FN Thomson Reuters Web of Science™ VR 1.0 PT J AU Karageorgiadis, A Gourgari, E Lyssikatos, C Stratakis, CA Lodish, MB AF Karageorgiadis, Alexander Gourgari, Evgenia Lyssikatos, Charalampos Stratakis, Constantine A. Lodish, Maya Beth TI Growth Hormone and Prolactin Secretion in Patients with Carney Complex SO ENDOCRINE REVIEWS LA English DT Meeting Abstract C1 [Karageorgiadis, Alexander] NICHD, NIH, Bethesda, MD USA. [Gourgari, Evgenia] Georgetown Univ Hosp, Washington, DC 20007 USA. [Lyssikatos, Charalampos; Stratakis, Constantine A.; Lodish, Maya Beth] NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ENDOCRINE SOC PI WASHINGTON PA 2055 L ST NW, SUITE 600, WASHINGTON, DC 20036 USA SN 0163-769X EI 1945-7189 J9 ENDOCR REV JI Endocr. Rev. PD JUN PY 2014 VL 35 IS 3 SU S MA SUN-0603 PG 2 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA V45GM UT WOS:000209805100331 ER PT J AU Katz, LS Geras-Raaka, E Gershengorn, MC AF Katz, Liora S. Geras-Raaka, Elizabeth Gershengorn, Marvin C. TI Heritability of Fat Accumulation in White Adipocytes SO ENDOCRINE REVIEWS LA English DT Meeting Abstract C1 [Katz, Liora S.; Geras-Raaka, Elizabeth; Gershengorn, Marvin C.] NIDDK, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ENDOCRINE SOC PI WASHINGTON PA 2055 L ST NW, SUITE 600, WASHINGTON, DC 20036 USA SN 0163-769X EI 1945-7189 J9 ENDOCR REV JI Endocr. Rev. PD JUN PY 2014 VL 35 IS 3 SU S MA OR46-1 PG 2 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA V45GM UT WOS:000209805103190 ER PT J AU Kavarthapu, R Morris, CHT Dufau, ML AF Kavarthapu, Raghuveer Morris, Chon-Hwa Tsai Dufau, Maria L. TI Androgen Modulation of Germ Cell Nuclear Factor (GCNF) Regulates GRTH/DDX25 Specific Expression in Germ Cells SO ENDOCRINE REVIEWS LA English DT Meeting Abstract C1 [Kavarthapu, Raghuveer; Morris, Chon-Hwa Tsai] NIH, Bethesda, MD 20892 USA. [Dufau, Maria L.] NICHD, NIH, Bethesda, MD USA. NR 3 TC 0 Z9 0 U1 0 U2 0 PU ENDOCRINE SOC PI WASHINGTON PA 2055 L ST NW, SUITE 600, WASHINGTON, DC 20036 USA SN 0163-769X EI 1945-7189 J9 ENDOCR REV JI Endocr. Rev. PD JUN PY 2014 VL 35 IS 3 SU S MA PP36-4 PG 2 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA V45GM UT WOS:000209805107184 ER PT J AU Kavarthapu, R Morris, CHT Dufau, ML AF Kavarthapu, Raghuveer Morris, Chon-Hwa Tsai Dufau, Maria L. TI Androgen Modulation of Germ Cell Nuclear Factor (GCNF) Regulates GRTH/DDX25 Specific Expression in Germ Cells SO ENDOCRINE REVIEWS LA English DT Meeting Abstract C1 [Kavarthapu, Raghuveer; Morris, Chon-Hwa Tsai] NIH, Bethesda, MD 20892 USA. [Dufau, Maria L.] NICHD, NIH, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ENDOCRINE SOC PI WASHINGTON PA 2055 L ST NW, SUITE 600, WASHINGTON, DC 20036 USA SN 0163-769X EI 1945-7189 J9 ENDOCR REV JI Endocr. Rev. PD JUN PY 2014 VL 35 IS 3 SU S MA MON-0003 PG 2 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA V45GM UT WOS:000209805104155 ER PT J AU Kissell, KA Schisterman, E Hwang, BS Chen, ZS Perkins, N Wactawski-Wende, J Mumford, S AF Kissell, Kerri Ann Schisterman, Enrique Hwang, Beom Seuk Chen, Zhen Seuk Perkins, Neil Wactawski-Wende, Jean Mumford, Sunni TI History of Adverse Pregnancy Outcomes and Maternal Serum Anti-Mullerian Hormone Levels SO ENDOCRINE REVIEWS LA English DT Meeting Abstract C1 [Kissell, Kerri Ann; Schisterman, Enrique; Perkins, Neil; Mumford, Sunni] NICHD, NIH, Bethesda, MD USA. [Hwang, Beom Seuk; Chen, Zhen Seuk] NICHD, Bethesda, MD USA. [Wactawski-Wende, Jean] SUNY Buffalo, Buffalo, NY USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ENDOCRINE SOC PI WASHINGTON PA 2055 L ST NW, SUITE 600, WASHINGTON, DC 20036 USA SN 0163-769X EI 1945-7189 J9 ENDOCR REV JI Endocr. Rev. PD JUN PY 2014 VL 35 IS 3 SU S MA SUN-0015 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA V45GM UT WOS:000209805104284 ER PT J AU Latrofa, F Ricci, D Sisti, E Montanelli, L Piaggi, P Rago, T Fiore, E Marino, M Vitti, P AF Latrofa, Francesco Ricci, Debora Sisti, Eleonora Montanelli, Lucia Piaggi, Paolo Rago, Teresa Fiore, Emilio Marino, Michele Vitti, Paolo TI Evaluation of the Level of Thyroglobulin Autoantibodies Interfering with Thyroglobulin Measurement in Patients with Differentiated Thyroid Carcinoma SO ENDOCRINE REVIEWS LA English DT Meeting Abstract C1 [Latrofa, Francesco; Ricci, Debora; Sisti, Eleonora; Montanelli, Lucia; Rago, Teresa; Fiore, Emilio; Marino, Michele; Vitti, Paolo] Univ Pisa, I-56100 Pisa, Italy. [Piaggi, Paolo] NIDDK, NIH, Phoenix, AZ USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU ENDOCRINE SOC PI WASHINGTON PA 2055 L ST NW, SUITE 600, WASHINGTON, DC 20036 USA SN 0163-769X EI 1945-7189 J9 ENDOCR REV JI Endocr. Rev. PD JUN PY 2014 VL 35 IS 3 SU S MA SUN-0565 PG 2 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA V45GM UT WOS:000209805109206 ER PT J AU Latrofa, F Ricci, D Montanelli, L Piaggi, P Mazzi, B Bianchi, F Brozzi, F Santini, P Fiore, E Marino, M Tonacchera, M Vitti, P AF Latrofa, Francesco Ricci, Debora Montanelli, Lucia Piaggi, Paolo Mazzi, Barbara Bianchi, Francesca Brozzi, Federica Santini, Pierina Fiore, Emilio Marino, Michele Tonacchera, Massimo Vitti, Paolo TI Thyroglobulin Autoantibodies Switch to IgG1 and IgG3 Subclasses after 131I Treatment for Graves' Hyperthyroidism: Autoantibodies Subclasses Are Related to the Activity of Autoimmune Thyroid Disease SO ENDOCRINE REVIEWS LA English DT Meeting Abstract C1 [Latrofa, Francesco; Ricci, Debora; Montanelli, Lucia; Mazzi, Barbara; Bianchi, Francesca; Brozzi, Federica; Santini, Pierina; Fiore, Emilio; Marino, Michele; Tonacchera, Massimo; Vitti, Paolo] Univ Pisa, I-56100 Pisa, Italy. [Piaggi, Paolo] NIDDKD, NIH, Phoenix, AZ USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ENDOCRINE SOC PI WASHINGTON PA 2055 L ST NW, SUITE 600, WASHINGTON, DC 20036 USA SN 0163-769X EI 1945-7189 J9 ENDOCR REV JI Endocr. Rev. PD JUN PY 2014 VL 35 IS 3 SU S MA SAT-0538 PG 2 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA V45GM UT WOS:000209805109073 ER PT J AU Lee, P Smith, S Linderman, JD Courville, AB Brychta, RJ Dieckmann, W Werner, CD Chen, K Celi, FS AF Lee, Paul Smith, Sheila Linderman, Joyce D. Courville, Amber B. Brychta, Robert J. Dieckmann, William Werner, Charlotte D. Chen, Kong Celi, Francesco S. TI Impact of Chronic Cold Exposure in Humans (ICEMAN) Study: Evidence for Brown Adipose Tissue Plasticity Modulating Glucose Metabolism in Humans SO ENDOCRINE REVIEWS LA English DT Meeting Abstract C1 [Lee, Paul; Smith, Sheila; Linderman, Joyce D.; Brychta, Robert J.; Werner, Charlotte D.; Chen, Kong] NIDDK, Diabet Endocrinol Obes Branch, NIH, Bethesda, MD 20892 USA. [Courville, Amber B.] NIH, Ctr Clin, Bethesda, MD 20892 USA. [Dieckmann, William] NIH, PET Dept, Bethesda, MD 20892 USA. [Celi, Francesco S.] Virginia Commonwealth Univ, Richmond, VA USA. NR 3 TC 0 Z9 0 U1 0 U2 0 PU ENDOCRINE SOC PI WASHINGTON PA 2055 L ST NW, SUITE 600, WASHINGTON, DC 20036 USA SN 0163-769X EI 1945-7189 J9 ENDOCR REV JI Endocr. Rev. PD JUN PY 2014 VL 35 IS 3 SU S MA SUN-0887 PG 2 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA V45GM UT WOS:000209805103035 ER PT J AU Li, YQ Chen, M Gavrilova, O Weinstein, LS AF Li, Yong-Qi Chen, Min Gavrilova, Oksana Weinstein, Lee S. TI G(s)alpha Deficiency in Fat Tissues Leads to Improved Glucose Metabolism and Insulin Sensitivity without Effects on Body Weight SO ENDOCRINE REVIEWS LA English DT Meeting Abstract C1 [Li, Yong-Qi; Chen, Min; Gavrilova, Oksana; Weinstein, Lee S.] NIDDK, NIH, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ENDOCRINE SOC PI WASHINGTON PA 2055 L ST NW, SUITE 600, WASHINGTON, DC 20036 USA SN 0163-769X EI 1945-7189 J9 ENDOCR REV JI Endocr. Rev. PD JUN PY 2014 VL 35 IS 3 SU S MA MON-0901 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA V45GM UT WOS:000209805103042 ER PT J AU Liu, J Cinar, R Xiong, K Ntambi, JM Kunos, G AF Liu, Jie Cinar, Resat Xiong, Keming Ntambi, James M. Kunos, George TI Identification of Endogenous Inhibitors of Fatty Acid Amide Hydrolase in the Liver SO ENDOCRINE REVIEWS LA English DT Meeting Abstract C1 [Liu, Jie; Cinar, Resat] NIH, Rockville, MD USA. [Xiong, Keming; Kunos, George] NIAAA, NIH, Rockville, MD 20852 USA. [Ntambi, James M.] Univ Wisconsin, Madison, WI USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ENDOCRINE SOC PI WASHINGTON PA 2055 L ST NW, SUITE 600, WASHINGTON, DC 20036 USA SN 0163-769X EI 1945-7189 J9 ENDOCR REV JI Endocr. Rev. PD JUN PY 2014 VL 35 IS 3 SU S MA OR15-3 PG 3 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA V45GM UT WOS:000209805106049 ER PT J AU Liu, SS Emmanouil, S Mertz, E Salpea, P Shapiro, J Leikin, S Stratakis, CA AF Liu, Sisi Emmanouil, Saloustros Mertz, Edward Salpea, Paraskevi Shapiro, Jenna Leikin, Sergey Stratakis, Constantine A. TI Abnormal cAMP-Dependent Protein Kinase Activity Leads to Bone Tumors in Adult Mice but This Depends on the PKA Subunit Expressions SO ENDOCRINE REVIEWS LA English DT Meeting Abstract C1 [Liu, Sisi; Emmanouil, Saloustros; Salpea, Paraskevi; Shapiro, Jenna] NICHD, Sect Endocrinol & Genet, NIH, Bethesda, MD USA. [Mertz, Edward; Leikin, Sergey] NICHD, Sect Phys Biochem, NIH, Bethesda, MD USA. [Stratakis, Constantine A.] NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ENDOCRINE SOC PI WASHINGTON PA 2055 L ST NW, SUITE 600, WASHINGTON, DC 20036 USA SN 0163-769X EI 1945-7189 J9 ENDOCR REV JI Endocr. Rev. PD JUN PY 2014 VL 35 IS 3 SU S MA OR31-2 PG 2 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA V45GM UT WOS:000209805105212 ER PT J AU Liu, SS Berthon, AS Szarek, E Emmanouil, S Salpea, P Stratakis, CA AF Liu, Sisi Berthon, Annabel Sophie Szarek, Eva Emmanouil, Saloustros Salpea, Paraskevi Stratakis, Constantine A. TI Can COX-II Inhibitor be Used for Treatment of Cushing Syndrome Due to cAMP-Dependent Protein Kinase Defects? a Mouse Study SO ENDOCRINE REVIEWS LA English DT Meeting Abstract C1 [Liu, Sisi; Emmanouil, Saloustros; Salpea, Paraskevi] NICHD, Sect Endocrinol & Genet, NIH, Bethesda, MD USA. [Berthon, Annabel Sophie; Szarek, Eva; Stratakis, Constantine A.] NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ENDOCRINE SOC PI WASHINGTON PA 2055 L ST NW, SUITE 600, WASHINGTON, DC 20036 USA SN 0163-769X EI 1945-7189 J9 ENDOCR REV JI Endocr. Rev. PD JUN PY 2014 VL 35 IS 3 SU S MA SUN-0795 PG 3 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA V45GM UT WOS:000209805101296 ER PT J AU Liu, SS Berthon, AS Szarek, E Emmanouil, S Salpea, P Stratakis, CA AF Liu, Sisi Berthon, Annabel Sophie Szarek, Eva Emmanouil, Saloustros Salpea, Paraskevi Stratakis, Constantine A. TI Can COX-II Inhibitor be Used for Treatment of Cushing Syndrome Due to cAMP-Dependent Protein Kinase Defects? a Mouse Study SO ENDOCRINE REVIEWS LA English DT Meeting Abstract C1 [Liu, Sisi; Emmanouil, Saloustros; Salpea, Paraskevi] NICHD, Sect Endocrinol & Genet, NIH, Bethesda, MD USA. [Berthon, Annabel Sophie; Szarek, Eva; Stratakis, Constantine A.] NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ENDOCRINE SOC PI WASHINGTON PA 2055 L ST NW, SUITE 600, WASHINGTON, DC 20036 USA SN 0163-769X EI 1945-7189 J9 ENDOCR REV JI Endocr. Rev. PD JUN PY 2014 VL 35 IS 3 SU S MA PP14-2 PG 2 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA V45GM UT WOS:000209805100192 ER PT J AU Lodish, MB Ardeshirpour, Y Afshari, A Gourgari, E Keil, M Belyayskaya, E Lyssikatos, C Chernomordik, V Gandjbakhche, A Stratakis, CA AF Lodish, Maya Beth Ardeshirpour, Yasaman Afshari, Ali Gourgari, Evgenia Keil, Margaret Belyayskaya, Elena Lyssikatos, Charalampos Chernomordik, Victor Gandjbakhche, Amir Stratakis, Constantine A. TI Non-Invasive Multi-Spectral Imaging for Pre and Post-Operative Assessment of Patients with Cushing's Syndrome SO ENDOCRINE REVIEWS LA English DT Meeting Abstract C1 [Lodish, Maya Beth; Ardeshirpour, Yasaman; Afshari, Ali; Keil, Margaret; Belyayskaya, Elena; Lyssikatos, Charalampos; Stratakis, Constantine A.] NIH, Bethesda, MD 20892 USA. [Gourgari, Evgenia] Georgetown Univ Hosp, Washington, DC 20007 USA. [Chernomordik, Victor; Gandjbakhche, Amir] NICHD, Bethesda, MD USA. NR 2 TC 0 Z9 0 U1 0 U2 0 PU ENDOCRINE SOC PI WASHINGTON PA 2055 L ST NW, SUITE 600, WASHINGTON, DC 20036 USA SN 0163-769X EI 1945-7189 J9 ENDOCR REV JI Endocr. Rev. PD JUN PY 2014 VL 35 IS 3 SU S MA SAT-0830 PG 2 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA V45GM UT WOS:000209805105034 ER PT J AU London, E Nesterova, MV Huang, V Stratakis, CA AF London, Edra Nesterova, Maria V. Huang, Vincent Stratakis, Constantine A. TI Protein Kinase a (PKA) Subunit R2alpha Knockout Mice Are Leaner Than WT Mice, but Also Eat Less When Given High-Fat Diet: Is Central or Peripheral PKA Regulation the Cause of Diet-Induced Obesity (DIO) Resistance? SO ENDOCRINE REVIEWS LA English DT Meeting Abstract C1 [London, Edra] NICHD, Bethesda, MD USA. [Nesterova, Maria V.] NICHD, NIH, Bethesda, MD USA. [Huang, Vincent] NICHD, Intramural Summer Student Program NSSP, Bethesda, MD USA. [Stratakis, Constantine A.] NIH, Bethesda, MD 20892 USA. NR 3 TC 0 Z9 0 U1 0 U2 0 PU ENDOCRINE SOC PI WASHINGTON PA 2055 L ST NW, SUITE 600, WASHINGTON, DC 20036 USA SN 0163-769X EI 1945-7189 J9 ENDOCR REV JI Endocr. Rev. PD JUN PY 2014 VL 35 IS 3 SU S MA SAT-0879 PG 2 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA V45GM UT WOS:000209805103066 ER PT J AU Lui, JL Cheung, C Zhu, ZY Dimitrov, D Baron, J AF Lui, Julian Cheung, Crystal Zhu, Zhongyu Dimitrov, Dimiter Baron, Jeffrey TI Human Monoclonal Antibody Fragments for Targeting Therapeutics to Growth Plate Cartilage SO ENDOCRINE REVIEWS LA English DT Meeting Abstract C1 [Lui, Julian] NICHD, Bethesda, MD USA. [Cheung, Crystal] NIH, Bethesda, MD 20892 USA. [Zhu, Zhongyu; Dimitrov, Dimiter] NCI, Frederick, MD 21701 USA. [Baron, Jeffrey] NICHD, NIH, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ENDOCRINE SOC PI WASHINGTON PA 2055 L ST NW, SUITE 600, WASHINGTON, DC 20036 USA SN 0163-769X EI 1945-7189 J9 ENDOCR REV JI Endocr. Rev. PD JUN PY 2014 VL 35 IS 3 SU S MA OR24-4 PG 2 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA V45GM UT WOS:000209805104119 ER PT J AU Madan, R Goyal, RM Jonklaas, J Burman, K AF Madan, Ritu Goyal, Rachna Manju Jonklaas, Jacqueline Burman, Kenneth TI Methimazole Induced Fulminant Hepatic Failure SO ENDOCRINE REVIEWS LA English DT Meeting Abstract C1 [Madan, Ritu] NIH, Bethesda, MD 20892 USA. [Goyal, Rachna Manju] Georgetown Univ Hosp, Arlington, VA USA. [Jonklaas, Jacqueline] Georgetown Univ, Med Ctr, Washington, DC 20007 USA. [Burman, Kenneth] Washington Hosp Ctr, Kensington, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ENDOCRINE SOC PI WASHINGTON PA 2055 L ST NW, SUITE 600, WASHINGTON, DC 20036 USA SN 0163-769X EI 1945-7189 J9 ENDOCR REV JI Endocr. Rev. PD JUN PY 2014 VL 35 IS 3 SU S MA SAT-0468 PG 3 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA V45GM UT WOS:000209805108206 ER PT J AU Mallappa, A Daley, LA Van Ryzin, C Merke, DP AF Mallappa, Ashwini Daley, Loh-Ann Van Ryzin, Carol Merke, Deborah P. TI Quality of Life in Adults with Classic Congenital Adrenal Hyperplasia: Females Have Reduced Quality of Life Compared to Males SO ENDOCRINE REVIEWS LA English DT Meeting Abstract C1 [Mallappa, Ashwini; Daley, Loh-Ann; Van Ryzin, Carol; Merke, Deborah P.] NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 2 U2 2 PU ENDOCRINE SOC PI WASHINGTON PA 2055 L ST NW, SUITE 600, WASHINGTON, DC 20036 USA SN 0163-769X EI 1945-7189 J9 ENDOCR REV JI Endocr. Rev. PD JUN PY 2014 VL 35 IS 3 SU S MA SAT-0820 PG 2 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA V45GM UT WOS:000209805105023 ER PT J AU Mallappa, A Daley, LA Sinaii, N Van Ryzin, C Huatan, H Digweed, D Eckland, D Whitaker, M Nieman, LK Ross, RJ Merke, DP AF Mallappa, Ashwini Daley, Lori-Ann Sinaii, Ninet Van Ryzin, Carol Huatan, Hiep Digweed, Dena Eckland, David Whitaker, Martin Nieman, Lynnette K. Ross, Richard J. Merke, Deborah P. TI A Phase 2 Study of Chronocort (R), a Modified Release Formulation of Hydrocortisone, in the Treatment of Adults with Classic Congenital Adrenal Hyperplasia SO ENDOCRINE REVIEWS LA English DT Meeting Abstract C1 [Mallappa, Ashwini; Daley, Lori-Ann; Sinaii, Ninet; Van Ryzin, Carol; Nieman, Lynnette K.; Merke, Deborah P.] NIH, Bethesda, MD 20892 USA. [Huatan, Hiep; Digweed, Dena; Eckland, David; Whitaker, Martin] Diurnal Ltd, Cardiff, S Glam, Wales. [Ross, Richard J.] Univ Sheffield, Sheffield, S Yorkshire, England. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ENDOCRINE SOC PI WASHINGTON PA 2055 L ST NW, SUITE 600, WASHINGTON, DC 20036 USA SN 0163-769X EI 1945-7189 J9 ENDOCR REV JI Endocr. Rev. PD JUN PY 2014 VL 35 IS 3 SU S MA OR02-5 PG 3 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA V45GM UT WOS:000209805102326 ER PT J AU Martinez, PE Schmidt, PJ Thompson, KD Nieman, LK Morrow, AL Cintron, D Rubinow, DR AF Martinez, Pedro E. Schmidt, Peter John Thompson, Karla D. Nieman, Lynnette K. Morrow, A. Leslie Cintron, Dahima Rubinow, David R. TI Effects of Dutasteride, a 5 Alpha-Reductase Type I Inhibitor, on Pmdd Symptoms: Results of a Pilot Study SO ENDOCRINE REVIEWS LA English DT Meeting Abstract C1 [Martinez, Pedro E.] NIMH, NIH, Bethesda, MD 20892 USA. [Schmidt, Peter John; Thompson, Karla D.] NIMH, Bethesda, MD 20892 USA. [Nieman, Lynnette K.] NIH, Bethesda, MD 20892 USA. [Morrow, A. Leslie] UNC Sch Med, Chapel Hill, NC USA. [Cintron, Dahima] Univ Puerto Rico, San Juan, PR 00936 USA. [Rubinow, David R.] Univ North Carolina Chaple, Chapel Hill, NC USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ENDOCRINE SOC PI WASHINGTON PA 2055 L ST NW, SUITE 600, WASHINGTON, DC 20036 USA SN 0163-769X EI 1945-7189 J9 ENDOCR REV JI Endocr. Rev. PD JUN PY 2014 VL 35 IS 3 SU S MA SAT-0020 PG 2 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA V45GM UT WOS:000209805104251 ER PT J AU Martinez, PE Schmidt, PJ Thompson, KD Nieman, LK Morrow, AL Cintron, D Rubinow, DR AF Martinez, Pedro E. Schmidt, Peter John Thompson, Karla D. Nieman, Lynnette K. Morrow, A. Leslie Cintron, Dahima Rubinow, David R. TI Effects of Dutasteride, a 5 Alpha-Reductase Type I Inhibitor, on Pmdd Symptoms: Results of a Pilot Study SO ENDOCRINE REVIEWS LA English DT Meeting Abstract C1 [Martinez, Pedro E.] NIMH, NIH, Bethesda, MD 20892 USA. [Schmidt, Peter John; Thompson, Karla D.] NIMH, Bethesda, MD 20892 USA. [Nieman, Lynnette K.] NIH, Bethesda, MD 20892 USA. [Morrow, A. Leslie] UNC Sch Med, Chapel Hill, NC USA. [Cintron, Dahima] Univ Puerto Rico, San Juan, PR 00936 USA. [Rubinow, David R.] Univ North Carolina Chaple, Chapel Hill, NC USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ENDOCRINE SOC PI WASHINGTON PA 2055 L ST NW, SUITE 600, WASHINGTON, DC 20036 USA SN 0163-769X EI 1945-7189 J9 ENDOCR REV JI Endocr. Rev. PD JUN PY 2014 VL 35 IS 3 SU S MA PP04-3 PG 2 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA V45GM UT WOS:000209805104226 ER PT J AU Mehta, A Zhang, LS Boufraqech, M Patel, D Nilubol, N Kebebew, E AF Mehta, Amit Zhang, Lisa Boufraqech, Myriem Patel, Dhaval Nilubol, Naris Kebebew, Electron TI Carfilzomib, a Second Generation Proteasome Inhibitor, Has Anticancer Activity in Anaplastic Thyroid Cancer SO ENDOCRINE REVIEWS LA English DT Meeting Abstract C1 [Mehta, Amit; Zhang, Lisa; Boufraqech, Myriem; Patel, Dhaval; Nilubol, Naris; Kebebew, Electron] NCI, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ENDOCRINE SOC PI WASHINGTON PA 2055 L ST NW, SUITE 600, WASHINGTON, DC 20036 USA SN 0163-769X EI 1945-7189 J9 ENDOCR REV JI Endocr. Rev. PD JUN PY 2014 VL 35 IS 3 SU S MA SUN-0543 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA V45GM UT WOS:000209805109183 ER PT J AU Mehta, A Zhang, LS Boufraqech, M Patel, D Nilubol, N Davis, SR Zhang, YQ Li, ZY Shen, M Kebebew, E AF Mehta, Amit Zhang, Lisa Boufraqech, Myriem Patel, Dhaval Nilubol, Naris Davis, Sean R. Zhang, Yaqin Li, Zhuyin Shen, Min Kebebew, Electron TI Integrated Genome-Wide Expression Analysis and High Throughput Drug Screening in Anaplastic Thyroid Cancer Identifies YM155, a Survivin Inhibitor, As a Novel Therapeutic Agent SO ENDOCRINE REVIEWS LA English DT Meeting Abstract C1 [Mehta, Amit; Zhang, Lisa; Boufraqech, Myriem; Patel, Dhaval; Nilubol, Naris; Kebebew, Electron] NCI, NIH, Bethesda, MD 20892 USA. [Davis, Sean R.] NCI, Ctr Canc Res, Bethesda, MD 20892 USA. [Li, Zhuyin; Shen, Min] NIH, Natl Ctr Adv Translat Sci, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ENDOCRINE SOC PI WASHINGTON PA 2055 L ST NW, SUITE 600, WASHINGTON, DC 20036 USA SN 0163-769X EI 1945-7189 J9 ENDOCR REV JI Endocr. Rev. PD JUN PY 2014 VL 35 IS 3 SU S MA OR52-5 PG 2 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA V45GM UT WOS:000209805109146 ER PT J AU Modali, SD Desai, SS Parekh, VI Kebebew, E Agarwal, SK AF Modali, Sita D. Desai, Shruti S. Parekh, Vaishali I. Kebebew, Electron Agarwal, Sunita K. TI Tumor Suppressor Role of the Long Non-Coding RNA MEG3 in Insulinomas and in Insulinoma Cell Proliferation SO ENDOCRINE REVIEWS LA English DT Meeting Abstract C1 [Modali, Sita D.] NIDDK, NIH, Bethesda, MD USA. [Kebebew, Electron] NCI, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ENDOCRINE SOC PI WASHINGTON PA 2055 L ST NW, SUITE 600, WASHINGTON, DC 20036 USA SN 0163-769X EI 1945-7189 J9 ENDOCR REV JI Endocr. Rev. PD JUN PY 2014 VL 35 IS 3 SU S MA OR50-1 PG 3 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA V45GM UT WOS:000209805108102 ER PT J AU Morissette, R Chen, WY Xu, Z Dreilling, JL Quezado, MM McDonnell, NB Merke, DP AF Morissette, Rachel Chen, Wuyan Xu, Zhi Dreilling, Jennifer L. Quezado, Martha M. McDonnell, Nazli B. Merke, Deborah P. TI A Novel Variant in Tenascin-X May be Associated with an Ehlers Danlos Phenotype in Patients with Congenital Adrenal Hyperplasia SO ENDOCRINE REVIEWS LA English DT Meeting Abstract C1 [Morissette, Rachel; Merke, Deborah P.] NIH, Bethesda, MD 20892 USA. [Chen, Wuyan] PreventionGenet, Marshfield, WI USA. [Xu, Zhi] Univ Hong Kong, Pokfulam, Hong Kong, Peoples R China. [Dreilling, Jennifer L.; Quezado, Martha M.] NCI, Bethesda, MD 20892 USA. [McDonnell, Nazli B.] Eastern Colorado Hlth Syst, Colorado Springs, CO USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ENDOCRINE SOC PI WASHINGTON PA 2055 L ST NW, SUITE 600, WASHINGTON, DC 20036 USA SN 0163-769X EI 1945-7189 J9 ENDOCR REV JI Endocr. Rev. PD JUN PY 2014 VL 35 IS 3 SU S MA MON-0377 PG 2 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA V45GM UT WOS:000209805100291 ER PT J AU Muniyappa, R Chen, K Brychta, RJ Abel, BS Mullins, K Staker, P Van der Ploeg, LHT Connors, H Gottesdiener, K Reitman, ML Skarulis, MC AF Muniyappa, Ranganath Chen, Kong Brychta, Robert J. Abel, Brent Samuel Mullins, Katherine Staker, Pamela Van der Ploeg, Lex H. T. Connors, Hillori Gottesdiener, Keith Reitman, Marc L. Skarulis, Monica C. TI A Randomized, Double-Blind, Placebo-Controlled, Crossover Study to Evaluate the Effect of a Melanocortin Receptor 4 (MC4R) Agonist, RM-493, on Resting Energy Expenditure (REE) in Obese Subjects SO ENDOCRINE REVIEWS LA English DT Meeting Abstract C1 [Muniyappa, Ranganath; Chen, Kong; Brychta, Robert J.; Abel, Brent Samuel; Mullins, Katherine; Staker, Pamela; Reitman, Marc L.; Skarulis, Monica C.] NIH, Bethesda, MD 20892 USA. [Van der Ploeg, Lex H. T.; Connors, Hillori; Gottesdiener, Keith] Rhythm Metab Inc, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ENDOCRINE SOC PI WASHINGTON PA 2055 L ST NW, SUITE 600, WASHINGTON, DC 20036 USA SN 0163-769X EI 1945-7189 J9 ENDOCR REV JI Endocr. Rev. PD JUN PY 2014 VL 35 IS 3 SU S MA OR16-5 PG 2 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA V45GM UT WOS:000209805103140 ER PT J AU Narsana, N Madan, R Onumah, BM AF Narsana, Niyati Madan, Ritu Onumah, Barbara Mensah TI Denosumab Induced Hypocalcemia in Multiple Myeloma SO ENDOCRINE REVIEWS LA English DT Meeting Abstract C1 [Narsana, Niyati] Medstar Washington Hosp Ctr, Washington, DC USA. [Madan, Ritu] NIH, Bethesda, MD 20892 USA. [Onumah, Barbara Mensah] Washington Hosp Ctr, Washington, DC 20010 USA. NR 1 TC 0 Z9 0 U1 0 U2 0 PU ENDOCRINE SOC PI WASHINGTON PA 2055 L ST NW, SUITE 600, WASHINGTON, DC 20036 USA SN 0163-769X EI 1945-7189 J9 ENDOCR REV JI Endocr. Rev. PD JUN PY 2014 VL 35 IS 3 SU S MA SUN-0215 PG 2 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA V45GM UT WOS:000209805105146 ER PT J AU Nella, AA Mallappa, A Gounden, V Daley, LA Gonzalez, A Hindmarsh, PC Soldin, S Merke, DP AF Nella, Aikaterini A. Mallappa, Ashwini Gounden, Verena Daley, Lori-Ann Gonzalez, Adam Hindmarsh, Peter C. Soldin, Steven Merke, Deborah P. TI A Pilot Study Assessing the Use of Continuous Subcutaneous Hydrocortisone Infusion in the Treatment of Congenital Adrenal Hyperplasia: Preliminary Data SO ENDOCRINE REVIEWS LA English DT Meeting Abstract C1 [Nella, Aikaterini A.; Mallappa, Ashwini; Gounden, Verena; Daley, Lori-Ann; Gonzalez, Adam; Soldin, Steven; Merke, Deborah P.] NIH, Bethesda, MD 20892 USA. [Hindmarsh, Peter C.] UCL, London, England. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ENDOCRINE SOC PI WASHINGTON PA 2055 L ST NW, SUITE 600, WASHINGTON, DC 20036 USA SN 0163-769X EI 1945-7189 J9 ENDOCR REV JI Endocr. Rev. PD JUN PY 2014 VL 35 IS 3 SU S MA MON-0664 PG 3 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA V45GM UT WOS:000209805101287 ER PT J AU Nilsson, O Guo, M Dunbar, NS Popovic, J Flynn, DP Jacobsen, C Lui, J Hirschhorn, JN Baron, J Dauber, A AF Nilsson, Ola Guo, Michael Dunbar, Nancy S. Popovic, Jadranka Flynn, Daniel P. Jacobsen, Christina Lui, Julian Hirschhorn, Joel N. Baron, Jeffrey Dauber, Andrew TI Whole-Exome Sequencing Identifies ACAN Mutations in Autosomal Dominant Short Stature with Accelerated Skeletal Maturation SO ENDOCRINE REVIEWS LA English DT Meeting Abstract C1 [Nilsson, Ola; Baron, Jeffrey] NICHD, NIH, Bethesda, MD USA. [Guo, Michael] Harvard Med Sch, Boston, MA USA. [Dunbar, Nancy S.] Connecticut Childrens Med Ctr, Hartford, CT USA. [Popovic, Jadranka] Univ Pittsburgh, Childrens Hosp Pittsburgh, Med Ctr, Pittsburgh, PA 15213 USA. [Flynn, Daniel P.] Childrens Hosp Pittsburgh, Pittsburgh, PA 15213 USA. [Jacobsen, Christina] Chldrns Hosp Boston, Boston, MA USA. [Lui, Julian] NICHD, Bethesda, MD USA. [Hirschhorn, Joel N.; Dauber, Andrew] Boston Childrens Hosp, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ENDOCRINE SOC PI WASHINGTON PA 2055 L ST NW, SUITE 600, WASHINGTON, DC 20036 USA SN 0163-769X EI 1945-7189 J9 ENDOCR REV JI Endocr. Rev. PD JUN PY 2014 VL 35 IS 3 SU S MA OR24-1 PG 2 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA V45GM UT WOS:000209805104115 ER PT J AU Papadopoulou, A Siamatras, T Delgado-Morales, R Amin, ND Shukla, V Pant, HC Almeida, OFX Kino, T AF Papadopoulou, Anna Siamatras, Thomas Delgado-Morales, Raul Amin, Niranjana D. Shukla, Varsha Pant, Harish C. Almeida, Osborne F. X. Kino, Tomoshige TI Acute and Chronic Stress Differentially Regulate Enzymatic Activity and Protein Expression of the Cyclin-Dependent Kinase 5 (CDK5) in Mouse Brain Partly through Modulation of the Glucocorticoid Signaling Pathway: Implication to Major Depression SO ENDOCRINE REVIEWS LA English DT Meeting Abstract C1 [Papadopoulou, Anna; Siamatras, Thomas] NICHD, Program Reprod & Adult Endocrinol, NIH, Bethesda, MD USA. [Delgado-Morales, Raul; Almeida, Osborne F. X.] Max Planck Inst Psychiat, Munich, Germany. [Amin, Niranjana D.; Shukla, Varsha; Pant, Harish C.] NINDS, Bethesda, MD 20892 USA. [Kino, Tomoshige] NICHD, NIH, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU ENDOCRINE SOC PI WASHINGTON PA 2055 L ST NW, SUITE 600, WASHINGTON, DC 20036 USA SN 0163-769X EI 1945-7189 J9 ENDOCR REV JI Endocr. Rev. PD JUN PY 2014 VL 35 IS 3 SU S MA OR48-3 PG 3 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA V45GM UT WOS:000209805102039 ER PT J AU Park, JW Zhao, L Kim, DW Cheng, SY AF Park, Jeong Won Zhao, Li Kim, Dong Wook Cheng, Sheue-Yann TI Src-Dependent Phosphorylation at Tyr406 Confers the Tumor Suppressor Function of Thyroid Hormone Receptor beta SO ENDOCRINE REVIEWS LA English DT Meeting Abstract C1 [Park, Jeong Won; Zhao, Li; Kim, Dong Wook; Cheng, Sheue-Yann] NCI, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ENDOCRINE SOC PI WASHINGTON PA 2055 L ST NW, SUITE 600, WASHINGTON, DC 20036 USA SN 0163-769X EI 1945-7189 J9 ENDOCR REV JI Endocr. Rev. PD JUN PY 2014 VL 35 IS 3 SU S MA OR25-5 PG 2 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA V45GM UT WOS:000209805109128 ER PT J AU Polotsky, AJ Allshouse, AA Casson, PR Coutifaris, C Diamond, MP Christman, GM Schlaff, WD Alvero, R Trussell, JC Krawetz, SA Santoro, N Eisenberg, E Zhang, HP Legro, RS AF Polotsky, Alex Joel Allshouse, Amanda Ashleigh Casson, Peter Raymond Coutifaris, Christos Diamond, Michael P. Christman, Gregory M. Schlaff, Wlliam D. Alvero, Ruben Trussell, J. C. Krawetz, Stephen A. Santoro, Nanette Eisenberg, Esther Zhang, Heping Legro, Richard S. CA RMN TI Impact of Male Factors and Adiposity on Pregnancy and Live Birth in Pregnancy in Polycystic Ovary Syndrome II (PPCOS II) Trial SO ENDOCRINE REVIEWS LA English DT Meeting Abstract C1 [Polotsky, Alex Joel; Allshouse, Amanda Ashleigh; Alvero, Ruben; Santoro, Nanette] Univ Colorado Denver, Aurora, CO USA. [Casson, Peter Raymond] Univ Vermont, Burlington, VT USA. [Coutifaris, Christos] Hosp Univ PA, Philadelphia, PA USA. [Diamond, Michael P.] Georgia Regents Univ, Augusta, GA USA. [Christman, Gregory M.] Univ Florida, Shands Hosp, Gainesville, FL USA. [Schlaff, Wlliam D.] Jefferson Univ, Philadelphia, PA USA. [Trussell, J. C.] SUNY Upstate Med Univ, Syracuse, NY 13210 USA. [Krawetz, Stephen A.] Wayne State Univ, Sch Med, Detroit, MI USA. [Eisenberg, Esther] Vanderbilt Univ, Nashville, TN USA. [Zhang, Heping] Yale Univ, New Haven, CT USA. [Legro, Richard S.] Penn State Univ, Hershey, PA USA. [RMN] NICHD, NIH, Rockville, MD USA. NR 2 TC 0 Z9 0 U1 0 U2 0 PU ENDOCRINE SOC PI WASHINGTON PA 2055 L ST NW, SUITE 600, WASHINGTON, DC 20036 USA SN 0163-769X EI 1945-7189 J9 ENDOCR REV JI Endocr. Rev. PD JUN PY 2014 VL 35 IS 3 SU S MA SUN-0063 PG 2 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA V45GM UT WOS:000209805109078 ER PT J AU Pooley, JR Presman, DM Ganesan, S Schiltz, RL Sheshasayee, A Levi, V Keskin, O Lightman, SL Hager, GL AF Pooley, John R. Presman, Diego M. Ganesan, Sundar Schiltz, Rodney L. Sheshasayee, Ashwini Levi, Valeria Keskin, Ozlem Lightman, Stafford L. Hager, Gordon L. TI The Interaction of MR and GR in the Nucleus and at DNA: Transcriptional Implications for the Glucocorticoid Response of Stress-Associated Brain Regions SO ENDOCRINE REVIEWS LA English DT Meeting Abstract C1 [Pooley, John R.; Presman, Diego M.; Schiltz, Rodney L.; Sheshasayee, Ashwini; Hager, Gordon L.] NCI, Bethesda, MD 20892 USA. [Ganesan, Sundar] NIAID, Bethesda, MD 20892 USA. [Levi, Valeria] Univ Buenos Aires, Buenos Aires, DF, Argentina. [Keskin, Ozlem] Koc Univ, Istanbul, Turkey. [Lightman, Stafford L.] Univ Bristol, Bristol, Avon, England. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ENDOCRINE SOC PI WASHINGTON PA 2055 L ST NW, SUITE 600, WASHINGTON, DC 20036 USA SN 0163-769X EI 1945-7189 J9 ENDOCR REV JI Endocr. Rev. PD JUN PY 2014 VL 35 IS 3 SU S MA OR49-5 PG 2 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA V45GM UT WOS:000209805105040 ER PT J AU Raghavan, P Mehta, G Sharma, ST Chittiboina, P Oldfield, EH Nieman, LK AF Raghavan, Pooja Mehta, Gautam Sharma, Susmeeta T. Chittiboina, Prashant Oldfield, Edward Hudson Nieman, Lynnette K. TI Multiple Pituitary Adenomas in Cushing's Disease: A Clinical Dilemma SO ENDOCRINE REVIEWS LA English DT Meeting Abstract C1 [Raghavan, Pooja] NIH, North Bethesda, MD USA. [Mehta, Gautam; Chittiboina, Prashant; Nieman, Lynnette K.] NIH, Bethesda, MD 20892 USA. [Sharma, Susmeeta T.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, NIH, Bethesda, MD USA. [Oldfield, Edward Hudson] Univ Virginia, Charlottesville, VA USA. NR 1 TC 0 Z9 0 U1 0 U2 0 PU ENDOCRINE SOC PI WASHINGTON PA 2055 L ST NW, SUITE 600, WASHINGTON, DC 20036 USA SN 0163-769X EI 1945-7189 J9 ENDOCR REV JI Endocr. Rev. PD JUN PY 2014 VL 35 IS 3 SU S MA MON-0601 PG 3 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA V45GM UT WOS:000209805101126 ER PT J AU Raghavan, P Kassai, A Sharma, ST Peltsverger, M Nieman, LK AF Raghavan, Pooja Kassai, Andrea Sharma, Susmeeta T. Peltsverger, Maya Nieman, Lynnette K. TI Acute Psychosis As the Initial Manifestation of ACTH-Dependent Cushing's Syndrome SO ENDOCRINE REVIEWS LA English DT Meeting Abstract C1 [Raghavan, Pooja] NIH, North Bethesda, MD USA. [Kassai, Andrea; Nieman, Lynnette K.] NIH, Bethesda, MD 20892 USA. [Sharma, Susmeeta T.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, NIH, Bethesda, MD USA. [Peltsverger, Maya] New Hanover Reg Med Ctr, Wilmington, NC USA. NR 2 TC 0 Z9 0 U1 0 U2 0 PU ENDOCRINE SOC PI WASHINGTON PA 2055 L ST NW, SUITE 600, WASHINGTON, DC 20036 USA SN 0163-769X EI 1945-7189 J9 ENDOCR REV JI Endocr. Rev. PD JUN PY 2014 VL 35 IS 3 SU S MA SUN-0775 PG 3 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA V45GM UT WOS:000209805106078 ER PT J AU Raghayan, P Diker-Cohen, T Rajan, DP Sharma, ST Nieman, LK AF Raghayan, Pooja Diker-Cohen, Talia Rajan, Dhyan P. Sharma, Susmeeta T. Nieman, Lynnette K. TI Colonic Perforation As the Initial Presentation in Cushing's Disease SO ENDOCRINE REVIEWS LA English DT Meeting Abstract C1 [Raghayan, Pooja] NIH, North Bethesda, MD USA. [Diker-Cohen, Talia; Nieman, Lynnette K.] NIH, Bethesda, MD 20892 USA. [Rajan, Dhyan P.] Nassau Univ, Med Ctr, E Meadow, NY USA. [Sharma, Susmeeta T.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, NIH, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ENDOCRINE SOC PI WASHINGTON PA 2055 L ST NW, SUITE 600, WASHINGTON, DC 20036 USA SN 0163-769X EI 1945-7189 J9 ENDOCR REV JI Endocr. Rev. PD JUN PY 2014 VL 35 IS 3 SU S MA SUN-0774 PG 3 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA V45GM UT WOS:000209805106067 ER PT J AU Rago, T Scutari, M Latrofa, F Loiacono, V Piaggi, P Marchetti, I Romani, R Basolo, F Miccoli, P Tonacchera, M Vitti, P AF Rago, Teresa Scutari, Maria Latrofa, Francesco Loiacono, Valeria Piaggi, Paolo Marchetti, Ivo Romani, Rossana Basolo, Fulvio Miccoli, Paolo Tonacchera, Massimo Vitti, Paolo TI The Large Majority of 1520 Patients with Indeterminate Thyroid Nodule at Cytology Have a Favourable Outcome and a Clinical Risk Score Has a High Negative Predictive Value for a More Cumbersome Cancer Disease SO ENDOCRINE REVIEWS LA English DT Meeting Abstract C1 [Rago, Teresa; Scutari, Maria; Latrofa, Francesco; Loiacono, Valeria; Marchetti, Ivo; Romani, Rossana; Basolo, Fulvio; Miccoli, Paolo; Tonacchera, Massimo; Vitti, Paolo] Univ Pisa, Pisa, Italy. [Piaggi, Paolo] NIDDK, NIH, Phoenix, AZ USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ENDOCRINE SOC PI WASHINGTON PA 2055 L ST NW, SUITE 600, WASHINGTON, DC 20036 USA SN 0163-769X EI 1945-7189 J9 ENDOCR REV JI Endocr. Rev. PD JUN PY 2014 VL 35 IS 3 SU S MA SUN-0544 PG 2 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA V45GM UT WOS:000209805109184 ER PT J AU Ramamoorthy, S Oakley, RH Foley, JF Cidlowski, JA AF Ramamoorthy, Sivapriya Oakley, Robert H. Foley, Julie F. Cidlowski, John A. TI Glucocorticoid Receptor Isoform Knock-in Mice Have Unique Responses to Glucocorticolds SO ENDOCRINE REVIEWS LA English DT Meeting Abstract C1 [Ramamoorthy, Sivapriya; Oakley, Robert H.; Foley, Julie F.] NIEHS, Res Triangle Pk, NC 27709 USA. [Cidlowski, John A.] NIEHS, NIH, Res Triangle Pk, NC 27709 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ENDOCRINE SOC PI WASHINGTON PA 2055 L ST NW, SUITE 600, WASHINGTON, DC 20036 USA SN 0163-769X EI 1945-7189 J9 ENDOCR REV JI Endocr. Rev. PD JUN PY 2014 VL 35 IS 3 SU S MA OR49-4 PG 2 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA V45GM UT WOS:000209805105039 ER PT J AU Ramirez, AH Niven, RA Wood, BJ Chang, R Marx, SJ Collins, MT AF Ramirez, Andrea Havens Niven, Ruth A. Wood, Bradford J. Chang, Richard Marx, Stephen J. Collins, Michael T. TI Successful Palliation of Metastatic Parathyroid Carcinoma with Denosumab and Microwave and Radiofrequency Ablation SO ENDOCRINE REVIEWS LA English DT Meeting Abstract C1 [Ramirez, Andrea Havens; Wood, Bradford J.] NIH, Bethesda, MD 20892 USA. [Niven, Ruth A.] Tel Aviv Univ, Tel Aviv, Israel. [Chang, Richard] NIH, Radiol & Imaging Sci, Bethesda, MD 20892 USA. [Marx, Stephen J.] NIDDK, NIH, Bethesda, MD 20892 USA. [Collins, Michael T.] NIDCD, NIH, Bethesda, MD USA. NR 2 TC 0 Z9 0 U1 0 U2 0 PU ENDOCRINE SOC PI WASHINGTON PA 2055 L ST NW, SUITE 600, WASHINGTON, DC 20036 USA SN 0163-769X EI 1945-7189 J9 ENDOCR REV JI Endocr. Rev. PD JUN PY 2014 VL 35 IS 3 SU S MA SAT-0295 PG 3 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA V45GM UT WOS:000209805108023 ER PT J AU Ramnitz, MS Del Rivero, J Gourh, P Ovejero, D Bhattacharyya, N Guthrie, L Goldbach-Mansky, R Wodajo, F Seo-Mayer, P Arabshahi, B Jackson, M Boskey, A White, KE Molinolo, AA Gafni, RI Collins, MT AF Ramnitz, Mary Scott Del Rivero, Jaydira Gourh, Pravitt Ovejero, Diana Bhattacharyya, Nisan Guthrie, Lori Goldbach-Mansky, Raphaela Wodajo, Felasfa Seo-Mayer, Patricia Arabshahi, Bita Jackson, Malaka Boskey, Adele White, Kenneth E. Molinolo, Alfredo A. Gafni, Rachel I. Collins, Michael T. TI Familial Tumoral Calcinosis: Lessons from a Rare Disorder of Ectopic Mineralization SO ENDOCRINE REVIEWS LA English DT Meeting Abstract C1 [Ramnitz, Mary Scott; Gourh, Pravitt; Ovejero, Diana; Bhattacharyya, Nisan; Guthrie, Lori; Goldbach-Mansky, Raphaela; Molinolo, Alfredo A.; Gafni, Rachel I.; Collins, Michael T.] NIH, Bethesda, MD 20892 USA. [Del Rivero, Jaydira] NICHHD, NIH, Bethesda, MD 20892 USA. [Wodajo, Felasfa] Virginia Hosp Ctr, Arlington, VA USA. [Seo-Mayer, Patricia] Pediat Specialists Virginia, Fairfax, VA USA. [Arabshahi, Bita] Inova Fairfax Hosp, Falls Church, VA USA. [Jackson, Malaka] Univ South Carolina, Sch Med, Columbia, SC USA. [Boskey, Adele] Cornell Univ, Weill Med Coll, Ithaca, NY 14853 USA. [White, Kenneth E.] Indiana Univ Sch Med, Indianapolis, IN 46202 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ENDOCRINE SOC PI WASHINGTON PA 2055 L ST NW, SUITE 600, WASHINGTON, DC 20036 USA SN 0163-769X EI 1945-7189 J9 ENDOCR REV JI Endocr. Rev. PD JUN PY 2014 VL 35 IS 3 SU S MA SAT-0222 PG 2 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA V45GM UT WOS:000209805105178 ER PT J AU Reitman, ML Lute, B Jou, W Lateef, D Goldgof, M Xiao, CY Pinol, RA Kravitz, A Huang, YG Girardet, C Butler, A Gavrilova, O AF Reitman, Marc L. Lute, Beth Jou, William Lateef, Dalya Goldgof, Margalit Xiao, Cuiying Pinol, Ramon A. Kravitz, Alexxai Huang, Yuning George Girardet, Clemence Butler, Andrew Gavrilova, Oksana TI Biphasic Effect of Melanocortin Agonist Mtii on Metabolic Rate and Body Temperature SO ENDOCRINE REVIEWS LA English DT Meeting Abstract C1 [Reitman, Marc L.] Diabet Endocrinol & Obes Branch, Bethesda, MD USA. [Lute, Beth; Jou, William; Lateef, Dalya; Goldgof, Margalit; Xiao, Cuiying; Pinol, Ramon A.; Kravitz, Alexxai; Huang, Yuning George; Gavrilova, Oksana] NIDDK, NIH, Bethesda, MD USA. [Girardet, Clemence] Scripps Res Inst, Jupiter, FL USA. [Butler, Andrew] St Louis Univ, Sch Med, St Louis, MO USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ENDOCRINE SOC PI WASHINGTON PA 2055 L ST NW, SUITE 600, WASHINGTON, DC 20036 USA SN 0163-769X EI 1945-7189 J9 ENDOCR REV JI Endocr. Rev. PD JUN PY 2014 VL 35 IS 3 SU S MA OR16-4 PG 2 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA V45GM UT WOS:000209805103138 ER PT J AU Reyes-Capo, DP Marshal, JD Naggert, JK Bryant, JC Hicks, MD Kattapurami, MM Heller, T Liu, CY Turkbey, E Myles, JG Bernstein, SB Reynolds, JC Shamburek, RD Gahl, WA Gunay-Aygun, M Han, JC AF Reyes-Capo, Daniela P. Marshal, Jan D. Naggert, Jurgen K. Bryant, Joy C. Hicks, Melanie D. Kattapurami, Meera M. Heller, Theo Liu, Chia-Ying Turkbey, Evrim Myles, Jennifer G. Bernstein, Shanna B. Reynolds, James C. Shamburek, Robert D. Gahl, William A. Gunay-Aygun, Meral Han, Joan C. TI Endocrine and Metabolic Characterization of Alstrom Syndrome SO ENDOCRINE REVIEWS LA English DT Meeting Abstract C1 [Reyes-Capo, Daniela P.; Bryant, Joy C.; Hicks, Melanie D.; Kattapurami, Meera M.; Heller, Theo; Liu, Chia-Ying; Turkbey, Evrim; Myles, Jennifer G.; Bernstein, Shanna B.; Reynolds, James C.; Shamburek, Robert D.; Gahl, William A.; Gunay-Aygun, Meral; Han, Joan C.] NIH, Bethesda, MD 20892 USA. [Marshal, Jan D.; Naggert, Jurgen K.] Jackson Lab, Bar Harbor, ME 04609 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ENDOCRINE SOC PI WASHINGTON PA 2055 L ST NW, SUITE 600, WASHINGTON, DC 20036 USA SN 0163-769X EI 1945-7189 J9 ENDOCR REV JI Endocr. Rev. PD JUN PY 2014 VL 35 IS 3 SU S MA MON-0929 PG 2 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA V45GM UT WOS:000209805103255 ER PT J AU Roth, MY Shih, G Ilani, N Wang, C Page, ST Bremner, WJ Swerdloff, RS Sitruk-Ware, R Blithe, DL Amory, JK AF Roth, Mara Yvonne Shih, Grace Ilani, Niloufar Wang, Christina Page, Stephanie T. Bremner, William J. Swerdloff, Ronald S. Sitruk-Ware, Regine Blithe, Diana Lynn Amory, John K. TI High Acceptability of a Combination of Nestorone (R) and Testosterone Gels for Male Hormonal Contraception in a Randomized Controlled Trial SO ENDOCRINE REVIEWS LA English DT Meeting Abstract C1 [Roth, Mara Yvonne; Shih, Grace; Page, Stephanie T.; Bremner, William J.; Amory, John K.] Univ Washington, Seattle, WA 98195 USA. [Ilani, Niloufar; Wang, Christina] Harbor UCLA Med Ctr, Torrance, CA 90509 USA. [Ilani, Niloufar; Wang, Christina; Swerdloff, Ronald S.] Los Angeles Biomed Res Inst, Torrance, CA USA. [Page, Stephanie T.] Harborview Med Ctr, Seattle, WA USA. [Swerdloff, Ronald S.] Harbor Univ Calif, Med Ctr, Torrance, CA USA. [Sitruk-Ware, Regine] Populat Council, New York, NY 10021 USA. [Blithe, Diana Lynn] NICHHD, Bethesda, MD 20892 USA. NR 3 TC 0 Z9 0 U1 0 U2 0 PU ENDOCRINE SOC PI WASHINGTON PA 2055 L ST NW, SUITE 600, WASHINGTON, DC 20036 USA SN 0163-769X EI 1945-7189 J9 ENDOCR REV JI Endocr. Rev. PD JUN PY 2014 VL 35 IS 3 SU S MA SUN-0061 PG 2 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA V45GM UT WOS:000209805109055 ER PT J AU Sadowski, SM Millo, CM Cottle-Delisie, C Merkel, R Yang, L Marx, SJ Nilubol, N Herscovitch, P Kebebew, E AF Sadowski, Samira Mercedes Millo, Corina M. Cottle-Delisie, Candice Merkel, Roxanne Yang, Lily Marx, Stephen J. Nilubol, Naris Herscovitch, Peter Kebebew, Electron TI Prospective Evaluation of 68Gallium-Dotatate PET/CT in Detecting Unknown Primary and Metastatic Neuroendocrine Tumors SO ENDOCRINE REVIEWS LA English DT Meeting Abstract C1 [Sadowski, Samira Mercedes; Cottle-Delisie, Candice; Merkel, Roxanne; Yang, Lily; Nilubol, Naris; Kebebew, Electron] NCI, NIH, Bethesda, MD 20892 USA. [Millo, Corina M.; Herscovitch, Peter] NIH, Ctr Clin, Bethesda, MD 20892 USA. [Marx, Stephen J.] NIDDK, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ENDOCRINE SOC PI WASHINGTON PA 2055 L ST NW, SUITE 600, WASHINGTON, DC 20036 USA SN 0163-769X EI 1945-7189 J9 ENDOCR REV JI Endocr. Rev. PD JUN PY 2014 VL 35 IS 3 SU S MA SAT-0302 PG 3 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA V45GM UT WOS:000209805108063 ER PT J AU Schernthaner-Reiter, MH Trivellin, G Nesterova, MV Hernandez-Ramirez, LC Aflorei, ED Sierra, MD Stratakis, CA Korbonits, M AF Schernthaner-Reiter, Marie Helene Trivellin, Giampaolo Nesterova, Maria V. Hernandez-Ramirez, Laura C. Aflorei, Elena Daniela Sierra, Maria De La Luz Stratakis, Constantine A. Korbonits, Marta TI Interaction of AIP with the cAMP-Dependent Protein Kinase (PKA) Pathway and Its Role in Pituitary Tumor Formation SO ENDOCRINE REVIEWS LA English DT Meeting Abstract C1 [Schernthaner-Reiter, Marie Helene; Trivellin, Giampaolo; Nesterova, Maria V.; Sierra, Maria De La Luz; Stratakis, Constantine A.] NIH, Bethesda, MD 20892 USA. [Hernandez-Ramirez, Laura C.; Aflorei, Elena Daniela; Korbonits, Marta] Queen Mary Univ London, Barts & London Sch Med, William Harvey Res Inst, London, England. NR 2 TC 0 Z9 0 U1 0 U2 0 PU ENDOCRINE SOC PI WASHINGTON PA 2055 L ST NW, SUITE 600, WASHINGTON, DC 20036 USA SN 0163-769X EI 1945-7189 J9 ENDOCR REV JI Endocr. Rev. PD JUN PY 2014 VL 35 IS 3 SU S MA SAT-0640 PG 2 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA V45GM UT WOS:000209805109322 ER PT J AU Schernthaner-Reiter, MH Trivellin, G Nesterova, MV Hernandez-Ramirez, LC Aflorei, ED Sierra, MD Stratakis, CA Korbonits, M AF Schernthaner-Reiter, Marie Helene Trivellin, Giampaolo Nesterova, Maria V. Hernandez-Ramirez, Laura C. Aflorei, Elena Daniela Sierra, Maria De La Luz Stratakis, Constantine A. Korbonits, Marta TI Interaction of AIP with the cAMP-Dependent Protein Kinase (PKA) Pathway and Its Role in Pituitary Tumor Formation SO ENDOCRINE REVIEWS LA English DT Meeting Abstract C1 [Schernthaner-Reiter, Marie Helene; Trivellin, Giampaolo; Nesterova, Maria V.; Sierra, Maria De La Luz; Stratakis, Constantine A.] NIH, Bethesda, MD 20892 USA. [Hernandez-Ramirez, Laura C.; Aflorei, Elena Daniela; Korbonits, Marta] Queen Mary Univ London, Barts & London Sch Med, William Harvey Res Inst, London, England. NR 2 TC 0 Z9 0 U1 0 U2 0 PU ENDOCRINE SOC PI WASHINGTON PA 2055 L ST NW, SUITE 600, WASHINGTON, DC 20036 USA SN 0163-769X EI 1945-7189 J9 ENDOCR REV JI Endocr. Rev. PD JUN PY 2014 VL 35 IS 3 SU S MA PP09-4 PG 3 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA V45GM UT WOS:000209805102106 ER PT J AU Schlogl, M Votruba, S Piaggi, P Walter, M Krakoff, J Thearle, MS AF Schlogl, Mathias Votruba, Susi Piaggi, Paolo Walter, Mary Krakoff, Jonathan Thearle, Marie S. TI Higher 24h Ad Libitum Food Intake Predicts Lower Fasting Plasma Irisin Concentrations in Adult Humans SO ENDOCRINE REVIEWS LA English DT Meeting Abstract C1 [Schlogl, Mathias] NIDDK, Phoenix Epidemiol & Clin Res Branch, NIH, Phoenix, AZ USA. [Votruba, Susi; Piaggi, Paolo; Thearle, Marie S.] NIDDK, NIH, Phoenix, AZ USA. [Walter, Mary] NIDDK, NIH, Bethesda, MD 20892 USA. [Krakoff, Jonathan] NIDDK, Phoenix Epidemiol & Clin Res Branch, NIH, Phoenix, AZ USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ENDOCRINE SOC PI WASHINGTON PA 2055 L ST NW, SUITE 600, WASHINGTON, DC 20036 USA SN 0163-769X EI 1945-7189 J9 ENDOCR REV JI Endocr. Rev. PD JUN PY 2014 VL 35 IS 3 SU S MA SUN-0875 PG 2 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA V45GM UT WOS:000209805103023 ER PT J AU Sertedaki, A Markou, A Kaltsas, GA Androulakis, L Pappa, T Gouli, A Papanastasiou, L Zacharoulis, A Karavidas, A Ragkou, D Vlachakis, D Kossida, S Campanac, E Hoffman, DA De La Luz, M Xekouki, P Stratakis, CA Charmandari, E Chrousos, GP Piaditis, GP AF Sertedaki, Amalia Markou, Athina Kaltsas, Gregory A. Androulakis, Loannis Pappa, Theodora Gouli, Aggeliki Papanastasiou, Labrini Zacharoulis, Achilles Karavidas, Apostolos Ragkou, Despoina Vlachakis, Dimitrios Kossida, Sophia Campanac, Emilie Hoffman, Dax A. De La Luz, Maria Xekouki, Paraskevi Stratakis, Constantine A. Charmandari, Evangelia Chrousos, George P. Piaditis, Georgios P. TI Mutations of the KCNJ5 Gene in Patients with Hypertension and Increased Aldosterone Response to ACTH SO ENDOCRINE REVIEWS LA English DT Meeting Abstract C1 [Sertedaki, Amalia; Kaltsas, Gregory A.; Charmandari, Evangelia; Chrousos, George P.] Univ Athens, Sch Med, Athens, Greece. [Markou, Athina; Androulakis, Loannis; Pappa, Theodora; Gouli, Aggeliki; Papanastasiou, Labrini; Zacharoulis, Achilles; Karavidas, Apostolos; Ragkou, Despoina; Piaditis, Georgios P.] G Gennimatas Gen Hosp, Athens, Greece. [Vlachakis, Dimitrios; Kossida, Sophia] Acad Athens, Biomed Res Fdn, Athens, Greece. [Campanac, Emilie; Hoffman, Dax A.; De La Luz, Maria; Xekouki, Paraskevi; Stratakis, Constantine A.] NIH, Bethesda, MD 20892 USA. RI Charmandari, Evangelia/B-6701-2011 NR 0 TC 0 Z9 0 U1 0 U2 0 PU ENDOCRINE SOC PI WASHINGTON PA 2055 L ST NW, SUITE 600, WASHINGTON, DC 20036 USA SN 0163-769X EI 1945-7189 J9 ENDOCR REV JI Endocr. Rev. PD JUN PY 2014 VL 35 IS 3 SU S MA SAT-0837 PG 3 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA V45GM UT WOS:000209805106105 ER PT J AU Sertedaki, A Markou, A Kaltsas, GA Androulakis, L Pappa, T Gouli, A Papanastasiou, L Zacharoulis, A Karavidas, A Ragkou, D Vlachakis, D Kossida, S Campanac, E Hoffman, DA De La Luz, M Xekouki, P Stratakis, CA Charmandari, E Chrousos, GP Piaditis, GP AF Sertedaki, Amalia Markou, Athina Kaltsas, Gregory A. Androulakis, Loannis Pappa, Theodora Gouli, Aggeliki Papanastasiou, Labrini Zacharoulis, Achilles Karavidas, Apostolos Ragkou, Despoina Vlachakis, Dimitrios Kossida, Sophia Campanac, Emilie Hoffman, Dax A. De La Luz, Maria Xekouki, Paraskevi Stratakis, Constantine A. Charmandari, Evangelia Chrousos, George P. Piaditis, Georgios P. TI Mutations of the KCNJ5 Gene in Patients with Hypertension and Increased Aldosterone Response to ACTH SO ENDOCRINE REVIEWS LA English DT Meeting Abstract C1 [Sertedaki, Amalia; Kaltsas, Gregory A.; Charmandari, Evangelia; Chrousos, George P.] Univ Athens, Sch Med, Athens, Greece. [Markou, Athina; Androulakis, Loannis; Pappa, Theodora; Gouli, Aggeliki; Papanastasiou, Labrini; Zacharoulis, Achilles; Karavidas, Apostolos; Ragkou, Despoina; Piaditis, Georgios P.] G Gennimatas Gen Hosp, Athens, Greece. [Vlachakis, Dimitrios; Kossida, Sophia] Acad Athens, Biomed Res Fdn, Athens, Greece. [Campanac, Emilie; Hoffman, Dax A.; De La Luz, Maria; Xekouki, Paraskevi; Stratakis, Constantine A.] NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ENDOCRINE SOC PI WASHINGTON PA 2055 L ST NW, SUITE 600, WASHINGTON, DC 20036 USA SN 0163-769X EI 1945-7189 J9 ENDOCR REV JI Endocr. Rev. PD JUN PY 2014 VL 35 IS 3 SU S MA PP06-4 PG 3 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA V45GM UT WOS:000209805106082 ER PT J AU Sfeir, JG Rother, KI Popii, VB AF Sfeir, Jad G. Rother, Kristina I. Popii, Violeta Botea TI Liraglutide: An Alternative to Insulin for New Onset Type 1 Diabetes in Adults? SO ENDOCRINE REVIEWS LA English DT Meeting Abstract C1 [Sfeir, Jad G.] Lankenau Med Ctr, Wynnewood, PA USA. [Rother, Kristina I.] NIDDK, Bethesda, MD 20892 USA. [Popii, Violeta Botea] Main Line Hlth, Wynnewood, PA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ENDOCRINE SOC PI WASHINGTON PA 2055 L ST NW, SUITE 600, WASHINGTON, DC 20036 USA SN 0163-769X EI 1945-7189 J9 ENDOCR REV JI Endocr. Rev. PD JUN PY 2014 VL 35 IS 3 SU S MA SUN-0977 PG 2 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA V45GM UT WOS:000209805107046 ER PT J AU Shapiro, J Liu, S Stratakis, CA AF Shapiro, Jenna Liu, Sisi Stratakis, Constantine A. TI Alteration of PKA Subunit Expression on the Osteogenic Behavior of MC3T3 Murine Pre-Osteoblasts SO ENDOCRINE REVIEWS LA English DT Meeting Abstract C1 [Shapiro, Jenna; Liu, Sisi] NICHD, Sect Endocrinol & Genet, NIH, Bethesda, MD USA. [Stratakis, Constantine A.] NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ENDOCRINE SOC PI WASHINGTON PA 2055 L ST NW, SUITE 600, WASHINGTON, DC 20036 USA SN 0163-769X EI 1945-7189 J9 ENDOCR REV JI Endocr. Rev. PD JUN PY 2014 VL 35 IS 3 SU S MA MON-0234 PG 2 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA V45GM UT WOS:000209805105205 ER PT J AU Sharma, ST Yanovski, JA Abraham, SB Nieman, LK AF Sharma, Susmeeta T. Yanovski, Jack A. Abraham, Smita Baid Nieman, Lynnette K. TI Utility of Measurement of Dexamethasone Levels in the Diagnostic Testing for Cushing's Syndrome SO ENDOCRINE REVIEWS LA English DT Meeting Abstract C1 [Sharma, Susmeeta T.; Abraham, Smita Baid] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, NIH, Bethesda, MD USA. [Yanovski, Jack A.; Nieman, Lynnette K.] NIH, Bethesda, MD 20892 USA. NR 4 TC 0 Z9 0 U1 0 U2 0 PU ENDOCRINE SOC PI WASHINGTON PA 2055 L ST NW, SUITE 600, WASHINGTON, DC 20036 USA SN 0163-769X EI 1945-7189 J9 ENDOCR REV JI Endocr. Rev. PD JUN PY 2014 VL 35 IS 3 SU S MA OR02-1 PG 3 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA V45GM UT WOS:000209805102281 ER PT J AU Sharma, ST Sinaii, N Nieman, LK AF Sharma, Susmeeta T. Sinaii, Ninet Nieman, Lynnette K. TI Factors Predicting the Development of Severe Transanninitis with Ketoconazole Treatment in Cushing's Syndrome SO ENDOCRINE REVIEWS LA English DT Meeting Abstract C1 [Sharma, Susmeeta T.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, NIH, Bethesda, MD USA. [Sinaii, Ninet; Nieman, Lynnette K.] NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ENDOCRINE SOC PI WASHINGTON PA 2055 L ST NW, SUITE 600, WASHINGTON, DC 20036 USA SN 0163-769X EI 1945-7189 J9 ENDOCR REV JI Endocr. Rev. PD JUN PY 2014 VL 35 IS 3 SU S MA PP27-1 PG 2 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA V45GM UT WOS:000209805100137 ER PT J AU Sharma, ST Sinaii, N Nieman, LK AF Sharma, Susmeeta T. Sinaii, Ninet Nieman, Lynnette K. TI Factors Predicting the Development of Severe Transanninitis with Ketoconazole Treatment in Cushing's Syndrome SO ENDOCRINE REVIEWS LA English DT Meeting Abstract C1 [Sharma, Susmeeta T.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, NIH, Bethesda, MD USA. [Sinaii, Ninet; Nieman, Lynnette K.] NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ENDOCRINE SOC PI WASHINGTON PA 2055 L ST NW, SUITE 600, WASHINGTON, DC 20036 USA SN 0163-769X EI 1945-7189 J9 ENDOCR REV JI Endocr. Rev. PD JUN PY 2014 VL 35 IS 3 SU S MA MON-0772 PG 2 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA V45GM UT WOS:000209805103071 ER PT J AU Sharma, ST Sinaii, N Nieman, LK AF Sharma, Susmeeta T. Sinaii, Ninet Nieman, Lynnette K. TI Combination Treatment with Ketoconazole and Metyrapone in Cushing's Syndrome SO ENDOCRINE REVIEWS LA English DT Meeting Abstract C1 [Sharma, Susmeeta T.] Eunice Kennedy Shrivel Natl Inst Child Hlth & Hum, NIH, Bethesda, MD USA. [Sinaii, Ninet; Nieman, Lynnette K.] NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ENDOCRINE SOC PI WASHINGTON PA 2055 L ST NW, SUITE 600, WASHINGTON, DC 20036 USA SN 0163-769X EI 1945-7189 J9 ENDOCR REV JI Endocr. Rev. PD JUN PY 2014 VL 35 IS 3 SU S MA MON-0777 PG 2 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA V45GM UT WOS:000209805103128 ER PT J AU Shulman, DI Winer, KK AF Shulman, Dorothy I. Winer, Karen K. TI Results of One Year of Therapy with Recombinant Human Parathyroid Hormone 1-34 (rhPTH 1-34) Delivered By Insulin Pump in 3 Women with Activating Mutations of the Calcium Sensing Receptor (CASR) SO ENDOCRINE REVIEWS LA English DT Meeting Abstract C1 [Shulman, Dorothy I.] Univ S FL, Morsani Coll Med, Tampa, FL USA. [Winer, Karen K.] NIH, Bldg 10, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ENDOCRINE SOC PI WASHINGTON PA 2055 L ST NW, SUITE 600, WASHINGTON, DC 20036 USA SN 0163-769X EI 1945-7189 J9 ENDOCR REV JI Endocr. Rev. PD JUN PY 2014 VL 35 IS 3 SU S MA MON-0193 PG 2 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA V45GM UT WOS:000209805105055 ER PT J AU Slominski, A Kim, TK Takeda, Y Janjetovic, Z Brozyna, A Skobowiat, C Wang, J Postlethwaite, A Li, W Tuckey, RC Jetten, AM AF Slominski, Andrzej Kim, Tae-Kang Takeda, Yukimasa Janjetovic, Zorica Brozyna, Anna Skobowiat, Cezary Wang, Jin Postlethwaite, Arnold Li, Wei Tuckey, Robert C. Jetten, Anton M. TI RORa and RORg Are Expressed in Human Skin and Serve As Receptors for Endogenously Produced Noncalcemic 20-Hydroxy- and 20,23-Dihydroxy-Vitamin D SO ENDOCRINE REVIEWS LA English DT Meeting Abstract C1 [Slominski, Andrzej; Kim, Tae-Kang; Janjetovic, Zorica; Skobowiat, Cezary; Wang, Jin; Postlethwaite, Arnold; Li, Wei] Univ Tennessee, HSC, Memphis, TN USA. [Takeda, Yukimasa; Jetten, Anton M.] NIEHS, NIH, Res Triangle Pk, NC 27709 USA. [Brozyna, Anna] Nicolaus Copernicus Univ, Torun, Poland. [Tuckey, Robert C.] Univ Western Australia, Crawley, Australia. NR 4 TC 0 Z9 0 U1 0 U2 0 PU ENDOCRINE SOC PI WASHINGTON PA 2055 L ST NW, SUITE 600, WASHINGTON, DC 20036 USA SN 0163-769X EI 1945-7189 J9 ENDOCR REV JI Endocr. Rev. PD JUN PY 2014 VL 35 IS 3 SU S MA SAT-0407 PG 3 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA V45GM UT WOS:000209805102288 ER PT J AU Sumner, AE Thoreson, CK O'Connor, MY Reynolds, JC Ricks, M Chung, ST AF Sumner, Anne E. Thoreson, Caroline K. O'Connor, Michelle Y. Reynolds, James C. Ricks, Madia Chung, Stephanie T. TI Vitamin D Levels Defined As Insufficient By the Institute of Medicine and the Endocrine Society May be Adequate in Africans SO ENDOCRINE REVIEWS LA English DT Meeting Abstract C1 [Sumner, Anne E.; Thoreson, Caroline K.; O'Connor, Michelle Y.; Ricks, Madia; Chung, Stephanie T.] NIDDK, NIH, Bethesda, MD 20892 USA. [Reynolds, James C.] NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ENDOCRINE SOC PI WASHINGTON PA 2055 L ST NW, SUITE 600, WASHINGTON, DC 20036 USA SN 0163-769X EI 1945-7189 J9 ENDOCR REV JI Endocr. Rev. PD JUN PY 2014 VL 35 IS 3 SU S MA SAT-0248 PG 2 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA V45GM UT WOS:000209805105319 ER PT J AU Suzuki, S Kino, T AF Suzuki, Shigeru Kino, Tomoshige TI Sirt1 Enhances the Transcriptional Activity of the Glucocorticoid Receptor in Its Deacetylase Activity-Independent Fashion SO ENDOCRINE REVIEWS LA English DT Meeting Abstract C1 [Suzuki, Shigeru; Kino, Tomoshige] NICHD, NIH, Bethesda, MD USA. NR 1 TC 0 Z9 0 U1 0 U2 0 PU ENDOCRINE SOC PI WASHINGTON PA 2055 L ST NW, SUITE 600, WASHINGTON, DC 20036 USA SN 0163-769X EI 1945-7189 J9 ENDOCR REV JI Endocr. Rev. PD JUN PY 2014 VL 35 IS 3 SU S MA SUN-0433 PG 3 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA V45GM UT WOS:000209805102229 ER PT J AU Swerdloff, RS Pak, Y Wang, C Liu, PY Bhasin, S Gill, TM Matsumoto, AM Pahor, M Surampudi, P Romashkan, S Hadley, E Snyder, PJ AF Swerdloff, Ronald S. Pak, Youngju Wang, Christina Liu, Peter Y. Bhasin, Shalender Gill, Thomas M. Matsumoto, Alvin M. Pahor, Marco Surampudi, Prasanth Romashkan, Sergei Hadley, Evan Snyder, Peter J. TI Testosterone Pharmacokinetics (PK) in Older Men Participating in the Testosterone Trials (The T Trials) SO ENDOCRINE REVIEWS LA English DT Meeting Abstract C1 [Swerdloff, Ronald S.; Pak, Youngju; Wang, Christina; Surampudi, Prasanth] Harbor UCLA Med Ctr, Torrance, CA 90509 USA. [Swerdloff, Ronald S.; Pak, Youngju; Wang, Christina; Surampudi, Prasanth] Los Angeles Biomed Res Inst, Torrance, CA USA. [Liu, Peter Y.] Harbor UCLA Med Ctr, Los Angeles, CA USA. [Liu, Peter Y.] Los Angeles Biomed Res Inst, Los Angeles, CA USA. [Bhasin, Shalender] Harvard Med Sch, Brigham & Womens Hosp, Boston, MA USA. [Gill, Thomas M.] Yale Sch Med, New Haven, CT USA. [Matsumoto, Alvin M.] VA Puget Sound Hlth Care Sys, Seattle, WA USA. [Pahor, Marco] Univ Florida, Gainesville, FL USA. [Romashkan, Sergei; Hadley, Evan] NIA, Bethesda, MD 20892 USA. [Snyder, Peter J.] Univ Penn, Philadelphia, PA 19104 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ENDOCRINE SOC PI WASHINGTON PA 2055 L ST NW, SUITE 600, WASHINGTON, DC 20036 USA SN 0163-769X EI 1945-7189 J9 ENDOCR REV JI Endocr. Rev. PD JUN PY 2014 VL 35 IS 3 SU S MA SUN-0086 PG 2 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA V45GM UT WOS:000209805107202 ER PT J AU Szarek, E Leal, LF Kotula-Balak, M Bilinska, B Stratakis, CA AF Szarek, Eva Leal, Leticia Ferro Kotula-Balak, Malgorzata Bilinska, Barbara Stratakis, Constantine A. TI A cAMP-Specific Phosphodiesterase, Phosphodiesterase 8B (PDE8B), Affects Sertoli Cell Proliferation in Adult Mice SO ENDOCRINE REVIEWS LA English DT Meeting Abstract C1 [Szarek, Eva; Stratakis, Constantine A.] NIH, Bethesda, MD 20892 USA. [Leal, Leticia Ferro] Univ Sao Paulo, Ribeirao Preto, SP, Brazil. [Kotula-Balak, Malgorzata; Bilinska, Barbara] Jagiellonian Univ, Krakow, Poland. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ENDOCRINE SOC PI WASHINGTON PA 2055 L ST NW, SUITE 600, WASHINGTON, DC 20036 USA SN 0163-769X EI 1945-7189 J9 ENDOCR REV JI Endocr. Rev. PD JUN PY 2014 VL 35 IS 3 SU S MA OR36-4 PG 2 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA V45GM UT WOS:000209805107236 ER PT J AU Takasawa, K Pelosi, E Takagi, M Morio, T Asahara, H Schlessinger, D Mizutani, S Koopman, P Kashimada, K AF Takasawa, Kei Pelosi, Emanuele Takagi, Masatoshi Morio, Tomohiro Asahara, Hiroshi Schlessinger, David Mizutani, Shuki Koopman, Peter Kashimada, Kenichi TI FOXL2 Transcriptionally Represses Sf1 Expression By Antagonizing WT1 during Ovarian Development in Mice SO ENDOCRINE REVIEWS LA English DT Meeting Abstract C1 [Takasawa, Kei; Takagi, Masatoshi; Morio, Tomohiro; Asahara, Hiroshi; Mizutani, Shuki; Kashimada, Kenichi] Tokyo Med & Dent Univ, Tokyo, Japan. [Pelosi, Emanuele; Schlessinger, David] NIA, NIH, Biomed Res Ctr, Intramural Res Program, Bethesda, MD 20892 USA. [Koopman, Peter] Univ Queensland, Brisbane, Qld, Australia. NR 3 TC 0 Z9 0 U1 0 U2 0 PU ENDOCRINE SOC PI WASHINGTON PA 2055 L ST NW, SUITE 600, WASHINGTON, DC 20036 USA SN 0163-769X EI 1945-7189 J9 ENDOCR REV JI Endocr. Rev. PD JUN PY 2014 VL 35 IS 3 SU S MA SAT-0113 PG 2 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA V45GM UT WOS:000209805107246 ER PT J AU Thearle, MS Schlogl, M Bonfiglio, SM Krakoff, J AF Thearle, Marie S. Schlogl, Mathias Bonfiglio, Susan M. Krakoff, Jonathan TI Energy Expenditure Response to 24 Hours of Overfeeding and Fasting Are Related to Adiposity SO ENDOCRINE REVIEWS LA English DT Meeting Abstract C1 [Thearle, Marie S.] NIDDK, NIH, Phoenix, AZ USA. [Schlogl, Mathias; Bonfiglio, Susan M.; Krakoff, Jonathan] NIDDK, Phoenix Epidemiol & Clin Res Branch, NIH, Phoenix, AZ USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ENDOCRINE SOC PI WASHINGTON PA 2055 L ST NW, SUITE 600, WASHINGTON, DC 20036 USA SN 0163-769X EI 1945-7189 J9 ENDOCR REV JI Endocr. Rev. PD JUN PY 2014 VL 35 IS 3 SU S MA OR16-3 PG 2 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA V45GM UT WOS:000209805103137 ER PT J AU Tiano, JP Springer, DA Rane, SG AF Tiano, Joseph P. Springer, Danielle A. Rane, Sushil G. TI Transforming Growth Factor-Beta Is Negatively Associated with Irisin in Exercised Obese Mice SO ENDOCRINE REVIEWS LA English DT Meeting Abstract C1 [Tiano, Joseph P.; Springer, Danielle A.; Rane, Sushil G.] NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ENDOCRINE SOC PI WASHINGTON PA 2055 L ST NW, SUITE 600, WASHINGTON, DC 20036 USA SN 0163-769X EI 1945-7189 J9 ENDOCR REV JI Endocr. Rev. PD JUN PY 2014 VL 35 IS 3 SU S MA SUN-0349 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA V45GM UT WOS:000209805100236 ER PT J AU Tuna, MM Karakilic, E Basaran, MN Dogan, BA Imga, NN Arduc, A Tutuncu, Y Unal, T Berker, D Guler, S AF Tuna, Mazhar Muslum Karakilic, Ersen Basaran, Mehtap Navdar Dogan, Bercem Aycicek Imga, Narin Nasiroglu Arduc, Ayse Tutuncu, Yasemin Unal, Tuba Berker, Dilek Guler, Serdar TI Evaluation of Immunohistochemical Staining Features in Acromegaly Patients- Comparing with Clinical Findings SO ENDOCRINE REVIEWS LA English DT Meeting Abstract C1 [Tuna, Mazhar Muslum; Dogan, Bercem Aycicek; Imga, Narin Nasiroglu; Unal, Tuba; Berker, Dilek] Ankara Numune Training & Res Hosp, Ankara, Turkey. [Karakilic, Ersen; Basaran, Mehtap Navdar] Ankara Numune Educ & Training Hosp, Ankara, Turkey. [Arduc, Ayse] NIDDK, Diabet Endocrine & Obes Branch, NIH, Bethesda, MD 20892 USA. [Tutuncu, Yasemin] Haydarpasa Numune Training & Res Hosp, Istanbul, Turkey. [Guler, Serdar] Hitit Univ, Fac Med, Corum, Turkey. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ENDOCRINE SOC PI WASHINGTON PA 2055 L ST NW, SUITE 600, WASHINGTON, DC 20036 USA SN 0163-769X EI 1945-7189 J9 ENDOCR REV JI Endocr. Rev. PD JUN PY 2014 VL 35 IS 3 SU S MA SUN-0620 PG 3 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA V45GM UT WOS:000209805101020 ER PT J AU van Berkel, A Rao, JU Kusters, B Demir, T Visser, E Mensenkamp, A van der Laak, JAWM Oosterwijk, E Lenders, JW Sweep, FCGJ Wevers, RA Hermus, ARMM Langenhuijzen, HJF Kunst, HPM Pacak, K Gotthardt, M Timmers, HJLM AF van Berkel, Anouk Rao, Jyotsna U. Kusters, Benno Demir, Tuna Visser, Erik Mensenkamp, Arjen van der Laak, Jeroen A. W. M. Oosterwijk, Egbert Lenders, Jacques W. M. Sweep, Fred C. G. J. Wevers, Ron A. Hermus, Ad R. M. M. Langenhuijzen, Hans J. F. Kunst, Henricus P. M. Pacak, Karel Gotthardt, Martin Timmers, Henri J. L. M. TI Correlation Between in Vivo 18F-Fluorodeoxyglucose PET and lmmunohistochemical Markers of Glucose Uptake and Metabolism in Pheochromocytoma and Paraganglioma SO ENDOCRINE REVIEWS LA English DT Meeting Abstract C1 [van Berkel, Anouk; Rao, Jyotsna U.; Visser, Erik; van der Laak, Jeroen A. W. M.; Hermus, Ad R. M. M.; Timmers, Henri J. L. M.] Radboud Univ Nijmegen, Med Ctr, Nijmegen, Netherlands. [Kusters, Benno; Demir, Tuna; Mensenkamp, Arjen; Oosterwijk, Egbert; Sweep, Fred C. G. J.; Wevers, Ron A.; Langenhuijzen, Hans J. F.; Kunst, Henricus P. M.; Gotthardt, Martin] Radboud Univ Nijmegen, Med Ctr, Nijmegen, Netherlands. [Lenders, Jacques W. M.] Raboud Univ, Med Ctr, Nijmegen, Netherlands. [Pacak, Karel] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, NIH, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ENDOCRINE SOC PI WASHINGTON PA 2055 L ST NW, SUITE 600, WASHINGTON, DC 20036 USA SN 0163-769X EI 1945-7189 J9 ENDOCR REV JI Endocr. Rev. PD JUN PY 2014 VL 35 IS 3 SU S MA PP14-1 PG 2 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA V45GM UT WOS:000209805100181 ER PT J AU van Berkel, A Rao, JU Kusters, B Demir, T Visser, E Mensenkamp, A van der Laak, JAWM Oosterwijk, E Lenders, JWM Sweep, FCGJ Wevers, RA Hermus, ARMM Langenhuijzen, HJF Kunst, HPM Pacak, K Gotthardt, M Timmers, HJLM AF van Berkel, Anouk Rao, Jyotsna U. Kusters, Benno Demir, Tuna Visser, Erik Mensenkamp, Arjen van der Laak, Jeroen A. W. M. Oosterwijk, Egbert Lenders, Jacques W. M. Sweep, Fred C. G. J. Wevers, Ron A. Hermus, Ad R. M. M. Langenhuijzen, Hans J. F. Kunst, Henricus P. M. Pacak, Karel Gotthardt, Martin Timmers, Henri J. L. M. TI Correlation Between in Vivo 18F-Fluorodeoxyglucose PET and lmmunohistochemical Markers of Glucose Uptake and Metabolism in Pheochromocytoma and Paraganglioma SO ENDOCRINE REVIEWS LA English DT Meeting Abstract C1 [van Berkel, Anouk; Rao, Jyotsna U.; Visser, Erik; van der Laak, Jeroen A. W. M.; Lenders, Jacques W. M.; Hermus, Ad R. M. M.; Timmers, Henri J. L. M.] Radboud Univ Nijmegen, Med Ctr, Nijmegen, Netherlands. [Kusters, Benno; Demir, Tuna; Mensenkamp, Arjen; Oosterwijk, Egbert; Sweep, Fred C. G. J.; Wevers, Ron A.; Langenhuijzen, Hans J. F.; Kunst, Henricus P. M.; Gotthardt, Martin] Radboud Univ Nijmegen, Med Ctr, Nijmegen, Netherlands. [Pacak, Karel] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, NIH, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ENDOCRINE SOC PI WASHINGTON PA 2055 L ST NW, SUITE 600, WASHINGTON, DC 20036 USA SN 0163-769X EI 1945-7189 J9 ENDOCR REV JI Endocr. Rev. PD JUN PY 2014 VL 35 IS 3 SU S MA SUN-0798 PG 3 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA V45GM UT WOS:000209805101329 ER PT J AU Venturutti, L Russo, RIC Yankilevich, P Oakley, RH Huang, THM Schillaci, R Cidlowski, JA Elizalde, PV AF Venturutti, Leandro Cordo Russo, Rosalia Inas Yankilevich, Patricio Oakley, Robert H. Huang, Tim H-M Schillaci, Roxana Cidlowski, John A. Virginia Elizalde, Patricia TI Tumor Suppressor Mir-16 Mediates Trastuzumab Therapeutic Effects in Breast Cancer Via Its Novel Targets, Cyclin J (CCNJ) and Fuse Binding Protein 1 (FUBP1) SO ENDOCRINE REVIEWS LA English DT Meeting Abstract C1 [Venturutti, Leandro; Cordo Russo, Rosalia Inas; Schillaci, Roxana; Virginia Elizalde, Patricia] Consejo Nacl Invest Cient & Tecn, Inst Biol & Med Expt, Buenos Aires, DF, Argentina. [Yankilevich, Patricio] IBIOBA CONICET MPSP, Buenos Aires, DF, Argentina. [Oakley, Robert H.] Natl Inst Environm Hlth Sci, Res Triangle Pk, NC USA. [Huang, Tim H-M] Univ Texas Hlth Sci Ctr San Antonio, San Antonio, TX 78229 USA. NIEHS NIH, Res Triangle Pk, NC USA. NR 2 TC 0 Z9 0 U1 0 U2 0 PU ENDOCRINE SOC PI WASHINGTON PA 2055 L ST NW, SUITE 600, WASHINGTON, DC 20036 USA SN 0163-769X EI 1945-7189 J9 ENDOCR REV JI Endocr. Rev. PD JUN PY 2014 VL 35 IS 3 SU S MA SAT-0318 PG 3 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA V45GM UT WOS:000209805108126 ER PT J AU Xekouki, P Zilbermint, M Faucz, FR Lodish, MB Berthon, AS Schernthaner-Reiter, MH Hodes, A Sierra, MDLL Bertherat, JY Stratakis, CA AF Xekouki, Paraskevi Zilbermint, Mihail Faucz, Fabio Rueda Lodish, Maya Beth Berthon, Annabel Sophie Schernthaner-Reiter, Marie Helene Hodes, Aaron Sierra, Maria De La Luz Bertherat, Jerome Yves Stratakis, Constantine A. TI Mutations of ARMC5 Gene May be Implicated in Primary Hyperaldosteronism (PA) SO ENDOCRINE REVIEWS LA English DT Meeting Abstract C1 [Xekouki, Paraskevi; Zilbermint, Mihail; Faucz, Fabio Rueda; Lodish, Maya Beth; Berthon, Annabel Sophie; Schernthaner-Reiter, Marie Helene; Sierra, Maria De La Luz; Stratakis, Constantine A.] NIH, Bethesda, MD 20892 USA. [Hodes, Aaron] Drexel Univ, Coll Med, Philadelphia, PA 19104 USA. [Bertherat, Jerome Yves] CNRS, INSERM, Unite 1016, Unite Mixte Rech 8104,Inst Cochin, Paris, France. NR 3 TC 0 Z9 0 U1 0 U2 0 PU ENDOCRINE SOC PI WASHINGTON PA 2055 L ST NW, SUITE 600, WASHINGTON, DC 20036 USA SN 0163-769X EI 1945-7189 J9 ENDOCR REV JI Endocr. Rev. PD JUN PY 2014 VL 35 IS 3 SU S MA SAT-0841 PG 3 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA V45GM UT WOS:000209805106109 ER PT J AU Yang, RF Tsai-Morris, CH Dufau, ML AF Yang, Ruifeng Tsai-Morris, Chon-Hwa Dufau, Maria L. TI Elucidation of RNA Binding Regions of Gonadotropin Regulated Testicular RNA Helicase (GRTH/DDX25) Protein to Transcripts of a Chromatin Remodeling Protein Essential for Spermatogenesis SO ENDOCRINE REVIEWS LA English DT Meeting Abstract C1 [Yang, Ruifeng; Tsai-Morris, Chon-Hwa] NIH, Bethesda, MD 20892 USA. [Dufau, Maria L.] NICHD, NIH, Bethesda, MD USA. NR 4 TC 0 Z9 0 U1 0 U2 0 PU ENDOCRINE SOC PI WASHINGTON PA 2055 L ST NW, SUITE 600, WASHINGTON, DC 20036 USA SN 0163-769X EI 1945-7189 J9 ENDOCR REV JI Endocr. Rev. PD JUN PY 2014 VL 35 IS 3 SU S MA MON-0100 PG 2 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA V45GM UT WOS:000209805107258 ER PT J AU Yanovski, JA Lee, BG Koo, J Gavrilova, O Taylor-Douglas, D Roberson, R Koutzoumis, D AF Yanovski, Jack A. Lee, Bong Gi Koo, JaShin Gavrilova, Oksana Taylor-Douglas, Dezmond Roberson, Robin Koutzoumis, Dimitri TI Studies of Mechanisms for Pediatric Obesity Due to Melanocortin 3 Receptor (MC3R) Insufficiency Using Knock-in Mice Expressing Human Wild Type MC3R or Thr6Lys+Va1811Ie Human Variant MC3R SO ENDOCRINE REVIEWS LA English DT Meeting Abstract C1 [Yanovski, Jack A.; Lee, Bong Gi; Koo, JaShin; Taylor-Douglas, Dezmond; Roberson, Robin; Koutzoumis, Dimitri] NIH, Bethesda, MD 20892 USA. [Gavrilova, Oksana] NIDDK, NIH, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ENDOCRINE SOC PI WASHINGTON PA 2055 L ST NW, SUITE 600, WASHINGTON, DC 20036 USA SN 0163-769X EI 1945-7189 J9 ENDOCR REV JI Endocr. Rev. PD JUN PY 2014 VL 35 IS 3 SU S MA OR53-2 PG 2 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA V45GM UT WOS:000209805104134 ER PT J AU Yuditskaya, S Gounden, V Soldin, S Celi, FS AF Yuditskaya, Susan Gounden, Verena Soldin, Steven Celi, Francesco S. TI Low Serum Triiodothyronine Levels Associated with Symptomatic Hypothyroidism in an Athyreotic Patient on Adequate Levothyroxine Replacement SO ENDOCRINE REVIEWS LA English DT Meeting Abstract C1 [Yuditskaya, Susan; Gounden, Verena; Soldin, Steven] NIH, Bethesda, MD 20892 USA. [Celi, Francesco S.] NIDDKD, NIH, Bethesda, MD USA. NR 1 TC 0 Z9 0 U1 0 U2 0 PU ENDOCRINE SOC PI WASHINGTON PA 2055 L ST NW, SUITE 600, WASHINGTON, DC 20036 USA SN 0163-769X EI 1945-7189 J9 ENDOCR REV JI Endocr. Rev. PD JUN PY 2014 VL 35 IS 3 SU S MA SAT-0522 PG 3 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA V45GM UT WOS:000209805108264 ER PT J AU Yuditskaya, S Sharma, ST Nieman, LK AF Yuditskaya, Susan Sharma, Susmeeta T. Nieman, Lynnette K. TI Ectopic Corticotropinoma or ACTH-Secreting Breast Cancer Metastasis? SO ENDOCRINE REVIEWS LA English DT Meeting Abstract C1 [Yuditskaya, Susan; Nieman, Lynnette K.] NIH, Bethesda, MD 20892 USA. [Sharma, Susmeeta T.] Eunice Kennedy Shrivel Natl Inst Child Hlth & Hum, NIH, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ENDOCRINE SOC PI WASHINGTON PA 2055 L ST NW, SUITE 600, WASHINGTON, DC 20036 USA SN 0163-769X EI 1945-7189 J9 ENDOCR REV JI Endocr. Rev. PD JUN PY 2014 VL 35 IS 3 SU S MA SAT-0662 PG 3 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA V45GM UT WOS:000209805101101 ER PT J AU Zilbermint, M Faucz, FR Lodish, MB Szarek, E Trivellin, G Sinaii, N Libe, R Assie, G Espiard, S Drougat, L Ragazzon, B Bertherat, JY Stratakis, CA AF Zilbermint, Mihail Faucz, Fabio Rueda Lodish, Maya Beth Szarek, Eva Trivellin, Giampaolo Sinaii, Ninet Libe, Rossella Assie, Guillaume Espiard, Stephanie Drougat, Ludivine Ragazzon, Bruno Bertherat, Jerome Yves Stratakis, Constantine A. TI Macronodular Adrenal Hyperplasia Due to Mutations in an Armadillo Repeat Containing 5 (ARMC5) Gene: A Clinical and Genetic Investigation SO ENDOCRINE REVIEWS LA English DT Meeting Abstract C1 [Zilbermint, Mihail; Faucz, Fabio Rueda; Lodish, Maya Beth; Szarek, Eva; Trivellin, Giampaolo; Sinaii, Ninet; Stratakis, Constantine A.] NIH, Bethesda, MD 20892 USA. [Libe, Rossella; Assie, Guillaume; Espiard, Stephanie; Drougat, Ludivine; Ragazzon, Bruno; Bertherat, Jerome Yves] Inst Cochin, INSERM, Unite 1016, CNRS,UMR 8104, Paris, France. NR 4 TC 0 Z9 0 U1 0 U2 0 PU ENDOCRINE SOC PI WASHINGTON PA 2055 L ST NW, SUITE 600, WASHINGTON, DC 20036 USA SN 0163-769X EI 1945-7189 J9 ENDOCR REV JI Endocr. Rev. PD JUN PY 2014 VL 35 IS 3 SU S MA OR14-1 PG 3 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA V45GM UT WOS:000209805102217 ER PT J AU Zilbermint, M Hodes, A Lodish, MB Sinaii, N Belyavskaya, E Lyssikatos, C Rosenberg, K Meyer, J Stratakis, CA AF Zilbermint, Mihail Hodes, Aaron Lodish, Maya Beth Sinaii, Ninet Belyavskaya, Elena Lyssikatos, Charalampos Rosenberg, Kendra Meyer, Jerrold Stratakis, Constantine A. TI Hair Cortisol Measurement in the Evaluation of Cushing's Syndrome: A Pilot Study SO ENDOCRINE REVIEWS LA English DT Meeting Abstract C1 [Zilbermint, Mihail; Lodish, Maya Beth; Sinaii, Ninet; Belyavskaya, Elena; Lyssikatos, Charalampos; Stratakis, Constantine A.] NIH, Bethesda, MD 20892 USA. [Hodes, Aaron] Drexel Univ, Coll Med, Philadelphia, PA 19104 USA. [Rosenberg, Kendra; Meyer, Jerrold] Univ Massachusetts, Amherst, MA 01003 USA. NR 4 TC 0 Z9 0 U1 0 U2 0 PU ENDOCRINE SOC PI WASHINGTON PA 2055 L ST NW, SUITE 600, WASHINGTON, DC 20036 USA SN 0163-769X EI 1945-7189 J9 ENDOCR REV JI Endocr. Rev. PD JUN PY 2014 VL 35 IS 3 SU S MA MON-0658 PG 3 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA V45GM UT WOS:000209805101280 ER PT J AU Zuber, S Wesley, R Eisenhofer, G Pacak, K Kantorovich, V AF Zuber, Samuel Wesley, Robert Eisenhofer, Graeme Pacak, Karel Kantorovich, Vitaly TI Clinical Utility of Chromogranin a in Sdhx-Related Paragangliomas SO ENDOCRINE REVIEWS LA English DT Meeting Abstract C1 [Zuber, Samuel; Pacak, Karel] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, NIH, Bethesda, MD USA. [Wesley, Robert] NIH, Bethesda, MD USA. [Eisenhofer, Graeme] Univ Hosp Carl Gustav Carus, Dresden, Germany. [Kantorovich, Vitaly] Univ Connecticut, Ctr Hlth, Farmington, CT USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ENDOCRINE SOC PI WASHINGTON PA 2055 L ST NW, SUITE 600, WASHINGTON, DC 20036 USA SN 0163-769X EI 1945-7189 J9 ENDOCR REV JI Endocr. Rev. PD JUN PY 2014 VL 35 IS 3 SU S MA OR27-1 PG 2 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA V45GM UT WOS:000209805100070 ER PT J AU Ghosh, G Grewal, J Mannisto, T Mendola, P Chen, Z Xie, YL Laughon, SK AF Ghosh, Gaurav Grewal, Jagteshwar Mannisto, Tuija Mendola, Pauline Chen, Zhen Xie, Yunlong Laughon, S. Katherine TI RACIAL/ETHNIC DIFFERENCES IN PREGNANCY-RELATED HYPERTENSIVE DISEASE IN NULLIPAROUS WOMEN SO ETHNICITY & DISEASE LA English DT Article DE Ethnic Groups; Hypertension; Pregnancy-induced; Pre-eclampsia ID RISK-FACTORS; MATERNAL HYPERTENSION; HISPANIC WOMEN; PREECLAMPSIA; POPULATION; OUTCOMES; COHORT; COMPLICATIONS; DISPARITIES; MANAGEMENT AB Objective: Hypertension and cardiovascular disease rates vary by race/ethnicity in nonpregnant adults. We aimed to examine racial/ethnic differences in prevalence and severity of hypertensive diseases during pregnancy in nulliparous women. Design, Setting, Participants: Nulliparous women with singleton deliveries and electronic medical record data on demographics and pregnancy outcomes (n=56,617) were selected from the Consortium on Safe Labor (2002-2008). Multivariable logistic regression was performed to calculate the adjusted odds of gestational hypertension, mild preeclampsia, severe preeclampsia, eclampsia, chronic hypertension, superimposed preeclampsia, and unspecified hypertension for women who were non-Hispanic Black, Hispanic, Asian/Pacific Islander, and multiracial/other race/ethnicity, compared with non-Hispanic White women. Results: Non-Hispanic Black women had higher odds of entering pregnancy with chronic hypertension (adjusted odds ratio (AOR) =1.43, 95% confidence interval (CI) 1.11-1.84) and had higher odds of developing mild (AOR=1.26, 95% CI 1.10-1.45), severe (AOR=1.31, 95% CI 1.10-1.57) or superimposed preeclampsia (AOR=1.98, 95% CI 1.40-2.80) compared to non-Hispanic White women. Hispanic women and Asian/Pacific Islanders had higher odds of remaining normotensive (AOR=1.22, 95% CI 1.12-1.33 and AOR=1.55, 95% CI 1.31-1.84, respectively). Conclusions: Odds for specific gestational hypertensive diseases varied by race/ethnicity among women during their first pregnancy. Non-Hispanic Black women experienced more severe disease, while Hispanic women and Asian/Pacific Islanders had an overall decreased risk compared to non-Hispanic Whites. Patterns of racial/ethnic variation associated with hypertensive diseases during pregnancy were similar to racial/ethnic associations reported for adultonset cardiovascular disease, suggesting that there may be common pathways and shared risk factors. C1 [Ghosh, Gaurav; Grewal, Jagteshwar; Mannisto, Tuija; Mendola, Pauline; Laughon, S. Katherine] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Epidemiol Branch, NIH, Rockville, MD 20852 USA. [Chen, Zhen; Xie, Yunlong] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Biostat & Bioinformat Branch, NIH, Rockville, MD 20852 USA. RP Laughon, SK (reprint author), Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Epidemiol Branch, Div Intramural Populat Hlth Res, NIH, 6100 Execut Blvd,Room 7B03, Rockville, MD 20852 USA. EM laughonsk@mail.nih.gov OI Grewal, Jagteshwar/0000-0002-0141-4876; Mendola, Pauline/0000-0001-5330-2844; Grantz, Katherine/0000-0003-0276-8534 FU Intramural Research Program of the Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health [HHSN267200603425C] FX The Consortium on Safe Labor was supported by the Intramural Research Program of the Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, through Contract No. HHSN267200603425C. NR 30 TC 6 Z9 6 U1 1 U2 3 PU INT SOC HYPERTENSION BLACKS-ISHIB PI ATLANTA PA 100 AUBURN AVE NE STE 401, ATLANTA, GA 30303-2527 USA SN 1049-510X EI 1945-0826 J9 ETHNIC DIS JI Ethn. Dis. PD SUM PY 2014 VL 24 IS 3 BP 283 EP 289 PG 7 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA CU7KT UT WOS:000363717300003 PM 25065068 ER PT J AU Walker, ER Nelson, CR Antoine-LaVigne, D Thigpen, DT Puggal, MA Sarpong, DF Smith, AM Stewart, AL Henderson, FC AF Walker, Evelyn R. Nelson, Cheryl R. Antoine-LaVigne, Donna Thigpen, Darcel T. Puggal, Mona A. Sarpong, Daniel F. Smith, Alice M. Stewart, Alyce L. Henderson, Frances C. TI RESEARCH PARTICIPANTS' OPINIONS ON GENETIC RESEARCH AND REASONS FOR PARTICIPATION: A JACKSON HEART STUDY FOCUS GROUP ANALYSIS SO ETHNICITY & DISEASE LA English DT Article DE Community-based Participatory Research; Genetics; Ethics; Community Education ID AFRICAN-AMERICANS; RECRUITMENT AB The Jackson Heart Study (JHS) convened focus groups to engage the community in dialogue on participation in the National, Heart, Lung and Blood Institute's Candidate Gene Resource (CARe) project. CARe, a genome wide association and candidate gene study, required the release of participant phenotypic and genotypic data with storage at NIH for widespread distribution to qualified researchers. The authors wanted to assess the willingness of an African American community to participate in the genetics research, given the past history of bioethical misconduct in ethnic minority communities. The discussion produced the following specific issues of interest: reasons for participants' interest in genetics research; participants' knowledge about the JHS; and participants' knowledge about genetics research and its advantages and disadvantages. Training on genetic issues was also developed for the JHS community and staff. C1 [Walker, Evelyn R.] Mississippi Dept Hlth, Ridgeland, MS 39157 USA. [Nelson, Cheryl R.; Puggal, Mona A.] NHLBI, NIH, Bethesda, MD USA. [Antoine-LaVigne, Donna; Sarpong, Daniel F.; Smith, Alice M.; Stewart, Alyce L.] Jackson State Univ, Jackson, MS 39217 USA. [Henderson, Frances C.] Univ Mississippi, Med Ctr, University, MS 38677 USA. RP Walker, ER (reprint author), Mississippi Dept Hlth, Off Hlth Promot & Hlth Equ, Ridgeland, MS 39157 USA. EM Evelyn.Walker@msdh.ms.gov FU National Heart, Lung, and Blood Institute [HHSN268201300046C, HHSN268201300047C, HHSN268201300048C, HHSN268201300049C, HHSN268201300050C]; National Institute on Minority Health and Health Disparities FX The Jackson Heart Study is supported by contracts HHSN268201300046C, HHSN268201300047C, HHSN268201300048C, HHSN268201300049C, HHSN268201300050C from the National Heart, Lung, and Blood Institute and the National Institute on Minority Health and Health Disparities. We also acknowledge Doris Withers, PhD Medgar Evers College, School of Science, Health, and Technology (Biology Department) for her guidance with the focus groups and in completing this manuscript. NR 19 TC 1 Z9 1 U1 0 U2 0 PU INT SOC HYPERTENSION BLACKS-ISHIB PI ATLANTA PA 100 AUBURN AVE NE STE 401, ATLANTA, GA 30303-2527 USA SN 1049-510X EI 1945-0826 J9 ETHNIC DIS JI Ethn. Dis. PD SUM PY 2014 VL 24 IS 3 BP 290 EP 297 PG 8 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA CU7KT UT WOS:000363717300004 PM 25065069 ER PT J AU McLean, MH Hanson, ML Gold, B Golubeva, Y Anver, MR Wu, X Sun, D Steidler, L Durum, SK AF McLean, M. H. Hanson, M. L. Gold, B. Golubeva, Y. Anver, M. R. Wu, X. Sun, D. Steidler, L. Durum, S. K. TI INTRA-LUMINAL INTERLEUKIN (IL)-27 IS A POTENTIAL FUTURE THERAPEUTIC FOR INFLAMMATORY BOWEL DISEASE SO GUT LA English DT Meeting Abstract CT Annual Meeting of the British-Society-of-Gastroenterology (BSG) CY JUN 16-19, 2014 CL Manchester, ENGLAND SP British Soc Gastroenterol C1 [McLean, M. H.; Hanson, M. L.; Durum, S. K.] NCI, Canc & Inflammat Program, Bethesda, MD 20892 USA. [Gold, B.] NCI, Human Genet Sect, Bethesda, MD 20892 USA. [Golubeva, Y.; Anver, M. R.] Leidos Biomedical Res Inc, Lab Anim Sci Program, Frederick Natl Lab Canc Res, Frederick, MD USA. [Wu, X.; Sun, D.] Leidos Biomedical Res Inc, Lab Mol Technol, Frederick Natl Lab Canc Res, Frederick, MD USA. [Steidler, L.] ActoGenix NV, Zwijnaarde, Belgium. NR 0 TC 1 Z9 1 U1 1 U2 2 PU BMJ PUBLISHING GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 0017-5749 EI 1468-3288 J9 GUT JI Gut PD JUN PY 2014 VL 63 SU 1 MA PTU-103 BP A84 EP A84 DI 10.1136/gutjnl-2014-307263.177 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA CO8OF UT WOS:000359428500179 ER PT J AU Finegold, J Bordachar, P Kyriacou, A Sohaib, SMA Kanagaratnam, P Ploux, S Lim, B Peters, N Davies, DW Lefroy, D Ritter, P Francis, D Whinnett, Z AF Finegold, Judith Bordachar, Pierre Kyriacou, Andreas Sohaib, S. M. Afzal Kanagaratnam, Prapa Ploux, Sylvain Lim, Boon Peters, Nicholas Davies, David Wyn Lefroy, David Ritter, Philippe Francis, Darrel Whinnett, Zachary TI CORRELATION AND REPRODUCIBILITY OF INVASIVE AND NON-INVASIVE HAEMODYNAMIC PARAMETERS FOR IDENTIFYING OPTIMAL AV DELAY IN CARDIAC RESYNCHRONISATION THERAPY SO HEART LA English DT Meeting Abstract CT Annual Conference of the British-Cardiovascular-Society CY JUN 02-04, 2014 CL Manchester, ENGLAND SP British Cardiovascular Soc C1 [Finegold, Judith; Kyriacou, Andreas; Sohaib, S. M. Afzal; Francis, Darrel; Whinnett, Zachary] Natl Heart & Lung Inst, Int Ctr Circulatory Hlth, Bethesda, MD USA. [Bordachar, Pierre; Ploux, Sylvain; Ritter, Philippe] Hop Haut Leveque, Pessac, France. [Kanagaratnam, Prapa; Lim, Boon; Peters, Nicholas; Davies, David Wyn; Lefroy, David] Imperial Coll, London, England. NR 0 TC 0 Z9 0 U1 0 U2 0 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 JUN PY 2014 VL 100 SU 3 MA 41 BP A22 EP A23 DI 10.1136/heartjnl-2014-306118.41 PG 3 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA CP5UR UT WOS:000359951000042 ER PT J AU Finegold, J Cazeau, S Sohaib, SMA Kyriacou, A Manisty, C Ritter, P Bordachar, P Whinnett, Z Francis, D AF Finegold, Judith Cazeau, Serge Sohaib, S. M. Afzal Kyriacou, Andreas Manisty, Charlotte Ritter, Philippe Bordachar, Pierre Whinnett, Zachary Francis, Darrel TI THE EFFECT OF ALTERING AV DELAY ON THE PRE-EJECTION PERIOD IN PATIENTS WITH BIVENTRICULAR PACEMAKERS SO HEART LA English DT Meeting Abstract CT Annual Conference of the British-Cardiovascular-Society CY JUN 02-04, 2014 CL Manchester, ENGLAND SP British Cardiovascular Soc C1 [Finegold, Judith; Sohaib, S. M. Afzal; Kyriacou, Andreas; Manisty, Charlotte; Whinnett, Zachary; Francis, Darrel] Natl Heart & Lung Inst, Int Ctr Circulatory Hlth, Bethesda, MD USA. [Cazeau, Serge] Paris St Joseph, Dept Rythmol, Paris, France. [Ritter, Philippe; Bordachar, Pierre] Hop Haut Leveque, Pessac, France. NR 0 TC 0 Z9 0 U1 0 U2 0 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 JUN PY 2014 VL 100 SU 3 MA 40 BP A22 EP A22 DI 10.1136/heartjnl-2014-306118.40 PG 1 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA CP5UR UT WOS:000359951000041 ER PT J AU Crous, PW Giraldo, A Hawksworth, DL Robert, V Kirk, PM Guarro, J Robbertse, B Schoch, CL Damm, U Trakunyingcharoen, T Groenewald, JZ AF Crous, Pedro W. Giraldo, Alejandra Hawksworth, David L. Robert, Vincent Kirk, Paul M. Guarro, Josep Robbertse, Barbara Schoch, Conrad L. Damm, Ulrike Trakunyingcharoen, Thippawan Groenewald, Johannes Z. TI The Genera of Fungi: fixing the application of type species of generic names SO IMA FUNGUS LA English DT Article DE DNA Barcodes; fungal systematic; ITS; LSU; typification; www.GeneraofFungi.org AB To ensure a stable platform for fungal taxonomy, it is of paramount importance that the genetic application of generic names be based on their DNA sequence data, and wherever possible, not morphology or ecology alone. To facilitate this process, a new database, accessible at www.GeneraofFungi.org (GoF) was established, which will allow deposition of metadata linked to holo-, lecto-, neo- or epitype specimens, cultures and DNA sequence data of the type species of genera. Although there are presently more than 18 000 fungal genera described, we aim to initially focus on the subset of names that have been placed on the "Without-prejudice List of Protected Generic Names of Fungi" (see IMA Fungus 4(2): 381-443, 2013). To enable the global mycological community to keep track of typification events and avoid duplication, special MycoBank Typification identfiers (MBT) will be issued upon deposit of metadata in MycoBank. MycoBank is linked to GoF, thus deposited metadata of generic type species will be displayed in GoF (and vice versa), but will also be linked to Index Fungorum (IF) and the curated RefSeq Targeted Loci (RTL) database in GenBank at the National Center for Biotechnology Information (NCBI). This initial paper focuses on eight genera of appendaged coelomycetes, the type species of which are neo- or epitypified here: Bartalinia (Bartalinia robillardoides; Amphisphaeriaceae, Xylariales), Chaetospermum (Chaetospermum chaetosporum, incertae sedis, Sebacinales), Coniella (Coniella fragariae, Schizoparmaceae, Diaporthales), Crinitospora (Crinitospora pulchra, Melanconidaceae, Diaporthales), Eleutheromyces (Eleutheromyces subulatus, Helotiales), Kellermania (Kellermania yuccigena, Planistromataceae, Botryosphaeriales), Mastigosporium (Mastigosporium album, Helotiales), and Mycotribulus (Mycotribulus mirabilis, Agaricales). Authors interested in contributing accounts of individual genera to larger multi-authored papers to be published in IMA Fungus, should contact the associate editors listed below for the major groups of fungi on the List of Protected Generic Names for Fungi. C1 [Crous, Pedro W.; Robert, Vincent; Groenewald, Johannes Z.] CBS KNAW Fungal Biodivers Ctr, Uppsalalaan 8, NL-3584 CT Utrecht, Netherlands. [Crous, Pedro W.] Univ Utrecht, Dept Biol, Microbiol, NL-3584 CT Utrecht, Netherlands. [Crous, Pedro W.] Wageningen Univ & Res Ctr WUR, Lab Phytopathol, NL-6708 PB Wageningen, Netherlands. [Giraldo, Alejandra; Guarro, Josep] Univ Rovira & Virgili, Fac Med & Ciencies Salut, Unitat Micol, Tarragona, Spain. [Giraldo, Alejandra; Guarro, Josep] Univ Rovira & Virgili, IISPV, Tarragona, Spain. [Hawksworth, David L.] Univ Complutense Madrid, Fac Farm, Dept Biol Vegetal 2, E-28040 Madrid, Spain. [Hawksworth, David L.] Nat Hist Museum, Dept Life Sci, London SW7 5BD, England. [Hawksworth, David L.; Kirk, Paul M.] Royal Bot Gardens, Mycol Sect, Richmond TW9 3DS, Surrey, England. [Kirk, Paul M.] Chinese Acad Sci, Inst Microbiol, State Key Lab Mycol, Beijing 100101, Peoples R China. [Robbertse, Barbara; Schoch, Conrad L.] NIH, Natl Ctr Biotechnol Informat, Natl Lib Med, Bethesda, MD 20892 USA. [Damm, Ulrike] Senckenberg Museum Nat Hist Gorlitz, D-02806 Gorlitz, Germany. [Trakunyingcharoen, Thippawan] Chiang Mai Univ, Fac Agr, Dept Entomol & Plant Pathol, Chiang Mai 50200, Thailand. RP Crous, PW (reprint author), CBS KNAW Fungal Biodivers Ctr, Uppsalalaan 8, NL-3584 CT Utrecht, Netherlands. EM p.crous@cbs.knaw.nl RI Groenewald, Johannes/F-4667-2011; Crous, Pedro/H-1489-2012; OI Crous, Pedro/0000-0001-9085-8825; Guarro, Josep/0000-0002-7839-7568 FU Royal Golden Jubilee Ph.D. Programme [PHD/0353/2552]; Spanish Ministerio de Economia y Competitividad [CGL 2011-27185]; Intramural Research Program of the NIH, National Library of Medicine FX We thank the technical staff, Arien van Iperen (cultures), Marjan Vermaas (photographic plates), and Mieke Starink-Willemse (DNA isolation, amplification and sequencing) for their invaluable assistance. Thippawan Trakunyingcharoen acknowledges financial support from the Royal Golden Jubilee Ph.D. Programme (Grant No. PHD/0353/2552). Alejandra Giraldo Lopez is grateful for the financial support received from the Spanish Ministerio de Economia y Competitividad, grant CGL 2011-27185. Conrad L. Schoch and Barbara Robbertse acknowledge support from the Intramural Research Program of the NIH, National Library of Medicine. NR 78 TC 16 Z9 17 U1 1 U2 9 PU INT MYCOLOGICAL ASSOC PI BERKELEY PA C/O J TAYLOR, DEPT PLANT & MICROBIAL BIOLOGY, BERKELEY, CA 94720 USA SN 2210-6340 EI 2210-6359 J9 IMA FUNGUS JI IMA Fungus PD JUN PY 2014 VL 5 IS 1 BP 141 EP 160 DI 10.5598/imafungus.2014.05.01.14 PG 20 WC Mycology SC Mycology GA V46UJ UT WOS:000209908800028 PM 25083414 ER PT J AU Moten, A Schafer, D Farmer, P Kim, J Ferrari, M AF Moten, Asad Schafer, Daniel Farmer, Paul Kim, Jim Ferrari, Mauro TI Redefining global health priorities: Improving cancer care in developing settings SO JOURNAL OF GLOBAL HEALTH LA English DT Editorial Material C1 [Moten, Asad; Schafer, Daniel] Healthnovat Int, Inst Translat Med & Novel Therapeut, Houston, TX 77089 USA. [Moten, Asad] Univ Oxford, Nuffield Dept Clin Med, Dept Primary Care Hlth Sci, Oxford, England. [Moten, Asad; Ferrari, Mauro] Natl Canc Inst Alliance Nanotechnol Canc, NIH, Bethesda, MD USA. [Farmer, Paul] Harvard Univ, Sch Med, Harvard Global Hlth Inst, Boston, MA USA. [Kim, Jim] WHO Int Agcy Res Canc, World Bank, United Nations Dev Grp, New York, NY USA. [Ferrari, Mauro] Alliance NanoHlth, Dept Nanomed, Houston Methodist Res Inst, Houston, TX USA. RP Moten, A (reprint author), Healthnovat Int, 12403 Salama Falls, Houston, TX 77089 USA. EM aimoten@gmail.com FU World Health Organization [001] NR 14 TC 3 Z9 3 U1 0 U2 3 PU UNIV EDINBURGH, GLOBAL HEALTH SOC PI EDINBURGH PA CENTRE POPULATION HEALTH SCIENCES, TEVIOT PL, EDINBURGH, EH8 9AG, ENGLAND SN 2047-2978 EI 2047-2986 J9 J GLOB HEALTH JI J. Glob. Health PD JUN PY 2014 VL 4 IS 1 AR 010304 DI 10.7189/jogh.04.010304 PG 5 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA V42SJ UT WOS:000209633200005 PM 24976959 ER PT J AU Burch, PT Gerstenberger, E Ravishankar, C Hehir, DA Davies, RR Colan, SD Sleeper, LA Newburger, JW Clabby, ML Williams, IA Li, JS Uzark, K Cooper, DS Lambert, LM Pemberton, VL Pike, NA Anderson, JB Dunbar-Masterson, C Khaikin, S Zyblewski, SC Minich, LL AF Burch, Phillip T. Gerstenberger, Eric Ravishankar, Chitra Hehir, David A. Davies, Ryan R. Colan, Steven D. Sleeper, Lynn A. Newburger, Jane W. Clabby, Martha L. Williams, Ismee A. Li, Jennifer S. Uzark, Karen Cooper, David S. Lambert, Linda M. Pemberton, Victoria L. Pike, Nancy A. Anderson, Jeffrey B. Dunbar-Masterson, Carolyn Khaikin, Svetlana Zyblewski, Sinai C. Minich, L. Luann CA Pediat Heart Network Investigators TI Longitudinal Assessment of Growth in Hypoplastic Left Heart Syndrome: Results From the Single Ventricle Reconstruction Trial SO JOURNAL OF THE AMERICAN HEART ASSOCIATION LA English DT Article DE growth; hypoplastic left heart syndrome; pediatrics; risk factors AB Background-We sought to characterize growth between birth and age 3 years in infants with hypoplastic left heart syndrome who underwent the Norwood procedure. Methods and Results-We performed a secondary analysis using the Single Ventricle Reconstruction Trial database after excluding patients <37 weeks gestation (N=498). We determined length-for-age z score (LAZ) and weight-for-age z score (WAZ) at birth and age 3 years and change in WAZ over 4 clinically relevant time periods. We identified correlates of change in WAZ and LAZ using multivariable linear regression with bootstrapping. Mean WAZ and LAZ were below average relative to the general population at birth (P<0.001, P=0.05, respectively) and age 3 years (P<0.001 each). The largest decrease in WAZ occurred between birth and Norwood discharge; the greatest gain occurred between stage II and 14 months. At age 3 years, WAZ and LAZ were <-2 in 6% and 18%, respectively. Factors associated with change in WAZ differed among time periods. Shunt type was associated with change in WAZ only in the Norwood discharge to stage II period; subjects with a Blalock-Taussig shunt had a greater decline in WAZ than those with a right ventricle-pulmonary artery shunt (P=0.002). Conclusions-WAZ changed over time and the predictors of change in WAZ varied among time periods. By age 3 years, subjects remained small and three times as many children were short as were underweight (>2 SD below normal). Failure to find consistent risk factors supports the strategy of tailoring nutritional therapies to patient-and stage-specific targets. C1 [Burch, Phillip T.; Lambert, Linda M.] Univ Utah, Dept Surg, Salt Lake City, UT USA. [Minich, L. Luann] Univ Utah, Dept Pediat, Salt Lake City, UT USA. [Gerstenberger, Eric; Sleeper, Lynn A.] New England Res Inst, Watertown, MA 02172 USA. [Ravishankar, Chitra] Childrens Hosp Philadelphia, Philadelphia, PA 19104 USA. [Hehir, David A.] Childrens Hosp Wisconsin, Milwaukee, WI 53201 USA. [Davies, Ryan R.] Nemours AI DuPont Hosp Children, Wilmington, DE USA. [Colan, Steven D.; Newburger, Jane W.; Dunbar-Masterson, Carolyn] Childrens Hosp Boston, Boston, MA USA. [Colan, Steven D.; Newburger, Jane W.; Dunbar-Masterson, Carolyn] Harvard Univ, Sch Med, Boston, MA USA. [Clabby, Martha L.; Khaikin, Svetlana] Hosp Sick Children, Toronto, ON M5G 1X8, Canada. [Williams, Ismee A.] Columbia Univ, Med Ctr, New York, NY USA. [Li, Jennifer S.] Duke Univ, Med Ctr, Durham, NC USA. [Uzark, Karen] Univ Michigan, Sch Med, Ann Arbor, MI USA. [Cooper, David S.; Anderson, Jeffrey B.] Univ Cincinnati, Cincinnati, OH USA. [Pemberton, Victoria L.] NIH, Bethesda, MD 20892 USA. [Pike, Nancy A.] Univ Calif Los Angeles, Los Angeles, CA USA. [Zyblewski, Sinai C.] Med Univ S Carolina, Charleston, SC 29425 USA. RP Burch, PT (reprint author), Primary Childrens Med Ctr, Div Cardiothorac Surg, 100 North Mario Capecchi Dr, Salt Lake City, UT 84113 USA. EM Phillip.Burch@hsc.utah.edu OI Davies, Ryan/0000-0003-4631-9685 FU National Heart, Lung, and Blood Institute [HL068269, HL068270, HL068279, HL068281, HL068285, HL068292, HL068290, HL068288, HL085057] FX Supported by U01 grants from the National Heart, Lung, and Blood Institute (HL068269, HL068270, HL068279, HL068281, HL068285, HL068292, HL068290, HL068288, HL085057). NR 31 TC 9 Z9 9 U1 1 U2 2 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 2047-9980 J9 J AM HEART ASSOC JI J. Am. Heart Assoc. PD JUN PY 2014 VL 3 IS 3 AR e000079 DI 10.1161/JAHA.114.000079 PG 15 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA V41RD UT WOS:000209562400004 PM 24958780 ER PT J AU Hunter, CM McKinnon, RA Esposito, L AF Hunter, C. M. McKinnon, R. A. Esposito, L. TI News from the NIH: research to evaluate "natural experiments" related to obesity and diabetes SO TRANSLATIONAL BEHAVIORAL MEDICINE LA English DT News Item ID BODY-MASS INDEX; UNITED-STATES; PREVALENCE; CHILDREN; TRENDS C1 [Hunter, C. M.] NIDDKD, Bethesda, MD 20892 USA. [McKinnon, R. A.] NCI, Bethesda, MD 20892 USA. [Esposito, L.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Bethesda, MD USA. RP Hunter, CM (reprint author), NIDDKD, Bethesda, MD 20892 USA. NR 14 TC 5 Z9 5 U1 1 U2 1 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 JUN PY 2014 VL 4 IS 2 BP 127 EP 129 DI 10.1007/s13142-013-0250-z PG 3 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA CL2PL UT WOS:000356786400001 PM 24904694 ER PT J AU Zhu, ZH Yin, YF Zheng, K Li, F Chen, XY Zhang, FC Zhang, X AF Zhu, Zhaohui Yin, Yufeng Zheng, Kun Li, Fang Chen, Xiaoyuan Zhang, Fengchun Zhang, Xuan TI Evaluation of synovial angiogenesis in patients with rheumatoid arthritis using Ga-68-PRGD2 PET/CT: a prospective proof-of-concept cohort study SO ANNALS OF THE RHEUMATIC DISEASES LA English DT Article ID DISEASE-ACTIVITY; INTEGRIN; CANCER; EXPRESSION; ADHESION; TARGET AB Background The study aimed to evaluate the use of positron emission tomography/computed tomography (PET/CT) with Ga-68-PRGD2 as the tracer for imaging of synovial angiogenesis in patients with rheumatoid arthritis (RA). Methods Twenty untreated active patients with RA underwent Ga-68-PRGD2 PET/CT and F-18-FDG PET/CT before treatment; two patients with osteoarthritis served as controls. Among the 20 patients with RA, 12 repeated the evaluations after 3-month treatment. The image findings were correlated with core variables of disease activity, including the clinical disease activity index (cDAI). Results Our findings demonstrated that Ga-68-PRGD2 specifically accumulated in the synovia with active inflammation rich in neovasculature with high-level alpha(v)beta(3)-integrin expression, but not in the F-18-FDG-avid inflammatory lymph nodes. In patients with intense F-18-FDG uptake in muscles caused by arthritic pain, we observed that Ga-68-PRGD2 PET/CT was better able to evaluate disease severity than F-18-FDG PET/CT. Both Ga-68-PRGD2 accumulation and F-18-FDG uptake changed in response to therapeutic intervention, whereas the changes of Ga-68-PRGD2, not F-18-FDG, significantly correlated with clinical measures of changes in the form of cDAI. Conclusions This is the first integrin imaging study conducted in patients with RA that preliminarily indicates the effectiveness of the novel method for evaluating synovial angiogenesis. C1 [Zhu, Zhaohui; Zheng, Kun; Li, Fang] Chinese Acad Med Sci, Dept Nucl Med, Peking Union Med Coll Hosp, Beijing 100730, Peoples R China. [Zhu, Zhaohui; Yin, Yufeng; Zheng, Kun; Li, Fang; Zhang, Fengchun; Zhang, Xuan] Peking Union Med Coll, Beijing 100730, Peoples R China. [Yin, Yufeng; Zhang, Fengchun; Zhang, Xuan] Chinese Acad Med Sci, Dept Rheumatol, Peking Union Med Coll Hosp, Beijing 100730, Peoples R China. [Chen, Xiaoyuan] Natl Inst Biomed Imaging & Bioengn, Lab Mol Imaging & Nanomed, NIH, Bethesda, MD USA. RP Zhang, X (reprint author), Chinese Acad Med Sci, Dept Rheumatol, Peking Union Med Coll Hosp, 1 Shuaifuyuan,Wangfujing St, Beijing 100730, Peoples R China. EM zhuzhh@pumch.cn; zxpumch2003@sina.com FU National Natural Science Foundation of China [81325019, 81171370, 81172859, 81271614, 81273312, 81371596]; National High Technology Research and Development Project of China [2011AA020111, 2012AA02A513]; National Major Scientific and Technological Special Project [2012ZX09303006-002]; National Basic Research Program of China (973 program) [2013CB733802, 2014CB744503]; Research Special Fund for Public Welfare Industry of Health [201202004]; Capital Health Research and Development of Special Foundation [2011-4001-02]; Capital Special Project for Featured Clinical Application [Z121107001012119]; National Laboratory Special Fund [2060204]; Intramural Research Program (IRP); National Institute of Biomedical Imaging and Bioengineering (NIBIB); National Institutes of Health (NIH); Beijing Municipal Natural Science Foundation [7141008] FX This study was funded in part by the National Natural Science Foundation of China (81325019, 81171370, 81172859, 81271614, 81273312, 81371596), the National High Technology Research and Development Project of China (2011AA020111, 2012AA02A513), the National Major Scientific and Technological Special Project (2012ZX09303006-002), the National Basic Research Program of China (973 program 2013CB733802, 2014CB744503), the Research Special Fund for Public Welfare Industry of Health (201202004), the Capital Health Research and Development of Special Foundation (2011-4001-02), the Capital Special Project for Featured Clinical Application (Z121107001012119), the National Laboratory Special Fund (2060204), the Intramural Research Program (IRP), National Institute of Biomedical Imaging and Bioengineering (NIBIB) and National Institutes of Health (NIH) and Beijing Municipal Natural Science Foundation (7141008). NR 20 TC 16 Z9 17 U1 2 U2 8 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 JUN PY 2014 VL 73 IS 6 BP 1269 EP 1272 DI 10.1136/annrheumdis-2013-204820 PG 4 WC Rheumatology SC Rheumatology GA AG4AW UT WOS:000335362100056 PM 24532680 ER PT J AU Auer, DR Sysa-Shah, P Bedja, D Simmers, JL Pak, E Dutra, A Cohn, R Gabrielson, KL Chakravarti, A Kapoor, A AF Auer, Dallas R. Sysa-Shah, Polina Bedja, Djahida Simmers, Jessica L. Pak, Evgenia Dutra, Amalia Cohn, Ronald Gabrielson, Kathleen L. Chakravarti, Aravinda Kapoor, Ashish TI Generation of a cre recombinase-conditional Nos1ap over-expression transgenic mouse SO BIOTECHNOLOGY LETTERS LA English DT Article DE Cardiac arrhythmia; Conditional over-expression; GENOME-wide association studies; NOS1AP; QT interval; Sudden cardiac death; Transgenic mouse ID NITRIC-OXIDE SYNTHASE; QT INTERVAL DURATION; MODULATES CARDIAC REPOLARIZATION; COMMON VARIANTS; CAPON; CELLS; PROTEIN; GENE; CHROMOSOME; DEATH AB Polymorphic non-coding variants at the NOS1AP locus have been associated with the common cardiac, metabolic and neurological traits and diseases. Although, in vitro gene targeting-based cellular and biochemical studies have shed some light on NOS1AP function in cardiac and neuronal tissue, to enhance our understanding of NOS1AP function in mammalian physiology and disease, we report the generation of cre recombinase-conditional Nos1ap over-expression transgenic mice (Nos1ap (Tg)). Conditional transgenic mice were generated by the pronuclear injection method and three independent, single-site, multiple copies integration event-based founder lines were selected. For heart-restricted over-expression, Nos1ap (Tg) mice were crossed with Mlc2v-cre and Nos1ap transcript over-expression was observed in left ventricles from Nos1ap (Tg); Mlc2v-cre F-1 mice. We believe that with the potential of conditional over-expression, Nos1ap (Tg) mice will be a useful resource in studying NOS1AP function in various tissues under physiological and disease states. C1 [Auer, Dallas R.; Simmers, Jessica L.; Chakravarti, Aravinda; Kapoor, Ashish] Johns Hopkins Univ, Sch Med, McKusick Nathans Inst Genet Med, Baltimore, MD 21205 USA. [Sysa-Shah, Polina; Bedja, Djahida; Gabrielson, Kathleen L.] Johns Hopkins Univ, Sch Med, Dept Mol & Comparat Pathobiol, Baltimore, MD 21205 USA. [Pak, Evgenia; Dutra, Amalia] NHGRI, NIH, Bethesda, MD 20892 USA. [Cohn, Ronald] Univ Toronto, Hosp Sick Children, Toronto, ON M5G 1X8, Canada. RP Chakravarti, A (reprint author), Johns Hopkins Univ, Sch Med, McKusick Nathans Inst Genet Med, 733 N Broadway, Baltimore, MD 21205 USA. EM psysa1@jhmi.edu; dbedja1@jhmi.edu; jlsimmers@gmail.com; epak@mail.nih.gov; adutra@mail.nih.gov; ronald.cohn@sickkids.ca; kgabriel@jhmi.edu; aravinda@jhmi.edu; ashish@jhmi.edu FU Donald R. Reynolds Foundation; National Institutes of Health FX We are grateful to Dr. Andras Nagy (Mount Sinai Hospital, Toronto) for providing the pCLIP vector and to Dr. Kenneth Chien (Massachusetts General Hospital, Boston) for providing the Mlc2v-cre mice. We are thankful to Dr. Gordon Tomaselli, Dr. David Kass and Gary Steel (Johns Hopkins University, Baltimore) for critical discussions. This work was supported in part by funds from the Donald R. Reynolds Foundation and the National Institutes of Health. NR 26 TC 1 Z9 1 U1 0 U2 6 PU SPRINGER PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 0141-5492 EI 1573-6776 J9 BIOTECHNOL LETT JI Biotechnol. Lett. PD JUN PY 2014 VL 36 IS 6 BP 1179 EP 1185 DI 10.1007/s10529-014-1473-x PG 7 WC Biotechnology & Applied Microbiology SC Biotechnology & Applied Microbiology GA AG0ZY UT WOS:000335145800007 PM 24563304 ER PT J AU Hirsch, DS Shen, Y Dokmanovic, M Yu, J Mohan, N Elzarrad, MK Wu, WJ AF Hirsch, Dianne S. Shen, Yi Dokmanovic, Milos Yu, Joyce Mohan, Nishant Elzarrad, Mohammed Khair Wu, Wen Jin TI Insulin activation of vacuolar protein sorting 34 mediates localized phosphatidylinositol 3-phosphate production at lamellipodia and activation of mTOR/S6K1 SO CELLULAR SIGNALLING LA English DT Article DE Class III phosphatidylinositol 3-kinase/vacuolar protein sorting 34 (VPS34); Insulin; Src; ptdins(3)p; S6 kinase 1 (S6K1); mTOR ID MAMMALIAN-CELLS; TYROSINE PHOSPHORYLATION; ACTIN CYTOSKELETON; S6 KINASE; 3-KINASE; RESISTANCE; MOTILITY; INSIGHTS; HVPS34; GROWTH AB The class III phosphatidylinositol 3-kinase, VPS34, phosphorylates the 03 hydroxyl of inositol generating phosphatidylinositol 3-phosphate (ptdins(3)p). Initial studies suggested that ptdins(3)p solely functioned as a component of vesicular and endosomal membranes and that VPS34 did not function in signal transduction. However, VPS34 has recently been shown to be required for insulin-mediated activation of S6 kinase 1 (S6K1). Whether VPS34 activity is directly regulated by insulin is unclear. It is also not known whether VPS34 activity can be spatially restricted in response to extracellular stimuli. Data presented here demonstrate that in response to insulin, VPS34 is activated and translocated to lamellipodia where it produces ptdins(3)p. The localized production of ptdins(3)p is dependent on Src phosphorylation of VPS34.1n cells expressing VPS34 with mutations at Y231 or Y310, which are Src-phosphorylation sites, insulin-stimulated VPS34 translocation to the plasma membrane and lamellipodia formation are blocked. mTOR also colocalizes with VPS34 and ptdins(3)p at lamellipodia following insulin-stimulation. In cells expressing the VPS34-Y231F mutant, which blocks lamellipodia formation, mTOR localization at the plasma membrane and insulin-mediated S6K1 activation are reduced. This suggests that mTOR localization at lamellipodia is important for full activation of S6K1 induced by insulin. These data demonstrate that insulin can spatially regulate VPS34 activity through Src-mediated tyrosine phosphorylation and that this membrane localized activity contributes to lamellipodia formation and activation of mTOR/S6K1signaling. Published by Elsevier Inc. C1 [Hirsch, Dianne S.; Shen, Yi; Dokmanovic, Milos; Yu, Joyce; Mohan, Nishant; Elzarrad, Mohammed Khair; Wu, Wen Jin] US FDA, Div Monoclonal Antibodies, Off Biotechnol Prod, Off Pharmaceut Sci,Ctr Drug Evaluat & Res, Bethesda, MD 20892 USA. [Elzarrad, Mohammed Khair] NCI, Interagency Oncol Task Force IOTF Fellowship Prog, NIH, Bethesda, MD 20892 USA. RP Wu, WJ (reprint author), US FDA, Div Monoclonal Antibodies, Off Biotechnol Prod, Off Pharmaceut Sci,Ctr Drug Evaluat & Res, HFD 123,29B Lincoln Dr,Room 3NN20, Bethesda, MD 20892 USA. EM wen.wu@fda.hhs.gov NR 37 TC 3 Z9 4 U1 0 U2 5 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0898-6568 EI 1873-3913 J9 CELL SIGNAL JI Cell. Signal. PD JUN PY 2014 VL 26 IS 6 BP 1258 EP 1268 DI 10.1016/j.cellsig.014.02.009 PG 11 WC Cell Biology SC Cell Biology GA AG0OH UT WOS:000335114300011 PM 24582588 ER PT J AU Boularan, C Kehrl, JH AF Boularan, Cedric Kehrl, John H. TI Implications of non-canonical G-protein signaling for the immune system SO CELLULAR SIGNALLING LA English DT Review DE G-protein signaling; Immune system; Ric-8A; Non-canonical ID HETEROTRIMERIC G-PROTEINS; PASTEURELLA-MULTOCIDA TOXIN; GUANINE-NUCLEOTIDE EXCHANGE; ASYMMETRIC CELL-DIVISION; CONTROLS AUTOPHAGIC SEQUESTRATION; CYSTEINE-STRING-PROTEIN; T-LYMPHOCYTE DIVISION; N-TERMINAL KINASE; G-ALPHA-I; C-BETA 1 AB Heterotrimeric guanine nucleotide-binding proteins (G proteins), which consist of three subunits alpha, beta and gamma, function as molecular switches to control downstream effector molecules activated by G protein-coupled receptors (GPCRs). The GTP/GDP binding status of G alpha transmits information about the ligand binding state of the GPCR to intended signal transduction pathways. In immune cells heterotrimeric G proteins impact signal transduction pathways that directly, or indirectly, regulate cell migration, activation, survival, proliferation, and differentiation. The cells of the innate and adaptive immune sykem abundantly express chemoattractant receptors and lesser amounts of many other types of GPCRs. But heterotrimeric G-proteins not only function in classical GPCR signaling, but also in non-canonical signaling. In these pathways the guanine exchange factor (GEF) exerted by a GPCR in the canonical pathway is replaced or supplemented by another protein such as Ric-8A. In addition, other proteins such as AGS3-6 can compete with G beta gamma for binding to GDP bound G alpha. This competition can promote G beta gamma signaling by freeing G beta gamma from rapidly rebinding GDP bound G alpha. The proteins that participate in these non-canonical signaling pathways will be briefly described and their role, or potential one, in cells of the immune system will be highlighted. Published by Elsevier Inc. C1 [Boularan, Cedric; Kehrl, John H.] NIAID, B Cell Mol Immunol Sect, Immunoregulat Lab, NIH, Bethesda, MD 20892 USA. RP Kehrl, JH (reprint author), NIAID, Immunoregulat Lab, NIH, Bldg 10,Room 11B08,10 Ctr Dr MSC 1876, Bethesda, MD 20892 USA. EM jkehrl@niaid.nih.gov OI Kehrl, John/0000-0002-6526-159X FU Intramural Research Program of the National Institute of Allergy and Infectious Diseases; National Institutes of Health FX The authors would like to thank Dr. Anthony Fauci for his continued support. This work benefitted from data assembled by ImmGen consortium. This research was supported by the Intramural Research Program of the National Institute of Allergy and Infectious Diseases, National Institutes of Health. NR 171 TC 10 Z9 10 U1 1 U2 11 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0898-6568 EI 1873-3913 J9 CELL SIGNAL JI Cell. Signal. PD JUN PY 2014 VL 26 IS 6 BP 1269 EP 1282 DI 10.1016/j.cellsig.014.02.010 PG 14 WC Cell Biology SC Cell Biology GA AG0OH UT WOS:000335114300012 PM 24583286 ER PT J AU Aliev, G Priyadarshini, M Reddy, VP Grieg, NH Kaminsky, Y Cacabelos, R Ashraf, GM Jabir, NR Kamal, MA Nikolenko, VN Zamyatnin, AA Benberin, VV Bachurin, SO AF Aliev, G. Priyadarshini, M. Reddy, V. P. Grieg, N. H. Kaminsky, Y. Cacabelos, R. Ashraf, G. Md Jabir, N. R. Kamal, M. A. Nikolenko, V. N. Zamyatnin, A. A., Jr. Benberin, V. V. Bachurin, S. O. TI Oxidative Stress Mediated Mitochondrial and Vascular Lesions as Markers in the Pathogenesis of Alzheimer Disease SO CURRENT MEDICINAL CHEMISTRY LA English DT Article DE Alzheimer disease; antioxidants; cerebrovascular pathology; mitochondria; neurodegeneration; oxidative stress ID ACETYL-L-CARNITINE; MILD COGNITIVE IMPAIRMENT; ALPHA-LIPOIC-ACID; CHRONIC CEREBRAL HYPOPERFUSION; AMYLOID PRECURSOR PROTEIN; TARGETED ANTIOXIDANT MITOQ; NEURODEGENERATIVE DISEASES; MOUSE MODEL; OLD RATS; ENDOTHELIAL DYSFUNCTION AB Mitochondrial dysfunction plausibly underlies the aging-associated brain degeneration. Mitochondria play a pivotal role in cellular bioenergetics and cell-survival. Oxidative stress consequent to chronic hypoperfusion induces mitochondrial damage, which is implicated as the primary cause of cerebrovascular accidents (CVA) mediated Alzheimer's disease (AD). The mitochondrial function deteriorates with aging, and the mitochondrial damage correlates with increased intracellular production of oxidants and pro-oxidants. The prolonged oxidative stress and the resultant hypoperfusion in the brain tissues stimulate the expression of nitric oxide synthase (NOS) enzymes, which further drives the formation of reactive oxygen species (ROS) and reactive nitrogen species (RNS). The ROS and RNS collectively contributes to the dysfunction of the blood-brain barrier (BBB) and damage to the brain parenchymal cells. Delineating the molecular mechanisms of these processes may provide clues for the novel therapeutic targets for CVA and AD patients. C1 [Aliev, G.] GALLY Int Biomed Res Consulting LLC, San Antonio, TX 78229 USA. [Aliev, G.] Univ Atlanta, Sch Hlth Sci & Healthcare Adm, Johns Creek, GA 30097 USA. [Priyadarshini, M.] Aligarh Muslim Univ, Fac Life Sci, Dept Biochem, Aligarh 202002, Uttar Pradesh, India. [Reddy, V. P.] Missouri Univ Sci & Technol, Dept Chem, Rolla, MO 65409 USA. [Grieg, N. H.] NIA, Drug Design & Dev Sect, Lab Neurosci, Intramural Res Program,NIH, Baltimore, MD 21224 USA. [Kaminsky, Y.] Russian Acad Sci, Inst Theoret & Expt Biophys, Pushchino 142290, Russia. [Cacabelos, R.] Inst CNS Disorders & Genom Med, EuroEspes Biomed Res Ctr, Bergondo 15165, La Coruna, Spain. [Cacabelos, R.] Camilo Jose Cela Univ, Bergondo 15165, La Coruna, Spain. [Ashraf, G. Md; Jabir, N. R.; Kamal, M. A.] King Abdulaziz Univ, King Fahd Med Res Ctr, Jeddah 21589, Saudi Arabia. [Nikolenko, V. N.] Sechenov First Moscow State Med Univ, Dept Anat, Moscow 119991, Russia. [Zamyatnin, A. A., Jr.] Sechenov First Moscow State Med Univ, Inst Mol Med, Moscow 119991, Russia. [Benberin, V. V.] Med Ctr Adm President Republ Kazakhstan, Astana 010000, Kazakhstan. [Bachurin, S. O.] Russian Acad Sci, Inst Physiol Act Cpds, Chernogolovka 142432, Moscow Region, Russia. RP Aliev, G (reprint author), GALLY Int Biomed Res Consulting LLC, 7733 Louis Pasteur Dr,330, San Antonio, TX 78229 USA. EM aliev03@gmail.com RI Zamyatnin, Andrey/D-6443-2012; Ashraf, Ghulam Md/H-9485-2012; Rehumathbeevi, Jabir/H-9483-2012; OI Zamyatnin, Andrey/0000-0002-3046-4565; Ashraf, Ghulam Md/0000-0002-9820-2078; Rehumathbeevi, Jabir/0000-0001-8548-7986; Kamal, Mohammad Amjad/0000-0003-0088-0565 FU GALLY International Biomedical Research Consulting LLC, San Antonio, Texas, USA FX We thank Ms. Galina Alieva for her editorial work. These studies were partially supported by the GALLY International Biomedical Research Consulting LLC, San Antonio, Texas, USA. Dr. Medha Priyadarshini is an incumbent of DST-INSPIRE Faculty Award, Dept. of Science and Technology, Govt. of India. Thanks are due to DSR and KFMRC (King Abdulaziz University, Jeddah, Saudi Arabia) for the facilities. NR 159 TC 49 Z9 55 U1 5 U2 39 PU BENTHAM SCIENCE PUBL LTD PI SHARJAH PA EXECUTIVE STE Y-2, PO BOX 7917, SAIF ZONE, 1200 BR SHARJAH, U ARAB EMIRATES SN 0929-8673 EI 1875-533X J9 CURR MED CHEM JI Curr. Med. Chem. PD JUN PY 2014 VL 21 IS 19 BP 2208 EP 2217 PG 10 WC Biochemistry & Molecular Biology; Chemistry, Medicinal; Pharmacology & Pharmacy SC Biochemistry & Molecular Biology; Pharmacology & Pharmacy GA AG4MF UT WOS:000335393300010 PM 24372221 ER PT J AU Liu, XD Wang, XL Bai, X Liu, XL Wu, XP Zhao, Y Sun, SM Yu, L Su, XZ Wang, ZQ Wang, F Liu, MY AF Liu, X. D. Wang, X. L. Bai, X. Liu, X. L. Wu, X. P. Zhao, Y. Sun, S. M. Yu, L. Su, X. Z. Wang, Z. Q. Wang, F. Liu, M. Y. TI Oral administration with attenuated Salmonella encoding a Trichinella cystatin-like protein elicited host immunity SO EXPERIMENTAL PARASITOLOGY LA English DT Article DE Trichinella spiralis; Cystatin-like protein; Attenuated Salmonella; Th1/Th2; Immunosuppressive; Eukaryotic expression system ID GUT EPITHELIAL MONOLAYERS; PHOP-VIRULENCE REGULON; PROTECTIVE IMMUNITY; TYPHIMURIUM VIRULENCE; GENE-THERAPY; DNA VACCINES; T-BET; SPIRALIS; CELLS; ENTERICA AB Trichinellosis is a public health problem and is regarded as an emergent/re-emergent disease in various countries. The cDNA encoding a cystatin-like protein (Ts-cystatin) was identified by immunoscreening intestinal muscle larvae cDNA libraries with serum from pigs experimentally infected with 20,000 Trichinella spiralis muscle larvae. To study its impact on host immunity, we chose a eukaryotic expression system based on several comparisons of immunogenicity between the two Salmonella typhimurium administration schemes, which indicated that the eukaryotic expression system was superior. Humoral IgG and mucosal IgA were measured to determine the antibody response. To explore whether Th1 and Th2 responses were responsible for the induced protection, Th1- and Th2-specific cellular transcription factors and the cytokine profile were examined. Changes in the T lymphocyte and macrophage populations were detected by flow cytometry. Lastly, parasitological examination was examined. The results showed that Ts-cystatin induced a Th1/Th2-mixed type of immune response and decreased STAT6 transcription. The intestinal adult recovery increased by 10.9% in the Ts-cystatin group, the Ts-cystatin group fecundity rate was decreased by 91%. Furthermore, the number of muscle larvae did not change compared with the control group. In conclusion, our results suggest that Ts-cystatin plays an important role in Trichinella resistance to rapid expulsion by the host and is worth further study. (C) 2014 Elsevier Inc. All rights reserved. C1 [Liu, X. D.; Wang, X. L.; Bai, X.; Liu, X. L.; Zhao, Y.; Sun, S. M.; Yu, L.; Wang, F.; Liu, M. Y.] Jilin Univ, Inst Zoonosis, Key Lab Zoonoses Res, Minist Educ, Changchun 130062, Peoples R China. [Wu, X. P.] Natl Inst Parasit Dis, Chinese Ctr Dis Control & Prevent, Shanghai 200025, Peoples R China. [Liu, M. Y.] Jiangsu Coinnovat Ctr Prevent & Control Important, Yangzhou 225009, Peoples R China. [Su, X. Z.] NIAID, Lab Malaria & Vector Res, NIH, Bethesda, MD 20892 USA. [Wang, Z. Q.] Zhengzhou Univ, Coll Med, Dept Parasitol, Zhengzhou 450052, Peoples R China. RP Wu, XP (reprint author), Jilin Univ, Inst Zoonosis, Key Lab Zoonoses Res, Minist Educ, Changchun 130062, Peoples R China. EM xpwu@jlu.edu.cn; zhaoyingsohu@sohu.com; liumy@jlu.edu.cn OI Su, Xinzhuan/0000-0003-3246-3248 FU Ministry of Science and Technology of China [MOST 2011AA10A215]; Postdoctoral fund in China [2012M520683]; National Natural Science Foundation of China [NSFC 31030064, 30972177, 81070311, 31072124] FX This work was supported by grants from the Ministry of Science and Technology of China (MOST 2011AA10A215), Postdoctoral fund in China (2012M520683) and the National Natural Science Foundation of China (NSFC 31030064, 30972177, 81070311, 31072124). NR 41 TC 9 Z9 9 U1 0 U2 9 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0014-4894 EI 1090-2449 J9 EXP PARASITOL JI Exp. Parasitol. PD JUN PY 2014 VL 141 BP 1 EP 11 DI 10.1016/j.exppara.2014.03.015 PG 11 WC Parasitology SC Parasitology GA AG6QD UT WOS:000335542600001 PM 24636891 ER PT J AU Daye, PM Optican, LM Blohm, G Lefevre, P AF Daye, Pierre M. Optican, Lance M. Blohm, Gunnar Lefevre, Philippe TI Hierarchical control of two-dimensional gaze saccades SO JOURNAL OF COMPUTATIONAL NEUROSCIENCE LA English DT Article DE Gaze saccades; Eye; Head; Feedback control; Superior colliculus; VOR suppression ID EYE-HEAD COORDINATION; CAUDAL FASTIGIAL NUCLEUS; MONKEY SUPERIOR COLLICULUS; VESTIBULOOCULAR REFLEX SUPPRESSION; STEM OMNIPAUSE NEURONS; MUSCIMOL INACTIVATION; REVERSIBLE INACTIVATION; UNRESTRAINED CAT; TECTORETICULOSPINAL NEURONS; MOVEMENT KINEMATICS AB Coordinating the movements of different body parts is a challenging process for the central nervous system because of several problems. Four of these main difficulties are: first, moving one part can move others; second, the parts can have different dynamics; third, some parts can have different motor goals; and fourth, some parts may be perturbed by outside forces. Here, we propose a novel approach for the control of linked systems with feedback loops for each part. The proximal parts have separate goals, but critically the most distal part has only the common goal. We apply this new control policy to eye-head coordination in two-dimensions, specifically head-unrestrained gaze saccades. Paradoxically, the hierarchical structure has controllers for the gaze and the head, but not for the eye (the most distal part). Our simulations demonstrate that the proposed control structure reproduces much of the published empirical data about gaze movements, e.g., it compensates for perturbations, accurately reaches goals for gaze and head from arbitrary initial positions, simulates the nine relationships of the head-unrestrained main sequence, and reproduces observations from lesion and single-unit recording experiments. We conclude by showing how our model can be easily extended to control structures with more linked segments, such as the control of coordinated eye on head on trunk movements. C1 [Daye, Pierre M.; Optican, Lance M.] NEI, NIH, Sensorimotor Res Lab, Bethesda, MD 20892 USA. [Blohm, Gunnar] Queens Univ, Ctr Neurosci Studies, Kingston, ON K7L 3N6, Canada. [Lefevre, Philippe] UCLouvain, ICTeam, IoNS, B-1348 Louvain, Belgium. RP Daye, PM (reprint author), NEI, NIH, Sensorimotor Res Lab, 49 Convent Dr,Room 2A50, Bethesda, MD 20892 USA. EM pierre.daye@gmail.com; lanceoptican@nih.gov; gunnar.blohm@queensu.ca; philippe.lefevre@uclouvain.be FU Intramural Research Program of the National Eye Institute; National Science and Engineering Research Council (Canada); Ontario Research Fund (Canada); Canadian Foundation for Innovation (Canada); Botterell Foundation (Queens University, Kingston, ON, Canada); Fonds National de la Recherche Scientifique, Action de Recherche Concertee (Belgium); Interuniversity Attraction Poles Programmes; Belgian State, Science Policy Office FX Drs. Optican and Daye were supported by the Intramural Research Program of the National Eye Institute.; Dr. Blohm has been supported by the National Science and Engineering Research Council (Canada), the Ontario Research Fund (Canada), the Canadian Foundation for Innovation (Canada) and the Botterell Foundation (Queens University, Kingston, ON, Canada).; Dr. Lefevre has been supported by Fonds National de la Recherche Scientifique, Action de Recherche Concertee (Belgium). This paper presents research results of the Belgian Network Dynamical Systems, Control and Optimization, funded by the Interuniversity Attraction Poles Programmes, initiated by the Belgian State, Science Policy Office. NR 94 TC 8 Z9 8 U1 1 U2 8 PU SPRINGER PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 0929-5313 EI 1573-6873 J9 J COMPUT NEUROSCI JI J. Comput. Neurosci. PD JUN PY 2014 VL 36 IS 3 BP 355 EP 382 DI 10.1007/s10827-013-0477-1 PG 28 WC Mathematical & Computational Biology; Neurosciences SC Mathematical & Computational Biology; Neurosciences & Neurology GA AG2JA UT WOS:000335241100003 PM 24062206 ER PT J AU Vogtmann, E Shu, XO Li, HL Chow, WH Yang, G Ji, BT Cai, H Yu, C Gao, YT Zheng, W Xiang, YB AF Vogtmann, Emily Shu, Xiao-Ou Li, Hong-Lan Chow, Wong-Ho Yang, Gong Ji, Bu-Tian Cai, Hui Yu, Chang Gao, Yu-Tang Zheng, Wei Xiang, Yong-Bing TI Cholelithiasis and the risk of liver cancer: results from cohort studies of 134 546 Chinese men and women SO JOURNAL OF EPIDEMIOLOGY AND COMMUNITY HEALTH LA English DT Article ID SEVERE GALLSTONE DISEASE; EXTRAHEPATIC CHOLANGIOCARCINOMA; CHOLECYSTECTOMY; POPULATION; EPIDEMIOLOGY; TAIWAN; HEALTH AB Background Cholelithiasis and cholecystectomy have been proposed as risk factors for liver cancer, but findings have been inconsistent. We assessed this association using data from the Shanghai Women's and Men's Health Studies. Methods History of cholelithiasis and cholecystectomy were reported at baseline and follow-up interviews, and liver cancer diagnoses were ascertained from the Shanghai Cancer Registry and Vital Statistics Unit. Adjusted hazard ratios (aHRs) and 95% CIs were calculated after adjustment for potential confounders. Results A history of cholelithiasis and cholecystectomy was reported by 9.5% and 3.6% of participants at baseline, respectively. After a total of 859 882 person-years of follow-up for women and 391 093 for men, incident liver cancer was detected in 160 women and 252 men. A positive association was observed between a history of cholelithiasis or cholecystectomy and liver cancer in men (aHR 1.46; 95% CI 1.02 to 2.07) and women (aHR 1.55; 95% CI 1.06 to 2.26). Similar results were observed for cholelithiasis only, but cholecystectomy did not reach statistical significance. There was no strong evidence for detection bias of liver cancer due to cholelithiasis or cholecystectomy. Conclusions Our study suggests that cholelithiasis and possibly cholecystectomy may increase the risk of liver cancer. C1 [Vogtmann, Emily; Li, Hong-Lan; Gao, Yu-Tang; Xiang, Yong-Bing] Shanghai Jiao Tong Univ, Shanghai Canc Inst, Renji Hosp, State Key Lab Oncogene & Related Genes,Sch Med, Shanghai 200032, Peoples R China. [Vogtmann, Emily; Li, Hong-Lan; Gao, Yu-Tang; Xiang, Yong-Bing] Shanghai Jiao Tong Univ, Shanghai Canc Inst, Renji Hosp, Dept Epidemiol,Sch Med, Shanghai 200032, Peoples R China. [Vogtmann, Emily; Shu, Xiao-Ou; Yang, Gong; Cai, Hui; Zheng, Wei] Vanderbilt Univ, Sch Med, Vanderbilt Ingram Canc Ctr, Div Epidemiol,Dept Med,Vanderbilt Epidemiol Ctr, Nashville, TN 37212 USA. [Vogtmann, Emily] Univ Alabama Birmingham, Sch Publ Hlth, Dept Epidemiol, Birmingham, AL 35294 USA. [Chow, Wong-Ho] Univ Texas MD Anderson Canc Ctr, Dept Epidemiol, Houston, TX 77030 USA. [Ji, Bu-Tian] NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. [Yu, Chang] Vanderbilt Univ, Sch Med, Dept Biostat, Nashville, TN 37212 USA. RP Xiang, YB (reprint author), Shanghai Jiao Tong Univ, Sch Med, Renji Hosp, Shanghai Canc Inst, 25,Lane 2200,Xie Tu Rd, Shanghai 200032, Peoples R China. EM ybxiang@shsci.org FU State Key Project Specialized for Infectious Diseases of China [2008ZX10002-015, 2012ZX10002008-002]; United States National Institutes of Health [R37 CA070867, R01 CA082729]; Fogarty International Clinical Research Scholars and Fellows Program at Vanderbilt University [R24 TW007988-5]; Cancer Prevention and Control Training Program at the University of Alabama at Birmingham - National Institutes of Health [5R25 CA047888] FX This work was supported by funds from the State Key Project Specialized for Infectious Diseases of China (No. 2008ZX10002-015 and 2012ZX10002008-002 to Y-BX); the United States National Institutes of Health (R37 CA070867 to WZ, and R01 CA082729 to X-OS); the Fogarty International Clinical Research Scholars and Fellows Program at Vanderbilt University (R24 TW007988-5 to EV and H-LL); and the Cancer Prevention and Control Training Program at the University of Alabama at Birmingham funded through the National Institutes of Health (5R25 CA047888 to EV). The funding organisations had no role in the design and conduct of the study; the collection, analysis and interpretation of the data; or the preparation, review or approval of the manuscript. NR 30 TC 1 Z9 1 U1 1 U2 5 PU BMJ PUBLISHING GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 0143-005X EI 1470-2738 J9 J EPIDEMIOL COMMUN H JI J. Epidemiol. Community Health PD JUN PY 2014 VL 68 IS 6 BP 565 EP 570 DI 10.1136/jech-2013-203503 PG 6 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA AG4AV UT WOS:000335362000013 PM 24574318 ER PT J AU Ito, T Li, XM Kurima, K Choi, BY Wangemann, P Griffith, AJ AF Ito, Taku Li, Xiangming Kurima, Kiyoto Choi, Byung Yoon Wangemann, Philine Griffith, Andrew J. TI Slc26a4-insufficiency causes fluctuating hearing loss and stria vascularis dysfunction SO NEUROBIOLOGY OF DISEASE LA English DT Article DE Conditional; Doxycycline; Endocochlear potential; Fluctuation; Hearing loss; Hypomorph; Inducible; SLC26A4; Stria vascularis; Transgenic; Vestibular aqueduct ID SYNDROME MOUSE MODEL; VESTIBULAR AQUEDUCT SYNDROME; GENOTYPE-PHENOTYPE CORRELATION; KCNJ10 PROTEIN EXPRESSION; BLOOD-BRAIN-BARRIER; K-CL COTRANSPORTER; OUTER HAIR-CELLS; PENDRED-SYNDROME; INNER-EAR; ENDOLYMPHATIC HYDROPS AB SLC26A4 mutations can cause a distinctive hearing loss phenotype with sudden drops and fluctuation inpatients. Existing Slc26a4 mutant mouse lines have a profound loss of hearing and vestibular function, with severe inner ear malformations that do not model this human phenotype. In this study, we generated.51c26a4-insufficient mice by manipulation of doxycycline administration to a transgenic mouse line in which all S1c26a4 expression was under the control of doxycycline. Doxycycline was administered from conception to embryonic day 17.5, and then it was discontinued. Auditory brainstem response thresholds showed significant fluctuation of hearing loss from 1 through 3 months of age. The endocochlear potential, which is required for inner ear sensory cell function, correlated with auditory brainstem response thresholds. We observed degeneration of stria vascularis intermediate cells, the cells that generate the endocochlear potential, but no other abnormalities within the cochlea. We conclude that fluctuations of hearing result from fluctuations of the endocochlear potential and stria vascularis dysfunction in S1c26a4-insufficient mouse ears. This model can now be used to test potential interventions to reduce or prevent sudden hearing loss or fluctuation in human patients. Our strategy to generate a hypomorphic mouse model utilizing the tet-on system will be applicable to other diseases in which a hypomorphic allele is needed to model the human phenotype. Published by Elsevier Inc. C1 [Ito, Taku; Kurima, Kiyoto; Griffith, Andrew J.] Natl Inst Deafness & Commun Disorders, Otolaryngol Branch, NIH, Bethesda, MD 20892 USA. [Li, Xiangming; Wangemann, Philine] Kansas State Univ, Dept Anat & Physiol, Manhattan, KS 66506 USA. [Choi, Byung Yoon] Natl Inst Deafness & Commun Disorders, Mol Genet Lab, NIH, Bethesda, MD 20892 USA. RP Griffith, AJ (reprint author), Natl Inst Deafness & Commun Disorders, Otolaryngol Branch, NIH, 35A Convent Dr,Room GF-103, Bethesda, MD 20892 USA. EM griffita@nidcd.nih.gov FU National Institutes of Health intramural research [DC-Z01-000039-16, DC-Z01-000060-12, NIH-R01-DC012151]; CVM-SMILE from Kansas State University; National Institutes of Health extramural fund [P20-RR017686] FX The authors thank Daniel Marcus and our NIDCD colleagues for helpful discussions, and Thomas Friedman and Tracy Fitzgerald for critical review of the manuscript. This work was supported by the National Institutes of Health intramural research funds DC-Z01-000039-16, DC-Z01-000060-12, NIH-R01-DC012151 and CVM-SMILE from Kansas State University, and the National Institutes of Health extramural fund P20-RR017686. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 70 TC 4 Z9 4 U1 1 U2 4 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0969-9961 EI 1095-953X J9 NEUROBIOL DIS JI Neurobiol. Dis. PD JUN PY 2014 VL 66 BP 53 EP 65 DI 10.1016/j.nbd.2014.02.002 PG 13 WC Neurosciences SC Neurosciences & Neurology GA AG0IG UT WOS:000335098600005 PM 24561068 ER PT J AU McCrindle, BW Zak, V Pemberton, VL Lambert, LM Vetter, VL Lai, WW Uzark, K Margossian, R Atz, AM Cook, A Newburger, JW AF McCrindle, Brian W. Zak, Victor Pemberton, Victoria L. Lambert, Linda M. Vetter, Victoria L. Lai, Wyman W. Uzark, Karen Margossian, Renee Atz, Andrew M. Cook, Amanda Newburger, Jane W. CA Pediatric Heart Network Investigat TI Functional health status in children and adolescents after Fontan: comparison of generic and disease-specific assessments SO CARDIOLOGY IN THE YOUNG LA English DT Article DE Fontan procedure; paediatrics; congenital; cardiac defects ID QUALITY-OF-LIFE; CONGENITAL CARDIAC-DISEASE; ACQUIRED HEART-DISEASE; PHYSICAL-ACTIVITY; VALIDATION; RESPONSIVENESS; RELIABILITY; INVENTORY; VALIDITY; PARENTS AB Purpose: The aim of this study was to compare associations between generic versus disease-specific functional health status assessments and patient and clinical characteristics for patients with severe congenital heart disease. Methods: This was a cross-sectional observational study involving 325 single ventricle patients, aged 10-18 years, after Fontan procedure. Enrolled patients underwent a medical history review, laboratory testing, and assessment of the functional health status by completion of the generic Child Report Child Health Questionnaire and the disease-specific Congenital Heart Adolescent and Teenage questionnaire. Correlated conceptually equivalent domains from both questionnaires were identified and their associations with patient and clinical variables were compared. Results: From the generic assessment, patients perceived marginally lower physical functioning (p = 0.05) but greater freedom from bodily pain compared with a normal population (p < 0.001). The equivalent physical functioning/limitations domain of the generic instrument, compared with the disease-specific instrument, had similar associations (higher multi-variable model R-2) with medical history variables (R-2 = 0.14 versus R-2 = 0.12, respectively) and stronger associations with exercise testing variables (R-2 = 0.22 versus R-2 = 0.06). Similarly, the corresponding freedom from bodily pain/symptoms domains from both questionnaires showed a greater association for the generic instrument with medical history variables (R-2 = 0.15 versus R-2 = 0.09, respectively) and non-cardiac conditions (R-2 = 0.13 versus R-2 = 0.06). The associations of each questionnaire with echocardiographic results, cardiac magnetic resonance imaging results, and serum brain natriuretic peptide levels were uniformly weak (R-2 range <0.01 to 0.04). Conclusions: Assessment of the physical functional health status using generic and disease-specific instruments yields few differences with regard to associations between conceptually similar domains and patient and clinical characteristics for adolescents after Fontan procedure. C1 [McCrindle, Brian W.] Univ Toronto, Hosp Sick Children, Toronto, ON M5G 1X8, Canada. [Zak, Victor] New England Res Inst, Watertown, MA 02172 USA. [Pemberton, Victoria L.] NHLBI, NIH, Bethesda, MD 20892 USA. [Lambert, Linda M.] Univ Utah, Primary Childrens Med Ctr, Salt Lake City, UT USA. [Vetter, Victoria L.] Childrens Hosp Philadelphia, Philadelphia, PA 19104 USA. [Lai, Wyman W.] Columbia Univ, Med Ctr, New York, NY USA. [Uzark, Karen] Cincinnati Childrens Hosp Med Ctr, Cincinnati, OH 45229 USA. [Margossian, Renee; Newburger, Jane W.] Childrens Hosp Boston, Boston, MA USA. [Atz, Andrew M.] Med Univ S Carolina, Charleston, SC 29425 USA. [Cook, Amanda] Wake Forest Univ, Baptist Med Ctr, Winston Salem, NC 27109 USA. RP McCrindle, BW (reprint author), Univ Toronto, Hosp Sick Children, 555 Univ Ave, Toronto, ON M5G 1X8, Canada. EM brian.mccrindle@sickkids.ca RI Hurwitz Koweek, lynne/N-1351-2015 OI Hurwitz Koweek, lynne/0000-0001-9990-3397 FU National Institutes of Health, National Heart, Lung, and Blood Institute [HL068269, HL068270, HL068279, HL068281, HL068285, HL068292, HL068290, HL068288] FX None of the authors have any financial disclosures to make. The study was supported by U01 grants from the National Institutes of Health, National Heart, Lung, and Blood Institute (HL068269, HL068270, HL068279, HL068281, HL068285, HL068292, HL068290, HL068288). The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Heart, Lung and Blood Institute or the National Institutes of Health. NR 35 TC 3 Z9 3 U1 0 U2 8 PU CAMBRIDGE UNIV PRESS PI CAMBRIDGE PA EDINBURGH BLDG, SHAFTESBURY RD, CB2 8RU CAMBRIDGE, ENGLAND SN 1047-9511 EI 1467-1107 J9 CARDIOL YOUNG JI Cardiol. Young PD JUN PY 2014 VL 24 IS 3 BP 469 EP 477 DI 10.1017/S1047951113000632 PG 9 WC Cardiac & Cardiovascular Systems; Pediatrics SC Cardiovascular System & Cardiology; Pediatrics GA AF7GX UT WOS:000334883700014 PM 23746330 ER PT J AU Raft, S Andrade, LR Shao, DM Akiyama, H Henkemeyer, M Wu, DK AF Raft, Steven Andrade, Leonardo R. Shao, Dongmei Akiyama, Haruhiko Henkemeyer, Mark Wu, Doris K. TI Ephrin-B2 governs morphogenesis of endolymphatic sac and duct epithelia in the mouse inner ear SO DEVELOPMENTAL BIOLOGY LA English DT Article DE Ephrin-B2; EphB2; Eph-ephrin; Foxi1; Notch; Pendrin; Slc26a4; Proton-translocating ATPase; DIx5; Gbx2; Signaling; Morphogenesis; Proliferation; Growth; Mouse; Embryo; Cre-mediated gene inactivation; Inner ear; Otocyst; Vestibular; Deafness; Endolymph; Otoconia; Fluid homeostasis; Endolymphatic sac; Endolymphatic duct ID RENAL TUBULAR-ACIDOSIS; TRANSCRIPTION FACTOR FOXI1; VESTIBULAR AQUEDUCT; CELL-PROLIFERATION; PENDRED-SYNDROME; TARGETED DISRUPTION; DEFICIENT MICE; HEARING-LOSS; DEAFNESS; DEFECTS AB Control over ionic composition and volume of the inner ear luminal fluid endolymph is essential for normal hearing and balance. Mice deficient in either the EphB2 receptor tyrosine kinase or the cognate transmembrane ligand ephrin-B2 (Efnb2) exhibit background strain-specific vestibular-behavioral dysfunction and signs of abnormal endolymph homeostasis. Using various loss-of-function mouse models, we found that Efnb2 is required for growth and morphogenesis of the embryonic endolymphatic epithelium, a precursor of the endolymphatic sac (ES) and duct (ED), which mediate endolymph homeostasis. Conditional inactivation of Efnb2 in early-stage embryonic ear tissues disrupted cell proliferation, cell survival, and epithelial folding at the origin of the endolymphatic epithelium. This correlated with apparent absence of an ED, mis-localization of ES ion transport cells relative to inner ear sensory organs, dysplasia of the endolymph fluid space, and abnormally formed otoconia (extracellular calcite-protein composites) at later stages of embryonic development. A comparison of Efnb2 and Notch signaling-deficient mutant phenotypes indicated that these two signaling systems have distinct and non-overlapping roles in ES/ED development. Homozygous deletion of the Efnb2 C-terminus caused abnormalities similar to those found in the conditional Efnb2 null homozygote. Analyses of fetal Efnb2 C-terminus deletion heterozygotes found mis-localized ES ion transport cells only in the genetic background exhibiting vestibular dysfunction. We propose that developmental dysplasias described here are a gene dose-sensitive cause of the vestibular dysfunction observed in EphB-Efnb2 signaling-deficient mice. Published by Elsevier Inc. C1 [Raft, Steven; Wu, Doris K.] Natl Inst Deafness & Other Commun Disorders, Sect Sensory Cell Regenerat & Dev, NIH, Bethesda, MD 20892 USA. [Andrade, Leonardo R.] Univ Fed Rio de Janeiro, CCS, Inst Biomed Sci, Lab Biomineralizat, BR-21941902 Rio De Janeiro, Brazil. [Shao, Dongmei] Univ Texas SW Med Ctr Dallas, Dept Otolaryngol, Dallas, TX 75390 USA. [Akiyama, Haruhiko] Gifu Univ, Dept Orthoped, Gifu 5011194, Japan. [Henkemeyer, Mark] Univ Texas SW Med Ctr Dallas, Dept Dev Biol, Dallas, TX 75390 USA. RP Raft, S (reprint author), Natl Inst Deafness & Other Commun Disorders, Sect Sensory Cell Regenerat & Dev, NIH, Bethesda, MD 20892 USA. EM rafts@nidcd.nih.gov; wud@nidcd.nih.gov RI Andrade, Leonardo/C-9554-2011 OI Andrade, Leonardo/0000-0002-0004-5677 FU Intramural NIH HHS [Z99 DC999999, ZIA DC000021-20]; NIMH NIH HHS [R01 MH066332] NR 79 TC 5 Z9 5 U1 0 U2 8 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0012-1606 EI 1095-564X J9 DEV BIOL JI Dev. Biol. PD JUN 1 PY 2014 VL 390 IS 1 BP 51 EP 67 DI 10.1016/j.ydbio.2014.02.019 PG 17 WC Developmental Biology SC Developmental Biology GA AF2UO UT WOS:000334568200005 PM 24583262 ER PT J AU Mueller, GA Ankney, JA Glesner, J Khurana, T Edwards, LL Pedersen, LC Perera, L Slater, JE Pomes, A London, RE AF Mueller, Geoffrey A. Ankney, John A. Glesner, Jill Khurana, Taruna Edwards, Lori L. Pedersen, Lars C. Perera, Lalith Slater, Jay E. Pomes, Anna London, Robert E. TI Characterization of an anti-Bla g 1 scFv: Epitope mapping and cross-reactivity SO MOLECULAR IMMUNOLOGY LA English DT Article DE Allergen; Structure; Bla g 1; scFv; Cockroach; Epitope ID COCKROACH ALLERGEN BLA-G-2; INNER-CITY CHILDREN; MONOCLONAL-ANTIBODY; AMERICAN COCKROACH; HYDROGEN-EXCHANGE; MOLECULAR-CLONING; CRYSTAL-STRUCTURE; EXPOSURE; BINDING; IGE AB Bla g 1 is a major allergen from Blatella germanica and one of the primary allergens used to assess cockroach allergen exposure. The epitope of an anti-Bla g 1 scEv was mapped in order to better understand cross reactivity with other group 1 cockroach allergens and patient IgE epitopes. X-ray crystallography was used to determine the structure of the scFv. The scEv epitope on Bla g 1 was located by alanine scanning sitedirected mutagenesis and ELISA. Twenty-six rBla g 1-GST alanine mutants were evaluated for variations in binding to the scFv compared to the wild type allergen. Six mutants showed a significant difference in scFv binding affinity. These mutations clustered to form a discontinuous epitope mainly comprising two helices of Bla g 1. The allergen-scFv complex was modeled based on the results, and the epitope region was found to have low sequence similarity with Per a 1, especially among the residues identified as functionally important for the scFy binding to Bla g I. Indeed, the scEv failed to bind Per a 1 in American cockroach extract. The scEv was unable to inhibit the binding of IgE antibodies from a highly cockroach allergic patient to Bla g 1. Based on the surface area of Bla g 1 occluded by the scFv, putative regions of patient IgE-Bla g 1 interactions can be inferred. This scFy could be best utilized as a capture antibody in an IgE detection ELISA, or to differentiate Bla g 1 from Per a 1 in environmental exposure assays. Published by Elsevier Ltd. C1 [Mueller, Geoffrey A.; Ankney, John A.; Edwards, Lori L.; Pedersen, Lars C.; Perera, Lalith; London, Robert E.] NIEHS, NIH, Res Triangle Pk, NC 27709 USA. [Khurana, Taruna; Slater, Jay E.] US FDA, Bethesda, MD 20892 USA. [Glesner, Jill; Pomes, Anna] Indoor Biotechnol Inc, Charlottesville, VA 22903 USA. RP Mueller, GA (reprint author), NIEHS, NIH, POB 12233, Res Triangle Pk, NC 27709 USA. EM mueller3@niehs.nih.gov OI Pomes, Anna/0000-0002-8729-1829 FU Intramural Research Program of the National Institute of Environmental Health Sciences, National Institutes of Health [Z01-ES102885-01, ZIA-ES102645]; National Institute of Allergy and Infectious Diseases of the National Institutes of Health [R01A1077653]; U. S. Department of Energy, Office of Science, Office of Basic Energy Sciences [W-31-109-Eng-38] FX This research was supported in part by Research Project Number Z01-ES102885-01 to REL, and ZIA-ES102645 to LCP in the Intramural Research Program of the National Institute of Environmental Health Sciences, National Institutes of Health. Research reported in this publication was supported in part by the National Institute of Allergy and Infectious Diseases of the National Institutes of Health under Award Number R01A1077653 (PI: AP). The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. Use of the Advanced Photon Source was supported by the U. S. Department of Energy, Office of Science, Office of Basic Energy Sciences, under Contract No. W-31-109-Eng-38. The authors thank Traci Hall and Andrea Moon for a critical reading of the manuscript. NR 37 TC 1 Z9 1 U1 0 U2 17 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0161-5890 J9 MOL IMMUNOL JI Mol. Immunol. PD JUN PY 2014 VL 59 IS 2 BP 200 EP 207 DI 10.1016/j.molimm.2014.02.003 PG 8 WC Biochemistry & Molecular Biology; Immunology SC Biochemistry & Molecular Biology; Immunology GA AF8TP UT WOS:000334988800011 PM 24667070 ER PT J AU Yedjou, CG Saeed, MA Hossain, MA Dorsey, W Yu, HT Tchounwou, PB AF Yedjou, Clement G. Saeed, Musabbir A. Hossain, Md. Alamgir Dorsey, Waneene Yu, Hongtao Tchounwou, Paul B. TI Basic apoptotic and necrotic cell death in human liver carcinoma (HepG(2)) cells induced by synthetic azamacrocycle SO ENVIRONMENTAL TOXICOLOGY LA English DT Article DE HepG2 cells; cytotoxicity; azamacrocycle; necrosis; apoptosis ID TRANSCRIPTIONAL ACTIVATION; STRESS GENES; CANCER CELLS; NECROSIS; EXPRESSION; RECEPTORS; COMPLEXES; ANALOGS; ANION AB Treatment of diseases with synthetic materials has been an aspiration of mankind since the dawn of human development. In this research, three complex compounds of azamacrocycle (TD1, TD2, and TD3) were synthesized, and experiments were conducted to determine whether their toxicity to human liver carcinoma (HepG(2)) cells is associated with apoptotic and/or necrotic cell death. Cell survival was determined by MTT assay. Apoptosis and necrosis were measured by annexin V FITC/PI assay using the flow cytometry and by propidium iodide (PI) assay using the cellometer vision. HepG(2) cells were treated with different concentrations of azamacrocycles for 48 h. Results from MTT assay indicated that all the three azamacrocycles significantly (p < 0.05) reduce cell viability in a dose-dependent manner, showing 48 h-LD50 values of about 37.97, 33.60, and 19.29 mu M, for TD3, TD1 and TD2, respectively. Among the three compounds tested, TD2 showed the most pronounced cytotoxic activity against HepG(2) cells, being about twofold more potent than TD3. The order of toxicity was TD2 > TD1 > TD3. Because TD2 exerted the most cytotoxic activity against HepG(2) cells, it was used in the subsequent apoptosis and necrosis-related experiments. The flow cytometry assessment showed a strong dose-response relationship with regard to TD2 exposure and annexin V/PI positive cells. PI assay data indicated that TD2 exposure increased the proportion of fluorescence positive cells. Overall, our results indicate that azamacrocycle toxicity to HepG(2) cells is associated with apoptotic and necrotic cell death resulting from phosphatidylserine externalization and loss of membrane integrity. (c) 2012 Wiley Periodicals, Inc. Environ Toxicol 29: 605-611, 2014. C1 [Yedjou, Clement G.; Dorsey, Waneene; Tchounwou, Paul B.] Jackson State Univ, NIH RCMI Ctr Environm Hlth, Cell & Toxicogen Res Lab, Jackson, MS 39217 USA. [Saeed, Musabbir A.; Hossain, Md. Alamgir; Yu, Hongtao] Jackson State Univ, Dept Chem & Biochem, Jackson, MS 39217 USA. RP Tchounwou, PB (reprint author), Jackson State Univ, NIH RCMI Ctr Environm Hlth, Cell & Toxicogen Res Lab, 1400 Lynch St,POB 18540, Jackson, MS 39217 USA. EM paul.b.tchounwou@jsums.edu FU National Institutes of Health (RCMI-Center for Environmental Health at Jackson State University) [5G12RR013459-14]; National Science Foundation [CHE-0821357] FX Contract grant sponsor: National Institutes of Health (RCMI-Center for Environmental Health at Jackson State University).; Contract grant number: 5G12RR013459-14.; Contract grant sponsor: National Science Foundation.; Contract grant number: CHE-0821357. NR 39 TC 4 Z9 4 U1 0 U2 19 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1520-4081 EI 1522-7278 J9 ENVIRON TOXICOL JI Environ. Toxicol. PD JUN PY 2014 VL 29 IS 6 BP 605 EP 611 DI 10.1002/tox.21786 PG 7 WC Environmental Sciences; Toxicology; Water Resources SC Environmental Sciences & Ecology; Toxicology; Water Resources GA AE9BS UT WOS:000334299500001 PM 22644747 ER PT J AU Kim, GY Gabrea, A Demchenko, YN Bergsagel, L Roschke, AV Kuehl, WM AF Kim, Gina Y. Gabrea, Ana Demchenko, Yulia N. Bergsagel, Leif Roschke, Anna V. Kuehl, W. Michael TI Complex IGH rearrangements in multiple myeloma: Frequent detection discrepancies among three different probe sets SO GENES CHROMOSOMES & CANCER LA English DT Article ID TRANSLOCATIONS; ABNORMALITIES; IMMUNOGLOBULIN; PROGRESSION; 14Q32; CELL AB Primary IGH translocations involving seven recurrent partner loci and oncogenes are present in about 40% of multiple myeloma tumors. Secondary IGH rearrangements, which occur in a smaller fraction of tumors, usually are complex structures, including insertions or translocations that can involve three chromosomes, and often with involvement of MYC. The main approach to detect IGH rearrangements is interphase-but sometimes metaphase-FISH strategies that use a telomeric variable region probe and a centromeric constant region/ E alpha enhancer or 3 ' flanking probe to detect a separation of these two probes, or a fusion of these probes with probes located at nonrandom partner sites in the genome. We analyzed 18 myeloma cell lines for detection discrepancies among Vysis, Cytocell, and in-house IGH probe sets that hybridize with differing sequences in the IGH locus. There were no detection discrepancies for the three telomeric IGH probes, or for unrearranged IGH loci or primary IGH translocations using the centromeric IGH probes. However, the majority of complex IGH rearrangements had detection discrepancies among the three centromeric IGH probes. (c) 2014 Wiley Periodicals, Inc. C1 [Kim, Gina Y.; Gabrea, Ana; Demchenko, Yulia N.; Roschke, Anna V.; Kuehl, W. Michael] NCI, Genet Branch, Bethesda, MD 20892 USA. [Bergsagel, Leif] Mayo Clin Arizona, Ctr Comprehens Canc, Scottsdale, AZ USA. RP Kuehl, WM (reprint author), NCI, Genet Branch, Ctr Canc Res, NIH, 37 Convent Dr,Bldg 37,Room 6002C, Bethesda, MD 20892 USA. EM kuehlw@helix.nih.gov FU Intramural Research Program of the National Institute of Health, National Cancer Institute, Center for Cancer Research FX Supported by: The Intramural Research Program of the National Institute of Health, National Cancer Institute, Center for Cancer Research. NR 18 TC 1 Z9 1 U1 0 U2 4 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1045-2257 EI 1098-2264 J9 GENE CHROMOSOME CANC JI Gene Chromosomes Cancer PD JUN PY 2014 VL 53 IS 6 BP 467 EP 474 DI 10.1002/gcc.22158 PG 8 WC Oncology; Genetics & Heredity SC Oncology; Genetics & Heredity GA AE2LE UT WOS:000333803600003 PM 24585545 ER PT J AU Simpson, MS Demner-Fushman, D Antani, SK Thoma, GR AF Simpson, Matthew S. Demner-Fushman, Dina Antani, Sameer K. Thoma, George R. TI Multimodal biomedical image indexing and retrieval using descriptive text and global feature mapping SO INFORMATION RETRIEVAL LA English DT Article DE Multimodal image retrieval; Image indexing; Clustering ID BAYES POINT MACHINES; ANNOTATION; SEARCH; QUANTIZATION; DATABASES; PICTURES; FUSION; SCALE; QUERY AB The images found within biomedical articles are sources of essential information useful for a variety of tasks. Due to the rapid growth of biomedical knowledge, image retrieval systems are increasingly becoming necessary tools for quickly accessing the most relevant images from the literature for a given information need. Unfortunately, article text can be a poor substitute for image content, limiting the effectiveness of existing text-based retrieval methods. Additionally, the use of visual similarity by content-based retrieval methods as the sole indicator of image relevance is problematic since the importance of an image can depend on its context rather than its appearance. For biomedical image retrieval, multimodal approaches are often desirable. We describe in this work a practical multimodal solution for indexing and retrieving the images contained in biomedical articles. Recognizing the importance of text in determining image relevance, our method combines a predominately text-based image representation with a limited amount of visual information, in the form of quantized content-based visual features, through a process called global feature mapping. The resulting multimodal image surrogates are easily indexed and searched using existing text-based retrieval systems. Our experimental results demonstrate that our multimodal strategy significantly improves upon the retrieval accuracy of existing approaches. In addition, unlike many retrieval methods that utilize content-based visual features, the response time of our approach is negligible, making it suitable for use with large collections. C1 [Simpson, Matthew S.; Demner-Fushman, Dina; Antani, Sameer K.; Thoma, George R.] NIH, Lister Hill Natl Ctr Biomed Commun, US Natl Lib Med, Bethesda, MD 20892 USA. RP Simpson, MS (reprint author), NIH, Lister Hill Natl Ctr Biomed Commun, US Natl Lib Med, Bldg 10, Bethesda, MD 20892 USA. EM simpsonmatt@mail.nih.gov; ddemner@mail.nih.gov; santani@mail.nih.gov; gthoma@mail.nih.gov OI Antani, Sameer/0000-0002-0040-1387 FU U.S. National Library of Medicine, National Institutes of Health FX The authors would like to thank Dr. Md. Mahmudur Rahman and Srinivas Phadnis for extracting and preparing the content-based and text-based features of the images used in this work. This work is supported by the intramural research program of the U.S. National Library of Medicine, National Institutes of Health, and by an appointment to the NLM Research Participation Program administered by the Oak Ridge Institute for Science and Education. NR 86 TC 2 Z9 2 U1 0 U2 10 PU SPRINGER PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 1386-4564 EI 1573-7659 J9 INFORM RETRIEVAL JI Inf. Retr. PD JUN PY 2014 VL 17 IS 3 BP 229 EP 264 DI 10.1007/s10791-013-9235-2 PG 36 WC Computer Science, Information Systems SC Computer Science GA AF1SQ UT WOS:000334494200002 ER PT J AU Gattass, R Galkin, TW Desimone, R Ungerleider, LG AF Gattass, Ricardo Galkin, Thelma W. Desimone, Robert Ungerleider, Leslie G. TI Subcortical Connections of Area V4 in the Macaque SO JOURNAL OF COMPARATIVE NEUROLOGY LA English DT Article DE pulvinar; claustrum; caudate; putamen; superior colliculus; amygdala ID LATERAL GENICULATE-NUCLEUS; MONKEY SUPERIOR COLLICULUS; INFERIOR PULVINAR COMPLEX; VISUAL-SPATIAL ATTENTION; CALCIUM-BINDING PROTEINS; SUB-CORTICAL STRUCTURES; BEHAVING RHESUS-MONKEY; NEW-WORLD MONKEY; STRIATE CORTEX; MACACA-MULATTA AB Area V4 has numerous, topographically organized connections with multiple cortical areas, some of which are important for spatially organized visual processing, and others which seem important for spatial attention. Although the topographic organization of V4's connections with other cortical areas has been established, the detailed topography of its connections with subcortical areas is unclear. We therefore injected retrograde and anterograde tracers in different topographical regions of V4 in nine macaques to determine the organization of its subcortical connections. The injection sites included representations ranging from the fovea to far peripheral eccentricities in both the upper and lower visual fields. The topographically organized connections of V4 included bidirectional connections with four subdivisions of the pulvinar, two subdivisions of the claustrum, and the interlaminar portions of the lateral geniculate nucleus, and efferent projections to the superficial and intermediate layers of the superior colliculus, the thalamic reticular nucleus, and the caudate nucleus. All of these structures have a possible role in spatial attention. The nontopographic, or converging, connections included bidirectional connections with the lateral nucleus of the amygdala, afferent inputs from the dorsal raphe, median raphe, locus coeruleus, ventral tegmentum and nucleus basalis of Meynert, and efferent projections to the putamen. Any role of these structures in attention may be less spatially specific. J. Comp. Neurol. 522:1941-1965, 2014. (c) 2013 Wiley Periodicals, Inc. C1 [Gattass, Ricardo] Univ Fed Rio de Janeiro, Inst Biofis Carlos Chagas Filho, Lab Cognit Physiol, BR-21941900 Rio de Janeiro, RJ, Brazil. [Galkin, Thelma W.; Ungerleider, Leslie G.] NIMH, Lab Brain & Cognit, NIH, Bethesda, MD 20892 USA. [Desimone, Robert] NIMH, Neuropsychol Lab, NIH, Bethesda, MD 20892 USA. [Desimone, Robert] MIT, McGovern Inst, Cambridge, MA 02139 USA. RP Ungerleider, LG (reprint author), Lab Brain & Cognit, NIMH Bldg 10,Room 4C104,10 Ctr Dr, Bethesda, MD 20892 USA. EM ungerlel@mail.nih.gov FU NIMH Intramural Research Program; NEI, NIH [RO1EY017292] FX Grant sponsor: NIMH Intramural Research Program; Grant sponsor: NEI, NIH; Grant number: RO1EY017292 (to R.D.). NR 136 TC 10 Z9 10 U1 3 U2 17 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0021-9967 EI 1096-9861 J9 J COMP NEUROL JI J. Comp. Neurol. PD JUN 1 PY 2014 VL 522 IS 8 BP 1941 EP 1965 DI 10.1002/cne.23513 PG 25 WC Neurosciences; Zoology SC Neurosciences & Neurology; Zoology GA AD9RW UT WOS:000333603200015 PM 24288173 ER PT J AU Henning, T Butler, K Mitchell, J Ellis, S Deyounks, F Farshy, C Phillips, C Papp, J Patton, D Caldwell, H Sturdevant, G McNicholl, J Kersh, E AF Henning, Tara Butler, Katherine Mitchell, James Ellis, Shanon Deyounks, Frank Farshy, Carol Phillips, Christi Papp, John Patton, Dorothy Caldwell, Harlan Sturdevant, Gail McNicholl, Janet Kersh, Ellen TI Development of a rectal sexually transmitted infection - HIV coinfection model utilizing Chlamydia trachomatis and SHIVSF162p3 SO JOURNAL OF MEDICAL PRIMATOLOGY LA English DT Article DE men who have sex with men; STD ID HUMAN-IMMUNODEFICIENCY-VIRUS; NEISSERIA-GONORRHOEAE; NONHUMAN-PRIMATES; MACAQUE MODEL; GENITAL-TRACT; TRANSMISSION; SEX; MEN; TENOFOVIR; SYSTEM AB BackgroundRectal sexually transmitted infections (STIs) may increase HIV susceptibility in men who have sex with men (MSM), and Chlamydia trachomatis is prevalent among HIV-positive MSM. To study STIs and HIV infection in MSM, we first evaluated whether cynomolgus macaques can sustain both C.trachomatis and SHIVSF162p3 infections(.) MethodsFour SHIVSF162p3-positive male cynomolgus macaques were used (n=3 rectally inoculated with 10(6) IFU; n=1 control). Systemic and rectal SHIV RNA levels and cytokines were measured by real-time PCR and Luminex assays, respectively. ResultsMacaques were successfully Chlamydia infected. Rectal SHIV shedding (P=0.02 (2)) and levels of G-CSF, IL-1ra, IL-6, IL-8, IFN-, and TNF- (P0.01, Mann-Whitney) in rectal secretions increased following infection. ConclusionsThese pilot data successfully demonstrate rectal C.trachomatis-SHIV coinfection in cynomolgus macaques and suggest the feasibility of a rectal C.trachomatis model for SHIV susceptibility and biomedical prevention studies in the context of rectal STIs. C1 [Henning, Tara; Butler, Katherine; Mitchell, James; Ellis, Shanon; Deyounks, Frank; McNicholl, Janet; Kersh, Ellen] Ctr Dis Control & Prevent, Div HIV AIDS Prevent, Atlanta, GA 30333 USA. [Farshy, Carol; Phillips, Christi; Papp, John] Ctr Dis Control & Prevent, Div STD Prevent, Atlanta, GA 30333 USA. [Patton, Dorothy] Univ Washington, Dept Obstet & Gynecol, Seattle, WA 98195 USA. [Caldwell, Harlan; Sturdevant, Gail] NIAID, Intracellular Parasites Lab, Rocky Mt Labs, NIH, Hamilton, MT USA. RP Kersh, E (reprint author), Ctr Dis Control & Prevent, Div HIV AIDS Prevent, 1600 Clifton Rd NE,MS A-25, Atlanta, GA 30333 USA. EM ekersh@cdc.gov FU CDC [Y1-A1-0681-02]; NIH [Y1-A1-0681-02] FX The authors thank Dr. John Brooks and Dr. Pragna Patel for advisement on rectal pathogens. The authors thank Patty Guenthner for her assistance with macaques' SHIV infection data from the previous titration study. This work was funded by CDC and an interagency agreement (Y1-A1-0681-02) between CDC and NIH. NR 27 TC 3 Z9 3 U1 0 U2 4 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0047-2565 EI 1600-0684 J9 J MED PRIMATOL JI J. Med. Primatol. PD JUN PY 2014 VL 43 IS 3 BP 135 EP 143 DI 10.1111/jmp.12103 PG 9 WC Veterinary Sciences; Zoology SC Veterinary Sciences; Zoology GA AF2EF UT WOS:000334524700001 PM 24460742 ER PT J AU Vaughan, KL Szarowicz, MD Herbert, RL Mattison, JA AF Vaughan, Kelli L. Szarowicz, Mark D. Herbert, Richard L. Mattison, Julie A. TI Comparison of anesthesia protocols for intravenous glucose tolerance testing in rhesus monkeys SO JOURNAL OF MEDICAL PRIMATOLOGY LA English DT Article DE glucose regulation; IVGTT; non-human primate; pharmacology; rhesus macaque ID MACACA-MULATTA; MEDETOMIDINE; MACAQUES; KETAMINE; CATS; RATS AB BackgroundDrugs commonly used to sedate non-human primates for physiological sample collection can affect the metabolic system and alter rates of glucose metabolism. This study was designed to compare the physiological and metabolic effects of ketamine/diazepam, telazol, and ketamine/dexmedetomidine. MethodsSeven female rhesus monkeys underwent intravenous glucose tolerance testing under each of three anesthesia conditions. Blood glucose, insulin, physiological parameters, and sedation characteristics were measured and recorded. ResultsGlucose and insulin values were both significantly impacted by ketamine/dexmedetomidine sedation while remaining consistent during ketamine and telazol sedation. Heart rate was also significantly lowered during ketamine/dexmedetomidine anesthesia. Though, ketamine/dexmedetomidine resulted in a longer time between induction of anesthesia and need for a supplemental dose of anesthesia drug. ConclusionsTelazol and ketamine have minimal cardiorespiratory and metabolic effects compared to ketamine/dexmedetomidine. Although practicably interchangeable, telazol appears to be the most efficient for intravenous glucose tolerance testings with non-human primates. C1 [Vaughan, Kelli L.; Szarowicz, Mark D.; Mattison, Julie A.] NIA, Translat Gerontol Branch, Intramural Res Program, NIH, Dickerson, MD 20842 USA. [Vaughan, Kelli L.; Szarowicz, Mark D.] SoBran Inc, Burtonsville, MD USA. [Herbert, Richard L.] NIAID, NIH, Anim Ctr, Dickerson, MD USA. RP Vaughan, KL (reprint author), NIA, Translat Gerontol Branch, Intramural Res Program, NIH, 16701 Elmer Sch Rd,Bldg 103, Dickerson, MD 20842 USA. EM kelli.vaughan@nih.gov OI Vaughan, Kelli/0000-0001-5274-582X FU Intramural Research Program, National Institute on Aging, NIH FX The authors would like to thank Joe Travis, Rob Young, and Ed Tilmont for their technical support. This project was supported entirely by the Intramural Research Program, National Institute on Aging, NIH. NR 15 TC 3 Z9 3 U1 0 U2 9 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0047-2565 EI 1600-0684 J9 J MED PRIMATOL JI J. Med. Primatol. PD JUN PY 2014 VL 43 IS 3 BP 162 EP 168 DI 10.1111/jmp.12104 PG 7 WC Veterinary Sciences; Zoology SC Veterinary Sciences; Zoology GA AF2EF UT WOS:000334524700004 PM 24697511 ER PT J AU Canugovi, C Shamanna, RA Croteau, DL Bohr, VA AF Canugovi, Chandrika Shamanna, Raghavendra A. Croteau, Deborah L. Bohr, Vilhelm A. TI Base excision DNA repair levels in mitochondrial lysates of Alzheimer's disease SO NEUROBIOLOGY OF AGING LA English DT Article DE Base excision repair; 5-Hydroxyuracil; Ligation; Alzheimer's disease; Mitochondria ID INCREASED OXIDATIVE DAMAGE; MILD COGNITIVE IMPAIRMENT; CYTOCHROME-C-OXIDASE; AMYLOID-BETA; LIGASE-III; BRAIN; NUCLEAR; DELETIONS; DYSFUNCTION; MORPHOLOGY AB Alzheimer's disease (AD) is a senile dementia with increased incidence in older subjects (age > 65 years). One of the earliest markers of AD is oxidative DNA damage. Recently, it has been reported that preclinical AD patient brains show elevated levels of oxidative damage in both nuclear and mitochondrial nucleic acids. Moreover, different oxidative lesions in mitochondrial DNA are between 5- and 10-fold higher than in nuclear DNA in both control and AD postmortem brains. We previously showed that there is a significant loss of base excision repair (BER) components in whole tissue extracts of AD and mild cognitive impairment subjects relative to matched control subjects. However, comprehensive analysis of specific steps in BER levels in mitochondrial extracts of AD patient brains is not available. In this study, we mainly investigated various components of BER in mitochondrial extracts of AD and matched control postmortem brain samples. We found that the 5-hydroxyuracil incision and ligase activities are significantly lower in AD brains, whereas the uracil incision, abasic site cleavage, and deoxyribonucleotide triphosphate incorporation activities are normal in these samples. Published by Elsevier Inc. C1 [Canugovi, Chandrika; Shamanna, Raghavendra A.; Croteau, Deborah L.; Bohr, Vilhelm A.] Natl Inst Aging, Lab Mol Gerontol, Baltimore, MD 21224 USA. RP Bohr, VA (reprint author), Natl Inst Aging, Lab Mol Gerontol, 251 Bayview Blvd, Baltimore, MD 21224 USA. EM vbohr@nih.gov FU Intramural Research Program of the National Institutes of Health and National Institute on Aging FX This research was supported entirely by the Intramural Research Program of the National Institutes of Health and National Institute on Aging. We would like to thank Harvard Brain Bank for the human postmortem brain samples used in this study. Additionally, we would like to thank Huiming Lu and Somnath Ghosh for critically reading the manuscript. NR 35 TC 18 Z9 18 U1 1 U2 18 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0197-4580 EI 1558-1497 J9 NEUROBIOL AGING JI Neurobiol. Aging PD JUN PY 2014 VL 35 IS 6 BP 1293 EP 1300 DI 10.1016/j.neurobiolaging.2014.01.004 PG 8 WC Geriatrics & Gerontology; Neurosciences SC Geriatrics & Gerontology; Neurosciences & Neurology GA AE4RO UT WOS:000333970800009 PM 24485507 ER PT J AU Benitez, BA Jin, SC Guerreiro, R Graham, R Lord, J Harold, D Sims, R Lambert, JC Gibbs, JR Bras, J Sassi, C Harari, O Bertelsen, S Lupton, MK Powell, J Bellenguez, C Brown, K Medway, C Haddick, PCG van der Brug, MP Bhangale, T Ortmann, W Behrens, T Mayeux, R Pericak-Vance, MA Farrer, LA Schellenberg, GD Haines, JL Turton, J Braae, A Barber, I Fagan, AM Holtzman, DM Morris, JC Williams, J Kauwe, JSK Amouyel, P Morgan, K Singleton, A Hardy, J Goate, AM Cruchaga, C AF Benitez, Bruno A. Jin, Sheng Chih Guerreiro, Rita Graham, Rob Lord, Jenny Harold, Denise Sims, Rebecca Lambert, Jean-Charles Gibbs, J. Raphael Bras, Jose Sassi, Celeste Harari, Oscar Bertelsen, Sarah Lupton, Michelle K. Powell, John Bellenguez, Celine Brown, Kristelle Medway, Christopher Haddick, Patrick C. G. van der Brug, Marcel P. Bhangale, Tushar Ortmann, Ward Behrens, Tim Mayeux, Richard Pericak-Vance, Margaret A. Farrer, Lindsay A. Schellenberg, Gerard D. Haines, Jonathan L. Turton, Jim Braae, Anne Barber, Imelda Fagan, Anne M. Holtzman, David M. Morris, John C. Williams, Julie Kauwe, John S. K. Amouyel, Philippe Morgan, Kevin Singleton, Andy Hardy, John Goate, Alison M. Cruchaga, Carlos CA 3C Study Grp EADI Consortium ADGC ADNI GERAD Consortium TI Missense variant in TREML2 protects against Alzheimer's disease SO NEUROBIOLOGY OF AGING LA English DT Article DE TREM2; Genome-wide association studies; Conditional analysis; Endophenotype; Gene; Alzheimer's disease; Association ID ASSOCIATION AB TREM and TREM-like receptors are a structurally similar protein family encoded by genes clustered on chromosome 6p21.11. Recent studies have identified a rare coding variant (p. R47H) in TREM2 that confers a high risk for Alzheimer's disease (AD). In addition, common single nucleotide polymorphisms in this genomic region are associated with cerebrospinal fluid biomarkers for AD and a common intergenic variant found near the TREML2 gene has been identified to be protective for AD. However, little is known about the functional variant underlying the latter association or its relationship with the p. R47H. Here, we report comprehensive analyses using whole-exome sequencing data, cerebrospinal fluid biomarker analyses, meta-analyses (16,254 cases and 20,052 controls) and cell-based functional studies to support the role of the TREML2 coding missense variant p. S144G (rs3747742) as a potential driver of the metaanalysis AD-associated genome-wide association studies signal. Additionally, we demonstrate that the protective role of TREML2 in AD is independent of the role of TREM2 gene as a risk factor for AD. (C) 2014 Elsevier Inc. All rights reserved. C1 [Benitez, Bruno A.; Jin, Sheng Chih; Harari, Oscar; Bertelsen, Sarah; Goate, Alison M.; Cruchaga, Carlos] Washington Univ, Sch Med, Dept Psychiat, St Louis, MO 63110 USA. [Fagan, Anne M.; Holtzman, David M.; Morris, John C.; Goate, Alison M.] Washington Univ, Sch Med, Dept Neurol, St Louis, MO 63110 USA. [Morris, John C.] Washington Univ, Sch Med, Dept Pathol & Immunol, St Louis, MO 63110 USA. [Goate, Alison M.] Washington Univ, Sch Med, Dept Genet, St Louis, MO 63110 USA. [Holtzman, David M.; Morris, John C.] Washington Univ, Sch Med, Dept Dev Biol, St Louis, MO 63110 USA. [Fagan, Anne M.; Holtzman, David M.; Morris, John C.; Goate, Alison M.] Washington Univ, Sch Med, Knight Alzheimers Dis Res Ctr, St Louis, MO 63110 USA. [Fagan, Anne M.; Holtzman, David M.; Morris, John C.; Goate, Alison M.; Cruchaga, Carlos] Washington Univ, Sch Med, Hope Ctr Neurol Disorders, St Louis, MO 63110 USA. [Harold, Denise; Sims, Rebecca] Cardiff Univ, Inst Psychol Med & Clin Neurosci, Cardiff CF10 3AX, S Glam, Wales. [Graham, Rob; van der Brug, Marcel P.] Genentech Inc, Diagnost Discovery Dept, San Francisco, CA 94080 USA. [Bhangale, Tushar] Genentech Inc, Dept Bioinformat & Computat Biol, San Francisco, CA 94080 USA. [Ortmann, Ward; Behrens, Tim; Singleton, Andy; Hardy, John] Genentech Inc, Dept Human Genet, San Francisco, CA 94080 USA. [Guerreiro, Rita; Sassi, Celeste] UCL Inst Neurol, Dept Mol Neurosci, London, England. [Guerreiro, Rita; Gibbs, J. Raphael; Sassi, Celeste] NIA, Lab Neurogenet, NIH, Bethesda, MD 20892 USA. [Kauwe, John S. K.] Brigham Young Univ, Dept Biol, Provo, UT 84602 USA. [Mayeux, Richard] Columbia Univ, Taub Inst Alzheimers Dis & Aging Brain, Dept Neurol, New York, NY USA. [Mayeux, Richard] Columbia Univ, Gertrude H Sergievsky Ctr, New York, NY 10027 USA. [Pericak-Vance, Margaret A.] Univ Miami, John P Hussman Inst Human Genom, Miami, FL USA. [Pericak-Vance, Margaret A.] Univ Miami, Dr John T Macdonald Fdn, Dept Human Genet, Miami, FL USA. [Farrer, Lindsay A.] Boston Univ, Sch Med, Dept Med, Boston, MA 02118 USA. [Farrer, Lindsay A.] Boston Univ, Sch Publ Hlth, Dept Med, Boston, MA USA. [Farrer, Lindsay A.] Boston Univ, Sch Med, Dept Biomed Genet, Boston, MA 02118 USA. [Farrer, Lindsay A.] Boston Univ, Sch Publ Hlth, Dept Biomed Genet, Boston, MA USA. [Farrer, Lindsay A.] Boston Univ, Sch Med, Dept Neurol, Boston, MA 02118 USA. [Farrer, Lindsay A.] Boston Univ, Sch Publ Hlth, Dept Neurol, Boston, MA USA. [Farrer, Lindsay A.] Boston Univ, Sch Med, Dept Ophthalmol, Boston, MA 02118 USA. [Farrer, Lindsay A.] Boston Univ, Sch Publ Hlth, Dept Ophthalmol, Boston, MA USA. [Farrer, Lindsay A.] Boston Univ, Sch Med, Dept Epidemiol, Boston, MA 02118 USA. [Farrer, Lindsay A.] Boston Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA USA. [Farrer, Lindsay A.] Boston Univ, Sch Med, Dept Biostat, Boston, MA 02118 USA. [Farrer, Lindsay A.] Boston Univ, Sch Publ Hlth, Dept Biostat, Boston, MA USA. [Schellenberg, Gerard D.] Univ Penn, Perelman Sch Med, Dept Pathol & Lab Med, Philadelphia, PA 19104 USA. [Haines, Jonathan L.] Vanderbilt Univ, Vanderbilt Ctr Human Genet Res, Dept Mol Physiol & Biophys, Nashville, TN 37235 USA. [Lord, Jenny; Brown, Kristelle; Medway, Christopher; Braae, Anne; Barber, Imelda; Morgan, Kevin] Univ Nottingham, Sch Mol Med Sci, Nottingham NG7 2RD, England. [Lupton, Michelle K.; Powell, John] Kings Coll London, Inst Psychiat, London, England. [Lambert, Jean-Charles; Bellenguez, Celine; Amouyel, Philippe] INSERM, F-59045 Lille, France. [Lambert, Jean-Charles; Bellenguez, Celine; Amouyel, Philippe; Cruchaga, Carlos] Univ Lille 2, Lille, France. [Lambert, Jean-Charles; Bellenguez, Celine; Amouyel, Philippe] Inst Pasteur, F-59019 Lille, France. RP Cruchaga, C (reprint author), Washington Univ, Sch Med, Dept Psychiat, 660 South Euclid Ave B8134, St Louis, MO 63110 USA. EM goatea@psychiatry.wustl.edu; cruchagac@psychiatry.wustl.edu RI Tsuang, Debby/L-7234-2016; Hardy, John/C-2451-2009; Singleton, Andrew/C-3010-2009; Bras, Jose/A-1428-2011; Powell, John/G-4412-2011; lambert, jean-charles/F-8787-2013; Lambert, jean-charles/A-9553-2014; Guerreiro, Rita/A-1327-2011; Benitez, Bruno/E-7116-2014; OI Tsuang, Debby/0000-0002-4716-1894; Harold, Denise/0000-0001-5195-0143; Powell, John/0000-0001-6124-439X; Lambert, jean-charles/0000-0003-0829-7817; Bras, Jose/0000-0001-8186-0333; Farrer, Lindsay/0000-0001-5533-4225; Benitez, Bruno/0000-0002-2699-3878; Cruchaga, Carlos/0000-0002-0276-2899 FU French National Foundation on Alzheimer's disease and related disorders; LABEX (laboratory of excellence program investment for the future) DISTALZ grant (Development of Innovative Strategies for a Transdisciplinary approach to ALZheimer's disease); Caisse Nationale Maladie des Travailleurs Salaries; Direction Generale de la Sante; MGEN; Institut de la Longevite; Agence Francaise de Securite Sanitaire des Produits de Sante; Aquitaine and Bourgogne Regional Councils; Fondation de France; French Ministry of Research and INSERM "Cohortes et collections de donnees biologiques" programme FX EADI1 was supported by the French National Foundation on Alzheimer's disease and related disorders. Data management involved the Centre National de Genotypage, the Institut Pasteur de Lille, Inserm, FRC (fondation pour la recherche sur le cerveau), and Rotary. This work has been developed and supported by the LABEX (laboratory of excellence program investment for the future) DISTALZ grant (Development of Innovative Strategies for a Transdisciplinary approach to ALZheimer's disease). The Three-City Study was performed as part of collaboration between the Institut National de la Sante et de la Recherche Medicale (Inserm), the Victor Sega len Bordeaux II University, and Sanofi-Synthelabo. The Fondation pour la Recherche Medicale funded the preparation and initiation of the study. The 3C Study was also funded by the Caisse Nationale Maladie des Travailleurs Salaries, Direction Generale de la Sante, MGEN, Institut de la Longevite, Agence Francaise de Securite Sanitaire des Produits de Sante, the Aquitaine and Bourgogne Regional Councils, Fondation de France, and the joint French Ministry of Research and INSERM "Cohortes et collections de donnees biologiques" programme. Lille Genopo le received an unconditional grant from Eisai. NR 25 TC 18 Z9 18 U1 0 U2 12 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0197-4580 EI 1558-1497 J9 NEUROBIOL AGING JI Neurobiol. Aging PD JUN PY 2014 VL 35 IS 6 AR 1510.e19 DI 10.1016/j.neurobiolaging.2013.12.010 PG 8 WC Geriatrics & Gerontology; Neurosciences SC Geriatrics & Gerontology; Neurosciences & Neurology GA AE4RO UT WOS:000333970800035 PM 24439484 ER PT J AU Calvo, A Moglia, C Canosa, A Brunetti, M Barberis, M Traynor, BJ Carrara, G Valentini, C Restagno, G Chio, A AF Calvo, Andrea Moglia, Cristina Canosa, Antonio Brunetti, Maura Barberis, Marco Traynor, Bryan J. Carrara, Giovanna Valentini, Consuelo Restagno, Gabriella Chio, Adriano TI A de novo nonsense mutation of the FUS gene in an apparently familial amyotrophic lateral sclerosis case SO NEUROBIOLOGY OF AGING LA English DT Article DE Amyotrophic lateral sclerosis; FUS; de novo mutation ID HEXANUCLEOTIDE REPEAT; ALS; C9ORF72; AUTISM; SCHIZOPHRENIA; PHENOTYPE; FTD AB Mutations in C9ORF72, SOD1, TARDBP, and FUS genes account for approximately two-third of familial cases and 5% of sporadic amyotrophic lateral sclerosis (ALS) cases. We present the first case of an ALS patient carrying a de novo nonsense mutation in exon 14 of the FUS gene (c.1483c>t; p.R495X) with an apparently familial ALS. This mutation causes a phenotype characterized by a young age at onset, a rapid course (<24 months), and a bulbar onset with early respiratory involvement with a predominant lower motor neuron disease. De novo mutations could account for a sizable number of apparently sporadic ALS patients carrying mutations of ALS-related genes. (C) 2014 Elsevier Inc. All rights reserved. C1 [Calvo, Andrea; Moglia, Cristina; Canosa, Antonio; Chio, Adriano] Univ Turin, Rita Levi Montalcini Dept Neurosci, ALS Ctr, I-10126 Turin, Italy. [Brunetti, Maura; Barberis, Marco; Restagno, Gabriella] Azienda Osped Citta Salute & Sci, Mol Genet Lab, Turin, Italy. [Traynor, Bryan J.] NIA, Neuromuscular Dis Res Unit, Neurogenet Lab, NIH, Bethesda, MD 20892 USA. [Carrara, Giovanna; Valentini, Consuelo] Dept Neuroradiol, Azienda Osped Citta Salute & Sci, Dept Neuroradiol, Turin, Italy. [Chio, Adriano] Neurosci Inst Torino, Turin, Italy. RP Calvo, A (reprint author), Univ Turin, Rita Levi Montalcini Dept Neurosci, ALS Ctr, Via Cherasco 15, I-10126 Turin, Italy. EM achio@usa.net RI Calvo, Andrea/K-4141-2016; Moglia, Cristina/K-4142-2016; OI Calvo, Andrea/0000-0002-5122-7243; Moglia, Cristina/0000-0001-7377-7222; Chio, Adriano/0000-0001-9579-5341 FU Fondazione Vialli e Mauro for ALS Research Onlus; Federazione Italiana Giuoco Calcio; Ministero della Salute [RF-PIE-2007-635695, RF-2010-2309849]; Joint Programmed-Neurodegenerative Disease Research (Strength Project); European Community [259867]; Intramural Research Program of the National Institutes of Health and the National Institute on Aging [Z01 AG000949-02] FX Adriano Chio had full access to all the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis. We thank the patient and her family for having collaborated to this study. This work was funded by grants of Fondazione Vialli e Mauro for ALS Research Onlus, Federazione Italiana Giuoco Calcio, Ministero della Salute (Ricerca Sanitaria Finalizzata 2007, grant RF-PIE-2007-635695, and 2010, grant RF-2010-2309849), and Joint Programmed-Neurodegenerative Disease Research (Strength Project). The research leading to these results has received funding from the European Community's Health Seventh Framework Programme (FP7/2007-2013) (grant agreement no. 259867). This work was supported in part by the Intramural Research Program of the National Institutes of Health and the National Institute on Aging (project Z01 AG000949-02). Funding organizations had no role in design and conduct of the study; collection, management, analysis, and interpretation of the data; and preparation, review, or approval of the manuscript. NR 31 TC 3 Z9 3 U1 0 U2 3 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0197-4580 EI 1558-1497 J9 NEUROBIOL AGING JI Neurobiol. Aging PD JUN PY 2014 VL 35 IS 6 AR 1513.e7 DI 10.1016/j.neurobiolaging.2013.12.028 PG 5 WC Geriatrics & Gerontology; Neurosciences SC Geriatrics & Gerontology; Neurosciences & Neurology GA AE4RO UT WOS:000333970800042 PM 24439481 ER PT J AU Dong, J Gao, JJ Nalls, M Gao, X Huang, XM Han, JL Singleton, AB Chen, HL AF Dong, Jing Gao, Jianjun Nalls, Michael Gao, Xiang Huang, Xuemei Han, Jiali Singleton, Andrew B. Chen, Honglei CA IPDGC TI Susceptibility loci for pigmentation and melanoma in relation to Parkinson's disease SO NEUROBIOLOGY OF AGING LA English DT Article DE Pigmentation; Melanoma; Parkinson's disease; Susceptibility ID GENOME-WIDE ASSOCIATION; GENETIC-DETERMINANTS; RISK; CANCER; METAANALYSIS; EUROPEANS; VARIANTS; HAIR AB Growing evidence suggests that Parkinson's disease (PD) patients have a lower risk for most types of cancer except for melanoma, which has a modest positive association with PD. Pigmentation genes have been hypothesized to contribute to this association. We therefore examined whether genetic susceptibility loci for pigmentation or melanoma was associated with PD risk in 2 large independent datasets. In the Parkinson's Genes and Environment (PAGE) study, we examined 11 single-nucleotide polymorphisms (SNPs) identified from previous genome-wide association studies (GWAS) of pigmentation or melanoma in relation to PD among 808 PD cases and 1623 controls; furthermore, we also examined the colors of hair, eye, or skin and melanoma in relation to PD. In the International Parkinson's Disease Genomic Consortium (IPDGC), we examined a broader selection of 360 pigmentation or melanoma GWAS SNPs in relation to PD among 5,333 PD cases and 12,019 controls. All participants were non-Hispanic Whites. As expected, in the PAGE study, most SNPs were associated with 1 or more pigmentation phenotypes. However, neither these SNPs nor pigmentation phenotypes were associated with PD risk after Bonferroni correction with the exception of rs4911414 at the ASIP gene (p.001). A total of 18 PD cases (2.2%) and 26 controls (1.6%) had a diagnosis of melanoma with an odds ratio of 1.3 (95% confidence interval: 0.7-2.4). In the IPDGC analysis, none of the 360 SNPs, including rs4911414, were associated with PD risk after adjusting for multiple comparisons. In conclusion, we did not find significant associations between GWAS SNPs of pigmentation or melanoma and the risk for PD. Published by Elsevier Inc. C1 [Dong, Jing; Gao, Jianjun; Chen, Honglei] NIEHS, Epidemiol Branch, Res Triangle Pk, NC 27709 USA. [Gao, Jianjun] Univ Chicago, Dept Hlth Studies, Chicago, IL 60637 USA. [Nalls, Michael; Singleton, Andrew B.] NIA, Neurogenet Lab, Bethesda, MD 20892 USA. [Gao, Xiang] Harvard Univ, Sch Publ Hlth, Dept Nutr, Boston, MA 02115 USA. [Gao, Xiang] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. [Gao, Xiang; Han, Jiali] Harvard Univ, Sch Med, Channing Lab, Boston, MA 02115 USA. [Huang, Xuemei] Penn State Univ, Milton S Hershey Med Ctr, Hershey, PA 17033 USA. RP Chen, HL (reprint author), NIEHS, Epidemiol Branch, 111 TW Alexander Dr,POB 12233,Mail Drop A3-05, Res Triangle Pk, NC 27709 USA. EM chenh2@niehs.nih.gov RI Bloem, B.R./H-8013-2014; Wood, Nicholas/C-2505-2009; van de Warrenburg, Bart/D-1935-2010; Martinez, Maria/B-3111-2013; Guerreiro, Rita/A-1327-2011; corvol, jean-christophe/I-6387-2012; Revesz, Tamas/A-8732-2010; Trabzuni, Daniah/C-4034-2012; Deuschl, Gunther/A-7986-2010; Lees, Andrew/A-6605-2009; Scheffer, Hans/E-4644-2012; Hardy, John/C-2451-2009; Cooper, J Mark/D-5826-2013; Schapira, Anthony/A-1245-2010; Singleton, Andrew/C-3010-2009; Bras, Jose/A-1428-2011; Deloukas, Panos/B-2922-2013; Morris, Huw/B-8527-2008; OI Wood, Nicholas/0000-0002-9500-3348; Martinez, Maria/0000-0003-2180-4537; corvol, jean-christophe/0000-0001-7325-0199; Revesz, Tamas/0000-0003-2501-0259; Trabzuni, Daniah/0000-0003-4826-9570; Bras, Jose/0000-0001-8186-0333; Plagnol, Vincent/0000-0002-5597-9215; Scheffer, Hans/0000-0002-2986-0915; Cooper, J Mark/0000-0002-3007-3054; Schapira, Anthony/0000-0002-3018-3966; Deloukas, Panos/0000-0001-9251-070X; Morris, Huw/0000-0002-5473-3774; Bhatia, Kailash/0000-0001-8185-286X; Chen, Honglei/0000-0003-3446-7779 FU Intramural Research Program of the NIH; National Institute of Environmental Health Sciences [Z01-ES-101986]; National Cancer Institute [Z01-CP010196-02]; National Institute on Aging [Z01-AG000949-02] FX The authors are grateful to the continuous contribution of participants of the PAGE study and the International PD Genomic Consortium. We also thank investigators from the NIH-AARP Diet and Health Study for their continuous support. This study was supported by the Intramural Research Program of the NIH, the National Institute of Environmental Health Sciences (Z01-ES-101986), the National Cancer Institute (Z01-CP010196-02), and the National Institute on Aging (Z01-AG000949-02). NR 20 TC 8 Z9 8 U1 1 U2 18 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0197-4580 EI 1558-1497 J9 NEUROBIOL AGING JI Neurobiol. Aging PD JUN PY 2014 VL 35 IS 6 AR 1512.e5 DI 10.1016/j.neurobiolaging.2013.12.020 PG 6 WC Geriatrics & Gerontology; Neurosciences SC Geriatrics & Gerontology; Neurosciences & Neurology GA AE4RO UT WOS:000333970800039 PM 24439955 ER PT J AU Mondul, AM Weinstein, SJ Moy, KA Mannisto, S Albanes, D AF Mondul, Alison M. Weinstein, Stephanie J. Moy, Kristin A. Mannisto, Satu Albanes, Demetrius TI Vitamin D- binding protein, circulating vitamin D and risk of renal cell carcinoma SO INTERNATIONAL JOURNAL OF CANCER LA English DT Article DE renal cell carcinoma; vitamin D-binding protein; 25-hydroxyvitamin D; prospective studies ID 25-HYDROXYVITAMIN D; PANCREATIC-CANCER; PROSTATE-CANCER; KIDNEY CANCER; ASSOCIATION; COHORT; TRIAL AB Cell culture experiments suggest that vitamin D may inhibit renal carcinogenesis, but human studies of circulating 25-hydroxyvitamin D [25(OH)D], the accepted measure of vitamin D status, and kidney cancer have been null. Limited research has examined the role of circulating vitamin D-binding protein (DBP) in the association between 25(OH)D and disease risk, and it is unclear whether free 25(OH)D in circulation is a better measure of effective exposure, or if DBP may independently impact outcomes. We conducted a nested case-control analysis within the Alpha-Tocopherol, Beta-Carotene Cancer Prevention (ATBC) Study to examine whether circulating DBP concentration was prospectively associated with risk of renal cell carcinoma, and whether it modified the association with 25(OH)D. Renal cell carcinoma cases (n = 262) were matched 1:1 to controls on age (1 year) and date of blood collection ( 30 days). We estimated odds ratios (ORs) and 95% confidence intervals (CIs) of renal cell carcinoma risk by quartiles of 25(OH)D, DBP and the molar ratio of 25(OH)D:DBP, a proxy for free circulating 25(OH)D. Men with higher DBP concentrations were at significantly decreased risk of kidney cancer (Q4 vs. Q1: OR = 0.17, 95% CI = 0.08-0.33; p-trend < 0.0001), a finding unchanged by adjustment for 25(OH)D. Although we observed no association with total 25(OH)D, we found slightly increased risk with higher levels of estimated free 25(OH)D [Q4 vs. Q1 of the 25(OH)D:DBP ratio, OR = 1.61, 95% CI = 0.95-2.73; p-trend = 0.09]. The strong protective association observed between higher circulating DBP concentration and kidney cancer risk requires replication but suggests a vitamin D-independent influence of DBP. What's new? Circulating vitamin D binding protein (DBP) has been implicated in the etiology of certain cancers, where it may act directly or by modifying circulating vitamin D concentrations and disease risk. In this examination of the association between DBP and renal cell carcinoma (RCC) specifically, a strong protective association was found between elevated circulating DBP concentrations and kidney cancer. The association was unchanged after adjustment for circulating vitamin D. The results suggest that DBP may influence risk of RCC through a biologic mechanism unrelated to vitamin D status. C1 [Mondul, Alison M.; Weinstein, Stephanie J.; Moy, Kristin A.; Albanes, Demetrius] NCI, Nutrit Epidemiol Branch, Div Canc Epidemiol & Genet, NIH, Rockville, MD 20892 USA. [Mannisto, Satu] Natl Inst Hlth & Welf, Dept Chron Dis Prevent, Helsinki, Finland. RP Mondul, AM (reprint author), NCI, Nutrit Epidemiol Branch, Div Canc Epidemiol & Genet, NIH, Bethesda, MD 20892 USA. EM mondulam@mail.nih.gov RI Albanes, Demetrius/B-9749-2015; OI Mondul, Alison/0000-0002-8843-1416; Mannisto, Satu/0000-0002-8668-3046 FU Intramural NIH HHS [Z99 CA999999] NR 24 TC 14 Z9 14 U1 0 U2 13 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0020-7136 EI 1097-0215 J9 INT J CANCER JI Int. J. Cancer PD JUN 1 PY 2014 VL 134 IS 11 BP 2699 EP 2706 DI 10.1002/ijc.28596 PG 8 WC Oncology SC Oncology GA AC8RO UT WOS:000332801700019 PM 24214881 ER PT J AU Hiram-Bab, S Katz, LS Shapira, H Sandbank, J Gershengorn, MC Oron, Y AF Hiram-Bab, Sahar Katz, Liora S. Shapira, Hagit Sandbank, Judith Gershengorn, Marvin C. Oron, Yoram TI Platelet- Derived Growth Factor BB Mimics Serum- Induced Dispersal of Pancreatic Epithelial Cell Clusters SO JOURNAL OF CELLULAR PHYSIOLOGY LA English DT Article ID INSULIN-PRODUCING CELLS; MESENCHYMAL STEM-CELLS; PRECURSOR CELLS; EMBRYONIC STEM; BETA-CATENIN; IN-VITRO; PROGENITOR CELLS; BONE-MARROW; MULTIPOTENTIAL NESTIN; SIGNALING PATHWAY AB We showed previously that proliferating human islet-derived de-differentiated cells (DIDs) exhibit many characteristics of mesenchymal stem cells. Dispersed DIDs can be induced by serum deprivation to undergo mesenchymal-to-epithelial transition and aggregate into epithelial cell clusters (ECCs). Conversely, ECCs can be induced to disperse and undergo epithelial-to-mesenchymal transition (EMT) by re-addition of mammalian sera. In this study, we show that platelet-derived growth factor BB (PDGF-BB) mimics and mediates serum-induced ECCs' dispersal accompanied by accumulation of cytoplasmic -catenin and a decrease in the levels of insulin and glucagon mRNAs. Moreover, we show that PDGF-BB-induced dispersal of ECCs is a more general phenomenon that occurs also with bone marrow mesenchymal stem cells (BM-MSCs) and dermal fibroblasts (DFs). In DIDs, BM-MSCs, and DFs, PDGF decreased the levels of DKK1 mRNA, suggesting involvement of the Wnt signaling pathway. PDGF-BB stimulated a significant increase in S473 phosphorylation of Akt and the PI3K specific inhibitor (PIP828) partially inhibited PDGF-BB-induced ECC dispersal. Lastly, the PDGF-receptor (PDGF-R) antagonist JNJ-10198409 inhibited both PDGF-BBand serum-induced ECC dispersal. Epidermal growth factor (EGF), which shares most of the PDGF signaling pathway, did not induce dispersal and only weakly stimulated Akt phosphorylation. Our data suggest that PDGF-BB mediates serum-induced DIDs dispersal, correlated with the activation of the PI3K-Akt pathway. J. Cell. Physiol. 229: 743-751, 2014. (c) 2013 Wiley Periodicals, Inc. C1 [Hiram-Bab, Sahar; Oron, Yoram] Tel Aviv Univ, Sackler Fac Med, Dept Physiol & Pharmacol, IL-69978 Tel Aviv, Israel. [Katz, Liora S.; Gershengorn, Marvin C.] NIDDK, Lab Endocrinol & Receptor Biol, NIH, Bethesda, MD 20892 USA. [Shapira, Hagit; Sandbank, Judith] Maccabi Hlth Org, Cent Lab, Inst Pathol, Rehovot, Israel. [Sandbank, Judith] Tel Aviv Univ, Sackler Fac Med, Dept Pathol, IL-69978 Tel Aviv, Israel. RP Oron, Y (reprint author), Tel Aviv Univ, Sackler Fac Med, Dept Physiol & Pharmacol, IL-69978 Tel Aviv, Israel. EM medfair@post.tau.ac.il FU Intramural Research Program NIDDK; NIH [Z01 DK011007]; SNSF [PBGEP3-139875] FX Contract grant sponsor: Intramural Research Program NIDDK.; Contract grant sponsor: NIH;; Contract grant number: Z01 DK011007.; Contract grant sponsor: SNSF;; Contract grant number: PBGEP3-139875. NR 69 TC 1 Z9 1 U1 0 U2 12 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0021-9541 EI 1097-4652 J9 J CELL PHYSIOL JI J. Cell. Physiol. PD JUN PY 2014 VL 229 IS 6 BP 743 EP 751 DI 10.1002/jcp.24493 PG 9 WC Cell Biology; Physiology SC Cell Biology; Physiology GA AB7YP UT WOS:000332007600007 PM 24129818 ER PT J AU Kang, N Won, M Rhee, M Ro, H AF Kang, Nami Won, Minho Rhee, Myungchull Ro, Hyunju TI Siah Ubiquitin Ligases Modulate Nodal Signaling during Zebrafish Embryonic Development SO MOLECULES AND CELLS LA English DT Article DE antivin/Lft1; body patterning; FoxH1/Fast1; Nodal; Siah2; zebrafish ID 7 IN-ABSENTIA; TGF-BETA; TRANSCRIPTIONAL REPRESSOR; CELL-DIFFERENTIATION; GENE-EXPRESSION; DEGRADATION; ORGANIZER; HOMOLOG; ACTIVIN; PROTEIN AB Siah2 is a zebrafish homologue of mammalian Siah family. Siah acts as an E3 ubiquitin ligase that binds proteins destined for degradation. Extensive homology between siah and Drosophila Siah homologue (sina) suggests their important physiological roles during embryonic development. However, detailed functional studies of Siah in vertebrate development have not been carried out. Here we report that Siah2 specifically augments nodal related gene expression in marginal blastomeres at late blastula through early gastrula stages of zebrafish embryos. Siah2 dependent Nodal signaling augmentation is confirmed by cell-based reporter gene assays using 293T cells and 3TPluciferase reporter plasmid. We also established a molecular hierarchy of Siah as a upstream regulator of FoxH1/Fast1 transcriptional factor in Nodal signaling. Elevated expression of nodal related genes by overexpression of Siah2 was enough to override the inhibitory effects of atv and lft2 on the Nodal signaling. In particular, E3 ubiquitin ligase activity of Siah2 is critical to limit the duration and/or magnitude of Nodal signaling. Additionally, since the embryos injected with Siah morpholinos mimicked the atv overexpression phenotype at least in part, our data support a model in which Siah is involved in mesendoderm patterning via modulating Nodal signaling. C1 [Kang, Nami; Rhee, Myungchull; Ro, Hyunju] Chungnam Natl Univ, Dept Biol Sci, Coll Biosci & Biotechnol, Taejon 305764, South Korea. [Won, Minho] Eunice Kennedy Shiver Natl Inst Child Hlth & Huma, Program Genom Differentiat, NIH, Bethesda, MD USA. RP Rhee, M (reprint author), Chungnam Natl Univ, Dept Biol Sci, Coll Biosci & Biotechnol, Taejon 305764, South Korea. EM mrhee@cnu.ac.kr; rohyunju@cnu.ac.kr FU Basic Science Research Program through the National Research Foundation of Korea (NRF) - Ministry of Education, Science and Technology [NRF-2012R1A1A4A01012264] FX We thank I. B. Dawid (NIH-NICHD, USA) for the valuable comments for and thorough reading of our manuscript. This research was supported by Basic Science Research Program through the National Research Foundation of Korea (NRF) funded by the Ministry of Education, Science and Technology (NRF-2012R1A1A4A01012264). NR 48 TC 3 Z9 3 U1 0 U2 2 PU KOREAN SOC MOLECULAR & CELLULAR BIOLOGY PI SEOUL PA 635-4, YUCKSAM-DONG, GANGNAM-GU, SEOUL 135-703, SOUTH KOREA SN 1016-8478 EI 0219-1032 J9 MOL CELLS JI Mol. Cells PD MAY 31 PY 2014 VL 37 IS 5 BP 389 EP 398 DI 10.14348/molcells.2014.0032 PG 10 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA AQ1SF UT WOS:000342560600005 PM 24823357 ER PT J AU Wu, WT Jin, M Wang, YJ Liu, BY Shen, DF Chen, P Hannes, S Li, ZY Hirani, SM Jawad, S Sen, HN Chan, CC Nussenblatt, RB Wei, L AF Wu, Wenting Jin, Ming Wang, Yujuan Liu, Baoying Shen, Defen Chen, Ping Hannes, Susan Li, Zhiyu Hirani, Sima Jawad, Shayma Sen, H. Nida Chan, Chi-Chao Nussenblatt, Robert B. Wei, Lai CA Unite Human Ocular Inflammat Conso TI Overexpression of IL-17RC associated with ocular sarcoidosis SO JOURNAL OF TRANSLATIONAL MEDICINE LA English DT Article DE Ocular sarcoidosis; IL-17RC; CD8 ID GENOME-WIDE ASSOCIATION; CD4(+) T-CELLS; SUSCEPTIBILITY; MYCOBACTERIAL; DISEASES; UVEITIS; BTNL2; GENE AB Background: Sarcoidosis is a chronic inflammatory disease with a systemic granulomatous disorder affecting multiple organs including the eye. Both CD4(+) T cell and macrophage have been linked to the pathogenesis of the disease. Methods: The expression of IL-17RC was measured using FACS, immunohistochemistry and real-time PCR. Serum level of IL-17 was detected using ELISA. Results: An elevated expression of IL-17RC on CD8(+) T cells in peripheral blood was found in patients with ocular sarcoidosis as compared to healthy controls. Interestingly, we found a significant increase in the serum level of IL-17 in patients with ocular sarcoidosis as compared to healthy controls, which may be responsible for the induction of IL-17RC on CD8(+) cells. In addition, IL-17RC appeared only in the retinal tissue of the patient with clinically active sarcoidosis. Conclusions: Our results suggested a potential involvement of IL-17RC(+) CD8(+) T cells in pathogenesis of ocular sarcoidosis. C1 [Wu, Wenting; Wang, Yujuan; Liu, Baoying; Shen, Defen; Chen, Ping; Hannes, Susan; Li, Zhiyu; Hirani, Sima; Jawad, Shayma; Sen, H. Nida; Chan, Chi-Chao; Nussenblatt, Robert B.; Wei, Lai] NEI, Immunol Lab, NIH, Bethesda, MD 20892 USA. [Wu, Wenting] Beijing Univ Chinese Med, Beijing, Peoples R China. [Wu, Wenting; Jin, Ming] China Japan Friendship Hosp, Dept Ophthalmol, Beijing, Peoples R China. [Wang, Yujuan; Wei, Lai] Sun Yat Sen Univ, State Key Lab Ophthalmol, Zhongshan Ophthalm Ctr, Guangzhou 510275, Guangdong, Peoples R China. RP Nussenblatt, RB (reprint author), NEI, Immunol Lab, NIH, Bldg 10, Bethesda, MD 20892 USA. EM drbob@nei.nih.gov; weil9@mail.sysu.edu.cn RI wang, yujuan/C-8428-2016 FU intramural research program of NEI; NCCAM FX This study is supported by the intramural research program of NEI and NCCAM. NR 33 TC 7 Z9 7 U1 1 U2 5 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 MAY 31 PY 2014 VL 12 AR 152 DI 10.1186/1479-5876-12-152 PG 6 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA AK5NO UT WOS:000338471800001 PM 24885153 ER PT J AU Spottiswoode, N Duffy, PE Drakesmith, H AF Spottiswoode, Natasha Duffy, Patrick E. Drakesmith, Hal TI Iron, anemia and hepcidin in malaria SO FRONTIERS IN PHARMACOLOGY LA English DT Review DE hepcidin; malaria; iron; anemia; global health ID PLASMODIUM-FALCIPARUM MALARIA; ANTIMICROBIAL PEPTIDE HEPCIDIN; CONTROLLED-TRIAL; YOUNG-CHILDREN; SALMONELLA INFECTIONS; HELMINTH INFECTIONS; PRESCHOOL-CHILDREN; INTRACELLULAR IRON; CHELATION-THERAPY; DEFICIENCY ANEMIA AB Malaria and iron have a complex but important relationship. Plasmodium proliferation requires iron, both during the clinically silent liver stage of growth and in the disease-associated phase of erythrocyte infection. Precisely how the protozoan acquires its iron from its mammalian host remains unclear, but iron chelators can inhibit pathogen growth in vitro and in animal models. In humans, iron deficiency appears to protect against severe malaria, while iron supplementation increases risks of infection and disease. Malaria itself causes profound disturbances in physiological iron distribution and utilization, through mechanisms that include hemolysis, release of heme, dyserythropoiesis, anemia, deposition of iron in macrophages, and inhibition of dietary iron absorption. These effects have significant consequences. Malarial anemia is a major global health problem, especially in children, that remains incompletely understood and is not straightforward to treat. Furthermore, the changes in iron metabolism during a malaria infection may modulate susceptibility to co-infections. The release of heme and accumulation of iron in granulocytes may explain increased vulnerability to non-typhoidal Salmonella during malaria. The redistribution of iron away from hepatocytes and into macrophages may confer host resistance to superinfection, whereby blood-stage parasitemia prevents the development of a second liver-stage Plasmodium infection in the same organism. Key to understanding the pathophysiology of iron metabolism in malaria is the activity of the iron regulatory hormone hepcidin. Hepcidin is upregulated during blood-stage parasitemia and likely mediates much of the iron redistribution that accompanies disease. Understanding the regulation and role of hepcidin may offer new opportunities to combat malaria and formulate better approaches to treat anemia in the developing world. C1 [Spottiswoode, Natasha; Duffy, Patrick E.] NIAID, Lab Malaria Immunol & Vaccinol, NIH, Bethesda, MD 20892 USA. [Spottiswoode, Natasha; Drakesmith, Hal] Univ Oxford, Weatherall Inst Mol Med, MRC, Human Immunol Unit, Oxford OX3 9DS, England. RP Drakesmith, H (reprint author), Univ Oxford, Weatherall Inst Mol Med, MRC, Human Immunol Unit, Oxford OX3 9DS, England. EM hdrakes@hammer.imm.ox.ac.uk FU Intramural Research Program of NIAID, NIH; NIH Oxford - Cambridge Scholars Program; Medical Research Council, UK; Bill and Melinda Gates Foundation FX Natasha Spottiswoode and Patrick E. Duffy are supported by the Intramural Research Program of NIAID, NIH. Natasha Spoutswoode was also supported through the NIH Oxford - Cambridge Scholars Program during the period of writing. Hal Drakesmith is supported by the Medical Research Council, UK and by the Bill and Melinda Gates Foundation. NR 105 TC 22 Z9 23 U1 4 U2 13 PU FRONTIERS RESEARCH FOUNDATION PI LAUSANNE PA PO BOX 110, LAUSANNE, 1015, SWITZERLAND SN 1663-9812 J9 FRONT PHARMACOL JI Front. Pharmacol. PD MAY 30 PY 2014 VL 5 AR 125 DI 10.3389/fphar.2014.00125 PG 11 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA AX7KE UT WOS:000347094100001 PM 24910614 ER PT J AU Yazawa, I AF Yazawa, Itaru TI Reciprocal functional interactions between the brainstem and the lower spinal cord SO FRONTIERS IN NEUROSCIENCE LA English DT Article DE entrainment; hyperoxic/normocapnic state; locomotion; locomotor pattern generator; respiration ID RESPIRATORY RHYTHM ENTRAINMENT; CENTRAL CHEMOSENSITIVITY; IN-VITRO; RAT; STIMULATION; EXERCISE; VASOPRESSIN; MOUSE; BARORECEPTORS; CONTRACTIONS AB The interplay of the neuronal discharge patterns regarding respiration and locomotion was investigated using electrophysiological techniques in a decerebrate and arterially perfused in situ mouse preparation. The phrenic, tibial, and/or peroneal nerve discharge became clearly organized into discharge episodes of increasing frequency and duration, punctuated by periods of quiescence as the perfusion flow rate increased at room temperature. The modulated sympathetic tone induced by the hyperoxic/normocapnic state was found to activate the locomotor pattern generator (LPG) via descending pathways and generate a left and right alternating discharge during discharge episodes in the motor nerves. The rhythm coupling of respiration and locomotion occurred at a 1:1 frequency ratio. Although the phrenic discharge synchronized with the tibial discharge at all flow rates tested, the time lag between peaks of the two discharges during locomotion was approximate to 400 ms rather than approximate to 200 ms, suggesting spinal feedback via ascending pathways. The incidence of the phrenic and tibial discharge episodes decreased by approximate to 50% after spinalization at the twelfth thoracic cord and the respiratory rhythm was more regular. These results indicate that: (i) locomotion can be generated in a hyperoxic/normocapnic state induced by specific respiratory conditions, (ii) the central mechanism regarding entrainment of respiratory and locomotor rhythms relies on spinal feedback via ascending pathways, initiated by the activated LPG generating locomotion, and (iii) the increase in respiratory rate seen during locomotion is caused not only by afferent mechanical and nociceptive inputs but also by impulses from the activated spinal cord producing a locomotor-like discharge via ascending pathways. C1 [Yazawa, Itaru] NINDS, Neural Control Lab, NIH, Bethesda, MD 20892 USA. RP Yazawa, I (reprint author), Showa Univ, Sch Dent, Dept Oral Physiol, Shinagawa Ku, 1-5-8 Hatanodai, Tokyo 1428555, Japan. EM yazawa-ns@umin.ac.jp FU National Institute of Neurological Disorders and Stroke FX This work was supported by the intramural program of the National Institute of Neurological Disorders and Stroke. I thank Dr. A. E. Pickering for his helpful comments regarding the manuscript. NR 40 TC 4 Z9 4 U1 1 U2 1 PU FRONTIERS RESEARCH FOUNDATION PI LAUSANNE PA PO BOX 110, LAUSANNE, 1015, SWITZERLAND SN 1662-453X J9 FRONT NEUROSCI-SWITZ JI Front. Neurosci. PD MAY 30 PY 2014 VL 8 AR 124 DI 10.3389/fnins.2014.00124 PG 12 WC Neurosciences SC Neurosciences & Neurology GA AW8BB UT WOS:000346484500001 PM 24910591 ER PT J AU Barroso, M Florindo, C Kalwa, H Silva, Z Turanov, AA Carlson, BA de Almeida, IT Blom, HJ Gladyshev, VN Hatfield, DL Michel, T Castro, R Loscalzo, J Handy, DE AF Barroso, Madalena Florindo, Cristina Kalwa, Hermann Silva, Zelia Turanov, Anton A. Carlson, Bradley A. de Almeida, Isabel Tavares Blom, Henk J. Gladyshev, Vadim N. Hatfield, Dolph L. Michel, Thomas Castro, Rita Loscalzo, Joseph Handy, Diane E. TI Inhibition of Cellular Methyltransferases Promotes Endothelial Cell Activation by Suppressing Glutathione Peroxidase 1 Protein Expression SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article DE Cell Adhesion; Endothelial Cell; Glutathione Peroxidase; Oxidative Stress; Selenoprotein; S-Adenosylhomocysteine; tRNA Methylation ID S-ADENOSYLHOMOCYSTEINE CONCENTRATIONS; INTERCELLULAR-ADHESION MOLECULE-1; SELENOCYSTEINE TRANSFER-RNA; THIOREDOXIN REDUCTASE; HYDROGEN-PEROXIDE; CARDIOVASCULAR EVENTS; ARGININE METHYLATION; DNA HYPOMETHYLATION; VASCULAR-DISEASE; OXIDATIVE STRESS AB Background: Methylation of tRNA(Sec) facilitates the incorporation of selenocysteine at a UGA codon during translation. Results: Accumulation of the homocysteine precursor S-adenosylhomocysteine decreases tRNA(Sec) methylation, reducing glutathione peroxidase 1 expression and increasing oxidative stress-induced inflammatory activation of endothelial cells. Conclusion: Methylation modulates the expression of selenoproteins to regulate redox-dependent inflammatory pathways. Significance: Hypomethylation stress promotes a proatherogenic endothelial cell phenotype. S-Adenosylhomocysteine (SAH) is a negative regulator of most methyltransferases and the precursor for the cardiovascular risk factor homocysteine. We have previously identified a link between the homocysteine-induced suppression of the selenoprotein glutathione peroxidase 1 (GPx-1) and endothelial dysfunction. Here we demonstrate a specific mechanism by which hypomethylation, promoted by the accumulation of the homocysteine precursor SAH, suppresses GPx-1 expression and leads to inflammatory activation of endothelial cells. The expression of GPx-1 and a subset of other selenoproteins is dependent on the methylation of the tRNA(Sec) to the Um34 form. The formation of methylated tRNA(Sec) facilitates translational incorporation of selenocysteine at a UGA codon. Our findings demonstrate that SAH accumulation in endothelial cells suppresses the expression of GPx-1 to promote oxidative stress. Hypomethylation stress, caused by SAH accumulation, inhibits the formation of the methylated isoform of the tRNA(Sec) and reduces GPx-1 expression. In contrast, under these conditions, the expression and activity of thioredoxin reductase 1, another selenoprotein, is increased. Furthermore, SAH-induced oxidative stress creates a proinflammatory activation of endothelial cells characterized by up-regulation of adhesion molecules and an augmented capacity to bind leukocytes. Taken together, these data suggest that SAH accumulation in endothelial cells can induce tRNA(Sec) hypomethylation, which alters the expression of selenoproteins such as GPx-1 to contribute to a proatherogenic endothelial phenotype. C1 [Barroso, Madalena; Kalwa, Hermann; Michel, Thomas; Loscalzo, Joseph; Handy, Diane E.] Brigham & Womens Hosp, Dept Med, Div Cardiovasc, Boston, MA 02115 USA. [Turanov, Anton A.; Gladyshev, Vadim N.] Brigham & Womens Hosp, Dept Med, Div Genet, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. [Barroso, Madalena; Florindo, Cristina; de Almeida, Isabel Tavares; Castro, Rita] Univ Lisbon, Res Inst Med & Pharmaceut Sci iMed UL, Fac Pharm, P-1649004 Lisbon, Portugal. [de Almeida, Isabel Tavares; Castro, Rita] Univ Lisbon, Fac Pharm, Dept Biochem & Human Biol, P-1649004 Lisbon, Portugal. [Silva, Zelia] Univ Nova Lisboa, Fac Ciencias Med, Dept Imunol, Chron Dis Res Ctr, P-1099085 Lisbon, Portugal. [Carlson, Bradley A.; Hatfield, Dolph L.] NCI, Mol Biol Selenium Sect, Mouse Canc Genet Program, NIH, Bethesda, MD 20892 USA. [Blom, Henk J.] Univ Hosp, Ctr Pediat & Adolescent Med, Dept Gen Pediat, D-79106 Freiburg, Germany. RP Handy, DE (reprint author), Brigham & Womens Hosp, Dept Med, Div Cardiovasc, 77 Ave Louis Pasteur, Boston, MA 02115 USA. EM dhandy@rics.bwh.harvard.edu RI Castro, Rita /G-7731-2011; silva, zelia/O-7243-2015; iMed.ULisboa, iMed.ULisboa/C-6292-2014; iMed.ULisboa, MetGen /B-5293-2014; Faculdade de Ciencias Medicas, Nova Medical School/K-6209-2013; OI Castro, Rita /0000-0002-4585-0741; silva, zelia/0000-0001-6660-426X; Blom, Henk/0000-0001-5202-9241; Florindo, Cristina/0000-0002-0664-5411 FU National Institutes of Health [HL067195, HL070819, HL048743, HL107192, HL108630, HL46457, HL48743, GM061603]; American Heart Association; Portuguese Fundacao para a Ciencia e a Tecnologia [PTDC/SAU-ORG/112683/2009, SFRH/BD/73021/2010] FX This work was supported, in whole or in part, by National Institutes of Health Grants HL067195, HL070819, HL048743, HL107192, and HL108630 (to J. L.); HL46457 and HL48743 (to T. M.); and GM061603 (to V. N. G.). This work was also supported by an American Heart Association postdoctoral fellowship grant (to H. K.) and by Portuguese Fundacao para a Ciencia e a Tecnologia Grants PTDC/SAU-ORG/112683/2009 (to R. C.) and SFRH/BD/73021/2010 (M. B.). NR 65 TC 7 Z9 7 U1 1 U2 12 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 EI 1083-351X J9 J BIOL CHEM JI J. Biol. Chem. PD MAY 30 PY 2014 VL 289 IS 22 BP 15350 EP 15362 DI 10.1074/jbc.M114.549782 PG 13 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA AJ2DL UT WOS:000337465400019 PM 24719327 ER PT J AU Bollmann, F Wu, ZX Oelze, M Siuda, D Xia, N Henke, J Daiber, A Li, HG Stumpo, DJ Blackshear, PJ Kleinert, H Pautz, A AF Bollmann, Franziska Wu, Zhixiong Oelze, Matthias Siuda, Daniel Xia, Ning Henke, Jenny Daiber, Andreas Li, Huige Stumpo, Deborah J. Blackshear, Perry J. Kleinert, Hartmut Pautz, Andrea TI Endothelial Dysfunction in Tristetraprolin-deficient Mice Is Not Caused by Enhanced Tumor Necrosis Factor-alpha Expression SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article DE Atherosclerosis; Endothelial Dysfunction; NADPH Oxidase; Reactive Nitrogen Species; Reactive Oxygen Species (ROS); Tumor Necrosis Factor (TNF) ID FINGER PROTEIN TRISTETRAPROLIN; MESSENGER-RNA TURNOVER; NITRIC-OXIDE SYNTHASE; RHEUMATOID-ARTHRITIS; GENE-EXPRESSION; TNF-ALPHA; CARDIOVASCULAR MORTALITY; REDUCES ATHEROSCLEROSIS; CHRONIC INFLAMMATION; VASCULAR-DISEASE AB Cardiovascular events are important co-morbidities in patients with chronic inflammatory diseases like rheumatoid arthritis. Tristetraprolin (TTP) regulates pro-inflammatory processes through mRNA destabilization and therefore TTP-deficient mice (TTP-/- mice) develop a chronic inflammation resembling human rheumatoid arthritis. We used this mouse model to evaluate molecular signaling pathways contributing to the enhanced atherosclerotic risk in chronic inflammatory diseases. In the aorta of TTP-/- mice we observed elevated mRNA expression of known TTP targets like tumor necrosis factor- (TNF-) and macrophage inflammatory protein-1, as well as of other pro-atherosclerotic mediators, like Calgranulin A, Cathepsin S, and Osteopontin. Independent of cholesterol levels TTP-/- mice showed a significant reduction of acetylcholine-induced, nitric oxide-mediated vasorelaxation. The endothelial dysfunction in TTP-/- mice was associated with increased levels of reactive oxygen and nitrogen species (RONS), indicating an enhanced nitric oxide inactivation by RONS in the TTP-/- animals. The altered RONS generation correlates with increased expression of NADPH oxidase 2 (Nox2) resulting from enhanced Nox2 mRNA stability. Although TNF- is believed to be a central mediator of inflammation-driven atherosclerosis, genetic inactivation of TNF- neither improved endothelial function nor normalized Nox2 expression or RONS production in TTP-/- animals. Systemic inflammation caused by TTP deficiency leads to endothelial dysfunction. This process is independent of cholesterol and not mediated by TNF- solely. Thus, other mediators, which need to be identified, contribute to enhanced cardiovascular risk in chronic inflammatory diseases. C1 [Bollmann, Franziska; Wu, Zhixiong; Siuda, Daniel; Xia, Ning; Henke, Jenny; Li, Huige; Kleinert, Hartmut; Pautz, Andrea] Johannes Gutenberg Univ Mainz, Univ Med Ctr, Dept Pharmacol, D-55131 Mainz, Germany. [Bollmann, Franziska; Siuda, Daniel] Johannes Gutenberg Univ Mainz, Univ Med Ctr, Ctr Thrombosis & Hemostasis, D-55131 Mainz, Germany. [Oelze, Matthias] Johannes Gutenberg Univ Mainz, Univ Med Ctr, Med Clin 2, D-55131 Mainz, Germany. [Stumpo, Deborah J.; Blackshear, Perry J.] NIEHS, Lab Signal Transduct, Res Triangle Pk, NC 27709 USA. RP Kleinert, H (reprint author), Johannes Gutenberg Univ Mainz, Univ Med Ctr, Dept Pharmacol, D-55131 Mainz, Germany. EM kleinert@mail.uni-mainz.de; pautz@uni-mainz.de RI Xia, Ning/P-3535-2015; Li, Huige/M-2662-2013 OI Li, Huige/0000-0003-3458-7391 FU Federal Ministry of Education and Research [BMBF 01EO1003]; Innovation Foundation of the State of Rhineland-Palatinate [961-386261/917K]; Deutsche Forschungsgemeinschaft [LI 1759/1-1] FX This work was supported by Federal Ministry of Education and Research Grant BMBF 01EO1003, Innovation Foundation of the State of Rhineland-Palatinate Grant 961-386261/917K, and Deutsche Forschungsgemeinschaft Grant LI 1759/1-1 (to H. K.). NR 70 TC 2 Z9 2 U1 0 U2 6 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 MAY 30 PY 2014 VL 289 IS 22 BP 15653 EP 15665 DI 10.1074/jbc.M114.566984 PG 13 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA AJ2DL UT WOS:000337465400047 PM 24727475 ER PT J AU Nakajima, T Sato, K Hanaoka, H Watanabe, R Harada, T Choyke, PL Kobayashi, H AF Nakajima, Takahito Sato, Kazuhide Hanaoka, Hirofumi Watanabe, Rira Harada, Toshiko Choyke, Peter L. Kobayashi, Hisataka TI The effects of conjugate and light dose on photo-immunotherapy induced cytotoxicity SO BMC CANCER LA English DT Article DE Photoimmunotherapy; Near infrared light; Light dose; Necrosis; Cytotoxicity ID NEAR-INFRARED PHOTOIMMUNOTHERAPY; CELLS IN-VITRO; FLUORESCENT PROTEINS; CELLULAR-DYNAMICS; UVC IRRADIATION; CANCER-CELLS; VIVO; EFFICACY; GFP; MICE AB Background: Photoimmunotherapy (PIT) is a highly cell-selective cancer therapy, which employs monoclonal antibodies conjugated to a potent photosensitizer (mAb-IR700). Once the conjugate has bound to the target cell, exposure to near infrared (NIR) light induces necrosis only in targeted cells with minimal damage to adjacent normal cells in vivo. Herein, we report on the effect of altering mAb-IR700 and light power and dose on effectiveness of PIT. Methods: For evaluating cytotoxicity, we employed ATP-dependent bioluminescence imaging using a luciferase-transfected MDA-MB-468luc cell line, which expresses EGFR and luciferase. In in vitro experiments, panitumumab-IR700 (Pan-IR700) concentration was varied in combination with varying NIR light doses administered by an LED at one of three power settings, 100 mA and 400 mA continuous wave and 1733 mA intermittent wave. For in vivo experiments, the MDA-MB-468luc orthotopic breast cancer was treated with varying doses of Pan-IR700 and light. Results: The in vitro cell study demonstrated that PIT induced cytotoxicity depended on light dose, when the conjugate concentration was kept constant. Increasing the dose of Pan-IR700 allowed lowering of the light dose to achieve equal effects thus indicating that for a given level of efficacy, the conjugate concentration multiplied by the light dose was a constant. A similar relationship between conjugate and light dose was observed in vivo. Conclusions: The efficacy of PIT is defined by the product of the number of bound antibody conjugates and the dose of NIR light and can be achieve equally with continuous and pulse wave LED light using different power densities. C1 [Nakajima, Takahito; Sato, Kazuhide; Hanaoka, Hirofumi; Watanabe, Rira; Harada, Toshiko; Choyke, Peter L.; Kobayashi, Hisataka] NCI, Mol Imaging Program, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. RP Kobayashi, H (reprint author), NCI, Mol Imaging Program, Ctr Canc Res, NIH, Bldg 10,Room B3B69,MSC 1088, Bethesda, MD 20892 USA. EM Kobayash@mail.nih.gov FU Intramural Research Program of the National Institutes of Health, National Cancer Institute, Center for Cancer Research FX This research was supported by the Intramural Research Program of the National Institutes of Health, National Cancer Institute, Center for Cancer Research. NR 15 TC 6 Z9 6 U1 1 U2 17 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 MAY 30 PY 2014 VL 14 AR 389 DI 10.1186/1471-2407-14-389 PG 7 WC Oncology SC Oncology GA AJ2ZF UT WOS:000337533500001 PM 24885589 ER PT J AU Cassetti, MC Halstead, SB AF Cassetti, M. Cristina Halstead, Scott B. TI Consultation on dengue vaccines: Progress in understanding protection, 26-28 June 2013, Rockville, Maryland SO VACCINE LA English DT Article DE Dengue; Dengue virus; Dengue hemorrhagic fever; Severe dengue; Vaccine; Immunopathogenesis; Acquired immunity; T cell immunity; Innate immunity ID IN-DEPTH ANALYSIS; VIRUS-INFECTION; HEMORRHAGIC-FEVER; ENVELOPE PROTEIN; THAI VILLAGES; TRANSMISSION; ANTIBODIES; IMMUNIZATION; PATHOGENESIS; CHILDREN AB There is an unmet need for a dengue vaccine to further prevent the spread of this disease and contain the growing pandemic. To this end several vaccine companies and academic groups are actively pursuing the development of a tetravalent vaccine to prevent dengue. In the last few years progress has been made in this area, including the first results of a vaccine efficacy trial and improved understanding of the immune responses to the infection. Despite this progress, development of dengue vaccines faces important challenges including the need for a vaccine that induces balanced immune responses against all dengue strains and an incomplete understanding of the mechanism(s) of protection against infection and disease. This is a summary of a Consultation on dengue vaccines held in June 26-28,2013 by the National Institute of Allergy and Infectious Diseases (part of the US National Institutes of Health) and the Dengue Vaccine Initiative (part of the International Vaccine Institute). The primary goal of this consultation was to review the progress in dengue vaccine development, evaluate the known mechanism of protection of dengue vaccines and discuss avenues for future research. C1 [Cassetti, M. Cristina] NIAID, NIH, Bethesda, MD 20892 USA. [Halstead, Scott B.] Int Vaccine Inst, Dengue Vaccine Initiat, Seoul, South Korea. RP Halstead, SB (reprint author), 5824 Edson Lane N, Bethesda, MD 20852 USA. EM halsteads@erols.com FU Sanofipasteur, Lyons, France, Takeda Pharmaceuticals, Chicago, Illinois, the Bill and Melinda Gates Foundation, Seattle, Washington [24050] FX This meeting received organizational support from the Henry M Jackson Foundation, Bethesda, Maryland and financial support from Sanofipasteur, Lyons, France, Takeda Pharmaceuticals, Chicago, Illinois, the Bill and Melinda Gates Foundation, Seattle, Washington (Contract # 24050) No grant numbers for sanofi or Takeda grants to the Jackson Foundation and the NIH Office of Rare Diseases. NR 39 TC 3 Z9 3 U1 0 U2 1 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0264-410X EI 1873-2518 J9 VACCINE JI Vaccine PD MAY 30 PY 2014 VL 32 IS 26 BP 3115 EP 3121 DI 10.1016/j.vaccine.2014.04.017 PG 7 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA AI4YL UT WOS:000336872500001 PM 24768502 ER PT J AU Maximova, OA Speicher, JM Skinner, JR Murphy, BR St Claire, MC Ragland, DR Herbertd, RL Pare, DR Moore, RM Pletnev, AG AF Maximova, Olga A. Speicher, James M. Skinner, Jeff R. Murphy, Brian R. St Claire, Marisa C. Ragland, Danny R. Herbertd, Richard L. Pare, Dan R. Moore, Rashida M. Pletnev, Alexander G. TI Assurance of neuroattenuation of a live vaccine against West Nile virus: A comprehensive study of neuropathogenesis after infection with chimeric WN/DEN4 Delta 30 vaccine in comparison to two parental viruses and a surrogate flavivirus reference vaccine SO VACCINE LA English DT Article DE West Nile virus (WNV); Live attenuated WNV vaccine; Neuropathogenesis; Neurovirulence; Nonhuman primates ID HEALTHY-ADULTS; UNITED-STATES; PRECLINICAL EVALUATION; NEUTRALIZING ANTIBODY; PROTECTIVE EFFICACY; RHESUS-MONKEYS; CLINICAL-TRIAL; PHASE-II; IMMUNOGENICITY; DISEASE AB The upsurge of West Nile virus (WNV) human infections in 2012 suggests that the US can expect periodic WNV outbreaks in the future. Availability of safe and effective vaccines against WNV in endemic areas, particularly for aging populations that are at high risk of West Nile neuroinvasive disease (WNND), could be beneficial. WN/DEN4 Delta 30 is a live, attenuated chimeric vaccine against WNV produced by replacement of the genes encoding the pre-membrane and envelope protein genes of the vaccine virus against dengue virus type 4 (DEN4 Delta 30) with corresponding sequences derived from a wild type WNV. Following intrathalamic inoculation of nonhuman primates (NHPs), a comprehensive neuropathogenesis study was performed and neurovirulence of WN/DEN4 Delta 30 vaccine candidate was compared to that of two parental viruses (i.e., WNV and DEN4 Delta 30), as well as to that of an attenuated flavivirus surrogate reference (i.e., yellow fever YF 17D). Clinical and virological data, as well as results of a semi-quantitative histopathological analysis, demonstrated that WN/DEN4 Delta 30 vaccine is highly attenuated for the central nervous system (CNS) of NHPs in comparison to a wild type WNV. Importantly, based on the virus replicative ability in the CNS of NHPs and the degree of induced histopathological changes, the level of neuroattenuation of WN/DEN4 Delta 30 vaccine was similar to that of YF 17D, and therefore within an acceptable range. In addition, we show that the DEN4 Delta 30 vaccine tested in this study also has a low neurovirulence profile. In summary, our results demonstrate a high level of neuroattenuation of two vaccine candidates, WN/DEN4 Delta 30 and DEN4 Delta 30. We also show here a remarkable sensitivity of our WNV-NY99 NHP model, as well as striking resemblance of the observed neuropathology to that seen in human WNND. These results support the use of this NHP model for translational studies of WNV neuropathogenesis and/or testing the effectiveness of vaccines and therapeutic approaches. Published by Elsevier Ltd. C1 [Maximova, Olga A.; Speicher, James M.; Murphy, Brian R.; Pletnev, Alexander G.] NIAID, Infect Dis Lab, NIH, Bethesda, MD 20892 USA. [Skinner, Jeff R.] NIAID, Bioinformat & Computat Biosci Branch, NIH, Bethesda, MD 20892 USA. [St Claire, Marisa C.; Ragland, Danny R.] NIAID, Off Chief Scientist, Integrated Res Facil, NIH, Frederick, MD 21702 USA. [Herbertd, Richard L.; Pare, Dan R.; Moore, Rashida M.] NIAID, Comparat Med Branch, NIH, Bethesda, MD 20892 USA. RP Maximova, OA (reprint author), NIAID, Infect Dis Lab, NIH, 33 North Dr, Bethesda, MD 20892 USA. EM maximovao@niaid.nih.gov; apletnev@niaid.nih.gov FU NIAID Intramural Research Program FX We acknowledge Lawrence Faucette, Marina Rahman, Katherine Shea, Marsha Abramson, Sarah Rovezzi, Dr. Robin Kastenmayer, and Dr. William Elkins (Comparative Medicine Branch, NIAID, NIH), Russell Byrum (Integrated Research Facility, NIAID, NIH), Dr. Dzung Thach and Anthony Gresko (Laboratory of Infectious Diseases, NIAID, NIH), and Dr. Shari Price-Schiavi and the staff of the Pathology Associates Division of Charles River Laboratories (Frederick, MD) for their most valuable help with animal experiments and excellent technical support. We also thank Dr. Jeffrey Cohen, Dr. Jeffrey Taubenberger, and Dr. Stephen Whitehead (Laboratory of Infectious Diseases, NIAID, NIH) for their support, helpful discussions and critical reading of the manuscript. This work was supported by funds provided by the NIAID Intramural Research Program. NR 49 TC 4 Z9 4 U1 0 U2 4 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0264-410X EI 1873-2518 J9 VACCINE JI Vaccine PD MAY 30 PY 2014 VL 32 IS 26 BP 3187 EP 3197 DI 10.1016/j.vaccine.2014.04.002 PG 11 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA AI4YL UT WOS:000336872500012 PM 24736001 ER PT J AU Donahue, RN Duncan, BB Fry, TJ Jones, B Bachovchin, WW Kiritsy, CP Lai, JH Wu, WG Zhao, P Liu, YX Tsang, KY Hodge, JW AF Donahue, Renee N. Duncan, Brynn B. Fry, Terry J. Jones, Barry Bachovchin, William W. Kiritsy, Christopher P. Lai, Jack H. Wu, Wengen Zhao, Peng Liu, Yuxin Tsang, Kwong-Yok Hodge, James W. TI A pan inhibitor of DASH family enzymes induces immunogenic modulation and sensitizes murine and human carcinoma cells to antigen-specific cytotoxic T lymphocyte killing: implications for combination therapy with cancer vaccines SO VACCINE LA English DT Article DE Immunogenic modulation; T-cell response; DASH family enzymes; Immunotherapy; Vaccine ID DIPEPTIDYL-PEPTIDASE-IV; ANTITUMOR RESPONSES; CHEMOTHERAPY; EXPRESSION; POTENT; IMMUNOTHERAPY; IRRADIATION; VACCINATION; GENERATION; TALABOSTAT AB Recent studies have suggested that pan inhibitors of dipeptidyl peptidase-4 activity and/or structure homologs (DASH), including ARI-4175, can mediate tumor regression by immune-mediated mechanisms. This study assessed the potential of combining ARI-4175 with cancer vaccines. We evaluated ARI-4175's effect on immunogenic modulation, ability to sensitize tumor cells to antigen-specific CTL killing, effect on immune-cell subsets and function, and antitumor activity in 2 tumor models, both as a monotherapy and in combination with a recombinant viral or dendritic cell (DC)-based tumor-cell vaccine. ARI-4175's effects on the growth, surface phenotype, and antigen-specific CTL-mediated lysis of murine and human carcinoma cell lines were assessed in vitro. In vivo, C57BL-6 mice were treated orally with ARI-4175, after which splenocytes were assessed by flow cytometry and functional assays. Antitumor studies were performed in murine models of colon carcinoma (MC38-CEA(+) in CEA-transgenic C57BL6 mice) and rhabdomyosarcoma (M3-9-M in C57BL-6 mice). Mice received oral ARI-4175 alone or in combination with a vaccine consisting of recombinant vaccinia/fowlpox CEA-TRICOM (colon model) or a DC-based tumor-cell vaccine (rhabdomyosarcoma model). Exposure to ARI-4175 had no effect on the proliferation or viability of carcinoma cells in vitro; however, it did alter tumor phenotype, making murine and human tumor cells more sensitive to antigen-specific CTL killing. Assessment of immune-cell subsets and function indicated that ARI-4175 increased levels of natural killer cells and DCs. Detrimental immune effects, including reduced T effector cells and increased immunosuppressive cells (Tregs, MDSCs), were normalized when treatment stopped, suggesting that scheduling is critical when combining this agent with vaccine. As a monotherapy, ARI-4175 had potent antitumor activity in both tumor models, and had even greater effects when combined with a vaccine (either DC-based or poxviral vector based). These findings provide the rationale for the combined use of cancer immunotherapy with DASH enzyme inhibitors such as ARI-4175. Published by Elsevier Ltd. C1 [Donahue, Renee N.; Tsang, Kwong-Yok; Hodge, James W.] NCI, Lab Tumor Immunol & Biol, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. [Duncan, Brynn B.; Fry, Terry J.] NCI, Pediat Oncol Branch, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. [Jones, Barry; Bachovchin, William W.; Lai, Jack H.; Wu, Wengen; Zhao, Peng; Liu, Yuxin] Tufts Univ, Sch Med, Dept Biochem, Boston, MA 02111 USA. [Bachovchin, William W.; Kiritsy, Christopher P.; Lai, Jack H.] Arisaph Pharmaceut, Boston, MA USA. RP Hodge, JW (reprint author), NCI, Lab Tumor Immunol & Biol, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. EM renee.donahue@nih.gov; bbd6@georgetown.edu; fryt@mail.nih.gov; Barry.jones@tufts.edu; william.bachoychin@tufts.edu; ckiritsy@arisaph.com; Jack.Lai@tufts.edu; Wengen.Wu@tufts.edu; Peng.Zhao@tufts.edu; Yu.Liu@tufts.edu; tsangkwo@mail.nih.gov; hodgej@mail.nih.gov RI Hodge, James/D-5518-2015 OI Hodge, James/0000-0001-5282-3154 FU Intramural Research Program of the Center for Cancer Research; National Cancer Institute; Intramural Program, National Institutes of Health FX This research was supported by the Intramural Research Program of the Center for Cancer Research, National Cancer Institute, Intramural Program, National Institutes of Health. NR 33 TC 3 Z9 3 U1 0 U2 10 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0264-410X EI 1873-2518 J9 VACCINE JI Vaccine PD MAY 30 PY 2014 VL 32 IS 26 BP 3223 EP 3231 DI 10.1016/j.vaccine.2014.04.008 PG 9 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA AI4YL UT WOS:000336872500017 PM 24731809 ER PT J AU Sagar, D Masih, S Schell, T Jacobson, S Comber, JD Philip, R Wigdahl, B Jain, P Khan, ZK AF Sagar, Divya Masih, Shet Schell, Todd Jacobson, Steven Comber, Joseph D. Philip, Ramila Wigdahl, Brian Jain, Pooja Khan, Zafar K. TI In vivo immunogenicity of Tax(11-19) epitope in HLA-A2/DTR transgenic mice: Implication for dendritic cell-based anti-HTLV-1 vaccine SO VACCINE LA English DT Article DE HTLV-1; Tax; Dendritic cells; HLA-A2.1 transgenic mice; CD11c-DTR transgenic mice ID VIRUS TYPE-I; CD8(+) T-CELLS; MURINE LEUKEMIA-VIRUS; MYELIN BASIC-PROTEIN; TOLERANCE INDUCTION; TAX PROTEIN; TYPE-1 TAX; HTLV-I; AUTOIMMUNE ENCEPHALOMYELITIS; NEUROLOGICAL DISEASE AB Viral oncoprotein Tax plays key roles in transformation of human T-cell leukemia virus (HTLV-1)-infected T cells leading to adult T-cell leukemia (ATL), and is the key antigen recognized during HTLV-associated myelopathy (HAM). In HLA-A2+ asymptomatic carriers as well as ATL and HAM patients, Tax(11-19) epitope exhibits immunodominance. Here, we evaluate CD8 T-cell immune response against this epitope in the presence and absence of dendritic cells (DCs) given the recent encouraging observations made with Phase 1 DC-based vaccine trial for ATL. To facilitate these studies, we first generated an HLA-A2/DTR hybrid mouse strain carrying the HLA-A2.1 and CD11c-DTR genes. We then studied CD8 T-cell immune response against Tax(11-19) epitope delivered in the absence or presence of Freund's adjuvant and/or DCs. Overall results demonstrate that naturally presented Tax epitope could initiate an antigen-specific CD8T cell response in vivo but failed to do so upon DC depletion. Presence of adjuvant potentiated Tax(11-19)-specific response. Elevated serum IL-6 levels coincided with depletion of DCs whereas decreased TGF-beta was associated with adjuvant use. Thus, Tax(11-19) epitope is a potential candidate for the DC-based anti-HTLV-1 vaccine and the newly hybrid mouse strain could be used for investigating DC involvement in human class-I-restricted immune responses. (C) 2014 Elsevier Ltd. All rights reserved. C1 [Sagar, Divya; Masih, Shet; Jain, Pooja; Khan, Zafar K.] Drexel Univ, Coll Med, Dept Microbiol & Immunol, Drexel Inst Biotechnol & Virol Res, Philadelphia, PA 19104 USA. [Schell, Todd] Penn State Univ, Coll Med, Dept Microbiol & Immunol, Hershey, PA USA. [Jacobson, Steven] NIH, Viral Immunol Sect, Neuroimmunol Branch, Bethesda, MD 20892 USA. [Comber, Joseph D.; Philip, Ramila] Immunotope Inc, Doylestown, PA USA. [Wigdahl, Brian] Drexel Univ, Coll Med, Dept Microbiol & Immunol, Philadelphia, PA 19104 USA. [Wigdahl, Brian] Drexel Univ, Coll Med, Inst Mol Med & Infect Dis, Ctr Mol Virol & Translat Neurosci, Philadelphia, PA 19104 USA. RP Jain, P (reprint author), Drexel Univ, Coll Med, Drexel Inst Biotechnol & Virol Res, Dept Microbiol & Immunol, 3805 Old Easton Rd, Doylestown, PA 18902 USA. EM pooja.jain@drexelmed.edu; zkhan@drexelmed.edu OI Masih, Shet/0000-0003-1920-476X; Philip, Ramila/0000-0003-1530-7665 FU Public Health Service, National Institutes of Health [NIAID R21 AI093172-01]; NIAID [R01 AI077414]; NCI [R01] FX This work was supported by the Public Health Service, National Institutes of Health, grant NIAID R21 AI093172-01 to ZKK. Supports through NIAID R01 AI077414 to PJ and NCI R01 to BW/PJ are also acknowledged. We also wish to acknowledge the kind gift of SP2/0 transfectants secreting mouse recombinant Flt-3L from Dr. Robert Rottapel, Ontario Cancer Institute, Toronto, Canada. Both strains of mice were purchased from Jackson Laboratories, which helped in obtaining permission to cross-breed from the original source of these mice and requested acknowledgment of Dr. Dan Littman for B6.FVB-Tg Itgax-DTR/EGFP 57Lan/J (CD11c-DTR) mice. NR 65 TC 0 Z9 0 U1 0 U2 3 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0264-410X EI 1873-2518 J9 VACCINE JI Vaccine PD MAY 30 PY 2014 VL 32 IS 26 BP 3274 EP 3284 DI 10.1016/j.vaccine.2014.03.087 PG 11 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA AI4YL UT WOS:000336872500024 PM 24739247 ER PT J AU Massart, R Suderman, M Provencal, N Yi, C Bennett, AJ Suomi, S Szyf, M AF Massart, R. Suderman, M. Provencal, N. Yi, C. Bennett, A. J. Suomi, S. Szyf, M. TI HYDROXYMETHYLATION AND DNA METHYLATION PROFILES IN THE PREFRONTAL CORTEX OF THE NON-HUMAN PRIMATE RHESUS MACAQUE AND THE IMPACT OF MATERNAL DEPRIVATION ON HYDROXYMETHYLATION SO NEUROSCIENCE LA English DT Article DE monkeys; hydroxymethylation; brain; early-adversity; rearing; maternal deprivation ID EMBRYONIC STEM-CELLS; EARLY-LIFE STRESS; EPIGENETIC REGULATION; EARLY EXPERIENCE; BASE-RESOLUTION; GENE-EXPRESSION; THYMINE DNA; HUMAN BRAIN; 5-HYDROXYMETHYLCYTOSINE; ENVIRONMENT AB 5-Hydroxymethylcytosine (5hmC) is abundant in the brain, suggesting an important role in epigenetic control of neuronal functions. In this paper, we show that 5hmC and 5-methylcytosine (5mC) levels are coordinately distributed in gene promoters of the rhesus macaque prefrontal cortex. Although promoter hydroxymethylation and methylation are overall negatively correlated with expression, a subset of highly expressed genes involved in specific cerebral functions is associated with high levels of 5mC and 5hmC. These relationships were also observed in the mouse cortex. Furthermore, we found that early-life maternal deprivation is associated, in the adult monkey cortex, with DNA hydroxymethylation changes of promoters of genes related to neurological functions and psychological disorders. These results reveal that early social adversity triggers variations in brain DNA hydroxymethylation that could be detected in adulthood. (C) 2014 IBRO. Published by Elsevier Ltd. All rights reserved. C1 [Massart, R.; Suderman, M.; Provencal, N.; Yi, C.; Szyf, M.] McGill Univ, Dept Pharmacol & Therapeut, Montreal, PQ H3G 1Y6, Canada. [Provencal, N.; Szyf, M.] McGill Univ, Sackler Program Epigenet & Dev Psychobiol, Montreal, PQ H3G 1Y6, Canada. [Provencal, N.] Univ Montreal, Res Unit Childrens Psychosocial Maladjustment, Montreal, PQ H3T 1C5, Canada. [Provencal, N.] Univ Montreal, St Justine Hosp, Res Ctr, Montreal, PQ H3T 1C5, Canada. [Bennett, A. J.; Suomi, S.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Comparat Ethol Lab, NIH, Bethesda, MD 20892 USA. [Bennett, A. J.] Univ Wisconsin, Dept Psychol, Madison, WI 53715 USA. [Bennett, A. J.] Univ Wisconsin, Harlow Ctr Biol Psychol, Madison, WI 53715 USA. RP Suomi, S (reprint author), Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Comparat Ethol Lab, NIH, DHHS, Bethesda, MD 20892 USA. EM suomis@lce.nichd.nih.gov; moshe.szyf@mcgill.ca FU Canadian Institute of Health Research (CIHR); Sackler Program in Psychobiology and Epigenetics at McGill University; European Research Area-Neuron Network (ERA-NET NEURON); Division of Intramural Research, Eunice Kennedy Shriver National Institutes of Child Health and Human Development (NICHD), National Institutes of Health (NIH) FX Supported by a grant from the Canadian Institute of Health Research (CIHR) to M. S. and the Sackler Program in Psychobiology and Epigenetics at McGill University to MS and a grant from the European Research Area-Neuron Network (ERA-NET NEURON) to M. S. and by funds from the Division of Intramural Research, Eunice Kennedy Shriver National Institutes of Child Health and Human Development (NICHD), National Institutes of Health (NIH). S. S. is a fellow of the Canadian Institute for Advanced Research. We would like to thank Claire Guillemin, Angela Ruggiero, Dongsha Wang, Peter J. Pierre, David P. Friedman for their technical assistance and discussions. The authors declare no conflict of interest. NR 64 TC 18 Z9 19 U1 0 U2 10 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 MAY 30 PY 2014 VL 268 BP 139 EP 148 DI 10.1016/j.neuroscience.2014.03.021 PG 10 WC Neurosciences SC Neurosciences & Neurology GA AG6AX UT WOS:000335501900013 PM 24657458 ER PT J AU Lee, JE Ge, K AF Lee, Ji-Eun Ge, Kai TI Transcriptional and epigenetic regulation of PPAR gamma expression during adipogenesis SO CELL AND BIOSCIENCE LA English DT Review DE PPAR gamma; Adipogenesis; Transcriptional regulation; Enhancer; Epigenetic regulation; Histone acetylation; Histone methylation; Chromatin remodeling ID ACTIVATED-RECEPTOR-GAMMA; FAMILIAL PARTIAL LIPODYSTROPHY; LYSINE-4 METHYLTRANSFERASE COMPLEX; ADIPOCYTE DIFFERENTIATION; HISTONE H3; C/EBP-ALPHA; BINDING-PROTEINS; GENOME-WIDE; IN-VIVO; CELL DIFFERENTIATION AB The nuclear receptor PPAR gamma is a master regulator of adipogenesis. PPAR gamma is highly expressed in adipose tissues and its expression is markedly induced during adipogenesis. In this review, we describe the current knowledge, as well as future directions, on transcriptional and epigenetic regulation of PPAR gamma expression during adipogenesis. Investigating the molecular mechanisms that control PPAR gamma expression during adipogenesis is critical for understanding the development of white and brown adipose tissues, as well as pathological conditions such as obesity and diabetes. The robust induction of PPAR gamma expression during adipogenesis also serves as an excellent model system for studying transcriptional and epigenetic regulation of cell-type-specific gene expression. C1 [Lee, Ji-Eun; Ge, Kai] NIDDK, Adipocyte Biol & Gene Regulat Sect, Lab Endocrinol & Receptor Biol, NIH, Bethesda, MD 20892 USA. RP Ge, K (reprint author), NIDDK, Adipocyte Biol & Gene Regulat Sect, Lab Endocrinol & Receptor Biol, NIH, Bethesda, MD 20892 USA. EM kaig@niddk.nih.gov RI Lee, Ji-Eun/F-7891-2011 OI Lee, Ji-Eun/0000-0002-3768-7016 NR 104 TC 27 Z9 27 U1 7 U2 32 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 2045-3701 J9 CELL BIOSCI JI Cell Biosci. PD MAY 29 PY 2014 VL 4 AR 29 DI 10.1186/2045-3701-4-29 PG 11 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA AJ0BK UT WOS:000337313800001 PM 24904744 ER PT J AU Robinson, TP Wint, GRW Conchedda, G Van Boeckel, TP Ercoli, V Palamara, E Cinardi, G D'Aietti, L Hay, SI Gilbert, M AF Robinson, Timothy P. Wint, G. R. William Conchedda, Giulia Van Boeckel, Thomas P. Ercoli, Valentina Palamara, Elisa Cinardi, Giuseppina D'Aietti, Laura Hay, Simon I. Gilbert, Marius TI Mapping the Global Distribution of Livestock SO PLOS ONE LA English DT Article ID AVIAN INFLUENZA; DOMESTIC DUCKS; CLIMATE-CHANGE; LAND-COVER; AFRICA; SYSTEMS; ASIA; TRYPANOSOMOSIS; DYNAMICS; THAILAND AB Livestock contributes directly to the livelihoods and food security of almost a billion people and affects the diet and health of many more. With estimated standing populations of 1.43 billion cattle, 1.87 billion sheep and goats, 0.98 billion pigs, and 19.60 billion chickens, reliable and accessible information on the distribution and abundance of livestock is needed for a many reasons. These include analyses of the social and economic aspects of the livestock sector; the environmental impacts of livestock such as the production and management of waste, greenhouse gas emissions and livestock-related land-use change; and large-scale public health and epidemiological investigations. The Gridded Livestock of the World (GLW) database, produced in 2007, provided modelled livestock densities of the world, adjusted to match official (FAOSTAT) national estimates for the reference year 2005, at a spatial resolution of 3 minutes of arc (about 5x5 km at the equator). Recent methodological improvements have significantly enhanced these distributions: more up-to date and detailed sub-national livestock statistics have been collected; a new, higher resolution set of predictor variables is used; and the analytical procedure has been revised and extended to include a more systematic assessment of model accuracy and the representation of uncertainties associated with the predictions. This paper describes the current approach in detail and presents new global distribution maps at 1 km resolution for cattle, pigs and chickens, and a partial distribution map for ducks. These digital layers are made publically available via the Livestock Geo-Wiki (http://www.livestock.geo-wiki.org), as will be the maps of other livestock types as they are produced. C1 [Robinson, Timothy P.] ILRI, Livestock Syst & Environm Res Theme LSE, Nairobi, Kenya. [Robinson, Timothy P.; Conchedda, Giulia; Ercoli, Valentina; Palamara, Elisa; Cinardi, Giuseppina; D'Aietti, Laura] Food & Agr Org United Nations FAO, Anim Prod & Hlth Div AGA, Rome, Italy. [Wint, G. R. William] Univ Oxford, Dept Zool, ERGO, Oxford OX1 3PS, England. [Van Boeckel, Thomas P.; Gilbert, Marius] Univ Libre Brussels, Brussels, Belgium. [Van Boeckel, Thomas P.; Gilbert, Marius] Fonds Natl Rech Sci, Brussels, Belgium. [Van Boeckel, Thomas P.] Princeton Univ, Dept Biol, Dept Ecol & Evolutionary, Princeton, NJ 08544 USA. [Van Boeckel, Thomas P.] Princeton Environm Inst, Princeton, NJ USA. [Hay, Simon I.] Univ Oxford, Dept Zool, Spatial Ecol & Epidemiol Grp, Oxford OX1 3PS, England. [Hay, Simon I.] NIH, Fogarty Int Ctr, Bethesda, MD 20892 USA. RP Robinson, TP (reprint author), ILRI, Livestock Syst & Environm Res Theme LSE, Nairobi, Kenya. EM t.robinson@cgiar.org RI Hay, Simon/F-8967-2015; OI Hay, Simon/0000-0002-0611-7272; Gilbert, Marius/0000-0003-3708-3359 FU Consultative Group on International Agricultural Research (CGIAR) Research Programmes: Humidtropics; Climate Change, Agriculture and Food Security (CCAFS); Agriculture for Nutrition and Health (A4NH); 'Fonds National de la Recherche Scientifique' (FNRS); Wellcome Trust [095066]; Li Ka Shing Foundation; Research and Policy for Infectious Disease Dynamics (RAPIDD) program of the Science & Technology Directorate, Department of Homeland Security; Fogarty International Center (FIC); Animal Production and Health Division (AGA) of the Food and Agriculture Organization (FAO) of the United Nations: in particular the UK Department for International Development (DFID); USAID; United States NIH FIC grant [3R01TW007869-03, 1R56TW009502-01]; FNRS Projet de Recherche (PDR) [T.0073.13]; National Institutes of Health (NIH) FX TPR is funded by the following Consultative Group on International Agricultural Research (CGIAR) Research Programmes: Humidtropics; Climate Change, Agriculture and Food Security (CCAFS); and Agriculture for Nutrition and Health (A4NH). MG & TPVB are funded by the 'Fonds National de la Recherche Scientifique' (FNRS). SIH is funded by a Senior Research Fellowship from the Wellcome Trust (#095066) and receives support from the Li Ka Shing Foundation. SIH also acknowledges funding support from the Research and Policy for Infectious Disease Dynamics (RAPIDD) program of the Science & Technology Directorate, Department of Homeland Security, and the Fogarty International Center (FIC), National Institutes of Health (NIH). The bulk of this work was funded through various programmes and projects within the Animal Production and Health Division (AGA) of the Food and Agriculture Organization (FAO) of the United Nations: in particular the UK Department for International Development (DFID)-funded Pro-Poor Livestock Policy Initiative and the USAID-funded Emerging Pandemic Threats Plus (EPT+) programme. Other contributors include the United States NIH FIC grants: 3R01TW007869-03 and 1R56TW009502-01 and the FNRS Projet de Recherche (PDR) T.0073.13. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 65 TC 62 Z9 63 U1 13 U2 78 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 MAY 29 PY 2014 VL 9 IS 5 AR e96084 DI 10.1371/journal.pone.0096084 PG 13 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA AI3UR UT WOS:000336790800001 PM 24875496 ER PT J AU Li, MX Volker, J Breslauer, KJ Wilson, DM AF Li, Mengxia Voelker, Jens Breslauer, Kenneth J. Wilson, David M., III TI APE1 Incision Activity at Abasic Sites in Tandem Repeat Sequences SO JOURNAL OF MOLECULAR BIOLOGY LA English DT Article DE APEX1; AP or abasic site; tandem repeat; telomere; trinucleotide expansion ID BASE EXCISION-REPAIR; HUMAN APURINIC ENDONUCLEASE; EQUILIBRIUM MELTING CURVES; URACIL-DNA GLYCOSYLASE; REPLICATION PROTEIN-A; CELL NUCLEAR ANTIGEN; BULGE LOOPS; APURINIC/APYRIMIDINIC ENDONUCLEASE; NUCLEOTIDE-SEQUENCE; THERMODYNAMIC DATA AB Repetitive DNA sequences, such as those present in microsatellites and minisatellites, telomeres, and trinucleotide repeats (linked to fragile X syndrome, Huntington disease, etc.), account for nearly 30% of the human genome. These domains exhibit enhanced susceptibility to oxidative attack to yield base modifications, strand breaks, and abasic sites; have a propensity to adopt non-canonical DNA forms modulated by the positions of the lesions; and, when not properly processed, can contribute to genome instability that underlies aging and disease development. Knowledge on the repair efficiencies of DNA damage within such repetitive sequences is therefore crucial for understanding the impact of such domains on genomic integrity. In the present study, using strategically designed oligonucleotide substrates, we determined the ability of human apurinic/apyrimidinic endonuclease 1 (APE1) to cleave at apurinic/apyrimidinic (AP) sites in a collection of tandem DNA repeat landscapes involving telomeric and CAG/CTG repeat sequences. Our studies reveal the differential influence of domain sequence, conformation, and AP site location/relative positioning on the efficiency of APE1 binding and strand incision. Intriguingly, our data demonstrate that APE1 endonuclease efficiency correlates with the thermodynamic stability of the DNA substrate. We discuss how these results have both predictive and mechanistic consequences for understanding the success and failure of repair protein activity associated with such oxidatively sensitive, conformationally plastic/dynamic repetitive DNA domains. Published by Elsevier Ltd. C1 [Li, Mengxia; Wilson, David M., III] NIA, Lab Mol Gerontol, Intramural Res Program, NIH, Baltimore, MD 21224 USA. [Voelker, Jens; Breslauer, Kenneth J.] Rutgers State Univ, Dept Chem & Chem Biol, Piscataway, NJ 08854 USA. [Breslauer, Kenneth J.] Rutgers Canc Inst New Jersey, New Brunswick, NJ 08901 USA. RP Wilson, DM (reprint author), NIA, Lab Mol Gerontol, Intramural Res Program, NIH, 251 Bayview Blvd, Baltimore, MD 21224 USA. EM wilsonda@mail.nih.gov FU Intramural Research Program at the National Institutes of Health, National Institute on Aging; National Institutes of Health [GM23509, GM34469, CA47995] FX We wish to thank Dr. Yie Liu (National Institute on Aging) and Dr. G. Eric Plum (IBET Inc., Columbus, OH) for their constructive comments on the manuscript. This research was supported by the Intramural Research Program at the National Institutes of Health, National Institute on Aging, and National Institutes of Health grants GM23509, GM34469, and CA47995 (to K.J.B.). NR 62 TC 5 Z9 6 U1 1 U2 5 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 MAY 29 PY 2014 VL 426 IS 11 BP 2183 EP 2198 DI 10.1016/j.jmb.2014.03.014 PG 16 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA AI2PA UT WOS:000336699300004 PM 24703901 ER PT J AU Volkow, ND Frieden, TR Hyde, PS Cha, SS AF Volkow, Nora D. Frieden, Thomas R. Hyde, Pamela S. Cha, Stephen S. TI Medication-Assisted Therapies - Tackling the Opioid-Overdose Epidemic SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Editorial Material ID DEATHS C1 [Volkow, Nora D.] NIDA, NIH, Bethesda, MD 20892 USA. [Hyde, Pamela S.] Subst Abuse & Mental Hlth Serv Adm, Rockville, MD USA. [Cha, Stephen S.] Ctr Medicare Serv, Ctr Medicaid & CHIP Serv, Baltimore, MD USA. [Cha, Stephen S.] Ctr Medicaid Serv, Ctr Medicaid & CHIP Serv, Baltimore, MD USA. [Frieden, Thomas R.] Ctr Dis Control & Prevent, Atlanta, GA USA. RP Volkow, ND (reprint author), NIDA, NIH, Bethesda, MD 20892 USA. NR 5 TC 133 Z9 133 U1 3 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 MAY 29 PY 2014 VL 370 IS 22 BP 2063 EP 2066 DI 10.1056/NEJMp1402780 PG 4 WC Medicine, General & Internal SC General & Internal Medicine GA AH9BM UT WOS:000336434000003 PM 24758595 ER PT J AU Padmakumar, VC Masiuk, KE Luger, D Lee, C Coppola, V Tessarollo, L Hoover, SB Karavanova, I Buonanno, A Simpson, RM Yuspa, SH AF Padmakumar, V. C. Masiuk, Katelyn E. Luger, Dror Lee, Christina Coppola, Vincenzo Tessarollo, Lino Hoover, Shelley B. Karavanova, Irina Buonanno, Andres Simpson, R. Mark Yuspa, Stuart H. TI Detection of differential fetal and adult expression of chloride intracellular channel 4 (CLIC4) protein by analysis of a green fluorescent protein knock-in mouse line SO BMC DEVELOPMENTAL BIOLOGY LA English DT Article DE CLIC4; GFP knockin; Fetal brain; Adult brain; Kidney function ID DENSE-CORE VESICLES; GENE-EXPRESSION; MOLECULAR-CLONING; NUCLEAR TRANSLOCATION; ION CHANNEL; CL-CHANNEL; RAT-BRAIN; CELLS; FAMILY; P64H1 AB Background: Chloride Intracellular Channel 4 (CLIC4) is one of seven members in the closely related CLIC protein family. CLIC4 is involved in multiple cellular processes including apoptosis, cellular differentiation, inflammation and endothelial tubulogenesis. Despite over a decade of research, no comprehensive in situ expression analysis of CLIC4 in a living organism has been reported. In order to fulfill this goal, we generated a knock-in mouse to express Green Fluorescent Protein (GFP) from the CLIC4 locus, thus substituting the GFP coding region for CLIC4. We used GFP protein expression to eliminate cross reaction with other CLIC family members. Results: We analyzed CLIC4 expression during embryonic development and adult organs. During mid and late gestation, CLIC4 expression is modulated particularly in fetal brain, heart, thymus, liver and kidney as well as in developing brown adipose tissue and stratifying epidermis. In the adult mouse, CLIC4 is highly expressed globally in vascular endothelial cells as well as in liver, lung alveolar septae, pancreatic acini, spermatogonia, renal proximal tubules, cardiomyocytes and thymic epithelial cells. Neural expression included axonal tracks, olfactory bulb, Purkinje cell layer and dentate gyrus. Renal CLIC4 expression was most pronounced in proximal tubules, although altered renal function was not detected in the absence of CLIC4. Myeloid cells and B cells of the spleen are rich in CLIC4 expression as are CD4 and CD8 positive T cells. Conclusions: In a comprehensive study detailing CLIC4 expression in situ in a mouse model that excludes cross reaction with other family members, we were able to document previously unreported expression for CLIC4 in developing fetus, particularly the brain. In addition, compartmentalized expression of CLIC4 in specific adult tissues and cells provides a focus to explore potential functions of this protein not addressed previously. C1 [Padmakumar, V. C.; Masiuk, Katelyn E.; Luger, Dror; Lee, Christina; Hoover, Shelley B.; Simpson, R. Mark; Yuspa, Stuart H.] NCI, Lab Canc Biol & Genet, Bethesda, MD 20892 USA. [Karavanova, Irina; Buonanno, Andres] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Mol Neurobiol Sect, Bethesda, MD USA. [Coppola, Vincenzo; Tessarollo, Lino] NCI, Mouse Canc Genet Program, Frederick, MD 21701 USA. [Yuspa, Stuart H.] NCI, NIH, Bethesda, MD 20892 USA. RP Yuspa, SH (reprint author), NCI, Lab Canc Biol & Genet, Bethesda, MD 20892 USA. EM yuspas@mail.nih.gov OI Coppola, Vincenzo/0000-0001-6163-1779 FU Intramural Research Program of the Center for Cancer Research; National Cancer Institute; National Institute on Minority Health and Health Disparities FX This work was supported by the Intramural Research Program of the Center for Cancer Research, National Cancer Institute and National Institute on Minority Health and Health Disparities. NR 48 TC 6 Z9 6 U1 1 U2 6 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1471-213X J9 BMC DEV BIOL JI BMC Dev. Biol. PD MAY 28 PY 2014 VL 14 AR 24 DI 10.1186/1471-213X-14-24 PG 17 WC Developmental Biology SC Developmental Biology GA AK7DU UT WOS:000338587300001 PM 24886590 ER PT J AU Cruz, FC Babin, KR Leao, RM Goldart, EM Bossert, JM Shaham, Y Hope, BT AF Cruz, Fabio C. Babin, Klil R. Leao, Rodrigo M. Goldart, Evan M. Bossert, Jennifer M. Shaham, Yavin Hope, Bruce T. TI Role of Nucleus Accumbens Shell Neuronal Ensembles in Context-Induced Reinstatement of Cocaine-Seeking SO JOURNAL OF NEUROSCIENCE LA English DT Article DE conditioned cues; Daun02 inactivation; drug environment; extinction; Fos; self-administration ID MEDIAL PREFRONTAL CORTEX; C-FOS IMMUNOREACTIVITY; INDUCED RELAPSE; HEROIN SEEKING; DRUG SEEKING; GLUTAMATE RECEPTORS; BASAL GANGLIA; RATS; STRIATUM; CORE AB Environmental contexts previously associated with drug use provoke relapse to drug use in humans and reinstatement of drug seeking in animal models of drug relapse. We examined whether context-induced reinstatement of cocaine seeking is mediated by activation of context-selected nucleus accumbens neurons. We trained rats to self-administer cocaine in Context A and extinguished their lever-pressing in a distinct Context B. On test day, reexposure to the cocaine-associated Context A reinstated cocaine seeking and increased expression of the neural activity marker Fos in 3.3% of accumbens shell and 1.6% of accumbens core neurons. To assess a causal role for these activated neurons, we used the Daun02 inactivation procedure to selectively inactivate these neurons. We trained c-fos-lacZ transgenic rats to self-administer cocaine in Context A and extinguished their lever-pressing in Context B. On induction day, we exposed rats to either Context A or a novel Context C for 30 min and injected Daun02 or vehicle into accumbens shell or core 60 min later. On test day, 3 d after induction day, the ability of Context A to reinstate cocaine seeking and increase neuronal activity in accumbens shell was attenuated when Daun02 was previously injected after exposure to Context A. Daun02 injections after exposure to the novel Context C had no effect on context-induced reinstatement of cocaine seeking despite much greater numbers of Fos-expressing neurons induced by Context C. Daun02 injections in accumbens core had no effect. Our data suggest that context-induced reinstatement of cocaine seeking is mediated by activation of context-selected accumbens shell but not core neuronal ensembles. C1 [Cruz, Fabio C.; Babin, Klil R.; Leao, Rodrigo M.; Goldart, Evan M.; Bossert, Jennifer M.; Shaham, Yavin; Hope, Bruce T.] NIDA, Behav Neurosci Branch, IRP, NIH,Dept Hlth & Human Serv, Baltimore, MD 21224 USA. RP Hope, BT (reprint author), NIDA, Behav Neurosci Branch, IRP, NIH, 251 Bayview Dr, Baltimore, MD 21224 USA. EM bhope@intra.nida.nih.gov RI Hope, Bruce/A-9223-2010 OI Hope, Bruce/0000-0001-5804-7061 FU National Institute on Drug Abuse, Intramural Research Program, National Institutes of Health FX This work was supported by the National Institute on Drug Abuse, Intramural Research Program, National Institutes of Health. NR 53 TC 32 Z9 32 U1 1 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 MAY 28 PY 2014 VL 34 IS 22 BP 7437 EP 7446 DI 10.1523/JNEUROSCI.0238-14.2014 PG 10 WC Neurosciences SC Neurosciences & Neurology GA AI8CE UT WOS:000337131800005 PM 24872549 ER PT J AU Marchant, NJ Rabei, R Kaganovsky, K Caprioli, D Bossert, JM Bonci, A Shaham, Y AF Marchant, Nathan J. Rabei, Rana Kaganovsky, Konstantin Caprioli, Daniele Bossert, Jennifer M. Bonci, Antonello Shaham, Yavin TI A Critical Role of Lateral Hypothalamus in Context-Induced Relapse to Alcohol Seeking after Punishment-Imposed Abstinence SO JOURNAL OF NEUROSCIENCE LA English DT Article DE alcohol; context; lateral hypothalamus; nucleus accumbens; punishment; relapse ID NUCLEUS-ACCUMBENS SHELL; DOPAMINE D-1-FAMILY RECEPTORS; CUE-INDUCED REINSTATEMENT; MEDIAL PREFRONTAL CORTEX; VENTRAL TEGMENTAL AREA; COCAINE SEEKING; DRUG-SEEKING; REWARD-SEEKING; FEEDING-BEHAVIOR; HEROIN SEEKING AB In human alcoholics, abstinence is often self-imposed, despite alcohol availability, because of the negative consequences of excessive use. During abstinence, relapse is often triggered by exposure to contexts associated with alcohol use. We recently developed a rat model that captures some features of this human condition: exposure to the alcohol self-administration environment (context A), after punishment-imposed suppression of alcohol self-administration in a different environment (context B), provoked renewal of alcohol seeking in alcohol-preferring P rats. The mechanisms underlying context-induced renewal of alcohol seeking after punishment-imposed abstinence are unknown. Here, we studied the role of the lateral hypothalamus (LH) and its forebrain projections in this effect. We first determined the effect of context-induced renewal of alcohol seeking on Fos (a neuronal activity marker) expression in LH. We next determined the effect of LH reversible inactivation by GABA(A) + GABA(B) receptor agonists (muscimol + baclofen) on this effect. Finally, we determined neuronal activation in brain areas projecting to LH during context-induced renewal tests by measuring double labeling of the retrograde tracer cholera toxin subunit B (CTb; injected in LH) with Fos. Context-induced renewal of alcohol seeking after punishment-imposed abstinence was associated with increased Fos expression in LH. Additionally, renewal was blocked by muscimol + baclofen injections into LH. Finally, double-labeling analysis of CTb + Fos showed that context-induced renewal of alcohol seeking after punishment-imposed abstinence was associated with selective activation of accumbens shell neurons projecting to LH. The results demonstrate an important role of LH in renewal of alcohol seeking after punishment-imposed abstinence and suggest a role of accumbens shell projections to LH in this form of relapse. C1 [Marchant, Nathan J.; Rabei, Rana; Kaganovsky, Konstantin; Caprioli, Daniele; Bossert, Jennifer M.; Shaham, Yavin] NIDA, Behav Neurosci Res Branch, NIH, Dept Hlth & Human Serv, Baltimore, MD 21224 USA. [Bonci, Antonello] NIDA, Cellular Neurobiol Res Branch, Intramural Res Program, NIH,Dept Hlth & Human Serv, Baltimore, MD 21224 USA. [Marchant, Nathan J.] Univ Melbourne, Florey Inst Neurosci & Mental Hlth, Parkville, Vic 3052, Australia. [Bonci, Antonello] Johns Hopkins Univ, Solomon H Snyder Dept Neurosci, Baltimore, MD 21287 USA. [Bonci, Antonello] Johns Hopkins Univ, Dept Psychiat, Baltimore, MD 21287 USA. RP Marchant, NJ (reprint author), Biomed Res Ctr, Room 08A721,251 Bayview Blvd, Baltimore, MD 21224 USA. EM nathan.marchant@nih.gov OI Kaganovsky, Konstantin/0000-0002-1577-109X; Marchant, Nathan/0000-0001-8269-0532 FU National Institute on Drug Abuse, Intramural Research Program; National Health and Medical Research Council [1053308] FX This work was supported by the National Institute on Drug Abuse, Intramural Research Program. N.J.M. received support from Early Career Fellowship 1053308 by the National Health and Medical Research Council. NR 65 TC 15 Z9 15 U1 1 U2 6 PU SOC NEUROSCIENCE PI WASHINGTON PA 11 DUPONT CIRCLE, NW, STE 500, WASHINGTON, DC 20036 USA SN 0270-6474 J9 J NEUROSCI JI J. Neurosci. PD MAY 28 PY 2014 VL 34 IS 22 BP 7447 EP 7457 DI 10.1523/JNEUROSCI.0256-14.2014 PG 11 WC Neurosciences SC Neurosciences & Neurology GA AI8CE UT WOS:000337131800006 PM 24872550 ER PT J AU Chen, GY Qju, HL Prasad, PN Chen, XY AF Chen, Guanying Qju, Hailong Prasad, Paras N. Chen, Xiaoyuan TI Upconversion Nanoparticles: Design, Nanochemistry, and Applications in Theranostics SO CHEMICAL REVIEWS LA English DT Review ID NEAR-INFRARED LIGHT; RESONANCE ENERGY-TRANSFER; EARTH FLUORIDE NANOCRYSTALS; PHOTON-UPCONVERTING NANOPARTICLES; SURFACE-PLASMON RESONANCE; RAY COMPUTED-TOMOGRAPHY; LANTHANIDE-DOPED NANOCRYSTALS; CORE-SHELL NANOPARTICLES; DENSITY-FUNCTIONAL CALCULATIONS; CONVERTING PHOSPHOR TECHNOLOGY C1 [Chen, Guanying; Qju, Hailong] Harbin Inst Technol, Sch Chem Engn & Technol, Harbin 150001, Heilongjiang, Peoples R China. [Chen, Guanying; Qju, Hailong; Prasad, Paras N.] SUNY Buffalo, Dept Chem, Buffalo, NY 14260 USA. [Chen, Guanying; Qju, Hailong; Prasad, Paras N.] SUNY Buffalo, Inst Lasers Photon & Biophoton, Buffalo, NY 14260 USA. [Prasad, Paras N.] Korea Univ, Dept Chem, Seoul 136701, South Korea. [Chen, Xiaoyuan] Natl Inst Biomed Imaging & Bioengn, Lab Mol Imaging & Nanomed, NIH, Bethesda, MD 20892 USA. RP Chen, GY (reprint author), Harbin Inst Technol, Sch Chem Engn & Technol, Harbin 150001, Heilongjiang, Peoples R China. EM guanying@buffalo.edu; pnprasad@buffalo.edu; shawn.chen@nih.gov RI Chen, Guanying/D-8584-2011 OI Chen, Guanying/0000-0002-4789-1176 FU National Key Basic Research Program (973 Project) [2013CB733802, 2014CB744503]; Natural Science Foundation of China [51102066, 81371596]; Program for Basic Research Excellent Talents in Harbin Institute of Technology [BRETIII 2012018]; Intramural Research Program (IRP) of the National Institute of Biomedical Imaging and Bioengineering (NIBIB), National Institutes of Health (NIH) FX This work was supported by the National Key Basic Research Program (973 Project) (2013CB733802, 2014CB744503), the Natural Science Foundation of China (No. 51102066, 81371596), the Program for Basic Research Excellent Talents in Harbin Institute of Technology (BRETIII 2012018), and the Intramural Research Program (IRP) of the National Institute of Biomedical Imaging and Bioengineering (NIBIB), National Institutes of Health (NIH). NR 468 TC 467 Z9 475 U1 153 U2 923 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0009-2665 EI 1520-6890 J9 CHEM REV JI Chem. Rev. PD MAY 28 PY 2014 VL 114 IS 10 BP 5161 EP 5214 DI 10.1021/cr400425h PG 54 WC Chemistry, Multidisciplinary SC Chemistry GA AI1SV UT WOS:000336635900002 PM 24605868 ER PT J AU Costa, VD Averbeck, BB AF Costa, Vincent D. Averbeck, Bruno B. TI Looking into the future SO ELIFE LA English DT Editorial Material ID PARIETAL CORTEX; POSITION; NEURONS; SYSTEM C1 [Costa, Vincent D.; Averbeck, Bruno B.] NIMH, Neuropsychol Lab, Bethesda, MD 20892 USA. RP Costa, VD (reprint author), NIMH, Neuropsychol Lab, Bethesda, MD 20892 USA. EM vincent.costa@nih.gov RI Costa, Vincent/A-2086-2015 OI Costa, Vincent/0000-0002-5412-8945 NR 9 TC 2 Z9 2 U1 1 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 MAY 28 PY 2014 VL 3 AR e03146 DI 10.7554/eLife.03146 PG 3 WC Biology SC Life Sciences & Biomedicine - Other Topics GA AI2CV UT WOS:000336665600001 PM 24872505 ER PT J AU Cummings, SR Studenski, S Ferrucci, L AF Cummings, Steven R. Studenski, Stephanie Ferrucci, Luigi TI A Diagnosis of Dismobility-Giving Mobility Clinical Visibility A Mobility Working Group Recommendation SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Editorial Material ID SUBSEQUENT DISABILITY; PHYSICAL PERFORMANCE; OLDER-ADULTS; GAIT SPEED C1 [Cummings, Steven R.] Calif Pacific Med Ctr, Res Inst, San Francisco Coordinating Ctr, San Francisco, CA 94107 USA. [Studenski, Stephanie; Ferrucci, Luigi] NIA, Intramural Program, Baltimore, MD 21224 USA. RP Cummings, SR (reprint author), Calif Pacific Med Ctr, Res Inst, San Francisco Coordinating Ctr, 185 Berry St,Ste 5700, San Francisco, CA 94107 USA. EM scummings@sfcc-cpmc.net FU Intramural NIH HHS [Z01 AG000015-49] NR 10 TC 41 Z9 41 U1 2 U2 8 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 MAY 28 PY 2014 VL 311 IS 20 BP 2061 EP 2062 DI 10.1001/jama.2014.3033 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA AH8MQ UT WOS:000336392400016 PM 24763978 ER PT J AU Cotton, PB Durkalski, V Romagnuolo, J Pauls, Q Fogel, E Tarnasky, P Aliperti, G Freeman, M Kozarek, R Jamidar, P Wilcox, M Serrano, J Brawman-Mintzer, O Elta, G Mauldin, P Thornhill, A Hawes, R Wood-Williams, A Orrell, K Drossman, D Robuck, P AF Cotton, Peter B. Durkalski, Valerie Romagnuolo, Joseph Pauls, Qi Fogel, Evan Tarnasky, Paul Aliperti, Giuseppe Freeman, Martin Kozarek, Richard Jamidar, Priya Wilcox, Mel Serrano, Jose Brawman-Mintzer, Olga Elta, Grace Mauldin, Patrick Thornhill, Andre Hawes, Robert Wood-Williams, April Orrell, Kyle Drossman, Douglas Robuck, Patricia TI Effect of Endoscopic Sphincterotomy for Suspected Sphincter of Oddi Dysfunction on Pain-Related Disability Following Cholecystectomy The EPISOD Randomized Clinical Trial SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Article ID INTERNATIONAL NEUROPSYCHIATRIC INTERVIEW; FUNCTIONAL GASTROINTESTINAL DISORDERS; FINDINGS TYPE-I; HEALTH-STATUS; RISK-FACTORS; DSM-IV; ERCP; GALLBLADDER; SYMPTOMS; DISEASE AB IMPORTANCE Abdominal pain after cholecystectomy is common and may be attributed to sphincter of Oddi dysfunction. Management often involves endoscopic retrograde cholangiopancreatography (ERCP) with manometry and sphincterotomy. OBJECTIVE To determine whether endoscopic sphincterotomy reduces pain and whether sphincter manometric pressure is predictive of pain relief. DESIGN, SETTING, AND PATIENTS Multicenter, sham-controlled, randomized trial involving 214 patients with pain after cholecystectomy without significant abnormalities on imaging or laboratory studies, and no prior sphincter treatment or pancreatitis randomly assigned (August 6, 2008-March 23, 2012) to undergo sphincterotomy or sham therapy at 7 referral medical centers. One-year follow-up was blinded. The final follow-up visit was March 21, 2013. INTERVENTIONS After ERCP, patients were randomized 2: 1 to sphincterotomy (n = 141) or sham (n = 73) irrespective of manometry findings. Those randomized to sphincterotomy with elevated pancreatic sphincter pressures were randomized again (1: 1) to biliary or to both biliary and pancreatic sphincterotomies. Seventy-two were entered into an observational study with conventional ERCP managemeny. MAIN OUTCOMES AND MEASURES Success of treatment was defined as less than 6 days of disability due to pain in the prior 90 days both at months 9 and 12 after randomization, with no narcotic use and no further sphincter intervention. RESULTS Twenty-seven patients (37%; 95% CI, 25.9%-48.1%) in the sham treatment group vs 32 (23%; 95% CI, 15.8%-29.6%) in the sphincterotomy group experienced successful treatment (adjusted risk difference, -15.6%; 95% CI, -28.0% to -3.3%; P =.01). Of the patients with pancreatic sphincter hypertension, 14 (30%; 95% CI, 16.7%-42.9%) who underwent dual sphincterotomy and 10 (20%; 95% CI, 8.7%-30.5%) who underwent biliary sphincterotomy alone experienced successful treatment. Thirty-seven treated patients (26%; 95% CI, 19%-34%) and 25 patients (34%; 95% CI, 23%-45%) in the sham group underwent repeat ERCP interventions (P =.22). Manometry results were not associated with the outcome. No clinical subgroups appeared to benefit from sphincterotomy more than others. Pancreatitis occurred in 15 patients (11%) after primary sphincterotomies and in 11 patients (15%) in the sham group. Of the nonrandomized patients in the observational study group, 5 (24%; 95% CI, 6%-42%) who underwent biliary sphincterotomy, 12 (31%; 95% CI, 16%-45%) who underwent dual sphincterotomy, and 2 (17%; 95% CI, 0%-38%) who did not undergo sphincterotomy had successful treatment. CONCLUSIONS AND RELEVANCE In patients with abdominal pain after cholecystectomy undergoing ERCP with manometry, sphincterotomy vs sham did not reduce disability due to pain. These findings do not support ERCP and sphincterotomy for these patients. C1 [Cotton, Peter B.; Durkalski, Valerie; Romagnuolo, Joseph; Pauls, Qi; Mauldin, Patrick; Thornhill, Andre; Hawes, Robert; Wood-Williams, April; Orrell, Kyle] Med Univ S Carolina, Charleston, SC 29425 USA. [Fogel, Evan] Indiana Univ, Indianapolis, IN 46204 USA. [Tarnasky, Paul] Dallas Med Ctr, Dallas, TX USA. [Aliperti, Giuseppe] Midwest Therapeut Endoscopy Consultants, St Louis, MO USA. [Freeman, Martin] Univ Minnesota, Sch Med, Minneapolis, MN 55455 USA. [Kozarek, Richard] Virginia Mason Med Ctr, Seattle, WA 98101 USA. [Jamidar, Priya] Yale Univ, New Haven, CT USA. [Wilcox, Mel] Univ Alabama Birmingham, Birmingham, AL USA. [Serrano, Jose; Robuck, Patricia] Natl Inst Diabet & Digest & Kidney Dis, Bethesda, MD USA. [Brawman-Mintzer, Olga] Ralph H Johnson VA Med Ctr, Charleston, SC USA. [Elta, Grace] Univ Michigan, Ann Arbor, MI 48109 USA. [Hawes, Robert] Florida Hosp, Orlando, FL USA. [Drossman, Douglas] Univ N Carolina, Chapel Hill, NC USA. [Drossman, Douglas] Drossman Gastroenterol PLLC, Chapel Hill, NC USA. RP Cotton, PB (reprint author), Med Univ S Carolina, Ctr Digest Dis, ART 7094,MSC 290,25 Courtenay Dr, Charleston, SC 29425 USA. EM cottonp@musc.edu FU National Institutes of Diabetes and Digestive and Kidney Diseases [U01 DK074739] FX This study was funded by grant U01 DK074739 from the National Institutes of Diabetes and Digestive and Kidney Diseases. NR 40 TC 38 Z9 39 U1 12 U2 16 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 MAY 28 PY 2014 VL 311 IS 20 BP 2101 EP 2109 DI 10.1001/jama.2014.5220 PG 9 WC Medicine, General & Internal SC General & Internal Medicine GA AH8MQ UT WOS:000336392400026 PM 24867013 ER PT J AU Arany, PR Cho, A Hunt, TD Sidhu, G Shin, K Hahm, E Huang, GX Weaver, J Chen, ACH Padwa, BL Hamblin, MR Barcellos-Hoff, MH Kulkarni, AB Mooney, DJ AF Arany, Praveen R. Cho, Andrew Hunt, Tristan D. Sidhu, Gursimran Shin, Kyungsup Hahm, Eason Huang, George X. Weaver, James Chen, Aaron Chih-Hao Padwa, Bonnie L. Hamblin, Michael R. Barcellos-Hoff, Mary Helen Kulkarni, Ashok B. Mooney, David J. TI Photoactivation of Endogenous Latent Transforming Growth Factor-beta 1 Directs Dental Stem Cell Differentiation for Regeneration SO SCIENCE TRANSLATIONAL MEDICINE LA English DT Article ID GROWTH-FACTOR-BETA; LEVEL LASER IRRADIATION; IN-VITRO; PULP COMPLEX; BONE-MARROW; ACTIVATION; TGF-BETA-1; AMELOBLASTS; PROTEINS; MATRIX AB Rapid advancements in the field of stem cell biology have led to many current efforts to exploit stem cells as therapeutic agents in regenerative medicine. However, current ex vivo cell manipulations common to most regenerative approaches create a variety of technical and regulatory hurdles to their clinical translation, and even simpler approaches that use exogenous factors to differentiate tissue-resident stem cells carry significant off-target side effects. We show that non-ionizing, low-power laser (LPL) treatment can instead be used as a minimally invasive tool to activate an endogenous latent growth factor complex, transforming growth factor-beta 1 (TGF-beta 1), that subsequently differentiates host stem cells to promote tissue regeneration. LPL treatment induced reactive oxygen species (ROS) in a dose-dependent manner, which, in turn, activated latent TGF-beta 1 (LTGF-beta 1) via a specific methionine residue (at position 253 on LAP). Laser-activated TGF-beta 1 was capable of differentiating human dental stem cells in vitro. Further, an in vivo pulp capping model in rat teeth demonstrated significant increase in dentin regeneration after LPL treatment. These in vivo effects were abrogated in TGF-LPL-induced receptor II (TGF-beta RII) conditional knockout (DSPP(Cre)TGF-beta RIIfl/fl) mice or when wild-type mice were given a TGF-beta RI inhibitor. These findings indicate a pivotal role for TGF-beta in mediating LPL-induced dental tissue regeneration. More broadly, this work outlines a mechanistic basis for harnessing resident stem cells with a light-activated endogenous cue for clinical regenerative applications. C1 [Arany, Praveen R.; Hunt, Tristan D.; Sidhu, Gursimran; Shin, Kyungsup; Hahm, Eason; Huang, George X.; Mooney, David J.] Harvard Univ, Sch Engn & Appl Sci, Cambridge, MA 02138 USA. [Arany, Praveen R.; Weaver, James; Mooney, David J.] Wyss Inst Biol Inspired Engn, Boston, MA 02115 USA. [Arany, Praveen R.; Shin, Kyungsup] Harvard Univ, Sch Dent Med, Boston, MA 02115 USA. [Arany, Praveen R.] Leder Human Biol & Translat Med, Boston, MA 02115 USA. [Arany, Praveen R.; Cho, Andrew; Kulkarni, Ashok B.] Natl Inst Dent & Craniofacial Res, Bethesda, MD 20892 USA. [Chen, Aaron Chih-Hao; Hamblin, Michael R.] Massachusetts Gen Hosp, Wellman Ctr Photomed, Boston, MA 02114 USA. [Padwa, Bonnie L.] Childrens Hosp, Boston, MA 02115 USA. [Hamblin, Michael R.] Harvard Univ, Sch Med, Dept Dermatol, Boston, MA 02115 USA. [Hamblin, Michael R.] MIT, Harvard Mit Div Hlth Sci & Technol, Cambridge, MA 02139 USA. [Barcellos-Hoff, Mary Helen] NYU, Sch Med, New York, NY 10016 USA. RP Mooney, DJ (reprint author), Harvard Univ, Sch Engn & Appl Sci, Cambridge, MA 02138 USA. EM mooneyd@seas.harvard.edu OI Barcellos-Hoff, Mary Helen/0000-0002-5994-9558 FU Harvard Presidential Scholarship; Wyss institute, Harvard Catalyst; Harvard Clinical and Translational Science Center [National Center for Research Resources (NCRR)]; National Center for Advancing Translational Sciences (NCATS); NIH [1UL1 TR001102-01]; Harvard University; [R37-DE-013349]; [R01-DE019023-01]; [R01-AI-050875]; [ZIA-DE-000698] FX R37-DE-013349 (D.J.M.), R01-DE019023-01, R01-AI-050875 (M.R.H.), ZIA-DE-000698 (A.B.K.), Harvard Presidential Scholarship (P.R.A.), Wyss institute, Harvard Catalyst, Harvard Clinical and Translational Science Center [National Center for Research Resources (NCRR) and National Center for Advancing Translational Sciences (NCATS), NIH, 1UL1 TR001102-01, and financial contributions from Harvard University and its affiliated academic health care centers], and the intramural research program, NIDCR, NIH (A.B.K. and P.R.A.). The content is solely the responsibility of the authors and does not necessarily represent the official views of Harvard Catalyst, Harvard University and its affiliated academic health care centers, or the NIH. NR 45 TC 21 Z9 22 U1 0 U2 33 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 MAY 28 PY 2014 VL 6 IS 238 AR 238ra69 DI 10.1126/scitranslmed.3008234 PG 11 WC Cell Biology; Medicine, Research & Experimental SC Cell Biology; Research & Experimental Medicine GA AI2DZ UT WOS:000336668900002 PM 24871130 ER PT J AU Zabow, G Dodd, SJ Koretsky, AP AF Zabow, Gary Dodd, Stephen J. Koretsky, Alan P. TI Ellipsoidal Microcavities: Electromagnetic Properties, Fabrication, and Use as Multispectral MRI Agents SO SMALL LA English DT Article DE ellipsoidal colloids; magnetic microparticles; MRI contrast agents; nanofabrication ID PARTICLES; FIELD C1 [Zabow, Gary; Dodd, Stephen J.; Koretsky, Alan P.] NINDS, Lab Funct & Mol Imaging, NIH, Bethesda, MD 20892 USA. [Zabow, Gary] NIST, Electromagnet Div, Phys Measurement Lab, Boulder, CO 80305 USA. RP Zabow, G (reprint author), NINDS, Lab Funct & Mol Imaging, NIH, Bethesda, MD 20892 USA. EM zabowg@ninds.nih.gov RI Koretsky, Alan/C-7940-2015 OI Koretsky, Alan/0000-0002-8085-4756 FU NIH NINDS Intramural Research Program FX This work was supported in part by the NIH NINDS Intramural Research Program. We thank the NIH Mouse Imaging Facility for use of the 14T MRI, and Dr. John Moreland for useful discussion and for NIST cleanroom access. NR 23 TC 4 Z9 4 U1 1 U2 20 PU WILEY-V C H VERLAG GMBH PI WEINHEIM PA BOSCHSTRASSE 12, D-69469 WEINHEIM, GERMANY SN 1613-6810 EI 1613-6829 J9 SMALL JI Small PD MAY 28 PY 2014 VL 10 IS 10 BP 1902 EP 1907 DI 10.1002/smll.201303045 PG 6 WC Chemistry, Multidisciplinary; Chemistry, Physical; Nanoscience & Nanotechnology; Materials Science, Multidisciplinary; Physics, Applied; Physics, Condensed Matter SC Chemistry; Science & Technology - Other Topics; Materials Science; Physics GA AI1KX UT WOS:000336611000003 PM 24623519 ER PT J AU Anderson, LA Atman, AA McShane, CM Titmarsh, GJ Engels, EA Koshiol, J AF Anderson, L. A. Atman, A. A. McShane, C. M. Titmarsh, G. J. Engels, E. A. Koshiol, J. TI Common infection-related conditions and risk of lymphoid malignancies in older individuals SO BRITISH JOURNAL OF CANCER LA English DT Article ID NON-HODGKIN-LYMPHOMA; CHRONIC LYMPHOCYTIC-LEUKEMIA; MULTIPLE-MYELOMA; MEDICAL HISTORY; CELL LYMPHOMA; INFLAMMATORY CONDITIONS; IMMUNE; POLYMORPHISMS; CELLULITIS; HEPATITIS AB Background: Chronic antigenic stimulation may initiate non-Hodgkin (NHL) and Hodgkin lymphoma (HL) development. Antecedent, infection-related conditions have been associated, but evidence by lymphoproliferative subtype is limited. Methods: From the US SEER-Medicare database, 44 191 NHL, 1832 HL and 200 000 population-based controls, frequency matched to all SEER cancer cases, were selected. Logistic regression models, adjusted for potential confounders, compared infection-related conditions in controls with HL and NHL patients and by the NHL subtypes diffuse large B-cell, T-cell, follicular and marginal zone lymphoma (MZL). Stratification by race was undertaken. Results: Respiratory tract infections were broadly associated with NHL, particularly MZL. Skin infections were associated with a 15-28% increased risk of NHL and with most NHL subtypes, particularly cellulitis with T-cell lymphoma (OR 1.36, 95% CI 1.24-1.49). Only herpes zoster remained associated with HL following Bonferroni correction (OR 1.55, 95% CI 1.28-1.87). Gastrointestinal and urinary tract infections were not strongly associated with NHL or HL. In stratified analyses by race, sinusitis, pharyngitis, bronchitis and cellulitis showed stronger associations with total NHL in blacks than whites (P < 0.001). Conclusions: Infections may contribute to the aetiologic pathway and/or be markers of underlying immune modulation. Precise elucidation of these mechanisms may provide important clues for understanding how immune disturbance contributes to lymphoma. C1 [Anderson, L. A.; Atman, A. A.; McShane, C. M.; Titmarsh, G. J.] Queens Univ Belfast, Ctr Publ Hlth, Belfast BT12 6BJ, Antrim, North Ireland. [Engels, E. A.; Koshiol, J.] NCI, Div Canc Epidemiol & Genet, NIH, Bethesda, MD 20892 USA. RP Anderson, LA (reprint author), Queens Univ Belfast, Ctr Publ Hlth, Belfast BT12 6BJ, Antrim, North Ireland. EM l.anderson@qub.ac.uk OI Anderson, Lesley/0000-0002-1000-3649 FU Intramural Research Program of the National Cancer Institute; Queen's University Belfast FX This work was supported by the Intramural Research Program of the National Cancer Institute. GT is a PhD student at the Queen's University Belfast in receipt of funding from MPD Voice. CMS is a PhD student at the Queen's University Belfast in receipt of a Department for Employment and Learning (Northern Ireland) funded scholarship. This study used the linked SEER-Medicare database. The interpretation and reporting of these data are the sole responsibility of the authors. We acknowledge the efforts of the Applied Research Program, NCI; the Office of Research, Development and Information, Centers for Medicare and Medicaid Services; Information Management Services, Inc.; and the Surveillance, Epidemiology, and End Results (SEER) Program tumour registries in the creation of the SEER-Medicare database. We also thank Dr Winnie Ricker, Information Management Services, Rockville, MD, USA for constructing and analysing the data set. NR 34 TC 5 Z9 5 U1 0 U2 2 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 MAY 27 PY 2014 VL 110 IS 11 BP 2796 EP 2803 DI 10.1038/bjc.2014.173 PG 8 WC Oncology SC Oncology GA AI8HB UT WOS:000337150600019 PM 24691420 ER PT J AU Winkler, CW Taylor, KG Peterson, KE AF Winkler, Clayton W. Taylor, Katherine G. Peterson, Karin E. TI Location Is Everything: let-7b microRNA and TLR7 Signaling Results in a Painful TRP SO SCIENCE SIGNALING LA English DT Article ID CAUSES NEURODEGENERATION; NEGATIVE REGULATOR; RECEPTOR 7; AGONISTS; PROTEIN AB Extracellular let-7b, a microRNA found in the central nervous system, affects neurons through its interaction with Toll-like receptor 7 (TLR7), but with divergent outcomes in different neurons. Lehmann et al. found that let-7b stimulation of cortical and hippocampal neurons led to neuronal apoptosis, whereas Park et al. report that let-7b activation of TLR7 stimulated the cation channel transient receptor potential A1 (TRPA1) on dorsal root ganglia sensory neurons and induced pain responses. The primary difference that may influence these distinct responses to let-7b is the localization of TLR7 to the endosome in the cortical and hippocampal neurons or the plasma membrane in the sensory neurons. These studies suggest that different types of neurons traffic TLR7 to distinct membrane locations, affecting the functional response of neurons to let-7b stimulation. C1 [Winkler, Clayton W.; Taylor, Katherine G.; Peterson, Karin E.] NIAID, Persistent Viral Dis Lab, Rocky Mt Labs, NIH, Hamilton, MT 59840 USA. RP Peterson, KE (reprint author), NIAID, Persistent Viral Dis Lab, Rocky Mt Labs, NIH, Hamilton, MT 59840 USA. EM petersonka@niaid.nih.gov RI Peterson, Karin/D-1492-2016 OI Peterson, Karin/0000-0003-4177-7249 NR 12 TC 6 Z9 6 U1 0 U2 14 PU AMER ASSOC ADVANCEMENT SCIENCE PI WASHINGTON PA 1200 NEW YORK AVE, NW, WASHINGTON, DC 20005 USA SN 1945-0877 EI 1937-9145 J9 SCI SIGNAL JI Sci. Signal. PD MAY 27 PY 2014 VL 7 IS 327 AR pe14 DI 10.1126/scisignal.2005407 PG 2 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA AI8OI UT WOS:000337178300002 PM 24866018 ER PT J AU de Messieres, M Huang, RK He, Y Lee, JC AF de Messieres, Michel Huang, Rick K. He, Yi Lee, Jennifer C. TI Amyloid Triangles, Squares, and Loops of Apolipoprotein C-III SO BIOCHEMISTRY LA English DT Article ID FIBRIL-FORMATION; A-I; CARDIOVASCULAR-SYSTEM; ALPHA-SYNUCLEIN; ATHEROSCLEROSIS; LIPOPROTEIN; INSIGHTS; MUTATION; DOMAIN; APOC3 AB While a significant component of atherosclerotic plaques has been characterized as amyloid, the specific proteins remain to be fully identified. Probable amyloidogenic proteins are apolipoproteins (Apos), which are vital for the formation and function of lipoproteins. ApoCIII is an abundant protein implicated in atherosclerosis, and we show it forms a ribbonlike looped amyloid, strikingly similar to that previously reported for ApoAI and ApoCII. Triangles and squares with a width of similar to 50 nm were also observed, which may be a novel form of amyloid or related to previously reported amyloid rings. C1 [de Messieres, Michel; Lee, Jennifer C.] NHLBI, Lab Mol Biophys, Bethesda, MD 20892 USA. [He, Yi] NHLBI, Prot Express Facil, Biochem & Biophys Ctr, Bethesda, MD 20892 USA. [Huang, Rick K.] NIAMSD, Struct Biol Res Lab, NIH, Bethesda, MD 20892 USA. RP Lee, JC (reprint author), NHLBI, Lab Mol Biophys, Bldg 10, Bethesda, MD 20892 USA. EM leej4@mail.nih.gov RI Lee, Jennifer/E-9658-2015 OI Lee, Jennifer/0000-0003-0506-8349 FU National Institutes of Health, National Heart, Lung and Blood Institute; National Institute of Arthritis and Musculoskeletal and Skin Diseases FX Supported by the Intramural Research Program at the National Institutes of Health, the National Heart, Lung and Blood Institute, and the National Institute of Arthritis and Musculoskeletal and Skin Diseases. NR 28 TC 8 Z9 8 U1 4 U2 7 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0006-2960 J9 BIOCHEMISTRY-US JI Biochemistry PD MAY 27 PY 2014 VL 53 IS 20 BP 3261 EP 3263 DI 10.1021/bi500502d PG 3 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA AI1SY UT WOS:000336636300001 PM 24804986 ER PT J AU Miranda, KM Wink, DA AF Miranda, Katrina M. Wink, David A. TI Persulfides and the cellular thiol landscape SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Editorial Material ID HYDROGEN-SULFIDE; METABOLISM; BIOLOGY; SULFUR C1 [Miranda, Katrina M.] Univ Arizona, Dept Chem & Biochem, Tucson, AZ 85721 USA. [Wink, David A.] NCI, Radiat Biol Branch, NIH, Bethesda, MD 20892 USA. RP Wink, DA (reprint author), NCI, Radiat Biol Branch, NIH, Bethesda, MD 20892 USA. EM wink@mail.nih.gov NR 15 TC 7 Z9 7 U1 0 U2 14 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD MAY 27 PY 2014 VL 111 IS 21 BP 7505 EP 7506 DI 10.1073/pnas.1405665111 PG 2 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA AH8TO UT WOS:000336411300015 PM 24828533 ER PT J AU Imashimizu, M Kashlev, M AF Imashimizu, Masahiko Kashlev, Mikhail TI Unveiling translocation intermediates of RNA polymerase SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Editorial Material ID 3.3 ANGSTROM RESOLUTION; STRUCTURAL BASIS; TRANSCRIPTION ELONGATION; TRIGGER LOOP; POL II; DYNAMICS; SITE; DROSOPHILA; MECHANISM; COMPLEX C1 [Imashimizu, Masahiko; Kashlev, Mikhail] NCI, Gene Regulat & Chromosome Biol Lab, Ctr Canc Res, Frederick, MD 21702 USA. RP Kashlev, M (reprint author), NCI, Gene Regulat & Chromosome Biol Lab, Ctr Canc Res, Frederick, MD 21702 USA. EM kashlevm@mail.nih.gov NR 27 TC 3 Z9 3 U1 1 U2 7 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD MAY 27 PY 2014 VL 111 IS 21 BP 7507 EP 7508 DI 10.1073/pnas.1406413111 PG 2 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA AH8TO UT WOS:000336411300016 PM 24828529 ER PT J AU Luque, D Gomez-Blanco, J Garriga, D Brilot, AF Gonzalez, JM Havens, WM Carrascosa, JL Trus, BL Verdaguer, N Ghabrial, SA Caston, JR AF Luque, Daniel Gomez-Blanco, Josue Garriga, Damia Brilot, Axel F. Gonzalez, Jose M. Havens, Wendy M. Carrascosa, Jose L. Trus, Benes L. Verdaguer, Nuria Ghabrial, Said A. Caston, Jose R. TI Cryo-EM near-atomic structure of a dsRNA fungal virus shows ancient structural motifs preserved in the dsRNA viral lineage SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE 3D cryo-EM; chrysovirus; structural homology; virus evolution ID PENICILLIUM-CHRYSOGENUM-VIRUS; MULTIPLE SEQUENCE ALIGNMENT; ELECTRON-MICROSCOPY; CAPSID PROTEIN; CARBOXYSOME SHELL; RNA VIRUS; EVOLUTION; IMAGE; CRYOMICROSCOPY; VISUALIZATION AB Viruses evolve so rapidly that sequence-based comparison is not suitable for detecting relatedness among distant viruses. Structure-based comparisons suggest that evolution led to a small number of viral classes or lineages that can be grouped by capsid protein (CP) folds. Here, we report that the CP structure of the fungal dsRNA Penicillium chrysogenum virus (PcV) shows the progenitor fold of the dsRNA virus lineage and suggests a relationship between lineages. Cryo-EM structure at near-atomic resolution showed that the 982-aa PcV CP is formed by a repeated alpha-helical core, indicative of gene duplication despite lack of sequence similarity between the two halves. Superimposition of secondary structure elements identified a single "hotspot" at which variation is introduced by insertion of peptide segments. Structural comparison of PcV and other distantly related dsRNA viruses detected preferential insertion sites at which the complexity of the conserved alpha-helical core, made up of ancestral structural motifs that have acted as a skeleton, might have increased, leading to evolution of the highly varied current structures. Analyses of structural motifs only apparent after systematic structural comparisons indicated that the hallmark fold preserved in the dsRNA virus lineage shares a long (spinal) alpha-helix tangential to the capsid surface with the head-tailed phage and herpesvirus viral lineage. C1 [Luque, Daniel; Gomez-Blanco, Josue; Gonzalez, Jose M.; Carrascosa, Jose L.; Caston, Jose R.] CSIC, Ctr Nacl Biotecnol, Dept Struct Macromol, Madrid 28049, Spain. [Luque, Daniel] Inst Salud Carlos III, Ctr Nacl Microbiol, Madrid 28220, Spain. [Garriga, Damia; Verdaguer, Nuria] CSIC, Inst Biol Mol Barcelona, E-08028 Barcelona, Spain. [Brilot, Axel F.] Brandeis Univ, Dept Biochem, Waltham, MA 02454 USA. [Havens, Wendy M.; Ghabrial, Said A.] Univ Kentucky, Dept Plant Pathol, Lexington, KY 40546 USA. [Trus, Benes L.] NIH, Imaging Sci Lab, Ctr Informat Technol, Bethesda, MD 20892 USA. RP Caston, JR (reprint author), CSIC, Ctr Nacl Biotecnol, Dept Struct Macromol, Campus Cantoblanco, Madrid 28049, Spain. EM jrcaston@cnb.csic.es RI Caston, Jose/L-5896-2014; Luque, Daniel/I-6467-2015; OI Caston, Jose/0000-0003-2350-9048; Luque, Daniel/0000-0002-0151-6020; Gonzalez, Jose M/0000-0001-5569-0705; Garriga, Damia/0000-0003-0410-538X; Brilot, Axel/0000-0001-8548-4224 FU Canadian National Science and Engineering Research Council; National Institutes of Health [P01 GM62580]; Spanish Ministry of Economy and Competitivity [BFU 2011-29038, BIO2011-24333, BIO BFU2011-25902]; National Institutes of Health Intramural Research Program; Center for Information Technology FX We thank N. Grigorieff for continuous technical and intellectual support, stimulating discussions, and critical reading of the manuscript; C. Xu for maintaining the Brandeis EM facility and help with data collection; and C. Mark for editorial assistance. A. F. B. was supported by a grant from the Canadian National Science and Engineering Research Council. The Brandeis EM facility is supported by National Institutes of Health Grant P01 GM62580. This work was supported by Spanish Ministry of Economy and Competitivity Grant BFU 2011-29038 (to J.L.C.), Grant BIO2011-24333 (to N. V.), and Grant BIO BFU2011-25902 (to J.R.C.), and by a grant from the National Institutes of Health Intramural Research Program and the Center for Information Technology (to B.L.T.). NR 47 TC 7 Z9 7 U1 0 U2 16 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 MAY 27 PY 2014 VL 111 IS 21 BP 7641 EP 7646 DI 10.1073/pnas.1404330111 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA AH8TO UT WOS:000336411300040 PM 24821769 ER PT J AU Onozawa, M Zhang, ZH Kim, YJ Goldberg, L Varga, T Bergsagel, PL Kuehl, WM Aplan, PD AF Onozawa, Masahiro Zhang, Zhenhua Kim, Yoo Jung Goldberg, Liat Varga, Tamas Bergsagel, P. Leif Kuehl, W. Michael Aplan, Peter D. TI Repair of DNA double-strand breaks by templated nucleotide sequence insertions derived from distant regions of the genome SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE polymorphism; TSIP; LINE-1; DNA patch ID INDEPENDENT LINE-1 RETROTRANSPOSITION; REVERSE-TRANSCRIPTASE INHIBITORS; CHROMOSOMAL TRANSLOCATIONS; SWITCH RECOMBINATION; STRUCTURAL VARIATION; REARRANGEMENTS; EVOLUTION; MUTATIONS; REVEALS; CAPTURE AB We used the I-SceI endonuclease to produce DNA double-strand breaks (DSBs) and observed that a fraction of these DSBs were repaired by insertion of sequences, which we termed "templated sequence insertions" (TSIs), derived from distant regions of the genome. These TSIs were derived from genic, retrotransposon, or telomere sequences and were not deleted from the donor site in the genome, leading to the hypothesis that they were derived from reverse-transcribed RNA. Cotransfection of RNA and an I-SceI expression vector demonstrated insertion of RNA-derived sequences at the DNA-DSB site, and TSIs were suppressed by reverse-transcriptase inhibitors. Both observations support the hypothesis that TSIs were derived from RNA templates. In addition, similar insertions were detected at sites of DNA DSBs induced by transcription activator-like effector nuclease proteins. Whole-genome sequencing of myeloma cell lines revealed additional TSIs, demonstrating that repair of DNA DSBs via insertion was not restricted to experimentally produced DNA DSBs. Analysis of publicly available databases revealed that many of these TSIs are polymorphic in the human genome. Taken together, these results indicate that insertional events should be considered as alternatives to gross chromosomal rearrangements in the interpretation of whole-genome sequence data and that this mutagenic form of DNA repair may play a role in genetic disease, exon shuffling, and mammalian evolution. C1 [Onozawa, Masahiro; Zhang, Zhenhua; Kim, Yoo Jung; Goldberg, Liat; Varga, Tamas; Kuehl, W. Michael; Aplan, Peter D.] NCI, Genet Branch, NIH, Bethesda, MD 20892 USA. [Bergsagel, P. Leif] Mayo Clin, Ctr Comprehens Canc, Scottsdale, AZ 85259 USA. RP Aplan, PD (reprint author), NCI, Genet Branch, NIH, Bethesda, MD 20892 USA. EM aplanp@mail.nih.gov RI Aplan, Peter/K-9064-2016 FU National Cancer Institute, NIH; Japan Society for the Promotion of Science FX We thank Drs. Paul Meltzer and Ilan Kirsch, and members of the P.D.A. laboratory for helpful discussions; Haruto Onozawa for technical assistance; and the National Institutes of Health (NIH) Mini-sequencing core for Sanger sequencing. This work was supported by the intramural program of the National Cancer Institute, NIH. M.O. was supported by the Japan Society for the Promotion of Science Postdoctoral Fellowships for Research Abroad program. NR 47 TC 21 Z9 21 U1 1 U2 18 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD MAY 27 PY 2014 VL 111 IS 21 BP 7729 EP 7734 DI 10.1073/pnas.1321889111 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA AH8TO UT WOS:000336411300055 PM 24821809 ER PT J AU Halemano, K Guo, KJ Heilman, KJ Barrett, BS Smith, DS Hasenkrug, KJ Santiago, ML AF Halemano, Kalani Guo, Kejun Heilman, Karl J. Barrett, Bradley S. Smith, Diana S. Hasenkrug, Kim J. Santiago, Mario L. TI Immunoglobulin somatic hypermutation by APOBEC3/Rfv3 during retroviral infection SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE humoral immunity; restriction factor; antibody repertoire profiling; affinity maturation; Friend retrovirus ID IN-VIVO; AFFINITY MATURATION; HIV-1 INFECTION; VIRUS-INFECTION; GENE; DEAMINATION; LEUKEMIA; DNA; RECEPTOR; MICE AB Somatic hypermutation (SHM) is an integral process in the development of high-affinity antibodies that are important for recovery from viral infections and vaccine-induced protection. Ig SHM occurs predominantly in germinal centers (GC) via the enzymatic activity of activation-induced deaminase (AID). In contrast, the evolutionarily related apolipoprotein B mRNA-editing enzyme, catalytic polypeptide 3 (APOBEC3) proteins are known to restrict retroviruses, including HIV-1. We previously reported that mouse APOBEC3 encodes Recovery from Friend virus 3 (Rfv3), a classical resistance gene in mice that promotes the neutralizing antibody response against retrovirus infection. We now show that APOBEC3/Rfv3 complements AID in driving Ig SHM during retrovirus infection. Analysis of antibody sequences from retrovirus-specific hybridomas and GC B cells from infected mice revealed Ig heavy-chain V genes with significantly increased C-to-T and G-to-A transitions in wild-type as compared with APOBEC3-defective mice. The context of the mutations was consistent with APOBEC3 but not AID mutational activity. These findings help explain the role of APOBEC3/Rfv3 in promoting the neutralizing antibody responses essential for recovery from retroviral infection and highlight APOBEC3-mediated deamination as a previously unidentified mechanism for antibody diversification in vivo. C1 [Halemano, Kalani; Guo, Kejun; Heilman, Karl J.; Barrett, Bradley S.; Smith, Diana S.; Santiago, Mario L.] Univ Colorado Denver, Dept Med, Aurora, CO 80045 USA. [Halemano, Kalani; Santiago, Mario L.] Univ Colorado Denver, Dept Microbiol & Immunol, Aurora, CO 80045 USA. [Hasenkrug, Kim J.] NIAID, Persistent Viral Dis Lab, Rocky Mt Labs, NIH, Hamilton, MT 59840 USA. RP Santiago, ML (reprint author), Univ Colorado Denver, Dept Med, Aurora, CO 80045 USA. EM mario.santiago@ucdenver.edu FU National Institutes of Health (NIH) [R01 AI090795]; University of Colorado Department of Medicine Early Career Scholar Program; NIH Division of Intramural Research; American Society for Microbiology FX We thank W. Greene, L. Wysocki, R. Pelanda, R. Torres, L. Pujunauski, J. Hagman, C. Dege, L. van Dyk, E. Janoff, D. Frank, and B. Palmer for reagents, technical advice and/or assistance. This work was supported by National Institutes of Health (NIH) Grant R01 AI090795 (to M. L. S.), the University of Colorado Department of Medicine Early Career Scholar Program (to M. L. S.), and by the NIH Division of Intramural Research (to K. J. Hasenkrug). K.H. was the recipient of a Robert D. Watkins Predoctoral Fellowship from the American Society for Microbiology. NR 40 TC 17 Z9 17 U1 2 U2 4 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD MAY 27 PY 2014 VL 111 IS 21 BP 7759 EP 7764 DI 10.1073/pnas.1403361111 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA AH8TO UT WOS:000336411300060 PM 24821801 ER PT J AU Anizan, S Ellefsen, K Concheiro, M Suzuki, M Rice, KC Baumann, MH Huestis, MA AF Anizan, Sebastien Ellefsen, Kayla Concheiro, Marta Suzuki, Masaki Rice, Kenner C. Baumann, Michael H. Huestis, Marilyn A. TI 3,4-Methylenedioxypyrovalerone (MDPV) and metabolites quantification in human and rat plasma by liquid chromatography-high resolution mass spectrometry SO ANALYTICA CHIMICA ACTA LA English DT Article DE MDPV; Synthetic cathinones; LC-MS/MS; HRMS; Metabolites ID BATH SALTS; SYNTHETIC CATHINONES; DESIGNER DRUG; IN-VITRO; 3,4-DIHYDROXYMETHAMPHETAMINE; AMPHETAMINE; MEPHEDRONE; TOXICOLOGY AB Synthetic cathinones are recreational drugs that mimic the effects of illicit stimulants like cocaine, amphetamine or Ecstasy. Among the available synthetic cathinones in the United States, 3,4-methylenedioxypyrovalerone (MDPV) is commonly abused and associated with dangerous side effects. MDPV is a dopamine transporter blocker 10-fold more potent than cocaine as a locomotor stimulant in rats. Previous in vitro and in vivo studies examining MDPV metabolism reported 3,4-dihydroxypyrovalerone (3,4-catechol-PV) and 4-hydroxy-3-methoxypyrovalerone (4-OH-3-MeO-PV) as the two primary metabolites. We developed and validated a liquid chromatography-high resolution mass spectrometry method to quantify MDPV and its primary metabolites in 100 mu L human and rat plasma. Plasma hydrolysis was followed by protein precipitation before analysis. Limits of detection were 0.1 mu g L (1), with linear ranges from 0.25 to 1000 mu g L (1). Process efficiency, matrix effect, total imprecision (%CV) and accuracy (%target) were 36-93%, from -8 to 12%, 2.1 to 7.3% and 86 to 109%, respectively. MDPV and metabolites were stable at room temperature for 24 h, 4 degrees C for 72 h and after 3 freeze-thaw cycles with less than 10% variability. Human-rat plasma cross validation demonstrated that rat plasma could be accurately quantified against a human plasma calibration curve. As proof of this method, rat plasma specimens were analyzed after intraperitoneal and subcutaneous dosing with MDPV (0.5 mg kg (1)). MDPV, 3,4-catechol-PV and 4-OH-3-MeO-PV concentrations ranged from not detected to 107.5 mu g L (1) prior to and up to 8 h after dosing. This method provides a simultaneous quantification of MDPV and two metabolites in plasma with good selectivity and sensitivity. Published by Elsevier B.V. C1 [Anizan, Sebastien; Ellefsen, Kayla; Concheiro, Marta; Huestis, Marilyn A.] NIDA, Intramural Res Program, NIH, Baltimore, MD 21224 USA. [Ellefsen, Kayla] Univ Maryland, Toxicol Program, Baltimore, MD 21201 USA. [Suzuki, Masaki; Rice, Kenner C.] NIDA, Drug Design & Synth Sect, Intramural Res Program, NIH, Baltimore, MD 21224 USA. [Suzuki, Masaki; Rice, Kenner C.] NIAAA, NIH, Baltimore, MD USA. [Baumann, Michael H.] NIDA, Designer Drug Res Unit, Intramural Res Program, NIH, Baltimore, MD 21224 USA. RP Huestis, MA (reprint author), NIDA, Chem & Drug Metab Biomed Res Ctr BRC, NIH, 251 Bayview Blvd,Suite 200 Room 05A721, Baltimore, MD 21224 USA. EM mhuestis@intra.nida.nih.gov FU Intramural Research Program of the National Institute on Drug Abuse (NIDA); National Institute on Alcohol Abuse and Alcoholism (NIAAA); National Institutes of Health (NIH) FX This research was supported by the Intramural Research Program of the National Institute on Drug Abuse (NIDA), and the National Institute on Alcohol Abuse and Alcoholism (NIAAA), National Institutes of Health (NIH). NR 29 TC 14 Z9 14 U1 2 U2 34 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0003-2670 EI 1873-4324 J9 ANAL CHIM ACTA JI Anal. Chim. Acta PD MAY 27 PY 2014 VL 827 BP 54 EP 63 DI 10.1016/j.aca.2014.04.015 PG 10 WC Chemistry, Analytical SC Chemistry GA AH2BN UT WOS:000335925800008 PM 24832995 ER PT J AU Sidharthan, S Kim, CW Murphy, AA Zhang, XZ Yang, J Lempicki, RA Sneller, MC Kottilil, S AF Sidharthan, Sreetha Kim, Cheol-Woo Murphy, Alison A. Zhang, Xiaozhen Yang, Jun Lempicki, Richard A. Sneller, Michael C. Kottilil, Shyam TI Hepatitis C-associated mixed cryoglobulinemic vasculitis induces differential gene expression in peripheral mononuclear cells SO FRONTIERS IN IMMUNOLOGY LA English DT Article DE hepatitis C; mixed cryoglobulinemia; vasculitis; interferon-stimulated genes ID HUMAN-IMMUNODEFICIENCY-VIRUS; EXTRAHEPATIC MANIFESTATIONS; HCV INFECTION; RECRUITMENT; THERAPY; LIVER; PATHOGENESIS; REPLICATION; COINFECTION; CHEMOKINES AB This study examines the distinct gene expression profile of peripheral blood mononuclear cells from patients with chronic hepatitis C infection and mixed cryoglobulinemic (MC) vasculitis. Our DNA microarray analysis indicates that hepatitis C virus (HCV)-associated MC vasculitis is characterized by compromised neutrophil function, impaired chemotaxis, and increased interferon-stimulated gene (ISG) expression, contributing to overall MC pathogenesis and end-organ damage. Increased ISG expression is suggestive of an enhanced endogenous interferon gene signature. PBMC depletion assays demonstrate that this increased expression is likely due to an activation of monocytes and not a direct result of B cell expansion. Notably, this monocyte activation of ISG expression in HCV-associated MC vasculitis suggests a poor predictor status of interferon-based treatment. Further analysis of PBMC gene expression profiles before and after in vivo B cell depletion therapy is critical to completely understanding the mechanisms of MC vasculitis pathogenesis. C1 [Sidharthan, Sreetha] NIH, Dept Crit Care Med, Ctr Clin, US Dept HHS, Bethesda, MD 20892 USA. [Kim, Cheol-Woo] Inha Univ, Dept Internal Med, Inchon, South Korea. [Murphy, Alison A.; Zhang, Xiaozhen; Sneller, Michael C.; Kottilil, Shyam] NIAID, Immunoregulat Lab, NIH, US Dept HHS, Bethesda, MD 20892 USA. [Yang, Jun; Lempicki, Richard A.] Leidos Biomed Res Inc, Frederick Natl Lab Canc Res, Clin Res Directorate, Clin Monitoring Res Program, Frederick, MD USA. RP Kottilil, S (reprint author), NIAID, Immunopathogenesis Sect, Immunoregulat Lab, NIH, Bldg 10,Room 11N204, Bethesda, MD 20892 USA. EM skottili@niaid.nih.gov FU intramural program of the National Institute of Allergy and Infectious Diseases at the National Institutes of Health, Bethesda, MD, USA FX This study has been funded in whole with the federal funds from the intramural program of the National Institute of Allergy and Infectious Diseases at the National Institutes of Health, Bethesda, MD, USA. Disclaimer: the views or policies of the Department of Health and Human Services are not necessarily reflected in this content. The U.S. Government does not endorse any trade names, commercial products, or organizations mentioned. NR 30 TC 2 Z9 3 U1 0 U2 1 PU FRONTIERS RESEARCH FOUNDATION PI LAUSANNE PA PO BOX 110, LAUSANNE, 1015, SWITZERLAND SN 1664-3224 J9 FRONT IMMUNOL JI Front. Immunol. PD MAY 27 PY 2014 VL 5 BP 1 EP 13 AR 248 DI 10.3389/fimmu.2014.00248 PG 13 WC Immunology SC Immunology GA CH7OD UT WOS:000354225600001 PM 24904592 ER PT J AU Romero, R Hassan, SS Gajer, P Tarca, AL Fadrosh, DW Bieda, J Chaemsaithong, P Miranda, J Chaiworapongsa, T Ravel, J AF Romero, Roberto Hassan, Sonia S. Gajer, Pawel Tarca, Adi L. Fadrosh, Douglas W. Bieda, Janine Chaemsaithong, Piya Miranda, Jezid Chaiworapongsa, Tinnakorn Ravel, Jacques TI The vaginal microbiota of pregnant women who subsequently have spontaneous preterm labor and delivery and those with a normal delivery at term SO MICROBIOME LA English DT Article DE Infection-induced preterm delivery; Histologic chorioamnionitis; Prematurity; Vaginal flora; Vaginal microbiome ID AMNIOTIC-FLUID INFECTION; LOW-BIRTH-WEIGHT; ASYMPTOMATIC BACTERIAL VAGINOSIS; POLYMERASE-CHAIN-REACTION; RIBOSOMAL-RNA GENES; INTRAAMNIOTIC INFECTION; UREAPLASMA-UREALYTICUM; INTACT MEMBRANES; PREMATURE LABOR; RISK-FACTOR AB Background: This study was undertaken to determine whether the vaginal microbiota of pregnant women who subsequently had a spontaneous preterm delivery is different from that of women who had a term delivery. Results: This was a nested case-control study of pregnant women who had a term delivery (controls) and those who had a spontaneous preterm delivery before 34 weeks of gestation (cases). Samples of vaginal fluid were collected longitudinally and stored at -70 degrees C until assayed. A microbial survey using pyrosequencing of V1-V3 regions of 16S rRNA genes was performed. We tested the hypothesis of whether the relative abundance of individual microbial species (phylotypes) was different between women who had a term versus preterm delivery. A suite of bioinformatic and statistical tools, including linear mixed effects models and generalized estimating equations, was used. We show that: 1) the composition of the vaginal microbiota during normal pregnancy changed as a function of gestational age, with an increase in the relative abundance of four Lactobacillus spp., and decreased in anaerobe or strict-anaerobe microbial species as pregnancy progressed; 2) no bacterial taxa differed in relative abundance between women who had a spontaneous preterm delivery and those who delivered at term; and 3) no differences in the frequency of the vaginal community state types (CST I, III, IV-B) between women who delivered at term and those who delivered preterm were detected. Conclusions: The bacterial taxa composition and abundance of vaginal microbial communities, characterized with 16S rRNA gene sequence-based techniques, were not different in pregnant women who subsequently delivered a preterm neonate versus those who delivered at term. C1 [Romero, Roberto; Hassan, Sonia S.; Tarca, Adi L.; Bieda, Janine; Chaemsaithong, Piya; Miranda, Jezid; Chaiworapongsa, Tinnakorn] NIH, Perinatol Res Branch, Program Perinatal Res & Obstet, Div Intramural Res,Eunice Kennedy Shriver Natl In, Bethesda, MD 20892 USA. [Romero, Roberto] Univ Michigan, Dept Obstet & Gynaecol, Ann Arbor, MI 48109 USA. [Romero, Roberto] Michigan State Univ, Dept Epidemiol & Biostat, E Lansing, MI 48824 USA. [Hassan, Sonia S.; Chaiworapongsa, Tinnakorn] Wayne State Univ, Sch Med, Dept Obstet & Gynaecol, Detroit, MI 48201 USA. [Gajer, Pawel; Fadrosh, Douglas W.; Ravel, Jacques] Univ Maryland, Sch Med, Inst Genome Sci, Baltimore, MD 21201 USA. [Gajer, Pawel; Ravel, Jacques] Univ Maryland, Sch Med, Dept Microbiol & Immunol, Baltimore, MD 21201 USA. [Bieda, Janine; Chaiworapongsa, Tinnakorn] Hutzel Womens Hosp, Detroit Med Ctr, Detroit, MI 48201 USA. RP Romero, R (reprint author), NIH, Perinatol Res Branch, Program Perinatal Res & Obstet, Div Intramural Res,Eunice Kennedy Shriver Natl In, Bldg 10, Bethesda, MD 20892 USA. EM prbchiefstaff@med.wayne.edu; pgajer@gmail.com OI Ravel, Jacques/0000-0002-0851-2233 FU Eunice Kennedy Shriver National Institute of Child Health and Human Development, NIH, DHHS FX This work was funded, in part, by the Eunice Kennedy Shriver National Institute of Child Health and Human Development, NIH, DHHS. The authors wish to acknowledge the contributions of the patients who volunteered for these studies, the medical and healthcare personnel involved in the research effort, and colleagues who contributed to the discussions which eventually led to the conduct of the study. We are particularly grateful to Dr. Sharon Hillier of the University of Pittsburgh, Dr. Jack Sobel of Wayne State University, Dr. Ronald Lamont of the University of Southern Denmark, Dr. David Relman of Stanford University, Dr. Sorin Draghici of Wayne State University. NR 155 TC 47 Z9 47 U1 5 U2 11 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 2049-2618 J9 MICROBIOME JI Microbiome PD MAY 27 PY 2014 VL 2 AR 18 DI 10.1186/2049-2618-2-18 PG 15 WC Microbiology SC Microbiology GA CU0FT UT WOS:000363192200001 PM 24987521 ER PT J AU Kelsey, JS Geczy, T Lewin, NE Kedei, N Hill, CS Selezneva, JS Valle, CJ Woo, W Gorshkova, I Blumberg, PM AF Kelsey, Jessica S. Geczy, Tamas Lewin, Nancy E. Kedei, Noemi Hill, Colin S. Selezneva, Julia S. Valle, Christopher J. Woo, Wonhee Gorshkova, Inna Blumberg, Peter M. TI Charge Density Influences C1 Domain Ligand Affinity and Membrane Interactions SO CHEMBIOCHEM LA English DT Article DE diacylglycerols; ingenol 3-angelate; phorbol esters; protein kinase C ID PROTEIN-KINASE-C; NONPROMOTING 12-DEOXYPHORBOL 13-ESTERS; CONFORMATIONALLY CONSTRAINED ANALOGS; SITE-DIRECTED MUTAGENESIS; LATENT HIV-1 EXPRESSION; PROSTATE-CANCER CELLS; INGENOL MEBUTATE GEL; CD-1 MOUSE SKIN; PHORBOL ESTER; BRYOSTATIN 1 AB The C1 domain, which represents the recognition motif on protein kinase C for the lipophilic second messenger diacylglycerol and its ultrapotent analogues, the phorbol esters, has emerged as a promising therapeutic target for cancer and other indications. Potential target selectivity is markedly enhanced both because binding reflects ternary complex formation between the ligand, C1 domain, and phospholipid, and because binding drives membrane insertion of the C1 domain, permitting aspects of the C1 domain surface outside the binding site, per se, to influence binding energetics. Here, focusing on charged residues identified in atypical C1 domains which contribute to their loss of ligand binding activity, we showed that increasing charge along the rim of the binding cleft of the protein kinase C delta C1 b domain raises the requirement for anionic phospholipids. Correspondingly, it shifts the selectivity of C1 domain translocation to the plasma membrane, which is more negatively charged than internal membranes. This change in localization is most pronounced in the case of more hydrophilic ligands, which provide weaker membrane stabilization than do the more hydrophobic ligands and thus contributes an element to the structure-activity relations for C1 domain ligands. Coexpressing pairs of C1-containing constructs with differing charges each expressing a distinct fluorescent tag provided a powerful tool to demonstrate the effect of increasing charge in the C1 domain. C1 [Kelsey, Jessica S.; Geczy, Tamas; Lewin, Nancy E.; Kedei, Noemi; Hill, Colin S.; Selezneva, Julia S.; Valle, Christopher J.; Woo, Wonhee; Blumberg, Peter M.] NCI, Lab Canc Biol & Genet, Ctr Canc Res, Bethesda, MD 20892 USA. [Gorshkova, Inna] Natl Inst Biomed Imaging & Bioengn, Biomed Engn & Phys Sci Shared Resource Program, NIH, Bethesda, MD 20892 USA. RP Blumberg, PM (reprint author), NCI, Lab Canc Biol & Genet, Ctr Canc Res, Bldg 37,Room 4048 37 Convent Dr MSC 4255, Bethesda, MD 20892 USA. EM blumberp@dc37a.nci.nih.gov FU Intramural Research Program of the National Institutes of Health (NIH); Center for Cancer Research (CCR); National Cancer Institute (NCI) [Z1A BC 005270]; National Institute of Biomedical Imaging and Bioengineering (BEPS) FX This research was supported by the Intramural Research Program of the National Institutes of Health (NIH), Center for Cancer Research (CCR), National Cancer Institute (NCI; Z1A BC 005270), and the National Institute of Biomedical Imaging and Bioengineering (BEPS). Imaging was done in the CCR Confocal Microscopy Core Facility, NCI. NR 51 TC 2 Z9 2 U1 0 U2 8 PU WILEY-V C H VERLAG GMBH PI WEINHEIM PA BOSCHSTRASSE 12, D-69469 WEINHEIM, GERMANY SN 1439-4227 EI 1439-7633 J9 CHEMBIOCHEM JI ChemBioChem PD MAY 26 PY 2014 VL 15 IS 8 BP 1131 EP 1144 DI 10.1002/cbic.201400041 PG 14 WC Biochemistry & Molecular Biology; Chemistry, Medicinal SC Biochemistry & Molecular Biology; Pharmacology & Pharmacy GA AJ3QN UT WOS:000337582200011 PM 24777910 ER PT J AU Calleri, E Pochetti, G Dossou, KSS Laghezza, A Montanari, R Capelli, D Prada, E Loiodice, F Massolini, G Bernier, M Moaddel, R AF Calleri, Enrica Pochetti, Giorgio Dossou, Katina S. S. Laghezza, Antonio Montanari, Roberta Capelli, Davide Prada, Ellen Loiodice, Fulvio Massolini, Gabriella Bernier, Michel Moaddel, Ruin TI Resveratrol and Its Metabolites Bind to PPARs SO CHEMBIOCHEM LA English DT Article DE biochromatography; isothermal titration calorimetry; PPARs; resveratrol; transactivation assays; X-ray crystallography ID ACTIVATED RECEPTOR-GAMMA; FRONTAL AFFINITY-CHROMATOGRAPHY; CRYSTAL-STRUCTURE; ALPHA ACTIVATION; GENE-EXPRESSION; IN-VITRO; AGONISTS; MECHANISM; DOMAIN; DIFFERENTIATION AB Resveratrol, a modulator of several signaling proteins, can exert off-target effects involving the peroxisome proliferator-activated receptor (PPAR) transcription factors. However, evidence for the direct interaction between this polyphenol and PPARs is lacking. Here, we addressed the hypothesis that resveratrol and its metabolites control aspects of PPAR transcriptional activity through direct interaction with PPARs. Bioaffinity chromatographic studies with the immobilized ligand-binding domains (LBDs) of PPAR and PPAR and isothermal titration calorimetry allowed the binding affinities of resveratrol, resveratrol 3-O-glucuronide, resveratrol 4-O-glucuronide, and resveratrol 3-O-sulfate to both PPAR-LBDs to be determined. Interaction of resveratrol, resveratrol 3-O-glucuronide, and resveratrol 4-O-glucuronide with PPAR-LBD occurred with binding affinities of 1.4, 1.1, and 0.8 mu M, respectively, although only resveratrol bound to the PPAR alpha-LBD with a binding affinity of 2.7 mu M. Subsequently, X-ray crystallographic studies were carried out to characterize resveratrol binding to the PPAR gamma-LBD at the molecular level. The electron density map from the crystal structure of the complex between PPAR gamma-LBD and resveratrol revealed the presence of one molecule of resveratrol bound to the LBD of PPAR gamma, with the ligand occupying a position close to that of other known PPAR gamma ligands. Transactivation assays were also performed in HepG2 cells, with the results showing that resveratrol was not a PPAR agonist but instead was able to displace rosiglitazone from PPAR gamma and Wy-14643 from PPAR alpha with IC50 values of (27.4 +/- 1.8) mu M and (31.7 +/- 2.5) mu M, respectively. We propose that resveratrol acts as a PPAR antagonist through its direct interaction with PPAR gamma and PPAR alpha. C1 [Calleri, Enrica; Prada, Ellen; Massolini, Gabriella] Univ Pavia, Dipartimento Sci Farmaco, I-27100 Pavia, Italy. [Pochetti, Giorgio; Montanari, Roberta; Capelli, Davide] Consiglio Nazl Ric Montelibretti, Ist Cristallog, I-00015 Rome, Italy. [Dossou, Katina S. S.; Bernier, Michel; Moaddel, Ruin] NIA, Biomed Res Ctr, NIH, Baltimore, MD 21224 USA. [Laghezza, Antonio; Loiodice, Fulvio] Univ Bari Aldo Moro, Dipartimento Farm Sci Farmaco, I-70126 Bari, Italy. RP Moaddel, R (reprint author), NIA, Biomed Res Ctr, NIH, 251 Bayview Blvd,Suite 100, Baltimore, MD 21224 USA. EM moaddelru@grc.nia.nih.gov OI CALLERI, ENRICA/0000-0002-4246-460X; Bernier, Michel/0000-0002-5948-368X; Laghezza, Antonio/0000-0001-6221-6155 FU Intramural Research Program of the National Institute on Aging, National Institutes of Health; Ministero dell'Istruzione, dell'Universita e della Ricerca [PRIN 2009K7R7NA]; Ministero dell'Universita e della Ricerca Scientifica [2009Z8YTYC] FX This research was supported in part by the Intramural Research Program of the National Institute on Aging, National Institutes of Health (R.M.) and financial support from the Ministero dell'Istruzione, dell'Universita e della Ricerca (PRIN 2009K7R7NA to F.L.), and by a grant from the Ministero dell'Universita e della Ricerca Scientifica (grant no. 2009Z8YTYC to E.C.). There are no financial conflicts. NR 39 TC 16 Z9 17 U1 2 U2 23 PU WILEY-V C H VERLAG GMBH PI WEINHEIM PA BOSCHSTRASSE 12, D-69469 WEINHEIM, GERMANY SN 1439-4227 EI 1439-7633 J9 CHEMBIOCHEM JI ChemBioChem PD MAY 26 PY 2014 VL 15 IS 8 BP 1154 EP 1160 DI 10.1002/cbic.201300754 PG 7 WC Biochemistry & Molecular Biology; Chemistry, Medicinal SC Biochemistry & Molecular Biology; Pharmacology & Pharmacy GA AJ3QN UT WOS:000337582200013 PM 24796862 ER PT J AU Liu, RJ Dai, ZY Yeager, M Irizarry, RA Ritchie, ME AF Liu, Ruijie Dai, Zhiyin Yeager, Meredith Irizarry, Rafael A. Ritchie, Matthew E. TI KRLMM: an adaptive genotype calling method for common and low frequency variants SO BMC BIOINFORMATICS LA English DT Article DE Genotyping; Clustering; Microarray data analysis ID GENOME-WIDE ASSOCIATION; ALGORITHM; POPULATION; BEADCHIPS; RARE; MAP AB Background: SNP genotyping microarrays have revolutionized the study of complex disease. The current range of commercially available genotyping products contain extensive catalogues of low frequency and rare variants. Existing SNP calling algorithms have difficulty dealing with these low frequency variants, as the underlying models rely on each genotype having a reasonable number of observations to ensure accurate clustering. Results: Here we develop KRLMM, a new method for converting raw intensities into genotype calls that aims to overcome this issue. Our method is unique in that it applies careful between sample normalization and allows a variable number of clusters k (1, 2 or 3) for each SNP, where k is predicted using the available data. We compare our method to four genotyping algorithms (GenCall, GenoSNP, Illuminus and OptiCall) on several Illumina data sets that include samples from the HapMap project where the true genotypes are known in advance. All methods were found to have high overall accuracy (> 98%), with KRLMM consistently amongst the best. At low minor allele frequency, the KRLMM, OptiCall and GenoSNP algorithms were observed to be consistently more accurate than GenCall and Illuminus on our test data. Conclusions: Methods that tailor their approach to calling low frequency variants by either varying the number of clusters (KRLMM) or using information from other SNPs (OptiCall and GenoSNP) offer improved accuracy over methods that do not (GenCall and Illuminus). The KRLMM algorithm is implemented in the open-source crlmm package distributed via the Bioconductor project (http://www.bioconductor.org). C1 [Liu, Ruijie; Dai, Zhiyin; Ritchie, Matthew E.] Walter & Eliza Hall Inst Med Res, Mol Med Div, Parkville, Vic 3052, Australia. [Yeager, Meredith] NCI Frederick, Canc Genom Res Lab, SAIC Frederick Inc, Frederick, MD 20877 USA. [Irizarry, Rafael A.] Dana Farber Canc Inst, Dept Biostat & Computat Biol, Boston, MA 02215 USA. [Ritchie, Matthew E.] Univ Melbourne, Dept Math & Stat, Parkville, Vic 3010, Australia. [Ritchie, Matthew E.] Univ Melbourne, Dept Med Biol, Parkville, Vic 3010, Australia. RP Irizarry, RA (reprint author), Dana Farber Canc Inst, Dept Biostat & Computat Biol, CLSB 11007,450 Brookline Ave, Boston, MA 02215 USA. EM rafa@jimmy.harvard.edu; mritchie@wehi.edu.au OI Ritchie, Matthew/0000-0002-7383-0609 FU NHMRC [1050661]; Victorian State Government; Australian Government NHMRC IRIISS; NIH [R01GM083084] FX We thank Gordon Smyth for advice on regression analysis. This research was supported by NHMRC Project grant 1050661 (RL, MR), Victorian State Government Operational Infrastructure Support, Australian Government NHMRC IRIISS and NIH grant R01GM083084 (RI). NR 26 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 1471-2105 J9 BMC BIOINFORMATICS JI BMC Bioinformatics PD MAY 23 PY 2014 VL 15 AR 158 DI 10.1186/1471-2105-15-158 PG 11 WC Biochemical Research Methods; Biotechnology & Applied Microbiology; Mathematical & Computational Biology SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Mathematical & Computational Biology GA AK2IS UT WOS:000338243300001 PM 24886250 ER PT J AU Moktan, H Guiraldelli, MF Eyster, CA Zhao, WX Lee, CY Mather, T Camerini-Otero, RD Sung, P Zhou, DHH Pezza, RJ AF Moktan, Hem Guiraldelli, Michel F. Eyster, Craig A. Zhao, Weixing Lee, Chih-Ying Mather, Timothy Camerini-Otero, R. Daniel Sung, Patrick Zhou, Donghua H. Pezza, Roberto J. TI Solution Structure and DNA-binding Properties of the Winged Helix Domain of the Meiotic Recombination HOP2 Protein SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID NMR STRUCTURE DETERMINATION; CHROMOSOME SEGREGATION; HOP2-MND1 COMPLEX; OPERATOR COMPLEX; CHEMICAL-SHIFTS; MEIOSIS; MND1; INSIGHTS; REVEALS; RAD51 AB The HOP2 protein is required for efficient double-strand break repair which ensures the proper synapsis of homologous chromosomes and normal meiotic progression. We previously showed that in vitro HOP2 shows two distinctive activities: when it is incorporated into a HOP2-MND1 heterodimer, it stimulates DMC1 and RAD51 recombination activities, and the purified HOP2 alone is proficient in promoting strand invasion. The structural and biochemical basis of HOP2 action in recombination are poorly understood; therefore, they are the focus of this work. Herein, we present the solution structure of the amino-terminal portion of mouse HOP2, which contains a typical winged helix DNA-binding domain. Together with NMR spectral changes in the presence of double-stranded DNA, protein docking on DNA, and mutation analysis to identify the amino acids involved in DNA coordination, our results on the three-dimensional structure of HOP2 provide key information on the fundamental structural and biochemical requirements directing the interaction of HOP2 with DNA. These results, in combination with mutational experiments showing the role of a coiled-coil structural feature involved in HOP2 self-association, allow us to explain important aspects of the function of HOP2 in recombination. C1 [Moktan, Hem; Zhou, Donghua H.] Oklahoma State Univ, Dept Phys, Stillwater, OK 74078 USA. [Guiraldelli, Michel F.; Eyster, Craig A.; Lee, Chih-Ying; Pezza, Roberto J.] Oklahoma Med Res Fdn, Cell Cycle & Canc Biol Program, Oklahoma City, OK 73104 USA. [Zhao, Weixing; Sung, Patrick] Yale Univ, Sch Med, Dept Mol Biophys & Biochem, New Haven, CT 06520 USA. [Mather, Timothy] Oklahoma Med Res Fdn, Cardiovasc Biol Program, Oklahoma City, OK 73104 USA. [Mather, Timothy] Univ Oklahoma, Hlth Sci Ctr, Dept Biochem & Mol Biol, Oklahoma City, OK 73104 USA. [Camerini-Otero, R. Daniel] NIDDK, Genet & Biochem Branch, NIH, Bethesda, MD 20892 USA. [Pezza, Roberto J.] Univ Oklahoma, Hlth Sci Ctr, Dept Cell Biol, Oklahoma City, OK 73126 USA. RP Pezza, RJ (reprint author), Oklahoma Med Res Fdn, 825 NE 13th St, Oklahoma City, OK 73104 USA. EM Roberto-Pezza@omrf.org FU NIGMS, National Institutes of Health [1P20GM103636]; Oklahoma Center for the Advancement of Science and Technology Grant [HR10-48S]; National Institutes of Health [GM097713]; Oklahoma Center for the Advancement of Science and Technology [HR12-050] FX This work was supported by NIGMS, National Institutes of Health Award 1P20GM103636 and by Oklahoma Center for the Advancement of Science and Technology Grant HR10-48S (to R. J. P.). This work was also supported by National Institutes of Health Grant GM097713 (to D. H. Z.) and Oklahoma Center for the Advancement of Science and Technology Grant HR12-050 (to D. H. Z.). NR 43 TC 6 Z9 6 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 MAY 23 PY 2014 VL 289 IS 21 BP 14682 EP 14691 DI 10.1074/jbc.M114.548180 PG 10 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA AI9JE UT WOS:000337248100025 PM 24711446 ER PT J AU Peters, DE Szabo, R Friis, S Shylo, NA Sales, KU Holmbeck, K Bugge, TH AF Peters, Diane E. Szabo, Roman Friis, Stine Shylo, Natalia A. Sales, Katiuchia Uzzun Holmbeck, Kenn Bugge, Thomas H. TI The Membrane-anchored Serine Protease Prostasin (CAP1/PRSS8) Supports Epidermal Development and Postnatal Homeostasis Independent of Its Enzymatic Activity SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID MATRIPTASE-ACTIVATION; PROTEOLYTIC CASCADE; BARRIER FUNCTION; MUTATIONS; DIFFERENTIATION; CHANNELS; CLOSURE; MICE; CELL AB The membrane-anchored serine protease prostasin (CAP1/PRSS8) is part of a cell surface proteolytic cascade that is essential for epithelial barrier formation and homeostasis. Here, we report the surprising finding that prostasin executes these functions independent of its own enzymatic activity. Prostasin null (Prss8(-/-)) mice lack barrier formation and display fatal postnatal dehydration. In sharp contrast, mice homozygous for a point mutation in the Prss8 gene, which causes the substitution of the active site serine within the catalytic histidine-aspartate-serine triad with alanine and renders prostasin catalytically inactive (Prss8(Cat-/Cat-) mice), develop barrier function and are healthy when followed for up to 20 weeks. This striking difference could not be explained by genetic modifiers or by maternal effects, as these divergent phenotypes were displayed by Prss8(-/-) and Prss8Cat(-/Cat-) mice born within the same litter. Furthermore, Prss8Cat(-/Cat-) mice were able to regenerate epidermal covering following cutaneous wounding. This study provides the first demonstration that essential in vivo functions of prostasin are executed by a non-enzymatic activity of this unique membrane-anchored serine protease. C1 [Peters, Diane E.; Szabo, Roman; Friis, Stine; Shylo, Natalia A.; Sales, Katiuchia Uzzun; Bugge, Thomas H.] Natl Inst Dent & Craniofacial Res, Proteases & Tissue Remodeling Sect, Oral & Pharyngeal Canc Branch, NIH, Bethesda, MD 20892 USA. [Peters, Diane E.] Tufts Univ, Sch Med, Program Pharmacol & Expt Therapeut, Boston, MA 02111 USA. [Friis, Stine] Univ Copenhagen, Dept Cellular & Mol Med, Fac Hlth Sci, DK-2200 Copenhagen, Denmark. [Holmbeck, Kenn] Natl Inst Dent & Craniofacial Res, Connect Tissue Remodeling Sect, NIH, Bethesda, MD 20892 USA. [Sales, Katiuchia Uzzun] Natl Inst Dent & Craniofacial Res, Clin Res Core, NIH, Bethesda, MD 20892 USA. RP Bugge, TH (reprint author), Natl Inst Dent & Craniofacial Res, Proteases & Tissue Remodeling Sect, Oral & Pharyngeal Canc Branch, NIH, 30 Convent Dr,Rm 211, Bethesda, MD 20892 USA. EM thomas.bugge@nih.gov FU NIDCR Intramural Research Program; Harboe Foundation; Lundbeck Foundation; Foundation of 17.12.1981 FX This work was supported by the NIDCR Intramural Research Program (to K. H. and T. H. B.), by The Harboe Foundation, The Lundbeck Foundation, and the Foundation of 17.12.1981 (to S. F.). NR 24 TC 11 Z9 11 U1 0 U2 1 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 EI 1083-351X J9 J BIOL CHEM JI J. Biol. Chem. PD MAY 23 PY 2014 VL 289 IS 21 BP 14740 EP 14749 DI 10.1074/jbc.M113.541318 PG 10 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA AI9JE UT WOS:000337248100030 PM 24706745 ER PT J AU Kohler, D Devanathan, V Franz, CBD Eldh, T Novakovic, A Roth, JM Granja, T Birnbaumer, L Rosenberger, P Beer-Hammer, S Nurnberg, B AF Koehler, David Devanathan, Vasudharani Franz, Claudia Bernardo de Oliveira Eldh, Therese Novakovic, Ana Roth, Judith M. Granja, Tiago Birnbaumer, Lutz Rosenberger, Peter Beer-Hammer, Sandra Nuernberg, Bernd TI G alpha(i2)- and G alpha(i3)- Deficient Mice Display Opposite Severity of Myocardial Ischemia Reperfusion Injury SO PLOS ONE LA English DT Article ID G-PROTEIN; PERTUSSIS TOXIN; DISEASE; CARDIOMYOCYTES; INHIBITION; MIGRATION; CYCLASE; HEART AB G-protein-coupled receptors (GPCRs) are the most abundant receptors in the heart and therefore are common targets for cardiovascular therapeutics. The activated GPCRs transduce their signals via heterotrimeric G-proteins. The four major families of G-proteins identified so far are specified through their alpha-subunit: G alpha(i), G alpha(s), G alpha(q) and G(12/13). G alpha(i)-proteins have been reported to protect hearts from ischemia reperfusion injury. However, determining the individual impact of G alpha(i2) or G alpha(i3) on myocardial ischemia injury has not been clarified yet. Here, we first investigated expression of G alpha(i2) and G alpha(i3) on transcriptional level by quantitative PCR and on protein level by immunoblot analysis as well as by immunofluorescence in cardiac tissues of wild-type, G alpha(i2), and G alpha(i3)-deficient mice. G alpha(i2) was expressed at higher levels than G alpha(i3) in murine hearts, and irrespective of the isoform being knocked out we observed an up regulation of the remaining G alpha i-protein. Myocardial ischemia promptly regulated cardiac mRNA and with a slight delay protein levels of both G alpha(i2) and G alpha(i3), indicating important roles for both G alpha(i) isoforms. Furthermore, ischemia reperfusion injury in G alpha(i2)- and G alpha(i3)-deficient mice exhibited opposite outcomes. Whereas the absence of G alpha(i2) significantly increased the infarct size in the heart, the absence of G alpha(i3) or the concomitant upregulation of G alpha(i2) dramatically reduced cardiac infarction. In conclusion, we demonstrate for the first time that the genetic ablation of G alpha(i) proteins has protective or deleterious effects on cardiac ischemia reperfusion injury depending on the isoform being absent. C1 [Koehler, David; Franz, Claudia Bernardo de Oliveira; Roth, Judith M.; Granja, Tiago; Rosenberger, Peter] Eberhard Karls Univ Hosp & Clin, Dept Anesthesiol & Intens Care Med, Inst Expt & Clin Pharmacol & Toxicol, Tubingen, Germany. [Koehler, David; Devanathan, Vasudharani; Franz, Claudia Bernardo de Oliveira; Eldh, Therese; Novakovic, Ana; Roth, Judith M.; Granja, Tiago; Rosenberger, Peter; Beer-Hammer, Sandra; Nuernberg, Bernd] Interfac Ctr Pharmacogen & Drug Res, Tubingen, Germany. [Devanathan, Vasudharani; Eldh, Therese; Novakovic, Ana; Beer-Hammer, Sandra; Nuernberg, Bernd] Eberhard Karls Univ Hosp & Clin, Inst Expt & Clin Pharmacol & Toxicol, Dept Pharmacol & Expt Therapy, Tubingen, Germany. [Birnbaumer, Lutz] NIEHS, Neurobiol Lab, Div Intramural Res, NIH,Dept Hlth & Human Serv, Res Triangle Pk, NC 27709 USA. RP Beer-Hammer, S (reprint author), Eberhard Karls Univ Hosp & Clin, Inst Expt & Clin Pharmacol & Toxicol, Dept Pharmacol & Expt Therapy, Tubingen, Germany. EM sandra.beer-hammer@uni-tuebingen.de; bernd.nuernberg@uni-tuebingen.de FU Deutsche Forschungsgemeinschaft [SFB 612, MO2252/1]; Tuebingen University; NIH [Z01-ES-101643] FX This work was supported by grants of the Deutsche Forschungsgemeinschaft (SFB 612 to B.N. and MO2252/1 to D. K.), the Open Access Publishing Fund of Tuebingen University and the Intramural Research Program of the NIH (project Z01-ES-101643 to L. B.). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 29 TC 9 Z9 9 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 MAY 23 PY 2014 VL 9 IS 5 AR e98325 DI 10.1371/journal.pone.0098325 PG 8 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA AI4ML UT WOS:000336839400066 PM 24858945 ER PT J AU Paoletta, S Tosh, DK Salvemini, D Jacobson, KA AF Paoletta, Silvia Tosh, Dilip K. Salvemini, Daniela Jacobson, Kenneth A. TI Structural Probing of Off-Target G Protein-Coupled Receptor Activities within a Series of Adenosine/Adenine Congeners SO PLOS ONE LA English DT Article ID SEROTONIN RECEPTORS; DRUG DESIGN; NUCLEOSIDES; AGONISTS; 2-ARYLETHYNYL; SUBSTITUTIONS; PROMISCUITY; SELECTIVITY; ANTAGONISTS; ACTIVATION AB We studied patterns of off-target receptor interactions, mostly at G protein-coupled receptors (GPCRs) in the mu M range, of nucleoside derivatives that are highly engineered for nM interaction with adenosine receptors (ARs). Because of the considerable interest of using AR ligands for treating diseases of the CNS, we used the Psychoactive Drug Screening Program (PDSP) for probing promiscuity of these adenosine/adenine congeners at 41 diverse receptors, channels and a transporter. The step-wise truncation of rigidified, trisubstituted (at N degrees, C2, and 5' positions) nucleosides revealed unanticipated interactions mainly with biogenic amine receptors, such as adrenergic receptors and serotonergic receptors, with affinities as high as 61 nM. The unmasking of consistent sets of structure activity relationship (SAR) at novel sites suggested similarities between receptor families in molecular recognition. Extensive molecular modeling of the GPCRs affected suggested binding modes of the ligands that supported the patterns of SAR at individual receptors. In some cases, the ligand docking mode closely resembled AR binding and in other cases the ligand assumed different orientations. The recognition patterns for different GPCRs were clustered according to which substituent groups were tolerated and explained in light of the complementarity with the receptor binding site. Thus, some likely off-target interactions, a concern for secondary drug effects, can be predicted for analogues of this set of substructures, aiding the design of additional structural analogues that either eliminate or accentuate certain off-target activities. Moreover, similar analyses could be performed for unrelated structural families for other GPCRs. C1 [Paoletta, Silvia; Tosh, Dilip K.; Jacobson, Kenneth A.] NIDDK, Mol Recognit Sect, Bioorgan Chem Lab, NIH, Bethesda, MD 20892 USA. [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, 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 (Intramural Research Program of the NIDDK); National Institutes of Health [R01HL077707] FX This research was supported by the National Institutes of Health (Intramural Research Program of the NIDDK and R01HL077707). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 40 TC 12 Z9 12 U1 0 U2 3 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA SN 1932-6203 J9 PLOS ONE JI PLoS One PD MAY 23 PY 2014 VL 9 IS 5 AR e97858 DI 10.1371/journal.pone.0097858 PG 14 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA AI4ML UT WOS:000336839400028 PM 24859150 ER PT J AU Xiong, Y Zhang, LS Kebebew, E AF Xiong, Yin Zhang, Lisa Kebebew, Electron TI MiR-20a Is Upregulated in Anaplastic Thyroid Cancer and Targets LIMK1 SO PLOS ONE LA English DT Article ID BREAST-CANCER; MIR-17-92 CLUSTER; TUMOR-METASTASIS; PROSTATE-CANCER; CELL-LINE; MICRORNA; INVASION; EXPRESSION; KINASE; PROLIFERATION AB Background: There have been conflicting reports regarding the function of miR-20a in a variety of cancer types and we previously found it to be dysregulated in sporadic versus familial papillary thyroid cancer. In this study, we studied the expression of miR-20a in normal, benign and malignant thyroid samples, and its effect on thyroid cancer cells in vitro and in vivo. Methodology/Principal Findings: The expression of miR-20a in normal, benign and malignant thyroid tissue was determined by quantitative RT-PCR. Thyroid cancer cells were transfected with miR-20a and the effect on cellular proliferation, tumor spheroid formation, and invasion was evaluated. Target genes of miR-20 were determined by genome-wide mRNA expression analysis with miR-20a overexpression in thyroid cancer cells and target prediction database. Target genes were validated by quantitative PCR and immunoblotting, and luciferase assays. MiR-20a expression was significantly higher in anaplastic thyroid cancer than in differentiated thyroid cancer, and benign and normal thyroid tissues. MiR-20a significantly inhibited thyroid cancer cell proliferation in vitro (p<0.01) and in vivo (p<0.01), tumor spheroid formation (p<0.05) and invasion (p<0.05) in multiple thyroid cancer cell lines. We found that LIMK1 was a target of miR-20a in thyroid cancer cell lines and direct knockdown of LIMK1 recapitulated the effect of miR-20a in thyroid cancer cells. Conclusions/Significance: To our knowledge, this is the first study to demonstrate that miR-20a plays a role as a tumor suppressor in thyroid cancer cells and targets LIMK1. Our findings suggest the upregulated expression of miR-20a in anaplastic thyroid cancer counteracts thyroid cancer progression and may have therapeutic potential. C1 [Xiong, Yin; Zhang, Lisa; Kebebew, Electron] NCI, Endocrine Oncol Branch, Ctr Canc Res, Bethesda, MD 20892 USA. RP Kebebew, E (reprint author), NCI, Endocrine Oncol Branch, Ctr Canc Res, Bethesda, MD 20892 USA. EM kebebewe@mail.nih.gov FU National Institutes of Health, National Cancer Institute FX This work was funded by the National Institutes of Health, National Cancer Institute. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 34 TC 22 Z9 22 U1 0 U2 2 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA SN 1932-6203 J9 PLOS ONE JI PLoS One PD MAY 23 PY 2014 VL 9 IS 5 AR e96103 DI 10.1371/journal.pone.0096103 PG 10 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA AI4ML UT WOS:000336839400001 PM 24858712 ER PT J AU Gromowski, GD Firestone, CY Hanson, CT Whitehead, SS AF Gromowski, Gregory D. Firestone, Cai-Yen Hanson, Christopher T. Whitehead, Stephen S. TI Japanese encephalitis virus vaccine candidates generated by chimerization with dengue virus type 4 SO VACCINE LA English DT Article DE Japanese encephalitis virus; Chimeric virus; Live-attenuated vaccine ID ANTIBODY-MEDIATED NEUTRALIZATION; RHESUS-MONKEYS; PHYLOGENETIC ANALYSIS; PROTECTIVE EFFICACY; CAPSID PROTEIN; CORE PROTEIN; FLAVIVIRUS; IMMUNOGENICITY; CLEAVAGE; REPLICATION AB Japanese encephalitis virus (JEV) is a leading cause of viral encephalitis worldwide and vaccination is one of the most effective ways to prevent disease. A suitable live-attenuated JEV vaccine could be formulated with a live-attenuated tetravalent dengue vaccine for the control of these viruses in endemic areas. Toward this goal, we generated chimeric virus vaccine candidates by replacing the precursor membrane (prM) and envelope (E) protein structural genes of recombinant dengue virus type 4 (rDEN4) or attenuated vaccine candidate rDEN4 Delta 30 with those of wild-type JEV strain India/78. Mutations were engineered in E, NS3 and NS4B protein genes to improve replication in Vero cells. The chimeric viruses were attenuated in mice and some elicited modest but protective levels of immunity after a single dose. One particular chimeric virus, bearing E protein mutation Q264H, replicated to higher titer in tissue culture and was significantly more immunogenic in mice. The results are compared with live-attenuated JEV vaccine strain SA14-14-2. Published by Elsevier Ltd. C1 [Gromowski, Gregory D.; Firestone, Cai-Yen; Hanson, Christopher T.; Whitehead, Stephen S.] NIAID, Infect Dis Lab, NIH, Bethesda, MD 20892 USA. RP Gromowski, GD (reprint author), NIAID, Infect Dis Lab, NIH, Bethesda, MD 20892 USA. EM gromowskig@niaid.nih.gov FU National Institute of Allergy and Infectious Diseases Intramural Research Program; National Institutes of Health FX We would like to thank the NIAID Comparative Medicine Branch for assisting with animal studies, Dr. Jose Bustos-Arriaga for assisting with flow cytometry, and Drs. Ted Pierson and Kim Dowd for supplying reagents and expertise for the RVP assay. This work was supported by the National Institute of Allergy and Infectious Diseases Intramural Research Program, National Institutes of Health. NR 49 TC 6 Z9 6 U1 0 U2 3 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0264-410X EI 1873-2518 J9 VACCINE JI Vaccine PD MAY 23 PY 2014 VL 32 IS 25 BP 3010 EP 3018 DI 10.1016/j.vaccine.2014.03.062 PG 9 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA AI2UG UT WOS:000336713000015 PM 24699473 ER PT J AU Weisz, A Ridge, CD Roque, JA Mazzola, EP Ito, Y AF Weisz, Adrian Ridge, Clark D. Roque, Jose A. Mazzola, Eugene P. Ito, Yoichiro TI Preparative separation of two subsidiary colors of FD&C Yellow No. 5 (Tartrazine) using spiral high-speed counter-current chromatography SO JOURNAL OF CHROMATOGRAPHY A LA English DT Article DE Spiral high-speed counter-current chromatography; Highly polar organic/high-ionic strength aqueous two-phase solvent systems; FD&C Yellow No. 5; Tartrazine; Subsidiary colors; NMR ID TUBING SUPPORT ROTOR; ACID-BASE EQUILIBRIA; QUINOLINE YELLOW; AZO-HYDRAZONE; PURIFICATION; COMPONENTS; SYSTEMS; DYES; SALT AB Specifications in the U.S. Code of Federal Regulations for the color additive FD&C Yellow No. 5 (Color Index No. 19140) limit the level of the tetrasodium salt of 4-[(4',5-disulfo[1,1'-biphenyl]-2-yl)hydrazono]-4,5-dihydro-5-oxo-1-(4-sulfophenyl)-1H-pyrazole-3-carboxylic acid and that of the trisodium salt of 4,4'-[4,5-dihydro-5-oxo-4-[(4-sulfophenyl)hydrazono]-1H-pyrazol-1,3-diyl]bis[benzenesulfonic acid], which are subsidiary colors abbreviated as Pk5 and Pk7, respectively. Small amounts of Pk5 and Pk7 are needed by the U.S. Food and Drug Administration for confirmatory analyses and for development of analytical methods. The present study describes the use of spiral high-speed counter-current chromatography (HSCCC) to separate the closely related minor components Pk5 and Pk7 from a sample of FD&C Yellow No. 5 containing similar to 3.5% Pk5 and similar to 0.7% Pk7. The separations were performed with highly polar organic/high-ionic strength aqueous two-phase solvent systems that were chosen by applying the recently introduced method known as graphic optimization of partition coefficients (Zeng et al., 2013). Multiple similar to 1.0 g portions of FD&C Yellow No. 5 (totaling 6.4g dye) were separated, using the upper phase of the solvent system 1-butanol/abs. ethanol/saturated ammonium sulfate/water, 1.7:0.3:1:1, v/v/v/v, as the mobile phase. After removing the ammonium sulfate from the HSCCC-collected fractions, these separations resulted in an enriched dye mixture (similar to 160 mg) of which Pk5 represented similar to 46% and Pk7, similar to 21%. Separation of the enriched mixture, this time using the lower phase of that solvent system as the mobile phase, resulted in 61 mg of Pk5 collected in fractions whose purity ranged from 88.0% to 92.7%. Pk7 (20.7 mg, similar to 83% purity) was recovered from the upper phase of the column contents. Application of this procedure also resulted in purifying the major component of FD&C Yellow No. 5 to >99% purity. The separated compounds were characterized by high-resolution mass spectrometry and several H-1 and C-13 nuclear magnetic resonance spectroscopic techniques. Published by Elsevier B.V. C1 [Weisz, Adrian; Roque, Jose A.] US FDA, Off Cosmet & Colors, Ctr Food Safety & Appl Nutr, College Pk, MD 20740 USA. [Ridge, Clark D.; Mazzola, Eugene P.] US FDA, Off Regulatory Sci, Ctr Food Safety & Appl Nutr, College Pk, MD 20740 USA. [Ito, Yoichiro] NHLBI, Lab Bioseparat Technol, Biochem & Biophys Ctr, NIH, Bethesda, MD 20892 USA. RP Weisz, A (reprint author), US FDA, Off Cosmet & Colors, Ctr Food Safety & Appl Nutr, College Pk, MD 20740 USA. EM adrian.weisz@fda.hhs.gov FU Intramural NIH HHS [ZIA HL005107-06] NR 37 TC 7 Z9 7 U1 6 U2 35 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 MAY 23 PY 2014 VL 1343 BP 91 EP 100 DI 10.1016/j.chroma.2014.03.059 PG 10 WC Biochemical Research Methods; Chemistry, Analytical SC Biochemistry & Molecular Biology; Chemistry GA AH5UE UT WOS:000336195800012 PM 24755184 ER PT J AU Raj, DK Nixon, CP Nixon, CE Dvorin, JD DiPetrillo, CG Pond-Tor, S Wu, HW Jolly, G Pischel, L Lu, AL Michelow, IC Cheng, L Conteh, S McDonald, EA Absalon, S Holte, SE Friedman, JF Fried, M Duffy, PE Kurtis, JD AF Raj, Dipak K. Nixon, Christian P. Nixon, Christina E. Dvorin, Jeffrey D. DiPetrillo, Christen G. Pond-Tor, Sunthorn Wu, Hai-Wei Jolly, Grant Pischel, Lauren Lu, Ailin Michelow, Ian C. Cheng, Ling Conteh, Solomon McDonald, Emily A. Absalon, Sabrina Holte, Sarah E. Friedman, Jennifer F. Fried, Michal Duffy, Patrick E. Kurtis, Jonathan D. TI Antibodies to PfSEA-1 block parasite egress from RBCs and protect against malaria infection SO SCIENCE LA English DT Article ID PLASMODIUM-FALCIPARUM; HUMAN RESISTANCE; ERYTHROCYTES; INVASION; VACCINE; GROWTH AB Novel vaccines are urgently needed to reduce the burden of severe malaria. Using a differential whole-proteome screening method, we identified Plasmodium falciparum schizont egress antigen-1 (PfSEA-1), a 244-kilodalton parasite antigen expressed in schizont-infected red blood cells (RBCs). Antibodies to PfSEA-1 decreased parasite replication by arresting schizont rupture, and conditional disruption of PfSEA-1 resulted in a profound parasite replication defect. Vaccination of mice with recombinant Plasmodium berghei PbSEA-1 significantly reduced parasitemia and delayed mortality after lethal challenge with the Plasmodium berghei strain ANKA. Tanzanian children with antibodies to recombinant PfSEA-1A (rPfSEA-1A) did not experience severe malaria, and Kenyan adolescents and adults with antibodies to rPfSEA-1A had significantly lower parasite densities than individuals without these antibodies. By blocking schizont egress, PfSEA-1 may synergize with other vaccines targeting hepatocyte and RBC invasion. C1 [Raj, Dipak K.; Nixon, Christian P.; Nixon, Christina E.; Pond-Tor, Sunthorn; Wu, Hai-Wei; Pischel, Lauren; Lu, Ailin; Michelow, Ian C.; Cheng, Ling; McDonald, Emily A.; Friedman, Jennifer F.; Kurtis, Jonathan D.] Brown Univ, Rhode Isl Hosp, Warren Alpert Med Sch, Ctr Int Hlth Res, Providence, RI 02903 USA. [Dvorin, Jeffrey D.; DiPetrillo, Christen G.; Absalon, Sabrina] Boston Childrens Hosp, Div Infect Dis, Boston, MA 02115 USA. [Dvorin, Jeffrey D.; DiPetrillo, Christen G.; Absalon, Sabrina] Harvard Univ, Sch Med, Boston, MA 02115 USA. [Wu, Hai-Wei; Michelow, Ian C.; Friedman, Jennifer F.] Brown Univ, Rhode Isl Hosp, Warren Alpert Med Sch, Dept Pediat, Providence, RI 02903 USA. [Jolly, Grant; Kurtis, Jonathan D.] Brown Univ, Warren Alpert Med Sch, Rhode Isl Hosp, Dept Pathol & Lab Med, Providence, RI 02906 USA. [Conteh, Solomon; Fried, Michal; Duffy, Patrick E.] NIAID, Lab Malaria Immunol & Vaccinol, NIH, Rockville, MD 20892 USA. [Holte, Sarah E.] Univ Washington, Fred Hutchinson Canc Res Ctr, Program Biostat & Biomath, Dept Biostat & Global Hlth, Seattle, WA 98109 USA. RP Kurtis, JD (reprint author), Brown Univ, Rhode Isl Hosp, Warren Alpert Med Sch, Ctr Int Hlth Res, Providence, RI 02903 USA. EM jonathan_kurtis@brown.edu OI Absalon, Sabrina/0000-0002-4167-3071; Friedman, Jennifer/0000-0001-5804-9921 FU U.S. National Institutes of Health (NIH) [R01-AI52059]; Bill & Melinda Gates Foundation [1364]; Intramural Research Program of the National Institute of Allergy and Infectious Diseases-NIH; NIH [R01-AI076353, R01-AI102907, DP2-AI112219, T32-DA013911, 1K08AI100997-01A1]; internal Lifespan Hospital System Research Pilot Award Grant FX The authors thank the Mother Offspring Malaria Study project staff for their efforts in collecting clinical data, processing samples, and interpreting malaria blood smears, as well as the study participants and their families. Ethical clearance was obtained from the institutitional review boards of the Seattle Biomedical Research Institute and Rhode Island Hospital; the Medical Research Coordinating Committee of the National Institute for Medical Research, Tanzania; and the Kenyan Medical Research Institute. We thank A. Muehlenbachs for assistance in interpreting the electron microscopy images, B. Morrison for assistance with data management, and D. Lanar for the LSA proteins. This work was supported by grants from the U.S. National Institutes of Health (NIH) (grant R01-AI52059) and the Bill & Melinda Gates Foundation (grant 1364) to P. E. D., the Intramural Research Program of the National Institute of Allergy and Infectious Diseases-NIH, and grants from NIH (grant R01-AI076353) and an internal Lifespan Hospital System Research Pilot Award Grant to J.D.K., and grants from NIH to J.D.D. (R01-AI102907 and DP2-AI112219). C.E.N. (grant T32-DA013911) and I.C.M. (grant 1K08AI100997-01A1) were supported by NIH. We also acknowledge research core services provided by the Rhode Island Hospital imaging core (G. Hovanesian) and core services supported by Lifespan/Tufts/Brown Center for Aids Research (P30AI042853) and Center for Biomedical Research Excellence (P20GM103421). The DNA sequence for PfSEA-1 is available in PlasmoDB (www.Plasmodb.org) as ID no. PF3D7_1021800. The work presented in this manuscript has been submitted in partial support of patent application PCT/US12/67404 filed with the U.S. Patent Office. J.D.K., J.F.F., M.F., and P.E.D. designed the study; J.D.K., D.K.R., J.F.F., M. F., and P. E. D. drafted the manuscript; M. F. and P. E. D. conducted the field-based sample and epidemiologic data collection; C.P.N. conducted the differential screening; D. K. R, L. P., A. L., C.E.N., and L. C. performed the in vitro growth assays; D. K. R. and G.J. performed the immunolocalization; D. K. R. performed the gene knockout studies; C. G. D., E. A. M., S. A., and J.D.D. performed the conditional gene knockdown studies; I. C. M. performed the single-nucleotide polymorphism detection; S.P.-T., L.C., and H.-W.W. performed the antibody detection assays; S.P.-T. expressed and purified rPf SEA-1A and rPbSEA-1A; D.K.R., C.E.N., and S. C. performed the vaccination studies; J.F.F., J.D.K., and S.E.H. performed the statistical analyses; and J.D.K., J.F.F., M.F., and P.E.D. supervised the study. The authors declare no competing financial interests. NR 26 TC 29 Z9 29 U1 1 U2 20 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 MAY 23 PY 2014 VL 344 IS 6186 BP 871 EP 877 DI 10.1126/science.1254417 PG 7 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA AH6IL UT WOS:000336233800040 PM 24855263 ER PT J AU Wiestner, A AF Wiestner, Adrian TI Predicting treatment outcomes in CLL SO BLOOD LA English DT Editorial Material ID CHRONIC LYMPHOCYTIC-LEUKEMIA; MUTATIONS; NOTCH1; TRIAL; SF3B1 C1 NIH, Bethesda, MD 20892 USA. RP Wiestner, A (reprint author), NIH, Bethesda, MD 20892 USA. NR 10 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 MAY 22 PY 2014 VL 123 IS 21 BP 3212 EP 3214 DI 10.1182/blood-2014-04-565325 PG 5 WC Hematology SC Hematology GA AQ2LA UT WOS:000342616300002 PM 24855188 ER PT J AU Herman, SEM Mustafa, RZ Gyamfi, JA Pittaluga, S Chang, S Chang, B Farooqui, M Wiestner, A AF Herman, Sarah E. M. Mustafa, Rashida Z. Gyamfi, Jennifer A. Pittaluga, Stefania Chang, Stella Chang, Betty Farooqui, Mohammed Wiestner, Adrian TI Ibrutinib inhibits BCR and NF-kappa B signaling and reduces tumor proliferation in tissue-resident cells of patients with CLL SO BLOOD LA English DT Article ID CHRONIC LYMPHOCYTIC-LEUKEMIA; TYROSINE KINASE BTK; IN-VIVO; TARGETING BTK; OPEN-LABEL; LYMPHOMA; ACTIVATION; PCI-32765; THERAPY; MALIGNANCIES AB Chronic lymphocytic leukemia (CLL) cells depend on microenvironmental factors for proliferation and survival. In particular, tissue-resident CLL cells show prominent activation of both B-cell receptor (BCR) and NF-kappa B pathways. We evaluated the in vivo effects of ibrutinib, a Bruton tyrosine kinase (BTK) inhibitor on tumor cell activation and proliferation in the blood, lymph node, and bone marrow of patients with CLL. Applying validated pathway-specific gene signatures, we detected a rapid and sustained downregulation of BCR and NF-kappa B signaling in CLL cells from both the peripheral blood and tissue compartments during ibrutinib treatment. Ibrutinib reduced phosphorylation of PLC gamma 2 and ERK and decreased nuclear protein expression of NF-kappa B p50. Ibrutinib significantly decreased tumor proliferation and expression of surface activation markers CD69 and CD86, independent of prognostic factors such as IGHV mutational status, chromosome 17p deletion, or prior treatment history. Interestingly, stronger inhibition of BCR signaling in lymph node resident CLL cells after one dose of ibrutinib was associated with a higher rate of nodal response at the end of cycle 2. Together, these data validate on-target effects of BTK inhibition in the tissue compartments and demonstrate that ibrutinib effectively inhibits pathways that promote tumor cell activation and proliferation in vivo. This study is registered at www.clinicaltrials.gov as #NCT01500733. C1 [Herman, Sarah E. M.; Mustafa, Rashida Z.; Gyamfi, Jennifer A.; Farooqui, Mohammed; Wiestner, Adrian] NHLBI, Hematol Branch, Bethesda, MD 20892 USA. [Pittaluga, Stefania] NCI, Pathol Lab, NIH, Bethesda, MD 20892 USA. [Chang, Stella; Chang, Betty] Pharmacyclics Inc, Sunnyvale, CA USA. RP Wiestner, A (reprint author), NHLBI, Hematol Branch, NIH, Bldg 10,CRC 3-5140,10 Ctr Dr, Bethesda, MD 20892 USA. EM adrian.wiestner@nih.gov FU Intramural Research Program, the National, Heart, Lung and Blood Institute, the National Institutes of Health FX This work was supported by the Intramural Research Program, the National, Heart, Lung and Blood Institute, the National Institutes of Health. NR 49 TC 63 Z9 64 U1 0 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 MAY 22 PY 2014 VL 123 IS 21 BP 3286 EP 3295 DI 10.1182/blood-2014-02-548610 PG 10 WC Hematology SC Hematology GA AQ2LA UT WOS:000342616300015 PM 24659631 ER PT J AU Hollingshead, MG Stockwin, LH Alcoser, SY Newton, DL Orsburn, BC Bonomi, CA Borgel, SD Divelbiss, R Dougherty, KM Hager, EJ Holbeck, SL Kaur, G Kimmel, DJ Kunkel, MW Millione, A Mullendore, ME Stotler, H Collins, J AF Hollingshead, Melinda G. Stockwin, Luke H. Alcoser, Sergio Y. Newton, Dianne L. Orsburn, Benjamin C. Bonomi, Carrie A. Borgel, Suzanne D. Divelbiss, Raymond Dougherty, Kelly M. Hager, Elizabeth J. Holbeck, Susan L. Kaur, Gurmeet Kimmel, David J. Kunkel, Mark W. Millione, Angelena Mullendore, Michael E. Stotler, Howard Collins, Jerry TI Gene expression profiling of 49 human tumor xenografts from in vitro culture through multiple in vivo passages - strategies for data mining in support of therapeutic studies SO BMC GENOMICS LA English DT Article DE Xenograft models; Affymetrix HG-U133 Plus 2.0 array; cDNA microarray; NCI-60 cell line screen; Transcriptomic stability; Transcriptomic expression; in vitro to in vivo transition ID CELL-LINES; MESSENGER-RNA; CANCER CELLS; CHEMOSENSITIVITY; MICROARRAYS; RESISTANCE; MIGRATION; INVASION; PATHWAY; GROWTH AB Background: Development of cancer therapeutics partially depends upon selection of appropriate animal models. Therefore, improvements to model selection are beneficial. Results: Forty-nine human tumor xenografts at in vivo passages 1, 4 and 10 were subjected to cDNA microarray analysis yielding a dataset of 823 Affymetrix HG-U133 Plus 2.0 arrays. To illustrate mining strategies supporting therapeutic studies, transcript expression was determined: 1) relative to other models, 2) with successive in vivo passage, and 3) during the in vitro to in vivo transition. Ranking models according to relative transcript expression in vivo has the potential to improve initial model selection. For example, combining p53 tumor expression data with mutational status could guide selection of tumors for therapeutic studies of agents where p53 status purportedly affects efficacy (e.g., MK-1775). The utility of monitoring changes in gene expression with extended in vivo tumor passages was illustrated by focused studies of drug resistance mediators and receptor tyrosine kinases. Noteworthy observations included a significant decline in HCT-15 colon xenograft ABCB1 transporter expression and increased expression of the kinase KIT in A549 with serial passage. These trends predict sensitivity to agents such as paclitaxel (ABCB1 substrate) and imatinib (c-KIT inhibitor) would be altered with extended passage. Given that gene expression results indicated some models undergo profound changes with in vivo passage, a general metric of stability was generated so models could be ranked accordingly. Lastly, changes occurring during transition from in vitro to in vivo growth may have important consequences for therapeutic studies since targets identified in vitro could be over-or under-represented when tumor cells adapt to in vivo growth. A comprehensive list of mouse transcripts capable of cross-hybridizing with human probe sets on the HG-U133 Plus 2.0 array was generated. Removal of the murine artifacts followed by pairwise analysis of in vitro cells with respective passage 1 xenografts and GO analysis illustrates the complex interplay that each model has with the host microenvironment. Conclusions: This study provides strategies to aid selection of xenograft models for therapeutic studies. These data highlight the dynamic nature of xenograft models and emphasize the importance of maintaining passage consistency throughout experiments. C1 [Hollingshead, Melinda G.] NCI, Biol Testing Branch, Frederick, MD 21702 USA. [Stockwin, Luke H.; Newton, Dianne L.; Bonomi, Carrie A.; Borgel, Suzanne D.; Divelbiss, Raymond; Dougherty, Kelly M.; Kimmel, David J.; Millione, Angelena; Mullendore, Michael E.; Stotler, Howard] Leidos Biomed Res Inc, Biol Testing Branch, Dev Therapeut Program, Frederick Natl Lab Canc Res, Frederick, MD 21702 USA. [Alcoser, Sergio Y.; Hager, Elizabeth J.] NCI, Biol Testing Branch, Dev Therapeut Program, Frederick, MD 21702 USA. [Orsburn, Benjamin C.] Thermo Fisher, Indianapolis, IN USA. [Holbeck, Susan L.; Kunkel, Mark W.] NCI, Informat Technol Branch, Dev Therapeut Program, Div Canc Treatment & Diag, Bethesda, MD 20892 USA. [Kaur, Gurmeet] NCI, Mol Pharmacol Branch, Dev Therapeut Program, Frederick, MD 21702 USA. [Collins, Jerry] NCI, Dev Therapeut Program, Div Canc Treatment & Diag, Bethesda, MD 20892 USA. RP Hollingshead, MG (reprint author), NCI, Biol Testing Branch, 1050 Boyles St,Bldg 1043,Room 11, Frederick, MD 21702 USA. EM hollingm@mail.nih.gov RI Alcoser, Sergio/G-9074-2012 OI Alcoser, Sergio/0000-0002-6896-2551 FU National Cancer Institute; National Institutes of Health [HHSN261200800001E]; Developmental Therapeutics Program in the Division of Cancer Treatment and Diagnosis of the National Cancer Institute 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. 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. NCI-Frederick is accredited by AAALAC International and follows the Public Health Service Policy for the Care and Use of Laboratory Animals. All animals used in this research project were cared for and used humanely according to the following policies: The U.S. Public Health Service Policy on Humane Care and Use of Animals (1996); the Guide for the Care and Use of Laboratory Animals Eighth Edition; and the U.S. Government Principles for Utilization and Care of Vertebrate Animals Used in Testing, Research, and Training (1985). All studies were approved by the NCI at Frederick Animal Care and Use Committee (ACUC) prior initiation of work. The NCI at Frederick ACUC operates under an active Office of Laboratory Animal Welfare assurance. NR 39 TC 4 Z9 4 U1 1 U2 9 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 MAY 22 PY 2014 VL 15 AR 393 DI 10.1186/1471-2164-15-393 PG 16 WC Biotechnology & Applied Microbiology; Genetics & Heredity SC Biotechnology & Applied Microbiology; Genetics & Heredity GA AI2IO UT WOS:000336681300001 PM 24885658 ER PT J AU Yang, H Volfovsky, N Rattray, A Chen, XF Tanaka, H Strathern, J AF Yang, Hui Volfovsky, Natalia Rattray, Alison Chen, Xiongfong Tanaka, Hisashi Strathern, Jeffrey TI GAP-Seq: a method for identification of DNA palindromes SO BMC GENOMICS LA English DT Article DE Palindrome; Gene amplification; Inversion-PCR; GAP-Seq; GAPF; Breakpoint; MCF7; Genome instability; Cancer; Human diseases ID CANCER CELL-LINES; COMPARATIVE GENOMIC HYBRIDIZATION; RECENT SEGMENTAL DUPLICATIONS; BREAST-CANCER; GENE AMPLIFICATION; INVERTED REPEATS; COPY NUMBER; REARRANGEMENTS; MECHANISMS; EVOLUTION AB Background: Closely spaced long inverted repeats, also known as DNA palindromes, can undergo intrastrand annealing to form DNA hairpins. The ability to form these hairpins results in genome instability, difficulties in maintaining clones in Escherichia coli and major problems for most DNA sequencing approaches. Because of their role in genomic instability and gene amplification in some human cancers, it is important to develop systematic approaches to detect and characterize DNA palindromes. Results: We developed a new protocol to identify palindromes that couples the S1 nuclease treated Cot0 DNA (GAPF) with high-throughput sequencing (GAP-Seq). Unlike earlier protocols, it does not involve restriction enzymatic digestion prior to DNA snap-back thereby preserving longer DNA sequences. It also indicates the location of the novel junction, which can then be recovered. Using MCF-7 breast cancer cell line as the proof-of-principle analysis, we have identified 35 palindrome candidates and physically characterized the top 5 candidates and their junctions. Because this protocol eliminates many of the false positives that plague earlier techniques, we have improved palindrome identification. Conclusions: The GAP-Seq approach underscores the importance of developing new tools for identifying and characterizing palindromes, and provides a new strategy to systematically assess palindromes in genomes. It will be useful for studying human cancers and other diseases associated with palindromes. C1 [Yang, Hui; Rattray, Alison; Strathern, Jeffrey] Canc Res & Dev Ctr, Frederick Natl Lab Canc Res, Gene Regulat & Chromosome Biol Lab, Frederick, MD 21702 USA. [Volfovsky, Natalia; Chen, Xiongfong] SAIC Frederick Inc, ISP ABCC7, Frederick Natl Lab Canc Res, Frederick, MD 21702 USA. [Tanaka, Hisashi] Cleveland Clin, Lerner Res Inst, Dept Mol Genet, Cleveland, OH 44195 USA. RP Strathern, J (reprint author), Canc Res & Dev Ctr, Frederick Natl Lab Canc Res, Gene Regulat & Chromosome Biol Lab, Frederick, MD 21702 USA. EM strathej@mail.nih.gov FU National Institutes of Health, National Cancer Institute, Center for Cancer Research, Frederick National Laboratory for Cancer Research [HHSN261200800001E, R01CA149385] FX The authors thank Dr. Adrian Lee for MCF-7 subline genomic DNA (MCF-7-neo, MCF-7-BK, MCF-7-B, MCF-7-C) and Dr. John Weinstein for MCF-7-NCI60 genomic DNA, Dr. Robert Stephens for helpful discussions, Dr. Duncan Donohue for providing the R-script for the prototype of the data visualization of Figure 4, Claudia Stewart for Roche 454 sequencing, Sandra Burkett for cell culture, Dr. Pieter Faber for Illumina sequencing, Dr. Thomas Schneider for discussion of mathematic equations and Dr. Sharon Moore for critique of the manuscript. This work was supported by the National Institutes of Health, National Cancer Institute, Center for Cancer Research, Frederick National Laboratory for Cancer Research (the Intramural Research Program, HHSN261200800001E to N.V. and X.C., R01CA149385 to H.T.). NR 48 TC 1 Z9 1 U1 1 U2 4 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 MAY 22 PY 2014 VL 15 AR 394 DI 10.1186/1471-2164-15-394 PG 12 WC Biotechnology & Applied Microbiology; Genetics & Heredity SC Biotechnology & Applied Microbiology; Genetics & Heredity GA AI5PP UT WOS:000336921800001 PM 24885769 ER PT J AU Mandl, JN Germain, RN AF Mandl, Judith N. Germain, Ronald N. TI Focusing in on T Cell Cross-Reactivity SO CELL LA English DT Editorial Material AB To provide broad immunity to a vast array of foreign antigens with a limited number of T lymphocytes, each cell has to recognize many targets. By implementing a strategy to identify T cell receptor (TCR) ligands and investigating at a fine granularity their structure and sequence relationship, Birnbaum et al. demonstrate the surprisingly tight focus of such T cell cross-reactivity. C1 [Mandl, Judith N.; Germain, Ronald N.] NIAID, Lymphocyte Biol Sect, Lab Syst Biol, NIH, Bethesda, MD 20892 USA. RP Mandl, JN (reprint author), NIAID, Lymphocyte Biol Sect, Lab Syst Biol, NIH, Bethesda, MD 20892 USA. EM mandlj@niaid.nih.gov; rgermain@niaid.nih.gov NR 5 TC 0 Z9 0 U1 0 U2 12 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 MAY 22 PY 2014 VL 157 IS 5 BP 1006 EP 1008 DI 10.1016/j.cell.2014.05.002 PG 4 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA AH9CG UT WOS:000336437200003 PM 24855938 ER PT J AU Warner, KD Homan, P Weeks, KM Smith, AG Abell, C Ferre-D'Amare, AR AF Warner, Katherine Deigan Homan, Philip Weeks, Kevin M. Smith, Alison G. Abell, Chris Ferre-D'Amare, Adrian R. TI Validating Fragment-Based Drug Discovery for Biological RNAs: Lead Fragments Bind and Remodel the TPP Riboswitch Specifically SO CHEMISTRY & BIOLOGY LA English DT Article ID THI-BOX RIBOSWITCH; GENE-REGULATION; CRYSTALLOGRAPHY; SOFTWARE; LIGAND AB Thiamine pyrophosphate (TPP) riboswitches regulate essential genes in bacteria by changing conformation upon binding intracellular TPP. Previous studies using fragment-based approaches identified small molecule "fragments" that bind this gene-regulatory mRNA domain. Crystallographic studies now show that, despite having micromolar K(d)s, four different fragments bind the TPP riboswitch site-specifically, occupying the pocket that recognizes the aminopyrimidine of TPP. Unexpectedly, the unoccupied site that would recognize the pyrophosphate of TPP rearranges into a structure distinct from that of the cognate complex. This idiosyncratic fragment-induced conformation, also characterized by small-angle X-ray scattering and chemical probing, represents a possible mechanism for adventitious ligand discrimination by the riboswitch, and suggests that off-pathway conformations of RNAs can be targeted for drug development. Our structures, together with previous screening studies, demonstrate the feasibility of fragment-based drug discovery against RNA targets. C1 [Warner, Katherine Deigan; Ferre-D'Amare, Adrian R.] NHLBI, Bethesda, MD 20892 USA. [Warner, Katherine Deigan; Abell, Chris] Univ Cambridge, Dept Chem, Cambridge CB2 1EW, England. [Homan, Philip; Weeks, Kevin M.] Univ N Carolina, Dept Chem, Chapel Hill, NC 27599 USA. [Smith, Alison G.] Univ Cambridge, Dept Plant Sci, Cambridge CB2 3EA, England. RP Ferre-D'Amare, AR (reprint author), NHLBI, 50 South Dr,MSC 8012, Bethesda, MD 20892 USA. EM adrian.ferre@nih.gov OI Smith, Alison/0000-0001-6511-5704 FU National Institute for General Medical Sciences, NIH; US Department of Energy; NIH [GM098662]; BBSRC of the UK; NIH-Oxford/Cambridge Research Scholars program; intramural program of the National Heart, Lung and Blood Institute, NIH FX We thank the staff at beamlines 24-ID-C of APS and 5.0.1 and 5.0.2 of ALS for crystallographic data collection support; N. Baird, Y.-X. Wang, and X. Fang for assistance with SAXS; G. Piszczek for assistance with ITC; and N. Baird, C. Jones, M. Lau, J. Posakony, S. Ryder, A. Serganov, M. Warner, and J. Zhang for discussions. This work is partly based on research conducted at ALS on the BCSB beamlines and at APS on the NE-CAT beamlines, all of which are supported by the National Institute for General Medical Sciences, NIH. Use of ALS and APS was supported by the US Department of Energy. This work was supported in part by the NIH (grant GM098662 to K. M. W.), the BBSRC of the UK, and the NIH-Oxford/Cambridge Research Scholars program. This work was supported in part by the intramural program of the National Heart, Lung and Blood Institute, NIH. NR 24 TC 20 Z9 20 U1 0 U2 15 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 1074-5521 EI 1879-1301 J9 CHEM BIOL JI Chem. Biol. PD MAY 22 PY 2014 VL 21 IS 5 BP 591 EP 595 DI 10.1016/j.chembiol.2014.03.007 PG 5 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA AH8XW UT WOS:000336422500008 PM 24768306 ER PT J AU Wang, HC Godage, HY Riley, AM Weaver, JD Shears, SB Potter, BVL AF Wang, Huanchen Godage, Himali Y. Riley, Andrew M. Weaver, Jeremy D. Shears, Stephen B. Potter, Barry V. L. TI Synthetic Inositol Phosphate Analogs Reveal that PPIP5K2 Has a Surface-Mounted Substrate Capture Site that Is a Target for Drug Discovery SO CHEMISTRY & BIOLOGY LA English DT Article ID DIPHOSPHOINOSITOL POLYPHOSPHATES; ANTHRANILATE PHOSPHORIBOSYLTRANSFERASE; TELOMERE LENGTH; PYROPHOSPHATES; MECHANISM; KINASE; DIPHOSPHATE; INHIBITION; PROVIDES; ENZYMES AB Diphosphoinositol pentakisphosphate kinase 2 (PPIP5K2) is one of the mammalian PPIP5K isoforms responsible for synthesis of diphosphoinositol polyphosphates (inositol pyrophosphates; PP-InsPs), regulatory molecules that function at the interface of cell signaling and organismic homeostasis. The development of drugs that inhibit PPIP5K2 could have both experimental and therapeutic applications. Here, we describe a synthetic strategy for producing naturally occurring 5-PP-InsP(4), as well as several inositol polyphosphate analogs, and we study their interactions with PPIP5K2 using biochemical and structural approaches. These experiments uncover an additional ligand-binding site on the surface of PPIP5K2, adjacent to the catalytic pocket. This site facilitates substrate capture from the bulk phase, prior to transfer into the catalytic pocket. In addition to demonstrating a "catch-and-pass" reaction mechanism in a small molecule kinase, we demonstrate that binding of our analogs to the substrate capture site inhibits PPIP5K2. This work suggests that the substrate-binding site offers new opportunities for targeted drug design. C1 [Wang, Huanchen; Weaver, Jeremy D.; Shears, Stephen B.] NIEHS, Inositol Signaling Grp, Lab Signal Transduct, NIH, Res Triangle Pk, NC 27709 USA. [Godage, Himali Y.; Riley, Andrew M.; Potter, Barry V. L.] Univ Bath, Dept Pharm & Pharmacol, Wolfson Lab Med Chem, Bath BA2 7AY, Avon, England. RP Shears, SB (reprint author), NIEHS, Inositol Signaling Grp, Lab Signal Transduct, NIH, POB 12233, Res Triangle Pk, NC 27709 USA. EM shears@niehs.nih.gov; b.v.l.potter@bath.ac.uk RI Riley, Andrew/F-3526-2013 FU Wellcome Trust [082837, 101010]; Intramural Research Program of the NIH/National Institute of Environmental Health Sciences (NIEHS); US Department of Energy, Office of Science, Office of Basic Energy Sciences [W-31-109-Eng-38] FX We thank the Wellcome Trust (program grant 082837 to A.M.R. and B.V.L.P.) for support. B.V.L.P. is a Wellcome Trust Senior Investigator (grant 101010). This research was also supported by the Intramural Research Program of the NIH/National Institute of Environmental Health Sciences (NIEHS). X-ray data were collected at Southeast Regional Collaborative Access Team (SERCAT) 22-beamline at the Advanced Photon Source (APS), Argonne National Laboratory. Supporting institutions may be found at http://www.ser-cat.org/members.html. Use of the APS was supported by the US Department of Energy, Office of Science, Office of Basic Energy Sciences, under contract no. W-31-109-Eng-38. We also thank the NIEHS collaborative crystallography group for assistance with data collection. NR 29 TC 11 Z9 11 U1 4 U2 14 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 1074-5521 EI 1879-1301 J9 CHEM BIOL JI Chem. Biol. PD MAY 22 PY 2014 VL 21 IS 5 BP 689 EP 699 DI 10.1016/j.chembiol.2014.03.009 PG 11 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA AH8XW UT WOS:000336422500018 PM 24768307 ER PT J AU Arighi, CN Wu, CH Cohen, KB Hirschman, L Krallinger, M Valencia, A Lu, ZY Wilbur, JW Wiegers, TC AF Arighi, Cecilia N. Wu, Cathy H. Cohen, Kevin B. Hirschman, Lynette Krallinger, Martin Valencia, Alfonso Lu, Zhiyong Wilbur, John W. Wiegers, Thomas C. TI BioCreative-IV virtual issue SO DATABASE-THE JOURNAL OF BIOLOGICAL DATABASES AND CURATION LA English DT Editorial Material ID GENE NORMALIZATION; INFORMATION; ONTOGENE; BIOLOGY; II.5; TEXT; PIE C1 [Arighi, Cecilia N.; Wu, Cathy H.] Univ Delaware, Ctr Bioinformat & Computat Biol, Newark, DE 19716 USA. [Cohen, Kevin B.] Univ Colorado Denver, Sch Med, Ctr Computat Pharmacol, Aurora, CO USA. [Hirschman, Lynette] Mitre Corp, Bedford, MA 01730 USA. [Krallinger, Martin; Valencia, Alfonso] Spanish Natl Canc Res Ctr, Struct & Computat Biol Grp, Madrid, Spain. [Lu, Zhiyong; Wilbur, John W.] Natl Lib Med, Natl Ctr Biotechnol Informat, Bethesda, MD 20894 USA. [Wiegers, Thomas C.] N Carolina State Univ, Dept Biol Sci, Raleigh, NC 27695 USA. RP Arighi, CN (reprint author), Univ Delaware, Ctr Bioinformat & Computat Biol, Newark, DE 19716 USA. EM arighi@dbi.udel.edu RI Valencia, Alfonso/I-3127-2015; OI Valencia, Alfonso/0000-0002-8937-6789; Arighi, Cecilia/0000-0002-0803-4817 NR 35 TC 10 Z9 10 U1 0 U2 3 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 1758-0463 J9 DATABASE-OXFORD JI Database PD MAY 22 PY 2014 AR bau039 DI 10.1093/database/bau039 PG 6 WC Mathematical & Computational Biology SC Mathematical & Computational Biology GA AH6RB UT WOS:000336257300001 ER PT J AU Rai, G Joshi, N Jung, JE Liu, Y Schultz, L Yasgar, A Perry, S Diaz, G Zhang, QL Kenyon, V Jadhav, A Simeonov, A Lo, EH van Leyen, K Maloney, DJ Holman, TR AF Rai, Ganesha Joshi, Netra Jung, Joo Eun Liu, Yu Schultz, Lena Yasgar, Adam Perry, Steve Diaz, Giovanni Zhang, Qiangli Kenyon, Victor Jadhav, Ajit Simeonov, Anton Lo, Eng H. van Leyen, Klaus Maloney, David J. Holman, Theodore R. TI Potent and Selective Inhibitors of Human Reticulocyte 12/15-Lipoxygenase as Anti-Stroke Therapies SO JOURNAL OF MEDICINAL CHEMISTRY LA English DT Article ID PLATELET-TYPE 12-LIPOXYGENASE; SPONGE-DERIVED TERPENOIDS; TRANSIENT FOCAL ISCHEMIA; PANCREATIC-CANCER CELLS; OXIDATIVE STRESS; HUMAN 15-LIPOXYGENASE; 5-LIPOXYGENASE INHIBITION; MAMMALIAN 15-LIPOXYGENASE; GLUTATHIONE DEPLETION; RHEUMATOID-ARTHRITIS AB A key challenge facing drug discovery today is variability of the drug target between species, such as with 12/15-lipoxygenase (12/15-LOX), which contributes to ischemic brain injury, but its human and rodent isozymes have different inhibitor specificities. In the current work, we have utilized a quantitative high-throughput (qHTS) screen to identify compound 1 (ML351), a novel chemotype for 12/15-LOX inhibition that has nanomolar potency (IC50 = 200 nM) against human 12/15-LOX and is protective against oxidative glutamate toxicity in mouse neuronal HT22 cells. In addition, it exhibited greater than 250-fold selectivity versus related LOX isozymes, was a mixed inhibitor, and did not reduce the active-site ferric ion. Lastly, 1 significantly reduced infarct size following permanent focal ischemia in a mouse model of ischemic stroke. As such, this represents the first report of a selective inhibitor of human 12/15-LOX with demonstrated in vivo activity in proof-of-concept mouse models of stroke. C1 [Jung, Joo Eun; Liu, Yu; Lo, Eng H.; van Leyen, Klaus] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Neuroprotect Res Lab,Dept Radiol, Charlestown, MA 02129 USA. [Rai, Ganesha; Schultz, Lena; Yasgar, Adam; Jadhav, Ajit; Simeonov, Anton; Maloney, David J.] NIH, Natl Ctr Adv Translat Sci, Bethesda, MD 20892 USA. [Joshi, Netra; Perry, Steve; Diaz, Giovanni; Zhang, Qiangli; Kenyon, Victor; Holman, Theodore R.] Univ Calif Santa Cruz, Dept Chem & Biochem, Santa Cruz, CA 95064 USA. RP van Leyen, K (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Neuroprotect Res Lab,Dept Radiol, Charlestown, MA 02129 USA. EM klaus_vanleyen@hms.harvard.edu; maloneyd@mail.nih.gov; tholman@chemistry.ucsc.edu FU National Institute of Health [R01 GM56062, R01 NS049430, R01 NS069939]; Molecular Libraries Initiative of the National Institutes of Health Roadmap for Medical Research [R03 MH081283, U54MH084681]; National Center for Advancing Translational Sciences; NIH [S10-RR20939]; California Institute for Quantitative Biosciences FX We thank Sam Michael and Richard Jones for automation support; Paul Shinn and Danielle van Leer for assistance with compound management; William Leister, Heather Baker, James Bougie, Elizabeth Fernandez, and Christopher Leclair for analytical chemistry and purification support; Kimloan Nguyen for in vitro ADME data; and Eric Hoobler for helping with the COX assays. Financial support was from the National Institute of Health (grants R01 GM56062 (T.R.H.), R01 NS049430 (K.v.L.), and R01 NS069939) and the Molecular Libraries Initiative of the National Institutes of Health Roadmap for Medical Research (R03 MH081283 (T.R.H.)). G.R., L.S., A.Y., A.J., A.S., and D.J.M. were supported by the intramural research program of the National Center for Advancing Translational Sciences and the Molecular Libraries Initiative of the National Institutes of Health Roadmap for Medical Research (U54MH084681). Additional financial support was from NIH (S10-RR20939 (T.R.H.)) and the California Institute for Quantitative Biosciences for the UCSC MS Facility (T.R.H.). NR 79 TC 21 Z9 21 U1 4 U2 13 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 MAY 22 PY 2014 VL 57 IS 10 BP 4035 EP 4048 DI 10.1021/jm401915r PG 14 WC Chemistry, Medicinal SC Pharmacology & Pharmacy GA AI0BB UT WOS:000336510100010 PM 24684213 ER PT J AU Singh, S Prasad, NR Chufan, EE Patel, BA Wang, YJ Chen, ZS Ambudkar, SV Talele, TT AF Singh, Satyakam Prasad, Nagarajan Rajendra Chufan, Eduardo E. Patel, Bhargav A. Wang, Yi-Jun Chen, Zhe-Sheng Ambudkar, Suresh V. Talele, Tanaji T. TI Design and Synthesis of Human ABCB1 (P-Glycoprotein) Inhibitors by Peptide Coupling of Diverse Chemical Scaffolds on Carboxyl and Amino Termini of (S)-Valine-Derived Thiazole Amino Acid SO JOURNAL OF MEDICINAL CHEMISTRY LA English DT Article ID ATP-DEPENDENT TRANSPORTERS; RESISTANCE REVERSAL AGENTS; MULTIDRUG-RESISTANCE; DRUG TRANSPORTERS; POTENT MODULATOR; MAMMALIAN-CELLS; IN-VIVO; BINDING; CANCER; PHARMACOPHORE AB P-glycoprotein (P-gp) serves as a therapeutic target for the development of multidrug resistance reversal agents. In this study, we synthesized 21 novel compounds by peptide coupling at corresponding carboxyl and amino termini of (S)-valine-based bis-thiazole and monothiazole derivatives with diverse chemical scaffolds. Using calcein-AM efflux assay, we identified compound 28 (IC50 = 1.0 mu M) carrying 3,4,5-trimethoxybenzoyl and 2-aminobenzophenone groups, respectively, at the amino and carboxyl termini of the monothiazole zwitter-ion. Compound 28 inhibited the photolabeling of P-gp with [I-125]-iodoarylazidoprazosin with IC50 = 0.75 mu M and stimulated the basal ATP hydrolysis of P-gp in a concentration-dependent manner (EC50 ATPase = 0.027 mu M). Compound 28 at 3 mu M reduced resistance in cytotoxicity assay to paclitaxel in P-gp-expressing SW620/Ad300 and HEK/ABCB1 cell lines. Biochemical and docking studies showed site-1 to be the preferable binding site for 28 within the drug-binding pocket of human P-gp. C1 [Singh, Satyakam; Patel, Bhargav A.; Wang, Yi-Jun; Chen, Zhe-Sheng; Talele, Tanaji T.] St Johns Univ, Coll Pharm & Hlth Sci, Dept Pharmaceut Sci, Queens, NY 11439 USA. [Prasad, Nagarajan Rajendra; Chufan, Eduardo E.; Ambudkar, Suresh V.] NCI, Cell Biol Lab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. RP Ambudkar, SV (reprint author), NCI, Cell Biol Lab, Ctr Canc Res, NIH, Bldg 37, Bethesda, MD 20892 USA. EM ambudkar@mail.nih.gov; talelet@stjohns.edu RI Wang, Yi-Jun/K-3218-2016 FU Department of Pharmaceutical Sciences of St. John's University; St. John's University [579-1110]; NIH, National Cancer Institute, Center for Cancer Research; Indian Council of Medical Research, New Delhi [Indo/FRC/452(Y-19)/2012-13IHD] FX This research was supported by the Department of Pharmaceutical Sciences of St. John's University and St. John's University Seed Grant no. 579-1110 to T.T.T. Drs. N.R.P., E.E.C., and S.V.A. were supported by the Intramural Research Program of the NIH, National Cancer Institute, Center for Cancer Research. Financial support from Indian Council of Medical Research, New Delhi, in the form of International Fellowship for Young Indian Biomedical Scientists to Dr. N.R.P. is gratefully acknowledged (Indo/FRC/452(Y-19)/2012-13IHD). We acknowledge Drs. Susan E. Bates and Robert W. Robey (NCI, NIH, Bethesda, MD) for providing SW620 and SW620/Ad300 cell lines. We thank Dr. Stephen Aller (The University of Alabama at Birmingham, Birmingham, AL) for generously providing human apo-state P-gp homology model. We thank George Leiman for editorial assistance. S.S. and T.T.T. are thankful to Dr. Sanjai Kumar and Dibyendu Dana (Queens College-CUNY, Queens, NY) for assisting in ESI-MS and HRMS analyses. NR 37 TC 13 Z9 13 U1 1 U2 12 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 MAY 22 PY 2014 VL 57 IS 10 BP 4058 EP 4072 DI 10.1021/jm401966m PG 15 WC Chemistry, Medicinal SC Pharmacology & Pharmacy GA AI0BB UT WOS:000336510100012 PM 24773054 ER PT J AU Lv, PC Agama, K Marchand, C Pommier, Y Cushman, M AF Lv, Peng-Cheng Agama, Keli Marchand, Christophe Pommier, Yves Cushman, Mark TI Design, Synthesis, and Biological Evaluation of O-2-Modified Indenoisoquinolines as Dual Topoisomerase I-Tyrosyl-DNA Phosphodiesterase I Inhibitors SO JOURNAL OF MEDICINAL CHEMISTRY LA English DT Article ID POTENTIAL ANTICANCER AGENTS; PHOSPHOLIPASE-D SUPERFAMILY; CLEAVAGE COMPLEXES; CAMPTOTHECIN RESISTANCE; CATALYTIC MECHANISM; COVALENT COMPLEXES; ANTITUMOR-ACTIVITY; CRYSTAL-STRUCTURE; STRAND BREAKS; CELL-LINE AB Tyrosyl-DNA phosphodiesterase I (TDP1) repairs stalled topoisomerase I (Topl) DNA covalent complexes and has been proposed to be a promising and attractive target for cancer treatment. Inhibitors of TDPI could conceivably act synergistically with Topl inhibitors and thereby potentiate the effects of Top! poisons. This study describes the successful design and synthesis of 2-position-modified indenoisoquinolines as dual Topl TDPI inhibitors using a structure-based drug design approach. Enzyme inhibition studies indicate that indenoisoquinolines modified at the 2-position with three-carbon side chains ending with amino substituents show both promising Top! and TDP1 inhibitory activity. Molecular modeling of selected target compounds bound to Topl and TDPI was used to rationalize the enzyme inhibition results and structure activity relationship analysis. C1 [Lv, Peng-Cheng; Cushman, Mark] Purdue Univ, Dept Med Chem & Mol Pharmacol, Coll Pharm, W Lafayette, IN 47907 USA. [Lv, Peng-Cheng; Cushman, Mark] Purdue Univ, Purdue Ctr Canc Res, W Lafayette, IN 47907 USA. [Agama, Keli; Marchand, Christophe; Pommier, Yves] NCI, Dev Therapeut Branch, Ctr Canc Res, Bethesda, MD 20892 USA. [Agama, Keli; Marchand, Christophe; Pommier, Yves] NCI, Mol Pharmacol Lab, Ctr Canc Res, Bethesda, MD 20892 USA. RP Cushman, M (reprint author), Purdue Univ, Dept Med Chem & Mol Pharmacol, Coll Pharm, W Lafayette, IN 47907 USA. EM cushman@purdue.edu FU National Institutes of Health (NIH) [UO1 CA89566]; Intramural Research Program, Center for Cancer Research, National Cancer Institute, NIH [Z01 BC 006161, Z01 BC 006150]; Developmental Therapeutics Program at the National Cancer Institute [NO1-CO-56000] FX This work was made possible by the National Institutes of Health (NIH) through support from research grant UO1 CA89566 and was supported by the Intramural Research Program, Center for Cancer Research, National Cancer Institute, NIH (Z01 BC 006161 and Z01 BC 006150). In vitro cytotoxicity testing was performed by the Developmental Therapeutics Program at the National Cancer Institute under contract NO1-CO-56000. NR 71 TC 13 Z9 14 U1 1 U2 29 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 MAY 22 PY 2014 VL 57 IS 10 BP 4324 EP 4336 DI 10.1021/jm500294a PG 13 WC Chemistry, Medicinal SC Pharmacology & Pharmacy GA AI0BB UT WOS:000336510100030 PM 24800942 ER PT J AU Liang, TJ Ghany, MG AF Liang, T. Jake Ghany, Marc G. TI Therapy of Hepatitis C - Back to the Future SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Editorial Material ID VIRUS-INFECTION; SOFOSBUVIR; BOCEPREVIR C1 [Liang, T. Jake; Ghany, Marc G.] NIDDK, NIH, Bethesda, MD 20892 USA. RP Liang, TJ (reprint author), NIDDK, NIH, Bethesda, MD 20892 USA. NR 19 TC 47 Z9 47 U1 0 U2 7 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 MAY 22 PY 2014 VL 370 IS 21 BP 2043 EP 2047 DI 10.1056/NEJMe1403619 PG 5 WC Medicine, General & Internal SC General & Internal Medicine GA AH4UZ UT WOS:000336125500013 PM 24795199 ER PT J AU Martinez-Bakker, M Bakker, KM King, AA Rohani, P AF Martinez-Bakker, Micaela Bakker, Kevin M. King, Aaron A. Rohani, Pejman TI Human birth seasonality: latitudinal gradient and interplay with childhood disease dynamics SO PROCEEDINGS OF THE ROYAL SOCIETY B-BIOLOGICAL SCIENCES LA English DT Article DE birth; seasonality; measles; disease; latitude ID HUMAN-REPRODUCTION; RECURRENT EPIDEMICS; INFECTIOUS-DISEASES; HOUSE FINCHES; UNITED-STATES; MEASLES; TRANSMISSION; VACCINATION; PATTERNS; RATES AB More than a century of ecological studies have demonstrated the importance of demography in shaping spatial and temporal variation in population dynamics. Surprisingly, the impact of seasonal recruitment on infectious disease systems has received much less attention. Here, we present data encompassing 78 years of monthly natality in the USA, and reveal pronounced seasonality in birth rates, with geographical and temporal variation in both the peak birth timing and amplitude. The timing of annual birth pulses followed a latitudinal gradient, with northern states exhibiting spring/summer peaks and southern states exhibiting autumn peaks, a pattern we also observed throughout the Northern Hemisphere. Additionally, the amplitude of United States birth seasonality was more than twofold greater in southern states versus those in the north. Next, we examined the dynamical impact of birth seasonality on childhood disease incidence, using a mechanistic model of measles. Birth seasonality was found to have the potential to alter the magnitude and periodicity of epidemics, with the effect dependent on both birth peak timing and amplitude. In a simulation study, we fitted an susceptible-exposed-infected-recovered model to simulated data, and demonstrated that ignoring birth seasonality can bias the estimation of critical epidemiological parameters. Finally, we carried out statistical inference using historical measles incidence data from New York City. Our analyses did not identify the predicted systematic biases in parameter estimates. This may be owing to the well-known frequency-locking between measles epidemics and seasonal transmission rates, or may arise from substantial uncertainty in multiple model parameters and estimation stochasticity. C1 [Martinez-Bakker, Micaela; Bakker, Kevin M.; King, Aaron A.; Rohani, Pejman] Univ Michigan, Dept Ecol & Evolutionary Biol, Ann Arbor, MI 48109 USA. [Martinez-Bakker, Micaela; Bakker, Kevin M.; King, Aaron A.; Rohani, Pejman] Univ Michigan, Ctr Study Complex Syst, Ann Arbor, MI 48109 USA. [King, Aaron A.] Univ Michigan, Dept Math, Ann Arbor, MI 48109 USA. [King, Aaron A.; Rohani, Pejman] NIH, Fogarty Int Ctr, Bethesda, MD 20892 USA. RP Martinez-Bakker, M (reprint author), Univ Michigan, Dept Ecol & Evolutionary Biol, Ann Arbor, MI 48109 USA. EM bakkerma@umich.edu RI Martinez-Bakker, Micaela/J-3721-2013 OI Martinez-Bakker, Micaela/0000-0002-9248-9450 FU NSF; Research and Policy in Infectious Disease Dynamics programme of the Science and Technology Directorate, Department of Homeland Security; Fogarty International Center, National Institutes of Health; National Institutes of Health [R01AI101155] FX M.M.B. is supported by the NSF Graduate Research Fellowship Programme. P.R. and A.A.K. are supported by the Research and Policy in Infectious Disease Dynamics programme of the Science and Technology Directorate, Department of Homeland Security, the Fogarty International Center, National Institutes of Health and by a research grant from the National Institutes of Health (R01AI101155). NR 59 TC 13 Z9 13 U1 3 U2 25 PU ROYAL SOC PI LONDON PA 6-9 CARLTON HOUSE TERRACE, LONDON SW1Y 5AG, ENGLAND SN 0962-8452 EI 1471-2954 J9 P ROY SOC B-BIOL SCI JI Proc. R. Soc. B-Biol. Sci. PD MAY 22 PY 2014 VL 281 IS 1783 AR 20132438 DI 10.1098/rspb.2013.2438 PG 8 WC Biology; Ecology; Evolutionary Biology SC Life Sciences & Biomedicine - Other Topics; Environmental Sciences & Ecology; Evolutionary Biology GA AF0NP UT WOS:000334411600001 PM 24695423 ER PT J AU Orecchioni, M Bedognetti, D Sgarrella, F Marincola, FM Bianco, A Delogu, LG AF Orecchioni, Marco Bedognetti, Davide Sgarrella, Francesco Marincola, Francesco M. Bianco, Alberto Delogu, Lucia Gemma TI Impact of carbon nanotubes and graphene on immune cells SO JOURNAL OF TRANSLATIONAL MEDICINE LA English DT Review DE Carbon nanotubes; Graphene; Graphene oxide; Nanomedicine; Immune system; Cells; Therapy; Diagnosis ID NLRP3 INFLAMMASOME ACTIVATION; ASBESTOS-LIKE PATHOGENICITY; IN-VITRO; RAW 264.7; SIGNALING PATHWAYS; PULMONARY TOXICITY; CONTRAST AGENTS; CELLULAR ACTIVATION; PRISTINE GRAPHENE; PHAGOCYTIC-CELLS AB It has been recently proposed that nanomaterials, alone or in concert with their specific biomolecular conjugates, can be used to directly modulate the immune system, therefore offering a new tool for the enhancement of immune-based therapies against infectious disease and cancer. Here, we revised the publications on the impact of functionalized carbon nanotubes (f-CNTs), graphene and carbon nanohorns on immune cells. Whereas f-CNTs are the nanomaterial most widely investigated, we noticed a progressive increase of studies focusing on graphene in the last couple of years. The majority of the works (56%) have been carried out on macrophages, following by lymphocytes (30% of the studies). In the case of lymphocytes, T cells were the most investigated (22%) followed by monocytes and dendritic cells (7%), mixed cell populations (peripheral blood mononuclear cells, 6%), and B and natural killer (NK) cells (1%). Most of the studies focused on toxicity and biocompatibility, while mechanistic insights on the effect of carbon nanotubes on immune cells are generally lacking. Only very recently high-throughput gene-expression analyses have shed new lights on unrecognized effects of carbon nanomaterials on the immune system. These investigations have demonstrated that some f-CNTs can directly elicitate specific inflammatory pathways. The interaction of graphene with the immune system is still at a very early stage of investigation. This comprehensive state of the art on biocompatible f-CNTs and graphene on immune cells provides a useful compass to guide future researches on immunological applications of carbon nanomaterials in medicine. C1 [Orecchioni, Marco; Sgarrella, Francesco; Delogu, Lucia Gemma] Univ Sassari, Dipartimento Chim & Farm, I-07100 Sassari, Italy. [Bedognetti, Davide; Marincola, Francesco M.] NIH, Infect Dis & Immunogenet Sect, Dept Transfus Med, Ctr Clin, Bethesda, MD 20892 USA. [Bedognetti, Davide; Marincola, Francesco M.] NIH, Trans Natl Inst Hlth Ctr Human Immunol, Bethesda, MD 20892 USA. [Bedognetti, Davide; Marincola, Francesco M.] Sidra Med & Res Ctr, Res Branch, Doha, Qatar. [Bianco, Alberto] CNRS, Inst Biol Mol & Cellulaire, Lab Immunopathol & Chim Therapeut, F-67000 Strasbourg, France. RP Bianco, A (reprint author), CNRS, Inst Biol Mol & Cellulaire, Lab Immunopathol & Chim Therapeut, F-67000 Strasbourg, France. EM a.bianco@ibmc-cnrs.unistra.fr; lgdelogu@uniss.it OI Bedognetti, Davide/0000-0002-5857-773X FU Fondazione Banco di Sardegna [186/2011.0484, 2013.1308]; Sardinia Region [CRP-59720]; Intramural Research program of the U. S. National Institutes of Health (Department of Transfusion Medicine, Clinical Center); Gianfranco Del Prete The future: medicine, biology and nanotechnology Award FX This work was partly supported by the Fondazione Banco di Sardegna (grant No 186/2011.0484, 2013.1308 To L. G. D.), the Sardinia Region (grant No CRP-59720 to L. G. D.). This work was supported in part by the Intramural Research program of the U. S. National Institutes of Health (Department of Transfusion Medicine, Clinical Center) and "Gianfranco Del Prete The future: medicine, biology and nanotechnology Award" to L. G. D. A. B. wishes to thank the CNRS. L. G. D. wishes to thank the Sardinian Region for an invited professorship to A. NR 114 TC 29 Z9 29 U1 8 U2 91 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 MAY 21 PY 2014 VL 12 AR 138 DI 10.1186/1479-5876-12-138 PG 11 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA AK5MQ UT WOS:000338469300003 PM 24885781 ER PT J AU Barnes, SJ Cheetham, CEJ AF Barnes, Samuel J. Cheetham, Claire E. J. TI A Role for Short-Lived Synapses in Adult Cortex? SO JOURNAL OF NEUROSCIENCE LA English DT Editorial Material ID IN-VIVO; SPINE STABILITY; NEOCORTEX; GROWTH C1 [Barnes, Samuel J.] Kings Coll London, MRC, Ctr Dev Neurobiol, London SE1 1UL, England. [Cheetham, Claire E. J.] NINDS, Bethesda, MD 20892 USA. RP Cheetham, CEJ (reprint author), NINDS, 35 Convent Dr, Bethesda, MD 20892 USA. EM claire.cheetham@nih.gov RI Barnes, Samuel/I-5805-2015; Cheetham, Claire/A-2612-2017 OI Cheetham, Claire/0000-0002-4038-1501 NR 11 TC 1 Z9 1 U1 1 U2 5 PU SOC NEUROSCIENCE PI WASHINGTON PA 11 DUPONT CIRCLE, NW, STE 500, WASHINGTON, DC 20036 USA SN 0270-6474 J9 J NEUROSCI JI J. Neurosci. PD MAY 21 PY 2014 VL 34 IS 21 BP 7044 EP 7046 DI 10.1523/JNEUROSCI.1108-14.2014 PG 3 WC Neurosciences SC Neurosciences & Neurology GA AI5HB UT WOS:000336895200002 PM 24849340 ER PT J AU Zavala, BA Tan, HL Little, S Ashkan, K Hariz, M Foltynie, T Zrinzo, L Zaghloul, KA Brown, P AF Zavala, Baltazar A. Tan, Huiling Little, Simon Ashkan, Keyoumars Hariz, Marwan Foltynie, Thomas Zrinzo, Ludvic Zaghloul, Kareem A. Brown, Peter TI Midline Frontal Cortex Low-Frequency Activity Drives Subthalamic Nucleus Oscillations during Conflict SO JOURNAL OF NEUROSCIENCE LA English DT Article DE conflict; midline frontal cortex; subthalamic nucleus; theta oscillations ID ANTERIOR CINGULATE CORTEX; DEEP BRAIN-STIMULATION; INCREASES RESPONSE-TIME; PARKINSONS-DISEASE; BASAL GANGLIA; DECISION-MAKING; TASK-DIFFICULTY; IMPULSE CONTROL; THETA ENERGY; EEG-DATA AB Making the right decision from conflicting information takes time. Recent computational, electrophysiological, and clinical studies have implicated two brain areas as being crucial in assuring sufficient time is taken for decision-making under conditions of conflict: the medial prefrontal cortex and the subthalamic nucleus (STN). Both structures exhibit an elevation of activity at low frequencies (<10 Hz) during conflict that correlates with the amount of time taken to respond. This suggests that the two sites could become functionally coupled during conflict. To establish the nature of this interaction we recorded from deep-brain stimulation electrodes implanted bilaterally in the STN of 13 Parkinson's disease patients while they performed a sensory integration task involving randomly moving dots. By gradually increasing the number of dots moving coherently in one direction, we were able to determine changes in the STN associated with response execution. Furthermore, by occasionally having 10% of the dots move in the opposite direction as the majority, we were able to identify an independent increase in STN theta-delta activity triggered by conflict. Crucially, simultaneous midline frontal electroencephalographic recordings revealed an increase in the theta-delta band coherence between the two structures that was specific to high-conflict trials. Activity over the midline frontal cortex was Granger causal to that in STN. These results establish the cortico-subcortical circuit enabling successful choices to be made under conditions of conflict and provide support for the hypothesis that the brain uses frequency-specific channels of communication to convey behaviorally relevant information. C1 [Zavala, Baltazar A.; Tan, Huiling; Little, Simon; Brown, Peter] Univ Oxford, Nuffield Dept Clin Neurol, John Radcliffe Hosp, Expt Neurol Grp, Oxford OX3 9DU, England. [Zavala, Baltazar A.; Zaghloul, Kareem A.] NIH, Surg Neurol Branch, Bethesda, MD 20814 USA. [Ashkan, Keyoumars] Kings Coll London, Dept Neurosurg, Kings Coll Hosp, London SE5 9RS, England. [Hariz, Marwan; Foltynie, Thomas; Zrinzo, Ludvic] UCL, Inst Neurol, Sobell Dept Motor Neurosci & Movement Disorders, London WC1 3BG, England. RP Brown, P (reprint author), Univ Oxford, Nuffield Dept Clin Neurol, John Radcliffe Hosp, Level 6,West Wing, Oxford OX3 9DU, England. EM peter.brown@ndcn.ox.ac.uk RI Brown, Peter/J-4307-2016; OI Brown, Peter/0000-0002-5201-3044; Tan, Huiling /0000-0001-8038-3029 FU Rhodes Trust; National Institutes of Health Oxford-Cambridge fellowship; Department of Health National Institute for Health Research UCL Biomedical Research Center; Monument Trust; Parkinson's Appeal for Deep Brain Stimulation; Medical Research Council; Department of Health National Institute for Health Research Oxford Biomedical Research Centre; Wellcome Trust FX B.Z. is supported by the Rhodes Trust and the National Institutes of Health Oxford-Cambridge fellowship. M.H., T. F., and L.Z. are funded by the Department of Health National Institute for Health Research UCL Biomedical Research Center, The Monument Trust, and Parkinson's Appeal for Deep Brain Stimulation. P. B. and H. T. are funded by the Medical Research Council, and P. B. further funded by the Department of Health National Institute for Health Research Oxford Biomedical Research Centre. S. L. is funded by the Wellcome Trust. This work was partly carried out in the NIHR cognitive health Clinical Research Facility, Oxford. We thank Mr Alex Green and Prof Aziz for letting us enlist the help of case 1. NR 60 TC 27 Z9 27 U1 5 U2 18 PU SOC NEUROSCIENCE PI WASHINGTON PA 11 DUPONT CIRCLE, NW, STE 500, WASHINGTON, DC 20036 USA SN 0270-6474 J9 J NEUROSCI JI J. Neurosci. PD MAY 21 PY 2014 VL 34 IS 21 BP 7322 EP 7333 DI 10.1523/JNEUROSCI.1169-14.2014 PG 12 WC Neurosciences SC Neurosciences & Neurology GA AI5HB UT WOS:000336895200026 PM 24849364 ER PT J AU de Renty, C DePamphilis, ML Ullah, Z AF de Renty, Christelle DePamphilis, Melvin L. Ullah, Zakir TI Cytoplasmic Localization of p21 Protects Trophoblast Giant Cells from DNA Damage Induced Apoptosis SO PLOS ONE LA English DT Article ID STEM-CELLS; CDK INHIBITORS; MICE LACKING; CYCLE EXIT; DOWN-REGULATION; MOUSE EMBRYOS; DIFFERENTIATION; KINASE; PHOSPHORYLATION; PROLIFERATION AB Proliferating trophoblast stem cells (TSCs) can differentiate into nonproliferating but viable trophoblast giant cells (TGCs) that are resistant to DNA damage induced apoptosis. Differentiation is associated with selective up-regulation of the Cip/Kip cyclin-dependent kinase inhibitors p57 and p21; expression of p27 remains constant. Previous studies showed that p57 localizes to the nucleus in TGCs where it is essential for endoreplication. Here we show that p27 also remains localized to the nucleus during TSC differentiation where it complements the role of p57. Unexpectedly, p21 localized to the cytoplasm where it was maintained throughout both the G-and S-phases of endocycles, and where it prevented DNA damage induced apoptosis. This unusual status for a Cip/Kip protein was dependent on site-specific phosphorylation of p21 by the Akt1 kinase that is also up-regulated in TGCs. Although cytoplasmic p21 is widespread among cancer cells, among normal cells it has been observed only in monocytes. The fact that it also occurs in TGCs reveals that p57 and p21 serve nonredundant functions, and suggests that the role of p21 in suppressing apoptosis is restricted to terminally differentiated cells. C1 [de Renty, Christelle; DePamphilis, Melvin L.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, NIH, Bethesda, MD USA. [Ullah, Zakir] Lahore Univ Management Sci, Sch Sci & Engn, Dept Biol, Lahore, Pakistan. RP Ullah, Z (reprint author), Lahore Univ Management Sci, Sch Sci & Engn, Dept Biol, Lahore, Pakistan. EM zakirullah@lums.edu.pk FU NICHD; LUMS University FX This work was supported by the NICHD intramural research program and by LUMS University. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 72 TC 4 Z9 4 U1 0 U2 3 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA SN 1932-6203 J9 PLOS ONE JI PLoS One PD MAY 21 PY 2014 VL 9 IS 5 AR e97434 DI 10.1371/journal.pone.0097434 PG 15 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA AI3AL UT WOS:000336730600028 PM 24848107 ER PT J AU Malik, N Wang, XT Shah, S Efthymiou, AG Yan, B Heman-Ackah, S Zhan, M Rao, M AF Malik, Nasir Wang, Xiantao Shah, Sonia Efthymiou, Anastasia G. Yan, Bin Heman-Ackah, Sabrina Zhan, Ming Rao, Mahendra TI Comparison of the Gene Expression Profiles of Human Fetal Cortical Astrocytes with Pluripotent Stem Cell Derived Neural Stem Cells Identifies Human Astrocyte Markers and Signaling Pathways and Transcription Factors Active in Human Astrocytes SO PLOS ONE LA English DT Article ID DEVELOPING SPINAL-CORD; CENTRAL-NERVOUS-SYSTEM; PRECURSOR CELLS; MOUSE-BRAIN; NEURONS; GLIOGENESIS; EFFICIENT; PROTEIN; DIFFERENTIATION; DISEASE AB Astrocytes are the most abundant cell type in the central nervous system (CNS) and have a multitude of functions that include maintenance of CNS homeostasis, trophic support of neurons, detoxification, and immune surveillance. It has only recently been appreciated that astrocyte dysfunction is a primary cause of many neurological disorders. Despite their importance in disease very little is known about global gene expression for human astrocytes. We have performed a microarray expression analysis of human fetal astrocytes to identify genes and signaling pathways that are important for astrocyte development and maintenance. Our analysis confirmed that the fetal astrocytes express high levels of the core astrocyte marker GFAP and the transcription factors from the NFI family which have been shown to play important roles in astrocyte development. A group of novel markers were identified that distinguish fetal astrocytes from pluripotent stem cell-derived neural stem cells (NSCs) and NSC-derived neurons. As in murine astrocytes, the Notch signaling pathway appears to be particularly important for cell fate decisions between the astrocyte and neuronal lineages in human astrocytes. These findings unveil the repertoire of genes expressed in human astrocytes and serve as a basis for further studies to better understand astrocyte biology, especially as it relates to disease. C1 [Malik, Nasir; Wang, Xiantao; Shah, Sonia; Efthymiou, Anastasia G.; Heman-Ackah, Sabrina; Rao, Mahendra] NIAMS, NIH, Bethesda, MD 20892 USA. [Yan, Bin] Hong Kong Baptist Univ, Dept Biol, Hong Kong, Hong Kong, Peoples R China. [Zhan, Ming] Weill Cornell Med Coll, Methodist Hosp Res Inst, Houston, TX USA. [Rao, Mahendra] NIH Ctr Regenerat Med, NIH, Bethesda, MD USA. RP Malik, N (reprint author), NIAMS, NIH, Bethesda, MD 20892 USA. EM malikn@mail.nih.gov OI Efthymiou, Anastasia/0000-0002-1769-5078 FU National Institutes of Health (NIH) Common Fund FX This research was supported by the National Institutes of Health (NIH) Common Fund. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 50 TC 11 Z9 11 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 MAY 21 PY 2014 VL 9 IS 5 AR e96139 DI 10.1371/journal.pone.0096139 PG 16 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA AI3AL UT WOS:000336730600009 PM 24848099 ER PT J AU Sugiyama, N Murayama, A Suzuki, R Watanabe, N Shiina, M Liang, TJ Wakita, T Kato, T AF Sugiyama, Nao Murayama, Asako Suzuki, Ryosuke Watanabe, Noriyuki Shiina, Masaaki Liang, T. Jake Wakita, Takaji Kato, Takanobu TI Single Strain Isolation Method for Cell Culture-Adapted Hepatitis C Virus by End-Point Dilution and Infection SO PLOS ONE LA English DT Article ID TRANS-ENCAPSIDATION; PROTEIN; MUTATIONS; PARTICLES; SYSTEM; IDENTIFICATION; REPLICATION; CHIMPANZEES; ADAPTATION; GENOME AB The hepatitis C virus (HCV) culture system has enabled us to clarify the HCV life cycle and essential host factors for propagation. However, the virus production level of wild-type JFH-1 (JFH-1/wt) is limited, and this leads to difficulties in performing experiments that require higher viral concentrations. As the cell culture-adapted JFH-1 has been reported to have robust virus production, some mutations in the viral genome may play a role in the efficiency of virus production. In this study, we obtained cell culture-adapted virus by passage of full-length JFH-1 RNA-transfected Huh-7.5.1 cells. The obtained virus produced 3 log-fold more progeny viruses as compared with JFH-1/wt. Several mutations were identified as being responsible for robust virus production, but, on reverse-genetics analysis, the production levels of JFH-1 with these mutations did not reach the level of cell culture-adapted virus. By using the single strain isolation method by end-point dilution and infection, we isolated two strains with additional mutations, and found that these strains have the ability to produce more progeny viruses. On reverse-genetics analysis, the strains with these additional mutations were able to produce robust progeny viruses at comparable levels as cell culture-adapted JFH-1 virus. The strategy used in this study will be useful for identifying strains with unique characteristics, such as robust virus production, from a diverse population, and for determining the responsible mutations for these characteristics. C1 [Sugiyama, Nao; Murayama, Asako; Suzuki, Ryosuke; Watanabe, Noriyuki; Wakita, Takaji; Kato, Takanobu] Natl Inst Infect Dis, Dept Virol 2, Tokyo, Japan. [Shiina, Masaaki] Shin Yurigaoka Gen Hosp, Dept Gastroenterol & Hepatol, Kawasaki, Kanagawa, Japan. [Liang, T. Jake] NIDDK, Liver Dis Branch, NIH, Bethesda, MD 20892 USA. RP Kato, T (reprint author), Natl Inst Infect Dis, Dept Virol 2, Tokyo, Japan. EM takato@nih.go.jp FU Japan Society for the Promotion of Science; Ministry of Health, Labour and Welfare of Japan; Ministry of Education, Culture, Sports, Science and Technology of Japan FX This work was supported in part by Grants-in-Aid for Scientific Research from the Japan Society for the Promotion of Science, from the Ministry of Health, Labour and Welfare of Japan, and from the Ministry of Education, Culture, Sports, Science and Technology of Japan. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 38 TC 3 Z9 3 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 MAY 21 PY 2014 VL 9 IS 5 AR e98168 DI 10.1371/journal.pone.0098168 PG 8 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA AI3AL UT WOS:000336730600094 PM 24848954 ER PT J AU Xiang, Y Eyers, F Young, IG Rosenberg, HF Foster, PS Yang, M AF Xiang, Yang Eyers, Fiona Young, Ian G. Rosenberg, Helene F. Foster, Paul S. Yang, Ming TI Identification of MicroRNAs Regulating the Developmental Pathways of Bone Marrow Derived Mast Cells SO PLOS ONE LA English DT Article ID C-KIT LIGAND; IMMUNE-RESPONSES; EXPRESSION; MURINE; DISEASE; MASTOCYTOSIS; ACTIVATION; LINEAGES; DECREASE; SURVIVAL AB Background: MicroRNAs (miRNAs) play important roles in leukocyte differentiation, although those utilised for specific programs and key functions remain incompletely characterised. As a global approach to gain insights into the potential regulatory role of miRNA in mast cell differentiation we characterised expression in BM cultures from the initiation of differentiation. In cultures enriched in differentiating mast cells we characterised miRNA expression and identified miRNA targeting the mRNA of putative factors involved in differentiation pathways and cellular identity. Detailed pathway analysis identified a unique miRNA network that is intimately linked to the mast cell differentiation program. Methodology/Principal Findings: We identified 86 unique miRNAs with expression patterns that were up-or downregulated at 5-fold or more during bone marrow derived mast cells (BMMC) development. By employing TargetScan and MeSH databases, we identified 524 transcripts involved in 30 canonical pathways as potentially regulated by these specific 86 miRNAs. Furthermore, by applying miRanda and IPA analyses, we predict that 7 specific miRNAs of this group are directly associated with the expression of c-Kit and Fc epsilon RI alpha and likewise, that 18 miRNAs promote expression of Mitf, GATA1 and c/EBP alpha three core transcription factors that direct mast cell differentiation. Furthermore, we have identified 11 miRNAs that may regulate the expression of STATs-3, -5a/b, GATA2 and GATA3 during differentiation, along with 13 miRNAs that target transcripts encoding Ndst2, mMCP4 and mMCP6 and thus may regulate biosynthesis of mast cell secretory mediators. Conclusions/Significance: This investigation characterises changes in miRNA expression in whole BM cultures during the differentiation of mast cells and predicts functional links between miRNAs and their target mRNAs for the regulation of development. This information provides an important resource for further investigations of the contributions of miRNAs to mast cell differentiation and function. C1 [Xiang, Yang; Eyers, Fiona; Foster, Paul S.; Yang, Ming] Univ Newcastle, Fac Hlth, Sch Biomed Sci & Pharm, Ctr Asthma & Resp Dis, Callaghan, NSW 2308, Australia. [Xiang, Yang; Eyers, Fiona; Foster, Paul S.; Yang, Ming] Hunter Med Res Inst, Callaghan, NSW, Australia. [Xiang, Yang] Cent S Univ, Xiangya Sch Med, Dept Physiol, Changsha, Hunan, Peoples R China. [Young, Ian G.] Australian Natl Univ, John Curtin Sch Med Res, Dept Mol Biosci, Canberra, ACT 2601, Australia. [Rosenberg, Helene F.] NIAID, Inflammat Immunobiol Sect, Lab Allerg Dis, NIH, Bethesda, MD 20892 USA. RP Foster, PS (reprint author), Univ Newcastle, Fac Hlth, Sch Biomed Sci & Pharm, Ctr Asthma & Resp Dis, Callaghan, NSW 2308, Australia. EM Paul.Foster@newcastle.edu.au; Ming.Yang@newcastle.edu.au FU National Health and Medical Research Council of Australia; Australian Research Council; Cooperative Research Centre for Asthma and Airways; National Institute of Allergy and Infectious Diseases Division of Intramural Research FX The authors are supported by the National Health and Medical Research Council of Australia, the Australian Research Council, the Cooperative Research Centre for Asthma and Airways and National Institute of Allergy and Infectious Diseases Division of Intramural Research. The funding bodies had no further role in study design; in the collection, analysis and interpretation of data; in the writing of the report; or in the decision to submit the paper for publication. NR 47 TC 9 Z9 10 U1 0 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 MAY 21 PY 2014 VL 9 IS 5 AR e98139 DI 10.1371/journal.pone.0098139 PG 13 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA AI3AL UT WOS:000336730600091 PM 24848502 ER PT J AU Highfill, SL Cui, YZ Giles, AJ Smith, JP Zhang, H Morse, E Kaplan, RN Mackall, CL AF Highfill, Steven L. Cui, Yongzhi Giles, Amber J. Smith, Jillian P. Zhang, Hua Morse, Elizabeth Kaplan, Rosandra N. Mackall, Crystal L. TI Disruption of CXCR2-Mediated MDSC Tumor Trafficking Enhances Anti-PD1 Efficacy SO SCIENCE TRANSLATIONAL MEDICINE LA English DT Article ID RENAL-CELL CARCINOMA; SUPPRESSOR-CELLS; MYELOID CELLS; CANCER; EXPRESSION; RECEPTOR; INTERLEUKIN-8; IMMUNOTHERAPY; PD-1; RHABDOMYOSARCOMA AB Suppression of the host's immune system plays a major role in cancer progression. Tumor signaling of programmed death 1 (PD1) on T cells and expansion of myeloid-derived suppressor cells (MDSCs) are major mechanisms of tumor immune escape. We sought to target these pathways in rhabdomyosarcoma (RMS), the most common soft tissue sarcoma of childhood. Murine RMS showed high surface expression of PD-L1, and anti-PD1 prevented tumor growth if initiated early after tumor inoculation; however, delayed anti-PD1 had limited benefit. RMS induced robust expansion of CXCR2(+)CD11b(+)Ly6G(hi) MDSCs, and CXCR2 deficiency prevented CD11b(+)Ly6G(hi) MDSC trafficking to the tumor. When tumor trafficking of MDSCs was inhibited by CXCR2 deficiency, or after anti-CXCR2 monoclonal antibody therapy, delayed anti-PD1 treatment induced significant antitumor effects. Thus, CXCR2+ CD11b(+) Ly6G(hi) MDSCs mediate local immunosuppression, which limits the efficacy of checkpoint blockade in murine RMS. Human pediatric sarcomas also produce CXCR2 ligands, including CXCL8. Patients with metastatic pediatric sarcomas display elevated serum CXCR2 ligands, and elevated CXCL8 is associated with diminished survival in this population. We conclude that accumulation of MDSCs in the tumor bed limits the efficacy of checkpoint blockade in cancer. We also identify CXCR2 as a novel target for modulating tumor immune escape and present evidence that CXCR2+ CD11b+ Ly6Ghi MDSCs are an important suppressive myeloid subset in pediatric sarcomas. These findings present a translatable strategy to improve the efficacy of checkpoint blockade by preventing trafficking of MDSCs to the tumor site. C1 [Highfill, Steven L.; Cui, Yongzhi; Giles, Amber J.; Smith, Jillian P.; Zhang, Hua; Morse, Elizabeth; Kaplan, Rosandra N.; Mackall, Crystal L.] NCI, Pediat Oncol Branch, NIH, Bethesda, MD 20892 USA. RP Mackall, CL (reprint author), NCI, Pediat Oncol Branch, NIH, Bethesda, MD 20892 USA. EM cm35c@nih.gov FU NIH Intramural Research Program; Liddy Shriver Sarcoma Initiative FX This work was supported in part by the NIH Intramural Research Program as well as by funding from the Liddy Shriver Sarcoma Initiative. NR 48 TC 54 Z9 57 U1 1 U2 20 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 MAY 21 PY 2014 VL 6 IS 237 AR 237ra67 DI 10.1126/scitranslmed.3007974 PG 13 WC Cell Biology; Medicine, Research & Experimental SC Cell Biology; Research & Experimental Medicine GA AI2DY UT WOS:000336668800007 PM 24848257 ER PT J AU Schmidt, TM Alam, NM Chen, S Kofuji, P Li, W Prusky, GT Hattar, S AF Schmidt, Tiffany M. Alam, Nazia M. Chen, Shan Kofuji, Paulo Li, Wei Prusky, Glen T. Hattar, Samer TI A Role for Melanopsin in Alpha Retinal Ganglion Cells and Contrast Detection SO NEURON LA English DT Article ID CAT RETINA; SPATIAL VISION; MOUSE; SYSTEM; PROJECTIONS; ADAPTATION; IRRADIANCE; NEURONS; RATS; MICE AB Distinct subclasses of retinal ganglion cells (RGCs) mediate vision and nonimage-forming functions such as circadian photoentrainment. This distinction stems from studies that ablated melanopsin-expressing intrinsically photosensitive RGCs (ipRGCs) and showed deficits in nonimage-forming behaviors, but not image vision. However, we show that the ON alpha RGC, a conventional RGC type, is intrinsically photosensitive in mammals. In addition to their classical response to fast changes in contrast through rod/cone signaling, melanopsin expression allows ON alpha RGCs to signal prior light exposure and environmental luminance over long periods of time. Consistent with the high contrast sensitivity of ON alpha RGCs, mice lacking either melanopsin or ON alpha RGCs have behavioral deficits in contrast sensitivity. These findings indicate a surprising role for melanopsin and ipRGCs in vision. C1 [Schmidt, Tiffany M.; Hattar, Samer] Johns Hopkins Univ, Dept Biol, Baltimore, MD 21218 USA. [Alam, Nazia M.; Prusky, Glen T.] Weill Cornell Med Coll, Burke Med Res Inst, Dept Physiol & Biophys, White Plains, NY 10605 USA. [Chen, Shan; Li, Wei] NEI, NIH, Bethesda, MD 20892 USA. [Kofuji, Paulo] Univ Minnesota, Dept Neurosci, Minneapolis, MN 55455 USA. [Hattar, Samer] Johns Hopkins Univ, Dept Neurosci, Baltimore, MD 21218 USA. RP Schmidt, TM (reprint author), Johns Hopkins Univ, Dept Biol, Baltimore, MD 21218 USA. EM tmschmidt@jhu.edu RI Schmidt, Tiffany/A-9660-2012; Schmidt, Tiffany /L-7598-2014; OI Schmidt, Tiffany/0000-0002-4791-6775; Schmidt, Tiffany /0000-0002-4791-6775; Kofuji, Paulo/0000-0002-4840-9986 FU National Institutes of Health [GM076430, EY022543]; NIH; Burke Foundation FX We would like to thank Drs. Marnie Halpern, Rejji Kuruvilla, Haiqing Zhao, Robert F. Miller, and Stewart Hendry for comments on the manuscript. We would also like to thank Dr. Cara Altimus, Ms. Diane Vig, and Mr. Nathan Schmidt for technical assistance. This work was funded by National Institutes of Health grants GM076430 (S. H.) and EY022543 (T. M. S.), the NIH Intramural Research Program (W. L.), and the Burke Foundation (G. T. P.). G. T. P. is a principal at Cerebral Mechanics, which manufactures equipment and software used in this study. NR 33 TC 41 Z9 41 U1 4 U2 20 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 MAY 21 PY 2014 VL 82 IS 4 BP 781 EP 788 DI 10.1016/j.neuron.2014.03.022 PG 8 WC Neurosciences SC Neurosciences & Neurology GA AH8IA UT WOS:000336379800009 PM 24853938 ER PT J AU Jinsmaa, Y Sullivan, P Gross, D Cooney, A Sharabi, Y Goldstein, DS AF Jinsmaa, Yunden Sullivan, Patricia Gross, Daniel Cooney, Adele Sharabi, Yehonatan Goldstein, David S. TI Divalent metal ions enhance DOPAL-induced oligomerization of alpha-synuclein SO NEUROSCIENCE LETTERS LA English DT Article DE Alpha-synuclein; Oligomerization; Dopamine; Copper; DOPAL; Parkinson disease ID TOXIC DOPAMINE METABOLITE; PARKINSONS-DISEASE; LEWY BODIES; 3,4-DIHYDROXYPHENYLACETALDEHYDE; AGGREGATION; COPPER; IRON; OXIDATION; FERRITIN; BINDING AB Parkinson disease (PD) features profound striatal dopamine depletion and Lewy bodies containing abundant precipitated alpha-synuclein. Mechanisms linking alpha-synucleinopathy with the death of dopamine neurons remain incompletely understood. One such link may be 3,4-dihydroxyphenylacetaldehyde (DOPAL). All of the intra-neuronal metabolism of dopamine passes through DOPAL, which is toxic. DOPAL also potently oligomerizes alpha-synuclein and alpha-synuclein oligomers are thought to be pathogenic in PD. Another implicated factor in PD pathogenesis is metal ions, and alpha-synuclein contains binding sites for these ions. In this study we tested whether divalent metal ions augment DOPAL-induced oligomerization of alpha-synuclein in cell-free system and in PC12 cells conditionally over-expressing alpha-synuclein. Incubation with divalent metal ions augmented DOPAL-induced oligomerization of alpha-synuclein (Cu2+ > Fe2+ > Mn2+), whereas monovalent Cu1+ and trivalent Fe3+ were without effect. Other dopamine metabolites, dopamine itself, and metal ions alone or in combination with dopamine, also had no effect. Antioxidant treatment with ascorbic acid and divalent cation chelation with EDTA attenuated the augmentation by Cu2+ of DOPAL-induced alpha-synuclein oligomerization. Incubation of PC12 cells with L-DOPA markedly increased intracellular DOPAL content and promoted alpha-synuclein dimerization. Co-incubation with Cu2+ amplified (p = 0.01), while monoamine oxidase inhibition prevented, L-DOPA-related dimerization of alpha-synuclein (p = 0.01). We conclude that divalent metal ions augment DOPAL-induced oligomerization of alpha-synuclein. Drugs that interfere with this interaction might constitute a novel approach for future treatment or prevention approaches. (C) 2014 Elsevier Ireland Ltd. All rights reserved. C1 [Jinsmaa, Yunden; Sullivan, Patricia; Gross, Daniel; Cooney, Adele; Sharabi, Yehonatan; Goldstein, David S.] NINDS, Clin Neurocardiol Sect, NIH, Bethesda, MD 20892 USA. RP Goldstein, DS (reprint author), NINDS, Clin Neurocardiol Sect, NIH, 10 Ctr Dr MSC-1620,Bldg 10,5N220, Bethesda, MD 20892 USA. EM goldsteind@ninds.nih.gov FU NINDS FX We thank Dr. Kenneth L. Kirk for providing the DOPAL used in our experiments. The research was supported by the intramural research program of the NINDS. NR 21 TC 16 Z9 16 U1 0 U2 8 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0304-3940 EI 1872-7972 J9 NEUROSCI LETT JI Neurosci. Lett. PD MAY 21 PY 2014 VL 569 BP 27 EP 32 DI 10.1016/j.neulet.2014.03.016 PG 6 WC Neurosciences SC Neurosciences & Neurology GA AH8AI UT WOS:000336356100006 PM 24670480 ER PT J AU Kris, MG Johnson, BE Berry, LD Kwiatkowski, DJ Iafrate, AJ Wistuba, II Varella-Garcia, M Franklin, WA Aronson, SL Su, PF Shyr, Y Camidge, DR Sequist, LV Glisson, BS Khuri, FR Garon, EB Pao, W Rudin, C Schiller, J Haura, EB Socinski, M Shirai, K Chen, HD Giaccone, G Ladanyi, M Kugler, K Minna, JD Bunn, PA AF Kris, Mark G. Johnson, Bruce E. Berry, Lynne D. Kwiatkowski, David J. Iafrate, A. John Wistuba, Ignacio I. Varella-Garcia, Marileila Franklin, Wilbur A. Aronson, Samuel L. Su, Pei-Fang Shyr, Yu Camidge, D. Ross Sequist, Lecia V. Glisson, Bonnie S. Khuri, Fadlo R. Garon, Edward B. Pao, William Rudin, Charles Schiller, Joan Haura, Eric B. Socinski, Mark Shirai, Keisuke Chen, Heidi Giaccone, Giuseppe Ladanyi, Marc Kugler, Kelly Minna, John D. Bunn, Paul A. TI Using Multiplexed Assays of Oncogenic Drivers in Lung Cancers to Select Targeted Drugs SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Article ID PROTEIN EXPRESSION; MUTATIONS; ADENOCARCINOMA; GENE; EGFR; GEFITINIB; THERAPY; IDENTIFICATION; MULTICENTER; SENSITIVITY AB IMPORTANCE Targeting oncogenic drivers (genomic alterations critical to cancer development and maintenance) has transformed the care of patients with lung adenocarcinomas. The Lung Cancer Mutation Consortium was formed to perform multiplexed assays testing adenocarcinomas of the lung for drivers in 10 genes to enable clinicians to select targeted treatments and enroll patients into clinical trials. OBJECTIVES To determine the frequency of oncogenic drivers in patients with lung adenocarcinomas and to use the data to select treatments targeting the identified driver(s) and measure survival. DESIGN, SETTING, AND PARTICIPANTS From 2009 through 2012, 14 sites in the United States enrolled patients with metastatic lung adenocarcinomas and a performance status of 0 through 2 and tested their tumors for 10 drivers. Information was collected on patients, therapies, and survival. INTERVENTIONS Tumors were tested for 10 oncogenic drivers, and results were used to select matched targeted therapies. MAIN OUTCOMES AND MEASURES Determination of the frequency of oncogenic drivers, the proportion of patients treated with genotype-directed therapy, and survival. RESULTS From 2009 through 2012, tumors from 1007 patients were tested for at least 1 gene and 733 for 10 genes (patients with full genotyping). An oncogenic driver was found in 466 of 733 patients (64%). Among these 733 tumors, 182 tumors (25%) had the KRAS driver; sensitizing EGFR, 122 (17%); ALK rearrangements, 57 (8%); other EGFR, 29 (4%); 2 or more genes, 24 (3%); ERBB2 (formerly HER2), 19 (3%); BRAF, 16 (2%); PIK3CA, 6 (<1%); MET amplification, 5 (<1%); NRAS, 5 (<1%); MEK1, 1 (<1%); AKT1, 0. Results were used to select a targeted therapy or trial in 275 of 1007 patients (28%). The median survival was 3.5 years (interquartile range [IQR], 1.96-7.70) for the 260 patients with an oncogenic driver and genotype-directed therapy compared with 2.4 years (IQR, 0.88-6.20) for the 318 patients with any oncogenic driver(s) who did not receive genotype-directed therapy (propensity score-adjusted hazard ratio, 0.69 [95% CI, 0.53-0.9], P = .006). CONCLUSIONS AND RELEVANCE Actionable drivers were detected in 64% of lung adenocarcinomas. Multiplexed testing aided physicians in selecting therapies. Although individuals with drivers receiving a matched targeted agent lived longer, randomized trials are required to determine if targeting therapy based on oncogenic drivers improves survival. C1 [Kris, Mark G.; Ladanyi, Marc] Mem Sloan Kettering Canc Ctr, New York, NY 10065 USA. [Johnson, Bruce E.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Berry, Lynne D.; Su, Pei-Fang; Shyr, Yu; Pao, William; Chen, Heidi] Vanderbilt Ingram Canc Ctr, Nashville, TN USA. [Kwiatkowski, David J.] Brigham & Womens Hosp, Boston, MA 02115 USA. [Iafrate, A. John; Sequist, Lecia V.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Wistuba, Ignacio I.; Glisson, Bonnie S.] Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA. [Varella-Garcia, Marileila; Franklin, Wilbur A.; Camidge, D. Ross; Kugler, Kelly; Bunn, Paul A.] Univ Colorado, Canc Ctr Denver, Aurora, CO USA. [Aronson, Samuel L.] Partners HealthCare Ctr Personalized Genet Med, Boston, MA USA. [Khuri, Fadlo R.] Emory Univ, Winship Canc Inst, Atlanta, GA 30322 USA. [Garon, Edward B.] Univ Calif Los Angeles, David Geffen Sch Med, Los Angeles, CA 90095 USA. [Rudin, Charles] Johns Hopkins Univ, Sidney Kimmel Comprehens Canc Ctr, Baltimore, MD USA. [Schiller, Joan; Minna, John D.] Univ Texas Southwestern, Med Ctr, Dallas, TX USA. [Haura, Eric B.] Univ S Florida, Coll Med, H Lee Moffitt Canc Ctr & Res Inst, Tampa, FL 33612 USA. [Socinski, Mark] Univ Pittsburgh, Inst Canc, Pittsburgh, PA USA. [Shirai, Keisuke] Med Univ S Carolina, Charleston, SC USA. [Giaccone, Giuseppe] NCI, Bethesda, MD 20892 USA. [Giaccone, Giuseppe] Georgetown Univ, Sch Med, Washington, DC USA. RP Kris, MG (reprint author), Mem Sloan Kettering Canc Ctr, 300 E 66th St, New York, NY 10065 USA. EM krism@mskcc.org RI Giaccone, Giuseppe/E-8297-2017; OI Giaccone, Giuseppe/0000-0002-5023-7562; Kris, Mark/0000-0002-7317-5341 FU National Institutes of Health, National Cancer Institute [HSS NIH NCI 1RC2CA148394-010] FX This study was entirely supported by a grant from the National Institutes of Health, National Cancer Institute (HSS NIH NCI 1RC2CA148394-010). NR 41 TC 305 Z9 326 U1 5 U2 37 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 MAY 21 PY 2014 VL 311 IS 19 BP 1998 EP 2006 DI 10.1001/jama.2014.3741 PG 9 WC Medicine, General & Internal SC General & Internal Medicine GA AH4UA UT WOS:000336122800022 PM 24846037 ER PT J AU Buxbaum, JD Bolshakova, N Brownfeld, JM Anney, RJL Bender, P Bernier, R Cook, EH Coon, H Cuccaro, M Freitag, CM Hallmayer, J Geschwind, D Klauck, SM Nurnberger, JI Oliveira, G Pinto, D Poustka, F Scherer, SW Shih, A Sutcliffe, JS Szatmari, P Vicente, AM Vieland, V Gallagher, L AF Buxbaum, Joseph D. Bolshakova, Nadia Brownfeld, Jessica M. Anney, Richard J. L. Bender, Patrick Bernier, Raphael Cook, Edwin H. Coon, Hilary Cuccaro, Michael Freitag, Christine M. Hallmayer, Joachim Geschwind, Daniel Klauck, Sabine M. Nurnberger, John I. Oliveira, Guiomar Pinto, Dalila Poustka, Fritz Scherer, Stephen W. Shih, Andy Sutcliffe, James S. Szatmari, Peter Vicente, Astrid M. Vieland, Veronica Gallagher, Louise TI The Autism Simplex Collection: an international, expertly phenotyped autism sample for genetic and phenotypic analyses SO MOLECULAR AUTISM LA English DT Article ID DE-NOVO MUTATIONS; COPY NUMBER VARIATION; SPECTRUM DISORDERS; COMMUNICATION CHECKLIST; GENOME; INDIVIDUALS; SCALE; RISK; IDENTIFICATION; VALIDATION AB Background: There is an urgent need for expanding and enhancing autism spectrum disorder (ASD) samples, in order to better understand causes of ASD. Methods: In a unique public-private partnership, 13 sites with extensive experience in both the assessment and diagnosis of ASD embarked on an ambitious, 2-year programto collect samples for genetic and phenotypic research and begin analyses on these samples. The program was called The Autism Simplex Collection (TASC). TASC sample collection began in 2008 and was completed in 2010, and included nine sites from North America and four sites from Western Europe, as well as a centralized Data Coordinating Center. Results: Over 1,700 trios are part of this collection, with DNA from transformed cells now available through the National Institute of Mental Health (NIMH). Autism Diagnostic Interview-Revised (ADI-R) and Autism Diagnostic Observation Schedule-Generic (ADOS-G) measures are available for all probands, as are standardized IQ measures, Vineland Adaptive Behavioral Scales (VABS), the Social Responsiveness Scale (SRS), Peabody Picture Vocabulary Test (PPVT), and physical measures (height, weight, and head circumference). At almost every site, additional phenotypic measures were collected, including the Broad Autism Phenotype Questionnaire (BAPQ) and Repetitive Behavior Scale-Revised (RBS-R), as well as the non-word repetition scale, Communication Checklist (Children's or Adult), and Aberrant Behavior Checklist (ABC). Moreover, for nearly 1,000 trios, the Autism Genome Project Consortium (AGP) has carried out Illumina 1 M SNP genotyping and called copy number variation (CNV) in the samples, with data being made available through the National Institutes of Health (NIH). Whole exome sequencing (WES) has been carried out in over 500 probands, together with ancestry matched controls, and this data is also available through the NIH. Additional WES is being carried out by the Autism Sequencing Consortium (ASC), where the focus is on sequencing complete trios. ASC sequencing for the first 1,000 samples (all from whole-blood DNA) is complete and data will be released in 2014. Data is being made available through NIH databases (database of Genotypes and Phenotypes (dbGaP) and National Database for Autism Research (NDAR)) with DNA released in Dist 11.0. Primary funding for the collection, genotyping, sequencing and distribution of TASC samples was provided by Autism Speaks and the NIH, including the National Institute of Mental Health (NIMH) and the National Human Genetics Research Institute (NHGRI). Conclusions: TASC represents an important sample set that leverages expert sites. Similar approaches, leveraging expert sites and ongoing studies, represent an important path towards further enhancing available ASD samples. C1 [Buxbaum, Joseph D.; Brownfeld, Jessica M.; Pinto, Dalila] Icahn Sch Med Mt Sinai, Seaver Autism Ctr Res & Treatment, Dept Psychiat, New York, NY 10029 USA. [Bolshakova, Nadia; Anney, Richard J. L.; Gallagher, Louise] Autism Genet Grp, Sch Med, Dept Psychiat, Trin Coll, Dublin 8, Ireland. [Bender, Patrick] NIMH, Bethesda, MD 20892 USA. [Bernier, Raphael] Univ Washington, Dept Psychiat & Behav Sci, Seattle, WA 98195 USA. [Cook, Edwin H.] Univ Illinois, Inst Juvenile Res, Dept Psychiat, Chicago, IL 60608 USA. [Coon, Hilary] Univ Utah, Dept Psychiat, Sch Med, Salt Lake City, UT 84108 USA. [Cuccaro, Michael] Univ Miami, John P Hussman Inst Human Genom, Miami, FL 33101 USA. [Freitag, Christine M.; Poustka, Fritz] JW Goethe Univ Frankfurt, Dept Child & Adolescent Psychiat Psychosomat & Ps, D-60528 Frankfurt, Germany. [Hallmayer, Joachim] Stanford Sch Med, Dept Psychiat & Behav Sci Child & Adolescent Psyc, Stanford, CA USA. [Geschwind, Daniel] Univ Calif Los Angeles, Dept Neurol, Sch Med, Los Angeles, CA 90095 USA. [Klauck, Sabine M.] German Canc Res Ctr, D-69120 Heidelberg, Germany. [Nurnberger, John I.] Indiana Univ, Dept Psychiat, Sch Med, Indianapolis, IN 46202 USA. [Oliveira, Guiomar] Ctr Hosp, Unidade Neurodesenvolvimento & Autismo, Serv Ctr Desenvolvimento Crianca, P-3000602 Coimbra, Portugal. [Oliveira, Guiomar] Ctr Hosp, Ctr Invest & Form Clin, Pediat Hosp, P-3000602 Coimbra, Portugal. [Oliveira, Guiomar] Univ Coimbra, P-3000602 Coimbra, Portugal. [Oliveira, Guiomar] Univ Clin Pediat, P-3000602 Coimbra, Portugal. [Oliveira, Guiomar] Univ Coimbra, Inst Biomed Imaging & Life Sci, Fac Med, P-3000602 Coimbra, Portugal. [Scherer, Stephen W.] Hosp Sick Children, Ctr Appl Genom, Dept Mol Genet, Toronto, ON M5G 1X8, Canada. [Scherer, Stephen W.] McLaughlin Ctr, Toronto, ON M5G 1X8, Canada. [Scherer, Stephen W.] Univ Toronto, Toronto, ON M5G 1X8, Canada. [Shih, Andy] Autism Speaks, New York, NY 10016 USA. [Sutcliffe, James S.] Vanderbilt Univ, Dept Mol Physiol & Biophys, Vanderbilt Kennedy Ctr, Nashville, TN 37232 USA. [Sutcliffe, James S.] Vanderbilt Univ, Ctr Human Genet Res & Mol Neurosci, Nashville, TN 37232 USA. [Szatmari, Peter] McMaster Univ, Dept Psychiat & Behav Neurosci, Hamilton, ON L8N 3Z5, Canada. [Vicente, Astrid M.] Inst Nacl Saude Dr Ricardo Jorge, P-1649016 Lisbon, Portugal. [Vicente, Astrid M.] Inst Gulbenkian Ciencias, P-2781901 Oeiras, Portugal. [Vicente, Astrid M.] BioFIG Ctr Biodivers Funct & Integrat Genom, P-1749016 Lisbon, Portugal. [Vieland, Veronica] Ohio State Univ, Res Inst, Nationwide Childrens Hosp, Columbus, OH 43210 USA. RP Buxbaum, JD (reprint author), Icahn Sch Med Mt Sinai, Seaver Autism Ctr Res & Treatment, Dept Psychiat, New York, NY 10029 USA. EM joseph.buxbaum@mssm.edu; lgallagh@tcd.ie RI Scherer, Stephen /B-3785-2013; Sutcliffe, James/C-1348-2012; OI Scherer, Stephen /0000-0002-8326-1999; Sutcliffe, James/0000-0001-5200-6007; Coon, Hilary/0000-0002-8877-5446; Gallagher, Louise/0000-0001-9462-2836; Nurnberger, John/0000-0002-7674-1767; Buxbaum, Joseph/0000-0001-8898-8313; Anney, Richard/0000-0002-6083-407X; Oliveira, Guiomar/0000-0002-7049-1277 FU National Institutes of Health [MH094303, MH100233] FX The TASC consortium collection and genotyping was supported by Autism Speaks. Funding for the sequencing and distribution of TASC samples was provided by the National Institutes of Health (MH094303 and MH100233). We thank Dr. Bernie Devlin for thoughtful comments on the manuscript. NR 43 TC 9 Z9 9 U1 4 U2 14 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 2040-2392 J9 MOL AUTISM JI Mol. Autism PD MAY 20 PY 2014 VL 5 AR 34 DI 10.1186/2040-2392-5-34 PG 8 WC Genetics & Heredity; Neurosciences SC Genetics & Heredity; Neurosciences & Neurology GA CC6BL UT WOS:000350449400001 PM 25392729 ER PT J AU Fliedner, SMJ Engel, T Lendvai, NK Shankavaram, U Nolting, S Wesley, R Elkahloun, AG Ungefroren, H Oldoerp, A Lampert, G Lehnert, H Timmers, H Pacak, K AF Fliedner, Stephanie M. J. Engel, Tobias Lendvai, Nikoletta K. Shankavaram, Uma Noelting, Svenja Wesley, Robert Elkahloun, Abdel G. Ungefroren, Hendrik Oldoerp, Angela Lampert, Gary Lehnert, Hendrik Timmers, Henri Pacak, Karel TI Anti-Cancer Potential of MAPK Pathway Inhibition in Paragangliomas-Effect of Different Statins on Mouse Pheochromocytoma Cells SO PLOS ONE LA English DT Article ID SIGNALING PATHWAYS; MEVALONATE PATHWAY; MELANOMA-CELLS; SPORADIC PHEOCHROMOCYTOMA; REDUCTASE INHIBITORS; GERMLINE MUTATIONS; RET PROTOONCOGENE; SOMATIC MUTATIONS; INDUCE APOPTOSIS; DOWN-REGULATION AB To date, malignant pheochromocytomas and paragangliomas (PHEOs/PGLs) cannot be effectively cured and thus novel treatment strategies are urgently needed. Lovastatin has been shown to effectively induce apoptosis in mouse PHEO cells (MPC) and the more aggressive mouse tumor tissue-derived cells (MTT), which was accompanied by decreased phosphorylation of mitogen-activated kinase (MAPK) pathway players. The MAPK pathway plays a role in numerous aggressive tumors and has been associated with a subgroup of PHEOs/PGLs, including K-RAS-, RET-, and NF1-mutated tumors. Our aim was to establish whether MAPK signaling may also play a role in aggressive, succinate dehydrogenase (SDH) B mutation-derived PHEOs/PGLs. Expression profiling and western blot analysis indicated that specific aspects of MAPK-signaling are active in SDHB PHEOs/PGLs, suggesting that inhibition by statin treatment could be beneficial. Moreover, we aimed to assess whether the anti-proliferative effect of lovastatin on MPC and MTT differed from that exerted by fluvastatin, simvastatin, atorvastatin, pravastatin, or rosuvastatin. Simvastatin and fluvastatin decreased cell proliferation most effectively and the more aggressive MTT cells appeared more sensitive in this respect. Inhibition of MAPK1 and 3 phosphorylation following treatment with fluvastatin, simvastatin, and lovastatin was confirmed by western blot. Increased levels of CASP-3 and PARP cleavage confirmed induction of apoptosis following the treatment. At a concentration low enough not to affect cell proliferation, spontaneous migration of MPC and MTT was significantly inhibited within 24 hours of treatment. In conclusion, lipophilic statins may present a promising therapeutic option for treatment of aggressive human paragangliomas by inducing apoptosis and inhibiting tumor spread. C1 [Fliedner, Stephanie M. J.; Engel, Tobias; Lendvai, Nikoletta K.; Noelting, Svenja; Pacak, Karel] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Sect Med Neuroendocrinol, Program Reprod & Adult Endocrinol, NIH, Bethesda, MD 20892 USA. [Fliedner, Stephanie M. J.; Ungefroren, Hendrik; Oldoerp, Angela; Lehnert, Hendrik] Univ Med Ctr Schleswig Holstein, Dept Med 1, Lubeck, Germany. [Engel, Tobias; Timmers, Henri] Radboud Univ Nijmegen, Med Ctr, Dept Endocrinol, NL-6525 ED Nijmegen, Netherlands. [Shankavaram, Uma] NCI, Radiat Oncol Branch, NIH, Bethesda, MD 20892 USA. [Noelting, Svenja] Queen Mary Univ London, William Harvey Res Inst, Dept Endocrinol, London, England. [Noelting, Svenja] Queen Mary Univ London, Barts & London Sch Med, Barts Canc Inst, London, England. [Wesley, Robert] NIH, Warren G Magnuson Clin Ctr, Bethesda, MD 20892 USA. [Elkahloun, Abdel G.] NHGRI, Canc Genet Branch, NIH, Bethesda, MD 20892 USA. RP Fliedner, SMJ (reprint author), Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Sect Med Neuroendocrinol, Program Reprod & Adult Endocrinol, NIH, Bethesda, MD 20892 USA. EM Stephanie.fliedner@uksh.de FU Eunice Kennedy Shriver National Institute of Child Health and Human Development; National Human Genome Research Institute, National Institutes of Health, Bethesda, MD, USA; 1st Department of Medicine, University Medical Center Schleswig-Holstein, Lubeck, Germany FX Funding was provided by the Intramural Research Programs of the Eunice Kennedy Shriver National Institute of Child Health and Human Development and the National Human Genome Research Institute, National Institutes of Health, Bethesda, MD, USA and the 1st Department of Medicine, University Medical Center Schleswig-Holstein, Lubeck, Germany. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 54 TC 5 Z9 5 U1 0 U2 10 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA SN 1932-6203 J9 PLOS ONE JI PLoS One PD MAY 20 PY 2014 VL 9 IS 5 AR e97712 DI 10.1371/journal.pone.0097712 PG 9 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA AM0UW UT WOS:000339563400048 PM 24846270 ER PT J AU Martinu, T Kinnier, CV Sun, J Kelly, FL Nelson, ME Garantziotis, S Foster, WM Palmer, SM AF Martinu, Tereza Kinnier, Christine V. Sun, Jesse Kelly, Francine L. Nelson, Margaret E. Garantziotis, Stavros Foster, W. Michael Palmer, Scott M. TI Allogeneic Splenocyte Transfer and Lipopolysaccharide Inhalations Induce Differential T Cell Expansion and Lung Injury: A Novel Model of Pulmonary Graft-versus-Host Disease SO PLOS ONE LA English DT Article ID IDIOPATHIC PNEUMONIA SYNDROME; ALLERGIC AIRWAY INFLAMMATION; INNATE IMMUNE ACTIVATION; BONE-MARROW TRANSPLANT; INHALED LIPOPOLYSACCHARIDE; BRONCHIOLITIS OBLITERANS; DENDRITIC CELLS; HYPERRESPONSIVENESS; MICE; HYPERREACTIVITY AB Background: Pulmonary GVHD (pGVHD) is an important complication of hematopoietic cell transplant (HCT) and is thought to be a consequence of the HCT conditioning regimen, allogeneic donor cells, and posttransplant lung exposures. We have previously demonstrated that serial inhaled lipopolysaccharide (LPS) exposures potentiate the development of pGVHD after murine allogeneic HCT. In the current study we hypothesized that allogeneic lymphocytes and environmental exposures alone, in the absence of a pre-conditioning regimen, would cause features of pGVHD and would lead to a different T cell expansion pattern compared to syngeneic cells. Methods: Recipient Rag1(-/-) mice received a transfer of allogeneic (Allo) or syngeneic (Syn) spleen cells. After 1 week of immune reconstitution, mice received 5 daily inhaled LPS exposures and were sacrificed 72 hours after the last LPS exposure. Lung physiology, histology, and protein levels in bronchoalveolar lavage (BAL) were assessed. Lung cells were analyzed by flow cytometry. Results: Both Allo and Syn mice that undergo LPS exposures (AlloLPS and SynLPS) have prominent lymphocytic inflammation in their lungs, resembling pGVHD pathology, not seen in LPS-unexposed or non-transplanted controls. Compared to SynLPS, however, AlloLPS have significantly increased levels of BAL protein and enhancement of airway hyperreactivity, consistent with more severe lung injury. This injury in AlloLPS mice is associated with an increase in CD8 T cells and effector CD4 T cells, as well as a decrease in regulatory to effector CD4 T cell ratio. Additionally, cytokine analysis is consistent with a preferential Th1 differentiation and upregulation of pulmonary CCL5 and granzyme B. Conclusions: Allogeneic lymphocyte transfer into lymphocyte-deficient mice, followed by LPS exposures, causes features of pGVHD and lung injury in the absence of a pre-conditioning HCT regimen. This lung disease associated with an expansion of allogeneic effector T cells provides a novel model to dissect mechanisms of pGVHD independent of conditioning. C1 [Martinu, Tereza; Kelly, Francine L.; Nelson, Margaret E.; Foster, W. Michael; Palmer, Scott M.] Duke Univ, Med Ctr, Dept Med, Durham, NC 27710 USA. [Kinnier, Christine V.] Massachusetts Gen Hosp, Dept Gen Surg, Boston, MA 02114 USA. [Sun, Jesse] Univ N Carolina, Sch Med, Chapel Hill, NC USA. [Garantziotis, Stavros] NIEHS, Resp Biol Branch, Res Triangle Pk, NC 27709 USA. RP Martinu, T (reprint author), Duke Univ, Med Ctr, Dept Med, Durham, NC 27710 USA. EM tereza.martinu@duke.edu RI Garantziotis, Stavros/A-6903-2009 OI Garantziotis, Stavros/0000-0003-4007-375X FU Parker B. Francis Fellowship Program Award; division of intramural research, NIEHS; [NIH/NHLBI 1P50-HL084917-01]; [NIH 1 K24 HL91140-01A2]; [RR024 127-03] FX This research was supported by the following grants: NIH/NHLBI 1P50-HL084917-01 (SCCOR), Project 3 (SMP), Training core (to TM); NIH 1 K24 HL91140-01A2 (SMP); RR024 127-03 (TM) (KL2); and Parker B. Francis Fellowship Program Award (TM). This research was also supported, in part, by the division of intramural research, NIEHS. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 46 TC 1 Z9 1 U1 0 U2 2 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA SN 1932-6203 J9 PLOS ONE JI PLoS One PD MAY 20 PY 2014 VL 9 IS 5 AR e97951 DI 10.1371/journal.pone.0097951 PG 12 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA AM0UW UT WOS:000339563400074 PM 24844383 ER PT J AU Acuner-Ozbabacan, ES Engin, BH Guven-Maiorov, E Kuzu, G Muratcioglu, S Baspinar, A Chen, Z Van Waes, C Gursoy, A Keskin, O Nussinov, R AF Acuner-Ozbabacan, Ece Saliha Engin, Billur Hatice Guven-Maiorov, Emine Kuzu, Guray Muratcioglu, Serena Baspinar, Alper Chen, Zhong Van Waes, Carter Gursoy, Attila Keskin, Ozlem Nussinov, Ruth TI The structural network of Interleukin-10 and its implications in inflammation and cancer SO BMC GENOMICS LA English DT Article ID PROTEIN-PROTEIN INTERACTIONS; AMYLOID PRECURSOR PROTEIN; HUMAN TISSUE KALLIKREINS; TUMOR-DEVELOPMENT; INTERFACE MOTIFS; IMMUNE-RESPONSE; BREAST-CANCER; IN-VITRO; CELL; RECEPTOR AB Background: Inflammation has significant roles in all phases of tumor development, including initiation, progression and metastasis. Interleukin-10 (IL-10) is a well-known immuno-modulatory cytokine with an anti-inflammatory activity. Lack of IL-10 allows induction of pro-inflammatory cytokines and hinders anti-tumor immunity, thereby favoring tumor growth. The IL-10 network is among the most important paths linking cancer and inflammation. The simple node-and-edge network representation is useful, but limited, hampering the understanding of the mechanistic details of signaling pathways. Structural networks complete the missing parts, and provide details. The IL-10 structural network may shed light on the mechanisms through which disease-related mutations work and the pathogenesis of malignancies. Results: Using PRISM (a PRotein Interactions by Structural Matching tool), we constructed the structural network of IL-10, which includes its first and second degree protein neighbor interactions. We predicted the structures of complexes involved in these interactions, thereby enriching the available structural data. In order to reveal the significance of the interactions, we exploited mutations identified in cancer patients, mapping them onto key proteins of this network. We analyzed the effect of these mutations on the interactions, and demonstrated a relation between these and inflammation and cancer. Our results suggest that mutations that disrupt the interactions of IL-10 with its receptors (IL-10RA and IL-10RB) and alpha 2-macroglobulin (A2M) may enhance inflammation and modulate anti-tumor immunity. Likewise, mutations that weaken the A2M-APP (amyloid precursor protein) association may increase the proliferative effect of APP through preventing beta-amyloid degradation by the A2M receptor, and mutations that abolish the A2M-Kallikrein-13 (KLK13) interaction may lead to cell proliferation and metastasis through the destructive effect of KLK13 on the extracellular matrix. Conclusions: Prediction of protein-protein interactions through structural matching can enrich the available cellular pathways. In addition, the structural data of protein complexes suggest how oncogenic mutations influence the interactions and explain their potential impact on IL-10 signaling in cancer and inflammation. C1 [Acuner-Ozbabacan, Ece Saliha; Engin, Billur Hatice; Guven-Maiorov, Emine; Kuzu, Guray; Muratcioglu, Serena; Baspinar, Alper; Gursoy, Attila; Keskin, Ozlem] Koc Univ, Ctr Computat Biol & Bioinformat, TR-34450 Rumelifeneri Yolu, Sariyer Istanbu, Turkey. [Acuner-Ozbabacan, Ece Saliha; Engin, Billur Hatice; Guven-Maiorov, Emine; Kuzu, Guray; Muratcioglu, Serena; Baspinar, Alper; Gursoy, Attila; Keskin, Ozlem] Koc Univ, Coll Engn, TR-34450 Rumelifeneri Yolu, Sariyer Istanbu, Turkey. [Nussinov, Ruth] Leidos Biomedical Res Inc, Canc & Inflammat Program, Frederick Natl Lab Canc Res, NCI, Frederick, MD 21702 USA. [Chen, Zhong; Van Waes, Carter] Natl Inst Deafness & Commun Disorders, Clin Genom Unit, Head & Neck Surg Branch, NIH, Bethesda, MD 20892 USA. [Nussinov, Ruth] Tel Aviv Univ, Sackler Sch Med, Dept Human Genet & Mol Med, Sackler Inst Mol Med, IL-69978 Tel Aviv, Israel. RP Nussinov, R (reprint author), Leidos Biomedical Res Inc, Canc & Inflammat Program, Frederick Natl Lab Canc Res, NCI, Frederick, MD 21702 USA. EM nussinor@helix.nih.gov RI Gursoy, Attila/E-9565-2015; OI Gursoy, Attila/0000-0002-2297-2113; Guven Maiorov, Emine/0000-0002-7388-9811 FU NIDCD/NIH Intramural projects [Z01-DC-00073, Z01-DC-00074]; Federal funds from the National Cancer Institute, National Institutes of Health [HHSN261200800001E]; Scientific and Technological Research Council of Turkey (TUBITAK) [113E164]; Intramural Research Program of the NIH, National Cancer Institute, Center for Cancer Research FX Zhong Chen and Carter Van Waes are funded by NIDCD/NIH Intramural projects Z01-DC-00073 and Z01-DC-00074. This project has been funded in whole or in part with Federal funds from the National Cancer Institute, National Institutes of Health, under contract number HHSN261200800001E. This work is partially supported by the Scientific and Technological Research Council of Turkey (TUBITAK) Grant Number 113E164. The content of this publication does not necessarily reflect the views or policies of the Department of Health and Human Services, nor does mention of trade names, commercial products, or organizations imply endorsement by the U.S. Government. This research was supported (in part) by the Intramural Research Program of the NIH, National Cancer Institute, Center for Cancer Research. NR 77 TC 11 Z9 13 U1 2 U2 8 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 MAY 20 PY 2014 VL 15 SU 4 AR S2 DI 10.1186/1471-2164-15-S4-S2 PG 17 WC Biotechnology & Applied Microbiology; Genetics & Heredity SC Biotechnology & Applied Microbiology; Genetics & Heredity GA AJ2CR UT WOS:000337463200002 PM 25056661 ER PT J AU Newburger, JW Sleeper, LA Frommelt, PC Pearson, GD Mahle, WT Chen, S Dunbar-Masterson, C Mital, S Williams, IA Ghanayem, NS Goldberg, CS Jacobs, JP Krawczeski, CD Lewis, AB Pasquali, SK Pizarro, C Gruber, PJ Atz, AM Khaikin, S Gaynor, JW Ohye, RG AF Newburger, Jane W. Sleeper, Lynn A. Frommelt, Peter C. Pearson, Gail D. Mahle, William T. Chen, Shan Dunbar-Masterson, Carolyn Mital, Seema Williams, Ismee A. Ghanayem, Nancy S. Goldberg, Caren S. Jacobs, Jeffrey P. Krawczeski, Catherine D. Lewis, Alan B. Pasquali, Sara K. Pizarro, Christian Gruber, Peter J. Atz, Andrew M. Khaikin, Svetlana Gaynor, J. William Ohye, Richard G. CA Pediat Heart Network Investigators TI Transplantation-Free Survival and Interventions at 3 Years in the Single Ventricle Reconstruction Trial SO CIRCULATION LA English DT Article DE cardiac surgical procedures; heart defects, congenital; heart diseases; heart ventricles; Norwood procedures ID AORTOPULMONARY COLLATERAL VESSELS; PULMONARY-ARTERY CONDUIT; BLALOCK-TAUSSIG SHUNT; LEFT-HEART SYNDROME; NORWOOD PROCEDURE; RISK-FACTORS; FONTAN; QUANTIFICATION; OPERATION; MORTALITY AB Background-In the Single Ventricle Reconstruction (SVR) trial, 1-year transplantation-free survival was better for the Norwood procedure with right ventricle-to-pulmonary artery shunt (RVPAS) compared with a modified Blalock-Taussig shunt (MBTS). At 3 years, we compared transplantation-free survival, echocardiographic right ventricular ejection fraction, and unplanned interventions in the treatment groups. Methods and Results-Vital status and medical history were ascertained from annual medical records, death indexes, and phone interviews. The cohort included 549 patients randomized and treated in the SVR trial. Transplantation-free survival for the RVPAS versus MBTS groups did not differ at 3 years (67% versus 61%; P=0.15) or with all available follow-up of 4.8 +/- 1.1 years (log-rank P=0.14). Pre-Fontan right ventricular ejection fraction was lower in the RVPAS group than in the MBTS group (41.7 +/- 5.1% versus 44.7 +/- 6.0%; P=0.007), and right ventricular ejection fraction deteriorated in RVPAS (P=0.004) but not MBTS (P=0.40) subjects (pre-Fontan minus 14-month mean, -3.25 +/- 8.24% versus 0.99 +/- 8.80%; P=0.009). The RVPAS versus MBTS treatment effect had nonproportional hazards (P=0.004); the hazard ratio favored the RVPAS before 5 months (hazard ratio=0.63; 95% confidence interval, 0.45-0.88) but the MBTS beyond 1 year (hazard ratio=2.22; 95% confidence interval, 1.07-4.62). By 3 years, RVPAS subjects had a higher incidence of catheter interventions (P<0.001) with an increasing HR over time (P=0.005): <5 months, 1.14 (95% confidence interval, 0.81-1.60); from 5 months to 1 year, 1.94 (95% confidence interval, 1.02-3.69); and >1 year, 2.48 (95% confidence interval, 1.28-4.80). Conclusions-By 3 years, the Norwood procedure with RVPAS compared with MBTS was no longer associated with superior transplantation-free survival. Moreover, RVPAS subjects had slightly worse right ventricular ejection fraction and underwent more catheter interventions with increasing hazard ratio over time. C1 [Newburger, Jane W.; Dunbar-Masterson, Carolyn] Boston Childrens Hosp, Boston, MA 02115 USA. [Newburger, Jane W.; Dunbar-Masterson, Carolyn] Harvard Univ, Sch Med, Boston, MA USA. [Sleeper, Lynn A.; Chen, Shan] New England Res Inst, Watertown, MA 02172 USA. [Frommelt, Peter C.] Childrens Hosp Wisconsin, Milwaukee, WI 53201 USA. [Frommelt, Peter C.] Med Coll Wisconsin, Milwaukee, WI 53226 USA. [Pearson, Gail D.] NHLBI, NIH, Bethesda, MD 20892 USA. [Mahle, William T.] Emory Univ, Atlanta, GA 30322 USA. [Mital, Seema; Khaikin, Svetlana] Hosp Sick Children, Toronto, ON M5G 1X8, Canada. [Williams, Ismee A.] Morgan Stanley Childrens Hosp New York Presbyteri, New York, NY USA. [Goldberg, Caren S.; Ohye, Richard G.] Univ Michigan, Sch Med, Ann Arbor, MI USA. [Jacobs, Jeffrey P.] Congenital Heart Inst Florida, St Petersburg, FL USA. [Krawczeski, Catherine D.] Cincinnati Childrens Med Ctr, Cincinnati, OH USA. [Lewis, Alan B.] Childrens Hosp Los Angeles, Los Angeles, CA 90027 USA. [Pasquali, Sara K.] Duke Univ, North Carolina Consortium, Durham, NC 27706 USA. [Pasquali, Sara K.] E Carolina Univ, Greenville, NC 27858 USA. [Pasquali, Sara K.] Wake Forest Univ, Winston Salem, NC 27109 USA. [Pizarro, Christian] Nemours Cardiac Ctr, Wilmington, DE USA. [Gruber, Peter J.] Primary Childrens Med Ctr, Salt Lake City, UT 84103 USA. [Gruber, Peter J.] Univ Utah, Salt Lake City, UT USA. [Atz, Andrew M.] Med Univ S Carolina, Charleston, SC USA. [Gaynor, J. William] Childrens Hosp Philadelphia, Philadelphia, PA 19104 USA. [Gaynor, J. William] Univ Penn, Sch Med, Philadelphia, PA 19104 USA. RP Newburger, JW (reprint author), Boston Childrens Hosp, Dept Cardiol, 300 Longwood Ave, Boston, MA 02115 USA. EM jane.newburger@cardio.chboston.org FU National Heart, Lung, and Blood Institute [HL068269, HL068270, HL068279, HL068281, HL068285, HL068288, HL068290, HL068292, HL085057] FX This work was supported by grants (HL068269, HL068270, HL068279, HL068281, HL068285, HL068288, HL068290, HL068292, and HL085057) from the National Heart, Lung, and Blood Institute. This work is solely the responsibility of the authors and does not necessarily represent the official views of the National Heart, Lung, and Blood Institute or National Institutes of Health. NR 21 TC 47 Z9 47 U1 1 U2 2 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 MAY 20 PY 2014 VL 129 IS 20 BP 2013 EP + DI 10.1161/CIRCULATIONAHA.113.006191 PG 25 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA AI6KA UT WOS:000336981400009 PM 24705119 ER PT J AU Mai, PL Loud, JT Greene, MH AF Mai, Phuong L. Loud, Jennifer T. Greene, Mark H. TI A Major Step Forward for BRCA1/2-Related Cancer Risk Management SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Editorial Material ID REDUCING SALPINGO-OOPHORECTOMY; QUALITY-OF-LIFE; BRCA1/2 MUTATION CARRIERS; OVARIAN-CANCER; FALLOPIAN-TUBE; PROPHYLACTIC OOPHORECTOMY; FAMILY-HISTORY; WOMEN; BREAST; CARCINOMA C1 [Mai, Phuong L.; Loud, Jennifer T.; Greene, Mark H.] NCI, NIH, Rockville, MD 20850 USA. RP Mai, PL (reprint author), NCI, NIH, Rockville, MD 20850 USA. NR 35 TC 5 Z9 5 U1 0 U2 1 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X EI 1527-7755 J9 J CLIN ONCOL JI J. Clin. Oncol. PD MAY 20 PY 2014 VL 32 IS 15 BP 1531 EP U21 DI 10.1200/JCO.2013.54.8925 PG 4 WC Oncology SC Oncology GA AI3BI UT WOS:000336733000003 PM 24687832 ER PT J AU Blanch-Hartigan, D Forsythe, LP Alfano, CM Smith, T Nekhlyudov, L Ganz, PA Rowland, JH AF Blanch-Hartigan, Danielle Forsythe, Laura P. Alfano, Catherine M. Smith, Tenbroeck Nekhlyudov, Larissa Ganz, Patricia A. Rowland, Julia H. TI Provision and Discussion of Survivorship Care Plans Among Cancer Survivors: Results of a Nationally Representative Survey of Oncologists and Primary Care Physicians SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article ID FOLLOW-UP CARE; SURVEILLANCE MAMMOGRAPHY; OUTCOMES RESEARCH; PREVENTIVE CARE; PATIENT; COMMUNICATION; QUALITY; VIEWS; GENDER AB Purpose Survivorship care planning should involve discussions between providers and cancer survivors to address survivors' needs and optimize adherence. We examined the frequency and factors associated with oncologists' and primary care physicians' (PCPs) reports of provision of written survivorship care plans (SCPs) and discussion of survivorship care recommendations with survivors. Methods A nationally representative sample of 1,130 oncologists and 1,020 PCPs was surveyed about survivorship care practices with survivors. Logistic regression models predicted multilevel factors associated with providing SCPs or discussing recommendations with survivors. Results Although a majority of oncologists (64%) reported always/almost always discussing survivorship care recommendations with survivors, fewer also discussed who survivors should see for cancer-related and other follow-up care (32%); fewer still also provided a written SCP to the survivor (< 5%). Survivorship care recommendations and provider responsibility were not regularly discussed by PCPs and survivors (12%). Oncologists who reported detailed training about late and long-term effects of cancer were more likely to provide written SCPs (odds ratio [OR], 1.73; 95% CI, 1.22 to 2.44) and discuss survivorship care planning with survivors (OR, 2.02; 95% CI, 1.51 to 2.70). PCPs who received SCPs from oncologists were 9x more likely (95% CI, 5.74 to 14.82) to report survivorship discussions with survivors. Conclusion A minority of both PCPs and oncologists reported consistently discussing and providing SCPs to cancer survivors. Training and knowledge specific to survivorship care and coordinated care between PCPs and oncologists were associated with increased survivorship discussions with survivors. These nationally representative data provide a useful benchmark to assess implementation of new efforts to improve the follow-up care of survivors. (C) 2014 by American Society of Clinical Oncology C1 [Blanch-Hartigan, Danielle; Alfano, Catherine M.; Rowland, Julia H.] NCI, Rockville, MD 20850 USA. [Forsythe, Laura P.] Patient Ctr Outcomes Res Inst, Washington, DC USA. [Smith, Tenbroeck] Amer Canc Soc, Atlanta, GA 30329 USA. [Nekhlyudov, Larissa] Harvard Univ, Sch Med, Boston, MA USA. [Nekhlyudov, Larissa] Harvard Vanguard Med Associates, Boston, MA USA. [Ganz, Patricia A.] Univ Calif Los Angeles, Sch Med, Los Angeles, CA USA. [Ganz, Patricia A.] Univ Calif Los Angeles, Sch Publ Hlth, Los Angeles, CA 90024 USA. RP Blanch-Hartigan, D (reprint author), NCI, Off Canc Survivorship, 9609 Med Ctr Dr,MSC 9764, Rockville, MD 20850 USA. EM danielle.hartigan@nih.gov FU NCI NIH HHS [HHSN261200700068C]; PHS HHS [HHSN261200700068C] NR 38 TC 38 Z9 38 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 MAY 20 PY 2014 VL 32 IS 15 BP 1578 EP 1585 DI 10.1200/JCO.2013.51.7540 PG 8 WC Oncology SC Oncology GA AI3BI UT WOS:000336733000012 PM 24752057 ER PT J AU Andersen, BL DeRubeis, RJ Berman, BS Gruman, J Champion, VL Massie, MJ Holland, JC Partridge, AH Bak, K Somerfield, MR Rowland, JH AF Andersen, Barbara L. DeRubeis, Robert J. Berman, Barry S. Gruman, Jessie Champion, Victoria L. Massie, Mary Jane Holland, Jimmie C. Partridge, Ann H. Bak, Kate Somerfield, Mark R. Rowland, Julia H. TI Screening, Assessment, and Care of Anxiety and Depressive Symptoms in Adults With Cancer: An American Society of Clinical Oncology Guideline Adaptation SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article ID QUALITY-OF-LIFE; PATIENT HEALTH QUESTIONNAIRE; STATE WORRY QUESTIONNAIRE; BREAST-CANCER; MAJOR DEPRESSION; COGNITIVE THERAPY; PSYCHOMETRIC PROPERTIES; SURVIVORSHIP CARE; RATING-SCALE; METAANALYSIS AB Purpose A Pan-Canadian Practice Guideline on Screening, Assessment, and Care of Psychosocial Distress (Depression, Anxiety) in Adults With Cancer was identified for adaptation. Methods American Society of Clinical Oncology (ASCO) has a policy and set of procedures for adapting clinical practice guidelines developed by other organizations. The guideline was reviewed for developmental rigor and content applicability. Results On the basis of content review of the pan-Canadian guideline, the ASCO panel agreed that, in general, the recommendations were clear, thorough, based on the most relevant scientific evidence, and presented options that will be acceptable to patients. However, for some topics addressed in the pan-Canadian guideline, the ASCO panel formulated a set of adapted recommendations based on local context and practice beliefs of the ad hoc panel members. It is recommended that all patients with cancer be evaluated for symptoms of depression and anxiety at periodic times across the trajectory of care. Assessment should be performed using validated, published measures and procedures. Depending on levels of symptoms and supplementary information, differing treatment pathways are recommended. Failure to identify and treat anxiety and depression increases the risk for poor quality of life and potential disease-related morbidity and mortality. This guideline adaptation is part of a larger survivorship guideline series. Conclusion Although clinicians may not be able to prevent some of the chronic or late medical effects of cancer, they have a vital role in mitigating the negative emotional and behavioral sequelae. Recognizing and treating effectively those who manifest symptoms of anxiety or depression will reduce the human cost of cancer. (C) 2014 by American Society of Clinical Oncology C1 [Andersen, Barbara L.] Ohio State Univ, Columbus, OH 43210 USA. [DeRubeis, Robert J.] Univ Penn, Philadelphia, PA 19104 USA. [Berman, Barry S.] Broward Hlth Med Ctr, Ft Lauderdale, FL USA. [Gruman, Jessie] Ctr Adv Hlth, Washington, DC USA. [Champion, Victoria L.] Indiana Univ, Indianapolis, IN 46204 USA. [Massie, Mary Jane; Holland, Jimmie C.] Mem Sloan Kettering Canc Ctr, New York, NY USA. [Partridge, Ann H.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Andersen, Barbara L.; Bak, Kate; Somerfield, Mark R.] Amer Soc Clin Oncol, Alexandria, VA 22314 USA. [Rowland, Julia H.] NCI, Bethesda, MD 20892 USA. RP Andersen, BL (reprint author), Amer Soc Clin Oncol, 2318 Mill Rd,Suite 800, Alexandria, VA 22314 USA. EM guidelines@asco.org FU NCI NIH HHS [K05 CA098133] NR 86 TC 77 Z9 80 U1 10 U2 24 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 MAY 20 PY 2014 VL 32 IS 15 BP 1605 EP U118 DI 10.1200/JCO.2013.52.4611 PG 16 WC Oncology SC Oncology GA AI3BI UT WOS:000336733000015 PM 24733793 ER PT J AU Prasad, V Massey, PR Fojo, T AF Prasad, Vinay Massey, Paul R. Fojo, Tito TI Oral Anticancer Drugs: How Limited Dosing Options and Dose Reductions May Affect Outcomes in Comparative Trials and Efficacy in Patients SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article ID RENAL-CELL CARCINOMA; PHASE-II-TRIAL; METASTATIC BREAST-CANCER; ADVANCED HEPATOCELLULAR-CARCINOMA; RANDOMIZED DISCONTINUATION TRIAL; TYROSINE KINASE INHIBITOR; CHRONIC MYELOID-LEUKEMIA; RESISTANT PROSTATE-CANCER; PROGRESSION-FREE SURVIVAL; MEDULLARY-THYROID CANCER AB Historically, cancer medicine has avoided the problem of unequal dosing by comparing maximum-tolerated doses of intravenous regimens with proportionate dose reductions for toxicity. However, in recent years, with the development of numerous oral anticancer agents, dosing options are arbitrarily and increasingly limited by the size of pills. We contend that an underappreciated consequence of pill size is unequal dosing in comparative clinical trials and that this can have an impact on outcomes. We discuss how comparative effectiveness trials can be unbalanced and how the use of doses that are not sustainable might affect outcomes, especially marginal ones. We further argue that because of their poor tolerability and their limited dosing options, which often result in large dose adjustments in response to toxicity, the real-world clinical effectiveness of oral anticancer agents may be diminished and may not emulate results achieved in registration trials. (C) 2014 by American Society of Clinical Oncology C1 [Prasad, Vinay; Fojo, Tito] NCI, NIH, Bethesda, MD 20892 USA. [Massey, Paul R.] Univ Penn, Perelman Sch Med, Philadelphia, PA 19104 USA. RP Prasad, V (reprint author), NCI, Ctr Canc Res, NIH, Bldg 10,Rm 12N226,9000 Rockville Pike, Bethesda, MD 20892 USA. EM vinayak.prasad@nih.gov NR 111 TC 17 Z9 17 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 MAY 20 PY 2014 VL 32 IS 15 BP 1620 EP U129 DI 10.1200/JCO.2013.53.0204 PG 11 WC Oncology SC Oncology GA AI3BI UT WOS:000336733000016 PM 24711558 ER PT J AU Huang, RK Baxa, U Aldrian, G Ahmed, AB Wall, JS Mizuno, N Antzutkin, O Steven, AC Kajava, AV AF Huang, Rick K. Baxa, Ulrich Aldrian, Gudrun Ahmed, Abdullah B. Wall, Joseph S. Mizuno, Naoko Antzutkin, Oleg Steven, Alasdair C. Kajava, Andrey V. TI Conformational Switching in PolyGln Amyloid Fibrils Resulting from a Single Amino Acid Insertion SO BIOPHYSICAL JOURNAL LA English DT Article ID TRANSMISSION ELECTRON-MICROSCOPY; SOLID-STATE NMR; BETA-SOLENOID PROTEINS; URE2P PRION FILAMENTS; HUNTINGTONS-DISEASE; POLYGLUTAMINE; PARALLEL; IMAGE; FORM; ORGANIZATION AB The established correlation between neurodegenerative disorders and intracerebral deposition of polyglutamine aggregates motivates attempts to better understand their fibrillar structure. We designed polyglutamines with a few lysines inserted to overcome the hindrance of extreme insolubility and two D-lysines to limit the lengths of beta-strands. One is 33 amino acids long (PolyQKd-33) and the other has one fewer glutamine (PolyQKd-32). Both form well-dispersed fibrils suitable for analysis by electron microscopy. Electron diffraction confirmed cross-beta structures in both fibrils. Remarkably, the deletion of just one glutamine residue from the middle of the peptide leads to substantially different amyloid structures. PolyQKd-32 fibrils are consistently 10-20% wider than PolyQKd-33, as measured by negative staining, cryo-electron microscopy, and scanning transmission electron microscopy. Scanning transmission electron microscopy analysis revealed that the PolyQKd-32 fibrils have 50% higher mass-per-length than PolyQKd-33. This distinction can be explained by a superpleated beta-structure model for PolyQKd-33 ;and a model with two beta-solenoid protofibrils for PolyQKd-32. These data provide evidence for beta-arch-containing structures in polyglutamine fibrils and open future possibilities for structure-based drug design. C1 [Huang, Rick K.; Baxa, Ulrich; Mizuno, Naoko; Steven, Alasdair C.] NIAMSD, Struct Biol Lab, NIH, Bethesda, MD 20892 USA. [Baxa, Ulrich] Frederick Natl Lab Canc Res, Electron Microscopy Lab, Canc Res Technol Program, Leidos Biomed Res, Frederick, MD USA. [Aldrian, Gudrun; Ahmed, Abdullah B.; Kajava, Andrey V.] Univ Montpellier 1 & 2, CNRS, Ctr Rech Biochim Macromol, Montpellier, France. [Kajava, Andrey V.] Inst Biol Computat, Montpellier, France. [Kajava, Andrey V.] Univ ITMO, St Petersburg 197101, Russia. [Wall, Joseph S.] Brookhaven Natl Lab, Dept Biol, Upton, NY 11973 USA. [Mizuno, Naoko] Max Planck Inst Biochem, Dept Struct Cell Biol, D-82152 Martinsried, Germany. [Antzutkin, Oleg] Lulea Univ Technol, S-95187 Lulea, Sweden. [Antzutkin, Oleg] Univ Warwick, Dept Phys, Coventry CV4 7AL, W Midlands, England. RP Steven, AC (reprint author), NIAMSD, Struct Biol Lab, NIH, Bethesda, MD 20892 USA. EM stevena@mail.nih.gov; andrey.kajava@crbm.cnrs.fr RI Kajava, Andrey/E-1107-2014 OI Kajava, Andrey/0000-0002-2342-6886 FU intramural research program of National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS); NCI [HHSN261200800001E]; Overseas Scholarship Scheme Phase II grant by the Higher Education Commission of Pakistan FX This work was supported in part by the intramural research program of National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS) and by the NCI under contract HHSN261200800001E, and by an Overseas Scholarship Scheme Phase II grant by the Higher Education Commission of Pakistan to A.B.A. NR 41 TC 2 Z9 2 U1 1 U2 8 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 MAY 20 PY 2014 VL 106 IS 10 BP 2134 EP 2142 DI 10.1016/j.bpj.2014.03.047 PG 9 WC Biophysics SC Biophysics GA AH7ZF UT WOS:000336353200008 PM 24853742 ER PT J AU Wilson, SH AF Wilson, Samuel H. TI The dark side of DNA repair SO ELIFE LA English DT Editorial Material ID HUMAN CANCERS; MUTATIONS C1 NIEHS, Struct Biol Lab, NIH, Res Triangle Pk, NC 27709 USA. RP Wilson, SH (reprint author), NIEHS, Struct Biol Lab, NIH, POB 12233, Res Triangle Pk, NC 27709 USA. EM wilson5@niehs.nih.gov NR 6 TC 1 Z9 1 U1 0 U2 5 PU ELIFE SCIENCES PUBLICATIONS LTD PI CAMBRIDGE PA SHERATON HOUSE, CASTLE PARK, CAMBRIDGE, CB3 0AX, ENGLAND SN 2050-084X J9 ELIFE JI eLife PD MAY 20 PY 2014 VL 3 AR e03068 DI 10.7554/eLife.03068 PG 3 WC Biology SC Life Sciences & Biomedicine - Other Topics GA AH6PM UT WOS:000336253000001 PM 24844708 ER PT J AU Ehrlich, LS Medina, GN Photiadis, S Whittredge, PB Watanabe, S Taraska, JW Carter, CA AF Ehrlich, Lorna S. Medina, Gisselle N. Photiadis, Sara Whittredge, Paul B. Watanabe, Susan Taraska, Justin W. Carter, Carol A. TI Tsg101 regulates P1(4,5)P-2/Ca2+ signaling for HIV-1 Gag assembly SO FRONTIERS IN MICROBIOLOGY LA English DT Article DE HIV-1; Gag assembly; L domain; Tsg101; P1(4,5)P-2; IP3R; Ca2+ signaling; ER-PM junction ID VIRUS TYPE-1 GAG; INOSITOL 1,4,5-TRISPHOSPHATE RECEPTOR; INFECTIOUS-ANEMIA VIRUS; PLASMA-MEMBRANE; INTRACELLULAR TRAFFICKING; TYROSINE PHOSPHORYLATION; MOLECULAR DETERMINANTS; ENDOPLASMIC-RETICULUM; MYRISTATE EXPOSURE; PHOSPHOLIPASE-C AB Our previous studies identified the 1,4,5-inositol trisphosphate receptor (IP3R), a channel mediating release of Ca2+ from ER stores, as a cellular factor differentially associated with HIV-1 Gag that might facilitate ESCRT function in virus budding. Channel opening requires activation that is initiated by binding of 1,4,5-triphosphate (IP3), a product of phospholipase C (PLC)-mediated P1(4,5)P-2 hydrolysis. The store emptying that follows stimulates store refilling which requires intact P1(4,5)P-2. Raising cytosolic Ca2+ promotes viral particle production and our studies indicate that IP3R and the ER Ca2+ store are the physiological providers of Ca2+ for Gag assembly and release. Here, we show that Gag modulates ER store gating and refilling. Cells expressing Gag exhibited a higher cytosolic Ca2+ level originating from the ER store than control cells, suggesting that Gag induced release of store Ca2+. This property required the PTAP motif in Gag that recruits Tsg101, an ESCRT-1 component. Consistent with cytosolic Ca2+ elevation, Gag accumulation at the plasma membrane was found to require continuous IP3R activation. Like other IP3R channel modulators, Gag was detected in physical proximity to the ER and to endogenous IP3R, as indicated respectively by total internal reflection fluorescence (TIRE) and immunoelectron microscopy (IEM) or indirect immunofluorescence. Reciprocal co-immunoprecipitation suggested that Gag and IP3R proximity is favored when the PTAP motif in Gag is intact. Gag expression was also accompanied by increased P1(4,5)P-2 accumulation at the plasma membrane, a condition favoring store refilling capacity. Supporting this notion, Gag particle production was impervious to treatment with 2-aminoethoxydiphenyl borate, an inhibitor of a refilling coupling interaction. In contrast, particle production by a Gag mutant lacking the PTAP motif was reduced. We conclude that a functional PTAP L domain, and by inference Tsg101 binding, confers Gag with an ability to modulate both ER store Ca2+ release and ER store refilling. C1 [Ehrlich, Lorna S.; Medina, Gisselle N.; Photiadis, Sara; Watanabe, Susan; Carter, Carol A.] SUNY Stony Brook, Stony Brook, NY 11794 USA. [Whittredge, Paul B.; Taraska, Justin W.] NHLBI, Lab Mol Biophys, NIH, Bethesda, MD 20892 USA. RP Carter, CA (reprint author), SUNY Stony Brook, Life Sci Bldg Rm 248, Stony Brook, NY 11794 USA. EM carol.carter@stonybrook.edu RI Taraska, Justin/H-8876-2016 OI Taraska, Justin/0000-0001-5355-9535 FU NIH [AI068463, GM111028]; NIAID; intramural research program of the National Heart and Lung Institute, NIH FX We thank Dr. S. Scarlata for instruction and use of instrumentation in her laboratory for Ca2+ measurement. We thank Indralatha Jayatilaka for technical assistance and Susan van Horn and the Stony Brook University Central Microscopy Imaging Electron Microscopy Core Facility for services. This study was supported by the following: NIH R01 awards AI068463 and GM111028 to Carol A. Carter; NIAID ARRA supplemental funding to Carol A. Carter. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. Paul B. Whittredge and Justin W. Taraska are supported by the intramural research program of the National Heart and Lung Institute, NIH. NR 72 TC 1 Z9 1 U1 0 U2 11 PU FRONTIERS RESEARCH FOUNDATION PI LAUSANNE PA PO BOX 110, LAUSANNE, 1015, SWITZERLAND SN 1664-302X J9 FRONT MICROBIOL JI Front. Microbiol. PD MAY 20 PY 2014 VL 5 AR 234 DI 10.3389/fmicb.2014.00234 PG 15 WC Microbiology SC Microbiology GA AH4IN UT WOS:000336090700003 PM 24904548 ER PT J AU Zhang, SP Luo, J Zhu, L Stinchcomb, DG Campbell, D Carter, G Gilkeson, S Feuer, EJ AF Zhang, Shunpu Luo, Jun Zhu, Li Stinchcomb, David G. Campbell, Dave Carter, Ginger Gilkeson, Scott Feuer, Eric J. TI Confidence intervals for ranks of age-adjusted rates across states or counties SO STATISTICS IN MEDICINE LA English DT Article DE age-adjusted rate; rank; simultaneous confidence interval ID BONFERRONI PROCEDURE; MULTIPLE TESTS; LEAGUE TABLES AB Health indices provide information to the general public on the health condition of the community. They can also be used to inform the government's policy making, to evaluate the effect of a current policy or healthcare program, or for program planning and priority setting. It is a common practice that the health indices across different geographic units are ranked and the ranks are reported as fixed values. We argue that the ranks should be viewed as random and hence should be accompanied by an indication of precision (i.e., the confidence intervals). A technical difficulty in doing so is how to account for the dependence among the ranks in the construction of confidence intervals. In this paper, we propose a novel Monte Carlo method for constructing the individual and simultaneous confidence intervals of ranks for age-adjusted rates. The proposed method uses as input age-specific counts (of cases of disease or deaths) and their associated populations. We have further extended it to the case in which only the age-adjusted rates and confidence intervals are available. Finally, we demonstrate the proposed method to analyze US age-adjusted cancer incidence rates and mortality rates for cancer and other diseases by states and counties within a state using a website that will be publicly available. The results show that for rare or relatively rare disease (especially at the county level), ranks are essentially meaningless because of their large variability, while for more common disease in larger geographic units, ranks can be effectively utilized. Copyright (c) 2014 John Wiley & Sons, Ltd. C1 [Zhang, Shunpu] Univ Nebraska, Dept Stat, Lincoln, NE 68583 USA. [Luo, Jun; Campbell, Dave; Carter, Ginger] Informat Management Serv Inc, Calverton, MD 20705 USA. [Zhu, Li; Feuer, Eric J.] NCI, Stat Methodol & Applicat Branch, Div Canc Control & Populat Sci, Bethesda, MD 20892 USA. [Stinchcomb, David G.] Westat Corp, Rockville, MD 20850 USA. RP Zhang, SP (reprint author), Univ Nebraska, Dept Stat, Lincoln, NE 68583 USA. EM szhang3@unl.edu NR 14 TC 4 Z9 4 U1 0 U2 2 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 MAY 20 PY 2014 VL 33 IS 11 BP 1853 EP 1866 DI 10.1002/sim.6071 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 AG7BJ UT WOS:000335572700005 PM 24420973 ER PT J AU Chrispin, J Jain, A Soliman, EZ Guallar, E Alonso, A Heckbert, SR Bluemke, DA Lima, JAC Nazarian, S AF Chrispin, Jonathan Jain, Aditya Soliman, Elsayed Z. Guallar, Eliseo Alonso, Alvaro Heckbert, Susan R. Bluemke, David A. Lima, Joao A. C. Nazarian, Saman TI Association of Electrocardiographic and Imaging Surrogates of Left Ventricular Hypertrophy With Incident Atrial Fibrillation MESA (Multi-Ethnic Study of Atherosclerosis) SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Article DE atrial fibrillation; cardiac magnetic resonance imaging; electrocardiography; left ventricular hypertrophy ID CARDIOVASCULAR MAGNETIC-RESONANCE; II RECEPTOR BLOCKADE; HEART-FAILURE; FOLLOW-UP; HYPERTENSION; DIAGNOSIS; CRITERIA; RISK; MASS; ECHOCARDIOGRAPHY AB Objectives This study sought to examine the association between left ventricular hypertrophy (LVH), defined by cardiac magnetic resonance (CMR) and electrocardiography (ECG), with incident atrial fibrillation (AF). Background Previous studies of the association between AF and LVH were based primarily on echocardiographic measures of LVH. Methods The MESA (Multi-Ethnic Study of Atherosclerosis) enrolled 4,942 participants free of clinically recognized cardiovascular disease. Incident AF was based on MESA-ascertained hospital-discharge International Classification of Diseases codes and Centers for Medicare and Medicaid Services inpatient hospital claims. CMR-LVH was defined as left ventricular mass >= 95th percentile of the MESA population distribution. Eleven ECG-LVH criteria were assessed. The association of LVH with incident AF was evaluated using multivariable Cox proportional hazards models adjusted for CVD risk factors. Results During a median follow-up of 6.9 years, 214 incident AF events were documented. Participants with AF were more likely to be older, hypertensive, and overweight. The risk of AF was greater in participants with CMR-derived LVH (hazard ratio [HR]: 2.04, 95% confidence interval [CI]: 1.15 to 3.62). AF was associated with ECG-derived LVH measure of Sokolow-Lyon voltage product after adjusting for CMR-LVH (HR: 1.83, 95% CI: 1.06 to 3.14, p=0.02). The associations with AF for CMR-LVH and Sokolow-Lyon voltage product were attenuated when adjusted for CMR left atrial volumes. Conclusions In a multiethnic cohort of participants without clinically detected cardiovascular disease, both CMR and ECG-derived LVH were associated with incident AF. ECG-LVH showed prognostic significance independent of CMR-LVH. The association was attenuated when adjusted for CMR left atrial volumes. (C) 2014 by the American College of Cardiology Foundation C1 [Chrispin, Jonathan; Jain, Aditya; Lima, Joao A. C.; Nazarian, Saman] Johns Hopkins Univ, Sch Med, Dept Med, Div Cardiol, Baltimore, MD 21205 USA. [Soliman, Elsayed Z.] Wake Forest Univ, Sch Med, Epidemiol Cardiol Res Ctr EPICARE, Dept Epidemiol, Winston Salem, NC 27109 USA. [Soliman, Elsayed Z.] Wake Forest Univ, Sch Med, Epidemiol Cardiol Res Ctr EPICARE, Dept Prevent & Internal Med,Cardiol Sect, Winston Salem, NC 27109 USA. [Guallar, Eliseo] Johns Hopkins Bloomberg Sch Publ Hlth, Welch Ctr Prevent Epidemiol & Clin Res, Dept Epidemiol, Baltimore, MD USA. [Alonso, Alvaro] Univ Minnesota, Sch Publ Hlth, Dept Epidemiol & Community Hlth, Minneapolis, MN USA. [Heckbert, Susan R.] Univ Washington, Dept Med, Cardiovasc Hlth Res Unit, Seattle, WA USA. [Bluemke, David A.] Natl Inst Biomed Imaging & Bioengn, Ctr Clin, NIH, Bethesda, MD USA. [Bluemke, David A.] Natl Inst Biomed Imaging & Bioengn, Bethesda, MD USA. RP Chrispin, J (reprint author), Div Cardiol, Carnegie 568,600 N Wolfe St, Baltimore, MD 21287 USA. EM chrispin@jhmi.edu RI Alonso, Alvaro/A-4917-2010; OI Alonso, Alvaro/0000-0002-2225-8323; Bluemke, David/0000-0002-8323-8086 FU National Heart, Lung, and Blood Institute [N01-HC-95159, N01-HC-95169]; National Center for Research Resources [UL1-RR-024156, UL1-RR-025005]; National Institutes of Health [K23HL089333, R01HL116280]; Biosense-Webster Incorporated FX This research was supported by contracts N01-HC-95159 through N01-HC-95169 from the National Heart, Lung, and Blood Institute and by grants UL1-RR-024156 and UL1-RR-025005 from the National Center for Research Resources. Dr. Nazarian is supported by grants K23HL089333 and R01HL116280 from the 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. Dr. Nazarian is a scientific advisor and principle investigator for Biosense-Webster Incorporated and has received research funding to Johns Hopkins University from Biosense-Webster Incorporated. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose. Drs. Chrispin and Jain contributed equally to this manuscript. Kristian Wachtell, MD, acted as Guest Editor for this paper. NR 38 TC 11 Z9 13 U1 0 U2 1 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 MAY 20 PY 2014 VL 63 IS 19 BP 2007 EP 2013 DI 10.1016/j.jacc.2014.01.066 PG 7 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA AH1NN UT WOS:000335887800010 PM 24657688 ER PT J AU Zhang, LP Syed, ZA Hard, IV Lim, JM Wells, L Ten Hagen, KG AF Zhang, Liping Syed, Zulfeqhar Ali Hard, Iris van Dijk Lim, Jae-Min Wells, Lance Ten Hagen, Kelly G. TI O-Glycosylation regulates polarized secretion by modulating Tango1 stability SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE mucin; peritrophic membrane; proventriculus; Drosophila; familial tumoral calcinosis ID POLYPEPTIDE N-ACETYLGALACTOSAMINYLTRANSFERASE; FAMILIAL TUMORAL CALCINOSIS; RETICULUM EXIT SITES; UDP-GALNAC; DROSOPHILA-MELANOGASTER; COLLAGEN SECRETION; EXPRESSION; PROTEIN; GLYCOPROTEOME; MUTATIONS AB Polarized secretion is crucial in many tissues. The conserved protein modification, O-glycosylation, plays a role in regulating secretion. However, the mechanisms by which this occurs are unknown. Here, we demonstrate that an O-glycosyltransferase functions as a novel regulator of secretion and secretory vesicle formation in vivo by glycosylating the essential Golgi/endoplasmic reticulum protein, Tango1 (Transport and Golgi organization 1), and conferring protection from furin-mediated proteolysis. Loss of the O-glycosyltransferase PGANT4 resulted in Tango1 cleavage, loss of secretory granules, and disrupted apical secretion. The secretory defects seen upon loss of pgant4 could be rescued either by overexpression of Tango1 or by knockdown of a specific furin (Dfur2) in vivo. Our studies elucidate a novel regulatory mechanism whereby secretion is influenced by the yin/yang of O-glycosylation and proteolytic cleavage. Moreover, our data have broader implications for the potential treatment of diseases resulting from the loss of O-glycosylation by modulating the activity of specific proteases. C1 [Zhang, Liping; Ten Hagen, Kelly G.] Natl Inst Dent & Craniofacial Res, Dev Glycobiol Sect, Lab Cell & Dev Biol, NIH, Bethesda, MD 20892 USA. [Syed, Zulfeqhar Ali] Univ Gothenburg, Inst Biomed, Dept Med Genet, SE-40530 Gothenburg, Sweden. [Hard, Iris van Dijk] Univ Gothenburg, Inst Hlth & Care Sci, SE-40530 Gothenburg, Sweden. [Lim, Jae-Min] Changwon Natl Univ, Dept Chem, Chang Won 641773, Gyeongnam, South Korea. [Lim, Jae-Min; Wells, Lance] Univ Georgia, Complex Carbohydrate Res Ctr, Dept Biochem & Mol Biol, Athens, GA 30602 USA. RP Ten Hagen, KG (reprint author), Natl Inst Dent & Craniofacial Res, Dev Glycobiol Sect, Lab Cell & Dev Biol, NIH, Bethesda, MD 20892 USA. EM Kelly.Tenhagen@nih.gov FU National Institute of Dental and Craniofacial Research, National Institutes of Health [Z01-DE-000713]; National Institutes of Health/National Institute of General Medical Sciences (National Center for Biomedical Glycomics) [P41GM103490]; Basic Science Research Program; Priority Research Centers Program through the National Research Foundation of Korea (NRF) - Ministry of Education, Science and Technology [NRF 2011-0013961, NRF 2010-0029634] FX We thank the members of our laboratory for comments and feedback; Drs. L. Tabak, L. Angerer, and R. Angerer for many helpful discussions and insight; Drs. R. Cummings and T. Ju for the kind gift of the Tn antibody; Drs. L. Fessler and J. Fessler for the kind gift of the papilin antibody; and Drs. J. Kennison and D. Andrew, the Vienna Drosophila RNAi Center, the Bloomington Stock Center, and the Developmental Studies Hybridoma Bank for fly stocks and other reagents. This work was supported by the Intramural Research Program of the National Institute of Dental and Craniofacial Research, National Institutes of Health Grant Z01-DE-000713 (to K. G. T. H.); National Institutes of Health/National Institute of General Medical Sciences (National Center for Biomedical Glycomics, Grant P41GM103490, L. W. Senior Investigator); and the Basic Science Research Program and the Priority Research Centers Program through the National Research Foundation of Korea (NRF) funded by the Ministry of Education, Science and Technology Grants NRF 2011-0013961 and NRF 2010-0029634 (to J.-M.L). NR 38 TC 15 Z9 15 U1 2 U2 13 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD MAY 20 PY 2014 VL 111 IS 20 BP 7296 EP 7301 DI 10.1073/pnas.1322264111 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA AH5KP UT WOS:000336168100037 PM 24799692 ER PT J AU Tal, A Arbel-Goren, R Costantino, N Court, DL Stavans, J AF Tal, Asaf Arbel-Goren, Rinat Costantino, Nina Court, Donald L. Stavans, Joel TI Location of the unique integration site on an Escherichia coli chromosome by bacteriophage lambda DNA in vivo SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE target location; establishment of lysogeny; viral transduction ID SEPARATE CELL HALVES; GENE-TRANSFER; PHAGE-LAMBDA; LIVING CELLS; SEGREGATION; INFECTION; RECOMBINATION; ASSOCIATION; MEMBRANE; PLASMID AB The search for specific sequences on long genomes is a key process in many biological contexts. How can specific target sequences be located with high efficiency, within physiologically relevant times? We addressed this question for viral integration, a fundamental mechanism of horizontal gene transfer driving prokaryotic evolution, using the infection of Escherichia coli bacteria with bacteriophage lambda and following the establishment of a lysogenic state. Following the targeting process in individual live E. coli cells in real time revealed that lambda DNA remains confined near the entry point of a cell following infection. The encounter between the 15-bp-long target sequence on the chromosome and the recombination site on the viral genome is facilitated by the directed motion of bacterial DNA generated during chromosome replication, in conjunction with constrained diffusion of phage DNA. Moving the native bacterial integration site to different locations on the genome and measuring the integration frequency in these strains reveals that the frequencies of the native site and a site symmetric to it relative to the origin are similar, whereas both are significantly higher than when the integration site is moved near the terminus, consistent with the replication-driven mechanism we propose. This novel search mechanism is yet another example of the exquisite coevolution of lambda with its host. C1 [Tal, Asaf; Arbel-Goren, Rinat; Stavans, Joel] Weizmann Inst Sci, Dept Phys Complex Syst, IL-76100 Rehovot, Israel. [Costantino, Nina; Court, Donald L.] NCI, Gene Regulat & Chromosome Biol Lab, Frederick, MD 21702 USA. RP Stavans, J (reprint author), Weizmann Inst Sci, Dept Phys Complex Syst, IL-76100 Rehovot, Israel. EM courtd@mail.nih.gov; joel.stavans@weizmann.ac.il FU Yeda-Sela Center of the Weizmann Institute of Science; National Institutes of Health, National Cancer Institute, Center for Cancer Research FX We thank S. Austin for comments and plasmids, L. Thomason for the gift of lambda strain cI857 bor::kanR, and O. Kobiler, and J. Sawitzke for a careful reading of the manuscript. This work was supported in part by the Yeda-Sela Center of the Weizmann Institute of Science (J. S.), and by the Intramural Research Program of the National Institutes of Health, National Cancer Institute, Center for Cancer Research (D.L.C.). NR 42 TC 9 Z9 9 U1 4 U2 17 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD MAY 20 PY 2014 VL 111 IS 20 BP 7308 EP 7312 DI 10.1073/pnas.1324066111 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA AH5KP UT WOS:000336168100039 PM 24799672 ER PT J AU Yang, GJ Murray, JD Repovs, G Cole, MW Savic, A Glasser, MF Pittenger, C Krystal, JH Wang, XJ Pearlson, GD Glahn, DC Anticevic, A AF Yang, Genevieve J. Murray, John D. Repovs, Grega Cole, Michael W. Savic, Aleksandar Glasser, Matthew F. Pittenger, Christopher Krystal, John H. Wang, Xiao-Jing Pearlson, Godfrey D. Glahn, David C. Anticevic, Alan TI Altered global brain signal in schizophrenia SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE resting-state; global signal; psychiatric illness ID RESTING-STATE FMRI; FUNCTIONAL CONNECTIVITY MRI; DEFAULT NETWORK; WORKING-MEMORY; DYSCONNECTIVITY; DYSFUNCTION; FLUCTUATIONS; REGRESSION; DISORDERS; COGNITION AB Neuropsychiatric conditions like schizophrenia display a complex neurobiology, which has long been associated with distributed brain dysfunction. However, no investigation has tested whether schizophrenia shows alterations in global brain signal (GS), a signal derived from functional MRI and often discarded as a meaningless baseline in many studies. To evaluate GS alterations associated with schizophrenia, we studied two large chronic patient samples (n = 90, n = 71), comparing them to healthy subjects (n = 220) and patients diagnosed with bipolar disorder (n = 73). We identified and replicated increased cortical power and variance in schizophrenia, an effect predictive of symptoms yet obscured by GS removal. Voxel-wise signal variance was also increased in schizophrenia, independent of GS effects. Both findings were absent in bipolar patients, confirming diagnostic specificity. Biologically informed computational modeling of shared and nonshared signal propagation through the brain suggests that these findings may be explained by altered net strength of overall brain connectivity in schizophrenia. C1 [Yang, Genevieve J.; Savic, Aleksandar; Pittenger, Christopher; Krystal, John H.; Pearlson, Godfrey D.; Glahn, David C.; Anticevic, Alan] Yale Univ, Sch Med, Dept Psychiat, New Haven, CT 06511 USA. [Pearlson, Godfrey D.] Yale Univ, Sch Med, Dept Neurobiol, New Haven, CT 06511 USA. [Yang, Genevieve J.; Pittenger, Christopher; Anticevic, Alan] Yale Univ, Interdept Neurosci Program, New Haven, CT 06511 USA. [Pittenger, Christopher; Anticevic, Alan] Yale Univ, Dept Psychol, New Haven, CT 06520 USA. [Yang, Genevieve J.; Savic, Aleksandar; Pittenger, Christopher; Krystal, John H.; Anticevic, Alan] Connecticut Mental Hlth Ctr, Abraham Ribicoff Res Facil, New Haven, CT 06519 USA. [Murray, John D.; Wang, Xiao-Jing] NYU, Ctr Neural Sci, New York, NY USA. [Repovs, Grega] Univ Ljubljana, Dept Psychol, Ljubljana 1000, Slovenia. [Cole, Michael W.] Rutgers State Univ, Ctr Mol & Behav Neurosci, Newark, NJ 07102 USA. [Savic, Aleksandar] Univ Zagreb, Univ Psychiat Hosp Vrapce, Zagreb 10000, Croatia. [Glasser, Matthew F.] Washington Univ, Dept Anat & Neurobiol, St Louis, MO 63130 USA. [Krystal, John H.; Anticevic, Alan] NIAAA, Ctr Translat Neurosci Alcoholism, New Haven, CT 06519 USA. [Wang, Xiao-Jing] New York Univ, New York Univ East China Normal Univ Joint Inst B, Shanghai, Peoples R China. [Pearlson, Godfrey D.; Glahn, David C.] Hartford Hosp, Olin Neuropsychiat Res Ctr, Inst Living, Hartford, CT 06106 USA. RP Anticevic, A (reprint author), Yale Univ, Sch Med, Dept Psychiat, New Haven, CT 06511 USA. EM alan.anticevic@yale.edu RI Murray, John/B-2835-2009; Cole, Michael/G-1056-2010 OI Murray, John/0000-0003-4115-8181; Cole, Michael/0000-0003-4329-438X FU National Institutes of Health [DP50D012109-02, MH080912, MH096801, MH43775, MH077945, MH074797, T32GM 007205]; National Institute on Alcohol Abuse and Alcoholism [2P50AA012870-11]; Fulbright Foundation; National Alliance for Research on Schizophrenia and Depression Young Investigator Award; [R01-MH062349] FX We thank Dr. David Van Essen for helpful comments during manuscript preparation; Dr. Francis Song for assistance with implementing anatomical connectivity into the model; and Dr. Vince Calhoun for assistance with the publicly available Center for Biomedical Research Excellence dataset. Financial support was provided by National Institutes of Health Grants DP50D012109-02 [to A.A., PI (principal investigator)], MH080912 (to D.C.G., PI), MH096801 (to M.W.C., PI), and MH43775, MH077945, and MH074797 (to G.D.P., PI); National Institute on Alcohol Abuse and Alcoholism Grant 2P50AA012870-11 (to J.H.K., PI); the Fulbright Foundation (A.S.); the National Alliance for Research on Schizophrenia and Depression Young Investigator Award (to A.A., PI); Grant R01-MH062349 (to J.D.M. and X.-J.W.); and National Institutes of Health Grant T32GM 007205 (to G.J.Y.). NR 44 TC 60 Z9 60 U1 3 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 MAY 20 PY 2014 VL 111 IS 20 BP 7438 EP 7443 DI 10.1073/pnas.1405289111 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA AH5KP UT WOS:000336168100061 PM 24799682 ER PT J AU Thomson, R Genovese, G Canon, C Kovacsics, D Higgins, MK Carrington, M Winkler, CA Kopp, J Rotimi, C Adeyemo, A Doumatey, A Ayodo, G Alper, SL Pollak, MR Friedman, DJ Raper, J AF Thomson, Russell Genovese, Giulio Canon, Chelsea Kovacsics, Daniella Higgins, Matthew K. Carrington, Mark Winkler, Cheryl A. Kopp, Jeffrey Rotimi, Charles Adeyemo, Adebowale Doumatey, Ayo Ayodo, George Alper, Seth L. Pollak, Martin R. Friedman, David J. Raper, Jayne TI Evolution of the primate trypanolytic factor APOL1 SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID TRYPANOSOME LYTIC FACTOR; DNA-SEQUENCING DATA; HUMAN SERUM; AFRICAN TRYPANOSOMES; BRUCEI-GAMBIENSE; HUMAN GENOME; RESISTANCE; VARIANTS; PROTEIN; ASSOCIATION AB ApolipoproteinL1 (APOL1) protects humans and some primates against several African trypanosomes. APOL1 genetic variants strongly associated with kidney disease in African Americans have additional trypanolytic activity against Trypanosoma brucei rhodesiense, the cause of acute African sleeping sickness. We combined genetic, physiological, and biochemical studies to explore coevolution between the APOL1 gene and trypanosomes. We analyzed the APOL1 sequence in modern and archaic humans and baboons along with geographic distribution in present day Africa to understand how the kidney risk variants evolved. Then, we tested Old World monkey, human, and engineered APOL1 variants for their ability to kill human infective trypanosomes in vivo to identify the molecular mechanism whereby human trypanolytic APOL1 variants evade T. brucei rhodesiense virulence factor serum resistance-associated protein (SRA). For one APOL1 kidney risk variant, a two-residue deletion of amino acids 388 and 389 causes a shift in a single lysine residue that mimics the Old World monkey sequence, which augments trypanolytic activity by preventing SRA binding. A second human APOL1 kidney risk allele, with an amino acid substitution that also restores sequence alignment with Old World monkeys, protected against T. brucei rhodesiense due in part to reduced SRA binding. Both APOL1 risk variants induced tissue injury in murine livers, the site of transgenic gene expression. Our study shows that both genetic variants of human APOL1 that protect against T. brucei rhodesiense have recapitulated molecular signatures found in Old World monkeys and raises the possibility that APOL1 variants have broader innate immune activity that extends beyond trypanosomes. C1 [Thomson, Russell; Canon, Chelsea; Kovacsics, Daniella; Raper, Jayne] NYU, Dept Microbiol, Sch Med, New York, NY 10016 USA. [Genovese, Giulio; Alper, Seth L.; Pollak, Martin R.; Friedman, David J.] Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, Div Renal, Boston, MA 02215 USA. [Friedman, David J.] Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, Ctr Vasc Biol Res, Boston, MA 02215 USA. [Genovese, Giulio; Pollak, Martin R.] Broad Inst Harvard & Massachusetts Inst Technol, Boston, MA 02215 USA. [Canon, Chelsea; Kovacsics, Daniella; Raper, Jayne] CUNY Hunter Coll, Dept Biol Sci, New York, NY 10065 USA. [Higgins, Matthew K.] Univ Oxford, Dept Biochem, Oxford OX1 3QU, England. [Carrington, Mark] Univ Cambridge, Dept Biochem, Cambridge CB2 1QW, England. [Winkler, Cheryl A.] NCI, Basic Res Lab, Ctr Canc Res, NIH,Leidos Biomed Res Inc,Frederick Natl Lab, Frederick, MD 21702 USA. [Kopp, Jeffrey] NIH, Kidney Dis Sect, Bethesda, MD 20892 USA. [Rotimi, Charles; Adeyemo, Adebowale; Doumatey, Ayo] NHGRI, Ctr Res Genom & Global Hlth, NIH, Bethesda, MD 20892 USA. [Ayodo, George] Kenya Govt Med Res Ctr, Kisumu, Kenya. [Ayodo, George] Univ Minnesota, Sch Med, Div Pediat, Minneapolis, MN 55454 USA. RP Friedman, DJ (reprint author), Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, Div Renal, Boston, MA 02215 USA. EM dfriedma@bidmc.harvard.edu; raper@genectr.hunter.cuny.edu OI Kopp, Jeffrey/0000-0001-9052-186X; Higgins, Matthew/0000-0002-2870-1955; Adeyemo, Adebowale/0000-0002-3105-3231 FU National Institutes of Health (NIH)/National Institute of Allergy and Infectious Diseases (NIAID) [R01AI041233]; National Science Foundation [IOS-1249166]; NIH/NIAID Training Grant [T32 AI007180]; NIH/National Institute of Diabetes and Digestive and Kidney Diseases Grant (NIDDK) [DK76868]; Doris Duke Charitable Foundation; Satellite Healthcare Foundation Coplon Award; NIH/National Institue on Minority Health and Health Disparities Grant [R01MD007092]; Wellcome Trust [085256/Z/08/Z, 087692/Z/08/Z]; NIH Intramural Research Program of the Center for Research on Genomics and Global Health [Z01HG200362]; NIH/NIDDK; Doris Duke Clinical Scientist Development Award; National Cancer Institute FX This work was supported by National Institutes of Health (NIH)/National Institute of Allergy and Infectious Diseases (NIAID) Grant R01AI041233 (to J.R.), National Science Foundation Bread Award IOS-1249166 (to J.R.), NIH/NIAID Training Grant T32 AI007180 (to R.T.), NIH/National Institute of Diabetes and Digestive and Kidney Diseases Grant (NIDDK) DK76868 (to D.J.F.), the Doris Duke Charitable Foundation (D.J.F.), Satellite Healthcare Foundation Coplon Award (to D.J.F.), NIH/National Institue on Minority Health and Health Disparities Grant R01MD007092 (to M.R.P.), Wellcome Trust Project Grants 085256/Z/08/Z (to M.C.) and 087692/Z/08/Z (to M.K.H.), NIH Intramural Research Program of the Center for Research on Genomics and Global Health Grant Z01HG200362 (to C.R.), and the NIH/NIDDK and National Cancer Institute Intramural Research Programs (C.A.W. and J.K.). D.J.F. is a recipient of a Doris Duke Clinical Scientist Development Award. NR 46 TC 49 Z9 51 U1 0 U2 20 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 MAY 20 PY 2014 VL 111 IS 20 BP E2130 EP E2139 DI 10.1073/pnas.1400699111 PG 10 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA AH5KP UT WOS:000336168100010 PM 24808134 ER PT J AU Kadri, SS O'Grady, NP AF Kadri, Sameer S. O'Grady, Naomi P. TI Review: Short and long courses of antibiotics do not differ for mortality in ventilator-associated pneumonia SO ANNALS OF INTERNAL MEDICINE LA English DT Editorial Material C1 [Kadri, Sameer S.; O'Grady, Naomi P.] NIH, Ctr Clin, Bethesda, MD 20892 USA. RP Kadri, SS (reprint author), NIH, Ctr Clin, Bethesda, MD 20892 USA. NR 2 TC 0 Z9 0 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 MAY 20 PY 2014 VL 160 IS 10 AR JC3 DI 10.7326/0003-4819-160-10-201405200-02003 PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA AJ0MJ UT WOS:000337347100002 PM 24842437 ER PT J AU Wisniewski, J Hajj, B Chen, JJ Mizuguchi, G Xiao, H Wei, D Dahan, M Wu, C AF Wisniewski, Jan Hajj, Bassam Chen, Jiji Mizuguchi, Gaku Xiao, Hua Wei, Debbie Dahan, Maxime Wu, Carl TI Imaging the fate of histone Cse4 reveals de novo replacement in S phase and subsequent stable residence at centromeres SO ELIFE LA English DT Article DE centromere; kinetochore; Cse4 nucleosome; histone CENP-A; chaperone Scm3; multifocus microscopy; 3D-PALM; photoconvertible fluorescent protein ID BUDDING YEAST KINETOCHORE; SACCHAROMYCES-CEREVISIAE; CENP-A; FISSION YEAST; NONHISTONE SCM3; CHAPERONE SCM3; H3 VARIANT; PROTEIN; NUCLEOSOME; LOCALIZATION AB The budding yeast centromere contains Cse4, a specialized histone H3 variant. Fluorescence pulse-chase analysis of an internally tagged Cse4 reveals that it is replaced with newly synthesized molecules in S phase, remaining stably associated with centromeres thereafter. In contrast, C-terminally-tagged Cse4 is functionally impaired, showing slow cell growth, cell lethality at elevated temperatures and extra-centromeric nuclear accumulation. Recent studies using such strains gave conflicting findings regarding the centromeric abundance and cell cycle dynamics of Cse4. Our findings indicate that internally tagged Cse4 is a better reporter of the biology of this histone variant. Furthermore, the size of centromeric Cse4 clusters was precisely mapped with a new 3D-PALM method, revealing substantial compaction during anaphase. Cse438 specific chaperone Scm3 displays steady-state, stoichiometric co-localization with Cse4 at centromeres throughout the cell cycle, while undergoing exchange with a nuclear pool. These findings suggest that a stable Cse4 nucleosome is maintained by dynamic chaperone-in-residence Scm3. C1 [Wisniewski, Jan; Hajj, Bassam; Chen, Jiji; Mizuguchi, Gaku; Dahan, Maxime; Wu, Carl] Howard Hughes Med Inst, Ashburn, VA 20147 USA. [Wisniewski, Jan; Mizuguchi, Gaku; Xiao, Hua; Wei, Debbie; Wu, Carl] NCI, Biochem & Mol Biol Lab, NIH, Bethesda, MD 20892 USA. RP Wu, C (reprint author), Howard Hughes Med Inst, Janelia Farm Res Campus, Ashburn, VA 20147 USA. EM wisniewskij@janelia.hhmi.org; wuc@janelia.hhmi.org RI Dahan, Maxime /F-1740-2010 FU Center for Cancer Research; NCI; NIH; Janelia Farm Research Campus, HHMI; Fulbright fellowship FX We thank Manjunatha Shivaraju and Jennifer Gerton (Stowers Institute for Medical Research, Kansas City) for the C-terminally tagged Cse4-GFP strain, Gleb Shtengel (Janelia Farm, Ashburn) for advice and preparation of coverslips with immobilized Gold Nanorods, Richard Baker for communicating unpublished results, and Mohamed El Beheiry for use of ViSP software during its development. We are grateful to members of Transcription Imaging Consortium (HHMI Janelia Farm, Ashburn) and our laboratories for helpful discussions. This work was supported by the Center for Cancer Research, NCI, NIH, and the Janelia Farm Research Campus, HHMI. M. D. acknowledges the support of a Fulbright fellowship. NR 63 TC 25 Z9 25 U1 0 U2 0 PU ELIFE SCIENCES PUBLICATIONS LTD PI CAMBRIDGE PA SHERATON HOUSE, CASTLE PARK, CAMBRIDGE, CB3 0AX, ENGLAND SN 2050-084X J9 ELIFE JI eLife PD MAY 20 PY 2014 VL 3 AR e02203 DI 10.7554/eLife.02203 PG 38 WC Biology SC Life Sciences & Biomedicine - Other Topics GA AH6PM UT WOS:000336253000002 PM 24844245 ER PT J AU Abraham, J Robidoux, A Tan, AR Buyse, ME Wolmark, N Jacobs, SA AF Abraham, Jame Robidoux, Andre Tan, Antoinette R. Buyse, Marc E. Wolmark, Norman Jacobs, Samuel A. TI Phase II randomized clinical trial evaluating neoadjuvant chemotherapy regimens with weekly paclitaxel (WP) or eribulin (E) followed by doxorubicin and cyclophosphamide (AC) in women with locally advanced HER2-negative breast cancer (LABC): NSABP FB-9 SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT 50th Annual Meeting of the American-Society-of-Clinical-Oncology CY MAY 30-JUN 03, 2014 CL Chicago, IL SP Amer Soc Clin Oncol C1 Cleveland Clin, Cleveland, OH 44106 USA. NSABP, Montreal, PQ, Canada. Univ Montreal, Ctr Hosp, Montreal, PQ, Canada. NSABP, New Brunswick, NJ USA. Rutgers Canc Inst New Jersey, New Brunswick, NJ USA. Int Inst Drug Dev, Louvain La Neuve, Belgium. NSABP, Pittsburgh, PA USA. Allegheny Gen Hosp, Allegheny Canc Ctr, Pittsburgh, PA 15212 USA. Univ Pittsburgh, Inst Canc, Pittsburgh, PA USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X EI 1527-7755 J9 J CLIN ONCOL JI J. Clin. Oncol. PD MAY 20 PY 2014 VL 32 IS 15 SU S MA 1058 PG 1 WC Oncology SC Oncology GA CN7KL UT WOS:000358613202479 ER PT J AU Allegra, CJ Yothers, G O'Connell, MJ Roh, MS Lopa, SH Petrelli, NJ Beart, RW Sharif, S Wolmark, N AF Allegra, Carmen Joseph Yothers, Greg O'Connell, Michael J. Roh, Mark S. Lopa, Samia H. Petrelli, Nicholas J. Beart, Robert W. Sharif, Saima Wolmark, Norman TI Final results from NSABP protocol R-04: Neoadjuvant chemoradiation (RT) comparing continuous infusion (CIV) 5-FU with capecitabine (Cape) with or without oxaliplatin (Ox) in patients with stage II and III rectal cancer. SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT 50th Annual Meeting of the American-Society-of-Clinical-Oncology CY MAY 30-JUN 03, 2014 CL Chicago, IL SP Amer Soc Clin Oncol C1 Univ Florida, Gainesville, FL USA. NSABP Biostat Ctr, Pittsburgh, PA USA. Univ Pittsburgh, Grad Sch Publ Hlth, Dept Biostat, Pittsburgh, PA 15261 USA. NSABP, Pittsburgh, PA USA. NSABP, Orlando, FL USA. Orlando Hlth, UF Hlth Canc Ctr, Orlando, FL USA. Helen F Graham Canc Ctr & Res Inst, Newark, DE USA. NSABP, Glendale, CA USA. Glendale Mem Hosp, Glendale, CA USA. Allegheny Gen Hosp, Allegheny Canc Ctr, Pittsburgh, PA 15212 USA. NR 0 TC 6 Z9 6 U1 0 U2 0 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 MAY 20 PY 2014 VL 32 IS 15 SU S MA 3603 PG 1 WC Oncology SC Oncology GA CN7KL UT WOS:000358613203119 ER PT J AU Apolo, AB Tomita, Y Lee, MJ Lee, S Frosch, A Steinberg, SM Gulley, JL Schlom, J Bottaro, DP Trepel, JB AF Apolo, Andrea Borghese Tomita, Yusuke Lee, Min-Jung Lee, Sunmin Frosch, Ari Steinberg, Seth M. Gulley, James L. Schlom, Jeffrey Bottaro, Donald P. Trepel, Jane B. TI Effect of cabozantinib on immunosuppressive subsets in metastatic urothelial carcinoma. SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT 50th Annual Meeting of the American-Society-of-Clinical-Oncology CY MAY 30-JUN 03, 2014 CL Chicago, IL SP Amer Soc Clin Oncol C1 NCI, NIH, Bethesda, MD 20892 USA. NCI, Dev Therapeut Branch, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. NIH, Bethesda, MD 20892 USA. NCI, Biostat & Data Management Sect, Ctr Canc Res, Bethesda, MD 20892 USA. NCI, Lab Tumor Immunol & Biol, NIH, Bethesda, MD 20892 USA. NCI, Urol Oncol Branch, Bethesda, MD 20892 USA. RI Gulley, James/K-4139-2016 OI Gulley, James/0000-0002-6569-2912 NR 0 TC 6 Z9 6 U1 0 U2 0 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 MAY 20 PY 2014 VL 32 IS 15 SU S MA 4501 PG 1 WC Oncology SC Oncology GA CN7KL UT WOS:000358613203307 ER PT J AU Apolo, AB Parnes, HL Madan, RA Gulley, JL Trepel, JB Lee, MJ Lee, S Steinberg, SM John, S Velasco, SVA Figg, WD Dahut, WL AF Apolo, Andrea Borghese Parnes, Howard L. Madan, Ravi Amrit Gulley, James L. Trepel, Jane B. Lee, Min-Jung Lee, Sunmin Steinberg, Seth M. John, Simone Velasco, Sylvia Vania Alarcon Figg, William Douglas Dahut, William L. TI A phase I study of gemcitabine, carboplatin, and lenalidomide for treatment of patients with advanced/metastatic urothelial carcinoma (UC) and other solid tumors SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT 50th Annual Meeting of the American-Society-of-Clinical-Oncology CY MAY 30-JUN 03, 2014 CL Chicago, IL SP Amer Soc Clin Oncol C1 NCI, NIH, Bethesda, MD 20892 USA. NCI, Canc Prevent Div, Bethesda, MD 20892 USA. NCI, Dev Therapeut Branch, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. NIH, Bethesda, MD 20892 USA. NCI, Biostat & Data Management Sect, Ctr Canc Res, Bethesda, MD 20892 USA. NCI, Bethesda, MD 20892 USA. NCI, Mol Pharmacol Sect, NIH, Bethesda, MD 20892 USA. RI Gulley, James/K-4139-2016; Figg Sr, William/M-2411-2016 OI Gulley, James/0000-0002-6569-2912; NR 0 TC 0 Z9 0 U1 0 U2 0 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 MAY 20 PY 2014 VL 32 IS 15 SU S MA e15527 PG 1 WC Oncology SC Oncology GA CN7KL UT WOS:000358613200673 ER PT J AU Arnaldez, FI Gombos, E Terwilliger, T Mendoza, A Yeung, C Neckers, L Helman, LJ AF Arnaldez, Fernanda Irene Gombos, Erin Terwilliger, Toby Mendoza, Arnulfo Yeung, Choh Neckers, Len Helman, Lee J. TI Heat-shock protein 90 inhibition in pediatric sarcomas. SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT 50th Annual Meeting of the American-Society-of-Clinical-Oncology CY MAY 30-JUN 03, 2014 CL Chicago, IL SP Amer Soc Clin Oncol C1 NCI, Pediat Oncol Branch, Bethesda, MD 20892 USA. NCI, Bethesda, MD 20892 USA. NCI, Pediat Oncol Branch, CCR, NIH, Bethesda, MD 20892 USA. NCI, Ctr Canc Res, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 MAY 20 PY 2014 VL 32 IS 15 SU S MA 10057 PG 1 WC Oncology SC Oncology GA CN7KL UT WOS:000358613204596 ER PT J AU Ashraf, M Kirkwood, JM Ernstoff, MS Tawbl, HH Frankel, PH Ruel, N Kendra, KL Olencki, T Khushalani, NI Logan, TF Margolin, KA Chen, AP Tarhini, AA AF Ashraf, Madeeha Kirkwood, John M. Ernstoff, Marc S. Abdul-Hassan, Hussein Tawbl Frankel, Paul Henry Ruel, Nora Kendra, Karl Lynn Olencki, Thomas Khushalani, NIkhil I. Logan, Theodore F. Margolin, Kim Allyson Chen, Alice P. Tarhini, Ahmad A. TI NCI 8628: A randomized phase II study of ziv-aflibercept (Z) and high-dose interleukin-2 (HD IL-2) or HD IL-2 alone for inoperable stage III or IV melanoma-Efficacy and biomarker study SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT 50th Annual Meeting of the American-Society-of-Clinical-Oncology CY MAY 30-JUN 03, 2014 CL Chicago, IL SP Amer Soc Clin Oncol C1 Univ Pittsburgh, Inst Canc, Pittsburgh, PA USA. Univ Pittsburgh, Pittsburgh, PA USA. Norris Cotton Canc Ctr, Dartmouth Hitchcock Med Ctr, Lebanon, NH USA. City Hope Natl Med Ctr, Beckman Res Inst, Duarte, CA USA. City Hope Natl Med Ctr, Duarte, CA 91010 USA. Ohio State Univ, Columbus, OH 43210 USA. Roswell Pk Canc Inst, Buffalo, NY 14263 USA. Indiana Univ, Melvin & Bren Simon Canc Ctr, Indianapolis, IN 46204 USA. Univ Washington, Seattle, WA 98195 USA. NCI, Bethesda, MD 20892 USA. Univ Pittsburgh, Med Ctr, Pittsburgh, PA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 MAY 20 PY 2014 VL 32 IS 15 SU S MA TPS9120 PG 1 WC Oncology SC Oncology GA CN7KL UT WOS:000358613202251 ER PT J AU Bae, WK Cho, SH Chung, IJ Furth, PA Hennighausen, L AF Bae, Woo Kyun Cho, Sang-Hee Chung, Ik-Joo Furth, Priscilla A. Hennighausen, Lothar TI The histone methyltransferase EZH2 and breast cancer development: EZH2 and H3K27me3 correlation with prognosis of ER-positive cancers. SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT 50th Annual Meeting of the American-Society-of-Clinical-Oncology CY MAY 30-JUN 03, 2014 CL Chicago, IL SP Amer Soc Clin Oncol C1 NIDDK, NIH, Bethesda, MD 20892 USA. Chonnam Natl Univ, Sch Med, Gwangju, South Korea. Chonnam Natl Univ, Hwasun Hosp, Hwasuneup, South Korea. Georgetown Univ, Washington, DC USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 MAY 20 PY 2014 VL 32 IS 15 SU S MA e11537 PG 1 WC Oncology SC Oncology GA CN7KL UT WOS:000358613200034 ER PT J AU Banerjee, A Jakacki, R Onar-Thomas, A Wu, SJ Nicolaides, T Turner, D Richardson, S Young-Poussaint, T Phillips, JJ Prados, M Packer, R Qaddoumi, IA Gururangan, S Goldman, S Pollack, I Doyle, LA Stewart, CF Boyett, JM Fouladi, M AF Banerjee, Anuradha Jakacki, Regina Onar-Thomas, Arzu Wu, Shengjie Nicolaides, Theodore Turner, David Richardson, Stacye Young-Poussaint, Tina Phillips, Joanna J. Prados, Michael Packer, Roger Qaddoumi, Ibrahim A. Gururangan, Sridharan Goldman, Stewart Pollack, Ian Doyle, L. Austin Stewart, Clinton F. Boyett, James M. Fouladi, Maryam TI A phase I study of AZD6244 in children with recurrent or refractory low-grade gliomas: A Pediatric Brain Tumor Consortium report. SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT 50th Annual Meeting of the American-Society-of-Clinical-Oncology CY MAY 30-JUN 03, 2014 CL Chicago, IL SP Amer Soc Clin Oncol C1 Univ Calif San Francisco, San Francisco, CA 94143 USA. Childrens Hosp Pittsburgh, Pittsburgh, PA 15213 USA. St Jude Childrens Res Hosp, Memphis, TN 38105 USA. Childrens Hosp, Boston, MA 02115 USA. Childrens Natl Med Ctr, Washington, DC 20010 USA. Duke Univ, Med Ctr, Durham, NC USA. Childrens Mem Hosp, Chicago, IL 60614 USA. Childrens Hosp Pittsburgh, Pittsburgh, PA 15213 USA. NCI, Rockville, MD USA. Cincinnati Childrens Hosp Med Ctr, Cincinnati, OH 45229 USA. NR 0 TC 3 Z9 3 U1 0 U2 1 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X EI 1527-7755 J9 J CLIN ONCOL JI J. Clin. Oncol. PD MAY 20 PY 2014 VL 32 IS 15 SU S MA 10065 PG 1 WC Oncology SC Oncology GA CN7KL UT WOS:000358613204604 ER PT J AU Bates, GE Taub, RN Matushansky, I Uldrick, TS Khandker, M Bressler, Y Wang, Y AF Bates, Gleneara Elizabeth Taub, Robert N. Matushansky, Igor Uldrick, Thomas S. Khandker, Maya Bressler, Yaakov Wang, Yi TI A phase I/II study of azacitidine in combination with temozolomide in patients with unresectable or metastatic soft tissue sarcoma or malignant mesothelioma. SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT 50th Annual Meeting of the American-Society-of-Clinical-Oncology CY MAY 30-JUN 03, 2014 CL Chicago, IL SP Amer Soc Clin Oncol C1 Columbia Univ, Med Ctr, New York, NY USA. Novartis Pharmaceut, E Hanover, NJ USA. NCI, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X EI 1527-7755 J9 J CLIN ONCOL JI J. Clin. Oncol. PD MAY 20 PY 2014 VL 32 IS 15 SU S MA 10560 PG 1 WC Oncology SC Oncology GA CN7KL UT WOS:000358613204693 ER PT J AU Bazhenova, L Giaccone, G Nemunaitis, JJ Juhasz, E Ramiau, R van den Heuvel, MM Lal, R Dunlop, D Garon, EB Chu, QS Jain, MM Carrier, E Moses, S Shawler, D Fakhrai, H AF Bazhenova, Lyudmila Giaccone, Giuseppe Nemunaitis, John J. Juhasz, Erzsebet Ramiau, Rodryg van den Heuvel, Michel M. Lal, Rohit Dunlop, David Garon, Edward B. Chu, Quincy S. Jain, Minish Mahendra Carrier, Ewa Moses, Steven Shawler, Daniel Fakhrai, Habib TI An international, multicenter, randomized, double-blind phase III study of maintenance belagenpumatucel-l in non-small cell lung cancer (NSCLC): Updated analysis of patients enrolled within 12 weeks of completion of chemotherapy. SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT 50th Annual Meeting of the American-Society-of-Clinical-Oncology CY MAY 30-JUN 03, 2014 CL Chicago, IL SP Amer Soc Clin Oncol C1 UC San Diego Moores Canc Ctr, La Jolla, CA USA. Georgetown Univ, Washington, DC USA. NCI, Bethesda, MD 20892 USA. Mary Crowley Canc Res Ctr, Dallas, TX USA. Koranyi Natl Inst Pulmonol, Budapest, Hungary. Independent Publ Hlth Care Ctr, Greater Poland Ctr Pulm Dis & TB, Poznan, Poland. Antonie van Leeuwenhoek Hosp, Netherlands Canc Inst, Amsterdam, Netherlands. Guys & St Thomas NHS Fdn Trust, London, England. Glasgow Royal Infirm, Glasgow G4 0SF, Lanark, Scotland. Univ Calif Los Angeles, Los Angeles, CA USA. Cross Canc Ctr, Edmonton, AB, Canada. Noble Hosp, Pune, Maharashtra, India. NovaRx Corp, San Diego, CA USA. NR 0 TC 0 Z9 1 U1 0 U2 0 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 MAY 20 PY 2014 VL 32 IS 15 SU S MA 8056 PG 1 WC Oncology SC Oncology GA CN7KL UT WOS:000358613204119 ER PT J AU Besse, B Garassino, MC Rajan, A Novello, S Mazieres, J Weiss, GJ Ciomei, M Martignoni, M Petroccione, A Davite, C Giaccone, G AF Besse, Benjamin Garassino, Marina Chiara Rajan, Arun Novello, Silvia Mazieres, Julien Weiss, Glen J. Ciomei, Marina Martignoni, Marcella Petroccione, Anna Davite, Cristina Giaccone, Giuseppe TI A phase II study of milciclib (PHA-848125AC) in patients (pts) with thymic carcinoma (TC). SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT 50th Annual Meeting of the American-Society-of-Clinical-Oncology CY MAY 30-JUN 03, 2014 CL Chicago, IL SP Amer Soc Clin Oncol C1 Gustave Roussy, Villejuif, France. Fdn IRCSS Ist Nazl Tumori, Milan, Italy. NCI, NIH, Bethesda, MD 20892 USA. Azienda Osped Univ San Luigi, Orbassano, Italy. Hop De Larrey, Toulouse, France. Goodyear, Canc Treatment Ctr Amer, Western Reg Med Ctr, Scottsdale, AZ USA. Nerviano Med Sci, Nerviano, Italy. CLin Org Strategies & Solut CLIOSS, NMS Grp, Nerviano, Italy. Georgetown Univ, Washington, DC USA. NCI, Bethesda, MD 20892 USA. NR 0 TC 6 Z9 6 U1 0 U2 0 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 MAY 20 PY 2014 VL 32 IS 15 SU S MA 7526 PG 1 WC Oncology SC Oncology GA CN7KL UT WOS:000358613203962 ER PT J AU Better, M Pugach, O Lu, L Somerville, R Kassim, S Kochenderfer, J Rosenberg, SA Marshall, MA Bot, A Nolop, KB Roberts, M Feldman, S AF Better, Marc Pugach, Omar Lu, Lily Somerville, Robert Kassim, Sadik Kochenderfer, James Rosenberg, Steven A. Marshall, Margaret A. Bot, Adrian Nolop, Keith B. Roberts, Margo Feldman, Steven TI Rapid cell expansion (RACE) technology for production of engineered autologons T-cell therapy: Path toward manageable multicenter clinical trials in aggressive NHL with anti-CD19 CAR SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT 50th Annual Meeting of the American-Society-of-Clinical-Oncology CY MAY 30-JUN 03, 2014 CL Chicago, IL SP Amer Soc Clin Oncol C1 Kite Pharma, Santa Monica, CA USA. NCI, Surg Branch, Bethesda, MD 20892 USA. NCI, Expt Transplantat & Immunol Branch, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 1 U2 2 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 MAY 20 PY 2014 VL 32 IS 15 SU S MA 3079 PG 1 WC Oncology SC Oncology GA CN7KL UT WOS:000358613202970 ER PT J AU Bhutani, M Turkbey, B Tan, E Korde, N Kwok, M Manasanch, EE Tageja, N Mailankody, S Roschewski, MJ Mulquin, M Lamping, E Weiss, BM Mena, E Lindenberg, L Calvo, KR Maric, I Choyke, PL Kurdziel, KA Landgren, O AF Bhutani, Manisha Turkbey, Baris Tan, Esther Korde, Neha Kwok, Mary Manasanch, Elisabet E. Tageja, Nishant Mailankody, Sham Roschewski, Mark J. Mulquin, Marcia Lamping, Elizabeth Weiss, Brendan M. Mena, Esther Lindenberg, Liza Calvo, Katherine R. Maric, Irina Choyke, Peter L. Kurdziel, Karen A. Landgren, Ola TI Focal bone marrow processes and early bone lesions in patients with multiple myeloma (MM) precursor diseases: A prospective study using molecular imaging. SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT 50th Annual Meeting of the American-Society-of-Clinical-Oncology CY MAY 30-JUN 03, 2014 CL Chicago, IL SP Amer Soc Clin Oncol C1 NCI, Lymphoid Malignancies Branch, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. NCI, Mol Imaging Program, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. NIH, Hematol Sect, Dept Lab Med, Ctr Canc Res, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 MAY 20 PY 2014 VL 32 IS 15 SU S MA 8587 PG 1 WC Oncology SC Oncology GA CN7KL UT WOS:000358613204266 ER PT J AU Bhutani, M Lee, MJ Tomita, Y Lee, S Frosch, A Carlsten, M Steinberg, SM Korde, N Landgren, O Trepel, JB AF Bhutani, Manisha Lee, Min-Jung Tomita, Yusuke Lee, Sunmin Frosch, Ari Carlsten, Mattias Steinberg, Seth M. Korde, Naha Landgren, Ola Trepel, Jane B. TI Early biomarkers of response to carfilzomib in multiple myeloma (MM.): Modulation of CXCR4 and induction of autophagy SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT 50th Annual Meeting of the American-Society-of-Clinical-Oncology CY MAY 30-JUN 03, 2014 CL Chicago, IL SP Amer Soc Clin Oncol C1 NCI, Lymphoid Malignancies Branch, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. NCI, Dev Therapeut Branch, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. NHLBI, Hematol Branch, NIH, Bethesda, MD 20892 USA. NCI, Biostat & Data Management Sect, Ctr Canc Res, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 MAY 20 PY 2014 VL 32 IS 15 SU S MA e19572 PG 1 WC Oncology SC Oncology GA CN7KL UT WOS:000358613201435 ER PT J AU Bible, KC Suman, VJ Molina, JR Smallridge, RC Maples, WJ Menefee, ME Rubin, J Karlin, NJ Sideras, K Morris, JC McIver, B Hay, ID Fatourechi, V Burton, JK Traynor, AM Flynn, PJ Goh, BC Isham, CR Harris, PJ Erlichman, C AF Bible, Keith Christopher Suman, Vera J. Molina, Julian R. Smallridge, Robert C. Maples, William James Menefee, Michael E. Rubin, Joseph Karlin, Nina J. Sideras, Kostandinos Morris, John C. McIver, Bryan Hay, Ian D. Fatourechi, Vahab Burton, Jill K. Traynor, Anne M. Flynn, Patrick J. Goh, Boon C. Isham, Crescent R. Harris, Pamela Jo Erlichman, Charles TI A multicenter international phase 2 trial of pazopanib in metastatic and progressive medullary thyroid carcinoma: MC057H SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT 50th Annual Meeting of the American-Society-of-Clinical-Oncology CY MAY 30-JUN 03, 2014 CL Chicago, IL SP Amer Soc Clin Oncol C1 Mayo Clin, Rochester, MN USA. Mayo Clin, Jacksonville, FL 32224 USA. Mayo Clin, Scottsdale, AZ USA. Univ Wisconsin, Carbone Canc Ctr, Madison, WI USA. Metro Minnesota Community Clin Oncol Program, St Louis Pk, MN USA. Natl Univ Hlth Syst, Singapore, Singapore. NCI, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 MAY 20 PY 2014 VL 32 IS 15 SU S MA 6026 PG 1 WC Oncology SC Oncology GA CN7KL UT WOS:000358613203618 ER PT J AU Bottaro, DP Lee, YH Agarwal, PK Apolo, AB AF Bottaro, Donald P. Lee, Young H. Agarwal, Piyush K. Apolo, Andrea Borghese TI Met signaling in urothelial carcinoma of the bladder. SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT 50th Annual Meeting of the American-Society-of-Clinical-Oncology CY MAY 30-JUN 03, 2014 CL Chicago, IL SP Amer Soc Clin Oncol C1 NCI, Urol Oncol Branch, Bethesda, MD 20892 USA. NIH, Urol Oncol Branch, NCI, Bethesda, MD 20892 USA. NIH, NCI, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 MAY 20 PY 2014 VL 32 IS 15 SU S MA 4551 PG 1 WC Oncology SC Oncology GA CN7KL UT WOS:000358613203356 ER PT J AU Brancato, SJ Stamatakis, L Apolo, AB Fowler, S Schlom, J Gulley, JL Agarwal, PK AF Brancato, Sam Joseph Stamatakis, Lambros Apolo, Andrea Borghese Fowler, Sarah Schlom, Jeffrey Gulley, James L. Agarwal, Plyush K. TI A randomized, prospective, phase II study to determine the efficacy of BCG given in combination with panvac versus BCG alone in adults with high grade non-muscle invasive bladder cancer who failed at least one induction course of BCG. SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT 50th Annual Meeting of the American-Society-of-Clinical-Oncology CY MAY 30-JUN 03, 2014 CL Chicago, IL SP Amer Soc Clin Oncol C1 NIH, Bethesda, MD 20892 USA. NCI, Urol Oncol Branch, NIH, Bethesda, MD 20892 USA. NCI, Med Oncol Branch, NIH, Bethesda, MD 20892 USA. NCI, Lab Tumor Immunol & Biol, Med Oncol Branch, Bethesda, MD 20892 USA. NCI, NIH, Bethesda, MD 20892 USA. RI Gulley, James/K-4139-2016; Brancato, Sam/K-3266-2014 OI Gulley, James/0000-0002-6569-2912; Brancato, Sam/0000-0002-3760-5818 NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X EI 1527-7755 J9 J CLIN ONCOL JI J. Clin. Oncol. PD MAY 20 PY 2014 VL 32 IS 15 SU S MA TPS4590 PG 1 WC Oncology SC Oncology GA CN7KL UT WOS:000358613202114 ER PT J AU Bunch, KP Noonan, AM Lee, JM O'Sullivan, CCM Houston, ND Ekwede, I Chen, JQ Herrmann, M Cao, L Takebe, N Burns, J Weng, DE Kohn, EC Annunziata, CM AF Bunch, Kristen Paige Noonan, Anne M. Lee, Jung-min O'Sullivan, Ciara Catherine Maria Houston, Nicole D. Ekwede, Irene Chen, Jin-Qiu Herrmann, Michelle Cao, Liang Takebe, Naoko Burns, Jennifer Weng, David Edward Kohn, Elise C. Annunziata, Christina M. TI Pharmacodynamic biomarkers from phase II study of the SMAC (Second Mitochondrial-Derived Activator of Caspases)-mimetic birinapant (TL32711; NSC 756502) in relapsed platinum-resistant epithelial ovarian cancer (EOC), primary peritoneal cancer (PPC), or fallopian tube cancer (FTC) (NCT01681368). SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT 50th Annual Meeting of the American-Society-of-Clinical-Oncology CY MAY 30-JUN 03, 2014 CL Chicago, IL SP Amer Soc Clin Oncol C1 Ctr Canc Res, Womens Malignancies Branch, Bethesda, MD USA. NCI, Med Oncol Branch, Ctr Canc Res, Bethesda, MD 20892 USA. NCI, NIH, Bethesda, MD 20892 USA. NCI, Bethesda, MD 20892 USA. NCI, Collaborat Prot Technol Resource, Cell Biol Lab, Ctr Canc Res,NIH, Bethesda, MD 20892 USA. Canc Therapy Evaluat Program, Invest Drug Branch, Rockville, MD USA. TetraL Pharmaceut, Malvern, PA USA. RI Annunziata, Christina/L-3219-2016 OI Annunziata, Christina/0000-0003-2033-6532 NR 0 TC 0 Z9 0 U1 1 U2 2 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 MAY 20 PY 2014 VL 32 IS 15 SU S MA 5585 PG 1 WC Oncology SC Oncology GA CN7KL UT WOS:000358613203569 ER PT J AU Campian, JL Ye, XB Gladstone, DE Ambady, P Borrello, I Golightly, M Karen, KEK King, E Holdhoff, M Karp, JE Grossman, SA AF Campian, Jian Li Ye, Xiaobu Gladstone, Douglas Edward Ambady, Prakash Borrello, Ivan Golightly, Marc Karen, Karen E. King King, E. Holdhoff, Matthias Karp, Judith E. Grossman, Stuart A. TI Feasibility of lymphocyte harvesting and reinfusion in patients with newly diagnosed high-grade gliomas. SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT 50th Annual Meeting of the American-Society-of-Clinical-Oncology CY MAY 30-JUN 03, 2014 CL Chicago, IL SP Amer Soc Clin Oncol C1 Washington Univ, St Louis, MO USA. Sidney Kimmel Comprehens Canc Ctr Johns Hopkins, Baltimore, MD USA. NCI, Bethesda, MD 20892 USA. Johns Hopkins Univ, Sch Med, Baltimore, MD USA. Stony Brook Med, Stony Brook, NY USA. Johns Hopkins Univ Hosp, Baltimore, MD 21287 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 MAY 20 PY 2014 VL 32 IS 15 SU S MA 2094 PG 1 WC Oncology SC Oncology GA CN7KL UT WOS:000358613202758 ER PT J AU Castro, KM Spain, P Teixeira-Poit, S Das, IP Adjei, BA Siegel, RD Clauser, S Halpern, MT AF Castro, Kathleen M. Spain, Pamela Teixeira-Poit, Stephanie Das, Irene Prabhu Adjei, Brenda A. Siegel, Robert D. Clauser, Steven Halpern, Michael T. TI Sustaining quality cancer care in the NCI Community Cancer Centers Program (NCCCP). SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT 50th Annual Meeting of the American-Society-of-Clinical-Oncology CY MAY 30-JUN 03, 2014 CL Chicago, IL SP Amer Soc Clin Oncol C1 NCI, NIH, Rockville, MD USA. RTI Int, Res Triangle Pk, NC USA. NCI, Div Canc Control & Populat Sci, NIH, Rockville, MD USA. NCI, Rockville, MD USA. Hartford Hosp Helen & Harry Gray Canc Ctr, Hartford, CT USA. Patient Ctr Outcomes Res Inst, Washington, DC USA. RTI Int, Washington, DC USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 MAY 20 PY 2014 VL 32 IS 15 SU S MA 6536 PG 1 WC Oncology SC Oncology GA CN7KL UT WOS:000358613203722 ER PT J AU Chen, EX Winquist, E Ho, C Gitlitz, BJ Ohr, J Razzak, ARA Slu, LL Zwlebel, JA Oza, AM Wang, LS Chin, S Malpage, A Yu, C Mejia, E Gevaudan, L Mohita, P AF Chen, Eric Xueyu Winquist, Eric Ho, Cheryl Gitlitz, Barbara Jennifer Ohr, James Razzak, Albiruni R. A. Slu, Llllian L. Zwlebel, James A. Oza, Amit M. Wang, Lisa Chin, Soo Malpage, Anne Yu, Carleen Mejia, Edward Gevaudan, Lori Mohita, Prachi TI Vorinostat (VOR) and capecitabine (CAP) in recurrent and/or metastatic squamous cell carcinoma ahead and neck (RMHNSCC): A study of the Princess Margaret Phase II Consortium SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT 50th Annual Meeting of the American-Society-of-Clinical-Oncology CY MAY 30-JUN 03, 2014 CL Chicago, IL SP Amer Soc Clin Oncol C1 Princess Margaret Canc Ctr, Toronto, ON, Canada. London Hlth Sci Ctr, London, ON, Canada. British Columbia Canc Agcy, Vancouver, BC V5Z 4E6, Canada. USC Norris Comprehens Canc Ctr, Los Angeles, CA USA. Univ Pittsburgh, Div Hematol Oncol, Pittsburgh, PA USA. Univ Hlth Network, Princess Margaret Canc Ctr, Toronto, ON, Canada. NCI, Rockville, MD USA. Princess Margaret Canc Ctr, Dept Biostat, Toronto, ON, Canada. Princess Margaret Hosp, Toronto, ON M4X 1K9, Canada. BC Canc Agcy, Vancouver, BC, Canada. Univ So Calif, Los Angeles, CA USA. Univ Pittsburgh, Med Ctr, Pittsburgh, PA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 MAY 20 PY 2014 VL 32 IS 15 SU S MA e17001 PG 1 WC Oncology SC Oncology GA CN7KL UT WOS:000358613200911 ER PT J AU Chen, YB Thomas, A Berman, AW Miettinen, M Hassan, R Rajan, A AF Chen, Yuanbin Thomas, Anish Berman, Arlene W. Miettinen, Markku Hassan, Raffit Rajan, Arun TI Mesothelin expression in thymic epithelial tumors (TETs) SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT 50th Annual Meeting of the American-Society-of-Clinical-Oncology CY MAY 30-JUN 03, 2014 CL Chicago, IL SP Amer Soc Clin Oncol C1 [Chen, Yuanbin; Thomas, Anish; Berman, Arlene W.; Miettinen, Markku; Hassan, Raffit; Rajan, Arun] NCI, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 MAY 20 PY 2014 VL 32 IS 15 SU S MA 7607 PG 1 WC Oncology SC Oncology GA CN7KL UT WOS:000358613204065 ER PT J AU Chow, LQM Smith, DC Tan, AR Denlinger, CS Wang, D Shepard, DR Chaudhary, A Lin, Y Koshiji, M AF Chow, Laura Quan Man Smith, David C. Tan, Antoinette R. Denlinger, Crystal Shereen Wang, Ding Shepard, Dale Randall Chaudhary, Archana Lin, Yong Koshiji, Minori TI Phase II study evaluating the effect of concomitant ramucirmamb (IMC-1121B; RAM) on the pharmacokinetics (PK) of paclitaxel (PTX) and the PK of RAM as monotherapy in patients (pts) vth advanced malignant solid tumors. SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT 50th Annual Meeting of the American-Society-of-Clinical-Oncology CY MAY 30-JUN 03, 2014 CL Chicago, IL SP Amer Soc Clin Oncol C1 Univ Washington, Seattle, WA 98195 USA. Univ Michigan, Ctr Comprehens Canc, Ann Arbor, MI 48109 USA. NSABP, New Brunswick, NJ USA. Rutgers Canc Inst New Jersey, New Brunswick, NJ USA. Fox Chase Canc Ctr, Philadelphia, PA 19111 USA. Henry Ford Hlth Syst, Josephine Ford Canc Ctr, Detroit, MI USA. Cleveland Clin, Taussig Canc Inst, Cleveland, OH 44106 USA. Eli Lilly & Co, Indianapolis, IN 46285 USA. ImClone Syst, Bridgewater, NJ USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X EI 1527-7755 J9 J CLIN ONCOL JI J. Clin. Oncol. PD MAY 20 PY 2014 VL 32 IS 15 SU S MA e13554 PG 1 WC Oncology SC Oncology GA CN7KL UT WOS:000358613200244 ER PT J AU Chuk, MK Widemann, BC Ahern, CH Reid, JM Kim, A Wright, JJ Lodish, M Fox, E Weigel, B Blaney, S AF Chuk, Meredith K. Widemann, Brigitte C. Ahern, Charlotte H. Reid, Joel M. Kim, AeRang Wright, John Joseph Lodish, Maya Fox, Elizabeth Weigel, Brenda Blaney, Susan TI A phase I study of cabozantinib (XL184) in children and adolescents with recurrent or refractory solid tumors, including CNS tumors: A Children's Oncology Group phase I consortium trial. SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT 50th Annual Meeting of the American-Society-of-Clinical-Oncology CY MAY 30-JUN 03, 2014 CL Chicago, IL SP Amer Soc Clin Oncol C1 NCI, Pediat Oncol Branch, Bethesda, MD 20892 USA. NCI, Pediat Oncol Branch, NIH, Bethesda, MD 20892 USA. Baylor Coll Med, Houston, TX 77030 USA. Mayo Clin, Dept Oncol, Rochester, MN USA. Childrens Natl Med Ctr, Washington, DC 20010 USA. NCI, Rockville, MD USA. NIH, Bethesda, MD 20892 USA. Childrens Hosp Philadelphia, Philadelphia, PA 19104 USA. Univ Minnesota, Minneapolis, MN USA. Texas Childrens Canc Ctr, Houston, TX USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 MAY 20 PY 2014 VL 32 IS 15 SU S MA 10078 PG 1 WC Oncology SC Oncology GA CN7KL UT WOS:000358613204617 ER PT J AU Collins, KP Geller, DA Marsh, JW Kim, KH Tsung, A Kamarck, T Green, A Santiago, L Kirk, K Labash, C Sun, WJ Buysse, D Steel, JL AF Collins, Kevin P. Geller, David A. Marsh, J. Wallis Kim, Kevin H. Tsung, Allan Kamarck, Thomas Green, Anna Santiago, Lesenia Kirk, Karlie Labash, Chanelle Sun, Weijing Buysse, Daniel Steel, Jennifer Lynne TI Sleep problems and increased risk of mortality in the context of advanced cancer. SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT 50th Annual Meeting of the American-Society-of-Clinical-Oncology CY MAY 30-JUN 03, 2014 CL Chicago, IL SP Amer Soc Clin Oncol C1 Univ Pittsburgh, Pittsburgh, PA USA. NSABP, Pittsburgh, PA USA. Univ Pittsburgh, Med Ctr, Liver Canc Ctr, Pittsburgh, PA USA. UPMC Neuroendocrine Canc Treatment Ctr, Pittsburgh, PA USA. Univ Pittsburgh, Med Ctr, Comprehens Liver Canc Ctr, Pittsburgh, PA USA. Univ Penn, Abramson Canc Ctr, Philadelphia, PA 19104 USA. Univ Pittsburgh, Sch Med, Pittsburgh, PA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 MAY 20 PY 2014 VL 32 IS 15 SU S MA 9649 PG 1 WC Oncology SC Oncology GA CN7KL UT WOS:000358613204533 ER PT J AU Connolly, RM Jankowitz, RC Zahnow, CA Zhang, Z Rudek, MA Slater, S Powers, P Jeter, S Brufsky, A Piekarz, R Herman, JG Ahuja, N Somlo, G Garcia, AA Baylin, S Davidson, NE Stearns, V AF Connolly, Roisin M. Jankowitz, Rachel Catherine Zahnow, Cynthia A. Zhang, Zhe Rudek, Michelle A. Slater, Shannon Powers, Penny Jeter, Stacie Brufsky, Adam Piekarz, Richard Herman, James Gordon Ahuja, Nita Somlo, George Garcia, Agustin A. Baylin, Stephen Davidson, Nancy E. Stearns, Vered TI Phase 2 study investigating the safety, efficacy, and surrogate biomarkers of response to 5-azacitidine (5-AZA) and entinostat in advanced breast cancer SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT 50th Annual Meeting of the American-Society-of-Clinical-Oncology CY MAY 30-JUN 03, 2014 CL Chicago, IL SP Amer Soc Clin Oncol C1 Sidney Kimmel Comprehens Canc Ctr Johns Hopkins, Baltimore, MD USA. Univ Pittsburgh, Med Ctr, Womens Canc Program, Magee Womens Hosp, Pittsburgh, PA USA. Johns Hopkins Univ, Sch Med, Baltimore, MD USA. Sidney Kimmel Comprehens Canc Ctr, Baltimore, MD USA. Univ Pittsburgh, Sch Med, Pittsburgh, PA USA. NCI, Rockville, MD USA. City Hope Canc Ctr, Duarte, CA USA. Univ So Calif, Los Angeles, CA USA. Univ Pittsburgh, Inst Canc, Pittsburgh, PA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 MAY 20 PY 2014 VL 32 IS 15 SU S MA 569 PG 1 WC Oncology SC Oncology GA CN7KL UT WOS:000358613202343 ER PT J AU Denicoff, A Massett, HA Souhan, E Cave, L Welch, JJ Seibel, N Little, RF Mann, BS DiPiazza, K Rossmann, MK Stine, SH Lambersky, R DeSanto, F Fonzi, F Schrag, D Abrams, RA Adelstein, DJ Brown, PD Mooney, MM Abrams, JS AF Denicoff, Andrea Massett, Holly A. Souhan, Erin Cave, Lynn Welch, John J. Seibel, Nita Little, Richard F. Mann, Bhupinder Singh DiPiazza, Kate Rossmann, Megan K. Stine, Sharon Hartson Lambersky, Ruth DeSanto, Frank Fonzi, Frances Schrag, Deborah Abrams, Ross A. Adelstein, David J. Brown, Paul D. Mooney, Margaret M. Abrams, Jeffrey S. TI NCI pilot intervention program to assist accrual for challenging late-phase clinical trials. SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT 50th Annual Meeting of the American-Society-of-Clinical-Oncology CY MAY 30-JUN 03, 2014 CL Chicago, IL SP Amer Soc Clin Oncol C1 NCI, Rockville, MD USA. Emmes Corp, Rockville, MD USA. NCI, Bethesda, MD 20892 USA. NCI, Canc Therapy Evaluat Program, Bethesda, MD 20892 USA. NCI, NIH, Bethesda, MD 20892 USA. EMMES Corp, Rockville, MD USA. Westat Corp, Rockville, MD USA. Radiat Therapy Oncol Grp, Philadelphia, PA USA. Coalit Canc Cooperat Groups, Philadelphia, PA USA. SWOG, Ann Arbor, MI USA. NSABP, Pittsburgh, PA USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Rush Univ, Med Ctr, Chicago, IL 60612 USA. Cleveland Clin, Cleveland, OH 44106 USA. Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 MAY 20 PY 2014 VL 32 IS 15 SU S MA 6617 PG 1 WC Oncology SC Oncology GA CN7KL UT WOS:000358613203801 ER PT J AU Di Fabio, F Rosati, G Lolli, IR Ruggeri, EM Cluffreda, L Ferrari, D Tumolo, S Rostl, G Tralongo, P Ferrara, R Alabiso, O Chiara, S Ianniello, GP Di Costanzo, F Frassoldati, A Iacono, C Clerico, M Pavesl, L Bernardo, G Pinto, C AF Di Fabio, Francesca Rosati, Gerardo Lolli, Ivan Roberto Ruggeri, Enzo Maria Cluffreda, Libero Ferrari, Daris Tumolo, Salvatore Rostl, Giovanni Tralongo, Paolo Ferrara, Raimondo Alabiso, Oscar Chiara, Silvana Ianniello, Giovanni Paolo Di Costanzo, Francesco Frassoldati, Antonio Iacono, Carmelo Clerico, Mario Pavesl, Lorenzo Bernardo, Giovanni Pinto, Carmine TI Italian observational study in patients with metastatic colorectal cancer (mCRC) treated with first-line cetaximab based regimen (ObservEr study) SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT 50th Annual Meeting of the American-Society-of-Clinical-Oncology CY MAY 30-JUN 03, 2014 CL Chicago, IL SP Amer Soc Clin Oncol C1 Orsola Malpighi Hosp, Med Oncol Unit, Bologna, Italy. San Carlo Hosp, Med Oncol Unit, Potenza, Italy. IRCCS Saveri de Bellis, Med Oncol Unit, Castellana Grotte Ba, Italy. Belcolle Hosp, Med Oncol Unit, Viterbo, Italy. Molinette Mauriziano Hosp, Med Oncol Unit, Turin, Italy. San Paolo Hosp, Med Oncol Unit, Milan, Italy. St Maria degli Angeli Hosp, Med Oncol Unit, Pordenone, Italy. Ca Foncello Hosp, Med Oncol Unit, Treviso, Italy. G Di Maria Hosp, Med Oncol Unit, Avola, Italy. Dimiccoli Hosp, Med Oncol Unit, Barletta, Italy. Maggiore della Carita Hosp, Med Oncol Unit, Novara, Italy. Natl Canc Inst, Med Oncol Unit, Genoa, Italy. St Anna & St Sebastian Hosp, Med Oncol Unit, Caserta, Italy. Careggi Hosp, Med Oncol, Florence, Italy. St Anna Hosp, Med Oncol Unit, Ferrara, Italy. M Patemo Hosp, Med Oncol Unit, Ragusa, Italy. Infermi Hosp, Med Oncol Unit, Biella, Italy. IRCCS Salvatore Maugeri Fdn, Med Oncol Unit, Pavia, Italy. IRCCS Maugeri Fdn, Med Oncol Unit, Pavia, Italy. NR 0 TC 0 Z9 0 U1 0 U2 0 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 MAY 20 PY 2014 VL 32 IS 15 SU S MA e14600 PG 1 WC Oncology SC Oncology GA CN7KL UT WOS:000358613200366 ER PT J AU Dimond, EP Zon, R St Germain, DC Denicoff, A Carrigan, A Dempsey, K McCaskill-Stevens, WJ Gonzalez, MM Berger, MZ Gansauer, LJ Bearden, JD Wilkinson, K Bryant, DM Bell, MC Lavasseur, B Stella, P Good, MJ Igo, K Quinones, O Grubbs, SS AF Dimond, Eileen P. Zon, Robin St Germain, Diane C. Denicoff, Andrea Carrigan, Angela Dempsey, Kandie McCaskill-Stevens, Worta J. Gonzalez, Maria Magdalena Berger, Mitchell Z. Gansauer, Lucy Jean Bearden, James D. Wilkinson, Kathy Bryant, Donna M. Bell, Maria Caroline Lavasseur, Beth Stella, Phil Good, Marjorie J. Igo, Kathleen Quinones, Octavio Grubbs, Stephen S. TI The clinical trial assessment of infrastructure matrix tool (CT AIM) to improve the quality of research conduct in the community SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT 50th Annual Meeting of the American-Society-of-Clinical-Oncology CY MAY 30-JUN 03, 2014 CL Chicago, IL SP Amer Soc Clin Oncol C1 NCI, Rockville, MD USA. Michiana Hematol Oncol PC, South Bend, IN USA. Leidos Biomed Res Inc, Frederick, MD USA. Helen F Graham Canc Ctr, Newark, DE USA. St Joseph Hosp, Orange, CA USA. Canc Program Our Lady Lake & Mary Bird Perkins, Baton Rouge, LA USA. Spartanburg Reg Med Ctr, Spartanburg, SC USA. Billings Clin, Billings, MT USA. Sioux Valley Univ Hosp, Sioux Falls, SD USA. St Joseph Mercy Hosp, Ann Arbor, MI 48104 USA. DMS Inc, Frederick Natl Lab Canc Res, Frederick, MD USA. Helen F Graham Canc Ctr Christiana Care, Newark, DE USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X EI 1527-7755 J9 J CLIN ONCOL JI J. Clin. Oncol. PD MAY 20 PY 2014 VL 32 IS 15 SU S MA 6512 PG 2 WC Oncology SC Oncology GA CN7KL UT WOS:000358613203698 ER PT J AU Ding, Y Black, A Hsing, AW Andriole, GL AF Ding, Yan Black, Amanda Hsing, Ann W. Andriole, Gerald L. TI Genetic variant in fragile histidine triad gene (FHIT) and mortality in prostate and breast cancers: Results from the Prostate, Lung, Colon, Ovarian Cancer Screening Trial (PLCO) and Women's Health Initiative (WHI). SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT 50th Annual Meeting of the American-Society-of-Clinical-Oncology CY MAY 30-JUN 03, 2014 CL Chicago, IL SP Amer Soc Clin Oncol C1 City Hope Natl Med Ctr, Duarte, CA USA. NCI, Bethesda, MD 20892 USA. Canc Prevent Inst Calif, Fremont, CA USA. Washington Univ, Sch Med, Barnes Jewish Hosp, St Louis, MO USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 MAY 20 PY 2014 VL 32 IS 15 SU S MA 5076 PG 1 WC Oncology SC Oncology GA CN7KL UT WOS:000358613203468 ER PT J AU Dix, DB Gratias, EJ Seibel, N Anderson, JR Mullen, EA Geller, JI Khanna, G Kalapurakal, JA Perlman, EJ Ehrlich, PF Malogolowkin, MH Grundy, PE Dome, J AF Dix, David B. Gratias, Eric J. Seibel, Nita Anderson, James Robert Mullen, Elizabeth Anne Geller, James I. Khanna, Geetika Kalapurakal, John A. Perlman, Elizabeth Jones Ehrlich, Peter F. Malogolowkin, Marcio H. Grundy, Paul Edward Dome, Jeffrey TI Treatment of stage IV favorable histology Wilms tumor with incomplete lung metastasis response after chemotherapy: A report from Children's Oncology Group study AREN0533. SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT 50th Annual Meeting of the American-Society-of-Clinical-Oncology CY MAY 30-JUN 03, 2014 CL Chicago, IL SP Amer Soc Clin Oncol C1 British Columbia Childrens Hosp, Vancouver, BC V6H 3V4, Canada. TC Thompson Childrens Hosp, Chattanooga, TN USA. NCI, Canc Therapy Evaluat Program, Bethesda, MD 20892 USA. Univ Nebraska Med Ctr, Coll Publ Hlth, Omaha, NE USA. Dana Farber Canc Inst, Boston Childrens Canc & Blood Disorders Ctr, Boston, MA 02115 USA. Cincinnati Childrens Hosp Med Ctr, Cincinnati, OH 45229 USA. Washington Univ, Sch Med, St Louis, MO USA. Northwestern Memor Hosp, Chicago, IL USA. Northwestern Univ, Feinberg Sch Med, Ann & Robert H Lurie Childrens Hosp Chicago, Chicago, IL 60611 USA. Univ Michigan, Ann Arbor, MI 48109 USA. Midwest Childrens Canc Ctr, Milwaukee, WI USA. Stollery Childrens Hosp, Edmonton, AB, Canada. Childrens Natl Med Ctr, Washington, DC 20010 USA. NR 0 TC 1 Z9 1 U1 0 U2 0 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 MAY 20 PY 2014 VL 32 IS 15 SU S MA 10001 PG 1 WC Oncology SC Oncology GA CN7KL UT WOS:000358613204540 ER PT J AU Do, KT Wilsker, D Balasubramanian, P Zlott, J Jeong, W Lawrence, SM Kinders, RJ Collins, J Chen, AP Doroshow, JH Kummar, S AF Do, Khanh Tu Wilsker, Deborah Balasubramanian, Priya Zlott, Jennifer Jeong, Woondong Lawrence, Scott M. Kinders, Robert J. Collins, Jerry Chen, Alice P. Doroshow, James H. Kummar, Shivaani TI Phase I trial of AZD1775 (MK1775), a wee1 kinase inhibitor, in patients with refractory solid tumors SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT 50th Annual Meeting of the American-Society-of-Clinical-Oncology CY MAY 30-JUN 03, 2014 CL Chicago, IL SP Amer Soc Clin Oncol C1 NCI, Ctr Canc Res, Bethesda, MD 20892 USA. NCI, Frederick, MD 21701 USA. NCI, Div Canc Treatment & Diag, Bethesda, MD 20892 USA. SAIC Frederick Inc, Frederick, MD USA. Leidos Biomed Res Inc, Frederick Natl Lab Canc Res, Frederick, MD USA. NCI, Rockville, MD USA. NCI, Bethesda, MD 20892 USA. NR 0 TC 1 Z9 1 U1 1 U2 2 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 MAY 20 PY 2014 VL 32 IS 15 SU S MA 2503 PG 1 WC Oncology SC Oncology GA CN7KL UT WOS:000358613202768 ER PT J AU Dosani, T Korde, N Manasanch, EE Bhutani, M Tageja, N Mailankody, S Roschewski, MJ Kwok, M Kazandjian, DG Landgren, O Maric, I AF Dosani, Talib Korde, Neha Manasanch, Elisabet Esteve Bhutani, Manisha Tageja, Nishant Mailankody, Sham Roschewski, Mark J. Kwok, Mary Kazandjian, Dickran Gano Landgren, Ola Maric, Irina TI Large granular lymphocyte (LGL) subsets in smoldering multiple myeloma (SMM): Immunophenotypic profiles that predict progression to multiple myeloma (MM). SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT 50th Annual Meeting of the American-Society-of-Clinical-Oncology CY MAY 30-JUN 03, 2014 CL Chicago, IL SP Amer Soc Clin Oncol C1 NCI, Lymphoid Malignancies Branch, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. NIH, Hematol Sect, Dept Lab Med, Ctr Canc Res, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 MAY 20 PY 2014 VL 32 IS 15 SU S MA 8597 PG 1 WC Oncology SC Oncology GA CN7KL UT WOS:000358613204275 ER PT J AU Dueck, AC Hillman, DW Kottschade, LA Halyard, MY Sloan, JA Flickinger, LM Wolff, AC Harris, L Gralow, J Pritchard, KI Ellard, S Le-Lindqwister, N Boyle, FM De Azambuja, E McCaskill-Stevens, WJ Zujewski, JA Piccart-Gebhart, MJ Perez, EA AF Dueck, Amylou C. Hillman, David W. Kottschade, Lisa A. Halyard, Michele Y. Sloan, Jeff A. Flickinger, Lynn M. Wolff, Antonio C. Harris, Lyndsay Gralow, Julie Pritchard, Kathleen I. Ellard, Susan Le-Lindqwister, Nguyet Boyle, Frances M. De Azambuja, Evandro McCaskill-Stevens, Worta J. Zujewski, Jo Anne Piccart-Gebhart, Martine J. Perez, Edith A. TI Quality of life (QOL) among patients (pts) with HER2+breast cancer (bc) treated with adjuvant lapatinib and/or trastuzumab in the ALTTO study (BIG 2-06, Alliance N063D). SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT 50th Annual Meeting of the American-Society-of-Clinical-Oncology CY MAY 30-JUN 03, 2014 CL Chicago, IL SP Amer Soc Clin Oncol C1 Mayo Clin, Scottsdale, AZ USA. Mayo Clin, Alliance Stat & Data Ctr, Rochester, MN USA. Mayo Clin, Rochester, MN USA. Johns Hopkins Univ Hosp, Baltimore, MD 21287 USA. Sidney Kimmel Comprehens Canc Ctr Johns Hopkins, Baltimore, MD USA. Case Western Seidman Canc Ctr, Cleveland, OH USA. Seattle Canc Care Alliance, Seattle, WA USA. Sunnybrook Odette Canc Ctr, Toronto, ON, Canada. Univ Toronto, Toronto, ON, Canada. British Columbia Canc Agcy, Ctr Southern Interior, Kelowna, BC, Canada. Illinois CancerCare Peoria, Peoria, IL USA. Patricial Rigchie Ctr Canc Care & Res, Sydney, NSW, Australia. Univ Libre Bruxelles, Inst Jules Bordet, Brussels, Belgium. NCI, Rockville, MD USA. NCI, Bethesda, MD 20892 USA. Inst Jules Bordet, Breast Int Grp, B-1000 Brussels, Belgium. Mayo Clin, Jacksonville, FL 32224 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 MAY 20 PY 2014 VL 32 IS 15 SU S MA 647 PG 1 WC Oncology SC Oncology GA CN7KL UT WOS:000358613202420 ER PT J AU Duffy, AG Ulahannan, SV Fioravanti, S Walker, M Figg, WD Compton, K Venkatesan, A Abi-Jaoudoh, N Wood, BJ Greten, TF AF Duffy, Austin G. Ulahannan, Susanna Varkey Fioravanti, Suzanne Walker, Melissa Figg, William Douglas Compton, Kathryn Venkatesan, Aradhana Abi-Jaoudoh, Nadine Wood, Bradford J. Greten, Tim F. TI A pilot study of tremelimumab, a monoclonal antibody against CTLA-4, in combination with either trans catheter arterial chemoembolization (TACE) or radiofrequency ablation (RFA) in patients with hepatocellular carcinoma (HCC) SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT 50th Annual Meeting of the American-Society-of-Clinical-Oncology CY MAY 30-JUN 03, 2014 CL Chicago, IL SP Amer Soc Clin Oncol C1 NCI, NIH, Bethesda, MD 20892 USA. NCI, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. NCI, Mol Pharmacol Sect, NIH, Bethesda, MD 20892 USA. NCI, Ctr Intervent Oncol, Bethesda, MD 20892 USA. NIH, Ctr Clin, Bethesda, MD 20892 USA. RI Figg Sr, William/M-2411-2016 NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X EI 1527-7755 J9 J CLIN ONCOL JI J. Clin. Oncol. PD MAY 20 PY 2014 VL 32 IS 15 SU S MA e15133 PG 1 WC Oncology SC Oncology GA CN7KL UT WOS:000358613200532 ER PT J AU EI-Khoueiry, AB O'Donnell, R Mack, PC Blanchard, S Bahary, N Jiang, YX Wright, JJ Chen, HX Lenz, HJ Gandara, DR AF EI-Khoueiry, Anthony B. O'Donnell, Robert Mack, Philip C. Blanchard, Suzette Bahary, Nathan Jiang, Yixing Wright, John Joseph Chen, Helen X. Lenz, Heinz-Josef Gandara, David R. TI A phase I trial of of cixutumumab (C) (IMC-A12) and sorafenib (S) for treatment of advanced hepatocellular carcinoma (HCC). SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT 50th Annual Meeting of the American-Society-of-Clinical-Oncology CY MAY 30-JUN 03, 2014 CL Chicago, IL SP Amer Soc Clin Oncol C1 USC Norris Comprehens Canc Ctr, Los Angeles, CA USA. Univ Calif Davis, Sacramento, CA 95817 USA. UC Davis Comprehens Canc Ctr, Sacramento, CA USA. City Hope Natl Med Ctr, Duarte, CA USA. Univ Pittsburgh, Med Ctr, Pittsburgh, PA USA. Univ Maryland, Baltimore, MD 21201 USA. NCI, Rockville, MD USA. NCI, Canc Therapy Evaluat Program, Rockville, MD USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X EI 1527-7755 J9 J CLIN ONCOL JI J. Clin. Oncol. PD MAY 20 PY 2014 VL 32 IS 15 SU S MA 4105 PG 1 WC Oncology SC Oncology GA CN7KL UT WOS:000358613203268 ER PT J AU Folio, L Derderian, V Steinberg, SM Turkbey, E Apolo, AB AF Folio, Les Derderian, Vana Steinberg, Seth M. Turkbey, Evrim Apolo, Andrea Borghese TI Assessing tumor response using CT density-volume trajectory in metastatic bladder cancer. SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT 50th Annual Meeting of the American-Society-of-Clinical-Oncology CY MAY 30-JUN 03, 2014 CL Chicago, IL SP Amer Soc Clin Oncol C1 NIH, Radiol & Imaging Sci, Bethesda, MD 20892 USA. NCI, Biostat & Data Management Sect, Ctr Canc Res, Bethesda, MD 20892 USA. NIH, NCI, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X EI 1527-7755 J9 J CLIN ONCOL JI J. Clin. Oncol. PD MAY 20 PY 2014 VL 32 IS 15 SU S MA 4539 PG 1 WC Oncology SC Oncology GA CN7KL UT WOS:000358613203344 ER PT J AU Forde, PM Hooker, CM Rubinstein, L Hann, CL Harris, PJ AF Forde, Patrick M. Hooker, Craig M. Rubinstein, Larry Hann, Christine L. Harris, Pamela Jo TI Analysis of small cell lung cancer (SCLC) patients (Pts) treated on cancer therapy evaluation program (CTEP)-sponsored phase I trials: 1992-2012. SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT 50th Annual Meeting of the American-Society-of-Clinical-Oncology CY MAY 30-JUN 03, 2014 CL Chicago, IL SP Amer Soc Clin Oncol C1 Sidney Kimmel Comprehens Canc Ctr Johns Hopkins, Baltimore, MD USA. Biometr Res Branch, Bethesda, MD USA. NCI, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 MAY 20 PY 2014 VL 32 IS 15 SU S MA 7524 PG 1 WC Oncology SC Oncology GA CN7KL UT WOS:000358613203960 ER PT J AU Fukuda, YK Huang, E Finnigan, S Ivy, SP Rubinstein, L Takebe, N AF Fukuda, Yoko Korenaga Huang, Erich Finnigan, Shanda Ivy, S. Percy Rubinstein, Larry Takebe, Naoko TI Risks and benefits of phase 1 oncology trials, 2001 through 2012. SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT 50th Annual Meeting of the American-Society-of-Clinical-Oncology CY MAY 30-JUN 03, 2014 CL Chicago, IL SP Amer Soc Clin Oncol C1 MedStar Washington Hosp Ctr, Washington, DC USA. NCI, Div Canc Treatment & Diag, Biometr Res Branch, Rockville, MD USA. NCI, Rockville, MD USA. NCI, Canc Therapy Evaluat Program, Bethesda, MD 20892 USA. Div Canc Treatment & Diag, Bethesda, MD USA. Canc Therapy Evaluat Program, Invest Drug Branch, Rockville, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 MAY 20 PY 2014 VL 32 IS 15 SU S MA 2552 PG 1 WC Oncology SC Oncology GA CN7KL UT WOS:000358613202817 ER PT J AU Garin, SS Robinson, P Juarez, P Pan, DY Hays, R AF Garin, Sherri Sheinfeld Robinson, Paul Juarez, Paul Pan, Deyu Hays, Ron TI The impact of place on health-related quality of life among US cancer survivors SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT 50th Annual Meeting of the American-Society-of-Clinical-Oncology CY MAY 30-JUN 03, 2014 CL Chicago, IL SP Amer Soc Clin Oncol C1 NCI SAIC, New York, NY USA. Chades R Drew Hlth Sci Univ, Los Angeles, CA USA. Univ Calif Los Angeles, Los Angeles, CA USA. Univ Tennessee, Ctr Hlth Sci, Memphis, TN 38163 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 MAY 20 PY 2014 VL 32 IS 15 SU S MA e17642 PG 1 WC Oncology SC Oncology GA CN7KL UT WOS:000358613201100 ER PT J AU Ghafoor, A Calvo, KR Corrigan-Cummins, M Simakova, O Costello, R Yuan, C Stetler-Stevenson, M Korde, N Roschewski, MJ Landgren, O Maric, I AF Ghafoor, Azam Calvo, Katherine R. Corrigan-Cummins, Meghan Simakova, Olga Costello, Rene Yuan, Constance Stetler-Stevenson, Maryallce Korde, Neha Roschewski, Mark J. Landgren, Ola Maric, Irina TI Immunephenotypic profiles of plasma cells and tumor burden in patients with smoldering myeloma (SMM) and monoclonal gammopathy of undetermined significance (MGUS) SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT 50th Annual Meeting of the American-Society-of-Clinical-Oncology CY MAY 30-JUN 03, 2014 CL Chicago, IL SP Amer Soc Clin Oncol C1 NIH, Hematol Sect, Dept Lab Med, Ctr Clin, Bethesda, MD 20892 USA. NIH, Hematol Sect, Dept Lab Med, Ctr Canc Res, Bethesda, MD 20892 USA. NCI, Multiple Myeloma Sect, Metab Branch, Ctr Canc Res, Bethesda, MD 20892 USA. NCI, Pathol Lab, CCR, NIH, Bethesda, MD 20892 USA. NCI, Pathol Lab, NIH, Bethesda, MD 20892 USA. NCI, Lymphoid Malignancies Branch, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 MAY 20 PY 2014 VL 32 IS 15 SU S MA e19589 PG 1 WC Oncology SC Oncology GA CN7KL UT WOS:000358613201447 ER PT J AU Giamanco, NM Jee, YH Shriver, CD Summers, TA Wellstein, A Baron, J AF Giamanco, Nicole Michelle Jee, Youn Hee Shriver, Craig D. Summers, Thomas A. Wellstein, Anton Baron, Jeffrey TI Midkine and pleiotrophin concentrations in biopsy needle washout of breast masses. SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT 50th Annual Meeting of the American-Society-of-Clinical-Oncology CY MAY 30-JUN 03, 2014 CL Chicago, IL SP Amer Soc Clin Oncol C1 Walter Reed Natl Mil Med Ctr, Dept Pediat, Bethesda, MD USA. NICHHD, Dev Endocrinol & Genet, NIH, Bethesda, MD 20892 USA. Walter Reed Natl Mil Med Ctr, John P Murtha Canc Ctr, Bethesda, MD USA. Walter Reed Natl Mil Med Ctr, Dept Pathol & Lab Serv, Bethesda, MD USA. Georgetown Univ, Lombardi Comprehens Canc Ctr, Washington, DC USA. NICHHD, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 MAY 20 PY 2014 VL 32 IS 15 SU S MA e22104 PG 1 WC Oncology SC Oncology GA CN7KL UT WOS:000358613201836 ER PT J AU Glynn, SA Wallace, T Downey, R Seufert, C Schetter, A Giles, FJ Sullivan, F Dorsey, T Goldman, R Yan, PS Wang-Johanning, F Ambs, S AF Glynn, Sharon A. Wallace, Tiffany Downey, Ronan Seufert, Caleb Schetter, Aaron Giles, Francis J. Sullivan, Frank Dorsey, Tiffany Goldman, Radoslav Yan, Peisha Wang-Johanning, Feng Ambs, Stefan TI The potential of peripheral blood HERV-K expression as a biomarker for diagnosis with prostate cancer in older men. SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT 50th Annual Meeting of the American-Society-of-Clinical-Oncology CY MAY 30-JUN 03, 2014 CL Chicago, IL SP Amer Soc Clin Oncol C1 Natl Univ Ireland Galway, Prostate Canc Inst, Galway, Ireland. NCI, Bethesda, MD 20892 USA. Natl Univ Ireland Galway, Galway, Ireland. Natl Univ Ireland, HRB Clin Res Facil, Dublin, Ireland. Univ Dublin Trinity Coll, Dublin 2, Ireland. Galway Univ Hosp, Galway, Ireland. Georgetown Univ, Lombardi Comprehens Canc Ctr, Washington, DC USA. Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA. SRI Int, Menlo Pk, CA 94025 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 MAY 20 PY 2014 VL 32 IS 15 SU S MA 5049 PG 1 WC Oncology SC Oncology GA CN7KL UT WOS:000358613203441 ER PT J AU Good, MJ Hurley, PA Mesfin, E AF Good, Marjorie J. Hurley, Patricia A. Mesfin, Eden TI The road to assessing clinical trial-associated workload SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT 50th Annual Meeting of the American-Society-of-Clinical-Oncology CY MAY 30-JUN 03, 2014 CL Chicago, IL SP Amer Soc Clin Oncol C1 NCI, Rockville, MD USA. Amer Soc Clin Oncol, Alexandria, VA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 MAY 20 PY 2014 VL 32 IS 15 SU S MA e17587 PG 1 WC Oncology SC Oncology GA CN7KL UT WOS:000358613201051 ER PT J AU Gucalp, A Morris, PG Zhou, XK Giri, DD Iyengar, NM Crew, KD Hershman, DL Garber, JE Nangla, JR Cook, ED Vornik, L Dunn, BK Heckman-Stoddard, BM Foster, K Brown, P Dannenberg, A Hudis, CA AF Gucalp, Ayca Morris, Patrick Glyn Zhou, Xi Kathy Giri, Dilip D. Iyengar, Neil M. Crew, Katherine D. Hershman, Dawn L. Garber, Judy Ellen Nangla, Julie R. Cook, Elise D. Vornik, Lana Dunn, Barbara Karen Heckman-Stoddard, Brandy M. Foster, Kathleen Brown, Powel Dannenberg, Andrew Hudis, Clifford A. CA UT MD Anderson Early Phase TI A multicenter phase II study of docosahexaenoic acid (DHA) in patients (pts) with a history of breast cancer (BC), premalignant lesions, or benign breast disease SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT 50th Annual Meeting of the American-Society-of-Clinical-Oncology CY MAY 30-JUN 03, 2014 CL Chicago, IL SP Amer Soc Clin Oncol C1 Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. Weill Cornell Med Coll, New York, NY USA. Columbia Univ, Med Ctr, New York, NY USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Baylor Coll Med, Houston, TX 77030 USA. Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA. NCI, Bethesda, MD 20892 USA. NCI, Canc Prevent Div, Rockville, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 MAY 20 PY 2014 VL 32 IS 15 SU S MA TPS1615 PG 1 WC Oncology SC Oncology GA CN7KL UT WOS:000358613202013 ER PT J AU Haluska, P Bernath, AM Ballman, KV Dueck, AC Linden, HM Goetz, MP Northfelt, DW Hou, XN Tenner, KS Tienchaiananda, P Flickinger, LM Chen, BY Chen, HX Lingle, WL Pellegrino, CM Sponzo, RW Reinholz, MM Perez, EA AF Haluska, Paul Bernath, Albert M. Ballman, Karla V. Dueck, Amylou C. Linden, Hannah M. Goetz, Matthew P. Northfelt, Donald W. Hou, Xiaonan Tenner, Kathleen S. Tienchaiananda, Piyawan Flickinger, Lynn M. Chen, Beiyun Chen, Helen X. Lingle, Wilma L. Pellegrino, Christine M. Sponzo, Robert W. Reinholz, Monica Madden Perez, Edith A. CA Alliance Clinical Trials Oncology TI Randomized phase II trial of capecitabine and lapatinib with or without cixutumumab in patients with HER2+breast cancer previously treated with trastuzumab and an anthracycline and/or a taxane: NCCTG N0733 (Alliance). SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT 50th Annual Meeting of the American-Society-of-Clinical-Oncology CY MAY 30-JUN 03, 2014 CL Chicago, IL SP Amer Soc Clin Oncol C1 Mayo Clin, Rochester, MN USA. Geisinger Hlth Syst, Danville, PA USA. Mayo Clin, Scottsdale, AZ USA. Univ Washington, Seattle, WA 98195 USA. Ramathibodi Hosp, Bangkok, Thailand. NCI, Canc Therapy Evaluat Program, Bethesda, MD 20892 USA. Montefiore Med Ctr, New York, NY USA. Glens Falls Hosp, Glens Falls, NY USA. Mayo Clin, Jacksonville, FL 32224 USA. NR 0 TC 0 Z9 0 U1 1 U2 2 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 MAY 20 PY 2014 VL 32 IS 15 SU S MA 632 PG 1 WC Oncology SC Oncology GA CN7KL UT WOS:000358613202405 ER PT J AU Han, TJ Lee, A Mister, D Miller, AH Torres, MA AF Han, Tatiana Jihae Lee, Anna Mister, Donna Miller, Andrew H. Torres, Mylin Ann TI The influence of childhood trauma on fatigue and depression in breast cancer patients during and after radiotherapy SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT 50th Annual Meeting of the American-Society-of-Clinical-Oncology CY MAY 30-JUN 03, 2014 CL Chicago, IL SP Amer Soc Clin Oncol C1 Emory Univ, Dept Radiat Oncol, Winship Canc Inst, Atlanta, GA 30322 USA. Mercer Univ, Sch Med, Macon, GA 31207 USA. Emory Univ, Sch Med, Atlanta, GA USA. Emory Univ, NSABP, Atlanta, GA 30322 USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X EI 1527-7755 J9 J CLIN ONCOL JI J. Clin. Oncol. PD MAY 20 PY 2014 VL 32 IS 15 SU S MA e20567 PG 1 WC Oncology SC Oncology GA CN7KL UT WOS:000358613201551 ER PT J AU Hanasoge, S Wang, XJ Chen, ZJ Mister, D Miller, AH Torres, MA AF Hanasoge, Sheela Wang, Xiaojing Chen, Zhengjia Mister, Donna Miller, Andrew H. Torres, Mylin Ann TI The influence of radiotherapy on sleep disturbances in breast cancer patients. SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT 50th Annual Meeting of the American-Society-of-Clinical-Oncology CY MAY 30-JUN 03, 2014 CL Chicago, IL SP Amer Soc Clin Oncol C1 Emory Univ, Winship Canc Inst, Dept Radiat Oncol, Atlanta, GA 30322 USA. Emory Univ, Winship Canc Inst, Dept Biostat & Bioinformat, Atlanta, GA 30322 USA. Emory Univ, Winship Canc Inst, Atlanta, GA 30322 USA. Emory Univ, Sch Med, Atlanta, GA USA. Emory Univ, Winship Canc Inst, NSABP, Atlanta, GA 30322 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 MAY 20 PY 2014 VL 32 IS 15 SU S MA 1092 PG 1 WC Oncology SC Oncology GA CN7KL UT WOS:000358613202513 ER PT J AU Hassan, R Alley, EW Kindler, HL Antonia, SJ Jahan, TM Jacobs-Small, M Hull, J McDougall, K Lemmens, E Murphy, A Grous, JJ Dubensky, T Brockstedt, DG AF Hassan, Raffit Alley, Evan W. Kindler, Hedy Lee Antonia, Scott Joseph Jahan, Thierry Marie Jacobs-Small, Mona Hull, Jennifer McDougall, Katherine Lemmens, Ed Murphy, Aimee Grous, John J. Dubensky, Thomas Brockstedt, Dirk G. TI Antimesothelin vaccine CRS-207 plus chemotherapy as front-line treatment for malignant pleural mesothelioma (MPM). SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT 50th Annual Meeting of the American-Society-of-Clinical-Oncology CY MAY 30-JUN 03, 2014 CL Chicago, IL SP Amer Soc Clin Oncol C1 NCI, NIH, Bethesda, MD 20892 USA. Univ Penn, Abramson Canc Ctr, Philadelphia, PA 19104 USA. Univ Chicago, Chicago, IL 60637 USA. Univ S Florida, Coll Med, H Lee Moffitt Canc Ctr & Res Inst, Tampa, FL 33612 USA. Univ Calif San Francisco, San Francisco, CA 94143 USA. Aduro BioTech Inc, Berkeley, CA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 MAY 20 PY 2014 VL 32 IS 15 SU S MA 7532 PG 1 WC Oncology SC Oncology GA CN7KL UT WOS:000358613203968 ER PT J AU Heery, CR Singh, H Marte, JL Madan, RA Coyne, GHO Farsaci, B Rodell, TC Palena, C Schlom, J Gulley, JL AF Heery, Christopher Ryan Singh, Harpreet Marte, Jennifer L. Madan, Ravi Amrit Coyne, Geraldine Helen O'Sullivan Farsaci, Benedetto Rodell, Timothy C. Palena, Claudia Schlom, Jeffrey Gulley, James L. TI NCI experience using yeast-brachyury vaccine (GI-6301) in patients (pt) with advanced chordonia. SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT 50th Annual Meeting of the American-Society-of-Clinical-Oncology CY MAY 30-JUN 03, 2014 CL Chicago, IL SP Amer Soc Clin Oncol C1 NCI, Tumor Immunol & Biol Lab, NIH, Bethesda, MD 20892 USA. NIH, Genitourinary Malignancies Branch, Bethesda, MD 20892 USA. NCI, NIH, Bethesda, MD 20892 USA. NCI, Genitourinary Malignancies Branch, NIH, Bethesda, MD 20892 USA. Ctr Canc Res, Tumor Immunol & Biol Lab, Bethesda, MD USA. Globelmmune Inc, Louisville, CO USA. NCI, Tumor Immunol & Biol Lab, Bethesda, MD 20892 USA. RI Gulley, James/K-4139-2016 OI Gulley, James/0000-0002-6569-2912 NR 0 TC 0 Z9 0 U1 0 U2 0 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 MAY 20 PY 2014 VL 32 IS 15 SU S MA 3081 PG 1 WC Oncology SC Oncology GA CN7KL UT WOS:000358613202972 ER PT J AU Heery, CR Coyne, GHO Madan, RA Schlom, J von Heydebreck, A Cuillerot, JM Sabzevari, H Gulley, JL AF Heery, Christopher Ryan Coyne, Geraldine Helen O'Sullivan Madan, Ravi Amrit Schlom, Jeffrey von Heydebreck, Anja Cuillerot, Jean-Marie Sabzevari, Helen Gulley, James L. TI Phase I open-label, multiple ascending dose trial of MSB0010718C, an anti-PD-L1 monoclonal antibody, in advanced solid malignancies. SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT 50th Annual Meeting of the American-Society-of-Clinical-Oncology CY MAY 30-JUN 03, 2014 CL Chicago, IL SP Amer Soc Clin Oncol C1 NCI, Tumor Immunol & Biol Lab, NIH, Bethesda, MD 20892 USA. NCI, Genitourinary Malignancies Branch, NIH, Bethesda, MD 20892 USA. Merck KGaA, Darmstadt, Germany. EMD Serono, Billerica, MA USA. EMD Serono, Rockland, MA USA. RI Gulley, James/K-4139-2016 OI Gulley, James/0000-0002-6569-2912 NR 0 TC 1 Z9 1 U1 0 U2 2 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 MAY 20 PY 2014 VL 32 IS 15 SU S MA 3064 PG 1 WC Oncology SC Oncology GA CN7KL UT WOS:000358613202955 ER PT J AU Hershman, DL Unger, JM Crew, KD Dakhil, SR Awad, D Greenlee, H Minasian, LM Hansen, L Lew, D Gralow, J Wade, JL Meyskens, FL Moinpour, C AF Hershman, Dawn L. Unger, Joseph M. Crew, Katherine D. Dakhil, Shaker R. Awad, Danielle Greenlee, Heather Minasian, Lori M. Hansen, Lisa Lew, Danika Gralow, Julie Wade, James Lloyd Meyskens, Frank L. Moinpour, Carol TI Omega-3 fatty acids for aromatase inhibitor-induced musculoskeletal symptoms in women with early-stage breast cancer (SWOG S0927). SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT 50th Annual Meeting of the American-Society-of-Clinical-Oncology CY MAY 30-JUN 03, 2014 CL Chicago, IL SP Amer Soc Clin Oncol C1 Columbia Univ, Med Ctr, New York, NY USA. SWOG Stat Ctr, Seattle, WA USA. Wichita Community Clin Oncol Program, Wichita, KS USA. NCI, Bethesda, MD 20892 USA. Legacy Good Samaritan Hosp, Portland, OR USA. Southwest Oncol Grp, Ctr Stat, Seattle, WA USA. Seattle Canc Care Alliance, Seattle, WA USA. Canc Care Ctr Decatur, Decatur, IL USA. Chao Family Comprehens Canc Ctr, Orange, CA USA. Fred Hutchinson Canc Res Ctr, Seattle, WA 98104 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 MAY 20 PY 2014 VL 32 IS 15 SU S MA 9532 PG 1 WC Oncology SC Oncology GA CN7KL UT WOS:000358613204416 ER PT J AU Heske, C Yeung, C Cao, L Wan, XL Helman, LJ AF Heske, Christine Yeung, Choh Cao, Liang Wan, Xiaolin Helman, Lee J. TI Identification of PDGFR-beta activation as a potential bypass resistance pathway in a rhabdomyosarcoma (RMS) model of acquired resistance to IGF-I receptor blockade. SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT 50th Annual Meeting of the American-Society-of-Clinical-Oncology CY MAY 30-JUN 03, 2014 CL Chicago, IL SP Amer Soc Clin Oncol C1 NCI, NIH, Bethesda, MD 20892 USA. NCI, Pediat Oncol Branch, Bethesda, MD 20892 USA. NCI, Pediat Oncol, CCR, NIH, Bethesda, MD 20892 USA. NCI, Ctr Canc Res, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 MAY 20 PY 2014 VL 32 IS 15 SU S MA 10046 PG 1 WC Oncology SC Oncology GA CN7KL UT WOS:000358613204585 ER PT J AU Hinrichs, CS Stevanovic, S Draper, L Somerville, R Wunderlich, J Restifo, NP Sherry, R Giao, PQ Kammula, US Yang, JC Rosenberg, SA AF Hinrichs, Christian S. Stevanovic, Sanja Draper, Lindsey Somerville, Robert Wunderlich, John Restifo, Nicholas P. Sherry, Richard Giao, Phan Q. Kammula, Udal S. Yang, James C. Rosenberg, Steven A. TI HPV-targeted tumor-infiltrating lymphocytes for cervical cancer. SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT 50th Annual Meeting of the American-Society-of-Clinical-Oncology CY MAY 30-JUN 03, 2014 CL Chicago, IL SP Amer Soc Clin Oncol C1 NCI, Bethesda, MD 20892 USA. NCI, Surg Branch, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X EI 1527-7755 J9 J CLIN ONCOL JI J. Clin. Oncol. PD MAY 20 PY 2014 VL 32 IS 15 SU S MA LBA3008 PG 1 WC Oncology SC Oncology GA CN7KL UT WOS:000358613201958 ER PT J AU Hoffman-Censits, JH Vaughn, DJ Lin, JQ Keefe, SM Haas, NB Kelly, WK Hyslop, T McGulre, M Robinson, J Khadar, K Nanda, S Kennedy, B Apolo, AB AF Hoffman-Censits, Jean H. Vaughn, David J. Lin, Jianqing Keefe, Stephen Michael Haas, Naomi B. Kelly, William Kevin Hyslop, Terry McGulre, Monica Robinson, Janelle Khadar, Kahle Nanda, Swati Kennedy, Brooke Apolo, Andrea Borghese TI A phase II study of cabazitaxel in patients with urothelial carcinoma who have disease progression following platinum based chemotherapy. SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT 50th Annual Meeting of the American-Society-of-Clinical-Oncology CY MAY 30-JUN 03, 2014 CL Chicago, IL SP Amer Soc Clin Oncol C1 Thomas Jefferson Univ, Kimmel Canc Ctr, Philadelphia, PA 19107 USA. Univ Penn, Abramson Canc Ctr, Philadelphia, PA 19104 USA. Duke Canc Inst, Dept Biostat & Bioinformat, Durham, NC USA. NCI, Med Oncol Branch, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 MAY 20 PY 2014 VL 32 IS 15 SU S MA e15519 PG 1 WC Oncology SC Oncology GA CN7KL UT WOS:000358613200667 ER PT J AU Hong, TS Szymonifka, J Yothers, G Blaszkowsky, LS Russo, AL Wo, JYL Mamon, HJ Kwak, EL Zhu, AX Allen, JN Clark, JW Ryan, DP AF Hong, Theodore S. Szymonifka, Jackie Yothers, Greg Blaszkowsky, Lawrence Scott Russo, Andrea Lyn Wo, Jennifer Yon-Li Mamon, Harvey J. Kwak, Eunice Lee Zhu, Andrew X. Allen, Jill N. Clark, Jeffrey W. Ryan, David P. TI Validation of the NSABP neoadjuvant rectal score (NAR) in a prospective phase II study evaluating an experimental regimen and a standard chemoradiation cohort with molecular genotyping. SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT 50th Annual Meeting of the American-Society-of-Clinical-Oncology CY MAY 30-JUN 03, 2014 CL Chicago, IL SP Amer Soc Clin Oncol C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. Massachusetts Gen Hosp, Biostat, Boston, MA 02114 USA. Natl Surg Adjuvant Breast & Bowel Project, Biostat Ctr, Pittsburgh, PA USA. Univ Pittsburgh, Grad Sch Publ Hlth, Dept Biostat, Pittsburgh, PA 15261 USA. Massachusetts Gen Hosp, Ctr Canc, Boston, MA USA. Harvard Radiat Oncol Program, Boston, MA USA. Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Massachusetts Gen Hosp, Div Hematol & Oncol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 MAY 20 PY 2014 VL 32 IS 15 SU S MA 3599 PG 1 WC Oncology SC Oncology GA CN7KL UT WOS:000358613203115 ER PT J AU Hubbard, JM Kim, GP Bored, MJ Qin, R Lensing, J Wright, JJ Erlichman, C Grothey, A AF Hubbard, Joleen Marie Kim, George P. Bored, Mitesh J. Qin, Rui Lensing, Janet Wright, John Joseph Erlichman, Charles Grothey, Axel TI Phase I trial of FOLFIRI in combination with sorafenib and bevacizumab in patients with advanced gastrointestinal malignancies. SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT 50th Annual Meeting of the American-Society-of-Clinical-Oncology CY MAY 30-JUN 03, 2014 CL Chicago, IL SP Amer Soc Clin Oncol C1 Mayo Clin, Rochester, MN USA. Mayo Clin, Jacksonville, FL 32224 USA. Mayo Clin, Scottsdale, AZ USA. Mayo Clin, Alliance Stat & Data Ctr, Rochester, MN USA. NCI, Rockville, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 MAY 20 PY 2014 VL 32 IS 15 SU S MA 2539 PG 1 WC Oncology SC Oncology GA CN7KL UT WOS:000358613202804 ER PT J AU Jasielec, J Kimball, AS Cohen, KS Kline, JP Rapoport, A Petrich, AM Nabhan, C Thomas, S Doyle, LA Stadler, WM Karrison, T Smith, SM AF Jasielec, Jagoda Kimball, Amy Sarah Cohen, Kenneth Stuart Kline, Justin Paul Rapoport, Aaron Petrich, Adam Matthew Nabhan, Chadi Thomas, Sachdev Doyle, Laurence A. Stadler, Walter Michael Karrison, Theodore Smith, Sonali M. TI Temsirolimus (TEM) and lenalidomide (LEN) in relapsed/refractory Hodgkin lymphoma including in patients with prior exposure to brentuximab vedotin (BV). SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT 50th Annual Meeting of the American-Society-of-Clinical-Oncology CY MAY 30-JUN 03, 2014 CL Chicago, IL SP Amer Soc Clin Oncol C1 Univ Chicago, Chicago, IL 60637 USA. Univ Maryland, Baltimore, MD 21201 USA. Northwestern Univ, Chicago, IL 60611 USA. Illinois Canc Ctr, Peoria, IL USA. NCI, Rockville, MD USA. NR 0 TC 1 Z9 1 U1 0 U2 0 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 MAY 20 PY 2014 VL 32 IS 15 SU S MA 8567 PG 1 WC Oncology SC Oncology GA CN7KL UT WOS:000358613204246 ER PT J AU Jawed, I Wilkerson, J Pichun, MEB Duffy, AG Fojo, AT AF Jawed, Irfan Wilkerson, Julia Pichun, Mauricio Emmanuel Burotto Duffy, Austin G. Fojo, Antonio Tito TI Effect of chemotherapy on the progress in colorectal cancer survival in the past two decades. SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT 50th Annual Meeting of the American-Society-of-Clinical-Oncology CY MAY 30-JUN 03, 2014 CL Chicago, IL SP Amer Soc Clin Oncol C1 Lawrence Mem Hosp Oncol Ctr, Lawrence, KS USA. NCI, Med Oncol Branch, Bethesda, MD 20892 USA. NCI, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X EI 1527-7755 J9 J CLIN ONCOL JI J. Clin. Oncol. PD MAY 20 PY 2014 VL 32 IS 15 SU S MA 3642 PG 1 WC Oncology SC Oncology GA CN7KL UT WOS:000358613203158 ER PT J AU Jones, JA Andritsos, LA Lucas, DM Lozanski, G Hutchinson, T Sexton, JL Harris, PJ Grever, MR AF Jones, Jeffrey Alan Andritsos, Leslie A. Lucas, David M. Lozanski, Gerard Hutchinson, Terri Sexton, Jennifer L. Harris, Pamela Jo Grever, Michael R. TI Preliminary safety and efficacy of the Bruton's tyrosine kinase (BTK) inhibitor ibrutinib (IBR) in patients (pts) with hairy cell leukemia (HCL). SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT 50th Annual Meeting of the American-Society-of-Clinical-Oncology CY MAY 30-JUN 03, 2014 CL Chicago, IL SP Amer Soc Clin Oncol C1 Ohio State Univ, Columbus, OH 43210 USA. Ohio State Univ, Ctr Comprehens Canc, Columbus, OH 43210 USA. NCI, Bethesda, MD 20892 USA. NR 0 TC 4 Z9 4 U1 0 U2 0 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 MAY 20 PY 2014 VL 32 IS 15 SU S MA 7063 PG 1 WC Oncology SC Oncology GA CN7KL UT WOS:000358613203880 ER PT J AU Joshi, J Mounier, N Xue, XN Wang, D Ribera, JM Wyen, C Dunleavy, K Little, RF Wilson, WH Noy, A Sparano, JA Barta, SK AF Joshi, Jitesh Mounier, Nicolas Xue, Xiaonan Wang, Dan Ribera, Josep-Maria Wyen, Christoph Dunleavy, Kieron Little, Richard F. Wilson, Wyndham Hopkins Noy, Ariela Sparano, Joseph A. Barta, Stefan K. TI CNS involvement in patients with AIDS-related lymphomas. SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT 50th Annual Meeting of the American-Society-of-Clinical-Oncology CY MAY 30-JUN 03, 2014 CL Chicago, IL SP Amer Soc Clin Oncol C1 Montefiore Med Ctr, Albert Einstein Coll Med, Bronx, NY 10467 USA. Ctr Hosp Univ Archet, Nice, France. Albert Einstein Coll Med, Bronx, NY 10467 USA. Hosp Badalona Germans Trias & Pujol, Barcelona, Spain. Univ Hosp Cologne, Cologne, Germany. NCI, Metab Branch, NIH, Bethesda, MD 20892 USA. NCI, Bethesda, MD 20892 USA. Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. Montefiore Med Ctr, Bronx, NY 10467 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 MAY 20 PY 2014 VL 32 IS 15 SU S MA 8570 PG 1 WC Oncology SC Oncology GA CN7KL UT WOS:000358613204249 ER PT J AU Karzal, F Shah, AA Ojemuyiwa, MA Madan, RA Apolo, AB Dawson, NA Arlen, PM Theoret, MR Wright, JJ Chen, C Trepel, JB Couvillon, A Chun, G Harold, N Steinberg, SM Price, DK Gulley, JL Figg, WD Dahut, WL AF Karzal, Fatima Shah, Avani Atul Ojemuyiwa, Michelle A. Madan, Ravi Amrit Apolo, Andrea Borghese Dawson, Nancy Ann Arlen, Phillp M. Theoret, Marc Robert Wright, John Joseph Chen, Clara Trepel, Jane B. Couvillon, Anna Chun, Guinevere Harold, Nancy Steinberg, Seth M. Price, Douglas K. Gulley, James L. Figg, William Douglas Dahut, William L. TI A safety study of cabozantinib (C) plus docetaxel (D) and prednisone (P) in metastatic castrate-resistant prostate cancer (mCRPC). SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT 50th Annual Meeting of the American-Society-of-Clinical-Oncology CY MAY 30-JUN 03, 2014 CL Chicago, IL SP Amer Soc Clin Oncol C1 NCI, Bethesda, MD 20892 USA. NCI, NIH, Bethesda, MD 20892 USA. Walter Reed Natl Mil Med Ctr, Bethesda, MD USA. Georgetown Lombardi Comprehens Canc Ctr, Washington, DC USA. NCI, Med Oncol Branch, NIH, Bethesda, MD 20892 USA. NCI, Clin Ctr, NIH, Bethesda, MD 20892 USA. NCI, Rockville, MD USA. NIH, Dept Nucl Med, Ctr Clin, Bethesda, MD 20892 USA. NCI, Dev Therapeut Branch, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. NCI, Biostat & Data Management Sect, Ctr Canc Res, Bethesda, MD 20892 USA. NCI, Mol Pharmacol Sect, NIH, Bethesda, MD 20892 USA. RI Gulley, James/K-4139-2016; Figg Sr, William/M-2411-2016 OI Gulley, James/0000-0002-6569-2912; NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X EI 1527-7755 J9 J CLIN ONCOL JI J. Clin. Oncol. PD MAY 20 PY 2014 VL 32 IS 15 SU S MA 5072 PG 1 WC Oncology SC Oncology GA CN7KL UT WOS:000358613203464 ER PT J AU Kaveney, AD Mehnert, JM Tan, AR Aisner, J Moss, RA Gibbon, D Adams, S Fischer, J Scott, P Gable, C Doyle, A DiPaola, RS Stein, MN AF Kaveney, Amanda D. Mehnert, Janice M. Tan, Antoinette R. Aisner, Joseph Moss, Rebecca Anne Gibbon, Darlene Adams, Shari Fischer, Jane Scott, Pamela Gable, Christian Doyle, Austin DiPaola, Robert S. Stein, Mark N. TI A phase I trial of MK-2206 and hydroxychloroquine(HCQ) in solid tumors, melanoma, renal, and prostate cancer to examine the role of antophagy in tomorigenesis SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT 50th Annual Meeting of the American-Society-of-Clinical-Oncology CY MAY 30-JUN 03, 2014 CL Chicago, IL SP Amer Soc Clin Oncol C1 New Jersey Robert Wood Johnson Hosp, Inst Canc, New Brunswick, NJ USA. Rutgers Canc Inst New Jersey, New Brunswick, NJ USA. NSABP, New Brunswick, NJ USA. Rutgers Robert Wood Johnson Med Sch, Rutgers Canc Inst New Jersey, New Brunswick, NJ USA. Canc Inst New Jersey, New Brunswick, NJ USA. Rutgers Canc Inst New Jersey, New Brunswick, NJ USA. NCI, Rockville, MD USA. Rutgers Biomed & Hlth Sci, New Brunswick, NJ USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X EI 1527-7755 J9 J CLIN ONCOL JI J. Clin. Oncol. PD MAY 20 PY 2014 VL 32 IS 15 SU S MA TPS2640 PG 1 WC Oncology SC Oncology GA CN7KL UT WOS:000358613202041 ER PT J AU Keat, NJ Law, K McConnell, A Calvo, FM Negrouk, A Lacombe, DA Welch, J Trimble, EL Gross, T De Schaetzen, G Brachot, JM Pauporta, I O'Riordan, M Seymour, MT AF Keat, Nicola Jane Law, Kate McConnell, Andrea Calvo, Fabian M. Negrouk, Anastasia Lacombe, Denis A. Welch, Jack Trimble, Edward Lloyd Gross, Thomas De Schaetzen, Gaetan Brachot, Jeanne-Mane Pauporta, Iris O'Riordan, Maura Seymour, Matthew T. TI The international rare cancers initiative. SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT 50th Annual Meeting of the American-Society-of-Clinical-Oncology CY MAY 30-JUN 03, 2014 CL Chicago, IL SP Amer Soc Clin Oncol C1 Canc Res UK, London, England. Univ Paris 07, Hop St Louis, APHP, Lab Pharmacol,INSERM,IUH, Paris, France. European Org Res Treatment Canc, Brussels, Belgium. NCI, Bethesda, MD 20892 USA. NCI, Ctr Global Hlth, NIH, DHHS, Rockville, MD USA. EORTC Headquarters, Brussels, Belgium. Natl Canc Inst, Boulogne, France. NCI Ctr Global Hlth, Brussels, Belgium. Natl Inst Hlth, Res Canc Res Network, Leeds, W Yorkshire, England. NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X EI 1527-7755 J9 J CLIN ONCOL JI J. Clin. Oncol. PD MAY 20 PY 2014 VL 32 IS 15 SU S MA e17504 PG 1 WC Oncology SC Oncology GA CN7KL UT WOS:000358613200965 ER PT J AU Kehl, KL Landrum, MB Arora, NK Ganz, PA van Ryn, M Mack, JW Keating, NL AF Kehl, Kenneth L. Landrum, Mary Beth Arora, Neeraj K. Ganz, Patricia A. van Ryn, Michelle Mack, Jennifer W. Keating, Nancy Lynn TI Decisions about cancer treatment: Matching of actual to preferred roles and patient ratings of care SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT 50th Annual Meeting of the American-Society-of-Clinical-Oncology CY MAY 30-JUN 03, 2014 CL Chicago, IL SP Amer Soc Clin Oncol C1 Brigham & Womens Hosp, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Hlth Care Policy, Boston, MA 02115 USA. NCI, NIH, Bethesda, MD 20892 USA. Univ Calif Los Angeles, Los Angeles, CA USA. Univ Minnesota, Minneapolis, MN USA. Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 MAY 20 PY 2014 VL 32 IS 15 SU S MA 6533 PG 1 WC Oncology SC Oncology GA CN7KL UT WOS:000358613203719 ER PT J AU Kehl, KL Arora, NK Schrag, D Ayanian, J Clauser, S Klabunde, CN Kahn, KL Fletcher, RH Keating, NL AF Kehl, Kenneth L. Arora, Neeraj K. Schrag, Deborah Ayanian, John Clauser, Steven Klabunde, Carrie N. Kahn, Katherine Leslie Fletcher, Robert H. Keating, Nancy Lynn TI Discussions about clinical trials among patients with lung and colorectal cancer SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT 50th Annual Meeting of the American-Society-of-Clinical-Oncology CY MAY 30-JUN 03, 2014 CL Chicago, IL SP Amer Soc Clin Oncol C1 Brigham & Womens Hosp, Boston, MA 02115 USA. NCI, NIH, Bethesda, MD 20892 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Univ Michigan, Ann Arbor, MI 48109 USA. Univ Calif Los Angeles, David Geffen Sch Med, Los Angeles, CA 90095 USA. Harvard Univ, Sch Med, Boston, MA USA. Harvard Univ, Sch Med, Dept Hlth Care Policy, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 MAY 20 PY 2014 VL 32 IS 15 SU S MA 6509 PG 1 WC Oncology SC Oncology GA CN7KL UT WOS:000358613203695 ER PT J AU Khanna, P Hollingshead, MG Parchment, RE Kinders, RJ Tomaszewskl, JE Doroshow, JH Srivastava, AK AF Khanna, Payal Hollingshead, Melinda G. Parchment, Ralph E. Kinders, Robert J. Tomaszewskl, Joseph E. Doroshow, James H. Srivastava, Apurva K. TI Pharmacodynamic assay for evaluation of first-in-class pyrovate kinase-M2 activators in tumors SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT 50th Annual Meeting of the American-Society-of-Clinical-Oncology CY MAY 30-JUN 03, 2014 CL Chicago, IL SP Amer Soc Clin Oncol C1 Leidos Biomed Res Inc, Fredrick Natl Lab Canc Res, Frederick, MD USA. NCI, Frederick, MD 21701 USA. Frederick Natl Lab Canc Res, Ledios Biomed, Frederick, MD USA. NCI, Div Canc Treatment & Diag, Bethesda, MD 20892 USA. NCI, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 MAY 20 PY 2014 VL 32 IS 15 SU S MA 2551 PG 1 WC Oncology SC Oncology GA CN7KL UT WOS:000358613202816 ER PT J AU Kim, A Reinke, DK Cichowski, K Perentesis, JP Wolters, P Martin, S Dombl, E Steinberg, SM Widemann, BC AF Kim, AeRang Reinke, Denise K. Cichowski, Karen Perentesis, John Peter Wolters, Pamela Martin, Stacl Dombl, Eva Steinberg, Seth M. Widemann, Brigitte C. TI SARC023: Phase I/II trial of ganetespib in combination with sirolimus for refractory sarcomas and malignant peripheral nerve sheath tumors (MPNST). SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT 50th Annual Meeting of the American-Society-of-Clinical-Oncology CY MAY 30-JUN 03, 2014 CL Chicago, IL SP Amer Soc Clin Oncol C1 Childrens Natl Med Ctr, Ctr Canc & Blood Disorders, Washington, DC 20010 USA. Sarcoma Alliance Res Collaborat, Ann Arbor, MI USA. Brigham & Womens Hosp, Boston, MA 02115 USA. Cincinnati Childrens Hosp Med Ctr, Cincinnati, OH 45229 USA. NCI, Bethesda, MD 20892 USA. NCI, Biostat & Data Management Sect, Ctr Canc Res, Bethesda, MD 20892 USA. NCI, Pediat Oncol Branch, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 MAY 20 PY 2014 VL 32 IS 15 SU S MA TPS10603 PG 1 WC Oncology SC Oncology GA CN7KL UT WOS:000358613202268 ER PT J AU Konstantinopoulos, P Makker, V Barry, WT Liu, J Horowitz, NS Birrer, MJ Doyle, LA Berlin, ST Whalen, C Van Hummelen, P Coleman, RL Aghajanian, C Mills, GB Matulonis, U Westin, SN Myers, AP AF Konstantinopoulos, Panagiotis Makker, Vicky Barry, William Thomas Liu, Joyce Horowitz, Neil S. Birrer, Michael J. Doyle, L. Austin Berlin, Suzanne T. Whalen, Christin Van Hummelen, Paul Coleman, Robert L. Aghajanian, Carol Mills, Gordon B. Matulonis, Ursula Westin, Shannon Neville Myers, Andrea P. TI Phase II, single stage, cohort expansion study of MK-2206 in recurrent endometrial serous cancer. SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT 50th Annual Meeting of the American-Society-of-Clinical-Oncology CY MAY 30-JUN 03, 2014 CL Chicago, IL SP Amer Soc Clin Oncol C1 Dana Farber Canc Inst, Boston, MA 02115 USA. Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. Brigham & Womens Hosp, Boston, MA 02115 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. NCI, Rockville, MD USA. Dana Farber Canc Inst, Ctr Canc Genome Discovery, Boston, MA 02115 USA. Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA. Novartis Inst BioMed Res, Cambridge, MA USA. NR 0 TC 2 Z9 2 U1 0 U2 0 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 MAY 20 PY 2014 VL 32 IS 15 SU S MA 5515 PG 1 WC Oncology SC Oncology GA CN7KL UT WOS:000358613203500 ER PT J AU Kummar, S Williams, M Lih, CJ Chen, AP Rubinstein, L Antony, R Polley, E Zhao, YD Conley, BA Simon, R Doroshow, JH AF Kummar, Shivaani Williams, Mickey Lih, Chih-Jian Chen, Alice P. Rubinstein, Larry Antony, Ramya Polley, Eric Zhao, Yingdong Conley, Barbara A. Simon, Richard Doroshow, James H. TI NCI mpact: National Cancer Institute molecular profiling-based assignment of cancer therapy. SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT 50th Annual Meeting of the American-Society-of-Clinical-Oncology CY MAY 30-JUN 03, 2014 CL Chicago, IL SP Amer Soc Clin Oncol C1 NCI, Bethesda, MD 20892 USA. Leidos Biomed Res Inc, Frederick, MD USA. Div Canc Treatment & Diag, Bethesda, MD USA. NCI, Div Canc Treatment & Diag, Rockville, MD USA. NIH, Bethesda, MD 20892 USA. NCI, NIH, Bethesda, MD 20892 USA. NR 0 TC 1 Z9 1 U1 0 U2 0 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 MAY 20 PY 2014 VL 32 IS 15 SU S MA TPS2642 PG 1 WC Oncology SC Oncology GA CN7KL UT WOS:000358613202043 ER PT J AU Lai, C Cole, D Shovlin, M Widemann, BC Dunleavy, K Wilson, WH AF Lai, Catherine Cole, Diane Shovlin, Margaret Widemann, Brigitte C. Dunleavy, Kieron Wilson, Wyndham Hopkins TI Pharmacokinetics and tolerability of doxorubicin in newly diagnosed lymphoma patients with hepatic impairment. SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT 50th Annual Meeting of the American-Society-of-Clinical-Oncology CY MAY 30-JUN 03, 2014 CL Chicago, IL SP Amer Soc Clin Oncol C1 NCI, NIH, Bethesda, MD 20892 USA. Pediat Oncol Branch, Bethesda, MD USA. NCI, Metab Branch, NIH, Bethesda, MD 20892 USA. NCI, Pediat Oncol Branch, NIH, Bethesda, MD 20892 USA. NCI, Metab Branch, NIH, Bethesda, MD 20892 USA. NCI, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X EI 1527-7755 J9 J CLIN ONCOL JI J. Clin. Oncol. PD MAY 20 PY 2014 VL 32 IS 15 SU S MA 8547 PG 1 WC Oncology SC Oncology GA CN7KL UT WOS:000358613204226 ER PT J AU Lam, CJK Curtis, RE Dores, G Engels, EA Caporaso, N Poillack, A Young, HA Levine, PH Elmi, AF Fraumeni, JF Tucker, MA Morton, LM AF Lam, Clara J. K. Curtis, Rochelle E. Dores, Graca Engels, Eric A. Caporaso, Neil Poillack, Aaron Young, Heather A. Levine, Paul H. Elmi, Angelo F. Fraumeni, Joseph F. Tucker, Margaret A. Morton, Lindsay M. TI Risk factors for melanoma among survivors of non-Hodgkin lymphoma in the US elderly population. SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT 50th Annual Meeting of the American-Society-of-Clinical-Oncology CY MAY 30-JUN 03, 2014 CL Chicago, IL SP Amer Soc Clin Oncol C1 NCI, Rockville, MD USA. NCI, Div Canc Epidemiol & Genet, NIH, DHHS, Bethesda, MD 20892 USA. Dept Vet Affairs Med Ctr, Oklahoma City, OK USA. NCI, Div Canc Epidemiol & Genet, Rockville, MD USA. NCI, Bethesda, MD 20892 USA. Hadassah Univ Hosp, IL-91120 Jerusalem, Israel. Hebrew Univ Jerusalem, Sch Med, IL-91010 Jerusalem, Israel. George Washington Univ, Washington, DC USA. George Washington Univ, Dept Epidemiol & Biostat, Washington, DC USA. George Washington Univ, Sch Publ Hlth & Hlth Sci, Washington, DC USA. NCI, NIH, Rockville, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 MAY 20 PY 2014 VL 32 IS 15 SU S MA 1533 PG 1 WC Oncology SC Oncology GA CN7KL UT WOS:000358613202585 ER PT J AU Land, SR Walcott, FL Liu, Q Wickerham, DL Costantino, JP Ganz, PA AF Land, Stephanie R. Walcott, Farzana L. Liu, Qing Wickerham, Donald Lawrence Costantino, Joseph P. Ganz, Patricia A. TI Patient-reported outcomes and behavioral risk factors as predictors of chemoprevention adherence among women in the National Surgical Adjuvant Breast and Bowel Program (NSABP) Breast Cancer Prevention P-1 trial. SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT 50th Annual Meeting of the American-Society-of-Clinical-Oncology CY MAY 30-JUN 03, 2014 CL Chicago, IL SP Amer Soc Clin Oncol C1 NCI, Rockville, MD USA. Univ Pittsburgh, Grad Sch Publ Hlth, Pittsburgh, PA USA. Natl Surg Adjuvant Breast & Bowel Project, Pittsburgh, PA USA. Allegheny Gen Hosp, Pittsburgh, PA 15212 USA. Univ Pittsburgh, Grad Sch Publ Hlth, Ctr Biostat, Natl Surg Adjuvant Breast & Bowel Project, Pittsburgh, PA USA. Univ Pittsburgh, Grad Sch Publ Hlth, Dept Biostat, Pittsburgh, PA 15261 USA. Univ Calif Los Angeles, Los Angeles Sch Med & Publ Hlth, Los Angeles, CA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 MAY 20 PY 2014 VL 32 IS 15 SU S MA 1512 PG 1 WC Oncology SC Oncology GA CN7KL UT WOS:000358613202564 ER PT J AU Land, SR Toll, B Warren, GW Brandon, TH Mitchell, SA Dresler, CM Gritz, ER Schnoll, R Sarna, L Moinpour, C Ostroff, JS Khuri, FR Buckner, JC Cummings, KM Herbst, RS Shields, PG Duffy, S Rigotti, N Prindiville, SA Abrams, JS AF Land, Stephanie R. Toll, Benjamin Warren, Graham Walter Brandon, Thomas H. Mitchell, Sandra A. Dresler, Carolyn M. Gritz, Ellen R. Schnoll, Robert Sarna, Linda Moinpour, Carol Ostroff, Jamie S. Khuri, Fadio Raja Buckner, Jan C. Cummings, Kenneth Michael Herbst, Roy S. Shields, Peter G. Duffy, Sonia Rigotti, Nancy Prindiville, Sheila Ann Abrams, Jeffrey S. CA Natl Canc Inst Amer Assoc Canc Res TI Standardizing measurement of tobacco use in cancer clinical trials SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT 50th Annual Meeting of the American-Society-of-Clinical-Oncology CY MAY 30-JUN 03, 2014 CL Chicago, IL SP Amer Soc Clin Oncol C1 NCI, Rockville, MD USA. Yale Univ, New Haven, CT USA. Med Univ S Carolina, Charleston, SC 29425 USA. Univ S Florida, H Lee Moffitt Canc Ctr, Tampa, FL 33682 USA. Arkansas Dept Hlth, Little Rock, AR 72205 USA. Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA. Univ Penn, Philadelphia, PA 19104 USA. Univ Calif Los Angeles, Los Angeles, CA USA. Fred Hutchinson Canc Res Ctr, Seattle, WA 98104 USA. Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. Emory Univ, Winship Canc Inst, Atlanta, GA 30322 USA. Mayo Clin, Rochester, MN USA. Yale Univ, Sch Med, Dept Med Oncol, New Haven, CT USA. Ohio State Univ, Wexner Med Ctr, Columbus, OH 43210 USA. Univ Michigan, Ann Arbor, MI 48109 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. NCI, Coordinating Ctr Clin Trails, Bethesda, MD 20892 USA. NCI, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 MAY 20 PY 2014 VL 32 IS 15 SU S MA e17658 PG 1 WC Oncology SC Oncology GA CN7KL UT WOS:000358613201112 ER PT J AU Lee, JM Annunziata, CM Hays, JL Choyke, PL Cao, L Yu, MS Azad, NS Houston, ND Minasian, LM Gordon, N Chen, HX Wright, JJ Kohn, EC AF Lee, Jung-Min Annunziata, Christina M. Hays, John L. Choyke, Peter L. Cao, Liang Yu, Minshu Azad, Nilofer Saba Houston, Nicole D. Minasian, Lori M. Gordon, Nicolas Chen, Helen X. Wright, John Joseph Kohn, Elise C. TI A phase II study of intermittent sorafenib with bevacizumab (B) in B-naive and prior B-exposed epithelial ovarian cancer (EOC) patients. SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT 50th Annual Meeting of the American-Society-of-Clinical-Oncology CY MAY 30-JUN 03, 2014 CL Chicago, IL SP Amer Soc Clin Oncol C1 NCI, NIH, Bethesda, MD 20892 USA. NCI, Mol Signaling Sect, Med Oncol Branch, NIH, Bethesda, MD 20892 USA. NCI, Oncol Branch, Ctr Canc Res, Bethesda, MD 20892 USA. Johns Hopkins Univ, Sch Med, Baltimore, MD USA. Sidney Kimmel Comprehens Canc Ctr, Baltimore, MD USA. NCI, Bethesda, MD 20892 USA. NCI, Canc Therapy Evaluat Program, Bethesda, MD 20892 USA. NCI, Rockville, MD USA. RI Annunziata, Christina/L-3219-2016 OI Annunziata, Christina/0000-0003-2033-6532 NR 0 TC 2 Z9 2 U1 1 U2 1 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X EI 1527-7755 J9 J CLIN ONCOL JI J. Clin. Oncol. PD MAY 20 PY 2014 VL 32 IS 15 SU S MA 5553 PG 1 WC Oncology SC Oncology GA CN7KL UT WOS:000358613203537 ER PT J AU Lee, JM Liu, J Choyke, PL Elbuluk, O Turkbey, IB Trepei, JB Lee, MJ Cao, L Houston, ND Gordon, N Figg, WD Barry, WT Matulonis, U Birrer, MJ Ivy, P Kohn, EC AF Lee, Jung-min Liu, Joyce Choyke, Peter L. Elbuluk, Osama Turkbey, Ismail B. Trepei, Jane B. Lee, Min-Jung Cao, Liang Houston, Nicole D. Gordon, Nicolas Figg, William Douglas Barry, William Thomas Matulonis, Ursula Birrer, Michael J. Ivy, Percy Kohn, Elise C. TI Biomarker correlates from the randomized phase 2 trial of the PARP inhibitor olaparib (O) with or without the antiangiogenic TKI cediranib (C) in recurrent platinum-sensitive ovarian cancer (NCT01116648). SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT 50th Annual Meeting of the American-Society-of-Clinical-Oncology CY MAY 30-JUN 03, 2014 CL Chicago, IL SP Amer Soc Clin Oncol C1 NCI, NIH, Bethesda, MD 20892 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. NCI, Bethesda, MD 20892 USA. NCI, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. NCI, Dev Therapeut Branch, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. NIH, Bethesda, MD 20892 USA. NIH, Med Oncol Branch, Ctr Canc Res, Bethesda, MD 20892 USA. NCI, Mol Pharmacol Sect, NIH, Bethesda, MD 20892 USA. Duke Univ, Med Ctr, Durham, NC USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Massachusetts Gen Hosp, Boston, MA 02115 USA. RI Figg Sr, William/M-2411-2016 NR 0 TC 0 Z9 0 U1 1 U2 1 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X EI 1527-7755 J9 J CLIN ONCOL JI J. Clin. Oncol. PD MAY 20 PY 2014 VL 32 IS 15 SU S MA 5535 PG 1 WC Oncology SC Oncology GA CN7KL UT WOS:000358613203519 ER PT J AU Lheureux, S Ledermann, JA Kaye, SB Gourley, C Friedlander, M Bowtell, D De Greve, J deFazio, A Shapira-Frommer, R De Bono, JS Audeh, MW Kohn, EC Alsop, K Scott, CL Matulonis, U Kaufman, B Burger, B Robertson, JD Ho, T Oza, AM AF Lheureux, Stephanie Ledermann, Jonathan A. Kaye, Stanley B. Gourley, Charlie Friedlander, Michael Bowtell, David De Greve, Jacques deFazio, Anna Shapira-Frommer, Ronnie De Bono, Johann Sebastian Audeh, M. William Kohn, Elise C. Alsop, Kathryn Scott, Clare L. Matulonis, Ursula Kaufman, Bella Burger, Brent Robertson, Jane D. Ho, Tony Oza, Amit M. TI Characterization of ovarian cancer long-term responders on olaparib. SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT 50th Annual Meeting of the American-Society-of-Clinical-Oncology CY MAY 30-JUN 03, 2014 CL Chicago, IL SP Amer Soc Clin Oncol C1 Princess Margaret Canc Ctr, Toronto, ON, Canada. UCL, Inst Canc, London, England. Inst Canc Res, Drug Dev Unit, London SW3 6JB, England. Royal Marsden NHS Fdn Trust, London, England. Edinburgh Canc Res UK Ctr, Edinburgh, Midlothian, Scotland. Prince Wales Hosp, Sydney, NSW, Australia. Peter MacCallum Canc Ctr, Melbourne, Vic, Australia. Univ Hosp Brussels, UZ Brussel, Familial Canc Clin & Med Oncol, Brussels, Belgium. Univ Sydney, Westmead Inst Canc Res, Westmead Millennium Inst, Sydney, NSW 2006, Australia. Tel Aviv Univ, Sackler Fac Med, Ella Inst Res & Treatment Melanoma, Sheba Med Ctr, IL-52621 Tel Hashomer, Israel. Royal Marsden NHS Fdn Trust, Sutton, Surrey, England. Cedars Sinai Med Ctr, Samuel Oschin Comprehens Canc Inst, Los Angeles, CA 90048 USA. NCI, NIH, Bethesda, MD 20892 USA. Royal Melbourne Hosp, Parkville, Vic, Australia. Dana Farber Canc Inst, Boston, MA 02115 USA. Chaim Sheba Med Ctr, Inst Oncol, Breast Canc Unit, IL-52621 Tel Hashomer, Israel. AstraZeneca, Macclesfield, Cheshire, England. AstraZeneca, Wilmington, DE USA. Univ Hlth Network, Princess Margaret Canc Ctr, Toronto, ON, Canada. RI De Greve, Jacques/J-4939-2012 OI De Greve, Jacques/0000-0002-2389-0742 NR 0 TC 0 Z9 0 U1 0 U2 2 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 MAY 20 PY 2014 VL 32 IS 15 SU S MA 5534 PG 1 WC Oncology SC Oncology GA CN7KL UT WOS:000358613203518 ER PT J AU Liebman, MF Brien, W Parulekar, WR Gelmon, KA Shepherd, LE Ligibel, JA Hershman, DL Rastogi, P Mayer, IA Hobday, TJ Lemieux, J Thompson, AM Pritchard, KI Whelan, TJ Mukherjee, S Chalchal, HI Bernstein, V Stambolic, V Chen, BSE Goodwin, PJ AF Liebman, Mira F. Brien, William Parulekar, Wendy R. Gelmon, Karen A. Shepherd, Lois E. Ligibel, Jennifer A. Hershman, Dawn L. Rastogi, Priya Mayer, Ingrid A. Hobday, Timothy J. Lemieux, Julie Thompson, Alastair Mark Pritchard, Kathleen I. Whelan, Timothy Joseph Mukherjee, Som Chalchal, Haji I. Bernstein, Vanessa Stambolic, Vuk Chen, Bingshu E. Goodwin, Pamela Jean CA Univ Toronto TI Vitamin B12 (Vit B12) biochemical (BCH) deficiency (DEF) in non-diabetic breast cancer (BC) patients on NCIC CTG MA.32: A phase III randomized adjuvant BC trial comparing metformin (Met) to placebo (Pl). SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT 50th Annual Meeting of the American-Society-of-Clinical-Oncology CY MAY 30-JUN 03, 2014 CL Chicago, IL SP Amer Soc Clin Oncol C1 Univ Toronto, Univ Hlth Network, Toronto, ON, Canada. Queens Univ, Canc Res Inst, NCIC Clin Trials Grp, Kingston, ON, Canada. Univ British Columbia, British Columbia Canc Agcy, NCIC Clin Trials Grp, Vancouver, BC V5Z 1M9, Canada. Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. Columbia Univ, Med Ctr, New York, NY USA. Natl Surg Adjuvant Breast & Bowel Project, Pittsburgh, PA USA. Univ Pittsburgh, Inst Canc, Pittsburgh, PA USA. Vanderbilt Univ, Sch Med, Vanderbilt Ingram Canc Ctr, Nashville, TN 37212 USA. Mayo Clin, Coll Med, Rochester, MN USA. CHU Quebec, Ctr Rech, Unite Rech Sante Populat, Hop St Sacrement, Quebec City, PQ, Canada. Dundee Canc Ctr, Dundee, Scotland. Sunnybrook Odette Canc Ctr, Toronto, ON, Canada. Univ Toronto, Toronto, ON, Canada. Juravinski Canc Ctr, Hamilton, ON, Canada. Allan Blair Canc Ctr, Regina, SK, Canada. Univ British Columbia, Vancouver Isl Ctr, British Columbia Canc Agcy, Vancouver, BC V5Z 1M9, Canada. Univ Toronto, Princess Margaret Hosp, Univ Hlth Network, Ontario Canc Inst, Toronto, ON, Canada. Univ Toronto, Mt Sinai Hosp, Lunenfeld Tanenbaum Res Inst, Toronto, ON M5G 1X5, Canada. RI Whelan, Timothy/D-3185-2017 NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X EI 1527-7755 J9 J CLIN ONCOL JI J. Clin. Oncol. PD MAY 20 PY 2014 VL 32 IS 15 SU S MA 542 PG 1 WC Oncology SC Oncology GA CN7KL UT WOS:000358613202316 ER PT J AU Lin, NU Gabrail, NY Sarantopoulos, J Schwartzberg, LS Kesari, S Bates, SE Anders, CK Elias, AD Castaigne, JP Iordanova, V Lawrence, B Kurzrock, R AF Lin, Nancy U. Gabrail, Nashat Y. Sarantopoulos, John Schwartzberg, Lee Steven Kesari, Santosh Bates, Susan Elaine Anders, Carey K. Elias, Anthony D. Castaigne, Jean-Paul Iordanova, Vihra Lawrence, Betty Kurzrock, Razelle TI Evaluation of CNS and peripheral antitumor activity of ANG1005 in patients with brain metastases from breast tumors and other advanced solid tumors SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT 50th Annual Meeting of the American-Society-of-Clinical-Oncology CY MAY 30-JUN 03, 2014 CL Chicago, IL SP Amer Soc Clin Oncol C1 Dana Farber Canc Inst, Boston, MA 02115 USA. Gabrail Canc Ctr, Canton, OH USA. Univ Texas Hlth Sci Ctr San Antonio, Canc Therapy & Res Ctr, Inst Drug Dev, San Antonio, TX 78229 USA. Univ Tennessee, Ctr Hlth Sci, Memphis, TN 38163 USA. Univ Calif San Diego, La Jolla, CA 92093 USA. NCI, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. UNC Lineberger Comprehens Canc Ctr, Chapel Hill, NC USA. Univ Colorado, Ctr Canc, Aurora, CO USA. Angiochem Inc, Montreal, PQ, Canada. NR 0 TC 0 Z9 0 U1 0 U2 0 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 MAY 20 PY 2014 VL 32 IS 15 SU S MA 2523 PG 1 WC Oncology SC Oncology GA CN7KL UT WOS:000358613202788 ER PT J AU Liu, J Barry, WT Birrer, MJ Lee, JM Buckanovich, RJ Fleming, GF Rimel, BJ Buss, MK Nattam, SR Hurteau, J Luo, WX Cauy, P Obermayer, E Whalen, C Lee, H Winer, EP Kohn, EC Ivy, SP Matulonis, U AF Liu, Joyce Barry, William Thomas Birrer, Michael J. Lee, Jung-min Buckanovich, Ronald J. Fleming, Gini F. Rimel, B. J. Buss, Mary K. Nattam, Sreenivasa R. Hurteau, Jean Luo, Weixiu Quy, Philippa Obermayer, Elizabeth Whalen, Christin Lee, Hang Winer, Eric P. Kohn, Elise C. Ivy, S. Percy Matulonis, Ursula TI A randomized phase 2 trial comparing efficacy of the combination of the PAR? inhibitor olaparib and the antiangiogenic cediranib against olaparib alone in recurrent platinum-sensitive ovarian cancer. SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT 50th Annual Meeting of the American-Society-of-Clinical-Oncology CY MAY 30-JUN 03, 2014 CL Chicago, IL SP Amer Soc Clin Oncol C1 Dana Farber Canc Inst, Boston, MA 02115 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. NCI, NIH, Bethesda, MD 20892 USA. Univ Michigan, Ann Arbor, MI 48109 USA. Univ Chicago, Med Ctr, Chicago, IL 60637 USA. Cedars Sinai Med Ctr, Los Angeles, CA 90048 USA. Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. Ft Wayne Med Oncol & Hematol, Ft Wayne, IN USA. Univ Chicago, Northshore Univ Hlth Syst, Evanston, IL USA. Dana Farber Canc Inst, IBCSG Stat Ctr, Boston, MA 02115 USA. NCI, Canc Therapy Evaluat Program, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X EI 1527-7755 J9 J CLIN ONCOL JI J. Clin. Oncol. PD MAY 20 PY 2014 VL 32 IS 15 SU S MA LBA5500 PG 1 WC Oncology SC Oncology GA CN7KL UT WOS:000358613201959 ER PT J AU Loupakis, F Cremolini, C Lonardi, S Tomasello, G Ronzoni, M Zaniboni, A Tonini, G Valsuani, C Chiara, S Boni, C Marcucci, L Negri, F Barone, C Vitello, S D'Amico, M Granetto, C Fontanini, G Tomcikova, D Boni, L Falcone, A AF Loupakis, Fotios Cremolini, Chiara Lonardi, Sara Tomasello, Gianluca Ronzoni, Monica Zaniboni, Alberto Tonini, Giuseppe Valsuani, Chiara Chiara, Silvana Boni, Corrado Marcucci, Lorenzo Negri, Francesca Barone, Carlo Vitello, Stefano D'Amico, Mauro Granetto, Cristina Fontanini, Gabriella Tomcikova, Daniela Boni, Luca Falcone, Alfredo TI Subgroup analyses in RAS mutant, BRAF mutant and all-wt mCRC pts treated with FOLFOXIRI plus bevacizumab (bev) or FOLFIRI plus bev in the TRIBE study. SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT 50th Annual Meeting of the American-Society-of-Clinical-Oncology CY MAY 30-JUN 03, 2014 CL Chicago, IL SP Amer Soc Clin Oncol C1 Azienda Osped Univ Pisana, UO Oncol Med 2, Pisa, Italy. Azienda Osped Univ Pisana, UO Oncol Med 2, Ist Toscano Tumori, Pisa, Italy. Ist Oncol Veneto IOV IRCCS, Med Oncol 1, Padua, Italy. Ist Ospitalieri Cremona, Cremona, Italy. Ist Sci San Raffaele, Dipartimento Oncol Med, Milan, Italy. Casa Cura Poliambulanza, Dept Med Oncol, Brescia, Italy. Campus Biomed Univ Rome, Dept Med Oncol, Rome, Italy. Osped Versilia, UO Oncol Med, Viareggio, Italy. Natl Canc Inst, Med Oncol Unit, Genoa, Italy. Santa Maria Nuova Hosp, Reggio Emilia, Italy. USL 5 Pontedera, Div Med Oncol, Pontedera, Italy. Univ Hosp Parma, Med Oncol Unit, Parma, Italy. Univ Cattolica Sacro Cuore, I-00168 Rome, Italy. Osped St Elia, UO Oncol, Caltanissetta, Italy. EO Osped Galliera, Genoa, Italy. Azienda Sanit Osped S Croce & Carle, UO Oncol Med, Cuneo, Italy. Azienda Osped Univ Pisana, Pisa, Italy. Ist Toscano Tumori, Florence, Italy. ITT, AOU Careggi, Clin Trial Coordinating Ctr, Florence, Italy. NR 0 TC 5 Z9 5 U1 0 U2 1 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X EI 1527-7755 J9 J CLIN ONCOL JI J. Clin. Oncol. PD MAY 20 PY 2014 VL 32 IS 15 SU S MA 3519 PG 1 WC Oncology SC Oncology GA CN7KL UT WOS:000358613203035 ER PT J AU Lu, YY Xu, WP Ji, JF Fang, H Sourbier, C Qu, JH Wang, CP Wang, XW Yang, YP Neckers, L AF Lu, Yin Ying Xu, Wanping Ji, Junfang Fang, Hun Sourbier, Carole Qu, Jianhui Wang, Chunping Wang, Xin Wei Yang, Yongping Neckers, Len TI Molecular chaperone HSP90 regulation of the alternative splicing of numb as a clue for HCC progression. SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT 50th Annual Meeting of the American-Society-of-Clinical-Oncology CY MAY 30-JUN 03, 2014 CL Chicago, IL SP Amer Soc Clin Oncol C1 Beijing 302 Hosp, Ctr Therapeut Res Hepatocarcinoma, Beijing, Peoples R China. NCI, Urol Oncol Branch, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. Univ Hawaii, Ctr Canc, Canc Biol Program, Honolulu, HI 96822 USA. NIAAA, Lab Liver Dis, NIH, Rockville, MD 20852 USA. NCI, NIH, Bethesda, MD 20892 USA. Ctr Therapeut Res Hepatocarcinoma, Beijing, Peoples R China. 302 Hosp PLA, Ctr Therapeut Res Hepatocellular Carcinoma, Beijing, Peoples R China. NCI, Liver Carcinogenesis Sect, Lab Human Carcinogenesis, Ctr Canc Res, Bethesda, MD 20892 USA. 302 Mil Hosp China, Beijing, Peoples R China. NCI, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 MAY 20 PY 2014 VL 32 IS 15 SU S MA e15114 PG 1 WC Oncology SC Oncology GA CN7KL UT WOS:000358613200515 ER PT J AU Ma, CX Gao, F Naughton, M Pluard, TJ Sorscher, S Creekmore, AN Guo, ZF Dehdashti, F Park, BH Lockhart, AC Doyle, LA Ellis, MJ Erlanger, B AF Ma, Cynthia X. Gao, Feng Naughton, Michael Pluard, Timothy J. Sorscher, Steven Creekmore, Allison N. Guo, Zhanfang Dehdashti, Farrokh Park, Ben Ho Lockhart, Albert C. Doyle, L. Austin Ellis, Matthew J. Erlanger, Bracha TI A phase I study of the AKT inhibitor MK-2206 plus hormonal therapy in postmenopausal women with estrogen receptor positive (ER plus ) metastatic breast cancer (MBC) SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT 50th Annual Meeting of the American-Society-of-Clinical-Oncology CY MAY 30-JUN 03, 2014 CL Chicago, IL SP Amer Soc Clin Oncol C1 Washington Univ, Sch Med, Siteman Canc Ctr, St Louis, MO USA. Washington Univ, Div Oncol, St Louis, MO USA. Sidney Kimmel Comprehens Canc Ctr Johns Hopkins, Baltimore, MD USA. Washington Univ, St Louis, MO USA. NCI, Rockville, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 MAY 20 PY 2014 VL 32 IS 15 SU S MA 553 PG 1 WC Oncology SC Oncology GA CN7KL UT WOS:000358613202327 ER PT J AU Maher, VE Kacuba, A Ning, YMM Murgo, AJ Ibrahim, A Farrell, AT Keegan, P Justice, RL Pazdur, R AF Maher, Virginia Ellen Kacuba, Alice Ning, Yangmin M. Murgo, Anthony J. Ibrahim, Amna Farrell, Ann T. Keegan, Patricia Justice, Robert L. Pazdur, Richard TI Special protocol assessments: 10 years of experience in FDA's Office of Hematology and Oncology Produets SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT 50th Annual Meeting of the American-Society-of-Clinical-Oncology CY MAY 30-JUN 03, 2014 CL Chicago, IL SP Amer Soc Clin Oncol C1 US FDA, Silver Spring, MD USA. NCI, US FDA, Silver Spring, MD USA. NCI, Div Canc Treatment & Diag, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 MAY 20 PY 2014 VL 32 IS 15 SU S MA e17511 PG 1 WC Oncology SC Oncology GA CN7KL UT WOS:000358613200971 ER PT J AU Malecek, K Grigoryan, A Zhong, S Gu, WJ Johnson, LA Rosenberg, SA Cardozo, T Krogsgaard, M AF Malecek, Karolina Grigoryan, Arsen Zhong, Shi Gu, Wei Jun Johnson, Laura A. Rosenberg, Steven A. Cardozo, Timothy Krogsgaard, Michelle TI Specific increase in T-cell potency via structure-based design of a T-cell receptor for adoptive immunotherapy. SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT 50th Annual Meeting of the American-Society-of-Clinical-Oncology CY MAY 30-JUN 03, 2014 CL Chicago, IL SP Amer Soc Clin Oncol C1 NYU Med Sch, New York, NY USA. Xiangxue Pharmaceut Co, Guangzhou, Guangdong, Peoples R China. NYU, New York, NY USA. Univ Penn, Philadelphia, PA 19104 USA. NCI, Bethesda, MD 20892 USA. New York Univ Langone Med Ctr, New York, NY USA. New York Univ Sch Med, Dept Pathol, New York, NY USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 MAY 20 PY 2014 VL 32 IS 15 SU S MA 3063 PG 1 WC Oncology SC Oncology GA CN7KL UT WOS:000358613202954 ER PT J AU Mamounas, EP White, JR Bandos, H Julian, TB Kahn, AJ Shaitelman, SF Torres, MA McCloskey, SA Vicini, FA Ganz, PA Paik, S Gupta, N Costantino, JP Curran, WJ Wolmark, N AF Mamounas, Eleftherios P. White, Julia R. Bandos, Hanna Julian, Thomas B. Kahn, Atif J. Shaitelman, Simona Flora Torres, Mylin Ann McCloskey, Susan Ann Vicini, Frank A. Ganz, Patricia A. Paik, Soonmyung Gupta, Nilendu Costantino, Joseph P. Curran, Walter John Wolmark, Norman TI NSABP B-51/RTOG 1304: Randomized phase III clinical trial evaluating the role of postmastectomy chest wall and regional nodal XRT (CWRNRT) and post-lumpectomy RNRT in patients (pts) with documented positive axillary (Ax) nodes before neoadjuvant chemotherapy (NC) who convert to pathologically negative Ax nodes after NC. SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT 50th Annual Meeting of the American-Society-of-Clinical-Oncology CY MAY 30-JUN 03, 2014 CL Chicago, IL SP Amer Soc Clin Oncol C1 Natl Surg Adjuvant Breast & Bowel Project NSABP, Orlando, FL USA. Orlando Hlth, UF Hlth Canc Ctr, Orlando, FL USA. Ohio State Univ, Med Ctr, Columbus, OH 43210 USA. NSABP Biostat Ctr, Pittsburgh, PA USA. Univ Pittsburgh, Grad Sch Publ Hlth, Dept Biostat, Pittsburgh, PA 15261 USA. NSABP, Pittsburgh, PA USA. Allegheny Gen Hosp, Allegheny Canc Ctr, Pittsburgh, PA 15212 USA. NSABP, New Brunswick, NJ USA. Rutgers Canc Inst New Jersey, New Brunswick, NJ USA. Univ Texas MD Anderson Canc Ctr, Radiat Therapy Oncol Grp, Houston, TX 77030 USA. NSABP, Atlanta, GA USA. Emory Univ, Winship Canc Inst, Dept Radiat Oncol, Atlanta, GA 30322 USA. NSABP, Los Angeles, CA USA. Univ Calif Los Angeles, Los Angeles, CA USA. NSABP, Beaumont, TX USA. 21st Century Oncol, Farmington Hills, MI USA. Yonsei Univ, Coll Med, Severance Biomed Sci Inst, Pittsburgh, PA USA. Yonsei Univ, Coll Med, Dept Med Oncol, Pittsburgh, PA USA. Ohio State Univ, Radiat Therapy Oncol Grp, Columbus, OH 43210 USA. NSABP Biostat Ctr, Pittsburgh, PA USA. Emory Univ, Winship Canc Inst, Atlanta, GA 30322 USA. NR 0 TC 2 Z9 2 U1 0 U2 0 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 MAY 20 PY 2014 VL 32 IS 15 SU S MA TPS1141 PG 1 WC Oncology SC Oncology GA CN7KL UT WOS:000358613202004 ER PT J AU Massett, HA Atkinson, N Brittle, C Adler, J Roach, N Bailey, R Good, MJ Burgess, D Mooney, MM Abrams, JS AF Massett, Holly A. Atkinson, Nancy Brittle, Christine Adler, Jeanne Roach, Nancy Bailey, Robert Good, Marjorie J. Burgess, Danielle Mooney, Margaret M. Abrams, Jeffrey S. TI A randomized, controlled study comparing NCI's original and revised informed consent templates SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT 50th Annual Meeting of the American-Society-of-Clinical-Oncology CY MAY 30-JUN 03, 2014 CL Chicago, IL SP Amer Soc Clin Oncol C1 NCI, Rockville, MD USA. Westat Corp, Rockville, MD USA. Salter Mitchell, Alexandria, VA USA. Colorectal Canc Coalit, Alexandria, VA USA. Fight Colorectal Canc, Kansas City, MO USA. NCI, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 MAY 20 PY 2014 VL 32 IS 15 SU S MA 6523 PG 1 WC Oncology SC Oncology GA CN7KL UT WOS:000358613203709 ER PT J AU Meany, HJ Dome, J Hinds, PS Bagatell, R Shusterman, S Widemann, BC Stern, E London, WB Kim, A Fox, E Rodriguez-Galindo, C Minturn, JE AF Meany, Holly Jane Dome, Jeffrey Hinds, Pamela S. Bagatell, Rochelle Shusterman, Suzanne Widemann, Brigitte C. Stern, Emily London, Wendy B. Kim, AeRang Fox, Elizabeth Rodriguez-Galindo, Carlos Minturn, Jane E. TI Phase 1 study of sorafenib and irinotecan in pediatric patients with relapsed or refractory solid tumors. SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT 50th Annual Meeting of the American-Society-of-Clinical-Oncology CY MAY 30-JUN 03, 2014 CL Chicago, IL SP Amer Soc Clin Oncol C1 Childrens Natl Med Ctr, Washington, DC 20010 USA. Childrens Hosp, Philadelphia, PA 19104 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. NCI, Pediat Oncol Branch, NIH, Bethesda, MD 20892 USA. Boston Childrens Hosp, Dana Farber Canc Inst, Boston, MA USA. NR 0 TC 2 Z9 2 U1 0 U2 0 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 MAY 20 PY 2014 VL 32 IS 15 SU S MA 10052 PG 1 WC Oncology SC Oncology GA CN7KL UT WOS:000358613204591 ER PT J AU Merchant, MS Bernstein, DB Delbrook, C Wright, M Mackall, C AF Merchant, Melinda S. Bernstein, Donna B. Delbrook, Cindy Wright, Matthew Mackall, Crystal TI Metastatic melanoma presenting during childhood: NCI Pediatric Oncology Branch experience. SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT 50th Annual Meeting of the American-Society-of-Clinical-Oncology CY MAY 30-JUN 03, 2014 CL Chicago, IL SP Amer Soc Clin Oncol C1 NCI, NIH, Bethesda, MD 20892 USA. NCI, Bethesda, MD 20892 USA. NCI, NIH, Rockville, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 MAY 20 PY 2014 VL 32 IS 15 SU S MA 10075 PG 1 WC Oncology SC Oncology GA CN7KL UT WOS:000358613204614 ER PT J AU Moore, HCF Unger, JM Phillips, KA Boyle, FM Nitre, E Porter, DJ Francis, PA Minasian, LM Gelber, RD Goldstein, LJ Gomez, HL Vallejos, C Partridge, AH Dakhil, SR Martino, S Barlow, WE Fabian, CJ Meyskens, FL Hortobagyi, GN Albain, KS AF Moore, Halle C. F. Unger, Joseph M. Phillips, Kelly-Anne Boyle, Frances M. Nitre, Erika Porter, David James Francis, Prudence A. Minasian, Lori M. Gelber, Richard D. Goldstein, Lori J. Gomez, Henry Leonidas Vallejos, Carlos Partridge, Ann H. Dakhil, Shaker R. Martino, Silvana Barlow, William E. Fabian, Carol J. Meyskens, Frank L. Hortobagyi, Gabriel N. Albain, Kathy S. TI Phase III trial (Prevention of Early Menopause Study [POEMS]-SWOG S0230) of LHRH analog during chemotherapy (CT) to reduce ovarian failure in early-stage, hormone receptor-negative breast cancer: An international Intergroup trial of SWOG, IBCSG, ECOG, and CALGB (Alliance). SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT 50th Annual Meeting of the American-Society-of-Clinical-Oncology CY MAY 30-JUN 03, 2014 CL Chicago, IL SP Amer Soc Clin Oncol C1 Cleveland Clin, Cleveland, OH 44106 USA. SWOG Stat Ctr, Seattle, WA USA. Peter MacCallum Canc Ctr, Melbourne, Vic, Australia. Mater Hosp, Sydney, NSW, Australia. Natl Inst Oncol, Budapest, Hungary. Auckland City Hosp, Dept Oncol, Auckland, New Zealand. Peter MacCallum Canc Ctr, East Melbourne, Australia. NCI, Bethesda, MD 20892 USA. Dana Farber Canc Inst, Dept Biostat & Computat Biol, Boston, MA 02115 USA. Fox Chase Canc Ctr, Philadelphia, PA 19111 USA. Inst Nacl Enfermedades Neoplas, Lima, Peru. ONCOSALUD, Lima, Peru. Dana Farber Canc Inst, Boston, MA 02115 USA. Wichita Community Clin Oncol Program, Wichita, KS USA. Angeles Clin & Res Inst, Santa Monica, CA USA. Canc Res & Biostat, Seattle, WA USA. Univ Kansas, Med Ctr, Kansas City, KS 66103 USA. Chao Family Comprehens Canc Ctr, Orange, CA USA. Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA. Loyola Univ, Med Ctr, Maywood, IL 60153 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 MAY 20 PY 2014 VL 32 IS 15 SU S MA LBA505 PG 1 WC Oncology SC Oncology GA CN7KL UT WOS:000358613201957 ER PT J AU Ning, YMM Kim, T Maher, VE Ibrahim, A Murgo, AJ Farrell, AT Keegan, P Justice, RL Pazdur, R AF Ning, Yangmin M. Kim, Tamy Maher, Virginia Ellen Ibrahim, Amna Murgo, Anthony J. Farrell, Ann T. Keegan, Patricia Justice, Robert L. Pazdur, Richard TI FDA breakthrough therapy designation of oncology-products: The first-year experience. SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT 50th Annual Meeting of the American-Society-of-Clinical-Oncology CY MAY 30-JUN 03, 2014 CL Chicago, IL SP Amer Soc Clin Oncol C1 NCI, US FDA, Silver Spring, MD USA. US FDA, Rockville, MD 20857 USA. US FDA, Silver Spring, MD USA. NCI, Div Canc Treatment & Diag, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 MAY 20 PY 2014 VL 32 IS 15 SU S MA e17502 PG 1 WC Oncology SC Oncology GA CN7KL UT WOS:000358613200964 ER PT J AU O'Reilly, EM Lowery, MA Segal, MF Smith, SC Moore, MJ Kindler, HL Golan, T Segal, A Salo-Mullen, EE Hollywood, E Epstein, AS Capanu, M Moynahan, ME Fusco, A Stadler, ZK Do, RKG Chen, AP Yu, KH Tang, LH Kelsen, DP AF O'Reilly, Eileen Mary Lowery, Maeve Aine Segal, Michal Fani Smith, Sloane C. Moore, Malcolm J. Kindler, Hedy Lee Golan, Talia Segal, Amiel Salo-Mullen, Erin E. Hollywood, Ellen Epstein, Andrew S. Capanu, Marinela Moynahan, Mary Ellen Fusco, Anne Stadler, Zsofia Kinga Do, Richard Kinh Gian Chen, Alice P. Yu, Kenneth H. Tang, Laura H. Kelsen, David Paul TI Phase IB trial of cisplatin (C), gemcitabine (G), and veliparib (V) in patients with known or potential BRCA or PALB2-mutated pancreas adenocarcinoma (PC). SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT 50th Annual Meeting of the American-Society-of-Clinical-Oncology CY MAY 30-JUN 03, 2014 CL Chicago, IL SP Amer Soc Clin Oncol C1 Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. Princess Margaret Canc Ctr, Toronto, ON, Canada. Univ Chicago, Chicago, IL 60637 USA. Sheba Med Ctr, Tel Hashomer, Israel. Shaare Zedek Med Ctr, Inst Oncol, Jerusalem, Israel. Mem Sloan Kettering Canc Ctr, Dept Med, Clin Genet Serv, New York, NY 10021 USA. Natl Canc Inst, Bethesda, MD USA. Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. Weill Cornell Med Coll, New York, NY USA. Mem Sloan Kettering Canc Ctr, Dept Pathol, New York, NY 10021 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 MAY 20 PY 2014 VL 32 IS 15 SU S MA 4023 PG 1 WC Oncology SC Oncology GA CN7KL UT WOS:000358613203186 ER PT J AU O'Sullivan, CCM Bradbury, I De Azambuja, E Perez, EA Rastogi, P Spielmann, M Joensuu, H Ballman, KV Costantino, JP Delaloge, S Zardavas, D Piccart-Gebhart, MJ Zujewski, J Holmes, EM Gelber, RD AF O'Sullivan, Ciara Catherine Maria Bradbury, Ian De Azambuja, Evandro Perez, Edith A. Rastogi, Priya Spielmann, Marc Joensuu, Heikki Ballman, Karla V. Costantino, Joseph P. Delaloge, Suzette Zardavas, Dimitrios Piccart-Gebhart, Martine J. Zujewski, JoAnne Holmes, Eileen McCormick Gelber, Richard D. TI Efficacy of adjuvant trastuzumab (T) compared with no T for patients (pts) with HER2-positive breast cancer and tumors <= 2cm: A meta-analysis of the randomized trastuzumab trials. SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT 50th Annual Meeting of the American-Society-of-Clinical-Oncology CY MAY 30-JUN 03, 2014 CL Chicago, IL SP Amer Soc Clin Oncol C1 NCI, Bethesda, MD 20892 USA. Fronfier Sci, Kincraig, England. Univ Libre Bruxelles, Inst Jules Bordet, Brussels, Belgium. Mayo Clin, Jacksonville, FL 32224 USA. Univ Pittsburgh, Med Ctr, Pittsburgh, PA USA. Inst Gustave Roussy, Villejuif, France. Univ Helsinki, Cent Hosp, Dept Oncol, Helsinki, Finland. Mayo Clin, Rochester, MN USA. Univ Pittsburgh, Grad Sch Publ Hlth, Natl Surg Adjuvant Breast & Bowel Project, Biostat Ctr, Pittsburgh, PA USA. Univ Pittsburgh, Grad Sch Publ Hlth, Dept Biostat, Pittsburgh, PA USA. Inst Cancerol Gustave Roussy, Villejuif, France. Breast Int Grp, Inst Jules Bordet, Brussels, Belgium. Frontier Sci Scotland, Kingussie, Inverness, Scotland. Dana Farber Canc Inst, Dept Biostat & Computat Biol, Boston, MA 02115 USA. NR 0 TC 1 Z9 1 U1 0 U2 1 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X EI 1527-7755 J9 J CLIN ONCOL JI J. Clin. Oncol. PD MAY 20 PY 2014 VL 32 IS 15 SU S MA 508 PG 1 WC Oncology SC Oncology GA CN7KL UT WOS:000358613202282 ER PT J AU Ojemuyiwa, MA Karzai, F Shah, AA Theoret, MR Harold, N Chun, G Figg, WD Apolo, AB Price, DK Madan, RA Gulley, JL Dahut, WL AF Ojemuyiwa, Michelle A. Karzai, Fatima Shah, Avani Atul Theoret, Marc Robert Harold, Nancy Chun, Guinevere Figg, William Douglas Apolo, Andrea Borghese Price, Douglas K. Madan, Ravi Amrit Gulley, James L. Dahut, William L. TI A safety study of trebananib (AMG 386) and abiraterone in metastatic castration-resistant prostate cancer (mCRPC). SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT 50th Annual Meeting of the American-Society-of-Clinical-Oncology CY MAY 30-JUN 03, 2014 CL Chicago, IL SP Amer Soc Clin Oncol C1 Walter Reed Natl Mil Med Ctr, Bethesda, MD USA. NCI, Bethesda, MD 20892 USA. NCI, NIH, Bethesda, MD 20892 USA. NCI, Clin Ctr, NIH, Bethesda, MD 20892 USA. NCI, Mol Pharmacol Sect, NIH, Bethesda, MD 20892 USA. RI Gulley, James/K-4139-2016; Figg Sr, William/M-2411-2016 OI Gulley, James/0000-0002-6569-2912; NR 0 TC 0 Z9 0 U1 0 U2 0 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 MAY 20 PY 2014 VL 32 IS 15 SU S MA 5074 PG 1 WC Oncology SC Oncology GA CN7KL UT WOS:000358613203466 ER PT J AU Parsons, HM Schmidt, S Harlan, LC Kent, EE Lynch, C Smith, AW Keegan, THM AF Parsons, Helen M. Schmidt, Susanne Harlan, Linda C. Kent, Erin E. Lynch, Charles Smith, Ashley Wilder Keegan, Theresa H. M. TI Young and uninsured: Insurance patterns of recently diagnosed adolescent and young adult cancer survivors in the AYA HOPE study. SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT 50th Annual Meeting of the American-Society-of-Clinical-Oncology CY MAY 30-JUN 03, 2014 CL Chicago, IL SP Amer Soc Clin Oncol C1 Univ Texas Hlth Sci Ctr San Antonio, San Antonio, TX 78229 USA. NCI, Bethesda, MD 20892 USA. NCI, Rockville, MD USA. Univ Iowa, Iowa City, IA USA. Canc Prevent Inst Calif, Fremont, CA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 MAY 20 PY 2014 VL 32 IS 15 SU S MA 10086 PG 1 WC Oncology SC Oncology GA CN7KL UT WOS:000358613204625 ER PT J AU Peppone, LJ Janelsins, MC Flannery, MA Tejani, MA Peoples, AR Kamen, CS Atkins, JN Giguere, JK Gaur, R Frizzell, B Mustian, KM AF Peppone, Luke Joseph Janelsins, Michelle Christine Flannery, Marie Anne Tejani, Mohamedtaki Abdulaziz Peoples, Anita Roselyn Kamen, Charles Stewart Atkins, James Norman Giguere, Jeffrey K. Gaur, Rakesh Frizzell, Bart Mustian, Karen Michelle TI Cancer patients and their information needs for prediction of symptom burden during and after treatment: Implications for symptom management. SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT 50th Annual Meeting of the American-Society-of-Clinical-Oncology CY MAY 30-JUN 03, 2014 CL Chicago, IL SP Amer Soc Clin Oncol C1 Univ Rochester, Med Ctr, Dept Surg, Rochester, NY 14642 USA. Univ Rochester, Med Ctr, Rochester, NY 14642 USA. Natl Surg Adjuvant Breast & Bowel Project, Goldsboro, NC USA. SCCC CCOP, Goldsboro, NC USA. Canc Ctr Carolinas, Seneca, SC USA. St Lukes Canc Inst, Kansas City, MO USA. High Point Reg Canc Ctr, High Point, NC USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 MAY 20 PY 2014 VL 32 IS 15 SU S MA 9650 PG 1 WC Oncology SC Oncology GA CN7KL UT WOS:000358613204534 ER PT J AU Phillips, AA Fields, P Hermine, O Taylor, G DelloukIna, ML Horwitz, SM Ramos, JC Menlane, JC Barta, SK Or, KM Kurman, MR Saunders, A Grebennik, DO Conlon, K AF Phillips, Adrienne Alise Fields, Paul Hermine, Olivier Taylor, Graham DelloukIna, Maria L. Horwitz, Steven M. Ramos, Juan Carlos Menlane, Jean Cafame Barta, Stefan K. Or, Karen M. Kurman, Michael R. Saunders, Andrew Grebennik, Dmitri O. Conlon, Kevin TI Anti-CCR4 monoclonal antibody KW-0761 (mogamulizumab) or investigator's choice of chemotherapy in subjects with relapsed or refractory adult T-cell leukemia-lymphoma (ATL) SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT 50th Annual Meeting of the American-Society-of-Clinical-Oncology CY MAY 30-JUN 03, 2014 CL Chicago, IL SP Amer Soc Clin Oncol C1 Columbia Univ, New York, NY USA. Guys Hosp, London SE1 9RT, England. Hop Necker Enfants Malad, Paris, France. St Marys Hosp, London, England. Cedars Sinai Med Ctr, Los Angeles, CA 90048 USA. Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. Univ Miami, Miller Sch Med, Miami, FL 33136 USA. CHU Ft France, Fort De France, Martinique. Montefiore Med Ctr, Albert Einstein Coll Med, Bronx, NY 10467 USA. Kyowa Hakko Kirin Pharma, Princeton, NJ USA. Kyowa Hakko Kirin Pharma Inc, Upper Saddle River, NJ USA. Kyowa Hakko Kirin Pharma Inc, Edinburgh, Midlothian, Scotland. Kyowa Hakko Kirin Pharma Inc, Princeton, NJ USA. NCI, Bethesda, MD 20892 USA. NR 0 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 MAY 20 PY 2014 VL 32 IS 15 SU S MA TPS8622 PG 1 WC Oncology SC Oncology GA CN7KL UT WOS:000358613202224 ER PT J AU Piccart-Gebhart, MJ Holmes, AP Baselga, J De Azambuja, E Dueck, AC Viale, G Zujewski, JA Goldhirsch, A Santillana, S Pritchard, KI Wolff, AC Jackisch, C Lang, I Untch, M Smith, IE Boyle, F Xu, BH Gomez, HL Gelber, RD Perez, EA AF Piccart-Gebhart, Martine J. Holmes, Andrew Peter Baselga, Jose De Azambuja, Evandro Dueck, Amylou C. Viale, Giuseppe Zujewski, Jo Anne Goldhirsch, Aron Santillana, Sergio Pritchard, Kathleen I. Wolff, Antonio C. Jackisch, Christian Lang, Istvan Untch, Michael Smith, Ian E. Boyle, Frances Xu, Binghe Gomez, Henry Leonidas Gelber, Richard D. Perez, Edith A. TI First results from the phase III ALTTO trial (BIG 2-06; NCCTG [Alliance] N063D) comparing one year of anti-HER2 therapy with lapatinib alone (L), trastuzumab alone (T), their sequence (T -> L), or their combination T plus L) in the adjuvant treatment of HER2-positive early breast cancer (EBC). SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT 50th Annual Meeting of the American-Society-of-Clinical-Oncology CY MAY 30-JUN 03, 2014 CL Chicago, IL SP Amer Soc Clin Oncol C1 Inst Jules Bordet, Breast Int Grp, B-1000 Brussels, Belgium. Frontier Sci Scotland Ltd, Kincraig, Scotland. Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. Univ Libre Bruxelles, Inst Jules Bordet, Brussels, Belgium. Mayo Clin, Scottsdale, AZ USA. European Inst Oncol, Div Pathol, Milan, Italy. NCI, Bethesda, MD 20892 USA. European Inst Oncol, Div Med Oncol, Milan, Italy. GlaxoSmithKline, Malvern, PA USA. Sunnybrook Odette Canc Ctr, Toronto, ON, Canada. Univ Toronto, Toronto, ON, Canada. Johns Hopkins Univ Hosp, Baltimore, MD 21287 USA. Sidney Kimmel Comprehens Canc Ctr Johns Hopkins, Baltimore, MD USA. Sane Kliniken Offenbach, Offenbach, Germany. Orszagos Onkol Intezet, Budapest, Hungary. Helios Klinikum Berlin Buch, Berlin, Germany. Royal Marsden NHS Fdn Trust, London, England. Univ Sydney, Mater Hosp, Patricia Ritchie Ctr Canc Care & Res, Sydney, NSW 2006, Australia. Chinese Acad Med Sci, Canc Hosp, Beijing 100730, Peoples R China. Inst Nacl Enfermedades Neoplas, Lima, Peru. Dana Farber Canc Inst, Dept Biostat & Computat Biol, Boston, MA 02115 USA. Mayo Clin, Jacksonville, FL 32224 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 MAY 20 PY 2014 VL 32 IS 15 SU S MA LBA4 PG 1 WC Oncology SC Oncology GA CN7KL UT WOS:000358613201956 ER PT J AU Pichun, MEB Bala, S Edgerly, M Wilkerson, J Velarde, M Kotz, HL Bates, SE Fojo, AT AF Pichun, Mauricio Emmanuel Burotto Bala, Sanjeeve Edgerly, Maureen Wilkerson, Julia Velarde, Margarita Kotz, Herbert L. Bates, Susan Elaine Fojo, Antonio Tito TI Phase 2 clinical trial of ixabepilone in metastatic cervical carcinoma. SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT 50th Annual Meeting of the American-Society-of-Clinical-Oncology CY MAY 30-JUN 03, 2014 CL Chicago, IL SP Amer Soc Clin Oncol C1 NCI, NIH, Bethesda, MD 20892 USA. NIH, Bethesda, MD 20892 USA. NCI, Med Oncol Branch, Bethesda, MD 20892 USA. NCI, Med Oncol Branch, Ctr Canc Res, Bethesda, MD 20892 USA. NCI, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 MAY 20 PY 2014 VL 32 IS 15 SU S MA 5593 PG 1 WC Oncology SC Oncology GA CN7KL UT WOS:000358613203577 ER PT J AU Polley, E Monks, A Morris, J Rapisarda, A Kaur, G Mertins, S Connelly, J Slivers, T Delosh, R Laudeman, J Ogle, C Reinhart, R Evans, D Teicher, BA AF Polley, Eric Monks, Anne Morris, Joel Rapisarda, Annemarie Kaur, Gurmeet Mertins, Susan Connelly, John Slivers, Thomas Delosh, Rene Laudeman, Julie Ogle, Chad Reinhart, Russell Evans, David Teicher, Beverly A. TI Sarcoma gene expression and response to approved and investigational agents: Focus on osteosaccoma SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT 50th Annual Meeting of the American-Society-of-Clinical-Oncology CY MAY 30-JUN 03, 2014 CL Chicago, IL SP Amer Soc Clin Oncol C1 NCI, Div Canc Treatment & Diag, Rockville, MD USA. SAIC Frederick Inc, Natl Canc Inst Frederick, Frederick, MD USA. NCI, DCTD, Bethesda, MD 20892 USA. Natl Lab Canc Res, Mol Pharmacol Branch, Frederick, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 MAY 20 PY 2014 VL 32 IS 15 SU S MA e22067 PG 1 WC Oncology SC Oncology GA CN7KL UT WOS:000358613201801 ER PT J AU Puhalla, S Beumer, JH Pahuja, S Appleman, LJ Tawbi, HAH Stoller, RG Lee, JJ Lin, Y Kiesel, B Yu, J Tan, AR Belani, CP Chew, HK Garcia, AA Morgan, R Giranda, VL Shepherd, SP Chen, AP Chu, E AF Puhalla, Shannon Beumer, Jan Hendrik Pahuja, Shalu Appleman, Leonard Joseph Tawbi, Hussein Abdul-Hassan Stoller, Ronald G. Lee, James J. Lin, Yan Kiesel, Brian Yu, Jing Tan, Antoinette R. Belani, Chandra Prakash Chew, Helen K. Garcia, Agustin A. Morgan, Robert Giranda, Vincent L. Shepherd, Stacie Peacock Chen, Alice P. Chu, Edward TI Final results of a phase 1 study of single-agent veliparib (V) in patients (pis) with either BRCA1/2-mutated cancer (BRCA plus ), platinum-refractory ovarian, or basal-like breast cancer (BRCA-wt). SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT 50th Annual Meeting of the American-Society-of-Clinical-Oncology CY MAY 30-JUN 03, 2014 CL Chicago, IL SP Amer Soc Clin Oncol C1 Univ Pittsburgh, Magee Womens Hosp, Med Ctr, Womens Canc Program, Pittsburgh, PA 15213 USA. Univ Pittsburgh, Inst Canc, Pittsburgh, PA USA. Univ Pittsburgh, Med Ctr, Pittsburgh, PA USA. Univ Pittsburgh, Magee Womens Hosp, Pittsburgh, PA 15213 USA. Rutgers Canc Inst New Jersey, New Brunswick, NJ USA. Penn State Hershey Canc Inst, Hershey, PA USA. Univ Calif Davis, Sacramento, CA 95817 USA. Univ So Calif, Los Angeles, CA USA. City Hope Natl Med Ctr, Duarte, CA USA. Abbott Labs, Abbott Pk, IL 60064 USA. NCI, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 MAY 20 PY 2014 VL 32 IS 15 SU S MA 2570 PG 1 WC Oncology SC Oncology GA CN7KL UT WOS:000358613202835 ER PT J AU Reiss, KA Herman, JM Zahurak, M Brade, AM Dawson, LA Scardina, A Joffe, C Petito, E Hacker-Prietz, A Chen, AP Temkin, SM Horiba, N Siu, LL Azad, NS AF Reiss, Kim Anna Herman, Joseph M. Zahurak, Marianna Brade, Anthony M. Dawson, Laura A. Scardina, Angela Joffe, Caitlin Petito, Emily Hacker-Prietz, Amy Chen, Alice P. Temkin, Sarah Madhu Horiba, Naomi Siu, Lillian L. Azad, Nilofer Saba TI A phase I study of veliparib (ABT-888) in combination with low-dose fractionated whole abdominal radiation therapy (LDFWAR) in patients with advanced solid malignancies and peritoneal carcinomatosis. SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT 50th Annual Meeting of the American-Society-of-Clinical-Oncology CY MAY 30-JUN 03, 2014 CL Chicago, IL SP Amer Soc Clin Oncol C1 Johns Hopkins Univ, Sch Med, Baltimore, MD USA. Sidney Kimmel Comprehens Canc Ctr Johns Hopkins, Baltimore, MD USA. Univ Toronto, Princess Margaret Hosp, Toronto, ON, Canada. Princess Margaret Hosp, Toronto, ON M4X 1K9, Canada. NCI, Bethesda, MD 20892 USA. Univ Maryland, Baltimore, MD 21201 USA. Sidney Kimmel Comprehens Canc Ctr, Baltimore, MD USA. NR 0 TC 1 Z9 1 U1 0 U2 0 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 MAY 20 PY 2014 VL 32 IS 15 SU S MA 4139 PG 1 WC Oncology SC Oncology GA CN7KL UT WOS:000358613203301 ER PT J AU Rodriguez, J Patel, S Alpaugh, RK Palazzo, J Berger, AC Avery, TP Jaslow, RJ Anne, PR Simone, NL Tsangaris, TN Cristofanilli, M AF Rodriguez, Joanna Patel, Sheel Alpaugh, R. Katherine Palazzo, Juan Berger, Adam C. Avery, Tiffany P. Jaslow, Rebecca J. Anne, Pramila R. Simone, Nicole Lynn Tsangaris, Theodore N. Cristofanilli, Massimo TI A retrospective review of clinical and pathologic aspects of inflammatory breast cancer: Clues for risk-adapted monitoring and therapy. SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT 50th Annual Meeting of the American-Society-of-Clinical-Oncology CY MAY 30-JUN 03, 2014 CL Chicago, IL SP Amer Soc Clin Oncol C1 Thomas Jefferson Univ, Kimmel Canc Ctr, Dept Med Oncol, Philadelphia, PA 19107 USA. Thomas Jefferson Univ Hosp, Philadelphia, PA 19107 USA. Fox Chase Canc Ctr, Philadelphia, PA 19111 USA. Thomas Jefferson Univ, Jefferson Med Coll, Dept Surg, Philadelphia, PA 19107 USA. Thomas Jefferson Univ, Philadelphia, PA 19107 USA. Thomas Jefferson Univ, Dept Radiat Oncol, Kimmel Canc Ctr, Philadelphia, PA 19107 USA. NCI, Bethesda, MD 20892 USA. Sidney Kimmel Comprehens Canc Ctr Johns Hopkins, Baltimore, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 MAY 20 PY 2014 VL 32 IS 15 SU S MA e11506 PG 1 WC Oncology SC Oncology GA CN7KL UT WOS:000358613200008 ER PT J AU Rubinstein, WS Kattman, BL Malheiro, AJ Lee, JM Maglott, DR Hem, V Ovetsky, M Song, GF Wallin, C Katz, KS Villamarin-Salomon, R Gu, BS Fomous, C Ostell, JM AF Rubinstein, Wendy S. Kattman, Brandi L. Malheiro, Adriana J. Lee, Jennifer M. Maglott, Donna R. Hem, Vichet Ovetsky, Michael Song, Guangfeng Wallin, Craig Katz, Kenneth S. Villamarin-Salomon, Ricardo Gu, Baoshan Fomous, Cathy Ostell, James M. TI The NIH genetic testing registry: Hereditary, pharmacogenetic, and somatic tests for oncology practice SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT 50th Annual Meeting of the American-Society-of-Clinical-Oncology CY MAY 30-JUN 03, 2014 CL Chicago, IL SP Amer Soc Clin Oncol C1 [Rubinstein, Wendy S.; Kattman, Brandi L.; Malheiro, Adriana J.; Lee, Jennifer M.; Maglott, Donna R.; Hem, Vichet; Ovetsky, Michael; Song, Guangfeng; Wallin, Craig; Katz, Kenneth S.; Villamarin-Salomon, Ricardo; Gu, Baoshan; Fomous, Cathy; Ostell, James M.] NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X EI 1527-7755 J9 J CLIN ONCOL JI J. Clin. Oncol. PD MAY 20 PY 2014 VL 32 IS 15 SU S MA 11104 PG 1 WC Oncology SC Oncology GA CN7KL UT WOS:000358613204837 ER PT J AU Sargent, DJ Shi, Q Yothers, G Tejpar, S Bertagnolli, MM Thibodeau, SN Andre, T Labianca, R Gallinger, S Hamilton, SR Monges, G Pogue-Geile, KL Paik, S Klingbiel, D Roth, A Pavey, ES Kim, GP Sinicrope, FA AF Sargent, Daniel J. Shi, Qian Yothers, Greg Tejpar, Sabine Bertagnolli, Monica M. Thibodeau, Stephen N. Andre, Thierry Labianca, Roberto Gallinger, Steven Hamilton, Stanley R. Monges, Genevieve Pogue-Geile, Katherine L. Paik, Soonmyung Klingbiel, Dirk Roth, Arnaud Pavey, Emily S. Kim, George P. Sinicrope, Frank A. CA ACCENT Collaborative Grp TI Prognostic impact of deficient mismatch repair (dMMR) in 7,803 stage II/III colon cancer (CC) patients (pts): A pooled individual pt data analysis of 17 adjuvant trials in the ACCENT database. SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT 50th Annual Meeting of the American-Society-of-Clinical-Oncology CY MAY 30-JUN 03, 2014 CL Chicago, IL SP Amer Soc Clin Oncol C1 Mayo Clin, Rochester, MN USA. Natl Surg Adjuvant Breast & Bowel Project Biostat, Pittsburgh, PA USA. Univ Pittsburgh Grad Sch Publ Hlth, Dept Biostat, Pittsburgh, PA USA. Univ Leuven, KUL, Leuven, Belgium. Brigham & Womens Hosp, Boston, MA 02115 USA. Mayo Clin Coll Med, Rochester, MN USA. Hop La Pitie Salpetriere, Paris, France. Osped Riuniti Bergamo, Dept Oncol, I-24100 Bergamo, Italy. Mt Sinai Hosp, Toronto, ON M5G 1X5, Canada. Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA. Inst J Paoli I Calmettes, F-13009 Marseille, France. NSABP, Pittsburgh, PA USA. Yonsei Univ Coll Med, NSABP, Pittsburgh, PA USA. Yonsei Univ Coll Med, Severance Biomed Sci Inst, Pittsburgh, PA USA. Yonsei Univ Coll Med, Dept Med Oncol, Pittsburgh, PA USA. Swiss Grp Clin Canc Res, Bern, Switzerland. Univ Hosp Geneva, Geneva, Switzerland. Mayo Clin, Jacksonville, FL 32224 USA. NR 0 TC 5 Z9 5 U1 0 U2 1 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X EI 1527-7755 J9 J CLIN ONCOL JI J. Clin. Oncol. PD MAY 20 PY 2014 VL 32 IS 15 SU S MA 3507 PG 1 WC Oncology SC Oncology GA CN7KL UT WOS:000358613203023 ER PT J AU Seibel, N Hunsberger, S O'Mara, AM Budd, T Friedman, SH Finnigan, S Lewis, DR Freyer, DR AF Seibel, Nita Hunsberger, Sally O'Mara, Ann M. Budd, Troy Friedman, Steven H. Finnigan, Shanda Lewis, Denise R. Freyer, David Robert TI Adolescent and young adult oncology (AYAO) patient enrollments onto National Cancer Institute (NCI)-supported trials from 2000 to 2010. SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT 50th Annual Meeting of the American-Society-of-Clinical-Oncology CY MAY 30-JUN 03, 2014 CL Chicago, IL SP Amer Soc Clin Oncol C1 NCI, Canc Therapy Evaluat Program, Bethesda, MD 20892 USA. NCI, Bethesda, MD 20892 USA. Canc Prevent Div, Bethesda, MD USA. NCI, Rockville, MD USA. Childrens Hosp, Los Angeles, CA 90027 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 MAY 20 PY 2014 VL 32 IS 15 SU S MA 10058 PG 1 WC Oncology SC Oncology GA CN7KL UT WOS:000358613204597 ER PT J AU Shoushtari, AN D'Angelo, SP Keohan, ML Dickson, MA Gounder, MM Abdullah, AK Erinjeri, JP Bluth, MJ Ustoyev, Y Condy, MM Streicher, H Takebe, N DeMatteo, RP Schwartz, GK Tap, WD Carvajal, RD AF Shoushtari, Alexander Noor D'Angelo, Sandra P. Keohan, Mary Louise Dickson, Mark Andrew Gounder, Mrinal M. Abdullah, Abdul Karim Erinjeri, Joseph Patrick Bluth, Mark J. Ustoyev, Yelena Condy, Mercedes M. Streicher, Howard Takebe, Naoko DeMatteo, Ronald P. Schwartz, Gary K. Tap, William D. Carvajal, Richard D. TI Combined KIT and CTLA-4 blockade in patients with refractory GIST and other advanced sarcomas. SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT 50th Annual Meeting of the American-Society-of-Clinical-Oncology CY MAY 30-JUN 03, 2014 CL Chicago, IL SP Amer Soc Clin Oncol C1 Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. NCI, Div Canc Treatment & Diag, Bethesda, MD 20892 USA. Invest Drug Branch, Canc Therapy Evaluat Program, Rockville, MD USA. Columbia Univ, Med Ctr, New York, NY USA. NR 0 TC 0 Z9 0 U1 1 U2 2 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 MAY 20 PY 2014 VL 32 IS 15 SU S MA 10521 PG 1 WC Oncology SC Oncology GA CN7KL UT WOS:000358613204654 ER PT J AU Singh, H Heery, CR Marte, JL Farsaci, B Madan, RA Coyne, GHO Palena, C Rodell, TC Schlom, J Gulley, JL AF Singh, Harpreet Heery, Christopher Ryan Marte, Jennifer L. Farsaci, Bonedetto Madan, Ravi Amrit Coyne, Geraldine Helen O'Sullivan Palena, Claudia Rodell, Timothy C. Schlom, Jeffrey Gulley, James L. TI A phase I study of a yeast-based therapeutic cancer vaccine, GI-6301, targeting brachyury in patients with metastatic carcinoma SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT 50th Annual Meeting of the American-Society-of-Clinical-Oncology CY MAY 30-JUN 03, 2014 CL Chicago, IL SP Amer Soc Clin Oncol C1 NCI, Genitourinary Malignancies Branch, Bethesda, MD 20892 USA. NCI, NIH, Bethesda, MD 20892 USA. NCI, Lab Tumor Immunol & Biol, NIH, Bethesda, MD 20892 USA. Ctr Canc Res, Lab Tumor Immunol & Biol, Bethesda, MD USA. NCI, NIH, Bethesda, MD 20892 USA. NCI, Genitourinary Malignancies Branch, NIH, Bethesda, MD 20892 USA. NCI, Lab Tumor Immunol & Biol, Bethesda, MD 20892 USA. Globeimmune Inc, Louisville, CO USA. RI Gulley, James/K-4139-2016 OI Gulley, James/0000-0002-6569-2912 NR 0 TC 0 Z9 0 U1 0 U2 0 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 MAY 20 PY 2014 VL 32 IS 15 SU S MA e14026 PG 1 WC Oncology SC Oncology GA CN7KL UT WOS:000358613200276 ER PT J AU Soliman, HH Minton, SE Ismail-Khan, R Han, HS Janssen, W Vahanlan, NN Link, CJ Strelcher, H Sullivan, D Antonia, SJ AF Soliman, Hatem Hussein Minton, Susan E. Ismail-Khan, Roohi Han, Hyo S. Janssen, William Vahanlan, Nicholas N. Link, Charles J. Strelcher, Howard Sullivan, Daniel Antonia, Scott Joseph TI A phase 2 study of Ad.p53 DC vaccine in combination with indoximod in metastatic solid tumors. SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT 50th Annual Meeting of the American-Society-of-Clinical-Oncology CY MAY 30-JUN 03, 2014 CL Chicago, IL SP Amer Soc Clin Oncol C1 Univ S Florida, Coll Med, H Lee Moffitt Canc Ctr & Res Inst, Tampa, FL 33612 USA. Univ S Florida, H Lee Moffitt Canc Ctr, Tampa, FL 33682 USA. NewLink Genet, Ames, IA USA. NCI, Div Canc Treatment & Diag, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X EI 1527-7755 J9 J CLIN ONCOL JI J. Clin. Oncol. PD MAY 20 PY 2014 VL 32 IS 15 SU S MA TPS3125 PG 1 WC Oncology SC Oncology GA CN7KL UT WOS:000358613202063 ER PT J AU Somlo, G Frankel, PH Luu, TH Ma, C Arun, B Garcia, A Cigler, T Cream, L Harvey, HA Sparano, JA Nanda, R Chew, HK Moynihan, TJ Vandat, LT Goetz, MP Hurria, A Mortimer, JE Gandara, DR Chen, A Weitzel, JN AF Somlo, George Frankel, Paul Henry Luu, Thehang H. Ma, Cynthia Arun, Banu Garcia, Agustin Cigler, Tessa Cream, Leah Harvey, Harold A. Sparano, Joseph A. Nanda, Rita Chew, Helen K. Moynihan, Timothy Jerome Vandat, Linda T. Goetz, Matthew P. Hurria, Arti Mortimer, Joanne E. Gandara, David R. Chen, Alice Weitzel, Jeffrey N. TI Phase II trial of single agent PARP inhibitor ABT-888 (veliparib [vel]) followed by postprogression therapy of vel with carboplatin (carb) in patients (pts) with stage BRCA-associated metastatic breast cancer (MBC): California Cancer Consortium trial PHII-96 SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT 50th Annual Meeting of the American-Society-of-Clinical-Oncology CY MAY 30-JUN 03, 2014 CL Chicago, IL SP Amer Soc Clin Oncol C1 City Hope Natl Med Ctr, Duarte, CA USA. City Hope Beckman Res Inst, Duarte, CA USA. City Hope Canc Ctr, Beckman Res Inst, Duarte, CA USA. Washington Univ, Sch Med, St Louis, MO USA. Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA. Univ So Calif, Los Angeles, CA USA. Weill Cornell Med Coll, New York, NY USA. Penn State MS Hershey Med Ctr, Hershey, PA USA. Hematol Oncol Div, Hershey, PA USA. Penn State Hershey Canc Inst, Hershey, PA USA. Montefiore Med Ctr, Bronx, NY 10467 USA. Univ Chicago, Chicago, IL 60637 USA. Univ Calif Davis, Sacramento, CA 95817 USA. Mayo Clin, Rochester, MN USA. UC Davis Comprehens Canc Ctr, Sacramento, CA USA. NCI, Rockville, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X EI 1527-7755 J9 J CLIN ONCOL JI J. Clin. Oncol. PD MAY 20 PY 2014 VL 32 IS 15 SU S MA 1021 PG 1 WC Oncology SC Oncology GA CN7KL UT WOS:000358613202443 ER PT J AU Spigel, DR Cereda, R Litten, JB Allen, AR Glaccone, G Socinski, MA Camidge, DR Besse, B AF Spigel, David R. Cereda, Roberta Litten, Jason B. Allen, Andrew R. Glaccone, Giuseppe Socinski, Mark A. Camidge, D. Ross Besse, Benjamin TI A single arm, open-label, phase II study to assess the efficacy of locitanib in patients with FGFR1-amplified surmounts NSCLC (sqNSCLC) SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT 50th Annual Meeting of the American-Society-of-Clinical-Oncology CY MAY 30-JUN 03, 2014 CL Chicago, IL SP Amer Soc Clin Oncol C1 Sarah Cannon Res Inst, Nashville, TN USA. EOS SpA, Milan, Italy. Clovis Oncol Inc, San Francisco, CA USA. Georgetown Univ, Washington, DC USA. NCI, Bethesda, MD 20892 USA. Univ Pittsburgh Med Ctr UPMC Canc Pavil, Pittsburgh, PA USA. Univ Colorado, Ctr Canc, Aurora, CO USA. Gustave Roussy, Villejuif, France. NR 0 TC 0 Z9 0 U1 0 U2 0 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 MAY 20 PY 2014 VL 32 IS 15 SU S MA TPS8119 PG 1 WC Oncology SC Oncology GA CN7KL UT WOS:000358613202199 ER PT J AU Stevens, PL Lenihan, DJ Ky, B Warneke, CL Johnson, MM Abramson, VG Mayer, IA Adams, PT Campbell, MG Cheema, PS Moore, DF Yeshwant, C Carver, JR Fisch, M AF Stevens, Patrick Lawson Lenihan, Daniel John Ky, Bonnie Warneke, Carla L. Johnson, Marcy M. Abramson, Vandana Gupta Mayer, Ingrid A. Adams, Paul T. Campbell, Mark G. Cheema, Puneet S. Moore, Dennis Frederic Yeshwant, Chilakamarri Carver, Joseph R. Fisch, Michael TI Prediction and early detection of anthracycline-related cardiotoxicity using cardiac biomarkers. SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT 50th Annual Meeting of the American-Society-of-Clinical-Oncology CY MAY 30-JUN 03, 2014 CL Chicago, IL SP Amer Soc Clin Oncol C1 Vanderbilt Univ, Med Ctr, Nashville, TN USA. Vanderbilt Univ, Nashville, TN 37235 USA. Univ Penn, Philadelphia, PA 19104 USA. Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA. Vanderbilt Univ, Sch Med, Vanderbilt Ingram Canc Ctr, Nashville, TN 37212 USA. Genesys Reg Med Ctr, Natl Surg Adjuvant Breast & Bowel Project, Flint, MI USA. Canc & Hem Ctr Western Michigan PC, Grand Rapids, MI USA. Healtheast Care, St Paul, MN USA. Canc Ctr Kansas, Wichita, KS USA. Cent Illinois CCOP, Springfield, IL USA. Hosp Univ Penn, Philadelphia, PA 19104 USA. NR 0 TC 1 Z9 1 U1 1 U2 1 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X EI 1527-7755 J9 J CLIN ONCOL JI J. Clin. Oncol. PD MAY 20 PY 2014 VL 32 IS 15 SU S MA 9644 PG 1 WC Oncology SC Oncology GA CN7KL UT WOS:000358613204528 ER PT J AU Swartz, C Recio, L Phillips, S Maynor, T Flgg, WD AF Swartz, Carol Recio, Leslie Phillips, Suzanne Maynor, Timothy Flgg, William Douglas TI Development of a CYP1B1*3 genotyping assay and mechanism of action studies related to docetaxel treatment in CRPC. SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT 50th Annual Meeting of the American-Society-of-Clinical-Oncology CY MAY 30-JUN 03, 2014 CL Chicago, IL SP Amer Soc Clin Oncol C1 Integrated Syst Lab, Res Triangle Pk, NC USA. NCI, Mol Pharmacol Sect, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 MAY 20 PY 2014 VL 32 IS 15 SU S MA e16036 PG 1 WC Oncology SC Oncology GA CN7KL UT WOS:000358613200792 ER PT J AU Tawbi, HAH Chu, E Lin, Y Hyman, DM Goel, S Rudek, MA Dowlati, A LoRusso, P Mulkerin, D Chew, HK Kiesel, B Pollice, L Appleman, LJ Puhalla, S Stoller, RG Lee, JJ Ivy, P Beumer, JH AF Tawbi, Hussein Abdul-Hassan Chu, Edward Lin, Yan Hyman, David Michael Goel, Sanjay Rudek, Michelle A. Dowlati, Afshin LoRusso, Patricia Mulkerin, Daniel Chew, Helen K. Kiesel, Brian Pollice, Laura Appleman, Leonard Joseph Puhalla, Shannon Stoller, Ronald G. Lee, James J. Ivy, Percy Beumer, Jan H. CA NCI-Organ Dysfunction Working Grp TI Early phase I study of the PARP inhibitor veliparib (ART-888) alone or in combination with carboplatia/paclitaxel (CP) in patients with varying degrees of hepatic or renal dysfunction: A study of the NCI-Organ Dysfunction Working Group (ODG). SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT 50th Annual Meeting of the American-Society-of-Clinical-Oncology CY MAY 30-JUN 03, 2014 CL Chicago, IL SP Amer Soc Clin Oncol C1 Univ Pittsburgh, Inst Canc, Pittsburgh, PA USA. Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. Albert Einstein Canc Ctr, New York, NY USA. Johns Hopkins, Sidney Kimmel Comprehens Canc Ctr, Baltimore, MD USA. Case Western Reserve Univ, Univ Hosp Seidman Canc Ctr, Case Comprehens Canc Ctr, Cleveland, OH 44106 USA. Wayne State Univ, Karmanos Canc Inst, Detroit, MI USA. Univ Wisconsin Hosp & Clin, Madison, WI 53792 USA. Univ Calif Davis, Sacramento, CA 95817 USA. Univ Pittsburgh, Ctr Canc, Med Ctr, Pittsburgh, PA USA. Univ Pittsburgh, Med Ctr, Pittsburgh, PA USA. Univ Pittsburgh, Magee Womens Hosp, Med Ctr, Womens Canc Program, Pittsburgh, PA 15213 USA. NCI, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 MAY 20 PY 2014 VL 32 IS 15 SU S MA 2572 PG 1 WC Oncology SC Oncology GA CN7KL UT WOS:000358613202837 ER PT J AU Thomas, A Rajan, A Berman, AW Brzezniak, CE Spittler, AJ Carter, CA Guha, U Wang, Y Szabo, E Loehrer, PJ Giaccone, G AF Thomas, Anish Rajan, Arun Berman, Arlene W. Brzezniak, Christina E. Spittler, Aaron John Carter, Corey Allan Guha, Udayan Wang, Yisong Szabo, Eva Loehrer, Patrick J. Giaccone, Giuseppe TI Phase II trial of sunitinib in patients with thymic epithelial tumors (TET). SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT 50th Annual Meeting of the American-Society-of-Clinical-Oncology CY MAY 30-JUN 03, 2014 CL Chicago, IL SP Amer Soc Clin Oncol C1 NCI, NIH, Bethesda, MD 20892 USA. Walter Reed Natl Mil Med Ctr, Bethesda, MD USA. Indiana Univ, Melvin & Bren Simon Canc Ctr, Indianapolis, IN 46204 USA. NCI, Bethesda, MD 20892 USA. Georgetown Univ, Washington, DC USA. NR 0 TC 4 Z9 4 U1 0 U2 0 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 MAY 20 PY 2014 VL 32 IS 15 SU S MA 7525 PG 1 WC Oncology SC Oncology GA CN7KL UT WOS:000358613203961 ER PT J AU Tolaney, SM Guo, H Barry, WT Larrabee, K Brock, JE Wagle, N Van Allen, EM Paweletz, C Ivanova, E Janne, PA Overmoyer, B Wright, JJ Shapiro, G Winer, EP Krop, IE AF Tolaney, Sara M. Guo, Hao Barry, William Thomas Larrabee, Katherine Brock, Jane E. Wagle, Nikhil Van Allen, Eliezer Mendel Paweletz, Cloud Ivanova, Elena Janne, Pasi A. Overmoyer, Beth Wright, John Joseph Shapiro, Geoffrey Winer, Eric P. Krop, Ian E. TI A phase II study of tivantinib (ARQ-197) for metastatic triple-negative breast cancer. SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT 50th Annual Meeting of the American-Society-of-Clinical-Oncology CY MAY 30-JUN 03, 2014 CL Chicago, IL SP Amer Soc Clin Oncol C1 Dana Farber Canc Inst, Boston, MA 02115 USA. Dana Farber Canc Inst, Belfer Inst Appl Canc Sci, Boston, MA USA. NCI, Rockville, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 MAY 20 PY 2014 VL 32 IS 15 SU S MA 1106 PG 1 WC Oncology SC Oncology GA CN7KL UT WOS:000358613202526 ER PT J AU Ulahannan, SV Rahma, OE Liewehr, DJ Steinberg, SM Duffy, AG AF Ulahannan, Susanna V. Rahma, Osama E. Liewehr, David J. Steinberg, Seth M. Duffy, Austin G. TI Systemic chemotherapy for the treatment of advanced biliary tract carcinoma (BTC). SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT 50th Annual Meeting of the American-Society-of-Clinical-Oncology CY MAY 30-JUN 03, 2014 CL Chicago, IL SP Amer Soc Clin Oncol C1 NCI, NIH, Bethesda, MD 20892 USA. NIH, Bethesda, MD 20892 USA. NCI, Biostat & Data Management Sect, Ctr Canc Res, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X EI 1527-7755 J9 J CLIN ONCOL JI J. Clin. Oncol. PD MAY 20 PY 2014 VL 32 IS 15 SU S MA e15129 PG 1 WC Oncology SC Oncology GA CN7KL UT WOS:000358613200528 ER PT J AU Varticovski, L Kim, S Nickerson, M Grontved, L Lao, QZ Thompson, B Theodorescu, D Hager, G AF Varticovski, Lyuba Kim, Sohyoung Nickerson, Michael Grontved, Lars Lao, Qizong Thompson, Bethtrice Theodorescu, Dan Hager, Gordon TI Bladder cancer global unbiased chromatin landscape characterization by DHS-seq to identify novel features unique for each stage of progression SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT 50th Annual Meeting of the American-Society-of-Clinical-Oncology CY MAY 30-JUN 03, 2014 CL Chicago, IL SP Amer Soc Clin Oncol C1 NCI, Ctr Clin, NIH, Bethesda, MD 20892 USA. NCI, Bethesda, MD 20892 USA. NCI, Frederick, MD 21701 USA. Univ Southern Denmark, Odense, Denmark. Howard Univ, Washington, DC 20059 USA. Univ Virginia, Charlottesville, VA USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X EI 1527-7755 J9 J CLIN ONCOL JI J. Clin. Oncol. PD MAY 20 PY 2014 VL 32 IS 15 SU S MA e15500 PG 1 WC Oncology SC Oncology GA CN7KL UT WOS:000358613200650 ER PT J AU von Mehren, M George, S Heinrich, MC Schuetze, S Belinsky, MG Janeway, KA Rink, L Ganjoo, KN Yu, JQ Yap, JT Wright, JJ Van den Abbeele, AD AF von Mehren, Margaret George, Suzanne Heinrich, Michael C. Schuetze, Scott Belinsky, Martin G. Janeway, Katherine A. Rink, Lori Ganjoo, Kristen N. Yu, Jian Qin Yap, Jeffrey T. Wright, John Joseph Van den Abbeele, Annick D. TI Results of SARC 022, a phase II multicenter study of linsitinib in pediatric and adult wild-type (WT) gastrointestinal stromal tumors (GIST). SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT 50th Annual Meeting of the American-Society-of-Clinical-Oncology CY MAY 30-JUN 03, 2014 CL Chicago, IL SP Amer Soc Clin Oncol C1 Fox Chase Canc Ctr, Philadelphia, PA 19111 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. OHSU Knight Canc Inst, Portland, OR USA. Portland VA Med Ctr, Portland, OR USA. Univ Michigan, Ann Arbor, MI 48109 USA. Stanford Univ, Palo Alto, CA 94304 USA. Huntsman Canc Inst, Salt Lake City, UT USA. NCI, Rockville, MD USA. NR 0 TC 1 Z9 1 U1 3 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 MAY 20 PY 2014 VL 32 IS 15 SU S MA 10507 PG 1 WC Oncology SC Oncology GA CN7KL UT WOS:000358613204640 ER PT J AU Von Minckwitz, G O'Shaughnessy, J Winer, EP Wolmark, N Geyer, CE Huober, JB Loibl, S Sikov, WM Untch, M McKee, MD Giranda, VL Rugo, HS AF Von Minckwitz, Gunter O'Shaughnessy, Joyce Winer, Eric P. Wolmark, Norman Geyer, Charles E. Huober, Jens Bodo Loibl, Sibylle Sikov, William M. Untch, Michael McKee, Mark D. Giranda, Vincent L. Rugo, Hope S. TI Phase III study evaluating safety and efficacy of the addition of veliparib plus carboplatin versus the addition of carboplatin to standard neoadjuvant chemotherapy in subjects with early-stage triple-negative breast cancer (TNBC). SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT 50th Annual Meeting of the American-Society-of-Clinical-Oncology CY MAY 30-JUN 03, 2014 CL Chicago, IL SP Amer Soc Clin Oncol C1 Goethe Univ Frankfurt, German Breast Grp, D-60054 Frankfurt, Germany. Baylor Charles A Sammons Canc Ctr, Texas Oncol, Dallas, TX USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Natl Surg Adjuvant Breast & Bowel Project, Pittsburgh, PA USA. Virginia Commonwealth Univ, Sch Med, Richmond, VA USA. Univ Ulm, D-89069 Ulm, Germany. Sana Klinikum Offenbach, German Breast Grp, Neu Isenburg, Germany. Brown Univ, Alpert Med Sch, Providence, RI 02912 USA. Helios Klinikum Berlin Buch, Berlin, Germany. AbbVie Inc, N Chicago, IL USA. UCSF Helen Diller Family Comprehens Canc Ctr, San Francisco, CA USA. NR 0 TC 1 Z9 1 U1 2 U2 2 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 MAY 20 PY 2014 VL 32 IS 15 SU S MA TPS1149 PG 1 WC Oncology SC Oncology GA CN7KL UT WOS:000358613202012 ER PT J AU Wagner, LM Fouladi, M Ahmed, A Krailo, MD Weigel, B DuBois, SG Doyle, A Chen, HX Blaney, S AF Wagner, Lars M. Fouladi, Maryam Ahmed, Atif Krailo, Mark D. Weigel, Brenda DuBois, Steven G. Doyle, Austin Chen, Helen X. Blaney, Susan TI Phase II trial of cixutumumab in combination with temsirolimus in pediatric patients with recurrent or refractory sarcoma: A report from the Children's Oncology Group. SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT 50th Annual Meeting of the American-Society-of-Clinical-Oncology CY MAY 30-JUN 03, 2014 CL Chicago, IL SP Amer Soc Clin Oncol C1 Univ Kentucky, Lexington, KY USA. Cincinnati Childrens Hosp Med Ctr, Cincinnati, OH 45229 USA. Childrens Mercy Hosp & Clin, Kansas City, MO USA. Childrens Oncol Grp, Arcadia, CA USA. Univ Minnesota, Minneapolis, MN USA. Univ Calif San Francisco, San Francisco, CA 94143 USA. NCI, Rockville, MD USA. NCI, Canc Therapy Evaluat Program, Rockville, MD USA. Texas Childrens Canc Ctr, Houston, TX USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 MAY 20 PY 2014 VL 32 IS 15 SU S MA 10066 PG 1 WC Oncology SC Oncology GA CN7KL UT WOS:000358613204605 ER PT J AU Wan, X Yeung, C Heske, C Mendoza, A Helman, LJ AF Wan, Xiaolin Yeung, Choh Heske, Christine Mendoza, Arnulfo Helman, Lee J. TI IGF-IR inhibition effect on a yes/SFK bypass resistance pathway: Rational basis for cotargeting IGF-IR and yes/SFK kinase in rhabdomyosarcoma. SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT 50th Annual Meeting of the American-Society-of-Clinical-Oncology CY MAY 30-JUN 03, 2014 CL Chicago, IL SP Amer Soc Clin Oncol C1 NCI, Pediat Oncol, CCR, NIH, Bethesda, MD 20892 USA. NCI, Pediat Oncol Branch, Bethesda, MD 20892 USA. NCI, NIH, Bethesda, MD 20892 USA. NCI, Ctr Canc Res, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 MAY 20 PY 2014 VL 32 IS 15 SU S MA 10045 PG 1 WC Oncology SC Oncology GA CN7KL UT WOS:000358613204584 ER PT J AU Wang, YS Meltzer, PS Lau, C Thomas, A Rajan, A Giaccone, G AF Wang, Yisong Meltzer, Paul S. Lau, Christopher Thomas, Anish Rajan, Arun Giaccone, Giuseppe TI Recurrence of epigenetic gene mutations in thymic epithelial carcinomas revealed by targeted exome sequencing of cancer-associated genes. SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT 50th Annual Meeting of the American-Society-of-Clinical-Oncology CY MAY 30-JUN 03, 2014 CL Chicago, IL SP Amer Soc Clin Oncol C1 Georgetown Univ, Washington, DC USA. NCI, Bethesda, MD 20892 USA. NCI, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 MAY 20 PY 2014 VL 32 IS 15 SU S MA 7529 PG 1 WC Oncology SC Oncology GA CN7KL UT WOS:000358613203965 ER PT J AU Weekes, CD Lamberts, LE Borad, MJ Voortman, J McWilliams, RR Diamond, JR De Vries, E Verheul, HMW Lieu, CH Yue, HB Wang, YL Scales, S Samineni, D Wood, K Brunstein, F Maslyar, DJ Kim, GP AF Weekes, Colin D. Lamberts, Laetitia E. Borad, Mitesh J. Voortman, Johannes McWilliams, Robert R. Diamond, Jennifer Robinson De Vries, Elisabeth Verheul, Henk M. W. Lieu, Christopher Hanyoung Yue, Huibin Wang, Yulei Scales, Suzie Samineni, Divya Wood, Katie Brunstein, Flavia Maslyar, Daniel J. Kim, George P. TI A phase I study of DMOT4039A, an antibody-drug conjugate (ADC) targeting mesothelin (MSLN), in patients (pts) with unresectable pancreatic (PC) or piatinum-resistant ovarian cancer (OC) SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT 50th Annual Meeting of the American-Society-of-Clinical-Oncology CY MAY 30-JUN 03, 2014 CL Chicago, IL SP Amer Soc Clin Oncol C1 Univ Colorado, Ctr Canc, Aurora, CO USA. Univ Med Ctr Groningen, Dept Med Oncol, NL-9713 AV Groningen, Netherlands. Mayo Clin, Scottsdale, AZ USA. NCI, Med Oncol Branch, Bethesda, MD 20892 USA. Mayo Clin, Rochester, MN USA. Univ Colorado Denver, Div Med Oncol, Aurora, CO USA. Univ Med Ctr Groningen, NL-9713 AV Groningen, Netherlands. Vrije Univ Amsterdam, Med Ctr, Dept Med Oncol, Amsterdam, Netherlands. Univ Colorado, Denver, CO 80202 USA. Genentech Inc, San Francisco, CA USA. Genentech Inc, San Francisco, CA 94080 USA. Mayo Clin, Jacksonville, FL 32224 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 MAY 20 PY 2014 VL 32 IS 15 SU S MA 2529 PG 1 WC Oncology SC Oncology GA CN7KL UT WOS:000358613202794 ER PT J AU Weinstein, JN Kim, J Creighton, CJ Akbani, R Hoadley, KA Kim, WY Morgan, MB Hinoue, T Rosenberg, JE Bajorin, DF Hansel, DE Al-Ahmadie, H Gordenin, D Stuart, JM Robertson, G Kucherlapati, R Laird, PW Mills, GB Kwiatkowski, DJ Lerner, SP AF Weinstein, John N. Kim, Jaegil Creighton, Chad J. Akbani, Rehan Hoadley, Katherine A. Kim, William Y. Morgan, Margaret B. Hinoue, Toshinori Rosenberg, Jonathan E. Bajorin, Dean F. Hansel, Donna E. Al-Ahmadie, Hikmat Gordenin, Dmitry Stuart, Joshua M. Robertson, Gordon Kucherlapati, Raju Laird, Peter W. Mills, Gordon B. Kwiatkowski, David J. Lerner, Seth P. CA Canc Genome Atlas Bladder Canc TI Comprehensive molecular profiling of urothelial bladder cancer at the DNA, RNA, and protein levels: A TCGA project. SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT 50th Annual Meeting of the American-Society-of-Clinical-Oncology CY MAY 30-JUN 03, 2014 CL Chicago, IL SP Amer Soc Clin Oncol C1 Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA. Broad Inst Harvard & MIT, Cambridge, MA USA. Baylor Coll Med, Houston, TX 77030 USA. Univ N Carolina, Chapel Hill, NC USA. Univ So Calif, Los Angeles, CA USA. Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. Cleveland Clin, Cleveland, OH 44106 USA. NIEHS, Res Triangle Pk, NC 27709 USA. Univ Calif Santa Cruz, Dept Biomol Engn, Santa Cruz, CA 95064 USA. BC Canc Agcy, Vancouver, BC, Canada. Harvard Univ, Sch Med, Boston, MA USA. USC Norris Comprehens Canc Ctr, Los Angeles, CA USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Baylor Coll Med, Scott Dept Urol, Houston, TX 77030 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 MAY 20 PY 2014 VL 32 IS 15 SU S MA 4509 PG 1 WC Oncology SC Oncology GA CN7KL UT WOS:000358613203314 ER PT J AU Widemann, BC Schwartz, S Thomas, E Chauhan, N King, T Howard, SC AF Widemann, Brigitte C. Schwartz, Stefan Thomas, Emma Chauhan, Nikhil King, Thomas Howard, Scott C. TI Immunogenicity and safety of glucarpidase for methotrexate toxicity. SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT 50th Annual Meeting of the American-Society-of-Clinical-Oncology CY MAY 30-JUN 03, 2014 CL Chicago, IL SP Amer Soc Clin Oncol C1 NCI, Pediat Oncol Branch, NIH, Bethesda, MD 20892 USA. Charite, D-13353 Berlin, Germany. BTG, London, England. BTG Int Inc, London, PA, England. BTG Int Inc, W Conshohocken, PA USA. St Jude Childrens Res Hosp, Memphis, TN 38105 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X EI 1527-7755 J9 J CLIN ONCOL JI J. Clin. Oncol. PD MAY 20 PY 2014 VL 32 IS 15 SU S MA e20648 PG 1 WC Oncology SC Oncology GA CN7KL UT WOS:000358613201621 ER PT J AU Widemann, BC Marcus, LJ Fisher, MJ Weiss, BD Kim, A Dombi, E Baldwin, A Whitcomb, P Martin, S Gillespie, A Doyle, A AF Widemann, Brigitte C. Marcus, Leigh Jessica Fisher, Michael J. Weiss, Brian D. Kim, AeRang Dombi, Eva Baldwin, Andrea Whitcomb, Patricia Martin, Staci Gillespie, Andrea Doyle, Austin TI Phase 1 study of the MEK1/2 inhibitor selumetinib (AZD6244) hydrogen sulfate in children and young adults with neurofibromatosis type 1 (NF1) and inoperable plexiform neurofibromas (PNs). SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT 50th Annual Meeting of the American-Society-of-Clinical-Oncology CY MAY 30-JUN 03, 2014 CL Chicago, IL SP Amer Soc Clin Oncol C1 NCI, Pediat Oncol Branch, NIH, Bethesda, MD 20892 USA. Childrens Natl Med Ctr, Washington, DC 20010 USA. Childrens Hosp, Philadelphia, PA 19104 USA. Cincinnati Childrens Hosp Med Ctr, Cincinnati, OH 45229 USA. NCI, Bethesda, MD 20892 USA. NCI, Rockville, MD USA. NR 0 TC 10 Z9 10 U1 0 U2 2 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 MAY 20 PY 2014 VL 32 IS 15 SU S MA 10018 PG 1 WC Oncology SC Oncology GA CN7KL UT WOS:000358613204557 ER PT J AU Wigle, DA Mandrekar, SJ Allen-Ziegler, K Gesthalter, Y Holland, P Aubry, MC Limburg, PJ Avi, S Szabo, E AF Wigle, Dennis A. Mandrekar, Sumithra J. Allen-Ziegler, Katie Gesthalter, Yaron Holland, Paul Aubry, Marie-Christine Limburg, Paul J. Avi, Spira Szabo, Eva TI Pioglitazone as a candidate chemoprevention agent for lung cancer: A pilot window trial in early stage NSCLC. SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT 50th Annual Meeting of the American-Society-of-Clinical-Oncology CY MAY 30-JUN 03, 2014 CL Chicago, IL SP Amer Soc Clin Oncol C1 Mayo Clin, Rochester, MN USA. Boston Univ, Sch Med, Boston, MA 02118 USA. NCI, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X EI 1527-7755 J9 J CLIN ONCOL JI J. Clin. Oncol. PD MAY 20 PY 2014 VL 32 IS 15 SU S MA 1581 PG 1 WC Oncology SC Oncology GA CN7KL UT WOS:000358613202632 ER PT J AU Wilson, M Dhani, NC Hirte, HW Welch, S Steed, H Martin, LP Lheureux, S Martin-Lorente, C Mackay, H Butler, MO Wang, L Quintos, J Allen, K Roman, L Wright, JJ Oza, AM AF Wilson, Michelle Dhani, Neesha C. Hirte, Hai W. Welch, Stephen Steed, Helen Martin, Lalnie P. Lheureux, Stephanie Martin-Lorente, Cristina Mackay, Helen Butler, Marcus O. Wang, Lisa Quintos, Judy Allen, Katie Roman, Lynda Wright, John Joseph Oza, Amit M. TI Phase II study of XL184 (cabozantinib) in recurrent or metastatic endometrial cancer: A trial or the PMH, Chicago, and California Phase II Consortia SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT 50th Annual Meeting of the American-Society-of-Clinical-Oncology CY MAY 30-JUN 03, 2014 CL Chicago, IL SP Amer Soc Clin Oncol C1 Princess Margaret Canc Ctr, Dept Oncol, Toronto, ON, Canada. Univ Toronto, Princess Margaret Canc Ctr, Univ Hlth Network, Div Med Oncol & Hematol,Dept Med, Toronto, ON, Canada. Juravinski Canc Ctr, Hamilton, ON, Canada. London Reg Canc Program, London, ON, Canada. Cross Canc Inst, Edmonton, AB T6G 1Z2, Canada. Fox Chase Canc Ctr, Philadelphia, PA 19111 USA. Princess Margaret Canc Ctr, Toronto, ON, Canada. Univ Hlth Network, Princess Margaret Canc Ctr, Toronto, ON, Canada. Princess Margaret Canc Ctr, Dept Biostat, Toronto, ON, Canada. Princess Margaret Hosp, Toronto, ON M4X 1K9, Canada. USC Norris Comprehens Canc Ctr, Los Angeles, CA USA. NCI, Rockville, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 MAY 20 PY 2014 VL 32 IS 15 SU S MA TPS5629 PG 1 WC Oncology SC Oncology GA CN7KL UT WOS:000358613202167 ER PT J AU Wolmark, N Mamounas, EP Baehner, FL Butler, SM Tang, G Jamshidian, F Sing, AP Shak, S Paik, S AF Wolmark, Norman Mamounas, Eleftherios P. Baehner, Frederick L. Butler, Steven M. Tang, Gong Jamshidian, Farid Sing, Amy P. Shak, Steven Paik, Soonmyung TI Recurrence score and quantitative ER expression to predict in late distant recurrence risk in ER+ BC after 5 years of tamoxifen. SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT 50th Annual Meeting of the American-Society-of-Clinical-Oncology CY MAY 30-JUN 03, 2014 CL Chicago, IL SP Amer Soc Clin Oncol C1 Allegheny Gen Hosp, Allegheny Canc Ctr, Natl Surg Adjuvant Breast & Bowel Project, Pittsburgh, PA 15212 USA. NSABP, Orlando, FL USA. UF Hlth Canc Ctr, Orlando Hlth, Orlando, FL USA. Genomic Hlth Inc, Redwood City, CA USA. NSABP Biostat Ctr, Pittsburgh, PA USA. Univ Pittsburgh, Grad Sch Publ Hlth, Pittsburgh, PA USA. Yonsei Univ, Coll Med, NSABP, Pittsburgh, PA USA. Yonsei Univ, Coll Med, Severance Biomed Sci Inst, Pittsburgh, PA USA. Yonsei Univ, Coll Med, Dept Med Oncol, Pittsburgh, PA USA. NR 0 TC 0 Z9 0 U1 3 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 MAY 20 PY 2014 VL 32 IS 15 SU S MA 11024 PG 1 WC Oncology SC Oncology GA CN7KL UT WOS:000358613204757 ER PT J AU Wong, JR Morton, LM Tucker, MA Abramson, DH Seddon, J Sampson, J Kleinerman, R AF Wong, Jeannette R. Morton, Lindsay M. Tucker, Margaret A. Abramson, David H. Seddon, Johanna Sampson, Joshua Kleinerman, Ruth TI Risk of subsequent malignant neoplasms in long-term retinoblastoma survivors following chemotherapy and radiotherapy. SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT 50th Annual Meeting of the American-Society-of-Clinical-Oncology CY MAY 30-JUN 03, 2014 CL Chicago, IL SP Amer Soc Clin Oncol C1 NCI, Rockville, MD USA. NCI, Bethesda, MD 20892 USA. NIH, Bethesda, MD 20892 USA. Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X EI 1527-7755 J9 J CLIN ONCOL JI J. Clin. Oncol. PD MAY 20 PY 2014 VL 32 IS 15 SU S MA 10079 PG 1 WC Oncology SC Oncology GA CN7KL UT WOS:000358613204618 ER PT J AU Wright, M AF Wright, Matthew TI Safety of percutaneous, image guided biopsy in a series of children and young adults with pediatric sarcomas SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT 50th Annual Meeting of the American-Society-of-Clinical-Oncology CY MAY 30-JUN 03, 2014 CL Chicago, IL SP Amer Soc Clin Oncol C1 [Wright, Matthew] NCI, NIH, Rockville, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 MAY 20 PY 2014 VL 32 IS 15 SU S MA e21026 PG 1 WC Oncology SC Oncology GA CN7KL UT WOS:000358613201717 ER PT J AU Yang, SX Rubinstein, L Nguyen, D Tomaszewski, JE Takebe, N Ivy, P Doroshow, JH AF Yang, Sherry X. Rubinstein, Larry Dat Nguyen Tomaszewski, Joseph E. Takebe, Naoko Ivy, Percy Doroshow, James H. TI Association of Notch-1 phenotype with clinical stage progression in non-small cell lung cancer SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT 50th Annual Meeting of the American-Society-of-Clinical-Oncology CY MAY 30-JUN 03, 2014 CL Chicago, IL SP Amer Soc Clin Oncol C1 NCI, Div Canc Treatment & Diag, Bethesda, MD 20892 USA. Div Canc Treatment & Diag, Bethesda, MD USA. NCI, Bethesda, MD 20892 USA. Canc Therapy Evaluat Program, Invest Drug Branch, Rockville, MD USA. NR 0 TC 3 Z9 3 U1 0 U2 0 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 MAY 20 PY 2014 VL 32 IS 15 SU S MA e22123 PG 1 WC Oncology SC Oncology GA CN7KL UT WOS:000358613201852 ER PT J AU Yothers, G George, TJ Petrelli, NJ O'Connell, MJ Beart, RW Allegra, CJ Roh, MS Lopa, SH Colangelo, LH Sharif, S Wolmark, N AF Yothers, Greg George, Thomas J. Petrelli, Nicholas J. O'Connell, Michael J. Beart, Robert W. Allegra, Carmen Joseph Roh, Mark S. Lopa, Samia H. Colangelo, Linda H. Sharif, Saima Wolmark, Norman TI Neoadjuvant rectal cancer (RC) score to predict survival: Potential surrogate endpoint for early phase trials. SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT 50th Annual Meeting of the American-Society-of-Clinical-Oncology CY MAY 30-JUN 03, 2014 CL Chicago, IL SP Amer Soc Clin Oncol C1 Natl Surg Adjuvant Breast & Bowel Project Biostat, Pittsburgh, PA USA. Univ Pittsburgh, Grad Sch Publ Hlth, Dept Biostat, Pittsburgh, PA 15261 USA. NSABP, Gainesville, FL USA. Univ Florida, Gainesville, FL USA. NSABP, Newark, DE USA. Helen F Graham Canc Ctr & Res Inst, Newark, DE USA. NSABP, Pittsburgh, PA USA. NSABP, Glendale, CA USA. Glendale Mem Hosp, Glendale, CA USA. NSABP, Orlando, FL USA. UF Hlth Canc Ctr Orlando Hlth, Orlando, FL USA. NSABP Biostat Ctr, Pittsburgh, PA USA. Allegheny Gen Hosp, Allegheny Canc Ctr, Pittsburgh, PA 15212 USA. NR 0 TC 1 Z9 1 U1 0 U2 0 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 MAY 20 PY 2014 VL 32 IS 15 SU S MA 3533 PG 1 WC Oncology SC Oncology GA CN7KL UT WOS:000358613203049 ER PT J AU Younes, A Zinzani, PL Sehn, LH Johnson, PWM Gascoyne, RD Ahmedi, T Bellew, KM Verrneulen, J Zhuang, SH Zhuang Staudt, LM Wilson, WH AF Younes, Anas Zinzani, Pier Luigi Sehn, Laurie Helen Johnson, Peter W. M. Gascoyne, Randy D. Ahmedi, Tahamtan Bellew, Kevin M. Verrneulen, Jessica Zhuang, Sen Hong Sun, Stevan Staudt, Louis M. Wilson, Wyndham Hopkins TI A randomized, double-blind, placebo-controlled phase 3 study of ibrutinib in combination with rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) us subjects with newly diagnosed nongerminal center B-cell subtype of diffuse large B-cell lymphoma (DLBCL) SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT 50th Annual Meeting of the American-Society-of-Clinical-Oncology CY MAY 30-JUN 03, 2014 CL Chicago, IL SP Amer Soc Clin Oncol C1 Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. Univ Bologna, Inst Hematol & Med Oncol, Bologna, Italy. British Columbia Canc Agcy, Ctr Lymphoid Canc, Div Med Oncol, Vancouver, BC V5Z 4E6, Canada. Univ British Columbia, Vancouver, BC V5Z 1M9, Canada. Univ Southampton, Canc Res UK Ctr, Southampton, Hants, England. British Columbia Canc Agcy, Ctr Lymphoid Canc, Vancouver, BC V5Z 4E6, Canada. Janssen Res & Dev, Raritan, NJ USA. Janssen Res & Dev, Spring House, PA USA. Janssen Res & Dev, Leiden, Netherlands. NCI, Bethesda, MD 20892 USA. RI Zinzani, Pier Luigi/J-9182-2016 OI Zinzani, Pier Luigi/0000-0002-2112-2651 NR 0 TC 0 Z9 0 U1 0 U2 0 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 MAY 20 PY 2014 VL 32 IS 15 SU S MA TPS8615 PG 1 WC Oncology SC Oncology GA CN7KL UT WOS:000358613202217 ER PT J AU Zeidner, JF Foster, MC Blackford, A Litzow, MR Morris, L Strickland, SA Lancet, JE Bose, P Levy, MY Tibes, R Gojo, I Gocke, CD Rosner, GL Greer, J Cain, JM Little, RF Wright, JJ Doyle, LA Smith, BD Karp, JE AF Zeidner, Joshua F. Foster, Matthew C. Blackford, Amanda Litzow, Mark Robert Morris, Lawrence Strickland, Stephen Anthony Lancet, Jeffrey E. Bose, Prithviraj Levy, M. Yair Tibes, Raoul Gojo, Ivana Gocke, Christopher D. Rosner, Gary L. Greer, Jacqueline Cain, Joan M. Little, Richard F. Wright, John Joseph Doyle, L. Austin Smith, B. Douglas Karp, Judith E. TI Randomized multicenter phase II trial of timed-sequential therapy with flavopiridol (alvocidib), cytarabine, and mitoxantrone (FLAM) versus "7+3" for adults with newly diagnosed acute myeloid leukemia (AML). SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT 50th Annual Meeting of the American-Society-of-Clinical-Oncology CY MAY 30-JUN 03, 2014 CL Chicago, IL SP Amer Soc Clin Oncol C1 Johns Hopkins Univ Hosp, Baltimore, MD 21287 USA. Sidney Kimmel Comprehens Canc Ctr Johns Hopkins, Baltimore, MD USA. UNC Lineberger Comprehens Canc Ctr, Chapel Hill, NC USA. Mayo Clin, Rochester, MN USA. BMT Grp Georgia, Atlanta, GA USA. Vanderbilt Univ, Med Ctr, Nashville, TN 37235 USA. Univ S Florida, Coll Med, H Lee Moffitt Canc Ctr & Res Inst, Tampa, FL 33612 USA. VCU Masey Canc Ctr, Richmond, VA USA. Texas Oncol Baylor Charles Sammons Canc Ctr, Dallas, TX USA. Mayo Clin, Scottsdale, AZ USA. Natl Canc Inst, Rockville, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 MAY 20 PY 2014 VL 32 IS 15 SU S MA 7002 PG 1 WC Oncology SC Oncology GA CN7KL UT WOS:000358613203822 ER PT J AU Butler, CL Lucas, O Wuchty, S Xue, B Uversky, VN White, M AF Butler, Carrie L. Lucas, Olivier Wuchty, Stefan Xue, Bin Uversky, Vladimir N. White, Michael TI Identifying Novel Cell Cycle Proteins in Apicomplexa Parasites through Co-Expression Decision Analysis SO PLOS ONE LA English DT Article ID TOXOPLASMA-GONDII; PLASMODIUM-FALCIPARUM; FUNCTIONAL-ANALYSIS; INTRINSIC DISORDER; MALARIA; REVEALS; SEQUENCE; GENES; IDENTIFICATION; CYTOSKELETON AB Hypothetical proteins comprise roughly half of the predicted gene complement of Toxoplasma gondii and Plasmodium falciparum and represent the largest class of uniquely functioning proteins in these parasites. Following the idea that functional relationships can be informed by the timing of gene expression, we devised a strategy to identify the core set of apicomplexan cell division cycling genes with important roles in parasite division, which includes many uncharacterized proteins. We assembled an expanded list of orthologs from the T. gondii and P. falciparum genome sequences (2781 putative orthologs), compared their mRNA profiles during synchronous replication, and sorted the resulting set of dual cell cycle regulated orthologs (744 total) into protein pairs conserved across many eukaryotic families versus those unique to the Apicomplexa. The analysis identified more than 100 ortholog gene pairs with unknown function in T. gondii and P. falciparum that displayed co-conserved mRNA abundance, dynamics of cyclical expression and similar peak timing that spanned the complete division cycle in each parasite. The unknown cyclical mRNAs encoded a diverse set of proteins with a wide range of mass and showed a remarkable conservation in the internal organization of ordered versus disordered structural domains. A representative sample of cyclical unknown genes (16 total) was epitope tagged in T. gondii tachyzoites yielding the discovery of new protein constituents of the parasite inner membrane complex, key mitotic structures and invasion organelles. These results demonstrate the utility of using gene expression timing and dynamic profile to identify proteins with unique roles in Apicomplexa biology. C1 [Butler, Carrie L.; Lucas, Olivier; Xue, Bin; Uversky, Vladimir N.] Univ S Florida, Morsani Coll Med, Dept Mol Med, Tampa, FL USA. [White, Michael] Univ S Florida, Coll Publ Hlth, Dept Global Hlth, Tampa, FL 33620 USA. [White, Michael] Univ S Florida, Florida Ctr Drug Discovery & Innovat, Tampa, FL USA. [Wuchty, Stefan] NIH, Natl Ctr Biotechnol Informat, Bethesda, MD 20892 USA. RP White, M (reprint author), Univ S Florida, Coll Publ Hlth, Dept Global Hlth, Tampa, FL 33620 USA. EM mwhite.usf@gmail.com RI Uversky, Vladimir/F-4515-2011 OI Uversky, Vladimir/0000-0002-4037-5857 FU National Institutes of Health [R01-AI077662, R01-AI089885] FX This work was supported by grants from the National Institutes of Health to MWW (R01-AI077662 and R01-AI089885). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 66 TC 2 Z9 2 U1 0 U2 2 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA SN 1932-6203 J9 PLOS ONE JI PLoS One PD MAY 19 PY 2014 VL 9 IS 5 AR e97625 DI 10.1371/journal.pone.0097625 PG 16 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA AN9SK UT WOS:000340948600052 PM 24841368 ER PT J AU Krupovic, M Makarova, KS Forterre, P Prangishvili, D Koonin, EV AF Krupovic, Mart Makarova, Kira S. Forterre, Patrick Prangishvili, David Koonin, Eugene V. TI Casposons: a new superfamily of self-synthesizing DNA transposons at the origin of prokaryotic CRISPR-Cas immunity SO BMC BIOLOGY LA English DT Article DE Mobile genetic elements; CRISPR-Cas system; Adaptive immunity; Transposons; Archaea; DNA polymerases ID INSERTION SEQUENCES; ESCHERICHIA-COLI; GENOME SEQUENCE; EVOLUTION; PROTEIN; ELEMENTS; ARCHAEA; SYSTEMS; VIRUSES; EUKARYOTES AB Background: Diverse transposable elements are abundant in genomes of cellular organisms from all three domains of life. Although transposons are often regarded as junk DNA, a growing body of evidence indicates that they are behind some of the major evolutionary innovations. With the growth in the number and diversity of sequenced genomes, previously unnoticed mobile elements continue to be discovered. Results: We describe a new superfamily of archaeal and bacterial mobile elements which we denote casposons because they encode Cas1 endonuclease, a key enzyme of the CRISPR-Cas adaptive immunity systems of archaea and bacteria. The casposons share several features with self-synthesizing eukaryotic DNA transposons of the Polinton/Maverick class, including terminal inverted repeats and genes for B family DNA polymerases. However, unlike any other known mobile elements, the casposons are predicted to rely on Cas1 for integration and excision, via a mechanism similar to the integration of new spacers into CRISPR loci. We identify three distinct families of casposons that differ in their gene repertoires and evolutionary provenance of the DNA polymerases. Deep branching of the casposon-encoded endonuclease in the Cas1 phylogeny suggests that casposons played a pivotal role in the emergence of CRISPR-Cas immunity. Conclusions: The casposons are a novel superfamily of mobile elements, the first family of putative self-synthesizing transposons discovered in prokaryotes. The likely contribution of capsosons to the evolution of CRISPR-Cas parallels the involvement of the RAG1 transposase in vertebrate immunoglobulin gene rearrangement, suggesting that recruitment of endonucleases from mobile elements as ready-made tools for genome manipulation is a general route of evolution of adaptive immunity. C1 [Krupovic, Mart; Forterre, Patrick; Prangishvili, David] Inst Pasteur, Unit Biol Mol Gene Chez Extremophiles, F-75015 Paris, France. [Makarova, Kira S.; Koonin, Eugene V.] Natl Lib Med, Natl Ctr Biotechnol Informat, Bethesda, MD 20894 USA. RP Krupovic, M (reprint author), Inst Pasteur, Unit Biol Mol Gene Chez Extremophiles, 25 Rue Docteur Roux, F-75015 Paris, France. EM krupovic@pasteur.fr; koonin@ncbi.nlm.nih.gov RI Krupovic, Mart/I-4209-2012 OI Krupovic, Mart/0000-0001-5486-0098 FU European Molecular Biology Organization [ASTF 82-2014]; US Department of Health and Human Services; European Union [340440]; Agence nationale de la recherche (ANR) program BLANC, project EXAVIR FX MK was partly supported by the European Molecular Biology Organization (ASTF 82-2014). EVK and KSM are supported by intramural funds of the US Department of Health and Human Services (to the National Library of Medicine). PF is supported by the European Union's Seventh Framework Program (FP/2007-2013) / Project EVOMOBIL - ERC Grant Agreement no. 340440. DP is supported by the Agence nationale de la recherche (ANR) program BLANC, project EXAVIR. NR 77 TC 36 Z9 36 U1 3 U2 43 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 MAY 19 PY 2014 VL 12 AR 36 DI 10.1186/1741-7007-12-36 PG 12 WC Biology SC Life Sciences & Biomedicine - Other Topics GA AI4CY UT WOS:000336814400001 PM 24884953 ER PT J AU Gombold, J Karakasidis, S Niksa, P Podczasy, J Neumann, K Richardson, J Sane, N Johnson-Leva, R Randolph, V Sadoff, J Minor, P Schmidt, A Duncan, P Sheets, RL AF Gombold, James Karakasidis, Stephen Niksa, Paula Podczasy, John Neumann, Kitti Richardson, James Sane, Nandini Johnson-Leva, Renita Randolph, Valerie Sadoff, Jerald Minor, Phillip Schmidt, Alexander Duncan, Paul Sheets, Rebecca L. TI Systematic evaluation of in vitro and in vivo adventitious virus assays for the detection of viral contamination of cell banks and biological products SO VACCINE LA English DT Article; Proceedings Paper CT 4th Vaccine Technology Conference in the Engineering Conferences International (ECI) CT 4th Vaccine Technology Conference in the Engineering Conferences International (ECI) CY MAY 20-24, 2012 CY MAY 20-24, 2012 CL Albufeira, PORTUGAL CL Albufeira, PORTUGAL DE Vaccines; Viral safety; In vitro; In vivo; Adventitious agents; 3Rs AB Viral vaccines and the cell substrates used to manufacture them are subjected to tests for adventitious agents, including viruses, contaminate. Some of the compendial methods (in vivo and in vitro in cell culture) were established in the mid-20th century. These methods have not been subjected to current assay validation, as new methods would need to be. This study was undertaken to provide insight into the breadth (selectivity) and sensitivity (limit of detection) of the routine methods, two such validation parameters. Sixteen viral stocks were prepared and characterized. These stocks were tested in serial dilutions by the routine methods to establish which viruses were detected by which methods and above what limit of detection. Sixteen out of sixteen viruses were detected in vitro, though one (bovine viral diarrhea virus) required special conditions to detect and another (rubella virus) was detected with low sensitivity. Many were detected at levels below 1 TCID50 or PFU (titers were established on the production cell line in most cases). In contrast, in vivo, only 6/11 viruses were detected, and 4 of these were detected only at amounts one or more logs above 1 TCID50 or PFU. Only influenza virus and vesicular stomatitis virus were detected at lower amounts in vivo than in vitro. Given the call to reduce, refine, or replace (3Rs) the use of animals in product safety testing and the emergence of new technologies for the detection of viruses, a re-examination of the current adventitious virus testing strategies seems warranted. Suggested pathways forward are offered. Published by Elsevier Ltd. C1 [Gombold, James; Karakasidis, Stephen; Podczasy, John; Neumann, Kitti] Charles River Labs, Malvern, PA 19355 USA. [Niksa, Paula] Charles River Labs, Wilmington, MA 01887 USA. [Richardson, James; Sane, Nandini; Johnson-Leva, Renita] Adv BioSci Labs, Rockville, MD 20850 USA. [Randolph, Valerie] Wyeth, Pearl River, NY 10965 USA. [Sadoff, Jerald] Crucell, NL-2301 CA Leiden, Netherlands. [Minor, Phillip] Natl Inst Biol Stand & Controls, Potters Bar EN6 3QG, Herts, England. [Schmidt, Alexander] GSK Vaccines, NIH, NIAID, B-1330 Rixensart, Belgium. [Duncan, Paul] Merck & Co Inc, West Point, PA 19486 USA. [Sheets, Rebecca L.] NIAID, NIH, Div Aids, Bethesda, MD 20892 USA. RP Sheets, RL (reprint author), NIAID, NIH, Div Aids, 67008 Rockledge Dr,Rm 5145, Bethesda, MD 20892 USA. EM rsheets@grimalkinpartners.com FU National Institute of Allergy and Infectious Diseases, National Institutes of Health, Department of Health and Human Services [HHSN266200400045C] FX This project has been funded in whole or in part with federal funds from the National Institute of Allergy and Infectious Diseases, National Institutes of Health, Department of Health and Human Services, under Contract No. HHSN266200400045C. NR 11 TC 5 Z9 5 U1 1 U2 6 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0264-410X EI 1873-2518 J9 VACCINE JI Vaccine PD MAY 19 PY 2014 VL 32 IS 24 SI SI BP 2916 EP 2926 DI 10.1016/j.vaccine.2014.02.021 PG 11 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA AI2RD UT WOS:000336704900025 PM 24681273 ER PT J AU Shinomiya, K Karuppudurai, T Lin, TY Lu, ZY Lee, CH Meinertzhagen, IA AF Shinomiya, Kazunori Karuppudurai, Thangavel Lin, Tzu-Yang Lu, Zhiyuan Lee, Chi-Hon Meinertzhagen, Ian A. TI Candidate Neural Substrates for Off-Edge Motion Detection in Drosophila SO CURRENT BIOLOGY LA English DT Article ID MUSCARINIC ACETYLCHOLINE-RECEPTORS; ACTIVATED POTASSIUM CHANNEL; VISUAL-SYSTEM; SPECTRAL PREFERENCE; SENSITIVE PATHWAYS; WILD-TYPE; VISION; FLY; MELANOGASTER; CIRCUIT AB Background: In the fly's visual motion pathways, two cell types-T4 and T5-are the first known relay neurons to signal small-field direction-selective motion responses [1]. These cells then feed into large tangential cells that signal wide-field motion. Recent studies have identified two types of columnar neurons in the second neuropil, or medulla, that relay input to 14 from L1, the ON-channel neuron in the first neuropil, or lamina, thus providing a candidate substrate for the elementary motion detector (EMD) [2]. Interneurons relaying the OFF channel from L1's partner, L2, to T5 are so far not known, however. Results: Here we report that multiple types of transmedulla (Tm) neurons provide unexpectedly complex inputs to T5 at their terminals in the third neuropil, or lobula. From the L2 pathway, single-column input comes from Tm1 and Tm2 and multiple-column input from Tm4 cells. Additional input to T5 comes from Tm9, the medulla target of a third lamina interneuron, L3, providing a candidate substrate for L3's combinatorial action with L2 [3]. Most numerous, Tm2 and Tm9's input synapses are spatially segregated on T5's dendritic arbor, providing candidate anatomical substrates for the two arms of a 15 EMD circuit; Tm1 and Tm2 provide a second. Transcript profiling indicates that T5 expresses both nicotinic and muscarinic cholinoceptors, qualifying T5 to receive cholinergic inputs from Tm9 and Tm2, which both express choline acetyltransferase (ChAT). Conclusions: We hypothesize that T5 computes small-field motion signals by integrating multiple cholinergic Tm inputs using nicotinic and muscarinic cholinoceptors. C1 [Shinomiya, Kazunori; Lu, Zhiyuan; Meinertzhagen, Ian A.] Dalhousie Univ, Life Sci Ctr, Dept Psychol & Neurosci, Halifax, NS B3H 4R2, Canada. [Meinertzhagen, Ian A.] Dalhousie Univ, Life Sci Ctr, Dept Biol, Halifax, NS B3H 4R2, Canada. [Karuppudurai, Thangavel; Lin, Tzu-Yang; Lee, Chi-Hon] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Sect Neuronal Connect, Lab Gene Regulat & Dev, NIH, Bethesda, MD 20892 USA. RP Meinertzhagen, IA (reprint author), Dalhousie Univ, Life Sci Ctr, Dept Psychol & Neurosci, Halifax, NS B3H 4R2, Canada. EM iam@dal.ca OI Meinertzhagen, Ian/0000-0002-6578-4526 FU NIH [EY-03592]; Eunice Kennedy Shriven National Institute of Child Health and Human Development, NIH [Z01-HD008776]; Government of Canada Post-Doctoral Research Fellowship from Foreign Affairs and International Trade Canada (DFAIT) FX This work was supported by NIH grant EY-03592 (to I.A.M.) and the Intramural Research Program of the Eunice Kennedy Shriven National Institute of Child Health and Human Development, NIH (grant Z01-HD008776 to C.-H. L.). During part of his work, K.S. was in receipt of a Government of Canada Post-Doctoral Research Fellowship from Foreign Affairs and International Trade Canada (DFAIT). We thank Jane Anne Home (Dalhousie) for assistance in making the EM reconstructions, Chun-Yuan Ting (NIH) for assistance in analyzing synaptic distribution and immunohistochemistry, Mark Stopfer (NIH) for helpful discussions, and Axel Borst (Martinsried) for reagents and communicated intelligence. NR 59 TC 29 Z9 29 U1 2 U2 12 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 0960-9822 EI 1879-0445 J9 CURR BIOL JI Curr. Biol. PD MAY 19 PY 2014 VL 24 IS 10 BP 1062 EP 1070 DI 10.1016/j.cub.2014.03.051 PG 9 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA AH7UE UT WOS:000336340000028 PM 24768048 ER PT J AU Beach, JR Shao, L Remmert, K Li, D Betzig, E Hammer, JA AF Beach, Jordan R. Shao, Lin Remmert, Kirsten Li, Dong Betzig, Eric Hammer, John A., III TI Nonmuscle Myosin II Isoforms Coassemble in Living Cells SO CURRENT BIOLOGY LA English DT Article ID LIVE CELLS; STRUCTURED ILLUMINATION; FILAMENTS; DEFECTS; TAIL; PHOSPHORYLATION; MICROSCOPY; MIGRATION; DYNAMICS; ADHESION AB Nonmuscle myosin II (NM II) powers myriad developmental and cellular processes, including embryogenesis, cell migration, and cytokinesis [1]. To exert its functions, monomers of NM II assemble into bipolar filaments that produce a contractile force on the actin cytoskeleton. Mammalian cells express up to three isoforms of NM II (NM IIA, IIB, and IIC), each of which possesses distinct biophysical properties and supports unique as well as redundant cellular functions [2-8]. Despite previous efforts [9-13], it remains unclear whether NM II isoforms assemble in living cells to produce mixed (heterotypic) bipolar filaments or whether filaments consist entirely of a single isoform (homotypic). We addressed this question using fluorescently tagged versions of NM IIA, IIB, and IIC, isoform-specific immunostaining of the endogenous proteins, and two-color total internal reflection fluorescence structured-illumination microscopy, or TIRF-SIM, to visualize individual myosin II bipolar filaments inside cells. We show that NM II isoforms coassemble into heterotypic filaments in a variety of settings, including various types of stress fibers, individual filaments throughout the cell, and the contractile ring. We also show that the differential distribution of NM IIA and NM IIB typically seen in confocal micrographs of well-polarized cells is reflected in the composition of individual bipolar filaments. Interestingly, this differential distribution is less pronounced in freshly spread cells, arguing for the existence of a sorting mechanism acting over time. Together, our work argues that individual NM II isoforms are potentially performing both isoform-specific and isoform-redundant functions while coassembled with other NM II isoforms. C1 [Beach, Jordan R.; Remmert, Kirsten; Hammer, John A., III] NHLBI, Cell Biol & Physiol Ctr, NIH, Bethesda, MD 20892 USA. [Shao, Lin; Li, Dong; Betzig, Eric] Howard Hughes Med Inst, Ashburn, VA 20147 USA. RP Beach, JR (reprint author), NHLBI, Cell Biol & Physiol Ctr, NIH, Bethesda, MD 20892 USA. EM jordan.beach@nih.gov; hammerj@nhibi.nih.gov FU Intramural NIH HHS [Z01 HL000514-24] NR 30 TC 38 Z9 38 U1 2 U2 44 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 0960-9822 EI 1879-0445 J9 CURR BIOL JI Curr. Biol. PD MAY 19 PY 2014 VL 24 IS 10 BP 1160 EP 1166 DI 10.1016/j.cub.2014.03.071 PG 7 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA AH7UE UT WOS:000336340000042 PM 24814144 ER PT J AU Zipprer, EM Neggers, M Kushwaha, A Rayavara, K Desai, SA AF Zipprer, Elizabeth M. Neggers, McKinzie Kushwaha, Ambuj Rayavara, Kempaiah Desai, Sanjay A. TI A kinetic fluorescence assay reveals unusual features of Ca++ uptake in Plasmodium falciparum-infected erythrocytes SO MALARIA JOURNAL LA English DT Article DE Calcium channels; Malaria parasites; Human erythrocytes; Fluo-8; Fluorescence kinetics; Antimalarial drug discovery ID RED-BLOOD-CELLS; SURFACE ANION CHANNEL; THROUGHPUT SCREENING ASSAYS; MALARIA-PARASITE; CALCIUM-TRANSPORT; NUTRIENT-UPTAKE; RESISTANCE; CA2+; SELECTIVITY; VALIDATION AB Background: To facilitate development within erythrocytes, malaria parasites increase their host cell uptake of diverse solutes including Ca++. The mechanism and molecular basis of increased Ca++ permeability remains less well studied than that of other solutes. Methods: Based on an appropriate Ca++ affinity and its greater brightness than related fluorophores, Fluo-8 was selected and used to develop a robust fluorescence-based assay for Ca++ uptake by human erythrocytes infected with Plasmodium falciparum. Results: Both uninfected and infected cells exhibited a large Ca++-dependent fluorescence signal after loading with the Fluo-8 dye. Probenecid, an inhibitor of erythrocyte organic anion transporters, abolished the fluorescence signal in uninfected cells; in infected cells, this agent increased fluorescence via mechanisms that depend on parasite genotype. Kinetic fluorescence measurements in 384-well microplates revealed that the infected cell Ca++ uptake is not mediated by the plasmodial surface anion channel (PSAC), a parasite nutrient channel at the host membrane; it also appears to be distinct from mammalian Ca++ channels. Imaging studies confirmed a low intracellular Ca++ in uninfected cells and higher levels in both the host and parasite compartments of infected cells. Parasite growth inhibition studies revealed a conserved requirement for extracellular Ca++. Conclusions: Nondestructive loading of Fluo-8 into human erythrocytes permits measurement of Ca++ uptake kinetics. The greater Ca++ permeability of cells infected with malaria parasites is apparent when probenecid is used to inhibit Fluo-8 efflux at the host membrane. This permeability is mediated by a distinct pathway and may be essential for intracellular parasite development. The miniaturized assay presented here should help clarify the precise transport mechanism and may identify inhibitors suitable for antimalarial drug development. C1 [Zipprer, Elizabeth M.; Neggers, McKinzie; Kushwaha, Ambuj; Rayavara, Kempaiah; Desai, Sanjay A.] NIAID, Lab Malaria & Vector Res, NIH, Bethesda, MD 20892 USA. RP Desai, SA (reprint author), NIAID, Lab Malaria & Vector Res, NIH, Bethesda, MD 20892 USA. EM sdesai@niaid.nih.gov FU Intramural NIAID Research Opportunities program (INRO); Intramural Research Program of the National Institutes of Health, National Institute of Allergy and Infectious Diseases, USA FX EMZ and MN received support from the Intramural NIAID Research Opportunities program (INRO). This research was supported by the Intramural Research Program of the National Institutes of Health, National Institute of Allergy and Infectious Diseases, USA. NR 48 TC 2 Z9 2 U1 1 U2 7 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1475-2875 J9 MALARIA J JI Malar. J. PD MAY 18 PY 2014 VL 13 AR 184 DI 10.1186/1475-2875-13-184 PG 11 WC Infectious Diseases; Parasitology; Tropical Medicine SC Infectious Diseases; Parasitology; Tropical Medicine GA AI1SJ UT WOS:000336632100001 PM 24885754 ER PT J AU Murphy, SC Hermsen, CC Douglas, AD Edwards, NJ Petersen, I Fahle, GA Adams, M Berry, AA Billman, ZP Gilbert, SC Laurens, MB Leroy, O Lyke, KE Plowe, CV Seilie, AM Strauss, KA Teelen, K Hill, AVS Sauerwein, RW AF Murphy, Sean C. Hermsen, Cornelus C. Douglas, Alexander D. Edwards, Nick J. Petersen, Ines Fahle, Gary A. Adams, Matthew Berry, Andrea A. Billman, Zachary P. Gilbert, Sarah C. Laurens, Matthew B. Leroy, Odile Lyke, Kristen E. Plowe, Christopher V. Seilie, Annette M. Strauss, Kathleen A. Teelen, Karina Hill, Adrian V. S. Sauerwein, Robert W. TI External Quality Assurance of Malaria Nucleic Acid Testing for Clinical Trials and Eradication Surveillance SO PLOS ONE LA English DT Article ID REAL-TIME PCR; POLYMERASE-CHAIN-REACTION; SEQUENCE-BASED AMPLIFICATION; PLASMODIUM-FALCIPARUM DNA; RAPID DIAGNOSTIC-TESTS; NONREPLICATING SPOROZOITE VACCINE; MEDIATED ISOTHERMAL AMPLIFICATION; T-CELL IMMUNITY; INFECTED MOSQUITOS; ENDEMIC AREA AB Nucleic acid testing (NAT) for malaria parasites is an increasingly recommended diagnostic endpoint in clinical trials of vaccine and drug candidates and is also important in surveillance of malaria control and elimination efforts. A variety of reported NAT assays have been described, yet no formal external quality assurance (EQA) program provides validation for the assays in use. Here, we report results of an EQA exercise for malaria NAT assays. Among five centers conducting controlled human malaria infection trials, all centers achieved 100% specificity and demonstrated limits of detection consistent with each laboratory's pre-stated expectations. Quantitative bias of reported results compared to expected results was generally <0.5 log(10) parasites/mL except for one laboratory where the EQA effort identified likely reasons for a general quantitative shift. The within-laboratory variation for all assays was low at <10% coefficient of variation across a range of parasite densities. Based on this study, we propose to create a Molecular Malaria Quality Assessment program that fulfills the need for EQA of malaria NAT assays worldwide. C1 [Murphy, Sean C.; Billman, Zachary P.; Seilie, Annette M.] Univ Washington, Dept Lab Med, Seattle, WA 98195 USA. [Murphy, Sean C.; Billman, Zachary P.; Seilie, Annette M.] Univ Washington, Ctr Emerging & Re Emerging Infect Dis, Seattle, WA 98195 USA. [Hermsen, Cornelus C.; Teelen, Karina; Sauerwein, Robert W.] Radboud Univ Nijmegen Med Ctr, Dept Med Microbiol, Nijmegen, Netherlands. [Douglas, Alexander D.; Edwards, Nick J.; Gilbert, Sarah C.; Hill, Adrian V. S.] Univ Oxford, Jenner Inst, Oxford, England. [Petersen, Ines; Leroy, Odile] European Vaccine Initiat, Heidelberg, Germany. [Fahle, Gary A.] NIH, Dept Lab Med, Ctr Clin, Bethesda, MD 20892 USA. [Adams, Matthew; Berry, Andrea A.; Laurens, Matthew B.; Lyke, Kristen E.; Plowe, Christopher V.; Strauss, Kathleen A.] Univ Maryland, Sch Med, Ctr Vaccine Dev, Baltimore, MD 21201 USA. [Adams, Matthew; Berry, Andrea A.; Laurens, Matthew B.; Lyke, Kristen E.; Plowe, Christopher V.; Strauss, Kathleen A.] Univ Maryland, Sch Med, Howard Hughes Med Inst, Baltimore, MD 21201 USA. RP Murphy, SC (reprint author), Univ Washington, Dept Lab Med, Seattle, WA 98195 USA. EM murphysc@uw.edu RI Douglas, Alexander/E-7040-2012; Sauerwein, Robert/C-8519-2013; Hermsen, C.C./L-4368-2015; Laurens, Matthew/E-7293-2013 OI Edwards, Nick/0000-0002-7030-7839; Douglas, Alexander/0000-0002-5410-7562; Laurens, Matthew/0000-0003-3874-581X FU UW Center for AIDS Research [AI27757]; non-UW labs FX This work was supported using intra-Departmental funds (to SCM) and resources from the UW Center for AIDS Research (AI27757). Testing at non-UW labs was paid for by those institutions using in-house support. No commercial funding was used for this study. Study design, data collection, analysis, decision to publish and preparation of the manuscript were wholly the responsibility of the listed authors and no one else. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 76 TC 6 Z9 6 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 MAY 16 PY 2014 VL 9 IS 5 AR e97398 DI 10.1371/journal.pone.0097398 PG 9 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA AM1NZ UT WOS:000339614800042 PM 24838112 ER PT J AU Kumar, S Yedjou, CG Tchounwou, PB AF Kumar, Sanjay Yedjou, Clement G. Tchounwou, Paul B. TI Arsenic trioxide induces oxidative stress, DNA damage, and mitochondrial pathway of apoptosis in human leukemia (HL-60) cells SO JOURNAL OF EXPERIMENTAL & CLINICAL CANCER RESEARCH LA English DT Article DE Arsenic trioxide; Oxidative stress; DNA damage; Apoptosis; HL-60 cells ID ACUTE PROMYELOCYTIC LEUKEMIA; DOWN-REGULATION; CANCER CELLS; IN-VITRO; COMPLETE REMISSION; CARCINOMA CELLS; RETINOIC ACID; CYCLE ARREST; INDUCTION; LINES AB Background: Acute promyelocytic leukemia (APL) is a subtype of acute myeloid leukemia (AML), which accounts for approximately 10% of all acute myloid leukemia cases. It is a blood cancer that is formed by chromosomal mutation. Each year in the United States, APL affects about 1,500 patients of all age groups and causes approximately 1.2% of cancer deaths. Arsenic trioxide (ATO) has been used successfully for treatment of APL patients, and both induction and consolidated therapy have resulted in complete remission. Recently published studies from our laboratory have demonstrated that ATO pharmacology as an anti-leukemic drug is associated with cytotoxic and genotoxic effects in leukemia cells. Methods: In the present study, we further investigated the detailed molecular mechanism of ATO-mediated intrinsic pathway of apoptosis; using HL-60 cells as a test model. Oxidative stress was assessed by spectrophotometric measurements of MDA and GSH levels while genotoxicity was determined by single cell gel electrophoresis (Comet assay). Apoptosis pathway was analyzed by Western blot analysis of Bax, Bcl2 and caspase 3 expression, as well as immunocytochemistry and confocal imaging of Bax and Cyt c translocation and mitochondrial membrane potential depolarization. Results: ATO significantly (p < 0.05) induces oxidative stress, DNA damage, and caspase 3 activityin HL-60 cells in a dose-dependent manner. It also activated the intrinsic pathway of apoptosis by significantly modulating (p < 0.05) the expression and translocation of apoptotic molecules and decreasing the mitochondrial membrane potential in leukemia cells. Conclusion: Taken together, our research demonstrated that ATO induces mitochondrial pathway of apoptosis in HL-60 cells. This apoptotic signaling is modulated via oxidative stress, DNA damage, and change in mitochondrial membrane potential, translocation and upregulation of apoptotic proteins leading programmed cell death. C1 [Kumar, Sanjay; Yedjou, Clement G.; Tchounwou, Paul B.] Jackson State Univ, Coll Sci Engn & Technol, Cell & Toxicogen Res Lab, NIH NIMHD RCMI Ctr Environm Hlth, Jackson, MS 39217 USA. RP Tchounwou, PB (reprint author), Jackson State Univ, Coll Sci Engn & Technol, Cell & Toxicogen Res Lab, NIH NIMHD RCMI Ctr Environm Hlth, 1400 Lunch St,Box18750, Jackson, MS 39217 USA. EM paul.b.tchounwou@jsums.edu FU National Institutes of Health through the RCMI Center for Environmental Health at Jackson State University [G12MD007581] FX The research described in this publication was made possible by a grant from the National Institutes of Health (Grant No. G12MD007581) through the RCMI Center for Environmental Health at Jackson State University. NR 51 TC 18 Z9 18 U1 1 U2 18 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1756-9966 J9 J EXP CLIN CANC RES JI J. Exp. Clin. Cancer Res. PD MAY 16 PY 2014 VL 33 AR 42 DI 10.1186/1756-9966-33-42 PG 12 WC Oncology SC Oncology GA AI6OQ UT WOS:000336995300001 PM 24887205 ER PT J AU Zhang, L Beaucher, M Cheng, Y Rong, YKS AF Zhang, Liang Beaucher, Michelle Cheng, Yan Rong, Yikang S. TI Coordination of transposon expression with DNA replication in the targeting of telomeric retrotransposons in Drosophila SO EMBO JOURNAL LA English DT Article DE CST complex; Drosophila telomere; telomere replication; telomeric transposon ID NON-LTR RETROTRANSPOSONS; CHROMOSOME ENDS; HET-A; MELANOGASTER TELOMERES; PROTEIN; ELONGATION; RETROVIRUS; ELEMENTS; MAINTENANCE; CENTROMERES AB In Drosophila, a group of retrotransposons is mobilized exclusively to telomeres in a sequence-independent manner. How they target chromosome ends is not understood. Here, we focused on the telomeric element HeT-A and characterized the cell cycle expression and cytological distribution of its protein and RNA products. We determined the timing of telomere replication by creating a single lacO-marked telomere and provide evidence suggesting that transposon expression and recruitment to telomeres is linked to telomere replication. The HeT-A-encoded ORF1p protein is expressed predominantly in S phase, particularly in early S phase. Orf1p binds HeT-A transcripts and forms spherical structures at telomeres undergoing DNA replication. HeT-A sphere formation requires Verrocchio, a putative homolog of the conserved Stn1 telomeric protein. Our results suggest that coupling of telomere elongation and telomere replication is a universal feature, and raise the possibility that transposon recruitment to Drosophila telomeres is mechanistically related to telomerase recruitment in other organisms. Our study also supports a co-adaptive relationship between the Drosophila host and HeT-A mobile elements. C1 [Zhang, Liang; Beaucher, Michelle; Cheng, Yan; Rong, Yikang S.] NCI, Biochem & Mol Biol Lab, NIH, Bethesda, MD 20892 USA. RP Rong, YKS (reprint author), NCI, Biochem & Mol Biol Lab, NIH, Bethesda, MD 20892 USA. EM rongy@mail.nih.gov FU intramural research program of the National Cancer Institute FX We thank Ms. Sara Brinda and Ms. Flavia Amariei for their technical assistance. We thank Drs. Bob Levis, Mary-Lou Pardue, Bruce Paterson, and members of our laboratory for comments on the manuscript. We thank Dr. Jemima Barrowman at NCI for editing the manuscript. Research in the laboratory is supported by the intramural research program of the National Cancer Institute. NR 49 TC 8 Z9 8 U1 3 U2 6 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0261-4189 EI 1460-2075 J9 EMBO J JI Embo J. PD MAY 16 PY 2014 VL 33 IS 10 BP 1148 EP 1158 DI 10.1002/embj.201386940 PG 11 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA AH9WN UT WOS:000336495900007 PM 24733842 ER PT J AU Biswas, D Hrabie, JA Saavedra, JE Cao, Z Keefer, LK Ivanic, J Holland, RJ AF Biswas, Debanjan Hrabie, Joseph A. Saavedra, Joseph E. Cao, Zhao Keefer, Larry K. Ivanic, Joseph Holland, Ryan J. TI Aminolysis of an N-Diazeniumdiolated Amidine as an Approach to Diazeniumdiolated Ammonia SO JOURNAL OF ORGANIC CHEMISTRY LA English DT Article ID BASIS-SETS; OXIDE; CHEMISTRY; RELEASE; AMINES AB Recent theoretical studies have suggested that the parent diazeniumdiolate ion, H2N-N(O)=NO- ("diazeniumdiolated ammonia"), might be stable enough to be isolated and that it could potentially serve as a uniquely advantageous prodrug form of bioactive nitroxyl (HNO). Here, we report on an attempt to isolate its O-2-benzylated derivative by aminolysis of the C=N bond in PhC(NH2)=N-N(O)=NOBn. The reaction proved remarkably sluggish in comparison to aminolysis of unsubstituted benzamidine, and the desired product could not be isolated, apparently because of base sensitivity of the NH2 group. Consistent with this interpretation, O-benzylhydroxylamine and N2O were recovered from the reaction mixture in high yields, along with N,N'-dibutylbenzamidine. Theoretical calculations rationalize the observed slow aminolysis by demonstrating that the diazeniumdiolate group greatly suppresses the electrophilicity of the adjacent C=N carbon center, rendering attack at that position endothermic. The data provide significant insights into the challenges inherent to the pursuit of diazeniumdiolated ammonia. C1 [Biswas, Debanjan; Hrabie, Joseph A.; Keefer, Larry K.; Holland, Ryan J.] Leidos Biomed Res Inc, Drug Design Sect, Biol Chem Lab, Frederick Natl Lab Canc Res, Frederick, MD 21702 USA. [Saavedra, Joseph E.; Cao, Zhao] Leidos Biomed Res Inc, Basic Sci Program, Frederick Natl Lab Canc Res, Frederick, MD 21702 USA. [Ivanic, Joseph] Leidos Biomed Res Inc, Adv Biomed Comp Ctr, Informat Syst Program, Frederick Natl Lab Canc Res, Frederick, MD 21702 USA. RP Holland, RJ (reprint author), Leidos Biomed Res Inc, Drug Design Sect, Biol Chem Lab, Frederick Natl Lab Canc Res, Frederick, MD 21702 USA. EM hollandrj@mail.nih.gov RI Keefer, Larry/N-3247-2014 OI Keefer, Larry/0000-0001-7489-9555 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 with federal funds from the National Cancer Institute, National Institutes of Health, under Contract No. HHSN261200800001E, and by the Intramural Research Program of the NIH, National Cancer Institute, Center for Cancer Research. We thank Dr. Sergey Tarasov and Ms. Marzena A. Dyba of the Biophysics Resource in the Structural Biophysics Laboratory, NCI-Frederick, for assistance with the high-resolution mass spectrometry studies. NR 18 TC 0 Z9 0 U1 0 U2 9 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0022-3263 J9 J ORG CHEM JI J. Org. Chem. PD MAY 16 PY 2014 VL 79 IS 10 BP 4512 EP 4516 DI 10.1021/jo500551n PG 5 WC Chemistry, Organic SC Chemistry GA AH5VS UT WOS:000336199800030 PM 24766285 ER PT J AU Davis, MI Gross, S Shen, M Straley, KS Pragani, R Lea, WA Popovici-Muller, J DeLaBarre, B Artin, E Thorne, N Auld, DS Li, ZY Dang, L Boxer, MB Simeonov, A AF Davis, Mindy I. Gross, Stefan Shen, Min Straley, Kimberly S. Pragani, Rajan Lea, Wendy A. Popovici-Muller, Janeta DeLaBarre, Byron Artin, Erin Thorne, Natasha Auld, Douglas S. Li, Zhuyin Dang, Lenny Boxer, Matthew B. Simeonov, Anton TI Biochemical, Cellular, and Biophysical Characterization of a Potent Inhibitor of Mutant Isocitrate Dehydrogenase IDH1 SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article DE Dehydrogenase; Drug Discovery; Enzyme Inhibitors; Glioblastoma; Small Molecules; AML; IDH1; Isocitrate Dehydrogenase; Enzyme ID ONCOMETABOLITE 2-HYDROXYGLUTARATE; CANCER GENOME; GLIOMA-CELLS; MUTATIONS; LEUKEMIA AB Background: IDH1 R132H, implicated in glioblastoma and AML, produces the oncometabolite 2-HG. Results: A detailed binding mechanism of a small molecule inhibitor (ML309) is proposed. Conclusion: ML309 competes with -KG but is uncompetitive with NADPH and rapidly and reversibly affects cellular 2-HG levels. Significance: Understanding IDH1 R132H inhibition sets the stage for targeting IDH1 R132H for the treatment of cancer. Two mutant forms (R132H and R132C) of isocitrate dehydrogenase 1 (IDH1) have been associated with a number of cancers including glioblastoma and acute myeloid leukemia. These mutations confer a neomorphic activity of 2-hydroxyglutarate (2-HG) production, and 2-HG has previously been implicated as an oncometabolite. Inhibitors of mutant IDH1 can potentially be used to treat these diseases. In this study, we investigated the mechanism of action of a newly discovered inhibitor, ML309, using biochemical, cellular, and biophysical approaches. Substrate binding and product inhibition studies helped to further elucidate the IDH1 R132H catalytic cycle. This rapidly equilibrating inhibitor is active in both biochemical and cellular assays. The (+) isomer is active (IC50 = 68 nm), whereas the (-) isomer is over 400-fold less active (IC50 = 29 m) for IDH1 R132H inhibition. IDH1 R132C was similarly inhibited by (+)-ML309. WT IDH1 was largely unaffected by (+)-ML309 (IC50 >36 m). Kinetic analyses combined with microscale thermophoresis and surface plasmon resonance indicate that this reversible inhibitor binds to IDH1 R132H competitively with respect to -ketoglutarate and uncompetitively with respect to NADPH. A reaction scheme for IDH1 R132H inhibition by ML309 is proposed in which ML309 binds to IDH1 R132H after formation of the IDH1 R132H NADPH complex. ML309 was also able to inhibit 2-HG production in a glioblastoma cell line (IC50 = 250 nm) and had minimal cytotoxicity. In the presence of racemic ML309, 2-HG levels drop rapidly. This drop was sustained until 48 h, at which point the compound was washed out and 2-HG levels recovered. C1 [Davis, Mindy I.; Shen, Min; Pragani, Rajan; Lea, Wendy A.; Thorne, Natasha; Auld, Douglas S.; Li, Zhuyin; Boxer, Matthew B.; Simeonov, Anton] NIH, NIH Chem Genom Ctr, Natl Ctr Adv Translat Sci, Rockville, MD 20892 USA. [Gross, Stefan; Straley, Kimberly S.; Popovici-Muller, Janeta; DeLaBarre, Byron; Artin, Erin; Dang, Lenny] Agios Pharmaceut Inc, Cambridge, MA 02139 USA. [Auld, Douglas S.] Ctr Prote Chem, Novartis Inst Biomed Res, Cambridge, MA 02139 USA. RP Simeonov, A (reprint author), NIH, NIH Chem Genom Ctr, Natl Ctr Adv Translat Sci, 9800 Med Ctr Dr, Rockville, MD 20892 USA. EM asimeono@mail.nih.gov FU Molecular Libraries Initiative of the National Institutes of Health Roadmap for Medical Research, National Institutes of Health [U54 MH084681] FX This research was supported by the Molecular Libraries Initiative of the National Institutes of Health Roadmap for Medical Research, National Institutes of Health (U54 MH084681). NR 24 TC 31 Z9 31 U1 2 U2 27 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 MAY 16 PY 2014 VL 289 IS 20 BP 13717 EP 13725 DI 10.1074/jbc.M113.511030 PG 9 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA AH2XF UT WOS:000335984600006 PM 24668804 ER PT J AU Sassa, A Caglayan, M Dyrkheeva, NS Beard, WA Wilson, SH AF Sassa, Akira Caglayan, Melike Dyrkheeva, Nadezhda S. Beard, William A. Wilson, Samuel H. TI Base Excision Repair of Tandem Modifications in a Methylated CpG Dinucleotide SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article DE Base Excision Repair; DNA Damage; DNA Methylation; DNA Polymerase; Oxidative Stress; 8-Oxoguanine; DNA Demethylation; DNA Glycosylase ID THYMINE-DNA GLYCOSYLASE; POLYMERASE-BETA; HUMAN-CELLS; 8-OXOGUANINE-DNA GLYCOSYLASE; APURINIC ENDONUCLEASE-1; SUBSTRATE-SPECIFICITY; OXIDATIVE DAMAGE; AP-ENDONUCLEASE; INITIAL STEPS; MAMMALIAN DNA AB Background: Base excision repair is an important pathway for cytosine demethylation at the CpG dinucleotide for epigenetic control. Results: A deaminated 5-methylcytosine (thymine) and an adjacent oxidized guanine (7,8-dihydro-8-oxoguanine) retard base excision repair of each lesion. Conclusion: Altered in-tandem CpG dinucleotide is a poor substrate for base excision repair. Significance: Oxidized guanine in a CpG dinucleotide interferes with active DNA demethylation. Cytosine methylation and demethylation in tracks of CpG dinucleotides is an epigenetic mechanism for control of gene expression. The initial step in the demethylation process can be deamination of 5-methylcytosine producing the TpG alteration and T:G mispair, and this step is followed by thymine DNA glycosylase (TDG) initiated base excision repair (BER). A further consideration is that guanine in the CpG dinucleotide may become oxidized to 7,8-dihydro-8-oxoguanine (8-oxoG), and this could affect the demethylation process involving TDG-initiated BER. However, little is known about the enzymology of BER of altered in-tandem CpG dinucleotides; e.g. Tp8-oxoG. Here, we investigated interactions between this altered dinucleotide and purified BER enzymes, the DNA glycosylases TDG and 8-oxoG DNA glycosylase 1 (OGG1), apurinic/apyrimidinic (AP) endonuclease 1, DNA polymerase , and DNA ligases. The overall TDG-initiated BER of the Tp8-oxoG dinucleotide is significantly reduced. Specifically, TDG and DNA ligase activities are reduced by a 3-flanking 8-oxoG. In contrast, the OGG1-initiated BER pathway is blocked due to the 5-flanking T:G mispair; this reduces OGG1, AP endonuclease 1, and DNA polymerase activities. Furthermore, in TDG-initiated BER, TDG remains bound to its product AP site blocking OGG1 access to the adjacent 8-oxoG. These results reveal BER enzyme specificities enabling suppression of OGG1-initiated BER and coordination of TDG-initiated BER at this tandem alteration in the CpG dinucleotide. C1 [Sassa, Akira; Caglayan, Melike; Dyrkheeva, Nadezhda S.; Beard, William A.; Wilson, Samuel H.] NIEHS, Struct Biol Lab, NIH, Res Triangle Pk, NC 27709 USA. [Dyrkheeva, Nadezhda S.] Russian Acad Sci, Siberian Branch, Inst Chem Biol & Fundamental Med, Novosibirsk 630090, Russia. RP Wilson, SH (reprint author), NIEHS, Struct Biol Lab, NIH, POB 12233, Res Triangle Pk, NC 27709 USA. EM wilson5@niehs.nih.gov FU National Institutes of Health [Z01-ES050158, Z01-ES050159]; Eli Lilly and Co.; United States Department of State, as part of the United States-Russia Collaboration in the Biomedical Sciences NIH Visiting Fellows Program FX This work was supported, in whole or in part, by National Institutes of Health Grants Z01-ES050158 and Z01-ES050159 (NIEHS).; Supported in part by Eli Lilly and Co. and the United States Department of State, as part of the United States-Russia Collaboration in the Biomedical Sciences NIH Visiting Fellows Program. NR 80 TC 8 Z9 11 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 MAY 16 PY 2014 VL 289 IS 20 BP 13996 EP 14008 DI 10.1074/jbc.M114.557769 PG 13 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA AH2XF UT WOS:000335984600030 PM 24695738 ER PT J AU Chen, SR Chen, H Yuan, WX Wess, J Pan, HL AF Chen, Shao-Rui Chen, Hong Yuan, Wei-Xiu Wess, Juergen Pan, Hui-Lin TI Differential Regulation of Primary Afferent Input to Spinal Cord by Muscarinic Receptor Subtypes Delineated Using Knockout Mice SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article DE Acetylcholinesterase; Cholinergic Receptor; Gene Knockout; Glutamate; Neurons; Pain; Synaptic Plasticity; Acetylcholine; Muscarinic; Spinal Cord ID DORSAL-HORN NEURONS; METABOTROPIC GLUTAMATE RECEPTORS; SUBSTANTIA GELATINOSA NEURONS; ACETYLCHOLINE-RECEPTOR; CHOLINERGIC RECEPTORS; AUTORADIOGRAPHIC LOCALIZATION; CHOLINESTERASE INHIBITION; SYNAPTIC-TRANSMISSION; GABA(B) RECEPTORS; GLYCINERGIC INPUT AB Background: Activation of muscarinic receptors reduces pain at the spinal level. Results: M-2 and M-4 subtypes mediate muscarinic inhibition of sensory nerve input. M-5 subtype stimulation directly increases sensory input or indirectly inhibits it through metabotropic glutamate receptors. Conclusion: M-2, M-4, and M-5 subtypes differentially regulate nociceptive input to the spinal cord. Significance: This study demonstrates how individual muscarinic receptor subtypes control pain transmission. Stimulation of muscarinic acetylcholine receptors (mAChRs) inhibits nociceptive transmission at the spinal level. However, it is unclear how each mAChR subtype regulates excitatory synaptic input from primary afferents. Here we examined excitatory postsynaptic currents (EPSCs) of dorsal horn neurons evoked by dorsal root stimulation in spinal cord slices from wild-type and mAChR subtype knock-out (KO) mice. In wild-type mice, mAChR activation with oxotremorine-M decreased the amplitude of monosynaptic EPSCs in approximate to 67% of neurons but increased it in approximate to 10% of neurons. The inhibitory effect of oxotremorine-M was attenuated by the M-2/M-4 antagonist himbacine in the majority of neurons, and the remaining inhibition was abolished by group II/III metabotropic glutamate receptor (mGluR) antagonists in wild-type mice. In M-2/M-4 double-KO mice, oxotremorine-M inhibited monosynaptic EPSCs in significantly fewer neurons (approximate to 26%) and increased EPSCs in significantly more neurons (33%) compared with wild-type mice. Blocking group II/III mGluRs eliminated the inhibitory effect of oxotremorine-M in M-2/M-4 double-KO mice. In M-2 single-KO and M-4 single-KO mice, himbacine still significantly reduced the inhibitory effect of oxotremorine-M. However, the inhibitory and potentiating effects of oxotremorine-M on EPSCs in M-3 single-KO and M-1/M-3 double-KO mice were similar to those in wild-type mice. In M-5 single-KO mice, oxotremorine-M failed to potentiate evoked EPSCs, and its inhibitory effect was abolished by himbacine. These findings indicate that activation of presynaptic M-2 and M-4 subtypes reduces glutamate release from primary afferents. Activation of the M-5 subtype either directly increases primary afferent input or inhibits it through indirectly stimulating group II/III mGluRs. C1 [Chen, Shao-Rui; Chen, Hong; Yuan, Wei-Xiu; Pan, Hui-Lin] Univ Texas MD Anderson Canc Ctr, Dept Anesthesiol & Perioperat Med, Ctr Neurosci & Pain Res, Houston, TX 77030 USA. [Wess, Juergen] NIDDK, Bioorgan Chem Lab, Natl Inst Hlth, Bethesda, MD 20892 USA. RP Pan, HL (reprint author), Univ Texas MD Anderson Canc Ctr, Dept Anesthesiol & Perioperat Med, Unit 110, 1515 Holcombe Blvd, Houston, TX 77030 USA. EM huilinpan@mdanderson.org FU National Institutes of Health [NS073935, NS045602]; N. G. and Helen T. Hawkins Endowment; Intramural Research Program of NIDDK, National Institutes of Health FX This work was supported, in whole or in part, by National Institutes of Health Grants NS073935 and NS045602. This work was also supported by a grant from the N. G. and Helen T. Hawkins Endowment (to H.-L. P.).; Supported by the Intramural Research Program of NIDDK, National Institutes of Health. NR 44 TC 5 Z9 5 U1 2 U2 8 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 MAY 16 PY 2014 VL 289 IS 20 BP 14321 EP 14330 DI 10.1074/jbc.M114.550384 PG 10 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA AH2XF UT WOS:000335984600057 PM 24695732 ER PT J AU Fauci, AS AF Fauci, Anthony S. TI Untitled SO JAVMA-JOURNAL OF THE AMERICAN VETERINARY MEDICAL ASSOCIATION LA English DT News Item C1 NIAID, NIH, Bethesda, MD 20892 USA. RP Fauci, AS (reprint author), NIAID, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER VETERINARY MEDICAL ASSOC PI SCHAUMBURG PA 1931 N MEACHAM RD SUITE 100, SCHAUMBURG, IL 60173-4360 USA SN 0003-1488 EI 1943-569X J9 JAVMA-J AM VET MED A JI JAVMA-J. Am. Vet. Med. Assoc. PD MAY 15 PY 2014 VL 244 IS 10 BP 1103 EP 1104 PG 2 WC Veterinary Sciences SC Veterinary Sciences GA CA6CE UT WOS:000348995200001 ER PT J AU Greer, YE Westlake, CJ Gao, B Bharti, K Shiba, Y Xavier, CP Pazour, GJ Yang, YZ Rubin, JS AF Greer, Yoshimi Endo Westlake, Christopher J. Gao, Bo Bharti, Kapil Shiba, Yoko Xavier, Charles P. Pazour, Gregory J. Yang, Yingzi Rubin, Jeffrey S. TI Casein kinase 1 delta functions at the centrosome and Golgi to promote ciliogenesis SO MOLECULAR BIOLOGY OF THE CELL LA English DT Article ID INTRAFLAGELLAR TRANSPORT; PRIMARY CILIUM; CILIARY MEMBRANE; I FAMILY; PROTEIN; COMPLEX; TRAFFICKING; RAB11; MICROTUBULES; ORGANIZATION AB Inhibition of casein kinase 1 delta (CK1 delta) blocks primary ciliogenesis in human telomerase reverse transcriptase immortalized retinal pigmented epithelial and mouse inner medullary collecting duct cells-3. Mouse embryonic fibroblasts (MEFs) and retinal cells from Csnk1d (CK1 delta)-null mice also exhibit ciliogenesis defects. CK1 delta catalytic activity and centrosomal localization signal (CLS) are required to rescue cilia formation in MEFs(Csnk1d null). Furthermore, expression of a truncated derivative containing the CLS displaces full-length CK1 delta from the centrosome and decreases ciliary length in control MEFs, suggesting that centrosomal CK1 delta has a role in ciliogenesis. CK1 delta inhibition also alters pericentrosomal or ciliary distribution of several proteins involved in ciliary transport, including Ras-like in rat brain11A, Ras-like in rat brain-8A, centrosomal protein of 290 kDa, pericentriolar material protein 1, and polycystin-2, as well as the Golgi distribution of its binding partner, A-kinase anchor protein 450 (AKAP450). As reported for AKAP450, CK1 delta was required for microtubule nucleation at the Golgi and maintenance of Golgi integrity. Overexpression of an AKAP450 fragment containing the CK1 delta-binding site inhibits Golgi-derived microtubule nucleation, Golgi distribution of intraflagellar transport protein 20 homologue, and ciliogenesis. Our results suggest that CK1 delta mediates primary ciliogenesis by multiple mechanisms, one involving its centrosomal function and another dependent on its interaction with AKAP450 at the Golgi, where it is important for maintaining Golgi organization and polarized trafficking of multiple factors that mediate ciliary transport. C1 [Greer, Yoshimi Endo; Shiba, Yoko; Xavier, Charles P.; Rubin, Jeffrey S.] NCI, Cellular & Mol Biol Lab, Bethesda, MD 20892 USA. [Westlake, Christopher J.] NCI, Lab Cell & Dev Signaling, Frederick, MD 21702 USA. [Gao, Bo; Yang, Yingzi] NHGRI, Genet Dis Res Branch, Bethesda, MD 20892 USA. [Bharti, Kapil] NEI, Ophthalm Genet & Visual Funct Branch, Bethesda, MD 20892 USA. [Pazour, Gregory J.] Univ Massachusetts, Sch Med, Program Mol Med, Worcester, MA 01605 USA. RP Rubin, JS (reprint author), NCI, Cellular & Mol Biol Lab, Bldg 37, Bethesda, MD 20892 USA. EM rubinj@mail.nih.gov FU National Institutes of Health [GM060992]; Intramural Research Program of the National Institutes of Health, National Cancer Institute FX We thank Eli Lilly for providing the CK1 delta monoclonal antibody 128A and Irina Kaverina and Sean Munro, respectively, for providing the plasmids encoding AKAP450/159-463-GFP and GFPAKAP450/3643-3908. We also appreciate comments on the manuscript from Sergei Sokol and Kyeongmi Kim (Mount Sinai School of Medicine, New York, NY). This research was supported by Grant GM060992 from the National Institutes of Health to G.J.P. and the Intramural Research Program of the National Institutes of Health, National Cancer Institute. NR 49 TC 10 Z9 11 U1 0 U2 3 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 EI 1939-4586 J9 MOL BIOL CELL JI Mol. Biol. Cell PD MAY 15 PY 2014 VL 25 IS 10 BP 1629 EP 1640 DI 10.1091/mbc.E13-10-0598 PG 12 WC Cell Biology SC Cell Biology GA AM2AP UT WOS:000339650800009 PM 24648492 ER PT J AU Poletto, M Lirussi, L Wilson, DM Tell, G AF Poletto, Mattia Lirussi, Lisa Wilson, David M., III Tell, Gianluca TI Nucleophosmin modulates stability, activity, and nucleolar accumulation of base excision repair proteins SO MOLECULAR BIOLOGY OF THE CELL LA English DT Article ID RNA QUALITY-CONTROL; DNA-DAMAGE; LYSINE RESIDUES; CELLS; P53; TRANSCRIPTION; INTERACTS; STABILIZATION; LOCALIZATION; DAUNORUBICIN AB Nucleophosmin (NPM1) is a multifunctional protein that controls cell growth and genome stability via a mechanism that involves nucleolar-cytoplasmic shuttling. It is clear that NPM1 also contributes to the DNA damage response, yet its exact function is poorly understood. We recently linked NPM1 expression to the functional activation of the major abasic endonuclease in mammalian base excision repair (BER), apurinic/apyrimidinic endonuclease 1 (APE1). Here we unveil a novel role for NPM1 as a modulator of the whole BER pathway by 1) controlling BER protein levels, 2) regulating total BER capacity, and 3) modulating the nucleolar localization of several BER enzymes. We find that cell treatment with the genotoxin cisplatin leads to concurrent relocalization of NPM1 and BER components from nucleoli to the nucleoplasm, and cellular experiments targeting APE1 suggest a role for the redistribution of nucleolar BER factors in determining cisplatin toxicity. Finally, based on the use of APE1 as a representative protein of the BER pathway, our data suggest a function for BER proteins in the regulation of ribogenesis. C1 [Poletto, Mattia; Lirussi, Lisa; Tell, Gianluca] Univ Udine, Dept Med & Biol Sci, I-33100 Udine, Italy. [Wilson, David M., III] NIA, Lab Mol Gerontol, Intramural Res Program, NIH, Baltimore, MD 21224 USA. RP Tell, G (reprint author), Univ Udine, Dept Med & Biol Sci, I-33100 Udine, Italy. EM gianluca.tell@uniud.it OI Tell, Gianluca/0000-0001-8845-6448 FU Associazione Italiana per la Ricerca sul Cancro [IG10269, IG14038]; Intramural Research Program at the National Institutes of Health, National Institute on Aging FX We acknowledge Bruce Demple and Alex Pines for critical comments on the manuscript and the National Center for Advancing Translational Sciences for providing the APE1-specific inhibitor (compound # 3). This work was supported by grants from the Associazione Italiana per la Ricerca sul Cancro (IG10269 and IG14038) to G. T. and in part by the Intramural Research Program at the National Institutes of Health, National Institute on Aging, to D. M. W. NR 45 TC 14 Z9 14 U1 0 U2 6 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 EI 1939-4586 J9 MOL BIOL CELL JI Mol. Biol. Cell PD MAY 15 PY 2014 VL 25 IS 10 BP 1641 EP 1652 DI 10.1091/mbc.E13-12-0717 PG 12 WC Cell Biology SC Cell Biology GA AM2AP UT WOS:000339650800010 PM 24648491 ER PT J AU Ball, CB Rodriguez, KF Stumpo, DJ Ribeiro-Neto, F Korach, KS Blackshear, PJ Birnbaumer, L Ramos, SBV AF Ball, Christopher B. Rodriguez, Karina F. Stumpo, Deborah J. Ribeiro-Neto, Fernando Korach, Kenneth S. Blackshear, Perry J. Birnbaumer, Lutz Ramos, Silvia B. V. TI The RNA-Binding Protein, ZFP36L2, Influences Ovulation and Oocyte Maturation SO PLOS ONE LA English DT Article ID LUTEINIZING-HORMONE RECEPTOR; HUMAN CHORIONIC-GONADOTROPIN; EARLY EMBRYONIC-DEVELOPMENT; MESSENGER-RIBONUCLEIC-ACID; OVARIAN FOLLICULAR-FLUID; TO-CELL COMMUNICATION; MEIOTIC ARREST; CYCLIC-AMP; IN-VITRO; GRAAFIAN-FOLLICLES AB ZFP36L2 protein destabilizes AU-rich element-containing transcripts and has been implicated in female fertility. In the C57BL/6NTac mouse, a mutation in Zfp36l2 that results in the decreased expression of a form of ZFP36L2 in which the 29 N-terminal amino acid residues have been deleted, Delta N-ZFP36L2, leads to fertilized eggs that arrest at the two-cell stage. Interestingly, homozygous Delta N-Zfp36l2 females in the C57BL/6NTac strain release 40% fewer eggs than the WT littermates (Ramos et al., 2004), suggesting an additional defect in ovulation and/or oocyte maturation. Curiously, the same Delta N-Zfp36l2 mutation into the SV129 strain resulted in anovulation, prompting us to investigate a potential problem in ovulation and oocyte maturation. Remarkably, only 20% of Delta N-Zfp36l2 oocytes in the 129S6/SvEvTac strain matured ex vivo, suggesting a defect on the oocyte meiotic maturation process. Treatment of Delta N-Zfp36l2 oocytes with a PKA inhibitor partially rescued the meiotic arrested oocytes. Furthermore, cAMP levels were increased in Delta N-Zfp36l2 oocytes, linking the cAMP/PKA pathway and Delta N-Zfp36l2 with meiotic arrest. Since ovulation and oocyte maturation are both triggered by LHR signaling, the downstream pathway was investigated. Adenylyl cyclase activity was increased in Delta N-Zfp36l2 ovaries only upon LH stimulation. Moreover, we discovered that ZFP36L2 interacts with the 3'UTR of LHR mRNA and that decreased expression levels of Zfp36l2 correlates with higher levels of LHR mRNA in synchronized ovaries. Furthermore, overexpression of ZFP36L2 decreases the endogenous expression of LHR mRNA in a cell line. Therefore, we propose that lack of the physiological down regulation of LHR mRNA levels by ZFP36L2 in the ovaries is associated with anovulation and oocyte meiotic arrest. C1 [Ball, Christopher B.; Ramos, Silvia B. V.] Univ N Carolina, Sch Med, Dept Obstet & Gynecol, Div Reprod Endocrinol & Infertil, Chapel Hill, NC 27515 USA. [Rodriguez, Karina F.; Korach, Kenneth S.] NIEHS, Lab Reprod & Dev Toxicol, NIH, Dept Hlth & Human Serv, Res Triangle Pk, NC 27709 USA. [Stumpo, Deborah J.; Ribeiro-Neto, Fernando; Blackshear, Perry J.] NIEHS, Lab Signal Transduct, NIH, Dept Hlth & Human Serv, Res Triangle Pk, NC 27709 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. [Birnbaumer, Lutz] NIEHS, Neurobiol Lab, NIH, Dept Hlth & Human Serv, Res Triangle Pk, NC 27709 USA. RP Ramos, SBV (reprint author), Univ N Carolina, Sch Med, Dept Obstet & Gynecol, Div Reprod Endocrinol & Infertil, Chapel Hill, NC 27515 USA. EM sramos@med.unc.edu OI Korach, Kenneth/0000-0002-7765-418X FU National Institutes of Health [K08 HD069597]; Institute for Biological Recognition and Catalysis, Inc.; UNC TraCS [550KR11128]; NIH, NIEHS [Z01-ES70065, Z01-ES090080-15, Z01-ES101643] FX This work was supported by the National Institutes of Health Grant K08 HD069597 (to S. B. R.); Institute for Biological Recognition and Catalysis, Inc. (to S. B. R.), UNC TraCS grant # 550KR11128 (to S. B. R.) and by the Intramural Research Program of the NIH, NIEHS Z01-ES70065 (to K. S. K.), Z01-ES090080-15 (to P.J.B.) and Z01-ES101643 (to L. B.). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 48 TC 2 Z9 2 U1 0 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 MAY 15 PY 2014 VL 9 IS 5 AR e97324 DI 10.1371/journal.pone.0097324 PG 12 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA AI3UI UT WOS:000336789500049 PM 24830504 ER PT J AU Moslehi, R Ambroggio, X Nagarajan, V Kumar, A Dzutsev, A AF Moslehi, Roxana Ambroggio, Xavier Nagarajan, Vijayaraj Kumar, Anil Dzutsev, Amiran TI Nucleotide excision repair/transcription gene defects in the fetus and impaired TFIIH-mediated function in transcription in placenta leading to preeclampsia SO BMC GENOMICS LA English DT Article ID DNA-REPAIR; XERODERMA-PIGMENTOSUM; COCKAYNE-SYNDROME; INTERACTION NETWORKS; CLINICAL-FEATURES; XPD GENE; TRICHOTHIODYSTROPHY; MUTATIONS; EXPRESSION; DEFICIENT AB Background: Preeclampsia is a significant cause of maternal and fetal mortality and morbidity worldwide. We previously reported associations between trichothiodystrophy (TTD) nucleotide excision repair (NER) and transcription gene mutations in the fetus and the risk of gestational complications including preeclampsia. TTD NER/transcription genes, XPD, XPB and TTD-A, code for subunits of Transcription Factor (TF) IIH. Interpreting XPD mutations in the context of available biochemical data led us to propose adverse effects on CDK-activating kinase (CAK) subunit of TFIIH and TFIIH-mediated functions as a relevant mechanism in preeclampsia. In order to gain deeper insight into the underlying biologic mechanisms involving TFIIH-mediated functions in placenta, we analyzed NER/transcription and global gene expression profiles of normal and preeclamptic placentas and studied gene regulatory networks. Results: We found high expression of TTD NER/transcription genes in normal human placenta, above the mean of their expression in all organs. XPD and XPB were consistently expressed from 14 to 40 weeks gestation while expression of TTD-A was strongly negatively correlated (r = -0.7, P < 0.0001) with gestational age. Analysis of gene expression patterns of placentas from a case-control study of preeclampsia using Algorithm for Reconstruction of Accurate Cellular Networks (ARACNE) revealed GTF2E1, a component of TFIIE which modulates TFIIH, among major regulators of differentially-expressed genes in preeclampsia. The basal transcription pathway was among the largest dysregulated protein-protein interaction networks in this preeclampsia dataset. Within the basal transcription pathway, significantly down-regulated genes besides GTF2E1 included those coding for the CAK complex of TFIIH, namely CDK7, CCNH, and MNAT1. Analysis of other relevant gene expression and gene regulatory network data also underscored the involvement of transcription pathways and identified JUNB and JUND (components of transcription factor AP-1) as transcription regulators of the network involving the TTD genes, GTF2E1, and selected gene regulators implicated in preeclampsia. Conclusions: Our results indicate that TTD NER/transcription genes are expressed in placenta during gestational periods critical to preeclampsia development. Our overall findings suggest that impairment of TFIIH-mediated function in transcription in placenta is a likely mechanism leading to preeclampsia and provide etiologic clues which may be translated into therapeutic and preventive measures. C1 [Moslehi, Roxana; Kumar, Anil] SUNY Albany, Sch Publ Hlth, Dept Epidemiol & Biostat, Rensselaer, NY 12144 USA. [Moslehi, Roxana] SUNY Albany, Canc Res Ctr, Rensselaer, NY 12144 USA. [Ambroggio, Xavier] Rosetta Design Grp LLC, Burlington, VT 05401 USA. [Nagarajan, Vijayaraj] NIAID, Bioinformat & Computat Biosci Branch, Off Cyber Infrastruct & Computat Biol, NIH, Bethesda, MD 20814 USA. [Dzutsev, Amiran] Leidos Biomed Res Inc, Frederick, MD 21701 USA. [Dzutsev, Amiran] NCI, Canc & Inflammat Program, NIH, Frederick, MD 21702 USA. RP Moslehi, R (reprint author), SUNY Albany, Sch Publ Hlth, Dept Epidemiol & Biostat, Rensselaer, NY 12144 USA. EM rmoslehi@albany.edu; dzutseva@mail.nih.gov FU Center for Social and Demographic Analysis (CSDA) at University at Albany from NICHD [R24 HD044943]; Intramural Research Program of the NIH; National Cancer Institute FX The authors are grateful to Drs. James L. Mills and Caroline Signore at the Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD), NIH for their significant contributions. Technical support provided by Mr. H. Martinez at University at Albany is appreciated. This study was supported in part by a grant to the Center for Social and Demographic Analysis (CSDA) at University at Albany from NICHD (R24 HD044943) and a research award to RM from CSDA. This research was also supported in part by the Intramural Research Program of the NIH, National Cancer Institute. Opinions, findings and conclusions expressed here are those of the authors and do not necessarily reflect the views of the funding agencies. The content of this publication does not necessarily reflect the 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 49 TC 2 Z9 2 U1 4 U2 10 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 MAY 15 PY 2014 VL 15 AR 373 DI 10.1186/1471-2164-15-373 PG 11 WC Biotechnology & Applied Microbiology; Genetics & Heredity SC Biotechnology & Applied Microbiology; Genetics & Heredity GA AI2HC UT WOS:000336677300002 PM 24885447 ER PT J AU Jia, JP Bosley, AD Thompson, A Hoskins, JW Cheuk, A Collins, I Parikh, H Xiao, Z Ylaya, K Dzyadyk, M Cozen, W Hernandez, BY Lynch, CF Loncarek, J Altekruse, SF Zhang, LZ Westlake, CJ Factor, VM Thorgeirsson, S Bamlet, WR Hewitt, SM Petersen, GM Andresson, T Amundadottir, LT AF Jia, Jinping Bosley, Allen D. Thompson, Abbey Hoskins, Jason W. Cheuk, Adam Collins, Irene Parikh, Hemang Xiao, Zhen Ylaya, Kris Dzyadyk, Marta Cozen, Wendy Hernandez, Brenda Y. Lynch, Charles F. Loncarek, Jadranka Altekruse, Sean F. Zhang, Lizhi Westlake, Christopher J. Factor, Valentina M. Thorgeirsson, Snorri Bamlet, William R. Hewitt, Stephen M. Petersen, Gloria M. Andresson, Thorkell Amundadottir, Laufey T. TI CLPTM1L Promotes Growth and Enhances Aneuploidy in Pancreatic Cancer Cells SO CANCER RESEARCH LA English DT Article ID GENOME-WIDE ASSOCIATION; NONMUSCLE MYOSIN-II; LUNG-CANCER; SUSCEPTIBILITY LOCI; TERT-CLPTM1L LOCUS; VARIANTS; RISK; 5P15.33; TERT; METAANALYSIS AB Genome-wide association studies (GWAS) of 10 different cancers have identified pleiotropic cancer predisposition loci across a region of chromosome 5p15.33 that includes the TERT and CLPTM1L genes. Of these, susceptibility alleles for pancreatic cancer have mapped to the CLPTM1L gene, thus prompting an investigation of the function of CLPTM1L in the pancreas. Immunofluorescence analysis indicated that CLPTM1L localized to the endoplasmic reticulum where it is likely embedded in the membrane, in accord with multiple predicted transmembrane domains. Overexpression of CLPTM1L enhanced growth of pancreatic cancer cells in vitro (1.3-1.5-fold; P-DAY7 < 0.003) and in vivo (3.46-fold; P-DAY68 = 0.039), suggesting a role in tumor growth; this effect was abrogated by deletion of two hydrophilic domains. Affinity purification followed by mass spectrometry identified an interaction between CLPTM1L and non-muscle myosin II (NMM-II), a protein involved in maintaining cell shape, migration, and cytokinesis. The two proteins colocalized in the cytoplasm and, after treatment with a DNA-damaging agent, at the centrosomes. Overexpression of CLPTM1L and depletion of NMM-II induced aneuploidy, indicating that CLPTM1L may interfere with normal NMM-II function in regulating cytokinesis. Immunohistochemical analysis revealed enhanced staining of CLPTM1L in human pancreatic ductal adenocarcinoma (n = 378) as compared with normal pancreatic tissue samples (n 17; P = 1.7 x 10(-4)). Our results suggest that CLPTM1L functions as a growth-promoting gene in the pancreas and that overexpression may lead to an abrogation of normal cytokinesis, indicating that it should be considered as a plausible candidate gene that could explain the effect of pancreatic cancer susceptibility alleles on chr5p15.33. (C)2014 AACR. C1 [Jia, Jinping; Thompson, Abbey; Hoskins, Jason W.; Collins, Irene; Parikh, Hemang; Dzyadyk, Marta; Amundadottir, Laufey T.] NCI, Lab Translat Genom, Div Canc Epidemiol & Genet, NIH,Dept Hlth & Human Serv, Bethesda, MD 20892 USA. [Cheuk, Adam] NCI, Pediat Oncol Branch, NIH, Dept Hlth & Human Serv, Bethesda, MD 20892 USA. [Ylaya, Kris; Hewitt, Stephen M.] NCI, Pathol Lab, NIH, Dept Hlth & Human Serv, Bethesda, MD 20892 USA. [Altekruse, Sean F.] NCI, Div Canc Control & Populat Sci, NIH, Dept Hlth & Human Serv, Bethesda, MD 20892 USA. [Factor, Valentina M.; Thorgeirsson, Snorri] NCI, Expt Carcinogenesis Lab, NIH, Dept Hlth & Human Serv, Bethesda, MD 20892 USA. [Bosley, Allen D.; Xiao, Zhen; Andresson, Thorkell] NCI, Lab Prote & Analyt Technol, Leidos Biomed Res, Frederick Natl Lab Canc Res, Frederick, MD 21701 USA. [Loncarek, Jadranka] NCI, Lab Prot Dynam & Signaling, Frederick, MD 21701 USA. [Westlake, Christopher J.] NCI, Lab Cell & Dev Signaling, Frederick, MD 21701 USA. [Cozen, Wendy] Univ So Calif, Keck Sch Med, Los Angeles, CA 90033 USA. [Hernandez, Brenda Y.] Univ Hawaii, Ctr Canc, Honolulu, HI 96822 USA. [Lynch, Charles F.] Univ Iowa, Coll Publ Hlth, Dept Epidemiol, Iowa City, IA USA. [Zhang, Lizhi; Bamlet, William R.; Petersen, Gloria M.] Mayo Clin, Dept Hlth Sci Res, Rochester, MN USA. RP Amundadottir, LT (reprint author), NIH, Lab Translat Genom, Div Canc Epidemiol & Genet, 8717 Grovemont Circle, Gaithersburg, MD 20877 USA. EM amundadottirl@mail.nih.gov RI Amundadottir, Laufey/L-7656-2016; OI Amundadottir, Laufey/0000-0003-1859-8971; Hewitt, Stephen/0000-0001-8283-1788; Hoskins, Jason/0000-0001-6944-1996 FU Intramural Research Program of the Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health (NIH) [HHSN2612 00800001E] FX This study was supported in part by the Intramural Research Program of the Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health (NIH) under Contract No. HHSN2612 00800001E. NR 48 TC 18 Z9 18 U1 0 U2 9 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 MAY 15 PY 2014 VL 74 IS 10 BP 2785 EP 2795 DI 10.1158/0008-5472.CAN-13-3176 PG 11 WC Oncology SC Oncology GA AI2WW UT WOS:000336720700014 PM 24648346 ER PT J AU Bates, SE AF Bates, Susan E. TI The Language of Pharmacodynamics SO CLINICAL CANCER RESEARCH LA English DT Editorial Material C1 NCI, Bethesda, MD 20892 USA. RP Bates, SE (reprint author), NCI, Bethesda, MD 20892 USA. FU Intramural NIH HHS [ZIA BC010622-10] NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1078-0432 EI 1557-3265 J9 CLIN CANCER RES JI Clin. Cancer Res. PD MAY 15 PY 2014 VL 20 IS 10 BP 2524 EP 2524 DI 10.1158/1078-0432.CCR-14-0739 PG 1 WC Oncology SC Oncology GA AI2WU UT WOS:000336720200004 PM 24831274 ER PT J AU Figg, WD Newell, DR AF Figg, William Douglas Newell, David R. TI Pharmacologic Biomarkers in the Development of Stratified Cancer Medicine SO CLINICAL CANCER RESEARCH LA English DT Article ID CIRCULATING TUMOR DNA; SURROGATE END-POINTS; ACQUIRED-RESISTANCE; DRUG DEVELOPMENT; VALIDATION; TOXICITY; ONCOLOGY; UTILITY; CELLS AB Clinical pharmacologic research plays a vital role in cancer drug development. In recent years, biomarker studies have become integral to this process, specifically the use of pharmacologic biomarkers in the development of targeted therapies and their translation to clinical practice. In this overview, we discuss the validation of pharmacodynamics (PD) biomarkers and highlight the circulating tumor DNA as a promising cancer biomarker to illustrate how PD 'biomarkers can be powerful tools for guiding treatment strategies. We provide insights into PD biomarker approaches for future development of novel therapies and their role in cancer medicine. (C) 2014 AACR. C1 [Figg, William Douglas] NCI, Clin Pharmacol Program, Off Clin Director,Ctr Canc Res,NIH, Mol Pharmacol Sect & Genitourinary Malignancies B, Bethesda, MD 20892 USA. [Newell, David R.] Newcastle Univ, Northern Inst Canc Res, Newcastle Upon Tyne, Tyne & Wear, England. RP Figg, WD (reprint author), NCI, NIH, 10 Ctr Dr,9000 Rockville Pike,Bldg 10 Room 5A01, Bethesda, MD 20892 USA. EM figgw@helix.nih.gov; herbie.newell@ncl.ac.uk RI Figg Sr, William/M-2411-2016 FU Astex Pharmaceuticals FX D.R. Newell reports receiving commercial research grants and speakers bureau honoraria from Astex Pharmaceuticals and is a consultant/advisory board member for Astex Pharmaceuticals. No potential conflicts of interest were disclosed by the other author. NR 29 TC 2 Z9 2 U1 0 U2 10 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 MAY 15 PY 2014 VL 20 IS 10 BP 2525 EP 2529 DI 10.1158/1078-0432.CCR-14-0511 PG 5 WC Oncology SC Oncology GA AI2WU UT WOS:000336720200005 PM 24831275 ER PT J AU Kinders, R Ferry-Galow, K Wang, LH Srivastava, AK Ji, JP Parchment, RE AF Kinders, Robert Ferry-Galow, Kate Wang, Lihua Srivastava, Apurva K. Ji, Jiuping (Jay) Parchment, Ralph E. TI Implementation of Validated Pharmacodynamic Assays in Multiple Laboratories: Challenges, Successes, and Limitations SO CLINICAL CANCER RESEARCH LA English DT Article ID CIRCULATING TUMOR-CELLS; ADP-RIBOSE POLYMERASE; 0 CLINICAL-TRIAL; BREAST-CANCER; DEPENDENT APOPTOSIS; COLORECTAL-CANCER; SIGNALING PATHWAY; DOWN-REGULATION; PROTEIN FAMILY; LEUKEMIA-CELLS AB There is a "life cycle" of pharmacodynamic (PD) biomarker assays that guides the development and clinical implementation in our laboratories. The well-recognized elements of analytical assay validation and demonstration of fitness-for-purpose of the biomarker, specimen collection, handling, and assay methods are only a part of the required activities. Assay transfer across laboratories and testing on actual human clinical specimens are vital for understanding assay performance and robustness. In our experience, this patient specimen-centered approach has required assay method modifications, some unexpected, but which were critical to successful implementation in clinical trials. In addition, dispersing assays throughout the National Cancer Institute's clinical trials network has required the development of calibrator and control materials as well as formal training courses for smooth implementation. One measure of success of this approach has been that a number of the assays developed at NCI's Frederick National Laboratory have ultimately reached the stage of commercialization, enabling wide accessibility of the PD biomarker assays by the research community. C1 [Kinders, Robert; Ferry-Galow, Kate; Wang, Lihua; Srivastava, Apurva K.; Parchment, Ralph E.] Frederick Natl Lab Canc Res, Lab Human Toxicol & Pharmacol, Frederick, MD USA. [Ji, Jiuping (Jay)] Frederick Natl Lab Canc Res, Appl Dev Res Directorate, Natl Canc Target Validat Lab, Frederick, MD USA. [Ji, Jiuping (Jay)] Leidos Biomed Res Inc, Frederick, MD 21702 USA. RP Kinders, R (reprint author), Leidos Biomed Res Inc, Appl Dev Directorate, Lab Human Toxicol & Pharmacol, Frederick Natl Lab Canc Res, Frederick, MD 21702 USA. EM kindersr@mail.nih.gov FU Intramural NIH HHS [Z99 CA999999] NR 46 TC 5 Z9 5 U1 2 U2 5 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 MAY 15 PY 2014 VL 20 IS 10 BP 2578 EP 2586 DI 10.1158/1078-0432.CCR-14-0476 PG 9 WC Oncology SC Oncology GA AI2WU UT WOS:000336720200010 PM 24831280 ER PT J AU Bartlett, EK Fetsch, PA Filie, AC Abati, A Steinberg, SM Wunderlich, JR White, DE Stephens, DJ Marincola, FM Rosenberg, SA Kammula, US AF Bartlett, Edmund K. Fetsch, Patricia A. Filie, Armando C. Abati, Andrea Steinberg, Seth M. Wunderlich, John R. White, Donald E. Stephens, Daniel J. Marincola, Francesco M. Rosenberg, Steven A. Kammula, Udai S. TI Human Melanoma Metastases Demonstrate Nonstochastic Site-Specific Antigen Heterogeneity That Correlates with T-cell Infiltration SO CLINICAL CANCER RESEARCH LA English DT Article ID FINE-NEEDLE-ASPIRATION; MALIGNANT-MELANOMA; CANCER METASTASIS; VISCERAL METASTASES; IN-VIVO; TUMOR; EXPRESSION; IMMUNOTHERAPY; LYMPHOCYTES; TYROSINASE AB Purpose: Metastasis heterogeneity presents a significant obstacle to the development of targeted cancer therapeutics. In this study, we sought to establish from a large series of human melanoma metastases whether there exists a determined pattern in tumor cellular heterogeneity that may guide the development of future targeted immunotherapies. Experimental Design: From a cohort of 1,514 patients with metastatic melanoma, biopsies were procured over a 17-year period from 3,086 metastatic tumors involving various anatomic sites. To allow specific tumor cell profiling, we used established immunohistochemical methods to perform semiquantitative assessment for a panel of prototypic melanocyte differentiation antigens (MDA), including gp100, MART-1, and tyrosinase. To gain insight into the endogenous host immune response against these tumors, we further characterized tumor cell expression of MHC I and MHC II and, also, the concomitant CD4(+) and CD8(+) T-cell infiltrate. Results: Tumor cell profiling for MDA expression demonstrated an anatomic site-specific pattern of antigen expression that was highest in brain, intermediate in soft tissues/lymph nodes, and lowest in visceral metastases. Hierarchical clustering analysis supported that melanoma metastases have a phylogenetically determined, rather than a stochastic, pattern of antigen expression that varies by anatomic site. Furthermore, tyrosinase expression was more frequently lost in metastatic sites outside of the brain and was uniquely correlated with both endogenous CD8(+) and CD4(+) T-cell infiltrates. Conclusion: Site-specific antigen heterogeneity represents a novel attribute for human melanoma metastases that should be considered in future therapy development and when assessing the responsiveness to antigen-specific immunotherapies. (C) 2014 AACR. C1 [Bartlett, Edmund K.; Wunderlich, John R.; White, Donald E.; Stephens, Daniel J.; Rosenberg, Steven A.; Kammula, Udai S.] NCI, Surg Branch, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. [Fetsch, Patricia A.; Filie, Armando C.; Abati, Andrea] NCI, Cytopathol Sect, Pathol Lab, Ctr Canc Res,NIH, Bethesda, MD 20892 USA. [Steinberg, Seth M.] NCI, Biostat & Data Management Sect, Ctr Canc Res, Ctr Canc Res,NIH, Bethesda, MD 20892 USA. [Marincola, Francesco M.] Sidra Med & Res Ctr, Doha, Qatar. RP Kammula, US (reprint author), NCI, Surg Branch, Ctr Canc Res, 10 Ctr Dr,Bldg 10 Hatfield CRC,Rm 3-5930, Bethesda, MD 20892 USA. EM udai_kammula@nih.gov OI Bartlett, Edmund/0000-0002-0923-153X FU Intramural Research Program of the NIH, NCI, Center for Cancer Research FX This research was supported by the Intramural Research Program of the NIH, NCI, Center for Cancer Research. NR 38 TC 6 Z9 6 U1 1 U2 4 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 MAY 15 PY 2014 VL 20 IS 10 BP 2607 EP 2616 DI 10.1158/1078-0432.CCR-13-2690 PG 10 WC Oncology SC Oncology GA AI2WU UT WOS:000336720200013 PM 24647571 ER PT J AU Palmieri, D Duchnowska, R Woditschka, S Hua, E Qian, YZ Biernat, W Sosinska-Mielcarek, K Gril, B Stark, AM Hewitt, SM Liewehr, DJ Steinberg, SM Jassem, J Steeg, PS AF Palmieri, Diane Duchnowska, Renata Woditschka, Stephan Hua, Emily Qian, Yongzhen Biernat, Wojciech Sosinska-Mielcarek, Katarzyna Gril, Brunilde Stark, Andreas M. Hewitt, Stephen M. Liewehr, David J. Steinberg, Seth M. Jassem, Jacek Steeg, Patricia S. TI Profound Prevention of Experimental Brain Metastases of Breast Cancer by Temozolomide in an MGMT-Dependent Manner SO CLINICAL CANCER RESEARCH LA English DT Article ID CELL LUNG-CANCER; NERVOUS-SYSTEM METASTASES; PHASE-II TRIAL; LOW-GRADE GLIOMAS; SOLID TUMORS; IN-VIVO; CLINICAL-TRIALS; BLOOD-BRAIN; CHEMOTHERAPY; LAPATINIB AB Purpose: Brain metastases of breast cancer cause neurocognitive damage and are incurable. We evaluated a role for temozolomide in the prevention of brain metastases of breast cancer in experimental brain metastasis models. Experimental Design: Temozolomide was administered in mice following earlier injection of braintropic HER2-positive JIMT-1-BR3 and triple-negative 231-BR-EGFP sublines, the latter with and without expression of O-6-methylguanine-DNA methyltransferase (MGMT). In addition, the percentage of MGMT-positive tumor cells in 62 patient-matched sets of breast cancer primary tumors and resected brain metastases was determined immunohistochemically. Results: Temozolomide, when dosed at 50, 25, 10, or 5 mg/kg, 5 days per week, beginning 3 days after inoculation, completely prevented the formation of experimental brain metastases from MGMT-negative 231-BR-EGFP cells. At a 1 mg/kg dose, temozolomide prevented 68% of large brain metastases, and was ineffective at a dose of 0.5 mg/kg. When the 50 mg/kg dose was administered beginning on days 18 or 24, temozolomide efficacy was reduced or absent. Temozolomide was ineffective at preventing brain metastases in MGMT-transduced 231-BR-EGFP and MGMT-expressing JIMT-1-BR3 sublines. In 62 patient-matched sets of primary breast tumors and resected brain metastases, 43.5% of the specimens had concordant low MGMT expression, whereas in another 14.5% of sets high MGMT staining in the primary tumor corresponded with low staining in the brain metastasis. Conclusions: Temozolomide profoundly prevented the outgrowth of experimental brain metastases of breast cancer in an MGMT-dependent manner. These data provide compelling rationale for investigating the preventive efficacy of temozolomide in a clinical setting. C1 [Palmieri, Diane; Woditschka, Stephan; Hua, Emily; Gril, Brunilde; Steeg, Patricia S.] NCI, Womens Malignancies Branch, NIH, Bethesda, MD 20892 USA. [Hewitt, Stephen M.; Jassem, Jacek] NCI, Pathol Lab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. [Liewehr, David J.; Steinberg, Seth M.] NCI, Biostat & Data Management Sect, NIH, Bethesda, MD 20892 USA. [Qian, Yongzhen] NCI, Lab Anim Sci Program, SAIC Frederick, NIH, Frederick, MD 21701 USA. [Duchnowska, Renata] Mil Inst Med, Dept Oncol, Warsaw, Poland. [Biernat, Wojciech] Med Univ, Dept Pathomorphol, Gdansk, Poland. [Jassem, Jacek] Med Univ, Dept Oncol & Radiotherapy, Gdansk, Poland. [Sosinska-Mielcarek, Katarzyna] Reg Canc Ctr, Gdansk, Poland. [Stark, Andreas M.] Klin Neurochirurg UKSH Campus Kiel, Kiel, Germany. RP Steeg, PS (reprint author), NCI, 37-1126 NIH, Bethesda, MD 20892 USA. EM steegp@mail.nih.gov RI Palmieri, Diane/B-4258-2015; OI Hewitt, Stephen/0000-0001-8283-1788 FU Intramural program of the National Cancer Institute; U.S. Department of Defense Breast Cancer Research Program [W81 XWH-062-0033]; Intramural grant of the Medical University of Gdansk (Gdansk, Poland) [ST-51] FX This work was supported by the Intramural program of the National Cancer Institute and U.S. Department of Defense Breast Cancer Research Program, grant number: W81 XWH-062-0033, and an Intramural grant of the Medical University of Gdansk (Gdansk, Poland), grant number ST-51. NR 51 TC 12 Z9 12 U1 0 U2 5 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 MAY 15 PY 2014 VL 20 IS 10 BP 2727 EP 2739 DI 10.1158/1078-0432.CCR-13-2588 PG 13 WC Oncology SC Oncology GA AI2WU UT WOS:000336720200024 PM 24634373 ER PT J AU Lu, X Mazur, SJ Lin, T Appella, E Xu, Y AF Lu, X. Mazur, S. J. Lin, T. Appella, E. Xu, Y. TI The pluripotency factor nanog promotes breast cancer tumorigenesis and metastasis SO ONCOGENE LA English DT Article DE nanog; breast cancer; tumorigenesis; metastasis ID EMBRYONIC STEM-CELLS; GENE-EXPRESSION; SIGNALING PATHWAYS; TUMOR-DEVELOPMENT; MAMMARY-GLAND; ES CELLS; GENOME; OCT4; MIGRATION; CARCINOMA AB Nanog is a transcription factor required for maintaining the pluripotency of embryonic stem cells, and is not expressed in most normal adult tissues. However, recent studies have indicated that Nanog is overexpressed in many types of human cancers, including breast cancer. To elucidate the physiological roles of Nanog in tumorigenesis, we developed an inducible Nanog transgenic mouse model, in which the expression of Nanog in adult tissues can be induced via LoxP/Cre-mediated deletion. Our findings indicate that overexpression of Nanog in the mammary gland is not sufficient to induce mammary tumor. However, when coexpressed with Wnt-1 in the mouse mammary gland, it promotes mammary tumorigenesis and metastasis. In this context, Nanog promotes the migration and invasion of breast cancer cells. Microarray analysis has shown that the ectopic expression of Nanog deregulates the expression of numerous genes associated with tumorigenesis and metastasis, such as the PDGFR alpha gene. Our findings demonstrate the involvement of Nanog in breast cancer metastasis, and provide the basis for the reported correlation between Nanog expression and poor prognosis of human breast cancer patients. As Nanog is not expressed in most adult tissues, these findings identify Nanog as a potential therapeutic target in the treatment of Nanog-expressing metastatic breast cancer. C1 [Lu, X.; Xu, Y.] Univ Calif San Diego, Div Biol Sci, La Jolla, CA 92093 USA. [Mazur, S. J.; Appella, E.] NCI, Lab Cell Biol, NIH, Bethesda, MD 20892 USA. [Lin, T.] Guangdong Prov Acad Chinese Med Sci, Ctr Regenerat Med & Translat Med, Guangzhou, Guangdong, Peoples R China. RP Xu, Y (reprint author), Univ Calif San Diego, Div Biol Sci, 9500 Gilman Dr, La Jolla, CA 92093 USA. EM yangxu@ucsd.edu RI Lin, Tongxiang/I-4695-2013 OI Lin, Tongxiang/0000-0001-7033-6982 FU NIH [CA94254, CA124834]; Intramural Research Program of the National Cancer Institute, National Institutes of Health FX We thank Y Li for providing the Wnt-1 transgenic mice. This work was supported by NIH grants (CA94254 and CA124834) to YX and by the Intramural Research Program of the National Cancer Institute, National Institutes of Health. NR 52 TC 31 Z9 33 U1 2 U2 9 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 MAY 15 PY 2014 VL 33 IS 20 BP 2655 EP 2664 DI 10.1038/onc.2013.209 PG 10 WC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity GA AH9YT UT WOS:000336502700011 PM 23770853 ER PT J AU Selker, HP Udelson, JE Massaro, JM Ruthazer, R D'Agostino, RB Griffith, JL Sheehan, PR Desvigne-Nickens, P Rosenberg, Y Tian, X Vickery, EM Atkins, JM Aufderheide, TP Sayah, AJ Pirrallo, RG Levy, MK Richards, ME Braude, DA Doyle, DD Frascone, RJ Kosiak, DJ Leaming, JM Van Gelder, CM Walter, GP Wayne, MA Woolard, RH Beshansky, JR AF Selker, Harry P. a Udelson, James E. Massaro, Joseph M. Ruthazer, Robin D'Agostino, Ralph B. Griffith, John L. Sheehan, Patricia R. Desvigne-Nickens, Patrice Rosenberg, Yves Tian, Xin Vickery, Ellen M. Atkins, James M. Aufderheide, Tom P. Sayah, Assaad J. Pirrallo, Ronald G. Levy, Michael K. Richards, Michael E. Braude, Darren A. Doyle, Delanor D. Frascone, Ralph J. Kosiak, Donald J. Leaming, James M. Van Gelder, Carin M. Walter, Gert-Paul Wayne, Marvin A. Woolard, Robert H. Beshansky, Joni R. TI One-Year Outcomes of Out-of-Hospital Administration of Intravenous Glucose, Insulin, and Potassium (GIK) in Patients With Suspected Acute Coronary Syndromes (from the IMMEDIATE [Immediate Myocardial Metabolic Enhancement During Initial Assessment and Treatment in Emergency Care] Trial) SO AMERICAN JOURNAL OF CARDIOLOGY LA English DT Article ID RANDOMIZED CONTROLLED-TRIAL; PREDICTIVE INSTRUMENT; INFARCTION; INFUSION; MORTALITY; MULTICENTER; THERAPY; ASSIST; HEART AB The Immediate Myocardial Metabolic Enhancement During Initial Assessment and Treatment in Emergency care Trial of very early intravenous glucose-insulin-potassium (GIK) for acute coronary syndromes (ACS) in out-of-hospital emergency medical service (EMS) settings showed 80% reduction in infarct size at 30 days, suggesting potential longer-term benefits. Here we report 1-year outcomes. Prespecified 1-year end points of this randomized, placebo-controlled, double-blind, effectiveness trial included all-cause mortality and composites including cardiac arrest, mortality, or hospitalization for heart failure (HF). Of 871 participants randomized to GIK versus placebo, death occurred within 1 year in 11.6% versus 13.5%, respectively (unadjusted hazard ratio [HR] 0.83, 95% confidence interval [CI] 0.57 to 1.23, p = 0.36). The composite of cardiac arrest or 1-year mortality was 12.8% versus 17.0% (HR 0.71, 95% CI 0.50 to 1.02, p = 0.06). The composite of hospitalization for HF or mortality within 1 year was 17.2% versus 17.2% (FIR 0.98, 95% CI 0.70 to 1.37, p = 0.92). The composite of mortality, cardiac arrest, or HF hospitalization within 1 year was 18.1% versus 20.4% (HR 0.85, 95% CI 0.62 to 1.16, p = 0.30). In patients presenting with suspected ST elevation myocardial infarction, HRs for 1-year mortality and the 3 composites were, respectively, 0.65 (95% CI 0.33 to 1.27, p = 0.21), 0.52 (95% CI 0.30 to 0.92, p = 0.03), 0.63 (95% CI 0.35 to 1.16, p = 0.14), and 0.51 (95% CI 0.30 to 0.87, p = 0.01). In patients with suspected acute coronary syndromes, serious end points generally were lower with GIK than placebo, but the differences were not statistically significant. However, in those with ST elevation myocardial infarction, the composites of cardiac arrest or 1-year mortality, and of cardiac arrest, mortality, or HF hospitalization within 1 year, were significantly reduced. (C) 2014 Elsevier Inc. All rights reserved. C1 [Selker, Harry P. a; Ruthazer, Robin; Beshansky, Joni R.] Tufts Med Ctr, Ctr Cardiovasc Hlth Serv Res, Inst Clin Res & Hlth Policy Studies, Boston, MA 02111 USA. [Udelson, James E.] Tufts Med Ctr, Div Cardiol, Boston, MA USA. [Udelson, James E.] Tufts Med Ctr, Ctr Cardiovasc, Boston, MA USA. [Sheehan, Patricia R.; Vickery, Ellen M.] Tufts Med Ctr, Div Endocrinol Diabet & Metab, Boston, MA USA. [Sheehan, Patricia R.; Vickery, Ellen M.] Tufts Univ, Sch Med, Boston, MA 02111 USA. [Massaro, Joseph M.] Boston Univ, Sch Med, Dept Biostat, Boston, MA 02118 USA. [D'Agostino, Ralph B.] Boston Univ, Dept Math & Stat, Boston, MA 02215 USA. [Griffith, John L.] Northeastern Univ, Bouve Coll Hlth Sci, Boston, MA 02115 USA. [Desvigne-Nickens, Patrice; Rosenberg, Yves; Tian, Xin] NHLBI, NIH, Bethesda, MD 20892 USA. [Atkins, James M.] Univ Texas Southwestern, Sch Med, Dept Med, Dallas, TX USA. [Aufderheide, Tom P.; Pirrallo, Ronald G.] Med Coll Wisconsin, Dept Emergency Med, Milwaukee, WI 53226 USA. [Sayah, Assaad J.] Cambridge Hlth Alliance, Dept Emergency Med, Cambridge, MA USA. [Levy, Michael K.] Alaska Reg Hosp, Dept Emergency Med, Anchorage, AK USA. [Richards, Michael E.; Braude, Darren A.] Univ New Mexico, Sch Med, Hlth Sci Ctr, Dept Med, Albuquerque, NM 87131 USA. [Braude, Darren A.] Univ New Mexico, Sch Med, Hlth Sci Ctr, Dept Anesthesiol, Albuquerque, NM 87131 USA. [Doyle, Delanor D.] Med Ctr Cent Georgia, Dept Emergency Med, Macon, GA USA. [Frascone, Ralph J.] Regions Hosp Emergency Med Serv, St Paul, MN USA. [Kosiak, Donald J.] Avera Med Grp, Sioux Falls, SD USA. [Leaming, James M.] Penn State Hershey Med Ctr, Dept Emergency Med, Hershey, PA USA. [Van Gelder, Carin M.] Johnson Mem Hosp, Dept Emergency Med, Stafford, CT USA. [Van Gelder, Carin M.] Windham Community Mem Hosp, Dept Emergency Med, Willimantic, CT USA. [Walter, Gert-Paul] Emerson Hosp, Dept Emergency Med, Concord, MA USA. [Wayne, Marvin A.] Peace Hlth St Joseph Med Ctr, Dept Emergency Med, Bellingham, WA USA. [Woolard, Robert H.] Texas Tech Univ, Ctr Hlth Sci, Dept Emergency Med, El Paso, TX USA. RP Selker, HP (reprint author), Tufts Med Ctr, Ctr Cardiovasc Hlth Serv Res, Inst Clin Res & Hlth Policy Studies, Boston, MA 02111 USA. EM hselker@tuftsmedicalcenter.org FU National Heart, Lung and Blood Institute (NHLBI) by way of a National Institutes of Health (NIB) Cooperative Agreement [U01HL077821, U01HL077826, U01HL077823]; NIH The National Center for Research Resources [UL1RR025752] FX This study was supported by grants U01HL077821, U01HL077826, and U01HL077823 from the National Heart, Lung and Blood Institute (NHLBI) by way of a National Institutes of Health (NIB) Cooperative Agreement. Role of the Sponsor: Drs. Desvigne-Nickens, Rosenberg, and Tian from NIMBI, respectively, were involved as part of the NIH Cooperative Agreement process in the design and conduct of the study; collection, management, analysis, and interpretation of the data; and preparation, review, and approval of the manuscript. The contents of this article are solely the responsibility of the authors and do not necessarily represent the official views of the NHLBI or the NIH The National Center for Research Resources provided support for specimen processing and testing by way of grant UL1RR025752. Insulin was donated by Eli Lilly and Company, Indianapolis, Indiana. Electrocardiograph-based decision support software was donated by Physio-Control, Redmond, Washington, and Zoll Medical, Chelmsford, Massachusetts. The National Center for Research Resources, Eli Lilly and Company, Physio-Control, and Zoll Medical did not participate in the design and conduct of the study; the collection, management, analysis, and interpretation of the data; and preparation, review, or approval of the manuscript. NR 19 TC 12 Z9 12 U1 0 U2 3 PU EXCERPTA MEDICA INC-ELSEVIER SCIENCE INC PI BRIDGEWATER PA 685 ROUTE 202-206 STE 3, BRIDGEWATER, NJ 08807 USA SN 0002-9149 EI 1879-1913 J9 AM J CARDIOL JI Am. J. Cardiol. PD MAY 15 PY 2014 VL 113 IS 10 BP 1599 EP 1605 DI 10.1016/j.amjcard.2014.02.010 PG 7 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA AH7UA UT WOS:000336339600002 PM 24792735 ER PT J AU Pelser, C Arem, H Pfeiffer, RM Elena, JW Alfano, CM Hollenbeck, AR Park, Y AF Pelser, Colleen Arem, Hannah Pfeiffer, Ruth M. Elena, Joanne W. Alfano, Catherine M. Hollenbeck, Albert R. Park, Yikyung TI Prediagnostic Lifestyle Factors and Survival After Colon and Rectal Cancer Diagnosis in the National Institutes of Health ( NIH)-AARP Diet and Health Study SO CANCER LA English DT Article DE colorectal cancer; survivors; diet; body mass index; smoking; lifestyle ID BODY-MASS INDEX; TREATMENT-RELATED TOXICITY; COLORECTAL-CANCER; PHYSICAL-ACTIVITY; ASSOCIATION; RECURRENCE; OUTCOMES; IMPACT; GUIDELINES; NUTRITION AB BACKGROUNDFew studies have examined the relationship of lifestyle factors with mortality among patients with colorectal cancer. METHODSAmong NIH-AARP Diet and Health study participants, 4213 colon and 1514 rectal cancer cases were identified through linkage to state cancer registries and determined date and cause of death using the National Death Index. Lifestyle factors were assessed at baseline and included: healthy diet (measured by Healthy Eating Index 2005 [HEI-2005]), body mass index (BMI), physical activity, alcohol consumption and smoking. The association of factors was examined individually and combined into a lifestyle score with 5-year mortality from all-causes, colorectal cancer, and cardiovascular disease (CVD). Relative risks (RRs) and 95% confidence intervals (CIs) were estimated using Cox proportional hazards models. RESULTSAmong colon cancer survivors, smokers had increased risk of total mortality (RR=1.74; 95% CI=1.45-2.08) and colorectal cancer mortality (RR=1.46; 95% CI=1.17-1.82), compared to never smokers. Obese (BMI,30) individuals had increased risk of all death (RR=1.19; 95% CI=1.02-1.39) and CVD death (RR=1.84; 95% CI=1.05-3.23), compared to normal weight (BMI, 18.5 to<25) individuals. Compared to those with the lowest lifestyle score, those with the highest score had a 34% lower risk of all-cause mortality (RR=0.66; 95% CI=0.50-0.87). Among rectal cancer survivors, individuals in the highest quintile of HEI-2005 scores had reduced all-cause mortality (RR=0.60; 95% CI=0.42-0.86) compared to those in the lowest. Higher combined lifestyle scores were associated with a 46% lower risk of total mortality (0.54; 0.32-0.91). CONCLUSIONSHealthier lifestyle before cancer diagnosis was associated with improved overall survival after diagnosis with colorectal cancer. Cancer 2014;120:1540-1547 2014. Several modifiable lifestyle factors measured prediagnosis were related to survival among patients with colorectal cancer. A combined lifestyle score consisting of meeting recommendations for diet, body weight, physical activity, alcohol intake, and smoking was also associated with reduced all-cause mortality. C1 [Pelser, Colleen] NCI, Canc Prevent Fellowship Program, Nutr Epidemiol Branch, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. [Pelser, Colleen; Arem, Hannah; Park, Yikyung] NCI, Nutr Epidemiol Branch, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. [Pfeiffer, Ruth M.] NCI, Biostat Branch, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. [Elena, Joanne W.] NCI, Clin & Translat Epidemiol Branch, Div Canc Control & Populat Sci, Bethesda, MD 20892 USA. [Alfano, Catherine M.] NCI, Off Canc Survivorship, Div Canc Control & Populat Sci, Bethesda, MD 20892 USA. [Hollenbeck, Albert R.] AARP, Washington, DC USA. RP Pelser, C (reprint author), Univ Maryland, Greenebaum Canc Ctr, Room N9E02, Baltimore, MD 21201 USA. EM cpelser@umm.edu OI Park, Yikyung/0000-0002-6281-489X FU National Institutes of Health, National Cancer Institute FX Funding provided by the Intramural Research Program of the National Institutes of Health, National Cancer Institute. NR 24 TC 29 Z9 29 U1 0 U2 8 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0008-543X EI 1097-0142 J9 CANCER-AM CANCER SOC JI Cancer PD MAY 15 PY 2014 VL 120 IS 10 BP 1540 EP 1547 DI 10.1002/cncr.28573 PG 8 WC Oncology SC Oncology GA AG4BJ UT WOS:000335363400016 PM 24591061 ER PT J AU Fredriksson, K Mishra, A Lam, JK Mushaben, EM Cuento, RA Meyer, KS Yao, XL Keeran, KJ Nugent, GZ Qu, X Yu, ZX Yang, YQ Raghavachari, N Dagur, PK McCoy, JP Levine, SJ AF Fredriksson, Karin Mishra, Amarjit Lam, Jonathan K. Mushaben, Elizabeth M. Cuento, Rosemarie A. Meyer, Katharine S. Yao, Xianglan Keeran, Karen J. Nugent, Gayle Z. Qu, Xuan Yu, Zu-Xi Yang, Yanqin Raghavachari, Nalini Dagur, Pradeep K. McCoy, J. Philip Levine, Stewart J. TI The Very Low Density Lipoprotein Receptor Attenuates House Dust Mite-Induced Airway Inflammation by Suppressing Dendritic Cell-Mediated Adaptive Immune Responses SO JOURNAL OF IMMUNOLOGY LA English DT Article ID NONINTEGRIN DC-SIGN; C-TYPE LECTIN; VLDL RECEPTOR; PLASMINOGEN-ACTIVATOR; APOLIPOPROTEIN-E; NEURONAL MIGRATION; MICE LACKING; ASTHMA; ALLERGEN; PROTEIN AB The very low density lipoprotein receptor (VLDLR) is a member of the low-density lipoprotein receptor family that binds multiple ligands and plays a key role in brain development. Although the VLDLR mediates pleiotropic biological processes, only a limited amount of information is available regarding its role in adaptive immunity. In this study, we identify an important role for the VLDLR in attenuating house dust mite (HDM)-induced airway inflammation in experimental murine asthma. We show that HDM-challenged Vldlr(-/-) mice have augmented eosinophilic and lymphocytic airway inflammation with increases in Th2 cytokines, C-C chemokines, IgE production, and mucous cell metaplasia. A genome-wide analysis of the lung transcriptome identified that mRNA levels of CD209e (DC-SIGNR4), a murine homolog of DC-SIGN, were increased in the lungs of HDM-challenged Vldlr(-/-) mice, which suggested that the VLDLR might modify dendritic cell (DC) function. Consistent with this, VLDLR expression by human monocyte-derived DCs was increased by HDM stimulation. In addition, 55% of peripheral blood CD11c(+) DCs from individuals with allergy expressed VLDLR under basal conditions. Lastly, the adoptive transfer of HDMpulsed, CD11c(+) bone marrow-derived DCs (BMDCs) from Vldlr(-/)- mice to the airways of wild type recipient mice induced augmented eosinophilic and lymphocytic airway inflammation upon HDM challenge with increases in Th2 cytokines, C-C chemokines, IgE production, and mucous cell metaplasia, as compared with the adoptive transfer of HDM-pulsed, CD11c(+) BMDCs from wild type mice. Collectively, these results identify a novel role for the VLDLR as a negative regulator of DC-mediated adaptive immune responses in HDM-induced allergic airway inflammation. C1 [Fredriksson, Karin; Mishra, Amarjit; Lam, Jonathan K.; Mushaben, Elizabeth M.; Cuento, Rosemarie A.; Meyer, Katharine S.; Yao, Xianglan; Levine, Stewart J.] NHLBI, Lab Asthma & Lung Inflammat, Cardiovasc & Pulm Branch, NIH, Bethesda, MD 20892 USA. [Keeran, Karen J.; Nugent, Gayle Z.] NHLBI, Anim Surg & Resources Core Facil, Div Intramural Res, NIH, Bethesda, MD 20892 USA. [Qu, Xuan; Yu, Zu-Xi] NHLBI, Pathol Core Facil, Div Intramural Res, NIH, Bethesda, MD 20892 USA. [Yang, Yanqin; Raghavachari, Nalini] NHLBI, DNA Sequencing & Genom Core Facil, Div Intramural Res, NIH, Bethesda, MD 20892 USA. [Dagur, Pradeep K.; McCoy, J. Philip] NHLBI, Flow Cytometry Core Facil, Div Intramural Res, NIH, Bethesda, MD 20892 USA. RP Levine, SJ (reprint author), NHLBI, Cardiovasc & Pulm Branch, NIH, Bldg 10,Room 6D03,MSC 1590, Bethesda, MD 20892 USA. EM levines@nhlbi.nih.gov RI MISHRA, AMARJIT/D-7504-2016 OI MISHRA, AMARJIT/0000-0002-3777-0338 FU Division of Intramural Research, National Heart, Lung, and Blood Institute FX This work was supported by the Division of Intramural Research, National Heart, Lung, and Blood Institute. NR 57 TC 4 Z9 4 U1 0 U2 3 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 MAY 15 PY 2014 VL 192 IS 10 BP 4497 EP 4509 DI 10.4049/jimmunol.1301234 PG 13 WC Immunology SC Immunology GA AH2TI UT WOS:000335973600006 PM 24733846 ER PT J AU Olivares-Zavaleta, N Whitmire, WM Kari, L Sturdevant, GL Caldwell, HD AF Olivares-Zavaleta, Norma Whitmire, William M. Kari, Laszlo Sturdevant, Gail L. Caldwell, Harlan D. TI CD8(+) T Cells Define an Unexpected Role in Live-Attenuated Vaccine Protective Immunity against Chlamydia trachomatis Infection in Macaques SO JOURNAL OF IMMUNOLOGY LA English DT Article ID GENITAL-TRACT; TRANSCRIPTIONAL REGULATOR; ORAL IMMUNIZATION; NONHUMAN-PRIMATES; CD4(+); PLASMID; GENES AB Trachoma, caused by the obligate intracellular organism Chlamydia trachomatis, is the world's leading cause of preventable blindness for which a vaccine is needed. We have previously shown that a plasmid-deficient live-attenuated trachoma vaccine delivered ocularly to macaques elicited either solid or partial protective immunity against a virulent ocular challenge. Solidly protected macaques shared the same MHC class II alleles implicating CD4(+) T cells in superior protective immunity. Understandably, we sought to define T cell immune correlates in these animals to potentially improve vaccine efficacy. In this study, following a 2-y resting period, these macaques were boosted i.m. with the live-attenuated trachoma vaccine and their peripheral T cell anamnestic responses studied. Both solidly and partially protected macaques exhibited a CD4(+) and CD8(+) T cell anamnestic response following booster immunization. CD8(+) but not CD4(+) T cells from solidly protected macaques proliferated against soluble chlamydial Ag. We observed a more rapid T cell inflammatory cytokine response in tears of solidly protected animals following ocular rechallenge. Most notably, depletion of CD8(+) T cells in solidly protected macaques completely abrogated protective immunity. Collectively, our findings support the conclusion that CD8(+) T cells play an important but unexpected role in liveattenuated trachoma vaccine-mediated protective immunity. C1 [Olivares-Zavaleta, Norma; Whitmire, William M.; Kari, Laszlo; Sturdevant, Gail L.; Caldwell, Harlan D.] NIAID, Intracellular Parasites Lab, Rocky Mt Labs, NIH, Hamilton, MT 59840 USA. RP Caldwell, HD (reprint author), NIAID, Rocky Mt Labs, 903 South 4th St, Hamilton, MT 59840 USA. EM hcaldwell@niaid.nih.gov FU Intramural Research Program of the National Institute of Allergy and Infectious Diseases, National Institutes of Health FX This work was supported by the Intramural Research Program of the National Institute of Allergy and Infectious Diseases, National Institutes of Health. NR 26 TC 10 Z9 10 U1 0 U2 2 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 MAY 15 PY 2014 VL 192 IS 10 BP 4648 EP 4654 DI 10.4049/jimmunol.1400120 PG 7 WC Immunology SC Immunology GA AH2TI UT WOS:000335973600022 PM 24711617 ER PT J AU Greenlee-Wacker, MC Rigby, KM Kobayashi, SD Porter, AR DeLeo, FR Nauseef, WM AF Greenlee-Wacker, Mallary C. Rigby, Kevin M. Kobayashi, Scott D. Porter, Adeline R. DeLeo, Frank R. Nauseef, William M. TI Phagocytosis of Staphylococcus aureus by Human Neutrophils Prevents Macrophage Efferocytosis and Induces Programmed Necrosis SO JOURNAL OF IMMUNOLOGY LA English DT Article ID FRANCISELLA-TULARENSIS; APOPTOTIC CELLS; RECEPTOR; INFLAMMASOME; NECROPTOSIS; DESTRUCTION; RECRUITMENT; ACTIVATION; INFECTION; SURVIVAL AB Community-associated methicillin-resistant Staphylococcus aureus (CA-MRSA) pose a significant threat to human health. Polymorphonuclear leukocytes (PMN) are the first responders during staphylococcal infection, but 15-50% of the initial ingested inoculum survives within the PMN phagosome and likely contributes directly or indirectly to disease pathogenesis. We hypothesize that surviving intracellular CA-MRSA undermine effective phagocyte-mediated defense by causing a decrease in macrophage uptake of PMN containing viable S. aureus and by promoting PMN lysis. In support of this hypothesis, PMN harboring viable CAMRSA strain USA300 (PMN-SA) upregulated the "don't eat me"signal CD47, remained bound to the surface, and were inefficiently ingested by macrophages. In addition, coculture with PMN-SA altered the macrophage phenotype. Compared to macrophages fed USA300 alone, macrophages challenged with PMN-SA produced more IL-8 and less IL-1 receptor antagonist, TNF-a, activated caspase-1, and IL-1 beta. Although they exhibited some features of apoptosis within 3 h following ingestion of S. aureus, including phosphatidylserine exposure and mitochondrial membrane depolarization, PMN-SA had sustained levels of proliferating cell nuclear Ag expression, absence of caspase activation, and underwent lysis within 6 h following phagocytosis. PMN lysis was dependent on receptor-interacting protein 1, suggesting that PMN-SA underwent programmed necrosis or necroptosis. These data are the first demonstration, to our knowledge, that bacteria can promote sustained expression of proliferating cell nuclear Ag and that human PMN undergo necroptosis. Together, these findings demonstrate that S. aureus surviving within PMN undermine the innate immune response and may provide insight into the pathogenesis of S. aureus disease. C1 [Greenlee-Wacker, Mallary C.; Nauseef, William M.] Univ Iowa, Roy J & Lucille A Carver Coll Med, Inflammat Program, Vet Adm Med Ctr, Iowa City, IA 52240 USA. [Greenlee-Wacker, Mallary C.; Nauseef, William M.] Univ Iowa, Roy J & Lucille A Carver Coll Med, Dept Internal Med, Vet Adm Med Ctr, Iowa City, IA 52240 USA. [Rigby, Kevin M.] Univ Utah, Sch Med, Program Mol Med, Salt Lake City, UT 84112 USA. [Kobayashi, Scott D.; Porter, Adeline R.; DeLeo, Frank R.] NIAID, Lab Human Bacterial Pathogenesis, Rocky Mt Labs, NIH, Hamilton, MT 59840 USA. RP Nauseef, WM (reprint author), Univ Iowa, Roy J & Lucille A Carver Coll Med, Inflammat Program, D160 MTF,2501 Crosspark Rd, Coralville, IA 52241 USA. EM william-nauseef@uiowa.edu OI DeLeo, Frank/0000-0003-3150-2516 FU T32 Training Grant from the University of Iowa [2T32AI007260-26A1]; National Institutes of Health [AI70958, AI044642]; Intramural Research Program of the National Institute of Allergy and Infectious Diseases, National Institutes of Health; merit review award FX This work was supported by T32 Training Grant 2T32AI007260-26A1 from the University of Iowa and the National Institutes of Health (to M.C.G.-W.), National Institutes of Health Grants AI70958 and AI044642 (to W.M.N.), and the Intramural Research Program of the National Institute of Allergy and Infectious Diseases, National Institutes of Health (to F.R.D.). The Nauseef laboratory was supported by a merit review award and use of facilities at the Iowa City Department of Veterans Affairs Medical Center, Iowa City, IA. NR 40 TC 41 Z9 41 U1 1 U2 12 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 MAY 15 PY 2014 VL 192 IS 10 BP 4709 EP 4717 DI 10.4049/jimmunol.1302692 PG 9 WC Immunology SC Immunology GA AH2TI UT WOS:000335973600028 PM 24729616 ER PT J AU Yoo, DG Winn, M Pang, L Moskowitz, SM Malech, HL Leto, TL Rada, B AF Yoo, Dae-goon Winn, Matthew Pang, Lan Moskowitz, Samuel M. Malech, Harry L. Leto, Thomas L. Rada, Balazs TI Release of Cystic Fibrosis Airway Inflammatory Markers from Pseudomonas aeruginosa-Stimulated Human Neutrophils Involves NADPH Oxidase-Dependent Extracellular DNA Trap Formation SO JOURNAL OF IMMUNOLOGY LA English DT Article ID RESPIRATORY EPITHELIUM; PEROXIDASE-ACTIVITY; PULMONARY-FUNCTION; SPUTUM BIOMARKERS; HYPOCHLOROUS ACID; INNATE IMMUNITY; LUNG-FUNCTION; RISK-FACTORS; MYELOPEROXIDASE; INFECTION AB Cystic fibrosis (CF) airways are characterized by bacterial infections, excess mucus production, and robust neutrophil recruitment. The main CF airway pathogen is Pseudomonas aeruginosa. Neutrophils are not capable of clearing the infection. Neutrophil primary granule components, myeloperoxidase (MPO) and human neutrophil elastase (HNE), are inflammatory markers in CF airways, and their increased levels are associated with poor lung function. Identifying the mechanism of MPO and HNE release from neutrophils is of high clinical relevance for CF. In this article, we show that human neutrophils release large amounts of neutrophil extracellular traps (NETs) in the presence of P. aeruginosa. Bacteria are entangled in NETs and colocalize with extracellular DNA. MPO, HNE, and citrullinated histone H4 are all associated with DNA in Pseudomonas-triggered NETs. Both laboratory standard strains and CF isolates of P. aeruginosa induce DNA, MPO, and HNE release from human neutrophils. The increase in peroxidase activity of neutrophil supernatants after Pseudomonas exposure indicates that enzymatically active MPO is released. P. aeruginosa induces a robust respiratory burst in neutrophils that is required for extracellular DNA release. Inhibition of the cytoskeleton prevents Pseudomonas-initiated superoxide production and DNA release. NADPH oxidase inhibition suppresses Pseudomonas-induced release of active MPO and HNE. Blocking MEK/ERK signaling results in only minimal inhibition of DNA release induced by Pseudomonas. Our data describe in vitro details of DNA, MPO, and HNE release from neutrophils activated by P. aeruginosa. We propose that Pseudomonas-induced NET formation is an important mechanism contributing to inflammatory conditions characteristic of CF airways. C1 [Yoo, Dae-goon; Winn, Matthew; Pang, Lan; Rada, Balazs] Univ Georgia, Coll Vet Med, Dept Infect Dis, Athens, GA 30602 USA. [Moskowitz, Samuel M.] Massachusetts Gen Hosp, Dept Pediat, Boston, MA 02114 USA. [Moskowitz, Samuel M.] Harvard Univ, Sch Med, Dept Pediat, Boston, MA 02115 USA. [Malech, Harry L.; Leto, Thomas L.] NIAID, Host Def Lab, NIH, Rockville, MD 20852 USA. RP Rada, B (reprint author), Univ Georgia, Coll Vet Med, Dept Infect Dis, 501 DW Brooks Dr, Athens, GA 30602 USA. EM radab@uga.edu OI Malech, Harry/0000-0001-5874-5775 FU startup funds from the Office of the Vice President for Research, University of Georgia; Intramural Research Program of the National Institutes of Health, National Institute of Allergy and Infectious Diseases FX This work was supported by startup funds from the Office of the Vice President for Research, University of Georgia (to B.R.) and by the Intramural Research Program of the National Institutes of Health, National Institute of Allergy and Infectious Diseases. NR 58 TC 20 Z9 21 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 MAY 15 PY 2014 VL 192 IS 10 BP 4728 EP 4738 DI 10.4049/jimmunol.1301589 PG 11 WC Immunology SC Immunology GA AH2TI UT WOS:000335973600030 PM 24740504 ER PT J AU Imamichi, H Natarajan, V Adelsberger, JW Rehm, CA Lempicki, RA Das, B Hazen, A Imamichi, T Lane, HC AF Imamichi, Hiromi Natarajan, Ven Adelsberger, Joseph W. Rehm, Catherine A. Lempicki, Richard A. Das, Biswajit Hazen, Allison Imamichi, Tomozumi Lane, H. Clifford TI Lifespan of effector memory CD4(+) T cells determined by replication-incompetent integrated HIV-1 provirus SO AIDS LA English DT Article DE genetic marker; integration; replication-incompetent; provirus; in-vivo persistence of CD4-positive T lymphocytes; HIV-1 ID IMMUNODEFICIENCY-VIRUS TYPE-1; IMMUNOLOGICAL MEMORY; VIF PROTEIN; IN-VIVO; HYPERMUTATION; INFECTION; DNA; NAIVE; SEQUENCES; TURNOVER AB Objective: Determining the precise lifespan of human T-cell is challenging due to the inability of standard techniques to distinguish between dividing and dying cells. Here, we measured the lifespan of a pool of T cells that were derived from a single cell 'naturally' labelled with a single integrated clone of a replication-incompetent HIV-1 provirus. Design/methods: Utilizing a combination of techniques, we were able to sequence/map an integration site of a unique provirus with a stop codon at position 42 of the HIV-1 protease. In-vitro reconstruction of this provirus into an infectious clone confirmed its inability to replicate. By combining cell separation and integration site-specific PCR, we were able to follow the fate of this single provirus in multiple T-cell subsets over a 20-year period. As controls, a number of additional integrated proviruses were also sequenced. Results: The replication-incompetent HIV-1 provirus was solely contained in the pool of effector memory CD4(+) T cells for 17 years. The percentage of the total effector memory CD4(+) T cells containing the replication-incompetent provirus peaked at 1% with a functional half-life of 11.1 months. In the process of sequencing multiple proviruses, we also observed high levels of lethal mutations in the peripheral blood pool of proviruses. Conclusion: These data indicate that human effector memory CD4(+) T cells are able to persist in vivo for more than 17 years without detectably reverting to a central memory phenotype. A secondary observation is that the fraction of the pool of integrated HIV-1 proviruses capable of replicating may be considerably less than the 12% currently noted in the literature. C1 [Imamichi, Hiromi; Rehm, Catherine A.; Lane, H. Clifford] NIAID, Clin & Mol Retrovirol Sect, Immunoregulat Lab, NIH, Bethesda, MD 20892 USA. [Natarajan, Ven; Adelsberger, Joseph W.; Lempicki, Richard A.; Das, Biswajit; Hazen, Allison; Imamichi, Tomozumi] Leidos Biomed Res Inc, Clin Serv Program, Appl & Dev Res Directorate, Frederick Natl Lab Canc Res, Frederick, MD USA. RP Lane, HC (reprint author), CRC, 9000 Rockville Pike,Bldg 10,Rm 4-1479,MSC 1460, Bethesda, MD 20892 USA. EM CLANE@niaid.nih.gov RI Lempicki, Richard/E-1844-2012 OI Lempicki, Richard/0000-0002-7059-409X FU National Institute of Allergy and Infectious Diseases of the National Institutes of Health (Bethesda, Maryland); National Cancer Institute, National Institutes of Health [HHSN261200800001E] FX This work was funded through the intramural research programme of the National Institute of Allergy and Infectious Diseases of the National Institutes of Health (Bethesda, Maryland) and in part with federal funds from the National Cancer Institute, National Institutes of Health, under Contract No. HHSN261200800001E. The content of this publication does not necessarily reflect the views or policies of the Department of Health and Human Services, nor does mention of trade names, commercial products or organizations imply endorsement by the U.S. Government. NR 38 TC 13 Z9 13 U1 0 U2 4 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0269-9370 EI 1473-5571 J9 AIDS JI Aids PD MAY 15 PY 2014 VL 28 IS 8 BP 1091 EP 1099 DI 10.1097/QAD.0000000000000223 PG 9 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA AG8FK UT WOS:000335654000002 PM 24492253 ER PT J AU Ellen, JM Kapogiannis, B Fortenberry, JD Xu, JH Willard, N Duval, A Pace, J Loeb, J Monte, D Bethel, J AF Ellen, Jonathan M. Kapogiannis, Bill Fortenberry, J. Dennis Xu, Jiahong Willard, Nancy Duval, Anna Pace, Jill Loeb, Jackie Monte, Dina Bethel, James CA Adolescent Med Trials Network HIV TI HIV viral load levels and CD4(+) cell counts of youth in 14 cities SO AIDS LA English DT Article DE CD4+ cell count; viral load; HIV; linkage to care; youth ID PREVENTION; INFECTION; RISK; TRANSMISSION; CARE; MEN AB Objectives: To describe the HIV viral load and CD4(+) cell counts of youth (12-24 years) in 14 cities from March 2010 through November 2011. Methods: Baseline HIV viral load and CD4(+) cell count data were electronically abstracted in a central location and in an anonymous manner through a random computer-generated coding system without any ability to link codes to individual cases. Results: Among 1409 HIV reported cases, 852 participants had data on both viral load and CD4(+) cell counts. Of these youth, 34% had CD4(+) cell counts of 350 or less, 27% had cell counts from 351 to 500, and 39% had CD4(+) cell counts greater than 500. Youth whose transmission risk was male-to-male sexual contact had higher viral loads compared with youth whose transmission risk was perinatal or heterosexual contact. Greater than 30% of those who reported male-to-male sexual contact had viral loads greater than 50 000 copies, whereas less than 20% of heterosexual contact youth had viral loads greater than 50 000 copies. There were no differences noted in viral load by type of testing site. Conclusion: Most HIV-infected youth have CD4(+) cell counts and viral load levels associated with high rates of sexual transmission. Untreated, these youth may directly contribute to high rates of ongoing transmission. It is essential that any public health test and treat strategy place a strong emphasis on youth, particularly young MSM. C1 [Ellen, Jonathan M.] All Childrens Hosp Johns Hopkins Med, St Petersburg, FL 33701 USA. [Kapogiannis, Bill; Pace, Jill] NICHHD, NIH, Bethesda, MD 20892 USA. [Fortenberry, J. Dennis] Indiana Univ Sch Med, Indianapolis, IN 46202 USA. [Xu, Jiahong; Loeb, Jackie; Monte, Dina; Bethel, James] WESTAT Corp, Rockville, MD 20850 USA. [Willard, Nancy; Duval, Anna] Johns Hopkins Univ, Sch Med, Baltimore, MD USA. RP Ellen, JM (reprint author), All Childrens Hosp Johns Hopkins Med, 501 6th Ave, St Petersburg, FL 33701 USA. EM jellen@jhmi.edu FU Adolescent Medicine Trials Network for HIV/AIDS Interventions (ATN) from the National Institutes of Health through the National Institute of Child Health and Human Development [U01 HD 040533, U01 HD 040474]; National Institute on Drug Abuse; National Institute on Mental Health FX ATN 093 was supported by The Adolescent Medicine Trials Network for HIV/AIDS Interventions (ATN) from the National Institutes of Health (U01 HD 040533 and U01 HD 040474) through the National Institute of Child Health and Human Development (B. Kapogiannis, C. Worrell), with supplemental funding from the National Institutes on Drug Abuse (K. Davenny) and Mental Health (P. Brouwers, S. Allison). NR 18 TC 1 Z9 2 U1 2 U2 6 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0269-9370 EI 1473-5571 J9 AIDS JI Aids PD MAY 15 PY 2014 VL 28 IS 8 BP 1213 EP 1219 DI 10.1097/QAD.0000000000000183 PG 7 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA AG8FK UT WOS:000335654000014 PM 25028912 ER PT J AU Longosz, AF Mehta, SH Kirk, GD Margolick, JB Brown, J Quinn, TC Eshleman, SH Laeyendecker, O AF Longosz, Andrew F. Mehta, Shruti H. Kirk, Gregory D. Margolick, Joseph B. Brown, Joelle Quinn, Thomas C. Eshleman, Susan H. Laeyendecker, Oliver TI Incorrect identification of recent HIV infection in adults in the United States using a limiting-antigen avidity assay SO AIDS LA English DT Article DE incidence; people who inject drugs; misclassification; limiting-antigen avidity; HIV; MSM ID CAPTURE ENZYME-IMMUNOASSAY; ANTIRETROVIRAL TREATMENT; TYPE-1 SEROCONVERSION; SPECIFICITY; COHORT AB Objectives: To evaluate factors associated with misclassification by the limiting-antigen avidity (LAg-avidity) assay among individuals with long-standing HIV infection. Design: Samples were obtained from the Multicenter AIDS Cohort Study and AIDS Linked to the IntraVenous Experience cohort (1089 samples from 667 individuals, 595 samples collected 2-4 years and 494 samples collected 4-8 years after HIV seroconversion). Paired samples from both time points were available for 422 (63.3%) of the 667 individuals. Methods: Samples were considered to be misclassified if the LAg-avidity assay result was 1.5 or less normalized optical density (OD-n) units. Results: Overall, 4.8% (52/1089) of the samples were misclassified, including 1.8% [16/884, 95% confidence interval (CI) 1.09-3.06%] of samples from individuals with viral loads above 400 copies/ml and 1.4% (10/705) of samples from individuals with viral loads above 400 copies/ml and CD4(+) cell counts above 200 cells/mu l (95% CI 0.68-2.60%). Age, race, sex, and mode of HIV acquisition were not associated with misclassification. In an adjusted analysis, viral load below 400 copies/ml [adjusted odds ratio (aOR) 3.72, 95% CI 1.61-8.57], CD4(+) cell count below 50 cells/mu l (aOR 5.41, 95% CI 1.86-15.74), and low LAg-avidity result (<= 1.5 OD-n) from the earlier time point (aOR 5.60, 95% CI 1.55-20.25) were significantly associated with misclassification. Conclusions: The manufacturer of the LAg-avidity assay recommends excluding individuals from incidence surveys who are receiving antiretroviral therapy, are elite suppressors, or have AIDS (CD4(+) cell count <200 cells/mu l). The results of this study indicate that those exclusions do not remove all sources of assay misclassification among individuals with long-standing HIV infection. C1 [Longosz, Andrew F.; Quinn, Thomas C.; Laeyendecker, Oliver] NIAID, Immunoregulat Lab, Div Intramural Res, NIH, Baltimore, MD USA. [Mehta, Shruti H.; Kirk, Gregory D.] Johns Hopkins Bloomberg Sch Publ Hlth, Dept Epidemiol, Baltimore, MD USA. [Margolick, Joseph B.] Johns Hopkins Bloomberg Sch Publ Hlth, Dept Mol Microbiol & Immunol, Baltimore, MD USA. [Brown, Joelle] Univ Calif Los Angeles, Sch Publ Hlth, Dept Epidemiol, Los Angeles, CA 90024 USA. [Quinn, Thomas C.; Laeyendecker, Oliver] Johns Hopkins Univ, Sch Med, Dept Med, Baltimore, MD 21205 USA. [Eshleman, Susan H.] Johns Hopkins Univ, Sch Med, Dept Pathol, Baltimore, MD 21205 USA. RP Laeyendecker, O (reprint author), NIAID, LIR, NIH, 855 North Wolfe St,Room 538A, Baltimore, MD USA. EM olaeyen1@jhmi.edu OI Laeyendecker, Oliver/0000-0002-6429-4760 FU National Institute of Allergy and Infectious Diseases (NIAID), National Institute of Drug Abuse (NIDA); Department of Health and Human Services [UM1-AI068613]; NIH, NIAID [R01-A134826, K22-AI092150-01, R01-A134265]; NICHD [R01-HD 050180]; Division of Intramural Research, NIAID, NIH; National Institute of Mental Health (NIMH), Office of AIDS Research, National Institutes of Health (NIH); [R01-AI095068] FX The HIV Prevention Trials Network (HPTN), funded by the National Institute of Allergy and Infectious Diseases (NIAID), National Institute of Drug Abuse (NIDA) and the National Institute of Mental Health (NIMH), Office of AIDS Research, National Institutes of Health (NIH), Department of Health and Human Services (UM1-AI068613 - Eshleman); and R01-AI095068 (Eshleman/Brookmeyer). Multicenter AIDS Cohort Study (U01 AI35042-21) and the AIDS Linked to the IntraVenous Experience (2R56DA004334-27). The studies that collected samples used for analysis were funded by the NIH, NIAID (R01-A134826, K22-AI092150-01, and R01-A134265), NICHD (R01-HD 050180), and additional support was provided by the Division of Intramural Research, NIAID, NIH. NR 30 TC 12 Z9 12 U1 0 U2 4 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0269-9370 EI 1473-5571 J9 AIDS JI Aids PD MAY 15 PY 2014 VL 28 IS 8 BP 1227 EP 1232 DI 10.1097/QAD.0000000000000221 PG 6 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA AG8FK UT WOS:000335654000016 PM 24513567 ER PT J AU Rowley, CA Ikeda, AK Seidel, M Anaebere, TC Antalek, MD Seamon, C Conrey, AK Mendelsohn, L Nichols, J Gorbach, AM Kato, GJ Ackerman, H AF Rowley, Carol A. Ikeda, Allison K. Seidel, Miles Anaebere, Tiffany C. Antalek, Matthew D. Seamon, Catherine Conrey, Anna K. Mendelsohn, Laurel Nichols, James Gorbach, Alexander M. Kato, Gregory J. Ackerman, Hans TI Microvascular oxygen consumption during sickle cell pain crisis SO BLOOD LA English DT Article ID NEAR-INFRARED SPECTROSCOPY; DISEASE; METABOLISM; MECHANISMS; PULMONARY; INJURY; SEPSIS AB Sickle cell disease is an inherited blood disorder characterized by chronic hemolytic anemia and episodic vaso-occlusive pain crises. Vaso-occlusion occurs when deoxygenated hemoglobin S polymerizes and erythrocytes sickle and adhere in the microvasculature, a process dependent on the concentration of hemoglobin S and the rate of deoxygenation, among other factors. We measured oxygen consumption in the thenar eminence during brachial artery occlusion in sickle cell patients and healthy individuals. Microvascular oxygen consumption was greater in sickle cell patients than in healthy individuals (median [interquartile range]; sickle cell: 0.91 [0.75-1.07] vs healthy: 0.75 [0.62-0.94] -Delta HbO(2)/min, P < .05) and was elevated further during acute pain crisis (crisis: 1.10 [0.78-1.30] vs recovered: 0.88 [0.76-1.03] -Delta HbO(2)/min, P < .05). Increased microvascular oxygen consumption during pain crisis could affect the local oxygen saturation of hemoglobin when oxygen delivery is limiting. Identifying the mechanisms of elevated oxygen consumption during pain crisis might lead to the development of new therapeutic interventions. This trial was registered at www.clinicaltrials.gov as #NCT01568710. C1 [Rowley, Carol A.; Ikeda, Allison K.; Anaebere, Tiffany C.; Ackerman, Hans] NIAID, Lab Malaria & Vector Res, Rockville, MD 20852 USA. [Seidel, Miles; Antalek, Matthew D.; Gorbach, Alexander M.] Natl Inst Biomed Imaging & Bioengn, Infrared Imaging & Thermometry Unit, Bethesda, MD USA. [Seamon, Catherine; Conrey, Anna K.; Mendelsohn, Laurel; Nichols, James; Kato, Gregory J.] NHLBI, Hematol Branch, Bethesda, MD 20892 USA. RP Ackerman, H (reprint author), NIAID, Lab Malaria & Vector Res, 12735 Twinbrook Pkwy,Room 3E-28, Rockville, MD 20852 USA. EM hans.ackerman@nih.gov RI Kato, Gregory/I-7615-2014 OI Kato, Gregory/0000-0003-4465-3217 FU National Institutes of Health at the National Heart, Lung and Blood Institute; National Institute of Allergy and Infectious Diseases; National Institute of Biomedical Imaging and Bioengineering FX This study was supported by the Intramural Research Program of the National Institutes of Health at the National Heart, Lung and Blood Institute, the National Institute of Allergy and Infectious Diseases, and the National Institute of Biomedical Imaging and Bioengineering. NR 21 TC 2 Z9 2 U1 0 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 MAY 15 PY 2014 VL 123 IS 20 BP 3101 EP 3104 DI 10.1182/blood-2013-11-533406 PG 4 WC Hematology SC Hematology GA AH1RU UT WOS:000335899400017 PM 24665133 ER PT J AU Singh, OP Hasker, E Sacks, D Boelaert, M Sundar, S AF Singh, Om Prakash Hasker, Epco Sacks, David Boelaert, Marleen Sundar, Shyam TI Asymptomatic Leishmania Infection: A New Challenge for Leishmania Control SO CLINICAL INFECTIOUS DISEASES LA English DT Editorial Material DE visceral leishmaniasis; asymptomatic infection; immunity ID INDIAN VISCERAL LEISHMANIASIS; KALA-AZAR; DONOVANI INFECTION; RISK-FACTORS; SUBCLINICAL INFECTION; DIRECT AGGLUTINATION; INFANTUM INFECTION; IMMUNE-RESPONSE; EASTERN SUDAN; ENDEMIC AREA AB Visceral leishmaniasis (VL) is a serious parasitic disease, causing high morbidity and mortality in the developing world. The pathogenesis of VL is complex, and the clinical presentation ranges from asymptomatic infection to severe and fatal disease. Despite a wealth of research on the full-blown "clinical VL" syndrome, asymptomatic leishmania infections remain poorly understood. Asymptomatic infection could present a major challenge for control programs if its infectiousness is confirmed. In this viewpoint, we highlight the crucial knowledge gaps as well as the obstacles in research on asymptomatic leishmanial infection. Research in this area is essential for the development of more-effective VL control strategies. C1 [Singh, Om Prakash; Sundar, Shyam] Banaras Hindu Univ, Inst Med Sci, Dept Med, Infect Dis Res Lab, Varanasi 221005, Uttar Pradesh, India. [Hasker, Epco; Boelaert, Marleen] Inst Trop Med, Dept Publ Hlth, B-2000 Antwerp, Belgium. [Sacks, David] NIAID, Parasit Dis Lab, NIH, Bethesda, MD 20892 USA. RP Sundar, S (reprint author), Banaras Hindu Univ, Inst Med Sci, Dept Med, Varanasi 221005, Uttar Pradesh, India. EM drshyamsundar@hotmail.com FU NIAID NIH HHS [P50 AI074321, P50AI074321] NR 62 TC 21 Z9 24 U1 2 U2 15 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 MAY 15 PY 2014 VL 58 IS 10 BP 1424 EP 1429 DI 10.1093/cid/ciu102 PG 6 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA AH3RZ UT WOS:000336044200016 PM 24585564 ER PT J AU Lim, JK Tate, JP Fultz, SL Goulet, JL Conigliaro, J Bryant, KJ Gordon, AJ Gibert, C Rimland, D Goetz, MB Klein, MB Fiellin, DA Justice, AC Lo Re, V AF Lim, Joseph K. Tate, Janet P. Fultz, Shawn L. Goulet, Joseph L. Conigliaro, Joseph Bryant, Kendall J. Gordon, Adam J. Gibert, Cynthia Rimland, David Goetz, Matthew Bidwell Klein, Marina B. Fiellin, David A. Justice, Amy C. Lo Re, Vincent, III TI Relationship Between Alcohol Use Categories and Noninvasive Markers of Advanced Hepatic Fibrosis in HIV-Infected, Chronic Hepatitis C Virus-Infected, and Uninfected Patients SO CLINICAL INFECTIOUS DISEASES LA English DT Article DE alcohol; liver fibrosis; HIV; hepatitis C; FIB-4 ID VETERANS AGING COHORT; PLATELET RATIO INDEX; PREDICTING LIVER FIBROSIS; SUBSTANCE USE DISORDERS; ASPARTATE-AMINOTRANSFERASE; PSYCHIATRIC-DIAGNOSIS; SAMPLING VARIABILITY; CIRRHOSIS; VALIDATION; TESTS AB Background. It is unclear if the risk of liver disease associated with different levels of alcohol consumption is higher for patients infected with human immunodeficiency virus (HIV) or chronic hepatitis C virus (HCV). We evaluated associations between alcohol use categories and advanced hepatic fibrosis, by HIV and chronic HCV status. Methods. We performed a cross-sectional study among participants in the Veterans Aging Cohort Study who reported alcohol consumption at enrollment (701 HIV/HCV-coinfected; 1410 HIV-monoinfected; 296 HCV-monoinfected; 1158 HIV/HCV-uninfected). Alcohol use category was determined by the Alcohol Use Disorders Identification Test-Consumption (AUDIT-C) questionnaire and alcohol-related diagnoses and was classified as nonhazardous drinking, hazardous/binge drinking, or alcohol-related diagnosis. Advanced hepatic fibrosis was defined by FIB-4 index >3.25. Results. Within each HIV/HCV group, the prevalence of advanced hepatic fibrosis increased as alcohol use category increased. For each alcohol use category, advanced hepatic fibrosis was more common among HIV-infected than uninfected (nonhazardous: 6.7% vs 1.4%; hazardous/binge: 9.5% vs 3.0%; alcohol-related diagnosis: 19.0% vs 8.6%; P < .01) and chronic HCV-infected than uninfected (nonhazardous: 13.6% vs 2.5%; hazardous/binge: 18.2% vs 3.1%; alcohol-related diagnosis: 22.1% vs 6.5%; P < .01) participants. Strong associations with advanced hepatic fibrosis (adjusted odds ratio [95% confidence interval]) were observed among HIV/HCV-coinfected patients with nonhazardous drinking (14.2 [5.91-34.0]), hazardous/binge drinking (18.9 [7.98-44.8]), and alcohol-related diagnoses (25.2 [10.6-59.7]) compared with uninfected nonhazardous drinkers. Conclusions. Advanced hepatic fibrosis was present at low levels of alcohol consumption, increased with higher alcohol use categories, and was more prevalent among HIV-infected and chronic HCV-infected patients than uninfected individuals. All alcohol use categories were strongly associated with advanced hepatic fibrosis in HIV/HCV-coinfected patients. C1 [Lim, Joseph K.; Tate, Janet P.; Goulet, Joseph L.; Justice, Amy C.] Vet Affairs VA Connecticut Healthcare Syst, West Haven, CT USA. [Lim, Joseph K.; Tate, Janet P.; Goulet, Joseph L.; Fiellin, David A.; Justice, Amy C.] Yale Univ, Sch Med, New Haven, CT USA. [Fultz, Shawn L.] US FDA, Ctr Tobacco Prod, Washington, DC 20204 USA. Hofstra North Shore LIJ Sch Med, Lake Success, NY USA. [Conigliaro, Joseph] North Shore LIJ Hlth Syst, Lake Success, NY USA. [Bryant, Kendall J.] NIAAA, Bethesda, MD USA. [Gordon, Adam J.] Univ Pittsburgh, Pittsburgh, PA 15260 USA. [Gordon, Adam J.] Pittsburgh VA Med Ctr, Pittsburgh, PA USA. [Gibert, Cynthia] VA Med Ctr, Washington, DC USA. [Gibert, Cynthia] George Washington Univ, Med Ctr, Washington, DC 20037 USA. [Rimland, David] Atlanta VA Med Ctr, Atlanta, GA USA. [Rimland, David] Emory Univ, Sch Med, Atlanta, GA 30322 USA. [Goetz, Matthew Bidwell] VA Greater Los Angeles Healthcare Syst, Los Angeles, CA USA. [Goetz, Matthew Bidwell] Univ Calif Los Angeles, David Geffen Sch Med, Los Angeles, CA 90095 USA. [Klein, Marina B.] McGill Univ, Ctr Hlth, Chron Viral Illness Serv, Montreal, PQ, Canada. [Fiellin, David A.; Justice, Amy C.] Yale Univ, Sch Publ Hlth, Yale Ctr Interdisciplinary Res AIDS, New Haven, CT USA. [Lo Re, Vincent, III] Univ Penn, Philadelphia VA Med Ctr, Philadelphia, PA 19104 USA. [Lo Re, Vincent, III] Univ Penn, Perelman Sch Med, Philadelphia, PA 19104 USA. RP Lo Re, V (reprint author), Univ Penn, Perelman Sch Med, Ctr Clin Epidemiol & Biostat, 836 Blockley Hall,423 Guardian Dr, Philadelphia, PA 19104 USA. EM vincentl@mail.med.upenn.edu RI Lo Re, Vincent/N-7817-2015; OI Goetz, Matthew/0000-0003-4542-992X; Fiellin, David/0000-0002-4006-010X; Goulet, Joseph/0000-0002-0842-804X FU National Institute on Alcohol Abuse and Alcoholism [U01 AA13566, R21 AA015894]; National Institute of Allergy and Infectious Diseases [K01 AI070001] FX This study was supported by the National Institute on Alcohol Abuse and Alcoholism (grant numbers U01 AA13566 to A. C. J. and R21 AA015894 to J. K. L and A. C. J.) and the National Institute of Allergy and Infectious Diseases (grant number K01 AI070001 to V. L. R.). NR 60 TC 15 Z9 15 U1 1 U2 5 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 MAY 15 PY 2014 VL 58 IS 10 BP 1449 EP 1458 DI 10.1093/cid/ciu097 PG 10 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA AH3RZ UT WOS:000336044200020 PM 24569533 ER PT J AU Watanabe, M Moon, KD Vacchio, MS Hathcock, KS Hodes, RJ AF Watanabe, Masashi Moon, Kyung Duk Vacchio, Melanie S. Hathcock, Karen S. Hodes, Richard J. TI Downmodulation of Tumor Suppressor p53 by T Cell Receptor Signaling Is Critical for Antigen-Specific CD4(+) T Cell Responses SO IMMUNITY LA English DT Article ID IN-VIVO ACTIVATION; CANCER-THERAPY; IMMUNE-SYSTEM; IL-2 RECEPTOR; CHAIN GENE; MICE; MEMORY; MDM2; INTERLEUKIN-2; TUMORIGENESIS AB Antigen specificity is critical in immune response and requires integration of antigen-specific signals with antigen-nonspecific signals such as those provided by cytokines. The mechanism integrating these pathways is incompletely understood. We report here that antigen-specific proliferative responses of CD4(+) T cells required downmodulation of tumor suppressor p53. In the absence of T cell receptor (TCR) signal, IL-2 induced sustained increase in p53 protein, which prevented proliferative responses despite strong signaling through the IL-2 receptor. In contrast, TCR signaling resulted in early termination of p53 protein expression by decreasing p53 mRNA as well as strong transcriptional induction of the p53-regulating protein Mdm2. Downmodulation of p53 in response to antigen stimulation was in fact critical for antigenspecific T cell proliferation, and preventing p53 degradation by inhibiting Mdm2 resulted in sustained p53 protein and prevented antigen-specific T cell proliferation. It is thus termination of p53 by TCR signaling that allows proliferative responses, enforcing antigen specificity. C1 [Watanabe, Masashi; Moon, Kyung Duk; Vacchio, Melanie S.; Hathcock, Karen S.; Hodes, Richard J.] NCI, Expt Immunol Branch, NIH, Bethesda, MD 20892 USA. RP Hodes, RJ (reprint author), NCI, Expt Immunol Branch, NIH, Bethesda, MD 20892 USA. EM hodesr@31.nia.nih.gov FU Intramural Research Program of the NIH; Uehara Memorial Foundation FX We thank A. Singer, C. Harris, and M. Perry for critical reading of the manuscript and insightful comments during the course of these studies. This work was supported by the Intramural Research Program of the NIH. M.W. was supported by the Uehara Memorial Foundation. NR 39 TC 22 Z9 22 U1 1 U2 4 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 1074-7613 EI 1097-4180 J9 IMMUNITY JI Immunity PD MAY 15 PY 2014 VL 40 IS 5 BP 681 EP 691 DI 10.1016/j.immuni.2014.04.006 PG 11 WC Immunology SC Immunology GA AH3LW UT WOS:000336026100008 PM 24792911 ER PT J AU Kuniholm, MH Jung, M Everhart, JE Cotler, S Heiss, G McQuillan, G Kim, RS Strickler, HD Thyagarajan, B Youngblood, M Kaplan, RC Ho, GYF AF Kuniholm, Mark H. Jung, Molly Everhart, James E. Cotler, Scott Heiss, Gerardo McQuillan, Geraldine Kim, Ryung S. Strickler, Howard D. Thyagarajan, Bharat Youngblood, Marston Kaplan, Robert C. Ho, Gloria Y. F. TI Prevalence of Hepatitis C Virus Infection in US Hispanic/Latino Adults: Results From the NHANES 2007-2010 and HCHS/SOL Studies SO JOURNAL OF INFECTIOUS DISEASES LA English DT Article DE hepatitis C virus; HCV; Hispanic; Latino; United States; prevalence; antibody; RNA; risk factor ID UNITED-STATES; LATINOS; DESIGN AB Prevalence of hepatitis C virus (HCV) antibody has been reported in Mexican Americans, but its prevalence in other US Hispanic/Latino groups is unknown. We studied 2 populations of US Hispanic/Latino adults; 3210 from the National Health and Nutrition Examination Survey (NHANES) 2007-2010 and 11 964 from the Hispanic Community Health Study/Study of Latinos (HCHS/SOL). Age-standardized prevalence of HCV antibody was similar in NHANES 2007-2010 (1.5%) and HCHS/SOL (2.0%) but differed significantly by Hispanic/Latino background in HCHS/SOL (eg, 11.6% in Puerto Rican men vs 0.4% in South American men). These findings suggest that the HCV epidemic among US Hispanics/Latinos is heterogeneous. C1 [Kuniholm, Mark H.; Jung, Molly; Kim, Ryung S.; Strickler, Howard D.; Kaplan, Robert C.; Ho, Gloria Y. F.] Albert Einstein Coll Med, Dept Epidemiol & Populat Hlth, Bronx, NY 10461 USA. [Everhart, James E.] NIDDK, Epidemiol & Data Syst Program, Div Digest Dis & Nutr, Bethesda, MD 20892 USA. [Cotler, Scott] Loyola Univ, Med Ctr, Dept Med, Div Hepatol, Maywood, IL 60153 USA. [Heiss, Gerardo; Youngblood, Marston] Univ N Carolina, Dept Epidemiol, Chapel Hill, NC USA. [McQuillan, Geraldine] Ctr Dis Control & Prevent, Div Hlth & Nutr Examinat Surveys, Hyattsville, MD USA. [Thyagarajan, Bharat] Univ Minnesota, Dept Lab Med & Pathol, Minneapolis, MN 55455 USA. RP Kuniholm, MH (reprint author), Albert Einstein Coll Med, Dept Epidemiol & Populat Hlth, Belfer Bldg,Rm 1308C,1300 Morris Pk Ave, Bronx, NY 10461 USA. EM mark.kuniholm@einstein.yu.edu FU National Heart, Lung, and Blood Institute (NHLBI) [N01-HC65233]; University of Miami [N01-HC65234]; Albert Einstein College of Medicine [N01-HC65235]; Northwestern University [N01-HC65236]; San Diego State University [N01-HC65237]; National Center for Advancing Translational Sciences (NCATS), through CTSA [UL1RR025750, KL2RR025749] FX The Hispanic Community Health Study/Study of Latinos was carried out as a collaborative study supported by contracts from the National Heart, Lung, and Blood Institute (NHLBI) to the University of North Carolina (N01-HC65233), University of Miami (N01-HC65234), Albert Einstein College of Medicine (N01-HC65235), Northwestern University (N01-HC65236), and San Diego State University (N01-HC65237). The following Institutes/Centers/Offices contribute to the HCHS/SOL through a transfer of funds to the NHLBI: National Institute on Minority Health and Health Disparities, National Institute on Deafness and Other Communication Disorders, National Institute of Dental and Craniofacial Research, National Institute of Diabetes and Digestive and Kidney Diseases, National Institute of Neurological Disorders and Stroke, NIH Institution-Office of Dietary Supplements. M. H. K. is supported in part by the National Center for Advancing Translational Sciences (NCATS), through CTSA grants UL1RR025750 and KL2RR025749. NR 8 TC 14 Z9 14 U1 2 U2 5 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 MAY 15 PY 2014 VL 209 IS 10 BP 1585 EP 1590 DI 10.1093/infdis/jit672 PG 6 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA AH4CJ UT WOS:000336073000012 PM 24423693 ER PT J AU Burbelo, PD Bayat, A Rhodes, CS Hoh, R Martin, JN Fromentin, R Chomont, N Hutter, G Kovacs, JA Deeks, SG AF Burbelo, Peter D. Bayat, Ahmad Rhodes, Craig S. Hoh, Rebecca Martin, Jeffrey N. Fromentin, Remi Chomont, Nicolas Huetter, Gero Kovacs, Joseph A. Deeks, Steven G. TI HIV Antibody Characterization as a Method to Quantify Reservoir Size During Curative Interventions SO JOURNAL OF INFECTIOUS DISEASES LA English DT Article DE antibodies; elite controllers; HIV-1; HIV-1 persistence; serology; viral reservoirs ID INFECTION; THERAPY; QUANTIFICATION; REPLICATION; PERSISTENCE AB Quantitative humoral profiling of recent samples from a human immunodeficiency virus (HIV)-infected adult who was cured following a delta32/delta32 CCR5 stem cell transplant in 2007 revealed no antibodies against p24, matrix, nucleocapsid, integrase, protease, and gp120, but low levels of antibodies against reverse transcriptase, tat, and gp41. Antibody levels to these HIV proteins persisted at high and stable levels in most noncontrollers, elite controllers, and antiretroviral-treated subjects, but a rare subset of controllers had low levels of antibodies against matrix, reverse transcriptase, integrase, and/or protease. Comprehensive HIV antibody profiles may prove useful for monitoring curative interventions. C1 [Burbelo, Peter D.] NIDCR, Clin Dent Res Core, Bethesda, MD 20892 USA. [Bayat, Ahmad] NIH, Dept Perioperat Med, Ctr Clin, Bethesda, MD 20892 USA. [Rhodes, Craig S.] Natl Inst Dent & Craniofacial Res, Lab Dev Biol, San Francisco, CA USA. [Hoh, Rebecca; Martin, Jeffrey N.; Deeks, Steven G.] Univ Calif San Francisco, Dept Med, San Francisco, CA USA. [Martin, Jeffrey N.] Univ Calif San Francisco, Dept Epidemiol & Biostat, San Francisco, CA 94143 USA. [Fromentin, Remi; Chomont, Nicolas] Vaccine & Gene Therapy Inst Florida, Port St Lucie, FL USA. [Huetter, Gero] Heidelberg Univ, Inst Transfus Med & Immunol, Mannheim, Germany. [Kovacs, Joseph A.] NIH, Crit Care Med Dept, NIH Clin Ctr, Bethesda, MD 20892 USA. RP Burbelo, PD (reprint author), NIDCR, Clin Dent Res Core, NIH, 10 Ctr Dr,Bldg 10,Rm 5N102-106, Bethesda, MD 20892 USA. EM burbelop@nidcr.nih.gov FU Division of Intramural Research, National Institute of Dental and Craniofacial Research; National Institutes of Health (NIH) Clinical Center; Foundation for AIDS Research (amFAR), NIH [R24 AI067039]; American Foundation for AIDS Research [108264] FX This work was supported by the Division of Intramural Research, National Institute of Dental and Craniofacial Research, the National Institutes of Health (NIH) Clinical Center. National Institutes of Health (NIH) Clinical Center, the Delaney AIDS Research Enterprise (DARE, U19AI096109), the Foundation for AIDS Research (amFAR), NIH Grant R24 AI067039, the National Institute of Allergy and Infectious Diseases (NIAID; K24 AI069994), the University of California, San Francisco (UCSF)/Gladstone Institute of Virology & Immunology CFAR (P30 AI027763), and the UCSF Clinical and Translational Research Institute Clinical Research Center (UL1 RR024131). R. F. is supported by the American Foundation for AIDS Research (amfAR fellowship 108264). NR 15 TC 10 Z9 10 U1 0 U2 7 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 MAY 15 PY 2014 VL 209 IS 10 BP 1613 EP 1617 DI 10.1093/infdis/jit667 PG 5 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA AH4CJ UT WOS:000336073000015 PM 24286982 ER PT J AU Dahl, V Gisslen, M Hagberg, L Peterson, J Shao, W Spudich, S Price, RW Palmer, S AF Dahl, Viktor Gisslen, Magnus Hagberg, Lars Peterson, Julia Shao, Wei Spudich, Serena Price, Richard W. Palmer, Sarah TI An Example of Genetically Distinct HIV Type 1 Variants in Cerebrospinal Fluid and Plasma During Suppressive Therapy SO JOURNAL OF INFECTIOUS DISEASES LA English DT Article DE HIV; cerebrospinal fluid; CSF; central nervous system; CNS; suppressive; therapy; compartmentalization; hypermutants; reservoir ID TREATMENT INTENSIFICATION; ANTIRETROVIRAL THERAPY; INFECTION AB We sequenced the genome of human immunodeficiency virus type 1 (HIV-1) recovered from 70 cerebrospinal fluid (CSF) specimens and 29 plasma samples and corresponding samples obtained before treatment initiation from 17 subjects receiving suppressive therapy. More CSF sequences than plasma sequences were hypermutants. We determined CSF sequences and plasma sequences in specimens obtained from 2 subjects after treatment initiation. In one subject, we found genetically distinct CSF and plasma sequences, indicating that they came from HIV-1 from 2 different compartments, one potentially the central nervous system, during suppressive therapy. In addition, there was little evidence of viral evolution in the CSF during therapy, suggesting that continuous virus replication is not the major cause of viral persistence in the central nervous system. C1 [Dahl, Viktor; Palmer, Sarah] Karolinska Inst, Dept Microbiol Tumor & Cell Biol, Stockholm, Sweden. [Dahl, Viktor; Palmer, Sarah] Swedish Inst Communicable Dis Control, S-17182 Stockholm, Sweden. [Gisslen, Magnus; Hagberg, Lars] Univ Gothenburg, Dept Infect Dis, Gothenburg, Sweden. [Peterson, Julia; Price, Richard W.] Univ Calif San Francisco, Dept Neurol, San Francisco, CA 94143 USA. [Shao, Wei] Sci Applicat Int Corp Frederick, Adv Biomed Comp Ctr, Frederick Natl Lab Canc Res, Frederick, MD USA. [Spudich, Serena] Yale Univ, Dept Neurol, New Haven, CT USA. [Palmer, Sarah] Westmead Millennium Inst, Ctr Virus Res, Westmead, NSW, Australia. [Palmer, Sarah] Univ Sydney, Sydney, NSW 2006, Australia. RP Dahl, V (reprint author), Swedish Inst Communicable Dis Control, S-17182 Stockholm, Sweden. EM viktor.dahl@smi.se OI Dahl, Viktor/0000-0001-9921-5172 FU Foundation for AIDS Research [108021-49-RFRL]; National Institutes of Health [R21 MH096619, R01 MH081772, UL1 RR024131/TR000004, P30 AI027763]; Swedish Research Council [2007-7092]; Sahlgrenska Academy, University of Gothenburg, Sweden [ALFGBG-11067] FX This work was supported by the Foundation for AIDS Research (grant 108021-49-RFRL); the National Institutes of Health (grants R21 MH096619, R01 MH081772, UL1 RR024131/TR000004, and P30 AI027763); the Swedish Research Council (grant 2007-7092); and Sahlgrenska Academy, University of Gothenburg, Sweden (grant ALFGBG-11067). NR 15 TC 10 Z9 10 U1 0 U2 6 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 MAY 15 PY 2014 VL 209 IS 10 BP 1618 EP 1622 DI 10.1093/infdis/jit805 PG 5 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA AH4CJ UT WOS:000336073000016 PM 24338353 ER PT J AU Afonin, KA Kasprzak, W Bindewald, E Puppala, PS Diehl, AR Hall, KT Kim, TJ Zimmermann, MT Jernigan, RL Jaeger, L Shapiro, BA AF Afonin, Kirill A. Kasprzak, Wojciech Bindewald, Eckart Puppala, Praneet S. Diehl, Alex R. Hall, Kenneth T. Kim, Tae Jin Zimmermann, Michael T. Jernigan, Robert L. Jaeger, Luc Shapiro, Bruce A. TI Computational and experimental characterization of RNA cubic nanoscaffolds SO METHODS LA English DT Article DE RNA nanotechnology; RNA architectonics; Anisotropic network model; RNA nanostructure dynamics; RNA nanostructure characterization; Nanostructure design; Native PAGE; TGGE ID ELASTIC NETWORK MODELS; DNA-PACKAGING MOTOR; IN-SILICO; EMERGING FIELD; NUCLEIC-ACIDS; TECTO-RNA; DELIVERY; NANOPARTICLES; MOTIONS; DESIGN AB The fast-developing field of RNA nanotechnology requires the adoption and development of novel and faster computational approaches to modeling and characterization of RNA-based nano-objects. We report the first application of Elastic Network Modeling (ENM), a structure-based dynamics model, to RNA nanotechnology. With the use of an Anisotropic Network Model (ANM), a type of ENM, we characterize the dynamic behavior of non-compact, multi-stranded RNA-based nanocubes that can be used as nano-scale scaffolds carrying different functionalities. Modeling the nanocubes with our tool NanoTiler and exploring the dynamic characteristics of the models with ANM suggested relatively minor but important structural modifications that enhanced the assembly properties and thermodynamic stabilities. In silico and in vitro, we compared nanocubes having different numbers of base pairs per side, showing with both methods that the 10 bp-long helix design leads to more efficient assembly, as predicted computationally. We also explored the impact of different numbers of single-stranded nucleotide stretches at each of the cube corners and showed that cube flexibility simulations help explain the differences in the experimental assembly yields, as well as the measured nanomolecule sizes and melting temperatures. This original work paves the way for detailed computational analysis of the dynamic behavior of artificially designed multi-stranded RNA nanoparticles. (C) 2013 Elsevier Inc. All rights reserved. C1 [Afonin, Kirill A.; Puppala, Praneet S.; Diehl, Alex R.; Hall, Kenneth T.; Kim, Tae Jin; Shapiro, Bruce A.] NCI, Ctr Canc Res, Nanobiol Program, Frederick, MD 21702 USA. [Kasprzak, Wojciech; Bindewald, Eckart] SAIC Frederick Inc, Frederick Natl Lab Canc Res, Ctr Canc Res, Basic Sci Program,Nanobiol Program, Frederick, MD 21702 USA. [Zimmermann, Michael T.; Jernigan, Robert L.] Iowa State Univ, Dept Biochem Biophys & Mol Biol, Ames, IA 50011 USA. [Jaeger, Luc] Univ Calif Santa Barbara, Dept Chem & Biochem, Biomol Sci & Engn Program, Santa Barbara, CA 93106 USA. RP Jaeger, L (reprint author), Univ Calif Santa Barbara, Dept Chem & Biochem, Biomol Sci & Engn Program, Santa Barbara, CA 93106 USA. EM jaeger@chem.ucsb.edu; shapirbr@mail.nih.gov OI Zimmermann, Michael/0000-0001-7073-0525 FU Intramural Research Program of the NIH, National Cancer Institute, Center for Cancer Research; Federal funds; Frederick National Laboratory for Cancer Research, National Institutes of Health [HHSN261200800001E]; NIH [R01GM-079604] FX The authors thank Faye Walker for technical assistance at early stages of this paper, Dr. Buyong Ma and Dr. Hugo Martinez for helpful discussions on certain aspects of the methods employed in this work. This research was supported [in part] by the Intramural Research Program of the NIH, National Cancer Institute, Center for Cancer Research. This project has been funded in whole or in part with Federal funds from the Frederick National Laboratory for Cancer Research, National Institutes of Health, under contract HHSN261200800001E (to WKK and EB). 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 also supported by NIH grant No. R01GM-079604 (to LJ). NR 68 TC 9 Z9 9 U1 0 U2 28 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1046-2023 EI 1095-9130 J9 METHODS JI Methods PD MAY 15 PY 2014 VL 67 IS 2 BP 256 EP 265 DI 10.1016/j.ymeth.2013.10.013 PG 10 WC Biochemical Research Methods; Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA AG7UI UT WOS:000335623900019 PM 24189588 ER PT J AU Heilig, M Schank, JR AF Heilig, Markus Schank, Jesse R. TI Kappa-Opioid Receptor Antagonism: A Mechanism for Treatment of Relief Drinking? SO BIOLOGICAL PSYCHIATRY LA English DT Editorial Material ID DEPENDENCE; RATS C1 [Heilig, Markus] NIAAA, Lab Clin & Translat Studies, NIH, Bethesda, MD 20892 USA. [Schank, Jesse R.] Univ Georgia, Coll Vet Med, Dept Physiol & Pharmacol, Athens, GA 30602 USA. RP Heilig, M (reprint author), NIAAA, 10 Ctr Dr,10-1E-5334, Bethesda, MD 20892 USA. EM markus.heilig@mail.nih.gov OI Heilig, Markus/0000-0003-2706-2482 NR 10 TC 2 Z9 2 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0006-3223 EI 1873-2402 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD MAY 15 PY 2014 VL 75 IS 10 BP 750 EP 751 DI 10.1016/j.biopsych.2014.03.004 PG 2 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA AG6DF UT WOS:000335508000002 PM 24780009 ER PT J AU Dobbs, LK Cunningham, CL AF Dobbs, Lauren K. Cunningham, Christopher L. TI The role of the laterodorsal tegmental nucleus in methamphetamine conditioned place preference and locomotor activity SO BEHAVIOURAL BRAIN RESEARCH LA English DT Article DE Electrolytic lesion; Methamphetamine; Reward; Locomotor activity; Acetylcholine; Inbred mice (C57BL/6) ID BEHAVIORAL SENSITIZATION; SUBSTANTIA-NIGRA; AREA; AMPHETAMINE; NEURONS; MICE; RAT; PEDUNCULOPONTINE; ACETYLCHOLINE; SCOPOLAMINE AB Methamphetamine (METH) indirectly stimulates the laterodorsal tegmental nucleus (LDT) acetylcholine (ACh) neurons to increase ACh within the ventral tegmental area (VTA). LDT ACh inhibition attenuates METH and saline locomotor activity. The aim of these experiments was to determine whether LDT ACh contributes to METH conditioned place preference (CPP). C57BL/6J mice received a bilateral electrolytic or sham lesion of the LDT. After recovery, mice received alternating pairings of METH (0.5 mg/kg) and saline with distinct tactile floor cues over 8 days. During preference tests, mice were given access to both floor types and time spent on each was recorded. Mice were tested again after exposure to both extinction and reconditioning trials. Brains were then processed for choline acetyltransferase immunohistochemistry to label LDT ACh neurons. Lesioned mice had significantly fewer LOT ACh neurons and showed increased saline and METH locomotor activity during the first conditioning trial compared to sham mice. Locomotor activity (saline and METH) was negatively correlated with the number of LDT ACh neurons. Lesioned and sham mice showed similar METH CPP following conditioning, extinction and reconditioning trials. LDT ACh neurons are not necessary for METH reward as indexed by CPP, but may be important for basal and METH-induced locomotor activity. (C) 2014 Elsevier B.V. All rights reserved. C1 [Dobbs, Lauren K.; Cunningham, Christopher L.] Oregon Hlth & Sci Univ, Dept Behav Neurosci, Portland, OR 97239 USA. RP Dobbs, LK (reprint author), NIAAA, NIH, Sect Neuronal Struct, 5625 Fishers Lane,Room TS-24MSC 9411, Bethesda, MD 20892 USA. EM Lauren.dobbs@nih.gov FU National Institutes of Health [R01AA007702, F31DA027295]; Department of Behavioral Neuroscience and by an award from the Achievement Rewards for College Scientists (ARCS) Foundation FX Research reported in this paper was supported by the National Institutes of Health under award numbers R01AA007702 and F31DA027295, by the Department of Behavioral Neuroscience and by an award from the Achievement Rewards for College Scientists (ARCS) Foundation. The content is solely the responsibility of the authors and-does not necessarily represent the official views of the National Institutes of Health. The authors would like to thank Dr. Andrey Ryabinin for assistance with the ChAT IHC procedure. The authors have no conflict of interest to report. NR 26 TC 4 Z9 4 U1 0 U2 4 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0166-4328 EI 1872-7549 J9 BEHAV BRAIN RES JI Behav. Brain Res. PD MAY 15 PY 2014 VL 265 BP 198 EP 202 DI 10.1016/j.bbr.2014.02.021 PG 5 WC Behavioral Sciences; Neurosciences SC Behavioral Sciences; Neurosciences & Neurology GA AF8TV UT WOS:000334989400024 PM 24569009 ER PT J AU Kim, DW Park, JW Willingham, MC Cheng, SY AF Kim, Dong Wook Park, Jeong Won Willingham, Mark C. Cheng, Sheue-yann TI A histone deacetylase inhibitor improves hypothyroidism caused by a TR1 mutant SO HUMAN MOLECULAR GENETICS LA English DT Article ID THYROID-HORMONE RECEPTOR; LIGAND-BINDING DOMAIN; SUBEROYLANILIDE HYDROXAMIC ACID; IN-VIVO; CLINICAL PHENOTYPE; COREPRESSOR NCOR1; NUCLEAR RECEPTORS; RESISTANCE; MUTATION; MICE AB Mutations of the thyroid hormone receptor gene (THRA) cause hypothyroidism in patients with growth and developmental retardation, and skeletal dysplasia. Genetic evidence indicates that the dominant negative activity of TR1 mutants underlies pathological manifestations. Using a mouse model of hypothyroidism caused by a dominant negative TR1PV mutant and its derived mouse model harboring a mutated nuclear receptor corepressor (NCOR1ID) (Thra1(PV/)Ncor1(ID/ID) mice), we recently showed that aberrant release of TR1 mutants from the NCOR1 repressor complex mediates dominant negative actions of TR1 mutants in vivo. We tested the hypothesis that deacetylation of nucleosomal histones associated with aberrant recruitment of corepressors by TR1 mutants underlies pathological phenotypic expression. We treated Thra1(PV/)and Thra1(PV/)Ncor1(ID/ID) mice with a histone deacetylase (HDAC) inhibitor, suberoylanilide hydroxyamic acid (SAHA). SAHA significantly ameliorated the impaired growth, bone development and adipogenesis of Thra1(PV/) mice. In Thra1(PV/)Ncor1(ID/ID) mice, SAHA improved these abnormalities even further. We focused our molecular analyses on how SAHA improved the impaired adipogenesis leading to the lean phenotype. We found that SAHA reverted the impaired adipogenesis by de-repressing the expression of the two master regulators of adipogenesis, C/ebp and Ppar, as well as other adipogenic genes at both the mRNA and protein levels. Chromatin immunoprecipitation analyses indicated SAHA increased the extent of acetylation of nucleosomal H4K5 and H3 to re-activate adipogenic genes to reverting adipogenesis. Thus, HDAC confers in vivo aberrant actions of TR1 mutants. Importantly, for the first time, the present studies show that HDAC inhibitors are clearly beneficial for hypothyroidism and could be therapeutics for treatment. C1 [Kim, Dong Wook; Park, Jeong Won; Willingham, Mark C.; Cheng, Sheue-yann] NCI, Mol Biol Lab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. RP Cheng, SY (reprint author), NCI, Mol Biol Lab, 37 Convent Dr,Room 5128, Bethesda, MD 20892 USA. EM chengs@mail.nih.gov FU Intramural Research Program at the Center for Cancer Research, National Cancer Institute, National Institutes of Health FX The present research was supported by the Intramural Research Program at the Center for Cancer Research, National Cancer Institute, National Institutes of Health. NR 52 TC 6 Z9 6 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 MAY 15 PY 2014 VL 23 IS 10 BP 2651 EP 2664 DI 10.1093/hmg/ddt660 PG 14 WC Biochemistry & Molecular Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Genetics & Heredity GA AF4PB UT WOS:000334694800012 PM 24381310 ER PT J AU Ma, HY Sun, DX Cao, YF Ai, CZ Qu, YQ Hu, CM Jiang, CT Dong, PP Sun, XY Hong, M Tanaka, N Gonzalez, FJ Ma, XC Fang, ZZ AF Ma, Hai-Ying Sun, Dong-Xue Cao, Yun-Feng Ai, Chun-Zhi Qu, Yan-Qing Hu, Cui-Min Jiang, Changtao Dong, Pei-Pei Sun, Xiao-Yu Hong, Mo Tanaka, Naoki Gonzalez, Frank J. Ma, Xiao-Chi Fang, Zhong-Ze TI Herb-drug interaction prediction based on the high specific inhibition of andrographolide derivatives towards UDP-glucuronosyltransferase (UGT) 2B7 SO TOXICOLOGY AND APPLIED PHARMACOLOGY LA English DT Article DE Andrographolide derivatives; Herb-drug interaction (HDI); UDP-glucuronosyltransferases (UGTs); Adverse effects ID ZIDOVUDINE GLUCURONIDATION; PANICULATA EXTRACT; IN-VITRO; ACID; 4-METHYLUMBELLIFERONE; PHARMACOKINETICS; SELECTIVITY; 1-NAPHTHOL; BINDING; SITES AB Herb-drug interaction strongly limits the clinical application of herbs and drugs, and the inhibition of herbal components towards important drug-metabolizing enzymes (DMEs) has been regarded as one of the most important reasons. The present study aims to investigate the inhibition potential of andrographolide derivatives towards one of the most important phase II DMEs UDP-glucuronosyltransferases (UGTs). Recombinant UGT isoforms (except UGT1A4)-catalyzed 4-methylumbelliferone (4-MU) glucuronidation reaction and UGT1A4catalyzed trifluoperazine ( IFP) glucuronidation were employed to firstly screen the andrographolide derivatives' inhibition potential. High specific inhibition of andrographolide derivatives towards UGT2B7 was observed. The inhibition type and parameters (KO were determined for the compounds exhibiting strong inhibition capability towards UGT2B7, and human liver microsome (HLMs)-catalyzed zidovudine (AZT) glucuronidation probe reaction was used to furtherly confirm the inhibition behavior. In combination of inhibition parameters (KO and in vivo concentration of andrographolide and dehydroandrographolide, the potential in vivo inhibition magnitude was predicted. Additionally, both the in vitro inhibition data and computational modeling results provide important information for the modification of andrographolide derivatives as selective inhibitors of UGT2B7. Taken together, data obtained from the present study indicated the potential herb-drug interaction between Andrographis paniculata and the drugs mainly undergoing UGT2B7-catalyzed metabolic elimination, and the andrographolide derivatives as potential candidates for the selective inhibitors of UGT2B7. (C) 2014 Elsevier Inc. All rights reserved. C1 [Ma, Hai-Ying] China Med Univ, Affiliated Hosp 4, Shenyang 110032, Peoples R China. [Sun, Dong-Xue] Shenyang Pharmaceut Univ, Sch Tradit Chinese Med, Shenyang 110016, Peoples R China. [Cao, Yun-Feng; Ma, Xiao-Chi; Fang, Zhong-Ze] Liaoning Med Univ, Affiliated Hosp 1, Jinzhou 121001, Peoples R China. [Cao, Yun-Feng; Ai, Chun-Zhi; Hu, Cui-Min; Sun, Xiao-Yu; Hong, Mo; Ma, Xiao-Chi; Fang, Zhong-Ze] Chinese Acad Sci, Dalian Inst Chem Phys, Joint Ctr Translat Med, Dalian 116023, Peoples R China. [Qu, Yan-Qing] Yantaishan Hosp, Yantai, Shandong, Peoples R China. [Jiang, Changtao; Tanaka, Naoki; Gonzalez, Frank J.; Fang, Zhong-Ze] NCI, Lab Metab, Ctr Canc Res, Bethesda, MD 20892 USA. [Hu, Cui-Min] Georgetown Univ, Med Ctr, Dept Microbiol & Immunol, Washington, DC 20057 USA. [Dong, Pei-Pei; Ma, Xiao-Chi] Dalian Med Univ, Acad Integrat Med, Dalian 116044, Peoples R China. [Ma, Xiao-Chi] Med Univ, Coll Pharm, Pharmacokinet & Drug Transport Key Lab, Dalian, Peoples R China. RP Ma, HY (reprint author), China Med Univ, Affiliated Hosp 4, 4 Chongshan Eastern Rd, Shenyang 110032, Peoples R China. EM cmu4h-mhy@126.com; maxc1978@163.com; zzfang228@gmail.com FU National Natural Science Foundation of China [81202586, 81073013, 81274047] FX This work was supported by the National Natural Science Foundation of China (no. 81202586, 81073013,81274047). NR 25 TC 38 Z9 40 U1 7 U2 33 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 MAY 15 PY 2014 VL 277 IS 1 BP 86 EP 94 DI 10.1016/j.taap.2014.02.021 PG 9 WC Pharmacology & Pharmacy; Toxicology SC Pharmacology & Pharmacy; Toxicology GA AG0GZ UT WOS:000335095200010 PM 24631340 ER PT J AU Anderson, WF Rosenberg, PS Katki, HA AF Anderson, William F. Rosenberg, Philip S. Katki, Hormuzd A. TI Tracking and Evaluating Molecular Tumor Markers With Cancer Registry Data: HER2 and Breast Cancer SO JNCI-JOURNAL OF THE NATIONAL CANCER INSTITUTE LA English DT Editorial Material ID ESTROGEN-RECEPTOR; UNITED-STATES; ADJUVANT CHEMOTHERAPY; AGE DISTRIBUTION; EXPRESSION; EPIDEMIOLOGY; SURVEILLANCE; TRASTUZUMAB; ONCOGENE; SUBTYPES C1 [Anderson, William F.; Rosenberg, Philip S.; Katki, Hormuzd A.] NCI, Biostat Branch, Div Canc Epidemiol & Genet, NIH, Bethesda, MD 20892 USA. RP Katki, HA (reprint author), NCI, NIH, Room 7E606,9609 Med Ctr Dr, Bethesda, MD 20892 USA. EM katkih@mail.nih.gov RI Katki, Hormuzd/B-4003-2015 NR 30 TC 2 Z9 2 U1 0 U2 1 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0027-8874 EI 1460-2105 J9 JNCI-J NATL CANCER I JI JNCI-J. Natl. Cancer Inst. PD MAY 14 PY 2014 VL 106 IS 5 AR dju093 DI 10.1093/jnci/dju093 PG 3 WC Oncology SC Oncology GA AO8WM UT WOS:000341636100022 ER PT J AU Cao, Y Lindstrom, S Schumacher, F Stevens, VL Albanes, D Berndt, SI Boeing, H Bueno-de-Mesquita, HB Canzian, F Chamosa, S Chanock, SJ Diver, WR Gapstur, SM Gaziano, JM Giovannucci, EL Haiman, CA Henderson, B Johansson, M Le Marchand, L Palli, D Rosner, B Siddiq, A Stampfer, M Stram, DO Tamimi, R Travis, RC Trichopoulos, D Willett, WC Yeager, M Kraft, P Hsing, AW Pollak, M Lin, XH Ma, J AF Cao, Yin Lindstroem, Sara Schumacher, Fredrick Stevens, Victoria L. Albanes, Demetrius Berndt, Sonja I. Boeing, Heiner Bueno-de-Mesquita, H. Bas Canzian, Federico Chamosa, Saioa Chanock, Stephen J. Diver, W. Ryan Gapstur, Susan M. Gaziano, J. Michael Giovannucci, Edward L. Haiman, Christopher A. Henderson, Brian Johansson, Mattias Le Marchand, Loic Palli, Domenico Rosner, Bernard Siddiq, Afshan Stampfer, Meir Stram, Daniel O. Tamimi, Rulla Travis, Ruth C. Trichopoulos, Dimitrios Willett, Walter C. Yeager, Meredith Kraft, Peter Hsing, Ann W. Pollak, Michael Lin, Xihong Ma, Jing TI Insulin-like Growth Factor Pathway Genetic Polymorphisms, Circulating IGF1 and IGFBP3, and Prostate Cancer Survival SO JNCI-JOURNAL OF THE NATIONAL CANCER INSTITUTE LA English DT Article ID GENOME-WIDE ASSOCIATION; FACTOR-I; BINDING PROTEIN-3; OVARIAN-CANCER; RISK; EXPRESSION; RECEPTOR; THERAPY; BREAST; TUMOR AB Background The insulin-like growth factor (IGF) signaling pathway has been implicated in prostate cancer (PCa) initiation, but its role in progression remains unknown. Methods Among 5887 PCa patients (704 PCa deaths) of European ancestry from seven cohorts in the National Cancer Institute Breast and Prostate Cancer Cohort Consortium, we conducted Cox kernel machine pathway analysis to evaluate whether 530 tagging single nucleotide polymorphisms (SNPs) in 26 IGF pathway-related genes were collectively associated with PCa mortality. We also conducted SNP-specific analysis using stratified Cox models adjusting for multiple testing. In 2424 patients (313 PCa deaths), we evaluated the association of prediagnostic circulating IGF1 and IGFBP3 levels and PCa mortality. All statistical tests were two-sided. Results The IGF signaling pathway was associated with PCa mortality (P = .03), and IGF2-AS and SSTR2 were the main contributors (both P = .04). In SNP-specific analysis, 36 SNPs were associated with PCa mortality with P-trend less than .05, but only three SNPs in the IGF2-AS remained statistically significant after gene-based corrections. Two were in linkage disequilibrium (r(2) = 1 for rs1004446 and rs3741211), whereas the third, rs4366464, was independent (r(2) = 0.03). The hazard ratios (HRs) per each additional risk allele were 1.19 (95% confidence interval [CI] = 1.06 to 1.34; P-trend = .003) for rs3741211 and 1.44 (95% CI = 1.20 to 1.73; P-trend < .001) for rs4366464. rs4366464 remained statistically significant after correction for all SNPs (P-trend.corr = .04). Prediagnostic IGF1 (HRhighest (vs lowest quartile) = 0.71; 95% CI = 0.48 to 1.04) and IGFBP3 (HR = 0.93; 95% Cl = 0.65 to 1.34) levels were not associated with PCa mortality. Conclusions The IGF signaling pathway, primarily IGF2-AS and SSTR2 genes, may be important in PCa survival. C1 [Cao, Yin; Lindstroem, Sara; Stampfer, Meir; Tamimi, Rulla; Trichopoulos, Dimitrios; Kraft, Peter; Ma, Jing] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. [Cao, Yin; Giovannucci, Edward L.; Stampfer, Meir; Willett, Walter C.] Harvard Univ, Sch Publ Hlth, Dept Nutr, Boston, MA 02115 USA. [Rosner, Bernard; Lin, Xihong] Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA. [Cao, Yin; Giovannucci, Edward L.; Stampfer, Meir; Tamimi, Rulla; Ma, Jing] Brigham & Womens Hosp, Channing Div Network Med, Boston, MA 02115 USA. [Cao, Yin; Giovannucci, Edward L.; Stampfer, Meir; Tamimi, Rulla; Ma, Jing] Harvard Univ, Sch Med, Boston, MA 02115 USA. [Schumacher, Fredrick; Haiman, Christopher A.; Henderson, Brian; Stram, Daniel O.] Univ So Calif, Keck Sch Med, Dept Prevent Med, Los Angeles, CA 90033 USA. [Stevens, Victoria L.; Diver, W. Ryan; Gapstur, Susan M.] Amer Canc Soc, Epidemiol Res Program, Atlanta, GA 30329 USA. [Albanes, Demetrius; Berndt, Sonja I.; Chanock, Stephen J.; Yeager, Meredith] NCI, Div Canc Epidemiol & Genet, NIH, Bethesda, MD 20892 USA. [Boeing, Heiner] German Inst Human Nutr Potsdam Rehbrucke, Dept Epidemiol, Nuthetal, Germany. [Bueno-de-Mesquita, H. Bas] Natl Inst Publ Hlth & Environm, NL-3720 BA Bilthoven, Netherlands. [Bueno-de-Mesquita, H. Bas] Univ Med Ctr, Dept Gastroenterol & Hepatol, Utrecht, Netherlands. [Canzian, Federico] Deutsch Krebsforschungszentrum, German Canc Res Ctr, Genom Epidemiol Grp C055, Heidelberg, Germany. [Chamosa, Saioa] Basque Reg Hlth Dept & Biodonostia, Publ Hlth Div Gipuzkoa, Epidemiol Unit, Gipuzkoa, Spain. [Chanock, Stephen J.; Yeager, Meredith] Frederick Natl Lab Canc Res, Core Genotyping Facil, Gaithersburg, MD USA. [Gaziano, J. Michael] Brigham & Womens Hosp, Dept Med, Div Prevent Med, Boston, MA 02115 USA. [Gaziano, J. Michael] Brigham & Womens Hosp, Dept Med, Div Aging, Boston, MA 02115 USA. [Gaziano, J. Michael] Boston Vet Affairs Healthcare Syst, Massachusetts Vet Epidemiol & Res Informat Ctr, Boston, MA USA. [Gaziano, J. Michael] Boston Vet Affairs Healthcare Syst, Geriatr Res Educ & Clin Ctr, Boston, MA USA. [Johansson, Mattias] Int Agcy Res Canc, F-69372 Lyon, France. [Johansson, Mattias] Umea Univ, Dept Biobank Res, S-90187 Umea, Sweden. [Le Marchand, Loic] Univ Hawaii, Ctr Canc, Honolulu, HI 96822 USA. [Palli, Domenico] Canc Res & Prevent Inst ISPO, Mol & Nutr Epidemiol Unit, Florence, Italy. [Siddiq, Afshan] Univ London Imperial Coll Sci Technol & Med, Sch Publ Hlth, London, England. [Travis, Ruth C.] Univ Oxford, Canc Epidemiol Unit, Oxford, England. [Trichopoulos, Dimitrios] Acad Athens, Bur Epidemiol Res, Athens, Greece. [Trichopoulos, Dimitrios] Hellen Hlth Fdn, Athens, Greece. [Hsing, Ann W.] Stanford Canc Inst, Canc Prevent Inst Calif, Stanford, CA USA. [Pollak, Michael] McGill Univ, Dept Med, Montreal, PQ, Canada. [Pollak, Michael] McGill Univ, Dept Oncol, Montreal, PQ, Canada. RP Ma, J (reprint author), Brigham & Womens Hosp, Dept Med, Channing Div Network Med, 181 Longwood Ave,Boston, Boston, MA 02115 USA. EM yic576@mail.harvard.edu; jing.ma@channing.harvard.edu OI Chamosa, Saioa/0000-0002-8321-4404; PALLI, Domenico/0000-0002-5558-2437 FU National Cancer Institute [U01-CA98233-07, U54CA155626, U01-CA98710-06, U01-CA98216-06, U01-CA98758-07, CA141298]; National Cancer Institute of Canada [019894]; Hellenic Health Foundation; Associazione Italiana per la Ricerca sul Cancro-AIRC-Milan FX This work was supported by the National Cancer Institute (U01-CA98233-07, U54CA155626, U01-CA98710-06, U01-CA98216-06, U01-CA98758-07, CA141298), National Cancer Institute of Canada (019894), Hellenic Health Foundation, and Associazione Italiana per la Ricerca sul Cancro-AIRC-Milan. NR 35 TC 0 Z9 0 U1 0 U2 5 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0027-8874 EI 1460-2105 J9 JNCI-J NATL CANCER I JI JNCI-J. Natl. Cancer Inst. PD MAY 14 PY 2014 VL 106 IS 5 AR dju218 DI 10.1093/jnci/dju218 PG 10 WC Oncology SC Oncology GA AO8WM UT WOS:000341636100033 ER PT J AU Howlader, N Altekruse, SF Li, CI Chen, VW Clarke, CA Ries, LAG Cronin, KA AF Howlader, Nadia Altekruse, Sean F. Li, Christopher I. Chen, Vivien W. Clarke, Christina A. Ries, Lynn A. G. Cronin, Kathleen A. TI US Incidence of Breast Cancer Subtypes Defined by Joint Hormone Receptor and HER2 Status SO JNCI-JOURNAL OF THE NATIONAL CANCER INSTITUTE LA English DT Article ID AFRICAN-AMERICAN WOMEN; POPULATION; ESTROGEN; SURVIVAL; RECOMMENDATIONS; EPIDEMIOLOGY; PREDICTORS; EXPRESSION; MORTALITY; INTERVAL AB Background In 2010, Surveillance, Epidemiology, and End Results (SEER) registries began collecting human epidermal growth factor 2 (HER2) receptor status for breast cancer cases. Methods Breast cancer subtypes defined by joint hormone receptor (HR; estrogen receptor [ER] and progesterone receptor [PR]) and HER2 status were assessed across the 28% of the US population that is covered by SEER registries. Age-specific incidence rates by subtype were calculated for non-Hispanic (NH) white, NH black, NH Asian Pacific Islander (API), and Hispanic women. Joint HR/HER2 status distributions by age, race/ethnicity, county-level poverty, registry, stage, Bloom-Richardson grade, tumor size, and nodal status were evaluated using multivariable adjusted polytomous logistic regression. All statistical tests were two-sided. Results Among case patients with known HR/HER2 status, 36 810 (72.7%) were found to be HR+/HER2(-), 6193 (12.2%) were triple-negative (HR-/HER2(-)), 5240 (10.3%) were HR+/HER2(+), and 2328 (4.6%) were HR-/HER2(+); 6912 (12%) had unknown HR/HER2 status. NH white women had the highest incidence rate of the HR+/HER2(-) subtype, and NH black women had the highest rate of the triple-negative subtype. Compared with women with the HR+/HER2(-) subtype, triple-negative patients were more likely to be NH black and Hispanic; HR+/HER2(+) patients were more likely to be NH API; and HR-/HER2(+) patients were more likely to be NH black, NH API, and Hispanic. Patients with triple-negative, HR+/HER2(+), and HR-/HER2(+) breast cancer were 10% to 30% less likely to be diagnosed at older ages compared with HR+ /HER2(-) patients and 6.4-fold to 20.0-fold more likely to present with high-grade disease. Conclusions In the future, SEER data can be used to monitor clinical outcomes in women diagnosed with different molecular subtypes of breast cancer for a large portion (approximately 28%) of the US population. C1 [Howlader, Nadia; Altekruse, Sean F.; Ries, Lynn A. G.; Cronin, Kathleen A.] NCI, Surveillance Res Program, Div Canc Control & Populat Sci, Bethesda, MD 20892 USA. [Li, Christopher I.] Univ Washington, Dept Epidemiol, Seattle, WA 98195 USA. [Li, Christopher I.] Fred Hutchinson Canc Res Ctr, Div Publ Hlth Sci, Seattle, WA 98104 USA. [Chen, Vivien W.] Louisiana State Univ, Hlth Sci Ctr, Louisiana Tumor Registry & Epidemiol Program, Sch Publ Hlth, New Orleans, LA USA. [Clarke, Christina A.] Canc Prevent Inst Calif, Fremont, CA USA. [Ries, Lynn A. G.] RiesSearch LLC, Rockville, MD USA. RP Howlader, N (reprint author), NCI, Surveillance Res Program, Div Canc Control & Populat Sci, 9609 Med Ctr Dr, Bethesda, MD 20892 USA. EM howladern@mail.nih.gov FU Surveillance Research Program, Division of Cancer Control and Population Sciences, National Cancer Institute, National Institutes of Health; SEER FX Surveillance Research Program, Division of Cancer Control and Population Sciences, National Cancer Institute, National Institutes of Health contracts with SEER registries. NR 33 TC 51 Z9 51 U1 1 U2 9 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0027-8874 EI 1460-2105 J9 JNCI-J NATL CANCER I JI JNCI-J. Natl. Cancer Inst. PD MAY 14 PY 2014 VL 106 IS 5 AR dju055 DI 10.1093/jnci/dju055 PG 8 WC Oncology SC Oncology GA AO8WM UT WOS:000341636100006 ER PT J AU Palena, C Roselli, M Litzinger, MT Ferroni, P Costarelli, L Spila, A Cavaliere, F Huang, B Fernando, RI Hamilton, DH Jochems, C Tsang, KY Cheng, Q Lyerly, HK Schlom, J Guadagni, F AF Palena, Claudia Roselli, Mario Litzinger, Mary T. Ferroni, Patrizia Costarelli, Leopoldo Spila, Antonella Cavaliere, Francesco Huang, Bruce Fernando, Romaine I. Hamilton, Duane H. Jochems, Caroline Tsang, Kwong-Yok Cheng, Qing Lyerly, H. Kim Schlom, Jeffrey Guadagni, Fiorella TI Overexpression of the EMT Driver Brachyury in Breast Carcinomas: Association With Poor Prognosis SO JNCI-JOURNAL OF THE NATIONAL CANCER INSTITUTE LA English DT Article ID EPITHELIAL-MESENCHYMAL TRANSITION; TRANSCRIPTION FACTOR BRACHYURY; BASAL-LIKE PHENOTYPE; CANCER CELL-LINES; RECEPTOR EXPRESSION; GENE; SNAIL; PROGRESSION; SUBTYPES; HORMONE AB Background The epithelial-mesenchymal transition (EMT) has been implicated as an important process in tumor cell invasion, metastasis, and drug resistance. The transcription factor brachyury has recently been described as a driver of EMT of human carcinoma cells. Methods Brachyury mRNA and protein expression was analyzed in human breast carcinomas and benign tissues. The role of brachyury in breast tumor prognosis and drug resistance and the ability of brachyury-specific T cells to lyse human breast carcinoma cells were also evaluated. Kaplan-Meier analyses were used to evaluate the association between brachyury expression and survival. All statistical tests were two-sided. Results The level of brachyury expression in breast cancer cells was positively associated with their ability to invade the extracellular matrix, efficiently form mammospheres in vitro, and resist the cytotoxic effect of docetaxel. A comparison of survival among breast cancer patients treated with tamoxifen in the adjuvant setting who had tumors with high vs low brachyury mRNA expression demonstrated that high expression of brachyury is associated as an independent variable with higher risk of recurrence (hazard ratio [HR] = 7.5; 95% confidence interval [CI] = 2.4 to 23.5; P = 5.14 x 10(-4)) and distant metastasis (HR = 15.2; 95% CI = 3.5 to 66.3; P = 3.01 x 10(-4)). We also demonstrated that brachyury-specific T cells can lyse human breast carcinoma cells. Conclusions The studies reported here provide the rationale for the use of a vaccine targeting brachyury for the therapy of human breast cancer, either as a monotherapy or in combination therapies. C1 [Palena, Claudia; Litzinger, Mary T.; Huang, Bruce; Fernando, Romaine I.; Hamilton, Duane H.; Jochems, Caroline; Tsang, Kwong-Yok; Schlom, Jeffrey] NCI, Lab Tumor Immunol & Biol, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. [Roselli, Mario] Tor Vergata Univ, Dept Internal Med, Med Oncol Unit, Rome, Italy. [Ferroni, Patrizia; Spila, Antonella; Guadagni, Fiorella] IRCCS San Raffaele Pisana, Interinst Multidisciplinary Biobank, Dept Lab Med & Adv Biotechnol, Rome, Italy. [Costarelli, Leopoldo] San Giovanni Addolorata Hosp, Dept Pathol, Rome, Italy. [Cavaliere, Francesco] San Giovanni Addolorata Hosp, Dept Surg, Rome, Italy. [Cheng, Qing; Lyerly, H. Kim] Duke Univ, Sch Med, Dept Surg, Durham, NC USA. RP Schlom, J (reprint author), NCI, Lab Tumor Immunol & Biol, Ctr Canc Res, NIH, 10 Ctr Dr,Rm 8B09, Bethesda, MD 20892 USA. EM js141c@nih.gov RI Cavaliere, Francesco/J-7635-2016; Ferroni, Patrizia/C-2705-2017; OI Cavaliere, Francesco/0000-0001-6501-8648; Ferroni, Patrizia/0000-0002-9877-8712; Roselli, Mario/0000-0002-2431-6689 FU Center for Cancer Research, National Cancer Institute, National Institutes of Health; Italian Ministry of Instruction, University and Research (MERIT) [RBNE08NKH7]; Department of Defense Breast Cancer Research Program-Clinical Translational Research Award [-W81XWH-12-1-0574] FX This research was supported in part by the Intramural Research Program of the Center for Cancer Research, National Cancer Institute, National Institutes of Health; the Italian Ministry of Instruction, University and Research (MERIT, grant code RBNE08NKH7); and Department of Defense Breast Cancer Research Program-Clinical Translational Research Award (Proposal Title, "Developing a HER3 Vaccine to Prevent Resistance to Endocrine Therapy"/Principal Investigator: Dr. Herbert K. Lyerly/Period of Performance: 30 September 2012-29 September 2017/Contract No. -W81XWH-12-1-0574). NR 46 TC 7 Z9 7 U1 2 U2 7 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0027-8874 EI 1460-2105 J9 JNCI-J NATL CANCER I JI JNCI-J. Natl. Cancer Inst. PD MAY 14 PY 2014 VL 106 IS 5 AR dju054 DI 10.1093/jnci/dju054 PG 12 WC Oncology SC Oncology GA AO8WM UT WOS:000341636100005 ER PT J AU Simmonett, AC Pickard, FC Schaefer, HF Brooks, BR AF Simmonett, Andrew C. Pickard, Frank C. Schaefer, Henry F., III Brooks, Bernard R. TI An efficient algorithm for multipole energies and derivatives based on spherical harmonics and extensions to particle mesh Ewald SO JOURNAL OF CHEMICAL PHYSICS LA English DT Article ID SOLID HARMONICS; BIOLOGICAL RECOGNITION; RECURRENCE RELATIONS; ADDITION THEOREMS; COULOMB OPERATOR; AROMATIC RINGS; TENSOR THEORY; LARGE SYSTEMS; 2 POINTS; EXPANSION AB Next-generation molecular force fields deliver accurate descriptions of non-covalent interactions by employing more elaborate functional forms than their predecessors. Much work has been dedicated to improving the description of the electrostatic potential (ESP) generated by these force fields. A common approach to improving the ESP is by augmenting the point charges on each center with higher-order multipole moments. The resulting anisotropy greatly improves the directionality of the non-covalent bonding, with a concomitant increase in computational cost. In this work, we develop an efficient strategy for enumerating multipole interactions, by casting an efficient spherical harmonic based approach within a particle mesh Ewald (PME) framework. Although the derivation involves lengthy algebra, the final expressions are relatively compact, yielding an approach that can efficiently handle both finite and periodic systems without imposing any approximations beyond PME. Forces and torques are readily obtained, making our method well suited to modern molecular dynamics simulations. (C) 2014 AIP Publishing LLC. C1 [Simmonett, Andrew C.; Pickard, Frank C.; Brooks, Bernard R.] NHLBI, Lab Computat Biol, NIH, Bethesda, MD 20892 USA. [Simmonett, Andrew C.; Schaefer, Henry F., III] Univ Georgia, Ctr Computat Quantum Chem, Athens, GA 30602 USA. RP Simmonett, AC (reprint author), NHLBI, Lab Computat Biol, NIH, Bldg 10, Bethesda, MD 20892 USA. EM andrew.simmonett@nih.gov FU National Science Foundation [CHE-1054286]; National Heart, Lung, and Blood Institute FX The work at UGA was supported by the National Science Foundation, under Grant No. CHE-1054286. The work at the National Institutes of Health was supported by the intramural research program of the National Heart, Lung, and Blood Institute. NR 61 TC 18 Z9 18 U1 1 U2 30 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 MAY 14 PY 2014 VL 140 IS 18 AR 184101 DI 10.1063/1.4873920 PG 7 WC Chemistry, Physical; Physics, Atomic, Molecular & Chemical SC Chemistry; Physics GA AI3SR UT WOS:000336782700048 PM 24832247 ER PT J AU Thurber, KR Tycko, R AF Thurber, Kent R. Tycko, Robert TI Perturbation of nuclear spin polarizations in solid state NMR of nitroxide-doped samples by magic-angle spinning without microwaves SO JOURNAL OF CHEMICAL PHYSICS LA English DT Article ID LATTICE-RELAXATION; ROTATING SOLIDS; SPECTROSCOPY; SENSITIVITY; MAS; DIFFUSION; RESONANCE; POLYMERS; C-13 AB We report solid state C-13 and H-1 nuclear magnetic resonance (NMR) experiments with magic-angle spinning (MAS) on frozen solutions containing nitroxide-based paramagnetic dopants that indicate significant perturbations of nuclear spin polarizations without microwave irradiation. At temperatures near 25 K, H-1 and cross-polarized C-13 NMR signals from N-15, C-13-labeled L-alanine in trinitroxide-doped glycerol/water are reduced by factors as large as six compared to signals from samples without nitroxide doping. Without MAS or at temperatures near 100 K, differences between signals with and without nitroxide doping are much smaller. We attribute most of the reduction of NMR signals under MAS near 25 K to nuclear spin depolarization through the cross-effect dynamic nuclear polarization mechanism, in which three-spin flips drive nuclear polarizations toward equilibrium with spin polarization differences between electron pairs. When T-1e is sufficiently long relative to the MAS rotation period, the distribution of electron spin polarization across the nitroxide electron paramagnetic resonance lineshape can be very different from the corresponding distribution in a static sample at thermal equilibrium, leading to the observed effects. We describe three-spin and 3000-spin calculations that qualitatively reproduce the experimental observations. C1 [Thurber, Kent R.; Tycko, Robert] NIDDK, Chem Phys Lab, NIH, Bethesda, MD 20892 USA. RP Thurber, KR (reprint author), NIDDK, Chem Phys Lab, NIH, Bethesda, MD 20892 USA. EM thurberk@niddk.nih.gov FU National Institute of Diabetes and Digestive and Kidney Diseases, a component of the National Institutes of Health FX This work was supported by the Intramural Research Program of the National Institute of Diabetes and Digestive and Kidney Diseases, a component of the National Institutes of Health. We thank Wai-Ming Yau for synthesis of the nitroxide dopants. Numerical calculations used the high-performance computational capabilities of the Biowulf Linux cluster at the National Institutes of Health. NR 37 TC 29 Z9 29 U1 6 U2 51 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 MAY 14 PY 2014 VL 140 IS 18 AR 184201 DI 10.1063/1.4874341 PG 11 WC Chemistry, Physical; Physics, Atomic, Molecular & Chemical SC Chemistry; Physics GA AI3SR UT WOS:000336782700064 PM 24832263 ER PT J AU Funk, E Kottilil, S Gilliam, B Talwani, R AF Funk, Emily Kottilil, Shyam Gilliam, Bruce Talwani, Rohit TI Tickling the TLR7 to cure viral hepatitis SO JOURNAL OF TRANSLATIONAL MEDICINE LA English DT Review DE Hepatitis C; Hepatitis B; Toll-like receptors; TLR7; Hepatitis treatment ID TOLL-LIKE RECEPTORS; ADAPTIVE IMMUNE-RESPONSES; C VIRUS-INFECTION; NONPARENCHYMAL LIVER-CELLS; B E-ANTIGEN; UNITED-STATES; DENDRITIC CELLS; INNATE IMMUNITY; INTERFERON-ALPHA; NATURAL-HISTORY AB Chronic hepatitis B and C are the leading causes of liver disease and liver transplantation worldwide. Ability to mount an effective immune response against both HBV and HCV is associated with spontaneous clearance of both infections, while an inability to do so leads to chronicity of both infections. To mount an effective immune response, both innate and adaptive immune responses must work in tandem. Hence, developing protective immunity to hepatitis viruses is an important goal in order to reduce the global burden of these two infections and prevent development of long-term complications. In this regard, the initial interactions between the pathogen and immune system are pivotal in determining the effectiveness of immune response and subsequent elimination of pathogens. Toll-like receptors (TLRs) are important regulators of innate and adaptive immune responses to various pathogens and are often involved in initiating and augmenting effective antiviral immunity. Immune-based therapeutic strategies that specifically induce type I interferon responses are associated with functional cure for both chronic HBV and HCV infections. Precisely, TLR7 stimulation mediates an endogenous type I interferon response, which is critical in development of a broad, effective and protective immunity against hepatitis viruses. This review focuses on anti-viral strategies that involve targeting TLR7 that may lead to development of protective immunity and eradication of hepatitis B. C1 [Funk, Emily] NIH, Crit Care Med Dept, Clin Res Ctr, Bethesda, MD 20892 USA. [Kottilil, Shyam] NIAID, Lab Immunoregulat, NIH, Bethesda, MD 20892 USA. [Gilliam, Bruce; Talwani, Rohit] Univ Maryland, Sch Med, Inst Human Virol, Baltimore, MD 21201 USA. RP Talwani, R (reprint author), Univ Maryland, Sch Med, Inst Human Virol, 725 West Lombard St N151, Baltimore, MD 21201 USA. EM rtalwani@ihv.umaryland.edu FU Intramural Research Program of the NIH (National Institute of Allergy and Infectious Diseases); Intramural Research Program of the NIH (Clinical Research Center) FX This research was supported by the Intramural Research Program of the NIH (National Institute of Allergy and Infectious Diseases, and the Clinical Research Center). 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 75 TC 7 Z9 8 U1 0 U2 4 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 MAY 14 PY 2014 VL 12 AR 129 DI 10.1186/1479-5876-12-129 PG 8 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA AI5UR UT WOS:000336935200001 PM 24884741 ER PT J AU Craig, VJ Polverino, F Laucho-Contreras, ME Shi, YY Liu, YS Osorio, JC Tesfaigzi, Y Pinto-Plata, V Gochuico, BR Rosas, IO Owen, CA AF Craig, Vanessa J. Polverino, Francesca Laucho-Contreras, Maria E. Shi, Yuanyuan Liu, Yushi Osorio, Juan C. Tesfaigzi, Yohannes Pinto-Plata, Victor Gochuico, Bernadette R. Rosas, Ivan O. Owen, Caroline A. TI Mononuclear Phagocytes and Airway Epithelial Cells: Novel Sources of Matrix Metalloproteinase-8 (MMP-8) in Patients with Idiopathic Pulmonary Fibrosis SO PLOS ONE LA English DT Article ID HUMAN NEUTROPHIL COLLAGENASE; TISSUE INHIBITOR; EXPRESSION; INFLAMMATION; DISEASE; MICE; FIBROBLASTS; SARCOIDOSIS; APOPTOSIS; INJURY AB Objectives: Matrix metalloproteinase-8 (MMP-8) promotes lung fibrotic responses to bleomycin in mice. Although prior studies reported that MMP-8 levels are increased in plasma and bronchoalveolar lavage fluid (BALF) samples from IPF patients, neither the bioactive forms nor the cellular sources of MMP-8 in idiopathic pulmonary fibrosis (IPF) patients have been identified. It is not known whether MMP-8 expression is dys-regulated in IPF leukocytes or whether MMP-8 plasma levels correlate with IPF outcomes. Our goal was to address these knowledge gaps. Methods: We measured MMP-8 levels and forms in blood and lung samples from IPF patients versus controls using ELISAs, western blotting, and qPCR, and assessed whether MMP-8 plasma levels in 73 IPF patients correlate with rate of lung function decline and mortality. We used immunostaining to localize MMP-8 expression in IPF lungs. We quantified MMP-8 levels and forms in blood leukocytes from IPF patients versus controls. Results: IPF patients have increased BALF, whole lung, and plasma levels of soluble MMP-8 protein. Active MMP-8 is the main form elevated in IPF lungs. MMP-8 mRNA levels are increased in monocytes from IPF patients, but IPF patients and controls have similar levels of MMP-8 in PMNs. Surprisingly, macrophages and airway epithelial cells are the main cells expressing MMP-8 in IPF lungs. Plasma and BALF MMP-8 levels do not correlate with decline in lung function and/or mortality in IPF patients. Conclusion: Blood and lung MMP-8 levels are increased in IPF patients. Active MMP-8 is the main form elevated in IPF lungs. Surprisingly, blood monocytes, lung macrophages, and airway epithelial cells are the main cells in which MMP-8 is upregulated in IPF patients. Plasma and BALF MMP-8 levels are unlikely to serve as a prognostic biomarker for IPF patients. These results provide new information about the expression patterns of MMP-8 in IPF patients. C1 [Craig, Vanessa J.; Polverino, Francesca; Laucho-Contreras, Maria E.; Shi, Yuanyuan; Liu, Yushi; Osorio, Juan C.; Pinto-Plata, Victor; Rosas, Ivan O.; Owen, Caroline A.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Div Pulm & Crit Care Med, Boston, MA 02115 USA. [Polverino, Francesca] Univ Parma, Dept Clin & Expt Med, I-43100 Parma, Italy. [Polverino, Francesca; Shi, Yuanyuan; Liu, Yushi; Rosas, Ivan O.; Owen, Caroline A.] Lovelace Resp Res Inst, Pulm Fibrosis Program, Albuquerque, NM USA. [Tesfaigzi, Yohannes; Owen, Caroline A.] Lovelace Resp Res Inst, Chron Obstruct Pulm Dis Program, Albuquerque, NM USA. [Gochuico, Bernadette R.] NHGRI, Med Genet Branch, NIH, Bethesda, MD 20892 USA. RP Owen, CA (reprint author), Harvard Univ, Brigham & Womens Hosp, Sch Med, Div Pulm & Crit Care Med, Boston, MA 02115 USA. EM cowen@rics.bwh.harvard.edu RI Polverino, Francesca/F-3816-2017; OI Polverino, Francesca/0000-0001-9686-5698; Osorio, Juan C/0000-0001-8090-1551 FU Public Health Service, National Heart, Lung, and Blood Institute Grants [HL63137, HL086814, HL111835]; NIH [2T32 HL007633-26, 5T32 HD007466-15]; American Thoracic Society/Pulmonary Fibrosis Foundation; Brigham and Women's Hospital-Lovelace Respiratory Research Institute Consortium; Intramural Research Program of the National Human Genome Research Institute, National Institutes of Health FX This work was supported by the Public Health Service, National Heart, Lung, and Blood Institute Grants HL63137, HL086814, HL111835, NIH 2T32 HL007633-26, NIH 5T32 HD007466-15 (www.grants.gov); the American Thoracic Society/Pulmonary Fibrosis Foundation (www.thoracic.org); and the Brigham and Women's Hospital-Lovelace Respiratory Research Institute Consortium (http://brighamandwomens.org and http://www.lrri.org). This work was supported, in part, by the Intramural Research Program of the National Human Genome Research Institute, National Institutes of Health. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 45 TC 4 Z9 4 U1 1 U2 5 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA SN 1932-6203 J9 PLOS ONE JI PLoS One PD MAY 14 PY 2014 VL 9 IS 5 AR e97485 DI 10.1371/journal.pone.0097485 PG 10 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA AI4TJ UT WOS:000336857400099 PM 24828408 ER PT J AU Ji, Y Abrams, N Zhu, W Salinas, E Yu, ZY Palmer, DC Jailwala, P Franco, Z Roychoudhuri, R Stahlberg, E Gattinoni, L Restifo, NP AF Ji, Yun Abrams, Natalie Zhu, Wei Salinas, Eddie Yu, Zhiya Palmer, Douglas C. Jailwala, Parthav Franco, Zulmarie Roychoudhuri, Rahul Stahlberg, Eric Gattinoni, Luca Restifo, Nicholas P. TI Identification of the Genomic Insertion Site of Pmel-1 TCR alpha and beta Transgenes by Next-Generation Sequencing SO PLOS ONE LA English DT Article ID CD8(+) T-CELLS; SUPERIOR ANTITUMOR IMMUNITY; IN-VIVO; ADOPTIVE IMMUNOTHERAPY; TUMOR-REGRESSION; DENDRITIC CELLS; STEM-CELLS; MEMORY; EFFECTOR; ANTIGEN AB The pmel-1 T cell receptor transgenic mouse has been extensively employed as an ideal model system to study the mechanisms of tumor immunology, CD8(+) T cell differentiation, autoimmunity and adoptive immunotherapy. The 'zygosity' of the transgene affects the transgene expression levels and may compromise optimal breeding scheme design. However, the integration sites for the pmel-1 mouse have remained uncharacterized. This is also true for many other commonly used transgenic mice created before the modern era of rapid and inexpensive next-generation sequencing. Here, we show that whole genome sequencing can be used to determine the exact pmel-1 genomic integration site, even with relatively "shallow" (8X) coverage. The results were used to develop a validated polymerase chain reaction-based genotyping assay. For the first time, we provide a quick and convenient polymerase chain reaction method to determine the dosage of pmel-1 transgene for this freely and publically available mouse resource. We also demonstrate that next-generation sequencing provides a feasible approach for mapping foreign DNA integration sites, even when information of the original vector sequences is only partially known. C1 [Ji, Yun; Zhu, Wei; Gattinoni, Luca] NCI, Expt Transplantat & Immunol Branch, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. [Abrams, Natalie; Salinas, Eddie; Jailwala, Parthav; Stahlberg, Eric] Frederick Natl Lab Canc Res, Adv Biomed Comp Ctr, Frederick, MD USA. [Yu, Zhiya; Palmer, Douglas C.; Franco, Zulmarie; Roychoudhuri, Rahul; Restifo, Nicholas P.] NCI, Surg Branch, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. RP Ji, Y (reprint author), NCI, Expt Transplantat & Immunol Branch, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. EM jiyun@mail.nih.gov; restifo@nih.gov RI Gattinoni, Luca/A-2281-2008; Ji, Yun/B-7245-2009; Palmer, Douglas/B-9454-2008; Abrams, Natalie/F-4845-2011; Roychoudhuri, Rahul/A-7442-2010; OI Gattinoni, Luca/0000-0003-2239-3282; Ji, Yun/0000-0001-6340-7009; Palmer, Douglas/0000-0001-5018-5734; Abrams, Natalie/0000-0001-9698-2819; Roychoudhuri, Rahul/0000-0002-5392-1853; Restifo, Nicholas P./0000-0003-4229-4580 FU National Cancer Institute, Center for Cancer Research of the US National Institutes of Health FX This work was supported by the Intramural Research Program of the National Cancer Institute, Center for Cancer Research of the US National Institutes of Health. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 75 TC 6 Z9 6 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 MAY 14 PY 2014 VL 9 IS 5 AR e96650 DI 10.1371/journal.pone.0096650 PG 8 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA AI4TJ UT WOS:000336857400033 PM 24827921 ER PT J AU Sun, YC Jarrett, CO Bosio, CF Hinnebusch, BJ AF Sun, Yi-Cheng Jarrett, Clayton O. Bosio, Christopher F. Hinnebusch, B. Joseph TI Retracing the Evolutionary Path that Led to Flea-Borne Transmission of Yersinia pestis SO CELL HOST & MICROBE LA English DT Article ID EARLY-PHASE TRANSMISSION; BIOFILM FORMATION; ADAPTIVE RADIATION; CAENORHABDITIS-ELEGANS; DIGUANYLATE CYCLASE; ESCHERICHIA-COLI; MURINE TOXIN; PLAGUE; VECTOR; PSEUDOTUBERCULOSIS AB Yersinia pestis is an arthropod-borne bacterial pathogen that evolved recently from Yersinia pseudotuberculosis, an enteric pathogen transmitted via the fecal-oral route. This radical ecological transition can be attributed to a few discrete genetic changes from a still-extant recent ancestor, thus providing a tractable case study in pathogen evolution and emergence. Here, we determined the genetic and mechanistic basis of the evolutionary adaptation of Y. pestis to flea-borne transmission. Remarkably, only four minor changes in the bacterial progenitor, representing one gene gain and three gene losses, enabled transmission by flea vectors. All three loss-of-function mutations enhanced cyclic-di-GMP-mediatedbacterial biofilm formation in the flea foregut, which greatly increased transmissibility. Our results suggest a step-wise evolutionary model in which Y. pestisemerged as a flea-borne clone, with each genetic change incrementally reinforcing the transmission cycle. The model conforms well to the ecological theory of adaptive radiation. C1 [Sun, Yi-Cheng; Jarrett, Clayton O.; Bosio, Christopher F.; Hinnebusch, B. Joseph] NIAID, Lab Zoonot Pathogens, Rocky Mt Labs, NIH, Hamilton, MT 59840 USA. RP Hinnebusch, BJ (reprint author), NIAID, Lab Zoonot Pathogens, Rocky Mt Labs, NIH, 903 South 4th St, Hamilton, MT 59840 USA. EM jhinnebusch@niaid.nih.gov FU Division of Intramural Research; NIAID; NIH from the Program for Changjiang Scholars and Innovative Research Team in University [IRT13007] FX This work was supported by the Division of Intramural Research, NIAID, NIH and grant IRT13007 from the Program for Changjiang Scholars and Innovative Research Team in University to Y.-C. S. We thank J. Callison for molecular biology assistance; K. Lawrence for help with HPLC, A. Athman for help with preparing figures; and T. Schwan, M. Gottesman, J. Shannon, J. Spinner, and I. Chouikha for review of the manuscript. NR 55 TC 18 Z9 20 U1 9 U2 42 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 1931-3128 EI 1934-6069 J9 CELL HOST MICROBE JI Cell Host Microbe PD MAY 14 PY 2014 VL 15 IS 5 BP 578 EP 586 DI 10.1016/j.chom.2014.04.003 PG 9 WC Microbiology; Parasitology; Virology SC Microbiology; Parasitology; Virology GA AH1XE UT WOS:000335914300010 PM 24832452 ER PT J AU Fauci, AS Marston, HD AF Fauci, Anthony S. Marston, Hilary D. TI The Perpetual Challenge of Antimicrobial Resistance SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Editorial Material C1 [Fauci, Anthony S.; Marston, Hilary D.] NIAID, Bethesda, MD 20892 USA. RP Fauci, AS (reprint author), NIAID, 9000 Rockville Pike, Bethesda, MD 20892 USA. EM afauci@niaid.nih.gov NR 9 TC 34 Z9 35 U1 0 U2 11 PU AMER MEDICAL ASSOC PI CHICAGO PA 330 N WABASH AVE, STE 39300, CHICAGO, IL 60611-5885 USA SN 0098-7484 EI 1538-3598 J9 JAMA-J AM MED ASSOC JI JAMA-J. Am. Med. Assoc. PD MAY 14 PY 2014 VL 311 IS 18 BP 1853 EP 1854 DI 10.1001/jama.2014.2465 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA AH0GT UT WOS:000335798100013 PM 24652442 ER PT J AU Lutambi, AM Chitnis, N Briet, OJT Smith, TA Penny, MA AF Lutambi, Angelina Mageni Chitnis, Nakul Briet, Olivier J. T. Smith, Thomas A. Penny, Melissa A. TI Clustering of Vector Control Interventions Has Important Consequences for Their Effectiveness: A Modelling Study SO PLOS ONE LA English DT Article ID AFRICAN MOSQUITOS DIPTERA; TREATED BED NETS; ANOPHELES-GAMBIAE; MALARIA TRANSMISSION; AEDES-AEGYPTI; CULICIDAE; POPULATION; DISPERSAL; DYNAMICS; FUNESTUS AB Vector control interventions have resulted in considerable reductions in malaria morbidity and mortality. When universal coverage cannot be achieved for financial or logistical reasons, the spatial arrangement of vector control is potentially important for optimizing benefits. This study investigated the effect of spatial clustering of vector control interventions on reducing the population of biting mosquitoes. A discrete-space continuous-time mathematical model of mosquito population dynamics and dispersal was extended to incorporate vector control interventions of insecticide treated bednets (ITNs), Indoor residual Spraying (IRS), and larviciding. Simulations were run at varying levels of coverage and degree of spatial clustering. At medium to high coverage levels of each of the interventions or in combination was more effective to spatially spread these interventions than to cluster them. Suggesting that when financial resources are limited, unclustered distribution of these interventions is more effective. Although it is often stated that locally high coverage is needed to achieve a community effect of ITNs or IRS, our results suggest that if the coverage of ITNs or IRS are insufficient to achieve universal coverage, and there is no targeting of high risk areas, the overall effects on mosquito densities are much greater if they are distributed in an unclustered way, rather than clustered in specific localities. Also, given that interventions are often delivered preferentially to accessible areas, and are therefore clustered, our model results show this may be inefficient. This study provides evidence that the effectiveness of an intervention can be highly dependent on its spatial distribution. Vector control plans should consider the spatial arrangement of any intervention package to ensure effectiveness is maximized. C1 [Lutambi, Angelina Mageni; Chitnis, Nakul; Briet, Olivier J. T.; Smith, Thomas A.; Penny, Melissa A.] Swiss Trop & Publ Hlth Inst, Basel, Switzerland. [Lutambi, Angelina Mageni; Chitnis, Nakul; Briet, Olivier J. T.; Smith, Thomas A.; Penny, Melissa A.] Univ Basel, Basel, Switzerland. [Lutambi, Angelina Mageni] Ifakara Hlth Inst, Dar Es Salaam, Tanzania. [Chitnis, Nakul] NIH, Fogarty Int Ctr, Bethesda, MD 20892 USA. RP Lutambi, AM (reprint author), Swiss Trop & Publ Hlth Inst, Basel, Switzerland. EM angelina-m.lutambi@unibas.ch RI Smith, Thomas/B-5569-2015; Chitnis, Nakul/B-3105-2013; Penny, Melissa/N-6838-2015; Briet, Olivier/K-1917-2015 OI Smith, Thomas/0000-0002-3650-9381; Penny, Melissa/0000-0002-4972-593X; Briet, Olivier/0000-0003-1186-2688 FU Bill and Melinda Gates Foundation provided through Swiss TPH FX Funding support was from the Bill and Melinda Gates Foundation provided through Swiss TPH. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 60 TC 4 Z9 4 U1 3 U2 16 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 MAY 13 PY 2014 VL 9 IS 5 AR e97065 DI 10.1371/journal.pone.0097065 PG 11 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA AH8EY UT WOS:000336369200055 PM 24823656 ER PT J AU Yang, M Eyers, F Xiang, Y Guo, M Young, IG Rosenberg, HF Foster, PS AF Yang, Ming Eyers, Fiona Xiang, Yang Guo, Man Young, Ian G. Rosenberg, Helene F. Foster, Paul S. TI Expression Profiling of Differentiating Eosinophils in Bone Marrow Cultures Predicts Functional Links between MicroRNAs and Their Target mRNAs SO PLOS ONE LA English DT Article ID PERIPHERAL-BLOOD EOSINOPHILS; HEMATOPOIETIC STEM-CELLS; TOLL-LIKE RECEPTORS; RHEUMATOID-ARTHRITIS; CATIONIC PROTEIN; INNATE IMMUNITY; DEFICIENT MICE; MAST-CELLS; EX-VIVO; IN-VIVO AB Background: MicroRNAs (miRNAs) are small non-coding RNAs that regulate complex transcriptional networks underpin immune responses. However, little is known about the specific miRNA networks that control differentiation of specific leukocyte subsets. In this study, we profiled miRNA expression during differentiation of eosinophils from bone marrow (BM) progenitors (bmEos), and correlated expression with potential mRNA targets involved in crucial regulatory functions. Profiling was performed on whole BM cultures to document the dynamic changes in miRNA expression in the BM microenvironment over the differentiation period. miRNA for network analysis were identified in BM cultures enriched in differentiating eosinophils, and chosen for their potential ability to target mRNA of factors that are known to play critical roles in eosinophil differentiation pathways or cell identify. Methodology/Principal Findings: We identified 68 miRNAs with expression patterns that were up-or down-regulated 5-fold or more during bmEos differentiation. By employing TargetScan and MeSH databases, we identified 348 transcripts involved in 30 canonical pathways as potentially regulated by these miRNAs. Furthermore, by applying miRanda and Ingenuity Pathways Analysis (IPA), we identified 13 specific miRNAs that are temporally associated with the expression of IL-5R alpha and CCR3 and 14 miRNAs associated with the transcription factors GATA-1/2, PU.1 and C/EBP epsilon. We have also identified 17 miRNAs that may regulate the expression of TLRs 4 and 13 during eosinophil differentiation, although we could identify no miRNAs targeting the prominent secretory effector, eosinophil major basic protein. Conclusions/Significance: This is the first study to map changes in miRNA expression in whole BM cultures during the differentiation of eosinophils, and to predict functional links between miRNAs and their target mRNAs for the regulation of eosinophilopoiesis. Our findings provide an important resource that will promote the platform for further understanding of the role of these non-coding RNAs in the regulation of eosinophil differentiation and function. C1 [Yang, Ming; Eyers, Fiona; Foster, Paul S.] Univ Newcastle, Fac Hlth, Ctr Asthma & Resp Dis, Sch Biomed Sci & Pharm, Callaghan, NSW, Australia. [Yang, Ming; Eyers, Fiona; Foster, Paul S.] Hunter Med Res Inst, Callaghan, NSW, Australia. [Xiang, Yang; Guo, Man] Cent S Univ, Xiangya Sch Med, Dept Physiol, Changsha, Hunan, Peoples R China. [Young, Ian G.] Australian Natl Univ, John Curtin Sch Med Res, Dept Mol Bioscience, Canberra, ACT 2601, Australia. [Rosenberg, Helene F.] NIAID, Inflammat Immunobiol Sect, Lab Allerg Dis, NIH, Bethesda, MD 20892 USA. RP Yang, M (reprint author), Univ Newcastle, Fac Hlth, Ctr Asthma & Resp Dis, Sch Biomed Sci & Pharm, Callaghan, NSW, Australia. EM Ming.Yang@newcastle.edu.au; Paul.Foster@newcastle.edu.au FU National Health and Medical Research Council of Australia; Australian Research Council; Cooperative Research Centre for Asthma and Airways; National Institute of Allergy and Infectious Diseases Division of Intramural Research FX The authors are supported by the National Health and Medical Research Council of Australia, the Australian Research Council, the Cooperative Research Centre for Asthma and Airways and National Institute of Allergy and Infectious Diseases Division of Intramural Research. The funding bodies had no further role in study design; in the collection, analysis and interpretation of data; in the writing of the report; or in the decision to submit the paper for publication. NR 81 TC 2 Z9 3 U1 0 U2 3 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA SN 1932-6203 J9 PLOS ONE JI PLoS One PD MAY 13 PY 2014 VL 9 IS 5 AR e97537 DI 10.1371/journal.pone.0097537 PG 15 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA AH8EY UT WOS:000336369200128 PM 24824797 ER PT J AU Chung, JY Braunschweig, T Hong, SM Kwon, DS Eo, SH Cho, H Hewitt, SM AF Chung, Joon-Yong Braunschweig, Till Hong, Seung-Mo Kwon, David S. Eo, Soo-Heang Cho, HyungJun Hewitt, Stephen M. TI Assessment of vascular endothelial growth factor in formalin fixed, paraffin embedded colon cancer specimens by means of a well-based reverse phase protein array SO PROTEOME SCIENCE LA English DT Article DE Vascular endothelial growth factor; Formalin-fixed paraffin-embedded; Colon cancer; Immunohistochemistry; Reverse-phase protein array ID COLORECTAL-CANCER; FACTOR EXPRESSION; PROGNOSTIC VALUE; STAGE-II; TISSUE; CARCINOMA; VEGF; PROLIFERATION; ANGIOGENESIS; SURVIVAL AB Background: Vascular endothelial growth factor (VEGF) is a critical pro-angiogenic factor, found in a number of cancers, and a target of therapy. It is typically assessed by immunohistochemistry (IHC) in clinical research. However, IHC is not a quantitative assay and is rarely reproducible. We compared VEGF levels in colon cancer by IHC and a quantitative immunoassay on proteins isolated from formalin fixed, paraffin embedded tissues. Results: VEGF expression was studied by means of a well-based reverse phase protein array (RPPA) and immunohistochemistry in 69 colon cancer cases, and compared with various clinicopathologic factors. Protein lysates derived from formalin fixed, paraffin embedded tissue contained measurable immunoreactive VEGF molecules. The VEGF expression level of well differentiated colon cancer was significantly higher than those with moderately and poorly differentiated carcinomas by immunohistochemistry (P = 0.04) and well-based RPPA (P = 0.04). VEGF quantification by well-based RPPA also demonstrated an association with nodal metastasis status (P = 0.05). In addition, the normalized VEGF value by well-based RPPA correlated (r= 0.283, P = 0.018). Furthermore, subgroup analysis by histologic type revealed that adenocarcinoma cases showed significant correlation (r = 0.315, P = 0.031) between well-based RPPA and IHC. Conclusions: The well-based RPPA method is a high throughput and sensitive approach, is an excellent tool for quantification of marker proteins. Notably, this method may be helpful for more objective evaluation of protein expression in cancer patients. C1 [Chung, Joon-Yong; Kwon, David S.; Hewitt, Stephen M.] NCI, Tissue Array Res Program, Pathol Lab, NIH, Bethesda, MD 20892 USA. [Chung, Joon-Yong; Kwon, David S.; Hewitt, Stephen M.] NCI, Appl Mol Pathol Lab, Pathol Lab, NIH, Bethesda, MD 20892 USA. [Braunschweig, Till] Rhein Westfal TH Aachen, Inst Pathol, D-52074 Aachen, Germany. [Hong, Seung-Mo] Univ Ulsan, Coll Med, Asan Med Ctr, Dept Pathol, Seoul 138736, South Korea. [Eo, Soo-Heang; Cho, HyungJun] Korea Univ, Dept Stat, Seoul 136701, South Korea. RP Hewitt, SM (reprint author), NCI, Tissue Array Res Program, Pathol Lab, NIH, Bethesda, MD 20892 USA. EM genejock@helix.nih.gov OI Hewitt, Stephen/0000-0001-8283-1788; Chung, Joon-Yong/0000-0001-5041-5982 FU Intramural Research Program of the National Institutes of Health; National Cancer Institute; Center for Cancer Research FX We thank Kris Ylaya for technical assistance. This research was supported by the Intramural Research Program of the National Institutes of Health, National Cancer Institute, Center for Cancer Research. NR 33 TC 4 Z9 4 U1 0 U2 3 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1477-5956 J9 PROTEOME SCI JI Proteome Sci. PD MAY 13 PY 2014 VL 12 AR 27 DI 10.1186/1477-5956-12-27 PG 8 WC Biochemical Research Methods SC Biochemistry & Molecular Biology GA AI3NF UT WOS:000336767600001 PM 24883046 ER PT J AU Marshall, PA Adebamowo, CA Adeyemo, AA Ogundiran, TO Strenski, T Zhou, J Rotimi, CN AF Marshall, Patricia A. Adebamowo, Clement A. Adeyemo, Adebowale A. Ogundiran, Temidayo O. Strenski, Teri Zhou, Jie Rotimi, Charles N. TI Voluntary participation and comprehension of informed consent in a genetic epidemiological study of breast cancer in Nigeria SO BMC MEDICAL ETHICS LA English DT Article DE Informed consent; Genetic epidemiological research; Breast cancer; Nigeria ID INTERNATIONAL HEALTH RESEARCH; KENYAN COAST; COLLABORATIVE RESEARCH; COMMUNITY ENGAGEMENT; BIOMEDICAL-RESEARCH; HAPMAP PROJECT; VACCINE TRIAL; EXPERIENCES; RESEARCHERS; GUIDELINES AB Background: Studies on informed consent to medical research conducted in low or middle-income settings have increased, including empirical investigations of consent to genetic research. We investigated voluntary participation and comprehension of informed consent among women involved in a genetic epidemiological study on breast cancer in an urban setting of Nigeria comparing women in the case and control groups. Methods: Surveys were administered in face-to-face interviews with 215 participants following their enrollment in the genetic study (106 patients, 109 controls). Audio-taped in-depth interviews were conducted with a sub-sample of 17 (8%) women who completed the survey. Results: The majority of all participants reported being told that participation in the genetic study was voluntary (97%), that they did not feel pressured to participate in the study (99%), and that they could withdraw from the study (81%). The majority of the breast cancer patients (83%) compared to 58% of women in the control group reported that the study purpose was to learn about the genetic inheritance of breast cancer (OR 3.44; 95% CI = 1.66, 7.14, p value = 0.001). Most participants reported being told about study procedures (95%) and study benefits (98%). Sixty-eight percent of the patients, compared to 47% of the control group reported being told about study risks (p-value < 0.001). Of the 165 married women, 19% reported asking permission from their husbands to enroll in the breast cancer study; no one sought permission from local elders. In-depth interviews highlight the use of persuasion and negotiation between a wife and her husband regarding study participation. Conclusions: The global expansion of genetic and genomic research highlights our need to understand informed consent practices for studies in ethnically diverse cultural environments such as Africa. Quantitative and qualitative empirical investigations of the informed consent process for genetic and genomic research will further our knowledge of complex issues associated with communication of information, comprehension, decisional authority and voluntary participation. In the future, the development and testing of innovative strategies to promote voluntary participation and comprehension of the goals of genomic research will contribute to our understanding of strategies that enhance the consent process. C1 [Marshall, Patricia A.] Case Western Reserve Univ, Sch Med, Dept Bioeth, Cleveland, OH 44106 USA. [Adebamowo, Clement A.] Univ Maryland, Sch Med, Inst Human Virol, Dept Epidemiol & Publ Hlth, Baltimore, MD 21201 USA. [Adebamowo, Clement A.] Univ Maryland, Sch Med, Greenebaum Canc Ctr, Baltimore, MD 21201 USA. [Adeyemo, Adebowale A.; Zhou, Jie; Rotimi, Charles N.] NIH, Ctr Res Genom & Global Hlth, Bethesda, MD 20892 USA. [Ogundiran, Temidayo O.] Univ Coll Hosp, Div Oncol, Dept Surg, Ibadan, Nigeria. [Strenski, Teri] Northwestern Univ, Feinberg Sch Med, Chicago, IL 60611 USA. RP Marshall, PA (reprint author), Case Western Reserve Univ, Sch Med, Dept Bioeth, Room TA 227 10900 Euclid Ave, Cleveland, OH 44106 USA. EM pam20@case.edu OI Adeyemo, Adebowale/0000-0002-3105-3231 FU NIH/National Human Genome Research Institute [2 R01 HG002207-04]; National Center on Minority Health and Health Disparity (NCMHD); National Center for Research Resources (NCRR); Center for Genetic Research Ethics and Law, Case Western Reserve University (NIH/National Human Genome Research Institute) [P50-HG-03390] FX This work was supported by funding from NIH/National Human Genome Research Institute (PI: P. Marshall, 2 R01 HG002207-04), the National Center on Minority Health and Health Disparity (NCMHD), the National Center for Research Resources (NCRR), the Center for Genetic Research Ethics and Law, Case Western Reserve University (PI: P. Marshall, NIH/National Human Genome Research Institute, P50-HG-03390). We thank Richard Cooper and Elaine Prewitt for their support in research design and data analysis. NR 64 TC 9 Z9 9 U1 1 U2 10 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1472-6939 J9 BMC MED ETHICS JI BMC Med. Ethics PD MAY 13 PY 2014 VL 15 AR 38 DI 10.1186/1472-6939-15-38 PG 11 WC Ethics; Medical Ethics; Social Sciences, Biomedical SC Social Sciences - Other Topics; Medical Ethics; Biomedical Social Sciences GA AI1OO UT WOS:000336620800001 PM 24885380 ER PT J AU Boudreau, HE Casterline, BW Burke, DJ Leto, TL AF Boudreau, H. E. Casterline, B. W. Burke, D. J. Leto, T. L. TI Wild-type and mutant p53 differentially regulate NADPH oxidase 4 in TGF-beta-mediated migration of human lung and breast epithelial cells SO BRITISH JOURNAL OF CANCER LA English DT Article DE NADPH oxidase; reactive oxygen species (ROS); cell migration; transforming growth factor-beta (TGF-beta); epithelial-to-mesenchymal transition (EMT); mutant p53 ID SMOOTH-MUSCLE-CELLS; FOCAL ADHESION KINASE; GROWTH-FACTOR-BETA; OXYGEN SPECIES PRODUCTION; NOX4 NAD(P)H OXIDASE; MESENCHYMAL TRANSITION; SIGNAL-TRANSDUCTION; ENDOTHELIAL-CELLS; TRANSFORMING GROWTH-FACTOR-BETA-1; TRANSCRIPTIONAL REPRESSION AB Background: Transforming growth factor-beta (TGF-beta) induces the epithelial-to-mesenchymal transition (EMT) leading to increased cell plasticity at the onset of cancer cell invasion and metastasis. Mechanisms involved in TGF-beta-mediated EMT and cell motility are unclear. Recent studies showed that p53 affects TGF-beta/SMAD3-mediated signalling, cell migration, and tumorigenesis. We previously demonstrated that Nox4, a Nox family NADPH oxidase, is a TGF-beta/SMAD3-inducible source of reactive oxygen species (ROS) affecting cell migration and fibronectin expression, an EMT marker, in normal and metastatic breast epithelial cells. Our present study investigates the involvement of p53 in TGF-beta-regulated Nox4 expression and cell migration. Methods: We investigated the effect of wild-type p53 (WT-p53) and mutant p53 proteins on TGF-beta-regulated Nox4 expression and cell migration. Nox4 mRNA and protein, ROS production, cell migration, and focal adhesion kinase (FAK) activation were examined in three different cell models based on their p53 mutational status. H1299, a p53-null lung epithelial cell line, was used for heterologous expression of WT-p53 or mutant p53. In contrast, functional studies using siRNA-mediated knockdown of endogenous p53 were conducted in MDA-MB-231 metastatic breast epithelial cells that express p53-R280K and MCF-10A normal breast cells that have WT-p53. Results: We found that WT-p53 is a potent suppressor of TGF-beta-induced Nox4, ROS production, and cell migration in p53-null lung epithelial (H1299) cells. In contrast, tumour-associated mutant p53 proteins (R175H or R280K) caused enhanced Nox4 expression and cell migration in both TGF-beta-dependent and TGF-beta-independent pathways. Moreover, knockdown of endogenous mutant p53 (R280K) in TGF-beta-treated MDA-MB-231 metastatic breast epithelial cells resulted in decreased Nox4 protein and reduced phosphorylation of FAK, a key regulator of cell motility. Expression of WT-p53 or dominant-negative Nox4 decreased TGF-beta-mediated FAK phosphorylation, whereas mutant p53 (R280K) increased phospho-FAK. Furthermore, knockdown of WT-p53 in MCF-10A normal breast epithelial cells increased basal Nox4 expression, whereas p53-R280K could override endogenous WT-p53 repression of Nox4. Remarkably, immunofluorescence analysis revealed MCF-10A cells expressing p53-R280K mutant showed an upregulation of Nox4 in both confluent and migrating cells. Conclusions: Collectively, our findings define novel opposing functions for WT-p53 and mutant p53 proteins in regulating Nox4-dependent signalling in TGF-beta-mediated cell motility. C1 [Boudreau, H. E.; Casterline, B. W.; Burke, D. J.; Leto, T. L.] NIAID, Host Def Lab, NIH, Rockville, MD 20852 USA. RP Leto, TL (reprint author), NIAID, Host Def Lab, NIH, 12441 Parklawn Dr, Rockville, MD 20852 USA. EM tleto@nih.gov FU Intramural Research Program of the NIH, National Institute of Allergy and Infectious Diseases [ZO1-AI-000614] FX This work was supported by funds from the Intramural Research Program of the NIH, National Institute of Allergy and Infectious Diseases (ZO1-AI-000614). We would like to thank Drs Lucy A Godley and Sharon H Jackson for their careful review of this manuscript, and Joseph Brzostowski for microscopy training and use of LIG core imaging facility. NR 85 TC 12 Z9 13 U1 0 U2 6 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 MAY 13 PY 2014 VL 110 IS 10 BP 2569 EP 2582 DI 10.1038/bjc.2014.165 PG 14 WC Oncology SC Oncology GA AH6OJ UT WOS:000336250000023 PM 24714748 ER PT J AU Little, MP Schaeffer, ML Reulen, RC Abramson, DH Stovall, M Weathers, R de Vathaire, F Diallo, I Seddon, JM Hawkins, MM Tucker, MA Kleinerman, RA AF Little, M. P. Schaeffer, M. L. Reulen, R. C. Abramson, D. H. Stovall, M. Weathers, R. de Vathaire, F. Diallo, I. Seddon, J. M. Hawkins, M. M. Tucker, M. A. Kleinerman, R. A. TI Breast cancer risk after radiotherapy for heritable and non-heritable retinoblastoma: a US-UK study SO BRITISH JOURNAL OF CANCER LA English DT Article DE breast cancer; radiotherapy; alkylating agents; retinoblastoma; genetic risk ID ATOMIC-BOMB SURVIVORS; LONG-TERM SURVIVORS; BRCA2 MUTATION CARRIERS; CHILDHOOD-CANCER; GENE-MUTATIONS; DIAGNOSTIC RADIATION; VISUAL IMPAIRMENT; POOLED ANALYSIS; 2ND CANCER; FOLLOW-UP AB Background: Retinoblastoma is a rare childhood eye cancer caused by germline or somatic mutations in the RB1 gene. Previous studies observed elevated breast cancer risk among retinoblastoma survivors. However, there has been no research on breast cancer risk in relation to radiation (primarily scatter radiation from the primary treatment) and genetic susceptibility of retinoblastoma survivors. Methods: Two groups of retinoblastoma survivors from the US and UK were selected, and breast cancer risk analysed using a case-control methodology, nesting within the respective cohorts, matching on heritability (that is to say, having bilateral retinoblastoma or being unilateral cases with at least one relative with retinoblastoma), and using exact statistical methods. There were a total of 31 cases and 77 controls. Results: Overall there was no significant variation of breast cancer risk with dose (P > 0.5). However, there was a pronounced and significant (P = 0.047) increase in the risk of breast cancer with increasing radiation dose for non-heritable retinoblastoma patients and a slight and borderline significant (P = 0.072) decrease in risk of breast cancer with increasing radiation dose for heritable retinoblastoma patients, implying significant (P = 0.024) heterogeneity in radiation risk between the heritable and non-heritable retinoblastoma groups; this was unaffected by the blindness status. There was no significant effect of any type of alkylating-agent chemotherapy on breast cancer risk (P > 0.5). Conclusions: There is significant radiation-related risk of breast cancer for non-heritable retinoblastoma survivors but no excess risk for heritable retinoblastoma survivors, and no significant risk overall. However, these results are based on very small numbers of cases; therefore, they must be interpreted with caution. C1 [Little, M. P.; Tucker, M. A.; Kleinerman, R. A.] NCI, Div Canc Epidemiol & Genet, Dept Hlth & Human Serv, NIH, Bethesda, MD 20892 USA. [Schaeffer, M. L.] Univ Calif Los Angeles, Dept Stat, Los Angeles, CA 90095 USA. [Reulen, R. C.; Hawkins, M. M.] Univ Birmingham, Sch Hlth & Populat Sci, Ctr Childhood Canc Survivor Studies, Dept Epidemiol & Publ Hlth, Birmingham B15 2TT, W Midlands, England. [Abramson, D. H.] Mem Sloan Kettering Canc Ctr, Ophthalm Oncol Serv, New York, NY 10021 USA. [Stovall, M.; Weathers, R.] Univ Texas MD Anderson Canc Ctr, Dept Radiat Phys, Houston, TX 77030 USA. [de Vathaire, F.; Diallo, I.] Inst Gustave Roussy, INSERM, Unit 1018, Radiat Epidemiol Grp, F-98000 Villejuif, France. [Seddon, J. M.] Tufts Univ New England Med Ctr, Ophthalm Epidemiol & Genet Serv, Boston, MA 02111 USA. RP Little, MP (reprint author), NCI, Div Canc Epidemiol & Genet, Dept Hlth & Human Serv, NIH, Bethesda, MD 20892 USA. EM mark.little@nih.gov RI Tucker, Margaret/B-4297-2015; de Vathaire, Florent/L-2983-2016; OI Kleinerman, Ruth/0000-0001-7415-2478; Little, Mark/0000-0003-0980-7567 FU Intramural Research Program of the National Institutes of Health, National Cancer Institute (NCI), Division of Cancer Epidemiology and Genetics FX We are grateful for the technical assistance of Jeremy Miller and the detailed and helpful comments of Dr Peter Inskip, Dr Ethel Gilbert, and the two referees. This work was supported by the Intramural Research Program of the National Institutes of Health, the National Cancer Institute (NCI), Division of Cancer Epidemiology and Genetics. NR 53 TC 4 Z9 4 U1 0 U2 1 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 MAY 13 PY 2014 VL 110 IS 10 BP 2623 EP 2632 DI 10.1038/bjc.2014.193 PG 10 WC Oncology SC Oncology GA AH6OJ UT WOS:000336250000028 PM 24755883 ER PT J AU Simpson, EA Sclafani, V Paukner, A Hamel, AF Novak, MA Meyer, JS Suomi, SJ Ferrari, PF AF Simpson, Elizabeth A. Sclafani, Valentina Paukner, Annika Hamel, Amanda F. Novak, Melinda A. Meyer, Jerrold S. Suomi, Stephen J. Ferrari, Pier Francesco TI Inhaled oxytocin increases positive social behaviors in newborn macaques SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE imitation recognition; neonatal imitation; individual differences ID AUTISM SPECTRUM DISORDERS; INTRANASAL OXYTOCIN; PLASMA OXYTOCIN; RHESUS MACAQUES; DOSE-RESPONSE; NEURAL BASIS; AFFILIATION; BRAIN; ATTENTION; MONKEYS AB Early caregiver-infant interactions are critical for infants' socioemotional and cognitive development. Several hormones and neuromodulators, including oxytocin, affect these interactions. Exogenous oxytocin promotes social behaviors in several species, including human and nonhuman primates. Although exogenous oxytocin increases social function in adults-including expression recognition and affiliation-it is unknown whether oxytocin can increase social interactions in infants. We hypothesized that nebulized oxytocin would increase affiliative social behaviors and such effects would be modulated by infants' social skills, measured earlier in development. We also hypothesized that oxytocin's effects on social behaviors may be due to its anxiolytic effects. We tested these hypotheses in a blind study by nebulizing 7- to 14-d-old macaques (n = 28) with oxytocin or saline. Following oxytocin administration, infants' facial gesturing at a human caregiver increased, and infants' salivary oxytocin was positively correlated with the time spent in close proximity to a caregiver. Infants' imitative skill (measured earlier in development: 1-7 d of age) predicted oxytocin-associated increases in affiliative behaviors-lip smacking, visual attention to a caregiver, and time in close proximity to a caregiver-suggesting that infants with higher propensities for positive social interactions are more sensitive to exogenous oxytocin. Oxytocin also decreased salivary cortisol, but not stress-related behaviors (e.g., scratching), suggesting the possibility of some anxiolytic effects. To our knowledge, this study provides the first evidence that oxytocin increases positive social behaviors in newborns. This information is of critical importance for potential interventions aimed at ameliorating inadequate social behaviors in infants with higher likelihood of developing neurodevelopmental disorder. C1 [Simpson, Elizabeth A.; Paukner, Annika; Suomi, Stephen J.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, NIH, Comparat Ethol Lab, Poolesville, MD 20837 USA. [Simpson, Elizabeth A.; Sclafani, Valentina; Ferrari, Pier Francesco] Univ Parma, Dipartimento Neurosci, I-43100 Parma, Italy. [Hamel, Amanda F.; Novak, Melinda A.; Meyer, Jerrold S.] Univ Massachusetts, Dept Psychol, Amherst, MA 01003 USA. RP Simpson, EA (reprint author), Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, NIH, Comparat Ethol Lab, Poolesville, MD 20837 USA. EM simpsonea@mail.nih.gov OI Meyer, Jerrold/0000-0002-8382-7075; Simpson, Elizabeth/0000-0003-2715-2533 FU Division of Intramural Research, Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD), NICHD [P01HD064653]; National Institutes of Health [RR11122] FX We thank Ruth Woodward and Angela Ruggiero for technical assistance administering oxytocin and collecting saliva. We thank Lydia Martin, Grace Maloney, and Chris Catalfamo for behavioral reliability coding. Thanks to Nathan Fox for feedback on an earlier version of this paper. The Division of Intramural Research, Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD), NICHD Grant P01HD064653 (to P.F.F.), and National Institutes of Health Grant RR11122 (to M.A.N.) supported this research. NR 76 TC 23 Z9 23 U1 5 U2 44 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD MAY 13 PY 2014 VL 111 IS 19 BP 6922 EP 6927 DI 10.1073/pnas.1402471111 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA AH0GS UT WOS:000335798000049 PM 24778211 ER PT J AU Chagas, AC Ramirez, JL Jasinskiene, N James, AA Ribeiro, JMC Marinotti, O Calvo, E AF Chagas, Andrezza Campos Ramirez, Jose Luis Jasinskiene, Nijole James, Anthony A. Ribeiro, Jose M. C. Marinotti, Osvaldo Calvo, Eric TI Collagen-binding protein, Aegyptin, regulates probing time and blood feeding success in the dengue vector mosquito, Aedes aegypti SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE hematophagy; evolution; saliva; transgenesis; RNAi ID SALIVARY-GLAND PROTEIN; YELLOW-FEVER MOSQUITO; VON-WILLEBRAND-FACTOR; PLATELET-FUNCTION; ANOPHELES; GENE; DISEASE; AGGREGATION; ACTIVATION; INSIGHT AB Mosquito salivary glands have important roles in blood feeding and pathogen transmission. However, the biological relevance of many salivary components has yet to be determined. Aegyptin, a secreted salivary protein from Aedes aegypti, binds collagen and inhibits platelet aggregation and adhesion. We used a transgenic approach to study the relevance of Aegyptin in mosquito blood feeding. Aedes aegypti manipulated genetically to express gene-specific inverted-repeat RNA sequences exhibited significant reductions in Aegyptin mRNA accumulation (85-87%) and protein levels (>80-fold) in female mosquito salivary glands. Transgenic mosquitoes had longer probing times (78-300 s, P < 0.0001) when feeding on mice compared with controls (15-56 s), feeding success was reduced, and those feeding took smaller blood meals. However, no differences in feeding success or blood meal size were found in membrane feeding experiments using defibrinated human blood. Salivary gland extracts from transgenic mosquitoes failed to inhibit collagen-induced platelet aggregation in vitro. Reductions of Aegyptin did not affect salivary ADP-induced platelet aggregation inhibition or disturb anticlotting activities. Our results demonstrate the relevance of Aegyptin for A. aegypti blood feeding, providing further support for the hypothesis that platelet aggregation inhibition is a vital salivary function in blood feeding arthropods. It has been suggested that the multiple mosquito salivary components mediating platelet aggregation (i.e., Aegyptin, apyrase, D7) represent functional redundancy. Our findings do not support this hypothesis; instead, they indicate that multiple salivary components work synergistically and are necessary to achieve maximum blood feeding efficiency. C1 [Chagas, Andrezza Campos; Ramirez, Jose Luis; Ribeiro, Jose M. C.; Calvo, Eric] NIAID, Lab Malaria & Vector Res, Rockville, MD 20852 USA. [Jasinskiene, Nijole; James, Anthony A.; Marinotti, Osvaldo] Univ Calif Irvine, Dept Mol Biol & Biochem, Irvine, CA 92697 USA. [James, Anthony A.] Univ Calif Irvine, Dept Microbiol & Mol Genet, Irvine, CA 92697 USA. RP Marinotti, O (reprint author), Univ Calif Irvine, Dept Mol Biol & Biochem, Irvine, CA 92697 USA. EM omarinot@uci.edu; ecalvo@niaid.nih.gov RI Ribeiro, Jose/J-7011-2015; OI Marinotti, Osvaldo/0000-0002-7173-7160; Calvo, Eric/0000-0001-7880-2730; Ribeiro, Jose/0000-0002-9107-0818 FU Intramural Research Program of the Division of Intramural Research, NIAID, NIH; NIH NIAID [AI29746] FX We thank V. M. Pham for technical support; Judy Coleman, Aniko Fazekas, Andre Laughinghouse, and Kevin Lee for expert mosquito care; DTM/National Institutes of Health (NIH) for providing platelet-rich plasma; and Brenda Marshall [Department of Public Social Services, Division of Intramural Research, National Institute of Allergy and Infectious Diseases (NIAID)] for editorial assistance. This work was supported by the Intramural Research Program of the Division of Intramural Research, NIAID, NIH. O.M., N.J., and A.A.J. were supported in part by NIH NIAID Grant AI29746. NR 38 TC 4 Z9 4 U1 1 U2 24 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 MAY 13 PY 2014 VL 111 IS 19 BP 6946 EP 6951 DI 10.1073/pnas.1404179111 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA AH0GS UT WOS:000335798000053 PM 24778255 ER PT J AU Kaila, VRI Wikstrom, M Hummer, G AF Kaila, Ville R. I. Wikstrom, Marten Hummer, Gerhard TI Electrostatics, hydration, and proton transfer dynamics in the membrane domain of respiratory complex I SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE biological energy conversion; proton pumping; Grotthuss mechanism; QM/MM ID COUPLED ELECTRON-TRANSFER; CYTOCHROME-C-OXIDASE; NADH-QUINONE OXIDOREDUCTASE; MOLECULAR-MECHANISM; HYDROPHILIC DOMAIN; CRYSTAL-STRUCTURE; ENERGETICS; CHAIN; PUMP; TRANSLOCATION AB Complex I serves as the primary electron entry point into the mitochondrial and bacterial respiratory chains. It catalyzes the reduction of quinones by electron transfer from NADH, and couples this exergonic reaction to the translocation of protons against an electrochemical proton gradient. The membrane domain of the enzyme extends similar to 180 angstrom from the site of quinone reduction to the most distant proton pathway. To elucidate possible mechanisms of the long-range proton-coupled electron transfer process, we perform large-scale atomistic molecular dynamics simulations of the membrane domain of complex I from Escherichia coli. We observe spontaneous hydration of a putative proton entry channel at the NuoN/K interface, which is sensitive to the protonation state of buried glutamic acid residues. In hybrid quantum mechanics/classical mechanics simulations, we find that the observed water wires support rapid proton transfer from the protein surface to the center of the membrane domain. To explore the functional relevance of the pseudosymmetric inverted-repeat structures of the antiporter-like subunits NuoL/M/N, we constructed a symmetry-related structure of a possible alternate-access state. In molecular dynamics simulations, we find the resulting structural changes to be metastable and reversible at the protein backbone level. However, the increased hydration induced by the conformational change persists, with water molecules establishing enhanced lateral connectivity and pathways for proton transfer between conserved ionizable residues along the center of the membrane domain. Overall, the observed water-gated transitions establish conduits for the unidirectional proton translocation processes, and provide a possible coupling mechanism for the energy transduction in complex I. C1 [Kaila, Ville R. I.] Tech Univ Munich, Dept Chem, D-85748 Garching, Germany. [Kaila, Ville R. I.; Hummer, Gerhard] NIDDK, Chem Phys Lab, NIH, Bethesda, MD 20892 USA. [Wikstrom, Marten] Univ Helsinki, Inst Biotechnol, Helsinki Bioenerget Grp, FI-00014 Helsinki, Finland. [Hummer, Gerhard] Max Planck Inst Biophys, Dept Theoret Biophys, D-60438 Frankfurt, Germany. RP Kaila, VRI (reprint author), Tech Univ Munich, Dept Chem, D-85748 Garching, Germany. EM ville.kaila@ch.tum.de; gerhard.hummer@biophys.mpg.de RI Hummer, Gerhard/A-2546-2013 OI Hummer, Gerhard/0000-0001-7768-746X FU National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health; Max Planck Society; European Molecular Biology Organization Long-Term Fellowship; Sigrid Juselius Foundation; Biocentrum Helsinki; Academy of Finland FX We thank the high-performance Biowulf cluster (http://biowulf.nih.gov) at the National Institutes of Health for computer time. This work was supported by the Intramural Research Program of the National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health (V. R. I. K. and G. H); the Max Planck Society (G. H.); a European Molecular Biology Organization Long-Term Fellowship (to V. R. I. K.); and by grants from the Sigrid Juselius Foundation, Biocentrum Helsinki, and the Academy of Finland (all to M.W.). NR 46 TC 31 Z9 31 U1 4 U2 55 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 MAY 13 PY 2014 VL 111 IS 19 BP 6988 EP 6993 DI 10.1073/pnas.1319156111 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA AH0GS UT WOS:000335798000060 PM 24778264 ER PT J AU Cillo, AR Sobolewski, MD Bosch, RJ Fyne, E Piatak, M Coffin, JM Mellors, JW AF Cillo, Anthony R. Sobolewski, Michele D. Bosch, Ronald J. Fyne, Elizabeth Piatak, Michael, Jr. Coffin, John M. Mellors, John W. TI Quantification of HIV-1 latency reversal in resting CD4(+) T cells from patients on suppressive antiretroviral therapy SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE HIV-1 persistence; HIV-1 eradication; HIV-1 cure; fractional provirus expression ID RALTEGRAVIR INTENSIFICATION; INFECTED INDIVIDUALS; PLASMA VIREMIA; RESERVOIR; PERSISTENCE; EXPRESSION; MARKERS; DNA AB Reversal of proviral latency is being pursued as a curative strategy for HIV-1 infection. Recent clinical studies of in vivo administration of the histone deacetylase inhibitor suberoylanilide hydroxamic acid (SAHA; vorinostat) show increases in unspliced cellular HIV-1 RNA levels in resting CD4(+) T cells. A critical unknown, however, is the proportion of latent proviruses that can be transcriptionally reactivated by SAHA or T-cell activation. In this study, we quantified the fraction of HIV-1 proviruses in resting CD4(+) T cells from patients on suppressive antiretroviral therapy that were reactivated ex vivo with SAHA or antibodies to CD3/CD28. At concentrations of SAHA achieved clinically, only 0.079% of proviruses in resting CD4(+) T cells were reactivated to produce virions, compared with 1.5% of proviruses in cells treated with anti-CD3/CD28 antibodies after correcting for spontaneous virion production in the medium control. A significant positive correlation (rho = 0.67, P < 0.001) was found between levels of virions in the supernatant and unspliced cellular HIV-1 RNA following anti-CD3/CD28 treatment, but not following SAHA treatment (rho = 0.21, P = 0.99). These results reveal that the majority of HIV-1 proviruses are not reactivated by current therapeutic approaches and that more effective means of reversing proviral latency will likely be required to deplete HIV-1 reservoirs. C1 [Cillo, Anthony R.; Sobolewski, Michele D.; Fyne, Elizabeth; Mellors, John W.] Univ Pittsburgh, Sch Med, Div Infect Dis, Pittsburgh, PA 15261 USA. [Bosch, Ronald J.] Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA. [Piatak, Michael, Jr.] NCI, AIDS & Canc Virus Program, SAIC Freder Inc, Frederick, MD 21702 USA. [Coffin, John M.] Tufts Univ, Sch Med, Dept Mol Biol & Microbiol, Boston, MA 02111 USA. RP Coffin, JM (reprint author), Tufts Univ, Sch Med, Dept Mol Biol & Microbiol, Boston, MA 02111 USA. EM john.coffin@tufts.edu; jwm1@pitt.edu FU Pitt AIDS Research Training Program [5 T32 AI065380-08]; Science Applications and International Corporation (SAIC) through the National Cancer Institute [25XS119]; F. M. Kirby Foundation FX We thank the volunteers for participating in this study. Funding was provided by the Pitt AIDS Research Training Program 5 T32 AI065380-08 and Science Applications and International Corporation (SAIC) Contract 25XS119 through the National Cancer Institute. J.M.C. was a research professor of the American Cancer Society with support from the F. M. Kirby Foundation. NR 36 TC 71 Z9 71 U1 1 U2 16 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 MAY 13 PY 2014 VL 111 IS 19 BP 7078 EP 7083 DI 10.1073/pnas.1402873111 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA AH0GS UT WOS:000335798000075 PM 24706775 ER PT J AU Safronetz, D Prescott, J Feldmann, F Haddock, E Rosenke, R Okumura, A Brining, D Dahlstrom, E Porcella, SF Ebihara, H Scott, DP Hjelle, B Feldmann, H AF Safronetz, David Prescott, Joseph Feldmann, Friederike Haddock, Elaine Rosenke, Rebecca Okumura, Atsushi Brining, Douglas Dahlstrom, Eric Porcella, Stephen F. Ebihara, Hideki Scott, Dana P. Hjelle, Brian Feldmann, Heinz TI Pathophysiology of hantavirus pulmonary syndrome in rhesus macaques SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE New World hantaviruses; emerging pathogen; disease modeling ID SIN-NOMBRE-VIRUS; PUUMALA HANTAVIRUS; CARDIOPULMONARY SYNDROME; ANDES VIRUS; CYNOMOLGUS MACAQUES; INCUBATION PERIOD; IMMUNE-RESPONSE; CELL-CULTURE; S-SEGMENT; INFECTION AB The pathophysiology of hantavirus pulmonary syndrome (HPS) remains unclear because of a lack of surrogate disease models with which to perform pathogenesis studies. Nonhuman primates (NHP) are considered the gold standard model for studying the underlying immune activation/suppression associated with immunopathogenic viruses such as hantaviruses; however, to date an NHP model for HPS has not been described. Here we show that rhesus macaques infected with Sin Nombre virus (SNV), the primary etiological agent of HPS in North America, propagated in deer mice develop HPS, which is characterized by thrombocytopenia, leukocytosis, and rapid onset of respiratory distress caused by severe interstitial pneumonia. Despite establishing a systemic infection, SNV differentially activated host responses exclusively in the pulmonary endothelium, potentially the mechanism leading to acute severe respiratory distress. This study presents a unique chronological characterization of SNV infection and provides mechanistic data into the pathophysiology of HPS in a closely related surrogate animal model. We anticipate this model will advance our understanding of HPS pathogenesis and will greatly facilitate research toward the development of effective therapeutics and vaccines against hantaviral diseases. C1 [Safronetz, David; Prescott, Joseph; Haddock, Elaine; Ebihara, Hideki; Feldmann, Heinz] NIAID, Lab Virol, Rocky Mt Lab Res Technol Sect, Rocky Mt Labs,Div Intramural Res,NIH, Hamilton, MT 59840 USA. [Feldmann, Friederike; Rosenke, Rebecca; Brining, Douglas; Scott, Dana P.] NIAID, Rocky Mt Vet Branch, Rocky Mt Lab Res Technol Sect, Rocky Mt Labs,Div Intramural Res,NIH, Hamilton, MT 59840 USA. [Dahlstrom, Eric; Porcella, Stephen F.] NIAID, Genom Unit, Rocky Mt Lab Res Technol Sect, Rocky Mt Labs,Div Intramural Res,NIH, Hamilton, MT 59840 USA. [Okumura, Atsushi] Univ Washington, Dept Microbiol, Seattle, WA 98195 USA. [Hjelle, Brian] Univ New Mexico Hlth Sci Ctr, Dept Pathol, Ctr Infect Dis & Immun, Albuquerque, NM 87131 USA. [Feldmann, Heinz] Univ Manitoba, Dept Med Microbiol, Winnipeg, MB R3E 0J9, Canada. RP Feldmann, H (reprint author), NIAID, Lab Virol, Rocky Mt Lab Res Technol Sect, Rocky Mt Labs,Div Intramural Res,NIH, Hamilton, MT 59840 USA. EM feldmannh@niaid.nih.gov RI Okumura, Atsushi/E-8012-2015 OI Okumura, Atsushi/0000-0002-7779-3059 FU Division of Intramural Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health FX We thank Edward Schreckendgust, Rocky Rivera, Sandy Skorupa, Kathleen Meuchel, Jayne Faris, Amanda Weidow, Rachael LaCasse, Kimberly Meade-White, Tina Thomas, Dan Long, Shelly Robertson, Aaron Carmody, Sarah L. Anzick, Stacy M. Ricklefs, and Dan Bruno for scientific discussions and technical assistance and Anita Mora and Heather Murphy for preparing the graphics. This study was financially supported by the Division of Intramural Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health. NR 44 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 MAY 13 PY 2014 VL 111 IS 19 BP 7114 EP 7119 DI 10.1073/pnas.1401998111 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA AH0GS UT WOS:000335798000081 PM 24778254 ER PT J AU Wuchty, S AF Wuchty, Stefan TI Controllability in protein interaction networks SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID PHOSPHORYLATION NETWORKS; INTERACTION MAP; YEAST; RESOURCE; EVOLUTIONARY; DATABASE AB Recently, the focus of network research shifted to network controllability, prompting us to determine proteins that are important for the control of the underlying interaction webs. In particular, we determined minimum dominating sets of proteins (MDSets) in human and yeast protein interaction networks. Such groups of proteins were defined as optimized subsets where each non-MDSet protein can be reached by an interaction from an MDSet protein. Notably, we found that MDSet proteins were enriched with essential, cancer-related, and virus-targeted genes. Their central position allowed MDSet proteins to connect protein complexes and to have a higher impact on network resilience than hub proteins. As for their involvement in regulatory functions, MDSet proteins were enriched with transcription factors and protein kinases and were significantly involved in bottleneck interactions, regulatory links, phosphorylation events, and genetic interactions. C1 [Wuchty, Stefan] NIH, Natl Ctr Biotechnol Informat, Natl Lib Med, Bethesda, MD 20892 USA. RP Wuchty, S (reprint author), Univ Miami, Dept Comp Sci, Coral Gables, FL 33146 USA. EM wuchtys@cs.miami.edu FU National Institutes of Health/Department of Health and Human Services (Intramural Research program of the National Library of Medicine); Department of Computer Science at the University of Miami FX We thank A.-L. Barabasi, Peter Uetz, and Sawsan Khouri for fruitful discussions. This work was supported by the National Institutes of Health/Department of Health and Human Services (Intramural Research program of the National Library of Medicine) as well as start-up funds from the Department of Computer Science at the University of Miami. NR 32 TC 50 Z9 51 U1 3 U2 33 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 MAY 13 PY 2014 VL 111 IS 19 BP 7156 EP 7160 DI 10.1073/pnas.1311231111 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA AH0GS UT WOS:000335798000088 PM 24778220 ER PT J AU Fujiwara, I Remmert, K Piszczek, G Hammer, JA AF Fujiwara, Ikuko Remmert, Kirsten Piszczek, Grzegorz Hammer, John A. TI Capping protein regulatory cycle driven by CARMIL and V-1 may promote actin network assembly at protruding edges SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE cell migration; VASP ID FILAMENT BARBED END; HOMOLOGY DOMAIN 3; ARP2/3 COMPLEX; MOTILITY; NUCLEATION; POLYMERIZATION; MECHANISM; DYNAMICS; PROFILIN; THYMOSIN-BETA-4 AB Although capping protein (CP) terminates actin filament elongation, it promotes Arp2/3-dependent actin network assembly and accelerates actin-based motility both in vitro and in vivo. In vitro, capping protein Arp2/3 myosin I linker (CARMIL) antagonizes CP by reducing its affinity for the barbed end and by uncapping CP-capped filaments, whereas the protein V-1/myotrophin sequesters CP in an inactive complex. Previous work showed that CARMIL can readily retrieve CP from the CP:V-1 complex, thereby converting inactive CP into a version with moderate affinity for the barbed end. Here we further clarify the mechanism of this exchange reaction, and we demonstrate that the CP:CARMIL complex created by complex exchange slows the rate of barbed-end elongation by rapidly associating with, and dissociating from, the barbed end. Importantly, the cellular concentrations of V-1 and CP determined here argue that most CP is sequestered by V-1 at steady state in vivo. Finally, we show that CARMIL is recruited to the plasma membrane and only at cell edges undergoing active protrusion. Assuming that CARMIL is active only at this location, our data argue that a large pool of freely diffusing, inactive CP (CP:V-1) feeds, via CARMIL-driven complex exchange, the formation of weak-capping complexes (CP:CARMIL) at the plasma membrane of protruding edges. In vivo, therefore, CARMIL should promote Arp2/3-dependent actin network assembly at the leading edge by promoting barbed-end capping there. C1 [Fujiwara, Ikuko; Remmert, Kirsten; Hammer, John A.] NHLBI, Cell Biol & Physiol Ctr, NIH, Bethesda, MD 20892 USA. [Piszczek, Grzegorz] NHLBI, Ctr Biophys, NIH, Bethesda, MD 20892 USA. RP Hammer, JA (reprint author), NHLBI, Cell Biol & Physiol Ctr, NIH, Bldg 10, Bethesda, MD 20892 USA. EM hammerj@nhlbi.nih.gov NR 43 TC 18 Z9 18 U1 0 U2 4 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD MAY 13 PY 2014 VL 111 IS 19 BP E1970 EP E1979 DI 10.1073/pnas.1313738111 PG 10 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA AH0GS UT WOS:000335798000010 PM 24778263 ER PT J AU Li, WD Chen, CH Saud, SM Geng, L Zhang, G Liu, R Hua, BJ AF Li, Weidong Chen, Cihui Saud, Shakir M. Geng, Liang Zhang, Ge Liu, Rui Hua, Baojin TI Fei-Liu-Ping ointment inhibits lung cancer growth and invasion by suppressing tumor inflammatory microenvironment SO BMC COMPLEMENTARY AND ALTERNATIVE MEDICINE LA English DT Article DE Lung cancer; Fei-Liu-Ping ointment; Nuclear factor kappa light chain enhancer of activated B cells; Inflammation; Invasion; Epithelial mesenchymal transition; Cyclophosphamide ID NF-KAPPA-B; EPITHELIAL-MESENCHYMAL TRANSITIONS; CHINESE MEDICINE; DRUG DEVELOPMENT; UP-REGULATION; INVASIVENESS; PHARMACOLOGY; MACROPHAGES; PROGRESSION; METASTASIS AB Background: Lung cancer is one of the leading causes of cancer-related mortality worldwide. Conventional chemotherapy and radiotherapy are the primary therapeutic methods for lung cancer with the use of combination therapies gaining popularity. The frequency and duration of treatment, as well as, managing lung cancer by targeting multiple aspects of cancer biology is often limited by toxicity to the patient. There are many naturally occurring anticancer agents that have a high degree of efficacy and low toxicity, offering a viable and safe approach for the treatment of lung cancer. The herbs traditionally used in Chinese medicine for anticancer treatment offer great potential to enhance the efficacy of conventional therapy. In this study, we evaluated the synergistic effects of Fei-Liu-Ping (FLP) ointment in treating lung cancer; a known anticancer Chinese herbal based formula. Methods: In this study, A549 human lung carcinoma cell line and Lewis lung carcinoma xenograft mouse model were used. In addition, we utilized an in vitro co-culture system to simulate the tumor microenvironment in order to evaluate the molecular mechanisms of FLP treatment. Results: FLP treatment significantly inhibited tumor growth in the Lewis lung xenograft by 40 percent, compared to that of cyclophosphamide (CTX) of 62.02 percent. Moreover, combining FLP and CTX inhibited tumor growth by 83.23 percent. Upon evaluation, we found that FLP treatment reduced the concentration of serum pro-inflammatory cytokines IL-6, TNF-alpha, and IL-1 beta. In addition, we also found an improvement in E-cadherin expression and inhibition of N-cadherin and MMP9. We found similar findings in vitro when we co-cultured A549 cells with macrophages. FLP treatment inhibited A549 cell growth, invasion and metastasis, in part, through the regulation of NF-kappa B and altering the expression of E-cadherin, N-cadherin, MMP2 and MMP9. Conclusions: FLP exerts anti-inflammatory properties in the tumor microenvironment, which may contribute to its anticancer effects. FLP treatment may be a promising therapy for inflammation associated lung cancer treatment alone, or in combination with conventional therapies and may prevent lung cancer metastasis. C1 [Li, Weidong; Zhang, Ge; Liu, Rui; Hua, Baojin] China Acad Chinese Med Sci, Guanganmen Hosp, Dept Oncol, Beijing 100053, Peoples R China. [Chen, Cihui] TCM, Zhejiang Prov Hosp, Dept Oncol, Hangzhou 310006, Zhejiang, Peoples R China. [Saud, Shakir M.] NCI, Nutr Sci Res Grp, Canc Prevent Div, NIH, Rockville, MD 21702 USA. [Geng, Liang] Zhengzhou Univ, Henan Canc Hosp, Zhengzhou 450003, Henan, Peoples R China. RP Hua, BJ (reprint author), China Acad Chinese Med Sci, Guanganmen Hosp, Dept Oncol, Beijing 100053, Peoples R China. EM dr.huabaojin@hotmail.com FU National Natural Science Foundation of China [81273718, 81102587, 2012T50199, 20110490559]; Ministry of Science and Technology of the People's Republic of China [2010ZX09102-216] FX We thank all the researchers who were involved in this study and we thank Dr. Matthew R. Young for reviewing and revising this manuscript. We also thank Xin Qi and Yingxia Pei for technical assistance. We also thank Bingkui Piao for theory guidance of Chinese Medicine. This study was supported by the grant from National Natural Science Foundation of China. (No. 81273718; No. 81102587, No. 2012T50199, No. 20110490559) and from Ministry of Science and Technology of the People's Republic of China. (No. 2010ZX09102-216). NR 40 TC 7 Z9 10 U1 1 U2 9 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1472-6882 J9 BMC COMPLEM ALTERN M JI BMC Complement. Altern. Med. PD MAY 12 PY 2014 VL 14 AR 153 DI 10.1186/1472-6882-14-153 PG 12 WC Integrative & Complementary Medicine SC Integrative & Complementary Medicine GA AI4TI UT WOS:000336857300001 PM 24885825 ER PT J AU Evans, DS Calton, MA Kim, MJ Kwok, PY Miljkovic, I Harris, T Koster, A Liu, YM Tranah, GJ Ahituv, N Hsueh, WC Vaisse, C AF Evans, Daniel S. Calton, Melissa A. Kim, Mee J. Kwok, Pui-Yan Miljkovic, Iva Harris, Tamara Koster, Annemarie Liu, Yongmei Tranah, Gregory J. Ahituv, Nadav Hsueh, Wen-Chi Vaisse, Christian TI Genetic Association Study of Adiposity and Melanocortin-4 Receptor (MC4R) Common Variants: Replication and Functional Characterization of Non-Coding Regions SO PLOS ONE LA English DT Article ID GENOME-WIDE ASSOCIATION; BODY-MASS INDEX; NERVOUS-SYSTEM; ADULT OBESITY; LOCI; INDIVIDUALS; POLYMORPHISMS; METAANALYSIS; MUTATIONS; AFRICAN AB Common genetic variants 3 ' of MC4R within two large linkage disequilibrium (LD) blocks spanning 288 kb have been associated with common and rare forms of obesity. This large association region has not been refined and the relevant DNA segments within the association region have not been identified. In this study, we investigated whether common variants in the MC4R gene region were associated with adiposity-related traits in a biracial population-based study. Single nucleotide polymorphisms (SNPs) in the MC4R region were genotyped with a custom array and a genome-wide array and associations between SNPs and five adiposity-related traits were determined using race-stratified linear regression. Previously reported associations between lower BMI and the minor alleles of rs2229616/Val103lle and rs52820871/lle251Leu were replicated in white female participants. Among white participants, rs11152221 in a proximal 3 ' LD block (closer to MC4R) was significantly associated with multiple adiposity traits, but SNPs in a distal 3 ' LD block (farther from MC4R) were not. In a case-control study of severe obesity, rs11152221 was significantly associated. The association results directed our follow-up studies to the proximal LD block downstream of MC4R. By considering nucleotide conservation, the significance of association, and proximity to the MC4R gene, we identified a candidate MC4R regulatory region. This candidate region was sequenced in 20 individuals from a study of severe obesity in an attempt to identify additional variants, and the candidate region was tested for enhancer activity using in vivo enhancer assays in zebrafish and mice. Novel variants were not identified by sequencing and the candidate region did not drive reporter gene expression in zebrafish or mice. The identification of a putative insulator in this region could help to explain the challenges faced in this study and others to link SNPs associated with adiposity to altered MC4R expression. C1 [Evans, Daniel S.; Tranah, Gregory J.] Calif Pacific Med Ctr Res Inst, San Francisco, CA USA. [Calton, Melissa A.; Hsueh, Wen-Chi; Vaisse, Christian] Univ Calif San Francisco, Ctr Diabet, San Francisco, CA 94143 USA. [Calton, Melissa A.; Hsueh, Wen-Chi; Vaisse, Christian] Univ Calif San Francisco, Dept Med, San Francisco, CA 94143 USA. [Kim, Mee J.] Univ Calif San Francisco, Dept Bioengn & Therapeut Sci, San Francisco, CA 94143 USA. [Kim, Mee J.] Univ Calif San Francisco, Inst Human Genet, San Francisco, CA 94143 USA. [Kwok, Pui-Yan] Univ Calif San Francisco, Inst Cardiovasc Res, Inst Human Genet, San Francisco, CA 94143 USA. [Kwok, Pui-Yan] Univ Calif San Francisco, Dept Dermatol, San Francisco, CA 94143 USA. [Miljkovic, Iva] Univ Pittsburgh, Dept Epidemiol, Pittsburgh, PA 15261 USA. [Harris, Tamara; Koster, Annemarie] NIA, Bethesda, MD 20892 USA. [Liu, Yongmei] Wake Forest Univ, Dept Epidemiol & Prevent, Div Publ Hlth Sci, Winston Salem, NC 27109 USA. RP Vaisse, C (reprint author), Univ Calif San Francisco, Ctr Diabet, San Francisco, CA 94143 USA. EM vaisse@diabetes.ucsf.edu RI Koster, Annemarie/E-7438-2010; OI Miljkovic, Iva/0000-0002-3155-9777; Ahituv, Nadav/0000-0002-7434-8144 FU Intramural Research Program of the NIH; National Institute on Aging (NIA) [N01-AG-6-2101, N01-AG-6-2103, N01-AG-6-2106, R01-AG028050]; NINR [R01-NR012459]; NIDDK [1R01DK090382, R01DK060540]; NIA [1R01AG032098-01A1]; National Institutes of Health [HHSN268200782096C]; NIH [T32 DK007418, T32 GM007175]; Pharmaceutical Sciences and Pharmacogenomics; Amgen Research Excellence in Bioengineering and Therapeutic Sciences Fellowship FX This research was supported in part by the Intramural Research Program of the NIH, National Institute on Aging (NIA), and by NIA contracts N01-AG-6-2101, N01-AG-6-2103, N01-AG-6-2106, NIA grant R01-AG028050, NINR grant R01-NR012459, and NIDDK grants 1R01DK090382 and R01DK060540. 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. DSE was supported by NIH training grant T32 DK007418. MAC was supported by NIH training grant T32 GM007175, Pharmaceutical Sciences and Pharmacogenomics. MJK was supported in part by NIH training grant T32 GM007175 and the Amgen Research Excellence in Bioengineering and Therapeutic Sciences Fellowship. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 51 TC 3 Z9 3 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 MAY 12 PY 2014 VL 9 IS 5 AR e96805 DI 10.1371/journal.pone.0096805 PG 13 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA AI1ZC UT WOS:000336653300033 PM 24820477 ER PT J AU Narjoz, C Favre, A McMullen, J Kiehl, P Montemurro, M Figg, WD Beaune, P de Waziers, I Rochat, B AF Narjoz, Celine Favre, Amelie McMullen, Justin Kiehl, Philippe Montemurro, Michael Figg, William D. Beaune, Philippe de Waziers, Isabelle Rochat, Bertrand TI Important Role of CYP2J2 in Protein Kinase Inhibitor Degradation: A Possible Role in Intratumor Drug Disposition and Resistance SO PLOS ONE LA English DT Article ID CYTOCHROME-P450 2J2; ANTICANCER AGENTS; MOLECULAR-MECHANISMS; MASS-SPECTROMETRY; OVARIAN-CANCER; LUNG-CANCER; IMATINIB; METABOLISM; EXPRESSION; IDENTIFICATION AB We have investigated in vitro the metabolic capability of 3 extrahepatic cytochromes P-450, CYP1A1, 1B1 and 2J2, known to be over-expressed in various tumors, to biotransform 5 tyrosine kinase inhibitors (TKI): dasatinib, imatinib, nilotinib, sorafenib and sunitinib. Moreover, mRNA expression of CYP1A1, 1B1, 2J2 and 3A4 in 6 hepatocellular and 14 renal cell carcinoma tumor tissues and their surrounding healthy tissues, was determined. Our results show that CYP1A1, 1B1 and especially 2J2 can rapidly biotransform the studied TKIs with a metabolic efficiency similar to that of CYP3A4. The mRNA expression of CYP1A1, 1B1, 2J2 and 3A4 in tumor biopsies has shown i) the strong variability of CYP expression and ii) distinct outliers showing high expression levels (esp. CYP2J2) that are compatible with high intratumoral CYP activity and tumor-specific TKI degradation. CYP2J2 inhibition could be a novel clinical strategy to specifically increase the intratumoral rather than plasma TKI levels, improving TKI efficacy and extending the duration before relapse. Such an approach would be akin to beta-lactamase inhibition, a classical strategy to avoid antibiotic degradation and resistance. C1 [Narjoz, Celine; Beaune, Philippe; de Waziers, Isabelle] Univ Paris 05, INSERM UMR S U775, Sorbonne Paris Cite, Paris, France. [Narjoz, Celine; Beaune, Philippe] Hop Europeen Georges Pompidou, Serv Biochim, Unite Fonct Pharmacogenet & Oncol Mol, Paris, France. [Favre, Amelie; McMullen, Justin; Kiehl, Philippe; Rochat, Bertrand] CHU Vaudois, Quantitat Mass Spectrometry Facil, Lausanne, Switzerland. [Montemurro, Michael] Univ Zurich Hosp, CH-8091 Zurich, Switzerland. [Figg, William D.] NCI, Genitourinary Malignancies Branch, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. RP Rochat, B (reprint author), CHU Vaudois, Quantitat Mass Spectrometry Facil, Lausanne, Switzerland. EM bertrand.rochat@chuv.ch RI Figg Sr, William/M-2411-2016 NR 43 TC 3 Z9 4 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 MAY 12 PY 2014 VL 9 IS 5 AR e95532 DI 10.1371/journal.pone.0095532 PG 10 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA AI1ZC UT WOS:000336653300006 PM 24819355 ER PT J AU Pineda, S Milne, RL Calle, ML Rothman, N de Maturana, EL Herranz, J Kogevinas, M Chanock, SJ Tardon, A Marquez, M Guey, LT Garcia-Closas, M Lloreta, J Baum, E Gonzalez-Neira, A Carrato, A Navarro, A Silverman, DT Real, FX Malats, N AF Pineda, Silvia Milne, Roger L. Luz Calle, M. Rothman, Nathaniel Lopez de Maturana, Evangelina Herranz, Jesus Kogevinas, Manolis Chanock, Stephen J. Tardon, Adonina Marquez, Mirari Guey, Lin T. Garcia-Closas, Montserrat Lloreta, Josep Baum, Erin Gonzalez-Neira, Anna Carrato, Alfredo Navarro, Arcadi Silverman, Debra T. Real, Francisco X. Malats, Nuria TI Genetic Variation in the TP53 Pathway and Bladder Cancer Risk. A Comprehensive Analysis SO PLOS ONE LA English DT Article ID GENOME-WIDE ASSOCIATION; ARG72PRO POLYMORPHISM; URINARY-BLADDER; SUSCEPTIBILITY; METAANALYSIS; REGRESSION; MUTATIONS; NEOPLASMS; SELECTION; MARKERS AB Introduction: Germline variants in TP63 have been consistently associated with several tumors, including bladder cancer, indicating the importance of TP53 pathway in cancer genetic susceptibility. However, variants in other related genes, including TP53 rs1042522 (Arg72Pro), still present controversial results. We carried out an in depth assessment of associations between common germline variants in the TP53 pathway and bladder cancer risk. Material and Methods: We investigated 184 tagSNPs from 18 genes in 1,058 cases and 1,138 controls from the Spanish Bladder Cancer/EPICURO Study. Cases were newly-diagnosed bladder cancer patients during 1998-2001. Hospital controls were age-gender, and area matched to cases. SNPs were genotyped in blood DNA using Illumina Golden Gate and TaqMan assays. Cases were subphenotyped according to stage/grade and tumor p53 expression. We applied classical tests to assess individual SNP associations and the Least Absolute Shrinkage and Selection Operator (LASSO)-penalized logistic regression analysis to assess multiple SNPs simultaneously. Results: Based on classical analyses, SNPs in BAK1 (1), IGF1R (5), P53AIP1 (1), PMAIP1 (2), SERINPB5 (3), TP63 (3), and TP73 (1) showed significant associations at p-value <= 0.05. However, no evidence of association, either with overall risk or with specific disease subtypes, was observed after correction for multiple testing (p-value >= 0.8). LASSO selected the SNP rs6567355 in SERPINB5 with 83% of reproducibility. This SNP provided an OR = 1.21, 95% CI 1.05-1.38, p-value = 0.006, and a corrected p-value = 0.5 when controlling for over-estimation. Discussion: We found no strong evidence that common variants in the TP53 pathway are associated with bladder cancer susceptibility. Our study suggests that it is unlikely that TP53 Arg72Pro is implicated in the UCB in white Europeans. SERPINB5 and TP63 variation deserve further exploration in extended studies. C1 [Pineda, Silvia; Milne, Roger L.; Lopez de Maturana, Evangelina; Herranz, Jesus; Marquez, Mirari; Guey, Lin T.; Baum, Erin; Gonzalez-Neira, Anna; Real, Francisco X.; Malats, Nuria] Spanish Natl Canc Res Ctr CNIO, Madrid, Spain. [Luz Calle, M.] Univ Vic, Dept Syst Biol, Vic, Spain. [Rothman, Nathaniel; Chanock, Stephen J.; Garcia-Closas, Montserrat; Silverman, Debra T.] NCI, Div Canc Epidemiol & Genet, Dept Hlth & Human Serv, Bethesda, MD 20892 USA. [Kogevinas, Manolis] Ctr Res Environm Epidemiol CREAL, Barcelona, Spain. [Kogevinas, Manolis; Lloreta, Josep] Hosp del Mar, Inst Municipal Invest Med, Barcelona, Spain. [Tardon, Adonina] Univ Oviedo, Dept Prevent Med, Oviedo, Spain. [Lloreta, Josep] Hosp del Mar IMAS, Dept Patol, Barcelona, Spain. [Carrato, Alfredo] Hosp Univ Elche, Serv Oncol, Elche, Spain. [Carrato, Alfredo] Hosp Univ Ramon y Cajal, Serv Oncol, Madrid, Spain. [Navarro, Arcadi; Real, Francisco X.] Univ Pompeu Fabra, Dept Ciencies Expt & Salut, Barcelona, Spain. [Navarro, Arcadi] Inst Biol Evolut UPF CSIC, Barcelona, Spain. [Navarro, Arcadi] ICREA, Barcelona, Spain. [Navarro, Arcadi] Inst Nacl Bioinformat, Barcelona, Spain. RP Malats, N (reprint author), Spanish Natl Canc Res Ctr CNIO, Madrid, Spain. EM nmalats@cnio.es RI Lloreta, J/I-2112-2014; Navarro, Arcadi/F-1592-2011; Gonzalez-Neira, Anna/C-5791-2015; Calle, M.Luz/D-2704-2015; Kogevinas, Manolis/C-3918-2017; Herranz Valera, Jesus/M-8657-2014; Garcia-Closas, Montserrat /F-3871-2015; Malats, Nuria/H-7041-2015; Real Arribas, Francisco/H-5275-2015 OI Lloreta, J/0000-0003-1644-9470; Navarro, Arcadi/0000-0003-2162-8246; Calle, M.Luz/0000-0001-9334-415X; Lopez de Maturana, Evangelina/0000-0001-9425-3911; Herranz Valera, Jesus/0000-0002-7385-1311; Garcia-Closas, Montserrat /0000-0003-1033-2650; Malats, Nuria/0000-0003-2538-3784; Real Arribas, Francisco/0000-0001-9501-498X FU Fondo de Investigacion Sanitaria, Spain [00/0745, PI051436, PI061614, G03/174]; Red Tematica de Investigacion Cooperativa en Cancer, Spain [RD06/0020-RTICC]; Marato TV3 [050830]; European Commission [EU-FP7-HEALTH-F2-2008-201663-UROMOL]; US National Institutes of Health [USA-NIH-RO1-CA089715]; Intramural Research Program of the Division of Cancer Epidemiology and Genetics, National Cancer Institute at the National Institutes of Health, USA; Consolider ONCOBIO (Ministerio de Economia y Competitividad, Madrid, Spain) FX This work was supported by the Fondo de Investigacion Sanitaria, Spain (grant numbers 00/0745, PI051436, PI061614, G03/174); Red Tematica de Investigacion Cooperativa en Cancer (grant number RD06/0020-RTICC), Spain; Marato TV3 (grant number 050830); European Commission (grant numbers EU-FP7-HEALTH-F2-2008-201663-UROMOL; US National Institutes of Health (grant number USA-NIH-RO1-CA089715); and the Intramural Research Program of the Division of Cancer Epidemiology and Genetics, National Cancer Institute at the National Institutes of Health, USA; Consolider ONCOBIO (Ministerio de Economia y Competitividad, Madrid, Spain). 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 5 U1 2 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 MAY 12 PY 2014 VL 9 IS 5 AR e89952 DI 10.1371/journal.pone.0089952 PG 8 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA AI1ZC UT WOS:000336653300001 PM 24818791 ER PT J AU Masuelli, L Fantini, M Benvenuto, M Sacchetti, P Giganti, MG Tresoldi, I Lido, P Lista, F Cavallo, F Nanni, P Schlom, J Modesti, A Bei, R AF Masuelli, Laura Fantini, Massimo Benvenuto, Monica Sacchetti, Pamela Giganti, Maria Gabriella Tresoldi, Ilaria Lido, Paolo Lista, Florigio Cavallo, Federica Nanni, Patrizia Schlom, Jeffrey Modesti, Andrea Bei, Roberto TI Intratumoral delivery of recombinant vaccinia virus encoding for ErbB2/Neu inhibits the growth of salivary gland carcinoma cells SO JOURNAL OF TRANSLATIONAL MEDICINE LA English DT Article DE Vaccine; Cancer; Salivary glands; ErbB2/Neu; Vaccinia virus; Intratumor ID MULTIPLE ERBB RECEPTORS; ANTI-ERBB-2 MONOCLONAL-ANTIBODIES; CARCINOEMBRYONIC ANTIGEN CEA; PHASE-I TRIAL; IMMUNE-RESPONSES; PROSTATE-CANCER; BREAST-CANCER; COSTIMULATORY MOLECULES; POXVIRUS VACCINES; TRANSGENIC MICE AB Background: The antitumor activity induced by intratumoral vaccination with poxvirus expressing a tumor antigen was shown to be superior to that induced by subcutaneous vaccination. Salivary gland carcinomas overexpress ErbB2. Trastuzumab, a monoclonal antibody to ErbB2, was proposed for salivary gland tumors treatment. We explored the effectiveness of intratumoral vaccination with the recombinant vaccinia virus ErbB2/Neu (rV-neuT) vaccine in hampering the growth of transplanted Neu-overexpressing BALB-neuT salivary gland cancer cells (SALTO) in BALB-neuT mice. Methods: BALB-neuT male mice were subcutaneously injected with SALTO tumor cells and intratumorally vaccinated twice with different doses of either rV-neuT or V-wt (wild-type). Tumors were measured weekly. The presence of anti-ErbB2/Neu antibodies was assayed by ELISA, immunoprecipitation or indirect immunofluorescence. Biological activity of immune sera was investigated by analyzing antibody-dependent cellular cytotoxicity (ADCC), SALTO cells proliferation and apoptosis, ErbB2/Neu receptor down regulation and ERK1/2 phosphorylation. Anti-Neu T cell immunity was investigated by determining the release of IL-2 and IFN-gamma in T cells supernatant. Survival curves were determined using the Kaplan-Meier method and compared using the log-rank test. Differences in tumor volumes, number of apoptotic cells, titer of the serum, percentage of ADCC were evaluated through a two-tailed Student's t-test. Results: rV-neuT intratumoral vaccination was able to inhibit the growth of SALTO cancer cells in a dose-dependent manner. The anti-Neu serum titer paralleled in vivo antitumor activity of rV-neuT vaccinated mice. rV-neuT immune serum was able to mediate ADCC, inhibition of SALTO cells proliferation, down regulation of the ErbB2/Neu receptor, inhibition of ERK1/2 phosphorylation and induction of apoptosis, thus suggesting potential mechanisms of in vivo tumor growth interference. In addition, spleen T cells of rV-neuT vaccinated mice released IFN-gamma and IL-2 upon in vitro stimulation with several Neu-specific peptides located in the extracellular domain of Neu sequence. Conclusions: rV-neuT intratumoral vaccination could be employed to induce an efficient antitumor response and reject transplanted salivary gland tumors. Our findings may have important implications for the design of cancer vaccine protocols for the treatment of salivary gland tumors and other accessible tumors using intratumoral injection of recombinant vaccinia virus. C1 [Masuelli, Laura; Sacchetti, Pamela] Univ Roma La Sapienza, Dept Expt Med, I-00185 Rome, Italy. [Fantini, Massimo; Benvenuto, Monica; Giganti, Maria Gabriella; Tresoldi, Ilaria; Modesti, Andrea; Bei, Roberto] Univ Roma Tor Vergata, Dept Clin Sci & Translat Med, Rome, Italy. [Lido, Paolo] Univ Roma Tor Vergata, Internal Med Residency Program, Rome, Italy. [Lista, Florigio] Ctr Studi & Ric Sanita & Vet Esercito, Rome, Italy. [Cavallo, Federica] Univ Turin, Dept Mol Biotechnol & Hlth Sci, Ctr Mol Biotechnol, Turin, Italy. [Nanni, Patrizia] Univ Bologna, Dept Expt Diagnost & Specialty Med, Bologna, Italy. [Schlom, Jeffrey] NCI, Lab Tumor Immunol & Biol, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. RP Bei, R (reprint author), Univ Roma Tor Vergata, Dept Clin Sci & Translat Med, Rome, Italy. EM bei@med.uniroma2.it RI Cavallo, Federica/C-5666-2011; Benvenuto, Monica/K-2685-2016; OI Cavallo, Federica/0000-0003-4571-1060; Benvenuto, Monica/0000-0002-2520-1306; Nanni, Patrizia/0000-0001-5319-0803; Fantini, Massimo/0000-0002-8164-2587 FU PRIN FX This study was supported by a grant from PRIN (R. B). The authors wish to thank Barbara Bulgarini for help in manuscript preparation. We wish to thank Therion Biologics (Cambridge, MA) and Dr. G. Mazzara, which kindly provided vaccinia viruses, IRBM P. Angeletti (Pomezia, Rome) for peptides, and Dr. Eddi Di Marco (Istituto Tumori di Genova) for providing LTR-Neu cells. NR 71 TC 7 Z9 7 U1 0 U2 11 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 MAY 10 PY 2014 VL 12 AR 122 DI 10.1186/1479-5876-12-122 PG 14 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA AI5TQ UT WOS:000336932500002 PM 24886178 ER PT J AU Chen, BJ Qin, J AF Chen, Baojiang Qin, Jing TI Use of empirical likelihood to calibrate auxiliary information in partly linear monotone regression models SO STATISTICS IN MEDICINE LA English DT Article DE empirical likelihood; auxiliary information; missing data; isotonic regression ID ADDITIVE ISOTONIC REGRESSION; ESTIMATORS; ALGORITHM AB In statistical analysis, a regression model is needed if one is interested in finding the relationship between a response variable and covariates. When the response depends on the covariate, then it may also depend on the function of this covariate. If one has no knowledge of this functional form but expect for monotonic increasing or decreasing, then the isotonic regression model is preferable. Estimation of parameters for isotonic regression models is based on the pool-adjacent-violators algorithm (PAVA), where the monotonicity constraints are built in. With missing data, people often employ the augmented estimating method to improve estimation efficiency by incorporating auxiliary information through a working regression model. However, under the framework of the isotonic regression model, the PAVA does not work as the monotonicity constraints are violated. In this paper, we develop an empirical likelihood-based method for isotonic regression model to incorporate the auxiliary information. Because the monotonicity constraints still hold, the PAVA can be used for parameter estimation. Simulation studies demonstrate that the proposed method can yield more efficient estimates, and in some situations, the efficiency improvement is substantial. We apply this method to a dementia study. Copyright (c) 2013 John Wiley & Sons, Ltd. C1 [Chen, Baojiang] Univ Nebraska Med Ctr, Dept Biostat, Omaha, NE 68198 USA. [Qin, Jing] NIAID, NIH, Bethesda, MD 20892 USA. RP Chen, BJ (reprint author), Univ Nebraska Med Ctr, Dept Biostat, Omaha, NE 68198 USA. EM baojiang.chen@unmc.edu FU National Institute on Aging grant [U01AG016976]; National Institute on Aging [U01AG016976] FX The authors thank the two referees for their constructive comments and suggestions. Dr. Chen was supported in part by National Institute on Aging grant U01AG016976. The National Alzheimer's Coordinating Center database is supported by National Institute on Aging grant U01AG016976. NR 22 TC 0 Z9 0 U1 0 U2 7 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 MAY 10 PY 2014 VL 33 IS 10 BP 1713 EP 1722 DI 10.1002/sim.6057 PG 10 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 AE5KS UT WOS:000334028500006 PM 24323567 ER PT J AU Cadiz-Rivera, B Fromm, G de Vries, C Fields, J McGrath, KE Fiering, S Bulger, M AF Cadiz-Rivera, Brenda Fromm, George de Vries, Christina Fields, Jennifer McGrath, Kathleen E. Fiering, Steven Bulger, Michael TI The Chromatin "Landscape" of a Murine Adult beta-Globin Gene Is Unaffected by Deletion of Either the Gene Promoter or a Downstream Enhancer SO PLOS ONE LA English DT Article ID LOCUS-CONTROL REGION; HYPERSENSITIVE SITES; ERYTHROID-CELLS; TRANSCRIPTION; EXPRESSION; SENSITIVITY; ACTIVATION; LINKING; PATTERN; MICE AB In mammals, the complex tissue-and developmental-specific expression of genes within the beta-globin cluster is known to be subject to control by the gene promoters, by a locus control region (LCR) located upstream of the cluster, and by sequence elements located across the intergenic regions. Despite extensive investigation, however, the complement of sequences that is required for normal regulation of chromatin structure and gene expression within the cluster is not fully defined. To further elucidate regulation of the adult beta-globin genes, we investigate the effects of two deletions engineered within the endogenous murine beta-globin locus. First, we find that deletion of the beta 2-globin gene promoter, while eliminating b2-globin gene expression, results in no additional effects on chromatin structure or gene expression within the cluster. Notably, our observations are not consistent with competition among the beta-globin genes for LCR activity. Second, we characterize a novel enhancer located 3' of the beta 2-globin gene, but find that deletion of this sequence has no effect whatsoever on gene expression or chromatin structure. This observation highlights the difficulty in assigning function to enhancer sequences identified by the chromatin "landscape" or even by functional assays. C1 [Cadiz-Rivera, Brenda; Fromm, George; de Vries, Christina; McGrath, Kathleen E.; Bulger, Michael] Univ Rochester, Med Ctr, Dept Psychiat, Rochester, NY 14642 USA. [Cadiz-Rivera, Brenda; Fromm, George; de Vries, Christina; McGrath, Kathleen E.; Bulger, Michael] Ctr Pediat Biomed Res, Rochester, NY USA. [Fromm, George] NIEHS, NIH, Res Triangle Pk, NC 27709 USA. [Fields, Jennifer; Fiering, Steven] Dartmouth Coll, Hitchcock Med Ctr, Dartmouth Med Sch, Dept Microbiol & Immunol, Hanover, NH 03756 USA. RP Bulger, M (reprint author), Univ Rochester, Med Ctr, Dept Psychiat, Rochester, NY 14642 USA. EM michael_bulger@urmc.rochester.edu FU National Institutes of Health (NIH) [R01-DK070687-06A1]; Institutional Ruth L. Kirschstein National Research Service Award [GM068411] FX This work was supported by National Institutes of Health (NIH) R01-DK070687-06A1. G. F. and B.C.-R. were supported in part by grant number GM068411 from Institutional Ruth L. Kirschstein National Research Service Award. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 27 TC 0 Z9 0 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 MAY 9 PY 2014 VL 9 IS 5 AR e92947 DI 10.1371/journal.pone.0092947 PG 8 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA AI4LX UT WOS:000336838000003 PM 24817273 ER PT J AU Simari, RD Pepine, CJ Traverse, JH Henry, TD Bolli, R Spoon, DB Yeh, E Hare, JM Schulman, IH Anderson, RD Lambert, C Sayre, SL Taylor, DA Ebert, RF Moye, LA AF Simari, Robert D. Pepine, Carl J. Traverse, Jay H. Henry, Timothy D. Bolli, Roberto Spoon, Daniel B. Yeh, Ed Hare, Joshua M. Schulman, Ivonne Hernandez Anderson, R. David Lambert, Charles Sayre, Shelly L. Taylor, Doris A. Ebert, Ray F. Moye, Lemuel A. TI Bone Marrow Mononuclear Cell Therapy for Acute Myocardial Infarction A Perspective From the Cardiovascular Cell Therapy Research Network SO CIRCULATION RESEARCH LA English DT Article DE diagnostic imaging; myocardial infarction; population ID LEFT-VENTRICULAR FUNCTION; RANDOMIZED PHASE-1 TRIAL; HEMATOPOIETIC STEM-CELLS; ISCHEMIC CARDIOMYOPATHY; INTRACORONARY INJECTION; PROGENITOR CELLS; HEART-FAILURE; DELIVERY; CCTRN; METAANALYSIS AB To understand the role of bone marrow mononuclear cells in the treatment of acute myocardial infarction, this overview offers a retrospective examination of strengths and limitations of 3 contemporaneous trials with attention to critical design features and provides an analysis of the combined data set and implications for future directions in cell therapy for acute myocardial infarction. C1 [Simari, Robert D.; Spoon, Daniel B.] Mayo Clin, Rochester, MN USA. [Pepine, Carl J.; Anderson, R. David] Univ Florida, Sch Med, Gainesville, FL USA. [Traverse, Jay H.] Univ Minnesota, Sch Med, Abbott NW Hosp, Minneapolis Heart Inst, Minneapolis, MN 55455 USA. [Henry, Timothy D.] Cedars Sinai Heart Inst, Los Angeles, CA USA. [Bolli, Roberto] Univ Louisville, Sch Med, Louisville, KY 40292 USA. [Yeh, Ed] Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA. [Hare, Joshua M.; Schulman, Ivonne Hernandez] Univ Miami, Miller Sch Med, Coral Gables, FL 33124 USA. [Lambert, Charles] Florida Hosp Tampa Pepin Heart Inst, Tampa, FL USA. [Sayre, Shelly L.; Moye, Lemuel A.] Univ Texas Hlth Sci Ctr Houston, Sch Publ Hlth, Houston, TX 77030 USA. [Taylor, Doris A.] Texas Heart Inst, Houston, TX 77025 USA. [Ebert, Ray F.] NHLBI, Bethesda, MD 20892 USA. RP Moye, LA (reprint author), Univ Texas Sch Publ Hlth, Coordinating Ctr Clin Trials, 1200 Herman Pressler,E-1009, Houston, TX 77030 USA. EM Lemmoye@msn.com FU National Heart, Lung, and Blood Institute [UM1 HL087318-07] FX Funding for the Cardiovascular Cell Therapy Research Network was provided by the National Heart, Lung, and Blood Institute under cooperative agreement UM1 HL087318-07. NR 28 TC 25 Z9 25 U1 0 U2 7 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7330 EI 1524-4571 J9 CIRC RES JI Circ.Res. PD MAY 9 PY 2014 VL 114 IS 10 BP 1564 EP 1568 DI 10.1161/CIRCRESAHA.114.303720 PG 5 WC Cardiac & Cardiovascular Systems; Hematology; Peripheral Vascular Disease SC Cardiovascular System & Cardiology; Hematology GA AH2HF UT WOS:000335941400013 PM 24812350 ER PT J AU Hart, J Tillman, G Kraut, MA Chiang, HS Strain, JF Li, YF Agrawal, AG Jester, P Gnann, JW Whitley, RJ AF Hart, John, Jr. Tillman, Gail Kraut, Michael A. Chiang, Hsueh-Sheng Strain, Jeremy F. Li, Yufeng Agrawal, Amy G. Jester, Penny Gnann, John W., Jr. Whitley, Richard J. CA NIAID Collaborative Antiviral Stud West Nile Virus 2010 Protocol Team TI West Nile virus neuroinvasive disease: neurological manifestations and prospective longitudinal outcomes SO BMC INFECTIOUS DISEASES LA English DT Article DE West Nile virus; Encephalitis; Neurological deficit; 3MS; Coma ID ACUTE FLACCID PARALYSIS; MR-IMAGING FINDINGS; UNITED-STATES; NEW-YORK; INFECTION; EPIDEMIC; MENINGOENCEPHALITIS; ENCEPHALITIS; PROGNOSIS; MOTOR AB Background: West Nile Virus (WNV) is a mosquito-borne flavivirus that has caused ongoing seasonal epidemics in the United States since 1999. It is estimated that = 1% of WNV-infected patients will develop neuroinvasive disease (West Nile encephalitis and/or myelitis) that can result in debilitating morbidities and long-term sequelae. It is essential to collect longitudinal information about the recovery process and to characterize predicative factors that may assist in therapeutic decision-making in the future. Methods: We report a longitudinal study of the neurological outcomes (as measured by neurological examination, Glascow Coma Scale, and Modified Mini-Mental State Examination) for 55 subjects with WNV neuroinvasive disease (confirmed by positive CSF IgM) assessed on day 7, at discharge, and on days 14, 30, and 90. The neurological outcome measures were coma (presence and degree), global cognitive status, presence of cranial neuropathy, tremors and/or weakness. Results: At initial clinical presentation 93% presented with a significant neurological deficit (49% with weakness, 35% with tremor, and 16% with cranial neuropathy). The number of patients with a cognitive deficit fell from 25 at initial evaluation to 9 at their last evaluation. Cranial neuropathy was present in 9 at onset and in only 4 patients at study conclusion. Of the 19 patients who had a tremor at enrollment, 11 continued to exhibit a tremor at follow-up. Seven patients died after initial enrollment in the study, with 5 of those having presented in a coma. The factors that predict either severity or long-term recovery of neurological function include age (older individuals were weaker at follow-up examination), gender (males recovered better from coma), and presentation in a coma with cranial nerve deficits (had a poorer recovery particularly with regard to cognition). Conclusions: This study represents one of the largest clinical investigations providing prospectively-acquired neurological outcomes data among American patients with WNV central nervous system disease. The findings show that the factors that influence prognosis from the initial presentation include age, gender, and specific neurological deficits at onset. C1 [Hart, John, Jr.; Tillman, Gail; Chiang, Hsueh-Sheng; Strain, Jeremy F.] Univ Texas Dallas, Ctr BrainHlth, Dallas, TX 75230 USA. [Kraut, Michael A.] Johns Hopkins Univ, Sch Med, Baltimore, MD USA. [Agrawal, Amy G.] NIH, Bethesda, MD 20892 USA. [Gnann, John W., Jr.] Med Univ S Carolina, Charleston, SC 29425 USA. [Li, Yufeng; Jester, Penny; Whitley, Richard J.] Univ Alabama Birmingham, Birmingham, AL USA. RP Hart, J (reprint author), Univ Texas Dallas, Ctr BrainHlth, Dallas, TX 75230 USA. EM jhart@utdallas.edu FU National Institute of Allergy and Infectious Diseases, National Institutes of Health, Dept. of Health and Human Services [N01-AI-30025] FX This project has been funded in whole or in part with Federal funds from the National Institute of Allergy and Infectious Diseases, National Institutes of Health, Dept. of Health and Human Services, under contract No. N01-AI-30025. NR 31 TC 12 Z9 13 U1 3 U2 15 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1471-2334 J9 BMC INFECT DIS JI BMC Infect. Dis. PD MAY 9 PY 2014 VL 14 AR 248 DI 10.1186/1471-2334-14-248 PG 10 WC Infectious Diseases SC Infectious Diseases GA AH4CF UT WOS:000336072600002 PM 24884681 ER PT J AU Novgorodov, SA Riley, CL Yu, J Borg, KT Hannun, YA Proia, RL Kindy, MS Gudz, TI AF Novgorodov, Sergei A. Riley, Christopher L. Yu, Jin Borg, Keith T. Hannun, Yusuf A. Proia, Richard L. Kindy, Mark S. Gudz, Tatyana I. TI Essential Roles of Neutral Ceramidase and Sphingosine in Mitochondrial Dysfunction Due to Traumatic Brain Injury SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article DE Brain; Cell Death; Mitochondria; Respiratory Chain; Sphingolipid ID CYTOCHROME-C-OXIDASE; SUBCELLULAR-LOCALIZATION; CHRONIC ACTIVATION; RESPIRATORY-CHAIN; MOLECULAR-CLONING; RAT-BRAIN; IN-VITRO; KINASE; SPHINGOSINE-1-PHOSPHATE; SPHINGOLIPIDS AB Background: A cardinal feature of many neurological disorders is mitochondrial dysfunction. Results: Knocking down neutral ceramidase reduces mitochondrial sphingosine, preserves mitochondrial function, and improves brain function recovery after trauma. Conclusion: Activation of the sphingosine-generating pathway plays a significant role in promoting mitochondrial injury. Significance: This is the first direct evidence of endogenous sphingosine involvement in regulation of mitochondrial function. In addition to immediate brain damage, traumatic brain injury (TBI) initiates a cascade of pathophysiological events producing secondary injury. The biochemical and cellular mechanisms that comprise secondary injury are not entirely understood. Herein, we report a substantial deregulation of cerebral sphingolipid metabolism in a mouse model of TBI. Sphingolipid profile analysis demonstrated increases in sphingomyelin species and sphingosine concurrently with up-regulation of intermediates of de novo sphingolipid biosynthesis in the brain. Investigation of intracellular sites of sphingosine accumulation revealed an elevation of sphingosine in mitochondria due to the activation of neutral ceramidase (NCDase) and the reduced activity of sphingosine kinase 2 (SphK2). The lack of change in gene expression suggested that post-translational mechanisms are responsible for the shift in the activities of both enzymes. Immunoprecipitation studies revealed that SphK2 is complexed with NCDase and cytochrome oxidase (COX) subunit 1 in mitochondria and that brain injury hindered SphK2 association with the complex. Functional studies showed that sphingosine accumulation resulted in a decreased activity of COX, a rate-limiting enzyme of the mitochondrial electron transport chain. Knocking down NCDase reduced sphingosine accumulation in mitochondria and preserved COX activity after the brain injury. Also, NCDase knockdown improved brain function recovery and lessened brain contusion volume after trauma. These studies highlight a novel mechanism of secondary TBI involving a disturbance of sphingolipid-metabolizing enzymes in mitochondria and suggest a critical role for mitochondrial sphingosine in promoting brain injury after trauma. C1 [Riley, Christopher L.] Ralph H Johnson Vet Affairs Med Ctr, Charleston, SC 29401 USA. [Yu, Jin; Kindy, Mark S.; Gudz, Tatyana I.] Med Univ S Carolina, Dept Neurosci, Charleston, SC 29425 USA. [Novgorodov, Sergei A.; Kindy, Mark S.; Gudz, Tatyana I.] Med Univ S Carolina, Dept Med, Charleston, SC 29425 USA. [Borg, Keith T.] Med Univ S Carolina, Dept Emergency Med, Charleston, SC 29425 USA. [Hannun, Yusuf A.] Med Univ S Carolina, Dept Biochem & Mol Biol, Charleston, SC 29425 USA. [Proia, Richard L.] NIDDK, Genet Dev & Dis Branch, NIH, Bethesda, MD 20892 USA. RP Gudz, TI (reprint author), 114 Doughty St, Charleston, SC 29425 USA. EM gudz@musc.edu FU National Institutes of Health [P30 GM103339]; Veterans Affairs Merit Awards [I01RX000206, I01BX001104, I01RX000331]; American Diabetes Association [7-12-IN-28] FX This work was supported, in whole or in part, by National Institutes of Health Grant P30 GM103339 (to S. A. N.). This work was also supported by Veterans Affairs Merit Awards I01RX000206 (to T. I. G.), I01BX001104 (to T. I. G.), and I01RX000331 (to M. S. K.). The Lipidomics Core Facility at Medical University of South Carolina is supported in part by National Institutes of Health Grant P30 GM103339.; Supported in part by American Diabetes Association Innovation Grant 7-12-IN-28. NR 64 TC 10 Z9 10 U1 2 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 MAY 9 PY 2014 VL 289 IS 19 BP 13142 EP 13154 DI 10.1074/jbc.M113.530311 PG 13 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA AG6IR UT WOS:000335522800016 PM 24659784 ER PT J AU Liu, CH Sheng, JZ Krahn, JM Perera, L Xu, YM Hsieh, PH Dou, WF Liu, J Pedersen, LC AF Liu, Chunhui Sheng, Juzheng Krahn, Juno M. Perera, Lalith Xu, Yongmei Hsieh, Po-Hung Dou, Wenfang Liu, Jian Pedersen, Lars C. TI Molecular Mechanism of Substrate Specificity for Heparan Sulfate 2-O-Sulfotransferase SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article DE Heparan Sulfate; Heparin; Heparin-binding Protein; Oligosaccharide; Sulfotransferase ID BIOSYNTHESIS; 3-O-SULFOTRANSFERASE; OLIGOSACCHARIDES; PROTEOGLYCANS; C-5-EPIMERASE; DIVERSITY; SYSTEM; MODE; MICE AB Background: Sulfotransferases with distinct specificities act in sequence in the heparan sulfate biosynthetic pathway. Results: The crystal structure of 2-O-sulfotransferase with bound substrate reveals its requirements for substrate recognition. Conclusion: The 2-O-sulfotransferase recognizes N-sulfate but excludes 6-O-sulfate on substrates. Significance: The results advance the understanding of cellular control for the biosynthesis of heparan sulfate. Heparan sulfate (HS) is an abundant polysaccharide in the animal kingdom with essential physiological functions. HS is composed of sulfated saccharides that are biosynthesized through a complex pathway involving multiple enzymes. In vivo regulation of this process remains unclear. HS 2-O-sulfotransferase (2OST) is a key enzyme in this pathway. Here, we report the crystal structure of the ternary complex of 2OST, 3-phosphoadenosine 5-phosphate, and a heptasaccharide substrate. Utilizing site-directed mutagenesis and specific oligosaccharide substrate sequences, we probed the molecular basis of specificity and 2OST position in the ordered HS biosynthesis pathway. These studies revealed that Arg-80, Lys-350, and Arg-190 of 2OST interact with the N-sulfo groups near the modification site, consistent with the dependence of 2OST on N-sulfation. In contrast, 6-O-sulfo groups on HS are likely excluded by steric and electrostatic repulsion within the active site supporting the hypothesis that 2-O-sulfation occurs prior to 6-O-sulfation. Our results provide the structural evidence for understanding the sequence of enzymatic events in this pathway. C1 [Liu, Chunhui; Sheng, Juzheng; Xu, Yongmei; Hsieh, Po-Hung; Dou, Wenfang; Liu, Jian] Univ N Carolina, Eshelman Sch Pharm, Div Chem Biol & Med Chem, Chapel Hill, NC 27599 USA. [Liu, Chunhui; Sheng, Juzheng] Shandong Univ, Sch Pharmaceut Sci, Inst Biochem & Biotechnol Drug, Jinan 250012, Peoples R China. [Krahn, Juno M.; Perera, Lalith; Pedersen, Lars C.] NIEHS, Struct Biol Lab, NIH, Res Triangle Pk, NC 27709 USA. [Dou, Wenfang] Jiangnan Univ, Sch Pharmaceut Sci, Lab Pharmaceut Engn, Wuxi 214122, Peoples R China. RP Liu, J (reprint author), Univ N Carolina, Rm 303,Beard Hall, Chapel Hill, NC 27599 USA. EM jian_liu@unc.edu FU National Institutes of Health [GM102137, HL094463]; National Institutes of Health, NIEHS [ZIAES102645, ZICES043010-28]; China Scholarship Council FX This work was supported, in whole or in part, by National Institutes of Health Grants GM102137 and HL094463 and by the Intramural Research Program of the National Institutes of Health, NIEHS Project ZIAES102645 and ZICES043010-28 (to L. C. P.).; Supported by the China Scholarship Council. NR 38 TC 14 Z9 15 U1 3 U2 31 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 MAY 9 PY 2014 VL 289 IS 19 BP 13407 EP 13418 DI 10.1074/jbc.M113.530535 PG 12 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA AG6IR UT WOS:000335522800039 PM 24652287 ER PT J AU Shi, S Leites, C He, DL Schwartz, D Moy, W Shi, JX Duan, JB AF Shi, Sandra Leites, Catherine He, Deli Schwartz, Daniel Moy, Winton Shi, Jianxin Duan, Jubao TI MicroRNA-9 and MicroRNA-326 Regulate Human Dopamine D2 Receptor Expression, and the MicroRNA-mediated Expression Regulation Is Altered by a Genetic Variant SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article DE Dopamine Receptors; Gene Expression; Gene Regulation; Genetic Polymorphism; MicroRNA; Pharmacogenetics; DRD2 ID C957T POLYMORPHISM; PREFRONTAL CORTEX; MESSENGER-RNA; NT2 CELLS; DRD2 GENE; EXPERIMENTAL VALIDATION; ASSOCIATION ANALYSIS; ANTIPSYCHOTIC-DRUGS; WORKING-MEMORY; SCHIZOPHRENIA AB Background: Regulation of dopamine D2 receptor (DRD2) is pathophysiologically and pharmacologically important. Results: miR-9 and miR-326 target to the 3-UTR of DRD2, and endogenously inhibit DRD2 expression. A functional single nucleotide polymorphism alters such regulation. Conclusion:DRD2 is post-transcriptionally regulated by miR-326 and miR-9. Significance: The study suggests a pathophysiological and pharmacological role of miR-9 and miR-326 in neuropsychiatric disorders. The human dopamine receptor D2 (DRD2) has been implicated in the pathophysiology of schizophrenia and other neuropsychiatric disorders. Most antipsychotic drugs influence dopaminergic transmission through blocking dopamine receptors, primarily DRD2. We report here the post-transcriptional regulation of DRD2 expression by two brain-expressed microRNAs (miRs), miR-326 and miR-9, in an ex vivo mode, and show the relevance of miR-mediated DRD2 expression regulation in human dopaminergic neurons and in developing human brains. Both miRs targeted the 3-UTR (untranslated region) of DRD2 in NT2 (neuron-committed teratocarcinoma, which endogenously expresses DRD2) and CHO (Chinese hamster ovary) cell lines, decreasing luciferase activity measured by a luciferase reporter gene assay. miR-326 overexpression reduced DRD2 mRNA and DRD2 receptor synthesis. Both antisense miR-326 and antisense miR-9 increased DRD2 protein abundance, suggesting an endogenous repression of DRD2 expression by both miRs. Furthermore, a genetic variant (rs1130354) within the DRD2 3-UTR miR-targeting site interferes with miR-326-mediated repression of DRD2 expression. Finally, co-expression analysis identified an inverse correlation of DRD2 expression with both miR-326 and miR-9 in differentiating dopaminergic neurons derived from human induced pluripotent stem cells (iPSCs) and in developing human brain regions implicated in schizophrenia. Our study provides empirical evidence suggesting that miR-326 and miR-9 may regulate dopaminergic signaling, and miR-326 and miR-9 may be considered as potential drug targets for the treatment of disorders involving abnormal DRD2 function, such as schizophrenia. C1 [Shi, Sandra; Leites, Catherine; He, Deli; Schwartz, Daniel; Moy, Winton; Duan, Jubao] NorthShore Univ HealthSyst, Dept Psychiat & Behav Sci, Evanston, IL 60201 USA. [Shi, Sandra; Duan, Jubao] Univ Chicago, Dept Psychiat & Behav Sci, Chicago, IL 60637 USA. [Shi, Jianxin] NCI, Biostat Branch, Div Canc Epidemiol & Genet, NIH, Bethesda, MD 20892 USA. RP Duan, JB (reprint author), NorthShore Univ HealthSyst, Res Inst, 1001 Univ Pl, Evanston, IL 60201 USA. EM jduan@uchicago.edu FU National Institutes of Health [R21MH102685]; Brain and Behavior Research Foundation Young Investigator Award; NorthShore University HealthSystem Research Career Development Award; NorthShore University HealthSystem Pilot Award FX This work was supported, in whole or in part, by National Institutes of Health Grant R21MH102685 (to J.D.). This work was also supported by a Brain and Behavior Research Foundation (formerly NARSAD) Young Investigator Award, NorthShore University HealthSystem Research Career Development Award, and the NorthShore University HealthSystem 2011 Pilot Award (all to J.D.). NR 83 TC 19 Z9 20 U1 0 U2 6 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 MAY 9 PY 2014 VL 289 IS 19 BP 13434 EP 13444 DI 10.1074/jbc.M113.535203 PG 11 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA AG6IR UT WOS:000335522800041 PM 24675081 ER PT J AU Lin, XY Ruiz, J Bajraktari, I Ohman, R Banerjee, S Gribble, K Kaufman, JD Wingfield, PT Griggs, RC Fischbeck, KH Mankodi, A AF Lin, Xiaoyan Ruiz, Janelle Bajraktari, Ilda Ohman, Rachel Banerjee, Soojay Gribble, Katherine Kaufman, Joshua D. Wingfield, Paul T. Griggs, Robert C. Fischbeck, Kenneth H. Mankodi, Ami TI Z-disc-associated, Alternatively Spliced, PDZ Motif-containing Protein ( ZASP) Mutations in the Actin-binding Domain Cause Disruption of Skeletal Muscle Actin Filaments in Myofibrillar Myopathy SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article DE Actin; Muscular Dystrophy; Protein Complex; Protein-Protein Interaction; Skeletal Muscle; Actinin; Myofibrillar Myopathy; Myotilin; Z-disc; ZASP ID GIRDLE MUSCULAR-DYSTROPHY; ONSET DISTAL MYOPATHY; ALPHA-ACTININ; DILATED CARDIOMYOPATHY; LIM PROTEIN; Z-BAND; DESMIN POSITIVITY; SEVERE FORM; IN-VIVO; Z-LINE AB Background: The binding partners of the ZASP internal region that is mutated in zaspopathy are not yet known. Results: The internal region of ZASP binds to skeletal muscle -actin, and zaspopathy mutations cause actin disruption. Conclusion: ZASP mutations in the actin-binding domain are deleterious to the muscle Z-disc structure. Significance: ZASP-actin interaction expands the role of ZASP and defines the mechanism of zaspopathy. The core of skeletal muscle Z-discs consists of actin filaments from adjacent sarcomeres that are cross-linked by -actinin homodimers. Z-disc-associated, alternatively spliced, PDZ motif-containing protein (ZASP)/Cypher interacts with -actinin, myotilin, and other Z-disc proteins via the PDZ domain. However, these interactions are not sufficient to maintain the Z-disc structure. We show that ZASP directly interacts with skeletal actin filaments. The actin-binding domain is between the modular PDZ and LIM domains. This ZASP region is alternatively spliced so that each isoform has unique actin-binding domains. All ZASP isoforms contain the exon 6-encoded ZASP-like motif that is mutated in zaspopathy, a myofibrillar myopathy (MFM), whereas the exon 8-11 junction-encoded peptide is exclusive to the postnatal long ZASP isoform (ZASP-Lex10). MFM is characterized by disruption of skeletal muscle Z-discs and accumulation of myofibrillar degradation products. Wild-type and mutant ZASP interact with -actin, -actinin, and myotilin. Expression of mutant, but not wild-type, ZASP leads to Z-disc disruption and F-actin accumulation in mouse skeletal muscle, as in MFM. Mutations in the actin-binding domain of ZASP-Lex10, but not other isoforms, cause disruption of the actin cytoskeleton in muscle cells. These isoform-specific mutation effects highlight the essential role of the ZASP-Lex10 isoform in F-actin organization. Our results show that MFM-associated ZASP mutations in the actin-binding domain have deleterious effects on the core structure of the Z-discs in skeletal muscle. C1 [Lin, Xiaoyan; Ruiz, Janelle; Bajraktari, Ilda; Ohman, Rachel; Banerjee, Soojay; Gribble, Katherine; Fischbeck, Kenneth H.; Mankodi, Ami] NINDS, NIH, Neurogenet Branch, Bethesda, MD 20892 USA. [Kaufman, Joshua D.; Wingfield, Paul T.] NIAMS, NIH, Prot Express Lab, Bethesda, MD 20892 USA. [Griggs, Robert C.] Univ Rochester, Med Ctr, Dept Neurol, Rochester, NY 14642 USA. RP Mankodi, A (reprint author), NINDS, NIH, Neurogenet Branch, 35 Convent Dr,Bldg 35,Rm 2A-1002, Bethesda, MD 20892 USA. EM ami.mankodi@nih.gov FU NINDS, National Institute of Health FX This work was supported by NINDS, National Institute of Health intramural research funds, including the Henry F. McFarland Transition to Independence Award (to A. M.). NR 41 TC 9 Z9 9 U1 0 U2 5 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 EI 1083-351X J9 J BIOL CHEM JI J. Biol. Chem. PD MAY 9 PY 2014 VL 289 IS 19 BP 13615 EP 13626 DI 10.1074/jbc.M114.550418 PG 12 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA AG6IR UT WOS:000335522800055 PM 24668811 ER PT J AU Ma, XJ Espana-Serrano, L Kim, WJ Purayil, HT Nie, ZZ Daaka, Y AF Ma, Xiaojie Espana-Serrano, Laura Kim, Wan-ju Purayil, Hamsa Thayele Nie, Zhongzhen Daaka, Yehia TI beta Arrestin1 Regulates the Guanine Nucleotide Exchange Factor RasGRF2 Expression and the Small GTPase Rac- mediated Formation of Membrane Protrusion and Cell Motility SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article DE Actin; Arrestin; Cell Migration; G Protein-coupled Receptors (GPCR); Guanine Nucleotide Exchange Factor (GEF); Rac; Protrusion ID PROTEASE-ACTIVATED RECEPTOR-2; COFILIN PHOSPHORYLATION; CYTOSKELETAL DYNAMICS; SIGNAL-TRANSDUCTION; BETA-ARRESTINS; LIM-KINASE; IDENTIFICATION; DOWNSTREAM; MIGRATION; PATHWAY AB Background: G protein-coupled receptors (GPCRs) and arrestins have been shown to regulate cell motility. Results: Arrestin1 regulates cell migration through RasGRF2 (a dual guanine nucleotide exchange factor) gene expression and the small GTPase Rac activity. Conclusion: Arrestin1 may regulate cellular functions at the gene expression level. Significance: Arrestins may function at transcriptional and post-translational levels to regulate cell migration. Arrestin proteins shuttle between the cytosol and nucleus and have been shown to regulate G protein-coupled receptor signaling, actin remodeling, and gene expression. Here, we tested the hypothesis that arrestin1 regulates actin remodeling and cell migration through the small GTPase Rac. Depletion of arrestin1 promotes Rac activation, leading to the formation of multipolar protrusions and increased cell circularity, and overexpression of a dominant negative form of Rac reverses these morphological changes. Small interfering RNA library screen identifies RasGRF2 as a target of arrestin1. RasGRF2 gene and protein expression levels are elevated following depletion of arrestin1, and the consequent activation of Rac results in dephosphorylation of cofilin that can promote actin polymerization and formation of multipolar protrusions, thereby retarding cell migration and invasion. Together, these results suggest that arrestin1 regulates rasgrf2 gene expression and Rac activation to affect membrane protrusion and cell migration and invasion. C1 [Ma, Xiaojie; Espana-Serrano, Laura; Kim, Wan-ju; Purayil, Hamsa Thayele; Nie, Zhongzhen; Daaka, Yehia] Univ Florida, Coll Med, Dept Anat & Cell Biol, Gainesville, FL 32610 USA. RP Nie, ZZ (reprint author), NIGMS, NIH, Div Cell Biol & Biophys, 45 Ctr Dr,Rm 2AS13H,MSC6200, Bethesda, MD 20892 USA. EM niezhong@nigms.nih.gov RI THAYELE PURAYIL, HAMSA/E-7533-2015 FU National Institutes of Health from USPHS [K22CA124578]; NCI [R01CA129155] FX This work was supported, in whole or in part, by National Institutes of Health Grants K22CA124578 from USPHS (to Z. N.) and R01CA129155 from NCI (to Y. D.). NR 44 TC 4 Z9 4 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 MAY 9 PY 2014 VL 289 IS 19 BP 13638 EP 13650 DI 10.1074/jbc.M113.511360 PG 13 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA AG6IR UT WOS:000335522800057 PM 24692549 ER PT J AU DuPont, RL Lieberman, JA AF DuPont, Robert L. Lieberman, Jeffrey A. TI Young Brains on Drugs SO SCIENCE LA English DT Editorial Material C1 [DuPont, Robert L.] US Natl Inst Drug Abuse, Bethesda, MD USA. [DuPont, Robert L.] Inst Behav & Hlth Inc, Rockville, MD 20852 USA. [Lieberman, Jeffrey A.] Amer Psychiat Assoc, Washington, DC 20005 USA. [Lieberman, Jeffrey A.] Columbia Univ, Dept Psychiat, New York, NY USA. RP DuPont, RL (reprint author), Inst Behav & Hlth Inc, Rockville, MD 20852 USA. EM jlieberman@columbia.edu NR 0 TC 5 Z9 5 U1 0 U2 17 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 MAY 9 PY 2014 VL 344 IS 6184 BP 557 EP 557 PG 1 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA AG6OD UT WOS:000335537400001 PM 24812368 ER PT J AU Mindell, JA AF Mindell, Joseph A. TI A SWELL Channel Indeed SO SCIENCE LA English DT Editorial Material C1 NINDS, Membrane Transport Biophys Sect, Porter Neurosci Res Ctr, NIH, Bethesda, MD 20892 USA. RP Mindell, JA (reprint author), NINDS, Membrane Transport Biophys Sect, Porter Neurosci Res Ctr, NIH, Bethesda, MD 20892 USA. EM mindellj@ninds.nih.gov OI Mindell, Joseph/0000-0002-6952-8247 NR 4 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 MAY 9 PY 2014 VL 344 IS 6184 BP 585 EP 586 DI 10.1126/science.1254591 PG 2 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA AG6OD UT WOS:000335537400026 PM 24812387 ER PT J AU Tran, E Turcotte, S Gros, A Robbins, PF Lu, YC Dudley, ME Wunderlich, JR Somerville, RP Hogan, K Hinrichs, CS Parkhurst, MR Yang, JC Rosenberg, SA AF Tran, Eric Turcotte, Simon Gros, Alena Robbins, Paul F. Lu, Yong-Chen Dudley, Mark E. Wunderlich, John R. Somerville, Robert P. Hogan, Katherine Hinrichs, Christian S. Parkhurst, Maria R. Yang, James C. Rosenberg, Steven A. TI Cancer Immunotherapy Based on Mutation-Specific CD4+T Cells in a Patient with Epithelial Cancer SO SCIENCE LA English DT Article ID CD4(+) T-CELLS; METASTATIC MELANOMA; ESTABLISHED MELANOMA; TUMOR-REGRESSION; LUNG-CARCINOMA; IFN-GAMMA; IN-VIVO; LYMPHOCYTES; GENE; RESPONSES AB Limited evidence exists that humans mount a mutation-specific T cell response to epithelial cancers. We used a whole-exomic-sequencing-based approach to demonstrate that tumor-infiltrating lymphocytes (TIL) from a patient with metastatic cholangiocarcinoma contained CD4+ T helper 1 (T(H)1) cells recognizing a mutation in erbb2 interacting protein (ERBB2IP) expressed by the cancer. After adoptive transfer of TIL containing about 25% mutation-specific polyfunctional T(H)1 cells, the patient achieved a decrease in target lesions with prolonged stabilization of disease. Upon disease progression, the patient was retreated with a >95% pure population of mutation-reactive T(H)1 cells and again experienced tumor regression. These results provide evidence that a CD4+ T cell response against a mutated antigen can be harnessed to mediate regression of a metastatic epithelial cancer. C1 [Tran, Eric; Turcotte, Simon; Gros, Alena; Robbins, Paul F.; Lu, Yong-Chen; Dudley, Mark E.; Wunderlich, John R.; Somerville, Robert P.; Hogan, Katherine; Hinrichs, Christian S.; Parkhurst, Maria R.; Yang, James C.; Rosenberg, Steven A.] NCI, Surg Branch, NIH, Bethesda, MD 20892 USA. RP Rosenberg, SA (reprint author), NCI, Surg Branch, NIH, Bldg 10, Bethesda, MD 20892 USA. EM sar@nih.gov RI Lu, Yong-Chen/G-4520-2014; OI Lu, Yong-Chen/0000-0002-0275-9825; Gros, Alena/0000-0002-1207-1880 FU Intramural Research Program of the NIH; NCI; [PRJNA243084] FX We thank the Milstein Family Foundation for their generous support; C.-C. R. Lee, Y. F. Li, A. Mixon, S. Farid, and J. Gartner for helpful technical support and reagents; and the Surgery Branch clinical team for outstanding patient care. The data presented in this manuscript are tabulated in the main paper and the supplementary materials. The raw whole-exome sequence data are available on the Sequence Read Archive database: Bioproject PRJNA243084. This research was supported by the Intramural Research Program of the NIH and NCI. NR 25 TC 320 Z9 327 U1 7 U2 110 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 MAY 9 PY 2014 VL 344 IS 6184 BP 641 EP 645 DI 10.1126/science.1251102 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA AG6OD UT WOS:000335537400046 PM 24812403 ER PT J AU Mayse, JD Nelson, GM Park, P Gallagher, M Lin, SC AF Mayse, Jeffrey D. Nelson, Geoffrey M. Park, Pul Gallagher, Michela Lin, Shih-Chieh TI Proactive and reactive inhibitory control in rats SO FRONTIERS IN NEUROSCIENCE LA English DT Article DE stop signal; stop signal reaction time; reactive; proactive; inhibitory control; impulsivity; executive function; decision making ID REACTION-TIME-TASK; STOP-SIGNAL TASK; RESPONSE-INHIBITION; IMPULSIVE CHOICE; PERFORMANCE; LESIONS; MODEL; ATTENTION; PARADIGM; CORTEX AB Inhibiting actions inappropriate for the behavioral context, or inhibitory control, is essential for survival and involves both reactively stopping the current prepared action and proactively adjusting behavioral tendencies to increase future performance. A powerful paradigm widely used in basic and clinical research to study inhibitory control is the stop signal task (SST). Recent years have seen a surging interest in translating the SST to rodents to study the neural mechanisms underlying inhibitory control. However, significant differences in task designs and behavioral strategies between rodent and primate studies have made it difficult to directly compare the two literatures. In this study, we developed a rodent-appropriate SST and characterized both reactive and proactive control in rats. For reactive inhibitory control, we found that, unlike in primates, incorrect stop trials in rodents result from two independent types of errors: an initial failure-to-stop error or, after successful stopping, a subsequent failure-to-wait error. Conflating failure-to-stop and failure-to-wait errors systematically overestimates the covert latency of reactive inhibition, the stop signal reaction time (SSRT). To correctly estimate SSRT, we developed and validated a new method that provides an unbiased SSRT estimate independent of the ability to wait. For proactive inhibitory control, we found that rodents adjust both their reaction time and the ability to stop following failure-to-wait errors and successful stop trials, but not after failure-to-stop errors. Together, these results establish a valid rodent model that utilizes proactive and reactive inhibitory control strategies similar to primates, and highlight the importance of dissociating initial stopping from subsequent waiting in studying mechanisms of inhibitory control using rodents. C1 [Mayse, Jeffrey D.; Gallagher, Michela] Johns Hopkins Univ, Dept Psychol & Brain Sci, Baltimore, MD USA. [Mayse, Jeffrey D.; Nelson, Geoffrey M.; Lin, Shih-Chieh] NIA, Neural Circuits & Cognit Unit, Lab Behav Neurosci, NIH, Baltimore, MD 21224 USA. [Park, Pul] NIA, Neurocognit Aging Sect, 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 Nelson, Geoffrey/0000-0001-9825-4241; Lin, Shih-Chieh/0000-0003-3693-5476 FU Intramural Research Program of the National Institute on Aging, NIH, USA; National Institute on Aging [AG045039-01A1] FX We thank P. R. Rapp, P. C. Holland, N. W. Simon, and Z. Xu for critical discussions and reading of the manuscript. This research is funded by the Intramural Research Program of the National Institute on Aging, NIH, USA and the National Institute on Aging grant AG045039-01A1. NR 51 TC 5 Z9 5 U1 2 U2 2 PU FRONTIERS RESEARCH FOUNDATION PI LAUSANNE PA PO BOX 110, LAUSANNE, 1015, SWITZERLAND SN 1662-453X J9 FRONT NEUROSCI-SWITZ JI Front. Neurosci. PD MAY 8 PY 2014 VL 8 AR 104 DI 10.3389/fnins.2014.00104 PG 16 WC Neurosciences SC Neurosciences & Neurology GA AW7YM UT WOS:000346477600001 PM 24847204 ER PT J AU Chen, MM Crous-Bou, M Setiawan, VW Prescott, J Olson, SH Wentzensen, N Black, A Brinton, L Chen, C Chen, C Cook, LS Doherty, J Friedenreich, CM Hankinson, SE Hartge, P Henderson, BE Hunter, DJ Le Marchand, L Liang, XL Lissowska, J Lu, LG Orlow, I Petruzella, S Polidoro, S Pooler, L Rebbeck, TR Risch, H Sacerdote, C Schumacher, F Sheng, X Shu, XO Weiss, NS Xia, L Van den Berg, D Yang, HP Yu, H Chanock, S Haiman, C Kraft, P De Vivo, I AF Chen, Maxine M. Crous-Bou, Marta Setiawan, Veronica W. Prescott, Jennifer Olson, Sara H. Wentzensen, Nicolas Black, Amanda Brinton, Louise Chen, Chu Chen, Constance Cook, Linda S. Doherty, Jennifer Friedenreich, Christine M. Hankinson, Susan E. Hartge, Patricia Henderson, Brian E. Hunter, David J. Le Marchand, Loic Liang, Xiaolin Lissowska, Jolanta Lu, Lingeng Orlow, Irene Petruzella, Stacey Polidoro, Silvia Pooler, Loreall Rebbeck, Timothy R. Risch, Harvey Sacerdote, Carlotta Schumacher, Frederick Sheng, Xin Shu, Xiao-ou Weiss, Noel S. Xia, Lucy Van den Berg, David Yang, Hannah P. Yu, Herbert Chanock, Stephen Haiman, Christopher Kraft, Peter De Vivo, Immaculata TI Exome-Wide Association Study of Endometrial Cancer in a Multiethnic Population SO PLOS ONE LA English DT Article ID PROTEIN-S; GENE-EXPRESSION; PROSTATE-CANCER; RISK; SUSCEPTIBILITY; METAANALYSIS; VARIANTS; OBESITY AB Endometrial cancer (EC) contributes substantially to total burden of cancer morbidity and mortality in the United States. Family history is a known risk factor for EC, thus genetic factors may play a role in EC pathogenesis. Three previous genome-wide association studies (GWAS) have found only one locus associated with EC, suggesting that common variants with large effects may not contribute greatly to EC risk. Alternatively, we hypothesize that rare variants may contribute to EC risk. We conducted an exome-wide association study (EXWAS) of EC using the Infinium HumanExome BeadChip in order to identify rare variants associated with EC risk. We successfully genotyped 177,139 variants in a multiethnic population of 1,055 cases and 1,778 controls from four studies that were part of the Epidemiology of Endometrial Cancer Consortium (E2C2). No variants reached global significance in the study, suggesting that more power is needed to detect modest associations between rare genetic variants and risk of EC. C1 [Chen, Maxine M.; Crous-Bou, Marta; Chen, Constance; Hunter, David J.; Kraft, Peter; De Vivo, Immaculata] Harvard Univ, Sch Publ Hlth, Program Genet Epidemiol & Stat Genet, Boston, MA 02115 USA. [Crous-Bou, Marta; Prescott, Jennifer; Hankinson, Susan E.; De Vivo, Immaculata] Brigham & Womens Hosp, Dept Med, Channing Div Network Med, Boston, MA 02115 USA. [Crous-Bou, Marta; Prescott, Jennifer; Hankinson, Susan E.; De Vivo, Immaculata] Harvard Univ, Sch Med, Boston, MA 02115 USA. [Setiawan, Veronica W.; Henderson, Brian E.; Pooler, Loreall; Sheng, Xin; Xia, Lucy; Van den Berg, David; Haiman, Christopher] Univ So Calif, Los Angeles, CA USA. [Olson, Sara H.; Liang, Xiaolin; Orlow, Irene; Petruzella, Stacey] Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. [Wentzensen, Nicolas; Black, Amanda; Brinton, Louise; Yang, Hannah P.; Chanock, Stephen] NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. [Chen, Chu] Fred Hutchinson Canc Res Ctr, Seattle, WA 98104 USA. [Cook, Linda S.] Univ New Mexico, Albuquerque, NM 87131 USA. [Cook, Linda S.; Friedenreich, Christine M.] CancerControl Alberta, Alberta Hlth Serv, Calgary, AB, Canada. [Doherty, Jennifer] Dartmouth Coll, Geisel Sch Med, Hanover, NH 03755 USA. [Hankinson, Susan E.] Univ Massachusetts, Dept Biostat & Epidemiol, Amherst, MA 01003 USA. [Le Marchand, Loic] Univ Hawaii, Ctr Canc, Honolulu, HI 96822 USA. [Lissowska, Jolanta] M Sklodowska Curie Canc Ctr, Dept Canc Epidemiol & Prevent, Warsaw, Poland. [Lissowska, Jolanta] Inst Oncol, Warsaw, Poland. [Lu, Lingeng; Risch, Harvey] Yale Univ, Sch Publ Hlth, New Haven, CT USA. [Polidoro, Silvia; Sacerdote, Carlotta] Ctr Canc Prevent CPO Piemonte, Turin, Italy. [Polidoro, Silvia; Sacerdote, Carlotta] Human Genet Fdn HuGeF, Turin, Italy. [Rebbeck, Timothy R.] Univ Penn, Sch Med, Ctr Clin Epidemiol & Biostat, Philadelphia, PA 19104 USA. [Schumacher, Frederick] Canc Prevent Inst Calif, Fremont, CA USA. [Shu, Xiao-ou] Vanderbilt Univ, Med Ctr, Nashville, TN USA. [Weiss, Noel S.] Univ Washington, Seattle, WA 98195 USA. RP De Vivo, I (reprint author), Harvard Univ, Sch Publ Hlth, Program Genet Epidemiol & Stat Genet, 665 Huntington Ave, Boston, MA 02115 USA. EM nhidv@channing.harvard.edu RI Brinton, Louise/G-7486-2015; OI Brinton, Louise/0000-0003-3853-8562; Chen, Maxine/0000-0001-7138-6228; Sacerdote, Carlotta/0000-0002-8008-5096; Orlow, Irene/0000-0001-6234-6961 FU NCI, NIH [1R01 CA134958, 2R01 CA082838, P01 CA087969, R01 CA49449, CA54281, CA128008, R01CA83918, P30-CA008748]; NCI [5T32CA009001-38]; Spanish Ministry of Health, Carlos III Health Institute; NIH [RO1 CA105212, RO1 CA 87538, RO1 CA75977, RO3 CA80636, NO1 HD23166, R35 CA39779, KO5 CA92002]; Fred Hutchinson Cancer Research Center; National Cancer Institute of Canada; Canadian Cancer Society; Canadian Institute for Health Research; Alberta Innovates-Health Solutions; Alberta Cancer Foundation through the Weekend to End Women's Cancers Breast Cancer Chair; Canada Research Chairs program FX The Nurses' Health Study (NHS) investigators are supported by the NCI, NIH Grants Number 1R01 CA134958, 2R01 CA082838, P01 CA087969, and R01 CA49449. MMC is supported by training grant 5T32CA009001-38 from the NCI. MCB is also supported by a Sara Borrell postdoctoral fellowship from the Spanish Ministry of Health, Carlos III Health Institute. The Multiethnic Cohort Study (MEC) is supported by the NCI, NHI Grants Number CA54281, CA128008, and 2R01 CA082838. The Fred Hutchinson Cancer Research Center (FHCRC) is supported by NCI, NIH Grant Number 2R01 CA082838, NIH RO1 CA105212, RO1 CA 87538, RO1 CA75977, RO3 CA80636, NO1 HD23166, R35 CA39779, KO5 CA92002 and funds from the Fred Hutchinson Cancer Research Center. The EDGE Study (Estrogen, Diet, Genetics, and Endometrial Cancer) is supported by NCI, NIH Grants Number 2R01 CA082838, R01CA83918 (Olson PI) and P30-CA008748 (Cancer Center Support Grant). The Alberta Health Services Study (AHS) was supported by operating grants obtained from the National Cancer Institute of Canada with funds from the Canadian Cancer Society and the Canadian Institute for Health Research. The AHS is also supported by NCI, NIH Grant Number 2R01 CA082838. Dr Christine Friedenreich is supported by career awards from Alberta Innovates-Health Solutions and the Alberta Cancer Foundation through the Weekend to End Women's Cancers Breast Cancer Chair. Dr Linda Cook was supported through the Canada Research Chairs program. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 34 TC 4 Z9 4 U1 0 U2 2 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA SN 1932-6203 J9 PLOS ONE JI PLoS One PD MAY 8 PY 2014 VL 9 IS 5 AR e97045 DI 10.1371/journal.pone.0097045 PG 9 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA AK1XT UT WOS:000338213300113 PM 24810602 ER PT J AU Goncalves, BP Huang, CY Morrison, R Holte, S Kabyemela, E Prevots, DR Fried, M Duffy, PE AF Goncalves, Bronner P. Huang, Chiung-Yu Morrison, Robert Holte, Sarah Kabyemela, Edward Prevots, D. Rebecca Fried, Michal Duffy, Patrick E. TI Parasite Burden and Severity of Malaria in Tanzanian Children SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Article ID PLASMODIUM-FALCIPARUM MALARIA; SICKLE-CELL GENE; AFRICAN CHILDREN; RURAL AREA; WEST-AFRICA; MORTALITY; MORBIDITY; TRANSMISSION; IMMUNITY; KENYA AB BackgroundSevere Plasmodium falciparum malaria is a major cause of death in children. The contribution of the parasite burden to the pathogenesis of severe malaria has been controversial. MethodsWe documented P. falciparum infection and disease in Tanzanian children followed from birth for an average of 2 years and for as long as 4 years. ResultsOf the 882 children in our study, 102 had severe malaria, but only 3 had more than two episodes. More than half of first episodes of severe malaria occurred after a second infection. Although parasite levels were higher on average when children had severe rather than mild disease, most children (67 of 102) had high-density infection (>2500 parasites per 200 white cells) with only mild symptoms before severe malaria, after severe malaria, or both. The incidence of severe malaria decreased considerably after infancy, whereas the incidence of high-density infection was similar among all age groups. Infections before and after episodes of severe malaria were associated with similar parasite densities. Nonuse of bed nets, placental malaria at the time of a woman's second or subsequent delivery, high-transmission season, and absence of the sickle cell trait increased severe-malaria risk and parasite density during infections. ConclusionsResistance to severe malaria was not acquired after one or two mild infections. Although the parasite burden was higher on average during episodes of severe malaria, a high parasite burden was often insufficient to cause severe malaria even in children who later were susceptible. The diverging rates of severe disease and high-density infection after infancy, as well as the similar parasite burdens before and after severe malaria, indicate that naturally acquired resistance to severe malaria is not explained by improved control of parasite density. (Funded by the National Institute of Allergy and Infectious Diseases and others.) The pathogenesis of severe malaria due to Plasmodium falciparum remains controversial. In this study conducted over several years and involving 882 Tanzanian children, parasite burden was insufficient to explain the development of severe illness. Although almost 600,000 African children die each year from malaria,(1) most infections in children are mild.(2),(3) Fundamental questions about the pathogenesis of malaria remain unresolved, such as the relative contributions of parasite burden and host inflammation to severe disease.(4) In areas where transmission is stable, severe malaria is unlikely to occur after 5 years of age, presumably as a result of immunity,(5) and mathematical models suggest that protection against noncerebral severe malaria develops after one or two infections.(6) The mechanism of protective immunity is unclear; it might, for example, involve the reduction of parasite density or the blocking of ... C1 [Goncalves, Bronner P.; Fried, Michal; Duffy, Patrick E.] NIAID, Lab Malaria Immunol & Vaccinol, NIH, Rockville, MD 20852 USA. [Goncalves, Bronner P.; Prevots, D. Rebecca] NIAID, Lab Clin Infect Dis, Epidemiol Unit, NIH, Rockville, MD 20852 USA. [Huang, Chiung-Yu] NIAID, Biostat Res Branch, NIH, Rockville, MD 20852 USA. [Morrison, Robert; Fried, Michal; Duffy, Patrick E.] Seattle Biomed Res Inst, Seattle, WA 98109 USA. [Holte, Sarah] Fred Hutchinson Canc Res Ctr, Seattle, WA 98104 USA. [Kabyemela, Edward; Fried, Michal; Duffy, Patrick E.] Muheza Designated Dist Hosp, Offspring Malaria Studies Project, Muheza, Tanzania. RP Duffy, PE (reprint author), NIAID, Lab Malaria Immunol & Vaccinol, NIH, Twinbrook 1,Rm 111,5640 Fishers Lane, Rockville, MD 20852 USA. EM patrick.duffy@nih.gov FU Intramural Research Program of the National Institute of Allergy and Infectious Diseases (NIAID), National Institutes of Health (NIH); NIAID extramural program [R01AI52059]; Fogarty International Center of the NIH [D43 TW005509]; Foundation for the NIH through the Grand Challenges in Global Health Initiative - Bill and Melinda Gates Foundation [1364] FX Supported by the Intramural Research Program of the National Institute of Allergy and Infectious Diseases (NIAID), National Institutes of Health (NIH), and by grants from the NIAID extramural program (R01AI52059), the Fogarty International Center (D43 TW005509) of the NIH, and the Foundation for the NIH through the Grand Challenges in Global Health Initiative, which is funded by the Bill and Melinda Gates Foundation (1364). NR 40 TC 28 Z9 28 U1 0 U2 13 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 MAY 8 PY 2014 VL 370 IS 19 BP 1799 EP 1808 DI 10.1056/NEJMoa1303944 PG 10 WC Medicine, General & Internal SC General & Internal Medicine GA AH3CD UT WOS:000335997900008 PM 24806160 ER PT J AU Battiwalla, M AF Battiwalla, Minoo TI Abnl(17p) in AML: who will guard the guardian? SO BLOOD LA English DT Editorial Material ID ACUTE MYELOID-LEUKEMIA; KARYOTYPE; MUTATIONS; IMPACT AB In this issue of Blood, Middeke and colleagues highlight the poor outcome of the abnormal (17p) [abnl(17p)] subgroup of cytogenetically adverse-risk acute myeloid leukemia (AML) even after allogeneic hematopoietic stem cell transplantation (HSCT).(1) C1 Natl Inst Hlth, Bethesda, MD 20892 USA. RP Battiwalla, M (reprint author), Natl Inst Hlth, Bethesda, MD 20892 USA. NR 10 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 MAY 8 PY 2014 VL 123 IS 19 BP 2906 EP 2907 DI 10.1182/blood-2014-04-565515 PG 2 WC Hematology SC Hematology GA AH1RF UT WOS:000335897900003 PM 24810623 ER PT J AU Iqbal, J Wright, G Wang, C Rosenwald, A Gascoyne, RD Weisenburger, DD Greiner, TC Smith, L Guo, SP Wilcox, RA Teh, B Lim, ST Tan, SY Rimsza, LM Jaffe, ES Campo, E Martinez, A Delabie, J Braziel, RM Cook, JR Tubbs, RR Ott, G Geissinger, E Gaulard, P Piccaluga, PP Pileri, SA Au, WY Nakamura, S Seto, M Berger, F de Leval, L Connors, JM Armitage, J Vose, J Chan, WC Staudt, LM AF Iqbal, Javeed Wright, George Wang, Chao Rosenwald, Andreas Gascoyne, Randy D. Weisenburger, Dennis D. Greiner, Timothy C. Smith, Lynette Guo, Shuangping Wilcox, Ryan A. Teh, Bin Tean Lim, Soon Thye Tan, Soon Yong Rimsza, Lisa M. Jaffe, Elaine S. Campo, Elias Martinez, Antonio Delabie, Jan Braziel, Rita M. Cook, James R. Tubbs, Raymond R. Ott, German Geissinger, Eva Gaulard, Philippe Piccaluga, Pier Paolo Pileri, Stefano A. Au, Wing Y. Nakamura, Shigeo Seto, Masao Berger, Francoise de Leval, Laurence Connors, Joseph M. Armitage, James Vose, Julie Chan, Wing C. Staudt, Louis M. CA Lymphoma Leukemia Mol Profiling Pr Int Peripheral T-cell Lymphoma Pro TI Gene expression signatures delineate biological and prognostic subgroups in peripheral T-cell lymphoma SO BLOOD LA English DT Article ID DENDRITIC CELLS; IDENTIFICATION; DIFFERENTIATION; RECOGNITION; PREDICTION; PROFILES; EFFECTOR; SURVIVAL; FEATURES; SUBTYPES AB Peripheral T-cell lymphoma (PTCL) encompasses a heterogeneous group of neoplasms with generally poor clinical outcome. Currently 50% of PTCL cases are not classifiable: PTCL-not otherwise specified (NOS). Gene-expression profiles on 372 PTCL cases were analyzed and robust molecular classifiers and oncogenic pathways that reflect the pathobiology of tumor cells and their microenvironment were identified for major PTCL-entities, including 114 angioimmunoblastic T-cell lymphoma (AITL), 31 anaplastic lymphoma kinase (ALK)-positive and 48 ALK-negative anaplastic large cell lymphoma, 14 adult T-cell leukemia/lymphoma and 44 extranodal NK/T-cell lymphoma that were further separated into NK-cell and gdT-cell lymphomas. Thirty-seven percent of morphologically diagnosed PTCL-NOS cases were reclassified into other specific subtypes by molecular signatures. Reexamination, immunohistochemistry, and IDH2 mutation analysis in reclassified cases supported the validity of the reclassification. Two major molecular subgroups can be identified in the remaining PTCL-NOS cases characterized by high expression of either GATA3 (33%; 40/121) or TBX21 (49%; 59/121). The GATA3 subgroup was significantly associated with poor overall survival (P = .01). High expression of cytotoxic gene-signature within the TBX21 subgroup also showed poor clinical outcome (P = .05). InAITL, high expression of several signatures associated with the tumor microenvironment was significantly associated with outcome. A combined prognostic score was predictive of survival in an independent cohort (P = .004). C1 [Iqbal, Javeed; Wang, Chao; Greiner, Timothy C.; Guo, Shuangping] Univ Nebraska, Med Ctr, Dept Pathol & Microbiol, Omaha, NE 68198 USA. [Wright, George; Staudt, Louis M.] NCI, Metab Branch, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. [Rosenwald, Andreas; Geissinger, Eva] Univ Wurzburg, Inst Pathol, Wurzburg, Germany. [Gascoyne, Randy D.; Connors, Joseph M.] British Columbia Canc Agcy, Ctr Lymphoid Canc, Vancouver, BC V5Z 4E6, Canada. [Weisenburger, Dennis D.] City Hope Natl Med Ctr, Dept Pathol, Duarte, CA 91010 USA. [Smith, Lynette; Chan, Wing C.] Univ Nebraska Med Ctr, Coll Publ Hlth, Dept Biostat, Omaha, NE USA. [Wilcox, Ryan A.] Univ Michigan, Dept Internal Med, Ctr Comprehens Canc, Ann Arbor, MI 48109 USA. [Teh, Bin Tean; Lim, Soon Thye; Tan, Soon Yong] Natl Canc Ctr, Singapore, Singapore. [Teh, Bin Tean; Lim, Soon Thye; Tan, Soon Yong] Duke Natl Univ Singapore, Grad Sch Med, Singapore, Singapore. [Rimsza, Lisa M.] Univ Arizona, Dept Pathol, Tucson, AZ USA. [Jaffe, Elaine S.] NCI, Pathol Lab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. [Campo, Elias; Martinez, Antonio] Univ Barcelona, Hosp Clin, Inst Invest Bomed August Pi & Sunyer, Barcelona, Spain. [Delabie, Jan] Univ Oslo, Norwegian Radium Hosp, Dept Pathol, Oslo, Norway. [Braziel, Rita M.] Oregon Hlth & Sci Univ, Dept Clin Pathol, Portland, OR 97201 USA. [Cook, James R.; Tubbs, Raymond R.] Cleveland Clin, Dept Mol Pathol & Lab Med, Cleveland, OH 44106 USA. [Ott, German] Robert Bosch Krankenhaus, Dept Clin Pathol, Stuttgart, Germany. [Ott, German] Dr Margarete Fischer Bosch Inst Clin Pharmacol, Stuttgart, Germany. [Gaulard, Philippe] Univ Paris Est, Grp Henri Mondor Albert Chenevier, INSERM, Dept Pathol,U955, Creteil, France. [Piccaluga, Pier Paolo; Pileri, Stefano A.] Univ Bologna, S Orsola Malpighi Hosp, Inst Hematol & Med Oncol L&A Seragnoli, Bologna, Italy. [Au, Wing Y.] Queen Mary Hosp, Hong Kong, Hong Kong, Peoples R China. [Nakamura, Shigeo; Seto, Masao] Aichi Canc Ctr, Nagoya, Aichi 464, Japan. [Berger, Francoise] Ctr Hosp Lyon Sud, Lyon, France. [de Leval, Laurence] CHU Vaudois, Univ Inst Pathol, CH-1011 Lausanne, Switzerland. [Armitage, James; Vose, Julie] Univ Nebraska Med Ctr, Dept Hematol Oncol, Omaha, NE USA. RP Iqbal, J (reprint author), Univ Nebraska, Med Ctr, Dept Pathol & Microbiol, 983135 Nebraska Med Ctr, Omaha, NE 68198 USA. EM jiqbal@unmc.edu; jochan@coh.org; lstaudt@mail.nih.gov RI Nakamura, Shigeo/I-1571-2012; Campo, elias/O-7192-2016; OI Campo, elias/0000-0001-9850-9793; Delabie, Jan/0000-0001-5023-0689; Jaffe, Elaine/0000-0003-4632-0301 FU National Cancer Institute, National Institutes of Health [1U01CA157581-01]; Lymphoma Foundation of America; Lymphoma Research Foundation; Leukemia & Lymphoma Society; University of Nebraska Medical Center-Clinical and Translational Research mentored Scholars program pilot grant; Chinese Scholarship Council FX The study was supported by the National Cancer Institute, National Institutes of Health (1U01CA157581-01). J.I. is a recipient of the young scientist award from the Lymphoma Foundation of America, a fellowship from the Lymphoma Research Foundation, and the Translational Research Program award from the Leukemia & Lymphoma Society, and has also received a University of Nebraska Medical Center-Clinical and Translational Research mentored Scholars program pilot grant. C.W. is a recipient of a fellowship from the Chinese Scholarship Council. NR 37 TC 66 Z9 71 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 MAY 8 PY 2014 VL 123 IS 19 BP 2915 EP 2923 DI 10.1182/blood-2013-11-536359 PG 9 WC Hematology SC Hematology GA AH1RF UT WOS:000335897900009 PM 24632715 ER PT J AU Steward-Tharp, SM Laurence, A Kanno, Y Kotlyar, A Villarino, AV Sciume, G Kuchen, S Resch, W Wohlfert, EA Jiang, K Hirahara, K Vahedi, G Sun, HW Feigenbaum, L Milner, JD Holland, SM Casellas, R Powrie, F O'Shea, JJ AF Steward-Tharp, Scott M. Laurence, Arian Kanno, Yuka Kotlyar, Alex Villarino, Alejandro V. Sciume, Giuseppe Kuchen, Stefan Resch, Wolfgang Wohlfert, Elizabeth A. Jiang, Kan Hirahara, Kiyoshi Vahedi, Golnaz Sun, Hong-wei Feigenbaum, Lionel Milner, Joshua D. Holland, Steven M. Casellas, Rafael Powrie, Fiona O'Shea, John J. TI A mouse model of HIES reveals pro- and anti-inflammatory functions of STAT3 SO BLOOD LA English DT Article ID HYPER-IGE SYNDROME; INDUCED TH2 POLARIZATION; HYPERIMMUNOGLOBULINEMIA-E; T-CELLS; B-CELLS; MUTATIONS; DISEASE; MICE; PATHOGENESIS; GENERATION AB Mutations of STAT3 underlie the autosomal dominant form of hyperimmunoglobulin E syndrome (HIES). STAT3 has critical roles in immune cells and thus, hematopoietic stem cell transplantation (HSCT), might be a reasonable therapeutic strategy in this disease. However, STAT3 also has critical functions in nonhematopoietic cells and dissecting the protean roles of STAT3 is limited by the lethality associated with germline deletion of Stat3. Thus, predicting the efficacy of HSCT for HIES is difficult. To begin to dissect the importance of STAT3 in hematopoietic and nonhematopoietic cells as it relates to HIES, we generated a mouse model of this disease. We found that these transgenic mice recapitulate multiple aspects of HIES, including elevated serum IgE and failure to generate Th17 cells. We found that these mice were susceptible to bacterial infection that was partially corrected by HSCT using wild-type bone marrow, emphasizing the role played by the epithelium in the pathophysiology of HIES. C1 [Steward-Tharp, Scott M.; Laurence, Arian; Kanno, Yuka; Kotlyar, Alex; Villarino, Alejandro V.; Sciume, Giuseppe; Jiang, Kan; Hirahara, Kiyoshi; Vahedi, Golnaz; O'Shea, John J.] NIAMSD, Mol Immunol & Inflammat Branch, NIH, Bethesda, MD 20892 USA. [Steward-Tharp, Scott M.; Powrie, Fiona] Univ Oxford, Sir William Dunn Sch Pathol, Oxford OX1 2JD, England. [Kuchen, Stefan; Resch, Wolfgang; Casellas, Rafael] NIAMSD, NIH, Bethesda, MD 20892 USA. [Wohlfert, Elizabeth A.] SUNY Buffalo, Dept Microbiol & Immunol, Sch Med & Biomed Sci, Buffalo, NY 14260 USA. [Sun, Hong-wei] NIAMSD, Biodata Min & Discovery Sect, NIH, Bethesda, MD 20892 USA. [Feigenbaum, Lionel] NCI, Lab Anim Sci Program, NIH, Frederick, MD 21701 USA. [Milner, Joshua D.] NIAID, Lab Allerg Dis, NIH, Bethesda, MD 20892 USA. [Holland, Steven M.] NIAID, NIH, Bethesda, MD 20892 USA. RP Laurence, A (reprint author), NIAMSD, Mol Immunol & Inflammat Branch, NIH, 10 Ctr Dr,MSC 1930,Bldg 10,Room 13C120-11B, Bethesda, MD 20892 USA. EM laurencea@mail.nih.gov RI Kanno, Yuka/B-5802-2013; Laurence, Arian/A-8770-2009; Sciume, Giuseppe/K-8985-2016; Hirahara, Kiyoshi/E-2460-2017; OI Laurence, Arian/0000-0003-0942-8292; Sciume, Giuseppe/0000-0003-0131-512X; Hirahara, Kiyoshi/0000-0002-9128-9449; Kuchen, Stefan/0000-0003-4899-8132; Kanno, Yuka/0000-0001-5668-9319; Villarino, Alejandro/0000-0001-8068-2176 FU Howard Hughes Medical Institute-National Institutes of Health; National Institute of Arthritis and Musculoskeletal and Skin Diseases of the National Institutes of Health FX S.M.S.-T. is a member of the National Institutes of Health-Oxford/Cambridge Scholars Program. A. K. and S.M.S.-T. were funded by the Howard Hughes Medical Institute-National Institutes of Health research scholar program.; This work was supported in part by the Intramural Research Program of the National Institute of Arthritis and Musculoskeletal and Skin Diseases of the National Institutes of Health. NR 46 TC 20 Z9 21 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 MAY 8 PY 2014 VL 123 IS 19 BP 2978 EP 2987 DI 10.1182/blood-2013-09-523167 PG 10 WC Hematology SC Hematology GA AH1RF UT WOS:000335897900016 PM 24632714 ER PT J AU Wang, PP Zhou, ZH Hu, AC de Albuquerque, CP Zhou, Y Hong, LX Sierecki, E Ajiro, M Kruhlak, M Harris, C Guan, KL Zheng, ZM Newton, AC Sun, PQ Zhou, HL Fu, XD AF Wang, Pingping Zhou, Zhihong Hu, Anchang de Albuquerque, Claudio Ponte Zhou, Yu Hong, Lixin Sierecki, Emma Ajiro, Masahiko Kruhlak, Michael Harris, Curtis Guan, Kun-Liang Zheng, Zhi-Ming Newton, Alexandra C. Sun, Peiqing Zhou, Huilin Fu, Xiang-Dong TI Both Decreased and Increased SRPK1 Levels Promote Cancer by Interfering with PHLPP- Mediated Dephosphorylation of Akt SO MOLECULAR CELL LA English DT Article ID SPLICING-FACTOR; SR PROTEINS; CELLULAR SENESCENCE; TUMOR-SUPPRESSOR; MAMMALIAN-CELLS; WIDE ANALYSIS; RNA; PHOSPHORYLATION; PHOSPHATASE; ACTIVATION AB Akt activation is a hallmark of human cancers. Here, we report a critical mechanism for regulation of Akt activity by the splicing kinase SRPK1, a downstream Akt target for transducing growth signals to regulate splicing. Surprisingly, we find that SRPK1 has a tumor suppressor function because ablation of SRPK1 in mouse embryonic fibroblasts induces cell transformation. We link the phenotype to constitutive Akt activation from genome-wide phosphoproteomics analysis and discover that downregulated SRPK1 impairs the recruitment of the Akt phosphatase PHLPP1 (pleckstrin homology (PH) domain leucine-rich repeat protein phosphatase) to Akt. Interestingly, SRPK1 overexpression is also tumorigenic because excess SRPK1 squelches PHLPP1. Thus, aberrant SRPK1 expression in either direction induces constitutive Akt activation, providing a mechanistic basis for previous observations that SRPK1 is downregulated in some cancer contexts and upregulated in others. C1 [Wang, Pingping; Zhou, Zhihong; Hu, Anchang; de Albuquerque, Claudio Ponte; Zhou, Yu; Zhou, Huilin; Fu, Xiang-Dong] Univ Calif San Diego, Dept Cellular & Mol Med, La Jolla, CA 92093 USA. [de Albuquerque, Claudio Ponte; Zhou, Huilin] Univ Calif San Diego, Ludwig Inst Canc Res, La Jolla, CA 92093 USA. [Hong, Lixin; Sun, Peiqing] Scripps Res Inst, Dept Cell & Mol Biol, La Jolla, CA 92037 USA. [Sierecki, Emma; Guan, Kun-Liang; Newton, Alexandra C.] Univ Calif San Diego, Dept Pharmacol, La Jolla, CA 92093 USA. [Ajiro, Masahiko; Zheng, Zhi-Ming] NCI, Tumor Virus RNA Biol Sect, Gene Regulat & Chromosome Biol Lab, Bethesda, MD 20892 USA. [Kruhlak, Michael] NCI, Expt Immunol Branch, Ctr Canc Res, Bethesda, MD 20892 USA. [Harris, Curtis] NCI, Human Carcinogenesis Lab, Bethesda, MD 20892 USA. [Fu, Xiang-Dong] Univ Calif San Diego, Inst Genom Med, La Jolla, CA 92093 USA. RP Fu, XD (reprint author), Univ Calif San Diego, Dept Cellular & Mol Med, La Jolla, CA 92093 USA. EM xdfu@ucsd.edu RI Sierecki, Emma/A-4810-2012 FU NIH [GM052872, GM067946] FX We thank members of the Fu lab for stimulating discussion during the course of this investigation. This work was supported by NIH grants (GM052872 to X.-D.F. and GM067946 to A.C.N.). H.Z. is an investigator of the Ludwig Institute for Cancer Research. NR 47 TC 25 Z9 26 U1 3 U2 10 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 MAY 8 PY 2014 VL 54 IS 3 BP 378 EP 391 DI 10.1016/j.molcel.2014.03.007 PG 14 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA AH3ME UT WOS:000336026900007 PM 24703948 ER PT J AU Liang, YH Lavoie, M Comeau, MA Abou Elela, S Ji, XH AF Liang, Yu-He Lavoie, Mathieu Comeau, Marc-Andre Abou Elela, Sherif Ji, Xinhua TI Structure of a Eukaryotic RNase III Postcleavage Complex Reveals a Double-Ruler Mechanism for Substrate Selection SO MOLECULAR CELL LA English DT Article ID DOUBLE-STRANDED-RNA; RIBONUCLEASE-III; BINDING DOMAIN; HUMAN DICER; CLEAVAGE ACTIVITY; ESCHERICHIA-COLI; MESSENGER-RNAS; YEAST; RNT1P; RECOGNITION AB Ribonuclease III (RNase III) enzymes are a family of double-stranded RNA (dsRNA)-specific endoribonucleases required for RNA maturation and gene regulation. Prokaryotic RNase III enzymes have been well characterized, but how eukaryotic RNase IIIs work is less clear. Here, we describe the structure of the Saccharomyces cerevisiae RNase III (Rnt1p) post-cleavage complex and explain why Rnt1p binds to RNA stems capped with an NGNN tetraloop. The structure shows specific interactions between a structural motif located at the end of the Rnt1p dsRNA-binding domain (dsRBD) and the guanine nucleotide in the second position of the loop. Strikingly, structural and biochemical analyses indicate that the dsRBD and N-terminal domains (NTDs) of Rnt1p function as two rulers that measure the distance between the tetraloop and the cleavage site. These findings provide a framework for understanding eukaryotic RNase IIIs. C1 [Liang, Yu-He; Ji, Xinhua] NCI, Biomol Struct Sect, Macromol Crystallog Lab, Frederick, MD 21702 USA. [Lavoie, Mathieu; Comeau, Marc-Andre; Abou Elela, Sherif] Univ Sherbrooke, Dept Microbiol & Infectiol, RNA Grp, Grp ARN, Sherbrooke, PQ J1E 4K8, Canada. RP Abou Elela, S (reprint author), Univ Sherbrooke, Dept Microbiol & Infectiol, RNA Grp, Grp ARN, Sherbrooke, PQ J1E 4K8, Canada. EM sherif.abou.elela@usherbrooke.ca; jix@mail.nih.gov FU NIH, National Cancer Institute, Center for Cancer Research; Canadian Institute of Health Research FX We thank Catherine Desrosiers for help with protein purification, Jules Gagnon for tetraloop sequence conservation analysis, and Donald Court, George Mackie, and Alexander Wlodawer for discussion. X-ray diffraction data were collected at the SER-CAT 22-ID beamline of the Advanced Photon Source, Argonne National Laboratory. This research was supported by the Intramural Research Program of the NIH, National Cancer Institute, Center for Cancer Research (X.J.) and a grant from the Canadian Institute of Health Research (S.A.E.). NR 47 TC 10 Z9 10 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 MAY 8 PY 2014 VL 54 IS 3 BP 431 EP 444 DI 10.1016/j.molcel.2014.03.006 PG 14 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA AH3ME UT WOS:000336026900011 PM 24703949 ER PT J AU Fang, EF Scheibye-Knudsen, M Brace, LE Kassahun, H SenGupta, T Nilsen, H Mitchell, JR Croteau, DL Bohr, VA AF Fang, Evandro Fei Scheibye-Knudsen, Morten Brace, Lear E. Kassahun, Henok SenGupta, Tanima Nilsen, Hilde Mitchell, James R. Croteau, Deborah L. Bohr, Vilhelm A. TI Defective Mitophagy in XPA via PARP-1 Hyperactivation and NAD(+)/SIRT1 Reduction SO CELL LA English DT Article ID PIGMENTOSUM GROUP-A; COCKAYNE-SYNDROME; XERODERMA-PIGMENTOSUM; DNA-REPAIR; UNCOUPLING PROTEIN-2; PARKINSONS-DISEASE; MOUSE MODEL; AUTOPHAGY; DAMAGE; MITOCHONDRIA AB Mitochondrial dysfunction is a common feature in neurodegeneration and aging. We identify mitochondrial dysfunction in xeroderma pigmentosum group A (XPA), a nucleotide excision DNA repair disorder with severe neurodegeneration, in silico and in vivo. XPA-deficient cells show defective mitophagy with excessive cleavage of PINK1 and increased mitochondrial membrane potential. The mitochondrial abnormalities appear to be caused by decreased activation of the NAD(+)-SIRT1-PGC-1 alpha axis triggered by hyperactivation of the DNA damage sensor PARP1. This phenotype is rescued by PARP-1 inhibition or by supplementation with NAD(+) precursors that also rescue the lifespan defect in xpa-1 nematodes. Importantly, this pathogenesis appears common to ataxia-telangiectasia and Cockayne syndrome, two other DNA repair disorders with neurodegeneration, but absent in XPC, a DNA repair disorder without neurodegeneration. Our findings reveal a nuclear-mitochondrial crosstalk that is critical for the maintenance of mitochondrial health. C1 [Fang, Evandro Fei; Scheibye-Knudsen, Morten; Croteau, Deborah L.; Bohr, Vilhelm A.] NIA, Lab Mol Gerontol, NIH, Baltimore, MD 21224 USA. [Brace, Lear E.; Mitchell, James R.] Harvard Univ, Sch Med, Dept Genet & Complex Dis, Boston, MA 02115 USA. [Kassahun, Henok; SenGupta, Tanima; Nilsen, Hilde] Univ Oslo, Ctr Biotechnol, N-0317 Oslo, Norway. [Bohr, Vilhelm A.] Univ Copenhagen, Danish Ctr Hlth Aging, DK-2200 Copenhagen, Denmark. RP Bohr, VA (reprint author), NIA, Lab Mol Gerontol, NIH, Baltimore, MD 21224 USA. EM vbohr@nih.gov OI Scheibye-Knudsen, Morten/0000-0002-6637-1280 FU Intramural Research Program of the NIH, National Institute on Aging; research council of Norway; Luke O'Brien Foundation; National Science Foundation Graduate Research Fellowship Program FX We thank Drs. Kevin Becker, Yongqing Zhang, and Elin Lehrmann for their help in performing microarray and data analysis, and Dr. Magdalena Misiak for preparing rat neurons. We thank Drs. Mark Mattson and Peter Sykora for reading this manuscript. This research was supported by the Intramural Research Program of the NIH, National Institute on Aging. H.N. was supported by a grant from the research council of Norway. J.R.M. and L.E.B. were supported by the Luke O'Brien Foundation, and L.E.B. was supported by the National Science Foundation Graduate Research Fellowship Program. NR 29 TC 86 Z9 86 U1 4 U2 33 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 MAY 8 PY 2014 VL 157 IS 4 BP 882 EP 896 DI 10.1016/j.cell.2014.03.026 PG 15 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA AG9UN UT WOS:000335765500016 PM 24813611 ER PT J AU Naidoo, J De Jesus-Cortes, H Huntington, P Estill, S Morlock, LK Starwalt, R Mangano, TJ Williams, NS Pieper, AA Ready, JM AF Naidoo, Jacinth De Jesus-Cortes, Hector Huntington, Paula Estill, Sandi Morlock, Lorraine K. Starwalt, Ruth Mangano, Thomas J. Williams, Noelle S. Pieper, Andrew A. Ready, Joseph M. TI Discovery of a Neuroprotective Chemical, (S)-N-(3-(3,6-Dibromo-9H-carbazol-9-yl)-2-fluoropropyl)-6-methoxypyridin -2-amine [(-)-P7C3-S243], with Improved Druglike Properties SO JOURNAL OF MEDICINAL CHEMISTRY LA English DT Article ID MOUSE MODEL; AMINOPROPYL CARBAZOLES; PARKINSONS-DISEASE; DERIVATIVES; MPTP; NEUROTOXIN; EFFICACY AB (-)-P7C3-S243 is a neuroprotective aminopropyl carbazole with improved druglike properties compared with previously reported compounds in the P7C3 class. It protects developing neurons in a mouse model of hippocampal neurogenesis and protects mature neurons within the substantia nigra in a mouse model of Parkinson's disease. A short, enantioselective synthesis provides the neuroprotective agent in optically pure form. It is nontoxic, orally bioavailable, metabolically stable, and able to cross the blood-brain barrier. As such, it represents a valuable lead compound for the development of drugs to treat neurodegenerative diseases and traumatic brain injury. C1 [Naidoo, Jacinth; Huntington, Paula; Estill, Sandi; Morlock, Lorraine K.; Starwalt, Ruth; Williams, Noelle S.; Ready, Joseph M.] Univ Texas SW Med Ctr Dallas, Dept Biochem, Dallas, TX 75390 USA. [De Jesus-Cortes, Hector] Univ Texas SW Med Ctr Dallas, Dept Neurosci, Dallas, TX 75390 USA. [De Jesus-Cortes, Hector; Pieper, Andrew A.] Univ Iowa, Dept Psychiat, Carver Coll Med, Iowa City, IA 52242 USA. [De Jesus-Cortes, Hector; Pieper, Andrew A.] Univ Iowa, Dept Neurol, Carver Coll Med, Iowa City, IA 52242 USA. [De Jesus-Cortes, Hector; Pieper, Andrew A.] Univ Iowa, Dept Vet Affairs, Carver Coll Med, Iowa City, IA 52242 USA. [Mangano, Thomas J.] Univ N Carolina, NIMH, Psychoact Drug Screening Program, Chapel Hill, NC 27599 USA. RP Pieper, AA (reprint author), Univ Iowa, Dept Psychiat, Carver Coll Med, Iowa City, IA 52242 USA. EM andrew-pieper@uiowa.edu; joseph.ready@utsouthwestern.edu OI De Jesus-Cortes, Hector/0000-0001-6983-6963 FU Edward N. and Della C. Thome Memorial Foundation; Welch Foundation [I-1612]; NSF [2012140236-02]; NIH [R01 MH087986] FX We thank Prof. Jef De Brabander (UT Southwestern) for helpful discussions regarding Cu-catalyzed amination and the NIH's Psychoactive Drug Screening Program at the University of North Carolina. Funding was provided by the Edward N. and Della C. Thome Memorial Foundation and the Welch Foundation (I-1612) (to J.M.R.) and the NSF (2012140236-02) (to H.D.J.-C.). Additional support was received from the NIH (R01 MH087986) to A.A.P. and an unrestricted endowment provided to Steven L. McKnight by an anonymous donor. NR 28 TC 16 Z9 17 U1 0 U2 16 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 MAY 8 PY 2014 VL 57 IS 9 BP 3746 EP 3754 DI 10.1021/jm401919s PG 9 WC Chemistry, Medicinal SC Pharmacology & Pharmacy GA AH1KN UT WOS:000335879100012 PM 24697290 ER PT J AU Pu, YM Kang, JH Sigano, DM Peach, ML Lewin, NE Marquez, VE Blumberg, PM AF Pu, Yongmei Kang, Ji-Hye Sigano, Dina M. Peach, Megan L. Lewin, Nancy E. Marquez, Victor E. Blumberg, Peter M. TI Diacylglycerol Lactones Targeting the Structural Features That Distinguish the Atypical C1 Domains of Protein Kinase C zeta and iota from Typical C1 Domains SO JOURNAL OF MEDICINAL CHEMISTRY LA English DT Article ID CONFORMATIONALLY CONSTRAINED ANALOGS; HIGH BINDING-AFFINITY; DAG-LACTONES; CRYSTAL-STRUCTURE; PHOSPHOLIPASE-D; PHORBOL ESTER; PK-C; ISOFORMS; LIGAND; RAS AB To explore the feasibility of developing ligands targeted to the atypical C1 domains of protein kinase C zeta and iota, we have prepared diacylglycerol lactones substituted with hydrophilic groups on their side chains, which potentially could interact with the arginine residues that distinguish the atypical C1 domains of PKC zeta and PKC?iota from typical C1 domains, and we have measured their binding to mutated versions of the C1b domain of PKC delta that incorporate one or more of these arginine residues. The most selective of the diacylglycerol lactones showed only a 10-fold reduction in binding affinity with the triple arginine mutant (N7R/S10R/L20R) compared to the wild-type, whereas phorbol 12,13-dibutyrate showed a 6000-fold loss of affinity. Molecular modeling confirms that these ligands are indeed able to interact with the arginine residues. Our results show that dramatic changes in selectivity can be obtained through appropriate substitution of diacylglycerol lactones. C1 [Pu, Yongmei; Lewin, Nancy E.; Blumberg, Peter M.] NCI, Lab Canc Biol & Genet, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. [Kang, Ji-Hye; Sigano, Dina M.; Marquez, Victor E.] NCI, Biol Chem Lab, Ctr Canc Res, NIH, Frederick, MD 21702 USA. [Peach, Megan L.] Leidos Biomed Inc, Biol Chem Lab, Basic Sci Program, Frederick Natl Lab Canc Res, Frederick, MD 21702 USA. RP Blumberg, PM (reprint author), NCI, Lab Canc Biol & Genet, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. EM blumberp@dc37a.nci.nih.gov RI Sigano, Dina/M-6144-2014 OI Sigano, Dina/0000-0001-7489-9555 FU National Institutes of Health, Center for Cancer Research, National Cancer Institute [Z1A BC 005270]; Federal funds from the Frederick National Laboratory for Cancer Research, National Institutes of Health [HHSN261200800001E] FX This work was supported in part through the Intramural Research Program of the National Institutes of Health, Center for Cancer Research, National Cancer Institute (Project Z1A BC 005270) and in part with Federal funds from the Frederick National Laboratory for Cancer Research, National Institutes of Health, under Contract HHSN261200800001E. The content of this publication does not necessarily reflect the views or policies of the Department of Health and Human Services, nor does mention of trade names, commercial products, or organizations imply endorsement by the U.S. Government. NR 44 TC 2 Z9 2 U1 2 U2 12 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 MAY 8 PY 2014 VL 57 IS 9 BP 3835 EP 3844 DI 10.1021/jm500165n PG 10 WC Chemistry, Medicinal SC Pharmacology & Pharmacy GA AH1KN UT WOS:000335879100018 PM 24684293 ER PT J AU Jayasekara, PS Barrett, MO Ball, CB Brown, KA Hammes, E Balasubramanian, R Harden, TK Jacobson, KA AF Jayasekara, P. Suresh Barrett, Matthew O. Ball, Christopher B. Brown, Kyle A. Hammes, Eva Balasubramanian, Ramachandran Harden, T. Kendall Jacobson, Kenneth A. TI 4-Alkyloxyimino Derivatives of Uridine-5 '-triphosphate: Distal Modification of Potent Agonists as a Strategy for Molecular Probes of P2Y(2), P2Y(4), and P2Y(6) Receptors SO JOURNAL OF MEDICINAL CHEMISTRY LA English DT Article ID NUCLEOTIDE RECEPTORS; SELECTIVE AGONISTS; ANTAGONIST; ATP; UDP AB Extended N-4-(3-arylpropyl)oxy derivatives of uridine-5 '-triphosphate were synthesized and potently stimulated phospholipase C stimulation in astrocytoma cells expressing G protein-coupled human (h) P2Y receptors (P2YRs) activated by UTP (P2Y(2/4)R) or UDP (P2Y(6)R). The potent P2Y(4)R-selective N-4-(3-phenylpropyl)oxy agonist was phenyl ring-substituted or replaced with terminal heterocyclic or naphthyl rings with retention of P2YR potency. This broad tolerance for steric bulk in a distal region was not observed for dinucleoside tetraphosphate agonists with both nucleobases substituted. The potent N-4-(3-(4-methoxyphenyl)-propyl)oxy analogue 19 (EC50: P2Y(2)R, 47 nM; P2Y(4)R, 23 nM) was functionalized for chain extension using click tethering of fluorophores as prosthetic groups. The BODIPY 630/650 conjugate 28 (MRS4162) exhibited EC50 values of 70, 66, and 23 nM at the hP2Y(2/4/6)Rs, respectively, and specifically labeled cells expressing the P2Y(6)R. Thus, an extended N-4-(3-arylpropyl)oxy group accessed a structurally permissive region on three G(q)-coupled P2YRs, and potency and selectivity were modulated by distal structural changes. This freedom of substitution was utilized to design of a pan-agonist fluorescent probe of a subset of uracil nucleotide-activated hP2YRs. C1 [Jayasekara, P. Suresh; Hammes, Eva; Balasubramanian, Ramachandran; Jacobson, Kenneth A.] NIDDK, Mol Recognit Sect, Bioorgan Chem Lab, NIH, Bethesda, MD 20892 USA. [Barrett, Matthew O.; Ball, Christopher B.; Brown, Kyle A.; Harden, T. Kendall] Univ N Carolina, Sch Med, Dept Pharmacol, Chapel Hill, NC 27599 USA. RP Jacobson, KA (reprint author), NIDDK, NIH, Bldg 8A,Rm 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 NIH, National Institute of Diabetes and Digestive and Kidney Diseases; National Institute of General Medical Sciences [GM38213] FX This research was supported in part by the Intramural Research Program of the NIH, National Institute of Diabetes and Digestive and Kidney Diseases, and a grant (GM38213) from the National Institute of General Medical Sciences. We thank Noel Whittaker (NIDDK) for mass spectral determinations. NR 34 TC 12 Z9 12 U1 1 U2 9 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 MAY 8 PY 2014 VL 57 IS 9 BP 3874 EP 3883 DI 10.1021/jm500367e PG 10 WC Chemistry, Medicinal SC Pharmacology & Pharmacy GA AH1KN UT WOS:000335879100021 PM 24712832 ER PT J AU Albert, S Balaban, RS Neufeld, EB Rossmann, JS AF Albert, Scott Balaban, Robert S. Neufeld, Edward B. Rossmann, Jenn Stroud TI Influence of the renal artery ostium flow diverter on hemodynamics and atherogenesis SO JOURNAL OF BIOMECHANICS LA English DT Article DE Renal artery; Ostium; Flow diverter; CFD; Cardiovascular; Atherosclerosis; Abdominal aorta ID ABDOMINAL-AORTA; BLOOD-FLOW; ATHEROSCLEROSIS; RABBITS; MODEL AB The structure and function of the renal artery ostium flow diverter on the caudal side of the renal branch point were previously reported; in this study, we further evaluate the diverter's possible functions. The protrusion of this structure into the abdominal aorta suggests that the diverter may preferentially direct blood flow to the renal arteries, and that it may also influence flow patterns and recirculation known to be involved in atherogenesis. Three-dimensional computational fluid dynamics (CFD) simulations of steady and pulsatile blood flow are performed to investigate the influence of diverter size and position, and vascular geometry, on the flow patterns and fluid mechanical forces in the neighborhood of the diverter. CFD results show that the flow diverter does affect the blood distribution; depending on the diverter's position, the flow to the renal arteries may be increased or reduced. Calculated results also demonstrate the diverter's effect on the wall shear stress (WSS) distribution, and suggest that the diverter contributes to an atherogenic environment in the abdominal aorta, while being atheroprotective in the renal arteries themselves. These results support previous clinical findings, and suggest directions for further clinical study. The results of this work have direct implications in understanding the physiological significance of the diverter, and its potential role in the pathophysiological development of atherosclerosis. (C) 2014 Elsevier Ltd. All rights reserved. C1 [Albert, Scott] Lafayette Coll, Chem & Biomol Engn Dept, Easton, PA 18042 USA. [Balaban, Robert S.; Neufeld, Edward B.] NHLBI, Cardiac Energet Lab, Bethesda, MD 20892 USA. [Rossmann, Jenn Stroud] Lafayette Coll, Dept Mech Engn, Easton, PA 18042 USA. RP Rossmann, JS (reprint author), Lafayette Coll, Dept Mech Engn, Easton, PA 18042 USA. EM rossmanj@lafayette.edu FU Lafayette College Departments of Mechanical and Chemical & Biomolecular Engineering FX The authors are grateful to the Lafayette College Departments of Mechanical and Chemical & Biomolecular Engineering, which supported the first author's completion of his undergraduate honors thesis on this subject. They also acknowledge the helpful contributions of Becky Rosenbauer, Peter Sun, Taimoor Sohail, Apratim Mukherjee, and Li-Yueh Hsu. NR 21 TC 4 Z9 4 U1 0 U2 6 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0021-9290 EI 1873-2380 J9 J BIOMECH JI J. Biomech. PD MAY 7 PY 2014 VL 47 IS 7 BP 1594 EP 1602 DI 10.1016/j.jbiomech.2014.03.006 PG 9 WC Biophysics; Engineering, Biomedical SC Biophysics; Engineering GA AI6VY UT WOS:000337016300006 PM 24703300 ER PT J AU Snow, KK Bell, MC Stoddard, AM Curto, TM Wright, EC Dienstag, JL AF Snow, Kristin K. Bell, Margaret C. Stoddard, Anne M. Curto, Teresa M. Wright, Elizabeth C. Dienstag, Jules L. TI Processes to manage analyses and publications in a phase III multicenter randomized clinical trial SO TRIALS LA English DT Article DE Publication guidelines; Publication processes; Publication management; HALT-C trial; Authorship assignment; Authorship allocation ID CHRONIC HEPATITIS-C; LONG-TERM TREATMENT; LOW-DOSE PEGINTERFERON; STANDARD LABORATORY TESTS; LIVER-DISEASE PROGRESSION; SERUM FIBROSIS MARKERS; QUALITY-OF-LIFE; CIRRHOSIS TRIAL; HEPATOCELLULAR-CARCINOMA; COGNITIVE FUNCTION AB Background: The timely publication of findings in peer-reviewed journals is a primary goal of clinical research. In clinical trials, the processes leading to publication can be complex from choice and prioritization of analytic topics through to journal submission and revisions. As little literature exists on the publication process for multicenter trials, we describe the development, implementation, and effectiveness of such a process in a multicenter trial. Methods: The Hepatitis C Antiviral Long-Term Treatment against Cirrhosis (HALT-C) trial included a data coordinating center (DCC) and clinical centers that recruited and followed more than 1,000 patients. Publication guidelines were approved by the steering committee, and the publications committee monitored the publication process from selection of topics to publication. Results: A total of 73 manuscripts were published in 23 peer-reviewed journals. When manuscripts were closely tracked, the median time for analyses and drafting of manuscripts was 8 months. The median time for data analyses was 5 months and the median time for manuscript drafting was 3 months. The median time for publications committee review, submission, and journal acceptance was 7 months, and the median time from analytic start to journal acceptance was 18 months. Conclusions: Effective publication guidelines must be comprehensive, implemented early in a trial, and require active management by study investigators. Successful collaboration, such as in the HALT-C trial, can serve as a model for others involved in multidisciplinary and multicenter research programs. C1 [Snow, Kristin K.; Bell, Margaret C.; Stoddard, Anne M.; Curto, Teresa M.] New England Res Inst, Watertown, MA 02472 USA. [Snow, Kristin K.] New Hampshire Dept Hlth & Human Serv, Bur Publ Hlth Stat & Informat, Div Publ Hlth Serv, Concord, NH 03301 USA. [Wright, Elizabeth C.] NIDDK, Off Director, NIH, Bethesda, MD 20892 USA. [Dienstag, Jules L.] Massachusetts Gen Hosp, Gastrointestinal Unit, Boston, MA 02114 USA. [Dienstag, Jules L.] Harvard Univ, Sch Med, Dept Med, Boston, MA 02115 USA. RP Curto, TM (reprint author), New England Res Inst, 9 Galen St, Watertown, MA 02472 USA. EM tcurto@neriscience.com FU National Institute of Diabetes and Digestive and Kidney Diseases [N01-DK-9-2326, N01-DK-9-2324, N01-DK- 9-2319, N01-DK-9-2327, N01-DK-9-2320, N01-DK-9-2321, N01-DK-9-2325, N01-DK-9-2323, N01-DK-9-2322, N01-DK-9-2318, N01-DK-9-2328]; Hoffmann-La Roche, through a cooperative research and development agreement; National Institutes of Health FX We acknowledge the HALT-C Trial group for providing data for this publication. The HALT-C trial was supported by National Institute of Diabetes and Digestive and Kidney Diseases contracts N01-DK-9-2326, N01-DK-9-2324, contract N01-DK- 9-2319, N01-DK-9-2327, N01-DK-9-2320, N01-DK-9-2321, N01-DK-9-2325, N01-DK-9-2323, N01-DK-9-2322, N01-DK-9-2318, and N01-DK-9-2328. Additional financial support was provided by Hoffmann-La Roche, through a cooperative research and development agreement with the National Institutes of Health. NR 85 TC 0 Z9 0 U1 0 U2 0 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1745-6215 J9 TRIALS JI Trials PD MAY 7 PY 2014 VL 15 AR 159 DI 10.1186/1745-6215-15-159 PG 12 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA AI3ZV UT WOS:000336805600001 PM 24886378 ER PT J AU Knott, M Best, RB AF Knott, Michael Best, Robert B. TI Discriminating binding mechanisms of an intrinsically disordered protein via a multi-state coarse-grained model SO JOURNAL OF CHEMICAL PHYSICS LA English DT Article ID SINGLE-MOLECULE SPECTROSCOPY; CONFORMATIONAL SELECTION; INDUCED-FIT; ADENYLATE KINASE; TRANSITION-STATE; COUPLED BINDING; TRANSFER-RNA; DOMAIN; DYNAMICS; RECOGNITION AB Many proteins undergo a conformational transition upon binding to their cognate binding partner, with intrinsically disordered proteins (IDPs) providing an extreme example in which a folding transition occurs. However, it is often not clear whether this occurs via an "induced fit" or "conformational selection" mechanism, or via some intermediate scenario. In the first case, transient encounters with the binding partner favour transitions to the bound structure before the two proteins dissociate, while in the second the bound structure must be selected from a subset of unbound structures which are in the correct state for binding, because transient encounters of the incorrect conformation with the binding partner are most likely to result in dissociation. A particularly interesting situation involves those intrinsically disordered proteins which can bind to different binding partners in different conformations. We have devised a multi-state coarse-grained simulation model which is able to capture the binding of IDPs in alternate conformations, and by applying it to the binding of nuclear coactivator binding domain (NCBD) to either ACTR or IRF-3 we are able to determine the binding mechanism. By all measures, the binding of NCBD to either binding partner appears to occur via an induced fit mechanism. Nonetheless, we also show how a scenario closer to conformational selection could arise by choosing an alternative non-binding structure for NCBD. (C) 2014 AIP Publishing LLC. C1 [Knott, Michael; Best, Robert B.] Univ Cambridge, Dept Chem, Cambridge CB2 1EW, England. [Best, Robert B.] NIDDK, Chem Phys Lab, NIH, Bethesda, MD 20892 USA. RP Knott, M (reprint author), Univ Cambridge, Dept Chem, Lensfield Rd, Cambridge CB2 1EW, England. EM robertbe@helix.nih.gov RI Best, Robert/H-7588-2016 OI Best, Robert/0000-0002-7893-3543 FU BBSRC [BB/H006885/1]; Royal Society University Research Fellowship at Cambridge; National Institute of Diabetes and Digestive and Kidney Diseases of the National Institutes of Health FX We thank Chris Baker and David de Sancho for many helpful suggestions and comments on the manuscript. M. K. and R. B. B. were supported by BBSRC Award No. BB/H006885/1. R. B. B. was supported by a Royal Society University Research Fellowship while at Cambridge and by the Intramural Research Program of the National Institute of Diabetes and Digestive and Kidney Diseases of the National Institutes of Health. NR 88 TC 12 Z9 12 U1 2 U2 20 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 MAY 7 PY 2014 VL 140 IS 17 AR 175102 DI 10.1063/1.4873710 PG 10 WC Chemistry, Physical; Physics, Atomic, Molecular & Chemical SC Chemistry; Physics GA AH3TI UT WOS:000336048000050 PM 24811666 ER PT J AU Justinova, Z Redhi, GH Goldberg, SR Ferre, S AF Justinova, Zuzana Redhi, Godfrey H. Goldberg, Steven R. Ferre, Sergi TI Differential Effects of Presynaptic versus Postsynaptic Adenosine A(2A) Receptor Blockade on Delta(9)-Tetrahydrocannabinol (THC) Self-Administration in Squirrel Monkeys SO JOURNAL OF NEUROSCIENCE LA English DT Article DE adenosine A2A receptor; cannabinoids; drug abuse; monkey; self-administration; THC ID VENTRAL TEGMENTAL AREA; NICOTINIC RECEPTORS; KYNURENIC ACID; DOPAMINE; ABUSE; RAT; NEUROTRANSMISSION; ACCUMBENS; BEHAVIOR; RELEASE AB Different doses of an adenosine A(2A) receptor antagonist MSX-3 [3,7-dihydro-8-[(1E)-2-(3-ethoxyphenyl) ethenyl]-7 methyl-3-[3( phosphooxy) propyl-1-(2 propynil)-1H-purine-2,6-dione] were found previously to either decrease or increase self-administration of cannabinoids delta-9-tetrahydrocannabinol (THC) or anandamide in squirrel monkeys. It was hypothesized that the decrease observed with a relatively low dose of MSX-3 was related to blockade of striatal presynaptic A(2A) receptors that modulate glutamatergic neurotransmission, whereas the increase observed with a higher dose was related to blockade of postsynapticA(2A) receptors localized in striatopallidal neurons. This hypothesis was confirmed in the present study by testing the effects of the preferential presynaptic and postsynaptic A(2A) receptor antagonists SCH-442416 [2-(2-furanyl)-7-[3-(4-methoxyphenyl) propyl]-7H-pyrazolo[4,3-e][1,2,4] triazolo[1,5-c] pyrimidin-5-amine] and KW-6002 [(E)-1, 3-diethyl-8-(3,4-dimethoxystyryl)-7-methyl-3,7-dihydro-1H-purine-2,6-dione], respectively, in squirrel monkeys trained to intravenously selfadminister THC. SCH-442416 produced a significant shift to the right of the THC self-administration dose-response curves, consistent with antagonism of the reinforcing effects of THC. Conversely, KW-6002 produced a significant shift to the left, consistent with potentiation of the reinforcing effects of THC. These results show that selectively blocking presynaptic A(2A) receptors could provide a new pharmacological approach to the treatment of marijuana dependence and underscore corticostriatal glutamatergic neurotransmission as a possible main mechanism involved in the rewarding effects of THC. C1 [Justinova, Zuzana; Redhi, Godfrey H.; Goldberg, Steven R.] Natl Inst Drug Abuse, Preclin Pharmacol Sect, Behav Neurosci Res Branch, Intramural Res Program,NIH,Dept Hlth & Human Serv, Baltimore, MD 21224 USA. [Ferre, Sergi] Natl Inst Drug Abuse, Integrat Neurobiol Sect, Mol Targets & Medicat Discovery Branch, Intramural Res Program,NIH,Dept Hlth & Human Serv, Baltimore, MD 21224 USA. RP Ferre, S (reprint author), Natl Inst Drug Abuse, Integrat Neurobiol Sect, Intramural Res Program, NIH, 333 Cassell Dr, Baltimore, MD 21224 USA. EM sferre@mail.nih.gov RI Ferre, Sergi/K-6115-2014; Justinova, Zuzana/A-9109-2011 OI Ferre, Sergi/0000-0002-1747-1779; Justinova, Zuzana/0000-0001-5793-7484 FU Intramural Research Program of the National Institute on Drug Abuse (NIDA), National Institutes of Health, Department of Health and Human Services FX This work was supported by the Intramural Research Program of the National Institute on Drug Abuse (NIDA), National Institutes of Health, Department of Health and Human Services. THC was provided by the NIDA Drug Supply Program. We thank Dr. Leigh V. Panlilio for his excellent assistance with statistical analysis. NR 21 TC 10 Z9 10 U1 1 U2 14 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 MAY 7 PY 2014 VL 34 IS 19 BP 6480 EP 6484 DI 10.1523/JNEUROSCI.5073-13.2014 PG 5 WC Neurosciences SC Neurosciences & Neurology GA AH8IF UT WOS:000336380500007 PM 24806674 ER PT J AU Ren, M Cao, V Ye, YZ Manji, HK Wang, KH AF Ren, Ming Cao, Vania Ye, Yizhou Manji, Husseini K. Wang, Kuan Hong TI Arc Regulates Experience-Dependent Persistent Firing Patterns in Frontal Cortex SO JOURNAL OF NEUROSCIENCE LA English DT Article DE Arc/Arg3.1; experience dependent; frontal cortex; NMDA receptor; persistent activity ID IMMEDIATE-EARLY GENE; PREFRONTAL CORTEX; IN-VIVO; RECEPTOR TRAFFICKING; SYNAPTIC PLASTICITY; NEURAL CIRCUITS; NMDA RECEPTORS; ACTIVE NEURONS; MEMORY; ARC/ARG3.1 AB The brain encodes information about past experience in specific populations of neurons that communicate with one another by firing action potentials. Studies of experience-dependent neural plasticity have largely focused on individual synaptic changes in response to neuronal input. Indicative of the neuronal output transmitted to downstream neurons, persistent firing patterns are affected by prior experience in selective neuronal populations. However, little is known about the molecular and cellular mechanisms by which experience-related persistent firing patterns are regulated in specific neuronal populations. Using frontal cortical slices prepared from transgenic mice carrying a fluorescent reporter of Arc gene expression, this study investigates how behavioral experience and the activity-regulated Arc gene affect patterns of neuronal firing. We found that motor training increases Arc expression in subsets of excitatory neurons. Those neurons exhibit persistent firing in contrast to Arc-negative neurons from the same mice or neurons from the untrained mice. Furthermore, in mice carrying genetic deletion of Arc, the frontal cortical circuitry is still in place to initiate experience-dependent gene expression, but the level of persistent firing thereafter is diminished. Finally, our results showed that the emergence of persistent activity is associated with Arc-dependent changes in the function of NMDA-type glutamate receptors, rather than changes in AMPA-type receptors or membrane excitability. Our findings therefore reveal an Arc-dependent molecular pathway by which geneexperience interaction regulates the emergence of persistent firing patterns in specific neuronal populations. C1 [Ren, Ming; Cao, Vania; Ye, Yizhou; Wang, Kuan Hong] NIMH, Unit Neural Circuits & Adapt Behav, Genes Cognit & Psychosis Program, NIH, Bethesda, MD 20892 USA. [Manji, Husseini K.] NIMH, Lab Mol Pathophysiol & Expt Therapeut, Mood & Anxiety Disorders Program, NIH, Bethesda, MD 20892 USA. RP Wang, KH (reprint author), NIMH, Unit Neural Circuits & Adapt Behav, Genes Cognit & Psychosis Program, NIH, Bethesda, MD 20892 USA. EM wkuan@mail.nih.gov RI Wang, Kuan Hong/J-1150-2016 OI Wang, Kuan Hong/0000-0002-2249-5417 FU National Institute of Mental Health (NIMH) Intramural Research Program; National Alliance for Research on Schizophrenia and Depression Young Investigator Award; NIMH Division of Intramural Research Programs; Genes Cognition and Psychosis Program FX This work was supported by the National Institute of Mental Health (NIMH) Intramural Research Program (M.R., V.C., Y.Y., H.K.M., K.H.W.) and a National Alliance for Research on Schizophrenia and Depression Young Investigator Award (M.R.). We thank T.R. Insel, D.R. Weinberger, P.S. Wang, M.E. Greenberg, and W.G. Chen for their critical reading of the manuscript and helpful discussions, and E.J. Sherman for technical editing. K.H.W. acknowledges the support of the NIMH Division of Intramural Research Programs and the Genes Cognition and Psychosis Program. NR 53 TC 11 Z9 12 U1 1 U2 13 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 MAY 7 PY 2014 VL 34 IS 19 BP 6583 EP 6595 DI 10.1523/JNEUROSCI.0167-14.2014 PG 13 WC Neurosciences SC Neurosciences & Neurology GA AH8IF UT WOS:000336380500016 PM 24806683 ER PT J AU Lin, HH Yin, XY Lunetta, KL Dupuis, J McManus, DD Lubitz, SA Magnani, JW Joehanes, R Munson, PJ Larson, MG Levy, D Ellinor, PT Benjamin, EJ AF Lin, Honghuang Yin, Xiaoyan Lunetta, Kathryn L. Dupuis, Josee McManus, David D. Lubitz, Steven A. Magnani, Jared W. Joehanes, Roby Munson, Peter J. Larson, Martin G. Levy, Daniel Ellinor, Patrick T. Benjamin, Emelia J. TI Whole Blood Gene Expression and Atrial Fibrillation: The Framingham Heart Study SO PLOS ONE LA English DT Article ID GENOME-WIDE ASSOCIATION; C-REACTIVE PROTEIN; FAMILIAL AGGREGATION; RISK-FACTOR; DISEASE; HYPOXIA; PREVALENCE; NETWORKS; HYPERTENSION; POLYMORPHISM AB Background: Atrial fibrillation (AF) involves substantial electrophysiological, structural and contractile remodeling. We hypothesize that characterizing gene expression might uncover important pathways related to AF. Methods and Results: We performed genome-wide whole blood transcriptomic profiling (Affymetrix Human Exon 1.0 ST Array) of 2446 participants (mean age 66 +/- 9 years, 55% women) from the Offspring cohort of Framingham Heart Study. The study included 177 participants with prevalent AF, 143 with incident AF during up to 7 years follow up, and 2126 participants with no AF. We identified seven genes statistically significantly up-regulated with prevalent AF. The most significant gene, PBX1 (P=2.8x10(-7)), plays an important role in cardiovascular development. We integrated differential gene expression with gene-gene interaction information to identify several signaling pathways possibly involved in AF-related transcriptional regulation. We did not detect any statistically significant transcriptomic associations with incident AF. Conclusion: We examined associations of gene expression with AF in a large community-based cohort. Our study revealed several genes and signaling pathways that are potentially involved in AF-related transcriptional regulation. C1 [Lin, Honghuang] Boston Univ, Sch Med, Dept Med, Sect Computat Biomed, Boston, MA 02215 USA. [Lin, Honghuang; Yin, Xiaoyan; Lunetta, Kathryn L.; Dupuis, Josee; McManus, David D.; Joehanes, Roby; Munson, Peter J.; Larson, Martin G.; Levy, Daniel; Benjamin, Emelia J.] NHLBI, Framingham, MA USA. [Lin, Honghuang; Yin, Xiaoyan; Lunetta, Kathryn L.; Dupuis, Josee; McManus, David D.; Joehanes, Roby; Munson, Peter J.; Larson, Martin G.; Levy, Daniel; Benjamin, Emelia J.] Boston Univ, Framingham Heart Study, Framingham, MA USA. [Lunetta, Kathryn L.; Dupuis, Josee] Boston Univ, Sch Publ Hlth, Dept Biostat, Boston, MA USA. [McManus, David D.] Univ Massachusetts, Sch Med, Dept Med, Div Cardiol, Worcester, MA USA. [McManus, David D.] Univ Massachusetts, Sch Med, Div Epidemiol, Dept Quantitat Hlth Sci, Worcester, MA USA. [Lubitz, Steven A.; Ellinor, Patrick T.] Massachusetts Gen Hosp, Cardiovasc Res Ctr, Charlestown, MA USA. [Magnani, Jared W.; Benjamin, Emelia J.] Boston Univ, Sch Med, Dept Med, Sect Cardiovasc Med, Boston, MA 02118 USA. [Joehanes, Roby; Munson, Peter J.] NIH, Math & Stat Comp Lab, Ctr Informat Technol, Bethesda, MD 20892 USA. [Joehanes, Roby; Munson, Peter J.; Levy, Daniel] NHLBI, Populat Sci Branch, Div Intramural Res, Bethesda, MD 20892 USA. [Larson, Martin G.] Boston Univ, Dept Math & Stat, Boston, MA 02215 USA. [Ellinor, Patrick T.] Massachusetts Gen Hosp, Ctr Human Genet Res, Boston, MA 02114 USA. [Ellinor, Patrick T.] Massachusetts Gen Hosp, Cardiac Arrhythmia Serv, Boston, MA 02114 USA. [Ellinor, Patrick T.] Harvard Univ, Sch Med, Boston, MA USA. [Benjamin, Emelia J.] Boston Univ, Sch Med, Dept Med, Sect Prevent Med, Boston, MA 02118 USA. [Benjamin, Emelia J.] Boston Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA USA. RP Lin, HH (reprint author), Boston Univ, Sch Med, Dept Med, Sect Computat Biomed, Boston, MA 02215 USA. EM hhlin@bu.edu OI Lin, Honghuang/0000-0003-3043-3942; Benjamin, Emelia/0000-0003-4076-2336 FU NIH [R01HL092577, R01HL104156, K24HL105780, KL2RR031981]; American Heart Association Awards [13EIA14220013, 09FTF2190028]; Intramural Research Program of National Heart, Lung, and Blood Institute (Levy); National Heart, Lung, and Blood Institute [N01-HC-25195, 6R01-NS 17950] FX This work is supported by NIH grants R01HL092577 (Ellinor and Benjamin), R01HL104156, K24HL105780 (Ellinor), KL2RR031981 (McManus), American Heart Association Awards 13EIA14220013 (Ellinor) and 09FTF2190028 (Magnani), and the Intramural Research Program of National Heart, Lung, and Blood Institute (Levy). The Framingham Heart Study is supported by National Heart, Lung, and Blood Institute contract N01-HC-25195 and 6R01-NS 17950. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 54 TC 5 Z9 6 U1 0 U2 5 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA SN 1932-6203 J9 PLOS ONE JI PLoS One PD MAY 7 PY 2014 VL 9 IS 5 AR e96794 DI 10.1371/journal.pone.0096794 PG 7 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA AG9HB UT WOS:000335728900097 PM 24805109 ER PT J AU Szu, SC Lin, KFY Hunt, S Chu, C Thinh, D AF Szu, Shousun C. Lin, Kimi F. -Y. Hunt, Steven Chu, Chiayung Nguyen Duc Thinh TI Phase I clinical trial of O-acetylated pectin conjugate, a plant polysaccharide based typhoid vaccine SO VACCINE LA English DT Article DE Phase I pectin-based; Typhoid conjugate vaccine; Safety immunogenicity; Plant polysaccharide; Semi-synthetic ID VI-CAPSULAR POLYSACCHARIDE; 2-TO 4-YEAR-OLD CHILDREN; IGG ANTI-VI; IMMUNOLOGICAL-PROPERTIES; SALMONELLA-TYPHI; FEVER; ACID; DISEASES; VIETNAM; ADULTS AB Background: Typhoid fever remains an important cause of morbidity and mortality in the developing countries. Vi capsular polysaccharide conjugate vaccine demonstrated safety and efficacy in young children in high endemic regions. A novel typhoid conjugate vaccine based on plant polysaccharide pectin was studied in a phase I trial. Methods: Fruit pectin, having the same carbohydrate backbone structure as Vi, was purified from citrus peel and used as the polysaccharide source to prepare a semi-synthetic typhoid conjugate vaccine. Pectin was chemically O-acetylated (OAcPec) to antigenically resemble Vi and conjugated to carrier protein rEPA, a recombinant exoprotein A from Pseudomonas aeruginosa. 25 healthy volunteers, 18-45 years old, were injected once with OAcPec-rEPA. Safety and IgG antibodies reactive with Vi and pectin were analyzed. Results: No vaccine associated serious adverse reaction was reported. Six weeks after the injection of OAcPec-rEPA, 64% of the volunteers elicited >4-fold rise of anti-Vi IgG. At 26 weeks the level declined, but the difference between the levels at 6 and 26 weeks are not statistically significant. There is a direct correlation between the level of anti-Vi IgG before and after the injection (R-2 = 0.96). The anti-Vi IgG can be absorbed by Vi, but not by pectin. There was no corresponding increase of anti-pectin after the injection, indicating the antibody response to OAcPec-rEPA was specific to Vi. There is no Vi-rEPA data in US adults for comparison of immune responses. The OAcPec-rEPA elicited significantly less IgG anti-Vi in US adults than those by Vi-rEPA in Vietnamese adults. Conclusion: The O-acetylated pectin conjugate, a plant based typhoid vaccine, is safe and immunogenic in adult volunteers. Published by Elsevier Ltd. C1 [Szu, Shousun C.; Lin, Kimi F. -Y.; Hunt, Steven; Chu, Chiayung] NICHHD, NIH, Bethesda, MD 20892 USA. [Nguyen Duc Thinh] Dept Agr, Div Food Safety, Ho Chi Ming City, Vietnam. RP Szu, SC (reprint author), NICHHD, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA. EM Szus@mail.nih.gov OI Hunt, Steven/0000-0003-3533-0627 FU Intramural Research; Eunice Kennedy Shriver National Institute of Child Health & Human Development; National Institutes of Health FX The project was supported by the Intramural Research, Eunice Kennedy Shriver National Institute of Child Health & Human Development, National Institutes of Health. The authors thank The Pharmacy Development Section, Clinical Center, NIH for preparation of the final container, Ms. Dolores Bryla for administrative assistance in enrollment, Dr. Jianping Li for technical assistance in analysis, Dr. Zuzana Kossaczka for pre-clinical development, and Drs. John B. Robbins for helpful discussions. NR 36 TC 5 Z9 5 U1 1 U2 10 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0264-410X EI 1873-2518 J9 VACCINE JI Vaccine PD MAY 7 PY 2014 VL 32 IS 22 BP 2618 EP 2622 DI 10.1016/j.vaccine.2014.03.023 PG 5 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA AH4RI UT WOS:000336115300016 PM 24657719 ER PT J AU DeBuysscher, BL Scott, D Marzi, A Prescott, J Feldmann, H AF DeBuysscher, Blair L. Scott, Dana Marzi, Andrea Prescott, Joseph Feldmann, Heinz TI Single-dose live-attenuated Nipah virus vaccines confer complete protection by eliciting antibodies directed against surface glycoproteins SO VACCINE LA English DT Article DE Nipah virus; Vaccines; Recombinant vesicular stomatitis virus; Humoral immune responses; Neutralizing antibodies; Serum transfer ID VESICULAR STOMATITIS-VIRUS; LONG-TERM PROTECTION; T-CELL RESPONSES; SUBUNIT VACCINE; HAMSTER MODEL; NEUTRALIZING ANTIBODIES; HENIPAVIRUS INFECTION; CLINICAL-FEATURES; VIRAL ENTRY; IN-VIVO AB Background: Nipah virus (NiV), a zoonotic pathogen causing severe respiratory illness and encephalitis in humans, emerged in Malaysia in 1998 with subsequent outbreaks on an almost annual basis since 2001 in parts of the Indian subcontinent. The high case fatality rate, human-to-human transmission, wide-ranging reservoir distribution and lack of licensed intervention options are making NiV a serious regional and potential global public health problem. The objective of this study was to develop a fast-acting, single-dose NiV vaccine that could be implemented in a ring vaccination approach during outbreaks. Methods: In this study we have designed new live-attenuated vaccine vectors based on recombinant vesicular stomatitis viruses (rVSV) expressing NiV glycoproteins (G or F) or nucleoprotein (N) and evaluated their protective efficacy in Syrian hamsters, an established NiV animal disease model. We further characterized the humoral immune response to vaccination in hamsters using ELISA and neutralization assays and performed serum transfer studies. Results: Vaccination of Syrian hamsters with a single dose of the rVSV vaccine vectors resulted in strong humoral immune responses with neutralizing activities found only in those animals vaccinated with rVSV expressing NiV G or F proteins. Vaccinated animals with neutralizing antibody responses were completely protected from lethal NiV disease, whereas animals vaccinated with rVSV expressing NiV N showed only partial protection. Protection of NiV G or F vaccinated animals was conferred by antibodies, most likely the neutralizing fraction, as demonstrated by serum transfer studies. Protection of N-vaccinated hamsters was not antibody-dependent indicating a role of adaptive cellular responses for protection. Conclusions: The rVSV vectors expressing Nipah virus G or F are prime candidates for new 'emergency vaccines' to be utilized for NiV outbreak management. Published by Elsevier Ltd. C1 [DeBuysscher, Blair L.; Marzi, Andrea; Prescott, Joseph; Feldmann, Heinz] NIAID, Virol Lab, Div Intramural Res, NIH,Rocky Mt Labs, Hamilton, MT 59840 USA. [DeBuysscher, Blair L.] Univ Montana, Div Biol Sci, Missoula, MT 59812 USA. [Scott, Dana] NIAID, Rocky Mt Vet Branch, Div Intramural Res, NIH,Rocky Mt Labs, Hamilton, MT USA. RP Feldmann, H (reprint author), NIAID, Virol Lab, Div Intramural Res, NIH,Rocky Mt Labs, Hamilton, MT 59840 USA. EM feldmannh@niaid.nih.gov FU Division of Intramural Research (DIR); National Institutes of Allergy and Infection Diseases (NIAID); National Institutes of Health (NIH) FX This work was supported by the Division of Intramural Research (DIR), National Institutes of Allergy and Infection Diseases (NIAID), National Institutes of Health (NIH). The authors would like to thank Dan Long, Rebecca Rosenke, and Tina Thomas (Rocky Mountain Veterinary Branch, DIR, NIAID, NIH) for histopathology work, Elaine Haddock (DIR, NIAID, NIH) for BSL4 technical assistance and Anita Mora (DIR, NIAID, NIH) for graphics. NR 52 TC 6 Z9 6 U1 1 U2 13 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0264-410X EI 1873-2518 J9 VACCINE JI Vaccine PD MAY 7 PY 2014 VL 32 IS 22 BP 2637 EP 2644 DI 10.1016/j.vaccine.2014.02.087 PG 8 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA AH4RI UT WOS:000336115300019 PM 24631094 ER PT J AU Insel, TR AF Insel, Thomas R. TI Mental Disorders in Childhood Shifting the Focus From Behavioral Symptoms to Neurodevelopmental Trajectories SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Editorial Material ID PSYCHOSIS; BURDEN C1 NIMH, NIH, Bethesda, MD 20892 USA. RP Insel, TR (reprint author), NIMH, NIH, NIMH Room 8129,6001 Execut Blvd, Bethesda, MD 20892 USA. EM insel@mail.nih.gov NR 10 TC 26 Z9 26 U1 2 U2 9 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 MAY 7 PY 2014 VL 311 IS 17 BP 1727 EP 1728 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA AG4IG UT WOS:000335382300011 PM 24794359 ER PT J AU Batshaw, ML Groft, SC Krischer, JP AF Batshaw, Mark L. Groft, Stephen C. Krischer, Jeffrey P. TI Research Into Rare Diseases of Childhood SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Editorial Material ID CHILDREN C1 [Batshaw, Mark L.] Childrens Natl Med Ctr, Washington, DC 20010 USA. [Groft, Stephen C.] NIH, Off Rare Dis Res, Natl Ctr Adv Translat Sci, Bethesda, MD 20892 USA. [Krischer, Jeffrey P.] Univ S Florida, Pediat Epidemiol Ctr, Tampa, FL USA. RP Batshaw, ML (reprint author), Childrens Natl Med Ctr, 111 Michigan Ave NW, Washington, DC 20010 USA. EM mbatshaw@childrensnational.org NR 7 TC 10 Z9 11 U1 0 U2 3 PU AMER MEDICAL ASSOC PI CHICAGO PA 330 N WABASH AVE, STE 39300, CHICAGO, IL 60611-5885 USA SN 0098-7484 EI 1538-3598 J9 JAMA-J AM MED ASSOC JI JAMA-J. Am. Med. Assoc. PD MAY 7 PY 2014 VL 311 IS 17 BP 1729 EP 1730 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA AG4IG UT WOS:000335382300012 PM 24794360 ER PT J AU Bezerra, JA Spino, C Magee, JC Shneider, BL Rosenthal, P Wang, KS Erlichman, J Haber, B Hertel, PM Karpen, SJ Kerkar, N Loomes, KM Molleston, JP Murray, KF Romero, R Schwarz, KB Shepherd, R Suchy, FJ Turmelle, YP Whitington, PF Moore, J Sherker, AH Robuck, PR Sokol, RJ AF Bezerra, Jorge A. Spino, Cathie Magee, John C. Shneider, Benjamin L. Rosenthal, Philip Wang, Kasper S. Erlichman, Jessi Haber, Barbara Hertel, Paula M. Karpen, Saul J. Kerkar, Nanda Loomes, Kathleen M. Molleston, Jean P. Murray, Karen F. Romero, Rene Schwarz, Kathleen B. Shepherd, Ross Suchy, Frederick J. Turmelle, Yumirle P. Whitington, Peter F. Moore, Jeffrey Sherker, Averell H. Robuck, Patricia R. Sokol, Ronald J. CA ChiLDREN TI Use of Corticosteroids After Hepatoportoenterostomy for Bile Drainage in Infants With Biliary Atresia The START Randomized Clinical Trial SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Article ID ADJUVANT STEROID-THERAPY; KASAI PORTOENTEROSTOMY; OUTCOMES; MANAGEMENT; IMPROVE; FLOW AB IMPORTANCE Biliary atresia is the most common cause of end-stage liver disease in children. Controversy exists as to whether use of steroids after hepatoportoenterostomy improves clinical outcome. OBJECTIVE To determine whether the addition of high-dose corticosteroids after hepatoportoenterostomy is superior to surgery alone in improving biliary drainage and survival with the native liver. DESIGN, SETTING, AND PATIENTS The multicenter, double-blind Steroids in Biliary Atresia Randomized Trial (START) was conducted in 140 infants (mean age, 2.3 months) between September 2005 and February 2011 in the United States; follow-up ended in January 2013. INTERVENTIONS Participants were randomized to receive intravenous methylprednisolone (4 mg/kg/d for 2 weeks) and oral prednisolone (2 mg/kg/d for 2 weeks) followed by a tapering protocol for 9 weeks (n = 70) or placebo (n = 70) initiated within 72 hours of hepatoportoenterostomy. MAIN OUTCOMES AND MEASURES The primary end point (powered to detect a 25% absolute treatment difference) was the percentage of participants with a serum total bilirubin level of less than 1.5 mg/dL with his/her native liver at 6 months posthepatoportoenterostomy. Secondary outcomes included survival with native liver at 24 months of age and serious adverse events. RESULTS The proportion of participants with improved bile drainage was not statistically significantly improved by steroids at 6 months posthepatoportoenterostomy (58.6%[41/70] of steroids group vs 48.6%[34/70] of placebo group; adjusted relative risk, 1.14 [95% CI, 0.83 to 1.57]; P =.43). The adjusted absolute risk difference was 8.7%(95% CI, -10.4% to 27.7%). Transplant-free survival was 58.7% in the steroids group vs 59.4% in the placebo group (adjusted hazard ratio, 1.0 [95% CI, 0.6 to 1.8]; P = .99) at 24 months of age. The percentage of participants with serious adverse events was 81.4%[57/70] of the steroids group and 80.0%[56/70] of the placebo group (P > .99); however, participants receiving steroids had an earlier time of onset of their first serious adverse event by 30 days posthepatoportoenterostomy (37.2%[95% CI, 26.9% to 50.0%] of steroids group vs 19.0% [95% CI, 11.5% to 30.4%] of placebo group; P = .008). CONCLUSIONS AND RELEVANCE Among infants with biliary atresia who have undergone hepatoportoenterostomy, high-dose steroid therapy following surgery did not result in statistically significant treatment differences in bile drainage at 6 months, although a small clinical benefit could not be excluded. Steroid treatment was associated with earlier onset of serious adverse events in children with biliary atresia. C1 [Bezerra, Jorge A.] Cincinnati Childrens Hosp Med Ctr, Cincinnati, OH 45229 USA. [Spino, Cathie; Magee, John C.; Moore, Jeffrey] Univ Michigan, Ann Arbor, MI 48109 USA. [Shneider, Benjamin L.] UPMC, Childrens Hosp Pittsburgh, Pittsburgh, PA USA. [Rosenthal, Philip] UCSF Benioff Childrens Hosp, San Francisco, CA USA. [Wang, Kasper S.] Childrens Hosp Los Angeles, Los Angeles, CA 90027 USA. [Wang, Kasper S.] Univ So Calif, Los Angeles, CA USA. [Erlichman, Jessi; Haber, Barbara; Loomes, Kathleen M.] Childrens Hosp Philadelphia, Philadelphia, PA 19104 USA. [Hertel, Paula M.; Shepherd, Ross] Baylor Coll Med, Houston, TX 77030 USA. [Hertel, Paula M.; Shepherd, Ross] Texas Childrens Hosp, Houston, TX 77030 USA. [Karpen, Saul J.; Romero, Rene] Emory Univ, Sch Med, Atlanta, GA USA. [Karpen, Saul J.; Romero, Rene] Childrens Healthcare Atlanta, Atlanta, GA USA. [Kerkar, Nanda] Mt Sinai Sch Med, New York, NY USA. [Molleston, Jean P.] Indiana Univ Sch Med, Indianapolis, IN 46202 USA. [Molleston, Jean P.] Riley Hosp Children, Indianapolis, IN USA. [Murray, Karen F.] Seattle Childrens Hosp, Seattle, WA USA. [Schwarz, Kathleen B.] Johns Hopkins Univ, Sch Med, Baltimore, MD USA. [Suchy, Frederick J.; Sokol, Ronald J.] Univ Colorado, Sch Med, Aurora, CO USA. [Suchy, Frederick J.; Sokol, Ronald J.] Childrens Hosp Colorado, Aurora, CO USA. [Turmelle, Yumirle P.] Washington Univ, Sch Med, St Louis, MO USA. [Whitington, Peter F.] Lurie Childrens Hosp Chicago, Chicago, IL USA. [Sherker, Averell H.; Robuck, Patricia R.] NIDDK, NIH, Bethesda, MD 20892 USA. RP Bezerra, JA (reprint author), Cincinnati Childrens Hosp Med Ctr, 3333 Burnet Ave, Cincinnati, OH 45229 USA. EM jorge.bezerra@cchmc.org FU National Institute of Diabetes, Digestive and Kidney Diseases (NIDDK) [DK62503, TR000424, DK62436, TR000150, DK62497, TR000077, DK62453, TR000154, DK62445, DK62481, TR000003, DK62466, TR000005, DK62500, TR000004, DK62452, TR000448, DK62470, DK84575, TR000423, DK84585, TR000454, DK84536, TR000007, DK62456]; NIDDK; GlaxoSmithKline; Axcan Pharma US Inc FX The following National Institute of Diabetes, Digestive and Kidney Diseases (NIDDK) grants supported the START study: DK62503 and TR000424 (awarded to Johns Hopkins University School of Medicine), DK62436 and TR000150 (Lurie Children's Hospital of Chicago), DK62497 and TR000077 (Cincinnati Children's Hospital Medical Center), DK62453 and TR000154 (University of Colorado School of Medicine and Children's Hospital Colorado, Aurora), DK62445 (Mount Sinai School of Medicine), DK62481 and TR000003 (Children's Hospital of Philadelphia), DK62466 and TR000005 (Children's Hospital of Pittsburgh of UPMC), DK62500 and TR000004 (UCSF Benioff Children's Hospital), DK62452 and TR000448 (Washington University School of Medicine and St Louis Children's Hospital), DK62470 (Baylor College of Medicine and Texas Children's Hospital, Houston), DK84575 and TR000423 (Seattle Children's Hospital), DK84538 and TR000130 (Children's Hospital Los Angeles and University of Southern California), DK84585, DK62470, and TR000454 (Emory University School of Medicine and Children's Healthcare of Atlanta), DK84536 and TR000007 (Indiana University School of Medicine and Riley Hospital for Children), and DK62456 (University of Michigan data coordinating center). The following companies provided support for the START study, each of which provided formula or medications as part of a cooperative agreement with the NIDDK: GlaxoSmithKline supplied ranitidine; Axcan Pharma US Inc, fat-soluble vitamins and tocopherol polyethylene glycol succinate; Axcan Pharma US Inc, ursodiol until 2009; and Mead Johnson Nutrition, Pregestimil. NR 27 TC 25 Z9 30 U1 2 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 MAY 7 PY 2014 VL 311 IS 17 BP 1750 EP 1759 DI 10.1001/jama.2014.2623 PG 10 WC Medicine, General & Internal SC General & Internal Medicine GA AG4IG UT WOS:000335382300020 PM 24794368 ER PT J AU Dabelea, D Mayer-Davis, EJ Saydah, S Imperatore, G Linder, B Divers, J Bell, R Badaru, A Talton, JW Crume, T Liese, AD Merchant, AT Lawrence, JM Reynolds, K Dolan, L Liu, LL Hamman, RF AF Dabelea, Dana Mayer-Davis, Elizabeth J. Saydah, Sharon Imperatore, Giuseppina Linder, Barbara Divers, Jasmin Bell, Ronny Badaru, Angela Talton, Jennifer W. Crume, Tessa Liese, Angela D. Merchant, Anwar T. Lawrence, Jean M. Reynolds, Kristi Dolan, Lawrence Liu, Lenna L. Hamman, Richard F. CA SEARCH Diabet Youth Study TI Prevalence of Type 1 and Type 2 Diabetes Among Children and Adolescents From 2001 to 2009 SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Article ID CHILDHOOD TYPE-1; UNITED-STATES; INCREASING INCIDENCE; RISK-FACTORS; US YOUTH; MELLITUS; SEARCH; POPULATION; OBESITY; COHORT AB IMPORTANCE Despite concern about an "epidemic," there are limited data on trends in prevalence of either type 1 or type 2 diabetes across US race and ethnic groups. OBJECTIVE To estimate changes in the prevalence of type 1 and type 2 diabetes in US youth, by sex, age, and race/ethnicity between 2001 and 2009. DESIGN, SETTING, AND PARTICIPANTS Case patients were ascertained in 4 geographic areas and 1 managed health care plan. The study population was determined by the 2001 and 2009 bridged-race intercensal population estimates for geographic sites and membership counts for the health plan. MAIN OUTCOMES AND MEASURES Prevalence (per 1000) of physician-diagnosed type 1 diabetes in youth aged 0 through 19 years and type 2 diabetes in youth aged 10 through 19 years. RESULTS In 2001, 4958 of 3.3 million youth were diagnosed with type 1 diabetes for a prevalence of 1.48 per 1000 (95% CI, 1.44-1.52). In 2009, 6666 of 3.4 million youth were diagnosed with type 1 diabetes for a prevalence of 1.93 per 1000 (95% CI, 1.88-1.97). In 2009, the highest prevalence of type 1 diabetes was 2.55 per 1000 among white youth (95% CI, 2.48-2.62) and the lowest was 0.35 per 1000 in American Indian youth (95% CI, 0.26-0.47) and type 1 diabetes increased between 2001 and 2009 in all sex, age, and race/ethnic subgroups except for those with the lowest prevalence (age 0-4 years and American Indians). Adjusted for completeness of ascertainment, there was a 21.1% (95% CI, 15.6%-27.0%) increase in type 1 diabetes over 8 years. In 2001, 588 of 1.7 million youth were diagnosed with type 2 diabetes for a prevalence of 0.34 per 1000 (95% CI, 0.31-0.37). In 2009, 819 of 1.8 million were diagnosed with type 2 diabetes for a prevalence of 0.46 per 1000 (95% CI, 0.43-0.49). In 2009, the prevalence of type 2 diabetes was 1.20 per 1000 among American Indian youth (95% CI, 0.96-1.51); 1.06 per 1000 among black youth (95% CI, 0.93-1.22); 0.79 per 1000 among Hispanic youth (95% CI, 0.70-0.88); and 0.17 per 1000 among white youth (95% CI, 0.15-0.20). Significant increases occurred between 2001 and 2009 in both sexes, all age-groups, and in white, Hispanic, and black youth, with no significant changes for Asian Pacific Islanders and American Indians. Adjusted for completeness of ascertainment, there was a 30.5%(95% CI, 17.3%-45.1%) overall increase in type 2 diabetes. CONCLUSIONS AND RELEVANCE Between 2001 and 2009 in 5 areas of the United States, the prevalence of both type 1 and type 2 diabetes among children and adolescents increased. Further studies are required to determine the causes of these increases. C1 [Dabelea, Dana; Crume, Tessa; Hamman, Richard F.] Colorado Sch Publ Hlth, Dept Epidemiol, Aurora, CO 80045 USA. [Mayer-Davis, Elizabeth J.] Univ N Carolina, Dept Nutr, Chapel Hill, NC USA. [Saydah, Sharon; Imperatore, Giuseppina] Ctr Dis Control & Prevent, Div Diabet Translat, Atlanta, GA USA. [Linder, Barbara] NIDDK, Childhood Diabet Res Div Diabet Endocrinol & Meta, Bethesda, MD 20892 USA. [Divers, Jasmin; Talton, Jennifer W.] Wake Forest Sch Med, Dept Biostat Sci, Winston Salem, NC USA. [Bell, Ronny] Wake Forest Sch Med, Dept Epidemiol & Prevent, Winston Salem, NC USA. [Badaru, Angela] Childrens Hosp & Reg Med Ctr, Dept Pediat Endocrinol & Diabet, Seattle, WA USA. [Liese, Angela D.; Merchant, Anwar T.] Arnold Sch Publ Hlth, Dept Epidemiol & Biostat, Columbia, SC USA. [Lawrence, Jean M.; Reynolds, Kristi] Kaiser Permanente So Calif, Dept Res & Evaluat, Pasadena, CA 91101 USA. [Dolan, Lawrence] Childrens Hosp Med Ctr, Dept Endocrinol, Cincinnati, OH USA. [Liu, Lenna L.] Univ Washington, Dept Pediat, Seattle, WA 98195 USA. [Liu, Lenna L.] Seattle Childrens Hosp, Seattle, WA USA. RP Dabelea, D (reprint author), Colorado Sch Publ Hlth, Dept Epidemiol, 13001 East 17th Pl,Campus Box B-119, Aurora, CO 80045 USA. EM dana.dabelea@ucdenver.edu FU CDC [PA00097, DP-05-069, DP-10-001]; National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK); NIDDK; National Institutes of Health (NIH) National Center for Research Resources [UL1RR029882]; NIH [UL1 TR00423]; Clinical and Translational Research Center [UL1 TR000154]; Diabetes and Endocrinology Research Center, NIH [P30 DK57516]; National Center for Research Resources [8 UL1 TR000077]; National Center for Advancing Translational Sciences, NIH; Children with Medical Handicaps program; [U48/CCU919219]; [U01 DP000246]; [U18DP002714]; [U48/CCU819241-3]; [U01 DP000247]; [U18DP000247-06A1]; [U48/CCU519239]; [U01 DP000248]; [1U18DP002709]; [U48/CCU419249]; [U01 DP000254]; [U18DP002708-01]; [U58/CCU019235-4]; [U01 DP000244]; [U18DP002710-01]; [U01 DP000250]; [200-2010-35171] FX SEARCH for Diabetes in Youth is funded by grants PA00097, DP-05-069, and DP-10-001 from the CDC and by the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK). Additional funding was provided to the CDC for these cooperative agreements by the NIDDK. The site contracts grants are U48/CCU919219, U01 DP000246, and U18DP002714 to Kaiser Permanente Southern California; U48/CCU819241-3, U01 DP000247, and U18DP000247-06A1 to the University of Colorado Denver; U48/CCU519239, U01 DP000248, and 1U18DP002709 to the Children's Hospital Medical Center, Cincinnati, Ohio; U48/CCU419249, U01 DP000254, and U18DP002708-01 to the University of North Carolina at Chapel Hill; U58/CCU019235-4, U01 DP000244, and U18DP002710-01 to the University of Washington School of Medicine; U48/CCU919219, U01 DP000250, and 200-2010-35171 to the Wake Forest University School of Medicine. This project was also support by grants UL1RR029882 from the National Institutes of Health (NIH) National Center for Research Resources to the South Carolina Clinical & Translational Research [SCTR] Institute, at the Medical University of South Carolina; UL1 TR00423 from the NIH Clinical and Translational Science Award to the Seattle Children's Hospital of the University of Washington; UL1 TR000154 from the Clinical and Translational Research Center to the University of Colorado Pediatric Clinical; P30 DK57516 from the Diabetes and Endocrinology Research Center, NIH, to the Barbara Davis Center at the University of Colorado at Denver; 8 UL1 TR000077 from the National Center for Research Resources and the National Center for Advancing Translational Sciences, NIH; and the Children with Medical Handicaps program managed by the Ohio Department of Health. NR 43 TC 232 Z9 233 U1 5 U2 63 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 MAY 7 PY 2014 VL 311 IS 17 BP 1778 EP 1786 DI 10.1001/jama.2014.3201 PG 9 WC Medicine, General & Internal SC General & Internal Medicine GA AG4IG UT WOS:000335382300023 PM 24794371 ER PT J AU Yanovski, SZ Yanovski, JA AF Yanovski, Susan Z. Yanovski, Jack A. TI Drugs for the Treatment of Obesity Reply SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Letter C1 [Yanovski, Susan Z.] NIDDK, Div Digest Dis & Nutr, Bethesda, MD 20892 USA. [Yanovski, Jack A.] NICHHD, Sect Growth & Obes, Bethesda, MD 20892 USA. RP Yanovski, SZ (reprint author), NIDDK, 6707 Democracy Blvd, Bethesda, MD 20892 USA. EM sy29f@nih.gov OI Yanovski, Jack/0000-0001-8542-1637 NR 0 TC 0 Z9 0 U1 0 U2 2 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 MAY 7 PY 2014 VL 311 IS 17 BP 1807 EP 1807 PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA AG4IG UT WOS:000335382300030 PM 24794379 ER PT J AU Tunnicliffe, EM Scott, AD Ferreira, P Ariga, R McGill, LA Nielles-Vallespin, S Neubauer, S Pennell, DJ Robson, MD Firmin, DN AF Tunnicliffe, Elizabeth M. Scott, Andrew D. Ferreira, Pedro Ariga, Rina McGill, Laura-Ann Nielles-Vallespin, Sonia Neubauer, Stefan Pennell, Dudley J. Robson, Matthew D. Firmin, David N. TI Intercentre reproducibility of cardiac apparent diffusion coefficient and fractional anisotropy in healthy volunteers SO JOURNAL OF CARDIOVASCULAR MAGNETIC RESONANCE LA English DT Article DE Cardiovascular magnetic resonance; Cardiac diffusion tensor imaging; Cardiac diffusion weighted imaging ID IN-VIVO; MAGNETIC-RESONANCE; FIBER ARCHITECTURE; TENSOR MRI; SPIN ECHOES; HUMAN HEART; MOTION; NOISE; INFARCTION; WATER AB Background: Diffusion tensor cardiac magnetic resonance (DT-CMR) enables probing of the microarchitecture of the myocardium, but the apparent diffusion coefficient (ADC) and fractional anisotropy (FA) reported in healthy volunteers have been inconsistent. The aim of this study was to validate a stimulated-echo diffusion sequence using phantoms, and to assess the intercentre reproducibility of in-vivo diffusion measures using the sequence. Methods and results: A stimulated-echo, cardiac-gated DT-CMR sequence with a reduced-field-of-view, single-shot EPI readout was used at two centres with 3 T MRI scanners. Four alkane phantoms with known diffusivities were scanned at a single centre using a stimulated echo sequence and a spin-echo Stejskal-Tanner diffusion sequence. The median (maximum, minimum) difference between the DT-CMR sequence and Stejskal-Tanner sequence was 0.01 (0.04, 0.0006) x 10(-3) mm(2)/s (2%), and between the DT-CMR sequence and literature diffusivities was 0.02 (0.05, 0.006) x 10-3 mm2/s (4%). The same ten healthy volunteers were scanned using the DT-CMR sequence at the two centres less than seven days apart. Average ADC and FA were calculated in a single mid-ventricular, short axis slice. Intercentre differences were tested for statistical significance at the p < 0.05 level using paired t-tests. The mean DC standard deviation for all subjects averaged over both centres was 1.10 +/- 0.06 x 10(-3) mm(2)/s in systole and 1.20 +/- 0.09 x 10(-3) mm(2)/s in diastole; FA was 0.41 +/- 0.04 in systole and 0.54 +/- 0.03 in diastole. With similarly-drawn regions-of-interest, systolic ADC (difference 0.05 x 10(-3) mm(2)/s), systolic FA (difference 0.003) and diastolic FA (difference 0.01) were not statistically significantly different between centres (p > 0.05), and only the diastolic ADC showed a statistically significant, but numerically small, difference of 0.07 x 10(-3) mm(2)/s (p = 0.047). The intercentre, intrasubject coefficients of variance were: systolic ADC 7%, FA 6%; diastolic ADC 7%, FA 3%. Conclusions: This is the first study to demonstrate the accuracy of a stimulated-echo DT-CMR sequence in phantoms, and demonstrates the feasibility of obtaining reproducible ADC and FA in healthy volunteers at separate centres with well-matched sequences and processing. C1 [Tunnicliffe, Elizabeth M.; Ariga, Rina; Neubauer, Stefan; Robson, Matthew D.] Univ Oxford, Radcliffe Dept Med, Div Cardiovasc Med, Oxford Ctr Clin Magnet Resonance Res, Oxford, England. [Scott, Andrew D.; Ferreira, Pedro; McGill, Laura-Ann; Nielles-Vallespin, Sonia; Pennell, Dudley J.; Firmin, David N.] Royal Brompton Hosp, NIHR Cardiovasc BRU, London SW3 6LY, England. [Scott, Andrew D.; Ferreira, Pedro; McGill, Laura-Ann; Nielles-Vallespin, Sonia; Pennell, Dudley J.; Firmin, David N.] Univ London Imperial Coll Sci Technol & Med, London, England. [Nielles-Vallespin, Sonia] NHLBI, NIH, DHHS, Bethesda, MD 20892 USA. RP Tunnicliffe, EM (reprint author), Univ Oxford, Radcliffe Dept Med, Div Cardiovasc Med, Oxford Ctr Clin Magnet Resonance Res, Oxford, England. EM elizabeth.tunnicliffe@cardiov.ox.ac.uk FU National Institute for Health Research (NIHR) Oxford Biomedical Research Centre (BRC) based at The Oxford University Hospitals Trust at the University of Oxford; NIHR Cardiovascular Biomedical Research Unit at Royal Brompton Hospital and Imperial College, London FX This work was supported by the National Institute for Health Research (NIHR) Oxford Biomedical Research Centre (BRC) based at The Oxford University Hospitals Trust at the University of Oxford, and the NIHR Cardiovascular Biomedical Research Unit at Royal Brompton Hospital and Imperial College, London. The views expressed are those of the authors and not necessarily those of the National Health Service, the NIHR or the Department of Health. We thank Jacqueline Birks, NIHR Oxford BRC Senior Medical Statistician at the Oxford Centre for Statistics in Medicine, for helpful statistical discussion. NR 25 TC 13 Z9 13 U1 1 U2 6 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 MAY 6 PY 2014 VL 16 AR 31 DI 10.1186/1532-429X-16-31 PG 12 WC Cardiac & Cardiovascular Systems; Radiology, Nuclear Medicine & Medical Imaging SC Cardiovascular System & Cardiology; Radiology, Nuclear Medicine & Medical Imaging GA AK7EM UT WOS:000338589100001 PM 24886285 ER PT J AU McKinnon, JE Mailliard, RB Swindells, S Wilkin, TJ Borowski, L Roper, JM Bastow, B Kearney, M Wiegand, A Mellors, JW Rinaldo, CR AF McKinnon, John E. Mailliard, Robbie B. Swindells, Susan Wilkin, Timothy J. Borowski, LuAnn Roper, Jillian M. Bastow, Barbara Kearney, Mary Wiegand, Ann Mellors, John W. Rinaldo, Charles R. CA A5201 Study Team TI Baseline Natural Killer and T Cell Populations Correlation with Virologic Outcome after Regimen Simplification to Atazanavir/Ritonavir Alone (ACTG 5201) SO PLOS ONE LA English DT Article ID LOPINAVIR-RITONAVIR MONOTHERAPY; MAINTENANCE ANTIRETROVIRAL THERAPY; HIV-1 INFECTION; INDUCTION THERAPY; 2 NUCLEOSIDES; 50 COPIES/ML; NK CELLS; TRIAL; SUPPRESSION; RECEPTORS AB Objectives: Simplified maintenance therapy with ritonavir-boosted atazanavir (ATV/r) provides an alternative treatment option for HIV-1 infection that spares nucleoside analogs (NRTI) for future use and decreased toxicity. We hypothesized that the level of immune activation (IA) and recovery of lymphocyte populations could influence virologic outcomes after regimen simplification. Methods: Thirty-four participants with virologic suppression >= 48 weeks on antiretroviral therapy (2 NRTI plus protease inhibitor) were switched to ATV/r alone in the context of the ACTG 5201 clinical trial. Flow cytometric analyses were performed on PBMC isolated from 25 patients with available samples, of which 24 had lymphocyte recovery sufficient for this study. Assessments included enumeration of T-cells (CD4/CD8), natural killer (NK) (CD3(+)CD56(+)CD16(+)) cells and cell-associated markers (HLA-DR, CD's 38/69/94/95/158/279). Results: Eight of the 24 patients had at least one plasma HIV-1 RNA level (VL) > 50 copies/mL during the study. NK cell levels below the group median of 7.1% at study entry were associated with development of VL > 50 copies/mL following simplification by regression and survival analyses (p = 0.043 and 0.023), with an odds ratio of 10.3 (95% CI: 1.92-55.3). Simplification was associated with transient increases in naive and CD25(+) CD4(+) T-cells, and had no impact on IA levels. Conclusions: Lower NK cell levels prior to regimen simplification were predictive of virologic rebound after discontinuation of nucleoside analogs. Regimen simplification did not have a sustained impact on markers of IA or T lymphocyte populations in 48 weeks of clinical monitoring. C1 [McKinnon, John E.] Henry Ford Hosp Syst, Detroit, MI 48202 USA. [Mailliard, Robbie B.; Borowski, LuAnn; Mellors, John W.; Rinaldo, Charles R.] Univ Pittsburgh, Pittsburgh, PA USA. [Swindells, Susan] Univ Nebraska Med Ctr, Omaha, NE USA. [Wilkin, Timothy J.] Weill Cornell Med Coll, New York, NY USA. [Roper, Jillian M.] George Washington Univ, Washington, DC USA. [Bastow, Barbara] Social & Sci Syst Inc, Silver Spring, MD USA. [Kearney, Mary; Wiegand, Ann] NCI, HIV Drug Resistance Program, Frederick, MD 21701 USA. RP McKinnon, JE (reprint author), Henry Ford Hosp Syst, Detroit, MI 48202 USA. EM jmckinn3@hfhs.org OI Mailliard, Robbie/0000-0001-5501-503X FU NIH grants from the National Center for Research Resources (NCRR) [1KL2-RR024154-03, UL1 RR024153]; National Cancer Institute (SAIC) [2sXS119]; NIH grant from the National Institute of Allergy and Infectious Diseases [AI069450]; [1R21-AI084423-02]; [U01-AI35041]; [U01-AI068636]; [R37-AI41870] FX Financial support for this manuscript was received for JEM from NIH grants 1KL2-RR024154-03, UL1 RR024153 from the National Center for Research Resources (NCRR) and 1R21-AI084423-02. RBM has received financial support from U01-AI35041, U01-AI068636 and R37-AI41870. JWM has received financial support from the National Cancer Institute (SAIC contract 2sXS119). SS was supported by NIH grant AI069450 from the National Institute of Allergy and Infectious Diseases. CRR has received support from U01-AI35041 and U01-AI068636. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 41 TC 0 Z9 0 U1 0 U2 2 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA SN 1932-6203 J9 PLOS ONE JI PLoS One PD MAY 6 PY 2014 VL 9 IS 5 AR e95524 DI 10.1371/journal.pone.0095524 PG 9 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA AJ9KS UT WOS:000338029800030 PM 24802242 ER PT J AU Vasconcelos, AR Yshii, LM Viel, TA Buck, HS Mattson, MP Scavone, C Kawamoto, EM AF Vasconcelos, Andrea R. Yshii, Lidia M. Viel, Tania A. Buck, Hudson S. Mattson, Mark P. Scavone, Cristoforo Kawamoto, Elisa M. TI Intermittent fasting attenuates lipopolysaccharide-induced neuroinflammation and memory impairment SO JOURNAL OF NEUROINFLAMMATION LA English DT Article DE Intermittent fasting; Inflammation; TLR4; Memory ID FACTOR-KAPPA-B; TOLL-LIKE RECEPTORS; ADULT HIPPOCAMPAL NEUROGENESIS; AMYLOID BETA-PEPTIDE; ALZHEIMERS-DISEASE; NITRIC-OXIDE; CALORIC RESTRICTION; NEUROTROPHIC FACTOR; TNF-ALPHA; COGNITIVE IMPAIRMENT AB Background: Systemic bacterial infections often result in enduring cognitive impairment and are a risk factor for dementia. There are currently no effective treatments for infection-induced cognitive impairment. Previous studies have shown that intermittent fasting (IF) can increase the resistance of neurons to injury and disease by stimulating adaptive cellular stress responses. However, the impact of IF on the cognitive sequelae of systemic and brain inflammation is unknown. Methods: Rats on IF for 30 days received 1 mg/ kg of lipopolysaccharide (LPS) or saline intravenously. Half of the rats were subjected to behavioral tests and the other half were euthanized two hours after LPS administration and the hippocampus was dissected and frozen for analyses. Results: Here, we report that IF ameliorates cognitive deficits in a rat model of sepsis by a mechanism involving NF-B activation, suppression of the expression of pro-inflammatory cytokines, and enhancement of neurotrophic support. Treatment of rats with LPS resulted in deficits in cognitive performance in the Barnes maze and inhibitory avoidance tests, without changing locomotor activity, that were ameliorated in rats that had been maintained on the IF diet. IF also resulted in reduced levels of mRNAs encoding the LPS receptor TLR4 and inducible nitric oxide synthase (iNOS) in the hippocampus. Moreover, IF prevented LPS-induced elevation of IL-1 alpha, IL-1 beta and TNF-alpha levels, and prevented the LPS-induced reduction of BDNF levels in the hippocampus. IF also significantly attenuated LPS-induced elevations of serum IL-1 beta, IFN-gamma, RANTES, TNF-alpha and IL-6 levels. Conclusions: Taken together, our results suggest that IF induces adaptive responses in the brain and periphery that can suppress inflammation and preserve cognitive function in an animal model of systemic bacterial infection. C1 [Vasconcelos, Andrea R.; Yshii, Lidia M.; Scavone, Cristoforo; Kawamoto, Elisa M.] Univ Sao Paulo, Inst Biomed Sci, Dept Pharmacol, BR-05508900 Sao Paulo, Brazil. [Viel, Tania A.] Univ Sao Paulo, Sch Arts Sci & Humanities, BR-03828080 Sao Paulo, Brazil. [Buck, Hudson S.] Santa Casa Sao Paulo Med Sch, Dept Physiol Sci, BR-01221020 Sao Paulo, Brazil. [Mattson, Mark P.; Kawamoto, Elisa M.] NIA, Neurosci Lab, Intramural Res Program, Baltimore, MD 21224 USA. RP Scavone, C (reprint author), Univ Sao Paulo, Inst Biomed Sci, Dept Pharmacol, BR-05508900 Sao Paulo, Brazil. EM criscavone@usp.br RI Kawamoto, Elisa/E-3485-2012; Buck, Hudson/E-7664-2013; YSHII, Lidia/I-6039-2013 OI Kawamoto, Elisa/0000-0001-8637-414X; Buck, Hudson/0000-0002-1867-2441; Scavone, Cristoforo/0000-0002-1206-0882; YSHII, Lidia/0000-0002-1988-6855 FU Fundacao de Amparo a Pesquisa do Estado de Sao Paulo-FAPESP [2008/58865-9, 2009/11915-4, 2006/57729-9]; University of Sao Paulo [2011.1.9333.1.3]; National Institute on Aging Intramural Research Program FX We thank L Lima de Sa and D Andreotti for the technical assistance. This research was supported by grants from Fundacao de Amparo a Pesquisa do Estado de Sao Paulo-FAPESP to CS (2008/58865-9; 2009/11915-4), and to EMK (2006/57729-9). It is also partially funded by the University of Sao Paulo (Grant # 2011.1.9333.1.3, NAPNA) and the National Institute on Aging Intramural Research Program. ARV is a PhD student and research fellow from FAPESP. LMY and EMK are supported by postdoctorate fellowships from FAPESP. CS is research fellow from Conselho Nacional de Desenvolvimento Cientifico e Tecnologico-CNPq. NR 92 TC 23 Z9 24 U1 7 U2 17 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1742-2094 J9 J NEUROINFLAMM JI J. Neuroinflamm. PD MAY 6 PY 2014 VL 11 AR 85 DI 10.1186/1742-2094-11-85 PG 14 WC Immunology; Neurosciences SC Immunology; Neurosciences & Neurology GA AI9MC UT WOS:000337255700001 PM 24886300 ER PT J AU Halsey, CHC Gustafson, DL Rose, BJ Wolf-Ringwall, A Burnett, RC Duval, DL Avery, AC Thamm, DH AF Halsey, Charles H. C. Gustafson, Daniel L. Rose, Barbara J. Wolf-Ringwall, Amber Burnett, Robert C. Duval, Dawn L. Avery, Anne C. Thamm, Douglas H. TI Development of an in vitro model of acquired resistance to toceranib phosphate (Palladia (R)) in canine mast cell tumor SO BMC VETERINARY RESEARCH LA English DT Article DE Canine mast cell tumor; Toceranib; c-kit; Acquired resistance ID TYROSINE KINASE INHIBITORS; GASTROINTESTINAL STROMAL TUMORS; P-GLYCOPROTEIN; C-KIT; FACTOR-RECEPTOR; CANCER-THERAPY; IMATINIB RESISTANCE; TANDEM DUPLICATIONS; LUNG-CANCER; MDR1 GENE AB Background: Mast cell tumors (MCTs) are the most common skin tumors in dogs and exhibit variable biologic behavior. Mutations in the c-kit proto-oncogene are associated with the tumorigenesis of MCTs, resulting in growth factor-independent and constitutive phosphorylation of the KIT receptor tyrosine kinase (RTK). Toceranib (TOC) phosphate (Palladia (R)) is a KIT RTK inhibitor that has biological activity against MCTs. Despite these benefits, patients ultimately develop resistance to TOC. Therefore, there is a need to identify distinguishing clinical and molecular features of resistance in this population. Results: The canine C2 mastocytoma cell line contains an activating mutation in c-kit. Three TOC-resistant C2 sublines (TR1, TR2, TR3) were established over seven months by growing cells in increasing concentrations of TOC. TOC inhibited KIT phosphorylation and cell proliferation in a dose-dependent manner in the treatment-naive, parental C2 line (IC50 < 10 nM). In contrast, the three sublines were resistant to growth inhibition by TOC (IC50 > 1,000 nM) and phosphorylation of the KIT receptor was less inhibited compared to the TOC-sensitive C2 cells. Interestingly, sensitivity to three structurally distinct KIT RTK inhibitors was variable among the sublines, and all 3 sublines retained sensitivity to the cytotoxic agents vinblastine and lomustine. Sequencing of c-kit revealed secondary mutations in the juxtamembrane and tyrosine kinase domains of the resistant sublines. These included point mutations in TR1 (Q574R, M835T), TR2 (K724R), and TR3 (K580R, R584G, A620S). Additionally, chronic TOC exposure resulted in c-kit mRNA and KIT protein overexpression in the TOC-resistant sublines compared to the parental line. C2, TR1, TR2, and TR3 cells demonstrated minimal P-glycoprotein (P-gp) activity and no functional P-gp. Conclusions: This study demonstrates the development of an in vitro model of acquired resistance to targeted therapy in canine MCTs harboring a c-kit-activating mutation. This model may be used to investigate the molecular basis of and strategies to overcome TOC resistance. C1 [Halsey, Charles H. C.; Gustafson, Daniel L.; Duval, Dawn L.; Avery, Anne C.; Thamm, Douglas H.] Colorado State Univ, Cell & Mol Biol Program, Ft Collins, CO 80523 USA. [Halsey, Charles H. C.; Burnett, Robert C.; Avery, Anne C.] Colorado State Univ, Coll Vet Med & Biomed Sci, Dept Microbiol Immunol & Pathol, Ft Collins, CO 80523 USA. [Gustafson, Daniel L.; Rose, Barbara J.; Wolf-Ringwall, Amber; Duval, Dawn L.; Thamm, Douglas H.] Colorado State Univ, Coll Vet Med & Biomed Sci, Dept Clin Sci, Ft Collins, CO 80523 USA. [Gustafson, Daniel L.; Thamm, Douglas H.] Univ Colorado, Ctr Comprehens Canc, Aurora, CO USA. [Halsey, Charles H. C.] NCI, Lab Canc Biol & Genet, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. RP Halsey, CHC (reprint author), Colorado State Univ, Cell & Mol Biol Program, Ft Collins, CO 80523 USA. EM charles.halsey@nih.gov RI Thamm, Douglas/I-5976-2013 OI Thamm, Douglas/0000-0002-8914-7767 FU NIH [9T32OD10437-11] FX The authors would like to acknowledge Drs. Amy Trettien, Gina Michels, and Phyllis Malpas at Zoetis for their critical review of the manuscript. The authors thank Ms. Janna Yoshimoto for her technical assistance with flow cytometry. This work and CHCH were supported by NIH 9T32OD10437-11. NR 51 TC 3 Z9 3 U1 1 U2 19 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1746-6148 J9 BMC VET RES JI BMC Vet. Res. PD MAY 6 PY 2014 VL 10 AR 105 DI 10.1186/1746-6148-10-105 PG 12 WC Veterinary Sciences SC Veterinary Sciences GA AI6LU UT WOS:000336987000001 PM 24885200 ER PT J AU Westwood, AJ Beiser, A DeCarli, C Harris, TB Chen, TC He, XM Roubenoff, R Pikula, A Au, R Braverman, LE Wolf, PA Vasan, RS Seshadri, S AF Westwood, Andrew J. Beiser, Alexa DeCarli, Charles Harris, Tamara B. Chen, Tai C. He, Xue-mei Roubenoff, Ronenn Pikula, Aleksandra Au, Rhoda Braverman, Lewis E. Wolf, Philip A. Vasan, Ramachandran S. Seshadri, Sudha TI Insulin-like growth factor-1 and risk of Alzheimer dementia and brain atrophy SO NEUROLOGY LA English DT Article ID FACTOR BINDING-PROTEINS; COGNITIVE FUNCTION; IGF-I; CEREBROSPINAL-FLUID; TAU-PHOSPHORYLATION; VOLUME CHANGES; DISEASE; HORMONE; SERUM; HIPPOCAMPUS AB Objective:To relate serum insulin-like growth factor-1 (IGF-1) to risk of Alzheimer disease (AD) dementia and to brain volumes in a dementia-free community sample spanning middle and older ages.Methods:Dementia-free Framingham participants from generation 1 (n = 789, age 79 4 years, 64% women) and generation 2 (n = 2,793, age 61 9 years, 55% women; total = 3,582, age 65 +/- 11 years, 57% women) had serum IGF-1 measured in 1990-1994 and 1998-2001, respectively, and were followed prospectively for incident dementia and AD dementia. Brain MRI was obtained in stroke- and dementia-free survivors of both generations 1 (n = 186) and 2 (n = 1,867) during 1999-2005. Baseline IGF-1 was related to risk of incident dementia using Cox models and to total brain and hippocampal volumes using linear regression in multivariable models adjusted for age, sex, APOE epsilon 4, plasma homocysteine, waist-hip ratio, and physical activity.Results:Mean IGF-1 levels were 144 +/- 60 g/L in generation 1 and 114 +/- 37 g/L in generation 2. We observed 279 cases of incident dementia (230 AD dementia) over a mean follow-up of 7.4 +/- 3.1 years. Persons with IGF-1 in the lowest quartile had a 51% greater risk of AD dementia (hazard ratio = 1.51, 95% confidence interval: 1.14-2.00; p = 0.004). Among persons without dementia, higher IGF-1 levels were associated with greater total brain volumes (/SD increment in IGF-1 was 0.55 +/- 0.24, p = 0.025; and 0.26 +/- 0.06, p < 0.001, for generations 1 and 2, respectively).Conclusion:Lower serum levels of IGF-1 are associated with an increased risk of developing AD dementia and higher levels with greater brain volumes even among middle-aged community-dwelling participants free of stroke and dementia. Higher levels of IGF-1 may protect against subclinical and clinical neurodegeneration. C1 [Westwood, Andrew J.; Beiser, Alexa; Pikula, Aleksandra; Au, Rhoda; Seshadri, Sudha] Boston Univ, Sch Med, Dept Neurol, Boston, MA 02215 USA. [Vasan, Ramachandran S.] Boston Univ, Sch Med, Dept Med, Sect Preventat Med, Boston, MA 02215 USA. [Vasan, Ramachandran S.] Boston Univ, Sch Med, Dept Med, Cardiol Sect, Boston, MA 02215 USA. [Beiser, Alexa] Boston Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02215 USA. [Beiser, Alexa; Pikula, Aleksandra; Au, Rhoda; Wolf, Philip A.; Vasan, Ramachandran S.; Seshadri, Sudha] Framingham Heart Dis Epidemiol Study, Framingham, MA USA. [DeCarli, Charles] Univ Calif Davis, Sacramento, CA 95817 USA. [Harris, Tamara B.] NIA, Bethesda, MD 20892 USA. [Chen, Tai C.; He, Xue-mei; Braverman, Lewis E.] Boston Univ, Med Ctr, Sect Endocrinol Diabet & Nutr, Boston, MA 02215 USA. [Roubenoff, Ronenn] Novartis Inst Biomed Res, Cambridge, MA USA. RP Seshadri, S (reprint author), Boston Univ, Sch Med, Dept Neurol, Boston, MA 02215 USA. EM suseshad@bu.edu OI Seshadri, Sudha/0000-0001-6135-2622; Ramachandran, Vasan/0000-0001-7357-5970; Beiser, Alexa/0000-0001-8551-7778 FU Framingham Heart Study's National Heart, Lung, and Blood Institute (NHLBI) [N01-HC-25195]; NHLBI [R01 HL089590]; National Institute on Aging [R01 AG16495, AG 033040, AG08122, AG033193, AG031287, P30AG013846]; American Heart Association [11CRP4930020]; BU-CTSI NIH [UL1-TR000157] FX Supported by the Framingham Heart Study's National Heart, Lung, and Blood Institute (NHLBI) contract (N01-HC-25195) and by grants from the NHLBI (R01 HL089590), the National Institute on Aging (R01 AG16495, AG 033040, AG08122, AG033193, and AG031287, P30AG013846), and the American Heart Association (11CRP4930020). Partial support from BU-CTSI NIH grant UL1-TR000157 is also acknowledged. NR 37 TC 28 Z9 30 U1 0 U2 10 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 MAY 6 PY 2014 VL 82 IS 18 BP 1613 EP 1619 DI 10.1212/WNL.0000000000000382 PG 7 WC Clinical Neurology SC Neurosciences & Neurology GA AH9XB UT WOS:000336497400010 PM 24706014 ER PT J AU Grool, AM Geerlings, MI Sigurdsson, S Eiriksdottir, G Jonsson, PV Garcia, ME Siggeirsdottir, K Harris, TB Sigmundsson, T Gudnason, V Launer, LJ AF Grool, Anne M. Geerlings, Mirjam I. Sigurdsson, Sigurdur Eiriksdottir, Gudny Jonsson, Palmi V. Garcia, Melissa E. Siggeirsdottir, Kristin Harris, Tamara B. Sigmundsson, Thordur Gudnason, Vilmundur Launer, Lenore J. TI Structural MRI correlates of apathy symptoms in older persons without dementia AGES-Reykjavik Study SO NEUROLOGY LA English DT Article ID WHITE-MATTER HYPERINTENSITIES; MILD COGNITIVE IMPAIRMENT; GERIATRIC DEPRESSION SCALE; LATE-LIFE DEPRESSION; ALZHEIMERS-DISEASE; NEUROPSYCHIATRIC SYMPTOMS; PROGRESSION; ATROPHY; VALIDATION; WITHDRAWAL AB Objective:We aimed to investigate the relation between apathy symptoms and structural brain changes on MRI, including white matter lesions (WMLs) and atrophy, in a large cohort of older persons.Methods:Cross-sectional analyses are based on 4,354 persons without dementia (aged 76 5 years) participating in the population-based Age, Gene/Environment Susceptibility-Reykjavik Study. Apathy symptoms were assessed with 3 items from the 15-item Geriatric Depression Scale. Brain volumes and total WML volume were estimated on 1.5-tesla MRI using an automated segmentation program; regional WML load was calculated using a semiquantitative scale. Regression analyses were adjusted for age, sex, education, intracranial volume, vascular risk factors, physical activity, brain infarcts, depressive symptoms, antidepressants, and cognitive status.Results:Compared to those with <2 apathy symptoms, participants with 2 apathy symptoms (49% of the cohort) had significantly smaller gray matter volumes (mean adjusted difference -3.6 mL, 95% confidence interval [CI] -6.2 to -1.0), particularly in the frontal and temporal lobes; smaller white matter volumes (mean adjusted difference -1.9 mL, 95% CI -3.6 to -0.3), mainly in the parietal lobe; and smaller thalamus volumes. They were also more likely to have WMLs in the frontal lobe (adjusted odds ratio = 1.08, 95% CI 0.9-1.3). Excluding participants with a depression diagnosis did not change the associations.Conclusions:In this older population without dementia, apathy symptoms are associated with a more diffuse loss of both gray and white matter volumes, independent of depression. C1 [Grool, Anne M.; Geerlings, Mirjam I.] Univ Med Ctr Utrecht, Julius Ctr Hlth Sci & Primary Care, Utrecht, Netherlands. [Grool, Anne M.] Univ Med Ctr Utrecht, Dept Radiol, Utrecht, Netherlands. [Geerlings, Mirjam I.; Garcia, Melissa E.; Harris, Tamara B.; Launer, Lenore J.] NIA, Lab Epidemiol Demog & Biometry, Bethesda, MD 20892 USA. [Sigurdsson, Sigurdur; Eiriksdottir, Gudny; Jonsson, Palmi V.; Siggeirsdottir, Kristin; Gudnason, Vilmundur] Iceland Heart Assoc, Kopavogur, Iceland. [Siggeirsdottir, Kristin] Janus Rehabil, Reykjavik, Iceland. [Sigmundsson, Thordur] Landspitali Univ Hosp, Reykjavik, Iceland. [Gudnason, Vilmundur] Univ Iceland, Reykjavik, Iceland. RP Launer, LJ (reprint author), NIA, Lab Epidemiol Demog & Biometry, Bethesda, MD 20892 USA. EM LaunerL@nia.nih.gov RI Gudnason, Vilmundur/K-6885-2015 OI Gudnason, Vilmundur/0000-0001-5696-0084 FU NIH [N01-AG-12100]; National Institute on Aging Intramural Research Program; Hjartavernd (the Icelandic Heart Association); Althingi (the Icelandic Parliament) FX The AGES-Reykjavik Study is funded by NIH contract N01-AG-12100, the National Institute on Aging Intramural Research Program, Hjartavernd (the Icelandic Heart Association), and Althingi (the Icelandic Parliament). NR 39 TC 11 Z9 12 U1 4 U2 14 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 MAY 6 PY 2014 VL 82 IS 18 BP 1628 EP 1635 DI 10.1212/WNL.0000000000000378 PG 8 WC Clinical Neurology SC Neurosciences & Neurology GA AH9XB UT WOS:000336497400012 PM 24739783 ER PT J AU Roth, JA Etzioni, R Waters, TM Pettinger, M Rossouw, JE Anderson, GL Chlebowski, RT Manson, JE Hlatky, M Johnson, KC Ramsey, SD AF Roth, Joshua A. Etzioni, Ruth Waters, Teresa M. Pettinger, Mary Rossouw, Jacques E. Anderson, Garnet L. Chlebowski, Rowan T. Manson, JoAnn E. Hlatky, Mark Johnson, Karen C. Ramsey, Scott D. TI Economic Return From the Women's Health Initiative Estrogen Plus Progestin Clinical Trial SO ANNALS OF INTERNAL MEDICINE LA English DT Article ID POSTMENOPAUSAL HORMONE-THERAPY; REPLACEMENT THERAPY; SAMPLE INFORMATION; COST-EFFECTIVENESS; UNITED-STATES; FOLLOW-UP; BENEFITS; DISEASE; RISKS; PREVENTION AB Background: The findings of the Women's Health Initiative (WHI) estrogen plus progestin (E+P) trial led to a substantial reduction in use of combined hormone therapy (cHT) among postmenopausal women in the United States. The economic effect of this shift has not been evaluated relative to the trial's $260 million cost (2012 U. S. dollars). Objective: To estimate the economic return from the WHI E+P trial. Design: Decision model to simulate health outcomes for a "WHI scenario" with observed cHT use and a "no-WHI scenario" with cHT use extrapolated from the pretrial period. Data Sources: Primary analyses of WHI outcomes, peer-reviewed literature, and government sources. Target Population: Postmenopausal women in the United States, aged 50 to 79 years, who did not have a hysterectomy. Time Horizon: 2003 to 2012. Perspective: Payer. Intervention: Combined hormone therapy. Outcome Measures: Disease incidence, expenditure, quality-adjusted life-years, and net economic return. Results of Base-Case Analysis: The WHI scenario resulted in 4.3 million fewer cHT users, 126 000 fewer breast cancer cases, 76 000 fewer cardiovascular disease cases, 263 000 more fractures, 145 000 more quality-adjusted life-years, and expenditure savings of $35.2 billion. The corresponding net economic return of the trial was $37.1 billion ($140 per dollar invested in the trial) at a willingness-to-pay level of $100 000 per quality-adjusted life-year. Results of Sensitivity Analysis: The 95% CI for the net economic return of the trial was $23.1 to $51.2 billion. Limitation: No evaluation of indirect costs or outcomes beyond 2012. Conclusion: The WHI E+P trial made high-value use of public funds with a substantial return on investment. These results can contribute to discussions about the role of public funding for large, prospective trials with high potential for public health effects. C1 Fred Hutchinson Canc Res Ctr, Seattle, WA 98109 USA. Grp Hlth Cooperat Puget Sound, Grp Hlth Res Inst, Seattle, WA 98121 USA. Univ Tennessee, Ctr Hlth Sci, Memphis, TN 38163 USA. NHLBI, NIH, Bethesda, MD 20824 USA. Harbor UCLA Med Ctr, Los Angeles Biomed Res Inst, Torrance, CA 90502 USA. Brigham & Womens Hosp, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA 02215 USA. Stanford Univ, Stanford Med Sch, Stanford, CA 94305 USA. RP Ramsey, SD (reprint author), Fred Hutchinson Canc Res Ctr, Div Publ Hlth Sci, 1100 Fairview Ave North,M3-B-232, Seattle, WA 98109 USA. EM sramsey@fhcrc.org OI Anderson, Garnet/0000-0001-5087-7837 FU National Heart, Lung, and Blood Institute FX National Heart, Lung, and Blood Institute. NR 42 TC 12 Z9 12 U1 0 U2 3 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 MAY 6 PY 2014 VL 160 IS 9 BP 594 EP U128 DI 10.7326/M13-2348 PG 10 WC Medicine, General & Internal SC General & Internal Medicine GA AI0GO UT WOS:000336524400002 PM 24798522 ER PT J AU Lauer, MS AF Lauer, Michael S. TI Investing in Clinical Science: Make Way for (Not-So-Uncommon) Outliers SO ANNALS OF INTERNAL MEDICINE LA English DT Editorial Material ID RANDOMIZED CONTROLLED-TRIAL; POSTMENOPAUSAL WOMEN; ESTROGEN; DISEASE; HEART C1 [Lauer, Michael S.] NHLBI, Bethesda, MD 20892 USA. RP Lauer, MS (reprint author), NHLBI, Div Cardiovasc Sci, 6701 Rockledge Dr,Room 8128, Bethesda, MD 20892 USA. EM lauerm@nhlbi.nih.gov NR 10 TC 1 Z9 1 U1 0 U2 2 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 MAY 6 PY 2014 VL 160 IS 9 BP 651 EP 652 DI 10.7326/M14-0655 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA AI0GO UT WOS:000336524400010 PM 24798528 ER PT J AU Padayatty, SJ Levine, M AF Padayatty, Sebastian J. Levine, Mark TI Vitamin and Mineral Supplements in the Primary Prevention of Cardiovascular Disease and Cancer SO ANNALS OF INTERNAL MEDICINE LA English DT Letter ID RANDOMIZED-TRIAL C1 [Padayatty, Sebastian J.; Levine, Mark] NIDDK, NIH, Bethesda, MD 20892 USA. RP Padayatty, SJ (reprint author), NIDDK, NIH, Bethesda, MD 20892 USA. RI Padayatty, Sebastian/A-8581-2012 OI Padayatty, Sebastian/0000-0001-8758-3170 NR 5 TC 1 Z9 1 U1 0 U2 2 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 MAY 6 PY 2014 VL 160 IS 9 BP 654 EP 654 DI 10.7326/L14-5009 PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA AI0GO UT WOS:000336524400011 PM 24798530 ER PT J AU Yun, J Finkel, T AF Yun, Jeanho Finkel, Toren TI Mitohormesis SO CELL METABOLISM LA English DT Review ID MITOCHONDRIAL CALCIUM UNIPORTER; HYPOXIA-INDUCED TRANSCRIPTION; ELEGANS LIFE-SPAN; C. ELEGANS; OXIDATIVE STRESS; GENE-EXPRESSION; CAENORHABDITIS-ELEGANS; SIGNAL-TRANSDUCTION; CELL-PROLIFERATION; ELECTRON-TRANSPORT AB For many years, mitochondria were viewed as semiautonomous organelles, required only for cellular energetics. This view has been largely supplanted by the concept that mitochondria are fully integrated into the cell and that mitochondrial stresses rapidly activate cytosolic signaling pathways that ultimately alter nuclear gene expression. Remarkably, this coordinated response to mild mitochondrial stress appears to leave the cell less susceptible to subsequent perturbations. This response, termed mitohormesis, is being rapidly dissected in many model organisms. A fuller understanding of mitohormesis promises to provide insight into our susceptibility for disease and potentially provide a unifying hypothesis for why we age. C1 [Yun, Jeanho; Finkel, Toren] NHLBI, Ctr Mol Med, NIH, Bethesda, MD 20892 USA. [Yun, Jeanho] Dong A Univ, Dept Biochem, Pusan 602714, South Korea. [Yun, Jeanho] Dong A Univ, Coll Med, Mitochondria Hub Regulat Ctr, Pusan 602714, South Korea. RP Finkel, T (reprint author), NHLBI, Ctr Mol Med, NIH, Bldg 10, Bethesda, MD 20892 USA. EM finkelt@nih.gov FU NIH; Leducq Foundation FX We are grateful for the assistance of I. I. Rovira. This work was supported NIH Intramural Funds and the Leducq Foundation. NR 90 TC 116 Z9 117 U1 7 U2 39 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 1550-4131 EI 1932-7420 J9 CELL METAB JI Cell Metab. PD MAY 6 PY 2014 VL 19 IS 5 BP 757 EP 766 DI 10.1016/j.cmet.2014.01.011 PG 10 WC Cell Biology; Endocrinology & Metabolism SC Cell Biology; Endocrinology & Metabolism GA AG6XB UT WOS:000335561200006 PM 24561260 ER PT J AU Ilango, A Kesner, AJ Broker, CJ Wang, DV Ikemoto, S AF Ilango, Anton Kesner, Andrew J. Broker, Carl J. Wang, Dong V. Ikemoto, Satoshi TI Phasic excitation of ventral tegmental dopamine neurons potentiates the initiation of conditioned approach behavior: parametric and reinforcement-schedule analyses SO FRONTIERS IN BEHAVIORAL NEUROSCIENCE LA English DT Article DE phasic firing; optogenetics; conditioning; operant; reinforcement schedule; approach motivation; reward ID NUCLEUS-ACCUMBENS DOPAMINE; REWARD-SEEKING BEHAVIOR; OLFACTORY TUBERCLE; NEURAL ACTIVITY; RATS; STRIATUM; RELEASE; CHANNELRHODOPSIN-2; AMPHETAMINE; RECOMBINASE AB Midbrain dopamine neurons are implicated in motivation and learning. However, it is unclear how phasic excitation of dopamine neurons, which is implicated in learning, is involved in motivation. Here we used a self-stimulation procedure to examine how mice seek for optogenetically-induced phasic excitation of dopamine neurons, with an emphasis on the temporal dimension. TH-Cre transgenic mice received adeno-associated viral vectors encoding channelrhodopsin-2 into the ventral tegmental area, resulting in selective expression of the opsin in dopamine neurons. These mice were trained to press on a lever for photo-pulse trains that phasically excited dopamine neurons. They learned to self-stimulate in a fast, constant manner, and rapidly reduced pressing during extinction. We first determined effective parameters of photo-pulse trains in self-stimulation. Lever-press rates changed as a function of the manipulation of pulse number, duration, intensity, and frequency. We then examined effects of interval and ratio schedules of reinforcement on photo-pulse train reinforcement, which was contrasted with food reinforcement. Reinforcement with food inhibited lever pressing for a few seconds, after which pressing was robustly regulated in a goal-directed manner. In contrast, phasic excitation of dopamine neurons robustly potentiated the initiation of lever pressing; however, this effect did not last more than 1 s and quickly diminished. Indeed, response rates markedly decreased when lever pressing was reinforced with inter-reinforcement interval schedules of 3 or 10 s or ratio schedules requiring multiple responses per reinforcement. Thus, phasic excitation of dopamine neurons briefly potentiates the initiation of approach behavior with apparent lack of long-term motivational regulation. C1 [Ilango, Anton; Kesner, Andrew J.; Broker, Carl J.; Wang, Dong V.; Ikemoto, Satoshi] NIDA, Behav Neurosci Branch, NIH, Baltimore, MD 21224 USA. RP Ikemoto, S (reprint author), NIDA, 251 Bayview Blvd,Suite 200, Baltimore, MD 21224 USA. EM satoshi.ikemoto@nih.gov OI Ikemoto, Satoshi/0000-0002-0732-7386; Kesner, Andrew/0000-0002-3902-1955 FU National Institute on Drug Abuse, National Institutes of Health FX The present work was supported by the Intramural Research Program of National Institute on Drug Abuse, National Institutes of Health. We thank the NIDA-IRP Optogenetics and Transgenic Technology Core for providing viral vectors. NR 40 TC 8 Z9 8 U1 0 U2 7 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 MAY 6 PY 2014 VL 8 AR 155 DI 10.3389/fnbeh.2014.00155 PG 13 WC Behavioral Sciences; Neurosciences SC Behavioral Sciences; Neurosciences & Neurology GA AH2LG UT WOS:000335952300001 PM 24834037 ER PT J AU Beard, WA Wilson, SH AF Beard, William A. Wilson, Samuel H. TI Structure and Mechanism of DNA Polymerase beta SO BIOCHEMISTRY LA English DT Article ID BASE-EXCISION-REPAIR; TEMPLATING 8-OXOGUANINE LESION; STATE KINETIC-ANALYSIS; INDUCED-FIT MECHANISM; ACTIVE-SITE; CRYSTAL-STRUCTURE; NUCLEOTIDE INCORPORATION; CELLULAR-TRANSFORMATION; CATALYTIC MECHANISM; ENZYME SPECIFICITY AB DNA polymerase (pol) beta is a small eukaryotic DNA polymerase composed of two domains. Each domain contributes an enzymatic activity (DNA synthesis and deoxyribose phosphate lyase) during the repair of simple base lesions. These domains are termed the polymerase and lyase domains, respectively. Pol beta has been an excellent model enzyme for studying the nucleotidyl transferase reaction and substrate discrimination at a molecular level. In this review, recent crystallographic studies of pol beta in various liganded and conformational states during the insertion of right and wrong nucleotides as well as during the bypass of damaged DNA (apurinic sites and 8-oxoguanine) are described. Structures of these catalytic intermediates provide unexpected insights into mechanisms by which DNA polymerases enhance genome stability. These structures also provide an improved framework that permits computational studies to facilitate the interpretation of detailed kinetic analyses of this model enzyme. C1 [Beard, William A.; Wilson, Samuel H.] NIEHS, Struct Biol Lab, NIH, Res Triangle Pk, NC 27709 USA. RP Wilson, SH (reprint author), NIEHS, Struct Biol Lab, NIH, 111 TW Alexander Dr,POB 12233,MD F3-01, Res Triangle Pk, NC 27709 USA. EM wilson5@niehs.nih.gov FU Intramural Research Program of the National Institute of Environmental Health Sciences [Z01-ES050158, Z01-ES050159]; National Institutes of Health [1U19CA105010] FX This research was supported by Research Projects Z01-ES050158 and Z01-ES050159 (S.H.W.) of the Intramural Research Program of the National Institute of Environmental Health Sciences and was in association with National Institutes of Health Grant 1U19CA105010. NR 79 TC 27 Z9 28 U1 0 U2 28 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0006-2960 J9 BIOCHEMISTRY-US JI Biochemistry PD MAY 6 PY 2014 VL 53 IS 17 BP 2768 EP 2780 DI 10.1021/bi500139h PG 13 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA AG9EC UT WOS:000335720500003 PM 24717170 ER PT J AU Bebenek, K Pedersen, LC Kunkel, TA AF Bebenek, Katarzyna Pedersen, Lars C. Kunkel, Thomas A. TI Structure-Function Studies of DNA Polymerase lambda SO BIOCHEMISTRY LA English DT Article ID BASE-EXCISION-REPAIR; HUMAN POL-MU; HUMAN NUCLEAR EXTRACTS; GAP-FILLING SYNTHESIS; RIBONUCLEOTIDE INCORPORATION; REPLICATION FIDELITY; CRYSTAL-STRUCTURES; CATALYTIC CYCLE; THYMINE GLYCOL; BRCT DOMAIN AB DNA polymerase lambda (pol lambda) functions in DNA repair with its main roles considered to be filling short gaps during repair of double-strand breaks by nonhomologous end joining and during base excision repair. As indicated by structural and biochemical studies over the past 10 years, pol lambda shares many common properties with other family X siblings (pol beta, pol mu, and terminal deoxynucleotidyl transferase) but also has unique structural features that determine its specific functions. In this review, we consider how structural studies over the past decade furthered our understanding of the behavior and biological roles of pol lambda. C1 [Bebenek, Katarzyna; Pedersen, Lars C.; Kunkel, Thomas A.] NIEHS, Struct Biol Lab, NIH, Res Triangle Pk, NC 27709 USA. [Bebenek, Katarzyna; Kunkel, Thomas A.] NIEHS, Mol Genet Lab, NIH, Res Triangle Pk, NC 27709 USA. RP Bebenek, K (reprint author), NIEHS, Struct Biol Lab, NIH, POB 12233, Res Triangle Pk, NC 27709 USA. EM bebenek@niehs.nih.gov FU Division of Intramural Research of the National Institute of Environmental Health Sciences, National Institutes of Health [ES065070, ES102645] FX Work in the laboratories of T.A.K. and L.C.P. is supported by the Division of Intramural Research of the National Institute of Environmental Health Sciences, National Institutes of Health, via Grants ES065070 and ES102645, respectively. NR 86 TC 11 Z9 11 U1 2 U2 20 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0006-2960 J9 BIOCHEMISTRY-US JI Biochemistry PD MAY 6 PY 2014 VL 53 IS 17 BP 2781 EP 2792 DI 10.1021/bi4017236 PG 12 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA AG9EC UT WOS:000335720500004 PM 24716527 ER PT J AU Yang, W AF Yang, Wei TI An Overview of Y-Family DNA Polymerases and a Case Study of Human DNA Polymerase eta SO BIOCHEMISTRY LA English DT Article ID PIGMENTOSUM-VARIANT PATIENTS; SYN THYMINE DIMER; ERROR-FREE BYPASS; ACCURATE TRANSLESION SYNTHESIS; REV1 PROTEIN INTERACTS; SINGLE-BASE DELETIONS; STRUCTURAL BASIS; SULFOLOBUS-SOLFATARICUS; XERODERMA-PIGMENTOSUM; CRYSTAL-STRUCTURE AB Y-Family DNA polymerases specialize in translesion synthesis, bypassing damaged bases that would otherwise block the normal progression of replication forks. Y-Family polymerases have unique structural features that allow them to bind damaged DNA and use a modified template base to direct nucleotide incorporation. Each Y-Family polymerase is unique and has different preferences for lesions to bypass and for dNTPs to incorporate. Y-Family polyrnerases are also characterized by a low catalytic efficiency, a low processivity, and a low fidelity on normal DNA. Recruitment of these specialized polymerases to replication forks is therefore regulated. The catalytic center of the Y-Family polymerases is highly conserved and homologous to that of high-fidelity and high-processivity DNA replicases. In this review, structural differences between Y-Family and A- and B-Family polymerases are compared and correlated with their functional differences. A time-resolved X-ray crystallographic study of the DNA synthesis reaction catalyzed by the Y-Family DNA polymerase human polyrnerase eta revealed transient elements that led to the nucleotidyl-transfer reaction. C1 NIDDK, Mol Biol Lab, NIH, Bethesda, MD 20892 USA. RP Yang, W (reprint author), NIDDK, Mol Biol Lab, NIH, Bethesda, MD 20892 USA. EM wei.yang@nih.gov RI Yang, Wei/D-4926-2011 OI Yang, Wei/0000-0002-3591-2195 FU National Institutes of Health Intramural Program [DK036146-07] FX This work is funded by the National Institutes of Health Intramural Program (DK036146-07). NR 163 TC 41 Z9 41 U1 2 U2 28 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0006-2960 J9 BIOCHEMISTRY-US JI Biochemistry PD MAY 6 PY 2014 VL 53 IS 17 BP 2793 EP 2803 DI 10.1021/bi500019s PG 11 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA AG9EC UT WOS:000335720500005 PM 24716551 ER PT J AU Sodt, AJ Pastor, RW AF Sodt, Alexander J. Pastor, Richard W. TI Molecular Modeling of Lipid Membrane Curvature Induction by a Peptide: More than Simply Shape SO BIOPHYSICAL JOURNAL LA English DT Article ID BAR DOMAINS; AMPHIPATHIC HELICES; PHOSPHOLIPID-MEMBRANES; DYNAMICS SIMULATIONS; BILAYER INTERACTIONS; ELASTIC PROPERTIES; CRYSTAL-STRUCTURE; HEXAGONAL PHASES; CURVED MEMBRANES; SURFACE-TENSION AB Molecular dynamics simulations of an amphipathic helix embedded in a lipid bilayer indicate that it will induce substantial positive curvature (e.g., a tube of diameter 20 nm at 16% surface coverage). The induction is twice that of a continuum model prediction that only considers the shape of the inclusion. The discrepancy is explained in terms of the additional presence of specific interactions described only by the molecular model. The conclusion that molecular shape alone is insufficient to quantitatively model curvature is supported by contrasting molecular and continuum models of lipids with large and small headgroups (choline and ethanolamine, respectively), and of the removal of a lipid tail (modeling a lyso-lipid). For the molecular model, curvature propensity is analyzed by computing the derivative of the free energy with respect to bending. The continuum model predicts that the inclusion will soften the bilayer near the headgroup region, an effect that may weaken curvature induction. The all-atom predictions are consistent with experimental observations of the degree of tubulation by amphipathic helices and variation of the free energy of binding to liposomes. C1 [Sodt, Alexander J.; Pastor, Richard W.] NHLBI, NIH, Rockville, MD USA. RP Sodt, AJ (reprint author), NHLBI, NIH, Rockville, MD USA. EM alexsodt@gmail.com FU Intramural Research Program of the National Institutes of Health, National Heart, Lung and Blood Institute (NIMBI) FX This research was supported by the Intramural Research Program of the National Institutes of Health, National Heart, Lung and Blood Institute (NIMBI), and utilized the high-performance computational capabilities at the National Institutes of Health, Bethesda, MD (NIMBI LoBoS cluster). NR 62 TC 16 Z9 16 U1 2 U2 58 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 MAY 6 PY 2014 VL 106 IS 9 BP 1958 EP 1969 DI 10.1016/j.bpj.2014.02.037 PG 12 WC Biophysics SC Biophysics GA AG7PM UT WOS:000335610100018 PM 24806928 ER PT J AU Schmitt, JE Neale, MC Fassassi, B Perez, J Lenroot, RK Wells, EM Giedd, JN AF Schmitt, J. Eric Neale, Michael C. Fassassi, Bilqis Perez, Javier Lenroot, Rhoshel K. Wells, Elizabeth M. Giedd, Jay N. TI The dynamic role of genetics on cortical patterning during childhood and adolescence SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE neurodevelopment; twin research ID HUMAN CEREBRAL-CORTEX; AUTOMATED 3-D EXTRACTION; FALSE DISCOVERY RATE; BRAIN STRUCTURE; GROWTH-CURVES; MRI DATA; THICKNESS; EVOLUTION; SURFACES; CHILDREN AB Longitudinal imaging and quantitative genetic studies have both provided important insights into the nature of human brain development. In the present study we combine these modalities to obtain dynamic anatomical maps of the genetic contributions to cortical thickness through childhood and adolescence. A total of 1,748 anatomic MRI scans from 792 healthy twins and siblings were studied with up to eight time points per subject. Using genetically informative latent growth curve modeling of 81,924 measures of cortical thickness, changes in the genetic contributions to cortical development could be visualized across the age range at high resolution. There was highly statistically significant (P < 0.0001) genetic variance throughout the majority of the cerebral cortex, with the regions of highest heritability including the most evolutionarily novel regions of the brain. Dynamic modeling of changes in heritability over time demonstrated that the heritability of cortical thickness increases gradually throughout late childhood and adolescence, with sequential emergence of three large regions of high heritability in the temporal poles, the inferior parietal lobes, and the superior and dorsolateral frontal cortices. C1 [Schmitt, J. Eric] Hosp Univ Penn, Dept Radiol, Philadelphia, PA 19104 USA. [Neale, Michael C.; Perez, Javier] Virginia Commonwealth Univ, Virginia Inst Psychiat & Behav Genet, Dept Psychiat, Richmond, VA 23298 USA. [Fassassi, Bilqis; Wells, Elizabeth M.; Giedd, Jay N.] NIMH, Pediat Imaging Unit, Bethesda, MD 20892 USA. [Lenroot, Rhoshel K.] Univ New S Wales, Sch Psychiat & Neurosci Res Australia, Sydney, NSW 2052, Australia. RP Schmitt, JE (reprint author), Hosp Univ Penn, Dept Radiol, 3400 Spruce St, Philadelphia, PA 19104 USA. EM eric.schmitt@stanfordalumni.org RI Giedd, Jay/J-9644-2015 OI Giedd, Jay/0000-0003-2002-8978 FU National Institutes of Health [MH-20030, EB-004311] FX This work was supported by National Institutes of Health Grants MH-20030 and EB-004311. NR 44 TC 25 Z9 25 U1 2 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 MAY 6 PY 2014 VL 111 IS 18 BP 6774 EP 6779 DI 10.1073/pnas.1311630111 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA AG5RX UT WOS:000335477300063 PM 24753564 ER PT J AU Takagi, Y Farrow, RE Billington, N Nagy, A Batters, C Yang, Y Sellers, JR Molloy, JE AF Takagi, Yasuharu Farrow, Rachel E. Billington, Neil Nagy, Attila Batters, Christopher Yang, Yi Sellers, James R. Molloy, Justin E. TI Myosin-10 produces its power-stroke in two phases and moves processively along a single actin filament under low load SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE actomyosin; stable single alpha-helix; optical trapping; myosin X; myosin-5a ID MUSCLE HEAVY-MEROMYOSIN; SMOOTH-MUSCLE; OPTICAL TWEEZERS; MOLECULAR MOTOR; COILED-COIL; STEP-SIZE; LEUCINE-ZIPPER; WORKING STROKE; BUNDLED ACTIN; NECK LENGTH AB Myosin-10 is an actin-based molecular motor that participates in essential intracellular processes such as filopodia formation/extension, phagocytosis, cell migration, and mitotic spindle maintenance. To study this motor protein's mechano-chemical properties, we used a recombinant, truncated form of myosin-10 consisting of the first 936 amino acids, followed by a GCN4 leucine zipper motif, to force dimerization. Negative-stain electron microscopy reveals that the majority of molecules are dimeric with a head-to-head contour distance of similar to 50 nm. In vitro motility assays show that myosin10 moves actin filaments smoothly with a velocity of similar to 310 nm/s. Steady-state and transient kinetic analysis of the ATPase cycle shows that the ADP release rate (similar to 13 s(-1)) is similar to the maximum ATPase activity (similar to 12-14 s(-1)) and therefore contributes to rate limitation of the enzymatic cycle. Single molecule optical tweezers experiments show that under intermediate load (similar to 0.5 pN), myosin-10 interacts intermittently with actin and produces a power stroke of similar to 17 nm, composed of an initial 15-nm and subsequent 2-nm movement. At low optical trap loads, we observed staircase-like processive movements of myosin-10 interacting with the actin filament, consisting of up to six similar to 35-nm steps per binding interaction. We discuss the implications of this load-dependent processivity of myosin-10 as a filopodial transport motor. C1 [Takagi, Yasuharu; Billington, Neil; Nagy, Attila; Yang, Yi; Sellers, James R.] NHLBI, Lab Mol Physiol, NIH, Bethesda, MD 20892 USA. [Farrow, Rachel E.; Batters, Christopher; Molloy, Justin E.] Natl Inst Med Res, MRC, Div Phys Biochem, London NW7 1AA, England. RP Sellers, JR (reprint author), NHLBI, Lab Mol Physiol, NIH, Bldg 10, Bethesda, MD 20892 USA. EM sellersj@nhlbi.nih.gov; jmolloy@nimr.mrc.ac.uk FU National Natural Science Foundation of China [31270819]; NHLBI [HL004243 12]; Medical Research Council [U1175.70592] FX We thank Keir C. Neuman and Earl Homsher for critical reading of the manuscript, as well as for helpful discussions; David P. Corey (Harvard University) for the cDNA clone of the Bos taurus myosin-10 heavy chain; the Electron Microscopy Core Facility at the National Heart, Lung and Blood Institute (NHLBI), National Institutes of Health (NIH), for the use of the equipment; the members of the Laboratory of Molecular Physiology, NHLBI, NIH; and the Division of Physical Biochemistry, Medical Research Council National Institute for Medical Research, for technical assistance. Y.Y. was supported by National Natural Science Foundation of China Grant 31270819. This work was funded by the intramural funds from NHLBI Grant HL004243 12 (to J.R.S.) and Medical Research Council Grant U1175.70592 (to J.E.M.). NR 75 TC 12 Z9 12 U1 1 U2 27 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 MAY 6 PY 2014 VL 111 IS 18 BP E1833 EP E1842 DI 10.1073/pnas.1320122111 PG 10 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA AG5RX UT WOS:000335477300007 PM 24753602 ER PT J AU Burotto, M Wilkerson, J Stein, W Motzer, R Bates, S Fojo, T AF Burotto, Mauricio Wilkerson, Julia Stein, Wilfred Motzer, Robert Bates, Susan Fojo, Tito TI Continuing a Cancer Treatment Despite Tumor Growth May Be Valuable: Sunitinib in Renal Cell Carcinoma as Example SO PLOS ONE LA English DT Article ID PHASE-III TRIAL; TYROSINE KINASE INHIBITORS; INTERFERON-ALPHA; ACQUIRED-RESISTANCE; SOLID TUMORS; DOUBLE-BLIND; LUNG-CANCER; SURVIVAL; PROGRESSION; SORAFENIB AB Background: The US FDA and the EMA have approved seven agents for the treatment of renal cell carcinoma, primarily based on differences in progression-free survival (PFS). Because PFS is an arbitrary endpoint we hypothesized that an analysis would demonstrate the growth rate of tumors remained constant at the time of RECIST-defined disease progression. Methods: We previously estimated the growth (g) and regression (d) rates and the stability of g using data from the Phase III trial comparing sunitinib and interferon. Results: Sufficient data were available and rate constants statistically valid in 321 of 374 patients randomized to sunitinib. Median d was 0.0052 days(-1); in 53 patients no tumor growth was recorded. Median g was 0.00082 days(-1) and was stable for a median of 275 days on therapy, remaining stable beyond 300, 600 and 900 days in 122, 65 and 27 patients, respectively. A possible increase in g while receiving sunitinib could be discerned in only 18 of 321 patients. Given a median g of 0.00082 days 21 the estimated median time to a second progression were sunitinib continued past RECIST-defined progression was 7.3 months. At 100, 200, and 300 days after starting therapy, an estimated 47%, 27%, and 13% of tumor remains sunitinib sensitive and could explain a RECIST-defined response to a new TKI. Conclusion: Prolonged stability of g with sunitinib suggests continued sunitinib beyond RECIST-defined progression may provide a beneficial outcome. Randomized trials in patients whose disease has "progressed" on sunitinib are needed to test this hypothesis. C1 [Burotto, Mauricio; Wilkerson, Julia; Stein, Wilfred; Bates, Susan; Fojo, Tito] NCI, Med Oncol Branch, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. [Stein, Wilfred] Hebrew Univ Jerusalem, Jerusalem, Israel. [Motzer, Robert] Mem Sloan Kettering Canc Ctr, New York, NY USA. RP Burotto, M (reprint author), NCI, Med Oncol Branch, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. EM mauricio.burottopichun@nih.gov OI Wilkerson, Julia/0000-0002-6965-0867 FU Intramural Research Program of the National Institutes of Health, National Cancer Institute, Center for Cancer Research FX This research was supported by the Intramural Research Program of the National Institutes of Health, National Cancer Institute, Center for Cancer Research. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 26 TC 6 Z9 6 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 MAY 5 PY 2014 VL 9 IS 5 AR e96316 DI 10.1371/journal.pone.0096316 PG 8 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA AI1ZV UT WOS:000336656000063 PM 24796484 ER PT J AU Keleshian, VL Kellom, M Kim, HW Taha, AY Cheon, Y Igarashi, M Rapoport, SI Rao, JS AF Keleshian, Vasken L. Kellom, Matthew Kim, Hyung-Wook Taha, Ameer Y. Cheon, Yewon Igarashi, Miki Rapoport, Stanley I. Rao, Jagadeesh S. TI Neuropathological Responses to Chronic NMDA in Rats Are Worsened by Dietary n-3 PUFA Deprivation but Are Not Ameliorated by Fish Oil Supplementation SO PLOS ONE LA English DT Article ID POLYUNSATURATED FATTY-ACIDS; ALPHA-LINOLENIC ACID; FRONTAL-CORTEX; DOCOSAHEXAENOIC ACID; ARACHIDONIC-ACID; DOUBLE-BLIND; UNANESTHETIZED RATS; BRAIN; LIVER; METABOLISM AB Background: Dietary long-chain n-3 polyunsaturated fatty acid (PUFA) supplementation may be beneficial for chronic brain illnesses, but the issue is not agreed on. We examined effects of dietary n-3 PUFA deprivation or supplementation, compared with an n-3 PUFA adequate diet (containing alpha-linolenic acid [18: 3 n-3] but not docosahexaenoic acid [DHA, 22: 6n-3]), on brain markers of lipid metabolism and excitotoxicity, in rats treated chronically with NMDA or saline. Methods: Male rats after weaning were maintained on one of three diets for 15 weeks. After 12 weeks, each diet group was injected i.p. daily with saline (1 ml/kg) or a subconvulsive dose of NMDA (25 mg/kg) for 3 additional weeks. Then, brain fatty acid concentrations and various markers of excitotoxicity and fatty acid metabolism were measured. Results: Compared to the diet-adequate group, brain DHA concentration was reduced, while n-6 docosapentaenoic acid (DPA, 22: 5n-6) concentration was increased in the n-3 deficient group; arachidonic acid (AA, 20: 4n-6) concentration was unchanged. These concentrations were unaffected by fish oil supplementation. Chronic NMDA increased brain cPLA(2) activity in each of the three groups, but n-3 PUFA deprivation or fish oil did not change cPLA(2) activity or protein compared with the adequate group. sPLA(2) expression was unchanged in the three conditions, whereas iPLA(2) expression was reduced by deprivation but not changed by supplementation. BDNF protein was reduced by NMDA in N-3 PUFA deficient rats, but protein levels of IL-1 beta, NGF, and GFAP did not differ between groups. Conclusions: N-3 PUFA deprivation significantly worsened several pathological NMDA-induced changes produced in diet adequate rats, whereas n-3 PUFA supplementation did not affect NMDA induced changes. Supplementation may not be critical for this measured neuropathology once the diet has an adequate n-3 PUFA content. C1 [Keleshian, Vasken L.] Virginia Commonwealth Univ, Sch Med, Richmond, VA USA. [Kellom, Matthew] Arizona State Univ, Sch Earth & Space Explorat, Phoenix, AZ USA. [Kim, Hyung-Wook] Sejong Univ, Coll Life Sci, Seoul, South Korea. [Taha, Ameer Y.; Cheon, Yewon; Rapoport, Stanley I.; Rao, Jagadeesh S.] NIA, Brain Physiol & Metab Sect, Neurosci Lab, NIH, Bethesda, MD 20892 USA. RP Rao, JS (reprint author), NIA, Brain Physiol & Metab Sect, Neurosci Lab, NIH, Bethesda, MD 20892 USA. EM jrao@mail.nih.gov FU Office of Dietary Supplementation awarded [OD-09-085]; intramural program of National Institute on Aging, NIH FX This research was supported by a grant from the Office of Dietary Supplementation awarded to J.S. Rao (Grant #OD-09-085) and the intramural program of National Institute on Aging, 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 6 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 MAY 5 PY 2014 VL 9 IS 5 AR e95318 DI 10.1371/journal.pone.0095318 PG 9 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA AI1ZV UT WOS:000336656000017 PM 24798187 ER PT J AU Jjingo, D Conley, AB Wang, JR Marino-Ramirez, L Lunyak, VV Jordan, IK AF Jjingo, Daudi Conley, Andrew B. Wang, Jianrong Marino-Ramirez, Leonardo Lunyak, Victoria V. Jordan, I. King TI Mammalian-wide interspersed repeat (MIR)-derived enhancers and the regulation of human gene expression SO MOBILE DNA LA English DT Article ID PROTEIN-DNA INTERACTIONS; TRANSPOSABLE ELEMENTS; TRANSCRIPTION FACTOR; HUMAN GENOME; BINDING-SITES; STEM-CELLS; K562 CELLS; C-JUN; DATABASE; EVOLUTION AB Background: Mammalian-wide interspersed repeats (MIRs) are the most ancient family of transposable elements (TEs) in the human genome. The deep conservation of MIRs initially suggested the possibility that they had been exapted to play functional roles for their host genomes. MIRs also happen to be the only TEs whose presence in-and-around human genes is positively correlated to tissue-specific gene expression. Similar associations of enhancer prevalence within genes and tissue-specific expression, along with MIRs' previous implication as providing regulatory sequences, suggested a possible link between MIRs and enhancers. Results: To test the possibility that MIRs contribute functional enhancers to the human genome, we evaluated the relationship between MIRs and human tissue-specific enhancers in terms of genomic location, chromatin environment, regulatory function, and mechanistic attributes. This analysis revealed MIRs to be highly concentrated in enhancers of the K562 and HeLa human cell-types. Significantly more enhancers were found to be linked to MIRs than would be expected by chance, and putative MIR-derived enhancers are characterized by a chromatin environment highly similar to that of canonical enhancers. MIR-derived enhancers show strong associations with gene expression levels, tissue-specific gene expression and tissue-specific cellular functions, including a number of biological processes related to erythropoiesis. MIR-derived enhancers were found to be a rich source of transcription factor binding sites, underscoring one possible mechanistic route for the element sequences co-option as enhancers. There is also tentative evidence to suggest that MIR-enhancer function is related to the transcriptional activity of non-coding RNAs. Conclusions: Taken together, these data reveal enhancers to be an important cis-regulatory platform from which MIRs can exercise a regulatory function in the human genome and help to resolve a long-standing conundrum as to the reason for MIRs' deep evolutionary conservation. C1 [Jjingo, Daudi; Conley, Andrew B.; Wang, Jianrong] Georgia Inst Technol, Sch Biol, Atlanta, GA 30332 USA. [Marino-Ramirez, Leonardo] Natl Lib Med, Natl Ctr Biotechnol Informat, NIH, Bethesda, MD 20894 USA. [Marino-Ramirez, Leonardo; Lunyak, Victoria V.; Jordan, I. King] PanAmer Bioinformat Inst, Santa Marta, Magdalena, Colombia. [Lunyak, Victoria V.] Buck Inst Res Aging, Novato, CA USA. RP Jordan, IK (reprint author), Georgia Inst Technol, Sch Biol, Atlanta, GA 30332 USA. EM king.jordan@biology.gatech.edu OI Marino-Ramirez, Leonardo/0000-0002-5716-8512 FU Fulbright foundation; School of Biology, Georgia Institute of Technology; Alfred P Sloan Research Fellowship in Computational and Evolutionary Molecular Biology [BR-4839]; Intramural Research Program of the NIH, NLM, NCBI; NIH [R21 AG043921] FX This work was supported in part by the Fulbright foundation through a PhD scholarship to DJ, the School of Biology, Georgia Institute of Technology (to IKJ, DJ, ABC, and JW), an Alfred P Sloan Research Fellowship in Computational and Evolutionary Molecular Biology (BR-4839) to IKJ, and NIH R21 AG043921 to WL. This research was supported in part by the Intramural Research Program of the NIH, NLM, NCBI. No funding bodies played any role in the design, collection, analysis, and interpretation of the data or the writing and submission of the manuscript. The authors would like to acknowledge members of the Jordan laboratory for helpful discussions. The authors are also grateful to the ENCODE consortium for making their data freely accessible and acknowledge the use of data generated by the ENCODE institutions and groups below: Broad Institute and Massachusetts General Hospital-Harvard Medical School/Bernstein Laboratory (histone modifications data). Stanford University/Michael Snyder laboratory, Yale University/Mark Gerstein and Sherman Weissman laboratories, University of Southern California/ Peggy Farnham Laboratory and Harvard University/Kevin Struhl Laboratory (transcription-factor binding data) and University of Washington/Sandstrom laboratory (expression data). NR 73 TC 9 Z9 9 U1 2 U2 6 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1759-8753 J9 MOBILE DNA-UK JI Mob. DNA PD MAY 5 PY 2014 VL 5 AR 14 DI 10.1186/1759-8753-5-14 PG 12 WC Genetics & Heredity SC Genetics & Heredity GA AH4BL UT WOS:000336070400001 PM 25018785 ER PT J AU Guerard, F Lee, YS Brechbiel, MW AF Guerard, Francois Lee, Yong-Sok Brechbiel, Martin W. TI Rational Design, Synthesis, and Evaluation of Tetrahydroxamic Acid Chelators for Stable Complexation of Zirconium( IV) SO CHEMISTRY-A EUROPEAN JOURNAL LA English DT Article DE chelates; imaging agents; ligand design; quantum chemistry; zirconium ID P-ISOTHIOCYANATOBENZYL-DESFERRIOXAMINE; POSITRON-EMITTING RADIONUCLIDES; MONOCLONAL-ANTIBODIES; BIFUNCTIONAL CHELATE; EMISSION-TOMOGRAPHY; HYDROXAMIC ACIDS; PET; CHEMISTRY; ZR-89; CHALLENGES AB Metals of interest for biomedical applications often need to be complexed and associated in a stable manner with a targeting agent before use. Whereas the fundamentals of most transition-metal complexation processes have been thoroughly studied, the complexation of Zr-IV has been somewhat neglected. This metal has received growing attention in recent years, especially in nuclear medicine, with the use of Zr-89, which a (+)-emitter with near ideal characteristics for cancer imaging. However, the best chelating agent known for this radionuclide is the trishydroxamate desferrioxamineB (DFB), the Zr-IV complex of which exhibits suboptimal stability, resulting in the progressive release of Zr-89 in vivo. Based on a recent report demonstrating the higher thermodynamic stability of the tetrahydroxamate complexes of Zr-IV compared with the trishydroxamate complexes analogues to DFB, we designed a series of tetrahydroxamic acids of varying geometries for improved complexation of this metal. Three macrocycles differing in their cavity size (28 to 36-membered rings) were synthesized by using a ring-closing metathesis strategy, as well as their acyclic analogues. A solution study with Zr-89 showed the complexation to be more effective with increasing cavity size. Evaluation of the kinetic inertness of these new complexes in ethylenediaminetetraacetic acid (EDTA) solution showed significantly improved stabilities of the larger chelates compared with Zr-89-DFB, whereas the smaller complexes suffered from insufficient stabilities. These results were rationalized by a quantum chemical study. The lower stability of the smaller chelates was attributed to ring strain, whereas the better stability of the larger cyclic complexes was explained by the macrocyclic effect and by the structural rigidity. Overall, these new chelating agents open new perspectives for the safe and efficient use of Zr-89 in nuclear imaging, with the best chelators providing dramatically improved stabilities compared with the reference DFB. C1 [Guerard, Francois; Brechbiel, Martin W.] NCI, Radioimmune & Inorgan Chem Sect, Radiat Oncol Branch, NIH, Bethesda, MD 20892 USA. [Lee, Yong-Sok] NIH, Ctr Mol Modeling, Div Computat Biosci, Bethesda, MD 20892 USA. RP Guerard, F (reprint author), NCI, Radioimmune & Inorgan Chem Sect, Radiat Oncol Branch, NIH, Bethesda, MD 20892 USA. EM francois.guerard@univ-nantes.fr OI Guerard, Francois/0000-0001-9795-2785 FU Intramural Research Program of the NIH, National Cancer Institute, Center for Cancer Research; Center for Information Technology FX This work was supported by the Intramural Research Program of the NIH, National Cancer Institute, Center for Cancer Research and the Center for Information Technology. The quantum chemical study utilized PC/LINUX clusters at the Center for Molecular Modeling of the NIH (http://cit.nih.gov). The authors are grateful to Dr. L. P. Szajek at the PET department for providing 89Zr. NR 30 TC 21 Z9 21 U1 4 U2 35 PU WILEY-V C H VERLAG GMBH PI WEINHEIM PA BOSCHSTRASSE 12, D-69469 WEINHEIM, GERMANY SN 0947-6539 EI 1521-3765 J9 CHEM-EUR J JI Chem.-Eur. J. PD MAY 5 PY 2014 VL 20 IS 19 BP 5584 EP 5591 DI 10.1002/chem.201304115 PG 8 WC Chemistry, Multidisciplinary SC Chemistry GA AG1SS UT WOS:000335197000011 PM 24740517 ER PT J AU Pindolia, DK Garcia, AJ Huang, ZJ Fik, T Smith, DL Tatem, AJ AF Pindolia, Deepa K. Garcia, Andres J. Huang, Zhuojie Fik, Timothy Smith, David L. Tatem, Andrew J. TI Quantifying cross-border movements and migrations for guiding the strategic planning of malaria control and elimination SO MALARIA JOURNAL LA English DT Article ID PLASMODIUM-FALCIPARUM; TRANSMISSION; RISK; AFRICA; SWAZILAND; ZANZIBAR; TRAVEL; ENDEMICITY; PATTERNS; SYSTEM AB Background: Identifying human and malaria parasite movements is important for control planning across all transmission intensities. Imported infections can reintroduce infections into areas previously free of infection, maintain 'hotspots' of transmission and import drug resistant strains, challenging national control programmes at a variety of temporal and spatial scales. Recent analyses based on mobile phone usage data have provided valuable insights into population and likely parasite movements within countries, but these data are restricted to sub-national analyses, leaving important cross-border movements neglected. Methods: National census data were used to analyse and model cross-border migration and movement, using East Africa as an example. 'Hotspots' of origin-specific immigrants from neighbouring countries were identified for Kenya, Tanzania and Uganda. Populations of origin-specific migrants were compared to distance from origin country borders and population size at destination, and regression models were developed to quantify and compare differences in migration patterns. Migration data were then combined with existing spatially-referenced malaria data to compare the relative propensity for cross-border malaria movement in the region. Results: The spatial patterns and processes for immigration were different between each origin and destination country pair. Hotspots of immigration, for example, were concentrated close to origin country borders for most immigrants to Tanzania, but for Kenya, a similar pattern was only seen for Tanzanian and Ugandan immigrants. Regression model fits also differed between specific migrant groups, with some migration patterns more dependent on population size at destination and distance travelled than others. With these differences between immigration patterns and processes, and heterogeneous transmission risk in East Africa and the surrounding region, propensities to import malaria infections also likely show substantial variations. Conclusion: This was a first attempt to quantify and model cross-border movements relevant to malaria transmission and control. With national census available worldwide, this approach can be translated to construct a cross-border human and malaria movement evidence base for other malaria endemic countries. The outcomes of this study will feed into wider efforts to quantify and model human and malaria movements in endemic regions to facilitate improved intervention planning, resource allocation and collaborative policy decisions. C1 [Pindolia, Deepa K.; Garcia, Andres J.] Univ Florida, Emerging Pathogens Inst, Gainesville, FL 32611 USA. [Pindolia, Deepa K.; Garcia, Andres J.; Fik, Timothy] Univ Florida, Dept Geog, Gainesville, FL 32611 USA. [Pindolia, Deepa K.] Clinton Hlth Access Initiat, Boston, MA USA. [Huang, Zhuojie] Penn State Univ, Ctr Infect Dis Dynam, University Pk, PA 16802 USA. [Huang, Zhuojie] Penn State Univ, Dept Biol, University Pk, PA 16802 USA. [Smith, David L.] Johns Hopkins Bloomberg Sch Publ Hlth, Dept Epidemiol, Baltimore, MD USA. [Smith, David L.; Tatem, Andrew J.] NIH, Fogarty Int Ctr, Bethesda, MD 20892 USA. [Tatem, Andrew J.] Univ Southampton, Dept Geog & Environm, Southampton, Hants, England. RP Pindolia, DK (reprint author), Univ Florida, Emerging Pathogens Inst, Gainesville, FL 32611 USA. EM dpindolia@gmail.com RI Emchi, Karma/Q-1952-2016; Smith, David/L-8850-2013 OI Smith, David/0000-0003-4367-3849 FU Emerging Pathogens Institute; University of Florida; RAPIDD program of the Science and Technology Directorate; Department of Homeland Security; Fogarty International Center; National Institutes of Health; NIH/NIAID [U19AI089674]; Bloomberg Family Foundation FX The authors acknowledge the Spatial Epidemiology Unit at the Department of Public Health Research, KEMRI-Wellcome Trust in Kenya, for data acquisition support and thank Victor Alegana, Abdisalan Noor and Robert Snow for their contributions during the data compilation and conceptualization stages of this manuscript. AJT & DLS acknowledge funding support from the Emerging Pathogens Institute, University of Florida, the RAPIDD program of the Science and Technology Directorate, Department of Homeland Security, and the Fogarty International Center, National Institutes of Health, and are also supported by grants from NIH/NIAID (U19AI089674) and the Bill and Melinda Gates Foundation (#49446 and #1032350). DLS acknowledges funding support from Bloomberg Family Foundation. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. This paper forms part of the output of the WorldPop population mapping project (www.worldpop.org.uk), Flowminder (www.flowminder.org) and the human mobility mapping project (www.thummp.org). NR 48 TC 10 Z9 10 U1 2 U2 7 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1475-2875 J9 MALARIA J JI Malar. J. PD MAY 3 PY 2014 VL 13 AR 169 DI 10.1186/1475-2875-13-169 PG 11 WC Infectious Diseases; Parasitology; Tropical Medicine SC Infectious Diseases; Parasitology; Tropical Medicine GA AL2IJ UT WOS:000338948900001 PM 24886389 ER PT J AU Golubic, R Martin, KR Ekelund, U Hardy, R Kuh, D Wareham, N Cooper, R Brage, S AF Golubic, Rajna Martin, Kathryn R. Ekelund, Ulf Hardy, Rebecca Kuh, Diana Wareham, Nicholas Cooper, Rachel Brage, Soren CA NSHD Sci Team Data Collection Team TI Levels of physical activity among a nationally representative sample of people in early old age: results of objective and self-reported assessments SO INTERNATIONAL JOURNAL OF BEHAVIORAL NUTRITION AND PHYSICAL ACTIVITY LA English DT Article DE Physical activity; Sedentary behaviour; Physical activity questionnaire; Combined sensing; Birth cohort; Old age ID ACTIVITY ENERGY-EXPENDITURE; CORONARY-HEART-DISEASE; BRITISH BIRTH COHORT; ALL-CAUSE MORTALITY; ACTIVITY QUESTIONNAIRE; POSTMENOPAUSAL WOMEN; ACTIVITY PATTERNS; PAID EMPLOYMENT; ADULTS; HEALTH AB Background: Detailed assessment of physical activity (PA) in older adults is required to comprehensively describe habitual PA-levels in this growing population segment. Current evidence of population PA-levels is predominantly based on self-report. Methods: We examined PA and sedentary behaviour in a nationally representative sample of British people aged 60-64, using individually-calibrated combined heart-rate and movement sensing and a validated questionnaire (EPAQ2), and the socio-demographic and behavioural factors that may explain between-individual variation in PA. Results: Between 2006-2010, 2224 participants completed EPAQ2 capturing the past year's activity in four domains (leisure, work, transportation and domestic life) and 1787 participants provided 2-5 days of combined-sensing data. According to objective estimates, median(IQR) physical activity energy expenditure (PAEE) was 33.5 (25.3-42.2) and 35.5 (26.6-47.3) kJ/kg/day for women and men, respectively. Median (IQR) time spent in moderate-to-vigorous PA (MVPA; >3MET), light-intensity PA (1.5-3 MET) and sedentary (<1.5 MET) was 26.0 (12.3-48.1) min/day, 5.4 (4.2-6.7) h/day and 18.0 (16.6-19.4) h/day, respectively, in women; and 41.0 (18.8-73.0) min/day, 5.2 (4.0-6.5) h/day and 17.9 (16.3-19.4) h/day in men. PAEE and time spent in MVPA were lower and sedentary time was greater in obese individuals, those with poor health, and those with lower educational attainment (women only). Questionnaire-derived PAEE and MVPA tended to have similar patterns of variation across socio-demographic strata. In the whole sample, domestic PA had the greatest relative contribution to total questionnaire-derived PAEE (58%), whereas occupational PA was the main driver among employed participants (54%). Only 2.2% of participants achieved an average of >30 min MVPA per day combined with >60 min strength-training per week. Conclusions: The use of both self-report and objective monitoring to assess PA in early old age provides important information on the domains of PA, PAEE and time spent at different intensity levels. Our findings suggest PA levels are generally low and observed patterns of variation indicate specific subgroups who might benefit from targeted interventions to increase PA. C1 [Golubic, Rajna; Ekelund, Ulf; Wareham, Nicholas; Brage, Soren] Univ Cambridge, Inst Metab Sci, MRC, Epidemiol Unit,Addenbrookes Hosp, Cambridge CB2 0QQ, England. [Martin, Kathryn R.; Hardy, Rebecca; Kuh, Diana; Cooper, Rachel] UCL, Unit Lifelong Hlth & Ageing, MRC, London WC1B 5JU, England. [Martin, Kathryn R.] NIA, Lab Epidemiol & Populat Sci, Bethesda, MD 20892 USA. [Martin, Kathryn R.] Univ Aberdeen, Inst Appl Hlth Sci, Sch Med & Dent, Aberdeen AB25 2ZD, Scotland. [Ekelund, Ulf] Norwegian Sch Sport Sci, Dept Sport Med, N-0806 Oslo, Norway. RP Golubic, R (reprint author), Univ Cambridge, Inst Metab Sci, MRC, Epidemiol Unit,Addenbrookes Hosp, Box 285,Hills Rd, Cambridge CB2 0QQ, England. EM rajna.golubic@mrc-epid.cam.ac.uk OI Cooper, Rachel/0000-0003-3370-5720 FU MRC programme [MC_UU_12015/3, MC_UU_12019/1]; Intramural Research Program of the National Institute on Aging, NIH; Gates Cambridge Trust; St. John's College Cambridge; School of Clinical Medicine, University of Cambridge FX This work was supported by the MRC programme codes MC_UU_12015/3 and MC_UU_12019/1, and in part by the Intramural Research Program of the National Institute on Aging, NIH. Rajna Golubic is financially supported by a scholarship from the Gates Cambridge Trust, Benefactors' Scholarship from St. John's College Cambridge and Raymond and Beverly Sackler Studentship from the School of Clinical Medicine, University of Cambridge. NR 68 TC 19 Z9 19 U1 5 U2 17 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1479-5868 J9 INT J BEHAV NUTR PHY JI Int. J. Behav. Nutr. Phys. Act. PD MAY 3 PY 2014 VL 11 AR 58 DI 10.1186/1479-5868-11-58 PG 17 WC Nutrition & Dietetics; Physiology SC Nutrition & Dietetics; Physiology GA AI3KX UT WOS:000336761300001 PM 24885497 ER PT J AU Weiss, DJ Bhatt, S Mappin, B Van Boeckel, TP Smith, DL Hay, SI Gething, PW AF Weiss, Daniel J. Bhatt, Samir Mappin, Bonnie Van Boeckel, Thomas P. Smith, David L. Hay, Simon I. Gething, Peter W. TI Air temperature suitability for Plasmodium falciparum malaria transmission in Africa 2000-2012: a high-resolution spatiotemporal prediction SO MALARIA JOURNAL LA English DT Article DE Temperature suitability; Plasmodium falciparum; Africa ID SUB-SAHARAN AFRICA; ANOPHELES-GAMBIAE; SATELLITE IMAGERY; AQUATIC STAGES; CLIMATE; MODEL; RISK; EVAPOTRANSPIRATION; POPULATIONS; CULICIDAE AB Background: Temperature suitability for malaria transmission is a useful predictor variable for spatial models of malaria infection prevalence. Existing continental or global models, however, are synoptic in nature and so do not characterize inter-annual variability in seasonal patterns of temperature suitability, reducing their utility for predicting malaria risk. Methods: A malaria Temperature Suitability Index (TSI) was created by first modeling minimum and maximum air temperature with an eight-day temporal resolution from gap-filled MODerate Resolution Imaging Spectroradiometer (MODIS) daytime and night-time Land Surface Temperature (LST) datasets. An improved version of an existing biological model for malaria temperature suitability was then applied to the resulting temperature information for a 13-year data series. The mechanism underlying this biological model is simulation of emergent mosquito cohorts on a two-hour time-step and tracking of each cohort throughout its life to quantify the impact air temperature has on both mosquito survival and sporozoite development. Results: The results of this research consist of 154 monthly raster surfaces that characterize spatiotemporal patterns in TSI across Africa from April 2000 through December 2012 at a 1 km spatial resolution. Generalized TSI patterns were as expected, with consistently high values in equatorial rain forests, seasonally variable values in tropical savannas (wet and dry) and montane areas, and low values in arid, subtropical regions. Comparisons with synoptic approaches demonstrated the additional information available within the dynamic TSI dataset that is lost in equivalent synoptic products derived from long-term monthly averages. Conclusions: The dynamic TSI dataset presented here provides a new product with far richer spatial and temporal information than any other presently available for Africa. As spatiotemporal malaria modeling endeavors evolve, dynamic predictor variables such as the malaria temperature suitability data developed here will be essential for the rational assessment of changing patterns of malaria risk. C1 [Weiss, Daniel J.; Bhatt, Samir; Mappin, Bonnie; Hay, Simon I.; Gething, Peter W.] Univ Oxford, Dept Zool, Spatial Ecol & Epidemiol Grp, Oxford OX1 3PS, England. [Smith, David L.] Johns Hopkins Bloomberg Sch Publ Hlth, Malaria Res Inst, Baltimore, MD USA. [Smith, David L.] Johns Hopkins Bloomberg Sch Publ Hlth, Dept Epidemiol, Baltimore, MD USA. [Van Boeckel, Thomas P.] Princeton Univ, Dept Ecol & Evolutionary Biol, Princeton, NJ 08544 USA. [Smith, David L.; Hay, Simon I.] NIH, Fogarty Int Ctr, Bethesda, MD 20892 USA. RP Weiss, DJ (reprint author), Univ Oxford, Dept Zool, Spatial Ecol & Epidemiol Grp, Tinbergen Bldg,S Parks Rd, Oxford OX1 3PS, England. EM daniel.weiss@zoo.ox.ac.uk RI Hay, Simon/F-8967-2015; Smith, David/L-8850-2013; OI Gething, Peter/0000-0001-6759-5449; Hay, Simon/0000-0002-0611-7272; Smith, David/0000-0003-4367-3849; Mappin, Bonnie/0000-0002-1205-719X FU Bill and Melinda Gates Foundation [OPP1068048]; NIH/NIAID [U19AI089674]; Bloomberg Family Foundation; Senior Research Fellowship from the Wellcome Trust [095066]; RAPIDD program of the Science & Technology Directorate, Department of Homeland Security; Fogarty International Center, National Institutes of Health FX We thank David Benz for his assistance in handling the MODIS data and Ursula Dalrymple for proof reading this manuscript. PWG is a Medical Research Council Career Development Fellow (# K00669X) and receives support from the Bill and Melinda Gates Foundation (# OPP1068048) that also supports DJW, SB and BJM. DLS acknowledges funding from NIH/NIAID (U19AI089674) and the Bloomberg Family Foundation. SIH is funded by a Senior Research Fellowship from the Wellcome Trust (# 095066) and 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 45 TC 10 Z9 10 U1 2 U2 11 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1475-2875 J9 MALARIA J JI Malar. J. PD MAY 3 PY 2014 VL 13 AR 171 DI 10.1186/1475-2875-13-171 PG 11 WC Infectious Diseases; Parasitology; Tropical Medicine SC Infectious Diseases; Parasitology; Tropical Medicine GA AI4DL UT WOS:000336815700001 PM 24886586 ER PT J AU Jahrling, PB Tomori, O AF Jahrling, Peter B. Tomori, Owale TI Variola virus archives: a new century, a new approach SO LANCET LA English DT Editorial Material C1 [Jahrling, Peter B.] NIAID, NIH, Ft Detrick, MD 21702 USA. [Tomori, Owale] Redeemers Univ, Redemption City, Ogin State, Nigeria. RP Jahrling, PB (reprint author), NIAID, NIH, Ft Detrick, MD 21702 USA. EM jahrlingp@niaid.nih.gov NR 9 TC 2 Z9 2 U1 0 U2 8 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 MAY 3 PY 2014 VL 383 IS 9928 BP 1525 EP 1526 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA AG5YO UT WOS:000335495400005 PM 24792843 ER PT J AU Carafoli, E Klee, CB Lennarz, W AF Carafoli, Ernesto Klee, Claude B. Lennarz, William TI Malcolm Daniel Lane SO BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS LA English DT Biographical-Item C1 [Carafoli, Ernesto] Univ Padua, Dipartimento Chim Biol, Padua, Italy. [Klee, Claude B.] NCI, Biochem Lab, NIH, Bethesda, MD 20892 USA. [Lennarz, William] SUNY Stony Brook, Dept Biochem & Cell Biol, Stony Brook, NY 11794 USA. RP Carafoli, E (reprint author), Univ Padua, Dipartimento Chim Biol, Padua, Italy. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0006-291X EI 1090-2104 J9 BIOCHEM BIOPH RES CO JI Biochem. Biophys. Res. Commun. PD MAY 2 PY 2014 VL 447 IS 2 BP 223 EP 223 DI 10.1016/j.bbrc.2014.04.094 PG 1 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA AI0BJ UT WOS:000336510900001 ER PT J AU Oboti, L Perez-Gomez, A Keller, M Jacobi, E Birnbaumer, L Leinders-Zufall, T Zufall, F Chamero, P AF Oboti, Livio Perez-Gomez, Anabel Keller, Matthieu Jacobi, Eric Birnbaumer, Lutz Leinders-Zufall, Trese Zufall, Frank Chamero, Pablo TI A wide range of pheromone-stimulated sexual and reproductive behaviors in female mice depend on G protein Gao SO BMC BIOLOGY LA English DT Article DE Bruce effect; Estrus induction; Gao signaling; Lordosis; Mate recognition; Puberty acceleration; Reproduction ID ACCESSORY OLFACTORY-BULB; MALE-MOUSE URINE; VOMERONASAL RECEPTOR NEURONS; G-ALPHA-O; AGGRESSIVE-BEHAVIOR; SENSORY NEURONS; SYNTHETIC ANALOGS; MULTIGENE FAMILY; MUTANT MICE; ORGAN AB Background: Optimal reproductive fitness is essential for the biological success and survival of species. The vomeronasal organ is strongly implicated in the display of sexual and reproductive behaviors in female mice, yet the roles that apical and basal vomeronasal neuron populations play in controlling these gender-specific behaviors remain largely unclear. Results: To dissect the neural pathways underlying these functions, we genetically inactivated the basal vomeronasal organ layer using conditional, cell-specific ablation of the G protein Gao. Female mice mutant for Gao show severe alterations in sexual and reproductive behaviors, timing of puberty onset, and estrous cycle. These mutant mice are insensitive to reproductive facilitation stimulated by male pheromones that accelerate puberty and induce ovulation. Gao-mutant females exhibit a striking reduction in sexual receptivity or lordosis behavior to males, but gender discrimination seems to be intact. These mice also show a loss in male scent preference, which requires a learned association for volatile olfactory signals with other nonvolatile ownership signals that are contained in the high molecular weight fraction of male urine. Thus, Gao impacts on both instinctive and learned social responses to pheromones. Conclusions: These results highlight that sensory neurons of the Gao-expressing vomeronasal subsystem, together with the receptors they express and the molecular cues they detect, control a wide range of fundamental mating and reproductive behaviors in female mice. C1 [Oboti, Livio; Perez-Gomez, Anabel; Jacobi, Eric; Leinders-Zufall, Trese; Zufall, Frank; Chamero, Pablo] Univ Saarland, Dept Physiol, Sch Med, D-66421 Homburg, Germany. [Keller, Matthieu] Univ Tours, Lab Physiol Reprod & Comportments, CNRS, UMR 7247,INRA, F-37380 Nouzilly, France. [Birnbaumer, Lutz] NIEHS, Neurobiol Lab, Res Triangle Pk, NC 27709 USA. RP Zufall, F (reprint author), Univ Saarland, Dept Physiol, Sch Med, D-66421 Homburg, Germany. EM frank.zufall@uks.eu; pablo.chamero@uks.eu RI Perez-Gomez, Anabel/B-1888-2015; Oboti, Livio/P-5876-2015; Leinders-Zufall, Trese/B-4103-2009; OI Perez-Gomez, Anabel/0000-0001-9477-731X; Oboti, Livio/0000-0001-7197-568X; Leinders-Zufall, Trese/0000-0002-0678-362X; Chamero, Pablo/0000-0002-4305-1073; Keller, Matthieu/0000-0002-5445-7431 FU Deutsche Forschungsgemeinschaft [CH 920/2-1, SFB 894/A17, SFB 894/A16]; Intramural Research Program of the NIH [Z01 ES-101643]; Volkswagen Foundation; French Agence Nationale de la Recherche (Pherosex grant); DFG-funded International Graduate Program [GK1326] FX We thank Peter Mombaerts and Ulrich Boehm for supplying OMP-Cre mice and eR26-tGFP reporter mice, respectively, and Martina Pyrski for help with genotyping. This work was supported by grants from the Deutsche Forschungsgemeinschaft to PC (CH 920/2-1), FZ (SFB 894/A17) and TL-Z (SFB 894/A16), the Intramural Research Program of the NIH to LB (Project Z01 ES-101643), Volkswagen Foundation to TL-Z and the French Agence Nationale de la Recherche (Pherosex grant) to MK. EJ was supported by the DFG-funded International Graduate Program GK1326. TL-Z is a Lichtenberg Professor of the Volkswagen Foundation. NR 69 TC 17 Z9 17 U1 2 U2 24 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 MAY 2 PY 2014 VL 12 AR 31 DI 10.1186/1741-7007-12-31 PG 17 WC Biology SC Life Sciences & Biomedicine - Other Topics GA AI4CI UT WOS:000336812800001 PM 24886577 ER PT J AU Timsit, YE Negishi, M AF Timsit, Yoav E. Negishi, Masahiko TI Coordinated Regulation of Nuclear Receptor CAR by CCRP/DNAJC7, HSP70 and the Ubiquitin-Proteasome System SO PLOS ONE LA English DT Article ID CONSTITUTIVE ACTIVE/ANDROSTANE RECEPTOR; HEAT-SHOCK PROTEINS; HEPG2 CELLS; MOUSE-LIVER; ANDROSTANE RECEPTOR; SYNERGISTIC ACTIVATION; MOLECULAR CHAPERONES; PRIMARY HEPATOCYTES; GENE-TRANSCRIPTION; ESTROGEN-RECEPTOR AB The constitutive active/androstane receptor (CAR) plays an important role as a coordinate transcription factor in the regulation of various hepatic metabolic pathways for chemicals such as drugs, glucose, fatty acids, bilirubin, and bile acids. Currently, it is known that in its inactive state, CAR is retained in the cytoplasm in a protein complex with HSP90 and the tetratricopeptide repeat protein cytosoplasmic CAR retention protein (CCRP). Upon activation by phenobarbital (PB) or the PB-like inducer 1,4-bis[2-(3,5-dichloropyridyloxy)]-benzene (TCPOBOP), CAR translocates into the nucleus. We have identified two new components to the cytoplasmic regulation of CAR: ubiquitin-dependent degradation of CCRP and protein-protein interaction with HSP70. Treatment with the proteasome inhibitor MG132 (5 mu M) causes CAR to accumulate in the cytoplasm of transfected HepG2 cells. In the presence of MG132, TCPOBOP increases CCRP ubiquitination in HepG2 cells co-expressing CAR, while CAR ubiquitination was not detected. MG132 treatment of HepG2 also attenuated of TCPOBOP-induced CAR transcriptional activation on reporter constructs which contain CAR-binding DNA elements derived from the human CYP2B6 gene. The elevation of cytoplasmic CAR protein with MG132 correlated with an increase of HSP70, and to a lesser extent HSP60. Both CCRP and CAR were found to interact with endogenous HSP70 in HepG2 cells by immunoprecipitation analysis. Induction of HSP70 levels by heat shock also increased cytoplasmic CAR levels, similar to the effect of MG132. Lastly, heat shock attenuated TCPOBOP-induced CAR transcriptional activation, also similar to the effect of MG132. Collectively, these data suggest that ubiquitin-proteasomal regulation of CCRP and HSP70 are important contributors to the regulation of cytoplasmic CAR levels, and hence the ability of CAR to respond to PB or PB-like inducers. C1 [Timsit, Yoav E.; Negishi, Masahiko] Natl Inst Environm Hlth Sci, Pharmacogenet Sect, Lab Reprod & Dev Toxicol, NIH, Res Triangle Pk, NC 27709 USA. RP Negishi, M (reprint author), Natl Inst Environm Hlth Sci, Pharmacogenet Sect, Lab Reprod & Dev Toxicol, NIH, Res Triangle Pk, NC 27709 USA. EM negishi@niehs.nih.gov FU NIH [Z01ES1005-01] FX NIH Intramural Reseach program:: Z01ES1005-01. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 56 TC 5 Z9 5 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 MAY 2 PY 2014 VL 9 IS 5 AR e96092 DI 10.1371/journal.pone.0096092 PG 12 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA AI1ZS UT WOS:000336655700056 PM 24789201 ER PT J AU Marshall, KE Offerdahl, DK Speare, JO Dorward, DW Hasenkrug, A Carmody, AB Baron, GS AF Marshall, Karen E. Offerdahl, Danielle K. Speare, Jonathan O. Dorward, David W. Hasenkrug, Aaron Carmody, Aaron B. Baron, Gerald S. TI Glycosylphosphatidylinositol Anchoring Directs the Assembly of Sup35NM Protein into Non-fibrillar, Membrane-bound Aggregates SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article DE Amyloid; Electron Microscopy (EM); Glycosylphosphatidylinositol Anchors; Prions; Protein Aggregation; Protein Misfolding; Protein Self-assembly ID SCRAPIE PRION PROTEIN; STRAUSSLER-SCHEINKER DISEASE; YEAST PRION; IN-VIVO; ALZHEIMERS-DISEASE; AMYLOID DEPOSITS; SACCHAROMYCES-CEREVISIAE; NEUROBLASTOMA-CELLS; ELECTRON-MICROSCOPY; BETA-AMYLOIDOSIS AB Background: Sup35NM is a soluble protein that when misfolded forms amyloid fibril aggregates. Results: When tethered to membranes via a lipid anchor, Sup35NM aggregates adopt a non-fibrillar, membrane-bound structure. Conclusion: Lipid anchor-directed membrane association prevents assembly into fibrils. Significance: This may explain differences between prion diseases compared with related protein aggregation diseases because only prion diseases involve aggregation of a lipid-anchored protein. In prion-infected hosts, PrPSc usually accumulates as non-fibrillar, membrane-bound aggregates. Glycosylphosphatidylinositol (GPI) anchor-directed membrane association appears to be an important factor controlling the biophysical properties of PrPSc aggregates. To determine whether GPI anchoring can similarly modulate the assembly of other amyloid-forming proteins, neuronal cell lines were generated that expressed a GPI-anchored form of a model amyloidogenic protein, the NM domain of the yeast prion protein Sup35 (Sup35(GPI)). We recently reported that GPI anchoring facilitated the induction of Sup35(GPI) prions in this system. Here, we report the ultrastructural characterization of self-propagating Sup35(GPI) aggregates of either spontaneous or induced origin. Like membrane-bound PrPSc, Sup35(GPI) aggregates resisted release from cells treated with phosphatidylinositol-specific phospholipase C. Sup35(GPI) aggregates of spontaneous origin were detergent-insoluble, protease-resistant, and self-propagating, in a manner similar to that reported for recombinant Sup35NM amyloid fibrils and induced Sup35(GPI) aggregates. However, GPI-anchored Sup35 aggregates were not stained with amyloid-binding dyes, such as Thioflavin T. This was consistent with ultrastructural analyses, which showed that the aggregates corresponded to dense cell surface accumulations of membrane vesicle-like structures and were not fibrillar. Together, these results showed that GPI anchoring directs the assembly of Sup35NM into non-fibrillar, membrane-bound aggregates that resemble PrPSc, raising the possibility that GPI anchor-dependent modulation of protein aggregation might occur with other amyloidogenic proteins. This may contribute to differences in pathogenesis and pathology between prion diseases, which uniquely involve aggregation of a GPI-anchored protein, versus other protein misfolding diseases. C1 [Marshall, Karen E.; Offerdahl, Danielle K.; Speare, Jonathan O.; Dorward, David W.; Hasenkrug, Aaron; Carmody, Aaron B.; Baron, Gerald S.] NIAID, Persistent Viral Dis Lab, Rocky Mt Labs, NIH, Hamilton, MT 59840 USA. RP Baron, GS (reprint author), 903 S 4th St, Hamilton, MT 59840 USA. EM gbaron@niaid.nih.gov FU National Institutes of Health, NIAID, Intramural Research Program FX This work was supported, in whole or in part, by the National Institutes of Health, NIAID, Intramural Research Program. NR 89 TC 3 Z9 3 U1 1 U2 8 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 MAY 2 PY 2014 VL 289 IS 18 BP 12245 EP 12263 DI 10.1074/jbc.M114.556639 PG 19 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA AG7ER UT WOS:000335581400006 PM 24627481 ER PT J AU Yu, SL Levi, L Casadesus, G Kunos, G Noy, N AF Yu, Shuiliang Levi, Liraz Casadesus, Gemma Kunos, George Noy, Noa TI Fatty Acid-binding Protein 5 (FABP5) Regulates Cognitive Function Both by Decreasing Anandamide Levels and by Activating the Nuclear Receptor Peroxisome Proliferatoractivated Receptor beta/delta(PPAR beta/delta) in the Brain SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article DE Arachidonic Acid; Endocannabinoids; Lipids; Lipid-binding Protein; Peroxisome Proliferator-activated Receptor (PPAR) ID RETINOIC ACID; ENDOCANNABINOID SYSTEM; CANNABINOID RECEPTOR; HIPPOCAMPAL NEUROGENESIS; SIGNAL-TRANSDUCTION; INSULIN-RESISTANCE; MEMORY; ALPHA; MICE; CB1 AB Background: FABP5 shuttles ligands to the nuclear receptor PPAR/ and enhances degradation of the endocannabinoid anandamide. Results: Brain level of anandamide is high and PPAR/ activation is low in FABP5-null mice. These mice display impaired learning and memory. Conclusion: FABP5 regulates learning and memory by two distinct mechanisms. Significance: The data suggest that FABP5 may be a novel target for therapy of cognitive dysfunction. Endocannabinoids modulate multiple behaviors, including learning and memory. We show that the endocannabinoid anandamide (AEA) can alter neuronal cell function both through its established role in activation of the G-protein-coupled receptor CB1, and by serving as a precursor for a potent agonist of the nuclear receptor PPAR/, in turn up-regulating multiple cognition-associated genes. We show further that the fatty acid-binding protein FABP5 controls both of these functions in vivo. FABP5 both promotes the hydrolysis of AEA into arachidonic acid and thus reduces brain endocannabinoid levels, and directly shuttles arachidonic acid to the nucleus where it delivers it to PPAR/, enabling its activation. In accordance, ablation of FABP5 in mice results in excess accumulation of AEA, abolishes PPAR/ activation in the brain, and markedly impairs hippocampus-based learning and memory. The data indicate that, by controlling anandamide disposition and activities, FABP5 plays a key role in regulating hippocampal cognitive function. C1 [Yu, Shuiliang; Levi, Liraz; Noy, Noa] Case Western Reserve Univ, Dept Pharmacol, Sch Med, Cleveland, OH 44106 USA. [Casadesus, Gemma] Case Western Reserve Univ, Dept Neurosci, Sch Med, Cleveland, OH 44106 USA. [Noy, Noa] Case Western Reserve Univ, Dept Nutr, Sch Med, Cleveland, OH 44106 USA. [Kunos, George] NIAAA, Lab Physiol Studies, NIH, Bethesda, MD 20892 USA. RP Noy, N (reprint author), Case Western Reserve Univ, Dept Pharmacol, Sch Med, 10900 Euclid Ave W333, Cleveland, OH 44106 USA. EM noa.noy@case.edu FU National Institutes of Health [R01 DK060684] FX This work was supported, in whole or in part, by National Institutes of Health Grant R01 DK060684 (to N. N.). NR 54 TC 21 Z9 21 U1 0 U2 10 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 EI 1083-351X J9 J BIOL CHEM JI J. Biol. Chem. PD MAY 2 PY 2014 VL 289 IS 18 BP 12748 EP 12758 DI 10.1074/jbc.M114.559062 PG 11 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA AG7ER UT WOS:000335581400045 PM 24644281 ER PT J AU Hartman, KG Vitolo, MI Pierce, AD Fox, JM Shapiro, P Martin, SS Wilder, PT Weber, DJ AF Hartman, Kira G. Vitolo, Michele I. Pierce, Adam D. Fox, Jennifer M. Shapiro, Paul Martin, Stuart S. Wilder, Paul T. Weber, David J. TI Complex Formation between S100B Protein and the p90 Ribosomal S6 Kinase ( RSK) in Malignant Melanoma Is Calcium-dependent and Inhibits Extracellular Signalregulated Kinase ( ERK)-mediated Phosphorylation of RSK SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article DE Calcium; Calcium Binding Proteins; Cancer; ERK; MAP Kinases (MAPKs); Melanoma; RSK; S100 Proteins ID MAGNETIC-RESONANCE-SPECTROSCOPY; GLYCATION END-PRODUCTS; BINDING PROTEIN; WILD-TYPE; P53; S100B(BETA-BETA); ACTIVATION; RECEPTOR; CANCER; FAMILY AB Background: S100B is overexpressed in malignant melanoma and contributes to cancer progression. Results: The S100B-RSK complex was found to be Ca2+-dependent, block phosphorylation of RSK at Thr-573, and sequester RSK to the cytosol. Conclusion: The Ca2+-dependent S100B-RSK complex provides a new link between the MAPK and Ca2+ signaling pathways. Significance: S100B inhibitors may restore normal MAPK and Ca2+ signaling in malignant melanoma. S100B is a prognostic marker for malignant melanoma. Increasing S100B levels are predictive of advancing disease stage, increased recurrence, and low overall survival in malignant melanoma patients. Using S100B overexpression and shRNA(S100B) knockdown studies in melanoma cell lines, elevated S100B was found to enhance cell viability and modulate MAPK signaling by binding directly to the p90 ribosomal S6 kinase (RSK). S100B-RSK complex formation was shown to be Ca2+-dependent and to block ERK-dependent phosphorylation of RSK, at Thr-573, in its C-terminal kinase domain. Additionally, the overexpression of S100B sequesters RSK into the cytosol and prevents it from acting on nuclear targets. Thus, elevated S100B contributes to abnormal ERK/RSK signaling and increased cell survival in malignant melanoma. C1 [Pierce, Adam D.; Wilder, Paul T.; Weber, David J.] Univ Maryland, Dept Biochem & Mol Biol, Sch Med, Baltimore, MD 21201 USA. [Hartman, Kira G.; Fox, Jennifer M.; Martin, Stuart S.; Weber, David J.] Univ Maryland, Program Mol Med, Grad Program Life Sci, Baltimore, MD 21201 USA. [Vitolo, Michele I.; Martin, Stuart S.; Wilder, Paul T.] Univ Maryland, Dept Physiol, Sch Med, Baltimore, MD 21201 USA. [Pierce, Adam D.; Weber, David J.] Univ Maryland, Ctr Biomol Therapeut, Sch Med, Baltimore, MD 21201 USA. [Shapiro, Paul] Univ Maryland, Dept Pharmaceut Sci, Sch Pharm, Baltimore, MD 21201 USA. [Vitolo, Michele I.; Shapiro, Paul; Martin, Stuart S.; Wilder, Paul T.; Weber, David J.] Univ Maryland, Baltimore, MD 21201 USA. [Vitolo, Michele I.; Shapiro, Paul; Martin, Stuart S.; Wilder, Paul T.; Weber, David J.] Stewart Greenebaum NCI Canc Ctr, Baltimore, MD 21201 USA. [Fox, Jennifer M.] Univ Maryland, Ctr Stem Cell Biol & Regenerat Med, Dept Pediat, Sch Med, Baltimore, MD 21201 USA. RP Wilder, PT (reprint author), Dept Biochem & Mol Biol, 108 N Greene St, Baltimore, MD 21201 USA. EM pwild001@umaryland.edu; dweber@som.umaryland.edu FU National Institutes of Health [GM58888, CA107331, CA166576] FX This works was supported, in whole or in part, by National Institutes of Health grants GM58888 and CA107331 (to D.J.W.) and CA166576 (to M.I.V.). NR 64 TC 9 Z9 9 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 MAY 2 PY 2014 VL 289 IS 18 BP 12886 EP 12895 DI 10.1074/jbc.M114.561613 PG 10 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA AG7ER UT WOS:000335581400057 PM 24627490 ER PT J AU Kamnaksh, A Budde, MD Kovesdi, E Long, JB Frank, JA Agoston, DV AF Kamnaksh, Alaa Budde, Matthew D. Kovesdi, Erzsebet Long, Joseph B. Frank, Joseph A. Agoston, Denes V. TI Diffusion Tensor Imaging Reveals Acute Subcortical Changes after Mild Blast-Induced Traumatic Brain Injury SO SCIENTIFIC REPORTS LA English DT Article ID LONG-TERM CONSEQUENCES; AXONAL INJURY; MILITARY; CONCUSSION; BIOMARKERS; VETERANS; COMBAT; MODEL; RATS; MRI AB Mild blast-induced traumatic brain injury (mbTBI) poses special diagnostic challenges due to its overlapping symptomatology with other neuropsychiatric conditions and the lack of objective outcome measures. Diffusion tensor imaging (DTI) can potentially provide clinically relevant information toward a differential diagnosis. In this study, we aimed to determine if single and repeated (5 total; administered on consecutive days) mild blast overpressure exposure results in detectable structural changes in the brain, especially in the hippocampus. Fixed rat brains were analyzed by ex vivo DTI at 2 h and 42 days after blast (or sham) exposure(s). An anatomy-based region of interest analysis revealed significant interactions in axial and radial diffusivity in a number of subcortical structures at 2 h only. Differences between single-and multiple-injured rats were largely in the thalamus but not the hippocampus. Our findings demonstrate the value and the limitations of DTI in providing a better understanding of mbTBI pathobiology. C1 [Kamnaksh, Alaa; Agoston, Denes V.] Uniformed Serv Univ Hlth Sci, Dept Anat Physiol & Genet, Bethesda, MD 20814 USA. [Kamnaksh, Alaa] Uniformed Serv Univ Hlth Sci, Ctr Neurosci & Regenerat Med, Bethesda, MD 20814 USA. [Budde, Matthew D.; Frank, Joseph A.] Natl Inst Biomed Imaging & Bioengn, NIH, Bethesda, MD 20892 USA. [Kovesdi, Erzsebet] US Dept Vet Affairs, Vet Affairs Cent Off, Washington, DC 20420 USA. [Long, Joseph B.] Walter Reed Army Inst Res, Ctr Mil Psychiat & Neurosci, Blast Induced Neurotrauma Branch, Silver Spring, MD 20910 USA. RP Agoston, DV (reprint author), Uniformed Serv Univ Hlth Sci, Dept Anat Physiol & Genet, 4301 Jones Bridge Rd, Bethesda, MD 20814 USA. EM denes.agoston@usuhs.edu FU Center for Neuroscience and Regenerative Medicine [G1703F] FX We thank the Neurotrauma Team at the Walter Reed Army Institute of Research for their technical help during the exposures, along with Eric Gold and Lindsay Janes for assistance with the MRI experiments. This work was supported by the Center for Neuroscience and Regenerative Medicine grant number G1703F. NR 59 TC 6 Z9 7 U1 2 U2 12 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 MAY 2 PY 2014 VL 4 AR 4809 DI 10.1038/srep04809 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA AG1ZZ UT WOS:000335216000001 PM 24786839 ER PT J AU Zakirova, NF Karpenko, IL Prokofjeva, MM Vanpouille, C Prassolov, VS Shipitsyn, AV Kochetkov, SN AF Zakirova, N. F. Karpenko, I. L. Prokofjeva, M. M. Vanpouille, C. Prassolov, V. S. Shipitsyn, A. V. Kochetkov, S. N. TI Acyclovir phosphoramidates as potential anti-HIV drugs SO RUSSIAN CHEMICAL BULLETIN LA English DT Article DE acyclovir; phosphoramidates; human immunodeficiency virus ID DERIVATIVES; TECHNOLOGY AB A number of phosphoramidate derivatives of acyclovir (ACV) were obtained. These compounds revealed themselves as latent forms of acyclovir monophosphate (ACV-MP). The optimized route to the title phosphoramidates involves the synthesis of intermediate phosphorodichloridates followed by their treatment with various amines. The compounds obtained showed moderate antiviral activity both in vitro in a controlled system of secure screening for anti-HIV agents and in a tissue system enabling ex vivo determination of the efficiency of the drug and its effect on HIV replication in two weeks. C1 [Zakirova, N. F.; Karpenko, I. L.; Prokofjeva, M. M.; Prassolov, V. S.; Shipitsyn, A. V.; Kochetkov, S. N.] Russian Acad Sci, VA Engelhardt Mol Biol Inst, Moscow 119991, Russia. [Vanpouille, C.] NICHHD, NIH, Bethesda, MD 20892 USA. RP Shipitsyn, AV (reprint author), Russian Acad Sci, VA Engelhardt Mol Biol Inst, 32 Ul Vavilova, Moscow 119991, Russia. EM chip@email.ru RI Karpenko, Inna/F-5879-2015 OI Karpenko, Inna/0000-0001-9849-0447 FU Russian Foundation for Basic Research [13-04-00829-a, 12-04-00581-a]; Presidium of the Russian Academy of Sciences (Program "Molecular and Cell Biology") FX This work was financially supported by the Russian Foundation for Basic Research (Project Nos 13-04-00829-a and 12-04-00581-a) and the Presidium of the Russian Academy of Sciences (Program "Molecular and Cell Biology"). NR 13 TC 1 Z9 1 U1 0 U2 9 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1066-5285 EI 1573-9171 J9 RUSS CHEM B+ JI Russ. Chem. Bull. PD MAY PY 2014 VL 63 IS 5 BP 1192 EP 1196 PG 5 WC Chemistry, Multidisciplinary SC Chemistry GA CC1ZD UT WOS:000350143000025 ER PT J AU Song, HK Preiss, LR Maslen, CL Kroner, B Devereux, RB Roman, MJ Holmes, KW Tolunay, HE Desvigne-Nickens, P Asch, FM Milewski, RK Bavaria, J LeMaire, SA AF Song, Howard K. Preiss, Liliana R. Maslen, Cheryl L. Kroner, Barbara Devereux, Richard B. Roman, Mary J. Holmes, Kathryn W. Tolunay, H. Eser Desvigne-Nickens, Patrice Asch, Federico M. Milewski, Rita K. Bavaria, Joseph LeMaire, Scott A. CA GenTAC Consortium TI Valve-Sparing Aortic Root Replacement in Patients with Marfan Syndrome Enrolled in the National Registry of Genetically Triggered Thoracic Aortic Aneurysms and Cardiovascular Conditions SO JOURNAL OF HEART VALVE DISEASE LA English DT Article ID ASCENDING AORTA; SURGERY; INCOMPETENCE; EXPERIENCE; OPERATIONS; GENE AB Background and aim of the study: The long-term outcomes of aortic valve-sparing (AVS) root replacement in Marfan syndrome (MFS) patients remain uncertain. The study aim was to determine the utilization and outcomes of AVS root replacement in MFS patients enrolled in the Registry of Genetically Triggered Thoracic Aortic Aneurysms and Cardiovascular Conditions (GenTAC). Methods: At the time of this analysis, 788 patients with MFS were enrolled in the GenTAC Registry, of whom 288 had undergone aortic root replacement. Patients who had undergone AVS procedures were compared to those who had undergone aortic valve replacement (AVR). Results: AVS root replacement was performed in 43.5% of MFS patients, and the frequency of AVS was increased over the past five years. AVS patients were younger at the time of surgery (31.0 versus 36.3 years, p = 0.006) and more likely to have had elective rather than emergency surgery compared to AVR patients, in whom aortic valve dysfunction and aortic dissection was the more likely primary indication for surgery. After a mean follow up of 6.2 +/- 3.6 years, none of the 87 AVS patients had required reoperation; in contrast, after a mean follow up of 10.5 +/- 7.6 years, 11.5% of AVR patients required aortic root reoperation. Aortic valve function has been durable, with 95.8% of AVS patients having aortic insufficiency that was graded as mild or less. Conclusion: AVS root replacement is performed commonly among the MFS population, and the durability of the aortic repair and aortic valve function have been excellent to date. These results justify a continued use of the procedure in an elective setting. The GenTAC Registry will be a useful resource to assess the long-term durability of AVS root replacement in the future. C1 [Song, Howard K.] OHSU, Div Cardiothorac Surg, Portland, OR 97239 USA. [Preiss, Liliana R.; Kroner, Barbara] Oregon Hlth & Sci Univ, Div Cardiovasc Med, Portland, OR 97239 USA. [Maslen, Cheryl L.] Oregon Hlth & Sci Univ, Div Pediat Cardiol, Portland, OR 97239 USA. [Devereux, Richard B.; Roman, Mary J.] Res Triangle Inst Int, Bethesda, MD USA. [Holmes, Kathryn W.] Weill Cornell Med Coll, Div Cardiol, New York, NY USA. [Tolunay, H. Eser; Desvigne-Nickens, Patrice] NHLBI, Bethesda, MD 20892 USA. [Asch, Federico M.] MedStar Washington Hosp Ctr, Div Cardiol, Washington, DC USA. [Milewski, Rita K.; Bavaria, Joseph] Univ Penn, Med Ctr, Div Cardiothorac Surg, Philadelphia, PA 19104 USA. [LeMaire, Scott A.] Baylor Coll Med, Michael E DeBakey Dept Surg, Div Cardiothorac Surg, Houston, TX 77030 USA. RP Song, HK (reprint author), OHSU, Div Cardiothorac Surg, Mail Code L353,3181 SW Sam Jackson Pk Rd, Portland, OR 97239 USA. EM songh@ohsu.edu FU National Heart, Lung, and Blood Institute, National Institutes of Health, Department of Health and Human Services [HHSN268200648199C, HHSN268201000048C]; National Institute of Arthritis and Musculoskeletal and Skin Diseases; Oregon Clinical and Translational Research Institute (Portland, OR); National Center for Research Resources (Bethesda, MD) [UL1 RR024140]; Weill Cornell Medical College Clinical Translational Science Center (New York, NY) [UL1RR024996] FX The GenTAC Registry has been supported in full by Federal funds from the National Heart, Lung, and Blood Institute, National Institutes of Health, Department of Health and Human Services, under Contract Numbers HHSN268200648199C and HHSN268201000048C. Additional support was provided by the National Institute of Arthritis and Musculoskeletal and Skin Diseases, the Oregon Clinical and Translational Research Institute (Portland, OR), grant UL1 RR024140 from the National Center for Research Resources (Bethesda, MD), and by the Weill Cornell Medical College Clinical Translational Science Center (New York, NY), grant UL1RR024996. Stephen N. Palmer PhD, ELS contributed to the editing of the manuscript. NR 28 TC 2 Z9 2 U1 0 U2 3 PU I C R PUBLISHERS PI NORTHWOOD PA CRISPIN HOUSE, 12/A SOUTH APPROACH, MOOR PARK, NORTHWOOD HA6 2ET, ENGLAND SN 0966-8519 J9 J HEART VALVE DIS JI J. Heart Valve Dis. PD MAY PY 2014 VL 23 IS 3 BP 292 EP 298 PG 7 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA CB4BJ UT WOS:000349572900005 PM 25296451 ER PT J AU Saketkoo, LA Mittoo, S Huscher, D Khanna, D Dellaripa, PF Distler, O Flaherty, KR Frankel, S Oddis, CV Denton, CP Fischer, A Kowal-Bielecka, OM LeSage, D Merkel, PA Phillips, K Pittrow, D Swigris, J Antoniou, K Baughman, RP Castelino, FV Christmann, RB Christopher-Stine, L Collard, HR Cottin, V Danoff, S Highland, KB Hummers, L Shah, AA Kim, DS Lynch, DA Miller, FW Proudman, SM Richeldi, L Ryu, JH Sandorfi, N Sarver, C Wells, AU Strand, V Matteson, EL Brown, KK Seibold, JR AF Saketkoo, Lesley Ann Mittoo, Shikha Huscher, Doerte Khanna, Dinesh Dellaripa, Paul F. Distler, Oliver Flaherty, Kevin R. Frankel, Sid Oddis, Chester V. Denton, Christopher P. Fischer, Aryeh Kowal-Bielecka, Otylia M. LeSage, Daphne Merkel, Peter A. Phillips, Kristine Pittrow, David Swigris, Jeffrey Antoniou, Katerina Baughman, Robert P. Castelino, Flavia V. Christmann, Romy B. Christopher-Stine, Lisa Collard, Harold R. Cottin, Vincent Danoff, Sonye Highland, Kristin B. Hummers, Laura Shah, Ami A. Kim, Dong Soon Lynch, David A. Miller, Frederick W. Proudman, Susanna M. Richeldi, Luca Ryu, Jay H. Sandorfi, Nora Sarver, Catherine Wells, Athol U. Strand, Vibeke Matteson, Eric L. Brown, Kevin K. Seibold, James R. TI Connective tissue disease related interstitial lung diseases and idiopathic pulmonary fibrosis: provisional core sets of domains and instruments for use in clinical trials SO THORAX LA English DT Article ID GEORGES RESPIRATORY QUESTIONNAIRE; QUALITY-OF-LIFE; SYSTEMIC-SCLEROSIS; SCLERODERMA LUNG; END-POINT; VALIDITY; IPF; MORTALITY; COUGH; CYCLOPHOSPHAMIDE AB Rationale Clinical trial design in interstitial lung diseases (ILDs) has been hampered by lack of consensus on appropriate outcome measures for reliably assessing treatment response. In the setting of connective tissue diseases (CTDs), some measures of ILD disease activity and severity may be confounded by non-pulmonary comorbidities. Methods The Connective Tissue Disease associated Interstitial Lung Disease (CTD-ILD) working group of Outcome Measures in Rheumatology-a non-profit international organisation dedicated to consensus methodology in identification of outcome measures-conducted a series of investigations which included a Delphi process including >248 ILD medical experts as well as patient focus groups culminating in a nominal group panel of ILD experts and patients. The goal was to define and develop a consensus on the status of outcome measure candidates for use in randomised controlled trials in CTD-ILD and idiopathic pulmonary fibrosis (IPF). Results A core set comprising specific measures in the domains of lung physiology, lung imaging, survival, dyspnoea, cough and health-related quality of life is proposed as appropriate for consideration for use in a hypothetical 1-year multicentre clinical trial for either CTD-ILD or IPF. As many widely used instruments were found to lack full validation, an agenda for future research is proposed. Conclusion Identification of consensus preliminary domains and instruments to measure them was attained and is a major advance anticipated to facilitate multicentre RCTs in the field. C1 [Saketkoo, Lesley Ann] Louisiana State Univ, Hlth Sci Ctr, New Orleans, LA 70112 USA. [Mittoo, Shikha] Univ Toronto, Toronto, ON, Canada. [Huscher, Doerte] German Rheumatism Res Ctr, Berlin, Germany. [Huscher, Doerte] Charite, D-13353 Berlin, Germany. [Khanna, Dinesh; Flaherty, Kevin R.; Phillips, Kristine] Univ Michigan, Ann Arbor, MI 48109 USA. [Dellaripa, Paul F.] Brigham & Womens Hosp, Boston, MA 02115 USA. [Distler, Oliver] Univ Zurich Hosp, CH-8091 Zurich, Switzerland. [Frankel, Sid] Univ Manitoba, Winnipeg, MB R3T 2N2, Canada. [Oddis, Chester V.] Univ Pittsburgh, Pittsburgh, PA USA. [Denton, Christopher P.] Royal Free Hosp, London NW3 2QG, England. [Fischer, Aryeh; Swigris, Jeffrey; Lynch, David A.; Brown, Kevin K.] Natl Jewish Hlth, Denver, CO USA. [Kowal-Bielecka, Otylia M.] Med Univ Bialystok, Bialystok, Poland. [LeSage, Daphne] Patient Res Partner, Off Publ Hlth, New Orleans, LA USA. [Merkel, Peter A.; Sandorfi, Nora] Univ Penn, Philadelphia, PA 19104 USA. [Pittrow, David] Univ Dresden, Dresden, Germany. [Antoniou, Katerina] Univ Crete, Iraklion, Greece. [Baughman, Robert P.] Univ Cincinnati, Cincinnati, OH USA. [Castelino, Flavia V.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Christmann, Romy B.] Boston Univ, Sch Med, Boston, MA 02118 USA. [Christopher-Stine, Lisa; Danoff, Sonye; Hummers, Laura; Shah, Ami A.] Johns Hopkins Univ, Baltimore, MD USA. [Collard, Harold R.] Univ Calif San Francisco, San Francisco, CA 94143 USA. [Cottin, Vincent] Univ Lyon 1, F-69365 Lyon, France. [Highland, Kristin B.] Cleveland Clin, Cleveland, OH 44106 USA. [Kim, Dong Soon] Univ Ulsan, Asan Med Ctr, Ulsan 680749, South Korea. [Miller, Frederick W.] NIEHS, NIH, Bethesda, MD USA. [Proudman, Susanna M.] Univ Adelaide, Adelaide, SA, Australia. [Richeldi, Luca] Univ Southampton, Resp Biomed Res Unit, Southampton SO9 5NH, Hants, England. [Ryu, Jay H.; Matteson, Eric L.] Mayo Clin, Coll Med, Rochester, MN USA. [Sarver, Catherine] Patient Res Partner, Bethesda, MD USA. [Wells, Athol U.] Royal Brompton Hosp, London SW3 6LY, England. [Wells, Athol U.] Natl Heart & Lung Inst, London, England. [Strand, Vibeke] Stanford Univ, Palo Alto, CA 94304 USA. [Seibold, James R.] Scleroderma Res Consultants LLC, Avon, CT USA. RP Saketkoo, LA (reprint author), Louisiana State Univ, Hlth Sci Ctr New Orleans, LSU Scleroderma & Sarcoidosis Patient, Dept Med,Sect Rheumatol, 1542 Tulane Ave, New Orleans, LA 70112 USA. EM ctd.ild@gmail.com RI Keen, Kevin/D-5628-2013; Mittoo, Shikha/C-4616-2015; Baddini Martinez, Jose/E-3098-2012; Riemekasten, Gabriela/B-5019-2017; Kairalla, Ronaldo/D-5736-2014; OI Keen, Kevin/0000-0001-5695-0505; Kairalla, Ronaldo/0000-0001-7194-0479; Porter, Joanna/0000-0002-7307-169X; Miller, Frederick/0000-0003-2831-9593; Dixon, William/0000-0001-5881-4857 FU intramural division of the National Institute of Environmental Health Sciences, National Institutes of Health; Brigham and Women's Hospital; Charite Hospital-Berlin; German Rheumatism Research Centre; Ira J Fine Discovery Fund; Jonathan and Lisa Rye Scleroderma Research Foundation; Louisiana State University Health Sciences Center-New Orleans; Mayo Clinic-Rochester; National Jewish Hospital Denver; Louisiana State Office of Public Health-New Orleans; OMERACT (Outcome Measures in Rheumatology); Scleroderma Foundation; Sibley Hospital Foundation; Sonia Roth AARC Foundation; Abbott Laboratories Canada; Actelion; Boehringer-Ingelheim Pharmaceuticals; Celgene; Intermune; Sigma Tau; UCB; United Therapeutics FX Non-profit support: These studies were supported in part by the intramural division of the National Institute of Environmental Health Sciences, National Institutes of Health; and the following non-profit organisations: Brigham and Women's Hospital, Charite Hospital-Berlin, German Rheumatism Research Centre, Ira J Fine Discovery Fund, Jonathan and Lisa Rye Scleroderma Research Foundation, Louisiana State University Health Sciences Center-New Orleans, Mayo Clinic-Rochester, National Jewish Hospital Denver, Louisiana State Office of Public Health-New Orleans, OMERACT (Outcome Measures in Rheumatology), Scleroderma Foundation, Sibley Hospital Foundation, and Sonia Roth AARC Foundation. Commercial Interest Support: Abbott Laboratories Canada, Actelion, Boehringer-Ingelheim Pharmaceuticals, Celgene, Intermune, Sigma Tau, UCB and United Therapeutics. NR 41 TC 28 Z9 29 U1 2 U2 13 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 MAY PY 2014 VL 69 IS 5 BP 428 EP 436 DI 10.1136/thoraxjnl-2013-204202 PG 9 WC Respiratory System SC Respiratory System GA AY5ZW UT WOS:000347648600009 PM 24368713 ER PT J AU Bilic, E Grkovic, L Pulanic, D Seiwerth, RS Bilic, E Nemet, D Pavletic, SZ AF Bilic, E. Grkovic, L. Pulanic, D. Seiwerth, R. Serventi Bilic, E. Nemet, D. Pavletic, S. Z. TI Small fiber neuropathy in patients with chronic graft-versus-host disease after allogeneic hematopoietic stem cell transplantation: preliminary results of a prospective study SO JOURNAL OF NEUROLOGY LA English DT Meeting Abstract CT Joint Congress of European Neurology CY MAY 31-JUN 03, 2014 CL Istanbul, TURKEY SP European Federat Neurol Soc C1 [Bilic, E.] Univ Zagreb, Sch Med, Clin Hosp Ctr Zagreb, Dept Neurol, Zagreb 41001, Croatia. [Grkovic, L.; Pulanic, D.; Seiwerth, R. Serventi; Nemet, D.] Univ Zagreb, Sch Med, Clin Hosp Ctr Zagreb, Dept Hematol, Zagreb 41001, Croatia. [Bilic, E.] Univ Zagreb, Sch Med, Clin Hosp Ctr Zagreb, Dept Pediat Hematol & Oncol, Zagreb 41001, Croatia. [Pavletic, S. Z.] NCI, Expt Transplantat & Immunol Branch, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER HEIDELBERG PI HEIDELBERG PA TIERGARTENSTRASSE 17, D-69121 HEIDELBERG, GERMANY SN 0340-5354 EI 1432-1459 J9 J NEUROL JI J. Neurol. PD MAY PY 2014 VL 261 SU 1 MA PP1251 BP S312 EP S312 PG 1 WC Clinical Neurology SC Neurosciences & Neurology GA AY6KA UT WOS:000347674001044 ER PT J AU Vural, A Johnson, J Singleton, A Temucin, CM AF Vural, A. Johnson, J. Singleton, A. Temucin, C. M. TI Adult-onset case of Brown-Vialetto-Van-Laere syndrome with SLC52A3 mutation SO JOURNAL OF NEUROLOGY LA English DT Meeting Abstract CT Joint Congress of European Neurology CY MAY 31-JUN 03, 2014 CL Istanbul, TURKEY SP European Federat Neurol Soc C1 [Vural, A.] Besni Govt Hosp, Dept Neurol, Adiyaman, Turkey. [Johnson, J.; Singleton, A.] Natl Inst Ageing, Neurogenet Lab, NIH, Bethesda, MD USA. [Temucin, C. M.] Hacettepe Univ, Fac Med, Dept Neurol, TR-06100 Ankara, Turkey. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER HEIDELBERG PI HEIDELBERG PA TIERGARTENSTRASSE 17, D-69121 HEIDELBERG, GERMANY SN 0340-5354 EI 1432-1459 J9 J NEUROL JI J. Neurol. PD MAY PY 2014 VL 261 SU 1 MA PP4091 BP S426 EP S426 PG 1 WC Clinical Neurology SC Neurosciences & Neurology GA AY6KA UT WOS:000347674001320 ER PT J AU Warnke, C von Geldern, G Markwerth, P Dehmel, T Hoepner, R Gold, R Pawlita, M Kumpfel, T Maurer, M Stangel, M Wegner, F Hohlfeld, R Straeten, V Limmroth, V Weber, T Hermsen, D Kleinschnitz, C Hartung, HP Wattjes, MP Svenningson, A Major, E Olsson, T Kieseier, BC Adams, O AF Warnke, C. von Geldern, G. Markwerth, P. Dehmel, T. Hoepner, R. Gold, R. Pawlita, M. Kuempfel, T. Maeurer, M. Stangel, M. Wegner, F. Hohlfeld, R. Straeten, V. Limmroth, V. Weber, T. Hermsen, D. Kleinschnitz, C. Hartung, H. -P. Wattjes, M. P. Svenningson, A. Major, E. Olsson, T. Kieseier, B. C. Adams, O. TI The CSF JCV antibody index for diagnosis of natalizumab-associated PML SO JOURNAL OF NEUROLOGY LA English DT Meeting Abstract CT Joint Congress of European Neurology CY MAY 31-JUN 03, 2014 CL Istanbul, TURKEY SP European Federat Neurol Soc C1 [Warnke, C.; Markwerth, P.; Dehmel, T.; Hermsen, D.; Hartung, H. -P.; Kieseier, B. C.; Adams, O.] Univ Dusseldorf, Dusseldorf, Germany. [von Geldern, G.; Major, E.] NINDS, Bethesda, MD 20892 USA. [Hoepner, R.; Gold, R.] Ruhr Univ Bochum, St Josef Hosp, Bochum, Germany. [Pawlita, M.] German Canc Res Ctr, Heidelberg, Germany. [Kuempfel, T.; Hohlfeld, R.] Univ Munich, Munich, Germany. [Maeurer, M.] Caritas Hosp, Bad Mergentheim, Germany. [Stangel, M.; Wegner, F.] Hannover Med Sch MHH, Hannover, Germany. [Straeten, V.] Johannes Wesling Hosp Minden, Minden, Germany. [Limmroth, V.] Merheim Hosp, Cologne, Germany. [Weber, T.] Marienhospital, Hamburg, Germany. [Kleinschnitz, C.] Univ Wurzburg, D-97070 Wurzburg, Germany. [Wattjes, M. P.] Vrije Univ Amsterdam Med Ctr, Amsterdam, Netherlands. [Svenningson, A.] Umea Univ Hosp, S-90185 Umea, Sweden. [Olsson, T.] Karolinska Inst, Stockholm, Sweden. NR 0 TC 0 Z9 0 U1 1 U2 1 PU SPRINGER HEIDELBERG PI HEIDELBERG PA TIERGARTENSTRASSE 17, D-69121 HEIDELBERG, GERMANY SN 0340-5354 EI 1432-1459 J9 J NEUROL JI J. Neurol. PD MAY PY 2014 VL 261 SU 1 MA OS2124 BP S44 EP S45 PG 2 WC Clinical Neurology SC Neurosciences & Neurology GA AY6KA UT WOS:000347674000117 ER PT J AU Gipson, C Brown, P AF Gipson, Chester Brown, Patricia TI A word from USDA and OLAW SO LAB ANIMAL LA English DT Editorial Material C1 [Gipson, Chester] USDA, APHIS, AC, Washington, DC 20250 USA. [Brown, Patricia] NIH, OLAW, OER, OD,HHS, Bethesda, MD USA. RP Gipson, C (reprint author), USDA, APHIS, AC, Washington, DC 20250 USA. NR 3 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0093-7355 EI 1548-4475 J9 LAB ANIMAL JI Lab Anim. PD MAY PY 2014 VL 43 IS 5 BP 159 EP 159 PG 1 WC Veterinary Sciences SC Veterinary Sciences GA AZ2ZC UT WOS:000348096700014 PM 24751846 ER PT J AU Urquidez-Romero, R Esparza-Romero, J Chaudhari, LS Begay, RC Giraldo, M Ravussin, E Knowler, WC Hanson, RL Bennett, PH Schulz, LO Valencia, ME AF Urquidez-Romero, Rene Esparza-Romero, Julian Chaudhari, Lisa S. Begay, R. Cruz Giraldo, Mario Ravussin, Eric Knowler, William C. Hanson, Robert L. Bennett, Peter H. Schulz, Leslie O. Valencia, Mauro E. TI Study Design of the Maycoba Project: Obesity and Diabetes in Mexican Pimas SO AMERICAN JOURNAL OF HEALTH BEHAVIOR LA English DT Article DE type 2 diabetes; prevalence; environmental changes; Pima Indians ID DAILY ENERGY-EXPENDITURE; DOUBLY LABELED WATER; ENZYMATIC DETERMINATION; PHYSICAL-ACTIVITY; AMERICAN-INDIANS; LIFE-STYLE; ASSOCIATION; CHOLESTEROL; PREVALENCE; IDENTIFICATION AB Objective: To focus on the rationale and methods of the Maycoba Project. Methods: Study population included Mexican Pima Indians (MPI) and Blancos aged >= 20-years, living in the village of Maycoba and surrounding area. Surveys in 1995 and 2010 included a medical history, biochemical and anthropometric measurements. Additionally, socioeconomic, physical activity, and dietary interviews were conducted. The 2010 study incorporated investigations on type 2 diabetes (T2D) and obesity-associated genetic alleles and human-environment changes. Results: The study results are limited to demographic data and description of the eligible and examined sample. Conclusions: This study may yield important information on T2D and obesity etiology in a traditional population exposed to environmental changes. C1 [Urquidez-Romero, Rene] Univ Autonoma Ciudad Juarez, Dept Ciencias Salud, Inst Ciencias Biomed, Ciudad Juarez, Chihuahua, Mexico. [Esparza-Romero, Julian; Valencia, Mauro E.] Ctr Invest Alimentac & Desarrollo, Dept Nutr Publ & Salud, Ac Hermosillo, Sonora, Mexico. [Chaudhari, Lisa S.; Begay, R. Cruz; Schulz, Leslie O.] No Arizona Univ, Coll Hlth & Human Serv, Flagstaff, AZ 86011 USA. [Giraldo, Mario] Calif State Univ Northridge, Dept Geog, Northridge, CA 91330 USA. [Ravussin, Eric] Pennington Biomed Res Ctr, Baton Rouge, LA 70808 USA. [Knowler, William C.; Hanson, Robert L.; Bennett, Peter H.] NIDDK, Phoenix Epidemiol & Clin Res Branch, NIH, Phoenix, AZ USA. RP Valencia, ME (reprint author), Ctr Invest Alimentac & Desarrollo, Dept Nutr Publ & Salud, Ac Hermosillo, Sonora, Mexico. EM mauro@ciad.mx FU NIDDK NIH HHS [R01 DK082568, 1R01DK082568-01A1, P30 DK072476] NR 38 TC 2 Z9 2 U1 0 U2 6 PU PNG PUBLICATIONS PI OAK RIDGE PA 2205-K OAK RIDGE RD, #115, OAK RIDGE, NC 27310 USA SN 1945-7359 J9 AM J HEALTH BEHAV JI Am. J. Health Behav. PD MAY PY 2014 VL 38 IS 3 BP 370 EP 378 DI 10.5993/AJHB.38.3.6 PG 9 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA AS1JB UT WOS:000344036300006 PM 24636033 ER PT J AU Logan, J Kim, SW Pareto, D Telang, F Wang, GJ Fowler, JS Biegon, A AF Logan, Jean Kim, Sung Won Pareto, Deborah Telang, Frank Wang, Gene-Jack Fowler, Joanna S. Biegon, Anat TI Kinetic Analysis of [C-11]Vorozole Binding in the Human Brain with Positron Emission Tomography SO MOLECULAR IMAGING LA English DT Article ID MONOAMINE-OXIDASE-A; IN-VIVO; AROMATASE INHIBITOR; PET; BOLUS; CYTOCHROME-P450; INFUSION; SMOKING; POTENT; RAT AB Using positron emission tomography, we investigated the kinetics of [C-11]vorozole ([C-11]VOR), a radiotracer for the enzyme aromatase that catalyzes the last step in estrogen biosynthesis. Six subjects were scanned under baseline conditions followed by retest 2 weeks later. The retest was followed by a blocking study with 2.5 mg of the aromatase inhibitor letrozole. The binding potential (BPNDA) was estimated from a Lassen plot using the total tissue distribution volume (V-T) for baseline and blocked. BPNDA for the thalamus was found to be 15 times higher than that for the cerebellum. From the letrozole studies, we found that [C-11]VOR exhibits a slow binding compartment (small k(4)) that has a nonspecific and a blockable component. Because of the sensitivity of V-T to variations in k(4), a common value was used for the four highest binding regions. We also considered the tissue uptake to plasma ratio for 60 to 90 minutes as an outcome measure. Using the ratio method, the difference between the highest and lowest was 2.4 compared to 3.5 for the V-T. The ratio method underestimates the high regions but is less variable and may be more suitable for patient studies. Because of its kinetics and distribution, this tracer is not a candidate for a bolus infusion or reference tissue methods. C1 [Logan, Jean] Brookhaven Natl Lab, Dept Biosci, Upton, NY 11973 USA. NIAAA, Bethesda, MD USA. Hosp Valle De Hebron, Magnet Resonance Unit, Barcelona, Spain. CIBER BBN, Zaragoza, Spain. Mt Sinai Sch Med, Dept Psychiat, New York, NY USA. SUNY Stony Brook, Dept Chem, Stony Brook, NY 11794 USA. SUNY Stony Brook, Sch Med, Dept Neurol, Stony Brook, NY 11794 USA. RP Logan, J (reprint author), Brookhaven Natl Lab, Dept Biosci, Upton, NY 11973 USA. EM jean.logan@nyumc.org FU [1R21EB012707] FX Financial disclosure of authors: This study was supported by grant 1R21EB012707 (Anat Biegon PI). NR 41 TC 0 Z9 0 U1 1 U2 2 PU B C DECKER INC PI HAMILTON PA 69 JOHN STREET SOUTH, STE 310, HAMILTON, ONTARIO L8N 2B9, CANADA SN 1535-3508 EI 1536-0121 J9 MOL IMAGING JI Mol. Imaging PD MAY PY 2014 VL 13 IS 3 DI 10.2310/7290.2014.00004 PG 12 WC Biochemical Research Methods; Radiology, Nuclear Medicine & Medical Imaging SC Biochemistry & Molecular Biology; Radiology, Nuclear Medicine & Medical Imaging GA AS4AF UT WOS:000344215300003 ER PT J AU Farrell, MM La Porta, M Gallagher, A Vinson, C Bernal, SB AF Farrell, Margaret M. La Porta, Madeline Gallagher, Alissa Vinson, Cynthia Bernal, Sarah Bruce TI Research to Reality: Moving Evidence Into Practice Through an Online Community of Practice SO PREVENTING CHRONIC DISEASE LA English DT Article ID CANCER CONTROL; PARTNERSHIP; TRANSLATION; HEALTH AB How can a community of practice help further the practical application of cancer control research? In 2011, the National Cancer Institute (NCI) launched an online community of practice, Research to Reality (R2R). R2R aims to infuse evidence-based strategies into communities by engaging researchers and practitioners in a joint approach to research dissemination. To measure community growth and engagement, NCI measures data across 3 program domains: content, interaction, and activity. NCI uses Web analytics, usability testing, and content analyses to manage and evaluate R2R. As of December 2013, R2R had more than 1,700 registered members. More than 500 researchers and practitioners register for the monthly cyber-seminars, and 40% return each month. R2R hosts more than 15,500 page views and 5,000 site visits in an average month. This article describes the process of convening this online community and quantifies our experiences to date. C1 [Farrell, Margaret M.; La Porta, Madeline; Gallagher, Alissa; Vinson, Cynthia] NCI, Bethesda, MD 20892 USA. [Bernal, Sarah Bruce] ICF Int, Fairfax, VA USA. RP Farrell, MM (reprint author), NCI, 9609 Med Ctr Dr,Room 4E444, Bethesda, MD 20892 USA. EM farrellm@mail.nih.gov NR 20 TC 1 Z9 1 U1 1 U2 10 PU CENTERS DISEASE CONTROL PI ATLANTA PA 1600 CLIFTON RD, ATLANTA, GA 30333 USA SN 1545-1151 J9 PREV CHRONIC DIS JI Prev. Chronic Dis. PD MAY PY 2014 VL 11 AR 130272 DI 10.5888/pcd11.130272 PG 6 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA AR3XH UT WOS:000343522000008 ER PT J AU Wells, SA Santoro, M AF Wells, Samuel A., Jr. Santoro, Massimo TI Update: The Status of Clinical Trials With Kinase Inhibitors in Thyroid Cancer SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article ID PHASE-II TRIAL; CHRONIC MYELOID-LEUKEMIA; LYMPH-NODE METASTASES; PPAR-GAMMA AGONIST; ACQUIRED-RESISTANCE; COLORECTAL-CANCER; UNITED-STATES; PHOSPHATIDYLINOSITOL 3-KINASE/AKT; RET/PTC REARRANGEMENTS; PROGRESSIVE MEDULLARY AB Context: Thyroid cancer is usually cured by timely thyroidectomy; however, the treatment of patients with advanced disease is challenging because their tumors are mostly unresponsive to conventional therapies. Recently, the malignancy has attracted much interest for two reasons: the dramatic increase in its incidence over the last three decades, and the discovery of the genetic mutations or chromosomal rearrangements causing most histological types of thyroid cancer. Objective: This update reviews the molecular genetics of thyroid cancer and the clinical trials evaluating kinase inhibitors (KIs) in patients with locally advanced or metastatic disease. The update also reviews studies in other malignancies, which have identified mechanisms of efficacy, and also resistance, to specific KIs. This information has been critical both to the development of effective second-generation drugs and to the design of combinatorial therapeutic regimens. Finally, the update addresses the major challenges facing clinicians who seek to develop more effective therapy for patients with thyroid cancer. Results: PubMed was searched from January 2000 to November 2013 using the following terms: thyroid cancer, treatment of thyroid cancer, clinical trials in thyroid cancer, small molecule therapeutics, kinase inhibitors, and next generation sequencing. Conclusions: A new era in cancer therapy has emerged based on the introduction of KIs for the treatment of patients with liquid and solid organ malignancies. Patients with thyroid cancer have benefited from this advance and will continue to do so with the development of drugs having greater specificity and with the implementation of clinical trials of combined therapeutics to overcome drug resistance. C1 [Wells, Samuel A., Jr.] NCI, Canc Genet Branch, Bethesda, MD 20892 USA. [Santoro, Massimo] Univ Naples Federico II, Dipartimento Med Mol & Biotecnol Med, I-80131 Naples, Italy. RP Wells, SA (reprint author), NCI, Canc Genet Branch, Bldg 37,Room 1-1A106,Convent Dr, Bethesda, MD 20892 USA. EM wellss@mail.nih.gov FU AstraZeneca PLC; Roche FX S.A.W. has nothing to declare. M.S. has received research support from AstraZeneca PLC, and Roche. He has also participated in a collaborative study with Ariad Pharmaceuticals, Inc. NR 141 TC 16 Z9 16 U1 0 U2 3 PU ENDOCRINE SOC PI WASHINGTON PA 2055 L ST NW, SUITE 600, WASHINGTON, DC 20036 USA SN 0021-972X EI 1945-7197 J9 J CLIN ENDOCR METAB JI J. Clin. Endocrinol. Metab. PD MAY PY 2014 VL 99 IS 5 BP 1543 EP 1555 DI 10.1210/jc.2013-2622 PG 13 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA AP8PB UT WOS:000342339800034 PM 24423326 ER PT J AU Sklavos, MM Giri, N Stratton, P Alter, BP Pinto, LA AF Sklavos, Martha M. Giri, Neelam Stratton, Pamela Alter, Blanche P. Pinto, Ligia A. TI Anti-Mullerian Hormone Deficiency in Females With Fanconi Anemia SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article ID PRIMARY OVARIAN INSUFFICIENCY; MENSTRUAL-CYCLE; RESERVE; CANCER; PREGNANCY; FAILURE; MARKER; COHORT; RISK; AMH AB Context: In females with Fanconi anemia (FA), infertility is often accompanied by diminished ovarian reserve and hypergonadotropic amenorrhea before the age of 30 years, suggesting primary ovarian insufficiency (POI). POI is typically diagnosed only after perimenopausal symptoms are observed. Objective: The objective of the study was to assess whether serum anti-Mullerian hormone (AMH) levels can serve as a cycle-independent marker for the diagnosis of POI in patients with FA. Design and Setting: This observational study used the National Cancer Institute's inherited bone marrow failure syndrome cohort at the National Institutes of Health Clinical Center. Participants: The study included 22 females with FA, 20 unaffected female relatives of patients with FA, and 21 unrelated healthy females under 41 years of age. Main Outcome Measure: Serum AMH, a marker of ovarian reserve, was measured in all participants. Results: Females with FA had very low AMH levels (median 0.05 ng/mL; range 0-2.32 ng/mL; P < .01) when compared with unaffected relatives (median 2.10 ng/mL; range 0.04-4.73 ng/mL) and unrelated healthy females (median 1.92 ng/mL; range 0.31-6.64 ng/mL). All patients with FA older than 25 years of age were diagnosed with POI and had undetectable AMH levels. Conclusions: AMH deficiency appears to be a shared trait across this heterogeneous FA cohort. Substantially reduced AMH levels in females with FA suggest a primary ovarian defect associated with reduced fertility. Measurement of AMH at the time of FA diagnosis and subsequent monitoring of AMH levels at regular intervals may be useful for the timely management of complications related to POI such as subfertility/infertility, osteoporosis, and menopausal symptoms. C1 [Sklavos, Martha M.; Pinto, Ligia A.] Leidos Biomed Res Inc, Frederick Natl Lab Canc Res, Human Papillomavirus Immunol Lab, Frederick, MD 21702 USA. [Giri, Neelam; Alter, Blanche P.] NCI, Clin Genet Branch, Div Canc Epidemiol & Genet, Dept Hlth & Human Serv, Bethesda, MD 20892 USA. [Giri, Neelam; Alter, Blanche P.] NCI, Clin Genet Branch, Div Canc Epidemiol & Genet, NIH,Dept Hlth & Human Serv, Bethesda, MD 20892 USA. [Stratton, Pamela] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Program Reprod & Adult Endocrinol, Bethesda, MD 20814 USA. RP Pinto, LA (reprint author), Leidos Biomed Res Inc, Human Papillomavirus Immunol Lab, Bldg 469,Room 111,1050 Boyles St, Frederick, MD 21702 USA. EM pintol@mail.nih.gov FU Fanconi Anemia Research Fund; Intramural Research Program of the National Institutes of Health and the National Cancer Institute; Westat, Inc. [N02CP-91026, N02-CP-11019, HHSN261200655001C]; National Cancer Institute, National Institutes of Health [HHSN261200800001E] FX This work was supported in part by a research grant from Fanconi Anemia Research Fund(fanconi.org) (to N.G.); the Intramural Research Program of the National Institutes of Health and the National Cancer Institute (to B.P.A. and N.G.); and by contracts N02CP-91026, N02-CP-11019, and HHSN261200655001C with Westat, Inc. This project has been funded in whole or in part with federal funds from the National Cancer Institute, National Institutes of Health, under Contract HHSN261200800001E. NR 31 TC 4 Z9 4 U1 1 U2 4 PU ENDOCRINE SOC PI WASHINGTON PA 2055 L ST NW, SUITE 600, WASHINGTON, DC 20036 USA SN 0021-972X EI 1945-7197 J9 J CLIN ENDOCR METAB JI J. Clin. Endocrinol. Metab. PD MAY PY 2014 VL 99 IS 5 BP 1608 EP 1614 DI 10.1210/jc.2013-3559 PG 7 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA AP8PB UT WOS:000342339800042 PM 24438373 ER PT J AU Bible, KC Suman, VJ Molina, JR Smallridge, RC Maples, WJ Menefee, ME Rubin, J Karlin, N Sideras, K Morris, JC Mclver, B Hay, I Fatourechi, V Burton, JK Webster, KP Bieber, C Traynor, AM Flynn, PJ Goh, BC Isham, CR Harris, P Erlichman, C AF Bible, Keith C. Suman, Vera J. Molina, Julian R. Smallridge, Robert C. Maples, William J. Menefee, Michael E. Rubin, Joseph Karlin, Nina Sideras, Kostandinos Morris, John C., III Mclver, Bryan Hay, Ian Fatourechi, Vahab Burton, Jill K. Webster, Kevin P. Bieber, Carolyn Traynor, Anne M. Flynn, Patrick J. Goh, Boon Cher Isham, Crescent R. Harris, Pamela Erlichman, Charles CA Endocrine Malignancies Disease Ori Mayo Clinic Cancer Ctr Mayo Phase 2 Consortium TI A Multicenter Phase 2 Trial of Pazopanib in Metastatic and Progressive Medullary Thyroid Carcinoma: MC057H SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article ID ALTERNATING COMBINATION; CANCER; EFFICACY; SORAFENIB; SUNITINIB AB Context: Pazopanib is a small molecule inhibitor of kinases principally including vascular endothelial growth factor receptors-1, -2, and -3; platelet-derived growth factor receptors-alpha and -beta; and c-Kit. We previously reported a tumor response rate of 49% in patients with advanced differentiated thyroid cancer and 0% in patients with advanced anaplastic thyroid cancer. The present report details results of pazopanib therapy in advanced medullary thyroid cancer (MTC). Objective, Design, Setting, Patients, Intervention, and Outcome Measures: Having noted preclinical activity of pazopanib in MTC, patients with advanced MTC who had disease progression within the preceding 6 months were accrued to this multiinstitutional phase II clinical trial to assess tumor response rate (by Response Evaluation Criteria In Solid Tumors criteria) and safety of pazopanib given orally once daily at 800 mg until disease progression or intolerability. Results: From September 22, 2008, to December 11, 2011, 35 individuals (80% males, median age 60 y) were enrolled. All patients have been followed up until treatment discontinuation or for a minimum of four cycles. Eight patients (23%) are still on the study treatment. The median number of therapy cycles was eight. Five patients attained partial Response Evaluation Criteria In Solid Tumors responses (14.3%; 90% confidence interval 5.8%-27.7%), with a median progression-free survival and overall survival of 9.4 and 19.9 months, respectively. Side effects included treatment-requiring (new) hypertension (33%), fatigue (14%), diarrhea (9%), and abnormal liver tests (6%); 3 of 35 patients (8.6%) discontinued therapy due to adverse events. There was one death of a study patient after withdrawal from the trial deemed potentially treatment related. Conclusions: Pazopanib has promising clinical activity in metastatic MTC with overall manageable toxicities. C1 [Bible, Keith C.; Molina, Julian R.; Rubin, Joseph; Sideras, Kostandinos; Burton, Jill K.; Webster, Kevin P.; Isham, Crescent R.; Erlichman, Charles] Mayo Clin, Div Med Oncol, Rochester, MN 55905 USA. [Suman, Vera J.] Mayo Clin, Div Biomed Stat & Informat, Rochester, MN 55905 USA. [Morris, John C., III; Mclver, Bryan; Hay, Ian; Fatourechi, Vahab] Mayo Clin, Div Endocrinol, Rochester, MN 55905 USA. [Smallridge, Robert C.] Mayo Clin Florida, Div Endocrinol, Jacksonville, FL 32224 USA. [Maples, William J.; Menefee, Michael E.; Bieber, Carolyn] Mayo Clin Florida, Div Med Oncol, Jacksonville, FL 32224 USA. [Karlin, Nina] Mayo Clin Arizona, Div Med Oncol, Scottsdale, AZ 85259 USA. [Traynor, Anne M.] Univ Wisconsin, Carbone Canc Ctr, Madison, WI 53705 USA. [Flynn, Patrick J.] Minnesota Oncol Hematol, Minneapolis, MN 55407 USA. [Goh, Boon Cher] Natl Univ Singapore Hosp, Singapore 119228, Singapore. [Harris, Pamela] Natl Canc Inst, Canc Therapy Evaluat Program, Bethesda, MD 20892 USA. RP Bible, KC (reprint author), Div Med Oncol, 200 First St SW, Rochester, MN 55901 USA. EM bible.keith@mayo.edu FU National Cancer Institute [CA15083, CM62205] FX This work was supported by National Cancer Institute Grants CA15083 and CM62205. NR 15 TC 23 Z9 24 U1 0 U2 2 PU ENDOCRINE SOC PI WASHINGTON PA 2055 L ST NW, SUITE 600, WASHINGTON, DC 20036 USA SN 0021-972X EI 1945-7197 J9 J CLIN ENDOCR METAB JI J. Clin. Endocrinol. Metab. PD MAY PY 2014 VL 99 IS 5 BP 1687 EP 1693 DI 10.1210/jc.2013-3713 PG 7 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA AP8PB UT WOS:000342339800051 PM 24606083 ER PT J AU Billings, LK Jablonski, KA Ackerman, RJ Taylor, A Fanelli, RR McAteer, JB Guiducci, C Delahanty, LM Dabelea, D Kahn, SE Franks, PW Hanson, RL Maruthur, NM Shuldiner, AR Mayer-Davis, EJ Knowler, WC Florez, JC AF Billings, Liana K. Jablonski, Kathleen A. Ackerman, Rachel J. Taylor, Andrew Fanelli, Rebecca R. McAteer, Jarred B. Guiducci, Candace Delahanty, Linda M. Dabelea, Dana Kahn, Steven E. Franks, Paul W. Hanson, Robert L. Maruthur, Nisa M. Shuldiner, Alan R. Mayer-Davis, Elizabeth J. Knowler, William C. Florez, Jose C. CA Diab Prevention Program Res Grp TI The Influence of Rare Genetic Variation in SLC30A8 on Diabetes Incidence and beta-Cell Function SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article ID ZINC TRANSPORTER ZNT8; PREVENTION PROGRAM; INSULIN-SECRETION; LIFE-STYLE; BASE-LINE; GLUCOSE; ASSOCIATION; INTERVENTION; METFORMIN; VARIANTS AB Context/Objective: The variant rs13266634 in SLC30A8, encoding a beta-cell-specific zinc transporter, is associated with type 2 diabetes. We aimed to identify other variants in SLC30A8 that increase diabetes risk and impair beta-cell function, and test whether zinc intake modifies this risk. Design/Outcome: We sequenced exons in SLC30A8 in 380 Diabetes Prevention Program (DPP) participants and identified 44 novel variants, which were genotyped in 3445 DPP participants and tested for association with diabetes incidence and measures of insulin secretion and processing. We examined individual common variants and used gene burden tests to test 39 rare variants in aggregate. Results: We detected a near-nominal association between a rare-variant genotype risk score and diabetes risk. Five common variants were associated with the oral disposition index. Various methods aggregating rare variants demonstrated associations with changes in oral disposition index and insulinogenic index during year 1 of follow-up. We did not find a clear interaction of zinc intake with genotype on diabetes incidence. Conclusions: Individual common and an aggregate of rare genetic variation in SLC30A8 are associated with measures of beta-cell function in the DPP. Exploring rare variation may complement ongoing efforts to uncover the genetic influences that underlie complex diseases. C1 [Billings, Liana K.; Ackerman, Rachel J.; Taylor, Andrew; Fanelli, Rebecca R.; McAteer, Jarred B.; Florez, Jose C.] Massachusetts Gen Hosp, Dept Med, Ctr Human Genet Res, Boston, MA 02114 USA. [Billings, Liana K.; Delahanty, Linda M.; Florez, Jose C.] Massachusetts Gen Hosp, Dept Med, Diabet Res Ctr, Diabet Unit, Boston, MA 02114 USA. [Billings, Liana K.; Delahanty, Linda M.; Florez, Jose C.] Harvard Univ, Sch Med, Dept Med, Boston, MA 02115 USA. [Franks, Paul W.] Harvard Univ, Sch Publ Hlth, Dept Nutr, Boston, MA 02115 USA. [Billings, Liana K.] NorthShore Univ HealthSyst, Dept Med, Evanston, IL 60201 USA. [Billings, Liana K.] Univ Chicago, Pritzker Sch Med, Chicago, IL 60637 USA. [Jablonski, Kathleen A.] George Washington Univ, Ctr Biostat, Rockville, MD 20852 USA. [Taylor, Andrew; McAteer, Jarred B.; Guiducci, Candace; Florez, Jose C.] Broad Inst, Program Med & Populat Genet, Cambridge, MA 02142 USA. [Dabelea, Dana] Univ Colorado, Colorado Sch Publ Hlth, Dept Epidemiol, Denver, CO 80045 USA. [Kahn, Steven E.] VA Puget Sound Hlth Care Syst, Div Metab Endocrinol & Nutr, Seattle, WA 98108 USA. Univ Washington, Seattle, WA 98108 USA. [Franks, Paul W.] Lund Univ, Genet & Mol Epidemiol Unit, Dept Clin Sci, SE-20041 Malmo, Sweden. [Hanson, Robert L.; Knowler, William C.] NIDDK, Diabet Epidemiol & Clin Res Sect, NIH, Phoenix, AZ 85014 USA. [Maruthur, Nisa M.] Johns Hopkins Univ, Sch Med, Div Gen Internal Med, Dept Med, Baltimore, MD 21205 USA. [Shuldiner, Alan R.] Univ Maryland, Sch Med, Div Endocrinol Diabet & Nutr, Dept Med, Baltimore, MD 21201 USA. [Mayer-Davis, Elizabeth J.] Univ N Carolina, Gillings Sch Global Publ Hlth, Dept Nutr, Chapel Hill, NC 27599 USA. RP Florez, JC (reprint author), Massachusetts Gen Hosp, 185 Cambridge St,Simches Res Bldg CPZN 5-250, Boston, MA 02114 USA. EM dppmail@biostat.bsc.gwu.edu FU National Institutes of Health (NIH)/National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) [R01 DK072041]; NIH/NIDDK at the DPP Data Coordinating Center in George Washington University [U01 DK048489]; NIH Office of Dietary Supplements; NRSA Institutional Training Grant [T32 DK007028-35]; Endocrine Society's Lilly Scholar's Award; NIH Loan Repayment Award; NIDDK [1 L30 DK089944-01]; Doris Duke Charitable Foundation; NorthShore Auxiliary Research Scholar Award; Department of Veterans Affairs; NIDDK of the NIH; NIDDK; Indian Health Service; Office of Research on Minority Health; National Institute of Child Health and Human Development; National Institute on Aging; Centers for Disease Control and Prevention; Office of Research on Women's Health; American Diabetes Association FX This work was supported by National Institutes of Health (NIH)/National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) Grant R01 DK072041 to J.C.F., K.A.J., and A.R.S. and a subcontract from NIH/NIDDK U01 DK048489 at the DPP Data Coordinating Center in George Washington University to J.C.F., facilitated by a targeted grant from the NIH Office of Dietary Supplements. During the course of this study, L.K.B. was supported by NRSA Institutional Training Grant T32 DK007028-35 to the Massachusetts General Hospital, the Endocrine Society's Lilly Scholar's Award, NIH Loan Repayment Award, NIDDK 1 L30 DK089944-01, Harvard Catalyst, a Distinguished Clinical Scientist Award to David Altshuler from the Doris Duke Charitable Foundation, and the NorthShore Auxiliary Research Scholar Award. S.E.K. is supported in part by the Department of Veterans Affairs.; The NIDDK of the NIH provided funding to the clinical centers and the Coordinating Center for the design and conduct of the study and collection, management, analysis, and interpretation of the data. The Southwestern American Indian Centers were supported directly by the NIDDK and the Indian Health Service. The General Clinical Research Center Program, National Center for Research Resources, supported data collection at many of the clinical centers. Funding for data collection and participant support was also provided by the Office of Research on Minority Health, the National Institute of Child Health and Human Development, the National Institute on Aging, the Centers for Disease Control and Prevention, the Office of Research on Women's Health, the Department of Veterans Affairs, and the American Diabetes Association. Bristol-Myers Squibb and Parke-Davis provided medication. This research was also supported, in part, by the intramural research program of the NIDDK. LifeScan Inc, Health O Meter, Hoechst Marion Roussel, Inc, Merck-Medco Managed Care, Inc, Merck and Co, Nike Sports Marketing, Slim Fast Foods Co, and Quaker Oats Co donated materials, equipment, or medicines for concomitant conditions. McKesson BioServices Corp, Matthews Media Group, Inc, and the Henry M. Jackson Foundation provided support services under subcontract with the Coordinating Center. The opinions expressed are those of the investigators and do not necessarily reflect the views of the Indian Health Service or other funding agencies. A complete list of centers, investigators, and staff can be found in the Supplemental Appendix. NR 19 TC 6 Z9 6 U1 0 U2 0 PU ENDOCRINE SOC PI WASHINGTON PA 2055 L ST NW, SUITE 600, WASHINGTON, DC 20036 USA SN 0021-972X EI 1945-7197 J9 J CLIN ENDOCR METAB JI J. Clin. Endocrinol. Metab. PD MAY PY 2014 VL 99 IS 5 BP E926 EP E930 DI 10.1210/jc.2013-2378 PG 5 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA AP8PB UT WOS:000342339800025 PM 24471563 ER PT J AU Bram, Z Xekouki, P Louiset, E Keil, MF Avgeropoulos, D Giatzakis, C Nesterova, M Sinaii, N Hofland, LJ Cherqaoui, R Lefebvre, H Stratakis, CA AF Bram, Zakariae Xekouki, Paraskevi Louiset, Estelle Keil, Meg F. Avgeropoulos, Dimitrios Giatzakis, Christoforos Nesterova, Maria Sinaii, Ninet Hofland, Leo J. Cherqaoui, Rabia Lefebvre, Herve Stratakis, Constantine A. TI Does Somatostatin Have a Role in the Regulation of Cortisol Secretion in Primary Pigmented Nodular Adrenocortical Disease (PPNAD)? A Clinical and in Vitro Investigation SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article ID GASTRIC-INHIBITORY POLYPEPTIDE; CUSHINGS-SYNDROME; RECEPTOR SUBTYPES; CARNEY COMPLEX; GLUCOCORTICOID-RECEPTOR; NEUROENDOCRINE TUMORS; MEDICAL-TREATMENT; GENE-EXPRESSION; ADRENAL-TUMORS; DEXAMETHASONE AB Context: Somatostatin (SST) receptors (SSTRs) are expressed in a number of tissues, including the adrenal cortex, but their role in cortisol secretion has not been well characterized. Objectives: The objective of the study was to investigate the expression of SSTRs in the adrenal cortex and cultured adrenocortical cells from primary pigmented nodular adrenocortical disease (PPNAD) tissues and to test the effect of a single injection of 100 mu g of the SST analog octreotide on cortisol secretion in patients with PPNAD. Setting and Design: The study was conducted at an academic research laboratory and clinical research center. Expression of SSTRs was examined in 26 PPNAD tissues and the immortalized PPNAD cell line CAR47. Ten subjects with PPNAD underwent a randomized, single-blind, crossover study of their cortisol secretion every 30 minutes over 12 hours (6:00 PM to 6:00 AM) before and after the midnight administration of octreotide 100 mu g sc. Methods: SSTRs expression was investigated by quantitative PCR and immunohistochemistry. The CAR47 and primary cell lines were studied in vitro. The data of the 10 patients were analyzed before and after the administration of octreotide. Results: All SSTRs, especially SSTR1-3, were expressed in PPNAD at significantly higher levels than in normal adrenal. SST was found to differentially regulate expression of its own receptors in the CAR47 cell line. However, the administration of octreotide to patients with PPNAD did not significantly affect cortisol secretion. Conclusions: SSTRs are overexpressed in PPNAD tissues in comparison with normal adrenal cortex. Octreotide did not exert any significant effect on cortisol secretion in a short clinical pilot study in a small number of patients with PPNAD, but long-acting SST analogs targeting multiple SSTRs may be worth investigating in this condition. C1 [Bram, Zakariae; Louiset, Estelle; Lefebvre, Herve] Univ Rouen, Inst Res & Innovat Biomed, Lab Neuronal & Neuroendocrine Differentiat & Comm, INSERM U982, F-76821 Rouen, France. [Xekouki, Paraskevi; Avgeropoulos, Dimitrios; Giatzakis, Christoforos; Nesterova, Maria; Cherqaoui, Rabia; Stratakis, Constantine A.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Program Dev Endocrinol & Genet, NIH, Sect Endocrinol & Genet, Bethesda, MD 20892 USA. [Keil, Meg F.; Stratakis, Constantine A.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Program Dev Endocrinol & Genet, Pediat Endocrinol Inter Inst Training Program, NIH, Bethesda, MD 20892 USA. [Sinaii, Ninet] NICHHD, NIH, Ctr Clin, Bethesda, MD 20892 USA. NIH, Bethesda, MD 20892 USA. [Hofland, Leo J.] Erasmus MC, NL-3015 GE Rotterdam, Netherlands. [Lefebvre, Herve] Univ Hosp Rouen, Inst Res & Innovat Biomed, Dept Endocrinol, F-76031 Rouen, France. RP Stratakis, CA (reprint author), Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Sect Endocrinol & Genet, Program Dev Endocrinol & Genet, NIH, Bldg 10,CRC,Room 1-3330,10 Ctr Dr,MSC1103, Bethesda, MD 20892 USA. EM stratakc@mail.nih.gov FU National Institutes of Health Intramural Research Program of the Eunice Kennedy Shriver National Institute of Child Health and Human Development; Agence Nationale de la Recherche and Societe Francaise d'Endocrinologie FX This work was supported by the National Institutes of Health Intramural Research Program of the Eunice Kennedy Shriver National Institute of Child Health and Human Development. Z.B. was the recipient of grants from Agence Nationale de la Recherche and Societe Francaise d'Endocrinologie. NR 36 TC 1 Z9 1 U1 0 U2 2 PU ENDOCRINE SOC PI WASHINGTON PA 2055 L ST NW, SUITE 600, WASHINGTON, DC 20036 USA SN 0021-972X EI 1945-7197 J9 J CLIN ENDOCR METAB JI J. Clin. Endocrinol. Metab. PD MAY PY 2014 VL 99 IS 5 BP E891 EP E901 DI 10.1210/jc.2013-2657 PG 11 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA AP8PB UT WOS:000342339800021 PM 24512486 ER PT J AU Nicolaides, NC Roberts, ML Kino, T Braatvedt, G Hurt, DE Katsantoni, E Sertedaki, A Chrousos, GP Charmandari, E AF Nicolaides, Nicolas C. Roberts, Michael L. Kino, Tomoshige Braatvedt, Geoffrey Hurt, Darrell E. Katsantoni, Eleni Sertedaki, Amalia Chrousos, George P. Charmandari, Evangelia TI A Novel Point Mutation of the Human Glucocorticoid Receptor Gene Causes Primary Generalized Glucocorticoid Resistance Through Impaired Interaction With the LXXLL Motif of the p160 Coactivators: Dissociation of the Transactivating and Transreppressive Activities SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article ID LIGAND-BINDING DOMAIN; STRESS-RESPONSE; DISEASE; GR AB Context: Primary generalized glucocorticoid resistance is a rare genetic disorder characterized by generalized, partial, target-tissue insensitivity to glucocorticoids. The molecular basis of the condition has been ascribed to inactivating mutations in the human glucocorticoid receptor (hGR) gene. Objective: The objective of the study was to present three new cases caused by a novel mutation in the hGR gene and to delineate the molecular mechanisms through which the mutant receptor impairs glucocorticoid signal transduction. Design and Results: The index case (father) and his two daughters presented with increased urinary free cortisol excretion and resistance of the hypothalamic-pituitary-adrenal axis to dexamethasone suppression in the absence of clinical manifestations suggestive of Cushing syndrome. All subjects harbored a novel, heterozygous, point mutation (T -> G) at nucleotide position 1724 of the hGR gene, which resulted in substitution of valine by glycine at amino acid 575 of the receptor. Compared with the wild-type receptor, the hGR alpha V575G demonstrated a significant (33%) reduction in its ability to transactivate the mouse mammary tumor virus promoter in response to dexamethasone, a 50% decrease in its affinity for the ligand, and a 2.5-fold delay in nuclear translocation. Although it did not exert a dominant negative effect on the wild-type receptor and preserved its ability to bind to DNA, hGR alpha V575G displayed significantly enhanced (similar to 80%) ability to transrepress the nuclear factor-kappa B signaling pathway. Finally, the mutant receptor hGR alpha V575G demonstrated impaired interaction with the LXXLL motif of the glucocorticoid receptor-interacting protein 1 coactivator in vitro and in computer-based structural simulation via its defective activation function-2 (AF-2) domain. Conclusions: The natural mutant receptor hGR alpha V575G causes primary generalized glucocorticoid resistance by affecting multiple steps in the glucocorticoid signaling cascade, including the affinity for the ligand, the time required for nuclear translocation, and the interaction with the glucocorticoid-interacting protein-1 coactivator. C1 [Nicolaides, Nicolas C.; Roberts, Michael L.; Sertedaki, Amalia; Chrousos, George P.; Charmandari, Evangelia] Univ Athens, Sch Med, Aghia Sophia Childrens Hosp, Dept Pediat 1,Div Endocrinol Metab & Diabet, Athens 11527, Greece. [Nicolaides, Nicolas C.; Roberts, Michael L.; Sertedaki, Amalia; Chrousos, George P.; Charmandari, Evangelia] Acad Athens, Biomed Res Fdn, Clin Res Ctr, Div Endocrinol & Metab, Athens 11527, Greece. [Katsantoni, Eleni] Acad Athens, Biomed Res Fdn, Clin Res Ctr, Div Hematol, Athens 11527, Greece. [Kino, Tomoshige] NIAID, Off Cyber Infrastructure & Computat Biol, NIH, Unit Mol Hormone Action, Bethesda, MD 20892 USA. [Hurt, Darrell E.] NIAID, Off Cyber Infrastructure & Computat Biol, NIH, Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Bethesda, MD 20892 USA. [Braatvedt, Geoffrey] Univ Auckland, Dept Med, Auckland 1142, New Zealand. RP Charmandari, E (reprint author), Univ Athens, Sch Med, Aghia Sophia Childrens Hosp, Dept Pediat 1,Div Endocrinol Metab & Diabet, Thivon & Papadiamantopoulou St, Athens 11527, Greece. EM evangelia.charmandari@googlemail.com RI Charmandari, Evangelia/B-6701-2011 FU European Union (European Social Fund); Greek national funds through the Operational Program "Education and Lifelong Learning" of the National Strategic Reference Framework, Research Funding Program, THALIS, University of Athens, Athens, Greece; Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, Maryland; National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland FX This work was supported by the European Union (European Social Fund) and Greek national funds through the Operational Program "Education and Lifelong Learning" of the National Strategic Reference Framework, Research Funding Program, THALIS, University of Athens, Athens, Greece; the intramural program of the Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, Maryland 20892; and the National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland. NR 19 TC 11 Z9 11 U1 0 U2 6 PU ENDOCRINE SOC PI WASHINGTON PA 2055 L ST NW, SUITE 600, WASHINGTON, DC 20036 USA SN 0021-972X EI 1945-7197 J9 J CLIN ENDOCR METAB JI J. Clin. Endocrinol. Metab. PD MAY PY 2014 VL 99 IS 5 BP E902 EP E907 DI 10.1210/jc.2013-3005 PG 6 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA AP8PB UT WOS:000342339800022 PM 24483153 ER PT J AU Roe, A Hillman, J Butts, S Smith, M Rader, D Playford, M Mehta, NN Dokras, A AF Roe, Andrea Hillman, Jennifer Butts, Samantha Smith, Mathew Rader, Daniel Playford, Martin Mehta, Nehal N. Dokras, Anuja TI Decreased Cholesterol Efflux Capacity and Atherogenic Lipid Profile in Young Women With PCOS SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article ID POLYCYSTIC-OVARY-SYNDROME; HIGH-DENSITY-LIPOPROTEIN; CARDIOVASCULAR-DISEASE; METABOLIC SYNDROME; PARTICLE-SIZE; RISK; DYSLIPIDEMIA; HEART; MANAGEMENT; TRANSPORT AB Context: Women with polycystic ovary syndrome (PCOS) have a high prevalence of cardiovascular disease (CVD) risk factors including dyslipidemia. Lipoproteins are heterogeneous, and measurement of serum lipids provides only the size of the pool and does not predict their function or composition. Recently, high-density lipoprotein cholesterol (HDL-C) function, as determined by cholesterol efflux capacity from macrophages, has been shown to be an independent predictor of subclinical CVD. Objective: The aim of the study was to comprehensively evaluate lipoprotein profile including lipid particle size and number and cholesterol efflux capacity in PCOS to better define CVD risk. Design and Setting: A case control study was performed at an academic PCOS center. Patients: Women with PCOS (n = 124) and geographically matched controls (n = 67) were included in the study. Main Outcome Measures: The primary outcome was to measure HDL-C efflux capacity by an ex vivo system involving the incubation of macrophages with apolipoprotein (Apo) B-depleted serum from subjects, and the secondary outcome was to measure lipid particle size and number using nuclear magnetic resonance spectroscopy. Results: Women with PCOS had significantly higher body mass index and blood pressure but similar HDL-C and low-density lipoprotein cholesterol levels compared to controls. The mean ApoA1 levels were lower, and the ApoB/ApoA1 ratio was higher in PCOS subjects compared to controls (P < .01). There were no differences in ApoB levels. Women with PCOS had an 7% decrease in normalized cholesterol efflux capacity compared to controls (P < .003). Cholesterol efflux capacity in PCOS correlated with body mass index, ApoA1, HDL-C, and the presence of metabolic syndrome. In a multivariable regression model, PCOS was significantly associated with diminished cholesterol efflux. PCOS was also associated with an atherogenic profile including an increase in large very low-density lipoprotein particles, very low-density lipoprotein (VLDL) size, and small low-density lipoprotein cholesterol particles (P < .01). Conclusions: Our novel findings of decreased cholesterol efflux and an atherogenic lipid particle number and size pattern in women with PCOS, independent of obesity, further substantiate the increased risk of CVD in this population. C1 [Roe, Andrea; Hillman, Jennifer; Butts, Samantha; Smith, Mathew; Dokras, Anuja] Univ Penn, Dept Obstet & Gynecol, Div Reprod Endocrinol, Philadelphia, PA 19104 USA. [Rader, Daniel] Univ Penn, Translat Res Ctr 11 125, Div Translat Med & Human Genet, Philadelphia, PA 19104 USA. [Playford, Martin; Mehta, Nehal N.] NHLBI, Sect Inflammat & Cardiometabol Dis, Bethesda, MD 20892 USA. RP Dokras, A (reprint author), Univ Penn, Dept Obstet & Gynecol, Div Reprod Endocrinol, 3701 Market St,Suite 800, Philadelphia, PA 19104 USA. EM adokras@obgyn.upenn.edu FU National Institutes of Health [DK19525]; FOCUS medical student fellowship awards at the University of Pennsylvania FX This work was funded by National Institutes of Health Grant DK19525 to the Diabetes Research Center RIA Biomarkers Core at the University of Pennsylvania. A.R. and J.H. were recipients of FOCUS medical student fellowship awards at the University of Pennsylvania. NR 31 TC 15 Z9 15 U1 0 U2 0 PU ENDOCRINE SOC PI WASHINGTON PA 2055 L ST NW, SUITE 600, WASHINGTON, DC 20036 USA SN 0021-972X EI 1945-7197 J9 J CLIN ENDOCR METAB JI J. Clin. Endocrinol. Metab. PD MAY PY 2014 VL 99 IS 5 BP E841 EP E847 DI 10.1210/jc.2013-3918 PG 7 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA AP8PB UT WOS:000342339800012 PM 24512495 ER PT J AU Klenke, U Taylor-Burds, C Wray, S AF Klenke, Ulrike Taylor-Burds, Carol Wray, Susan TI Metabolic Influences on Reproduction: Adiponectin Attenuates GnRH Neuronal Activity in Female Mice SO ENDOCRINOLOGY LA English DT Article ID ACTIVATED PROTEIN-KINASE; ENDOTHELIAL-CELLS; LHRH NEURONS; PARAVENTRICULAR NUCLEUS; CALCIUM OSCILLATOR; HORMONE-1 NEURONS; EXPLANT CULTURES; GENE-EXPRESSION; PITUITARY-GLAND; ENERGY-BALANCE AB Metabolic dysfunctions are often linked to reproductive abnormalities. Adiponectin (ADP), a peripheral hormone secreted by white adipose tissue, is important in energy homeostasis and appetite regulation. GnRH neurons are integral components of the reproductive axis, controlling synthesis, and release of gonadotropins. This report examined whether ADP can directly act on GnRH neurons. Double-label immunofluorescence on brain sections from adult female revealed that a subpopulation of GnRH neurons express ADP receptor (AdipoR) 2. GnRH/AdipoR2+ cells were distributed throughout the forebrain. To determine the influence of ADP on GnRH neuronal activity and the signal transduction pathway of AdipoR2, GnRH neurons maintained in explants were assayed using whole-cell patch clamping and calcium imaging. This mouse model system circumvents the dispersed distribution of GnRH neurons within the forebrain, making analysis of large numbers of GnRH cells possible. Single-cell PCR analysis and immunocytochemistry confirmed the presence of AdipoR2 in GnRH neurons in explants. Functional analysis revealed 20% of the total GnRH population responded to ADP, exhibiting hyperpolarization or decreased calcium oscillations. Perturbation studies revealed that ADP activates AMP kinase via the protein kinase C zeta/liver kinase B1 pathway. The modulation of GnRH neuronal activity by ADP demonstrated in this report directly links energy balance to neurons controlling reproduction. C1 [Klenke, Ulrike; Taylor-Burds, Carol; Wray, Susan] NINDS, Cellular & Dev Neurobiol Sect, NIH, Bethesda, MD 20892 USA. RP Wray, S (reprint author), 35 Lincoln Dr, Bethesda, MD 20892 USA. EM wrays@ninds.nih.gov OI wray, susan/0000-0001-7670-3915 FU Intramural Research Program of the National Institutes of Health, National Institute of Neurological Disorder and Stroke [NS002824-23] FX This work was supported by the Intramural Research Program of the National Institutes of Health, National Institute of Neurological Disorder and Stroke Grant NS002824-23. NR 76 TC 8 Z9 8 U1 0 U2 6 PU ENDOCRINE SOC PI WASHINGTON PA 2055 L ST NW, SUITE 600, WASHINGTON, DC 20036 USA SN 0013-7227 EI 1945-7170 J9 ENDOCRINOLOGY JI Endocrinology PD MAY PY 2014 VL 155 IS 5 BP 1851 EP 1863 DI 10.1210/en.2013-1677 PG 13 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA AP8PY UT WOS:000342342200027 PM 24564393 ER PT J AU Valdiserri, R Khalsa, J Dan, C Holmberg, S Zibbell, J Holtzman, D Lubran, R Compton, W AF Valdiserri, Ronald Khalsa, Jag Dan, Corinna Holmberg, Scott Zibbell, Jon Holtzman, Deborah Lubran, Robert Compton, Wilson TI Confronting the Emerging Epidemic of HCV Infection Among Young Injection Drug Users SO AMERICAN JOURNAL OF PUBLIC HEALTH LA English DT Article ID HEPATITIS-C VIRUS; UNITED-STATES; USE DISORDERS; NEW-YORK; RISK; ABUSE; ADOLESCENTS; HEALTH; ADULTS; HIV AB Hepatitis C virus infection is a significant public health problem in the United States and an important cause of morbidity and mortality. Recent reports document HCV infection increases among young injection drug users in several US regions, associated with America's prescription opioid abuse epidemic. Incident HCV infection increases among young injectors who have recently transitioned from oral opioid abuse present an important public health challenge requiring a comprehensive, community-based response. We summarize recommendations from a 2013 Office of HIV/AIDS and Infectious Disease Policy convening of experts in epidemiology, behavioral science, drug prevention and treatment, and other research; community service providers; and federal, state, and local government representatives. Their observations highlight gaps in our surveillance, program, and research portfolios and advocate a syndemic approach to this emerging public health problem. C1 [Valdiserri, Ronald; Dan, Corinna] US Dept HHS, Off HIV AIDS & Infect Dis Policy, Washington, DC 20201 USA. [Khalsa, Jag; Compton, Wilson] NIDA, Bethesda, MD 20892 USA. [Lubran, Robert] Subst Abuse & Mental Hlth Serv Adm, Rockville, MD USA. [Holmberg, Scott; Zibbell, Jon; Holtzman, Deborah] Ctr Dis Control & Prevent, Atlanta, GA USA. RP Valdiserri, R (reprint author), US Dept HHS, 200 Independence Ave SW,Room 443-H, Washington, DC 20201 USA. EM ron.valdiserri@hhs.gov OI Lubran, Robert/0000-0003-1235-5207 NR 51 TC 28 Z9 28 U1 3 U2 7 PU AMER PUBLIC HEALTH ASSOC INC PI WASHINGTON PA 800 I STREET, NW, WASHINGTON, DC 20001-3710 USA SN 0090-0036 EI 1541-0048 J9 AM J PUBLIC HEALTH JI Am. J. Public Health PD MAY PY 2014 VL 104 IS 5 BP 816 EP 821 DI 10.2105/AJPH.2013.301812 PG 6 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA AP0XU UT WOS:000341790600022 PM 24625174 ER PT J AU Choi, CI Yoon, SP Choi, JM Kim, SS Lee, YD Birnbaumer, L Suh-Kim, H AF Choi, Chan-Il Yoon, Sang-Phil Choi, Jung-Mi Kim, Sung-Soo Lee, Young-Don Birnbaumer, Lutz Suh-Kim, Haeyoung TI Simultaneous deletion of floxed genes mediated by CaMKII alpha-Cre in the brain and in male germ cells: application to conditional and conventional disruption of Go alpha SO EXPERIMENTAL AND MOLECULAR MEDICINE LA English DT Article DE brain; Cre; CaMKII alpha; Gnao; testis ID CALMODULIN KINASE-II; TRANSGENE EXPRESSION; MOUSE-BRAIN; MICE; RECOMBINATION; MUTAGENESIS; DEFICIENT; ALLELES; CORTEX; TRKB AB The Cre/LoxP system is a well-established approach to spatially and temporally control genetic inactivation. The calcium/calmodulin-dependent protein kinase II alpha subunit (CaMKII alpha) promoter limits expression to specific regions of the forebrain and thus has been utilized for the brain-specific inactivation of the genes. Here, we show that CaMKII alpha-Cre can be utilized for simultaneous inactivation of genes in the adult brain and in male germ cells. Double transgenic Rosa26(+/stop-lacZ)::CaMKII alpha-Cre(+/Cre) mice generated by crossing CaMKII alpha-Cre(+/Cre) mice with floxed ROSA26 lacZ reporter (Rosa26(+/stop-lacZ)) mice exhibited lacZ expression in the brain and testis. When these mice were mated to wild-type females, about 27% of the offspring were whole body blue by X-gal staining without inheriting the Cre transgene. These results indicate that recombination can occur in the germ cells of male Rosa26(+/stop-lacZ):: CaMKII alpha-Cre(+/Cre) mice. Similarly, when double transgenic Gnao(+/f)::CaMKII alpha-Cre(+/Cre) mice carrying a floxed Go-alpha gene (Gnao(f/f)) were backcrossed to wild-type females, approximately 22% of the offspring carried the disrupted allele (Gnao(Delta)) without inheriting the Cre transgene. The Gnao(Delta/Delta) mice closely resembled conventional Go-alpha knockout mice (Gnao(-/-)) with respect to impairment of their behavior. Thus, we conclude that CaMKII alpha-Cre mice afford recombination for both tissue-and time-controlled inactivation of floxed target genes in the brain and for their permanent disruption. This work also emphasizes that extra caution should be exercised in utilizing CaMKII alpha-Cre mice as breeding pairs. C1 [Choi, Chan-Il; Yoon, Sang-Phil; Choi, Jung-Mi; Kim, Sung-Soo; Lee, Young-Don; Suh-Kim, Haeyoung] Ajou Univ, Sch Med, Dept Anat, Suwon 443721, South Korea. [Choi, Chan-Il; Yoon, Sang-Phil; Choi, Jung-Mi; Suh-Kim, Haeyoung] Ajou Univ, Sch Med, Neurosci Grad Program, Suwon 443721, South Korea. [Choi, Chan-Il; Yoon, Sang-Phil; Choi, Jung-Mi; Suh-Kim, Haeyoung] Ajou Univ, Sch Med, Div Cell Transformat & Restorat BK21, Suwon 443721, South Korea. [Kim, Sung-Soo; Lee, Young-Don] Ajou Univ, Sch Med, Ctr Cell Death Regulating Biodrug, Suwon 443721, South Korea. [Lee, Young-Don] Ajou Univ, Dept Mol Sci & Technol, Suwon 443721, South Korea. [Birnbaumer, Lutz] NIEHS, NIH, Dept Hlth & Human Serv, Res Triangle Pk, NC 27709 USA. RP Suh-Kim, H (reprint author), Ajou Univ, Sch Med, Dept Anat, San 5 Wonchon Dong, Suwon 443721, South Korea. EM hysuh@ajou.ac.kr FU NIH, NIEHS [Z01-ES101643]; Korea Healthcare technology RD Project [HI10C14110100, HI10C14110300]; Bio & Medical Technology Development Program of the Korean National Research Foundation [NRF-2010-0020406] FX This study was supported in part by the Intramural research Program of the NIH, NIEHS (project Z01-ES101643 to LB); by the Korea Healthcare technology R&D Project (HI10C14110100 to HS-K & HI10C14110300 to S-SK) and the Bio & Medical Technology Development Program of the Korean National Research Foundation (NRF-2010-0020406 to HS-K). NR 33 TC 4 Z9 4 U1 1 U2 7 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1226-3613 EI 2092-6413 J9 EXP MOL MED JI Exp. Mol. Med. PD MAY PY 2014 VL 46 AR e93 DI 10.1038/emm.2014.14 PG 8 WC Biochemistry & Molecular Biology; Medicine, Research & Experimental SC Biochemistry & Molecular Biology; Research & Experimental Medicine GA AP7WY UT WOS:000342290100001 PM 24787734 ER EF