Miner, S Hensel, NF Salem, B Dunavin, N Tanimoto, K Battiwalla, M Lu, K Keyvanfar, K Sabatino, M Stroncek, D Hanley, PJ Bollard, CM Rezvani, K Kortylewski, M Muranski, P Barrett, J Ito, S AF Miner, Samantha Hensel, Nancy F. Salem, Bahey Dunavin, Neil Tanimoto, Kazushi Battiwalla, Minoo Lu, Kit Keyvanfar, Keyvan Sabatino, Marianna Stroncek, David Hanley, Patrick J. Bollard, Catherine M. Rezvani, Katayoun Kortylewski, Marcin Muranski, Pawel Barrett, John Ito, Sawa TI A Novel Standardized Quantitative Suppression Assay Reveals a Diversity of Human Immune-Regulatory Cell Potency SO BLOOD LA English DT Meeting Abstract CT 56th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2014 CL San Francisco, CA SP Amer Soc Hematol C1 [Miner, Samantha; Hensel, Nancy F.; Salem, Bahey; Dunavin, Neil; Tanimoto, Kazushi; Battiwalla, Minoo; Keyvanfar, Keyvan; Muranski, Pawel; Barrett, John; Ito, Sawa] NHLBI, NIH, Bethesda, MD 20892 USA. [Lu, Kit] NHLBI, Hematol Branch, NIH, Bethesda, MD 20892 USA. [Sabatino, Marianna; Stroncek, David] NIH, Bethesda, MD 20892 USA. [Hanley, Patrick J.] Sheikh Zayed Inst Pediat Surg Innovat, Program Cell Enhancement & Technol Immunotherapy, Washington, DC USA. [Hanley, Patrick J.] Childrens Natl Hlth Syst, Ctr Canc & Immunol Res, Washington, DC USA. [Bollard, Catherine M.] Childrens Natl Med Ctr, Washington, DC 20010 USA. [Rezvani, Katayoun] Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA. [Kortylewski, Marcin] City Hope Natl Med Ctr, Duarte, CA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 2021 L ST NW, SUITE 900, WASHINGTON, DC 20036 USA SN 0006-4971 EI 1528-0020 J9 BLOOD JI Blood PD DEC 6 PY 2014 VL 124 IS 21 PG 3 WC Hematology SC Hematology GA CA9KX UT WOS:000349243501205 ER PT J AU Minniti, CP Kato, GJ Nouraie, M Alam, S Campbell, A Rana, SR Darbari, D Castro, OL Gordeuk, VR AF Minniti, Caterina P. Kato, Gregory J. Nouraie, Mehdi Alam, Shoaib Campbell, Andrew Rana, Sohail R. Darbari, Deepika Castro, Oswaldo L. Gordeuk, Victor R. TI Cardiopulmonary Functional Status in Children with SCD at Baseline: Pulse Pressure As a Biomarker of Early Compromise SO BLOOD LA English DT Meeting Abstract CT 56th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2014 CL San Francisco, CA SP Amer Soc Hematol C1 [Minniti, Caterina P.; Alam, Shoaib] NHLBI, Bethesda, MD 20892 USA. [Kato, Gregory J.] NHLBI, NIH, Bethesda, MD 20892 USA. [Nouraie, Mehdi; Rana, Sohail R.; Castro, Oswaldo L.] Howard Univ, Washington, DC 20059 USA. [Campbell, Andrew] Univ Michigan, Ann Arbor, MI 48109 USA. [Darbari, Deepika] NHLBI, Childrens Natl Med Ctr, Washington, DC USA. [Gordeuk, Victor R.] Univ Illinois, Chicago, IL USA. RI Kato, Gregory/I-7615-2014 OI Kato, Gregory/0000-0003-4465-3217 NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 2021 L ST NW, SUITE 900, WASHINGTON, DC 20036 USA SN 0006-4971 EI 1528-0020 J9 BLOOD JI Blood PD DEC 6 PY 2014 VL 124 IS 21 PG 3 WC Hematology SC Hematology GA CA9HU UT WOS:000349233801119 ER PT J AU Mirsoian, A Bouchlaka, MN Sckisel, G Chen, MY Pai, CCS Maverakis, E Spencer, R Fishbein, K Siddiqui, S Monjazeb, A Martin, B Maudsley, S Hesdorffer, C Ferrucci, L Longo, DL Blazar, BR Wiltrout, R Taub, DD Murphy, WJ AF Mirsoian, Annie Bouchlaka, Myriam N. Sckisel, Gail Chen, Mingyi Pai, Chien-Chun Steven Maverakis, Emanuel Spencer, Richard Fishbein, Kenneth Siddiqui, Sana Monjazeb, Arta Martin, Bronwen Maudsley, Stuart Hesdorffer, Charles Ferrucci, Luigi Longo, Dan L. Blazar, Bruce R. Wiltrout, Robert Taub, Dennis D. Murphy, William J. TI Adiposity As a Principal Component of Lethal Cytokine Storm Following Cancer Immunotherapy in Aged Mice SO BLOOD LA English DT Meeting Abstract CT 56th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2014 CL San Francisco, CA SP Amer Soc Hematol C1 [Mirsoian, Annie; Pai, Chien-Chun Steven; Monjazeb, Arta; Murphy, William J.] Univ Calif Davis, Sacramento, CA 95817 USA. [Bouchlaka, Myriam N.] Univ Wisconsin, Madison, WI USA. [Sckisel, Gail; Maverakis, Emanuel] UC Davis Sch Med, Sacramento, CA USA. [Chen, Mingyi] UC Davis Med Ctr, Sacramento, CA USA. [Spencer, Richard; Fishbein, Kenneth; Siddiqui, Sana; Martin, Bronwen; Maudsley, Stuart; Ferrucci, Luigi; Taub, Dennis D.] NIA, IRP, NIH, Baltimore, MD 21224 USA. [Hesdorffer, Charles] NIA, Baltimore, MD 21224 USA. [Longo, Dan L.] NIA, NIH, Baltimore, MD 21224 USA. [Blazar, Bruce R.] Univ Minnesota, Minneapolis, MN USA. [Wiltrout, Robert] NCI, Frederick, MD 21701 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 2021 L ST NW, SUITE 900, WASHINGTON, DC 20036 USA SN 0006-4971 EI 1528-0020 J9 BLOOD JI Blood PD DEC 6 PY 2014 VL 124 IS 21 PG 3 WC Hematology SC Hematology GA CA9HU UT WOS:000349233807033 ER PT J AU Moriaitis, A Freeman, L Shamburek, R Wesley, R Wilson, WH Grant, C Price, S Thacker, S Zarzour, A Pucino, F Csako, G Yarboro, C McInnes, I Kuroiwa, T Boumpas, D Illei, G Remaley, AT Rao, VK AF Moriaitis, Andreas Freeman, Lita Shamburek, Robert Wesley, Robert Wilson, Wyndham H. Grant, Cliona Price, Susan Thacker, Seth Zarzour, Abdalrahman Pucino, Frank Csako, Gyorgy Yarboro, Cheryl McInnes, Iain Kuroiwa, Takashi Boumpas, Dimitrios Illei, Gabor Remaley, Alan T. Rao, V. Koneti TI Elevated Interleukin-10 and "Disappearing HDL Syndrome" in Lymphoproliferative Disorders SO BLOOD LA English DT Meeting Abstract CT 56th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2014 CL San Francisco, CA SP Amer Soc Hematol C1 [Moriaitis, Andreas] Univ Michigan, Ann Arbor, MI 48109 USA. [Freeman, Lita; Shamburek, Robert; Thacker, Seth; Zarzour, Abdalrahman; Csako, Gyorgy; McInnes, Iain; Remaley, Alan T.] NHLBI, NIH, Bethesda, MD 20892 USA. [Wesley, Robert; Pucino, Frank; Yarboro, Cheryl; Kuroiwa, Takashi; Boumpas, Dimitrios; Illei, Gabor] NIAMS, NIH, Bethesda, MD USA. [Wilson, Wyndham H.] NCI, Bethesda, MD 20892 USA. [Grant, Cliona] NIH, Bethesda, MD 20892 USA. [Price, Susan; Rao, V. Koneti] NIAID, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 2021 L ST NW, SUITE 900, WASHINGTON, DC 20036 USA SN 0006-4971 EI 1528-0020 J9 BLOOD JI Blood PD DEC 6 PY 2014 VL 124 IS 21 PG 3 WC Hematology SC Hematology GA CA9KX UT WOS:000349243507039 ER PT J AU Noji, H Shichishima, T Sugimori, C Obara, N Hosokawa, K Chiba, S Nakamura, Y Ando, K Hayashi, S Yonemura, Y Kawaguchi, T Ninomiya, H Nishimura, J Kanakura, Y Nakao, S AF Noji, Hideyoshi Shichishima, Tsutomu Sugimori, Chiharu Obara, Naoshi Hosokawa, Kohei Chiba, Shigeru Nakamura, Yoshihiko Ando, Kiyoshi Hayashi, Satoru Yonemura, Yuji Kawaguchi, Tatsuya Ninomiya, Haruhiko Nishimura, Jun-ichi Kanakura, Yuzuru Nakao, Shinji TI The Interim Analysis of the Optima (observation of GPI-anchored protein-deficient [PNH-type]) Cells in Japanese Patients with Bone Marrow Failure Syndrome and in Those Suspected of Having PNH) Study SO BLOOD LA English DT Meeting Abstract CT 56th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2014 CL San Francisco, CA SP Amer Soc Hematol C1 [Noji, Hideyoshi; Shichishima, Tsutomu] Fukushima Med Univ, Fukushima, Japan. [Noji, Hideyoshi; Shichishima, Tsutomu; Sugimori, Chiharu; Obara, Naoshi; Hosokawa, Kohei; Chiba, Shigeru; Nakamura, Yoshihiko; Ando, Kiyoshi; Hayashi, Satoru; Yonemura, Yuji; Kawaguchi, Tatsuya; Ninomiya, Haruhiko; Nishimura, Jun-ichi; Kanakura, Yuzuru; Nakao, Shinji] Japan PNH Study Grp, Tokyo, Japan. [Shichishima, Tsutomu] Fukushima Res Inst Environm & Med, Fukushima, Japan. [Sugimori, Chiharu] Ishikawa Prefectural Cent Hosp, Kanazawa, Ishikawa, Japan. [Obara, Naoshi; Chiba, Shigeru; Ninomiya, Haruhiko] Univ Tsukuba, Tsukuba, Ibaraki, Japan. [Hosokawa, Kohei] NHLBI, Hematol Branch, NIH, Bethesda, MD 20892 USA. [Nakamura, Yoshihiko; Ando, Kiyoshi] Tokai Univ, Sch Med, Isehara, Kanagawa 25911, Japan. [Hayashi, Satoru; Nishimura, Jun-ichi; Kanakura, Yuzuru] Osaka Univ, Grad Sch Med, Suita, Osaka, Japan. [Yonemura, Yuji] Kumamoto Univ Hosp, Kumamoto, Japan. [Kawaguchi, Tatsuya] Kumamoto Univ, Grad Sch Med Sci, Kumamoto, Japan. [Nakao, Shinji] Kanazawa Univ, Grad Sch Med Sci, Kanazawa, Ishikawa, Japan. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 2021 L ST NW, SUITE 900, WASHINGTON, DC 20036 USA SN 0006-4971 EI 1528-0020 J9 BLOOD JI Blood PD DEC 6 PY 2014 VL 124 IS 21 PG 3 WC Hematology SC Hematology GA CA9KX UT WOS:000349243504122 ER PT J AU Novelli, EM Hildesheim, ME Rosano, C Vanderpool, R Simon, M Kato, G Gladwin, MT AF Novelli, Enrico M. Hildesheim, Mariana E. Rosano, Caterina Vanderpool, Rebecca Simon, Marc Kato, Gregory Gladwin, Mark T. TI Elevated Pulse Pressure Is Associated with Hemolysis, Proteinuria and Chronic Kidney Disease in Sickle Cell Disease SO BLOOD LA English DT Meeting Abstract CT 56th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2014 CL San Francisco, CA SP Amer Soc Hematol C1 [Novelli, Enrico M.; Rosano, Caterina; Vanderpool, Rebecca; Simon, Marc; Kato, Gregory; Gladwin, Mark T.] Univ Pittsburgh, Pittsburgh, PA USA. [Hildesheim, Mariana E.] NIH, Bethesda, MD 20892 USA. RI Kato, Gregory/I-7615-2014 OI Kato, Gregory/0000-0003-4465-3217 NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 2021 L ST NW, SUITE 900, WASHINGTON, DC 20036 USA SN 0006-4971 EI 1528-0020 J9 BLOOD JI Blood PD DEC 6 PY 2014 VL 124 IS 21 PG 2 WC Hematology SC Hematology GA CA9KX UT WOS:000349243500162 ER PT J AU Pedersen, MB Hamilton-Dutoit, SJ Bendix, K Norgaard, PH Michael, MB Raffeld, M Pittaluga, S Steiniche, T Bergmann, A Vater, I Siebert, R Chan, WC d'Amore, F AF Pedersen, Martin Bjerregaard Hamilton-Dutoit, Stephen Jacques Bendix, Knud Norgaard, Peter H. Michael, Moller Boe Raffeld, Mark Pittaluga, Stefania Steiniche, Torben Bergmann, Anke Vater, Inga Siebert, Reiner Chan, Wing-Chung d'Amore, Francesco TI Identification of a Subset of Peripheral T-Cell Lymphoma, Not Otherwise Specified, Characterized By FOXP3-Positive Regulatory T-Cell Phenotype, HTLV-1 Negativity and Poor Outcome SO BLOOD LA English DT Meeting Abstract CT 56th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2014 CL San Francisco, CA SP Amer Soc Hematol C1 [Pedersen, Martin Bjerregaard; Hamilton-Dutoit, Stephen Jacques; Bendix, Knud; Steiniche, Torben; d'Amore, Francesco] Aarhus Univ Hosp, DK-8000 Aarhus C, Denmark. [Norgaard, Peter H.] Copenhagen Univ Hosp Herlev, Herlev, Denmark. [Michael, Moller Boe] Odense Univ Hosp, DK-5000 Odense, Denmark. [Raffeld, Mark; Pittaluga, Stefania] NCI, Bethesda, MD 20892 USA. [Bergmann, Anke; Vater, Inga; Siebert, Reiner] Univ Kiel, Univ Hosp Schleswig Holstein, Kiel, Germany. [Chan, Wing-Chung] City Hope Natl Med Ctr, Duarte, CA 91010 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 2021 L ST NW, SUITE 900, WASHINGTON, DC 20036 USA SN 0006-4971 EI 1528-0020 J9 BLOOD JI Blood PD DEC 6 PY 2014 VL 124 IS 21 PG 3 WC Hematology SC Hematology GA CA9KX UT WOS:000349243504213 ER PT J AU Perez-Andreu, V Roberts, KG Heng, X Smith, C Zhang, H Yang, WJ Harvey, RC Payne-Turner, D Devidas, M Cheng, IM Carroll, WL Heerema, NA Carroll, AJ Raetz, EA Gastier-Foster, JM Marcucci, G Bloomfield, CD Mrozek, K Kohlschmidt, J Stock, W Kornblau, SM Konopleva, M Paietta, E Rowe, JM Luger, SM Tallman, MS Pui, CH Jeha, S Relling, MV Evans, WE Gerhard, DS Loh, ML Willman, CL Hunger, SP Mullighan, CG Yang, JJ AF Perez-Andreu, Virginia Roberts, Kathryn G. Heng, Xu Smith, Colton Zhang, Hui Yang, Wenjian Harvey, Richard C. Payne-Turner, Debbie Devidas, Meenakshi Cheng, I-Ming Carroll, William L. Heerema, Nyla A. Carroll, Andrew J. Raetz, Elizabeth A. Gastier-Foster, Julie M. Marcucci, Guido Bloomfield, Clara D. Mrozek, Krzysztof Kohlschmidt, Jessica Stock, Wendy Kornblau, Steven M. Konopleva, Marina Paietta, Elisabeth Rowe, Jacob M. Luger, Selina M. Tallman, Martin S. Pui, Ching-Hon Jeha, Sima Relling, Mary V. Evans, William E. Gerhard, Daniela S. Loh, Mignon L. Willman, Cheryl L. Hunger, Stephen P. Mullighan, Charles G. Yang, Jun J. TI A Genome-Wide Association Study of Susceptibility to Acute Lymphoblastic Leukemia in Adolescents and Young Adults SO BLOOD LA English DT Meeting Abstract CT 56th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2014 CL San Francisco, CA SP Amer Soc Hematol C1 [Perez-Andreu, Virginia; Roberts, Kathryn G.; Heng, Xu; Smith, Colton; Zhang, Hui; Yang, Wenjian; Payne-Turner, Debbie; Pui, Ching-Hon; Jeha, Sima; Relling, Mary V.; Evans, William E.; Mullighan, Charles G.; Yang, Jun J.] St Jude Childrens Res Hosp, Memphis, TN 38105 USA. [Heng, Xu] Sichuan Univ, West China Med Sch, West China Hosp, Chengdu 610064, Peoples R China. [Harvey, Richard C.] Univ New Mexico, Ctr Canc, Albuquerque, NM 87131 USA. [Devidas, Meenakshi] Univ Florida, Gainesville, FL USA. [Cheng, I-Ming; Willman, Cheryl L.] Univ New Mexico, Albuquerque, NM 87131 USA. [Carroll, William L.] NYU, Langone Med Ctr, New York, NY USA. [Heerema, Nyla A.; Marcucci, Guido; Bloomfield, Clara D.; Mrozek, Krzysztof; Kohlschmidt, Jessica] Ohio State Univ, Columbus, OH 43210 USA. [Carroll, Andrew J.] Univ Alabama Birmingham, Birmingham, AL USA. [Raetz, Elizabeth A.] Univ Utah, Salt Lake City, UT USA. [Gastier-Foster, Julie M.] Nationwide Childrens Hosp, Columbus, OH USA. [Kohlschmidt, Jessica] Mayo Clin, Rochester, MN USA. [Stock, Wendy] Univ Chicago, Chicago, IL 60637 USA. [Kornblau, Steven M.; Konopleva, Marina] Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA. [Paietta, Elisabeth] Albert Einstein Coll Med, Bronx, NY USA. [Rowe, Jacob M.] Rambam Med Ctr, Haifa, Israel. [Luger, Selina M.] Univ Penn, Hematol Oncol Div, Hematol Malignancies Program, Philadelphia, PA 19104 USA. [Tallman, Martin S.] Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. [Gerhard, Daniela S.; Loh, Mignon L.] NCI, Bethesda, MD 20892 USA. [Hunger, Stephen P.] Univ Colorado, Sch Med, Aurora, CO USA. RI Mrozek, Krzysztof/A-3142-2008 NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 2021 L ST NW, SUITE 900, WASHINGTON, DC 20036 USA SN 0006-4971 EI 1528-0020 J9 BLOOD JI Blood PD DEC 6 PY 2014 VL 124 IS 21 PG 3 WC Hematology SC Hematology GA CA9HU UT WOS:000349233800126 ER PT J AU Pollyea, DA Coutre, S Gore, L Adler, N Harris, P Phelps, MA Johnson, AJ Ling, YH Li, H Gutman, JA Byrd, JC AF Pollyea, Daniel A. Coutre, Steven Gore, Lia Adler, Nichole Harris, Pamela Phelps, Mitch A. Johnson, Amy J. Ling, YongHua Li, Hao Gutman, Jonathan A. Byrd, John C. TI A Dose Escalation Study of Ibrutinib with Lenalidomide for Relapsed and Refractory Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma SO BLOOD LA English DT Meeting Abstract CT 56th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2014 CL San Francisco, CA SP Amer Soc Hematol C1 [Pollyea, Daniel A.; Gutman, Jonathan A.] Univ Colorado, Ctr Canc, Aurora, CO USA. [Coutre, Steven] Stanford Univ, Sch Med, Stanford, CA 94305 USA. [Gore, Lia; Adler, Nichole] Univ Colorado, Aurora, CO USA. [Harris, Pamela] NCI, Rockville, MD USA. [Phelps, Mitch A.; Ling, YongHua; Li, Hao] Ohio State Univ, Columbus, OH 43210 USA. [Johnson, Amy J.] Ohio State Univ, Ctr Comprehens Canc, Columbus, OH 43210 USA. [Byrd, John C.] Ohio State Univ, Med Ctr, Columbus, OH 43210 USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 2021 L ST NW, SUITE 900, WASHINGTON, DC 20036 USA SN 0006-4971 EI 1528-0020 J9 BLOOD JI Blood PD DEC 6 PY 2014 VL 124 IS 21 PG 3 WC Hematology SC Hematology GA CA9KX UT WOS:000349243501111 ER PT J AU Ponce, DM Sparapani, R Chen, JF Rocha, V Fowler, DH Eapen, M Barker, JN Perales, MA AF Ponce, Doris M. Sparapani, Rodney Chen, Junfang Rocha, Vanderson Fowler, Daniel H. Eapen, Mary Barker, Juliet N. Perales, Miguel-Angel TI Comparable 3-Year Disease-Free Survival Regardless of Anti-Thymocyte Globulin Inclusion in Pediatric Myeloablative Cord Blood Transplantation for Acute Lymphoblastic Leukemia SO BLOOD LA English DT Meeting Abstract CT 56th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2014 CL San Francisco, CA SP Amer Soc Hematol C1 [Ponce, Doris M.; Barker, Juliet N.; Perales, Miguel-Angel] Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. [Sparapani, Rodney; Chen, Junfang; Eapen, Mary] Med Coll Wisconsin, Milwaukee, WI 53226 USA. [Rocha, Vanderson] Churchill Hosp, Oxford OX3 7LJ, England. [Fowler, Daniel H.] NCI, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 2021 L ST NW, SUITE 900, WASHINGTON, DC 20036 USA SN 0006-4971 EI 1528-0020 J9 BLOOD JI Blood PD DEC 6 PY 2014 VL 124 IS 21 PG 3 WC Hematology SC Hematology GA CA9KX UT WOS:000349243506007 ER PT J AU Purvey, S Purev, E Tian, X Wilder, J Cook, L Ramos, C Cho, E Prince, P Leitman, SF Khuu, H Stroncek, D Reger, RN Aue, G Childs, RW AF Purvey, Sneha Purev, Enkhtsetseg Tian, Xin Wilder, Jennifer Cook, Lisa Ramos, Catalina Cho, Elena Prince, Patricia Leitman, Susan F. Khuu, Hanh Stroncek, David Reger, Robert N. Aue, Georg Childs, Richard W. TI High Incidence of Late, Sustained and Clinically Inconsequential Epstein Barr Virus (EBV) Reactivation Following Combined Unrelated Cord Blood and Haploidentical CD34+Cell Transplantation SO BLOOD LA English DT Meeting Abstract CT 56th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2014 CL San Francisco, CA SP Amer Soc Hematol C1 [Purvey, Sneha] MedStar Washington Hosp Ctr, Washington, DC USA. [Purvey, Sneha; Purev, Enkhtsetseg; Wilder, Jennifer; Cook, Lisa; Ramos, Catalina; Cho, Elena; Prince, Patricia; Leitman, Susan F.; Khuu, Hanh; Stroncek, David; Reger, Robert N.; Aue, Georg; Childs, Richard W.] NIH, Bethesda, MD 20892 USA. [Tian, Xin] NHLBI, Off Biostat Res, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 2021 L ST NW, SUITE 900, WASHINGTON, DC 20036 USA SN 0006-4971 EI 1528-0020 J9 BLOOD JI Blood PD DEC 6 PY 2014 VL 124 IS 21 PG 3 WC Hematology SC Hematology GA CA9KX UT WOS:000349243506146 ER PT J AU Ragni, MV DiMichele, D Hay, CRM Malec, LM Seaman, CD Yabes, J Li, J Butenas, S Brumel-Ziedins, K AF Ragni, Margaret V. DiMichele, Donna Hay, Charles R. M. Malec, Lynn M. Seaman, Craig D. Yabes, Jonathan Li, Jie Butenas, Saulius Brumel-Ziedins, Kathleen TI Thrombin Generation and Bleeding in Hemophilia Inhibitor Patients during Immune Tolerance Induction SO BLOOD LA English DT Meeting Abstract CT 56th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2014 CL San Francisco, CA SP Amer Soc Hematol C1 [Ragni, Margaret V.; Yabes, Jonathan; Li, Jie] Univ Pittsburgh, Pittsburgh, PA USA. [Ragni, Margaret V.] Hemophilia Ctr Western PA, Pittsburgh, PA USA. [DiMichele, Donna] NHLBI, NIH, Bethesda, MD 20892 USA. [Hay, Charles R. M.] Manchester Royal Infirm, Manchester M13 9WL, Lancs, England. [Malec, Lynn M.] UPMC, Childrens Hosp Pittsburgh, Pittsburgh, PA USA. [Seaman, Craig D.] Univ Pittsburgh, Med Ctr, Pittsburgh, PA USA. [Butenas, Saulius; Brumel-Ziedins, Kathleen] Univ Vermont, Colchester, VT USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 2021 L ST NW, SUITE 900, WASHINGTON, DC 20036 USA SN 0006-4971 EI 1528-0020 J9 BLOOD JI Blood PD DEC 6 PY 2014 VL 124 IS 21 PG 3 WC Hematology SC Hematology GA CA9HU UT WOS:000349233800032 ER PT J AU Ramanathan, M Teira, P Battiwalla, M Barrett, AJ Lindemans, CA Auletta, J Ahn, KW Chen, M Riches, ML Boeckh, M AF Ramanathan, Muthalagu Teira, Pierre Battiwalla, Minoo Barrett, A. John Lindemans, Caroline A. Auletta, Jeffery Ahn, Kwang Woo Chen, Min Riches, Marcie L. Boeckh, Michael TI Early CMV Reactivation Still Remains a Cause of Increased Transplant Related Mortality in the Current Era: A CIBMTR Analysis SO BLOOD LA English DT Meeting Abstract CT 56th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2014 CL San Francisco, CA SP Amer Soc Hematol C1 [Ramanathan, Muthalagu] UMass Mem Med Ctr, Worcester, MA USA. [Teira, Pierre] Univ Montreal, Ste Justine Hosp, Montreal, PQ, Canada. [Battiwalla, Minoo] NHLBI, Hematol Branch, NIH, Bethesda, MD 20892 USA. [Barrett, A. John] NIH, Bethesda, MD 20892 USA. [Lindemans, Caroline A.] Univ Med Ctr Utrecht, Utrecht, Netherlands. [Auletta, Jeffery] Nation Wide Hosp, Columbus, OH USA. [Ahn, Kwang Woo; Chen, Min] Med Coll Wisconsin, Milwaukee, WI 53226 USA. [Riches, Marcie L.] Univ S Florida, H Lee Moffitt Canc Ctr, Tampa, FL 33682 USA. [Boeckh, Michael] Fred Hutchinson Canc Res Ctr, Seattle, WA 98104 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 2021 L ST NW, SUITE 900, WASHINGTON, DC 20036 USA SN 0006-4971 EI 1528-0020 J9 BLOOD JI Blood PD DEC 6 PY 2014 VL 124 IS 21 PG 3 WC Hematology SC Hematology GA CA9HU UT WOS:000349233801219 ER PT J AU Rohr, J Guo, SP Hu, DD Bouska, A Gascoyne, RD Rosenwald, A Simone, P Zhang, WW Xiao, WM Wang, C Fu, K Greiner, TC Weisenburger, DD Vose, JM Staudt, LM Berger, F Borgstahl, G Davis, S McKeithan, T Iqbal, J Chan, WC AF Rohr, Joseph Guo, Shuangping Hu, Dongdong Bouska, Alyssa Gascoyne, Randy D. Rosenwald, Andreas Simone, Peter Zhang, Weiwei Xiao, Wenming Wang, Chao Fu, Kai Greiner, Timothy C. Weisenburger, Dennis D. Vose, Julie M. Staudt, Louis M. Berger, Francoise Borgstahl, Gloria Davis, Simon McKeithan, Timothy Iqbal, Javeed Chan, Wing-Chung (John) TI CD28 Mutations in Peripheral T-Cell Lymphomagenesis and Progression SO BLOOD LA English DT Meeting Abstract CT 56th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2014 CL San Francisco, CA SP Amer Soc Hematol C1 [Rohr, Joseph; Bouska, Alyssa; Zhang, Weiwei; Wang, Chao; Fu, Kai; Greiner, Timothy C.; Vose, Julie M.; Borgstahl, Gloria; Iqbal, Javeed] Univ Nebraska Med Ctr, Omaha, NE USA. [Guo, Shuangping] Fourth Mil Med Univ, Xian 710032, Peoples R China. [Hu, Dongdong; Davis, Simon] Univ Oxford, Oxford, England. [Gascoyne, Randy D.] British Columbia Canc Agcy, Vancouver, BC V5Z 4E6, Canada. [Rosenwald, Andreas] Univ Wurzburg, D-97070 Wurzburg, Germany. [Simone, Peter] Florida Atlantic Univ, Boca Raton, FL 33431 USA. [Xiao, Wenming] NIH, Bethesda, MD 20892 USA. [Wang, Chao] Shandong Univ, Jinan 250100, Peoples R China. [Weisenburger, Dennis D.; McKeithan, Timothy; Chan, Wing-Chung (John)] City Hope Natl Med Ctr, Duarte, CA 91010 USA. [Staudt, Louis M.] NCI, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. [Berger, Francoise] Univ Lyon 1, Dept Pathol & Hematol, Hosp Civils Lyon, F-69365 Lyon, France. NR 0 TC 2 Z9 2 U1 0 U2 2 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 2021 L ST NW, SUITE 900, WASHINGTON, DC 20036 USA SN 0006-4971 EI 1528-0020 J9 BLOOD JI Blood PD DEC 6 PY 2014 VL 124 IS 21 PG 3 WC Hematology SC Hematology GA CA9HU UT WOS:000349233804186 ER PT J AU Roschewski, M Dunleavy, K Pittaluga, S Kong, K Shovlin, M Jaffe, ES Staudt, LM Lai, C Chen, CC Zheng, JB Willis, TD Faham, M Wilson, WH AF Roschewski, Mark Dunleavy, Kieron Pittaluga, Stefania Kong, Katie Shovlin, Margaret Jaffe, Elaine S. Staudt, Louis M. Lai, Catherine Chen, Clara C. Zheng, Jianbiao Willis, Thomas D. Faham, Malek Wilson, Wyndham H. TI Monitoring of Circulating Tumor DNA As Minimal Residual Disease in Diffuse Large B-Cell Lymphoma SO BLOOD LA English DT Meeting Abstract CT 56th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2014 CL San Francisco, CA SP Amer Soc Hematol C1 [Roschewski, Mark; Jaffe, Elaine S.; Lai, Catherine] NCI, NIH, Bethesda, MD 20892 USA. [Dunleavy, Kieron; Pittaluga, Stefania] NIH, Bethesda, MD 20892 USA. [Kong, Katie; Zheng, Jianbiao; Willis, Thomas D.; Faham, Malek] Sequenta Inc, San Francisco, CA USA. [Shovlin, Margaret; Staudt, Louis M.; Wilson, Wyndham H.] NCI, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. [Chen, Clara C.] Nucl Med, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 3 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 2021 L ST NW, SUITE 900, WASHINGTON, DC 20036 USA SN 0006-4971 EI 1528-0020 J9 BLOOD JI Blood PD DEC 6 PY 2014 VL 124 IS 21 PG 3 WC Hematology SC Hematology GA CA9HU UT WOS:000349233805073 ER PT J AU Rosenberg, PS Barker, KA Anderson, WF AF Rosenberg, Philip S. Barker, Kimberly A. Anderson, William F. TI Future Burden of Multiple Myeloma in the United States SO BLOOD LA English DT Meeting Abstract CT 56th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2014 CL San Francisco, CA SP Amer Soc Hematol C1 [Rosenberg, Philip S.; Barker, Kimberly A.] NCI, Bethesda, MD 20892 USA. [Anderson, William F.] NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 2 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 2021 L ST NW, SUITE 900, WASHINGTON, DC 20036 USA SN 0006-4971 EI 1528-0020 J9 BLOOD JI Blood PD DEC 6 PY 2014 VL 124 IS 21 PG 3 WC Hematology SC Hematology GA CA9HU UT WOS:000349233805032 ER PT J AU Saba, N Liu, DL Herman, SEM Grant, C Dunleavy, K Pittaluga, S Wilson, W Wiestner, A AF Saba, Nakhle Liu, Delong Herman, Sarah E. M. Grant, Cliona Dunleavy, Kieron Pittaluga, Stefania Wilson, Wyndham Wiestner, Adrian TI Ongoing Activation of the BCR, NF kappa B, and Proliferation Pathways in Mantle Cell Lymphoma: Direct in Vivo Evidence for the Role of the Lymph Node Microenvironnment SO BLOOD LA English DT Meeting Abstract CT 56th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2014 CL San Francisco, CA SP Amer Soc Hematol C1 [Saba, Nakhle] Tulane Univ, New Orleans, LA 70118 USA. [Saba, Nakhle; Liu, Delong; Herman, Sarah E. M.; Grant, Cliona; Dunleavy, Kieron; Pittaluga, Stefania; Wilson, Wyndham; Wiestner, Adrian] NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 2021 L ST NW, SUITE 900, WASHINGTON, DC 20036 USA SN 0006-4971 EI 1528-0020 J9 BLOOD JI Blood PD DEC 6 PY 2014 VL 124 IS 21 PG 3 WC Hematology SC Hematology GA CA9KX UT WOS:000349243504022 ER PT J AU Scott, DW Mottok, A Ennishi, D Wright, GW Farinha, P Ben-Neriah, S Kridel, R Barry, GS Hother, CE Savage, KJ Sehn, LH Staudt, LM Connors, JM Rimsza, LM Gascoyne, RD AF Scott, David W. Mottok, Anja Ennishi, Daisuke Wright, George W. Farinha, Pedro Ben-Neriah, Susana Kridel, Robert Barry, Garrett S. Hother, Christoffer E. Savage, Kerry J. Sehn, Laurie H. Staudt, Louis M. Connors, Joseph M. Rimsza, Lisa M. Gascoyne, Randy D. TI Cell-of-Origin Assignment in Diffuse Large B-Cell Lymphoma Determined By Gene Expression in Formalin-Fixed Paraffin-Embedded Tissue Has Prognostic Significance Independent of IPI and MYC/BCL2 Immunohistochemistry SO BLOOD LA English DT Meeting Abstract CT 56th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2014 CL San Francisco, CA SP Amer Soc Hematol C1 [Scott, David W.; Mottok, Anja; Ennishi, Daisuke; Farinha, Pedro; Ben-Neriah, Susana; Kridel, Robert; Barry, Garrett S.; Hother, Christoffer E.; Savage, Kerry J.; Sehn, Laurie H.; Connors, Joseph M.] British Columbia Canc Agcy, Vancouver, BC V5Z 4E6, Canada. [Wright, George W.] NCI, Bethesda, MD 20892 USA. [Staudt, Louis M.] NCI, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. [Rimsza, Lisa M.] Univ Arizona, Tucson, AZ USA. [Gascoyne, Randy D.] Ctr Lymphoid Canc, Vancouver, BC, Canada. NR 0 TC 1 Z9 1 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 2021 L ST NW, SUITE 900, WASHINGTON, DC 20036 USA SN 0006-4971 EI 1528-0020 J9 BLOOD JI Blood PD DEC 6 PY 2014 VL 124 IS 21 PG 3 WC Hematology SC Hematology GA CA9HU UT WOS:000349233800112 ER PT J AU Segre, J Kong, HD Candotti, F Holland, SM Freeman, AF Oh, JL Sokolic, RA AF Segre, Julie Kong, Heidi Candotti, Fabio Holland, Steven M. Freeman, Alexandra F. Oh, Julia Sokolic, Robert A. TI What's the 'Skinny' on Microbiome? Interplay of Immune Cells, Microbes, and Skin Barrier in Health and Disease SO BLOOD LA English DT Meeting Abstract CT 56th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2014 CL San Francisco, CA SP Amer Soc Hematol C1 [Segre, Julie; Candotti, Fabio; Oh, Julia; Sokolic, Robert A.] NHGRI, NIH, Bethesda, MD 20892 USA. [Kong, Heidi] NCI, CCR, NIH, Bethesda, MD 20892 USA. [Holland, Steven M.] NIH, Ctr Clin, Bethesda, MD 20892 USA. [Freeman, Alexandra F.] NIAID, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 4 U2 10 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 2021 L ST NW, SUITE 900, WASHINGTON, DC 20036 USA SN 0006-4971 EI 1528-0020 J9 BLOOD JI Blood PD DEC 6 PY 2014 VL 124 IS 21 PG 3 WC Hematology SC Hematology GA CA9HU UT WOS:000349233800157 ER PT J AU Shirley, CM Chu, SH Yang, YD Wright, GW Staudt, LM Small, D AF Shirley, Courtney M. Chu, S. Haihua Yang, Yandan Wright, George W. Staudt, Louis M. Small, Donald TI Genetic and Pharmacologic Notch4 Inhibition Synergizes with FLT3 Tyrosine Kinase Inhibition in Vitro to More Effectively Eliminate FLT3/ITD-Positive Leukemia Cells SO BLOOD LA English DT Meeting Abstract CT 56th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2014 CL San Francisco, CA SP Amer Soc Hematol C1 [Shirley, Courtney M.; Chu, S. Haihua] Johns Hopkins Univ, Sch Med, Baltimore, MD USA. [Yang, Yandan; Wright, George W.] NCI, Bethesda, MD 20892 USA. [Staudt, Louis M.] NCI, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. [Small, Donald] Johns Hopkins Univ, Sch Med, Baltimore, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 2021 L ST NW, SUITE 900, WASHINGTON, DC 20036 USA SN 0006-4971 EI 1528-0020 J9 BLOOD JI Blood PD DEC 6 PY 2014 VL 124 IS 21 PG 3 WC Hematology SC Hematology GA CA9KX UT WOS:000349243503047 ER PT J AU Siddiqi, T Frankel, P Ruel, C Chen, RW Kelly, KR Tuscano, J Popplewell, L Forman, SJ Piekarz, R Newman, E AF Siddiqi, Tanya Frankel, Paul Ruel, Chris Chen, Robert W. Kelly, Kevin R. Tuscano, Joseph Popplewell, Leslie Forman, Stephen J. Piekarz, Richard Newman, Edward TI Phase 1 Study of MLN8237, an Aurora KinaseA (AURKA) Inhibitor, Combined with Vorinostat, a Histone Deacetylase (HDAC) Inhibitor, in Lymphoid Malignancies SO BLOOD LA English DT Meeting Abstract CT 56th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2014 CL San Francisco, CA SP Amer Soc Hematol C1 [Siddiqi, Tanya; Frankel, Paul; Forman, Stephen J.; Newman, Edward] City Hope Natl Med Ctr, Duarte, CA 91010 USA. [Ruel, Chris; Chen, Robert W.; Popplewell, Leslie] City Hope Natl Med Ctr, Duarte, CA USA. [Kelly, Kevin R.] Univ So Calif, Los Angeles, CA USA. [Tuscano, Joseph] UC Davis Med Ctr, Sacramento, CA USA. [Piekarz, Richard] NCI, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 2 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 2021 L ST NW, SUITE 900, WASHINGTON, DC 20036 USA SN 0006-4971 EI 1528-0020 J9 BLOOD JI Blood PD DEC 6 PY 2014 VL 124 IS 21 PG 3 WC Hematology SC Hematology GA CA9HU UT WOS:000349233806188 ER PT J AU Sokolic, RA Chonat, S Risinger, M Eckhaus, M Garabedian, E Calvo, KR Maric, I Kalfa, TA Candotti, F AF Sokolic, Robert A. Chonat, Satheesh Risinger, Mary Eckhaus, Michael Garabedian, Elizabeth Calvo, Katherine R. Maric, Irina Kalfa, Theodosia A. Candotti, Fabio TI Cation Leak in Red Blood Cells of Patients with Wiskott-Aldrich Syndrome Leads to Non-Immunologic Hemolysis SO BLOOD LA English DT Meeting Abstract CT 56th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2014 CL San Francisco, CA SP Amer Soc Hematol C1 [Sokolic, Robert A.; Eckhaus, Michael; Garabedian, Elizabeth; Calvo, Katherine R.; Maric, Irina] NIH, Bethesda, MD 20892 USA. [Chonat, Satheesh; Risinger, Mary; Kalfa, Theodosia A.] Cincinnati Childrens Hosp Med Ctr, Cincinnati, OH 45229 USA. [Kalfa, Theodosia A.] Univ Cincinnati, Coll Med, Cincinnati, OH USA. [Candotti, Fabio] NHGRI, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 2021 L ST NW, SUITE 900, WASHINGTON, DC 20036 USA SN 0006-4971 EI 1528-0020 J9 BLOOD JI Blood PD DEC 6 PY 2014 VL 124 IS 21 PG 3 WC Hematology SC Hematology GA CA9HU UT WOS:000349233802111 ER PT J AU Spinner, MA Odio, C Calvo, KR Hsu, AP Zerbe, CS Cuellar-Rodriguez, J Ker, JP Stoudenmire, CJ Fadare, O Ghosh, A Mace, EM Orange, JS Hickstein, DD Holland, SM AF Spinner, Michael A. Odio, Camila Calvo, Katherine R. Hsu, Amy P. Zerbe, Christa S. Cuellar-Rodriguez, Jennifer Ker, Jennifer P. Stoudenmire, Charles J. Fadare, Oluwole Ghosh, Arunima Mace, Emily M. Orange, Jordan S. Hickstein, Dennis D. Holland, Steven M. TI Hemophagocytic Lymphohistiocytosis Associated with NK Cell Dysfunction and Disseminated Herpesvirus Infection in GATA2 Deficiency/Monomac Syndrome SO BLOOD LA English DT Meeting Abstract CT 56th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2014 CL San Francisco, CA SP Amer Soc Hematol C1 [Spinner, Michael A.] Stanford Univ, Med Ctr, Stanford, CA 94305 USA. [Odio, Camila] Case Western Reserve Univ, Cleveland Clin, Lerner Coll Med, Cleveland, OH 44106 USA. [Calvo, Katherine R.; Holland, Steven M.] NIH, Bethesda, MD 20892 USA. [Hsu, Amy P.; Zerbe, Christa S.; Cuellar-Rodriguez, Jennifer] NIAID, Bethesda, MD 20892 USA. [Ker, Jennifer P.; Stoudenmire, Charles J.; Fadare, Oluwole] Vanderbilt Univ, Med Ctr, Nashville, TN USA. [Ghosh, Arunima; Hickstein, Dennis D.] NCI, Bethesda, MD 20892 USA. [Mace, Emily M.; Orange, Jordan S.] Texas Childrens Hosp, Baylor Coll Med, Houston, TX 77030 USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 2021 L ST NW, SUITE 900, WASHINGTON, DC 20036 USA SN 0006-4971 EI 1528-0020 J9 BLOOD JI Blood PD DEC 6 PY 2014 VL 124 IS 21 PG 3 WC Hematology SC Hematology GA CA9HU UT WOS:000349233806137 ER PT J AU Tanimoto, K Fujiwara, H Tanaka, H Ochi, F Asai, H Okamoto, S Mineno, J Kuzushima, K Shiku, H Barrett, J Yasukawa, M AF Tanimoto, Kazushi Fujiwara, Hiroshi Tanaka, Hiroki Ochi, Fumihiro Asai, Hiroaki Okamoto, Sachiko Mineno, Junichi Kuzushima, Kiyotaka Shiku, Hiroshi Barrett, John Yasukawa, Masaki TI Concomitant Administration of Gene-Modified T Cells Expressing a Chimeric CD16-CD3 zeta Receptor with Mogamulizmab Synergistically Suppresses Adult T Cell Leukemia Cells in Vivo SO BLOOD LA English DT Meeting Abstract CT 56th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2014 CL San Francisco, CA SP Amer Soc Hematol C1 [Tanimoto, Kazushi; Fujiwara, Hiroshi; Tanaka, Hiroki; Ochi, Fumihiro; Asai, Hiroaki; Yasukawa, Masaki] Ehime Univ, Grad Sch Med, Toon, Japan. [Okamoto, Sachiko; Mineno, Junichi] Takara Bio Inc, Otsu, Shiga, Japan. [Kuzushima, Kiyotaka] Aichi Canc Ctr, Res Inst, Nagoya, Aichi 464, Japan. [Shiku, Hiroshi] Mie Univ, Tsu, Mie 514, Japan. [Barrett, John] NHLBI, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 2021 L ST NW, SUITE 900, WASHINGTON, DC 20036 USA SN 0006-4971 EI 1528-0020 J9 BLOOD JI Blood PD DEC 6 PY 2014 VL 124 IS 21 PG 3 WC Hematology SC Hematology GA CA9KX UT WOS:000349243504134 ER PT J AU Thordardottir, M Lund, SH Lindqvist, EK Costello, R Burton, D Korde, N Mailankody, S Eiriksdottir, G Launer, LJ Gudnason, V Harris, TB Landgren, O Kristinsson, SY AF Thordardottir, Marianna Lund, Sigrun Helga Lindqvist, Ebba K. Costello, Rene Burton, Debra Korde, Neha Mailankody, Sham Eiriksdottir, Gudny Launer, Lenore J. Gudnason, Vilmundur Harris, Tamara B. Landgren, Ola Kristinsson, Sigurdur Y. TI Obesity and Risk of Monoclonal Gammopathy of Undetermined Significance: A Population-Based Study SO BLOOD LA English DT Meeting Abstract CT 56th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2014 CL San Francisco, CA SP Amer Soc Hematol C1 [Thordardottir, Marianna; Lund, Sigrun Helga; Gudnason, Vilmundur; Kristinsson, Sigurdur Y.] Univ Iceland, Reykjavik, Iceland. [Lindqvist, Ebba K.; Landgren, Ola; Kristinsson, Sigurdur Y.] Karolinska Univ Hosp, Stockholm, Sweden. [Lindqvist, Ebba K.; Landgren, Ola; Kristinsson, Sigurdur Y.] Karolinska Inst, Stockholm, Sweden. [Costello, Rene; Burton, Debra; Mailankody, Sham] NCI, NIH, Bethesda, MD 20892 USA. [Korde, Neha; Landgren, Ola] Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. [Eiriksdottir, Gudny; Gudnason, Vilmundur] Iceland Heart Assoc, Kopavogur, Iceland. [Launer, Lenore J.; Harris, Tamara B.] NIH, Bethesda, MD 20892 USA. RI Gudnason, Vilmundur/K-6885-2015; Kristinsson, Sigurdur /M-2910-2015 OI Gudnason, Vilmundur/0000-0001-5696-0084; Kristinsson, Sigurdur /0000-0002-4964-7476 NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 2021 L ST NW, SUITE 900, WASHINGTON, DC 20036 USA SN 0006-4971 EI 1528-0020 J9 BLOOD JI Blood PD DEC 6 PY 2014 VL 124 IS 21 PG 3 WC Hematology SC Hematology GA CA9HU UT WOS:000349233803153 ER PT J AU Uchida, N Fujita, A Winkler, T Tisdale, JF AF Uchida, Naoya Fujita, Atsushi Winkler, Thomas Tisdale, John F. TI beta- Globin-Expressing Definitive Erythroid Progenitor Cells Generated from Embryonic and Induced Pluripotent Stem Cell-Derived Sacs SO BLOOD LA English DT Meeting Abstract CT 56th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2014 CL San Francisco, CA SP Amer Soc Hematol C1 [Uchida, Naoya; Fujita, Atsushi; Tisdale, John F.] NHLBI, NIDDK, NIH, Bethesda, MD 20892 USA. [Winkler, Thomas] NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 2021 L ST NW, SUITE 900, WASHINGTON, DC 20036 USA SN 0006-4971 EI 1528-0020 J9 BLOOD JI Blood PD DEC 6 PY 2014 VL 124 IS 21 PG 3 WC Hematology SC Hematology GA CA9KX UT WOS:000349243508020 ER PT J AU Vitrano, A Calvaruso, G Di Maggio, R Sacco, M Quota, A Capra, M Filosa, A D'Ascola, DG Fidone, C Carollo, A Pitrolo, L Gerardi, C Colletti, G Roccamo, G Romeo, MA Cianciulli, P Lai, ME Rigoli, LC Forni, G Maggio, A AF Vitrano, Angela Calvaruso, Giuseppina Di Maggio, Rosario Sacco, Massimiliano Quota, Alessandra Capra, Marcello Filosa, Aldo D'Ascola, Domenico Giuseppe Fidone, Carmelo Carollo, Antonella Pitrolo, Lorella Gerardi, Calogera Colletti, Grazia Roccamo, Gaetano Romeo, Maria Antonietta Cianciulli, Paolo Lai, Maria-Eliana Rigoli, Luciana Concetta Forni, Gianluca Maggio, Aurelio TI Deferiprone Versus Deferoxamine in Thalassemia Intermedia: Results from 5-Year Long-Term Italian Multi-Center Randomized Clinical Trial SO BLOOD LA English DT Meeting Abstract CT 56th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2014 CL San Francisco, CA SP Amer Soc Hematol C1 [Vitrano, Angela; Calvaruso, Giuseppina; Sacco, Massimiliano; Pitrolo, Lorella; Maggio, Aurelio] AOR Villa Sofia V Cervello, Palermo, Italy. [Di Maggio, Rosario] NIDDK, NHLBI, NIH, Bethesda, MD 20892 USA. [Quota, Alessandra] AOV Emanuele III, Gela, CL, Italy. [Capra, Marcello] PO Osped Civ & Benfratelli, Palermo, Italy. [Filosa, Aldo] AORNA Cardarelli, Naples, Italy. [D'Ascola, Domenico Giuseppe] AO Bianchi Melacrino Morelli, Reggio Di Calabria, Italy. [Fidone, Carmelo] AOM Paterno Arezzo, Ragusa, Italy. [Carollo, Antonella] Az Osp, Trapani, Italy. [Gerardi, Calogera] AOOCR, Sciacca, Italy. [Colletti, Grazia] Univ Ferrara, I-44100 Ferrara, Italy. [Roccamo, Gaetano] Presidio Osped S Agata Militello ASP ME, S Agata Di Militello, Italy. [Romeo, Maria Antonietta] Azienda Policlin, Catania, Italy. [Cianciulli, Paolo] Osped Rome, Rome, Italy. [Lai, Maria-Eliana] Univ Cagliari, Sch Med, Cagliari, Italy. [Rigoli, Luciana Concetta] Policlin G Martino, Messina, Italy. [Forni, Gianluca] Osped Galliera, Genoa, Italy. NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 2021 L ST NW, SUITE 900, WASHINGTON, DC 20036 USA SN 0006-4971 EI 1528-0020 J9 BLOOD JI Blood PD DEC 6 PY 2014 VL 124 IS 21 PG 4 WC Hematology SC Hematology GA CA9HU UT WOS:000349233802177 ER PT J AU Wang, C Iqbal, J Zhang, WW McKeithan, T Rosenwald, A Gascoyne, RD Steidl, C Bouska, A Muhammad, Z Jiang, B Rohr, J Cannon, A Fu, K Weisenburger, DD Greiner, TC Smith, LM Dybkaer, K Ott, G Nakamura, S Seto, M Berger, F Rogan, EG Staudt, LM Vose, JM Chan, WC AF Wang, Chao Iqbal, Javeed Zhang, Weiwei McKeithan, Timothy Rosenwald, Andreas Gascoyne, Randy D. Steidl, Christian Bouska, Alyssa Muhammad, Zahid Jiang, Bei Rohr, Joseph Cannon, Andrew Fu, Kai Weisenburger, Dennis D. Greiner, Timothy C. Smith, Lynette M. Dybkaer, Karen Ott, German Nakamura, Shigeo Seto, Masao Berger, Francoise Rogan, Eleanor G. Staudt, Louis M. Vose, Julie M. Chan, Wing Chung TI IDH2(R172) Mutations Define a Unique Subgroup of Patients in Angioimmunoblastic T-Cell Lymphoma SO BLOOD LA English DT Meeting Abstract CT 56th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2014 CL San Francisco, CA SP Amer Soc Hematol C1 [Wang, Chao; Iqbal, Javeed; Zhang, Weiwei; Bouska, Alyssa; Muhammad, Zahid; Jiang, Bei; Rohr, Joseph; Cannon, Andrew; Fu, Kai; Greiner, Timothy C.; Smith, Lynette M.; Rogan, Eleanor G.; Vose, Julie M.] Univ Nebraska Med Ctr, Omaha, NE USA. [Wang, Chao] Shandong Univ, Jinan 250100, Peoples R China. [McKeithan, Timothy; Weisenburger, Dennis D.; Chan, Wing Chung] City Hope Natl Med Ctr, Duarte, CA 91010 USA. [Rosenwald, Andreas] Univ Wurzburg, D-97070 Wurzburg, Germany. [Gascoyne, Randy D.; Steidl, Christian] British Columbia Canc Agcy, Vancouver, BC V5Z 4E6, Canada. [Dybkaer, Karen] Aalborg Univ Hosp, Aalborg, Denmark. [Ott, German] Robert Bosch Krankenhaus, Stuttgart, Germany. [Ott, German] Dr Margarete Fischer Bosch Inst Clin Pharmacol, Stuttgart, Germany. [Nakamura, Shigeo] Nagoya Univ, Grad Sch Med, Nagoya, Aichi 4648601, Japan. [Seto, Masao] Aichi Canc Ctr, Res Inst, Nagoya, Aichi 464, Japan. [Berger, Francoise] Univ Lyon 1, Dept Pathol & Hematol, Hosp Civils Lyon, F-69365 Lyon, France. [Staudt, Louis M.] NCI, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 1 U2 3 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 2021 L ST NW, SUITE 900, WASHINGTON, DC 20036 USA SN 0006-4971 EI 1528-0020 J9 BLOOD JI Blood PD DEC 6 PY 2014 VL 124 IS 21 PG 3 WC Hematology SC Hematology GA CA9HU UT WOS:000349233807103 ER PT J AU Williams, KM Chakrabarty, JLH Lindenberg, L Adler, S Gea-Banacloche, J Blacklock-Schuver, B Hakim, FT Hickstein, DD Kochenderfer, JN Wilder, J Chinn, T Kurdziel, K Steinberg, SM Khuu, H Lin, FI Fowler, DH Halverson, D Avila, DN Selby, G Taylor, TN Mann, J Hsu, J Epstein, RB Anderson, SL Chuong, N Havlicek, J Li, SB Pham, T Kraus, T Vesely, SK Pavletic, SZ Bollard, CM Choyke, P Gress, RE AF Williams, Kirsten M. Chakrabarty, Jennifer L. Holter Lindenberg, Liza Adler, Steve Gea-Banacloche, Juan Blacklock-Schuver, Bazetta Hakim, Frances T. Hickstein, Dennis D. Kochenderfer, James N. Wilder, Jennifer Chinn, Tracey Kurdziel, Karen Steinberg, Seth M. Khuu, Hanh Lin, Frank I. Fowler, Daniel H. Halverson, David Avila, Daniele N. Selby, George Taylor, Tiffani N. Mann, Jennifer Hsu, Jennifer Epstein, Robert B. Anderson, Stacy L. Nguyen Chuong Havlicek, Joseph Li, Shibo Tom Pham Kraus, Teresa Vesely, Sara K. Pavletic, Steven Z. Bollard, Catherine M. Choyke, Peter Gress, Ronald E. TI FLT Imaging Reveals Kinetics and Biology of Engraftment after Myeloablative HSCT SO BLOOD LA English DT Meeting Abstract CT 56th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2014 CL San Francisco, CA SP Amer Soc Hematol C1 [Williams, Kirsten M.; Lindenberg, Liza; Adler, Steve; Blacklock-Schuver, Bazetta; Wilder, Jennifer; Kurdziel, Karen; Khuu, Hanh; Lin, Frank I.; Mann, Jennifer] NIH, Bethesda, MD 20892 USA. [Williams, Kirsten M.; Bollard, Catherine M.] Childrens Natl Med Ctr, Washington, DC 20010 USA. [Chakrabarty, Jennifer L. Holter; Selby, George; Epstein, Robert B.; Anderson, Stacy L.; Li, Shibo; Tom Pham; Kraus, Teresa; Vesely, Sara K.] Univ Oklahoma, Hlth Sci Ctr, Oklahoma City, OK USA. [Gea-Banacloche, Juan; Hakim, Frances T.; Hickstein, Dennis D.; Kochenderfer, James N.; Steinberg, Seth M.; Fowler, Daniel H.; Halverson, David; Pavletic, Steven Z.] NCI, Bethesda, MD 20892 USA. [Chinn, Tracey; Avila, Daniele N.; Taylor, Tiffani N.; Hsu, Jennifer; Choyke, Peter; Gress, Ronald E.] NCI, NIH, Bethesda, MD 20892 USA. [Nguyen Chuong; Havlicek, Joseph] Univ Oklahoma, Norman, OK 73019 USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 2021 L ST NW, SUITE 900, WASHINGTON, DC 20036 USA SN 0006-4971 EI 1528-0020 J9 BLOOD JI Blood PD DEC 6 PY 2014 VL 124 IS 21 PG 3 WC Hematology SC Hematology GA CA9HU UT WOS:000349233808112 ER PT J AU Yang, JJ Xu, H Bhojwani, D Moriyama, T Qian, MX Yang, X Seibel, NL Relling, MV Carroll, WL Pui, CH Evans, WE AF Yang, Jun J. Xu, Heng Bhojwani, Deepa Moriyama, Takaya Qian, Maoxiang Yang, Xue Seibel, Nita L. Relling, Mary V. Carroll, William L. Pui, Ching-Hon Evans, William E. TI ARID5B Regulates Leukemia Sensitivity to Antimetabolites in Children with Acute Lymphoblastic Leukemia Via Effects on Cell Cycle Progression SO BLOOD LA English DT Meeting Abstract CT 56th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2014 CL San Francisco, CA SP Amer Soc Hematol C1 [Yang, Jun J.; Xu, Heng; Bhojwani, Deepa; Moriyama, Takaya; Qian, Maoxiang; Yang, Xue; Relling, Mary V.; Pui, Ching-Hon; Evans, William E.] St Jude Childrens Res Hosp, Memphis, TN 38105 USA. [Yang, Xue] Univ Tennessee, Ctr Hlth Sci, Memphis, TN 38163 USA. [Seibel, Nita L.] NCI, Bethesda, MD 20892 USA. [Carroll, William L.] NYU, Inst Canc, New York, NY USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 2021 L ST NW, SUITE 900, WASHINGTON, DC 20036 USA SN 0006-4971 EI 1528-0020 J9 BLOOD JI Blood PD DEC 6 PY 2014 VL 124 IS 21 PG 3 WC Hematology SC Hematology GA CA9HU UT WOS:000349233807141 ER PT J AU Yang, YM Chien, CD Jacoby, E Qin, HY Haso, W Fry, TJ AF Yang, Yinmeng Chien, Christopher Daniel Jacoby, Elad Qin, Haiying Haso, Waleed Fry, Terry J. TI Presence of Endogenous TCR Antigen in Vivo Attenuates Efficacy of Anti-CD19 Targeted CAR T Cell Therapy SO BLOOD LA English DT Meeting Abstract CT 56th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2014 CL San Francisco, CA SP Amer Soc Hematol C1 [Yang, Yinmeng; Chien, Christopher Daniel; Jacoby, Elad; Qin, Haiying; Fry, Terry J.] NCI, NIH, Bethesda, MD 20892 USA. [Yang, Yinmeng] Georgetown Univ, Washington, DC USA. [Haso, Waleed] NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 2021 L ST NW, SUITE 900, WASHINGTON, DC 20036 USA SN 0006-4971 EI 1528-0020 J9 BLOOD JI Blood PD DEC 6 PY 2014 VL 124 IS 21 PG 3 WC Hematology SC Hematology GA CA9HU UT WOS:000349233801026 ER PT J AU Yoshizato, T Dumitriu, B Hosokawa, K Makishima, H Yoshida, K Sato, A Okuno, Y Kataoka, K Chiba, K Tanaka, H Shiraishi, Y Nagata, Y Suzuki, H Sato, Y Shiozawa, Y Katagiri, T Kon, A Clemente, M Sanada, M Miyano, S Maciejewski, JP Nakao, S Young, NS Ogawa, S AF Yoshizato, Tetsuichi Dumitriu, Bogdan Hosokawa, Kohei Makishima, Hideki Yoshida, Kenichi Sato, Aiko Okuno, Yusuke Kataoka, Keisuke Chiba, Kenichi Tanaka, Hiroko Shiraishi, Yuichi Nagata, Yasunobu Suzuki, Hiromichi Sato, Yusuke Shiozawa, Yusuke Katagiri, Takamasa Kon, Ayana Clemente, Michael Sanada, Masashi Miyano, Satoru Maciejewski, Jaroslaw P. Nakao, Shinji Young, Neal S. Ogawa, Seishi TI Chronological Analysis of Clonal Evolution in Acquired Aplastic Anemia SO BLOOD LA English DT Meeting Abstract CT 56th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2014 CL San Francisco, CA SP Amer Soc Hematol C1 [Yoshizato, Tetsuichi; Yoshida, Kenichi; Sato, Aiko; Kataoka, Keisuke; Nagata, Yasunobu; Suzuki, Hiromichi; Sato, Yusuke; Shiozawa, Yusuke; Kon, Ayana; Sanada, Masashi; Ogawa, Seishi] Kyoto Univ, Grad Sch Med, Kyoto, Japan. [Dumitriu, Bogdan; Young, Neal S.] NHLBI, NIH, Bethesda, MD 20892 USA. [Hosokawa, Kohei; Katagiri, Takamasa; Nakao, Shinji] Kanazawa Univ, Grad Sch Med Sci, Kanazawa, Ishikawa, Japan. [Makishima, Hideki; Clemente, Michael; Maciejewski, Jaroslaw P.] Cleveland Clin, Cleveland, OH 44106 USA. [Okuno, Yusuke] Nagoya Univ, Grad Sch Med, Nagoya, Aichi 4648601, Japan. [Chiba, Kenichi; Tanaka, Hiroko; Shiraishi, Yuichi; Miyano, Satoru] Univ Tokyo, Inst Med Sci, Tokyo, Japan. NR 0 TC 0 Z9 0 U1 1 U2 1 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 2021 L ST NW, SUITE 900, WASHINGTON, DC 20036 USA SN 0006-4971 EI 1528-0020 J9 BLOOD JI Blood PD DEC 6 PY 2014 VL 124 IS 21 PG 4 WC Hematology SC Hematology GA CA9HU UT WOS:000349233800097 ER PT J AU Young, NS Dumitriu, B Ogawa, S AF Young, Neal S. Dumitriu, Bogdan Ogawa, Seishi TI Acquired Aplastic Anemia: New Genetics, New Genomics SO BLOOD LA English DT Meeting Abstract CT 56th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2014 CL San Francisco, CA SP Amer Soc Hematol C1 [Young, Neal S.] NIH, Bethesda, MD 20892 USA. [Dumitriu, Bogdan] NHLBI, NIH, Bethesda, MD 20892 USA. [Ogawa, Seishi] Kyoto Univ, Grad Sch Med, Kyoto, Japan. NR 0 TC 0 Z9 0 U1 0 U2 2 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 2021 L ST NW, SUITE 900, WASHINGTON, DC 20036 USA SN 0006-4971 EI 1528-0020 J9 BLOOD JI Blood PD DEC 6 PY 2014 VL 124 IS 21 PG 2 WC Hematology SC Hematology GA CA9KX UT WOS:000349243501124 ER PT J AU Zanin-Zhorov, A Flynn, R Luznik, L Panoskaltsis-Mortari, A Jing, D Goodman, K Weiss, J Nyuydzefe, M Chen, W Serody, JS MacDonald, KPA Hill, GR O'Shea, J Roche, M Weiss, S Waksal, S Blazar, BR AF Zanin-Zhorov, Alexandra Flynn, Ryan Luznik, Leo Panoskaltsis-Mortari, Angela Jing, Du Goodman, Katelyn Weiss, Jonathan Nyuydzefe, Melanie Chen, Wei Serody, Jonathan S. MacDonald, Kelli P. A. Hill, Geoffrey R. O'Shea, John Roche, Maria Weiss, Sara Waksal, Samuel Blazar, Bruce R. TI A Selective and Potent Rock 2 Inhibitor (KD025) Decreases Human STAT3-Dependent IL-21 and IL-17 Production and Experimental Chronic Graft-Versus-Host Disease (cGVHD) SO BLOOD LA English DT Meeting Abstract CT 56th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2014 CL San Francisco, CA SP Amer Soc Hematol C1 [Zanin-Zhorov, Alexandra; Weiss, Jonathan; Nyuydzefe, Melanie; Chen, Wei] Kadmon Res Inst, New York, NY USA. [Flynn, Ryan] Masonic Canc Ctr, Minneapolis, MN USA. [Flynn, Ryan] Dept Pediatircs, Minneapolis, MN USA. [Luznik, Leo] Johns Hopkins Univ, Sch Med, Baltimore, MD USA. [Panoskaltsis-Mortari, Angela; Jing, Du; Goodman, Katelyn; Blazar, Bruce R.] Univ Minnesota, Minneapolis, MN USA. [Serody, Jonathan S.] Univ N Carolina, Lineberger Comprehens Canc Ctr, Chapel Hill, NC 27599 USA. [MacDonald, Kelli P. A.; Hill, Geoffrey R.] Queensland Inst Med Res, Brisbane, Qld 4006, Australia. [O'Shea, John] NIH, Bethesda, MD 20892 USA. [Roche, Maria; Weiss, Sara; Waksal, Samuel] Kadmon, New York, NY USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 2021 L ST NW, SUITE 900, WASHINGTON, DC 20036 USA SN 0006-4971 EI 1528-0020 J9 BLOOD JI Blood PD DEC 6 PY 2014 VL 124 IS 21 PG 3 WC Hematology SC Hematology GA CA9KX UT WOS:000349243506117 ER PT J AU Zeidner, JF Karp, JE Blackford, A Mejias, J Smith, G Ivy, SP Harris, P AF Zeidner, Joshua F. Karp, Judith E. Blackford, Amanda Mejias, Jose Smith, Gary Ivy, S. Percy Harris, Pamela TI A Comprehensive Assessment of Phase 1 Clinical Trials in Acute Myeloid Leukemia SO BLOOD LA English DT Meeting Abstract CT 56th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2014 CL San Francisco, CA SP Amer Soc Hematol C1 [Zeidner, Joshua F.] Univ N Carolina, Lineberger Comprehens Canc Ctr, Chapel Hill, NC 27599 USA. [Karp, Judith E.] Sidney Kimmel Comprehens Canc Ctr John Hopkins, Baltimore, MD USA. [Blackford, Amanda] Johns Hopkins Univ Hosp, Sidney Kimmel Comprehens Canc Ctr, Baltimore, MD 21287 USA. [Mejias, Jose] Theradex Syst Inc, CTMS, Rockville, MD USA. [Smith, Gary; Ivy, S. Percy; Harris, Pamela] NCI, Rockville, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 2021 L ST NW, SUITE 900, WASHINGTON, DC 20036 USA SN 0006-4971 EI 1528-0020 J9 BLOOD JI Blood PD DEC 6 PY 2014 VL 124 IS 21 PG 3 WC Hematology SC Hematology GA CA9KX UT WOS:000349243501037 ER PT J AU Zerbe, CS Cuellar-Rodriguez, J Gea-Banacloche, J Holland, SM Hickstein, DD AF Zerbe, Christa S. Cuellar-Rodriguez, Jennifer Gea-Banacloche, Juan Holland, Steven M. Hickstein, Dennis D. TI Successful Haploidentical Hematopoietic Stem Cell Transplant for GATA2 Deficiency SO BLOOD LA English DT Meeting Abstract CT 56th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2014 CL San Francisco, CA SP Amer Soc Hematol C1 [Zerbe, Christa S.] NIAID, Bethesda, MD 20892 USA. [Cuellar-Rodriguez, Jennifer] Natl Inst Med Sci & Nutr Salvador Zubiran, Mexico City, DF, Mexico. [Gea-Banacloche, Juan; Hickstein, Dennis D.] NCI, Bethesda, MD 20892 USA. [Holland, Steven M.] NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 2021 L ST NW, SUITE 900, WASHINGTON, DC 20036 USA SN 0006-4971 EI 1528-0020 J9 BLOOD JI Blood PD DEC 6 PY 2014 VL 124 IS 21 PG 3 WC Hematology SC Hematology GA CA9HU UT WOS:000349233808061 ER PT J AU Zhao, L Alemu, L Cheng, J Zhen, T Friedman, AD Liu, PP AF Zhao, Ling Alemu, Lemlem Cheng, Jun Zhen, Tao Friedman, Alan D. Liu, Pu Paul TI Functional Dissection of the C Terminus of CBF beta-SMMHC Indicates a Critical Role of the Multimerization Domain during Hematopoiesis and Leukemogenesis SO BLOOD LA English DT Meeting Abstract CT 56th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2014 CL San Francisco, CA SP Amer Soc Hematol C1 [Zhao, Ling; Alemu, Lemlem; Cheng, Jun; Zhen, Tao; Liu, Pu Paul] NIH, Bethesda, MD 20892 USA. [Friedman, Alan D.] Johns Hopkins Univ, Sch Med, Baltimore, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 2021 L ST NW, SUITE 900, WASHINGTON, DC 20036 USA SN 0006-4971 EI 1528-0020 J9 BLOOD JI Blood PD DEC 6 PY 2014 VL 124 IS 21 PG 3 WC Hematology SC Hematology GA CA9KX UT WOS:000349243507059 ER PT J AU Chang, LJ Dowd, KA Mendoza, FH Saunders, JG Sitar, S Plummer, SH Yamshchikov, G Sarwar, UN Hu, ZH Enama, ME Bailer, RT Koup, RA Schwartz, RM Akahata, W Nabel, GJ Mascola, JR Pierson, TC Graham, BS Ledgerwood, JE AF Chang, Lee-Jah Dowd, Kimberly A. Mendoza, Floreliz H. Saunders, Jamie G. Sitar, Sandra Plummer, Sarah H. Yamshchikov, Galina Sarwar, Uzma N. Hu, Zonghui Enama, Mary E. Bailer, Robert T. Koup, Richard A. Schwartz, Richard M. Akahata, Wataru Nabel, Gary J. Mascola, John R. Pierson, Theodore C. Graham, Barney S. Ledgerwood, Julie E. CA VRC 311 Study Team TI Safety and tolerability of chikungunya virus-like particle vaccine in healthy adults: a phase 1 dose-escalation trial SO LANCET LA English DT Article ID PROTECTS MICE; INFECTION; EPIDEMIC; DISEASE; IMMUNOGENICITY; CANDIDATES; EMERGENCE AB Background Chikungunya virus-a mosquito-borne alphavirus-is endemic in Africa and south and southeast Asia and has recently emerged in the Caribbean. No drugs or vaccines are available for treatment or prevention. We aimed to assess the safety, tolerability, and immunogenicity of a new candidate vaccine. Methods VRC 311 was a phase 1, dose-escalation, open-label clinical trial of a virus-like particle (VLP) chikungunya virus vaccine, VRC-CHKVLP059-00-VP, in healthy adults aged 18-50 years who were enrolled at the National Institutes of Health Clinical Center (Bethesda, MD, USA). Participants were assigned to sequential dose level groups to receive vaccinations at 10 mu g, 20 mu g, or 40 mu g on weeks 0, 4, and 20, with follow-up for 44 weeks after enrolment. The primary endpoints were safety and tolerability of the vaccine. Secondary endpoints were chikungunya virus-specific immune responses assessed by ELISA and neutralising antibody assays. This trial is registered with ClinicalTrials.gov, NCT01489358. Findings 25 participants were enrolled from Dec 12, 2011, to March 22, 2012, into the three dosage groups: 10 mu g (n=5), 20 mu g (n=10), and 40 mu g (n=10). The protocol was completed by all five participants at the 10 mu g dose, all ten participants at the 20 mu g dose, and eight of ten participants at the 40 mu g dose; non-completions were for personal circumstances unrelated to adverse events. 73 vaccinations were administered. All injections were well tolerated, with no serious adverse events reported. Neutralising antibodies were detected in all dose groups after the second vaccination (geometric mean titres of the half maximum inhibitory concentration: 2688 in the 10 mu g group, 1775 in the 20 mu g group, and 7246 in the 40 mu g group), and a significant boost occurred after the third vaccination in all dose groups (10 mu g group p = 0.0197, 20 mu g group p < 0.0001, and 40 mu g group p < 0.0001). 4 weeks after the third vaccination, the geometric mean titres of the half maximum inhibitory concentration were 8745 for the 10 mu g group, 4525 for the 20 mu g group, and 5390 for the 40 mu g group. Interpretation The chikungunya VLP vaccine was immunogenic, safe, and well tolerated. This study represents an important step in vaccine development to combat this rapidly emerging pathogen. Further studies should be done in a larger number of participants and in more diverse populations. C1 [Chang, Lee-Jah; Mendoza, Floreliz H.; Saunders, Jamie G.; Sitar, Sandra; Plummer, Sarah H.; Yamshchikov, Galina; Sarwar, Uzma N.; Enama, Mary E.; Bailer, Robert T.; Koup, Richard A.; Schwartz, Richard M.; Akahata, Wataru; Nabel, Gary J.; Mascola, John R.; Graham, Barney S.; Ledgerwood, Julie E.] NIAID, Vaccine Res Ctr, NIH, Bethesda, MD 20892 USA. [Dowd, Kimberly A.; Pierson, Theodore C.] NIAID, Viral Pathogenesis Sect, Viral Dis Lab, NIH, Bethesda, MD 20892 USA. [Hu, Zonghui] NIAID, Biostat Res Branch, Div Clin Res, NIH, Bethesda, MD 20892 USA. RP Ledgerwood, JE (reprint author), NIAID, Vaccine Res Ctr, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA. EM ledgerwood@mail.nih.gov FU Intramural Research Program of the Vaccine Research Center; National Institutes of Health; National Institute of Allergy and Infectious Diseases FX Intramural Research Program of the Vaccine Research Center, National Institute of Allergy and Infectious Diseases, and National Institutes of Health. NR 46 TC 47 Z9 48 U1 0 U2 20 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0140-6736 EI 1474-547X J9 LANCET JI Lancet PD DEC 6 PY 2014 VL 384 IS 9959 BP 2046 EP 2052 DI 10.1016/S0140-6736(14)61185-5 PG 7 WC Medicine, General & Internal SC General & Internal Medicine GA AW6BD UT WOS:000346353600026 PM 25132507 ER PT J AU Reperant, LA Kuiken, T Grenfell, BT Osterhaus, ADME AF Reperant, Leslie A. Kuiken, Thijs Grenfell, Bryan T. Osterhaus, Albert D. M. E. TI The immune response and within-host emergence of pandemic influenza virus SO LANCET LA English DT Article ID DIVERSE MALARIA INFECTIONS; RESPIRATORY DROPLET; TRANSMISSION; HUMANS; COMPETITION; DYNAMICS; FERRETS AB Zoonotic influenza viruses that are a few mutations away from pandemic viruses circulate in animals, and can evolve into airborne-transmissible viruses in human beings. Paradoxically, such viruses only occasionally emerge in people; the four influenza pandemics that occurred in the past 100 years were caused by zoonotic viruses that acquired efficient transmissibility. Emergence of a pandemic virus in people can happen when transmissible viruses evolve in individuals with zoonotic influenza and replicate to titres allowing transmission. We postulate that this step in the genesis of a pandemic virus only occasionally occurs in human beings, because the immune response triggered by zoonotic influenza virus also controls transmissible mutants that emerge during infection. Therefore, an impaired immune response might be needed for within-host emergence of a pandemic virus and replication to titres allowing transmission. Immunocompromised individuals-eg, those with comorbidities, of advanced age, or receiving immunosuppressive treatment-could be at increased risk of generating transmissible viruses and initiating chains of human-to-human infection. C1 [Reperant, Leslie A.; Kuiken, Thijs; Osterhaus, Albert D. M. E.] Erasmus MC, Dept Virosci, NL-3000 CA Rotterdam, Netherlands. [Reperant, Leslie A.; Osterhaus, Albert D. M. E.] Artemis Res Inst One Hlth Europe, Utrecht, Netherlands. [Grenfell, Bryan T.] Princeton Univ, Dept Ecol & Evolutionary Biol, Princeton, NJ 08544 USA. [Grenfell, Bryan T.] NIH, Fogarty Int Ctr, Bethesda, MD 20892 USA. RP Reperant, LA (reprint author), Erasmus MC, Dept Virosci, POB 2040, NL-3000 CA Rotterdam, Netherlands. EM l.reperant@erasmusmc.nl OI Reperant, Leslie/0000-0002-7212-1595 FU EU [302060, 278976, 223498]; RAPIDD program of the Science and Technology Directorate, Department of Homeland Security; Fogarty International Center, NIH, Department of Homeland Security contract [HSHQDC-12-C-00058]; Bill & Melinda Gates Foundation FX We thank Guus Rimmelzwaan (Department of Viroscience, Erasmus Medical Centre, Netherlands), and Derek Smith and Judy Fonville (Department of Zoology, University of Cambridge, UK) for productive discussions. LAR was supported by EU FP7 Marie-Curie International Incoming Fellowship #302060; TK by EU FP7 ANTIGONE project #278976; BTG by the RAPIDD program of the Science and Technology Directorate, Department of Homeland Security, and the Fogarty International Center, NIH, Department of Homeland Security contract HSHQDC-12-C-00058, and the Bill & Melinda Gates Foundation; and ADMEO by EU FP7 EMPERIE project #223498 and EU FP7 ANTIGONE project #278976. The sponsor of the study had no role in study design, data collection, data analysis, data interpretation, or writing of the report. The corresponding author had full access to all the data in the study and had final responsibility for the decision to submit for publication. NR 22 TC 7 Z9 7 U1 3 U2 20 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0140-6736 EI 1474-547X J9 LANCET JI Lancet PD DEC 6 PY 2014 VL 384 IS 9959 BP 2077 EP 2081 DI 10.1016/S0140-6736(13)62425-3 PG 5 WC Medicine, General & Internal SC General & Internal Medicine GA AW6BD UT WOS:000346353600029 PM 24767965 ER PT J AU Pica, S Sado, DM Maestrini, V Fontana, M White, SK Treibel, T Captur, G Anderson, S Piechnik, SK Robson, MD Lachmann, RH Murphy, E Mehta, A Hughes, D Kellman, P Elliott, PM Herrey, AS Moon, JC AF Pica, Silvia Sado, Daniel M. Maestrini, Viviana Fontana, Marianna White, Steven K. Treibel, Thomas Captur, Gabriella Anderson, Sarah Piechnik, Stefan K. Robson, Matthew D. Lachmann, Robin H. Murphy, Elaine Mehta, Atul Hughes, Derralyn Kellman, Peter Elliott, Perry M. Herrey, Anna S. Moon, James C. TI Reproducibility of native myocardial T1 mapping in the assessment of Fabry disease and its role in early detection of cardiac involvement by cardiovascular magnetic resonance SO JOURNAL OF CARDIOVASCULAR MAGNETIC RESONANCE LA English DT Article DE Cardiovascular magnetic resonance; T1 mapping; Speckle-tracking strain; Diastolic function; Fabry disease ID ENZYME REPLACEMENT THERAPY; 2-DIMENSIONAL STRAIN; DIASTOLIC FUNCTION; OUTCOME SURVEY; CARDIOMYOPATHY; QUANTIFICATION; MOLLI; CMR; HYPERTROPHY; DIAGNOSIS AB Background: Cardiovascular magnetic resonance (CMR) derived native myocardial T1 is decreased in patients with Fabry disease even before left ventricular hypertrophy (LVH) occurs and may be the first non-invasive measure of myocyte sphingolipid storage. The relationship of native T1 lowering prior to hypertrophy and other candidate early phenotype markers are unknown. Furthermore, the reproducibility of T1 mapping has never been assessed in Fabry disease. Methods: Sixty-three patients, 34 (54%) female, mean age 48 +/- 15 years with confirmed (genotyped) Fabry disease underwent CMR, ECG and echocardiographic assessment. LVH was absent in 25 (40%) patients. Native T1 mapping was performed with both Modified Look-Locker Inversion recovery (MOLLI) sequences and a shortened version (ShMOLLI) at 1.5 Tesla. Twenty-one patients underwent a second scan within 24 hours to assess inter-study reproducibility. Results were compared with 63 healthy age and gender-matched volunteers. Results: Mean native T1 in Fabry disease (LVH positive), (LVH negative) and healthy volunteers was 853 +/- 50 ms, 904 +/- 46 ms and 968 +/- 32 ms (for all p < 0.0001) by ShMOLLI sequences. Native T1 showed high inter-study, intra-observer and inter-observer agreement with intra-class correlation coefficients (ICC) of 0.99, 0.98, 0.97 (ShMOLLI) and 0.98, 0.98, 0.98 (MOLLI). In Fabry disease LVH negative individuals, low native T1 was associated with reduced echocardiographic-based global longitudinal speckle tracking strain (-18 +/- 2% vs -22 +/- 2%, p = 0.001) and early diastolic function impairment (E/E' = 7 [6-8] vs 5 [5-6], p = 0.028). Conclusion: Native T1 mapping in Fabry disease is a reproducible technique. T1 reduction prior to the onset of LVH is associated with early diastolic and systolic changes measured by echocardiography. C1 [Pica, Silvia; Sado, Daniel M.; Maestrini, Viviana; Fontana, Marianna; White, Steven K.; Treibel, Thomas; Captur, Gabriella; Anderson, Sarah; Piechnik, Stefan K.; Robson, Matthew D.; Elliott, Perry M.; Herrey, Anna S.; Moon, James C.] Heart Hosp, London W1G 8PH, England. [Pica, Silvia] IRCCS Policlin San Matteo Hosp, Dept Cardiol, Pavia, Italy. [Sado, Daniel M.; White, Steven K.; Treibel, Thomas; Captur, Gabriella; Elliott, Perry M.; Herrey, Anna S.; Moon, James C.] UCL, Inst Cardiovasc Sci, London WC1E 6BT, England. [Maestrini, Viviana] Univ Roma La Sapienza, Dept Cardiovasc Resp Nephrol Anaesthesiol & Geria, I-00185 Rome, Italy. [Piechnik, Stefan K.; Robson, Matthew D.] Univ Oxford, Dept Cardiovasc Med, Oxford Ctr Clin Magnet Resonance Res, Oxford OX3 9DU, England. [Lachmann, Robin H.; Murphy, Elaine] Natl Hosp Neurol & Neurosurg, London, England. [Mehta, Atul; Hughes, Derralyn] Royal Free Hosp, Lysosomal Storage Disorders Unit, London NW3 2QG, England. [Mehta, Atul; Hughes, Derralyn] UCL, London, England. [Kellman, Peter] NHLBI, NIH, Bethesda, MD 20892 USA. RP Moon, JC (reprint author), Heart Hosp, 16-18 Westmoreland St, London W1G 8PH, England. EM j.moon@ucl.ac.uk OI Treibel, Thomas/0000-0003-1560-7414; moon, james/0000-0001-8071-1491 FU British Heart Foundation [FS/10/40/28260, FS/12/56/29723]; Department of Health [DRF-2013-06-102] NR 29 TC 25 Z9 27 U1 1 U2 2 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1097-6647 EI 1532-429X J9 J CARDIOVASC MAGN R JI J. Cardiov. Magn. Reson. PD DEC 5 PY 2014 VL 16 AR 99 DI 10.1186/s12968-014-0099-4 PG 9 WC Cardiac & Cardiovascular Systems; Radiology, Nuclear Medicine & Medical Imaging SC Cardiovascular System & Cardiology; Radiology, Nuclear Medicine & Medical Imaging GA CB9IC UT WOS:000349944200001 PM 25475749 ER PT J AU Fountoulakis, KN Siamouli, M Moysidou, S Pantoula, E Moutou, K Panagiotidis, P Kemeridou, M Mavridou, E Loli, E Batsiari, E Preti, A Tondo, L Gonda, X Mobayed, N Akiskal, K Akiskal, H Costa, P McCrae, R AF Fountoulakis, Konstantinos N. Siamouli, Melina Moysidou, Stefania Pantoula, Eleonora Moutou, Katerina Panagiotidis, Panagiotis Kemeridou, Marina Mavridou, Eirini Loli, Efimia Batsiari, Elena Preti, Antonio Tondo, Leonardo Gonda, Xenia Mobayed, Nisreen Akiskal, Kareen Akiskal, Hagop Costa, Paul McCrae, Robert TI Standardization of the NEO-PI-3 in the Greek general population SO ANNALS OF GENERAL PSYCHIATRY LA English DT Article DE Five-factor personality inventory; NEO-PI-3; Standardization; Psychometrics ID NEO-PI-R; CONFIRMATORY FACTOR-ANALYSIS; PERSONALITY-INVENTORY; 5-FACTOR MODEL; DIMENSIONS; SCALE; CONSISTENCY; PSYCHOLOGY; ROTATION; VALIDITY AB Background: The revised NEO Personality Inventory (NEO-PI-3) includes 240 items corresponding to the Big Five personality traits (Extraversion, Agreeableness, Conscientiousness, Neuroticism, and Openness to Experience) and subordinate dimensions (facets). It is suitable for use with adolescents and adults (12 years or older). The aim of the current study was to validate the Greek translation of the NEO-PI-3 in the general Greek population. Material and methods: The study sample included 734 subjects from the general Greek population of whom 59.4% were females and 40.6% males aged 40.80 +/- 11.48. The NEO-PI-3 was translated into Greek and back-translated into English, and the accuracy of the translation was confirmed and established. The statistical analysis included descriptive statistics, confirmatory factorial analysis (CFA), the calculation of Cronbach's alpha, and the calculation of Pearson product-moment correlations. Sociodemographics groups were compared by ANOVA. Results: Most facets had Cronbach's alpha above 0.60. Confirmatory factor analysis showed acceptable loading of the facets on their own hypothesized factors and very good estimations of Cronbach's alphas for the hypothesized factors, so it was partially supportive of the five-factor structure of the NEO-PI-3. The factors extracted with Procrustes rotation analysis can be considered reasonably homologous to the factors of the American normative sample. Correlations between dimensions were as expected and similar to those reported in the literature. Discussion: The literature suggests that overall, the psychometric properties of NEO-PI-3 scales have been found to generalize across ages, cultures, and methods of measurement. In accord with this, the results of the current study confirm the reliability of the Greek translation and adaptation of the NEO-PI-3. The inventory has comparable psychometric properties in its Greek version in comparison to the original and other national translations, and it is suitable for clinical as well as research use. C1 [Fountoulakis, Konstantinos N.; Siamouli, Melina] Aristotle Univ Thessaloniki, Sch Med, Dept Psychiat 3, GR-54006 Thessaloniki, Greece. [Moysidou, Stefania; Pantoula, Eleonora; Moutou, Katerina; Kemeridou, Marina; Mavridou, Eirini] Aristotle Univ Thessaloniki, GR-54006 Thessaloniki, Greece. [Panagiotidis, Panagiotis] 424 Mil Hosp, Dept Psychiat, Thessaloniki, Greece. [Loli, Efimia] Mental Hlth Hosp Thessaloniki, Thessaloniki, Greece. [Preti, Antonio] Univ Cagliari, Univ Hosp, Ctr Liaison Psychiat & Psychosomat, I-09124 Cagliari, Italy. [Preti, Antonio] Ctr Med Genneruxi, Cagliari, Italy. [Tondo, Leonardo] Mood Ctr LucioBini, Cagliari, Italy. [Tondo, Leonardo] Mood Ctr LucioBini, Rome, Italy. [Tondo, Leonardo] Harvard Univ, Sch Med, McLean Hosp, Boston, MA USA. [Gonda, Xenia] Semmelweis Univ, Fac Med, Dept Clin & Theoret Mental Hlth, H-1085 Budapest, Hungary. [Mobayed, Nisreen] Univ Calif San Diego, Dept Psychiat, San Diego, CA 92103 USA. [Akiskal, Kareen] Studies Temperament & Creat, Paris, France. [Akiskal, Hagop] Univ Calif San Diego, Int Mood Ctr, San Diego, CA 92103 USA. [Costa, Paul] Biomed Res Ctr, Lab Behav Neurosci, Baltimore, MD USA. RP Fountoulakis, KN (reprint author), Aristotle Univ Thessaloniki, Sch Med, Dept Psychiat 3, GR-54006 Thessaloniki, Greece. EM kfount@med.auth.gr NR 53 TC 0 Z9 0 U1 2 U2 10 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1744-859X J9 ANN GEN PSYCHIATR JI Ann. Gen. Psychiatr. PD DEC 5 PY 2014 VL 13 AR 36 DI 10.1186/s12991-014-0036-9 PG 8 WC Psychiatry SC Psychiatry GA CB5ZN UT WOS:000349706600001 PM 25505930 ER PT J AU Waterfall, JJ Killian, JK Meltzer, PS AF Waterfall, Joshua J. Killian, J. Keith Meltzer, Paul S. TI The role of mutation of metabolism-related genes in genomic hypermethylation SO BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS LA English DT Review DE DNA methylation; Metabolism; Cancer; IDH; SDH; FH ID GASTROINTESTINAL STROMAL TUMORS; ACUTE MYELOID-LEUKEMIA; MITOCHONDRIAL RESPIRATORY-CHAIN; RENAL-CELL CARCINOMA; CHILDRENS ONCOLOGY GROUP; GERM-LINE MUTATIONS; COMPLEX-II GENE; SUCCINATE-DEHYDROGENASE; IDH2 MUTATIONS; ISOCITRATE DEHYDROGENASE AB Genetic mutations, metabolic dysfunction, and epigenetic misregulation are commonly considered to play distinct roles in tumor development and maintenance. However, intimate relationships between these mechanisms are now emerging. In particular, mutations in genes for the core metabolic enzymes IDH, SDH, and FH are significant drivers of diverse tumor types. In each case, the resultant accumulation of particular metabolites inhibits TET enzymes responsible for oxidizing 5-methylcytosine, leading to pervasive DNA hypermethylation. (C) 2014 Published by Elsevier Inc. C1 [Waterfall, Joshua J.; Killian, J. Keith; Meltzer, Paul S.] NCI, Ctr Canc Res, Genet Branch, Bethesda, MD 20892 USA. RP Meltzer, PS (reprint author), NCI, 37 Convent Dr, Bethesda, MD 20892 USA. EM pmeltzer@mail.nih.gov FU US NIH, NCI, CCR FX This work was supported by the Intramural Research Program of the US NIH, NCI, CCR. Marvin 14.7.14.0, 2014, ChemAxon (http://www.chemaxon.com) was used for drawing the chemical structures in Fig. 2. NR 116 TC 6 Z9 6 U1 1 U2 8 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0006-291X EI 1090-2104 J9 BIOCHEM BIOPH RES CO JI Biochem. Biophys. Res. Commun. PD DEC 5 PY 2014 VL 455 IS 1-2 BP 16 EP 23 DI 10.1016/j.bbrc.2014.08.003 PG 8 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA AX4GX UT WOS:000346892600004 PM 25111818 ER PT J AU Trang, H Brunet, JF Rohrer, H Gallego, J Amiel, J Bachetti, T Fischbeck, KH Similowski, T Straus, C Ceccherini, I Weese-Mayer, DE Frerick, M Bieganowska, K Middleton, L Morandi, F Ottonello, G AF Trang, Ha Brunet, Jean-Francois Rohrer, Hermann Gallego, Jorge Amiel, Jeanne Bachetti, Tiziana Fischbeck, Kenneth H. Similowski, Thomas Straus, Christian Ceccherini, Isabella Weese-Mayer, Debra E. Frerick, Matthias Bieganowska, Katarzyna Middleton, Linda Morandi, Francesco Ottonello, Giancarlo CA European Cent Hypoventilation Synd TI Proceedings of the fourth international conference on central hypoventilation SO ORPHANET JOURNAL OF RARE DISEASES LA English DT Review DE Central hypoventilation; Autonomic nervous system; Congenital central hypoventilation syndrome; PHOX2B gene; Hirschsprung's disease; Alanine expansion; Central control of breathing; Home mechanical ventilation; Phrenic nerve stimulation; Diaphragmatic stimulation ID CONGENITAL CENTRAL HYPOVENTILATION; BULBAR MUSCULAR-ATROPHY; HOME MECHANICAL VENTILATION; PACING STIMULATION SYSTEM; REPEAT ANDROGEN RECEPTOR; OBSTRUCTIVE SLEEP-APNEA; INFANT-DEATH-SYNDROME; POLYALANINE EXPANSIONS; PHOX2B MUTATIONS; IN-VITRO AB Central hypoventilation syndromes (CHS) are rare diseases of central autonomic respiratory control associated with autonomous nervous dysfunction. Severe central hypoventilation is the hallmark and the most life-threatening feature. CHS is a group of not-fully defined disorders. Congenital CHS (CCHS) (ORPHA661) is clinically and genetically well-characterized, with the disease-causing gene identified in 2003. CCHS presents at birth in most cases, and associated with Hirschsprung's disease (ORPHA99803) and neural crest tumours in 20% and 5% of cases, respectively. The incidence of CCHS is estimated to be 1 of 200,000 live births in France, yet remains unknown for the rest of the world. In contrast, late-onset CHS includes a group of not yet fully delineated diseases. Overlap with CCHS is likely, as a subset of patients harbours PHOX2B mutations. Another subset of patients present with associated hypothalamic dysfunction. The number of these patients is unknown (less than 60 cases reported worldwide). Treatment of CHS is palliative using advanced techniques of ventilation support during lifetime. Research is ongoing to better understand physiopathological mechanisms and identify potential treatment pathways. The Fourth International Conference on Central Hypoventilation was organised in Warsaw, Poland, April 13-15, 2012, under the patronage of the European Agency for Health and Consumers and Public Health European Agency of European Community. The conference provided a state-of-the-art update of knowledge on all the genetic, molecular, cellular, and clinical aspects of these rare diseases. C1 [Trang, Ha] Paris Diderot Univ, Robert Debre Univ Hosp, French Ctr Reference Cent Hypoventilat, EA REMES 7334, F-75019 Paris, France. [Brunet, Jean-Francois] Ecole Normale Super, CNRS 8197, INSERM 1024, IBENS, F-75231 Paris, France. [Rohrer, Hermann] Max Planck Inst Brain Res, Dept Neurochem, Res Grp Dev Neurobiol, Frankfurt, Germany. [Gallego, Jorge] Robert Debre Univ Hosp, Inserm U676, Paris, France. [Amiel, Jeanne] Necker Enfants Malades Univ Hosp, French Ctr Reference Cent Hypoventilat, Paris, France. [Bachetti, Tiziana] Ist Giannina Gaslini, I-16148 Genoa, Italy. [Fischbeck, Kenneth H.] NINDS, Neurogenet Branch, NIH, Bethesda, MD 20892 USA. [Similowski, Thomas; Straus, Christian] Univ Paris 06, La Pitie Salpetriere Univ Hosp, French Ctr Reference Cent Hypoventilat, Paris, France. [Ceccherini, Isabella] Ist Giannina Gaslini, Genet Mol Lab, I-16148 Genoa, Italy. [Weese-Mayer, Debra E.] Northwestern Univ, Feinberg Sch Med, Ann & Robert H Lurie Childrens Hosp Chicago, Auton Med Paediat CAMP, Chicago, IL 60611 USA. [Frerick, Matthias] Klinikum Dritter Orden, Munich, Germany. [Bieganowska, Katarzyna] Childrens Mem Hlth Inst Warsaw, Warsaw, Poland. [Middleton, Linda] Parent & UK CCHS Support Network, Oxford, England. [Morandi, Francesco] Osped Sacra Famiglia, Erba, Italy. RP Trang, H (reprint author), Paris Diderot Univ, Robert Debre Univ Hosp, French Ctr Reference Cent Hypoventilat, EA REMES 7334, 48 Blvd Serurier, F-75019 Paris, France. EM ha.trang@rdb.aphp.fr OI Brunet, Jean-Francois/0000-0002-1985-6103 NR 130 TC 2 Z9 3 U1 1 U2 10 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1750-1172 J9 ORPHANET J RARE DIS JI Orphanet J. Rare Dis. PD DEC 5 PY 2014 VL 9 AR 194 DI 10.1186/s13023-014-0194-5 PG 24 WC Genetics & Heredity; Medicine, Research & Experimental SC Genetics & Heredity; Research & Experimental Medicine GA AX7TX UT WOS:000347118600001 PM 25928806 ER PT J AU Ramamurthi, KS Storz, G AF Ramamurthi, Kumaran S. Storz, Gisela TI The small protein floodgates are opening; now the functional analysis begins SO BMC BIOLOGY LA English DT Editorial Material ID MULTIDRUG EFFLUX PUMP AB Aside from a few serendipitous discoveries, small proteins of less than 50 amino acids in bacteria and 100 amino acids in eukaryotes were largely ignored due to challenges in their genetic and biochemical detection. However, with the ever-increasing availability of completed genome sequences and deep sequencing, which allows analysis of genome-wide ribosome occupancy, hundreds of small proteins are now being identified. This brings to the forefront the challenges and opportunities associated with the characterization of these proteins. C1 [Ramamurthi, Kumaran S.] NCI, Mol Biol Lab, Bethesda, MD 20892 USA. [Storz, Gisela] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Cell Biol & Metab Program, Bethesda, MD 20892 USA. RP Ramamurthi, KS (reprint author), NCI, Mol Biol Lab, Bldg 37, Bethesda, MD 20892 USA. EM ramamurthiks@mail.nih.gov; storzg@mail.nih.gov RI Ramamurthi, Kumaran/P-3516-2015; OI Storz, Gisela/0000-0001-6698-1241 FU Intramural NIH HHS NR 10 TC 8 Z9 8 U1 1 U2 9 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1741-7007 J9 BMC BIOL JI BMC Biol. PD DEC 5 PY 2014 VL 12 AR 96 DI 10.1186/s12915-014-0096-y PG 3 WC Biology SC Life Sciences & Biomedicine - Other Topics GA AX2XD UT WOS:000346804800001 PM 25475548 ER PT J AU Harrison, SL Ding, J Tang, EYH Siervo, M Robinson, L Jagger, C Stephan, BCM AF Harrison, Stephanie L. Ding, Jie Tang, Eugene Y. H. Siervo, Mario Robinson, Louise Jagger, Carol Stephan, Blossom C. M. TI Cardiovascular Disease Risk Models and Longitudinal Changes in Cognition: A Systematic Review SO PLOS ONE LA English DT Article ID STROKE-FREE COHORT; ALZHEIMERS-DISEASE; DEMENTIA RISK; WHITEHALL II; POPULATION; DECLINE; SCORE; IMPAIRMENT; PREDICTION; PREVENTION AB Background: Cardiovascular disease and its risk factors have consistently been associated with poor cognitive function and incident dementia. Whether cardiovascular disease prediction models, developed to predict an individual's risk of future cardiovascular disease or stroke, are also informative for predicting risk of cognitive decline and dementia is not known. Objective: The objective of this systematic review was to compare cohort studies examining the association between cardiovascular disease risk models and longitudinal changes in cognitive function or risk of incident cognitive impairment or dementia. Materials and Methods: Medline, PsychINFO, and Embase were searched from inception to March 28, 2014. From 3,413 records initially screened, 21 were included. Results: The association between numerous different cardiovascular disease risk models and cognitive outcomes has been tested, including Framingham and non-Framingham risk models. Five studies examined dementia as an outcome; fourteen studies examined cognitive decline or incident cognitive impairment as an outcome; and two studies examined both dementia and cognitive changes as outcomes. In all studies, higher cardiovascular disease risk scores were associated with cognitive changes or risk of dementia. Only four studies reported model prognostic performance indices, such as Area Under the Curve (AUC), for predicting incident dementia or cognitive impairment and these studies all examined non-Framingham Risk models (AUC range: 0.74 to 0.78). Conclusions: Cardiovascular risk prediction models are associated with cognitive changes over time and risk of dementia. Such models are easily obtainable in clinical and research settings and may be useful for identifying individuals at high risk of future cognitive decline and dementia. C1 [Harrison, Stephanie L.; Tang, Eugene Y. H.; Robinson, Louise; Stephan, Blossom C. M.] Newcastle Univ, Inst Hlth & Soc, Newcastle Upon Tyne NE1 7RU, Tyne & Wear, England. [Ding, Jie] NIA, Lab Epidemiol & Populat Sci, NIH, Bethesda, MD 20892 USA. [Siervo, Mario; Jagger, Carol] Newcastle Univ, Inst Ageing & Hlth, Newcastle Upon Tyne NE1 7RU, Tyne & Wear, England. RP Harrison, SL (reprint author), Newcastle Univ, Inst Hlth & Soc, Newcastle Upon Tyne NE1 7RU, Tyne & Wear, England. EM s.harrison@newcastle.ac.uk RI Ding, Jie/K-9943-2015; OI Harrison, Stephanie/0000-0002-8846-0946; Robinson, Louise/0000-0003-0209-2503 FU Newcastle University FX This systematic review was completed as part of a PhD requirement for SLH, who receives a studentship from Newcastle University. These authors have no additional support or funding to report. NR 34 TC 11 Z9 11 U1 0 U2 8 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 5 PY 2014 VL 9 IS 12 AR e114431 DI 10.1371/journal.pone.0114431 PG 14 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA AX4MS UT WOS:000346907200087 PM 25478916 ER PT J AU Novelli, EM Hildesheim, M Rosano, C Vanderpool, R Simon, M Kato, GJ Gladwin, MT AF Novelli, Enrico M. Hildesheim, Mariana Rosano, Caterina Vanderpool, Rebecca Simon, Marc Kato, Gregory J. Gladwin, Mark T. TI Elevated Pulse Pressure is Associated with Hemolysis, Proteinuria and Chronic Kidney Disease in Sickle Cell Disease SO PLOS ONE LA English DT Article ID NITRIC-OXIDE BIOAVAILABILITY; BLOOD-PRESSURE; ENDOTHELIAL DYSFUNCTION; RELATIVE HYPERTENSION; CARDIOVASCULAR RISK; ANEMIA; HEMOGLOBIN; STROKE; COHORT; ADULTS AB A seeming paradox of sickle cell disease is that patients do not suffer from a high prevalence of systemic hypertension in spite of endothelial dysfunction, chronic inflammation and vasculopathy. However, some patients do develop systolic hypertension and increased pulse pressure, an increasingly recognized major cardiovascular risk factor in other populations. Hence, we hypothesized that pulse pressure, unlike other blood pressure parameters, is independently associated with markers of hemolytic anemia and cardiovascular risk in sickle cell disease. We analyzed the correlates of pulse pressure in patients (n = 661) enrolled in a multicenter international sickle cell trial. Markers of hemolysis were analyzed as independent variables and as a previously validated hemolytic index that includes multiple variables. We found that pulse pressure, not systolic, diastolic or mean arterial pressure, independently correlated with high reticulocyte count (beta = 2.37, p = 0.02) and high hemolytic index (beta = 1.53, p=0.002) in patients with homozygous sickle cell disease in two multiple linear regression models which include the markers of hemolysis as independent variables or the hemolytic index, respectively. Pulse pressure was also independently associated with elevated serum creatinine (beta = 3.21, p = 0.02), and with proteinuria (beta = 2.52, p = 0.04). These results from the largest sickle cell disease cohort to date since the Cooperative Study of Sickle Cell Disease show that pulse pressure is independently associated with hemolysis, proteinuria and chronic kidney disease. We propose that high pulse pressure may be a risk factor for clinical complications of vascular dysfunction in sickle cell disease. Longitudinal and mechanistic studies should be conducted to confirm these hypotheses. C1 [Novelli, Enrico M.; Vanderpool, Rebecca; Simon, Marc; Kato, Gregory J.] Univ Pittsburgh, Vasc Med Inst, Pittsburgh, PA 15260 USA. [Novelli, Enrico M.; Kato, Gregory J.] Univ Pittsburgh, Div Hematol & Oncol, Pittsburgh, PA USA. [Hildesheim, Mariana] NIH, Dept Crit Care Med, Bethesda, MD 20892 USA. [Rosano, Caterina] Univ Pittsburgh, Dept Epidemiol, Pittsburgh, PA USA. [Vanderpool, Rebecca; Simon, Marc] Univ Pittsburgh, Div Cardiol, Pittsburgh, PA USA. [Gladwin, Mark T.] Univ Pittsburgh, Vasc Med Inst, Div Pulm Allergy Crit Care Med, Pittsburgh, PA USA. RP Novelli, EM (reprint author), Univ Pittsburgh, Vasc Med Inst, Pittsburgh, PA 15260 USA. EM novellie@upmc.edu RI Kato, Gregory/I-7615-2014; OI Kato, Gregory/0000-0003-4465-3217; Rosano, Caterina/0000-0002-0909-1506; Rosano, Caterina/0000-0002-4271-6010 FU Institute for Transfusion Medicine; Hemophilia Center of Western Pennsylvania FX EMN, MH, RV, MS, GJK and MTG are supported by the Institute for Transfusion Medicine and the Hemophilia Center of Western Pennsylvania. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 36 TC 4 Z9 4 U1 0 U2 4 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA SN 1932-6203 J9 PLOS ONE JI PLoS One PD DEC 5 PY 2014 VL 9 IS 12 AR e114309 DI 10.1371/journal.pone.0114309 PG 14 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA AX4MS UT WOS:000346907200071 PM 25478953 ER PT J AU Kim, HS Li, AG Ahn, S Song, H Zhang, W AF Kim, Hong Sug Li, Aiguo Ahn, Susie Song, Hua Zhang, Wei TI Inositol Polyphosphate-5-Phosphatase F (INPP5F) inhibits STAT3 activity and suppresses gliomas tumorigenicity SO SCIENTIFIC REPORTS LA English DT Article ID EPIDERMAL-GROWTH-FACTOR; COILED-COIL DOMAIN; CELLULAR-TRANSFORMATION; TUMOR-SUPPRESSOR; GENE-REGULATION; STEM-CELLS; GLIOBLASTOMA; ACTIVATION; CANCER; PHOSPHORYLATION AB Glioblastoma (GBM), the most common type of primary malignant brain tumors harboring a subpopulation of stem-like cells (GSCs), is a fast-growing and often fatal tumor. Signal Transducer and Activator of Transcription 3 (STAT3) is one of the major signaling pathways in GSCs maintenance but the molecular mechanisms underlying STAT3 deregulation in GSCs are poorly defined. Here, we demonstrate that Inositol Polyphosphate-5-Phosphatase F (INPP5F), one of the polyphosphoinositide phosphatases, is differentially expressed in GSCs from glioma patients, and is identified as an inhibitor of STAT3 signaling via interaction with STAT3 and inhibition of its phosphorylation. Constitutively expressed INPP5F showed to suppress self-renewal and proliferation potentials of glioblastoma cells and reduced tumorigenicity of glioblastoma. In addition, loss of INPP5F gene in gliomas is significantly correlated with lower overall patient survivals. These findings suggest that INPP5F is a potential tumor suppressor in gliomas via inhibition of STAT3 pathway, and that deregulation of INPP5F may lead to contribution to gliomagenesis. C1 [Kim, Hong Sug] NCI, NeuroOncol Branch, Bethesda, MD 20892 USA. NINDS, NIH, Bethesda, MD 20892 USA. RP Kim, HS (reprint author), NCI, NeuroOncol Branch, Bethesda, MD 20892 USA. EM khongsug@gmail.com; zhangwe@mail.nih.gov FU Intramural Research Program of the NIH, National Cancer Institute, Center for Cancer Research; National Cancer Institute; Center for Cancer Research FX This study was supported by the Intramural Research Program of the NIH, National Cancer Institute, Center for Cancer Research. We thank Dr. Howard A. Fine for advices on this research project; and thank NINDS DNA Sequencing Facility for the helpful contributions to this work. We also thank NOB ABTC (Animal Brain Tumor Core) team members Rolanda K Bailey and Dionne Davis for assistance on mice experiments to this work. NR 34 TC 6 Z9 8 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 5 PY 2014 VL 4 AR 7330 DI 10.1038/srep07330 PG 10 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA AW4SF UT WOS:000346270100001 PM 25476455 ER PT J AU Huang, GW Wang, Y Wang, JP Yang, CZ Huang, T Zhuang, ZP Gu, J AF Huang, Guowei Wang, Yun Wang, Juping Yang, Chunzhang Huang, Tao Zhuang, Zhengping Gu, Jiang TI A morphologic and semi-quantitative technique to analyze synthesis and release of specific proteins in cells SO BMC CELL BIOLOGY LA English DT Article DE Morphology; Protein; Amino acid; Co-localization ID MAMMALIAN-CELLS; VISUALIZATION; NEURONS AB Background: With the rapid advancement of cell biology, the evaluation of a given protein's synthesis and release in cells becomes critical. However, up to now there has been no technique available to morphologically visualize and measure a newly synthesized protein in cells, nor can we measure the protein's release from the cells. Results: In this study, we developed a set of assays combining pulse chase amino acid substitution, non-radioactive labeling, and immunofluorescence co-localization to visualize newly synthesized proteins in individual cells and then to detect their release using modified ELISA. We demonstrated the synthesis and release of Bcl-2, MMP-9, and immunoglobulin G (IgG) in a human trophoblast cell line, of which the last finding has not been reported previously. Conclusions: This new technique offers a powerful tool to evaluate the dynamics of the synthesis and release of target proteins in individual cultured cells with wide applications in genetic and protein analysis. C1 [Huang, Guowei; Wang, Yun; Wang, Juping; Huang, Tao; Gu, Jiang] Shantou Univ, Coll Med, Dept Pathol & Pathophysiol, Guangdong Prov Key Lab Infect Dis & Immunopathol, Shantou 515041, Guangdong, Peoples R China. [Yang, Chunzhang; Zhuang, Zhengping] NINDS, Surg Neurol Branch, NIH, Bethesda, MD 20892 USA. RP Gu, J (reprint author), Shantou Univ, Coll Med, Dept Pathol & Pathophysiol, Guangdong Prov Key Lab Infect Dis & Immunopathol, Shantou 515041, Guangdong, Peoples R China. EM 2523381625@qq.com FU National Natural Science Foundation of China [81001199, 30971150] FX This work was supported by grants from the National Natural Science Foundation of China (81001199 to Z.C., 30971150 to J.G.). NR 14 TC 0 Z9 0 U1 1 U2 8 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1471-2121 J9 BMC CELL BIOL JI BMC Cell Biol. PD DEC 5 PY 2014 VL 15 AR 45 DI 10.1186/s12860-014-0045-1 PG 10 WC Cell Biology SC Cell Biology GA AW5HL UT WOS:000346306500001 PM 25476158 ER PT J AU Yue, MM Lv, K Meredith, SC Martindale, JL Gorospe, M Schuger, L AF Yue, Michael M. Lv, Kaosheng Meredith, Stephen C. Martindale, Jennifer L. Gorospe, Myriam Schuger, Lucia TI Novel RNA-binding Protein P311 Binds Eukaryotic Translation Initiation Factor 3 Subunit b (eIF3b) to Promote Translation of Transforming Growth Factor beta 1-3 (TGF-beta 1-3) SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article DE mRNA; Protein-Protein Interaction; RNA-binding Protein; Transforming Growth Factor (TGF-); Translation Initiation Factor ID 40S RIBOSOMAL-SUBUNIT; MESSENGER-RNA; SACCHAROMYCES-CEREVISIAE; INHIBITS PROLIFERATION; CROSS-LINKING; PCI DOMAIN; WD-REPEAT; TGF-BETA; CANCER; COMPLEX AB Background: P311 is a stimulator of TGF-1-3 translation, but its mechanism of action is unknown. Results: P311 binds eIF3b and the 5UTRs of TGF-1-3 mRNAs. Thereby, P311 recruits TGF-1-3 mRNAs to the translation machinery. Conclusion: P311 is an RNA-binding protein that binds to eIF3b to stimulate TGF-1-3 translation. Significance: Our studies add a new level of complexity to TGF- signaling regulation. P311, a conserved 8-kDa intracellular protein expressed in brain, smooth muscle, regenerating tissues, and malignant glioblastomas, represents the first documented stimulator of TGF-1-3 translation in vitro and in vivo. Here we initiated efforts to define the mechanism underlying P311 function. PONDR (R) (Predictor Of Naturally Disordered Regions) analysis suggested and CD confirmed that P311 is an intrinsically disordered protein, therefore requiring an interacting partner to acquire tertiary structure and function. Immunoprecipitation coupled with mass spectroscopy identified eIF3 subunit b (eIF3b) as a novel P311 binding partner. Immunohistochemical colocalization, GST pulldown, and surface plasmon resonance studies revealed that P311-eIF3b interaction is direct and has a K-d of 1.26 m. Binding sites were mapped to the non-canonical RNA recognition motif of eIF3b and a central 11-amino acid-long region of P311, here referred to as eIF3b binding motif. Disruption of P311-eIF3b binding inhibited translation of TGF-1, 2, and 3, as indicated by luciferase reporter assays, polysome fractionation studies, and Western blot analysis. RNA precipitation assays after UV cross-linking and RNA-protein EMSA demonstrated that P311 binds directly to TGF- 5UTRs mRNAs through a previously unidentified RNA recognition motif-like motif. Our results demonstrate that P311 is a novel RNA-binding protein that, by interacting with TGF-s 5UTRs and eIF3b, stimulates the translation of TGF-1, 2, and 3. C1 [Yue, Michael M.; Lv, Kaosheng; Meredith, Stephen C.; Schuger, Lucia] Univ Chicago, Dept Pathol, Chicago, IL 60637 USA. [Meredith, Stephen C.] Univ Chicago, Dept Biochem & Mol Biol, Chicago, IL 60637 USA. [Martindale, Jennifer L.; Gorospe, Myriam] NIA, Genet Lab, NIH, Baltimore, MD 21224 USA. RP Schuger, L (reprint author), Univ Chicago, Dept Pathol, 5841 S Maryland Ave, Chicago, IL 60637 USA. EM lschuger@bsd.uchicago.edu FU National Institutes of Health [R01GM111116]; American Heart Association; NIA, National Institutes of Health FX This work was supported, in whole or in part, by National Institutes of Health Grant R01GM111116 (to L. S.). This work was also supported by an award from the American Heart Association (to M. M. Y.).; Supported by the Intramural Research Program of the NIA, National Institutes of Health. NR 72 TC 7 Z9 8 U1 0 U2 14 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 EI 1083-351X J9 J BIOL CHEM JI J. Biol. Chem. PD DEC 5 PY 2014 VL 289 IS 49 BP 33971 EP 33983 DI 10.1074/jbc.M114.609495 PG 13 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA AW1UZ UT WOS:000346077600025 PM 25336651 ER PT J AU Soncini, D Caffa, I Zoppoli, G Cea, M Cagnetta, A Passalacqua, M Mastracci, L Boero, S Montecucco, F Sociali, G Lasiglie, D Damonte, P Grozio, A Mannino, E Poggi, A D'Agostino, VG Monacelli, F Provenzani, A Odetti, P Ballestrero, A Bruzzone, S Nencioni, A AF Soncini, Debora Caffa, Irene Zoppoli, Gabriele Cea, Michele Cagnetta, Antonia Passalacqua, Mario Mastracci, Luca Boero, Silvia Montecucco, Fabrizio Sociali, Giovanna Lasiglie, Denise Damonte, Patrizia Grozio, Alessia Mannino, Elena Poggi, Alessandro D'Agostino, Vito G. Monacelli, Fiammetta Provenzani, Alessandro Odetti, Patrizio Ballestrero, Alberto Bruzzone, Santina Nencioni, Alessio TI Nicotinamide Phosphoribosyltransferase Promotes Epithelial-to-Mesenchymal Transition as a Soluble Factor Independent of Its Enzymatic Activity SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article DE Breast Cancer; Epithelial-Mesenchymal Transition (EMT); Nicotinamide Adenine Dinucleotide (NAD); Secretion; Signaling ID COLONY-ENHANCING FACTOR; BREAST-CANCER; BIOSYNTHETIC ENZYME; METABOLIC SYNDROME; NAD BIOSYNTHESIS; VISFATIN LEVELS; SERUM VISFATIN; INFLAMMATION; SIRTUINS; CELLS AB Background: Nicotinamide phosphoribosyltransferase (NAMPT) acts both as an enzyme in the production of the coenzyme NAD(+) and as a secreted cytokine. Results: In breast cancer cells, NAMPT induces the epithelial-to-mesenchymal transition, a process that underlies metastasis, as a secreted protein independent of its enzymatic activity. Conclusion: Secreted NAMPT promotes epithelial-to-mesenchymal transition. Significance: Extracellular NAMPT neutralization may be of therapeutic value. Boosting NAD(+) biosynthesis with NAD(+) intermediates has been proposed as a strategy for preventing and treating age-associated diseases, including cancer. However, concerns in this area were raised by observations that nicotinamide phosphoribosyltransferase (NAMPT), a key enzyme in mammalian NAD(+) biosynthesis, is frequently up-regulated in human malignancies, including breast cancer, suggesting possible protumorigenic effects for this protein. We addressed this issue by studying NAMPT expression and function in human breast cancer in vivo and in vitro. Our data indicate that high NAMPT levels are associated with aggressive pathological and molecular features, such as estrogen receptor negativity as well as HER2-enriched and basal-like PAM50 phenotypes. Consistent with these findings, we found that NAMPT overexpression in mammary epithelial cells induced epithelial-to-mesenchymal transition, a morphological and functional switch that confers cancer cells an increased metastatic potential. However, importantly, NAMPT-induced epithelial-to-mesenchymal transition was found to be independent of NAMPT enzymatic activity and of the NAMPT product nicotinamide mononucleotide. Instead, it was mediated by secreted NAMPT through its ability to activate the TGF signaling pathway via increased TGF1 production. These findings have implications for the design of therapeutic strategies exploiting NAD(+) biosynthesis via NAMPT in aging and cancer and also suggest the potential of anticancer agents designed to specifically neutralize extracellular NAMPT. Notably, because high levels of circulating NAMPT are found in obese and diabetic patients, our data could also explain the increased predisposition to cancer of these subjects. C1 [Soncini, Debora; Caffa, Irene; Cea, Michele; Montecucco, Fabrizio; Lasiglie, Denise; Damonte, Patrizia; Monacelli, Fiammetta; Odetti, Patrizio; Ballestrero, Alberto; Nencioni, Alessio] Univ Genoa, Dept Internal Med, I-16132 Genoa, Italy. [Passalacqua, Mario; Sociali, Giovanna; Grozio, Alessia; Mannino, Elena; Bruzzone, Santina] Univ Genoa, Dept Expt Med, Biochem Sect, I-16132 Genoa, Italy. [Sociali, Giovanna; Grozio, Alessia; Mannino, Elena; Bruzzone, Santina] Univ Genoa, Ctr Excellence Biomed Res, I-16132 Genoa, Italy. [Mastracci, Luca] Univ Genoa, Pathol Unit, Dept Integrated Surg & Diagnost Sci, I-16132 Genoa, Italy. [Zoppoli, Gabriele] Univ Libre Bruxelles, Inst Jules Bordet, B-1000 Brussels, Belgium. [Zoppoli, Gabriele] NCI, Mol Pharmacol Lab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. [Cea, Michele; Cagnetta, Antonia] Harvard Univ, Sch Med, Boston Novartis Inst BioMed Res, Jerome Lipper Multiple Myeloma Ctr,Dana Farber Ca, Cambridge, MA 02139 USA. [Mastracci, Luca; Boero, Silvia; Poggi, Alessandro; Odetti, Patrizio; Ballestrero, Alberto; Nencioni, Alessio] Azienda Osped Univ San Martino, Ist Ricovero & Cura Carattere Sci, Ist Nazl Ric Cancro, Ist Sci Tumori, I-16132 Genoa, Italy. [Montecucco, Fabrizio] Univ Geneva, Div Cardiol, Fdn Med Res, Dept Med Specialties, CH-1211 Geneva, Switzerland. [D'Agostino, Vito G.; Provenzani, Alessandro] Univ Trent, Ctr Integrat Biol, Lab Genom Screening, I-38123 Trento, Italy. [Passalacqua, Mario] Univ Genoa, Italian Inst Biostruct & Biosyst, I-16132 Genoa, Italy. RP Nencioni, A (reprint author), Univ Genoa, Dept Internal Med, Vle Benedetto 15 6, I-16132 Genoa, Italy. EM alessio.nencioni@unige.it RI Bruzzone, Santina/A-4264-2015; Zoppoli, Gabriele/B-6935-2016; Caffa, Irene/J-9835-2016; Provenzani, Alessandro/I-9211-2012; Poggi, Alessandro/K-6664-2016; Montecucco, Fabrizio/K-8543-2016; OI Passalacqua, Mario/0000-0003-2779-6259; D'AGOSTINO, VITO/0000-0003-3379-2254; Bruzzone, Santina/0000-0003-2034-3716; Zoppoli, Gabriele/0000-0003-3890-5588; Caffa, Irene/0000-0003-1111-9915; Provenzani, Alessandro/0000-0003-1652-3415; Poggi, Alessandro/0000-0002-1860-430X; Montecucco, Fabrizio/0000-0003-0823-8729; MONACELLI, FIAMMETTA/0000-0003-4303-7252; ODETTI, PATRIZIO/0000-0001-9559-7273 FU Associazione Italiana per la Ricerca sul Cancro [6108]; Seventh Framework Project PANACREAS [256986]; Italian Ministry of Health [GR-2008-1135635]; Compagnia di San Paolo; Fondazione Umberto Veronesi; University of Genoa; PO CRO Fondo Sociale Europeo Regione Liguria Asse IV "Capitale Umano"; Swiss National Science Foundation [310030_152639/1] FX This work was supported in part by Associazione Italiana per la Ricerca sul Cancro Grant 6108 (to A. N.), by Seventh Framework Project PANACREAS Grant 256986 (to A. N.), by Italian Ministry of Health Project Grant GR-2008-1135635 (to A. N.), by the Compagnia di San Paolo (to A. N.), by the Fondazione Umberto Veronesi (to A. N.), by the University of Genoa, by the PO CRO Fondo Sociale Europeo Regione Liguria 2007-2013 Asse IV "Capitale Umano" (to S. Boero), and by Swiss National Science Foundation Grant 310030_152639/1 (to F. M.). NR 52 TC 19 Z9 19 U1 0 U2 7 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 EI 1083-351X J9 J BIOL CHEM JI J. Biol. Chem. PD DEC 5 PY 2014 VL 289 IS 49 BP 34189 EP 34204 DI 10.1074/jbc.M114.594721 PG 16 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA AW1UZ UT WOS:000346077600042 PM 25331943 ER PT J AU Yaffe, D Vergara-Jaque, A Shuster, Y Listov, D Meena, S Singh, SK Forrest, LR Schuldiner, S AF Yaffe, Dana Vergara-Jaque, Ariela Shuster, Yonatan Listov, Dina Meena, Sitaram Singh, Satinder K. Forrest, Lucy R. Schuldiner, Shimon TI Functionally Important Carboxyls in a Bacterial Homologue of the Vesicular Monoamine Transporter (VMAT) SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article DE Antibiotic Resistance; Membrane Transport; Multidrug Transporter; Neurotransmitter; Neurotransmitter Transport; Proton Transport ID MAJOR FACILITATOR SUPERFAMILY; MULTIPLE SEQUENCE ALIGNMENT; PROTEIN SECONDARY STRUCTURE; MULTIDRUG TRANSPORTER; ESCHERICHIA-COLI; NEUROTRANSMITTER TRANSPORTERS; STRUCTURE PREDICTION; ALTERNATING ACCESS; RESERPINE BINDING; MEMBRANE-PROTEINS AB Background: Bacterial homologues of neurotransporters served as structural paradigms for interpretation of the functional data available for their eukaryotic counterparts. Results: We identified and characterized a close bacterial homologue of the rat vesicular monoamine transporter rVMAT2. Conclusion: BbMAT is a multidrug antiporter. Conserved membrane-embedded carboxyls play a role in substrate and proton transport. Significance: Understanding of the bacterial homologue should provide insights into rVMAT2. Transporters essential for neurotransmission in mammalian organisms and bacterial multidrug transporters involved in antibiotic resistance are evolutionarily related. To understand in more detail the evolutionary aspects of the transformation of a bacterial multidrug transporter to a mammalian neurotransporter and to learn about mechanisms in a milieu amenable for structural and biochemical studies, we identified, cloned, and partially characterized bacterial homologues of the rat vesicular monoamine transporter (rVMAT2). We performed preliminary biochemical characterization of one of them, Brevibacillus brevis monoamine transporter (BbMAT), from the bacterium B. brevis. BbMAT shares substrates with rVMAT2 and transports them in exchange with >1H(+), like the mammalian transporter. Here we present a homology model of BbMAT that has the standard major facilitator superfamily fold; that is, with two domains of six transmembrane helices each, related by 2-fold pseudosymmetry whose axis runs normal to the membrane and between the two halves. The model predicts that four carboxyl residues, a histidine, and an arginine are located in the transmembrane segments. We show here that two of the carboxyls are conserved, equivalent to the corresponding ones in rVMAT2, and are essential for H+-coupled transport. We conclude that BbMAT provides an excellent experimental paradigm for the study of its mammalian counterparts and bacterial multidrug transporters. C1 [Yaffe, Dana; Shuster, Yonatan; Listov, Dina; Schuldiner, Shimon] Hebrew Univ Jerusalem, Alexander Silberman Inst Life Sci, Dept Biol Chem, IL-91904 Jerusalem, Israel. [Vergara-Jaque, Ariela; Forrest, Lucy R.] NINDS, Computat Struct Biol Sect, NIH, Bethesda, MD 20852 USA. [Meena, Sitaram; Singh, Satinder K.] Yale Univ, Sch Med, Dept Cellular & Mol Physiol, New Haven, CT 06520 USA. RP Schuldiner, S (reprint author), Hebrew Univ Jerusalem, Alexander Silberman Inst Life Sci, Dept Biol Chem, IL-91904 Jerusalem, Israel. EM shimon.schuldiner@huji.ac.il FU National Institutes of Health [NS16708, R21MH098180]; Division of Intramural Research of the NINDS, National Institutes of Health; Israel-USA Binational Science Foundation; L'Oreal Chile-UNESCO Women in Science fellowship FX This work was supported, in whole or in part, by National Institutes of Health Grants NS16708 (to S. S.) and R21MH098180 (to S. K. S.) and by the Division of Intramural Research of the NINDS, National Institutes of Health (to L. R. F. and A. V. J.). This work was also supported by the Israel-USA Binational Science Foundation (to S. S. and S. K. S.).; Recipient of the L'Oreal Chile-UNESCO Women in Science fellowship. NR 68 TC 1 Z9 1 U1 0 U2 9 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 EI 1083-351X J9 J BIOL CHEM JI J. Biol. Chem. PD DEC 5 PY 2014 VL 289 IS 49 BP 34229 EP 34240 DI 10.1074/jbc.M114.607366 PG 12 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA AW1UZ UT WOS:000346077600045 PM 25336661 ER PT J AU Yoon, J Feng, XX Kim, YS Shin, DM Hatzi, K Wang, HS Morse, HC AF Yoon, Jeongheon Feng, Xianxum Kim, Yong-Soo Shin, Dong-Mi Hatzi, Katerina Wang, Hongsheng Morse, Herbert C., III TI Interferon Regulatory Factor 8 (IRF8) Interacts with the B Cell Lymphoma 6 (BCL6) Corepressor BCOR SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article DE Gene Expression; Immunology; Lymphocyte; Protein Complex; Protein-Protein Interaction; Transcription Repressor ID SEQUENCE-BINDING-PROTEIN; GERMINAL-CENTER; COMPLEX-FORMATION; PROGENITOR CELLS; GENE-EXPRESSION; DENDRITIC CELLS; ICSBP; DOMAIN; ACTIVATION; LINEAGE AB Background: Protein partnerships regulate specific functions of cells. BCOR protein-protein interactions are critical to aspects of B cell biology. Results: IRF8 pairs with BCOR in the nucleus to enhance its transcriptional repressive activity. Conclusion: Partnering of IRF8 with BCOR defines a novel mechanism for controlling B cell gene expression. Significance: Understanding gene regulation in specific cell types requires identification of protein complexes that modulate expression. B cell lymphoma 6 (BCL6) corepressor (BCOR) was discovered as a BCL6-interacting corepressor, but little is known about its other biological activities in normal B cell development and function. Previously, we found that interferon regulatory factor 8 (IRF8), also known as interferon consensus sequence-binding protein, directly targets a large number of genes in germinal center B cells including BCL6. In this study, we screened potential binding partners of IRF8 using a retrovirus-based protein complementation assay screen in a mouse pre-B cell line. We found that IRF8 interacts directly with BCOR and that the -helical region of IRF8 and the BCL6 binding domain of BCOR are required for this interaction. In addition, IRF8 protein interacts directly with BCL6. Using an siRNA-mediated IRF8 knockdown mouse B cell lymphoma cell line, we showed that IRF8 represses Bcor and enhances Bcl6 transcription. Taken together, these data suggest that a complex comprising BCOR-BCL6-IRF8 modulates BCL6-associated transcriptional regulation of germinal center B cell function. C1 [Yoon, Jeongheon; Feng, Xianxum; Kim, Yong-Soo; Shin, Dong-Mi; Wang, Hongsheng; Morse, Herbert C., III] NIAID, Immunogenet Lab, NIH, Rockville, MD 20852 USA. [Hatzi, Katerina] Weill Cornell Med Coll, Dept Med, Div Hematol & Med Oncol, New York, NY 10065 USA. [Hatzi, Katerina] Weill Cornell Med Coll, Dept Pharmacol, New York, NY 10065 USA. RP Morse, HC (reprint author), NIAID, Virol & Cellular Immunol Sect, Immunogenet Lab, NIH, 5640 Fisher Lane, Rockville, MD 20852 USA. EM hmorse@niaid.nih.gov OI Morse, Herbert/0000-0002-9331-3705 FU National Institutes of Health Intramural Research Program of the NIAID FX This work was supported, in whole or in part, by the National Institutes of Health Intramural Research Program of the NIAID. NR 41 TC 4 Z9 4 U1 0 U2 0 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 EI 1083-351X J9 J BIOL CHEM JI J. Biol. Chem. PD DEC 5 PY 2014 VL 289 IS 49 BP 34250 EP 34257 DI 10.1074/jbc.M114.571182 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA AW1UZ UT WOS:000346077600047 PM 25331958 ER PT J AU Kim, CJ Kovacs, C Chun, TW Kandel, G Osborne, BJW Huibner, S Shahabi, K Yue, FY Benko, E Ostowski, M Kaul, R AF Kim, Connie J. Kovacs, Colin Chun, Tae-Wook Kandel, Gabor Osborne, Brendan J. W. Huibner, Sanja Shahabi, Kamnoosh Yue, Feng-Yun Benko, Erika Ostowski, Mario Kaul, Rupert TI Antiretroviral Therapy in HIV-Infected Elite Controllers: Impact on Gut Immunology, Microbial Translocation, and Biomarkers of Serious Non-AIDS Conditions SO JAIDS-JOURNAL OF ACQUIRED IMMUNE DEFICIENCY SYNDROMES LA English DT Article DE HIV; elite controllers; antiretroviral therapy; gut immunology; microbial translocation; serious non-AIDS conditions; inflammation ID IMMUNE ACTIVATION; CELLS; TH17 AB Elite controllers (ECs) maintain undetectable HIV viral loads without antiretroviral therapy (ART) but are at increased risk of serious non-AIDS conditions (SNA). We assessed the impact of ART in ECs on gut immune dysfunction and biomarkers predicting SNA (blood CD4/CD8 ratio, plasma IL-6, D-dimer levels). At baseline, ECs had elevated IL-6 and D-dimer levels and reduced CD4/CD8 ratio compared with HIV-uninfected controls, but no difference in microbial translocation or gut CD4 subsets. ART increased CD4/CD8 ratio but did not normalize IL-6 and D-dimer levels. EC SNA pathogenesis may be independent of gut immune dysfunction, and resolution may require prolonged ART. C1 [Kim, Connie J.; Osborne, Brendan J. W.; Huibner, Sanja; Shahabi, Kamnoosh; Yue, Feng-Yun; Ostowski, Mario; Kaul, Rupert] Univ Toronto, Dept Med & Immunol, Toronto, ON, Canada. [Kovacs, Colin; Benko, Erika] Maple Leaf Med Clin, Toronto, ON, Canada. [Chun, Tae-Wook] NIAID, NIH, Bethesda, MD 20892 USA. [Kandel, Gabor] St Michaels Hosp, Dept Gastroenterol, Toronto, ON M5B 1W8, Canada. [Kandel, Gabor] Li Ka Shing Knowledge Inst, Toronto, ON, Canada. RP Kaul, R (reprint author), Dept Med & Immunol, 6356 Med Sci Bldg,1 Kings Coll Circle, Toronto, ON M5S 1A8, Canada. EM rupert.kaul@utoronto.ca FU Ontario HIV Treatment Network [ROGB-G123]; Canadian Institutes of Health Research/Canadian Digestive Health Foundation (CIHR/CDHF); CIHR (Emerging HIV Team Grant) [HET85518]; Canadian Research Chair Program; Intramural Research Program of the National Institutes of Allergy and Infectious Diseases, National Institute of Health FX Supported in part by the Ontario HIV Treatment Network (R.K., ROGB-G123); the Canadian Institutes of Health Research/Canadian Digestive Health Foundation (CIHR/CDHF; C.J.K., salary award); a CIHR (Emerging HIV Team Grant HET85518); Canadian Research Chair Program (R.K., salary support); and the Intramural Research Program of the National Institutes of Allergy and Infectious Diseases, National Institute of Health. NR 14 TC 3 Z9 3 U1 0 U2 6 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1525-4135 EI 1077-9450 J9 JAIDS-J ACQ IMM DEF JI JAIDS PD DEC 5 PY 2014 VL 67 IS 5 BP 514 EP 518 PG 5 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA AT2NW UT WOS:000344772300013 PM 25393939 ER PT J AU Avila, I Lin, SC AF Avila, Irene Lin, Shih-Chieh TI Distinct neuronal populations in the basal forebrain encode motivational salience and movement SO FRONTIERS IN BEHAVIORAL NEUROSCIENCE LA English DT Article DE basal forebrain; ventral pallidum; motivational salience; movement; fixation; rat ID INCENTIVE SALIENCE; PALLIDAL NEURONS; VENTRAL PALLIDUM; GLOBUS-PALLIDUS; RAT; SYSTEMS; CORTEX; BRAIN; PROJECTIONS; RESPONSES AB Basal forebrain (BF) is one of the largest cortically projecting neuromodulatory systems in the mammalian brain, and plays a key role in attention, arousal, learning and memory. The cortically projecting BE neurons, comprised of mainly magnocellular cholinergic and GABAergic neurons, are widely distributed across several brain regions that spatially overlap with the ventral striatopallidal system at the ventral pallidurn (VP). As a first step toward untangling the respective functions of spatially overlapping BF and VP systems, the goal of this study was to comprehensively characterize the behavioral correlates and physiological properties of heterogeneous neuronal populations in the BE region. We found that, while rats performed a reward-biased simple reaction time task, distinct neuronal populations encode either motivational salience or movement information. The motivational salience of attended stimuli is encoded by phasic bursting activity of a large population of slow-firing neurons that have large, broad, and complex action potential waveforms. In contrast, two other separate groups of neurons encode movement related information, and respectively increase and decrease firing rates while rats maintained fixation. These two groups of neurons mostly have higher firing rates and small, narrow action potential waveforms. These results support the conclusion that multiple neurophysiologically distinct neuronal populations in the BE region operate independently of each other as parallel functional circuits. These observations also caution against interpreting neuronal activity in this region as a homogeneous population reflecting the function of either BE or VP alone. We suggest that salience- and movement-related neuronal populations likely correspond to BE corticopetal neurons and VP neurons, respectively C1 [Avila, Irene; Lin, Shih-Chieh] NIA, Neural Circuits & Cognit Unit, Lab Behav Neurosci, NIH, Baltimore, MD 21224 USA. RP Lin, SC (reprint author), NIA, Neural Circuits & Cognit Unit, Lab Behav Neurosci, NIH, 251 Bayview Blvd,Suite 100,9C220, Baltimore, MD 21224 USA. EM shih-chieh.lin@nih.gov OI Lin, Shih-Chieh/0000-0003-3693-5476 FU National Institute on Aging, NIH FX This research is funded by the intramural research program of the National Institute on Aging, NIH. We thank S. M. Raver, K. Vlasov, P. R. Rapp for critical discussions and reading of the manuscript; G. Nelson, H. M. V Manzur and B. Brock for technical help. NR 35 TC 8 Z9 8 U1 0 U2 2 PU FRONTIERS RESEARCH FOUNDATION PI LAUSANNE PA PO BOX 110, LAUSANNE, 1015, SWITZERLAND SN 1662-5153 J9 FRONT BEHAV NEUROSCI JI Front. Behav. Neurosci. PD DEC 4 PY 2014 VL 8 AR 421 DI 10.3389/fnbeh.2014.00421 PG 12 WC Behavioral Sciences; Neurosciences SC Behavioral Sciences; Neurosciences & Neurology GA AZ0PG UT WOS:000347946600001 PM 25538586 ER PT J AU Uldrick, TS Polizzotto, MN Aleman, K Wyvill, KM Marshall, V Whitby, D Wang, V Pittaluga, S O'Mahony, D Steinberg, SM Little, RF Yarchoan, R AF Uldrick, Thomas S. Polizzotto, Mark N. Aleman, Karen Wyvill, Kathleen M. Marshall, Vickie Whitby, Denise Wang, Victoria Pittaluga, Stefania O'Mahony, Deirdre Steinberg, Seth M. Little, Richard F. Yarchoan, Robert TI Rituximab plus liposomal doxorubicin in HIV-infected patients with KSHV-associated multicentric Castleman disease SO BLOOD LA English DT Article ID SARCOMA-ASSOCIATED HERPESVIRUS; NON-HODGKIN-LYMPHOMA; PRIMARY EFFUSION LYMPHOMA; FREE LIGHT-CHAINS; ACQUIRED IMMUNODEFICIENCY SYNDROME; KAPOSIS-SARCOMA; DNA-SEQUENCES; B-CELLS; VIRAL INTERLEUKIN-6; MONOCLONAL-ANTIBODY AB Kaposisarcoma(KS) herpesvirus-associated multicentric Castleman disease(KSHV-MCD) is a lymphoproliferative disorder, most commonly seen in HIV-infected patients, that has a high mortality if untreated. Concurrent KS is common. Although rituximab has reported activity in KSHV-MCD, its use is often associated with KS progression. Within a natural history study of KSHV-MCD, we prospectively evaluated rituximab 375 mg/m(2) combined with liposomal doxorubicin 20 mg/m(2) (R-Dox) every 3 weeks in 17 patients. Patients received a median of 4 cycles (range 3-9). All received antiretroviral therapy, 11 received consolidation interferon-alpha, and 6 received consolidation high-dose zidovudine with valganciclovir. Using NCI KSHV-MCD response criteria, major clinical and biochemical responses were attained in 94% and 88% of patients, respectively. With a median 58 months' potential follow-up, 3-year event-free survival was 69% and 3-year overall survival was 81%. During R-Dox therapy, cutaneous KS developed in 1 patient, whereas 5 of 6 patients with it had clinical improvement. R-Dox was associated with significant improvement in anemia and hypoalbuminemia. KSHV viral load, KSHV viral interleukin-6, C-reactive protein, humaninterleukin-6, and serum immunoglobulin free light chains decreased with therapy. R-Dox is effective in symptomatic KSHV-MCD and may be useful in patients with concurrent KS. This trial was registered at www.clinicaltrials.gov as #NCT00092222. C1 [Uldrick, Thomas S.; Polizzotto, Mark N.; Aleman, Karen; Wyvill, Kathleen M.; Wang, Victoria; O'Mahony, Deirdre; Little, Richard F.; Yarchoan, Robert] NCI, HIV & AIDS Malignancy Branch, Ctr Canc Res, Bethesda, MD 20892 USA. [Marshall, Vickie; Whitby, Denise] NCI, AIDS & Canc Virus Program, Viral Oncol Sect, Leidos Frederick, Frederick, MD 21701 USA. [Pittaluga, Stefania] NCI, Pathol Lab, Bethesda, MD 20892 USA. [Steinberg, Seth M.] NCI, Biostat & Data Management Sect, Ctr Canc Res, Bethesda, MD 20892 USA. RP Uldrick, TS (reprint author), NCI, HIV & AIDS Malignancy Branch, 10 Ctr Dr 6N106, Bethesda, MD 20892 USA. EM uldrickts@mail.nih.gov; Robert.Yarchoan@nih.gov FU NCI, NIH [HHSN261200800001E] FX This work was supported in part by the Intramural Research Program, NCI, NIH, and a grant from the NCI, NIH (HHSN261200800001E). NR 67 TC 14 Z9 14 U1 0 U2 7 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 2021 L ST NW, SUITE 900, WASHINGTON, DC 20036 USA SN 0006-4971 EI 1528-0020 J9 BLOOD JI Blood PD DEC 4 PY 2014 VL 124 IS 24 BP 3544 EP 3552 DI 10.1182/blood-2014-07-586800 PG 9 WC Hematology SC Hematology GA AY3DZ UT WOS:000347465900009 PM 25331113 ER PT J AU Iqbal, MB Johns, M Cao, J Liu, Y Yu, SC Hyde, GD Laffan, MA Marchese, FP Cho, SH Clark, AR Gavins, FN Woollard, KJ Blackshear, PJ Mackman, N Dean, JL Boothby, M Haskard, DO AF Iqbal, M. Bilal Johns, Michael Cao, Jun Liu, Yu Yu, Sheng-Chun Hyde, Gareth D. Laffan, Michael A. Marchese, Francesco P. Cho, Sung Hoon Clark, Andrew R. Gavins, Felicity N. Woollard, Kevin J. Blackshear, Perry J. Mackman, Nigel Dean, Jonathan L. Boothby, Mark Haskard, Dorian O. TI PARP-14 combines with tristetraprolin in the selective posttranscriptional control of macrophage tissue factor expression SO BLOOD LA English DT Article ID MESSENGER-RNA DECAY; HUMAN ENDOTHELIAL-CELLS; HUMAN MONOCYTIC CELLS; ZINC-FINGER PROTEINS; FACTOR GENE; ATHEROSCLEROTIC PLAQUE; TTP GENE; KAPPA-B; BINDING; CANCER AB Tissue factor (TF) (CD142) is a 47 kDa transmembrane cell surface glycoprotein that triggers the extrinsic coagulation cascade and links thrombosis with inflammation. Although macrophage TF expression is known to be regulated at the RNA level, very little is known about the mechanisms involved. Poly(adenosine 5'-diphosphate [ADP]-ribose)-polymerase (PARP)-14 belongs to a family of intracellular proteins that generate ADP-ribose posttranslational adducts. Functional screening of PARP-14-deficient macrophages mice revealed that PARP-14 deficiency leads to increased TF expression and functional activity in macrophages after challenge with bacterial lipopolysaccharide. This was related to an increase in TF messenger RNA (mRNA) stability. Ribonucleoprotein complex immunoprecipitation and biotinylated RNA pull-down assays demonstrated that PARP-14 forms a complex with the mRNA-destabilizing protein tristetraprolin (TTP) and a conserved adenylate-uridylate-rich element in the TF mRNA 3' untranslated region. TF mRNA regulation by PARP-14 was selective, as tumor necrosis factor (TNF)alpha mRNA, which is also regulated by TTP, was not altered in PARP-14 deficient macrophages. Consistent with the in vitro data, TF expression and TF activity, but not TNF alpha expression, were increased in Parp14(-/-) mice in vivo. Our study provides a novel mechanism for the posttranscriptional regulation of TF expression, indicating that this is selectively regulated by PARP-14. C1 [Iqbal, M. Bilal; Johns, Michael; Cao, Jun; Liu, Yu; Yu, Sheng-Chun; Hyde, Gareth D.; Haskard, Dorian O.] Univ London Imperial Coll Sci Technol & Med, Vasc Sci Sect, Natl Heart & Lung Inst, London W12 ONN, England. [Laffan, Michael A.; Gavins, Felicity N.; Woollard, Kevin J.] Imperial Coll London, Dept Med, London, England. [Marchese, Francesco P.; Dean, Jonathan L.] Univ Oxford, Div Rheumatol, Kennedy Inst, Oxford, England. [Cho, Sung Hoon; Boothby, Mark] Vanderbilt Univ, Dept Pathol Microbiol & Immunol, Nashville, TN 37235 USA. [Clark, Andrew R.] Univ Birmingham, Ctr Translat Inflammat Res, Birmingham, W Midlands, England. [Blackshear, Perry J.] NIEHS, Res Triangle Pk, NC 27709 USA. [Mackman, Nigel] Univ N Carolina, Dept Med, McAllister Heart Inst, Chapel Hill, NC USA. RP Haskard, DO (reprint author), Univ London Imperial Coll Sci Technol & Med, Hammersmith Hosp, Natl Heart & Lung Inst, Vasc Sci Sect, Du Cane Rd, London W12 ONN, England. EM d.haskard@imperial.ac.uk OI Woollard, Kevin/0000-0002-9839-5463; Clark, Andy/0000-0003-4996-8322 FU British Heart Foundation FX The authors gratefully acknowledge Deborah J. Stumpo (National Institute of Environmental Health Sciences) for help with the Ttp-/- mice. The work was funded by grants from the British Heart Foundation. NR 50 TC 14 Z9 14 U1 2 U2 12 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 2021 L ST NW, SUITE 900, WASHINGTON, DC 20036 USA SN 0006-4971 EI 1528-0020 J9 BLOOD JI Blood PD DEC 4 PY 2014 VL 124 IS 24 BP 3646 EP 3655 DI 10.1182/blood-2014-07-588046 PG 10 WC Hematology SC Hematology GA AY3DZ UT WOS:000347465900021 PM 25293769 ER PT J AU Cooks, T Harris, CC AF Cooks, Tomer Harris, Curtis C. TI p53 Mutations and Inflammation-Associated Cancer Are Linked through TNF Signaling SO MOLECULAR CELL LA English DT Editorial Material ID MUTANT P53; ACTIVATION C1 [Cooks, Tomer; Harris, Curtis C.] NCI, Human Carcinogenesis Lab, NIH, Bethesda, MD 20892 USA. RP Cooks, T (reprint author), NCI, Human Carcinogenesis Lab, NIH, Bldg 37, Bethesda, MD 20892 USA. EM tomer.cooks@nih.gov NR 10 TC 1 Z9 2 U1 1 U2 6 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 1097-2765 EI 1097-4164 J9 MOL CELL JI Mol. Cell PD DEC 4 PY 2014 VL 56 IS 5 BP 611 EP 612 DI 10.1016/j.molcel.2014.11.018 PG 2 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA AX0PE UT WOS:000346653300001 PM 25479634 ER PT J AU Duan, JB Shi, JX Fiorentino, A Leites, C Chen, XN Moy, W Chen, JC Alexandrov, BS Usheva, A He, DL Freda, J O'Brien, NL McQuillin, A Sanders, AR Gershon, ES DeLisi, LE Bishop, AR Gurling, HMD Pato, MT Levinson, DF Kendler, KS Pato, CN Gejman, PV AF Duan, Jubao Shi, Jianxin Fiorentino, Alessia Leites, Catherine Chen, Xiangning Moy, Winton Chen, Jingchun Alexandrov, Boian S. Usheva, Anny He, Deli Freda, Jessica O'Brien, Niamh L. McQuillin, Andrew Sanders, Alan R. Gershon, Elliot S. DeLisi, Lynn E. Bishop, Alan R. Gurling, Hugh M. D. Pato, Michele T. Levinson, Douglas F. Kendler, Kenneth S. Pato, Carlos N. Gejman, Pablo V. CA MGS GPC TI A Rare Functional Noncoding Variant at the GWAS-Implicated MIR137/MIR2682 Locus Might Confer Risk to Schizophrenia and Bipolar Disorder SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Article ID GENOME-WIDE ASSOCIATION; INFLAMMATORY-BOWEL-DISEASE; MACULAR DEGENERATION; COMMON VARIANTS; PSYCHIATRIC-DISORDERS; TRANSCRIPTION FACTOR; REGULATORY ELEMENTS; LOW-FREQUENCY; STEM-CELLS; MIR137 AB Schizophrenia (SZ) genome-wide association studies (GWASs) have identified common risk variants in >100 susceptibility loci; however, the contribution of rare variants at these loci remains largely unexplored. One of the strongly associated loci spans MIR137 (miR137) and M1R2682 (miR2682), two microRNA genes important for neuronal function. We sequenced -6.9 kb MIR137/MIR2682 and upstream regulatory sequences in 2,610 SZ cases and 2,611 controls of European ancestry. We identified 133 rare variants with minor allele frequency (MAF) <0.5%. The rare variant burden in promoters and enhancers, but not insulators, was associated with SZ (p = 0.021 for MAF < 0.5%, p = 0.003 for MAF < 0.1%). A rare enhancer SNP, 1:g.98515539A>T, presented exclusively in 11 SZ cases (nominal p = 4.8 x 10(-4) ). We further identified its risk allele Tin 2 of 2,434 additional SZ cases, 11 of 4,339 bipolar (BP) cases, and 3 of 3,572 SZ/BP study controls and 1,688 population controls; yielding combined p values of 0.0007, 0.0013, and 0.0001 for SZ, BP, and SZ/BP, respectively. The risk allele T of 1:g.98515539A>T reduced enhancer activity of its flanking sequence by >50% in human neuroblastoma cells, predicting lower expression of MIR137/MIR2682. Both empirical and computational analyses showed weaker transcription factor (YY1) binding by the risk allele. Chromatin conformation capture (3C) assay further indicated that 1:g.98515539A>T influenced MIR137/MIR2682, but not the nearby DPYD or LOC729987. Our results suggest that rare noncoding risk variants are associated with SZ and BP at MIR137/MIR2682 locus, with risk alleles decreasing MIR137/MIR2682 expression. C1 [Duan, Jubao; Leites, Catherine; Moy, Winton; He, Deli; Freda, Jessica; Sanders, Alan R.; Gejman, Pablo V.] NorthShore Univ HealthSyst, Dept Psychiat & Behav Sci, Ctr Psychiat Genet, Evanston, IL 60201 USA. [Duan, Jubao; Sanders, Alan R.; Gershon, Elliot S.; Gejman, Pablo V.] Univ Chicago, Dept Psychiat & Behav Neurosci, Chicago, IL 60637 USA. [Shi, Jianxin] NCI, Biostat Branch, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. [Fiorentino, Alessia; O'Brien, Niamh L.; McQuillin, Andrew; Gurling, Hugh M. D.] UCL, Mol Psychiat Lab, Div Psychiat, London WC1E 6JJ, England. [Chen, Xiangning; Chen, Jingchun; Kendler, Kenneth S.] Virginia Commonwealth Univ, Virginia Inst Psychiat & Behav Genet, Richmond, VA 23298 USA. [Alexandrov, Boian S.; Usheva, Anny] Harvard Univ, Sch Med, Boston, MA 02115 USA. [Alexandrov, Boian S.; Bishop, Alan R.] Los Alamos Natl Lab, Los Alamos, NM 87544 USA. [DeLisi, Lynn E.] Harvard Univ, Sch Med, VA Boston Healthcare Syst, Brockton, MA 02301 USA. [Pato, Michele T.; Pato, Carlos N.] Univ So Calif, Keck Sch Med, Dept Psychiat & Behav Sci, Los Angeles, CA 90033 USA. [Levinson, Douglas F.] Stanford Univ, Sch Med, Dept Psychiat & Behav Sci, Palo Alto, CA 94305 USA. RP Duan, JB (reprint author), NorthShore Univ HealthSyst, Dept Psychiat & Behav Sci, Ctr Psychiat Genet, Evanston, IL 60201 USA. EM jduan@uchicago.edu RI Macciardi, Fabio/N-3768-2014; McQuillin, Andrew/C-1623-2008; OI Macciardi, Fabio/0000-0003-0537-4266; McQuillin, Andrew/0000-0003-1567-2240; Nicolini, Humberto/0000-0003-2494-0067; Alexandrov, Boian/0000-0001-8636-4603 FU Wellcome Trust [WT091310]; NIH [R01MH067257, R01MH059588, R01MH059565, R01MH059587, R01MH060870, R01MH059566, R01MH059586, R01MH061675, R01MH060879, U01MH046276, U01MH079470]; MRC [G1000708]; National Nuclear Security Administration of the US Department of Energy; LANL, LDRD [20110516ECR]; National Institutes of Health (NIH) [R21MH102685]; NorthShore University HealthSystem Research Career Development Award; [R01MH059571]; [R01MH081800]; [U01MH079469]; [MH085548]; [MH085542] FX We thank the study participants of MGS, CNG, ICCSS, ISHDSF, UCL, GPC, NIME-BP collections. This study also makes use of whole-genome sequencing data (TwinsUK) generated by the UK10K Consortium. A full list of the investigators who contributed to the generation of the data is available from UK10K Project homepage. Wellcome Trust award WT091310 provided funding for UK10K. We also thank K. Fang and N. Park (Illinois Mathematics and Science Academy) for their technical help with the 3C experiment. This work was primarily supported by R01MH059571, R01MH081800, and U01MH079469 (to P.V.G.) and other NIH grants for MGS (R01MH067257 to N.G.B., R01MH059588 to B.J.M., R01MH059565 to R.F., R01MH059587 to F.A., R01MH060870 to W.F.B., R01MH059566 to D.W.B., R01MH059586 to J.M.S., R01MH061675 to D.F.L., R01MH060879 to C.R.C., U01MH046276 to C.R.C., and U01MH079470 to D.F.L). GPC was supported by MH085548 and MH085542 (to C.N.P and M.T.P). UCL genotyping was supported by MRC grant G1000708 (to H.M.D.G. and A.M.). The computational modeling of transcription factor binding at Los Alamos National Laboratory was carried out under the auspices of the National Nuclear Security Administration of the US Department of Energy and was supported by the LANL, LDRD, 20110516ECR grant (to B.S.A.). This work was also partially supported by National Institutes of Health (NIH) grant R21MH102685 and NorthShore University HealthSystem Research Career Development Award (to J.D.). NR 76 TC 17 Z9 17 U1 1 U2 21 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 0002-9297 EI 1537-6605 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD DEC 4 PY 2014 VL 95 IS 6 BP 744 EP 753 DI 10.1016/j.ajhg.2014.11.001 PG 10 WC Genetics & Heredity SC Genetics & Heredity GA AX0DH UT WOS:000346623100011 PM 25434007 ER PT J AU Yilmaz, B Portugal, S Tran, TM Gozzelino, R Ramos, S Gomes, J Regalado, A Cowan, PJ d'Apice, AJF Chong, AS Doumbo, OK Traore, B Crompton, PD Silveira, H Soares, MP AF Yilmaz, Bahtiyar Portugal, Silvia Tran, Tuan M. Gozzelino, Raffaella Ramos, Susana Gomes, Joana Regalado, Ana Cowan, Peter J. d'Apice, Anthony J. F. Chong, Anita S. Doumbo, Ogobara K. Traore, Boubacar Crompton, Peter D. Silveira, Henrique Soares, Miguel P. TI Gut Microbiota Elicits a Protective Immune Response against Malaria Transmission SO CELL LA English DT Article ID EXPERIMENTAL CEREBRAL MALARIA; ALPHA-GALACTOSYL IGG; ANTI-GAL ANTIBODIES; FC-GAMMA RECEPTORS; SWITCH RECOMBINATION; HYPERACUTE REJECTION; CLINICAL-RELEVANCE; HUMAN SERUM; CELLS; INFECTION AB Glycosylation processes are under high natural selection pressure, presumably because these can modulate resistance to infection. Here, we asked whether inactivation of the UDP-galactose: beta-galac-toside- alpha-1-3-galactosyltransferase (alpha 1,3GT) gene, which ablated the expression of the Gal alpha 1-3Gal beta 1-4GlcNAc- R(alpha-gal) glycan and allowed for the production of anti-alpha-gal antibodies (Abs) in humans, confers protection against Plasmodium spp. infection, the causative agent of malaria and a major driving force in human evolution. We demonstrate that both Plasmodium spp. and the human gut pathobiont E. coli O86: B7 express alpha-gal and that anti-alpha-gal Abs are associated with protection against malaria transmission in humans as well as in alpha 1,3GT-deficient mice, which produce protective anti-alpha-gal Abs when colonized by E. coli O86:B7. Anti-alpha-gal Abs target Plasmodium sporozoites for complement-mediated cytotoxicity in the skin, immediately after inoculation by Anopheles mosquitoes. Vaccination against a-gal confers sterile protection against malaria in mice, suggesting that a similar approach may reduce malaria transmission in humans. C1 [Yilmaz, Bahtiyar; Gozzelino, Raffaella; Ramos, Susana; Gomes, Joana; Regalado, Ana; Soares, Miguel P.] Inst Gulbenkian Ciencias, P-2780156 Oeiras, Portugal. [Portugal, Silvia; Tran, Tuan M.; Crompton, Peter D.] NIAID, Immunogenet Lab, NIH, Rockville, MD 20852 USA. [Gomes, Joana; Silveira, Henrique] Univ Nova Lisboa, Ctr Malaria & Outras Doencas Trop, Inst Higiene & Med Trop, P-1349008 Lisbon, Portugal. [Cowan, Peter J.; d'Apice, Anthony J. F.] St Vincents Hosp, Immunol Res Ctr, Melbourne, Vic 3065, Australia. [Cowan, Peter J.; d'Apice, Anthony J. F.] Univ Melbourne, Dept Med, Parkville, Vic 2900, Australia. [Chong, Anita S.] Univ Chicago, Sect Transplantat, Dept Surg, Chicago, IL 60637 USA. [Doumbo, Ogobara K.; Traore, Boubacar] Univ Sci Tech & Technol Bamako, Mali Int Ctr Excellence Res, Bamako 1805, Mali. RP Soares, MP (reprint author), Inst Gulbenkian Ciencias, Rua Quinta Grande 6, P-2780156 Oeiras, Portugal. EM mpsoares@igc.gulbenkian.pt RI Ramos, Susana/M-2064-2014; Silveira, Henrique/G-2229-2011; Crompton, Peter/N-1130-2016; Gozzelino, Raffaella/E-8147-2017; OI Ramos, Susana/0000-0001-6356-1065; Silveira, Henrique/0000-0002-7939-772X; Gozzelino, Raffaella/0000-0002-1195-8527; Soares, Miguel/0000-0002-9314-4833; Yilmaz, Bahtiyar/0000-0003-1888-9226 FU Bill and Melinda Gates Foundation [OPP1024563]; Fundacao para a Ciencia e Tecnologia [RECI-IMI-IMU-0038-2012]; European Research Council [ERC-2011-AdG 294709-DAMAGECONTROL]; Fundacao para a Ciencia e a Tecnologia within the PhDProgram of Integrative Biomedical Science of the Instituto Gulbenkian de Ciencia [SFRH/BD/51176/2010]; Division of Intramural Research, National Institute of Allergy and Infectious Diseases; NIH; EMMA; EU FX The authors thank the Inflammation Group (IGC) for insightful discussions and review of the manuscript, Sofia Rebelo and Silvia Cardoso for mouse breeding and genotyping, Pedro Almada and Nuno Pimpao Martins (IGC Imaging Facility) for technical support, Karen Berman de Ruiz and Joana Bom (IGC Animal Facility) for germ-free breeding, Joana Tavares, Rogerio Amino, and Robert Menard (Institute Pasteur) for technical support, Alekos Athanasiadis and Jocelyne Demengeot for insightful discussions, Pascal Gagneaux (University of California San Diego), and Daniel Mucida (Rockefeller University) for critical review of the initial version of the manuscript. Financial support from the Bill and Melinda Gates Foundation (OPP1024563), Fundacao para a Ciencia e Tecnologia (RECI-IMI-IMU-0038-2012), and European Research Council (ERC-2011-AdG 294709-DAMAGECONTROL) (to M.P.S.) and Fundacao para a Ciencia e a Tecnologia (SFRH/BD/51176/2010) within the PhDProgram of Integrative Biomedical Science of the Instituto Gulbenkian de Ciencia (to B.Y.) is gratefully acknowledged. The Division of Intramural Research, National Institute of Allergy and Infectious Diseases, and NIH supported the Mali cohort study. Mouse axenization was supported by the EMMA, EU FP7 Capacities Specific Program. NR 61 TC 41 Z9 47 U1 8 U2 51 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 0092-8674 EI 1097-4172 J9 CELL JI Cell PD DEC 4 PY 2014 VL 159 IS 6 BP 1277 EP 1289 DI 10.1016/j.cell.2014.10.053 PG 13 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA AX0PA UT WOS:000346652900008 PM 25480293 ER PT J AU Freund, A Zhong, FL Venteicher, AS Meng, ZJ Veenstra, TD Frydman, J Artandi, SE AF Freund, Adam Zhong, Franklin L. Venteicher, Andrew S. Meng, Zhaojing Veenstra, Timothy D. Frydman, Judith Artandi, Steven E. TI Proteostatic Control of Telomerase Function through TRiC-Mediated Folding of TCAB1 SO CELL LA English DT Article ID TERT PROMOTER MUTATIONS; DYSKERATOSIS-CONGENITA; CYTOSOLIC CHAPERONIN; CAJAL BODIES; MOLECULAR CHAPERONES; CELLS; RNA; RECRUITMENT; HOLOENZYME; PROTEINS AB Telomere maintenance by telomerase is impaired in the stem cell disease dyskeratosis congenita and during human aging. Telomerase depends upon a complex pathway for enzyme assembly, localization in Cajal bodies, and association with telomeres. Here, we identify the chaperonin CCT/TRiC as a critical regulator of telomerase trafficking using a high-content genome-wide siRNA screen in human cells for factors required for Cajal body localization. We find that TRiC is required for folding the telomerase cofactor TCAB1, which controls trafficking of telomerase and small Cajal body RNAs (scaRNAs). Depletion of TRiC causes loss of TCAB1 protein, mislocalization of telomerase and scaRNAs to nucleoli, and failure of telomere elongation. DC patient-derived mutations in TCAB1 impair folding by TRiC, disrupting telomerase function and leading to severe disease. Our findings establish a critical role for TRiC-mediated protein folding in the telomerase pathway and link proteostasis, telomere maintenance, and human disease. C1 [Freund, Adam; Venteicher, Andrew S.; Artandi, Steven E.] Stanford Univ, Dept Med, Sch Med, Stanford, CA 94305 USA. [Zhong, Franklin L.; Artandi, Steven E.] Stanford Univ, Canc Biol Program, Sch Med, Stanford, CA 94305 USA. [Meng, Zhaojing; Veenstra, Timothy D.] Sci Applicat Int Corp Frederick, Natl Canc Inst Frederick, Lab Prote & Analyt Technol, Frederick, MD 21702 USA. [Frydman, Judith] Stanford Univ, Dept Biol, Stanford, CA 94305 USA. [Artandi, Steven E.] Stanford Univ, Dept Biochem, Sch Med, Stanford, CA 94305 USA. RP Artandi, SE (reprint author), Stanford Univ, Dept Med, Sch Med, Stanford, CA 94305 USA. EM sartandi@stanford.edu FU NIH NCRR Instrumentation grant [S10RR026338]; Stanford Cancer Biology Training Program [T32 CA09302]; Jane Coffin Childs Memorial Fund for Medical Research; Agency for Science, Technology, and Research (A*STAR), Singapore; NIH [AG033747, CA125453, CA111691, AG036695]; Glenn Foundation for Medical Research FX We thank members of the Artandi and Frydman labs for helpful discussions and advice. We thank David Solow-Cordero in the Stanford High-Throughput Bioscience Center, with support from NIH NCRR Instrumentation grant S10RR026338. We are grateful to Anthony Tomlinson for generously providing purified bovine TRiC and to Sharon Savage for supplying DC patient lymphoblasts. A.F. was supported by Stanford Cancer Biology Training Program (T32 CA09302) and by a postdoctoral fellowship from the Jane Coffin Childs Memorial Fund for Medical Research. F.L.Z. was supported by a fellowship from the Agency for Science, Technology, and Research (A*STAR), Singapore. This work was supported by NIH grants AG033747, CA125453, CA111691, and AG036695 and by the Glenn Foundation for Medical Research. NR 49 TC 16 Z9 17 U1 2 U2 26 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 0092-8674 EI 1097-4172 J9 CELL JI Cell PD DEC 4 PY 2014 VL 159 IS 6 BP 1389 EP 1403 DI 10.1016/j.cell.2014.10.059 PG 15 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA AX0PA UT WOS:000346652900017 PM 25467444 ER PT J AU Lee, YJ Mou, YS Klimanis, D Bernstock, JD Hallenbeck, J AF Lee, Yang-ja Mou, Yougshan Klimanis, Dace Bernstock, Joshua D. Hallenbeck, Johnm. TI Global SUMOylation is a molecular mechanism underlying hypothermia-induced ischemic tolerance SO FRONTIERS IN CELLULAR NEUROSCIENCE LA English DT Article DE Hypothermia; SUMOylation; pMCAO; Neuroprotection; Ubc9 ID FOCAL CEREBRAL-ISCHEMIA; STROKE THERAPY; PROTEIN SUMOYLATION; SUMO; MICE; CONJUGATION; BRAIN; CELLS; INDUCTION; NEURONS AB The molecular mechanisms underlying hypothermic neuroprotection have yet to be fully elucidated. Herein we demonstrate that global SUMOylation, a form of post-translational modification with the Small Ubiquitin-like MOdifer, participates in the multimodal molecular induction of hypothermia-induced ischemic tolerance. Mild (32 degrees C) to moderate (28 degrees C) hypothermic treatment(s) during OGD (oxygen-glucose-deprivation) or ROG (restoration of oxygen/glucose) increased global SUMO-conjugation levels and protected cells (both SHSY5Y and E18 rat cortical neurons) from OGD and ROG-induced cell death. Hypothermic exposure either before or after permanent middle cerebral artery occlusion (pMCAO) surgery in wild type mice increased global SUMO-conjugation levels in the brain and in so doing protected these animals from pMCAO-induced ischemic damage. Of note, hypothermic exposure did not provide an additional increase in protection from pMCAO-induced ischemic brain damage in Ubc9 transgenic (Ubc9 Tg) mice, which overexpress the sole E2 SUMO conjugating enzyme and thereby display elevated basal levels of global SUMOylation under normothermic conditions. Such evidence suggests that increases in global SUMOylation are critical and may account for a substantial part of the observed increase in cellular tolerance to brain ischemia caused via hypothermia. Keywords: Hypothermia. C1 [Lee, Yang-ja; Mou, Yougshan; Klimanis, Dace; Bernstock, Joshua D.; Hallenbeck, Johnm.] NINDS, Stroke Branch, NIH, Bethesda, MD 20892 USA. RP Hallenbeck, J (reprint author), NINDS, Stroke Branch, NIH, Bldg10 Rm5B02 MSC 1401,10 Ctr Dr, Bethesda, MD 20892 USA. EM hallenbj@ninds.nih.gov FU Intramural Research Program of the NINDS/NIH FX This research was supported by the Intramural Research Program of the NINDS/NIH. The authors wish to thank Dr. Dragan Maric (NINDS/NIH) for help with the FACS analysis. NR 45 TC 6 Z9 6 U1 2 U2 5 PU FRONTIERS RESEARCH FOUNDATION PI LAUSANNE PA PO BOX 110, LAUSANNE, 1015, SWITZERLAND SN 1662-5102 J9 FRONT CELL NEUROSCI JI Front. Cell. Neurosci. PD DEC 4 PY 2014 VL 8 AR 416 DI 10.3389/fncel.2014.00416 PG 9 WC Neurosciences SC Neurosciences & Neurology GA AX2NZ UT WOS:000346782200001 PM 25538566 ER PT J AU Bond, MR Ghosh, SK Wang, P Hanover, JA AF Bond, Michelle R. Ghosh, Salil K. Wang, Peng Hanover, John A. TI Conserved Nutrient Sensor O-GlcNAc Transferase Is Integral to C. elegans Pathogen-Specific Immunity SO PLOS ONE LA English DT Article ID CAENORHABDITIS-ELEGANS; BETA-CATENIN; SIGNALING PATHWAY; INNATE IMMUNITY; STRESS-RESPONSE; LIFE-SPAN; MODEL; ACTIVATION; GLYCOSYLATION; GLCNACYLATION AB Discriminating pathogenic bacteria from bacteria used as a food source is key to Caenorhabidits elegans immunity. Using mutants defective in the enzymes of O-linked N-acetylglucosamine (O-GlcNAc) cycling, we examined the role of this nutrient-sensing pathway in the C. elegans innate immune response. Genetic analysis showed that deletion of O-GlcNAc transferase (ogt-1) yielded animals hypersensitive to the human pathogen S. aureus but not to P. aeruginosa. Genetic interaction studies revealed that nutrient-responsive OGT-1 acts through the conserved beta-catenin (BAR-1) pathway and in concert with p38 MAPK (PMK-1) to modulate the immune response to S. aureus. Moreover, whole genome transcriptional profiling revealed that O-GlcNAc cycling mutants exhibited deregulation of unique stress-and immune-responsive genes. The participation of nutrient sensor OGT-1 in an immunity module evolutionarily conserved from C. elegans to humans reveals an unexplored nexus between nutrient availability and a pathogen-specific immune response. C1 [Bond, Michelle R.; Hanover, John A.] NIDDK, NIH, Bethesda, MD 20892 USA. [Ghosh, Salil K.] US FDA, Ctr Biol Evaluat & Res, Silver Spring, MD USA. [Wang, Peng] Medstar Georgetown Univ Hosp, Dept Pathol, Washington, DC USA. RP Hanover, JA (reprint author), NIDDK, NIH, Bethesda, MD 20892 USA. EM jah@helix.nih.gov FU NIDDK intramural funds (NIH) FX This work was supported by NIDDK intramural funds (NIH). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 61 TC 5 Z9 5 U1 4 U2 9 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA SN 1932-6203 J9 PLOS ONE JI PLoS One PD DEC 4 PY 2014 VL 9 IS 12 AR e113231 DI 10.1371/journal.pone.0113231 PG 26 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA AW6MB UT WOS:000346382500079 PM 25474640 ER PT J AU Cardone, M Dzutsev, AK Li, HC Riteau, N Gerosa, F Shenderov, K Winkler-Pickett, R Provezza, L Riboldi, E Leighty, RM Orr, SJ Steinhagen, F Wewers, MD Sher, A Anderson, SK Goldszmid, R McVicar, DW Lyakh, L Trinchieri, G AF Cardone, Marco Dzutsev, Amiran K. Li, Hongchuan Riteau, Nicolas Gerosa, Franca Shenderov, Kevin Winkler-Pickett, Robin Provezza, Lisa Riboldi, Elena Leighty, Robert M. Orr, Selinda J. Steinhagen, Folkert Wewers, Mark D. Sher, Alan Anderson, Stephen K. Goldszmid, Romina McVicar, Daniel W. Lyakh, Lyudmila Trinchieri, Giorgio TI Interleukin-1 and Interferon-gamma Orchestrate beta-Glucan-Activated Human Dendritic Cell Programming via I kappa B-zeta Modulation SO PLOS ONE LA English DT Article ID INDUCIBLE NUCLEAR-PROTEIN; T-HELPER-CELLS; NLRP3 INFLAMMASOME; HUMAN MACROPHAGES; CANDIDA-ALBICANS; HOST-DEFENSE; IFN-GAMMA; DIFFERENTIAL REQUIREMENT; IL-1-BETA PRODUCTION; RECEPTOR DECTIN-1 AB Recognition of microbial components via innate receptors including the C-type lectin receptor Dectin-1, together with the inflammatory environment, programs dendritic cells (DCs) to orchestrate the magnitude and type of adaptive immune responses. The exposure to beta-glucan, a known Dectin-1 agonist and component of fungi, yeasts, and certain immune support supplements, activates DCs to induce T helper (Th)17 cells that are essential against fungal pathogens and extracellular bacteria but may trigger inflammatory pathology or autoimmune diseases. However, the exact mechanisms of DC programming by beta-glucan have not yet been fully elucidated. Using a gene expression/perturbation approach, we demonstrate that in human DCs beta-glucan transcriptionally activates via an interleukin (IL)-1- and inflammasome-mediated positive feedback late-induced genes that bridge innate and adaptive immunity. We report that in addition to its known ability to directly prime T cells toward the Th17 lineage, IL-1 by promoting the transcriptional cofactor inhibitor of kappa B-zeta (I kappa B-zeta) also programs beta-glucan-exposed DCs to express cell adhesion and migration mediators, antimicrobial molecules, and Th17-polarizing factors. Interferon (IFN)-gamma interferes with the IL-1/I kappa B-zeta axis in beta-glucan-activated DCs and promotes T cell- mediated immune responses with increased release of IFN-gamma and IL-22, and diminished production of IL-17. Thus, our results identify IL-1 and IFN-gamma as regulators of DC programming by beta-glucan. These molecular networks provide new insights into the regulation of the Th17 response as well as new targets for the modulation of immune responses to beta-glucancontaining microorganisms. C1 [Cardone, Marco; Dzutsev, Amiran K.; Li, Hongchuan; Winkler-Pickett, Robin; Riboldi, Elena; Orr, Selinda J.; Steinhagen, Folkert; Anderson, Stephen K.; Goldszmid, Romina; McVicar, Daniel W.; Lyakh, Lyudmila; Trinchieri, Giorgio] NCI, Canc & Inflammat Program, Ctr Canc Res, NIH, Frederick, MD 21701 USA. [Dzutsev, Amiran K.; Li, Hongchuan; Anderson, Stephen K.] Leidos Biomed Res Inc, Frederick Natl Lab Canc Res, Basic Sci Program, Frederick, MD USA. [Riteau, Nicolas; Shenderov, Kevin; Sher, Alan] NIAID, Immunobiol Sect, Parasit Dis Lab, NIH, Bethesda, MD 20892 USA. [Gerosa, Franca; Provezza, Lisa] Univ Verona, Dept Pathol, I-37100 Verona, Italy. [Leighty, Robert M.] Data Management Serv Inc, Frederick Natl Lab Canc Res, Frederick, MD USA. [Wewers, Mark D.] Ohio State Univ, Davis Heart & Lung Res Inst, Columbus, OH 43210 USA. [Trinchieri, Giorgio] Trans NIH Ctr Human Immunol, Bethesda, MD USA. RP Trinchieri, G (reprint author), NCI, Canc & Inflammat Program, Ctr Canc Res, NIH, Frederick, MD 21701 USA. EM trinchig@mail.nih.gov RI McVicar, Daniel/G-1970-2015 FU Intramural Research Program of the National Cancer Institute, National Institutes of Health [HHSN261200800001E] FX This research was fully supported by the Intramural Research Program of the National Cancer Institute, National Institutes of Health, in part through the contract HHSN261200800001E to the Frederick National Laboratory for Cancer Research. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 64 TC 6 Z9 6 U1 0 U2 7 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA SN 1932-6203 J9 PLOS ONE JI PLoS One PD DEC 4 PY 2014 VL 9 IS 12 AR e114516 DI 10.1371/journal.pone.0114516 PG 29 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA AW6MB UT WOS:000346382500041 PM 25474109 ER PT J AU Smith, PK Puskas, JD Ascheim, DD Voisine, P Gelijns, AC Moskowitz, AJ Hung, JW Parides, MK Ailawadi, G Perrault, LP Acker, MA Argenziano, M Thourani, V Gammie, JS Miller, MA Page, P Overbey, JR Bagiella, E Dagenais, F Blackstone, EH Kron, IL Rose, EA Moquete, EG Jeffries, N Gardner, TJ O'Gara, PT Alexander, JH Michler, RE AF Smith, P. K. Puskas, J. D. Ascheim, D. D. Voisine, P. Gelijns, A. C. Moskowitz, A. J. Hung, J. W. Parides, M. K. Ailawadi, G. Perrault, L. P. Acker, M. A. Argenziano, M. Thourani, V. Gammie, J. S. Miller, M. A. Page, P. Overbey, J. R. Bagiella, E. Dagenais, F. Blackstone, E. H. Kron, I. L. Rose, E. A. Moquete, E. G. Jeffries, N. Gardner, T. J. O'Gara, P. T. Alexander, J. H. Michler, R. E. CA Cardiothoracic Surg Trials Network TI Surgical Treatment of Moderate Ischemic Mitral Regurgitation SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Article ID MYOCARDIAL-INFARCTION; HEART-FAILURE; THORACIC SURGEONS; CLINICAL-TRIALS; SURVIVAL; REVASCULARIZATION; ECHOCARDIOGRAPHY; ASSOCIATION; DETERMINANT; MECHANISM AB BACKGROUND Ischemic mitral regurgitation is associated with increased mortality and morbidity. For surgical patients with moderate regurgitation, the benefits of adding mitralvalve repair to coronary-artery bypass grafting (CABG) are uncertain. METHODS We randomly assigned 301 patients with moderate ischemic mitral regurgitation to CABG alone or CABG plus mitral-valve repair (combined procedure). The primary end point was the left ventricular end-systolic volume index (LVESVI), a measure of left ventricular remodeling, at 1 year. This end point was assessed with the use of a Wilcoxon rank-sum test in which deaths were categorized as the lowest LVESVI rank. RESULTS At 1 year, the mean LVESVI among surviving patients was 46.1+/-22.4 ml per square meter of body-surface area in the CABG-alone group and 49.6+/-31.5 ml per square meter in the combined-procedure group (mean change from baseline, -9.4 and -9.3 ml per square meter, respectively). The rate of death was 6.7% in the combined-procedure group and 7.3% in the CABG-alone group (hazard ratio with mitral-valve repair, 0.90; 95% confidence interval, 0.38 to 2.12; P = 0.81). The rank-based assessment of LVESVI at 1 year (incorporating deaths) showed no significant between-group difference (z score, 0.50; P = 0.61). The addition of mitral-valve repair was associated with a longer bypass time (P<0.001), a longer hospital stay after surgery (P = 0.002), and more neurologic events (P = 0.03). Moderate or severe mitral regurgitation was less common in the combined-procedure group than in the CABG-alone group (11.2% vs. 31.0%, P<0.001). There were no significant between-group differences in major adverse cardiac or cerebrovascular events, deaths, readmissions, functional status, or quality of life at 1 year. CONCLUSIONS In patients with moderate ischemic mitral regurgitation, the addition of mitral-valve repair to CABG did not result in a higher degree of left ventricular reverse remodeling. Mitral-valve repair was associated with a reduced prevalence of moderate or severe mitral regurgitation but an increased number of untoward events. Thus, at 1 year, this trial did not show a clinically meaningful advantage of adding mitral-valve repair to CABG. Longer-term follow-up may determine whether the lower prevalence of mitral regurgitation translates into a net clinical benefit. C1 [Smith, P. K.] Duke Univ, Med Ctr, Dept Surg, Div Cardiovasc & Thorac Surg, Durham, NC 27710 USA. [Alexander, J. H.] Duke Univ, Med Ctr, Dept Med, Div Cardiol, Durham, NC 27710 USA. [Puskas, J. D.; Rose, E. A.] Icahn Sch Med Mt Sinai, Mt Sinai Hlth Syst, Dept Cardiac Surg, New York, NY 10029 USA. [Ascheim, D. D.; Gelijns, A. C.; Moskowitz, A. J.; Parides, M. K.; Overbey, J. R.; Bagiella, E.; Moquete, E. G.] Icahn Sch Med Mt Sinai, Dept Populat Hlth Sci & Policy, Int Ctr Hlth Outcomes & Innovat Res, New York, NY 10029 USA. [Argenziano, M.] Columbia Univ, Coll Phys & Surg, Dept Surg, Dept Cardiothorac Surg, New York, NY USA. [Michler, R. E.] Albert Einstein Coll Med, Monash Med Ctr, Dept Cardiothorac & Vasc Surg, New York, NY USA. [Voisine, P.; Dagenais, F.] Hop Laval, Inst Univ Cardiol & Pneumol Quebec, Quebec City, PQ, Canada. [Perrault, L. P.] Univ Montreal, Montreal Heart Inst, Montreal, PQ, Canada. [Page, P.] Hop Sacre Coeur, Dept Surg, Montreal, PQ H4J 1C5, Canada. [Hung, J. W.] Massachusetts Gen Hosp, Echocardiog Core Lab, Boston, MA 02114 USA. [O'Gara, P. T.] Brigham & Womens Hosp, Div Cardiovasc, Boston, MA 02115 USA. [Ailawadi, G.; Kron, I. L.] Univ Virginia, Sch Med, Div Thorac & Cardiovasc Surg, Charlottesville, VA 22908 USA. [Acker, M. A.] Univ Penn, Sch Med, Dept Surg, Div Cardiovasc Surg, Philadelphia, PA 19104 USA. [Thourani, V.] Emory Univ, Sch Med, Div Cardiothorac Surg, Clin Res Unit, Atlanta, GA 30322 USA. [Gammie, J. S.] Univ Maryland, Baltimore, MD 21201 USA. [Miller, M. A.] NHLBI, Div Cardiovasc Sci, Bethesda, MD 20892 USA. [Jeffries, N.] NHLBI, Off Biostat Res, Bethesda, MD 20892 USA. [Blackstone, E. H.] Cleveland Clin Fdn, Dept Thorac & Cardiovasc Surg, Cleveland, OH USA. [Gardner, T. J.] Christiana Care Hlth Syst, Ctr Heart & Vasc Hlth, Newark, DE USA. RP Gelijns, AC (reprint author), Icahn Sch Med Mt Sinai, Dept Populat Hlth Sci & Policy, 1 Gustave L Levy Pl,Box 1077, New York, NY 10029 USA. EM annetine.gelijns@mssm.edu RI Stevens, Louis-Mathieu/E-6453-2016; OI Stevens, Louis-Mathieu/0000-0003-3372-3419; Moskowitz, Alan/0000-0002-4412-9450; Browndyke, Jeffrey/0000-0002-8573-7073 FU National Heart, Lung, and Blood Institute [U01 HL088942]; National Institute of Neurological Disorders and Stroke; Canadian Institutes of Health Research; Thoratec and HeartWare; Edwards Lifesciences; St. Jude Medical; Sorin Medical FX Supported by a cooperative agreement (U01 HL088942) with the National Heart, Lung, and Blood Institute, including funding by the National Institute of Neurological Disorders and Stroke and the Canadian Institutes of Health Research.; Dr. Acker reports receiving consulting fees from Thoratec and HeartWare. Dr. Gelijns reports holding equity in MERS International. Dr. Thourani reports receiving grant support from Edwards Lifesciences, St. Jude Medical, and Sorin Medical. No other potential conflict of interest relevant to this article was reported. NR 42 TC 93 Z9 96 U1 0 U2 11 PU MASSACHUSETTS MEDICAL SOC PI WALTHAM PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA SN 0028-4793 EI 1533-4406 J9 NEW ENGL J MED JI N. Engl. J. Med. PD DEC 4 PY 2014 VL 371 IS 23 BP 2178 EP 2188 DI 10.1056/NEJMoa1410490 PG 11 WC Medicine, General & Internal SC General & Internal Medicine GA AW0IY UT WOS:000345976700006 PM 25405390 ER PT J AU Blair, RJR Leibenluft, E Pine, DS AF Blair, R. James R. Leibenluft, Ellen Pine, Daniel S. TI Conduct Disorder and Callous-Unemotional Traits in Youth SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Review ID DISRUPTIVE BEHAVIOR DISORDERS; ATTENTION-DEFICIT/HYPERACTIVITY DISORDER; OPPOSITIONAL DEFIANT DISORDER; ANTISOCIAL-BEHAVIOR; AMYGDALA RESPONSE; PSYCHOPATHIC TRAITS; DEVELOPMENTAL PATHWAYS; REWARD ANTICIPATION; PREFRONTAL CORTEX; MODERATING ROLE C1 [Blair, R. James R.; Leibenluft, Ellen; Pine, Daniel S.] NIMH, Hlth Intramural Res Program, NIH, Bethesda, MD 20892 USA. RP Blair, RJR (reprint author), NIMH, NIH, 10 Ctr Dr,Rm 4C104, Bethesda, MD 20892 USA. EM jamesblair@mail.nih.gov NR 75 TC 34 Z9 35 U1 13 U2 76 PU MASSACHUSETTS MEDICAL SOC PI WALTHAM PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA SN 0028-4793 EI 1533-4406 J9 NEW ENGL J MED JI N. Engl. J. Med. PD DEC 4 PY 2014 VL 371 IS 23 BP 2207 EP 2216 DI 10.1056/NEJMra1315612 PG 10 WC Medicine, General & Internal SC General & Internal Medicine GA AW0IY UT WOS:000345976700009 PM 25470696 ER PT J AU Bredeson, S Papaconstantinou, J Deford, JH Kechichian, T Syed, TA Saade, GR Menon, R AF Bredeson, Sarah Papaconstantinou, John Deford, James H. Kechichian, Talar Syed, Tariq A. Saade, George R. Menon, Ramkumar TI HMGB1 Promotes a p38MAPK Associated Non-Infectious Inflammatory Response Pathway in Human Fetal Membranes SO PLOS ONE LA English DT Article ID ACTIVATED PROTEIN-KINASE; GROUP BOX PROTEIN-1; PRETERM BIRTH; ALARMIN HMGB1; IN-VITRO; CYTOKINE; DNA; EXPRESSION; PHOSPHORYLATION; CELLS AB Objective: Spontaneous preterm birth (PTB) and preterm prelabor rupture of membranes (pPROM) are major pregnancy complications often associated with a fetal inflammatory response. Biomolecular markers of this fetal inflammatory response to both infectious and non-infectious risk factors and their contribution to PTB and pPROM mechanism are still unclear. This study examined fetal membrane production, activation and mechanistic properties of high mobility group box 1 (HMGB1) as a contributor of the non-infectious fetal inflammatory response. Materials and Methods: HMGB1 transcripts and active HMGB1 were profiled in fetal membranes and amniotic fluids collected from PTB and normal term birth. In vitro, normal term not in labor fetal membranes were exposed to lipopolysaccharide (LPS) and water soluble cigarette smoke extract (CSE). HMGB1-transcripts and its protein concentrations were documented by RT-PCR and ELISA. Recombinant HMGB1 treated membranes and media were subjected to RT-PCR for HMGB1 receptors, mitogen activated protein kinase pathway analysis, cytokine levels, and Western blot for p38MAPK. Results: HMGB1 expression and its active forms were higher in PTB and pPROM than normal term membranes and amniotic fluid samples. Both LPS and CSE enhanced HMGB1 expression and release in vitro. Fetal membrane exposure to HMGB1 resulted in increased expression of TLR2 and 4 and dose-dependent activation of p38MAPK-mediated inflammation. Conclusions: HMGB1 increase by fetal membrane cells in response to either oxidative stress or infection can provide a positive feedback loop generating noninfectious inflammatory activation. Activation of p38MAPK by HMGB1 promotes development of the senescence phenotype and senescence associated sterile inflammation. HMGB1 activity is an important regulator of the fetal inflammatory response regardless of infection. C1 [Bredeson, Sarah; Kechichian, Talar; Syed, Tariq A.; Saade, George R.; Menon, Ramkumar] Univ Texas Med Branch, Dept Obstet & Gynecol, Div Maternal Fetal Med & Perinatal Res, Galveston, TX 77555 USA. [Papaconstantinou, John; Deford, James H.] Univ Texas Med Branch, Dept Biochem & Mol Biol, NHLBI Prote Ctr Airway Inflammat, Galveston, TX 77555 USA. [Papaconstantinou, John; Deford, James H.] Univ Texas Med Branch, UTMB Biomol Resource Facil, Galveston, TX 77555 USA. RP Menon, R (reprint author), Univ Texas Med Branch, Dept Obstet & Gynecol, Div Maternal Fetal Med & Perinatal Res, Galveston, TX 77555 USA. EM ra2menon@utmb.edu FU dept of OB&GYN at The University of Texas Medical Branch at Galveston, Texas United States of America FX Funding: The study is conducted using developmental funds provided to Dr. R. Menon by the dept of OB&GYN at The University of Texas Medical Branch at Galveston, Texas United States of America. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 46 TC 24 Z9 28 U1 0 U2 4 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA SN 1932-6203 J9 PLOS ONE JI PLoS One PD DEC 3 PY 2014 VL 9 IS 12 AR e113799 DI 10.1371/journal.pone.0113799 PG 18 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA CA7WS UT WOS:000349128700047 PM 25469638 ER PT J AU Wang, SL Sun, LC Fang, JW AF Wang, Shu-Lin Sun, Liuchao Fang, Jianwen TI Molecular cancer classification using a meta-sample-based regularized robust coding method SO BMC BIOINFORMATICS LA English DT Article; Proceedings Paper CT 9th International Conference on Intelligent Computing (ICIC) CY JUL 28-31, 2013 CL Nanning, PEOPLES R CHINA SP Tongji Univ, Guangxi Univ Nationalities, IEEE Computat Intelligence Soc, Int Neural Network Soc, Natl Sci Fdn China ID GENE-EXPRESSION DATA; INDEPENDENT COMPONENT ANALYSIS; TUMOR CLASSIFICATION; SPARSE REPRESENTATION; FACE RECOGNITION; PREDICTION; SELECTION; REDUCTION; DISCOVERY; LEUKEMIA AB Motivation: Previous studies have demonstrated that machine learning based molecular cancer classification using gene expression profiling (GEP) data is promising for the clinic diagnosis and treatment of cancer. Novel classification methods with high efficiency and prediction accuracy are still needed to deal with high dimensionality and small sample size of typical GEP data. Recently the sparse representation (SR) method has been successfully applied to the cancer classification. Nevertheless, its efficiency needs to be improved when analyzing large-scale GEP data. Results: In this paper we present the meta-sample-based regularized robust coding classification (MRRCC), a novel effective cancer classification technique that combines the idea of meta-sample-based cluster method with regularized robust coding (RRC) method. It assumes that the coding residual and the coding coefficient are respectively independent and identically distributed. Similar to meta-sample-based SR classification (MSRC), MRRCC extracts a set of meta-samples from the training samples, and then encodes a testing sample as the sparse linear combination of these meta-samples. The representation fidelity is measured by the l(2)-norm or l(1)-norm of the coding residual. Conclusions: Extensive experiments on publicly available GEP datasets demonstrate that the proposed method is more efficient while its prediction accuracy is equivalent to existing MSRC-based methods and better than other state-of-the-art dimension reduction based methods. C1 [Wang, Shu-Lin; Sun, Liuchao] Hunan Univ, Coll Comp Sci & Elect Engn, Changsha 410082, Hunan, Peoples R China. [Fang, Jianwen] NCI, Div Canc Treatment & Diag, Biometr Res Branch, Rockville, MD 20850 USA. [Wang, Shu-Lin; Fang, Jianwen] Univ Kansas, Appl Bioinformat Lab, Lawrence, KS 66045 USA. RP Wang, SL (reprint author), Hunan Univ, Coll Comp Sci & Elect Engn, Changsha 410082, Hunan, Peoples R China. EM smartforesting@gmail.com; jianwen.fang@nih.gov FU NIA NIH HHS [P01 AG12993] NR 35 TC 0 Z9 0 U1 3 U2 14 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1471-2105 J9 BMC BIOINFORMATICS JI BMC Bioinformatics PD DEC 3 PY 2014 VL 15 SU 15 AR S2 DI 10.1186/1471-2105-15-S15-S2 PG 11 WC Biochemical Research Methods; Biotechnology & Applied Microbiology; Mathematical & Computational Biology SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Mathematical & Computational Biology GA AW3EG UT WOS:000346167900002 PM 25473795 ER PT J AU Lutas, A Birnbaumer, L Yellen, G AF Lutas, Andrew Birnbaumer, Lutz Yellen, Gary TI Metabolism Regulates the Spontaneous Firing of Substantia Nigra Pars Reticulata Neurons via K-ATP and Nonselective Cation Channels SO JOURNAL OF NEUROSCIENCE LA English DT Article DE excitability; glycolysis; KATP; Trp channel ID GLYCERALDEHYDE-3-PHOSPHATE DEHYDROGENASE; GLYCOLYTIC-ENZYMES; POTASSIUM CHANNELS; CHILDHOOD EPILEPSY; GABAERGIC NEURONS; KETOGENIC DIETS; TRPC3 CHANNELS; MICE; SEIZURE; BRAIN AB Neurons use glucose to fuel glycolysis and provide substrates for mitochondrial respiration, but neurons can also use alternative fuels that bypass glycolysis and feed directly into mitochondria. To determine whether neuronal pacemaking depends on active glucose metabolism, we switched the metabolic fuel from glucose to alternative fuels, lactate or beta-hydroxybutyrate, while monitoring the spontaneous firing of GABAergic neurons in mouse substantia nigra pars reticulata (SNr) brain slices. We found that alternative fuels, in the absence of glucose, sustained SNr spontaneous firing at basal rates, but glycolysis may still be supported by glycogen in the absence of glucose. To prevent any glycogen-fueled glycolysis, we directly inhibited glycolysis using either 2-deoxyglucose or iodoacetic acid. Inhibiting glycolysis in the presence of alternative fuels lowered SNr firing to a slower sustained firing rate. Surprisingly, we found that the decrease in SNr firing was not mediated by ATP-sensitive potassium (K-ATP) channel activity, but if we lowered the perfusion flow rate or omitted the alternative fuel, K-ATP channels were activated and could silence SNr firing. The K-ATP-independent slowing of SNr firing that occurred with glycolytic inhibition in the presence of alternative fuels was consistent with a decrease in a nonselective cationic conductance. Although mitochondrial metabolism alone can prevent severe energy deprivation and K-ATP channel activation in SNr neurons, active glucose metabolism appears important for keeping open a class of ion channels that is crucial for the high spontaneous firing rate of SNr neurons. C1 [Lutas, Andrew; Yellen, Gary] Harvard Univ, Sch Med, Dept Neurobiol, Boston, MA 02115 USA. [Birnbaumer, Lutz] Natl Inst Environm Res, Neurobiol Lab, NIH, Res Triangle Pk, NC 27709 USA. RP Yellen, G (reprint author), Harvard Univ, Sch Med, Dept Neurobiol, 220 Longwood Ave, Boston, MA 02115 USA. EM gary_yellen@hms.harvard.edu OI Lutas, Andrew/0000-0002-6991-2898; Yellen, Gary/0000-0003-4228-7866 FU National Institutes of Health (NIH)/National Institute of Neurological Disorders and Stroke [R01 NS055031, F31 NS077633]; NIH Intramural Research Program Project [Z01-ES-101684] FX This work was supported by National Institutes of Health (NIH)/National Institute of Neurological Disorders and Stroke Grants R01 NS055031 (G.Y.) and F31 NS077633 (A.L.) and NIH Intramural Research Program Project Z01-ES-101684 (L.B.). We thank members of the Yellen laboratory for valuable discussions and comments. We are also grateful to Drs. Bruce Bean, Michael Do, and Chinfei Chen for helpful advice. Kir6.2 knock-out mice were generously provided by Drs. Susumu Seino and Colin Nichols. NR 56 TC 10 Z9 10 U1 0 U2 11 PU SOC NEUROSCIENCE PI WASHINGTON PA 11 DUPONT CIRCLE, NW, STE 500, WASHINGTON, DC 20036 USA SN 0270-6474 J9 J NEUROSCI JI J. Neurosci. PD DEC 3 PY 2014 VL 34 IS 49 BP 16336 EP 16347 DI 10.1523/JNEUROSCI.1357-14.2014 PG 12 WC Neurosciences SC Neurosciences & Neurology GA AW2WJ UT WOS:000346147100015 PM 25471572 ER PT J AU Dayan, E Hamann, JM Averbeck, BB Cohen, LG AF Dayan, Eran Hamann, Janne M. Averbeck, Bruno B. Cohen, Leonardo G. TI Brain Structural Substrates of Reward Dependence during Behavioral Performance SO JOURNAL OF NEUROSCIENCE LA English DT Article DE brain structure; motivation; prefrontal cortex; reward ID TRANSCRANIAL MAGNETIC STIMULATION; SUPERIOR FRONTAL GYRUS; INDIVIDUAL-DIFFERENCES; SKILL ACQUISITION; PREFRONTAL CORTEX; DECISION-MAKING; FMRI; COGNITION; PUNISHMENT; STRIATUM AB Interindividual differences in the effects of reward on performance are prevalent and poorly understood, with some individuals being more dependent than others on the rewarding outcomes of their actions. The origin of this variability in reward dependence is unknown. Here, we tested the relationship between reward dependence and brain structure in healthy humans. Subjects trained on a visuomotor skill-acquisition task and received performance feedback in the presence or absence of reward. Reward dependence was defined as the statistical trial-by-trial relation between reward and subsequent performance. We report a significant relationship between reward dependence and the lateral prefrontal cortex, where regional gray-matter volume predicted reward dependence but not feedback alone. Multivoxel pattern analysis confirmed the anatomical specificity of this relationship. These results identified a likely anatomical marker for the prospective influence of reward on performance, which may be of relevance in neurorehabilitative settings. C1 [Dayan, Eran; Hamann, Janne M.; Cohen, Leonardo G.] NINDS, Human Cort Physiol & Neurorehabil Sect, Bethesda, MD 20892 USA. [Averbeck, Bruno B.] NIH, Neuropsychol Lab, Bethesda, MD 20892 USA. [Hamann, Janne M.] Univ Med Ctr Hamburg Eppendorf, D-20251 Hamburg, Germany. RP Dayan, E (reprint author), NIH, 10 Ctr Dr,Bldg 10, Bethesda, MD 20892 USA. EM dayane@ninds.nih.gov; cohenl@ninds.nih.gov FU Intramural Research Program of the National Institute of Neurological Disorders and Stroke; National Institutes of Health FX This work was supported by the Intramural Research Program of the National Institute of Neurological Disorders and Stroke, National Institutes of Health. This study used the high-performance computational capabilities of the Biowulf Linux cluster at the National Institutes of Health, Bethesda, MD (http://biowulf.nih.gov). We thank George Dold, Gary Melvin, and Ksenia Zherdeva for technical help and Nitzan Censor, Javier Elkin, and Micah Allen for helpful advice and suggestions. NR 62 TC 4 Z9 4 U1 3 U2 12 PU SOC NEUROSCIENCE PI WASHINGTON PA 11 DUPONT CIRCLE, NW, STE 500, WASHINGTON, DC 20036 USA SN 0270-6474 J9 J NEUROSCI JI J. Neurosci. PD DEC 3 PY 2014 VL 34 IS 49 BP 16433 EP 16441 DI 10.1523/JNEUROSCI.3141-14.2014 PG 9 WC Neurosciences SC Neurosciences & Neurology GA AW2WJ UT WOS:000346147100024 PM 25471581 ER PT J AU Chen, RY Dodd, LE Lee, M Paripati, P Hammoud, DA Mountz, JM Jeon, D Zia, N Zahiri, H Coleman, MT Carroll, MW Lee, JD Jeong, YJ Herscovitch, P Lahouar, S Tartakovsky, M Rosenthal, A Somaiyya, S Lee, S Goldfeder, LC Cai, Y Via, LE Park, SK Cho, SN Barry, CE AF Chen, Ray Y. Dodd, Lori E. Lee, Myungsun Paripati, Praveen Hammoud, Dima A. Mountz, James M. Jeon, Doosoo Zia, Nadeem Zahiri, Homeira Coleman, M. Teresa Carroll, Matthew W. Lee, Jong Doo Jeong, Yeon Joo Herscovitch, Peter Lahouar, Saher Tartakovsky, Michael Rosenthal, Alexander Somaiyya, Sandeep Lee, Soyoung Goldfeder, Lisa C. Cai, Ying Via, Laura E. Park, Seung-Kyu Cho, Sang-Nae Barry, Clifton E., III TI PET/CT imaging correlates with treatment outcome in patients with multidrug-resistant tuberculosis SO SCIENCE TRANSLATIONAL MEDICINE LA English DT Article ID POSITRON-EMISSION-TOMOGRAPHY; RESOLUTION COMPUTED-TOMOGRAPHY; ACTIVE PULMONARY TUBERCULOSIS; THERAPEUTIC RESPONSE; FDG-PET; INTRAOBSERVER VARIABILITY; DISEASE-ACTIVITY; F-18-FDG PET/CT; LUNG-CANCER; CHEST CT AB Definitive clinical trials of new chemotherapies for treating tuberculosis (TB) require following subjects until at least 6 months after treatment discontinuation to assess for durable cure, making these trials expensive and lengthy. Surrogate endpoints relating to treatment failure and relapse are currently limited to sputum microbiology, which has limited sensitivity and specificity. We prospectively assessed radiographic changes using 2-deoxy-2-[F-18]-fluoro-D-glucose (FDG) positron emission tomography/computed tomography (PET/CT) at 2 and 6 months (CT only) in a cohort of subjects with multidrug-resistant TB, who were treated with second-line TB therapy for 2 years and then followed for an additional 6 months. CT scans were read semiquantitatively by radiologists and were computationally evaluated using custom software to provide volumetric assessment of TB-associated abnormalities. CT scans at 6 months (but not 2 months) assessed by radiologist readers were predictive of outcomes, and changes in computed abnormal volumes were predictive of drug response at both time points. Quantitative changes in FDG uptake 2 months after starting treatment were associated with long-term outcomes. In this cohort, some radiologic markers were more sensitive than conventional sputum microbiology in distinguishing successful from unsuccessful treatment. These results support the potential of imaging scans as possible surrogate endpoints in clinical trials of new TB drug regimens. Larger cohorts confirming these results are needed. C1 [Chen, Ray Y.; Carroll, Matthew W.; Goldfeder, Lisa C.; Cai, Ying; Via, Laura E.; Cho, Sang-Nae] NIAID, TB Res Sect, Lab Clin Infect Dis, NIH, Bethesda, MD 20892 USA. [Dodd, Lori E.] NIAID, Biostat Res Branch, NIH, Bethesda, MD 20892 USA. [Lee, Myungsun; Lee, Soyoung; Cho, Sang-Nae] Int TB Res Ctr, Chang Won 631710, South Korea. [Paripati, Praveen; Lahouar, Saher; Somaiyya, Sandeep] NET Esolut Corp NETE, NETE FGI Imaging Team, Mclean, VA 22102 USA. [Hammoud, Dima A.; Zahiri, Homeira] NIH, Div Diagnost Radiol, Ctr Clin, Bethesda, MD 20892 USA. [Mountz, James M.; Zia, Nadeem; Coleman, M. Teresa] Univ Pittsburgh, Dept Radiol, Pittsburgh, PA 15260 USA. [Jeon, Doosoo; Park, Seung-Kyu] Natl Masan Hosp, Chang Won 631710, South Korea. [Lee, Jong Doo] Yonsei Univ, Dept Nucl Med, Coll Med, Seoul 120752, South Korea. [Jeong, Yeon Joo] Pusan Natl Univ, Dept Diagnost Radiol, Sch Med, Pusan 609735, South Korea. [Herscovitch, Peter] NIH, PET Dept, Ctr Clin, Bethesda, MD 20892 USA. [Tartakovsky, Michael; Rosenthal, Alexander] NIAID, Off Cyber Infrastruct & Computat Biol, NIH, Bethesda, MD 20892 USA. [Cho, Sang-Nae] Yonsei Univ, Dept Microbiol, Coll Med, Seoul 120752, South Korea. [Cho, Sang-Nae] Yonsei Univ, Inst Immunol & Immunol Dis, Coll Med, Seoul 120752, South Korea. [Barry, Clifton E., III] Univ Cape Town, Inst Infect Dis & Mol Med, Fac Hlth Sci, ZA-7701 Rondebosch, South Africa. [Barry, Clifton E., III] Univ Cape Town, Dept Clin Lab Sci, Fac Hlth Sci, ZA-7701 Rondebosch, South Africa. RP Barry, CE (reprint author), NIAID, TB Res Sect, Lab Clin Infect Dis, NIH, Bethesda, MD 20892 USA. EM cbarry@niaid.nih.gov RI Hammoud, Dima/C-2286-2015; Barry, III, Clifton/H-3839-2012; OI Chen, Ray/0000-0001-6344-1442 FU Intramural Research Program of the National Institute of Allergy and Infectious Diseases, NIH; Ministry of Health and Welfare, Republic of Korea FX Funding for this study was provided by the Intramural Research Program of the National Institute of Allergy and Infectious Diseases, NIH, and by the Ministry of Health and Welfare, Republic of Korea. NR 46 TC 28 Z9 28 U1 0 U2 8 PU AMER ASSOC ADVANCEMENT SCIENCE PI WASHINGTON PA 1200 NEW YORK AVE, NW, WASHINGTON, DC 20005 USA SN 1946-6234 EI 1946-6242 J9 SCI TRANSL MED JI Sci. Transl. Med. PD DEC 3 PY 2014 VL 6 IS 265 AR 265ra166 DI 10.1126/scitranslmed.3009501 PG 9 WC Cell Biology; Medicine, Research & Experimental SC Cell Biology; Research & Experimental Medicine GA AU9MD UT WOS:000345916300001 PM 25473034 ER PT J AU Coleman, MT Chen, RY Lee, M Lin, PL Dodd, LE Maiello, P Via, LE Kim, Y Marriner, G Dartois, V Scanga, C Janssen, C Wang, J Klein, E Cho, SN Barry, CE Flynn, JL AF Coleman, M. Teresa Chen, Ray Y. Lee, Myungsun Lin, Philana Ling Dodd, Lori E. Maiello, Pauline Via, Laura E. Kim, Youngran Marriner, Gwendolyn Dartois, Veronique Scanga, Charles Janssen, Christopher Wang, Jing Klein, Edwin Cho, Sang Nae Barry, Clifton E., III Flynn, JoAnne L. TI PET/CT imaging reveals a therapeutic response to oxazolidinones in macaques and humans with tuberculosis SO SCIENCE TRANSLATIONAL MEDICINE LA English DT Article ID MYCOBACTERIUM-TUBERCULOSIS; RESISTANT TUBERCULOSIS; INFECTION; SPECTRUM; DRUGS; TB AB Oxazolidinone antibiotics such as linezolid have shown significant therapeutic effects in patients with extensively drug-resistant (XDR) tuberculosis (TB) despite modest effects in rodents and no demonstrable early bactericidal activity in human phase 2 trials. We show that monotherapy with either linezolid or AZD5847, a second-generation oxazolidinone, reduced bacterial load at necropsy in Mycobacterium tuberculosis-infected cynomolgus macaques with active TB. This effect coincided with a decline in 2-deoxy-2-[F-18]-fluoro-D-glucose positron emission tomography (FDG PET) imaging avidity in the lungs of these animals and with reductions in pulmonary pathology measured by serial computed tomography (CT) scans over 2 months of monotherapy. In a parallel phase 2 clinical study of linezolid in patients infected with XDR-TB, we also collected PET/CT imaging data from subjects receiving linezolid that had been added to their failing treatment regimens. Quantitative comparisons of PET/CT imaging changes in these human subjects were similar inmagnitude to those observed in macaques, demonstrating that the therapeutic effect of these oxazolidinones can be reproduced in this model of experimental chemotherapy. PET/CT imaging may be useful as an early quantitative measure of drug efficacy against TB in human patients. C1 [Coleman, M. Teresa; Maiello, Pauline; Scanga, Charles; Flynn, JoAnne L.] Univ Pittsburgh, Dept Microbiol & Mol Genet, Sch Med, Pittsburgh, PA 15260 USA. [Chen, Ray Y.; Via, Laura E.; Marriner, Gwendolyn; Barry, Clifton E., III] NIAID, TB Res Sect, Lab Clin Infect Dis, NIH, Bethesda, MD 20892 USA. [Lee, Myungsun; Kim, Youngran; Cho, Sang Nae] Int TB Res Ctr, Chang Won 631710, South Korea. [Lin, Philana Ling] Univ Pittsburgh, Childrens Hosp Pittsburgh, Dept Pediat, Med Ctr, Pittsburgh, PA 15260 USA. [Dodd, Lori E.] NIAID, Biostat Res Branch, NIH, Bethesda, MD 20892 USA. [Dartois, Veronique] Rutgers New Jersey Med Sch, Publ Hlth Res Inst Ctr, Newark, NJ 07103 USA. [Janssen, Christopher; Klein, Edwin] Univ Pittsburgh, Div Lab Anim Resources, Pittsburgh, PA 15260 USA. [Wang, Jing] Leidos Biomed Res Inc, Frederick Natl Lab Canc Res, Clin Res Directorate, Clin Monitoring Res Program, Frederick, MD 21701 USA. [Cho, Sang Nae] Yonsei Univ, Dept Microbiol, Coll Med, Seoul 120752, South Korea. [Barry, Clifton E., III] Univ Cape Town, Inst Infect Dis & Mol Med, Fac Hlth Sci, ZA-7701 Rondebosch, South Africa. [Barry, Clifton E., III] Univ Cape Town, Dept Clin Lab Sci, Fac Hlth Sci, ZA-7701 Rondebosch, South Africa. RP Barry, CE (reprint author), NIAID, TB Res Sect, Lab Clin Infect Dis, NIH, Bethesda, MD 20892 USA. EM cbarry@niaid.nih.gov; joanne@pitt.edu RI Barry, III, Clifton/H-3839-2012; OI Chen, Ray/0000-0001-6344-1442 FU Intramural Research Program of the NIH, National Institute of Allergy and Infectious Diseases; Ministry of Health and Welfare, Republic of Korea; Bill and Melinda Gates Foundation TB Drug Accelerator; National Cancer Institute, NIH [HHSN261200800001E] FX Funding for this study was provided by the Intramural Research Program of the NIH, National Institute of Allergy and Infectious Diseases; by the Ministry of Health and Welfare, Republic of Korea; by the Bill and Melinda Gates Foundation TB Drug Accelerator; and by the National Cancer Institute, NIH, under contract no. HHSN261200800001E. The content of this publication does not necessarily reflect the views or policies of the Department of Health and Human Services, nor does mention of trade names, commercial products, or organizations imply endorsement by the U.S. government. NR 32 TC 31 Z9 31 U1 1 U2 6 PU AMER ASSOC ADVANCEMENT SCIENCE PI WASHINGTON PA 1200 NEW YORK AVE, NW, WASHINGTON, DC 20005 USA SN 1946-6234 EI 1946-6242 J9 SCI TRANSL MED JI Sci. Transl. Med. PD DEC 3 PY 2014 VL 6 IS 265 AR 265ra167 DI 10.1126/scitranslmed.3009500 PG 9 WC Cell Biology; Medicine, Research & Experimental SC Cell Biology; Research & Experimental Medicine GA AU9MD UT WOS:000345916300002 PM 25473035 ER PT J AU Hill, JM Quenelle, DC Cardin, RD Vogel, JL Clement, C Bravo, FJ Foster, TP Bosch-Marce, M Raja, P Lee, JS Bernstein, DI Krause, PR Knipe, DM Kristie, TM AF Hill, James M. Quenelle, Debra C. Cardin, Rhonda D. Vogel, Jodi L. Clement, Christian Bravo, Fernando J. Foster, Timothy P. Bosch-Marce, Marta Raja, Priya Lee, Jennifer S. Bernstein, David I. Krause, Philip R. Knipe, David M. Kristie, Thomas M. TI Inhibition of LSD1 reduces herpesvirus infection, shedding, and recurrence by promoting epigenetic suppression of viral genomes SO SCIENCE TRANSLATIONAL MEDICINE LA English DT Article ID SIMPLEX-VIRUS 1; HISTONE DEMETHYLASE LSD1; GENE-EXPRESSION; SELECTIVE-INHIBITION; TRIGEMINAL GANGLIA; HIV-1 ACQUISITION; CHROMATIN CONTROL; LATENT INFECTION; SUPER-ENHANCERS; CELLS AB Herpesviruses are highly prevalent and maintain lifelong latent reservoirs, thus posing challenges to the control of herpetic disease despite the availability of antiviral pharmaceuticals that target viral DNA replication. The initiation of herpes simplex virus infection and reactivation from latency is dependent on a transcriptional coactivator complex that contains two required histone demethylases, LSD1 (lysine-specific demethylase 1) and a member of the JMJD2 family (Jumonji C domain-containing protein 2). Inhibition of either of these enzymes results in heterochromatic suppression of the viral genome and blocks infection and reactivation in vitro. We demonstrate that viral infection can be epigenetically suppressed in three animal models of herpes simplex virus infection and disease. Treating animals with the monoamine oxidase inhibitor tranylcypromine to inhibit LSD1 suppressed viral lytic infection, subclinical shedding, and reactivation from latency in vivo. This phenotypic suppression was correlated with enhanced epigenetic suppression of the viral genome and suggests that, even during latency, the chromatin state of the virus is dynamic. Therefore, epi-pharmaceuticals may represent a promising approach to treat herpetic diseases. C1 [Hill, James M.; Clement, Christian; Foster, Timothy P.] Louisiana State Univ, Dept Ophthalmol, LSU Eye Ctr, Hlth Sci Ctr,Sch Med, New Orleans, LA 70112 USA. [Quenelle, Debra C.] Louisiana State Univ, Dept Microbiol Immunol & Parasitol, LSU Eye Ctr, Hlth Sci Ctr,Sch Med, New Orleans, LA 70112 USA. [Cardin, Rhonda D.; Bravo, Fernando J.; Bernstein, David I.] Univ Alabama Birmingham, Dept Pediat Infect Dis, Birmingham, AL 35294 USA. [Vogel, Jodi L.; Kristie, Thomas M.] Univ Cincinnati, Cincinnati Childrens Hosp Med Ctr, Div Infect Dis, Cincinnati, OH 45229 USA. [Bosch-Marce, Marta; Krause, Philip R.] US FDA, Ctr Biol Evaluat & Res, Bethesda, MD 20852 USA. [Raja, Priya; Lee, Jennifer S.; Knipe, David M.] Harvard Univ, Dept Microbiol & Immunol, Sch Med, Boston, MA 02115 USA. [Lee, Jennifer S.; Knipe, David M.] Harvard Univ, Harvard Program Virol, Sch Med, Boston, MA 02115 USA. RP Kristie, TM (reprint author), NIAID, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA. EM tkristie@niaid.nih.gov OI Krause, Philip/0000-0002-1045-7536; Lee, Jennifer/0000-0003-1324-6846 FU Laboratory of Viral Diseases, Division of Intramural Research, NIAID, NIH; National Eye Institute [R01-EY006311]; Research to Prevent Blindness (RPB); RPB; LSUHSC; U.S. Food and Drug Administration Intramural Funding; NIH [P01-AI098681]; [HHSN272201000027I]; [HHSN2720001]; [HHSN27220100008I] FX These studies were supported by the Laboratory of Viral Diseases, Division of Intramural Research, NIAID, NIH (T.M.K.); contract HHSN272201000027I, Task Order HHSN2720001 (D.C.Q.); National Eye Institute R01-EY006311 (J.M.H.), Research to Prevent Blindness (RPB) Senior Investigator Award (J.M.H.), RPB unrestricted grant to the LSU Eye Center (J.M.H.), LSUHSC unrestricted grant to J.M.H.; U.S. Food and Drug Administration Intramural Funding (P.R.K.); contract HHSN27220100008I (D.I.B. and R.D.C.); and NIH P01-AI098681 (D.M.K.). NR 63 TC 17 Z9 17 U1 3 U2 23 PU AMER ASSOC ADVANCEMENT SCIENCE PI WASHINGTON PA 1200 NEW YORK AVE, NW, WASHINGTON, DC 20005 USA SN 1946-6234 EI 1946-6242 J9 SCI TRANSL MED JI Sci. Transl. Med. PD DEC 3 PY 2014 VL 6 IS 265 AR 265ra169 DI 10.1126/scitranslmed.3010643 PG 9 WC Cell Biology; Medicine, Research & Experimental SC Cell Biology; Research & Experimental Medicine GA AU9MD UT WOS:000345916300004 PM 25473037 ER PT J AU Muhlestein, JB Lappe, DL Lima, JAC Rosen, BD May, HT Knight, S Bluemke, DA Towner, SR Le, V Bair, TL Vavere, AL Anderson, JL AF Muhlestein, Joseph B. Lappe, Donald L. Lima, Joao A. C. Rosen, Boaz D. May, Heidi T. Knight, Stacey Bluemke, David A. Towner, Steven R. Viet Le Bair, Tami L. Vavere, Andrea L. Anderson, Jeffrey L. TI Effect of Screening for Coronary Artery Disease Using CT Angiography on Mortality and Cardiac Events in High-Risk Patients With Diabetes The FACTOR-64 Randomized Clinical Trial SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Article ID AMERICAN-HEART-ASSOCIATION; COMPUTED-TOMOGRAPHY AB IMPORTANCE Coronary artery disease (CAD) is a major cause of cardiovascular morbidity and mortality in patients with diabetes mellitus, yet CAD often is asymptomatic prior to myocardial infarction (MI) and coronary death. OBJECTIVE To assess whether routine screening for CAD by coronary computed tomography angiography (CCTA) in patients with type 1 or type 2 diabetes deemed to be at high cardiac risk followed by CCTA-directed therapy would reduce the risk of death and nonfatal coronary outcomes. DESIGN, SETTING, AND PARTICIPANTS The FACTOR-64 study was a randomized clinical trial in which 900 patients with type 1 or type 2 diabetes of at least 3 to 5 years' duration and without symptoms of CAD were recruited from 45 clinics and practices of a single health system (Intermountain Healthcare, Utah), enrolled at a single-site coordinating center, and randomly assigned to CAD screening with CCTA (n = 452) or to standard national guidelines-based optimal diabetes care (n = 448) (targets: glycated hemoglobin level <7.0%, low-density lipoprotein cholesterol level <100 mg/dL, systolic blood pressure <130 mmHg). All CCTA imaging was performed at the coordinating center. Standard therapy or aggressive therapy (targets: glycated hemoglobin level <6.0%, low-density lipoprotein cholesterol level <70 mg/dL, high-density lipoprotein cholesterol level >50 mg/dL [women] or >40 mg/dL [men], triglycerides level <150 mg/dL, systolic blood pressure <120 mmHg), or aggressive therapy with invasive coronary angiography, was recommended based on CCTA findings. Enrollment occurred between July 2007 and May 2013, and follow-up extended to August 2014. MAIN OUTCOMES AND MEASURES The primary outcome was a composite of all-cause mortality, nonfatal MI, or unstable angina requiring hospitalization; the secondary outcome was ischemic major adverse cardiovascular events (composite of CAD death, nonfatal MI, or unstable angina). RESULTS At a mean follow-up time of 4.0 (SD, 1.7) years, the primary outcome event rates were not significantly different between the CCTA and the control groups (6.2%[28 events] vs 7.6%[34 events]; hazard ratio, 0.80 [95% CI, 0.49-1.32]; P = .38). The incidence of the composite secondary end point of ischemic major adverse cardiovascular events also did not differ between groups (4.4%[20 events] vs 3.8% [17 events]; hazard ratio, 1.15 [95% CI, 0.60-2.19]; P = .68). CONCLUSIONS AND RELEVANCE Among asymptomatic patients with type 1 or type 2 diabetes, use of CCTA to screen for CAD did not reduce the composite rate of all-cause mortality, nonfatal MI, or unstable angina requiring hospitalization at 4 years. These findings do not support CCTA screening in this population. C1 [Muhlestein, Joseph B.; Lappe, Donald L.; May, Heidi T.; Knight, Stacey; Towner, Steven R.; Viet Le; Bair, Tami L.; Anderson, Jeffrey L.] Intermt Med Ctr Heart Inst, Murray, UT 84107 USA. [Muhlestein, Joseph B.; Lappe, Donald L.; Knight, Stacey; Anderson, Jeffrey L.] Univ Utah, Sch Med, Salt Lake City, UT USA. [Lima, Joao A. C.; Rosen, Boaz D.; Vavere, Andrea L.] Johns Hopkins Univ, Dept Med, Div Cardiol, Baltimore, MD USA. [Bluemke, David A.] NIH, Dept Radiol & Imaging Sci, Ctr Clin, Bethesda, MD 20892 USA. RP Muhlestein, JB (reprint author), Intermt Med Ctr Heart Inst, 5121 S Cottonwood St, Murray, UT 84107 USA. EM brent.muhlestein@imail.org OI Le, Viet/0000-0001-6659-5332; May, Heidi/0000-0002-7524-5905; Bluemke, David/0000-0002-8323-8086; Knight, Stacey/0000-0003-0092-7327 FU Intermountain Research and Medical Foundation; Intermountain Healthcare Urban Central Region, Salt Lake City, Utah; Intermountain Heart Institute Department of Cardiovascular Research; Toshiba Corporation; Bracco Corporation FX This study was performed with the support of the Intermountain Research and Medical Foundation, Intermountain Healthcare Urban Central Region, Salt Lake City, Utah, and the Intermountain Heart Institute Department of Cardiovascular Research. In addition, the FACTOR-64 study was supported by grants from Toshiba Corporation and Bracco Corporation. NR 20 TC 80 Z9 81 U1 1 U2 10 PU AMER MEDICAL ASSOC PI CHICAGO PA 330 N WABASH AVE, STE 39300, CHICAGO, IL 60611-5885 USA SN 0098-7484 EI 1538-3598 J9 JAMA-J AM MED ASSOC JI JAMA-J. Am. Med. Assoc. PD DEC 3 PY 2014 VL 312 IS 21 BP 2234 EP 2243 DI 10.1001/jama.2014.15825 PG 10 WC Medicine, General & Internal SC General & Internal Medicine GA AU6AP UT WOS:000345684800018 PM 25402757 ER PT J AU Herrin, DM Coates, EE Costner, PJ Kemp, TJ Nason, MC Saharia, KK Pan, YJ Sarwar, UN Holman, L Yamshchikov, G Koup, RA Pang, YYS Seder, RA Schiller, JT Graham, BS Pinto, LA Ledgerwood, JE AF Herrin, Douglas M. Coates, Emily E. Costner, Pamela J. Kemp, Troy J. Nason, Martha C. Saharia, Kapil K. Pan, Yuanji Sarwar, Uzma N. Holman, Lasonji Yamshchikov, Galina Koup, Richard A. Pang, Yuk Ying S. Seder, Robert A. Schiller, John T. Graham, Barney S. Pinto, Ligia A. Ledgerwood, Julie E. TI Comparison of adaptive and innate immune responses induced by licensed vaccines for human papillomavirus SO HUMAN VACCINES & IMMUNOTHERAPEUTICS LA English DT Article DE adaptive immunity; adjuvant; human papillomavirus vaccine; immune signatures; innate immunity ID AGED 18-45 YEARS; CROSS-PROTECTIVE EFFICACY; MONOPHOSPHORYL-LIPID-A; VIRUS-LIKE PARTICLES; HPV-6/11/16/18 VACCINE; (HPV)-16/18 VACCINE; ANTIBODY-RESPONSES; CERVICAL-CANCER; CLINICAL-TRIAL; HPV TYPES AB Two HPV virus-like particle (VLP) vaccines, HPV-16/18 (GlaxoSmithKline, Cervarix (R)) and HPV-6/11/16/18 (Merck, Gardasil (R)), are currently licensed in the United States. Given the similar antigenic content but different adjuvant formulations in the 2 vaccines, they provide an efficient method for evaluating adjuvants and comparing the kinetics of the innate and adaptive immune responses. We randomized women to receive either Cervarix (R) or Gardasil (R), followed 6 month vaccination delivery schedules per manufacturer's recommendations, and analyzed the humoral immune response, T cell response, and circulating plasma cytokine levels in response to vaccination. Cervarix (R) recipients had higher anti-HPV-16 antibody and neutralization titers at month 7, and elevated anti-HPV-18 antibody and neutralization titers at months 7 and 12. Antibody avidity was similar for the 2 vaccines. HPV-31 was the only phylogenetically related non-vaccine HPV type, for which there is evidence of cross-protection, to be cross-neutralized and only in response to Cervarix (R). Comparing CD4(+) T cell cytokine responses at month 12, there was a trend of increased levels of IL-2 and TNF-alpha in the Cervarix (R) groups versus the Gardasil (R) groups that was consistent across all 4 tested HPV types (16/18/33/45). Elevated levels of circulating plasma cytokine/chemokines were observed post first vaccination in Gardasil (R) recipients and proinflammatory cytokines were elevated following 1(st) and 3(rd) Cervarix (R) vaccinations. Cervarix (R) and Gardasil (R) are both highly immunogenic vaccines. Higher antibody levels and CD4 T cell responses were achieved with Cervarix (R) after 3 doses, although similar affinity maturation was measured for the 2 vaccines. The clinical implications of the differences in immune responses are unknown. C1 [Herrin, Douglas M.; Coates, Emily E.; Costner, Pamela J.; Saharia, Kapil K.; Sarwar, Uzma N.; Holman, Lasonji; Yamshchikov, Galina; Koup, Richard A.; Seder, Robert A.; Graham, Barney S.; Ledgerwood, Julie E.] NIAID, Vaccine Res Ctr, NIH, Bethesda, MD 20892 USA. [Kemp, Troy J.; Pan, Yuanji; Pinto, Ligia A.] Leidos Biomed Res Inc, HPV Immunol Lab, Frederick Natl Lab Canc Res, Frederick, MD USA. [Nason, Martha C.] NIAID, Biostat Res Branch, Div Clin Res, NIH, Bethesda, MD 20892 USA. [Pang, Yuk Ying S.; Schiller, John T.] NCI, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. RP Ledgerwood, JE (reprint author), NIAID, Vaccine Res Ctr, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA. EM Ledgerwood@mail.nih.gov FU National Institutes of Health, National Institutes Intramural Research Program; National Cancer Institute, National Institutes of Health [HHSN261200800001E] FX This study was supported by the National Institutes of Health, National Institutes Intramural Research Program. ClinicalTrials.gov #NCT01132859 and in part with federal funds from the National Cancer Institute, National Institutes of Health, under Contract no. HHSN261200800001E. The content of this paper does not necessarily reflect the views or policies of the Department of Health and Human Services, nor does the mention of trade names, commercial products, or organizations imply endorsement by the US Government. NR 38 TC 3 Z9 3 U1 0 U2 7 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 530 WALNUT STREET, STE 850, PHILADELPHIA, PA 19106 USA SN 2164-5515 EI 2164-554X J9 HUM VACC IMMUNOTHER JI Human Vaccines Immunother. PD DEC 2 PY 2014 VL 10 IS 12 BP 3446 EP 3454 DI 10.4161/hv.34408 PG 9 WC Biotechnology & Applied Microbiology; Immunology SC Biotechnology & Applied Microbiology; Immunology GA CG6HA UT WOS:000353398100012 PM 25483691 ER PT J AU Casciotti, DM Smith, KC Klassen, AC AF Casciotti, Dana M. Smith, Katherine C. Klassen, Ann Carroll TI Topics associated with conflict in print news coverage of the HPV vaccine during 2005 to 2009 SO HUMAN VACCINES & IMMUNOTHERAPEUTICS LA English DT Article DE health communication; HPV vaccine; news media; conflict ID HUMAN-PAPILLOMAVIRUS VACCINE; MEDIA COVERAGE; CERVICAL-CANCER; NEWSPAPER COVERAGE; RISK MESSAGES; CONTROVERSY; GARDASIL; HEALTH; AGENDA; PREDICTORS AB HPV vaccines represent a significant advancement for cancer prevention, but vaccination against a sexually transmitted infection and possible vaccine mandates have created considerable negative publicity. We sought to understand media portrayal of vaccine-related controversy, and potential influences on attitudes and vaccine acceptance. We analyzed characteristics of media coverage of the HPV vaccine in 13 US newspapers between June 2005-May 2009, as well as relationships between conflict and pro-vaccine tone and specific story characteristics. The four-year timeframe was selected to capture coverage during the development of the vaccine, the period immediately pre- and post-approval, and the time of widespread recommendation and initial uptake. This allowed the exploration of a range of issues and provided an understanding of how coverage changed over time. Analysis included 447 news stories and opinion pieces, the majority of which were published in 2007. Most articles were positive (pro-vaccine) in tone, prompted by research/scientific advancement or legislative activities. We deemed 66% of all stories conflict-containing. Fewer articles from 2005-2006 and 2008-2009 contained conflict than those from 2007, suggesting a peak period of concern, followed by gradual acceptance of the HPV vaccine. Legislative activities and content related to sexual activity were sources of conflict in HPV vaccine media messages. Health communication strategies can be improved by understanding and addressing potential sources of conflict in news coverage of public health initiatives. C1 [Casciotti, Dana M.] NIH, Natl Lib Med, Bethesda, MD 20892 USA. [Smith, Katherine C.] Johns Hopkins Bloomberg Sch Publ Hlth, Dept Hlth Behav & Soc, Baltimore, MD USA. [Klassen, Ann Carroll] Drexel Univ, Sch Publ Hlth, Dept Community Hlth & Prevent, Philadelphia, PA 19104 USA. RP Klassen, AC (reprint author), Drexel Univ, Sch Publ Hlth, Dept Community Hlth & Prevent, Philadelphia, PA 19104 USA. EM ack57@drexel.edu FU Richard L Gelb Cancer Prevention Faculty Innovation Award; NCI Cancer Epidemiology, Prevention and Control Institutional Training Program at Johns Hopkins Bloomberg School of Public Health [T32 CA009314]; Johns Hopkins Carol Eliasberg Martin Scholarship in Cancer Prevention FX This research was supported in part by the Richard L Gelb Cancer Prevention Faculty Innovation Award to Dr. Klassen. Dr. Casciotti was also supported by the NCI Cancer Epidemiology, Prevention and Control Institutional Training Program at Johns Hopkins Bloomberg School of Public Health (T32 CA009314), and the Johns Hopkins Carol Eliasberg Martin Scholarship in Cancer Prevention. NR 45 TC 3 Z9 3 U1 2 U2 9 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 530 WALNUT STREET, STE 850, PHILADELPHIA, PA 19106 USA SN 2164-5515 EI 2164-554X J9 HUM VACC IMMUNOTHER JI Human Vaccines Immunother. PD DEC 2 PY 2014 VL 10 IS 12 BP 3466 EP 3474 DI 10.4161/21645515.2014.979622 PG 9 WC Biotechnology & Applied Microbiology; Immunology SC Biotechnology & Applied Microbiology; Immunology GA CG6HA UT WOS:000353398100014 PM 25668659 ER PT J AU Chatterjee, R He, XM Huang, D FitzGerald, P Smith, A Vinson, C AF Chatterjee, Raghunath He, Ximiao Huang, Di FitzGerald, Peter Smith, Andrew Vinson, Charles TI High-resolution genome-wide DNA methylation maps of mouse primary female dermal fibroblasts and keratinocytes SO EPIGENETICS & CHROMATIN LA English DT Article DE CG methylation; Hypomethylated regions; HMR; Methylome; CTCF; C/EBP beta; Keratinocytes; Fibroblasts ID RNA-POLYMERASE-II; BINDING-SITES; PROGENITOR CELLS; CPG METHYLATION; PROTEIN CTCF; CANCER; DIFFERENTIATION; TRANSCRIPTION; METHYLOME; SEQUENCES AB Background: Genome-wide DNA methylation at a single nucleotide resolution in different primary cells of the mammalian genome helps to determine the characteristics and functions of tissue-specific hypomethylated regions (TS-HMRs). We determined genome-wide cytosine methylation maps at 91X and 36X coverage of newborn female mouse primary dermal fibroblasts and keratinocytes and compared with mRNA-seq gene expression data. Results: These high coverage methylation maps were used to identify HMRs in both cell types. A total of 2.91% of the genome are in keratinocyte HMRs, and 2.15% of the genome are in fibroblast HMRs with 1.75% being common. Half of the TS-HMRs are extensions of common HMRs, and the remaining are unique TS-HMRs. Four levels of CG methylation are observed: 1) total unmethylation for CG dinucleotides in HMRs in CGIs that are active in all tissues; 2) 10% to 40% methylation for TS-HMRs; 3) 60% methylation for TS-HMRs in cells types where they are not in HMRs; and 4) 70% methylation for the nonfunctioning part of the genome. SINE elements are depleted inside the TS-HMRs, while highly enriched in the surrounding regions. Hypomethylation at the last exon shows gene repression, while demethylation toward the gene body positively correlates with gene expression. The overlapping HMRs have a more complex relationship with gene expression. The common HMRs and TS-HMRs are each enriched for distinct Transcription Factor Binding Sites (TFBS). C/EBP beta binds to methylated regions outside of HMRs while CTCF prefers to bind in HMRs, highlighting these two parts of the genome and their potential interactions. Conclusions: Keratinocytes and fibroblasts are of epithelial and mesenchymal origin. High-resolution methylation maps in these two cell types can be used as reference methylomes for analyzing epigenetic mechanisms in several diseases including cancer. C1 [Chatterjee, Raghunath; He, Ximiao; Vinson, Charles] NCI, Lab Metab, NIH, Bethesda, MD 20892 USA. [Chatterjee, Raghunath] Indian Stat Inst, Human Genet Unit, Kolkata 700108, India. [Huang, Di] NCBI, NIH, Bethesda, MD 20894 USA. [FitzGerald, Peter] NCI, Genome Anal Unit, Genet Branch, NIH, Bethesda, MD 20892 USA. [Smith, Andrew] Univ So Calif, Los Angeles, CA 90089 USA. RP Vinson, C (reprint author), NCI, Lab Metab, NIH, 37 Convent Dr, Bethesda, MD 20892 USA. EM vinsonc@mail.nih.gov FU intramural funding of National Cancer Institute, National Institutes of Health, MD, USA; Indian Statistical Institute, India FX This work is supported by the intramural funding of National Cancer Institute, National Institutes of Health, MD, USA. RC is supported by the intramural funding by Indian Statistical Institute, India. NR 61 TC 4 Z9 4 U1 0 U2 2 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1756-8935 J9 EPIGENET CHROMATIN JI Epigenetics Chromatin PD DEC 2 PY 2014 VL 7 AR 35 DI 10.1186/1756-8935-7-35 PG 13 WC Genetics & Heredity SC Genetics & Heredity GA AZ0JC UT WOS:000347930800001 PM 25699092 ER PT J AU Habbema, JDF Wilt, TJ Etzioni, R Nelson, HD Schechter, CB Lawrence, WF Melnikow, J Kuntz, KM Owens, DK Feuer, EJ AF Habbema, J. Dik F. Wilt, Timothy J. Etzioni, Ruth Nelson, Heidi D. Schechter, Clyde B. Lawrence, William F. Melnikow, Joy Kuntz, Karen M. Owens, Douglas K. Feuer, Eric J. TI Models in the Development of Clinical Practice Guidelines SO ANNALS OF INTERNAL MEDICINE LA English DT Article ID SERVICES TASK-FORCE; COLORECTAL-CANCER; RECOMMENDATION STATEMENT; BREAST-CANCER; UNITED-STATES; MORTALITY AB Clinical practice guidelines should be based on the best scientific evidence derived from systematic reviews of primary research. However, these studies often do not provide evidence needed by guideline development groups to evaluate the tradeoffs between benefits and harms. In this article, the authors identify 4 areas where models can bridge the gaps between published evidence and the information needed for guideline development applying new or updated information on disease risk, diagnostic test properties, and treatment efficacy; exploring a more complete array of alternative intervention strategies; assessing benefits and harms over a lifetime horizon; and projecting outcomes for the conditions for which the guideline is intended. The use of modeling as an approach to bridge these gaps (provided that the models are high-quality and adequately validated) is considered. Colorectal and breast cancer screening are used as examples to show the utility of models for these purposes. The authors propose that a modeling study is most useful when strong primary evidence is available to inform the model but critical gaps remain between the evidence and the questions that the guideline group must address. In these cases, model results have a place alongside the findings of systematic reviews to inform health care practice and policy. C1 Erasmus MC Univ Med Ctr, NL-3015 CN Rotterdam, Netherlands. Univ Minnesota, Sch Med, Minneapolis, MN 55455 USA. Fred Hutchinson Canc Res Ctr, Seattle, WA 98104 USA. Oregon Hlth & Sci Univ, Portland, OR 97201 USA. Albert Einstein Coll Med, New York, NY USA. Agcy Healthcare Res & Qual, Rockville, MD USA. UC Davis Med Ctr, Sacramento, CA USA. Stanford Univ, Stanford, CA 94305 USA. NCI, Bethesda, MD 20892 USA. RP Habbema, JDF (reprint author), Erasmus MC Univ Med Ctr, Dept Publ Hlth, Wytemaweg 80, NL-3015 CN Rotterdam, Netherlands. EM j.d.f.habbema@erasmusmc.nl FU U.S. Department of Veterans Affairs; Agency for Healthcare Research and Quality; American College of Physicians; National Kidney Foundation; Kidney Diseases International; National Institutes of Health; National Cancer Institute; California Health Benefits Review Program FX Dr. Wilt is supported by grants from the U.S. Department of Veterans Affairs and the Agency for Healthcare Research and Quality and contracts to conduct evidence synthesis from the American College of Physicians, the National Kidney Foundation, and Kidney Diseases International. Dr. Nelson is supported by the Agency for Healthcare Research and Quality and the National Institutes of Health. Dr. Schechter is supported by grants from the National Cancer Institute to develop and apply models of breast cancer epidemiology. Dr. Melnikow receives extramural support from the California Health Benefits Review Program and the National Institutes of Health. Dr. Owens is supported by the U.S. Department of Veterans Affairs. NR 37 TC 14 Z9 14 U1 1 U2 6 PU AMER COLL PHYSICIANS PI PHILADELPHIA PA INDEPENDENCE MALL WEST 6TH AND RACE ST, PHILADELPHIA, PA 19106-1572 USA SN 0003-4819 EI 1539-3704 J9 ANN INTERN MED JI Ann. Intern. Med. PD DEC 2 PY 2014 VL 161 IS 11 BP 812 EP U105 DI 10.7326/M14-0845 PG 8 WC Medicine, General & Internal SC General & Internal Medicine GA AX9UJ UT WOS:000347247200010 PM 25437409 ER PT J AU Decker, BK Sevransky, JE Barrett, K Davey, RT Chertow, DS AF Decker, Brooke K. Sevransky, Jonathan E. Barrett, Kevin Davey, Richard T. Chertow, Daniel S. TI Preparing for Critical Care Services to Patients With Ebola SO ANNALS OF INTERNAL MEDICINE LA English DT Editorial Material ID VIRUS TRANSMISSION C1 NIH, Bethesda, MD 20892 USA. Emory Univ Hosp, Med Intens Care Unit, Atlanta, GA 30322 USA. RP Decker, BK (reprint author), NIH, Ctr Clin, 10 Ctr Dr,Room 2C145, Bethesda, MD 20892 USA. EM brooke.decker@nih.gov OI Decker M.D., Brooke K/0000-0002-3404-9115 NR 7 TC 20 Z9 20 U1 0 U2 5 PU AMER COLL PHYSICIANS PI PHILADELPHIA PA INDEPENDENCE MALL WEST 6TH AND RACE ST, PHILADELPHIA, PA 19106-1572 USA SN 0003-4819 EI 1539-3704 J9 ANN INTERN MED JI Ann. Intern. Med. PD DEC 2 PY 2014 VL 161 IS 11 BP 831 EP U124 DI 10.7326/M14-2141 PG 3 WC Medicine, General & Internal SC General & Internal Medicine GA AX9UJ UT WOS:000347247200014 PM 25244048 ER PT J AU Baker, SG Lindeman, KS AF Baker, Stuart G. Lindeman, Karen S. TI Instrumental Variable Analyses for Observational Comparative Effectiveness Research: The Paired Availability Design SO ANNALS OF INTERNAL MEDICINE LA English DT Letter C1 [Baker, Stuart G.] NIH, Bethesda, MD 20892 USA. [Lindeman, Karen S.] Johns Hopkins Med, Baltimore, MD USA. RP Baker, SG (reprint author), NIH, Bldg 10, Bethesda, MD 20892 USA. NR 4 TC 1 Z9 1 U1 0 U2 1 PU AMER COLL PHYSICIANS PI PHILADELPHIA PA INDEPENDENCE MALL WEST 6TH AND RACE ST, PHILADELPHIA, PA 19106-1572 USA SN 0003-4819 EI 1539-3704 J9 ANN INTERN MED JI Ann. Intern. Med. PD DEC 2 PY 2014 VL 161 IS 11 BP 840 EP 841 DI 10.7326/L14-5029 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA AX9UJ UT WOS:000347247200020 PM 25437417 ER PT J AU Rubenstein, LV Danz, MS Crain, AL Glasgow, RE Whitebird, RR Solberg, LI AF Rubenstein, Lisa V. Danz, Marjorie S. Crain, A. Lauren Glasgow, Russell E. Whitebird, Robin R. Solberg, Leif I. TI Assessing organizational readiness for depression care quality improvement: relative commitment and implementation capability SO IMPLEMENTATION SCIENCE LA English DT Article DE Depression; Primary care; Quality improvement; Readiness; Measurement ID COLLABORATIVE CARE; RANDOMIZED-TRIAL; INTERVENTION; COSTS; MODEL AB Background: Depression is a major cause of morbidity and cost in primary care patient populations. Successful depression improvement models, however, are complex. Based on organizational readiness theory, a practice s commitment to change and its capability to carry out the change are both important predictors of initiating improvement. We empirically explored the links between relative commitment (i.e., the intention to move forward within the following year) and implementation capability. Methods: The DIAMOND initiative administered organizational surveys to medical and quality improvement leaders from each of 83 primary care practices in Minnesota. Surveys preceded initiation of activities directed at implementation of a collaborative care model for improving depression care. To assess implementation capability, we developed composites of survey items for five types of organizational factors postulated to be collaborative care barriers and facilitators. To assess relative commitment for each practice, we averaged leader ratings on an identical survey question assessing practice priorities. We used multivariable regression analyses to assess the extent to which implementation capability predicted relative commitment. We explored whether relative commitment or implementation capability measures were associated with earlier initiation of DIAMOND improvements. Results: All five implementation capability measures independently predicted practice leaders? relative commitment to improving depression care in the following year. These included the following: quality improvement culture and attitudes (p = 0.003), depression culture and attitudes (p < 0.001), prior depression quality improvement activities (p < 0.001), advanced access and tracking capabilities (p = 0.03), and depression collaborative care features in place (p = 0.03). Higher relative commitment (p = 0.002) and prior depression quality improvement activities appeared to be associated with earlier participation in the DIAMOND initiative. Conclusions: The study supports the concept of organizational readiness to improve quality of care and the use of practice leader surveys to assess it. Practice leaders relative commitment to depression care improvement may be a useful measure of the likelihood that a practice is ready to initiate evidence-based depression care changes. A comprehensive organizational assessment of implementation capability for depression care improvement may identify specific barriers or facilitators to readiness that require targeted attention from implementers. C1 [Rubenstein, Lisa V.; Danz, Marjorie S.] RAND Corp, Santa Monica, CA 90401 USA. [Rubenstein, Lisa V.; Danz, Marjorie S.] Vet Affairs Greater Los Angeles Healthcare Syst, North Hills, CA 91343 USA. [Crain, A. Lauren; Whitebird, Robin R.; Solberg, Leif I.] HealthPartners Res Fdn, Minneapolis, MN 55440 USA. [Glasgow, Russell E.] NCI, Div Canc Control & Populat Sci, Rockville, MD 20852 USA. RP Rubenstein, LV (reprint author), RAND Corp, 1776 Main St, Santa Monica, CA 90401 USA. EM lisar@rand.org FU National Institute of Mental Health [5R01MH080692] FX This research would not have been possible without the active support of many leaders and staff at the Institute for Clinical Systems Improvement, payers (Blue Cross and Blue Shield of Minnesota, First Plan, HealthPartners, Medica, Minnesota Department of Human Services, Preferred One, and U Care), and the medical groups and clinics. The success of the complex process for the clinical leader surveys is a tribute to both the leaders and study staff, in particular Kris Ohnsorg, Beth Molitor, and David Butani. The Veterans Affairs Center for Implementation Practice and Research Support (CIPRS) investigators and staff supported the manuscript development and preparation. The opinions expressed are those of the authors and do not necessarily represent those of the funding agency or the NIH. The support was provided by the National Institute of Mental Health grant number 5R01MH080692. NR 32 TC 2 Z9 2 U1 0 U2 10 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1748-5908 J9 IMPLEMENT SCI JI Implement. Sci. PD DEC 2 PY 2014 VL 9 AR 173 DI 10.1186/s13012-014-0173-1 PG 10 WC Health Care Sciences & Services; Health Policy & Services SC Health Care Sciences & Services GA AY2PT UT WOS:000347432600001 PM 25443652 ER PT J AU Sibley, CT Estwick, T Zavodni, A Huang, CY Kwan, AC Soule, BP Priel, DAL Remaley, AT Spergel, AKR Turkbey, EB Kuhns, DB Holland, SM Malech, HL Zarember, KA Bluemke, DA Gallin, JI AF Sibley, Christopher T. Estwick, Tyra Zavodni, Anna Huang, Chiung-Yu Kwan, Alan C. Soule, Benjamin P. Priel, Debra A. Long Remaley, Alan T. Spergel, Amanda K. Rudman Turkbey, Evrim B. Kuhns, Douglas B. Holland, Steven M. Malech, Harry L. Zarember, Kol A. Bluemke, David A. Gallin, John I. TI Assessment of Atherosclerosis in Chronic Granulomatous Disease SO CIRCULATION LA English DT Article DE atherosclerosis; carotid arteries; coronary vessels; immune system; inflammation ID CORONARY-ARTERY-DISEASE; INTIMA-MEDIA THICKNESS; NADPH OXIDASE; SUPEROXIDE-PRODUCTION; CARDIOVASCULAR EVENTS; OXIDATIVE STRESS; HIGH-RESOLUTION; CAROTID PLAQUE; APOE(-/-) MICE; EXPRESSION AB Background-Patients with chronic granulomatous disease (CGD) experience immunodeficiency because of defects in the phagocyte NADPH oxidase and the concomitant reduction in reactive oxygen intermediates. This may result in a reduction in atherosclerotic injury. Methods and Results-We prospectively assessed the prevalence of cardiovascular risk factors, biomarkers of inflammation and neutrophil activation, and the presence of magnetic resonance imaging and computed tomography quantified subclinical atherosclerosis in the carotid and coronary arteries of 41 patients with CGD and 25 healthy controls in the same age range. Univariable and multivariable associations among risk factors, inflammatory markers, and atherosclerosis burden were assessed. Patients with CGD had significant elevations in traditional risk factors and inflammatory markers compared with control subjects, including hypertension, high-sensitivity C-reactive protein, oxidized low-density lipoprotein, and low high-density lipoprotein. Despite this, patients with CGD had a 22% lower internal carotid artery wall volume compared with control subjects (361.3 +/- 76.4 mm(3) versus 463.5 +/- 104.7 mm(3); P<0.001). This difference was comparable in p47(phox)- and gp91(phox)-deficient subtypes of CGD and independent of risk factors in multivariate regression analysis. In contrast, the prevalence of coronary arterial calcification was similar between patients with CGD and control subjects (14.6%, CGD; 6.3%, controls; P=0.39). Conclusions-The observation by magnetic resonance imaging and computerized tomography of reduced carotid but not coronary artery atherosclerosis in patients with CGD despite the high prevalence of traditional risk factors raises questions about the role of NADPH oxidase in the pathogenesis of clinically significant atherosclerosis. Additional high-resolution studies in multiple vascular beds are required to address the therapeutic potential of NADPH oxidase inhibition in cardiovascular diseases. C1 [Sibley, Christopher T.; Zavodni, Anna; Kwan, Alan C.; Turkbey, Evrim B.; Bluemke, David A.] NIAID, Dept Radiol & Imaging Sci, NIH, Ctr Clin, Bethesda, MD 20892 USA. [Estwick, Tyra; Soule, Benjamin P.; Spergel, Amanda K. Rudman; Malech, Harry L.; Zarember, Kol A.; Gallin, John I.] NIAID, Lab Host Def, Bethesda, MD 20892 USA. [Huang, Chiung-Yu] NIAID, Biostat Res Branch, Bethesda, MD 20892 USA. [Holland, Steven M.] NIAID, Lab Clin Infect Dis, Bethesda, MD 20892 USA. [Remaley, Alan T.] NHLBI, NIH, Bethesda, MD 20892 USA. RP Gallin, JI (reprint author), NIAID, Lab Host Def, NIH, 10 Ctr Dr,Room 6-2551,MSC 1504, Bethesda, MD 20892 USA. EM jgallin@cc.nih.gov OI Malech, Harry/0000-0001-5874-5775; Bluemke, David/0000-0002-8323-8086 FU Division of Intramural Research of the National Institute of Allergy and Infectious Diseases; National Institutes of Health Clinical Center FX This work was supported by the Division of Intramural Research of the National Institute of Allergy and Infectious Diseases and the National Institutes of Health Clinical Center. NR 50 TC 11 Z9 11 U1 0 U2 4 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 EI 1524-4539 J9 CIRCULATION JI Circulation PD DEC 2 PY 2014 VL 130 IS 23 BP 2031 EP 2039 DI 10.1161/CIRCULATIONAHA.113.006824 PG 9 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA AW1EQ UT WOS:000346033700013 PM 25239440 ER PT J AU Lacro, RV Dietz, HC Sleeper, LA Yetman, AT Bradley, TJ Colan, SD Pearson, GD Tierney, ESS Levine, JC Atz, AM Benson, DW Braverman, AC Chen, S De Backer, J Gelb, BD Grossfeld, PD Klein, GL Lai, WW Liou, A Loeys, BL Markham, LW Olson, AK Paridon, SM Pemberton, VL Pierpont, ME Pyeritz, RE Radojewski, E Roman, MJ Sharkey, AM Stylianou, MP Wechsler, SB Young, LT Mahony, L AF Lacro, Ronald V. Dietz, Harry C. Sleeper, Lynn A. Yetman, Anji T. Bradley, Timothy J. Colan, Steven D. Pearson, Gail D. Tierney, Elif S. Selamet Levine, Jami C. Atz, Andrew M. Benson, D. W. Braverman, Alan C. Chen, Shan De Backer, Julie Gelb, Bruce D. Grossfeld, Paul D. Klein, Gloria L. Lai, Wyman W. Liou, Aimee Loeys, Bart L. Markham, Larry W. Olson, Aaron K. Paridon, Stephen M. Pemberton, Victoria L. Pierpont, Mary E. Pyeritz, Reed E. Radojewski, Elizabeth Roman, Mary J. Sharkey, Angela M. Stylianou, Mario P. Wechsler, Stephanie B. Young, Luciana T. Mahony, Lynn TI Randomized Trial of Atenolol Versus Losartan in Children and Young Adults With Marfan Syndrome SO CIRCULATION LA English DT Meeting Abstract CT Scientific Sessions of the American-Heart-Association and American-Stroke-Association / Resuscitation Science Symposium CY NOV 15-19, 2014 CL Chicago, IL SP Amer Heart Assoc, Amer Stroke Assoc DE Aortic aneurysm; Pediatric cardiology; Clinical trials; Beta-blocker; Drugs C1 [Lacro, Ronald V.; Colan, Steven D.; Tierney, Elif S. Selamet; Levine, Jami C.] Boston Childrens Hosp, Boston, MA USA. [Dietz, Harry C.] Johns Hopkins Univ, Sch Med, Baltimore, MD USA. [Sleeper, Lynn A.; Chen, Shan; Klein, Gloria L.] New England Rsch Inst, Pediat Heart Network, Watertown, MA USA. [Yetman, Anji T.] Primary Childrens Med Ctr, Salt Lake City, UT USA. [Yetman, Anji T.] Univ Utah, Salt Lake City, UT USA. [Bradley, Timothy J.] Hosp Sick Children, Toronto, ON M5G 1X8, Canada. [Pearson, Gail D.; Pemberton, Victoria L.; Radojewski, Elizabeth; Stylianou, Mario P.] NHLBI, NIH, Bethesda, MD 20892 USA. [Atz, Andrew M.] Med Univ S Carolina, Charleston, SC 29425 USA. [Benson, D. W.] Cincinnati Childrens Med Cntr, Cincinnati, OH USA. [Braverman, Alan C.; Sharkey, Angela M.] Washington Univ, Sch Med, St Louis, MO USA. [De Backer, Julie; Loeys, Bart L.] Univ Hosp Ghent, Ghent, Belgium. [Gelb, Bruce D.] Icahn Sch Med Mt Sinai, New York, NY 10029 USA. [Grossfeld, Paul D.] Univ Calif San Diego, Rady Childrens Hosp, San Diego, CA 92103 USA. [Lai, Wyman W.] Weill Med Coll, New York, NY USA. [Liou, Aimee] Texas Childrens Hosp, Houston, TX 77030 USA. [Markham, Larry W.] Vanderbilt Univ, Sch Med, Nashville, TN 37212 USA. [Olson, Aaron K.] Seattle Childrens Hosp, Seattle, WA USA. [Paridon, Stephen M.] Childrens Hosp Philadelphia, Philadelphia, PA 19104 USA. [Pierpont, Mary E.] Childrens Hosp, Minneapolis, MN USA. [Pierpont, Mary E.] Clin Minnesota, Minneapolis, MN USA. [Pyeritz, Reed E.] Univ Penn Hlth Syst, Philadelphia, PA USA. [Roman, Mary J.] New York Presbyterian Weill Cornell Med Coll, New York, NY USA. [Wechsler, Stephanie B.] Duke Univ, Med Cntr, Durham, NC USA. [Young, Luciana T.] Ann & Robert H Lurie Childrens Hosp Chicago, Chicago, IL USA. [Mahony, Lynn] UT Southwestern Med Cntr, Dallas, TX USA. NR 0 TC 0 Z9 0 U1 3 U2 8 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 EI 1524-4539 J9 CIRCULATION JI Circulation PD DEC 2 PY 2014 VL 130 IS 23 BP 2109 EP 2109 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA AW1EQ UT WOS:000346033700029 ER PT J AU Smith, PK Puskas, J Ascheim, D Voisine, P Ailawadi, G Hung, J Gelijns, A Moskowitz, AJ Perrault, L Parides, M Acker, M Argenziano, M Thourani, V Gammie, J Chen, F Miller, M Page, P Overbey, JR Bagiella, E Dagenais, F Blackstone, E Kron, I Goldstein, D Moquete, E Jeffries, N Gardner, T O'Gara, P Alexander, J Michler, RE AF Smith, Peter K. Puskas, John Ascheim, Deborah Voisine, Pierre Ailawadi, Gorav Hung, Judy Gelijns, Annetine Moskowitz, Alan J. Perrault, Louis Parides, Michael Acker, Michael Argenziano, Michael Thourani, Vinod Gammie, James Chen, Frederick Miller, Marissa Page, Pierre Overbey, Jessica R. Bagiella, Emilia Dagenais, Francois Blackstone, Eugene Kron, Irving Goldstein, Daniel Moquete, Ellen Jeffries, Neal Gardner, Timothy O'Gara, Patrick Alexander, John Michler, Robert E. TI The Surgical Treatment of Moderate Ischemic Mitral Regurgitation: A Randomized Clinical Trial From The Cardiothoracic Surgical Trials Network SO CIRCULATION LA English DT Meeting Abstract CT Scientific Sessions of the American-Heart-Association and American-Stroke-Association / Resuscitation Science Symposium CY NOV 15-19, 2014 CL Chicago, IL SP Amer Heart Assoc, Amer Stroke Assoc DE Mitral regurgitation; Coronary artery disease; Coronary artery bypass grafting (CABG); Valvuloplasty; Clinical trials C1 [Smith, Peter K.] Duke Univ, Durham, NC USA. [Puskas, John] Mt Sinai Beth Israel, Surg, New York, NY USA. [Ascheim, Deborah; Gelijns, Annetine; Moskowitz, Alan J.; Parides, Michael; Overbey, Jessica R.; Bagiella, Emilia] Icahn Sch Med Mt Sinai, New York, NY 10029 USA. [Voisine, Pierre] Inst Univ Cardiol Quebec, Quebec City, PQ, Canada. [Ailawadi, Gorav; Kron, Irving] Univ Virginia Hlth Syst, Charlottesville, VA USA. [Hung, Judy] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Perrault, Louis] Montreal Heart Inst, Montreal, PQ H1T 1C8, Canada. [Acker, Michael] Univ Penn, Philadelphia, PA 19104 USA. [Argenziano, Michael] Columbia Univ, Med Ctr, New York, NY USA. [Thourani, Vinod] Emory Univ Hosp Midtown, Atlanta, GA USA. [Gammie, James] Univ Maryland, Baltimore, MD 21201 USA. [Chen, Frederick] Brigham & Womens Hosp, Boston, MA 02115 USA. [Miller, Marissa; Jeffries, Neal] NHLBI, NIH, Bethesda, MD 20892 USA. [Page, Pierre] Hop Sacre Coeur, Montreal, PQ H4J 1C5, Canada. [Dagenais, Francois] Inst Univ Cardiol Quebec, Quebec City, PQ, Canada. [Blackstone, Eugene] Cleveland Clin, Cleveland, OH 44106 USA. [Goldstein, Daniel; Michler, Robert E.] Montefiore Einstein Heart Cntr, New York, NY USA. [Gardner, Timothy] Christiana Care Hlth Syst, Newark, DE USA. [O'Gara, Patrick] Brigham & Womens Hosp, Boston, MA 02115 USA. [Alexander, John] Duke Univ, Duke Clin Rsch Inst, Durham, NC USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 EI 1524-4539 J9 CIRCULATION JI Circulation PD DEC 2 PY 2014 VL 130 IS 23 BP 2110 EP 2110 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA AW1EQ UT WOS:000346033700032 ER PT J AU Pfeffer, M Rouleau, JL Claggett, B Diaz, R Clausell, N Gordeev, I Shaburishvili, T Lewis, EF Desai, A Anand, I Solomon, SD Fang, JC Sweitzer, NK Fleg, JL Boineau, R McKinlay, S Pitt, B AF Pfeffer, Marc Rouleau, Jean-Lucien Claggett, Brian Diaz, Rafael Clausell, Nadine Gordeev, Ivan Shaburishvili, Tamaz Lewis, Eldrin F. Desai, Akshay Anand, Inderjit Solomon, Scott D. Fang, James C. Sweitzer, Nancy K. Fleg, Jerome L. Boineau, Robin McKinlay, Sonja Pitt, Bertram TI Regional Analysis of Treatment of Preserved Cardiac Function Heart Failure With an Aldosterone Antagonist (TOPCAT) SO CIRCULATION LA English DT Meeting Abstract CT Scientific Sessions of the American-Heart-Association and American-Stroke-Association / Resuscitation Science Symposium CY NOV 15-19, 2014 CL Chicago, IL SP Amer Heart Assoc, Amer Stroke Assoc DE Heart failure; Cardiovascular therapeutics; Patient care C1 [Pfeffer, Marc; Claggett, Brian; Lewis, Eldrin F.; Desai, Akshay; Solomon, Scott D.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Boston, MA 02115 USA. [Rouleau, Jean-Lucien] Montreal Heart Res Inst, Montreal, PQ, Canada. [Diaz, Rafael] Estudios Cardiol Latinoamer, Rosario, Santa Fe, Argentina. [Clausell, Nadine] Hosp Clin Porto Alegre, Porto Alegre, RS, Brazil. [Gordeev, Ivan] State Healthcare Inst Moscow, Moscow, Russia. [Shaburishvili, Tamaz] Tbilisi Heart & Vasc Ctr, Tbilisi, Rep of Georgia. [Anand, Inderjit] VA Med Ctr, Minneapolis, MN USA. [Fang, James C.] Univ Utah, Salt Lake City, UT USA. [Sweitzer, Nancy K.] Univ Wisconsin, Madison, WI USA. [Fleg, Jerome L.; Boineau, Robin] NHLBI, Bethesda, MD 20892 USA. [McKinlay, Sonja] New England Res Inst, Watertown, MA 02172 USA. [Pitt, Bertram] Univ Michigan, Med Ctr, Ann Arbor, MI USA. RI Clausell, Nadine /C-7813-2016 OI Clausell, Nadine /0000-0003-4207-3809 NR 0 TC 0 Z9 0 U1 0 U2 4 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 EI 1524-4539 J9 CIRCULATION JI Circulation PD DEC 2 PY 2014 VL 130 IS 23 BP 2112 EP 2113 PG 2 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA AW1EQ UT WOS:000346033700039 ER PT J AU Wigginton, JG Abdelfattah, K Pepe, P Emerson, S Gatson, J Simpkins, J Bulger, E Foreman, M Hoyt, D Kerby, J Maass, D Madden, C May, S Minei, J Powell, J Ramsey, MA Roberts, J Saner, K Schug, K Egan, D Sopko, G Warren, V Idris, AH AF Wigginton, Jane G. Abdelfattah, Kareem Pepe, Paul Emerson, Scott Gatson, Joshua Simpkins, Jim Bulger, Eileen Foreman, Michael Hoyt, David Kerby, Jeff Maass, David Madden, Christopher May, Susanne Minei, Joseph Powell, Judy Ramsey, Michael A. Roberts, Jack Saner, Karla Schug, Kevin Egan, Debra Sopko, George Warren, Victoria Idris, Ahamed H. TI A Pilot Clinical Trial of Single-dose Estrogen for Resuscitation of Severe Traumatic Brain Injury (TBI) (RESCUE - TBI) SO CIRCULATION LA English DT Meeting Abstract CT Scientific Sessions of the American-Heart-Association and American-Stroke-Association / Resuscitation Science Symposium CY NOV 15-19, 2014 CL Chicago, IL SP Amer Heart Assoc, Amer Stroke Assoc DE Resuscitation; Clinical trials; Estrogen; Brain C1 [Wigginton, Jane G.; Abdelfattah, Kareem; Pepe, Paul; Gatson, Joshua; Maass, David; Minei, Joseph; Saner, Karla; Warren, Victoria; Idris, Ahamed H.] Univ Texas SW Med Ctr Dallas, Dallas, TX 75390 USA. [Emerson, Scott; Powell, Judy] W Virginia Univ, Morgantown, WV 26506 USA. [Simpkins, Jim] Baylor Hlth & Hosp Syst, Dallas, TX USA. [Foreman, Michael] Amer Coll Surg, Chicago, IL USA. [Hoyt, David] Univ Alabama Birmingham, Birmingham, AL USA. [Kerby, Jeff] Vanderbilt Univ, Nashville, TN 37235 USA. [Roberts, Jack] Univ Texas Arlington, Arlington, TX 76019 USA. [Schug, Kevin] NHLBI, Bethesda, MD 20892 USA. [Emerson, Scott; Bulger, Eileen; May, Susanne; Powell, Judy] Univ Washington, Seattle, WA 98195 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 0009-7322 EI 1524-4539 J9 CIRCULATION JI Circulation PD DEC 2 PY 2014 VL 130 IS 23 MA 13 BP 2122 EP 2122 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA AW1EQ UT WOS:000346033700061 ER PT J AU Wigginton, J Abdelfattah, K Gatson, J Pepe, P Emerson, S Simpkins, J Egan, D Foreman, M Hoyt, D Kerby, J Maass, D Madden, C May, S Minei, J Powell, J Ramsey, M Roberts, J Saner, K Schug, K Bulger, E Sopko, G Warren, VS Idris, A AF Wigginton, Jane Abdelfattah, Kareem Gatson, Joshua Pepe, Paul Emerson, Scott Simpkins, Jim Egan, Debra Foreman, Michael Hoyt, David Kerby, Jeff Maass, David Madden, Christopher May, Susanne Minei, Joseph Powell, Judy Ramsey, Michael Roberts, Jack Saner, Karla Schug, Kevin Bulger, Eileen Sopko, George Warren, Victoria S. Idris, Ahamed TI A Feasibility and Safety Pilot Clinical Trial of Single-dose, Intravenous Estrogen for Resuscitation of Traumatic Hemorrhagic Shock: The RESCUE - Shock Study SO CIRCULATION LA English DT Meeting Abstract CT Scientific Sessions of the American-Heart-Association and American-Stroke-Association / Resuscitation Science Symposium CY NOV 15-19, 2014 CL Chicago, IL SP Amer Heart Assoc, Amer Stroke Assoc DE Resuscitation; Clinical trials; Estrogen C1 [Wigginton, Jane; Abdelfattah, Kareem; Gatson, Joshua; Pepe, Paul; Maass, David; Madden, Christopher; Minei, Joseph; Saner, Karla; Warren, Victoria S.; Idris, Ahamed] Univ Texas SW Med Ctr Dallas, Dallas, TX 75390 USA. [Emerson, Scott; May, Susanne; Powell, Judy; Bulger, Eileen] Univ Washington, Seattle, WA 98195 USA. [Simpkins, Jim] W Virginia Univ, Morgantown, WV 26506 USA. [Egan, Debra; Sopko, George] NHLBI, Bethesda, MD 20892 USA. [Foreman, Michael; Ramsey, Michael] Baylor Hlth & Hosp Syst, Dallas, TX USA. [Hoyt, David] Amer Coll Surg, Chicago, IL USA. [Kerby, Jeff] Univ Alabama Birmingham, Birmingham, AL USA. [Roberts, Jack] Vanderbilt Univ, Nashville, TN 37235 USA. [Schug, Kevin] Univ Texas Arlington, Arlington, TX 76019 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 0009-7322 EI 1524-4539 J9 CIRCULATION JI Circulation PD DEC 2 PY 2014 VL 130 IS 23 MA 32 BP 2123 EP 2124 PG 2 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA AW1EQ UT WOS:000346033700066 ER PT J AU He, XM Chatterjee, R Tillo, D Smith, A FitzGerald, P Vinson, C AF He, Ximiao Chatterjee, Raghunath Tillo, Desiree Smith, Andrew FitzGerald, Peter Vinson, Charles TI Nucleosomes are enriched at the boundaries of hypomethylated regions (HMRs) in mouse dermal fibroblasts and keratinocytes SO EPIGENETICS & CHROMATIN LA English DT Article DE CG methylation; Hypomethylated regions; HMR; Nucleosomes; Epigenomics; Keratinocytes; Fibroblasts ID DNA METHYLATION; HUMAN GENOME; EPIGENETIC REGULATION; REGULATORY ELEMENTS; DEPLETED REGIONS; GENE-EXPRESSION; IN-VITRO; PROMOTERS; OCCUPANCY; SEQUENCES AB Background: The interplay between epigenetic modifications and chromatin structure are integral to our understanding of genome function. Methylation of cytosine (5mC) at CG dinucleotides, traditionally associated with transcriptional repression, is the most highly studied chemical modification of DNA, occurring at over 70% of all CG dinucleotides in the genome. Hypomethylated regions (HMRs) often occur in CG islands (CGIs), however, they also occur outside of CGIs and function as cell-type specific enhancers. During the process of differentiation, reorganization of chromatin and nucleosome arrangement at regulatory regions is thought to occur in order for the establishment of cell-type specific transcriptional programs. However, the specifics regarding the organization of nucleosomes at HMRs and the potential mechanisms regulating nucleosome occupancy in these regions are unknown. Here, we have investigated nucleosome organization around hypomethylated regions (HMRs) identified in two mouse primary cells. Results: Microccocal nuclease (MNase) digested mononucleosomes from primary cultures of new-born female mouse dermal fibroblasts and keratinocytes were mapped and compared to the HMRs obtained from single base pair resolution methylomes. In both cell types, we find that nucleosomes are enriched at HMR boundaries. In contrast to the nucleosomes found at boundaries of HMRs in CGIs, HMRs outside of CGIs are calculated to be preferentially bound by nucleosomes, with phased nucleosomes propagating into the methylated region. Nucleosomes are enriched at the tissue-specific HMRs (TS-HMR) boundaries in both cell types suggesting that nucleosome organization surrounding HMR boundaries is independent of methylation status. In addition, we find potential transcription factor (TF) binding sites (E-box motifs) enriched in non-CGI TS-HMR boundaries. Conclusions: Our results show that intrinsic nucleosome occupancy score (INOS) positively correlate with the nucleosome organization surrounding non-CGI TS-HMRs, suggesting that DNA sequence plays a role in the establishment of HMRs in the genome. Since nucleosomes impact all processes involving the genome, our results provide a link between epigenetic modifications, chromatin structure, and regulatory function. C1 [He, Ximiao; Chatterjee, Raghunath; Tillo, Desiree; Vinson, Charles] NCI, Lab Metab, NIH, Bethesda, MD 20892 USA. [Chatterjee, Raghunath] Indian Stat Inst, Human Genet Unit, Kolkata 700108, India. [Smith, Andrew] Univ So Calif, Los Angeles, CA 90089 USA. [FitzGerald, Peter] NCI, Genome Anal Unit, Genet Branch, NIH, Bethesda, MD 20892 USA. RP Vinson, C (reprint author), NCI, Lab Metab, NIH, 37 Convent Dr, Bethesda, MD 20892 USA. EM vinsonc@mail.nih.gov FU National Cancer Institute, National Institutes of Health, MD, USA; Indian Statistical Institute, India FX This work is supported by the intramural funding of National Cancer Institute, National Institutes of Health, MD, USA. RC is supported by the intramural funding by the Indian Statistical Institute, India. NR 56 TC 1 Z9 1 U1 0 U2 4 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1756-8935 J9 EPIGENET CHROMATIN JI Epigenetics Chromatin PD DEC 2 PY 2014 VL 7 AR 34 DI 10.1186/1756-8935-7-34 PG 10 WC Genetics & Heredity SC Genetics & Heredity GA AW3SM UT WOS:000346206500001 PM 25506399 ER PT J AU Logan, RA Kreps, GL AF Logan, Robert A. Kreps, Gary L. TI The NLM Evaluation Lecture Series: Introduction to the Special Section on Evaluating Health Communication Programs SO JOURNAL OF HEALTH COMMUNICATION LA English DT Article ID MEDICAID; CARE AB This article introduces the Journal of Health Communication's special section, Evaluating Health Communication Programs. This special section is based on a public lecture series supported by the National Library of Medicine titled "Better Health: Evaluating Health Communication Programs" designed to share best practices for using evaluation research to develop, implement, refine, and institutionalize the best health communication programs for promoting public health. This introduction provides an overview to the series, summarizes the major presentations in the series, and describe implications from the series for translational health communication research, interventions, and programs that can enhance health outcomes. C1 [Logan, Robert A.] Natl Lib Med, Off Commun & Publ Liaison, Bethesda, MD USA. [Kreps, Gary L.] George Mason Univ, Dept Commun, Fairfax, VA 22030 USA. RP Kreps, GL (reprint author), George Mason Univ, Dept Commun, MS 3D6, Fairfax, VA 22030 USA. EM gkreps@gmu.edu NR 14 TC 0 Z9 0 U1 0 U2 5 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 530 WALNUT STREET, STE 850, PHILADELPHIA, PA 19106 USA SN 1081-0730 EI 1087-0415 J9 J HEALTH COMMUN JI J. Health Commun. PD DEC 2 PY 2014 VL 19 IS 12 BP 1440 EP 1448 DI 10.1080/10810730.2014.954079 PG 9 WC Communication; Information Science & Library Science SC Communication; Information Science & Library Science GA AW1QJ UT WOS:000346064100009 PM 25491579 ER PT J AU Hesse, BW Gaysynsky, A Ottenbacher, A Moser, RP Blake, KD Chou, WYS Vieux, S Beckjord, E AF Hesse, Bradford W. Gaysynsky, Anna Ottenbacher, Allison Moser, Richard P. Blake, Kelly D. Chou, Wen-Ying Sylvia Vieux, Sana Beckjord, Ellen TI Meeting the Healthy People 2020 Goals: Using the Health Information National Trends Survey to Monitor Progress on Health Communication Objectives SO JOURNAL OF HEALTH COMMUNICATION LA English DT Article ID CARE PROVIDERS; INTERNET; HINTS AB The Healthy People initiative outlines a comprehensive set of goals aimed at improving the nation's health and reducing health disparities. Health communication has been included as an explicit goal since the launch of Healthy People 2010. The Health Information National Trends Survey (HINTS) was established as a means of exploring how the changing information environment was affecting the public's health, and is therefore an ideal tool for monitoring key health communication objectives included in the Healthy People agenda. In this article, the authors apply an integrative data analysis strategy to more than 10 years of HINTS data to demonstrate how public health surveillance can be used to evaluate broad national health goals, like those set forth under the Healthy People initiative. The authors analyzed just one item from the HINTS survey regarding Internet access in order to illustrate what public health surveillance tools, like HINTS, can reveal about important indicators that are of interest to all those who work to improve the health of the public. Results show that reported Internet penetration has exceeded the Healthy People 2020 target of 75.4%. HINTS data also allowed modeling of the effects of various sociodemographic factors, which revealed persistent differences on the basis of age and education, with the oldest age groups and those with less than a college education falling short of the Healthy People 2020 target as of 2013. Furthermore, although differences by race/ethnicity were observed, the analyses suggest that race in itself accounts for very little of the variance in Internet access. C1 [Hesse, Bradford W.; Gaysynsky, Anna; Ottenbacher, Allison; Moser, Richard P.; Blake, Kelly D.; Chou, Wen-Ying Sylvia] NCI, Bethesda, MD 20892 USA. [Vieux, Sana] Patient Ctr Outcomes Res Inst, Washington, DC USA. [Beckjord, Ellen] Univ Pittsburgh, Pittsburgh, PA USA. RP Hesse, BW (reprint author), NCI, 6130 Execut Blvd,MSC 7365,EPN 4068, Bethesda, MD 20892 USA. EM hesseb@mail.nih.gov OI Ottenbacher, Allison/0000-0002-8974-5580; Hesse, Bradford/0000-0003-1142-1161 FU Intramural NIH HHS [Z99 CA999999] NR 32 TC 4 Z9 4 U1 6 U2 11 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 530 WALNUT STREET, STE 850, PHILADELPHIA, PA 19106 USA SN 1081-0730 EI 1087-0415 J9 J HEALTH COMMUN JI J. Health Commun. PD DEC 2 PY 2014 VL 19 IS 12 BP 1497 EP 1509 DI 10.1080/10810730.2014.954084 PG 13 WC Communication; Information Science & Library Science SC Communication; Information Science & Library Science GA AW1QJ UT WOS:000346064100014 PM 25491584 ER PT J AU D'Souza, K Kim, YJ Balla, T Epand, RM AF D'Souza, Kenneth Kim, Yeun Ju Balla, Tamas Epand, Richard M. TI Distinct Properties of the Two Isoforms of CDP-Diacylglycerol Synthase SO BIOCHEMISTRY LA English DT Article ID ROD OUTER SEGMENTS; PHOSPHATIDIC-ACID; RAT-LIVER; PHOSPHATIDYLINOSITOL-CYCLE; PHOSPHOLIPASE-C; SPECIFICITY; PHOSPHOGLYCERIDES; PHOSPHOINOSITIDES; IDENTIFICATION; BIOSYNTHESIS AB CDP-diacylglycerol synthases (CDS) are critical enzymes that catalyze the formation of CDP-diacylglycerol (CDP-DAG) from phosphatidic acid (PA). Here we show in vitro that the two isoforms of human CDS, CDS1 and CDS2, show different acyl chain specificities for its lipid substrate. CDS2 is selective for the acyl chains at the sn-1 and sn-2 positions, the most preferred species being 1-stearoyl-2-arachidonoyl-sn-phosphatidic acid. CDS1, conversely, shows no particular substrate specificity, displaying similar activities for almost all substrates tested. Additionally, we show that inhibition of CDS2 by phosphatidylinositol is also acyl chain-dependent, with the strongest inhibition seen with the 1-stearoyl-2-arachidonoyl species. CDS1 shows no acyl chain-dependent inhibition. Both CDS1 and CDS2 are inhibited by their anionic phospholipid end products, with phosphatidylinositol-(4,5)-bisphosphate showing the strongest inhibition. Our results indicate that CDS1 and CDS2 could create different CDP-DAG pools that may serve to enrich different phospholipid species with specific acyl chains. C1 [D'Souza, Kenneth; Epand, Richard M.] McMaster Univ, Dept Biochem & Biomed Sci, Hamilton, ON L8N 3Z5, Canada. [Kim, Yeun Ju; Balla, Tamas] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Sect Mol Signal Transduct, Program Dev Neurosci, NIH, Bethesda, MD 20892 USA. RP Epand, RM (reprint author), McMaster Univ, Dept Biochem & Biomed Sci, 1280 Main St W, Hamilton, ON L8S 4K1, Canada. EM epand@mcmaster.ca OI Balla, Tamas/0000-0002-9077-3335 FU Natural Sciences and Engineering Council of Canada [9848]; Eunice Kennedy Shriver National Institute of Child Health and Human Development FX This work was partially supported by the Natural Sciences and Engineering Council of Canada (Grant 9848 to R.M.E.) and by the Intramural Research Program of the Eunice Kennedy Shriver National Institute of Child Health and Human Development (to T.B. and Y.J.K.). NR 38 TC 11 Z9 11 U1 2 U2 8 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0006-2960 J9 BIOCHEMISTRY-US JI Biochemistry PD DEC 2 PY 2014 VL 53 IS 47 BP 7358 EP 7367 DI 10.1021/bi501250m PG 10 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA AU7TM UT WOS:000345803600002 PM 25375833 ER PT J AU Dillard, P Varma, R Sengupta, K Limozin, L AF Dillard, Pierre Varma, Rajat Sengupta, Kheya Limozin, Laurent TI Ligand-Mediated Friction Determines Morphodynamics of Spreading T Cells SO BIOPHYSICAL JOURNAL LA English DT Article ID IMMUNOLOGICAL SYNAPSE; ACTIN CYTOSKELETON; RETROGRADE FLOW; ARTIFICIAL MEMBRANES; SIGNAL-TRANSDUCTION; TRACTION FORCES; ADHESION; ACTIVATION; RECEPTOR; DYNAMICS AB Spreading of T cells on antigen presenting cells is a crucial initial step in immune response. Spreading occurs through rapid morphological changes concomitant with the reorganization of surface receptors and of the cytoskeleton. Ligand mobility and frictional coupling of receptors to the cytoskeleton were separately recognized as important factors but a systematic study to explore their biophysical role in spreading was hitherto missing. To explore the impact of ligand mobility, we prepared chemically identical substrates on which molecules of anti-CD3 (capable of binding and activating the T cell receptor complex), were either immobilized or able to diffuse. We quantified the T cell spreading area and cell edge dynamics using quantitative reflection interference contrast microscopy, and imaged the actin distribution. On mobile ligands, as compared to fixed ligands, the cells spread much less, the actin is centrally, rather than peripherally distributed and the edge dynamics is largely altered. Blocking myosin-II or adding molecules of ICAM1 on the substrate largely abrogates these differences. We explain these observations by building a model based on the balance of forces between activation-dependent actin polymerization and actomyosin-generated tension on one hand, and on the frictional coupling of the ligand-receptor complexes with the actin cytoskeleton, the membrane and the substrate, on the other hand. Introducing the measured edge velocities in the model, we estimate the coefficient of frictional coupling between T Cell receptors or LFA-1 and the actin cytoskeleton. Our results provide for the first time, to our knowledge, a quantitative framework bridging T cell-specific biology with concepts developed for integrin-based mechanisms of spreading. C1 [Dillard, Pierre; Limozin, Laurent] Aix Marseille Univ, Inserm UMR 1067, CNRS UMR 7333, Marseille, France. [Dillard, Pierre; Sengupta, Kheya] Aix Marseille Univ, CINAM, CNRS UMR 7325, Marseille, France. [Varma, Rajat] NIAID, Lab Syst Biol, NIH, Bethesda, MD 20892 USA. RP Sengupta, K (reprint author), Aix Marseille Univ, CINAM, CNRS UMR 7325, Marseille, France. EM sengupta@cinam.univ-mrs.fr; laurent.limozin@inserm.fr RI Sengupta, Kheya/E-8629-2011; Limozin, Laurent/P-7134-2016 OI Sengupta, Kheya/0000-0002-1060-2713; FU European Research Council [307104 FP/2007-2013/ERC]; National Institute of Allergy and Infectious Diseases (NIAID), National Institutes of Health (NIH) FX K. S. thanks European Research Council for funding via grant No. 307104 FP/2007-2013/ERC. This work was in part supported by the intramural research program of National Institute of Allergy and Infectious Diseases (NIAID), National Institutes of Health (NIH). NR 56 TC 6 Z9 6 U1 1 U2 12 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 0006-3495 EI 1542-0086 J9 BIOPHYS J JI Biophys. J. PD DEC 2 PY 2014 VL 107 IS 11 BP 2629 EP 2638 DI 10.1016/j.bpj.2014.10.044 PG 10 WC Biophysics SC Biophysics GA AU8PU UT WOS:000345859500023 PM 25468342 ER PT J AU Goldstein, LB Lynch, J AF Goldstein, Larry B. Lynch, John TI Declining stroke mortality in young adults Hope and concern SO NEUROLOGY LA English DT Editorial Material ID ASSOCIATION; DEATH C1 [Goldstein, Larry B.] Duke Univ, Duke Stroke Ctr, Durham, NC 27706 USA. [Goldstein, Larry B.] Durham VA Med Ctr, Durham, NC USA. [Lynch, John] NINDS, Sect Stroke Diagnost & Therapeut, Bethesda, MD 20892 USA. RP Goldstein, LB (reprint author), Duke Univ, Duke Stroke Ctr, Durham, NC 27706 USA. EM golds004@mc.duke.edu NR 8 TC 0 Z9 0 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0028-3878 EI 1526-632X J9 NEUROLOGY JI Neurology PD DEC 2 PY 2014 VL 83 IS 23 BP 2102 EP 2103 PG 2 WC Clinical Neurology SC Neurosciences & Neurology GA AU8PJ UT WOS:000345858400002 PM 25361779 ER PT J AU Peng, Y Curtis, JE Fang, XY Woodson, SA AF Peng, Yi Curtis, Joseph E. Fang, Xianyang Woodson, Sarah A. TI Structural model of an mRNA in complex with the bacterial chaperone Hfq SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE small noncoding RNA; RNA-protein interactions; SAXS; Lsm protein; bacterial posttranscriptional control ID ESCHERICHIA-COLI HFQ; SM-LIKE PROTEIN; SOLUBLE-RNA; DUPLEX FORMATION; NONCODING RNAS; BINDING; RPOS; DSRA; RIBOREGULATION; RECOGNITION AB The Sm-like protein Hfq (host factor Q-beta phage) facilitates regulation by bacterial small noncoding RNAs (sRNAs) in response to stress and other environmental signals. Here, we present a low-resolution model of Escherichia coli Hfq bound to the rpoS mRNA, a bacterial stress response gene that is targeted by three different sRNAs. Selective 2'-hydroxyl acylation and primer extension, small-angle X-ray scattering, and Monte Carlo molecular dynamics simulations show that the distal face and lateral rim of Hfq interact with three sites in the rpoS leader, folding the RNA into a compact tertiary structure. These interactions are needed for sRNA regulation of rpoS translation and position the sRNA target adjacent to an sRNA binding region on the proximal face of Hfq. Our results show how Hfq specifically distorts the structure of the rpoS mRNA to enable sRNA base pairing and translational control. C1 [Peng, Yi] Johns Hopkins Univ, Cell Mol & Dev Biol & Biophys Program, Baltimore, MD 21218 USA. [Curtis, Joseph E.] NIST, Ctr Neutron Res, Gaithersburg, MD 20899 USA. [Fang, Xianyang] NCI, Struct Biophys Lab, Ctr Canc Res, NIH, Frederick, MD 21702 USA. [Woodson, Sarah A.] Johns Hopkins Univ, TC Jenkins Dept Biophys, Baltimore, MD 21218 USA. RP Woodson, SA (reprint author), Johns Hopkins Univ, TC Jenkins Dept Biophys, Baltimore, MD 21218 USA. EM swoodson@jhu.edu OI Woodson, Sarah/0000-0003-0170-1987 FU National Institute of General Medicine [R01 GM46686]; National Cancer Institute Center for Cancer Research; Engineering and Physical Sciences Research Council [EP/K039121/1]; National Science Foundation [CHE-1265821]; US Department of Energy under Contract [DE-AC02-06CH11357] FX The authors thank X. Zuo and the APS 12-ID-B staff, S. Krueger, S. Gottesman, G. Storz, and Y.-X. Wang for helpful discussion and D. Kilburn, S. Panja, N. Majdalani, N. Kim, and T. Schlick for their assistance. This work was supported by the National Institute of General Medicine (Grant R01 GM46686 to S. A. W.) and the National Cancer Institute Center for Cancer Research (Y.-X. Wang). This work benefited from CCP-SAS software developed through a joint Engineering and Physical Sciences Research Council (EP/K039121/1) and National Science Foundation (CHE-1265821) grant. Use of the Advanced Photon Source was supported by the US Department of Energy under Contract DE-AC02-06CH11357. NR 37 TC 21 Z9 23 U1 1 U2 25 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD DEC 2 PY 2014 VL 111 IS 48 BP 17134 EP 17139 DI 10.1073/pnas.1410114111 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA AU9NN UT WOS:000345920800044 PM 25404287 ER PT J AU Murin, CD Fusco, ML Bornholdt, ZA Qiu, XG Olinger, GG Zeitlin, L Kobinger, GP Ward, AB Saphire, EO AF Murin, Charles D. Fusco, Marnie L. Bornholdt, Zachary A. Qiu, Xiangguo Olinger, Gene G. Zeitlin, Larry Kobinger, Gary P. Ward, Andrew B. Saphire, Erica Ollmann TI Structures of protective antibodies reveal sites of vulnerability on Ebola virus SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE Ebola; ZMapp; EM; antibodies ID MUCIN-LIKE DOMAIN; MONOCLONAL-ANTIBODIES; NONHUMAN-PRIMATES; POSTEXPOSURE PROTECTION; NEUTRALIZING ANTIBODIES; MEDIATED PROTECTION; HEMORRHAGIC-FEVER; GLYCOPROTEIN SGP; RNA INTERFERENCE; GUINEA-PIGS AB Ebola virus (EBOV) and related filoviruses cause severe hemorrhagic fever, with up to 90% lethality, and no treatments are approved for human use. Multiple recent outbreaks of EBOV and the likelihood of future human exposure highlight the need for pre- and postexposure treatments. Monoclonal antibody (mAb) cocktails are particularly attractive candidates due to their proven postexposure efficacy in nonhuman primate models of EBOV infection. Two candidate cocktails, MB-003 and ZMAb, have been extensively evaluated in both in vitro and in vivo studies. Recently, these two therapeutics have been combined into a new cocktail named ZMapp, which showed increased efficacy and has been given compassionately to some human patients. Epitope information and mechanism of action are currently unknown for most of the component mAbs. Here we provide single-particle EM reconstructions of every mAb in the ZMapp cocktail, as well as additional antibodies from MB-003 and ZMAb. Our results illuminate key and recurring sites of vulnerability on the EBOV glycoprotein and provide a structural rationale for the efficacy of ZMapp. Interestingly, two of its components recognize overlapping epitopes and compete with each other for binding. Going forward, this work now provides a basis for strategic selection of next-generation antibody cocktails against Ebola and related viruses and a model for predicting the impact of ZMapp on potential escape mutations in ongoing or future Ebola outbreaks. C1 [Murin, Charles D.; Ward, Andrew B.] Scripps Res Inst, Dept Integrat Struct & Computat Biol, La Jolla, CA 92037 USA. [Murin, Charles D.; Fusco, Marnie L.; Bornholdt, Zachary A.; Saphire, Erica Ollmann] Scripps Res Inst, Dept Immunol & Microbial Sci, La Jolla, CA 92037 USA. [Saphire, Erica Ollmann] Scripps Res Inst, Skaggs Inst Chem Biol, La Jolla, CA 92037 USA. [Qiu, Xiangguo; Kobinger, Gary P.] Publ Hlth Agcy Canada, Natl Microbiol Lab, Winnipeg, MB R3E 3R2, Canada. [Olinger, Gene G.] NIAID, Integrated Res Facil, NIH, Frederick, MD 21702 USA. [Zeitlin, Larry] Mapp Biopharmaceut, San Diego, CA 92121 USA. [Kobinger, Gary P.] Univ Manitoba, Dept Med Microbiol, Winnipeg, MB R3E 0J9, Canada. [Kobinger, Gary P.] Univ Manitoba, Dept Immunol, Winnipeg, MB R3E 0T5, Canada. RP Ward, AB (reprint author), Scripps Res Inst, Dept Integrat Struct & Computat Biol, La Jolla, CA 92037 USA. EM abward@scripps.edu; erica@scripps.edu RI Ward, Andrew/F-9203-2014 OI Ward, Andrew/0000-0001-7153-3769 FU Biomedical Technology Research Center program of the National Institute of General Medical Sciences [GM103310]; National Science Foundation; Ray Thomas Edwards Foundation; Burroughs Welcome Fund; National Institutes of Health (NIH) [R01AI067927]; NIH/National Institute of Allergy and Infectious Diseases Center for Excellence in Translational Research Grant "Consortium for Immuno-therapeutics Against Viral Hemorrhagic Fevers" [U19AI109762] FX We thank Dr. Sheik Humarr Khan of Kenema Government Hospital and Dr. Pardis Sabeti of the Broad Institute for sharing unpublished sequence data for the 2014 West African Ebola virus isolates. We thank Dr. Gabriel Lander of The Scripps Research Institute (TSRI) for providing EMAN2 scripts and helpful advice. We also thank Kelsi Swope and Josh Morton from Kentucky Bioprocessing for preparing and sending IgGs. Finally, we thank Dr. Peter Lee and Dr. Gabriel Ozorowski, TSRI, for help with Octet experiments. Electron microscopy was conducted at the National Resource for Automated Molecular Microscopy at TSRI, which is supported by the Biomedical Technology Research Center program (GM103310) of the National Institute of General Medical Sciences. C.D.M. was supported by a predoctoral fellowship from the National Science Foundation, A.B.W. by a Ray Thomas Edwards Foundation award, and E.O.S. by Investigators in the Pathogenesis of Infectious Disease award from the Burroughs Welcome Fund. This work was supported by National Institutes of Health (NIH) Grant R01AI067927 (to E.O.S.) and NIH/National Institute of Allergy and Infectious Diseases Center for Excellence in Translational Research Grant U19AI109762 "Consortium for Immuno-therapeutics Against Viral Hemorrhagic Fevers" (to E.O.S., A.B.W., L.Z., and G.P.K.). This is manuscript 28016 from The Scripps Research Institute. NR 65 TC 52 Z9 56 U1 5 U2 84 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD DEC 2 PY 2014 VL 111 IS 48 BP 17182 EP 17187 DI 10.1073/pnas.1414164111 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA AU9NN UT WOS:000345920800052 PM 25404321 ER PT J AU Montague, MJ Li, G Gandolfi, B Khan, R Aken, BL Searle, SMJ Minx, P Hillier, LW Koboldt, DC Davis, BW Driscoll, CA Barr, CS Blackistone, K Quilez, J Lorente-Galdos, B Marques-Bonet, T Alkan, C Thomas, GWC Hahn, MW Menotti-Raymond, M O'Brien, SJ Wilson, RK Lyons, LA Murphy, WJ Warren, WC AF Montague, Michael J. Li, Gang Gandolfi, Barbara Khan, Razib Aken, Bronwen L. Searle, Steven M. J. Minx, Patrick Hillier, LaDeana W. Koboldt, Daniel C. Davis, Brian W. Driscoll, Carlos A. Barr, Christina S. Blackistone, Kevin Quilez, Javier Lorente-Galdos, Belen Marques-Bonet, Tomas Alkan, Can Thomas, Gregg W. C. Hahn, Matthew W. Menotti-Raymond, Marilyn O'Brien, Stephen J. Wilson, Richard K. Lyons, Leslie A. Murphy, William J. Warren, Wesley C. TI Comparative analysis of the domestic cat genome reveals genetic signatures underlying feline biology and domestication SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE Felis catus; domestication; genome ID MYOSIN-X; ACCELERATED EVOLUTION; SEQUENCE; MICE; POPULATIONS; DISCOVERY; SELECTION; HEARING; PROTEIN; BREEDS AB Little is known about the genetic changes that distinguish domestic cat populations from their wild progenitors. Here we describe a high-quality domestic cat reference genome assembly and comparative inferences made with other cat breeds, wildcats, and other mammals. Based upon these comparisons, we identified positively selected genes enriched for genes involved in lipid metabolism that underpin adaptations to a hypercarnivorous diet. We also found positive selection signals within genes underlying sensory processes, especially those affecting vision and hearing in the carnivore lineage. We observed an evolutionary tradeoff between functional olfactory and vomeronasal receptor gene repertoires in the cat and dog genomes, with an expansion of the feline chemosensory system for detecting pheromones at the expense of odorant detection. Genomic regions harboring signatures of natural selection that distinguish domestic cats from their wild congeners are enriched in neural crest-related genes associated with behavior and reward in mouse models, as predicted by the domestication syndrome hypothesis. Our description of a previously unidentified allele for the gloving pigmentation pattern found in the Birman breed supports the hypothesis that cat breeds experienced strong selection on specific mutations drawn from random bred populations. Collectively, these findings provide insight into how the process of domestication altered the ancestral wildcat genome and build a resource for future disease mapping and phylogenomic studies across all members of the Felidae. C1 [Montague, Michael J.; Minx, Patrick; Hillier, LaDeana W.; Koboldt, Daniel C.; Wilson, Richard K.; Warren, Wesley C.] Washington Univ, Sch Med, Genome Inst, St Louis, MO 63108 USA. [Li, Gang; Davis, Brian W.; Murphy, William J.] Texas A&M Univ, Coll Vet Med, Dept Vet Integrat Biosci, College Stn, TX 77843 USA. [Gandolfi, Barbara; Lyons, Leslie A.] Univ Missouri, Coll Vet Med, Dept Vet Med & Surg, Columbia, MO 65201 USA. [Khan, Razib] Univ Calif Davis, Sch Vet Med, Davis, CA 95616 USA. [Aken, Bronwen L.; Searle, Steven M. J.] Wellcome Trust Sanger Inst, Hinxton CB10 1SA, Cambs, England. [Driscoll, Carlos A.; Barr, Christina S.; Blackistone, Kevin] NIAAA, NIH, Bethesda, MD 20886 USA. [Quilez, Javier; Lorente-Galdos, Belen; Marques-Bonet, Tomas] Pompeu Fabra Univ, Inst Evolutionary Biol, Catalan Inst Res & Adv Studies, Barcelona 08003, Spain. [Marques-Bonet, Tomas] Ctr Anal Genom, Barcelona 08028, Spain. [Alkan, Can] Bilkent Univ, Dept Comp Engn, TR-06800 Ankara, Turkey. [Thomas, Gregg W. C.; Hahn, Matthew W.] Indiana Univ, Dept Biol, Bloomington, IN 47405 USA. [Menotti-Raymond, Marilyn] Ctr Canc Res, Lab Genom Divers, Frederick, MD 21702 USA. [O'Brien, Stephen J.] St Petersburg State Univ, Dobzhansky Ctr Genome Bioinformat, St Petersburg 199178, Russia. [O'Brien, Stephen J.] Nova SE Univ, Oceanog Ctr, Ft Lauderdale, FL 33314 USA. RP Lyons, LA (reprint author), Univ Missouri, Coll Vet Med, Dept Vet Med & Surg, Columbia, MO 65201 USA. EM lyonsla@missouri.edu; wmurphy@cvm.tamu.edu; wwarren@genome.wustl.edu RI Alkan, Can/D-2982-2009; li, gang/E-5640-2014; Quilez, Javier/J-7107-2015; OI Alkan, Can/0000-0002-5443-0706; Quilez, Javier/0000-0002-0108-2672; Lorente-Galdos, Belen/0000-0001-5390-2452; Montague, Michael/0000-0003-0253-4404; Aken, Bronwen/0000-0002-3032-4095; Marques-Bonet, Tomas/0000-0002-5597-3075; Driscoll, Carlos/0000-0003-2392-505X FU NIH/National Human Genome Research Institute [U54HG003079]; National Science Foundation [DBI-0845494]; Morris Animal Foundation [D06FE-063, D12FE-019]; European Research Council Starting [260372]; Spanish Government [BFU2011-28549]; National Center for Research Resources [R24 RR016094]; Office of Research Infrastructure Programs/Office of the Director [R24 OD010928]; Winn Feline Foundation [W10-014, W09-009] FX We thank The Genome Institute members Kim Kyung, Dave Larson, Karyn Meltz Steinburg, and Chad Tomlinson for providing assistance and advice on data analysis, and Tom Nicholas for manuscript review. We also thank NIH/National Institute on Alcohol Abuse and Alcoholism members David Goldman and Qiaoping Yuan. The cat genome and transcriptome sequencing was funded by NIH/National Human Genome Research Institute Grant U54HG003079 (to R. K. W.). Further research support included grants to M. W. H. (National Science Foundation Grant DBI-0845494), W. J. M. (Morris Animal Foundation Grants D06FE-063 and D12FE-019), T. M.-B. (European Research Council Starting Grant 260372 and Spanish Government Grant BFU2011-28549), and L. A. L. [National Center for Research Resources (R24 RR016094), Office of Research Infrastructure Programs/Office of the Director (R24 OD010928), and Winn Feline Foundation (W10-014, W09-009)]. NR 83 TC 47 Z9 47 U1 39 U2 222 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD DEC 2 PY 2014 VL 111 IS 48 BP 17230 EP 17235 DI 10.1073/pnas.1410083111 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA AU9NN UT WOS:000345920800060 PM 25385592 ER PT J AU Chavez, L Huang, Y Luong, K Agarwal, S Iyer, LM Pastor, WA Hench, VK Frazier-Bowers, SA Korol, E Liu, S Tahiliani, M Wang, YS Clark, TA Korlach, J Pukkila, PJ Aravind, L Rao, A AF Chavez, Lukas Huang, Yun Luong, Khai Agarwal, Suneet Iyer, Lakshminarayan M. Pastor, William A. Hench, Virginia K. Frazier-Bowers, Sylvia A. Korol, Evgenia Liu, Shuo Tahiliani, Mamta Wang, Yinsheng Clark, Tyson A. Korlach, Jonas Pukkila, Patricia J. Aravind, L. Rao, Anjana TI Simultaneous sequencing of oxidized methylcytosines produced by TET/JBP dioxygenases in Coprinopsis cinerea SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE TET; 5mC; 5fC; 5caC; SMRT-seq ID EMBRYONIC STEM-CELLS; BASIDIOMYCETE COPRINUS-CINEREUS; EUKARYOTIC DNA METHYLATION; SINGLE-MOLECULE; COMPLEX MODIFICATIONS; ESCHERICHIA-COLI; MAMMALIAN DNA; TET PROTEINS; 5-METHYLCYTOSINE; 5-HYDROXYMETHYLCYTOSINE AB TET/JBP enzymes oxidize 5-methylpyrimidines in DNA. In mammals, the oxidized methylcytosines (oxi-mCs) function as epigenetic marks and likely intermediates in DNA demethylation. Here we present a method based on diglucosylation of 5-hydroxymethylcytosine (5hmC) to simultaneously map 5hmC, 5-formylcytosine, and 5-carboxylcytosine at near-base-pair resolution. We have used the method to map the distribution of oxi-mC across the genome of Coprinopsis cinerea, a basidiomycete that encodes 47 TET/JBP paralogs in a previously unidentified class of DNA transposons. Like 5-methylcytosine residues from which they are derived, oxi-mC modifications are enriched at centromeres, TET/JBP transposons, and multicopy paralogous genes that are not expressed, but rarely mark genes whose expression changes between two developmental stages. Our study provides evidence for the emergence of an epigenetic regulatory system through recruitment of selfish elements in a eukaryotic lineage, and describes a method to map all three different species of oxi-mCs simultaneously. C1 [Chavez, Lukas; Huang, Yun; Pastor, William A.; Rao, Anjana] La Jolla Inst Allergy & Immunol, Div Signaling & Gene Express, La Jolla, CA 92037 USA. [Chavez, Lukas; Huang, Yun] Sanford Consortium Regenerat Med, La Jolla, CA 92037 USA. [Luong, Khai; Clark, Tyson A.; Korlach, Jonas] Pacific Biosci, Menlo Pk, CA 94025 USA. [Agarwal, Suneet] Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA. [Iyer, Lakshminarayan M.; Aravind, L.] NIH, Natl Ctr Biotechnol Informat, Natl Lib Med, Bethesda, MD 20894 USA. [Hench, Virginia K.; Frazier-Bowers, Sylvia A.; Pukkila, Patricia J.] Univ N Carolina, Dept Biol, Chapel Hill, NC 27599 USA. [Korol, Evgenia; Tahiliani, Mamta] NYU, Langone Med Ctr, Skirball Inst, New York, NY 10016 USA. [Liu, Shuo; Wang, Yinsheng] Univ Calif Riverside, Environm Toxicol Grad Program, Riverside, CA 92521 USA. [Liu, Shuo; Wang, Yinsheng] Univ Calif Riverside, Dept Chem, Riverside, CA 92521 USA. [Rao, Anjana] Univ Calif San Diego, Dept Pharmacol, San Diego, CA 92093 USA. [Rao, Anjana] Univ Calif San Diego, Moores Canc Ctr, San Diego, CA 92093 USA. RP Rao, A (reprint author), La Jolla Inst Allergy & Immunol, Div Signaling & Gene Express, La Jolla, CA 92037 USA. EM arao@liai.org OI Huang, Yun/0000-0001-5950-9168; Chavez, Lukas/0000-0002-8718-8848 FU NIH [R01 HD065812, R01 AI44432, R01 CA151535, K08 HL089150, R01 CA101864]; California Institute for Regenerative Medicine Grant [RM1-01729]; Leukemia Society of America Translational Research Program [6187-12]; Howard Hughes Medical Institute through the Undergraduate Science Education Program; Harvard Catalyst; Harvard Clinical and Translational Science Center [NIH] [1 UL1 RR 025758-02]; Leukemia and Lymphoma Society; National Science Foundation; Feodor Lynen Research Fellowship from the Alexander von Humboldt Foundation; National Library of Medicine, NIH FX This work was supported by NIH Grants R01 HD065812 (to A.R.), R01 AI44432 (to A.R.), R01 CA151535 (to A.R.), K08 HL089150 (to S.A.), and R01 CA101864 (to Y.W.); California Institute for Regenerative Medicine Grant RM1-01729 (to A.R.); Leukemia Society of America Translational Research Program Award 6187-12 (to A.R.); a grant to University of North Carolina Chapel Hill from the Howard Hughes Medical Institute through the Undergraduate Science Education Program (to P.J.P.); a pilot grant from Harvard Catalyst, the Harvard Clinical and Translational Science Center [NIH Grant 1 UL1 RR 025758-02 (to S.A.)]; a postdoctoral fellowship from the Leukemia and Lymphoma Society (to Y.H.); a predoctoral fellowship from the National Science Foundation (to W.A.P.); a Feodor Lynen Research Fellowship from the Alexander von Humboldt Foundation (to L.C.); and intramural funds of the National Library of Medicine, NIH (L.A. and L.M.I.). NR 52 TC 4 Z9 4 U1 5 U2 28 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD DEC 2 PY 2014 VL 111 IS 48 BP E5149 EP E5158 DI 10.1073/pnas.1419513111 PG 10 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA AU9NN UT WOS:000345920800004 PM 25406324 ER PT J AU Chen, J Grunwald, D Sardo, L Galli, A Plisov, S Nikolaitchik, OA Chen, D Lockett, S Larson, DR Pathak, VK Hu, WS AF Chen, Jianbo Grunwald, David Sardo, Luca Galli, Andrea Plisov, Sergey Nikolaitchik, Olga A. Chen, De Lockett, Stephen Larson, Daniel R. Pathak, Vinay K. Hu, Wei-Shau TI Cytoplasmic HIV-1 RNA is mainly transported by diffusion in the presence or absence of Gag protein SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE HIV-1; RNA; transport; cytoplasm; diffusion ID ACTIN MESSENGER-RNA; NUCLEAR EXPORT ELEMENTS; LIVING CELLS; ENDOSOMAL TRAFFICKING; MAMMALIAN-CELLS; BINDING PROTEIN; GENOMIC RNAS; DYNAMICS; VISUALIZATION; CYTOSKELETAL AB Full-length HIV-1 RNA plays a central role in viral replication by serving as the mRNA for essential viral proteins and as the genome packaged into infectious virions. Proper RNA trafficking is required for the functions of RNA and its encoded proteins; however, the mechanism by which HIV-1 RNA is transported within the cytoplasm remains undefined. Full-length HIV-1 RNA transport is further complicated when group-specific antigen (Gag) protein is expressed, because a significant portion of HIV-1 RNA may be transported as Gag-RNA complexes, whose properties could differ greatly from Gag-free RNA. In this report, we visualized HIV-1 RNA and monitored its movement in the cytoplasm by using single-molecule tracking. We observed that most of the HIV-1 RNA molecules move in a nondirectional, random-walk manner, which does not require an intact cytoskeletal structure, and that the mean-squared distance traveled by the RNA increases linearly with time, indicative of diffusive movement. We also observed that a single HIV-1 RNA molecule can move at various speeds when traveling through the cytoplasm, indicating that its movement is strongly affected by the immediate environment. To examine the effect of Gag protein on HIV-1 RNA transport, we analyzed the cytoplasmic HIV-1 RNA movement in the presence of sufficient Gag for virion assembly and found that HIV-1 RNA is still transported by diffusion with mobility similar to the mobility of RNAs unable to express functional Gag. These studies define a major mechanism of HIV-1 gene expression and resolve the long-standing question of how the RNA genome is transported to the assembly site. C1 [Chen, Jianbo; Sardo, Luca; Galli, Andrea; Plisov, Sergey; Nikolaitchik, Olga A.; Hu, Wei-Shau] NCI, Viral Recombinat Sect, Ctr Canc Res, Frederick, MD 21702 USA. [Pathak, Vinay K.] NCI, Viral Mutat Sect, HIV Drug Resistance Program, Ctr Canc Res, Frederick, MD 21702 USA. [Grunwald, David] Univ Massachusetts, Sch Med, RNA Therapeut Inst, Worcester, MA 01605 USA. [Grunwald, David] Univ Massachusetts, Sch Med, Dept Biochem & Mol Pharmacol, Worcester, MA 01605 USA. [Chen, De; Lockett, Stephen] Leidos Biomed Res Inc, Opt Microscopy & Anal Lab, Frederick Natl Lab Canc Res, Ft Detrick, MD 21702 USA. [Larson, Daniel R.] NCI, Lab Receptor Biol & Gene Express, Bethesda, MD 20892 USA. RP Hu, WS (reprint author), NCI, Viral Recombinat Sect, Ctr Canc Res, Frederick, MD 21702 USA. EM Wei-Shau.Hu@nih.gov RI Larson, Daniel/B-9829-2008; OI Larson, Daniel/0000-0001-9253-3055; Galli, Andrea/0000-0002-4404-430X FU Intramural Research Program of the NIH, National Cancer Institute (NCI), Center for Cancer Research; NCI, NIH [HHSN261200800001E]; Intramural AIDS Targeted Antiviral Program grant funding FX We thank Anne Arthur for expert editorial help; Drs. Steve Hughes, Eric Freed, John Coffin, and Alan Rein and Ryan Burdick for discussions and critical reading of the manuscript; and Dr. Joseph Brzostowski for providing the MATLAB tracking program. This research was supported, in part, by the Intramural Research Program of the NIH, National Cancer Institute (NCI), Center for Cancer Research; by federal funds from the NCI, NIH, under Contract HHSN261200800001E; and by Intramural AIDS Targeted Antiviral Program grant funding (to W.-S.H. and to V.K.P.). NR 45 TC 20 Z9 20 U1 1 U2 12 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD DEC 2 PY 2014 VL 111 IS 48 BP E5205 EP E5213 DI 10.1073/pnas.1413169111 PG 9 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA AU9NN UT WOS:000345920800010 PM 25404326 ER PT J AU Cero, C Vostrikov, VV Verardi, R Severini, C Gopinath, T Braun, PD Sassano, MF Gurney, A Roth, BL Vulchanova, L Possenti, R Veglia, G Bartolomucci, A AF Cero, Cheryl Vostrikov, Vitaly V. Verardi, Raffaello Severini, Cinzia Gopinath, Tata Braun, Patrick D. Sassano, Maria F. Gurney, Allison Roth, Bryan L. Vulchanova, Lucy Possenti, Roberta Veglia, Gianluigi Bartolomucci, Alessandro TI The TLQP-21 Peptide Activates the G-Protein-Coupled Receptor C3aR1 via a Folding-upon-Binding Mechanism SO STRUCTURE LA English DT Article ID VGF-DERIVED PEPTIDE; DIET-INDUCED OBESITY; CLASS-B GPCRS; ADIPOSE-TISSUE; IN-VITRO; IDENTIFICATION; COMPLEMENT; NMR; ANAPHYLATOXIN; RECOGNITION AB TLQP-21, a VGF-encoded peptide is emerging as a novel target for obesity-associated disorders. TLQP-21 is found in the sympathetic nerve terminals in the adipose tissue and targets the G-protein-coupled receptor complement-3a receptor1 (C3aR1). The mechanisms of TLQP-21-induced receptor activation remain unexplored. Here, we report that TLQP-21 is intrinsically disordered and undergoes a disorder-to-order transition, adopting an alpha-helical conformation upon targeting cells expressing the C3aR1. We determined that the hot spots for TLQP-21 are located at the Cterminus, with mutations in the last four amino acids progressively reducing the bioactivity and, a single site mutation (R21A) or C-terminal amidation abolishing its function completely. Additionally, the human TLQP-21 sequence carrying a S20A substitution activates the human C3aR1 receptor with lower potency compared to the rodent sequence. These studies reveal the mechanism of action of TLQP-21 and provide molecular templates for designing agonists and antagonists to modulate C3aR1 functions. C1 [Cero, Cheryl; Gurney, Allison; Bartolomucci, Alessandro] Univ Minnesota, Dept Integrat Biol & Physiol, Minneapolis, MN 55455 USA. [Vostrikov, Vitaly V.; Verardi, Raffaello; Gopinath, Tata; Veglia, Gianluigi] Univ Minnesota, Dept Biochem Mol Biol & Biophys, Minneapolis, MN 55455 USA. [Severini, Cinzia; Possenti, Roberta] CNR, Inst Cell Biol & Neurobiol, I-00143 Rome, Italy. [Braun, Patrick D.] Univ Minnesota, Dept Pharmaceut, Minneapolis, MN 55455 USA. [Sassano, Maria F.; Roth, Bryan L.] Univ N Carolina, Sch Med, Dept Pharmacol, Chapel Hill, NC 27599 USA. [Sassano, Maria F.; Roth, Bryan L.] Univ N Carolina, Sch Med, NIMH, Psychoact Drug Screening Program, Chapel Hill, NC 27599 USA. [Possenti, Roberta] Univ Roma Tor Vergata, Dept Med Syst, I-00133 Rome, Italy. [Vulchanova, Lucy] Univ Minnesota, Dept Neurosci, Minneapolis, MN 55455 USA. RP Veglia, G (reprint author), Univ Minnesota, Dept Biochem Mol Biol & Biophys, Minneapolis, MN 55455 USA. EM vegli001@umn.edu; abartolo@umn.edu RI Roth, Bryan/F-3928-2010; OI Vulchanova, Lucy/0000-0002-6577-4467 FU Minnesota Partnership for Biotechnology and Medical Genomic, Decade of Discovery in Diabetes Grant [NIH/DK102496, NIH R01DE021996, NIH R21DA025170]; NIMH Psychoactive Drug Screening Program FX Supported by the Minnesota Partnership for Biotechnology and Medical Genomic, Decade of Discovery in Diabetes Grant (to A.B.), NIH/DK102496 (to A.B.), NIH R01DE021996 and NIH R21DA025170 (to L.V.), and the NIMH Psychoactive Drug Screening Program (to B.L.R. and M. F.S.). NMR experiments were carried out at the Minnesota NMR Center. 3T3L1 cells were provided by The Molecular & Cellular Basis of Obesity Core, Minnesota Obesity Center (P30 DK050456). We thank D. Piomelli, G. Bottegoni, W. Rocchia, A. Lodola, and M. Mor for important suggestions in various stages of the study, and I. Ninkovich, P. Petrocchi, and M. Razzoli for technical help. NR 56 TC 10 Z9 10 U1 0 U2 6 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 0969-2126 EI 1878-4186 J9 STRUCTURE JI Structure PD DEC 2 PY 2014 VL 22 IS 12 BP 1744 EP 1753 DI 10.1016/j.str.2014.10.001 PG 10 WC Biochemistry & Molecular Biology; Biophysics; Cell Biology SC Biochemistry & Molecular Biology; Biophysics; Cell Biology GA AU9GC UT WOS:000345898700008 PM 25456411 ER PT J AU Gabel, SA Smith, CE Cuneo, MJ Mueller, GA Kirby, TW DeRose, EF Krahn, JM London, RE AF Gabel, Scott A. Smith, Cassandra E. Cuneo, Matthew J. Mueller, Geoffrey A. Kirby, Thomas W. DeRose, Eugene F. Krahn, Juno M. London, Robert E. TI Characterization of the Redox Transition of the XRCC1 N-terminal Domain SO STRUCTURE LA English DT Article ID STRAND-BREAK REPAIR; PROTEIN DISULFIDE-ISOMERASE; NUCLEAR-MAGNETIC-RESONANCE; DNA-POLYMERASE-BETA; CARBAMINO ADDUCT FORMATION; SIDE-CHAIN RESONANCES; BASE EXCISION-REPAIR; NMR CHEMICAL-SHIFTS; BOND FORMATION; AMINO-ACIDS AB XRCC1, a scaffold protein involved in DNA repair, contains an N-terminal domain (X1NTD) that interacts specifically with DNA polymerase beta. It was recently discovered that X1NTD contains a disulfide switch that allows it to adopt either of two metamorphic structures. In the present study, we demonstrate that formation of an N-terminal proline carbimate adduct resulting from the nonenzymatic reaction of Pro2 with CO2 is essential for stabilizing the oxidized structure, X1NTDox. The kinetic response of X1NTDred to H2O2, monitored by NMR, was determined to be very slow, consistent with involvement of the buried, kinetically trapped Cys12 residue, but was significantly accelerated by addition of protein disulfide isomerase or by Cu2+. NMR analysis of a sample containing the pol beta polymerase domain, and both the reduced and oxidized forms of X1NTD, indicates that the oxidized form binds to the enzyme 25-fold more tightly than the reduced form. C1 [Gabel, Scott A.; Smith, Cassandra E.; Cuneo, Matthew J.; Mueller, Geoffrey A.; Kirby, Thomas W.; DeRose, Eugene F.; Krahn, Juno M.; London, Robert E.] NIEHS, Struct Biol Lab, NIH, Res Triangle Pk, NC 27709 USA. RP London, RE (reprint author), NIEHS, Struct Biol Lab, NIH, POB 12233, Res Triangle Pk, NC 27709 USA. EM london@niehs.nih.gov OI Cuneo, Matthew/0000-0002-1475-6656 FU Intramural Research Program of the NIH; National Institute of Environmental Health Sciences (NIEHS) [Z01-ES050111, HHSN273200700046U]; NIH FX This research was supported by the Intramural Research Program of the NIH and National Institute of Environmental Health Sciences (NIEHS) under Research Project Number Z01-ES050111 to R.E.L. E.F.D. is supported by the NIH and NIEHS under delivery order HHSN273200700046U. NR 49 TC 2 Z9 2 U1 0 U2 6 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 0969-2126 EI 1878-4186 J9 STRUCTURE JI Structure PD DEC 2 PY 2014 VL 22 IS 12 BP 1754 EP 1763 DI 10.1016/j.str.2014.09.012 PG 10 WC Biochemistry & Molecular Biology; Biophysics; Cell Biology SC Biochemistry & Molecular Biology; Biophysics; Cell Biology GA AU9GC UT WOS:000345898700009 PM 25456813 ER PT J AU Lemak, A Wu, B Yee, A Houliston, S Lee, HW Gutmanas, A Fang, XY Garcia, M Semesi, A Wang, YX Prestegard, JH Arrowsmith, CH AF Lemak, Alexander Wu, Bin Yee, Adelinda Houliston, Scott Lee, Hsiau-Wei Gutmanas, Aleksandras Fang, Xianyang Garcia, Maite Semesi, Anthony Wang, Yun-Xing Prestegard, James H. Arrowsmith, Cheryl H. TI Structural Characterization of a Flexible Two-Domain Protein in Solution Using Small Angle X-Ray Scattering and NMR Data SO STRUCTURE LA English DT Article ID RESIDUAL DIPOLAR COUPLINGS; ENSEMBLE REFINEMENT; 3-WAY DECOMPOSITION; COMBINING NMR; RESTRAINTS; RELAXATION; ASSIGNMENT; PREDICTION; ALIGNMENT; SOFTWARE AB Multidomain proteins in which individual domains are connected by linkers often possess inherent interdomain flexibility that significantly complicates their structural characterization in solution using either nuclear magnetic resonance (NMR) spectroscopy or small-angle X-ray scattering (SAXS) alone. Here, we report a protocol for joint refinement of flexible multidomain protein structures against NMR distance and angular restraints, residual dipolar couplings, and SAXS data. The protocol is based on the ensemble optimization method principle (Bernado et al., 2007) and is compared with different refinement strategies for the structural characterization of the flexible two-domain protein sf3636 from Shigella flexneri 2a. The results of our refinement suggest the existence of a dominant population of configurational states in solution possessing an overall elongated shape and restricted relative twisting of the two domains. C1 [Lemak, Alexander; Wu, Bin; Yee, Adelinda; Houliston, Scott; Gutmanas, Aleksandras; Garcia, Maite; Semesi, Anthony; Arrowsmith, Cheryl H.] Princess Margaret Canc Ctr, Toronto, ON M5G 2M9, Canada. [Lemak, Alexander; Wu, Bin; Yee, Adelinda; Houliston, Scott; Gutmanas, Aleksandras; Garcia, Maite; Semesi, Anthony; Arrowsmith, Cheryl H.] Univ Toronto, Dept Med Biophys, Toronto, ON M5G 2M9, Canada. [Lee, Hsiau-Wei; Prestegard, James H.] Univ Georgia, Complex Carbohydrate Res Ctr, Athens, GA 30602 USA. [Fang, Xianyang; Wang, Yun-Xing] NCI, Prot Nucle Acid Interact Sect, Struct Biophys Lab, NIH, Frederick, MD 21702 USA. RP Arrowsmith, CH (reprint author), Princess Margaret Canc Ctr, Toronto, ON M5G 2M9, Canada. EM carrow@uhnresearch.ca OI Gutmanas, Aleksandras/0000-0001-6311-0176 FU NIH Protein Structure Initiative grant [U54 GM094597]; Natural Sciences and Engineering Research Council of Canada; Canadian Institute of Health Research through Canada Research Chairs program FX This work was supported by NIH Protein Structure Initiative grant U54 GM094597, the Natural Sciences and Engineering Research Council of Canada, and the Canadian Institute of Health Research through the Canada Research Chairs program (to C.H.A.). A.L., B.W., A.Y., S.H., H.-W.L., A.G., M.G., A.S., J.H.P., and C.H.A. are participants in the Northeast Structural Genomics Consortium. NR 38 TC 2 Z9 2 U1 2 U2 20 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 0969-2126 EI 1878-4186 J9 STRUCTURE JI Structure PD DEC 2 PY 2014 VL 22 IS 12 BP 1862 EP 1874 DI 10.1016/j.str.2014.09.013 PG 13 WC Biochemistry & Molecular Biology; Biophysics; Cell Biology SC Biochemistry & Molecular Biology; Biophysics; Cell Biology GA AU9GC UT WOS:000345898700019 PM 25456817 ER PT J AU Opal, SM Dellinger, RP Vincent, JL Masur, H Angus, DC AF Opal, Steven M. Dellinger, R. Phillip Vincent, Jean-Louis Masur, Henry Angus, Derek C. TI Addressing the Global Burden of Sepsis: Importance of a Systems-Based Approach Reply SO CRITICAL CARE MEDICINE LA English DT Letter C1 [Opal, Steven M.] Brown Univ, Alpert Med Sch, Div Infect Dis, Providence, RI 02912 USA. [Dellinger, R. Phillip] Rowan Univ, Cooper Med Sch, Camden, NJ USA. [Vincent, Jean-Louis] Erasme Univ Hosp, Dept Intens Care, B-1070 Brussels, Belgium. [Masur, Henry] NIH, Bethesda, MD 20892 USA. [Angus, Derek C.] Univ Pittsburgh, Sch Med, Pittsburgh, PA USA. RP Opal, SM (reprint author), Brown Univ, Alpert Med Sch, Div Infect Dis, Providence, RI 02912 USA. NR 7 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 0090-3493 EI 1530-0293 J9 CRIT CARE MED JI Crit. Care Med. PD DEC PY 2014 VL 42 IS 12 BP E798 EP E799 DI 10.1097/CCM.0000000000000681 PG 3 WC Critical Care Medicine SC General & Internal Medicine GA CS4XX UT WOS:000362080700011 PM 25402303 ER PT J AU Minniti, CP Gorbach, AM Xu, DH Hon, YY Delaney, KM Seidel, M Malik, N Peters-Lawrence, M Cantilena, C Nichols, JS Mendelsohn, L Conrey, A Grimes, G Kato, GJ AF Minniti, Caterina P. Gorbach, Alexander M. Xu, Dihua Hon, Yuen Yi Delaney, Kara-Marie Seidel, Miles Malik, Nitin Peters-Lawrence, Marlene Cantilena, Carly Nichols, James S. Mendelsohn, Laurel Conrey, Anna Grimes, George Kato, Gregory J. TI Topical sodium nitrite for chronic leg ulcers in patients with sickle cell anaemia: a phase 1 dose-finding safety and tolerability trial SO LANCET HAEMATOLOGY LA English DT Article ID REGIONAL BLOOD-FLOW; WOUND REPAIR; OXIDE; DISEASE; HUMANS; PHARMACOKINETICS; FORMULATIONS; HYDROXYUREA; MECHANISMS; ULCERATION AB Background Well-tolerated and effective treatments are needed for chronic leg ulcers in sickle cell anaemia. Topical sodium nitrite, a known nitric oxide donor, enhances blood flow in ulcers and has known bacteriostatic effects. We aimed to assess the safety, tolerability, and pharmacokinetics of topical sodium nitrite in patients with sickle cell disease and chronic leg ulcers. Methods We enrolled adult patients from an ambulatory clinic at the National Institutes of Health (Bethesda, MD, USA) with sickle cell anaemia with leg ulcers (with a surface area of 2.5-100 cm(2)) persisting for at least 4 weeks into a safety and tolerability phase 1 dose-escalation trial of topical sodium nitrite. Increasing concentrations of sodium nitrite cream were applied twice weekly for 4 weeks to one ulcer per patient at five dose levels (0.5%, 1%, 1.5%, 1.8%, and 2%). The primary endpoints were safety and tolerability, with secondary endpoints of pharmacokinetics, blood flow, and wound healing. Pain relief was analysed post hoc. Endpoints were analysed over time for the whole study population and according to dose level. This study is registered with ClinicalTrials.gov, number NCT01316796. Findings Between April 4, 2011, and March 19, 2013, we enrolled 18 adult patients with sickle cell anaemia and leg ulcers into our trial. We assigned three patients into each cohort, and each cohort was treated with a different concentration of sodium nitrite cream (cohort 1: 0.5%, cohort 2: 1.0%, cohort 3: 1.5%, and cohort 4: 2.0%). Patients were not enrolled into the next cohort dose until we were able to establish that no dose-limiting toxicities were observed. An additional six patients were enrolled to cohort 3a: 1.8%, after two patients in cohort 4 had asymptomatic drops in diastolic blood pressure. No grade 3-4 adverse events were observed, and there were no serious adverse events or dose-limiting side-effects. Pharmacokinetic analysis showed that systemic absorption of sodium nitrite was very low. Application of topical sodium nitrite was associated with a significant increase in peri-wound cutaneous blood flow measured by laser speckle contrast imaging (p=0.0002), corroborated by increased peri-wound skin temperature by infrared thermography (p=0.0119). We recorded a dose-dependent decrease in leg ulcer size (p=0.0012) and pain (p<0.0001). Ulcers healed completely in three patients who received the highest concentrations of topical sodium nitrite (the 1.8% and 2% cream). In our post-hoc analysis of pain, brief pain inventory scores improved in pain severity (p=0.0048) and pain interference (p=0.0013). Interpretation Our results indicate that topical sodium nitrite 2% cream is suitable for additional clinical trials in adults with sickle cell anaemia to promote healing of leg ulcers. C1 [Minniti, Caterina P.; Delaney, Kara-Marie; Peters-Lawrence, Marlene; Cantilena, Carly; Nichols, James S.; Mendelsohn, Laurel; Conrey, Anna; Kato, Gregory J.] NHLBI, NIH, Bethesda, MD 20892 USA. [Hon, Yuen Yi; Grimes, George] NIH, Pharmaceut Dev Serv, Clin Ctr Pharm Dept, Bethesda, MD 20892 USA. [Gorbach, Alexander M.; Seidel, Miles; Malik, Nitin] Natl Inst Biomed Imaging & Bioengn, Infrared & Thermometry Unit, NIH, Bethesda, MD 20892 USA. [Kato, Gregory J.] Univ Pittsburgh, Dept Med, Pittsburgh, PA USA. RP Kato, GJ (reprint author), Univ Pittsburgh, Dept Med, Div Hematol Oncol, 200 Lothrop St,BST E1240, Pittsburgh, PA 15261 USA. EM katogj@upmc.edu RI Kato, Gregory/I-7615-2014 OI Kato, Gregory/0000-0003-4465-3217 FU National Heart, Lung and Blood Institute Division [1 ZIA HL006127-01] FX This study was funded by the National Heart, Lung and Blood Institute Division of Intramural Research (grant 1 ZIA HL006127-01). We thank Vince Williams and Adriana Byrnes for expert protocol management; Karen Axelrod and Ashley Buscetta for expert wound care; Chaitali Patel for pharmacy support; Emily Moldiz and Brigit Sullivan (National Institutes of Health Library Writing Center) for editorial assistance; and all the patients who participated in this study. NR 41 TC 8 Z9 8 U1 0 U2 2 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 2352-3026 J9 LANCET HAEMATOL JI Lancet Haematol. PD DEC PY 2014 VL 1 IS 3 BP E95 EP E103 DI 10.1016/S2352-3026(14)00019-2 PG 9 WC Hematology SC Hematology GA CS4UE UT WOS:000362070600006 PM 25938131 ER PT J AU El Meskini, R Iacovelli, A Kulaga, A Gumprecht, M Martin, P Baran, M Householder, D van Dyke, T Ohler, ZW AF El Meskini, Rajaa Iacovelli, Anthony Kulaga, Alan Gumprecht, Michelle Martin, Philip Baran, Maureen Householder, Deborah van Dyke, Terry Ohler, Zoe Weaver TI Synergistic control of GBM growth by MEK and PI3kinase signaling in a RAS-driven preclinical orthotopic model for human glioblastoma multiforme SO MOLECULAR CANCER RESEARCH LA English DT Meeting Abstract CT AACR Special Conference on RAS Oncogenes - From Biology to Therapy CY FEB 24-27, 2014 CL Lake Buena Vista, FL SP Amer Assoc Canc Res C1 [El Meskini, Rajaa; Iacovelli, Anthony; Kulaga, Alan; Gumprecht, Michelle; Martin, Philip; Baran, Maureen; Ohler, Zoe Weaver] Leidos Biomed Res Inc, Frederick, MD USA. [Householder, Deborah; van Dyke, Terry] Frederick Natl Lab Canc Res, Frederick, MD USA. NR 0 TC 0 Z9 0 U1 3 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 SU 12 MA B03 DI 10.1158/1557-3125.RASONC14-B03 PG 1 WC Oncology; Cell Biology SC Oncology; Cell Biology GA CQ9IZ UT WOS:000360929000053 ER PT J AU Lee, S Basu, SK Walia, V Morrison, DK Johnson, PF AF Lee, Sook Basu, Sandip K. Walia, Vijay Morrison, Deborah K. Johnson, Peter F. TI Oncogenic Ras signaling involves sustained perinuclear localization of the effector kinases p-ERK1/2 and CK2 via KSR-1 and endosomal trafficking SO MOLECULAR CANCER RESEARCH LA English DT Meeting Abstract CT AACR Special Conference on RAS Oncogenes - From Biology to Therapy CY FEB 24-27, 2014 CL Lake Buena Vista, FL SP Amer Assoc Canc Res C1 [Lee, Sook; Basu, Sandip K.; Johnson, Peter F.] NCI Frederick, Ctr Canc Res, Mouse Canc Genet Program, Frederick, MD USA. [Walia, Vijay; Morrison, Deborah K.] NCI Frederick, Ctr Canc Res, Lab Cell & Dev Signaling, Frederick, MD USA. NR 0 TC 0 Z9 0 U1 4 U2 4 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 SU 12 MA A11 DI 10.1158/1557-3125.RASONC14-A11 PG 1 WC Oncology; Cell Biology SC Oncology; Cell Biology GA CQ9IZ UT WOS:000360929000011 ER PT J AU Salotti, J Sakchaisri, K Johnson, PF AF Salotti, Jacqueline Sakchaisri, Krisada Johnson, Peter F. TI A Ras-Arf-Egr-C/EBP beta axis underlying oncogene-induced senescence and cancer SO MOLECULAR CANCER RESEARCH LA English DT Meeting Abstract CT AACR Special Conference on RAS Oncogenes - From Biology to Therapy CY FEB 24-27, 2014 CL Lake Buena Vista, FL SP Amer Assoc Canc Res C1 [Salotti, Jacqueline; Sakchaisri, Krisada; Johnson, Peter F.] NCI Frederick, Mouse Canc Genet Program, Ctr Canc Res, Frederick, MD USA. NR 0 TC 0 Z9 0 U1 3 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 SU 12 MA A19 DI 10.1158/1557-3125.RASONC14-A19 PG 1 WC Oncology; Cell Biology SC Oncology; Cell Biology GA CQ9IZ UT WOS:000360929000018 ER PT J AU Yu, B Swatkoski, S Holly, A Lee, LC Giroux, V Lee, CS Carver, J Creighton, C Ann, DK Figg, WD Gucek, M Luo, J AF Yu, Bing Swatkoski, Steve Holly, Alesia Lee, Liam Changwoo Giroux, Valentin Lee, Chih-Shia Carver, Joseph Creighton, Chad Ann, David K. Figg, William Douglas Gucek, Marjan Luo, Ji TI A critical role of the SUMO pathway in KRAS-driven oncogenesis SO MOLECULAR CANCER RESEARCH LA English DT Meeting Abstract CT AACR Special Conference on RAS Oncogenes - From Biology to Therapy CY FEB 24-27, 2014 CL Lake Buena Vista, FL SP Amer Assoc Canc Res C1 [Yu, Bing; Holly, Alesia; Lee, Liam Changwoo; Giroux, Valentin; Lee, Chih-Shia; Carver, Joseph; Figg, William Douglas; Luo, Ji] NCI, Canc Res Ctr, Bethesda, MD 20892 USA. [Swatkoski, Steve; Gucek, Marjan] NHLBI, Bethesda, MD 20892 USA. [Creighton, Chad] Baylor Coll Med, Houston, TX 77030 USA. [Ann, David K.] Beckman Res Inst City Hope, Duarte, CA USA. RI Figg Sr, William/M-2411-2016 NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1541-7786 EI 1557-3125 J9 MOL CANCER RES JI Mol. Cancer Res. PD DEC PY 2014 VL 12 SU 12 MA B29 DI 10.1158/1557-3125.RASONC14-B29 PG 1 WC Oncology; Cell Biology SC Oncology; Cell Biology GA CQ9IZ UT WOS:000360929000071 ER PT J AU Dongworth, RK Campbell-Washburn, AE Roberts, T Yellon, DM Lythgoe, MF Hausenloy, DJ AF Dongworth, R. K. Campbell-Washburn, A. E. Roberts, T. Yellon, D. M. Lythgoe, M. F. Hausenloy, D. J. TI CARDIAC ARTERIAL SPIN LABELLING MRI AS A NOVEL APPROACH FOR IN VIVO QUANTIFICATION OF THE AREA-AT-RISK SO HEART LA English DT Meeting Abstract CT Autumn Meeting of the British-Society-for-Cardiovascular-Research (BSCR) on Cardiovascular Signalling in Health and Disease CY SEP 08-09, 2014 CL Univ Reading, Reading, ENGLAND SP British Soc Cardiovascular Res HO Univ Reading C1 [Dongworth, R. K.; Yellon, D. M.; Hausenloy, D. J.] UCL, Hatter Cardiovasc Inst, London WC1E 6BT, England. [Campbell-Washburn, A. E.; Roberts, T.; Lythgoe, M. F.] UCL, Ctr Adv Biomed Imaging, London WC1E 6BT, England. [Campbell-Washburn, A. E.] NHLBI, Div Intramural Res, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU BMJ PUBLISHING GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 1355-6037 EI 1468-201X J9 HEART JI Heart PD DEC PY 2014 VL 100 SU 4 MA 055 DI 10.1136/heartjnl-2014-306916.55 PG 2 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA CP6MF UT WOS:000360000800056 ER PT J AU Haverkos, L Esposito, L AF Haverkos, Lynne Esposito, Layla TI News from the NIH: Diversity, disparities, and disabilities research SO TRANSLATIONAL BEHAVIORAL MEDICINE LA English DT News Item C1 [Haverkos, Lynne; Esposito, Layla] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Bethesda, MD 20892 USA. RP Esposito, L (reprint author), Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Bethesda, MD 20892 USA. EM espositl@mail.nih.gov NR 3 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER INTERNATIONAL PUBLISHING AG PI CHAM PA GEWERBESTRASSE 11, CHAM, CH-6330, SWITZERLAND SN 1869-6716 EI 1613-9860 J9 TRANSL BEHAV MED JI Transl. Behav. Med. PD DEC PY 2014 VL 4 IS 4 BP 339 EP 341 DI 10.1007/s13142-014-0271-2 PG 3 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA CL2PR UT WOS:000356787000001 PM 25584081 ER PT J AU Bellgard, MI Sleeman, MW Guerrero, FD Fletcher, S Baynam, G Goldblatt, J Rubinstein, Y Bell, C Groft, S Barrero, R Bittles, AH Wilton, SD Mason, CE Weeramanthri, T AF Bellgard, Matthew I. Sleeman, Mark W. Guerrero, Felix D. Fletcher, Sue Baynam, Gareth Goldblatt, Jack Rubinstein, Yaffa Bell, Callum Groft, Stephen Barrero, Roberto Bittles, Alan H. Wilton, Stephen D. Mason, Christopher E. Weeramanthri, Tarun TI Rare Disease Research Roadmap: Navigating the bioinformatics and translational challenges for improved patient health outcomes SO HEALTH POLICY AND TECHNOLOGY LA English DT Article DE Rare disease; Bioinformatics; Translational research ID DUCHENNE MUSCULAR-DYSTROPHY; GENETIC-VARIATION; REGISTRY; PHENOTYPES; THERAPY AB Rare disease registries have now been recognized as a global priority for progress both in monitoring and documenting the natural course, and preventing and treating rare diseases. However, a disease registry is only one element of rare disease translational research. Here, we outline what we believe are ten key components in comprehensive rare disease translational research and describe critical relationships between them. These components are: (i) client-practitioner partnerships; (ii) disease registries; (iii) biobanks; (iv) genomics and other -omics platforms; (v) community-based and population-wide studies; (vi) bioinformatics and high performance computing; (vii) interactions with pharma to facilitate drug discovery; (viii) personalized treatments based on genotype-phenotype correlations; (ix) eHealth and a whole of life record; and (x) regulatory frameworks, particularly with regard to specimen and data sharing, and the return of results. Each component has its own inherent complexity, but if effectively integrated they will provide a comprehensive approach to the future management of rare diseases, and aid health care providers in delivering services to individuals affected with rare diseases. We demonstrate that navigation through the roadmap can provide relevant health stakeholders with a blueprint to understand the challenges and barriers which need to be overcome within and across the constituent components. The rare disease roadmap will assist decision-making at all health stakeholder levels and enable the seamless integration of new knowledge, standard operating procedures and the implementation of best practice. (C) 2014 Fellowship of Postgraduate Medicine. Published by Elsevier Ltd. All rights reserved. C1 [Bellgard, Matthew I.; Fletcher, Sue; Barrero, Roberto; Bittles, Alan H.; Wilton, Stephen D.] Murdoch Univ, Ctr Comparat Gen, Perth, WA, Australia. [Bellgard, Matthew I.; Bell, Callum] Natl Ctr Genome Resources, Santa Fe, NM USA. [Sleeman, Mark W.] Monash Univ, Dept Physiol Biochem & Mol Biol, Clayton, Vic 3800, Australia. [Guerrero, Felix D.] ARS, US Dept Agr, Knipling Bushland, US Livestock Insects Res Lab, Kerrville, TX USA. [Fletcher, Sue; Wilton, Stephen D.] Univ Western Australia, Western Australian Neurosci Res Inst, Nedlands, WA 6009, Australia. [Fletcher, Sue; Wilton, Stephen D.] Univ Western Australia, Ctr Neuromuscular & Neurol Disorders, Nedlands, WA 6009, Australia. [Baynam, Gareth] King Edward Mem Hosp, Genet Serv Western Australia, Perth, WA, Australia. [Baynam, Gareth] Off Populat Hlth Genom, Publ Hlth & Clin Serv Div, Dept Hlth, Nedlands, WA, Australia. [Baynam, Gareth] Univ Western Australia, Sch Paediat & Child Hlth, Perth, WA 6009, Australia. [Baynam, Gareth] Murdoch Univ, lnst Immunol & Infect Dis, Perth, WA, Australia. [Goldblatt, Jack] Genet Serv & Familial Canc Program Western Austra, Subiaco, WA, Australia. [Rubinstein, Yaffa; Groft, Stephen] Natl Ctr Adv Translat Sci, NIH, Off Rare Dis Res, Bethesda, MD USA. [Bittles, Alan H.] Edith Cowan Univ, Sch Med Sci, Community Genet, Churchlands, WA 6018, Australia. [Mason, Christopher E.] Weill Cornell Med Coll, Dept Physiol & Biophys, New York, NY USA. [Mason, Christopher E.] Weill Cornell Med Coll, HRH Prince Alwaleed Bin Talal Bin Abdulaziz Alsau, New York, NY USA. [Mason, Christopher E.] Weill Cornell Med Coll, Feil Family Brain & Mind Res Inst, New York, NY USA. [Weeramanthri, Tarun] Western Australia Dept Hlth, Publ Hlth & Clin Serv Div, Perth, WA, Australia. RP Bellgard, MI (reprint author), Murdoch Univ, Ctr Comparat Gen, Perth, WA, Australia. EM mbellgard@ccg.murdoch.edu.au OI Bittles, Alan/0000-0002-8176-2730; Fletcher, Sue/0000-0002-8632-641X FU Australian National Health and Medical Research Council [APP634485, APP1055319]; EU FP7 Project [HEALTH.2012.2.1.1-1-C]; United States Department of Agriculture, Agriculture Research Service [CRIS 6205-32000-031]; OECD Co-operative Research Programme: Biological Resource Management for Sustainable Agriculture Systems FX The authors received funding from the Australian National Health and Medical Research Council (APP634485, APP1055319) and EU FP7 Project (HEALTH.2012.2.1.1-1-C): RD Connect: An integrated platform connecting databases, registries, biobanks and clinical bioinformatics for rare disease research. F. Guerrero received funding from United States Department of Agriculture, Agriculture Research Service Project No. CRIS 6205-32000-031. USDA is an equal opportunity employer. The authors wish to acknowledge their involvement in the International Rare Disease Research Consortium. We wish to acknowledge Hugh Dawkins for his valuable feedback on this manuscript. M. Bellgard, initiated this research via a fellowship under the OECD Co-operative Research Programme: Biological Resource Management for Sustainable Agriculture Systems. This manuscript is dedicated to the memory of Professor Ernest F. Retzel (1949-2012). NR 53 TC 2 Z9 2 U1 1 U2 3 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 2211-8837 J9 HEALTH POLICY TECHN JI Health Policy Technol. PD DEC PY 2014 VL 3 IS 4 BP 325 EP 335 DI 10.1016/j.hlpt.2014.08.007 PG 11 WC Health Policy & Services SC Health Care Sciences & Services GA CK2FI UT WOS:000356025800017 ER PT J AU Liu, ZD Xu, SF Zhang, RD Li, YS Han, Y Su, CY Chen, Z Wang, H Liu, SK Zhao, QY Zhou, SJ Zhen, DZ Yu, DP Xiao, N Song, XY Qin, M AF Liu, Z. D. Xu, S. F. Zhang, R. D. Li, Y. S. Han, Y. Su, C. Y. Chen, Z. Wang, H. Liu, S. K. Zhao, Q. Y. Zhou, S. J. Zhen, D. Z. Yu, D. P. Xiao, N. Song, X. Y. Qin, M. TI CIRCULATING TUMOUR CELLS IN PERIPHERAL AND PULMONARY VENOUS BLOOD PREDICT POOR LONG-TERM SURVIVAL IN SURGICALLY RESECTED NON-SMALL CELL LUNG CANCER PATIENTS SO THORAX LA English DT Meeting Abstract CT Meeting of the British-Thoracic-Society CY DEC 03-05, 2014 CL London, ENGLAND SP British Thorac Soc C1 [Liu, Z. D.; Xu, S. F.; Li, Y. S.; Han, Y.; Su, C. Y.; Liu, S. K.; Zhao, Q. Y.; Zhou, S. J.; Zhen, D. Z.; Yu, D. P.; Xiao, N.; Song, X. Y.; Qin, M.] Capital Med Univ, Beijing Chest Hosp, Beijing, Peoples R China. [Zhang, R. D.] Capital Med Univ, Beijing Childrens Hosp, Beijing, Peoples R China. [Chen, Z.] NIDCD, Clin Genom Unit, Head & Neck Surg Branch, NIH, Bethesda, MD USA. [Wang, H.] Ludaopei Hematol Oncol Ctr, Hebei, Peoples R China. NR 0 TC 0 Z9 0 U1 0 U2 1 PU BMJ PUBLISHING GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 0040-6376 EI 1468-3296 J9 THORAX JI Thorax PD DEC PY 2014 VL 69 SU 2 MA S74 BP A41 EP A41 DI 10.1136/thoraxjnl-2014-206260.80 PG 1 WC Respiratory System SC Respiratory System GA CH2AJ UT WOS:000353825200081 ER PT J AU Laptook, AR Kilbride, H Shepherd, E McDonald, SA Shankaran, S Truog, W Das, A Higgins, RD AF Laptook, Abbot R. Kilbride, Howard Shepherd, Edward McDonald, Scott A. Shankaran, Seetha Truog, William Das, Abhik Higgins, Rosemary D. CA Optimizing Cooling Sub-Comm TI Temperature Control During Therapeutic Hypothermia for Newborn Encephalopathy Using Different Blanketrol Devices SO Therapeutic Hypothermia and Temperature Management LA English DT Article ID WHOLE-BODY HYPOTHERMIA; HYPOXIC-ISCHEMIC ENCEPHALOPATHY; SUBCUTANEOUS FAT NECROSIS; OF-THE-LITERATURE; NEONATAL ENCEPHALOPATHY; PERINATAL ASPHYXIA; SKIN; COMPLICATIONS; INFANTS; PROFILE AB Therapeutic hypothermia improves the survival and neurodevelopmental outcome of infants with newborn encephalopathy of a hypoxic-ischemic origin. The NICHD Neonatal Research Network (NRN) Whole Body Cooling trial used the Cincinnati Sub-Zero Blanketrol II to achieve therapeutic hypothermia. The Blanketrol III is now available and provides additional cooling modes that may result in better temperature control. This report is a retrospective comparison of infants undergoing hypothermia using two different cooling modes of the Blanketrol device. Infants from the NRN trial were cooled with the Blanketrol II using the Automatic control mode (B2 cohort) and were compared with infants from two new NRN centers that adopted the NRN protocol and used the Blanketrol III in a gradient mode (B3 cohort). The primary outcome was the percent time the esophageal temperature stayed between 33 degrees C and 34 degrees C (target 33.5 degrees C) during maintenance of hypothermia. Cohorts had similar birth weight, gestational age, and level of encephalopathy at the initiation of therapy. Baseline esophageal temperature differed between groups (36.6 degrees C +/- 1.0 degrees C for B2 vs. 33.9 degrees C +/- 1.2 degrees C for B3, p<0.0001) reflecting the practice of passive cooling during transport prior to initiation of active device cooling in the B3 cohort. This difference prevented comparison of temperatures during induction of hypothermia. During maintenance of hypothermia the mean and standard deviation of the percent time between 33 degrees C and 34 degrees C was similar for B2 compared to B3 cohorts (94.8%+/- 0.1% vs. 95.8%+/- 0.1%, respectively). Both the automatic and gradient control modes of the Blanketrol devices appear comparable in maintaining esophageal temperature within the target range during maintenance of therapeutic hypothermia. C1 [Laptook, Abbot R.] Brown Univ, Alpert Med Sch, Women & Infants Hosp Rhode Isl, Dept Pediat, Providence, RI 02905 USA. [Kilbride, Howard; Truog, William] Childrens Mercy Hosp, Kansas City, MO 64108 USA. [Shepherd, Edward] Nationwide Childrens Hosp, Columbus, OH USA. [McDonald, Scott A.; Das, Abhik] RTI Int, Stat & Epidemiol Unit, Res Triangle Pk, NC USA. [Shankaran, Seetha] Wayne State Univ, Detroit, MI USA. [Higgins, Rosemary D.] NICHD, Neonatal Res Network, Bethesda, MD USA. RP Laptook, AR (reprint author), Brown Univ, Alpert Med Sch, Women & Infants Hosp Rhode Isl, Dept Pediat, 101 Dudley St, Providence, RI 02905 USA. EM alaptook@wihri.org RI Shepherd, Edward/E-4080-2011 FU NICHD NIH HHS [U10 HD027904, U10 HD021385, U10 HD068284] NR 22 TC 2 Z9 2 U1 0 U2 1 PU MARY ANN LIEBERT, INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 2153-7658 EI 2153-7933 J9 THER HYPOTHERMIA TEM JI Ther. Hypothermia Temp. Manag. PD DEC 1 PY 2014 VL 4 IS 4 BP 193 EP 200 DI 10.1089/ther.2014.0009 PG 8 WC Critical Care Medicine SC General & Internal Medicine GA CG6YG UT WOS:000353448200008 PM 25285767 ER PT J AU Alexander, CJ Wagner, W Copeland, NA Jenkins, NA Hammer, JA AF Alexander, C. J. Wagner, W. Copeland, N. A. Jenkins, N. A. Hammer, J. A. TI The TAP-MYO5A mouse: a Tandem Affinity Purification tag knockin mouse for the isolation and identification of proteins that interact with myosin Va. 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 [Alexander, C. J.] NHLBI, NIH, Bethesda, MD 20892 USA. [Wagner, W.] ZMNH UKE, Hamburg, Germany. [Copeland, N. A.; Jenkins, N. A.] Methodist Hosp Res Inst, Houston, TX 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 P104 PG 1 WC Cell Biology SC Cell Biology GA CE8LP UT WOS:000352094100105 ER PT J AU Allen, AK Boateng, R Nesmith, J Golden, A AF Allen, A. K. Boateng, R. Nesmith, J. Golden, A. TI Identifying new players in meiosis using C. elegans depleted of the meiotic inhibitory kinase WEE-1.3 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 [Allen, A. K.; Boateng, R.] Howard Univ, Dept Biol, Washington, DC 20059 USA. [Nesmith, J.; 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 P2319 PG 2 WC Cell Biology SC Cell Biology GA CE8LP UT WOS:000352094105349 ER PT J AU Alushin, G Lander, G Kellogg, E Zhang, R Baker, D Nogales, E AF Alushin, G. Lander, G. Kellogg, E. Zhang, R. Baker, D. Nogales, E. TI Structural Studies into the Mechanistic Origin of Microtubule Dynamic Instability. 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 [Alushin, G.] NHLBI, Cell Biol & Physiol Ctr, Bethesda, MD 20892 USA. [Lander, G.] Scripps, Integrat Struct & Computat Biol, San Diego, CA USA. [Kellogg, E.] Univ Calif Berkeley, HHMI, Berkeley, CA USA. [Zhang, R.] LBNL, LSD, Berkeley, CA USA. [Baker, D.] Univ Washington, Seattle, WA 98195 USA. [Nogales, E.] Univ Calif Berkeley, Berkeley, CA 94720 USA. NR 0 TC 0 Z9 0 U1 3 U2 4 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 S7 PG 1 WC Cell Biology SC Cell Biology GA CE8LP UT WOS:000352094106122 ER PT J AU Bachir, A Zareno, J Moissoglu, K Plow, E Gratton, E Horwitz, AR AF Bachir, A. Zareno, J. Moissoglu, K. Plow, E. Gratton, E. Horwitz, A. R. TI Dynamic and hierarchical reorganization of integrin-associated molecular complexes in nascent 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 [Bachir, A.; Zareno, J.] Univ Virginia, Dept Cell Biol, Charlottesville, VA USA. [Moissoglu, K.] NCI, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. [Plow, E.] Cleveland Clin, Lerner Res Inst, Dept Mol Cardiol, Cleveland, OH 44106 USA. [Gratton, E.] Univ Calif Irvine, Fluorescence Dynam Lab, Irvine, CA USA. [Horwitz, A. R.] Univ Virginia, Cell Biol, Charlottesville, 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 P2223 PG 1 WC Cell Biology SC Cell Biology GA CE8LP UT WOS:000352094105253 ER PT J AU Banerjee, T Sommers, JA Huang, J Seidman, MM Brosh, RM AF Banerjee, T. Sommers, J. A. Huang, J. Seidman, M. M. Brosh, R. M. TI The conserved aromatic loop of human RECQ1 helicase is required for catalytic strand separation vital for an intact replication stress response. 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 [Banerjee, T.; Sommers, J. A.; Huang, J.; Seidman, M. M.; Brosh, R. M.] NIA, NIH, Baltimore, MD 21224 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 P1108 PG 2 WC Cell Biology SC Cell Biology GA CE8LP UT WOS:000352094102353 ER PT J AU Basrai, MA AF Basrai, M. A. 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